PMID- 8340526 TI - The health of our children and their use of medical services. PMID- 8340527 TI - Increasing enrollment of very young children in educational programs. PMID- 8340528 TI - Increased acidity in frozen fruit juices and dental implications. PMID- 8340529 TI - Autoantibodies in scleroderma. AB - Autoantibodies directed against nuclear, nucleolar, and a number of cytoplasmic components are described in the sera of scleroderma patients. Early studies of autoantibodies that relied on cryopreserved sections of rodent organ substrates showed that approximately 50% of scleroderma patients had anti-nuclear antibodies (ANA). More recent studies that have used tissue culture cell substrates have shown that up to 98% of scleroderma patients have a positive ANA. In all of these studies, the presence of different patterns of staining have suggested that scleroderma sera reacted with a variety of intracellular antigens. The use of molecular and immunochemical techniques has now shown that over 20 intracellular autoantigens are targets of autoantibodies in scleroderma sera. Clinical studies have shown that these autoantibodies are important diagnostic and prognostic markers in scleroderma. In the future, autoantibody testing may be used to monitor the patient's response to immunological therapies. PMID- 8340530 TI - Clinical criteria for differentiating between recessive and dominant forms of dystrophic epidermolysis bullosa, elaborated from an analysis of 119 cases. AB - We attempted to establish clinical criteria which differentiated between recessive dystrophic epidermolysis bullosa (RDEB) and dominant DEB (DDEB), since these two groups show prominent differences in prognosis, genetic recurrence risk and response to some types of treatment. The total of 119 cases examined consisted of our own 9 cases (2 of RDEB and 7 of DDEB) and 110 cases (26 of RDEB and 84 of DDEB) collected from the medical literature. They were analyzed by calculating the sensitivity and specificity of ten clinical features. We concluded that, syndactyly, presence of complications, dental lesions, remission less course, and oral lesions are strongly indicative of RDEB (more than 70% specific). Intractable skin ulcer is suggestive of RDEB (more than 55% specific). Nail lesions, scar and atrophy, milia and pigmentation are not helpful in the differentiation because of their commonality. The proposed criteria are simple, reliable, and practical, providing us with a useful tool for differentiation of RDEB and DDEB in daily practice. PMID- 8340531 TI - An analysis of 24 patients with IgA deposition at the BMZ. AB - A study of 24 patients with IgA deposition at the BMZ of the skin showed that five conditions could be recognized: 1) linear IgA bullous dermatosis in adults (LAD, 7 cases); 2) linear IgA and IgG bullous dermatosis in adults (LAGD, 10 cases); 3) chronic bullous disease of childhood (CBDC, 3 cases); 4) dermatitis herpetiformis (DH, 1 case), and 5) systemic lupus erythematosus (SLE, 3 cases). Histopathologically, 5 of 7 patients with LAD were similar to the DH group, but 7 of 10 patients with LAGD were similar to the BP group. Half the patients with LAD and LAGD had oral lesions, and most of them had excellent responses to dapsone and Tripterygium Wilfordii, but the patients with CBDC did not respond to these treatments. In the patients with LAD and LAGD, the positivity rates of IgA anti BMZ antibodies examined by indirect immunofluorescence (IIF) on intact skin and NaCl split skin were 41% and 64%, respectively. The heterogeneity of the histopathologic pictures of LAD and LAGD, the incidence of DH, and the value of using NaCl split skin for IIF are discussed. PMID- 8340532 TI - Cutaneous reactions induced by calcium channel blocker: high frequency of psoriasiform eruptions. AB - Fifteen cases with cutaneous reactions to calcium channel blockers (Ca antagonist), dihydropiridine (including nicardipine, nifedipine, nisoldipine), verapamil, and diltiazem are reported. The patients from Yokohama City University Hospital and affiliated hospitals included 4 males and 11 females with cardiovascular diseases. Their average age was 64.7 (54 to 82) years. They had been taking Ca-antagonists for an average of 95 days (7 days to 10 years) before they developed dermatitis. The frequency of reactions to Ca-antagonists was high with diltiazem (5/16:31.25%) and dihydropyridine (7/16:43.75%), including nifedipine (4/7), nisoldipine (1/7), and nicardipine (2/7). Stevens-Johnson syndrome (MCOS) was associated only with verapamil. A notable type of eruption was the psoriasiform type, including exacerbation of psoriasis, which was resolved or easily controlled after discontinuation of the drug. Provocation tests verified the Ca-antagonist as the cause in 7 cases of psoriasiform eruption. The frequency of positive patch tests to Ca-antagonists was low except for diltiazem. Patch tests with diltiazem showed positive reactions in 54% (7 of 13 patients), based on our experience and papers published in Japan. Ca antagonists are occasional causes of a wide spectrum of cutaneous reactions and should also be considered as causative factors in patients who develop psoriasiform eruptions or in patients whose psoriasis is exacerbated while using these drugs. PMID- 8340533 TI - A correlation between carotenemia and biliary dyskinesia. AB - The interrelationship between carotenemia and biliary dyskinesia was studied in eighty-two biliary dyskinesia patients and twenty-seven normal subjects. Incidence of serum carotene levels of more than 300 micrograms/dl was more frequent in biliary dyskinesia patients without liver damage or hyperlipemia. Among the carotenemia patients, no dietary cases were found, but metabolic and hyperlipemic ones were observed. Significant relationships were found between gall bladder contraction rate and the levels of serum carotene, vitamin A, and lipids in metabolic carotenemia. A close relationship between metabolic carotenemia and biliary dyskinesia was strongly suggested. PMID- 8340534 TI - Association of generalized granuloma annulare with autoantibodies. AB - Granuloma annulare is a degenerative disease of the skin histopathologically characterized by focal degeneration of collagen with a surrounding infiltrate of lymphoid cells, histiocytic cells, and multinucleated giant cells. Immunological abnormalities such as delayed-type hypersensitivity and vasculitic origin are suspected in the pathogenesis. We describe three patients with generalized granuloma annulare, in whom autoantibodies, including antinuclear antibody, antithyroid stimulating hormone receptor antibody, and immune complex, were detected. PMID- 8340535 TI - A case of cutaneous B-cell lymphoma with a storiform stromal reaction. AB - A case of cutaneous B-cell lymphoma is described. The patient was treated only by surgical excision of the skin tumors five times during a period of about two years from February of 1984 to October of 1986. After the last surgical excision, a continuous disease-free period was achieved. Biopsy samples showed dense lymphocytic infiltrations with discrete masses in the dermis and subcutis; one of them showed a storiform pattern. At the time, the infiltrating cells were composed of medium and large lymphoid cells and spindle-shaped cells. The medium and large lymphoid cells were positive for CD20, CD22 and HLA-DR and negative for CD3, CD4, CD5, CD8, CD43, and kappa and lambda light chain. The spindle-shaped cells were negative for CD20, CD43, kappa and lambda light chain, lysozyme, and S 100 protein. PMID- 8340536 TI - A case of necrobiosis lipoidica treated with systemic corticosteroid. AB - A 43-year-old woman had asymptomatic eruptions on the anterior sides of both legs for 5 years. Biopsy specimens revealed the typical findings of necrobiosis lipoidica. An immunofluorescence study demonstrated no deposits of immunoglobulins, complement, or fibrinogen in vessel walls. Immunohistochemical staining revealed CD4 positive lymphocytes dominating in the lesion and strong expression of ICAM-1 on the endothelial cells, giant cells, lymphocytes and dermal fibroblasts in the lesion. The eruptions resolved remarkably with oral corticosteroid therapy. PMID- 8340537 TI - Familial cases of psoriasis vulgaris and pustulosis palmaris et plantaris. AB - Two familial cases of psoriasis vulgaris and pustulosis palmaris et plantaris and their HLA types were examined. Our cases suggest a close genetic relationship between these two diseases. PMID- 8340538 TI - Papillary tubular adenoma of the skin. AB - A case of papillary tubular adenoma of the skin in a 31-year-old black man is reported. This lesion is also termed papillary eccrine adenoma, and it commonly occurs in the extremities. PMID- 8340539 TI - Effects of ultraviolet radiation on the alloreactivity of splenic T cells. PMID- 8340540 TI - Might does not equal right. PMID- 8340541 TI - Taking responsibility. PMID- 8340542 TI - Why no dental dam? PMID- 8340543 TI - Delegating duties. PMID- 8340544 TI - A timely report. PMID- 8340545 TI - Implant dentistry: where are we now? AB - Dental implants can dramatically change a patient's self-esteem and quality of life. But too few people receive implants because of the cost and lack of education in this growing field. More training, systems standardization and practice guidelines will improve implant treatment availability. PMID- 8340546 TI - The developing market for dental implants. AB - A survey of U.S. dentists showed that dental implant use increased 73 percent between 1986 and 1990. More than half of all implants are placed by oral and maxillofacial surgeons. Most dentists who place implants are not affiliated with professional implant organizations; training for implant placement varies widely. PMID- 8340547 TI - Evaluating CAD-CAM generated ceramic veneers. AB - As the CAD-CAM technique has been expanded to include porcelain facings, of particular interest is adapting the veneer to the prepared surface. In a comparison of the gap dimension of CAD-CAM generated veneers to those produced in the laboratory, no statistically significant differences were detected. PMID- 8340548 TI - Feeding patterns, water sources and fluoride exposures of infants and 1-year olds. AB - Concern about dental fluorosis prompted this study of feeding habits, water sources and fluoride exposures of about 100 children from birth to 18 months. Toothbrushing habits and dentrifice use, both at home and during child care, must be considered to estimate fluoride exposures and ingestion. PMID- 8340549 TI - The plaque fighters: choosing a weapon. AB - In recent years new head shapes and angles, bristle lengths and designs, have flooded the toothbrush market. Are these truly innovations or just gimmicks? Several comparative studies are reviewed. PMID- 8340550 TI - Possibility of cross-contamination between dental patients by means of the saliva ejector. AB - Concern about cross-contamination between dental patients prompted investigation of current suctioning practices. The possibility of the suck-back phenomenon and the presence of oral bacteria in vacuum lines were studied, and dental offices were surveyed concerning the use and disinfection of suction equipment. PMID- 8340551 TI - Guided tissue regeneration in oral reconstruction: surgical and restorative applications. PMID- 8340552 TI - Hastening the enamel microabrasion procedure eliminating defects, cutting treatment time. AB - Two cases illustrate the technique of treating enamel discoloration and decalcification by beginning with bur cutting and completing with microabrasion compound. This eliminates texture defects caused by bur cutting and reduces treatment time. PMID- 8340553 TI - Keeping interocclusal records: how to solve a common problem. PMID- 8340554 TI - Surviving practice downturn: a case study in dental marketing. AB - Unexplained downturns can destroy a healthy practice. This report details the warning signs and offers a blueprint for keeping your practice on track. PMID- 8340555 TI - Comparison of adaptations and compliance to exercise training between middle-aged and older men. AB - OBJECTIVE: To compare the rate and magnitude of physiologic and psychologic adaptations to aerobic training between middle-age and older men, to assess their interest in continued participation (> 6 months) in a supervised high-intensity training program, and to evaluate the safety of high-intensity training for older people. DESIGN: Before-after intervention trial. SETTING: Medical center in a Midwestern metropolitan city. PARTICIPANTS: Thirteen middle-age (35-50 years) and 14 older (60-71 years) normal men. INTERVENTION: Subjects trained on treadmills and leg cycle ergometers for 40 minutes 3 times per week. The intensity was increased to 85% of peak heart rate (HR) within the first 3 weeks of training. MEASUREMENT: Peak oxygen consumption, HR at submaximal work rates, three psychological tests, and election to continue in the supervised program. RESULTS: At 6 months of training, peak oxygen consumption had increased by 12% and 11% in the middle-aged and older groups, respectively, with 86% and 100% of this increase occurring within the first 3 months. Both groups showed comparable decreases in HR at submaximal work rates after 3 months of training with no further significant change from 3 to 6 months. None of the psychologic parameters evaluated changed significantly with 3 or 6 months of training in either group. More of the older (71%) than middle-aged (45%) men elected to continue in the supervised program after 6 months. CONCLUSIONS: The results of this study involving small groups of carefully screened middle-aged and older men suggest that the time course and magnitude of physiologic adaptations to aerobic training are similar between age groups when the training regimen is the same. Neither age group showed alterations in psychologic parameters nor experienced orthopedic injuries with training. The older group showed greater interest in continued participation in a supervised exercise program. PMID- 8340556 TI - Characteristics and quality of prescribing by doctors practicing in nursing homes. AB - OBJECTIVES: To describe the professional characteristics of doctors practicing in nursing homes and to determine whether those characteristics correlate with quality of prescribing. DESIGN: A prospective, cohort study. PARTICIPANTS: 306 physicians practicing in 12 nursing homes in greater Los Angeles. MEASUREMENTS: We surveyed doctors about their age, sex, education, credentials, and NH practice. We also determined medication orders for a 1-month period and evaluated them using explicit criteria for appropriateness developed by an expert panel. RESULTS: We obtained data from 72% of MDs. Respondents had a mean age of 53 years (29-78) and were 94% male. Fifty-seven percent trained in internal medicine, 20% graduated outside the US or Canada, 67% were board certified in their declared specialty, and 5% had a certificate of added qualification in geriatrics (CAQ). Sixteen percent spent > 10% of their professional time in NHs, and 46% had NH practices that were > 20% Medicaid; most did not consult psychiatrists when prescribing psychoactive drugs. Forty percent of residents had at least one inappropriate prescription. The characteristics of doctors associated with the best prescribing quartile were female sex, CAQ, no board certification, and frequent consultation with psychiatrists. The characteristics of doctors in the most inappropriate quartile were older age, graduation from medical school before 1965, graduation from US medical school, small NH practice, and infrequent consultation with psychiatrists. CONCLUSIONS: Although the quality of prescribing in nursing homes is related to some physician characteristics, the relationships are not those most commonly stated. PMID- 8340557 TI - Disposition of intramuscular cefonicid in elderly patients. AB - OBJECTIVE: To examine the disposition of intramuscular (IM) cefonicid in elderly patients with bacterial pneumonia. DESIGN: Pharmacokinetic study. SETTING: A 620 bed university-affiliated long-term care institution with its own 39-bed acute care unit. PATIENTS: Nine consecutive elderly patients with bacterial pneumonia treated with IM cefonicid. MEASUREMENTS: Blood samples were collected on the seventh day of therapy over a 24-hour period and analyzed by high performance liquid chromatography. Pharmacokinetics parameters (volume of distribution, half life, and clearance) and protein binding were calculated. Clinical outcome of IM cefonicid therapy was also noted. RESULTS: The estimated creatinine clearance (CIcr) ranged from 32 to 145 mL/min. Peak cefonicid serum concentrations occurred at 0.5-1.5 hours, with a mean value of 118 +/- 41 micrograms/mL. Cefonicid concentrations declined monoexponentially to 57 +/- 16 micrograms/mL at 12 hours and 28 +/- 14 micrograms/mL at 24 hours. The mean apparent distribution volume was 0.2 +/- 0.07 L/kg, and the mean apparent total clearance was 15 +/- 12 mL/min. The half-life ranged from 3.1 to 38 hours. A linear correlation was noted between Clcr and cefonicid clearance (r = 0.99). CONCLUSIONS: Cefonicid absorption was variable among these patients, and the serum half-life was longer than previous values noted in younger patients with similar degree of renal dysfunction. Pharmacokinetic and clinical outcome data from our study group indicate the potential role of IM cefonicid in treating elderly patients with bacterial pneumonia. PMID- 8340558 TI - Screening elders for risk of hospital admission. AB - OBJECTIVE: To define a set of screening criteria that identifies elders who are at high risk for repeated hospital admission in the future. DESIGN: Longitudinal cohort study. Logistic regression analysis of data from half of the subjects was used to identify risk factors for repeated hospital admission. The ability of these risk factors to identify elders who are at high risk for repeated hospitalization in the future was then tested using data from the other half of the subjects. SETTING: United States. PARTICIPANTS: A subsample (n = 5876) of a multistage probability sample of all non-institutionalized U.S. civilians who were 70 years or older in 1984. MEASUREMENTS: At baseline (1984), elderly subjects were asked about their demographic, socioeconomic, medical, and functional characteristics and about their recent use of health services. Their subsequent hospital admissions and mortality were then monitored through the records of the Medicare program and the National Death Index (1985-88). RESULTS: Among the subjects in the first half of the sample, eight factors emerged as risk factors for repeated admission: older age, male sex, poor self-rated general health, availability of an informal caregiver, having ever had coronary artery disease, and having had, during the previous year, a hospital admission, more than six doctor visits, or diabetes. Based on the presence or absence of these factors in 1984, 7.2% of the subjects in the second half of the sample were estimated to have a high probability of repeated admission (Pra > or = 0.5) during 1985-1988. In comparison with subjects estimated to have a low risk (Pra < 0.5), this high-risk group's actual experiences during 1985-1988 included a higher cumulative incidence of repeated admission (41.8% vs 26.2%, P < 0.0001), a higher cumulative rate of mortality (44.2% vs 19.0%, P < 0.0001), more hospital days per person-year survived (5.2 vs 2.6), and higher hospital charges per person-year survived ($3731 vs $1841). CONCLUSION: Eight easily ascertained risk factors affect elders' probability of being hospitalized repeatedly within four years. In the future, brief surveys about the presence of these factors could be used to estimate elders' risk of future hospitalization and, thereby, to identify some of those who may derive the greatest benefit from interventions designed to avert the need for hospitalization. PMID- 8340559 TI - The effects of thiazide diuretics on calcium metabolism in the aged. AB - OBJECTIVE: To determine the effects of long-term use of the thiazide diuretic chlorthalidone on serum bone-related biochemical variables in older persons. DESIGN: Cross-sectional comparison. SETTING: Community-dwelling subjects who had participated in the Systolic Hypertension in the Elderly (SHEP) program. PARTICIPANTS: Sixty-six Caucasians (36 male and 30 female), age range 70 to 89 years, of whom 23 were taking a thiazide diuretic. MEASUREMENTS: 25 hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, calcitonin, and serum bioavailable testosterone. RESULTS: In both groups, there was a high prevalence of low 25 (OHD) levels (30%). Log 25OHD showed a significant inverse relationship to parathyroid hormone (r = .33, P < 0.05). Thiazide users had lower levels of osteocalcin (P < 0.05) and parathyroid hormone levels (P < 0.05) compared with non-thiazide users. Male thiazide users had decreased bioavailable testosterone levels compared with non-thiazide users (P < 0.05). Serum osteocalcin was significantly related to bioavailable testosterone in men not on thiazide (r = .43, P < 0.05). CONCLUSIONS: Hypovitaminosis D is a common finding in older individuals with associated elevations in parathyroid hormone. Parathyroid hormone and testosterone concentration (in men) are correlated with serum osteocalcin, a measure of osteoblastic activity. Long-term thiazide use alters these relationships and produces a biochemical profile suggestive of decreased bone formation. Reduced bioavailable testosterone may also play a role in these biochemical changes. PMID- 8340560 TI - Serum thyrotropin and thyroid hormone levels in elderly and middle-aged euthyroid persons. AB - OBJECTIVE: To determine whether serum thyrotropin (TSH) levels are altered in euthyroid older persons compared with middle-aged adults. DESIGN: Serum TSH and thyroid hormone levels were measured in a large group of older persons (> 70 years old, n = 216) and their middle-aged offspring (40-60 years old, n = 211) after excluding those with clinical or historical evidence of thyroid disease or abnormal thyroid function. MEASUREMENTS: Serum TSH, thyroxine (T4), free T4 index, estimated free T4, triiodothyronine (T3), estimated free T3, and ferritin levels were measured on the Abbott IMx instrument. Peroxidase and thyroglobulin antibodies were measured by radioimmunoassay using Kronus kits. MAIN RESULTS: Overall, serum TSH showed a log-normal distribution. The geometric mean TSH (mU/L) and 95% confidence limits in the older persons, 1.24 (0.29-5.4), did not differ significantly from that in the middle-aged, 1.45 (0.54-3.9). The mean TSH in the 264 women, 1.37 (0.34-5.5), was similar to that of the 163 men, 1.30 (0.48 3.5). The mean TSH in older women, 1.21 (0.22-6.6), was slightly but significantly lower than that in middle-aged women, 1.52 (0.55-4.2). However, when euthyroid women with positive antibodies were excluded, this difference was not significant. Four of the 123 older women had TSH < 0.1 mU/L, but none of the men or middle-aged women had a suppressed serum TSH. The mean TSH in older men, 1.28 (0.43-3.8), was similar to that in middle-aged men, 1.32 (0.55-3.2). Free T4 was slightly higher in older women than middle-aged women. There were no significant correlations between TSH and any thyroid hormone level. Serum ferritin, measured as a potential marker for the action of thyroid hormone, did not correlate with any measure of thyroid function. At least one antibody level was > 10 U/mL in 14.6% of older women, 15.6% of middle-aged women, 4.3% of older men, and no middle-aged men. When those with milder elevations of antibody levels were included (at least one level > 1 U/mL), the prevalence was 32% of older women, 43.3% of middle-aged women, 15% of older men, and 11.4% of middle-aged men. CONCLUSIONS: Euthyroid older persons have about the same levels of serum TSH as younger ones, although older euthyroid women have a slightly lower serum TSH than middle-aged women. We recommend that the normal range of serum TSH in the elderly be considered to be the same as that in healthy middle-aged subjects. PMID- 8340561 TI - Alleviation of sleep maintenance insomnia with timed exposure to bright light. AB - OBJECTIVE: Half of the population over 65 suffers from chronic sleep disturbance. As a consequence, almost 40% of hypnotic medications are prescribed to people over age 60. Yet, hypnotics are often of little benefit in this population. As such, an effective non-drug alternative could prove important in the management of age-related sleep maintenance insomnia. The current study sought to evaluate the efficacy of bright light exposure in the treatment of sleep maintenance insomnia. DESIGN: Following baseline sleep and circadian rhythms assessment, subjects with sleep-maintenance insomnia were treated with timed exposure to either bright white light or dim red light for 12 consecutive days. Sleep and circadian rhythms recordings were subsequently obtained and measures of sleep quality were compared to assess efficacy of the treatments. SETTING: Baseline and post-treatment sleep and circadian rhythms assessments took place in the Laboratory of Human Chronobiology, Department of Psychiatry, Cornell University Medical College. The treatment phase of the study was conducted in participants' homes. PARTICIPANTS: Sixteen men and women between the ages of 62 and 81 years were studied. All subjects were free of hypnotic medication, and all had experienced sleep disturbance for at least 1 year prior to entering the study. RESULTS: Exposure to bright light resulted in substantial changes in sleep quality. Waking time within sleep was reduced by an hour, and sleep efficiency improved from 77.5% to 90%, without altering time spent in bed. Increased sleep time was in the form of Stage 2 sleep, REM sleep, and slow wave sleep. The effects were remarkably consistent across subjects. CONCLUSIONS: The findings demonstrate the effectiveness of timed exposure to bright light in the treatment of age-related sleep maintenance insomnia. With further refinement of treatment regimens, this non-drug intervention may prove useful in a large proportion of sleep disturbed elderly. PMID- 8340562 TI - Nocturnal activity and immobility across aging (50-98 years) in healthy persons. AB - OBJECTIVE: To measure the influence of age on measures of nocturnal activity and immobility in 100 healthy subjects aged 50 to 98 years. DESIGN: Cross-sectional study. SETTING: Urban population in Leiden. Recordings were performed at home while the subjects maintained their habitual 24-hour pattern of activities. PARTICIPANTS: 100 subjects without a history of major medical disorders and a normal neurological examination and performance-oriented assessment of gait (Tinetti). MEASUREMENTS: Motor activity was recorded during six successive nights with a wrist-worn activity monitor. The occurrence of supra-threshold motor activity was recorded over 15-second epochs. A questionnaire was used to evaluate sleep habits and the occurrence of sleep disturbances. Four mean measures reflecting activity or immobility during the nocturnal period were calculated for each subject. RESULTS: Only one out of four measures, (ie, the nocturnal proportion of time with movement, increased with age for females. For males, no age effects emerged. The mean duration of nocturnal immobility periods was higher in females than in males. Also, for females, the use of hypnotics increased with successive decades. Sex and the use of hypnotics were significantly related to the mean duration of immobility periods. CONCLUSION: If care is taken not to confound aging with illness, measures of nocturnal activity and immobility reveal only marginal effects of aging. PMID- 8340563 TI - Poisoning in the elderly: characterization of exposures reported to a poison control center. AB - OBJECTIVE: To determine the incidence of poison center calls involving the elderly, characterize these poisonings, and compare them with poisonings that occur in people younger than 60 years of age. DESIGN: Concurrent, observational survey. SETTING: The Virginia Poison Center in Richmond, Virginia. PARTICIPANTS: All persons 60 years of age and older who were involved in a poison exposure reported to the Virginia Poison Center from October 1, 1991 through March 31, 1992. MEASUREMENTS: Incidence, type, route, location, management site, medical outcome of exposures and reasons for these exposures. RESULTS: Exposures in persons 60 years of age and older accounted for 2.3% of all poison center calls during the 6-month study period. These calls were most likely to involve women who unintentionally ingested extra doses of medications. The majority of these exposures occurred in the home and resulted in either no effect or minor effects. For those exposures that necessitated an emergency room visit, elderly persons were more likely to be admitted to the hospital than younger persons (P < 0.05). CONCLUSIONS: The majority of poisonings that occur in persons 60 years of age and older are unintentional and may be amenable to poison prevention education. PMID- 8340564 TI - Hospital resources used to treat the injured elderly at North Carolina trauma centers. AB - OBJECTIVE: The purpose of this paper is to compare the hospital resources used by elderly, adult, and pediatric patients treated in hospitals reporting to the North Carolina Trauma Registry (NCTR). DESIGN: We analyzed data on all patients entered into the NCTR from 1 January 1988 to 31 December 1990. SETTING: The NCTR is a statewide registry of all trauma patients admitted for at least 24 hours or dead on arrival at the eight Level I and II trauma center hospitals in North Carolina. PATIENTS: The total number of patients included in the study was 21,214; elderly adults included those age 65 and older (n = 2808), adults included those 15 to 64 years old (n = 15,776), and pediatric patients included those 0 to 14 years old (n = 2630). MAIN OUTCOME MEASURES: We examined hospital resources using three measures: overall length of hospital stay in days, intensive care unit (ICU) length of stay in days for those admitted to the ICU, and total hospital charges billed during the hospitalization. RESULTS: Controlling for injury severity, we found that elderly adults had longer mean hospital and ICU lengths of stay and higher mean hospital charges than adults or children. Whereas only 22% of injuries to elderly adults were transportation related, transportation injuries generated 38% of their hospital charges. Sixty eight percent of their injuries were caused by falls, generating total hospital charges of $17.6 million, an average of 15 days in hospital stay and 9 days in ICU stay. CONCLUSION: A 10% reduction in both transportation injuries and falls among the elderly could save $3.5 million in this population over 3 years. PMID- 8340565 TI - Aggressive behaviors among the institutionalized elderly. AB - OBJECTIVE: To describe the incidence and characteristics of aggressive behaviors in a group of institutionalized elderly. DESIGN: Retrospective survey. SETTING: 350-bed, urban skilled nursing facility. PATIENTS: All nursing home residents who had an incident report completed after an aggressive behavior. MEASUREMENTS: Examination of all incident reports of aggressive behavior for 1 year. RESULTS: There were 94 reports of aggressive behaviors. Twenty-nine residents exhibited one aggressive behavior, 12 residents two, and six residents exhibited three or more aggressive behaviors. These six residents accounted for 44% of all events. The incidence of aggressive behavior was 0.27 per resident per year for the entire facility; on the Alzheimer's unit the incidence was 0.75 per resident per year. Sixty-two percent of the victims of aggressive behavior were other nursing home residents, 37% were employees, and 1% were visitors. The charts of the six residents with three or more aggressive behaviors were reviewed. These residents received trials of multiple scheduled psychotropic medications, often exhibited several additional agitated behaviors around the time of the attack, were at risk for psychiatric hospitalizations during the study period, and often were noted to have underlying acute medical illnesses near the time of the attack. CONCLUSION: Approximately two aggressive behaviors per week occurred in a large nursing home. Residents and staff of Alzheimer's units have a higher risk of being victims of aggressive behavior. A small number of patients account for nearly half of the behaviors, even on the Alzheimer's unit. Aggressive behaviors may be clinical indicators of underlying acute medical illnesses. PMID- 8340566 TI - Acetazolamide and salicylate interaction in the elderly: a case report. PMID- 8340567 TI - Rhabdomyolysis in association with acute pressure sore. PMID- 8340568 TI - The older person and the emergency department. PMID- 8340569 TI - The American and Canadian consensus conferences on dementia: is there consensus? PMID- 8340570 TI - Age-related decline of influenza A virus-specific cytotoxic T lymphocyte activity. PMID- 8340571 TI - A more opportune description of the stages of aging. PMID- 8340572 TI - Characteristics of diabetic ketoacidosis in older patients. PMID- 8340573 TI - Health care for end-stage dementia. PMID- 8340574 TI - Physician-assisted suicide. PMID- 8340575 TI - Driving with cognitive impairment. PMID- 8340576 TI - Cobalamin deficiency in the elderly. PMID- 8340577 TI - Prehospital cardiac arrest survival and neurologic recovery. AB - Many studies of prehospital defibrillation have been conducted but the effects of airway intervention are unknown and neurologic follow-up has been incomplete. A non-randomized cohort prospective study was conducted to determine the effectiveness of defibrillation in prehospital cardiac arrest. Two ambulance companies in the study area developed a defibrillation protocol and they formed the experimental group. A subgroup of these patients received airway management with an esophageal obturator airway (EOA) or endotracheal intubation (ETT). The control group was composed of patients who suffered a prehospital cardiac arrest and did not receive prehospital defibrillation. All survivors were assessed for residual deficits using the Sickness Impact Profile (SIP) and the Dementia Rating Scale (DRS). A total of 221 patients were studied over a 32-month period. Both the experimental group (N = 161) and the control group (N = 60) were comparable with respect to age, sex distribution, and ambulance response time. Survival to hospital discharge was 2/60 (3.3%) in the control group and 12/161 (6.3%) in the experimental group. This difference is not statistically significant. Survival in the experimental group by airway management technique was basic airway support (3/76 3.9%), EOA (3/67 4.5%), and ETT (6/48 12.5%). The improved effect on survival by ETT management was statistically significant. Survivors had minor differences in memory, work, and recreation as compared to ischemic heart disease patients as measured by the SIP and DRS. No effect of defibrillation was found on survival to hospital discharge. However, endotracheal intubation improved survival in defibrillated patients. Survivors had a good functional outcome. PMID- 8340578 TI - Signs and symptoms of patients with brain tumors presenting to the emergency department. AB - This retrospective chart review was conducted to determine the presenting signs and symptoms of patients with primary brain tumors diagnosed in the emergency department. There were 101 patients (65 males and 36 females) identified with a hospital discharge diagnosis of primary brain tumor who were admitted through the emergency department. The presenting symptoms included headache (56 patients), altered mental status (51 patients), ataxia (41 patients), nausea or vomiting (37 patients), weakness (27 patients), speech deficits (21 patients), and sensory abnormalities (18 patients). The presenting signs included motor weakness (37 patients), ataxia (37 patients), papilledema (28 patients), cranial nerve palsies (26 patients), visual deficits (20 patients), and speech deficits (12 patients). The average age was 42.8 years, with a range of 3 days to 88 years. The majority of tumors were malignant astrocytomas. Tumor location was cortical in 68 patients, subcortical in 9 patients, and brainstem or cerebellum in 24 patients. In conclusion, patients of all ages may present to the emergency department with a variety of symptoms resulting from a primary brain tumor. Headache and altered mental status were common in our series of patients, but symptoms will depend on the size, location, and type of tumor. A complete neurologic examination is essential, including evaluation for papilledema. PMID- 8340579 TI - Retained foreign body: a fingernail fragment? AB - A 19-year-old female presented four and one-half months after an occupational injury from a punch-type machine. Exploration revealed a large fragment of her fingernail embedded in the fingerpad. Foreign bodies are commonly encountered in the practice of emergency medicine and failure to localize and remove them can result in significant morbidity. We present a case of a fingernail as a foreign body. Foreign bodies may be difficult to detect despite sophisticated imaging techniques. Although not visualized often, a radiolucent foreign body may be inferred from boney changes. A thorough history regarding mechanism of injury and resultant wound exploration are required. When an adequate wound examination using digital tourniquet control and proper precautions is performed, the majority of foreign bodies will be detected. PMID- 8340580 TI - Acute management of glycogen storage disease type Ia. AB - Rapid metabolic deterioration may occur in patients with some glycogen storage diseases (GSDs) regardless of presenting complaint. Hepatic, renal, and hemostatic abnormalities may also complicate diagnosis and treatment of trauma victims. We report the case of a man presenting with an epidural hematoma and a history of GSD type Ia. PMID- 8340581 TI - A 33-year-old white female with abdominal pain, nausea, vomiting and hypotension. AB - A thirty-three year old female presented to our emergency department complaining of severe abdominal pain, nausea, and vomiting. On physical examination she was hypotensive with a firm, tender abdomen, cervical motion tenderness and a diffuse erythematous rash. A surgical diagnosis of Acute Pelvic Inflammatory Disease was made during laparoscopy. Coagulant studies, liver function tests, culture results, and the desquamation of the patient's palms led to the additional diagnosis of Toxic Shock Syndrome. A literature search failed to reveal any similar cases of Pelvic Inflammatory Disease (PID) and Toxic Shock Syndrome (TSS) occurring concomitantly. Patients may present severely ill with either of these disease entities but potential for serious illness is greater when both of these syndromes occur in the same patient. We conclude that in patients with a similar presentation, the symptoms should not be attributed completely to PID without further investigation and consideration of a concomitant disease process including TSS. PMID- 8340582 TI - Misdiagnosis of bilateral ectopic pregnancies: a caveat about operator expertise in the use of transvaginal ultrasound. AB - Reported is the case of a 24-year-old female who presented to the Emergency Department complaining of lower abdominal pain and vaginal bleeding, whose initial transvaginal ultrasound was interpreted as showing a viable intrauterine pregnancy (IUP) of 8 weeks gestation. Repeat transvaginal ultrasound during a subsequent Emergency Department (ED) visit 3 days later revealed bilateral ectopic pregnancies of 6.5 weeks gestation. ED physicians should be familiar with the limitations of transvaginal sonography, and should be wary of early "intrauterine" pregnancies that are diagnosed ultrasonographically by inexperienced operators. PMID- 8340583 TI - Delayed cardiotoxicity following quinine overdose: a case report. AB - Quinine poisoning typically results in a constellation of non-life threatening symptoms which include tinnitus, deafness, nausea, vomiting, vision changes, headache, and hypotension. Cardiac conduction defects, dysrhythmias, and cardiovascular collapse have all been reported after overdose and generally occur within 8 hours of ingestion. We report a unique case of delayed cardiotoxicity following quinine ingestion. Toxicity included marked ventricular conduction abnormalities for which serum alkalinization appeared to be therapeutically beneficial, and torsades de pointes requiring overdrive pacing for termination. PMID- 8340584 TI - Benign course after massive ingestion of yohimbine. AB - Yohimbine is an alpha 2 adrenoreceptor antagonist occasionally used in the treatment of impotence. Overdose of this drug is uncommon. We describe a 62-year old male who ingested 100, 2.0 mg tablets whose only adverse effects were tachycardia, hypertension, and anxiety of brief duration. The limited experience to date suggests a benign course even after massive overdose. Observation would seem to be the management of choice. PMID- 8340585 TI - Reevaluation of plain radiographic findings in the diagnosis of aortic rupture: the role of inspiration and positioning on mediastinal width. AB - Despite the advent of newer imaging modalities, conventional radiography and clinical examination remain the primary screening method in evaluation of the mediastinum following blunt thoracic trauma. Mediastinal width (MW) is generally considered an important finding in assessing for aortic rupture. The degree of inspiration and patient positioning clearly affects MW, but is largely ignored in the literature. This study investigates the mediastinal widths of normal volunteers with differing degrees of inspiration and positioning, and compares them to radiographs of patients with known aortic ruptures. Mediastinal widths were obtained from chest radiographs of 16 patients with known aortic rupture, and from 50 volunteers using AP-inspiratory-supine, AP-expiratory-supine, and PA inspiratory-upright technique. Upper 95% confidence limits were obtained for normals. A statistically significant difference in MW of normals was found between inspiratory-supine, expiratory-supine, and upright-inspiratory techniques. Compared to the same degree of inspiration in normals, 12 of 16 patients with aortic rupture had a MW above the upper 95% confidence limits. It is concluded that mediastinal width in normals is significantly affected by the degree of inspiration and positioning. When comparing mediastinal widths for normals and ruptures, there was a significant difference in MW for most degrees of inspiration. As depth of inspiration increased, differences between MW in controls and rupture patients increased. We conclude that patient positioning and degree of inspiration are important factors in assessing the mediastinum, and every effort should thus be made to obtain an upright-inspiratory film if clinically feasible prior to declaring a mediastinum as abnormal. PMID- 8340586 TI - Recognition and management of sarcoidosis in the emergency department. AB - Sarcoidosis is a chronic granulomatous disease of uncertain etiology. It can affect essentially every organ system in the human body and its manifestations are protean. Sarcoidosis can present in the emergency department (ED) as de novo disease, as preexisting disease with acute exacerbations, or as chronic debilitation. The authors provide a review of the various manifestations of this disease with emphasis on ED presentation and evaluation. PMID- 8340587 TI - Electric shock, Part I: Physics and pathophysiology. AB - Electric shock causes injury and death through a variety of mechanisms. The proper treatment of a patient with electric shock depends upon the nature of the injuries sustained. The primary electric injuries to be expected depend in large part on the type of electric energy source, the amount and duration of current flow, and the parts of the body affected. Secondary injury can be caused by trauma associated with the electric accident such as falls and explosions. PMID- 8340588 TI - Austin Flint: on cardiac murmurs. AB - Austin Flint first ausculted the murmur associated with his name in 1859. Suspecting it to be of mitral origin, he identified it as occurring in aortic insufficiency three years later. Recent echocardiographic study has indicated that this murmur is produced by an aortic insufficiency jet colliding with the anterior mitral valve leaflet. Flint was among the first to recognize the importance of normal cardiac and respiratory sounds. He advocated routine auscultation on all patients, and had great influence in popularizing auscultation in American medicine. PMID- 8340589 TI - The role of emergency services in health care for the elderly: a review. AB - The hospital emergency department (ED) has become an important means of access to health care for the elderly. Inadequacies in the current health care system for the elderly are reflected in their high utilization rates of the ED, continuing questions about the appropriateness of elderly ED patients, differences in the ED care offered the elderly versus the young, and poor coordination of care to and from the ED. Evidence of potential misuse of emergency services exists for both the ED and the emergency medical transport (EMS) systems. The increasing number of nursing home patients sent to the ED with nonemergent problems further emphasizes inadequacies of primary care in the nursing home setting. Economic, legal, and ethical issues that have changed the way medicine is practiced in other settings are finally reaching the sector of emergency services. The current and future roles of emergency medicine services, and the impact these issues will have on the practice of emergency medicine, are discussed. PMID- 8340590 TI - Robert M. Berne, teacher, scientist, and inventor. PMID- 8340591 TI - Ethics and continuous quality improvement. PMID- 8340592 TI - Emergency department discharges against medical advice. PMID- 8340593 TI - Staph aureus sepsis following emergent nasal intubation. PMID- 8340594 TI - The English system. PMID- 8340595 TI - Akathisia causing suicide attempts in patients taking fluoxetine (Prozac) PMID- 8340596 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: neurology. AB - This is the twenty-first article in a continuing series of objectives to direct resident training in emergency medicine. Presented is a set of objectives with references for curriculum goals in neurology. Knowledge of neurology and clinical skills in diagnosing neurological illness is important in the practice of emergency medicine. Not all emergency residents have adequate exposure to the subspecialty of neurology. Many residents who have exposure to a neurology elective often spend only two weeks on the service. Therefore, a clear set of goals and objectives is essential for the resident to obtain a comprehensive knowledge of this complex specialty. PMID- 8340597 TI - Health policy and quality: an ethical dilemma. AB - Emergency medicine is on the front line of many important health issues, such as access for the poor and uninsured, the AIDS epidemic, and domestic violence. Virtually all key policy issues relating to emergency medicine deal with the concept of quality. During the 1970s, quality issues dealt with issues of value. Interest in quality is now vested in the tradeoff between cost containment activities and preserving access to health care. Key definitions of efficacy, effectiveness, and efficiency are provided. A policy approach to quality definition and assessment is suggested based upon the concepts of continuous quality improvement. The role of emergency physicians in health policy and the future of emergency medicine are discussed. PMID- 8340598 TI - Edlich's academical village. AB - Dr. Richard F. Edlich, Distinguished Professor of Plastic Surgery and Biomedical Engineering, recently received the Thomas Jefferson Award, the highest honor that can be bestowed upon a faculty member at the University of Virginia. Reflections of his "Academical Village" are presented to share ideas from the teaching environment he has created. PMID- 8340599 TI - The Canadian Association of Emergency Physicians (CAEP/ACMU). AB - The Canadian Association of Emergency Physicians is a diverse group of 500 practitioners providing emergency care to the ill and injured. The specialty section of the organization represents Royal College certificants and is 120 strong. The Association, with headquarters in Ottawa, has a major interest in the continuing education of its members, policy development and the improvement of emergency health care in the country. PMID- 8340600 TI - New challenges in hepatic fibrosis. AB - Treatment of hepatic fibrosis by simple and inexpensive therapies is a new challenge for the near future. Hepatic fibrosis which may lead to cirrhosis, is indeed associated with most chronic liver diseases and affects millions of people. During the last decade, major breakthroughs have been accomplished in the field of hepatic fibrosis including the discovery of key components of the extracellular matrix, the cellular origin of most matrix proteins, the molecular mechanisms involved in their synthesis and degradation, and the role of cytokines in fibrogenesis. Most of this progress came from the development of new techniques including in vitro model systems which have proven useful for investigating the molecular bases of fibrogenesis. From basic research to clinical application, two major fields are now actively explored: the search for reliable serum markers of fibrogenesis and the discovery of drugs that prevent cirrhosis. A recent approach to treat hepatic fibrosis is to use cytokines, e.g. interferons, that modulate extracellular matrix synthesis. PMID- 8340601 TI - Changes of sex hormone levels in patients with hepatitis B virus-related postnecrotic cirrhosis: relationship to the severity of portal hypertension. AB - The effect of portal hypertension on plasma sex steroid levels was studied in 49 patients with hepatitis B virus-related postnecrotic cirrhosis. In accordance with the Child-Pugh classification, 18 patients were classified as grade A, 15 grade B and 16 grade C. At the same time, 25 males who were admitted for physical check-up served as normal controls. Serum testosterone levels decreased (3.31 +/- 2.03 vs. 5.65 +/- 0.13 ng/ml) and estrone levels increased (0.16 +/- 0.08 vs. 0.09 +/- 0.02 ng/ml) significantly in patients with cirrhosis compared to the levels obtained in the controls. Moreover, these changes were associated with an increased severity of cirrhosis (P < 0.05 when severity increased from grade A to C). Hemodynamic values regarding hepatic venous pressure gradient and cardiac output demonstrated significant differences in patients from grade A to C, but the correlation between these two parameters was poor (r = 0.3242). The hepatic venous pressure gradient, the only direct measurement of portal hypertension, did not correlate with any of the measured hormone levels in patients with cirrhosis. There was, however, a highly significant negative correlation between cardiac output and testosterone levels (r = -0.8754, P < 0.01) and a positive correlation between cardiac output and estrone levels (r = 0.7522, P < 0.05) in grade C patients. On the basis of these results, we concluded that gonadal dysfunction is a common finding in patients with hepatitis B related postnecrotic cirrhosis, especially in those with decompensated liver function. The relationship between cardiac output and severity of liver disease suggests that the degree of portosystemic shunting probably increases as liver disease worsens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340602 TI - Splenic function, assessed by quantification of erythrocyte membrane pits, is normal in chronic active hepatitis and primary biliary cirrhosis. AB - Splenic hypofunction has been described in a number of diseases in which autoimmune mechanisms are believed to play a part. It has been reported in association with chronic active hepatitis although this relationship has not been systematically investigated. Twenty patients with chronic active hepatitis and 22 patients with primary biliary cirrhosis, together with an equal number of age matched controls for each group, were studied. Splenic function was assessed by counting pits on erythrocytes viewed under differential interference contrast microscopy. There was no difference between splenic function in either chronic active hepatitis, or primary biliary cirrhosis, and normal controls. In both groups of patients splenic hypofunction was significantly related to age. PMID- 8340603 TI - alpha-Interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers. AB - Forty patients with chronic viral hepatitis or active cirrhosis (33 anti-HCV positive) entered a recombinant human alpha 2A interferon randomized trial. Twenty-one subjects were treated with 6 million units (MU) three times per week for 6 months. Nineteen were not treated. Six months later in 12 patients of the treated group (60% of the evaluable 20) with normalized serum aminotransferases levels (responders), fibrogenesis serum markers (NPIIIP and laminin) were significantly lower than baseline. In the untreated patients and in non responders NPIIIP and laminin were unchanged. Semi quantitative histological evaluation (allotting scores for inflammation, necrosis and fibrosis) confirmed a significant improvement of necro-inflammation in the responders. These data suggest that alpha-IFN treatment may decrease stimuli for fibrogenesis by reducing liver inflammation and necrosis, thus preventing evolution to cirrhosis. PMID- 8340604 TI - Low prevalence of precore mutations in hepatitis B virus DNA in fulminant hepatitis type B in France. AB - The presence of mutants of the precore region of the hepatitis B virus genome was investigated in French patients with fulminant hepatitis. Only one of the 10 subjects had a detectable mutation by direct sequencing. On the other hand, 2/10 and 3/10 had evidence of coinfection by hepatitis D virus and hepatitis C virus. These results indicate that the precore stop mutation at codon 28 is not a general condition in fulminant hepatitis B and might reflect epidemiological factors. PMID- 8340605 TI - Preservation-induced liver injury. Clinical aspects, mechanisms and therapeutic approaches. PMID- 8340606 TI - Serum and salivary caffeine clearance in cirrhosis. Any role in selection for surgery and timing for transplantation? PMID- 8340607 TI - Acute cholestatic liver injury induced by enoxacin. PMID- 8340608 TI - The response of rat liver perisinusoidal lipocytes to polypeptide growth regulator changes with their transdifferentiation into myofibroblast-like cells in culture. AB - During culture on uncoated plastic wells rat liver perisinusoidal lipocytes change their differentiated phenotype (transdifferentiate) within 1-2 weeks and obtain a myofibroblast-like phenotype (myofibroblast-like cells). This transdifferentiation was documented by morphologic (loss of fat droplets, flat cell shape, cytoplasmic extensions, expression of iso-alpha smooth muscle actin) and biochemical criteria (loss of retinyl-palmitate, enhanced matrix synthesis). Whereas transforming growth factor alpha (TGF alpha) stimulated and transforming growth factor beta (TGF beta 1) inhibited the proliferation of perisinusoidal lipocytes (early culture) these cytokines did not effect the growth of the myofibroblast-like cells. Opposite effects were obtained with platelet-derived growth factor (PDGF) which stimulated the growth of myofibroblast-like cells only. Insulin-like growth factor (IGF1) was mitogenic in both perisinusoidal lipocytes and myofibroblast-like cells, respectively. Furthermore, whereas the expression of the mRNAs of decorin and biglycan was stimulated by TGF beta 1 in perisinusoidal lipocytes, the synthesis of these mRNAs was stimulated in myofibroblast-like cells predominantly by TGF alpha. Similar effects of TGF alpha and TGF beta 1 have been observed on the glycosaminoglycan-([35S]sulfate incorporation) and proteoglycan level ([3H]leucin incorporation into decorin and biglycan). Neither IGF1 and PDGF stimulated glycosaminoglycan synthesis in perisinusoidal lipocytes or in myofibroblast-like cells. The results demonstrate that the effects of the polypeptide growth regulators TGF alpha, TGF beta 1 and PDGF depend on the cell phenotype (stage of cell activation/transdifferentiation) and may be completely different in perisinusoidal lipocytes and its transformed counterpart the myofibroblast-like cells. PMID- 8340609 TI - Hepatitis B virus heterogeneity, one of many factors influencing the severity of hepatitis B. AB - The pathogenesis of hepatitis B can be subdivided into three sequentially correlated events: (a) loss of virus tolerance, (b) liver cell necrosis mediated by virus specific inflammatory response, (c) non-specific death of functionally compromised hepatocytes mediated by inflammatory cytochines released by virus specific inflammatory response. The severity of liver damage depends on the occurrence of these events as well as other factors. The HBeAg defective mutant appears to be involved in the loss of virus tolerance and therefore in the pathogenesis of acute hepatitis B. In addition it is positively selected by antiviral immunoreaction, behaves as an escape mutant, and it also contributes to the pathogenesis of chronic hepatitis B. The combination of these characteristics explains the relative prevalence of this mutant over wild-type HBV in patients with severe acute hepatitis B and in chronic HBsAg carriers during anti-HBe seroconversion and/or hepatitis B exacerbations. However, the absence of HBeAg defective mutants in some cases of severe and fulminant hepatitis B as well as its detection in asymptomatic carriers of HBsAg should not be surprising. The severity of hepatitis is influenced by many other factors: the number of virus infected cells, the competence and genetic heterogeneity of the immune system, the vigor and extent of non-specific inflammatory response and the killing of hepatocytes endangered by other diseases or infected with other hepatotropic viruses. PMID- 8340610 TI - Heterogeneity of hepatitis B virus C-gene sequences: implications for amplification and sequencing. AB - Occasionally direct sequencing of amplified hepatitis B virus DNA leads to weak signals on autoradiograms. Using amplified C-gene sequences we investigated whether this is due to sequence heterogeneity of virus populations and use of inappropriate primers for direct sequencing. High C-gene sequence heterogeneity (point mutations, stop codons and a one codon deletion) was observed in HBV genomes from serum of a chronic carrier who underwent interferon treatment. The type of C-gene mutations detected by direct sequencing depended on the type of primers used. Cloning and sequencing of amplified C-gene sequences demonstrated that this was due to mutations in the region complementary to the sequencing primer. These data demonstrate the existence of novel HBV C-gene mutants and imply that multiple or degenerate sequencing and amplification primers are essential for accurate evaluation of the extent of HBV C-gene heterogeneity. Based on comparative sequence analysis of all available completely or incompletely sequenced C-genes, guidelines for optimal primer design are proposed for similar studies. PMID- 8340611 TI - Prednisolone stimulates hepatic glutathione synthesis in mice. Protection by prednisolone against acetaminophen hepatotoxicity in vivo. AB - Mediators of inflammation modulate the extent of hepatocellular necrosis following the administration of hepatotoxins. Since corticosteroids interfere with the generation of some of these mediators they might thus protect against the hepatotoxicity of drugs such as acetaminophen. To test this hypothesis mice were pretreated with two doses of prednisolone (10 and 20 mg/kg i.p., 17 and 2 h, respectively) prior to a hepatotoxic dose of 375 mg/kg acetaminophen and the metabolism and toxicity of acetaminophen were assessed. Twenty-four hours after acetaminophen the activity of ALT in plasma (737 vs. 6775 U/l) and the extent of hepatocellular necrosis (4 vs. 45% necrotic hepatocytes) were significantly lower in prednisolone-pretreated mice. Prednisolone pretreatment resulted in decreased covalent binding of the toxic metabolite in vivo and an increased urinary excretion of glutathione-derived conjugates of acetaminophen, indicating an enhanced detoxification of the reactive metabolite by glutathione. Nevertheless, hepatic glutathione was less depleted by acetaminophen in the prednisolone group, indicating an increased capacity to resynthesize glutathione. This was confirmed in experiments with diethyl maleate which depletes hepatic glutathione without causing cell injury. Following the administration of diethyl maleate to fed and fasted mice, hepatic glutathione was depleted to the same extent after 45 min, but was significantly higher after 2.5 h in prednisolone-pretreated mice. The present results indicate that prednisolone increases the capacity to replete depleted hepatic glutathione stores in mice. PMID- 8340612 TI - Angiographically determined arteriopathy in liver graft dysfunction and survival. AB - We evaluated the contribution of flush and selective hepatic angiography in defining the extent and pattern of major vessel and microvascular arterial lesions and their significance in graft survival. The 50 consecutive patients investigated comprised three clinical groups: Group A (n = 18) were patients with severe graft dysfunction within the first seven days post-transplantation. In this group six of 18 angiograms demonstrated intrahepatic attenuation of the arterial tree suggestive of acute cellular rejection and four of these grafts were lost, compared to a 78% graft survival in the non-arteriopathic group. Group B (n = 16) comprised patients with clinically suspected hepatic arterial thrombosis or stenosis, these diagnoses were confirmed in all patients compared to only 10 positive findings with doppler ultrasonography. Graft survival was only 10% in those patients with artery thrombosis as compared to 100% in those with arterial anastomotic stenoses. Group C patients (n = 16) had histologically confirmed chronic allograft rejection and in ten of them (65%) evidence of arteriopathy was demonstrated despite histological evidence of arteriopathy being present in only 19% of patients. All patients in this group with arteriopathic changes lost their grafts with the exception of one successfully treated with FK506. In two other patients reversibility of chronic rejection was observed, neither of whom had evidence of an arteriopathy. PMID- 8340613 TI - Reversibility of cholestatic changes following experimental common bile duct obstruction: fact or fantasy? AB - In 36 male Wistar rats extrahepatic cholestasis was induced by ligation and transsection of the common bile duct. After 1, 2 and 3 weeks of cholestasis the bile flow was restored by means of a Roux-en-Y choledochojejunostomy. Plasma levels of bilirubin, alkaline phosphatase, GOT and clotting factor X were measured weekly. Liver biopsies were taken at the time of restored bile flow as well as 3 and 8 weeks thereafter. Histochemical reaction for lactate dehydrogenase activity and Sirius Red F3BA staining were used as measure for functional liver parenchyma and collagen, respectively. Acid phosphatase, alkaline phosphatase and 5'-nucleotidase activities as well as the glycogen content were demonstrated in cryostat sections of the same biopsies. After 1, 2 and 3 weeks of common bile duct obstruction, levels of bilirubin, alkaline phosphatase and GOT significantly increased, whereas levels of clotting factor X decreased. RBF resulted in normalization of all these levels to control range. The volume density of functional parenchyma was found to be reduced to 90%, 73% and 64% of the control values following 1, 2 and 3 weeks of common bile duct obstruction respectively, returning to 96%, 94% and 88% at 8 weeks, respectively, after restored bile flow. The collagen content increased significantly during cholestasis up to 5-fold after 3 weeks of common bile duct obstruction. After restored bile flow, a slight decrease of collagen was measured in some animals but in none of the three groups a return to normal values appeared. Cholestasis induced an alteration in localization and/or activity of the three enzymes analyzed as well as a depletion of glycogen stores. All changes in activity and distribution pattern of the three enzymes, as well as the glycogen depletion during common bile duct obstruction normalised after restored bile flow was performed. However, the longer common bile duct obstruction had existed, the longer period was needed for full recovery. In conclusion, even after 3 weeks of common bile duct obstruction the parenchyma/stroma relationship grossly normalized after restored bile flow with an almost complete restoration of the parenchyma and a concomitant recovery of liver function. However, collagen once formed, did not disappear but remained as more condensed septa, which apparently did not interfere with normal function. PMID- 8340614 TI - Epidemiologic findings in congenital anemia, dyserythropoiesis, and dyskeratosis in polled Hereford calves. AB - Congenital dyserythropoiesis and dyskeratosis occur within certain lines of Polled Hereford cattle. Eighty-nine of 90 alleles in 45 affected calves had a mechanism in which they could be identical by descent from an identified common ancestor. The line allele may have been a recurrence of the mutation, or the mutation may have occurred earlier in the breed's history and been distributed throughout the breed by the extensive use of several ancestors. No evidence of disease has been identified in sire and dams of affected calves, suggesting that the allele is not acting in a dominant or incompletely dominant manner. Even distribution of cases between sexes suggests that the disease is not sex linked or sex influenced. A higher degree of inbreeding in the affected calves and temporal and spatial features that separated individual cases also suggest a genetic cause. Segregation ratios were not significantly different from those of the hypothesized simple autosomal recessive inheritance. PMID- 8340615 TI - Genetic analysis of evolutionary relationships among deer (subfamily Cervinae). AB - The evolutionary relationships among 10 taxa of deer from the four genera of the subfamily Cervinae (Cervus, Elaphurus, Axis, and Dama) were examined by a comparison of their electrophoretic types for 22 proteins. We analyzed the data using both phenetic and cladistic methods and found that the genera of the Cervinae were not monophyletic. The genus Cervus was split into two distinct groups with red deer, wapiti (C. elaphus ssp.), and sika (C. nippon) in one clade and sambar (C. unicolor) and rusa (C. timorensis) in another. There was a close genetic relationship between the genus Elaphurus and the red deer, wapiti, sika group, whereas sambar and rusa were more similar to members of the genera Dama and Axis than to the other members of their own genus. These findings contrast with the taxonomy of the species that is based largely on studies of comparative morphology. Our samples (n = 5) showed fixed allelic differences between wapiti and red, wapiti and sika, and red and sika samples at 3, 6, and 7 loci, respectively. Analysis of these protein loci in a wider range of C. elaphus and C. nippon subspecies could resolve debate over the evolutionary relationships of these taxa. PMID- 8340616 TI - Microsatellite repeats in pig (Sus domestica) and chicken (Gallus domesticus) genomes. AB - Separate databases were made for all pig and chicken sequences in the Genbank database, which were then systematically searched for all possible mononucleotide, dinucleotide, trinucleotide, and tetranucleotide repeats of about 20 bp or greater in length. A total of 13% of pig genes and 10% of chicken genes contained one or more of these microsatellite-like repeats. There was a considerable difference in the frequency of dinucleotide repeats between pigs, where they comprised 30% of the repeats found, and chickens, where they comprised only 12%. The AC/GT category displayed the greatest difference: seven cases were found from 181 genes in pig (3.9%), whereas only five were found from 531 genes in chicken (0.9%). There appears to be a substantial difference in the spectrum of microsatellites between pigs and chickens. Primer sequences for amplifying these microsatellites are presented. PMID- 8340617 TI - Population characteristics of DNA fingerprints in humpback whales (Megaptera novaeangliae). AB - Humpback whales exhibit a remarkable social organization that is characterized by seasonal long-distance migration (> 10,000 km/year) between summer feeding grounds in high latitudes and winter calving and breeding grounds in tropical or near-tropical waters. All populations are currently considered endangered as a result of intensive commercial exploitation during the last 200 years. Using three hypervariable minisatellite DNA probes (33.15, 3'HVR, and M13) originally developed for studies of human genetic variation, we examined genetic variation within and among three regional subpopulations of humpback whales from the North Pacific and one from the North Atlantic oceans. Analysis of DNA extracted from skin tissues collected by biopsy darting from free-ranging whales revealed considerable variation in each subpopulation. The extent of this variation argues against a recent history of inbreeding among humpback whales as a result of nineteenth- and twentieth-century hunting. A canonical variate analysis suggested a relationship between scaled genetic distance, based on similarities of DNA fingerprints, and geographic distance (i.e., longitude of regional subpopulation). Significant categorical differences were found between the two oceanic populations using a multivariate analysis of variance (MANOVA) with a modification of the Mantel nonparametric permutation test. The relationship between DNA fingerprint similarities and geographic distance suggests that nuclear gene flow between regional subpopulations within the North Pacific is restricted by relatively low rates of migratory interchange between breeding grounds or assortative mating on common wintering grounds. PMID- 8340618 TI - Chromosomal localization of omega and trophoblast interferon genes in goat and sheep by fluorescent in situ hybridization. AB - Fluorescent in situ hybridization (FISH) of the cattle cDNA probe bTP-509 to goat (Capra hircus L.) and sheep (Ovis aries L.) R-banded metaphase chromosomes localized the omega (IFNW) and trophoblast (IFNT) interferon genes to goat chromosome 8q15 and sheep chromosome 2p15. Caprine chromosome 8 and ovine chromosome 2p are equivalent in banding pattern to cattle chromosome 8. Since FISH has previously localized IFNW and IFNT genes to cattle chromosome 8q15 and river buffalo 3q15, the localization of IFNW and IFNT genes in goat and sheep provides evidence in support of the hypothesis that chromosome-banding homology among these four species is indicative of underlying genetic homology. PMID- 8340619 TI - Coat color genetics of Peromyscus: II. Tan streak--a new recessive mutation in the deer mouse, P. maniculatus. AB - The first mutant tan streak deer mice appeared in the initial laboratory-bred generation of a stock of Peromyscus maniculatus nubiterrae collected in Macon County, North Carolina. Laboratory progeny from the original animals were bred and mated among themselves and to wild-type individuals. The tan streak phenotype is characterized by nearly complete absence of coat pigmentation, except for a pale tan patch or narrow stripe extending mid-dorsally posteriorly from the head. The band is frequently somewhat broader in the shoulder region, occasionally forming a cross-shaped pattern. There is no evidence of black eumelanin in any part of the coat. The eyes are fully pigmented, appearing black, and pigment is present in the skin of the ears and elsewhere. The trait is inherited as an autosomal recessive. The genetic locus is provisionally designated tns. Crosses between homozygous tan streak (tns/tns) animals and albino (c/c), ivory (i/i), non-agouti (a/a) and brown (b/b) deer mice produced only wild-type progeny, indicating that the tns mutation is not at any of these loci. PMID- 8340620 TI - Coat color genetics of Peromyscus: III. Golden-nugget--a recessive trait in the white-footed mouse, P. leucopus. AB - A novel pelage color variant appeared in a laboratory colony of white-footed mice (Peromyscus leucopus) from Massachusetts. The mature adult coat color of this variant exhibits a rich golden tan appearance on the dorsum with white underparts. The trait is inherited as an autosomal recessive. Phenotypic comparisons with other rodents suggest that the trait is attributable to an allele at the brown (b) locus. Under laboratory conditions homozygous or heterozygous golden-nugget Peromyscus do not differ significantly from the wild type in litter size, litter survival, nest defense, or body weight. The possibility that the allele confers some adaptive value in nature is considered. The trait is given the tentative designation bgn (golden-nugget). PMID- 8340621 TI - Alternative approaches to pterygomaxillary separation. AB - Pterygoid plate fractures, resulting from the pterygomaxillary separation in a Le Fort I osteotomy, may be associated with untoward fractures that extend to the base of the skull and orbit and which can lead to rare but significant complications. Five alternative approaches to the pterygomaxillary dysjunction were studied in 50 fresh cadavers. The results of this study show that the use of a curved Obwegeser osteotome to achieve the pterygomaxillary dysjunction should be abandoned, as it leads to an unacceptably high incidence of high-level pterygoid plate fractures at, or near, the base of the skull. The best results were obtained with a Stryker micro-oscillating saw. PMID- 8340622 TI - Bilateral coronoid process hyperplasia and short stature. A case report. AB - A 23-year-old man with bilateral coronoid process hyperplasia and short stature is presented. These findings are characteristic features of trismus pseudocampylodactyly syndrome. However, in this patient the pseudocampylodactyly component and family history were absent. PMID- 8340623 TI - Palatal opening of the nasopalatine duct. A case report. AB - An unusual case of patent nasopalatine duct appearing in the central region of the hard palate in a young adult is reported. The origin and clinical symptoms of this anomaly are discussed. PMID- 8340624 TI - Early results from reconstruction of severely atrophic (Class VI) maxillas by immediate endosseous implants in conjunction with bone grafting and Le Fort I osteotomy. AB - This report presents our experience with 12 consecutive patients treated by the method of SAILER19, comprising bone grafting to the floor of the nose and the maxillary sinus after a Le Fort I inferior repositioning of the maxilla followed by immediate implantation of endosseous implants. The corticocancellous grafts were harvested from the iliac crest. Fifty-nine implants were inserted in the bone grafts and eight in the adjacent nongrafted bone. Fourteen implants (21%) had to be removed because of nonintegration, of which 10 had been placed in two patients. The follow-up ranged from 11 to 24 months. No implants have been lost after loading. Six patients received fixed prostheses, and four overdentures. The importance of complete preoperative positional stability of the bone grafts and implants is emphasized. PMID- 8340625 TI - A comparison of morbidity following the removal of lower third molars by the lingual split and surgical bur methods. AB - Fifty-two consecutive healthy patients with bilateral, similarly impacted mandibular third molars were studied. For each patient, both third molars were removed at the same operation by the same experienced operator. On one side, the lingual split method by chisel was used; on the other, the buccal approach with surgical bur. Standard preoperative and postoperative drug regimens were used. Pain, facial swelling (visual analogue scales), and lingual and labial sensory disturbance were recorded for each side by the patients at home 6, 24, and 48 h and 7 days after surgery. Wound healing was assessed at 4 weeks. There were no statistically significant differences between methods in relation to pain, facial swelling, sensory loss, infection, or periodontal pocket depth distal to the second molar, although 2% of third molars removed by chisel had lingual sensory disturbance at 7 days, as compared with 8% where burs had been used. There were no statistically significant differences between duration of procedures; mean operating time with burs was 8.28 min (range 4-15 min) and with chisels 7.57 min (range 4-15 min). This study provided no evidence of difference in either efficiency or outcome between two standard methods of removing lower third molars. PMID- 8340626 TI - Giant cell lesions complicating fibro-osseous conditions of the jaws. AB - Three patients who presented with giant cell lesions complicating ossifying fibroma, Paget's disease, and cherubism are reported. The giant cell lesions complicating ossifying fibroma and cherubism were diagnosed as giant cell granuloma (GCG), whereas the lesion complicating Paget's disease demonstrated more aggressive clinical and histologic features. The possible therapeutic and prognostic implications of these findings are discussed. PMID- 8340627 TI - Surgical considerations in cases of large mandibular odontomas located in the mandibular angle. AB - The surgical treatment of two large, complex odontomas of the angle of the mandible is described. It is recommended that the surgeon consider excision by an intraoral, lingual approach when indicated. The advantages, indications, and possible complications of this approach are discussed. PMID- 8340628 TI - Central odontogenic fibroma. A case report. AB - A case of a central odontogenic fibroma in a 16-year-old boy is presented. The clinical appearance and surgical treatment are described; and the pathogenesis and histopathologic diagnosis are discussed. PMID- 8340629 TI - Nodular fasciitis in a temporomandibular joint. AB - A patient is presented with nodular fasciitis of the right temporomandibular joint. The clinical presentation and radiologic and light microscopic findings are described. Clinicians should be aware of this condition, particularly when there is a history of trauma. PMID- 8340630 TI - The de Lange syndrome in association with a bleeding tendency: oral surgical implications. AB - A patient with de Lange syndrome who also had a variant of von Willebrand's disease is reported. The problems with dental surgery, particularly with respect to difficulty of extraction and bleeding tendency, are discussed. PMID- 8340631 TI - Three-dimensional ultrasonography in maxillofacial surgery. A new diagnostic tool. AB - Three-dimensional (3-D) ultrasonography is introduced as a new diagnostic method for soft-tissue lesions. This method is based on the production of absolutely parallel brightness (B)-scan tomographies with constant intervals. After adequate preparation, the sonographic primaries are processed into 3-D graphs by a specialized program called EUCLID-IS. This method promises to be useful in the evaluation of tumor patients as well as in the follow-up examination of these patients. The main advantages of the presented method are the capacity to measure accurately the volume of regions of interest and the excellent visualization of the structures examined. PMID- 8340632 TI - The behaviour of mandibular condylar cartilage in cell culture. AB - This investigation aimed to identify the behaviour of primate mandibular condylar cartilage cells in an in vitro model. Cells were harvested from the mandibular condyles of 1-year-old marmosets and maintained in primary culture for up to 30 d. Cell proliferation, structure, and phenotype were assessed at regular intervals by phase-contrast microscopy, cytologic staining, and immunocytochemistry. Cell growth increased progressively, and cultures reached confluence after 22 d. Cells were initially small and round but later became enlarged and heterogeneous in shape. Polygonal and hypertrophic chondroblast-like cells dominated the mature cultures. Glycosaminoglycan synthesis increased as cultures aged. Type I collagen was produced by early cultures, whereas type II collagen predominated in mature confluent monolayers. It is suggested that this mixed population of cells underwent phenotypic changes in primary cell culture that closely resemble the normal in vivo maturation process. PMID- 8340633 TI - Should titanium miniplates be removed after bone healing is complete? AB - A prospective study of 32 patients was performed to analyze black pigmentation in the soft tissue covering titanium miniplates. This soft tissue was compared with the soft tissue covering Champy stainless steel plates. All plates were removed 8 months after application. Macroscopically visible pigmentation was found in 25.6% of the soft tissue covering titanium miniplates and in none of the soft tissue covering Champy stainless steel plates. Microscopically visible pigmentation was found in 71.8% of the soft tissue covering titanium miniplates and in 65.3% of the soft tissue covering Champy stainless steel plates. Energy-dispersive x-ray analysis of the soft tissue covering titanium miniplates revealed only the presence of titanium dioxide. In the soft tissue near Champy stainless steel plates, chromium, nickel, iron, and molybdenum were found. Electron microscopy showed titanium dioxide to be mainly deposited between the collagen fibers, whereas stainless steel particles were mainly found in giant cells. PMID- 8340634 TI - Let's be careful out there. PMID- 8340635 TI - The MMSE to assess the cognitive state of elders. Mini-Mental State Examination. AB - In both nursing practice and research settings, valid and accurate information on the cognitive function of elderly persons is necessary. However, methods and criteria for evaluating an elder's mental status are inconsistent. A formal screening tool such as the Mini Mental State Examination (MMSE) would enable nurse clinicians and researchers to use a common method for identifying cognitive impairment. In addition, the MMSE score can readily describe levels of impairment across settings. Although certain limitations exist when using this instrument, the MMSE has been successfully employed by some nurses in selected clinical and research settings as a brief but accurate screen of cognition in older persons. PMID- 8340636 TI - Enhancing recovery via neuro-rehab rounds. AB - The neurologically injured patient experiences physiological and psychological disruptions regardless of the type of severity of injury. Through increased knowledge, nurses planning care can minimize loss of functional ability, anticipate complications and enhance recovery. Neuro-rehab rounds were developed to increase the involvement of support therapies for the patient in the neurotrauma intensive care unit (ICU) of a particular hospital. Increasing the critical care nurses' awareness of rehabilitation principles was the secondary goal. This protocol decreased length of stay, increased mobilization of patients in the ICU and provided for continuity of care for the neurologically injured patient. Rounds also redirected and expanded the focus for critical care nurses from episodic to one more outcome related. PMID- 8340637 TI - Bacterial ventriculitis and duration of ventriculostomy catheter insertion. AB - Invasive monitoring of intracranial pressure (ICP) plays an important role in managing many neurosurgical patients. While there are several techniques available to monitor ICP, the ventricular catheter is most commonly used and the most accurate. ICP monitoring poses potential risks to the patient. The most common and one of the most devastating complications is infection. This research study examined the rate of bacterial ventriculitis in relation to duration of ventricular catheter insertion as well as other factors which may contribute to ventriculitis. Data were collected prospectively on 78 patients with a ventriculostomy who were 14 years of age or older and admitted to the neuroscience intensive care unit. Patients were followed from the time of ventricular catheter placement to two weeks after the catheter was removed or until the patient was discharged from the hospital. A significantly higher ventriculitis rate was found in patients with a mean catheter duration of 11 days or longer (p = .004). In the group that developed ventriculitis there was a significant rise (means = 6.03592, p = .014) in the cerebrospinal fluid (CSF) lactate prior to the onset of ventriculitis. Neuroscience nurses should be aware of the factors which may increase the rate of ventriculitis, such as duration of catheter placement and factors which may indicate impending infection such as a rise in the CSF lactate. Future studies should compare various methods of ventriculostomy site care for efficacy of infection prevention, cost and caregiver time. PMID- 8340638 TI - Investing in the comeback: parent's experience following traumatic brain injury. AB - The increasing incidence of survival following traumatic brain injury necessitates a closer examination of long-term care and caregiver issues. A sample of parents and brain-injured offspring from 20 families was explored to identify a qualitatively-generated theory describing the parent's experience following a brain-injured child's return to the home setting. The grounded theory methodology was used during data collection and analysis. All the brain-injured offspring had survived moderate to severe traumatic brain injury, were living with at least one parent, and were aged 17-34 years. Investing in the Comeback is the generated three-phase theory. These three phases--centering on, fostering independence and seeking stability describe the work of parents living with brain injured offspring. PMID- 8340639 TI - Multiple sclerosis: a literature review. AB - The pathology of multiple sclerosis (MS) was first described over 150 years ago. An estimated 250,000 to 350,000 people are affected with MS in this country. Young adults between the ages of 20 and 50 years are most commonly affected, with the majority of patients experiencing a relapsing course and progressive functional disability. To date, researchers have been unable to discover a precipitating cause. However, many now believe MS develops due to exposure to some unknown virus in a genetically predisposed individual. The incidence of disease is limited in temperate climates and higher in northern latitudes. Neuroscience nurses frequently care for individuals with MS and must, therefore, maintain a familiarity with the current literature and research. PMID- 8340640 TI - tPA in acute stroke--risk or reprieve? AB - Stroke outcome is measured by survival and disability. Since more patients are surviving stroke, researchers are pursuing ways to reduce the severity of neurological deficits. Anticoagulant treatment with heparin prevents, rather than treats, thrombotic or embolic occlusions; therefore, the search for safer thrombolytic preparations continues. Tissue plasminogen activator is currently under investigation as an effective, safe treatment for acute stroke patients. However, the administration of tPA carriers a risk of hemorrhage. Although this article discussed tPA administered with an arteriogram based protocol, tPA investigation occurs using other protocols. Once acute stroke patients receive tPA, then measures to prevent complications and manage the stroke symptoms determine the risks and benefits patients receive. Nursing management of these patients can contribute to these benefits. PMID- 8340641 TI - Issues related to the protection of human research participants. AB - Making ethical decisions related to the protection of human research participants is often complex and fraught with uncertainty and conflict. Awareness of the basic principles outlined in the Belmont Report as well as in federal regulations and guidelines can provide a useful framework for such decisions, although the ultimate responsibility for ensuring ethical research practices rests with the individual investigator. Ongoing dialogue and discussion about these ethical issues will provide a basis for strengthening nursing research and practice while ensuring the maximum protection for research participants who make possible the advancement of nursing science. PMID- 8340642 TI - Evaluating research findings for clinical applicability. AB - Despite the emphasis upon research and research-related activities in nursing practice, the evaluation and subsequent utilization of research findings by those in direct contact with patients is minimal. Reasons for limited use include educational level of nurses, lack of availability of research findings to nurses in the practice setting and inadequate communication between nurses in the educational and service settings. Prior to using the findings from any research study, the study's findings must be evaluated. This process includes identification of the researchable problem or question, exploration of available completed studies, determination of applicability, implementation, assessment and evaluation. The final step of the process is the dissemination of the findings of the evaluation through inservice or continuing education programs or local, regional or national conferences. Publications also provide an avenue by which findings can be disseminated. PMID- 8340643 TI - [A study on cervical cerclage for a dilated cervix or bulging membranes without rupture of membranes]. AB - During the period January 1, 1989 through December 31, 1991, one hundred thirty six pregnant women with an effaced and widely dilated cervix or with bulging membranes were treated by emergent cervical cerclage. Suturing was carried out in 16 women before 20 weeks gestation, in 86 women between 20 and 28 weeks and in 34 women after 28 weeks. 16 patients in group A were those whose pregnancy was terminated with 3 days after operation and their tocolysis index was significantly higher than that of 69 patients in group D, whose pregnancy was prolonged move than two weeks. Clinical chorioamnionitis (WBC > 15,000/mm3 and CRP > 2mg/dl) was occurring in 43.7% of patients in group A, compared with 8.7% in group D at the time of operation. Vaginal delivery was accomplished in 38 patients at between 24 and 36 weeks gestation in our hospital, while 41 cesarean sections were performed. On the basis of these results, we conclude that the emergency cerclage operation may improve the outcome of pregnancy but we have to pay special attention to premature rupture of membranes and chorioamnionitis. PMID- 8340644 TI - [Measurement and its fluctuation of urinary glucaric acid in newborns]. AB - It is known that urinary excretion of glucaric acid(GA) is an indirect index of hepatic P-450 microenzyme induction. We measured and analyzed urinary excretion of GA in 56 newborns and 26 mothers by a new method for the inhibition of beta glucuronidase activity and obtained the following results. 1. The concentration of urinary GA was correlated with that of urinary creatinine and total bilirubin in newborns. 2. There were no significant correlations between gestational age, sex, body weight at birth, placental weight and the urinary GA concentration. 3. The urinary excretion of GA in newborns was decreased the in first few days after birth, but a transitional increase was observed on the fifth day after birth. 4. The concentration of urinary GA was correlated with that of direct bilirubin in serum on the fifth day after birth. 5. There was a negative correlation between the urinary GA concentration on the first day after birth and that of direct bilirubin in serum on the fifth day after birth. These results suggested that hepatic P-450 microsomal enzyme was induced by bilirubin in newborns and it was possible to estimate the clinical course of jaundice by measuring the urinary excretion of GA. PMID- 8340645 TI - [Doppler flow velocity waveforms in uteroplacental and fetal circulation in normal pregnancy and pregnancy-induced hypertension]. AB - The present study was conducted to elucidate circulation dynamics in uteroplacental and fetal circulation in 130 normal pregnancies and in 40 patients with pregnancy-induced hypertension (PIH). A sector and pulsed Doppler system was employed to measure the uterine artery pulsatility index (UtA-PI), umbilical artery pulsatility index (UAPI), fetal middle cerebral artery pulsatility index (MCPI) and fetal descending aorta peak velocity (AoPV). Furthermore, peak velocity during early diastolic (E) and atrial contraction (A) periods through the mitral (M) and tricuspid (T) valves was measured to determine their ratios (M E/A and T-E/A). Twelve of the 40 PIH women had UtA-PIs of 95% or higher in normal pregnant women. Ten of the 12 fetuses in women with high UtA-PIs had high UAPIs, 5 of whom demonstrated an MCPI decrease. Two of them represented an increase in M E/A and a decrease in T-E/A and AoPV, and the prognosis was poor. Only 2 of the PIH women with normal UtA-PIs had high UAPIs. The fact that both M-E/A and T-E/A were inversely correlated with MCPI and UAPI, respectively, suggests that these parameters could be used as indexes demonstrating cardiac afterload in fetuses. UtA-PI measurement in combination with fetal circulation indexes could predict fetal and neonatal well-being. PMID- 8340646 TI - [Biopsy of mouse embryo fertilized in vitro as a preclinical model for preimplantation genetic diagnosis]. AB - In preimplantation genetic diagnosis, it is vital that the biopsy method does not affect embryonic development and yet provides a suitable specimen for genetic diagnosis. This study investigated whether the expulsion method, a modification of the displacement and extrusion methods, could satisfy the above mentioned conditions. Mouse embryos fertilized in vitro were biopsied at the 4, 8 and 16 cell stages, and were subsequently observed for in vitro and in vivo development. The rates of blastocyst formation, implantation, and fetal growth in the 8- and 16-cell biopsy groups were not significantly different from those in the control groups, but all 3 parameters were significantly reduced in the 4-cell group. Fetal and placental development was similar to the control group when embryos were biopsied at all three stages. Single blastomeres obtained by expulsion biopsy were subjected to DNA amplification by dual PCR, and Sry and myogenin sequences were amplified. In conclusion, expulsion biopsy did not affect the development of 8- and 16-cell embryos, and the specimens obtained were adequate for DNA amplification. PMID- 8340647 TI - [Treatment of ovarian cancer at FIGO stage III and IV--prognostic factors for patients receiving neoadjuvant chemotherapy]. AB - Among 165 patients with stage III and IV ovarian cancer, 74 received neoadjuvant (NA) chemotherapy. The response to NA chemotherapy was 85% (17/20) for CP, 79% (26/33) for CAP, and 33% (7/21) for FAMT. Following NA chemotherapy, 43 patients received debulking surgery, of whom 34 received optimal debulking (OD: residuum < 2cm). The remaining 31 patients did not receive debulking, of whom 18 responded to NA chemotherapy. The rate of OD was significantly higher in patients with CAP/CP than in those with FAMT. There was a tendency for the OD rate to be higher in patients with the serous or endometrioid type than in those with the clear cell or mucinous type. The procedures employed in 34 patients receiving OD following NA chemotherapy included basic surgery for 24 patients and more extensive surgery for 10 patients. Significant prognostic factors for patients receiving NA chemotherapy were, 1) response to NA chemotherapy, 2) radicality of debulking following NA chemotherapy, 3) regimen of NA chemotherapy (CAP/CP), and 4) histologic type (serous, endometrioid). PMID- 8340648 TI - [Effects of human macrophage-colony stimulating factor (hM-CSF) on the secretion of human placental lactogen in human chorionic villous cells]. PMID- 8340649 TI - [Induction of M-CSF and G-CSF receptor mRNA in peripheral blood mononuclear cells of gynecological cancer by sizofiran]. PMID- 8340650 TI - [A surgical correction of urinary stress incontinence by vaginal route--midline plication of urethral supports]. PMID- 8340651 TI - [A case of embryonal rhabdomyosarcoma (sarcoma botryoides) of in adult woman vagina]. PMID- 8340652 TI - [A case of transient fetal hydrops which would be caused by parvovirus B19 infection]. PMID- 8340653 TI - [Laparoscopy-assisted vaginal hysterectomy]. PMID- 8340654 TI - [Bone metabolism in patients with physiological menopause and oophorectomy--cross sectional study]. PMID- 8340655 TI - [Trend of clinical pathology tests and the effective usage for diagnosis]. PMID- 8340656 TI - [Reading of normal value and abnormal value in clinical tests]. PMID- 8340657 TI - [Factors influencing the results of clinical tests and need for careful handling of specimens]. PMID- 8340658 TI - [International system of units]. PMID- 8340659 TI - [New clinical tests in diagnosis of respiratory system diseases]. PMID- 8340660 TI - [New clinical tests in diagnosis of cardiovascular system diseases]. PMID- 8340661 TI - [New clinical tests in diagnosis of kidney and urologic diseases]. PMID- 8340662 TI - [New clinical tests in diagnosis of hematologic diseases]. PMID- 8340663 TI - [New clinical tests in diagnosis of endocrine and metabolic diseases]. PMID- 8340664 TI - [New clinical tests in diagnosis of infectious diseases]. PMID- 8340665 TI - [Present status of clinical pathology tests and the skillful usage for diagnosis (discussion)]. PMID- 8340666 TI - [A case of systematic lupus erythematosus with autoimmune hypophysitis]. PMID- 8340667 TI - [A case of empty sella syndrome and pan-hypopituitarism associated with acute suppurative paranasal sinusitis]. PMID- 8340668 TI - [A case of acute intermittent porphyria treated with cimetidine]. PMID- 8340669 TI - [A case of wallenberg's syndrome with systemic lupus erythematosus and antiphospholipid syndrome]. PMID- 8340670 TI - [Double-chambered right ventricle without other heart anomaly in the aged]. PMID- 8340671 TI - [Therapy of hypertension with kidney diseases]. PMID- 8340672 TI - [Gene diagnosis and gene therapy]. PMID- 8340673 TI - Introduction: genetic deficiencies of complement proteins--consequences and molecular basis. PMID- 8340674 TI - C1-inhibitor and its genetic alterations in hereditary angioneurotic edema. PMID- 8340675 TI - Genetic deficiencies of the complement system and association with disease--early components. AB - Genetic deficiency of one of the early components of the classical pathway of complement (C1q, C1r, C1s, C4 and C2) is often associated with clinical symptoms and immunochemical abnormalities common in idiopathic autoimmune diseases, such as lupus erythematosus, but also with an increased incidence of various, local and generalized infections. These observations are consistent with the current view of the complement system's role in handling immune complexes and combating microbial invasion. However, the absence of absolute correlations in these experiments of nature suggests that genetic defects of the classical pathway act only epistatically to other host factors and the primary etiologies of the associated diseases. In contrast, the strong association of properdin and factor D deficiency with serious infections caused by encapsulated Gram-negative bacteria suggests a more immediate involvement of the alternative pathway in a specific segment of immunity and its pathology. This concept is also supported by the primordial role of the alternative pathway in the evolution of the complement system and the apparent lethality of factor B deficiency. The gene structures of most of these early components have now been elucidated providing the basis for detailed analyses of the defective alleles, the determination of carrier status, and prenatal diagnosis. PMID- 8340676 TI - Hereditary deficiency of C3 in animals and humans. AB - Inherited deficiency of complement C3 has been described in guinea pigs, dogs and 20 humans. Homozygous deficiency of C3 is associated with recurrent pyogenic infections by encapsulated bacteria, especially H. influenzae, S. pneumoniae and N. meningitidis. In dogs and humans there is also an association with development of glomerulonephritis of the mesangiocapillary type. Some patients also develop transient erythematous rashes in association with pyogenic infections, with histology showing predominantly neutrophil infiltration and small vessel vasculitis. Studies of antibody responses, mainly in experimental animals have shown impaired primary and secondary responses to both thymus-dependent and independent antigens at low immunizing doses, with a reduced switch from IgM to IgG production. The molecular basis of C3 deficiency has been established in two humans with C3 deficiency. In one it was due to a splice junction mutation and in another, to a partial gene deletion. These mutations are not compatible with the production of functional C3 in any tissue. Such patients with absolute C3 deficiency are a valid model for understanding the physiological role of C3 in vivo. PMID- 8340677 TI - Inherited deficiencies of the terminal complement components. PMID- 8340678 TI - Genetics and deficiencies of the soluble regulatory proteins of the complement system. PMID- 8340679 TI - ECG of the month. Rise and fall. Narrow-QRS tachycardia with electrical alternans. PMID- 8340680 TI - Vestibular rehabilitation. AB - Vestibular dysfunction has many etiologies. Symptoms including vertigo and imbalance may severely hamper life-style, causing the afflicted individual to seek medical attention. For many patients with vestibular complaints a cure is not available. However, the physician is often called upon to relieve incapacitating symptoms. The purpose of this article is to discuss vestibular rehabilitation as a therapeutic modality for patients with chronic vestibular dysfunction. PMID- 8340681 TI - Cardiac transplantation, 1993. PMID- 8340682 TI - Cardiac transplantation: role of endomyocardial biopsy and immunosuppressive agents. AB - The field of cardiac transplantation has made tremendous strides since the first transplant procedure in 1967. This paper reviews the role of endomyocardial biopsy to diagnose and follow rejection as well as the standard immunosuppressive regimens employed. With continued refinements in immunosuppressive therapy, further improvements in mortality and morbidity rates should be realized. PMID- 8340683 TI - Medical choices in the 90s: transplantation and donation. AB - Heart transplantation is a growing field that offers the promise of meaningful life extension to individuals in end-stage organ failure. This technology is not only costly but dependent on limited access to cadaveric donor organs. Although advances in transplantation biology may someday allow for reduced cost and easy access to organs from nonhuman sources, today the "most readily available" source remains those organs which are donated by human donors. But despite the fact of being the "most readily available" they are far from being readily accessible. Due to these advances in transplantation, physicians are able to offer the "choice" of transplantation to their patients in whom end-stage organ failure exists. As more patients are referred for transplantation, the need for donor organs grows. And because of this need, physicians must begin to consider how to offer another choice, the "choice" of organ donation. In order to offer this option, knowledge of patient selection, evaluation, and suitable time of referral is important if the practitioner is to counsel potential donor families. This article provides a background and brief description of the Louisiana donor process. PMID- 8340684 TI - Cardiac transplantation: an overview of recipient selection. AB - Cardiac transplantation is an accepted treatment for end-stage heart disease. Potential recipients are carefully screened in order to best place the short supply of donor organs with the best recipient. The success of heart transplantation in the United States today is directly related to careful donor and recipient selection criteria and improvements in immunosuppression. PMID- 8340685 TI - Long-term follow-up and complications after cardiac transplantation. AB - Cardiac transplantation has become an established therapy for cardiomyopathy and other irreversible cardiac diseases. Improvements in immunosuppression and management of infections has improved long-term survival following transplantation. The role of the primary care physician in the care of recipients will be expanding. Transplant recipients receive close outpatient follow-up after discharge, primarily to monitor immunosuppression through laboratory evaluation and drug levels, monitor for rejection through endomyocardial biopsy, and to assess for any signs of opportunistic infection. The foundation for long-term immunosuppression is administration of cyclosporin, azathioprine and corticosteroids. Antibiotic prophylaxis is used to decrease the chance of infection with cytomegalovirus, Pneumocystis, Candida, Toxoplasma, and other opportunistic organisms. The major long-term complications include rejection, infection, hypertension, renal dysfunction, lipid abnormalities, and accelerated coronary atherosclerosis. This review provides an overview of the short- and long term follow-up of the cardiac transplant recipient, including routine care as well as detection and management of the common complications. PMID- 8340686 TI - Cardiac assist devices: bridging and beyond. AB - Due to the high incidence of death while awaiting cardiac transplantation today, most major transplant centers have adopted the use of left ventricular assist devices in order to stave off the complications of end-stage heart failure and allow patients to maintain a good physiologic state going into heart transplantation. These devices are safe and may one day prove to be a substitute for the short supply of donor organs. PMID- 8340687 TI - Heart transplantation: operative techniques and postoperative management. AB - Heart transplantation has become an established therapeutic option for some patients with end stage heart failure. The technique of heart transplantation involves excision of the diseased heart leaving behind cuffs of the right and left atria, pulmonary artery and aorta, which are subsequently attached to their counterparts in the procured donor heart. In most cases donor and recipient operations are carried out in two different hospitals which can be hundreds of miles apart. Careful coordination and timing of the donor and recipient operations is fundamental to keep the ischemic time (ie, the time taken to remove the donor heart, transport to the transplant center and implant in the recipient) to a minimum. Ischemic time longer than 4 hours carries a significantly higher operative mortality. Preservation of the donor heart during the period of ischemia is achieved using a potassium based cardioplegic solution which arrests the heart in diastole, and is supplemented with topical cooling to keep the myocardial temperature at 4 degrees C. Due to cardiac denervation and impaired ability to respond to high filling pressures, maintaining a fast heart rate is essential to maximize cardiac output during the early postoperative period. High pulmonary vascular resistance can occur postoperatively and can result in failure of the donor heart. This may require the use of vasodilators and mechanical right heart assistance. In addition to the use of immunosuppressive agents to prevent rejection of the donor heart, careful attention should be given to renal function and to prophylaxis against infection. The overall 30-day survival (ie, operative survival) currently exceeds 95%. PMID- 8340688 TI - A modest proposal: universal access to appropriate medical care as a means of cost reduction. PMID- 8340689 TI - ECG of the month. Benevolent rhythm. Escape impulses; escape rhythm. PMID- 8340690 TI - Head and neck manifestations of sarcoidosis. AB - Sarcoidosis is a multisystem granulomatous disease of unknown etiology affecting young adults and presenting most commonly with bilateral hilar lymphadenopathy, pulmonary infiltrates, and skin or eye lesions. The manifestations of this disease are protean and its clinical course is variable. Often the mode of onset correlates with the natural course and prognosis of the disease. Acute onset usually leads to remission within 12 to 18 months. Insidious, chronic disease often results in fibrotic sequelae. The treatment of choice for sarcoidosis is systemic corticosteroids. PMID- 8340691 TI - What is medical ethics? AB - This article is the first of a series on medical ethics which will appear at irregular intervals in the JOURNAL of the Louisiana State Medical Society. The ethical issues which will cover many of the problems encountered in clinical practice that cause a dilemma for physicians and patients. In these cases a choice usually exists and one describes the situation with words such as "should" or "ought." The author will write about current issues in medical ethics. His goal will be to describe a problem and to present the arguments for and against various solutions. He does not intend to tell you how you should react to ethical issues; that is each person's judgment. On the other hand, he will try to give you the arguments and hopes to help you to see the issue from several perspectives. PMID- 8340692 TI - How to interpret fish consumption advisories. AB - The goal of this paper is to explain the guidelines used in Louisiana to issue advisories against consumption of chemically contaminated seafood or fish and explain some of the uncertainties encountered. In the absence of federal regulations the State had to develop its own approach. The concentrations resulting from Louisiana policies are generally low in comparison with the FDA tolerances and, thereby, well within reasonable limits justified by the need to protect populations with high fish consumption. PMID- 8340693 TI - Outpatient anesthesia in the pediatric patient: a review. AB - Outpatient or ambulatory surgery has become one of the fastest growing subspecialties. The practice of outpatient pediatric surgery has numerous advantages. One of the main advantages is the shortened length of time the child is hospitalized. Careful selection of pediatric patients for outpatient surgical procedures is the best way to avoid problems and complications. The most anxiety producing aspect of the operation itself, that of parent separation, is also lessened by outpatient pediatric surgery. Preoperative evaluation and assessment is just as crucial in outpatient surgery as in all other surgical procedures. It is even more important in outpatient pediatric surgery to establish rapport with the parent and child and get a sense of the psychological needs of the patient. Pediatric outpatient surgery is still a relatively new subspecialty and from an anesthetic standpoint, the preoperative assessment is the anesthesiologist's main tool in getting to know his or her patient. PMID- 8340694 TI - Nonspecificity of meningeal enhancement in craniospinal magnetic resonance imaging. AB - Magnetic resonance imaging contrast agents are exquisitely sensitive in detecting meningeal abnormalities, which almost invariably manifest as abnormal enhancement. This property of the contrast agents is not accompanied by an equal degree of specificity, but as shown by the two case reports, contrast agents are still helpful to detect and define the extent of the meningeal abnormality, and to document its resolution, or the lack thereof. PMID- 8340695 TI - New medical/legal interprofessional code for Louisiana undergoing development.[The Medical-Legal Interprofessional Committee. The Louisiana State Medical Society and The Louisiana Bar Association]. AB - The Medical/Legal Interprofessional Committee is a cooperative committee involving representatives of the Louisiana State Medical Society and the Louisiana Bar Association. The committee is currently re-examining its Interprofessional Code and its Advisory Opinion with the intent of combining the documents into a new, concise Code designed to promote cooperation and limit conflicts between the two professions. The precepts of this Code will also guide the Committee in deciding issues and disputes between physicians and attorneys. Reprinted in this issue is the original Interprofessional Code for Physicians and Attorneys of the State of Louisiana and the Advisory Opinion of the Medical/Legal Interprofessional Committee. The Committee encourages all physicians to review these documents and to contribute their thoughts and suggestions on what should be included in the new Code and how the relationships between the two professions can be improved. Please send comments to: Louisiana State Medical Society, Medical/Legal Interprofessional Committee, 3501 N Causeway Blvd, Suite 800, Metairie, LA 70002. PMID- 8340696 TI - Endothelin: a new role for an old friend? PMID- 8340697 TI - Cocaine and reproductive cardiology. PMID- 8340698 TI - The right to participate in research studies. AB - Institutional review boards for the use of human subjects in scientific studies were initially established to focus on protection of human subjects from the risks of research. It has become evident in recent years, however, that it is also important to protect the rights of individuals to have access to the benefits of research participation. These include, but are not limited to, certain experimental drugs or treatments, closer monitoring, free care or direct remuneration, and societal benefits of results of studies on specific populations. Researchers, so long sensitized by their respective institutional review boards to the need for protection of the subjects, now must also focus on the added burden of efforts to include individuals and the increased efforts it may take to protect the safety and rights of certain populations, including patients with AIDS, women, minorities, children, and the elderly. Additional care must be taken to design appropriate studies, recruit an appropriate spectrum of the population, craft a complete yet understandable and nondeterent informed consent form, and make efforts to assure that participants are informed. PMID- 8340699 TI - Gene expression for endothelins and their receptors in glomeruli of diabetic rats. AB - The present study was designed to assess levels of messenger RNA encoding for endothelin-1, endothelin-3, and endothelin receptors A and B in glomeruli of rats with streptozotocin-induced diabetes at 4, 12, and 24 weeks of age. In addition, streptozotocin-induced rats with diabetes were either treated with 8 to 14 units neutral protamine Hagedorn insulin daily to maintain moderate hyperglycemia (approximately 200 mg/dl) or left untreated to produce severe hyperglycemia (more than 400 mg/dl) during the 4-week study period. The messenger RNA levels for endothelin-1 in glomeruli of diabetic rats increased with the progression of diabetic nephropathy (4 weeks, 2.5 times control level, p < 0.01; 12 weeks, 3.8 times, p < 0.01; and 24 weeks, 5.3 times, p < 0.001. In contrast, messenger RNA levels for endothelin receptors A and B were not altered in glomeruli from diabetic and control rats throughout the experimental period. Messenger RNA for endothelin-3 in glomeruli from diabetic and control rats was not detected until 24 weeks of age. Insulin treatment partially ameliorated the increase in messenger RNA for endothelin-1 in the glomeruli of diabetic rats (0.3 times compared with diabetic rats without insulin treatment, p < 0.01), whereas insulin treatment did not affect messenger RNA for endothelin receptors A and B in diabetic glomeruli. These findings indicate that increased endothelin-1 messenger RNA in glomeruli may be a manifestation of diabetic nephropathy, and hyperglycemia or insulin-deficiency may play a role in abnormal endothelin-1 gene regulation. PMID- 8340700 TI - Gender-related differences in cocaine toxicity in the rat. AB - To test our hypotheses that gender-related differences in cocaine toxicity exist in the rat, cocaine (2 mg/kg/min) was infused intravenously in chronically catheterized male and ovariectomized or intact female rats until the onset of circulatory collapse. Sequential manifestations of cocaine toxicity from mild central nervous stimulation to fatal cardiovascular collapse were observed. Arterial blood was withdrawn at the onset of the toxic signs or symptoms for determination of cocaine concentrations. Dosages and plasma concentrations of cocaine required to produce cardiovascular toxic manifestations were significantly lower in male and ovariectomized rats than in intact females. Plasma cholinesterase activity was lowest in the male animals and highest in intact females. These data suggest that systemic toxicity of cocaine is enhanced in male rats, because lower doses and plasma concentrations are required to induce toxic signs and symptoms. PMID- 8340701 TI - Tumor necrosis factor-induced contraction of cultured rat mesangial cells: interaction with angiotensin II. AB - The role of tumor necrosis factor alpha in the regulation of renal function, particularly glomerular filtration rate, has not been completely defined. This study was designed to assess the intrinsic role of this cytokine on glomerular filtration rate by analyzing its short-term effect on the degree of contraction in cultured rat mesangial cells, not only directly but also in the presence of angiotensin II. Contraction was evaluated both morphologically--by measuring planar cell surface area of cultured rat mesangial cells and glomerular cross sectional area of isolated rat glomeruli--and biochemically--by analyzing myosin light-chain phosphorylation in cells. Tumor necrosis factor alpha significantly decreased planar cell surface area in a dose-dependent and time-dependent manner, an effect completely abolished by preincubation of the cells with platelet activating factor receptor antagonists BN 52021 and alprazolam. This effect was also observed in the presence of angiotensin II, whether tumor necrosis factor alpha was added before or after angiotensin II, increasing the reduction in planar cell surface area induced by angiotensin II in both cases. Changes in planar cell surface area were evident not only when the absolute values of this parameter were considered but also when the percentage of contracted cells (cells with a planar cell surface area reduction > 10%) was analyzed. Tumor necrosis factor alpha also induced a significant reduction of glomerular cross-sectional area in isolated rat glomeruli. The results of the morphologic studies were supported by myosin light-chain phosphorylation experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340702 TI - Investigations on the role of hemopexin and albumin in plasma clearance and tissue distribution of Sn-protoporphyrin. AB - The mechanism of the clearance of circulating tin-protoporphyrin (Sn-PP), a competitive inhibitor of heme oxygenase in the degradation of heme to bilirubin, is unknown. Two serum proteins, albumin and hemopexin, which are instrumental in the delivery of iron-protoporphyrin (heme) to the liver, also bind metalloporphyrins with high affinity and may aid in targeting their tissue distribution. After intravenous injection of 1 mumol Sn-PP/kg, the serum concentration of hemopexin decreased in human subjects, rats, and rabbits within 24 hours to a similar extent (30% to 50%). This finding suggested that hemopexin may have a role in the tissue distribution of Sn-PP. However, when rats were injected with Sn-PP in saline solution or complexed with albumin, more Sn-PP was taken up by the liver and testes than when Sn-PP was complexed with hemopexin. These results indicate that hemopexin does not preferentially target Sn-PP to the liver and may not be the preferred vehicle for clearance of circulating Sn-PP. PMID- 8340703 TI - Glucocorticoid metabolism in the cardiac interstitium: 11 beta-hydroxysteroid dehydrogenase activity in cardiac fibroblasts. AB - The interstitial fibrosis seen in the heart and systemic organs in states of primary or secondary mineralocorticoid excess suggests that fibroblasts are responsive to mineralocorticoid. In vitro studies demonstrating increased fibroblast collagen synthesis in response to MC are consonant with this view. The nicotinamide-adenine dinucleotide phosphate(+)-dependent enzyme 11 beta hydroxysteroid dehydrogenase converts the glucocorticoids corticosterone and cortisol to the inactive metabolites 11-dehydrocorticosterone and cortisone, respectively, conferring mineralocorticoid specificity to the cells within which it is active. We investigated the presence of 11 beta-hydroxysteroid dehydrogenase in sonicates of cultured vascular endothelial cells and cardiac fibroblasts by incubating sonicates for 1 hour in the presence of 5 x 10(-9) mol/L tritiated corticosterone or tritiated cortisol (1 microCi) and using reverse-phase high-performance liquid chromatography coupled to an on-line radioisotope detector for steroid separation and quantitation. Extracts of bovine endothelial cells showed no enzymatic activity with either substrate, whereas extracts of rat cardiac fibroblasts readily converted corticosterone to 11 dehydrocorticosterone, even in the absence of exogenous nicotinamide-adenine dinucleotide phosphate+ (10% conversion). When 5 x 10(-4) mol/L nicotinamide adenine dinucleotide phosphate+ was added to sonicated fibroblasts, conversion increased to 50%, corresponding to 12 pmol 11-dehydrocorticosterone formed/mg protein. Conversion of cortisol to cortisone was not observed in fibroblast or endothelial cell extracts. Significant levels of corticosterone to 11 dehydrocorticosterone conversion (0.14 pmol/10(6) cells/hour) were detected in intact fibroblasts, but no 11-dehydrogenation of corticosterone was observed in intact endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340704 TI - The effects of inhibition of plasma cholinesterase activity on systemic toxicity and blood catecholamine levels from cocaine infusion in pigs. AB - We investigated systemic effects and possible mechanisms for lethality of intravenously infused cocaine in spontaneously breathing and mechanically ventilated unconscious Landrace male pigs weighing about 26 kg (25.75 +/- 0.25 kg) that were pretreated with either saline solution (groups 1 and 3) or iso-ompa (tetraisopropyl pyrophosphoramide), a specific plasma cholinesterase inhibitor (groups 2 and 4). Pigs were made unconscious with sodium thiopental and ventilated with 70% nitrous oxide and 30% oxygen. A carotid arterial cannula and a Swan-Ganz catheter were inserted for hemodynamic monitoring. Pigs in groups 1 and 2 were then allowed to breathe spontaneously and groups 3 and 4 were mechanically ventilated. After obtaining a stable state, as judged by cardiovascular and respiratory parameters, the pigs were infused intravenously with cocaine hydrochloride (0.8 mg/kg/min) until the time of cardiac arrest. Respiratory and cardiovascular parameters, blood temperature, and sodium and potassium levels were monitored. The times of occurrence of respiratory arrests (RA), cardiac arrests (CA), and convulsions were recorded. Our results showed that RA is the primary cause of death in spontaneously breathing pigs and that mechanical ventilation significantly delayed the occurrence of CA (p < 0.05). Significant decreases in cardiac output, mean blood pressure, and heart rate as well as significant increases in systemic and pulmonary vascular resistances, central venous and pulmonary wedge pressures, and blood K+ levels were noted in mechanically ventilated pigs (p < 0.05). Variable hemodynamic responses were noticed in spontaneously breathing pigs. Our results also showed that no significant changes occurred in blood catecholamine levels when compared with baseline values associated with the infusion of toxic doses of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340705 TI - Creatine kinase isoenzyme MB may be elevated in healthy young women after submaximal eccentric exercise. AB - Elevations in serum creatine kinase isoenzyme MB (CK MB) after exercise may be of clinical importance for the diagnosis of myocardial infarction. However, CK MB has been observed to increase after exercise in highly trained endurance runners. No data exist relating to the effect of exercise in a heterogeneous female population with regard to CK MB. The purpose of the present investigation was to determine whether an elevation in serum CK MB can be measured in women (heterogeneous for aerobic capacity, estradiol, and lean body mass) and to make a preliminary analysis of the relationships of postexercise serum CK MB concentration and CK activity, estradiol, lean body mass, and peak oxygen consumption. Lean body mass and peak oxygen consumption were measured for 15 college-age women (19 to 29 years) after the performance of a stepping exercise for 40 minutes at 70% of peak oxygen consumption to elicit the efflux of intramuscular enzymes. Serum CK MB concentration, CK activity, and estradiol level were measured before exercise and 24 and 48 hours after exercise. Serum estradiol level was also measured immediately after exercise. Four of the 15 subjects had elevations in CK MB concentrations ranging from 18.4 to 101.2 micrograms/L, many times the upper normal limit (4.7 micrograms/L). All subjects with high serum CK MB concentrations had high CK activity, and the two measures were significantly related (p < 0.01) in the postexercise period. It was concluded that exercise can cause large elevations in serum CK MB in some women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340706 TI - Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis. AB - We measured concentrations of defensins (human neutrophil peptides) in the plasma of healthy volunteers and patients with sepsis and meningitis. When a sensitive enzyme immunoassay was used, defensins were detected in plasma samples from 13 of 24 healthy blood donors, with a mean +/- SD of 42 +/- 53 ng/ml. Defensin levels in plasma samples from seven patients with sepsis at the onset of disease ranged from 900 ng/ml to 170,000 ng/ml. In 10 patients with meningitis in the initial phase of disease, plasma defensin concentrations ranged from 120 ng/ml to 910 ng/ml. Defensin concentrations in the plasma of both patient groups were significantly higher than those in healthy blood donors (p << 0.01), and patients with sepsis had higher defensin levels than patients with meningitis (p < 0.01). Defensin levels were significantly (p < 0.01) lower after the beginning of specific antibiotic therapy. Defensin concentrations in the plasma of patients with sepsis and meningitis correlated only weakly (r = 0.38) with blood neutrophil count. In vitro studies of defensin added to plasma indicated that all defensin was bound to plasma proteins. At high concentrations (1000 micrograms/ml), defensins caused precipitation of plasma proteins. Because plasma defensin levels may reflect neutrophil activation at sites of infection and inflammation, studies of the clinical utility of defensin ELISA are indicated. PMID- 8340707 TI - Gender differences in hepatic induction and inhibition of theophylline pharmacokinetics and metabolism. AB - This investigation examined whether or not a gender-related effect on theophylline pharmacokinetics and metabolism exists in smoking and nonsmoking subjects with and without the concurrent administration of cimetidine. With a crossover design, 28 healthy men and premenopausal women (14 in each group) were administered intravenous aminophylline before (phase 1) and during (phase 2) a 10 day course of cimetidine, 300 mg four times a day. Statistically significant gender- and smoking-related effects were seen for theophylline half-life and clearance in phase 1, but only the smoking effect was statistically significant for these pharmacokinetic parameters in phase 2. Urinary metabolite excretion patterns demonstrated a greater percentage of excretion of 3-methylxanthine in female smokers than in male smokers in phase 1. Time-averaged urinary clearance of 1,3-dimethyluric acid was greater in female smokers than in male smokers. In phase 2, a significant reduction in the clearance of 1,3-dimethyluric acid was noted in female smokers but not in any other group. The results of our investigation suggest that a significant difference in the pharmacokinetics of theophylline exists that is related to gender and smoking status. Theophylline metabolism also seems to vary according to these factors. Administration of cimetidine results in a significant reduction in clearance of theophylline and abolishes the gender differences but not the smoking differences. PMID- 8340708 TI - Do antiphospholipid autoantibodies modulate the physiological function of cell membrane phospholipids? PMID- 8340709 TI - Protecting the rights of conscience of health care providers. PMID- 8340711 TI - Qui tam litigation. A new forum for prosecuting false claims against the government. PMID- 8340710 TI - On a decision-making paradigm of medical informed consent. PMID- 8340712 TI - Qui tam actions. Are government employees proper qui tam plaintiffs? PMID- 8340713 TI - Application of qui tam to the quality of health care. PMID- 8340714 TI - RU-486: legal and policy issues confronting the Food and Drug Administration. PMID- 8340715 TI - A randomized clinical trial of manual therapy and physiotherapy for persistent back and neck complaints: subgroup analysis and relationship between outcome measures. AB - OBJECTIVE: To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints. The second objective was to determine the correlation between three important outcome measures used in this trial. DESIGN: Randomized clinical trial (subgroup analysis). SETTING: Primary health care in the Netherlands. PATIENTS: Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr. INTERVENTIONS: At the discretion of the manual therapists, physiotherapists and general practitioners. Physiotherapy consisted of exercises, massage and physical therapy (heat, electrotherapy, ultrasound, shortwave diathermy). Manual therapy consisted of manipulation and mobilization of the spine. Treatment by the general practitioner consisted of drugs (e.g., analgesics), advice about posture, home exercises and (bed)rest. Placebo treatment consisted of detuned shortwave diathermy (10 min) and detuned ultrasound (10 min). MAIN OUTCOME MEASURES: Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients. RESULTS: Improvement in the main complaint was larger with manual therapy (4.3) than with physiotherapy (2.5) for patients with chronic conditions (duration complaint of 1 yr or longer). Also, improvement in the main complaint was larger with manual therapy (5.5) than with physiotherapy (4.0) for patients younger than 40 yr (both were measured after 12-mo follow-up). Labeling of patients by the treating manual therapists as "suitable" or "not suitable" for treatment with manual therapy did not predict differences in outcomes. Generally, there was a moderate to strong correlation between the three outcome measures, although a considerable number of patients gave a relatively low score for perceived benefit, while the research assistant gave a high improvement score for the main complaint and physical functioning. CONCLUSIONS: The subgroup analysis suggests better results of manual therapy compared to physiotherapy in chronic patients (duration of present complaints of 1 yr or longer) and in patients younger than 40 yr old). Differences for other subgroups were less clear. The explorative findings of these subgroup analyses have to be investigated in future research. PMID- 8340716 TI - Reactivity of leg alignment to articular pressure testing: evaluation of a diagnostic test using a randomized crossover clinical trial approach. AB - OBJECTIVE: A study was undertaken to assess the reliability of detecting leg alignment changes (reactivity) and to determine if the observed leg alignment reactivity can be attributed to a rotatory articular pressure challenge. DESIGN: Prospective double-blind crossover trial of a diagnostic test. SETTING: Laboratory: Center for Technique Research. PARTICIPANTS: Forty-two chiropractic college students, faculty and staff. INTERVENTIONS: A standardized force of 2 or 3 kg was applied with a 1 cm2 rubber-tipped pressure algometer on the lateral aspect of the T3-T7 spinous processes and the posterior aspect of the lateral masses of C1. MAIN OUTCOME MEASURES: Leg alignment reactivity: an increase in leg alignment discrepancy (yes or no) following a diagnostic intervention. RESULTS: The reliability for detecting leg alignment reactivity was poor: on average, Kappa = 0.05 in the thoracics and 0.06 at C1. On average, the attributable risk of leg alignment reactivity (pressure test risk--sham test risk) was less than 4%. In many cases, the sham rate was greater than the pressure test rate. CONCLUSIONS: For the population investigated, leg alignment reactivity to rotatory pressure testing can, in the majority of cases, be attributable to background noise. This procedure was not found to be viable for identifying vertebrae for adjustment. Further research with different subject populations, regions of investigation, leg alignment measurement techniques and vertebral challenge techniques are indicated. PMID- 8340717 TI - A model for developing standards of care of the chiropractic paraprofessional by task analysis. AB - BACKGROUND: This report is an examination of the demographics of currently employed chiropractic paraprofessionals, including a compilation and verification of a job analysis. Despite the increasing sophistication and accountability of the chiropractic practice, the chiropractic assistant has not maintained a parallel level of maturity. METHODS: Three data-gathering instruments were employed: a) a general survey was used to gather demographics; b) a program for developing a curriculum (DACUM) was used to develop a job analysis; and c) a survey was used to verify tasks and duty areas developed by the DACUM meetings. RESULTS: Demographically, chiropractic paraprofessionals are people with a wide variety of training and duties. Verification surveys of the DACUM model yielded no new tasks or duty areas and assigned relevance to all the tasks listed in the DACUM grid. CONCLUSIONS: No uniform standard of training or competency testing now exists for the chiropractic paraprofessional. The DACUM grid may serve as a useful model for developing a standard of training or competency. PMID- 8340718 TI - Interrelationship between plasma potassium concentration, pulmonary ventilation and electrocardiographic change during and after highly intense exercise. AB - OBJECTIVE: The purpose of this investigation was to induce elevated plasma concentrations of potassium (K+) efflux from active muscle cells during intense muscular exercise. The relationship between K+, pulmonary ventilation (VE) and EKG changes, specifically T-wave amplitude, is presently controversial. DESIGN: Repeated measures design. SETTING: Human performance laboratory. PARTICIPANTS: Twelve volunteer trained recreational cyclists (10 males, mean age 31.9 +/- 7.4, and 2 females, mean age 27.5 +/- 0.7, mean VO2max 571.2 +/- 6.4 ml.kg.min-1). OUTCOME MEASURE: Subjects performed 10 min of pedaling at 90 rpm, yielding a power output of 45 W.min-1 on a mechanically braked cycle ergometer as a warm-up. Each exercise stage was 2 min in duration, beginning at 135 W and increased by 45 W thereafter until voluntary exhaustion. Respiratory gas exchange measures were obtained every 10 sec. Venous blood samples for K+ and lactate (LA-) determination were drawn at rest, at the end of stage 2, all subsequent stages, and during 3 and 10 min of recovery. EKG recordings were concurrent with venous sampling. RESULTS: Statistical analyses for VE vs. K+, respiratory exchange ratio (RER) vs. K+ and RER vs. LA- revealed neither significant change nor an associative relationship from stages 1-3. However, stages 4-8 were statistically significant (p < .05) and highly correlated. No relationship was found between K+ change and T-wave amplitude during exercise or recovery. CONCLUSION: These data indicate a strong relationship between selected respiratory gas exchange measures and K+ during intermediate to highly intense exercise. PMID- 8340719 TI - Compartment syndrome and shin splints of the lower leg. AB - OBJECTIVES: The objective of this article is to review and categorize the current knowledge on compartment syndromes (CS) and shin splints (SS), with specific importance relegated to the diagnosis, differential diagnosis and management of these conditions. DATA SOURCES: The bibliographic data sources reviewed are limited to the English language and human content and are from medical and scientific journals, as well as chiropractic and medical texts. A mini-Medline version of Index Medicus was utilized. Terms for indexing included compartment syndromes, shin splints and stress fractures. The bibliographies of the journals selected were then evaluated and, where appropriate, the specific journal or text references regarding diagnosis and management were then reviewed. This information was then included in this article, where useful, to further clarify or reference statements made. CONCLUSION: Differential diagnosis of the acute CS from chronic CS and SS requires clinical methods and imaging procedures. The pathogenesis of the acute CS of the lower leg is associated with external pressure or internal hemorrhage. If the tissue pressure were to rise above 30-40 mm Hg for 4-12 h, irreversible muscular damage would result. Emergency surgical intervention is the only appropriate form of treatment in acute CS. In chronic CS, where elevated pressures exist on a transient basis, influenced by activity, conservative management procedures are felt to be effective. However, if these methods are not helpful, surgical intervention may be necessary. The etiology of pain associated with SS is not associated with compartmental pressure elevations, but rather, results from periostitis occurring along the tibia caused by muscular and tendinous strain associated with inflammation. Conservative management is most appropriate for this disorder, with surgical intervention being an uncommon treatment approach. Although clinical findings are useful in the diagnosis of these disorders, fluid pressure findings may be necessary to fully differentiate acute CS from other disorders. Up until recently, common methods of obtaining pressure measurements of compartments included the use of a needle manometer. More recently, however, a hand-held miniature fluid pressure monitor has been developed that produces reproducible measurements of interstitial fluid, making testing potentially practical for the clinician. PMID- 8340720 TI - Osteochondroma of the knee. AB - This article discusses a case of osteochondroma suffered by a female patient. The typical clinical and radiographic signs and symptoms are presented. Osteochondromas may be pedunculated or sessile. Malignant transformation ranges from 1% for solitary lesions to 20% for hereditary multiple exostoses. If transformation occurs, chondrosarcoma usually develops. Most lesions are asymptomatic and require no treatment. PMID- 8340721 TI - Temporomandibular disorder associated with sacroiliac sprain. AB - A case of the external derangement-type temporomandibular disorder (TMD), temporarily relieved following chiropractic sacro-occipital technique (SOT) treatment, including SOT category II blocking to reduce sacroiliac sprain, is presented. Symptom exacerbation midway through the course of treatment followed additional dental work; symptom remission followed additional SOT treatment. Freedom from symptoms is maintained with a 3-wk treatment interval. There appears to be a cause-effect relationship between external derangement-type TMD and sacroiliac sprain. Concurrent, coordinated chiropractic and dental treatments may improve the success rate of TMD resolution. PMID- 8340722 TI - Administration in chiropractic education. PMID- 8340723 TI - Muscle scanning: the 18% solution. PMID- 8340724 TI - Metastatic testicular seminoma of the cervicothoracic spine. PMID- 8340725 TI - The effect of spinal manipulation on pain and prostaglandin levels in women with primary dysmenorrhea. PMID- 8340726 TI - Line drawing analyses of static cervical x ray used in chiropractic. PMID- 8340727 TI - Editorial: chiropractic magazines. PMID- 8340728 TI - Respiratory and cardiovascular adjustments during exercise of increasing intensity and during recovery in thoroughbred racehorses. AB - A new design of flowmeter is described and used in a comprehensive study of the respiratory and cardiovascular adjustments that occur during a standardised exercise test in Thoroughbred horses. The flowmeter system and associated lightweight, fibreglass mask (total mass, 0.7 kg) have a maximum dead space of 500 ml and negligible resistance to airflow. They have no systematic effect on blood gases and, together with a rapidly responding mass spectrometer, enable an accurate computation of gas exchange to be performed together with breath-by breath determination of other respiratory variables. At the highest level of exercise (12 ms-1 on a 3 degrees incline), the rate of oxygen uptake (VO2) and carbon dioxide production (VCO2) increased to 29.4 times and 36.8 times their resting values, respectively. Respiratory minute volume (VE) increased to 27.0 times its resting value, with respiratory frequency (fR) making the major contribution at the walk and trot. However, with increasing cantering speeds, fR changed little as it was locked in a 1:1 fashion to stride frequency, and tidal volume (VT) then made the major contribution to the increase in VE. The ratio of ventilatory dead space (VD) to VT in resting horses was lower than that previously reported in the literature and this could be the result of the different respiratory recording systems that were used. There was a close relationship between VT and stride length at increasing cantering speeds. Despite the fact that alveolar ventilation (VA) was well matched to VO2, there was a significant reduction in arterial PO2 (PaO2) when the horses cantered at 8 ms-1 and this eventually fell to 34% below the resting value. The present data tend to support the idea that VA/Vb (where Vb is cardiac output) inequalities are important in causing this hypoxaemia. However, the reduction in PaO2 was more than compensated for by an increase in haemoglobin concentration, [Hb], so the concentration of oxygen in the arterial blood (CaO2) was significantly above the resting value at all levels of exercise. Both lactate concentration and PaCO2 increased during exercise, causing substantial reductions in pH of both arterial and mixed venous blood. This would have inevitably shifted the oxygen equilibrium curve of the Hb to the right, desaturating the arterial blood and thus exacerbating the effect of the hypoxaemia, as would the almost 4 degrees C rise in blood temperature. The tight respiratory/locomotor linkage might prevent the acidosis and hyperthermia having the stimulatory effects on VE that they have in humans at high work loads.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8340729 TI - Bioenergetic and kinematic consequences of limblessness in larval Diptera. AB - We report the cost of transport and kinematics of terrestrial locomotion by larval blowflies (Protophormia terraenovae, Diptera: Calliphoridae). We contrast inter- and intra-individual methods for estimating minimum cost of transport (MCOT) and the relationship between speed, contraction frequency and distance traveled per contraction. The minimum cost of transport calculated from intra individual data is 2297 +/- 317 J kg-1 m-1 (S.E.M.) and the MCOT calculated from inter-individual comparisons is statistically indistinguishable at 1910 +/- 327 J kg-1 m-1. These values are almost ten times higher than the predicted value for a similar-sized limbed arthropod. Fly larvae travel by repeated peristaltic contractions and individual contractions cost about the same amount as individual strides in limbed insects. Both contraction frequency and distance traveled per contraction increase linearly with speed. Doubling the contraction frequency or the distance traveled per contraction approximately doubles speed. The cost of transport in fly larvae is among the highest recorded for terrestrial locomotion, confirming the suggestion that biomechanical and kinematic properties of limbless organisms with hydraulic skeletons lead to very high costs of transport. PMID- 8340730 TI - Effect of temperature on central chemical control of ventilation in the alligator Alligator mississippiensis. AB - Central chemoreceptor function was assessed in unanesthetized alligators, Alligator mississippiensis, at body temperatures of 15, 25 and 35 degrees C. Two experiments were performed. In the first experiment, the fourth ventricle was perfused with mock cerebrospinal fluid (CSF) solutions of different pH values (7.1-7.9). Changes in pulmonary ventilation were evaluated with a pneumotachograph and arterial pH (pHa) was measured. Perfusion with low-pH solutions increased ventilation and arterial pH. Perfusion with high-pH solutions decreased ventilation and arterial pH. Mock CSF pH had a greater effect at higher temperatures. In the second experiment, the relative contributions of central and peripheral chemoreceptor drive to breathing were evaluated using hypercapnic gas mixtures to stimulate both central and peripheral chemoreceptors. Hypercapnia caused an increase in ventilation which was larger at higher temperatures. To stimulate only the peripheral chemoreceptors, the same hypercapnic gas mixtures were applied while the CSF pH of the fourth ventricle was kept constant by perfusion with a mock CSF solution. This reduced significantly the ventilatory response induced by hypercapnia. These data indicate that, regardless of the temperature, central chemoreceptors play a major role in the ventilatory regulation of the alligator. The change in pHa with temperature is compatible with the alphastat hypothesis. PMID- 8340731 TI - The physiology of bottlenose dolphins (Tursiops truncatus): heart rate, metabolic rate and plasma lactate concentration during exercise. AB - Despite speculation about the swimming efficiency of cetaceans, few studies have investigated the exercise physiology of these mammals. In view of this, we examined the physiological responses and locomotor energetics of two exercising adult Tursiops truncatus. Oxygen consumption, heart rate, respiratory rate and post-exercise blood lactate concentration were determined for animals either pushing against a load cell or swimming next to a boat. Many of the energetic and cardiorespiratory responses of exercising dolphins were similar to those of terrestrial mammals. Average heart rate, respiratory rate and oxygen consumption for dolphins pushing against a load cell increased linearly with exercise levels up to 58 kg for a female dolphin and 85 kg for a male. Oxygen consumption did not increase with higher loads. Maximum rate of oxygen consumption (VO2max) ranged from 19.8 to 29.4 ml O2 kg-1 min-1, which was 7-11 times the calculated standard metabolic rate (VO2std) of the dolphins. Blood lactate concentration increased with exercise loads that exceeded VO2max. The maximum lactate concentration was 101.4 mg dl-1 (11.3 mmol l-1) for the male, and 120.6 mg dl-1 (13.6 mmol l-1) for the female. When swimming at 2.1 m s-1, heart rate, respiratory rate and post exercise blood lactate concentration of the dolphins were not significantly different from values at rest. The cost of transport at this speed was 1.29 +/- 0.05 J kg-1 min-1. The energetic profile of the exercising bottlenose dolphin resembles that of a relatively sedentary mammal if the exercise variables defined for terrestrial mammals are used. However, the energetic cost of swimming for this cetacean is low in comparison to that of other aquatic and semi-aquatic mammals. PMID- 8340732 TI - Sun and skin damage. PMID- 8340733 TI - Scleroderma--clinical aspects. PMID- 8340734 TI - Intravenous immunoglobulin treatment in cytopenic haematological disorders. PMID- 8340735 TI - Anaphylatoxins in dilated cardiomyopathy. AB - OBJECTS: The aim of the study was to investigate the possible relationship between activation of complement system and thromboembolic complications in dilated cardiomyopathy (DCMP). METHODS: The plasma C3a and C5a concentrations were determined by radioimmunoassay measurement (Amersham International, UK) in 23 patients with DCMP, 9 with hypertrophic cardiomyopathy (HCMP) and 11 healthy volunteers. RESULTS: The mean C3a concentration was significantly higher in DCMP patients (572 +/- 55 ng ml-1) compared with hypertrophic cardiomyopathy (344 +/- 30 ng ml-1) and with healthy controls (294 +/- 43 ng ml-1) (P < 0.001). There were no significant correlations for C5a concentrations in this group. Mean C3a concentration in DCMP patients with thromboembolic complications (736 +/- 95 ng ml-1) was also significantly higher compared with DCMP patients without these complications (344 +/- 14 ng ml-1) (P < 0.001). CONCLUSIONS: We conclude that anaphylatoxins may play a role in the pathogenesis of thromboembolic complications. PMID- 8340736 TI - Effect of promethazine on lumbar vertebral bone mass in postmenopausal women. AB - OBJECTIVES: Work in mice suggests that the age-related loss of bone mineral noted in that species is caused by an intrinsic defect in a haematopoietic cell population which results directly or indirectly in increased bone resorption. This age-related loss of bone mineral is prevented or reversed by well-tolerated doses of promethazine HCL. The present study was undertaken to determine if promethazine would retard or reverse bone loss in postmenopausal women. DESIGN: Postmenopausal women whose spine (L2 to L4) bone mineral content (BMC) was two standard deviations below young normal values were assigned randomly to receive calcium or promethazine and calcium daily. Subjects who had been taking oral oestrogen for more than 4 years also were assigned randomly but independently to the calcium or promethazine groups. SETTING: All subjects were seen in the out patient clinic of the Department of Medicine, School of Medicine, University of California, Los Angeles. SUBJECTS: Healthy, ambulatory postmenopausal females were recruited by word of mouth and by advertisement from the local community. Fifty-four subjects completed the first 6 months of the study and 43 completed 30 months. INTERVENTIONS: The subjects were assigned randomly to receive 1000 mg calcium daily or promethazine 50 mg and calcium 1000 mg daily throughout the period of the study. MAIN OUTCOME MEASURES: Bone mineral content of the lumbar vertebrae (L2 to L4) was determined by dual photon densitometry every 6 months. Dorsolumbar spine X-rays were obtained yearly and at the completion of the study to detect new compression fractures. RESULTS: In the groups not taking oestrogen, BMC decreased at the rate of 1.53% year-1 in the group given only calcium; in contrast, BMC increased at 3.22% year-1 in the group given promethazine and calcium (P < 0.001). Among the women taking oestrogen, increases in mean BMC were noted in both groups, but those taking promethazine and calcium had a greater rate of increase than observed in the group taking only calcium (5.62% vs. 1.97% per year-1, P < 0.001). CONCLUSIONS: These results suggest that promethazine can induce a modest increase in vertebral BMC in postmenopausal women who are not taking oestrogen and greater increases in those who are. PMID- 8340737 TI - No evidence of mitochondrial abnormality in skeletal muscle of patients with iron deficient anaemia. AB - OBJECTIVES: Patients with iron deficiency anaemia complain of decreased exercise capacity. We asked whether this is due to defective oxidative ATP synthesis in skeletal muscle as a consequence of reduced blood oxygen content and/or intrinsic mitochondrial abnormalities. DESIGN: We used 31P magnetic resonance spectroscopy to examine skeletal muscle bioenergetics in iron-deficient patients and in age- and sex-matched controls. SETTING: The patients were recruited from the primary care population. SUBJECTS: We studied seven symptomatic female iron-deficient patients (aged 32-70 years) with haemoglobin (Hb) concentration, [Hb], 8.0 g dl 1. Six had menorrhagia, the cause in the seventh patient remained undiagnosed. Results were compared with those of 8 healthy female controls (aged 25-48 years) with mean [Hb] 13.7 g dl-1. RESULTS: The right calf muscle was by studied 31P magnetic resonance spectroscopy in a 1.9 T super-conducting magnet. We measured the intracellular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), adenosine triphosphate (ATP) and the intracellular pH at rest, during plantar flexion exercise and during recovery from exercise. Exercise duration was reduced in the patients, yet end-exercise PCr/(PCr+Pi) was higher and adenosine diphosphate (ADP) lower than in controls. After exercise, initial PCr recovery was slowed but this was probably because of the lower cytosolic ADP concentration. CONCLUSIONS: Mitochondrial ATP synthesis was not limited by oxygen supply or an intrinsic mitochondrial defect. Therefore, the reduced exercise capacity seen in iron deficiency could be due to central causes and not to skeletal muscle metabolic abnormalities. PMID- 8340738 TI - Drug expectations and drug choices of hospital physicians. AB - OBJECTIVES: To assess whether differences in drug choices of hospital physicians are related to differences in the underlying decision-making process. DESIGN: A survey study was conducted addressing drug choices in six therapeutic fields with existing interprescriber variations; prescribers and non-prescribers of drugs of which the merits were not sufficiently proven (i.e. the 'target drugs') were compared. SETTING: A 1000-bed university hospital in The Netherlands. SUBJECTS: All 85 hospital physicians working in specialities involving one of the selected fields were asked to participate; 72 physicians completed the interviews. MAIN OUTCOME MEASURES: Comparisons were made regarding three elements of the decision making process: (1) the physicians' expectations of the target drugs and frequently used alternatives, (2) the weights attached to the principal treatment aspects, and (3) the extent to which their actual choice is based on these expectations and weights. RESULTS: In three fields, i.e. anti-emetics, vasodilators, and platelet inhibitors, the prescribers of the less desirable target drugs had higher expectations of these drugs in comparison to the non prescribers. In the other therapeutic fields, choosing target drugs was related either to attaching less importance to side-effects and costs, or to attaching less importance to reports from clinical trials. Twenty of the 46 treatment choices of the prescribers of target drugs could not be predicted from their expressed views as opposed to 5 of the 36 choices of the non-prescribers (P < 0.05). CONCLUSIONS: Choosing less desirable drugs is not always related to having too high expectations of the drug. Assigning a different importance to certain aspects of the drug and resorting to decision strategies that do not include the weighing of all pros and cons provide alternative explanations for such treatment choices. PMID- 8340739 TI - Presenting features of monoclonal gammopathies: an analysis of 684 newly diagnosed cases. Cooperative Group for the Study and Treatment of Multiple Myeloma. AB - OBJECTIVES: The clinical, laboratory and radiologic features at diagnosis of 684 newly diagnosed patients with monoclonal gammopathy were revised in order to underline the differences between monoclonal gammopathies of undetermined significance (MGUS) and stage I multiple myeloma (MM). DESIGN: Patients were screened for inclusion in a prospective controlled protocol for treatment of MM. Those having serum or urine monoclonal component (MC) were diagnosed as MM when they demonstrated osteolysis and/or bone marrow plasma cells (BMPC) > 20%; patients not fulfilling these criteria were considered MGUS. SETTING: Patients were recruited from 24 general or university hospitals from the departments of internal medicine, haematology and medical oncology. SUBJECTS: Seven-hundred-and fifty were enrolled between January 1986 and March 1990; 684 (343 MGUS and 341 MM) were able to be evaluated for this study and 78 were stage I MM. INTERVENTIONS: Complete clinical, radiologic and laboratory work-up was carried out at the referral centres. MAIN OUTCOME MEASURES: The main outcome expected was the confirmation that BMPC > 20% could reliably differentiate stage I MM from MGUS. RESULTS: At a median follow-up of 36 months (minimum follow-up: 18 months), MGUS had a lower progression rate to overt MM, longer overall survival and different causes of death than stage I MM. Further differences concerned erythrocyte sedimentation rate (28 vs. 47, P < 0.001), per cent reduction of normal immunoglobulin (86 vs. 60%, P < 0.001), serum MC (1.6 vs. 2.2 g dl-1, P < 0.001) and thymidine kinase level (3.3 vs. 4.5 mU ml-1, P < 0.05). CONCLUSIONS: The study suggests that 20% BMPC can be taken as a safe cut-off point at which to differentiate MGUS from early MM and outlines a few simple parameters which can be of diagnostic aid. PMID- 8340740 TI - Diurnal blood pressure variations in normoalbuminuric type 1 diabetic patients. AB - OBJECTIVE: To test the hypothesis that normoalbuminuric type 1 diabetic patients segregate into groups with normal and elevated ambulatory blood pressure. To evaluate diurnal variation of blood pressure assessed by individual or fixed night-time periods. DESIGN: Cross-sectional study. SETTING: Tertiary referral centre. SUBJECTS: Inclusion criteria for type 1 diabetic patients (n = 33): normal urinary albumin excretion (UAE age < 45 < 20 micrograms min-1), diabetes duration < or = 20 years, age 45 years. Healthy controls (n = 33) were matched for sex and age. MAIN OUTCOME MEASURE: Twenty-four hour, day-time, night-time and night/day ratio of ambulatory blood pressure. RESULTS: Twenty-four-hour blood pressure in diabetic patients did not differ significantly from a normal distribution. The 24-h systolic blood pressure was higher in diabetic patients than in healthy controls (difference: 6 mmHg, 95% confidence interval (CI) from 1 to 10 mmHg, P < 0.05), while no significant differences were found for diastolic values. The 24-h systolic blood pressure in diabetic patients with UAE above the median value (5.8 micrograms min-1) was higher than for those with lower UAE (difference: 7 mmHg, 95% CI from 0.5 to 13 mmHg, P < 0.05). The night/day ratio of diastolic blood pressure based on individual informations of the night period was (mean +/- SD) 80 +/- 6% in diabetic patients and 78 +/- 8% in controls (difference: 2%, 95% CI from -1 to 5%, not significant [NS]). This ratio increase significantly (P < 0.00001) to 90 +/- 5% in diabetes and to 84 +/- 7% in controls if a fixed night period from 22.30 hours to 06.30 hours was assumed. CONCLUSIONS: It was not possible to identify a well-separated group of normoalbuminuric type 1 diabetic patients with elevated ambulatory blood pressure. Values of UAE above the median in diabetic patients are associated with higher ambulatory blood pressure. Assessment of the night/day variation from fixed time-points should be abandoned because this leads to a serious underestimation of the nocturnal reduction in blood pressure. PMID- 8340741 TI - Accuracy of clinical diagnoses in a teaching hospital: a review of 997 autopsies. AB - OBJECTIVES: To analyse the concordance between clinical and autopsy diagnoses. DESIGN: Nine-hundred-and-ninety-seven autopsies were studied comparing the diagnoses of the autopsy requests with those of the death certificates and autopsy reports. The cases were grouped according to the 17 categories of diseases of the International Classification of Diseases (ICD) and the concordance was analysed with the kappa (kappa) coefficient of concordance. SETTING: The Hospital da Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRPUSP), Ribeirao Preto, SP, Brazil. SUBJECTS: The patients autopsied at HCFMRPUSP during the period between 1978 and 1980. MAIN OUTCOME MEASURES: kappa statistics offer an alternative approach to measuring the concordance between clinical and autopsy diagnoses. RESULTS: The kappa-value obtained was equal to 0.601 with a variance of 1.545 x 10(-4) when comparing the clinical diagnoses and the autopsy diagnoses, and equal to 0.661 with a variance of 1.531 x 10(-4) comparing the clinical diagnoses with those obtained after the gross examination. These values are significant at the level of 5%, i.e. there is an overall statistical concordance between clinical and autopsy diagnoses although the value is not absolute (kappa = 1.00). CONCLUSIONS: If autopsies are heeded without bias, they will continue to give important feedback concerning medical diagnosis. PMID- 8340742 TI - Hand abnormalities are strongly associated with the duration of diabetes mellitus. AB - OBJECTIVES: To study the prevalence of hand abnormalities in diabetic patients and to evaluate associations between the hand abnormalities and diabetic variables, ergonomic factors and smoking habits. DESIGN: Cross-sectional study of 100 patients selected at random. Setting. Out-patient clinic, Department of Internal Medicine, Orebro Medical Centre Hospital in Sweden. MAIN OUTCOME MEASURES: Presence and extent of carpal tunnel syndrome (CTS), Dupuytren's contracture (DC), flexor tenosynovitis (FTS), and limited joint mobility (LJM). Duration of diabetes, metabolic control, chronic diabetic complications, blood pressure, ergonomic factors and smoking habits. RESULTS: Carpal tunnel syndrome, DC, FTS and LJM were each present in about 20% of the patients. Hand abnormalities were observed in 50 patients and more than one abnormality was found in 26 of the patients. The hand abnormalities were associated with the duration of diabetes but not with the metabolic control or with other diabetic complications. However, the diabetic complications were associated with bad metabolic control and with the duration of diabetes. Hand abnormalities correlated with heavy manual work but not with smoking habits. Twenty-five of the 50 patients with hand syndromes were disabled to such an extent that surgery was recommended. CONCLUSION: The prevalence of hand abnormalities in diabetic patients is high and increases with the duration of diabetes. In many cases patients with hand abnormalities can be helped by surgery. PMID- 8340744 TI - Correspondence between screening and intra-arterial blood pressures in young men with borderline hypertension. AB - OBJECTIVES: To evaluate the screening blood pressure (BP) for identification of individuals with a mild but persistent elevation of BP referred to as borderline hypertension (BH). DESIGN: Based on screening data from approximately 10,500 men at a military enlistment centre in 1987; an unbiased population sample of young men were recruited. Blood pressure follow-up and investigation of anthropometric and metabolic data were made at Ostra Hospital. SUBJECTS: Men aged 19.8 years (range 17-28) were screened. Three hundred and six were found to have elevated BP (systolic BP (SBP) > 145 mmHg and/or diastolic BP (DBP) > or = 85 mmHg). Of these, 179 were re-examined after 1-3 years, by which time three individuals exceeded the limits for established hypertension and 80 fulfilled the BP criteria for BH (in two out of two blood pressure measurements). Fifty-four of these BH individuals were investigated with intra-arterial (i.a.) BP measurements. A normotensive control (NC) group (SBP 110-130 and DBP 60-80 mmHg; n = 20) from the same population was examined concomitantly. RESULTS: At screening, at the 2-year clinic follow-up and again during the intra-arterial recording, SBP was significantly different in BH vs. NC. With DBP an increasing difference between the groups was observed with time. There were highly significant correlations between screening and 2-year clinic BP (r = 0.72, P < 0.001; n = 74) and screening and i.a. BP (r = 0.57, P < 0.001; n = 74). CONCLUSIONS: These data show that there is a correspondence between BP at the screening procedure and i.a. BP measured 2 years later, indicating that the screening procedure is a useful way of identifying young men with mild but persistent BP elevation. This interpretation is supported by metabolic and biochemical differences between the groups. PMID- 8340743 TI - Effects of age, sex, season and diet on serum ionized calcium, parathyroid hormone and vitamin D in a random population. AB - OBJECTIVES: To study the influence of age, sex, season and diet on calcium status in normal subjects. DESIGN: A random population study. Setting. Institutional clinic for large population studies. SUBJECTS: The subjects were drawn randomly from the Danish Civil Registration System and represented a random sample of the background population in the area. The sample comprised 127 subjects (54 men and 73 women, aged 35-65 years). MAIN OUTCOME MEASURES: The effects of age, sex, season and diet on parathyroid hormone (PTH),1,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25-OHD). RESULTS: There was no statistical significant difference for the serum concentrations of ionized calcium, PTH, 1,25(OH)2D and 25-OHD between the two sexes, nor any influence by age in either sex, in contrast to serum phosphate, which declined significantly in men (P < 0.05), but tended to increase in women. Serum PTH (P < 0.009) showed seasonal fluctuations, whereas serum concentrations of 1,25(OH)2D, 25-OHD, ionized calcium, phosphate and magnesium remained stable throughout the year. Dietary intake of calcium and vitamin D were not related to any serum variables. CONCLUSIONS: In healthy subjects differences between the two sexes exist regarding phosphate metabolism. Serum PTH shows seasonal fluctuations. PMID- 8340745 TI - Lipoprotein abnormalities in hypertriglyceridaemic patients on long-term haemodialysis. AB - OBJECTIVES: To analyse by ultracentrifugation in a zonal rotor the plasma lipoproteins in hypertriglyceridaemic patients on long-term haemodialysis. DESIGN: Case-control study. SETTING: Tertiary referred care centre. SUBJECTS: Ten consecutive hypertriglyceridaemic patients on haemodialysis and 12 consecutive healthy controls. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein cholesterol concentrations, lipoprotein physical properties and compositions, apolipoprotein concentrations. RESULTS: Hypertriglyceridaemia in patients undergoing haemodialysis is characterized by an increased amount of small and slow floating very-low density lipoproteins (VLDL), higher concentrations of intermediate density lipoproteins (IDL) and small and dense low-density lipoprotein (LDL) particles; reduced levels of high-density lipoproteins (HDL), in particular of HDL2. The lipoprotein composition of such patients indicates reduced cholesterol ester and increased triglyceride content. Compared to controls, they have lower levels of plasma apolipoprotein A-I and A-II and higher B, C-II, C-III and E values. CONCLUSIONS: The lipoprotein abnormalities observed in hypertriglyceridaemic patients undergoing haemodialysis have recently been associated with an increased incidence of vascular complications and may in part explain the high incidence of vascular disease reported in these subjects. PMID- 8340746 TI - Reactivation of chronic hepatitis C after withdrawal of immunosuppressive therapy. AB - A patient with immune-mediated thrombocytopenia (ITP) and chronic hepatitis C virus (HCV) infection for 11 years was given immunosuppressive treatment because of an activation of his ITP. After 6 weeks of treatment with cyclophosphamide, cyclosporin A and cortisone the patient decided not to continue taking his medication. One month later he was readmitted to hospital due to fever, cough and jaundice. Clinical investigation revealed his condition to be caused by an activation of his HCV infection. It is concluded that, in parallel to the situation in hepatitis B, immunosuppressive treatment of patients with HCV infection may lead to increased viral replication, resulting in severe liver damage when immunocompetence is regained. PMID- 8340747 TI - Long QT syndrome with insulin-dependent diabetes mellitus: contiguous gene syndrome on chromosome 11p. AB - Long QT syndrome (Romano-Ward syndrome) and insulin-dependent diabetes mellitus (IDDM) have been documented as being linked with gene(s) on chromosome 11p although concurrence of the two disorders has not been reported. Our case is a 13 year-old boy with Romano-Ward syndrome accompanied by IDDM. The long QT syndrome seemed to be transmitted in an autosomal-dominant mode because the Q-T intervals of his father and paternal grandfather were longer than normal. There was no family member with an abnormally high level of blood glucose except the patient. The human leucocyte antigen (HLA) haplotypes of the patient and the father were DR4/DR9 and DR2/DR9, respectively. This study suggests that in our patient IDDM, as well as Romano-Ward syndrome, is linked with chromosome 11p in the presence of HLA-DR4. The results support the previous study that chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. PMID- 8340748 TI - Disseminated Mycobacterium malmoense infection in a patient with chronic granulocytic leukaemia. AB - Mycobacterium malmoense is an atypical mycobacterium previously isolated from lymph nodes in children and from adults with pulmonary disease. Disseminated infection is extremely rare and bone marrow involvement has never previously been described. We report a patient with chronic granulocytic leukaemia and persistent fever with granuloma in the bone marrow due to disseminated M. malmoense infection. The patient initially received treatment with isoniazid, ethambutol and rifampicin with clearance of mycobacteria in the bone marrow and clinical improvement. Sensitivity in vitro was established for streptomycin, amikacin, ethambutol and rifabutin. The patient eventually expired as a result of progressive respiratory failure from other opportunistic infections. At autopsy staining of samples from lung parenchyma revealed fungal hyphi but staining for Pneumocystis carinii and myobacteria were negative. PMID- 8340749 TI - C1 esterase inhibitor gene expression in rat Kupffer cells, peritoneal macrophages and blood monocytes: modulation by interferon gamma. AB - Kupffer cells (KC) represent the main part of the tissue macrophages. Beside phagocytosis of particulate material, involvement of KC in immunological and inflammatory reactions has been supposed. As C1 esterase inhibitor (C1-INH) is a serine protease inhibitor involved in such processes, the aim of this work was to study C1-INH synthesis in KC and, by comparison, in peritoneal macrophages (PM) and blood monocytes (MC) of the rat. C1-INH synthesis was studied on the protein level by biosynthetic labeling, immunoprecipitation, and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis, and on the RNA level by Northern blotting of total RNA or by in situ hybridization. KC were found to express C1 INH gene spontaneously. C1-INH synthesis represents 1.3 +/- 0.2% of total protein synthesis at day 1 of culture and the absolute amount each cell synthesis remains constant during the whole time in culture. Transcripts of C1-INH were detected both in freshly isolated and in cultured KC. In contrast, spontaneous C1-INH gene expression was not detectable in freshly isolated PM, but only in cultured PM. In MC, C1-INH was not detectable at any time, whatever. Treatment of the cells with interferon gamma increased C1-INH synthesis in KC and in PM and caused an induction of C1-INH synthesis in MC. The results suggest that constitutive C1-INH synthesis is a functional marker for mature tissue macrophages. PMID- 8340750 TI - Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation. AB - The c-fes protooncogene is expressed at high levels in the terminal stages of granulocytic differentiation, but so far no definite function has been attributed to the product of this oncogene. To tackle this problem, the c-fes protooncogene expression has been inhibited in HL60 cells, and fresh leukemic promyelocytes of acute promyelocytic leukemia have been induced to differentiate with retinoic acid (RA) and dimethylsulfoxide (DMSO). Inhibition was obtained by incubating the cells with a specific c-fes antisense oligodeoxynucleotide. It was observed that the cells, rather than differentiating, underwent premature cell death showing the morphological and molecular characteristics of apoptosis. This process was inhibited by granulocyte and granulocyte/macrophage colony-stimulating factor, but not by interleukin 3 (IL-3), IL-6, or stem cell factor. Our present results demonstrate that the loss of cell viability that occurs during the in vitro differentiation of myeloid cells, after the complete inhibition of the c-fes gene product and treatment with RA-DMSO, is due to activation of programmed cell death. It is concluded that a possible role of the c-fes gene product is to exert an antiapoptotic effect during granulocytic differentiation. PMID- 8340751 TI - Suppressible and nonsuppressible autocrine mast cell tumors are distinguished by insertion of an endogenous retroviral element (IAP) into the interleukin 3 gene. AB - After v-H-ras expression, the interleukin 3 (IL-3)-dependent PB-3c mast cells progress in vivo to two different classes of IL-3 autocrine tumors. Class I tumors show a germline configuration of the IL-3 gene and represent more than 90% of tumors analyzed so far. Somatic cell fusion of class I tumor lines with the nontumorigenic parental PB-3c resulted in loss of oncogenic IL-3 expression by a posttranscriptional mechanism with concomitant tumor suppression. Class II tumors arise rarely and contain an insertion in one IL-3 allele. This alteration was linked to enhanced IL-3 gene transcription. For one tumor, the insertion was shown to be an endogenous retroviral element (intracisternal A-particle). Cell hybrids of class II tumors with PB-3c remained IL-3 independent, expressed IL-3, and formed tumors rapidly. These results suggest that the v-H-ras oncogene synergizes with a recessive and a dominant lesion in class I and II tumors, respectively, both of which lead to the autocrine production of IL-3. PMID- 8340752 TI - The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory. AB - The bcl-2 gene product has been shown to prevent apoptotic cell death. We have now investigated the bcl-2 protein expression by resting and activated mature T cell populations. Freshly isolated CD45RO+ T cells within CD4+ and CD8+ subsets expressed significantly less bcl-2 than CD45RO- (CD45RA+) T cells (p < 0.001). When CD45RA+ T cells within both CD4+ and CD8+ subsets were activated in vitro, the transition to CD45RO phenotype was associated with a decrease in bcl-2 expression. Patients with acute viral infections such as infectious mononucleosis caused by Epstein-Barr virus infections or chickenpox, resulting from varicella zoster virus infection, had circulating populations of activated CD45RO+ T cells which also showed low bcl-2 expression. In these patients, a significant correlation was seen between low bcl-2 expression by activated T cells and their apoptosis in culture (r = 0.94, p < 0.001). These results suggest that the primary activation of T cells leads to the expansion of a population that is destined to perish unless rescued by some extrinsic event. Thus the suicide of CD45RO+ T cells could be prevented by the addition of interleukin 2 to the culture medium which resulted in a concomitant increase in the bcl-2 expression of these cells. Alternatively, apoptosis was also prevented by coculturing the activated T lymphocytes with fibroblasts, which maintained the viability of lymphoid cells in a restinglike state but with low bcl-2 expression. The paradox that the CD45RO+ population contains the primed/memory T cell pool yet expresses low bcl-2 and is susceptible to apoptosis can be reconciled by the observations that maintenance of T cell memory may be dependent on the continuous restimulation of T cells, which increases their bcl-2 expression. Furthermore, the propensity of CD45RO+ T cells to extravasate may facilitate encounter with fibroblast-like cells in tissue stroma and thus be an important additional factor which promotes the survival of selected primed/memory T cells in vivo. PMID- 8340753 TI - PECAM-1 is required for transendothelial migration of leukocytes. AB - Platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) is crucial to the process of leukocyte transmigration through intercellular junctions of vascular endothelial cells. A monoclonal antibody to PECAM, or recombinant soluble PECAM, blocks transendothelial migration of monocytes by 70-90%. Pretreating either the monocytes or the endothelial junctions with antibody blocks transmigration. If the endothelium is first activated by cytokines, anti-PECAM antibody or soluble recombinant PECAM again block transmigration of both monocytes and neutrophils. Anti-PECAM does not block chemotaxis of either cell type. Light and electron microscopy reveal that leukocytes blocked in transmigration remain tightly bound to the apical surface of the endothelial cell, precisely over the intercellular junction. Thus, the process of leukocyte emigration can be dissected into three successive stages: rolling, mediated by the selectin class of adhesion molecules; tight adhesion, mediated by the leukocyte integrins and their endothelial cell counter-receptors; and now transmigration, which, based on these studies, requires PECAM-1. PMID- 8340754 TI - A complex of glycoproteins is associated with VpreB/lambda 5 surrogate light chain on the surface of mu heavy chain-negative early precursor B cell lines. AB - Monoclonal antibodies (mAbs) have been made specific for the pre-B cell-specific proteins VpreB and lambda 5 which together form the surrogate light (L) chain. mAbs specific for VpreB protein identified the 16-kD molecule associated on precursor B cell lines with lambda 5 protein as the product of the VpreB gene. Surrogate L chain was detectable even in the absence of mu heavy (H) chain on the surface of early precursor cell lines such as pro-B cell lines where all immunoglobulin (Ig) loci are in the germline configuration, as well as early pre B cell lines where Ig H chain loci are DHJH rearranged in reading frame I or III, which does not allow the expression of a DHJHC mu protein. A complex of glycoproteins (200, 130, 105, and 65-35 kD) was identified as coprecipitated with the Vpreb/lamba 5 surrogate L chain in mu H chain-negative precursor B cell lines. The 130-kD protein was most strongly labeled with iodine and most consistently detected in noncovalent association with surrogate L chain. This protein turned out to be a N-linked glycoprotein with a 100-kD protein core and isoelectric point 5.8, indicating that it is distinct from CD43 and the BP-1/6C3 antigen. The surface deposition of the surrogate L chain in association with the newly identified glycoproteins suggests that the surrogate L chain may function as a receptor even before the association with mu H chain in early precursor B cells. PMID- 8340755 TI - The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. AB - Lymphocytes of melanoma patients can be restimulated in vitro with autologous tumor cells to generate antitumor cytolytic T lymphocytes (CTL). Previous reports have indicated that, when such CTL are obtained from HLA-A2 melanoma patients, they often display broad reactivity on A2 melanoma cell lines. Such antitumor CTL clones, which appeared to recognize the same antigen, were isolated from two patients. We report here the cloning of a cDNA that directs the expression of the antigen recognized by these CTL. This cDNA corresponds to the transcript of the tyrosinase gene. The gene was found to be active in all tested melanoma samples and in most melanoma cell lines. Among normal cells, only melanocytes appear to express the gene. The tyrosinase antigen presented by HLA-A2 may therefore constitute a useful target for specific immunotherapy of melanoma. But possible adverse effects of antityrosinase immunization, such as the destruction of normal melanocytes and its consequences, will have to be examined before clinical pilot studies can be undertaken. PMID- 8340756 TI - CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation. AB - The in vivo administration of certain monoclonal antibodies (mAbs) against the adhesion receptor, CD44, into normal mice induces both a modulation of CD44 from the surface of peripheral lymphocytes, and a concomitant increase in the amount of soluble CD44 in the serum. CD44-negative lymphocytes isolated from anti-CD44 treated mice exhibit normal homing patterns upon adoptive transfer, and are capable of reexpressing CD44 upon activation. The treatment of haptensensitized mice with anti-CD44 mAb inhibits their ability to mount a cutaneous delayed-type hypersensitivity (DTH) response within the first 24 h after hapten challenge. This inhibition reflects a block in both the edema and leukocyte infiltration of the cutaneous site of DTH, whereas the extravasation and accumulation of leukocytes in the draining lymph nodes progress normally. After 72 h, the leukocytes that extravasate into the site of antigen challenge express CD44. These results indicate that CD44 is not necessary for normal leukocyte circulation but is required for leukocyte extravasation into an inflammatory site involving nonlymphoid tissue. PMID- 8340757 TI - Human cord blood cells as targets for gene transfer: potential use in genetic therapies of severe combined immunodeficiency disease. AB - Human cord blood (CB) contains large numbers of both committed and primitive hematopoietic progenitor cells and has been shown to have the capacity to reconstitute the lympho-hematopoietic system in transplant protocols. To investigate the potential usefulness of CB stem and progenitor cell populations to deliver new genetic material into the blood and immune systems, we have transduced these cells using retroviral technology and compared the efficiency of gene transfer into CB cells with normal adult human bone marrow cells using a variety of infection protocols. Using two retroviral vectors which differ significantly in both recombinant viral titers and vector design, low density CB or adult bone marrow (ABM) cells were infected, and committed progenitor and more primitive hematopoietic cells were analyzed for gene expression by G418 drug resistance (G418r) of neophosphotransferase and protein analysis for murine adenosine deaminase (mADA). Standard methylcellulose progenitor assays were used to quantitate transduction efficiency of committed progenitor cells, and the long term culture-initiating cell (LTC-IC) assay was used to quantitate transduction efficiency of more primitive cells. Our results indicate that CB cells were more efficiently transduced via retroviral-mediated gene transfer as compared with ABM derived cells. In addition, stable expression of the introduced gene sequences, including the ADA cDNA, was demonstrated in the progeny of infected LTC-ICs after 5 wk in long-term marrow cultures. Expression of the introduced ADA cDNA was higher than the endogenous human ADA gene in the LTC-IC-derived colonies examined. These studies demonstrate that CB progenitor and stem cells can be efficiently infected using retroviral vectors and suggest that CB cells may provide a suitable target population in gene transfer protocols for some genetic diseases. PMID- 8340758 TI - Molecular cloning, expression, and chromosomal localization of the human earliest lymphocyte activation antigen AIM/CD69, a new member of the C-type animal lectin superfamily of signal-transmitting receptors. AB - The activation of T lymphocytes, both in vivo and in vitro, induces the expression of CD69. This molecule, which appears to be the earliest inducible cell surface glycoprotein acquired during lymphoid activation, is involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets. To determine the structural basis for CD69 function, the cDNA coding for CD69 was isolated by a polymerase chain reaction-based strategy using oligonucleotides deduced from peptide sequences of the purified protein. The isolated cDNA exhibited a single open reading frame of 597 bp coding for CD69, and predicted a 199-amino acid protein of type II membrane topology, with extracellular (COOH-terminal), transmembrane, and intracellular domains. The CD69 clone hybridized to a 1.7-kb mRNA species, which was rapidly induced and degraded after lymphocyte stimulation, consistent with the presence of rapid degradation signals at the 3' untranslated region. Transient expression of the polypeptide encoded by CD69 cDNA in COS-7 cells demonstrated that it presented properties comparable to native CD69 protein. The CD69 gene was regionally mapped to chromosome 12 p13-p12 by both somatic cell hybrid DNA analysis and fluorescence in situ hybridization coupled with GTG banding (G bands by trypsin using Giemsa). Protein sequence homology search revealed that CD69 is a new member of the Ca(2+)-dependent (C type) lectin superfamily of type II transmembrane receptors, which includes the human NKG2, the rat NKR-P1, and the mouse NKR-P1 families of NK cell-specific genes. CD69 also has a structural homology with other type II lectin cell surface receptors, such as the T cell antigen Ly49, the low avidity immunoglobulin E receptor (CD23), and the hepatic asialoglycoprotein receptors. The CD69 protein also shares functional characteristics with most members of this superfamily, which act as transmembrane signaling receptors in early phases of cellular activation. PMID- 8340759 TI - P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. AB - Human CD3-16+56+ natural killer (NK) cells have been shown to display a clonally distributed ability to recognize major histocompatibility complex (MHC) class I alleles. Opposite to T lymphocytes, in NK cells, specific recognition of MHC class I molecules appears to induce inhibition of cytolytic activity and, thus, to protect target cells. Since a precise correlation has been established between the expression of the NK-specific GL183 and EB6 surface molecules (belonging to the novel p58 molecular family) and the specificity of NK clones, we analyzed whether p58 molecules could function as receptors for MHC in human NK cells. NK clones displaying the previously defined "specificity 2" and characterized by the GL183+EB6+ phenotype, specifically recognize the Cw3 allele and thus fail to lyse the Fc gamma R+ P815 target cells transfected with Cw3. On the other hand, NK clones displaying "specificity 1" and expressing the GL183-EB6+ phenotype failed to lyse Cw4+ target cells. Addition of the F(ab')2 fragments of either GL183 or EB6 mAb as well as the XA141 mAb of IgM isotype (specific for the EB6 molecules) completely restored the lysis of Cw3-transfected P815 cells by the Cw3-specific NK clones EX2 and EX4. Similarly, both the entire EB6 mAb, its F(ab')2 fragment and the XA141 mAb reconstituted the lysis of C1R, a Fc gamma R- target cell expressing Cw4 as the only serologically detected class I antigen. Thus, it appears that masking of different members of p58 molecules prevents recognition of "protective" MHC class I alleles and thus the delivering of inhibitory signals. Further support to the concept that p58 molecules represent a NK receptor delivering a negative signal was provided by experiments in which the entire anti-p58 mAbs (of IgG isotype) could inhibit the lysis of unprotected Fc gamma R+ P815 target cells, thus mimicking the inhibitory effect of MHC class I molecules. PMID- 8340760 TI - Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses. AB - Dendritic cells are potent antigen-presenting cells for several primary immune responses and therefore provide an opportunity for evaluating the amounts of cell associated antigens that are required for inducing T cell-mediated immunity. Because dendritic cells express very high levels of major histocompatibility complex (MHC) class II products, it has been assumed that high levels of ligands bound to MHC products ("signal one") are needed to stimulate quiescent T cells. Here we describe quantitative aspects underlying the stimulation of human blood T cells by a bacterial superantigen, staphylococcal enterotoxin A (SEA). The advantages of superantigens for quantitative studies of signal one are that these ligands: (a) engage MHC class II and the T cell receptor but do not require processing; (b) are efficiently presented to large numbers of quiescent T cells; and (c) can be pulsed onto dendritic cells before their application to T cells. Thus one can relate amounts of dendritic cell-associated SEA to subsequent lymphocyte stimulation. Using radioiodinated SEA, we noted that dendritic cells can bind 30-200 times more superantigen than B cells and monocytes. Nevertheless, this high SEA binding does not underlie the strong potency of dendritic cells to present antigen to T cells. Dendritic cells can sensitize quiescent T cells, isolated using monoclonals to appropriate CD45R epitopes, after a pulse of SEA that occupies a maximum of 0.1% of surface MHC class II molecules. This corresponds to an average of 2,000 molecules per dendritic cell. At these low doses of bound SEA, monoclonal antibodies to CD3, CD4, and CD28 almost completely block T cell proliferation. In addition to suggesting new roles for MHC class II on dendritic cells, especially the capture and retention of ligands at low external concentrations, the data reveal that primary T cells can generate a response to exceptionally low levels of signal one as long as these are delivered on dendritic cells. PMID- 8340761 TI - Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation. AB - Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320 Lys322 has been identified as a key binding motif for the first component of complement, C1q, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specific residues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in gamma 4 is critical for determining the inability of that isotype to bind C1q and activate complement. Additionally, we provide further evidence that levels of C1q binding do not necessarily correlate with levels of complement activity, and that C1q binding alone is not sufficient for complement activation. PMID- 8340762 TI - Anhydroretinol: a naturally occurring inhibitor of lymphocyte physiology. AB - Vitamin A (retinol) is an essential cofactor for growth of B lymphocytes in culture and for activation of T lymphocytes by antigen receptor-mediated signals. 14-hydroxy-4,14-retro-retinol (14-HRR) a metabolite of retinol, has been implicated as the intracellular mediator of this effect. Anhydroretinol (AR) is a retinol derivative with retro structure produced in activated human B lymphocytes and the insect cell lines SF 21 and Schneider S2. AR reversibly inhibits retinol- and 14-HRR-dependent effects and blocks B lymphocyte proliferation as well as activation of resting T lymphocytes. The intracellular signaling pathway blocked by AR in T cell activation is distinct from the calcineurin/interleukin 2 pathway inhibitable by cyclosporine A or FK-506. PMID- 8340763 TI - Cell surface expression and function of an HLA class II molecule with class I domain configuration. AB - Recombinant major histocompatibility complex (MHC) class II molecules were expressed with extracellular polypeptide domains reorganized to form heavy (H) and light (L) chains (alpha 1-beta 1-beta 2 and alpha 2) analogous to class I. Accurate protein folding and dimerization is demonstrated by the ability of this 3+1-DR1 construct to bind class II-restricted peptides and stimulate CD4+ T cells. Cell surface expression of a functional class II molecule consisting of H and L chains supports the validity of current class II models and affirms the evolutionary relatedness of class I/II. MHC functions that differ between class I/II may be influenced by domain configuration, and the use of domain-shifted constructs will allow examination of this possibility. PMID- 8340764 TI - Protection against antigenically variable Borrelia burgdorferi conferred by recombinant vaccines. AB - Due to local variation in the antigenicity of the agent of Lyme disease (Borrelia burgdorferi), a vaccine derived from any one isolate of this spirochete may fail to protect against the heterogeneous population of organisms that may be present in an enzootic focus. Accordingly, we determined whether antigenically variable spirochetes delivered by naturally infected ticks, collected from a site where transmission is intense, may fail to infect mice actively immunized with recombinant glutathione transferase outer surface fusion proteins A or B (OspA and OspB). Virtually all mice vaccinated by either immunogen appeared not to become infected, as determined by culture or histopathology of their tissues. We conclude that Osp vaccination of mice effectively prevents infection by the agent of Lyme disease in a simulated natural cycle of transmission. PMID- 8340765 TI - Identification of an extracellular plasmin binding protein from nephritogenic streptococci. AB - Examination of the extracellular products of nephritis(+) and nephritis(-) group A streptococci revealed the presence of a 46-kD protein secreted by nephritogenic strains that binds to human plasmin. Immunological data revealed that this protein, called nephritis plasmin binding protein (NPBP), is not related to group A streptokinase nor to a recently described streptococcal dehydrogenase protein. The binding of human plasmin to this protein can be blocked by epsilon-amino caproic acid, indicating the importance of lysine groups in the binding process. Mutanolysin extracts of cell walls from these nephritogenic strains probed with anti-NPBP antibody were negative for cell wall-bound NPBP. Serological data with acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever sera indicated that the protein reacts preferentially with APSGN sera. Amino acid sequence analysis and immunological reactivity suggest NPBP is the streptococcal pyrogenic exotoxin B precursor, also previously described as zymogen (streptococcal proteinase precursor). The secretion of both group A streptokinase and a secreted plasmin binding protein in the same nephritogenic strain raises an intriguing hypothesis of the mechanisms of action of this protein in APSGN. PMID- 8340766 TI - Spatial guidance of choice behavior in the radial-arm maze. AB - In 6 experiments, the performance of male rats in a 12-arm radial maze was examined. The focus of study was the extent to which the spatial location of individual baited maze arms was determined before the rat was exposed to the extramaze visual cues corresponding to the arm, and thereby guided the rat toward the location of baited arms. Such spatial guidance of choice behavior implies a spatially organized cognitive representation of maze arms (i.e., a cognitive map). A higher level of spatial guidance was found when visual access to extramaze cues was restricted than when it was unrestricted. There was no evidence of a difference between the level of spatial guidance in the context of working memory performance and reference memory performance. Some evidence that intramaze cues contributed to microchoice guidance was found. However, spatial guidance, under at least some conditions, is best explained in terms of cognitive mapping. PMID- 8340767 TI - Local time horizons in Pavlovian learning. AB - Responding to a conditioned stimulus (CS) is impaired if the CS is trained in the presence of excitatory local context cues. Four lick suppression experiments with rats explored whether this local context effect arises from the influence of excitatory cues that precede or that follow a reinforced target CS. Pretrained nontarget stimuli served as local context cues that occurred (a) immediately before and after the target CS trial, (b) immediately before or after the target CS trial, or (c) only before or after the target CS trial with varying intervals between the nontarget stimulus and target CS. Results indicated similar control over responding to the target CS by the preceding and following nontarget cues. This outcome implies a symmetrical window of memory integration (local time horizon) for a Pavlovian CS. Possible mechanisms underlying the detrimental effect of embedding a CS in an excitatory local context are discussed. PMID- 8340768 TI - Extending continuous versus discontinuous conditioned stimuli before versus after unconditioned stimuli. AB - Conditioned suppression was used with rats to study the effects of extending conditioned stimuli (CSs) before versus after the delivery of unconditioned stimuli. These extensions are termed B and A extensions, respectively. Within group designs were used to compare the effects of extending CSs when 2-min parts of those CSs were separated by temporal gaps of 6 min versus a separation of no gap. The results were as follows: (a) B extensions weakened conditioning more than did A extensions, with or without gaps; (b) under some conditions, this asymmetrical effect persisted with extended training; (c) gaps between 2-min parts of a B extension had no detectable effect; and (d) under some parameter values, gaps between 2-min parts of an A extension weakened conditioning significantly. These results are better predicted by the Sometimes Opponent Process model (SOP; A. R. Wagner, 1981) than by the Rescorla-Wagner-Frey-Sears real-time model (J. J. B. Ayres, M. Albert, & J. C. Bombace, 1987). PMID- 8340769 TI - Real-time processing of serial stimuli in classical conditioning of the rabbit's nictitating membrane response. AB - Real-time models contend that a conditioned stimulus (CS) gives rise to a cascade of hypothetical stimuli that govern conditioned responses (CRs) on a moment-by moment basis. Experiments with the rabbit nictitating membrane response successfully extended these models to external stimuli. CSs were trained in sequence with an unconditioned stimulus (CSA-CSB-US). When the CSA-CSB interval was shortened, the CR was compressed; when the CSA-CSB interval was lengthened, the CR was broadened. Peaks appeared at 2 places, namely, 1 following CSA by a period equal to its CS-US interval and another following CSB by its CS-US interval. Outside the sequence, the individual CSs evoked CRs located between their respective CS-US intervals. When, however, the 2 CSs were trained separately, the CRs were appropriate to their respective CS-US intervals when tested alone or in sequence. The results are discussed in terms of the J.E. Desmond and J.W. Moore (1988) and S. Grossberg and N.A. Schmajuk (1989) models. PMID- 8340770 TI - Single-incentive selective associations produced solely as a function of compound stimulus conditioning context. AB - Barpressing was maintained in a tone-plus-light (TL) condition in 2 groups of rats by shock-related contingencies and in 2 other groups by food-related contingencies. Responding ceased in TL absence (TL). Contingency arrangements made TL hedonically positive, relative to TL, for 1 shock group and for 1 food group and hedonically negative for 1 shock group and for 1 food group. In a stimulus-element test, the visual modality was dominant when TL was hedonically positive, whereas auditory control increased when TL was negative, irrespective of the reinforcers involved. Within-incentive contingency manipulations produced selective associations hitherto ascribed to stimulus-reinforcer interactions, suggesting that biological constraints on learning may operate at the level of conditioned psychological states. PMID- 8340771 TI - Cost-effectiveness of alcohol and drug treatment programs. PMID- 8340772 TI - The health-care revolution begins at home. PMID- 8340773 TI - While we're at it.... PMID- 8340774 TI - Kyrle's disease. Effectively treated with isotretinoin. AB - Kyrle's disease is an uncommon dermatologic entity with characteristic clinical and histopathologic features. A case is recorded in a 63-year-old man undergoing hemodialysis for chronic renal failure. Systemic isotretinoin treatment for 13 weeks resulted in a complete clearance of the cutaneous lesions. Systemic treatment is effective and could be considered preferred therapy. PMID- 8340775 TI - Clinical privileges for laparoscopic surgery. AB - Laparoscopic cholecystectomy has undergone an explosive growth. Its benefits to patients--shortened recovery time and less pain--became immediately obvious. The procedure's development and adaptation have largely been devised and implemented by ingenious and creative private practitioners, not the typical mode of introduction. Most or many new procedures in the past evolved from academic institutions after laboratory and then clinical trials. With rapid development and acceptance has come an additional new burden among medical practitioners: credentialing and granting clinical privileges. PMID- 8340776 TI - Benlate. A medical and scientific controversy. AB - Benlate, a fungicide, has been used for over 20 years in Florida to treat agricultural crops and ornamentals. In the past few years, there have been reports of crop damage and health effects from exposure. Physicians should be aware of research findings regarding these effects. PMID- 8340777 TI - The future ain't what it used to be. PMID- 8340778 TI - Stress and infections. AB - Neurotransmitters and neuroendocrine hormones can modify the functioning of immune cells and conversely cytokines produced by immune cells can alter brain homeostasis. This connection is further manifested by experimental studies showing a relationship between stress and resistance to infection. Human subjects with a high stress index were shown to be more susceptible to infection with common cold viruses. Furthermore, a diversity of experimental animal paradigms show that laboratory stressors such as forced exercise, avoidance learning, restraint, isolation, and cold exposure make animals more susceptible to primary infection with a variety of viruses and bacteria. The cellular and molecular basis for the observed modulation of host resistance is not fully understood but involves altered functioning of both T lymphocytes and cells of the hypothalamic pituitary adrenal axis. Also involved is the altered production of cytokines and hormones produced by the immune system and brain. PMID- 8340779 TI - Applying for medical staff membership. Peer review. Part I. PMID- 8340780 TI - And justice for all. PMID- 8340781 TI - In remembrance Anton Mark Krone, M.D. PMID- 8340782 TI - Access, cost and quality. PMID- 8340783 TI - The activity-stress paradigm: possible mechanisms and applications. AB - The mechanisms and applications of the activity-stress (A-S) research paradigm are examined in this article. Past research has reflected the value of this paradigm in the investigation of ulcerogenesis. Evidence is offered to support a theory explaining the excessive running observed in the A-S animals, according to which, animals commence running to increase body temperature after failing to adapt to the restricted feeding regime. Further, excessive running levels are hypothesized to be sustained by reinforcement resulting from increased mesolimbic dopaminergic activity. Finally, parallels between the behavior observed in the A S animals and some forms of maladaptive behavior observed in humans are discussed. PMID- 8340784 TI - Psychological studies in nonionizing electromagnetic energy research. AB - Research on nonionizing electromagnetic (NIEM) energy has focused on potential hazards, and to a lesser degree beneficial applications, of radiofrequency (RF) fields and extremely low frequency (ELF) fields. The history of research on the potential biological effects of NIEM contains many psychological investigations. These psychological investigations were conducted primarily in the discipline of biopsychology and included interdisciplinary cooperation with engineering, physical sciences, and other disciplines not routinely associated with psychology. The current recommended exposure level for RF is based on behavioral observations of laboratory animals. Psychology has been and continues to be in the midst of controversy regarding the ability of low-frequency, low-level electromagnetic energy or electric and magnetic fields to affect living organisms. PMID- 8340785 TI - The effects of chronic prenatal exposure to nicotine on the behavior of guinea pigs (Cavia porcellus). AB - Three groups of 15 offspring from guinea pig dams were injected twice daily throughout gestation with one of three doses (0.5, 1.5 or 2.5 mg/kg) of nicotine hydrogen tartrate. These offspring and 15 saline-exposed offspring were tested on several behavioral measures. Offspring of nicotine-treated dams had significantly lower rates of spontaneous alternation as neonates. The 1.5 and 2.5 mg/kg nicotine-exposed offspring also alternated less at puberty than control offspring and would not enter an unfamiliar stimulus alley that a majority of controls entered. Nicotine offspring, as adults, performed significantly poorer than their controls on errors and trials to criterion on a discrimination and reversal task. Prenatal nicotine treatment resulted in performance deficits on both learned and innate behavioral measures throughout development and adulthood. PMID- 8340786 TI - Keeping an eye on the brain: the role of visual experience in monkeys and children. AB - The quality of visual experience during infancy determines the functional sensitivity and precision of the mature primate visual system. Infant monkeys subjected to monocular form deprivation show a period of critical visual development that, though decreasing in sensitivity, lasts throughout the first 2 years of life. Photopic threshold spectral sensitivity appears to have a briefer critical period, which is essentially complete by 6 months old, whereas scotopic visual functions appear well developed by 3 months old. Binocular visual functions seem to have the longest period of sensitivity to abnormal visual experience because periods of monocular form deprivation initiated during the first 2 years affect visual functions. Viewing the world through prisms, which mimics the condition of strabismus, causes a permanent loss of cortical binocular cells and stereopsis in monkeys. This result explains stereoblindness in children having equivalent clinical histories. PMID- 8340787 TI - A note on the early history of electrical stimulation of the human brain. AB - We address inconsistencies in two areas concerning who was first to electrically stimulate a human's brain. First, Boring (1950) and others attributed priority to Eduard Hitzig based on information mentioned somewhat incidentally in Fritsch and Hitzig's (1870) classic work using dogs. Others cited Fritsch and Hitzig but attributed priority to Roberts Bartholow (1874). Second, our examination of translations of Fritsch and Hitzig, especially of footnote 16 in Hitzig's report (1870) of a human case, revealed errors, omissions, and inconsistencies. To aid our inquiry, we requested and received new translations of footnote 16 and of Hitzig's report. PMID- 8340788 TI - Multiple sclerosis: does epidemiology contribute to providing etiological clues? AB - The epidemiological approach has undoubtedly contributed to our knowledge of Multiple Sclerosis (MS) by providing some etiological hypotheses in spite of the fact that a definitive basis for the conclusive resolution of its enigma is still lacking. Epidemiological studies have indicated that MS has an uneven geographical distribution and a changing incidence over time at least in several areas of the world: this suggests an etiological role of both genetic and environmental factors. The racial difference in disease risk, the results of familial and twin studies as well as the association between MS and some HLA markers, support the great importance of genetic factors. On the other hand, the evidence of temporal trends and the data from migrant studies seem to underline the etiological contribution of environmental factors. In the light of these results much of the present views have emerged interpreting the disease as caused by multiple factors acting at a susceptible age in genetically predisposed subjects. PMID- 8340789 TI - Generation of effector cytotoxic T cells from cytotoxic T cell precursors: role of soluble factors. AB - Cytotoxic T lymphocytes (CTL) have long been recognized as playing a major role in the immune response to alloantigens and viral antigens as well as tumor antigens. The progress of the last decade in the identification and characterization of soluble factors involved in the regulation of the immune response has greatly improved our knowledge of the mechanisms of CTL activation and regulation. This review will summarize the data available in the literature regarding different lymphokines and their specific activity on CTL. In addition it will point out a few of the elements of the systems that hamper its full understanding and it will suggest possible directions for future research. PMID- 8340790 TI - Multiple sclerosis: from immunogenetics to immunotherapy. PMID- 8340791 TI - Memory and "frontal lobe" dysfunction in multiple sclerosis. AB - The characteristics of memory disturbance in multiple sclerosis (MS) are briefly reviewed and the interactions of conceptual and memory dysfunction in MS are considered. Although conceptual functions such as abstraction and problem solving traditionally have been considered to be frontal lobe functions, there is now convincing evidence from studies of patients with focal brain lesions that these capacities are not localized to the frontal lobes. Thus, the concept of frontal lobe dysfunction in MS is without empirical support. Nevertheless, studies examining the relationship between memory and conceptual impairment in MS have value for both basic and clinical neuroscience. PMID- 8340792 TI - Frontal lobe dysfunction in multiple sclerosis as assessed by means of Lurian tasks: effect of age at onset. AB - We investigated frontal cognitive function in a group of 153 patients with multiple sclerosis and 100 healthy controls using a global scale composed by a set of items from the Luria-Nebraska Neuropsychological Battery (LNNB) which has been validated by Malloy and colleagues on frontally damaged patients. A second scale was built with LNNB items tapping parietal lobes function. Patients who were specifically impaired on the frontal scale (12%) had a shorter disease duration and were less physically disabled than those failing on the parietal tasks (8.5%) or those showing combined deficits (21.5%). Sixty-four patients were also tested on the Wisconsin Card Sorting Test (WCST). Twenty-seven (37.5%) patients were found to be impaired on the WCST, but the latter could not predict reliably their performance on the LNNB frontal scale. We also examined whether age of onset and disease duration could have had any effect on the cognitive performance of selected groups of patients. We found that relative to normals, deficits on the frontal scale were more severe in patients with a clinical onset around age 20 than in patients with a later onset (i.e., around 35), the two groups being comparable for duration and degree of disability. Furthermore, patients with a longstanding illness (> 10 years) were more affected on visuospatial processing and frontal control of language than those with a short duration (1.5 yrs). We propose that a greater disease activity interacting with contingent (developmental?) factors is responsible for the appearance of transient frontal deficits in several young MS patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340793 TI - Neuropsychology and multiple sclerosis: diagnostic and rehabilitative approaches. AB - The frequency of cognitive deficits in multiple sclerosis (MS) patients is rather high and the estimates vary between 43% and 72% depending on the patient samples studied as well as on the methods of cognitive assessment. Despite the great impact of cognitive dysfunction on several aspects of the quality of life, the importance of accurate assessment and rehabilitation of neuropsychological deficits in MS patients has long been ignored. In this article, we first describe tests for the assessment of impairments, disabilities and handicaps. We emphasize that after screening with brief assessment instruments, detailed testing of the basic target deficits is mandatory for the planning of special cognitive training programs. Second, the correlation of certain cognitive deficit patterns with important magnetic resonance imaging (MRI) variables such as total lesion area, size of the corpus callosum and specific lesion location is outlined in detail. Third, some recommendations are made with regard to general rehabilitation principles such as restitution, compensation and adaptation as well as for special rehabilitation techniques including cognitive retraining of basic deficits and/or training of activities of daily living. Finally, we emphasize that there is a need for the development of tailor-made neuropsychological rehabilitation techniques for MS patients, which take into account the course and stage of the disease as well as the specific psychosocial problems of the individual patient. PMID- 8340794 TI - Anatomical and functional correlates of cognitive deficit in multiple sclerosis. AB - This brief article reviews the present state of knowledge concerning the relationship between structural and functional cerebral abnormalities and the cognitive deficits associated with multiple sclerosis. Currently available neuroimaging techniques have substantially contributed to a better understanding of the latter, suggesting that cortical-subcortical disconnection is the most likely cause of the cognitive disturbance. Longitudinal studies are needed to determine the natural history of the cognitive deficit and its relationship to the cerebral changes detected by neuroimaging techniques. PMID- 8340795 TI - MRI and cognitive patterns in relapsing-remitting multiple sclerosis. AB - We studied the relationships between magnetic resonance imaging (MRI) and the Luria-Nebraska Neuropsychological Battery (LNNB) in 64 patients with relapsing remitting multiple sclerosis (MS). MRI films were scored according to arbitrary descriptive criteria designed to emphasize patterns of alterations. Five groups were created: group 1 and 2 had typical discrete white matter lesions, group 3 had confluent lesions, group 4 had large discrete lesions and group 5 had only few small lesions. In addition, groups 2 and 3 had evidence of parenchymal atrophy. Groups 2 and 3 were the most impaired on the LNNB, but none of these patients was actually demented. Groups 1 and 5 were globally intact in spite of very different mean age and MRI pattern. Group 4 was composed of younger subjects with a shorter disease duration; they showed mild loss of attentive and abstracting abilities. We suggest that since their MRI was showing greater signs of local biological activity their mental deficits may be a transitory condition capable of two distinct outcomes: a favorable one as in groups 1 and 5, and a slowly progressive one associated with loss of brain tissue as in groups 2 and 3. PMID- 8340796 TI - Brain magnetic resonance imaging correlates of cognitive impairment in multiple sclerosis. AB - We evaluated the correlations between cognitive impairment, clinical and brain magnetic resonance imaging (MRI) findings in 100 patients with multiple sclerosis (MS). The performance on one or more neuropsychological tests was abnormal in 47% of the 64 patients who completed the entire neuropsychological battery; the cognitive impairment was mild in 14 (22%) and severe in 16 (25%). Performance on any single neuropsychological test was unrelated to clinical parameters (age, duration of the disease, disability). The neuropsychological performance of relapsing-remitting patients was better than in patients with a chronic progressive disease. The mean scores for almost all the neuropsychological tests were significantly lower in patients with severe ventricular dilatation and corpus callosum atrophy than in patients in whom these structures were little affected. Mean scores for WMS, performance Intelligence Quotient (IQ), total IQ and Token Test (TT) were also significantly correlated with the widening of cortical sulci and total lesional scores. Our data support the contention that the involvement of pathways that are critical for a given cognitive process as well as the progression of the axonal degeneration and sclerosis seem to play important roles in the pathophysiology of cognitive dysfunction in MS. PMID- 8340797 TI - Health Status of American Men--a study of post-vasectomy sequelae. PMID- 8340798 TI - Community services in the 1990s: are they meeting the needs of caregivers? AB - The community-based, long-term care system not only sustains the older person in the community but also helps to maintain him or her at the highest level of functioning possible. A broad spectrum of services exists, including personal care, transportation, home-delivered meals, adult day care, and respite care. One hundred sixty-eight primary caregivers were were interviewed regarding awareness of, inquiry into, utilization of, and satisfaction with community services during the caregiving period. The majority of caregivers were aware of and utilized 7 of the 15 services listed, including personal care services, home-delivered meals, rehabilitation services, housekeeping services, nursing services, and information referral services. Nurses remain the key individuals in providing linkages among elderly and their families and community-based services. One of the key roles that nurses can play is to inform caregivers about available community services, to help caregivers recognize the need for these services, to assist them in accessing these services, and to recognize their need for support during this process. Finally, the community nurse can also provide support to the caregiver when institutionalization of the older family member becomes a reality. PMID- 8340800 TI - Client satisfaction with home health care nursing. AB - Client satisfaction can serve as an outcome indicator of the quality of nursing care received, yet there is a paucity of literature and research describing client satisfaction within the home health care arena. This descriptive study explores the domain of client satisfaction with home health nursing as assessed by the Client Satisfaction Survey (CSS) developed by Reeder and Chen (1990). The overall mean response for surveyed clients is 1.6966, indicating satisfaction with the nursing services received. Through factor analysis, four factors were identified as dimensions of client satisfaction: (a) Technical Quality of Care, (b) Communication, (c) Personal Relationships Between Client and Provider, and (d) Delivery of Services. This study validates that consumer clients can willingly participate in the objective evaluation of the nursing care they receive. In addition, the measurement of satisfaction using instruments with established reliability and validity can contribute to the advancement of the definition of client satisfaction of the home care client. PMID- 8340799 TI - An assessment of diabetes self-care barriers in older adults. PMID- 8340801 TI - Developing and implementing a community intergenerational program. AB - Although intergenerational programs are becoming increasingly popular, there has been little documentation linking independent yet isolated seniors with children. This article discusses the development and implementation of a community intergenerational program. Elementary school students interacted with seniors at a nearby senior citizen apartment complex during eight 2-hr after-school meetings. Various recruitment strategies were needed to reach this vulnerable senior population, and activities had to be carefully monitored to promote intergenerational exchange. Evaluation of the program showed both the value of such interaction to the students and seniors and the importance of the nurse's role in ensuring that the program's benefits were realized. PMID- 8340802 TI - Training imperatives for volunteers caring for high-risk, vulnerable populations. AB - Today, vulnerable populations expand as the threats of homelessness and communicable diseases continue to grow. Volunteers are moved to serve in areas in which they may not be well prepared. We identify the caring needs of high-risk, vulnerable populations and the needs of volunteers; we also conceptualize, develop, implement, and evaluate a training program for volunteers who serve homeless persons and families. This training program and the imperatives that undergird it are presented as a model applicable to the training of volunteers serving high-risk, vulnerable populations. PMID- 8340803 TI - Glenridge: a partnership for eldercare. AB - Societal trends of rising health care costs and changing elder demographics dictate the need for new and innovative approaches to cost-effective health care and other services for this age group. As individuals age, their need for assistive services increases, and access becomes a priority. Housing models that provide an environment which facilitates independent living are very desirable and usually cost-containing by postponing and/or preventing institutionalization. Through access to health promotion and maintenance services, residents are enabled to stay in their preferred home environments as long as possible (Zink & Bissonnette, 1990, p. 70). A major obstacle to these models is a clear definition of the elder population's needs and a coordinated effort to meet these needs (Little, 1980). An innovative partnership involving nursing education, an area agency on aging, and a developer provided a unique opportunity for a school of nursing to play a pivotal role in the coordination of health care for "well" older adults. PMID- 8340804 TI - The retinal fate of Xenopus cleavage stage progenitors is dependent upon blastomere position and competence: studies of normal and regulated clones. AB - The clonal origin of the stage 43-44 Xenopus retina from cleavage stage precursors was quantitatively assessed with lineage tracing techniques. The retina descends from a specific subset of those blastomeres that form forebrain. The most animal dorsal midline cell (D1.1.1) produced about half of the retina, the three other dorsal ipsilateral blastomeres each produce about an eighth of the retina, and the four contralateral dorsal blastomeres and an ipsilateral ventral-animal cell together produce the remaining eighth of the retina. There was no significant spatial segregation of the clones derived from different progenitors in either the anterior-posterior or dorsal-ventral axes of the retina and no boundaries between clones were observed. Instead, the clones intermixed to form multiple radial subclones that were equivalent to those demonstrated by marking optic vesicle progenitor cells (Holt et al., 1988; Wetts and Fraser, 1988). This mosaic pattern was initiated by the beginning of gastrulation, advanced in the neural plate, and virtually complete in the optic vesicle. At optic vesicle stages cell movement within subclones was restricted, resulting in the formation of lineally related columns of cells in the mature retina. To determine if the blastomere progenitors are determined to produce these retinal lineage patterns, the major retinal progenitor (D1.1.1) was deleted bilaterally. About 60% of the tadpoles developed normal-appearing eyes; of these the retinas in two-thirds were normal in size and the rest were smaller. The blastomeres surrounding the deleted D1.1.1 progenitors changed their contributions to retina in different ways to effect a complete or partial restoration. Ventral blastomeres, which normally contribute mainly to the tail, produced substantial amounts of the retina while dorsal blastomeres, which normally contribute mainly to the head, decreased their contribution to the retina. To determine whether these changes in retinal lineage were due to changes in blastomere position after the surgery, various other blastomeres were deleted prior to lineage mapping. Dorsal-animal blastomeres took over the retinal fate of their dorsal-vegetal neighbors after those neighbors were deleted, but did not change fate after the deletion of their ventral-animal neighbors. This result suggests that dorsal animal blastomeres change positional values in only one direction (dorsal to vegetal) after neighbor cell deletion, and that retinal fate is dictated by blastomere position. To test this hypothesis directly, different ventral and vegetal blastomeres, which normally do not produce retina, were transplanted to the position of D1.1.1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8340805 TI - Targeted ablation of diverse cell classes in the nervous system in vivo. AB - The study of both the function and development of complex neural systems would be greatly facilitated by a means for systematically blocking intercell communication. One way of preventing cells from signaling each other is to remove them from the system by ablation. Here we present a general technique for visualizing and ablating selected cell classes in vivo. The cells of interest are genetically engineered so that they can be selectively labeled with a photoactivatable dye and visualized in living preparations; the dye-labeled cells can then be photoablated. This approach is applicable to a broad range of cell types, in organisms amenable to gene transfer, and permits ablations to be performed at different developmental stages or in the adult. We demonstrate the use of this technique on several cell types in the mouse retina and cerebral cortex, and in the zebrafish embryo. PMID- 8340806 TI - A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. AB - We describe a novel slow oscillation in intracellular recordings from cortical association areas 5 and 7, motor areas 4 and 6, and visual areas 17 and 18 of cats under various anesthetics. The recorded neurons (n = 254) were antidromically and orthodromically identified as corticothalamic or callosal elements receiving projections from appropriate thalamic nuclei as well as from homotopic foci in the contralateral cortex. Two major types of cells were recorded: regular-spiking (mainly slow-adapting, but also fast-adapting) neurons and intrinsically bursting cells. A group of slowly oscillating neurons (n = 21) were intracellularly stained and found to be pyramidal-shaped cells in layers III VI, with luxuriant basal dendritic arbors. The slow rhythm appeared in 88% of recorded neurons. It consisted of slow depolarizing envelopes (lasting for 0.8 1.5 sec) with superimposed full action potentials or presumed dendritic spikes, followed by long-lasting hyperpolarizations. Such sequences recurred rhythmically at less than 1 Hz, with a prevailing oscillation between 0.3 and 0.4 Hz in 67% of urethane-anesthetized animals. While in most neurons (approximately 70%) the repetitive spikes superimposed on the slow depolarization were completely blocked by slight DC hyperpolarization, 30% of cells were found to display relatively small (3-12 mV), rapid, all-or-none potentials after obliteration of full action potentials. These fast spikes were suppressed in an all-or-none fashion at Vm more negative than -90 mV. The depolarizing envelope of the slow rhythm was reduced or suppressed at a Vm of -90 to -100 mV and its duration was greatly reduced by administration of the NMDA blocker ketamine. In keeping with this action, most (56%) neurons recorded in animals under ketamine and nitrous oxide or ketamine and xylazine anesthesia displayed the slow oscillation at higher frequencies (0.6-1 Hz) than under urethane anesthesia (0.3-0.4 Hz). In 18% of the oscillating cells, the slow rhythm mainly consisted of repetitive (15-30 Hz), relatively short-lasting (15-25 msec) IPSPs that could be revealed by bringing the Vm at more positive values than -70 mV. The long-lasting (approximately 1 sec) hyperpolarizing phase of the slow oscillation was best observed at the resting Vm and was reduced at about -100 mV. Simultaneous recording of another cell across the membrane demonstrated synchronous inhibitory periods in both neurons. Intracellular diffusion of Cl- or Cs+ reduced the amplitude and/or duration of cyclic long-lasting hyperpolaryzations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8340807 TI - Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. AB - The newly described slow cortical rhythm (approximately 0.3 Hz), whose depolarizing-hyperpolarizing components are analyzed in the preceding article, is now investigated from the standpoint of its relations with delta (1-4 Hz) and spindle (7-14 Hz) rhythmicity. Regular-spiking and intrinsically bursting cortical neurons were mostly recorded from association suprasylvian areas 5 and 7; fewer neurons were also recorded from pericruciate motor and posterolateral visual areas. Although most cells were investigated under various anesthetics, a similar slow cortical rhythm was found in animals with brainstem transection at the low- or high-collicular levels. These cerveau isole (isolated forebrain) preparations display the major sleep rhythms of the EEG in the absence of general anesthetics. In 38% of recorded cortical neurons (n = 105), the slow rhythm was combined with delta oscillation. Both cellular rhythms were phase locked to the slow and delta oscillations in the surface- and depth-recorded EEG. In a group of this cell sample (n = 47), delta activity occurred as stereotyped, clock-like action potentials during the interdepolarization lulls of the slow rhythm. In another neuronal subsample (n = 58), delta events were grouped in sequences superimposed upon the depolarizing envelope of the slow rhythm, with such sequences recurring rhythmically at approximately 0.3-0.4 Hz. The associations between the two cellular and EEG rhythms (1-4 Hz and 0.3-0.4 Hz) were quantified by means of autocorrelograms, cross-correlograms, and spike-triggered averages. In 26% of recorded neurons (n = 72), the slow rhythm was combined with spindle oscillations. Regular-spiking cortical neurons fully reflected the whole frequency range of thalamically generated spindles (7-14 Hz). However, during similar patterns of EEG spindling, intrinsically bursting cells fired grouped action potentials (with intraburst frequencies of 100-200 Hz) at only 2-4 Hz. The dependence of the slow cortical oscillation upon the thalamus was studied by lesions and stimulation. The slow rhythm survived extensive ipsilateral thalamic destruction by means of electrolytic lesions or kainate-induced loss of perikarya in thalamic nuclei that were input sources to the recorded cortical neurons. To further prevent the possibility of a thalamic role in the genesis of the slow rhythm, through the contralateral thalamocortical systems and callosal projections, we also transected the corpus callosum in thalamically lesioned animals, and still recorded the slow rhythm in cortical neurons. These data indicate that the thalamus is not essentially implicated in the genesis of the slow rhythm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8340808 TI - The slow (< 1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks. AB - As most afferent axons to the thalamus originate in the cerebral cortex, we assumed that the slow (< 1 Hz) cortical oscillation described in the two companion articles is reflected in reticular (RE) thalamic and thalamocortical cells. We hypothesized that the cortically generated slow rhythm would appear in the thalamus in conjunction with delta and spindle oscillations arising from intrinsic and network properties of thalamic neurons. Intracellular recordings have been obtained in anesthetized cats from RE (n = 51) and cortically projecting (n = 240) thalamic neurons. RE cells were physiologically identified by cortically evoked high-frequency spike bursts and depolarizing spindle oscillations. Thalamocortical cells were recognized by backfiring from appropriate neocortical areas, spindle-related cyclic IPSPs, and hyperpolarization-activated delta oscillation consisting of rhythmic low threshold spikes (LTSs) alternating with afterhyperpolarizing potentials (AHPs). The slow rhythm (0.3-0.5 Hz) was recorded in 65% of RE neurons. In approximately 90% of oscillating cells, the rhythm consisted of prolonged depolarizations giving rise to trains of single action potentials. DC hyperpolarization increased the synaptic noise and, in a few cells, suppressed the long-lasting depolarizing phase of the slow rhythm, without blocking the fast EPSPs. In approximately 10% of oscillating neurons, the hyperpolarizing phase of the oscillation was much more pronounced, thus suggesting that the slow rhythm was produced by inhibitory sculpturing of the background firing. The slow oscillation was associated with faster rhythms (4-8 Hz) in the same RE neuron. The slow rhythm of RE neurons was closely related to EEG wave complexes recurring with the same frequency, and its strong dependency upon a synchronized state of cortical EEG was observed during shifts in EEG patterns at different levels of anesthesia. In 44% of thalamocortical cells the slow rhythm of depolarizing sequences was apparent and it could coexist with delta or spindle oscillations in the same neuron. The occurrence of the slowly recurring depolarizing envelopes was delayed by the hyperpolarizing spindle sequences or by the LTS-AHP sequences of delta oscillation. The hyperpolarization-activated delta potentials that tended to dampen after a few cycles were grouped in sequences recurring with the slow rhythm. We finally propose a unified scenario of the genesis of the three major sleep rhythms: slow, delta, and spindle oscillations. PMID- 8340809 TI - Development of segment specificity in identified lineages of the grasshopper CNS. AB - The purpose of this study was to determine the factors underlying differences in population size and composition between segmentally homologous neuronal lineages. The segmental median neuroblasts (MNBs) of grasshoppers are identified stem cells that each produce a midline group of neurons. We traced the embryonic development of the group in two disparate segments, counting MNB progeny and profiles of dying cells in fixed and stained preparations of staged embryos. In the metathoracic segment (T3), about 95 MNB progeny survive embryonic development, whereas in the next posterior segment, the first abdominal (A1), only about 60 survive. In T3, the MNB arises at 29% of embryogenesis and dies at 78%, whereas in A1 the MNB arises at 30% and dies at 73%. In T3, the number of MNB progeny initially increases at a steady rate, 10 cells being added per 5% of embryogenesis. Between 70% and 78% growth tapers off; although the T3 MNB continues to divide, cells die at the same time, specifically removing last-born progeny. By contrast, in A1 the MNB progeny increase in two phases, one from 30% to 45% and the other from 60% to 73%, again at the rate of 10 cells per 5%. Between the two phases, the number of A1 progeny is stable. The A1 MNB continues to divide, but cells die at the same time, specifically removing earlier-born progeny. The episodes of cell death in A1 and T3 coincide with embryonic molts, and thus may be hormonally triggered. Cell death is greater in A1 than T3, accounting for most of the difference in population size. The difference in MNB longevity makes a lesser contribution. The present data, together with corollary anatomical data (Thompson and Siegler, 1991), support the hypothesis that progeny fated to become certain neuronal types are selectively removed from the two MNB lineages: intersegmental interneurons from T3 and efferent neurons and local interneurons from A1. PMID- 8340810 TI - Specific induction of intracellular calcium oscillations by complement membrane attack on oligodendroglia. AB - Oligodendroglia (ODG) are unique among glial cell types in their capacity to activate complement in the absence of antibody, causing insertion of the potentially damaging membrane attack complex (MAC) into the plasma membrane. Using microfluorimetry of indo-1 fluorescence we have detected a complex oscillatory [Ca2+]i response in ODG following exposure to sublethal dilutions of serum-derived complement. Oscillations were transitory and preceded complete and stable return to resting [Ca2+]i levels, whereas nonoscillating ODG underwent rapid lysis. Depletion of the terminal complement component C9 from serum removed the oscillatory stimulus, which could be restored by reconstitution with purified C9. Exposure to the C9-homologous peptide melittin produced [Ca2+]i oscillations similar in pattern to those induced by whole serum. However, this type of response could not be reproduced by Ca2+ ionophores or mechanical wounding, suggesting that oscillations cannot be provoked by Ca2+ influx alone and depend on the presence of the MAC or a pore-forming lesion. Oscillations were not prevented in the continuous presence of caffeine, demonstrating independence from caffeine-releasable intracellular stores. Inhibition of the endoplasmic reticular Ca(2+)-ATPase with thapsigargin produced an abrupt elevation in [Ca2+]i but did not alter the latency between exposure to serum and the initial complement induced transient. However, the slope of this initial transient was considerably reduced and oscillations suppressed, demonstrating dependence of the oscillatory mechanism on functional endoplasmic reticular Ca2+ stores. The coincidence of ODG recovery with oscillating [Ca2+]i suggests that the complex calcium signal that follows MAC attack may stimulate repair or protective mechanisms. PMID- 8340811 TI - Inward-rectifying potassium channels in retinal glial (Muller) cells. AB - The voltage- and K(+)-dependent properties of Muller cell currents and channels were characterized in freshly dissociated salamander Muller cells. In whole-cell voltage-clamp experiments, cells with endfeet intact and cells missing endfeet both displayed strong inward rectification. The rectification was similar in shape in both groups of cells but currents were 9.2 times larger in cells with endfeet. Ba2+ at 100 microM reduced the inward current to 6.8% of control amplitude. Decreasing external K+ concentration shifted the cell current-voltage (I-V) relation in a hyperpolarizing direction and reduced current magnitude. In multichannel, cell-attached patch-clamp experiments, patches from both endfoot and soma membrane displayed strong inward rectification. Currents were 38 times larger in endfoot patches. In single-channel, cell-attached patch-clamp experiments, inward-rectifying K+ channels were, in almost all cases, the only channels present in patches of endfoot, proximal process, and soma membrane. Channel conductance was 27.8 pS in 98 mM external K+. Reducing external K+ shifted the channel reversal potential in a hyperpolarizing direction and reduced channel conductance. Channel open probability varied as a function of voltage, being reduced at more negative potentials. Together, these observations demonstrate that the principal ion channel in all Muller cell regions is an inward-rectifying K+ channel. Channel density is far higher on the cell endfoot than in other cell regions. Whole-cell I-V plots of cells bathed in 12, 7, 4, and 2.5 mM K+ were fit by an equation including Boltzmann relation terms representing channel rectification and channel open probability. This equation was incorporated into a model of K+ dynamics in the retina to evaluate the significance of inward-rectifying channels to the spatial buffering/K+ siphoning mechanism of K+ regulation. Compared with ohmic channels, inward-rectifying channels increased the rate of K+ clearance from the retina by 23% for a 1 mM K+ increase and by 137% for a 9.5 mM K+ increase, demonstrating that Muller cell inward-rectifying channels enhance K+ regulation in the retina. PMID- 8340812 TI - The myomodulin-related neuropeptides: characterization of a gene encoding a family of peptide cotransmitters in Aplysia. AB - The myomodulin-related peptides comprise a family of cotransmitters that modulate neuromuscular signaling in the feeding system of Aplysia. In this study, cDNA clones encoding a myomodulin precursor polypeptide were isolated and characterized. This precursor contains seven different myomodulin-related peptides, one of which, myomodulin A, is present in 10 contiguous copies. The sequence of a myomodulin genomic clone indicates that all of these myomodulin related peptides are encoded on a single exon. The myomodulin gene is expressed in a tissue-specific manner and myomodulin mRNA is localized to specific neurons in the Aplysia CNS. The presence of multiple related neuropeptides can greatly increase the range and precision of signaling at synapses where they act as modulator cotransmitters. PMID- 8340813 TI - Modulation of hippocampal acetylcholine release: a potent central action of interleukin-2. AB - The potential of the T-cell growth factor interleukin-2 (IL-2) to modulate the release of ACh from rat hippocampus was studied in vitro, as a means to investigate the possible functional significance of this cytokine in the CNS. Hippocampal slices were superfused with Krebs' buffer medium, and endogenous ACh released into the superfusate was measured using a radioenzymatic assay. Recombinant human IL-2 present during a stimulation with 25 mM KCl altered, in a concentration-dependent manner, the evoked transmitter release. At a concentration of 15 U/ml (< or = 1 nM), IL-2 inhibited ACh release by more than 50% of the control level (evoked ACh release from the untreated contralateral hemispheres). Inhibition was observed within 20 min of tissue exposure to IL-2 and lasted for up to 1 hr. The inhibitory effect of IL-2 was reversible since transient tissue exposure to IL-2 did not affect subsequent evoked ACh release. IL-2 at this concentration also significantly decreased evoked ACh in frontal cortical slices, but was ineffective in the parietal cortex and striatum, revealing that IL-2 selectively modulates the release of ACh from certain, but not all, cholinergic nerve terminals in the CNS. At very low concentrations (1.5 mU/ml, < or = 0.1 pM), IL-2 transiently increased hippocampal evoked ACh release, resulting in a biphasic dose-response profile with no significant effect observed at 0.015 mU/ml (< or = 1 fM). Other cytokines (IL-1 alpha, IL-3, IL-5, IL-6, interferon alpha), tested in hippocampal slice incubations, failed to modulate ACh release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340814 TI - Vacuole dynamics in growth cones: correlated EM and video observations. AB - The neuronal growth cone is a major site of surface membrane dynamics associated with uptake and release of materials, motility, and axon extension. Although intracellular membrane organelles are thought to mediate surface membrane addition and retrieval at the growth cone, membrane events are fleeting and therefore difficult to study directly. In an effort to capture transient interactions between intracellular membrane organelles and the plasmalemma at the growth cone, embryonic rat sympathetic neuron cultures were prepared for whole mount electron microscopy (EM) by rapid freezing and freeze substitution. We identified a set of vacuole-like organelles (> or = 150 nm in diameter) that appeared to interact directly with the plasmalemma. In stereo-pair EM images the bounding membrane of some of these vacuoles had an orifice at sites where the organelle was adjoining the plasmalemma, suggesting that the organelle and surface membranes were confluent. Since this population of organelles could be labeled with cationized ferritin or HRP when added to living cultures just prior to freezing or chemical fixation, they were probably derived from the plasmalemma. Combined light microscopy and EM of individual growth cones showed that these same vacuoles had a conspicuous reverse shadowcast appearance in differential interference contrast images. Thus, we used real-time video microscopy to follow these organelles in living growth cones. Many of these vacuoles spontaneously appeared, remained visible for several minutes, and then disappeared. Reverse shadowcast vacuoles were formed at various sites throughout the growth cone, including surface membrane ruffles at the leading edge [P (peripheral)-domain] as well as quiescent and retracting regions at the growth cone base [C (central)-domain]. Vacuoles in the P-domain moved centripetally and rarely grew in size. In contrast, those in the C-domain exhibited Brownian-like movements and sometimes appeared to increase in size, raising the possibility that new membrane may be added to these organelles. Vacuoles within both the P- and C-domains shrank before rapidly disappearing, but rarely vesiculated, suggesting that they had fused with the plasmalemma. The results indicate that vacuoles are a highly dynamic population of organelles that directly communicate with the plasma membrane at the growth cone; they provide a major route of surface membrane uptake and may also play a role in membrane recycling. PMID- 8340815 TI - A spiking network model of short-term active memory. AB - Studies of cortical neurons in monkeys performing short-term memory tasks have shown that information about a stimulus can be maintained by persistent neuron firing for periods of many seconds after removal of the stimulus. The mechanism by which this sustained activity is initiated and maintained is unknown. In this article we present a spiking neural network model of short-term memory and use it to investigate the hypothesis that recurrent, or "re-entrant," networks with constant connection strengths are sufficient to store graded information temporarily. The synaptic weights that enable the network to mimic the input output characteristics of an active memory module are computed using an optimization procedure for recurrent networks with non-spiking neurons. This network is then transformed into one with spiking neurons by interpreting the continuous output values of the nonspiking model neurons as spiking probabilities. The behavior of the model neurons in this spiking network is compared with that of 179 single units previously recorded in monkey inferotemporal (IT) cortex during the performance of a short-term memory task. The spiking patterns of almost every model neuron are found to resemble closely those of IT neurons. About 40% of the IT neuron firing patterns are also found to be of the same types as those of model neurons. A property of the spiking model is that the neurons cannot maintain precise graded activity levels indefinitely, but eventually relax to one of a few constant activities called fixed-point attractors. The noise introduced into the model by the randomness of spiking causes the network to jump between these attractors. This switching between attractor states generates spike trains with a characteristic statistical temporal structure. We found evidence for the same kind of structure in the spike trains from about half of the IT neurons in our test set. These results show that the behavior of many real cortical memory neurons is consistent with an active storage mechanism based on recurrent activity in networks with fixed synaptic strengths. PMID- 8340816 TI - Degradation of two AChR populations at rat neuromuscular junctions: regulation in vivo by electrical stimulation. AB - The effect of electrical stimulation on the stability of junctional ACh receptors (AChR) on soleus muscles of Wistar rats was compared to that of denervation and reinnervation. Denervation causes the degradation rate of the slowly degrading AChRs (Rs) at the neuromuscular junction to accelerate and be replaced by rapidly degrading AChRs (Rr), while reinnervation restabilizes the accelerated Rs. Electrical stimulation initiated at the time of denervation prevented the acceleration of the Rs. It could not, however, reverse the effect of denervation if initiated after the AChRs became destabilized, nor could it slow the degradation rate of the Rr. We conclude that electrical stimulation of denervated muscle downregulates the expression of the Rr and prevents the destabilization of Rs. PMID- 8340817 TI - Dopaminergic modulation of dye coupling between neurons in the core and shell regions of the nucleus accumbens. AB - The presence of dye coupling and electrotonic coupling within the nucleus accumbens was examined using intracellular recording and staining in rat brain slices. In 24% of the cells examined, injection of single accumbens neurons with the dye Lucifer yellow resulted in the complete labeling of more than one cell. To examine whether this coupling is regulated by dopamine (DA), the extent of dye coupling was assessed in the presence of dopaminergic agonists and antagonists. In the core region of the accumbens, D1 receptor stimulation induced a decrease in the incidence of dye coupling; this effect could be blocked by the D1 antagonists SCH 23,390 and SCH 39,166, by the D2 antagonist sulpiride, or by depletion of DA by reserpine and alpha-methyl-p-tyrosine coadministration, but not by the atypical antipsychotic drug clozapine. In contrast, in the posterior part of the shell region, D2 receptor stimulation increased the incidence of coupling independent of the state of D1 receptor activation. Fast spikelets resembling coupling potentials were found to occur only in neurons that also showed dye coupling, and could be attenuated in core neurons by D1 receptor stimulation. These findings suggest that DA, in addition to its actions on the membrane of single neurons, may also affect neuronal integration on a network level by regulating the transfer of information between adjacent neurons within the nucleus accumbens. PMID- 8340818 TI - Process outgrowth and synaptic varicosity formation by adult photoreceptors in vitro. AB - To assess the regenerative capability of the photoreceptor synapse, we have isolated and cultured photoreceptors from the mature salamander retina. Both rod and cone photoreceptors were able to regenerate processes within 3 d of plating. Cells extended numerous actin-containing filopodia as well as a few neuritic processes. The neurites contained microtubules and formed synaptic vesicle-filled varicosities, as shown by immunostaining for tubulin and synaptic vesicle proteins and by electron microscopy. Furthermore, regenerated varicosities were capable of depolarization-induced vesicle labeling, suggesting that they can recycle synaptic vesicles and release neurotransmitter by synaptic vesicle exocytosis. Differences were observed between rod and cone cell synaptic regeneration in vitro, which resembled structural differences between their synaptic terminals in situ: rod cells formed multiple synaptic vesicle-filled varicosities along neurites at a distance from the soma, whereas cone cells tended to accumulate synaptic vesicles within the soma. The regeneration of neurites and synaptic vesicle-filled varicosities was abolished by microtubule depolymerizing agents, suggesting a role for microtubule-based vesicle transport in the formation of varicosities. Finally, process outgrowth and varicosity formation were independent of cell-cell contact and, indeed, proceeded in the complete absence of other cells. These findings suggest not only that differentiated photoreceptors are capable of synaptic renewal but that the regeneration of presynaptic-like terminals is an intrinsic ability of rod and cone cells. PMID- 8340819 TI - Development of individual geniculocortical arbors in cat striate cortex and effects of binocular impulse blockade. AB - This study analyzes the morphological changes in geniculocortical axons terminating in the primary visual cortex of the cat, during the period in which, in normal development, the terminals in layer IV undergo an eye-specific segregation. Geniculocortical afferent fibers were filled anterogradely by the Phaseolus lectin (PHA-L) injected into the main laminae of the LGN. After standard immunohistochemical procedures, single axons were serially reconstructed in two or three dimensions. Experiments were performed in normal kittens and in kittens in which retinal activity was continuously blocked by repeated intraocular injections of TTX. In normal kittens, arbors were reconstructed at four different ages (19, 23, 30-31, and 39 days postnatally) spanning the period during which the geniculocortical projection segregates into eye-specific columns in layer IV (LeVay et al., 1978). Results reveal that sparse but widely extending branches characteristic of young arbors are eliminated during normal development at the same time as selected portions of the arbor grow considerably in length and complexity. The terminal arborizations also subdivide into distinct patches of terminals, consistent with the segregation of left and right eye afferents. In TTX-treated animals, axonal arbors reconstructed at postnatal days 23, 29, and 39 show a complexity and extent of terminal arborization similar to that of normal animals, though more variable in size and degree of elaboration. No progressive changes are evident with age. Further, the majority of arbors reconstructed from TTX-treated animals lack the patchy organization typical of normal animals. PMID- 8340820 TI - Diffusion of small solutes in cartilage as measured by nuclear magnetic resonance (NMR) spectroscopy and imaging. AB - The ability of water and solutes to move through the cartilage matrix is important to the normal function of cartilage and is presumed to be altered in degenerative diseases of cartilage such as osteoarthritis and rheumatoid arthritis. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) techniques were used to measure a self diffusion coefficient (D) for small solutes in samples of explanted cartilage for diffusion times ranging from 13 ms to 2 s. With a diffusion time of 13 ms, the intratissue diffusivity of several small solutes (water, Na+, Li+, and CF3CO2-) was found consistently to be about 60% of the diffusivity of the same species in free solution. Equilibration of the samples at low pH (which titrates the charge groups so that the net matrix charge of -300 mM at pH 8 becomes approximately -50 mM at pH 2) did not affect the diffusivity of water or Na+. These data, and the similarity between the D in cartilage relative to free solution for water, anions, and cations, are consistent with the view that charge is not an important determinant of the intratissue diffusivity of small solutes in cartilage. With 35% compression, the diffusivity of water and Li+ dropped by 19 and 39%, respectively. In contrast, the diffusivity of water increased by 20% after treatment with trypsin (to remove the proteoglycans and noncollagenous proteins). These data and the lack of an effect of charge on diffusivity are consistent with D being dependent on the composition and density of the solid tissue matrix. A series of diffusion weighted proton images demonstrated that D could be measured on a localized basis and that changes in D associated with an enzymatically depleted matrix could be clearly observed. Finally, evidence of restriction to diffusion within the tissue was found with studies in which D was measured as a function of diffusion time. The measured D for water in cartilage decreased with diffusion times ranging from 25 ms to 2 s, at which point the measured D was roughly 40% of the diffusivity in free solution. Although changes in matrix density by compression or digestion with trypsin led to a decrease or increase, respectively, in the measured D, the functional change in measured diffusivity with diffusion time remained essentially unchanged. In a different type of study, in which bulk transport could be observed over long periods of time, cartilage was submerged in 99% D2O and MRI studies were performed to demonstrate the bulk movement of water out of the cartilage matrix.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8340821 TI - Pleiotrophin is an abundant protein in dissociative extracts of bovine fetal epiphyseal cartilage and nasal cartilage from newborns. AB - An abundant protein that is identical to the growth-associated protein pleiotrophin (PTN) has been isolated from dissociative extracts of bovine nasal and fetal epiphyseal cartilage. The yield from these tissues was at least 15 micrograms/g wet weight of cartilage. PTN was absent or was present only in trace amounts in mature articular cartilage. An analysis of tryptic fragments of PTN, held together with disulfide bonds, did not indicate any set pattern of cystine cross-links, which suggests a propensity for rapid refolding of the protein. PTN could not be isolated from thin (10 microns) slices of nasal cartilage in physiological extraction buffers, which indicates that it was tightly associated with the cell surface, was tightly associated with nonextractable matrix, or was an intracellular protein. Its appearance in various extraction media parallels that of histone H2b, a nucleosomal protein; this suggests a possible intracellular location for the protein. Immunohistochemical analysis of its distribution in fetal epiphysis indicated that it is associated with chondrocytes. PMID- 8340822 TI - In vivo quantification of proteoglycan synthesis in articular cartilage of different topographical areas in the murine knee joint. AB - We developed a method of quantitative measurement of the synthesis of proteoglycans in different areas of the patella and the tibial plateau of the mouse. After incorporation of radioactive sulfate in vivo, the patella was divided with a punch into a central and a peripheral part. A central medial and a central lateral part were taken from the tibial plateau to measure the synthesis of proteoglycans. The synthesis was determined in normal joints and at different intervals after intra-articular injection of sodium iodoacetate and was compared with autoradiographs of whole joint sections. Although considerable variation in sulfate incorporation was found within a group on particular days after induction of osteoarthritis, the variation among experiments was low. Comparison with autoradiographs showed that this new method makes it possible to quantify proteoglycan synthesis by incorporation of radioactive sulfate in different topographical areas of the murine knee joint. PMID- 8340823 TI - Adaptive bone remodeling around bonded noncemented total hip arthroplasty: a comparison between animal experiments and computer simulation. AB - Severe loss of bone related to stress-shielding is one problem threatening the long-term integrity of noncemented total hip arthroplasty. It is widely accepted that this phenomenon is caused by adaptive bone remodeling according to Wolff's law. Recently, quantitative bone-remodeling theories have been proposed, suitable for use in computer-simulation models in combination with finite-element codes, which can be applied to simulate the long-term effect of the remodeling process. In the present paper, the results of such a computer simulation are compared with those in an animal experiment. A three-dimensional finite-element model was constructed from an animal experimental configuration concerning the implantation of a fully coated femoral hip prosthesis in dogs. The simulation results of the adaptive bone-remodeling process (geometric adaptations at the periosteal surface and density adaptations within the cancellous bone) were compared with cross sectional measurements of the canine femurs after 2 years of follow-up. The detailed comparison showed that long-term changes in the morphology of bone around femoral components of total hip replacements can be fully explained with the present quantitative adaptive bone-remodeling theory. PMID- 8340824 TI - Evaluation of bone-grafting materials in a new canine segmental spinal fusion model. AB - This paper describes a new canine segmental spinal fusion model for the comparison of bone-grafting materials. The test sites in the model are three separate posterior interfacet-interlaminar fusion sites in the lumbar spine (L1 2, L3-4, and L5-6). The outcome was assessed by scoring of the fusion sites for union and by mechanical testing of fused segments. The results from two experiments are presented. Autogenous cancellous bone was the most effective material tested and had a statistically superior score for union compared with all other materials (p = 0.01). The results with an osteoconductive matrix of collagen and ceramic alone were no better than those with the controls (no graft). However, addition of an extract of matrix-derived proteins (15-30 kDa) to the collagen-ceramic carrier appeared to improve the score for union. The inclusion of nonresorbed ceramic granules had no evident effect on the mechanical properties of fusions, with a comparable score for union. This model appears to be a sensitive and efficient method for the comparison of graft materials. Advantages over previously described models are discussed. PMID- 8340825 TI - Posture affects motion coupling patterns of the upper cervical spine. AB - Measurements of motions of the cervical spine are used to help diagnose the problems of clinical instability due to degenerative changes and trauma. For a better interpretation of the three-dimensional motions of the upper cervical spine, knowledge of the effects of posture on these motions is necessary. Seven fresh human cadaveric C0-C3 spinal specimens were utilized. Each specimen was put in three distinct sagittal plane postures: full flexion, neutral, and full extension. At each posture, two load types were applied: left and right axial torques, and left and right lateral bending moments up to 1.5 Nm. The resulting three-dimensional relative motions of C0-C1 and C1-C2 were measured, with use of nonconstraining stereophotogrammetry, in the form of load-displacement curves. We found that the curves were nonlinear. The most dramatic change due to modification in posture was found in coupled sagittal plane rotation, which changed from extension at extended posture to flexion at flexed posture at both levels and in response to both load types. For the axial torque, the main axial rotation and coupled lateral bending changed little with posture. For the lateral bending moment, the main lateral bending rotation and coupled axial rotation decreased; the latter changed direction at C1-C2 as the spine was put into flexed posture. The motions for the right and left load applications generally were mirror images, except for the coupled sagittal plane rotations, which did not change with the direction of the load. PMID- 8340826 TI - Changes in bone in a model of spinal cord injury. AB - Bone calcium, histomorphometry, and mechanical strength were evaluated in a model of spinal cord injury. Cortical bone area and rates of formation and apposition at the tibiofibular junction (TFJ) and midshaft of the humerus were measured at 35-42, 42-77, and 77-94 days after transection of the spinal cord. All comparisons were between the animals with a spinal lesion and control animals. A 0.34% difference in the length of the tibia of the two groups of animals was observed, the dry weight of the tibia was 28.4% less in rats with a lesion, and there was no significant difference in the amount of calcium per milligram of bone. At 35 days after surgery, the cortical area in the midshaft of the humerus was slightly less (11%) in rats with a lesion, but by 94 days there was no difference in cortical or medullary area. The final (day 94) cortical area at the TFJ in rats with a lesion was less than that in the controls. Bone formation at the TFJ was similar in both groups in the period of 35-42 days and was similar at 77-94 days in the animals with a lesion, and rates of formation and apposition were greater in the humerus of rats with a lesion; the rates did not differ significantly between groups at either site. At 94 days, trabecular bone area in the tibial metaphysis was 41% less in rats with a lesion. Mechanical parameters were significantly less in the femora, but not the humeri, of rats with a lesion. PMID- 8340827 TI - Effect of controlled local release of sodium fluoride on bone formation: filling a defect in the proximal femoral cortex. AB - To assess the effect of sodium fluoride (NaF) in the healing of a defect in cortical bone, an experimental model was created by the drilling of 5.0 mm holes in the proximal ends of both femora of 12 adult male New Zealand White rabbits. An interlocking intramedullary implant constructed of poly(d,l-lactic acid) containing NaF was placed in the right femur and an identical implant without NaF (sham), in the left. The implant in the right femur was designed to release NaF in a controlled manner over the duration of the experiment. Ten weeks after implantation, the specimens were removed and were tested in torsion. The mechanical properties were not significantly different between the groups. The femora exposed to NaF had an 18.6% increase in intact cortex near the defect (p = 0.023), however, the deposition of mineralized bone within the defect was not significantly greater. In fact, healing appeared to be impaired by the presence of NaF. There was complete closure of the defect in all but one of the femora with a sham implant, but the tissue had not yet calcified. In contrast, only one femoral defect exposed to NaF had closed. Examination of the material filling the defects of the femora exposed to NaF showed that it was predominantly uncalcified osteogenic mesenchymal tissue. PMID- 8340828 TI - Effects of transforming growth factor beta on cells derived from bone and callus of patients with osteogenesis imperfecta. AB - We studied the influence of transforming growth factor beta (TGF-beta) on cultured bone cells derived from two patients with osteogenesis imperfecta (OI) and from human controls. Additionally, cells from a hyperplastic callus that had developed spontaneously at the femur of the patient in Case 1 and cells from a normal fracture callus were included in the study. TGF-beta increased the synthesis of total protein and collagen of all cells without changing the pattern of interstitial collagens. Proliferation was stimulated by TGF-beta in the OI bone cells from Case 1, in cells from the central part of the hyperplastic callus, and in cells from the fracture callus. In Case 2, proliferation of bone cells was decreased by low concentrations of TGF-beta. Alkaline phosphatase (AP) activity was enhanced by TGF-beta in normal human bone cells, not affected in bone cells from the patient in Case 2 or in cells from the central part of the hyperplastic callus, and inhibited in bone cells and cells from the peripheral part of the hyperplastic callus of Case 1 and in cells from the fracture callus. We conclude that TGF-beta has common and specific effects on cultured human cells derived from different types of skeletal tissues. Simultaneous stimulation of collagen synthesis and AP activity by TGF-beta was restricted to normal human bone cells and might reflect their mature state of osteoblastic differentiation. Cells derived from bone of both patients with OI, from the hyperplastic callus, and from the fracture callus showed a different response pattern to TGF beta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340829 TI - Laser Doppler flowmetry for estimation of bone blood flow: studies of reproducibility and correlation with microsphere technique. AB - The blood flow in the femoral condyles of six pigs was measured by the microsphere technique and by laser Doppler flowmetry (LDF) before and after clamping of the external iliac artery. A significant decrease in the bone blood flow was found with both microsphere and LDF measurements, and a high correlation was found between the two methods. After release of the arterial clamp, the LDF values rapidly returned to approximately the same values as before clamping. In a second part of the study, the LDF output signal was studied in the intertrochanteric area of eight patients. The reproducibility of two LDF measurements at the same location was within 15%. The temporal variability of the LDF signal during 10 min of recording showed only slight variations. It is concluded that LDF is relative in nature and that the mean LDF output signal is suitable for monitoring dynamic responses of the bone blood flow to various stimuli. Several consecutive measurements have to be performed if the blood flow at different locations of a specific bone are to be compared with each other. PMID- 8340830 TI - Cellular shape and pressure may mediate mechanical control of tissue composition in tendons. AB - In vivo studies have suggested that mechanical factors are involved in the regulation of the morphology and biochemical composition of tendons that wrap around bones. In these tendons, fibrocartilage is found in the segment wrapped around the bone, and tendon far from the bone displays normal tendon histomorphology. Recent in vitro studies have shown that intermittently loaded connective tissue cells are sensitive to changes in cellular shape and hydrostatic pressure: stretching and distortion of the cells enhances production of fibrous matrix and hydrostatic pressure enhances production of cartilaginous matrix. We used finite-element analysis to determine whether the regions of increased development of cartilaginous matrix in tendons that wrap around bones correspond to regions in which tendon cells are subjected to higher pressures, and whether the maintenance and rearrangement of fibrous extracellular matrix in these tendons is associated with regions of stretching and distortion of cells. We found that regions of cartilaginous matrix and fibrous matrix formation and turnover correlate well with patterns of hydrostatic compressive stress and distortional strain in the tendon. Although further experiments clearly are needed to establish the predictive value of our approach, hydrostatic stress and distortional strain history--parameters intimately related to changes in cellular pressure and shape, respectively--appear to be important tissue-level mechanical stimuli that regulate cartilaginous and fibrous matrix composition of connective tissues. PMID- 8340831 TI - Effects of complete stress-shielding on the mechanical properties and histology of in situ frozen patellar tendon. AB - The effects of freezing and stress-shielding on the mechanical properties and histology of the patellar tendon (PT) were studied with the use of 28 mature Japanese white rabbits. The PT was frozen in situ by liquid nitrogen to kill the fibroblasts and then, for stress-shielding, a stainless-steel wire, installed between the patella and the tibial tubercle, was stretched to release all tension in the PT. After being allowed unrestricted activity in their cages for 1, 2, 3, or 6 weeks, the animals were killed, and the PTs were excised for mechanical and histological study. The cross-sectional area of the frozen and stress-shielded PT started to increase significantly 1 week after the treatment and leveled off at 3 weeks. In contrast, the tensile strength and elastic modulus began to decrease significantly at 1 week, falling to 15% of the control values at 6 weeks. Histologically, cells were absent until 2 weeks after freezing and stress shielding, although new cells appeared by 3 weeks. Splitting and fragmentation of collagen bundles were observed beginning at 2 weeks. These results indicate that complete stress-shielding led to substantial changes in the mechanical properties of the once-frozen PT, even in the absence of the tissue remodeling process by fibroblasts. PMID- 8340832 TI - In vitro biomechanical analysis of suture methods for flexor tendon repair. AB - This study was designed to compare five different suture methods that are used clinically for tendon repair. The flexor digitorum profundus tendons from the digits of adult mongrel dogs and adult human cadavers were used as models. The tendons in zone II of the hand, defined as the region from the distal palmar crease to the insertion of the flexor digitorum superficialis tendon at the middle phalanx, were transected and then were repaired by one of the suture methods developed by Kessler, Tsuge, Tajima, Savage, or Lee. The gliding function and tensile properties of the repaired tendons were evaluated biomechanically at time zero. The Tajima and Savage methods produced better gliding function than the other techniques. In the canine specimens that had been repaired by one of these two methods, the rotation of the distal interphalangeal joint was more than 60% of the rotation of the canine control specimens; only the Savage technique produced a rotation 124% that of the human control specimens. After the Tajima repair, the rotation of the proximal interphalangeal joint was 113% that of the canine control specimens and 157% that of the human controls. In the canine specimens that had had the Tajima or Savage repair, excursion of the tendon was greater than 55% that of the controls. The tendons repaired by the Savage method tolerated a significantly higher ultimate load to failure (14 and 25% that of the canine and human control specimens, respectively) than the other methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340833 TI - Method to determine collagen density distributions in fibrous tissues. AB - We present a method for the measurement of hydroxyproline density distributions, as an estimate for collagen density distributions, in fibrous tissues such as ligaments and tendons. To evaluate this method, a single flexor tendon of a human hand was divided into seven tissue locations. Triplicate determinations of the dry weight tissue mass, volume, and hydroxyproline mass were made at each location: two samples were analyzed at the same time (a and b) and one was analyzed later (c). The intralocation variation is an estimate for the measurement error variance, which indicates both the precision (a compared with b) and the repeatability (b compared with c) of the technique for determination of volume, dry weight tissue mass, hydroxyproline concentration, and hydroxyproline density. The precision was about 5% for all variables, and the repeatability ranged from 1.5-4.3%. In comparison with the interlocation variations, the error variances were small, except for collagen concentration. This indicates that despite the measurement errors, differences in hydroxyproline density can be detected within fibrous tissues with the proposed method. The use of only a single tendon is adequate to evaluate the measurement error of the method, but more tendons should be measured to generalize the absolute values of the variables. PMID- 8340834 TI - Declining drug use in relation to increased drug education: a trend study 1979 1991. AB - During the 1980s alcohol and drug education increased in Ontario schools, especially at the Grade 7 level. This article reports aggregate relationships between increased levels of exposure to classroom alcohol, tobacco, and cannabis education, and the use of alcohol, tobacco, and cannabis by students in Ontario schools. The data were derived from repeated cross-sectional probability surveys of alcohol and drug use conducted every two years since 1979. There were strong inverse associations between increases in exposure to alcohol and drug education and reported levels of use of these substances, especially for alcohol and for Grade 7 students. PMID- 8340835 TI - Who receives drug education in our schools?: a paradox. AB - Data from a national survey by the United States Department of Justice of 47,000 households reveals a paradox regarding who receives drug education in primary and secondary schools. Those who would seem to need it the most are least likely to receive it. Thus, blacks receive drug education classes less often than whites, students in central city classes less often than those in other regions, and students who report that drugs are available are also less likely to receive drug education classes than students who report that drugs are not available. The results are paradoxical, but consistent with a study by Denson, Voight, and Eisenman which found that predominantly black schools in Louisiana provided less AIDS education than predominantly white schools. PMID- 8340836 TI - Reducing substance abuse risk factors among children through a teacher as facilitator program. AB - A Teachers as Facilitators (TAF) Program used classroom teachers as leaders of small groups that promoted social, emotional, and academic development of children at high risk of adopting potentially destructive substance abuse patterns. The program was intended to increase participating students' positive socialization experiences and academic achievement by successfully integrating these students into the school's social system. A longer-range goal was to increase students' sense of worth as it affects their attitudes toward relationships with other people and academic demands. Program results were: 1) school personnel were found capable of accurately identifying and referring to the TAF Program children who were at risk of substance usage and in need of assistance; 2) the TAF Program was effective in improving at-risk students' perceived academic self-concept, but was less effective in increasing students' perceived sense of social support; and 3) the program was endorsed by participating teachers, counselors, and administrators. PMID- 8340837 TI - Two-step drug education in Norway. AB - A survey of drug education in Norwegian lower secondary schools showed that almost one-fourth of the programs were based on a two-step model, which is described in this article. The intensive courses were socially successful, and created motivation, enthusiasm, and changes of attitudes. More than 90 percent of the participants carried out the second step of the teaching. There were important differences from one school to another in regard to how the pilot pupils, and their teaching program, were received. They found it difficult to find sufficient time for their programs, and sometimes hard to keep their classmates in order. Most of the classmates found the teaching in the second step interesting, but they had little belief in the preventive effect. PMID- 8340838 TI - Sexual abuse and drinking and drug use: implications for prevention. AB - Based on a survey of adolescent females in grades seven through twelve in a suburban school system, the relationship between drinking, drug use, and sexual abuse is examined. Using a holistic approach to adolescent deviant behavior, connections between family, peer, psychosocial factors and drug use and delinquency are explored. Girls who report sexual molestation are more likely to have used a number of drugs, different from the prevalence profile of the larger sample. Significant correlations for younger girls between sexual molestation and delinquency are also reported. Implications for school based drug prevention programs are discussed. PMID- 8340839 TI - Social bonds, early trauma and smoking: evidence of the group specific relevance of control theory. AB - This study analyzes data from a national sample of 595 adults to simultaneously evaluate the potential effects of social bonds and childhood trauma on tobacco smoking. Although both control factors and childhood experiences were found to affect smoking, religious belief and belief in the importance of conforming to moral and social norms had more important and robust negative relationships to smoking than commitment, attachment, or involvement social bonds. But, whereas childhood trauma appeared to promote smoking among both college educated and less educated persons, control factors significantly inhibited smoking only among the less educated. Implications for future drug research as well as anti-smoking campaigns and other anti-drug programs are discussed. PMID- 8340840 TI - On the role of patient. AB - Modern, highly technical health care systems increasingly remove patients from active participation in managing their own medical treatment. This is particularly true when serious or life-challenging illness occurs. Health psychology has much to contribute in the debate over the degree of patient self determination necessary to achieve optimal treatment outcomes. Psychologists may directly influence this process through their professional contact with medical patients and their families. Through researching the behavioral skills of medical consumership, identifying the elements of effective patient-physician interaction, and encouraging physicians-in-training to adopt a propatient partnership attitude, psychology adds new dimensions to the provision of health care. This paper reviews some of the issues faced by patients with life challenging illnesses through the writer's personal experience, and seeks to identify the requisite actions for informed, participatory involvement on the part of patients. PMID- 8340841 TI - Psychological research in pediatric oncology. PMID- 8340842 TI - Neuropsychological effects of central nervous system prophylactic treatment in childhood leukemia: methodological considerations. AB - Reviewed 53 studies on the effects of central nervous system prophylactic treatment (CNSPT) on cognition and neuropsychological functioning. CNSPT involves irradiation and/or chemotherapy directed to the brain, and is frequently administered to children who have leukemia. The effects of CNSPT on neuropsychological functioning in long-term cancer survivors remains controversial. A number of studies failed to identify any neuropsychological impact secondary to CNSPT, whereas others reported deficits that appear to be a function of CNSPT. Several methodological issues that make it difficult to draw meaningful conclusions from this research literature are identified and discussed. Specific recommendations are made for improvements in research on CNSPT in children. PMID- 8340843 TI - Factors associated with social and behavioral problems among children recently diagnosed with brain tumor. AB - Compared the psychological adjustment of 81 children with brain tumors to that of 31 control children with various malignancies not involving the central nervous system. Both groups exhibited significantly increased frequencies of elevations on one or more age- and gender-corrected Social Competence and Behavior Problems scales of the Child Behavior Checklist (CBCL) relative to normative expectations. Comparison of the Brain Tumor and Cancer Control groups revealed no significant differences on any CBCL scale. Among children diagnosed with brain tumors, stepwise multiple regression analyses revealed that low child IQ, residence in a single-parent family, moderate to severe disfigurement, low SES, tumor location, and severe functional impairment were associated with decreased Social Competence scores. Elevated Behavior Problems scores were associated with younger maternal age at the child's birth, tumor location, and residence in a single-parent family. Results reinforce the need to consider complex relationships between demographic characteristics of the child's family, type of brain damage, and the cosmetic and functional status of the child in determining acute psychological adjustment of brain-damaged children. PMID- 8340844 TI - Adjustment in the peer system of adolescents with cancer: a two-year study. AB - Evaluated the psychosocial adaptations of adolescents with cancer who were primarily off treatment (n = 19, ages 11-18) as compared with matched classroom controls in a 2-year longitudinal study on indices of (a) teacher, peer, and self perceptions of social reputation; (b) multiple measures of popularity and friendships; and (c) self-reported feelings of loneliness, depression, and self concept. Adolescents with cancer continued to have a social reputation as being more socially isolated, but no significant differences were identified on multiple measures of social acceptance or the self-reported feelings. In general, adolescents with cancer were similar to peers on numerous dimensions of psychological functioning manifesting minimal discernable psychosocial late effects. PMID- 8340845 TI - Parents of children newly diagnosed with cancer: anxiety, coping, and marital distress. AB - Evaluated anxiety, approach-avoidance coping style, and marital distress in 134 parents of children with cancer shortly after diagnosis. Of the 67 marital pairs studied, approximately 25% of the mothers and 28% of the fathers reported significant marital distress. Regression analyses revealed that marital distress was predicted by a combination of general emotional distress, the discrepancy between the couple's state anxiety levels, and the couple's use of sensitizing coping strategies. Greater differences in anxiety levels between the parents and greater stimulus approach coping activity in the marriage were associated with greater reported marital distress. PMID- 8340846 TI - Goal-directed behavior and perception of self-competence in children with spina bifida. AB - Compared a group of school-age children with spina bifida (n = 15) between the ages of 6 and 12 years with an age- and IQ-matched control group of normal children (n = 15). As predicted, the spina bifida children spent less time using goal-directed behaviors and more time in simple manipulation of the toys compared to the normal children. There were no group differences between the spina bifida and normal children's perceived competence but parents of the spina bifida children rated their children as having lower cognitive and physical competence. Associations were found between goal-directed behaviors and perceived self competence for children in the spina bifida group but not the normal group. PMID- 8340847 TI - Parental anxiety and response to symptoms of minor illness in infants. AB - Examined the relationship between parental anxiety and parental contact with the clinic following a child's initial DPT immunization. The subjects were 80 volunteer mothers who brought their 8-week-old infants to an outpatient clinic for a well-child visit. At the time of the visit, maternal anxiety, anxiety proneness, perception of the infant as fussy or difficult, and demographic information were assessed. Seventy-two hours after the immunization, subjects reported DPT side effects and physician contacts. Discriminant function analysis found that mothers who were anxious prior to DPT administration and who had infant girls were more likely to contact the clinic by telephone. This relationship was independent of prior maternal experience with DPT immunization, maternal perception of the infant's general fussiness, and maternal Trait anxiety. PMID- 8340848 TI - Neonatal surgery: intensive care unit versus operating room. AB - The critically ill neonate with a surgical condition requires transfer to an operating room (OR), a process which may be associated with significant morbidity. In an effort to reduce such morbidity, we performed surgery on critically ill neonates in a designated area of our neonatal intensive care unit (NICU) over the past 4 years and have compared the outcome for infants operated on within the NICU with infants operated on in the OR over the same period. There were 81 procedures performed in the NICU compared with 112 in the OR. Infants operated on in the NICU had lower birthweights (1,758 g v 2,457 g), lower gestational ages (31.3 weeks v 35.8 weeks), and lower presurgical weights (2,118 g v 2,922 g) (all P < .0001). In addition, infants operated on in the NICU had a greater severity of illness with 78% requiring mechanical ventilation versus 26% for the OR group (P < .0001) with a higher presurgical FiO2 (.43 v .31, P = .005), and a higher presurgical mean airway pressure (8.0 cm H2O v 6.2 cm H2O) for infants requiring mechanical ventilation. The overall mortality was higher in the NICU group (14% v 2%), reflecting their underlying prematurity, illness, and anomalies. There was only one surgically related death, which occurred in the NICU group. There was no significant difference in culture-proven sepsis, length of surgery, change in weight, temperature, blood pressure, heart rate, FiO2, mean airway pressure, or oxygen index associated with surgery, but there was a significantly higher incidence of hyperthermia with a temperature of greater than 37.5 degrees C in the OR group (17.8% v 3.7%, P = .002). Our experience suggests that surgical procedures can be performed in the NICU for the unstable critically ill neonate with a morbidity comparable to that seen in the OR. Further experience is needed to compare the risks and benefits of this approach. PMID- 8340849 TI - Gastroschisis: an 18-year review. AB - From 1972 to 1990, 69 cases of gastroschisis were treated at Akron Children's Hospital Medical Center. Eighty-one percent of these patients underwent primary closure of their abdominal wall defect. Thirteen of 69 patients (19%) required Silastic silos with final closure in an average of 7.8 days. There was no sex predilection, the average birth weight was 2,473 g, and the mean gestational age was 36.3 weeks. Twenty-six percent had associated anomalies, the majority were intestinal atresia, volvulus, and/or undescended testicles. Seventy-seven percent of the infants were delivered vaginally. Fourteen children were delivered via cesarean section. Seven cesarean sections were done solely for prenatal ultrasonic identification of an abdominal wall defect. There was no improvement in hospital stay, complications, days until enteral feeds were tolerated, days intubated, or number of surgical procedures in this group. In 14 patients, mesh sheeting (Marlex, Silastic) was used in the final closure. Sixty-four percent of these incurred wound breakdown necessitating removal of the mesh. This compares with a 3.2% wound breakdown in the nonmesh group. The average hospital stay was 43.9 days and the average time to enteral feeds 20.2 days. Sixty-four percent of the patients required postoperative intubation for an average of 5.5 days. The overall mortality rate was 4.3%. The present data do not support gastroschisis alone as an indication for cesarean section. The data indicate that mesh be avoided in the final closure if possible and support a favorable prognosis for most babies. PMID- 8340850 TI - Large gastroschisis: primary repair with Gore-Tex patch. AB - The author reports four newborns with large gastroschisis, in whom primary fascial closure could not be accomplished. They were successfully treated by primary repair with Gore-Tex patch. Gore-Tex patch closure is a safe and good alternative in large abdominal wall defects when primary fascial repair is not feasible. PMID- 8340851 TI - Gastroschisis in the partially extraamniotic fetus: experimental study. AB - The short, thick, matted bowel, often found in gastroschisis, has been attributed to a variety of factors. We designed an original animal model in order to isolate the effect of amniotic fluid on the fetal bowel. We created experimental gastroschisis in fetal rabbits. Extruded bowel was kept out of the amniotic sac in half of the operated fetuses. At term, 7 days after surgery, 21 surviving fetuses (12 intraamniotic gastroschisis [IAG] and 9 extraamniotic gastroschisis [EAG]) and 16 control littermates were collected for study. Five parameters were measured in each animal: body weight, intestinal weight, intestinal length, bowel diameter, and bowel wall thickness. Fetal mortality due to the extraamniotic fixation technique was 25%. We found no statistically significant difference in body weight, intestinal weight, or bowel wall thickness. An enormous difference was found in intestinal length (P < .0001 among the three groups). Bowel diameter was significantly different (P = .02) in the extreme groups (IAG and controls), with the intestine being more dilated in IAG than in EAG and controls. Gastroschisis in the absence of amniotic fluid was not as damaging to the fetal intestine as "natural" intraamniotic gastroschisis. PMID- 8340852 TI - A new bioprosthesis in large abdominal wall defects. AB - A collagen-coated Vicryl mesh bioprosthesis was used to repair a 4 x 4 cm full thickness abdominal wall defect, created in experimental rats. The tensile strength of the repair at 6 months reached 70% of the original abdominal wall. Implant collagen could not be differentiated from host collagen after 2 weeks. The increase in collagen content of the repair was responsible for the increasing tensile strength of the wound with time. All histological sections showed good tolerance of the implant. These results support the use of collagen Vicryl membrane to repair large abdominal wall defects. Clinical trials are indicated. PMID- 8340853 TI - Impaired respiratory function in infants with anterior abdominal wall defects. AB - Respiratory function at follow-up was assessed in 13 infants who had undergone surgical repair of an anterior abdominal wall defect. Six infants had exomphalos and seven had gastroschisis. The infants were delivered at a median gestational age of 36 weeks (range, 32 to 38 weeks). Respiratory function was assessed by measurement of functional residual capacity (FRC) at a median postnatal age of 5 months (range, 1 to 10 months). Although there was no significant difference in the FRC of the infants with gastroschisis compared with those with exomphalos, the study group's mean FRC (25 mL/kg) was significantly lower than that of 50 healthy control infants (mean, 30 mL/kg; 95% CI, +/- 6 mL/kg). Five infants had an FRC below the 95% confidence limit of the normal range. These data suggest that infants with anterior abdominal wall defects may have impaired antenatal lung growth. PMID- 8340854 TI - Lyophylized dura patch repair of congenital diaphragmatic hernia: occurrence of relapses. AB - During an 8-year period, 71 neonates with congenital diaphragmatic hernia were admitted to the Sophia Children's Hospital. Seventeen patients died before surgery. The other 54 patients underwent either direct suture (18) or patch closure with lyophylized dura (36), depending on the size of the defect. Forty patients survived. In 16 of them the defect was closed by direct suturing. In the other 24 patients a patch was used. Five recurrences of the defect occurred, all of them among the latter group. PMID- 8340855 TI - Extracorporeal membrane oxygenation in the management of cardiac failure secondary to myocarditis. AB - While most patients with viral myocarditis have a relatively uncomplicated clinical course, a small number of patients will present with cardiogenic shock unresponsive to standard medical therapy. We describe the clinical course of three patients who developed profound cardiac failure secondary to a documented viral myocarditis. Each patient was managed using venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support using the right common carotid artery/internal jugular vein for cannulation. While undergoing ECMO support, each patient developed elevated left-sided cardiac chamber pressures with resultant pulmonary edema. This was managed by balloon atrial septostomy in two cases and combined blade/balloon atrial septostomy in one case. Excellent decompression of the left heart was achieved in each patient. Two patients were successfully weaned from ECMO and are currently alive, with one demonstrating residual cardiac dysfunction. One patient developed global myocardial necrosis and ultimately died. This small series demonstrates a role for ECMO in the management of cardiac failure due to acute viral myocarditis unresponsive to medical therapy. Our experience also suggests that balloon atrial septostomy may be useful to decompress the left atrium and ventricle of patients with acute myocarditis while on ECMO. PMID- 8340856 TI - Motility function of the esophagus before primary anastomosis in esophageal atresia. AB - Two patients with a long gap esophageal atresia without tracheoesophageal fistula underwent an esophageal manometric study before primary anastomosis and one of them underwent an identical study after operation. Before operation both patients showed peristaltic contraction in the proximal esophagus when swallowing which was always followed by a coordinated contraction of the distal esophagus the same as in that of the normal esophagus. These peristaltic contractions induced a reflex relaxation of the lower esophageal sphincter (LES). After operation the manometric studies of the repaired esophagus demonstrated an abnormal esophageal motility, with simultaneous contractions occurring when swallowing in the proximal to the distal esophagus. In addition, the reflex relaxation of LES was incomplete. These data suggest that even if the intraluminal continuity is defective, the esophageal motility function is not disturbed in the proximal to distal esophagus in preoperative esophageal atresia, and that intraoperative mobilization and denervation may be suggested to be an important factor in esophageal dysmotility even when esophageal atresia is successfully repaired. PMID- 8340857 TI - Emergency center arteriography in the evaluation of suspected peripheral vascular injuries in children. AB - During the 6-year period from 1983 to 1989, 109 children aged 3 to 18 years (mean, 16) with suspected peripheral vascular injuries underwent 113 emergency center arteriograms (ECA) performed by hand injection of contrast material using a single roentgenographic film. The most common indication for ECA was the proximity of the injury in 93 (82.3%) of the cases as penetrating injury accounted for 106 (94%) of the cases. There were 89 true-negative, 14 true positive, 1 false-negative, and no false-positive arteriograms. The remaining 9 arteriograms were either equivocal or technically inadequate. The sensitivity, specificity, and diagnostic accuracy of this procedure were 98.9%, 100%, and 91.2%, respectively. Operative intervention was required for 9 (64.2%) injuries detected by emergency arteriography. The remaining 5 injuries were considered minor and were observed with no complications during a period of 21 months. Sixty eight children (76.4%) with negative ECA were followed for a mean of 12 months with no vascular complications or growth abnormalities noted. ECA is a rapid, accurate, and cost-effective technique. It is of particular value in detecting the presence of occult arterial injuries that might have deleterious effects in the growing child. PMID- 8340858 TI - Elective surgery in children with sickle cell disease without preoperative blood transfusion. AB - It is generally recommended that patients with sickle cell disease receive red blood cell (RBC) transfusions before undergoing general anesthesia and surgery. Since RBC transfusions are costly, inconvenient, and may cause serious complications, it might be useful to identify groups of patients for whom they are not absolutely necessary. We report our experience with 54 pediatric patients undergoing 66 elective surgical procedures without preoperative transfusion preparation. All patients were felt to be clinically and hematologically stable in the immediate preoperative period. For the majority of procedures (57/66, 86%) no transfusions were administered at any time during the perioperative course. There were no intraoperative complications or postoperative deaths. Overall, some type of postoperative complication was encountered after 17 procedures (26%). Complications were usually minor and were more likely to occur after procedures involving thoracotomy or laparotomy (10/20, 50%) and tonsillectomy/adenoidectomy (T&A) (5/9, 56%) than other procedures (2/37, 5%; P < .001). Pulmonary complications were especially more prevalent in the group undergoing thoracotomy, laparatomy, or T&A (9/29 v 0/37 for all other procedures, P < .001). We conclude that preoperative transfusions might be avoided in children with sickle cell disease who undergo most minor surgical procedures on an elective basis. Patients undergoing thoracotomy, laparotomy, or T&A are at a relatively higher risk of developing postoperative complications and would comprise ideal groups for evaluation of preoperative transfusion regimens in prospective carefully controlled, randomized studies. PMID- 8340859 TI - Partial splenectomy in Gaucher's disease: follow-up report. AB - This is a follow-up report of three children who had partial splenectomy and are suffering from Gaucher's disease. A few years following partial splenectomy in every patient, the remaining spleen enlarged and hypersplenism reappeared; partial splenectomy did not prevent bone destruction if it already existed before partial splenectomy. Treatment with Ceredase parallel with partial splenectomy may have theoretical and practical advantages. PMID- 8340860 TI - Pediatric laparoscopic splenectomy. AB - We report our initial experience and describe the operative technique used in three patients who underwent laparoscopic splenectomy for hematologic disorders between September 1991 and February 1992. No early or late complications have been found at an average follow-up of 9 months. All have remained asymptomatic and continue to have normal cell counts. We believe that splenectomy is a feasible extension of minimally invasive surgery in the hands of experienced surgeons. However, recognition of its limitations and ability to convert to the open procedure to assure safe excision is essential. PMID- 8340861 TI - Laparoscopic nephrectomy in the first year of life. AB - A child was found antenatally to have a cystic right kidney on maternal ultrasound. This was evaluated in the immediate postnatal period with imaging studies and confirmed to be a multicystic, dysplastic kidney. Expectant management was followed; however, the kidney was found to be unchanged in size on a 6-month ultrasound and the parents elected surgical removal rather than continued medical surveillance. A nephrectomy was performed using laparoscopic techniques rather than standard open surgery. Operating time was less than 1 hour. The patient's recovery was unremarkable. PMID- 8340862 TI - Abnormal aorta and iliac arteries in children with urogenital abnormalities. AB - Retroiliac ureters have been found in association with a variety of urogenital abnormalities but the iliac artery usually retains a retroperitoneal position. We report 7 children with various urogenital abnormalities (cloacal malformation 4, bladder agenesis 1, urogenital sinus 1, neuropathic bladder 1) in whom the lower aorta and iliac arteries were so distorted as to pose a significant operative hazard. In all cases the distal aorta and/or iliac arteries lay within the peritoneal cavity, often anterior to the bladder. In 3 cases the aorta was fixed by a short ligament to the umbilicus, and in 3 patients one of the iliac arteries ran across the pelvis behind the pubic bones before entering the leg. In one patient an anomalous iliac artery was inadvertently divided during reconstruction of a cloaca; when recognized, the vessel was rejoined. Recognition of an association between urogenital or cloacal malformations and a major vascular anomaly is of great importance to reconstructive surgeons who, if not forewarned, could unintentionally compromise the arterial supply to one or both lower limbs. PMID- 8340863 TI - The mild end of the clinical spectrum of posterior urethral valves. AB - Posterior urethral valves have a broad clinical spectrum. In this series of 87 patients, 36 had mild valvular obstruction, the most common clinical variety. Boys with mild valves had a greater frequency of diurnal and nocturnal enuresis, super-imposed infection, and a poor stream. The diagnosis was established by a very strict correlation of the radiological and endoscopic findings. Urodynamic studies, although performed in a limited number of patients, add validity to the diagnosis of mild valves. A classification based on the secondary anatomical changes and functional damage, which divides the valves in mild, moderate, and severe is recommended. Results of the endoscopic fulguration were excellent and without complications; 34 of 36 patients were improved or cured of their disturbing symptoms. PMID- 8340864 TI - University of Wisconsin preservation solution compared with Euro Collins preservation solution in pediatric liver transplantation. AB - Orthotopic liver transplantation has become the accepted treatment for end-stage liver disease in children. To evaluate the efficacy of the University of Wisconsin (UW) preservation solution in pediatric liver transplantation, a group of 34 livers preserved with UW solution was compared in a nonrandomized fashion with a historical control group of 34 livers preserved with Euro Collins (EC) solution. Primary graft nonfunction did not occur in either group. Both groups were similar with respect to age, sex, weight, diagnosis, severity of the recipient's condition, donor condition at harvest, donor/recipient blood type match, and immunosuppressive management. The UW group had a significantly higher bilirubin, AST, ALT, and GGT during the first week after transplantation when compared with the EC group but no significant differences were noted after the ninth post-transplant day. No differences were noted when the groups were compared as to surgery time (9.1 v 8.4 hours), blood volumes replaced (1.8 v 2.0), number of ICU days (5.0 v 6.5), total number of infections per graft (1.0 v 0.8), total hospital days (31 v 30), and hospital cost ($134,000 v $126,000). The total preservation time was improved from 7 hours (range, 3.2 to 9.9) in the EC group to 13.9 hours (range, 6.9 to 22.3) in the UW group (P < .001). UW solution allows a significant increase in cold ischemic time in liver transplantation when compared with EC. This increase in preservation time resulted in no detrimental effect when compared with EC and potentially led to milder episodes of rejection in the postoperative period. PMID- 8340865 TI - Pancreatic anatomy in children: emphasis on its importance to pancreatectomy. AB - The literature is riddled with misconceptions concerning the landmarks and the actual amount of pancreatic tissue resected in "subtotal" 60% to 90% pancreatectomies. In order to clarify the surgical anatomy of the pancreas, 13 autopsy specimens from children aged 2 days to 15 years were carefully examined. Pancreata were serially removed from the in situ position in four sections and weighed. Section 1 included pancreatic tissue from the tail to the left of the superior mesenteric vessels (SMV); section 2 included all tissue from the tail to the right of the SMV; section 3 contained tissue up to the left of the pancreaticoduodenal vessels in the head of the pancreas; and section 4 included the remainder of the pancreatic head within the duodenal sweep and the uncinate process. Results showed that section 1 weighed 47.5% +/- 9.7% (mean +/- SD) of the total pancreatic weight with a wide range of 32.3% to 67.3%; section 2 weighed 53.5% +/- 9.0% (range, 38.7% to 72.2%); section 3 weighed 69.1% +/- 15.6% (range, 43.5% to 95.8%); and section 4 weighed 31.6% +/- 14.6% (range, 4.2% to 56.5%). As noted, pancreatic anatomy was extremely variable in relation to the percent of tissue to either side of the SMV and the proportion of tissue contained within the uncinate process. Resections historically reported to result in a "75%" pancreatectomy (section 2) were demonstrated to contain a mean of only 53.5% +/- 9.0% of the pancreas. Less tissue than expected would be resected by using the SMV as landmarks for a 75% resection. The wide variation in anatomy also has important clinical implications in performing "subtotal" pancreatectomies in infants with nesidioblastosis in whom the amount of tissue resected is critical to the patient's postoperative clinical course. This study demonstrates that a subtotal pancreatectomy should not be based upon the presumed relation of the pancreatic substance to the SMV. The entire gland including the uncinate process should be visualized at operation in order that a proper pancreatectomy is performed. PMID- 8340866 TI - Surgical treatment of intractable cholestasis associated with total parenteral nutrition in premature infants. AB - We report surgical reversal of intractable total parenteral nutrition (TPN) associated cholestasis refractory to conservative treatment in 9 premature infants. Indications for TPN were poorly tolerated enteral feedings in all patients. Five patients had undergone gastrointestinal operations; in addition, 7 of the 9 patients had had bacterial sepsis. The median duration of TPN was 28 days (range, 20 to 50 days). The median duration of preoperative full enteral nutrition after weaning from TPN was 34 days (range, 16 to 95 days). All patients had progressive conjugated hyperbilirubinemia, no excretion of Tc-labeled HIDA to the biliary tree and duodenum, and markedly elevated liver enzyme values. Intraoperative cholangiography showed normal biliary anatomy in all cases; in addition, 2 patients had gallbladder stones. Bile was hyperviscous in all patients and contained biliary sludge in 4. The biliary tree was irrigated and the liver biopsied in all patients. The gallbladder was removed from 2 patients who had stones in the gallbladder. Liver histology was consistent with TPN associated cholestasis in all cases, and in addition, 4 cases showed significant destruction of intrahepatic bile ducts. One patient died 2 weeks postoperatively from intracerebral hemorrhage. Jaundice completely resolved in other patients within 2 weeks. HIDA-biligraphy performed 1 to 2 months postoperatively showed normal excretion of the radioactive marker to the biliary tree and duodenum in all cases. The functional abnormality in bile excretion and bile duct motility in TPN-associated cholestasis may be reversed by irrigation of the biliary tree. Surgical intervention should be considered when cholestasis is progressive and refractory to medical management. PMID- 8340867 TI - Problems with intestinal lengthening. AB - The surgical problems encountered in treating three infants with short-bowel syndrome are reported. The two survivors demonstrate many of the problems associated with the very short-bowel syndrome and both are dependent on parenteral nutrition despite undergoing intestinal lengthening. PMID- 8340868 TI - Epigastric heteropagus. AB - Incomplete parasitic twinning with the parasite attached at the host's epigastrium is extremely rare. We report a case of epigastric parasitic twinning where the parasite with a well-developed pelvis and lower limbs had accessory pelvic organs and was attached to the host above an omphalocele. The parasite was excised and the omphalocele managed conservatively by mercurochrome application. A review of the four previously reported cases is presented along with a discussion of the possible etiopathogenesis and nomenclature of this condition. PMID- 8340869 TI - An unusual form of caudal duplication (dipygus). AB - An unusual case of caudal duplication is presented in which the infant had an extra lower limb with 14 digits attached to an accessory parasitic pelvis situated in the midline subpubic area. Duplication of the external genitalia was also present. Successful excision of the accessory limb and reconstruction of the genitalia was performed in the neonatal period. PMID- 8340870 TI - Reconstruction of hypoplastic aortic arch and coarctation in a 720-gram premature infant. AB - The case of a 720-g infant born at 29 weeks of gestation who underwent successful surgical correction of a hypoplastic aortic arch and aortic coarctation is presented. The infant was initially brought to surgery with an echocardiographic diagnosis of patent ductus arteriosus with left to right shunt unresponsive to indomethacin therapy. The correct diagnosis of hypoplastic aortic arch and severe coarctation with ductal dependent blood flow to the lower body was made intraoperatively. This case illustrates the danger of limited diagnostic testing in premature infants assumed to have isolated patent ductus arteriosus, and also that these small infants can undergo successful surgical repair of complex aortic arch lesions. PMID- 8340871 TI - Primary occlusion of the iliac and femoral artery in two newborn infants: efficacy of medical treatment. AB - Arterial occlusion not associated with umbilical artery catheterization is a rare condition in the newborn period. Two neonates with femoral and iliac artery occlusion in the first days of life are presented. While almost all the cases described in the literature underwent surgical treatment, these two infants received only pharmacological treatment with good results. Although angiography remains the examination of choice for the diagnosis, noninvasive angiologic evaluations such as oscillometry and Doppler flow examination have been used for both diagnosis and follow-up. The etiology in these two cases remains unknown. The results obtained with these two neonates suggest that with prompt recognition of this disorder and an aggressive medical treatment, a complete recovery could be achieved. PMID- 8340872 TI - Osteoid osteoma of the rib: a case report. AB - A case of a 6-year-old boy with a painful dorsal scoliosis secondary to an osteoid osteoma in a rib is described. Surgical excision was performed and the scoliosis decreased. Such cases are very rare. PMID- 8340873 TI - Infantile hemangiopericytoma: a rare cause of a soft tissue mass. AB - A case of infantile hemangiopericytoma in a neonate is presented. The clinicopathologic characteristics of this tumor are described. This tumor is often confused for other more aggressive malignant tumors and, thus, is likely under-reported and overtreated. These tumors exhibit features suggestive of malignancy such as increased mitotic activity, nuclear pleomorphism, and increased cellularity, yet are clinically unpredictable. A conservative surgical approach is advocated. PMID- 8340874 TI - Rapid decompression of chronic hydrocephalus resulting in bilateral extradural hematomas; a general surgical complication. PMID- 8340875 TI - Opening of both vasa into a mullerian duct cyst. PMID- 8340876 TI - Nitrofen-induced diaphragmatic hernias in rats: an animal model. PMID- 8340877 TI - Pediatric community needs. PMID- 8340878 TI - The development of a comprehensive bereavement program to assist families experiencing pediatric loss. AB - One of the most difficult situations encountered by pediatric nurses is dealing with families experiencing the death of a child. This article describes the development of the H.O.P.E.S. Program (Healing of Parents Experiencing Sorrow), a comprehensive bereavement program designed to assist families who have experienced pediatric loss. This program has been well-received by both families and staff and has enabled staff to interact more confidently with families at a very difficult time in their lives. PMID- 8340879 TI - The effect of the sight of blood and use of decorative adhesive bandages on pain intensity ratings by preschool children. AB - A total of 70 children between the ages of 3 and 6 years participated in two studies that tested the effect of (a) the sight of blood and (b) the application of a decorated adhesive bandage on pain intensity ratings following a fingerstick. In both studies, children were randomly assigned to one of four groups. These groups allowed for the combinations of testing blood or no blood and the application of a decorated adhesive bandage or plain adhesive bandage. The Oucher (Beyer, 1984) and the Poker Chip Tool (Hester, 1979) were used as self report measures of pain intensity at the time of the fingerstick and immediately after the application of the adhesive bandage. The pilot study recruited 20 children from two day care centers and subjected them to sham fingersticks. Results indicated that there were no differences across the groups in pain intensity ratings. However, there was a trend for the sight of blood to increase the child's pain intensity rating. Age was a significant covariate across all groups, with younger children reporting higher levels of pain intensity. The second study took place in a pediatric test center of a metropolitan children's hospital. Fifty outpatient children who were receiving fingersticks for preoperative or diagnostic testing were enrolled. Results indicated that there were no differences across groups, and age was only significant on the Poker Chip Tool. These results suggest that simple interventions and distractions are not sufficient to decrease perceived pain intensity ratings in young children. PMID- 8340880 TI - Prevalence study of substance abuse in a midwestern city. AB - Illicit substance abuse among pregnant women has been documented in many large metropolitan areas. However, there has been limited documentation in smaller, more traditional cities of America. The urine of 105 viable newborns delivered within a 30-day period was tested for illicit drugs in a blind study. Positive results were obtained in 9.5% of the subjects. The following demographic data were compiled about the subjects: (a) type of identified substance; (b) age of mother; (c) timing of mother's entry into prenatal care; (d) maternal complications; (e) newborn complications; (f) newborn gestational age; and (g) mother's economic status. PMID- 8340881 TI - Survey of nursing research programs in children's hospitals. AB - Available published literature describing successfully implemented research programs is relatively limited, particularly within children's hospitals. In order to determine the status of research program development within children's hospitals, a mailed survey was sent to 108 free-standing children's hospitals in the United States and Canada. The questionnaire was comprised of questions pertaining to five general sections: (a) institutional demographics; (b) organizational structure for research; (c) research activities; (d) relationship to other agency research; and (e) demographic characteristics of the individual completing the survey. Findings indicated that nursing research within children's hospitals is in an early development state, but that it is recognized as a necessary and credible component of nursing. Differences were noted between the groups of hospitals with the most research activity and those with no research activity. Hospitals were in various stages of research development, a sequential process characterized by a sequential pattern comprised of two phases. PMID- 8340882 TI - Acute rheumatic fever revisited. AB - Acute rheumatic fever, often believed to have been eradicated, has shown an increase in prevalence and virulence within the past few years. This article discusses current epidemiology, assessment findings, medical treatment, and nursing interventions for the child with rheumatic fever. Principles of prevention and implications for health teaching are included. PMID- 8340883 TI - Sources of Family Annoyance (SOFA): development, reliability, and validity. AB - The Sources of Family Annoyance (SOFA) is a brief questionnaire intended to measure chronic stressors experienced by fathers and mothers in the home. Two scales, Household Negatives and Child Negatives, were derived from factor analysis. Experiment 1 demonstrated that the instrument discriminated a group of parents of psychiatric clinic-referred children from nonreferred parents. Experiment 2 demonstrated that the instrument discriminated mothers who were receiving public assistance from mothers in a community sample. Results suggest that the SOFA is a reliable and valid brief parent stress assessment instrument that may be useful in family-based interventions to reduce stress and improve the course of pediatric illness. PMID- 8340884 TI - The emerging need for a SIDS support group for family child care providers in Minnesota. AB - In Minnesota, 37% of all deaths due to Sudden Infant Death Syndrome (SIDS) in 1989 occurred in a family child care home. An ongoing monthly support group was developed for child care providers who experienced a SIDS-related death in their homes. This was developed in response to a desire to have a support group specifically for providers and separate from parent support groups. Evaluation by group participants indicated that such a group was effective in helping them work through the grief process. PMID- 8340885 TI - Homeless children and their families, Part II: Federal programs and alternative health care delivery systems. PMID- 8340887 TI - Creative approaches to promoting parent-infant bonding. PMID- 8340886 TI - Glucometers: accuracy and precision, Part II. Selection of a blood glucose monitor for standard hospital use. PMID- 8340888 TI - A trip to the Australian Outback. PMID- 8340889 TI - HIV infection in 567 active pulmonary tuberculosis patients in Brazil. AB - We studied 567 patients with active pulmonary tuberculosis (APT) in Rio de Janeiro, Brazil, by using a standardized questionnaire and by testing blood for HIV antibodies. The rate of HIV infection was 3.9% in 1987, 4.8% in 1988, and 5.2% in 1989, and did not differ by sex. It was highest (7.4%) in the 15- to 39 year age group. There was no difference between patients infected and not infected by HIV with regard to education, income, housing, or employment. Among all patients with definite HIV risk behavior, the HIV infection rate was 23.3%, rising to 31.2% among homo/bisexual men and 36.4% among intravenous drug users, and the rate was 6.5% for blood-transfusion recipients. Among patients who denied risk behavior, the rate was 1.2%. Generalized lymphadenopathy and oral candidiasis occurred with greater frequency among HIV-infected patients (p < 0.0001). Applying the World Health Organization 1985 clinical criteria and revised case definition for AIDS, we found, respectively, sensitivities of 34% and 76.9% and specificities of 31% and 26.3%; in the Rio de Janeiro environment, these clinical criteria without HIV serology should not be adopted for tuberculosis patients. For chest radiographs, a significant association was found between HIV infection and the occurrence of atypical images (p = 0.0001), and hilar and/or mediastinal adenopathy (p = 0.0002) and absence of cavities (p = 0.0003). A PPD (purified protein derivative) skin test induration of < 5 mm was identified in 53% of the HIV-positive cases and in 31.3% of the HIV-negative cases. Only 11.5% of HIV-infected APT patients met the Centers for Disease Control 1987 AIDS criteria. PMID- 8340890 TI - Response of human immunodeficiency virus-infected adults to measles-rubella vaccination. AB - Measles-mumps-rubella vaccine (MMR) is recommended for human immunodeficiency virus-infected (HIV+) adults. Data concerning MMR vaccination of HIV+ patients are limited to children. We evaluated 39 HIV+ (97% with > 200 CD4+ lymphocytes) and 17 non-HIV+ control adults receiving measles-rubella vaccine (MR). Clinical adverse events did not differ between groups. Prevaccination, three HIV+ and two control vaccinees were measles seronegative; no HIV+ and one control vaccinee seroconverted. No initially measles-seropositive vaccinee had a significant antibody elevation. Four HIV+ and three control vaccinees were rubella seronegative prevaccination; three HIV+ and two control vaccinees seroconverted. Among those initially rubella seropositive, two HIV+ and one control vaccinee had significant antibody elevations. There were no significant percentage CD4+ or CD8+ lymphocyte changes between groups. Three HIV+ vaccinees were p24 antigen positive pre- and postvaccination. Although MR vaccination appears safe in HIV+ adults, questions remain about the response of measles and rubella antibody negative HIV+ adults and those with < 200 CD4+ lymphocytes. PMID- 8340891 TI - Altered production of PGE2, IL-1 beta and TNF-alpha by peripheral blood monocytes from HIV-positive individuals at early stages of HIV infection. AB - We analyzed the in vitro synthesis and release of PGE2, IL-1 beta, and TNF-alpha by peripheral blood monocytes from HIV-infected injection drug users at the early clinical stages of HIV infection. We investigated whether there is a concomitant altered production of PGE2 and proinflammatory cytokines by HIV-positive monocytes. We also evaluated T-cell subsets and lymphocyte transformation response to pokeweed mitogen (PWM) in HIV-positive patients and healthy controls. PGE2 and IL-1 beta levels in supernatants from monocyte cultures were determined by radioimmunoassay (RIA), and TNF-alpha by enzyme immunoassay (EIA). Monocytes from asymptomatic HIV-positive individuals produced spontaneous and significantly increased quantities of PGE2, IL-1 beta, and TNF-alpha. Concomitant increased production of PGE2 and IL-1 beta by monocytes from HIV-positive asymptomatic patients was significantly associated with low CD4+ T-cell numbers (< 500 cells/mm3). We also found a strong association between spontaneous and concomitantly increased production of PGE2 and cytokines by monocytes from asymptomatic HIV-positive individuals and a low lymphocyte transformation response to PWM. Further studies are necessary to establish whether this altered production of PGE2 and proinflammatory cytokines by monocytes from HIV-positive individuals might play a role in the mechanisms involved in the progressive impairment of cell-mediated immunity in HIV infection. PMID- 8340892 TI - Prevalence of intestinal protozoans in French patients infected with HIV. AB - To assess the prevalence of intestinal protozoans in French HIV-infected patients, stool samples, duodenojejunal biopsies, and/or colorectal biopsies from 81 patients were studied for parasites, viruses, and bacteria. Pathogens were found in 70.6% of AIDS patients with diarrhea or malabsorption. The respective prevalence of protozoa in AIDS patients with diarrhea was Cryptosporidium sp.: 37.3%, Blastocystis hominis: 13.7%, Giardia intestinalis: 5.8%, Isospora belli: 2%, Enterocytozoon bieneusi: 2%. Microsporidia were noted in one patient with severe malabsorption but no diarrhea. Other pathogens included cytomegalovirus in 27.4% and Mycobacterium avium in 5.8%. Patients with identified pathogens were more immunosuppressed and more severely malnourished than those with unexplained diarrhea. Multiple pathogens were found in 13 of 81 patients (16%). Twenty-six of 66 identified pathogens (40%) were diagnosed only on biopsy specimens. Chronic diarrhea in HIV patients could be explained in the vast majority by appropriate gastrointestinal investigations. Cryptosporidia played a major role, while microsporidia appeared to be less common. PMID- 8340893 TI - The initial detection of human immunodeficiency virus 1 and its subsequent spread in prostitutes in Tamil Nadu, India. AB - To determine the prevalence of HIV-1 antibody and risk factors associated with a positive test in a heterosexually promiscuous female population, we initially screened 412 prostitutes in remand homes in three cites and three towns in Tamil Nadu state (southern India) and then tested all new entrants to one home in Vellore from 1986 to 1990. The proportion of women infected (10 of 102) from the port city of Madras was greater than from all other cities or towns combined (four of 310, p = 0.0002). The only significant risk factor for development of HIV-1 antibody was exposure to foreigners (odds ratio: 7.71; 95% confidence interval 4.2-11.2; p = 0.0004), after correcting for the influence of city. In Vellore the prevalence of HIV-1 antibody increased from 1.8% in 1986 to 28.6% in 1990, with a doubling time of 0.95 years. We hypothesize that HIV-1 infection has been introduced into India relatively recently into the heterosexually promiscuous population, where there has been some spread. Preventive measures should be urgently directed toward this population to prevent spread in the general population. PMID- 8340894 TI - Urban-nonurban distribution of HIV infection in childbearing women in the United States. AB - Women account for an increasing proportion of AIDS cases in the United States, and the number reported from small cities and rural areas is growing. To better describe the geographic characteristics of the human immunodeficiency virus (HIV) epidemic in women, we analyzed data for more than 1.6 million newborn specimens tested for maternal antibody to HIV-1 in 35 states in 1989. To provide comparable geographic units for analysis, seroprevalence rates were calculated for state designated health districts, which are groups of counties defined for the planning and delivery of health services. Health districts with > or = 75% of the population residing in urban areas as defined by the 1990 census were considered urban. Prevalence of HIV infection ranged from 0 to 12.2 per 1,000, with the highest rates found in urban health districts, primarily those on the East coast; however, high rates were also found in some nonurban districts, particularly in the South. Rates among black women were three to 35 times higher than in white women in nine states, regardless of urbanicity. These findings should be used to focus prevention activities and direct health care planners to urban and rural areas in need of HIV-related services for women. PMID- 8340895 TI - Prevention of heterosexual transmission of human immunodeficiency virus through couple counseling. AB - In the absence of an effective vaccine, behavior change remains the most effective means to prevent the spread of HIV. We examined behavior change over time and rates of HIV seroconversion in a cohort of HIV individuals and their heterosexual partners recruited since 1985. Participants were recruited from various HIV counseling and testing sources throughout California and were usually interviewed and tested in their own homes. Couple counseling and risk assessments were conducted at average intervals of six months. Data from 144 couples who were discordant for HIV serostatus are reported. Of the index cases, 78% were men. Most male index cases were bisexuals, and most female index cases were infected through heterosexual intercourse with a previous sexual partner. The mean duration of the relationship for the couple at intake was 5.6 years. Both condom use and sexual abstinence increased over time (p < 0.001 for both), and most behavior change occurred between intake and first follow-up visit. We observed no seroconversion after 193 couple-years of follow-up. Couple counseling in combination with social support appears to be an effective means to promote and sustain behavior change among HIV-infected individuals and their heterosexual partners. PMID- 8340896 TI - Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: an 18-month prospective follow-up. AB - Our objective was to determine the prevalence and incidence of human immunodeficiency virus (HIV) infection and related risk behaviors among opiate abusing intravenous drug users (IVDUs) either in or out of methadone treatment. The subjects, 152 in-treatment and 103 out-of-treatment intravenous opiate users, were followed prospectively for 18 months. Behavioral and serologic assessments were made at 6-month intervals, with complete information available on 89% of the sample. Subjects were recruited from a single methadone maintenance program and the surrounding neighborhood in north-central Philadelphia. At baseline, the HIV seroprevalence rate for the total sample was 12%: 10% for the methadone maintained group and 16% for the out-of-treatment group. Out-of-treatment subjects were injecting drugs, sharing needles, visiting shooting galleries, and practicing unsafe sex at significantly higher rates than in-treatment subjects. Follow-up of HIV-negative subjects over the next 18 months showed conversion rates of 3.5% for those who remained in methadone maintenance versus 22% for those who remained out of treatment. The sixfold difference in rate of seroconversion between the two groups suggests that although rapid transmission of HIV still occurs, opiate-abusing IVDUs who enter methadone treatment are significantly less likely to become infected. In contrast, those opiate addicts who do not enter treatment are at significantly higher risk of contracting and spreading the disease. Implications for developing additional risk interventions for out-of-treatment IVDUs are discussed. PMID- 8340897 TI - Laboratory-based reporting of AIDS. AB - To improve the speed and completeness of AIDS reporting, the Philadelphia Board of Health adopted regulations requiring medical laboratories to report directly to the Department of Public Health all results indicative of AIDS-defining diagnoses. Reports were used to focus active AIDS surveillance on physicians who had requested laboratory reports whose results were likely to have diagnosed AIDS recently. One year after implementation, laboratories provided the first lead to 20% of all AIDS reports. Reports originating with laboratories reach our data base sooner after diagnosis and ascertain a slightly higher proportion of women than do other reports. Laboratory-based reporting offers a practical way to focus the limited resources available for active surveillance on health providers likely to have an AIDS diagnosis to report. PMID- 8340898 TI - Human T lymphotropic virus type I/II in Lake Lindu Valley, Central Sulawesi, Indonesia. PMID- 8340899 TI - Attitudes to euthanasia and assisted suicide in a group of homosexual men with advanced HIV disease. PMID- 8340900 TI - Cellular immune response to SIVmac and HIV-2 in macaques: model for the human HIV 1 infection. AB - SIV and HIV-2 infection of macaques has become a widely used model to study human HIV infection because the pathogenicity of, as well as the immune responses to, the viruses can be examined conveniently. In particular, the cellular immune responses to SIV or HIV-2 have been investigated thoroughly. This review summarizes the knowledge about helper and cytotoxic T-cell immunity in macaques, and it discusses the relevance and applications of this primate animal model for AIDS research. PMID- 8340901 TI - Serum inhibitors precede the development of SAIDS. AB - Rhesus macaque monkeys infected with the simian immunodeficiency virus develop a syndrome mimicking AIDS in humans. We have demonstrated previously that sera from individuals infected with human immunodeficiency virus type 1 inhibit the proliferation of lymphocytes from healthy noninfected subjects and that this phenomenon is associated with the development of clinical AIDS. We have also shown that sera from monkeys infected with SIV also have such inhibitors. In this body of work, we attempted to document the onset of these inhibitors in relation to the time of SIV infection. Twenty rhesus macaques were injected with one of two tissue strains of SIV or media. Blood was drawn on a set schedule and the serum samples frozen at -70 degrees C. The animals were monitored and observed for up to 42 weeks. All test animals were autopsied. Sera from all the draws were assayed against the same populations of human peripheral blood mononuclear cells in the same experiment using suboptimal amounts of phytohemagglutinin (PHA). Sera from those animals that subsequently developed SAIDS were more likely to demonstrate serum inhibition. This inhibition could be seen as early as 8-10 weeks after infection. By week 14, the assay could differentiate animals into SAIDS or healthy groups with a sensitivity of 67% and a specificity of 89%. PMID- 8340902 TI - Tots and teens: similarities in behavior and interventions for pediatric and psychiatric nurses. AB - The separation-individuation process is played out in similar ways by toddlers and teenagers. Child and adolescent psychiatric nurses may have a better appreciation of the subtleties and complexities in dealing with behaviors of these patients with a comparison of the two groups. This paper discusses similarities in behaviors of toddlers and teens and presents theory-based guidelines for interventions with clients in these age groups. PMID- 8340903 TI - Sexually abused boys: awareness, assessment, and intervention. AB - The prevalence and consequences of the sexual victimization of young boys is tragically underestimated. The author provides data on the incidence of sexual abuse in boys and girls, ages 3-10, in an inpatient psychiatric children's unit. A retrospective chart review is presented including variables of coexisting maltreatment and symptomatology. Commonly found nursing diagnoses are identified with appropriate nursing interventions. Assessing a sexually abused boy, developing a comprehensive nursing care plan, and intervening effectively in assisting a child to assimilate and cope with his abuse experience are discussed in depth. PMID- 8340904 TI - A letter to Hillary Rodham Clinton. PMID- 8340905 TI - Attending nurses. PMID- 8340906 TI - Growth and development of the brain. PMID- 8340908 TI - The sicker get healthier and the healthier get sicker; eventually the twain shall meet. PMID- 8340907 TI - The first 100 days and hopes for children. PMID- 8340909 TI - Excursions in drug discovery. PMID- 8340910 TI - (S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1- carbaldehyde: a new class of orally active 5-HT1A-receptor agonists. AB - The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S (-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+) 6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n propylamino)tetrahydronaphthalene (8-OH-DPAT). In contrast to 8-OH-DPAT, the enantiomers of compound 6 were found to have good oral availability. PMID- 8340911 TI - Synthesis and antitumor properties of an anthraquinone bisubstituted by the copper chelating peptide Gly-Gly-L-His. AB - A new molecule 4 [(GGH-DAE)2DHQ] associating the 1,4,5,8 tetrahydroxyanthraquinone ring (DHQ) of the antitumor drug mitoxantrone (2), two diaminoethylene chains (DAE), and the metal-chelating peptide Gly-Gly-His (GGH) has been synthesized. Such a molecule presents characteristics able to induce antitumor activity: compound 4 intercalates into DNA as measured by delta Tm, fluorescence quenching, and viscometry; ESR studies demonstrate that several types of Cu complexes are formed depending on pH; and the production of free radicals, as evidenced by spin-trapping, is enhanced by 4. In vitro, in leukemia cells L1210 and mammary cells MCF7, 4 is slightly less cytostatic than mitoxantrone, but substantially less toxic. In vivo, in leukemia P388 on mice, a T/C value of 230 is obtained at 25 mg/kg, higher than the one of mitoxantrone, which is toxic at the same dose. PMID- 8340912 TI - Reductive activation of potential antitumor mitosene compounds. AB - The reductive activation of mitosene compounds was studied with cyclic voltammetry and HPLC analysis. Reduction of mitosenes, possessing good leaving groups at C-1 and C-10, was shown to result in loss of these groups at pH 7.0 and pH 6.0. The loss of leaving groups from mitosenes occurred faster at lower pH. Mitosenes without good leaving groups were found to be stable upon reduction. In the presence of acetoxy groups at C-1 and C-10, the C-10 site is the most reactive site upon reductive activation. This is opposite to the case of mitomycin C, where the C-1 site is the first to react upon reduction. At pH 6.0 without reduction, acid degradation also caused the loss of leaving groups of mitosenes, although at a very slow rate. In contrast to reductive activation, upon acid degradation of a diacetoxymitosene the C-1 group appeared to be lost faster. Electrochemical as well as dithionite reduction of a bifunctional (diacetoxy) mitosene compound in the presence of calf thymus DNA at pH 5.5 resulted in the formation of DNA interstrand cross-links. Depending on activation method, this diacetoxymitosene was at least as efficient in DNA cross-linking as mitomycin C under comparable conditions. PMID- 8340913 TI - N-phosphoryl derivatives of bisantrene. Antitumor prodrugs with enhanced solubility and reduced potential for toxicity. AB - The selective phosphorylation of bisantrene (1) affords bis(phosphonoguanidinic acid) 6, a prodrug with enhanced aqueous solubility (as sodium salt 7) at physiological pH. Unlike 1, in a rat tail vein model, no precipitation was observed when bis(phosphonoguanidinic acid) 6 was injected. While in rats 6 hydrolyzed to monophosphonoguanidinic acid 9 with a half-life of ca. 12 min., complete hydrolysis to bisantrene required several hours. The corresponding monophosphonoguanidinic acid 9 was synthesized from bisantrene and also showed good solubility and antitumor activity. While the antitumor activities of 6 in mice were comparable to bisantrene against B-16 melanoma and P-388 and L-1210 leukemias, it was inactive in vitro vs several tumor cell types. Thus, its activity in vivo resulted from its ability to serve as a prodrug for bisantrene. PMID- 8340914 TI - Syntheses of 5'-substituted analogues of carbocyclic 3-deazaadenosine as potential antivirals. AB - Various 5'-substituted derivatives (2, 3, 6a, 6b, 9a, 9b, 12, 13b, and 15) of carbocyclic 3-deazaadenosine (3-deaza CAdo, 1) were prepared from 3-deaza CAdo (1) and evaluated as antiviral agents against a number of viruses, including HIV 1. Several of the compounds had moderate to good antiviral activity against vaccinia (VV) and vesicular stomatitis (VSV) viruses; however, the antiviral activity of the analogues did not exceed that of the parent compound. No anti-HIV activity was detected. PMID- 8340915 TI - Synthesis and structure-activity relationships of phenyl-substituted benzylamine antimycotics: a novel benzylbenzylamine antifungal agent for systemic treatment. AB - Derivatives of the benzylamine antimycotics with an extra phenyl ring incorporated in the side chain have been prepared and their antifungal activity evaluated. The potency is strongly dependent on the distance between the two phenyl groups and the type of spacer. Linking the aryl rings with a quaternary carbon atom resulted in the identification of highly active compounds 7f and 12a, having a novel 4-benzylbenzylamine side chain. Compound 7f and its 7 benzo[b]thienyl analogue 12a show significantly enhanced efficacy, in particular against Candida albicans, and are among the most potent allyl/benzylamine antimycotics identified so far. Extended investigations with the benzylbenzylamine derivative 7f revealed that, in addition to the enhanced antimycotic profile, the compound is the first representative of the benzylamine antimycotics suitable for systemic treatment. PMID- 8340916 TI - 2,2-Dialkylnaphthalen-1-ones as new potassium channel activators. AB - A new series of 2,2-dialkylnaphthalen-1-one potassium channel activators has been prepared, and their in vitro relaxant activities in isolated rat portal vein and guinea pig tracheal spirals as well as their oral antihypertensive effect in spontaneously hypertensive rats have been evaluated. The group of 1,2-dihydro-4 (1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethylnaphthalen -1- ones with an electron withdrawing substituent at the 6-position contain the most active compounds and 1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonaphtha lene-6- carbonitrile, 17f (UR-8225), has been selected for further pharmacological development. PMID- 8340917 TI - Sulfonylmethanesulfonamide inhibitors of carbonic anhydrase. AB - A series of sulfonylmethanesulfonamide derivatives is described, which are inhibitors of carbonic anhydrase (CA). The most potent of these is the racemic fluoro sulfone 9, which inhibits carbon dioxide hydration catalyzed by human CA II (CA-II) with an IC50 of 3 nM. Binding competition studies versus dansylamide indicate that the enantiomers of 9 have different affinities for CA-II, with equilibrium dissociation constants of 3.6 and 0.6 nM. QSAR analysis suggests that the key factors involved in achieving high affinity in this series are sulfonamide acidity, hydrophobicity, and minimization of steric demands at the carbon atom adjacent to the sulfonamide group. PMID- 8340918 TI - Multiple copy simultaneous search and construction of ligands in binding sites: application to inhibitors of HIV-1 aspartic proteinase. AB - Rational ligand design is a complex problem that can be divided into three parts: the search for optimal positions and orientations of functional groups in the binding site, the connection of such positions to form candidate ligands, and the estimation of their binding constants. Approaches for addressing the first two parts of the problem are described in the present work. They are applied to the construction of peptide ligands in the binding site of the human immunodeficiency virus 1 (HIV-1) proteinase. The primary objective is to test the method by comparison of the results with the MVT-101 complex structure for which coordinates are available; the results obtained with the liganded and unliganded proteinase structure are used to examine the utility of the latter for binding studies. A secondary objective is to show how to find new inhibitor candidates. The multiple copy simultaneous search (MCSS) method is utilized to search for optimal positions and orientations of a set of functional groups. For peptide ligands, functional groups corresponding to the protein main chain (N methylacetamide) and to protein side chains (e.g., methanol, ethyl guanidinium) are used. The resulting N-methylacetamide minima are connected to form hexapeptide main chains with a simple pseudoenergy function that permits a complete search of all possible ways of connecting the minima. Side chains are added to the main-chain candidates by application of the same pseudoenergy function to the appropriate functional group minima. A set of 15 hexapeptides with the sequence of MVT-101 is then minimized by a Monte Carlo scheme, which allows for escape from local minima. Comparison of the MCSS results with the structure of MVT-101 in the HIV-1 binding site showed that all of its functional group positions correspond (within 2.4 A) to some (usually more than one) MCSS minima. There were also many other low-energy MCSS minima which do not appear in any known inhibitors, e.g., methyl ammonium minima in the neighborhood of the catalytic aspartates. Among the 15 lowest minima are seven hexapeptides with the same main-chain orientation as the one found by X-ray crystallography for the inhibitor MVT-101 in the binding site and eight with the main chain oriented in the opposite direction; the latter tend to be more stable. [Addendum: These results are in agreement with recent high-resolution crystallographic data provided after the study was completed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8340919 TI - 4-Amidinoindan-1-one 2'-amidinohydrazone: a new potent and selective inhibitor of S-Adenosylmethionine decarboxylase. AB - Two isomeric amidino-2-acetylpyridine amidinohydrazones, 11 and 12, and 4 amidinoindanone amidinohydrazone, 17, have been synthesized and tested for inhibition of S-adenosylmethionine decarboxylase (SAMDC) and diamine oxidase and for antiproliferative activity against T24 human bladder carcinoma cells. Compound 11 inhibited SAMDC with an IC50 of 10 nM and was 140- and > 500-fold more potent than methylglyoxal bis(guanylhydrazone) (MGBG) and 12, respectively. The difference in potency between 11 and 12 was interpreted with the help of molecular modeling and appeared to be associated with two different low-energy conformations of the compounds. Compound 17 which represents a conformationally constrained analogue of 11, was superior to the latter and MGBG with respect to selective inhibition of SAMDC and antiproliferative activity, and is of interest as a potential anticancer agent and a drug for the treatment of protozoal and Pneumocystis carinii infections. PMID- 8340920 TI - Synthesis and structure-activity relationships of nonpeptide, potent triazolone based angiotensin II receptor antagonists. AB - 2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4' - yl]methyl] 3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2 phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized. PMID- 8340921 TI - Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazolecarboxylic acids. AB - A series of 2-substituted-1-[(biphenyl-4-yl)methyl]-1H-benzimidazole-7- carboxylic acids was prepared from the key intermediate 3-amino-2-[[(biphenyl-4- yl)methyl]amino]benzoate (6a-c) in order to clarify the structure-activity relationships of various analogues of 2-butyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4 yl]methyl]-1H-ben zimidazole- 7-carboxylic acid (CV-11194), a potent and long acting angiotensin II (AII) receptor antagonist. The AII antagonistic activity of the benzimidazoles was investigated by in vitro assays, which included an AII receptor binding assay and AII-induced vasocontraction assay, as well as by in vivo assays such as an AII-induced pressor response in rats. Most of the benzimidazoles showed high affinity for the AII receptor (IC50 value, 10(-6)-10( 7) M) and inhibited the AII-induced pressor response at 1 or 3 mg/kg po, and the effects were more potent than those of CV-11194 and DuP 753. The structure activity relationship studies on the binding affinity and the inhibition of AII induced pressor response suggested that straight chains of a certain length (e.g., ethoxy groups, ethyl groups) were the best as substituents at the 2 position and that their steric factors, lipophilicity, and electronic effects affected the potency of the AII antagonistic action. Both a carboxyl group at the 7-position and a tetrazole ring at the 2'-position were particularly important for potent and orally active AII antagonistic activity and a long-acting hypotensive effect. The representative compound, 2-ethoxy-1-[[2'-(1H-tetrazol-5 yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylic acid (26b, CV-11974), inhibited the specific binding of [125I]AII to bovine adrenal cortical membrane with an IC50 value of 1.1 x 10(-7) M. The AII-induced contraction of rabbit aortic strips was antagonized by CV-11974 (IC50 value, 3.0 x 10(-10) M). Oral administration of CV-11974 to conscious normotensive rats at 1 mg/kg resulted in long-lasting inhibition of the AII-induced pressor response. CV-11974 at 0.1-1 mg/kg iv reduced blood pressure dose-dependently in spontaneously hypertensive rats. PMID- 8340922 TI - Synthesis and biological activity of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro- 3 propyl-1H-benz[e]indole-9-carboxamide: a potent and selective 5-HT1A receptor agonist with good oral availability. AB - The synthesis and biological activity of cis-(3aR)-(-)-2,3,3a,4,5,9b- hexahydro-3 propyl-1H-benz[e]indole-9-carboxamide ((-)-3a), U93385, is described. The cis racemate and its enantiomer as well as the corresponding trans enantiomers were also synthesized and evaluated. The synthesis of these analogs was achieved via either a four-step conversion of the 9-hydroxy precursor into 9-carboxamide or an alternative synthesis using the (R)-alpha-methylbenzyl group as the chiral auxiliary. The cis racemate (+/-)-3a, was found to be a selective and potent 5 HT1A receptor agonist with the activity residing in the cis-(3aR)-enantiomer, (-) 3a. The cis-(3aS)-enantiomer (+)-3a and trans-(3aR)-enantiomer (-)-3b displayed partial 5-HT1A agonist activity whereas the other trans-(3aS)-enantiomer (+)-3b showed no activity. The enantiomer (-)-3a was found to be selective in both in vitro and in vivo biochemical/behavioral assays. This compound potently reduced rectal temperature in mice, decreased the firing rate of rat midbrain serotonergic neurons, and suppressed rat brain 5-HT synthesis. This compound also reduced sympathetic nerve discharge and blood pressure in the anesthetized cat and showed activity in the forced swim assay in mice. It exhibited good oral activity in behavioral and biochemical assays and, in fact, had a 46% oral availability in the rat when comparing blood levels of parent drug after iv and po administration. This compound has demonstrated a potential for anxiolytic and antidepressant activity and is currently undergoing clinical evaluation. PMID- 8340923 TI - Synthesis and antitumor activity of 10-propargyl-10-deazaaminopterin. AB - Successive alkylation of dimethyl homoterephthalate with propargyl bromide and 2,4-diamino-6-(bromomethyl)pteridine followed by ester saponification at room temperature afforded 2,4-diamino-4-deoxy-10-carboxy-10-propargyl-10-deazapteroic acid. The 10-COOH was readily decarboxylated by heating in DMSO at a temperature of only 120 degrees C to yield the diamino-10-propargyl-10-deazapteroic acid intermediate. Coupling with diethyl L-glutamate and ester hydrolysis gave the title compound. The 10-propargyl analogue was about 5 times more potent than MTX as an inhibitor of growth in L1210 cells, but was only one-third as potent as an inhibitor of DHFR from L1210. The analogue was transported inward very effectively in L1210 cells showing a 10-fold advantage over MTX. At a dose of 36 mg/kg the 10-propargyl compound caused shrinkage of the E0771 solid murine mammary tumor to only 1% of untreated controls. PMID- 8340924 TI - 1-Carboranyl-3-(2-methylaziridino)-2-propanol. Synthesis, selective uptake by B 16 melanoma, and selective cytotoxicity toward cancer cells. AB - 1-Carboranyl-3-(2-methylaziridino)-2-propanol (MACB) was prepared from the reaction of 1-carboranyl-2,3-epoxypropane with metalated methylaziridines having copper [Cu(CN)Li2]1/2 or lead (PbBu3) as the metal. MACB exhibited relatively high growth inhibition toward some cancer cells, and selective uptake of MACB by B-16 melanoma was accomplished. PMID- 8340925 TI - Selective inhibition of mammalian lanosterol 14 alpha-demethylase: a possible strategy for cholesterol lowering. PMID- 8340926 TI - Hydroxyurea derivatives as hypoglycemic agents. PMID- 8340927 TI - Triggered exocytosis and endocytosis have different requirements for calcium and nucleotides in permeabilized bovine chromaffin cells. AB - The intracellular requirements for membrane recapture in permeabilized chromaffin cells were compared to the requirements for exocytosis from the same cells. In permeabilized bovine chromaffin cells, calcium-driven exocytosis also triggers, with a short delay, uptake of extracellular horseradish peroxidase (HRP). This internalized HRP remains compartmentalized within the cell and migrates to a low density band on a Percoll gradient which is distinct from the heavier chromaffin granules. The amount of horseradish peroxidase internalized is similar in intact and leaky cells and is approximately equivalent to the volumes secreted. Endocytosis in both preparations is blocked by botulinum toxin, operates in a collapsed membrane potential, and is inhibited by low temperature. In permeabilized cells, exocytosis and coupled endocytosis are activated by the same concentrations of Ca2+ and MgATP. Although secretion requires Ca2+ and MgATP, once exocytosis has occurred the subsequent endocytosis can proceed in the virtual absence of Ca2+ or MgATP, and is largely unaffected by a variety of nucleotide triphosphates (including nonhydrolyzable analogues), and cyclic nucleotides. These data suggest that endocytosis can proceed, once exocytosis has been triggered, under conditions that are quite different from those necessary to support exocytosis, and that the specific requirements for Ca2+ and MgATP in secretion are for the exocytotic limb of the secretory cycle rather than for the associated endocytotic pathway. PMID- 8340929 TI - Fatty acid transfer across the myocardial capillary wall. AB - Interstitial transudate of isolated isometrically working perfused rat hearts was analyzed to investigate fatty acid (FA) release and transfer across the capillary wall. Unsaturated FA were released under certain conditions. Lowering medium FA (16:0) with constant or varying FA/A-ratio (A: albumin) decreased interstitial FA concentration down to 17% of arterial FA-concentration. This was accompanied by reduced uptake-rate. Transcapillary diffusion-resistance, unless markedly altering, cannot be responsible for this observation. Calculated diffusion-rates of FA and FA* protein-complexes in the endothelial cytoplasm and interstitium indicate that FA-transfer takes place almost exclusively bound to carrier proteins. The apparent permeability surface-area-values of FA for transendothelial FA-transfer are three orders of magnitude higher than those for sucrose; diffusion-coefficients for FA across the endothelium are close to those in water, excluding substantial diffusion-barrier of the capillary wall. Dissociation-rate-constants calculated from experimental data are in the range of those reported for FA* albumin-complexes in vitro. Thus the observed transcapillary FA-gradients are apparently due to the limited dissociation-rate of the FA*albumin-complex in the intravascular space. PMID- 8340928 TI - Effects of anions and/or cell volume on the permeance of an apical water pathway induced by Hg in toad skin epithelium. AB - Hg compounds block membrane transport units behaving as water channels. Here we show that Hg induces an apical water pathway in toad skins pretreated with 10(-3) M CH3ClHg or HgCl2, added to the outer bathing medium. Washing with SO4-Ringer caused a several-fold increase in net water flow (Jw) and osmotic permeability coefficient (Pf) that was reversed by re-exposure to Cl- or NO3-Ringer and mimicked by gluconate-Ringer. These Pf changes could be elicited repeatedly and were present if, and only if, anion replacements took place in the inner bathing solution. Such inner polarity was related to the anion permeability of the epidermal basolateral membrane: impermeant anions (SO4, gluconate) increased Pf; permeant anions (Cl, NO3) did not change basal Pf but reversed the high Pf induced by impermeant anions. Hg induced the appearance of aggregates that persisted despite repeated washings of the skins during 4-5 h, and whether Pf was high (SO4-Ringer) or low (Cl-Ringer) before skin fixation. The Hg-induced apical water pathway in toad skin appears to be a unique model for studying the interplay between cell volume, cell ionic composition and water permeability. PMID- 8340930 TI - Superoxide dismutase plus catalase therapy delays neither cell death nor the loss of the TTC reaction in experimental myocardial infarction in dogs. AB - Studies to test whether superoxide dismutase (SOD), with or without catalase, limits myocardial infarct size have produced conflicting results. Positive results following short periods of reperfusion vs negative results following longer periods of reperfusion could be explained if either: (1) myocytes, initially salvaged by SOD, are killed by continued production of free radicals after the administered SOD have been excreted, or (2) false positive results occur because SOD transiently preserves the TTC reaction, despite loss of cellular viability. To evaluate these two possibilities, we measured infarct size after 90 min of ischemia and 4 h of reperfusion in SOD+catalase treated and untreated dogs. Treated dogs received a 60 min intra-arterial infusion of SOD (15,000 U/kg) plus catalase (CAT) (55,000 U/kg) beginning 25 min before reperfusion. Infarct size was measured using triphenyl tetrazolium (TTC) macrochemistry and was compared with the extent of necrosis assessed semi quantitatively by light microscopy. Mean infarct size was similar in the control and treated groups. In addition, there was a positive linear correlation (r = 0.95) between the extent of necrosis estimated by microscopy and that estimated by TTC in both groups, and treatment did not alter the regression line. These current results were compared with results from the control dogs from our previous study (Richard et al., 1988) in which 90 min of ischemia was followed by 4 days of reperfusion. TTC-based infarct size at 4 days of reperfusion was similar to that observed in both groups at 4 h. These data indicate that oxygen free radicals, accessible to intravascular SOD and catalase, are not a cause of myocyte death detectable by measurement of infarct size after 4 h of reperfusion. Moreover, neither an "early protection, delayed death" hypothesis nor a specific preservation of the TTC reaction explain the positive results of other studies. TTC macrochemistry provides reliable estimates of myocardial infarct size, provided that sufficient magnification is used to permit resolution of interdigitating peninsulas of viable and necrotic tissue. PMID- 8340931 TI - Effect of transforming growth factor-beta 1 on myocardial stunning in the intact dog. AB - Previous studies have demonstrated that transforming growth factor-beta (TGF beta) can accelerate wound healing, inhibit free radical formation and limit myocardial ischemia/reperfusion injury in a variety of experimental models. However, it is unknown whether exogenous TGF-beta 1 can attenuate the prolonged contractile dysfunction that is observed after a brief, reversible ischemic insult (myocardial stunning). Thus, open-chest dogs undergoing a 15-min left anterior descending coronary artery occlusion and 4 h of reperfusion were given TGF-beta 1 as an intravenous bolus (250 micrograms) at 24 h and again at 1 h before coronary occlusion (n = 5). Control dogs (n = 7) received equivalent amounts of vehicle. The two groups were similar with respect to occluded bed size, collateral blood flow and rate-pressure product. Fundamental physiological parameters, such as body temperature, arterial pH, PO2 and hematocrit, were within normal limits throughout the experiment. In control dogs, regional myocardial function (assessed as systolic thickening fraction) remained depressed throughout the 4 h reperfusion period, indicating severe myocardial stunning. TGF beta 1 did not produce any significant improvement in the recovery of regional function; 4 h after reperfusion, paradoxical systolic thinning was still present in both treated and control groups, with thickening fraction being -22.5 +/- 6.1% and -31.0 +/- 5.3% of baseline, respectively (P = N.S.). These results demonstrate that a large dose of TGF-beta 1 given before ischemia fails to attenuate myocardial stunning in the open-chest dog, suggesting that this growth factor does not exert protective effects in the setting of reversible myocardial ischemia/reperfusion injury. PMID- 8340932 TI - Influence of congestive heart failure on endothelin levels and receptors in rabbits. AB - Congestive heart failure, both in man and in animals is associated with an increased plasma level of endothelin. To investigate further the potential role of the endothelin system, we designed a study to determine the effect of experimental congestive heart failure (CHF) on plasma and tissue immunoreactive endothelin (irET) and on the density and affinity of endothelin-1 receptors in the heart and kidney. For this purpose, CHF was induced in rabbits by combined aortic valvular insufficiency and stenosis. When CHF was established, plasma and tissue irET levels were measured by radioimmunoassay and density and affinity of endothelin-1 receptors were measured by binding assay on tissue homogenates. Compared to control rabbits, plasma irET was significantly elevated in rabbits with CHF [1.04 +/- 0.15 vs. 0.04 +/- 0.01 fmol/ml, P < 0.001]. Tissue irET concentrations in ventricles and kidney were roughly 4 orders of magnitude higher than plasma concentrations. CHF decreased the tissue irET levels in left ventricle and kidney by 32 and 46%, respectively (P < 0.01), whereas CHF increased it by 58% in the right ventricle (P < 0.005). The density of ET-1 receptors was decreased in the right and left ventricles and in kidneys by 26, 36, and 61%, respectively (P < 0.05). Receptor affinity remained unchanged in response to CHF in both ventricles, whereas it increased in kidney [Kd (pM); 154 +/- 17 vs. 99 +/- 9, P < 0.01]. Thus, this study demonstrates that experimental CHF is not only characterized by elevated plasma irET levels but also by a decrease in tissue irET concentrations in the left ventricle and kidney, and by a down-regulation of ET-1 receptors both in the heart and kidney. Functional consequences of these changes need to be determined. PMID- 8340933 TI - A clathrin-coated vesicle-mediated pathway in atrial natriuretic peptide (ANP) secretion. AB - Atrial Natriuretic Peptide (ANP), produced by atrial cardiomyocytes, is an endogenous hypotensive agent that brings about vasodilation and diuresis. Similar to other polypeptide hormones, ANP is synthesized as a precursor, preproANP. The preprohormone is processed intracellularly and is stored in secretory granules as the prohormone. During the events of exocytosis, the prohormone is converted to its active form, ANP. In this study, a double-label immunocytochemistry experiment was performed using ANP and clathrin antibodies to determine if the transport of this hormone is mediated by clathrin-coated vesicles. Additionally, we have isolated clathrin-coated vesicles (CVs) from adult rat atria using immunoadsorption, and have characterized the fraction by using SDS PAGE, TEM, and Western blot analysis. The data demonstrate that: (1) ANP and clathrin co localize in myocardial tissue, (2) clathrin-coated vesicles can be isolated from adult rat atria, and (3) clathrin-coated vesicles isolated from adult atrial myocardium contain predominantly proANP. The presence of proANP in clathrin coated vesicles suggests that this polypeptide hormone is transported intracellularly via a clathrin-mediated pathway and during transit the prohormone is not significantly converted to its active form. PMID- 8340934 TI - Simple 24-hour preservation of rabbit hearts with hexanol and pyruvate cardioplegia. AB - The effectiveness of a newly developed crystalloid cardioplegic solution containing 4 mM 1-hexanol and 10 mM pyruvate was compared with St Thomas' Hospital solution. After control perfusion with a Langendorff method, rabbit hearts (n = 7 for each group) were arrested and stored in these solutions (4 degrees C) for 24 h and subsequently reperfused for 45 min. The hexanol solution preserved both left ventricular systolic and diastolic function significantly better than St Thomas' Hospital solution. Developed pressure was significantly higher after preservation with the hexanol solution than with the St Thomas' Hospital solution at left ventricular balloon volumes larger than the mid volume (P < 0.05). The maximum developed pressure values after storage with the hexanol and St Thomas' Hospital solution were 77% and 42% of the maximum control values, respectively. Values for end-diastolic pressure at the maximum ventricular volume were 26.1 +/- 9.8 and 66.7 +/- 24.6 mmHg for the hexanol and St Thomas' Hospital solution, respectively (P < 0.05). Creatine kinase release during the first 15 min of reperfusion was significantly lower with the hexanol solution as compared to St Thomas's Hospital solution (28.3 +/- 8.3 vs 92.9 +/- 52.6 IU/g wet weight, P < 0.05). In conclusion, a hexanol cardioplegic solution may be suitable for long-term cardiac preservation. Further evaluation of the effectiveness and safety of this solution is warranted. PMID- 8340935 TI - Detection of low molecular weight GTP-binding proteins associated with rat atrial secretory granules. AB - Recent studies suggest that low molecular weight (LMW) GTP-binding proteins are involved in the vesicular transport of proteins along the secretory pathway. In order to determine whether LMW GTP-binding proteins are potentially involved in the regulated secretion of atrial natriuretic factor (ANF) from the atrial myocyte, rat atrial secretory granules were purified and the LMW GTP-binding proteins associated with these granules were detected in [alpha-32P]GTP-blotting experiments. Three LMW GTP-binding proteins, displaying molecular weights of 23,000, 25,000 and 29,000, were usually observed in atrial secretory granule preparations. The 29 kDa GTP-binding protein (G29), however, was typically the predominantly labelled band. The binding of [alpha-32P]GTP to G29 was guanine nucleotide specific and magnesium-dependent. Trypsin treatment of intact secretory granules markedly reduced the binding of [alpha-32P]GTP to G29. G29 is tightly associated with the granule membrane, as evidenced by its resistance to solubilization by high ionic strength buffers but its sensitivity to solubilization with sodium cholate. When secretory granule preparations of rat anterior pituitary glands were examined for the presence of LMW GTP-binding proteins, a different pattern of LMW GTP-binding proteins was observed which did not include a predominantly labelled 29 kDa protein. The results of this study indicate that: (1) LMW GTP-binding proteins are present on atrial secretory granules and may therefore be involved in the regulated secretion of ANF and (2) tissue-specific differences exist between the LMW GTP-binding proteins associated with secretory granules. PMID- 8340936 TI - Effect of a monoclonal antibody to VLA-4 on lymphocyte adherence to microvascular and aortic endothelial cells. AB - Lymphocyte migration out of the blood to inflammatory sites is preceded by the adherence of lymphocytes to the vascular endothelium. This lymphocyte binding is enhanced by cytokine activation of the endothelial cells (EC). Small peritoneal exudate lymphocytes (sPEL) migrate preferentially into cutaneous inflammation and to skin injected with INF gamma, TNF alpha or LPS. These cells adhere also to rat microvascular EC and this adherence correlates well with migratory properties of sPEL. Lymphocyte EC adhesion is in part mediated by the VLA-4 molecule on the lymphocytes. Since differences between microvascular and large vessel EC have been described, we investigated whether sPEL adherence to both types of EC is governed by similar molecular mechanisms. Lymphocyte adhesion was low to unstimulated microvascular EC and augmented by pretreatment of EC with INF gamma, TNF alpha and LPS. In contrast, lymphocyte adhesion to unstimulated large vessel (aortic) EC was higher than to microvascular EC and could not be increased by cytokine or LPS treatment. Anti VLA-4 mAb inhibited the enhanced cytokine stimulated adhesion to microvascular EC without affecting adhesion of sPEL to unstimulated EC. Anti VLA-4 mAb inhibited the high spontaneous adhesion to aortic EC, suggesting that with both EC, adhesion is in part VLA-4 dependent. PMID- 8340937 TI - Strategies for suppressing the function of oncogenic Ras protein in tumors. PMID- 8340939 TI - Imprinted genes play role, change rules, in cancer. PMID- 8340940 TI - Treating cancer pain in kids gets new attention. PMID- 8340938 TI - Gastric cancer following peptic ulcer surgery. PMID- 8340941 TI - Cytotoxic T-cell response and in vivo protection against tumor cells harboring activated ras proto-oncogenes. AB - BACKGROUND: Activated forms of the ras proto-oncogene have been found in approximately 30% of human malignancies, including pancreatic, colon, and lung adenocarcinomas. Ras oncoproteins arise by somatic mutation and contain amino acid changes at residues 12, 13, or 61, thus generating unique tumor-specific proteins that are attractive targets for cancer therapy. PURPOSE: The goal of this study was to determine whether vaccination with mutant Ras protein could lead to the generation of cytotoxic T lymphocytes (CTLs) specific for the mutant epitope and to protection against challenge with tumor cells expressing the mutant oncoprotein. METHODS: To determine a methodology for generating CTL responses following immunization with soluble protein, ovalbumin was used as a model tumor antigen. C57BL/6 mice were immunized with soluble ovalbumin administered intraperitoneally at 2-week intervals or with intravenous injection of ovalbumin or osmotically loaded splenocytes. Immunized mice were challenged with E.G7 cells (which express a transfected ovalbumin gene), and tumor growth was monitored. Generation of ovalbumin-specific CTLs was determined by 51Cr release assays. Purified wild-type or mutant H-Ras proteins (containing single amino acid substitutions at position 12 converting Gly to Arg or Val) were used to immunize BALB/c mice intraperitoneally. Ras-immunized mice were challenged with tumor cells containing Arg 12 or Val 12 mutations or not harboring mutant forms of Ras. Cytolytic and proliferative responses to mutant forms of Ras were studied, and the effects of in vivo depletion of CD4+ or CD8+ T lymphocytes were determined. RESULTS: In vivo challenge with E.G7 showed that intraperitoneal immunization with soluble ovalbumin was as effective as osmotic loading, resulting in long-term disease-free survival of some mice and the development of ovalbumin-specific CTLs. Immunization with Arg 12 Ras led to disease-free survival in nine of 10 animals challenged with tumor cells containing an Arg 12 mutation, while no protection was afforded against tumors expressing other forms of Ras or other oncogenes. Splenocytes from BALB/c mice immunized with Arg 12 Ras demonstrated cytolytic activity specific against tumor cells expressing Arg 12 Ras, with most of this activity residing in the CD8+ subset. Mutation-specific proliferation to Arg 12 Ras peptides was also observed. Immunization with Val 12 Ras did not elicit detectable Val 12-specific immunity. CONCLUSIONS: Antigen specific CTLs can be induced following intraperitoneal immunization of mice with purified, soluble proteins. For both ovalbumin and Arg 12 Ras, specific in vivo protection against tumor cell challenge was observed. PMID- 8340942 TI - A cohort study of stomach cancer risk in men after gastric surgery for benign disease. AB - BACKGROUND: For the past 40 years, investigators have suggested that there exists an increased risk of stomach cancer following gastric surgery for benign disease. Recent cohort studies have consistently identified an increased risk of stomach cancer beginning 20 years or more following gastric surgery. Validation of this association and elucidation of risk factors related to gastric cancer have been complicated by variability in study designs. PURPOSE: This cohort study was designed to investigate the risk of stomach cancer following gastric surgery and to identify patient and treatment characteristics that may alter this risk. METHODS: Medical admission records of 17077 male military veterans hospitalized during 1970-1971 in U.S. Department of Veterans Affairs (VA) hospitals were examined. From this initial cohort, 1094 patients who died within the 1st year following gastric surgery were excluded. Data analysis was performed on the final cohort consisting of 15,983 patients divided into the following two groups: 1) an exposed group (gastric surgery group) that included 7609 patients receiving gastric surgery for a documented benign disorder and 2) an unexposed group (comparison group) that included 8374 male patients randomly selected from all other hospitalized male patients in the patient database. The comparison group was matched to the gastric surgery group by age (within 10 years), race, hospital, and year of admission. Mortality follow-up utilized the following three sources to identify vital status: 1) the VA Patient Treatment File (1970-1988), 2) the VA Beneficiary Identification Record Linkage System (1970-1989), and 3) the National Death Index (1979-1988). Death certificates were obtained for 99% of the deceased patients. Analyses included estimations of risk using standardized rate ratios (SRRs) and proportional hazards techniques. RESULTS: A statistically significant increase in risk of stomach cancer was demonstrated among males during the 20 years following gastric surgery (SRR = 1.9; 95% confidence interval [CI] = 1.3-2.4; P = .0001). The risk of developing gastric cancer was greatest during the 2nd to 5th postoperative years (SRR = 2.8; 95% CI = 1.6-4.5; P < .01) and during years 11-15 (SRR = 2.5; 95% CI = 1.2-4.8; P < .01). Also, the risk of developing gastric cancer was greatest among those treated by gastrectomy for any type of ulcer (SRR = 2.6; 95% CI = 1.2-4.9; P < .01) and those having any type of gastric surgery when the primary diagnosis was gastric ulcer (SRR = 2.9, 95% CI = 1.4-5.3; P < .01). CONCLUSIONS: This study confirms that men undergoing gastrectomy for benign disease and men receiving any gastric surgery for gastric ulcer are at increased risk for developing gastric cancer. Unlike earlier studies, we find that the increased risk is not delayed for 20 years. PMID- 8340943 TI - Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy. AB - BACKGROUND: The high incidence of and mortality from colorectal cancer (160,000 new cases and 60,000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. PURPOSE: This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. METHODS: From 1975 through 1979, a total of 21,756 patients (aged 40 and older) who presented at the Preventive Medicine Institute-Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood test cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12,479 patients were assigned to each group. Patients in both trials had follow up through 1984. RESULTS: Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater (P < .001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance (P = .053, one-sided). CONCLUSIONS AND IMPLICATIONS: The screening of average-risk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment. PMID- 8340944 TI - Phase I trial of granulocyte-macrophage colony-stimulating factor plus high-dose cyclophosphamide given every 2 weeks: a Cancer and Leukemia Group B study. AB - BACKGROUND: Chemotherapy-induced myelosuppression often limits escalation of cancer chemotherapy doses. Cyclophosphamide, an alkylating agent, is an ideal candidate for dose escalation: A log-linear relationship between cell kill and dose has been demonstrated, and the drug spares hematopoietic stem cells. In addition, studies suggest that granulocyte-macrophage colony-stimulating factor (GM-CSF) can enhance the ability to achieve optimal dose intensity as well as ameliorating chemotherapy-induced myelosuppression. PURPOSE: The purpose of this study was to determine the maximum tolerated dose and the toxic effects of cyclophosphamide administered every 2 weeks with GM-CSF support. METHODS: For this trial by the Cancer and Leukemia Group B (CALGB), cohorts of patients were treated with cyclophosphamide as a 1-hour intravenous infusion every 14 days; GM CSF was given subcutaneously on days 3-10. Four dose levels of cyclophosphamide (1.5, 3.0, 4.5, and 6.0 g/m2) and three dose levels of GM-CSF (2.5, 5.0, and 10.0 micrograms/kg per day) were evaluated. There was no dose escalation in individual patients. Fifty-one patients with solid tumors who had CALGB performance status 0 or 1 and minimal prior radiotherapy were eligible for analysis. Drug clearance and area under the curve for plasma drug concentration x time (AUC) were estimated at completion of the infusion and at 4 and 24 hours after the start of the infusion. RESULTS: Ninety-five courses of therapy were analyzed. Treatment with cyclophosphamide at 3.0 g/m2 or more resulted in neutropenia (absolute neutrophil counts < 100/microL) in all cycles of therapy. At those doses, blood cell count recovery adequate for re-treatment occurred in 67%-85% of cycles (median, 16 days). Doses of 6.0 g/m2 were associated with the greatest degree of myelosuppression and frequent hospitalization (88% of cycles); requirements for blood transfusion prohibited further dose escalation. Nonhematologic toxic effects were tolerable, with two episodes of reversible cardiotoxicity and four episodes of hemorrhagic cystitis that precluded further therapy. Degree of myelosuppression was not correlated with cyclophosphamide AUC or clearance. CONCLUSIONS: The recommended phase II dose of cyclophosphamide is 4.5 g/m2 administered every 2 weeks with GM-CSF given at 5.0 micrograms/kg per day of GM CSF. Our results suggest that, with GM-CSF support, high cumulative doses of cyclophosphamide can be given to achieve optimal dose intensity, with reproducible blood cell count recovery and without the need for autologous bone marrow transplantation. IMPLICATIONS: Phase II studies of this intensive regimen in malignant diseases sensitive to alkylating agents are currently being done in CALGB. PMID- 8340945 TI - Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. AB - BACKGROUND: A variety of human tumors frequently express high levels of epidermal growth factor (EGF) receptor and its ligand, transforming growth factor alpha (TGF-alpha), which in some tumors is associated with poor prognosis. Monoclonal antibodies (MAbs) that block the binding of TGF-alpha or EGF to the receptor can inhibit proliferation of tumor cells that express the receptor. Studies suggest that these MAbs may enhance the antitumor effects of chemotherapy. PURPOSE: Our purpose was to study, in vitro and in vivo, the antitumor effects of doxorubicin in combination with anti-EGF receptor MAbs against tumor cells expressing high levels of EGF receptor. Our goal was to achieve maximum initial cytoreduction with high-dose doxorubicin in association with prolonged blockade of EGF receptor with MAbs. METHODS: Anti-EGF receptor MAbs 528 (isotype IgG2a) and 225 (isotype IgG1) were used in combination with doxorubicin against cells from human A431 squamous cell carcinoma and human MDA-468 breast adenocarcinoma. Both A431 and MDA-468 cells express high levels of EGF receptors and TGF-alpha. Cultured cells were treated with doxorubicin (range, 0-10 nM) in the presence or absence of MAb 528 or 225 (range, 0-30 nM). At 48 hours, doxorubicin-containing medium was removed, and treatment with antibody was continued for 5 days, when cell proliferation assays were performed. The activity of the agents and the combinations against well-established xenografts in BALB/c nude mice was also studied. In nude mice, doxorubicin was given at doses of 50-100 micrograms/20 g body weight on 2 successive days, and MAbs 528 and 225 were given at a dose range of 0-2 mg intraperitoneally twice a week. RESULTS: MAbs 528 and 225 both enhanced the antitumor effects of doxorubicin against A431 and MDA-468 tumor cells, producing additive growth suppression in cell cultures. MAb 528 increased the antitumor effects of doxorubicin by 32%-42%, and similar results were obtained with MAb 225. In BALB/c athymic mice, the treatment of well-established xenografts with either doxorubicin or anti-EGF receptor MAb alone temporarily inhibited growth, but the combination of both agents substantially enhanced antitumor activity over that of doxorubicin alone in A431 and MDA-468 cell xenografts. The combination treatment of mice bearing A431 xenografts resulted in tumor eradication of 40%-100% in the surviving mice in several independent experiments. The enhanced antitumor activity was dose dependent. CONCLUSIONS: Our results suggest that anti-EGF receptor MAbs substantially enhance the effects of doxorubicin against well-established xenografts of tumor cells expressing high levels of EGF receptors. IMPLICATIONS: Clinical trials with anti-EGF receptor MAbs are being conducted, and trials with anti-EGF receptor MAbs combined with doxorubicin are planned. PMID- 8340946 TI - Effects of tumor necrosis factor-alpha on muscle-protein turnover in female Wistar rats. AB - BACKGROUND: Many cancer patients experience a wasting syndrome (cachexia) characterized by weight loss and abnormalities in carbohydrate, protein, and lipid metabolism. Recent experimental studies suggest that the development of cancer cachexia involves the host's production of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). PURPOSE: Our goal was to evaluate in rats the effects of an 8-day TNF-alpha treatment on overall protein metabolism in the liver, diaphragm, heart, and hind-leg muscles. METHODS: Four experimental groups corresponding to specific tissues (liver, diaphragm, heart, and hind-leg muscles) in female Wistar rats (100-150 g) were studied. Each group consisted of 25 TNF-alpha-treated and 25 control female Wistar rats. The TNF-alpha-treated rats were given intraperitoneal injections of recombinant-derived human TNF-alpha (0.5 mL) that was administered in two daily injections of 50 micrograms/kg (total dose of 100 micrograms/kg per day) for 8 days. Control animals followed the same injection schedule as the treatment group and received 0.5 mL of physiological saline instead of TNF-alpha. All rats were radioactively labeled with NaH14CO3 24 hours prior to TNF-alpha treatment. At 0, 1, 2, 4, and 8 days during TNF-alpha treatment, five rats per group were killed to measure the radioactive decay of labeled protein in specific tissues in order to estimate fractional protein turnover. During necropsy, the liver, hind-leg muscles (soleus muscle analyzed separately on 8th day only), heart, and diaphragm were rapidly weighed, and each was homogenized. Total protein content and total DNA were also determined. Total protein radioactivity and specific protein radioactivity (per milligram of protein) were evaluated for liver, diaphragm, heart, and hind-leg muscles. Radioactivity was counted in a liquid scintillation counter. Fractional rates of protein synthesis, protein degradation, total protein, and protein accumulation or loss were calculated. RESULTS: The TNF-alpha treatment administered to female Wistar rats for 8 days resulted in a transient decrease in food intake and body weight 24 hours after the beginning of the TNF-alpha treatment. In all types of tissues studied, TNF-alpha treatment resulted in increases in both the protein synthesis and protein degradation, with a greater increase in the protein degradation that resulted in a reduced protein accumulation following TNF-alpha treatment. This reduction in protein accumulation was directly associated with a decreased soleus muscle mass on day 8 of the treatment. CONCLUSIONS: Data suggest that TNF-alpha enhances muscle degradation in experimental situations where body weight loss is not apparent. PMID- 8340947 TI - Cancer breakthroughs require mavericks. PMID- 8340948 TI - Tamoxifen-induced decreases in total cholesterol with 2 weeks of treatment. PMID- 8340949 TI - The effects of hyperthyroidism on MIBG uptakes in the human heart--preliminary report. AB - Twelve cases of hyperthyroidism with cardiac manifestations (4 males, 8 females, ages: 20 to 70 years) and 12 normal controls of euthyroidism (6 males, 6 females, ages: 27 to 70 years) were included in our study. Each case accepted an I.V. injection of I-131 MIBG (I.R.E., Belgium) with 0.5mCi/1.7m2 of body surface area. The 24 and 48 hr imagings of the anterior chest, including total heart and lungs, were used to estimate cardiac sympathetic nerve innervation by the following formula: H/L = (the mean counts of pixels in the regions of interest (ROI) over the heart)/(the mean counts of pixels in the ROI over the lungs). The results showed that the 24 and 48 hr H/L values in euthyroidism were a little higher than those in hyperthyroidism, but the differences were not significant by a Wilcoxon rank sum test. The correlation between H/L and 24 hr I-131 thyroid uptake in patients with hyperthyroidism were also evaluated and the results showed no significant correlation between the H/L and uptake. In conclusion, we consider that the clinical manifestations concerning the heart in hyperthyroidism may not totally depend on the effects of increased cardiac sympathetic nerve innervation. PMID- 8340950 TI - Bilateral simultaneous hypertensive intracerebral hemorrhages. AB - Bilateral simultaneous hypertensive intracerebral hemorrhages (HICH) are a rare occurrence. Computed tomography (CT) enables us to diagnose such a condition which is difficult to recognize clinically. In the series, six patients (2.6%) from a series of 553 HICH cases had suffered from simultaneous rehemorrhage in the contralateral hemisphere. It comprised four males and two females. Their ages ranged from 54 to 64 years with a mean age of 58 years. The clinical symptoms were excessively sever and were characterized by severe consciousness disturbance (semicoma to coma, 6 cases), aphasia (5 cases) and bilateral paresis (3 cases). CT density profiles were identical, implying that the hematomas were of similar age but located areas; two were bilateral basal ganglia, one was bilateral specular thalamus, pontine-ganglia (right), thalamo (left)-ganglia (right) and occipito (right)-thalamus (left) individually. All of the hematomas had ruptured into the ventricles. The predominant sites of hemorrhage were in the putamen (50%, 6/12) and the thalamus (33%, 4/12). Two patients received emergency craniotomy for evacuation of the hematomas. However, they died soon after the operations. In the remaining four non-surgical cases, two died of central failure, another died of pneumonia and the remain one survived but retained hemiplegia sequelae. The serious surgical results and outcome in bilateral HICH was compared that of unilateral HICH. Hemodynamically, poor cerebral blood flow and diaschisis phenomenon may contribute to the poor prognosis in these patients. PMID- 8340951 TI - A study of hospital nurses' attitudes toward continuing education in Kaohsiung City, Taiwan. AB - The purpose of this study was to investigate hospital nurses' attitudes toward continuing education. Continuing education was defined as non-credit organized educational programs designed for nurses by hospitals, nursing institutions, or other related organizations to maintain or improve professional competence. It included "in-service education", "on-the-job training", and other synonymous educational activities. Six hundred and seventy-four randomly selected hospital nurses in Kaohsiung City participated in this study. The data was collected by delivering a 34-statement questionnaire through the directors of nursing. Cronbach's Alpha Coefficient was applied to determine the reliability with a value of 0.79. Factor analysis and a group of experts' suggestions were applied to determine the validity. Frequency distribution, Analysis of Variance, Scheffe' test, and Multiple Regression Analysis were conducted to analyze the research questions. The level of significance was set at 0.05 or less. The results indicated that the majority of nurses (92.65%) hold positive attitudes toward continuing education (M = 86.32). Nurses' attitudes toward continuing education were related to selected personal and professional characteristics, and hospital policies regarding continuing education. To maintain nurses' positive attitudes and to develop positive attitudes for those who hold negative attitudes, some strategies for continuing education should be considered by nursing administrators. PMID- 8340952 TI - [A preliminary report about body shape and composition of 300 citizens in Kaohsiung City]. AB - We studied 300 healthy citizen of Kaohsiung City, Taiwan, to discover factors that affect body shape, and especially body weight. It's our hope that we could find an objective evaluative index to assess obesity that would be suitable for use in out-patient clinics. During the study period, 300 healthy, under 50 years old volunteers were participated in our study. All the participant were asked to completed a questionnaire and anthropometric measures for analysis. The result of our study showed that age, sex and drinking habit all were significantly affected body shape. We also found that relative body weight and subscapular skinfold thickness are best predictor of body fat composition. Therefore, we suggest the combined use relative body weight and subscapular skinfold thickness as an index for assessing obesity in out-patient clinics. PMID- 8340953 TI - [Factors affecting stroke patients' motivations for rehabilitation]. AB - Factors correlated to the motivation for rehabilitation in stroke patients were studied. Thirty patients who had had only one stroke were recruited between December 1991 and April 1992 for our study. Several assessment tools including the Motivational scale, the Health Locus of Control scale and a questionnaire were used. According to the results of the assessment, the stroke patients' motivation remained stable when assessed two to three times during the hospital stay, whereas their UE/LE Brunnstrom stage scores and activities of daily living skill (ADL) improved significantly. The motivation of the patients was closely correlated with the degree of education, the internal scores and ADL performance: patients with education level higher than primary school, higher internal scores, or better ADL performance had stronger motivation for rehabilitation. On the other hand, motivational assessments between the nursing staff and the therapists were not completely in agreement. The ADL performance was better correlated with the degree of motivation on the nursing assessment, whereas the Brunnstrom stage scores of UE/LE were more closely correlated with the therapists' assessment. Items on the motivational questionnaire such as "eagerness to recover earlier", "recognition of the effectiveness of rehabilitation", "support of spouse" and "homesickness" were commonly considered to be positive factors. However, the other factors such as "being in bad mood", "lack of family cooperation", "worrying about things other than finances" and "lack of family support" were commonly considered to be negative factors on motivation. In the comparison between high and low motivation groups, the high motivation group payed more attention to the positive factors such as "eagerness to be independent" and such negative factors as "lack of understanding of illness" as well as "poor appetite and fatigue". The low motivation group was considered to be more affected by such negative factors as "worrying about things other than finances", "not good enough facilities" and "homesickness" which resulted in lessening the motivation for rehabilitation. PMID- 8340954 TI - Metastatic brain tumor manifesting as lacunar syndrome in adults. AB - Lacunar syndrome can be an initial manifestation of the metastatic brain tumor in young adults. Two patients were encountered with previously undiagnosed lung cancer, one with anaplastic carcinoma and the other with adenocarcinoma. A neurologic syndrome occurred in the morning with unusual headache and stroke-like episodes, presenting an acute ataxic hemiparesis and a pure motor hemiparesis, respectively. Papilloedema was a universal finding. The headache and neurologic deficits responded rapidly to glucocorticoid. A preexisting intracranial mass with an outburst of brain edema is thought to be the mechanism in this situation. PMID- 8340955 TI - Extracranial internal carotid artery dissection secondary to neck massage: visualization of mural hematoma by MRI. AB - A 52-year-old man was admitted due to a severe pain in the right side of the neck and a progressive weakness of the left-side extremities. One week prior to admission, the patient began to use massage balls to relieve his long-lasting nuchal soreness. Carotid arteriography revealed a segment of tapered stenosis of the extracranial internal carotid artery with distal occlusion at the proximal middle cerebral artery. Magnetic resonance imaging (MRI) demonstrated a well defined mural hematoma which is a distinctive feature of arterial dissection. PMID- 8340956 TI - Cast-model and scanning electron microscopy of the rat brain ventricular system. AB - In order to establish a good experimental model for comparative studies of the brain ventricular system in mammals, a resin-cast model and scanning electron microscopy were employed to examine the rat brain ventricular system. From the resin-cast model, we found that the gross morphology of the brain ventricular systems of rats is simpler than that of humans. From scanning electron microscopy, local variations of ependymal cells lining the rat brain ventricle were noted. Most areas of the ventricles were lined by ciliated ependymal cells arranged in regular rows, whereas in some other areas non-ciliated ependymal cells were also observed. Epiplexus cells and supraependymal cells were also encountered on the top surface of the choroid epithelium, and ependymal cells in certain area such as the pineal recess. PMID- 8340957 TI - Solid phase radionuclide esophageal motility in polymyositis and dermatomyositis. AB - Polymyositis (PM) and dermatomyositis (DM) may be associated with motor dysfunction of the entire gastrointestinal tract. Abnormal esophageal motor function is a well-recognized complication of these diseases. In this study, we used a solid phase esophageal study to evaluate the motor function in patients with PM or DM. Twenty-three patients and 36 age-matched normal volunteers were studied. Each subject was placed in a supine position above a gamma camera linked to a computer and was given a 4-ml bolus of solid gelatin containing 1 mCi of Tc 99m phytate. Data were acquired in the list mode. A computer method modified from Kelim and Wald and Russell et al. was used to calculate the following: A) total mean transit time (MTT); B) residual fraction after the first swallow (RF); and C) retrograde index (RI). All values are presented as mean +/- standard deviation (SD). The Student's t-test was used to test statistical significance. Our preliminary results suggest: 1) delayed esophageal emptying is common (17/23) in PM/DM, indicating frequent malfunction of the smooth muscle of the upper gastrointestinal tract in PM/DM and 2) measurement of esophageal motility may monitor disease activity in PM/DM. PMID- 8340958 TI - [Value of fine needle aspiration cytology in the diagnosis and management of fibroadenoma of the breast]. AB - Cytological and histopathological biopsies were obtained from 121 breast lumps clinically diagnosed as fibroadenomas. Of these 98.3 percent of the lesions were benign. The cytological diagnosis was benign in 95.1 percent of 101 (83.4% of total) cases confirmed as fibroadenomas, histopathologically, but inadequate for diagnosis in 4.9 percent. The remaining 20 lesions included one breast cancer and one primary malignant lymphoma. In this group aspiration cytology was inadequate for diagnosis in 20 percent of the cases (P < 0.05). The cytological reports cast suspicion in the two malignant cases. No lesion with benign cytology was subsequently shown to be malignant. Ninety-five (78.5%) cases of the lesions, representing 72 women under 35 years of age, which has been clinically diagnosed as fibroadenomas, showed fibroadenoma, histopathologically, in 89.5% of these cases. The other 26 (21.5%) lesions in 21 patients, who were over 35 years in age, had 61.5 percent fibroadenomas, cytological results cast suspicion of fibroadenoma in 87.1 percent of these cases. The other 16 histopathologically diagnosed fibroadenomas in patients over 35 years of age showed 62.5% were cytologically suspected of being fibroadenomas (P < 0.025). As a result of this study it is reasonable to suggest that a typical clinical fibroadenoma can be treated conservatively in women under 35 years, but only if an adequate cytological smear obtained by fine needle aspiration does not show malignant of suspicious cells. PMID- 8340959 TI - [Investigation of activity of daily living performance in patients with Duchenne muscular dystrophy]. AB - The purpose of this study was to reach a better understanding the deficits of activity of daily living (ADL) skills in patients with Duchenne muscular dystrophy (DMD), and their influencing factors. Our samples consisted of 35 male DMD patients, aged 3-24 years. The Barthel index was used to assess daily living abilities. Besides ten different motor abilities, muscle strengths of both upper and lower extremities and joint contractures were also included in each patient's evaluation. The results of degree of severity in ADL performance showed that 21.1% of patients were classified as totally dependent, 48.5% were severely dependent, 12.1% moderately dependent, 9.1% mildly dependent and 9.1% totally independent. Among the ADL skills, the bathing needed most assistance whereas feeding required the least. Two of the sixteen factors influencing ADL performance was calculated to be significant after stepwise multiple regression analysis. They were hip contracture and static sitting balance. In conclusion, we find that DMD patients are highly dependent in carrying out ADL tasks. Therefore, it is very important to avoid contracture, to increase static sitting balance and to use appropriate devices to improve their daily living abilities. Finally, the Barthel index proved acceptable in evaluating Taiwanese children over six years of age. PMID- 8340960 TI - [Staffing levels and patient needs in the intensive care unit]. AB - The current study sought to utilize a patient classification system to investigate staffing and patient needs along with nursing care distribution in our intensive care units. The study employed a factor type analysis to design a patient need checklist (for our six ICUs) in order to determine staff load and nursing requirements. Snapshot observations were also taken to survey the distribution of nursing care time. The results of the two methods provide an estimate of current staffing needs, they also show that there is no significant difference between our surgical and internal medicine wards. On average, direct care accounts for 40.1% of the time schedule; indirect care, 37.3%; related care, 6.0%; and individual time, 16.6%. The average patient grade lies between I and III; and workload index, between 4.4 and 11.5. The average nursing time per patient per shift is 2.88 hours, and the average workload per person is estimated at 5.7-5.8 hours. By comparing the number of personnel currently employed and the estimated number needed, we discovered that two units are understaffed, and three are overstaffed. The understaffed units are all surgical units; the overstaffed ones, internal medicine units. To conclude the study, we examined the nature and complexity of nursing duties in the hopes of returning non-nursing responsibilities to the proper medical organizations. Our ultimate goal is to realize the full potential and improve the quality of our nursing personnel. PMID- 8340961 TI - Unilateral symptomatic palatal myoclonus: MRI evidence of contralateral inferior olivary lesion. AB - Symptomatic palatal myoclonus is a rare syndrome of segmental myoclonus which is thought to occur after damage to certain brainstem or cerebellar structures. We report two patients with unilateral PM, who showed hypertrophy of the inferior olivary nucleus on magnetic resonance imaging. In the first patient this was due to a left pontine tegmental hemorrhage, and a right-sided oculo-palato-facial myoclonus developed one month after the episode. The second one had a basilar artery occlusion with ischemic infarcts at the basis pontis, dorso-lateral aspects of the left pons, and left cerebellar dentate nucleus, as well as the occipital lobe. A delayed left oculopalatal myoclonus was recognized 3 months later. Interruption of the "dentato-rubro-olivary pathway" by the lesion with ensuing neuronal loss, cytoplasmic vacuolation, and astrocytic proliferation in the inferior olive, together with an increase of water content as mobile proton may cause the MR signal abnormalities in patients with unilateral symptomatic palatal myoclonus. PMID- 8340963 TI - [Stress fracture of the ribs in amateur golfers diagnosed by Tc-99m MDP scintigraphy]. AB - Golf has become a popular sport in Taiwan recently. Some amateur golfers suffer from back or chest pain, and a few of them have stress fractures of the ribs. Six amateur golfers suffering from back pain or chest pain, all male and right-handed players, aged from 28 to 39, were included in our study. The initial chest roentgenograms, including special views focusing on ribs, were all negative. Tc 99m MDP bone scan confirmed the diagnosis of stress fractures of the ribs. The intervals between playing golf and time of diagnosis were from 1 month to 5 months. In five cases, fracture sites in the left side were prominently located in the posterior aspect, a condition which may result from traction of the serratus anterior. Three cases with fracture sites in the right side had fractures prominently located in the lateral aspect, which may result from the repercussive force produced by the clubhead hitting the ground. Tc-99m MDP bone scan, with its high sensitivity, is useful in establishing the diagnosis of stress fracture. PMID- 8340962 TI - [Teratoma of testis--a case report]. AB - A case of mature testicular teratoma in a 5-year-old child is presented. The level of serum beta-human chorionic gonadotropin (beta-HCG), alpha-fetoprotein (alpha-AFP), and carcinoembryonic antigen (CEA) were all within normal limit one year post-operatively. We discussed the clinical features, treatment and the result of this patient and reviewed the literature. PMID- 8340964 TI - Rational suicide: no longer 'crazy'? PMID- 8340965 TI - Studies raise doubts about benefit of athletics in reducing unhealthy behavior among adolescents. PMID- 8340966 TI - World Bank report says reallocate resources. PMID- 8340967 TI - Pesticides pose concern about children's diet. PMID- 8340968 TI - From the Surgeon General, US Public Health Service. PMID- 8340969 TI - From the Centers for Disease Control and Prevention. Lead poisoning associated with use of traditional ethnic remedies--California, 1991-1992. PMID- 8340970 TI - From the Centers for Disease Control and Prevention. Severe isoniazid-associated hepatitis--New York, 1991-1993. PMID- 8340971 TI - From the Centers for Disease Control and Prevention. Heat-related deaths--United States, 1993. PMID- 8340972 TI - Declining blood lead levels and cognitive change in children. PMID- 8340973 TI - Declining blood lead levels and cognitive change in children. PMID- 8340974 TI - Declining blood lead levels and cognitive change in children. PMID- 8340975 TI - Soil abatement and lead levels in children. PMID- 8340976 TI - Breast-feeding: time to teach what we preach. PMID- 8340977 TI - Breast-feeding: time to teach what we preach. PMID- 8340978 TI - Breast-feeding: time to teach what we preach. PMID- 8340979 TI - Ethnicity and emergency department analgesia. PMID- 8340980 TI - Ethnicity and emergency department analgesia. PMID- 8340981 TI - Controlling the tuberculosis epidemic: the analogy with mental illness. PMID- 8340982 TI - Patients' ratings of outpatient visits in different practice settings. Results from the Medical Outcomes Study. AB - OBJECTIVE: To determine how patients in different kinds of practices--solo or single specialty (SOLO), multispecialty group (MSG), or health maintenance organizations (HMOs)--and with fee-for-service (FFS) or prepaid physician payment arrangements evaluate their medical care. DESIGN: Survey of adult outpatients after office visits, with sample weighted to represent population of patients visiting physicians in each practice type. SETTING: Offices of 367 internists, family practitioners, endocrinologists, cardiologists, and nurse practitioners, in HMOs (prepaid only), MSGs (prepaid and FFS), and SOLO practices (prepaid and FFS). PATIENTS: Adults (N = 17,671) at start of the Medical Outcomes Study. OUTCOME MEASURES: Overall rating of the visit (five choices from excellent to poor). A random half of the sample also rated the provider's technical skills, personal manner, and explanations of care as well as time spent during the visit, the appointment wait, the office wait, the convenience of the office location, and telephone access. RESULTS: Fifty-five percent of patients rated their visit overall as excellent, 32% very good, 11% good, and 2% fair or poor. Patients of SOLO practitioners were more likely (64%) to rate their visit excellent than MSG (48%) or HMO (49%) patients (P < .001). Patients of SOLO practitioners rated all aspects of care better than HMO patients did, most markedly appointment waits (64% vs 40% excellent; P < .0001) and telephone access (64% vs 33% excellent; P < .0001). Within SOLO and MSG practices, FFS patients rated most specific aspects better than prepaid patients, but these differences were not statistically significant and were inconsistent across cities. Adjusting for patients' demographics, diagnoses and self-rated health did not change results. Physicians with visit ratings in the lowest 20% were nearly four times as likely to be left by patients within 6 months than physicians in the highest 20% (16.7% vs 4.6%; P < .001). CONCLUSION: Of the five practice type and payment method combinations, SOLO FFS patients rated their visits best and HMO patients worst. Whether FFS or prepaid, care was rated better in small than in large practices. Our study shows that a brief visit rating form can be used to compare practice settings and health plans, and that patient ratings predict what proportion of patients, on average, will leave their physicians in the next several months. PMID- 8340983 TI - Calcium supplementation and bone mineral density in adolescent girls. AB - OBJECTIVE: To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls. DESIGN: A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass. SUBJECTS: Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry. SETTING: University hospital in a small town. INTERVENTIONS: Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills. MAIN OUTCOME MEASURES: Bone mineral density and bone mineral content of the lumbar spine and total body were measured by dual-energy x-ray absorptiometry and calcium excretion from 24-hour urine specimens. RESULTS: Calcium intake from dietary sources averaged 960 mg/d for the entire study group. The supplemented group received, on average, an additional 354 mg/d of calcium. The supplemented group compared with the placebo group had greater increases of lumbar spine bone density (18.7% vs 15.8%; P = .03), lumbar spine bone mineral content (39.4% vs 34.7%; P = .06), total body bone mineral density (9.6% vs 8.3%; P = .05), and 24-hour urinary calcium excretion (90.4 vs 72.9 mg/d; P = .02), respectively. CONCLUSIONS: Increasing daily calcium intake from 80% of the recommended daily allowance to 110% via supplementation with calcium citrate malate resulted in significant increases in total body and spinal bone density in adolescent girls. The increase of 24 g of bone gain per year among the supplemented group translates to an additional 1.3% skeletal mass per year during adolescent growth, which may provide protection against future osteoporotic fracture. PMID- 8340984 TI - The effect of hospital financial characteristics on quality of care. AB - OBJECTIVE: To assess the relationship among hospital financial characteristics, patient payer mix, and the incidence of negligent medical injuries. DESIGN: Retrospective medical record review linked to hospital financial reports. SETTING: Acute care hospitals in New York State in 1984. POPULATION: Stratified, random sample of 30,195 medical records from 51 acute care hospitals. MAIN OUTCOME MEASURES: Hospital rates of medical injury and substandard care were developed from reviews of 30,195 medical records at 51 acute care hospitals in New York in 1984. Hospital-level variables representing financial status, hospital staffing, and the proportion of self-pay and Medicaid hospital discharges were compiled from a variety of secondary sources. RESULTS: The likelihood of negligent medical injury was highest in those hospitals with the lowest inpatient operating costs per hospital discharge (odds ratio, 2.8; 95% confidence interval, 1.5 to 5.5). The effect of low inpatient operating costs was marked among hospitals in financial distress, many of which served indigent populations. CONCLUSIONS: Patients admitted to hospitals that are unable to expend sufficient resources on patient care may be at higher risk of substandard care. Further study of the effect of hospital financial status on quality of care appears to be warranted. PMID- 8340985 TI - Topical anesthesia during circumcision in newborn infants. AB - OBJECTIVE: To determine the efficacy of topical anesthetic cream, eutectic mixture of local anesthetics (EMLA), in alleviating pain from neonatal circumcision. DESIGN: Randomized, controlled trial. SETTING: Normal newborn nursery in a university teaching hospital. PATIENTS: Twenty-seven newborn, full term male neonates, aged 1 to 3 days. OUTCOME MEASURES: Heart rate, transcutaneous oxygen saturation, facial activity, and crying. RESULTS: Compared with baseline, all newborns experienced pain as evidenced by increased heart rate of an average of 40 beats per minute (F [8, 25] = 14.12; P < .0001), decreased oxygen saturation of 3% (F [8, 25] = 15.02; P < .0001), and more facial actions indicative of pain (F [8, 25] = 5.25; P < .002) during all phases of the procedure. Compared with placebo, EMLA significantly attenuated the pain response as shown by lower heart rate of an average of 25 beats per minute (F [1, 25] = 14.92; P < .001), higher oxygen saturation of 5%, particularly during the clamping and lysis phases (F [1, 25] = 19.83; P < .0001), 20% less facial activity (F [1, 25] = 12.01; P < .002), and 15% less crying during the clamping, Gomco clamp application, and incision of the foreskin. There were no differences between groups in the spectral crying parameters. CONCLUSIONS: Circumcision procedure produces pain responses that EMLA diminishes. Thus, EMLA may be a useful agent for pain management in neonatal circumcision. PMID- 8340986 TI - Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. AB - Convulsive status epilepticus is an emergency that is associated with high morbidity and mortality. The outcome largely depends on etiology, but prompt and appropriate pharmacological therapy can reduce morbidity and mortality. Etiology varies in children and adults and reflects the distribution of disease in these age groups. Antiepileptic drug administration should be initiated whenever a seizure has lasted 10 minutes. Immediate concerns include supporting respiration, maintaining blood pressure, gaining intravenous access, and identifying and treating the underlying cause. Initial therapeutic and diagnostic measures are conducted simultaneously. The goal of therapy is rapid termination of clinical and electrical seizure activity; the longer a seizure continues, the greater the likelihood of an adverse outcome. Several drug protocols now in use will terminate status epilepticus. Common to all patients is the need for a clear plan, prompt administration of appropriate drugs in adequate doses, and attention to the possibility of apnea, hypoventilation, or other metabolic abnormalities. PMID- 8340987 TI - Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. AB - Abetalipoproteinemia is a rare genetic disease that has provided important new insights into the physiology of lipoprotein assembly and vitamin E metabolism. Forty-two years after its initial description, a molecular etiology of ABL has been reported to be a deficiency of a microsomal transfer protein, thus suggesting that this protein plays a key role in lipoprotein particle assembly and secretion both in the intestine and in the liver. Furthermore, studies in patients with ABL have established the critical role of hepatic secretion of VLDL in the delivery of vitamin E to peripheral tissues and the essential role of vitamin E in the maintenance of normal physiological function of multiple tissues. The systematic investigation of this rare genetic disease has provided insights that have substantially enhanced our understanding of human physiology. PMID- 8340988 TI - Doctor, I want to die. Will you help me? PMID- 8340989 TI - Compassion needs reason too. PMID- 8340990 TI - Self-determined death, the physician, and medical priorities. Is there time to talk? PMID- 8340991 TI - Radiation from digital clocks. PMID- 8340992 TI - Treatment for cramping of peripheral vascular occlusive disease. PMID- 8340993 TI - Does recombinant human erythropoietin accelerate erythropoiesis for predonation before cardiac surgery? AB - This study was performed to determine the effect of recombinant human erythropoietin (rEPO) on preoperative autologous blood donation in patients undergoing elective coronary bypass or valvular operations. Nineteen patients received 200 u/kg of rEPO intravenously 3 times a week, and 210 mg/day of iron sulfate orally, for 2 weeks before surgery (EPO group). Seven matched patients only took the same dose of iron sulfate (control group). Bone marrow was aspirated from the sternum during surgery, and the Myeloids/Erythroids ratio was calculated in 13 patients of the EPO group. The total donated blood mass was 853 +/- 231 g in the EPO group, and 657 +/- 140 g in the control group (p < 0.05). The average increase in hemoglobin (Hb) mass from admission to the day before surgery was 87 +/- 33 g in the EPO group, and 24 +/- 13 g in the control group (p < 0.001). Furthermore, the logarithm of the ratio of "increased Hb mass/Hb mass at admission" was significantly correlated to the Myeloids/Erythroids ratio (r = 0.9130, p < 0.01). These results strongly indicate that rEPO is a very useful agent for predonation of autologous blood for cardiac operations. PMID- 8340994 TI - Abnormal postexercise systolic blood pressure response is a good indicator of impaired left ventricular filling during supine cycle ergometer exercise in patients with coronary artery disease. AB - To determine whether the postexercise systolic blood pressure (SBP) response is a useful marker of left ventricular filling abnormalities, supine leg exercise testing was conducted in 14 control subjects and 70 patients with coronary artery disease (CAD). An abnormal postexercise SBP response (the ratio of SBP after 3 min of recovery to the peak exercise SBP) was defined as 0.85 or more, which represented the cutoff point with the highest sensitivity and specificity for prediction of pulmonary artery wedge pressure (PAWP) of at least 20 mmHg at peak exercise in CAD patients. There was a significant difference between the SBP ratios of the two groups (Control, 0.72 +/- 0.05; CAD, 0.86 +/- 0.13; p < 0.01). There was no significant difference between the PAWP of the two groups at rest, but the PAWP at peak exercise was significantly higher in the CAD group (20.2 +/- 8.9 mmHg) than in the control group (11.5 +/- 4.0 mmHg)(p < 0.01). PAWP at peak exercise was > or = 20 mmHg in 35 (50%) of the 70 CAD subjects. The SBP ratio was significantly correlated with PAWP at peak exercise (r = 0.67, p < 0.01) in the CAD group, but not in the control group. An SBP ratio of > or = 0.85 showed a sensitivity of 80% and a specificity of 80% for predicting a peak exercise PAWP of > or = 20 mmHg in CAD patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340995 TI - Usefulness of serum CA125 measurement for monitoring pericardial effusion. AB - To investigate the clinical significance of carbohydrate antigen 125 (CA125), an antigen related to ovarian cancer, in patients with pericardial effusion, we examined the relationship between serum levels of CA125 and the presence or severity of pericardial effusion. Fifty-seven patients (25 with heart failure, 22 with pericardial metastasis, 4 with hypothyroidism, 4 with renal failure, and 2 with other diseases) in whom pericardial effusion was confirmed by echocardiography or autopsy, were used as subjects. Thirty-seven of these patients (65%) tested positive for CA125 in the serum. Of these, no significant differences in serum levels of CA125 were found between patients with benign and those with malignant underlying diseases or between those with, or without, pericarditis. However, CA125 values were higher in the patients with larger pericardial effusions and the serum level decreased when the pericardial effusion reduced. In some cases, the serum level normalized before the effusion resolved. Pericardial drainage was performed on 6 patients with cardiac tamponade. Four of these 6 patients had high serum CA125 levels and recurrent pericardial effusion. The other 2 patients had normal serum CA125 levels and no recurrence of effusion. An immunohistological study showed that a positive stain of pericardial tissues reacting to CA125 antibodies correlated to higher serum and pericardial fluid levels of CA125 than the levels of groups staining negative to the antibody. These results suggest that CA125 can be useful in assessing the status and clinical course of this disease. PMID- 8340996 TI - Effects of volume and pressure overloads and myocardial hypertrophy on exercise induced changes in electrocardiographic QRS amplitude. AB - To investigate the effects of volume and pressure overloads and myocardial hypertrophy on exercise-induced changes in QRS amplitude, we reviewed treadmill exercise electrocardiograms. In 10 normal young men, Rv5 amplitude decreased and Sv1 amplitude increased at peak exercise, and returned to the resting value in the recovery period. In 10 patients with aortic regurgitation, Rv5 and Sv1 amplitudes increased after 5 min of recovery. In 12 patients with essential hypertension and 10 with idiopathic hypertrophic non-obstructive cardiomyopathy, Rv5 amplitude remained unchanged or higher at peak exercise compared with the resting value, but patterns of serial changes were similar to that of normal subjects. In 9 patients with atrial septal defect, R'v1 amplitude increased with exercise, whereas it remained unchanged in 12 with isolated complete right bundle branch block. In 5 patients with mitral stenosis, Sv1 amplitude decreased at peak exercise. In conclusion, changes in QRS amplitude with exercise are influenced by hemodynamic abnormality and myocardial hypertrophy, and a major determinant of these serial changes seems to be the change in ventricular volume. PMID- 8340997 TI - Cumulative effects of heart beat on ventricular premature contractions suggesting possible involvement of triggered activity. AB - We analyzed 24 h ECG recordings of 29 patients with frequent (> 2000/day) ventricular premature contractions (VPCs) to evaluate: 1) the relationship between VPC frequency and heart rate (HR); 2) the relationship between the coupling interval (CI) of VPCs and HR; 3) the time course of changes in VPC frequency following an abrupt and sustained increase in HR; and 4) the effect of oral diltiazem (90 or 180 mg/day for 4 weeks) on VPCs. Based on the patterns of relationship between VPC frequency and HR, patients were divided into 2 groups: 1) 17 patients with a positive correlation, the P group (a linear increase in VPCs with increasing HRs); and 2) 12 patients with a non-positive correlation, the NP group. The NP group showed either a linear decrease in VPCs with increased HRs (4 patients) or an increase in VPCs at low HRs and a decrease at high HRs (8 patients). In all cases, an increased HR was associated with a shortening of CI. In the P group, changes in VPCs after an abrupt increase in HR showed 2 types: 1) delayed-ascent type, in which VPCs increased as the duration of HR increase was prolonged (cumulative effects of heart beat) (7 patients); and non-delayed-ascent type (10 patients). Diltiazem reduced VPCs > or = 75% in all of the 7 delayed ascent-type patients, compared with 3 of the 10 non-delayed-ascent-type patients (p < 0.05) and none of the 12 patients in the NP group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8340998 TI - Assessment of ejection fraction of the right and left ventricles in patients with acute myocardial infarction by magnetic resonance imaging. AB - Right and left ventricular function in acute myocardial infarction (AMI) was assessed by ECG-gated magnetic resonance imagine (MRI) in 64 patients and 8 volunteers. Five short axis images for intrinsic cardiac long-axis of the left ventricle were obtained at 9 msec and 309 msec after the R wave as end-diastole and end-systole. Right and left ventricular volumes were measured by Simpson's rule. The intraobserver variabilities in right and left ventricular ejection fraction (RVEF: r = 0.94, LVEF: 0.89) were excellent. The interobserver variabilities in RVEF (r = 0.61) and LVEF (r = 0.77) were fair. LVEF, but not RVEF, was significantly reduced in patients with AMI. Among left ventricular dysfunction (LVEF < or = 40%) patients, 50% exhibited right ventricular dysfunction (RVEF < or = 40%). Among patients without left ventricular dysfunction, only 12% exhibited right ventricular dysfunction. In left ventricular and biventricular dysfunction compared with control, the left ventricular end-diastolic volume index increased (65 +/- 10 ml/m2, 68 +/- 12 ml/m2 vs 54 +/- 8 ml/m2), the end-systolic volume index increased (40 +/- 16 ml/m2, 43 +/- 7 ml/m2 vs 18 +/- 1 ml/m2), and the right ventricular end-diastolic volume index decreased (52 +/- 13 ml/m2, 53 +/- 20 ml/m2 vs 65 +/- 8 ml/m2). MRI can thus be used to assess ventricular systolic function. Since patients with left ventricular dysfunction revealed a high incidence of right ventricular dysfunction, an interaction between the left and right ventricles may occur in ventricular dysfunction. PMID- 8340999 TI - Effects of propranolol and diltiazem on the rate of high-energy phosphate metabolism in reperfused rat hearts--31P-NMR saturation transfer study. AB - The relationships between pressure rate product (PRP) and flux (PCr-->ATP) or flux (Pi-->ATP) were studied in isolated perfused rat hearts by the saturation transfer method using 31P-NMR. The effects of propranolol and diltiazem on phosphate metabolism were also studied. After a 40 min preischemic period, the hearts were subjected to a 15 min period of ischemia, followed by 60 min of reperfusion. Propranolol (0.4-1.2 microM) or diltiazem (3.0-6.0 microM) was infused for 30 min before ischemia and reinfused after reperfusion for 60 min. The flux (PCr-->ATP)/PRP ratio at reperfusion did not differ from that at preischemia. This value was also not affected by propranolol or diltiazem treatment. However, the flux (Pi-->ATP)/PRP ratio at reperfusion was significantly less than that at preischemia. Moreover, this value was significantly improved by propranolol or diltiazem treatment. This study demonstrates that 1) flux (PCr-->ATP) has a good correlation with cardiac performance, 2) stunned myocardium needs less ATP turnover for survival of its depressed contractile activity, and 3) flux (Pi-->ATP) can limit recovery of postischemic performance. Protective effects of propranolol and diltiazem are exerted on the flux (Pi-->ATP), i.e. ATP derived from glycolytic flux, in the reperfused heart. PMID- 8341000 TI - Relationship between pressure-rate product and myocardial oxygen consumption of normal and hypertrophic right ventricles in open-chest dogs. AB - There are few reports on the relationship between right ventricular performance and its myocardial oxygen consumption (RVMVO2). The present study was conducted to investigate the relationship between RVMVO2 and the mechanical performance of normal and hypertrophic right ventricles in open-chest dogs. Right ventricular hypertrophy (RVH) was induced by producing chronic right ventricular pressure overload by banding the pulmonary arteries of 8 puppies for 6 months. The experiment was performed under basal conditions and after increasing the RVMVO2 in the eight dogs with RVH as well as in 20 normal dogs. The RVMVO2 showed significant positive relationships with right coronary (RCA) flow, right ventricular systolic pressure, and right ventricular pressure-rate product (PRP) in both the normal right ventricle and RVH hearts. However, the slope between the PRP and RVMVO2 was significantly steeper in the normal right ventricle (RV) than in the hypertrophic RV. When the PRP was normalized for the thickness of the right ventricular free wall, the slope of the two regression lines merged into a single line of fit. These results suggest that the pressure-rate product can be used to predict myocardial oxygen demand not only in the normal RV but also in well-compensated, hypertrophic RV. Isoproterenol induced smaller increases in cardiac output in the dogs with RVH than in those with normal RV. It also appears that the cardiac output of the hypertrophic RV is less sensitive to beta adrenoceptor stimulation than that of the normal RV. PMID- 8341001 TI - The relationship between early afterdepolarization and the occurrence of torsades de pointes--an in vivo canine model study. AB - The relationship between early afterdepolarization (EAD) and the occurrence of torsades de pointes (TdP) was studied in a canine model. Twelve dogs of both sexes, weighing 9.9-16 Kg, were studied. After reducing the concentration of serum potassium to 3.0-4.0 mEq/l, by administration of calcium polystyrene sulfonate at 15-20 g/day for 1 or 2 weeks, a 6F electrode catheter was introduced via the femoral vein and positioned at the atrioventricular (AV) junction. Complete AV block was produced by catheter ablation using a high frequency current. A Franz 6F catheter was introduced into the right ventricle to record monophasic action potentials (MAPs) using the contact electrode technique. After a stable recording of the MAPs was achieved, cesium chloride (CsCl; 1 mM/Kg) was administered as an intravenous bolus over 15 sec. The MAPs and electrocardiogram (ECG) changes were simultaneously recorded for 30 min after the administration of CsCl. The administration was repeated several times at intervals 30 min. Sustained or non-sustained ventricular tachycardia was produced in all dogs. EAD appeared in 8 of 12 dogs. When EAD developed sufficiently high amplitude, ventricular premature beats occurred near the peak of EAD and TdP was induced in 3 of 8 EAD-positive dogs. TdP was not induced in EAD-negative dogs. Although TdP was comparatively difficult to induce, EAD-triggered activity was suggested to be one of the necessary conditions for TdP, because TdP occurred only when EAD reached a sufficiently high amplitude to produce ventricular premature beats. PMID- 8341002 TI - Beneficial effect of the addition of nitroglycerin to the cardioplegic solution on the cold-stored reperfused isolated rat heart. AB - We discuss here the effect of the addition of trinitroglycerin to the cardioplegic solution on the isolated rat heart after eight hours of storage. This effect was evaluated by measuring cardiac function as well as myocardial calcium and enzymes. Male Wistar rats were divided into three groups based on the concentration of trinitroglycerine in the cardioplegic solution. In the control group, the fluid used was a crystalloid cardioplegic solution (K+ 25 mEq/L) without trinitroglycerin and for groups I and II, trinitroglycerin was added at concentrations of 2 micrograms/ml and 5 micrograms/ml, respectively. All hearts were arrested with the cardioplegic solution at 4 degrees C and then immersed for eight hours in Euro-Collins' solution at 4 degrees C. The postperfusion coronary flow showed higher rates for groups I and II than for the control group (p < 0.05), while the difference between groups I and II was not significant. In group I, the total concentrations of creatine kinase-MB, lactate and malondialdehyde after reperfusion showed the lowest levels; this group also had the lowest content of myocardial calcium. These results indicate that the addition of nitroglycerin, especially at a concentration of 2 micrograms/ml, to the cardioplegic solution elicits better cardiac function for immersed rat heart. PMID- 8341003 TI - Ischemic heart disease showing unusual angiographic findings. AB - Atherosclerotic lesions usually occur in the proximal and middle portion of the coronary arteries. Multiple obstructive lesions appearing only in the peripheral branches without lesions in the proximal or distal portion have not been reported. We encountered a patient with ischemic heart disease showing multiple obstruction in the peripheral branches of the right and left coronary arteries without significant stenotic lesions in the proximal or middle portion. This 49 year-old male was admitted to Yamada Red Cross Hospital due to angina pectoris. Coronary risk factors for him included hypertension, abnormal glucose tolerance, smoking habit, and obesity. Laboratory studies showed a complete blood count and normal blood chemistries, as well as thromboplastin and prothrombin times. Coronary angiography showed multiple obstruction or marked stenosis in the distal portion and peripheral branches; there was no stenosis in the proximal and middle portions. Left ventriculography showed severe hypokinesis in the diaphragmatic segment. Biopsy of the left ventricular endocardium showed interstitial fibrosis but showed no abnormalities in the myocardial fibers or cell infiltration to perivascular areas and vascular walls. Coronary angiography after two months showed multiple lesions, as previously observed. Although ischemic heart disease is caused by various types of vasculitis, embolism, coronary spasm, and fibromuscular dysplasia, in this patient, there were no findings suggestive of causes other than atherosclerosis. This case is interesting in terms of rare angiographic findings and its cause. PMID- 8341004 TI - Massive myocardial calcification of right and left ventricles following acute myocarditis complicated with rhabdomyolysis-induced acute renal failure. AB - A 26-year-old man was admitted with a high fever, oliguria, skeletal muscle weakness, and cardiogenic shock which led to a diagnosis of acute myocarditis and acute rhabdomyolysis. During treatment with hemodialysis and calcium supplementation, because of severe hypocalcemia, a massive calcification of both right and left ventricular myocardium gradually became apparent with repeated computed tomographic (CT) examinations. Technetium-99m scannings more clearly delineated the markedly accumulated calcium in the myocardium, while significant activity was not detected in other soft tissues. Histopathological examinations by myocardial biopsy revealed a large amount of fibrosis and calcium deposits, and serial CT scans showed a gradual regression of the calcium deposition, suggesting that this rare form of massive dystrophic calcification may parallel changes in the severity of myocarditis, and may be associated with abnormalities in calcium metabolism secondary to rhabdomyolysis-induced acute renal failure. PMID- 8341005 TI - A case of dilated cardiomyopathy manifested by exercise-induced left bundle branch block. AB - We report an extremely rare case of dilated cardiomyopathy manifested by exercise induced left bundle branch block. A 63-year-old female came to our hospital because supraventricular arrhythmia had been detected at a check-up. A treadmill exercise test induced left bundle branch block. However, chest X-ray and echocardiography revealed no abnormal finding. Two years later, the patient experienced exertional dyspnea. A chest X-ray examination showed cardiomegaly, and echocardiography showed a moderate impairment of left ventricular function with left ventricular dilatation. The diagnosis of dilated cardiomyopathy was made by left ventricular myocardial biopsy. No previous cases have initially shown exercise-induced left bundle branch block which was followed by left ventricular dysfunction due to dilated cardiomyopathy. Careful long-term observation of the clinical course is necessary in patients with exercise-induced left bundle branch block which shows no significant underlying disease. PMID- 8341006 TI - Effect of transforming growth factor-beta on extracellular matrix production by cultured rat mesangial cells. AB - The effects of transforming growth factor-beta (TGF-beta) on the protein synthesis and gene expression of collagen I (CI), III (CIII), IV (CIV) and laminin (LM) in cultured rat mesangial cells (MCs) were examined to determine whether or not TGF-beta could modulate the formation of extracellular matrix (ECM) constituents, employing immunocytochemistry, enzyme-linked immunoadsorbent assay (ELISA) and Northern blotting. Although TGF-beta did not modulate MC proliferation, it induced slight enhancement of immunoperoxidase staining for CIV in the cytoplasm. ELISA demonstrated a significant increase in the amounts of CIV and LM, a tendency for CIII to increase, and a significantly lower amount of CI at 4 days after TGF-beta administration. Northern blotting showed that the mRNA expression displayed different patterns among the 4 matrix components during a 24 hr period. These findings suggest that a single growth factor, TGF-beta, in vitro modulates the synthesis of individual ECM constituents in MCs differently at the level of both genetic expression and protein production. The specific effects of TGF-beta on the increase in amounts of CIV and LM indicate that TGF-beta may contribute to glomerular remodeling and ECM accumulation in various kinds of glomerular injuries. PMID- 8341007 TI - Inhibitory effects of crude drug components on the proliferation of cultured human mesangial cells. AB - The effects of a component of an Oriental medicine and green tea plants utilized for the traditional beverage on the proliferation of mesangial cells were determined in terms of the 3H-thymidine uptake. When magnesium lithospermate B was added to the medium of the mesangial cell culture, it suppressed the proliferation of mesangial cells at a concentration of 50 micrograms/ml. The 3H thymidine uptake began to display an inhibitory action from the 6.25 micrograms/ml (-)-epicatechin 3-O-gallate, (-)-epigallocatechin 3-O-gallate or green tea tannin mixture, showing a more conspicuous inhibition at 50 micrograms/ml that did the magnesium lithospermate B at the corresponding concentration. In particular, (-)-epigallocatechin 3-O-gallate, the predominant component of the green tea tannin mixture, exerted an inhibitory effect at a relatively low concentration. PMID- 8341008 TI - Dilazep prevents glomerulosclerosis in accelerated Masugi nephritis in the rat. AB - The effects of Dilazep on immunologically induced glomerular injuries were examined. Accelerated Masugi nephritis in rats produced glomerulosclerosis with proteinuria following administration of a single dose of nephrotoxic serum (NTS). When 5 mg/kg/day of Dilazep had been administered prior to the NTS injection, the proteinuria was resolved rapidly after reaching a maximum level. The glomeruli 3 months later showed significant suppression of glomerulosclerosis and lesser adhesive lesions as compared to those in control rats with Masugi nephritis. On the other hand, when Dilazep was administered from 2 weeks after the injection of NTS, the rats displayed persistent proteinuria and glomerulosclerosis at similar levels to those in the Masugi group. Dilazep appears to exert some protective effects in the early stages of glomerular injuries induced by immunological mechanisms. PMID- 8341009 TI - Effect of magnesium lithospermate B on the renal and urinary kallikrein activities in rats with adenine-induced renal failure. AB - A study was conducted to examine the effect of magnesium lithospermate B on both the urinary and renal total and active kallikrein and prokallikrein in rats with adenine-induced renal failure. In rats given magnesium lithospermate B at a dose of 10 mg/kg body weight/day for 12 days, significant increases of urinary total and active kallikrein were associated with significant increases of urine volume and urinary total and active kallikrein were associated with significant increases of urine volume and urinary creatinine excretion. The renal total and active kallikrein levels were also significantly elevated by the treatment with magnesium lithospermate B. On day 24, the urinary excretion of total and active kallikrein and prokallikrein was significantly increased. Concomitantly, a significant increase in renal kallikrein (total, active and pro-) was found in the rats given magnesium lithospermate B. A significant relationship existed between the urinary creatinine and active kallikrein excretion. These results suggest that magnesium lithospermate B may stimulate the synthesis of kallikrein and/or conversion to active kallikrein, thus improving renal function. PMID- 8341010 TI - Effect of chronic central alpha-hANP administration on blood pressure, water and electrolyte balance in rats. AB - Relatively few studies have evaluated the chronic effects of atrial natriuretic polypeptide (ANP) administration into the central nervous system on peripheral cardiovascular and renal function under conditions of expanded extracellular fluid volume. The present investigation examined the effects of synthetic alpha human atrial natriuretic polypeptide (alpha-hANP) chronically infused into the cerebroventriculum of rats loaded with 0.9% saline. Measurements of the arterial blood pressure, water and electrolyte balances were carried out during a 4-day central ventricular infusion of alpha-hANP. Significant increases in daily urine volume and urinary sodium and chloride excretion were observed, but no changes of arterial blood pressure occurred. These results indicate that elevated levels of ANP in the CSF can influence sodium and water excretion, but do not appear to influence arterial pressure. PMID- 8341011 TI - A new murine model of autosomal recessive polycystic kidney disease. AB - We describe the renal cystic disease occurring in a new inbred strain of mice which developed as a spontaneous mutation in otherwise healthy Balb/c mice. The disease displays characteristics of an autosomal recessive polycystic kidney disease. Affected animals develop massive cystic enlargement of the kidneys and die of renal failure at the age of 4 weeks. During postnatal development, there is a gradual shift in site of the lesions. At birth, cystic dilations are localized almost exclusively in proximal tubular segments, whereas in the terminal stages of the disease, 80% of the cysts are localized in collecting tubular segments as defined by segment specific lectin binding. The composition of the basement membrane of the cystic tubular walls during postnatal development as analyzed by immunocytochemistry is essentially normal during the earliest stage of cyst formation. However, with disease progression, the cystic tubular basement membrane demonstrates a decreased immunoreactivity to anti-laminin and anti-entactin antibodies. This indicates a shift in cyst localization during disease progression in this model, and suggests that basement membrane abnormalities are not a primary feature of the early cyst formation and progressive enlargement. PMID- 8341012 TI - Page kidney with constrictive perinephritis. AB - We describe a case of Page kidney following an infectious urinoma complicated by a pyelolithotomy. The most characteristic finding was the fact that this case resulted from constrictive perinephritis, not from any usual etiology such as perirenal hematoma. Knowledge of the patient's medical history and split venous renin measurements were helpful in making a diagnosis. She had refractory hypertension during conservative medical therapy. Finally, a nephrectomy improved her hypertension. The value of venous renin sampling for reaching a diagnosis, and the medical and surgical therapeutic options are discussed. This report also reviews all previously described cases of Page kidney without hematomas. PMID- 8341013 TI - Investigation of the clinical value of assessing renal size on computed tomography in autosomal dominant polycystic kidney disease. AB - We examined relationship between serum creatinine concentration (Scr) and renal size on CT scans on 32 occasions in 25 patients with autosomal dominant polycystic kidney disease (ADPKD). As a result, a significant correlation was observed when the Scr was less than 5 mg/dl, as shown by the correlation coefficient (r) and P values of 0.803 and 0.0001, respectively. However, these values changed to 0.482 and 0.0093, respectively when 2 cases with Scr 6.2 and 6.4 mg/dl were included, and further changed to 0.005 and 0.9775 when an additional 4 cases with Scr 7.8, 9.9, 11.1 and 20.1 mg/dl were included. Renal size is therefore thought to be a useful parameter of renal function when the Scr is less than 5 mg/dl in ADPKD, but not when the Scr exceeds 6 mg/dl, and is regarded as useless for predicting the time at which dialysis would be required. PMID- 8341014 TI - Clinico-pathological studies of Amyloid-P component in human glomerulopathies. AB - Renal tissues from 171 patients with different glomerulopathies and 6 normal controls were examined by an immunofluorescent technique. Specimens were stained in particular with anti-Amyloid P (AP) antisera, and were also stained for immunoglobulins and complement. The intensity and distribution pattern of AP staining were studied. The AP staining revealed a faint/linear pattern in normal controls, and was granular and linear in pathological specimens. The distribution of AP was found to be mesangial, capillary and mesangiocapillary. According to the degree of AP intensity, the patients were divided into two groups: group I (56 patients) exhibiting a faint intensity as seen in the normal controls, and group II (115 patients) with a strong intensity. The histological findings and laboratory data were compared between the two groups as well as among patients with different diseases. The incidence of sclerotic lesions and the amount of proteinuria were significantly higher in group II than in group I. Increased amounts of AP deposition in different glomerular diseases thus appear to be related to a diminished renal function or glomerular damage. PMID- 8341015 TI - Plasma levels of superoxide dismutase and its isomers in patients with chronic renal disease. AB - To evaluate the significance of Cu,Zn-superoxide dismutase (SOD) in chronic renal disease, we evaluated the plasma SOD activity and analyzed the plasma Cu,Zn-SOD isomers employing gel column chromatography. The plasma SOD activity was determined as the biological activity using the nitrite method and the Cu,Zn-SOD concentration was assayed from the immunological activity using enzyme-linked immunosorbent assay (ELISA). The subjects comprised 185 patients with chronic glomerular disease and 20 hemodialysis patients. Plasma from 170 healthy persons was employed as a control. Both the plasma biological activity and plasma level of Cu,Zn-SOD determined by ELISA were elevated in patients with chronic glomerular disease. In hemodialysis patients, a marked increase in Cu,Zn-SOD level (ELISA) was noted in comparison with the increase in SOD biological activities. Gel column chromatography demonstrated a marked increase in Cu,Zn-SOD monomer which was enzymatically inactive. From these results, we conclude that a marked elevation of the plasma level of Cu,Zn-SOD in hemodialysis patients was caused by an increase in the enzymatically inactive Cu,Zn-SOD monomer. PMID- 8341016 TI - Oral 1,25(OH)2D3 pulse therapy for the treatment of secondary hyperparathyroidism. AB - We examined the effect of oral 1,25(OH)2D3 pulse therapy in hemodialyzed patients with secondary hyperparthyroidism (2 degrees HPT). Prescription of 6.0 micrograms 1,25(OH)2D3 once a week combined with calcium carbonate as a phosphate binder during the last 5 days a week for 12 weeks resulted in improvement of mild to moderate 2 degrees HPT despite no significant differences in serum total calcium and phosphate concentration. In addition, the effect was greater in cases with mild 2 degrees HPT. A single administration of 6 micrograms 1,25(OH)2D3 reduced the parathyroid hormone concentration in patients with mild 2 degrees HPT or with a short duration of hemodialysis. Tmax of the serum 1,25(OH)2D3 after single administration of 6.0 micrograms 1,25(OH)2D3 was individually different (range, 0.4-20.9 hrs). It is recommended that early employment of oral 1,25(OH)2D3 pulse therapy be undertaken once a week combined with prescription of calcium salt as a phosphate binder during the last 5 days a week for the treatment of 2 degrees HPT refractory to conventional therapy, since there is no risk of aluminum accumulation with satisfactory control of the serum total calcium and phosphate concentration. PMID- 8341017 TI - Autosomal dominant polycystic kidney disease in a child diagnosed by ultrasonography. AB - A 10-year-old boy with a chief complaint of nocturnal enuresis was identified as having three cysts in each kidney on ultrasonographic examination. These findings together with a positive family history for renal failure prompted us to examine his father ultrasonographically on the same day, resulting in the identification of multiple large cysts in both kidneys. These observations supported a diagnosis of autosomal dominant polycystic kidney disease. Enhanced X-ray CT demonstrated more sensitively the presence of renal cysts in the boy. He had a normal urinary concentrating ability and no other abnormalities except for mild hypertension, which was successfully treated only by salt restriction. Ultrasonography thus appears to be a valuable tool for diagnosing polycystic kidney diseases. PMID- 8341018 TI - A case of minimal change nephrotic syndrome associated with acute renal failure after excessive exercise. AB - A case of minimal change nephrotic syndrome associated with acute oliguric renal failure after exercise is reported. Renal function returned to normal after the patient underwent hemodialysis, and the nephrotic state was improved by administration of prednisolone. Adequate supportive management of the renal failure and early administration of corticosteroids for nephrotic syndrome are important therapeutic procedures in such a situation. PMID- 8341019 TI - Inhibitory effect of FUT-175 on complement activation and its application for glomerulonephritis with hypocomplementemia. AB - FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethane-sulphonate), a potent serine protease inhibitor, has been reported to inhibit complement activity in vitro, and especially the classical complement pathway effectively. In the present study, we examined the inhibitory effect of FUT-175 on the classical complement pathway components by hemolytic assay using purified human complement components. As a result, 50% inhibition of the C1 protease activity for classical C3 convertase formation and for C2 was obtained with 3.0 x 10(-8) M and 7.0 x 10( 8) M of FUT-175, respectively. FUT-175 did not inhibit the C2 protease activity at all. We then administered FUT-175 to 5 glomerulonephritic patients with hypocomplementemia and proteinuria in order to assess the clinical effectiveness of this drug. When FUT-175 was administered intravenously and continuously at a rate of 0.1 to 0.2 mg/kg/hr for 2 weeks, the urinary protein excretion decreased significantly from 2.9 +/- 0.8 to 1.4 +/- 0.5 g/day (P < 0.025). In these patients, some of the serum complement markers (serum C3, C4 level and the hemolytic activity via the classical complement pathway (CH50)) were increased after FUT-175 administration. The above findings suggests that FUT-175 can exert beneficial effects on glomerulonephritis with hypocomplementemia by inhibiting complement activation. PMID- 8341020 TI - A clinico-pathological study on progress factors in lupus nephritis. AB - The prognosis of lupus nephritis was investigated in 147 patients who underwent renal biopsy, in an attempt to elucidate the progress factors of this disease clinico-pathologically. Twenty-two patients received a follow-up biopsy and were observed for time-related histopathological changes. At the first examination, only the serum creatinine and mean blood pressure were correlated with prognosis. The anti-DNA antibody and serum complement titer measured at the same time did not correlate with prognosis, and neither showed a significant improvement in the poor prognosis group. Profuse proteinuria tended to last longer in the poor prognosis group. The renal biopsy findings were found to correlate with prognosis. The prognosis was especially poor in patients exhibiting marked mesangial cell proliferation, glomerulosclerosis and interstitial lesions. PMID- 8341021 TI - Hypersensitivity to heparin; a case report. AB - Hypersensitivity reactions to heparin are very rare. A generalized hypersensitivity reaction including as fever and skin rash to a porcine- and bovine-derived heparin preparation was observed in a hemodialysis patient due to the nephrotic syndrome. The patient revealed peripheral eosinophilia and normal serum IgE. The results of a drug lymphocyte stimulating test on heparin were positive. Following prednisolone administration and infusion of nafamostat mesilate as anticoagulant therapy during hemodialysis, the high fever and generalized urticaria disappeared. Caution is required when conducting heparin therapy on hemodialysis patients. PMID- 8341022 TI - A case complicated with SLE during maintenance hemodialysis. AB - A 40-year-old woman suffered from toxemia of pregnancy in 1977 and was admitted to hospital. Thereafter, she developed nephrotic syndrome, underwent a renal biopsy, and a diagnosis of membranoproliferative glomerulonephritis (MPGN) was made. She received steroid therapy, immunosuppressive drug and anticoagulant therapy, and recovered sufficiently to be discharged from hospital in April, 1979. During subsequent ambulatory treatment at our outpatient department, her renal function deteriorated gradually, and maintenance hemodialysis was started from June, 1990. In July, 1991, she was admitted to our hospital with pleurisy and pericarditis. There was no improvement despite antibiotic treatments. Laboratory data revealed leukopenia and lymphopenia. Under suspicion of systemic lupus erythematosus (SLE), relevant tests were carried out. Immunological abnormalities such as positive LE cells and the presence of various autoantibodies, together with clinical signs of hypersensitivity to sunlight, stomatitis and serositis, satisfied the diagnostic criteria of the ARA and a diagnosis of SLE was made. This case did not exhibit any clinical or serological abnormalities except for the renal disorder for a 10-year period after the histological diagnosis of MPGN, but was eventually diagnosed as SLE as a result of the manifestation of SLE symptoms for the first time after one year of maintenance hemodialysis. Immunological abnormalities and SLE during maintenance hemodialysis are discussed in relation to other reports. PMID- 8341023 TI - Improvement of ischemic myocardial dysfunction by nisoldipine in relation to its coronary vasodilating action. AB - We examined the cardioprotective effect of nisoldipine against myocardial dysfunction during ischemia and reperfusion in comparison with those of diltiazem and nifedipine in rabbit hearts perfused at constant pressure. These calcium antagonists were administered to the hearts before 60 min of ischemia. They inhibited the increase of end-diastolic pressure during ischemia in a dose dependent manner. Diltiazem at 1.0 microM, nifedipine at 3.0 microM and nisoldipine at 0.01 microM produced the maximal cardioprotective effect. Nisoldipine had a beneficial effect with less negative inotropic effect than those of diltiazem and nifedipine and it produced a significant increase of coronary flow during reperfusion. When the vascular component was eliminated under constant flow perfusion, nisoldipine also showed the cardioprotective effect. Nisoldipine did not produce any beneficial effect without the inhibition of the increase in end-diastolic pressure during ischemia nor did it do so without the increase of reperfusion flow. Therefore, the nisoldipine-increased coronary flow during reperfusion as well as the inhibition of ischemic contracture by nisoldipine seems to play a crucial role in improving the myocardial dysfunction of ischemic-reperfused hearts. PMID- 8341024 TI - G protein beta gamma-subunits inhibit purified adenylate cyclase independent of the activation by Ca2+ and calmodulin. AB - Adenylate cyclase purified by affinity chromatography was activated about 2.5 fold in a Ca(2+)- and calmodulin-dependent fashion. G protein beta gamma subunits, an inhibitor in the receptor-mediated inhibition of adenylate cyclase, inhibited the purified cyclase by more than 80%. The extent of beta gamma-induced inhibition was not affected by the activation with Ca2+ and calmodulin. Moreover, the prior addition of the beta gamma-subunits to the cyclase did not prevent the subsequent activation of the enzyme by Ca2+ and calmodulin. We conclude that the beta gamma-subunits inhibit adenylate cyclase activity in a calmodulin independent mode. PMID- 8341025 TI - Effects of heparin on the inhibitory activities of human urinary trypsin inhibitor (ulinastatin) on trypsin, chymotrypsin and leukocyte elastase. AB - Effects of heparin on the inhibitory activities of human urinary trypsin inhibitor (ulinastatin) on trypsin, chymotrypsin and leukocyte elastase were studied. Heparin per se neither influenced the enzymatic activities nor changed the mode of inhibition of ulinastatin on the enzymes. In the presence of heparin, inhibitory effects of ulinastatin on trypsin were enhanced, whereas its effects on chymotrypsin and elastase were attenuated. These results suggest that the two functional domains in ulinastatin are differently affected by heparin. PMID- 8341026 TI - Effect of NC-1300-O-3 on healing of acetic acid-induced gastric ulcers in rats. AB - We examined the effect of NC-1300-O-3 on the healing of acetic acid-induced gastric ulcers in male Donryu rats. NC-1300-O-3, administered orally once daily for 2, 4 or 8 weeks after ulceration, significantly accelerated the spontaneous healing of both fresh and unhealed ulcers (induced by pretreatment with indomethacin). The delay in ulcer healing caused by indomethacin was markedly prevented by concurrent administration of NC-1300-O-3 once daily for 4 weeks in a dose-related manner. A bolus administration of NC-1300-O-3 to rats with 5-day-old ulcers potently and persistently (> 48 hr) inhibited both the basal and histamine stimulated gastric secretion. However, the potency and duration of the anti secretory activity of the compound, with or without indomethacin, gradually decreased with the period of treatment. After an 8-week treatment with NC-1300-O 3 alone, the volume of the gastric contents was markedly increased, resulting in an increased acid output. Administration of the compound together with indomethacin for 8 weeks resulted in a significant increase in the volume, no change in acid output and a significant increase in the pH. The spontaneous or delayed healing of gastric ulcers induced 4 weeks after pretreatment with NC-1300 O-3 was also significantly enhanced or prevented with NC-1300-O-3, with a weakened antisecretory activity. Therefore, NC-1300-O-3 seems to promote ulcer healing or prevents delayed healing by its potential antisecretory and/or ulcer healing activities. PMID- 8341027 TI - Streptozocin-diabetes modifies acetylcholine release from mouse phrenic nerve terminal and presynaptic sensitivity to succinylcholine. AB - Acetylcholine (ACh) release from the motor nerve terminal in the streptozocin induced diabetic state was studied in mouse phrenic nerve-diaphragm muscle preparations. Electrically evoked release of 3H-ACh from the preparation preloaded with 3H-choline was measured during two consecutive periods of stimulation (S1 and S2). In diabetic mice, the amount of 3H-ACh release during S2 was decreased, and the evoked ACh release declined more steeply with successive stimulation periods than in normal ddY mice. The decrease in release was restored when the presynaptic autoreceptors were stimulated by accumulating ACh under the irreversible inhibition of junctional cholinesterase by methanesulfonyl fluoride. This effect was abolished by the administration of (+)-tubocurarine (5 microM). In diabetic mice, the biphasic (acceleration and suppression) effect by succinylcholine on evoked ACh release was caused at 3- to 10-fold lower concentrations than in normal mice. The degree of enhancement of resting 3H overflow by succinylcholine (10 and 30 microM) was greater in the diabetic state. These results indicated that in the diabetic state, the decrease in evoked ACh release interferes with its presynaptic action on inducing further release (positive feedback modulation) via the presynaptic nicotinic ACh receptor (n AChR). The presynaptic hypersensitivity to succinylcholine may be due to the augmentation of presynaptic n-AChR sensitivity caused by the reduction of evoked ACh release in the diabetic state. PMID- 8341028 TI - Mechanisms of the hypolipidemic effect of NIP-200 in rats. AB - We studied the mechanisms of hypolipidemic effects of NIP-200 (3,5-dimethyl-4,6 diphenyltetrahydro-2H-1,3,5-thiadiazine- 2-thione), a potent hypolipidemic compound, in cholesterol biosynthesis in the liver, cholesterol absorption in small intestine, and cholesterol catabolism and excretion in rats. NIP-200 did not reduce cholesterol biosynthesis and had no effects on cholesterol absorption in the small intestine. In the cholesterol catabolism and excretion, NIP-200 induced increases in cholesterol and bile acids levels in the bile and acidic steroids in the feces, and it enhanced cholesterol 7 alpha-hydroxylase activity in the liver. These results suggest that NIP-200 increases the synthesis of bile acids as a result of the activation of cholesterol 7 alpha-hydroxylase, the rate limiting enzyme in the conversion of cholesterol to bile acids. Therefore, it is considered that one of the probable mechanisms of the serum total cholesterol lowering action of NIP-200 involves the enhancement of catabolism and excretion of cholesterol in the liver. PMID- 8341029 TI - Organic hydroperoxide-induced activation of liver microsomal glutathione S transferase of rats in vitro. AB - The effect of t-butyl hydroperoxide (t-BuOOH), cumene hydroperoxide (CuOOH) or linoleic acid hydroperoxide (linoleic-OOH) on liver microsomal glutathione S transferase of rats was studied in vitro. When microsomes were incubated with either 100 microM t-BuOOH or 25 microM CuOOH, glutathione S-transferase activity was increased 1.5-fold; activity was further increased to 2.2-fold in the presence of small amounts of glutathione. The same amounts of dithiothreitol or cysteine did not enhance the t-BuOOH or CuOOH-induced increase in transferase activity. The transferase activity was also increased 1.4-fold by 10 microM linoleic-OOH plus 1 microM glutathione. The increase in microsomal glutathione S transferase activity after treatment of microsomes with t-BuOOH in the presence of glutathione was completely reversed by addition of dithiothreitol, whereas the activation of the transferase caused by t-BuOOH in the absence of glutathione was not reversed. Although microsomal glutathione S-transferase also possesses glutathione peroxidase activity, only transferase activity was increased by t BuOOH in either the presence or absence of glutathione. These data indicate that microsomal glutathione S-transferase is activated by organic hydroperoxides in either the absence or presence of small amounts of glutathione, suggesting an activation of the transferase by thiol oxidation of the cysteine residue. PMID- 8341030 TI - Pharmacological properties of blood pressure and heart rate control in suncus. AB - Blood pressure and heart rate and responses to various physiological substances in suncus were characterized and compared with those in mice. The blood pressures of the two species were similar, but the heart rate of suncus (about 400 beat/min) was significantly lower than that of mice. Norepinephrine increased the blood pressure but decreased the heart rate in suncus. The latter was blocked by cervical vagotomy. Sensitivities to acetylcholine and isoproterenol were lower in suncus. These results suggest that regulation of blood pressure and heart rate in suncus is very unique and different from the well-defined system of the rodents. PMID- 8341031 TI - Effects of OM-853, a novel indolonaphthyridine derivative, on behavioral responses in the forced swim test in rats. AB - Effects of OM-853 on behavioral responses in the forced swim test were studied. OM-853 significantly reduced the duration of immobility without any change in the exploratory activity. Imipramine also reduced the duration of immobility, but idebenone did not. On the other hand, vinpocetine enhanced the duration with a suppressive effect on ambulation. The anti-immobility effect of OM-853 was reversed by pretreatment with haloperidol. These results demonstrate that the effect of OM-853 on the swim test is different from that of idebenone and vinpocetine. Furthermore, the present results suggest that OM-853 may exert its anti-immobility activity through facilitated transmission of the dopaminergic and/or adrenergic systems. PMID- 8341032 TI - The self-locking Balgrist hip socket for cementless fixation: biomechanical principles and clinical results. AB - The Balgrist hip socket, initially made entirely of HDPE (high molecular weight polyethylene), now made of outer titanium alloy shell that faces the bone of the acetabulum has been in clinical use for 10 years. The purpose of this presentation is to illustrate the biomechanical principles that have governed this unique design and to present the clinical results that we have obtained until the end of 1991 with 717 implants. From 1982 to 1987 Balgrist HDPE sockets had been implanted for 346 hips, from 1984 to 1991 Balgrist Titanium alloy sockets have been implanted for 371 hips. The number of revision are 55 of 717 hips. 48 hips out of 55 were with Balgrist HDPE sockets. On the contrary, only 7 hips were with Balgrist titanium socket. The greatest benefit of Balgrist Titanium socket is the excellent mechanical lock with subchondral bone of the acetabulum. PMID- 8341033 TI - Alpha-adrenergic blockade with phenoxybenzamine enhances cerebrovascular CO2 reactivity. AB - The influence of sympathetic nervous activity on cerebral circulation and cerebrovascular CO2 reactivity was investigated by an alpha-adrenergic blockade with phenoxybenzamine (PBZ). Cerebral oxygen and carbon dioxide tension (BrPo2, BrPco2) and arterial blood pressure were continuously recorded before, during and after intracarotid infusion of 5 mg/kg of PBZ. The effects of 5% CO2 inhalation were measured before and after the infusion of PBZ. Following the intracarotid infusion of PBZ, BrPo2 and BrPco2 did not change significantly. After the alpha adrenergic blockade the degree of the increase in BrPo2 during 5% CO2 inhalation was significantly enhanced. The increase in the cerebrovascular CO2 reactivity produced by low dose PBZ suggests that the sympathetic nervous system modifies cerebrovascular CO2 reactivity. PMID- 8341034 TI - Effect of clonidine on the cerebrovascular system in cats. AB - The effects of clonidine, a potent alpha 2 adrenergic agonist and an imidazole/imidazoline receptor agonist, were examined in the cat cerebrovascular system, measuring cerebral oxygen and carbon dioxide tension (BrPo2, BrPco2) and arterial blood pressure. Intracarotid injection of clonidine (2 micrograms/kg) produced a gradual decrease in systemic blood pressure without initial hypertension, while BrPo2 decreased slightly but significantly. Before and after intracarotid administration of clonidine, cerebrovascular reactivity to carbon dioxide was estimated by changes in BrPo2 and BrPco2 during and after 3 min inhalation of 5% CO2. Clonidine significantly enhanced cerebrovascular reactivity to carbon dioxide. The data suggest that the alpha 2-adrenoceptor and/or imidazoline receptor play an important role in the regulation of cerebral circulation. PMID- 8341035 TI - The dramatic change from empirical to scientific technology in medicine: computerized imaging, communications and holography. AB - Perhaps the single most important element in the rapid development of contemporary diagnostic imaging is simply its feasibility that results from the deliberate use of complicated, but powerful, mathematical formulation. Implemented with various types of computers, today mostly digital, in such applications at CT (computerized tomography), MRI (magnetic resonance imaging) and others, the underlying principles of the 3-D (three-dimensional) image recording and reconstruction can all be traced back to the principles of "holography". Further improvements in image communications and processing, for example in view of robotized "Imaging-guided Stereotactic Diagnosis and Treatment" in high-field MRI is likely to result from suitable use of "Fuzzy Logic". PMID- 8341036 TI - A female infant with DiGeorge syndrome. PMID- 8341037 TI - [A study of knowledge, attitude and health behavior toward tuberculosis among non immigrant Korean people in Japan]. AB - Knowledge, attitude and health behavior toward tuberculosis among Non-immigrant Korean people in Japan was researched by using questionnaire because of increasing the number of the tuberculosis patients among those group. The Korean member of protestant churches in Tokyo were subjects for the survey. Immigrant Korean people and their descendants were excluded. The questionnaire form was written in Korean language under the guidance of native Korean tuberculosis specialists. Proportion of Response was 53.1%, or 251 among 473 from 10th January to 30th June in 1992. The knowledge of tuberculosis among them was revealed to be higher than among ordinary native Korean people. It was different statistically by generation, namely, younger subjects aged less than 40 years old tended to answer that tuberculosis was a minor illness. The mass screening system in Japan was well known by the subjects, as shown by the fact that 72.4% of them answered that they knew about it. But only 56.6% of them replied that they actually took the mass screening. The source of its information was different statistically by sex, occupation, and generation. As for their health behavior, nearly two third (63.7%) of them visited the hospital or dispensary quickly when they fell sick. A small number of them answered that they could not visit a doctor because of their problems with the Japanese language. More than 80% of them possessed a National Health Insurance certificate. This proportion varied according to the period of stay in Japan. That is to say, The group which stayed in Japan less than one year was significantly the lowest because they were limited in their ability to enter National Health Insurance. PMID- 8341038 TI - [INH preventive therapy in Chiba Prefecture--before and after the renewal of the guideline]. AB - To prescribe or withhold isoniazid (INH) for tuberculin skin test reactors is a difficult question in our country where BCG coverage rate is high. The guideline for INH preventive therapy renewed in 1989 says that the decision should be made according to the maximum erythema diameter of tuberculin skin test considering if the patient is a contact or non-contact, BCG vaccinated or non-vaccinated. In addition, evidence of recent infection is also important. We reported the INH preventive therapy in Chiba prefecture before and after the renewal of the guideline. There were 347 cases before and 571 after the renewal of the guideline. The cases of which maximum erythema diameter were coincided with the recommendation of the guideline were 50.2% and 78.6% respectively. Close contacts of infectious tuberculosis, i.e. cases founded out in extraordinary health examination and household contacts examination, showed high coincidence rate. On the contrary, tuberculin-positive infants found in routine health examination, who are neither contacts nor BCG vaccinated, showed low coincidence rate and seemed to be administered INH by their home- or school-doctors' own standards. These trends were the same before and after the renewal of the guideline. PMID- 8341039 TI - [HIV-infection, AIDS and BCG vaccination]. AB - Bacille Calmette-Guerin (BCG) has been widely used as a safe and effective vaccine for the protection of tuberculosis, but recent epidemic of human immunodeficiency virus (HIV) infection evoked serious concerns about the safety of BCG when vaccinated to HIV-infected persons: that is, because BCG is a live, though avirulent, bacterial vaccine, it might grow in immuncompromised host and might cause dissemination and/or exacerbated local adverse reactions. In fact, during the decade since the first report on AIDS in 1981, several reports were published on the adverse reactions, systemic or local, induced by BCG in HIV infected persons. In this paper, the present author attempted to review such reports as comprehensively as possible. From critical examinations of the literatures, it was concluded that: 1) None of the reports dealing with dissemination of BCG provided satisfactorily enough evidence to identify the isolated mycobacteria as Mycobacterium bovis BCG. In some cases, infection with wild strain of M. bovis, instead of BCG, should be considered as more plausible pathogen. Especially, two reports, which suggested the late reactivation and dissemination of BCG vaccinated 30 years ago, could not be accepted without more detailed description of the procedures and results of the identification tests. In some cases, application of BCG were considered to be inappropriate. According to the present author's judgement, when BCG was applied appropriately as an anti tuberculosis vaccine, generalized infections were most plausively induced by BCG only in 4 cases during this decade. 2) As for the local adverse reactions, many reported cases of outbreak of local adverse reactions, such as local ulceration and supprative lymphadenitis, were not related to HIV-infection at all, but were due to the usage of an inferior vaccine produced by a specified manufacturer (Pasteur Institute, Paris). Conclusion was that BCG could be safely vaccinated to children born from HIV-seropositive mothers, even if children themselves were also infected with HIV, so long as BCG vaccine of good quality was used. 3) Positive conversion rate of post-vaccination tuberculin skin-test seemed to be lower in HIV-infected children than in children born from HIV-seronegative mothers. But, about 30% of the HIV-infected children converted to tuberculin positive after BCG vaccination suggesting the effectiveness of the vaccination for the considerable fraction of the babies at the highest risk of tuberculosis infection. Positive conversion rate was much higher in HIV-noninfected children born from HIV-seropositive mothers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341040 TI - Chronic neuropsychological impairment resulting from disulfiram overdose. AB - The present case study examines the sequelae of disulfiram overdose and resulting chronic organic brain syndrome, with a 45-year-old, white, male alcoholic. Previous reports have discussed acute organic brain syndromes that are reversed after discontinuance of the drug. This particular case, however, resulted in significant cerebral impairment that was irreversible. Full neuropsychological testing which describes the extent of these neurologic deficits is presented, along with some possible reasons for these chronic sequelae. PMID- 8341041 TI - Attenuated cortisol response to biobehavioral stressors in sober alcoholics. AB - Sober alcoholics show an attenuated hormonal response to pharmacological agents that normally stimulate the hypothalamic-pituitary-adrenocortical (HPAC) axis. To determine if this same result would be found using biobehavioral stressors, 52 detoxified (mean = 32 days) male alcoholics and 30 male nonalcoholic controls were given two moderately aversive tasks (mental arithmetic and cold pressor test). Three samples of blood were drawn during a 2.5-hour prestressor baseline, a fourth immediately following the stressors and a fifth, 20 minutes later. At each of these times, subjects were asked to report their degree of distress. Serum cortisol concentrations did not differ between groups at baseline or immediately following the stressors, but 20 minutes later alcoholics had significantly lower concentrations than controls. The groups did not differ on their degree of self-reported distress in response to the stressors. Thus, while alcoholics appeared to affectively experience stressful events in a manner similar to that of controls, they had an attenuated cortisol response. A possible pathophysiological mechanism for this dysregulation is discussed in addition to the potential existence of a premorbid condition. PMID- 8341042 TI - Alcohol and aggression: a social information processing analysis. AB - The present study represents a preliminary exploration of the effects of alcohol on aggression (a hypothetical response to a videotaped provocation), using a social information processing model. Subjects were male social drinkers who received either a control beverage (ginger ale), placebo, .45 g/kg alcohol or .85 g/kg alcohol. Subjects observed a series of videotaped scenes of potential conflict occurring in the lounge of a college dormitory. In these scenes, an intruder switched the channel on a television set without asking the person watching for permission. The four groups were similar in their ability to encode and interpret social cues. Subjects in the 0.85 g/kg group were less able to generate competent (nonaggressive) solutions and were less likely than controls to select adaptive (nonaggressive) solutions. Subjects in the .85 g/kg group were more likely than control subjects to respond aggressively after being frustrated by the intruder's negative reaction to the initial attempt to resolve the conflict. PMID- 8341043 TI - Auditory event-related potentials in children at high risk for alcoholism. AB - To determine if P300 and other event-related potentials (ERP) could serve as markers for risk of developing alcoholism, two groups of children (8-18 years old) were tested. The high-risk (HR) group consisted of 51 children with an average of 4.1 first- and second-degree relatives who were alcoholic. The low risk group (LR) consisted of 42 children who had no first- or second-degree relatives who were alcoholic or met criteria for DSM-III Axis I psychopathology. Auditory stimuli varying in conditional probability were presented during a silent counting task, and during a choice reaction task. P300 amplitude was smaller in high-risk than low-risk children. When grouped according to gender and developmental status (8-12 and 13-18 year olds), P300 showed the greatest reduction for the older high-risk males compared to low-risk males. In addition, a previous finding was replicated: the prolonged centro-frontal negativity (232 352 msec), which decreased with age in low-risk children, showed significantly less reduction for high-risk children. Risk status was not related to either amplitudes of the N100 and P200 components of the ERP, or to latencies of any components. Decreases in P300 amplitude and delayed reduction of anterior negativity appear related to developmental processes in high-risk children. PMID- 8341044 TI - A retrospective measure of childhood behavior problems and its use in predicting adolescent problem behaviors. AB - Confirmatory factor analysis was used to support the dimensional structure of a four-factor retrospective measure of childhood behavior problems with a large, nonclinical adolescent sample. Acceptable levels of internal consistency and low to-moderate levels of parent-adolescent interrater agreement were indicated for the four factors of attentional deficit/hyperactivity, oppositional behavior, conduct disorder symptoms and avoidance behaviors. The externalizing childhood problems (i.e., attentional deficit/hyperactivity, oppositional behavior, conduct disorder) were associated significantly with both internalizing (depression) and externalizing (e.g., alcohol consumption, delinquent activity) adolescent problem behaviors, as well as with an earlier age of onset for substance use. Avoidant behaviors in childhood were associated specifically with depressive symptomatology in adolescence. Results are discussed with regard to the role of childhood problems as precursors to adolescent/adult disorders. PMID- 8341045 TI - Alcohol consumption among emergency room patients: comparison of county/community hospitals and an HMO. AB - This study examines the associations of drinking patterns and problems to injury vs noninjury status among emergency room (ER) patients. Data come from two distinctly different health care systems in the same county: (1) the county hospital and three community hospitals (N = 2,626) and (2) the three health maintenance organization (HMO) hospitals (N = 1,102). Results indicate that alcohol's role in injury cases seen in the ER differs from its contribution to noninjury cases. Further, the demographic characteristics of ER populations--and the associated drinking patterns--also vary from site to site, and these also affect the contribution of alcohol to events requiring ER treatment. Both studies used similar methods and data collection instruments. Probability samples of patients were breath analyzed and interviewed regarding self-reported consumption (within 6 hours prior to the injury or illness), usual drinking patterns and alcohol-related problems. In both samples injured were more likely than noninjured to have positive breath-analyzer readings and to report heavy drinking, more frequent drunkenness, prior alcohol-related accidents and prior treatment for an alcohol-related problem, but were no more likely to report harmful consequences of drinking or alcohol dependence experiences during the last year. Both injured and noninjured in the county/community sample reported higher rates of heavy and problem drinking than their counterparts in the HMO sample, while those in the HMO sample reported rates for heavy and problem drinking similar to those found in the general population of the county.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341046 TI - Alcohol's effect on fatality risk from a physical insult. AB - Although alcohol's effect on the risk of being involved in a traffic crash is well known, its influence on the risk of death, given that a crash has occurred, is more uncertain. One study published a few years ago finds that alcohol increases such risk. The present study examines alcohol's effect on fatality risk in a crash using data and methods independent of the previous study, and provides estimates as a function of blood alcohol concentration (BAC). Data for drivers with measured BAC who were fatally injured in a two-car crash were selected from the Fatal Accident Reporting System (FARS). The study uses two sets of fatal crashes. For one, the probability that a BAC = 0 driver was killed is low, so that if alcohol increased fatality risk, this would generate additional fatalities at higher BAC levels. For the other set of crashes, fatality risk was sufficiently close to 100% that other factors had little opportunity to influence it. Dividing the fatalities that can be affected by alcohol by those that cannot measures alcohol's influence on fatality risk, and gives that a driver with BAC = 0.1% is 1.9 +/- 0.2 times as likely as is a BAC = 0 driver to be killed in the same crash. The corresponding ratio for a BAC = 0.25% driver is 3.3 +/- 0.5. While derived using the "laboratory" of traffic, there does not appear to be any obvious reason why the results should not apply to physical trauma in general, so a BAC of 0.1% doubles the risk of death from a given impact, and a BAC of 0.25% triples the risk. PMID- 8341047 TI - Average daily alcohol consumption during adult life among decedents with and without cirrhosis: the 1986 National Mortality Followback Survey. AB - The relationship of alcohol consumption and cirrhosis mortality was examined by sampling 1% of deaths in the U.S. using the 1986 National Mortality Followback Survey. Quantity and frequency of decedent's alcohol consumption was obtained from next of kin through mailed questionnaire. The percentage of decedents with cirrhosis increased sharply with the increasing number of drinks per day. Three drinks per day was associated with a significantly higher percentage of cirrhosis deaths compared with lifetime abstainers for both whites and blacks. Although blacks had a significantly higher percentage of abstainers than whites, of those persons who were reported to drink every day, blacks were more likely to be heavier drinkers (5 or more drinks per day). Blacks did not have a higher risk of cirrhosis mortality than whites for each drinking category. Although Native Americans were oversampled, the number of deaths was too small for statistical comparisons. PMID- 8341048 TI - Important characteristics of warning displays on alcohol containers. AB - Four studies examined the federally mandated warning on alcohol containers, which is required by law to be "located in a conspicuous and prominent place." In all four studies few of the drinkers could recall the main parts of the warnings, even though the warning had been required on all alcohol containers for over two years. In Study 1, 44 adults looked at the warning on various beer containers and 77% thought that the warning was not conspicuous but could be made conspicuous through various changes, such as by printing the warning horizontally (parallel to the brand name) rather than vertically. In Study 2, 50 adults looked at the warning placed horizontally on one beer can and vertically on a similar can and rated the horizontal warning significantly more conspicuous. In Study 3, 44 adults spent several minutes in a simulated drinking atmosphere. Half the subjects had beer cans with a horizontal warning and half had a vertical warning. The subjects with the horizontal warning later showed significantly better awareness/recall of the warning. In Study 4, with 75 adult subjects in a bar, the half of the subjects prompted to notice the alcohol warning drank less thereafter in the bar than the other subjects. The findings of the series of studies suggest that the conspicuousness of health warnings on alcohol containers tends to influence their possible effectiveness. PMID- 8341049 TI - Privatization, price and cross-border liquor purchases. AB - Self-report survey data were used to investigate the effects of liquor sales privatization on cross-border liquor purchases. A state survey sample representing the Iowa age 18+ noninstitutionalized population was interviewed in April 1989, some 25 months after retail spirits sales were privatized. Despite a privatization induced 6.1% increase in retail liquor prices, there was little, if any, change in the self-reported amount of liquor purchased outside the state of Iowa. PMID- 8341050 TI - The effect of social investment on treatment outcome. AB - Social support is associated with better response to treatment. Treatments focused on relationships, such as marital and family therapy, are directed in part at promoting this support. However, the strength of the relationship between support and abstinence is modest, as is the demonstrated incremental effectiveness of treatments focused on relationships. Treatment-matching research needs to determine under what set of conditions treatments focused on relationships will enhance abstinence. The primary aim of this study was to determine whether the relationship between alcohol involvement and alcohol specific social support is moderated by a person's social investment. The second aim was to determine the set of circumstances under which extended individually focused cognitive behavioral (CB) treatment and a relationship enhancement (RE) of brief cognitive behavioral treatments would improve outcomes. Patients were randomly assigned to individual or relationship-enhanced outpatient treatment and followed for 12 months. Results indicated that a patient's social investment did moderate the strength of the relationship between support and posttreatment alcohol involvement: Among high investors, there was a strong positive relationship, while the association was weak for low investors. A hypothesized triple-order interaction between social investment, posttreatment support and treatment did not materialize. However, an interaction between support and treatment showed that those with high support did equally well in either treatment, while those posttreatment support was low benefited from CB, but experienced poor outcomes when treated in relationship enhancement of CB. Further analyses indicated that increasing alcohol-specific support for low investors was probably contraindicated. We suggest that patients with low investment should be treated in an extended cognitive behavioral modality, while relationally enhanced CB treatment should be limited to high investors who are likely to experience support for their abstinence following treatment. PMID- 8341051 TI - Differences among AA groups: implications for research. AB - Clinical writings and research often imply the homogeneity of Alcoholics Anonymous. Survey data from four groups reflected some consistencies as well as substantial variation in group environment that could have an important impact on outcomes and research. PMID- 8341052 TI - Why not breast conservation? PMID- 8341053 TI - Immunohistochemical study of estrogen receptor and estradiol on papillary thyroid carcinoma in young patients. AB - We have immunohistochemically examined estrogen receptors (ER) and estradiol (E2) on papillary thyroid carcinoma in young females under the age of 25 years. The 10 young females in this study were compared with 64 females 30 years of age or older who underwent surgery for treatment of papillary thyroid carcinoma. We did not find any significant difference in the incidences of positive staining for E2 between the two groups. Of the specimens obtained from the young patients, 80% (8/10) showed positive staining for ER; this was significantly higher (P < 0.01) than that observed in patients 30 years of age or older (25%). We think that, especially in youth, estrogen may play an important role as a promoting factor. This indication needs further study. PMID- 8341054 TI - Carcinoembryonic antigen (CEA) in stage IV gastric cancer as a risk factor for liver metastasis: a univariate and multivariate analysis. AB - Serum carcinoembryonic antigen (CEA) levels were determined in 68 patients with Stage IV gastric cancers, the objective being to examine the clinicopathological relationship between the metastatic patterns of gastric cancer and the serum CEA level. Of the 68 patients, 31 were diagnosed as cases of liver metastases and 37 as cases of peritoneal dissemination. Serum CEA levels were elevated in 21 of 31 patients (67.8%) with liver metastases and in 7 of 37 patients (18.9%) with peritoneal dissemination (P < 0.01). A univariate analysis showed that liver metastasis correlated with a young age (P < 0.01), the lower portion of stomach (P < 0.05), Borrmann types 1 and 2 (P < 0.01), differentiated type (P < 0.01), and nonserosal involvement (P < 0.05) more than did peritoneal dissemination. A multivariate analysis showed that in addition to Borrmann type 1 and 2, elevated CEA levels (> 2.5 ng/ml) is an independent risk factor involved in liver metastasis. Thus careful follow-up and postoperative adjuvant therapy are required for patients with elevated CEA levels, even with "curative" resection. PMID- 8341055 TI - Pulmonary metastases from adrenal cortical carcinoma: results of resection. AB - Adrenal cortical carcinoma is uncommon. There is little controversy concerning treatment of the primary tumor. However, data concerning the treatment of pulmonary metastases are sparse. In order to assess the results of therapy, we reviewed our 14-year experience. Records of 24 patients admitted to our institution from 1973 to 1991 with the diagnosis of adrenal cortical carcinoma and pulmonary metastases were reviewed. Ten patients underwent pulmonary resection, 12 received chemotherapy, and 2 no therapy. In the pulmonary resection group, treatment consisted of wedge resection in 8 patients and lobectomy in 2. For the 10 patients undergoing resection of their pulmonary metastases, the 5 year survival was 71% (median not reached at 5 years). This was significantly longer than those not resected, with no one alive at 3 years (median survival 11 months). Our data suggest that those patients who are able to have their pulmonary metastases resected survive significantly longer than those who do not. PMID- 8341056 TI - Prognostic value of the number of metastatic lymph nodes in gastric cancer with radical surgery. AB - To evaluate the effectiveness of extended lymph node dissection in gastric cancer, the relationship between the number of lymph nodes with metastasis and the long-term outcome was studied retrospectively in 761 patients who underwent curative resection with extensive lymph node dissection. The cumulative 5-year survival rate was 85.8% in patients without lymph node metastasis, 60.2% in those with 1-4 lymph nodes, 35.6% with 5-10 nodes, and 12.3% with 11 or more nodes involved. Concerning N2 or N3 patients in whom metastatic lymph nodes would have remained without extensive dissection, the 5-year survival rate was 70.5% in those with 1-4 lymph nodes involved and 44.0% with 5 or more lymph nodes involved when no serosal invasion was observed. It was 38.5% with 1-4 lymph nodes and 5% with 5 or more lymph nodes involved when serosal invasion was observed. These results suggest that extensive lymph node dissection is effective in gastric cancer patients without serosal invasion and, when only a few lymph nodes are involved, also in those with serosal invasion. However, it is not considered to be effective in patients with serosal invasion and metastasis to many lymph nodes. Combination therapies are thought to be required in such patients. PMID- 8341057 TI - Flow cytometric DNA analysis of interleukin-2 responsive renal cell carcinoma. AB - Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p2 = 0.10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population. PMID- 8341058 TI - Changes in histopathological features of gastric carcinoma over a 26-year period (1965-1990). AB - Epidemiological study has shown that the incidence rate of gastric carcinoma in Japan has declined recently. To explore the factors that have influenced this decrease, the changing pattern in clinico-pathological features of gastric carcinoma was studied from the epidemiological point of view. The 5,015 cases of gastric carcinoma treated with gastrectomy at Aichi Cancer Center Hospital from 1965-1990 were divided into two histopathological types: the well-differentiated and other types. Proportional distribution was compared over the three different periods (1965-1973, 1974-1982, 1983-1990) according to the clinico-pathological features of the gastric carcinoma, i.e., sex, age, lesional location, etc. The recent relative decline of gastric carcinoma is due mainly to the decline of carcinoma of the well-differentiated type. This decline has been highly correlated to the decline in carcinoma of the antrum, which has been the most common in Japan. This changing pattern of clinicopathological features of Japanese gastric carcinoma might be affected by the change of exposure patterns to epidemiological factors, i.e., a Westernizing diet. PMID- 8341059 TI - Total pelvic exenteration with preservation of fecal continence. AB - Total pelvic exenteration may be required in the management of locally advanced or recurrent pelvic malignancy. Although prolonged survival may be achieved, the morbidity of this procedure is substantial. Many of the complications associated with total pelvic exenteration are related to the perineal wound, the necessity for two cutaneous stomas, and the creation of a empty pelvis that often has been previously irradiated. In selected cases, perineal preservation with restoration of coloanal continuity may significantly reduce postoperative morbidity. We report four cases of recurrent pelvic malignancy treated by total pelvic exenteration with preservation of fecal continence. PMID- 8341060 TI - In memoriam Hiram Thomas Langston (1912-1992). PMID- 8341061 TI - Comparison of open versus thoracoscopic lung biopsy for diffuse infiltrative pulmonary disease. AB - BACKGROUND: Patients with diffuse pulmonary infiltrates often require biopsy for a diagnosis. Standard operative therapy, open wedge resection via thoracotomy, is associated with known morbidity. We hypothesized that closed thoracoscopic wedge resection may result in reduced morbidity and decreased duration of hospital stay. This retrospective study compares open resection with thoracoscopic wedge resection in patients with diffuse pulmonary infiltrates. METHODS: Seventy-five patients with diffuse pulmonary infiltrates underwent diagnostic lung biopsy. Patients requiring mechanical ventilation and high levels of pressure support before biopsy were excluded from the study. Between March 1987 and September 1991, a total of 28 patients underwent open wedge resection via lateral thoracotomy. Since April 1991, a total of 47 patients underwent thoracoscopic resection. RESULTS: There was no difference between the groups in age, sex, presence of immunosuppression, or final pathologic diagnosis. Adequate tissue was obtained for pathologic diagnosis in all patients of both groups. All surgeons believed that thoracoscopic biopsy provided better visualization of the entire lung than did a limited thoracotomy. Mean operative time was 69 minutes for open biopsies and 93 minutes for thoracoscopic biopsies [p = 0.038]. Mean duration of chest tube drainage was not significantly different between the two groups. Duration of hospital stay was significantly less for thoracoscopic biopsy (4.9 days) than for open biopsy (12.2 days) (p = 0.018). Fourteen of 28 open biopsies resulted in complications compared with 9 of 47 closed biopsies (p = 0.009). There were 6 deaths among patients having open biopsies and 3 deaths among those having closed biopsies (p = not significant). CONCLUSION: A significant decrease in hospital stay was noted with thoracoscopic biopsy when compared with lung biopsy via the standard open approaches. Thoracoscopy provided excellent visualization and allowed for wedge resection that provided adequate tissue for diagnosis in patients with diffuse pulmonary interstitial disease. PMID- 8341062 TI - Transhiatal versus transthoracic esophagectomy for esophageal cancer. AB - We retrospectively analyzed 238 patients with esophageal carcinoma treated between 1983 and 1991; 120 underwent transthoracic esophagectomy, and 118 underwent transhiatal esophagectomy. The two groups were statistically similar in preoperative characteristics, except that upper esophageal cancer was more frequent in the transhiatal esophagectomy group than in the transthoracic esophagectomy group (p < 0.01). The rate of postoperative complications differed significantly in wound infection (21% in patients who underwent transthoracic esophagectomy, 10% in those who underwent transhiatal esophagectomy; p < 0.05) and empyema (11% with transthoracic esophagectomy, 1% with transhiatal esophagectomy; p < 0.01). Pneumothorax was detected in 24% of the transhiatal esophagectomy cases. Intraoperative blood loss was 1340 +/- 490 ml in the transthoracic esophagectomy group and 930 +/- 340 ml in the transhiatal esophagectomy group (p < 0.001). Hospital mortality was 11% in the transthoracic esophagectomy group and 6.7% in the transhiatal esophagectomy group. Late complication rate was lower with transhiatal esophagectomy than with transthoracic esophagectomy (11% and 51%, respectively). There was no significant difference in actuarial survival of patients in both groups. Transhiatal esophagectomy, which can be performed in almost all levels of the esophagus, is the safer of the two operations. PMID- 8341063 TI - Conduit reconstruction of the right ventricular outflow tract. Lessons learned in a twelve-year experience. AB - From September 1979 to July 1991, a total of 163 patients have undergone valved conduit reconstruction of the right ventricular outflow tract when a right ventricle-pulmonary artery connection was absent or right ventricular outflow tract enlargement was required. From September 1979 through October 1984, 24 porcine valved conduits were implanted with an operative mortality of 38% (9/24). There were no early failures, but by 9 years after the operation 9 of 15 survivors (60%) had severe conduit obstruction, which resulted in death in 2 patients and reoperation in 6. From May 1985 to June 1991, 24 patients received cryopreserved aortic allografts to correct congenital anomalies. Operative mortality was 25% (6/24) and, again, early conduit function was good. There were 4 (22%) late deaths that were not related to the aortic allograft. At a mean follow-up of 3.4 years, 11 of the 13 survivors (85%) had allograft calcification and 8 of the 13 (62%) had mild to moderate conduit stenosis or regurgitation, or both; two of them required conduit replacement. Distal anastomotic problems that might have been avoided with bifurcated pulmonary allografts were apparent in 4 (36%) patients. Cryopreserved pulmonary allografts were placed in 115 patients between April 1985 and January 1991, with 18 (16%) operative deaths. Late deaths that were not allograft related occurred in 7 of 97 surviving patients (7%). Six patients (6%) underwent reoperation, 2 because of primary pulmonary allograft failure. The 84 remaining patients are free of symptoms with little or no allograft calcification or echocardiographic evidence of significant conduit stenosis or regurgitation. Experience with porcine valved conduits and aortic and pulmonary allografts suggests that pulmonary allografts are the conduit of choice for right ventricular outflow tract reconstruction. PMID- 8341064 TI - Primary unifocalization for the absence of intrapericardial pulmonary arteries in the neonate. AB - The management of the neonate with absence of intrapericardial pulmonary arteries in association with complex intracardiac anomalies presents a challenging surgical problem. The more traditional approach of palliation with unilateral or bilateral systemic-pulmonary artery shunts may result in peripheral pulmonary artery stenoses and uneven distribution of pulmonary blood flow. In addition, this approach may lead to complicated reconstructive procedures necessitating reconstruction of the branch pulmonary artery with prosthetic material, which restricts pulmonary artery growth and often complicates reoperation. To avoid these potential limitations, we have performed primary unifocalization for absence of intrapericardial pulmonary arteries in eight consecutive neonates (median age 9 days) between May 1990 and December 1991. Absence of intrapericardial pulmonary arteries occurred in association with tetralogy of Fallot (n = 4), truncus arteriosus (n = 2), and transposition of the great arteries with pulmonary atresia (n = 2). Four patients had unilateral absence of the right (n = 1) or left (n = 3) intrapericardial pulmonary artery. In the remaining four patients, there was complete absence of both intrapericardial pulmonary arteries. Wide mobilization and excision of all ductal tissue before anastomosis was performed from a midline approach in seven patients. In one patient, a preliminary right thoracotomy was required. Primary unifocalization was performed simultaneously with complete repair in five patients. In the remaining three patients, unifocalization was part of a staged repair and included insertion of a systemic-pulmonary artery shunt to the reconstructed central pulmonary artery confluence. No operative or late cardiac deaths occurred, although one death occurred during subsequent repair of a tracheoesophageal fistula. Three patients underwent reoperation, and only one patient required revision of an anastomotic pulmonary artery stenosis. All survivors were growing normally at 2 to 22 months after operation (mean follow-up 10 months). Our experience suggests that primary reconstruction for the absence of intrapericardial pulmonary arteries can be successfully accomplished in the neonate. This approach provides uniform bilateral pulmonary blood flow, avoids prosthetic material in the branch pulmonary arteries, and may eliminate, or at least simplify, future reconstructive procedures. PMID- 8341065 TI - Biventricular repair of cardiac isomerism with common atrioventricular canal with the aid of an endocardial cushion prosthesis. AB - Between 1983 and 1990, six patients with atrial isomerism associated with common atrioventricular canal and double-outlet right ventricle were operated on with the aid of an endocardial cushion prosthesis. This prosthesis, which has been used for the repair of common atrioventricular canal since 1975, is composed of a vertical Dacron patch and "wings" constructed from the patient's own pericardium, which are attached to both sides of the patch to compensate for the defective atrioventricular valve tissue. The ventricular portion of the patch was extended anteriorly to construct the route for blood flow from the left ventricle to the aorta. Intraventricular repair was performed through the common atrioventricular orifice in all patients and also through an additional right ventriculotomy in one patient. The complex systemic and pulmonary venous return was separated by use of the atrial part of the endocardial cushion prosthesis together with additional prosthetic materials. All patients survived the operation and were followed up from 1 to 9 years. All of them are doing well, although one patient has a significant interventricular residual shunt. Repair of atrial isomerism with common atrioventricular canal and double-outlet right ventricle with an endocardial cushion prosthesis was performed with satisfactory immediate and intermediate-term postoperative results. PMID- 8341066 TI - Pulmonary atresia, intact ventricular septum, and Ebstein anomaly of the tricuspid valve. Anatomic and surgical considerations. AB - Pulmonary atresia with intact ventricular septum is a disorder that involves the whole right ventricle. An associated Ebstein deformity of the tricuspid valve is found in 10% of the cases, further complicating the anatomy and the function of the right ventricle. From January 1966 to December 1990, pulmonary atresia, intact ventricular septum, and Ebstein deformity of the tricuspid valve were observed in 11 cases in our institution; four of them were necropsy findings and the remaining seven were patients treated surgically. Of the latter, two were boys and five were girls (age range 1 day to 18 days). Two patients were managed by pulmonary valvotomy, three by systemic-pulmonary artery shunt, and two had a combination of the two. Operative mortality was 57%. Eight hearts were available for morphologic study. All had viscero-atrial situs solitus, D-loop ventricular structure, and normally related great arteries. A correlation between the degree of tricuspid valve dysplasia and right ventricular cavity size was observed in all. Furthermore, in five cases the anterior leaflet of the tricuspid valve obstructed the right ventricle at the ostium infundibuli level. In two of our surgical patients, a protruding anterior tricuspid valve leaflet was identified and excised and both patients survived. Ebstein anomaly of the tricuspid valve further complicates surgical management and outcome of pulmonary atresia and intact ventricular septum. Potential obstruction at the ostium infundibuli level should always be considered during repair. Various degrees of right ventricular inlet dysplasia, always present in this complex, may contraindicate an anatomic correction. In these cases a modified Fontan-type procedure should be considered as a valid surgical option. PMID- 8341067 TI - Lipid peroxidation and changes in vitamin E levels during coronary artery bypass grafting. AB - The effects of ischemia and reperfusion on arterial and coronary sinus vitamin E and thiobarbituric acid reactive substance levels were investigated in 10 patients undergoing routine coronary artery bypass grafting. Serial sampling was performed during bypass operations, before the initial period of crossclamping and at 30 seconds and 2, 5, and 10 minutes after final crossclamp removal. A net myocardial loss of vitamin E occurred in the first 5 minutes of myocardial reperfusion (0.84 +/- 0.21 mumol/mmol cholesterol; p < 0.01). Myocardial vitamin E loss correlated positively with the total crossclamp time (rho = -0.695; p < 0.05) but was independent of cardiac enzyme release and duration of cardiopulmonary bypass. The concentration of thiobarbituric acid reactive substance rose significantly in the systemic circulation (+14 nmol/gm albumin; F > 17; p < 0.002) at 2 and 5 minutes after crossclamp removal. A significant increase of thiobarbituric acid reactive substance levels was also found in the coronary sinus blood 10 minutes after crossclamp removal (+8 nmol/gm albumin; F > 14; p < 0.004). However, there was no net arterial-coronary sinus difference in thiobarbituric acid reactive substance levels. The change in arterial thiobarbituric acid reactive substance levels in each patient was inversely correlated with their control vitamin E level (F = 9.53; p < 0.01). Our findings suggest that systemic lipid peroxidation occurs during bypass and that vitamin E may play a protective role during routine bypass grafting by attenuating the degree of peroxidative damage. PMID- 8341068 TI - Transcaval liver resection with hepatoatrial anastomosis for treatment of patients with the Budd-Chiari syndrome. Late results. AB - Between 1980 and 1990 transcaval liver resection with hepatoatrial anastomosis was performed in 17 patients with the Budd-Chiari syndrome. There were two early deaths (early mortality 11.7%). Hepatic function returned to normal and hepatosplenomegaly disappeared in all but two patients with preexisting cirrhosis. All survivors regained normal working capacity after the operation. During an average follow-up of 6 years (7 months to 11 years) there were three late deaths due to progression of the underlying disease. The actuarial 1-, 5-, and 10-year survivals were 82%, 76%, and 57%, respectively. Hepatoatrial anastomosis represents an optimal treatment for patients with the Budd-Chiari syndrome and obstruction of major hepatic veins. Patients with compression of the inferior vena cava, very common in this disease, were treated by simultaneous transcaval stenting. The late results are very satisfactory, with excellent quality of life. With adequate hepatic function, results of hepatoatrial anastomosis are superior to those of liver transplantation, which represents the only alternative for patients with the advanced form of the Budd-Chiari syndrome. PMID- 8341069 TI - Experience with four surgical techniques to repair traumatic aortic pseudoaneurysm. AB - We report our experience with 27 (22 male and 5 female) patients who were from 16 to 82 years of age (median 29 years) who underwent surgical repair for traumatic pseudoaneurysm of the thoracic aorta. The cause of injury in all cases was blunt trauma. Repair was accomplished with partial bypass by means of a roller pump with systemic heparinization in 6 (23%), Gott shunt in 7 (27%), clamp-and-sew technique in 6 (23%), and centrifugal pump without systemic heparinization in 8 (30%). Significant postoperative complications occurred in 12 patients. Paraplegia occurred in 1 patient (clamp and sew), anterior spinal cord syndrome in 1 (clamp and sew), renal failure in 1 (Gott shunt), temporary vocal cord paralysis in 2 (Gott shunt, centrifugal pump), permanent vocal cord paralysis in 1 (roller pump), and coagulopathy in 2 (centrifugal pump, Gott shunt). Hospital mortality occurred in 5 of 27 (19%), (1 clamp and sew, 1 Gott shunt, 1 centrifugal pump, 2 roller pump). Follow-up of survivors (1 week to 20 years, median 2.1 years) revealed no further problems from either aortic graft or primary repair. Although patient numbers are small, evaluation of each of the four surgical techniques leads us to favor repair with shunting with a centrifugal pump without heparin. The potential advantage of left atrial-left femoral artery shunt with centrifugal pump support was evident in operative field exposure, afterload reduction, avoidance of clamp injury, and maintenance of stable distal aortic perfusion without heparin. PMID- 8341070 TI - Is zero-pressure fixation of bioprosthetic valves truly stress free? AB - Zero-pressure fixation has often been referred to as stress-free fixation, which implies that no leaflet stresses exist during the fixation process. The two aortic valve cusp layers, the fibrosa and the ventricularis, however, are believed to produce mutually opposing forces within the valve cusps. Residual stresses may therefore exist even during zero-pressure fixation. We first verified the presence of such internal stresses by separating the layers of pig aortic valve leaflets and measuring dimensional changes. In the 11 specimens examined, the fibrosa expanded radially by 30% +/- 13% (mean +/- standard deviation), whereas the ventricularis contracted by 12% +/- 4%. The ventricularis also contracted circumferentially by 13% +/- 3%. We measured the extensibility of 120 fresh and glutaraldehyde-fixed fibrosa and ventricularis components to investigate the mechanical effects of glutaraldehyde fixation under such internal stresses. We also tested the layers from leaflets that were fixed whole. We compared the extensibility of the fibrosa and the ventricularis, each fixed in the presence and absence of residual stresses, and found that, in the radial directions, the ventricularis from valve cusps that were fixed whole was less extensible than fresh ventricularis (35.4% versus 63.7% strain to high-modulus phase, p < 0.00001). The fibrosa from cusps that were fixed whole, however, was more extensible than fresh fibrosa (39.2% versus 29.5% strain, p < 0.0122 radially; 12.8% versus 8.2% strain, p < 0.0001 circumferentially). The ventricularis became less extensible because it was fixed under tension, and the fibrosa became more extensible because it was fixed under compression. This study therefore demonstrates the presence of residual tensile and compressive stresses in the ventricularis and fibrosa, even when the leaflets are relaxed. Zero pressure fixation cannot therefore be considered truly stress free, in the engineering sense, because residual internal stresses affect collagen fiber crimp and change the extensibility of the fibrosa and the ventricularis. PMID- 8341071 TI - Comparative outcome of heart-lung and lung transplantation for pulmonary hypertension. AB - Despite the development of several lung transplantation procedures, the most advantageous for pulmonary hypertension remains controversial. Between 1986 and February 1992, 30 patients with end-stage primary pulmonary hypertension (n = 24), chronic pulmonary embolism (n = 4), and hystiocytosis X (n = 2) underwent heart-lung (n = 21), double lung (n = 8), or single lung (n = 1) transplantation. Indications for double lung transplantation were similar to those for heart-lung transplantation, and the preoperative clinical and hemodynamic parameters were not significantly different between the two groups. There were no intraoperative deaths, but two reoperations were needed for pleural hematoma. Five early deaths were related to graft failure (two heart-lung transplantations), mediastinitis (one heart-lung transplantation), multiorgan failure (one double lung transplantation), and aspergillosis (one double lung transplantation). There was a similar improvement in early (days 0 and 2) and late (6 months postoperatively) right-sided hemodynamic function in patients undergoing heart-lung and double lung transplantation. Three double lung transplant recipients had early and reversible left ventricular-failure. The early postoperative course of the one patient who had single lung transplantation was characterized by severe pulmonary edema, left ventricular failure, and persistent desaturation and later on by moderate pulmonary hypertension and an important ventilation/perfusion mismatch. The pulmonary function results were also similar in the heart-lung and double lung transplantation groups. The overall projected 2- and 4-year survivals were 49% and 41%, respectively, and were not significantly different between the heart lung and double lung recipients. Results demonstrate that heart-lung and double lung transplantation are equally effective in obtaining early and durable right sided hemodynamic and respiratory improvement and similar respiratory function. In patients with pulmonary hypertension, double lung transplantation should be preferred to single lung transplantation because of the critical postoperative course and the uncertain long-term results of single lung transplantation. PMID- 8341072 TI - A technique for perfusion of an isolated working heart to investigate hyperacute discordant xenograft rejection. AB - We developed an isolated working heart preparation to investigate hyperacute rejection of discordant xenografts. It is possible to correlate organ failure with the rejection process, and end points of rejection are easily identified. This unique model permits easy sampling of perfusates and examination of the rejected organ. The perfusate may be modified in ways not possible in in vivo preparations. Investigation of the discordant rabbit-to-pig combination with the technique has confirmed that hyperacute xenograft rejection can be reproduced. Rejection appears to be a complement-mediated immunologic phenomenon rather than the consequence of a nonspecific physical incompatibility. Hyperacute xenograft rejection can be prevented by depletion of C3 from the perfusing blood by treatment with cobra venom factor. PMID- 8341073 TI - Venovenous compares favorably with venoarterial access for extracorporeal membrane oxygenation in neonatal respiratory failure. AB - Traditional extracorporeal membrane oxygenation via the venoarterial route requires cannulation and ligation of the internal jugular vein and common carotid artery. Concerns about ligation of the common carotid artery prompted development of a 14F double-lumen internal jugular vein cannula for venovenous oxygenation for neonates with respiratory failure. We retrospectively compared 22 patients supported by venovenous bypass and 20 patients supported with traditional venoarterial bypass. The two groups of patients were selected to be comparable in terms of diagnosis and severity of respiratory insufficiency. The diagnoses in both groups were limited to meconium aspiration syndrome or persistent pulmonary hypertension of the newborn. The average oxygenation indexes in the two groups were similar (46.6 venovenous, 47.2 venoarterial, p = not significant). Venovenous access allowed flow rates of more than 100 ml/kg per minute, which were adequate for gas exchange support. One patient required conversion from venovenous to venoarterial bypass because of hemodynamic instability. The average time of bypass support was 115 hours (range 24 to 338 hours) for venovenous bypass and 134 hours (range 47 to 361 hours) for venoarterial bypass (p < 0.05). The time to extubation after decannulation from extracorporeal membrane oxygenation was 133 hours (range 38 to 720 hours) for venovenous support and 100 hours (range 27 to 192 hours) for venoarterial support (p = not significant). One patient supported with venoarterial bypass had an intracranial hemorrhage. There were no documented neurologic injuries in the patients managed with venovenous bypass. There were no deaths in either group. Venovenous extracorporeal membrane oxygenation through a double-lumen cannula can adequately provide respiratory support for neonates with pulmonary failure and effectively avoids ligation of the common carotid artery. PMID- 8341074 TI - Changes in pericardial morphology and fibrinolytic activity during cardiopulmonary bypass. AB - The presence of pericardial adhesions at resternotomy not only increases the operation time but also increases the risk of serious damage to the heart, great vessels, and extracardiac grafts. The reported prevalence of damage is 2% to 6%. The fibrinolytic activity of pericardial tissue may be a crucial factor in determining the extent of adhesion formation following primary operation. Ten patients undergoing cardiac operations were studied to assess the plasminogen activating activity of homogenates of pericardial tissue samples. Samples were taken at three times during the operation and the plasminogen activating activity was measured by means of a standard fibrin plate technique. Tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and plasminogen activator inhibitor-2 were also measured by means of enzyme-linked immunosorbent assays. Compared with its initial levels (median 2.06 IU/cm2, range 1.28 to 6.48 IU/cm2), the plasminogen activating activity of pericardial biopsy tissue was significantly reduced at 75 minutes (median 0.64 IU/cm2, range 0.12 to 2.44 IU/cm2, p < 0.01) and at 135 minutes (median 1.45 IU/cm2, range 0.12 to 4.39 IU/cm2, p < 0.05). The major plasminogen activator present was tissue-type plasminogen activator. Compared with its initial levels (median 2.34 ng/ml, range 1.03 to 6.42 ng/ml), subsequent tissue type plasminogen activator values were also significantly reduced at 75 minutes (median 0.83 ng/ml, range 0.75 to 5.13 ng/ml, p < 0.005) and at 135 minutes (median 1.24 ng/ml, range 0.75 to 6.67 ng/ml, p < 0.05). Low levels of urokinase type plasminogen activator were found in 5 of 10 patients. However, neither plasminogen activator inhibitor-1 nor plasminogen activator inhibitor-2 was detected. Examination with a light microscope showed both increasing pericardial mesothelial damage and increasing features of acute inflammatory changes with time. This study shows that plasminogen activating activity is present in pericardial tissue and that tissue-type plasminogen activator is the major plasminogen activator. The observed inflammatory changes and concomitant damage to the pericardial mesothelium, and the significant reductions in pericardial tissue-type plasminogen activator and plasminogen activating activity seen during cardiac operations, may be important factors contributing to the early development of pericardial adhesions. PMID- 8341075 TI - Effects of crossclamping the descending aorta on the high-energy phosphates of myocardium and skeletal muscle. A phosphorus 31-nuclear magnetic resonance study. AB - The study was designed to test the hypothesis that a moderate decrease in upper body oxygen consumption observed during crossclamping of the thoracic aorta represents tissue hypoxia (possibly as a result of microcirculatory disorders) and results in adenosine triphosphate homeostasis disturbances. We averaged phosphorus 31-nuclear magnetic resonance spectroscopy measurements for 10 minutes with the use of a surface coil on the left ventricle and on the deltoid muscle during a 1-hour period before aortic crossclamping, during aortic crossclamping, and after aortic unclamping. Skeletal muscle creatine phosphate levels decreased 3.1% (p < 0.01), whereas the ratio of creatine phosphate to adenosine triphosphate decreased 2.2% (p < 0.05); glycolytic intermediates increased 70% (p < 0.01) and intracellular inorganic phosphate decreased 9% (p < 0.01). Myocardial creatine phosphate decreased 15% (p < 0.01), whereas the ratio of creatine phosphate to adenosine triphosphate decreased 5.3% (p < 0.01); glycolytic intermediates did not change, but intracellular inorganic phosphate almost doubled (p < 0.05). These data suggest that observations of reduced upper body oxygen consumption after aortic crossclamping are consistent with the effects of skeletal muscle hypoxia. Changes in myocardial metabolites may result from transient ischemia caused by the increased wall stress. PMID- 8341076 TI - Detrimental effects of interrupting warm blood cardioplegia during coronary revascularization. AB - Warm blood cardioplegia has emerged as a substitute for cold blood cardioplegia as a method of myocardial protection. However, the continuous infusion of blood in this technique may obscure the operative field and necessitate interruption of warm blood cardioplegia. This experimental study was therefore undertaken to determine whether interrupting warm blood cardioplegia during coronary revascularization would increase myocardial damage. In 30 adult pigs, the second and third diagonal vessels were occluded with snares for 90 minutes. All animals underwent cardiopulmonary bypass and 45 minutes of cardioplegic arrest. During the period of cardioplegic arrest, 10 pigs received intermittent antegrade/retrograde infusion of cold blood cardioplegic solution (4 degrees C) 10 pigs received continuous retrograde infusion of warm blood cardioplegic solution (37 degrees C) at 100 ml/min, and 10 pigs received retrograde infusion of warm blood cardioplegic solution that was interrupted for three 7-minute periods. After aortic unclamping, the coronary snares were released and all hearts were reperfused for 180 minutes. Interrupting retrograde warm blood cardioplegia resulted in more tissue acidosis during cardioplegic arrest (6.20 +/ 0.16 interrupted retrograde warm blood cardioplegia and 6.45 +/- 0.12 continuous retrograde warm blood cardioplegia, both p < 0.05 compared with 6.98 +/- 0.17 intermittent antegrade and retrograde cold blood cardioplegia), decreased echocardiographic wall-motion scores (4 [normal] to -1 [dyskinesis]; 2.06 +/- 0.30 interrupted retrograde warm blood cardioplegia, p < 0.05 compared with 3.30 +/- 0.40 intermittent antegrade and retrograde cold blood cardioplegia, 2.80 +/- 0.40 continuous retrograde warm blood cardioplegia), and increased tissue necrosis as measured by the area of necrosis/area at risk (38% +/- 5% interrupted retrograde warm blood cardioplegia, p < 0.05 compared with 21% +/- 2% intermittent antegrade and retrograde cold blood cardioplegia; 25% +/- 2% continuous retrograde warm blood cardioplegia). We concluded that interrupting warm blood cardioplegia during coronary revascularization diminishes the effectiveness of warm blood cardioplegia and results in increased ischemic damage. PMID- 8341077 TI - Relation of pH strategy and developmental outcome after hypothermic circulatory arrest. AB - To examine whether pH management during core cooling is a risk factor for adverse developmental outcome, we studied 16 children with transposition of the great arteries and intact ventricular septum who underwent a Senning procedure in infancy (median age 32 days, range 2 to 154 days) between 1983 and 1988. Information was collected retrospectively on many aspects of perfusion, including lowest carbon dioxide tension during core cooling, duration of core cooling, and duration of circulatory arrest. The pH strategy changed from pH-stat to alpha stat in 1985, resulting in a wide range of pH values and carbon dioxide tension (34 to 76 mm Hg) during the study period. All children had rapid core cooling to a rectal temperature of 19.8 degrees +/- 2.7 degrees C (mean +/- standard deviation) and a tympanic temperature of 16.6 degrees +/- 3.0 degrees C. Development was assessed at median age 48.0 (11 to 79) months with the Bayley Scales (n = 4, children younger than 30 months) or the McCarthy Scales (n = 12, children older than 30 months). The mean core-cooling duration was 14.5 +/- 6.2 minutes, circulatory arrest time was 43.4 +/- 6.6 minutes, and total bypass plus circulatory arrest time was 89.7 +/- 12.7 minutes. Lower carbon dioxide tension (alpha-stat) before onset of circulatory arrest was associated with worse developmental outcome (r = 0.71, p = 0.002). This relationship remained highly significant when we controlled for sociodemographic and intraoperative variables. including core-cooling time, circulatory arrest time, and total elapsed time. Duration of circulatory arrest was not associated with developmental outcome. We conclude that when relatively rapid core cooling is used to achieve hypothermia before circulatory arrest in young infants, a more alkaline pH strategy such as alpha-stat may result in less effective cerebral protection. PMID- 8341078 TI - Inhaled nitric oxide in pulmonary hypertension after total repair of total anomalous pulmonary venous return. PMID- 8341079 TI - Retrograde cardioplegia and aortic valve replacement. PMID- 8341080 TI - Warm retrograde cardioplegia: protection of the right ventricle in mitral valve operations. PMID- 8341081 TI - Aortic valve rupture in closed trauma: the extent of the damage. PMID- 8341082 TI - Atresia of left atrioventricular valve and intact atrial septum with multiple congenital defects corrected by total cavopulmonary connection. PMID- 8341083 TI - Is two-dimensional echocardiography reliable in identifying cardiac injury? PMID- 8341084 TI - Controlled limb reperfusion as a new surgical technique to reduce postischemic syndrome. PMID- 8341085 TI - Simulated left ventricular aneurysm and aneurysm repair in swine. PMID- 8341086 TI - Inflammatory response of the lung to tungsten particles: an experimental study in mice submitted to intratracheal instillation of a calcium tungstate powder. AB - Tungsten has been implicated as a cause of a severe form of pneumoconiosis in humans, the so-called "hard metal" lung disease. We have investigated the effect of intratracheal instillation of a powder of calcium tungstate on the pulmonary tissue of CD-1 mice. The tungsten-induced alterations were studied using 3 microanatomical methods: cytologic study of exudates obtained by bronchoalveolar lavage (BAL); histologic examination of paraffin-embedded sections of the lung; and scanning electron microscopic (SEM) examination of lung samples using x-ray microanalysis to detect tungsten in situ. The animals were sacrificed 1, 3, 7, 14 and 21 days after a single intratracheal instillation of 250 micrograms calcium tungstate particles suspended in 100 microliters of saline. We found that the metal particles induced a marked inflammatory response in the bronchoalveolar space characterized by a biphasic attraction of leukocytes with cellular peaks observed at day 1 and 14. More than 50% of the BAL macrophages showed ingested tungsten. In the lung parenchyma, the inflammatory infiltrates were predominantly located at the periphery of the bronchiolar walls. From 7 days on after the tungsten deposition, large inflammatory exudates were seen invading focal areas of the alveolar domain of the lung. SEM views revealed that the tungsten particles could be inside alveolar macrophages, in cells making up the alveolar wall, or inside periacinar lymphatics. Our data document that tungsten particles cause a marked inflammatory response in the lung tissue and that the leukocyte exudates may invade alveolar areas of the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341087 TI - Aging, respiratory efforts during sleep, and pulsus paradoxus. AB - Forty patients with either obstructive sleep apnea syndrome or a clinical complaint of daytime sleepiness with measured nocturnal increase in upper airway resistance and snoring were investigated during sleep for the presence of pulsus paradoxus, which is defined as a decrease in systolic blood pressure (SBP) of at least 10 mmHg during inspiration. Two thirds of the subjects presented pulsus paradoxus. Age, lowest oxygen saturation (SaO2), and negative inspiratory esophageal pressure nadir (an index of inspiratory effort) were the only studied variables which could statistically dissociate patients presenting pulsus paradoxus. We then divided the patient population into three different subgroups of equal number based upon the degree of decrease in SBP (i.e., > 20 mmHg, < 20 but > 10 mmHg, and < 10 mmHg). In this second analysis, age was the only significant variable that separated the three groups. Lowest SaO2 could not be used to statistically separate subjects with mild to moderate pulsus paradoxus from those without it; and negative inspiratory esophageal pressure measurements could only significantly identify subjects with severe pulsus paradoxus (i.e., > 20 mmHg) from those without any pulsus paradoxus. The variable which correlated best with age was negative inspiratory esophageal pressure nadir (R = 0.83). Our interpretation is that as age increased, negative inspiratory esophageal pressure became less negative, due to the known impact of aging on muscles, and pulsus paradoxus was no longer observed. PMID- 8341088 TI - Airflow obstruction in nonsmoking, asbestos- and mixed dust-exposed workers. AB - Obstructive changes in small airways have been described in patients exposed to asbestos and other mineral dusts. The physiologic significance of these small airways abnormalities and their relationship to dust burden and alveolitis remain unclear. We performed bronchoalveolar lavage (BAL) in 30 nonsmoking and 30 age matched smoking subjects, all with mild asbestos and mixed dust exposure, to determine if parameters of lung dust burden correlated with spirometric evidence of airflow obstruction. Seventeen of 30 nonsmoking subjects and 24 of 30 smoking subjects met spirometric criteria for airflow obstruction. There were significantly more obstructed subjects in both dust exposed groups (P < 0.05) than in an age-matched nondust exposed group. There was, however, no significant difference in the number of obstructed subjects between the smoking and nonsmoking groups. There was no correlation in either group between airflow obstruction and total or differential cell counts, ferruginous bodies, total asbestos fibers, or the percent of free silica in the particulate fraction recovered by BAL. We conclude that evidence of small airways obstruction occurs commonly in occupationally dust exposed subjects and appears to be related to dust exposure per se and not to alveolar inflammation or fiber retention, important factors in the development of alveolitis and interstitial lung disease. PMID- 8341090 TI - A pulmonary rehabilitation program for patients with asthma and mild chronic obstructive pulmonary diseases (COPD). AB - The effects of a pulmonary rehabilitation program on 44 patients with chronic obstructive pulmonary disease (COPD) were compared to a control group. The treated group was admitted to the program for a period of three months. The program consisted of several parts, such as physical training, health education, and psychological and social matters. Before participation, the patients were thoroughly examined and provided with optimal medical treatment. Both groups were assessed by means of biometrical tests and questionnaires for a period of 2 years. The rehabilitation group improved significantly in endurance, psychological parameters, and consumption of medical care. Working days increased and their way of life became more active. Smoking habits and body fat percentage decreased. Bronchial hyperreactivity, need for pulmonary drugs, and coughing and sputum production did not improve in the rehabilitation group compared to the control group. Airway obstruction, expressed as forced expiratory volume in one second, and complaints of dyspnea, allergy and hyperreactivity scores on questionnaires improved only in the short term (< 1 year), but did not improve significantly in the long term. This study shows that pulmonary rehabilitation can result in improvements in patients with asthma or COPD who have many complaints despite the fact that their pulmonary function is not severely disturbed. PMID- 8341089 TI - Studies of phagocytic and killing activities of alveolar macrophages in patients with sarcoidosis. AB - Phagocytosis and killing activities of alveolar macrophages were compared in 17 patients with stage 1 sarcoidosis and 6 healthy controls. The average total cell count of bronchoalveolar lavage fluid from patients with sarcoidosis was 7.8 +/- 7.5 x 10(6) cells; 70.4 +/- 15% of these cells were alveolar macrophages and 25.9 +/- 16.2% lymphocytes. Average total cell count from controls was 8.33 +/- 8.6 x 10(6) cells, with 92.7 +/- 5.9% alveolar macrophages and 6.6 +/- 4.4% lymphocytes. Purified alveolar macrophages were tested in in vitro antibacterial assays using S. aureus as a test microbe. Moderate decreases in the kinetics of staphylococcal ingestion were detected in the sarcoidosis group. The intracellular killing activity of macrophages was much lower in the patients with sarcoid than in control subjects. In a pilot study, intracellular killing activity of macrophages from 1 patient with sarcoidosis was greatly enhanced by 24 hr treatment with transfer factor. In summary, alveolar macrophages from patients with radiographic stage 1 sarcoidosis have decreased bacterial ingestion and intracellular killing activities. These results suggest that macrophages undergo complex functional changes in sarcoidosis that may influence both disease development and host defenses. PMID- 8341091 TI - Breastfeeders versus bottlefeeders: differences in femininity perceptions. AB - Fifty-eight primiparous women were studied to explore perceived differences in femininity between women who chose to breastfeed and women who chose to bottlefeed. A demographic questionnaire and a sex role inventory were administered to the sample. Although breast and bottlefeeders did not differ significantly in their perceived levels of femininity, analysis of the data revealed that women who had no clear cut sense of identity were more likely to bottlefeed. PMID- 8341092 TI - Coping behaviors of children hospitalized for cardiac surgery: a secondary analysis. AB - While the coping behaviors of hospitalized children continue to be an area of interest for researchers, systematic documentation in the literature concerning children's coping remains limited. In this descriptive secondary analysis, 23 master's thesis case studies were analyzed to determine how researchers described the range of coping behaviors that children used while hospitalized for cardiac surgery. The analysis sought to determine patterns of coping in both preschool and school-age children. A second aim was to validate further and refine the dimensions and items of the Children's Coping Behaviors Category System developed by Ritchie, Caty, and Ellerton in 1987. Results revealed that a broad range of names and labels of behavior was used to describe children's coping. The predominant patterns of behavior that emerged were direct action and information seeking. Differences between preschool and school-age children's reported behaviors were evident. The coping category system was validated further and refinements are suggested. PMID- 8341093 TI - Pain in the infant: theoretical and conceptual issues. AB - Existing theories of pain are individually inadequate to explain pain in infants. There is limited understanding of how the physiological response to pain (nociception) relates to the cognitive and behavioral response of infants. Little knowledge exists on how the context in which pain is experienced affects physiological and behavioral responses. Lack of a clear conceptualization of pain in infants has implications for nursing practice and research, most notably in the area of pain assessment and management. Several theories must be considered to address the complexity and multidimensionality of pain in infants. PMID- 8341094 TI - Clinical comparisons of posturography and electronystagmography. AB - A retrospective study was conducted of 103 balance-disturbed patients of mixed etiologies tested with electronystagmography (ENG) and computerized dynamic posturography (CDP). CDP was abnormal for 83% of the group as compared to 42% abnormal ENG results. In cases of otolithic dysfunction, ENG was more sensitive and gave specific information. Results of this preliminary study indicate that CDP has merit when used in the evaluation of patients with undifferentiated balance complaints. ENG testing is still needed in cases of vestibular dysfunction to establish anatomic level and laterality as well as for lesions involving the otolith. Additional study will be needed to verify these findings and to develop a means of detecting otolith dysfunction with CDP. PMID- 8341095 TI - Evidence of IgE-mediated hypersensitivity in allergic fungal sinusitis. AB - Despite documentation of specific immunologic hypersensitivity in a few case reports, controversy continues as to the role of allergy versus true infection in the clinical entity of allergic fungal sinusitis (AFS). Using a modified radioallergosorbent test (RAST) to multiple fungal antigens, 16 patients meeting the histologic criteria of AFS and with positive fungal cultures were compared to 5 control patients with similar preoperative clinical findings but without histologic or culture evidence of AFS. All patients were immunocompetent and none demonstrated histologic evidence of tissue invasion. All AFS patients were RAST positive to at least one fungal antigen in the family of their cultured organism with positive defined as class 2 or greater. No control patient was RAST-positive to either dematiaceous or Aspergillus fungal antigens. Thus, modified RAST testing can aid in the routine clinical diagnosis of AFS, and it provides further serologic evidence for a type I hypersensitivity in the pathogenesis of AFS. PMID- 8341096 TI - Magnetic resonance imaging of perilymphatic fistula. AB - Perilymphatic fistula (PLF) is considered to be a most challenging otologic issue. There are no currently agreed upon objective tests for the diagnosis of PLF. In an effort to improve diagnostic accuracy in patients with suspected PLF, a novel diagnostic test involving magnetic resonance (MR) contrast imaging was designed. An experimental PLF was created in the cochlear round window membrane of healthy adult cats. Since cochlear perilymph is thought to be an ultrafiltrate of cerebral spinal fluid, gadodiamide (gadolinium-diethylenetriamine penta-acetic acid [DTPA] bismethylamide), a nonionic paramagnetic contrast agent, was injected intrathecally in an attempt to enhance imaging of the created fistula. Post contrast images of the fistualized cochlea demonstrate a significant increase in the signal intensity of the cochlear perilymph with pooling of enhanced perilymph observed in the ipsilateral mastoid bulla. Magnetic resonance contrast imaging may prove to be a valuable technique in human studies involving perilymphatic fistula. PMID- 8341097 TI - Electronic control of laryngeal spasm. II. Selective blockage of glottic adduction by a closed-loop circuit in the canine. AB - This work is the continuation of an earlier pilot study in which specially designed electrodes were used to block their own induced action potentials to restrain spasticity. In the current series of experiments, strap muscle and thyroarytenoid contraction (glottic closure) elicited by supramaximal ansa hypoglossi (N = 6) and recurrent laryngeal nerve (N = 4) stimulation (30 to 50 Hz, 0.1 to 6 mA, 0.1 to 1 msec), respectively, allowed afferent information via intramuscular sonomicrometer crystals to trigger a circuit that, in turn, stimulated blocking electrodes passed around the nerves downstream. Simultaneous videorecording of strap and vocal cord motion during direct laryngoscopy with their corresponding excursion tracings demonstrated near-total suppression of contractions within given stimulation "windows." These encouraging results may eventually permit selective restraint of erratic contractions involving laryngeal and other cervical musculatures in the human. PMID- 8341098 TI - Surgical pitfalls in cochlear implantation. AB - Increasing experience with cochlear implantation has led to the identification of potential surgical pitfalls: improper patient selection, poor flap design and handling, facial nerve injury, improper electrode placement, and improper seating of the receiver stimulator. Each of these areas of potential difficulty are reviewed, emphasizing methods of avoidance and management of adverse outcome. PMID- 8341099 TI - Irritative spontaneous nystagmus following intratympanic gentamicin for Meniere's disease. AB - Intratympanic aminoglycosides were first used to treat unilateral intractable Meniere's disease over 30 years ago. Gentamicin, the current drug of choice, provides excellent vertigo control with a low incidence of hearing loss. Its salutory effect results from direct damage to both the sensory neuroepithelium and the dark cells of the labyrinth. This latter effect may reverse the degree of endolymphatic hydrops. Twelve patients with unilateral Meniere's disease were treated and prospectively studied. Although further follow-up is necessary, 10 patients have complete vertigo control, while 2 remain significantly improved. Three patients developed a spontaneous "irritative" nystagmus during the early post-treatment period. This new unique finding may represent a recovery phenomenon resulting from a temporary reversible ototoxic effect in the treatment ear. Despite our patients having a somewhat higher incidence of hearing loss compared to the reported rate, the results of this treatment are encouraging. PMID- 8341100 TI - Otolaryngology manpower in the year 2010. AB - The number of otolaryngologists practicing in the future is particularly pertinent in light of the changes taking place in American medicine today. A mathematical model is presented which projects the growth of otolaryngology manpower in the year 2010, taking into consideration the age distribution of practicing otolaryngologists, death rates, and the current production of residents. This model suggests that there will be a 21% increase in the number of otolaryngologists from 1990 to 2010. The main reason for the increase is the uneven distribution of otolaryngologists by age at the present time, with 49% of otolaryngologists being less than 45 years of age. There is concern that the American medical community is populated with too many specialists and that more emphasis should be placed on training generalists. The manpower issue should be studied in more detail, and future societal needs should be determined so that a rational policy on the growth of otolaryngology can be developed. PMID- 8341101 TI - Neurologic paraneoplastic syndromes with neurotologic manifestations. AB - Evidence supports the hypothesis that autoimmune mechanisms are operational in the etiopathogenesis of certain neurologic paraneoplastic syndromes (PNSs), including paraneoplastic encephalomyelitis (PEM) and paraneoplastic cerebellar degeneration (PCD). The antibodies (Anti-Hu and Anti-Yo), the antigens (Hu and Yo), and complementary DNA clones encoding Hu and Yo, central to PEM and PCD, respectively, have been isolated. In contrast, the antigens, and antibodies if any, involved in autoimmune cochleovestibular dysfunction remain unknown. The temporal bone histopathology and neuropathology of 2 patients, 1 with PEM and 1 with PCD, who developed signs and symptoms of cochleovestibular dysfunction, are reviewed and contrasted to the literature. It is concluded that both auditory and vestibular symptomatology and pathologic alterations can be seen in association with neurologic PNSs and that studies using the antigens and antibodies involved in neurologic PNSs may provide a new perspective on the investigation of autoimmune cochleovestibular dysfunction. PMID- 8341102 TI - Morphometric analysis of the vestibular complex in the rat. AB - The characteristics of the four major vestibular nuclei and accessory cell groups in the rat have been studied in serially cut horizontal sections. Camera lucida drawings of the vestibular nuclei and their neurons were made in these sections and subjected to a computerized image analysis. The dimensions (volume and length) and the number of cells of each vestibular nucleus were obtained, as well as morphometric parameters of their neurons (cross-sectional area, maximum and minimum diameter, and shape). These parameters were statistically analyzed by comparing the cell population from different nuclei and different parts of each nucleus. Of the major nuclei, the medial, which is the largest, has the greatest number of cells, its neurons being the smallest of all the nuclei, with the size of cells decreasing in a rostrocaudal direction. In contrast, the lateral nucleus contains the fewest cells but also the largest ones. Neurons of the superior and descending nuclei are of an intermediate size and number, with a rostrocaudal decrease in the size of the descending nucleus cells. In addition, minor nuclei are identified and described in their relationship to the other structures in the brain stem. The relevant aspects of the anatomical information in regard to functional roles are reviewed. PMID- 8341103 TI - In search of missing links in otology. III. Development of a new animal model for cholesteatoma. AB - An experimental study was conducted in chinchillas regarding the pathogenesis of acquired cholesteatoma (keratoma). The placement of a chemically modified gelatin membrane from the external auditory canal to the promontory through a tympanic membrane perforation stimulated squamous epithelial cell migration. Cholesteatoma formation with the presence of keratin debris and inflammatory reactions was observed in the middle ear and anterior bulla in 53.5% of the experimental animals. These experimental findings show for the first time the presence of epithelial migration and true cholesteatoma formation in the middle ear of chinchillas in an experimental model with deliberate perforation of the tympanic membrane. Erosion of the cochlear walls was observed in areas with granulation tissue and cholesteatoma. The importance and significance of the migration of squamous epithelium and of the middle ear inflammatory reaction in the genesis of acquired cholesteatomas are discussed. PMID- 8341104 TI - Laryngeal resistance to respiratory airflow in humans. AB - Although vocal cord adduction has been observed during expiration, measurements of absolute values of resistance changes in man have not been reported in the literature. The authors measured resistance to translaryngeal respiratory airflow in inspiratory and expiratory phases of the respiratory cycle of four healthy, awake men during nasal breathing. It was found that, during quiet breathing through a decongested nose, translaryngeal resistance was 1.245 cm H2O/L per second in expiration and 0.354 cm H2O/L per second in inspiration (.005 < P < or = .01), for a percentage of approximately 25% and 50% of extrathoracic expiratory and inspiratory resistances, respectively. Voluntary hyperventilation decreased expiratory resistance, and a partial nasal obstruction abolished the statistical difference between translaryngeal inspiratory and expiratory resistance. These results are in agreement with previous observations of vocal cord movement and are consistent with an expiratory braking effect on airflow. PMID- 8341105 TI - Vestibular decruitment: an indicator of central pathology? AB - Torok studied the ratio obtained between the responses to two different heat stimulation intensities of the same temperature. A decrease in response to the strong stimulus (i.e., a diminished ratio) was called "vestibular decruitment," and was regarded as a topodiagnostic indicator of central vestibular lesion, reflecting "adaptation" or "fatigue." The authors studied the reliability of vestibular decruitment obtained by Torok's technique in the indication of central vestibular pathology. Twenty-eight normal individuals and 30 patients previously diagnosed by other methods with diffuse pathology of the central nervous system were evaluated. The results obtained show that the two stimuli used are both supraliminal and of different intensity regarding the labyrinth. In no case was vestibular recruitment obtained. In view of the high percentage of normal individuals (57.14%) who presented vestibular decruitment, we consider the latter to lack topodiagnostic value as an indicator of either central or vestibular pathology; the smaller response to the mass stimulus might be explained by the vestibular habituation phenomenon that occurs on applying Torok's technique in both normal individuals and in patients with central vestibular pathology. PMID- 8341106 TI - Effects of cyanoacrylate tissue adhesives on cartilage graft viability. AB - Cartilage graft fixation using cyanoacrylate tissue adhesives has aided in the accuracy and stability of these grafts in facial reconstructive procedures. To objectively determine how these adhesives affect cartilage viability, freshly harvested cartilage from septoplasty procedures was bonded in vitro with one of four cyanoacrylate adhesives: Histoacryl, Bucrylate, Krazy Glue, or Eastman 910 monomer. Viable chondrocytes will incorporate the sulfur-35 (35S) isotope in the synthesis of chondroitin sulfate, and is therefore a reliable test of cartilage viability. The bonded cartilage specimens were stored from 3 days to 4 weeks at 4 degrees C and then were incubated with the 35S isotope. Autoradiographs were made and the sections were counterstained. Throughout the study period, there was no statistical difference in the viability of Histoacryl-bonded specimens as compared to the controls. Specimens bonded with Bucrylate, Krazy Glue, and Eastman 910 monomer statistically demonstrated markedly less viability compared to those bonded with Histoacryl at the P = .01 level of significance. Further, the cartilage separated from these latter adhesives at the longer study times, most likely secondary to cartilage devitalization. Histoacryl optimizes graft viability as compared to these other available cyanoacrylate tissue adhesives in vitro. PMID- 8341107 TI - Direct application of basic fibroblast growth factor improves tympanic membrane perforation healing. AB - Topical application of basic fibroblast growth factor (b-FGF) on tympanic membrane (TM) perforations was studied in guinea pigs. One-millimeter simple round TM perforations or 2-mm TM perforations with medially flapped borders were performed. Either b-FGF or placebo was instilled in each ear on the day of surgery and daily thereafter. Treatment was applied either directly to the perforation or to a Gelfoam pledget over the defect. When no scaffolding material was interposed, b-FGF induced a faster healing response characterized by a hyperplastic but linear subepidermal connective tissue reaction compared to the control. When Gelfoam was interposed as a scaffold, a voluminous scar protruding into the middle ear cavity and involving the ossicles was observed in both b-FGF and control animals. Gelfoam-induced scars did not decrease after long-term observation, therefore discouraging its use. PMID- 8341108 TI - Endoscopic 'second look' mastoidoscopy to rule out residual epitympanic/mastoid cholesteatoma. AB - Endoscopic mastoidoscopy is ideally suited for patients who have undergone an intact canal wall mastoidectomy for primary acquired cholesteatoma confined to the epitympanum and mastoid. The use of an endoscopic technique significantly decreases the morbidity of the second-look procedure. Visualization of the pertinent anatomy can be reliably, quickly, and safely accomplished. PMID- 8341109 TI - Endoscopic human olfactory biopsy technique: a preliminary report. PMID- 8341110 TI - Revision surgery for Sedlacek-Kambic-Tucker epiglottic laryngoplasty. PMID- 8341111 TI - Decreasing the risk of implantation of cancer cells intraoperatively. AB - Maneuvers are suggested to decrease the likelihood of disseminating and implanting cancer cells in wounds during head and neck oncologic surgery, and thereby the risk of local-regional recurrence. These include occlusive covering of fresh tracheotomy sites and areas of skin ulceration, excising the primary tumor before performing neck dissection(s) to avoid contamination of uninvolved tissue planes, irrigation of the field with hypotonic solution after removal of the primary tumor, and using clean instruments and apparel when moving between anatomical sites (e.g., donor flaps/grafts, skull base extensions, percutaneous or standard gastrostomies, etc.). PMID- 8341112 TI - In leprosy the presence of mycobacteria in the nerve is an essential factor in the cycle and spectrum of Mycobacterium leprae infection. AB - A total of 220 untreated leprosy patients who underwent parallel skin and nerve biopsies are included in this study, which is intended to evaluate the extent of previously reported differences in bacillary load between skin and nerve lesions in leprosy and to describe the response of peripheral blood lymphocytes to Mycobacterium leprae antigens in such patients. In 161 patients out of the 220, the skin and nerve biopsies were diagnostic for leprosy. When patients were grouped according their skin and nerve lesions, the 3 groups observed were (1) paucibacillary skin and nerve lesions; (2) multibacillary skin and nerve lesions, and (3) paucibacillary skin and multibacillary nerve lesions. There was no observation of a group of patients with multibacillary skin and paucibacillary nerve lesions. In all patients with multibacillary nerve lesions, regardless of the type of skin lesions, a low response of peripheral blood lymphocytes to M. leprae was consistently noted. These results suggest that the bacillary load in the nerve is certainly one of the factors determining the immunological spectrum observed in leprosy. PMID- 8341113 TI - Concurrent skin and nerve histology in leprosy and its role in the classification of leprosy. AB - Concurrent skin and nerve histology was evaluated in 60 leprosy patients (25 BT, 28 BL and 7 LL). The twin aims were to study the comparative histology and the usefulness of nerve histology in the classification of the disease. In BT patients, clinical and histological classification was in agreement in 11 (44%) skin and 17 (68%) nerve biopsies. Concurrent skin and nerve histology was in consonance in 14 (56%) BT patients, while in 6 (24%) patients, only nerve histology was helpful in the classification of the disease, the skin histology being non-specific. Nerve histology was classified as BL in 3 (12%) BT patients, the skin histology was non-specific. In the BL group, the histology of 23 (82.4%) nerve biopsies correlated with the clinical classification, in contrast to skin histology which correlated with clinical assessment in 19 (68%) patients only. In the LL patients, the histology of nerve correlated with the clinical classification in 5 patients (71.4%), compared to histology of the skin in 4 (57%) patients only. The GF was higher in the nerves than in the skin throughout the leprosy spectrum (BT, BL, LL); the difference was, however, marginal in BL leprosy. The average bacteriological index (BI) was higher in nerves (4+) compared to that of skin histology and slit skin smears (3+) in BL leprosy. There was, however, no difference in the BI of the slit skin smears, skin and nerve biopsies in lepromatous leprosy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341114 TI - Pilot study to determine acceptability and ability of heat-killed Mycobacterium leprae plus BCG (HKML+BCG) vaccine to induce skin test conversion. AB - Although local reactions, including erythema, induration and ulcers, appeared in every patient after the injection of the combined HKML+BCG vaccine, they were accepted by the patients. There was no tendency for the local reaction to become aggravated after repeated vaccination. However, systemic reactions, mainly iridocyclitis and complaint of numbness of the fingers and toes, became quite common after the 5th vaccination and therefore significantly reduced the acceptability of vaccine by injection. It seems that repeated vaccination might activate the iridocyclitis, but the relationship between the complaint of numbness and vaccination has not been well established. Neither typical ENL nor reversal reaction had been observed throughout the trial. A significant proportion of patients converted to SMLA positivity after repeated vaccination. However, it seems the positive status was not stable as many of them reverted to negative after the following vaccination. After the 7th vaccination, the positive conversion rate to SMLA-I was 45% and to SMLA-II was 35%. After the 8th vaccination, 66.7% of patients converted to Mitsuda reaction positive, which has been confirmed by histopathological examination. Nevertheless, further follow-up is required in order to determine whether or not such conversion will be of a long duration. The reactions to SMLA-I and SMLA-II were associated but only correlated at a moderate level. Overall, the positive conversion rate to SMLA-I was significantly higher than that to SMLA-II after repeated vaccination. Neither the early reaction nor the late (Mitsuda) reaction of the lepromin test were correlated to either SMLA reaction. The repeated vaccination of HKML+BCG vaccine did not affect the weakly-positive anti-PGL-1 Mycobacterium leprae antibody level seen in the skin-smear negative lepromatous patients participating in this study. PMID- 8341115 TI - Survey for secondary dapsone and rifampicin resistance in Cuba. AB - A total of 1211 Cuban multibacillary leprosy patients treated for at least 5 years were clinically and bacteriologically examined. They were being treated according to a 2-phase monotherapy regimen with RMP first and DADDS afterwards. On skin-smear examination 50 patients were found positive, of which 9 showed a BI of 3+ or higher at any site. With regard to the clinical status the only cases found with clinical signs of relapse were 5 out of 7 long-standing patients with BI of 4+ and 5+. A 6th patient of this high BI group who showed a good clinical condition, except for a heavy infiltration of both earlobes, was receiving a second RMP course when examined and biopsied for this research. These 9 patients were biopsied and susceptibility tests to RMP and DDS performed. The results showed that in 1 case the Mycobacterium leprae were resistant to both drugs; the organisms from 2 other patients were susceptible to RMP but low-grade resistant to DDS. Those from another patient were susceptible to RMP and fully resistant to DDS. In 3 other cases the bacilli did not multiply in any of the mice but 1 of these strains was from the patient taking a second RMP course, therefore this strain might also be susceptible to RMP and resistant to DDS. In the last 2 cases multiplication was only observed in 2 of the controls and in 1 of the 0.0001% DDS treated mice; therefore, these experiments were not conclusive, and the AFB recovered were inoculated into fresh mice to repeat the tests but these failed to multiply. PMID- 8341116 TI - Efficacy and safety of multidrug therapy in paucibacillary leprosy in Singapore. AB - A total of 49 patients with paucibacillary leprosy (PB) who completed multidrug therapy (MDT) between 1985 and 1990 were analysed retrospectively for efficacy and complications; 20 (40.8%) patients had borderline-tuberculoid (BT), 13 (26.5%) had tuberculoid (TT), 1 (2.1%) had indeterminate (I) and 15 (30.0%) had pure neural (N) leprosy; 26 patients (76.5% of 34 non-neural leprosy) were skin biopsied for histological cure before MDT was stopped. Of these 26 patients, 19 had histological clearance at 6 months while the remaining 7 cleared beyond 1 year (18-36 months). The remaining 8 non-neural patients who refused rebiopsy had MDT for 6-8 months and the MDT was stopped when there was clinical clearance. Of the 15 neural (N) leprosy patients, 11 were given MDT for 6 months while the rest had 12-18 months of treatment; 1 patient with neural leprosy, who was treated for 6 months, relapsed with BT leprosy 18 months post-treatment. There were few complications among the 49 patients-4 (8.2%) patients developed reaction to dapsone, 1 (2.0%) had the dapsone syndrome, 2 (4.1%) had haemolytic anaemia and 1 (2.0%) had dapsone hepatitis; 7 (14.3%) patients had type I reaction. PMID- 8341117 TI - An epidemiological survey of deformities and disabilities among 14,257 cases of leprosy in 11 counties. AB - This study was planned and conducted in Yang Zhou Prefecture, covering 11 counties that were formerly areas with a high prevalence of leprosy. Out of 14,257 leprosy patients, 8122 (56.97%) cases with deformities and disabilities were found. The disability rate is much higher in patients with MB leprosy (81.15%) than in PB leprosy (53.04%). The statistical data and the type of deformities and disabilities are presented. The influences of various host factors and disease factor which cause disability and deformity are discussed. PMID- 8341118 TI - Inventory of skin smear practices in 6 leprosy control programmes in Nigeria. AB - A study of slit skin smear (SSS) examination practices in 6 Nigerian Leprosy Control Programmes was undertaken to assess the quality of smearing, staining and reading. Results indicated that the standard of SSS practices fall below the ideal. There is a great need for training as well as supervision and support of laboratory staff if this deplorable situation is to be improved. PMID- 8341119 TI - Borderline-tuberculoid relapse in lepromatous leprosy. AB - We report details of 2 patients who had been treated for a long time by dapsone monotherapy and who had remained smear negative for over 10 years, but were found to have relapsed with borderline-tuberculoid (BT) leprosy. PMID- 8341120 TI - Divorce among Saudi female leprotic patients: an experience at Ibn Sina Hospital. PMID- 8341121 TI - Tuberculoid relapse in lepromatous leprosy. PMID- 8341122 TI - Disappointing experiences with blister-calendar packs. PMID- 8341123 TI - Comment: nasal myiasis in leprosy. PMID- 8341124 TI - Reply: treatment of smear negative MB patients who had received previous dapsone monotherapy. PMID- 8341125 TI - Current global situation on the HIV/AIDS pandemic: WHO. PMID- 8341126 TI - Leprosy control through general health services and/or combined programmes. PMID- 8341127 TI - Human immunodeficiency virus and leprosy. AB - In summary, clinical leprosy does not appear to be more frequent in HIV-positive than in HIV-negative people in areas where both infections are endemic. There is no evidence that the paucibacillary to multibacillary distribution of patients is altered by HIV infection. There are reports that neuritis is more severe in co infected people, and that reversal reactions (or, at least, new lesions) may be more frequent after therapy; but these reports are either poorly documented or poorly controlled. In several ways, this lack of expected leprosy is similar to the patterns of other low-virulent infections in HIV-positive patients in the tropics, such as MAC infection, Pneumocystis carinii and cytomegalovirus infection. Despite the presence of the agents in the environment and/or in the human host, they are infrequently encountered clinicopathologically. This is in marked contrast to their importance in industrialized countries. One explanation, as yet unproven, is that HIV-positive patients in the tropics do not live long enough in states of severe immunosuppression to develop these infections. Perhaps the same applies to M. leprae infection, whose incubation period can be measured in decades and whose clinical course may evolve over years, in contrast to the common reactivation of latent, virulent M. tuberculosis infection with its high morbidity. There may also be an analogy between leprosy and infection with Plasmodium falciparum, Strongyloides stercoralis and Entamoeba histolytica: these infections are controlled (or at least influenced) by cell-mediated immunity and, theoretically, should be more frequent in HIV-positive people than HIV-negatives. In fact they are not, and leprosy may be regarded as another 'missing infection in AIDS'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341128 TI - Further evidence for the involvement of prolactin in the inflammatory response. AB - The pro-inflammatory activity of prolactin (PRL) was clearly demonstrated in our previous research on rat paw oedema. In the present study we report our results on the activity of PRL on other animal models of acute and chronic inflammation. Repeated administration of ovine PRL provoked a significant increase in the inflammatory parameters in experimental carrageenan pleurisy (leukocytes number and prostaglandin E2 concentration in the exudate). A pro-inflammatory effect was also present after a hyperprolactinaemia induced by pituitary gland graft. Moreover, the inflammatory response to polyester sponge implantation was significantly potentiated by oPRL, whereas the hormone was completely inactive on cotton pellet granuloma test. A possible involvement of prostaglandins in the pro inflammatory activity of PRL is suggested. PMID- 8341129 TI - Analysis of vasocontractile responses to endothelin-1 in rabbit retinal vessels using an ETA receptor antagonist and an ETB receptor agonist. AB - To study the role of endothelin receptor subtypes in rabbit retinal arteries, endothelin-1 (ET-1)-induced vasoconstriction was analyzed using the ETA receptor antagonist BQ-123 and the ETB receptor agonist BQ-3020. A cumulative injection of ET-1 (1 approximately 100 pmole) into the posterior vitreous body in anesthetized rabbits caused dose-dependent vasoconstriction in the retinal arteries, and ultimately caused complete obstruction. Fifteen minutes after BQ-123 (1 mumole) was injected into the posterior vitreous body, the dose-response curve of ET-1 was significantly shifted to the right. Intravitreal injection of BQ-3020 caused a significant retinal vasoconstriction only at the highest dose (1000 pmole). Therefore, in rabbit retinal arteries, ET-1-induced vasoconstriction appears to be mediated mainly through ETA receptors. PMID- 8341130 TI - Concanavalin A enhances ATP resynthesis via de novo pathway in postischemic rat hearts. AB - Acute post-ischemic cardiac failure was studied in isolated rat hearts. Xylitol, glutamine, aspartic acid and glycine were added during reperfusion, resulting in no inotropic effect. Concanavalin A had a moderate inotropic effect. When concanavalin A added with xylitol, glutamine, aspartic acid and glycine, a rapid recovery of myocardial function and high-energy phosphate was achieved. PMID- 8341131 TI - Neuroendocrine probes of serotonergic function: a critical review. AB - Neuroendocrine probes of serotonergic function are based on the premise that serotonin (5-HT) exhibits an excitory influence on the release of certain anterior pituitary hormones and that the extent of release of these hormones following a challenge with a 5-HT agonist would provide an index of central 5-HT activity. This paper critically reviews studies published to date on healthy volunteers to assess the validity of tests of serotonergic function. Using standardized criteria, it is concluded that although extensive data is available on 5-HT-neuroendocrine probes, there is no test that is currently available that would fulfil all the proposed requirements for a test to be acceptable, although ipsapirone, m-chlorophenylpiperazine (m-CPP), and possibly fenfluramine challenge tests come very close. The rapid development and availability of more specific and stereo-selective 5-HT agonists/antagonists seem to indicate that it will not be too long before a valid neuroendocrine test for the assessment of serotonergic function emerges. PMID- 8341132 TI - Phosphoramidon-sensitive endothelin converting enzyme in cultured vascular smooth muscle cells converts big endothelin-3 to endothelin-3. AB - Incubation of big endothelin-3 (big ET-3, 1-41) with the membrane fraction obtained from cultured vascular smooth muscle cells (VSMCs) resulted in time dependent increases in immunoreactive-ET (IR-ET), which were suppressed by phosphoramidon. Analysis of the incubation mixture by reverse-phase high performance liquid chromatography (RP-HPLC) confirmed that the IR-ET was due to the mature ET-3 (1-21). ET-1 (1-21) generated during incubation of big ET-1 (1 39) with the membrane fraction was markedly suppressed by the addition of big ET 3 into the incubation mixture. When the cultured VSMCs were incubated with big ET 3, a conversion to the mature ET-3 was observed. This ET-3 generation from exogenously applied big ET-3 was also suppressed by phosphoramidon. We conclude that the phosphoramidon-sensitive ET converting enzyme in VSMCs converts big ET-1 and big ET-3 to their mature form. PMID- 8341133 TI - Effect of systemic interleukin-3 administration on epithelial cell proliferation in mouse intestine. AB - The effect of interleukin-3 (IL-3) on the crypt cell production rate (CCPR) in the intestine of mice was studied using a stathmokinetic technique combined with crypt microdissection. Interleukin-3 (0.71 micrograms/injection) was administered subcutaneously (s.c.) as two injections per day for 7 successive days and small mucosal pieces (duodenum, jejunum, ileum and colon) removed at necropsy were organ cultured in the presence of the metaphase arrest agent vincristine sulfate for two hours. The number of metaphases was enumerated in dissected crypts and CCPR calculated. The results demonstrated that the CCPR was significantly increased in all mucosal segments in the IL-3 treated animals compared to saline injected controls. These results suggest that the growth promoting properties of IL-3 are not restricted to hematopoietic cells when used in vivo and may directly or indirectly increase epithelial cell turnover in gut mucosa. PMID- 8341134 TI - Delayed matching-to-sample performance during a double-blind trial of tacrine (THA) and lecithin in patients with Alzheimer's disease. AB - During a double blind, inpatient-outpatient study of THA (tacrine) and lecithin in Alzheimer's disease, data on a laboratory-based delayed-matching-to-sample (DMS) test was collected on six of 10 subjects. DMS measures proved more sensitive to drug effects than clinical measures of cognitive performance. Both clinical and DMS measures suggest that patients with mild to moderate impairment are more likely to show modest improvement in performance than advanced cases. Outcome measures are related to possible mechanisms of attention and memory. PMID- 8341135 TI - Influence of calcium on the release of endogenous adenosine from spinal cord synaptosomes. AB - Intrathecal administration of Ca2+ has been shown to produce antinociception which is thought to be partially mediated by the release of adenosine. In the present study we have examined directly the effects of varying Ca2+ concentrations on the release of endogenous adenosine, measured by HPLC with fluorescence detection, from rat spinal cord synaptosomes. Although increasing the concentration of extracellular Ca2+ reduces the total amount of adenosine detected extrasynaptosomally, the component derived from the release of adenosine per se is actually augmented. This release of adenosine occurs from dorsal but not ventral spinal cord synaptosomes and appears to originate from capsaicin sensitive nerve terminals. The Ca2+ ionophore A23187 also releases adenosine, but this release is due to the extrasynaptosomal conversion of released nucleotide(s) to adenosine, as it is markedly reduced by ecto-5'-nucleotidase inhibitors. Release of adenosine by A23187 occurs from both the dorsal and ventral spinal cord, and is not capsaicin-sensitive. Ethanol, used as a vehicle for the ionophore, releases adenosine which is a mixture of adenosine and nucleotide from both dorsal and ventral spinal cord synaptosomes. These observations provide direct support for behavioural studies which demonstrate that methylxanthines block antinociception produced by intrathecal administration of Ca2+. PMID- 8341136 TI - The adenosine kinase inhibitor, 5-iodotubercidin, is not protective against cerebral ischemic injury in the gerbil. AB - 5-Iodotubercidin is a potent inhibitor of the enzyme adenosine kinase. It has a recognized ability to enhance interstitial fluid levels of the cerebroprotective purine, adenosine, in the hypoxic brain, and an anticonvulsant action, which is thought to be a consequence of its ability to increase extracellular adenosine levels. 5-Iodotubercidin (1 mg/kg, i.p.) was therefore tested for its ability to reduce cerebral ischemic injury in a gerbil model. Unanesthetized gerbils were subjected to a 5 min period of bilateral carotid artery occlusion and then maintained in an environmental chamber at 30 degrees C for 5 hr to counteract the hypothermia-inducing action of 5-iodotubercidin. As estimated from the extent of the increases in locomotor activity and the magnitude of hippocampal CAI layer pyramidal cell loss, 5-iodotubercidin (1 mg/kg) failed to have a cerebroprotective effect against ischemic injury. PMID- 8341138 TI - SDZ CO 611: a highly potent glycated analog of somatostatin with improved oral activity. AB - To obtain orally active octreotide (Sandostatin, SMS 201-995) analogs a new class of glycated somatostatin derivatives were synthesized by the Amadori reaction (Maillard reaction). The synthesis, chemical and biological characterization of a series of new compounds is described. These oligopeptides bind with high affinity to somatostatin receptors and retain full biological activity. Whereas generally polypeptide hormones are almost completely inactive after oral administration, we report here for the first time that these analogs show remarkably high activity by the oral route. Thus for example SDZ CO 611, the D(+)-maltose Amadori derivative of octreotide, has about 10 times higher oral effect bioavailability than octreotide while maintaining the selectivity, metabolic stability and long duration of action of the parent compound. PMID- 8341137 TI - The phenytoin metabolite p-HPPH upregulates prostaglandin biosynthesis in human gingival fibroblasts challenged to interleukin-1. AB - The effects of and interactions between the major phenytoin (PHT) metabolite 5 parahydroxyphenyl-5-phenylhydantoin (p-HPPH) and interleukin-1 (IL-1 alpha, IL-1 beta) or tumor necrosis factor alpha (TNF alpha) on prostaglandin biosynthesis in human gingival fibroblasts were studied. IL-1 alpha, IL-1 beta and TNF alpha, dose-dependently, stimulated PGE2 formation in gingival fibroblasts. The metabolite, p-HPPH (1.2-2.4 micrograms/ml), did not induce PGE2 formation itself but potentiated IL-1 alpha and IL1 beta induced PGE2 formation in the gingival fibroblasts in a manner dependent on the concentration of both IL-1 and p-HPPH. The metabolite also stimulated IL-1 induced formation of 6-Keto PGF1 alpha, the stable breakdown product of PGI2, in a dose dependent manner. IL-1 beta induces release of [3H]-arachidonic acid ([3H]-AA) from prelabelled fibroblasts, which was potentiated by p-HPPH (> or = 1.2 micrograms/ml). TNF alpha (> or = 1 ng/ml) significantly stimulated the biosynthesis of PGE2 by a process that was also potentiated by p-HPPH. Addition of exogenous, unlabelled AA (10 microM) caused an increase of PGE2 formation in the fibroblasts that was not potentiated by p-HPPH (1.6 micrograms/ml). The results indicate that treatment with p-HPPH results in upregulation of prostaglandin synthesis in gingival fibroblasts challenged to IL 1 or TNF alpha at the level of phospholipase A2. PMID- 8341139 TI - Catastrophic visual loss due to Cryptococcus neoformans meningitis. AB - We have reviewed our experience with 17 of our own patients with cryptococcal meningitis and 32 cases from the literature. Although this complication is an uncommon event, patients with cryptococcal meningitis may develop visual loss in the absence of other ocular lesions (endophthalmitis or cryptococcomas in the visual pathway) that could explain the visual symptoms. There are 2 distinct patterns of visual loss: rapid visual loss and slow visual loss. Rapid visual loss is characterized by onset of profound visual loss over a period as short as 12 hours before or early in the course of therapy and a clinical syndrome that is strongly suggestive of optic neuritis. Direct invasion of the optic nerve by C. neoformans is demonstrated by cases in this and other reports. Slow visual loss is characterized by slow but progressive visual loss which typically begins later during therapy and may be due to the effects of increased intracranial pressure. While the initial deficit may be mild, patients with slow visual loss can progress to severe visual loss over weeks to months. The only factors that appear to predict either pattern of visual loss are the presence of papilledema, an elevated CSF opening pressure, and a positive CSF India ink preparation. In the 25 visual loss patients for whom data were available for all 3 items, 10 (40%) were positive for all 3, as opposed to only 4 of 114 (3.5%) from a reference group of cryptococcal meningitis patients without visual loss (p < 0.00001). The only therapeutic measures with any degree of consistent success were those directed at reducing intracranial pressure. When begun early and used aggressively, such therapy halted and sometimes even reversed the course of visual loss, particularly in the slow visual loss group. Corticosteroids did not appear to be of value in the small number of patients who received them. PMID- 8341140 TI - Clinical expression of systemic lupus erythematosus in patients with C4A deficiency. AB - We studied 121 patients with systemic lupus erythematosus (SLE), of whom 119 were complement typed. Both black and white patients with SLE were more likely than racially matched controls to have a C4A null allotype. Patients with homozygous C4A deficiency had less proteinuria than other patients (p = 0.02) and both homozygous and heterozygous C4A-deficient patients (p = 0.05) had fewer seizures than other patients. Anti-dsDNA, anti-Sm, anti-Ro, and anticardiolipin antibodies were less common in patients with homozygous C4A deficiency, with heterozygous C4A-deficient patients intermediate in frequency between homozygous C4A-deficient and normal patients with SLE. Both homozygous and heterozygous C4A-deficient patients (p < 0.005) had higher C3 levels than other patients, and heterozygous C4A-deficient patients had higher, not lower, C4 levels (p < 0.002), compared with non-C4A-deficient patients. C4A gene deletion was found in 23.4% of patients. C4A gene deletion was associated with subacute cutaneous lupus erythematosus (p = 0.04) and Sjogren syndrome (p = 0.02) in patients with SLE. Both anti-dsDNA (p = 0.04) and anticardiolipin (p = 0.04) were found less frequently in patients with C4A gene deletion. Patients with C4A gene deletion had lower C4 levels than patients with C4A deficiency from other mechanisms. We conclude that the presence of 1 or 2 C4A null allotypes and the presence of a C4A gene deletion identify subgroups of patients with SLE that differ in clinical, laboratory, and autoantibody characteristics from other patients with SLE. PMID- 8341141 TI - Kaposi sarcoma. PMID- 8341142 TI - The etiology of rheumatic fever: A review of theories and evidence. 1949. PMID- 8341143 TI - The etiology of rheumatic fever: a review of theories and evidence. 1949. PMID- 8341144 TI - The clinical patterns of acute rheumatic fever: a reappraisal. 1962. PMID- 8341145 TI - Preventive medical informatics for office practice. PMID- 8341146 TI - Checkup interval and cancers in automated multiphasic health testing and services. AB - The purpose of this study was to disclose which types of cancer and how many persons with cancer were detected among the AMHTS examinees of our AMHTS center by using the hospital information retrieval system, and to study the relationship between cancer and the number of examinees, checkup intervals, and frequency in AMHTS. The examinees who had checkups more than twice were divided into three groups based on their checkup intervals: within one year, one to two years, and over two years. The relationship between cancer ratios and checkup intervals was evaluated in each group of examinees. In those having checkups within one year and from one to two years the cancer rate was 2.9 patients per 1,000 persons. However, in those having checkups after a two-year period or longer, the cancer rate was 4.3, clearly greater than the rate of the other two groups. PMID- 8341147 TI - Repeated multiphasic screening examinations: evaluating the process. AB - There are sound clinical and epidemiological reasons to promote and emphasize early detection efforts and disease prevention services. A large body of scientific literature supports the notion that detection and intervention early in the course of many diseases is beneficial both to the afflicted individual and to society at large. Several publications deal with the evaluation of multiphasic screening examinations (MSE) as a tool for simultaneous early detection and prevention of multiple risk factors and various diseases. Usually, this technology is evaluated based on data from a single (cross-sectional) comprehensive screening study. However, frequently MSE are performed periodically, resulting in repeated test results of the same individuals. The health impact of such repeated (longitudinal) MSE has not been studied extensively. Similarly, many of the unique theoretical, technical, and epidemiological features characteristic of consecutive (periodical) comprehensive screening examinations are not well-documented. The purpose of this study was to compare the test results of two MSE, performed 3.5 years apart, in order to demonstrate certain characteristics of multiphasic health testing (MHT) technology related to repeated (longitudinal) multiphasic examination of the same individuals. PMID- 8341148 TI - Economic evaluation of a Ninngen-dokku (medical checkup). AB - An economic evaluation of a medical checkup center (Ninngen-dokku, "human dry dock") was conducted from two perspectives: the cost for cancer checkup, and the cost for medical treatment after a diagnosis was obtained. We studied the cost of diagnosing cancer, compared with the cost required when cancer of an individual organ was detected through mass health testing, and studied the economics of a Ninngen-dokku according to Kawai's method of medical judgment. Assuming that the cost of death is more than the cost of saving the lives of persons who undergo the Ninngen-dokku, the Ninngen-dokku will be affordable. In the group undergoing the Ninngen-dokku compared with the group which did not, the estimated cost of medical treatment was reduced. The Ninngen-dokku carries advantages that cannot be quantified in financial terms; therefore, a multi-layered economic analysis of the Ninngen-dokku was required. PMID- 8341149 TI - Fitness in a U.K. screening sample--a comparison with the Canadian population. AB - Fitness measurements were compared from approximately 12,000 men and 5,000 women attending the BUPA Health Screening Centre, London, with published Canadian levels. The mean (+/- SD) predicted VO2-max values in the BUPA group were 35.1 (+/- 9.2) and 30.0 (+/- 8.4) ml/kg/min for men and women aged 15-64 years, respectively. These compare with means of 44.1 and 34.3 in men and women of the same age in Canada. A comparison of flexibility measurements showed that in all age groups the BUPA subjects were less flexible than their Canadian counterparts, on average 28.7% and 25.1% lower for men and women, respectively. Comparison of grip strength showed BUPA values to be on average 8.1% lower in men and 9.5% lower in women than the Canadian levels. Analysis of variance showed that the fitness measurements reflect the recorded physical activity in the BUPA sample, and in particular the predicted VO2-max and flexibility exhibit linear relationships with age and exercise levels. PMID- 8341150 TI - Heart rate response to exercise in normal women. AB - Heart rate is known to increase under the influence of increased sympathetic stimulation rates during exertion or stress. Few data are available regarding the rate response to exercise near the fatigue limit, for normal women. The effects on heart rate were studied of fatigue limiting exercise in 87 asymptomatic, normal female subjects employing a bicycle ergometer exercise protocol. The heart rate response to imposed exercise power closely followed a monotonic increasing, negative exponential function. Different age groups followed the same form of function but differed in parameter values. Group fitting was useful to develop parameters with which one group may be compared to another, establish referent ranges, and gain insight into cardiovascular models of exercise physiology. PMID- 8341151 TI - Athletes as health testing examinees. AB - Health-testing examination data of 91 male and 54 female athletes were studied, together with age-matched controls, on serum biochemistry, ECG findings, hematology, and some data on gynecological physiology. Analysis of serum biochemical values revealed statistically significant differences in 14 of 18 routine test items as compared with the age-matched controls. In ECG findings, the combination of bradycardia and left ventricular hypertrophy was most frequently found in male athletes, whereas that of bradycardia and sinus arrhythmia was observed predominantly in female athletes. The incidence of anemia and menstrual dysfunction was higher in female athletes than in controls, especially in the basketball team. In the same team, a high rate of deviant ECG records and a different distribution of the age at menarche were also observed. PMID- 8341152 TI - Significant left ventricular hypertrophy in subjects with normal resting pressures but exaggerated pressure response during light exertion. AB - Concentric left ventricular hypertrophy (LVH) frequently occurs in subjects with normal resting systolic and diastolic pressures (SP and DP, respectively). LVH in this normotensive-hypertrophic group (NH) may be due to an abnormally exaggerated pressure response to exercise. The SP and DP responses to exercise were studied in 130 subjects free from coronary artery disease or cardiomyopathy. The NH subjects (n = 35) had normal resting pressure (SP < or = 140 and DP < or = 85 mmHg) and increased LV wall thickness (T) by echocardiography (T > 1.1 cm). A normal control group (NN) (n = 57) and a hypertensive control group (HH) (n = 23) were simultaneously evaluated. The original groups, subgroups censored for age and weight, and matched-pair subgroups demonstrated greater exercise SP for NH than for NN (p < 0.005). Moreover, the rate of SP increase with exercise was greater for NH than for NN or HH (p < 0.05). Hence, an exaggerated exercise SP response may have been the stimulus for LVH in these NH subjects. PMID- 8341153 TI - Serum lipid values and age in healthy women: a preliminary report on cholesterol. AB - In a 20-year prospective study of the influence of lifestyle and age on health parameters in men's and women's serum cholesterol, triglycerides and high density and low density lipoproteins were measured periodically to determine each person's longitudinal profile. The accumulated data for 1008 women of 20 to 70 years is averaged by five-year age brackets. Scatter plots and simple regression of these five-year group means for ages 20 to 45 years, reveals a gradual increase in serum cholesterol, increasing from 176 mg/dl to 196 with a slope of 0.61 mg/dl per year. Between ages 45 and 70, the slope increases substantially to 1.91 mg/dl per year, and the five-year group means rise from 196 at age 45 to 239 at age 70 in rather uniform increments. The data have been analyzed for the other lipids and the relationship to estrogen replacement, nutritional, and exercise habits. PMID- 8341154 TI - Benefits and risks of combined oral contraceptives. AB - The use of combined oral contraceptives carries a number of well-established major non-contraceptive benefits. Of these, the most important protective effects are suppression of the risk of epithelial cancer of the ovary and cancer of the endometrium. Also of great importance is a reduction in the risk of pelvic inflammatory disease. Needless to say, there are also some established risks of combined oral contraceptives. The most important of these are the vascular ones, comprising effects on acute myocardial infarction, thrombotic stroke, haemorrhagic stroke, and venous thrombosis and embolism. Possible risks which are still under evaluation include an adverse effect on breast cancer and, likewise, on carcinoma of the cervix. More information is needed about both these conditions. A number of authors have provided analyses of varying degrees of complexity in which they have attempted to weigh the benefits and risks of combined oral contraceptives. Results from some of these studies are presented in the paper. On the whole, the findings are reasonably reassuring. PMID- 8341155 TI - Defining normality--art or science? AB - The problem of defining normality, and in particular the establishment of reference ranges, is discussed. A so-called "objective" method of determining such ranges is described. It is suggested, however, that all currently used methods for defining "normal" ranges rely ultimately on a subjective choice. We propose the use of "How Often That Happens" (HOTH) graphs as an alternative to the conventional reference range. Such graphs show the frequency of results at least as extreme as any observed value. We have used such graphs, along with computer simulation models, in an attempt to describe how the frequency distribution of a given parameter changes as a population ages. Finally, an analogy is drawn between the states of "health", "illness" and "death", and the attractors which arise in non-linear dynamic systems. We conclude that the definition of normality is in fact more of an art than a science. PMID- 8341156 TI - Probability graphics support for medical reasoning. AB - Graphic displays of data from clinical observations and laboratory testing provide important support to the health practitioner in managing an increasing amount of complex information. A graphic display program is described that preserves much of the context of data that is important to their evaluation, and that maintains a sense of the strength of the signal when aberrant data are encountered. PMID- 8341157 TI - Bone density, biochemistry and life-style. AB - We have assessed the relationship between bone density, biochemistry and life style factors in a cross-sectional study of 434 pre- and 357 postmenopausal women. Bone-mineral content (BMC) was measured in the non-dominant forearm using single-photon densitometry. Bone mass was corrected for bone size (BMC2) in a sub set of 263 subjects. Correlation statistics and multiple regression analyses were used to identify physical and biochemical measurements that could be used to best predict BMC or BMC2. These were combined with lifestyle factors, using multiple logistic regression analysis, to identify women at risk of low bone density. Cut off values were taken as the 5th percentile of the bone density distributions in pre-menopausal women. In postmenopausal women, using BMC2 values to define "risk", and using age, creatinine, alkaline phosphatase, thyroxine treatment, and calcium supplementation as predictors, a sensitivity of 73% and a specificity of 95% were achieved. Such a model may be of use as a "first pass" screening test for osteoporosis. PMID- 8341158 TI - Criteria for screening diabetes mellitus using serum fructosamine level and fasting plasma glucose level. The Japanese Society of Multiphasic Health Testing and Services (JMHT), Fructosamine Working Committee. AB - A screening method using serum fructosamine level and the fasting plasma glucose level was used for screening patients with diabetes mellitus. The criteria for positive tests recommended by the Japanese Society of Multiphasic Health Testing and Services were evaluated. It was found that levels for the serum fructosamine of 290 mumol/l or higher (or, for the fasting plasma glucose of 110 mg/dl or higher) agreed with the standard oral glucose tolerance test in identifying patients with diabetes mellitus in 96.7% of cases, and the serum fructosamine test was simpler and less expensive. PMID- 8341159 TI - George Zur Williams, MD, DSc, FCAP, FASCP--biographical description. PMID- 8341160 TI - HEALTH WATCH: health promotion and disease prevention in primary care. AB - HEALTH WATCH, a longitudinal prospective study of healthy aging, was designed to characterize a healthy population of 2,200 men and women, ages 20-80 years in 1970. Biochemical, hematological, and physiological tests are performed annually over three weekly visits, combined with a self-administered HEALTH WATCH questionnaire to measure health status and behaviors in seven areas (with over 1,330 variables). In 1988, the HEALTH WATCH study was modified to assess characteristics of an oldest old "productive aging" cohort in Kauai, Hawaii. Nutrition, physical activity, extended family, and spirituality were found to be major health determinants. During 1989 to 1991 a controlled intervention study (ten local primary care physicians and their patients, aged 65-89 years) was completed in the Sun Cities, Arizona. These studies provide evidence that primary care physicians can promote positive health outcomes in patients of any chronological age and baseline health status through active healthy aging interventions. PMID- 8341161 TI - Cerebral and functional aging: first results on prevalence and incidence of the Paquid cohort. AB - Paquid is an interdisciplinary study designed to investigate cerebral and functional aging. A cohort of 3,777 community residents living in two administrative areas of South-Western France was selected. A standardized questionnaire was administered at home by trained psychologists. The same procedure was applied one and three years after the baseline data collection. The identification of demented subjects was made with a two-step procedure. The first step is a systematic screening by the psychologists using the DSM-III criteria for dementia. Subjects who fulfilled the DSM-III criteria were examined by a neurologist. Diagnosis of dementia is confirmed according to the NINCDS-ADRDA criteria. The Paquid cohort is complemented by a random sample of 357 institutionalized subjects. First results of prevalence and incidence rates show an exponential increase of dementia with age. PMID- 8341162 TI - Physiological age-related changes: cross-sectional and longitudinal studies. AB - Physiological age-related changes were investigated by cross-sectional and longitudinal studies. The data of the study were derived from volunteers admitted to the Gerontology Center in Budapest. In the follow-up study 864 subjects took part, and in the cross-sectional study 2,281 individuals. The 20-year longitudinal study and the cross-sectional examination showed that from a clinical standpoint the most important observation is that several biochemical data do not change with age. No changes were found in the values in erythrocyte sedimentation, hemoglobin, hematocrit, serum total protein, albumin, liver function, glucose, creatinine, triglyceride, and HDL-cholesterol levels. Changes were observed in the levels of HDL-cholesterol, immunoglobulins, rheumatoid factors, antinuclear factors, morphology of lymphocytes, serum TSH and T3 concentration, and systolic blood pressures. PMID- 8341163 TI - The role of genetics in defining reference values and health status. AB - Since its establishment, the Center for Preventive Medicine in Vandoeuvre-les Nancy, France, performed specific studies on healthy humans, and its approach was very useful for defining reference values. Prevention should extend its interest to chronic diseases. The majority of important adult disorders are partially genetically determined. Genetic markers are also useful as exclusion or as partition criteria in the production of reference values. Results are presented that were obtained for apolipoproteins E, B and AIV, frequencies of these polymorphisms in the Lorraine population, and relationships between these polymorphisms and lipid metabolism-related parameters. Health checkup centers, in particular those involved in family screening, are well suited for resembling many data concerning environmental factors: tobacco consumption, alimentation habits, or alcohol and drug consumption. Simultaneous determination of genetic markers could allow the determination of an individual's susceptibility or resistance to developing a disease and to prepare a preventive action. PMID- 8341164 TI - Health-risk appraisal applied to ordinary AMHTS. AB - The main purpose of an automatic health testing system (AMHTS) has changed from early detection to primary prevention. Health-risk appraisal is now widely available as a tool of health education aiming at the modification of unhealthy lifestyles. However, the opportunity to offer appropriate health education was less frequent for those who had no particular findings during AMHTS. The results of an AMHTS should be evaluated from the viewpoint of health-risk appraisal, because the system is expected to supply useful information regarding one's lifestyle. Our system consists of two health-risk appraisal subsystems. One subsystem estimates the degree of improvement in medical indicators after a patient's lifestyle has been modified. The other subsystem predicts the occurrence of abnormal findings in medical indicators. These health-risk appraisal subsystems provide patients with information about their health-risks, based on their AMHTS results. Our health-risk appraisal subsystems should play an important role in future health education through the application of ordinary AMHTS. PMID- 8341165 TI - Computers, personal health management and aging tomorrow. PMID- 8341166 TI - Cholera--still a major health problem. PMID- 8341167 TI - Blood cholesterol screening: influence of fasting state, biological variation and the single cholesterol assay on total cholesterol level. AB - Postprandial changes in plasma total cholesterol (TC) are minimal and there is essentially no difference between fasting vs random TC concentrations, as reflected in the small diurnal coefficient of variation (CV) for TC of 2.5%. Similarly, a cholesterol-rich meal within the last 24 hours lacked an impact on plasma TC. Thus, random specimens are acceptable in blood cholesterol screening. The intraindividual biological CV (CVb) for plasma TC as measured over a long period was estimated from the data of several published studies to be 6.0%, which, when combined with a probable analytical CV (CVa) of 5% during screening, gave a total intraindividual CV (CVt) of about 8% for the single cholesterol assay. There is consensus that 'high TC values' acquired during screening should be confirmed under the conventional laboratory setting capable of CVa of 3% or less. PMID- 8341168 TI - Acute appendicitis--the University Hospital experience. AB - A 1 year review of 529 cases of acute appendicitis, treated at the University Hospital in 1990, was performed. Perforation rate was 23.7% and delay in diagnosis was found to be significant. Patients above 50 years of age were particularly at risk. Diagnostic error was 19.3% and it was a problem not only in young women but also in children. Temperature and rectal examinations were not found to be helpful in the diagnosis in contrast to leukocytosis. Waiting time for operation was long (median 7 hours), be it for a perforated or a nonperforated appendicitis. PMID- 8341169 TI - A review of acute appendicitis seen in the Taiping District Hospital from July to December, 1990. AB - In a retrospective study, 455 people were found to have been admitted to the Surgical Unit of the Taiping District Hospital, suspected of acute appendicitis in the study period from 1 July to 31 December 1990. However, only 147 (32.3%) were clinically confirmed to have appendicitis and underwent appendicectomy. Out of these, 120 (81.6%) cases were subjected to detailed analysis. The study showed that the commonest age group affected was the 10 to 20 year old. Males were slightly more often affected but there seemed to be an equal distribution among the major races. The diagnostic accuracy, that is the operated cases that were actually acute appendicitis, was 92.5%. The perforation rate was 31.5%. Fifty five percent of patients developed some post-operative complications, of which the commonest was fever. PMID- 8341170 TI - Gas-containing liver abscesses: assessment by ultrasound (US) and computed tomography (CT). AB - Single gas-containing pyogenic liver abscesses in 11 patients were studied by ultrasound and computed tomography (CT). On ultrasound, all abscesses were predominantly echogenic compared to the normal liver parenchyma. The gas collections appeared as hyperreflective areas arranged in clusters associated with acoustic shadowing and ring-down artifacts. Ten abscesses (90%) had ill defined margins on ultrasound, causing underestimation of their sizes in these patients. All abscesses were shown to be multiloculated and had clearly defined borders on CT, not appreciated or mistaken for multiplicity of abscesses on ultrasound. Ultrasound may be inadequate in the evaluation of gas-containing liver abscesses, as they have complex echotexture in addition to ring-down artifacts, acoustic shadows and poorly-defined margins; leading to underestimation of abscess size, difficulty in identifying loculations and erroneous interpretation of multiplicity of abscess cavities. PMID- 8341171 TI - Detection of gene deletions by PCR analysis in a Malaysian patient with Duchenne muscular dystrophy. AB - Duchenne muscular dystrophy (DMD), the commonest X-linked disorder, is a progressive, eventually fatal disease. With the advent of molecular genetics, the Duchenne gene and its protein product, dystrophin, have been characterised. Molecular diagnosis of DMD, identification of carriers and antenatal diagnosis are now possible. We describe here the use, in a Malaysian boy with DMD, of a recent innovation, multiplex polymerase chain reaction (PCR), to obtain molecular diagnosis by detection of dystrophin gene deletions. PMID- 8341172 TI - Profile of extracranial cerebrovascular disease in Kelantan: a study by continuous wave Doppler ultrasonography. AB - The present study outlines the clinical profile and patterns of extracranial vascular abnormalities detected by continuous wave doppler ultrasonography (CWDU) in 100 patients with cerebrovascular insufficiency states. Males outnumbered females (65:35); completed stroke (CS) was a more common mode of presentation than transient ischaemic attacks (TIA); carotid strokes were more common than vertebro-basilar ones; and hypertension was the most common predisposing factor. The CWDU evaluation revealed extracranial vascular disease in 73% of patients. Vascular occlusions were more common in patients with TIA. Overall, 33% of the patients had evidence of proximal obstruction of the cerebral vessels below the neck. The clinical prediction of vascular territory (carotid or vertebro-basilar) matched with the findings on CWDU, but evidence of subclinical multiple-vessel involvement could be detected in 48% of the patients. PMID- 8341173 TI - Response of ovary in young women experiencing laparoscopy under general anaesthesia. AB - This study investigated whether changes in circulating levels of immunoreactive oestradiol-17 beta (E2), progesterone (P) and testosterone (T) occur in women at follicular (n = 18, age 25 to 39 years) and luteal (n = 17, 25 to 39 years) phases of the normal menstrual cycles, experiencing laparoscopy after intravenous sedation with general anaesthesia. The pre- and intra-operative follicular phase plasma steroid hormone concentrations were 153.5 +/- 84.3 vs 297.4 +/- 220.8 pg/ml for E2, 2.0 +/- 3.2 vs 3.3 +/- 3.8 ng/ml for P and 746.6 +/- 415.9 vs 1325.8 +/- 535.1 pg/ml for T, respectively. The corresponding luteal phase steroid levels were 259.7 +/- 120.2 vs 382.7 +/- 188.7 pg/ml, 7.0 +/- 4.8 vs 9.9 +/- 6.1 ng/ml and 819.4 +/- 355.7 vs 1703.5 +/- 1058.1 pg/ml. Using the Wilcoxon rank sum test, intra-operative hormone levels with the exception of P in the luteal phase were found to be significantly elevated (p < 0.05). The results suggest that laparoscopy under general anaesthesia evokes increased secretion of ovarian hormones, possibly via the activation of hypothalamo-pituitary-ovarian axis. PMID- 8341174 TI - The prevalence of endemic goitre in Kelantan, Malaysia. AB - A large-scale study was undertaken in the state of Kelantan, to determine the prevalence of goitre. A total of 2,450 subjects above the age of 15 years were selected from 31 localities in the state and examination for goitre was done using the technique of Perez. The state was divided into 3 areas--coastal area (area 1), inland area (area 2) and the area in between the coast and the inland area (area 3). The overall prevalence of goitre was 36.8% and the prevalence in areas 1, 2 and 3 were 23.0%, 35.9% and 44.9% respectively and ranged from 6.9% in a locality in area 1 to 59.7% in a locality in area 3. In all areas, the prevalence was higher in females than in males. The prevalence of grades I, II and III goitres were 21.5%, 1.0% and 0.5% respectively in area 1, 33.6%, 1.5% and 0.7% respectively in area 2 and 41.7%, 2.2% and 1.0% respectively in area 3. Amongst age groups, goitre prevalence was highest in the 36 to 45 years age group in area 1 (33.9%), in the 15 to 25 years age group in area 2 (39.6%) and in the 26 to 35 years age group in area 3 (54.3%). In all the areas, goitre prevalence was lowest in the above 56 years age group. We concluded that the prevalence of goitre was high in Kelantan and there were regional differences in the prevalence rate within the state. PMID- 8341175 TI - Comparison of the efficacy of single and multiple regimens of carbimazole in the treatment of thyrotoxicosis. AB - Carbimazole, in 3 divided daily doses, is commonly prescribed for the treatment of thyrotoxicosis. However, based on its long intra-thyroid half-life, the drug may be effective when used as a single or twice daily dose. This study was undertaken to determine the effect of once, twice or thrice daily doses of carbimazole on thyroid function in patients with thyrotoxicosis. Seventy previously untreated thyrotoxic patients were randomly allocated to receive carbimazole 30 mg once (group 1), 15 mg twice (group 2) and 10 mg thrice (group 3) daily. All patients were also prescribed propranolol 20 mg thrice daily for the first 4 weeks. Blood was taken for total T3, T4, TSH, blood counts and liver enzymes determinations at the beginning and at 6 weeks of treatment. Only 48 (68.6%) patients were included in the analysis, as the rest defaulted follow-up (20.0%) or blood samples were not available at review (11.4%). Of the 48 patients, 17 were in group 1, 16 in group 2 and 15 in group 3. Following 6 weeks of treatment, there was no significant difference in the mean serum levels of total T3 and T4 between the 3 groups. However, there was a significant decrease in the mean serum levels of total T3 and T4 as compared to the start of the treatment. Four patients (23.5%) in group 1, 4 patients (25%) in group 2 and 3 patients (20%) in group 3 were still thyrotoxic at 6 weeks of treatment, whilst 10 patients (58.8%) in group 1, 6 patients (37.5%) in group 2 and 3 (20%) in group 3 were biochemically hypothyroid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341176 TI - [Anthropometric measurements in Malay children from upper class families in Kuala Lumpur]. AB - This study was done to determine the anthropometric measurement patterns of Malay children from wealthy families in Malaysia and to make a comparison with NCHS reference population. A population of 900 children aged between 3-12 years old from Taman Tun Dr Ismail, Kuala Lumpur (TDI), were examined but only 871 of them were eligible for the study. Weight, height, mid-arm circumference and skin fold thickness were measured. The increment pattern of anthropometric measurements of TDI children was quite similar to NCHS except for having a lower median weight for age and height for age. There was prepubescent increase in skin folds thickness in both sexes, followed by a midpubescent decrease and a late pubescent increase. The study indicated that Malay children from a wealthy background have growth rates comparable to children in the West, hence NCHS percentile charts are suitable as a reference for comparing the nutritional status of Malay children in Malaysia. PMID- 8341177 TI - Painful thyroiditis in postpartum period. AB - Destructive thyroiditis commonly occurs during the postpartum period, with a prevalence rate of 5% to 16%, and is mainly due to postpartum autoimmune thyroiditis (PPT) and, very rarely, to subacute thyroiditis. The thyroiditis is similar to Hashimoto's thyroiditis and is generally painless in nature, although cases with painful thyroiditis have been described. We report a case of painful destructive thyroiditis occurring during the postpartum period, which was clinically and biochemically indistinguishable from the variant of painful PPT or subacute thyroiditis. Fine needle aspiration cytology showed multi-nucleated giant cells diagnostic of subacute thyroiditis. PMID- 8341178 TI - Skin cancer caused by chronic arsenical poisoning--a report of three cases. AB - The association of arsenical poisoning with the development of skin cancer is well-known. In Malaysia, arsenic has been shown to coexist with tin in tin-mining land. Our preliminary investigation has shown that the level of arsenic in well water from a tin-mining area is high. We report 3 patients with cutaneous lesions typical of chronic arsenical poisoning such as hyperpigmentation, keratoses and skin cancer. These patients have positive histories of previous domicility in tin mining areas. We conclude that these patients developed chronic arsenical poisoning from drinking well water polluted with arsenic from the tin-mining soil. PMID- 8341179 TI - Cytokines in infection. AB - Cytokines are central to the development of effective immunity against microbial pathogens and their beneficial effects in the control of a variety of infections of man and animals are well-documented. However, it appears that cytokines may also have detrimental effects in infections by actually enhancing microbial growth. These observations emphasise the fact that many successful pathogens possess mechanisms enabling them to evade the immune response and that caution needs to be exercised in using cytokines as therapeutic agents to control infections in various human diseases. PMID- 8341180 TI - AIDS presenting as unresolved pneumonia in a 9 year old boy. PMID- 8341181 TI - Tetracycline-resistant vibrio cholerae El Tor. PMID- 8341182 TI - Health care research in the developing world: a successful educational experiment. PMID- 8341183 TI - Primary aldosteronism: a new understanding. PMID- 8341184 TI - Class III antiarrhythmic action: the way forward? PMID- 8341185 TI - Extrapulmonary tuberculosis in children. AB - OBJECTIVE: To investigate an apparent increase in the number of children admitted to the Royal Alexandra Hospital for Children with extrapulmonary tuberculosis (TB). Further, to highlight both the seriousness of this disease and the difficulty of its diagnosis, and to draw attention to factors such as ethnic origin in identifying children at risk. DESIGN: Clinical and microbiological data were collected for all children admitted to the hospital with a confirmed diagnosis of TB. A standardised incidence ratio (SIR) was used to analyse the number of children admitted with extrapulmonary TB in 1990-1991 compared with 1982-1989, and in 1987-1991 compared with 1982-1986. RESULTS: Eleven children (five of these in 1990 and 1991) had extrapulmonary TB (4, central nervous system; 3, osteomyelitis; 2, cervical lymphadenitis; 2, abdominal). One was Aboriginal and 10 were from families of overseas origin. Twenty-one others had pulmonary TB and 17 of these were from families of overseas origin. The apparent increase in the number of admissions for extrapulmonary TB was not statistically significant. CONCLUSION: There has been a recent increase in the number of children hospitalised with extrapulmonary TB but when this is compared with the increase in children hospitalised for all causes, the increase is not significant. Immigration and the continuing contact of children with infected adults appear to account for most cases of TB in this series. PMID- 8341186 TI - Evaluation of a community-based asthma management program in a population sample of schoolchildren. AB - OBJECTIVE: To assess the effect of a community-based management program, incorporating both education and treatment directed at children, parents, doctors, pharmacists, community nurses and school teachers. DESIGN: The effect of this intervention in a population sample of 65 children with a wide range of morbidity due to asthma was compared with a control group of 55 children living in a different area. Both groups were re-evaluated concurrently after three and six months. MAIN OUTCOME MEASURES: Forced expiratory volume in one second (FEV1); bronchial responsiveness to histamine measured as the provoking dose causing a 20% fall in FEV1 (PD20FEV1) and as dose-response ratio (DRR); Airflometer variability; symptom frequency; and knowledge of asthma. Morbidity was measured by parents using a self-administered questionnaire and included days absent from school and unscheduled doctor or emergency room visits. RESULTS: At three months, the intervention group had a significant improvement in knowledge of asthma compared with both their baseline and the control group's change in knowledge. Also, FEV1 improved in this group and symptoms which limit activity decreased significantly. However, the largest improvements were recorded at the six-month follow up. In the intervention group, bronchial responsiveness and night cough were reduced significantly and FEV1 was improved, compared with both baseline measurements and the control group. Knowledge of asthma also improved significantly from baseline, and unscheduled doctor or emergency room visits were reduced. CONCLUSION: These improvements in this group of children, many of whom had mild asthma, verify that community-based management programs can be effective in treating childhood asthma. PMID- 8341187 TI - On our selection: predictors of medical school success. AB - OBJECTIVE: To review predictors of academic success in one Australian medical students with predictors rated retrospectively. PREDICTORS: Success and involvement in academic and non-academic pursuits over the final two school years and at university, as well as study and external employment variables. RESULTS: Superior performance over the medical course was predicted by younger age and by being involved in debating in the final school year, immediate entry to the course, having English as a first language, completing school in Australia, having a higher Higher School Certificate (or equivalent) English score, as well as leadership responsibilities in the last year at school, with the first two variables remaining significant in a multiple regression analysis. English and communication skills were two of the five predictors of success for students who did not have English as their first language. For students who had English as their first language, the important predictors were younger age and having debated in the final high school year. CONCLUSIONS: These results, considered with some other recent reports, suggest that academic success in a medical course is predicted to a surprisingly high level by competence in English. Both the importance of communication skills to the practice of medicine, and their assessment in those seeking entry to medical schools, are considered. PMID- 8341188 TI - A comparison of a bodyweight dose versus a fixed dose of nebulised salbutamol in acute asthma in children. AB - OBJECTIVE: To compare the efficacy of salbutamol as a fixed dose Ventolin Nebule (2.5 mg) and as variable dose respirator solution (0.1 mg/kg bodyweight). DESIGN: Multicentre, randomised, double-blind, parallel group comparison. SETTING: The Emergency Departments of the Royal Children's Hospital, Melbourne, Victoria; Princess Margaret Hospital for Children, Perth, Western Australia; and The Children's Hospital, Sydney, New South Wales. PATIENTS: Ninety-nine children between four and 12 years of age who presented to the Emergency Departments with mild to moderate acute asthma from May to December 1990. INTERVENTIONS: Children enrolled in the study were randomly allocated to one of two groups. Group 1 received one Nebule (2.5 mg salbutamol in 2.5 mL aqueous solution) delivered by wet nebulisation. Group 2 received salbutamol (approximately 0.1 mg/kg bodyweight) diluted with saline to 2.5 mL, delivered by identical wet nebulisation. MAIN OUTCOME MEASURES: (i) Clinical score; (ii) pulse oximetry; and (iii) peak expiratory flow rate (PEFR) where possible--measured before, and at 15 and 30 minutes after treatment with salbutamol. RESULTS: The clinical score significantly improved in both treatment groups after 15 minutes (P < 0.001), but the difference between the two treatments (adjusted for covariates) was not significant (P = 0.97). Both preparations of salbutamol produced a significant increase in oxygen saturation after 15 minutes (P < 0.05), while the difference between the two treatments (adjusted means) was not significant (P = 0.46). Peak flow measurements were available for 65 of the 99 patients. Both preparations of salbutamol produced highly significant (P < 0.001) improvements in PEFR at 15 minutes after treatment. The difference in peak flow rates between the two treatment groups (adjusted means) was not significant (P = 0.89). The study had a power of 0.8 to detect differences between treatments of 9% PEFR (percentage predicted), 0.8% oxygen saturation and 0.77 units of clinical score. CONCLUSIONS: A fixed dose of nebulised salbutamol is as efficacious as a salbutamol dose calculated for bodyweight in children with mild to moderate acute asthma. PMID- 8341189 TI - Viral zoonoses. AB - Viral zoonoses cause overt disease in humans and other animals or silent infections in animals and overt disease in unnatural hosts such as humans. Often the virus and its animal host have evolved together and learned to live together. Infection may spread freely between the natural host animals and cause no signs of disease, but this balance may be upset by many factors, including stress, changing environmental conditions and mutations in both viruses and hosts. Infection of an unnatural host may cause clinical disease but no further spread of the virus. Examples of viral zoonoses both old and new are used to illustrate some of these points, and two will be described in detail--Rift Valley fever and influenza. PMID- 8341190 TI - Treatment of asthma in children and adolescents: the need for a different approach. AB - OBJECTIVE: To provide a concise, balanced summary of the principles of management of asthma in children and adolescents. DATA SOURCES: Current medical literature and the clinical experience considered during the deliberations of the Australian Paediatric Asthma Special Interest Group. KEY ISSUES: There is evidence of both under-treatment and over-treatment of childhood asthma in Australia. The spectrum of asthma severity is very broad, most children with asthma having mild infrequent episodes that do not require regular preventive therapy. The guidelines presented here provide a framework for accurately assessing the pattern and severity of asthma, identifying those children who require preventive therapy and making a rational decision about the appropriate preventive agent and delivery device. CONCLUSIONS: When prescribing preventive therapy, a careful assessment of the relative risks and benefits should be made in the light of the underlying asthma severity. The level of therapy should be reconsidered regularly to ensure control is maintained with minimum dosages, particularly for inhaled corticosteroids. Recommendations are provided to ensure a normal quality of life for children with asthma, with guidelines to minimise adverse effects of therapy. PMID- 8341191 TI - Asthma management in general practice. AB - OBJECTIVE: To provide guidelines for management of asthma in general practice. DATA SOURCES: Selected articles, particularly those relating to general practice. CONCLUSION: Better management of asthma requires strategies for dealing with long term management as well as acute attacks. Planning such strategies and implementing personal management plans for each patient requires assessment of asthma severity; determination and maintenance of best achievable lung function, with avoidance of trigger factors, regular monitoring, and appropriate drug therapy; a written self-management plan as a basis for patient and family education; and regular review. PMID- 8341192 TI - Thyroid disease. AB - Hyperthyroidism and hypothyroidism are common disorders in the elderly and may remain unrecognised until a patient presents with an apparently unrelated problem. The finding of an elevated level of thyroid stimulating hormone (TSH) with a normal serum thyroxine (T4) level represents "subclinical hypothyroidism", which does not necessarily require treatment. Iodine can precipitate hyperthyroidism in patients with autonomous thyroid tissue and the iodine-rich antiarrhythmic agent, amiodarone, may cause either hyperthyroidism or hypothyroidism. The metabolism and clearance of numerous therapeutic agents is altered when thyroid status is abnormal, so that dose adjustment may be necessary. In cardiac failure secondary to hyperthyroidism, great care must be taken in prescribing beta-blockers and diuretics; dosage of digitalis preparations may need to be increased. Thyroid replacement therapy can aggravate myocardial ischaemia and it may be appropriate to consider coronary artery bypass grafting before hypothyroidism is fully corrected. Antithyroid drugs, surgery and radioactive iodine all have a place in the treatment of hyperthyroidism in the elderly, depending on factors such as disease severity and the characteristics of the goitre. T4 may be given together with an antithyroid drug in a "block replace" regimen. PMID- 8341193 TI - A prospective audit of asthma management following emergency asthma treatment at a teaching hospital. AB - OBJECTIVE: To audit the assessment and treatment of acute asthma and the subsequent application of the Australian Asthma Management Plan. DESIGN: Prospective audit of case notes with follow-up telephone questionnaire and clinical assessment at 8-12 weeks after discharge. SETTING: Tertiary-level teaching hospital. MAIN OUTCOME MEASURES: Comparison with published guidelines for acute and ongoing asthma management. RESULTS: Asthma severity was objectively assessed in the Primary and Emergency Care Department, with lung function performed in 95% of acute presentations. Clinical history and examination were documented completely in 28% of presentations. Corticosteroids were underused and there was inappropriate use of ipratropium bromide. At 8-12 weeks follow-up most patients were symptomatic with limited activity due to asthma (46%) and impaired lung function (66%). One-third of patients were undertreated. Asthma management skills were seriously inadequate: only 20% of patients were performing peak flow monitoring, and only 21% recalled receiving specific instructions for the management of future exacerbations. Inhaler technique was inadequate in one-third of patients and asthma knowledge was poor. These deficits were more frequent in patients not admitted to hospital. CONCLUSION: This audit identified suboptimal assessment and treatment of acute asthma, and deficits in the implementation of the Australian Asthma Management Plan following discharge. Patients in this audit were undertreated and not provided with the skills to manage future attacks of asthma. PMID- 8341194 TI - New developments in anti-asthma drugs. AB - OBJECTIVE: To review the current approach to the management of bronchial asthma with particular reference to drug therapy. DATA SOURCES: All significant English language journals were searched for current studies, particularly controlled clinical trials, in the management of asthma. STUDY SELECTION: Sixty articles were reviewed. They were selected on the basis of the known reputation of the author or the unit from which the study emanated, the place that the study has assumed in academic respiratory circles, and whether the study contributed something new to our understanding of drug therapy in asthma. Review articles from eminent scientific bodies were also analysed. CONCLUSIONS: Asthma is an inflammatory disease and therapy must be directed towards this as well as to bronchoconstriction. Inhaled corticosteroids are the mainstay of treatment and inhaled beta-agonists are best used on an as needed basis. Regular objective assessments of patients' progress are essential, as are written, individualised action plans. The adjunctive use of other drugs is discussed and new therapies which may prove useful in the future are reviewed. PMID- 8341195 TI - Genetic susceptibility to common diseases. PMID- 8341197 TI - Planning bedside teaching--7. Explication of the clinical experience. PMID- 8341196 TI - Hypothermia, hyperhidrosis, myokymia and increased urinary excretion of catecholamines associated with a thymoma. AB - OBJECTIVE: To report a rare syndrome associated with a thymoma and its first successful treatment with gammaglobulin. CLINICAL FEATURES: A 49-year-old white male presented with marked hypothermia, hyperhidrosis, myokymia and increased urinary excretion of catecholamines four weeks after complete excision of a malignant thymoma. He became increasingly drowsy, obtunded and required ventilatory support. INTERVENTION AND OUTCOME: A catecholamine secreting tumour was excluded and he was treated with intravenous gammaglobulin for five days, with dramatic improvement in his condition. Six months later he remains in remission. CONCLUSION: The response to treatment in this patient suggests an immunological pathogenesis for this rare group of symptoms associated with a thymoma. PMID- 8341198 TI - Mohs surgery explained. PMID- 8341199 TI - Mohs surgery explained. PMID- 8341200 TI - The acceptability of personal invitations to a mammographic screening program. PMID- 8341201 TI - Illness associated with blue-green algae. PMID- 8341203 TI - Anabolic steroid use and cerebellar haemorrhage. PMID- 8341202 TI - Rheumatic fever and chronic rheumatic heart disease in Yarrabah aboriginal community, north Queensland. PMID- 8341204 TI - Non-pharmacological treatment of cramps. PMID- 8341205 TI - Homelessness and mental illness in rural New South Wales. PMID- 8341206 TI - Perspectives on tropical health. PMID- 8341207 TI - Topical terbinafine for tinea infections. PMID- 8341208 TI - Malnutrition of children in developing countries: what can we do? AB - This informal paper is a personal account of the development of my work on malnourished children, starting with clinical studies in Jamaica and the challenge of an unacceptably high mortality rate; moving on to the problem of how to define less severe malnutrition in the community; and ending with some reflections on the enormously difficult question of prevention and the contribution that richer countries such as the UK could make. PMID- 8341209 TI - A time of hate and suffering. PMID- 8341210 TI - Eighth international conference on radiation and health. PMID- 8341211 TI - Violence: a public health concern. PMID- 8341212 TI - When is the optimum time to harvest peripheral blood stem cells in children following standard dose chemotherapy? AB - The optimal time for peripheral stem cell harvest may be predicted by recovery of blood count following priming doses of chemotherapy. Bone marrow growth factors have also been used to enhance yield. Both these manoeuvres may necessitate alterations to standard treatment programmes. In order to determine whether adequate peripheral stem cell yields could be obtained without altering chemotherapy regimens, 18 children with either leukaemia or solid tumours were studied. Circulating bone marrow progenitor cells were estimated by CFU-GM cultures in soft agar. There were 8 males and 10 females, median age 5.6 years (range 2-13 years). Six out of 13 studies in leukaemia patients were done when the bone marrow contained significant leukaemic blasts, and in 2 of 9 studies in patients with solid tumours, there was active infiltration of the bone marrow. In 15 of 23 studies, a rise in CFU-GM levels to greater than 1,000 x 10(3)/l were observed following postchemotherapy aplasia. Maximum CFU-GM levels were maintained for only 1-2 days and could be predicted by the achievement of a total white cell count in the region of 2 x 10(9)/l and platelet count around 100 x 10(9)/l. Neutrophil recovery did not predict the rise in CFU-GM levels. A rapid rise in monocyte levels also preceded maximum CFU-GM levels. Predictably, the CFU GM counts were lower in patients who were heavily pretreated, but in several children, the counts were sufficient to predict an adequate harvest to be used in conjunction with bone marrow autotransplantation. It is concluded that in children with active bone marrow recovery, chemotherapy priming or the use of bone marrow growth factors may not be necessary to achieve useful stem cell harvests. PMID- 8341213 TI - Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia. AB - Three hundred twenty-six children with bone marrow (BM) relapse of non-B acute lymphoblastic leukemia (ALL) were stratified according to the time of relapse in three consecutive multicenter trials--ALL-REZ BFM 83, 85, and 87. Employing an intensive polychemotherapy regimen, extramedullary involvement appeared to be predictive of superior outcome in both strata as well as in the whole group (probability of 7-year event-free survival (EFS) 42% in combined vs. 15% in isolated BM relapse, P = 0.015). Children with combined BM relapse occurring later than 6 months after completion of front-line therapy reached EFS estimates of 60%. We conclude that results of conventional polychemotherapy with BFM relapse protocols are equivalent to those achieved by bone marrow transplantation in children with late combined BM relapse. PMID- 8341214 TI - Increased risk of cardiac dysfunction after anthracyclines in girls. PMID- 8341215 TI - Carcinoma of the choroid plexus: a pediatric experience. AB - Carcinoma of the choroid plexus (CCP) is a rare tumor of the central nervous system which occurs more frequently in patients under 3 years of age. We report 10 cases of CCP in children. There were 5 males and 5 females, aged 5 to 84 months at diagnosis (median 32 months). Eight CCP were located in the lateral ventricle and 2 in the fourth ventricle. All patients underwent initial surgery, with complete resection in 5 cases. Postoperative treatment included radiotherapy alone in 4 patients, chemotherapy alone in 4, both in 1 patient, and no further treatment in one patient. Six patients remain in first continuous complete remission with a follow-up of 12 to 156 months (mean 34 months). Five of these six patients had a complete surgical resection of their tumor and 4 of them received chemotherapy alone. A comparison with the series in the literature suggests that total resection of the tumors is the major prognostic factor for survival. Recourse to additional treatments to prevent local relapses and CNS dissemination seems necessary. In our opinion, radiotherapy should be avoided as far as possible because of its deleterious effect in very young children. As some of the long term survivors did not receive radiation treatment, we conclude that CCP can be treated post operatively using chemotherapy protocols designed for infants with malignant brain tumors. PMID- 8341216 TI - Chemotherapy in the management of infantile fibrosarcoma. AB - Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating. PMID- 8341217 TI - Low dose continuous infusion doxorubicin in children and young adults. AB - Ten patients (age range 3.2-26.3 yrs) with relapsed or resistant malignancies received a total of 20 courses of low dose continuous infusion doxorubicin (3 mg/m2/day for 28 days) delivered by portable Graseby infusion pumps via central venous catheters. Each patient received a median dose of 144 mg/m2 (range 87 261). Four patients responded to treatment (1 complete response (CR) and 3 partial response (PR)) and performance status improved in seven patients. Overall toxicity was minimal: WHO Grade 4 anaemia in 2/18 courses, Grade 4 neutropenia in 1/18, Grade 3-4 thrombocytopenia in 3/18, nausea and vomiting of Grades 2 and 4 in 4/20 and 1/20 respectively, and mucositis of Grades 2 and 4 in 2/20 courses each. Cardiac toxicity was assessed using echocardiography, and fractional shortening remained within normal limits in all patients. Low dose continuous infusion doxorubicin is a feasible, well tolerated, ambulatory therapy in children and may be an effective way of delivering doxorubicin with less toxicity, thus enabling the development of more dose intensive regimens. PMID- 8341218 TI - N-myc oncogene and urinary catecholamines in children with neuroblastoma. AB - This paper reports the analysis of N-myc amplification, urinary vanillylmandelic acid (VMA), and norepinephrine (NE) excretion and survival in 22 children with neuroblastoma and 7 with ganglio-neuroblastoma. Five patients had N-myc amplification (from 30 to more than 200 copies), all of whom had advanced-stage disease. The urinary excretion of VMA was normal in all of them, only one showed increased NE excretion. All patients with stage C-D disease and one copy of N-myc had increased VMA urinary excretion and increased (9/14) or normal (5/14) NE urinary excretion. All patients with stage A or B disease had one copy of N-myc. Half of them showed increased VMA urinary levels, while only 3/10 showed increased NE urinary values. Comparison of cumulative survival curves in relation to N-myc amplification and to VMA and NE urinary excretion showed a clear parallelism. Amplification of N-myc corresponded to normal VMA and NE urinary excretion, and was associated with the worst prognosis (P < 0.01), while increased VMA and/or NE excretion was found in patients with only one copy of N myc. PMID- 8341219 TI - James Ewing (1866-1943): "the chief". AB - "It is a growing conviction that to know cancer in man, one must study the disease most carefully in the human subject. Personally, I do not look for any startling advances or sensational discoveries, since it is much more likely that a steady reduction in the mortality from cancer will come chiefly from a large number of separate factors, of which the most significant appear to be increased control of the conditions leading to cancer, more general recognition of the preliminary stages of the disease, early diagnosis, and treatment of the established disease. From the consideration of these various functions of the modern cancer research hospital, I think that it must be evident that such an institution not only can justify its existence, but fills a very urgent need without which, progress of cancer research would be handicapped, and much relief that might early be extended to cancer victims would be unavailable. Nor is there any doubt that the function of supporting such an institution is properly exercised by the State, which support should be continuous and liberal"--James Ewing [2]. PMID- 8341220 TI - Ganglioglioma. PMID- 8341222 TI - Clear cell sarcoma of the kidney in a 4-month-old infant: a case report. AB - A case of clear cell sarcoma of the kidney is described in a 4-month-old male infant. The tumor had a typical histological pattern, consisting of sheets of tumor cells possessing "empty" nuclei set within a delicate capillary network. There was extensive necrosis and tumor cell cytoplasm contained vimentin. This tumor occurs only rarely in infants less than six months of age. The different renal neoplasms of childhood have diverse prognoses and demand specific therapy so that accurate diagnosis is mandatory. The present case illustrates that clear cell sarcoma, a highly malignant neoplasm, must be considered in the differential diagnosis of a renal mass occurring in this age group. PMID- 8341221 TI - Tumor lysis syndrome after combination chemotherapy for ovarian cancer. AB - Tumor lysis syndrome is infrequently encountered following the treatment of solid tumors. A 47-year-old woman developed this syndrome after receiving combination chemotherapy for ovarian cancer. The levels of serum lactate dehydrogenase, uric acid, phosphate, and creatinine increased, whereas the serum calcium level decreased. These metabolic abnormalities were treated successfully using a combination of vigorous intravenous hydration, parenteral bicarbonate to keep urinary pH > 7, furosemide, and allopurinol. This unusual and easily treatable complication should be anticipated in patients with rapidly growing ovarian cancer undergoing aggressive treatment. PMID- 8341223 TI - [Varicella: how and when to start antiviral treatment]. AB - The Meeting "An Update on Chickenpox" (Florence, 19-3-1993) has contributed to verify, in the light of the most recent acquisitions, the new guidelines for a correct rationale in the diagnosis and therapy of chickenpox. The present availability of an effective specific antiviral therapy for chickenpox (acyclovir) leads to a careful selection of patients to be treated. The high incidence of chickenpox morbidity keeps long unaltered and, beyond the usually benign onset of the primary infection in the child, the severity of this pathology in particular subjects and situations at risk is to be certainly underlined. Treatment is suggested for cases of chickenpox contracted inside the family. Generally, boys are at higher risk. Adolescents and adults, usually with a lower incidence, report a much higher severity of the acute onset and complications. Another category to be certainly treated is the one--in constant increase--of immunocompromised subjects. In any case, acyclovir treatment improves the symptomatologic evolution (pruritus and fever) and duration of clinical course. Among the progenitors of acyclovir, Valacyclovir seems to have the best prospects of success for the immediate future of antiviral therapy. PMID- 8341224 TI - [L-T4 malabsorption determined by intolerance to cow's milk proteins and celiac disease in a patient with congenital hypothyroidism. A clinical case]. AB - An infant with congenital hypothyroidism (CH) is described who in the course of thyroxin replacement therapy developed cow's milk protein intolerance (CMPI) and subsequently coeliac disease (CD). The presence of these two pathologies interfered with the intestinal absorption of L-thyroxin (L-T4) and made the appropriate management of CH difficult. A male patient, formula fed from birth, was screened for CH at 5 days of age. CH was confirmed and L-T4 treatment (6.8 micrograms/kg/day per os) begun at 35 days of age. Seen after 3 weeks because of feeding problems and impaired growth and with a serum T4 concentration of 4.7 micrograms/dl and a TSH of 56 mU/ml, his replacement dose was increased to 12 micrograms/kg/day. One week later, the child was hospitalized because of vomiting, acidosis and shock. CMPI was diagnosed and the child began a diet with a hydrolyzed milk protein food. After 7 weeks the serum T4 improved to 11 micrograms/dl, the TSH decreased to 10 mU/ml, while maintaining the 12 micrograms/kg dose. After 2 months an oral challenge with cow's milk confirmed the diagnosis of CMPI with a concomitant decrease in serum T4 to 6.4 micrograms/dl, while TSH rose to 64 mU/ml. Weight and T4 levels normalised with CMPI diet. At 12 months of age the patient presented anorexia and impaired growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341225 TI - [Chondrodysplasia punctata (the Conradi-Hunermann syndrome). A clinical case report and review of the literature]. AB - A case of chondrodysplasia punctata (CDP) a mild form of Conradi-Huenermann type in a male newborn is presented. CDP is a bone dysplasia with the hallmark of stippling of the epiphyses. Although stippling of the epiphyses can be seen in several disorders and syndromes such as Zellweger sy., trisomy 21 sy., trisomy 18 sy., fetal alcohol syndrome, following ingestion of warfarin or phenytoin during pregnancy, the term describes a group of different clinical features involving the bones, skin and eyes with different inheritance transmission: autosomal dominant type, autosomal recessive type, X-linked dominant type, X-linked recessive type with deletion of terminal short arm, duplication of short arm of chromosome 16. The rhizomelic form of CDP is considered a peroxisomal disorder, due to reduced activity of some enzymes: DHAP-AT, phytanic acid oxidase, alkil DHAP synthase. The Conradi-Huenermann syndrome has also been considered by some authors as a peroxisomal disorder. A brief description of these disorders and their classification in groups will follow. PMID- 8341226 TI - [The persistence after clinical recovery and the suspension of therapy of altered ESR values in a case of meningococcal sepsis and septic shock]. AB - The paper describes a case of meningococcal sepsis and septic shock treated with Ceftriazone, Dexamethosone, plasma and heparin. It was observed that contrary to other hematological parameters, ESR levels remained high for one month after the suspension of antibiotic therapy and complete clinical recovery. The authors relate this alteration of ESR values to the administration of plasma during the acute phase of the disease. PMID- 8341227 TI - [The efficacy of aztreonam in a "bolus dose" in the therapy of urinary tract infections in neonates]. AB - A "bolus dose" of aztreonam was used to treat a sample group of 46 neonates suffering from urinary tract infections caused by bacteria thought to be sensitive to aztreonam. This treatment proved efficacious in approximately 80% of cases. PMID- 8341228 TI - [To pediatricians who care for infants with Wolman's disease. Advice for an efficacious treatment]. PMID- 8341229 TI - [The international nomenclature of so-called "constitutional bone diseases"]. PMID- 8341230 TI - [The growth of the low-birth-weight neonate: assessment at 3 years]. AB - Follow-up studies of low-birth-weight (LBW) neonates have shown a high incidence of growth failure in the first years of life. We evaluated the growth attainment (weight, length and head circumference) in 182 LBW neonates discharged from our Intensive Care Unit between 1982-84 and included in a 3 years follow-up program. The aim of the study is to analyze the correlation between gestational age (GA) and subsequent growth failure. Neonates included in the study were divided in 4 groups (G) according to GA: I G < or = 30 weeks GA; II G = 31-33 weeks GA; III G = 34-36 weeks GA; IV G > or = 37 weeks of gestational age. Growth was evaluated at 40 weeks GA on the basis of Lubchenco and Battaglia centiles, and thereafter at 12, 24 and 36 months according to Scalamandre greeds. Subnormal weight (< 10 degrees centile) was still evident at 3 years of age in 16.7% of the most premature babies (group I), in 6.2% of babies born between 31 and 33 weeks GA (group II), in 7.1% of babies in group III and in 16.6% of LBW babies born at term of gestation (group IV). Length measurements were satisfactory in PT babies as none of them showed a length < 10 degrees centile by 24 months of age. On the contrary, in the term LBW neonates group 15.6% of babies still showed subnormal length at 3 years of age. Head circumference remained < 10 degrees centile in 16.6% in the I group, in 6.2% in the II group, 21% in the III group and 30% in the IV group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341231 TI - [The clinical evaluation and immunological response of a new measles vaccine]. AB - For a number of years the measles vaccine has been tabled to be included among the compulsory vaccines with the not impossible aim of wiping out this disease. In practice, however, there have been isolated attempts to impose mass vaccination but, given that it is not compulsory, there has been a certain degree of resistance to the vaccine. In an attempt to interpret the reasons for this resistance we have identified three main causes: cultural heritage by family doctors and sometimes pediatricians ("a disease which is important to have had"). Limited information with underestimation of damaging effects of disease overemphasis of side-effects of vaccine and, among these, in particular fever which 30-35% of vaccinated children present between day 8-10, and the possible allergic reaction (chicken embryos-antibiotics). Using the latter as a starting point, we assessed the efficacy and tolerability of the Moraten Berna vaccine on 165 children aged between 10 months and 8 years. This vaccine is prepared using the Edmonston Zagreb strain cultured in diploid human cells, and does not therefore contain heterologous proteins, seroconversion was assessed in 54 of the vaccinated children (aged 10 months--3 years) by blood sample collected following an interval of between 40 and 120 days after vaccination. Anti-measles antibody titering was assayed using a neutralisation test on plates of cellular monostrate by assessing the titer (starting dilution of serum in test: 1:8). Seroconversion, as shown in table I, was obtained for all vaccinated subjects who presented a mean antibody titer of 916 mUI/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341232 TI - [Cranial fractures during growth. An analysis of the authors' personal cases and therapeutic management of such childhood pathology]. AB - Growing skull fractures are a rare complication of head injury with a dome fracture. The cases described in literature highlight a higher frequency of this pathology in children under than over three years of age. The authors describe 4 personal cases, underlying the clinical, diagnostic and therapeutic aspects. The aetiological hypothesis of a dural tear and its anatomic-pathological evolution are investigated. The surgical technique of dural and bony repair is also discussed. The authors conclude that this complication must be recognized early in order to obtain very good results after surgical therapy. PMID- 8341233 TI - [The predictive value of antigliadin antibodies (AGA) in the diagnosis of non celiac gastrointestinal disease in children]. AB - Recent antigliadin antibody (AGA) determination has become an important diagnostic tool in coeliac disease (CD). Although this test has high sensibility for the disease, it is less specific, especially for IgG class, because of its having been found in some acute and chronic common intestinal childhood diseases. We studied the behaviour of AGA, IgA and IgG, in 234 children affected by various gastrointestinal diseases, comparing the results with those obtained in 125 coeliac children and 788 normal children. The intestinal diseases were as follows: irritable bowel syndrome, cow's milk protein intolerance, acute infectious diarrhoea, parasitosis, lactase deficiency, recurrent abdominal pain, cystic fibrosis, chronic constipation, gastroesophageal reflux, intestinal lymphangiectasia, chronic intractable diarrhoea and nodular lymphoid hyperplasia. Our results showed that while AGA-IgA were absent in all children studied, with the exception of 3 cases of acute diarrhoea, a moderate percentage of AGA-IgG was observed in subjects with cow's milk protein intolerance, acute diarrhoea, irritable bowel syndrome, lactase deficiency, chronic intractable diarrhoea and in a low percentage of children with parasitosis, intestinal lymphangiectasia and nodular lymphoid hyperplasia. There was no antibody movement in subjects with cystic fibrosis, gastroesophageal reflux, recurrent abdominal pains and chronic constipation. The different behaviour of the two antibody classes could be explained by the fact that AGA-IgG were detected in diseases where scattered areas of mucosal damage could allow the permeability of the macromolecules inducing passage of gliadin through the mucosal barrier and immune system-induced antibody stimulation. PMID- 8341234 TI - [A critical review of the problem of children at audiological and phoniatric risk in the first year of life]. AB - The "M. L. Marenzi" Centre of Infantile Otophoniatrics, in collaboration with the Department of Neonatal Pathology of the Fatebenefratelli Hospital in Milan, performed longitudinal controls of an audiological and phoniatric type in 252 children. In the present study attention is focused in particular on audiological evaluations made in a group of 71 infants aged from 6-9 months old. During audiological tests the evaluation of auditory capacity and the type of response to acoustic stimulus were taken into account. The behavioural observation of selective attention to sound is a very important index of the maturity of sensorial patterns. The retarded development of response to an acoustic stimulus may indicate future communication disorders. The type of response to acoustic stimulus obtained in 71 infants were compared with those in a further two groups of children: the first comprised 3822 children with no audiological risk, and the second 3755 children at audiological risk according to Feinmeser and Telly's expanded list. This comparison highlighted a significant persistence of an archaic-type response in the group of infants from the Department of Neonatal Pathology. It is therefore essential that these children are examined further from a phoniatric point of view. PMID- 8341235 TI - Emergency department response to domestic violence--California, 1992. AB - A 1993 national poll found that 34% of adults in the United States report having witnessed a man beating his wife or girlfriend and that 14% of women report that a husband or boyfriend has been violent with them (1). Studies suggest that as many as 30% of women treated in emergency departments (EDs) have injuries or symptoms related to physical abuse (2). A national health objective for the year 2000 is for at least 90% of hospital EDs to have protocols for routinely identifying, treating, and referring victims of sexual assault and spouse abuse (objective 7.12) (3). The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has also recommended that accredited EDs have policies, procedures, and education in place to guide staff in the treatment of battered adults (4). To assess progress toward the national health objective for the year 2000 and the JCAHO standards, all active EDs in California were surveyed during November-December 1992 about their policies and practices for the treatment of battered adults. This report presents findings of this survey. PMID- 8341236 TI - Radical prostatectomies--Wisconsin, 1982-1992. AB - Prostate cancer incidence and death rates have increased during the past decade in the United States (1). In addition, a recent study of the Medicare population indicated that the rate of radical prostatectomies (the removal of the prostate gland, ejaculatory ducts, and seminal vesicles) increased nearly sixfold from 1984 through 1990 (2). To examine trends in prostate cancer incidence and surgical treatment in Wisconsin, the Wisconsin Division of Health assessed data from 1982 through 1992. This report summarizes the results of this study. PMID- 8341237 TI - Tuberculosis--Western Europe, 1974-1991. AB - In several industrialized countries, declines in trends in reported tuberculosis (TB) have stabilized or reversed. This phenomenon was first recognized in the United States and subsequently observed in Western European countries. This report summarizes a 1992 assessment of trends in TB morbidity and mortality in 15 countries of Western Europe (Table 1) by the Tuberculosis Program of the World Health Organization (WHO). PMID- 8341238 TI - [Stimuli from surgical stress and epidural anesthesia]. PMID- 8341239 TI - [Treatment of recurrent laryngeal nerve paralysis by several types of nerve suture]. AB - Although simple neurorrhaphy of the injured recurrent laryngeal nerve usually results in impaired movements of the vocal cord because of misdirected regeneration, phonation recovers because the vocal cord maintains tension during phonation. Simple neurorrhaphy is possible in only a few of patients who have had their nerve severed because of thyroid surgery for thyroid cancer. We tried free nerve grafting, vagus nerve-recurrent nerve suture and ansa cervicalis-recurrent nerve suture as well as the simple neurorrhaphy in 3, 1, 1 and 3 patients, respectively. All of the 8 patients who had repair of the recurrent nerve recovered from hoarseness. Maximum phonation times of these patients ranged from 17 to 41 sec with a mean of 26.5 +/- 9.6 sec, which were significantly longer than those of 23 patients without nerve repair. Each modality of the repair obtained similar good results, although the patient who underwent vagus-recurrent suture required a longer period for recovery. These results indicate that not only simple neurorrhaphy of the recurrent nerve but also free nerve grafting, vagus nerve-recurrent nerve suture, or ansa cervicalis-recurrent suture are effective in recovery of the phonation in patients with peripheral and unilateral recurrent nerve paralysis. PMID- 8341240 TI - [Tissue oxygen metabolism and cellular injury in patients with septic multiple organ failure (SMOF)]. AB - The present study was undertaken to study the pathophysiology of SMOF from the aspect of tissue hypoxia. Seventeen postoperative SMOF patients (9 survivors, 8 non-survivors) and 14 control ICU patients were evaluated their oxygen delivery (DO2I) and oxygen consumption (VO2I) in relation to cellular injury score (CIS) derived from 3 different intracellular metabolic indices, arterial ketone body ratio (AKBR), osmolality gap (OG) and blood lactate. In the early stage, SMOF patients showed hyperdynamic state and increased VO2I, reflecting increased oxygen demand in tissue. However, CIS of SMOF was significantly higher than that of control in spite of increased VO2I, indicating relative tissue hypoxia might exist in vital organs resulting in cellular injury. Further deterioration of CIS was accompanied with decreased VO2I. These data suggest that impaired tissue oxygen metabolism correlates with cellular injury and might be one of mechanisms of organ failure in SMOF patients. PMID- 8341241 TI - [Surgical stress induces the secretion of alpha human atrial natriuretic peptide]. AB - The changes in plasma alpha-hANP level and the factors affecting its secretion were studied in 35 patients treated by surgery for gastrointestinal disease (laparotomy group, 17) and (non-laparotomy group, 18). They did not have any particular complication during the study period. alpha-hANP, catecholamine (CA), antidiuretic hormone (ADH), aldosterone and plasma renin activity (PRA) were determined serially before and after the surgery. Plasma alpha-hANP level elevated on the post-operative day 1 and dropped to the upper limit of the normal range by the day 3, then gradually recovered to the level of before surgery. This early elevation of alpha-hANP was more marked in the laparotomy group than in the non-laparotomy group. These change in alpha-hANP level correlated well to those of CA, but not to those of ADH, aldosterone, and PRA. Age, sex, duration of surgery, bleeding and infusion volume during surgery did not affect the difference in alpha-hANP secretion between the two groups. In conclusion, the early elevation of plasma alpha-hANP level was correlated well to the surgical stress, and that this alpha-hANP secretion might be induced by CA secretion. PMID- 8341242 TI - [The surgical management of blunt liver trauma]. AB - One hundred and sixty-six consecutive patients with closed hepatic injury admitted to Osaka University Hospital from 1966 to 1990 were reviewed to evaluate the surgical procedures for injured liver. Of the 166 patients, 37 died within 24 hours of initial management. Thirteen (35%) of the 37 died related to exsanguinating hemorrhage of liver injury. Emergency laparotomy required hepatic resection in all and revealed hepatic vein or retrohepatic caval injuries in 9. Eighty-nine of 129 patients who survived over 24 hours of initial management underwent emergency laparotomy. Twenty-two of the 129 died thereafter. Five (3 underwent lobectomy and 2 simple suture) died of liver injury-related complications. Perihepatic packing was performed in 5 and all except for 2 of brain death were alive. Most complications except for hemobilia were well resolved. CT scan study revealed profoundly radiating injuries closed to spine in 63% and suggested existence of hepatic vein or caval injury. Especially, 20 of 31 CT studies (65%) in conservative management of liver injury showed the same findings with intact capsule. These results support that exsanguinating hemorrhage from deep injury including hepatic vein or vena cava is the most lethal but can be controlled with liver packing in a similar mechanism to liver trauma in conservative management. PMID- 8341243 TI - [Outcome of surgical treatment for Graves's disease and a correlation between its clinical course and values of TSH receptor antibodies (TRAb)]. AB - Two hundreds and sixteen patients with Graves' disease who underwent subtotal thyroidectomy at Ito Hospital during 1983 and 1984 were studied in order to known about the relationship between the prognosis and preoperative values of TRAb. There were 65 euthyroid patients (30.1%), 112 hypothyroid (51.8%), and 39 hyperthyroid (18.1%). No relationship between postoperative thyroid function and preoperative values of TRAb was observed. Postoperative values of TRAb were significantly higher in hyperthyroid group than in euthyroid group and hypothyroid group at any period. Postoperative values of TRAb were negative in about 90% of the patients of euthyroid group. On the other hand, negative postoperative values of TRAb were also observed in about 40% patients of hyperthyroid group. It is concluded that postoperative thyroid function could not be estimated from preoperative values of TRAb and much care is thought to be necessary to estimate the prognosis from postoperative values of TRAb. PMID- 8341244 TI - [Peri- and postoperative management in one staged operation of cardiac disease combined with pectus excavatum]. AB - Patients with pectus excavatum occasionally have coexisting surgical heart disease. During a 10-year period up to the end of 1988, we surgically treated a total of 2015 cases of pectus excavatum, including 12 cases with one staged operation for pectus excavatum and heart disease. Proving the advantage of our one staged operation for the coexisting diseases we studied data resulting from the perioperative management in the group of one staged operations (n = 5), and in the other group of single valve replacement (n = 10). Operative time, amount of operative blood loss and total amount of transfused blood, were 433 +/- 66 min. (mean +/- SD), 3180 +/- 1867 ml and 4836 +/- 2247 ml, in the former group (n = 5), respectively. These data were almost similar to those in the latter group (n = 10). Postoperative ventilatory support time and ICU stay time also showed little difference between two groups. We conclude these data supports our previous report that one staged operation has no perioperative disadvantage in the surgical treatment of patients with both cardiac disease and pectus excavatum. PMID- 8341245 TI - [Intraoperative assessment of left ventricular function with left ventricular pressure-volume relationships in patients with open heart surgery]. AB - There are few reports on the assessment of the left ventricular function from left pressure-volume relationships intraoperatively in open heart surgery. LV Emax, Ea/Ees and EW/PVA efficiency were assessed intraoperatively by using a left ventricular conductance catheter in patients with aortocoronary bypass. After dobutamine administration (DOB, 10 micrograms/kg/min), LV Emax was increased by 33 +/- 23% during cardiopulmonary bypass (CPB) and 60 +/- 38% after weaning from CPB. Ea/Ees changed from 2.14 +/- 1.36 to 1.08 +/- 0.47 after weaning from CPB with dobutamine administration. EW/PVA efficiency changed from 52 +/- 12% to 66 +/- 10%. The change of LV Emax after dobutamine administration was correlated with the change of LV Emax after weaning from CPB and was correlated with Ea/Ees and EW/PVA efficiency after weaning from CPB. We concluded that measuring LV Emax before and after dobutamine administration during CPB is useful to assess left ventricular contraction clinically. PMID- 8341246 TI - [Resected roentgenographically occult bronchogenic squamous cell carcinoma tumor size, survival and recurrence]. AB - The relationship between tumor size and nodal involvement of resected roentgenographically occult squamous cell carcinoma in 127 cases was documented. Survival and recurrent patterns were analyzed. Intrabronchial invasion was observed in 103 cases and extrabronchial invasion in 24 cases. One hundred and nineteen cases (94%) had N0 diseases, six (5%) N1 diseases and two (2%) N2 diseases. One hundred and one cases were in early stage and 26 in non-early stage. Nodal involvement was observed in two (2%) of the 103 cases with intrabronchial invasion and in six (25%) of the 24 cases with extrabronchial invasion. Nodal involvement was noted in none (0%) of 55 cases in whom longitudinal extension of tumors was within 10mm, but was noted in four (9%) of 46 cases in whom it was 11 to 20mm and in four (15%) of 26 cases in whom it was 21 to 55mm. Death from primary lung cancer occurred in three (12%) of the non early cases, but in none (0%) of the early cases. Death from multiple metachronous lung cancer occurred in one (4%) of the non-early cases and in three (3%) of the early cases. Nodal and extrabronchial involvement reduced survival. Recurrence often involved hilar, mediastinal, supraclavicular nodes, and surgical margin of bronchus. PMID- 8341247 TI - [The influence of cholesterol feeding on the anastomotic region of the induced atherosclerotic rabbit vessels--especially on the late occlusive process]. AB - Late occlusive complication of implanted graft may occur 6 months to 5 years after operation. The most frequent cause of this condition is considered to be an intimal thickening at the anastomotic sites. The relationship between this intimal thickening and cholesterol feeding in rabbits was investigated. Twenty eight male New Zealand White Rabbits were assigned following 4 groups. Group 1: given 0.1% cholesterol containing rabbit pellets after denudation of endothelium Group 2: given standard laboratory rabbit pellets after denudation Group 3: given 0.1% cholesterol rabbit pellets without denudation Group 4: given standard rabbit pellets without denudation Anterior half of infrarenal abdominal aorta of all rabbits was incised and then continuous over and over suture was carried out. Three months later, rabbits were killed and specimens were obtained. In group 1, 3 specimens out of 7 were found significant intimal thickening near anastomosis, whereas, in group 2 specimens showed regular thickening which seemed to be affected by denudation of endothelium. In group 3, intimal thickening localized only near anastomosis was found. From these results, we concluded intimal thickening at the anastomotic sites can be considered as the initial stage of atherosclerosis and cholesterol would be one of the important factors which promote this thickening. PMID- 8341248 TI - [A case of postpartum silent thyroiditis misapprehended as malignant lymphoma of the thyroid]. AB - A case of postpartum silent thyroiditis misapprehended as malignant lymphoma of the thyroid is reported. The patient was a 30-year-old female who had received irradiation therapy to the neck for malignant lymphoma 9 years ago. She was referred to our department owing to a struma accompanying rapid aggravation of chronic thyroiditis after delivery. The mechanism of this case was possible to be explained by immune rebound theory. It was difficult to make differential diagnosis of this case from malignant lymphoma of the thyroid clinically and cytologically when immune rebound phenomena with invasion of lymphocyte and appearance of lymph follicle were the strongest. Immune state of the patients with chronic thyroiditis accompanied by morphological change should be taken into consideration in the process of making diagnosis of malignant lymphoma of the thyroid. PMID- 8341249 TI - [Successful operation for two cases of an aneurysmal bone cyst of the rib]. AB - An aneurysmal bone cyst involving the rib is very rare. A 43-year-old man and 49 year-old woman complained of pain and swelling on the chest. X-ray and CT revealed a local expansion and honeycomb lesion of the right 9th rib. Surgical excision of the rib were performed to remove the tumor completely. The histopathological examination revealed that the lesion consisted of many cavities filled with blood and trabecullae containing osteoid tissue and giant cells, showing it to be an aneurysmal bone cyst. Because of the potential for the rapid growth and difficulty in differentiation between benign and malignant rib tumor, an excisional biopsy should be considered for the treatment of an aneurysmal bone cyst of the rib. PMID- 8341250 TI - [Delayed surgical treatment of traumatic injury of the thoracic aorta]. AB - A 55-year-old male, who had fallen down from a tree, was brought into the emergency room. The initial roentogenogram of the chest showed widening of the mediastinum, but CT study did not give the blood leaking out of the aorta. Thus the patient was managed in ICU. An aortography showed an aneurysmal dilatation of the descending aorta on ninth day after the injury, but we interpreted it may not proceed to the free rupture. Therefore we postponed the operation of the aortic injury until 41 days after the trauma. Immediate repair may be thought to be the first choice for acute traumatic injury of the thoracic aorta, but delayed surgery can be achieved safely on selective patients. PMID- 8341251 TI - [A case of venous aneurysm]. AB - A 70-year-old woman was referred to our hospital with a complaint of a soft mass at the right elbow. Venography demonstrated that the mass was connected with vein. This mass was surgically removed and histologically a marked reduction of both elastic fibers and the adventitia were observed in the aneurysmal wall. Venous aneurysm (VA) is different form varicose veins by many features. It was considered that congenital fragility of the venous walls was associated with the onset of VA. We classified VA into type-I VA (cystic ectasia) and type II (fusiform ectasia). PMID- 8341252 TI - [Three dimensional cholangiography with spiral CT for analysis of biliary tract: preliminary report]. PMID- 8341253 TI - [Modulation by 1-leucovorin of 5-fluorouracil antitumor activity on human gastric carcinoma xenograft in nude mouse: preliminary report]. PMID- 8341254 TI - [Immunohistochemical investigations of proliferating tissues at anastomotic sites in saphenous vein grafts: preliminary report]. PMID- 8341255 TI - Low-temperature-dependent expression of a rice gene encoding a protein with a leucine-zipper motif. AB - We have isolated from rice suspension cells three non-sequence-related cDNAs the expression of which is markedly induced by low, non-freezing temperature. Here we further characterize one of the cDNA clones, lip19. Expression of lip19 is positively regulated by low temperature, but not affected by high (40 degrees C) temperature. Sequencing and primer extension analyses showed that lip19 has a long (552 bp) 5' non-coding sequence followed by a single open reading frame specifying a protein of 148 amino acids. The deduced amino acid sequence of the protein, Lip19, shows at its amino-terminus a conserved basic region followed by a "leucine-zipper" domain. The reported sequence most similar to Lip19 is maize OCSBF-1, which is a bZip-type DNA binding protein. The possibility is suggested that Lip19 is a transcriptional factor that is positively controlled by low temperature. PMID- 8341256 TI - Domains of colicin M involved in uptake and activity. AB - Colicin M inhibits murein biosynthesis by interfering with bactoprenyl phosphate carrier regeneration. It belongs to the group B colicins the uptake of which through the outer membrane depends on the TonB, ExbB and ExbD proteins. These colicins contain a sequence, called the TonB box, which has been implicated in transport via TonB. Point mutations were introduced by PCR into the TonB box of the structural gene for colicin M, cma, resulting in derivatives that no longer killed cells. Mutations in the tonB gene suppressed, in an allele-specific manner, some of the cma mutations, suggesting that interaction of colicin M with TonB may be required for colicin M uptake. Among the hydroxylamine-generated colicin M-inactive cma mutants was one which carried cysteine in place of arginine at position 115. This colicin derivative still bound to the FhuA receptor and killed cells when translocated across the outer membrane by osmotic shock treatment. It apparently represents a new type of transport-deficient colicin M. Additional hydroxylamine-generated inactive derivatives of colicin M carried mutations centered on residues 193-197 and 223-252. Since these did not kill osmotically shocked cells the mutations must be located in a region which is important for colicin M activity. It is concluded that the TonB box at the N terminal end of colicin M must be involved in colicin uptake via TonB across the outer membrane and that the C-terminal portion of the molecule is likely to contain the activity domain. PMID- 8341257 TI - Promoter specificity and deletion analysis of three heat stress transcription factors of tomato. AB - Transient expression assays in transformed tobacco (Nicotiana plumbaginifolia) mesophyll protoplasts were used to test the activity of three tomato heat stress transcription factors, HSF24, HSF8 and HSF30, in a trans-activation and a trans repression assay. The results document differences between the three HSFs with respect to their response to the configuration of heat stress promoter elements (HSEs) in the reporter construct (promoter specificity) and to the stress regime used for activation. Analysis of C-terminal deletions identified acidic sequence elements with a central tryptophan residue, which are important for HSF activity control. Surprisingly, heterologous HSFs from Drosophila and human cells, but not from yeast, were also functional as heat stress-induced transcription factors in this tobacco protoplast system. PMID- 8341258 TI - A family of serine protease genes expressed in adult buffalo fly (Haematobia irritans exigua). AB - Gene fragments encoding serine proteases expressed in adult buffalo fly (Haematobia irritans exigua) were amplified from cDNA using generic oligonucleotide PCR primers, based on conserved residues surrounding the active site His and Ser amino acids found in all serine proteases. The PCR product consisted of a broad band extending from about 450 bp to 520 bp, which suggested that the PCR product actually consisted of numerous DNA fragments of slightly variable sizes. Seventeen independent clones of these fragments, each with an insert of approximately 480 bp, were digested with HaeIII. Comparison of restriction fragment patterns indicated that 13 of these clones harboured different PCR products. This was confirmed by DNA sequence analysis of 9 clones. Each of the sequenced clones contained an open reading frame which included structurally conserved regions characteristic of the serine protease superfamily. This study reveals the expression of a large and highly variable repertoire of serine proteases in adult buffalo fly. Importantly, these data also demonstrate the utility of such an approach in obtaining DNA probes for use in further investigations of gene family organization and expression, as well as providing recombinant antigens in the form of fusion proteins which may be used as candidates for vaccine production. PMID- 8341259 TI - The heterodimeric protease clostripain from Clostridium histolyticum is encoded by a single gene. AB - Clostripain (EC 3.4.22.8) is a heterodimeric cysteine endopeptidase with strict specificity for Arg-Xaa peptidyl bonds. It is secreted by Clostridium histolyticum strains. For the first time we present evidence that both polypeptide chains of native clostripain are encoded by a single gene. DNA sequencing of two overlapping genomic DNA fragments revealed a single open reading frame (ORF) of 1581 nucleotides encoding a polypeptide of 526 amino acid residues. The ORF is preceded by canonical transcription signals and both chains of the clostripain heterodimer are completely represented by the deduced coding sequence. Most interestingly, the sequences coding for the light and the heavy chain are joined by a DNA stretch coding for a linker nonapeptide that is preceded by the C-terminal arginyl residue of the light chain and also ends with an arginyl residue. Heterologous expression of the gene in Escherichia coli yielded an enzyme capable of hydrolyzing the clostripain substrates N alpha benzoyl-L-arginine ethyl ester (BAEE) and N-carbobenzoxy-L-arginine p nitroanilide (Z-Arg-pNA). PMID- 8341260 TI - Saccharopolyspora hirsuta 367 encodes clustered genes similar to ketoacyl synthase, ketoacyl reductase, acyl carrier protein, and biotin carboxyl carrier protein. AB - The actI gene, encoding a component of the actinorhodin polyketide synthase of Streptomyces coelicolor, was used to identify and clone a homologous 11.7 kb BamHI DNA fragment from Saccharopolyspora hirsuta 367. The cloned fragment complemented actinorhodin production in a strain of Streptomyces coelicolor bearing a mutant actI gene. The DNA sequence of a 5.1 kb fragment revealed 6 open reading frames (ORF). ORF1 does not resemble any known DNA or deduced protein sequence, while the deduced protein sequence of ORF2 resembles that of biotin carboxyl carrier proteins. Based on the similarity to deduced protein sequences from cloned genes of polyketide producers, ORF3 would code for a ketoreductase, ORF4 and ORF5 for the putative heterodimeric beta-ketoacyl synthase, and ORF6 for an acyl carrier protein. PMID- 8341261 TI - Isolation and characterization of mutants with impaired regulation of rpsA, the gene encoding ribosomal protein S1 of Escherichia coli. AB - In order to select mutants that would help to characterize the post transcriptional regulation of rpsA, we constructed a strain in which the growth rate on lactose minimal medium is determined by the amount of an rpsA-lacZ' alpha fragment fusion protein produced, even when this is encoded by a high-copy-number plasmid. In the parental strain, synthesis of the fusion protein is repressed by a wild-type rpsA gene, present on a compatible plasmid. Twenty-eight spontaneous and independent mutants, all of them mapping in the rpsA leader region, were isolated as strains that showed higher growth rates, on lactose medium, due to increased synthesis of the rpsA-lacZ' fusion protein. Among these mutants only three sequence changes were found, mapping 9, 10 and 27 bases upstream of the rpsA start codon. At both the -9 and -10 positions an A to G transition and at 27 a C to G transversion all resulted in a sequence with better complementarity to the 3' end of 16S rRNA. We also isolated two mutations mapping in the plasmid encoded rpsA structural gene: an ochre nonsense mutation in codon 15 of the rpsA gene and a frameshift mutation, deleting the T residue at position +1186. To facilitate the in vitro assay of alpha-fragment activity we also constructed a strain that overproduces the alpha-acceptor fragment four-fold relative to a strain that is diploid for this lacZ delta M15 allele. PMID- 8341262 TI - Cloning and characterization of the gamma-glutamyl phosphate reductase gene of Campylobacter jejuni. AB - The gamma-glutamyl phosphate reductase gene, proA, of Campylobacter jejuni was isolated from a recombinant pBR322 clone. A HindIII fragment of the insert containing the gene was subcloned into pUC19 and sequenced in both orientations. The deduced amino acid sequence of gamma-glutamyl phosphate reductase (EC 1.2.1.41) of C. jejuni exhibits 36.4% identity to that of Escherichia coli and 36.0% identity to Serratia marcescens. Two highly conserved regions in the amino acid sequence were identified from the alignment of the three available gamma glutamyl phosphate reductase gene sequences. The gene was expressed from its own promoter and the transcription start site was mapped. The proline biosynthetic genes of C. jejuni are not located tandemly and thus differ in this respect from those of E. coli and S. marcescens, where gamma-glutamyl phosphate reductase and gamma-glutamyl kinase (proB) are located in a single operon. PMID- 8341263 TI - Budding yeast mutants showing constitutive basal levels of expression of DNA synthesis genes. AB - Two mutants have been isolated in Saccharomyces cerevisiae in which transcripts from at least CDC8, CDC9, CDC21 (TMP1) and POL1 genes are expressed constitutively in cells blocked at START by use of either alpha-pheromone or the cdc28 mutation. The transcripts from these genes also persist in mutant stationary phase cells; however, cell cycle regulation of these four DNA synthesis genes occurs normally in late G1. The mutation therefore does not appear to lie in the MCB-DSC1 (MBF) system that controls the periodic regulation of the genes, but must affect some control mechanism regulating basal levels of expression. PMID- 8341264 TI - A nucleotide substitution in one of the beta-tubulin genes of Trichoderma viride confers resistance to the antimitotic drug methyl benzimidazole-2-yl-carbamate. AB - We characterized a Trichoderma viride strain that is resistant to the antimitotic drug methyl benzimidazole-2-yl-carbamate (MBC). This species has two beta-tubulin genes (tub1 and tub2) and by reverse genetics we showed that a mutation in the tub2 gene confers MBC resistance in this strain. Comparison of the tub2 sequence of the mutant strain with that of the wild type revealed that a single amino acid substitution of tyrosine for histidine at a position 6 is responsible for the MBC tolerance. Furthermore, we showed that this gene can be used as a homologous dominant selectable marker in T. viride transformation. Both tubulin genes were completely sequenced. They differ by 48 residues and the degree of identity between their deduced amino acid sequences is 86.3%. PMID- 8341265 TI - Chitin synthetase mutants of Phycomyces blakesleeanus. AB - Mutants resistant to nikkomycin, an inhibitor of chitin biosynthesis, were isolated after exposure of wild-type spores of the fungus Phycomyces blakesleeanus to N-methyl-N'-nitro-N-nitrosoguanidine. Genetic analysis revealed that nikkomycin resistance was due to mutations in a single gene, chsA. Mutants and wild type grew equally well in the absence of nikkomycin. In contrast to the wild type, whose spore germination and mycelial growth were inhibited by 5 microM nikkomycin, chsA mutants grew reasonably well in the presence of 50 microM nikkomycin. Chitin synthesis in vivo was much less affected by the drug in the mutants than in the wild type. Resistance was not due to impaired uptake or detoxification of the drug. Analysis of the kinetics of chitin synthesis in vitro showed that the mutants had a decreased Ka for the allosteric activator, N acetylglucosamine, and gross alterations in nikkomycin inhibition kinetics. These results indicate that chsA is the structural gene for chitin synthetase, or at least for the polypeptide that bears the catalytic and allosteric sites. PMID- 8341266 TI - A cloned angiotensin receptor isoform from the turkey adrenal gland is pharmacologically distinct from mammalian angiotensin receptors. AB - A 2046-base pair cDNA clone, homologous to mammalian angiotensin (AT) AT1 receptors, was isolated from a library prepared from adrenal glands of the domestic turkey (Meleagris gallopavo). Sequence analysis of the cDNA insert in clone pTAT2' reveals a 1077-base pair open reading frame predicting a 359-amino acid protein approximately 75% homologous to mammalian AT1 receptors. Saturation radioligand binding studies performed in membranes of COS-7 cells transfected with pTAT2' show high affinity specific binding of 125I-angiotensin II, with a Kd of 172 pM. The rank order of affinities for a series of ligands determined by competition binding studies is angiotensin II > or = [Sar1,Ile8]-angiotensin II > angiotensin III approximately [Sar1,Ala8]-angiotensin II approximately CGP42112A > angiotensin I > Dup753 > PD123177. This rank order of affinity series differs substantially from that for mammalian AT1 receptors and AT2 binding sites. Angiotensin II (100 nM) can stimulate inositol phosphate production similarly in COS-7 cells transfected with pTAT2' and in COS-7 cells transfected with the AT1a receptor cDNA pCa18b. This response in pTAT2'-transfected cells is not attenuated in the presence of 30 microM Dup753. In contrast, this concentration of antagonist attenuates > 90% of the inositol phosphate response to angiotensin II in COS-7 cells transfected with the rat AT1a receptor cDNA. These results demonstrate an avian structural homologue of mammalian AT1 receptors possessing distinct pharmacological properties with both peptide and nonpeptide AT receptor ligands. PMID- 8341267 TI - Measurement of guanine nucleotide-binding protein activation by A1 adenosine receptor agonists in bovine brain membranes: stimulation of guanosine-5'-O-(3 [35S]thio)triphosphate binding. AB - Signal transduction by A1 adenosine receptors was investigated by measuring the modulation by adenosine agonists of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTP[S]) binding to guanine nucleotide-binding proteins (G proteins). The extent of stimulation of [35S]GTP[S] binding was dependent on the presence of high concentrations of Mg2+ (1-10 mM), GDP (10 microM), and NaCl (100 mM). Under optimal conditions, the agonist (R)-N6-phenylisopropyladenosine [(R)-PIA] stimulated binding of [35S]GTP[S] to G proteins approximately 2.3-fold. All adenosine receptor agonists tested stimulated the binding of [35S]GTP[S] with a rank order of potency typical of A1 adenosine receptors in bovine tissues, (R) PIA > 2-chloro-N6-cyclopentyladenosine > (S)-PIA > 5'-N-ethylcarboxamidoadenosine > 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosin e. The EC50 values for G protein activation correlated with the Ki value of agonists for inhibition of radioligand binding to the high affinity state of the A1 adenosine receptor. The inclusion of 100 mM NaCl as well as increasing GDP concentrations led to a parallel increase of Ki values and EC50 values. In addition, both compounds induced a shift of A1 adenosine receptors from the high affinity state for agonists to the low affinity state. PMID- 8341268 TI - Mutations leading to antifolate resistance in Chinese hamster ovary cells after exposure to the alkylating agent ethylmethanesulfonate. AB - Chinese hamster ovary cells with a single allele for dihydrofolate reductase were used as a model system to study the effect of exposure to an alkylating agent, ethylmethanesulfonate, on rates and types of mutations at the dihydrofolate reductase locus leading to antifolate resistance. After overnight exposure to 400 micrograms/ml ethylmethanesulfonate, cells were allowed to recover for 3 days, and resistant colonies were selected in 8 x 10(-8) M trimetrexate. Trimetrexate, rather than methotrexate, was used as the selecting agent to increase the probability of obtaining mutations in dihydrofolate reductase, rather than in the reduced folate transport carrier protein. Seven of several hundred surviving colonies were selected at random, and cell lines were established. Cell lines 1-3 were maintained in culture in the presence of 8 x 10(-8) M trimetrexate and were 66-170-fold resistant to the drug. Cell lines 4-7 were initially expanded in 8 x 10(-8) M trimetrexate but were then maintained in the absence of the drug. These cell lines were 4.4-26-fold resistant to the drug, compared with the parental cell line. Cell line 1 was found to have an increase in dihydrofolate reductase activity, a corresponding increase in mRNA for dihydrofolate reductase, and amplification of this gene. Cell lines 2 and 6 had a mutated dihydrofolate reductase with altered trimetrexate- and methotrexate-binding properties. Cell line 3 had a 3-fold increase in dihydrofolate reductase activity. In cell lines 4, 5, and 7 the mechanisms of resistance to trimetrexate remain unknown. PMID- 8341269 TI - Novel endothelin receptors in the follicular membranes of Xenopus laevis oocytes mediate calcium responses by signal transduction through gap junctions. AB - Follicular oocytes from Xenopus laevis display saturable and high affinity endothelin (ET)-1 binding sites. Competition binding experiments using unlabeled ET-1, ET-3, and sarafotoxin 6c indicated that these ET receptors belong to the ETA receptor subtype. However, the ETA receptor-selective antagonist BQ123 [cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu)] failed to inhibit 125I-ET-1 binding to these receptors, suggesting that these receptors belong to a novel subtype of ETA receptors (ETAX) distinct from the human ETA receptors. These endogenous receptors are present in the follicular layer, because defolliculated oocytes did not show any 125I-ET-1 binding. Addition of ET-1 to follicular oocytes led to Ca2+ mobilization, which was reversibly blocked by treatments that uncouple gap junctions, suggesting that these ETAX receptors mediate their response by transferring signals through gap junctions. On the other hand, the expressed human ETA receptor-mediated Ca2+ mobilization was not blocked by inhibitors of gap junctions. In agreement with the binding data, the endogenous ETAX receptor mediated response was not inhibited by BQ123 even at 100 nM, whereas the expressed human ETA receptor-mediated response was inhibited by 50% at concentrations as low as 10 nM. This further confirms that the amphibian ETAX receptors are different from mammalian ETA receptors. Finally, ET-1 enhanced the rate of progesterone-induced maturation of follicular oocytes, implying the involvement of these endogenous ETAX receptors in an in vivo maturation process. PMID- 8341270 TI - Endothelin- and ATP-induced inhibition of adenylyl cyclase activity in C6 glioma cells: role of Gi and calcium. AB - Endothelin-1 (ET) and ATP mobilize Ca2+ in rat C6 glioma cells by stimulating phosphoinositide turnover. Both agents also inhibit adenylyl cyclase (AC) activity in C6 glioma cells. The goal of this study was to characterize the molecular mechanisms responsible for the inhibition of AC activity. The administration of either ET, ATP, A23187, or thapsigargin to cells simultaneously with isoproterenol for 5 min inhibited isoproterenol-stimulated cAMP synthesis by a maximum of 60%, 91%, 65%, and 68%, respectively. Pretreatment of cells with pertussis toxin (PTX) did not alter the inhibitory effects of A23187 or thapsigargin, whereas the inhibitory effects of ET or ATP were completely eliminated. Removal of extracellular Ca2+ and 1,2-bis(2-aminophenoxy)ethane N,N,N',N'- tetraacetic acid acetoxymethyl ester treatment failed to affect the inhibition caused by ET or ATP, whereas the inhibition caused by A23187 or thapsigargin was completely eliminated in Ca(2+)-free medium and was attenuated by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester treatment. The inhibition by both receptor agonists in the earlier phase (30 sec) of the AC reaction was, however, reduced by using either Ca(2+)-free medium or PTX pretreatment. The administration of 3-isobutyl-1-methylxanthine or Ro 20-1724 suggested that the inhibitory effects of A23187 and thapsigargin were partially due to Ca(2+)-dependent stimulation of PDE activity. Short term treatment with phorbol-12-myristate-13-acetate (PMA) had no effect on isoproterenol-stimulated AC activity. However, the inhibition of cAMP induced by ET or ATP, but not by A23187 or thapsigargin, was diminished by PMA, suggesting that the receptor signal via Gi was blocked by PMA treatment. The antagonistic effect of PMA was blocked by staurosporine. All four agents still inhibited AC activity in cells that had been treated with PMA for 24 hr to deplete protein kinase C. ET produced an additional decrease in AC activity in cells that had been treated with a maximally effective concentration of A23187 or thapsigargin. The ET- or ATP induced decrease in cAMP levels showed homologous desensitization. These results demonstrate that ETZ receptors and ATP receptors in C6 glioma cells inhibit AC activity primarily by interaction with a PTX-sensitive G(i) and partially by elevation of [Ca(2+)]. Protein kinase C activation is not responsible for agonist induced inhibition of AC but appears to uncouple the G(i)/AC system activated by ET or ATP. PMID- 8341271 TI - Barium blockade of a clonal potassium channel and its regulation by a critical pore residue. AB - Barium ion (Ba2+) has the same crystal radius as potassium ion but blocks rather than permeates the ion-conducting pore of K+ channels. Ba2+ ion may therefore be used as a probe of residues lining the pore of K+ channels, and we applied it to test the position and function of a residue crucial for K+/Rb+ selectivity and blockade by internal tetraethylammonium. We examined blockade by internal and external Ba2+ of the delayed rectifier K+ channel DRK1 (Kv2.1) and tested the effects of point mutations at pore residue 374. Internal Ba2+ blocked the wild type open channel with high affinity (Kd = 13 microM). Blockade involved more than one site, was voltage dependent, and increased at more positive potentials. Mutation of V374 to threonine or serine produced a significant decrease in the rate of dissociation of internal Ba2+ from the pore, whereas mutation of V374 to isoleucine produced no change. For wild-type channels, external Ba2+ decreased the rate of activation of the K+ current, suggesting that Ba2+ can interact with closed DRK1 channels. This result was unaffected by the V374T substitution. Furthermore, external Ba2+ also caused a very low affinity (Kd approximately 30 mM) and voltage-independent block of the open DRK1 channel. Thus, Ba2+ blocked the pore at internal and external sites, which were clearly distinguishable. The effects of substitution at position 374 with residues having polar hydroxyls are consistent with position 374 being at a surface position critical for ion permeation, near the inner mouth of the pore. PMID- 8341272 TI - Transport of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea in the human glioma cell line SK-MG-1 is mediated by an epinephrine-sensitive carrier system. AB - The transport of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU), an experimental anticancer compound, was investigated in the human glioma cell line SK-MG-1. The transport of [3H]SarCNU was examined in suspension. The uptake of [3H] SarCNU was found to be temperature dependent, with influx being linear to 4 sec at 37 degrees. Equilibrium was reached after 1 min at 22 degrees and 37 degrees, with accumulation slightly above unity. SarCNU was not significantly metabolized in the cells after a 60-min incubation at 37 degrees, as shown by thin layer chromatography. At 37 degrees, uptake of [3H]SarCNU was found to be saturable, sodium independent, and energy independent. Previous work demonstrated that SarCNU was able to inhibit the uptake of sarcosinamide, which is transported by the catecholamine uptake 2 system. This catecholamine system mediates the physiological transport of epinephrine. Epinephrine was able to significantly inhibit the uptake of [3H]SarCNU, at a concentration of 50 microM, by 40%. Additionally, several amino acids were unable to inhibit the uptake of SarCNU. The initial rate of SarCNU influx is mediated by both facilitated and nonfacilitated diffusion. The nonfacilitated diffusion rate could be estimated from the linear concentration dependence of the residual influx rate for SarCNU, which was not inhibited by the presence of excess co-permeant (epinephrine). Dixon plot analysis, corrected for nonfacilitated diffusion of SarCNU, revealed that epinephrine inhibited the uptake of SarCNU competitively, with a Ki of 163 +/- 15 microM, a value similar to the Km value for epinephrine influx in SK-MG-1 cells. Additionally, after appropriate corrections for nonfacilitated diffusion in the influx rates observed for SarCNU, it was revealed that SarCNU influx obeyed Michaelis-Menten kinetics over a 200-fold range of concentrations, with a Km of 2.39 +/- 0.37 mM and a Vmax of 236 +/- 53 pmol/microliters of intracellular water/sec. Metabolic poisons (2,4-dinitrophenol, iodoacetate, NaCN, NaF, or ouabain) were unable to inhibit the influx of SarCNU, suggesting that the carrier mediated uptake of SarCNU is energy independent and mediated by facilitated diffusion. These findings indicate that SarCNU uptake in SK-MG-1 cells is mediated both by nonfacilitated diffusion and by facilitated diffusion via the catecholamine uptake 2 carrier system. SarCNU is the first chloroethylnitrosourea that has been demonstrated to have carrier-mediated uptake. Moreover, this carrier-mediated uptake may play a role in the increased cytotoxicity of SarCNU against gliomas, compared with that of 1,3-bis(2,-chloroethyl)-1-nitrosourea, which enters cells primarily by passive diffusion. PMID- 8341273 TI - Role of NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase) in activation of mitomycin C under acidic conditions. AB - The quinone antitumor agent mitomycin C is preferentially toxic to some cells under hypoxic and acidic conditions. The two-electron reducing enzyme DT diaphorase may be a major contributor to mitomycin C activation under aerobic conditions, but its role in drug activation under hypoxic and acidic conditions is unclear. In this study, we observed that mitomycin C produced increased DNA cross-linking and cytotoxicity in Chinese hamster ovary cells at pH 6.6, compared with pH 7.2, under aerobic conditions, but drug activity was similar at these pH values under hypoxic conditions. The DT-diaphorase inhibitor dicoumarol completely inhibited the enhanced activity of mitomycin C at acidic pH under aerobic conditions but had no effect on DNA cross-linking or cytotoxicity under hypoxic conditions. These finding suggest that the enhanced activity of mitomycin C at acidic pH, in air, is due to increased drug activation by DT-diaphorase. However, the role of DT-diaphorase in activating mitomycin C under hypoxic conditions appears to be limited, even at acidic pH. PMID- 8341274 TI - Characterization of human liver microsomal cytochrome P450 involved in the reductive metabolism of zonisamide. AB - Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) was metabolized to 2 sulfamoylacetylphenol (SMAP) in human liver microsomes under anaerobic conditions. The formation of SMAP was remarkably inhibited by cimetidine, n octylamine, ketoconazole, and carbon monoxide, indicating that a cytochrome P450 is involved in the metabolism of zonisamide to SMAP in human liver microsomes. The SMAP-producing activity did not correlate with the spectrally determined amount of cytochrome P450. In contrast, the SMAP-producing activity from zonisamide correlated closely with the activity of testosterone 6 beta hydroxylase (r2 = 0.96) and correlated slightly but significantly with the activity of imipramine 2-hydroxylase (r2 = 0.28), but not with those of aniline hydroxylase (r2 = 0.09) or benzphetamine N-demethylase (r2 = 0.20). In addition, immunoquantitation of cytochrome P450 enzymes in 21 human liver microsomal samples revealed that SMAP formation correlated closely with the amount of P450 3A enzyme and correlated moderately well with that of P450 2D6 but not with that of P450 2C enzyme in human liver microsomes. P450 3A4 exhibited SMAP-producing activity in a reconstituted monooxygenase system. The metabolism of zonisamide to SMAP was almost completely inhibited by anti-P450 3A4 antibody but not by anti P450 2C9 or anti-P450 2D6 antibodies, suggesting that the amount of P450 3A enzyme may be a major factor influencing the level of metabolism of zonisamide to SMAP in human liver microsomes. PMID- 8341275 TI - 5-Fluorouracil alters dihydrofolate reductase pre-mRNA splicing as determined by quantitative polymerase chain reaction. AB - A quantitative polymerase chain reaction (PCR) assay has been developed to determine the absolute and relative amounts of each dihydrofolate reductase RNA species present at different stages of splicing (i.e., pre-mRNA, splicing intermediate, and mRNA). The ratios of each RNA species as measured by quantitative PCR have been confirmed by S1 nuclease mapping analysis. Quantitative PCR studies reveal a concentration-dependent decrease in the levels of dihydrofolate reductase mRNA and a splicing intermediate but little change in pre-mRNA levels after long term exposure of cells to 5-fluorouracil (FUra). The observed changes correlate with the extent of FUra incorporation into RNA and with cytotoxicity. These results, together with previous data from our laboratory, provide the first direct evidence that FUra incorporation into RNA can cause inhibition of pre-mRNA splicing in vivo. Inhibition of pre-mRNA splicing is thus a likely additional mechanism by which FUra incorporation into RNA may lead to growth inhibition and cell death. PMID- 8341276 TI - 5-Amino-4-imidazolecarboxamide riboside potentiates the metabolism and anti-human immunodeficiency virus activity of 2',3'-dideoxyinosine. AB - The antiviral activity of the purine dideoxynucleosides 2',3'-dideoxyadenosine (ddA) and 2',3'-dideoxyinosine (ddI) is dependent on their conversion into ddA triphosphate in vivo. 5-Amino-4-imidazolecarboxamide riboside (AICA riboside), a natural metabolite in purine biosynthetic pathways, is converted into IMP, a substrate for the biosynthesis of adenine and guanine nucleotides, and enhances the intracellular purine nucleotide pools. Because IMP also serves as a phosphate donor in the anabolic phosphorylation of ddI (and ddA) into ddI monophosphate by the cytosolic enzyme 5'-nucleotidase, we investigated the effects of AICA riboside on the phosphorylation and antiretroviral activity of these purine nucleoside analogs. At an AICA riboside concentration of 0.5 mM, there was a approximately 2-fold increase in the intracellular ATP and GTP levels, whereas a nearly 8-fold increase was observed for the phosphorylation of ddA (or ddI). A marked reduction in intracellular pools of the pyrimidine nucleotides CTP and UTP was observed in AICA riboside-treated cells and inhibited cell proliferation. However, this growth inhibition was prevented by the addition of uridine to the cultures. Cells pretreated with AICA riboside and ddI were less susceptible to human immunodeficiency virus (HIV) infection and synthesized reduced levels of HIV proviral DNA. A 10-fold potentiation of the effectiveness of ddI against both wild-type HIV (HIVIIIB) and a ddI-resistant variant HIV was observed in the presence of 0.5 mM AICA riboside. These results show that AICA riboside modulates the anabolism and antiviral activity of ddI, and they have implications for possible therapies with dideoxynucleosides. PMID- 8341277 TI - Commonly occurring plant flavonoids have estrogenic activity. AB - A remarkable diversity of naturally occurring and synthetic compounds have been shown to mimic the biological effects of 17 beta-estradiol by virtue of their ability to bind to and activate the nuclear estrogen receptor. This report extends the family of nonsteroidal estrogens to include several multiply hydroxylated chalcones, flavanones, and flavones. The hormone-like activity of these natural plant products is indicated by their ability to stimulate an estrogen receptor-dependent transcriptional response and to promote growth of estrogen-dependent MCF7 cells in culture. The transcriptional response can be inhibited by the steroidal estrogen antagonist ICI-164,384 and is specific for the estrogen receptor. Evidence is presented to show that selected hydroxylated flavonoids interact directly with the estrogen receptor, based on their ability to compete for the binding of 17 beta-[3H]estradiol to the receptor in cell-free extracts. These compounds are less active, on a molar basis, than 17 beta estradiol or the synthetic dihydroxystilbene estrogens, but they have potencies comparable to those of other known phytoestrogens. Together, these findings broaden our understanding of the structure-activity relationships for nonsteroidal estrogens and present a series of new chemical prototypes for the future development of potentially useful agonists and antagonists for this nuclear receptor. The wide distribution of weakly estrogenic flavonoid pigments in food crops and medicinal plants raises additional questions about the possible health risks and benefits of these compounds, meriting closer examination of their presence in the human diet. PMID- 8341278 TI - Altered cisplatin and cadmium resistance and cell survival in Chinese hamster ovary cells expressing mouse metallothionein. AB - Metallothionein (MT) proteins are associated with resistance to the toxic effects of heavy metals, chemotherapeutic drugs, and alkylating agents. It has been suggested that MT may mediate both resistance to toxic agents and cellular metal homeostasis. To study the role of MT, we obtained cells expressing a range of MT levels in the absence of heavy metal induction. We cotransfected the eukaryotic G418 resistance vector pSV2neo and mouse MT-1 cDNA in a pBR322 vector into Chinese hamster ovary cells. Of 200 transfected clonal cell populations, five had constitutive MT expression ranging from 31 to 87 ng of MT/mg of protein. All five populations had increased resistance to cadmium but were less resistant to cisplatin than control cells. On the other hand, the level of foreign MT expression correlated well with the degree of cisplatin resistance among the five clones. Resistance to ionizing radiation and growth rate in the absence of drug or radiation treatment were not affected. However, transfected MT gene expression inhibited the ability of Chinese hamster ovary cells to form colonies in the absence of toxic drug treatment (r = -0.95). The perturbation of cisplatin sensitivity after genetic alteration of MT expression indicates a role for MT in drug resistance: however, the fact that transfected MT gene expression decreased rather than increased drug resistance and decreased plating efficiency in the absence of drug implies that the role of MT may not be one of simply "scavenging" toxic molecules. These data suggest a role for MT in homeostatic cellular processes that, when distributed by transfection of active MT genes, have an effect on cellular drug resistance. PMID- 8341279 TI - Postnatal changes in the expression and distribution of pulmonary cytochrome P450 monooxygenases during Clara cell differentiation in rabbits. AB - Previous studies have indicated that both cytodifferentiation of Clara cells and the onset of pulmonary cytochrome P450 activity are postnatal events. However, the relationship between these two events during lung development remains poorly understood. To determine how these events interrelate, we examined rabbit Clara cells during postnatal differentiation, with the following goals in mind: 1) to identify the patterns of intracellular expression of cytochrome P450 monooxygenase isozymes 2B and 4B and cytochrome P450 reductase, 2) to describe the biogenesis of the organelles with which these isozymes are associated, namely smooth and rough endoplasmic reticulum, and 3) to compare the patterns of expression with cytochrome P450 activity in the whole lung over the same period. Lungs of rabbits ranging in age from 24 days gestational age (DGA) to 25 weeks postnatally were studied. Ultrastructural morphometry showed that smooth endoplasmic reticulum averaged < 5% of the Clara cell volume in late gestational (24-30 DGA) and neonatal rabbits [0-7 days postnatally (DPN)], grew to 20-30% of the cell volume in 14-21-DPN animals, and approximated adult levels (> 40%) in 28 DPN rabbits. In contrast, rough endoplasmic reticulum decreased from > 10% of the cell volume at 27 DGA to < 5% in adults. All postnatal animals showed considerable heterogeneity in the abundance of smooth endoplasmic reticulum among individual cells. Immunohistochemistry revealed that cytochrome P450 reductase appeared in Clara cells earlier (28 DGA) than did either isozyme 2B or 4B (1 DPN). Each antigen was detected first in the apical borders of the cells, then throughout the cytoplasm in a few cells by 7 DPN, and finally in adult abundance by 28 DPN. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting showed that cytochrome P450 protein concentrations increased postnatally. Cytochrome P450 heme protein was not detected spectrophotometrically in the lungs of animals younger than 3 DPN but increased to approximately 70% of adult levels by 28 DPN. Likewise, cytochrome P450 activity (measured as ethoxy- and pentoxyresorufin O-dealkylation) was not detected in animals younger than 2 DPN but increased to approximately 75% of adult levels by 28 DPN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8341280 TI - Associated complement C3b. Towards an understanding of its intracellular modifications. AB - Covalent Superose microspheres-bound C3b was used as a model system to simplify the analysis of antigen-bound C3b modifications during antigen processing. The model was set up using purified C3 and Superose-bound trypsin. C3b was covalently bound to Superose through an ester link, as indicated by lability to hydroxylamine treatment at alkaline pH. C3b-Superose was incubated with L subcellular fraction, enriched in endosomes/lysosomes, purified from U937 cell line. Two types of limited activities on the C3b-Superose model system were detected: (i) a proteolytic activity cleaving C3b into mainly a C3c-like fragment which was released and a C3d-like fragment of apparent M(r) 32 kDa which remained bound to Superose through the original ester link; (ii) an esterolytic activity cleaving the ester bond and releasing C3b. Inhibition experiments pointed to the involvement of serine, aspartyl and cysteine proteases. Cathepsin B appeared most probably as one of the major proteases of L fraction catalysing the proteolysis of the C3b-bound. Kinetic studies were in favour of a good stability on the ester bond, supporting an effective role of C3b as a chaperone during the extracellular and intracellular travel of C3b-bound antigen. PMID- 8341281 TI - Development and functional characterization of a murine/human chimeric antibody with specificity for the human interleukin-2 receptor. AB - A murine/human chimeric antibody, with specificity for the human interleukin-2 receptor, was developed by genetic engineering. For this purpose, the light and heavy chain variable region exons encoding the murine monoclonal antibody 2C8 were isolated and inserted into expression vectors containing the human kappa and gamma-1 constant regions. After transfection by electroporation of the chimeric genes into murine Sp 2/0 hybridoma cells, transfectomas secreting the complete chimeric antibody were selected. The chimeric antibody has similar binding properties as the original murine antibody. The in vitro cytotoxic effects of the murine and the chimeric antibodies were compared. PMID- 8341282 TI - An alternative method for T-cell receptor repertoire analysis: clustering of human V-beta subfamilies selected in responses to staphylococcal enterotoxins B and E. AB - We have designed a convenient procedure for the analysis of V beta repertoire expression in polyclonal T-cell populations. In this procedure T-cell RNA is converted to cDNA, polydC-tailed with terminal deoxynucleotidyl transferase and submitted to one-side specificity PCR amplification with a constant region oligonucleotide primer. The amplified material is then analysed by reverse spot test hybridization: after 32P-labelling, the amplification product is put to hybridize on a membrane where specially designed V beta subfamily-specific probes are immobilized. The radioactivity fixed on each probe can then be easily quantified and the signal obtained is directly proportional to the initial amount of homologous RNA. We applied this technique to the study of V beta gene selection following T-cell stimulation by staphylococcal enterotoxins B and E. We show that with these toxins two almost non-overlapping sets of T-cells are recruited and that this selection is likely to be dependent on specific amino acid residues shaping the fourth complementarity determining region of the TCR beta chain. These residues constitute two tandemly-conserved tripeptide sequences (Asp39Pro40Gly41)-(Val69Ser70Arg71) and (Arg66Phe67Ser68)-(Asp88Ser89Ala90) in the SEB- and the SEE-responsive V beta gene clusters respectively. PMID- 8341284 TI - Proteins separated from human IgG molecules. AB - Immunoglobulin G binding proteins were separated from human IgG molecules using 1 N acetic acid followed by 5 M guanidinium chloride in 0.1 M acetic acid. The proteins thus obtained were heterogeneous as demonstrated by SDS-PAGE and reverse phase HPLC. The isolated proteins consisted of two types: the C3a and C4a complement fragments (anaphylatoxins) and immunoglobulin peptide chain fragments V kappa I and C gamma 3. Both anaphylatoxins immobilized on cellulose nitrate membranes could reassociate with intact IgG molecules. The ubiquitous presence of C3a in IgG preparations was demonstrated using monoclonal antibodies specific for C3a. Nearly all of the bound anaphylatoxin molecules were found in the Fab fragment. These findings suggest that IgG molecules can eliminate anaphylatoxins from the circulation, and thus prevent harmful effects due to these active complement components. PMID- 8341283 TI - Tumor-induced modulation of macrophage class II MHC molecule mRNA expression. AB - Class II MHC protein expression in macrophages (M phi) is reduced during tumor growth. Because regulation of class II MHC proteins occurs during transcription, tumor growth may suppress class II MHC protein expression by suppressing mRNA. The decrease in class II mRNA may result from (i) a decrease in M phi responsiveness to an inducing agent, such as interferon-gamma (IFN-gamma), or (ii) an increase in M phi sensitivity to suppressing agents, such as prostaglandin E2 (PGE2). To determine how tumors induce suppression of class II mRNA, M phi were cultured in the presence of IFN-gamma with or without other factors, and Northern blot analyses were performed. Unstimulated normal host (NH) or tumor-bearing host (TBH) M phi do not express detectable class II mRNA. The addition of IFN-gamma induces class II mRNA expression in NH and TBH M phi, but class II mRNA expression is significantly lower in TBH M phi. Kinetic studies suggested that NH M phi class II mRNA is induced faster and in greater amounts than TBH M phi class II mRNA. There is a decrease in M phi class II mRNA stability during tumor growth that may account for the decreased induction by IFN gamma. Lipopolysaccharide (LPS) suppresses class II mRNA induction in both NH and TBH IFN-gamma-treated M phi, but TBH M phi are more sensitive to its suppression. PGE2 and tumor-necrosis factor-alpha (TNF-alpha), two factors produced by LPS stimulated M phi, were tested for their ability to modulate class II mRNA expression in NH and TBH IFN-gamma-treated M phi. PGE2 suppressed class II mRNA expression in both NH and TBH M phi. The addition of TNF-alpha to IFN-gamma treated M phi suppressed class II mRNA in NH M phi but, surprisingly, had an additive effect on IFN-gamma-induced class II mRNA expression. TNF-alpha did not induce class II mRNA expression in TBH M phi in the absence of IFN-gamma. The cause of the reduced class II mRNA expression during tumor growth is a decreased response to IFN-gamma and an increased sensitivity to PGE2. This change may cause the observed suppression mediated by TBH M phi. PMID- 8341285 TI - Cellular recognition and HLA restriction of a midsequence HBsAg peptide in hepatitis B vaccinated individuals. AB - Vaccination with native HBsAg results in both a humoral and a cellular immune response in humans. In individuals who responded to vaccination, the HBsAg (S region) specific response, as measured by cell proliferation, diminished significantly after 12 weeks, a time when the antibody response was still vigorous. Reduced and nonreduced HBsAg were equivalent in eliciting lymphocyte proliferation. Anti-MHC class II monoclonal antibodies were used in blocking studies to demonstrate that anti-HLA-DR but not anti-HLA-DQ or anti-HLA-DP inhibited specific lymphocyte proliferation to HBsAg. Both the monomer (reduced) and dimer (nonreduced) forms of an immunodominant midsequence HBsAg peptide (amino acid residues 139-146) produced lymphocyte proliferation roughly comparable to that induced by whole HBsAg in 6 of 7 responders immunized with whole HBsAg and the peptide-induced proliferation was blocked by anti-HLA-DR but not by anti-HLA-DP antibodies. These results suggest that HBsAg p 139-146 is a major immunodominant peptide of HBsAg and is restricted by HLA-DR. PMID- 8341286 TI - Significance and properties of the autoanti-metatype immune response. PMID- 8341287 TI - An anti-lipid A antibody obtained from the human fetal repertoire is encoded by VH6-V lambda 1 genes. AB - The human hybridoma cell line CB-201 has been obtained from a fusion of fetal spleen lymphocytes (31st gestational week) with heteromyeloma cells. The IgM (lambda) secreted was found to bind to lipid A, whereas other endogenous and exogenous antigens were not recognized. The CB-201 antibody is encoded by the unmutated VH6 gene recombined with DN4 and JH3 elements and a V lambda subgroup 1 gene. Therefore, a VH gene, which was previously described to be over-represented in the fetal repertoire and to be expressed in autoantibody-producing B cells, may encode an anti-bacterial specificity. PMID- 8341288 TI - Affinity of monoclonal antibodies to large multivalent antigens: influence of steric hindrance on antibody affinity constants calculated from Scatchard plots. PMID- 8341289 TI - Early combination therapy with bromocriptine and levodopa in Parkinson's disease. AB - The use of early combination therapy with bromocriptine (Br) and levodopa (LD) in Parkinson's disease is controversial. It has been suggested that treatment with this regimen would prevent or delay the onset of motor fluctuations and dyskinesia. Thus, some have recommended it as a standard of care. This recommendation is based on the theory that LD may accelerate the progression of PD and clinical experience using Br monotherapy in early Parkinson's disease, which suggested that Br causes fewer late complications. This article reviews these arguments and shows that the theories are unproven. A single, uncontrolled trial is often referred to as evidence for efficacy of early combination therapy. We critically review this and five other studies which have evaluated the treatment strategy. We show that the literature is often misleading and that these trials do not support the efficacy of early combination therapy. We conclude that there is no justifiable reason to use a combination of Br and LD in early parkinsonian patients. PMID- 8341290 TI - The detection of preclinical Parkinson's disease: what is the role of positron emission tomography? AB - On clinical criteria alone, the diagnosis of early Parkinson's disease can be difficult and, by definition, the prospective recognition of preclinical Parkinson's disease is impossible. Positron emission tomography (PET) using [18F]dopa as tracer has been proposed as a means of identifying patients with preclinical disease. The number of subjects detected to date has been few; most have been identified by serendipity or during the course of family studies. This review examines the significance of a single abnormal scan in an apparently healthy subject in terms of the relationship between normal and abnormal values and the time course of the disease. PMID- 8341291 TI - Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine rich human neuroblastoma cell line. AB - Levodopa, at concentrations of 0.25 x 10(-4) M or larger, is toxic for the human neuroblastoma cell NB69. Toxicity is associated with high levels of quinones, increased activity of complex II-III, and lack of changes of complex I of the mitochondrial respiratory chain. Deprenyl, which does not alter the production of quinones, has a partial protective effect. Tocopherol, 23 or 115 x 10(-6) M, lacks significant preventive effect on levodopa toxicity, but ascorbic acid, 10( 3) M, prevents levodopa toxicity and quinone formation. Deprenyl, 10(-4) M, provides additional protection in cultures treated with levodopa and ascorbic acid. Our results indicate that ascorbic acid and deprenyl prevent levodopa neurotoxicity by unrelated mechanisms. Both compounds should be considered as complementary drugs to test for slowing the progression of Parkinson's disease. PMID- 8341292 TI - The syndrome of gait ignition failure: a report of six cases. AB - The syndrome of gait ignition failure is described in six patients in whom difficulty initiating walking was the major symptom. The gait had elements of parkinsonism with start and turn hesitation, shuffling, and freezing. Unlike parkinsonism, however, the gait was relatively normal once entrained; the posture was upright, and good arm swing, a normal stride length, and no festination were seen. Equilibrium was normal or near normal, and when seated or lying, rhythmic leg movements were generated normally. Facial expression, upper limb mobility, and whole body movements were well-preserved. This gait disorder differed from that seen in Parkinson's disease and the so-called "frontal" or "senile" disorders of gait and gait "apraxia." The causes of this gait syndrome are not clear but it may be due to frontal lobe vascular disease and/or focal degeneration of the frontal lobes. PMID- 8341293 TI - Primary progressive freezing gait. AB - Freezing gait is an incapacitating symptom often observed in patients with Parkinson's disease. It has been less frequently described in association with multi-infarct state, multisystem atrophies, and normotensive hydrocephalus. In our movement disorder clinic, we have diagnosed (and followed up to 3 years; median, 16 months), 18 patients in whom progressive freezing gait was the sole neurological dysfunction. These 15 men and 3 women (aged 60-82 years; 74 +/- 6) were subjected to an extensive neurological workup that included clinical evaluation, videotaping for grading of gait disability, comprehensive blood and cerebrospinal fluid (CSF) analysis, and brain computed tomography (CT) and magnetic resonance imaging (MRI). Mean disease duration was 2.5 +/- 1.9 years (range, 0.5-6). Neurological examination disclosed freezing gait, often associated with varying degrees of postural instability. The degree of freezing gait ranged from sudden motor blocks only when confronted with obstacles to severe disability with total inability to start walking requiring a walker, massive assistance, or a wheelchair. However, patients could mimic gait movements with absolutely no freezing when seated or lying prone, and most of them could overcome arrests by the "walking-over-lines" maneuver. Otherwise, neurological examination was normal with no signs of bradykinesia, rigidity, or tremor. Blood chemistry and CSF analysis were normal. Brain CT and MRI were normal or showed mild cortical atrophy in 12 and putative lacunes in 6 patients. Therapy with levodopa or dopamine agonists was ineffective. During the follow-up period, a gradual progression of the freezing gait was observed. However, it remained unaccompanied by any other neurological findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341294 TI - Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa. AB - L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltransferase (COMT). This reduces the amount of L-dopa available for entry into brain. We studied the effect of OR-611, a new COMT inhibitor, on plasma and brain 6-[18F] fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (3OMFD). PET measurements of striatal 6FD concentrations showed an average 2.3-fold increase following OR-611 pretreatment, compared to the same animals in the control state. OR-611 inhibits plasma metabolism of 6FD and increases brain uptake of this L-dopa analog. OR-611 appears to be a promising agent as an adjunct to L-dopa for the treatment of patients with Parkinson's disease. PMID- 8341295 TI - Lewy bodies in the lateral hypothalamus: do they imply neuronal loss? AB - Lewy bodies have been found in the hypothalamic lateral tuberal nucleus (NTL) and the adjoining tuberomammillary nucleus (TM) in Parkinson's disease (PD). The NTL is severely atrophic in Huntington's disease; the TM seems unaffected. In this study, we examined the NTL and the TM of seven PD patients and one patient with presumed PD to assess whether the presence of Lewy bodies indicated neuronal loss. Most Lewy bodies were found in the TM, but they were also present in the NTL of seven of the eight patients. The number of NTL neurons in the PD patients was similar to a group of 14 nonneurological controls, seven Alzheimer's disease (AD) patients, and two AIDS patients with dementia. This challenges the hypothesis that Lewy bodies are a sign of significant cell death. The TM, whose cells could not be counted, did not seem depleted in neuronal numbers, although occasional neuronophagia was observed. PMID- 8341296 TI - Axial motor disturbances after hypoxic lesions of the globus pallidus. AB - Four subjects aged between 29 and 60 years were examined because of axial motor impairment after hypoxic brain injury. Magnetic resonance imaging revealed circumscribed lesions of the globus pallidus in every case. The association of freezing of the gait, speech disorders, axial bradykinesia, and postural disturbances, with no rigidity or tremor and little or no distal akinesia, suggests a role of the globus pallidus in controlling axial motion. PMID- 8341297 TI - Laterality of onset in idiopathic torsion dystonia. AB - Idiopathic torsion dystonia (ITD) is a dominantly inherited disorder with incomplete penetrance. It is important to identify factors that may cause dystonia or prevent its occurrence in a genetically predisposed individual. Because dystonia may be precipitated by peripheral triggers, we have investigated whether the preferential use of a limb affects the development of dystonia. Analysis of the correlation between the side of motor dominance and the limbs in which dystonic symptoms first appeared was performed in 49 patients with ITD ascertained in a country-wide survey in Israel. The dominant motor side was determined in 45 cases (92%). Among 29 patients with lateralized limb onset, 24 showed right-side motor dominance, of whom 21 had dystonia onset in a right limb. The first sign was in a left limb for all five cases with left-side motor dominance (90% coincidence). The pattern of limb involvement was studied. Detection bias could be ruled out. The highly significant relationship between the motor dominance and the laterality of limb onset in ITD patients suggests that the preferred use of a limb may trigger the onset of dystonia. PMID- 8341298 TI - Geniospasm: hereditary chin trembling. AB - Geniospasm is a hereditary disorder characterized by episodic, usually stress induced involuntary trembling of the chin. Nineteen families from Europe and the U.S.A. suffering from this disorder have been described since 1894. We present three cases from two newly detected families. There was no evidence of any other nervous system abnormality, although abnormal EEG, sleep disorders, and involvement of other facial muscles have been described in rare cases. Geniospasm is transmitted as an autosomal-dominant trait with high penetrance. It must be differentiated from facial myokymia, palatal tremor, and essential tremor affecting facial muscles. Neurophysiological and molecular mechanisms of this peculiar disorder are unknown. PMID- 8341299 TI - Cisapride treatment of constipation in Parkinson's disease. AB - Constipation, a frequent symptom in Parkinson's disease (PD), is probably caused by degeneration of the autonomic nervous system, particularly the myenteric plexus. Cisapride is a drug that causes increased release of acetylcholine in the myenteric plexus. In a pilot study, cisapride therapy was investigated in 20 PD patients, 10 women and 10 men, who suffered from delayed intestinal transit. In all cases, cisapride therapy was associated with a significant acceleration of colonic transit, as measured by radioopaque pellets viewed on radiographs. Pellet count fell from a mean of 53.8 pretreatment to 30.4 after cisapride treatment. No adverse reaction and no "overshoot affects," such as diarrhea, were seen. Our findings suggest that cisapride may alleviate the constipation associated with Parkinson's disease. PMID- 8341300 TI - Modulatory effect of clozapine on levodopa response in Parkinson's disease: a preliminary study. AB - Clozapine has been shown not only to be effective in ameliorating dopaminomimetic psychosis but to improve parkinsonian symptomatology. Six parkinsonian patients with motor fluctuations under levodopa treatment and severe interdose "off" periods (believed to be mediated by an inhibitory effect of subthreshold levels of levodopa) underwent a trial of clozapine. The effects of this drug on levodopa response were measured by means of an acute levodopa test both before and after receiving clozapine. After 1 month of treatment, clozapine 25 mg/day reduced parkinsonian scores at all stages of the evaluation (pre-levodopa "off," "on," and interdose "off"). The effect was consistently more significant for the interdose "off." Clozapine could be exerting its beneficial effects through the inhibition of an inhibitory effect mediated by low-level dopaminergic stimulation, thus behaving as an apparent anti-parkinsonian drug. PMID- 8341301 TI - Reversible striatal hypermetabolism in a case of Sydenham's chorea. AB - We studied a 10-year-old girl with Sydenham's chorea (SC) using positron emission tomography (PET) with fluorodeoxyglucose (FDG). Choreic movements involved the head and the left side of her body. PET showed increased glucose metabolism in the right caudate nucleus and putamen. Three months after complete recovery, striatal glucose metabolism had returned to normal in the caudate nucleus. In the right putamen, glucose metabolism had decreased compared to that in the first study but remained elevated compared to that of normal young adults. We propose that the transient striatal hypermetabolism may have been due to increased afferent inputs to the striatum as a consequence of striatal or subthalamic nucleus dysfunction. PMID- 8341302 TI - Inverse masticatory muscle activity due to syringobulbia. AB - The clinical, radiological, and electrophysiological data of a 25-year-old woman with "inverse masticatory muscle activity" due to syringobulbia is presented. This uncommon brain stem syndrome may be due to a disturbance in central programming of mastication. PMID- 8341303 TI - Orofacial dystonia and rest tremor in a patient with normal brain pathology. AB - We report a patient with cranial dystonia who also had rest tremor of one arm and who developed drug-induced parkinsonism on treatment. The patient's brain was normal on autopsy. We also review the findings in the few reported cases of cranial dystonia with pathology. PMID- 8341304 TI - Cerebellar ataxia in ataxic hemiparesis? A kinematic and EMG analysis. AB - It has recently been proposed that the ataxia in ataxic hemiparesis is a clumsiness common to all patients with hemiparesis and not indicative of any involvement of corticopontocerebellar or cerebellocortical pathways. In disagreement with this view, we report here that a patient with ataxic hemiparesis, following a lesion of the corona radiata, showed the disorders in kinematic and electromyographic (EMG) parameters of goal-directed movements that have recently been demonstrated to be characteristic of patients with cerebellar lesions. This suggests involvement of corticopontocerebellar or cerebellocortical pathways in ataxic hemiparesis. PMID- 8341305 TI - Significant improvement of stiff-person syndrome after paraspinal injection of botulinum toxin A. AB - Following several months of low back pain, a 36-year-old man developed progressive stiffness of the abdominal, low back, and thigh muscles. On examination, these muscles demonstrated marked hypertonia consistent with the clinical diagnosis of stiff-person syndrome. The patient demonstrated increased lumbar lordosis and had focal hyperhidrosis at different sites. Electromyography showed continuous activity of the paraspinal and thigh muscles, and serum and cerebrospinal fluid antibodies to glutamic acid decarboxylase (GAD) were markedly elevated. Diazepam and Lioresal offered partial pain relief. Paraspinal muscle administration of botulinum toxin A reduced the tone of paraspinal and thigh muscles significantly and resulted in marked improvement of ambulation and cessation of pain. PMID- 8341306 TI - Linkage analysis with chromosome 9 markers in hereditary essential tremor. AB - Hereditary essential tremor (ET) is an autosomal dominant disorder with variable expression and reduced penetrance. A tremor indistinguishable from ET may be observed in patients with autosomal dominant idiopathic torsion dystonia (ITD), in which the disease locus has been mapped to 9q32-34 in some kindreds, tightly linked to the argininosuccinate synthetase (ASS) locus. We performed linkage analysis in 15 families with ET containing 60 definitely affected individuals, using dinucleotide repeat polymorphisms at the ASS locus and the Abelson locus (ABL). Cumulative lod scores were -19.5 for ASS and -10.8 for ABL at a recombination fraction of 0.01, and tight linkage to ASS was excluded individually in 11 of the families. These data indicate that the ET gene is not allelic to that causing ITD. PMID- 8341307 TI - Painless legs and moving toes: a syndrome related to painful legs and moving toes? AB - The syndrome of painful legs and moving toes consists of continuous or semicontinuous involuntary writhing movements of the toes associated with pain in the affected extremity. We report a 57-year-old man with a 33-year history of painless and semicontinuous involuntary movements of the toes of the left foot similar to those seen in painful legs and moving toes. There was no family history of movement disorder. The history and physical examination were negative for significant trauma, radiculopathy, or peripheral neuropathy. There were no other neurological findings or involuntary movements. It is unlikely that the involuntary movements were precipitated by neuroleptics or psychosis. CT scan of the head; EEG, CT, and MRI scans of the lumbosacral spine; and EMG and nerve conduction studies of the legs showed no significant abnormalities except for a predominant cocontraction of the left foot flexors and extensors at 0.6-1.2 Hz in a pattern sometimes seen in painful legs and moving toes. We conclude that there is a condition clinically and electrophysiologically similar to painful legs and moving toes that we call painless legs and moving toes, the etiology of which remains undetermined. PMID- 8341308 TI - Interactive video conferencing: a means of providing interim care to Parkinson's disease patients. AB - Inequity in health care delivery is attributable to a variety of factors including geographic isolation. Patients living far from major urban centers have limited access to medical specialists. In the instance of Parkinson's disease (PD), optimal assessment and care may depend upon availability of specialty health care providers. In order to broaden health care access, interactive video conference (IVC) units are being developed for medical use. IVC allows a patient at a distant site to be "seen and heard" by a hospital-based physician; simultaneously, the patient can "see and hear" the doctor. To establish the validity of this technology in the evaluation of PD, nine patients were independently examined and scored (UPDRS) by two movement disorder specialists. One examination was performed in-person by the usual physician. The other examination was performed on the same day via IVC over a distance of 350 miles by an examiner previously unfamiliar with the patients. Individual patient scores did not differ based on examiner (Spearman Rho Correlation Coefficients: UPDRS total scores r = 0.933, p < 0.0002; Hoehn and Yahr Scale r = 0.883, p < 0.001). A standardized exit interview was conducted to assess patients' perceptions of this application of video technology. Responses were favorable and virtually all patients viewed this as a means of accessing better health care. We conclude that valid motor assessments of PD patients can be made via IVC. PMID- 8341309 TI - Hemidystonia symptomatic of primary antiphospholipid syndrome in childhood. AB - We report three children with hemidystonia in whom anti-cardiolipin (aCL) antibodies were demonstrated. Systemic lupus erythematosus was excluded on the basis of both clinical and serological criteria, and the diagnosis of primary antiphospholipid syndrome (PAPS) was made. In two cases, aCL antibodies could be causally related to a presumed immune-mediated thrombotic event involving the basal ganglia as shown by magnetic resonance imaging (MRI). In the remaining patient the finding of white matter alteration on NMR might be due to cross reactivity of anti-phospholipid (aPL) antibodies with cerebral phospholipids, resulting in demyelination. We suggest that PAPS must always be considered when isolated or recurrent focal cerebral ischaemia, and particularly hemidystonia, occur in childhood. PMID- 8341310 TI - Neuropathology of lubag (x-linked dystonia parkinsonism). AB - Lubag is an x-linked recessive dystonia parkinsonism that affects Filipino men originating principally from the Panay Island. Linkage analysis has confirmed the mode of inheritance and localized the disease gene to the proximal long arm of the x-chromosome. We studied the brain of a 34 year old Filipino man affected with lubag. He developed truncal dystonia at age 30, which subsequently generalized. With disease progression, he also presented with parkinsonism including, rigidity, bradykinesia, and impaired balance. His symptoms were largely unaffected by medication and, at age 34, he underwent a right cryothalamotomy. He died suddenly 2 days after the procedure. The principal neuropathological findings were neuronal loss and a multifocal mosaic pattern of astrocytosis restricted to the caudate and lateral putamen. Similar findings have been reported in two other men with dystonia--one Filipino and the other non Filipino. The similar pathology of the two Filipino men suggests that this is the pathology of lubag. Recognition of this pathology in a non-Filipino man suggests that the mutation causing lubag may not be restricted to the Filipino population. PMID- 8341311 TI - Brain glucose metabolism and dopamine D2 receptor analysis in a patient with hemiparkinsonism-hemiatrophy syndrome. AB - We report findings on brain glucose metabolism and dopamine D2 receptors generated by positron emission tomography (PET) in a 67-year-old woman with right hemiparkinsonism-hemiatrophy syndrome (HP-HA). PET with [18F]-fluorodeoxyglucose (FDG) showed marked glucose metabolism asymmetry. There were significant reductions in glucose uptake at the level of the basal ganglia and, to lesser extent, in the fronto-parietal cortex contralateral to the clinically involved side. These changes were different from those found in a patient with hemi Parkinson's disease who was scanned under similar conditions. Because the patient with HP-HA had only minimal response to levodopa therapy, we evaluated post synaptic dopaminergic structures using PET with [18F]-fluoroethylspiperone (FESP). No striatal binding asymmetry was found in FESP/PET, which suggests a sparing of striatal dopamine D2 receptors. The changes in FDG uptake which we found were in brain areas relevant to the clinical features of HP-HA syndrome. In addition, our study provides evidence that FDG/PET may help to differentiate HP HA syndrome from hemi-Parkinson's disease. In most instances, since HP-HA is associated with a more benign clinical course than Parkinson's disease, this distinction is of clinical important. PMID- 8341312 TI - Developmental stuttering followed by intermittent jaw opening dystonia. PMID- 8341313 TI - Leg tremor mimicking orthostatic tremor as an initial manifestation of Parkinson's disease. PMID- 8341314 TI - Levodopa-responsive parkinsonism associated with basal ganglia calcification and primary hypoparathyroidism. PMID- 8341315 TI - Involuntary humming in autopsy-proven Parkinson's disease. PMID- 8341316 TI - Benign hereditary chorea or hereditary idiopathic dystonia? PMID- 8341317 TI - Cloning and characterisation of cDNA clones encoding two Babesia bovis proteins with homologous amino- and carboxy-terminal domains. AB - A dextran sulphate protein (DSP) fraction derived from Babesia bovis has previously been shown to induce a protective immune response in cattle. A B. bovis cDNA library was screened with both the complete anti-DSP serum and a subfraction of the anti-DSP serum affinity purified on a native B. bovis protein of approx. 80 kDa. cDNA clones encoding two different B. bovis proteins were identified. The product of one gene, Bv80, has a single divergent copy of a sequence of 149 amino acids (approx. 30% amino acid identity) in both the amino- and carboxy-terminal domains. These domains are separated by an array of short variant repeat sequences rich in proline and glutamic acid. The product of the other gene, BvVAl (homologous to the previously described 225-kDa B. bovis protein)[19], is predicted to have a single divergent copy of a sequence of 170 171 amino acids (approx. 35% amino acid identity) in both the amino- and carboxy terminal domains. These domains are also separated by an array of repeats. The 73 amino acid repeat unit of this array is composed of a number of variant derivatives of shorter repeat units. Detailed analysis of genomic clones flanking two alleles of the gene encoding BvVAl/225 kDa identified further members of a multi-gene family. This region of the genome of B. bovis has been subject to a large number of amplification processes. PMID- 8341318 TI - A mitochondrial heat shock protein from Crithidia fasciculata. AB - MCP72 is a mitochondrial hsp70 protein from the trypanosomatid Crithidia fasciculata. An MCP72 cDNA clone was isolated from a C. fasciculata cDNA library by screening with antiserum specific for the homologous protein of Trypanosoma cruzi [9]. The MCP72 cDNA encodes a polypeptide of 663 amino acids which is 84% identical to the Trypanosoma cruzi protein and 56% identical to the Escherichia coli hsp70 protein DnaK. MCP72 is less similar to other hsp70 proteins. Native MCP72 was purified to homogeneity by ATP-agarose affinity chromatography. Comparison of its N-terminal amino acid sequence with that deduced from the cDNA sequence shows that 20 amino acid residues had been cleaved from the N-terminus; this sequence probably represents a mitochondrial import signal which is cleaved during translocation into the mitochondrion. Fluorescence microscopy, using antibodies specific for MCP72, indicates that the protein is concentrated in a region of the mitochondrial matrix which surrounds the kinetoplast. PMID- 8341319 TI - Synthesis and activity of inhibitors highly specific for the glycolytic enzymes from Trypanosoma brucei. AB - Most glycosomal enzymes of Trypanosoma brucei carry a relatively high number of positive charges. In at least 3 of the enzymes some of the charges unique to these enzymes are concentrated in 2 distinct areas on the enzymes' surface, about 4 nm apart [4] and these positively charged structural elements have been suggested to be the site of interaction with the trypanocidal drug Suramin. We have synthesized a series of symmetrical long chain molecules with negative charges or strong dipoles at each end. Several of these compounds inhibited the glycosomal enzymes more strongly than Suramin. They also exhibited a specificity for the trypanosome enzymes, when compared with homologous enzymes from other organisms. By varying the chain length of the active compounds, a 4-nm distance between the molecules' extremes proved optimal for inhibition. Tetra-substituted compounds were better than di-substituted. Modifications introduced at the two ends indicated that a planar orientation, with an amide bond linking a phenyl ring to the chain, is preferred. Inhibition kinetics for some of the enzymes indicated the existence of multi-site interactions with the inhibitors. PMID- 8341320 TI - Genetic variability and evolution of the Schistosoma genome analysed by using random amplified polymorphic DNA markers. AB - The usefulness of random amplified polymorphic DNA markers (RAPD) was assayed in an attempt to discriminate among species, strains and individuals within the genus Schistosoma. Depending on the species, 40-50 arbitrary decamer oligonucleotides were used as primers to amplify total DNA by the polymerase chain reaction (PCR). An important polymorphism was observed among 5 species, allowing a phylogenetic tree to be outlined. These differences can be used for rapid and accurate identification. A limited but easily detectable polymorphism was revealed among 3 strains of a single species (Schistosoma mansoni). Minor differences were observed among individuals of a single strain. A RAPD marker allows sexual discrimination between individuals from the terminal spined-egg species group. Although a limited number of strains have been examined, the results already indicate clearly that RAPD markers constitute a powerful tool for the analysis of genetic variability. This new tool will considerably extend the information available from morphology, isozyme and limited restriction fragment length polymorphism data and opens the way to genetic analysis of these species. PMID- 8341321 TI - Molecular cloning and localization of an abundant novel protein of Plasmodium berghei. AB - Screening of Plasmodium berghei genomic libraries using DNA insert corresponding to the 3' half of P. falciparum 70-kDa heat shock protein gene identified several abundant clones which represent a novel gene in the parasite. The complete sequence was obtained using an approach based on inverse polymerase chain reaction. Analysis of the deduced amino acid sequence revealed the presence of 19 imperfect repeats of the sequence Gly-Gly-Met-Pro toward the carboxy terminus. Except for the similar sequence repeated seven times in the malarial 70-kDa heat shock protein, the sequence of the cloned gene product is very different. Moreover, the sequence also revealed acidic and basic domains in the protein which are more than 60% similar in sequence to functional domains present in numerous DNA binding transcription factors. A 56-kDa protein was identified by immunoprecipitation from labeled P. berghei extract using antisera raised in mice against gene products expressed in Escherichia coli. The protein is present in all the different life cycle stages of the parasites as revealed by immunoelectron microscopy. PMID- 8341322 TI - Characterization of the Schistosoma mansoni gene encoding the glycolytic enzyme, triosephosphate isomerase. AB - The complete gene encoding Schistosoma mansoni triosephosphate isomerase (TPI) was isolated from a lambda phage genomic library on 2 overlapping clones. These genomic clones have been characterized by restriction mapping and DNA sequencing of the 5' flanking region, the exons, the intron boundaries and the polyadenylation addition site. S. mansoni TPI is encoded by 6 exons spanning a region of about 12 kb. The 5 introns are located at positions precisely analogous to those of mammalian TPI genes but one of the 6 mammalian TPI introns is missing in S. mansoni. We find no evidence of spliced leader involvement in TPI gene expression. The gene is preceded by at least 4 tandem copies of a 2.5-kb repetitive sequence. While the 12-kb size for the S. mansoni TPI gene is much larger than the 3-4 kb typical of mammalian TPI genes, the 42-bp first intron is unusually short. The transcription initiation site for the S. mansoni TPI gene is heterogeneous. Genomic Southern blot analysis suggests that TPI is expressed from a single copy gene. PMID- 8341323 TI - Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans sialidase on the trypanosome. AB - Trypanosoma cruzi attaches and invades a large variety of mammalian cells. The nature of the cell receptors and of the corresponding parasite counter-receptors that mediate T. cruzi-host cell interaction are not known. Three sialic acid deficient mutants of Chinese hamster ovary (CHO) cells were used to probe the role of host sialyl residues in T. cruzi infection. All three mutants supported adhesion and infection to a much lower extent than the parental CHO cells. One of the mutants, Lec2, contains sugar chains terminating in non-reducing beta Gal residues, which are acceptors for sialylation by the T. cruzi trans-sialidase. Re sialylation of Lec2 cells restored T. cruzi adhesion and invasion to about the same extent as wild-type cells. Digestion of wild-type cells with bacterial sialidase reduced T. cruzi interaction but after re-sialylation, the cells were almost as good as control, naturally sialylated parental cells. These results suggest that T. cruzi recognizes sialyl residues on the surface of host cells during invasion. On the other hand, affinity-purified trans-sialidase blocked T. cruzi adherence and invasion of sialylated cells, and had no effect on parasite interaction with sialic acid-deficient Lec2 mutant. Furthermore, 2,3 sialyllactose, a substrate for the trans-sialidase, competitively inhibited T. cruzi invasion of sialylated parental K1 cells, but 2,6-sialyllactose, which does not react with the trans-sialidase, was without effect, as were other sugars that do not contain alpha 2,3 sialyl residues. These results suggest that the trans sialidase functions as a counter-receptor for trypomastigote binding to alpha 2,3 sialyl receptors on host cells as a prelude to T. cruzi invasion. PMID- 8341324 TI - Structure and expression of a post-transcriptionally regulated malaria gene encoding a surface protein from the sexual stages of Plasmodium berghei. AB - The sexual stage-specific protein Pbs21 of the rodent malaria parasite Plasmodium berghei, expressed on the surface of zygotes and ookinetes, has been shown to induce an effective and long-lasting transmission blocking immunity. The gene encoding Pbs21 was cloned by screening a cDNA library prepared from enriched zygotes and ookinetes using the monoclonal antibody 13.1.15, which is capable of blocking subsequent parasite sexual development in the mosquito vector. The Pbs21 gene encoded a protein of 213 amino acids which contained a putative amino terminal signal sequence and a putative carboxy-terminal hydrophobic membrane anchor. The amino-acid sequence was characterised by a large number of cysteine residues which were organized into 4 epidermal growth factor-like domains. The spacing of the cysteine residues was highly conserved when compared to the 25-kDa ookinete proteins of Plasmodium falciparum (Pfs25), Plasmodium reichenowi (Prs25) and Plasmodium gallinaceum (Pgs25) which were approximately 45%, 45% and 40% homologous to Pbs21 respectively. The gene is located on chromosome 5 and cross hybridizes to a similarly defined gene unit in the other rodent malaria species Plasmodium chabaudi, Plasmodium vinckei and Plasmodium yoelii. The gene is internally disposed and not in the subtelomeric region of chromosome 5. The gene is transcribed in a stage-specific manner giving rise to an abundant 1.5-kb transcript. This mRNA is synthesised in the precursor cells to female gametes (gametocytes) however the protein is observed only after activation of the gametes, suggesting that translation of the mRNA is controlled by a post transcriptional process. The Pbs21 gene and the P. berghei parasite system provide an excellent vehicle for the study of stage-specific transcriptional and post-transcriptional control in malaria. PMID- 8341325 TI - Characterization of mevalonate-labeled lipids isolated from parasite proteins in Schistosoma mansoni. AB - Adult paired schistosomes incubated for 3 days in radiolabeled mevalonate can effectively label at least 2 major proteins with apparent sizes of 25 and 43 kDa. The 25-kDa mevalonate-labeled proteins comigrated with proteins that could be labeled with GTP. The lipids attached to these proteins were removed and resolved by HPLC and found to comigrate with known samples of farnesol and geranylgeraniol. Homogenates of the schistosome when incubated with labeled farnesol pyrophosphate effectively labeled a protein(s) with an apparent molecular weight of 43 kDa while homogenates incubated in the presence of labeled geranylgeranyl pyrophosphate-labeled schistosome proteins with an apparent molecular weight of 25 kDa. Our results demonstrate that Schistosoma mansoni has the ability to covalently attach farnesol and geranylgeranyl to low-molecular weight proteins. PMID- 8341326 TI - Mucin-like glycoproteins linked to the membrane by glycosylphosphatidylinositol anchor are the major acceptors of sialic acid in a reaction catalyzed by trans sialidase in metacyclic forms of Trypanosoma cruzi. AB - We have previously shown that 35- and 50-kDa glycoconjugates of cultured metacyclic trypomastigotes participate in the attachment of parasites to mammalian cells. Here we show that when metacyclic trypomastigotes are incubated with [3H]sialyllactose, most of the sialic acid is transferred to these 35/50-kDa molecules in a reaction catalyzed by a parasite transsialidase. The sialic acid is incorporated in oligosaccharides of about 10 glucose units in size that are released from the glycoconjugate by mild alkaline hydrolysis. Compositional analysis reveals that the 35/50-kDa molecules are highly glycosylated proteins rich in threonine, galactose, N-acetyl-glucosamine and sialic acid. These glycoproteins can be labeled in vivo with [3H]palmitate, and the labeled fatty acid is released by glycosylphosphatidylinositol specific phospholipases C. This result, associated with the fact that they contain mannose, ethanolamine, myo inositol, and lipid, indicate that these glycoproteins are anchored to the membrane by glycosylphosphatidylinositol. During cell invasion, these molecules appear to be capped and locally released by the parasite. PMID- 8341328 TI - Pathogenic Entamoeba histolytica: cDNA cloning of a histone H3 with a divergent primary structure. AB - Entamoeba histolytica has an unusual nuclear structure characterized by a low degree of chromatin condensation and the absence of stainable metaphase chromosomes. Although nucleosome-like particles were observed, no information about histones was available so far. In this paper we describe a cDNA clone with significant homology to H3 histones that was isolated from a library of pathogenic E. histolytica. The complete cDNA encodes a 15-kDa polypeptide, which like the histone sequence from Volvox carteri is shorter by one residue than the human homologue. The amino acid sequence has only 69% identity with human H3.3 histone and 67% identity with the human H3.1 histone. This is the highest degree of sequence divergence observed for any eukaryote H3 histone sequence. Our results indicate that this divergence may contribute to the unusual chromatin structure of E. histolytica. PMID- 8341327 TI - Effect of thapsigargin on calcium homeostasis in Trypanosoma cruzi trypomastigotes and epimastigotes. AB - By using the fluorescent calcium indicator fura-2, it was found that the concentration of free Ca2+ in the cytoplasm of Trypanosoma cruzi trypomastigotes incubated in the presence or absence of external calcium was maintained at very low levels (10-20 nM). When trypomastigotes were incubated in the presence of succinate and ATP and permeabilized with digitonin, they lowered the medium calcium concentration to a submicromolar level. In the presence of 1 microM FCCP the initial rate of Ca2+ sequestration by these permeabilized cells was very slow. When succinate alone was present, the initial rate of Ca2+ accumulation was slower than with ATP plus succinate, and the calcium set point was about 0.6 microM. The succinate dependence and FCCP sensitivity of the later Ca2+ uptake indicate that it may be exerted by the mitochondria. High concentrations of the tumor promoter thapsigargin slightly increased cytosolic Ca2+ in the presence of extracellular Ca2+ but had no effect on the FCCP- and oligomycin/antimycin A insensitive Ca2+ pool. In addition, when used at those concentrations (4-20 microM), thapsigargin was shown to release Ca2+ from the mitochondria and to decrease the inner mitochondrial membrane potential of trypomastigotes and epimastigotes as measured using safranine O. Despite the presence of inositol phosphates as determined by [3H]inositol incorporation, no IP3-sensitive Ca2+ release could be detected in trypomastigotes. PMID- 8341329 TI - Rapid isolation of DNA from trypanosomatid protozoa using a simple 'mini-prep' procedure. AB - Although several methods for isolating genomic DNA from trypanosomatid protozoa exist, all are time-consuming and cumbersome. Faster, simpler and efficient protocols for preparation of DNA from these protozoa are needed to ease the screening of mutants and transfectants. We describe the use of a bacterial lysis method to isolate chromosomal DNA from a wide range of trypanosomatids. The method is based on the finding reported by He et al., who noticed that phenol/chloroform treatment of Escherichia coli cells in the presence of LiCl and Triton X-100 solubilizes plasmid DNA, while precipitating unwanted chromosomal DNA and denatured cellular proteins. In applying this lysis method to the isolation of episomal DNA from transfected trypanosomatids, we found that, unlike bacterial genomic DNA, chromosomal DNA of trypanosomatids was soluble in the phenol/chloroform/Triton/LiCl mixture. This observation prompted us to use the bacterial lysis method as a routine protocol for extraction of DNA from trypanosomatids. PMID- 8341330 TI - Isolation from a Plasmodium chabaudi chromosome 7 specific library of a novel gene encoding a protein with multiple GGMP repeats homologous to hsp70. PMID- 8341331 TI - Isolation and characterization of a middle repetitive DNA element from Echinococcus granulosus. PMID- 8341332 TI - Sequence of a cDNA encoding beta-tubulin from Babesia bovis. PMID- 8341333 TI - Racial differences in the incidence of cardiac arrest and subsequent survival. The CPR Chicago Project. AB - BACKGROUND: Differences between blacks and whites have been reported in the incidence of several forms of cardiovascular disease, including hypertension and stroke. We examined racial differences in the incidence of cardiac arrest in a large urban population and in subsequent survival. METHODS: We collected data on all nontraumatic, out-of-hospital cardiac arrests in Chicago from January 1, 1987, through December 31, 1988, and compared the incidence and survival rates for blacks and whites. We examined the association between survival and race and seven other known risk factors by logistic-regression analysis. We computed incidence rates by coupling our data with U.S. Census population data. RESULTS: Our study population comprised 6451 patients: 3207 whites, 2910 blacks, and 334 persons of other races. The incidence of cardiac arrest was significantly higher for blacks than for whites in every age group. The survival rate after cardiac arrest was 2.6 percent in whites, as compared with 0.8 percent in blacks (P < 0.001). Blacks were significantly less likely to have a witnessed cardiac arrest, bystander-initiated cardiopulmonary resuscitation, or a "favorable" initial rhythm or to be admitted to the hospital. When they were admitted, blacks were half as likely to survive. The association between race and survival persisted even when other recognized risk factors were taken into account. We did not find important differences between blacks and whites in the response times of the emergency medical services. CONCLUSIONS: The black community in our study was at higher risk for cardiac arrest and subsequent death than the white community, even after we controlled for other variables. PMID- 8341334 TI - Prenatal determination of fetal RhD type by DNA amplification. AB - BACKGROUND: An RhD-negative woman whose partner is heterozygous may have preexisting anti-RhD antibodies that may or may not affect a subsequent fetus, depending on whether it is heterozygous. A safe method of determining fetal RhD type early in pregnancy would eliminate the risks to an RhD-negative fetus of fetal-blood sampling or serial amniocenteses. METHODS: We determined the RhD type in 15 fetuses using the polymerase chain reaction in amniotic cells and serologic methods in fetal blood collected simultaneously. In another 15 fetuses, the RhD type determined from chorionic-villus samples was compared with that identified by typing of DNA from the fetus itself. RESULTS: RhD typing of DNA from amniotic cells correctly indicated the serologic type in every fetus. Of 10 fetuses with RhD-negative mothers, 4 were identified as RhD-negative and 6 as RhD-positive. Of five fetuses with RhD-positive mothers, four were identified as RhD-positive and one as RhD-negative. There was also complete agreement between the results of RhD typing of DNA from chorionic-villus samples and the results of typing of DNA from fetal tissue. Eleven fetuses were RhD-positive, and 4 were RhD-negative. Four RhD positive fetuses had RhD-negative mothers. Three RhD-negative fetuses had RhD positive mothers. There was no contamination by maternal RhD-positive DNA of the samples from RhD-negative fetuses. CONCLUSIONS: Determining fetal RhD type in amniotic cells without invading the fetomaternal circulation is a reliable method that will be valuable in the management of Rh alloimmunization. PMID- 8341335 TI - Treatment of orthostatic hypotension with erythropoietin. AB - BACKGROUND AND METHODS: Patients with orthostatic hypotension caused by autonomic neuropathy frequently have a decreased red-cell mass. This would be expected to compromise their effective circulating blood volume and aggravate the orthostatic hypotension. We studied the effect of increasing the red-cell mass with erythropoietin, given subcutaneously in a dose of 50 U per kilogram of body weight three times a week for 6 to 10 weeks to eight patients with orthostatic hypotension--four men, one teenage boy, and three women (age range, 17 to 68 years). Four patients had type I diabetes mellitus and autonomic neuropathy, three patients had pure autonomic failure, and one patient had sympathotonic orthostatic hypotension. Seven patients received fludrocortisone (0.1 or 0.2 mg per day) before, during, and after the trial of erythropoietin. The red-cell volume, plasma volume, and hemodynamic response to orthostatic stress were measured before and after therapy. RESULTS: Erythropoietin increased the mean (+/ SD) hematocrit from 0.34 +/- 0.04 to 0.45 +/- 0.04 (P < 0.005) and increased the red-cell volume from 16.8 +/- 3.9 to 25.3 +/- 3.1 ml per kilogram (P < 0.005), but had no effect on plasma volume. The systolic blood pressure increased from 81 +/- 11 to 100 +/- 24 mm Hg (P < 0.01) and the diastolic blood pressure increased from 46 +/- 10 to 63 +/- 18 mm Hg (P < 0.01) while the patients were standing. The average systolic and diastolic blood pressure while the patients were supine did not increase significantly, although hypertension in the supine position developed in three patients. Orthostatic dizziness improved during treatment in six of the eight patients. CONCLUSIONS: In patients with orthostatic hypotension, increasing the red-cell volume with erythropoietin elevates blood pressure while standing. Possible long-term adverse effects are not known. PMID- 8341336 TI - Plasma renin activity and ischemic heart disease. AB - BACKGROUND: An earlier prospective study reported an association between high levels of plasma renin activity (as measured by the renin-sodium profile) and the incidence of myocardial infarction in patients with hypertension. We have investigated the relation between plasma renin activity and ischemic heart disease in the Northwick Park Heart Study. METHODS: The study included 803 white men 40 to 64 years of age selected from industrial workers in London. Plasma renin activity and established risk factors for ischemic heart disease were measured at entry, which was between 1972 and 1978. Ascertainment of the primary clinical end points of fatal or nonfatal myocardial infarction and sudden death from coronary causes was carried out until the end of 1991. RESULTS: In an analysis of the 86 first coronary events, we found an independent relation between higher systolic blood pressure and coronary end points (relative risk per 1 SD increase in blood pressure, 1.47; 95 percent confidence interval, 1.16 to 1.85; P < 0.001), but no relation between plasma renin activity and coronary end points (relative risk per 1 SD increase in the level of plasma renin activity, 1.04; 95 percent confidence interval, 0.84 to 1.30). In the 242 men who had hypertension of a degree similar to that of the subjects in the earlier prospective study of the renin profile, and in whom 44 of the 86 coronary events occurred, the relative risk of those in the highest as compared with the lowest third for plasma renin activity was 1.26 (95 percent confidence interval, 0.63 to 2.56). CONCLUSIONS: Our results suggest that there is no association between plasma renin activity and myocardial infarction or sudden death from coronary causes, at least in normotensive men. PMID- 8341337 TI - Images in clinical medicine. Endovascular stents for iliac arterial disease. PMID- 8341338 TI - Racial differences in the use of invasive cardiovascular procedures in the Department of Veterans Affairs medical system. AB - BACKGROUND: Previous studies have found racial differences in the use of invasive cardiovascular procedures, which may be due in part to the greater financial incentives to perform such procedures in white patients. In Department of Veterans Affairs hospitals, direct financial incentives affecting use of the procedures are minimized for both patients and physicians. METHODS: We conducted a retrospective analysis of the use of cardiovascular procedures among black and white male veterans discharged from Veterans Affairs hospitals with primary diagnoses of cardiovascular disease or chest pain during fiscal years 1987 through 1991. We used coded discharge data to determine whether cardiac catheterization, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting was performed during or immediately after such admissions. We used logistic-regression analysis to adjust for the primary discharge diagnosis, the presence of coexisting conditions, age, marital status, type of eligibility to receive care at Veterans Affairs hospitals, geographic region, and whether the hospital was equipped to perform bypass surgery. We classified the primary diagnosis as myocardial infarction, unstable angina, angina, chronic ischemia, chest pain, or "other" cardiovascular diagnosis. RESULTS: After we adjusted for all the potential confounders, we found that white veterans were more likely than black veterans to undergo cardiac catheterization (odds ratio, 1.38; 95 percent confidence interval, 1.34 to 1.42), angioplasty (odds ratio, 1.50; 95 percent confidence interval, 1.38 to 1.64), and coronary artery bypass surgery (odds ratio, 2.22; 95 percent confidence interval, 2.09 to 2.36). CONCLUSIONS: Even when financial incentives are absent, whites are more likely than blacks to undergo invasive cardiac procedures. These findings suggest that social or clinical factors affect the use of these procedures in blacks and whites. PMID- 8341339 TI - American trypanosomiasis (Chagas' disease)--a tropical disease now in the United States. PMID- 8341340 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 34-1993. A 36-year-old man with AIDS and respiratory failure. PMID- 8341341 TI - Adults with tetralogy of Fallot--repaired, yes; cured, no. PMID- 8341342 TI - Heart disease in black and white. PMID- 8341343 TI - The new and the old--molecular diagnostics and hemolytic disease of the newborn. PMID- 8341344 TI - Sexual harassment in medical training. PMID- 8341345 TI - Sexual harassment in medical training. PMID- 8341346 TI - Sexual harassment in medical training. PMID- 8341347 TI - Sexual harassment in medical training. PMID- 8341348 TI - Life support for patients with cervical-level quadriplegia. PMID- 8341349 TI - Life support for patients with cervical-level quadriplegia. PMID- 8341351 TI - Life support for patients with cervical-level quadriplegia. PMID- 8341350 TI - Life support for patients with cervical-level quadriplegia. PMID- 8341352 TI - Life support for patients with cervical-level quadriplegia. PMID- 8341353 TI - Graft-versus-host disease. PMID- 8341354 TI - Growth hormone, insulin-like growth factor I, and benign intracranial hypertension. PMID- 8341355 TI - Geographic variations in payments to physicians. PMID- 8341356 TI - Geographic variations in payments to physicians. PMID- 8341357 TI - Geographic variations in payments to physicians. PMID- 8341358 TI - Geographic variations in payments to physicians. PMID- 8341359 TI - Use of cocaine during pregnancy. PMID- 8341360 TI - Activation of Immediate Early Genes by Drugs of Abuse. Technical review. Rockville, Maryland, June 3-4, 1991. PMID- 8341362 TI - Mechanisms of opioid-mediated antinociception: correlation of Fos expression and behavior. PMID- 8341361 TI - c-Fos and Fos-related antigens as markers for neuronal activity: perspectives from neuroendocrine systems. PMID- 8341363 TI - The ontogeny of immediate early gene response to cocaine: a molecular analysis of the effects of cocaine on developing rat brain. PMID- 8341364 TI - NMDA receptor blockade prevents translation, but not transcription, of the c-fos gene following stimulation with multiple extracellular signals in cultured cortical neurons: implications for plasticity and molecular memory. PMID- 8341366 TI - Everything activates c-fos--how can it matter? AB - It is probably safe to say that the regulation of c-fos expression by drug treatment and other stimulus paradigms has biological specificity and mechanistic significance. However, as this brief essay makes clear, the immunohistochemical detection of c-fos is only the tip of the biological iceberg. IEGs deserve to be studied as critical components of the intracellular signaling machinery that may transduce intercellular signals, including those produced by drugs of abuse, into longer term changes in cellular function. However, the study of IEG expression must be related to biologically significant target genes and must be complemented by the study of phosphorylation of constitutively expressed transcription factors. Moreover, as illustrated by the proenkephalin gene, the regulation of genes that play important roles in differentiated cell function may differ depending on which cell types and stimulus conditions are investigated. Finally, attention must be paid to the complexities of gene regulation under conditions of repetitive and chronic stimulation if phenomena such as the neural substrates of drug dependence are to be understood. PMID- 8341365 TI - Induction and suppression of proto-oncogenes in rat striatum after single or multiple treatments with cocaine or GBR-12909. PMID- 8341367 TI - Regulation of immediate early gene expression. AB - From this brief overview of the regulation of the c-fos promoter, it can be seen that the regulation of early-response genes is a complex affair. Therefore, it is not easy to predict from the upstream sequence of a given early-response gene exactly which elements are responsible for responding to what signals in a given cell type. However, from studies of other early-response genes, it is clear that several of the elements found upstream of c-fos appear frequently and are important in the regulation of other early-response genes. For instance, the zif/268 gene has four separate CArG boxes that are similar to fos. These CArG boxes can function in the serum and TPA response, but interestingly, they are not imbedded in a region of dyad symmetry as in c-fos (Christy and Nathans 1989). Upstream of the c-jun oncogene is an AP-1 site that can modulate the expression and induction of this gene and is responsive to TPA (Angel et al. 1988). Moreover, other studies suggest that cAMP-mediated signals can repress induction of c-jun through this element (de Groot et al. 1991; Mechta et al. 1989). This would explain why in certain circumstances, such as depolarization of PC12 cells or in the striatum in response to cocaine, there is an uncoupling of the induction of c-jun and jun-B. Depolarization induces c-fos and jun-B but not c jun; however, growth factors such as NGF can induce all three genes in the same cell (Bartel et al. 1989). Upstream of the jun-B gene there does not appear to be an SRE, but there is a new element that can be responsive to both cAMP and phorbol esters (de Groot et al. 1991). Genes such as c-myc, JE, and KC have no consensus SREs upstream, and the regulatory elements responsible for the induction of these genes have not been clearly identified (Rollins et al. 1988). However, there is some evidence from the c-myc gene that the E2F binding sites are important for its regulation by serum (Mudryj et al. 1990; Sacca and Cochran 1990). In addition, there are two SIF sites upstream of the c-myc proto-oncogene (B.H. Cochran and T.E. Hayes, unpublished results). Upstream of the nur-77 gene there are no SREs, but there are four potential calcium/CRE-like elements (Watson and Milbrandt 1989).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8341368 TI - Immediate early genes: their involvement in physiological and pathological responses in the nervous system. PMID- 8341369 TI - Immediate early gene activation and long-term changes in neural function: a possible role in addiction? PMID- 8341371 TI - Presentation of the Morrison Award. PMID- 8341370 TI - Regulation of neural gene expression in opiate and cocaine addiction. PMID- 8341372 TI - What's a radical behaviorist like you doing in a nice pharmacology club like C.P.D.D.? PMID- 8341373 TI - Dependence studies of new compounds in the rhesus monkey, rat and mouse (1992). PMID- 8341374 TI - Genetic approaches to understanding the actions of drugs of abuse. PMID- 8341375 TI - The National Institute on Drug Abuse 1992--focus on the future: a steadfast commitment to research. PMID- 8341376 TI - Credentials committee--"get involved". AB - The purpose of this information is to make a plea to physicians to get involved with your Credentials Committee. Your active interest and participation will help physicians maintain control of this important process. If you are not able to be an active member of the committee, be sure that there is someone on the committee who is looking our for your interests. PMID- 8341377 TI - Neonatal group B streptococcal infections: case report and review of the literature. PMID- 8341378 TI - Update on neonatal blood transfusions. PMID- 8341379 TI - Serum lipids predict cardiac death in diabetic patients on maintenance hemodialysis. Results of a prospective study. The German Study Group Diabetes and Uremia. AB - The objective of this study was to measure cholesterol concentrations in diabetic patients at the beginning of maintenance hemodialysis treatment and to define their role as predictors of subsequent cardiac death on maintenance hemodialysis. The design of this study consisted of a prospective study of all consecutive diabetic patients newly admitted to 28 German dialysis centers between January 1985 and October 1987. The patients were examined on admission and subsequently followed for 45 months on dialysis. This study included 196 patients, 67 type I (43 male, 24 female, median age 49 years, range 22-73) and 129 type II (54 male, 75 female, aged 64 years, range 37-82). Lipids (total cholesterol, triglycerides low-density lipoprotein (LDL) cholesterol high-density lipoprotein (HDL) cholesterol apolipoprotein B and A and anthropometric indices (body mass index, triceps skinfold thickness) were measured. The outcome was death, i.e., cardiovascular (myocardial infarction, sudden death, other cardiac causes, stroke) and noncardiovascular death during a 45-month follow-up. At the start of treatment, total cholesterol, triglycerides LDL cholesterol, LDL/HDL ratio and apolipoprotein B were significantly higher in diabetics than in healthy controls or patients with standard primary renal disease starting dialysis. Only minor differences were found between males and females and type I and type II diabetics. Fourty-three percent of type I and 50% of type II diabetics died, 61% from cardiovascular causes, mostly myocardial infarction (in 40% reinfarction) and sudden death. On admission, diabetics subsequently dying from myocardial infarction had significantly higher median cholesterol than survivors, i.e., 259 versus 222 mg/dl, and higher LDL cholesterol, LDL/HDL ratio and apolipoprotein B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341380 TI - Cigarette-smoking affects platelets and endothelium in chronic hemodialysis patients. AB - Previous work has shown that cigarette-smoking affects platelets and endothelium in men and women without renal failure. The present study compared 10 male habitual smokers receiving maintenance hemodialysis for chronic renal failure with 11 healthy male habitual smokers before and after controlled cigarette smoking after a 12-hour period of abstinence. Collagen-induced platelet aggregation was not significantly different in the two groups of men before smoking. The platelet aggregate ratio was lower and the plasma concentration of platelet factor 4 was higher in the dialysis patients than in the healthy men (p < 0.05). Mean or median values before and after cigarette smoking by the dialysis patients were 42 and 62 chart units for collagen-induced platelet aggregation, 0.88 and 0.77 for the platelet aggregate ratio, 6.2 and 8.5 ng/ml for the plasma concentration of platelet factor 4, 0.8 and 1.7 per counting chamber for the endothelial cell count and 4 and 37 ng/ml for the plasma nicotine concentration (each p < 0.01). None of the changes which occurred in the dialysis patients was statistically significantly different from those in the healthy men. We conclude that cigarette-smoking has similar effects on platelets and endothelium in patients receiving maintenance hemodialysis and in healthy controls. PMID- 8341381 TI - Compliance in hemodialysis patients: a multivariate regression analysis. AB - Successful treatment of patients with end-stage renal failure requires, in addition to dialysis, strict control of dietary, fluid and medication intake. In the present study we measured, in 50 chronic hemodialysis patients, serum potassium (K), serum phosphate (PO4) and interdialytic weight gain as indices of diet, medication and fluid compliance, respectively. Dietary compliance did not correlate with fluid or medication compliance, whereas fluid intake and medication compliance were related (p = 0.01). Age, time on dialysis, place of birth and whether the patient came accompanied or not to the dialysis unit were the main variables affecting serum K levels. Sex, ethnic origin and education significantly affected serum PO4. Sex, place of birth, marital status, number of children and years of education affected fluid intake. The compliance of the hemodialysis patient with different aspects of his regimen is thus multifactorial. Attempts to improve compliance and thus reduce morbidity and mortality should be aimed at identifying the population with low compliance and exposing them to educational programs. PMID- 8341382 TI - Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding. AB - 107 hemodialysis patients at high risk for intradialytic bleeding due to previous surgery or active bleeding from other sites were treated with nafamostat mesilate (FUT-175; FUT) as hemodialysis anticoagulant for 2 weeks. In contrast to heparin. FUT prolonged clotting times only in the extracorporeal circuit. Clotting times were not prolonged even at the conclusion of the treatment, and bleeding from the puncture site after removal of the needle was shorter than with heparin. The exacerbation of bleeding by hemodialysis was noted in only 21 out of 573 hemodialysis procedures (3.7%), and 134 of 145 hemodialysis procedures (92.4%) with active bleeding were successfully completed without increasing the bleeding. Adverse effects of FUT were noted in only 6 cases (5.6%) or 1.2% of HD procedures. These results indicate that FUT is a very useful anticoagulant for HD, especially in patients with high risk of bleeding. PMID- 8341383 TI - Serum vanadium levels in chronic hemodialysis patients. AB - Serum vanadium, aluminum, silicon and beta 2-microglobulin levels as well as the red cell count, hemoglobin and systolic blood pressure were simultaneously measured in 80 chronic hemodialysis patients. The serum vanadium level was positively correlated with the serum levels of aluminum, silicon and beta 2 microglobulin as well as the systolic blood pressure, and was inversely correlated with the red cell count and hemoglobin. The mean serum vanadium level was 18.4 +/- 7.6 ng/ml before hemodialysis and decreased to 13.0 +/- 5.30 ng/ml at the completion of dialysis. The dialysate vanadium level increased from 0.4 +/ 0.2 (inflow) to 1.0 +/- 0.4 ng/ml (outflow). It was concluded that vanadium was transferred from blood to dialysate when purified water was used in the preparation of the dialysate. PMID- 8341384 TI - Questionable role of soy protein in childhood IgA nephropathy. AB - By means of indirect immunofluorescence, the glomerular deposition of soy protein was studied in renal biopsy specimens from 16 children (aged 4-18 years) with IgA nephropathy. In addition, serum anti-soy protein IgA antibody was measured by enzyme-linked immunosorbent assay. Glomerular immunofluorescence for soy protein was not found in any of the preparations studied, both without and with citrate buffer treatment, and there was no significant difference in the concentration of serum anti-soy protein IgA antibody between the 13 patients studied and 13 age- and sex-matched controls. It is thus unlikely that soy protein plays a crucial role in the pathogenesis of childhood IgA nephropathy. PMID- 8341385 TI - Prognosis of children with acute renal failure: a study of 138 cases. AB - Acute renal failure (ARF) in children has a poor prognosis in spite of modern therapeutic techniques. For this reason, it would be useful to have prognostic indicators early in the course of the disease, in order to identify those patients that could benefit most from aggressive treatment. In an attempt to establish valid prognostic factors, we prospectively studied 138 cases of ARF in children. We examined age, sex, etiology of ARF, previous surgery, prerenal origin, clinical situation of the patient when first seen by the nephrologist and complications. All these variables were statistically analyzed individually by univariate tests and, except for sex and complications, also by multiple regression analysis. Median age of the patients was 26 months. The etiology of ARF was nephropathy in 16, tumor in 14, cardiopathy in 85 and other causes in 23 cases. For analysis, patients were divided into patients with and without prerenal ARF. In the prerenal group, mortality-related factors were hypotension, need for ventilatory support, age less than 1 month and serum values of creatinine. In the nonprerenal ARF group, the need for assisted ventilation and the need for dialysis correlate positively with the mortality, while an exclusive nephrological etiology was associated with less probability of death. PMID- 8341386 TI - Altered metabolism in the ex vivo remnant kidney. I. Effects of time, substrate and perfusion pressure. AB - Oxygen consumption is increased in the rat remnant kidney (RK), but the basis of this enhanced metabolic activity has not been defined fully. To characterize the hypermetabolism further, isolated RK and normal kidneys (NK) were perfused using a range of perfusion pressures and substrates, and at varying times after 5/6 nephrectomy. Altered and increased RK metabolism was found as early as 1 week after 5/6 nephrectomy. The rate of net glucose consumption was higher in RK than NK (e.g., 0-30 min, 2.42 +/- 0.28 vs. 1.21 +/- 0.33 mumol.min-1 x g-1), a difference not explained by changes in oxygen delivery or glycosuria. Ammonia production was significantly greater early in perfusion in RK than NK. Calculated nephron oxygen consumption (QO2) was greater in RK than NK for all substrates tested (e.g., pyruvate 5 mM: 552.3 +/- 43.1 vs. 173.3 +/- 25.6 pmol.min-1, p < 0.001). When considered together, site I mitochondrial substrates supported QO2 and net sodium reabsorption (TNa+) better than site II substrates. In RK, QO2 did not change with increasing perfusion pressure, and TNa+ rose only slightly for pressures > or = 120 mm Hg. In summary, RK hypermetabolism is characterized by increased oxygen consumption, glycolysis and ammoniagenesis, is not substrate specific and does not appear to be an artefact of the altered physiology of remnant perfusion. PMID- 8341388 TI - Comparison of renal effects of creatinine, creatol and methylguanidine in rats with adenine-induced chronic renal failure. AB - Creatinine (Cr), creatol and methylguanidine (MG), which accumulate in the body with the progress of renal failure after adenine administration, were given separately to rats in order to compare their toxicities. Food containing adenine was given to rats for 20 days to induce renal failure. Then each of the test substances was administered intraperitoneally, and renal function of the rats was determined. The changes in glomerular filtration rate, renal plasma flow and renal blood flow after administration of Cr were only slight in comparison with those of the control group. Creatol or MG administration induced a significant decrease in renal function. In addition, the level of MG in serum, liver and kidney was extraordinarily high in rats given creatol or MG. The toxic effects are discussed on the basis of these results. PMID- 8341387 TI - Altered metabolism in the ex vivo remnant kidney. II. Effects of metabolic inhibitors and dietary protein. AB - To understand further the contribution of heightened net sodium reabsorption (TNa+) and other nontransport processes to increased and altered metabolic activity of the rat remnant kidney (RK), isolated RK and normal kidneys (NK) were perfused with and without metabolic inhibitors and following 4 weeks of low (12%) or high (40%)-protein diet. 3-Mercaptopicolinate (200 microM) and 2-deoxyglucose (200 microM) reduced glucose production and consumption, respectively, without altering oxygen consumption (QO2). Ouabain reduced TNa+ and QO2 in NK but not RK, and increased glucose consumption in RK (by 67%, p < 0.02, n = 12) and NK (by 54%, p < 0.05, n = 12). Raising perfusate pH by 0.3 U to 7.65 increased glucose production in RK but not NK and reduced TNa+ in NK but not RK. Dietary protein restriction reduced QO2 (2.18 +/- 0.29 vs. 4.13 +/- 0.20 mumol-1 x min-1 x g-1, p < 0.001), TNa+ (8.74 +/- 4.39 vs. 38.83 +/- 8.32, p < 0.01) and ammoniagenesis (0 30 min, 0.16 +/- 0.05 vs. 0.32 +/- 0.10, p < 0.05) in RK, but not NK. In summary: (1) responses to ouabain and alkalosis, but not other metabolic inhibitors, were quite distinct in remnant versus normal kidneys, and (2) protein restriction limited sodium-transport-dependent and -independent hypermetabolism in RK. PMID- 8341389 TI - Castration attenuates proteinuria and glomerular injury in hyperlipidemic male Imai rats. AB - Hyperlipidemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially in males. We investigated the effect of castration on spontaneous proteinuria and progressive renal injury in male Imai ats. Male Imai rats (n = 16) were castrated at 5 weeks of age. Body weight, blood pressure, urinary protein excretion and serum constituents were checked and compared with sham-operated control rats (n = 16) up to 24 weeks. Sham-operated group 1 (n = 5) and castrated group 2 (n = 6) underwent morphological study after 16 weeks of observation and sham-operated group 3 (n = 11) and castrated group 4 (n = 10) were followed for an additional 8 weeks and used for morphological study. Growth rate was significantly stunted in castrated rats as compared with the controls. Castration significantly reduced proteinuria almost throughout the experiment (167 +/- 84 vs. 46 +/- 24 mg/kg/day, p < 0.001, at 8 weeks and 688 +/- 211 vs. 458 +/- 97, p < 0.01, at 20 weeks). The glomerulosclerosis index was significantly higher in sham-operated control rats than in castrated rats (28.8 +/- 18.0 vs. 7.3 +/- 3.1, p < 0.01, at 16 weeks, and 92.1 +/- 35.5 vs. 39.5 +/- 8.9, p < 0.001, at 24 weeks). There were no significant differences in blood pressure, serum cholesterol, plasma renin activity, plasma somatomedin C levels between the two groups. These results raise the possibility that sex hormones may partly contribute to spontaneous proteinuria and progressive renal injury in male Imai rats. PMID- 8341390 TI - Effects of furosemide on renal oxygen consumption after ischemia in normal and streptozotocin diabetic rats. AB - Normal and streptozotocin diabetic rats were subjected to ischemic injury by unilateral renal artery occlusion for 60 min. The cortical and the medullary oxygen consumption (QO2) in the postischemic and the control, contralateral nonischemic, kidneys were measured 1 h, 1 day, and 1, 2 and 4 weeks for normal rats and 1 day, and 1 and 4 weeks for diabetic rats after ischemia. The effects of furosemide on QO2 of the cortex and the medulla of normal and diabetic rats were studied. The diabetic kidney was more vulnerable to ischemic injury than the normal kidney. Furosemide-sensitive active transport function in the medulla of the diabetic kidney was higher than that of the normal kidney. Furosemide did not decrease the cortical QO2 significantly in the control and the postischemic kidneys of normal and diabetic rats. In contrast, the medullary QO2 of the control kidney in both rats was significantly reduced by furosemide at every period after ischemia. In the medullary QO2 of the postischemic kidney, there were no significant decreases at any period after ischemia in the diabetic rats and only after a 1-hour period for normal rats. However, 4 weeks after ischemia, there was no statistically significant difference in the medullary QO2 inhibition by furosemide between the control and the postischemic kidneys in both normal and diabetic rats. We conclude that the furosemide-sensitive active transport function in the medulla recovers by the 4th week after ischemia in normal and diabetic rats. PMID- 8341391 TI - A case of pheochromocytoma of the urinary bladder in a long-term hemodialysis patient. AB - The development is reported of a pheochromocytoma of the urinary bladder in a 33 year-old patient with systemic lupus erythematosus who had undergone long-term hemodialysis. A hypertensive episode followed by defecation was demonstrated by the monitoring of blood pressure with a portable automated sphygmomanometer without elevation of plasma catecholamines. The tumor was surgically removed and normalization of the patient's blood pressure followed. Thus, monitoring of blood pressure for 24 h proved useful for the diagnosis of pheochromocytoma and, in particular, of paroxysmal hypertension. PMID- 8341392 TI - Renal hypouricemia with both drug-insensitive secretion and defective reabsorption of urate: a novel type of renal hypouricemia. AB - Renal handling of urate in the hypouricemic patient with increase in both urate clearance (Cur) and Cur/creatinine clearance (Ccr) and normal urinary excretion of urate was studied according to the pharmacological evaluation. In the present case there was no response of urate excretion to either pyrazinamide or probenecid. Both furosemide and prednisolone could not alter Cur and Cur/Ccr. Administration of inosine could have increased Cur, which was greater than Ccr. These results suggest that the present case had the defect of both pre- and postsecretory reabsorption of urate, accompanied by the existence of drug insensitive secretion of urate, which is different from hitherto known types of renal hypouricemia, i.e. a novel type of renal hypouricemia. PMID- 8341393 TI - Chronic renal insufficiency after an episode of macroscopic hematuria in IgA nephropathy. AB - Several cases of acute renal failure associated with episodes of macroscopic hematuria (EMH) in IgA nephropathy (IgAN) have been reported; in every case renal function returned to normal. We report 2 cases with previous normal renal function that developed acute renal failure during EMH of 17 and 30 days duration, respectively. Renal biopsies showed mesangial proliferation with IgA deposits, crescents in 10-15% of glomeruli and a marked tubular necrosis with red blood cell casts obstructing the lumen in 30-45% of tubules. Although renal function improved after EMH cessation, it did not recover previous normal values. Thus, EMH can produce permanent loss of renal function in patients with IgAN. PMID- 8341394 TI - Wegener's granulomatosis with antiproteinase-3 antibodies occurring after Hodgkin's disease. AB - We describe the first association between Hodgkin's lymphoma and Wegener's granulomatosis, heralded by renal involvement. A 43-year-old man developed rapidly progressive glomerulonephritis requiring chronic hemodialysis 8 months after remission of Hodgkin's lymphoma. At that moment, no extrarenal involvement was found, despite extensive investigation. Antineutrophil cytoplasm antibodies were positive, without specificity for proteinase-3 or myeloperoxydase. Six months after beginning hemodialysis, multiple pulmonary nodules appeared, along with rapid clinical worsening. A surgical biopsy was performed which disclosed a giant cell granuloma. Antimyeloperoxydase antibodies remained negative, whereas proteinase-3 antibodies became positive. Wegener's granulomatosis was diagnosed and treatment with cyclophosphamide and steroids was started. Clinical and radiological improvement occurred promptly. Eleven months after treatment, both Wegener's disease and Hodgkin's lymphoma remained in remission. PMID- 8341396 TI - Use of tissue plasminogen activator for reopening of clotted dialysis catheters. AB - The use of central venous catheters as permanent vascular access in chronic hemodialysis is complicated by clotting. We have tried a nonallergenic thrombolytic agent, tissue plasminogen activator (t-PA), to dissolve catheter luminal thrombosis. Eight patients, 7 in chronic hemodialysis and 1 treated by immune adsorption had 18 treatments with locally applied t-PA (2 mg/2 cm3). Fifteen out of 16 treatments with longer bolus dwell than 60 min were successful. No side effects occurred. t-PA dissolves clot formation efficiently and safely, the drug is nonallergenic and can therefore be given repeatedly. PMID- 8341395 TI - Partial correction of dialysis-associated anaemia does not reduce erythropoietin dose or the incidence of side effects. AB - We examined the hypothesis that administering epoetin to maintain a lower target haemoglobin (Hb) results in a reduced side effect profile and a lower maintenance epoetin dose. We report a prospective study of 14 haemodialysis patients assessing epoetin dose efficiency and side effect profile of partially correcting dialysis-associated anaemia. Initial Hb was 6.2 +/- 0.6 g/dl (mean +/- 1 SD). Intravenous epoetin was commenced at 120 IU/kg/week in 3 divided doses and titrated to achieve a target Hb of 8 g/dl. Follow-up was 24 weeks. The final Hb was 8.7 +/- 0.8 g/dl. The peak epoetin dose was 196 +/- 86 IU/kg/week with a maintenance dose of 141 +/- 71 IU/kg/week. Therapy was associated with hypertension--5 patients (32%); seizures--1 patient (6%) (withdrawn from therapy), and temporary iron deficiency--4 patients (35%). Iron deficiency was corrected with oral therapy. There was 1 treatment failure. Comparable conventional regimens use 100-200 IU/kg to maintain the Hb at 10-13 g/dl and have a similar incidence of side effects. We concluded that reducing the target Hb in order to decrease epoetin requirements is not justified as it offers no benefit over conventional Hb targets in terms of dose requirements or side effects. PMID- 8341397 TI - Vesicoureteric reflux in a grafted kidney as a cause of massive hematuria: a case report. PMID- 8341398 TI - Acute renal failure as first clinical manifestation of the primary antiphospholipid syndrome. PMID- 8341400 TI - Maxillary brown tumor as manifestation of renal osteodystrophy. PMID- 8341401 TI - Spontaneous retropharyngeal bleeding in a patient on chronic hemodialysis. PMID- 8341399 TI - Excess purine degradation in muscle of chronic hemodialysis patients. PMID- 8341402 TI - Glomerulosclerosis and lipid peroxidation. PMID- 8341404 TI - Parenteral iron during hemodialysis. PMID- 8341403 TI - A case of crescentic glomerulonephritis associated with polymyositis. PMID- 8341405 TI - Long-term evolution of erythropoietin after successful renal transplantation. PMID- 8341406 TI - Angiographically demonstrable bilateral renal aneurysms in a patient with diabetic nephropathy. PMID- 8341407 TI - Concurrent renal sarcoidosis and lupus nephritis. PMID- 8341408 TI - Elevated circulating levels of hyaluronan in long-term hemodialysis patients with dialysis-associated arthropathy: what does it mean? PMID- 8341409 TI - Lymphorrhea following percutaneous right supraclavicular hemodialysis catheter placement. PMID- 8341410 TI - Radial arterial spasm in uremic patients undergoing construction of arteriovenous hemodialysis fistulas: diagnosis and prophylaxis with intravenous nicardipine. AB - Radial arterial spasm in uremic patients undergoing construction of internal arteriovenous (AV) dialysis fistulas was investigated transcutaneously using ultrasonic Doppler flowmetry. In 5 of 15 patients, radial arterial blood flow was significantly decreased 5 min after anastomosing the radial cephalic vein with the radial artery (14.3 +/- 4.5%, mean +/- SE, of the initial value; p < 0.001 vs. the initial blood flow), indicating vasospasm. Vasospasm disappeared 20 min after anastomosing. In 10 patients who were continuously given nicardipine intravenously (1 microgram/kg/min) during surgery, vasospasm did not occur. Arterial blood flow was significantly increased in patients who received nicardipine as compared with patients who did not receive nicardipine and did not have vasospasm, both at 10 min (171.2 +/- 16.2 vs. 124.3 +/- 11.9%, p < 0.05) and at 20 min (176.5 +/- 17.6 vs. 130.2 +/- 11.2%, p < 0.05) after anastomosing. Mean blood pressure was significantly reduced without causing hypotensive symptoms in patients who received nicardipine as compared with patients who did not receive nicardipine and did not have vasospasm. Our study suggests that ultrasonic Doppler flowmetry is useful for diagnosing vasospasm in patients undergoing the creation of AV fistulas and that nicardipine may be effective in preventing vasospasm safely. PMID- 8341412 TI - Target detection in left and right hemispace: effects of positional pre-cuing and type of background. AB - The two experiments reported here examined the degree to which detection of targets by the right hemisphere can be characterized as occurring at the global level and detection by the left hemisphere can be characterized as occurring at the local level. Although the results provided some evidence for such a dichotomy, these hemispheric differences in processing were modified by the overall configuration in which the item is embedded, the nature of the background, and whether a precue indicates the probable location of the target. The findings are discussed in relation to current theories of hemispheric differences in spatial processing. PMID- 8341411 TI - Strategic search and retrieval inhibition: the role of the frontal lobes. AB - Recall of words from categorised lists was examined in 77 patients and 12 normal control subjects. In Experiment 1, both left temporal-lobe excisions that included the hippocampus (LTH) and left frontal-lobe removals (LF) impaired free recall, but the LF group performed normally when encoding and retrieval strategies were supplied. In Experiment 2, experimentally induced interference during cued recall abnormally hampered performance for the LF, but not for the LTH group. Subsequent removal of the interfering cues resulted in improved performance for the LF group. Thus, the integrity of the left frontal lobe seems indispensable for normal strategic retrieval and for the suppression of potentially interfering items in verbal memory. PMID- 8341413 TI - Corpus callosum morphometry and dichotic listening performance: individual differences in functional interhemispheric inhibition? AB - We examined the relationship between midsagittal corpus callosum area, as seen by magnetic resonance imaging, and behavioral laterality effects from a dichotic listening task requiring cross-callosal relay of an auditory signal, in 60 healthy young adults. Four patients with complete forebrain commissurotomy were also given the dichotic listening task, confirming that in this task, the report of left ear items is dependent on callosal pathways. Contrary to our predictions, callosum measures were unrelated to either a laterality measure or to inferior (typically left) ear performance. Surprisingly, superior (typically right) ear accuracies, which do not depend on cross-callosal sensory transfer, were significantly and negatively correlated with callosum size. These findings show that normal variations in callosum size do not appear to contribute significantly to individual differences in hemispheric specialization. Callosum size may, instead, be associated with degree of functional interhemispheric inhibition. PMID- 8341414 TI - A material-control single-case study of the efficacy of treatment for written and oral naming difficulties. AB - Twenty-two right-handed aphasics with written and/or oral naming difficulties were treated with a traditional language therapy: copying and repetition of words. The efficacy and maintainability of the treatment were evaluated using a variation of the single-case design, which was termed the material-control single case design. Effectiveness of the treatment for written naming difficulty was demonstrated for 9 of 21 subjects in a first treatment and 3 of 14 subjects in a second treatment. Three of the 14 subjects benefitted overall from both treatments in written naming. In oral naming, 2 of 18 subjects responded well to the first treatment while 2 of 16 responded well to the second treatment. One of the 16 subjects showed benefits from both the first and second treatments in oral naming. Although written and oral naming disturbances were difficult to improve using ordinary language treatment, a small proportion of subjects clearly showed effectiveness of the therapy. Maintenance of the effects of treatment was observed in all of the improvers. PMID- 8341415 TI - Visual object agnosia, prosopagnosia, achromatopsia, loss of visual imagery, and autobiographical amnesia following recovery from cortical blindness: case M.H. AB - A number of higher visual deficits accompanied by severe retrograde autobiographical memory loss following bilateral medial occipital infarctions are described in case M.H. Assessment of M.H.'s visual object agnosia and prospagnosia suggested that he was unable to integrate the elements of a percept to form a meaningful whole. This deficit may occur at the level the percept is encoded into the visual buffer and inspected. M.H. also describes a loss of visual memories, and it is hypothesized that this may similarly be a result of an inability to integrate the elements of the visual representation (e.g. of an object or face) following its generation from long-term visual memory store into the visual buffer. M.H.'s retrograde autobiographical memory loss is postulated to be a consequence of the severe impoverishment of episodic memories that must occur when events originally stored multimodally, must be recalled without any visual component. PMID- 8341416 TI - Neuroendocrine brain asymmetry and physical complaints. AB - It was examined whether there is an association between physical health and alterations of normal brain asymmetry in cerebral control of neuroendocrine activity. In particular, it was studied whether right-handed subjects showing a high amount of physical complaints and recurrent diseases differ in direction and degree of brain asymmetry in cerebral control of cortisol secretion from subjects with only few physical complaints. Lateralized brain activation was achieved by presenting an emotionally aversive film to the subjects' left or right visual hemifield, using a technique for lateralizing visual input that allows prolonged viewing while permitting free ocular scanning. Results revealed a clear association between a high degree of physical complaints and altered brain asymmetry in cerebral control of neuroendocrine activity. PMID- 8341418 TI - Equivalent perceptual asymmetries for free viewing of positive and negative emotional expressions in chimeric faces. AB - Research employing chimeric stimuli (in which smiling and neutral half-faces are paired) has demonstrated greater influence of the left half-face in determining perceived intensity of expression. To date, no studies have examined how emotional expressions other than happiness are perceived in this format. Right handed subjects viewed chimeric faces depicting both positive (happiness, pleasant surprise) and negative (sadness, anger) emotions in a free vision task. Results indicated a left half-face bias for all four emotions, supporting the hypothesis of a greater right hemisphere role in emotional perception. The lack of differences in strength of left half-face bias as a function of the specific emotion depicted suggests that results obtained with typical chimeric half-face paradigms can be generalized to emotions other than happiness. PMID- 8341417 TI - Visual discrimination impairments following lesions of the superior temporal sulcus are not specific for facial stimuli. AB - Six rhesus monkeys took part in an experiment on visual learning. In three of the monkeys the part of the superior temporal sulcus in which many of the cells respond selectively to some aspect of faces was removed, while the remaining three animals served as unoperated controls. In Experiment 1 they learned a series of two-choice visual discriminations between patterns. The animals with lesions of the superior temporal sulcus were markedly impaired. The discriminations were of two types: in the first, the discriminanda differed in shape (e.g. Y and 3), while in the second they differed only in their orientation (e.g. ). Unlike animals with lesions to the neighbouring inferior temporal cortex who are impaired on shape but not orientation discriminations, animals with lesions of the superior temporal sulcus were equally impaired on both types of discrimination. In Experiment 2 the same six animals learned a series of discriminations between discriminanda which consisted of photographs of pairs of eyes. Each discrimination was between a set of eyes which looked directly at the viewer and a set in which the gaze was laterally averted to varying degrees. Again, animals with lesions of the superior temporal sulcus showed a marked impairment. We conclude that this impairment may be a general impairment in two choice visual discrimination learning, rather than a selective impairment in discrimination of eye gaze. This result warns against a simple interpretation of the function of this area as a "face area", concerned only, or chiefly, with the perception and significance of parts of the body, notably faces, and their movements. PMID- 8341420 TI - Ankyrin immunoreactivity in adult rat cerebellum. AB - An antibody recognizing all ankyrin isoforms was employed to localize ankyrin in the cerebellum by light and electron microscopy. White matter (myelinated fiber tracts) did not contain ankyrin. Granule cell bodies and axons contained ankyrin which extended into the parallel fibers and their synapses. Purkinje cells contained a nearly uniform plasma membrane undercoating of ankyrin in the cell body. However, in both of these cell types ankyrin was not detected in dendrites. Basket and stellate cells did not contain detectable ankyrin. Golgi neuroepithelial cell bodies and processes contained ankyrin while myelin and myelinated axons did not. These results indicate that the membrane skeletal protein ankyrin occurs in some, but not all, neuronal and glial cell types in the cerebellum. For the neurons in which it does occur its distribution is polarized, being limited to cell bodies and axons while not occurring in dendrites. PMID- 8341419 TI - Neuropeptide co-expression in the magnocellular neurosecretory system of the female rat: evidence for differential modulation by estrogen. AB - Single- and double-immunohistochemical staining methods were used to assay the effect of estrogen on the expression of co-existing peptides in the magnocellular neurosecretory system of the female rat. It was confirmed in colchicine-treated, ovariectomized animals that immunoreactive corticotropin-releasing factor and cholecystokinin co-exist in subsets of oxytocinergic neurons; in addition, dynorphin immunoreactivity was detected in a substantial majority of oxytocin containing magnocellular neurons. Consistent with previous studies, magnocellular vasopressinergic cells were found to display angiotensin II-, dynorphin- and galanin-immunoreactivities. Comparable results occurred in colchicine-treated ovariectomized rats independent of whether or not the animals received replacement injections of estradiol benzoate or vehicle. Ovariectomized rats that were not pretreated with colchicine showed enhanced staining (increased cell number and staining intensity of both cell bodies and terminals in the posterior pituitary) for each of the peptides that was found to co-exist in vasopressinergic neurons after treatment with estradiol; staining for vasopressin was similar in steroid- and oil-treated animals. Perikaryal staining for peptides co-localized with oxytocin was not discernibly different in estradiol- vs vehicle treated animals, while in the posterior lobe, differential effects of hormone replacement on oxytocin, cholecystokinin, and corticotropin-releasing factor immunostaining of terminals were apparent. Perikaryal staining for co-existing peptides in gonadally intact animals killed at the estrus or the diestrus II phases of the estrous cycle provided a pattern of results compatible with those seen in ovariectomized animals treated with estradiol or oil, respectively. These observations suggest that circulating gonadal steroids affect co-existing peptide expression differentially in oxytocinergic vs vasopressinergic neurons. All peptides examined that could be co-localized in vasopressinergic cells showed evidence of enhanced expression in the presence of estrogen, while at least two of these co-localized with oxytocin appeared driven in the opposite direction. The results in normally cycling rats indicate that this kind of influence may be manifest under normal physiological conditions. PMID- 8341421 TI - Synaptic contacts of serotonin-like immunoreactive and 5,7-dihydroxytryptamine accumulating neurons in the anuran retina. AB - The synapses of serotonin-like immunoreactive retinal neurons were studied in Bufo marinus and Xenopus laevis and those of 5,7-dihydroxytryptamine-labelled cells in Xenopus. Immunoreactivity to serotonin was mostly confined to amacrine cells. Synapses formed by profiles of labelled cells were almost uniformly distributed in the inner plexiform layer in both species. Interamacrine synapses were the most frequent, and in some cases two labelled amacrine cell profiles made a gap junction. Some of the labelled amacrine cells synapsed on to presumed ganglion cell dendrites and onto bipolar cell terminals. Labelled bipolar cell terminals synapsed on to non-labelled amacrine cell dendrites and received inputs both from labelled and non-labelled amacrine cells. Labelled bipolar cell profiles were not observed in the outer plexiform layer. After preloading and photoconversion of 5,7-dihydroxytryptamine in the Xenopus retina, labelled bipolar cell dendrites in the outer plexiform layer were observed to be postsynaptic to cone pedicles and less frequently to rods and horizontal cells. In the inner plexiform layer, synapse types formed by labelled bipolar cells were similar to those with serotonin immunoreactivity. The frequency of synapses formed by 5,7-dihydroxytryptamine-labelled amacrine cells increased, compared with serotonin immunocytochemistry. Labelled amacrine cells synapsed mostly with non-labelled amacrine cells, although the ratio of contacts formed by two labelled profiles increased. Synapses from labelled amacrine cell dendrites to non-labelled bipolar cell terminals and from non-labelled bipolar cell terminals to labelled amacrine cell profiles increased in number, while those from labelled amacrine cells to presumed ganglion cell dendrites decreased. The quantitative data obtained by the two approaches enabled us to propose different neuronal circuits for serotonin-synthesizing and -accumulating neurons of the Xenopus retina. PMID- 8341422 TI - The low molecular weight form of microtubule-associated protein 2 is transported into both axons and dendrites. AB - In the developing brain microtubule-associated protein MAP2 occurs as both a high molecular weight form, MAP2b, which is present only in dendrites, and a low molecular weight form, MAP2c, which is also present in axons. Because the MAP2c amino acid sequence is entirely contained within that of MAP2b it is not possible to raise a MAP2c-specific antibody, so that it has been impossible to determine whether MAP2c is present in dendrites along with MAP2b. To answer this question we have generated a MAP2c cDNA clone tagged with a 10 amino acid epitope from human c-myc. This additional sequence does not alter either the binding of MAP2c to microtubules or its effects on microtubules in non-neuronal cells. When expressed in cultured primary neurons by transfection, the myc tag allowed the distribution of MAP2c to be determined independently of endogenous MAP2 protein by immunostaining with an anti-myc antibody. This showed that MAP2c is present in all processes, indicating that it can enter all kinds of processes and is stable in their cytoplasm. The results further suggest that the selective association of high molecular weight MAP2 with dendrites depends on a mechanism that prevents either its entrance or survival in the axonal compartment. PMID- 8341424 TI - Adrenalectomy attenuates kainic acid-elicited increases of messenger RNAs for neurotrophins and their receptors in the rat brain. AB - Treatment with excitotoxin kainic acid is known to increase the level of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor in the brain. In this study we have used quantitative in situ hybridization to analyse the effect of glucocorticoids on kainic acid-induced increase of nerve growth factor and brain-derived neurotrophic factor messenger RNA in the rat brain. In adrenalectomized animals, the kainic acid-mediated increase of brain derived neurotrophic factor messenger RNA in the hippocampus and the cerebral cortex was reduced by 50% compared to sham-operated animals. The increase of nerve growth factor messenger RNA elicited by kainic acid in the dentate gyrus was almost completely abolished in adrenalectomized animals. No significant change was seen in c-fos messenger RNA in the hippocampus of adrenalectomized rat after kainic acid injection compared to sham-operated kainic acid-treated rats, while a three-fold reduction was seen in the cerebral cortex. Dexamethasone injection prior to kainic acid administration potentiated the kainic acid-induced increase of nerve growth factor messenger RNA in the dentate gyrus and the piriform cortex. In contrast, dexamethasone pretreatment did not potentiate the kainic acid-mediated increase of brain-derived neurotrophic factor messenger RNA. We also examined the effect of adrenalectomy and kainic acid injection on tropomyosin receptor kinase B and C messenger RNA, encoding essential components of high-affinity receptor for brain-derived neurotrophic factor/neurotrophin-4 and neurotrophin-3, respectively. Following adrenalectomy no change of tropomyosin receptor kinase B or C messenger RNA was detected in any of the brain regions studied compared to sham-operated animals. The injection of kainic acid caused four-fold and two-fold increases of tropomyosin receptor kinase B messenger RNA in the dentate gyrus and cerebral cortex, respectively, but no change in tropomyosin receptor kinase C messenger RNA in any of these regions. In adrenalectomized animals receiving kainic acid, the level of tropomyosin receptor kinase B messenger RNA was decreased both in the dentate gyrus and cerebral cortex as compared to sham animals treated with kainic acid. Taken together, the data suggest that excitotoxins and glucocorticoids both influence expression of brain-derived neurotrophic factor and nerve growth factor messenger RNA in the brain, but by two different mechanisms, where the effect of excitotoxin-evoked seizures is modulated by glucocorticoids. PMID- 8341423 TI - Transforming growth factor beta 1 and fibronectin messenger RNA in rat brain: responses to injury and cell-type localization. AB - Transforming growth factor-beta 1 rapidly increases in adult rat brain in response to experimental lesions. This study characterized the schedule of changes, regional distribution, and cellular localization of striatal transforming growth factor-beta 1 messenger RNA and fibronectin messenger RNA following partial striatal deafferentation by frontal cortex ablation. Frontal cortex ablation induced striatal transforming growth factor-beta 1 messenger RNA elevations that coincided temporally and overlapped anatomically with the course of degeneration of cortico-striatal afferent fibers. Within three days post lesioning, transforming growth factor-beta 1 messenger RNA was localized at the cortical wound. By 10 days, the anatomical site of transforming growth factor beta 1 messenger RNA expression shifted to the dorsal half of the deafferented striatum and co-localized with OX-42+ immunostained microglia-macrophage at the site of degenerating afferent terminals. Similarly, fibronectin messenger RNA also shifted from the cortical wound to the deafferented striatum by 10 days post lesioning. Fibronectin messenger RNA was localized to glial fibrillary acidic protein+ immunostained astrocytes surrounding degenerating corticostriatal afferents. Infusion of transforming growth factor-beta 1 peptide elevated striatal and cortical fibronectin messenger RNA. These findings suggest that microglia-macrophage associated with degenerating afferent fibres can upregulate transforming growth factor-beta 1 messenger RNA and may influence fibronectin messenger RNA synthesis in reactive astrocytes. This study suggests that transforming growth factor-beta 1 has a role in controlling extracellular matrix synthesis following brain injury, which is analogous to that in peripheral wound healing. PMID- 8341425 TI - Distribution of secretoneurin, a peptide derived from secretogranin II, in rat brain: an immunocytochemical and radioimmunological study. AB - The distribution of secretoneurin, a peptide derived from its precursor secretogranin II by proteolytic processing, was studied in the central nervous system of the rat by immunocytochemistry and radioimmunoassay and compared to the distribution of secretogranin II messenger RNA by using in situ hybridization. With a specific antiserum a distinct staining of fibers and to a lesser extent also of perikarya was observed throughout the central nervous system. A high density of immunoreactive fibers and terminals was found in several brain areas, i.e. the lateral septum, the medial parts of the amygdala, some medial thalamic nuclei, the hypothalamus, habenula, nucleus interpeduncularis, locus coeruleus, nucleus tractus solitarii, the substantiae gelatinosae of the caudal trigeminal nucleus and of the spinal cord. The quantitative distribution as measured by a radioimmunoassay agreed well with the varying densities of immunoreactivity found by immunocytochemistry. The highest concentrations of this peptide were present in the hypothalamus, in particular, in the median eminence and are comparable to those of the most highly concentrated neuropeptides. The distribution of immunopositive perikarya corresponded well with that of secretogranin II messenger RNA obtained by in situ hybridization. The pattern of secretoneurin expression in rat brain was widespread and unique, partially overlapping with established chemical transmitters and neuropeptides. The functional significance of this new brain peptide remains to be established. PMID- 8341426 TI - Sensory integration by the dorsal spinocerebellar tract circuitry. AB - Monosynaptic connections from sensory receptors to the dorsal spinocerebellar tract are believed to have a significant role in the transmission of sensory information to the cerebellum. However, predominant polysynaptic connections with highly convergent afferent input suggest a functional organization based on integrated sensory representations. We explored this possibility by examining the responses of dorsal spinocerebellar tract neurons to inputs from muscle receptors. We compared results from two sets of experiments designed to activate receptors in the gastrocnemius-soleus muscles. In one set (135 cells) we stimulated muscle receptors by stretching the isolated muscles and in the other set (194 cells) the muscle receptors were activated by passive foot flexion, which concurrently activated cutaneous and joint receptors as well. Population responses of the spinocerebellar neurons were quite different for the two types of stimuli. Foot flexion elicited long-latency excitatory responses in a majority (53%) of the cells, while muscle stretch elicited a large fraction of early peaking excitatory responses (28%) and inhibitory responses (38%). The long latency responses to flexion could not be accounted for by specific cutaneous inputs or by possible delayed reflex contractions. We concluded that both types of population response resulted from the muscle stretch and therefore the responses of dorsal spinocerebellar tract cells to these stimuli do not simply reflect the activity in specific classes of sensory receptors. PMID- 8341428 TI - Perinatal and adult factors responsible for the sexually dimorphic calcitonin gene-related peptide-containing cell population in the rat preoptic area. AB - Neurons containing calcitonin gene-related peptide in the medial preoptic nucleus exhibit the largest neurochemically defined sex difference in the rat preoptic area with a 20-fold difference in cell numbers. The gonadal steroid hormones responsible for this sexual dimorphism have been investigated by examining calcitonin gene-related peptide immunoreactivity in the preoptic area of adult rats receiving a variety of perinatal and adult gonadal steroid manipulations. Cells immunoreactive for calcitonin gene-related peptide were examined in two populations within the preoptic area, one in its ventrolateral aspect and the other located in the lateral division of the medial preoptic nucleus. Cell profile counts estimate numbers of calcitonin gene-related peptide-containing cells in the medial preoptic nucleus of the female to be 22.2 +/- 3.0 cells/section compared with 1.0 +/- 0.2 in the male (P < 0.01). No sex differences existed in the preoptic ventrolateral population of calcitonin gene related peptide cells (males 4.3 +/- 0.2, females 4.4 +/- 0.6 cells/section). Gonadectomy of male rats on postnatal day 2 resulted in the appearance of a calcitonin gene-related peptide-containing cell population in the medial preoptic nucleus which was indistinguishable from intact female rats (19.3 +/- 2.2 cells/section). Gonadectomy of adult male rats resulted in a modest increase in calcitonin gene-related peptide cell numbers within the medial preoptic nucleus (8.8 +/- 0.4 cells/section) and this was fully reversed by replacement of testosterone (0.7 +/- 0.2 cells/section).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341427 TI - Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling. AB - The nervous system may be actively involved in bone repair and in remodelling of callous tissue in bone fractures, as well as in the regulation of nociceptive impulses from the site of the trauma. The aim of this study was to assess the distribution and nature of the periosteal innervation of normal control bone and during bone healing subsequent to fracture of rat tibiae at seven, 14 and 21 days after experimental fracture using immunocytochemistry and image analysis quantification of the neuronal marker protein gene product 9.5 and sensory neuropeptide calcitonin gene-related peptide. At seven days, periosteal protein gene product 9.5- and calcitonin gene-related peptide-immunoreactive fibres showed dense ramifications and terminal sprouting. In addition to periosteum, the nerve fibres were found in the middle of the callus interspersed with inflammatory cells and penetrating into secondary minor fractures. At days 14 and 21 many tortuous nerves were found in the periosteum but not in mid callus. Image analysis quantification revealed a uniform increased proliferation of nerves after seven days. At 21 days, the intercept countings showed in excess of a three fold increase of calcitonin gene-related peptide-immunoreactive nerve fibres compared with the normal control group (P > or = 0.0001) and were almost as numerous as protein gene product 9.5-immunoreactive fibres (P < 0.005). It is postulated that calcitonin gene-related peptide-containing sensory innervation may have a potential importance in the fracture vascular control, angiogenesis and osteogenesis in addition to a protective role against excessive fracture movement. The results are consistent with the neural involvement in bone growth and remodelling. PMID- 8341429 TI - Health risks associated with mercury from dental amalgams. PMID- 8341430 TI - The incidence, benefits and variables associated with breastfeeding: implications for practice. AB - The health, nutritional and psychological benefits of breastfeeding are widely acknowledged. Breastfeeding is the recommended infant-feeding method for the first four to six months of life. Despite the well-documented benefits of breastfeeding, researchers in the United States have noted a decline in its incidence and duration over the last several years. In order to address this decline, clinicians need to be familiar with what is currently known about breastfeeding trends and benefits, as well as variables associated with infant feeding choices and reasons for premature weaning. Current breastfeeding research and implications for nursing practice are the focus of this article. Specifically, health practitioners are encouraged to develop a prolactation protocol for their practice. This involves development and/or utilization of educational and support services that span the prenatal period and continue until the child is weaned. PMID- 8341431 TI - Assessment and management of galactorrhea. AB - Galactorrhea, inappropriate lactation, is a relatively common clinical sign encountered by primary health care providers. However, this physical sign is not synonymous with life-threatening breast or intracranial malignancy; rather, it may be physiologic, drug-induced or idiopathic. Given the 20 percent prevalence of pituitary adenomas in women with galactorrhea, the primary health care provider must rule out, in every case, intracranial causes for galactorrhea. This article reviews relevant physiopathology and develops an assessment and diagnostic protocol, which includes indications for urgent referral. It concludes with summaries of treatment modalities, outlining the role of the primary care provider throughout the diagnostic and treatment processes. PMID- 8341432 TI - Management strategies for promoting successful breastfeeding. AB - Clinicians can promote a successful breastfeeding experience by providing support, anticipatory guidance and practical information. This article presents the components of early follow-up and guidelines for assessment. Management strategies for common problems are discussed, such as nipple soreness, cracked nipples, plugged ducts and mastitis, insufficient infant weight gain, perceived inadequacy of milk supply, breast-milk jaundice, sexual adjustment and failure at breastfeeding. Breastfeeding guidelines for employed mothers and adoptive mothers are indicated. PMID- 8341433 TI - The delivery of Early and Periodic Screening, Diagnosis and Treatment Program services by NPs in a nursing center. AB - Enacted in 1967 as a required component of the Medicaid program, the Early and Periodic Screening, Diagnosis and Treatment Program combines outreach, health screening, follow-up care for detected conditions, and case management. This article describes the delivery of this program's services by nurse practitioners in an academic nursing center. Detailed are the Nursing Center's activities to develop a services contract for the Early and Periodic Screening, Diagnosis and Treatment Program and to improve client access. Issues discussed include protocol development, prescriptive authority and referral to health care providers accepting Medicaid. Services are evaluated by auditors, faculty, students and clients. The article concludes with suggestions for other providers or potential providers of the program. PMID- 8341434 TI - Three (or four?) options for doctors. PMID- 8341435 TI - Draconian powers in Health Commissioner Bill. PMID- 8341436 TI - Public health spending is down. PMID- 8341437 TI - Mortality and social class in Maori and nonMaori New Zealand men: changes between 1975-7 and 1985-7. AB - AIMS: Social class mortality differences in Maori and nonMaori New Zealand men aged 15-64 years have previously been examined for the period 1975-7. The analysis has now been repeated for the period 1985-7 in order to examine changes over time. METHODS: Numerator data were obtained from national death registrations and denominator data were obtained from the 1976 and 1986 censuses. These were used to calculate age-standardized death rates in Maori and nonMaori. RESULTS: Mortality declined by 28% in Maori and 14% in nonMaori between 1975-7 and 1985-7. The death rate for diseases amenable to medical intervention fell by 54% in Maori and 23% in nonMaori, but the Maori death rate was still 2.8 times the nonMaori death rate, whereas the relative risk for nonamenable causes was only 1.4. CONCLUSIONS: Some progress has been achieved in reducing ethnic differences in mortality in New Zealand men, but substantial differences remain for diseases which are amenable to medical intervention (including chronic rheumatic heart disease, hypertensive heart disease, and tuberculosis). It is likely that these differences reflect poor access to culturally safe and appropriate health care in Maori people. PMID- 8341438 TI - New coronary intervention devices: needed skills or useless frills. PMID- 8341439 TI - Mometasone versus betamethasone creams: a trial in dermatoses. AB - AIM: To compare the efficacy and safety of mometasone furoate cream 0.1% applied daily versus betamethasone valerate cream 0.1% applied twice daily in a variety of dermatoses. METHODS: A 4 week study was undertaken of patients with at least moderately severe dermatoses as judged by scoring of a target lesion. Weekly global improvement was assessed, as well as change in target lesion scores. Local side effects were noted including observation of atrophy. RESULTS: Fifty eight patients in three centres completed the study, 30 in the betamethasone group and 28 in the mometasone. There was no difference in demographic variables or disease severity in each group or any difference between the three investigator gradings of initial severity. There was a rapid onset of improvement in both groups by day seven (scores being reduced by 72% in the betamethasone group and 65% in the mometasone group). By the fourth week visit there was 90% reduction in the betamethasone group score and 93% in the mometasone. There was no significant difference between the groups. CONCLUSION: Mometasone furoate cream 0.1% applied daily in dermatoses is as effective as betamethasone valerate 0.1% cream. Both creams had rapid onset of action and had no signs of atrophy. Better patient compliance could be expected with the convenience of mometasone cream being applied daily. PMID- 8341440 TI - Parental perceptions of information about medication prescribed for their children. AB - AIMS: The study aimed to examine parents' perceptions of the information provided to them on prescribed medication; how it might be improved and; parental level of knowledge of medication administration. METHODS: 245 parents completed a questionnaire at a preschool health day. The questionnaire covered parental opinion on whether the doctor provided enough information about illness and medication, recall of pharmacist's instructions on medication, parental general knowledge of medication and what parents wanted to know about medication for their children. RESULTS: The findings indicated there was an overall lack of information from the doctor on side effects and what to do if problems occurred with medication. Furthermore, half (49%) of the parents did not recall receiving any information from the pharmacist. Parents appeared to understand the basics of medication administration. CONCLUSIONS: It is suggested that improvements should be made regarding the information given to parents on prescribed medication. This may improve satisfaction with the service received from health professionals, such as doctors and pharmacists, and increase patient compliance with treatment regimes. PMID- 8341442 TI - NZMA dissent. PMID- 8341441 TI - Drug treatment of depression. PMID- 8341443 TI - Side effects of acipimox (Olbetam) PMID- 8341444 TI - The patient with haematuria. PMID- 8341445 TI - Chronic fatigue syndrome. PMID- 8341446 TI - A need for critical analysis, not confused criticism. PMID- 8341447 TI - Medical Council defends its questions. PMID- 8341448 TI - Ethics in the new environment. PMID- 8341449 TI - Computer column: patient numbering v privacy. PMID- 8341450 TI - Measuring quality. PMID- 8341451 TI - Transcatheter closure of patent ductus arteriosus in children and adults. AB - AIM: To describe the initial New Zealand experience of transcatheter patent ductus arteriosus closure in adults and children. METHODS: Twenty-three children beyond infancy and four adults with isolated patent ductus arteriosus were selected for transcatheter umbrella closure. Rashkind umbrellas were placed across the patent ductus arteriosus through a percutaneously inserted long venous sheath using the Mullins technique. RESULTS: In 25 of the 27 patients a Rashkind umbrella was placed accurately. In two patients the umbrella could not be placed accurately: in one the procedure was abandoned uneventfully and in one the umbrella embolised to the right pulmonary artery necessitating surgical removal of the device and patent ductus arteriosus closure. There were no other significant complications. A second umbrella insertion is planned in two children for a significant residual leak at 1-year follow up. CONCLUSIONS: Transcatheter patent ductus arteriosus closure is a low risk and usually effective alternative to surgical closure for the majority of patients beyond infancy. PMID- 8341453 TI - Prescription for increasing cooperation between clinicians and managers in public hospitals. PMID- 8341452 TI - Neuropsychological impairment and return to work following severe closed head injury: implications for clinical management. AB - AIMS: To study the rate and timing of return to work following severe closed head injury, and to compare the neuropsychological functioning of patients who successfully return to work with that of patients who fail to return to work. METHODS: The vocational status, level of cognitive functioning and personality functioning of a consecutive series of 66 patients who survived severe closed head injury was assessed between six months and three years postinjury. The level of cognitive and personality functioning of patients who returned to work were compared with that of patients who failed to return to work. RESULTS: Twenty five percent of patients failed to return to work, and a further 17% returned to work under special conditions of employment. Failure to return to work was related to the degree of neuropsychological impairment (cognitive deficit and adverse personality change), injury severity (duration of posttraumatic amnesia), and age. Multiple regression analysis found the total number of neuropsychological symptoms to be the strongest predictor of the patients' return to work. CONCLUSIONS: These findings suggest that neuropsychological symptoms are the main mechanism through which severe brain injury affects the ability to return to work. It is recommended that vocational rehabilitation of severe closed head injury patients be based on a comprehensive neuropsychological assessment. PMID- 8341454 TI - Demographic variables in Auckland medical students. AB - AIMS: To review the important background details of students admitted to the Auckland School of Medicine over its 25 years. METHODS: Data collected at the time of application on 2448 students who successfully gained entry to the course has been analysed and compared with similar demographic variables in the New Zealand population as a whole, and with some of the findings from a survey performed on the total student population enrolling at Auckland University during 1990. RESULTS: Successful applicants had a mean age of 18.6 years, 39.7% were females and 77% were born in New Zealand. Eighty-three percent were European, 3.6% Maori, 2.4% Pacific Islanders and 10.8% Chinese, Indian or other Asian. Sixty-three percent came from cities over 100,000, 16% being from towns less than 20,000 people. State schools were attended by 77% of entrants and 55% went to single sex schools. University students enrolling in 1990 came from affluent backgrounds with 70% of medical students that year being from socioeconomic levels one and two. Parental occupation was found to clearly influence the career choice of students. CONCLUSIONS: Auckland medical students are predominantly from large cities and affluent backgrounds with only those of European origin being admitted in the same proportion as they occupy in the New Zealand population. The high ratio of Asian students reflects their commitment to senior secondary school studies while the lower admission rate for Maori and Polynesian students is due in part to the large number who leave school without completing their secondary education. The possible impact of these demographic variables on recruitment and loss from the course and on the choice and location of practice is discussed. PMID- 8341455 TI - Primary nonHodgkins lymphoma of kidney with humoral hypercalcaemia: case report. PMID- 8341456 TI - Establishment of a registry for hereditary nonpolyposis colorectal cancer in New Zealand. PMID- 8341457 TI - Therapeutic recommendations for common sexually transmitted diseases; Part 2. PMID- 8341458 TI - Resource constraints--what do we tell our patients? PMID- 8341459 TI - The Health Research Council and diabetes mellitus prevention. PMID- 8341460 TI - Failure of scabies treatment. PMID- 8341461 TI - Nonfluoridation in Oamaru and Timaru. PMID- 8341462 TI - Pharmaceutical company sponsorship. PMID- 8341463 TI - Antenatal self care. PMID- 8341465 TI - Hormone replacement therapy. PMID- 8341464 TI - Computerised age-sex registers. PMID- 8341466 TI - Serum methadone concentrations. PMID- 8341467 TI - Maternity benefits: the continuing saga. PMID- 8341468 TI - Core health services--a fiction? PMID- 8341469 TI - Minister says HUHC review unlikely. PMID- 8341470 TI - Unlinked anonymous monitoring of HIV prevalence at sexually transmitted disease clinics. AB - AIM: To determine the prevalence of HIV infection among patients attending the four sexually transmitted disease (STD) clinics in two metropolitan areas of New Zealand. METHODS: The population studied comprised everyone who attended between August 1991 and August 1992 because of concern about a possible new episode of an STD and who had a blood specimen taken for hepatitis B (or syphilis) serology. The study involved unlinked anonymous testing of left-over blood specimens, following ethical guidelines that have been proposed internationally. RESULTS: Among 8478 specimens tested, 23 (2.7 per 1000) were found to be HIV positive. The seroprevalence rates per 1000 among women, heterosexual men, and homosexual or bisexual men were 1.1, 1.3, and 44, respectively. All but five of the infected people were either known to be HIV positive or had an identifiable test during their clinic attendance. CONCLUSIONS: The seroprevalence rates are similar to those reported from STD clinics in England, and suggest that heterosexual transmission of HIV infection has not yet been extensive in New Zealand. PMID- 8341471 TI - Male cancer mortality by occupation: 1973-86. AB - AIM: To identify male occupational groups with increased risk of death from cancer in 1973-86. METHOD: Age and social class standardised mortality ratios were calculated for males 15-64 years for all cancers combined and for site specific cancers by occupational group. RESULTS: In general, higher socio economic groups had a lower all cancer mortality and lower socio-economic groups a higher mortality. After standardisation for age and social class, mortality ratios were increased for lung cancer in bricklayers and carpenters (SMR = 125; 95% CI: 110-141), machine tool operators (SMR = 218; 95% CI: 131-342), and welders (SMR = 140; 95% CI: 120-161), with the first group also having an increased risk for pleural mesothelioma (SMR = 222; 95% CI: 70-522). Malignant melanoma risk was increased in clerical workers (SMR = 147; 95% CI: 106-199) and not in outdoor occupations. Colon cancer mortality risk was increased in managers (SMR = 125; 95% CI: 104-148), and woodworkers (SMR = 147; 95% CI: 115-186). Stomach cancer mortality risk was raised for machine tool operators (SMR = 357; 95% CI: 128-782). Painters had an increased ratio for multiple myeloma (SMR = 352; 95% CI: 140-729) and machine tool operators an increase for leukaemia (SMR = 172; 95% CI: 45-446). CONCLUSIONS: The use of routinely collected data to examine cancer mortality by occupation is a useful method to identify groups with increased risks and provide information for hypothesis generation. Further research may be warranted to investigate lung and digestive cancers in woodworkers and machine tool operators, and cancer of the haemopoietic and lymphatic systems in painters and machine tool operators. PMID- 8341472 TI - Informed consent. PMID- 8341473 TI - Hepatitis C virus infections in oral and injectable drug users. AB - AIM: To assess the frequency of hepatitis C virus antibodies (anti HCV) and exposure to hepatitis B virus in injectable and oral drug users in Auckland. METHODS: Sera from 110 injectable drug users and 154 oral drug users were tested for anti HCV as well as hepatitis B and D virus markers. Liver function tests were also performed. RESULTS: 73% of injectable drug using persons and 4% of oral drug using persons were positive for anti HCV. Over half of persons with a positive anti HCV result had an abnormal elevation of the liver enzyme alanine aminotransferase (ALT). Total HBV exposure was similar in both injectable drug user and oral drug user groups at approximately 30%, with little difference between ethnic groups. There were no positive results for hepatitis D virus infection. CONCLUSIONS: Injectable drug users who are anti HCV positive may represent a potential source of HCV infection in the community. An upgraded educational programme, perhaps in conjunction with the needle/syringe exchange programme, may be required to ensure drug users are aware of the risks of HCV infection to both themselves and the community. PMID- 8341474 TI - An analysis of unscheduled return visits to an urban emergency department. AB - AIM: This study was undertaken to identify the reasons for unscheduled return visits to an urban emergency department, particularly those relating to physician errors in diagnosis and management, and, where possible, to identify strategies to reduce unscheduled return visits. METHOD: All patients returning to the Emergency Department, Christchurch Hospital, within seven calendar days of initial visit were identified. These cases were reviewed to identify reasons for return visit. RESULTS: Unscheduled return visits accounted for 2% of patient encounters. Sixty one per cent were due to illness related factors, 27% to patient related factors, 11% to physician related factors and 1% to system related factors. Significant management errors occurred in nine patients (4.4% of unscheduled return visits), three of whom were admitted. There were no ICU or CCU admissions and no deaths. CONCLUSIONS: Significant physician errors were a minor reason for reattendance at the emergency department and no specific areas of deficiency were identified. These might be further reduced by increasing the seniority and experience of staff and by the introduction of regular audit, continuing medical education and vocational training programmes. Interventions to reduce patient related unscheduled return visits might include better explanation of the role of the emergency department and better communication with patients about their illness and treatment. PMID- 8341475 TI - Trial of an asthma action plan in the Maori community of the Wairarapa. AB - AIMS: An asthma action plan has been tested in a study conducted by Wairarapa Maori community health workers and the Wellington asthma research group. There were several distinctive features of the project, including the programme of marae-based asthma clinics, and the partnership between the researchers and the Maori community groups. This paper describes the process by which the study was conducted since this experience may be relevant to future Maori health research projects. METHODS: The programme was launched with a series of hui at marae in the Wairarapa, and marae-based clinics were set up. These were followed up by further support from the Maori community health workers who helped people to keep diaries to monitor their asthma, and generally maintained contact. The severity of asthma in the participants was compared for a two-month period before the action plan was introduced, and for a four-month period after the plan was introduced. RESULTS: There was a high participation rate, with 91% (63/69) of participants finishing the programme, 75% of whom adequately completed their daily asthma diaries. Asthma control improved significantly in the participants. They commented positively on the programme, and particularly on the marae-based clinics. CONCLUSIONS: The study was successful in terms of participation in the marae-based clinics, acceptance and use of the plan, and improvement in asthma control of the participants. The findings indicate what can be achieved when researchers and Maori community groups work in partnership. PMID- 8341477 TI - Hypercalcaemia of malignancy. PMID- 8341476 TI - Use of hormonal contraceptives in an institutional setting: reasons for use, consent and safety in women with psychiatric and intellectual disabilities. AB - AIM: To describe the use of hormonal contraceptives in institutionalised women with psychiatric and/or intellectual disabilities. METHODS: Women who had been disability or mental health service inpatients for six months or more and were prescribed hormonal contraceptives were included. Data were collected from their clinical files and from structured interviews of the women and of their primary care givers. RESULTS: Forty two women were prescribed contraceptives, of whom 23 were intellectually disabled and 28 had mental illnesses. Most women had no children; four had had one child and two, two children. Thirteen were not sexually active. Depot medroxyprogesterone acetate (Depo Provera) was prescribed for 69%, combined oral contraceptive agents for 14% and progestin-only oral contraceptives for 17%. Contraceptives were initially prescribed by hospital staff for all but 1 woman, and were administered without consent for over half the group, including 11 women for whom this administration was not legally authorized. Less than half the group had blood pressure measured within the previous 12 months and only a third had a cervical smear within the previous 3 years. Of the women who were sexually active, less than half knew how to protect themselves from sexually transmitted diseases and less than 10% regularly used condoms. CONCLUSIONS: Improvements in reproductive health care for these women are needed, in particular attention to education and client participation in decisions about contraceptive treatment. It is suggested that gynaecological and family planning services be provided separately from psychiatric services. PMID- 8341478 TI - Health provisions for the elderly. PMID- 8341479 TI - Fluoridation. PMID- 8341480 TI - Fluoridation. PMID- 8341481 TI - The relevance of gluten in pharmaceutical products. PMID- 8341482 TI - Cannabis use among New Zealand adolescents. PMID- 8341484 TI - Munchausen syndrome by proxy. PMID- 8341485 TI - Blood transfusion trust. PMID- 8341483 TI - Occupational overuse syndrome (OOS) PMID- 8341486 TI - Medical milestone. PMID- 8341487 TI - Botulinum treatment of congenital esotropia. PMID- 8341488 TI - Cardiovascular risk factors and ARM. PMID- 8341489 TI - Cardiovascular risk factors and ARM. PMID- 8341490 TI - Why payment settings can influence practice guidelines. PMID- 8341491 TI - Glycemic control and development of retinopathy in youth-onset insulin-dependent diabetes mellitus. Results of a 12-year longitudinal study. AB - BACKGROUND: In 1979, the authors began a prospective study of the natural history of retinopathy in youth-onset insulin-dependent diabetes mellitus (IDDM). Their major goal was to determine if there was an association between glycemic control and the development and progression of retinopathy. METHODS: The study consisted of 420 individuals with IDDM (onset younger than 20 years of age) and no retinopathy at baseline. Study subjects were enrolled between 1979 and 1988. Stereo color fundus photographs were obtained annually. Two eye endpoints were recorded: duration when retinopathy was first detected, and when proliferative retinopathy was detected. Glycemic control was assessed by quarterly determinations of glycohemoglobin (GHb). Life-table analyses were performed relating duration of diabetes, sex, GHb, and age of diabetes onset to development of retinopathy. RESULTS: Retinopathy did not develop before 2 years' duration or before puberty. The prevalence of retinopathy was 50% by 9 years' duration and 100% by 20 years' duration. Retinopathy developed in females approximately 2 years sooner than in males, but plotting duration as postpubertal years resulted in nearly identical rates. Retinopathy developed significantly earlier in subjects with prepubertal onset of diabetes than in subjects with postpubertal onset if duration was plotted as postpubertal years. When separated into three groups based on GHb levels (< 7.5%, 7.5%-9%, > 9%), retinopathy developed approximately 2 years later in subjects in the less than 7.5% GHb group than those in the higher GHb groups. Proliferative retinopathy developed in 11 subjects. Their mean GHb level was higher than the mean GHb for those without proliferative retinopathy (10.9 versus 8.6%; P < 0.01). The higher the level of GHb, the sooner proliferative changes were detected. CONCLUSION: Long-term glycemic control is significantly related to both development and progression of retinopathy. Prepubertal duration of diabetes is a significant risk factor for the development of retinopathy. PMID- 8341492 TI - Factors influencing the onset and progression of diabetic retinopathy in subjects with insulin-dependent diabetes mellitus. AB - BACKGROUND: The etiology of diabetic retinopathy is poorly understood. In the current study, factor associated with the onset and the progression or regression of retinopathy are evaluated. METHODS: Two hundred seventy-seven subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were evaluated longitudinally for retinal changes over a mean of 2.7 years. The multistate Markov model was used to analyze the influences of the duration of diabetes, a family history of hypertension, age, sex, cigarette smoking, systolic blood pressure, diastolic blood pressure, cholesterol levels, and longitudinal glycohemoglobin (GHb) values on the development and the progression or regression of retinopathy. RESULTS: Univariate analysis confirmed that four factors were significantly associated with the etiology and the progression or regression of diabetic retinopathy: age, duration of diabetes, mean longitudinal GHb levels (all at P < 0.01), and diastolic blood pressure (P < 0.04). However, age was no longer significant when controlled by duration of diabetes. Cigarette smoking was only associated significantly with background retinopathy (stages 2 and 3). Systolic blood pressure, sex, a family history of hypertension, and cholesterol levels were not significantly associated with retinopathy. CONCLUSIONS: The onset of diabetic retinopathy is associated with the duration of diabetes, mean longitudinal GHb levels, smoking, and diastolic blood pressure. A longer duration of diabetes, higher GHb values, and higher diastolic blood pressure levels are associated with an increased risk of progression and a decreased chance of regression of diabetic retinopathy. PMID- 8341493 TI - Is gross proteinuria a risk factor for the incidence of proliferative diabetic retinopathy? AB - PURPOSE: To examine the relationship between gross proteinuria, measured at the initial examination, and the 4-year incidence of proliferative diabetic retinopathy (PDR) in a population-based study in Wisconsin. METHODS: Gross proteinuria was measured by reagent strip. Diabetic retinopathy was determined from stereoscopic fundus photographs in a masked fashion using the modified Airlie House classification scheme. RESULTS: In the younger-onset group taking insulin (n = 693), the relative risk of proliferative retinopathy developing in those with gross proteinuria at baseline was 2.32 (95% confidence interval [CI]: 1.40,3.83) compared with those without gross proteinuria. For the older-onset group taking insulin, the relative risk was 2.02 (95% CI: 0.91,4.44), and for those not taking insulin it was 1.13 (95% CI: 0.15,8.50). After controlling for other risk variables, the relationship was of borderline statistical significance (P = 0.052) in the younger-onset group with no or early nonproliferative retinopathy at baseline. CONCLUSION: These data suggest that gross proteinuria is a risk indicator for proliferative retinopathy in younger-onset patients with diabetes. These patients might benefit from having regular ophthalmologic evaluation. PMID- 8341494 TI - Retinal nerve fiber layer defect as an early manifestation of diabetic retinopathy. AB - PURPOSE: An incidence of and risk factors for retinal nerve fiber layer defect were investigated in patients with type II diabetes mellitus and compared with that of age-matched control subjects. METHODS: The authors photographed the retinal nerve fiber layer of the right eye in each of 137 patients with diabetes and 144 healthy control subjects. The level of diabetic retinopathy ranged from levels 1 (no microaneurysm) to 4 (eyes with localized intra-retinal microvascular abnormalities or venous beading). Risk factors for the nerve fiber layer defect analyzed were age of patients, visual acuity, axial length, optic disc size, glycosylated hemoglobin, systolic blood pressure, and level of diabetic retinopathy. RESULTS: Defects of the retinal nerve fiber layer were found in 6/30 (20%) eyes with level 1 retinopathy, 8/14 (57%) eyes with level 2 retinopathy, 24/47 (51%) eyes with level 3 retinopathy, and 36/46 (78%) eyes with level 4 retinopathy. These defect incidences were significantly higher than that of the control group, which had 5/144 (3.5%) defects (P < or = 0.001). Risk factors for this nerve defect were level of diabetic retinopathy (P = 0.002), high systolic blood pressure (P = 0.0232), and patient's age (P = 0.0478). Not correlated with the incidence of the retinal nerve fiber layer defect were visual acuity, disc size, axial length, and glycosylated hemoglobin level at the time of examination. CONCLUSION: These findings suggest that the retinal nerve fiber layer defect is common in patients with early diabetic retinopathy. Risk factors for this defect were higher level of diabetic retinopathy, systemic hypertension, and advanced age. PMID- 8341495 TI - An evaluation of the influence of reproductive factors on the risk of metastases from uveal melanoma. AB - BACKGROUND: There is a paucity of data concerning the possible role played by hormonal factors in the risk of metastases from intraocular melanomas. METHODS: The authors studied the influence of post-diagnosis pregnancy and oral contraceptive use in a group of women of reproductive age (45 or younger) who were treated for uveal melanoma by proton beam irradiation. A baseline reproductive history had been collected before irradiation for all women, and interim reproductive data were collected by mailed questionnaire. RESULTS: In this age group, the overall rate of metastasis among women was similar to that of men treated during the same interval (adjusted rate ratio: 1.28; 95% confidence interval: 0.62-2.67). A total of 24 full-term pregnancies were reported among the 139 women still menstruating at diagnosis. Twenty-three women reported regular oral contraceptive use. Metastases developed in 15 of the 139 women. Compared with other women in the series, rates of metastases were not higher among the women who reported pregnancies (P = 0.932) or oral contraceptive use (P = 0.424) after diagnosis. CONCLUSION: Although based on limited numbers, results suggest that the hormonal environment has no appreciable influence on risk of metastases in younger women with uveal melanoma. PMID- 8341496 TI - Intraoperative fluorescein angiography. AB - BACKGROUND: Fluorescein angiography is often beneficial in the evaluation and management of many retinal vascular diseases. However, vitreous blood or opacities may prevent fluorescein studies before pars plana vitrectomy. After vitrectomy, fluorescein angiography may be delayed, creating uncertainty over differentiation of preoperative, intraoperative, and postoperative findings. METHODS: The authors have modified an intraocular light source and operating microscope to perform intraoperative fluorescein angiography easily. Twenty-five patients underwent fluorescein angiography during pars plana vitrectomy. All studies were recorded using a microscope-mounted video camera for intraoperative and postoperative evaluation. RESULTS: In all cases, intraoperative angiography was performed without complication. Indications for intraoperative studies included confirmation of macular edema, delineation of avascular retina, and localization of retinal and choroidal neovascularization. All videotape recordings of procedures were of high quality, allowing easy review and interpretation. CONCLUSION: Intraoperative fluorescein angiography is an easily performed adjunctive diagnostic procedure that can aid intraoperative evaluation and treatment of selected retinal vascular disorders. PMID- 8341497 TI - Hemodynamic alterations in the acute retinal necrosis syndrome. AB - BACKGROUND: Clinical and histopathologic observations suggest a role for ischemia in the pathogenesis of the acute retinal necrosis (ARN) syndrome. Disruption of blood flow appears to occur at some level in the retina or choroid and may account for some of the major features of the syndrome. METHODS: To investigate these potential circulatory changes, color Doppler imaging (CDI) was used to quantitate blood flow velocities and vascular resistance in the central retinal, ophthalmic, and short posterior ciliary arteries in ten consecutive patients with unilateral ARN syndrome. Data were analyzed with a paired Student's t test. The unaffected fellow eyes served as controls. RESULTS: Blood flow velocities within the central retinal artery were significantly reduced in eyes with ARN syndrome compared with control eyes. In affected eyes, there was a mean reduction of 55%, 60%, and 72% in peak systolic, average, and end-diastolic velocities, respectively (P < 0.01). The calculated vascular resistance of the central retinal artery showed an upward trend, but the data fell short of statistical significance. Blood flow velocities from the ophthalmic and short posterior ciliary arteries were not significantly different compared with controls. CONCLUSIONS: This study demonstrates marked circulatory changes in the central retinal artery of eyes involved with the ARN syndrome. Although the exact mechanism and clinical significance are yet to be determined, the data support the presence of retinal arterial hemodynamic compromise in this condition. PMID- 8341498 TI - Toxoplasmosis neuroretinitis. AB - BACKGROUND: Neuroretinitis is a distinct clinical entity consisting of moderate to severe visual loss, optic nerve head edema, macular exudate in a stellate pattern, and variable vitreous inflammation. Although the etiology is usually postviral or idiopathic, an acute infectious cause occasionally is demonstrated. METHODS: Five juvenile or young adult patients with neuroretinitis are presented with serologic evidence of Toxoplasma gondii infection. Four of the five patients were treated with systemic antibiotics and corticosteroids; one patient was not treated. RESULTS: With a mean follow-up period of 50 months, visual acuity returned to 20/25 or better in four patients, with one patient regaining visual acuity of 20/60. Two patients had one or more recurrent episodes of neuroretinitis, distinguishing toxoplasmosis from idiopathic neuroretinitis, which is usually a monophasic illness. CONCLUSION: Toxoplasmosis infection is a rare, but potentially treatable, form of neuroretinitis and should be included in the differential diagnosis of "Leber's idiopathic stellate retinopathy." PMID- 8341499 TI - The diagnostic histopathologic features of ocular malaria. AB - BACKGROUND: The ocular complications in patients with malaria have been studied clinically by many investigators, but the histopathologic changes were rarely described and generally regarded as nonspecific. METHODS: The eye of a 53-year old man who died of chloroquine-resistant Plasmodium falciparum malaria was studied by brightfield and polarized light microscopy. FINDINGS: An epibulbar hemorrhage that involved the conjunctiva, episclera, and tendinous insertion of the medial rectus muscle was present. Cytoadherence and rosetting of the parasitized erythrocytes were observed within the partially occluded lumens of small retinal and uveal blood vessels. The birefringence of hemozoin (malarial pigment) within the lumens of small ocular blood vessels and in the hemorrhagic epibulbar area was demonstrated by polarized light. CONCLUSION: Birefringent hemozoinemia in vascular lumens of ocular tissues indicates systemic malarial infestation by any of the four species of malaria. Cytoadherence and rosetting of the parasitized erythrocytes inside ocular capillaries and venules is diagnostic of P. falciparum and is an important cause of ocular hemorrhage. PMID- 8341500 TI - Retinal folds in Terson syndrome. AB - BACKGROUND: Perimacular retinal folds have been reported in the shaken baby syndrome, but have not been described in adults with Terson syndrome. METHODS: The authors present two patients with perimacular retinal folds in adults with Terson syndrome. In one patient, electron microscopy was used to examine the membrane spanning the fold. RESULTS: The membrane spanning the perimacular fold was found to be internal limiting membrane. The pathogenesis of these perimacular folds found in adults sustaining direct head trauma is probably different from that previously described for folds seen in infant eyes with shaken baby syndrome. CONCLUSION: Retinal folds occurring in Terson syndrome are clinically similar to those seen in the shaken baby syndrome. PMID- 8341501 TI - Immunocytologic findings in a case of Vogt-Koyanagi-Harada syndrome. AB - BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is a form of chronic panuveitis that often has a poor long-term visual outcome. To the authors' knowledge, there have been only two previous reports describing immunocytologic findings in the eyes of patients with VKH syndrome, all studied in relatively late stages of the disease. METHODS: The authors performed immunocytologic studies on the enucleated eyes of a patient with active VKH syndrome, using monoclonal antibodies to mononuclear subsets, major histocompatibility antigens, and viral and treponemal agents, to better understand the pathophysiologic mechanisms underlying the disease. Emulsified chorioretinal tissue also was processed for viral isolation in tissue culture and for Treponema pallidum by rabbit inoculation studies. RESULTS: The dense uveal infiltrates in active VKH syndrome are composed predominantly of T lymphocytes and HLA-DR+ macrophages. Scattered T cells and plasma cells were present in the retina. In addition, nondendritic-appearing CD1 (Leu-6) positive cells were localized in the choroid, in close proximity to choroidal melanocytes. No microbial agents were identified. CONCLUSION: Whereas the etiology of the VKH syndrome remains an enigma, the authors' immunocytologic findings are consistent with a T-cell-mediated disorder. In demonstrating CD1 (Leu-6) positive cells in the infiltrates, the authors propose a potential role for these cells in the etiology of VKH syndrome. PMID- 8341502 TI - The association of HLA-B8, B51, DR2, and multiple sclerosis in pars planitis. AB - PURPOSE: To establish a human leukocyte antigen (HLA) association in a homogeneous population of patients with pars planitis. METHODS: A strict set of inclusion parameters was established for the diagnosis of pars planitis. Forty patients with pars planitis who met these criteria underwent HLA analysis of class I and II phenotypes. RESULTS: HLA-B8 was present in 15 (37.5%) of 40 patients versus 85 (19.7%) of 431 controls (relative risk, 2.44; P = 0.011). HLA B51 was present in 9 (22.5%) of 40 patients versus 51 (11.8%) of 431 controls (relative risk, 2.16; P = 0.049). HLA-DR2 was present in 27 (67.5%) of 40 patients versus 121 (28.0%) of 431 controls (relative risk, 5.32; P < 0.0001). HLA-DR2 has been associated with multiple sclerosis (MS). Exclusion of five patients with pars planitis in whom MS subsequently developed did not change the significance of these findings. CONCLUSIONS: The strongest association of pars planitis with HLA-DR2 and the temporal development of MS in some patients with pars planitis further supports an association between pars planitis and MS. PMID- 8341503 TI - Intraocular lens implantation versus no intraocular lens implantation in patients with chronic iridocyclitis and pars planitis. A randomized prospective study. AB - PURPOSE: The authors studied the safety of intraocular lens (IOL) implantation in patients with uveitis. METHODS: The authors prospectively randomized 26 patients with chronic iridocyclitis (22 patients) or pars planitis (4 patients) to undergo IOL implantation or no IOL implantation at the time of cataract surgery. RESULTS: There was no statistical difference in visual acuity results at 1 year between the two groups. There was a trend toward better visual acuity in patients with chronic iridocyclitis without IOLs. Cocoon-like dense fibrous membranes enveloped the IOL in two patients. CONCLUSION: The authors conclude that IOLs are relatively safe in patients with chronic iridocyclitis but that only a much larger study could determine if the trend toward better visual acuity without an IOL was real. PMID- 8341504 TI - Cataract extraction in patients with pars planitis. AB - BACKGROUND: The authors analyzed the results of cataract surgery performed on patients with pars planitis from January 1985 through August 1992. METHODS: One hundred twenty-six patients with pars planitis were evaluated and treated during this period. Cataracts that warranted surgery developed in 12 patients (18 eyes) from this tertiary referral population. These 12 patients were evaluated with respect to pars planitis duration, systemic disease association, treatment regimens, macular and disc pathology, and final visual result. RESULTS: The average final visual acuity of these 18 eyes was 20/38, and 83% of the patients achieved a final visual acuity better than or equal to 20/40. The factors that limited visual recovery to this level were primarily macular and optic nerve pathology (cystoid macular edema [CME], macular epiretinal membrane, and optic atrophy). Control of inflammation required regional steroids in all patients, systemic steroids in ten patients, and immunosuppression in four patients. Posterior chamber lens implantation accompanied the surgery in 14 eyes (10 patients). Recurrent episodes of inflammation in two patients (3 eyes) resulted in accumulation of deposits on the posterior chamber intraocular lens (IOL) surface. Deposits were removed by a YAG laser lens "polishing" session. CONCLUSION: Absolute control of inflammation in patients with pars planitis through a stepladder approach may reduce the incidence of cataract development, and can certainly improve visual rehabilitation after cataract extraction. Implantation of a posterior chamber lens can be well tolerated in selected cases. PMID- 8341505 TI - Pseudophakia for traumatic cataracts in children. AB - PURPOSE: The purpose of this prospective study is to evaluate the postoperative visual acuity, refractive error, intraocular pressure, and status of the posterior capsule in children with traumatic cataracts who undergo extracapsular cataract extraction and insertion of a posterior chamber lens. METHODS: Extracapsular cataract extraction and primary endocapsular fixation of a posterior chamber lens implant were performed in eight children (age range, 4-17 years) with unilateral traumatic cataracts. RESULTS: There were no intraoperative complications, and seven of eight eyes achieved 20/40 or greater spectacle visual acuity during an average follow-up interval of 10 months (range, 5-20 months). The average postoperative spherical equivalent refractive error was +0.33 diopter (D) (range, -2.25 to +2.12 D); the average postoperative anisometropia was approximately 1 D (range, 0-2.25 D). In one patient, a coagulase-negative staphylococcal endophthalmitis developed 10 days after surgery. In three eyes that had opacified posterior capsules, YAG laser capsulotomy was performed. CONCLUSIONS: These preliminary results suggest that intraocular lens (IOL) implantation may be a safe and effective method of optical correction for children with traumatic cataracts. PMID- 8341506 TI - Epithelial interface cysts after epikeratophakia. AB - BACKGROUND: Epithelial interface cysts have been occasionally observed after lamellar keratoplasty. The authors report the incidence, clinical significance, and management of this complication in epikeratophakia patients. METHODS: From August 1987 to January 1991, 108 consecutive patients undergoing epikeratophakia entered a prospective study aimed at evaluating both clinical results and changes in corneal physiologic parameters. After an average hospitalization of 6 days, all patients underwent complete ophthalmologic examinations at regular intervals after surgery. All postoperative complications, including the development of epithelial interface cysts, were recorded and photographed. RESULTS: Over a 3 year period, epithelial interface cysts were observed in 8 eyes, with an overall incidence of 7.4%. All cysts originated under the periphery of the epilens. In five patients, the cysts enlarged centripetally but eventually ceased to grow, causing no visual impairment. In two patients, after an initial increase in size the cysts slowly regressed and finally disappeared. In only one patient, a cyst migrated over the visual axis, thus necessitating surgical removal. The cyst did not recur during an observation time of 18 months after debridement, allowing full recovery of visual acuity. CONCLUSION: The incidence of epithelial interface cysts after epikeratophakia is relatively high. Because of their peripheral location and self-limited growth, the clinical significance of this complication is low. The possibility of spontaneous regression of the cysts supports a conservative approach, as long as the visual axis is not affected. Surgical removal is possible without compromising the epi-lens and is compatible with an excellent visual outcome. PMID- 8341507 TI - Optical zone centration in keratorefractive surgery. Entrance pupil center, visual axis, coaxially sighted corneal reflex, or geometric corneal center? AB - PURPOSE: To study the differences in optical zone marking using the geometric corneal center, entrance pupil center, visual axis, and the coaxially sighted corneal reflex as centration points. METHODS: A modified autokeratometer was used to photograph the cornea in 50 volunteers under standardized levels of illumination, with the subject fixing on the keratometer target. These photographs enabled us to mark the above-mentioned centration points and measure the direction and degree of decentration. RESULTS: From the corneal intercept of the visual axis, the entrance pupil center was found up to 0.75 mm (mean, 0.34 mm) temporally, the corneal reflex was found up to 0.62 mm (mean, 0.02 mm) nasally, and the geometric corneal center was found up to 1.06 mm (mean, 0.55 mm) temporally. CONCLUSION: The ideal physiologic centration point is the corneal intercept of the visual axis. The decentration from the visual axis was least if the coaxially sighted corneal reflex was used for centration. PMID- 8341508 TI - Acanthamoeba keratitis. The value of early diagnosis. AB - BACKGROUND: The treatment of Acanthamoeba keratitis has been increasingly successful as diagnoses are made earlier. The authors investigated features of the disease and prognosis in a consecutive series of 15 patients who were treated within 1 month of initial symptoms. METHODS: A database of patients with Acanthamoeba infection presenting between March 1984 and March 1992 was analyzed. The recognition, presenting features, culture methods, results, and treatment of the early cases were reviewed to determine the reasons for a good outcome. RESULTS: Recognition depended on perineural infiltrates (11/15), uveitis (10/15), limbitis (14/15), and infiltrated epithelium; 6 of 15 patients had epithelial defects, but only 3 of 15 had ring infiltrates or ulcers. Epithelial biopsy was culture-positive in 12 of 15 patients. Most (11/15) patients needed only two anti amebal drugs. One patient only required penetrating keratoplasty for uncontrolled disease. The final visual acuity was at least 6/12 in all patients who had been treated within 1 month of first symptoms, whereas only 17 (53%) of 32 eyes of patients who presented after 1 month achieved a visual acuity of 6/12. CONCLUSIONS: Subtle diagnostic signs, supported by comprehensive microbiologic investigation, justify the immediate instigation of specific antiamebal therapy. Treatment within 1 month of onset results in a lower morbidity and a good visual outcome. PMID- 8341509 TI - Invasive squamous cell carcinoma arising from asymptomatic choristomatous cysts of the orbit. Two cases and a review of the literature. AB - BACKGROUND: Epithelial choristomatous cysts are common orbital lesions, the most frequent of which are dermoid or epidermoid tumors. Massive enlargement or extraorbital extension of these benign lesions may occur. Malignant transformation of the epithelial lining of epidermoid cysts is rarely reported. METHODS: Two patients are presented in whom the epithelial lining of a previously asymptomatic choristomatous cyst of the orbit underwent malignant transformation to produce invasive squamous cell carcinoma. The unusual origin and clinical presentation of the lesions caused a delay in the diagnosis and therapy in both patients. Metastatic workup was negative in both patients, who underwent resection of their tumors via orbital exenteration with craniofacial resection. Reported cases of malignant transformation in analogous choristomatous cysts elsewhere in the cranium are reviewed. RESULTS: One patient is alive and well without recurrent disease 40 months postoperatively. The second patient died of a pulmonary embolus 2 months postoperatively. Autopsy showed no residual tumor. Overall, only 3 of 18 reported patients with epidermoid choristoma of the head and orbit with malignant transformation were alive when reported. CONCLUSIONS: Malignant squamous metaplasia is believed to be a rare complication of orbital dermoid or epidermoid cysts, with only two previously reported cases. However, malignant transformation is relatively frequent in analogous epidermoid cysts found elsewhere in the cranial vault, especially after incomplete excision. These reports encourage the complete removal of epithelial choristomas of the orbit. PMID- 8341510 TI - Changes in retinal nerve fiber layer thickness after reduction of intraocular pressure in chronic open-angle glaucoma. AB - PURPOSE: The authors evaluated the relative nerve fiber layer height changes in glaucomatous eyes after reduction of intraocular pressure (IOP) after trabeculectomy using image analysis techniques. METHODS: Optic disc topography and relative nerve fiber layer height of 12 eyes of 12 patients with chronic open angle glaucoma were measured using a Rodenstock optic nerve head analyzer and Caprioli's program for nerve fiber layer height determination before trabeculectomy and at 2 or more months after surgery. RESULTS: Changes in relative nerve fiber layer height after surgery, as well as those in cup volume and rim area, showed statistically significant correlation with the degree of reduction of IOP (Spearman's correlation coefficient = 0.66; P < 0.05). Changes in the mean deviation of Humphrey visual field showed a slight correlation with IOP reduction (Spearman's correlation coefficient = 0.55; P < 0.1). CONCLUSION: Nerve fiber layer height changes that may occur after trabeculectomy are pressure dependent. PMID- 8341511 TI - Can the concentration of timolol or the frequency of its administration be reduced? AB - BACKGROUND: There is evidence that the ocular hypotensive effect of topical beta blockers persists for at least 24 hours once beta-blockade has been achieved. In previous studies, the highest concentration of drug generally has been used for this purpose. METHOD: Home tonometry was performed with a self-tonometer by 14 patients to study the intraocular pressure (IOP) reduction of 0.5% timolol administered once daily in the morning or in the evening and of 0.25% timolol administered in the morning. The study was masked and included washout periods before and between the different regimens. At the end of each treatment period, the IOP was monitored five times daily for 3 days. RESULTS: No significant difference in mean reduction of IOP was found between the morning instillation of once daily 0.5% timolol compared with evening instillation of 0.5% timolol. In addition, there was no statistically significant difference in the mean IOP reduction between once daily administration of 0.25% versus 0.5% timolol. CONCLUSION: This study indicates that a lower concentration of timolol maleate used once daily may achieve maximum IOP reduction. The time of the single administration appears not to make any difference. PMID- 8341512 TI - Comparison of the anterior chamber inflammatory response to diode and argon laser trabeculoplasty using a laser flare meter. AB - BACKGROUND: Diode laser trabeculoplasty (DLT) has a similar hypotensive action to argon laser trabeculoplasty (ALT). However, anterior chamber inflammatory response and laser-induced discomfort are less pronounced with DLT. The authors compared the breakdown of the blood-aqueous barrier after DLT and ALT over the time course of 1 week and the hypotensive action over 8 weeks. METHODS: Twenty five patients with uncontrolled intraocular pressure (IOP) were randomized to either DLT or ALT. If two eyes required treatment, then the second eye would be treated with the alternative laser to the first. Flare values were measured at 1, 3, 24, 48, 72, 96, and 168 hours using a laser flare and cell meter. Intraocular pressures were measured at similar intervals and at 8 weeks. RESULTS: Of 38 eyes treated, 21 underwent ALT and 17 DLT. Both forms of treatment induced a similar hypotensive effect with a significant reduction in IOP at 8 weeks compared with initial IOP (P < 0.01) (paired Student's t test). However, there was a significantly greater disruption of the blood-aqueous barrier with ALT when compared with DLT at 1, 3, and 24 hours (P < 0.001) and at 48, 72, and 96 hours (P < 0.01) (unpaired Student's t test). By 1 week, however, there was no significant difference in flare values between the two groups. Postlaser pain occurred in seven eyes treated with ALT but in no eyes treated with DLT. In addition, peripheral anterior synechiae occurred in four eyes after ALT by 8 weeks but none occurred in the DLT group. CONCLUSION: Argon laser trabeculoplasty produces a greater disruption of the blood-aqueous barrier than DLT. This may be associated with the development of complications in the anterior segment. PMID- 8341513 TI - Late argon laser suture lysis after mitomycin C trabeculectomy. AB - BACKGROUND: Argon laser suture lysis has been effectively used in the early post operative period to enhance filtration after trabeculectomy. The most substantial reductions in intraocular pressure (IOP) occur when laser suture lysis is performed during the first 2 postoperative weeks, and virtually no effect has been reported after the fourth postoperative week. Mitomycin C, used as adjunct therapy, improves the success rate of trabeculectomy in high-risk eyes and may change the time course for effective suture lysis. METHODS: The authors used late laser suture lysis in five high-risk patients after mitomycin C trabeculectomy. The mean patient age was 66.8 +/- 15.7 years, and laser suture lysis was performed an average of 13 +/- 5.8 weeks (range, 7-21 weeks) after surgery. RESULTS: The mean IOP before suture lysis was 20.2 +/- 3.8 mmHg. The average IOP reduction immediately after suture lysis was 11.4 +/- 3.9 mmHg. The average IOP 3 to 4 months after laser suture lysis was 9.4 +/- 3.4 mmHg. CONCLUSION: The authors postulate that adjunctive mitomycin C therapy markedly delays wound healing and appears to extend the period that laser suture lysis is clinically effective. PMID- 8341514 TI - Management of functional impairment due to cataract in adults. Cataract Management Guideline Panel. PMID- 8341515 TI - The classification of flaps. AB - The history of flap surgery originated several thousands of years ago. As each era of humans learned to apply the principles of anatomy, progress was made in the coverage of difficult and complex wounds. A classification scheme is important not only to organize our thinking, but also to logically plan an operation based on reconstructive requirements. The most important factor in the safe design of flaps is a fundamental understanding of the anatomy based on the arterial supply. PMID- 8341516 TI - Soft tissue reconstruction. Coverage of hand injuries. AB - The complexity of the hand necessitates careful assessment of an injury. Wound coverage requires careful appraisal of the tissue available for coverage and consideration of its functional and cosmetic aspects. The simplest yet most appropriate flap should be chosen. Local flaps can cover many wounds. Larger wounds may require significant debridement, which should be performed early using the pseudotumor technique. Free flap coverage is then indicated and should be completed within 3 days of injury if no extenuating circumstances exist. PMID- 8341517 TI - Soft tissue reconstruction. Coverage of the elbow and forearm. AB - Soft-tissue loss around the elbow can occur from trauma, burn injury, or tumor resection. Several factors, including the patient's age, sex, occupation, and general health status before injury or an operation, should be considered before choosing the method of wound closure. The surgical procedure must be tailored to the needs of the wound and the patient. This article discusses primary wound management and closure, flap coverage, and free-tissue transfer. PMID- 8341518 TI - Soft-tissue coverage of the shoulder and brachium. AB - Injuries to the upper extremity often involve bone and soft-tissue elements, as do injuries to the lower extremity. Proper reconstruction of the soft-tissue deficits in concert with bone restoration is essential to final recovery. Better understanding of the blood supply and newer concepts of managing severely injured limbs has improved the ability to manage these challenging problems. PMID- 8341519 TI - Soft tissue reconstruction. Coverage of the chest wall and spine. AB - Advances in reconstructive surgery achieved during the past decade have considerably broadened the range of options available for coverage of the chest wall and spine. Flaps can be designed to maximize function and provide bulk, bony rigidity, sensation, or function, when needed. Local musculocutaneous and muscle flaps are preferred, but, at times, a free flap is more appropriate, either because the local tissue is inadequate or because a free flap best meets the needs of the recipient site. With current techniques, donor-site morbidity, flap survival, and, ultimately, patient outcome can be optimized to a much greater extent than in years past. PMID- 8341520 TI - Soft tissue reconstruction. Coverage of hips, pelvis, and femur. AB - This article discusses coverage of the posterior and inferior pelvis, coverage of the anterolateral pelvis and hip, and coverage of the femur. Special problems associated with these procedures are addressed also. PMID- 8341521 TI - Soft tissue reconstruction. Coverage of lower leg. Rotational flap. AB - The combined orthopedic and plastic surgical approach to the injured lower extremity has permitted successful salvage of otherwise severely injured limbs. Although numerous muscle and fascial flaps have been described for all regions of the leg between the knee and foot, specific treatment regimens have become popular based on the location of the wound. Refinements in flap surgery have permitted the approach discussed in this article to become standard in the care of patients with either chronic osteomyelitis or acutely injured limbs. This article delineates the muscle and fascial flaps that are used to reconstruct these defects. PMID- 8341523 TI - Reconstructive considerations for limb salvage surgery. AB - Tumors in the musculoskeletal system are generally treated surgically, although radiation therapy and chemotherapy have greatly improved survival statistics of patients with high-grade sarcomas of the musculoskeletal system. The mainstay in treatment of nearly every primary tumor of the musculoskeletal system is surgical resection for cure. Radiation therapy and chemotherapy continue to be important adjuvants in the overall management of musculoskeletal tumors. Functional limb salvage following radical resection is now possible in most resectable cases by placement of an alloplastic prosthesis, homograft, or autogenous bone for skeletal reconstitution, followed by well-vascularized soft-tissue coverage. PMID- 8341522 TI - Treatment of chronic osteomyelitis with muscle flaps. AB - This article discusses a study of 36 patients with chronic osteomyelitis that had local or free muscle flaps. Reconstruction of chronic osteomyelitis requires infection control and assessment of soft tissue and bone. In patients with osteomyelitis with an ununited fracture or nonunion, stabilization of the fracture is needed. PMID- 8341524 TI - Coverage strategies in total joint replacement. AB - The strategy for soft-tissue management following total joint arthroplasty begins with prevention. The medical status of the patient is optimized preoperatively. Meticulous surgical technique with liberalized indication for flap closure primarily will reduce soft-tissue failures. Early identification and aggressive team management of complications are critical to decrease long-term morbidity and to obtain a good functional result. PMID- 8341525 TI - Soft tissue reconstruction. Monitoring. AB - Despite recent advances in technology, no safe and completely reliable monitoring device is available for clinical use. As a result, direct clinical evaluation remains the mainstay of post-operative monitoring efforts. Although we have found this technique to be reliable, we tend to supplement it with Doppler ultrasonography, particularly in those patients in whom the flap remains buried beneath the skin. In patients with replants, we use pulse oximetry as an adjunct to clinical findings. This has proved to be reliable in our experience. However, should any question arise concerning altered tissue perfusion, we remain liberal in our indications for reexploration. The old adage of "better safe than sorry" certainly applies, for it is much easier to reexplore a flap than to lose a potentially salvageable reconstruction. The future remains promising for techniques such as laser Doppler study and various methods of measuring transcutaneous oxygen. However, further experimental and clinical trials are necessary to determine the efficacy of these methods. PMID- 8341526 TI - Soft-tissue reconstruction in orthopedic surgery. Secondary procedures. AB - The original consulting microsurgeon should be present to assist in the identification and protection of the vascular pedicle during secondary procedures on microvascular transplants. Flap elevation, trimming, and bone graft placement should be completed during a single tourniquet time, whenever possible. Flaps can easily be resutured on the original bed while the tourniquet is still inflated. Although proximal pedicle transection is possible, it should be avoided by careful planning, because the transplanted tissue cannot be predictably expected to survive, especially with muscle transplants. The distal muscle should be transected only in situations in which the muscle inset is extremely complex. Transection in the extramuscular portion of the main pedicle may require prompt microsurgical repair in immature muscle transplants. The safest approach is to avoid the pedicle whenever additional secondary procedures are necessary following free microvascular tissue transplantation. Placement of vascular pedicles such that the anterior crest of the tibia is avoided if the Ilizarov technique is required permit uncomplicated distraction osteosynthesis. Simultaneous Ilizarov fixation and microvascular tissue transfer are safe, practical procedures for limb salvage. Placement of the Ilizarov fixator at the time of microvascular transplantation provides stable fixation and eliminates the need for a subsequent anesthetic for fixator placement. This form of stabilization, when performed at the time of microvascular tissue transfer, allows the orthopedic surgeon direct visualization of the fracture site as the fixator is placed and eliminates the need for placement of the fixation device through the transplanted tissue. Tissue expansion or suction lipectomy are sometimes needed to optimize the clinical result. PMID- 8341527 TI - External skeletal fixation and rectus abdominis free-tissue transfer in the management of severe open fractures of the tibia. AB - The management of severe open fractures of the tibia remains one of the more challenging problems facing the orthopedic surgeon. Patients who sustain high energy injuries with loss of soft tissue in conjunction with displaced comminuted fractures face high rates of delayed union, nonunion, infection, and in some instances, amputation. This article discusses materials, methods, and surgical techniques. PMID- 8341528 TI - Vascular considerations in extremity trauma. AB - Effective diagnosis and management of associated vascular injuries is imperative to minimize morbidity after extremity trauma. An algorithm is presented for the diagnostic evaluation of patients with extremity trauma. The value of physical examination and Doppler indices in identifying occult injuries is discussed. The natural history of certain occult, nonocclusive injuries suggests that nonoperative management may be considered. The intraoperative management of major arterial and venous injuries, including current controversies, is addressed also. PMID- 8341529 TI - [Experience with the screening of pregnant women for hepatitis B virus and the vertical transmission of the virus]. AB - The authors started the checking for the hepatitis B virus in pregnant women of the town Ajka and its surroundings 10 years ago and then they extended it over the whole county. They examined 33,433 pregnant women from 1980 to 1990 and found that 0.5% of them were HBV carrier state (that is 169 persons), while in endemic territories they found a higher rate (0.74%). The existence of vertical transmission can be proved by the positive data of 120 infancy born to 72 symptomless HBV carrier mothers. The frequency of transmission is 4%. At the beginning of the check-up they gave passive then active-passive immunisation to the children born to carrier mothers. The results of immunisation were controlled by clinical and laboratory tests. They suggest that their worked-out check-up and care model--which is unique in Hungary in its kind and is also a part of the programme to prevent cancer--should be introduced all over the country. PMID- 8341530 TI - [Pulsatile gonadotropin releasing hormone treatment following previous ovarian hyperstimulation]. AB - Physiological follicular maturation was achieved by pulsatile gonadotrophin releasing hormone treatment in ovarian hyperstimulatory cases induced previously by other ovulation induction methods (clomiphene, clomiphene + hCG, clomiphene + hMG + hCG). The follicular development was detected by vaginal ultrasound examination (Hitachi-3000, 6.5 MHz) in 8 cycles treated with gonadotrophin releasing hormone. During the pulsatile gonadotrophin releasing hormone treatment ovulation was found in all cases and 2 pregnancies occurred. Ovarian hyperstimulation was not noticed. Physiological follicular maturation can be induced with the pulsatile administration of gonadotrophin releasing hormone after previous ovarian hyperstimulation because using this method the hypophyseal ovarian steroid feed back mechanism remains unchanged. PMID- 8341531 TI - [Clinical significance of incomplete right bundle branch block]. AB - In authors' opinion the majority of the physicians speak about an incomplete right bundle branch block in cases of a terminal r'wave in lead V1 of the ECG, when the QRS complex is not wider than 0.12 sec. These ECG anomalies are not properly separated in the literature, either. Authors define 4 groups whose separation is possible by the analysis of leads V1 and V2. 1. Right ventricular conduction defect--the ECG width is 0.09-0.13 sec. This picture generally signs normal or only slight higher right ventricular pressure. 2. Real incomplete right bundle branch block--the terminal vector directs forward only in this group and it causes also an r' in V2 next to the high R' in lead V1. This group can be harmless, only a conduction defect, but it can mean an advanced stadium of serious right ventricular systolic or diastolic overloading, too. 3. Right ventricular diastolic overloading--the QRS width is normal. We saw this picture in slight forms of atrial septal defect. One of our conclusions was that in case of normal V1 a haemodynamic significant ASD I or ASD II can be excluded. 4. Normal variant: normal QRS width and only a very low r' in lead V1. It was seen in young patients or in patients with flat chest. Authors remark that this pattern can possibly be seen in childhood or in case of inexact ECG (V1) registration. PMID- 8341532 TI - [Pellagra--a forgotten disease]. AB - In the civilized world the traditional causes of pellagra such as hunger, malnutrition are disappeared, but the disease has not disappeared after all. In the well developed countries the current etiologic causes are the following: alcoholism, psychiatric disorders, diseases causing cachexy, malabsorption and some drugs. In the case reported by the authors the malnutrition, accompanying the chronic alcoholism was the cause of the diarrhoea, dementia and dermatitis. The correct diagnosis was established after four years of repeated psychiatrical and medical treatment. PMID- 8341533 TI - [Janos Foldi, public health officer, polyhistor]. PMID- 8341534 TI - [Self-performed cesarean section]. PMID- 8341535 TI - [Portrait of Laszlo Nemeth in numismatic art]. PMID- 8341536 TI - [Problems of translation]. PMID- 8341537 TI - [Zitazonium therapy in breast cancer]. PMID- 8341538 TI - [In defense of the Latin language]. PMID- 8341539 TI - [Endoscopic study of the small intestine]. AB - The author summarises the possibilities of small bowel endoscopy. In case of haemorrhage of unknown origin, enteroscopy may be helpful. Sonde type fiber- or video-enteroscopes can be used. This procedure is time-consuming and needs an experienced team. In case of life-threatening bleeding intraoperative enteroscopy is recommended. "Push" enteroscopy is the best, rapid method in the diagnostics of suspected diffuse intestinal diseases or circumscript lesions of the proximal small bowel. Adult or pediatric colonoscopies or jejunoscopes are available for this investigation. Endoscopic biopsy specimens are suitable for histological examination and for enzyme assay as well. Aspiration of jejunal fluid for bacteriological culture is a way for revealing of bacterial overgrowth. The author emphasises the importance of the deep duodenoscopy made by an upper panendoscope in the diagnostics of villous atrophy. PMID- 8341541 TI - [Measurement of bone mineral content by single-photon absorptiometry in children]. AB - Bone mineral content (BMC) was measured in 64 children (33 boys [aged 4-17] and 31 girls [aged 2-12]) having no signs of metabolic bone disease, at the distal third of their radius using single photon absorptiometry (SPA), to establish normative data. Relationships were studied between the obtained bone mineral content and the age, weight, as well as height of children. The obtained BMC values were compared with that of healthy Swedish and American children. Authors suggest the routine use of SPA in home children suffering from metabolic bone diseases. PMID- 8341540 TI - [Clinical picture of slow-evolving insulin-dependent diabetes mellitus]("1 1/2")]. AB - The authors investigated the difficulties of differential diagnosis in diabetes, beginning in young age. They analysed the case records of fifteen young diabetics. The authors pointed out, that clinical diagnosis, carried out early, has utmost importance both of theoretical and practical significance, for correct classification according to the type of diabetes determines the therapy. In building the diagnosis, the clinician needs correct anamnestical, clinical data, immunogenetic markers (ICA, HLA), and the capacity of endogenous insulin secretion as well. In three patients they have observed a long period without insulin treatment that could be classified as remission phase. In eleven cases the treatment has started with oral antidiabetic drugs, one patient has got at he very beginning insulin treatment. At present, there is only one patient, still taking oral drugs. This diabetics has an ICA positivity in high titer, but he is refusing the recommended exogenous insulin treatment. In all of their cases the amount of injected daily insulin is low (0.3-0.6 IU/body weight/24 hours). Authors state by their careful analysis, that in all of their 15 diabetics there is existing a slowly developing type I IDDM, I/b, or very recently 1 1/2 diabetes form. The so called autoimmune form--described originally by Bottazzo--could have been disclosed in all of their cases. PMID- 8341542 TI - [Risk of premature rupture of the fetal membranes in cases of fetal maturity]. AB - In this study data of labour, delivery and neonatal outcome were compared in term pregnancies in 100 patients with premature rupture of the membranes (PROM) amniotomy. According to the data in cases of PROM there are more unfavourable cervix findings at the beginning of labour (54%), more pathologic cardiotocograms in the first stage (14% vs. 12%), more prolonged first stages (21.5 vs 14.5 hours) more caesarean section (9% vs 7%) and more newborns were born with a 5 minute Apgar score below 8 than in the control group. Intrauterine infection was detected in 1% of all cases. The authors conclude, that careful monitoring of the fetal state and with no signs of intrauterine infection expectant management of delivery is advisable to improve to improve perinatal mortality and morbidity. PMID- 8341543 TI - [The use of a nitinol (nickel-titanium) prosthesis in the management of malignant esophageal stenosis (preliminary report)]. AB - The authors present the case of an 81-year-old male patient with cardia adenocarcinoma. The patient underwent a surgical resection. Due to local recurrence Gianturco prosthesis implantation was performed. After 5 months of unimpeded swallowing, the patient gradually lost his ability to swallow. This was caused by tumor overgrowth. The serious condition was managed by nitinol (Ultraflex) metallic prosthesis. This reticular, compressed stent is a nickel titanium based alloy. After implantation, as a result of the body temperature it assumes its original shape. After the twofold prosthesis implantation the patient had no complaints. The authors found the case worthy of presentation because of the new method and the originality of the new design. PMID- 8341544 TI - [Zoltan Ernst, pioneer of diabetology in Hungary]. PMID- 8341545 TI - [Remembering Lajos Makara]. PMID- 8341546 TI - [Management of foreign bodies in the esophagus]. PMID- 8341547 TI - [Rights of the patient]. PMID- 8341548 TI - [HIV-1 infection in cell culture]. PMID- 8341549 TI - [Current data on the pathogenesis of neurodegenerative diseases and some muscular disorders: therapeutic prospectives]. AB - Recent findings suggest that damaged mitochondrial DNA (mtDNA) may play a role in the development of Leber's hereditary optic neuropathy, Huntington's, Parkinson's and Alzheimer's disorders, as well as in that of encephalomyopathies. The mtDNA consist of 16,569 base pair and encodes 13 polypeptides, 2 ribosomal RNAs and 22 transfer RNAs. It is much more injurable than the nuclear DNA (nDNA) and since mtDNA participates in the synthesis of respiratory chain enzymes, therefore, its damage may result in neuronal cell death. The present paper summarizes these novel mechanisms and potential therapeutic strategies with regard to neurological disorders. PMID- 8341550 TI - [The role of two-dimensional echocardiography in the detection of pacemaker induced endocarditis]. AB - The authors analysed the data of eight patients who had to undergo open heart surgery because of pacemaker endocarditis in the last four years. Repeated surgical interventions on the pacemaker system was the most predisposing factor. The most common causative organisms were Staphylococcus aureus and Staphylococcus epidermidis. Two-dimensional echocardiography (2DE) had a decision making role in the diagnosis beside the clinical picture and blood culture. CONCLUSIONS: 1. Each pacemaker patient with fever must be considered to have a pacemaker endocarditis; 2. All these patients must be examined by two-dimensional echocardiography. PMID- 8341551 TI - [Economic glossary: pitfalls of interpretation]. AB - Sharp discrepancy exists between the concepts declared and the measures introduced with urgency by the government and the real praxis of the health-care institutions, which are delivered to and suffer from the heaviest financial economical restrictions. The situation may partly be attributed to the missing system-specific interpretation of some leading categories. Attempts were made to point at some harmful consequences of this failure and to reinterpret basic categories, so as to contribute to a better agreement of the participants in favour of our patients' welfare. PMID- 8341552 TI - [Congenital absence of the left pericardium. Case report and review of the literature]. AB - Congenital absence of the pericardium, whether partial or total, is a rare abnormality. If suspicion of such a malformation arises it should be classified because of possible herniation of the atrium or ventricle. The authors report the case of an asymptomatic young male patient in whom the diagnosis was suggested radiographically, electrocardiographically (total electrical alternans has been noticed) and confirmed by cross-sectional echocardiography, computed tomography and magnetic resonance imaging. Only in exceptional cases should it be necessary to perform an exploratory thoracotomy. In patients with complete pericardial defects no specific therapy is indicated, however, in patients with partial defects surgical treatment is indicated. Congenital pericardial defects are not completely benign, as has been suggested before. PMID- 8341553 TI - [Gyula Varannai, M.D. (1905-1993)]. PMID- 8341554 TI - [Pentoxyphylline and lymphocyte migration]. PMID- 8341555 TI - [Fresh osteochondral transplants in the treatment of advanced giant cell tumors]. AB - Eighteen patients with advanced giant cell tumors were treated with complete tumor resection and reconstruction using fresh osteochondral allografts. All patients had one or more of the following indications for tumor resection (as opposed to curettage): tumor recurrence, pathological fracture, or destruction of the subchondral bone plate. At the 4- to 16-year follow-up (mean 9 years), two grafts were revised to a second fresh graft because of fracture, one graft was converted to an allograft implant composite and two joints were fused because of infection. The functional results were assessed in 14 patients: 9 were good or excellent, 4 fair and 1 poor. We conclude that the fresh osteochondral allograft is a viable treatment alternative to prosthetic replacement in advanced benign, aggressive bone tumors. PMID- 8341556 TI - [Rotation grafts]. AB - Nowadays rotationplasty is well established as an acceptable procedure for limb salvage in patients who have a malignant tumor in the femur or tibia. The main indication is that it is the alternative to amputation. Rotationplasty should be used in very young children because of the growth-dependent complications that can be expected after tumor resection. The different types of rotationplasty, the operative technique, prosthetic care, and the results of 104 patients are shown. PMID- 8341557 TI - [Tumor endoprosthesis in malignant bone tumors]. AB - In the Department of Orthopedics at the University of Vienna, tumor endoprostheses have been implanted after resections of tumors of the upper extremities since 1974 and of the knee joint since 1976. For replacement of the humerus after tumor resection, a system of modular tumor endoprostheses was developed very early. Initially, it was ceramic and later on made of titanium alloys, which were also implanted in combination with custom-made prostheses with cementless stem-plate fixation in 57 patients until February 1990. In 43 of these patients (75.4%) adequate resection (2 radical and 41 wide) had been performed. Of 49 patients with a follow-up period of at least 24 months, 36 patients had a mean disease-free survival time of 106.1 months. Between 1976 and 1981, 16 custom made endoprostheses were used after tumor resection of the knee joint. Since 1982 we have used a modular system of tumor endoprostheses suitable for replacement of the proximal and distal femur, proximal tibia, total femur and total knee joint. Of 75 patients who had been operated on up to February 1990, 67 patients (89.3%) had undergone adequate resection (2 radical and 65 wide). Out of 32 of these patients, 24 (75%) exhibited a disease-free survival time of at least 24 months (mean 48.2 months). Out of 213 patients with resection/reconstruction (160 endoprostheses), 77.8% had a survival time of at least 24 months, a results which is considerably better than in 146 patients with amputation in which case the respective value was 69.4%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341558 TI - [Partial endoprosthetic reconstruction of the pelvis in malignant tumors]. AB - Twenty-five patients underwent an internal hemipelvectomy with endoprosthetic reconstruction of the pelvis for primary bone tumor (n = 17) or bone metastasis in the pelvis (n = 8). According to the Enneking tumor classification system, there were 9 stage II B tumors and 16 stage III. Conventional metal or polyacetal prostheses were used in 5 cases, and in 20 anatomically adaptable modular prostheses with intramedullary anchorage were implanted. In the last 11 cases a 3D CT-controlled manufactured model of the pelvis was used. The functional results according to Enneking were good in 5 cases, fair in 11, and poor in 7. The last endoprosthetic system showed better results, because it is easier to implant and the possibility failure is reduced. The learning curve of the surgeon is important, too. PMID- 8341559 TI - [Resection of pelvic sarcomas. Reconstruction techniques without use of endoprostheses]. AB - Advances in preoperative imaging techniques and surgical expertise now permit limb sparing resections of pelvic sarcomas to be performed in appropriate patients with an acceptable risk of local recurrence. Reconstruction of the skeletal defect remains, however, problematic. Many techniques have been employed, all with advantages and disadvantages. Arthrodesis for the unstable pelvis has been our preferred reconstructive procedure. When successful, we find this a durable and pain-free reconstruction for the young, active patient. PMID- 8341561 TI - [Resection arthrodesis of the proximal ankle joint in Ewing's sarcoma. Maintenance of leg length using distraction osteogenesis]. AB - The technique of segmental transport of the tibia according to Ilzarov is a well known procedure in pediatric orthopedics, but in the treatment of bone tumors it has not yet been established. The method is also applicable for filling a large gap after tumor resection in the distal tibia. A case history is presented in which Ewing's sarcoma localized in the distal tibia was removed surgically after multiagent chemotherapy. The ankle joint was successfully fused after bone transport of the tibia 5 cm distal to the talus. PMID- 8341560 TI - [Intraoperative radiotherapy in malignant bone tumors]. AB - When a bone tumor is confirmed to be malignant by biopsy and has not expanded into the soft tissue, intraoperative radiation therapy (IORT) is indicated for most parts of the four extremities. The irradiation area is exposed through an extensive skin incision, and the soft tissues are opened and retracted away from the irradiation area, leaving a layer of normal tissue directly covering the tumor. The irradiation is performed with 12-26 MeV electron beams from a betatron at a dose of 50-100 Gy, depending on the radiosensitivity of each tumor. The multifocal bilateral irradiation method is the best for minimizing complications of the soft tissues. Since 1978, we have performed IORT in combination with chemotherapy in 41 cases of malignant bone tumors and experienced only five cases of tumor recurrence one in the irradiated area and four in the non-irradiated area. Joint function in the irradiated limb was excellent. However, due to the high incidence of pathological fracture after IORT in osteolytic tumors, the limb eventually had to be replaced by a prosthesis. After 1984 when cisplatinum was introduced to our chemotherapy protocol, the cumulative 5 year survival rate increased to 81%, with the irradiated lesion preserved in situ in osteoblastic tumors and replaced with a prosthesis in osteolytic tumors. PMID- 8341562 TI - [Tumor resection and reconstructive intervention in spinal tumors]. AB - Modern techniques of resection and reconstructive surgery in patients with primary and metastatic spine tumors are presented. These techniques are delineated along an algorithm that allows us to develop an adequate oncological protocol, find a rational approach for preoperative embolization and for tumor resection and choose the proper materials and implants for bridging bone defects. The aim is to achieve short-term and long-term stability, respectively. These principles are illustrated by different examples and our own results in spinal metastasis surgery. PMID- 8341563 TI - Should intravenous therapy teams be responsible for peripheral venous access? PMID- 8341564 TI - Long-term care a priority issue for patients with cancer. PMID- 8341565 TI - The evolution of otosclerosis surgery. AB - This article reviews the development of surgical methods over the centuries to improve hearing loss due to otosclerosis. Pioneers in the development of surgical techniques for otosclerosis discussed in this article include Holmgren, Lempert, Rosen, and Shea. Also discussed are the personal experiences of the author, witness to many of this century's technologic developments and founder of the House Ear Institute in Los Angeles, California. PMID- 8341566 TI - Histopathology of otosclerosis. AB - This histopathologic review illustrates that otosclerosis is a very pleomorphic bone dyscrasia. It may fix the stapes by a tiny bridge of abnormal bone or may totally obliterate it. It may spread to the cochlea to produce either a sensorineural loss of varying degree or deafness. Lesions may be sclerotic, spongiotic, or fibrous but usually comprise all these histologic types. This diversity of size and anatomic distribution coincides with the variable types of hearing loss, from a mild conductive deficit to a total loss. In spite of more than a century of investigation of otosclerosis, an etiologic agent other than heredity has not been established. PMID- 8341567 TI - Physical examination and clinical evaluation of the patient with otosclerosis. AB - A detailed history, otoscopic examination, and testing with tuning forks are essential to the diagnosis of otosclerosis. These steps, including a differential diagnosis to rule out those middle ear conditions that can masquerade as otosclerosis, can help the examining physician make the presumptive diagnosis of otosclerosis. PMID- 8341568 TI - Imaging of otosclerosis. AB - Imaging studies play an important role in the diagnosis of otosclerosis and in the clinical management of this disease. CT scanning at present is the tool of choice for the assessment of the labyrinthine windows and cochlear capsules. MR imaging thus far has had limited applications in the examination of the cochlear capsules but has been more useful in the assessment of the cochlear lumen prior to cochlear implant in patients with profound bilateral hearing loss. PMID- 8341569 TI - Audiologic characteristics of the patient with otosclerosis. AB - The audiologic manifestations of otosclerosis are as distinctive as they are varied. When pure stapedial otosclerosis is present, the most prominent audiologic signs are elicited in response to the use of low-frequency stimuli, reflecting the effect that increased stiffness has on the transfer function of the middle ear. Characteristic abnormalities appear on tympanometry, acoustic reflexes, and the pure-tone audiogram. When the disease process extends into the cochlea, a sensorineural hearing loss develops, which may be accompanied by vestibular symptoms and/or tinnitus. Complete audiologic evaluation may prove to be uniquely helpful both in establishing a diagnosis by recognizing the characteristic patterns of stapes fixation and in planning for the surgical, medical, or hearing aid management of the patient with otosclerosis. PMID- 8341570 TI - Stapedectomy technique. AB - This article reviews the evolution of the author's stapedectomy technique from total footplate removal with single loop wire prosthesis and Gelfoam seal to small fenestra stapedectomy with platinum ribbon piston prosthesis and blood seal. The author concludes that the microdrill is effective, safe, and cost effective for performing this procedure. Since using this technique, the author has had no cases of sensorineural hearing loss and few complaints of dizziness or vertigo. PMID- 8341571 TI - Surgical treatment of stapes fixation by fiberoptic argon laser stapedotomy with reconstruction of the annular ligament. AB - The goal of surgical treatment of stapes fixation is to restore the impedance transfer of the ossicular chain and the acoustic impedance of the annular ligament of the stapes footplate to achieve normal physiologic vibration of the inner ear fluids. Advances in instrumentation, particularly the introduction of fiberoptic laser handpieces and microdrills, have enabled surgeons to approach this goal in a more precise and delicate fashion. In this article, the authors review their surgical techniques, the biophysics involved, the physics of fiberoptic handpieces for the delivery of argon laser energy, and their results. PMID- 8341572 TI - Carbon dioxide lasers for otosclerosis. AB - Over the past eight years, the senior author (SGL) has sought the ideal microsurgical laser for otosclerosis surgery. This quest required learning the principles of laser physics and of the interactions of light with matter. Rather simple thermocouple experiments were performed in the laboratories of the Midwest Ear Foundation (MEF) to confirm some of what was predicted from these principles. More sophisticated transmission spectroscopy experiments were performed at the Massachusetts Institute of Technology (MIT) to evaluate which electromagnetic wavelengths are best absorbed by collagen and bone. MIT's spectroscopy studies paralleled MEF's thermocouple data. CO2 laser energy (10.6 microns) is nearly completely absorbed by collagen and bone, whereas visible argon and KTP laser energy (0.5 micron) is poorly absorbed. Despite the better optical precision of visible lasers, the author chose the CO2 laser for stapedectomy revision and stapedotomy, because long infrared electromagnetic energy has vastly superior tissue absorption characteristics for these procedures. With the development of I. L. Med's Unilase, the otologic surgeon now has a CO2 laser with optical precision and convenience approaching that of visible lasers. Clinical studies of 102 consecutive CO2 laser stapedectomy revisions show that in 92% of patients, hearing was significantly improved with the new CO2 laser revision techniques. Nearly half of these patients had undergone one or more previous, unsuccessful, nonlaser revisions. For primary otosclerosis, CO2 laser stapedotomy has simplified a technically difficult operation while significantly reducing mechanical trauma to the inner ear. Most gratifying to the senior author is that after approximately 450 consecutive CO2 laser operations for otosclerosis, no patient has experienced significant postoperative sensorineural hearing loss (greater than 15 dB; mean 500, 1000, 2000, 3000 Hz). This fact alone has justified our theoretical and laboratory efforts to find the safest laser for otosclerosis surgery. PMID- 8341573 TI - Evolution of techniques of stapedectomy from the total stapedectomy to the small fenestra stapedectomy. AB - No consensus exists among surgeons about how much of the footplate to remove in stapes surgery. By comparing ideal cases with identical surgical techniques, it may be possible to select an optimal amount of the stapes footplate to remove. This article details the evolution of techniques of stapedectomy from the total stapedectomy to the small fenestra stapedectomy. PMID- 8341574 TI - Stapedectomy. Causes of failure and revision surgery in otosclerosis. AB - The greatest chance of success in stapedectomy is at the time of the initial procedure. Complications are compounded and successes markedly decreased when revision surgery is attempted. The most common pitfalls encountered in stapedectomy are reviewed in this article. Principles of surgery that have minimized complications and decreased the need for revision procedures in the authors' practices are outlined. Guidelines helpful when considering revision surgery also are presented and specific indications are addressed. PMID- 8341575 TI - Complications in stapes surgery. Options for prevention and management. AB - Although successful stapedectomy is very gratifying for both the patient and surgeon, complications can arise, often with disastrous results. Certain clues may alert the surgeon to risk prevention or possible complications, allowing early definitive management. This assumes critical importance today as fewer younger surgeons acquire extensive experience in stapedectomy. A thorough knowledge of possible problems and their management is mandatory for the otologist who undertakes this most challenging of operations. PMID- 8341576 TI - Hearing aids and otosclerosis. AB - The purpose of this article on the use of hearing aids in patients with otosclerosis is to emphasize that all otosclerosis patients cannot be assumed to be good users of hearing aid amplification. Patients with losses of 60 dB or less and with purely conductive lesions may be able to use aids well. Individuals with mixed-type impairments due to otosclerosis may have significant problems utilizing amplification. These cases demonstrate the use of hearing aid amplification in patients with mixed-type hearing impairment due to otosclerosis. This is a very different group of patients from the group with a pure conductive lesion, in which there is little problem in fitting a hearing aid, provided that the instrument has sufficient power and gain to override the loss. A special subgroup of patients who have far-advanced otosclerosis and have successful stapes surgery to correct the conductive component of their hearing loss present a unique problem. They may initially suffer from severe recruitment requiring patience, special training and compression-type hearing aids. PMID- 8341577 TI - Early identification of hearing impairment in infants and young children. Summary of the NIH Consensus. PMID- 8341578 TI - Empowering women for the future. PMID- 8341579 TI - Heterogeneity in patterns of malarial oocyst infections in the mosquito vector. AB - Oocyst prevalence and intensity have been recorded in 349 laboratory infections of Anopheles stephensi with Plasmodium berghei. Intensity and prevalence of infection are shown to be predictably related. The structure and heterogeneity in the infections has been analysed with the objective of describing the biological mechanisms by which the observed negative binomial oocyst distributions are generated. The analysis has revealed that the most likely processes lie within the population dynamic events of malaria within the mosquito, namely gametogenesis, fertilization and mortality. The distribution is similar in all Plasmodium-mosquito combinations examined so far, whether they are of laboratory (P. gallinaceum in Aedes aegypti) or field (P. vivax in An. albimanus and P. falciparum in An. gambiae s.l. and An. funestus) origin. Further we conclude that there is competition between parasites in the vector. Oocyst frequency distribution analysis shows that under natural conditions of transmission intensity, and even under the best laboratory conditions, significant numbers (> 10%) of fully susceptible mosquitoes will not be infected under conditions where the mean infection is as high as 250 oocysts. Failure to infect is not therefore an absolute indicator of refractoriness. In assessing transmission data it is shown that sample sizes should not be less than 50, and ideally 100 mosquitoes, if reliable data are to be obtained. In field it is suggested that difficulties in determining the low natural intensity of oocyst infections indicate that prevalence estimates are a useful and accessible parameter to measure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341580 TI - Immunogenicity of a hybrid Plasmodium falciparum malaria antigen. AB - A recombinant baculovirus-expressed hybrid protein containing epitopes for the C terminal fragment of the Plasmodium falciparum precursor to the major merozoite surface antigens (PMMSA) and the tetrapeptide repeats of the circumsporozoite protein (CSP) was assessed for its immunogenicity. Murine MHC-II restriction of the antibody response to the CSP repeats was not overcome by the PMMSA component, the response to which showed no restriction. In an adjuvant trial the highest antibody titres in rabbits to both components of the hybrid were obtained using Freund's adjuvant. Lack of a boosting antibody response to the CSP repeats appeared to be linked to the conformation of the PMMSA component. Formulation of the hybrid protein into Iscoms gave antibody titres of only short duration to both components. PMID- 8341581 TI - Immunization of pigs against infection with Schistosoma japonicum using ultraviolet-attenuated cercariae. AB - Since pigs are important in the zoonotic transmission of schistosomiasis japonica in China, a veterinary vaccine might contribute to the control of the disease in humans. Pigs were immunized with three doses each of 10,000 cercariae of Schistosoma japonicum attenuated with ultraviolet light (400 microWatt.min/cm2). The experiment was performed with portable irradiation equipment in a rural area of the Hubei Province (P.R. China). A challenge infection of 1,000 untreated cercariae was given 2.5 or 6 months after the last immunization, and age-matched naive pigs were challenged as a control. Immunized pigs developed about 90% resistance against the challenge. The liver egg load of these animals was reduced by over 90%. Less than 0.01% of the immunizing cercariae developed to adult parasites and the vaccination had no apparent adverse influence on the pigs' health. PMID- 8341583 TI - Voltage-gated currents in muscle cells of Schistosoma mansoni. AB - Three morphologically distinct types of muscle fibres isolated from the platyhelminth Schistosoma mansoni have been studied with whole cell current- and voltage-clamp techniques. Fibres showed a marked time-dependent decrease in membrane resistance in response to depolarizing current injections. Voltage-clamp experiments revealed the presence of two distinct voltage-gated outward currents. The most prominent current is a slowly activating, slowly and incompletely inactivating potassium current similar to delayed rectifier currents which have been described in a variety of cell types from a variety of organisms. Also present is a faster activating, quickly and completely inactivating potassium current that shares functional characteristics with 'A'-currents. All three of the cell types studied possess a delayed rectifier current, but only two of the three types have 'A'-currents. Though depolarization with high K+ leads to contraction of the dispersed fibres, no voltage-gated inward currents could be detected by whole cell voltage-clamp under any of our conditions. PMID- 8341582 TI - Mechanisms involved in the loss of antibody-mediated adherence of macrophages to lung-stage schistosomula of Schistosoma mansoni in vitro. AB - Sera from rabbits vaccinated with irradiated cercariae mediated cell (P388D1 or mouse peritoneal macrophage) adherence to lung-stage schistosomula (LS) but such antibody-mediated cell adherence was short-lived in contrast to cell adherence to mechanically transformed schistosomula (MS). Thus LS lost 50% of their adherent cells within 3-6 h in culture and up to 90% by 24 h, whereas adherence to MS was undiminished during this time. Rapid loss of adherent cells was unique to schistosomula that had developed to the lung stage because schistosomula recovered from the skin up to 3 days post-infection did not exhibit the rapid cell loss shown by 3-day LS. To determine whether cell loss was caused by loss of surface antigenicity during culture LS were cultured on their own for up to 24 h and at various intervals samples of schistosomula were tested for antigenicity by addition of immune serum and cells. Levels of adherence to both MS and LS were maintained throughout the incubation period. When antibody-opsonized schistosomula were washed and indicator cells added at progressive intervals, persistence of adherence was again demonstrated, showing that antibody binding to LS had not promoted surface antigen loss or degradation of bound antibody. It was then shown, by adding fresh macrophages to cultures up to 24 h old that LS which had lost their adherent cells nevertheless retained bound antibody, and comparison of adherence of 'used' and 'fresh' cells to MS and LS showed that the cytoadherence properties of macrophages were not significantly reduced during their culture with LS from which cells had been lost.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341584 TI - Epidemiology of trypanosome infections of the tsetse fly Glossina pallidipes in the Zambezi Valley. AB - The epidemiology of trypanosome infections of Glossina pallidipes was studied at a riverine site in the Zambezi Valley, Zimbabwe for a period of 13 months. Over 9000 flies were captured using a single trap. These flies were dissected, screened for trypanosome infection, sexed, and aged using both wing fray and (for females) ovarian category indices. Midgut infections were identified to species using recently developed DNA probes. The overall prevalence of mature infections was 5.5%, comprising 3.1% Trypanosoma vivax-type and 2.4% T. congolense-type (which included very low prevalences of T. brucei, T. simiae and another Nannomonas species). The prevalence of infection increased with age. For T. vivax type infections in flies aged by ovarian category this relationship could be described by a simple 'catalytic' model assuming a constant per capita rate of infection. For T. congolense-type infections this model tended to over-estimate prevalence in older age classes, implying that the rate of infection decreases with age, and/or that infected flies have higher mortality rates, and/or that a significant fraction of the population is resistant to infection. Prevalences of infection also varied between months. This variation was more marked for T. vivax type infections and was negatively correlated with both temperature and rainfall. The shape of the age-prevalence relationship, however, did not vary significantly between months. These observations are not fully explained by variation in the age-structure of the tsetse population and are consistent with temporal variation in the rate of infection (rather than in the trypanosome developmental period or in effects of infection on fly mortality). Possible causes of this variation are discussed. PMID- 8341585 TI - Characterization of the cysteine proteinases of the common liver fluke Fasciola hepatica using novel, active-site directed affinity labels. AB - The excreted/secreted proteinases of adult and juvenile Fasciola hepatica maintained in vitro were found to hydrolyse the fluorogenic substrates Cbz-Phe Arg- and Cbz-Arg-Arg-NHMec. This activity was demonstrated to have a classical cysteine proteinase inhibitor profile, with turn-over of both substrates being blocked by pre-incubation with E64 and peptidyl diazomethanes. The Cbz-Arg-Arg NHMec hydrolysing activity of the mature fluke exhibited an alkaline stability not characteristic of its mammalian lysosomal counterparts. Further, the biotinylated affinity reagents biotin-Phe-Ala-CHN2 and biotin-Phe-Cys(SBzyl)-CHN2 were used to label and characterize these cysteine proteinases in terms of apparent molecular weight and subsite specificity. Adult fluke media were found to contain four species of molecular weights 66, 58, 50 and 25-26 kDa; juvenile media contained three species of molecular weights 66, 54 and 25-26 kDa. The major 25-26 kDa cysteine proteinase common to both stages was shown to have a subsite specificity similar to that of mammalian cathepsin B. PMID- 8341586 TI - Establishment, survival, site selection and development of Leptorhynchoides thecatus in largemouth bass, Micropterus salmoides. AB - Establishment, survival and distribution of Leptorhynchoides thecatus (Acanthocephala) were investigated in largemouth bass, Micropterus salmoides, fed 10, 25, or 40 cystacanths and examined at 1, 3 or 5 weeks post-infection. Worms established widely in the alimentary tracts of bass but by 5 weeks post-infection had localized in the pyloric caeca and intercaecal region. Other individuals moved to parenteral sites where they remained immature, though viable. In the 10- and 25-level exposures, establishment and survivorship in the alimentary tract were roughly proportional to the dose of cystacanths. After 1 week post-infection in the 40-level exposure class, numbers of worms in the alimentary tract decreased significantly and parenteral occurrence increased significantly. Total survival of L. thecatus appeared to be density-independent. Maturation of worms was retarded temporarily as intensity of infection increased, but by 5 weeks post infection worms from all doses were at roughly the same stage of development within sex. The caeca and intercaecal area apparently did not differ in their suitability for maturation. PMID- 8341587 TI - The potential of vervet monkeys (Cercopithecus aethiops) and baboons (Papio anubis) as models for the study of the immunology of Echinococcus granulosus infections. AB - Nine vervet monkeys and nine baboons were infected with eggs of Echinococcus granulosus per os. Six of the vervets and one of the baboons possessed hydatid cysts at autopsy, 15-28 months post-infection. The sequential IgG response to hydatid fluid and protoscolex antigens showed considerable inter-animal variation. Infected vervets and baboons became seropositive after an average of 8 months post-infection. Considerable fluctuation in the IgG response was observed, particularly to the hydatid fluid antigen which, in humans, may contribute to the existence of a significant proportion of seronegative individuals. Vervets, in particular, may be useful to study immunological events associated with exposure, development and resolution of hydatid disease in outbred human populations. PMID- 8341588 TI - Spatio-temporal structure of the communities of helminths in the digestive tract of Sciaena umbra L. 1758 (Teleostei). AB - The helminth community in the digestive tract of the sedentary predatory fish, Sciaena umbra, near the Scandola Nature Reserve, Corsica, consists of 5 species of digeneans. Anoiktostoma coronatum (in the rectum) and Metadena pauli (in the intestine) were found in almost all the fish, and in high numbers; they are considered core species. Distomum aloysiae, Pleorchis polyorchis (both in the intestine), and Stephanostomum bicoronatum (in the rectum) were relatively uncommon, usually found in small numbers, and are considered satellite species. The two core species were very abundant in June, when the size of their populations was strongly correlated with the size of the host fish. At this time, M. pauli was found mainly in the duodenum, but in high populations was spread throughout the intestine (s. strict.). Both species were much less abundant in October, their populations were less dependent on host size, and M. pauli was more limited to the anterior intestine. Pleorchis polyorchis and Distomum aloysiae were more frequent in October, were found predominantly in fish with few M. pauli, and were found posterior to M. pauli, suggesting some interactions between these species. Stephanostomum bicoronatum showed no seasonal patterns, and no apparent interactions with A. coronatum. PMID- 8341589 TI - Detection of density-dependent growth and fecundity of helminths in natural infections. AB - Density-dependent constraints on parasite growth, survival or reproduction are thought to be important in preventing the unchecked increase in parasite numbers within individual hosts or host populations. While it is important to know where, and with what severity, density dependence is acting within the parasite life cycle, interpretation of data from natural infections is difficult. In this paper, we present a Monte Carlo simulation technique for examining such data for evidence of density dependence. We also describe how this technique may be used to distinguish among mechanisms hypothesized to generate density-dependent phenomena. PMID- 8341590 TI - Activation of the cryptic DNA binding function of mutant forms of p53. AB - Wild type p53 assembles into a latent multiprotein complex which can be activated for sequence-specific DNA binding in vitro by proteins targeting the carboxy terminal domain. Using an optimized system coupling the post-translational modification of wild type p53 to activation of sequence specific DNA binding, we examined the affects of common mutations on the cryptic DNA binding function of p53. Two mutant forms of p53 were shown to be efficiently converted from the latent state by PAb421 and DnaK, but were defective in activation by casein kinase II, indicating that mutant p53 may not be receptive to allosteric regulation by casein kinase II phosphorylation. A reactive sulfhydryl group is absolutely required for DNA binding by wild type and mutant forms of p53 once converted to the activated state. Together, these data show that some mutant forms of p53 harbour the wild-type machinery required to engage in sequence specific DNA binding and define a signalling pathway whose inactivation may directly result in a loss of p53 function. PMID- 8341591 TI - A novel Brn3-like POU transcription factor expressed in subsets of rat sensory and spinal cord neurons. AB - Brn3a and Brn3b are mammalian members of the POU class of transcription factors. They are closely related to each other and to Unc86, which determines the normal development of certain cells, including mechanoreceptive sensory neurons in Caenorhabditis elegans. We screened a rat dorsal root ganglion (DRG) cDNA library at moderate stringency with a Brn3a POU-domain probe and identified a novel transcript encoding a POU protein that we have named Brn3c. Brn3c closely resembles Brn3a and Brn3b in its POU-domain and thus helps define a family of Unc86-related mammalian POU factors. Both Brn3a and Brn3c are expressed only in the central and peripheral nervous systems. In the neonatal rat, northern blots revealed a 3.6 kb Brn3a transcript in DRG, spinal cord and hindbrain, and a 2.6 kb Brn3c transcript in DRG and spinal cord. In situ hybridization showed that most DRG neurons express Brn3a whereas only a small subset of neurons expresses Brn3c. In the spinal cord, Brn3a is expressed by many dorsal horn neurons. In contrast, Brn3c is expressed by a very small number of cells in laminae 4/5 of the dorsal horn. These data suggest that Brn3-related POU factors may be involved in the development or function of particular subclasses of sensory and spinal cord neurons. PMID- 8341592 TI - The role of the preserved sequences of Dam methylase. AB - We have undertaken a site directed mutational analysis of two of the preserved regions in the amino acid sequence of Dam methylase in order to characterize their role. Mutations in region IV (sequence DPPY) abolish catalytic activity and greatly affect AdoMet crosslinking. Mutants in region III display a lowered specific activity with an unchanged AdoMet crosslinking capacity. We have also made a series of deletions both at the N and C terminal parts of the protein, which have been found to provide inactive enzyme. We discuss the significance of these results for the understanding of the functional properties of the enzyme. PMID- 8341593 TI - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a powerful tool for the mass and sequence analysis of natural and modified oligonucleotides. AB - We report the analysis and characterization of natural and modified oligonucleotides by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The present technology was highly improved for this class of compounds by using a new matrix, 2,4,6-trihydroxy acetophenone, together with di- and triammonium salts of organic or inorganic acids to suppress peak broadening due to multiple ion adducts. This methodology can be used in combination with time dependent degradation of oligonucleotides by exonucleases as powerful tool to determine sequence compositions. PMID- 8341594 TI - Antipairing and strand transferase activities of E. coli helicase II (UvrD). AB - The product of the uvrD gene of Escherichia coli, UvrD (helicase II), is known to be involved in methyl-directed mismatch repair, transposon excision and uvrABC excision repair. In conjugational crosses, various uvrD mutants have been reported to result in higher, lower or unaffected recombination frequencies. In an attempt to clarify the role of UvrD in recombination, we have studied in vitro its effects on two key reactions driven by RecA, homologous pairing and strand exchange. We show here that UvrD efficiently prevents or reverses RecA-mediated homologous pairing. Unexpectedly, we also found that it can stimulate RecA-driven branch migration and even catalyze strand exchange in the absence of RecA. A possible in vivo role for these antagonistic activities is discussed. PMID- 8341595 TI - A protein containing conserved RNA-recognition motifs is associated with ribosomal subunits in Saccharomyces cerevisiae. AB - Using PCR cloning techniques, we have isolated a Saccharomyces cerevisiae gene encoding a protein that contains two highly conserved RNA-recognition motifs. This gene, designated RNP1, encodes an acidic protein that is similar in sequence to a variety of previously isolated RNA binding proteins, including nucleolin, poly (A) binding protein, and small nuclear ribonucleoproteins. The RNP1 gene maps to the left arm of chromosome XIV centromere distal to SUF10. Haploid yeast containing a null allele of RNP1 are viable, indicating that RNP1 is dispensible for mitotic growth. However genomic Southern blot analysis indicated that several other loci in the S. cerevisiae genome appear to contain sequences similar to those in the RNP1 gene. The majority of the Rnp1 protein is cytoplasmic. Extra copies of RNP1 cause a decrease in levels of 80S monoribosomes. A fraction of Rnp1 protein cosediments on sucrose gradients with 40S and 60S ribosomal subunits and 80S monosomes, but not with polyribosomes. PMID- 8341596 TI - Interlocked circle formation by group I introns: structural requirements and mechanism. AB - Precursor RNA transcribed from the yeast mitochondrial gene coding for the large ribosomal RNA contains a group I intron that can excise itself in vitro. Apart from group I specific sequence elements the intron also contains a gene encoding a DNA endonuclease involved in intron dispersal. A precursor RNA derivative from which this gene has been removed self-splices efficiently, but due to activation of cryptic opening sites located in the 5' exon, the 3' part of this exon is sometimes co-excised with the intron. Upon further reaction, this enlarged intron molecules give rise to interlocked circles, comprising small circles derived from 5' exon parts and large circles of the intron. Sequence comparison between cryptic opening sites and authentic splice sites reveals in most cases homology with the 3' exon part that is capable of interacting with the Internal Guide Sequence. The role of the IGS was further substantiated by replacing the cryptic opening sites with well defined sequences of authentic splice sites: one corresponding to the 3' splice site and its mutant derivatives, the other to a fragment containing the natural 5'-3' exon junction. Precursor RNAs derived from these constructs give rise to interlocked circles, and mutation studies confirm that the 3' exon nucleotides flanking a 3' splice site are essential for their formation. The results underline the crucial role of the IGS in interlocked circle formation which behaves similarly as in the normal self-splicing reactions. It has been proposed that the two short helices formed by basepairing of the IGS with the 5' and 3' exon can co-axially stack on top of each other forming a quasi continuous RNA double helix or pseudoknot. We present a model explaining how transesterification reactions of a mutant precursor RNA in such a pseudoknot can lead to interlocked circles. The experiments support the notion that a similar structure is also operative in splicing of wild type precursor RNA. PMID- 8341598 TI - Synthesis of (3'-5'),(2'-5')-linked di- and tri-adenylyl methylphosphonate analogs. AB - Stereoselectivity was found during the coupling reaction, to form 2',5'- and 3',5'-linked di- and triadenylyl methylphosphonate. The configuration of phosphorus was determined by 1HNMR NOE. PMID- 8341597 TI - Determination of DNA replication kinetics in synchronized human cells using a PCR based assay. AB - Studies on the temporal order of DNA replication are difficult due to the lack of sensitivity of methods available for replication kinetic analysis. To overcome problems associated with the current techniques, we propose a PCR-based assay to determine the replication time of any single-copy DNA sequence in complex genomes. Human cells labeled with 5-bromodeoxyuridine (BrdU) were flow sorted, according to their DNA content, at different times after synchronous release from the G1/S phase boundary. The selective removal of newly-replicated BrdU substituted DNA was achieved by UV light irradiation followed by S1 nuclease treatment. The timing of replication of selected DNA sequences (housekeeping, tissue-specific, and non-coding loci) was determined by polymerase chain reaction (PCR) amplification using appropriate primers. DNA sequences localized in inactive replication units allowed amplification whereas those that have replicated will not be amplified by PCR. Using this sensitive and quantitative assay the replication kinetic analysis of a number of different DNA sequences can be performed from a single sorting experiment. PMID- 8341599 TI - Activation of HIV-specific ribozyme activity by self-cleavage. AB - A hammerhead ribozyme designed to cleave in trans the R region of HIV-1 RNA was inserted into a eukaryotic expression vector. This ribozyme was studied in vitro using the T3 RNA polymerase promoter located upstream of the eukaryotic promoter. The ribozyme showed no activity against its specific target sequence under any condition tested. To decrease the influence of potential cis inhibitory sequences in such a ribozyme transcript, a specific target sequence was inserted upstream of the ribozyme-coding sequence. This insertion allowed the release by cis cleavage of a short RNA bearing ribozyme activity and able to cleave in trans an external RNA target. The cis cleavage reaction generated two RNA molecules: the shorter RNA species, which included the catalytic domain, showed a trans cleavage reaction. This self-cleavable ribozyme was active in vitro at 37 degrees C against three distinct HIV-1 transcripts sharing the specific target sequence. Ribozyme activity was thus attained by self-cleavage of the ribozyme-containing sequence from the longer vector transcript. PMID- 8341601 TI - Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. AB - Differential display has been developed as a tool to detect and characterize altered gene expression in eukaryotic cells. The basic principle is to systematically amplify messenger RNAs and then distribute their 3' termini on a denaturing polyacrylamide gel. Here we provide methodological details and examine in depth the specificity, sensitivity and reproducibility of the method. We show that the number of anchored oligo-dT primers can be reduced from twelve to four that are degenerate at the penultimate base from the 3' end. We also demonstrate that using optimized conditions described here, multiple RNA samples from related cells can be displayed simultaneously. Therefore process-specific rather than cell-specific genes could be more accurately identified. These results enable further streamlining of the technique and make it readily applicable to a broad spectrum of biological systems. PMID- 8341600 TI - Interactions of USF and Ku antigen with a human DNA region containing a replication origin. AB - By means of a combination of ion-exchange and sequence-specific affinity chromatography techniques, we have purified to homogeneity two protein complexes binding in a human DNA region (B48) previously recognized to contain a DNA replication origin. The DNA sequence used for the protein purification (B48 binding site) contains a binding site for basic-helix-loop-helix DNA binding proteins. The first complex is composed of two polypeptides of 42- and 44-kDa; its size, heat stability, and target DNA sequence suggest that it corresponds to transcription factor USF; furthermore, the 42-kDa polypeptide is recognized by antibodies raised against 43-kDa-USF. The second complex is represented by equimolar amounts of two proteins of 72 and 87 kDa; microsequencing of the two species indicated that they correspond to the human Ku antigen. In analogy with Ku, they produce a regular pattern of footprints without an apparent sequence specificity, and their binding can be competed by unspecific DNA provided that it contains free ends. The potential role of B48 binding site and of these cognate proteins in origin activation is discussed. PMID- 8341602 TI - Self-cleavage activity of the genomic HDV ribozyme in the presence of various divalent metal ions. AB - To identify the divalent metal ions that can support the self-cleavage activity of the genomic ribozyme of human hepatitis delta virus (HDV), we tested the activity of various divalent metal ions in the ribozyme reactions catalyzed by HDV88 (683-770 nt) and 88DI3 (HDV88 with the sequence from 740-752 nt deleted). Among various metal ions tested, Mg2+, Mn2+, Ca2+ and Sr2+ efficiently supported the self-cleavage reactions of the HDV88 and 88DI3 ribozymes. In the case of the 88DI3 ribozyme, other divalent metal ions, such as Cd2+, Ba2+, Co2+, Pb2+ and Zn2+, were also able to support the self-cleavage reaction to some extent (< 10%). In the presence of spermidine (0.5 mM), the cleavage reaction was promoted at lower concentrations of effective divalent metal ions. The HDV ribozyme represents the only example of ribozyme to date of a ribozyme that catalyzes the self-cleavage reaction in the presence of Ca2+ ions as efficiently as it does in the presence of Mg2+ ions. PMID- 8341603 TI - Isolation, sequencing and overexpression of the gene encoding the theta subunit of DNA polymerase III holoenzyme. AB - The gene encoding the theta subunit of DNA polymerase III holoenzyme, designated holE, was isolated using a strategy in which peptide sequence was used to derive a DNA hybridization probe. Sequencing of the gene, which maps to 41.43 centisomes of the chromosome, revealed a 76-codon open reading frame predicted to produce a protein of 8,846 Da. When placed in a tac promoter expression vector, the open reading frame directed expression of a protein, that comigrated with authentic theta subunit from purified holoenzyme, to 6% of total soluble protein. PMID- 8341604 TI - DNA-protein interactions at the S.cerevisiae alpha 2 operator in vivo. AB - Two homodimeric proteins, alpha 2 and MCM1, are required to repress transcription of a-cell type specific genes in haploid yeast alpha-cells. In vitro studies by others of the interactions of these proteins with operator DNA have suggested that MCM1 binds to the middle and alpha 2 to the ends of the 31 bp operator. We have previously shown that alpha 2 organizes chromatin structure adjacent to the operator; in the presence of alpha 2 repressor, a precisely positioned nucleosome abuts the operator in both minichromosomes and the genome. We present in vivo footprinting evidence consistent with occupancy of the operator by MCM1 in both a and alpha-cells and by alpha 2 repressor in alpha-cells. Interestingly, our in vivo results differ from previous in vitro work in detail. In contrast to the broad block of reagent accessibility to DNA by the factors seen in vitro, we find a pattern of strand-specific protection or augmented reactivity in vivo. The in vivo results are consistent with genetic data concerning transcriptional regulation of a-cell specific genes and corroborate the crystallographic data of others. PMID- 8341605 TI - The importance of downstream delta-factor binding elements for the activity of the rpL32 promoter. AB - A salient feature of mammalian ribosomal protein genes is the location of promoter elements downstream, as well as upstream, of the transcriptional start point. Previous functional studies of the mouse rpL32 gene (Chung and Perry, Mol. Cell. Biol. 9, 2075; 1989) indicated that the first intron of this gene contains such an element. We show here that this element encompasses a binding site for a zinc finger nuclear protein known as delta (YY-1, muE1, UCRBP). The intronic delta site (delta i) is located 32 bp downstream of another delta site in the first exon (delta e). Transfection experiments with genes containing deleterious mutations in one or both delta sites or having alterations in the spacing between the sites indicate that the two delta elements function independently and contribute additively to the overall strength of the rpL32 promoter. Moreover, the contribution of the delta i element is the same whether it is oriented parallel or antiparallel to the delta e element. Together, the two delta elements raise the expression level about 10-fold over that attained by the upstream and initiator portions of the promoter. The positive role of the delta factor in rpL32 expression contrasts strikingly with its repressive role in various other genes. PMID- 8341606 TI - Primary structure of Trichoderma harzianum ribosomal protein L32. PMID- 8341607 TI - Isolation of CENIX and CENXII from Saccharomyces cerevisiae. PMID- 8341608 TI - Nucleotide sequence of the Schizosaccharomyces pombe 25S ribosomal RNA and its phylogenetic implications. PMID- 8341609 TI - Nucleotide sequence of the Borrelia burgdorferi dnaN gene encoding the beta subunit of DNA polymerase III. PMID- 8341610 TI - Capsid protein gene sequences of four tobacco mosaic virus strains defective for virus assembly. PMID- 8341611 TI - Nucleotide sequence of Salmonella bacteriophage P22 head completion genes 10 and 26. PMID- 8341612 TI - Nucleotide sequence of Mycobacterium leprae elongation factor (EF-Tu) gene. PMID- 8341613 TI - Midiprep method for isolation of DNA from plants with a high content of polyphenolics. PMID- 8341614 TI - A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. PMID- 8341615 TI - Fluorescence-based DNA sequencing with hexamer primers. PMID- 8341616 TI - Rapid sequencing of unpurified PCR products by thermal asymmetric PCR cycle sequencing using unlabeled sequencing primers. PMID- 8341617 TI - An EMSA-based method for determining the molecular weight of a protein--DNA complex. PMID- 8341619 TI - Gonorrhea. Finding and treating a moving target. AB - Gonorrhea is the most common reportable disease in the United States. In recent years, the epidemiology of this infection has changed as a result of increasing drug abuse, exchange of money and drugs for sex, and sexual promiscuity among teenagers, particularly blacks. Significant numbers of asymptomatic male carriers have been identified, which presents an additional challenge to disease control. Gonococcal infection has become increasingly resistant to traditional antibiotic therapy and now requires the use of newer, more expensive agents. Single-dose oral treatment with cefixime (Suprax) or a quinolone appears to be effective, safe, and practical for patients with uncomplicated gonorrhea. Serious infection and new syndromes caused by gonococci continue to be reported. Because disseminated infections can be fatal, hospitalization and treatment with intravenous antibiotics such as ceftriaxone sodium (Rocephin) or cefotaxime sodium (Claforan) are required. PMID- 8341618 TI - Simplified high throughput protocol for northern hybridization. PMID- 8341620 TI - Scary quotes about healthcare that may go down in history. PMID- 8341621 TI - Chronic obstructive pulmonary disease. Major objectives of management. AB - The successful management of chronic obstructive pulmonary disease (COPD) depends on achieving three major goals: reduction of airflow obstruction, prevention or management of complications, and improvement in the patient's quality of life. Exercise training is effective in improving the patient's performance; breathing training and education regarding smoking cessation and use of a peak flow meter are also vital to management. Some COPD patients may be suitable candidates for long-term oxygen therapy. PMID- 8341622 TI - Popliteal artery aneurysm. Prompt intervention prevents tragic consequences. AB - Popliteal artery aneurysm is an important, if uncommon, cause of lower extremity ischemia. About half of cases are asymptomatic. Untreated aneurysms may lead to embolization, rupture, thrombosis, and amputation. Diagnosis involves careful physical examination and use of ultrasound and arteriography. Prompt surgical intervention is essential. PMID- 8341623 TI - Modern coronary rehabilitation. New concepts in care. AB - Contemporary rehabilitative care for coronary patients involves individualized recommendations and applications. The challenge to the physician is to select those services that are appropriate for a given patient, on the basis of both medical recommendations and patient preferences, so as to encourage progressive independence in rehabilitative care. The physician, patient, and rehabilitation professional can then define the desired outcome of each intervention, in both a quantitative and a time-based format. Physical activity goals can often be rapidly met, whereas risk reduction addresses longer-term outcomes. Exercise test based risk stratification can identify the high-risk subset of coronary patients, who require supervision of exercise testing, often with ECG monitoring. Low-risk patients can exercise independently. Modest-intensity dynamic exercise is beneficial and has greater adherence and safety than high-intensity exercise. Isometric exercise is recommended once patients attain a reasonable dynamic (aerobic) exercise capacity. Education and counseling are necessary to implement reduction of coronary risk factors. Technological advances that may help in delivery of educational services include videocassettes and computer interactive programs for home use. Information shared with family members has added benefit, because they may also have coronary risk attributes. Innovative approaches may improve the effectiveness and efficiency of long-term rehabilitative care. PMID- 8341624 TI - Systolic hypertension in the elderly. Safe treatment with low-dose thiazide diuretics. AB - Low doses of thiazide diuretics are effective in controlling isolated systolic hypertension in most elderly patients. These agents are well tolerated and do not appear to adversely affect quality of life. Biochemical adverse effects are minimal with low doses. Of greatest importance, thiazide diuretics are the only class of antihypertensives that has been shown to reduce risk of cardiovascular events in patients with isolated systolic hypertension. Recent studies showed all these advantages with both chlorthalidone and hydrochlorothiazide therapy, although low-dose hydrochlorothiazide may cause less hypokalemia in the elderly than does chlorthalidone. PMID- 8341625 TI - Entrapment neuropathies. A guide to avoiding misdiagnoses. AB - Nerve entrapment has many possible causes and can mimic a broad range of disorders. A carefully taken history and thorough neurologic examination are the most important parts of evaluation, and plain radiography, electromyography, and nerve conduction velocity studies are useful adjuncts. Treatment options include correction of underlying causes; reduction in activity; exercise programs; wearing of splints, arch supports, or foot braces; local injections of corticosteroids and/or anesthetics; use of nonsteroidal anti-inflammatory drugs; and surgical decompression. Early, appropriate therapy ensures a good outcome. PMID- 8341626 TI - The antinuclear antibody test. When is a positive result clinically relevant? AB - The antinuclear antibody (ANA) test is sensitive but not specific. Many nonrheumatic diseases and conditions can cause positive results, and some healthy persons have positive results. ANA testing should not be used to evaluate patients who have vague complaints or symptoms. Rather, it is best used in patients with signs or symptoms of rheumatic disease to justify further specific investigation aimed at confirming a diagnosis. PMID- 8341627 TI - Acute gouty arthritis. Modern approaches to an ancient disease. AB - The principles governing the pathogenesis and treatment of gout have been established with greater clarity than those for almost any other rheumatic disease. The benefits of treatment include the virtual cure of a disabling and deforming disease. Adherence to proper management guidelines provides predictable relief of symptoms for patients and great satisfaction for the treating physician. PMID- 8341628 TI - Invasion of the 'killer' bees. Separating fact from fiction. AB - Even a single honeybee sting can lead to anaphylaxis in a susceptible person, but severe reactions can result from multiple stings, particularly if stings are from the fast-spreading Africanized honeybees, sometimes called "killer" bees. Signs and symptoms of multiple stings may include urticaria, nausea, vomiting, diarrhea, hypotension, confusion, seizures, and renal failure. Treatment is entirely supportive and requires special attention to airway patency, blood pressure, and renal function. Patients with more than 50 stings are at a higher risk of toxicity. Stingers should be removed by scraping gently to prevent further venom injection. Smoke or aerosolized deet (diethyl-toluamide) may thwart attacking bees, but avoidance is the best line of defense. PMID- 8341629 TI - Cytogenetic analysis of human oocytes after subzonal insemination. AB - Subzonal insemination has been proposed to achieve fertilization in cases where standard in vitro fertilization has failed. We present the results of chromosome analysis of oocytes after subzonal insemination. Our data suggest that the main cause (76 per cent) of the absence of cleavage after subzonal insemination is the total absence of sperm nucleus evolution of the injected spermatozoa. Our results also suggest that spermatozoa chromatin development is normal after subzonal insemination. Aneuploidy does not seem to be increased in zygotes after subzonal insemination. However, polyploidy was often more important than predicted by the observation of pronuclei (PN). Pronucleus development might be asynchronous and can appear earlier or later than after standard IVF. The cytogenetic risk after subzonal insemination might therefore be triploidy (if a triploid egg is transferred, because only 2 PN were seen) rather than aneuploidy or structural abnormalities. PMID- 8341630 TI - Applicability of DNA isolated from syncytiotrophoblast vesicles to gene amplification and molecular analysis. AB - Maternal contamination of fetal DNA represents a major problem when highly sensitive molecular techniques are used in the prenatal diagnosis of genetic diseases. For this reason, we have studied the possibility of using DNA isolated from syncytiotrophoblast vesicles as a target of gene amplification (PCR). Three PCR systems were selected which included a repetitive 149 bp fragment of the Y chromosome, the VNTR locus D1S80, and a portion of the beta-globin gene. The results of these experiments indicate that DNA isolated from syncytiotrophoblast vesicles is free of maternal contamination and is suitable for gene amplification and DNA analysis. PMID- 8341631 TI - Grief and mid-trimester fetal loss. AB - Fetal loss through miscarriage or termination of pregnancy for genetic reasons often provokes the grief of bereavement. This is not fully understood, and the extent of the distress is often underestimated by professionals and family alike. We have examined elements of the normal bereavement process and have found that they may occur in specific and accentuated forms in mid-trimester fetal loss. We discuss our findings in the light of the attachment theory--a psychodynamic model for understanding grief reactions. PMID- 8341632 TI - Rapid karyotyping in ectopic pregnancies. AB - The aim of this study was to determine the feasibility of karyotyping ectopic Fallopian tube pregnancies utilizing dividing cytotrophoblast cells. Villi from 78 ectopic conceptuses were processed by the direct chromosome technique and cytogenetic diagnosis was successful in 60 cases (76.9 per cent). The amount of villi obtained, as well as villus morphology, was correlated with cytogenetic success rate. Histological examination of the Fallopian tube was also carried out. A total of 47 cases were chromosomally abnormal (78.3 per cent), which is the highest frequency of cytogenetic abnormalities reported to date. PMID- 8341633 TI - Characterization of i(18p) in prenatal diagnosis by fluorescence in situ hybridization. AB - A case is presented in which chorionic villus direct preparation and cultured chorionic villus cells revealed a 47,XX+mar karyotype. The marker was a small metacentric chromosome and appeared to be i(18p)--isochromosome 18p. Follow-up studies in both amniotic fluid and fetal fibroblasts confirmed the karyotype. In order to characterize the marker, a panel of biotinylated DNA probes was used, including a whole chromosome 18 probe, chromosome 18-specific alpha satellite DNA, Yac clones, and a pan-telomeric probe. These studies show that the marker is a monocentric i(18p) in which about 80 per cent of chromosome 18 alpha satellite DNA has been lost. PMID- 8341634 TI - False-positive amniotic fluid acetylcholinesterase analysis in the third trimester. AB - Thirty-two third-trimester amniotic fluid samples were studied according to the indication for amniocentesis, result of acetylcholinesterase (AChE) analysis, and outcome, in order to address the issue of the effectiveness of AChE testing late in gestation. The results indicate that third-trimester AChE analysis is less effective than second trimester in distinguishing open neural tube defects (ONTDs) and ventral wall defects (VWDs) from other abnormalities. False-positive results occurred in cases of isolated hydrocephaly (four of seven cases), polyhydramnios, and intrauterine growth retardation (IUGR). Caution is recommended in interpreting third-trimester AChE tests, particularly when neither an ONTD nor a VWD is observed by ultrasound. PMID- 8341635 TI - First-trimester diagnosis of duodenal stenosis associated with oesophageal atresia. AB - Duodenal stenosis associated with oesophageal atresia was diagnosed by ultrasound at 12 weeks' gestation. The diagnosis was made by recognition of a double bubble sign which was more pronounced when a vaginal transducer was used. Post-abortion autopsy confirmed the diagnosis. Oesophageal and duodenal obstruction in this case had no effect on the amount of amniotic fluid or the alpha-fetoprotein concentration since swallowing and subsequent utilization of amniotic fluid do not occur before 12 weeks of gestation. PMID- 8341636 TI - A large retinoblastoma detected in a fetus at 21 weeks of gestation. AB - The facial tumour described here is the first reported case of a large retinoblastoma detected early in pregnancy and adds another item to the differential diagnosis of facial tumours visualized by prenatal ultrasound examination. Ultrasound examination of the fetal eyes can be offered in cases of retinoblastomas where prenatal DNA diagnosis is otherwise impossible. PMID- 8341637 TI - Molecular cytogenetic characterization of marker chromosomes found at prenatal diagnosis. AB - The nature and origin of two de novo small marker chromosomes found at prenatal diagnosis were determined by fluorescence in situ hybridization using chromosome centromere-specific probes and chromosome-specific plasmid libraries. One marker was found in a mosaic state and was shown to be an i(18p). The second marker was characterized as an inv dup(22). We conclude that molecular cytogenetic analysis contributes to the identification of marker chromosomes and therefore facilitates genetic counselling and decision-making for the parents. PMID- 8341638 TI - Ultrasonographic features in a case of heterozygous achondroplasia at 25 weeks' gestation. AB - Prenatal diagnosis of heterozygous achondroplasia at 25 weeks is described. First level fetal ultrasonography demonstrated short long bones of the lower limbs. Second-level examination showed a large head; shortened femur, fibula, and tibia; a 'trident'-shaped hand; and an abnormal facial profile. PMID- 8341639 TI - Prenatal diagnosis of isolated bilateral microphthalmia with confirmation by evaluation of products of conception obtained by dilation and evacuation. AB - We describe the prenatal diagnosis of isolated bilateral fetal microphthalmia in a woman at increased risk of having a fetus with microphthalmia. Ultrasound examinations at 16.1 and 19.5 weeks' gestation demonstrated bilateral fetal microphthalmia with no other associated structural defects. The patient elected to terminate her pregnancy at 19.5 weeks. Pathological evaluation of the products of conception obtained by dilation and evacuation confirmed the prenatal diagnosis of isolated bilateral fetal microphthalmia. PMID- 8341640 TI - Early prenatal sonographic diagnosis of neuropathic arthrogryposis multiplex congenita with osseous heterotopia. AB - A prenatal diagnosis of arthrogryposis multiplex congenita (AMC) has been carried out on a 19-week-old fetus by means of echography. The ultrasonographic characteristics were unnatural position of the four limbs associated with articular anomalies together with absence of active fetal movements. A therapeutic interruption of pregnancy was performed and the diagnosis was confirmed. At autopsy, architectural disorder of the motor neurons of the anterior medullary horn revealed a neuropathic pathogenesis of the arthrogryposis. Moreover, at the lumbar level the spinal cord was progressively replaced by heterotopic bony tissue which caused a more severe deformity of the lower limbs compared with the upper. The aspects of anatomo-pathological, genetic, and differential diagnosis are discussed showing the precocity of the prenatal diagnosis and the peculiarity of the aetiology of our case. PMID- 8341641 TI - Prenatal diagnosis of exencephaly. AB - This paper presents a sonographic diagnosis of exencephaly made during the last trimester of gestation. The sonogram showed the absence of bones in the cranial vault together with the presence of a disorganized cerebral mass, with loss of its normal anatomy. Post-partum examination of the newborn confirmed the findings of the sonogram. We briefly review the characteristics of exencephaly, its aetiology, and its relationship to anencephaly. PMID- 8341642 TI - Direct selection of antibodies that coordinate metals from semisynthetic combinatorial libraries. AB - An iterative strategy for the selection of catalytic metalloantibodies is described. The first stage of this strategy is validated by the selection of semisynthetic antibodies that coordinate a variety of different metal ions and the metal oxide magnetite. These results have implications not only for the development of catalytic metalloantibodies but also for the development of reagents for magnetic resonance imaging, delivery of radioisotopes, and purification of recombinant proteins. PMID- 8341643 TI - Targeting the site of RNA-RNA recombination in brome mosaic virus with antisense sequences. AB - It has been postulated that local hybridizations between viral RNAs can mediate recombination in brome mosaic virus (BMV) and in poliovirus. To test this model, a 3' fragment of BMV RNA1 was inserted into the 3' noncoding sequence of BMV RNA3 in an antisense orientation. This resulted in high-frequency nonhomologous crossovers at or near the hybridized region. Insertion of the same RNA1 fragment in a positive-sense orientation did not promote recombination. Modification of the antisense insert by deletion of 3' portions did not affect the sites of crossover. However, modification of the 5' portion shifted the crossovers toward the central part of the heteroduplex region. Our results provide experimental evidence that recombinant crosses can be primed by hybridization between viral RNA molecules. PMID- 8341644 TI - Inhibition of type 1 human immunodeficiency virus replication by a tat antagonist to which the virus remains sensitive after prolonged exposure in vitro. AB - The transactivator of transcription, Tat, of human immunodeficiency virus type 1 (HIV-1) is required for viral replication. Inhibition of Tat function could have the potential to keep integrated provirus in dormancy. In the presence of Tat, Ro 24-7429, an analog of Ro 5-3335, inhibited expression of indicator genes controlled by the HIV-1 long terminal repeat promoter in transient transfection assays and in a constitutive cell line at noncytotoxic concentrations. Reduction of steady-state mRNA of the indicator gene by the compound correlated with reduction of the gene product in the constitutive cell line. Ro 24-7429 has broad activity against several strains of HIV-1 in different cell lines, peripheral blood lymphocytes, and macrophages (IC90 = 1-3 microM). Importantly, Ro 24-7429 inhibited viral replication in both acute and chronic infection in vitro, a characteristic expected of a Tat antagonist and not shared by viral reverse transcriptase inhibitors. Consistent with this, the compound reduced cell associated viral RNA and proteins and partially restored cell-surface CD4 in chronically infected cells. After 2 years of continued weekly passage of the virus in fresh CEM cells grown in the presence of the compound at 1 or 10 microM, the virus did not develop resistance to the drug. These results indicate that the compound's action might involve a cellular factor. PMID- 8341645 TI - Treatment of chronic-relapsing experimental autoimmune encephalomyelitis with the synthetic immunomodulator linomide (quinoline-3-carboxamide). AB - Linomide is a synthetic immunomodulator that enhances natural killer cell activity and significantly activates several lymphocytic cell subpopulations in both experimental animals and humans. In this study we examined the effect of linomide (80 mg per kg per day in drinking water) on mice with chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE), a T-cell-mediated organ specific autoimmune disease that resembles human multiple sclerosis. None of the mice (n = 17) that were treated with linomide from day 7 after disease induction developed any clinical or histopathological signs of CR-EAE, as compared to 19 of 20 untreated controls that were severely paralyzed and had extensive demyelinating lesions in the central nervous system. Linomide-treated animals were also resistant to an induced attack by a booster injection with a murine spinal cord homogenate. When administered to mice exhibiting severe clinical signs of paralysis, linomide inhibited both spontaneous and induced relapses. Linomide treatment protected mice from passively induced CR-EAE as well, when given from the day of injection with myelin-basic-protein-specific lymphocytes. Lymphocytes obtained from linomide-treated mice had a reduced in vitro proliferative response to the myelin basic protein and to the tuberculin purified protein derivative, whereas the mitogenic response to concanavalin A was not affected. Natural killer cell and lymphokine-activated killer cell activities were enhanced. These results suggest that linomide regulates autoimmunity in the absence of systemic immunosuppression. Since linomide is very well tolerated in experimental animals and humans, it might be used in the treatment of multiple sclerosis. PMID- 8341646 TI - Kinetics of human immunodeficiency virus type 1 (HIV-1) DNA and RNA synthesis during primary HIV-1 infection. AB - HIV-1 replication and viral burden in peripheral blood mononuclear cells (PBMC) have been reported to be high in primary infection but generally very low during the prolonged period of clinical latency. It is uncertain precisely when this transition occurs during the HIV-1 infection and what the relationship is between the changes in HIV-1 replication versus the clearance of infected cells in the overall control of viral replication. In the present study, the kinetics of viral burden (i.e., frequency of HIV-1-infected cells) and replication during primary and early-chronic infection were analyzed in PBMC of four acutely infected individuals. High frequencies of HIV-1-infected cells and high levels of virus replication were observed in PBMC after primary HIV-1 infection. Down-regulation of virus replication in PBMC was observed in all four patients coincident with the emergence of HIV-1-specific immune responses. Other parameters of virus replication, such as circulating plasma p24 antigen and plasma viremia showed similar kinetics. In contrast, a significant decline in viral burden in PBMC was observed in only one of four patients. These results indicate that the down regulation in the levels of virus replication associated with the clinical transition from acute to chronic infection does not necessarily reflect a reduction in viral burden, thus suggesting the involvement of additional factors. Identification of these factors will be important in elucidating the host mechanisms involved in the early control of HIV-1 infection and disease. PMID- 8341647 TI - Neurexin III alpha: extensive alternative splicing generates membrane-bound and soluble forms. AB - The structure of neurexin III alpha was elucidated from overlapping cDNA clones. Neurexin III alpha is highly homologous to neurexins I alpha and II alpha and shares with them a distinctive domain structure that resembles a cell surface receptor. cDNA cloning and PCR experiments revealed alternative splicing at four positions in the mRNA for neurexin III alpha. Alternative splicing was previously observed at the same positions in either neurexin I alpha or neurexin II alpha or both, suggesting that the three neurexins are subject to extensive alternative splicing. This results in hundreds of different neurexins with variations in small sequences at similar positions in the proteins. The most extensive alternative splicing of neurexin III alpha was detected at its C-terminal site, which exhibits a minimum of 12 variants. Some of the alternatively spliced sequences at this position contain in-frame stop codons, suggesting the synthesis of secreted proteins. None of the sequences of the other splice sites in this or the other two neurexins include stop codons. RNA blot analysis demonstrate that neurexin III alpha is expressed in a brain-specific pattern. Our results suggest that the neurexins constitute a large family of polymorphic cell surface proteins that includes secreted variants, indicating a possible role as signaling molecules. PMID- 8341648 TI - Preferential and asymmetric interaction of linker histones with 5S DNA in the nucleosome. AB - We establish that linker histones H1 and H5 bind preferentially to a Xenopus borealis somatic 5S RNA gene associated with an octamer of core histones rather than to naked 5S DNA. This preferential binding requires free linker DNA to either side of the nucleosome core. Incorporation of a single linker histone molecule into the nucleosome protects an additional 20 bp of linker DNA from micrococcal nuclease digestion. This additional DNA is asymmetrically distributed with respect to the nucleosome core. Incorporation of linker histones causes no change to the cleavage of DNA in the nucleosome by hydroxyl radical or DNase I. PMID- 8341649 TI - An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. AB - The human lymphoblastoid MT1 B-cell line was previously isolated as one of a series of mutant cells able to survive the cytotoxic effects of N-methyl-N'-nitro N-nitrosoguanidine (MNNG). MT1 cells nevertheless remain sensitive to mutagenesis by MNNG and display a mutator phenotype. These phenotypes have been attributed to a single genetic alteration postulated to confer a defect in strand-specific mismatch repair, a proposal that attributes the cytotoxic effect of DNA alkylation in wild-type cells to futile attempts to correct mispairs that arise during replication of alkylated template strands. Our results support this view. MNNG-induced mutations in the HPRT gene of MT1 cells are almost exclusively G.C- >A.T transitions, while spontaneous mutations observed in this mutator cell line are single-nucleotide insertions, transversions, and A.T-->G.C transitions. In vitro assay has demonstrated that the MT1 line is in fact deficient in strand specific correction of all eight base-base mispairs. This defect, which is manifest at or prior to the excision stage of the reaction, is due to simple deficiency of a required activity because MT1 nuclear extracts can be complemented by a partially purified HeLa fraction to restore in vitro repair. These findings substantiate the idea that strand-specific mismatch repair contributes to alkylation-induced cytotoxicity and imply that this process serves as a barrier to spontaneous transition, transversion, and insertion/deletion mutations in mammalian cells. PMID- 8341650 TI - Differentiation and characterization of B-cell precursors detected in the yolk sac and embryo body of embryos beginning at the 10- to 12-somite stage. AB - The embryonic sites in which progenitors of the hematopoietic lineages first emerge are ideal regions to characterize both the cells and environment needed to initiate blood cell development. For a number of years both the murine yolk sac and embryo have been recognized to contain progenitors of B lymphocytes. However, clonal, quantitative in vitro assays, which allow precise observation of precursors and their progeny, have been lacking. Moreover, the site of origin of the initial events remains controversial. In this report we document the presence of B-cell progenitors in yolk sac and embryonic tissue obtained from mouse fetuses beginning at the 10-somite stage, day 8.5. We determine the frequency, cell-surface phenotype, and growth properties of these progenitors. We show that these cells can differentiate into immunoglobulin-secreting cells and that the progeny derived from single progenitors are diverse with respect to immunoglobulin heavy-chain allotype expression, diversity-joining region use, and heavy-chain variable-region utilization. PMID- 8341651 TI - Lipid advanced glycosylation: pathway for lipid oxidation in vivo. AB - To address potential mechanisms for oxidative modification of lipids in vivo, we investigated the possibility that phospholipids react directly with glucose to form advanced glycosylation end products (AGEs) that then initiate lipid oxidation. Phospholipid-linked AGEs formed readily in vitro, mimicking the absorbance, fluorescence, and immunochemical properties of AGEs that result from advanced glycosylation of proteins. Oxidation of unsaturated fatty acid residues, as assessed by reactive aldehyde formation, occurred at a rate that paralleled the rate of lipid advanced glycosylation. Aminoguanidine, an agent that prevents protein advanced glycosylation, inhibited both lipid advanced glycosylation and oxidative modification. Incubation of low density lipoprotein (LDL) with glucose produced AGE moieties that were attached to both the lipid and the apoprotein components. Oxidized LDL formed concomitantly with AGE-modified LDL. Of significance, AGE ELISA analysis of LDL specimens isolated from diabetic individuals revealed increased levels of both apoprotein- and lipid-linked AGEs when compared to specimens obtained from normal, nondiabetic controls. Circulating levels of oxidized LDL were elevated in diabetic patients and correlated significantly with lipid AGE levels. These data support the concept that AGE oxidation plays an important and perhaps primary role in initiating lipid oxidation in vivo. PMID- 8341652 TI - Neuronal colocalization of mRNAs for neurotrophins and their receptors in the developing central nervous system suggests a potential for autocrine interactions. AB - Development and survival of neurons in the central nervous system are dependent on the activity of a variety of endogenous neurotrophic agents. Using combined isotopic and nonisotopic in situ hybridization histochemistry, we have found that subsets of neurons within the developing forebrain coexpress the mRNAs for both neurotrophins (nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3) and their receptors (p75NGFR, TrkA, and TrkB). The colocalization of mRNA for neurotrophin receptors and their ligands in presumptive neurotrophin target neurons suggests the potential for autocrine and paracrine mechanisms of action during development. Such mechanisms may ensure the onset of differentiation and survival of specific subsets of neurons prior to and following target innervation. PMID- 8341654 TI - Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene. AB - Inappropriate expression of the Evi-1 zinc-finger gene in hematopoietic cells has been associated with acute myelogenous leukemia and myelodysplastic syndromes in murine models and in humans. Consistent with this, previous studies have shown that aberrant expression of the Evi-1 gene in a myeloid progenitor cell line blocks granulocytic differentiation. Here we demonstrate that the aberrant expression of the Evi-1 gene impairs the normal response of erythroid cells or bone-marrow progenitors to erythropoietin. Erythroid differentiation has been shown to require the GATA-1 transcription factor that binds to a sequence contained within the consensus binding sequence identified for Evi-1. In the studies presented here we also show that Evi-1 can repress GATA-1-dependent transactivation in transient chloramphenicol acetyltransferase assays. Together the data support the hypothesis that inappropriate expression of the Evi-1 gene blocks erythropoiesis by repressing the transcription of a subset of GATA-1 target genes. PMID- 8341653 TI - "Diabodies": small bivalent and bispecific antibody fragments. AB - Bivalent and bispecific antibodies and their fragments have immense potential for practical application. Here we describe the design of small antibody fragments with two antigen-binding sites. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) on the same polypeptide chain (VH-VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. As indicated by a computer graphic model of the dimers, the two pairs of domains can pack together with the antigen-binding sites pointing in opposite directions. The dimeric antibody fragments, or "diabodies," can be designed for bivalent or bispecific interactions. Starting from the monoclonal antibodies NQ11.7.22 (NQ11) and D1.3 directed against the hapten phenyloxazolone and hen egg lysozyme, respectively, we built bivalent fragments (VHNQ11-VLNQ11)2 and (VHD1.3-VLD1.3)2 and bispecific fragments VHNQ11-VLD1.3 and VHD1.3-VLNQ11. The fragments were expressed by secretion from bacteria and shown to bind specifically to the hapten and/or antigen. Those with 5- and 15-residue linkers had similar binding affinities to the parent antibodies, but a fragment with the VH domain joined directly to the VL domain was found to have slower dissociation kinetics and an improved affinity for hapten. Diabodies offer a ready means of constructing small bivalent and bispecific antibody fragments in bacteria. PMID- 8341655 TI - Cell cycle regulation of nuclear localization of hepatitis B virus core protein. AB - The hepatitis B virus (HBV) core protein has been found in the nucleus, the cytoplasm, or both of HBV-infected hepatocytes. However, the mechanism that regulates the subcellular localization of the HBV core protein is still unclear. In this report, we demonstrate that nuclear localization of the HBV core protein is cell cycle-regulated in two different cell lines. The amount of the core protein in the nucleus was increased during the G1 phase, reduced to an undetectable level during the S phase, and increased again when the cells were confluent and ceased to grow. Thus, the nuclear localization of the core protein during HBV infection can be at least partially attributed to liver injury and regeneration, which cause the hepatocytes to enter cell cycles. Based on the observation that the cytoplasmic core protein was phosphorylated and the nuclear core protein was not, we speculate that nuclear localization of the HBV core protein is negatively regulated by phosphorylation during the cell cycle. PMID- 8341656 TI - Anti-cardiolipin antibodies induce pregnancy failure by impairing embryonic implantation. AB - The antiphospholipid syndrome is characterized by thrombocytopenia, thrombosis, and recurrent fetal loss in association with anti-cardiolipin antibodies (ACAs) or lupus anti-coagulants. However, the causal role of these antibodies in the disease and the mechanisms by which the ACA may induce the syndrome are not clear. Recently, we have established an experimental mouse antiphospholipid syndrome induced by the mouse IgM monoclonal ACA designated 2C4C2. In the present study, we focused on the effects of immunization with the monoclonal ACA 2C4C2 on the outcome of pregnancies in BALB/c female mice. Four weeks after active immunization with the monoclonal ACA, a severe gestational failure with low pregnancy rates, low number of fetuses, and a high rate of resorptions was observed. Moreover, embryos obtained from the ACA-immunized females on day 3.5 of pregnancy were severely impaired, demonstrating developmental delay and abnormal morphology. These abnormal embryos failed also to develop in an in vitro implantation model. Furthermore, specific binding of the 2C4C2 ACA to the trophectoderm cell lineage of in vitro implanting normal embryos was observed. Thus, our studies demonstrate that the severe ACA-induced gestational failure results from an impairment of implantation and suggest that the ACA may react directly with the preimplantation embryos. PMID- 8341657 TI - O6-methylguanine-DNA methyltransferase protects against nitrosamine-induced hepatocarcinogenesis. AB - We previously generated transgenic C3H/HeN mice by introducing the Escherichia coli O6-methylguanine-DNA methyltransferase (MGMT, DNA-O6-methylguanine:protein-L cysteine S-methyltransferase, EC2.1.1.63) gene, ada, attached to the Chinese hamster metallothionein I gene promoter. One transgenic mouse line expressing both ada-specific mRNA and Ada protein could be propagated over many generations in a homozygous state with respect to the integrated DNA. Liver extracts from transgenic homozygous mice have consistently demonstrated about 3 times the control activity of normal mice. Furthermore, in the transgenic homozygotes treated with ZnSO4, activity is increased to 6-8 times the normal level in mice and is equivalent to that for man. To examine whether these increased levels of MGMT activity can actually decrease the susceptibility of animals to N-nitroso compounds, we studied liver carcinogenesis in our transgenic mice expressing high amounts of MGMT. Groups of transgenic and nontransgenic mice, each comprising about 200 suckling animals (14 +/- 1 days old), were divided each into eight subgroups, providing paired groups of transgenic and nontransgenic mice. They received an i.p. injection of ZnSO4 to induce MGMT, and 10 hr thereafter were given an i.p. injection of either dimethylnitrosamine or diethylnitrosamine. Liver tumor development was quantitatively assessed at 7-11 months. Here, we report statistically significant reduction of tumor formation in transgenic mice of four of the six paired groups that received treatment. The remaining two demonstrated results in line with dose dependence. Therefore, our data indicate that MGMT can indeed protect animals from low-dose exposure to environmental alkylating carcinogens. PMID- 8341658 TI - Yersinia enterocolitica invasin: a primary role in the initiation of infection. AB - The ability to invade the intestinal epithelium of mammals is an essential virulence determinant of Yersinia enterocolitica. The chromosomally encoded Y. enterocolitica 8081v invasion gene, inv, was disrupted to assess its role in pathogenesis. The inv mutant (JP273v) was approximately 80-fold less invasive than wild type for cultured epithelial cells. When mice were infected intragastrically, up to 10(7) fewer JP273v were recovered from Peyer's patches early (6-18 hr) after infection compared with wild type. Analysis of the course of infection revealed that the inv mutant had distinct differences relative to wild type in the distribution of visible infectious foci and in tissue colonization; however, the mutant and wild-type strains had similar LD50 values for both orally and intraperitoneally infected mice. The invasion defect of the inv mutant was fully complemented in vitro and in vivo by introduction of the wild-type inv gene in trans. The inv gene product, invasin, appears to play a vital role in promoting entry during the initial stage of infection. During the subsequent establishment of a systemic infection, invasin may be of secondary importance, since the Y. enterocolitica inv mutant was as proficient as wild type at causing a fatal infection in mice. Based on these data, we discuss the role of invasin in a naturally occurring Y. enterocolitica infection. PMID- 8341659 TI - Volatile anesthetics compete for common binding sites on bovine serum albumin: a 19F-NMR study. AB - There is controversy as to the molecular nature of volatile anesthetic target sites. One proposal is that volatile anesthetics bind directly to hydrophobic binding sites on certain sensitive target proteins. Consistent with this hypothesis, we have previously shown that a fluorinated volatile anesthetic, isoflurane, binds saturably [Kd (dissociation constant) = 1.4 +/- 0.2 mM, Bmax = 4.2 +/- 0.3 sites] to fatty acid-displaceable domains on serum albumin. In the current study, we used 19F-NMR T2 relaxation to examine whether other volatile anesthetics bind to the same sites on albumin and, if so, whether they vary in their affinity for these sites. We show that three other fluorinated volatile anesthetics bind with varying affinity to fatty acid-displaceable domains on serum albumin: halothane, Kd = 1.3 +/- 0.2 mM; methoxyflurane, Kd = 2.6 +/- 0.3 mM; and sevoflurane, Kd = 4.5 +/- 0.6 mM. These three anesthetics inhibit isoflurane binding in a competitive manner: halothane, K(i) (inhibition constant) = 1.3 +/- 0.2 mM; methoxyflurane, K(i) = 2.5 +/- 0.4 mM; and sevoflurane, K(i) = 5.4 +/- 0.7 mM--similar to each anesthetic's respective Kd of binding to fatty acid displaceable sites. These results illustrate that a variety of volatile anesthetics can compete for binding to specific sites on a protein. PMID- 8341660 TI - Kinetic control of Ca(II) signaling: tuning the ion dissociation rates of EF-hand Ca(II) binding sites. AB - EF-hand Ca(II) binding sites share a conserved architecture and are prevalent in Ca(II) signaling pathways. The ion binding kinetics of these sites are carefully tuned to provide the physiologically appropriate activation and inactivation time scales. Here we examine kinetic tuning by the side chain at the ninth position of the EF-loop. A model is proposed in which both the size and charge of the side chain contribute to kinetic tuning. To test this model, the ninth loop position of the EF-hand-like site in the Escherichia coli D-galactose binding protein has been engineered and the Tb(III) dissociation kinetics of the resulting sites have been analyzed. Substitutions at this position are observed to generate up to 10(4)-fold changes in Tb(III) dissociation rates, with little effect on Tb(III) affinity. Furthermore, the observed pattern of rate changes confirm the model's predictions; long side chains at the ninth loop position yield slow dissociation kinetics as predicted for a steric block, whereas acidic side chains yield slow dissociation kinetics as expected for an electrostatic barrier. PMID- 8341661 TI - A general two-metal-ion mechanism for catalytic RNA. AB - A mechanism is proposed for the RNA-catalyzed reactions involved in RNA splicing and RNase P hydrolysis of precursor tRNA. The mechanism postulates that chemical catalysis is facilitated by two divalent metal ions 3.9 A apart, as in phosphoryl transfer reactions catalyzed by protein enzymes, such as the 3',5'-exonuclease of Escherichia coli DNA polymerase I. One metal ion activates the attacking water or sugar hydroxyl, while the other coordinates and stabilizes the oxyanion leaving group. Both ions act as Lewis acids and stabilize the expected pentacovalent transition state. The symmetry of a two-metal-ion catalytic site fits well with the known reaction pathway of group I self-splicing introns and can also be reconciled with emerging data on group II self-splicing introns, the spliceosome, and RNase P. The role of the RNA is to position the two catalytic metal ions and properly orient the substrates via three specific binding sites. PMID- 8341662 TI - Single kinesin molecules crossbridge microtubules in vitro. AB - Kinesin is a cytoplasmic motor protein that moves along microtubules and can induce microtubule bundling and sliding in vitro. To determine how kinesin mediates microtubule interactions, we determined the shapes and mass distributions of squid brain kinesin, taxol-stabilized microtubules (squid and bovine), and adenosine 5'-[beta, gamma-imido]triphosphate-stabilized kinesin microtubule complexes by high-resolution metal replication and by low temperature, low-dose dark-field scanning transmission electron microscopy of unfixed, directly frozen preparations. Mass mapping by electron microscopy revealed kinesins loosely attached to the carbon support as asymmetrical dumbbell shaped molecules, 40-52 nm long, with a mass of 379 +/- 15 kDa. The mass distribution and shape of these molecules suggest that these images represent kinesin in a shortened conformation. Kinesin-microtubule complexes were organized as bundles of linearly arrayed microtubules, stitched together at irregular intervals by cross-bridges typically < or = 25 nm long. The crossbridges had a mass of 360 +/- 15 kDa, consistent with one kinesin per crossbridge. These results suggest that kinesin has a second microtubule binding site in addition to the known site on the motor domain of the heavy chain; this second site may be located near the C terminus of the heavy chains or on the associated light chains. Thus, kinesin could play a role in either crosslinking or sliding microtubules. PMID- 8341663 TI - Short DNA sequences from the cytoplasm of mouse tumor cells induce immortalization of human lymphocytes in vitro. AB - Cytoplasts of mouse L929 and Ehrlich ascites tumor cells harbor DNA sequences that induce unlimited proliferation ("immortalization") of human lymphocytes after transfection in vitro. By equilibrium centrifugation of cytoplasmic lysates in a neutral CsCl gradient, the immortalizing activity was recovered together with extramitochondrial fractions at high salt densities (1.85-1.87 g/cm3). Unexpectedly, these fractions contain linear DNA molecules of 50-500 bp in length. In contrast, cytoplasts of primary, senescent cells (mouse embryo fibroblasts, human lymphocytes) do not harbor DNA in the corresponding fractions. Cytoplasmic DNA isolated from high-density fractions of mouse tumor cells was cloned in subset libraries, and of 45 DNA sequences we identified 2 clones--one from L929 cytoplasts (203 bp) and another one from the cytoplasm of Ehrlich ascites cells (372 bp)--that induce unlimited proliferation of human lymphocytes in vitro. Immortalized lymphoid cells harbor 1-5 copies of transfected DNA integrated into chromosomal DNA, whereas about 100 copies were found as episomal DNA in the cytoplasmic fraction. No immortalization could be induced by transfection of nuclear DNA randomly fragmented to 200-500 bp. Although the cloned DNA sedimented at 1.70 g/cm3, after transient transfection into lymphocytes, these DNA sequences form salt-stable complexes that sediment in fractions at the same high density (1.82-1.88 g/cm3) from which they were originally cloned. The high-density banding of these cytoplasmic DNA sequences may be due to association with RNA and/or with (metallo-) proteins in vivo. Since both cloned DNA sequences with immortalizing activity have stop codons for protein translation in all possible reading frames, immortalization may be induced by insertional inactivation or functional suppression of genes that are needed to be expressed during cellular senescence or programmed cell death. PMID- 8341665 TI - Milk and fat yields decline in bovine leukemia virus-infected Holstein cattle with persistent lymphocytosis. AB - Effects of bovine leukemia virus (BLV) infection on milk and fat yields were studied by using data collected from Holstein cows over a 6-year period. Milk and fat yields in BLV-infected cows with persistent lymphocytosis (PL) declined significantly relative to their BLV-infected non-PL herdmates. Declines were most pronounced in cows older than 6 years. The estimated loss to the dairy industry due to PL is more than $42 million annually. A major histocompatibility complex class I (BoLA-A) allele that has been previously associated with resistance to PL was associated with longevity and realization of milk production potentials, indicating that genetic resistance to PL will have an economic benefit in herds where BLV is endemic. PMID- 8341664 TI - Metastatic conversion of cells by expression of human papillomavirus type 16 E6 and E7 genes. AB - The human papillomavirus type 16 (HPV-16) is a DNA tumor virus highly associated with cervical carcinoma. Viral DNA from HPV-16 is found in primary tumors and their metastatic lesions. To investigate the role of HPV-16 oncoproteins in the development of cancer metastasis, the E6 and E7 genes from HPV-16 were inserted into retrovirus and introduced into nonmetastatic mouse cell lines. Expression of either of the viral genes from HPV-16 made the cells metastatic in nude mice. In contrast, expression of the E6 and E7 genes of HPV type 6 (HPV-6b), which is frequently found in nonmalignant HPV-associated diseases, did not. The metastatic ability of cells transduced with viral genes of HPV-16 did not correlate with their growth rate or sensitivity to destruction by natural killer cells. Our results demonstrate that expression of oncogenic proteins of HPV-16 can cause tumor metastasis and implicate HPV-16 in an important role regarding the progression of HPV-associated human cancers. PMID- 8341666 TI - Transmutation of a heme protein. AB - Residue Asn57 of bovine liver cytochrome b5 has been replaced with a cysteine residue, and the resulting variant has been isolated from recombinant Escherichia coli as a mixture of four major species: A, BI, BII, and C. A combination of electronic spectroscopy, 1H NMR spectroscopy, resonance Raman spectroscopy, electrospray mass spectrometry, and direct electrochemistry has been used to characterize these four major cytochrome derivatives. The red form A (E(m) = -19 mV) is found to possess a heme group bound covalently through a thioether linkage involving Cys57 and the alpha carbon of the heme 4-vinyl group. Form BI has a covalently bound heme group coupled through a thioether linkage involving the beta carbon of the heme 4-vinyl group. Form BII is similar to BI except that the sulfur involved in the thioether linkage is oxidized to a sulfoxide. The green form C (E(m) = 175 mV) possesses a noncovalently bound prosthetic group with spectroscopic properties characteristic of a chlorin. A mechanism is proposed for the generation of these derivatives, and the implications of these observations for the biosynthesis of cytochrome c and naturally occurring chlorin prosthetic groups are discussed. PMID- 8341667 TI - Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. AB - The human genome contains large regions that are highly structured. Sequence related members of multigene families are often found in a clustered organization. Here we describe a previously unrecognized gene cluster composed of genes coding for calcium-binding proteins of the S100 family. The linkage of six S100 genes was established by pulsed-field gel electrophoresis, and a contiguous DNA sequence of 15 kilobases containing the full coding region of four different S100 genes was characterized. This is the tightest mammalian gene cluster discovered so far to our knowledge. Two additional S100 genes are located within the cluster, both of which exhibit unique structural features when compared with other S100 genes. The product of S100E is cysteine-rich, whereas that of S100D contains a long hydrophobic N-terminal tail. The gene cluster was assigned to chromosome 1q21, one of the bands showing rearrangements in neoplasms at high frequency. The deregulated expression of some S100 genes in the cluster during tumor progression suggests that chromosomal abnormalities may influence the expression of S100 genes in late stages of cancer, particularly in association with the formation of metastases. PMID- 8341668 TI - Stimulus-induced dissociation of alpha subunits of heterotrimeric GTP-binding proteins from the cytoskeleton of human neutrophils. AB - Previous studies on the mechanism responsible for terminating the generation of second messengers induced by chemotactic factor-receptor complexes have, on one hand, suggested a direct role of a GTP-binding protein(s) (G protein), and, on the other hand, proposed that there is a lateral segregation of the ligand receptor complexes into G protein-depleted domains of the plasma membrane. In the present investigation, which addresses these apparently contradictory findings, we found that a substantial part of the alpha subunits of the Gn protein (Gn alpha) in unstimulated neutrophils were associated with a cytoskeletal fraction and that release of these subunits occurred upon stimulation with the chemotactic factor fMet-Leu-Phe. An identical Gn alpha release could also be induced by direct activation of G proteins with guanosine 5'-[gamma-thio]triphosphate or AIF4-. In contrast, the alpha subunits of the stimulatory G protein (Gs alpha) also found associated with the cytoskeletal fraction of unstimulated cells were not released by fMet-Leu-Phe stimulation. However, they were effectively released by direct G-protein activation with guanosine 5'-[gamma-thio]triphosphate. In addition, inhibition of the fMet-Leu-Phe-stimulated modulation of the actin network by pertussis toxin did not affect the fMet-Leu-Phe-induced release of Gn alpha from the cytoskeletal fraction. These observations indicate that fMet-Leu Phe-induced activation of neutrophils involves a specific dissociation of Gn alpha from the cytoskeleton and that this release is not a consequence of the well-known effect of fMet-Leu-Phe on the cytoskeleton of neutrophils. The present data contribute ideas concerning the transducing properties of G proteins in cellular signaling and seem to reconcile the apparently contradictory concepts of how the cytoskeleton participates in the termination of the chemotactic-factor induced generation of second messengers in human neutrophils. PMID- 8341669 TI - Molecular characterization of a short interspersed repetitive element from tobacco that exhibits sequence homology to specific tRNAs. AB - We have characterized a family of tRNA-derived short interspersed repetitive elements (SINEs) in the tobacco genome. Members of this family of SINEs, designated TS, have a composite structure and include a region structurally similar to a rabbit tRNA(Lys), a tRNA-unrelated region, and a TTG repeat of variable length at the 3' end. Southern blot hybridization, together with a search of the GenBank data base, showed that various plants belonging to the families Solanaceae and Convolvulaceae contain sequences homologous to the TS family in the introns and flanking regions of many genes, whereas Arabidopsis in the family Cruciferae and several species of monocoytledonous plants do not. The TS family is widely involved in structural and genetic variations in the genomes of many plants that belong to the order Tubiflorae. All of nine sequences identified in a data base search are truncated at their 5' regions and lack the tRNA-related region of the TS family. We characterized the entire sequence of the members of the TS family and found that this family can be categorized as a member of a group of SINEs with a tRNA(Lys)-like structure, as can several animal SINEs. The TS family can be divided into two major subfamilies by analysis of diagnostic positions, and one of the subfamilies is clearly younger than the other. Amplification of many copies of the full sequence of the younger subfamily occurred during the recent evolution of the tobacco lineage. We also discuss mechanisms that could be involved in the generation of SINEs in animals and also in plants. PMID- 8341670 TI - Local sources of retinoic acid coincide with retinoid-mediated transgene activity during embryonic development. AB - We have assessed whether retinoic acid (RA) comes from local sources or is available widely to activate gene expression in embryos. We used an RA-responsive indicator cell line, L-C2A5, to localize RA sources. In these cells, an RA sensitive promoter/lacZ reporter construct used previously by us to produce indicator transgenic mice is induced globally by RA in medium or locally by RA released at physiological concentrations (1 nM) from AG-1X2 resin beads. Furthermore, the cells are differentially responsive to the 9-cis and all-trans isomers of RA at low concentrations. Indicator transgenic mice with the same promoter/reporter construct were used to identify regions of RA-mediated gene activation. There are distinct domains of lacZ expression in the cervical and lumbar spinal cords of embryonic indicator mice. This pattern might reflect localized RA sources or restricted spatial and temporal expression of RA receptors, binding proteins, or other factors. To resolve this issue we compared the pattern of transgene activation in indicator cell monolayers cocultured with normal embryonic spinal cords with that in transgenic spinal cords. The explants induced reporter gene expression in L-C2A5 monolayers in a pattern identical to that in transgenic mice: alar regions of the cervical and lumbar cord were positive whereas those in the thoracic and sacral regions were not. We conclude that restricted sources of RA in the developing spinal cord mediate the local activation of RA-inducible genes. Thus, region-specific gene activation in embryos can be mediated by precisely localized sources of inductive molecules like RA. PMID- 8341671 TI - A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes. AB - Analysis of mitotic and meiotic recombination in mammalian cells has been hampered by the complexity of the reactions involved as well as lack of mutants. Furthermore, none of the genes involved in the process has yet been identified. In budding yeast, Saccharomyces cerevisiae, the RAD51 gene is essential along with other genes of the RAD52 epistasis group for mitotic and meiotic recombination and DNA repair. The Rad51 protein is structurally similar to Escherichia coli RecA protein, which is required in homologous recombination and SOS responses in bacteria. Here we report the isolation of a mouse homolog of the yeast RAD51 gene. The amino acid sequence predicted from the gene shows 83% and 55% homology with those of the yeast RAD51 and the E. coli recA product, respectively. The mouse gene complemented a rad51 mutation of S. cerevisiae with sensitivity to methyl-methanesulfonate, which produces double-strand breaks of DNA. This gene is expressed in the thymus, testis, ovary, spleen, and intestine, suggesting that its product is involved in mitotic and meiotic recombination in addition to DNA repair. PMID- 8341672 TI - At day 8-8.5 of mouse development the yolk sac, not the embryo proper, has lymphoid precursor potential in vivo and in vitro. AB - We have studied both in vitro and in vivo the formation of lymphocyte progenitors before blood circulation (day 9 of gestation) has started in the mouse embryo, and we have determined the tissue where this occurs. The results demonstrate that the yolk sac of embryos at day 8 and day 8.5 of gestation contains precursor cells that can give rise, in vivo and in vitro, to mature T and B lymphocytes. No lymphoid precursors were found in the embryo proper at this stage of mouse development. The yolk sac cells with lymphocyte precursor potential are most likely multipotent stem cells rather than cell-lineage-determined T- and/or B lymphocyte progenitors. The defined in vitro assays described here that support differentiation of yolk sac stem cells along the T- or B-lymphocyte pathways also may now facilitate the study of the molecular events leading to cell-lineage commitment of lymphocyte progenitors in the mouse embryo. PMID- 8341673 TI - Expression of an atrial G-protein-activated potassium channel in Xenopus oocytes. AB - Injection of rat atrial RNA into Xenopus oocytes resulted in the expression of guanine nucleotide binding (G) protein-activated K+ channel. Current through the channel could be activated by acetylcholine or, if RNA encoding a neuronal 5HT1A receptor was coinjected with atrial RNA, by serotonin (5HT). A 5HT-evoked current (I5HT) was observed in oocytes injected with ventricle RNA fractions (of 2.5-5.5 kb) and 5HT1A receptor RNA. I5HT displayed strong inward rectification with very little conductance above the K+ equilibrium potential, was highly selective for K+ over Na+, and was blocked by 5-300 microM Ba2+. I5HT was suppressed by intracellular injection of the nonhydrolyzable analog of GDP, guanosine 5'-[beta thio]diphosphate, but not by treatment with pertussis toxin (PTX), suggesting coupling of the receptor to the G-protein-activated K+ channel via a PTX insensitive G protein, possibly endogenously present in the oocyte. Coexpression of the alpha subunit of a PTX-sensitive G protein, G(i2), rendered I5HT sensitive to PTX inhibition. Native oocytes displayed a constitutively active inwardly rectifying K+ current with a lower sensitivity to Ba2+ block; expression of a similar current was also directed by atrial or ventricle RNA of 1.5-3 kb. Xenopus oocytes may be employed for cloning of the G-protein-activated K+ channel cDNA and for studying the coupling between this channel and G proteins. PMID- 8341674 TI - Effects of abasic sites and DNA single-strand breaks on prokaryotic RNA polymerases. AB - Abasic sites are thought to be the most frequently occurring cellular DNA damage and are generated spontaneously or as the result of chemical or radiation damage to DNA. In contrast to the wealth of information that exists on the effects of abasic sites on DNA polymerases, very little is known about how these lesions interact with RNA polymerases. An in vitro transcription system was used to determine the effects of abasic sites and single-strand breaks on transcriptional elongation. DNA templates were constructed containing single abasic sites or nicks placed at unique locations downstream from two different promoters and were transcribed by SP6 and Escherichia coli RNA polymerases. SP6 RNA polymerase is initially stalled at abasic sites with subsequent, efficient bypass of these lesions. E. coli RNA polymerase also bypassed abasic sites. In contrast, single strand breaks introduced at abasic sites completely blocked the progression of both RNA polymerases. Sequence analysis of full-length transcripts revealed that SP6 and E. coli RNA polymerases insert primarily, if not exclusively, adenine residues opposite to abasic sites. This finding suggests that abasic sites may be highly mutagenic in vivo at the level of transcription. PMID- 8341675 TI - Transcriptional arrest of yeast RNA polymerase II by Escherichia coli rho protein in vitro. AB - A promoter-independent assay utilizing poly(dC)-tailed DNA templates has revealed that Saccharomyces cerevisiae whole-cell extracts can be proficient for transcription by the endogenous yeast RNA polymerase II as well as for correct 3' end RNA processing. Our attempts to examine the fate of polymerase II itself were inconclusive, because only trace transcription products corresponded to the expected size of terminated RNA species. Transcription in our processing proficient extract was thus insufficient to cause termination. To test our system with a known, albeit heterologous, signal, we examined a dC-tailed template carrying the E. coli rho-dependent termination signal trp t' in the yeast extract. Transcripts from this template were not susceptible to processing, but addition of rho protein resulted in two distinct truncated transcripts that could not be chased by excess unlabeled nucleotides. These RNA species thus represented stably paused or terminated polymerase II products, and their absence when a mutated unresponsive trp t' template was used affirmed that they were due to the effects of rho. E. coli RNA polymerase added to a yeast extract pretreated with alpha-amanitin was also halted by rho at these same two sites. A mutated rho protein, while only partly defective with E. coli polymerase, failed to provoke arrest when transcription was carried out by RNA polymerase II. Thus, functional rho and its cognate site, trp t', appear necessary and sufficient to elicit the production of truncated transcripts by RNA polymerase II in a yeast whole-cell extract. The ability of rho to halt the eukaryotic enzyme strengthens the likelihood that a rho-like helicase may be involved in RNA polymerase II transcription termination. PMID- 8341676 TI - Inhibition of anaphase spindle elongation in vitro by a peptide antibody that recognizes kinesin motor domain. AB - Isolated central spindles or spindles in detergent-permeabilized cells from the diatom Cylindrotheca fusiformis can undergo ATP-dependent reactivation of spindle elongation in vitro. We have used a peptide antibody raised against a 10-amino acid portion common to the kinesin superfamily motor domain to look for kinesin like motor activity during anaphase B of mitosis. The peptide antibody localizes to central spindles. Upon ATP reactivation of spindle elongation, antigens recognized by the antibody are associated exclusively with the central spindle midzone where antiparallel microtubules of each half-spindle overlap. The antibody recognizes several polypeptides by immunoblot using isolated spindle extracts. One of these polypeptides behaves like kinesin with respect to nucleotide-specific binding to and release from taxol-stabilized microtubules. Preincubation of the spindle model with the peptide antibody inhibits subsequent ATP reactivation of spindle elongation. Coincubation of the peptide antibody with peptide antigen rescues spindle function. These results support a role for kinesin-related protein(s) in spindle elongation (anaphase B) of mitosis and suggest that one or several polypeptides that we have identified in spindle extracts may fulfill this function. PMID- 8341677 TI - Heterologous expression of mating-type genes in filamentous fungi. AB - Podospora anserina and Neurospora crassa, two filamentous heterothallic ascomycetes, have a single mating-type locus with two alternate forms called mat+ and mat- and A and a, respectively. Mating type controls entry into the sexual cycle, events subsequent to fertilization, and, in N. crassa, prevents the formation of mixed mating-type heterokaryons. The mating types of these two organisms display similarity in their DNA structure and in the encoded polypeptides involved in fertilization. Here we show that this molecular similarity reflects a functional homology with respect to mating identity. Transformation experiments show that the N. crassa mating-type genes can provide the fertilization functions in P. anserina strains devoid of mating specificity as well as in mat+ and mat- strains. Reciprocally, the introduction of P. anserina mating-type genes confers mating activity in N. crassa. Functional identity between the mating types is not observed for vegetative incompatibility or for post-fertilization events such as meiosis and ascosporogenesis. PMID- 8341678 TI - Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae. AB - The full activity of a recombination initiation site located 5' of HIS4 requires the binding of the transcription factors RAP1, BAS1, and BAS2. Two RAP1 binding sites can substitute for the wild-type initiation site. A 51-bp region of telomeric DNA inserted upstream of either HIS4 or ARG4 very strongly stimulates recombination. We suggest that the ability of transcription factors to induce recombination is a consequence of an altered chromatin structure that favors the entry of proteins that initiate recombination, rather than an effect of these factors on transcription. PMID- 8341679 TI - Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon gamma receptor. AB - Availability of mice with a targeted disruption of the interferon gamma (IFN gamma) receptor gene (IFN-gamma R0/0 mice) made it possible to examine parameters of macrophage activation in the absence of a functional IFN-gamma receptor. We asked to what extent other cytokines could replace IFN-gamma in the induction of nitric oxide or major histocompatibility complex class II antigen (Ia) expression in peritoneal macrophages. In thioglycollate-elicited macrophages from wild-type mice, tumor necrosis factor (TNF) alone was virtually ineffective in inducing release of NO2- (the endproduct of nitric oxide generation), but TNF enhanced NO2 release in the presence of IFN-gamma. In macrophages from IFN-gamma R0/0 mice, which were unresponsive to IFN-gamma, TNF completely failed to stimulate NO2- release. The stimulatory actions of IFN-alpha/beta on NO2- release were indistinguishable in wild-type and IFN-gamma R0/0 macrophages: IFN-alpha/beta was ineffective on its own, showed marginal stimulation of NO2- release in combination with TNF, and was moderately effective in the presence of lipopolysaccharide. The level of constitutive Ia antigen expression was not significantly different in peritoneal macrophages from wild-type and IFN-gamma R0/0 mice. An increased Ia expression was induced by IL-4 and granulocyte macrophage colony-stimulating factor in both wild-type and IFN-gamma R0/0 macrophages, but the magnitude of this induction was less than with optimal concentrations of IFN-gamma in macrophages from wild-type mice. IFN-alpha/beta showed only a minor stimulatory effect on Ia expression in both wild-type and IFN gamma R0/0 macrophages. Simultaneous treatment of wild-type macrophages with IFN alpha/beta and IFN-gamma reduced the IFN-gamma-induced Ia expression in wild-type macrophages, but IFN-alpha/beta did not show an inhibitory effect on IL-4- or granulocyte-macrophage-colony-stimulating factor-induced Ia expression in either wild-type or IFN-gamma R0/0 macrophages. The important role of IFN-gamma in the regulation of the induced expression of major histocompatibility complex class II antigen was confirmed by showing that after systemic infection with the BCG strain of Mycobacterium bovis resident peritoneal macrophages from IFN-gamma R0/0 mice had a lower level of Ia expression than macrophages from wild-type mice. The inability of other cytokines to substitute fully for IFN-gamma in macrophage activation helps to explain the earlier observed decreased resistance of IFN gamma R0/0 mice to some infections. PMID- 8341680 TI - Oxidative tyrosylation of high density lipoprotein by peroxidase enhances cholesterol removal from cultured fibroblasts and macrophage foam cells. AB - Lipoprotein oxidation is thought to play a pivotal role in atherogenesis, yet the underlying reaction mechanisms remain poorly understood. We have explored the possibility that high density lipoprotein (HDL) might be oxidized by peroxidase generated tyrosyl radical. Exposure of HDL to L-tyrosine, H2O2, and horseradish peroxidase crosslinked its apolipoproteins and strikingly increased protein associated fluorescence. The reaction required L-tyrosine but was independent of free metal ions; it was blocked by either catalase or the heme poison aminotriazole. Dityrosine and other tyrosine oxidation products were detected in the apolipoproteins of HDL modified by the peroxidase/L-tyrosine/H2O2 system, implicating tyrosyl radical in the reaction pathway. Further evidence suggests that tyrosylated HDL removes cholesterol from cultured cells more effectively than does HDL. Tyrosylated HDL was more potent than HDL at inhibiting cholesterol esterification by the acyl-CoA:cholesterol acyltransferase reaction, stimulating the incorporation of [14C]acetate into [14C]cholesterol, and depleting cholesteryl ester stores in human skin fibroblasts. Moreover, exposure of mouse macrophage foam cells to tyrosylated HDL markedly diminished cholesteryl ester and free cholesterol mass. We have recently found that myeloperoxidase, a heme protein secreted by activated phagocytes, can also convert L-tyrosine to o,o' dityrosine. This raises the possibility that myeloperoxidase-generated tyrosyl radical may modify HDL, enabling the lipoprotein to protect the artery wall against pathological cholesterol accumulation. PMID- 8341681 TI - Homologous recognition promoted by RecA protein via non-Watson-Crick bonds between identical DNA strands. AB - The RecA protein of Escherichia coli forms a nucleoprotein filament that promotes homologous recognition and subsequent strand exchange between a single strand and duplex DNA via a three-stranded intermediate. Recognition of homology within three-stranded nucleoprotein complexes, which is probably central to genetic recombination, is not well understood as compared with the mutual recognition of complementary single strands by Watson-Crick base pairing. Using oligonucleotides, we examined the determinants of homologous recognition within RecA nucleoprotein filaments. Filaments that contained a single strand of DNA recognized homology not only in a complementary oligonucleotide but also in an identical oligonucleotide, whether their respective sugar-phosphate backbones were antiparallel or parallel, and a filament that contained duplex DNA showed the same polymorphic versatility in the recognition of homology. Recognition of self by a filament that contains a single strand reveals that RecA filaments can recognize homology via non-Watson-Crick hydrogen bonds. Recognition of multiple forms of the same sequence by duplex DNA in the filament shows that it primarily senses base-sequence homology, and suggests that recognition can be accomplished prior to the establishment of new Watson-Crick base pairs in heteroduplex products. However, unlike the initial recognition of homology, strand exchange is stereospecific, requiring the proper antiparallel orientation of complementary strands. PMID- 8341682 TI - Cloning of human erythroid dematin reveals another member of the villin family. AB - Dematin is an actin-bundling protein originally identified in the human erythroid membrane skeleton. Its actin-bundling activity is abolished upon phosphorylation by the cAMP-dependent protein kinase and is restored after dephosphorylation. Here we report the complete primary structure of human erythroid dematin, whose sequence includes a homologue of the "headpiece" sequence found at the C terminus of villin. This headpiece is essential for villin function in inducing microvillar development and actin redistribution. The widespread expression of dematin transcripts in human tissues suggests that dematin and its homologues may substitute for villin in villin-negative tissues to regulate actin reorganization by a phosphorylation-regulated mechanism. PMID- 8341683 TI - VH gene organization in a relict species, the coelacanth Latimeria chalumnae: evolutionary implications. AB - The living coelacanth Latimeria chalumnae is a relict species whose higher-level phylogenetic relationships have not been resolved clearly by traditional systematic approaches. Previous studies show that major differences in immunoglobulin gene structure and organization typify different phylogenetic lineages. To date, mammalian-, avian-, and elasmobranch-type gene organizations have been identified in representatives of these different phylads. A fourth form or organization is found in Latimeria, which possesses immunoglobulin heavy-chain variable region (VH) elements separated by approximately 190 nucleotides from diversity (D) elements. Adjacency of VH and D elements is characteristic of the elasmobranch "clustered" arrangement, although many other features of coelacanth VH gene organization and structure are more similar to those of bony fishes and tetrapods. These observations strongly support a phylogenetic hypothesis in which Latimeria occupies a sister-group relationship with teleosts and tetrapods. PMID- 8341684 TI - Wavelengths effective in induction of malignant melanoma. AB - It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented backcross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. We irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and scored the irradiated animals for melanomas 4 months later. We used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. We interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths > 320 nm--the UV-A and visible spectral regions. PMID- 8341685 TI - A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations. AB - Genetically engineered or chemically purified soluble monovalent major histocompatibility complex (MHC) molecules, which have previously been used to study T cells, have not blocked cytotoxic T-cell responses. Here we describe a genetically engineered divalent class I MHC molecule which inhibits lysis of target cells by alloreactive cytotoxic T cells. This protein, H-2Kb/IgG, was generated as a fusion protein between the extracellular domains of a murine class I polypeptide, H-2Kb, and an immunoglobulin heavy chain polypeptide. The chimeric protein has serological and biochemical characteristics of both the MHC and IgG polypeptides. Nanomolar concentrations of H-2Kb/IgG inhibited lysis of H-2Kb expressing target cells not only by alloreactive H-2Kb-specific T-cell clones but also by alloreactive H-2Kb-specific primary T-cell cultures. A direct binding assay showed high-affinity binding between the H-2Kb/IgG molecule and an H-2Kb specific alloreactive T-cell clone. Unlabeled H-2Kb/IgG displaced 125I-labeled H 2Kb/IgG from T cells with an IC50 of 1.2 nM. PMID- 8341686 TI - Differential organ-specific expression of three poly(A)-binding-protein genes from Arabidopsis thaliana. AB - Poly(A)-binding protein (PABP) is considered an essential component of a eukaryotic cell; deletion of the PABP-coding gene in yeast leads to a lethal phenotype. PABP is implicated in numerous aspects of posttranscriptional regulation, including mRNA turnover and translational initiation. A nested set of degenerate PCR primers designed from regions conserved among yeast, Xenopus, and human PABP sequences was used to amplify genomic DNA fragments from Arabidopsis thaliana. Hybridization screening of genomic and cDNA libraries with a genomic PCR probe led to the isolation of three diverse Arabidopsis genes encoding PABPs, PAB1, PAB3, and PAB5. All three sequences contain the expected four RNA recognition motifs. Sequence diversity between these genes equals or exceeds the diversity among animal and fungal sequences. One of the genes, PAB5, and its cDNA were completely sequenced. Its open reading frame encodes a 73.2-kDa protein containing a number of amino acid motifs characteristic of PABPs from different species. Moreover, in vitro synthesized PAB5 protein bound to poly(A)-Sepharose with high specificity. All three genes isolated showed organ-specific patterns of expression. PAB5 and PAB3 RNAs were detected only in floral organs, with the highest level of expression in immature flowers. PAB1 RNA was observed predominantly in roots, was less abundant in immature flowers, and was not detected in any other organ examined (stems, leaves, mature flowers, siliques). This suggests a potentially unique role for PABPs in organ-specific posttranscriptional regulation in plants. PMID- 8341687 TI - cDNA structure of the mouse and rat subtilisin/kexin-like PC5: a candidate proprotein convertase expressed in endocrine and nonendocrine cells. AB - By using reverse transcriptase/PCR and oligonucleotide sequences derived from conserved segments (including the conserved RRGDL sequence) of the known proprotein convertases (PCs) PC1, PC2, furin, and PC4, we identified a subtilisin/kexin-like PC called PC5 in both mouse and rat tissues. The composite structure (2.85 kb) was deduced from the analysis of the reverse transcription/PCR products combined with the sequence from a clone isolated from a cDNA library made from corticotropin-activated mouse adrenocortical Y1 cells. The deduced cDNA structures of mouse PC5 and rat PC5 showed that the closest homologue is PACE4. Furthermore, like furin, Drosophila melanogaster (d) dfurin2, and PACE4, PC5 shows the presence of a C-terminal Cys-rich domain containing either 5 (PC5 and PACE4) or 10 (dfurin2) repeats of the consensus motif Cys-Xaa2 Cys-Xaa3-Cys-Xaa(5-7)-Cys-Xaa2-Cys-Xaa (8-15)-Cys-Xaa3-Cys-Xaa(9-16). The richest sources of rat PC5 mRNA (3.8 kb) are the adrenal and gut, but it can also be detected in many endocrine and nonendocrine tissues. Corticotropin-stimulated adrenocortical Y1 cells showed an increased expression of PC5 mRNA, suggesting an upregulation by cAMP. In situ hybridization of rat brain sections demonstrated a unique distribution of PC5 compared to PC1, PC2, and furin. PMID- 8341688 TI - Suppression of oncogenic Ras by mutant neurofibromatosis type 1 genes with single amino acid substitutions. AB - NF1 was first identified as the gene responsible for the pathogenesis of the human genetic disorder neurofibromatosis type 1. cDNA cloning revealed that its putative protein product has a domain showing significant sequence homology with the mammalian Ras GTPase activating protein and two yeast Saccharomyces cerevisiae proteins, Ira1 and Ira2. The Ras GTPase activating protein-related domain of the NF1 gene product (NF1-GRD) stimulates GTPase activity of normal Ras proteins but not of oncogenic mutant Ras from both mammalian and yeast cells. Thus, in yeast, NF1-GRD can suppress the heat-shock-sensitive phenotype of ira- cells but not the same phenotype of activated RAS such as RAS2Val19 and RAS2Leu68. We have screened a pool of mutagenized NF1 expression plasmids and obtained two mutant NF1 cDNA clones that can suppress the heat-shock-sensitive phenotype of RAS2Val19 cells. One clone (NF201) suppressed RAS2Leu68, RAS2Ser41, and RAS2Val19, whereas another clone (NF204) preferentially suppressed RAS2Val19. When expressed in mammalian cells, these mutant NF1-GRDs were able to induce the morphological reversion of v-ras-transformed NIH 3T3 cells. Both wild-type and mutant NF1-GRDs can stimulate the GTPase activity of normal but not transforming Ras. We suggest that mutant NF1-GRDs may bind tightly to transforming Ras, which stays in GTP-bound conformation, thus preventing the interaction with the putative effector molecule. On the other hand, normal Ras cannot be sequestered since the bound GTP is rapidly hydrolyzed upon interaction with mutant NF1-GRD to yield Ras-GDP, which is readily released from the NF1-GRD and recycled. PMID- 8341689 TI - Coexpression of neurotrophins and their receptors in neurons of the central nervous system. AB - Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are neuronal survival molecules which utilize the Trk family of tyrosine kinase receptors. Using double-label in situ hybridization, we demonstrate that mRNAs for BDNF and its high-affinity receptor TrkB are coexpressed in hippocampal and cortical neurons. Also, a large number of neurons in these areas coexpress NGF and BDNF mRNAs. Epileptic seizures lead to increased levels of both BDNF/TrkB and NGF/BDNF mRNAs in double-labeled cells. Our results show that individual neurons of the central nervous system can coexpress neurotrophins and their receptors and produce two neurotrophic factors. These factors could support neuronal survival after brain insults, not only via retrograde transport but also through autocrine mechanisms. PMID- 8341690 TI - The serum response element can mediate induction of c-fos by growth hormone. AB - The c-fos protooncogene is transcriptionally activated by a wide variety of agents including serum, growth factors, and phorbol esters. This induction is rapid and transient and is mediated through a number of identified promoter elements. Growth hormone (GH) is also known to induce transcription of c-fos in a variety of cell types including NIH 3T3 fibroblasts and 3T3-F442A preadipocytes. To identify DNA sequences in the c-fos gene regulated by GH, this study sought to determine whether induction of c-fos by GH involves previously identified c-fos promoter elements. A plasmid containing a growth factor-sensitive fragment of the upstream region of the c-fos promoter from -361 to -264 bp was tested for GH sensitivity. The fragment was cloned upstream of a human c-fos reporter [designated FOS by Human Gene Mapping 11 (1991)], which included basal promoter elements. In transiently transfected mouse NIH 3T3 fibroblasts, the promoter fragment conferred GH sensitivity on the human c-fos reporter. To identify a specific GH-sensitive DNA sequence in this promoter, a serum response element (SRE)-reporter plasmid was tested and found to be stimulated by GH. GH was effective in inducing expression through the SRE over a range of physiological GH concentrations. Since GH was recently found to synergize with serum factors in inducing c-fos transcription, the effect of GH and serum on SRE function was examined for insight into the mechanism for such synergism. The combined effect of GH and serum to induce reporter expression through the SRE was greater than the added effects of GH and serum, indicating that the synergism between GH and serum in inducing c-fos involves the SRE sequence. These studies identify the SRE as one specific DNA sequence in the c-fos promoter functionally regulated by GH. It is notable that GH is effective at physiological concentrations. Furthermore, synergism in c-fos induction between GH and serum factors is evident through the SRE. PMID- 8341691 TI - A Jun-binding protein related to a putative tumor suppressor. AB - A lambda gt11 cDNA library of chicken embryo fibroblasts was screened with biotinylated Jun protein to identify Jun-binding clones. Eight such clones were isolated; one contains a gene referred to as jif-1 that is homologous to the putative tumor suppressor gene QM. jif-1 codes for a protein of 25 kDa that binds to the leucine zipper of viral and cellular Jun. The Jif-1 protein also binds to itself. Jif-1 does not contain a leucine zipper, and it does not bind to the 12-O tetradecanoylphorbol 13-acetate response element DNA sequence. Complex formation of Jif-1 with Jun inhibits DNA binding and reduces transactivation by Jun. Addition of Fos protein to Jun-Jif-1 complexes restores DNA-binding activity. These observations suggest that Jif-1 is a negative regulator of Jun. PMID- 8341692 TI - Splice variants of the N-methyl-D-aspartate receptor NR1 identify domains involved in regulation by polyamines and protein kinase C. AB - The N-methyl-D-aspartate (NMDA) receptor NR1 gene encodes RNA that is alternatively spliced to generate at least seven variants. The variants arise from splicing in or out of three exons; one encodes a 21-amino acid insert in the N-terminal domain, and two encode adjacent sequences of 37 and 38 amino acids in the C-terminal domain. Splicing out of the second C-terminal exon deletes a stop codon and results in an additional open reading frame encoding an unrelated sequence of 22 amino acids before arriving at a second stop codon. We denote the NR1 variants by the presence or absence of the three alternatively spliced exons (from 5' to 3'); thus, NR1(111) has all three exons, NR1(000) has none, and NR1(100) has only the N-terminal exon. We report here electrophysiological characterization of six splice variants of the NR1 receptor expressed in Xenopus oocytes. NR1 receptors that lacked the N-terminal exon (NR1(000), NR1(010), and NR1(011)) exhibited a relatively high affinity for NMDA (EC50 approximately 13 microM) and marked potentiation by spermine. In contrast, those receptor variants with the N-terminal insert (NR1(100), NR1(101), and NR1(111)) showed a lower agonist affinity and little or no spermine potentiation at saturating glycine. All six variants showed spermine potentiation at low glycine and inhibition by spermine at more negative potentials. Variants differing only in the C-terminal domain differed little in agonist affinity and spermine potentiation. These findings indicate that the N-terminal insert either participates in agonist and polyamine binding domains or indirectly modifies their conformations. The splice variants differed in the extent to which they could be potentiated by activators of protein kinase C (PKC) from 3- to 20-fold. Presence of the N-terminal insert and absence of the C-terminal sequences increased potentiation by PKC. These findings identify the contributions of the separate polypeptide domains to modulation by polyamines and PKC and provide further support for the concept that subunit composition determines functional properties of NMDA receptors. PMID- 8341693 TI - Hexamethylenebisacetamide-induced erythroleukemia cell differentiation involves modulation of events required for cell cycle progression through G1. AB - Hexamethylenebisacetamide (HMBA), a potent inducer of differentiation of transformed cells such as murine erythroleukemia cells, causes a prolongation of the G1 phase of the cell cycle during which commitment to terminal differentiation is first detected. Removal of HMBA prior to the G1 phase aborts commitment. To further define the relationship between the G1 phase and commitment to differentiation, we used two inhibitors of cell cycle progression: aphidicolin, which blocks cells at the G1/S interphase, and deferoxamine, which blocks cells at an earlier stage during G1. HMBA-induced prolongation of G1 is associated with the accumulation of underphosphorylated retinoblastoma protein, decrease in cyclin A protein levels, and commitment to differentiation. G1 arrest of murine erythroleukemia cells induced by aphidicolin or deferoxamine is not associated with accumulation of under-phosphorylated retinoblastoma protein, suppression of cyclin A protein, or commitment of cells to terminal differentiation. Neither of the cell cycle inhibitors alters the effect of HMBA in inducing the G1-associated changes or commitment to differentiation. Taken together, the present findings indicate that the site of action of HMBA which leads to commitment is in a stage of the G1 phase prior to the point of cell cycle block caused by deferoxamine or aphidicolin. HMBA appears to cause cell differentiation with suppression of cell cycle progression by an action that affects events required for cell progression through G1, including accumulation of underphosphorylated retinoblastoma protein and changes in regulation of cyclin levels. PMID- 8341694 TI - Sequence analysis of the beta-N-acetylhexosaminidase gene of Vibrio vulnificus: evidence for a common evolutionary origin of hexosaminidases. AB - DNA cloned from the marine bacterium Vibrio vulnificus into Escherichia coli HB101 can hydrolyze chitin oligomer analogs in the recipient. The nucleotide sequence of the cloned DNA was determined and a single long open reading frame of 2541 base pairs (initiation codon through termination codon) was found. The nucleotide sequence predicts a gene product of 847 amino acids and a molecular mass of 94.3 kDa. In vitro transcription and translation analyses indicated a single protein of 94 kDa encoded by the cloned DNA. The gene product hydrolyzes methylumbelliferyl beta-D conjugates of chitotriose, chitobiose, N acetylglucosamine, and N-acetylgalactosamine and has, therefore, been termed a beta-N-acetylhexosaminidase. The predicted protein shares a high degree of sequence similarity with the chitobiase of Vibrio harveyi and limited similarity with the alpha chain of human beta-hexosaminidase. Cluster analyses suggest a common evolutionary ancestor for all known hexosaminidase enzymes, with no detectable relationship to known chitinases. PMID- 8341695 TI - Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding. AB - The ability to undergo a particular conformational switch on moving from a polar to a less polar environment has been shown to be conserved at the CD4-binding domain of the envelope glycoprotein gp120 from human immunodeficiency virus type 1 despite considerable variability in primary structure and is essential for the process of binding to the T-cell receptor CD4. The elements necessary to the expression of this behavior have been examined in synthetic peptides using circular dichroism and have been found to include a tetrad, LPCR, plus a tryptophan at a position 8 residues C-terminal to it. In the absence of the tryptophan the conformational change from beta-sheet to alpha-helix as medium polarity decreases does not occur abruptly but, rather, in a linear fashion. In the absence of the LPCR tetrad, no transition to alpha-helix occurs even at 100% trifluoroethanol. These two domains interact to control not only the beta-->alpha transition but also both its cooperativity and the critical point on the polar- >apolar gradient at which it occurs. Sequence similarity searches of the protein data banks suggest that an LPCR tetrad, governing the folding behavior of subsequent residues, may occur as a conserved motif in proteins in general. Synthetic peptides with the sequence of non-gp120 proteins that contain the tetrad do in fact display a similar pattern of folding response to decreasing polarity, with a sharp, cooperative transition from beta-sheet to alpha-helix. The LPCR tetrad appears to be a motif that controls secondary structure in a manner supplementary to that predicted by folding algorithms. PMID- 8341696 TI - Dimerization and DNA binding alter phosphorylation of Fos and Jun. AB - Fos and Jun form dimeric complexes that bind to activator protein 1 (AP-1) DNA sequences and regulate gene expression. The levels of expression and activities of these proteins are regulated by a variety of extracellular stimuli. They are thought to function in nuclear signal transduction processes in many different cell types. The role of Fos and Jun in gene transcription is complex and may be regulated in several ways including association with different dimerization partners, interactions with other transcriptional factors, effects on DNA topology, and reduction/oxidation of a conserved cysteine residue in the DNA binding domain. In addition, phosphorylation has been suggested to control the activity of Fos and Jun. Here we show that phosphorylation of Fos and Jun by several protein kinases is affected by dimerization and binding to DNA. Jun homodimers are phosphorylated efficiently by casein kinase II, whereas Fos-Jun heterodimers are not. DNA binding also reduces phosphorylation of Jun by casein kinase II, p34cdc2 (cdc2) kinase, and protein kinase C. Phosphorylation of Fos by cAMP-dependent protein kinase and cdc2 is relatively insensitive to dimerization and DNA binding, whereas phosphorylation of Fos and Jun by DNA-dependent protein kinase is dramatically stimulated by binding to the AP-1 site. These results imply that different protein kinases can distinguish among Fos and Jun proteins in the form of monomers, homodimers, and heterodimers and between DNA-bound and non-DNA-bound proteins. Thus, potentially, these different states of Fos and Jun can be recognized and regulated independently by phosphorylation. PMID- 8341697 TI - The Saccharomyces cerevisiae PRP21 gene product is an integral component of the prespliceosome. AB - In Saccharomyces cerevisiae, the prp21 mutation causes accumulation of unspliced pre-mRNA at the nonpermissive temperature. We have cloned the PRP21 gene by complementation of its temperature-sensitive phenotype and found it to be the same as SPP91, an extragenic suppressor of the prp9 mutation previously studied in vivo by Chapon and Legrain [Chapon, C. & Legrain, P. (1992) EMBO J. 11, 3279 3288]. We have analyzed the effects of the prp21 mutation on splicing in vitro and have found that PRP21 is a splicing factor required for prespliceosome assembly. We also have analyzed the interaction of PRP21 with splicing complexes using anti-PRP21 antibodies and found that the RNA components of the prespliceosome--U1 and U2 small nuclear RNA (snRNA) particles and pre-mRNA--are specifically coimmunoprecipitated under splicing conditions in the presence of 0.2 M KCl. At higher KCl concentrations, U1 snRNP dissociates from splicing complexes; nevertheless, U2 snRNA and pre-mRNA are still efficiently immunoprecipitated. Immunoprecipitation of both U1 and U2 snRNA as well as pre mRNA is ATP-dependent and requires a pre-mRNA capable of supporting prespliceosome assembly. Analysis of the unbound complexes in native gels confirmed that prespliceosomes are specifically immunoprecipitated by anti-PRP21 antibodies. These results demonstrate that PRP21 is an integral component of the prespliceosome and establishes a stable interaction with U2 snRNP and/or pre-mRNA in that complex. PMID- 8341698 TI - An unusual RNA tertiary interaction has a role for the specific aminoacylation of a transfer RNA. AB - The nucleotides in a tRNA that specifically interact with the cognate aminoacyl tRNA synthetase have been found largely located in the helical stems, the anticodon, or the discriminator base, where they vary from one tRNA to another. The conserved and semiconserved nucleotides that are responsible for the tRNA tertiary structure have been shown to have little role in synthetase recognition. Here we report that aminoacylation of Escherichia coli tRNA(Cys) depends on the anticodon, the discriminator base, and a tertiary interaction between the semiconserved nucleotides at positions 15 and 48. While all other tRNAs contain a purine at position 15 and a complementary pyrimidine at position 48 that establish the tertiary interaction known as the Levitt pair, E. coli tRNA(Cys) has guanosine -15 and -48. Replacement of guanosine -15 or -48 with cytidine virtually eliminates aminoacylation. Structural analyses with chemical probes suggest that guanosine -15 and -48 interact through hydrogen bonds between the exocyclic N-2 and ring N-3 to stabilize the joining of the two long helical stems of the tRNA. This tertiary interaction is different from the traditional base pairing scheme in the Levitt pair, where hydrogen bonds would form between N-1 and O-6. Our results provide evidence for a role of RNA tertiary structure in synthetase recognition. PMID- 8341699 TI - Rare scleroderma autoantibodies to the U11 small nuclear ribonucleoprotein and to the trimethylguanosine cap of U small nuclear RNAs. AB - We have identified a scleroderma serum (Ru) with a previously undescribed specificity to protein components of the U11 small nuclear ribonucleoprotein particle (snRNP), a low-abundance member of the Sm class of U RNPs. The U11 RNP can be specifically immunoprecipitated from sonicated HeLa cells with Ru serum. In nuclear extracts, a fraction of the U11 particle is found complexed to the U12 RNP, an even lower abundance Sm snRNP. In glycerol gradient fractions, Ru serum identifies a 65-kDa protein that cosediments with the U11-U12 complex and is shifted upon targeted degradation of the U12 RNA. The 65-kDa protein therefore appears to be a component of the U11-U12 snRNP complex, whereas another Ru reactive (140 kDa) protein may be associated with the free U11 RNP. The Ru serum also contains autoantibodies directed against the trimethylguanosine cap of U RNAs. This rare specificity has been described previously in only three other scleroderma patients. PMID- 8341700 TI - On how a myosin tryptophan may be perturbed. AB - A well-known indication that a nucleotide has bound to myosin is the enhancement of the fluorescence of a specific tryptophan in the "subfragment 1" segment of the protein. Empirically the effect has been enormously useful in myosin enzymology. But beyond an early suggestion that it arises from a purine tryptophan charge-transfer complex, the mechanism of the effect has not been considered. Here we consider the alternative that it arises from an ionizable group (either another residue or the phosphate of the nucleotide) whose proximity to the tryptophan is altered by substrate binding. We study this possibility by studying the interaction of an ionizable residue and tryptophan when both are incorporated in a diketopiperazine structure. The geometry of the situation is inferred from molecular mechanics simulations. Unexpectedly, the best explanation seems to be that the field of the imposed charge, acting across space, affects events in the excited state of the indole. PMID- 8341701 TI - Construction of a yeast artificial chromosome contig spanning the spinal muscular atrophy disease gene region. AB - The childhood spinal muscular atrophies (SMAs) are the most common, serious neuromuscular disorders of childhood second to Duchenne muscular dystrophy. A single locus for these disorders has been mapped by recombination events to a region of 0.7 centimorgan (range, 0.1-2.1 centimorgans) between loci D5S435 and MAP1B on chromosome 5q11.2-13.3. By using PCR amplification to screen yeast artificial chromosome (YAC) DNA pools and the PCR-vectorette method to amplify YAC ends, a YAC contig was constructed across the disease gene region. Nine walk steps identified 32 YACs, including a minimum of seven overlapping YAC clones (average size, 460 kb) that span the SMA region. The contig is characterized by a collection of 30 YAC-end sequence tag sites together with seven genetic markers. The entire YAC contig spans a minimum of 3.2 Mb; the SMA locus is confined to roughly half of this region. Microsatellite markers generated along the YAC contig segregate with the SMA locus in all families where the flanking markers (D5S435 and MAP1B) recombine. Construction of a YAC contig across the disease gene region is an essential step in isolation of the SMA-encoding gene. PMID- 8341702 TI - Conserved structure of amphibian T-cell antigen receptor beta chain. AB - All jawed vertebrates possess well-differentiated thymuses and elicit T-cell-like cell-mediated responses; however, no surface T-cell receptor (TCR) molecules or TCR genes have been identified in ectothermic vertebrate species. Here we describe cDNA clones from an amphibian species, Ambystoma mexicanum (the Mexican axolotl), that have sequences highly homologous to the avian and mammalian TCR beta chains. The cloned amphibian beta chain variable region (V beta) shares most of the structural characteristics with the more evolved vertebrate V beta and presents approximately 56% amino acid identities with the murine V beta 14 and human V beta 18 families. The two different cloned axolotl beta chain joining regions (J beta) were found to have conserved all the invariant mammalian J beta residues, and in addition, the presence of a conserved glycine at the V beta-J beta junction suggests the existence of diversity elements. The extracellular domains of the two axolotl beta chain constant region isotypes C beta 1 and C beta 2 show an impressively high degree of identity, thus suggesting that a very efficient mechanism of gene correction has been in operation to preserve this structure at least from the early tetrapod evolution. The transmembrane axolotl C beta domains have been less well conserved when compared to the mammalian C beta but they do maintain the lysine residue that is thought to be involved in the charged interaction between the TCR alpha beta heterodimer and the CD3 complex. PMID- 8341703 TI - Cloning and characterization of cyclophilin C-associated protein: a candidate natural cellular ligand for cyclophilin C. AB - We report the protein purification and the cloning and characterization of a cDNA encoding the proteins that bind with high affinity to cyclophilin C (Cyp-C) in the absence of cyclosporin A. Transfection of this cDNA into COS cells directs the production of a glycoprotein of 77 kDa that binds to Cyp-C in the absence, but not the presence, of cyclosporin A. Homology comparisons reveal that this protein and gene, termed CyCAP for Cyp-C-associated protein, possess a cysteine rich domain (scavenger receptor cysteine-rich domain) found in a variety of cell surface molecules; the rest of the sequence is apparently specific. This result raises the possibility that Cyp-C serves as a mediator or regulator of an as-yet unidentified signal or cellular process initiated via the Cyp-C-associated protein. PMID- 8341704 TI - Even in culture, oligodendrocytes myelinate solely axons. AB - Cerebral hemispheres from mouse embryos at 15 days of gestation were dissociated and maintained in culture for several weeks in a medium which permitted homochronic and homotypic oligodendrocytes and neurons to interact in the presence of other central nervous system cells. After 13-14 days in culture a few oligodendrocytes changed from highly branched, "sun-like," nonmyelinating cells to sparcely branched myelinating cells. The number of fibers myelinated per oligodendrocyte ranged from 1 to 10, similar to that described previously in vivo in the corpus callosum. When an oligodendrocyte began to myelinate, it immediately myelinated a maximum number of fibers, suggesting that the number of axons to be myelinated by the oligodendrocyte was predetermined. When only one fiber was in the vicinity of a myelinating oligodendrocyte, whorls of myelin-like figures were seen at the tip of oligodendrocyte processes that had not reached an axon. Myelinated fibers were unambiguously identified as axons both by immunostaining and by electron microscopy. Myelin was not observed around astrocyte processes or around dendrites. The exclusive myelination of axons suggests the existence of a specific axonal recognition signal which attracts oligodendrocyte processes. PMID- 8341705 TI - A tobacco gene family for flower cell wall proteins with a proline-rich domain and a cysteine-rich domain. AB - Flowering is known to be associated with the induction of many cell wall proteins. We report here five members of a tobacco gene family (CELP, Cys-rich extensin-like protein) whose mRNAs are found predominantly in flowers and encode extensin-like Pro-rich proteins. CELP mRNAs accumulate most abundantly in vascular and epidermal tissues of floral organs. In the pistil, CELP mRNAs also accumulate in a thin layer of cells between the transmitting tissue and the cortex of the style and in a surface layer of cells of the placenta in the ovary. This unique accumulation pattern of CELP mRNAs in the pistil suggests a possible role in pollination and fertilization processes. CELP genes encode a class of plant extracellular matrix proteins that have several distinct structural features: a Pro-rich extensin-like domain with Xaa-Pro3-7 motifs and Xaa-Pro doublets, a Cys-rich region, and a highly charged C terminus. The extensin-like domains in these proteins differ significantly in their length and these differences appear to be results of both long and short deletions within the coding regions of their genes. Furthermore, the number of charged amino acid residues in the C-terminal region varies among the CELPs. These structural differences may contribute to functional versatility in the CELPs. On the other hand, the Cys-rich domain is highly conserved among CELPs and the positions of the Cys residues are conserved, suggesting that this region may have a common functional role. The presence of a Pro-rich domain and a Cys-rich domain in these CELPs is reminiscent of a class of hydroxyproline-rich glycoproteins, solanaceous lectins, that are believed to be important in cell-cell recognition. The structure of these CELPs indicates that they may be multifunctional and that their genes may have arisen from recombinational events. PMID- 8341706 TI - Overexpression, characterization, and purification of a recombinant mouse immunophilin FKBP-52 and identification of an associated phosphoprotein. AB - To gain insight into the structure and function of the immunophilin FKBP-52, a mouse FKBP-52 was overexpressed in Spodoptera frugiperda insect cells (Sf9 cells) with the baculovirus expression system. The purification and characterization of the recombinant FKBP-52 (rFKBP-52) was facilitated by incorporating a histidine 6 mer domain at its N terminus. The rFKBP-52 was highly purified on a N(i)2+ affinity resin with an estimated recovery of 10 mg of pure protein from 1 liter of Sf9 cell culture. Subcellular fractionation revealed that the rFKBP-52 is expressed predominantly in the nuclei of infected Sf9 cells maximally at 48 hr after infection, consistent with the nuclear localization of FKBP-52 in mammalian cells. The rFKBP-52 can be assembled in vitro with the glucocorticoid receptor complex, establishing its functionality and confirming that it is a component of the unactivated glucocorticoid receptor complex. The rFKBP-52 possesses an ATP/GTP binding activity that is stimulated by divalent cations. Furthermore, incubation of purified rFKBP-52 with [gamma-32P]ATP and MgCl2 resulted in the phosphorylation of a 59-kDa nuclear protein. Amino acid sequence analysis of this protein revealed that it is a phosphoprotein or kinase that is associated with the rFKBP-52. PMID- 8341707 TI - cdc2-like kinase from rat spinal cord specifically phosphorylates KSPXK motifs in neurofilament proteins: isolation and characterization. AB - A protein kinase that phosphorylates a specific KSP sequence [K(S/T)PXK], which is abundant in high molecular weight neurofilament (NF) proteins, was identified and isolated from rat spinal cord. Characterization of this enzyme activity revealed a close relationship with p34cdc2 kinase with respect to its molecular mass (32.5 kDa by SDS/PAGE) and substrate specificities. It could phosphorylate a synthetic peptide analog of the simian virus 40 large tumor antigen, reportedly a specific substrate for p34cdc2 kinase. Histone (H1) and peptide analogs of the KSP sequence present in the C-terminal end of rat and mouse neurofilament proteins were phosphorylated. This kinase did not phosphorylate alpha-casein and peptide substrates of other known second messenger-dependent or -independent kinases. Dephosphorylated rat NF protein NF-H was strongly phosphorylated by the purified enzyme; NF proteins NF-M and native NF-H, but not NF-L, were slightly phosphorylated. Studies on synthetic peptide analogs of KSP repeats with substitution of specific residues, known to be present in the C-terminal regions of NF-H, revealed a consensus sequence of X(S/T)PXK, characteristic of the p34cdc2 kinase substrate. On Western blots, the enzyme was immunoreactive with antibody against the C-terminal end of cdc2 kinase (mouse) and neuronal cdc2-like kinase from rat but not with an antibody against the conserved PSTAIRE region of the p34cdc2 kinase. The antibody against the C-terminal end of cdc2 kinase could immunoprecipitate (immunodeplete) the purified kinase activity. Since the adult nervous system is composed primarily of postmitotic cells, the present observations indicate a nonmitotic role for this cdc2-like kinase activity. The effective phosphorylation of NF-H by this kinase suggests a function in axonal structure. PMID- 8341708 TI - The functional form of the erythropoietin receptor is a 78-kDa protein: correlation with cell surface expression, endocytosis, and phosphorylation. AB - An abundant 70- to 78-kDa form of the erythropoietin receptor (EPOR) was observed in HC-D57 murine erythroleukemia cells deprived of erythropoietin (EPO). In contrast to the 64- and 66-kDa EPOR proteins, these high molecular mass forms of EPOR (hmm-EPOR) correlated well with the number of binding sites and endocytosis of EPO. The hypothesis that hmm-EPOR are more highly glycosylated forms of the EPOR, appear on the cell surface, and represent at least one component of the biologically active EPOR was tested. Consistent findings were as follows. (i) Only hmm-EPOR increased following withdrawal of EPO from HC-D57 cells, correlating with a 10-fold increase in binding of 125I-labeled EPO. In addition, the EPO-dependent downregulation of 125I-EPO binding and disappearance of hmm EPOR occurred in parallel while the amount of 66-kDa EPOR did not change. (ii) The 78-kDa EPOR was detected in COS cells expressing EPOR cDNA. (iii) Probing of the intact surface of these cells with anti-NH2-terminal antibody recovered only the 78-kDa EPOR. (iv) Enzymatic deglycosylation and dephosphorylation showed that hmm-EPOR apparently resulted from additional N-linked glycosylation of a 62-kDa EPOR. (v) The hmm-EPOR turnover in HC-D57 cells was accelerated 12-fold in the presence of EPO (half-life changed from 3 hr to 15 min). (vi) Anti phosphotyrosine antiserum detected an EPO-dependent phosphorylation of the 78-kDa EPOR. The kinetics of tyrosine phosphorylation of a 97-kDa protein correlated with the occupancy and internalization of hmm-EPOR. In summary, we suggest that the 78-kDa EPOR is directly involved in the initial biological actions of EPO. PMID- 8341709 TI - Sea urchin early histone H2A modulator binding factor 1 is a positive transcription factor also for the early histone H3 gene. AB - To shed some light on the mechanisms involved in the coordinate regulation of the early histone gene set during sea urchin development, we tested the hypothesis that the upstream sequence element USE1, previously identified in the early H2A modulator, could also participate in the transcription of the early histone H3 gene. We found by DNAse I protection analysis and by competition in electrophoretic mobility-shift experiments that two sequence elements of the H3 promoter closely resembled the USE1-H2A sequence in their binding activity for nuclear factors from 64-cell stage embryos. These modulator binding factor 1 (MBF 1)-related factors seem to recognize the ACAGA motif that is conserved between the USE1-like sequences of both H2A and H3 promoters. In fact, excess oligonucleotide containing a mutated USE1-H2A element in which the ACAGA sequence was mutated to AGTCA failed to compete with the USE1 sites of both H2A and H3 genes for interaction with MBF-1. Finally, in vivo transcriptional analysis in both Xenopus and sea urchin showed that an excess of USE1-H2A element efficiently competed for the activity of the H3 promoter. From these results we conclude that MBF-1 is a transcription factor conserved between sea urchin and frog and that MBF-1 or related transcription factors are involved in the coordinate expression of both H2A and H3 early histone genes. PMID- 8341710 TI - PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. AB - cDNAs representing the alpha subunit of polyomavirus enhancer binding protein 2 (PEBP2; also called PEA2) were isolated. The products of the cDNAs are highly homologous to that of Drosophila segmentation gene runt (run) for an N-proximal 128-amino acid region showing 66% identity. The run homology region encompasses the domain capable of binding to a specific nucleotide sequence motif and of dimerizing with the companion beta subunit. The human AML1 gene related to t(8;21) acute myeloid leukemia also had a run homology region. Together with the beta subunit, which increases the affinity of the alpha subunit to DNA without binding to DNA by itself, PEBP2 represents a newly discovered family of transcription factor. The major species of PEBP2 alpha mRNA was expressed in T cell lines but not in B-cell lines tested. Evidence indicated that PEBP2 functions as a transcriptional activator and is involved in regulation of T-cell specific gene expression. PMID- 8341712 TI - The linker of des-Glu84-calmodulin is bent. AB - The crystal structure of a mutant calmodulin (CaM) lacking Glu-84 has been refined to R = 0.23 using data measured to 2.9-A resolution. In native CaM the central helix is fully extended, and the molecule is dumbbell shaped. In contrast, the deletion of Glu-84 causes a bend of 95 degrees in the linker region of the central helix at Ile-85. However, EF-hand domains 1 and 2 (lobe 1,2) do not touch lobe 3,4. The length, by alpha-carbon separation, of des-Glu84-CaM is 56 A; that of native CaM is 64 A. The shape of des-Glu84-CaM is similar to that of native CaM, as it is bound to the target peptide of myosin light-chain kinase. This result supports the proposal that the linker region of the central helix of CaM functions as a flexible tether. PMID- 8341711 TI - Intervening sequence with conserved open reading frame in eubacterial 23S rRNA genes. AB - An intervening sequence (IVS) occurred in the 23S rRNA genes (rrl) of some, but not all, strains of four species of the spirochete genus Leptospira and was absent from strains in three other species. The IVS varied in size from 485 to 759 base pairs and replaced bases 1224-1245 in both copies of rrl. The two ends of each IVS shared 22-35 bases of complementarity that could form a stable double helix. The presence of an IVS correlated with a cleaved mature 23S rRNA that probably results from removal of the IVS without religation. The 3' site of cleavage was mapped within the inverted repeat of the IVS. An open reading frame of 121-133 amino acids was conserved in the IVS in all four species, oriented so that the sense strand was in the rRNA transcript. When the open reading frames were compared between species, they predicted polypeptides that showed between 51% and 78% amino acid conservation and similar DNA sequence conservation, indicating selection for protein function. PMID- 8341713 TI - Genomic mapping with I-Ceu I, an intron-encoded endonuclease specific for genes for ribosomal RNA, in Salmonella spp., Escherichia coli, and other bacteria. AB - Construction of physical maps of genomes by pulsed-field gel electrophoresis requires enzymes which cut the genome into an analyzable number of fragments; most produce too many fragments. The enzyme I-Ceu I, encoded by a mobile intron in the chloroplast 23S ribosomal RNA (rrl) gene of Chlamydomonas eugametos, cuts a 26-bp site in the rrl gene. This enzyme digests DNA of Salmonella typhimurium at seven sites, each corresponding to one of the rrl genes of the rrn operons, but at no other site. These seven fragments were located on the previously determined Xba I physical map, and the I-Ceu I sites, and thus the rrn genes of S. typhimurium, were mapped on the 4800-kb chromosome. Escherichia coli K-12 also yields seven fragments of sizes similar to those of S. typhimurium, indicating conservation of rrn genes and their location, and a chromosome size of 4600 kb. The sizes of the E. coli fragments are close to the size predicted from restriction maps and nucleotide sequence. The I-Ceu I maps of Salmonella enteritidis, Salmonella paratyphi A, B, C, and Salmonella typhi were deduced after digesting genomic DNA and I-Ceu I and probing with DNA of S. typhimurium; the data indicated strong conservation of rrn gene number and position and genome sizes up to 4950 kb. Digestion of DNA of other bacteria (species of Haemophilus, Neisseria, Proteus, and Pasteurella) suggested that only rrn genes are cut in all these species. I-Ceu I digestion followed by pulsed-field gel electrophoresis is a powerful tool for determining genome structure and evolution. PMID- 8341714 TI - Unusual microtubule-dependent endocytosis mechanisms triggered by Campylobacter jejuni and Citrobacter freundii. AB - Bacterial invasion of six different human epithelial cell lines showed that some strains of the intestinal pathogen Campylobacter jejuni invaded intestinal cell lines at a level 10(2)-10(4) times higher than reported previously for other Campylobacter strains. Separately, urinary tract isolates of Citrobacter freundii triggered a high-efficiency invasion of bladder cells. Use of multiple inhibitors with known effects on eukaryotic cell structures/processes allowed us to define in these genetically distinct bacterial genera unusual bacterial invasion mechanisms that uniquely require microtubules but not microfilaments. Campylobacter jejuni strain 81-176 uptake into 407 intestinal cells and Citrobacter entry into T24 bladder cells was blocked by microtubule depolymerization and inhibitors of coated-pit formation but not by microfilament depolymerization. Inhibitors of endosome acidification had no significant impact on intracellular survival of Campylobacter jejuni or Citrobacter freundii, but monensin markedly reduced Citrobacter uptake. Epithelial cell invasion by both of these bacterial genera was dependent upon de novo bacterial protein synthesis but not upon de novo eukaryotic cell protein synthesis. In contrast to the T24 cell line-specific, strict microtubule-dependent uptake, Citrobacter entry into other cell lines was inhibited by both microtubule- and microfilament-depolymerization, suggesting that these bacteria encode two separate pathways for uptake (i, microtubule-dependent; ii, microfilament-dependent) that are cell line-specific and are recognized perhaps depending on the presence and abundance of appropriate eukaryotic receptors. PMID- 8341716 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 8341715 TI - Diazepam dependence prevented by glutamate antagonists. AB - Long-term treatment leads to tolerance to and dependence on benzodiazepines. Abrupt termination of benzodiazepine administration triggers the expression of signs of dependence. Mice withdrawn from chronic treatment with diazepam showed a time-related evolution of anxiety, muscle rigidity, and seizures between days 4 and 21 after treatment discontinuation. A period between withdrawal days 1 and 3 was symptom-free. Surprisingly, during this "silent phase" the susceptibility of mice to alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate (ATPA) and kainate seizures and the magnitude of monosynaptic reflexes mediated by non-N methyl-D-aspartate (NMDA) mechanisms were enhanced. In apparent contrast, the "active phase", between withdrawal days 4 and 21, was characterized by increased susceptibility to NMDA seizures and enhanced magnitude of polysynaptic reflexes, which are NMDA dependent. Treatment of mice with alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionate (AMPA) antagonists 1-(4-aminophenyl)-4-methyl-7,8 methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) or 2,3-dihydroxy-6-nitro-7 sulfamoylbenzo(f)quinoxaline but not with the NMDA antagonist 3-[(+/-)-2 carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) during the silent phase prevented signs of dependence. In contrast, treatment with CPP but not with GYKI 52466 during the active phase prevented the symptoms. The development of tolerance to and dependence on diazepam was prevented by concurrent treatment of mice with CPP but was not prevented by GYKI 52466. These data indicate that NMDA dependent mechanisms contribute to the development of tolerance to diazepam and to the expression of signs of dependence in mice after termination of long-term treatment with diazepam. Nevertheless, the non-NMDA-mediated silent phase is essential for triggering the symptoms. Therefore, AMPA antagonists may offer a therapeutic approach for preventing dependence on benzodiazepines that is an alternative to NMDA antagonism. PMID- 8341717 TI - Role of eicosanoids in the pathogenesis of atopic dermatitis. PMID- 8341719 TI - The effect of 16,16-dimethyl prostaglandin E2 on proliferation of an intestinal goblet cell line and its synthesis and secretion of mucin glycoproteins. AB - The effect of 16,16'-dimethyl prostaglandin E2 (dmPGE2) on the human colonic adenocarcinoma derived mucus-secreting goblet cell line HT29-18N2 was investigated. The proliferation rate of HT29-18N2 was increased by exposure to 10 or 100 microM dmPGE2. Exposure to 10 or 100 microM dmPGE2 caused a significant decrease in the rate of radiolabeled glucosamine incorporation into newly synthesized glycoproteins during an 8 or 24 h exposure. At concentrations as low as 1 microM, dmPGE2 accelerated the secretion of mucin glycoproteins as assessed by the release of newly synthesized radiolabeled glycoproteins, a mucin-specific enzyme-linked immunoassay and a whole-mount immunofluorescence assay. A 1 h exposure to dmPGE2 did not, however, result in a morphometrically detectable decrease in intracellular mucous granule stores or elicit any other readily detectable morphological change. The experimental results suggest elevated levels of PGs may contribute to the previously recognized decreases in intracellular mucin stores and shifts in the types of mucins species present at sites of mucosal inflammation in ulcerative colitis patients. PMID- 8341718 TI - The effects of prostacyclin analog OP-41483 on normothermic liver ischemia and reperfusion injury in rats. AB - To estimate the effects of the prostacyclin analog (OP-41483) on normothermic liver ischemia and reperfusion injury, saline (Group 1, N = 8), heparin (group 2, N = 8, 100 u/kg) or OP-41483 (group 3, N = 8, 400 ng/kg/min) was infused intravenously for 30 min before and after liver ischemia in rats. There were no significant differences in survival, or transaminase at 30 min after reperfusion among the three groups. Hepatic vessel flow and tissue flow were measured for the first 30 min after reperfusion. Hepatic tissue flow increased for the first 30 min after reperfusion in the group 3 rats, but not in the groups 2 and 3 rats. There were significant differences in hepatic tissue flow between the groups 1 and 3 rats at 20 min (p < 0.05), as well as significant differences between the groups 1 and 3 rats (p < 0.01) and the groups 1 and 2 rats (p < 0.05) at 30 min after reperfusion. There were no significant differences in total hepatic inflow among the three groups. Our data suggest that OP-41483 exerts beneficial effects by improving the microcirculation and increasing the effective hepatic blood flow in the ischemically injured liver after reperfusion. PMID- 8341720 TI - Isolation, identification and synthesis of an endogenous arachidonic amide that inhibits calcium channel antagonist 1,4-dihydropyridine binding. AB - This study was part of a broad search for endogenous regulators of L-type calcium channels. The screening for active fractions was done by measuring inhibition [3H]1,4-dihydropyridine (DHP) binding to rat cardiac and cortex membranes. An inhibitory fraction, termed lyophilized brain hexane-extractable inhibitor (LBHI), was isolated from hexane extracts of lyophilized calf brain. The active substance was purified by a series of chromatographic steps. 13C nuclear magnetic resonance (NMR), 1H coherence spectroscopy (COSY) NMR and fast atom bombardment (FAB) mass spectroscopy suggested that LBHI was N-arachidonic acid-2 hydroxyethylamide. Synthesis of this substance and subsequent high performance liquid chromatography (HPLC) and NMR analysis confirmed this structure. Synthetic LBHI (SLBHI) inhibited [3H]DHP binding to rat cortex membranes with an IC50 value of congruent to 15 microM and a Hill coefficient of congruent to 2. Saturation analysis in the presence of SLBHI showed a change in KD (equilibrium dissociation constant), but not maximal binding capacity (Bmax). SLBHI produced an increased dissociation rate, which, along with the Hill slope of > 1, suggested a non competitive interaction with the DHP binding site. The results suggest that arachidonic acid derivatives may be endogenous modifiers of the DHP calcium antagonist binding site. PMID- 8341721 TI - Characterization of (5Z)-7-[3-endo-[(4-iodophenylsulfonyl) amino] bicyclo[2.2.1]hep-2-exo-yl]heptenoic acid (IS-145) as an antagonist for the study of thromboxane A2 receptor. AB - (5Z)-7-[3-endo-[(4-iodophenylsulfonyl) amino]bicyclo[2.2.1]-hep-2-exo-yl] heptenoic acid (IS-145) was characterized on its suitability for the study of thromboxane A2 (TXA2) receptor. Both the I-125 and I-127 analogs are very potent TXA2 antagonist. The I-127 analog interacted with the receptor specifically as shown by the displacement of [3H]-SQ29548 from its binding sites on human platelet membranes in a dose dependent manner. It also elicited specific biological responses by inhibiting I-BOP induced platelet aggregation. However, they failed to inhibit those induced by platelet activating factor. Moreover, it interfered with the TXA2 receptor activated signal transduction system by inhibiting I-BOP induced increase in GTP-gamma-[35S] binding and GTPase activity. These data indicated that IS-145 was indeed a specific antagonist. The I-125 analog was used as a radioactive ligand to characterize TXA2 receptor in human platelet membranes. The binding was found to be saturable, reversible and specific with a KD of 5.8 nM and a Bmax of 1.9 pmol/mg protein. PMID- 8341722 TI - Pharmacological model for airway hypersensitivity produced by propranolol and reserpine in guinea pigs. AB - Combined treatment with propranolol and reserpine enhanced acetylcholine-induced dose-response curves for bronchoconstriction in guinea pigs in vivo. This airway hyperreactivity model was investigated pharmacologically. (1) Increased capillary permeability and increases in leukocytes in bronchoalveolar lavage fluid (BALF) were not observed after this combined treatment. (2) The increased airway sensitivity to acetylcholine produced by propranolol and reserpine was inhibited by ketotifen and theophylline, reported in clinical studies to inhibit airway hyperreactivity. (3) Two leukotriene (LT) receptor antagonists, MCI-826 and FPL 55712, clearly inhibited this increased airway reactivity. (4) A thromboxane A2 (TXA2) receptor antagonist, ONO-3708, and TXA2 synthetase inhibitor, OKY-046, also inhibited this increased airway reactivity. These results suggest that the airway hyperreactivity model produced by propranolol and reserpine in guinea pigs is a valuable pharmacological tool for investigating a remedy and LT and TXA2 may be involved in the onset of this airway hyperreactivity. PMID- 8341723 TI - Hyperoxia decreases cyclooxygenase activity in endothelial cells. AB - We examined the effect of hyperoxia on arachidonic acid (AA) metabolism in bovine carotid artery endothelial cells (CAEC) and pulmonary artery endothelial cells (PAEC). Confluent monolayers were exposed to hyperoxic gases (95% O2 or 60% O2) from 12-72 h. Control cells were incubated under normoxic condition (air-5% CO2). After exposure of the cells to normoxic or hyperoxic conditions, prostaglandin (PG) synthesis activity was analyzed in cell homogenates using thin layer chromatography; release of 6-keto-PGF1 alpha, a stable metabolite of PGI2, into the culture medium was measured using a radioimmunoassay. The major metabolites formed from exogenously supplied 14C-AA were 6-keto-PGF1 alpha and a small amount of PGE2. Hyperoxia (95% O2) decreased the synthesis of these cyclooxygenase products beginning at 24 h; moderate hyperoxia (60% O2) had no such effect. There was no significant difference between CAEC and PAEC with respect to the depletion effect of hyperoxia. After 72 h of exposure to 95% O2, endothelial injury was observed in CAEC but not in PAEC. We conclude that hyperoxia decreases cyclooxygenase activity in endothelial cells, and that this decrease is dependent on the severity of the hyperoxia. In addition, CAEC are more susceptible to hyperoxia-induced injury than PAEC. The depletion of cyclooxygenase activity and the resultant effect on PGI2 and PGE2 production may be a factor in the development of hyperoxia-induced endothelial injury. PMID- 8341724 TI - Eicosapentaenoic acid abolishes the proatherogenic effects of cholesterol: effects on migration of bovine smooth muscle and endothelial cells in vitro. AB - It is well known that vascular endothelial cell (EC) migration plays a major role in regeneration of the injured endothelium and also that smooth muscle cell (SMC) migration is the important step for atheromatous plaque formation. In the present study, we investigated the effects of cholesterol and eicosapentaenoic acid (EPA) on bovine carotid artery EC and SMC migration using the modified Boyden chamber technique. The migration activity of the cholesterol-enriched ECs loaded with cholesterol-rich liposomes was significantly suppressed, whereas that of the cholesterol-enriched SMCs was enhanced. Next, we examined the effects of EPA pretreatment on the migration of both cell types. When ECs and SMCs were treated with EPA (5 micrograms/ml) for 2 days, the EPA content increased from 0.55 +/- 0.04% to 11.72 +/- 0.19% and 1.22 +/- 0.09% to 9.69 +/- 0.07% in cellular phospholipids, respectively. Although pretreatment of the ECs with EPA caused a significant increase in serum-induced cell migration, pretreatment of SMCs had no effect. If both cell types were concomitantly pretreated with EPA and cholesterol rich liposomes, EPA abolished the effects of cholesterol on the migration of both cell types, but did not affect the content of cholesterol in both cells. These data indicate the possibility that EPA counteracts the atherogenic effect of cholesterol on EC and SMC migration. PMID- 8341725 TI - U 46619 induces different blood pressure effects in male and female spontaneously hypertensive rats (SHR). AB - The effect of U 46619 (5 micrograms/kg i.v.) alone or in combination with acetylsalicylic acid (ASA) (100 mg/kg po.) on mean arterial blood pressure (MABP) was investigated in male and female spontaneously hypertensive rats (SHR). In male SHR, a significant increase of MABP was observed 1 min after administration of U 46619. Pretreatment of male SHR with ASA delayed the increase of MABP after intravenous injection of U 46619 compared to U 46619 alone. Whereas in control animals the elevated MABP returned to baseline values 5 min after intravenous application of U 46619, the MABP of ASA-pretreated male SHR remained significantly increased by about 30 mmHg. In contrast, the MABP of female SHR did not respond to U 46619 alone or to the combination of U 46619 and ASA. Sex differences were further shown by the vascular formation of thromboxane B2 (TXB2). Whereas in male SHR the vascular formation of TXB2 was increased by U 46619, the TXB2 formation of female SHR was decreased. The vascular formation of 6-keto-PGF1 alpha of male and female SHR was not influenced by U 46619 alone or a combination of U 46619 and ASA. In conclusion, our results demonstrate that the blood pressure of SHR respond differently to the TXA2 mimetic U 46619 in the two sexes. Furthermore, by modulating blood pressure response to TXA2, vasoactive prostanoids may be significantly involved in the maintenance of hypertension with male SHR. PMID- 8341726 TI - Lipoproteins from normolipidemic and dyslipidemic subjects modify the thromboxane A2 generation by platelets in clotting human blood. AB - The study was performed to investigate the influence of lipoproteins (LP) on the thromboxane (TX) A2 formation capacity of platelets in clotting whole blood in vitro. The different lipoprotein fractions VLDL, LDL, HDL2 and HDL3 were isolated from blood of normo- or dyslipidemic volunteers by ultracentrifugation. These lipoproteins were incubated in blood with different levels of serum total cholesterol (TC) taken from normolipidemics (TC < 200 mg/dl), moderate hypercholesterolemics (TC: 200-250 mg/dl) or subjects with high cholesterol level (TC > 250 mg/dl), respectively. The amount of serum TXA2 formed within 60 min at 37 degrees C was measured by enzyme immunoassay. The results obtained show that the efficacy of separate LP fractions to influence the TXA2 production depends not only on the type of LP fraction but also on the source of plasma used for isolation of LP and on the cholesterol level in the blood for incubation: LDL taken from normolipidemics or moderate hyperlipidemics inhibited the TXA2 formation in blood from normolipidemics (P < 0.02, respectively), but enhanced it in blood from persons with moderate hypercholesterolemia (P < 0.05). LDL from hyperlipidemics enhanced TXA2 production in blood from hyperlipidemics (P < 0.05). The HDL2 fractions inhibited the TXA2 formation in blood from normo- and hypercholesterolemics (P < 0.02, resp.), but there was no effect of HDL2 in clotting blood from persons with moderate hypercholesterolemia. All HDL3 fractions tested inhibited the TXA2 formation in all types of blood used for clotting (P < 0.02, resp.), probably due to their great cholesterol accepting capacity. PMID- 8341727 TI - [Interaction of NO-generators with thioles]. PMID- 8341728 TI - Bridged bis(4-thiazolidinones) and related compounds with antibacterial activity. AB - Condensation of 4,4'-diaminobiphenyl ether (1) and 4,4'-diaminobiphenyl methane (6) with various aldehydes gave diarylidenebiphenyl ethers 2a-d and diarylidenebiphenyl methanes 7a-c, respectively, which on cyclocondensation with merceptoacetic acid yielded 3,3'-[oxy-bis(4,1-phenylene)]-bis[(2-substituted phenyl)-4- thiazolidinones] 3a-d and 3,3'-[methylene-bis(4,1-phneylene)]-bis[2 substituted phenyl)-4-thiazolidinones] 8a-c. A series of 2,2'-[oxy-bis(4,1 phenylenenitrilo)]-bis[3- (substituted)-4-thiazolidinones] 5a and b and 2,2' [methylene-bis(4,1-phnylenenitrilo)]-bis[3-(substituted)-4- thiazolidinones] 10a and b were synthesized from 4,4'-diaminobiphenyl ether (1) and 4,4' diaminobiphenyl methane (6) via the corresponding dithiocarbamide biphenyl ethers 4a and b and dithiocarbamide biphenyl methanes 9a and b by cyclocondensation with monochloroacetic acid. The structures of compounds 2-10 are supported by elemental analysis and spectral data (IR, 1H NMR, 13C NMR). The specific rotation of compounds 3c, 8b and 8c was measured. PMID- 8341729 TI - Synthesis and biological activity of mono- and bis-hydrazones of cyclic aminoguanidines. PMID- 8341730 TI - Mathematical model of the cut-off effect in the homologous series of tertiary amine local anesthetics. AB - It is proposed a simple mathematical model explaining the quasi parabolic dependence of the local anesthetic activity on the length of hydrophobic substituent in the homologous series of tertiary amines (TA). It is suggested that the molecules of TA intercalate between the lipid molecules in bilayers. Due to the mismatch between the lengths of lipid and TA hydrocarbon chains the intercalation results in a decrease in the bilayer thickness. The quasi parabolic dependence is the result of combination of partition equilibria and of geometrical parameters of interacting molecules in the bilayer. The model predicts that the TA chain length at which the maximum activity is observed should be dependent on the lipid: aqueous phase volume ratio. The empirical parameters used in the model are obtained from the X-ray diffraction on multilamellar egg yolk phosphatidylcholine (EYPC) dispersions with the monohydrochloride of [2-(heptyloxy)phenyl]-2-(1-piperidinyl)ethyl ester of carbamic acid and from the partition equilibria of its alkyloxy homologs with unilamellar EYPC liposomes. PMID- 8341731 TI - Synthesis and local anaesthetic activities of 3-(2 alkoxyphenylcarbamoyloxy)chinuclidinium chlorides. PMID- 8341732 TI - [The penetration of liposomal encapsulated vitamin A and E in the skin]. PMID- 8341733 TI - Transport of testosterone through rat skin from transdermal patch formulations. PMID- 8341734 TI - [Skin pH value on hands after application of soap, cleaners and hand disinfectants]. PMID- 8341735 TI - Influence of propranolol enantiomers on the pentetrazol kindling development in rats. PMID- 8341736 TI - Correlation between log k', C, pi, RF, RM, Pex, Pcal and values of surface and infiltration anaesthesia for piperidinoethylesters of alkoxy substituted phenylcarbamic acid series. Part 109(3): Study of local anaesthetices. PMID- 8341737 TI - The anatomy of Cupid's bow in normal and cleft lip. AB - This is a gross and microscopic examination of the cutaneous-vermilion-mucosal region (Cupid's bow) in infants with normal lip as compared to cleft lip. Morphologic observations of lips in situ were made with magnification. Specimens for histology were from the normal upper lip of infants (n = 3) and adults (n = 4), and from redundant tissue made available during primary repair of cleft lip (n = 13) and cleft lip revision (n = 4). Tissues were analyzed with hematoxylin and eosin, Gomori trichrome, and Fontana-Masson stains. Immunoperoxidase stains were used to emphasize vascular endothelium and epithelial cytokeratins. Our observations support the hypothesis that the anterior projection of the pars marginalis of the musculus orbicularis oris gives rise to the normal cutaneous vermilion junction ("white skin roll" of Gillies-Millard). The band of vellus hairs, found atop the vermilion-cutaneous junction, also highlights the rim of Cupid's bow. There was no abrupt alteration in vasculature, melanin, or cytokeratin content in the white roll. Proceeding caudally, the vermilion-mucosal region was characterized by progressively increasing epidermal thickness and size of rete ridges, decreasing melanin, more superficial capillaries, and an abrupt transition from keratinized to nonkeratinized squamous epithelium ("red line" of Noordhoff). In the cleft lip specimens, where white roll was absent, there was hypoplasia and disorientation of the underlying pars marginalis component of m. orbicularis oris. Vellus hair follicles were seen in the zone of presumptive white roll in clefts, just as in normal lip. Frequently, these pilar units contained disproportionately large sebaceous glands. In some cleft lip specimens, ectopic sebaceous glands were noted in the oral mucosa. We also observed a deficiency of vermilion width on the medial side of unilateral cleft lip, whereas the width of the vermilion at the crest of the bow was normal or slightly increased in the lateral cleft segment. A narrow vermilion band and exposed hypoplastic mucosa were characteristic of the prolabium in the bilateral complete cleft deformity. The findings of this study are pertinent to technical details for construction of the Cupid's bow and vermilion in unilateral and bilateral cleft lip. PMID- 8341738 TI - The role of the dura in cranial bone regeneration in the immature animal. AB - In an animal model, the effect of transferring mature pericranial tissues to immature animals with cranial bone defects was tested. Isogeneic guinea pigs of different ages were used: "infants" (3-4 weeks) and "adults" (> 18 months). Bilateral parietal cranial defects were made in infant guinea pigs and the guinea pigs were divided into three groups. In group 1 (n = 6), the infant periosteum was resected and replaced as an autograft on one side (control), and adult periosteum was transplanted as an isograft on the other (experiment). In group 2 (n = 5), dura was used as the variable. In group 3 (n = 5), combined dura and periosteum were the variables. After 8 weeks, there was complete or near complete bone regeneration in all animals in which infant dura was present. There was minimal to no bone regeneration in defects in which adult dura was present. Unlike dura, periosteum had little influence on the capacity of the bone to regenerate. PMID- 8341740 TI - Free anterolateral thigh flaps for reconstruction of head and neck defects. AB - The anterolateral thigh flap is a septocutaneous artery flap based on the septocutaneous or muscle perforators of the lateral circumflex femoral system. Little has been reported about the variations in its vascular anatomy and its application for head and neck reconstruction. We report 22 cases in which this flap was used for the reconstruction of head and neck defects. Based on our clinical and cadevaric experiences, the derivation of the vascular pedicle of this flap has four variations by which the septocutaneous perforators are derived from the descending branch of the lateral circumflex femoral system and/or from the transverse branch of that system, or for which there are no septocutaneous perforators but there are muscle perforators originating from the lateral circumflex femoral system. Clinically, the vascular variations and the locations of perforators of this system can be determined preoperatively with stereoangiograms or simple angiograms and Doppler audiometry. The anterolateral thigh fasciocutaneous flap is suitable for reconstruction of defects in an oral floor with tongue and esophageal deficits, scalp defects with dural defects, and for large full thickness defects of the lip. The advantages of this flap are safe elevation, a long and wide vascular pedicle, skin that is generally thin, and good pliability. Even if the skin is thick, a thinner flap can be created by sacrificing a large amount of fatty tissue. Furthermore, the skin territory is very wide and long. The donor defect can often be closed directly with its scar being less noticeable. The disadvantage of this flap is that the anatomy of the pedicle vessels has irregular derivation from the main vessels. This can be overcome, however, by employing preoperative stereoangiograms. PMID- 8341739 TI - Free combined composite flaps using the lateral circumflex femoral system for repair of massive defects of the head and neck regions: an introduction to the chimeric flap principle. AB - Chimeric composite flaps combined using microanastomoses consist of two or more flaps or tissues, each with an isolated pedicle and a single vascular source. Free combined chimeric flaps using the lateral circumflex femoral system were used to treat massive composite defects of the head and neck in 10 cases. A combined anterolateral thigh flap and vascularized iliac bone graft based on the lateral circumflex femoral system and the deep circumflex iliac system was the most commonly used combination. An anteromedial thigh flap and a paraumbilical perforator-based flap were also combined with this principal combination. The advantages of this chimeric flap over other osteocutaneous flaps are: (1) The flap is relatively thin and the pedicle vessels are up to 10 cm longer and are wider than those of other flaps for easier harvesting of the flap. (2) It is unnecessary to reposition the patient. (3) The vascular pedicle to the skin can be separated from that of the bone. (4) The donor site is not close to the recipient site. (5) The donor scar is in an unexposed area. (6) The skin territory of this flap is extremely wide. (7) A combined anterolateral and anteromedial thigh flap and vascularized iliac bone graft can be easily obtained as an extended combined osteocutaneous flap. (8) Other neighboring skin flaps, such as a groin flap, a paraumbilical perforator-based flap, or a medial thigh flap, can be combined with this chimeric flap because several major muscle branches to be anastomosed derive from the lateral circumflex femoral system. Chimeric composite flaps using the lateral circumflex femoral system are considered suitable for the repair of massive composite defects of the head and neck. PMID- 8341741 TI - Osteocartilaginous flap technique for acquired and congenital saddle nose deformities. AB - This paper illustrates the objective possible applications of the osteocartilaginous flap technique in solving the functional and aesthetic problems associated with saddle nose deformities, the pathogenesis of which essentially relates to: (1) congenital saddle noses; (2) post-traumatic saddle noses; and (3) saddle noses resulting from previous surgery on the septum. This technique is suggested as an alternative to a combination of other methods (such as septoplasty, bone, or cartilage grafts) to restore the inhalatory function of the internal nasal valve and the integrity of the nasal support structures using locally available tissues. The authors prefer to use this technique in the treatment of serious congenital or acquired saddle nose deformities and to assign composite grafts a supplementary function only. The different stages of this surgical procedure are analyzed and the results are assessed during short- and medium-term follow-up. PMID- 8341742 TI - Submental lipectomy with skin excision. AB - A new method of excision of submental skin and fat with modified Z-incision affords easy excision, wide exposure, and simple closure. Thirty-two patients over an 18-year period have had satisfactory results with inconspicuous scars. Modification of platysma muscles and subplatysmal fat excision are facilitated by the wide exposure. Use of this method has been limited to those cases in which a large submental fold is present in a patient who declines to have a regular rhytidectomy or in cases of residual submental redundancy after a complete rhytidectomy. Occasionally, a rhytidectomy is not sufficient. PMID- 8341743 TI - Osseointegrated implants: a comparative study of bone thickness in four vascularized bone flaps. AB - Primary and secondary reconstruction of mandibular continuity defects with vascularized bone is currently the standard of care at many institutions. The most commonly utilized donor sites for such bone flaps include the scapula, iliac crest, fibula, and radius. Recently, interest has grown in the placement of osseointegrated implants into these flaps to facilitate functional dental rehabilitation. There are no studies comparing the bone available from each of these flaps into which osseointegrated implants can be placed. In this cadaver study, the dimensions of bone available for implant placement from the iliac crest, scapula, fibula, and radius osseous flaps were measured. The iliac crest and fibula flaps had bone dimensions consistently adequate for implant placement. Bone available for the safe placement of implants into the scapula flap was found in the majority of specimens. The radius flap group had the highest number of specimens that were inadequate for implant placement. The majority of the specimens with bone inadequate for implantation were from females. Clinical implications of this study regarding flap selection are discussed. PMID- 8341744 TI - Dermatofibrosarcoma protuberans of the chest and the shoulder: wide and deep excisions with immediate reconstruction. AB - Dermatofibrosarcoma protuberans is a rare malignant tumor of the skin. The only satisfactory treatment is surgical and consists of a wide excision. In our department, we have established the limits of the excision required to be a margin of 5 cm on the surface, whereas in the depth, we excise the first healthy anatomical structure encountered. Latissimus dorsi flap reconstruction was used for the major tissue deficit for 15 patients with dermatofibrosarcoma protuberans of the chest and the shoulder. When compared to skin grafting, this technique results in an improved aesthetic appearance and a stable cover for the periosteumless clavicle. Fourteen patients were followed for an average of 37.6 months and all remained free of disease. PMID- 8341745 TI - A new approach to the study of skin vascularization. AB - There are several methods of quantifying the vascularization of tissues, including the skin, but they are imprecise in terms of quantification of the complexity and structure of vascular networks. Fractal analysis can quantify the complexity of any structure existing in nature by using fractional dimension. This study makes a case for this approach by demonstrating the fractal structure of the skin vascular network in the mouse. The skin was removed from the posterior face of the thigh, which is supplied by a musculocutaneous perforator system. Twenty arterial vascular networks were investigated by image analysis and the fractal dimension was determined by the box counting method. Statistical analysis revealed an average mean of fractal dimension D = 1.256 (SD = 0.086), indicating low to intermediate complexity with a narrow distribution of results. D should logically fluctuate within a certain limit, depending on the anatomical structure investigated and its physiological function. These results demonstrate the ability of fractal analysis to quantify the vascular pattern of the skin. Fractal analysis opens a new field of investigation in the study of vascularization patterns and possible vascular modification by different physiological or pathological conditions (flap-delay techniques, tobacco use, diabetes mellitus, classification of diabetic retinopathies). PMID- 8341746 TI - Adjuvanticity and arthritogenicity of silicone. AB - Potential adjuvanticity and arthritogenicity of silicone obtained from a mammary implant were investigated. Silicone, injected intraperitoneally in conjunction with heat-killed Mycobacterium tuberculosis and EL4 cells (mouse tumor cell, H 2b), failed to enhance the development of immune response directed toward EL4 cells in Lewis rats. Subplantar injection of silicone, alone or in combination with heat-killed M. tuberculosis, also failed to induce adjuvant arthritis in Lewis rats. These findings suggest that silicone has neither adjuvant activity nor arthritogenic property and is not an effective substitute for the mineral oil component of Freund's adjuvant. PMID- 8341747 TI - Soft tissue response to textured silicone implants in an animal experiment. AB - In a study on rats to assess soft tissue response to textured silicone implants, ellipsoid 15 x 20 mm pieces from the bag of a Biocell breast prosthesis were implanted under the dorsal skin. Histological examinations including immunohistochemical detection of myofibroblasts were made 2 weeks and 1, 3, 6, and 8 months after implantation (12 specimens for each time interval). On the smooth side of the implant, which served as a control, the thin connective tissue capsule characteristically seen with silicone elastomer implants developed within a month. Myofibroblasts were present after the first month and appeared to reach a peak 3 months after implantation, after which they showed marked regression. On the textured side of the implant, villous processes were a characteristic feature of the capsules; originating in a common basal layer, they penetrated into the cavities of the implant. Collagen deposits and myofibroblasts only became more evident during the third month after implantation; they were limited to the common basal layer of the capsule, though foreign body reaction persisted in the villous processes until the end of the experiment. The experimental study, limited to an 8-month period after implantation, showed that texturing of the implant surface prevents compact capsule development and considerably delays or inhibits the maturation process. PMID- 8341748 TI - Ultraviolet-A induced delayed wound contraction and decreased collagen content in healing wounds and implant capsules. AB - Chronic exposure to ultraviolet-A radiation causes changes in the biochemistry of dermal connective tissue. To investigate its effects on wound healing, we irradiated Sprague-Dawley rats for 4 months using a black ray ultraviolet-A radiation source (560 J/cm2). Full thickness skin wounds of 2 cm in diameter were then created on the back of each animal and silicone cubes were implanted subcutaneously into the irradiated area of the back. Wound contraction in the irradiated animals (n = 28) was significantly slower than that of the controls (n = 29) (p < 0.001). Postoperatively, the hydroxyproline content of the contracted wounds and the implant capsules was assessed at 6 and 12 weeks, respectively. In the irradiated animals, it was found to be significantly less than that of the controls (p < 0.001). A delay in wound contraction and a decrease in hydroxyproline content of healing wounds and implant capsules, reflecting an alteration in collagen metabolism, are two effects of prolonged intermittent ultraviolet-A radiation pretreatment. PMID- 8341749 TI - Microsurgical management of extremity wounds in diabetics with peripheral vascular disease. AB - Plastic surgeons are frequently called upon to evaluate wounds in diabetic patients with compromised vascular inflow. Although a few authors have reported success in coverage of such wounds with microsurgical techniques, enthusiasm for this procedure has remained low due to concerns about flap viability, occlusion of flow to the distal limb, and the usually poor systemic status of such patients. We report here on our experience with 19 diabetic patients with peripheral vascular disease and a nonhealing wound of the lower extremity treated over the last 4 years with microvascular tissue transfer. Two patients (10.5 percent) suffered anastomotic difficulties and there was one flap loss (5 percent). Major morbidity rates were acceptable, with only one perioperative death (5 percent) and three cases of nonfatal major systemic difficulties in the immediate postoperative period (16 percent). Despite the importation of well vascularized tissue, local morbidity at the recipient site was seen in nine patients (47 percent). The overall limb salvage rate was 72 percent during the period of follow-up, which averaged 22 months. Despite this loss of five limbs, all but three of the patients eventually returned to ambulation. The overall death rate in our series was only 2/19 (10.5 percent) over the period of follow up. Although further work needs to be done in this difficult group of patients to ascertain the long-term benefit (especially relative to the cost/benefit ratio), we feel that this series confirms the safety and short-term efficacy of microsurgical treatment of such individuals. PMID- 8341750 TI - Selection of topical antimicrobial agents for cultured skin for burns by combined assessment of cellular cytotoxicity and antimicrobial activity. AB - Cultured epidermal skin has become an adjunctive therapy for treatment of major burn injuries, but its effectiveness is greatly limited due to destruction by microbial contamination. To evaluate candidate drugs for use with cultured skin, a combined cytotoxicity-antimicrobial assay system was developed for determination of toxicity to cultured human keratinocytes and fibroblasts, and to common burn wound organisms (20 bacterial and 4 fungal strains). Candidate agents including Hibiclens (n = 3), amikacin, piperacillin, norfloxacin, and nystatin were tested separately and in combination (n = 6 each) for inhibition of growth of human cells and lytic activity on microorganisms in the wet disc assay. The data showed that: (1) Hibiclens was uniformly toxic to both cultured human cells and microorganisms; (2) norfloxacin had dose-dependent toxicity to human cells and broad effectiveness against microorganisms; and (3) norfloxacin (25 micrograms/mL) plus nystatin (100 U/mL) had low toxicity to human cells and high toxicity to both Gram-positive and Gram-negative bacteria (20 of 20) and fungi (4 of 4). Selection of topical antimicrobial drugs by these assays may improve effectiveness of cultured skin for burns and may be extended to the control of other surgical wound infections. PMID- 8341752 TI - Extensor digiti minimi tendon transfer to prevent recurrent ulnar drift. AB - Thirty percent of patients with rheumatoid arthritis develop ulnar drift. Although numerous operations have been described, recurrence of the deformity is frequent. We recommend use of the extensor digiti minimi tendon transfer to prevent recurrent ulnar deviation. The tendon insertion is moved from a dorsal location to a dorsal-radial position. In this new location, the tendon produces both extension and radial deviation. Moreover, this transfer is maximally effective in extension when ulnar drift is greatest. We have used this transfer 28 times during the past 6 years. In evaluating patients more than 1 year after surgery, metacarpal phalangeal joint extension averaged 52 degrees and there was no evidence of recurrent ulnar drift of the little finger. The only problem was slight hyperextension of less than 5 degrees in approximately half of the patients. However, in no patient was this functionally a problem. We recommend the use of this tendon transfer in all patients with ulnar drift undergoing metacarpal phalangeal joint replacement for rheumatoid arthritis. PMID- 8341751 TI - The second dorsal metacarpal flap with vascular pedicle composed of the second dorsal metacarpal artery and the dorsal carpal branch of radial artery. AB - A pedicle second dorsal metacarpal flap, comprising the second dorsal metacarpal artery, the partial carpal arterial arch of the dorsal hand, and the dorsal carpal branch of radial artery, was designed. The flap may be rotated through two axes of rotation, one at the entry of carpal branch of radial artery into the first dorsal interosseous muscle and one at the entry of the recurrent cutaneous branch arising from the second dorsal metacarpal artery into the skin. The method introduced can increase as much as possible the length of the vascular pedicle of the second dorsal metacarpal flap. Thus, it can cover a small defect at a more distant area. If the width of this flap is not more than 3 cm, the donor site can be closed directly. The flap had been used in five cases with no necrosis of the flap or complication of the donor site. In further investigation of the postoperative patients, no stiffness and tightness have been observed through a short period of rehabilitation of the hand. The results are satisfactory. The anatomy, the operative technique, and three selective cases are described here. PMID- 8341753 TI - Verification of a free vascularized nerve graft model in the rat with application to the peripheral nerve allograft. AB - We report a vascularized sciatic nerve graft in the rat, based upon the femoral popliteal superior muscular artery pedicle. The pedicle may be raised from the common femoral artery via the popliteal artery, with accompanying venous drainage to the femoral vein. We have characterized two vessels: the middle tibial artery to the posterior tibial nerve and the arteria comitas nervus peroneus to the peroneal nerve. Plastic monomer and Evans blue labeled albumin injections established the anatomic model. The graft was reliably perfused at the time of isolation and 24 hours post-transplantation. The model was used to evaluate regeneration across allogeneic (ACI to Lewis, n = 12) versus syngeneic (Lewis to Lewis, n = 6) nerve grafts. Electrophysiologic and histomorphometric assessments demonstrated that the vascularized immunosuppressed allograft was similar to the vascularized syngeneic graft. Both were superior to the vascularized allograft without immunosuppression. PMID- 8341754 TI - The law poster and what it has done for me. PMID- 8341755 TI - Familial subungual keratoacanthoma in association with ectodermal dysplasia. AB - Described is the first report of familial SUKA, occurring in two of three sisters with ectodermal dysplasia, a rare, hereditary disorder involving ectodermally derived organ systems. Although rare, SUKA should be considered when assessing rapidly growing nailbed lesions. Differentiation from subungual squamous cell carcinoma is essential. Tumor excision and curettage and close postoperative follow-up are recommended, with conservative amputation reserved for tumor recurrences. If the diagnosis of SUKA is confirmed in a female, an association with ectodermal dysplasia should be sought. PMID- 8341756 TI - Aspergillosis complicating the grafted skin and free muscle flap in a diabetic. AB - A case of infected diabetic foot ulcer was reconstructed by a free muscle flap overlaid with a skin graft. Primary cutaneous aspergillosis involving the grafted skin and the transplanted muscle was described. The patient presented with an indurated grey-yellow plaque or black eschar in the wound without purulent discharge. Biopsies and cultures demonstrated A. flavus as the etiologic agent without evidence of systemic dissemination. Early diagnosis necessitates a high index of suspicion in immunocompromised patients with unusual cutaneous manifestation. Treatment consisted of aggressive debridement, systemic and local antifungal therapy, and delayed grafting. We concluded that primary cutaneous aspergillosis may occur at the reconstructed wound in an immunocompromised diabetic, and that it is a rare complication requiring prompt diagnosis and treatment. PMID- 8341757 TI - Replantation of the heel pad. AB - A heel microvascular replantation was done to a 17-year-old patient. The replanted heel survived completely. A year after the operation, the patient is working in agriculture and has no problem walking. PMID- 8341758 TI - The lines and grooves of the face: a suggested nomenclature. AB - The lines and grooves of the face commonly recognized and used by plastic surgeons, biological anthropologists, forensic medicine specialists, artists, and others are described. Proper Latin anatomical names for them are suggested. It is hoped that eventually these will be adopted by those who use them and published by the International Anatomical Nomenclature Committee. PMID- 8341759 TI - Paired five-flap Z-plasty. AB - Web-like contractures may occur along both the outer borders of joints, creating double-parallel contracture bands that turn into webs during movements. A combination of two "five-flap z-plasties" lying in confrontation to each other was used to release such contractures. The two Vs face each other and meet at their upper ends, forming a rhomboid (Fig. 1, a and b) or hexagon (Fig. 1, c and d) whose position remains unchanged after the contractures have been released and all the flaps transferred or advanced. This method has been used to release a total of seven double-parallel web-like linear contractures with very satisfactory results. Paired five-flap z-plasty seems to be superior when release of double web-like contractures, with the presence of sufficient spared skin, is contemplated. PMID- 8341760 TI - Recurrence of leukemia cutis within a cutaneous microvascular transplant. PMID- 8341761 TI - Elevator modification: enhancement for safety and confidence during orbital exploration. PMID- 8341762 TI - Dealing with the ruptured silicone gel breast implant. PMID- 8341763 TI - Could tight breast capsules "squeeze" a significant amount of silicone gel out of an implant? PMID- 8341764 TI - Serotonin2 receptor binding in blood platelets of schizophrenic patients. AB - Platelet serotonin2 (5-HT2) binding was determined in 47 neuroleptic-free schizophrenic patients and 42 normal control subjects. Although the maximum number of 5-HT2 binding sites (Bmax) was significantly higher in the blood platelets of schizophrenic patients than in those of the normal control subjects, the difference disappeared after correction for age and sex effects. However, the Bmax of schizophrenic patients who had made suicide attempts was significantly greater than that of schizophrenic patients who had not, as well as that of normal controls. There was no difference in Kd between the schizophrenic patients and control subjects, and no relation between Kd and suicide attempts. The importance of serotonin in schizophrenia and suicide attempts is discussed. PMID- 8341766 TI - Association of levels of N-acetyl-beta-glucosaminidase with specific psychiatric symptoms in bipolar patients. AB - The levels of N-acetyl-beta-glucosaminidase (NAG) in urine from 35 patients with bipolar affective disorder were compared with scores for the 90 items (symptoms) of the Symptom Checklist (SCL-90). There were significant negative correlations between NAG levels and 23 of the SCL-90 variables (symptoms). These symptoms could be grouped into the following categories: anxiety, unusual or psychotic thinking, suicidal thinking, dysphoria, irritability, nausea, headaches, memory problems, and loss of interest. Serotonin abnormalities may play a role in the production of many of these symptoms. The hypothesis that NAG could be a marker for a serotonin activity is discussed. PMID- 8341765 TI - Further evidence for the existence of endogenous serotonin uptake inhibitors and their purification by calmodulin affinity chromatography. AB - Experimental evidence suggests the occurrence of endogenous antidepressant-like compounds in the brain, blood plasma, and urine. After extensive purification by calmodulin-sepharose affinity chromatography, and further purification of the urine-derived sample by exclusion chromatography, at least three distinctive fractions have been identified. These fractions effectively inhibited serotonin uptake, imipramine, and/or paroxetine binding, and they apparently contained some compounds that were recognized by the anti-imipramine or anti-paroxetine antibodies. Their identification may have significant implications for studies of affective illness. PMID- 8341767 TI - Effects of single dose haloperidol administration on plasma homovanillic acid levels in normal subjects. AB - Homovanillic acid (HVA), an oxidative metabolite of dopamine, has been shown in a number of studies to reflect severity of symptoms and to predict response to neuroleptic treatment in schizophrenic patients. In several clinical studies, HVA levels have been shown to have a positive relationship with symptom severity and to decline over time upon treatment with antipsychotic agents. The magnitude of this decline appears to be related to the degree of symptom reduction in patients so treated. However, administration of dopamine postsynaptic antagonists should be expected to increase synaptic dopamine availability, thereby increasing HVA concentrations, according to traditional models of drug action. While in some studies, this appears to be the case, we saw no evidence of an early phase of HVA elevation after administration of 4- and 10-milligram doses of haloperidol to human volunteers. Rather, HVA levels declined during the period of absorption and attainment of peak haloperidol levels. Baseline HVA levels of 51.6 +/- 3.83 pmoles/ml and 56.8 +/- 5.70 pmoles/ml (after 4 mg and 10 mg., respectively) declined to minima of 35.6 +/- 1.67 pmoles/ml and 26.3 +/- 5.34 pmoles/ml respectively, at 3-4 hours after haloperidol administration. A trend was noted for the 10-mg dose to produce a greater decline than the 4-mg dose, which was most apparent at 4 hours after drug administration. The shape of both curves did not appear to be substantially different than expected on the basis of diurnal variation. These preliminary findings support the concept that dopamine turnover in humans is not increased and may be decreased by short-term administration of conventional neuroleptics. PMID- 8341768 TI - Personality and benzodiazepine sensitivity in anxious patients and control subjects. AB - Cloninger has recently proposed a model of personality variability that is based on three independent heritable traits of harm avoidance, novelty seeking, and reward dependence, each of which is thought to be mediated by a separate neurochemical and neuroanatomic mechanism. The current study tested hypotheses generated on the basis of this theory in anxious patients and control subjects. Eighteen patients with panic disorder, 12 patients with generalized anxiety disorder, and 21 control subjects underwent both personality testing and assessment of their sensitivity to diazepam, as measured by slowing of saccadic eye movement velocity. As expected, anxious patients displayed higher harm avoidance scores than controls. Although an inverse correlation between harm avoidance and benzodiazepine sensitivity was predicted, no relationship between these variables was found in any diagnostic group. However, a significant correlation was found between novelty-seeking scores and sensitivity to diazepam. This finding, although not predicted by Cloninger's theory, is consistent with prior preclinical and human studies. PMID- 8341769 TI - Hypercortisolemia and hippocampal changes in depression. AB - Hypercortisolemia is a frequently observed abnormality in patients with major depression. It has been hypothesized that the hippocampus, as a major feedback site for glucocorticoids, is involved in the pathophysiology of hypercortisolemia. Some have in fact posited that the hippocampus is marked by diminished size in depressed patients with hypercortisolemia. We tested this hypothesis by examining the relationship between hippocampal volume, assessed with magnetic resonance imaging, and hypercortisolemia using the dexamethasone suppression test (DST) in a group of 19 depressed patients. No differences in hippocampal volume were observed between patients and control subjects (n = 30). Within the patient group, DST suppressors did not differ from DST nonsuppressors in hippocampal volume. However, a relationship between hippocampal volume and 11 p.m. cortisol concentration was observed after covariance adjustment for age and sex. Furthermore, significant negative correlations were observed between hippocampal volume and both age of depressive onset and number of hospitalizations. The results of this study therefore provide limited support for the hypothesis regarding an essential role of the hippocampus in the neuroendocrine elevation of glucocorticoids in depression. PMID- 8341770 TI - Magnetic resonance abnormalities in HIV infection: a study in the drug-user risk group. AB - Cognitive impairment is a frequent complication of advanced human immunodeficiency virus-1 (HIV-1) infection. However, structural imaging of the brain has not revealed abnormalities that precede the onset of clinical abnormalities. Cranial magnetic resonance (MR) studies were performed in 28 male subjects with intravenous drug use histories; nine were HIV-1 seronegative, 11 were HIV-1 seropositive but asymptomatic, and eight were seropositive and met symptomatic criteria for acquired immune deficiency syndrome (AIDS). Cortical atrophy, but not the degree of ventricular enlargement or signal abnormalities, was increased in the seropositive group compared with the seronegative group and also differed between asymptomatic seropositive and seronegative patients. An increased level of cortical atrophy may reflect the early impact of HIV-1 infection on the brain. PMID- 8341771 TI - Hyperdopaminergia in schizophreniform psychosis: a chronobiological study. AB - Circadian rhythm abnormalities have been described in various psychiatric disorders, but they have not received much attention in studies of schizophrenia and schizophreniform psychosis. The present study used the cosine model to determine the circadian patterns of amino acids, dopamine, and prolactin concentrations, which were analyzed over a 24-hour period in serum of healthy subjects, drug-free schizophrenic patients, and neuroleptic-treated schizophrenic patients. The mesor (the daily mean) of phenylalanine was lower in drug-free schizophrenic women than in healthy women. The mesors of the ratio of phenylalanine or tyrosine to competing amino acids were similar in healthy subjects and patients. The ratio of phenylalanine/competing amino acids showed a phase advance (i.e., earlier onset of the time of highest concentration) in drug free patients compared with healthy subjects. Schizophrenic patients displayed a higher dopamine mesor than healthy subjects. Female drug-free schizophrenic patients had lower prolactin mesors and lower amplitudes (i.e., half of the total predictable change in rhythm) than healthy women. Compared with healthy subjects, schizophrenic patients showed a phase advance of circadian prolactin concentrations. Neuroleptics raised the prolactin mesor and amplitudes but did not elicit any phase change in amino acids, dopamine, or prolactin. These data confirm the indirect pharmacologic evidence of increased dopaminergic activity in schizophrenic patients that relates to dopamine's precursors and to the neuroendocrine regulation of prolactin. PMID- 8341772 TI - Disease prevention through immunization: the beginning of health care reform. PMID- 8341773 TI - The president's child immunization initiative--a summary of the problem and the response. AB - After only 24 days in office, President Bill Clinton announced a comprehensive childhood immunization initiative designed to assure that all children in the United States lead healthier lives by receiving age-appropriate immunizations against preventable diseases such as polio, mumps, measles, whooping cough, and diphtheria. As part of his economic stimulus proposal, the President requested $300 million for Fiscal Year 1993 to reinforce the nation's immunization infrastructure by providing funding for communities to extend clinic hours, provide more staff, and increase information and education efforts and for the planning and implementation of a national immunization tracking system. In its Fiscal 1994 budget request, the Administration asked for a doubling of the Centers for Disease Control and Prevention's immunization program funding to $667 million. In cooperation with key congressional committees, the Administration has also prepared legislation that would provide recommended childhood vaccines to States for free distribution to health care providers who serve children enrolled in Medicaid or who don't have health insurance that covers immunization services. Providers could not charge for the vaccine but could charge a fee for administration. State Medicaid programs would also be required to reimburse providers reasonably for vaccine administration. This measure is designed to improve universal access to immunization services by helping to remove financial barriers that impede children from being immunized at the appropriate age. PMID- 8341774 TI - Evaluation of telephoned computer-generated reminders to improve immunization coverage at inner-city clinics. AB - The authors evaluated the effectiveness of computer-generated telephoned reminders used to raise the rates of on-time immunization among preschool-age children in two public clinics in Atlanta, GA. The overall effect of the intervention on immunization levels appeared to be minimal (crude relative risk = 1.07, 95 percent confidence interval = 0.78, 1.46), in part because only about 80 percent of children in both the randomly selected intervention group and in the control group were members of a household with a telephone number listed in clinic records. However, logistic regression analysis indicated that 36 of 68 children (52.9 percent) in the intervention group whose households were reached were vaccinated within 30 days of their due dates, compared to 31 of 75 children (41.3 percent) in the control group whose household telephone numbers were recorded but not called (adjusted odds ratio = 2.12, 95 percent confidence interval = 1.01, 4.46). This analysis indicates that telephoned reminders demonstrated a level of effectiveness in improving immunization levels at inner city clinics that recommends further trial and study. PMID- 8341775 TI - Evaluation of a two-dose measles, mumps, and rubella vaccination schedule in a cohort of college athletes. AB - Despite high vaccination levels, measles outbreaks continue to occur among vaccinated adults. In response, new guidelines call for two doses of measles vaccine. To determine seroprevalence and response to vaccination in seronegative persons, we tested serums from 256 college athletes at a Maryland State college by enzyme-linked immunosorbent assay, vaccinated seronegatives, then re-tested vaccinees. High school records were obtained for persons seronegative to measles. Of 256 students, 53 (21 percent) were seronegative to measles alone, 13 (5 percent) were seronegative to rubella alone, and 5 (2 percent) were seronegative to both. Among those seronegative to measles, 86 percent had previously received a dose of measles vaccine. After vaccination, 37 persons initially seronegative to measles and 9 seronegative to rubella were 97 percent and 100 percent seropositive, respectively. The high measles seroconversion rate suggests that the two-dose vaccine schedule should effectively control campus measles outbreaks and, if given as measles-mumps-rubella vaccine, will also improve immunity to rubella and mumps. PMID- 8341776 TI - An epidemiologic investigation of a rubella outbreak among the Amish of northeastern Ohio. AB - From April 1990 to April 1991, 278 cases of rubella were reported to the Ohio Department of Health. Of these, 276 (99 percent) were among the Amish of northeastern Ohio. The outbreak involved eight counties in an area that contains large settlements of Old Order Amish. Members of this community of Amish frequently take religious exemption from recommended immunization practices and are believed to represent a high proportion of Ohio's rubella-susceptible persons. Vaccination history was known only for 146 of the Amish people. Of those, only four had a positive history of rubella vaccination. Of the 276 Amish with cases of rubella, 65 (24 percent) were younger than age 5 years, 104 (38 percent) were ages 5-14, 46 (17 percent) were ages 15-19, 32 (12 percent) were ages 20-29, 6 (2 percent) were ages 30 or older, and age was not reported for 23 (8 percent). The ratio of males to females with rubella was 1:1. Five women of the Amish community were pregnant; four had been ill with symptoms consistent with rubella. Three were in their first trimester. Congenital rubella syndrome did not occur in any of the four live births. Serology was available for only the two non-Amish people, and both were acute phase serum-positive for Immunoglobulin M. PMID- 8341777 TI - Pneumococcal vaccination in a remote population of high-risk Alaska Natives. AB - In response to an increasing prevalence of serious pneumococcal disease among adult Alaska Natives of northwest Alaska, a 3-year program was begun in 1987 to identify residents of that remote region who were at high risk for developing invasive pneumococcal disease, to determine their pneumococcal vaccination status, and to deliver vaccine to at least 80 percent of those at risk. After reviewing public health nursing and Indian Health Service data bases, the authors identified 1,337 persons, 20 percent of the 6,692 residents of the region, at high risk for invasive pneumococcal infection, defined either by having a specific chronic disease or by age criteria. Cardiovascular disease and alcoholism were the two most common chronic diseases. Only 30 percent of those determined to be at high risk had received one or more doses of pneumococcal vaccine previously. Half of those persons had received their most recent vaccination 6 or more years earlier. The program used both customary and innovative methods to deliver 23-valent polysaccharide vaccine to 1,046 of those at high risk (78 percent), including 388 persons who were revaccinated. At the completion of the project, 1,123 persons, 84 percent of those at high risk, had received at least 1 dose. They included 1,088 persons, 81 percent of those at high risk, with vaccination within the previous 5 years as a result of the project, compared with a 15-percent rate prior to the vaccination phase of the project. The program demonstrated that high levels of vaccination against pneumococcal disease, exceeding Year 2000 objectives of 60 percent, are attainable in a remote rural Alaskan population. PMID- 8341778 TI - Risk factors for septicemia-associated mortality in older adults. AB - Septicemia is the 10th leading cause of death among older adults in the United States; its mortality rate has steadily increased over the past decades. Little is known about factors which predispose to septicemia mortality in the elderly. The authors investigated risk factors for septicemia-associated mortality in 10,269 older adults as part of a longitudinal study of three communities (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA). During 6 years of followup, 177 persons (3.2 per 1,000 person-years) had septicemia ICD9 038 (International Classification of Diseases, ninth revision) reported on their death certificate. In a multivariate proportional-hazards model, septicemia mortality was significantly (P < 0.05) and independently associated with age, male sex, history of diabetes, history of cancer requiring hospitalization, smoking one pack of cigarettes per day or more, not drinking alcohol in the year prior to baseline, disability in activities of daily living, cognitive impairment, and missing cognitive testing score. These factors might be useful in developing an at-risk population for testing septicemia treatment or prevention strategies in a community setting. Further investigation is needed to explain underlying mechanisms of increased risk of subsequent septicemia. PMID- 8341779 TI - Stroke mortality and its socioeconomic, racial, and behavioral correlates in Florida. AB - Stroke mortality is associated both with being black and with having low socioeconomic status. However, it is uncertain to what extent that increased risk is related to rates of behavior-related risk factors, such as hypertension, cigarette smoking, obesity, or alcohol consumption. The investigators performed an ecologic analysis to estimate the contributions of behavioral risks, socioeconomic status, and black race to regional variations in stroke mortality rates among persons 55-84 years of age in Florida. They used data from the 1980 census and from the Behavioral Risk Factor Surveillance System (BRFSS) for 1986 through 1988. Weighted multiple linear regression models indicated that regions in Florida with high stroke mortality rates were characterized by high prevalences of poverty, obesity, and hypertension. Although limited by its ecologic design, this study suggests that socioeconomic status and prevalence of behavioral risks contribute independently to interregional disparities in stroke mortality rates in Florida. BRFSS data, now available for more than 45 States, can be used to help clarify the relative contributions of behavioral and other risks to population-based mortality rates. PMID- 8341780 TI - Where and how adolescents obtain alcoholic beverages. AB - Patterns of acquisition of alcoholic beverages by underage youth were studied, using focus group methods with a sample of midwestern youth. Results showed that the alcohol initially used by those in their early teens is obtained from parents' stocks or from older siblings and friends. By the midteens, parties at which alcohol (usually beer) is readily available become the major source. In the mid to late teens, young people purchase alcohol from commercial alcohol outlets, despite the fact that 21 is the legal age for purchasing alcohol. Factors reported to increase the rate of successful alcohol purchases include female buyer, male seller, young seller, and convenience store outlet. Results of focus group interviews revealed the easy accessibility of alcoholic beverages to underage youth. Further investigation into patterns of underage access to alcohol is recommended, with results from the focus group study guiding the design of probability sample studies to assess their generalizability. PMID- 8341781 TI - Self-reported frequency of serum cholesterol testing, awareness of test results, and laboratory cholesterol values in two South Carolina communities. AB - Self-reported frequency of cholesterol testing and awareness of test results were collected from 5,246 adults 18 years and older in two semirural communities in South Carolina. Serum cholesterol was also measured for about 60 percent of this group. More than half of these persons had serum cholesterol values greater than 200 milligrams per deciliter (mg per dL) and 21 percent had values greater than 240 mg per dL. One-third of the population had had their cholesterol level measured within the past year; 40 percent reported that their cholesterol level had never been measured. Among persons whose cholesterol was 240 mg per dL or more, 39 percent reported that their cholesterol had never been measured or that they did not know if it had been measured, 37 percent reported that their cholesterol had been measured but that they were not told that it was high, and 18 percent reported that their cholesterol had been measured and that they were advised to reduce it. Among persons whose cholesterol was 200 mg per dL or more, and who reported that they had cardiovascular disease, 25 percent reported that they were advised to reduce their cholesterol. These results emphasize the need to increase the proportion of the population who have had their cholesterol level measured, who know their test results, and who have been properly counseled about the results. PMID- 8341782 TI - Lung cancer rates in the Hispanic population of Connecticut, 1980-88. AB - To identify lung cancer patients of Hispanic ethnicity, surnames in the Connecticut Tumor Registry were matched with the 1980 Spanish surname list of the U.S. Bureau of the Census. Also death certificates for women with lung cancer in the registry were examined to ascertain maiden names. For women Hispanic surnames in the registry were not good indicators of ethnicity; their sensitivity was only 58 percent when compared with the decedent's maiden name. Estimated age-specific incidence rates for lung cancer during the 1980-88 period among Hispanic men, using surnames in the registry, were lower than the rates for non-Hispanic men, as expected from studies of Hispanic mortality in the Northeast. The distribution of histologic types, including those most strongly associated with smoking, was similar for Hispanic and non-Hispanic men. Although estimated lung cancer mortality rates were low for Hispanic men defined by surname, higher standard mortality ratios for Puerto Rican-born versus other Hispanic men suggested heterogeneity in lung cancer death rates of the Hispanic population of Connecticut. Lung cancer incidence and mortality rates should continue to be monitored in the Hispanic population of Connecticut, in view of anticipated increases attributable to trends in smoking behavior, and interventions should be planned to counteract anticipated increases. PMID- 8341783 TI - Local health departments implement a theory-based model to increase breast and cervical cancer screening. AB - Su Vida, Su Salud/Your Life, Your Health is a community program to increase participation in breast and cervical cancer screening. This program illustrates the diffusion of an innovative outreach strategy from a research environment to two local health departments. The program uses A Su Salud, the communication model in which positive role models are featured in the media, and community volunteers who give positive social reinforcement. Local health departments in Galveston and Corpus Christi, TX, were selected to implement the model because of excessive mortality rates in the region and the departments' adequate level of resources and commitment. Over an 18-month period, 54 stories of role models appeared in the media in Corpus Christi, and 60 appeared in Galveston. There were 490 volunteers active in Corpus Christi and 279 in Galveston. Of 365 inquiries to the Corpus Christi program, 35 percent were from the Mexican American target group of women ages 40-70. Of 1,457 women who contacted the Galveston program, 9 percent were from the African American target group ages 40-70. Local health departments are well-suited to participation in cancer control research applications because they have direct access to high-risk populations and have the authority to institutionalize effective interventions. PMID- 8341784 TI - Traumatic occupational fatalities in South Carolina, 1989-90. AB - Death certificates for South Carolina for 1989 and 1990 were examined to identify deaths resulting from injury incurred in the workplace. There were 277 deaths in that category in the 2-year period, an average yearly rate for traumatic occupational fatalities of 8.84 per 100,000 workers. The groups of industries with the highest fatality rates were transportation-communication-utilities, construction, and agriculture-fishing-forestry. The leading causes of death were injuries from motor vehicle crash, homicide, and falls. The traumatic occupational fatality rate for men was about 13 times greater than that for women; however, a much higher proportion of women died from homicide on the job. The findings in general reflect trends reported in other studies. The death rates for workers in South Carolina for 1989-90, however, were higher than national averages for 1980-88. National data for 1989-90 were not available for comparison. The data suggest that more effective injury prevention efforts need to be applied to such causes of on-the-job injury as motor vehicle crash, homicide, and falls. Those three categories accounted for more than 56 percent of all traumatic occupational fatalities in South Carolina in 1989 and 1990. Motor vehicle crash prevention efforts particularly are needed in the transportation communication-utilities industries. The findings show that particular efforts need to be directed to the retail trade category for prevention of homicide and to the construction industry for prevention of falls. PMID- 8341785 TI - Deaths among the homeless in Fulton County, GA, 1988-90. AB - The circumstances surrounding the deaths of 128 homeless persons investigated by the Fulton County, GA, Medical Examiner's Office during the period 1988-90 and the demographic characteristics of the deceased were studied and analyzed. Emphasis was placed on cause and manner of death, unintentional injuries, and alcohol-related mortality. Ninety-eight percent of those who died were men, 55 percent occurred outdoors, 55 percent were due to natural causes, and 42 percent resulted from injuries, most of which were unintentional. The average age at death was 46 years, and 80 percent of those who died were found dead. Nearly half of the deaths (47 percent) were related to the acute or chronic effects of alcohol; the blood of 45 percent tested positive for ethanol; of that 45 percent, 75 percent had a blood ethanol concentration that exceeded 0.1 grams per deciliter. Mortality patterns among the homeless persons in the study were similar to those previously reported in Fulton County and in San Francisco, CA. Available data indicate that mortality prevention strategies for the homeless in Fulton County should target alcohol abuse and unintentional injuries. Further studies are needed to document regional mortality patterns of the homeless. PMID- 8341786 TI - Birth outcomes of Korean women in Hawaii. AB - Since the end of the Korean War, immigration of Koreans to the United States has increased rapidly. In 1990, 11.6 percent of all Asians in the United States were of Korean ethnicity, and it is projected that Koreans will outnumber all other Asian groups, except Filipinos, in the United States by the year 2030. Despite the growing size of this population, very little is known about their health status. This study, using 1979-89 Hawaii vital record data, investigates the relationship between maternal sociodemographic characteristics, prenatal care utilization factors, and birth outcomes among Koreans as compared with Caucasians. The ethnic term "Caucasian" is used in Hawaii's vital records and is synonymous with non-Hispanic whites. Korean mothers were more likely to be older and have lower educational attainment, and less likely to be adolescent, single, or to have received adequate prenatal care than Caucasian mothers. More than 80 percent of the Korean mothers were foreign born. Significantly higher risks for very preterm delivery (less than 33 weeks) and very low birth weight births were observed for Koreans as compared with Caucasians. Nativity had no effect on birth outcome in this population. The results of this study suggest that prevention of preterm birth is an important focus for improving pregnancy outcomes in this growing ethnic group. PMID- 8341787 TI - Prevalence of aortic aneurysms in the Twin Cities metropolitan area, 1979-84. AB - The discharge summaries for Minneapolis-St. Paul metropolitan area residents hospitalized during 1979-84 were reviewed for diagnoses of aortic aneurysms. Annual age-specific and age-adjusted sex-specific hospital discharge diagnosis rates were calculated for all aortic aneurysms, dissecting aortic aneurysms, thoracic aortic aneurysms (nondissecting), and abdominal aortic aneurysms (nondissecting). For each aortic aneurysm type, hospital discharge diagnosis rates were found to increase with age for both men and women. Abdominal aortic aneurysms were the most common type reported (age-adjusted annual rates for men varied between 40.6 and 49.3 per 100,000 population; for women, between 6.8 and 12.0 per 100,000 population). Men were noted to have higher rates for each aneurysm type. An increasing temporal trend was observed for all aortic aneurysms and abdominal aortic aneurysms among men. These findings are reviewed in light of recent data on mortality from aortic aneurysms in the United States. PMID- 8341788 TI - Do anti-smoking media campaigns help smokers quit? AB - As part of an evaluation of the 1990-91 anti-tobacco media campaign carried out by the California Department of Health Services, a study was conducted among 417 regular smokers who had quit during the period of the media campaign. In brief telephone interviews, all respondents identified up to three events or experiences that had influenced them to quit. In response to uncued questions, 6.7 percent of those interviewed indicated that they had been influenced to quit by an advertisement they had seen or heard on radio, television, or billboards. In response to direct questions about the media campaign, 34.3 percent of the respondents indicated that the media campaign's advertisement had played a part in their decision to quit. Applying the 6.7 percentage to the number of Californians who quit smoking in 1990-91, it can be estimated that for 33,000 former smokers, the anti-tobacco media advertisements were an important stimulus in their quit decision. Multiplying the 34.3 percent by the number of former California smokers who quit in 1990-91, the estimate of former smokers for whom the media campaign's advertisements played at least some part in their decision to quit rises to 173,000 persons. While causal attributions from such investigations should be made with caution, the evidence suggests that the 1990 91 campaign did influence substantial number of smokers in California to quit. PMID- 8341789 TI - Variability and consistency of rates of primary and repeat cesarean sections among hospitals in two states. AB - Hospitals in New York and Illinois have wide variations in their primary and repeat cesarean section rates. A number of factors account for these differences. To investigate whether hospitals with higher or lower rates tend to continue these patterns over time, their rates in 1988 were compared with those in 1983. It was found that a hospital's cesarean section rate was consistent, but some regression to the mean process did occur. By 1988, teaching hospitals had lower rates than nonteaching hospitals; this difference is likely due to the greater response to calls for increasing trials of vaginal birth after a previous cesarean section by teaching hospitals. Over time this should contribute to further moderating of the rates. Data were from the Illinois and New York State Departments of Health. PMID- 8341790 TI - NIAID mounts nationwide HIV-TB treatment study. PMID- 8341791 TI - NIAID to test new AIDS vaccines on pregnant women with HIV. PMID- 8341792 TI - AIDS history conference set for Oct. 28-29 at NIH. PMID- 8341793 TI - FDA clears the way for ending shortage of TB treatment drug. PMID- 8341794 TI - Nurses insist "fetus dead": "fetus alive" & catastrophe. PMID- 8341795 TI - Dr. improperly orders discharge: should nurse intervene? Case in point: NKC Hospitals, Inc. v. Anthony 849 S.W. 2d 564 KY (1993). PMID- 8341796 TI - MI: expert testimony--$1.3 million judgment: expert's qualifications issue. PMID- 8341797 TI - NY: siderails down--patient injured: hospital failed to comply with own rules. PMID- 8341798 TI - Loose "screw" left in patient: vicarious liability issue. Case in point: Hunnicutt v. Wright 986 F. 2d 119 MS (1993). PMID- 8341799 TI - Analysis of rice genes in transgenic plants. PMID- 8341800 TI - tRNA structure and aminoacylation efficiency. PMID- 8341801 TI - Evolution of Ca(2+)-dependent animal lectins. PMID- 8341802 TI - Immunoglobulin gene diversification by gene conversion. PMID- 8341803 TI - ADP-ribosylation factors: protein activators of cholera toxin. PMID- 8341804 TI - Molecular biology in the eicosanoid field. PMID- 8341805 TI - How tautological are interspecies correlations of carcinogenic potencies? AB - Crouch and Wilson demonstrated a strong correlation between carcinogenic potencies in rats and mice, supporting the extrapolation from mouse to man. Bernstein et al., however, show that the observed correlation is mainly a statistical artifact of bioassay design. Crouch et al. have a comeback. This paper will review the arguments and present some new data. The correlation is largely (but not totally) tautological, confirming results in Bernstein et al. PMID- 8341806 TI - Armitage-Doll two-stage model: implications and extension. AB - The objective of this paper is twofold: (1) to provide insight on the simplified MVK model of carcinogenesis (a model proposed by Moolgavkar and colleagues) by revealing the relationship between the Armitage-Doll two-stage model and the simplified MVK model; and (2) to extend the Armitage-Doll two-stage model to one with time-varying (piece-wise constant) parameters. It is shown that the simplified MVK model is a special case of the Armitage-Doll two-stage model, and many applications of the simplified MVK model involving intermittent exposures or exposures to different compounds in different time periods can be derived easily from the Armitage-Doll two-stage model with piece-wise constant parameters. The limitations of the Armitage-Doll two-stage model are discussed. PMID- 8341807 TI - The risks of licensing persons with diabetes to drive trucks. AB - The 1990 Americans with Disabilities Act forbids employers to bar disabled persons from jobs unless employers can show the disabled person cannot perform the tasks. The Federal Highway Administration will not license persons with diabetes mellitus to drive commercial motor vehicles in interstate commerce. These individuals may experience severe hypoglycemia, greatly increasing their risk of losing control of the truck. This prohibition is currently being reexamined. We describe the disease process leading to severe hypoglycemia and its physical manifestations. To quantify the risks of licensing persons with diabetes to use insulin, we first estimate the number of potential insulin-using drivers. We estimate that 1420 insulin-using persons would seek licenses in the United States if they were permitted to do so (920 noninsulin dependent and 500 insulin dependent). Next, we estimate the annual incidence of mild and severe hypoglycemia in these populations. The third step is to estimate the number of hypoglycemic episodes while driving. Estimating the likelihood of a crash due to a mild or severe hypoglycemic episode is the fourth step. We estimate that an additional 42 crashes each year would occur if insulin using persons were licensed to drive commercial motor vehicles in interstate commerce (20 from insulin dependent and 22 from non-insulin dependent drivers). PMID- 8341808 TI - Should persons with diabetes be licensed to drive trucks?--Risk management. AB - How should a regulatory agency interpret a risk analysis that concludes there is a small increase in risk? The agency must decide on behalf of society whether the increased risk is large enough to justify banning the risky activity or taking some other step to lessen the risks. In a companion paper (Songer et al.), we conclude that licensing insulin using persons to drive commercial motor vehicles in interstate commerce would result in 42 additional crashes each year. Here we address risk management issues by interpreting the number of additional crashes and the relative risks of the prospective handicapped drivers. Are the number of additional crashes (42) significant? Is the increase in the annual crash risk (from 0.00785 to 0.032 for non-insulin dependent and 0.048 for insulin dependent persons) significant? Are the relative risks significant for all insulin using drivers (4.7)? For drivers with a history of severe hypoglycemic reactions (19.8)? How should society tradeoff risk increases for increases in opportunity for these handicapped persons? We review other social decisions concerning highway safety: Accepting the increasing risks of letting 16 year olds drive, allowing extremely light cars, allowing some unsafe highways, and allowing extremely unsafe driving conditions at some times of day. We conclude that the additional risks from insulin using persons are well within the current accepted range of risks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341810 TI - Re-evaluation of the reference dose for methylmercury and assessment of current exposure levels. AB - Methylmercury (Me-Hg) is widely distributed through freshwater and saltwater food chains and human consumption of fish and shellfish has lead to widespread exposure. Both the U.S. EPA Reference Dose (0.3 micrograms/kg/day) and the FAO/WHO Permissible Tolerable Weekly Intake (3.3 micrograms/kg/week) are currently based on the prevention of paraesthesia in adult and older children. However, Me-Hg exposure in utero is known to result in a range of developmental neurologic effects including clinical CNS symptoms and delayed onset of walking. Based on a critical review of developmental toxicity data from human and animal studies, it is concluded that current guidelines for the prevention of paraesthesia are not adequate to address developmental effects. A dose of 0.07 micrograms/kg/day is suggested as the best estimate of a potential reference dose for developmental effects. Data on nationwide fish consumption rates and Me-Hg levels in fish/seafood weighted by proportion of the catch intended for human consumption are analyzed in a Monte Carlo simulation to derive a probability distribution of background Me-Hg exposure. While various uncertainties in the toxicologic and exposure data limit the precision with which health risk can be estimated, this analysis suggests that at current levels of Me-Hg exposure, a significant fraction of women of childbearing age have exposures above this suggested reference dose. PMID- 8341809 TI - An investigation of indoor air contamination in residences above dry cleaners. AB - An investigation of residences located above dry cleaning facilities was conducted to determine whether indoor and outdoor air concentrations of the dry cleaning solvent tetrachloroethene (perchloroethylene, PCE) were elevated compared to residences not near a dry cleaning facility. Data were also collected on the dry cleaners' operating conditions and equipment. Significantly elevated levels of PCE were found in the indoor air of each of six apartments located above dry cleaners compared to control residences for both day and night samples. The PCE concentrations in outdoor air near the dry cleaners were also significantly elevated compared to control locations and were lower than the concentrations measured indoors. The type of dry cleaning machine was significantly associated with the concentration of PCE found in the apartment above. A strong correlation was also found between the day and night PCE levels in the study apartments. PMID- 8341811 TI - [Serum ferritin and Still's disease in adults]. PMID- 8341812 TI - [Candidiasis in high-risk units. A pending problem]. PMID- 8341813 TI - [Candidiasis in an intensive care unit]. AB - The risk of being infected by candidiasis in an Intensive Care Unit (ICU) is evaluated, using an algorithm which allows the establishment of an early fungicidal treatment. This is a study which includes 34 patients with a mortality of 35%. Yeasts are detected from the second week at ICU, related with the long stay of patients at ICU and the relationship between mortality and age. The first positive sample usually does not indicate disseminate candidiasis (9%) or a positive blood culture (6%). Population defined as high risk for disseminated candidiasis (HRDC) with a negative blood culture has the worst prognosis (18 cases, 50% mortality rate). The six cases with HRDC with positive blood culture showed a mortality of 17%. In seven cases there were no HRDC criteria (mortality of 14%). With said study the existence or not of a HRDC could be determined, establishing the adequate antifungal treatment. PMID- 8341814 TI - [Disorders secondary to iodine deficiency in the autonomous community of the Murcia area]. AB - Hypothesis. To know goiter prevalence, iodine excretion and disorders associated to iodine deficiency in the region of Murcia, with the aim to define the need for establishing iodine prophylaxis programs. Method. Transversal study on 1956 pupils of the region of Murcia, with an age between four and seventeen years old, stratified by sex, age and area of origin, evaluating thyroid size, grade, weight, height, school performance and problems, menarche age, fish and iodine salt intake and iodine excretion. Results. Global prevalence of goiter was 29%, we found a mean ioduria of 93.92 +/- 56.83 micrograms/l. Anthropometric mean values for each age group did not differ between pupils affected by the lack of iodine and the others. A lower school performance was found in pupils with iodine deficit. Fish intake did not play a role in goiter prevalence. Conclusions. Murcia is an area affected by disorders derived from mild iodine deficiency, which implies the need to establish a continuous plan of effective prophylaxis with iodine salt. PMID- 8341815 TI - [Oxidative hepatic metabolism in chronic alcoholics during the acute abstinence period: evaluation with antipyrine elimination]. AB - In chronic alcoholics, while they consume ethanol, an increase in the oxidative hepatic metabolism is produced by means of an increment of microsomal enzymes induced by ethanol. In our study we have appraised this hepatic metabolism during the period of acute ethilic abstinence. This study has been performed in 20 chronic alcoholics without clinical symptoms, after five days free of ethanol drinks. The assessment of oxidative hepatic metabolism was realized by means of the measuring of corporal antipyrine clearance (by saliva elimination), being compared to those performed in a control group of ten healthy adults. Antipyrine clearance (5.5 +/- 2 l/h) is increased significatively in chronic alcoholics respect to the control group value (3.4 +/- 1 l/h) (p < 0.01). Elimination half life of antipyrine in chronic alcoholic groups (7.6 +/- 3 h) is decreased significatively respect to the control group value (11.2 +/- 2 h) (p < 0.01). During the period of acute abstinence, the oxidative hepatic metabolism persists increased. In these patients, when we administer drugs with hepatic metabolism following the same metabolic way that antipyrine, it will be necessary to readjust the maintenance dose to attain its therapeutic effect. PMID- 8341816 TI - [Paroxysmal dystonia as the first manifestation of multiple sclerosis]. AB - We discuss the case of a patient with episodes of left unilateral paroxysmal dystonia as first manifestation of multiple sclerosis, secondary to a demyelinization lesion in posterior arm of right internal capsule, detected by nuclear magnetic resonance (NMR). These episodes diminished with carbamazepine at low doses. PMID- 8341818 TI - [Epidermoid carcinoma of the pancreas associated with malignant humoral hypercalcemia]. AB - Pure squamous carcinoma is a rare pancreas cancer histological variety. Moreover the association of malign humoral hypercalcemia and neoplasia of the pancreas exocrine portion is extremely rare. The case of a patient with pure squamous pancreas carcinoma and hypercalcemia is discussed. The absence of bone metastasis allowed to classify it within the malign humoral hypercalcemia syndrome. It is the first case described in the spanish scientific literature and the third in the international literature of an epidermoid pancreas carcinoma associated to malign humoral hypercalcemia. PMID- 8341817 TI - [Usefulness of serology in the diagnosis of Candida tropicalis septicemia]. AB - In this study, we have evaluated the usefulness of eight serologic tests in the diagnosis of a Candida tropicalis septicaemia in a patient with acute myeloid leukaemia. Among the tests used, detection of mannose and candida antigen in serum allowed a high degree of suspicion of infection, earlier than the isolation of this species on mycological cultures from blood or oesophagic samples. Detection of anti-C. albicans antibodies was useless but low titres of anti-C. tropicalis antibodies were observed. In spite of early diagnosis and antifungal treatment, the complication of the disseminated candidiasis with a Pseudomonas aeruginosa septicaemia, concluded with the patient's exitus. PMID- 8341819 TI - [Intake of pollutants (heavy metals) via total diet at the national level as a whole and in autonomous communities: a new approach]. AB - As an answer to the request of information on the real intake of pollutants, both WHO and FAO recommend its study through the study of total diet. Following their criteria we have determined the contents of arsenic, cadmium, mercury and lead in the total mean spanish diet and in the seventeen Autonomous Regions, comparing them with the acceptable daily intakes (ADI). At the same time it is studied the contribution of the different groups of nutrients to the total pollutant charge. There is no detectable health risk due to the intake through the total diet of arsenic, mercury or lead. However the intake of cadmium from the total national reaches 85% of ADI, which is higher in Galicia (153%), Canary Islands (129%) and Cantabria (103%) and is very close in Murcia (97%), Asturias (92%) and the Balearic Islands (85%). PMID- 8341820 TI - [Gestational diabetes: new approaches to an old and growing problem]. AB - Gestational diabetes is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy. Gestational Diabetes generally disappears as soon as the pregnancy is terminated. The prevalence of gestational diabetes is 2% to 13%, depending on the genetic characteristics and environment of the population under study. Classic risk factors identify a population of women at risk of gestational diabetes (obesity, family history of diabetes, or previous poor obstetric history); however, these risk factors identify only 60% of women diagnosed as having gestational diabetes. Therefore, it is necessary to screen all pregnant women, regardless of history, for gestational diabetes. The optimal time to screen for gestational diabetes in pregnancy is between 24 and 28 weeks of gestation. The screening test consist of 50 g of oral glucose followed by a plasma determination at 1 hour. If the plasma glucose 1 hour after the oral load is > or = 140 mg/dl, a glucose tolerance test is indicated. The goal of management (diet, insulin and exercise) of the gestational diabetic women is to maintain normoglycemia, needed to avoid complications for the fetus and mother. PMID- 8341821 TI - [Current status of thrombolysis. The need for coadjuvant antithrombotic therapy]. AB - Thrombolytic therapy yields a 80% repermeabilitation in the acute myocardium infarct if applied soon. In other thrombotic sites such as deep venous thrombosis, pulmonary thromboembolism and peripheral arterial thrombosis, with no large cooperative randomized clinical trials, its usefulness is clear, tough selectively. The high rethrombosis frequency is the major drawback of this therapy. The concomitant use of an anti-thrombotic and/or anti-aggregant agent, even tough the possible higher risks of hemorrhages, seems a key element to improve the results obtained with thrombolysis. PMID- 8341822 TI - [Female with chronic lymphocytic leukemia with fast general deterioration, increase and fistulization of adenopathies and bone involvement]. PMID- 8341823 TI - [Supra-diaphragmatic primary amyloidosis diagnosed with oral biopsy]. PMID- 8341824 TI - [Round pneumonia and solitary nodule]. PMID- 8341825 TI - [Heart transplantation in Spain. The Official Report of the National Transplantation Organization on its activities in 1992]. PMID- 8341826 TI - [The usefulness of transesophageal echocardiography in assessing mechanical mitral prostheses. A comparison with transthoracic echocardiography]. AB - One hundred and sixty mechanical mitral prostheses were studied by transoesophageal echocardiography to ascertain the role of this technique in their functional assessment. All patients underwent transoesophageal echocardiogram, and, in 83, transthoracic Doppler-echocardiogram had already been performed immediately prior to transoesophageal echocardiogram. Prostheses presenting structural anomaly on bidimensional image and/or areas of regurgitation with predominantly turbulent flow on colour Doppler were considered to be dysfunctional. Of the 160 prostheses, 115 were considered normofunctional, and regurgitation was detected in 85 (94%) by transoesophageal echocardiogram and 10 (9%) by transthoracic echocardiogram; haemodynamic and/or surgical confirmation was obtained in 6 of these prostheses and all proved to be functioning normally. Of the 45 remaining prostheses considered to be dysfunctional, haemodynamic and/or surgical confirmation was obtained in 21 (the non-confirmed 24 were excluded from the study). Seventeen of the dysfunctional prostheses presented with areas of regurgitation of 3.9-24 cm2 (mean: 9.21 + 5.36); in one case, the degree of regurgitation with respect haemodynamic study was over-assessed; transthoracic echocardiogram detected only periprosthetic leaks in 38% of cases, with areas of regurgitation of 1.8-6.3 cm2 (mean: 1.87 + 2.02). The other 4 dysfunctional prostheses presented dysfunction due to thrombosis; all 4 were diagnosed by both transthoracic and transoesophageal echocardiogram. Transoesophageal echocardiogram detected 12 structural anomalies (1 vegetations, 4 thromboses and 7 dehiscencies), whereas transthoracic echocardiogram only detected these anomalies in five of the cases (1 vegetations and 4 thromboses). Transoesophageal echocardiography surpasses transthoracic echocardiography in the assessment of mechanical mitral prostheses and dysfunction diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341827 TI - [Transposition of the great arteries. Its anatomical correction. Our initial experience]. AB - Arterial switch correction of transposition of the great arteries has been performed without mortality on 8 children, 7 neonates and one 6 years old child, at our institution. One infant and the 6 year old child has previous pulmonary artery banding and modified Blalock-Taussig shunts. The coronary cuffs were anastomosed to the neo-aorta using the "trap-door" technique described by Mee and in seven the Lecompte manoeuvre was used. Postoperative management included treatment for persistent pulmonary hypertension and left ventricular dysfunction. All patients were discharged in satisfactory condition, and continue to do so at a maximum follow-up of ten months. These results encourage us to elect the arterial switch procedure as the primary treatment of transposition of the great arteries. PMID- 8341828 TI - [Transposition of the great arteries. Its arterial correction. The treatment of choice?]. PMID- 8341829 TI - [The development of the atrioventricular node and bundle of His in the human embryonic period]. AB - To study the development of the atrioventricular specific system, together with the closely related mesenchymal tissue (from which the fibrous skeleton of the heart later develops). Thirty human embryos ranging from 3 mm to 30 mm crown-rump length (Carnegie stages 10-23) were used. The primordium of the atrioventricular specific system was observed for the first time in human embryos of 10 mm Crown Rump length (Carnegie stage 16) as a cellular aggregate located below the inferior endocardial cushion. The primordium cells originate from the myocardium of the posterior wall of the atrioventricular canal. The primordium later forms both the atrioventricular node and the His bundle. The mesenchymal tissue which surrounds these features originates from the endocardial cushions (particularly from the inferior endocardial cushion). Todaro's tendon and the central fibrous body are later formed from the inferior endocardial cushion. The atrioventricular node and His bundle are both formed from the primordium of the atrioventricular specific system. The node is produced from the cranial-dorsal extension of the primordium while the His bundle is produced from the growth of the primordium in a ventral-caudal direction. The central fibrous body is anatomically defined in the stages post-dating morphogenesis of the atrioventricular specific system. PMID- 8341830 TI - [Transcatheter ablation with high-frequency currents as a method for creating useful experimental models in the study of cardiac conduction and automatism]. AB - PURPOSE: analyze the utility of transcatheter ablation with high-frequency currents to create different experimental models of altered cardiac automatism and conduction. METHOD: the results were obtained in six anesthetized dogs subjected to electrophysiological study after selectively applying transcatheter radiofrequency ablation to different zones of the specific cardiac conduction system. Ablation was carried out using conventional bipolar 7F catheter electrodes. High-frequency currents (0.7 MHz) were emitted through the distal electrode, with variable intensity and duration according to the aim of the experiment. Anatomic (fluoroscopic) and electrophysiological criteria were used to position the electrode within the ablation zone. RESULTS: selective radiofrequency application to the atrioventricular junction zone affords complete A-V blocks with escape rhythms located in the A-V node or His-Purkinje system, together with different degrees of infra- and intra-hisian and intranodal blocks. The modification of intranodal refractoriness and conduction without interrupting atrial pulse transmission may manifest atypical patterns with truncated nodal conduction curves. The abolition of sinus function through ablation in the zone of the sulcus terminalis makes it possible to obtain supraventricular subsidiary rhythms. The obtaining of intranodal complete blocks with supra-Hisian escape rhythms demonstrates phenomena such as the modulation of subsidiary automatism by non-transmitted atrial pulses, analyzed by constructing phase-response curves. CONCLUSION: transcatheter ablation using high-frequency currents is useful in demonstrating phenomena related to intranodal and His-Purkinje conduction, subsidiary pacemaker automatism or the modulation of automatism and conduction via non-transmitted pulses. PMID- 8341831 TI - [Cardiac arrhythmias (VII). Supraventricular tachycardias: the selection of the therapeutic options in the radiofrequency decade]. PMID- 8341832 TI - [The echocardiography of 10 cardiac myxomas with successful surgical treatment]. AB - Fifteen thousand patients were studied consecutively at the Echocardiographic Laboratory in the University Hospital Calixto Garcia. We found that one out of 1,500 patients studied (0.07%) presented a cardiac myxoma. Average age 40.8 years. Male sex was mainly (60%), and the interval between the onset of the symptoms and the diagnosis was 22.8 months. A previous diagnosis to Echo was performed in 30% of the patients despite of the recurrency and refractory therapeutics of symptoms. The echocardiographic data showed that left atrium and right ventricle dilatation were proportionally related to the tumor size and its mitral obstruction degree since 90% was localized at the left interatrial septum, and was presented at right ventricle septum and in both auricles in 2 patients. All the patients were successfully surgical treated and the 4-year Echo 2D study showed no tumoral recurrency. PMID- 8341833 TI - [The VVI pacemaker in the treatment of hypertrophic obstructive myocardiopathy in atrial fibrillation]. PMID- 8341834 TI - [Cerebral embolism as the first manifestation of Staphylococcus aureus endocarditis: the role of transesophageal echocardiography in the therapeutic decision]. AB - In patients with endocarditis due to Staphylococcus aureus, the issue of medical or surgical treatment still remains controversial. Likewise, there is no agreement in the management of those patients who have suffered cerebral embolism and show large vegetations in echocardiography. Moreover, transthoracic echocardiography not always disclose endocarditis vegetations as accurately as transesophageal echocardiography. We describe a patient with cerebral embolism due to Staphylococcus aureus endocarditis in which adequate medical diagnosis and management was achieved by means of transesophageal echocardiography. PMID- 8341835 TI - Observations on physical activity in physical locations: age, gender, ethnicity, and month effects. AB - The level of physical activity of 3- and 4-year-old children was assessed in alternative physical locations by month and time of day and by age, gender, and ethnicity. Physical activity was assessed by observation with the Children's Activity Rating Scale (CARS) for up to 12 hours from 7:00 am to 7:00 pm. A sample of 191 three- and four-year-old children was observed for up to four times in the course of a year. The sample was tri-ethnic. Boys were significantly more active than girls. Activity was consistently higher outside than inside. There were significant differences in the amount of time children in this age group spent inside versus outside by time of year; the activity levels of boys and girls differed by time of year, particularly when outside. A model including gender, month, and location terms accounted for 75% of the variance in physical activity. These data further documented gender differences in physical activity among very young children using measures not subject to self-report biases but did not explain or clarify the gender differences. The substantial differences by physical location and time of year deserve future attention, but more refined methods will be needed to balance data by location and important seasonal times. An inference from these results is that activity levels among young children may be increased by encouraging them to spend more time outdoors. PMID- 8341836 TI - The development of an instrument to measure motivation for marathon running: the Motivations of Marathoners Scales (MOMS). AB - This study reports the development of an instrument to assess the motives of marathon runners. The Motivations of Marathoners Scales (MOMS) contains 56 items distributed across nine scales. Content areas covered included health orientation, weight concern, self-esteem, life meaning, psychological coping, affiliation, recognition, competition, and personal goal achievement. Adequate internal consistency (Cronbach's alpha range .80 to .93), retest reliability (intraclass Rs range .71 to .90), and factorial validity of the scales were demonstrated. Assessment of the relationship between individual MOMS scales and other variables of conceptual relevance documents early evidence for the convergent and discriminant validity of the instrument. Future uses of the MOMS are discussed in light of theoretical, empirical, and practical considerations. PMID- 8341837 TI - Age and physical activity effects on reaction time and digit symbol substitution performance in cognitively active adults. AB - University professors (N = 56), divided into two age groups (< 50 years and > 50 years) and two physical activity level groups (high and low), were tested on three tasks requiring increasingly complex cognitive processing--simple reaction time (SRT), choice reaction time (CRT), and on a digit symbol substitution test (DSST). A significant main effect for exercise, with high active subjects performing better than low active subjects, was found for SRT (p < .001) and CRT (p < .01) but not for DSST (p < .09). Significant main effects for age, with younger subjects performing better than older subjects, were found on DSST (p < .01) and CRT (p < .05) but not for SRT (p < .09). The observation that the effect of age was more pronounced with increasing task complexity is consistent with previous research. However, the tendency for exercise effects to decrease with increasing task complexity is not consistent with former findings, suggesting that perhaps the controlled high level of cognitive activity of subjects in this study may have offset the usual effects of exercise on information processing speed. No significant Age x Activity Level interactions were found on any of the dependent raw score data. However, compared to normative scores of the population at large, there was a slight increase in DSST percentile ranks with age for the older aerobically active professors, whereas a decrease occurred for the inactive subjects. PMID- 8341838 TI - The influence of proficiency level, transfer distality, and gender on the contextual interference effect. AB - This study examined the impact of high and low proficiency level, transfer distality, and gender on the contextual interference effect with an open skill. Subjects were separated into two levels of proficiency based on performance on a pretest similar to the experimental task. Analysis of error scores during acquisition indicated that the partitioning of subjects according to ability level had been successful. Transfer distality was varied by presenting subjects with two tasks varying in similarity to the acquisition task. Analysis of absolute constant, constant, variable, and total error scores in transfer strongly suggested that subjects' consistency rather than response bias was affected by the experimental variables. The findings suggested that, for the task used in this study, proficiency level does not account for gender differences in the contextual interference effect, as the effect was only reliably found for females. For coincident timing skills, it appears that there may be two distinct conclusions drawn from the results of this study: contextual interference only benefits female subjects' consistency and the effect of contextual interference increases with the distality of transfer, regardless of the subjects' proficiency level. PMID- 8341839 TI - Players' perceptions of accountability factors in secondary school sports settings. AB - The purpose of this study was to gauge the extent to which students believed that the accountability strategies employed by their coaches had significant effects on their involvement in sports training sessions. Questionnaire data from 235 secondary school athletes were analyzed using linear structural relations to test a model of accountability hypothesized as operating in these coaching settings. The accountability strategy of active instruction was found to be a variable that significantly affected the students' valuing of their coaches as well as their task involvement. However, the rewards/consequences variable was not found to be a predictor of valuing or task involvement, suggesting that these athletes seemed more task oriented than reliant on external sanctions. The results of this study can only be generalized to team sport settings. Detailed examination needs to be made of the processes through which accountability factors operate for other contexts, including individual sports and competitive levels. Further research could also be undertaken into gender differences, especially in relation to the gender of coaches. PMID- 8341840 TI - Pedagogical knowledge structures in prospective teachers: relationships to performance in a teaching methodology course. AB - The purpose of the article is to describe the relationships of prospective teachers' pedagogical knowledge structures to performance in a physical education teaching methods class. The Pathfinder network scaling algorithm was used to elicit knowledge structures prior to and after the prospective teachers completed the class. The findings indicated that their knowledge of key pedagogical concepts was more coherent and corresponded more closely to the instructor's following the courses. Student measures of correspondence and coherence before the class were not significantly correlated with course performance; however, following the class, correlations between these measures and course performance were significant. Additionally, university grade point average (GPA) was highly related to course performance variables and knowledge measures, whereas American College Test (ACT) scores were not. A follow-up investigation of a subset of students indicated that key pedagogical concepts were retained over a 6-month period of time. However, performance on a semantic classification task provided little evidence that students with knowledge structures similar to that of the instructor organized knowledge at a more semantic level than students who were less similar. Future directions for the study of pedagogical knowledge acquisition in physical education are discussed. PMID- 8341841 TI - Effects of a curriculum and inservice program on the quantity and quality of elementary physical education classes. AB - The primary responsibility for engaging children in opportunities to be physically active and learn physical skills rests with school physical education. This study evaluated the effects of a combined health-related curriculum and inservice program on the quantity and quality of elementary school physical education lessons. Seven schools (N = 28 fourth-grade classes) in one district were randomly assigned to one of three conditions: 10 classes were taught in their usual manner by classroom teachers (Control [CO]); 10 classes were taught by trained classroom teachers (TT) who received inservice training and follow-up consultations; and 8 classes were taught by physical education specialists (PES) hired by the research project. Student activity level, curriculum context, and teacher behavior were directly observed and coded during a sample of 112 lessons over an 8-month period. Results indicated significant differences in both the frequency and mean length of classes (PES, 26.7 min; TT, 23.4 min; CO, 18.9 min). Additionally, the curriculum and inservice program equipped trained classroom teachers to provide significantly better classes than were provided by controls in terms of student activity engagement, lesson context, and active instructional behavior, though their classes did not match the quality of those taught by the physical education specialists. This study is unique in its use of direct observation of lessons to assess a curriculum and inservice intervention. PMID- 8341842 TI - A qualitative study on the socialization of beginning physical education teacher educators. AB - Few studies have focused on how university faculty learn and understand expectations of their professional role. The purpose of this study was to describe the experiences of five female physical education teacher educators in their first positions as assistant professors in research oriented universities. Data were collected using primarily qualitative methods--weekly journals and in depth interviews. Quantitative data were gathered to compare organizational factors such as salary, load allocation, equipment, and travel funds. Data yielded five main categories concerning how and what participants learned about their faculty roles. These categories included participants' perceptions of (a) organizational structure and job facilitation, (b) work tasks, (c) support systems, (d) evaluation and feedback, and (e) participants' psychological states. All participants reported experiencing role ambiguity and stress. Clear criteria for job performance, collegial support and mentoring, and regular evaluation and feedback were cited by all participants as important factors for reducing stress and facilitating their roles as faculty. PMID- 8341843 TI - Aerobic capacity in black adolescent girls. AB - Our purpose was to determine the aerobic capacities (VO2max) of a group of black female adolescents (age = 11.4-15.8 years) randomly chosen from a single urban school. Of 91 girls selected, 64 performed an incremental treadmill running test to volitional exhaustion and achieved VO2max as determined from expired gas measures. Other measures included height (m), weight (kg), and calf and triceps skinfolds (for % fat estimates). Girls were also asked whether they had achieved menarche. VO2max averaged 37.3 +/- 6.2 ml.kg-1 x min-1 and was significantly correlated (r[62]) with height (-.32, p < .01), body mass index (-.63, p < .001), and % fat (-.65, p < .001) but not with age (-.16, p > .10). Postmenarchal girls were significantly taller and older than premenarchal girls. Contrary to previous studies, the girls' VO2max values were not related to biological age. Our subjects' aerobic capacity values averaged 14% less than those of nonblack U.S. female adolescents previously reported in the literature. This difference in VO2max was primarily a function of body weight. Study implications support the possibility that overweight in adult black women may originate prior to or during early adolescence. Future longitudinal studies should be designed to investigate the effects of aerobic fitness on cardiovascular risk factor reduction in black adolescent girls. PMID- 8341844 TI - The effects of conceptually based physical education programs on attitudes and exercise habits of college alumni after 2 to 11 years of follow-up. PMID- 8341845 TI - Graphic versus numeric knowledge of results: which mode? PMID- 8341846 TI - More on assessing the retention of motor learning based on restricted information. PMID- 8341847 TI - Determination of the aerobic benefit of selected physical education activities. PMID- 8341848 TI - The effects of experience on the detection and location of performance differences in a gymnastic technique. PMID- 8341849 TI - The effects of variable practice on the performance of a basketball skill. PMID- 8341850 TI - The incidence of bulimia nervosa and pathogenic weight control behaviors in female collegiate gymnasts. PMID- 8341851 TI - Predicting the presence of pulmonary function impairment in adult respiratory distress syndrome survivors. AB - Varying degrees of impairment in pulmonary function in survivors of adult respiratory distress syndrome (ARDS) have been reported. Physiologic indices of the severity of disease have been associated with impaired pulmonary function after ARDS, including duration of exposure to FIO2 > 0.6, AaDO2, maximal mean pulmonary artery pressure, lowest total static thoracic compliance, and peak airway pressure. Prediction of impairment following ARDS is difficult because clinical observations may reflect reversible lung injury (e.g. lung edema) and clinical features of ARDS do not predict subsequent function reliably. We developed a severity score to predict the presence of impairment of pulmonary function in 51 ARDS survivors, by examining the following clinical variables: (1) predisposing factor for ARDS; (2) age; (3) sex; (4) severity of hypoxemia; (5) smoking history; (6) number of days of positive pressure ventilation; (7) lowest total static thoracic compliance; (8) maximal mean pulmonary artery pressure, and (9) presence of barotrauma. Pulmonary function studies were performed at least 1 year after ARDS onset. The ARDSscore developed required only two variables: ARDSscorce = duration of positive pressure ventilation (days) minus lowest static thoracic compliance (ml/cm H2O). Significant correlations (p < 0.001) were found between linear regressions of percent predicted FEV1, FVC, TLC and DLCO against ARDSscore. ARDSscore > +20 predicted an 82% probability of impaired FEV1, FVC or TLC and a 100% probability of an impaired DLCO. We conclude that a score based upon duration of positive pressure ventilation and lowest static thoracic compliance predicts impaired pulmonary function more than 1 year after ARDS. PMID- 8341852 TI - Bronchiolitis obliterans after bone marrow transplantation: the effect of preconditioning. AB - While half of all patients receiving bone marrow transplantation (BMT) for malignancies and related diseases may achieve prolonged disease-free survival, 2 10% of patients undergoing allogeneic transplantation develop bronchiolitis obliterans (BrOb). We have hypothesized that total body irradiation (TBI) which has been used for pretreatment may influence the subsequent development of BrOb in patients undergoing allogeneic BMT. Since 1976, we have treated 104 patients undergoing allogeneic BMT with non-TBI preconditioning. Of 60 patients that survived and were evaluable for chronic graft versus host disease (GVHD) 26 developed chronic GVHD (43%). Four of 104 patients (3.9%) developed BrOb by clinical and/or pathologic findings. Four of 4 patients (100%) with BrOb had chronic GVHD. Two of these 4 patients (50%) were alive at the end of 2 years. These data demonstrate that chronic GVHD is a risk factor for BrOb in patients receiving non-TBI preconditioning regimens. The similar incidence of BrOb in this population compared to other studies using TBI suggest that the preconditioning regimen is not a factor in the development of BrOb. Further study is needed to confirm these findings. Allogeneic bone marrow transplantation (BMT) has revolutionized the therapeutic approach toward acute and chronic leukemias, aplastic anemia and rare immunodeficiency disorders. Half of all patients that undergo BMT achieve long-term disease-free survival but a similar number develop significant complications [1].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341853 TI - Pulmonary manifestations in adult T-cell leukemia at the time of diagnosis. AB - Adult T-cell leukemia (ATL) is an underlying immunodeficient condition which often leads to various kinds of pulmonary diseases. We have analyzed 35 consecutive patients (18 male, 17 female) with ATL to see to what extent pulmonary complications were involved at the time of diagnosis. Over one-third presented with respiratory symptoms and 14 (40%) patients had significant findings on chest radiographs on the first admission in which reticulo-nodular shadows were predominant in 10 patients, suggesting that overt ATL is preceded by interstitial pulmonary disease. In addition, bacterial pneumonia and pneumocystosis were experienced in over two-thirds of the patients during the clinical course, and more than half of the patients subsequently died of pulmonary complications suggesting that early institution of diagnostic procedures and treatment for pulmonary conditions is needed in ATL patients. PMID- 8341854 TI - Diffuse interstitial fibrosis in nonasbestos pneumoconiosis--a pathological study. AB - Pathological examinations of 233 consecutive autopsy cases with nonasbestos pneumonconiosis revealed evidence of diffuse interstitial fibrosis (DIF) in 64 (27.5%), among whom 45 (19.3%) showed bilateral involvement and 9 (3.9%) extensive disease closely resembling usual interstitial pneumonia. The patients with DIF were significantly older and had longer occupational histories as compared with those without DIF. There was no correlation between the occurrence of DIF and the type of the underlying disease (silicosis or mixed dust pneumoconiosis) except that an extensive DIF was more frequently associated with mixed dust pneumoconiosis. The extensive DIF developed an in situ malignancy much more frequently (33.3%) than the focal disease (2.6%). PMID- 8341855 TI - Obstructive sleep apnea in the Rubinstein-Taybi syndrome. AB - The Rubinstein-Taybi syndrome is characterized by a pattern of malformations including broad thumbs and big toes, microcephaly, facial dysmorphism, small stature, and mental retardation. Obstructive sleep apnea (OSA), has been described in several facial or skeletal malformations, but never in the Rubinstein-Taybi syndrome. We studied a 9-year-old boy, previously diagnosed as having the Rubinstein-Taybi syndrome and affected by severe OSA, as documented by polysomnography. He manifested the habitual and heavy snoring with breathing difficulties at night, and excessive daytime sleepiness. Short neck and obesity were important factors for the severity of the syndrome. Continuous positive airway pressure was not tolerated and weight loss was the only possible treatment, as upper airway surgery was not indicated by cephalometric, otolaryngologic or clinical results. PMID- 8341856 TI - Sarcoid reactions in regional lymph nodes of primary lung cancer. AB - A 66-year-old woman diagnosed as having primary lung cancer with an enlargement of the mediastinal, subcarinal and bilateral hilar lymph nodes underwent a thoracotomy after preoperative chemotherapy. The histological examination showed a moderately differentiated papillary adenocarcinoma in the left upper lobe without any metastases to the regional lymph nodes; however, non-caseous epithelioid granulomas without necrosis were observed in the nodes. These changes were considered to be sarcoid reactions, since no other physiological and laboratory findings compatible with systemic sarcoidosis were observed. The histological findings suggested the possibility that the regional lymph nodes were not involved with the tumor cells at the time of lung cancer diagnosis. Despite the rarity of this condition, sarcoid reactions in the regional lymph nodes must be kept in mind when an enlargement of bilateral hilar lymph nodes is detected in patients with lung cancer, and a good prognosis may be expected in cases with sarcoid reactions in the regional lymph nodes. PMID- 8341857 TI - Two-dimensional echocardiographic assessment of right cardiac pressure overload in patients with chronic obstructive airway disease. AB - Two-dimensional echocardiography was used to estimate right cardiac pressure overload in patients with chronic obstructive airway disease. Area measurements of the four heart chambers were carried out from the apical four-chamber view. Additionally, the respiratory behaviour of the inferior vena cava was examined from the subcostal view. A good apical imaging of the four-chamber view for area measurement was obtained in 44 out of 48 patients with chronic obstructive airway disease. The respiratory behaviour of the inferior vena cava was investigated from the subcostal view in 38 patients. Within 8 days after echocardiography, right cardiac catheterization was carried out in order to measure pulmonary artery and right atrial mean pressures and to determine pulmonary vascular resistance. A good correlation was found between pulmonary artery mean pressure and the following echocardiographic parameters: area index (area/body surface) of the two right heart cavities (r = 0.83), right-to-left ventricular area ratio (r = 0.82) and right-to-left cardiac area ratio (ratio between the added areas of both right heart cavities on the one side and the added areas of both left heart cavities on the other; r = 0.82). Correlation between these parameters and pulmonary vascular resistance (r = 0.71, 0.66 and 0.71, respectively) and between the right atrial mean pressure and the right atrial area index was less close (r = 0.64). On the other hand, the respiratory behaviour of the inferior vena cava proved to be highly specific but not very sensitive in predicting a pathological right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341858 TI - Atrial natriuretic peptide and bronchial hyperresponsiveness in patients with mitral stenosis. AB - Atrial natriuretic peptide (ANP) has been reported to have protective effects against methacholine-induced bronchoconstriction in asthmatics. The aim of the study was to evaluate the relationship between plasma ANP levels and bronchial responsiveness to methacholine in patients with mitral stenosis. In 12 patients with moderate mitral stenosis, age 35-58 years, 9 female, 8 in NYHA class 2, 4 in NYHA class 3 for symptoms, plasma ANP and bronchial threshold to methacholine (PD20FEV1) were determined. The same measurements were performed in 10 asthmatic patients, hyperresponsive to methacholine, and in 10 normal subjects, nonresponsive to methacholine. Mean +/- SE plasma ANP levels were significantly higher in patients with mitral stenosis in comparison with asthmatics and normals (159 +/- 41.8, 7.3 +/- 0.98, 7.6 +/- 1.3, respectively, p < 0.01). In patients with mitral stenosis there was a significant relationship between plasma ANP and PD20FEV1 (r = 0.81, p < 0.01). No relationship was found between ANP and PD20FEV1 in asthmatics. In conclusion, in patients with mitral stenosis ANP seems to play a protective role against bronchial hyperresponsiveness to methacholine. PMID- 8341860 TI - Increased endothelin-like immunoreactive material on bronchoalveolar lavage fluid from patients with bronchial asthma and patients with interstitial lung disease. AB - Endothelin (ET) is an endothelial regulatory peptide present also in pulmonary tissue where it exerts several biological actions both on bronchial and vascular smooth muscle cells. It has been shown to increase in bronchoalveolar lavage fluid (BALF) from asthmatic patients; but changes in other chronic respiratory disease have not been well studied. We measured by a radioimmunoassay (RIA) ET immunoreactive (IR) levels on BALF (BALF-ETIR, pg/ml) from 5 normal subjects (NS), 5 patients with chronic extrapulmonary disease (ED) without signs of lung involvement, 5 patients with allergic bronchial asthma (BA), 10 patients with idiopathic lung fibrosis (ILF) and 9 patients with miscellaneous interstitial lung disease (MILD). In 5/5 NS and 4/5 ED BALF-ETIR was lower than sensibility of RIA test used (0.8 pg/ml). BALF-ETIR was dosable in all patients with bronchopulmonary disease; means were 2.45 pg/ml in BA, 12.37 pg/ml in ILF, 2.90 pg/ml in MILD--Wilcoxon's rank test (two tailed) versus NS, p < 0.05. There was an inverse correlation between BALF-ETIR values and the degree of ventilatory impairment (forced vital capacity % of predicted value, r = -0.61 p < 0.01; forced expiratory volume in 1 s % of predicted value, r = -0.71 p < 0.01) and the level of arterial pressure of O2 (PaO2; r = -0.75 p < 0.01); a positive correlation was found with number of neutrophils/ml of BALF (r = 0.52 p < 0.01)- Spearman's rank correlation. Though rarely detected on BALF from normal lungs, ET increases on BALF in patients with bronchopulmonary disease, raising the question of its involvement in pathogenic mechanisms or evolution of bronchial asthma and interstitial lung disease. PMID- 8341859 TI - Comparison of bronchodilator effects of fenoterol/ipratropium bromide and salbutamol in patients with chronic obstructive lung disease. AB - A double-blind, randomized cross-over trial was carried out in 24 patients with chronic airflow obstruction. The patients were required to demonstrate a minimum 15% absolute increase in forced expiratory volume (FEV1) after a standard dose (0.4 mg) of fenoterol (F). On a separate occasion the effect of ipratropium bromide (IB; 0.04 mg) on FEV1 was tested also; according to the increase in FEV1 the patients were grouped into IB responders (delta FEV1 > 15%) and IB nonresponders (delta FEV1 < 15%). Two puffs of F/IB (0.1 mg/0.04 mg), salbutamol (S; 0.2 mg) and placebo (P) were given by metered-dose inhaler at the same time of the day on three different occasions. FEV1 and specific airway resistance (sRaw) were assessed before and at specific intervals following inhalation. The results showed that F/IB and S produced similar maximal increases in FEV1 (delta FEV1 32% for F/IB and 31% for S) and decreases in sRaw (delta sRaw 24% for F/IB and 21% for S). These effects were significantly different both from baseline values and from P. FEV1 was still significantly different 8 h after inhalation from P in the F/IB group, but not in the group that received S. The effect of IB on FEV1 in the pretest was compared with the subsequent response to F/IB. In IB responders F/IB seemed to produce slightly more effective bronchodilation. Side effects were minimal and clinically insignificant. In conclusion, F/IB, with its ability to effect sustained bronchodilation without adverse side effects, is a viable alternative to a monotherapy in chronic obstructive pulmonary disease. PMID- 8341861 TI - Psychosocial changes in patients participating in a chronic obstructive pulmonary disease rehabilitation program. AB - Changes in physical competence, respiratory symptoms, well-being, emotional state, level of depression, every-day coping skills, and general activity and independence were studied in 40 chronic obstructive pulmonary disease patients participating in an intensive 3-week rehabilitation program. Both patient and staff ratings were used. Expectations and attitudes prior to rehabilitation were also measured. The study design included a 3-week basal period, a 3-week rehabilitation period and a 6-month follow-up. The immediate effects of rehabilitation on the variables which described subjective experiences were positive: well-being, emotional state and respiratory symptoms improved significantly (p < 0.001, p < 0.01 and p < 0.01, respectively). By the end of the follow-up period, however, all the treatment effects had dissipated. No significant effects of rehabilitation could be seen in every-day coping skills, general activity and independence or level of depression. It was not possible to predict the rehabilitation response on the basis of the patients' attitudes, expectations, level of depression or age. We conclude that pulmonary rehabilitation causes transient improvement in respiratory symptoms and some subjectively characterized psychosocial variables and that this improvement is unpredictable by attitude and expectation variables. PMID- 8341862 TI - Reducing attrition bias with an instrumental variable in a regression model: results from a panel of rheumatoid arthritis patients. AB - This study proposes an econometric technique to reduce attrition bias in panel data. In the simplest case, one estimates two regressions. The first is a probit regression based on sociodemographic and clinical characteristics measured at baseline. The probit regression estimates the probability that subjects stay or leave over the duration of the study. We insert the predicted probabilities from the probit regression into an inverse Mills ratio (IMR) or hazard rate to form an instrumental variable. We use this instrumental variable subsequently as an additional covariate in a second regression model that attempts to explain fluctuations in the dependent variable. The second regression, which is linear, includes only subjects who remained in the study. In alternative models, instrumental variables are created using predicted values from least squares and logit regressions estimating the probability that subjects stay or leave. The use of the instrumental variables reduces the effects of attrition bias in the linear regression model. We applied the technique to a panel of patients with rheumatoid arthritis (RA) enrolled in 1981 and followed through 1990. We attempted to predict values for a measure of functional disability recorded in 1990 with use of covariates measured in 1981. The dependent variable was an index of disability in 1990 and the independent variables (covariates) included the disability index from 1981, the years of duration of RA, gender, marital status, education, and age in 1981. The correction technique suggested that ignoring attrition bias would underestimate the strength of associations between being female and the subsequent disability index, and overestimate the strength of associations between being married spouse present, age, and the initial disability index on the one hand and the subsequent disability index on the other. PMID- 8341863 TI - Robust inference for multivariate survival data. AB - Multivariate survival data arise when an individual records multiple survival events or when individuals recording single survival events are grouped into clusters. In this paper we propose a new method for the analysis of multivariate survival data. The technique is a synthesis of the Poisson regression formulation for univariate censored survival analysis and the generalized estimating equation approach for obtaining valid variance estimates for generalized linear models in the presence of clustering. When the survival data are clustered, combining the methods provides not only valid estimates for the variances of regression parameters but also estimates of the dependence between survival times. The approach entails specifying parametric models for the marginal hazards and a dependence structure, but does not require specification of the joint multivariate survival distribution. Properties of the methodology are investigated by simulation and through an illustrative example. PMID- 8341864 TI - Tests for qualitative treatment-by-centre interaction using a 'pushback' procedure. AB - In multicentre clinical trials using a common protocol, the centres are usually regarded as being a fixed factor, thus allowing any treatment-by-centre interaction to be omitted from the error term for the effect of treatment. However, we feel it necessary to use the treatment-by-centre interaction as the error term if there is substantial evidence that the interaction with centres is qualitative instead of quantitative. To make allowance for the estimated uncertainties of the centre means, we propose choosing a reference value (for example, the median of the ordered array of centre means) and converting the individual centre results into standardized deviations from the reference value. The deviations are then reordered, and the results 'pushed back' by amounts appropriate for the corresponding order statistics in a sample from the relevant distribution. The pushed-back standardized deviations are then restored to the original scale. The appearance of opposite signs among the destandardized values for the various centres is then taken as 'substantial evidence' of qualitative interaction. Procedures are presented using, in any combination: (i) Gaussian, or Student's t-distribution; (ii) order-statistic medians or outward 90 per cent points of the corresponding order statistic distributions; (iii) pooling or grouping and pooling the internally estimated standard deviations of the centre means. The use of the least conservative combination--Student's t, outward 90 per cent points, grouping and pooling--is recommended. PMID- 8341865 TI - Evaluation of multicentre clinical trial data using adaptations of the Mosteller Tukey procedure. AB - Two procedures, based on proposals discussed by Mosteller and Tukey, are described for obtaining a combined estimate of the difference between two treatment means and its confidence interval from multicentre clinical trial data. Both procedures provide estimates in the possible presence of heteroscedasticity. The first procedure is designated the primary analysis for efficacy assessment. It omits treatment-by-centre interaction from the error term for treatment, unless there is substantial evidence of qualitative interaction (Ciminera et al.) or other special circumstances. The second procedure is the primary analysis whenever there is substantial evidence of qualitative interaction, and can be used whenever there are other reasons to make an analysis allowing for interaction. PMID- 8341866 TI - Calculation of power and sample size with bounded outcome scores. AB - The two-sample Wilcoxon rank sum test is the most popular non-parametric test for the comparison of two samples when the underlying distributions are not normal. Although the underlying distributions need not be known in detail to calculate the null distribution of the test statistic, parametric assumptions are often made to determine the power of the test or the sample size. We encountered difficulties with this approach in the planning of a recent clinical trial in stroke patients. It is shown that, for power and sample size estimation, it can be dangerous to apply the classical formulae routinely, especially with outcome scores having a U-shaped or a J-shaped distribution. As an example we have taken the Barthel index, a quality-of-life outcome measure in stroke patients. Further, we have investigated alternative methods by means of Monte Carlo simulation. The distributional characteristics of the estimated powers were compared. Our findings suggest more appropriate computer software is necessary for the calculation of power and sample size when efficacy is measured by a non parametric method. PMID- 8341867 TI - Sample size determinations using logistic regression with pilot data. AB - Suppose the goal of a projected study is to estimate accurately the value of a 'prediction' proportion p that is specific to a given set of covariates. Available pilot data show that (1) the covariates are influential in determining the value of p and (2) their relationship to p can be modelled as a logistic regression. A sample size justification for the projected study can be based on the logistic model; the resulting sample sizes not only are more reasonable than the usual binomial sample size values from a scientific standpoint (since they are based on a model that is more realistic), but also give smaller prediction standard errors than the binomial approach with the same sample size. In appropriate situations, the logistic-based sample sizes could make the difference between a feasible proposal and an unfeasible, binomial-based proposal. An example using pilot study data of dental radiographs demonstrates the methods. PMID- 8341868 TI - International Collaborative Group on Clinical Trial Registries (ICG-CTR) consensus recommendations. PMID- 8341869 TI - A comparison of different matching designs in case-control studies: an empirical example using continuous exposures, continuous confounders and incidence of myocardial infarction. AB - The paper presents a case-control study involving a disease, exposures and several continuous confounders. The relative efficiency and validity of a fully matched design is compared with random sampling of controls. We test a viable option of a partially matched design when inability to match all study subjects on all confounders occurs. The degree of bias in the odds ratios introduced by the different designs and by the different analytic models is assessed in comparison with the estimates obtained from a total cohort, from which both cases and controls were selected. Matched designs and analytic strategies are also evaluated in terms of the variances of the odds ratios. The results indicate that matching on continuous variables may lead to a more precise estimate of odds ratio than statistical control of confounding in unmatched designs. Partial selection of controls by matching may be a useful strategy when complete matching cannot be achieved; in practice, partial matching achieves most of the benefits of full matching. PMID- 8341871 TI - Physical allergies and exercise. Clinical implications for those engaged in sports activities. AB - There are several allergic responses that may occur in susceptible individuals as a result of exposure to physical stimuli. Most of these conditions are mediated by vasoactive substances and usually result in symptoms of urticaria and/or angioedema. There are 2 such conditions that may occur as a direct result from exercise. The first of these is cholinergic urticaria. Patients with cholinergic urticaria experience punctate (2 to 4mm) hives which occur reproducibly with exercise or with passive warming, such as might occur in a steam bath or hot pool. Life-threatening hypotension or angioedema usually do not occur with cholinergic urticaria. This condition usually responds well to oral hydroxyzine. Exercise-induced anaphylaxis (EIA) is a form of physical allergy that has been recognised with increasing frequency in recent years. This syndrome typically presents with generalised pruritus, a flushing sensation, a feeling of warmth and the development of conventional (10 to 15mm) urticaria in association with vigorous physical exertion only. Symptoms tend to occur variably with exposure to exercise and do not typically occur with passive warming. During symptomatic attacks, cutaneous mast cells degranulate and serum histamine levels increase. Treatment is problematic. Cessation of exercise with onset of symptoms and self administration of epinephrine (adrenaline) are recommended. Other physical allergies that may affect exercising individuals include cold urticaria, localised heat urticaria, symptomatic dermatographism (dermographism), delayed pressure urticaria (angioedema), solar urticaria and aquagenic urticaria. Management of these conditions may include patient education, selective avoidance, antihistamines and, in some cases, induction of tolerance. PMID- 8341870 TI - Physical activity in older adults. An overview of health benefits. PMID- 8341873 TI - Resistance training during preadolescence. Issues and controversies. AB - High intensity resistance training appears to be effective in increasing strength in preadolescents. Children make similar relative (percentage improvement), but smaller absolute, strength gains compared with adolescents and young adults in response to similar resistance training programmes. Resistance training appears to have little if any effect on muscle size, and strength gains during training have been associated with increases in levels of neuromuscular activation and changes in intrinsic contractile characteristics of muscle. Although unsubstantiated, improved motor coordination probably also contributes to the increase in strength, especially for more complex strength manoeuvres. On the basis of limited information, training-induced strength gains are lost during detraining, and the decay in strength has been associated with a reduction in neuromuscular activation. Short term resistance training appears to have no effect on somatic growth (height or weight) and body composition, and no proven positive influence on sports performance, injury rate or recovery from injury during preadolescence. Weightlifting has proved injurious to some children, especially when unsupervised and without instruction in proper weightlifting technique and load selection. In contrast, the risk of injury from prudently prescribed and closely supervised resistance training appears to be low during preadolescence. Lastly, short term resistance training appears to have no detrimental effect during preadolescence on either cardiorespiratory fitness or resting blood pressure. PMID- 8341875 TI - [Role of the radiologist in the resection of suspect, non-palpable breast lesions]. PMID- 8341874 TI - Current concepts in the treatment of common compartment syndromes in athletes. AB - Compartment syndromes of the leg, and to a lesser extent the forearm and other areas, occur in both acute and chronic exertional forms. Similar inciting events may precipitate either form, with different presentations, prognoses and implications for treatment. A complete knowledge of the anatomy and pathophysiology of these syndromes is essential for diagnosis. Measurement of compartment pressures is a valuable tool in the diagnosis of chronic exertional compartment syndrome. In our experience, athletes who desire to return to the same level of exercise will require fascial release, although symptoms may improve if the intensity or duration of the activity is decreased. Fascial release is the treatment of choice in acute compartment syndrome and in chronic exertional compartment syndrome unresponsive to nonoperative treatment. PMID- 8341872 TI - Velocity specificity of resistance training. AB - Velocity specificity of resistance training has demonstrated that the greatest strength gains occur at or near the training velocity. There is also evidence that the intent to make a high speed contraction may be the most crucial factor in velocity specificity. The mechanisms underlying the velocity-specific training effect may reside in both neural and muscular components. Muscular adaptations such as hypertrophy may inhibit high velocity strength adaptations due to changes in muscle architecture. However, some studies have reported velocity-specific contractile property adaptations suggesting changes in muscle kinetics. There is evidence to suggest velocity-specific electromyographic (EMG) adaptations with explosive jump training. Other researchers have hypothesised neural adaptations because of a lack of electrically evoked changes in relation to significant voluntary improvements. These neural adaptations may include the selective activation of motor units and/or muscles, especially with high velocity alternating contractions. Although the incidence of motor unit synchronisation increases with training, its contribution to velocity-specific strength gains is unclear. However, increased synchronisation may occur more frequently with the premovement silent period before ballistic contractions. The preprogrammed neural circuitry of ballistic contractions suggests that high velocity training adaptations may involve significant neural adaptations. The unique firing frequency associated with ballistic contractions would suggest possible adaptations in the frequency of motor unit discharge. Although co-contraction of antagonists increases with training and high velocity movement, its contribution is probably related more to joint protection than the velocity-specific training effect. PMID- 8341876 TI - [The role of ultrasonography in non-palpable lesions of the breast]. PMID- 8341877 TI - [Non-palpable lesions of the breast: biopsy techniques]. PMID- 8341878 TI - [Perioperative risk: evaluation methods]. PMID- 8341879 TI - [Celioscopy and abdominal surgery of adnexitis]. PMID- 8341880 TI - [Review of methotrexate treatment of persistent extrauterine pregnancy]. PMID- 8341881 TI - [Vaginal hysterectomy assisted by laparoscopy--experiences in Vaud]. PMID- 8341882 TI - [Contribution of nuclear magnetic resonance imaging in the diagnosis and pathogenesis of brain stem and cerebellar infarction]. PMID- 8341883 TI - [Contribution of magnetic resonance to the diagnosis of multiple sclerosis]. PMID- 8341885 TI - [Pulmonary opacity in a 47-year-old crane operator]. PMID- 8341884 TI - [Allergic asthma and environment--effect of atmospheric pollution]. PMID- 8341886 TI - [Homage to Professor Julian de Ajuriaguerra]. PMID- 8341887 TI - [Trauma pathology of the wrist in the general practitioner's office]. PMID- 8341888 TI - [The pulverisator of Just Lucas-Champonniere, according to Lister (1876)]. PMID- 8341889 TI - [The drug addict: the ideal consumer, the most accomplished.... Apropos of Jean Martin's article]. PMID- 8341890 TI - Sedative effects and plasma concentrations following single doses of triazolam, diphenhydramine, ethanol and placebo. AB - Twelve, healthy, young men received 0.25 mg triazolam and ethanol placebo, 50 mg diphenhydramine and ethanol placebo, 0.6 g/kg ethanol and placebo pill and ethanol placebo and placebo pill in a double-blind Latin Square design. Each of the four treatments were administered for 2 days at 0900 hours with blood samples drawn on day one at 0830, 1030, 1230, 1430 and 1630 hours, and sleep latency and performance assessed on day two at 1000, 1200, 1400 and 1600 hours. Significant sedative effects of ethanol, triazolam and diphenhydramine relative to placebo were observed on the sleep latency and performance measures with the effects being detected over the full 6.5 hours of assessment. Among the active drugs, triazolam and diphenhydramine had similar sedative effects which differed from that of ethanol. Plasma concentration of each drug declined significantly over the 6.5 hours. Ethanol reached zero, but triazolam and diphenhydramine did not. Continued sedation (sedative effects after plasma concentration reached zero) was observed with ethanol. PMID- 8341891 TI - Treatment of narcolepsy with methamphetamine. AB - Eight pairs of subjects (each consisting of a narcoleptic and a control matched on the basis of age, sex, educational background and job) were evaluated under the following double-blind, randomized treatment conditions: baseline, placebo, low dose and high dose methamphetamine. Subjects were drug-free for 2 weeks prior to beginning the protocol. Methamphetamine was the only drug taken during the protocol and was given in a single morning dose of 0, 20 or 40-60 mg to narcoleptics and 0, 5 or 10 mg to controls. The protocol was 28 days long, with each of the four treatment conditions lasting 4 days followed by 3 days of washout. Nighttime polysomnography and daytime testing were done during the last 24 hours of each treatment condition. Daytime sleep tendency was assessed with the multiple sleep latency test (MSLT). Daytime performance was assessed with performance tests including a simple, computer-based driving task. Narcoleptics' mean MSLT sleep latency increased from 4.3 minutes on placebo to 9.3 minutes on high dose, compared with an increase from 10.4 to 17.1 minutes for controls. Narcoleptics' error rate on the driving task decreased from 2.53% on placebo to 0.33% on high dose, compared with a decrease from 0.22% to 0.16% for controls. The effects of methamphetamine on nocturnal sleep were generally dose-dependent and affected sleep continuity and rapid eye movement (REM) sleep. Elimination half life was estimated to be between 15.9 and 22.0 hours. Mild side effects emerged in a dose-dependent fashion and most often involved the central nervous system and gastrointestinal tract. We concluded that methamphetamine caused a dose-dependent decrease in daytime sleep tendency and improvement in performance in both narcoleptics and controls. Methamphetamine at doses of 40-60 mg allowed narcoleptics to function at levels comparable to those of unmedicated controls. PMID- 8341892 TI - Effects of zolpidem and triazolam on sleep and respiration in mild to moderate chronic obstructive pulmonary disease. AB - Sleep problems and nocturnal arterial oxygen desaturation are common in patients with chronic obstructive pulmonary disease (COPD). Hence, the safety and efficacy of new hypnotic agents must be ascertained in this group of patients. We performed a double-blind, randomized, single-dose, placebo and active drug controlled, crossover study in 24 patients with insomnia (subjective sleep latency > 30 minutes and sleep duration 4-6 hours) and mild to moderate COPD (mean FEV1 61 +/- 12(SD)% predicted) in order to establish the effects of zolpidem 5 mg and 10 mg on sleep and respiration and to compare these effects with triazolam 0.25 mg. Arterial oxygen saturation for the entire night, by hour and stage, and the apnea-hypopnea index for the entire night were not significantly different with placebo and the various drug conditions. Total sleep time and sleep efficiency were increased over placebo by all three drug conditions. Triazolam was more effective than zolpidem 5 mg but not zolpidem 10 mg, and there was no significant difference between zolpidem 5 mg and zolpidem 10 mg. Zolpidem 10 mg and triazolam both reduced the number of awakenings (> 15 seconds duration) per hour of sleep. Although there was a trend for triazolam to be more efficacious than zolpidem 10 mg, no statistically significant difference was found for any objective or subjective sleep variable. Likewise, zolpidem 10 mg tended to be more efficacious than zolpidem 5 mg, but the difference was only significant in terms of perceived sleep quality and ease of falling asleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341893 TI - Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. AB - In a double-blind randomized crossover trial, oxycodone or placebo was given in divided night-time doses to 11 patients with idiopathic restless legs syndrome (RLS) for 2 weeks prior to appropriate polysomnographic studies. Under double blinded conditions, patients were asked to do daily ratings of their leg sensations, motor restlessness and daytime alertness on a 1-4 scale for the 2 weeks prior to the polysomnographic studies and for the nights of the polysomnographic studies as well. Leg sensations (p < 0.009), motor restlessness (p < 0.006) and daytime alertness (p < 0.03) were significantly improved on oxycodone as compared to baseline or placebo. Patients were studied polysomnographically under double-blinded conditions for 2 nights in each phase of the protocol. On an average dose of 15.9 mg oxycodone (equivalent to approximately three 5-mg tablets of commercial preparation), there was a statistically significant reduction in the number of periodic limb movements in sleep [(PLMS)/hour sleep (p < 0.004)] and in the number of arousals/hour sleep (p < 0.009) on drugs as compared to baseline or placebo. A statistically significant improvement was also noted in sleep efficiency (p < 0.006) and 10 of the 11 patients preferred oxycodone over placebo. We conclude that oxycodone is an effective treatment for RLS and PLMS. PMID- 8341894 TI - Circadian sleep regulation in the absence of light perception: chronic non-24 hour circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep wake schedule. AB - Sleep disturbances and the failure to entrain circadian rhythms to the 24-hour day have been reported in the majority of totally blind subjects. The present case study of a totally blind man with a well-documented recurring sleep disturbance was designed to investigate the mutual relationship between sleep and the circadian timing system. The 63-year-old subject, a high school teacher with a regular work schedule, had suffered from cyclically recurring insomnia for the past 28 years. Analysis of a sleep log that he had kept for the past 15 years suggested that his circadian rhythms were not entrained to the 24-hour day. During a 3-month inpatient study, the period of the endogenous circadian pacemaker was assessed by analysis of ambulatory core body temperature, urinary excretion and a series of estimates of the phase of core body temperature cycles and plasma cortisol levels during constant routines. All circadian markers revealed periods in the range of 24.22-24.27 hours, with no evidence for a modulation of the observed periods by the sleep-wake cycle. During this 3-month inpatient study, a complete cycle of the subject's sleep disturbance and remission was polysomnographically documented while the subject lived on a regular 24-hour schedule. Because the subject's circadian rhythms were free running and his sleep times were fixed, sleep occurred at virtually all circadian phases. Analysis of sleep latency, REM sleep latency, sleep duration, wake in sleep episode and REM sleep during sleep episode revealed a strong modulation by circadian phase. These findings in this blind man suggest that: 1) the period of his cyclically recurring sleep disturbance is directly related to the nonentrained period of an endogenous circadian pacemaker that drives circadian variation in core body temperature, urinary excretion, plasma cortisol and sleep propensity; 2) both his sleep structure and the severity of his daily sleep disruption are directly related to circadian phase and 3) his circadian pacemaker, which has an endogenous period that deviates only 0.2-0.3 hours from 24 hours, cannot be entrained by periodic daily exposure to nonphotic time cues, including a very regular 24-hour sleep-wake schedule. PMID- 8341895 TI - Consulting about insomnia: a method and some preliminary data. AB - Sleep specialists are increasingly asked to advise other health care workers and patients about specific cases of insomnia, even when the patients do not plan to seek actual treatment of their insomnia at a sleep center. This paper describes a procedure for such one-time consultations. It also provides some preliminary data on the subjective efficacy of such insomnia consultations by reporting data from follow-up telephone calls placed 1, 3 and 12 months after the interview. The patients' estimates of their sleep seemed significantly improved on all three follow-up contacts, and the telephone calls also provided information on what type of recommendations were actually tried by the insomniacs and which ones seemed beneficial. Acceptance of individual sleep hygiene suggestions ranged between 68 percent and 11 percent, but those who tried a given suggestion generally reported its usefulness to be about 70 percent. Advice to seek relaxation or behavioral therapy and suggestions for various medication changes were accepted by about half of those insomniacs who received such advice, and about two-thirds of those who tried them reported them as being helpful. Advice to seek psychotherapy--although quite carefully given--typically was tried by only one-third of those who received it. Overall, the survey shows good patient acceptance of once-only insomnia consultations. PMID- 8341896 TI - Aerobic fitness, acute exercise and sleep in older men. AB - In the current study 12 aerobically fit and 12 sedentary older men underwent two nocturnal polysomnographic (PSG) studies. A control PSG was conducted following a day without aerobic activity, whereas a postexercise PSG study was conducted following an afternoon session of exhaustive aerobic exercise. In addition to deriving usual sleep parameters, a computer scoring program was used to count the number of individual electroencephalographic (EEG) slow waves in each PSG tracing. Multivariate and univariate analyses showed that the fit subjects had shorter sleep onset latencies, less wake time after onset, fewer discrete sleep episodes, fewer sleep stage shifts during the initial portion of the night, less stage 1 sleep, a higher sleep efficiency and more total slow waves during both PSGs than did the sedentary subjects. Although no main effects were found for the acute exercise challenge, post hoc analyses showed that high levels of body heating during exercise predicted increased sleep fragmentation for both fit and sedentary subjects. These findings provide initial support for the contention that exercise and fitness may have significant effects on the sleep of older men. However, results also suggest that high levels of body heating resulting from a single exercise challenge may have adverse effects. Implications of the study are discussed and suggestions for future research are provided. PMID- 8341897 TI - Sleep and breathing patterns in patients with Prader Willi syndrome (PWS): effects of age and gender. AB - Patients with Prader Willi syndrome (PWS) often complain of daytime hypersomnolence. Because of reported daytime sleepiness and high prevalence of morbid obesity, these patients have been considered at risk for sleep related disordered breathing, but polysomnographic studies have been limited. We evaluated sleep and breathing polysomnographically in 24 PWS patients including 15 adults and 9 children. All adult patients completed MSLT testing on the day following the nocturnal sleep study. Both adult and children groups showed little or no sleep apnea, but REM related oxygen desaturation was quite common, its severity significantly correlated with increased obesity. Sleep patterns in both groups showed abnormal REM sleep cycles with variable REM latency (at times significantly shortened) and fragmented REM sleep with multiple brief REM periods. REM sleep abnormalities were still present in some patients without REM related desaturation. As a group, patients with PWS demonstrated pathological somnolence as measured by MSLT, which correlated with nocturnal sleep efficiency but not with nocturnal REM latency. It is hypothesized that the abnormal sleep findings in PWS reflect an underlying hypothalamic dysfunction characteristic of this syndrome. PMID- 8341898 TI - Sleep and mammalian hibernation: homologous adaptations and homologous processes? AB - Evidence from electroencephalographic, thermoregulatory and cellular neurophysiological studies suggests that sleep and hibernation may be homologous adaptations for energy conservation. However, despite the similarities between non-rapid eye movement (NREM) sleep and hibernation, the restorative function normally associated with slow wave sleep appears not to occur during hibernation, perhaps because of the low body temperature (Tb). Cellular neurophysiological studies also suggest that a bout of hibernation is not exclusively NREM sleep but is punctuated by periods of wakefulness. The entrance to hibernation involves both an inhibition of cortical activity and activation of hypothalamic regions, whereas the arousal from hibernation is primarily a hypothalamic function. Multiple neurochemical systems are affected by the arousal state change that occurs in hibernation, and a serotonergic-opiatergic interaction, in particular, may be important in regulating these events. Among regulated physiological systems affected by arousal state changes, the episodic respiration evident in hibernation shows striking similarities to the apneas observed during sleep in both humans and other mammals. Although the slight down-regulation of Tb and metabolism that accompanies the transition from wakefulness to NREM sleep may have served as a preadaptation for the evolution of hibernation among the mammals, increasing consideration must be given to the possibility that hibernation represents an arousal state distinct from any known normothermic arousal state. PMID- 8341899 TI - Are infants sharing a bed with another person at increased risk of sudden infant death syndrome? PMID- 8341901 TI - Bibliography of recent literature in sleep research. PMID- 8341900 TI - Respiratory problems during sleep in infants and the elderly and possible relation to mattress compression. PMID- 8341902 TI - [Schistosoma, water and man]. AB - The biology of schistosomes is increasingly better known due to the research works conducted since the early 1980s. Numerous data have been collected on: the structure of the genome; the genetic variability of natural populations; the causes of geographical distribution of Schistosoma species; the acquisition, probably recent, of the parasite as by modern man's ancestors; and even some aspects of development, such as the behaviour of larvae and the migrations in the circulatory system. Substantial advances have also been made in the maintenance of laboratory strains. Yet, multiple and fascinating problems are still raised by schistosomes. In the present state of our knowledge the origin and relationship of human parasitizing species are still hypothetical. Several features of reproduction, such as the existence of separate sexes and permanent couples cannot be explained. Quantitative data concerning the dynamics of transmission are much too vague to establish satisfactory mathematical models and to contribute usefully to strategies of control. Finally, the fact that schistosomes can develop either in man alone or in numerous mammals remain a mystery for immunologists and specialists of evolution. PMID- 8341903 TI - [Epidemiology of human bilharziasis]. AB - Schistosomiasis is endemic in three continents: Africa, where Schistosoma haematobium, S. mansoni and S. intercalatum are present; tropical America and some of the the Caribbean islands, where the only parasite of this type is S. mansoni; Mediterranean Asia (S. haematobium, S. mansoni) and the Far-East (S. japonicum, S. mekongi). Schistosomal infestation is distributed in foci of warying size and significantly differs in prevalence, intensity and therefore morbidity from one region to another. Despite the successes obtained in the neutralization of certain foci, the great plasticity of the hosts-parasites molluscs relations and the huge displacements of human populations in the poorer countries explain why the epidemiology of schistosomiasis is constantly changing and the disease is far from disappearing. PMID- 8341904 TI - [Symptoms and development of Schistosoma mansoni infestation]. AB - Schistosoma mansoni schistosomiasis is widespread in Latin America and Black Africa. Infestation is through the skin where it produces erythema with pruritus. Invasion is manifested by mild or sometimes fairly marked systemic disorders. The gastrointestinal disorders observed in the established phase have no characteristic features. The major complication is portal hypertension due to the portal vein fibrosis provoked by schistosomatic granules with an egg at their centre. The diagnosis rests on the finding of eggs in the faeces and on biopsy of the rectal mucosa. The present treatments are effective and well tolerated, but a portocaval anastomosis may be necessary. PMID- 8341905 TI - [Symptoms and development of Schistosoma haematobium infestation seen in a metropolis]. AB - Urogenital schistosomiasis is often diagnosed in France where, contrary to its severity, its initial presentation (mainly haematuria) has not changed. The frequency of major renal abnormalities seems to have diminished since 1965, but above all cystoscopy and intravenous urography have been superseded by ultrasonography, a totally harmless and painless method which provides the same information as that obtained with the previous two methods, except as regards the ureters. In particular, cystoscopy is now indicated only when tumours of the bladder are suspected at ultrasonography. Cutaneous schistosomiasis, with its characteristic features, deserves to be known and recognized. PMID- 8341906 TI - [Bilharziasis caused by Schistosoma intercalatum, a recent and forgotten form of schistosomiasis]. AB - Schistosoma intercalatum schistosomiasis is confined to the western regions of equatorial Africa. It is often asymptomatic but it produces microscopic lesions in the intestine (mainly the rectum), the liver and the genital organs of both men and women, the latter lesions being more insidious and insufficiently explored. Its treatment, like that of other schistosomiases, consists of one course of praziquantel. Naturally, S. intercalatum may be hybridized with S. haematobium in Gabon and Cameroun which are the two countries where the two parasites coexist. PMID- 8341907 TI - [Acute form of primary bilharziasis]. AB - Acute schistosomiasis is observed in subjects with primary infestation, Schistosoma mansoni and S. japonicum being the responsible parasites in the vast majority of cases. The disease occurs between 2 weeks and 6 months from the first infesting bath and presents as fever with cutaneous, pulmonary and gastrointestinal manifestations. Eosinophilia is frequent. The diagnosis is made by serological tests. Myelopathies are rare and may leave severe sequelae. Treatment rests on praziquantel combined with a short course of corticosteroid therapy. PMID- 8341908 TI - [Biological diagnosis of Schistosoma infestation]. AB - For general practitioners the most important step towards the clinical and laboratory diagnosis of infestation with Schistosoma spp. is to think of it. Although schistosomiasis is the world's most frequent parasitosis after malaria, it is found in France only as imported cases (immigrants, tourists, etc.) with clinical signs that are not always very suggestive at the stage of invasion. The laboratory examinations requested can then make the diagnosis, irrespective of the time elapsed since infestation. In the early invasion stage, only the indirect serological methods (ELISA, IFI, precipitation techniques) are appropriate. The direct methods are not always informative since the parasites are still immature and do not lay eggs. But when the disease is established the diagnosis rests essentially on direct examination of urine and faeces which discloses schistosoma eggs the morphology of which varies from one species to the other. PMID- 8341909 TI - [Salmonella-Schistosoma interactions]. AB - Prolonged or recurrent typhoid fever and mainly salmonella septicaemia usually regarded as minor, or even episodes of salmonelluria are not uncommon in patients infested with Schistosoma spp. In such cases the salmonella infection is often apparently resistant to antibiotic therapy. Schistosoma-salmonella interactions have been described with all species of schistosoma, notably S. haematobium, S. mansoni, S. intercalatum and S. japonicum. The adult worms of schistosoma live in the mesenteric venous plexuses and, in some particular sites, salmonellas are electively stuck onto the outer wall of adult schistosomas. As a result of this, salmonella septicaemia is facilitated and sustained by the schistosomal infestation, and several varieties of salmonella may be involved. These salmonella infections cannot be cured without treatment of the associated schistosomiasis. PMID- 8341910 TI - [Treatment of bilharziasis]. AB - Specific treatment of bilharziosis is obviously simplified by praziquantel which, unfortunately, is not easily available in endemic areas. Nevertheless, the major problem is an early treatment before the occurrence of severe sequellae. Mass chemoprophylaxis remains needed and, if possible, with praziquantel. For economic purposes, we have often to use either oxamniquine or niridazole-metrifonate combination. PMID- 8341911 TI - [Vaccine against bilharziasis. Strategies and perspectives]. AB - Due to the determination of immunity acquisition mechanisms, a number of studies on experimental models and human populations has made it possible to devise a strategy of vaccination against schistosomiasis, a major worldwide parasitic disease affecting 200 million people. A schistosomial protein, identified as glutathione-S-transferase (SM28GST) has been cloned and expressed in various vectors. Immunization with the recumbent protein results in a significant reduction of the parasitic load, while the fertility of schistosoma and the viability of its eggs are markedly inhibited. Recent experiments performed in primates and bovines have shown that a more than 90% inhibition of the schistosoma's transmission potential can be induced by this vaccine. The important role played by IgA antibodies in the inhibition of the parasite's fertility has led to the development of an oral immunization strategy. In view of the results obtained, the availability, in the near future, of a vaccine protecting human beings against this scourge can be considered realistic. PMID- 8341912 TI - [The campaign against schistosomiasis]. AB - Like other diseases linked to environment from where men look for supplies of goods, schistosomiases are difficult to control. Means of control are existing (mass treatment, selective treatment, with well tolerated drugs) but to insure the decrease of the prevalence over a long period of time, the strategies are sophisticated and often expensive. Therefore, today the objectives of schistosomiasis control are focused on the prevention and decrease of morbidity rather than on the decrease of transmission. Especially so when the economic, social and cultural levels do not permit to avoid the "pathogenic" behaviours. PMID- 8341913 TI - [Preoperative cardiologic evaluation. More limited indications, for more useful results]. PMID- 8341914 TI - [Modern identification principles in forensic medicine. Major progress through informatics and molecular genetics]. PMID- 8341915 TI - [Treatment of pneumonia in a community]. PMID- 8341916 TI - [Heredity and cancers]. AB - Cancer is a disease at the DNA level, originating from mutations of genes involved in the regulation of cell proliferation and differentiation: oncogenes and tumor suppressor genes. Only a few proportion of tumors, resulting mainly from germ-line anti-oncogene inactivation, arise in the frame of inherited cancer syndromes with mendelian mode of transmission. There may also be a much larger number of cases who are less strongly predisposed, without evident familial clustering. Genes involved in DNA repair process and in metabolism of carcinogenesis may be responsible. Study of genetic predisposition to cancer have important implications for screening individuals at high-risk in families. PMID- 8341917 TI - [Wounds of the hand. Diagnosis, treatment in the first 24 hours]. PMID- 8341918 TI - [Functional intestinal disorders. Diagnosis, treatment]. PMID- 8341919 TI - [Shoulder injury. Diagnostic orientation]. PMID- 8341920 TI - [Dermatophyte infections of the hairless skin and folds. Diagnosis and treatment]. PMID- 8341921 TI - [Pneumothorax. Principles of emergency treatment]. PMID- 8341922 TI - [Deficiency rickets. Physiopathology, diagnosis, preventive and curative treatment]. PMID- 8341923 TI - [Foreign bodies in the airways. Diagnosis and treatment]. PMID- 8341924 TI - [Cytokines and inflammation]. AB - Numerous cytokines are present in inflammatory foci. Two of them, interleukin-1 (IL-1) and tumour necrosis factor (TNF), play a major role in coordinating mechanisms which command inflammation. Under their action many cells produce lipidic mediators, proteolytic enzymes or free radicals, all factors that are directly responsible for the noxious effects observed. IL-1 and/or TNF exert cytotoxic activities on vascular epithelium, cartilage, bone, muscle or beta cells of pancreatic islets. Such cytokines as interferon gamma (IFN gamma), IL-3 or granulocyte-macrophage colony stimulating factor (GM-CSF) amplify the inflammatory response by increasing the production of IL-1 and TNF by macrophages. GM-CSF also produces other cytokines, such as IL-8 and the macrophage chemoattractant protein 1 (MCP-1), the chemotactic properties of which participate in the recruitment of leucocytes within the focus of inflammation. IL 6 abounds in inflammatory processes and induces the production by hepatocytes of acute inflammation phase proteins. The same applies to IL-1, TNF, IL-11, the leukaemia inhibitory factor (LIF) or the transforming growth factor beta (TGF beta). The latter also possesses a number of anti-inflammatory activities and, like IL-4 and IL-10, can inhibit IL-1 and TNF production. Glucocorticoids have this potential activity, and they may be produced by a cascade of events initiated by IL-1, TNF and IL-6, involving the neuroendocrine system. The concept of "cytokine network", therefore, perfectly illustrates the participation of these mediators in inflammatory mechanisms. PMID- 8341925 TI - [Cytokines and hematopoiesis]. AB - The identification and purification of haemopoietic growth regulators have resulted in a better understanding of control mechanisms. Cloning and expression of the corresponding genes have shown that most of the activities observed correspond to specific glycoproteins produced by cells from numerous tissues, including those of bone marrow stroma and immune system. These cytokines activate the responsive cells through specific receptors expressed on their membranes. They exert an accurate control of haematopoiesis in a network of synergistic and antagonistic factors. The exact identification of their biological activities, together with the possibility of producing them in large amounts by genetic recombination, have already resulted in their therapeutic use with, in certain cases, a remarkable efficiency. PMID- 8341926 TI - [Cytokines and severe sepsis]. AB - During severe sepsis syndromes, almost every gene coding for cytokines may be activated. The primary purpose of this activation is to defend the organism against infection, but sometimes these inflammatory mediators go out of control. The reasons why this may occur is unclear because the regulation of cytokines production is still poorly understood. Metabolic effects, production of endothelial adhesion molecules and triggering of neutrophils are some important consequences of cytokine overstimulation which may lead to the clinical picture of septic shock. The major cytokines involved in septic shock are tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1). Both may induce lethal shock in experimental models. The effects of these 2 cytokines are difficult to differentiate from one another because they share many similar biological effects, one can induce the synthesis of the other, and they are strikingly synergistic with each other. gamma-interferon may amplify the inflammatory response by stimulating the cells of monocytic lineage and by increasing TNF receptor expression, thus participating in the pathogenesis of the septic syndrome. The role of other cytokines is still poorly known. Clinical studies with anti-TNF monoclonal antibodies or with an IL-1 receptor antagonist are under way. PMID- 8341927 TI - [Cytokines and malignant hemopathies: leukemias and bone marrow graft]. AB - Cytokines are now part of the modern armentarium utilized against malignant blood diseases. The essentially lymphocytic haematopoietic growth factors (G-CSF, GM CSF, IL-3) reduce the infectious morbidity associated with the deep and prolonged neuropoenia induced by the myelo-ablative conditioning for autologous or allogeneic bone marrow transplantations, and widening their indications is tempting. The reluctance expressed about their use in chemotherapy of acute myeloid leukaemia is abating now that controlled studies have shown that they preserve the complete response rate and shorten the duration of leucopoenia. Moreover, they modify the leukaemia biological response, which makes it possible to increase the cytotoxicity of certain drugs and constitutes a new approach to drug-resistant leukaemias. Immuno-modulating cytokines (interferon alpha, interferon gamma, interleukin-2) act through mechanisms that are still ill defined: antitumoral activity, modification of biological responses, immunoactivation. Nevertheless, interferon alpha has revolutionized the treatment of hairy cell leukaemia and myeloid leukaemia, with a 70% remission rate. The scarcity of complete responses (10% of hairy cell leukaemias) or cytogenetic responses (20% of chronic myeloid leukaemias) justifies a combined treatment (chemotherapy+immunotherapy?) to improve these patients' cure rate. The anti leukaemic activity of interleukin-2, observed in patients with refractory relapses, produces 33% of responses, including 10% of complete responses, and it is tempting to test the impact of this immunotherapy on the control of residual leukaemia as adjuvant of complete remission using randomized trials. PMID- 8341928 TI - [Anti-cytokines and anti-cytokine receptors]. AB - Cytokines play a key-role in the immune response. The best known of them is interleukin-2 and its specific receptors. Monoclonal antibodies directed against the interleukin-2 receptor have initially enabled this receptor to be characterized; then they served to confirm the major role played by this cytokine in immune responses, where it proved effective in many animal models such as allograft reaction, delayed hypersensitivity reaction and some experimental auto immune diseases. These results have been confirmed in man, particularly in kidney transplantation (but also in bone marrow transplantation), and they encourage to develop new bioreagents (chimeral antibodies, "humanized" antibodies, fusion proteins). Some of these reagents are now undergoing evaluation in renal transplantation. The principles of these bioreagents, issued from molecular biology, can be applied to other cytokines involved in the immunopathological mechanisms of certain diseases such as, for example, IL-6 and its role in the development of myeloma. Data from immune intervention directed against other cytokines are, for the moment, preliminary, but many potential targets (IL-1, IL 4, TNF alpha, INF gamma) are emerging. PMID- 8341929 TI - [Cytokine assay: value and limitations]. AB - Cytokines are proteins with multiple functions indispensable to body homeostasis. They are also good indicators of certain diseases which they are sometimes suspected to induce (e.g. septic shock, allograft rejection). Making cytokine assay methods available to scientists and clinicians has been a notable step forward in the understanding of numerous illnesses. However, these quantitative assays create more problems than they solve, and although reliable and easy tests exist we cannot recommend their use in routine clinical practice. In 1992, cytokine assays must be reserved for research studies where their results in patient populations are meaningful and where they can usefully be completed by other detection methods, such as amplification by polymerase chain reaction or hybridization in situ. Nevertheless, the constant improvement of assay kits, the ever increasing number of cytokines that can be quantified by simple laboratory tests and a better study of interactions between cytokines, their soluble receptors and their natural inhibitors will perhaps make it possible, in the near future, to analyse finely the immune response in not very invasive samplings. Moreover, there are hopes that modern molecular biology tools will soon be available in daily clinical practice. For instance, the development of automated methods for amplification by polymerase chain reaction will provide useful information on the activation of the immune system in various clinical situations. Such techniques, combined with measurements of local or circulating cytokine concentrations are undoubtedly promising tools. Finally, cytokine assays are essential to research workers who can study, within well-defined systems, the kinetics of production and the respective role played by these mediators. PMID- 8341930 TI - [The cost of cytokines]. AB - The use of cytokines (interferons, interleukin-2, growth factors) is in full development, but the new drugs issued from biotechnology are costly. In order to control consumption, these products are made available only to hospital pharmacists, and they are paid by the prescribing establishments from global funds. This results in an ever growing financial burden on the hospital pharmaceutical budget. Physicians will have to conciliate 2 objectives: make the patients benefit from the new drugs, and control the expenses by using these drugs only when necessary. PMID- 8341931 TI - [Congestive outbreak of osteoarthritis. Chondrolysis and cartilage repair]. PMID- 8341932 TI - [Management of acute carbon monoxide poisoning. Normobaric or hyperbaric oxygen]. PMID- 8341933 TI - [Endovascular ultrasonography. A technology with a promising future]. PMID- 8341934 TI - [Treatment of infections developing on catheters]. PMID- 8341935 TI - [Contact dermatitis. Etiology, physiopathology, diagnosis, treatment]. PMID- 8341936 TI - [Acute metabolic complications of diabetes (ketoacidosis, hypoglycemia, hyperosmolarity). Etiology, physiopathology, diagnosis, emergency treatment of ketoacidosis with posology]. PMID- 8341937 TI - [Epistaxis. Diagnostic orientation and principles of the emergency treatment]. PMID- 8341939 TI - [Nephrotic syndromes. Physiopathology, diagnosis, clinical course and treatment of lipoid nephrosis]. PMID- 8341938 TI - [Malignant tumors of the larynx and the hypopharynx. Epidemiology, diagnosis, treatment]. PMID- 8341940 TI - [Lithium. Principles and rules of use]. PMID- 8341941 TI - [Ascites. Diagnostic orientation]. PMID- 8341942 TI - [Physiopathology and principles of intensive care in intestinal obstructions]. AB - The physiopathology of intestinal obstruction consists of increased intestinal peristaltis, distension by gas and fluids, contraction of the extracellular fluid volumes (plasma and interstitial sectors) and bacterial proliferation. To this must be added, in obstruction by strangulation, the passage of bacteria and bacterial products into the general circulation and the peritoneal cavity through an ischaemic or necrotic intestinal wall. Metabolic disorders consist of water, sodium and potassium deficits and acid-base disturbances. Water and electrolyte replacement should take into account the deficits that existed at the beginning of treatment, the additional losses expected during treatment and the needs for daily maintenance of water and electrolyte balance. The therapeutic procedure is simple provided it is systematized. PMID- 8341943 TI - [Acute intestinal obstructions in adults: quantified semiology (signs and their value) and surgical treatment]. AB - The prevalence of signs and symptoms of acute intestinal obstruction in the adult was studied in a prospective study of 600 cases extracted from a data base on acute abdomen in 7,000 patients. This study of prevalence allows a precise definition of intestinal obstruction syndrome and to differentiate two types of presentations according to the site of obstruction on the small bowel or the colon. However, it is more difficult to differentiate simple bowel obturation from vascular strangulation. Surgical treatment depends mainly on the cause of obstruction. PMID- 8341944 TI - [Chronic small intestine obstructions]. AB - Chronic small bowel obstruction may be related either to disordered motility or to progressive chronic stenoses. Disordered motility (or intestinal pseudo obstruction) is the consequence for muscular and/or intrinsic nerve impairment with 2 main types, one of which is primary (including so-called visceral myopathies and visceral neuropathies), the other one being secondary (generally due to systemic, or sometimes immunologic disease). Chronic stenoses have a different pathophysiology and occur in the setting of chronic inflammatory bowel disease or of systemic diseases such as vasculities. Chronic stenoses lead to intestinal stasis and in fine to mechanical obstruction. In any case, chronic obstruction poses difficult diagnostic and therapeutic problems. Management calls for tight medico-surgical cooperation. Atypical surgical operations may be warranted, and specific, sometimes aggressive medical care is mandatory. Moreover the nutritional consequences of chronic small bowel obstruction may become highly disabling due to alimentary restriction, disordered transit, bacterial overgrowth and malabsorption. In this setting nutritional support should be a matter of prime concern. PMID- 8341945 TI - [Imaging of intestinal obstructions]. AB - The diagnosis of intestinal obstruction still rests on radiography of the abdomen without preparation. Three X-ray films must systematically be taken: a general film and a film centred on the diaphragmatic domes with the subject standing; another general film with the subject lying on his back. It is relatively easy to identify the obstructed segment, but the cause of obstruction remains difficult to determine. For small bowel obstruction, emergency surgery is often necessary. If the patient's condition permits, it may be useful to opacify the dilated segment in order to study the nature of the obstacle. Colonic obstruction is opacified through the anus, this route being more informative. There are two types of acute obstruction: by occlusion and by strangulation. The various causes are considered, but there are also incomplete obstructions and dilatations without obstruction. PMID- 8341946 TI - [Postoperative obstructions]. AB - The intestinal obstructions after a laparotomy in adult may be caused by an inflammatory or a mechanic pathology; the incidence of the bowel obstruction in the early postoperative period is about 0.5 to 2% of all surgical procedures; these obstructions are often related to the degree of contamination or infection; contrary to postoperative paralytic ileus, they result in a reoperation, so as a peritonitis may be associated. In the later postoperative period intestinal obstructions may be caused by adhesions, internal strangulation or fibrosis bridles; these obstructions are frequent and they affect especially the small intestine (5% of laparotomies will be complicated by small bowel obstruction). The intestine volvulus due to bridles or adhesions is observed in approximately 10% of cases and the diagnosis must be conjured up in principle because it necessities an operation immediately; it's the same for the strangulation by incarceration. The absence of classic indicators of gangrene permits a non operative treatment using a naso-gastric tube decompression during 24 to 48 hours: generally the causes of obstruction are small bowel adhesions, nevertheless it's important to eliminate a colonic obstruction. The management of chronic postoperative adherences is a difficult problem because the iterative operations increase the risk of intestinal obstructions; the video-laparoscopic surgery seems to be a promising technique to prevent and to treat (laparoscopic adhesiolysis) the post-operative adherences; its results are not evaluated. PMID- 8341947 TI - [Obstructions in children]. AB - In matters of intestinal obstruction the younger the child, the clearer the features of this condition. As in adults, obstruction reveals an intestinal blockage related to multiple and varied origins. Neonatal obstruction deserves special attention, as it often reveals a digestive tract abnormality with interrupted continuity which is incompatible with life unless the appropriate surgical treatment is carried out. Constant advances in intensive care and nutritional care of these infants result in increasingly "borderline" digestive situations, but certain situations have not yet been solved in the absence of success of intestinal transplantation. PMID- 8341948 TI - [Ogilvie's syndrome and non-mechanical obstructions]. AB - Ogilvie's syndrome and chronic intestinal pseudo-obstructions are two aspects of non-mechanical obstruction. The syndrome consists of acute colonic obstruction due to multiple causes and is characterized by passive dilatation of the colon without downstream obstacle. Treatment is primarily medical, except in cases with complications such as perforation by symptomatic treatment and, sometimes, by decompression colonoscopy. The most severe complication is perforation of the colon which may require colonic excision. Chronic intestinal pseudo-obstruction is characterized by chronic disorders mostly due to abnormalities of nervous plexuses and smooth muscle of the small and large bowels. It occurs in children and surgical abstention may lead to repeated but unfortunately ineffective operations. The only treatment recognized is digestive tract bypass combined with total parenteral feeding. PMID- 8341949 TI - [Strangulated hernia and eventration]. AB - Incarcerated hernia or wound dehiscence are responsible for more than 10% of small bowel obstructions. The complication is easily recognized when hernia or wound dehiscence was previously diagnosed. Difficulties occur when mass is deeply located in a thick abdominal wall or inside the inguinal canal. Femoral hernias and direct inguinal hernias are those which strangulate the most. Strangulation in wound dehiscence is the most severe. Strangulated hernia should be routinely excluded in patient with intestinal obstruction, to avoid inappropriate surgical approach. PMID- 8341950 TI - [Tetrahydroaminoacridine or THA. Disputed value in Alzheimer's type dementia]. PMID- 8341951 TI - [Pubalgia. A syndrome in of sport injury, corresponding to locoregional pathology]. PMID- 8341952 TI - [Acquired facts on the treatment of colonic and rectal cancers]. PMID- 8341953 TI - [Role of cyclosporin in renal transplantation]. AB - The cyclosporine era started 10 years ago in organ transplantation, especially in renal transplantation. Following the pioneering works showing the efficacy and its synergism with other immunosuppressors, a second step consisted in a better use by decreasing the induction dose and a closer definition of its side effects. A major improvement in the results (increase of 5 to 10% in patient survival and of 10 to 20% in graft survival), a decrease in the number of acute rejection episodes, in the cumulative doses of steroids, in the duration of hospitalization and in the total cost of transplantation made this drug as the worldwide used agent, now considered as the milestone in immunosuppression. Over all, organ transplantation is needing a more specific immunological agent, deprived if possible of major side effects. In these regards, each new agent should be considered only if compared to the "gold standard", namely cyclosporine. PMID- 8341954 TI - [Segalen and Chabaneix in China during the Manchurian plague]. PMID- 8341955 TI - [Bacterial cutaneous infections: impetigo. Etiology, diagnosis, development, treatment]. PMID- 8341956 TI - [Painful shoulder. Diagnostic orientation]. PMID- 8341957 TI - [Leukorrhea. Diagnostic orientation]. PMID- 8341958 TI - [Typhoid and paratyphoid fever. Epidemiology, etiology, physiopathology, diagnosis, development, prognosis, treatment]. PMID- 8341959 TI - [Closed injuries of the abdomen. Physiopathology, diagnosis, treatment]. PMID- 8341960 TI - [Statural growth retardation. Diagnostic orientation]. PMID- 8341961 TI - [Pelvic rheumatic spondylitis. Etiology, diagnosis, development, prognosis, treatment]. PMID- 8341962 TI - [Cancer of the tongue. Epidemiology, diagnosis, treatment]. PMID- 8341963 TI - [Procurement and transplantation of organs. Legal and ethical aspects]. PMID- 8341964 TI - [Antiemetics during cytotoxic treatments]. PMID- 8341965 TI - [Inguinal, crural and umbilical hernia. Physiopathology, diagnosis, complications, treatment]. PMID- 8341966 TI - [Recent brain injury. Diagnostic orientation]. PMID- 8341967 TI - [Cutaneo-mucous herpes. Epidemiology, physiopathology, diagnosis, development, treatment]. PMID- 8341968 TI - [Chickenpox and herpes zoster. Epidemiology, physiopathology, diagnosis, development, treatment]. PMID- 8341969 TI - [Severe acute asthma. Diagnosis and emergency treatment with posology]. PMID- 8341970 TI - [Cancers of the stomach. Diagnosis, development, treatment]. PMID- 8341971 TI - [Intrapulmonary solitary round opacity. Diagnostic orientation]. PMID- 8341972 TI - [Paranoid personality. Diagnosis]. PMID- 8341973 TI - [Normal sperm]. AB - The evaluation of male infertility rationally begins with a study of the characteristics of the semen, notably sperm count and motility assessment. However, this examination is difficult to interpret due to the important intra- and interindividual variability of these parameters, making it impossible to determine accurately the criteria of "normality". In each given subject the characteristics of semen can be influenced by the conditions of sample collection, the length of abstinence, and any disease that may have occurred in the 3 months preceding the examination. To draw firm conclusions from one single examination would be misleading and a second examination is advised. The criteria of normality laid down by WHO are not very useful to determine the degree of fertility in males: one may speak of oligozoospermia when the sperm count is below 20 million/ml, but several recent prospective studies have shown that fertility significantly falls only below 5 million/ml. A threshold value concerning the percentage of normal forms has been established at 30-40%, whereas teratozoospermia has been defined by the WHO as from 50% onwards. Sperm count can be completed by a fine analysis of sperm motions, and this has been made possible by the development of digital microvideographic analysis techniques. However, defining norms for the main parameters of sperm motility is delicate and can only be done by teams of specialists. PMID- 8341974 TI - [Epidemiology of male infertility]. AB - The responsibility of the male in the infertility of the couple has been ignored for long time; it is now universally recognized and obliges general practitioners to explore the possibility of male infertility. Clinical and laboratory examinations must be carried out simultaneously, with a systematic search for the major risk factors of male infertility, such as varicocele and history of genital infection or injury to the testis. The practitioner must also investigate the working conditions and the environment of the infertile male in search for occupational risk factors which are frequently overlooked but often have severe consequences. PMID- 8341975 TI - [How to recognize and classify male infertility]. AB - Infertility of the couple affects 19% of the general population, 4% of which are infertile. Almost 50% of infertilities are ascribable to the male partner. Male infertility is determined by a preliminary clinical and biological evaluation which consists of full examination of the semen, with sperm and spermocyte counts and cultures. Further examinations depend on the data provided by this evaluation. The causes of human infertility can be classified as follows: 1. Abnormalities of the spermatozoa which may be of testicular origin (defect of gonadal maturation, genetic of genic congenital anomalies, varicocele) or of post testicular origin (acquired or congenital excretory obstacle to be located by surgery and treated whenever possible. 2. Abnormalities of seminal plasma (seminal infections, autoimmunization, isoimmunization). 3. Abnormalities of ejaculation (pathogenic or iatrogenic retrograde ejaculation, organic or psychic anejaculation). 4. Unknown cause requiring more sophisticated sperm examinations, such as microvideography of the flagellum, exploration of the acrosome and of nuclear maturation. PMID- 8341976 TI - [Exploration of pathological sperm and its fertilizing power]. AB - The exploration of human sperms has considerably progressed during the last few years, side by side with the development of medically assisted procreation techniques. The sperms are explored by a battery of techniques which evaluate their functional state and the expression of their fertilizing power. Sperm count and motility assessment remain the basic examination in the exploration of couples' infertilities but other more sophisticated techniques can be used to evaluate certain stages in the fertilization process, including the recognition by, and attachment of the sperm to the zona pellucida of the oocyte, its penetration into this zone, the fusion of sperm and oocyte membranes and the transformation of the nucleus into a male protonucleus in the cytoplasm of the oocyte. Up to now, however, most of the techniques that evaluate the functional state of the sperm cell have not been predictive, and the only feasible and repeatable means of evaluating the fertilizing power of a semen is fertilization in vitro. PMID- 8341977 TI - [Male infertility of immunologic origin and its treatment]. AB - Antibodies against sperm surface antigens may be responsible for 3 to 20% of idiopathic male infertility cases. Antisperm immunisation may be suspected in view of a clinical suggestive history, a spontaneous sperm-agglutination and an inability of spermatozoa to penetrate a normal cervical mucus. The responsibility of antisperm antibodies in the infertility state could be demonstrated in vitro by their effects on several sperm functions. An inverse correlation between antibodies titres and conception rates has been demonstrated and it justifies a therapeutical approach in the presence of high levels of antibodies. Corticosteroids must not be used as the results obtained did not justify the side effects observed. Intra-uterine insemination as well as in vitro fecundation can help some of these couples but results must be improved by better methods of selection of motile sperm populations devoid of antibodies. PMID- 8341978 TI - [Genetic aspects of male infertility]. AB - Cytogenetic investigations in sterile males showed that autosomal and sex chromosome anomalies can be responsible of the defect of spermatogenesis. Specific alteration of genes controlling spermatogenesis is excluded because all chromosomes are involved in the anomaly and breakpoints are distributed at random. In the aim to explain the spermatogenic failure, three mechanisms are proposed: X-autosome interaction, asynapsis, somatic lesion of the gonad, each mechanism might act alone or with the other. Beside chromosomal infertility, meiotic or sperm anomalies suggest the presence of gene mutations which interfere with the evolution of spermatogenesis or lead to the formation of abnormal spermatozoa. Insertion of technics of molecular biology in our researches could demonstrate the existence of these mutations; the same technics will allow to resolve the problem of the failure of a germ cell bearing a chromosomal anomaly particularly when this anomaly is balanced and involves the autosomes and not the sex chromosomes. PMID- 8341979 TI - [Medical treatment of male infertility]. AB - The opinions of specialists on the medical treatment of male infertility has been altered by two events: the advent of epidemiology, which demands studies with control cases, and the advances achieved in in vitro fertilization. Apart from cases of hypogonadotropic hypogonadism, no type of male hypofertility has found an unquestionably effective treatment. Yet it is probable that varicocelectomy, treatment of genital infection and, in rare cases of hormonal deficiency, hormonal treatments that stimulate Leydig and Sertoli cells may have positive effects. In idiopathic oligo-astheno-teratospermia, which is the most frequently encountered type of infertility, several treatments are currently being tested but have not been fully evaluated. Quite recently, attempts at treating patients immediately before in vitro fertilization have started, but the results are not yet available. PMID- 8341980 TI - [Psychological approach of the infertile male]. AB - Male infertility is usually anxiogenic, and it is often responsible for sexual dysfunctions due to the cultural indissociability of the virility and fertility concepts on the one hand, and to the timing of sexual intercourse in the ovulation period on the other hand. The intrusion of medicine in the life of the infertile couple frequently amplifies the existing psychological problems and discloses other problems by questioning the representation systems of identity, procreation and filiation. PMID- 8341982 TI - [Future of the treatment of male infertility]. AB - The aim of this paper is to introduce inherent difficulties leading to relative delay in the field of male infecundity treatment. Four theoretical possibilities are exposed: infertility prevention improvement, qualitative or quantitative improvement of spermatogenesis, spermatozoa fecundity ability improvement and micro-fertilization procedures. These methods are exposed in their technical aspects and in their results. Critical analysis is conducted about some impressive reported series. Basic knowledge improvement seems to be necessary to explore new therapeutic ways. PMID- 8341981 TI - [Assisted procreation for male indication]. AB - Strategy for male infertility looks like a compromise between diagnosis methods with their efficacy and complexity and treatment with their own risks, cost, efficacy. Infertility duration as well as woman's fertility play a key role for such a strategy. Definitive infertility without any correction (secretory azoospermia) will be proposed for alternate projects. Some situations may benefit from specific therapy (hypogonadotropic hypogonadism, anejaculations or retrograde ejaculation). More frequently male hypofertility is suspected with non specific sperm alterations, then assisted reproductive technologies will be discussed. Intra-cervical way artificial insemination with husband semen may be proposed in case of hypospadias, anejaculation, retrograde ejaculation, small volume ejaculate or self-cryostored semen, however negative post-coital test, positive crossed penetration test and positive post-insemination test need to be confirmed. Intrauterine way enhance fertilizing probability by discarding cervical step. It will be justified in case of negative post-coital test as well as crossed penetration test except that sperm preparation allowed to inseminate 500,000 to 1 million motile spermatozoa. Both rigorous monitoring and synchronism between insemination and ovulation enhance the efficacy of IU AIH which allowed a two to four fold increase in the pregnancy rate on a total of six cycles. In vitro fertilization for male factor represent around 15% of all IVF attempts. Both decrease in the fertilization rate and the increase in the pregnancy rate by transfer as compared with tubal factor are well accepted. The fertilization failure remain difficult to explain and need to be cautiously confirmed. Thus IVF represent an actual fertilization test but remain limited by the heterogeneity of parameters under "male factor".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341983 TI - [Sodium and arterial hypertension. Mythic or real relations?]. PMID- 8341984 TI - [MRI in the exploration of tendon diseases. An irreplaceable tool with still limited indications]. PMID- 8341985 TI - Role of acid inhibition in the management of Helicobacter pylori infection: chairmen's introduction. PMID- 8341986 TI - Hp and pH: implications for the eradication of Helicobacter pylori. AB - Helicobacter pylori infection causes inflammation of the gastric and duodenal mucosae, which results in a disturbance of the regulatory mechanisms for gastrin, gastric acid and pepsin secretion. Acid secretion may be decreased, normal or increased, depending on the stage of infection, although the meal-stimulated gastrin response is invariably elevated. The exact mechanisms involved are not known but may be due to the release of cytokines in response to bacterial toxins. H. pylori colonization is reduced by effective acid suppression with proton pump inhibitors, although it is not eradicated. In combination with amoxycillin, omeprazole, up to 40 mg twice daily, eradicated the organism in up to 82% of cases. This synergistic effect may be due to a direct effect of omeprazole on the organism, the protection of amoxycillin from acid degradation, or enhancement of host defence mechanisms accompanying acid suppression. PMID- 8341987 TI - Long-term follow-up after eradication of Helicobacter pylori with a combination of omeprazole and amoxycillin. AB - Early studies have suggested that omeprazole may facilitate the eradication of Helicobacter pylori. Sixty patients with duodenal ulcer and H. pylori colonization were randomly assigned to receive either omeprazole monotherapy (n = 30) or combination therapy with omeprazole and amoxycillin (n = 30) for a total duration of 6 weeks. Four patients receiving monotherapy and three receiving combination therapy had to be withdrawn from the study. All (100%) duodenal ulcers healed in patients receiving combination therapy, and 25 out of 26 (96%) healed in the group receiving monotherapy. H. pylori was eradicated in 22 out of 27 (82%) patients receiving combination therapy; only two ulcer relapses (9%) occurred within 18 months in these 22 patients. Of the five patients who remained H. pylori-positive after combination therapy, two relapsed during the 18-month follow-up. In the monotherapy group, all patients remained H. pylori-positive after treatment, and duodenal ulcer relapsed in 16 out of 25 (64%) patients within the median follow-up of 18 months. Adverse events were not reported in the group treated with combination therapy; one patient receiving monotherapy reported severe headache. These results lend further support to existing data that H. pylori eradication prevents duodenal ulcer relapse and show that combination therapy with omeprazole and amoxycillin is effective and well tolerated. PMID- 8341988 TI - Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer. AB - Helicobacter pylori is the major causal factor in chronic gastritis. Its acquisition leads to a chronic, usually lifelong, inflammation of the gastric mucosa, which may gradually progress to atrophy (with intestinal metaplasia) in a significant proportion of infected individuals. This progression is probably multifactorial, being influenced by genetic or environmental factors in addition to H. pylori infection. The pathogenesis of peptic ulcer and gastric cancer is closely associated with H. pylori gastritis and its subsequent atrophic sequelae (atrophic gastritis). H. pylori-induced gastritis is an important risk factor in the multifactorial aetiology of these diseases. It causes a cascade of reactions that damage the gastric mucosa and epithelium in various ways. The specific mechanisms involved are largely unknown. Some are probably bacterium-related reactions, which are influenced by various virulence factors, and others are consequences of the mucosal inflammation and atrophy. The risk of peptic ulcer and gastric cancer in patients with H. pylori gastritis can be summarized as follows: i) the risk of both peptic ulcer and gastric cancer is low in individuals with a normal stomach; ii) the risk of peptic ulcer is approximately ten times higher and the risk of gastric cancer approximately twice as high in patients with non-atrophic H. pylori-positive gastritis as in those with a normal stomach; iii) these risks are further increased (twofold to threefold) when there is antral atrophy; whereas iv) in the presence of corpus atrophy the risk of gastric cancer remains high, but that of peptic ulcer decreases gradually to zero with increasing severity of corpus atrophy. PMID- 8341989 TI - Compliance, adverse events and antibiotic resistance in Helicobacter pylori treatment. AB - The highest H. pylori eradication rates have been reported with triple therapy, using metronidazole with amoxycillin or tetracycline, and colloidal bismuth subcitrate or bismuth subsalicylate. The use of such therapies, however, may be impeded by a number of major disadvantages, including reduced patient compliance, the incidence of adverse events and primary or acquired antibiotic resistance. Patient compliance is a particular problem with triple therapy owing to the quantity of drugs taken, treatment duration and regimen complexity; the eradication rate is reduced from 96% to 69% when only 60% of the medication is taken. The risk of adverse events resulting from the inclusion of antibiotics in the regimen is increased in triple therapy, and this generates reluctance in many practitioners to prescribe such therapy despite its well-documented efficacy. An important cause of antibiotic failure lies in the development of H. pylori resistance; between 6% and 27% of H. pylori strains are primarily resistant to the 5-nitroimidazoles--metronidazole and tinidazole--both of which are used in triple therapy. In contrast, no resistance of H. pylori to amoxycillin has been reported. The combination of an acid pump inhibitor with a single antibiotic represents a promising novel therapy for H. pylori-associated peptic ulcer disease. Treatment with omeprazole and amoxycillin could provide both rapid healing of ulcers and eradication of H. pylori, coupled with few adverse events, good drug compliance and low ulcer relapse rates, and may replace triple therapy as first-line medication. PMID- 8341990 TI - Eradication of Helicobacter pylori and its effect in peptic ulcer disease. AB - Since Helicobacter pylori was first cultured 10 years ago, there have been remarkable changes in our approach to the therapy of peptic ulcer disease. We now know that 90% of duodenal ulcer patients and 70% of all gastric ulcer patients are infected with H. pylori. Evidence is presented that the relapse rate of both duodenal and gastric ulcers can be substantially reduced if the bacterium is eradicated from the patient's stomach. Some of the anti-H. pylori eradication regimens currently available are discussed, with particular emphasis on the relative merits of standard triple therapy and an omeprazole/amoxycillin combination. PMID- 8341991 TI - Kinematic gait analysis in hemiplegic patients. AB - Temporal-distance variables of gait were investigated in 8 female and 23 male hemiplegic patients in order to assess the distribution of these variables according to functional ambulation category and to evaluate their validity. Video recording technique was used for obtaining the temporal-distance values. Velocity, step-time, stride length and stride length in relation to lower extremity length proved to be valuable measures in the gait analysis, while cadence, step-time and step-time differential values seemed to be less important. PMID- 8341992 TI - The influence of isometric hip adduction on quadriceps femoris activity. AB - In the treatment of muscle imbalances around the knee, hip adduction and the contraction of adductor magnus have been used to facilitate vastus medialis obliquus (VMO) to a greater extent than vastus lateralis (VL). This study was conducted to investigate the effectiveness of this technique. Hip adduction was superimposed onto the contraction of quadriceps femoris in a weight bearing (WB) and a non-weight bearing (NWB) position at three levels of hip adduction force. The muscle activity of VMO and VL was recorded using electromyography with the ratio of the recordings of VMO to VL used for comparison. The activity of VMO compared with VL was greater in WB than NWB without hip adduction. VMO activity increased relatively more than VL with the addition of each level of hip adduction in WB and only with maximal hip adduction in NWB. The results provide support for the use of this technique. PMID- 8341993 TI - Impact of knee extensor strength deficits on stair ascent performance in patients after medial meniscectomy. AB - After arthroscopic meniscectomy the relationship between the magnitude of knee extensor strength deficits and locomotor performance during stair ascent unloaded and when carrying a 22 kg load has been tested in 31 patients. The specific locomotor adaptations related to large strength deficits were also studied. The results indicate that large deficits were significantly associated to: 1) reduced activation of the knee extensor muscles (vastus medialis and lateralis) during the first double leg support and single leg support phases, and of the hip extensors (medial hamstrings) during the second double leg support of stair ascent, 2) overactivations of the hip extensors (gluteus maximus and medial hamstrings) during single leg support, and 3) longer cycle and step durations and lower cadences. Locomotor abnormalities in movements and muscle activations were generally found in patients with strength deficits greater than 25% while patients with smaller strength deficits (less than 25%) usually could climb stairs with normal performance. These results support the use of knee extensor strength measures to predict locomotor capacities, and also highlight the importance of postoperative knee strength rehabilitation. PMID- 8341994 TI - Lung volumes in tetraplegic patients according to cervical spinal cord injury level. AB - Fifty-six tetraplegic patients with motor complete lesions (Frankel A and B) underwent spirometric measurements more than 6 months after injury. The results were evaluated according to the level of transection of the cervical cord. A pronounced restrictive respiratory dysfunction was demonstrated in all patients. The expiratory reserve volume (ERV) was zero or markedly reduced in patients at all lesion levels. Systematic increases in both ERV and vital capacity (VC) were found with lower lesion level. The inspiratory capacity (IC) was reduced at all injury levels, but there were no systematic differences in IC between injury levels C4-C8. The total lung capacity (TLC) was reduced and the ratio residual volume/total lung capacity (RV/TLC) was increased in patients at all injury levels. The lung function of patients tested > 12 months after injury was not significantly different from the function in those tested 6-12 months after injury. A respiratory rehabilitation programme for tetraplegic patients should take into account the fact that the respiratory function, especially the forced expiration, is dependent upon injury level. PMID- 8341995 TI - Lymphoedema post-mastectomy: is elevation alone an effective treatment? AB - In an attempt to obtain information about the efficacy of arm elevation on the reduction of lymphoedema following mastectomy, a study on 33 patients was carried out in which both the control, contralateral and lymphoedematous arms were elevated for periods of 1 and 5 h. There were statistically significant (p < 0.05) reductions in the volumes of the control and lymphoedematous arms after 1 and 5 h of elevation. After 1 h of elevation, significantly more fluid was removed from the control arm (2.7%) than the lymphoedematous one (1.3%). At 5 h there was no significant difference in the volume of fluid removed from the control arm (3.3%) compared with the lymphoedematous one (3.1%). PMID- 8341996 TI - Rehabilitation after coronary bypass surgery: coping strategies predict metabolic improvement and return to work. AB - Thirty-six consecutive male patients who underwent coronary bypass surgery were investigated before and repeatedly up to 5 years after surgery. We followed the patients' physical capacity, dietary and exercise habits, mood, perception of health and return to work. Discriminant analysis identified four variables from the preoperative interview and the psychological tests which correctly classified 22 out of 24 patients into either metabolic responders--who were characterized by favourable changes in their lipoprotein profile, related to a successful clinical outcome--or non-responders. Responders were found to acknowledge subjective, emotional aspects of their situation whereas non-responders minimised their disease. Six preoperative variables successfully predicted the classification of all but one patient into full-time workers or not, one year after surgery. Full time workers were more frequent among minimizers. The results suggest that whereas minimising of disease is adaptive in a short-term perspective, acknowledgement may be successful in the long run. PMID- 8341997 TI - [Late sequelae in a group of children and adolescents treated for cancer between 1981 and 1986 in Switzerland]. AB - An ever-growing number of children with malignant diseases can today be cured and will have prolonged survival. Their quality of life, which can be altered by a substantial number of late effects of the disease or its treatment, is a prominent field of long-term assessment. In a cross-sectional study based on clinical and paraclinical parameters and covering 59 children and young adults treated between 1981 and 1986 for a childhood malignant disease, we investigated late effects in the long-term survivors. Late effects were found in 36 (61%) of these patients; their spectrum is wide, but most often affected are the CNS and the musculoskeletal system. Two thirds of the patients have mild or moderate and one third severe problems. The frequency of the late effects and the type of problem vary greatly according to the initial diagnosis; our results show a significant difference of severity according to the number of affected systems (p < 0.05). The results of our study match those of other similar reports and confirm the high frequency of late effects in survivors of pediatric cancer. A prospective study, assessing a large population of patients, is needed to determine the underlying causes and to develop primary and secondary prevention strategies. PMID- 8341998 TI - [Results of short-term tuberculosis therapy with isoniazid, rifampicin and pyrazinamide]. AB - Short-course chemotherapy of six-month duration with an initial combination of three drugs (isoniazid [H], rifampin [R] and pyrazinamide [Z]) is recommended as the treatment of choice in tuberculosis today. Use of fixed-combination tablet (Rifater) prevents prescription errors by physicians and selective intake by noncompliant patients. It should therefore assist in the prevention of emergence of drug resistance. In a controlled study at a chest hospital in Switzerland involving 261 patients with culture proven tuberculosis, the following two regimens were compared: 1) Six-month therapy (n = 128) with daily Rifater for two months, followed by H and R for four months. 2) Nine-month therapy (n = 133) with H and R daily for nine months, supplemented by ethambutol for the first two months. The two patient groups were comparable except for initial drug resistance (16% vs 8%, p < 0.05). Overall resistance to H was 10%. Five patients had initial resistance to two or more drugs. 227 patients were re-examined 1-8, and on average 4 years after therapy: four patients relapsed after 12, 20, 36 and 90 months. Two patients with initial drug resistance to H later developed resistance to R; both of these, as well as a third relapse patient, were cured with subsequent multi-drug therapy. Despite two and a half years of chemotherapy and repeated surgery, the fourth patient with initial resistance to H and R could not be cured. All relapse patients with initial drug resistance were randomized into the six-month therapy group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8341999 TI - [Mesenteric panniculitis]. AB - A 70-year-old patient with a 6 x 6 x 12 cm mass involving the mesentery root is discussed. The pseudotumorous infiltration was detected by ultrasound done because of nonspecific abdominal symptoms and weight loss. Laparoscopic biopsy confirmed the diagnosis of mesenteric panniculitis. The primary histologic criterion is infiltration of the mesenterium by foamy lipid-laden macrophages, clusters of lymphocytes and fibrosis. The majority of cases follow a benign course and need no therapy, but co-existence of lymphoma has been reported. There have been few cases where panniculitis with progressive fibrosis changed into retractile mesenteritis with shortening of the mesenterium and compression of mesenteric vessels with partial or complete intestinal obstruction or ischemia requiring surgery. Few reported cases of severe and progressive disease have been treated with prednisone and azathioprine or cyclophosphamide. PMID- 8342000 TI - [Are there antidepressants specially indicated in certain depressive disorders?]. AB - Treatment for depression has improved and several well tolerated antidepressants have been developed. The diagnosis is less important for the choice of treatment than the severity of the symptoms. Antidepressants are indicated if a depression is of at least moderate severity. For many years attempt has been made to find specific criteria for the choice of the "right" antidepressant. At present the scientific results do not allow unequivocal formulation of criteria for the differential indication of antidepressants. When treating patients we have nevertheless to decide which antidepressants to prescribe. Based on scientific results and long therapeutic experience, the author indicates which antidepressants may be more successful in which depression (retarded depression, agitated depression, delusional depression, suicidal ideas, anxiety, obsessive compulsive symptoms, eating disorders and atypical depression). PMID- 8342001 TI - [Vertigo and migraine]. AB - Vertigo consists of a variety of syndromes and can be due to many etiologies. One of these causes is migraine, which in our experience is often overlooked, although migrainous vertigo is well known in the literature. Vertigo in migraine can occur as aura or during the headache phase, or independent of the attacks as aura without headache. The aim of this retrospective study was to analyze cases with vertigo and migraine: 23 (8%) of 298 patients with migraine examined in a neurological outpatient department also had rotational vertigo. 48% of these patients had vertigo independent from typical migraine headache. Two types of vertigo were found: permanent vertigo, and vertigo with the characteristics of paroxysmal positional vertigo. 57% of the vertiginous attacks lasted hours, 26% even days, and 17% minutes. Most of the patients had several attacks of vertigo, some involving up to 30 episodes. To recognize migraine as a cause of vertigo has therapeutic implications. Most of our patients with vertigo and migraine showed a good response to antimigraine therapy. PMID- 8342002 TI - [Partial kidney resection in renal cell carcinoma]. AB - In 18 patients with renal cell carcinoma in anatomical or functional single kidneys, with limited renal function or bilateral tumors, partial renal resection was absolutely indicated to preserve renal function. In 17 patients with small peripheral tumors and intact contralateral kidney, partial renal resection was performed electively. One patient of each group died during postoperative care. During follow-up, 4 patients with absolute indication for partial renal resection showed progression of the disease. Three developed distant metastases, and in one patient local relapse with infiltration of the inferior cava vein occurred. These 4 patients had had a bilateral synchronous or asynchronous stage pT2 or pT3 renal cell carcinoma and died from the neoplasm within 10-36 months postoperatively. 13 of 18 patients with absolute indication remained tumorfree during a median follow up period of 57 months. Partial renal resection saved 15 of these 17 patients from dialysis. Sixteen of 17 patients in whom partial renal resection was performed electively remained tumorfree during a median follow-up period of 28 months. The results suggest that, given an absolute indication to prevent dialysis, partial renal resection should be performed whenever technically possible. In patients with small peripherally located tumors and intact contralateral kidney, partial renal resection as an elective procedure must be considered a genuine alternative to radical nephrectomy. PMID- 8342003 TI - [Villous adenoma of Vater's papilla. Problems in diagnosis and therapy]. AB - Adenomas of the ampulla of Vater are rare tumors which cause the same diagnostic problems as adenomas of the colon and rectum. From 1984 to 1991 we treated 5 patients with adenomas of the ampulla of Vater verified by endoscopy and biopsy. All 5 patients underwent transduodenal papillectomy and reimplantation of the common bile duct and pancreatic duct with intraoperative frozen section examination of the specimen. In 2 out of the 5 cases, the definitive diagnosis was invasive carcinoma undetected by frozen section examination. Both patients subsequently underwent partial duodenopancreatectomy with preservation of the pylorus. In one of our patients villous adenoma was detected six years after the insertion of a biliary endoprosthesis for alveolar echinococcus infiltrating the bifurcation of the hepatic ducts, a finding which raises the question as to an etiologic role of long-time biliary duct stenting. We discuss the diagnostic problems of the adenoma-carcinoma sequence and the therapeutic options. PMID- 8342004 TI - [Post-cholestatic hypercholeresis in a patient with malignant obstruction of the bile ducts]. AB - Increased choleresis of up to 4950 ml per day was observed after positioning of a PTCD in a patient with complete biliary obstruction due to a malignant tumor. Bile secretion could be temporarily reduced to 15% of the initial flow rate by intravenous administration of somatostatin. Simultaneously, the concentration of bile acids increased from 1.2 to 6.2 mmol/l, whereas the concentrations of electrolytes remained constant. Cholic acid had no influence on bile secretion. To safeguard the patient from excessive loss of fluid and electrolytes, the drained bile was reinfused into the duodenum via a PEG. PMID- 8342005 TI - [Malignant neuroleptic syndrome under metoclopramide and neuroleptics in anuria]. AB - A patient with myeloma nephropathy and acute, probably diclofenac-induced renal failure developed a neuroleptic malignant syndrome (NMS) during treatment with metoclopramide and neuroleptics. These drugs were withdrawn, symptomatic treatment of NMS was started and the patient was hemodialyzed because of uremia. During hemodialysis, the patient's condition improved dramatically and NMS did not recur during her further stay in the hospital. The temporal relationship between metoclopramide administration and the development of NMS, as well as the rapid reversal of NMS, suggest that NMS in this patient was caused by metoclopramide and not by neuroleptic drugs. Thus, metoclopramide should be used with caution in patients with renal failure and patients should be monitored closely for the development of neuroleptic malignant syndrome. Hemodialysis may be therapeutically effective in certain patients with metoclopramide-induced NMS. PMID- 8342006 TI - [Statistical deviations in high-performance athletes]. AB - Between 1978 and 1984, 1323 high level athletes were tested at the Sports sciences institute of the Swiss federal sports school. During these investigations, several characteristic variations of body statics were measured. Analysis of the pooled data reveal a link of statistical significance between certain sports and several abnormalities of lower limbs static. As it was a retrospective investigation, we cannot be sure of a causal relationship between the reported effects. Our principal aim however was to publish this somewhat extensive set of data, in view of the general dearth of such scientific results. In addition to the type of movement the athletes perform during their sports activity, it is the duration of the exertion which seems to be an important determinant for the presence of an increased number of static abnormalities in certain sports. Endurance running presents an elevated risk of developing both flat foot and splay foot. For football (soccer) and tennis players however, only a subnormal transverse foot arch appears frequently. Alpine skiers on the other hand have an increased risk of longitudinal foot arch insufficiency. The knowledge as to which abnormalities are increasingly present in a given sport is instrumental to enabling an early detection and prophylaxis of these ailments. PMID- 8342007 TI - [Neuroradiological studies in diving accidents]. AB - In case of a type II decompression sickness (with cerebrospinal injury), the decision on how to structure a prompt hyperbaric treatment rests on an anamnesis and the clinical investigation. In looking for an associated contingent barotrauma, one has to be satisfied with an X-ray of thorax and abdomen. The myelopathy which results from a decompression mishap with medullary involvement forms a very peculiar clinical entity defined by a fascicular injury at several levels. For several years now, clinical radiologists resort to a new medical imaging technique: Nuclear Magnetic Resonance (NMR-)Imaging. For the first time, this technique allows the imaging of intramedullary lesions due to a decompression accident. Other neuroradiological investigations (such as myelography, spinal tomodensitometry, medullary angiography, isotopic tests) are without merit for evaluating decompression accidents with medullary involvement. NMR-Imaging has the potential too, of revealing ischemic cerebral injuries, even if the clinical brain impairment is often silent and therefore overlooked. The role of NMR-Imaging for evaluating cerebrospinal aspect of decompression accidents is not yet finalized. However, NMR-Imaging will give without any doubt a boost to the pathophysiological knowledge of decompression mishaps. PMID- 8342008 TI - [Sports anthropological knowledge of relationships between individual hormone levels and anthropometric measuring values]. AB - As a tentative investigation of morpho-endocrinology, 92 male and 18 female long distance runners (ages 21 to 72) were measured according to the standard anthropological techniques. 66 anthropometric parameters, the colours of hair and eyes were recorded. Seven growth factors were derived by means of factor analysis. The levels of 13 hormones were measured and morphological and endocrinological parameters were compared by means of correlation coefficients. So human growth hormone showed correlations to macrosomia and hyperplastic robustness. Estradiol was primarily related to the more feminine features of men, but also to leanness and slenderness of women. Testosterone exhibited significant correlations to mesomorphy and masculinity of males and leptomorphism and strength of females. Both sexes with higher insulin levels seemed to be more fat. Thyroxine (T4) showed a relation to endomorphy and leptomorphism of face, whereas Triiodothyronine (T3) exhibited correlations to ectomorphy. Thyroid stimulating hormone (TSH) was paralleling mesomorphy of males and hyperplastic robustness of females. Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and Prolactin were related to microsomia and hypoplasia. The T4 levels of the dark haired athletes were significantly higher than the levels of the bright-haired. Several correlations between morphology and hormonal status have been shown, which may be interpreted as a permanent endocrine constitution paralleling the somatotypical body shape, outlasting growth. These correlations however should not be interpreted as causal, as further experimental studies are needed to ascertain such a link. PMID- 8342009 TI - [Why L-carnitine works in sports inspite of everything]. PMID- 8342010 TI - [Does L-carnitine really not work?]. PMID- 8342011 TI - Dental institute report. PMID- 8342012 TI - Dingell pursues AIDS patent 'cover-up'. PMID- 8342013 TI - Human growth hormone. French scientists may face charges over CJD outbreak. PMID- 8342014 TI - AZT patent. Court favors drug 'concept' over proof. PMID- 8342015 TI - Bacteria may provide access to the tsetse fly. PMID- 8342016 TI - Biomedicine in the age of imaging. PMID- 8342017 TI - OCT: images of coherence. PMID- 8342018 TI - Echo-planar MRI: learning to read minds. PMID- 8342019 TI - EEG + MRI: a sum greater than the parts. PMID- 8342020 TI - Transillumination: looking right through you. PMID- 8342021 TI - Direct colorimetric detection of a receptor-ligand interaction by a polymerized bilayer assembly. AB - Detection of receptor-ligand interactions is generally accomplished by indirect assays such as enzyme-linked immunosorbent assay. A direct colorimetric detection method based on a polydiacetylene bilayer assembled on glass microscope slides has been developed. The bilayer is composed of a self-assembled monolayer of octadecylsilane and a Langmuir-Blodgett monolayer of polydiacetylene. The polydiacetylene layer is functionalized with an analog of sialic acid, the receptor-specific ligand for the influenza virus hemagglutinin. The sialic acid ligand serves as a molecular recognition element and the conjugated polymer backbone signals binding at the surface by a chromatic transition. The color transition is readily visible to the naked eye as a blue to red color change and can be quantified by visible absorption spectroscopy. Direct colorimetric detection by polydiacetylene films offers new possibilities for diagnostic applications and screening for new drug candidates or binding ligands. PMID- 8342022 TI - Greater susceptibility to mutations in lagging strand of DNA replication in Escherichia coli than in leading strand. AB - Models of DNA replication in Escherichia coli involve an asymmetric DNA polymerase complex that replicates concurrently the leading and the lagging strands of double-stranded DNA. The effect of asymmetry on mutagenesis was tested with pairs of plasmids containing the unidirectional ColE1 origin of replication and a single lesion located in the leading or lagging strand. The lesion used was the covalent adduct that the chemical carcinogen N-2-acetylaminofluorene (AAF) forms with the C-8 position of guanine. Whether SOS was induced or not, mutations arose at about a 20-fold higher frequency when the AAF adduct was located in the lagging strand than when in the leading strand. PMID- 8342023 TI - Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. AB - A method was developed to clone, without the use of specific functional assays, complementary DNAs (cDNAs) that carry specific amino-terminal signal sequences, such as those encoding intercellular signal-transducing molecules and receptors. The vector used in this system directed the cell surface expression of interleukin-2 receptor fusion proteins when inserts with signal sequences were cloned in-frame with the correct orientation. An expression cDNA library was constructed from a bone marrow stromal cell line, which contained 5' portion enriched cDNAs (the average size was 400 base pairs). Two cDNAs that encoded putative cytokine molecules, stromal cell-derived factor-1 alpha (SDF-1 alpha) and SDF-1 beta, which belong to the intercrine-macrophage inflammatory protein superfamily, were cloned. PMID- 8342024 TI - Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin. AB - Structure-specific recognition proteins (SSRPs) bind to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. A yeast gene encoding an SSRP, designated IXR1, was cloned and sequenced. The Ixr1 protein, a member of the high mobility group-box protein family, bound specifically to DNA modified with cisplatin but not inactive platinum compounds. A yeast strain with an inactivated IXR1 gene was half as sensitive to cisplatin and accumulated one third as many platinum-DNA lesions after treatment with cisplatin as the parental strain. These findings suggest that SSRPs play a role in mediating the cytotoxicity of cisplatin. PMID- 8342025 TI - A detailed genetic map for the X chromosome of the malaria vector, Anopheles gambiae. AB - Anopheles gambiae, the primary vector of human malaria in Africa, is responsible for approximately a million deaths per year, mostly of children. Despite its significance in disease transmission, this mosquito has not been studied extensively by genetic or molecular techniques. To facilitate studies on this vector, a genetic map has been developed that covers the X chromosome at an average resolution of 2 centimorgans. This map has been integrated with the chromosome banding pattern and used to localize a recessive, sex-linked mutation (white eye) to within 1 centimorgan of flanking markers. PMID- 8342026 TI - Interaction of activated EGF receptors with coated pit adaptins. AB - The epidermal growth factor (EGF) receptor interacts with plasma membrane associated adapter proteins during endocytosis through coated pits. Almost 50 percent of the total pool of alpha-adaptins was coimmunoprecipitated with the EGF receptor when A-431 cells were treated with EGF at 37 degrees C, but not at 4 degrees C. Partial proteolysis of alpha-adaptin suggested that the amino-terminal domain is the region that associates with the EGF receptor. The extent of receptor-adaptin association was increased in cells depleted of potassium to block endocytosis. These data suggest that receptor-adaptin association occurs in intact cells before coated pits are fully assembled. PMID- 8342027 TI - Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and handedness. AB - A hemispheric asymmetry in the functional activation of the human motor cortex during contralateral (C) and ipsilateral (I) finger movements, especially in right-handed subjects, was documented with nuclear magnetic resonance imaging at high field strength (4 tesla). Whereas the right motor cortex was activated mostly during contralateral finger movements in both right-handed (C/I mean area of activation = 36.8) and left-handed (C/I = 29.9) subjects, the left motor cortex was activated substantially during ipsilateral movements in left-handed subjects (C/I = 5.4) and even more so in right-handed subjects (C/I = 1.3). PMID- 8342028 TI - The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter. AB - Mutations in the unc-17 gene of the nematode Caenorhabditis elegans produce deficits in neuromuscular function. This gene was cloned and complementary DNAs were sequenced. On the basis of sequence similarity to mammalian vesicular transporters of biogenic amines and of localization to synaptic vesicles of cholinergic neurons in C. elegans, unc-17 likely encodes the vesicular transporter of acetylcholine. Mutations that eliminated all unc-17 gene function were lethal, suggesting that the acetylcholine transporter is essential. Molecular analysis of unc-17 mutations will allow the correlation of specific parts of the gene (and the protein) with observed functional defects. The mutants will also be useful for the isolation of extragenic suppressors, which could identify genes encoding proteins that interact with UNC-17. PMID- 8342029 TI - Locating the catalytic water molecule in serine proteases. PMID- 8342030 TI - Bioinorganic chemistry. PMID- 8342031 TI - The missing AIDS science. PMID- 8342032 TI - Marine lab weathers a storm. PMID- 8342033 TI - PCR enzyme. The more you use, the cheaper it gets. PMID- 8342034 TI - French AIDS tests get the hook. PMID- 8342035 TI - Where are 'new' diseases born? PMID- 8342036 TI - Australian pest control by virus causes concern. PMID- 8342037 TI - Bioinorganic chemistry: a maturing frontier. PMID- 8342038 TI - Transition metals in control of gene expression. AB - Metalloproteins play structural and catalytic roles in gene expression. The metalloregulatory proteins are a subclass that exerts metal-responsive control of genes involved in respiration, metabolism, and metal-specific homeostasis or stress-response systems, such as iron uptake and storage, copper efflux, and mercury detoxification. Two allosteric mechanisms for control of gene expression were first discovered in metalloregulatory systems: an iron-responsive translational control mechanism for ferritin production and a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes. These otherwise unrelated mechanisms give rise to a rapid physiological response when metal ion concentrations exceed a dangerous threshold. Molecular recognition in these allosteric metal ion receptors is achieved through atypical coordination geometries, cluster formation, or complexes with prosthetic groups, such as sulfide and heme. Thus, many of the inorganic assemblies that otherwise buttress the structure of biopolymers or catalyze substrate transformation in active sites of enzymes have also been adapted to serve sensor functions in the metalloregulatory proteins. Mechanistic studies of these metal-sensor protein interactions are providing new insights into fundamental aspects of inorganic chemistry, molecular biology, and cellular physiology. PMID- 8342039 TI - Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. AB - Cytochrome P450BM-3, a bacterial fatty acid monoxygenase, resembles the eukaryotic microsomal P450's and their flavoprotein reductase in primary structure and function. The three-dimensional structure of the hemoprotein domain of P450BM-3 was determined by x-ray diffraction and refined to an R factor of 16.9 percent at 2.0 angstrom resolution. The structure consists of an alph and a beta domain. The active site heme is accessible through a long hydrophobic channel formed primarily by the beta domain and the B' and F helices of the alpha domain. The two molecules in the asymmetric unit differ in conformation around the substrate binding pocket. Substantial differences between P450BM-3 and P450cam, the only other P450 structure available, are observed around the substrate binding pocket and the regions important for redox partner binding. A general mechanism for proton transfer in P450's is also proposed. PMID- 8342040 TI - Dialkylglycine decarboxylase structure: bifunctional active site and alkali metal sites. AB - The structure of the bifunctional, pyridoxal phosphate-dependent enzyme dialkylglycine decarboxylase was determined to 2.1-angstrom resolution. Model building suggests that a single cleavage site catalyzes both decarboxylation and transamination by maximizing stereoelectronic advantages and providing electrostatic and general base catalysis. The enzyme contains two binding sites for alkali metal ions. One is located near the active site and accounts for the dependence of activity on potassium ions. The other is located at the carboxyl terminus of an alpha helix. These sites help show how proteins can specifically bind alkali metals and how these ions can exert functional effects. PMID- 8342041 TI - DNA melting on yeast RNA polymerase II promoters. AB - Transcription-dependent DNA melting on the yeast GAL1 and GAL10 promoters was found to be more closely correlated with the TATA box than the transcription start site. On both these genes, melting begins about 20 base pairs downstream of the TATA box. Physical and genetic analyses suggest that RNA polymerase II associates with this region. Thus, the distance between promoter melting and the TATA box in yeast may be similar to that in higher eukaryotes, even though transcription initiates in a region about 10 to 90 base pairs farther downstream in yeast. PMID- 8342042 TI - Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. AB - Major histocompatibility complex (MHC) class I molecules present peptides derived from nuclear and cytosolic proteins to CD8+ T cells. These peptides are translocated into the lumen of the endoplasmic reticulum (ER) to associate with class I molecules. Two MHC-encoded putative transporter proteins, TAP1 and TAP2, are required for efficient assembly of class I molecules and presentation of endogenous peptides. Expression of TAP1 and TAP2 in a mutant cell line resulted in the delivery of an 11-amino acid oligomer model peptide to the ER. Peptide translocation depended on the sequence of the peptide, was adenosine triphosphate (ATP)-dependent, required ATP hydrolysis, and was inhibited in a concentration dependent manner. PMID- 8342043 TI - Heat shock (stress) proteins and autoimmunity in rheumatic diseases. AB - The rheumatic diseases (RDs) are characterized by acute and chronic inflammation, and autoimmunity plays a major role in their pathogenesis. RDs are for the most part of unknown etiology, but recent evidence indicates that heat shock or stress proteins (HSPs) may have an important role in the etiology/pathogenesis of RDs. HSPs are produced by prokaryotic and eukaryotic cells and are grouped according to molecular weight. Phylogenetically, HSPs are very old and are remarkably conserved molecules in evolution from bacteria to humans. HSPs are induced by a variety of cellular stresses in addition to heat; cognates are expressed constitutively and are essential in a number of normal functions. Some HSPs serve as molecular chaperones, the latter defined as proteins that mediate folding of other polypeptides and either promote their assembly into oligomeric structures or disassemble the final product. Conservation of structure and function of many HSPs may provide a link between immunity to infection and the autoimmune features of RDs. Evidence is reviewed from clinical and laboratory observations that diverse microbial agents, including viruses, bacteria, and parasites, may have putative roles in the development and pathogenesis of some RDs. HSPs also are discussed in relation to the major histocompatibility complex, HLA antigens, and disease associations and how they may alter the balance between tolerance and autoimmunity. Studies are reviewed that are supportive or nonsupportive of the concept of microbial infection associated with autoimmunity; individuals first react to microbial immunizations or infections with enhanced cellular/humoral responses to the agent's HSPs. With the enhanced immune response, cross reactivity may occur with an HSP of the stressed host because of structural similarities to the microbial HSP. If all of these events occur, the host's homologous HSP or stressed cells now become true autoantigen(s). This sequence has implications for the etiology of immune-mediated RDs, the concept of epitope sharing, and the accompanying autoimmunity. A recurring theme emphasized in some reports to understand better the role of HSPs in autoimmunity is the need to select patients with early-onset disease. A minor subpopulation of T lymphocytes express a CD3-associated T-cell receptor (TCR) heterodimer composed of gamma and delta polypeptide chains. The gamma delta + T cells have several unique features. When analyzed by the polymerase chain reaction, lymphocytes with TCR-gamma delta appear to reflect the polyclonal expansion of preexisting gamma delta clones. They are found in peripheral lymphoid tissue in very low percentage (< 5%) but may represent the majority of T cells within epithelial tissue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8342044 TI - Corticosteroid-induced osteoporosis. AB - Corticosteroid-induced osteoporosis is a major problem faced by rheumatologists, with up to 50% of patients at increased risk for vertebral fractures. Our current understanding of the pathophysiology of corticosteroid-induced osteoporosis suggests two basic problems: a reduction in bone formation and an increase in bone resorption leading to an overall reduction in bone mass. Adequate calcium and vitamin D intake, calcitonin, hormone-replacement therapy, and thiazide diuretics are of benefit in preventing corticosteroid-induced bone loss. Other therapies such as the bisphosphonates, fluoride, and anabolic steroids should be considered when fractures occur or ongoing bone loss is evident. A review of the literature outlining the pathophysiology, clinical features, assessment, and treatment is presented. PMID- 8342045 TI - Antilipoprotein antibodies in rheumatoid arthritis. AB - Antibodies against very low-density lipoproteins and low-density lipoproteins (aLA) were found in 26 of 69 (38%) patients with active rheumatoid arthritis (RA) but not in any control subjects (ie, 40 patients with psoriatic arthritis, 21 patients with osteoarthritis, and 65 healthy blood donors). In 21 RA patients (30%), lipoproteins were found in the dissociated components of circulating immune complexes. RA patients with aLA had significantly decreased cholesterol levels in all lipoprotein fractions and total serum lipids, while serum triglycerides were significantly increased compared with RA patients without aLA. Anticardiolipin antibodies as measured by the Venereal Disease Research Laboratory test were not found in any subject in this study. These findings suggest a possible autoimmune origin of dyslipoproteinemia in some patients with active RA. PMID- 8342046 TI - Lymphatic disorders in rheumatoid arthritis. AB - Lymphedema is a rare complication of rheumatoid arthritis (RA). Diagnosis is clinical: long-standing, painful swelling of a whole limb in association with RA. Cases described in the literature are predominantly of the upper limbs, sometimes bilateral. Diagnosis can be confirmed by biopsy of lymph nodes, lymphography, or preferably lymphoscintigraphy. The etiology of the edema is unknown. Mechanical obstruction and lymphangitis have been suggested. Pharmacological and surgical treatment of the edema have been disappointing, and treatment of the underlying RA does not improve the lymphedema. Physical treatment of the affected limb, such as massage, manual drainage techniques, light compression bandaging, and exercise, has been moderately effective. PMID- 8342047 TI - Autoimmunity and selected environmental factors of disease induction. AB - Autoimmune diseases may be induced by physical and/or chemical environmental factors. A review of the available literature on mercuric chloride, iodine, silicone, anilides, L-tryptophan, vinyl chloride, and canavanine suggests three general mechanisms by which they may induce disease. First, oxidative damage probably is a frequent process involved in disease induction and pathogenesis. Second, certain compounds also may generate antigen-specific immune responses that could then cross-react with self-tissues. Other xenobiotics might bind to self-tissues and increase self-tissue immunogenicity. Third, physical and chemical agents may also modulate the immune system. Finally, in response to controversies surrounding the influence of human activities on global climate changes, the immunosuppressive effects of ozone and ultraviolet radiation are discussed. PMID- 8342048 TI - Reactive arthritis associated with Clostridium difficile pseudomembranous colitis. AB - Reactive arthritis is associated with several gastrointestinal pathogens, particularly Shigella, Salmonella, Campylobacter, and Yersinia. Another, less well recognized bowel infection leading to reactive arthritis is pseudomembranous colitis, caused by Clostridium difficile. An illustrative case is presented, and the clinical features and characteristics of all reported patients with this association are reviewed. The pathogenesis of the reactive arthritis seems to be related to an immunological response in joints and other tissues against bacterial antigens, which gain access to the systemic circulation through increased intestinal permeability. Therapy with nonspecific antiinflammatory drugs, anticlostridial agents, or a combination of the above is effective. Despite the possibility of persistent articular involvement after gastrointestinal symptoms have subsided, the long-term prognosis seems to be excellent. PMID- 8342049 TI - Osteoarthritis and hyaluronan--palliative or disease-modifying treatment? PMID- 8342050 TI - The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep. I. Gait analysis and radiological and morphological studies. AB - Using a model of early osteoarthritis (OA) induced in ovine joints by medial meniscectomy, the intraarticular effects of two hyaluronic acid (HA) preparations (AHA and DHA) were investigated. DHA was an HA preparation with an average molecular weight (MW) of approximately 2.0 x 10(6) d, and AHA had a MW of approximately 8 x 10(5) d. Animals (n = 5) were injected intraarticularly with 1 mL (10 mg/mL) of either HA preparation once a week for 5 weeks beginning 16 weeks after initiation of arthropathy. Meniscectomized, saline (1.0 mL)-injected animals (n = 5) and nonoperated sheep (n = 5) were used for controls. Force-plate analysis of gait and radiographic changes in joints were evaluated in these groups before and after intraarticular treatment. At necropsy, cartilage gross morphology, osteophyte development, and cartilage histopathology were examined. Meniscectomized joints were characterized by erosions and fissuring of cartilage of the medial compartment with areas of decreased matrix staining for proteoglycans. Osteophytes were present at the medial joint margins. Saline treated meniscectomized animals showed reduced loading of the operated limb using the force plate. Force-plate analysis of walking animals before and after treatment with either AHA or DHA indicated some normalization of joint loading. However, osteophyte scores for meniscectomized joints injected with AHA and DHA were higher after treatment than those of the corresponding saline-treated group. Although the gross cartilage damage was lower than in saline-treated controls for both the HA-treated groups, the histological scores did not support this conclusion. Indeed, the tibial score for the DHA group was higher than for the AHA group (P < .05). These studies confirmed previous reports that meniscectomy of sheep stifle (knee) joints resulted in matrix changes similar to those described for early OA in humans. Both HA preparations appeared to improve gait, suggesting decreased lameness. Increased joint loading associated with gait improvement may account for the higher osteophyte scores in the treated groups. However, cartilage damage with DHA was found to be higher than when the lower-MW HA preparation (AHA) was used. PMID- 8342051 TI - The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep. II. Cartilage composition and proteoglycan metabolism. AB - A model of early osteoarthritis (OA) induced in ovine joints by medial meniscectomy was used to study the effects of two hyaluronan (HA) preparations (AHA and DHA) on cartilage composition and proteoglycan (PG) metabolism. DHA was an HA preparation with an average molecular weight (MW) of approximately 2.0 x 10(6) d, and AHA had an MW of approximately 8.0 x 10(5) d. Both preparations were administered intraarticularly once a week for 5 weeks starting 16 weeks after meniscectomy, and animals (n = 5) were killed 5 weeks after the last injection. Meniscectomized, saline-injected (n = 5) and nonoperated (n = 5) animals were used for controls. At necropsy, 3-mm-diameter full-depth cartilage plugs were sampled under sterile conditions from specific locations on the medial and lateral femoral condyles, tibial plateaus, patella, and trochlear groove. The cartilage plugs were cultured in Hams-F12 medium supplemented with 10% fetal calf serum for 24 hours, then for a further 48 hours in the presence of H2(35)SO4 to determine the biosynthesis of PGs. The percentage of 35S-PGs and sulfated glycosaminoglycans released into the media was also ascertained. The cartilage adjacent to the plugs was analyzed for collagen and proteoglycan content and differential extractability with guanidine hydrochloride (GuHCl) solutions. The extractability of PGs with 0.4 mol/L GuHCl (nondissociative conditions) was lower from the medial femoral cartilages of the DHA-treated group than from the corresponding saline-treated group. In contrast, the release of 35S-PGs from the tibial cartilages of the DHA-treated animals was higher than in the saline treated group. The biosynthesis of 35S-PGs, determined in vitro, for cartilage derived from the medial compartment was generally lower than for the lateral regions of the meniscectomized joints. The biosynthetic activity was further reduced in joints injected with the two HA preparations, but DHA reduced 35SO4 incorporation into PGs more than AHA. It was concluded that reduced biosynthesis of 35S-PGs and secretion into media was a consequence of increased loading of joints in the HA-treated animals rather than a direct effect of these preparations on chondrocyte metabolism. PMID- 8342052 TI - Effects of intraarticular hyaluronan on matrix changes induced in the lateral meniscus by total medial meniscectomy and exercise. AB - Total medial meniscectomy was performed in 12 adult merino sheep. Immediately after surgery, 8 animals received high-molecular-weight hyaluronan (HA) (1 mL, 10 mg/mL) and 4 were given sterile saline (1 mL) intraarticularly. Injections were given for 5 more weeks. In week 3 an exercise program, consisting of walking 24 km/wk, was initiated. This program was continued until the animals were killed at week 26 postmeniscectomy. At necropsy the lateral menisci were removed and divided into three concentric zones--inner, middle, and outer. Powdered aliquots of tissues from each zone were analyzed for collagen and hexuronate contents using colormetric methods. The glycosaminoglycans (GAGs)--chondroitin-O-sulfate (C-O-S), chondroitin-4-sulfate (C-4-S), chondroitin-6-sulfate (C-6-S), and dermatan sulfate (DS)--were determined using a high-performance liquid chromatography method. The lateral menisci from the joints of animals injected with HA showed higher hexuronate and GAG levels than those of controls. This increase was mainly due to C-6-S, which had highest levels in the inner and middle meniscal zones. In addition, dermatan sulfate levels increased significantly in the middle and outer zones of the lateral menisci compared with the same zones of the meniscus from the saline-treated group. Collagen and C-O-S levels were not statistically different from those of controls. These data suggest that intraarticular administration of high-molecular-weight HA immediately after open total medial meniscectomy may help preserve the proteoglycans in the lateral meniscus remaining in the joint. PMID- 8342053 TI - The kinetics of hyaluronan in normal and acutely inflamed synovial joints: observations with experimental arthritis in sheep. AB - The metabolic half-life of hyaluronan (HA) in synovial fluid was estimated in sheep from the rate of appearance of 3H2O in plasma after injection of highly polymerized labeled HA. This material is substituted with 3H in its acetyl group and is rapidly and almost completely degraded in sheep and other species to yield 3H2O. Previously sensitized sheep were studied before and after induction of acute monoarticular arthritis by intraarticular challenge with type II collagen. In both circumstances 3H was released from the joint in a monophasic exponential pattern and appeared in plasma only as 3H2O. Before challenge, the mean metabolic half-life of [3H]HA was 20.8 hours (range, 15.8 to 27.9 hours, n = 5); an estimate in a single unsensitized sheep (27.0 hours) fell within this range. After challenge, swelling occurred around the joint without frankly increased synovial fluid. The mean half-life fell to 11.5 hours (range, 9.0 to 16.8 hours), with a corresponding increase in mean fractional turnover from 3.5%/h to 6.3%/h; an increased amount of the label was also retained within the peripheral tissues. It is concluded that a relatively mild acute inflammation can induce major changes in the metabolic turnover of synovial HA without the development of gross effusions. In the course of this study, mean synovial fluid volume in the normal sheep hock joint was estimated to be 1.54 mL; the concentration and content of HA were 0.54 mg/mL and 0.84 mg, respectively. These data add to other evidence that the volume and HA content of normal synovial fluid vary widely in different joints and species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342054 TI - [Quality assurance in trauma surgery--what does the TRISS method offer ?]. AB - The TRISS method offers a standard approach for evaluating the outcome of trauma care. Based on the data of more than 150,000 patients, TRISS offers a method of calculating the individual probability of survival of trauma patients. The calculation is based on anatomical, physiological data and the age of the patient. The basic scores for using TRISS are the Revised Trauma Score and the Injury Severity Score. Recent analyses demonstrate for blunt trauma patients a sensitivity of 60.9% and a specificity of 99.2%. What does TRISS offer in comparison to other trauma scores? TRISS offers a valid approach for the screening of trauma patients regarding unexpected survival/death. Based on the largest database of trauma patients, TRISS represents a method of maintaining quality assurance for prehospital and hospital trauma patient care; it also allows comparison with international standards of trauma care. PMID- 8342055 TI - [Primary management of polytrauma. Comparison of a German and American air rescue unit]. AB - Hospital-based helicopter services from German and American university-affiliated trauma centers were reviewed. All multitrauma patients transported via helicopter from the scene of the accident to the trauma center during a 1-year period were included. The patients were comparable regarding mechanism of injury, age, flight times, mean ISS, ISS distribution, and number of severe injuries per body region (patients with AIS > 3 for head, thorax and abdomen). Overall mortality for the German system was 21/221 (9.5%) and 21/186 (11.3%) for the American system (not significant). Survivor-based TRISS analysis yielded Z-statistics of +2.459 for the German, and +1.049 for the American system. There were 9 unexpected survivors (Ps < 0.5) in the German, 6 in the American system. There was a significant higher (P < 0.01) number of early deaths (< 6 h) in the American population (12, ISS 56) than in the German (4, ISS 64). Analysis of the prehospital data demonstrated significant differences in the mean volume of IV fluids infused: 1800 cc German, 825 cc American (P < 0.05); rate of intubation: 82/221 (37.1%) German, 24/186 (13.4%) American (P < 0.001); and thoracic decompressions: 20/221 (9.1%) German, 1/186 (0.5%) American (P < 0.001). Pre-hospital care in the German system is directed on-scene by a trauma surgeon member of the flight crew, compared to a nurse/paramedic team with remote medical control in the American system. Compared to an American trauma system, the German system demonstrates improved overall outcome as measured by survivor-based TRISS Z-statistics. More favorable German Z-statistics are in part related to fewer early deaths.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342056 TI - [Biochemical wound monitoring. PMN elastase in different healing stages after trauma surgery-orthopedic interventions]. AB - Laboratory parameters are of proven value in the diagnosis of early postsurgical infections, since clinical aspects cannot always be clearly defined. Neutrophil granulocytes (PMN) are major inflammatory cells taking effect following ingestion and degradation of foreign material, such as bacteria and cell debris, for example after mechanical trauma. In patients who had undergone surgery we monitored the course of plasma PMN elastase in uncomplicated wound healing (n = 22), in uncomplicated wound healing associated with secondary infections (n = 6), and in defective wound healing (manifestation of a bacterial wound infection: n = 3; wound infection already manifest at the time of entry on study: n = 11). Surgical trauma was accompanied by an increase in PMN elastase and C-reactive protein (CRP) in all patients studied, reaching a maximum within the first 3 postsurgical days. When a bacterial wound infection became manifest during the course of healing there was a highly significant difference on the 4th postsurgical day (p < 0.01) compared with the group with uncomplicated healing. Since PMN elastase can now be determined automatically with an autoanalyser and a commercial kit and its discriminatory time point is as soon as 4-5 days after surgery, it is suggested that this marker should be determined routinely together with CRP in traumatology. PMID- 8342057 TI - [Severe parachuting accident. Analysis of 122 cases]. AB - Based on a population of 122 severely injured patients the causes of paragliding accidents and the patterns of injury are analyzed. A questionnaire is used to establish a sport-specific profile for the paragliding pilot. The lower limbs (55.7%) and the lower parts of the spine (45.9%) are the most frequently injured parts of the body. There is a high risk of multiple injuries after a single accident because of the tremendous axial power. The standard of equipment is good in over 90% of the cases. Insufficient training and failure to take account of geographical and meteorological conditions are the main determinants of accidents sustained by paragliders, most of whom are young. Nevertheless, 80% of our patients want to continue paragliding. Finally some advice is given on how to prevent paragliding accidents and injuries. PMID- 8342058 TI - [Long-term results of surgical management of patellar fractures]. AB - Between 1973 and 1989, 129 patients with 135 fractures of the patella were treated operatively. More than two-thirds of these patients were younger than 40 years at the time of the accident. The main cause of trauma was a traffic accident in 65.9%. Sixty patients had polytraumata. There were 74 comminuted, 28 transverse, 17 starlike, 10 longitudinal and 6 fractures with one large fragment. Eighty-two patients with 85 fractures were followed up after 8.4 years on average (1.2-16.3 years). The overall results were excellent or good in 64.7%, fair in 18.8% and poor in 16.5%. The best results were seen in transverse fractures after modified tension-band wiring using two longitudinal K wires, and in longitudinal fractures applying screws. Sixty-three percent of the fair and poor results were seen after osteosynthesis of comminuted fractures. In these cases primarily partial or complete patellectomy seems to be indicated instead of just insufficient reconstruction of the retropatellar face. Early functional physiotherapy is very important for all kinds of patellar fractures to gain full range of motion. PMID- 8342059 TI - [Follow-up and prognosis of neurologic sequelae of pelvic ring fractures with involvement of the sacrum and/or the iliosacral joint]. AB - The extent of neurological lesions following an injury of the pelvic ring is often not initially recognized, as interest is then focused on the treatment of the pelvic ring fracture. Once the fracture has healed, the patient suffers from the sequelae of the neurological injury. Our series of 323 pelvic ring injuries includes 161 sacral fractures and 12 complete disruptions of the sacroiliac joint. Twenty-three patients sustained an injury of the lumbosacral plexus, and 20 patients were examined retrospectively. The different parts of the lumbosacral plexus showed variable recovery potential. An important or complete recovery was noted in 8 of 9 patients suffering from a motor deficit of the lumbar plexus, the obturator nerve, the superior gluteal nerve or the inferior gluteal nerve. Four out of 8 patients with a motor deficit of the sacral plexus had an important or complete improvement. In contrast to these results was the poor recovery of lesions of the lumbosacral trunk. Eight out of 11 patients showed no or only minor recovery, although the pelvic ring was stabilized by operative means in 9 patients. In 2 patients the lumbosacral trunk was directly decompressed by a dorsal approach. In both cases the recovery was complete. In 6 patients the sphincter function was damaged. Recovery was dependent on the localization of the sacral fracture. If the fracture traversed the sacral canal, no neurological improvement was noted. PMID- 8342060 TI - [Case histories of therapy of traumatic knee joint dislocation]. AB - The records of eight patients with traumatic knee dislocation and operative treatment in 1981-1991 were reviewed. In this retrospective study the average follow-up was 6 years and indicated good results concerning stability and functional use of the knee. The vascular complications, especially the ischemic syndrome are associated with an emergency situation that requires immediate reduction. PMID- 8342061 TI - [Interlocking nailing of the humerus]. AB - Within a 3-year period a total of 42 humeral fractures were treated. Nineteen of these were operated on with the Seidel intramullary interlocking nail. Most of the fractures could be classified into group A (AO classification); three type B and four type C fractures occurred. Two patients had pathological fractures due to bone metastases. Mean hospital inpatient treatment was 24 days. Besides two infections seven system-specific complications occurred. A discrepancy between the diameter of the nail and the width of medullary cavity was the reason in one case for an additional fracture and in another case for nonunion because of loosening of the nail tip in the distal fragment. Three further intraoperative fractures occurred during impaction of the nail, the reasons are also device specific and are carefully analyzed. In two cases we were forced to remove the nail because of subacromial impingement due to an overranging proximal nail end. Finally, a normal intraoperative and postoperative course with good functional results could only be observed in approximately half the cases. Thus, our initial optimism with respect to the outstanding theoretical concept was dampened, so that the interlocking humerus nail is now just applied in pathological shaft fractures. PMID- 8342062 TI - [Reconstruction of foot arteries after injury in arterial occlusive disease]. AB - At the Maribor Teaching Hospital two elderly with progressive atherosclerotic disease below the knee were treated between 1986-1992 for open fracture of ankle joint and pedal arterial trauma. The only patent atherosclerotic vessel (dorsal artery of the foot) that was disrupted was reconstructed in both cases by interposition of a part of the great and small saphenous vein in one case each. A termino-terminal anastomosis with a long, triangular patch was used, fixed with interrupted sutures. The fractures were stabilized with external fixators. Both extremities were saved. PMID- 8342063 TI - [Experiences with closed irrigation-suction drainage and simultaneous administration of an antiseptic]. AB - In 47 patients a closed instillation drainage system was used with concomitant systemic antibiotic therapy. The schedule was strictly followed and is described in detail in the text. Prerequisites for a successful therapy are thorough surgical debridement, good coverage with soft tissue and a very careful skin closure. We propose a shortened duration of instillation of 3 to a maximum of 5 days. The Draintec suction pumps now used evidently create less problems than the classic pumps. During a mean follow-up of 3 years a definite recurrence was observed in two cases and a possible recurrence in one. In view of these results we consider this mode of treatment is still valid. Lavasept was added as an antiseptic drug in three quarters of the cases and was tolerated well. In view of the low rate of recurrence in all cases its potential cannot yet be fully estimated. We recommend the instillation-drainage system for use in thigh, upper arm and pelvic areas in the hands of a fully cooperating management team with some experience in the application of instillation-drainage systems. PMID- 8342064 TI - Immunotherapy of lung cancer. AB - Review of the literature on immunotherapies in lung cancer provides hope that an impact on the natural history of this disease can be achieved. Although the various trials of adjuvant nonspecific immunostimulation with BCG, levamisole, and C parvum are not sufficiently detailed to permit meta-analysis, in aggregate the data suggest a slight improvement in disease-free survival for treated patients. Perhaps these adjuvants combined with more immunogenic TAAs could be formulated into a vaccine that would be effective in preventing recurrence of lung cancer after surgical excision. Ongoing research in molecular technology may provide adequate quantities of such products so that this hypothesis can be tested in appropriate patient populations. PMID- 8342065 TI - Biological markers in smoking cessation treatment. PMID- 8342066 TI - Potential application of gene therapy to lung cancer. PMID- 8342067 TI - Early detection of lung cancer. PMID- 8342068 TI - Lung cancer: recent changes and expectations of improvements. PMID- 8342069 TI - Preparative Regimens in Bone Marrow Transplantation. Proceedings of a symposium. Anaheim, California, December 4, 1992. PMID- 8342070 TI - The development of busulfan/cyclophosphamide preparative regimens. AB - Bone marrow transplantation (BMT) preparative regimens consisting of busulfan (Bu) and cyclophosphamide (Cy) were developed as an alternative to preparative regimens based on total body irradiation (TBI). Animal studies demonstrated that Bu had a high level of myeloablative and antileukemic activity, but little immunosuppressive effect. In contrast, Cy was sufficiently immunosuppressive to allow allogeneic marrow engraftment in animal systems. In both animals and humans, the combination of Bu and Cy results in effective eradication of the host's bone marrow and suppression of the immune response, thus allowing engraftment by either allogeneic or autologous marrow. A number of BMT preparative regimens have been developed for use in leukemic patients. These regimens differ primarily in the myeloablative agent used (Bu or TBI) and the dose of Cy. Although few comparative studies have been conducted, BuCy regimens appear to be similar in efficacy to those containing Cy and TBI. In addition to its use in leukemic patients, BuCy BMT preparative regimens also have been used in patients with nonmalignant lymphohematopoietic disorders or other malignant diseases. PMID- 8342071 TI - Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. AB - High-dose busulfan is an important component of many bone marrow transplantation (BMT) preparative regimens. The dose-limiting toxicity of busulfan in BMT regimens is hepatic veno-occlusive disease (VOD), which occurs in approximately 20% to 40% of patients. We used a gas chromatography-electron capture detection assay and pharmacokinetic models to examine busulfan disposition in adults and children. Marked interpatient and intrapatient variability in busulfan disposition was observed in both patient populations. Part of the intrapatient variation appeared to be due to circadian changes in busulfan disposition. We also used gas chromatography-electron capture detection and pharmacokinetic models to assess whether excessive exposure to busulfan correlates with an increased risk of VOD. The area under the curve of time versus concentration (AUC) after the first dose of busulfan was measured in patients receiving a 16 dose course of busulfan as part of a BMT preparative regimen. In 27 patients who showed high AUCs (> 1,500 mumol.min/L) after the first dose, the fifth through 16th doses of busulfan were decreased. Patients with high AUCs who did not receive dose adjustments had a 75% incidence of VOD. The incidence of VOD was only 18% in patients with high AUCs whose dose was adjusted on the basis of therapeutic monitoring. 5% for those not needing adjustment. These studies suggest that therapeutic monitoring can play an important role in decreasing the toxicity of BMT preparative regimens. Therapeutic monitoring also may improve treatment efficacy by identifying patients who are not receiving adequate drug exposure. PMID- 8342072 TI - Treatment of chronic myelogenous leukemia with allogeneic bone marrow transplantation after preparation with busulfan and cyclophosphamide (BuCy2): an update. AB - Allogeneic bone marrow transplantation (BMT) has been shown to result in long term disease-free survival in patients with leukemia. However, the utility of this treatment approach is limited by treatment-related morbidity and mortality. We present an update of a study in which a BMT preparative regimen consisting of a 4-day course of busulfan and a 2-day course of cyclophosphamide (BuCy2) was used in patients with chronic myelogenous leukemia. Patient survival depended on disease stage, with a 58% survival rate for patients in first chronic phase, 41% for those in accelerated phase, and 25% for those in the blast transformation stage. There was a significant difference in patient survival between those who received transplants within 1 year of diagnosis and those who received transplants more than 1 year after diagnosis (70% v 40%). This difference appeared to be due to the extent of previous exposure to busulfan. The overall mortality rate in this study was 46%. We conclude that the BuCy2 preparative regimen is similar in effectiveness to regimens that include total body irradiation and results in comparable levels of transplant-related mortality. Our results strongly indicate that patients with chronic myelogenous leukemia who receive BMT within the first year after diagnosis have a significantly better clinical outcome than those who receive BMT later in the course of the disease. PMID- 8342073 TI - The influence of total dose, fractionation, dose rate, and distribution of total body irradiation on bone marrow transplantation. AB - Total body irradiation (TBI) is a common component of many preparative regimens used prior to bone marrow transplantation. The biologic effects of TBI are influenced by a number of factors, including total dose, dose fractionation, dose rate, and dose distribution. Higher doses of TBI result in greater antileukemic activity, but this effect may be offset by concomitant increases in treatment related toxicities. Increased doses of TBI also produce a greater degree of immunosuppression. Fractionated TBI results in decreased late toxicities and immunosuppressive effects when compared with single-dose TBI, yet the extent of marrow ablation seems to be similar. For both single-dose and fractionated TBI, higher dose rates produce increased treatment-related toxicities. Dose rates also may affect marrow ablation and immunosuppression. By targeting radiation to leukemic or immunocompetent cells, alterations in dose distribution have the potential to significantly improve the clinical benefits of TBI. Directed external beam irradiation is one approach to achieving the goal of targeted therapy. Other approaches involve the conjugation of radionuclides to antibodies that recognize specific cell-surface antigens or to aminophosphonic acid compounds that bind to bone. Such specific targeting of radiation could lead to significant increases in the intensity of therapy without resulting in greater treatment-related toxicities. PMID- 8342074 TI - Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2). AB - The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities. PMID- 8342075 TI - Busulfan plus etoposide as a preparative regimen for autologous bone marrow transplantation for acute myelogenous leukemia: an update. AB - We have used a new preparative regimen prior to autologous bone marrow transplantation in patients in remission of acute myelogenous leukemia (AML). Sixty-two patients were treated with preparative chemotherapy consisting of 1 mg/kg of busulfan every 6 hours for 4 days (total dose 16 mg/kg) on days -7 to -4 followed by an intravenous infusion of 60 mg/kg of etoposide on day -3. Autologous bone marrow that had been purged with 4-hydroperoxycyclophosphamide was infused on day 0. Thirty-five of the treated patients were in first remission, 21 were in second or third remission, and six had primary refractory AML and required aggressive salvage regimens to achieve remission. Among patients in first remission, one treatment-related death and five relapses have occurred. With a median follow-up of 25 months, the actuarial relapse rate is 19% +/- 8% and the disease-free survival rate is 79% +/- 8% at 3 years. The 16 patients with favorable FAB subtypes (M3 or M4E0) showed an excellent response to this treatment protocol, with no relapses after median follow-up of 35 months. Among patients in second or third remission, there were five treatment-related deaths and five relapses. With a median follow-up of 41 months, the actuarial relapse rate is 30% +/- 11% and the disease-free survival rate is 52% +/- 11% at 3 years. Four of six primary refractory patients died during treatment and one remains in remission with short follow-up. These preliminary data indicate that aggressive preparative regimens followed by the infusion of purged autologous bone marrow may be a promising approach to improving the clinical outcome of adult patients with AML. PMID- 8342076 TI - Comparison of preparative transplantation regimens using carmustine/etoposide/cisplatin or busulfan/etoposide/cyclophosphamide in lymphoid malignancies. AB - Most bone marrow transplantation preparative regimens use total body irradiation as one component. Recently, however, two non-total body irradiation containing autologous bone marrow transplantation preparative regimens have been evaluated in patients with lymphoid malignancies. The first regimen consisted of carmustine, etoposide, and cisplatin; some patients also received involved-field radiotherapy to sites of prior disease. Of the 79 patients with relapsed or refractory lymphoma who participated in this study, 57 (72%) achieved a complete remission and 40 (51%) remain in complete remission. Treatment-related deaths occurred in five patients (6%). The second preparative regimen evaluated consisted of busulfan, etoposide, and cyclophosphamide and included 21 patients with Hodgkin's lymphoma, non-Hodgkin's lymphoma, or acute lymphocytic leukemia. Sixteen patients (76%) achieved complete remission and 12 (57%) remain disease free. The regimen-related mortality rate in this study was 14%. The three treatment-related deaths were all due to pulmonary toxicity. The results of these clinical trials indicate that both the carmustine/etoposide/cisplatin regimen and the busulfan/etoposide/cyclophosphamide regimen are effective in treating lymphoid malignancies. Treatment-related toxicities and deaths are significant, but not prohibitive. Accordingly, these new preparative regimens deserve further evaluation in the treatment of patients with lymphoma or leukemia. PMID- 8342077 TI - New preparative regimens with diaziquone or cytarabine in combination with busulfan and cyclophosphamide. AB - Preparative regimens used prior to bone marrow transplantation (BMT) in patients with malignancies must mediate engraftment and eradicate malignant cells without producing significant extramedullary toxicities. The first agents to be tested in BMT preparative regimens, total body irradiation (TBI) and cyclophosphamide (Cy), were ineffective as single agents, but resulted in long-term disease-free survival in some leukemic patients when combined. However, Cy/TBI regimens are associated with significant acute and chronic toxicities as well as technical constraints involving the administration of radiation. Accordingly, a nonradiation-based regimen consisting of Cy and busulfan (Bu) was developed. Regimens using either a 4-day course (BuCy4) or a 2-day course (BuCy2) of Cy have been shown to have significant antileukemic effects. In general, however, BuCy regimens do not appear to result in greater antileukemic activity or lower treatment-related toxicity than Cy/TBI regimens. New preparative regimens are currently being developed to lower the incidence of disease recurrence after BMT. One such regimen consists of BuCy plus etoposide. At our institution, we are currently testing the efficacy and toxicity of regimens in which cytarabine or diaziquone are administered in combination with Bu and Cy. It is hoped that these new preparative regimens will enhance the antileukemic effects of BMT without significantly increasing treatment-related toxicity. PMID- 8342078 TI - [Research in health policy]. PMID- 8342079 TI - [The seroepidemiology of rubella in a female population of reproductive age in Leon, Guanajuato]. AB - In order to assess the seroepidemiology of protective antibodies against rubella among women from Leon, Guanajuato, Mexico, a prospective study was done. The sample consisted in 176 serum samples from urban and rural women at reproductive age, drawn from June 1990 to June 1991. Samples were tested by the classic hemagglutination inhibition method, titers of 1:8 or higher were considered as positive. Global positivity was 71 per cent (125 sera). Seropositivity did not increase with women's age; the lowest values were seen at the rural zones (58.9%). This survey showed a lower seropositivity than the previously reported in Mexico, and confirms data from new official studies. With this information authors suggest that the utility and viability of a national vaccination program should be reviewed and propose that it could be risky that individual clinicians to recommend children vaccination because the lack of coordination could increase adult cases of rubella. PMID- 8342080 TI - [Leishmaniasis: a preliminary epidemiological study in a locality of the endemic area in the state of the Tabasco]. AB - The state of Tabasco is localized in the endemic area of cutaneous leishmaniasis where both diffuse cutaneous leishmaniasis and mucocutaneous leishmaniasis have recently been reported. The objective of the present study was to obtain reliable information of the situation of this disease--which has a great relevance as a worldwide public health problem--through determination of the allergic index in a randomized sample from Rancheria Miguel Hidalgo, Comalcalco Municipality, Tabasco, Mexico. We found an allergic index of 56 per cent. Farmers and housewives had the highest positive responses to the Montenegro skin test. We found no statistical differences between males and females. Moreover, 3 patients with active lesions and people with scars suggestive of prior leishmaniasis were detected during the study. This village should be considered a high endemic focus. PMID- 8342081 TI - [Blood transfusion-associated AIDS]. AB - OBJECTIVE: To know the prevalence and epidemiologic characteristics of AIDS related to blood transfusion. DESIGN: This is a retrospective study, conducted from January 1988 to August 1992. PLACE: General Regional Hospital of Mexican Institute for Social Security in Puebla, Mexico. PARTICIPANTS: Inpatients and outpatients attending the hospital and in whom the diagnosis of AIDS stage IV, according to the criteria by the Centers for Disease control, Atlanta, USA, was made. The following criteria were used: age, sex, marital status, date of blood transfusion, amount of blood units transfused, incubation period and course of the disease. STATISTICAL METHODS: The mean, standard deviation, the correlation coefficient and Student t-test were used. RESULTS: Two hundred and forty-seven cases of AIDS were found, 61 of then were related to blood transfusion (24.7%). The mean age was 30 years (SD +/- 9). Thirty-nine out of 61 cases were females (63.9%). The incubation period was 48 months (SD +/- 16) and was shorter in those subjects who received more units of blood, however, this was not statistically significant (P > 0.20). Transmission of the infection to the sexual partner was observed in 6 cases, and perinatal transmission in 2 cases. CONCLUSION: AIDS transmitted by blood transfusion is important; it is more common in females and it is related to the high incidence of HIV infection among commercial donors. Nowadays this mode of transmission is considered virtually absent and a great decrease in transfusion-related AIDS cases is expected in the future. PMID- 8342082 TI - [The prevalence of caries in marginal rural and peripheral urban areas]. AB - A descriptive study of caries prevalence in peripheral urban and rural underprivileged groups was undertaken in self-selected populations demanding basic dental therapy in seven states of Mexico. Dental therapy services were delivered as part of a mobile oral health care program in the Mexican countryside implemented by the Dental School of Universidad Nacional Autonoma de Mexico, during 1990 and 1991. Partial examination of clinical histories of 2,596 patients (mean age 21.8 years) revealed a mean DMFT (the sum of decayed, missing and filled teeth) of 9.21. Only 6.3 per cent of patients had DMFT = 0 and 10.7 per cent were caries-free. The largest component of DMFT were decayed teeth and the smallest one filled teeth. In general, results suggested that caries prevalence was high within the study populations, highlighting the little restorative treatment previously undertaken. The convenience of implementing oral health care schemes to deal with caries morbidity is discussed from the perspective of both the traditional dental treatment approach and preventive public health policies, taking into account the background of complex treatment needs present in these population groups. PMID- 8342083 TI - [Mortality in geriatric patients in the Hospital General of Mexico]. AB - In order to define the main diseases of the elderly and a possible changes of mortality causes at Hospital General of Mexico, SSA, the authors studied 586 autopsy reports of individuals over sixty years old, deceased between 1960 and 1965 and of 625 individuals of similar characteristics deceased between 1981 and 1985. The analysis of diseases showed qualitative and quantitative changes in the ten principal causes of death at each period: some of the most frequent diseases in the 60's, for instance, amebiasis, were not included among the then principal causes of death in the 80's. On the other hand, malignant neoplasms persisted as one of the principal death causes in both periods, but the most frequent carcinoma in the 60's, gastric carcinoma, was substituted in the 80's by bronchogenic carcinoma. This study suggests that great technical and sanitary interventions are necessary to promote health of third age persons, an increasing but poorly protected population in our country. PMID- 8342084 TI - [The opinions of the different participants on community participation in family health and planning]. AB - Community participation constitutes a central strategy in the provision of health services, particularly in poor communities in this country. Little is known, however, about the different actors's point of view regarding this strategy. This is true particularly for female community members and community workers. In this paper, historical antecedents of community participation are discussed and some results of a research work are presented, which explored attitudes and opinions of different groups of interviewees, regarding the idea of community participation in health and family planning. The involved groups are: female community members, community workers, community leaders, medical supervisors which control community workers, and medical executives which control those supervisors. It is emphasized that medical executives are the strongest supporters of community participation, while community members are the weakest. The importance of taking into account the community members' position on matters such as community participation in family planning is stressed. PMID- 8342085 TI - [The construction of a sociocultural epidemiological profile of a rural community]. AB - This study combines two methodological approaches in order to assess morbidity just as it is conceived by the population: the first approach--an anthropological perspective--is a qualitative study of focal groups; the second approach is a sociological study that draws upon participatory research proposals, and intends to related academic interest with the concerns that arise in the population. This research work was conducted with the Health Commission of the main peasant organization in the zone, as part of a health education program working with female peasants who also participated in an ethnobotanical participatory study and in health workshops. The information produced by these women in the two analytical space aforementioned, allowed the indirect conformation of a sociocultural morbidity profile for the zone. Participatory research, focal groups and ethnobotanical studies are useful in the characterization of an epidemiological profile of the sociocultural nature of diseases. In order to conform a synthetic epidemiology, it is necessary to take into account these diseases as health problems that generate poor performance at work, suffering and that deserve to be considered in local health systems (SILOS). PMID- 8342086 TI - [Education by correspondence: a strategy for training and instruction in health services administration]. AB - The training of health services administration professionals in Mexico has faced two main challenges. One the one hand, the need to have recognition as professionals, and on the other hand the difficulty to train individuals that are currently working as health care administrators. This article emphasizes a distance education strategy as an alternative to provide training to these type of personnel. A proposal developed as the second phase of the Advance Education Program on Health Administration (PROASA-II) is presented. It has the objective to strengthen local institutions to take responsibility for the future training of their professional administration staff. Once that this is started, we can begin to talk about the creation of a national system of manpower training in health administration and public health, that will support the decentralization and the appropriate training of the different levels of health administration in the country. PMID- 8342087 TI - [Razon de posibilidades: a proposed translation of the term odds ratio]. AB - In English, odds ratio is a basic epidemiological measure approximating the relative risk. Odds ratio has been translated into Spanish in several ways, which has produced great terminological confusion. On the other hand, the English word odds is often used in epidemiology or statistics English textbooks, alone or as part of other expressions, but always keeping a definite mathematical meaning, which calls for a similarly definite term in Spanish. We discuss several translations of odds ratio found in the literature and propose the Spanish word "posibilidades" as a translation of odds and "razon de posibilidades" as a translation of odds ratio. PMID- 8342088 TI - [Rice and beriberi. A preliminary report on an experiment performed in the Asylum for the Insane of Kuala Lumpur. 1907]. PMID- 8342089 TI - Bone marrow toxicity by silver sulfadiazine. AB - The effect of silver sulfadiazine (SSD) on the production of granulocytes and macrophages was studied in a murine model of cutaneous injury. Application of SSD daily to mice receiving a 10 percent full-thickness total body surface area burn injury failed to demonstrate consistent suppression of the bone marrow at one, four or seven days postinjury. Mice undergoing a 10 percent full-thickness skin excision (SE) and daily SSD application (SE plus SSD) had a near 50 percent reduction in total peripheral blood leukocyte counts in comparison with a control group and untreated mice that were skin-excised (SE-U) (p < 0.03) to 0.002) on day one postinjury and maintained this reduction compared with SE-U at days four and seven postinjury. The absolute number of granulocytes in SE plus SSD was only 10 percent of control or SE-U (p < 0.04 to 0.002) at day one postinjury and remained less than SE-U at four and seven days postinjury. Femoral bone marrow assay of granulocyte-macrophage progenitor cells (GM-CFC) revealed a marked reduction in nucleated bone marrow cells for SE plus SSD compared with respect to control at days one and seven and SE-U at days four and seven (p < 0.02 to 0.001). GM-CFC were significantly depressed in SE plus SSD on day one compared with C and SE-U and day four compared with SE-U (p < 0.01 to 0.001), but returned to control values by day seven. When SSD (0.5 to 500.0 micrograms per milliliter) was added to culture plates containing maximally stimulated normal murine or human bone marrow cells, the colony count was depressed in a dose-dependent manner. In vitro SSD is directly cytotoxic to myelopoietic tissue, and in vivo, alters the myeloid cell compartment. These observations in combination may explain the transient leukopenia frequently observed in patients receiving topical chemoprophylaxis with SSD. PMID- 8342090 TI - Surgical bleeding in microgravity. AB - A surgical procedure performed during space flight would occur in a unique microgravity environment. Several experiments performed during weightlessness in parabolic flight were reviewed to ascertain the behavior of surgical bleeding in microgravity. Simulations of bleeding using dyed fluid and citrated bovine blood, as well as actual arterial and venous bleeding in rabbits, were examined. The high surface tension property of blood promotes the formation of large fluid domes, which have a tendency to adhere to the wound. The use of sponges and suction will be adequate to prevent cabin atmosphere contamination with all bleeding, with the exception of temporary arterial droplet streams. The control of the bleeding with standard surgical techniques should not be difficult. PMID- 8342091 TI - Mediastinal drainage prevents fatal pyothorax from anastomotic leakage after intrathoracic anastomosis in reconstruction for carcinoma of the esophagus. AB - In our experience, anastomotic leakage occurred in five of 69 patients with intrathoracic anastomosis after resection of carcinoma of the esophagus. In the early period, only an ordinary right thoracic drain was put in place, and when leakage occurred, two patients died because of pyothorax, while one patient was saved by surgical drainage. However, in the recent period, in addition to the ordinary right thoracic drain, another drain has also been placed just distal to the anastomosis through the esophageal hiatus through the abdominal cavity, exiting the abdominal wall. After such procedure, drainage has been adequate without any occurrence of pyothorax, even when anastomotic leakage occurred, as in the two most recent instances. Therefore, unless drainage is inadequate and surgical drainage is indicated, as in instances of necrosis of substitutes, mediastinoabdominal drainage seems to be effective in the treatment of intrathoracic anastomotic leakage. PMID- 8342092 TI - Microsurgery alone or with INTERCEED Absorbable Adhesion Barrier for pelvic sidewall adhesion re-formation. The INTERCEED (TC7) Adhesion Barrier Study Group II. AB - Adhesion re-formation after a reproductive operation, particularly involving the pelvic sidewall, is a prominent cause of failure in the surgical treatment of infertility. This study was done to evaluate the impact of standard microsurgery through laparotomy and the additional benefit of an oxidized regenerated cellulose adhesion barrier (INTERCEED [TC7] Absorbable Adhesion Barrier [Ethicon Inc.]), in reducing pelvic sidewall adhesion re-formation. One hundred and thirty four patients with bilateral pelvic sidewall adhesions undergoing adhesiolysis by standard microsurgical techniques through laparotomy were treated during a prospective randomized trial involving 13 centers. After adhesiolysis, the deperitonealized surface of one pelvic sidewall was randomly assigned to be covered with INTERCEED Barrier, the contralateral sidewall serving as control. A second-look laparoscopy was performed ten days to 14 weeks postoperatively. Microsurgical adhesiolysis alone resulted in 24 percent of the sidewalls becoming free of adhesions and a 55.6 percent reduction in the area of adherent peritoneum. With microsurgery alone, 60 and 39 percent of adhesions initially characterized as filmy or severe, respectively, were not seen at second-look laparoscopy. The use of INTERCEED Barrier increased the incidence of adhesion free sidewalls twofold. The treatment was also associated with a statistically significant reduction in the area of peritoneum affected by adhesion re formation, compared with the control wall. Of the adhesions originally graded as severe, 61 percent of those treated with INTERCEED Barrier did not re-form at all. When evaluated on filmy adhesions, the use of the barrier was associated with a 72 percent reduction in adhesion re-formation. A measurable reduction in adhesion re-formation was found, depending on the initial adhesion type, with microsurgery alone. The addition of INTERCEED Barrier further reduced the incidence, extent and severity of postoperative adhesion re-formation. In this study, 90 percent of the patients benefited from the use of INTERCEED Barrier. PMID- 8342093 TI - Helium insufflation for laparoscopic operation. AB - Laparoscopic surgical procedures are becoming simultaneously more commonplace and complex. However, carbon dioxide (CO2) pneumoperitoneum required for these procedures causes a respiratory acidosis. We undertook this study to determine if an alternate insufflating gas, such as helium, prevents this sequelae. Twenty patients undergoing elective laparoscopic cholecystectomy were randomized to receive either CO2 or helium insufflation. Intraoperative parameters, including arterial CO2 (PaCO2), end-tidal CO2, pH, bicarbonate (HCO3-), cardiac output and blood pressure were obtained before, during and at the conclusion of pneumoperitoneum. Effects of the two gases on these variables were compared. The average CO2 rose significantly from 35.7 +/- 1.0 to 50.4 +/- 3.2 (p < 0.0001), while pH decreased from 7.434 +/- 0.014 to 7.286 +/- 0.018 (p < 0.0001) in those who received CO2. No change in PaCO2 was observed in those who received He, although a small decrease in pH from 7.428 +/- 0.011 to 7.392 +/- 0.012 (p < 0.05) was observed. HCO3- decreased slightly in both groups. Increases in blood pressure and pulse rate were independent of the gas received. The cardiac output did not change. Helium insufflation for laparoscopic cholecystectomy does not produce the respiratory acidosis caused by CO2 and, therefore, merits further investigation for use, particularly in patients with underlying respiratory disease. PMID- 8342094 TI - Intraoperative fine needle aspiration of pancreatic and extrahepatic biliary masses. AB - Intraoperative fine needle aspiration (IFNA) of masses of the pancreas and extrahepatic biliary system provides a method of rapid tissue diagnosis with a much lower complication rate than either wedge or large bore needle biopsies. Few series include IFNA of extrahepatic biliary system masses in their analyses. We retrospectively evaluated all IFNA of pancreatic, extrahepatic biliary and ampullary masses at the University of Virginia from March 1981 to December 1991 to assess the diagnostic accuracy of this procedure. Ninety-nine IFNA were performed--75 of the pancreas, 17 of the extrahepatic biliary system and seven of the ampulla. All aspirations were performed with direct visualization or palpation of the tumor, or both, using several passes with a 22 gauge needle. A diagnostic "positive" or "negative" reading was rendered in 90 of 99 IFNA. Carcinoma was confirmed by positive tissue diagnosis or clinical course consistent with cancer. Benign disease was confirmed by negative pathologic factors from a resected specimen or confirmatory clinical course of at least 18 months. Diagnosis was confirmed by these criteria in 82 patients. Thirty-four of 43 patients with confirmed carcinoma of the pancreas had positive cytologic factors by IFNA. Three pancreas IFNA were deemed as "suspicious" and six as "unsatisfactory." Two patients with "suspicious" findings had pathologically confirmed well-differentiated carcinoma. Carcinoma of the ampulla and extrahepatic biliary tract was detected by IFNA in 17 of 18 confirmed patients. The overall sensitivity of positive or negative IFNA in this series in 90 percent, with 100 percent specificity and 92 percent accuracy. IFNA has a positive predictive value of 100 percent and negative predictive value of 74 percent. We conclude that IFNA is a highly accurate diagnostic procedure and represents the preferred technique of obtaining an intraoperative tissue diagnosis in masses of the pancreas, extrahepatic biliary tract and ampulla. Positive IFNA may definitively guide surgical decision-making; however, we caution that negative IFNA cannot be relied on definitively to exclude the diagnosis of carcinoma. PMID- 8342095 TI - Outcome of surgical treatment for extrapancreatic gastrinomas. AB - Since the availability of the H2-receptor antagonists (1978), seven patients admitted to the Department of Emergency Surgery, University of Pisa, with Zollinger-Ellison syndrome (ZES) sustained by extrapancreatic gastrinomas underwent elective surgical treatment. There were four women and three men, with a mean age of 37.3 years (16 to 67 years of age). Preoperative localization studies included endoscopy of the upper part of the gastrointestinal tract, computed axial tomography, ultrasound, selective angiography and transhepatic portal vein sampling for gastrin and were effective in four patients. In the other three patients, the localization of the gastrinoma was made at laparotomy. Four patients had gastrinomas of the duodenal and jejunal wall. Three underwent excisional operations, whereas the remnant was treated with pancreatoduodenectomy. In three of the patients, the location of the gastrinoma was extrapancreatic and extraintestinal, and surgical treatment consisted of nodal excision (two patients) and hepatectomy. None of the patients had undergone a gastric operation in addition to tumorectomy procedures. Soon after excisional operation, ZES recurred in one patient and a second laparotomy with nodal excision resulted in a cure. On long term follow-up evaluation, ranging from 15 to 136 months (mean of 85.1 divided by 37.3 months), no patients showed a recurrence of ZES. The possibility of extrapancreatic gastrinoma should be suspected in patients with sporadic ZES. The need for emergency surgical treatment in these patients is minimized by the medical control of the gastric secretion that consents diagnostic studies for the preoperative localization of the gastrinoma. Even if only suspected, the site of the extrapancreatic gastrinoma has an increased chance to be identified at operation. This consents to remove gastrinomas mostly by a minimal excisional procedure resulting in the normalization of gastric secretion and the prevention of malignant evolution of these tumors. PMID- 8342096 TI - Surgical treatment for congenital absence of the vagina using tissue expansion. AB - A modification of the Abbe-McIndoe technique for the treatment of congenital absence of the vagina, using a cylindrical tissue expander wrapped in a mesh split-thickness skin graft, instead of a rigid silicone mold, is presented. The expander was kept in place for a period of two to six months and the functional result was 100 percent in all the six patients treated. Our experience led us to change the design of the expander (cylindrical, without ring, 10X4 centimeters) and to place the valve in the inner thigh as the best site for the valve. The age range of the patients was 18 to 27 years, and the final result was good or very good in five of the six women. Only one patient has occasional dyspareunia, which does not prevent sexual intercourse. PMID- 8342097 TI - The analysis of benefit and risk of combined pancreatic and renal transplantation versus renal transplantation alone. AB - Currently, diabetes mellitus is the most common cause of renal failure in adults. However, combined pancreatic and renal transplantation (PRT) remains controversial when compared with renal transplantation alone (RTA) in diabetic recipients. We analyzed the results and morbidity in four age-matched groups--31 patients with Type I diabetes undergoing PRT before dialysis, 30 patients with diabetes who are dependent of dialysis undergoing PRT, 31 concurrent and historic patients with Type I diabetes undergoing RTA and 31 concurrent patients without diabetes undergoing RTA. All patients received cadaver donor organs and were managed with cyclosporine and prednisone immunosuppression with selective OKT3 induction. The four groups were comparable with respect to age, weight, gender, duration and severity of diabetes, dialysis type, number of retransplants, degree of sensitization, preservation time and matching. The groups differed with regard to duration of dialysis and period of follow-up evaluation, pretransplant blood transfusions, racial distribution and OKT3 induction therapy. PRT was associated with a greater morbidity rate as evidenced by a slightly higher incidence of rejection, infections and reoperations. The number of readmissions and hospitalization period during the first 12 months was also greater after PRT versus RTA. However, none of these differences were significant. No detrimental effect was noted on renal allograft function at one year; patient and graft survival was actually higher in the PRT groups. Quality of life was improved in nearly 90 percent of PRT recipients. Although the improved results after PRT may be attributed to selection bias, only lesser differences were noted among the four study groups. The aforementioned data suggest that appropriate patient selection can overcome the morbidity associated with PRT, resulting in excellent patient and graft survival with the potential for complete rehabilitation. PMID- 8342098 TI - Patient-controlled analgesia and postoperative urinary retention after open appendectomy. AB - We retrospectively studied 279 patients who had undergone uncomplicated open appendectomy for acute appendicitis to determine risk factors for postoperative urinary retention. The gender of the patients, the operating time and the amount of fluid given perioperatively had no influence on the occurrence of retention. The amount of analgesic agent administered postoperatively and the age of the patient were significantly associated with urinary retention (p = 0.01 and p < 0.0001, respectively, after adjustment for potential confounding factors). The use of meperidine hydrochloride as compared with morphine and of patient controlled analgesia as compared with intramuscular delivery were initially found to be significantly related to retention (p = 0.014 and p < 0.0001, respectively). After the effects of the age of the patient, the drug type and the amount of fluid and analgesic agent administered were controlled for, patient controlled analgesia remained significantly associated with retention (p < 0.0001), whereas the type of drug given was no longer significant after controlling for potential confounding factors. Because we found that urinary retention was 13 times more likely to occur in the patients who had patient controlled analgesia, we recommend that the use of this form of analgesia delivery be avoided after open appendectomy. PMID- 8342099 TI - An inexpensive and versatile intraluminal shunt for vascular operations. AB - An inexpensive and versatile intraluminal shunt for vascular operation is presented. The shunt is created using two urinary catheters and a three-way stopcock. This shunt can be used for perfusion in patients with trauma and prolonged revascularization in the lower part of the limb. Various procedures are easy to perform using this shunt without any manipulation of the vessel or shunt. Furthermore, and more importantly, this shunt can be created and used in any hospital. PMID- 8342100 TI - Cystopancreaticostomy and longitudinal pancreaticojejunostomy as a simpler technique of combined drainage operation for chronic pancreatitis with pancreatitis with pancreatic pseudocyst causing persistent cholestasis. AB - A simpler combined drainage operation for a patient with chronic pancreatitis and chronic pseudocyst is described in the following conditions: the pancreatic duct was markedly dilated, the cyst was located directly behind the main pancreatic duct in the head of the pancreas and separate from the duodenum and the cyst caused persistent CBD stricture and cholestasis mainly by its compressive effect. The pancreatic duct was opened anteriorly throughout its length. A second incision was made in the posterior wall of the main pancreatic duct into the cyst and the edge of the opening was sutured for hemostasis. The opened pancreas was anastomosed to a Roux-en-Y jejunal limb according to the ordinary method of longitudinal pancreaticojejunostomy. This technique, cystopancreaticostomy and pancreaticojejunostomy, may provide a simpler and effective operative strategy for patients with chronic pancreatitis and pseudocyst in similar conditions. PMID- 8342101 TI - Internal marsupialization after laparoscopy for lymphoceles after renal transplantation. PMID- 8342102 TI - Gastrojejunal disconnection in the presence of purulent peritonitis as an alternative approach in gastroduodenal operations. AB - A two stage operation is presented, for example, a life-saving procedure that halts further leakage and drainage of abscess by a modification of the gastrojejunal disconnection and reconstruction. It may be considered as an alternative approach in gastroduodenal operations in the presence of purulent peritonitis, especially in delayed surgical treatment. PMID- 8342103 TI - A technique for securing transperitoneal tubes. AB - A simple technique for securing transperitoneal tubes is described. We believe this technique results in a tube fixation that is less traumatic to the surrounding skin, is difficult to remove accidentally and is easier to replace. PMID- 8342104 TI - The life of Joseph Colt Bloodgood, M.D., public surgeon. PMID- 8342105 TI - The surgical management of obstruction and perforation of the left colon. AB - Patients requiring emergency surgical treatment of the left side of the colon have a poor prognosis. Age, advanced malignant disease and systemic sepsis are contributory factors to the high morbidity and mortality rates, but making surgical decisions is also important. Any surgeon is likely to encounter only a few such patients per year and this adds to the uncertainty regarding management. Although the traditional three-staged approach was based on safety, it has been demonstrated that immediate resection is feasible and beneficial in most patients. This should be accompanied by primary anastomosis in all instances except in the presence of generalized peritonitis or a large abscess cavity causing severe systemic sepsis. When such circumstances occur, resection with terminal colostomy is the safest policy. We conclude that multicenter randomized prospective clinical trials should be initiated to establish the optimum and most economic method of resection and primary anastomosis for emergency operation of the left side of the colon. PMID- 8342106 TI - Prostate surgery expenses, 1991. AB - During 1991, average total charges for a radical prostatectomy among MetLife group health policy holders and dependents averaged $18,140; comparable charges for a transurethral resection of the prostate (TURP) were $7,970. The Pacific area reported the highest average total charges for both procedures--charges 25 percent above the U.S. average for both surgeries. Among the 14 states with 10 or more radical prostatectomies reported to MetLife, California led with total charges of $24,850 (37 percent above the U.S. average) and Minnesota reported the lowest average total charges ($12,480, 31 percent lower than the norm). In the 32 states with 10 or more TURPs during 1991, the charges ranged from the highest in Massachusetts ($11,250, 41 percent above average) to the lowest in Washington ($5,170,35 percent below the United States). Just over two-thirds of the total charges for each surgical procedure was due to the hospital portion of the bill. Physician charges were more than twice as high for a radical prostatectomy than for a TURP, e.g., $5,730 versus $2,630. Hospital stays averaged 7.5 days for a radical prostatectomy and 4.3 days for a TURP. The stays were longest in New Jersey for both procedures. PMID- 8342107 TI - The evolving American family. AB - The American family is undergoing profound changes. In the past few decades the traditional two-parent family has dramatically decreased while the one-parent family has become more prevalent. Currently, just seven out of 10 children under 18 years of age live with both mother and father; in 1960 the ratio was nearly nine out of 10. During this interval, premarital childbearing, separation and divorce increased rapidly, with the result that the percentage of children residing with just one parent virtually tripled--from 9 percent to 26 percent. Parental characteristics of single- and two-parent families with children under 18 showed significant differences among racial groups. PMID- 8342108 TI - Trends in urinary tract cancer deaths. AB - Death from cancer of the urinary tract (bladder, kidney and renal pelvis) continues to be the fourth leading cause of cancer mortality among U.S. men. In 1988-89, 21,834 deaths from urinary tract cancer occurred among men aged 45-84 years, resulting in an age-adjusted mortality rate of 25.9 per 100,000. This rate was 7.2 lower than that reported for 1979-81 and all but 16 states had lower rates in 1988-89 than in 1979-81. The rates decreased or remained the same in all but the West South Central area of the country where there was a 2.5 percent increase in 1988-89. In states with 200 or more deaths from urinary tract cancer, the largest decrease in the age-adjusted mortality rate for men 45-84 was evident in New York and Virginia. The 16 rate increases ranged from 24 percent in Wyoming with 44 cases to 0.4 percent in Minnesota with 393 cases and 0.3 percent in Indian with 529 cases. PMID- 8342109 TI - International death rates compared. AB - Since 1950 substantial progress has been made in reducing mortality in the United States. The decline in age-adjusted death rates was especially notable among women and among nonwhite persons. In particular, women of all other races recorded a precipitous reduction in death rates. Notwithstanding, age-adjusted death rates in the United States are still higher than those in other countries with traditionally low mortality. Moreover, very little progress has been achieved in the past decade in narrowing the international mortality gap. Currently, the United States ranks eleventh out of 15 countries under review. Men and women in Japan have the best mortality record. PMID- 8342110 TI - [Radiosynoviorthesis]. AB - Intraarticular therapy using radionuclides seems to be the best conservative local treatment of chronic synovitis as a generally accepted alternative to surgical synovectomy. If the indication is carefully considered and the technique properly applied, the success rate of treatment is as high as it is with surgery, whereas the risk involved is comparatively low. PMID- 8342111 TI - [The primary radiotherapy of inoperable or recurrent pancreatic carcinoma- Heidelberg patients from 1982 to 1992]. AB - Between 1982 and 1992, 34 patients with locally advanced or relapsed adenocarcinoma of the pancreas were treated at the Department of Radiotherapy in Heidelberg. 14 patients were treated with a combined radiochemotherapy with 5-FU, the other patients were irradiated alone. In all cases irradiation was done with high energy photons. 15 patients received an irradiation with doses between 30 and 44 Gy, and twelve patients between 45 and 66 Gy (median 50 Gy). Seven patients were treated intraoperatively during an exploration laparotomy with fast electrons (10 to 18 MeV, 15 to 20 Gy) and postoperatively with additional 30 to 41 Gy. The median survival of the patients treated with the higher doses or in combination with the IORT showed a significant advantage of nine vs. 2.9 months. There was no benefit in median survival for the patients treated with radiochemotherapy. In retrospective analysis of the percutaneous treated patient collective a pain relief was observed in nine patients. In the prospective treatment protocol of the IORT in 4/4 patients a pain relief was rapidly reached. PMID- 8342112 TI - The RBE of negative pions in the treatment of tumors with different volumes. AB - For negative pions, large differences exist between experimental RBE values obtained by in vivo investigations with animals and corresponding data being used in clinical tumor therapy. Therefore, the influence of the treatment volume on the radiation quality and respectively on the RBE is examined. The RBE for euoxic mammalian cells is measured with high precision in different volumes irradiated in the spot-scan mode with the PIOTRON at the Paul Scherrer Institute. It is shown experimentally that the RBE is reduced if the radius of the irradiation volume is increased. Using a simple mathematical approximation for the spot-scan technique this relation can be understood quantitatively. The same approximation is also used to calculate dose mean values for the lineal energy yD present in different irradiated volumes. The good agreement with existing experimental data for yD indicates that the approximation used is adequate and the main physical parameters have been taken into consideration. The above mentioned differences between animal experiments and treatment of patients can be explained by changes in the effective radiation quality due to the scanning procedure used in the clinical treatments. PMID- 8342113 TI - Tumor response to ionizing radiation and combined 2-deoxy-D-glucose application in EATC tumor bearing mice: monitoring of tumor size and microscopic observations. AB - The present study deals with the changes induced by two fractionation schedules (5 x 9 Gy and 10 x 4.5 Gy; 30 MeV-electrons) of ionizing radiations and 2-deoxy-D glucose (2-DG) application on EATC tumor bearing swiss albino mice. The monitoring of tumor response was carried out by means of caliper measurement on the macroscopic level and by histopathological examination of tumor preparations stained with hematoxiline and eosine on the microscopic level. The tumor material was assessed at suitable intervals after treatment by killing the animals. The tumor response was analysed in the histological preparations and the thickness of the tumor band was determined quantitatively by an ocular micrometric technique. Tumor damage was most extensive in the combined treated animals (5 x 9 Gy + 2 DG). Only in this group local tumor control was achievable. The histological analysis of tumor preparations revealed additional data about treatment-induced changes in the tumor compared to the measurement of the tumor volume with mechanical calipers. We also found that the treatment outcome could be predicted from the histopathological analysis. It is concluded that studies involving histopathological examinations may give some insight into the way cancer is controlled by radiotherapy and may be of value in prognosis and selection of treatment in patients. PMID- 8342114 TI - [The relative biological effectiveness (RBE) of fast neutrons on the Dunning rat prostate carcinoma R3327-HI]. AB - Human prostate tumors are known to be good candidates for neutron therapy. The Dunning rat prostate tumor system R3327 was found in many studies to be an excellent model for human prostate tumors. There is still a paucity of studies on the response of the Dunning tumors to fast neutrons. Tumors of the R3327-HI subline are moderately well differentiated and mucin producing. They show one euploid cell population, a bromodeoxyuridine labelling index of 5%, a potential doubling time of 8.9 days, a volume doubling time of about ten days and a cell loss rate of 10%. Tumors were transplanted s.c. in the distal thigh of Copenhagen rats and treated with 60Co-photons (10, 20, 30, 40 Gy, 45 cGy/min) and 14-MeV neutrons (8, 10, 12 Gy, 7 to 11 cGy/min). Tumor volumes were measured twice weekly. Growth delay was defined as time in days until the tumors reached twice their treatment volume. Linear regressions on the median growth delays of the different treatment groups were calculated. The ratio of the neutron- and photon slopes yielded an RBE of 3.1 +/- 0.3. Additionally isoeffect-RBE values between 2.3 and 2.6 were graphically estimated. PMID- 8342115 TI - Effect of whole-body irradiation on phagocytic cells in mouse blood measured by chemiluminescence. AB - In investigations with mice the influence of an X-irradiation on the chemiluminescence yield of granulocytes from the peripheral blood was measured. The measurements were carried out with diluted freshly drawn blood by adding luminol as chemiluminogenic substance. The granulocytes were stimulated by zymosan. The following dependencies were investigated: dose from 1 to 8 Gy and time twelve hours to 32 days after a whole-body irradiation. In general the chemiluminescence yields from blood of irradiated animals are reduced in dependence of dose compared with the findings in controls. In unirradiated animals (controls) there exists a good correlation between the numbers of granulocytes and the chemiluminescence. This correlation is diminished after an irradiation. For the fourth day after a whole-body irradiation the chemiluminescence shows an exponential dose dependence. If chemiluminescence counts are related to the number of granulocytes (relative chemiluminescence) an increased chemiluminescence per single granulocyte is recorded up to the eighth day after an irradiation with 1 Gy. It may be assumed that subpopulations of granulocytes with enhanced ability to form oxidative metabolic products are responsible for this effect. PMID- 8342116 TI - Linear quadratic model--estimation of alpha/beta ratio for mucosal reaction. AB - In radiotherapy to ensure that appropriate tumor lethal dose is delivered without exceeding normal tissue tolerance, concepts like NSD and its derivatives were used in the past. Due to their short coming these concepts are now replaced by a linear quadratic model. As this model is based on the recent radiobiological data, it is claimed to be able to predict the biological responses of tumors as well as normal tissues more accurately. However, the accuracy of prediction depends on the precise values of various parameters such as alpha/beta, repair constant mu and repopulation factor that are involved in the linear quadratic model. For most of the tumors and normal tissues, values of the parameters are not yet accurately known. We have estimated alpha/beta value for mucosal reactions, i.e. normal tissue early reactions in head neck cases treated with twice daily fractionation schedules and observed it to be 7.90 Gy for slight mucositis whereas it is 7.68 and 8.11 Gy for patchy and confluent mucositis, respectively. PMID- 8342117 TI - Systemic radiotherapy with monoclonal antibodies. An experimental study with human neuroblastoma xenografts in nude mice. AB - In this experimental study, feasibility and efficiency of systemic radiotherapy with the I-131 labelled monoclonal antibody BW575/9 (radioimmunotherapy) are investigated using human SK-N-SH neuroblastoma transplanted into nude mice. Series of six nude mice were treated with intravenous application of 400 microCi (group 1), 700 microCi (group 2) of the I-131 labelled and of the unlabelled MAb (group 3). An untreated group (group 4) served as control. Tumors of group (3) and (4) showed an identical growth. In group (1), tumor growth was arrested for seven days. In group (2), the tumor showed complete regression after eight days which lasted for 55 days. Thereafter, the tumor started to regrow. This growth characteristics are correlated with the doses achieved in the tumor using a medical internal radiation dose (MIRD) formulation. The biodistribution data necessary for MIRD calculation were obtained by previously performed experiments with the I-125 labelled MAb. The doses assessed in the tumor turned out to be five to ten times greater than those in normal tissues (liver, bone, etc.) These results confirm feasibility, selectivity and efficiency of radioimmunotherapy in the above described model. Moreover, this in vivo model seems suitable for further investigations concerning fundamental issues of radioimmunotherapy. PMID- 8342119 TI - Zen and the art of surgery. PMID- 8342118 TI - Measurement of the proliferative activity of three different sublines of the Dunning rat prostate tumor R3327. AB - The development of the BrdUrd assay has greatly facilitated the measurement of proliferation in both human and experimental tumors. The potential doubling time (Tpot) was reported to be the most promising parameter to serve as a predictive assay to select patients for new treatment modalities such as accelerated fractionation and fast neutrons. We compared flow cytometry and immunochemistry applied to three sublines of the Dunning rat prostate tumor with differing differentiation. The anaplastic R3327-AT subline has a labeling index (LI) of 7 +/- 0.5% and 8.8 +/- 3.7 measured with flow cytometry and histology respectively, S-phase duration (Ts) of 8 h, a Tpot of 4.7 days and a cell loss factors (phi) of 15%. Proliferating cells are homogeneously distributed. The moderately well differentiated R3327-HI subline shows a LI of 5% (flow cytometry 5 +/- 0.5%, immunohistochemistry 5 +/- 2%), Ts of 10.7 h, Tpot of 8.9 days and phi of 10%. The well differentiated subline R3327-H has two cell populations (DNA-index 1.6) and a labeling index of 3.7 +/- 0.5% measured with flow cytometry and 2.2 +/- 0.4% with immunochemistry. PMID- 8342121 TI - Arginine stimulates wound healing and immune function in elderly human beings. AB - BACKGROUND: Experimentally, arginine enhances immune function and promotes wound healing. In this randomized double-blind study we investigated the effect of oral arginine supplementation on wound healing and T-cell function in elderly human beings (more than 65 years of age). METHODS: Thirty elderly, healthy, human volunteers (15 men and 15 women) received daily supplements of 30 gm arginine aspartate (17 gm free arginine). Fifteen volunteers (nine men and six women) received a placebo syrup. Fibroplastic wound responses were assessed by inserting a polytetrafluoroethylene catheter subcutaneously into the right deltoid region. Epithelialization was examined by creating a 2 x 2 cm split thickness wound on the lateral aspect of the upper thigh. Mitogenic response of peripheral blood lymphocytes to concanavalin A, phytohemagglutinin, pokeweed mitogen, and allogeneic stimuli was assayed at the beginning and end of supplementation. Polytetrafluoroethylene catheters were analyzed for alpha-amino nitrogen (assessment of total protein accumulation), hydroxyproline (index of reparative collagen synthesis), and DNA accumulation (index of cellular infiltration). RESULTS: Arginine supplementation for 2 weeks significantly enhanced wound catheter hydroxyproline accumulation (26.49 +/- 2.39 nmol/cm vs 17.41 +/- 2.04 nmol/cm) and total protein content (43.47 +/- 3.85 micrograms/cm vs 21.95 +/- 2.5 micrograms/cm). Arginine did not influence the DNA content of the catheters or the rate of epithelialization of the skin defect. Peripheral blood lymphocyte responses to mitogenic and allogenic stimulation were greater in the arginine supplemented group. Serum insulin-like growth factor-1 levels were significantly elevated in the arginine group. CONCLUSIONS: The data suggest that arginine supplementation may improve wound healing and immune responses in the elderly. PMID- 8342120 TI - Role of bactericidal permeability-increasing protein in the treatment of gram negative pneumonia. AB - BACKGROUND: Gram-negative infections are a major cause of morbidity and death. Bactericidal permeability-increasing protein (BPI) is an endotoxin-neutralizing protein that also exhibits potent bactericidal activity. This study compared the efficacy of a 23 kd recombinant N-terminal fragment of BPI (rBPI23) with that of antiendotoxin antibody E5 in a model of gram-negative sepsis. METHODS: Sixty Swiss-Webster mice (Carworth farm) received an intratracheal inoculation of Escherichia coli (7 x 10(6) colony-forming units) and were randomized to three groups (20 per group). Starting immediately after inoculation, the groups received either rBPI23 (4 mg/kg intravenously every 2 hours for four doses), E5 (11 mg/kg intravenously every 24 hours for two doses), or an isotype control antibody B55 (11 mg/kg intravenously every 24 hours for two doses) and were followed up for survival. In a second survival study, 40 mice received the same intratracheal inoculation of E. coli and were randomized to two groups. Starting 2 hours after inoculation, the groups received either rBPI23 (4 mg/kg intravenously every 2 hours for four doses) or E5 (8 mg/kg intravenously every 12 hours for four doses) and were followed up for survival. In a third study, mice received an intratracheal inoculation of 3 x 10(6) colony-forming units E. coli, a sublethal dose, and were killed to determine pulmonary and blood clearance of bacteria. RESULTS: rBPI23 conferred significantly greater protection from death than either E5 or B55 when started immediately (95% survival vs 20% and 10%, respectively; p < 0.001) or 2 hours after inoculation (65% survival vs 25% for E5; p < 0.05). Both pulmonary and vascular clearance of bacteria was enhanced significantly by treatment with rBPI23. CONCLUSIONS: rBPI23 may be a novel therapeutic agent in the management of gram-negative sepsis. PMID- 8342122 TI - Extracorporeal life support for adult cardiorespiratory failure. AB - BACKGROUND: Extracorporeal membrane oxygenation is routinely used for neonatal respiratory failure but is considered unsuccessful in adults based on old studies and old methods. We conducted a new phase 1 trial of modern extracorporeal life support (ECLS) in moribund adults with cardiorespiratory failure. METHODS: Criteria for initiation of ECLS were 90% mortality risk despite maximal conventional care, good potential for recovery, age < 60 years, and no contraindication to anticoagulation. Vascular access for ECLS was performed by operative or percutaneous cannulation. Continuous systemic heparinization was used, maintaining whole blood activated clotting time between 160 to 180 seconds. Blood components were transfused as necessary. Lung management included low rate and low pressure ventilation with an inspired oxygen fraction 0.5 or less. RESULTS: Forty patients were treated with ECLS, 30 with primary respiratory failure and 10 with primary cardiac failure. Twenty-two patients recovered lung or heart function, and 18 patients survived and were discharged from the hospital (14 with respiratory failure and four with cardiac failure, overall survival 45%). The major complication of ECLS was bleeding. CONCLUSIONS: With modern techniques, ECLS can be lifesaving in adult cardiorespiratory failure when conventional therapy has failed. PMID- 8342123 TI - Use of gene therapy to induce human-mouse xenogeneic chimerism. AB - BACKGROUND: Bone marrow transplantation (BMT) has been used in the laboratory to overcome the immunologic barriers to xenotransplantation and results in chimerism and specific tolerance to donor antigens in lethally irradiated mice. Clinically, BMT carries the considerable risks of graft-versus-host disease and graft failure. Retrovirus-mediated gene transfer could provide a means of introducing foreign major histocompatibility (MHC) genes into host bone marrow cells (BMC) and thus accomplish the immunologic goals of BMT, without the associated risks. METHODS: Using a Moloney virus-based vector, a replication defective retrovirus was constructed that contained a complementary DNA encoding the human MHC antigen HLA-A2. Three million C57BL/6 mouse BMC were cocultured for 48 hours with 1 x 10(6) HLA-A2 virus "producer" cells in the presence of 15% WEHI supernatant (interleukin-3) and 200 units/ml interleukin-6. Putatively infected BMC were then used at 2 to 3 x 10(6) BMC/animal to reconstitute lethally irradiated syngeneic mice. RESULTS: Twelve days after reconstitution, spleen colonies were found to have integrated the full-length retroviral sequences. Thirty days after BMT, the introduced DNA could be found in the bone marrow, thymus, and spleen, and approximately 5% of T cells in the spleen expressed the HLA-A2 surface antigen. CONCLUSIONS: These data show that xenogeneic MHC genes can be introduced and expressed in mouse hematopoietic cells in vivo and indicate that gene therapy potentially may be used in the future to manipulate the immune system to induce transplantation tolerance. PMID- 8342124 TI - Prevention by thymectomy of tolerance induced by intrathymic injection of donor splenocytes. AB - BACKGROUND: We have recently demonstrated indefinite donor-specific cardiac allograft survival after the intrathymic injection of donor splenocytes and simultaneous injection of antilymphocyte serum (ALS) in a fully major histocompatibility complex-mismatched rat combination. In this study we performed thymectomy to determine the length of time required for donor alloantigen to be present in the recipient thymus to induce tolerance. METHODS: Male Buffalo (BUF; RT1b) rats at 4 to 8 weeks of age underwent intrathymic injection of 25 x 10(6) Lewis (LEW; RT1(1)) splenocytes and simultaneously received an intraperitoneal injection of 1 ml ALS. To determine the kinetics of tolerance induction, the BUF recipients underwent thymectomy on days 1, 3, or 7 after the initial intrathymic injection of alloantigen and intraperitoneal ALS. Twenty-one days after intrathymic alloantigen injection and ALS, all rats underwent transplantation with a heterotopic LEW cardiac allograft. RESULTS: Thymectomy performed 1 (mean survival time, 6.8 days) and 3 (mean survival time, 8.0 days) days after donor alloantigen injection and ALS did not affect the normal rejection of LEW cardiac allografts. In contrast, thymectomy 7 days after intrathymic alloantigen injection and ALS resulted in indefinite survival of cardiac allografts in 75% of recipients (mean survival time > 77.0 days). In addition, allospecific cytotoxic T lymphocyte activity and interleukin-2 production were markedly decreased in those recipients undergoing thymectomy after 7 days compared with untreated control rats and recipients undergoing thymectomy 1 and 3 days after alloantigen injection. CONCLUSIONS: The presence of the thymus for at least 7 days after intrathymic alloantigen injection and intraperitoneal ALS allows the development of indefinite donor-specific cardiac allograft tolerance. PMID- 8342126 TI - Biochemical detection of small intestinal allograft rejection by elevated circulating levels of serum intestinal fatty acid binding protein. AB - BACKGROUND: Intestinal fatty acid binding protein (I-FABP) was investigated as a serum marker for acute intestinal allograft rejection. Its behavior was compared with that of another putative marker of intestinal damage, hexosaminidase. METHODS: Transplants were performed in three groups of rats: group 1, Lewis to Lewis; group 2, ACI to Lewis, no immunosuppression; and group 3, ACI to Lewis with cyclosporine given on posttransplant days 0 through 5. Daily serum I-FABP and hexosaminidase levels were quantitated and serial graft biopsy specimens were obtained. RESULTS: Serum I-FABP levels fell to 20 ng/ml or less in all animals between posttransplant days 3 and 4. In group 1, I-FABP levels remained at baseline throughout the experiment. In group 2, I-FABP levels rose dramatically on either day 6 or 7 and declined to baseline within 4 days of the peak. On the day that I-FABP levels increased, findings of biopsy specimens were consistent with early rejection. In group 3 the rise in serum I-FABP levels was delayed 2 to 10 days. Hexosaminidase did not correlate with rejection. CONCLUSIONS: Serum I FABP content correlated with early histologic manifestations of rejection. Hexosaminidase was insensitive as a marker in this model. I-FABP, which has a human analog, has potential as a biochemical marker for early intestinal allograft rejection. PMID- 8342125 TI - Endotoxin stimulates arginine transport in pulmonary artery endothelial cells. AB - BACKGROUND: The pulmonary endothelium plays an important role in the metabolism of the amino acid arginine, the exclusive precursor molecule for nitric oxide (NO). Despite decreased circulating arginine levels, endothelial NO production is elevated during endotoxemia. However, the regulation of pulmonary artery endothelial arginine transport has not been studied. We hypothesized that endotoxin stimulates carrier-mediated arginine transport by the pulmonary endothelium. METHODS: The relative contributions of the various transport systems to total arginine transport by porcine pulmonary artery endothelial cells (PAECs) was determined by assaying the uptake of 3H-L-arginine in the presence or absence of Na+. PAECs were then incubated with various concentrations of Escherichia coli endotoxin, and y(+)-mediated arginine transport was measured at different time points thereafter. Kinetic studies were performed over a range of arginine concentrations to determine changes in transport affinity and maximum rate of metabolism. To address the role of RNA and protein synthesis in the increased transport, uptake was measured after exposure of cells to the transcriptional inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide. RESULTS: Most (75%) of arginine transport by PAECs was mediated by the high affinity Na(+)-independent transport system y+. Endotoxin stimulated y(+) mediated arginine transport by PAECs twofold to fivefold, a response that was time and dose dependent. The accelerated transport was detectable within 2 hours and maximal at 12 hours. Kinetic studies revealed that the accelerated arginine transport was the result of a 68% increase in the maximal transport velocity (1519 +/- 65 pmol/mg protein/30 sec in endotoxin-treated cells vs 903 +/- 96 in control cells; p < 0.01) without a change in transport affinity. The endotoxin mediated increase in arginine uptake was abrogated by actinomycin D and cycloheximide. CONCLUSIONS: Endotoxin stimulates Na(+)-independent arginine transport by PAECs through a process that requires de novo RNA and protein synthesis, possibly of the transporter itself. This response may be designed to support arginine-dependent biosynthetic pathways in the lung during septic states. PMID- 8342127 TI - Composite kidney-islet transplantation prevents recurrent autoimmune beta-cell destruction. AB - BACKGROUND: Clinically successful islet transplantation has been rare despite adequate isolation techniques. Reenactment of the original autoimmune beta-cell destruction may contribute to the poor results. Distinguishing autoimmune effects from rejection can be accomplished with isogeneic transplants exchanged between diabetes-prone (BB-DP) and diabetes-resistant (BB-DR) rats. These experiments determine the relative sensitivity of islet, whole pancreas, and composite kidney islet transplants to recurrent autoimmunity. METHODS: Acutely diabetic (BB-Ac) BB rats served as recipients of vascularized pancreas, intraportal (IPo) or renal capsular (KC) islet transplants, or vascularized composite kidney-islet grafts from BB-DR or BB-DP donors. Graft function was assessed by daily blood glucose level, and the outcome was confirmed on histologic examination. Cyclosporine 5 mg/kg/day intramuscularly was administered to assess its effect on recurrent beta cell injury. RESULTS: BB-DP pancreases developed recurrent autoimmunity in 55% of cases; cyclosporine afforded complete protection if maintained. Diabetes resistance was transplanted with 23 of 23 BB-DR pancreas grafts; however, islet isolation led to a loss of diabetes resistance for islet grafts to the KC and IPo. Cyclosporine protected KC but not IPo islets. Composite BB-DR kidney-islet transplants functioned indefinitely in all cases. CONCLUSIONS: Transplanted islets initially survive by passive diffusion but are ultimately revascularized by capillary ingrowth. The finding that composite kidney-islet transplants function indefinitely suggests that the revascularizing endothelium may play a role in resistance or susceptibility to autoimmune beta-cell destruction. PMID- 8342128 TI - T-cell recognition of ovarian cancer. AB - BACKGROUND: The existence of a tumor-specific T-cell immune response to human malignant melanoma has been well documented. In contrast, the existence of tumor specific cytotoxic T lymphocyte to ovarian cancer remains controversial despite the abundant lymphocytic infiltrates in the malignant ascites and solid tumor of these patients. METHODS: Tumor-associated lymphocytes (TAL) from the malignant ascites and tumor-infiltrating lymphocytes (TIL) from the solid tumors were isolated from six untreated patients with ovarian cancer. TAL and TIL were grown with initial anti-cluster of differentiation of T cells (CD3), low-dose interleukin-2, and tumor stimulation. T-cell lines were analyzed in functional studies. RESULTS: At 5 weeks, TAL and TIL from five of six patients were > 50% CD8+, and one of six was > 70% CD4+. In all five pairs of CD8 positive cultures, both TAL and TIL exhibited high levels of tumor-specific cytotoxicity for ascite and solid tumor, respectively. T-cell recognition of tumor was mediated through the T-cell receptor-CD3 complex and was human leukocyte antigen class I restricted. TAL and TIL lysed autologous ascitic tumor equally well; however, TAL mediated tumoricidal activity against autologous solid tumor was consistently and significantly poorer than TIL-mediated killing. CONCLUSIONS: Tumor-specific cytotoxic T lymphocytes can be expanded from both TAL and TIL. However, TAL do not kill solid tumor as efficiently as TIL. This suggests the requirement of TIL, or a combination of TIL and TAL, for effective immunotherapy. PMID- 8342129 TI - Soluble factors modulate changes in collagen gene expression in abdominal aortic aneurysms. AB - BACKGROUND: Although increased procollagen gene expression and synthesis have been implicated in the progression of abdominal aortic aneurysms (AAA), factors modulating this change have not been identified. Furthermore, it is not known whether the increase in AAA procollagen expression is specific to this disease or also occurs in tissue affected by atherosclerotic occlusive disease (AOD). If paracrine rather than autocrine factors are responsible for increased gene expression in AAA, this effect should be transferable to target smooth muscle cells through conditioned media. Our objectives were to determine 1 alpha (I) procollagen messenger RNA levels in AOD tissue compared with normal and AAA and to determine whether differences noted in tissue procollagen gene expression could be transferred through conditioned media from normal, AOD, and AAA tissues to target smooth muscle cells in primary culture. METHODS: Normal, AOD, and AAA tissue was used for tissue RNA extraction or was minced and washed with serum free media (4 degrees C) x 30 minutes and the media applied to human aortic smooth muscle cells (SMC) in primary culture for 36 hours. Total RNA from tissue and SMC exposed to conditioned media was analyzed by Northern and dot blot analysis for 1 alpha (I) procollagen. RESULTS: Relative tissue 1 alpha (I) procollagen levels were not increased in AOD (0.23 +/- 0.05) as compared with normal (0.17 +/- 0.03); both were decreased compared with AAA (0.53 +/- 0.07; p < 0.01). The 1 alpha (I) procollagen levels in SMC exposed to conditioned media from AAA (1.73 +/- 0.15) were increased (p < 0.05) compared with AOD (1.10 +/- 0.12) and normal (1.16 +/- 0.16). CONCLUSIONS: There is no increase in tissue AOD procollagen gene expression. The ability to transfer the same relative patterns of gene expression from tissue to target SMC with conditioned media suggests that paracrine, rather than autocrine, factors modulate procollagen expression in AAA tissues. PMID- 8342130 TI - Regression of intimal hyperplasia with restoration of endothelium-dependent relaxing factor-mediated relaxation in experimental vein grafts. AB - BACKGROUND: The reversibility of the morphologic and functional alterations that occur in veins transplanted into the arterial circulation was examined in this study. METHODS: Common carotid vein bypass grafts (VG) were performed in 20 male New Zealand White rabbits. Ten VG and jugular veins (CV) were harvested after 14 days, and ten VG were reimplanted as venovenous bypass grafts (REV) and harvested after an additional 14 days. Vessels were taken for structural or isometric tension studies to norepinephrine, serotonin, and bradykinin and to acetylcholine and sodium nitroprusside after precontraction. RESULTS: There was a decrease in the thickness of the intima (p = 0.02) and the media (p = 0.002) in REV compared with VG. In REV, sensitivity to norepinephrine decreased (p = 0.0007) with a reduced maximal tension to norepinephrine (p = 0.02) and to serotonin (p = 0.0001). Bradykinin sensitivity increased in REV (p = 0.003 vs VG) and was greater than in CV. Only the precontracted CV and REV relaxed to acetylcholine. All tissues relaxed to sodium nitroprusside. CONCLUSIONS: This study suggests that intimal hyperplasia can be reversed with restoration of endothelium dependent relaxing factor-mediated relaxation but that only a partial regression of the contractile abnormalities can be achieved. PMID- 8342131 TI - Interleukin-1 receptor antagonist improves survival and preserves organ adenosine 5'-triphosphate after hemorrhagic shock. AB - BACKGROUND: This study was designed to determine the role of interleukin-1 (IL-1) in hemorrhagic shock death. METHODS: Pentobarbital anesthetized C3H/HeN mice (n = 59) were prepared with a femoral arterial catheter and were randomized to treatment with an IL-1 receptor antagonist (IL-1ra, 10 mg/kg, n = 29) or an equal volume of phosphate-buffered saline solution (vehicle, n = 30) by subcutaneous bolus injection at 15 minutes before hemorrhage and again at 120 minutes. Continuous posthemorrhage delivery of IL-1ra or vehicle was performed in each group (1.5 mg IL-1ra in 30 microliters/day) through a subcutaneous osmotic pump. Rapid hemorrhage of 4 ml/100 gm weight was followed by normal saline resuscitation of 12 ml/100 gm 60 minutes later. RESULTS: Survival analysis by Wilcoxon rank sum analysis revealed a significantly improved 5-day survival in IL 1ra-treated mice (n = 15, 20%) as compared with vehicle-treated mice (n = 14, 6%, p < 0.001). To determine a possible mechanism of this survival advantage, the remaining mice in each treatment group were killed at 30 minutes to obtain blood and tissue samples from the heart, liver, and kidney for measurement of adenosine 5'-triphosphate (ATP). No difference in hematocrit, circulating neutrophils, or levels of glucose, lactate, or tumor necrosis factor was identified between groups to explain the improved outcome. IL-1ra prevented hemorrhage-induced ATP depletion observed in vital organs of vehicle-treated mice. CONCLUSIONS: The data implicate IL-1 in shock-induced ATP depletion and suggest IL-1ra may improve hemorrhagic shock survival by preventing ATP depletion in vital organs. PMID- 8342132 TI - Erythromycin, motilin, and the esophagus. AB - BACKGROUND: Motilin induces phase III activity of the gastroesophageal tract. Erythromycin has a motilin-like effect on the stomach, but possible esophageal effects have not been evaluated and are the focus of our investigation. METHODS: Esophageal manometry was performed in 11 healthy volunteers before and after intravenous infusion of 500 mg erythromycin. Values are expressed as means +/- SEM. RESULTS: Lower esophageal sphincter (LES) pressure increased from 21.1 +/- 2.6 mm Hg at baseline to 37.5 +/- 3.8 mm Hg after erythromycin infusion (p < 0.0001). Erythromycin did not affect LES length, esophageal body contraction amplitude, duration or velocity, or the upper esophageal sphincter. Serum motilin levels decreased from 96.4 +/- 10.9 pmol/L to 81.8 +/- 10.9 pmol/L (p < 0.01) after erythromycin administration. CONCLUSIONS: Erythromycin profoundly stimulates the normal human LES. This is a direct motilin agonist-like effect and is not mediated by release of endogenous motilin. Erythromycin has no important effect on the esophageal body or the upper esophageal sphincter. PMID- 8342133 TI - Ca2+ calmodulin regulates basal gallbladder absorption. AB - BACKGROUND: Gallbladder absorption is altered during gallstone formation, a phenomenon that may be partly the result of elevated biliary Ca2+ levels. Recent studies suggest that changes in gallbladder absorption are mediated by intracellular Ca2+ ([Ca2+]ic). However, the mechanisms by which [Ca2+]ic regulates gallbladder ion transport are not known. Calmodulin is a Ca2+ receptor protein in the Ca2+ messenger system that modulates ion transport in the small intestine. We hypothesized that Ca(2+)-calmodulin mediates the effects of [Ca2+]ic on gallbladder absorption. METHODS: Prairie dog gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded. Unidirectional Na+, Cl-, and water fluxes were measured before and after mucosal exposure to 5 x 10(-5) mol/L trifluoperazine, a potent calmodulin antagonist. In addition, the ion transport effects of increased extracellular calcium and theophylline were determined in the presence of calmodulin inhibition. RESULTS: Inhibition of calmodulin resulted in an increase in net Na+ and water absorption and converted the gallbladder from a Cl- absorptive state. Similar results were obtained during exposure to two other calmodulin antagonists that differ only in their affinity for calmodulin but not in their hydrophobicity, suggesting that the observed changes were caused by specific calmodulin inhibition. Effects of trifluoperazine were reversed by increasing luminal [Ca2+] or theophylline exposure. CONCLUSIONS: The effects of calmodulin inhibition are directly opposite of the effects of the Ca2+ ionophore. We conclude that Ca(2+)-calmodulin regulates gallbladder absorption at basal [Ca2+]ic. Further studies are needed to determine whether altered calmodulin activity is responsible for increased gallbladder absorption during gallstone formation. PMID- 8342134 TI - Platelet-activating factor-induced polymorphonuclear neutrophil priming independent of CD11b adhesion. AB - BACKGROUND: Our previous studies have implicated phospholipase A2-dependent platelet-activating factor (PAF) production in the genesis of polymorphonuclear neutrophil (PMN)-mediated tissue injury after gut ischemia-reperfusion. Further, these studies have suggested a discordance of PMN sequestration and tissue injury. CD11B-dependent PMN-endothelial cell adhesion has been purported to play a dominant role in PMN-mediated tissue injury. We therefore undertook this study with the hypothesis that PAF-induced PMN superoxide production requires CD11B mediated PMN-endothelial cell adherence. METHODS: Human PMNs, isolated by Percoll gradient centrifugation, were exposed to PAF (10 ng/ml). At fixed times of exposure during 120 minutes, (1) superoxide production, (2) CD11B receptor expression, and (3) PMN adhesion to unstimulated human umbilical vein endothelial cell cultures were assayed. RESULTS: PAF induced prompt changes in PMN priming (increased superoxide production after N-formyl-methyl-leucyl-phenylalanine activation), adhesion to unstimulated endothelial cells, and CD11B receptor expression. Priming was temporally concordant with the rise and fall of CD11B expression but appeared to precede adhesion. CD11B blockade (F(Ab') 2 anti-CD11B [60.1] antibodies), before or at maximal PAF priming, reduced PMN adhesion but had no effect on superoxide production. CONCLUSIONS: In summary, PAF-induced PMN priming occurs in temporal concordance with the expression of CD11B and subsequent endothelial cell adherence, but CD11B-mediated adherence is not essential for this process. PMID- 8342135 TI - Use of an Objective Structured Clinical Examination (OSCE) to measure improvement in clinical competence during the surgical internship. AB - BACKGROUND: Traditional ward ratings and multiple-choice tests do not reliably assess clinical competence. This study determined the reliability of the Objective Structured Clinical Examination (OSCE) and its sensitivity in detecting the performance gains and deficits in surgical interns. METHODS: A comprehensive 35-station OSCE was administered to 23 incoming interns and seven outgoing interns. The OSCE comprised 17 two-part clinical problems, relying primarily on actual or simulated patients. The reliability of the examination was assessed by coefficient alpha. Significant differences in performance between the two intern groups, between parts A and B, and among the 17 problems were determined by a three-way ANOVA: OSCE performance was also correlated with National Board of Medical Examiners Part II scores. RESULTS: The reliabilities of part A, part B, and parts A and B combined were 0.72, 0.70, and 0.82, respectively. Overall, the outgoing interns performed significantly better than the incoming interns: 58% +/ 1% mean OSCE score versus 47% +/- 1% (p = 0.0001). The 17 clinical problems differed significantly in difficulty; major performance deficits were seen in both groups of trainees. The correlation of OSCE scores with National Board of Medical Examiners Part II scores was not significant (r = 0.11, p = 0.633). CONCLUSIONS: We conclude that the OSCE is an innovative, reliable tool for evaluating resident competence. Although outgoing interns performed better than did incoming interns, the OSCE scores clearly indicated major performance deficits in all interns. PMID- 8342137 TI - PDGF and FGF reverse the healing impairment in protein-malnourished diabetic mice. AB - BACKGROUND: Growth factors have been shown to improve healing in impaired models but not after malnutrition. The effects of growth factors on altered tissue repair caused by malnutrition were examined. METHODS: Nondiabetic and diabetic mice fed a 1% protein diet received full-thickness skin wounds. Wounds were treated topically with vehicle, platelet-derived growth factor (PDGF, 10 micrograms) or basic fibroblast growth factor (bFGF, 1 microgram), for 5 days. RESULTS: Malnourished animals developed significantly impaired wound closure. PDGF or bFGF did not enhance closure in nondiabetic C57BL/KsJ-db/m mice, whether fed normal or restricted diets. The same treatment regimen was effective in reversing the delayed wound closure in their genetically diabetic C57BL/KsJ-db/db littermates. The growth factors significantly enhanced tissue repair in diabetic mice fed a 1% protein diet starting as early as day 15 and continuing until day 21. Protein-depleted diabetic wounds had significantly decreased cellularity and granulation tissue formation. These deficiencies were reversed with growth factor treatment. CONCLUSIONS: Despite the lack of effects in nondiabetic animals, growth factors improve healing in diabetic mice with restricted protein intake. The differential effects may result from different healing mechanisms: nondiabetic animals heal mainly by contraction; diabetic animals require granulation tissue formation and reepithelialization. PMID- 8342136 TI - Pentoxifylline restores cardiac output and tissue perfusion after trauma hemorrhage and decreases susceptibility to sepsis. AB - BACKGROUND: Although pentoxifylline produces various beneficial effects in a preheparinized model of hemorrhagic shock, it was unknown whether this agent restores the depressed cardiac output (CO) and tissue perfusion in a nonheparinized model of trauma-hemorrhage and resuscitation and, if so, whether it decreases the susceptibility to sepsis after hemorrhage. METHODS: After laparotomy (i.e., induction of trauma), rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate. The animals were then resuscitated with Ringer's lactate, four times the volume of shed blood. Pentoxifylline (50 mg/kg body weight) or normal saline solution was infused intravenously more than 95 minutes during and after resuscitation. At 1.5 and 4 hours after resuscitation, CO, tissue perfusion, and plasma liver enzyme levels were determined. Sepsis was induced by cecal ligation and puncture at 20 hours after hemorrhage, and the necrotic cecum was excised 10 hours thereafter. RESULTS: CO and tissue perfusion in the liver, kidney, spleen, and small intestine decreased significantly after hemorrhage and resuscitation. Pentoxifylline treatment, however, restored the depressed CO and tissue perfusion. The elevated liver enzyme levels were also significantly reduced by pentoxifylline treatment. Moreover, pentoxifylline prevented the increased mortality of posthemorrhaged rats subjected to sepsis. CONCLUSIONS: Because pentoxifylline restored the depressed CO and tissue perfusion and decreased the susceptibility to sepsis, this agent appears to be a useful adjunct to crystalloid resuscitation after trauma and hemorrhage, even in the absence of blood resuscitation. PMID- 8342138 TI - Tissue generation with growth factors. AB - BACKGROUND: An in vivo experimental model was introduced to determine whether the mitogenic effect of recombinant platelet-derived growth factor (rPDGF) could be used to generate potentially useful tissue. METHODS: In Lewis rats, the extended femoral arteriovenous bundle was placed within silicone chambers containing collagen disks. The disks could deliver their content of rPDGF-BB (125 to 131 micrograms/disk) either as a rapid pulse or as a slow release. The time course of tissue generation was determined by harvesting the specimens at various postoperative days. The effect of continuous versus pulsed delivery was determined at 30 days. Analysis of the generated tissue was performed by use of histomorphometry. RESULTS: Pulsed delivery of rPDGF-BB induced the formation of a substantial amount of tissue that peaked at 10 to 15 days (145.9 +/- 13.8 vs 35.0 +/- 6.8 mm3, p < 0.0001); however, the generated tissue completely subsided by day 30. Sustained delivery of rPDGF-BB caused continuous growth of the tissue and was more effective than pulsed delivery. CONCLUSIONS: In an experimental model that approximates an in vivo tissue culture system, rPDGF-BB can induce a tenfold increase in tissue within the chamber. However, that tissue is labile and its survival necessitates continuous rPDGF-BB delivery. To become useful for reconstructive purposes, means to stabilize this new tissue growth are needed. PMID- 8342139 TI - The effects of CO2 pneumoperitoneum on hemodynamics in hemorrhaged animals. AB - BACKGROUND: Carbon dioxide (CO2), the primary gas currently used for pneumoperitoneum, has been known to cause systemic effects on acid-base balance and hemodynamic stability. We studied the hemodynamic effects of CO2 pneumoperitoneum in a hemorrhagic shock model to assess the safety of laparoscopic procedures in acute trauma patients. METHODS: After 1 hour of baseline, 32 anesthetized adult pigs were randomized into four groups. Group 1 animals had no hemorrhage, serving as a control group. Group 2 animals had a mild hemorrhage of 10 ml/kg/hr. Group 3 animals had a moderate hemorrhage of 20 ml/kg/hr. Group 4 animals had a moderate hemorrhage but were resuscitated with 40 ml/kg of lactated Ringer's solution. All animals were then insufflated to an intraabdominal pressure of 15 mm Hg with CO2 gas for 1 hour. The abdomen was then decompressed, and the animals were observed for another hour. All animals survived hemorrhage. One death each occurred in moderate hemorrhage groups, both near the end of CO2 pneumoperitoneum. These animals were not included in statistical analysis. RESULTS: In euvolemic animals, CO2 pneumoperitoneum induced hypercapnia (from 34 +/- 1 mm Hg to 48 +/- 1 mm Hg), acidemia (from 7.45 +/- 0.02 to 7.36 +/- 0.02), and a 20% reduction in stroke volume. Mild hemorrhage and CO2 insufflation resulted in a similar degree of acidemia (7.35 +/- 0.01), but moderate hemorrhage and CO2 insufflation led to more severe acidemia (7.26 +/- 0.02). Fluid resuscitation failed to prevent this severe fall in pH (7.30 +/- 0.03) for group 4. PaCO2 was not affected by hemorrhage, but CO2 pneumoperitoneum induced significant hypercapnia in all groups, ranging from 48 +/- 1 mm Hg for euvolemic animals to 52 +/- 1 mm Hg for moderate hemorrhage animals. Stroke volume declined as a function of blood loss, and it was further depressed by CO2 insufflation, to as low as 75% of baseline in mild hemorrhage and 55% of baseline in moderate hemorrhage. Both stroke volume and cardiac index initially responded to large-volume fluid replacement after moderate hemorrhage but quickly decreased to levels comparable to those of unresuscitated animals when CO2 pneumoperitoneum was created. CONCLUSIONS: Intraperitoneal insufflation with CO2 for diagnostic laparoscopy may be hazardous in acute hypovolemic trauma patients. PMID- 8342140 TI - Pulmonary function after laparoscopic cholecystectomy. AB - BACKGROUND: The purpose of this study was to prospectively compare the effect of laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC) on postoperative pulmonary function. METHODS: Forty consecutive patients (20 in each group) who were evenly matched in terms of pulmonary risk factors were assigned to either elective LC or OC. Pulmonary function studies, oxygen saturation, and chest radiography were performed on both groups before and after the operation until baseline levels were reached. Narcotic requirements and pulmonary complications were compared. The t test, ANOVA, and chi-squared analysis were used. RESULTS: Compared to the patients who underwent OC, patients who underwent LC had a significant reduction in postoperative pulmonary impairment (30% to 38%) in all areas studied including forced vital capacity; forced expiratory volume in 1 second; forced expiratory flow, mid-expiratory phase; maximum forced expiratory flow; maximum voluntary ventilation; total lung capacity; and oxygen saturation. Pulmonary function returned to baseline levels 4 to 10 days sooner after LC. Pulmonary complications including atelectasis and hypoxia were less frequent after LC. An eight-fold decrease was noted in postoperative pain medication requirement in the LC group. CONCLUSIONS: Compared to OC, laparoscopic cholecystectomy results in a significantly reduced compromise in pulmonary function and narcotic requirement leading to fewer postoperative pulmonary complications. Laparoscopic cholecystectomy should be considered the procedure of choice for elective cholecystectomy. PMID- 8342141 TI - Lateral hypothalamic dopaminergic neural activity in response to total parenteral nutrition. AB - BACKGROUND: The lateral hypothalamic dopaminergic neurons dominate modulation of food intake. Changes in lateral hypothalamic synaptic dopaminergic release before and during total parenteral nutrition (TPN) and its components were measured in vivo with microdialysis probes. METHODS: Rats had an intracerebral guide cannula and an internal jugular catheter placed. Ten days after recovery, rats were fasted for 24 hours. A 2 mm microdialysis probe was inserted into the lateral hypothalamus neurons via the guide cannula. Dopamine level was measured by high performance liquid chromatography in three 60-minute baseline dialysis samples. TPN, glucose, fat, or amino acid was then infused via the internal jugular catheter, and dopamine level was measured in three more 60-minute dialysate samples. Single nutrients were infused for 24 hours, and dopamine was measured during the 3 hours after the infusions were stopped. Data were analyzed by paired t test (mean +/- standard error) and represented percentage change from baseline. RESULTS: Dopamine levels rose significantly (p < 0.05) and remained so during infusions in TPN (26% +/- 3%), glucose (26.5% +/- 4.6%), fat (36.2% +/- 6.7%), and amino acids (9.6% +/- 4.2%). After infusions were stopped, dopamine levels decreased to -35.4% +/- 1.5% in glucose but remained unchanged with fat and amino acids. CONCLUSIONS: Increase in lateral hypothalamic dopamine level occurs with TPN and its components, and changes persist temporarily after stopping the infusions, explaining in part the slow recovery of food intake after TPN is stopped. PMID- 8342142 TI - Molecular mechanisms of decreased interleukin-2 production after thermal injury. AB - BACKGROUND: Among the fundamental immunologic abnormalities induced by serious traumatic or thermal injury are alterations in T cell activation, reduced lymphocyte interleukin-2 (IL-2) production, and associated depression of T lymphocyte proliferation. This study attempts to localize the cellular mechanisms underlying abnormal IL-2 production in thermal injury. METHODS: Following National Institutes of Health guidelines, 150 A/J mice were anesthetized, subjected to a 20% full-thickness scald burn injury or sham burn, and killed at intervals from 4 to 21 days later; splenocytes were harvested for in vitro studies. For measurement of IL-2 production, cells were cultured with either concanavalin A or a combination of the phorbol ester PMA, which directly activates protein kinase C, and the calcium ionophore A23187, which increases intracellular calcium. Cytokine mRNA expression was measured by Northern blot analysis and IL-2 production by bioassay. RESULTS: Both IL-2 production and IL-2 mRNA expression were consistently suppressed in concanavalin A-stimulated cells from burned mice compared with sham burns. This suppression of IL-2 and IL-2 mRNA also occurred when T cells were activated with PMA and A23187, bypassing the earlier stages of the signal transduction mechanism. IL-1 beta and tumor necrosis factor-alpha mRNA expression were consistently increased in burned animals, indicating that decreased IL-2 mRNA expression was specific to IL-2 and not representative of a global decrease in cytokine mRNA expression. CONCLUSIONS: These results suggest that the principal cellular abnormalities that result in altered T cell activation and IL-2 production after thermal injury lie downstream of the initiating signal transduction events and before IL-2 gene transcription. PMID- 8342143 TI - Cultured keratinocyte allografts fail to induce sensitization in vivo. AB - BACKGROUND: The use of cultured keratinocyte (CK) allografts for burn wounds offers a potentially unlimited supply of skin. It is unknown, however, whether CK allografts induce rejection in vivo. This study investigated the induction of immune responsiveness to CK allografts as measured by mixed lymphocyte response and serum cytotoxic antibody. METHODS: Female CBA mice (n = 160) were randomized to four equal groups, each receiving a 3 cm2 flank graft of autologous CBA CK (Auto CK), allogeneic C57BL/6 CK (Allo CK), C57BL/6 full thickness skin (Allo FT), or Sham. Graft take was assessed by gross and histologic examinations. Unidirectional mixed lymphocyte response was measured with graft recipient and donor splenocytes by use of tritiated thymidine uptake. Stimulation indexes were calculated. Serum cytotoxic antibody was measured by coculturing graft recipient serum with donor splenocytes and rabbit complement and assessing resultant cell killing. RESULTS: Overall graft take was 50% for Allo CK and 74% for Auto CK, Allo FT, but not Allo CK, were associated with significantly increased stimulation indexes compared with Auto CK and Sham (p < 0.01). Allo FT, but not Allo CK, resulted in elevated titers of alloantibody, reaching significant levels 10 days after grafting (p < 0.05). CONCLUSIONS: CK allografts do not result in increased in vitro T cell responses or enhanced alloantibody formation, indicating that sensitization to major histocompatibility antigens by CK does not occur. These data suggest that CK allografts may provide a possible source of grafts for victims of large burn wounds. PMID- 8342144 TI - Intercellular communication and maintenance of islet cell mass--implications for islet transplantation. AB - BACKGROUND: The major emphasis in islet transplantation has been the development of methods to enhance islet purity. This focus assumes that islets do not require support from other cellular elements of the pancreas. We chose to examine a possible duct-islet interaction because of the embryologic origin of islets from ductal epithelium. METHODS: Duct and islet cells were prepared by collagenization of hamster pancreas and purified on a bovine serum albumin gradient. Primary duct cultures were passaged twice. Duct-conditioned medium was collected from the tertiary cultures. Three groups of cultures were established: group 1, 100 islets/plate in minimal medium (Dulbecco's modified Eagle medium/F12); group 2, 100 islets + 40 duct fragments/plate in Dulbecco's modified Eagle medium/F12; and group 3, 100 islets/plate+duct-conditioned medium. After a 3-day incubation, tritiated thymidine (1 microCi/ml) was added for 24 hours. The islets were separated from the ducts by handpicking and then sonicated. DNA was measured (microgram) fluorometrically and tritiated thymidine incorporation, a measure of cell proliferation, was determined in trichloroacetic acid-precipitated material by liquid scintillation. Data (mean +/- SEM) were compared by two-tailed Student's t test. RESULTS: Tritiated thymidine incorporation into islet cells in minimal medium (81.1 +/- 24.6 disintegrations per minute [dpm]/microgram DNA [n = 8 plates]) was less than 25% (p < 0.001) of that of islet cells cocultured with ducts (323.2 +/- 54.5 dpm/micrograms DNA [n = 6]) or with duct-conditioned medium (389.7 +/- 27.6 dpm/micrograms DNA [n = 5]). CONCLUSIONS: Pancreatic duct epithelium can stimulate islet cell proliferation in a paracrine manner. PMID- 8342145 TI - The effect of cocaine on the physiologic response to hemorrhagic shock. AB - BACKGROUND: Bradycardia is thought to be an uncommon and abnormal response to acute blood loss. A review of trauma patients (n = 84) admitted during a 1-year period with a systolic blood pressure of less than 100 mm Hg revealed that 45% had relative bradycardia (heart rate < 100 beats/minute). Cocaine use was recorded more often in this group (76% versus 26%; p < 0.05) compared with patients with tachycardia (heart rate > or = 100 beats/minute). We investigated the effect of cocaine use on the response to acute blood loss in an animal model of hemorrhagic shock. METHODS: Rats were given intraperitoneal cocaine 20 mg/kg/day for 14 days (n = 10) or saline solution (n = 10). The rats were bled until 30% of their blood volume was shed; they were resuscitated 30 minutes later. RESULTS: Cocaine-treated rats showed a decreased 24-hour survival rate (50% versus 100%; p < 0.05), a relative bradycardic response compared to baseline heart rate (-8.9% +/- 6.4% versus 7.5% +/- 3.5%; p < 0.05), and a greater drop in mean arterial blood pressure (-55.5% +/- 4.8% versus -37.0% +/- 5.5%; p < 0.05) by 5 minutes of shock. Cocaine-treated rats were more acidotic after shock compared to controls (pH 7.36 +/- 0.03 versus 7.44 +/- 0.02; p < 0.05). CONCLUSIONS: Cocaine had a deleterious effect on experimental hemorrhage. The bradycardic response observed in our trauma patients may be due, in part, to cocaine abuse, and we postulate that chronic cocaine use alters the normal adrenergic response to blood loss. PMID- 8342146 TI - The ivory tower from outside and in: a survey of Minnesota surgeons. AB - BACKGROUND: Increasing competition has eroded the patient base of many university hospitals and may jeopardize their teaching programs. METHODS: We questioned all private surgeons (PS), university surgeons (US), and resident surgeons (RS) in our state. Chi-squared analysis was used. RESULTS: Most PS, US, and RS, respectively, answered "yes" when asked to respond to the following items: whether teaching hospitals were the best way to educate new surgeons (77% versus 96% versus 87%), whether surgery residencies should be based at a university hospital (72% versus 96% versus 91%), and whether PS should refer complicated clinical cases for teaching purposes (75% versus 87% versus 68%). Differences appeared when the groups were asked whether the university should take the lead in guaranteeing the quality of surgical care in the state (67% versus 100% versus 77%, p = 0.002) and whether PS are better teachers of surgery than US (40% versus 4% versus 59%, p = 0.0001). An unexpected and disturbing trend was observed in RS when groups were asked whether practicing surgeons had any obligation to the state's university (57% versus 74% versus 22%, p = 0.0001) and whether surgeons had an obligation to repay society for their education (77% versus 83% versus 56%, p = 0.005). CONCLUSIONS: Despite recent changes in medical economics, most PS still feel residency programs should be university based. A significantly smaller percentage of RS feel an obligation to their university and to society than do either PS or US. PMID- 8342147 TI - Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function. AB - BACKGROUND: The purpose of this study was to determine whether morphologic and functional changes in intestinal smooth muscle occur after small bowel transplantation (SBTx) and during chronic rejection. METHODS: Orthotopic SBTx was performed in syngeneic (ACI-ACI, n = 6) and allogeneic (ACI-Lewis, n = 6) rat strain combinations. The latter received temporary immunosuppression (cyclosporine 15 mg/kg/body weight on postoperative days 0 to 6 once a day, postoperative days 7 to 28 every other day), which led to clinically quiescent chronic rejection of the graft by 90 days after SBTx. At that time structure and function of the jejunal muscularis externa were evaluated with histochemistry, mechanical organ bath, and intracellular electrical recording techniques. RESULTS: Histochemistry showed a 1.5-fold thickening of the intestinal muscularis externa of syngeneic grafts, although contractile properties and intracellular electrical activity were not significantly different from controls. Allogeneic, chronically rejecting grafts showed a threefold increase in the thickness of the muscularis externa as a result of both smooth muscle hyperplasia and hypertrophy. Muscle strips from chronically rejecting grafts generated only 23% of the maximal contractile force generated by controls (bethanechol 300 mumol/L). Median effective concentration and threshold values were not significantly different. Intracellular electrical activity of circular smooth muscle cells revealed a significantly more depolarized resting membrane potential and a reduction in slow wave amplitude compared with controls. CONCLUSIONS: Syngeneic SBTx resulted in a significant thickening of the muscularis externa with an apparent adaptation to control in vitro physiologic function. Allogeneic SBTx subject to chronic rejection leads to profound morphologic changes and functional impairments. Changes in muscle structure and function evolve before the clinical signs of graft rejection. PMID- 8342148 TI - Gs alpha--identification of a gene highly expressed by insulinoma and other endocrine tumors. AB - BACKGROUND: The isolation of mRNA molecules that are either uniquely or more highly expressed by tumor and not normal tissue is a powerful tool in the study of cell regulation and growth. To this end we constructed a complementary DNA (cDNA) library from messenger RNA (mRNA) isolated from a human insulinoma and, by differential hybridization with cDNA from both normal pancreas and insulinoma, isolated clones more highly expressed by insulinoma. METHODS: Total RNA was isolated from human insulinoma and normal pancreas and purified to mRNA by oligo (dT) column. An insulinoma cDNA library was constructed and screened with 32P labeled cDNA from pancreas and insulinoma. Northern blots from insulinoma, pancreas, carcinomas, normal endocrine tissues, and endocrine tumors were then probed with the 32P-labeled inserts. RESULTS: Two clones that consistently hybridized with 32P cDNA from insulinoma and not pancreas proved to represent mRNAs for insulin and the alpha subunit of the Gs protein. There was a markedly higher expression (30-fold) of the gene for Gs alpha in mRNA from insulinoma compared with normal pancreas by Northern blot analysis. We found Gs alpha to be more highly expressed by a pheochromocytoma, a corticotropin-producing islet cell tumor of the pancreas, and a corticotropin-producing thymic carcinoid (up to 35 fold) compared with normal pancreas, whereas normal endocrine tissues, a parathyroid adenoma, thyroid follicular adenoma, gastrinoma, and several carcinomas showed no expression. CONCLUSIONS: This study showed that Gs alpha is highly expressed in insulinoma and certain endocrine tumors. It is not expressed in several cancers or normal endocrine tissues. Others have implicated mutated Gs proteins in the tumorigenesis of pituitary and thyroid tumors. G proteins are also known to mediate hormonal transmembrane signaling. Its overexpression in four of seven endocrine tumors tested suggests that it may have a role in the unregulated hormone secretion and/or a role in the tumorigenesis of differentiated endocrine tumors. PMID- 8342149 TI - Endotoxin-exposed atria exhibit G protein-based deficits in inotropic regulation. AB - BACKGROUND: Diminished response at the myocardial beta 1-adrenoceptor is established in endotoxemia. The myocardial muscarinic-2 acetylcholine receptor (M2ACHR) has not been investigated in endotoxemia, although it shares a G protein mediated link to adenyl cyclase (AC). This study aimed to assess the contractile responses elicited at the M2ACH and beta 1 receptors, their respective G proteins, and the AC unit in endotoxemia. METHODS: Isometric force and rate of contraction were measured in atria from Sprague-Dawley rats after exposure to 24 hour continuous intravenous infusion of 0.2 mg/kg endotoxin or vehicle. The responses to isoproterenol, acetylcholine, sodium fluoride (NaF), and forskolin were studied. RESULTS: In a comparison of endotoxic versus control atria, diminished force response at the beta 1-adrenoceptor was confirmed (4.98 +/- 1.343 vs 7.26 +/- 1.568 gx10 [gx10 is unit of measure used for force], p = 0.0006, n = 10), and an analogous defect at the M2ACHR was identified (6.66 +/- 0.906 vs 8.16 +/- 1.307 gx10, p = 0.009, n = 10). NaF was able to directly activate Gs and G(i) in a dose-dependent differential manner. Both Gs (5.40 +/- 0.795 vs 7.81 +/- 1.057 gx10, p = 0.0015, n = 6) and G(i) (2.73 +/- 0.528 vs 3.76 +/- 0.332 gx10, p = 0.003) force responses were diminished in endotoxic atria. Stimulus of AC by forskolin yielded similar force increases (3.15 +/- 0.731 vs 3.21 +/- 0.667 gx10, p = 0.89, n = 9). CONCLUSIONS: In this model only contractile responses were altered by endotoxemia. The use of NaF revealed dysfunction distal to agonist receptor interaction and with the data from M2ACHR activation confirmed that this defect is not adrenergic specific. The preserved response at AC localized the site of this myocardial receptor dysfunction to the G proteins. PMID- 8342150 TI - Acute cyclosporine-induced renal vasoconstriction is mediated by endothelin-1. AB - BACKGROUND: Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic side effects. Plasma levels of the vasoconstrictor peptide endothelin-1 are increased after cyclosporine administration, and endothelin-1 has been shown to cause renal vasoconstriction. In this study we used in vivo microscopy to investigate the role of endothelin-1 in cyclosporine-induced vasoconstriction. METHODS: Hydronephrotic kidneys in decerebrate rats were suspended in an environmentally controlled tissue bath with neurovascular supply intact. Interlobular, afferent, and efferent arteriolar diameters and flow were measured by videomicroscopy and Doppler velocimetry. Cyclosporine was added to the tissue bath, and measurements were repeated for 60 minutes. In study groups endogenous endothelin-1 was blocked by infusion of either specific endothelin antiserum or an endothelin-1 receptor antagonist. RESULTS: Cyclosporine caused constriction of the interlobular artery by 20% +/- 2% and a corresponding decrease in blood flow by 66% +/- 4%. The afferent and efferent arterioles constricted to a similar degree. This vasoconstriction was entirely prevented by infusion of either the endothelin antiserum or the receptor antagonist. The antagonist reagents alone had no effect on hemodynamic parameters or renal microvessel diameters. CONCLUSIONS: The acute renal vasoconstriction induced by cyclosporine is mediated by endothelin-1. Endogenous endothelin-1 has little role in maintaining basal vascular tone. PMID- 8342151 TI - 'You will be affected by AIDS, even if you are not infected'. PMID- 8342152 TI - AIDS chairman: epidemic prompts slow response from physicians. PMID- 8342153 TI - Survey reveals physicians are treating inquisitive patients. PMID- 8342154 TI - What is the national commission on AIDS? PMID- 8342155 TI - Firearms are leading cause of injury mortality in Texas ... again. PMID- 8342156 TI - TMA takes decisive steps towards leadership role in health-care reform. PMID- 8342157 TI - Council on socioeconomics studies low-cost electronic claims clearinghouse. PMID- 8342158 TI - The down-to-earth side of space medicine. PMID- 8342159 TI - Council on medical education studies medical examiners, other issues. PMID- 8342160 TI - Chiropractic board may adopt 'worrisome' rules. PMID- 8342161 TI - Navigating the Board of Medical Examiners system. PMID- 8342162 TI - Electroconvulsive therapy. AB - Electroconvulsive therapy (ECT) is a safe, effective, valuable treatment for serious affective disorders (eg, major depression). Sometimes indicated for other, occasionally nonpsychiatric, medical conditions, ECT is a moderately complex procedure for which training is provided routinely during psychiatric residency. Although temporary confusion and amnesia are expected immediately after treatment, no reliable data suggest that permanent memory loss or cognitive deficit is caused by modern ECT. Indeed, because severe depression itself often causes both memory and cognitive deficits, ECT's remarkable therapeutic effectiveness is associated with long-term improvement in cognition, learning ability, and memory for many patients. Controversy over safety and effect on memory is fueled largely by public misinformation. PMID- 8342163 TI - Carotid endarterectomy: a review of surgical practice in a community hospital. AB - That a specified number of vascular surgery procedures must be performed annually to maintain competence and that these procedures require a specialized center have been suggested repeatedly. Recent national guidelines admonish us to check our own experience with carotid surgery. In our 10-year review of 215 operations performed for carotid stenosis and/or ulceration by two surgeons in a relatively small community, the combined major morbidity/mortality rate of 2.8% compares favorably to many other series. Our experience suggests that if done judiciously, gently, and with universal shunting, the operation can be accomplished safely in the community hospital setting. PMID- 8342164 TI - PCRM reiterates stance on cow's milk. PMID- 8342165 TI - Growing RN layoffs. Does Texas mirror the national trend? PMID- 8342166 TI - Legal issues for nurses. Overview of professional liability insurance. PMID- 8342167 TI - THA says: nurses still in demand in Texas. PMID- 8342168 TI - Possible mechanisms of action of cobra snake venom cardiotoxins and bee venom melittin. AB - Cobra snake venom cardiotoxins and bee venom melittin share a number of pharmacological properties in intact tissues including hemolysis, cytolysis, contractures of muscle, membrane depolarization and activation of tissue phospholipase C and, to a far lesser extent, an arachidonic acid-associated phospholipase A2. The toxins have also been demonstrated to open the Ca2+ release channel (ryanodine receptor) and alter the activity of the Ca(2+)+Mg(2+)-ATPase in isolated sarcoplasmic reticulum preparations derived from cardiac or skeletal muscle. However, a relationship of these actions in isolated organelles to contracture induction has not yet been established. The toxins also bind to and, in some cases, alter the function of a number of other proteins in disrupted tissues. The most difficult tasks in understanding the mechanism of action of these toxins have been dissociating the primary from secondary effects and distinguishing between effects that only occur in disrupted tissues and those that occur in intact tissue. The use of cardiotoxin and melittin fractions contaminated with trace ('undetectable') amounts of venom-derived phospholipases A2 has continued to be common practice, despite the problems associated with the synergism between the toxins and enzymes and the availability of methods to overcome this problem. With adequate precautions taken with regard to methodology and interpretation of results, the cobra venom cardiotoxins and bee venom melittin may prove to be useful probes of a number of cell processes, including lipid metabolism and Ca2+ regulation in skeletal and cardiac muscle. PMID- 8342169 TI - Cardiotoxin 1 from cobra (Naja naja atra) venom causes necrosis of skeletal muscle in vivo. AB - Cardiotoxin 1 from cobra (Naja naja atra) venom was tested for its ability to cause necrosis of skeletal muscle cells after i.m. injection into mice. Light and electron microscopic examination of tissue indicated that the toxin caused necrosis of skeletal muscle as early as 30 min after injection. The plasma membranes of affected cells were ruptured in the area of delta lesions, and the myofibrils were condensed into dense clumps alternating with clear areas containing elements of the sarcotubular system and damaged mitochondria. By 24 hr the affected cells appeared as empty 'bags' containing only remnants of myofibrils and swollen mitochondria. To eliminate the possibility that the necrosis was due to contaminating phospholipase A2 (PLA2) activity of the sample, the sample was treated with p-bromophenacyl bromide (p-BPB), a known inhibitor of PLA2 activity. The p-BPB-treated preparation caused myonecrosis in vivo in mice, and the treatment caused a significant decrease in the release of fatty acids and no detectable lysophospholipid in human muscle cell cultures treated in vitro with the preparation, indicating the lack of PLA2 activity. Additionally, purified PLA2 from the same venom failed to cause myonecrosis in vivo at doses equal to or ten times the estimated contaminating concentration. Thus, it is concluded that cardiotoxin 1 from Naja naja atra venom causes necrosis of skeletal muscle cells in vivo upon i.m. injection. PMID- 8342170 TI - Variation in the toxins present in ciguateric narrow-barred Spanish mackerel, Scomberomorus commersoni. AB - Water-soluble and lipid-soluble toxins present in six specimens of Scomberomorus commersoni captured in subtropical Queensland were compared with those detected in a specimen studied earlier. All specimens were from batches that had been involved in human poisonings. All specimens contained significant amounts of potent water-soluble toxins, the most important of which in terms of contribution to the lethal potency of fish flesh was unidentified toxic material which tested positively for alkaloids. All specimens contained lipid-soluble toxins including ciguatoxin-like and scaritoxin-like material, the latter usually predominating. Amounts of water-soluble toxins with lethal potencies ranging from 14.9 MU to 115 MU/100 g of flesh and of lipid-soluble toxins with lethal potencies ranging from 8.8 MU to 39.9 MU/100 g of flesh were found. (A mouse unit, MU, is the minimum amount of toxic material expressed in g required to kill a 20 g mouse within 24 hr following i.p. injection.) The lethal potency of water-soluble toxins per g of fish exceeded that of lipid-soluble toxins per g of fish for five of the seven specimens of S. commersoni now investigated. Based on a lethal dose to humans of 2500 MU all fishes contained lethal amounts of toxic material. The relative amounts of water-soluble and lipid-soluble toxins present in the flesh of a specimen of S. commersoni were altered by different cooking procedures. PMID- 8342171 TI - Different clotting mechanisms of Bothrops jararaca snake venom on human and rabbit plasmas. AB - Bothrops jararaca venom is approximately 3.5 times more effective at coagulating rabbit plasma than human plasma. To investigate this difference B. jararaca venom was treated with several enzymatic inhibitors and the minimum coagulant dose was determined both on plasma anticoagulated with sodium citrate or a mixture of sodium citrate and heparin, and on fibrinogen (both human and rabbit). On human plasma, the thrombin-like component of the venom accounted for c. 60% of the coagulant activity, such activity was negligible on rabbit plasma. The venom had little clotting activity on rabbit fibrinogen. The factor II- and X-activator components could be inhibited by EDTA, EGTA and 2-mercaptoethanol, whereas the thrombin-like activity was inhibited by PMSF. These differences show that (using human plasma) B. jararaca clotting activity is mainly due to the thrombin-like component, whereas the factor II- and X-activator components are more important on rabbit plasma. The delayed action of the thrombin-like enzyme on rabbit fibrinogen may be attributed to the difference between rabbit and human fibrinopeptide A. Thus, the increased coagulant activity on rabbit plasma may be due to a faster rate of activation of factor X, V or II by snake venom enzymes. PMID- 8342172 TI - Biological and biochemical activities of Vipera berus (European viper) venom. AB - Vipera berus is widely distributed throughout the northern part of Europe and Asia. Characterization of several toxic effects of its venom in the mouse, as well as of in vitro enzymatic activities was performed. Vipera berus venom displayed in vitro proteolytic, fibrinolytic, anticoagulant, and phospholipase A2 activities. The i.p. LD50 of the venom for Swiss mice was 0.86 micrograms/g (95% confidence limits 0.71-1.01 microgram/g). Significant local tissue-damaging effects, including edema, hemorrhage and myonecrosis, were observed. The local edema was characterized by rapid onset, reaching a maximum after 0.5-1 hr, and with dose-dependent persistence. The hemorrhagic potency was measured by a skin test, giving a minimum hemorrhagic dose value of 3.2 micrograms. The venom also induced a moderate local myonecrosis, evidenced by histological evaluation of injected tissue (gastrocnemius), and by biochemical parameters (increase of plasma creatine kinase activity, and decrease of muscle residual MTT (3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide)-reducing activity). Characterization of the venom by SDS-polyacrylamide gel electrophoresis revealed 10 (reduced) or 11 (unreduced) main protein bands, which were further analyzed in relation to mol. wt and relative concentration by densitometry. A rabbit antiserum to V. berus venom recognized all main venom bands by immunoblotting. This antiserum cross-reacted to a variable extent with several crotaline venoms, as assessed by enzyme immunoassay. PMID- 8342173 TI - Toxicity of the venom from Nasonia vitripennis (Hymenoptera: Pteromalidae) toward fly hosts, nontarget insects, different developmental stages, and cultured insect cells. AB - A venom preparation from Nasonia vitripennis, a wasp ectoparasitoid of fly pupae, was assayed for lethality in different stages of insects representing ten different orders and in cultured insect cells. In most cases, the motor activity of the injected insects remained completely normal for 1-2 days after the injection and displayed none of the symptoms of paralysis commonly reported for venoms of the Hymenoptera. A natural host, the flesh fly Sarcophaga bullata, was highly sensitive in the pupal stage (LD50 = 5.4 and 5.5 VRE/g for nondiapausing and diapausing pupae, respectively), the stage that is normally parasitized, and larvae and adults were as susceptible to the venom as the pupae. Adults of another fly host, Phaenicia sericata, were nearly as sensitive (LD50 = 6.5 VRE/g), but nonhost adult flies were more tolerant. Among the other orders tested, pupae of several species (Plodia interpunctella, Trichoplusia ni, Tenebrio molitor) were more susceptible to envenomation than larval or adult stages. In fact, the highest sensitivity observed in this study (LD50 = 0.58 VRE/g) was with pupae of the cabbage looper, T. ni, a species that is not a natural host. In contrast, the larvae (LD50 = 7.23 VRE/g) and adults (LD50 = 7.48) of T. ni were far less sensitive. Adults of Nasonia vitripennis were not sensitive to their own venom (LD50 = > 533 VRE/g), although adults of another hymenopteran, Apis mellifera, were suceptible (4.62 VRE/g). Adults of Lymantria dispar, Oncopeltus fasciatus, Aphis nerii, Euborellia annulipes, Diapheromera femorata, Blattella germanica, Periplaneta americana, and Reticulitermes flavipes demonstrated a high tolerance to Nasonia venom. When tested in vitro, the venom caused cultured Lepidoptera (TN-368) and Diptera (NIH SaPe4) cells to round up, swell, and eventually die. The LC50S were 0.0014 and 0.0010 VRE/microliters for TN-368 and SaPe4 cells, respectively. Cytotoxicity was observed within 10 min after exposure to LC99 levels of venom, with 100% cell mortality at 100 min for the NIH SaPe4 cells and 24 hr for TN-368 cells. It is possible that the venom component responsible for in vivo and in vitro activities may be different, but results from the cell culture work suggest that this method offers a promising assay for quickly screening venom samples. The high susceptibility of flies and pupae of other insects to the venom, as well as its novel (nonparalytic) action suggest that it may have considerable potential for development as a biopesticide. PMID- 8342174 TI - Evidence for a fast-exchange conformational process in alpha-bungarotoxin. AB - Anomalous behavior of the post-synaptic protein neurotoxin, alpha-bungarotoxin (alpha-bgt), has been observed during reverse-phase HPLC. Purified samples of this toxin from two distinct sources elute from reverse-phase columns as two separate peaks. The protein species represented by these two peaks are in rapid equilibrium, the relative ratio of which displays a pH dependency with a pKa of approximately 3. This equilibrium does not involve the dimerization or aggregation of the toxin and appears to be relatively unique to alpha bungarotoxin in that similar behavior is not displayed by several other available alpha-neurotoxins. pH-dependent conformational changes have been documented for several alpha-neurotoxins whose crystal structures have been determined (alpha bungarotoxin, alpha-cobratoxin, and erabutoxin b). One or more of these may account for the observed behavior of alpha-bungarotoxin on reverse-phase HPLC. PMID- 8342175 TI - Severity rating scales for ciguatera fish poisoning. AB - Severity of ciguatera fish poisoning is often quite variable. Two symptom check list rating scales were developed for quantifying illness severity and for selectively monitoring response to therapy in patients with chronic toxicity. Content validity was ascertained, and internal consistency reliability was demonstrated by means of the Cronbach alpha correlation coefficient (alpha = 0.9475). It was concluded that these instruments were valid and reliable, and that they conveniently and accurately recorded illness severity and treatment efficacy. They should prove useful in clinical settings and epidemiologic investigations. PMID- 8342176 TI - Structural modifications imparting reduced toxicity in microcystins from Microcystis spp. AB - A cyanobacterial (blue-green algal) bloom containing Microcystis aeruginosa (dominant), M. viridis, and M. wesenbergii, was collected from Homer Lake (Illinois, U.S.A.) in the summer of 1988 and microcystins were isolated. One microcystin of substantially reduced toxicity was isolated, together with ten hepatotoxic microcystins. The compound with reduced toxicity was nonlethal at 1 mg/kg (i.p. mouse) and was determined to have a (C3H7O2) mono-ester of the alpha carboxyl on the Glu unit of microcystin-LR. The other nine microcystins apart from MCLR had approximate LD50S ranging from 97 micrograms/kg to 750 micrograms/kg. PMID- 8342177 TI - The effect of the viper Cerastes cerastes cerastes venom and venom fractions on carbohydrate metabolism. AB - The effect of the viper Cerastes cerastes cerastes venom and venom fractions on carbohydrate metabolism. Toxicon 31, 791-801, 1993.--I.p. injection of a sublethal dose of Cerastes cerastes cerastes venom into white rats induced a marked hypoglycemia after 15 min. This hypoglycemia continued for at least 24 hr. Hypoglycemia was accompanied by a significant increase of liver and muscle glycogen at 15-30 min and 8 hr. Plasma lactate levels were significantly increased for most of the 24 hr test period, and was accompanied by a marked decrease of liver lactate levels. Levels of skeletal muscle lactate increased significantly. Viper venom significantly increased levels of plasma, liver and skeletal muscle pyruvate for most of the 24 hr test period. Cerastes cerastes cerastes venom was fractionated using gel filtration into six fractions. Each of the first four fractions caused a significant hypoglycemic effect at some point of the 6 hr test period, while fraction I also produced a hyperglycemia 30 min after administration. Fraction III, the only fraction to show a continuous hypoglycemic effect during the 6 hr test period, significantly increased plasma insulin levels 30 min after treatment. It is suggested that the hypoglycemia may be due to a direct effect of venom components on plasma insulin levels. PMID- 8342178 TI - Toxin content, phallotoxin and amatoxin composition of Amanita phalloides tissues. AB - The toxin content and composition of Amanita phalloides tissues were determined in three specimens at two carpophore development stages. The carpophore was subdivided into six parts, namely, the cap, gills, ring, stipe, volva and bulb. To our knowledge, this is the first report of such an investigation on the ring and the bulb. Substantial differences in the tissue toxin content were revealed. The ring displayed a very high amount of toxins, whereas the bulb had the lowest toxin content. Compositional differences in relation to the nature of the tissue were also noted. The highest amatoxin content was found in the ring, gills and cap, whereas the bulb and volva were the richest in phallotoxins. Furthermore, variability in the toxin composition was observed. The differences in the distribution of individual toxins in the tissues might be related to the carpophore developmental stage. PMID- 8342179 TI - Is Nai Habarala (Alocasia cucullata) a poisonous plant? AB - Nai Habarala is not documented as a poisonous plant. However, we report two cases of fatal poisoning following ingestion of its fruit. The clinical manifestations have a similarity to cyanogenic glycoside poisoning. PMID- 8342180 TI - Bibliography of toxinology. PMID- 8342181 TI - Public health nurses--a century of caring (1893-1993). PMID- 8342182 TI - Carotid stenosis and perioperative stroke risk in symptomatic and asymptomatic patients undergoing vascular or coronary surgery. AB - BACKGROUND AND PURPOSE: The management of asymptomatic carotid stenosis found before vascular or coronary surgery is unclear from the literature. We aimed to define the relation of carotid stenosis to perioperative stroke in all patients, symptomatic and asymptomatic, and so determine a policy for the management of asymptomatic carotid stenosis in patients requiring major surgery. METHODS: We conducted a prospective clinical and Duplex ultrasound study of 358 consecutive noncarotid major vascular or coronary artery bypass operations, with a moratorium on endarterectomy for asymptomatic carotid stenosis. RESULTS: There were 145 vascular and 213 coronary bypass operations. Ten of the 49 cases with prior symptoms of cerebral ischemia (38 carotid, 11 vertebrobasilar) had symptomatic stenosis of 50% or greater or occlusion, and 3 of these (30%) had ipsilateral perioperative cerebral infarction (95% confidence interval, 6.67% to 65.25%). Two of these occurred ipsilateral to symptomatic carotid occlusions, and 1 occurred ipsilateral to an 80% symptomatic stenosis. One symptomatic patient with bilateral 30% stenosis had a perioperative infarct in the asymptomatic hemisphere. Among the 309 asymptomatic patients, 1 perioperative infarct occurred ipsilateral to carotid stenosis of 30%. In all there were 5 (1.4%) perioperative (within 72 hours) and 2 late (after 18 days) strokes. All strokes were hemisphere infarcts confirmed by computed tomography. There were 53 cases with 50% or greater asymptomatic carotid stenosis or occlusion, including 28 with 80% or greater stenosis or occlusion. None had an ipsilateral perioperative stroke (95% confidence interval, 0% to 6.72%). CONCLUSIONS: We conclude that the risk of perioperative stroke related to symptomatic carotid stenosis may be high, but for asymptomatic carotid stenosis the risk is low and does not justify preoperative prophylactic carotid endarterectomy. PMID- 8342183 TI - Treatment of acute cortical infarct with intravenous glycerol. A double-blind, placebo-controlled randomized trial. AB - BACKGROUND AND PURPOSE: This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infarction in whom intracerebral hemorrhage was rigorously excluded. METHODS: Within 48 hours of symptoms from their first ischemic stroke, 113 hospital inpatients were randomized into the trial, provided that hemorrhage was excluded by computed tomography and informed consent was obtained. Patients were stratified into alert, semicoma, and coma groups using the Glasgow Coma Scale. Treatment was allocated according to a double-blind, randomized protocol; 56 patients received 500 mL of 10% glycerol in saline over 4 hours on 6 consecutive days, and 57 patients received corresponding placebo treatment with saline. Using a variety of objective scoring systems, patient follow-up was up to 6 months. RESULTS: Corresponding measures of outcome in the glycerol and placebo groups were similar. At 6 months, respective mortality rates were 17 of 56 and 16 of 57, and mean +/- SD improvements in scores were 9.98 +/- 14.40 vs 10.51 +/- 12.68 (long term), 1.12 +/- 7.20 vs 1.57 +/- 6.30 (prognostic), -1.94 +/- 5.53 vs -2.06 +/- 5.34 (Glasgow Coma Scale), and 21.72 +/- 23.40 vs 11.94 +/- 18.10 (Barthel Index rating in survivors). Hemolysis (generally subclinical) was the only adverse effect. CONCLUSIONS: There was no clinically or statistically significant difference in outcome between the groups; a trend toward greater functional recovery among survivors was evident after treatment with glycerol. PMID- 8342185 TI - Hyperglycemia in the acute phase of stroke is not caused by stress. AB - BACKGROUND AND PURPOSE: Hyperglycemia in the acute phase of stroke is associated with poor outcome. Whether hyperglycemia in nondiabetic stroke patients is caused by stress is controversial. METHODS: We studied glucose levels and glycosylated hemoglobin in 91 consecutive patients with acute stroke admitted within 24 hours after onset of symptoms. In 27 unselected patients we also measured catecholamines on days 1 and 3 after onset. RESULTS: Hyperglycemia was found in 39 (43%) of the patients, 55% of whom either had diabetes mellitus or latent diabetes; the others had idiopathic hyperglycemia. Norepinephrine levels were associated with the severity of the stroke (P = .005) and with hypertension (P = .03) but not with glucose levels, irrespective of whether or not the patients had diabetes. CONCLUSIONS: We conclude that hyperglycemia in the acute phase of stroke cannot be explained by increased stress. PMID- 8342184 TI - Does low-dose acetylsalicylic acid prevent stroke after carotid surgery? A double blind, placebo-controlled randomized trial. AB - BACKGROUND AND PURPOSE: The aim of this randomized double-blind, placebo controlled trial was to evaluate whether neurological deficits could be prevented with low-dose acetylsalicylic acid (ASA) as an adjunct to carotid endarterectomy. METHODS: A total of 232 patients were randomized to two groups, 75 mg/d ASA starting preoperatively and continued for 6 months (n = 117) or placebo (identical tablets) (n = 115). The patients were followed up regularly for 1 year. RESULTS: The groups were well matched regarding laboratory data and indication for operation. The number of patients with intraoperative or postoperative stroke without complete recovery within 1 week were 0 and 2 at 30 days and 6 months, respectively, in the ASA group, compared with 7 and 11 in the placebo group (P = .01). Including all neurological events within 6 months, this was found in 15 patients in the ASA group compared with 24 in the placebo group (P = .12). Mortality was 0.8% and 3.4% at 30 days and 6 months, respectively, in the ASA group. In the placebo group, the corresponding figures were 4.3% and 6.0%, respectively (P = .12). The intraoperative bleeding did not differ between the groups nor did the number of reoperations due to bleeding or other complications related to pharmacology. CONCLUSIONS: This study indicates that low dose ASA (75 mg/d) reduces the number of postoperative strokes without complete recovery within 1 week. Overall neurological events are insignificantly reduced, as also mortality. The use of low-dose ASA (75 mg) seems safe and effective in reducing cerebrovascular events after carotid endarterectomy. PMID- 8342186 TI - Fibrinogen and the albumin-globulin ratio in recurrent stroke. AB - BACKGROUND AND PURPOSE: In following patients initially recruited for a cross sectional study of blood viscosity in ischemic cerebrovascular disease, it was noted that those having a low albumin-globulin ratio appeared to experience the majority of subsequent vascular events. Accordingly, a prospective study in which subjects were assigned to a high or low albumin-globulin cohort was undertaken to examine the relation between a low albumin-globulin ratio, the presence of clinical risk factors for stroke, and the occurrence of subsequent stroke, myocardial infarction, or vascular death. METHODS: Three groups of subjects were followed for an average of 1.5 +/- 0.8 years to ascertain vascular end points. Group 1 consisted of 126 patients with acute ischemic stroke; group 2 included 109 subjects matched with group 1 for age, medications, and recognized clinical risk factors for stroke; and group 3 was composed of 84 healthy volunteers, matched for age with groups 1 and 2. The median albumin-globulin ratio for group 1 at enrollment, 1.45, was used to dichotomize patients into two cohorts: all subjects with an albumin-globulin ratio of 1.45 or less were assigned to the "low" albumin-globulin cohort; those whose ratio was greater than 1.45 were assigned to the "high" albumin-globulin cohort. The occurrence of vascular end points was verified during subsequent hospitalizations and outpatient clinic visits and by telephone interviews of patients and providers. RESULTS: A total of 51 vascular events occurred, including 39 in group 1, 8 in group 2, and 4 in group 3. Subjects in either group 1 or 2 who were in the low albumin-globulin cohort had at least double the risk for a subsequent vascular event compared with their counterparts in the high albumin-globulin cohort (P < .01 and P < .03, respectively). In comparison with the high albumin-globulin cohort, significantly more patients in the low albumin-globulin cohort in group 1 had a history of prior stroke (P < .03). When groups 1 and 2 were combined, both a low albumin globulin ratio and diabetes had a significant independent association with increased risk for subsequent vascular events in a Cox proportional-hazards model (P < .01 and P < .03, respectively). CONCLUSIONS: The results of this study indicate that significantly increased risk for subsequent vascular events in stroke patients and in subjects with clinical risk factors for stroke is associated with a shift in the concentrations of blood proteins to a prothrombotic environment characterized by lower levels of albumin and an increased concentration of globulins and fibrinogen. PMID- 8342187 TI - Stroke mortality and case-fatality rates in three geographic areas of Finland from 1983 to 1986. AB - BACKGROUND AND PURPOSE: Our aim was to describe the mortality and early case fatality rates of stroke in three geographic areas of Finland during 1983 to 1986 by means of a community-based stroke register and to estimate the accuracy of registration of stroke deaths in the official statistics compared with the FINMONICA stroke register. METHODS: Annual and average mortality and case fatality rates of stroke were derived from data collected in the FINMONICA stroke register during 1983 to 1986. Age-specific and age-standardized rates were calculated for the three areas, and the results were compared with the official mortality statistics and with the case-fatality figures published previously in the literature for Finland and elsewhere. RESULTS: Mortality from stroke in the three FINMONICA areas was between 73 and 90 per 100,000 per year among men aged 25 to 74 years and between 42 and 55 per 100,000 per year among women in the same age group. Average case-fatality was similar in the three areas and globally high: 20% to 27% in men and 24% to 28% in women. Approximately half of the fatal strokes occurred within less than 2 days from the onset of the attack, and a further 25% within the first week. Hemorrhagic strokes accounted for 54% to 81% of all fatal strokes occurring in less than 2 days among men, while among women the corresponding proportions varied in the three areas between 35% and 74%. Of cerebral infarctions, approximately 28% to 37% among men and 19% to 20% among women were fatal within less than 2 days. Although the number of fatal strokes was similar in both the FINMONICA register and official mortality statistics, only 82% to 85% of the stroke cases were common in both registers; a further 13% to 14% of the cases classified as stroke deaths in the FINMONICA register could also be found in the official mortality statistics, but the underlying cause of death was something other than stroke. CONCLUSIONS: The reliability of the Finnish official mortality statistics with regard to stroke deaths is reasonably good in aggregate numbers, but at the individual level considerable discrepancies seem to occur. Mortality from stroke in Finland has not declined further after 1979 and remains high internationally. Early case-fatality of stroke also seems higher in Finland than in most other countries. We believe that both the high incidence of stroke and the severity of the attacks are contributing to mortality and case-fatality rates of stroke in Finland. PMID- 8342188 TI - Regional cerebral blood flow in chronic hypertension. A correlative study. AB - BACKGROUND AND PURPOSE: Cerebral hypoperfusion has occasionally been reported during essential hypertension. We explored regional cerebral blood flow in a large series of neurologically asymptomatic hypertensive patients to determine relations among cerebral blood flow, concomitant main vascular risk factors, and the most common signs of end-organ damage. METHODS: Regional cerebral blood flow was measured by the 133Xe inhalation method in 101 hypertensive patients without clinically apparent central nervous system involvement, including 39 mild to moderate untreated and 62 mild to severe treated patients. RESULTS: Compared with age- and sex-matched normal control subjects, cerebral blood flow was significantly reduced in untreated hypertensive patients (P < .01) and to a lesser extent in treated patients (P = .047). Both regional and global cerebral blood flow reductions were observed in approximately one third of patients in both groups. Analysis of variance failed to show significant correlations between cerebral blood flow and total cholesterol concentration, mean arterial blood pressure, duration of disease, or the presence of retinopathy or left ventricular hypertrophy. In the treated group, the quality of control of hypertension significantly influenced both global cerebral blood flow (P = .007) and cerebrovascular resistance (P < .0001). CONCLUSIONS: Focal or diffuse cerebral hypoperfusion is present even in neurologically asymptomatic hypertensive patients, especially when untreated; good control of blood pressure may preserve cerebral perfusion and reduce cerebrovascular resistance. Regional cerebral blood flow examination represents a relatively simple and low-cost technique to explore the perfusional condition of the brain, one of the main target organs of hypertensive disease. PMID- 8342189 TI - Cerebral blood flow velocity and systemic vascular resistance after acute reduction of low-density lipoprotein in familial hypercholesterolemia. AB - BACKGROUND AND PURPOSE: Low-density lipoprotein apheresis is currently used for the treatment of familial hypercholesterolemia, an inherited disorder of metabolism associated with premature development of cardiovascular disease. We wanted to evaluate cerebral blood flow velocity, cardiac output, and systemic vascular resistance in patients with familial hypercholesterolemia before and after low-density lipoprotein apheresis. METHODS: Ten patients (age range, 14 to 46 years; 4 males, 6 females) with familial hypercholesterolemia (8 homozygotes, 2 heterozygotes) and 10 healthy control subjects of comparable age and sex distribution participated in the study. Low-density lipoprotein apheresis by dextran sulfate was performed in 8 patients (7 homozygotes, 1 heterozygote). Six patients (4 homozygotes, 2 heterozygotes) underwent a procedure of extracorporeal erythrocyte filtration with the same extracorporeal volume as for low-density lipoprotein apheresis, but with the exclusion of the passage of plasma through the dextran sulfate column. Cerebral blood flow velocity (transcranial Doppler), cardiac output, and systemic vascular resistance (electric bioimpedance cardiography) were determined by noninvasive techniques before and 1 day and 7 days after low-density lipoprotein apheresis or extracorporeal erythrocyte filtration. Plasma and blood viscosities were measured at the same time. RESULTS: Before apheresis, mean and diastolic cerebral flow velocities were abnormally low in hypercholesterolemic patients (P < .01 and P < .02 vs healthy control subjects, respectively). After apheresis, low-density lipoprotein cholesterol was lowered by 40% to 60% from baseline, and cerebral blood flow velocities (mean, systolic, and diastolic velocities) were increased (P < .01). Cardiac output, systemic vascular resistance, and viscosity values were not significantly modified. Extracorporeal erythrocyte filtration (without passage of plasma through the dextran sulfate column) did not modify serum lipids, hemodynamic parameters, or viscosity values. CONCLUSIONS: Low-density lipoprotein apheresis produces potentially useful hemodynamic effects. They are not adequately explained by changes in blood viscosity alone and might reflect a restoration of endothelium-mediated vasodilation, which is inhibited by high concentrations of low-density lipoprotein. PMID- 8342190 TI - Brain stem infarction and diaschisis. A SPECT cerebral perfusion study. AB - BACKGROUND AND PURPOSE: We studied six patients suffering from pure, unilateral brain stem infarction to explore the association of remote cerebral and cerebellar blood flow changes with damage at different sites of this region of the brain. METHODS: We used single-photon emission computed tomography and [123I]iodoamphetamine to measure regional differences in tracer uptake. Qualitative image analysis and calculated asymmetry indexes were correlated to the location of the infarcted area on magnetic resonance imaging and to the patients' clinical findings. RESULTS: Significant perfusion asymmetries were noted in the two patients with infarction in the upper pons but not in those with lesions below this level. They comprised a contralateral cerebellar and ipsilateral supratentorial hypoactivity that was most marked in the frontoparietal cortex. There was no clear relation between the patterns of cerebral or cerebellar tracer uptake and specific neurological findings. CONCLUSIONS: Remote perfusion changes after pure brain stem infarction may be seen both infratentorially and supratentorially and depend on the lesion site rather than on the neurological deficit. In this context, our study confirmed damage to the corticopontocerebellar pathways as the key event in the genesis of a crossed cerebellar diaschisis. The exact mechanisms causing ipsilateral cerebral hemispheric diaschisis await further clarification. PMID- 8342191 TI - Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine and its redistribution in ischemic cerebrovascular disease. AB - BACKGROUND AND PURPOSE: The relation between the redistribution phenomenon and regional cerebral blood flow and its clinical significance were investigated in stroke patients. METHODS: Single-photon emission computed tomography studies using N-isopropyl-p-[123I]iodoamphetamine were performed on 16 patients (26 to 77 years old) with chronic infarction and 10 age-matched normal control subjects. Regional cerebral blood flow was quantitatively measured by a microsphere model, and the redistribution on delayed images was analyzed in ischemic lesions. RESULTS: Supratentorial mean cerebral blood flow and the ratio of gray matter to white matter in normal subjects were 52.7 +/- 5.0 mL/100 g per minute and 2.34, respectively. Low-activity areas of ischemic lesions on early images were classified into two abnormal zones, an infarct area and a peri-infarct area. These regions were characterized by regional blood flow averaging 9 to 20 mL/100 g per minute and 22 to 41 mL/100 g per minute, respectively. Redistribution, which was minimally present in the infarct area, was markedly enhanced in the peri-infarct area. After bypass surgery, we observed a significant increase of blood flow (+22%) in the peri-infarct area. CONCLUSIONS: The data indicate that the redistribution phenomenon depends on the maintenance of a minimal blood flow that would sustain cellular function and that this phenomenon is useful to evaluate bypass surgery in patients with chronic infarction. PMID- 8342192 TI - The Frenchay Activities Index. Assessment of functional status in stroke patients. AB - BACKGROUND AND PURPOSE: Assessment of functional status in stroke patients is of major importance in both clinical practice and outcome studies. The Frenchay Activities Index has been developed specifically for measuring disability and handicap in stroke patients. The purpose of the study was to evaluate the metric properties of this instrument and to obtain normal values in a group of unselected elderly subjects. METHODS: The Frenchay Activities Index was tested in a group of stroke patients and a group of unselected subjects aged 65 or older. The functional status of the stroke patients was measured 26 weeks after stroke. Their prestroke status was registered retrospectively. Reliability and validity of the instrument were assessed. RESULTS: The mean scores in the prestroke, poststroke, and control group demonstrated differences in functional status. The reliability of unweighted scores (range of Cronbach's alpha-coefficients, 0.78 to 0.87) was sufficient. The construct validity was supported by meaningful correlations between the Frenchay Activities Index and scores on the Barthel Index and Sickness Impact Profile. Principal-components analysis indicated that the Frenchay Activities Index showed two traits: instrumental disability and some aspects of handicap. The reliability of the instrument could be improved by deleting two items and by creating two subscale scores: domestic and outdoors activities. CONCLUSIONS: The Frenchay Activities Index is a useful stroke specific instrument to assess functional status. Completion of the questionnaire is easy and takes only a few minutes. Currently, the instrument is suitable for use in patient care and cross-sectional, descriptive studies. PMID- 8342193 TI - A comparison of five stroke scales with measures of disability, handicap, and quality of life. AB - BACKGROUND AND PURPOSE: Recently much debate has arisen on the appropriateness of assessing stroke outcomes with stroke impairment scales. Our purpose was to study the relationship between long-term impairments and functional outcomes in terms of disability, handicap, and quality of life. METHODS: We studied 87 patients who had a stroke 6 months earlier. Impairments were scored on five stroke scales: the Orgogozo Scale, the National Institutes of Health scale, the Canadian Neurological Scale, the Mathew scale, and the Scandinavian Stroke Scale. Disability was assessed with the Barthel Index, handicap with the Rankin scale, and quality of life with the Sickness Impact Profile. The linear relationship between stroke scales and functional scales was assessed with correlation coefficients. We used regression analyses to explain functional health. RESULTS: The stroke scales were highly related to one another (range, r = -.85 to .92). The correlation between stroke scales and functional scales was < .70 and decreased from Barthel (mean r2 = 47.5%) to Rankin (mean r2 = 36.5%) to Sickness Impact Profile (mean r2 = 33%). Stroke scales were rather poorly correlated with patients' psychosocial conditions (mean r2 = 11.5%). Functional health status was mainly related to leg power and orientation. The standardized stroke scale weights of the explanatory items were lower than their standardized regression weights. CONCLUSIONS: Stroke scales only partly explain functional health. The impact of impairments on functional outcomes seems to be underestimated by the stroke scale weights. The correlation patterns give empirical support to the hierarchical structure of the International Classification of Impairments, Disabilities and Handicaps. PMID- 8342194 TI - Factors influencing return to work after stroke in Japan. AB - BACKGROUND AND PURPOSE: Few studies have identified factors that predict return to work after stroke in Japan. Our aim in this study was to determine the predictors of return to work after stroke in Japan. METHODS: We performed a retrospective cohort study on the association between patients' characteristics at admission and return to work in 230 first-stroke patients, adjusting for potential confounding factors. The patients were all aged younger than 65 years and were working, students, or housewives at the time of their stroke. Return to work was evaluated by a follow-up questionnaire. Data were analyzed using forward logistic regression analysis to compute odds ratios of return to work. RESULTS: The adjusted odds ratios (and 95% confidence intervals) for patients with normal muscle strength vs severe muscle weakness, without apraxia vs with apraxia, and with white-collar vs blue-collar occupation were 4.50 (1.04 to 19.42), 4.87 (1.28 to 18.54), and 3.33 (1.34 to 8.30), respectively. CONCLUSIONS: Significant predictors of return to work after stroke were no muscle weakness, absence of apraxia, and white-collar occupation. PMID- 8342195 TI - The effects of long-term rehabilitation therapy on poststroke hemiplegic patients. AB - BACKGROUND AND PURPOSE: Rehabilitation therapy is believed to be useful during the first few months after stroke when recovery usually takes place. However, evidence exists that this may not be the rule for all stroke victims. Therefore, we investigated, in a selected group of poststroke patients, the profile of recovery in response to long-term rehabilitation therapy. METHODS: Fifty-one hemiplegic subjects unable to walk 3 months after stroke were enrolled in this study. Patients underwent consecutive periods of rehabilitation up to 2 years after the cerebrovascular accident. Autonomy in daily living activities and the degree of neurological compromission were periodically assessed with the Barthel Index and a neurological scale designed for hemiplegic subjects. The main features of the patients were also evaluated as a possible predictor of outcome. RESULTS: In a consistent percentage of the patients, significant gains in gait and daily living abilities were observed during the first year and, in individual cases, during the second year after stroke. At the end of the study, 74% of the patients regained their capacity to walk without assistance, and up to 79% had a Barthel Index score above 70. Sphincter function, level of neurological impairments, and capacity in daily living activities are significantly related to the outcome of the patients as a whole but were not useful to anticipate the outcome of each patient. CONCLUSIONS: These results suggest that disabled poststroke subjects may attain significative functional improvements in response to prolonged restorative therapy. However, the possibility of predicting the outcome of individual patients appears the major problem to solve in order to assign to long-term rehabilitation programs only patients who will benefit from the therapy. PMID- 8342196 TI - Rate of successful recording of blood flow signals in the middle cerebral artery using transcranial Doppler sonography. AB - BACKGROUND AND PURPOSE: To assess the usefulness of transcranial Doppler sonography, we investigated the rate of blood flow signal recording failure in the middle cerebral artery in Japanese subjects. Furthermore, we studied the effect of increased emitted power on the rate of successful recording in some of the patients in whom recording failure had been detected at the standard transducer power of 100 mW/cm2. METHODS: To evaluate the rate of successful recording, we measured blood flow signals in 597 patients (age range, 16 to 89 years) for screening of cerebrovascular disease by using a 2-MHz range-gated, pulsed-wave Doppler instrument at the standard transducer power. In 18 elderly patients with recording failure at the standard power, we assessed the effect of increased emitted power of 400 mW/cm2 on flow signal recording. RESULTS: Blood flow signals were recorded in 920 (77.1%) of the 1194 middle cerebral arteries of the 597 patients studied. The rate of successful recording of bilateral middle cerebral artery flow signals (70.9%; 423 of 597 patients) decreased with age, especially in females (17.0% in women aged 70 years or older). In 12 of 18 elderly patients with recording failure at the standard power, blood flow signals could be detected at the increased emitted power of 400 mW/cm2. CONCLUSIONS: The rate of successful recording of blood flow signals in Japanese subjects decreases with advancing age, especially in females. Increasing the emitted power markedly improves the successful recording rate. PMID- 8342197 TI - Color Doppler imaging of orbital arteries for detection of carotid occlusive disease. AB - BACKGROUND AND PURPOSE: Distal to a hemodynamically significant stenosis, the Doppler effect becomes dampened. Thus, measuring the flow profile in the ophthalmic artery and the central retinal artery with color Doppler imaging may provide hemodynamic information about the carotid circulation. METHODS: To validate the flow profile measurement with color Doppler imaging in the ophthalmic and central retinal arteries and to determine the sensitivity and specificity of this examination in the detection of hemodynamically significant carotid stenosis, we compared color Doppler imaging examinations with ocular pneumoplethysmography and ophthalmodynamometry examinations in 66 patients with atherothrombotic ischemic cerebrovascular disease. The degree of carotid stenosis in these patients was determined by a duplex scan with color Doppler imaging, and 57 patients underwent angiography to verify the stenosis. RESULTS: The flow velocities (systolic peak velocity and end-diastolic velocity) and pulsatility indices (A/B ratio and resistance index) in the ophthalmic and central retinal arteries decreased as the degree of carotid stenosis increased. There is a statistically significant difference in the mean of systolic peak velocity and the mean of end-diastolic velocity of the ophthalmic and central retinal arteries among groups with various degrees of carotid stenosis (P < .02). Using the flow velocities of the ophthalmic and central retinal arteries to diagnose carotid stenosis (> or = 75% stenosis and occlusion), 8 cm/s for systolic peak velocity in the central retinal artery and 29 cm/s for systolic peak velocity plus flow direction reversal in the ophthalmic artery gave the maximum accuracy (sensitivities, 84% and 85.7% and specificities, 89.6% and 81.7%, respectively). The systolic peak velocity in the central retinal artery varied directly with the systolic pressure of the ophthalmic and central retinal arteries. CONCLUSIONS: The flow velocity and pulsatility in orbital arteries examined by color Doppler imaging provide further hemodynamic information; this test can be used to complement current sonographic examination of carotid disease. PMID- 8342198 TI - Use of neuroanesthesia adjuncts (hyperventilation and mannitol administration) improves neurological outcome after thoracic aortic cross-clamping in dogs. AB - BACKGROUND AND PURPOSE: Using a canine model of thoracic aortic cross-clamping, we compared the incidence and severity of paraplegia with and without standard neuroanesthesia adjuncts (mannitol administration and deliberate hyperventilation). Better outcome was predicted for animals treated with mannitol and hyperventilation. METHODS: Nineteen dogs (mean +/- SD weight, 21 +/- 3 kg) were anesthetized with methohexital to an isoelectric electroencephalogram. Animals were randomized to group C (control; n = 9) or group M (mannitol administration and deliberate hyperventilation; n = 10). In group C, animals were maintained normocapnic (PaCO2, 38 to 42 mm Hg). In group M, animals were hyperventilated to a PaCO2 of 28 to 32 mm Hg and received mannitol 2 g.kg-1 during surgical preparation, then 1 g.kg-1.h-1 by continuous infusion. The thoracic aorta was cross-clamped for 30 minutes. Systemic hemodynamics, cerebrospinal fluid pressure, and arterial blood gases were measured at (1) baseline, (2) 2 minutes after cross-clamp, (3) 20 minutes after cross-clamp, (4) 5 minutes after cross-clamp release, and (5) 30 minutes after resuscitation. No attempt was made to control the hemodynamic consequences of cross-clamping in either group. With release of the cross-clamp, PaCO2 was not controlled in group C; in group M the minute ventilation was further increased to maintain PaCO2 constant. At precisely 24 hours after cross-clamp the animals were assessed for incidence and severity of paraplegia, using the Tarlov score, by an observer unaware of the experimental protocol. The animals were killed, and the entire spinal cord was removed for histological assessment. Multiple sections of the lumbar spinal cord were processed and stained with hematoxylin and eosin. RESULTS: With application of the cross-clamp, cerebrospinal fluid pressure and central venous pressure increased significantly in both groups. However, in group M the maximal mean cerebrospinal fluid pressure never exceeded baseline values in group C. With cross-clamp release, spinal cord perfusion pressure (distal mean aortic pressure minus mean cerebrospinal fluid pressure) was significantly greater in group M (86 +/- 23 vs 65 +/- 17 mm Hg; P = .0017 between groups). Acid base balance was better maintained in group M. The incidence and severity of paraplegia were significantly lower in group M (P = .043; Mann-Whitney rank-sums test, two-tailed). In this group 10 of 10 animals could walk and 4 of 10 had complete recovery. In group C 4 of 9 animals were paraplegic. There was a strong negative correlation between the Tarlov score and the ratio of dead to total anterior spinal cord neurons in the lumbar region as assessed by light microscopy (P = .0004; Spearman's rank test). CONCLUSIONS: We conclude that a protocol using standard neuroanesthesia adjuncts (mannitol administration and deliberate hyperventilation) is associated with improved neurological outcome after thoracic aortic cross-clamping of 30 minutes' duration in dogs anesthetized with methohexital. PMID- 8342199 TI - The effects of hypertension on cerebral atherosclerosis in the cynomolgus monkey. AB - BACKGROUND AND PURPOSE: There is substantial clinical, pathological, and experimental evidence that hypertension aggravates atherosclerosis of the extracranial vessels. The present study assesses the effects of hypertension on the development of cerebral atherosclerosis in nonhuman primates fed an atherogenic diet. METHODS: The extent and severity of cerebral atherosclerosis were evaluated morphologically, morphometrically, and biochemically in atherosclerotic monkeys with and without hypertension. Atherosclerosis was induced by feeding a hypercholesterolemic diet for 12 months; hypertension was produced by surgical coarctation of the thoracic aorta. RESULTS: At autopsy, gross atherosclerotic lesions of the major cerebral arteries were observed in 15 of 16 atherosclerotic monkeys with hypertension compared with 5 of 16 atherosclerotic animals without hypertension. In the hypertensive-atherosclerotic group, 38.5% of the vessels examined showed gross involvement compared with only 3.4% of the vessels involved in the atherosclerotic group (P < .001). The lesions in the atherosclerotic group were generally mild, whereas those in the hypertensive-atherosclerotic group were severe and resulted in significant luminal narrowing and occlusion of vessels (P < .001). The small branches of the cerebral arteries also showed severe disease with luminal obstruction in the hypertensive-atherosclerotic group. The extent and severity of cerebral atherosclerosis were significantly related to the severity of the hypertension (P < .05). CONCLUSIONS: Hypertension is an important factor in cerebral atherosclerosis because of its accelerating effect on the disease. Nonhuman primate models may be useful in clarifying the role of hypertension and atherosclerosis in cerebral vascular disease. PMID- 8342200 TI - Postischemic (1 hour) hypothermia significantly reduces ischemic cell damage in rats subjected to 2 hours of middle cerebral artery occlusion. AB - BACKGROUND AND PURPOSE: We investigated the effect of hypothermia induced 1 hour after transient (2-hour) middle cerebral artery occlusion on the extent of ischemic cell damage in the rat. METHODS: Middle cerebral artery occlusion was induced extracranially by insertion of a nylon filament into the right internal carotid artery. Two groups of rats were investigated: (1) rats (n = 10) subjected to normothermic (37 degrees C) ischemia and normothermic reperfusion; and (2) rats (n = 10) subjected to normothermic ischemia and 1 hour of normothermic reperfusion followed by 3 hours of hypothermia (30 degrees C). All rats were killed 1 week after the experiment, and brain sections were stained with hematoxylin and eosin for evaluation of ischemic cell damage. RESULTS: Infarct volume in normothermic rats involved 20.9 +/- 4.6% of the hemisphere, whereas hypothermic rats exhibited a significantly smaller (P < .001) infarct volume of 11.1 +/- 2.7%. The numbers of surviving (or structurally intact) neurons within large sections of the cortex and striatum were significantly greater for hypothermic compared with normothermic rats (P < .01). CONCLUSIONS: Our data suggest that postischemic induction of hypothermia significantly reduces ischemic cell damage after 2 hours of middle cerebral artery occlusion in the rat, and that an interval of time of at least 1 hour after ischemia exists in which hypothermic intervention is effective in either salvaging or postponing irreversible neuronal injury. PMID- 8342201 TI - Bilirubin levels in subarachnoid clot and effects on canine arterial smooth muscle cells. AB - BACKGROUND AND PURPOSE: Previous studies have suggested that bilirubin is a potential contributor to cerebral vasospasm. The purpose of this investigation was to determine whether bilirubin accrues in subarachnoid clot, whether its vasoconstrictive effect could involve a direct action on arterial smooth muscle cells, and, if so, whether bilirubin affects their Ca2+ uptake. METHODS: Subarachnoid clots were analyzed for bilirubin using high-performance liquid chromatography. The length and 45Ca2+ uptake of vascular smooth muscle cells enzymatically dissociated from canine carotid arteries were measured before and after exposure to bilirubin solution. Additional experiments were conducted on cultured smooth muscle cells from canine basilar artery and on ATP-depleted cardiac myocytes. RESULTS: Mean +/- SE bilirubin concentration in experimental clot was 263 +/- 35.7 mumol/L. Vascular smooth muscle cells exposed to bilirubin showed progressive shortening (P < .01) and an increased uptake of 45Ca2+ (P < .001). Contraction was prevented by Ca(2+)-free media but not by verapamil. Experiments with heart myocytes showed that bilirubin caused an increased uptake of 45Ca2+ but not of [14C]sucrose. CONCLUSIONS: The results indicate that bilirubin accrues in subarachnoid clot, that it exerts a direct constrictive effect on arterial smooth muscle cells, and that this effect is associated with an increased uptake of Ca2+. Studies on heart myocytes suggest that the Ca2+ uptake induced by bilirubin could be due to a selective increase in membrane permeability to Ca2+. PMID- 8342202 TI - Transcranial Doppler detection of circulating cerebral emboli. A review. AB - BACKGROUND: The identification of gaseous emboli using Doppler ultrasound was described as early as the 1960s. Recently it has been demonstrated that this method can also detect solid emboli such as thrombi and platelet aggregates. This may make this technology useful in a large number of patients with, or at risk of, embolic stroke. SUMMARY OF REVIEW: Emboli appear as short-duration, high intensity signals in the Doppler spectrum. The intensity of the Doppler signal from an artery containing an embolus depends on the density difference between the embolic material and blood. This difference is greatest for gaseous emboli, which are therefore the most easy to detect. Gaseous emboli have been demonstrated during deep-sea diving, and their presence correlates with the occurrence of decompression sickness. Similar signals have been detected during cardiopulmonary bypass. A relation has been demonstrated between the number of emboli detected by transcranial Doppler and a decline in neuropsychological function after cardiopulmonary bypass. Solid emboli such as thrombi and platelet aggregates result in less intense signals than air emboli. Their detection, using Doppler ultrasound, has recently been described in patients with prosthetic heart valves, atrial fibrillation, and carotid artery disease. It may also help in the detection and localization of embolic sources in patients with stroke. Studies in in vitro and in vivo models demonstrate that this technique provides information on the size and type of emboli. Larger emboli produce signals of greater intensity and duration. Practical patient monitoring will require automatic emboli detectors incorporated into the Doppler machine; such programs are being developed. CONCLUSIONS: Detection of solid emboli using Doppler techniques offers an exciting new diagnostic tool. It has been demonstrated that the technique can detect solid emboli. The prognostic significance of such emboli remains to be determined. It is hoped that the technique will allow detection of patients at high risk of embolic stroke in whom appropriate prophylactic treatment can then be instituted. PMID- 8342203 TI - Aspirin: optimal dose in stroke prevention. PMID- 8342205 TI - Stroke triggered by an asthma attack. PMID- 8342204 TI - Increased 99mTc-HMPAO uptake in ischemic stroke. PMID- 8342206 TI - Chorea in a child with Churg-Strauss syndrome. PMID- 8342207 TI - Cerebrovascular events in cardiac catheterization. PMID- 8342208 TI - Magnetic resonance imaging in basilar artery dissection. PMID- 8342209 TI - An evaluation of postvention following adolescent suicide. AB - This study sought to evaluate postvention provided to two schools following student suicides. A risk index for suicidal behavior among exposed adolescents was devised. The index clearly differentiated high (n = 272) and low (n = 534) scorers on a range of outcome variables. While two-thirds of students attending postvention counselling had two or more putative risk factors for suicidal behavior, a further 231 uncounselled students had similar risk scores. Counselled students (n = 63) did not differ from matched controls (n = 63) at 8-month follow up on a range of outcome variables. Measures to improve future postvention are discussed. PMID- 8342210 TI - The relationship of drug use to suicide ideation and attempts among African American, Hispanic, and white non-Hispanic male adolescents. AB - This study presents self-report cross-sectional and longitudinal data on associations between drug use, suicide ideation, and attempts in a multiethnic sample of seventh- and eighth-grade male adolescents attending school in the greater Miami, Florida, area. African Americans had the highest prevalence of 6 month ideation (20.5%), and Haitians had the highest attempts (11.4%). For the total sample, tranquilizers had the highest odds ratio for ideation (3.4), and PCP for attempts (6.2). Psychoactive drug-use was consistently related to attempts among Hispanics, white non-Hispanics, and African Americans. Acculturation strains interacted with cocaine and crack to predict suicide attempts among Hispanic respondents. PMID- 8342211 TI - The impact of a suicide prevention program for adolescents on suicidal tendencies, hopelessness, ego identity, and coping. AB - Three-hundred ninety-three adolescents from six schools participated in a study aimed at examining the effectiveness of an experiential suicide prevention program with regard to suicidal tendencies, hopelessness, ego identity, and coping ability. The subjects were randomly divided into experimental (n = 215) and control (n = 178) groups. The experimental groups took part in seven weekly 2 hour meetings. The program was based on the notion that a gradual, controlled confrontation and exploration of inner experiences and life difficulties related to suicidal behavior accompanied by an emphasis on coping strategies can immunize against self-destructive feelings. In this pretest-posttest design, the students completed questionnaires of suicidal tendencies, hopelessness, ego identity, and coping ability before and after the program. The statistical analyses showed that the experimental groups were superior to the controls, with at least some of the dependent measures pointing out the effectiveness of the program. PMID- 8342212 TI - Double jeopardy: suicide rates in forensic hospitals. AB - While a number of studies have described high and increasing rates of completed suicide among psychiatric patients, the suicide risk of forensic hospital patients is virtually unknown. This paper reports on the suicides that have taken place in the country's oldest continually operating institution housing persons formerly labeled "criminally insane," the Bridgewater State Hospital. The results show considerable variation in the suicide rate by historical period, with suicide prior to 1968 a considerably more infrequent event. By contrast, the post '68 rate of 232 per 100,000 is comparable to data reported in a series of studies of psychiatric suicides, and significantly higher than that found in U.S. studies of correctional populations. These differences are discussed. The results strongly suggest that forensic hospital populations have suicide rates broadly comparable to other psychiatric populations. PMID- 8342213 TI - Hopelessness, depression, suicidal ideation, and clinical diagnosis of depression. AB - The relevance of a clinical diagnosis of depression for explaining the discrepant relationships of hopelessness and depression with suicidal ideation was studied. The Beck Depression Inventory (BDI), Hopelessness Scale (BHS), and the Scale for Suicide Ideation (SSI) were administered to 1,306 (72.8%) patients with at least one DSM-III-R mood disorder and 488 (27.3%) patients without any mood disorders. A multiple regression analysis was conducted, and hopelessness was 1.3 times more important than depression was for explaining suicidal ideation. The interactions of the BDI and BHS with diagnostic group were not significant. PMID- 8342214 TI - Control group studies of suicide survivors: a review and critique. AB - Empirical studies of suicide survivors with designs that include control groups are reviewed. Investigations are discussed individually with respect to those in which participating survivors are friends or a combination of many different relationships to the deceased, parents of the deceased child, and spouses. Following the review is a brief discussion of the commonalities of the findings and the most frequent methodological difficulties. Concluding comments suggest methodological improvements as well as issues and groups for which additional investigations are needed. PMID- 8342215 TI - Inpatient treatment planning. PMID- 8342216 TI - Characteristics of completed suicides: implications of differences among methods. AB - Approximately 30% of suicides in New York City are the result of jumping from a height. After describing jumping suicides and jumping sites, we used polychotomous logistic regression to compare the characteristics of suicides by jumping to those of individuals committing suicide by hanging, ingestion, or shooting. Method used was significantly associated with sociodemographics, occupation, and mental health status, even after adjustment for individual access to the means of committing suicide. Our finding of an independent association between personal characteristics and method used provides strong evidence for the hypothesis that controlling access to an agent of suicide can influence overall suicide rates, at least in the short term. Study results support the introduction of preventive programs to control access to commonly employed agents of suicide. PMID- 8342217 TI - Head trauma. Perioperative nursing implications. AB - 1. The highest mortality rate in the adult trauma patient population is among those presenting with acute head trauma and associated multiple trauma. 2. Motor vehicle crashes are the leading cause of head trauma, with alcohol being a primary associated factor. The other major mechanisms of head trauma are falls and assaults. 3. Secondary brain injury is a result of brain swelling and intracranial hemorrhage causing hypoxia and ischemia of the brain tissue. 4. The goals of surgical intervention are to evacuate intracranial hematoma and prevent increases in intracranial pressure. PMID- 8342218 TI - Orthopedic trauma: pelvic fracture. AB - 1. The incidence of pelvic fractures has greatly increased; automobile and motorcycle crashes, pedestrian accidents, and falls from great height are the most common causes. Pelvic fractures caused by high-energy trauma often result in significant morbidity and mortality with mortality rates variously reported at 10% to 50%, dependent upon fracture classification and associated injuries. Mortality occurs from associated trauma to viscera, abdominal organs, and abdominal vessels, and from early complications of hemorrhage. 2. The difficulty in management of patients with pelvic fractures is determining whether fractures are stable or unstable. Single breaks with no displacement in the pelvic ring, which includes injuries to the ischium, ilium, pubis, and sacrum, are stable fractures and account for one third of all pelvic fractures. 3. Increasingly widespread use of surgical stabilization internally via rigid fixation of pelvic fractures has helped reduce the morbidity and mortality related to these fractures. Other benefits that have resulted include shortened hospitalization, decreased complications, and earlier mobility. PMID- 8342219 TI - Admission surgery: the patient with abdominal and thoracic trauma. AB - 1. Epidemiology may affect admission. It is essential to know what types of trauma patients are typically admitted, at what time of day, and on which day of the week. Within trauma systems, one of the major determinants of patient survival is the adequacy of surgical personnel and equipment resources. 2. Assessment of the abdominal and thoracic trauma patient is an active process, requiring constant curious attention. Due to the time-critical nature of these injuries, effective communication is paramount. There may be little or no documentation, and minimal verbal report, consisting of mechanism of injury and vital signs. A stable patient may rapidly deteriorate. 3. Injury severity and location are key in patients' mortality and morbidity. Outcomes for vascular injury surgeries depend on time lag, differences in surgeons' experience, associated injury, site of wounds, type of arterial lesions, and infection. PMID- 8342220 TI - Pediatric trauma: preparation and management. AB - 1. Trauma causes more than 50% of the deaths in children. The leading cause of pediatric injury is motor vehicle accidents involving children as passengers, pedestrians, or bicycle riders. 2. Trauma is always unexpected; therefore, the most vital aspect of any trauma system is that the system itself never be caught unprepared. Anticipation and preparation are the best first-line defenses against traumatic injury. 3. Because of a child's smaller size, vital organs are in close proximity to one another; multiple organ injuries are common. 4. The team who responds to a pediatric trauma should include nurses and physicians trained in principles of pediatric resuscitation. PMID- 8342221 TI - Microsurgical instrument handling systems. A new approach to instrument budget control. AB - 1. Large portion of a hospital's supply budget is allocated for repair and replacement of surgical instruments. Microsurgical instrumentation can account for 18% or more of a total OR budget. 2. Managing the surgical instrument repair and replacement budgets with greater emphasis on accountability can help demonstrate effective cost containment. Cost savings may be experienced through appropriate use of surgical instrument management systems for handling, sterilization, and storage of microsurgical instruments. 3. Many facilities are implementing quality control programs to minimize replacement and repair costs, to ensure surgical instrument integrity, and to extend the life of their investment. Education, management information systems, improved communication, and appropriate use of instrument handling systems are some components of budget accountability in the operating room. PMID- 8342222 TI - A perioperative nursing challenge: trauma in the OR. PMID- 8342224 TI - Business and nursing: interdependence? PMID- 8342223 TI - Preparing a nursing department for downshifting. AB - 1. Downshifting is a movement away from intense job attention and a focus toward the family. Many individuals in all parts of America are shifting their focus away from materialism and financial prosperity, and toward a simpler lifestyle and homelier values. This increasing focus on family--rather than career--can also be seen in nursing. 2. Motivation to downshift because of decreasing interest in career is less likely when the employee is a nurse. However, rising emphasis on the hazards of latchkey children and the need for quality parenting have increased nurses' concerns about the effect of being out of the home for extended periods. 3. With today's nursing shortage, personnel policies must be responsive to the priorities of the prospective job applicant. To be desirable, an employer must appear responsive to personal needs. The national trend to make positions more compatible with home responsibilities must be incorporated in personnel strategies if nurses are to remain in nursing positions and be satisfied. PMID- 8342225 TI - Safe practices key to preventing fires in the OR. PMID- 8342226 TI - When the manager shares work responsibility. AB - Delegation can be an effective tool for the OR manager in completing work activities in a more timely manner. A manager with skill in delegation can make the work environment a more positive and enjoyable place in which to work, while at the same time increasing productivity. PMID- 8342227 TI - OR resuscitation for trauma patients. AB - 1. The results of multiple studies have shown evidence that immediate access to the operating room has significantly contributed to improved outcome in several categories of trauma patients. 2. "Walk through" table top exercises were held in the OR suite to identify problems. These mock resuscitations were particularly helpful in solving logistical and equipment problems. 3. Prehospital care providers were given classes regarding triage criteria and operating room logistics. 4. Continuing education for OR and trauma nurses included videotape review and critique of ORR, trauma-specific inservice programs presented by the trauma coordinators and physicians, and attendance at weekly videotape review and trauma conference presented by the Division of Trauma. Easy recognition of individual team members, an important issue, required the use of name badges. PMID- 8342228 TI - Is white cell reduction cost-effective? PMID- 8342229 TI - Column agglutination technology: the antiglobulin test. AB - A new system for typing and screening blood, based on the sieving effect of glass bead microparticles, has been developed. The test is performed in a microcolumn in which the red cell agglutinates are trapped in the glass bead matrix during centrifugation, and unagglutinated cells form a pellet at the bottom of the column. Anti-human globulin reagents were incorporated in the diluent and the new test system, column agglutination technology, was compared to conventional tube tests and low-ionic-strength method. Sera and plasmas (228 samples) were screened for red cell antibodies with two anti-human globulin reagents: one containing only anti-IgG and the other containing both anti-IgG and anti-C3b, -C3d. After initial testing, there was 94-percent agreement between column agglutination technology and tube tests, and after repeat testing, there was 97-percent agreement. The column agglutination technology anti-human globulin test eliminates the need to wash red cells, which decreases the overall test time. The test is easy to perform, and the results are more objective than those with tube and microplate methods. PMID- 8342230 TI - Platelet crossmatches of single-donor platelet concentrates using a latex agglutination assay. AB - A latex agglutination assay was evaluated for the purpose of identifying compatible platelet donors for alloimmunized recipients. Assay reagents were prepared by adsorbing detergent-solubilized, donor-specific platelets to polystyrene latex beads. Semiquantitative results for up to 30 donors can be completed in less than 1 hour. These reagents retained their immunoreactivity for at least 3.5 months. A retrospective study has established the assay's upper limit of compatibility. The prospective study evaluated transfusions to a group of multiply transfused patients. Part I evaluated 143 crossmatched, single-donor platelet transfusions given to 50 patients. In 96 percent of the cases, a positive crossmatch was associated with an unsuccessful transfusion outcome; in 84 percent of the transfusions, a negative crossmatch predicted a satisfactory platelet increment. The overall predictability, sensitivity, and specificity were 87, 62, and 99 percent, respectively. Part II evaluated 105 transfusions given to the 43 patients (of 50) in whom no incidence of fever, sepsis, or bleeding could be documented. A positive crossmatch was 96-percent efficient in predicting an unsuccessful transfusion, whereas a negative crossmatch was associated with an adequate platelet increment following 89 percent of the transfusions. The overall predictability was 91 percent, the sensitivity was 72 percent, and the specificity was 99 percent. Within-run and between-run variations were 6.3 and 6.2 percent, respectively. These results demonstrate that detergent-solubilized platelet antigens, immobilized on latex particles, can be used in a cost effective crossmatching procedure. PMID- 8342231 TI - Differential effect of cryopreservation on natural killer cell and lymphokine activated killer cell activities. AB - The use of lymphokine-activated killer (LAK) cell therapy in delayed treatment requires the use of cryopreserved effector cells. The purpose of this study was to determine the optimal cryopreservation protocol for the maintenance of cytotoxic activity in mononuclear cells (MNCs). MNCs were cryopreserved with dimethyl sulfoxide or 1,2-propanediol before and after 3 days of culture with recombinant interleukin 2. The effects of cryopreservation on cell recovery, LAK cell and natural killer (NK) cell cytotoxic activities, and surface antigen markers were studied. Recovery of nonactivated MNCs was higher with 1,2 propanediol than with dimethyl sulfoxide (p < 0.05). Cytotoxic activities, measured with a 51Cr release assay, significantly decreased after thawing, on both activated cells (76.3%; range, 35.8-92.2%) and fresh cells (54.6%; range, 17.5-75.4%). A 6-day kinetic test was used to compare the cytotoxic activity of cryopreserved and fresh cells. The results showed different patterns for NK cells (cryopreserved cells had lower levels of activity than fresh cells) and LAK cells (cryopreserved cells had higher levels of activity than fresh cells). Phenotype changes of effector cells in culture, with and without cryopreservation, were monitored by flow cytometry using monoclonal antibodies. These results were compared with changes in the cytotoxicity of cells with and without cryopreservation. After thawing, there was a decrease in MNCs expressing CD14 and CD56. Recovery of the CD56 marker correlates with increased cytotoxic activity. Despite some loss of NK cell activity, it is concluded that MNCs may be successfully cryopreserved before their use in immunotherapeutic treatment. PMID- 8342232 TI - Analysis of the expression of neutrophil-specific antigen NB1: characterization of neutrophils that react with but are not agglutinated by anti-NB1. AB - The neutrophil-specific NB antigen system has been serologically characterized with human alloantisera. Two alleles, NB1 and NB2, have been described. NB1 is expressed on a subpopulation of peripheral blood neutrophils in 97 percent of healthy donors. Human alloantibodies have been used to identify the 58- to 64-kDa glycoprotein (GP) on which NB1 is located. NB1 can usually be detected by both a granulocyte immunofluorescence (GIF) assay and a granulocyte agglutination (GA) assay, but neutrophils from some donors have been found to react with anti-NB1 in GIF but not in GA assays. To determine if the latter neutrophils express NB1 and the corresponding 58- to 64-kDa GP, these neutrophils were probed with rabbit and human sera specific for NB1. First, the proportion of neutrophils that express NB1 was quantitated. Neutrophils from donors that typed as NB1-positive in both GA and GIF assays were analyzed by flow cytometry with antisera to NB1. Human and rabbit anti-NB1 reacted with 71 +/- 17 percent and 70 +/- 17 percent of neutrophils, respectively. There was no difference in the expression of NB1 in NB1-homozygous and NB1-heterozygous individuals. In contrast, significantly fewer neutrophils from four donors that typed as NB1-positive in GIF assay but not GA assay reacted with human (27 +/- 12%; p < 0.001) and rabbit (26 +/- 12%; p < 0.001) anti-NB1. When neutrophils from these same four donors were probed with rabbit and human anti-NB1 by immunoblotting and immunoprecipitation, the 58- to 64-kDa GP was identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342233 TI - Effect of storage time on clinical efficacy of single-donor platelet units. AB - Decrements in platelet function and recovery are known to accumulate during the 5 day storage period, and the clinical response to platelets transfused after several days' storage has been suggested by some researchers to be less than that seen with platelets stored for shorter periods. The clinical response to single donor platelet (SDP) units (as measured by corrected count increments [CCIs] and intertransfusion intervals) was investigated in autologous bone marrow transplant patients. Twenty-seven consecutive autologous bone marrow transplant patients with a variety of hematologic and solid organ malignancies were evaluated for posttransfusion CCIs after 419 SDP transfusions of units stored for 1 to 5 days. Patients were not excluded from the study because of clinical condition, such as fever or sepsis. The mean 15-minute posttransfusion CCI for SDP units stored for only 1 day (11,006 +/- 5,157) was no different than that for units stored for 5 days (10,225 +/- 4,481; p > 0.05); 24-hour posttransfusion CCIs were also not different if the SDP unit had been stored for 1 day or 5 days (6229 +/- 4489 vs. 4786 +/- 2759; p > 0.05) or for any intermediate period. Nor were intertransfusion intervals affected by storage time. While platelets may exhibit a progressive lesion during the 5-day storage period, these changes do not result in a decreased clinical response. PMID- 8342234 TI - Cost-effectiveness of white cell-reduction filters in treatment of adult acute myelogenous leukemia. AB - The objective of this study was to compare the cost and cost-effectiveness of three transfusion strategies in the treatment of acute myelogenous leukemia: 1) the use of unfiltered pooled platelets until alloimmunization developed and of crossmatch-compatible single-donor platelets thereafter; 2) the use of filtered blood components until alloimmunization occurred and of crossmatch-compatible single-donor platelets thereafter; and 3) the use of single-donor platelets from the beginning. The data sources were English language articles on transfusion medicine in acute leukemia and the management of acute leukemia and review of the transfusion experience at the H. Lee Moffitt Cancer Center. The method was decision analysis with a software program for cost-effectiveness, sensitivity analysis, threshold evaluation, and Monte Carlo sensitivity analysis. In the basic models, the total costs of the first, second, and third strategies are, respectively, $12,557.14, $11,406.17, and $13,016.16 without bone marrow transplant and $14,002.72, $12,281.89, and $13,727.48 with bone marrow transplant. The threshold between the first and second strategies in regard to risk of refractoriness to filtered blood components and pooled platelets was 0.30 and 0.27, respectively, without bone marrow transplant and 0.28 and 0.40 with bone marrow transplant. According to a Monte Carlo sensitivity analysis of 500 samples, the second strategy is more cost-effective than the first in 76 percent of cases. It is concluded that the use of filtered blood components is unlikely to increase the cost of treatment. PMID- 8342235 TI - Changes in intention to donate blood under a hypothetical condition of reduced confidentiality. AB - Lawsuits related to transfusion-associated human immunodeficiency virus infections have increasingly resulted in requests for the release of confidential information about volunteer blood donors. Concern that loss of confidentiality might change blood donor behavior led to a survey of donors at collection sites within an American Red Cross Blood Services Region. Of the 361 respondents, 50.3 percent (181) indicated reduced intent to provide accurate medical and personal history information under conditions of reduced confidentiality. Ten percent (34) indicated that they were not sure whether they would or would not donate blood in the future under this condition. The results indicate that the possibility of release of donors' medical and personal information may have a negative effect on the safety and adequacy of the nation's volunteer blood supply. PMID- 8342236 TI - Strategies to recruit plateletpheresis donors from a registry of HLA-typed, unrelated, bone marrow donors. AB - Rising demand for single-donor platelet components--from random donors, to maintain platelet inventories, or from HLA-compatible donors, to support alloimmune platelet-refractory patients--necessitated increasing the size of a community plateletpheresis donor registry. This study compares two strategies for recruiting whole-blood donors into a plateletpheresis program. The whole-blood donors who were asked to participate in this study had recently joined an unrelated bone marrow donor registry and had been HLA-typed as part of that process. An in-person recruitment strategy, which was time-intensive for the apheresis donor coordinator, served as the standard. A by-mail strategy involved the mailing of recruitment materials to marrow-donor registry participants. Marrow-donor registry participants were approached about apheresis participation after they had indicated an interest in the plateletpheresis program by returning a tear-off section of an informational brochure that was sent to them along with their marrow-donor registry materials. A total of 852 marrow-donor registry participants were randomly assigned to one of two recruitment strategies, and the recruitment rates were the same (46%) for both methods. In addition, levels of apheresis participation and attrition rates of donors recruited by either strategy were comparable. Thus, the simple strategy of mailing information about a plateletpheresis program is a very cost-effective method of recruiting donors. PMID- 8342237 TI - The effect of sterilization on transforming growth factor beta isolated from demineralized human bone. AB - Growth factors have been identified as the primary cause of osteoinduction in bone healing. Transforming growth factor beta (TGF-beta) has been shown to promote bone formation and is present in bone in high quantities. The aims of the present study were to isolate TGF-beta from human bone, demonstrate its biologic activity, and analyze the effects of conventional sterilization techniques on activity. Bone, obtained from femoral heads of five patients (mean age, 70 years) was ground, demineralized, and freeze-dried, and samples from each patient were divided into three groups: no treatment, sterilization with 1.60 to 1.94 Mrad of 60Co irradiation, and sterilization with ethylene oxide (ETO). Carrier-free recombinant TGF-beta control was also treated and was totally inactivated by ETO but not by irradiation (p < 0.01). TGF-beta activity in demineralized bone was not significantly diminished (p > 0.1) by either sterilization procedure, and substantial amounts of active TGF-beta were recovered in all bone samples: 1.04 +/- 0.77 ng per mg of protein in irradiated samples, 0.67 +/- 0.26 ng per mg in ETO-treated samples, and 1.04 +/- 0.33 in untreated samples, respectively (mean +/- SD). Although a recent report demonstrated that the osteoinductive activity of bone morphogenetic protein in bone powder is diminished considerably by ETO and by 2.5 Mrad of irradiation sterilization of bone powder, these data demonstrate that TGF-beta activity, with its osteoinductive properties, was not destroyed in more coarsely ground, demineralized bone by ETO or by lower doses of irradiation. These findings support the use of human bone allografts in clinical instances involving impaired bone formation. PMID- 8342239 TI - Hemolytic anemia associated with injection of fluorescein. AB - A 49-year-old woman presented with a hemoglobin level of 9.5 g per dL (95 g/L), reticulocyte count of 6.7 percent (0.067), and hemoglobinuria. The next day, the hemoglobin had dropped to 5.8 g per dL (58 g/L), and total bilirubin was 8.8 mg per dL (150 mumol/L). The serum reacted 2+ with all red cells (RBCs). The direct antiglobulin test (DAT) was 3+ with anti-IgG and 1+ with anti-C3, but eluates prepared by two different methods did not react with untreated RBCs. The eluate reacted 2+ with amoxicillin-coated RBCs; amoxicillin had been listed in the patient's record as a previous medication. The patient denied recent ingestion of amoxicillin. Further investigation documented the injection of a dye, fluorescein sodium (AK-FLUOR-25%), for a ophthalmologic fluorescein angiographic study 2 days before admission. RBCs coated with AK-FLUOR reacted with the eluate. Controls consisting of normal serum, an eluate prepared from DAT-negative RBCs, and a serum known to contain anti-penicillin did not react with AK-FLUOR-coated RBCs. Nine days later, the DAT was negative and the serum did not react with untreated RBCs. In the presence of AK-FLUOR (1-in-125) or amoxicillin (1 mg/mL), the serum reacted 2+ in the antiglobulin test. Antibodies to AK-FLUOR and amoxicillin appeared to react by two mechanisms, which is similar to results in recent reports of other drugs associated with hemolytic anemia. AK-FLUOR has not previously been reported to be associated with hemolytic anemia. PMID- 8342238 TI - Antibodies to hydrocortisone in reagent red cells causing positive antibody screening tests. AB - When a patient's serum contains a temperature-independent antibody reacting with all antibody screening and antibody identification panel cells but with few or no units of blood used for crossmatching, one should suspect an antibody against a constituent of the suspension medium of the reagent blood cells. This observation is confirmed by negative reactions with a) washed reagent cells or b) another manufacturer's cells that do not contain the same additives. Two patients are described with antibodies to hydrocortisone that are present in one manufacturer's antibody screening cells and identification panels. The hydrocortisone was added by the manufacturer to prevent hemolysis of the reagent red cells. The patient's antibodies were IgM, complement independent, and nonneutralizable by prior incubation with hydrocortisone. The addition of hydrocortisone to other manufacturers' reagents converted previously negative reactions to the same level of positivity as was seen with the reagent from the index manufacturer. Antibodies to reagent constituents can cause delays in finding compatible blood. It is suggested that manufacturers delete irrelevant additives or those of questionable necessity from their reagents. PMID- 8342240 TI - The specificity of enzyme immunoassays for antibodies to human immunodeficiency virus: impact on record and donor management. PMID- 8342241 TI - Guidelines for counseling human T-lymphotropic virus type I (HTLV-I)- and HTLV type II-infected persons. PMID- 8342242 TI - Ursodeoxycholic acid--new drug for liver diseases. PMID- 8342243 TI - Hydatid jaundice--an overview. PMID- 8342244 TI - Outcome of patients with pre-existing hepatitis B virus infection following renal transplant. AB - Twenty four patients who were HBsAg positive prior to renal transplantation were studied with respect to their hepatic and renal outcome. The kidneys in all patients were obtained from living related donors. The standard immunosuppressive therapy consisted of azathioprine and prednisolone. Post-renal transplant follow up varied from 32-86 months (mean 55 +/- 9). Renal functions, liver functions, HBsAg and HBsAb status was closely monitored during follow-up. One patient developed acute hepatitis four months after transplantation; this resolved in 10 weeks. Four patients showed transient elevations of liver enzymes. The results of liver biopsy in 16 cases revealed, normal histology (8), virus in hepatocytes (5), and acute hepatitis (3). None of the patients had evidence of chronic liver disease. Two patients died due to chronic rejection/chronic renal failure and two patients died due to septicaemia. Five living patients have mild to moderate chronic rejection. It was concluded that pre-existing HBsAg carrier state in transplant patients had no deteriorating effect on the liver. The mortality was related to chronic rejection and septicaemia. PMID- 8342245 TI - The anatomy of an epidemic (the final report on an epidemic of multidrug resistant enteric fever in eastern India). AB - Two hundred and forty two patients of enteric fever were treated at Command Hospital (EC) Calcutta, during the period 1989-90. The mean age of the patients was 28.4 (range 2-60) years and 119 (49.2%) of them were males. Fever (100%), headache (55%), diarrhoea (25.2%), intestinal bleeding (2.9%) and icterus (3.7%) were the main presenting features. Blood cultures were positive in 216 (%) patients. A majority of the isolates were found to be resistant to all four commonly used drugs for enteric fever i.e. chloramphenicol, ampicillin, cotrimoxazole and furazolidone. The commonest phage type found in the resistant strains was 51 (biotype-1). Two plasmids of 14 and 120 kd size were detected in the resistant strains but not in the sensitive strains. Clinical response to gentamicin was not satisfactory in spite of all strains showing in vitro sensitivity. Ciprofloxacin proved to be a safe and effective drug for the treatment of multidrug resistant enteric fever. PMID- 8342246 TI - Pancreatic abscess: is there a role for conservative therapy? AB - Pancreatic abscess is a serious complication of acute pancreatitis and non operative management has been reported to carry a mortality of nearly 100%. We present five patients with pancreatic abscess, who were successfully treated with antibiotics alone. All 5 patients had acute pancreatitis followed by prolonged fever and development of an abdominal mass. The diagnosis was confirmed in each of them by a contrast enhanced CT scan and an ultrasound guided aspiration of pus from the pancreatic mass. The choice of antibiotics was decided by the culture reports in two cases and by Gram's staining in the remaining three patients. We attribute the success of antibiotic therapy in our patients to early diagnosis by CT scan and guided aspiration as well as the absence of any unfavourable risk factors. This study suggests that a select group of patients with pancreatic abscess may be managed conservatively with antibiotics. PMID- 8342247 TI - Amoebic liver abscess. AB - Sonography is a major advance in the diagnosis of ALA. Identification of amoebic antigen in the pus is a specific immunodiagnostic test. Medical therapy with a single drug (metronidazole) is adequate in most instances. Routine needle aspiration or surgical drainage are not indicated. The abscess cavity may take up to 18 months for resolution and demonstration of such a lesion does not warrant repeated therapy unless clinical evidence of recurrence is present. Recurrences are rare. Clinical and laboratory evidences of poor prognosis are being identified, and may guide the treatment modality to be selected. PMID- 8342248 TI - Long common channel syndrome as etiology of choledochal cysts and pancreatitis- two instructive cases. AB - The aetiology of choledochal cysts is controversial. The authors report two cases of Type I C and Type IV B choledochal cysts; both showing axial dilatation of the common bile duct and common hepatic ducts, single fusiform (Type IC) and multiple cysts of extrahepatic ducts only (Type IVB). Both had anomalous junction of the pancreaticobiliary ductal system as delineated on ERCP leading to the formation of a long common channel. Both these female patients presented in the third decade of life with 7-8 years history of repeated episodes of right upper abdominal and epigastric pain suggestive of pancreatitis. Similar pain was precipitated in both patients following ERCP with raised serum amylase. Hepatico enterostomy gave lasting relief in both these patients. PMID- 8342249 TI - Can DNA aneuploidy study make surveillance colonoscopy more cost effective. PMID- 8342250 TI - Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism. AB - Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (iRTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had lower plasma standard bicarbonate after fasting (P < 0.01) and lower urinary excretion of titratable acid (P < 0.05) and citrate (P < 0.01) compared with NUA patients and NC, and higher urinary excretion of ammonia (P < 0.05) compared with NC (P < 0.05). Hypercalciuria was found in 6 of 10 patients with iRTA compared with 3 of 10 with NUA, and 0 of 10 NC. The citrate/calcium ratio in urine was significantly reduced in iRTA compared with the value in NUA (P < 0.01), and in NUA compared with NC (P < 0.05). Biochemical markers of bone formation (serum osteocalcin) and bone resorption (urinary hydroxyproline) were significantly increased in iRTA compared with NUA and NC (P < 0.01), indicating increased bone turnover in stone formers with iRTA. Stone formers with iRTA thus presented with disturbed calcium, bone and citrate metabolism--the same metabolic abnormalities which characterize classic type 1 RTA. Mild non-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA. PMID- 8342251 TI - Calcium phosphate: an important crystal phase in patients with recurrent calcium stone formation? AB - Stone and urine composition were analysed in 75 men and 40 women with recurrent calcium oxalate stone disease (group R) and in 48 men and 19 women who had formed only one calcium-oxalate-containing stone (group S). Patients who had developed stones with a large fraction of calcium phosphate were significantly more frequent in group R than in group S. There was furthermore a higher excretion of calcium and higher calcium oxalate supersaturation levels in patients with stones containing more than 25% calcium phosphate. It was concluded from these observations that the calcium phosphate content of renal stones might be a useful factor in predicting the future course of the disease. PMID- 8342252 TI - Solubility, inhibited growth and dissolution kinetics of calcium oxalate crystals in solutions, containing hippuric acid. AB - An analysis of crystal growth and dissolution of slightly soluble salts in physiological solutions in the presence of complexing ions was carried out, simulating conditions typical in human urine. It was found that hippuric acid, a normal physiological constituent of urine, acts at increased concentrations as a dissolving agent with respect to calcium oxalate (CaOx) and CaOx calculi. The kinetics of dissolution of crystalline CaOx calculi in physiological solutions containing hippuric acid at different concentrations were studied, using the change in the Archimedean weight of samples immersed in the solution. Analysis of the experimental results enabled the determination of the increased solubility of CaOx in the presence of hippuric acid and the quantitative characterization of this substance as a new and promising agent for dissolving CaOx calculi in human urine. The possible effect of hippuric acid as a natural regulator of CaOx supersaturation and crystallization in human and mammalian urine is also discussed. PMID- 8342253 TI - Heparin sulfate in the stone matrix and its inhibitory effect on calcium oxalate crystallization. AB - The nature of the soluble stone matrix and its possible role in urinary stone formation was studied. For this purpose we performed two-dimensional cellulose acetate membrane electrophoresis of the glycosaminoglycans (GAGs) which were contained in the soluble stone matrix, substances adsorbed onto calcium oxalate crystals in vitro (crystal surface binding substances, CSBS) and urinary macromolecules (UMMs). The main GAG in the soluble stone matrix and CSBS was found to be heparan sulfate, whereas the UMMs contained various GAGs usually seen in urine. An inhibition assay showed the soluble stone matrix to have the strongest inhibitory activity among these macromolecular substances when inhibitory activity was expressed in terms of uronic acid concentration. It is suggested that the main GAG in the soluble stone matrix consists of heparan sulfate, which has a strong inhibitory activity on calcium oxalate crystal growth and aggregation and constitutes part of the CSBS. PMID- 8342255 TI - Urodynamic evaluation and electrical and pharmacologic neurostimulation. The rat model. AB - We introduce a rat model that allows simultaneous or independent recording of bladder and sphincteric activity. Via a polyethylene tube inserted into the bladder dome, bladder pressure is measured in response to constant intravesical saline perfusion. The electrical activity of the intra-abdominal urethra (a well defined striated muscular tube which, in the rat, constitutes the external urethral sphincter) is recorded simultaneously with an electromyography needle electrode. Thus, precise statements can be made about detrusor/sphincter interrelationships. Changes in urodynamic parameters with the anesthetics urethane, methoxyflurane (Metofane), and thiobutabarbital sodium (Inactin) were investigated. High-frequency oscillations in intraluminal bladder pressure could be demonstrated during micturition cycles only in rats anesthetized with urethane or Metofane. As this high-frequency activity is generated by the striated muscle of the intra-abdominal urethra, the external sphincter of the rat is the force behind urine expulsion. The anesthetic Inactin combined with a low intravesical perfusion rate attenuated spontaneous bladder and sphincteric activity and abolished micturition cycles. This rat model can provide accurate and reproducible measurements of urodynamic changes in response to electrical stimulation of the pelvic and pudendal nerves and pharmacologic stimulation with neuropeptides at the lumbosacral spinal cord level. We recommend using this model with urethane or Metofane for physiologic studies of micturition and with Inactin for meticulous neuropharmacologic and electrostimulatory evaluation of urodynamic parameters. PMID- 8342254 TI - Assessment of high-energy phosphorus compounds in the rat kidney by in situ 31P nuclear magnetic resonance spectroscopy: effect of ischemia and furosemide. AB - 31P nuclear magnetic resonance (NMR) spectroscopy of the in situ rat kidney was performed by a surface coil method, and the effects of ischemia and furosemide infusion were assessed. 31P NMR spectra of the kidney subjected to 30 min of ischemia returned completely to the pre-ischemic level after 60 min of reperfusion. But the 31P NMR spectra after 60 min of ischemia did not recover, even after 120 min of reperfusion. Levels of beta-ATP and inorganic phosphate (Pi) decreased and the chemical shift of Pi increased after intravenous infusion of furosemide. This increase in chemical shift might signal an alkalotic change in intracellular pH. Furosemide infusion prior to ischemia is thought to protect the kidney from injury induced by 60 min of warm ischemia. The chemical shift of Pi returned to the pre-ischemic level earlier than beta-ATP and Pi. In conclusion, according to the findings of 31P NMR spectroscopy, furosemide infusion prior to ischemia may be effective in protecting the kidney against ischemic injury. But the change in Pi peak and the causes of the dissociation of Pi and beta-ATP should be examined further. PMID- 8342256 TI - Inhibitory effects on in vitro cell growth of human urothelial tumor cell lines under the combined administration of hematopoietic growth factors and clinically relevant antineoplastic agents. AB - In five of eight human transitional carcinoma cell (TCC) lines a proliferative response has been reported during exposure to interleukin-3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF). To elucidate possible growth-modulating effects of these factors combined with clinically relevant antineoplastic agents, cells of the human TCC lines EJ28 and T24 were exposed to methotrexate (MTX), vinblastine (VBL), doxorubicin (DXR) and cisplating (CDDP) with and without single or continuous exposure to IL-3, GM-CSF and G-CSF at concentrations of 1-100 ng/ml. Compared with cells exposed only to chemotherapy, significant inhibitory effects occurred as a result of continuous exposure to IL-3 or GM-CSF at the highest activities with CDDP and MTX in the T24 and EJ28 lines; continuous G-CSF administration (100 ng/ml) in combination with MTX led to significant growth inhibition in the EJ28 line. In contrast, no significant growth modulation was found on combined administration of DXR or VBL with any one of the three colony stimulating factors tested. PMID- 8342257 TI - A bioresorbable urethral stent. An experimental study. AB - The aim of the present study was to examine the suitability of biodegradable polymers as materials for a urethral stent. A new urethral stent made of biodegradable self-reinforced poly-L-lactide (SR-PLLA) was implanted in 16 male rabbits after urethrotomy. Seven stents of stainless steel served as controls. The dimensions of the two types of stents were identical: length 15 mm, diameter 8.2 mm. The mechanical construction was a helical spiral. The SR-PLLA spiral was sustained with three microspirals, and the whole device was coated with DL lactide to achieve an active initial tissue reaction and better tissue penetration. The SR-PLLA stent showed more favourable implantation properties than the steel one. Within 6 months all PLLA stents had implanted, and the tissue reaction around the stent material was minimal. The helical spiral of stainless steel induced a remarkable inflammatory reaction due to poor implantation properties. We suggest that biodegradable SR-PLLA is a promising material for a urethral stent to prevent re-stenosis of urethral strictures. PMID- 8342258 TI - Isolation and in vitro translation of messenger RNA encoding allergens of the cat flea, Ctenocephalides felis. AB - Polyadenylated [poly(A)+] mRNA was isolated from the cat flea, Ctenocephalides felis by oligothymidylic acid-cellulose spin column chromatography and translated in vitro using a cell-free rabbit reticulocyte system. The relative incorporation of 35S-methionine into trichloroacetic acid-precipitable translation products obtained using poly (A+) mRNA was 48.5-fold over control translations performed without added mRNA. SDS-PAGE analysis of the translation products in combination with autoradiography showed that many proteins with apparent molecular weights in the range 14-90 K were synthesized. Immunoprecipitation studies performed using flea-allergic dog sera showed that several of the synthesized proteins corresponded with flea allergens. The allergenicity of the lysates was also confirmed by skin testing. PMID- 8342259 TI - Immune cell distribution in the small intestine of the pig: immunohistological evidence for an organized compartmentalization in the lamina propria. AB - Using monoclonal antibodies in immunohistochemistry, the distribution of the cells with the following surface antigens was studied in samples of proximal and distal small intestine of five 6-month-old pigs: CD2, CD4 (helper/inducer T cells), CD8 (suppressor/cytotoxic T cells), accessory cell marker (monocyte/granulocyte), MHC Class II (DRw), and interleukin 2 (IL-2) receptor. CD2+ cells were found in high numbers in both the epithelium and the lamina propria. More cells were demonstrated in villis than in crypts (proportion approximately 4:1). At least two subpopulations of intraepithelial lymphocytes were identified: apically in the epithelium there were CD2+CD4-CD8- (double negative) cells, whereas cells expressing CD8 marker were concentrated around the basement membrane. CD4+ cells were localized in the lamina propria towards the villus core. Accessory cells were distributed in crypts and the villus base and more cells were found in ileum than in duodenum. In contrast, MHC Class II+ cells were located predominantly in villi, just underneath the basement membrane, forming a sheath of cells between the CD8+ and the CD4+ cells. Cells expressing IL-2 receptor were sparse but widely distributed in both the lamina propria and the epithelium. This organized cell distribution may be related to the physiology of the mucosal immune system in the gut. PMID- 8342260 TI - Purification and characterization of IgG1 and IgG2 from buffalo (Bubalus bubalis) serum and colostrum. AB - Buffalo IgG1 and IgG2 were purified from serum and colostrum using salt precipitation, dialysis, gel filtration and ion-exchange chromatography. Their purity was monitored by immunodiffusion and immunoelectrophoresis using anti heavy chain specific sera and SDS-PAGE. Selective binding of IgG2 to protein-A was used to remove IgG2 from IgG1 preparations. The IgG1 and IgG2 had a molecular mass (Mr) of 162.0 and 161.5 kD, respectively and were found to consist of heavy (H) and light (L) chains. The H and L chains had Mr of 58 and 24 kD, respectively. Reduction-alkylation followed by gel filtration was used for the isolation of H and L chains. While intact H chains were obtained, the L chains appeared to be cleaved into 14 kD molecules and smaller fragments. The mean hexoses content of the serum IgG1 and IgG2 was 1.81 +/- 0.02% and 0.70 +/- 0.02%, respectively. The corresponding values for colostral IgG1 and IgG2 were 1.76 +/- 0.01% and 0.78 +/- 0.08%. Both the IgG subclasses activated homologous complement. These results suggest that buffalo and cattle IgG subclasses have many common characteristics and minor differences. PMID- 8342261 TI - Quantification of antibody secreting cells to Yersinia ruckeri by ELISPOT assay after in vivo and in vitro immunization of rainbow trout (Oncorhynchus mykiss). AB - The ELISPOT assay was applied for the quantification of total and specific antibody secreting cells (ASC) in spleen after in vitro immunization and in head kidney and blood after in vivo immunization of rainbow trout with Yersivax vaccine. The highest number of total and specific anti-Yersinia ruckeri ASC was obtained on Day 21 after in vivo immunization and on Day 10 after in vitro immunization of spleen. PMID- 8342262 TI - Treatment of B-cell lymphoma using peptides. A novel concept. AB - Combination chemotherapy remains the major current treatment of non-Hodgkin's lymphoma. B-cell lymphoma often has tumor-specific surface immunoglobulins called idiotypes. Clinical trials using murine monoclonal anti-idiotype antibodies as a targeting approach have shown some success. I describe a novel concept of using idiotype-specific peptides as an alternative targeting approach for the treatment of B-cell lymphoma. In brief, octapeptides that bind to the surface idiotype of the B-cell lymphoma are isolated from a large synthetic peptide library (10(6) to 10(7) peptides). Once the sequence of a tumor-specific octapeptide ligand is defined, large quantities can be synthesized and conjugated with a radionuclide (such as iodine 131). This should permit highly specific destruction of lymphoma cells that bind the labeled peptide. The theoretic advantages of this approach over the previous use of anti-idiotype antibodies are addressed. PMID- 8342263 TI - Human T-lymphotropic virus type I seroprevalence among Japanese Americans. AB - The epidemiology of human T-lymphotropic virus type I (HTLV-I) infection is not well defined in Japanese Americans. This impairs using approaches that could reduce viral transmission and monitor carriers for the disease. Using enzyme linked immunosorbent assay and p21e recombinant Western blot testing, HTLV-I antibody was measured in unlinked samples from Japanese-American patients at 4 physicians' offices in San Francisco, California. Of 442 patients, 4 (0.9%; 95% confidence interval 0.25%, 2.3%) were confirmed seropositive, all with an HTLV-I rather than an HTLV-II pattern on Western blot. Seroprevalence was highest among the issei or immigrant generation (3/230 or 1.3%) compared with the second generation nisei (1/191 or 0.5%) or third-generation sansei (0 of 17). Prevalence did not differ by age or sex, although the number of positive subjects in each subgroup was small. Of 88 patients with familial origins in endemic areas of southern Japan, none were seropositive. In this sample of Japanese Americans, HTLV-I seroprevalence was lower than in residents of endemic southern Japan but higher than among American blood donors. The prevalence was most similar to that in nonendemic areas of Japan. The public health implications of HTLV-I infection among Japanese Americans are discussed. PMID- 8342264 TI - Effect of preoperative suggestion on postoperative gastrointestinal motility. AB - Autonomic behavior is subject to direct suggestion. We found that patients undergoing major operations benefit more from instruction than from information and reassurance. We compared the return of intestinal function after intra abdominal operations in 2 groups of patients: the suggestion group received specific instructions for the early return of gastrointestinal motility, and the control group received an equal-length interview offering reassurance and nonspecific instructions. The suggestion group had a significantly shorter average time to the return of intestinal motility, 2.6 versus 4.1 days. Time to discharge was 6.5 versus 8.1 days. Covariates including duration of operation, amount of intraoperative bowel manipulation, and amount of postoperative narcotics were also examined using the statistical model analysis of covariance. An average savings of $1,200 per patient resulted from this simple 5-minute intervention. In summary, the use of specific physiologically active suggestions given preoperatively in a beleivable manner can reduce the morbidity associated with an intra-abdominal operation by reducing the duration of ileus. PMID- 8342266 TI - 34-year-old woman with hypotension, respiratory failure, fever, and an abdominal mass. PMID- 8342265 TI - Barriers to prenatal care for low-income women. AB - Inadequate prenatal care is associated with poor birth outcomes. Recognizing barriers to care is necessary to improve results. Postpartum in-hospital interviews were conducted with women admitted through emergency departments with no physician of record (n = 69) in 8 Sacramento hospitals during April and May 1991. A focus group of local obstetrician-gynecologists was used to determine physicians' attitudes about caring for low-income women. We undertook the study in response to an increased number of "no doc" births. The inability to find a physician willing to accept them was reported by the women as the single largest barrier to obtaining care, cited by 64% of women overall and 96% of those who tried but were unable to obtain care. Transportation difficulties were a problem regardless of women's success in obtaining care and were ranked as the top barrier by women who never tried to obtain care. Physicians cited administrative difficulties and reimbursement levels of Medi-Cal plus extra care requirements and resource dependency of low-income patients as barriers to caring for this population. The value ascribed to prenatal care by women and physicians' perceptions of women's attitudes about care contrasted sharply. The link between poor women and physicians providing obstetric services can be fragile. The difficulty finding physicians willing to take them indicates that these women need special support services to ensure adequate care during pregnancy. PMID- 8342268 TI - Estrogen replacement therapy for reducing cardiovascular disease. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in general and family practice. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in general and family practice that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on General and Family Practice of the California Medical Association, and the summaries were prepared under its direction. PMID- 8342267 TI - Antiplatelet therapy--Part II. AB - We summarize current information about aspirin and other antiplatelet drugs in patients with cardiac and vascular disease. For each indication, we briefly summarize the rationale for the use of antiplatelet therapy and describe the findings of relevant clinical trials. We propose recommendations for the use of these agents in clinical practice. In Part 2, we discuss the use of antiplatelet agents in coronary angioplasty, atrial fibrillation, artificial cardiac valves, stroke, and peripheral vascular disease. In Part 1, we reviewed the use of antiplatelet therapy for the primary and secondary prevention of myocardial infarction, in conjunction with coronary thrombolysis, in patients with unstable and chronic stable angina, and following coronary artery-saphenous vein bypass grafting. PMID- 8342269 TI - Sleeping position and sudden infant death syndrome. PMID- 8342270 TI - Outpatient management of asthma. PMID- 8342271 TI - Practical approach to diagnosing and treating sinusitis. PMID- 8342272 TI - Health and medical care of homeless persons. PMID- 8342273 TI - Practice guidelines movement. PMID- 8342274 TI - Universal hepatitis B childhood vaccinations. PMID- 8342275 TI - Increased surgical options for dysfunctional uterine bleeding. PMID- 8342276 TI - Changing guidelines for screening mammography. PMID- 8342277 TI - Acute dilated cardiomyopathy as a cluster in children. PMID- 8342278 TI - Overcoming the limitations of chemotherapy in the treatment of B-cell non Hodgkin's lymphomas--an approach using radiolabeled peptide ligands. PMID- 8342279 TI - Ileus and ignorance. PMID- 8342280 TI - Reserpine and thiazide for hypertension--an inexpensive therapy for older patients. PMID- 8342281 TI - Assessing CME needs assessment. PMID- 8342282 TI - Otitis externa and facial cellulitis from Oriental ear cleaners. PMID- 8342283 TI - Future directions in sickle cell disease. PMID- 8342284 TI - Singapore's solution to health care costs. PMID- 8342285 TI - The burden of reform falls again to the states. PMID- 8342286 TI - Leadership or lordship? PMID- 8342287 TI - Medical billing system. PMID- 8342288 TI - Suicide among Wisconsin elderly. AB - Suicide can be one of the most tragic events possible for an individual and family. Suicide, especially among the elderly, evokes very strong sentiments. "Assisted death," "death with dignity," "rational suicide for reasons of age," "a person's right to die," "euthanasia," and "mercy killing" are some of the phrases used to characterize one's own position or the position of those with opposing opinions. This article examines Wisconsin death certificate data for the years 1985 through 1990. PMID- 8342289 TI - Verbal communication with cuffed tracheotomy. PMID- 8342290 TI - White House meeting 'positive for physicians'. PMID- 8342291 TI - Trends in stroke mortality in Wisconsin: progress toward achieving the year 2000 objective. PMID- 8342292 TI - The effects of Medicare and Medicaid reimbursement on the financial viability of clinics and physician practices in medically under-served areas of Wisconsin. AB - A survey of 21 physicians and clinic managers located in Health Professional Shortage Areas (HPSAs) and other under-served areas in Wisconsin found that to combat increasing costs, Medicare and Medicaid discounts, charity care demands and physician recruitment difficulty, several practices rely on outside sources of funding to remain financially viable. Also, the financial viability of physician practices in under-served areas of Wisconsin is threatened more by the reimbursement rates of Medicaid and Medicare than by the provision of charity care. Though few are limiting the number of Medicare and uninsured patients they will treat, many practices have begun implementing cost-containment measures, including more strict collection policies. There are also indications of restricted access for Medicaid patients at some sites. PMID- 8342293 TI - Wisconsin physicians reach out to Nicaraguan children. PMID- 8342294 TI - John Randolph Currens, MD: 1855-1921. PMID- 8342295 TI - Metabolism of thiodiglycol (2,2'-thiobis-ethanol): isolation and identification of urinary metabolites following intraperitoneal administration to rat. AB - 1. The metabolism of thiodiglycol, 2,2'-thiobis-ethanol, was investigated following i.p. administration to rat. 2. Approximately 90% of the administered dose was excreted in the 0-24-h urine. Four metabolites were isolated by h.p.l.c. and identified by mass spectrometry. Structural assignments were confirmed by comparison with authentic synthetic standards. 3. Thiodiglycol sulphoxide was the major metabolite accounting for approximately > or = 90% of the excreted radioactivity following i.p. injection of 13C4, 35S-thiodiglycol. Thiodiglycol sulphone, S-(2-hydroxyethylthio)acetic acid and S-(2-hydroxy ethylsulphinyl)acetic acid were identified as minor metabolites. 4. Analysis for thiodiglycol by GC-MS indicated approximately 0.5-1% of the applied dose was excreted unmetabolized. PMID- 8342296 TI - Disposition of prednisolone in the course of subclinical fascioliasis in sheep. AB - 1. The in vivo disposition of prednisolone in sheep was studied before, during and after recovery from experimental hepatitis of parasitical origin (fascioliasis). 2. After i.v. administration, plasma clearance of prednisolone was increased from 0.93 +/- 0.13 l/kg per h before infection to 1.73 +/- 0.50 l/kg per h at week 21 post-infection. The steady state volume of distribution was increased from 0.45 +/- 0.08 l/kg during the control period to 1.26 +/- 0.44 l/kg at week 5 post-infection. 3. None of the prednisolone binding parameters (specific and non-specific sites) was modified, and the overall mean unbound fraction was 24%. 4. Urinary excretion of unchanged prednisolone was low and only a trace of 6 beta-hydroxy-prednisolone was identified. PMID- 8342297 TI - On the metabolism of haloperidol. AB - 1. p-Fluorobenzoyl-propionic acid, 4-(4-chlorophenyl)-4-hydroxy-piperidine, and reduced haloperidol were confirmed as metabolites of haloperidol. Their formation was catalysed by hepatic microsomes and was NADPH dependent. 2. The pyridinium metabolite of haloperidol (HP+) was identified. It is proposed that haloperidol first undergoes dehydration to form its 1,2,3,6-tetrahydropyridine analogue (HTP). HTP is then further metabolized to HP+, HTP N-oxide and its N-dealkylated product, 4-chlorophenyl-1,2,3,6-tetrahydropyridine (CPTP). HTPN-oxide was metabolized to CPTP and HTP. All these metabolites were confirmed by comparison with synthesized compounds using h.p.l.c. and h.p.l.c.-mass spectrometry. 3. Three unknown metabolites were present in microsomal metabolic incubations of haloperidol. One of them was tentatively characterized by h.p.l.c.-mass spectrometry as an oxygenated product of haloperidol, another appears to be the 2 pyridine analogue of haloperidol. The third metabolite was shown to be a neutral compound of unknown structure, which was not haloperidol N-oxide nor 4-hydroxy-4' fluorobutyrophenone. In addition, HTP was metabolized to a further unknown product with a similar u.v. spectrum to that of HTP. 4. The identification of these metabolites led to the hypothesis that the metabolism of haloperidol is similar to that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and may therefore produce motor neurone toxicity by a similar mechanism. PMID- 8342298 TI - Studies on the metabolism of a monoterpene ketone, R-(+)-pulegone--a hepatotoxin in rat: isolation and characterization of new metabolites. AB - 1. The metabolic disposition of R-(+)-pulegone (I) was examined in rats following four daily oral doses (250 mg/kg). 2. Six metabolites, namely pulegol (II), 2 hydroxy-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanone (III), 3,6-dimethyl-7a hydroxy-5,6,7,7a-tetrahydro-2(4H)-benzofuranone (IV), menthofuran (V), 5-methyl-2 (1-methyl-1-carboxyethylidene)cyclohexanone (VI), and 5-methyl-5-hydroxy-2-(1 hydroxy-1-carboxyethyl)cyclohexanone (VII) have previously been isolated from rat urine, and identified (Moorthy et al. (1989a). Eight new metabolites have now been isolated from rat urine, namely, 5-hydroxy-pulegone (VIII), piperitone (IX), piperitenone (X), 7-hydroxy-piperitone (XI), 8-hydroxy piperitone (XII), p-cresol (XIII), geranic acid (XIV) and neronic acid (XV). These were identified by n.m.r., i.r. and mass spectrometry. 3. Based on these results, metabolic pathways for the biotransformation of R-(+)-pulegone in rat have been proposed. PMID- 8342299 TI - Fungal biotransformation of organophosphines. AB - 1. The biotransformations of triphenyl phosphite and of triphenyl-, tri-n.-butyl , diethylphenyl-, and ethylmethylphenyl-phosphines by the fungi Mortierella isabellina ATCC 42613, Helminthosporium species NRRL 4671, and Aspergillus foetidus ATCC 10254, have been examined. 2. The triaryl and tri-n.-butyl substrates underwent oxidation at phosphorus in low yield, a process attributed largely to auto-oxidation under the experimental conditions used. 3. The alkyl aryl phosphines were enzymically oxidized at phosphorus, but concurrent auto oxidation also occurred. 4. Incubation of ethylmethylphenyl phosphine with M. isabellina gave the corresponding S(-) phosphine oxide in a 92% yield with an enantiomeric purity of 13%. PMID- 8342300 TI - Enantiomer-enantiomer interaction of a uricosuric antihypertensive diuretic (DBCA) in renal tubular secretion and stereoselective inhibition by probenecid in the cynomolgus monkey. AB - 1. Enantiomer-enantiomer interaction of 5-dimethylsulphamoyl-6,7-dichloro-2,3 dihydrobenzofuran-2-carboxyl ic acid (DBCA), a uricosuric, diuretic and antihypertensive agent, was studied from the pharmacokinetics of the enantiomers following intravenous injection of individual enantiomers and racemate into male cynomolgus monkeys. Also studied was the involvement of the anion transport system in the renal excretion of DBCA by comparison of the pharmacokinetics in probenecid-treated and non-treated animals. 2. Separate administration of individual enantiomers showed higher plasma concentrations of (S)(-)-DBCA than those of the antipode, at an early period after dosing. Both enantiomers disappeared rapidly from plasma with an elimination half-life (t1/2 beta) of 0.35 0.38 h. Unbound fractions were 18.9% for the (R)(+)-enantiomer and 10.2% for the (S)(-)-enantiomer. The major portion of both enantiomers was excreted by 6 h after dosing and 77-78% of the dose was recovered within 48 h, principally as the unchanged drug. Tubular secretion contributed significantly to the renal excretion of DBCA, because tubular secretion clearance values of unbound drug (CLrf,s) were 14- to 29-fold greater than creatinine clearance. 3. The presence of the antipode decreased the tubular secretion clearance (CLrf,s) value of unbound (S)(-)-enantiomer by 30%, and tended to decrease that for the unbound (R)(+)-enantiomer, although not significantly. This indicates the occurrence of enantiomer-enantiomer interaction in the process of renal tubular secretion, and the inhibition of (S)(-)-DBCA renal excretion in the presence of the antipode. 4. Probenecid treatment significantly decreased the CLrf,s of both enantiomers, and the extent of inhibition for the (S)(-)-enantiomer (53%) was significantly higher than that for the antipode (14%). These results show that renal tubular secretion of DBCA involves an anion transport system which prefers the (S)(-)-enantiomer, and that probenecid can preferentially inhibit (S)(-)-enantiomer secretion. PMID- 8342301 TI - Biological fate of sulphur mustard (1,1'-thiobis(2-chloroethane)): uptake, distribution and retention of 35S in skin and in blood after cutaneous application of 35S-sulphur mustard in rat and comparison with human blood in vitro. AB - 1. During the 6-h occluded cutaneous application of 35S-sulphur mustard vapour to rat, most of the dose, approximately 75%, passed through the skin and was systemically-distributed. Up to 25% of the 35S was retained in the skin, up to 30% was excreted in the urine and 5-8% was present in the blood, by the end of the application. 2. 35S initially declined rapidly in skin and then more slowly with a half-life of approximately 7.4 days. Some of the early loss was as sulphur mustard vapour from a possible depot of this compound which was larger with increase in dose. There was some apparent continuing uptake from such a depot into the systemic circulation. 3. The decline of 35S in blood was much slower than that from skin. About one-fifth of the original post-exposure level in the blood still present 6 weeks later. 4. The 35S in blood was mainly in the red cell contents as reaction products of haemoglobin with sulphur mustard. Its persistence in the systemic circulation, after an initial rapid decline due to its removal from the plasma, reflected the 65 day life span of these cells. Significant levels of 35S were found in the plasma only for a few days (t1/2 = 2.4 days). 5. Uptake and subsequent distribution of 35S in rat and human blood in vitro during gradual exposure to 35S-sulphur mustard using a novel method were similar. 35S in the red cells was associated mainly with the haemoglobin protein, but slightly greater binding with human, rather than with rat, plasma components was indicated. PMID- 8342302 TI - Report of the Validation and Technology Transfer Committee of the Johns Hopkins Center for Alternatives to Animal Testing. Framework for validation and implementation of in vitro toxicity tests. AB - The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technological developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial and regulatory communities, is recommended. Test validation acceptance is contingent upon broad buy-in by disparate groups in the scientific community-academics, industry and government. This is best achieved by early and frequent communication among parties and agreement upon common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction and refinement alternatives in toxicity testing. PMID- 8342303 TI - [100 years of Zeitschrift fur Orthopadie]. AB - The article affords insight into the one hundred years' history of the Journal of Orthopedics. The existing 130 volumes reflect the change in the orthopedic spectrum of illness, diagnostic investigation and treatment. Already in its first few years of existence, the journal was a forum for international exchange. Investigation of various epochs showed that the editors applied strict scientific standards in selecting the publication, despite basis changing historical conditions. They were able to prevent political interventions appreciably influencing the character of the journal. At the same time, the negative effects which the two world wars and National Socialism had on the further development of orthopedics become evident. The extent to which, as a result of these, the development of orthopedics fell behind international development could only be overcome in the last few decades. PMID- 8342304 TI - [Ultrasonography of the spine in infancy]. AB - QUESTION: Based on a standardized technic and reliable attachment of the presented structures the suitability of spinal sonography as a screening-method in newborns and infants should be estimated. METHODS: Enabled by the comparison of sonographic transverse and sagittal plains with identical anatomic sections of an infant corpse the anatomic structures of an healthy spine were associated, which was verified in the clinical use later on. RESULTS: Exemplary photographs of a collective of 50 newborns and infants reproduce the presentation of the spine found in the preparation of the corpse. The technical practicability of such an examination in clinical use was confirmed herein and it became clear that the application of this method is limited from the 6.-8. months of living on because of the increasing ossification which involves a reduction of the image quality. The deviations from the spine presentation in normal relations were shown by some ultrasound examples of malformed spines (spinal dysraphism, hemivertebrae). CONCLUSION: Reproducible attachment of the structures obviously seen with ultrasound and the clear demarcation of deformations as well as the simply practicable examination make evident the suitability of spinal sonography in newborns and infants as a noninvasive screening for the exclusion of spine malformations. PMID- 8342305 TI - [Dysphagia as a symptom of a ventral cervical prolapsed disk]. AB - Ventral osteophytes, which occur frequently, usually cause no symptoms. They are sometimes identified as the cause of dysphagia. Cervical disc prolapses which cause symptoms of dysphagia are far less common. This paper describes a patient with dysphagia in whom ventral cervical disc prolapse was finally diagnosed by MR tomography, after she had been through a "diagnostic odyssey". The result was subsequently confirmed at surgery. The relevant literature is also reviewed. PMID- 8342306 TI - [The value of diskography in disk-related pain syndrome of the cervical spine for evaluation of indications for spondylodesis]. AB - In this study the postoperative results of patients with cervical spondylodesis for "discogenic pain syndrome" were evaluated. The diagnosis "discogenic pain syndrome" as well as the pathologic segments were confirmed by cervical discography. However interpretation of the discogram as "positive" was only considered reliable when typical pain provocation through discography correlated with pathologic disc pattern ("functional test"). 38 cervical segments have been found to fulfill these criteria and were fused in 29 operative procedures (21 unisegmental, 7 bisegmental, one trisegmental). The patients were evaluated postoperative for change of symptoms, pain character and intensity, neurological deficits, working and sporting disability and mobility of cervical spine. According to the criteria of Simmons and Segil 73% of the patients showed a good to excellent result. A fair result was found in 23.2% and an unsatisfactory result was seen in 3.8%. In the literature a good to excellent outcome is seen in 30 to 46% in similar patients groups after cervical fusion without preoperative assessment by discography. PMID- 8342307 TI - [10-year follow-up of C3-C7 cervical laminectomy for intramedullary grade I astrocytoma]. AB - In an eight years old boy we operated an intramedullary astrocytoma grade I and reimplanted the laminae C4-7 en bloc. A good stability was achieved. Ten years later only one segment remained intact, the others showing spontaneous fusion as a major draw back. This is possibly due to subperiostal dissection and bracing. No spinal stenosis occurred. An overuse of the remaining disc C4/5 might lead to a secondary degenerative stenosis. The operation is simple and might avoid swan neck deformity in children after large decompression of dorsal structures. PMID- 8342308 TI - [Initial experiences with subcutaneous Harrington distraction without spondylodesis in scoliosis]. AB - We report on a special method in the treatment of scoliosis using subcutaneous Harrington-distraction without spondylodesis. We operated 14 patients in all who were between 7 and 12 years old, in average 10 2/12 years Indication is made if scoliosis is extremely progressive, if Cobb's measure is above 50 degrees, after unsuccessful conservative treatment also including orthosis and physiotherapy, or if patients appeared to late in our department. In this technique only two incisions to make are necessary to place the Harrington roots to the cranial and caudal end of the scoliosis curve. The Harrington root can be 'needled' in subcutaneously. When in times of further growth the amount of correction gets noticeably lost the cranial hook could be tightened or the Harrington root could be changed easily. We need an orthosis (Cheneau or Milwaukee) for after treatment until in a final operation with spinal fusion is made. This method has showed good results although we had to cope with a bad prognostic starting position. PMID- 8342309 TI - [Comparative biomechanical studies following automated percutaneous nucleotomy and diskotomy]. AB - APLD is considered as the last step of conservative treatment for lumbar disc herniation assuming that a negative biomechanical effect of APLD is not expected. Biomechanical effects of APLD were investigated in comparison to open discectomy. APLD decreased disc height less than open discectomy and increased instability and flexibility less. The position of the center of rotation was not significantly altered. PMID- 8342310 TI - [Long-term results following percutaneous facet coagulation]. AB - 93 patients with a mean follow up of 73 months (30-133 months) after lumbar percutaneous radiofrequency denervation (PRFD) were evaluated. Mean age of the patients at time of surgery was 47 years (18-76 years). 54 patients had no lumbar spine surgery prior to facet denervation, 32 patients had one or multiple disc surgery prior to denervation, and 7 patients had spinal fusions. 51 patients were in the process of early retirement or already retired at time of surgery. Out of all 93 patients only 50% had significant pain relief immediately after PRFD. 3 months after PRFD the success rate dropped down to 38%. 6 years after surgery only 25% of all patients had long lasting good results. Patients who were pain free after facet infiltration had significant better initial results, but were similar to the others after 6 years. 6 out of 7 patients after lumbar spinal fusions demonstrated bad results. The worst results had those patients who had applied for early retirement (workmens compensation cases). In this group the recurrence rate was 74% 6 years after surgery. We found no correlation between the surgeon and the outcome. CLINICAL RELEVANCE: Without pain reduction after facet infiltration the success rate after PRFD is low. Spinal surgery prior to PRFD significantly reduces the success rate. The worst prognosis have workmans compensation cases. The recurrence rate is high within the first 6 months after PRDF. PMID- 8342311 TI - [Effects of inflammation-induced spinal fusion of the lumbar area on movement of the lumbar spine]. AB - Lateral x-rays of the lumbar spine in standing position and functional flexion extension roentgenograms of 21 patients with spontaneous fusion within the lumbar area after spondylitis were checked related to kyphosis of the block, lordosis and mobility of the lumbar spine and the single discs, and the appearance of degenerative spondylolisthesis. 76% demonstrated degenerative spondylolisthesis of the neighbouring discs, the half of them more than 5 mm with a significant higher number of segmental loosening of the disc caudal to the fusion. The kind of instability is a pseudo-spondylolisthesis (Junghans 1930) above and a retrolisthesis below the fused area. No higher mobility (no significant difference of mobility between the two cranial and the two caudal discs) can be seen as cause of this behaviour. The increased lordosis of the caudal segments is discussed to be the cause of the retrolisthesis distal the fusion. Altogether, kyphosis of the fused area leeds compensatory to a higher grade of lordosis in the mobile part of the lumbar spine without reaching the physiological lordosis of total lumbar spine. Kyphosis of the block does not influence mobility of the discs or the total lumbar spine, but increases significantly the rate of degenerative spondylolisthesis in the vicinal segments. These results suggest the operative reduction of lumbar lordosis in cases of kyphotic spondylitic destruction within the lumbar or thoracolumbar region in younger patients. PMID- 8342312 TI - [Spinal surgery on patients with myelomeningocele. Results 1971-1990]. AB - Between 1971 and 1990 33 kyphectomies were performed at the Orthopaedic Hospital, University of Heidelberg. The average age at time of surgery was 5 years/5 months; the follow-up period was 5 years. The best results were obtained in the group with congenital rigid kyphosis. A marked postoperative deterioration was considered in patients with a flexible paralytic kyphosis, probably due to a too short area of fusion. In 19 patients the correction of the kyphotic deformity was the prerequisite for being provided with orthotic devices. The most serious complication was the intraoperative death of 3 patients. It can be presumed, that after transection of the spinal cord a non-functioning CSF-shunt lead to an acute elevation of the intracranial pressure. Therefore an adequately functioning shunt must be secured preoperatively. PMID- 8342313 TI - [Does geometry of the lumbosacral inclination have an effect on the etiology of isolated osteochondrosis of L5/S1?]. AB - Men and women with isolated osteochondrosis L5/S1 (excluding transitional anomalies) were compared against a corresponding group of healthy volunteers to see whether there is any geometric or statistical evidence that might constitute predisposing factors for isolated osteochondrosis L5/S1. Arithmetic means, variances, standard deviations, and correlation coefficients were calculated for all the characteristics determined for the two groups. Multiple linear discriminant analysis was used to try to reproduce any classifications our groupings of the characteristic bearers on the basis of their characteristics. It was found that the position of the sacrum in the pelvis and the extent of lumbar lordosis play a major role. To detect a predisposition for isolated osteochondrosis L5/S1, it is thus necessary to evaluate: the position of the sacrum with regard to the pelvis and the degree of lumbar lordosis-excluding that of the fifth lumbar vertebra-in the angle system. This evaluation can be performed by measuring the dorsal inclination of the sacrum (the delta angle) and the Albrecht inclination. PMID- 8342314 TI - [Assessment of surgically treated vertebral fractures of the thoracic and lumbar spine without neurological complications]. AB - The progress of surgical treatment of spine fractures leads to new problems in the assessment of these patients. Possible consequences of this treatment are discussed (especially approach-caused faults in muscle or pulmonary function). Beside the length and localisation of the fusion the strain on the adjacent movement segments have to be considered. The different function of the different regions of the spine is also represented. The possible "MdE" is discussed under consideration of the above criteria. PMID- 8342315 TI - [A case of bilateral isolated talonavicular synostosis in childhood--observations of tarsal joint function and functional adaptation of the proximal ankle joint]. AB - A rare case of bilateral isolated coalition of the talonavicular joint with ball and socket ankle joint is presented. Range of motion of the subtalar joint and hindfoot mobility were measured intraoperatively. The following conclusions may be drawn on development and function of the ankle joint complex: Isolated talonavicular synostosis in the growing foot results in marked impairment of subtalar range of motion. The development of a ball and socket ankle joint may be caused thereby, if tarsal hypomobility becomes effective at an early stage of growth. PMID- 8342316 TI - [The tripod support of the foot. An analysis of pressure distribution under static and dynamic loading]. AB - A "tripod" loading of the human foot, as it is mentioned in some textbooks, was not found in a pressure distribution study with 111 adults. For bipedal standing as well as walking peak pressures beneath the 3rd metatarsal head were substantially higher than under the metatarsal heads I and V. Correlation analyses demonstrated that the pressure distribution during standing reveals only little information about the dynamic loads under the foot during gait. Gender differences in the load bearing behavior of the foot as well as significant correlations of peak pressures towards body weight and foot contact area were found. PMID- 8342317 TI - [Assessment of congenital foot deformities]. AB - The assessment of congenital foot deformities is only relevant in the context of German legislation (SchwbG) defining disability and fitness for military service. All assessments of congenital foot deformities should be based on the twin concepts of function and capacity to withstand stress. However, assessments with regard to the degree of disability and fitness for military service will occasionally differ. This article discusses the various congenital foot deformities individually, allocating them to the respective degrees of disability [as laid down in German law]. The classification may serve as a guide for consultants within the context of disability legislation and for ascertaining fitness for military service in accordance with the "Central Standing Orders" of the Federal German armed forces. PMID- 8342318 TI - Comparison of humoral immune responses to trivalent influenza split vaccine in young, middle-aged and elderly people. AB - A total of 296 volunteers in five different groups were immunized with one dose of the commercial 1991-1992 trivalent split influenza vaccine formulation A/Singapore/6/86 (H1N1), A/Beijing/353/89 (H3N2) and B/Yamagata/16/88. The groups differed in age (young adults, middle-aged and elderly) and history of previous vaccination. Antibodies were determined in pre- and postvaccination sera by haemagglutination inhibition assay and the results were evaluated as geometric mean titre, mean fold antibody increase, protection and response rates. No significant age-related differences among the protection rates were found. The proportion of vaccinees with antibodies > or = 40 ranged between 70 and 95%. Compared with the H3N2 and B components the antibody response to the H1N1 component was low. Residents of a nursing home fully vaccinated the previous year developed 7.6-8.4-fold antibody increases and showed 96-100% protection rates. PMID- 8342319 TI - Studies on reactogenicity and immunogenicity of attenuated bivalent cold recombinant influenza type A (CRA) and inactivated trivalent influenza virus (TI) vaccines in infants and young children. AB - Fifty-two infants seronegative to or without prior infection with influenza type A viruses were enrolled in a study to evaluate reactogenicity and immunogenicity of three bivalent cold recombinant type A (CRA) and two trivalent inactivated influenza (TI) vaccines. Controls consisted of infants receiving normal saline by nose drops (Pli.n.) or intramuscularly (Pli.m.). CRA and TI vaccines were monitored for local and systemic reactions after vaccination. Serum specimens obtained prior to and 6 weeks postvaccination were analysed for neutralizing antibody to influenza H1N1 and H3N2 viruses. CRA vaccines and Pli.n. recipients had similar numbers of acute respiratory infections and comparable rates of illnesses during the trial. Significantly fewer CRA vaccinees without an intercurrent viral infection had fever (0/16 versus 4/10, p = 0.04) and cough (4/16 versus 9/10, p = 0.002) than CRA vaccinees with a confirmed intercurrent viral infection. Recipients of TI vaccine and Pli.m. did not develop reactions at the injection site. For each of the CRA vaccines tested, a dominant CRA virus was identified. The dominant CRA viruses were isolated from a greater number of infants or for a longer duration than the non-dominant CRA viruses. All 14 non dominant CRA viruses were recovered from infants within the first week after vaccination; 24 of 77 dominant CRA viruses were recovered more than 7 days after vaccination. The immunogenicity of CRA vaccines was not affected by a confirmed intercurrent viral infection or low titres of influenza-specific antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342320 TI - Correlation of antibody titres induced by vaccination with protection in mouse typhoid. AB - The ELISA method was used to titrate the humoral immune response in vaccinated mice. When mice were given two doses of a heat-killed salmonella vaccine 6 days apart, there was a steady but low-level increase of antibody synthesis. In contrast, if a booster vaccination was administered 21 days after the primary inoculation, the anamnestic response produced a significantly greater antibody titre, rapidly reaching its peak within 10 days. Such a heightened humoral response induced in the genetically susceptible C57BL/6J mice also coincided with effective protection against an otherwise lethal challenge with Salmonella typhimurium. PMID- 8342321 TI - Single capripoxvirus recombinant vaccine for the protection of cattle against rinderpest and lumpy skin disease. AB - A recombinant capripoxvirus has been constructed containing a full-length cDNA of the fusion protein gene of rinderpest virus. The gene was inserted in the thymidine kinase gene of the capripox genome under the control of the vaccinia virus major late promoter p11 together with the Escherichia coli gpt gene in the opposite orientation under the control of the vaccinia early/late promoter p7.5. A vaccine prepared from this recombinant virus protected cattle against clinical rinderpest after a lethal challenge with a virulent virus isolate. In addition, the vaccine protected the cattle against lumpy skin disease. PMID- 8342322 TI - Protection of mice from inhaled ricin by vaccination with ricin or by passive treatment with heterologous antibody. AB - Mice were vaccinated subcutaneously with 25 micrograms kg-1 of ricin in the presence of Freund's complete adjuvant or Ribi adjuvant, followed by a boost 14 days later with 50 micrograms kg-1 ricin in Freund's incomplete adjuvant or Ribi adjuvant, respectively. Three subsequent boosts at 28-day intervals with 25 micrograms kg-1 ricin yielded high anti-ricin antibody titres as determined by ELISA. Vaccinated animals were exposed to an aerosolized LD99 dose of ricin. With the exception of one death not attributable to ricin intoxication, all vaccinated mice survived the lethal aerosol exposure. In addition, a passive protection regimen was evaluated in mice pretreated with 100 micrograms purified goat anti ricin IgG administered intravenously, and then challenged with ricin intravenously. All were resistant to 125 micrograms kg-1 of ricin, a dose greater than 25 times the intravenous lethal dose. Mice injected intravenously with 5 mg of the same IgG were protected from a lethal aerosol challenge. These results indicated that it is possible to protect animals from inhaled ricin by vaccination or passive administration of specific antibodies. PMID- 8342323 TI - Immunogenicity of wild-type and vaccine strains of Japanese encephalitis virus and the effect of haplotype restriction on murine immune responses. AB - The Chinese live attenuated Japanese encephalitis (JE) virus vaccine clone SA14 14-2 produced in primary hamster kidney (PHK) cells has been adapted to primary dog kidney cells (PDK) for use as a live attenuated human vaccine. In this study we have compared the immunogenicity in mice of SA14-14-2 (PDK) and SA14-14-2 (PHK); also included was the wild-type parent to the vaccine clones, SA14, and another wild-type JE virus strain Nakayama (original). It was found that Balb/c (H-2d) mice given a single dose of 10(3) or 10(6) p.f.u. of live SA14-14-2 (PHK) virus elicited a superior neutralizing (N) antibody response as compared to the same dosages of live SA14-14-2 (PDK) virus. However, if the vaccine clones were inactivated and administered in a two-dose regime the N antibody response elicited was similar for the two viruses. This observation may be explained by differences in the replication efficiency in vivo of the respective vaccine clones. The humoral immune response to all the virus strains in this study elicited by different inbred mouse strains each carrying a discrete haplotype (Balb/c (H-2d), C3H (H-2k), C57BL/6 (H-2b)) were also assessed using haemagglutination inhibition (HAI) and N assays. Viruses were shown to elicit patterns of high and low N-antibody response depending on the major histocompatibility complex (MHC) make-up of the mouse strains. However, the patterns did not necessarily coincide when HAI and N titre reactivity patterns were compared for the same virus strain. PMID- 8342324 TI - Clinical and serological evaluation of a Pasteurella haemolytica A1 capsular polysaccharide vaccine. AB - The purified capsular polysaccharide (CPS) of Pasteurella haemolytica A1 was examined for its ability to protect cattle from experimental challenge with logarithmic-phase P. haemolytica. Several preparations of P. haemolytica antigens were utilized in the experiment including CPS, log-phase P. haemolytica culture supernatant, P. haemolytica recombinant leucotoxin (rLKt) and various combinations of the above. CPS alone or in combination with culture supernatant or rLkt elicited no protection; rather, administration of CPS was associated with a high incidence of anaphylaxis (36% of calves). Although a classical biphasic humoral immune response to CPS could be detected in all calves that received this compound, this T-dependent response was not correlated with resistance to experimental challenge. The complexity of protective immunity in pneumonic pasteurellosis is emphasized by this study, and clinical anaphylaxis associated with response to CPS may be implicated in the pathogenesis of disease. PMID- 8342325 TI - Expression of a recombinant Entamoeba histolytica antigen in a Salmonella typhimurium vaccine strain. AB - The expression of a major surface antigen of the intestinal protozoal parasite Entamoeba histolytica in an attenuated Salmonella typhimurium vaccine strain is described. A polymerase chain reaction fragment derived from cDNA encoding the serine-rich Entamoeba histolytica protein, SREHP, was introduced into S. typhimurium chi 3987 (delta cya delta crp delta asd) using a plasmid expression vector (pYA292) containing the aspartate semialdehyde (asd) gene. S. typhimurium expressing recombinant SREHP as a SREHP/maltose binding protein fusion protein was administered orally to mice and gerbils (an important animal model for E. histolytica infection) and was recovered from splenic tissue in both species. Our study demonstrates the feasibility of expressing recombinant amoebic proteins in attenuated S. typhimurium strains, and shows that vaccine strains of S. typhimurium can successfully infect the gerbil, a widely used model for amoebic liver abscess and intestinal amoebiasis. PMID- 8342326 TI - Immunoadjuvant activity of a liposomal IL-6 formulation. AB - The adjuvant effect of interleukin 6 (IL-6) entrapped in liposomes was evaluated using a 65 kDa heat shock protein as a model antigen. The secondary humoral immune response either to antigen alone, or incorporated into liposomes, and the effect of IL-6 entrapped in liposomes, on this response were studied in Balb/c mice. The adjuvanticity of these formulations was compared with that of potent adjuvants such as Ribi and dimethyldioctadecylammoniumbromide (DDA). The importance of IL-6 during adjuvant activity was supported by the observation that high serum IL-6 levels were induced in Balb/c mice by all members of a panel of adjuvants tested. Following incorporation into liposomes, IL-6 retained its full biological activity, as shown by its capacity to sustain growth of the IL-6 dependent B9 cell line. At antigen dosages where Ribi and DDA gave minimal or no secondary antibody titres, incorporation of antigen into liposomes resulted in measurable secondary antibody titres. Interestingly, this adjuvant activity was significantly enhanced when liposomes containing IL-6 were co-injected with the liposomal antigen formulation. These results illustrate the potential adjuvant properties of this formulation, which seem especially useful for vaccines containing weak or non-immunogenic antigens. PMID- 8342327 TI - [Perinatology. Fetal origin of diseases in adults]. AB - Perinatal medicine is mostly interested in the normal development of the growing fetus. Perinatal care is becoming even more important, since a disorder in fetal development, due to an abnormal intrauterine milieu, results in problems during infancy and adult age. There is clear evidence that this is the case in diabetes and pregnancy and in intrauterine growth retardation. PMID- 8342328 TI - [The serological diagnosis of gastrointestinal nematode infections in cattle]. AB - Ostertagia ostertagi and Cooperia oncophora are widely distributed and are the most important parasites affecting young bovine livestock. Therefore, there is a substantial need for sensitive and specific parameters in support of their diagnosis, especially for sub-clinical disease correlated to production loss. In this review, the value and the application as a diagnostic tool of pepsinogen, gastrin and antibody response are discussed. An increase in pepsinogen or gastrin reflects mucosal damage caused by an Ostertagia infection. Some controversy exists about the level of pepsinogen and gastrin, which may be considered indicative for the diagnosis of clinical and sub-clinical ostertagiasis. Pepsinogen levels between 3,000 tot 4,000 mU tyrosine are regarded indicative for subclinical disease, values in excess of 5,000 mU tyrosine are considered significant for diagnosing clinical disease. For gastrin, it is suggested that based on group means, values of 400 pg/ml are indicative for subclinical parasitic disease in calves with reduced daily weight gain, while threshold levels of > or = 1000 pg/ml gastrin are representative for clinical ostertagiasis. Antibody responses to Ostertagia and Cooperia can be assessed using the enzyme immunoassay (EIA). Until now, mainly crude worm extracts have been used as antigen source in the EIA. They are not species-specific as discussed experiments provide evidence of a close relationship between the onset of parasitic disease and the evolution of the group mean parameters. However, data demonstrate serious variations between animals, which impede a reliable individual diagnosis. For longitudinal epidemiological studies especially pepsinogen and gastrin have proven their value, exhibiting fast fluctuations induced by infection or as a result of treatment. Conversely antibody levels were found to be more stable and therefore are useful in large cross-sectional studies, enabling a rough assessment of the degree of infection. PMID- 8342329 TI - [Theory and practice of medicine: levels of knowledge and clinical medicine as a cultural institution]. AB - The author discusses the contents of his book "The inside of medicine" which appeared at the end of 1990 (it is written in dutch). The book aims to acquire a view how the metamorphosis of theory and practice of medicine as to size and diversity in the past fifty years came about. Also health care developed into a social right, and became a cultural institution. The book is not meant as a history of medicine of that period, but rather as a history of ideas illustrated with examples. The author feels qualified to do so, because he was actively involved with research during those years. Before World War II his activities were during ten years limited to laboratory research (biomedical) in the Netherlands, U.S.A. and finally at the Pasteur Institute in Paris. Residencies in internal medicine followed and qualification for this specialty. From 1948-1983 he held a chair at Leiden University in Internal medicine and concentrated his research on endocrinology and metabolic diseases (patient centered research). He was Founding Dean of the Rotterdam Medical Faculty for 5 years. Since the beginning of the 20th century it is accepted that illness in general is multifactorially determined. However research about illness is still dominated by the Newtonian unidirectional paradigm of cause to effect, which leads to mechanistic thinking. Obtained data are followed further by the same method, through different levels of knowledge from symptom to morphology and to pathophysiology, and finally to the molecular level. Undoubtedly much has been achieved. The integrated approach, reflecting reality, often characterized by the term of the bio-psycho-social view, was hardly used. It is frequently suspected that advances are disappointing in diseases like atherosclerosis, or the deviating course of disease and recovery in advanced age etc. because of that reason. Molecular biology is at a too early stage of development that reasoning upwards to the "lived human body" is possible. The author feels that there are signs of changing the approach and paradigm at present. Some examples will be discussed. PMID- 8342330 TI - On the regulation of the plasminogen activator inhibitor-1 gene expression. AB - Plasminogen activators and their inhibitors play a pivotal role in maintaining the hemostatic balance in blood and also in other proteolytic processes such as cell migration and tumor invasion. The main physiological inhibitor of the plasminogen activators is plasminogen activator inhibitor-1 (PAI-1). The effect of PMA on the endogenous PAI-1 production and on the expression of transfected promoter/reporter gene constructs was studied in HUVEC and in the HT1080 and HeLa cell lines. Addition of PMA (> or = 10 nM) to monolayer cell cultures induced a 2 to 5.5-fold increase of PAI-1 antigen production within 8-24 h. In HUVEC, PMA (160 nM) induced both the 2.4 kb and 3.4 kb mRNA species of PAI-1: 3.1 +/- 1.1 and 1.7 +/- 0.8-fold (n = 6), respectively, within 8 h. Run-on experiments confirmed that this increase is at least partially mediated by increased gene transcription. When HUVEC, HT1080 and HeLa, transfected with an 826 bp or a 336 bp PAI-1 gene promoter fragment, were stimulated with 160 nM phorbol 12-myristate 13-acetate (PMA), the CAT activity was induced 4-, 3.5- and 10-fold respectively for both constructs, revealing that PMA responsive sequences are present in the proximal 336 bp of the PAI-1 promoter. Substitution mutations in the regions encompassing nucleotides -78 to -69 (TGGGTGGGGC) or -61 to -54 (TGAGTTCA), but not in the regions -155 to -149 (TGCCTCA) or -84 to -76 (AGTGAGTGG) reduced this induction. Gel electrophoresis of double stranded -65 to -50 oligonucleotides of the PAI-1 promoter region and nuclear extracts from HeLa cells produced a gel shift pattern, similar to that obtained with a AP-1 consensus oligomer, and excess unlabeled AP-1 oligomer reverted binding suggesting that this region of the PAI-1 promoter is an AP-1-like binding site. Gel electrophoresis of double stranded -82 to -65 oligonucleotide with HeLa nuclear extracts revealed a gel shift pattern of three bands. Sp1 consensus oligomer competed with the binding of two of these bands and AP-2 consensus sequence oligomer with the binding to the third band. The -82 to -65 oligomer also bound to purified AP-2 and Sp1 proteins. Southwestern blotting of HeLa nuclear extracts revealed that the labeled oligomer covering region -82 to -65 bound the proteins with molecular weights of 52 kD and 72 kD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8342331 TI - [Reliability of the Child Behavior Checklist in a population of 6 to 8-year-old special education students]. AB - 66 children attending first grade at a special school for educationally subnormal children were examined medically and psychologically. Classification was done according to ICD-10. In addition, the parents were asked to rate their children's behavior with the "Child Behavior Checklist" by Achenbach and Edelbrock. The most common symptoms rated in this group of 6- to 8-year-old children were lack of concentration, speech and language problems, hyperactivity, demand for attention and arguing. The mean total score (cut-off score: 30) and the number of crucial items (cut-off score: at least two crucial items) differed significantly between the children with and those without psychiatric disorders. No significant correlation was found between the mean total score or the number of crucial items and the sex of the children or the other axes of the Multi-axial Classification of Child Psychiatric Disorders. PMID- 8342332 TI - [Overprotectiveness as a coping reaction in intensive physical therapy]. AB - 25 mothers of children with cerebral palsy who were doing daily intensive physical therapy (Vojta) completed questionnaires concerning their child's temperament, parental attitudes and how they coped with everyday problems. Their responses were compared to those given by mothers who were not under the stress of conducting therapy. The results revealed compensatory coping processes: Mothers doing therapy try to compensate for their child's stress by being overprotective in ambiguous everyday situations. PMID- 8342333 TI - [Dyssocial disorders of adopted adolescents--a clinical, empirical study]. AB - The literature indicates that adopted adolescents with conduct disorders are overrepresented in psychiatric treatment facilities for children and adolescents. In the present study adopted adolescents with conduct disorders and non-adopted adolescents with conduct disorders were compared with regard to biological and psychosocial risk factors known to play a role in the development of such disorders. The groups were carefully matched for age and sex. The results showed that the adopted subjects were a distinct group with a significantly lower number of risk factors for the development of conduct disorders. This suggests that the adoptive situation has a role in pathogenesis. PMID- 8342334 TI - [Psychoneuroimmunology]. PMID- 8342335 TI - [Formation of self concept in the transition from adolescence to adulthood. An empirical comparative study of psychiatric patients and healthy control probands]. AB - The psychosocial development of psychiatrically ill and mentally healthy young adults is being explored in a series of comparative studies based on developmental tasks typical of this age. In a first study a patient group was compared with a control group with the Offer Self-Image Questionnaire as an indicator of patterns of psychosocial adaptation thus far. The patients showed significantly poorer adaptation on 10 dimensions of psychosocial life. In relation to a representative sample of young adults they especially reported disturbances in their own personality development and in family relations, but judged their adaptation to norms for behavior in public as less impaired. The nonpsychotic patients had a significantly less favorable pattern of self-concepts than the psychotic patients. The patients with affective disorders had a relatively healthy profile of psychosocial development compared with the schizophrenic patients. There was no significant difference between patients with schizophrenia of the disorganized type and other schizophrenic patients. There was a close relationship between subjective measures of self-concept and objective measures of psychosocial development, e.g. premorbid adaptation and current psychosocial development, e.g. premorbid adaptation and current psychosocial competence, in the different subgroups. The findings on self-concept seemed to be largely independent of the present severity of psychopathology. PMID- 8342336 TI - [Effect of timing and chronicity of stressors on the emotional development of children and adolescents. Results of a prospective epidemiologic longitudinal study of 8 to 18 years]. AB - In a prospective epidemiological study with assessments at ages 8, 13 and 18 it could be demonstrated that if all risk factors are analyzed at the same time recent stressors are more important than stressors and disturbances in early childhood. But from a chronological point of view early stressors were found to be at least as important as later ones because the early stressors play a role in the development of some of the later ones. The effects of stressors were sex specific to some extent: Boys were more seriously affected when of elementary school age, whereas girls were more affected in early childhood and in adolescence. Chronic stress proved to be more important than acute life events, the later being not only a cause but also a consequence of emotional disturbances. Children with early disturbances sometimes even had lower rates of disorders in adolescence if they had been brought up in an overprotective manner. PMID- 8342337 TI - [Documentation of psychopathologic findings: a procedure for the evaluation of psychological disorders in children and adolescents]. AB - A standardized documentation system for psychopathological findings allowing an assessment of psychiatric disorders in children and adolescents after clinical evaluation of the patient and his or her caregivers is presented. The symptomatology during the previous few months and the symptoms seen during the examination are rated separately. Altogether 113 items in 16 areas are assessed. In addition, motivation to participate in treatment is judged and a global assessment is made of symptom severity. A number of facilities are already employing this documentation system in their routine clinical work. In a first study 597 patients from a routine clinical population seen consecutively were assessed at the start of treatment. As expected, the most commonly recorded symptoms were those of expansive behavior. Such symptoms were seen much more rarely during the evaluation than outside this situation. The documentation system for psychopathological findings complements diagnosis by category according to ICD with a phenomenological description of psychiatric disturbances on the level of single symptoms. It enables simple and economical documentation of clinical findings after evaluation of the patient and his or her caregivers. PMID- 8342338 TI - [Peripheral neurogenic tumors--surgical therapy of neuroblastoma. Review and personal results]. AB - From January 1, 1982 to November 1, 1992 24 patients suffering from neuroblastoma were operated in the course of a neuroblastoma study at the Department of Surgery, Cologne University. 23 patients were in advanced stages 3, 4 and 4s. In 13 cases the initial operation was prior to applying chemotherapy, whereas in 10 cases chemotherapeutical treatment had taken place before. As a result of preoperative chemotherapy operation time and blood loss could be reduced, respectively, and despite delayed operative treatment a better demarcation of the tumor and an easier preparation were seen. Due to the preoperative treatment, tumors could be operated on more radically without increasing the rate of complications. Utilizing all possible surgical means, secondary and tertiary operative procedures and chemotherapeutical treatment. all patients in stage 2, 3 and 4s survived with safe remission. Nine of the fifteen patients in stage 4 died due to side effects from bone marrow transplantation or from recurrent neuroblastomas and not because of the surgical procedures. In the light of existing current multicenter neuroblastoma studies stage oriented surgical and chemotherapeutical concepts were developed, that are presented in this paper. PMID- 8342339 TI - [Thoracoscopic interventions]. AB - The technique of minimal invasive surgery has successfully been introduced into the area of thoracic surgery. Surgery of the intrathoracic organs may now be performed without compromise of respiratory mechanics, thus allowing the operative treatment of an ever widening range of pathological conditions. An analysis of our experience (287 thoracoscopic interventions in the last three years) reveals that the diverse procedures performed on the pleura (pleurectomy and pleurodesis), on the lung (wedge resection, fistula closure and ligature of parenchymatous leaks) and on other defined anatomical structures such as the sympathetic nerves or the thoracic duct, are effective in the therapy of intrathoracic disease. The most important pathological conditions which may be treated by thoracoscopy are listed. The range of complications and their causes, which developed in 8% of all procedures, are discussed. The current limitations of this method are defined in the context of the situations where thoracoscopy was discontinued (9 times), a thoracotomy performed (17 times) or a further procedure became necessary (14 times). Current developments and innovations are summarized by a short review of the literature. PMID- 8342340 TI - [Laparoscopic operations of the bile duct]. AB - Laparoscopic common bile duct exploration offers the possibility of complete minimal invasive therapy of biliary stone disease with respect to the anatomical structures of the papilla Vateri. In spite of generously indicated preoperative ERC, we found in 23 of 376 laparoscopic cholecystectomies unsuspected common bile duct stones by intraoperative in principle cholangiography. 8 patients with known common bile duct stones got a complete laparoscopic therapy. Balloon-dilatation of the ductus cysticus up to 5 mm is followed by laparoscopic choledochoscopy via the cystic duct. Small stones are washed into the duodenum or extraced retrogradely via the cystic duct. For bigger stones the intracorporeal lithotripsy is available, the stone scrap is washed either into the duodenum or is sucked off via the cystic duct. Laparoscopic choledochotomy is indicated for multiple big or proximally fixed stones. In this way stone extraction can be effectively performed, incarcerated stones are treated by additional lithotripsy. A microdrainage of the common bile duct or a T-tube drainage secures the bile flow until restitution of papillary function. The common bile duct is sewn by running suture. In the case of regular cholangiography the microdrainage can be removed on the third postoperative day. In 96% of the laparoscopic cholecystectomies intraoperative cholangiography was possible. 3 of 21 patients with transductus cysticus-exploration had to undergo postoperative EPT due to residual stone fragments. 6 laparoscopic choledochotomies showed the efficacy of the endoscopic operation technique, demonstrating the probability of complications in the postoperative period to be equivalent to that of conventional operations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342341 TI - [Sequelae of cholecystectomy--a prospective study]. AB - In a prospective study designed to assess the situation following cholecystectomy carried out at the Department of Surgery of the University of Freiburg, 105 patients were examined between August, 1988 and December, 1989. Out of 80 patients who were followed up, 64 had undergone cholecystectomy alone and the remaining 16 had been additionally subjected to exploration of the common bile duct. 80% of the patients reported that their preoperative symptoms had disappeared altogether, 8% admitted some improvement and 10% complained that their condition was unchanged. Specific questioning resulted in the reporting of persistent symptoms in 54%, and these consisted mostly of general complaints such as dyspepsia, flatulence, food intolerance and dull upper abdominal pain. These complaints were vanished or appeared with equal frequency following operation. Objective clinical findings could not be confirmed. Comparison between the pre- and postoperative signs in these patients established a statistically significant correlation (p < 0.05) between the patient's age and the severity of the preoperative symptoms on the one hand and a satisfactory postoperative outcome on the other. This also applied to patients for whom an examination of the bile duct was necessary. PMID- 8342342 TI - [Complications of intramedullary nailing and their prevention]. AB - Interlocking nailing technique offers a wide variety of indications which are associated with an increased risk of complications. A consecutive series of 208 cases were analyzed and possible complications, how to avoid them and recommendations for treatment are given. The complications were divided into common complications--like infection, pseudarthrosis, malrotation, compartment syndrome, disorders of the arterial and venous system, neurological deficts and fat embolism--as well as into specific complications--like malreduction of the fracture, malpositioning of the guide wire, splitting fragments and problems with nail insertion and with the locking bolts. There was a 8.7% common complication rate. Specific complications occurred intraoperatively in 3.5% and postoperatively in 11% of call cases. This seems to be a high rate which is decreasing by progressive experience of the surgeon. In many cases of shaft fractures interlocking nailing technique is the method of choice. PMID- 8342343 TI - [Eight years experience with the "Erlangen Model" titanium prosthesis--results of cementless implantation of 250 hip prostheses]. AB - Between March 13, 1984 and March 28, 1988, 233 patients (age range from 21 to 73 years) with osteoarthritis of one or both hips were treated with the uncemented hip replacement "Erlanger Modell" (Prof. H. Beck/P. Brehm Chirurgie-Mechanik GmbH). The cause of the osteoarthritis was variable. Hip replacement was carried out for the following conditions: rheumatoid arthritis including ankylosing spondylits (n = 29), aseptic necrosis of the femoral head including posttraumatic and idiopathic forms (n = 17), osteoarthritis of unknown origin (n = 111), osteoarthritis following dysplasia or subluxation of the hips (n = 56) and loosened cemented hip prostheses (n = 37). Full weight bearing was not permitted for 50 days postoperatively, but mobilization and isometric exercises began 2 days after operation and isotonic exercises are introduced later. Complications included fracture of the femoral shaft during operation (3.3%), fracture of the femoral shaft postoperative (1.6%), dislocation (0.8) and infection early after operation (0.4%) and aseptic loosening (3.7%). Our results of 233 patients (250 joints), ranging from 4 to 8 postoperative years giving an average of 5.3 years, are encouraging. Good results based on patients satisfaction were obtained in 95.2% (83.8% after revision) and poor results in 1.0% (2.7% after revision). 3.8% (13.5 after revision) judged their situation as unchanged. 93.3% of the patients can walk without hooked stick (53.3% after revision), 90.2% of the patients can walk more than 1000m (69.4% after revision). PMID- 8342344 TI - [Osteosynthesis of subtrochanteric femoral fractures with the dynamic condyle screw]. AB - The dynamic condyle screw was originally designed for osteosynthesis of distal femoral fractures. Because of more favourable biomechanical facilities compared with the condyle plate we have been used the implant since 1987. This investigation is based on 40 patients with pertrochanteric, subtrochanteric as well as proximal diaphyseal fractures. The majority of the patients were mobilized early and reached full weight bearing latest after 3 months according to the fracture type. The most severe complications appeared with subtrochanteric fractures with lack of medial cortical support. There was a broken plate in 2 cases and a secondary spongiosa plastic was necessary in 3 cases to ensure bony consolidation. As the point of this investigation we will see a wider indication for primary spongiosa plastic and early secondary spongiosa plastic. PMID- 8342345 TI - [Stabilization of 150 unstable spinal injuries with the Cotrel-Dubousset instrument--analysis of results]. AB - The present study is a retrospective analysis of spinal fracture treatment with the Cotrel-Dubousset instrumentation technique. 150 unstable injuries of the spine were treated with the CD implant at the University of Louisville--Level I Trauma Center--between February 1985 and March 1989. There were 67 burst fractures, 48 compression fractures and 21 fracture dislocations, 8 flexion distraction fractures and 6 flexion rotation injuries. Ninety-three patients underwent anterior cord decompression and strut grafting followed by posterior CD instrumentation and posterolateral fusion. Fifty-seven patients had posterior CD instrumentation and fusion alone. No neurological deterioration after the procedure was observed, 33 patients improved neurologically. Hospital stay ranged between 7 and 60 days (mean 20 days). 114 patients had a minimum follow up of 6 months (range 6-52 months). The mean follow up was 17.7 months. At final follow up 77.8% of the patients had returned to work and 84.2% of the patients were almost painfree. The mean loss of correction in the sagittal plane was 6.2 degrees (range: 0 and 42 degrees) at final follow up. As technical complications there were four hook cut outs (2.6%) of which two underwent reosteosynthesis and two did not effect the clinical or radiographic result. The high stability of the device provides a decreased risk of neurological deterioration, a decreased risk of posttraumatic kyphosis and early rehabilitation. PMID- 8342346 TI - [Bilateral rupture of the quadriceps tendon--case report and review of the literature]. AB - We report a very rare case of bilateral simultaneous rupture of the quadriceps tendons in a 64-year-old patient following a minor trauma. The reconstruction of the ruptured tendons was achieved by intertwined PDS-sutures which were supportively fixed in the patellae. After wound healing, the patient was mobilized in his two casts which were applied for 6 weeks. After the period of one year, a satisfactory result could be seen. We report the etiology, pathogenesis, diagnosis, therapy and postoperative treatment which are described in the literature. PMID- 8342347 TI - [The incidence of abortions of viable pregnancies in the first trimester]. AB - The spontaneous abortion rate in singleton pregnancies with sonographically proven heart activity between 5 and 13 weeks was analysed. Up to 15 weeks 8.6% of 395 patients miscarried. The abortion rate was higher in pregnancies with a gestational age < 9 weeks (12.5%), a maternal age > or = 35 years (15.5%) and vaginal bleeding (16.3%). The correlation of the abortion rate with these factors has to be taken into account when the prognosis of an individual gestation or the risk of invasive procedures is determined. PMID- 8342348 TI - [Cellular lymphatic tissue of the endometrium and uterine tube]. AB - The presence of T-lymphocyte subsets in human endometrium and tubal mucosa in correlation to the menstrual cycle was investigated by the immunoperoxidase technique. The main cell populations were the pan T-cells (CD 3) and T-suppressor cells (CD 8). The T-helper cells (CD 4) and the B-lymphocytes (CD 22) were sparsely distributed. Significant differences between the phases of menstrual cycle could not be observed. PMID- 8342349 TI - [Echinococcosis in pregnancy. A rare differential diagnosis in cystic intra abdominal tumors in pregnancy]. AB - Pregnancy and intraabdominal masses rarely cointcidate. Therapeutical consequences are associated with possible complications such as intraabdominal pain, torquation of cystic tumors, rupture of cystic masses and pelvic inflammation. In less than 5% of the cases a malignant process during pregnancy can be expected. Prior to therapy of intraabdominal masses patients from typical endemic areas ought to be checked up for parasitic infections such as cystic echinococcosis treated specifically. Based on the following case report we present the epidemiology, diagnosis and therapy of cystics echinococcosis in pregnancy. PMID- 8342350 TI - [Femoral nerve paralysis after vaginal hysterectomy and its forensic importance]. AB - Paresis of the femoral nerve following vaginal hysterectomy is a rare event, only 21 cases have been reported in the literature. This lesion is caused by pressure of the femoral nerve through the ligamentum inguinale during extreme flection and abduction of the thigh when vaginal surgery is done in lithotomy position. To avoid this femoral nerve lesion during vaginal hysterectomy the inclination angle between thigh and body should not be smaller than 45 degrees and the abduction angle should not exceed 45 degrees in relation to a vertical midline. The correct positioning of the patients has to be checked and documented by the gynecologist performing the operation. The operating gynecologist is responsible for injuries and damages by incorrect positioning of the patient. PMID- 8342352 TI - [Congress of the Netherlands Society of Obstetrics and Gynecology, Amsterdam, 20 21 November 1992]. PMID- 8342351 TI - [Simultaneous occurrence of a squamous epithelial and adenocarcinoma of the endometrium]. PMID- 8342353 TI - [Our gynecologic heritage. Robert von Olshausen (1835-1915), pioneer in surgical gynecology. 5th contribution on the history of the Berlin Society of Obstetrics and Gynecology]. AB - Robert von Olshausen was an outstanding German gynecologist at the turn of the century and a pioneer of operative gynaecology. His fields of excellency were ovarotomy, the problems of asepsis, carcinoma therapy and the development of obstetrics in general. Under his chairmansship, the Berlin Department of Obstetrics and Gynecology (Universitats-Frauenklinik) became the leading Clinic in Germany. For many years Olshausen was the chairman of the Berlin Society of Obstetrics and Gynecology, since 1894 as honorary chairman. The present paper is a biography of Robert von Olshausen, showing his importance for the development of the modern gynaecology in Berlin and Germany. PMID- 8342354 TI - [Cardiotocography practice case no. 24]. PMID- 8342355 TI - Induction of serotonin-S2 receptor blockade during early or late stage of acute respiratory distress syndrome in double-muscled calves: a comparative study. AB - Ninety-four Belgian White and Blue double-muscled calves were involved in this study which aimed to compare the efficacy of a serotonin-S2 receptor blockade at two different stages of an acute respiratory distress syndrome (ARDS), i.e. at the occurrence of first clinical signs or when another anti-inflammatory compound was clinically shown to be ineffective. Metrenperone, a 5-hydroxytryptamine (5 HT2) blocker, was injected (intramuscularly, 5 times, at 12 hourly intervals, dose rate: 0.1 mg/kg) to (1) 58 calves referred to our laboratory after a treatment (group I) which lasted from 3 to 5 days and which did not improve the clinical status of the animals and (2) 36 calves investigated as soon as first clinical signs occurred (group II). Following the severity of the ARDS, the animals from group I needed to be classified into 2 groups: group IA (moderate ARDS - n = 45) and group IB (severe ARDS - n = 13). For animals in group I, the antibacterial compound previously used was maintained and administered during 4 more days whilst the previous anti-inflammatory drug was suppressed and replaced by metrenperone administered as mentioned above. In group II, each animal was treated with ceftiofur sodium as an antibacterial agent. A clinical score and a breathing score were calculated at each step of the investigation period, i.e. before (T0) and 1 hour (T1) after the first treatment, during the interval 12H 48H (T2) which followed this treatment and 168 H (T3) after this treatment. Four clinical parameters were also taken into account separately: rectal and cutaneous temperatures, respiratory and heart rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342356 TI - Body weight loss during lactation in relation to energy and protein metabolism in standard-fed primiparous sows. AB - After 5 weeks of lactation 14 standard-fed primiparous sows were divided into a low weight-loss group (L-gr, loss < 25 kg, n = 7) and a high weight-loss group (H gr, loss > or = 25 kg, n = 7). Body weights of the sows and their litters were recorded on days 2, 7, 14, 21, 28 and 35 of lactation. Blood samples were collected before the morning feeding on each weighing day. Samples were analysed to determine concentrations of insulin, glucagon, glucose, triglycerides, non esterified fatty acids (NEFA), urea and creatinine. The H-gr sows lost weight throughout lactation, whereas the L-gr sows gained weight during the last week. Weight loss was higher in the H-gr than in the L-gr during weeks 2, 3 and 5 of lactation. Litter size and litter weight gain were higher in the H-gr than in the L-gr. Significant changes in levels of insulin, glucagon, glucose, triglycerides and creatinine were observed over lactation. No significant differences in concentrations of any of the parameters were found between the two groups, except for insulin and cholesterol which were higher in the L-gr. Catabolism of adipose tissue and muscle protein was observed in both groups during the first week of lactation. This catabolic state was more pronounced and tended to be prolonged in the H-gr. Concentrations of all parameters seemed to be stable in both groups during the last two weeks of lactation. PMID- 8342357 TI - Effect of storage of blood on the osmotic fragility of mammalian erythrocytes. AB - The osmotic fragility of mammalian erythrocytes during blood storage was determined. Significant changes were observed in the fragility of goat, cattle, pig, mouse, rat and rabbit erythrocytes but not in sheep erythrocytes during the storage of blood for 24 hours at 10 degrees C. PMID- 8342358 TI - Stress induced gizzard erosion in chicks. I. Gross and histopathological findings. AB - A model of stress induced gizzard erosions is described. Three day old chickens were deprived of food for 24 h, and after that they were immersed in tap water (17 degrees C) for five seconds. Group A was sacrificed immediately before being subjected to stress, group B one hour, group C two hours and group D three hours after water immersion stress. Each group consisted of 10 animals. Gizzard lesions in group A were very mild and the main feature was discoloration of the gizzard lining. In groups B, C, and D the lesions were more severe and they were characterised by gizzard erosions, ulcerations and hemorrhages especially pronounced in group D. This model produced lesions in all stressed animals. PMID- 8342359 TI - Combining two independent indirect methods as a new possibility for screening the illegal use of growth promotants. AB - In this study the possibilities of combined indirect screening methods for the growth promotants clenbuterol and estradiol-17 beta benzoate and the combination of both these agents were investigated. Three groups of 5 male goat kids (two months of age) were treated for 4 weeks; clenbuterol per os, 10 micrograms/day/kg body weight via milkreplacer twice a day; 2 mg estradiol-17 beta benzoate weekly per i.m. injection; combined clenbuterol per os+estradiol-17 beta benzoate per injection. Five animals were not treated and served as controls. Nuclear Magnetic Resonance (NMR) was used as an initial tool to monitor the urine composition. The analysis of NMR spectra showed, that most treated animals had increased L lactate/creatine ratios (L/C-ratio) in their urine, compared to control animals. For screening, L-lactate/creatine ratios could be determined directly in urine- in a simple, quick and inexpensive manner--by using enzymatic methods and an autoanalyzer. Histologically clenbuterol induced degenerative changes in the urethral and glandular epithelium of the prostate. Changes consisted of vacuolization of the epithelium and necrosis with nuclear pyknosis and fragmentation. Estradiol-17 beta benzoate induced metaplastic changes in the glandular tissue of the goat prostate. In combination with estradiol-17 beta benzoate, characteristics of both agents could be observed. The histological methods and observed effects can be used directly for screening. The combination of independent histological and L/C-ratio methods looks very promising with respect to screening of growth promotants. Since in both cases effects of growth promotants are detected, it may be expected that this approach is not limited to goats or clenbuterol and estradiol alone. PMID- 8342360 TI - Cation-induced aggregation of cat Tamm-Horsfall glycoprotein and its possible role in feline urolithiasis. AB - The in vitro cation-induced aggregation properties of cat Tamm-Horsfall protein (cTHP), a urinary glycoprotein, were examined and related to the potential role of cTHP in feline urolithiasis. The aggregation assay involved adding either CaCl2, MgCl2, or NaCl to solutions containing purified cTHP, and then separating the aggregated cTHP by centrifugation. The concentration of cTHP remaining in the supernatant was quantified using a previously developed enzyme-linked immunosorbent assay (ELISA). The effect that buffer pH, cTHP concentration, and urea concentration had on cTHP aggregation also were examined. Of the three salts, CaCl2 consistently was most efficient at precipitating cTHP, while MgCl2 was slightly less efficient. At least ten times more NaCl than CaCl2 or MgCl2 was required for comparable cTHP aggregation. As the pH decreased, increasing concentrations of the salts were required to aggregate cTHP. Increased amounts of CaCl2 and MgCl2 also were required to aggregate cTHP when the urea concentration was increased. As cTHP concentration increased within the physiological range, lower concentrations of CaCl2 and MgCl2 were required to precipitate 50% of the cTHP. Several aspects of the in vitro aggregation properties of cTHP correlate closely with previously identified risk factors for feline urolithiasis, strengthening the theory that cTHP aggregation may be important in this disease. PMID- 8342361 TI - [M-mode echocardiography in dressage horses, class S jumping horses and untrained horses]. AB - Heart structures of 45 warmblooded horses were measured by M-mode echocardiography. The current training level of 15 dressage horses (group I) and 15 show-jumping horses (group II) was category "S". In the third group were 15 untrained horses. Four standardized transducer positions were determined for the m-mode echobeam, calibrated according to the two-dimensional real time technique. End systolic and end diastolic diameters of left ventricle, right ventricle, aortic root, interventricular septum and left ventricular wall, as well as motion pattern of heart wall, mitral valve and aortic valve of all horses were measured. The dressage horses showed a significant thickening of interventricular septum and left-ventricular wall compared with the show-jumping horses and the untrained horses. The end diastolic left ventricle diameter of the show-jumping horses was significantly larger than in the other groups. Compared to the untrained horses the show-jumping horses showed a significantly larger end systolic left ventricular wall diameter measured at the level of papillary muscle. It can be concluded, that an increase in heart mass in category "S" sport horses is attributed to their level of training. PMID- 8342362 TI - Simultaneous genotyping of sex and kappa-casein of bovine in vitro fertilized embryos by the PCR technique. AB - Sex and the kappa-casein genotype of in vitro produced cattle demiembryos was identified by simultaneous PCR-genotyping using polymorphic sites in ZFY/ZFX and kappa-casein genes. We obtained PCR products of 530 bp (kappa-casein) and of 445/447 bp (sex). Sex and the two kappa-casein alleles could be identified after digestion of the PCR products with Pstl and simultaneous separation of the restriction fragments on one step, allowing a rapid and efficient analyses of embryos. PMID- 8342363 TI - Effect of various dietary selenium (Se) intakes on tissue Se levels and glutathione peroxidase activities in lambs. AB - Experiments were conducted to examine selenium (Se) metabolism in tissues of lambs following Se supplementation at varying doses. For three months four groups of lambs were fed either a basal diet (group A) containing 0.082 mg Se per kg dry matter (ppm) or the same diet plus mineral mixture with Se (as selenite) so that the total diet contained 0.25, 0.41 and 0.58 ppm Se (groups B, C and D, respectively). After three months six lambs of each group were slaughtered and tissues were removed for Se level and GSH-Px activity determinations. Among the tissues of lambs fed the basal diet the highest Se concentration was found in the kidney (1.32 micrograms/g wet weight), and the lowest in the skeletal muscle (0.030 micrograms/g wet weight). In the liver, heart, lung and spleen Se concentrations were almost at the same level and varied in the range of 0.14 to 0.18 micrograms/g wet weight tissue. No increase in Se concentration was found in the kidneys of Se-supplemented animals. Se concentration in the liver and lung increased linearly with the Se level in the diet. In the spleen, heart and skeletal muscle the highest Se concentrations were found in lambs fed 0.41 ppm Se. Tissue GSH-Px activities (calculated on the per g protein basis) increased significantly in Se-treated animals. In the tissues of lambs fed 0.25 ppm Se the enzyme activities were higher in a range of 1.8 to 3.5 as compared to the group fed the basal diet. Higher doses of dietary Se had much smaller effect on the tissues GSH-Px activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342364 TI - Control of infections with Mycoplasma hyopneumoniae in swine herds by disrupting the chain of infection, disinfection of buildings and strategic medical treatment. AB - A program with the aim to eliminate infections with Mycoplasma hyopneumoniae was applied in 4 herds selling breeding pigs. A "fast" (1 month) variant of the program was applied in one herd selling young gilts (30 kg body weight) and in one herd selling adult breeding stock, and a "slow" (> or = 3.5 months) variant was applied in two corresponding herds. In both variants, the spread of infections was prevented by isolating the breeding stock. These animals were treated with tiamulin before being reintroduced to the original, but emptied and disinfected units. Further, the rearing of pigs born before and after initiating the program was separated. In both herds selling young gilts, no antibodies to Mycoplasma hyopneumoniae were detected in sera collected for at least 40 months after finishing the program. In the herds selling adult breeding pigs, elimination of infections with Mycoplasma hyopneumoniae was only achieved by the "fast" variant, while the infections still were present in the breeding herd using the "slow" variant of the program. The failure of the program in the latter herd was probably due to turbulent air flows between ventilation systems of units situated close to each other and simultaneously housing uninfected and infected pigs. PMID- 8342365 TI - Dose-dependent pathophysiological changes in cattle experimentally infected Dictyocaulus viviparus. AB - In two trials five calves were each experimentally infected on three consecutive days with a total number of either 30 Dictyocaulus viviparus larvae per kg body weight (trial A) or 3 larvae/kg body weight (trial B). Five calves served as non infected controls. Infected cattle in trial A developed severe clinical signs of dictyocaulosis and one calf died 37 days post infection (p.i.), whereas all cattle in trial B remained clinically healthy. Weight gains in both trials were not statistically different. Haemoglobin concentrations, packed cell volume (PCV), number of erythrocytes and leucocytes, blood pH and albumin concentrations were in the physiological range in all groups. Infected cattle in trial A showed increases in respiratory rates, body temperature, serum protein concentrations, and blood eosinophil counts and decreases in oxygen partial pressure. Infected cattle in trial B showed increased blood eosinophil counts. Antibody formation in infected cattle of both trials showed a similar pattern. Excretion of larvae from infected cattle reflected the different infection doses. Microbiological examinations showed an increase of facultatively pathogenic bacteria in the lung fluid. PMID- 8342366 TI - Experimental cerebrospinal elaphostrongylosis (Elaphostrongylus rangiferi) in sheep. AB - Seven lambs were inoculated with 150-3,000 infective larvae of Elaphostrongylus rangiferi and subsequently killed for autopsy. From one week post inoculation (p.i.), a marked eosinophilia was found, and one of the lambs showed signs of coughing, increased respiratory frequency and elevated body temperature. Pruritus was observed in three lambs during the period 5-10 weeks p.i. Gross and microscopic lesions were found in the liver, lungs, myocardium, kidneys, spinal nerve roots and in the central nervous system (CNS). The lesions resembled those previously reported in experimentally infected goat kids. The migratory route of the infective larvae seemed to be haematogenous. Developing nematodes were sectioned in the CNS of a lamb killed at day 30 p.i. The nematodes found in the brain of this lamb were significantly thicker than those observed in the spinal cord. Intact nematodes were not detected in the remaining lambs which were all killed 149-151 days p.i. None of the experimental lambs shed E. rangiferi first stage larvae in the faeces. These findings indicate that E. rangiferi gradually dies out in sheep and will not complete its life cycle in this animal species. PMID- 8342368 TI - The development of pulmonary lesions associated with dead adult D. immitis in naive dogs. AB - The sequential response of the lung to the death of adult D. immitis has not been reported. To determine the time sequence and severity of pulmonary lesions following the death of D. immitis, light microscopy was used to follow 36 dogs, detailing the respective lesions 1-35 days after insertion of dead D. immitis or of control polyvinyl chloride threads. Results showed that dogs exposed to dead filariae developed more severe pulmonary arterial disease than did those exposed to inert threads. Severe pulmonary lesions occurred at 5-9 days post insertion with the right caudal lobes being the most affected, both macro and microscopically. These findings suggest that this was a suitable model for the study of this parasite-host interaction and that 5-9 days following insertion of dead D. immitis was the most intensive period of host reactivity. PMID- 8342367 TI - Research on the presence of porcine enterovirus serotype 1 in north-eastern Italy. AB - The liquid-phase blocking sandwich ELISA, already developed for foot-and-mouth disease and swine vesicular disease serology, has been employed in pig sera for the antibody detection against porcine enterovirus serotype 1. ELISA-titers correlate positively with virus neutralization and their distribution show a high prevalence among the sampled pigs. The serological findings are confirmed by the isolation of a field strain of porcine enterovirus belonging to the serotype 1. PMID- 8342369 TI - Staphylococcus intermedius: current knowledge on a pathogen of veterinary importance. AB - It has been 16 years since the identification of S. intermedius as a new species. Numerous investigations using cell wall and DNA analytic methods have now clearly demonstrated significant differences to warrant the creation of this new species. However, studies investigating virulence factors associated with S. intermedius have not uncovered evidence that differentiates virulent from non-virulent isolates. Therefore, at the present time, it is difficult for veterinary clinicians and microbiologists to determine the clinical significance of many S. intermedius isolates. Host-bacterial interactions and the hosts' immune status appear to be the factors most crucial in determining the outcome of infections, not the virulence of the organism. Continued research in the virulence factor field will hopefully lead to a better understanding on how we can differentiate virulent from nonvirulent isolates of S. intermedius. PMID- 8342370 TI - Antigenicity of Dermatophilus congolensis hemolysin. AB - The separated cell-free form of hemolytic exosubstance was obtained from five strains of Dermatophilus congolensis. Three strains produced exosubstance with high activity, two strains produced exosubstance with lower intensity of activity. The separated forms exhibited the same hemolytic interactions as the native forms produced by growing strains, namely the antagonism with staphylococcal beta hemolysin and the synergism with staphylococcal delta hemolysin, streptococcal CAMP factor and rhodococcal equi factor. Rabbit sera obtained after intravenous or intraperitoneal application of the separated forms contained precipitation and neutralization antibodies. Cross tests of precipitation and neutralization proved antigen identity of hemolysins of different D. congolensis, strains which makes the serodiagnostics of this species possible. PMID- 8342371 TI - Intestinal carriage of Clostridium difficile in neonate dogs. AB - A total of 70 puppies and their dams, distributed in 14 litters, were submitted to weekly fecal examinations for C. difficile during the first 10 weeks after birth. During the study, 94.3% of the puppies and 42.9% of the dams harboured C. difficile at least once in their feces. We calculated that 58% of the puppies carried toxigenic C. difficile at least once during the survey. In the puppies, C. difficile carriage rates ranging from 3.1% to 67.1% were observed at different moments of the observation period. In comparison, C. difficile carriage rate was 1.4% in a control group of healthy dogs more than 3 months old. Discrepancies in the toxigenic phenotype of the C. difficile strains isolated in the same litter showed that the neonate dogs were transiently infected with different strains, and that the dam is often not the source of infection with C. difficile. We could not demonstrate any pathogenicity of C. difficile for neonate dogs. PMID- 8342372 TI - [Basic indicators of cellular immunity in patients with chronic staphylococcal osteomyelitis]. AB - The objective of the presented work is to compare the state of the immune system in patients with chronic osteomyelitis with a group of the healthy population. The authors followed up on a long-term basis a group of 24 patients with chronic osteomyelitis of staphylococcal origin; they completed immunological examinations comprising cellular and humoral immunity (in particular assessment of T lymphocytes and their sub-populations by means of monoclonal antibodies, examination of phagocytic capacities of blood elements, assessment of selected plasma protein and immunoglobulin levels). Comparison of results of these examinations in patients with chronic osteomyelitis and the healthy population proved statistically very significant differences in particular in the number of T-lymphocytes (reduction of T-lymphocytes CD 4+, i.e. helpers, immunity stimulating cells and reduction of the ratio of immunity promoting lymphocytes and immunity inhibiting lymphocytes). The authors found also significant differences in the levels of plasma proteins and immunoglobulins. PMID- 8342373 TI - [The closed method of intramedullary fixation of forearm fractures]. AB - The authors demonstrate a group of 27 patients subjected to intramedullary osteosynthesis of the forearm by means of Kirschner wires, using closed surgery. They prefer the described method in patients suffering from multiple injuries who have devastated soft parts of the forearm and in unstable fractures in children. The authors draw attention to the fact that they have achieved very good results by the simple surgical method they described. PMID- 8342374 TI - [Personal experience with treatment of Pipkin fractures of the femoral head]. AB - In the introduction the authors analyze the classification and incidence of fractures of the Pipkin type. This is a rare injury which develops as a rule in 10% of posterior type dislocations during motor car crashes. The authors present a theoretical review of all therapeutic possibilities in specific types of fractures. The group comprises 17 patients during a follow-up period of 16 years, mean age of the patients 39.6 years. In 82% the cause of the injury was a car accident. Type IV fractures were most frequent, consistent with data in the literature only one type III fracture was recorded. Sixteen patients were operated incl. three operated after a long time interval following the injury. The authors evaluate nine patients who were at least one year past the injury. The average period which had elapsed since the injury was 7.3 years. From the evaluation patients were eliminated who had primary or secondary prostheses of the hip joint. According to the score based on modified evaluation of Thompson, Epstein and Motta 44 excellent and very good results were achieved, one poor result. Two patients were granted full invalid pensions. In the discussion the authors compare their views and results with those reported in the literature. In the conclusion the authors state that treatment of these fractures should be provided at highly specialized departments. PMID- 8342375 TI - [Possibilities of using the sartorius muscle in the treatment of chronic osteoarticular infections]. AB - In a group of 17 patients with chronic osteoarticular infection for filling of the chronic cavity the sartorius muscle was used. In eight instances chronic osteomyelitis of the distal femur was involved, in nine instances by means of the sartorius muscle the acetabulum was filled (after removal of an infected total endoprosthesis or after resection of the hip joint on account of purulent coxitis). In the first group the authors recorded 75% satisfactory results and therefore they recommend to use the sartorius muscle for filling chronic osteomyelitic cavities in the distal part of the femur with a fistula on the inner side of the thigh. In the second group of patients, where the sartorius muscle was used to fill the acetabulum, poor results were recorded in 55.5%. This is obviously associated with the blood supply of the muscle used, which does not permit such an extensive mobilization and rotation of the muscle without jeopardizing its nutrition. Therefore the authors do not recommend the use of the sartorius muscle for filling the acetabulum and propose other muscle flaps which gave preliminary, satisfactory results. PMID- 8342376 TI - [The role of pharmacology in the comprehensive prophylaxis of post-traumatic fat embolism]. AB - Immediate high-standard provisions implemented as soon as possible after serious injuries with the aim to prevent the development of shock or to treat incipient and developing shock is one of the most important aspects of prophylaxis of the syndrome of traumatic fat embolism (FE). An important place is held by the rostoration of normal microcirculation, replacement of blood losses and the control of hypoxia, in particular by artificial pulmonary ventilation. A high caloric intake both by the parenteral and enteral route has among others the objective to prevent excessive development of lipolysis. Surgical operations with the exception of urgent ones which must not be delayed should be postponed till complete regression of clinical manifestations of traumatic shock. The group of comprehensive provisions comprises pharmacological provisions against traumatic shock and pharmacological participation in the prophylaxis of the FE syndrome: Lipostabil; Trasylol; heparin and other anticoagulants in small doses; hydrocortisone; dextrans, CaCl2 and possibly other effective substances or drugs in rational individually recommended doses and expedient combinations. PMID- 8342377 TI - [Amputation and prosthesis design in severe congenital defects of the lower extremity (case reports)]. AB - The author presents an account of three patients with severe congenital defects of the lower extremities who relied on a long-term basis on complex prosthetic appliances. In the mentioned patients the author amputated part of the malformed extremity in such a way as to preserve the "plantar" stump and it was thus possible, when solving the technical aspects of the appliance, to improve also the cosmetic covering of the defect. PMID- 8342378 TI - [Leg lengthening using callotasis. I. History of lengthening of extremities and surgical technics]. AB - In the first part of the article divided into two sections the authors describe the history of approaches to limb length discrepancy and they compare several methods and discuss their advantages and disadvantages. The surgical method proper used at the clinic is described incl. preoperative preparation and deliberations as used at the clinic up to the procedure used for removing the fixator after completion of the lengthening of long bones. The operation proper is described in detail from application of the apparatus to performance of osteotomy. The lengthening process is also described. PMID- 8342379 TI - [Factors affecting the development of para-articular ossification in total hip replacement]. AB - The authors evaluated the prevalence of paraarticular ossifications in three groups of patients after a minimum interval of one year following the administration of a total prosthesis. For evaluation they used Brooker's classification. The first group comprised 40 patients who during the first six weeks after administration of a cemented prosthesis of the hip joint took 75 mg of Indomethacin per day in three doses. The second control group comprised 50 patients, i.e. 61 operated hip joints (11 bilateral prostheses) to whom Indomethacin was not administered during the postoperative period, nor any other antiphlogistic preparations. The third group comprised 40 patients to whom a non cemented prosthesis of the hip joint was implanted and who did not use any antiphlogistic preparations after operation. In the first group, i.e. patients after total endoprostheses of the hip joint with preventive administration of Indomethacin, ectopic ossifications were recorded in 32.5% of the operated patients. In the second group, i.e. without preventive Indomethacin administration, ectopic ossifications of various grades were recorded in 51%. In patients with non-cemented prostheses of the hip joint the prevalence of ectopic ossifications was only 18%. The authors selected from the control group a sub group with bilateral prostheses of the hip joint where an ectopic bone was found. This sub-group comprised 9 operated patients and bilateral ectopic ossifications developed only in 33.3%. From the results ensues that Indomethacin administration is an expedient prevention of development of paraarticular ossifications. Marked reduction of development of ectopic bone formation occurs when bone cement is not used as a fixation medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342380 TI - [Personal experience with the use of the Herbert screw in orthopedics and traumatology]. AB - The authors present in the submitted paper their initial experience as well as theoretical possibilities of using Herbert's screw. This is a relatively new type of implant developed originally for stable compressive osteosynthesis of small bones. This screw is made from a titanium alloy in sizes of 16-32 mm and is based on the principle of traction screws. It has, however, compared with the latter some advantages and thus makes a reduction of the period of postoperative fixation possible. It is supplied along with the insertion instruments which facilitate peroperative reposition and retention of fragments for easier insertion of the screw. In the authors' department this screw was used in 1988 1991 for osteosynthesis in 18 patients incl. 12 with fractures of the navicular bone, head of the radius, the patella, Bennett's fracture, osteochondral fractures of the femoral condyle and it was also used for osteosynthesis of scapholunatal desis and desis of the interphalangeal articulations of the hand. In the authors' so far not very numerous group Herbert's screw proved useful- only in one patient the X-ray and clinical finding was not satisfactory and called for further surgical operation. It is, of course, essential to respect the surgical principles for its application, in particular in fractures of the navicular bone. The implant is an advance in the treatment of selected recent injuries as well as their late sequelae. PMID- 8342381 TI - Secondary intramedullary nailing of complicated fractures of lower extremities. AB - Between 1984 and 1991, 16 patients with 23 fractures of the lower extremities were treated with external skeletal fixation and subsequent intramedullary nailing. There were 7 closed fractures, 1 closed fracture with vascular injury, 2 Grade I, 3 Grade II and 10 Grade III injuries, sansistiny of 5 Grade IIIA, 2 Grade IIIB and 3 Grade IIIC fractures. The fractures were maintained in external fixation for an average of 14 days (range 4 to 32 days) after which the fixateur was removed and an intramedullary nail placed during the same procedure in all cases. Two of the twenty-three fractures, 9%, subsequently developed deep infections involving the intramedullary canal, both of which resolved with antibiotics while retaining the nail. Thus we were able to place intramedullary fixation in these difficult and often contaminated injuries in less than one month with a relatively low incidence of complications. PMID- 8342382 TI - [Initial experience with peroperative autotransfusion in spinal surgery]. AB - The authors describe combinations of anaesthesiological methods which enabled them during extensive spondylosurgical operations in 66 patients to reduce the consumption of homologous blood during operation to 90 ml, on the first day after operation to 300 ml and on the second day after operation to 120 ml. In six patients they used preoperative collection of the patient's own blood, in 45 patients acute normovolaemic haemodilution, in all patients controlled hypotension with sodium nitroprusside to a mean arterial pressure of 8-9 kPa and peroperative collection of blood by means of an autotransfusion apparatus Dideco Stat with a standard programme and yield higher than 50%. During and after peroperative collection they did not record any complications. Lower haemoglobin and haematocrit values and a reduced number of erythrocytes, lower than the lower normal range, during and after operation did not threaten the postoperative course in these patients. The authors draw, however, attention to the rise of the number of leucocytes immediately after operation to 19.7 x 10(9). 1(-1) which is due to their shift into the final product. Solution of this phenomenon which can produce ARDS is according to the authors the use of a programme different from the standard one. PMID- 8342383 TI - [Arthroscopic meniscopexy]. AB - The author analyses indications and therapeutic possibilities of arthroscopic meniscopexy and presents his own results assembled at the First Orthopaedic Clinic of the Masaryk University in Brno. He describes the surgical technique used, i.e. OUTSIDE-IN, in treatment of recent paracapsular ruptures of the meniscus, postoperative fixation and the rehabilitation programme. The author discusses also the necessity of a rigid plaster fixation and advocates fixation of the knee joint by a bandage as proposed by R. Jones with elimination of burdening for a period of eight weeks. PMID- 8342384 TI - Non-conventional growth hormone treatment in short children. AB - Despite the fact that GH has been available in sufficient amounts to allow treatment in non-conventional indications during childhood, results on final height are not available or are available in only very small groups of patients. Much has to be done to answer the question of how to optimize GH treatment, with respect not only to final height, but also to normal psychosocial development. PMID- 8342385 TI - Growth hormone and bone metabolism. AB - GH is a potent anabolic hormone for bone and calcium metabolism, not only via direct effects but also mediated through other systems. The individual effects on bone metabolism are summarized in Table 1. Some of the signs (low BMD and low serum osteocalcin) and symptoms (increased prevalence of vertebral fractures) seen in patients with GHD may be due to the lack of GH itself, others may be due to secondary hormone deficiencies or changes in body composition induced by GHD. GH treatment can reverse changes of calcium metabolism. Whether it is able to increase bone mass still needs to be determined in larger and longer studies. Some patients with established osteoporosis and vertebral fractures seem to suffer from GHD. Treatment of osteoporosis with GH has not previously been successful, but studies with more patients over several years to investigate the effects of GH treatment on vertebral fracture rates are lacking. As GH seems to reverse some signs of old age, such as muscle weakness and reduced exercise capacity, it is possible to speculate that GH could prevent the occurrence of hip fractures in elderly people. PMID- 8342386 TI - Effect of growth hormone on muscle and protein in critically ill patients. AB - In summary, the effects of protein metabolism of the provision of additional GH are well documented in critically ill patients. Nitrogen balance improves as urea production is diminished. The crucial question is whether this lowers the availability of glutamine for cells dependent on it in critical illness. In parallel, muscle protein synthesis is stimulated by GH and the free glutamine content of muscle is maintained in situations when a depletion of muscle glutamine is otherwise seen. Another consistent finding in most clinical studies is the pronounced interindividual variability in the response to GH. So far, no marker has been identified to predict an individual patient's sensitivity to GH, but the identification of individuals who are likely to benefit from GH treatment during critical illness should be a priority in future clinical research on GH. PMID- 8342387 TI - The consequences of growth hormone deficiency in adults. PMID- 8342388 TI - Effects of growth hormone on reproduction. PMID- 8342389 TI - Growth hormone and low-density lipoproteins. PMID- 8342390 TI - Evaluation of different methods of determining body composition, with special reference to growth hormone-related disorders. PMID- 8342391 TI - Preliminary report on the development of a disease-specific instrument for assessing quality of life of adults with growth hormone deficiency. AB - It is notable that many of the feelings described by the people in the sample are similar to those experienced at times by people who do not suffer from GHD, that is, lapses of memory, feeling drained of energy, loss of temper, loss of motivation, difficulty in concentrating, forgetfulness and having a tendency to gain weight. Adults with GHD, however, appear to suffer these problems more frequently and to a more extreme degree than other people. It is clear that the range of problems that afflict people with GHD is great, and that the repercussions affect virtually all aspects of their lives. The results from these interviews will form the basis of a measure designed specifically to assess the quality of life of patients with GHD, and to determine the changes in quality of life after treatment with GH. PMID- 8342392 TI - Preliminary study of the effects of growth hormone substitution therapy on bone mineral density and serum osteocalcin levels in adults with growth hormone deficiency. AB - In order to evaluate the consequences of pituitary insufficiency on bone mineral status, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 33 patients (aged 22-65 years) with pituitary insufficiency. BMD of the lumbar spine and femoral neck was decreased. Twenty of the patients were randomized to receive either recombinant human growth hormone (GH), 0.25 IU/kg/week for 6 months (0.125 IU/kg/week during the first month), or placebo. Serum osteocalcin levels increased significantly during GH administration. In the GH-treated group, there was no change in lumbar spine BMD and a small but significant decrease in femoral neck BMD (p < 0.05) after 6 months. Treatment periods longer than 6 months are needed to evaluate the potential beneficial effect of GH on BMD. This is in accordance with our previous findings of an increase in forearm BMD after 12 months of GH substitution therapy. PMID- 8342393 TI - Protein metabolism in growth hormone deficiency, and effects of growth hormone replacement therapy. AB - The effects of growth hormone (GH) treatment on protein metabolism were studied in adults with GH deficiency (GHD). A double-blind, placebo-controlled trial of recombinant human GH, 0.018 IU/kg/day for 1 month followed by 0.036 IU/kg/day for 1 month, was performed with isotopic whole-body protein turnover studies at 0 and 2 months. In all, 18 adults with GHD (9 men, 9 women; mean age, 46.6 years; range, 30-56 years) were studied. Whole-body isotopic leucine turnover using L-[1 13C]leucine was assessed by measuring leucine Ra (a measure of protein degradation), non-oxidative leucine Rd (a measure of protein synthesis) and leucine oxidation rate. Lean body mass and circulating insulin-like growth factor I were significantly (p < 0.02) increased at 2 months in the GH-treated group, but not in the placebo group. There was no change in leucine Ra in either the placebo or GH-treated groups at 2 months. Leucine oxidation decreased (p < 0.01) and non-oxidative leucine Rd increased (p < 0.02) in the GH-treated group at 2 months. There was no significant change in either leucine oxidation or non oxidative leucine Rd in the placebo group at 2 months. These results indicate that the increase in lean body mass resulting from GH treatment in adults with GHD is due to an increase in protein synthesis. PMID- 8342394 TI - Economic evaluation of health care technologies. AB - Despite two decades of developments, economic evaluation of medical therapies is still in its infancy. The first decade was mainly a search for a relevant methodology, a period when it was important to establish that new medical technologies carried not only costs but also economic benefits. The costs-of illness methodology was the most convenient to use and served well to show that new medical technology produced economic benefits. It was obvious, however, that the method had its limitations, particularly in health care systems devoting more and more resources to the elderly, not an economically active part of the population. For other people also, health per se is more important than health as a human capital that improves work capacity. The studies undertaken in the 1970s were mainly based on epidemiological data and undertaken at arms' length from clinical activities in hospitals and in general practice. At the beginning of the 1980s, it became clear that in order to become more relevant, economic evaluations have to be linked much more closely to the clinical evaluation of new technologies. Clinicians and economists have to work together to produce good and relevant studies. The beginning of the 1980s saw such an increase in collaboration between economists and clinicians, and some important studies were undertaken. These studies were mainly concerned with calculating costs for different clinical actions and determining cost-effectiveness using, for example, number of life-years gained. During the last 5 years, interest has been focused on the problems and opportunities of including quality of life and utility estimates in economic evaluations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342395 TI - Long-term consequences of growth hormone deficiency acquired in childhood. PMID- 8342396 TI - Workshop report: protein metabolism and muscles. The effects of growth hormone and growth hormone deficiency. PMID- 8342397 TI - [Current contribution of molecular biology in the diagnosis of hepatitis B]. AB - Recent advances in molecular biology had led to a better understanding of the pathology of hepatitis B virus. The polymerase chain reaction technique has shown that the genome of hepatitis B virus is highly variable. Mutations in the pre core region are associated with HBe Ag negative chronic hepatitis and fulminant hepatitis B; moreover, rare cases of hepatitis due to HBV with mutations within the S gene have been reported in HBV-vaccinated patients. The aim of this paper is to assess the clinical, serological and therapeutic features of hepatitis B variants. PMID- 8342398 TI - Georges Brohee Prize. Oestrogen-progesterone, a new therapy of bleeding gastrointestinal vascular malformations. AB - Gastrointestinal vascular malformations can cause haemorrhage requiring multiple transfusions. Surgical or endoscopic therapy are ineffective when the vascular malformations are spread diffusely over the gastrointestinal tract, when lesions escape identification or are not accessible for treatment. Several reports suggest that oestrogen-progesterone therapy is effective in the treatment of epistaxis in hereditary haemorrhagic telangiectasia. The aim of our studies is to test the hypothesis that oestrogen-progesterone is an effective treatment for bleeding gastrointestinal vascular malformations in patients with a very high transfusion need and in whom surgical or endoscopic treatment failed or could not be performed. The mean transfusion requirement prior to entering the studies amounted to 35.4 units packed per patient. In an uncontrolled trial oestrogen progesterone therapy diminished significantly transfusion requirements from 3.4 units packed cells per patient per month to 0.1 units packed cells (p = 0.02). Haemorrhage ceased totally in 3 of 7 patients. A double-blind randomized placebo controlled, cross-over trial shows that therapy with 0.050 mg ethinyloestradiol and 1 mg norethisterone is very effective in reducing transfusion requirements: 2.8 versus 11.2 units packed cells over a 6 month treatment period (p = 0.002). Only 3 of 13 patients treated with ethinyloestradiol and norethisterone required transfusions for persistent bleeding, while 12 of 13 patients in the placebo group had transfusion requirements (p = 0.001). After stopping hormonal therapy, no transfusions were needed for a mean of 10 months. This indicates a long lasting effect of ethinyloestradiol and norethisterone on bleeding and transfusion requirements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342399 TI - Intravenous clonidine does not promote hypoxemia or platelet aggregation in man. AB - This study was designed to evaluate hypoxemia and platelet aggregation in man following intravenous administration of clonidine. With Institutional approval and following informed consent, 20 patients (ASA I-II) without spontaneous or drug-induced coagulation disorder undergoing elective total hip replacement were studied. They were randomly divided into two groups. Group A (n = 10) received an IV loading dose of 4 micrograms/kg of clonidine in 30 minutes followed by an infusion of 1 microgram/kg/h till the end of the procedure. Group B (n = 10) received saline. Platelet aggregation was assessed before infusion and at the end of both the loading dose and the infusion. PaO2 was measured before anesthesia (FIO2 = 0.21), before femoral cementation (FIO2 = 0.40), 2 min. after prosthesis implantation (FIO2 = 1), before the end of the procedure (FIO2 = 0.40) and in the recovery room (spontaneous breathing with FIO2 = 0.21). Plasma clonidine levels were assessed at the end of both the loading dose and the infusion. At any time considered, no statistical differences were noted between the groups for platelet aggregation and PaO2. We conclude that intravenous clonidine does not clinically promote platelet aggregation nor hypoxemia in man. PMID- 8342400 TI - Pulmonary function tests predict outcome after cardiac surgery. AB - The aim of this study was to examine the value of systematic preoperative pulmonary function tests (PFTs) in order to reliably predict prolonged stay in I.C.U., prolonged mechanical ventilation and mortality in elective cardiac surgical patients. 149 consecutive adult patients (valvular replacement or coronary bypass graft) were studied retrospectively. We examined the preoperative respiratory data: vital capacity (VC), first second forced expired volume (FEV1), PaCO2 and PO2. Length of stay in I.C.U. (LICU), duration of mechanical ventilation (DMV), incidence of reintubation and survival rate were used as indices of respiratory morbidity. The results of the present study clearly indicate that patients with impaired airway flow rates had a prolonged postoperative recovery following cardiac surgery. Mortality, ICV and DMV increased when FEV1 was less than 1.5 L, VC was less than 2.5 L, or PaO2 was less than 8.5 kPa. Reintubation was associated with impaired flow rates. Pulmonary function tests appeared effective in predicting postoperative complications and the need for prolonged ventilatory support. PMID- 8342402 TI - Open placebo controlled comparison of the antiemetic effect of droperidol, metoclopramide or a combination of both in pediatric strabismus surgery. AB - In children, strabismus surgery is frequently followed by vomiting. The present study compares the antiemetic effects of droperidol (10 micrograms/kg) and/or metoclopramide (0.1 mg/kg) in 104 children undergoing strabismus surgery. The patients were randomly divided into four groups. Group I (n = 28) received placebo (saline), Group II (n = 26) droperidol 10 micrograms/kg, Group III (n = 25) metoclopramide 0.1 mg/kg and Group IV (n = 25) droperidol 10 micrograms/kg and metoclopramide 0.1 mg/kg. Droperidol was given just after induction and metoclopramide at the end of surgery, just before recovery. The technique of anesthesia involved an anticholinergic premedication, IV fentanyl (2 micrograms/kg), controlled ventilation using isoflurance and N2O in oxygen and systematic gastric emptying before extubation. Vomiting, retching and nausea were noted at 5 different moments: in the Post Anesthetic Care Unit, when arriving on the ward (= after carriage by lift), during the first hour following the return in the ward, from the 6th to the 12th postoperative hour and on the morning of day 1. There was no statistically significant difference in the incidence of vomiting among these four groups. Moreover, the incidence of vomiting in the placebo group was much lower (17.9% in the recovery room, 3.6% at return in the ward, 25% during the first hour, 7.1% from 6 to 12 hours and 3.6% the next day) than that reported in previous studies. We think that this could result from the additive effects of some aspects of the technique of anesthesia described and discussed in this paper. PMID- 8342401 TI - Total intravenous anesthesia in South-African genetic porphyria (variegate porphyria). AB - The authors report the case of a female patient with South-African genetic porphyria who had to undergo hepatic tumorectomy under general anesthesia. The choice for propofol as the induction and maintenance agent using a balanced anesthetic technique led to a significant rise in urinary excretion of porphyrins without associated clinical manifestations. A short review of the literature on physiopathology of porphyrias and medicinal agents, susceptible to induce acute porphyric crisis follows. The authors conclude that the innocuity of propofol as induction and maintaining agent in the porphyric patient cannot be yet established without further studies. PMID- 8342403 TI - The fit of Procera titanium crowns. An in vitro and clinical study. AB - In contrast to conventional casting methods for the production of a metallic crown the Procera process is based on precision machine duplication of models combined with spark erosion of the metal frame. Some of the steps in the manual handling procedure are thereby excluded. The present study evaluated, by means of a replica technique, the fit or adaptation of Procera titanium crowns to the stone die and in vivo to the tooth before cementation. For any combination, the marginal adaptation was superior to and significantly better than the occlusal areas and axial surfaces, respectively. In addition, the crowns had a significantly better fit to the stone die than to the tooth. The marginal discrepancy was approximately 60 microns in vitro and 70 microns in vivo, with a range of 3-205 microns. PMID- 8342404 TI - The amelocemental junction in young premolar teeth. A replica study by scanning electron microscopy. AB - To investigate the validity of traditional data on the frequency of various relationships of root cementum to coronal enamel at the amelocemental junction, the relationship in 50 young premolar teeth extracted on orthodontic indications was documented, using replica techniques for scanning electron microscopy (SEM), combined with polarization microscopy of thin ground sections (< 40 microns). Of 200 surfaces, 30 were excluded because of damage during specimen preparation. Replicas of the other 170 surfaces were photographed at 20x and 80x in SEM and classified as having an edge-to-edge relationship of enamel to cementum in 76% and an overlap of cementum onto the cervical enamel in 14%. What appeared to be a gap between enamel and cementum at low magnification (10%) was seen at high magnification to be a ditch or trough in the cementum: no gaps with exposed dentin were observed in SEM. Polarization microscopy of ground sections of the original specimens confirmed the SEM classification. In this material, the edge to-edge relationship of enamel to cementum predominated: overlapping of cementum onto the enamel was less prevalent than previously reported. The methods applied in this study circumvented some major sources of artefact formation due to shrinkage during specimen preparation, which may previously have caused misinterpretation of 'gap' relationships. PMID- 8342405 TI - The human incisal suture and premaxillary area studied on archaeologic material. AB - The purpose of this study was to investigate the extent of the incisal suture, the size of the premaxillary area, and the developmental status of the dentition. Sixty-three medieval crania were examined: 30 from children and 33 from adults, including 5 cases with tooth deviations. All crania were photographed at a 1:1 scale. From the photographs the size of the premaxilla and the length of the incisal suture were measured. In addition, the spatial conditions in the anterior region were recorded. The study showed that the main closure of the suture takes place shortly after the crowns of the permanent incisors have attained their final width size. The mean size of the premaxillary area was larger in individuals with interincisal spacing and smaller in individuals with crowding when comparing with normal spatial conditions. In the cases of tooth agenesis the premaxillary areas were markedly reduced. PMID- 8342406 TI - On functional strain in some fixed and removable partial dentures. An experimental in vitro study. AB - An 11-unit fixed maxillary reconstruction with 2 bilateral cantilever pontics in combination with a removable partial denture (RPD) with a palatal bar was fabricated. The RPD was retained to the fixed reconstruction with precision attachments. A laboratory model system was constructed in such a manner that the mechanical properties of the biologic supporting tissues involved were simulated by artificial materials. By means of a strain-gauge technique the deformation was studied in both the fixed and the removable partial denture. In different laboratory loading situations with and without the RPD the deformation in the fixed dental appliance was more extensive and more complex when the RPD was excluded. PMID- 8342407 TI - Office and ambulatory blood pressure in patients with craniomandibular disorders. AB - To assess the physiologic response to daily life stress in patients with craniomandibular disorders (CMD), office and ambulatory blood pressure and heart rate were studied in 25 female patients and 25 controls. Significant differences (p < 0.05) were found between the groups for heart rate before the clinical examination and that in the patient group when compared before and after the clinical examination. Higher values were found for mean daytime systolic and diastolic blood pressure in the control group compared with the patient group (p < 0.05). The mean number of systolic blood pressure > or = 140 mmHg during 24 h and daytime was significantly higher (p < 0.05) in the control group than in the patient group. In this study the CMD patients with muscular diagnosis were not more stressed than healthy subjects in the daily activities as evaluated by ambulatory blood pressure measurements. PMID- 8342408 TI - General practitioners' and dental students' decisions on third-molar diagnoses, treatment, and referrals. AB - A questionnaire on third-molar problems was mailed to a systematic random sample of 200 Norwegian general dental practitioners in November 1991. The return rate was 88%. Similar questions were given to 59 5th-year dental students, with a return rate of 83%. Ten third-molar cases were presented by means of copies of radiographs and written information. The following conclusions were drawn: Apart from a terminology problem consisting of lack of discrimination between the terms retention and impaction, overall good diagnostic abilities were shown by both practitioners and students. Receiver operating characteristic analysis of treatment decisions indicated that students were more radical than practitioners. The students had an increased referral rate for third-molar surgery, whereas the practitioners indicated a more selective practice of referring advanced cases. PMID- 8342409 TI - Calcified cartilage zone and its dimensional relationship to the articular cartilage in the human temporomandibular joint of elderly individuals. AB - The aim was to describe the appearance of the calcified cartilage zone (CCZ) and to determine its dimensional relationship to the articular cartilage thickness in the normal human temporomandibular joint. An autopsy material comprising 21 joints from 12 elderly individuals was examined microscopically. The appearance of the CCZ was examined, and the thickness of the CCZ and of the total articular cartilage was measured in 18 different positions in each joint. The CCZ was outlined by a flat or gently undulating tidemark and an irregular osteochondral junction. The cellularity of the CCZ varied extensively. The cells were numerous in the CCZ when the overlying articular cartilage displayed high cellularity. Statistical analysis of the measurements demonstrated a relationship (p < 0.001) between the thickness of the CCZ and of the articular cartilage. Our findings, both qualitative and quantitative, indicate a close relationship between the physiology of the CCZ and of the overlying articular cartilage. PMID- 8342410 TI - Visual selective attention: a theoretical analysis. AB - The present paper outlines a framework which allows a consistent interpretation of data regarding visual selection in visual search tasks. It organizes and reviews visual search tasks in which the target is defined by primitive features, by conjunctions of features and when the target is categorically different from non-targets. The special role of spatial attention is reviewed and different theoretical accounts are discussed. Because visual selection depends principally on the outcome of the early parallel preattentive stage of processing, the main focus will be on this stage. It is concluded that visual selection is to a large extent determined by the physical characteristics of the stimuli present in the visual field. The early preattentive parallel process computes how different each object is from each of the other objects within a particular stimulus dimension. Attention is automatically drawn to the location having the highest activation, implying that the object at that location is automatically selected irrespective of the intentions of the subject. The model also assumes some top-down control. It is well known that attention can be voluntarily directed to nonfixated locations in visual space, varying from a uniform distribution over the visual field to a highly focused concentration. The model assumes that the endogenous direction of attention to an area in the visual field is the only top-down manner of affecting visual selection. Within the area of directed attention, no top-down control is possible: selection is completely determined by the physical properties of the stimuli. PMID- 8342411 TI - [Transurethral echography in the staging of bladder neoplasms]. AB - Forty vesical neoplasias in various stages and which were treated through transurethral resection followed by chemotherapy, in accordance to the currently accepted approach, were studied using transurethral ultrasound techniques. A histochemical correlation is established based on the proposed U.I.C.C. grading (T.N.M.). Such correlation coincides in 88.2% of cases for the "unified" Ta-T1 stage; 70% for T2; 88.8% for T3; and 100% for T4. PMID- 8342412 TI - [Urologic specialization of the Bachelor Andres de Tamayo, famous surgeon and writer of the 17th century]. AB - During the second half of the 15th century and beginning of the 16th century, the problem of "carnosities" and "urine passion" aroused an enormous concern within the social and courtesan environments. The Monarchy, participating in this concern and confronted with a lack of specialized surgeons, fostered the massive hiring of non-college professionals who demonstrated to be knowledgeable in the treatment and cure of this conditions, granting them degrees and nominations so that they could teach and spread their techniques. One of this practical men was the graduate Andres de Tamayo, famous surgeon who worked for Philip II and Philip III, acclaimed writer and poet who in 1617 obtained the degree of surgeon and "urologist" of the Royal Family for his dedication and specialization in "urine passions and carnosities". PMID- 8342413 TI - [Prophylaxis of superficial bladder cancer with 1 mg of intravesical BCG: comparison with other doses]. AB - Presentation of results obtained in 171 evaluable patients from a series of 181, presenting surface vesical cancer in Tis, Ta and T1 stages, treated with 3 different dosages of endovesical BCG as prophylaxis for tumour relapse: a) high dose, 100 to 120 mg, 72 patients; b) intermediate dose, 20 to 50 mg, 39 patients; and, c) minidose of 1 mg, 60 patients. Complications and adverse reactions were seen to be dose-dependent, also percentage of patients free of disease both after treatment and following addition of retreatment in several patients was similar in all the dosages used. It is thus concluded that endovesical BCG 1 mg, would be an optimal dosage for the prophylaxis of surface vesical cancer relapse. PMID- 8342414 TI - [Microdoses of BCG vaccine for prophylaxis in bladder cancer stage T1]. AB - A prophylaxis with a minidose of BCG Vaccine (1 mgr.) is performed in vesical instillation during one year, to 108 patients bearing bladder cancer in the stage T1. In the first month the instillations are once a week, each fifteen days the second and third month and then, once a month for one year. An 19.4% of recurrences is obtained with an general average observation time of 37.3 months as well as an important increase of muster populations of T lymphocytes and a positive test of dinitroclorobenzene. As complications we have obtained an inguinal BCG adenitis and in a few cases disury and frequency for two or three days. We conclude that the doses of the BCG vaccine used during the period of one year, is satisfactory in the reduction of recurrences and without important complications. PMID- 8342415 TI - [Our experience in the treatment of cystine lithiasis]. AB - Contribution of six cases of patients with cystinic lithiasis, diagnosed and treated at our centre. Analysis of pathophysiological mechanisms, key data for their diagnosis and current aspects of treatment, as well as a review on past and recent literature on this disease. PMID- 8342416 TI - [Vesico-intestinal fistulae]. AB - Review of vesicointestinal fistulae cases treated in the Urology Unit at our hospital over the last few years. Most frequently seen cause was colorectal cancer (66%) and most frequent location was vesicosigmoideal (50%). Clinical signs and symptoms were varied, mainly urinary infection in 100% cases, pneumaturia in 66% and fecaluria in 50%. Opaque enema and cystography were great diagnostic aids as complementary methods. Also U.I.V., cystoscopy, rectoscopy and C.A.T. were used. Treatment was surgical in all cases where the patient's general health status allowed it. PMID- 8342418 TI - [Synergistic necrotizing fasciitis of genitalia and perineum. Our experience]. AB - Presentation of 9 cases of synergistic genitalia and perineum necrosing fascitis treated in our service over the last 5 years. The contents of the disease and its terminology has been reviewed by the light of the existing literature. In our series, patients mean age was 65 years. Three of our 9 patients had diabetes mellitus, and also 3 had liver disease due to alcohol. The initial septic focus was found in 8 cases, and in 4 it was urological, basically urethra's stricture. The most frequently involved germs were aerobe-anaerobe associations. Mortality was 11%. PMID- 8342417 TI - [Prognostic value of the tissue expression of human chorionic gonadotropin (beta HCG) in infiltrating transitional carcinoma of the bladder]. AB - Study of the ectopic secretion of Human Chorionic Gonadotrophin (beta-HCG) in the tumoral tissue of 62 patients diagnosed with infiltrant transitional carcinoma of the bladder. The inmunohistochemical tests showed specific stains in 15/62 patients. Bi-varied analysis showed that vesical tumours with beta-HCG ectopic expression present associated nodular disease with a significantly higher prevalence (p = 0.02). Survival of patients with beta-HCG+ tumours was overall lower that of patients with beta-HCG-tumours, but this difference did not reach statistical significance. Multivariate analysis of survival showed no prognostic value for the tissue expression of beta-HCG, when it is considered as an isolated variable. Complete local response was seen in 5/6 beta-HCG+ patients treated with pre-operative chemo and radiotherapy and in 1/4 patients treated with pre operative radiotherapy. Tissular expression of beta-HCG is a poor prognostic factor due to its relationship with another 2 variables of larger predictive capability: the presence of metastatic nodular disease and the infiltration of venous and/or lymphatic structures of the vesical wall. PMID- 8342419 TI - [Vesiculography with echo-guided transperineal puncture: a complement to intracavitary transrectal echography]. AB - The present paper is a presentation of our experience in the study of seminal vesicles through transperineal ultrasound-guided puncture vesiculography (T.U.P.V.). Explanation of the technical procedure, performance of an analysis of indications and evaluation of its advantages and disadvantages. We consider that T.U.P.V. is another technique to further study the processes affecting the seminal vesicles. PMID- 8342420 TI - [Obstruction caused by anterior urethral valves in childhood]. AB - Presentation of 3 patients (aged 11 years, 9 months and 9 years old) with diaphragm-like valves in the anterior urethra. Haematuria, urinary tract infection and thin voiding stream were the most common symptoms. Transurethral endoscopic resection with cold blade solved the problem appropriately in two cases, though the youngest patient required resection of stenotic area and end terminal by-pass of the urethra. PMID- 8342421 TI - [Associated renal malformations. Renal agenesis and ectopy]. AB - The association of ectopia and renal agenesis is not a common occurrence. Incidence is variable although in the clinical practice it usually represents 1/900-1500 visits, and occurs in the absence of one kidney in 10% of pelvic ectopias and accompanied by genital deformations in 50% of cases. A large number of cases present no symptoms and the diagnosis happens by chance during an X-ray examination for other reasons. In further occasions other urological manifestations lead to the discovery. Treatment is usually conservative and expectant, and surgery becomes necessary only when is inductive of infectious and obstructive symptoms that might compromise the organ's viability and the patient's life. PMID- 8342422 TI - [Diagnosis of prostatic abscess with echography]. AB - Report of our experience in 15 cases of prostatic abscess where diagnosis was established by ultrasound techniques. Most frequent images were: irregular and heterogenical hyperchoic areas. PMID- 8342424 TI - [National uro-oncologic registry]. PMID- 8342423 TI - [Arteriovenous fistulae following percutaneous renal biopsy in renal transplantation. Selective arterial embolization]. AB - Five cases of clinically severe arteriovenous fistulae (AVF) secondary to percutaneous renal biopsy in patients carrying a functional renal graft were diagnosed and treated in our centre. Occlusion via superselective intraarterial embolization accomplished successful control in every case. We insist on the therapeutical value of this minimally invasive technique, which furnish it with a particularly relevant role in renal transplantation. PMID- 8342425 TI - [The diagnosis of infravesical obstruction]. PMID- 8342426 TI - [Conceptual review of oncocytic lesions]. AB - Updating of a series of entities which significance is not always pathological, or it is poorly known, and which are related to oxyphilic transformation of epithelial cells. Review of concepts such as "oncocytosis", "oncocytic hyperplasia" and "oncocytoma", establishing a hypothetical continuum of damage which could actually be contemplated within the evolution spectrum of hyperplasia adenoma-carcinoma. Also, both the changes occurring at subcellular level and the hypothesis considered to explain them are commented. PMID- 8342428 TI - [Multivariate analysis of local response to preoperative treatment in patients with infiltrating carcinoma of the bladder]. AB - The article presents a multivariate study carried out by means of a logistic regression of local responses (reduction to stage p0, p1 or p 'in situ') in 82 patients with transitional infiltrant carcinoma of the bladder, undergoing 3 different types of radical therapy: 25 patients treated with TUR and radical cystectomy; 33 patients treated with TUR, pre-operative radiotherapy (45-60 Gy) and radical cystectomy; and 24 patients treated with TUR, intra-operative radiotherapy (15 Gy), external radiotherapy (46 Gy), neo-adjuvant chemotherapy and radical cystectomy. Local response increased with the intensity of pre operative therapy, there being a better relationship with this approach than with the initial clinical stage of the tumour. The factors which better explain the prospect of an objective local response are the use of radiotherapy associated to chemotherapy and the absence of metastatic lymphatic nodes. These 2 variables can adequately predict the local response in 87% of patients. PMID- 8342427 TI - [Response of superficial bladder carcinoma to prophylacit treatment with mitomycin-C versus interferon. Preliminary study]. AB - The efficacy of two protocols for the prevention of relapse using Mitomycin-C and alpha-Interferon in 56 patients with surface bladder carcinoma (stages Ta-T1) treated with TUR was compared in a prospective study. Relapse percentages and rates, related to the tumours' presentation characteristics (single, multiple, primary, recurrent), as well as their systemic and local toxicity, were evaluated. The study of statistical significance is made using the squared-chi test, and it is completed with a Fisher's test for groups containing few elements for accuracy. The results show no statistical differences (log rank p = 0.313) between the two groups of endovesical therapy, both confirming to be effective as adjuvant therapy to TUR in surface bladder tumours. PMID- 8342429 TI - [Endoscopic trigono-cervico-prostatotomy: our experience]. AB - Presentation of our experience in treating the disease of the vesical neck through longitudinal endoscopic transurethral incisions in 24 patients following the Orandi procedure. Of the 24 patients seen in our service, 21 showed a clear clinical and urodynamic improvement. Complications were 2 cases of epididimorchitis and 1 iatrogenic stenosis of the anterior urethra. There were no major haemorrhages, urinary incontinence, or retrograde ejaculation except for an obvious decrease of ejaculate volume in 2 cases. PMID- 8342430 TI - [Primary Kaposi's sarcoma of the penis in a patient with acquired immunodeficiency syndrome]. AB - Presentation of one case of a 40 year-old, homosexual, AIDS diagnosed male with extrapulmonary tuberculosis (lymphatic nodes) and prior history of gonococcal urethritis, brain toxoplasmosis, molluscum contagiosum and pneumonia by Pneumocystis carinii. A purpura-type lesion with inflammatory features appeared in the foreskin which was diagnosed as primary Kaposi's sarcoma of the penis. The article explains the clinical signs and symptoms, laboratory data, histological findings, and it reviews the literature. PMID- 8342431 TI - [Ureteral obstruction secondary to endometriosis. Report of a case]. AB - The urinary tract is rarely affected by endometriosis, urinary bladder being the most common location. This paper presents one case of advanced extrinsic endometriosis which initially presented as obstructive pyelonephritis. The diagnostic methodology, including uro-tomographic imaging, is evaluated. Although good results have been reported with hormone-therapy, we support the surgical approach sanctioned by the patho-anatomical findings. PMID- 8342432 TI - [Conservative treatment of Wunderlich syndrome in a functional monorenal patient]. AB - Presentation of one case of Wunderlich's syndrome secondary to spontaneous mesorenal fracture due to renal angiomyolipoma. In our case, the therapeutical approach is based in the need to preserve the functional renal unit. Wunderlich's syndrome or spontaneous perirenal haematoma can occur for a variety of causes, the most frequent ones being renal adenocarcinoma and renal angiomyolipoma. The latter is a hamartoma made up of three different tissue lines: smooth muscle cells, blood vessels and adipose tissue. Based on our case, we discuss the clinical, prognostic and therapeutical aspects related to renal angiomyolipomes. PMID- 8342433 TI - [Synchronous and bilateral inverted papilloma of the kidney pelvis. Conservative treatment]. AB - Contribution of a new case of inverted papilloma (IP) of the upper urinary tract (UUT) with the idiosyncrasy of being bilateral and synchronic, a fact not found in the reviewed literature, treated with radical surgery on the left side and conservatively on the right one. Discussion on this pathology is addressed, emphasising its benign biological behaviour, which does not eliminate some cases of malignization. Treatment has to be conservative, and so we stress the relevance of defining a suspicion state to make pre- and peri- operative diagnosis in which endourological methods, that allow both direct visualization and the taking of a biopsy, play a preeminent role. Subsequent strict monitoring is essential due to the likelihood of relapse and malignant changes. PMID- 8342435 TI - [Spontaneous bladder rupture: report of a case]. AB - Contribution of one case of spontaneous vesical fracture in a patient with no urinary pathological background. Presentation of this picture is highly uncommon. In this case, a major alcoholic intake stands out as the unleashing factor which provoked vesical overdistension with an intraperitoneal posterior fracture. A review is made of the various etio-pathogenic mechanisms which can originate this pathology, as well as the diagnostic and therapeutic methodology. PMID- 8342434 TI - [Renal oncocytoma in acquired cystic diseases]. AB - The authors report a case of renal oncocytoma associated with acquired renal cystic disease and we comment on its pathogenesis and course. This case responds a patient with chronic end renal insufficiency, included in a maintenance hemodialysis program for the two previous years nefrectomy. The association of oncocytoma with acquired renal cystic disease has been previously described only twice; both patients have been hemodialyzed for a long time. PMID- 8342436 TI - Fascism and the eye of the beholder: a reply to J. S. Searles on the controlled intoxication issue. PMID- 8342437 TI - Smoking in pregnancy: a follow-up study of women unwilling to quit. AB - During a smoking intervention trial at Buskerud Central Hospital in Norway in 1988-1989, 79 out of 279 smoking pregnant women refused any form of intervention. Thirty-five of the women (44%) expressed a negative attitude to quit smoking and insisted on continuing their smoking habits. Forty-four (56%) indicated a positive interest in quitting, but refused advice and assistance from the health service. The smoking pattern of the 79 women was followed during 12 months. In spite of their stated unwillingness to change their smoking habits, or their refusal of advice, no difference was observed in their quitting or reduction rate during pregnancy compared to a control group of women with a positive interest in quitting. In addition, significantly more women in the latter group actually increased their smoking. The quitting rate of the negatively motivated women also proved similar to that obtained in a stop-smoking intervention used among positively motivated women who also had received additional information. Hence, the negatively motivated do not appear to represent a graver risk group than other pregnant women. PMID- 8342438 TI - In search of an alternative placebo: estimating alcohol content of nonalcoholic, light, and regular beer. AB - Alcohol research has demonstrated that expectancies about what one has consumed may supercede pharmacological effects of the drink. The present study sought to expand the scope of the placebo designs by examining an alternative manipulation, using widely available nonalcoholic beverages. The nonalcoholic beers used in this study have recently become marketed and made available to consumers by two major breweries. Subjects were provided with a total of four beer samples: two nonalcoholic samples ("O'Doul's" and "Sharp's"), one light sample ("Busch Light"), and one regular sample ("Busch"). Results indicated that subjects estimated the alcohol content in "O'Doul's" as significantly lower than that of the light and regular beers; the estimate of alcohol content in Sharp's was not significantly lower than either the light or regular beers. In addition, the mean alcohol estimates for both nonalcoholic beers approximated the actual alcohol content of a light beer (roughly 3%). These results indicate that nonalcoholic beers may provide a viable alternative to the placebo manipulations currently in vogue. PMID- 8342439 TI - Morphine and human aggression. AB - Twenty-eight male undergraduates received either 45 mg of immediate-release oral morphine tablets or a placebo. Subjects were then given the opportunity to administer electric shocks to an increasingly aggressive bogus opponent during a competitive reaction-time task. Subjects in the morphine condition were more willing to initiate attacks against their opponent than subjects in the placebo condition, and reacted more aggressively at all levels of provocation. PMID- 8342440 TI - An expert system intervention for smoking cessation. AB - Intervention efficacy can be increased when the treatment is maximally matched to the needs of the client. One means of achieving such matching is through use of an expert system, a computer-based decision-making system designed to utilize client information to produce unique, matched information and interventions. An expert system can combine the individual matching possible in a clinic-based intervention and the low cost associated with a public health approach. This paper begins by discussing several alternative implementations of the expert system approach within the general context of communication theory. Second, the theoretical model and related empirical evidence which form the basis of the expert system is described briefly. Third, the details of a computer-driven, expert system intervention specifically developed for smoking cessation is described. Finally, empirical results from a study comparing the expert system intervention to three alternative interventions for smoking cessation are presented. In general, the expert system approach can provide a cost effective, viable, and efficacious means of intervening in a specific problem behavior area. Implications and potential areas of development are discussed. PMID- 8342441 TI - Hangover moderates the association between personality and drinking problems. AB - This study investigated hangover as a potential mediator or moderator of the relation between personality and drinking problems. Hangover did not appear to mediate the relation, suggesting that the link between personality and drinking problems does not stem from an indirect effect via hangover. Hangover did appear to moderate the relation. Personality and drinking problems correlated significantly for subjects who reported experiencing severe hangovers, but not for those who reported mild hangovers. Those who experience greater hangover may choose to drink more alcohol in order to relieve these adverse effects, and this choice may vary with personality. The theoretical and conceptual implications of mediators and moderators are also discussed. PMID- 8342442 TI - Additive effects of mood and eating forbidden foods upon the perceptions of overeating and binging in bulimia nervosa. AB - We examined the relationship between actual caloric intake and subjective perceptions of amount eaten using self-monitoring data. Forty subjects participated in the study: 20 bulimia nervosa patients and 20 normal controls. All subjects monitored their eating for a 2-week period and rated each eating episode on a Likert-type scale ranging from an undereat to a binge. Estimates of actual caloric intake were compared with these subjective ratings. Bulimics were found to overrate the amount consumed, relative to controls. The effect increased as caloric intake increased. Bulimics' ratings of amount eaten and binging were found to be predicted by the estimate of the actual amount eaten, the type of foods eaten, and the subjects' mood prior to eating, while nonbulimics' ratings were predicted only by the estimated actual amount. Subjective ratings of amount were found to be the best predictor of purgative activity. The results are discussed in terms of a perceptual bias theory, treatment implications, and possible revisions to the current DSM criteria for bulimia nervosa. PMID- 8342443 TI - Attributional correlates of cessation self-efficacy among smokers. AB - Male and female smokers (N = 121) stated the most important cause of previous abstinence failure and rated this attribution along the dimensions of internality, stability, globality, and controllability. Respondents also estimated their ability to abstain from smoking in a variety of hypothetical situations (i.e., cessation self-efficacy). Results indicated that high self efficacy smokers attributed prior abstinence failure to motivational and situational factors more frequently than low self-efficacy smokers. Significant correlates of cessation self-efficacy included perceived success of prior quits (r = .26), percent of family/friends who smoke (r = -.21), causal stability (r = .18) and causal control (r = .21). Composite attributional indices of behavioral self-blame and the abstinence violation effect also correlated significantly with cessation self-efficacy (rs = .21 and .22, respectively). Consistent with self efficacy theory, these findings suggest that personal experience, vicarious experience, and attributional processes play a role in one's perceived ability to refrain from smoking. PMID- 8342444 TI - Reasons for smoking or not smoking in early adolescence. AB - Previous studies of smokers' and nonsmokers' reasons have not compared their reasons for smoking and their reasons for not smoking, or examined the extent of change or stability in these reasons over time. We examined reasons for smoking and not smoking in a large sample of 13-year-olds from the general population. Factor structures of reasons differed according to whether adolescents were smokers or nonsmokers. Nonsmokers were found to be less discriminating than smokers about the reasons for smoking. Smokers and nonsmokers tended to show more agreement about the reasons for not smoking. Recency of smoking was differentially related to the factors for smoking and the factors for not smoking. "Image" was a more important reason for smoking at age 11 than at age 13. "Friends" as a reason for smoking showed a small degree of consistency across age, whereas reasons involving relaxation and pleasure showed a relatively higher degree of consistency. Health, as a reason not to smoke, showed only a small degree of consistency, while social context, effects and access were moderately consistent as reasons not to smoke at ages 11 and 13. PMID- 8342445 TI - Disinhibition and negative affectivity in substance abusers with and without a gambling problem. AB - A cohort of 2,171 substance abusers were assessed for their gambling behavior, and divided into three groups: those with no significant gambling problem (87%); those with a probable problem (7.2%); and those with a severe problem (5.8%). Substance abusers with a gambling problem scored significantly higher on measures of: impulsivity; disinhibition of aggressive/hostile responses; and negative affectivity. They also abused more substances than the nongamblers. The results underscore the importance of assessing a wide range of impulsive behaviors in substance abusers and the potential for subtyping substance abusers based on psychological traits. PMID- 8342446 TI - The cast-6: development of a short-form of the Children of Alcoholics Screening Test. AB - The 30-item Children of Alcoholics Screening Test (CAST) is shortened to a 6-item scale (CAST-6) using Principal Components Analysis of CAST responses for three distinct samples: outpatient substance abusers, outpatient psychiatric patients, and medical students. The face validity, internal consistency, and discriminatory ability of the CAST-6 are examined. The CAST-6 is judged to compare favorably with the full CAST and to provide a more efficient way to identify adult children of alcoholics. PMID- 8342447 TI - Changes in family functioning during treatment and drinking outcomes for high and low autonomy alcoholics. AB - Alcoholics' level of autonomy was hypothesized to have a moderating effect on the relationship between changes in family functioning and subsequent drinking behavior. Functioning of families of patients in outpatient alcoholism treatment was assessed prior to the onset of treatment and again 6 months later. For alcoholics who were low in autonomy, perceptions of improvements in functioning predicted better drinking outcomes during a subsequent 6-month follow-up, while changes in family functioning were unrelated to drinking behavior in high autonomy alcoholics. The areas of family functioning in which change was a significant predictor of later drinking primarily concerned the quality of interactions between family members. Alcoholics' gender, psychiatric comorbidity, and the type of treatment they received did not moderate the relationship between changes in family functioning and drinking outcomes. Implications for the treatment of alcoholic patients and the limitations of the research are discussed. PMID- 8342448 TI - Tolerance in gambling: an objective measure using the psychophysiological analysis of male fruit machine gamblers. AB - "Excitement" has often been referred to as the gambler's drug although until recently there was little evidence to substantiate such claims. This study involved the systematic monitoring of the psychophysiology of fruit machine gambling using heart rate measures in 30 adolescent male gamblers. The study was designed to test heart rate differences between regular and nonregular fruit machine gamblers (i.e., between subjects) and differences against the players' own baseline rates (i.e., within subjects). Results showed that there were no heart rate differences between regular and nonregular gamblers although during gambling, both groups' heart rates increased by approximately 22 beats per minute. It was also found that nonregular gamblers' heart rates did not decrease significantly after gambling whereas regular gamblers did. This finding could be argued as the first study to demonstrate an objective measure of gambling tolerance. PMID- 8342449 TI - Evaluation of the effect of contraceptive prices on demand in eight Western European countries. AB - Wide differences exist among European countries as regards national reimbursement schemes and the resulting individual expenditure on contraception. In this current research project annual expenditure and costs in the first year of use were calculated, taking into account existing reimbursement levels, for oral contraceptives, intrauterine devices, condoms, and sterilization in eight Western European countries: Italy, France, United Kingdom, Spain, West Germany, Austria, Sweden and Denmark. The costs were expressed in Swiss francs. For users of oral contraceptives it emerged that the annual expenditure on contraception ranged from nil in the United Kingdom to 172.32 Swiss francs in Austria. In the case of condoms, the cost to users was lowest in the United Kingdom (57.44 Swiss francs) and highest in Spain (105.95 Swiss francs). Expenditure on the use of an intrauterine device in the first year ranged from nil in the United Kingdom and Sweden to 449.87 Swiss francs in Austria, while sterilization was carried out free of charge in France, West Germany and Denmark, as compared with a cost of 677.57 Swiss francs in Italy. The variation in expenditure was largely explained by the extent to which contraception costs are reimbursed in the respective countries. Correlation of the calculated expenditure on a method and its use did not show any statistically significant trend. This suggests that the wide differences in the choice of contraceptive methods between countries are not related to differences in national reimbursement schemes and resulting costs to users, and that other factors must be involved. PMID- 8342450 TI - Contraceptive practice and attitudes in former Soviet women. AB - For decades, abortion has been the principal birth control method for Soviet women. As indicated by some earlier local surveys, most couples use unreliable methods. Little is known about the latest trends in contraceptive use affected by the recent general liberalization of Soviet society, including more open attitudes about sex. A survey was conducted in 1991 via a questionnaire in the popular 'Health' magazine with national circulation. A total of 8059 women returned the questionnaire. The sample is selective with an overrepresentation of young and better educated urban residents, mostly from Russia and the Ukraine. Some 81% reported use of a contraceptive method during the last 5 years. Traditional methods still prevail (41% used withdrawal, rhythm and douche). Among women younger than 25 years there is a clear trend toward use of modern methods (IUD 35% and the pill 10%), although their notion of the 'pros" and 'cons' is biased. Of the respondents, 20% used a barrier method, mainly condom. The preferred method is the IUD (51%) and the pill (18%). Abortions resulting from contraceptive failure were reported by 60% of women. Eighty-nine percent considered pregnancy termination more dangerous than its prevention. For only 12% of respondents, a physician was the main source of contraceptive information, although 49% addressed him for advice. The results indicate a gap between conservative birth control practice and preferences of Russian women, with a positive general trend in the near future. PMID- 8342451 TI - A multicenter clinical trial in Nigeria with a low-dose oral contraceptive, Marvelon. AB - The monophasic combination preparation, Marvelon, is a modern, technically improved oral contraceptive. It was tested for contraceptive reliability, cycle control and acceptability in 4 clinical centers in Nigeria for a period of one year. A total of 408 women was included in these studies, and 3102 cycles were monitored. The results showed a high contraceptive reliability and an excellent cycle-control. It was well tolerated. There were very few side-effects and the symptoms during medication were minor and hardly needed any treatment. At 12 months, 43.1% of the acceptors were still in the trial. Seventy-nine women (19.4%) discontinued before the end of the study for any reason. Drop-out reasons of these women were mainly non-medical. For the remainder of drop-outs no reason was given. This study suggests that this new oral contraceptive adequately satisfies the contraceptive needs of modern women. PMID- 8342452 TI - Introductory trial of the once-a-month injectable contraceptive, Cyclofem, in Indonesia. AB - Cyclofem, a once-a-month injectable hormone contraceptive, contains medroxyprogesterone acetate, 25 mg and estradiol cypionate, 5 mg. Indonesia is one of the countries participating in an introductory trial in collaboration with the World Health Organization (WHO) under the Human Reproduction Program (HRP). The main purpose of the trial is to assess, through a limited cohort of users, both problems and user needs in the program situation with regard to safety, efficacy, acceptability, and causes of discontinuation in the Indonesian context. Data based on the trial (March 1990-February 1992) indicate that the Cyclofem women complained of dizziness, nausea, bleeding problems, migraine, vomiting, amenorrhea, allergies and hypertension during the use of Cyclofem. However, it was found that the complaint rates decreased with increased duration of use. The life table continuation rates indicate that about 80% and 66% continued use at the end of 6 months and 12 months, respectively. Personal reasons account for the highest proportion of discontinuation, followed by desire for pregnancy and lost to-follow-up. PMID- 8342453 TI - Evaluation of liver function and lipid metabolism following Norplant implant removal. AB - A final evaluation of this longitudinal study involving 100 Singaporean women shows that, besides a significantly elevated bilirubin level, there is no other evidence of hepatocellular dysfunction with the use of Norplant implants. The elevated bilirubin levels remained significantly elevated six months after removal of the implant. Despite this, all values of bilirubin remained within the clinical range for the population studies. As regards lipid metabolism, total cholesterol, LDL-cholesterol and total triglycerides continued to remain below the pre-insertion mean at six months post-removal. The HDL-cholesterol showed a significant increase following removal of the implants. As a result, the HDL cholesterol/(total cholesterol-HDL-cholesterol) ratio continued to remain above 0.200. This indicates that Norplant implants are not directly contributory to cardiovascular risk. PMID- 8342454 TI - Evaluation of hemostatic function following Norplant implant removal. AB - Norplant implant use in Singapore showed a decrease in vitamin K-dependent Factors II, V, VII and reduction in fibrinolytic activity at the end of 5 years of use. Increased platelet numbers and accelerated platelet aggregation were also found throughout the 5 years of Norplant use. It thus appears that unlike the combined pill, prolonged Norplant use does not activate the coagulation system and does not enhance a state of hypercoagulation. On removal of the Norplant implants at the end of 5 years, the significant changes seen in hemostatic function observed with Norplant use remained. PMID- 8342456 TI - Intracervical anchoring: a new approach to intrauterine contraception. AB - The intracervical device described in this paper consists of copper wire around a small plastic frame that is anchored to the inner wall of the cervix, at about 1.5 cm from the external os. The device represents a radical departure from conventional intrauterine contraception and 'frameless' IUDs, which are anchored to the uterine fundus. The device was evaluated in a preliminary study of 11 women. During the 3-month evaluation period, there were no expulsions or removals for any reason. The device was well tolerated. Expanded clinical trials are planned. PMID- 8342455 TI - A multicenter study of the clinical performance of the Ortho Gyne-T380 Slimline intrauterine device in routine use in general practice and family planning clinics. UK Family Planning Research Network. AB - In a multiclinic use-effectiveness study, 505 parous women were fitted with an Ortho Gyne-T380 Slimline intrauterine device (IUD). Gross cumulative event rates, calculated by the Tietze-Potter life-table method, show the device to have a very low pregnancy rate and a low expulsion rate. The rate of removal following complaints of bleeding and/or pain was high. The incidence of infection was low and more likely to occur among younger users. The older parous women were more likely to have a satisfactory experience of IUD use than younger users. In accordance with current advice, and following a full discussion with the client, long-term use of the device beyond the manufacturer's recommended time period will continue among satisfied users. PMID- 8342457 TI - Ovarian function during hormonal replacement therapy in perimenopausal women. AB - To determine the need for contraception during Hormonal Replacement Therapy (HRT) in perimenopausal women, ultrasound monitoring of ovarian function was performed on 10 perimenopausal women in the second month of treatment. All patients were not at risk of unwanted pregnancy during the study period and had last regular menses at least three months before starting HRT. All of them received transdermal implants of 50 mg of estrogen, twice per week, and 10 mg of oral dydrogesterone on the fourth week. Ultrasound performed at treatment days 7, 14 and 21 of the second month revealed follicular development and rupture in 5 out of the 10 patients. Contraceptive implications are discussed. PMID- 8342459 TI - The new intrauterine contraceptive devices: safe and effective. AB - Reviews of the safety of intrauterine contraception usually are based on studies that do not reflect changes in clinical practice that have occurred over time, and that include many types of IUDs that are no longer used. Studies of insertions of the Multiload 375 and Copper T 380 performed since 1980, which more accurately reflect current clinical practice, show that these IUDs provide a high level of protection against pregnancy and are associated with low rates of complications. Current clinical opinion regarding the safety of IUDs needs to be reassessed in light of the positive safety record of these IUDs. PMID- 8342458 TI - Clotting factors after emergency contraception. AB - Women with a previous history of thromboembolic disease have often been denied oral emergency contraception because of a theoretical concern about increasing their risk of thrombosis. METHODS: Eleven healthy volunteers with regular periods were recruited to the study. A thrombophilia screen was done at the first visit and they each had four measurements of Factor VII and antithrombin III taken at mid-cycle for two cycles. In the third cycle, emergency contraception was given mid-cycle and blood samples were taken 1, 3 and 7 days later. A further four samples were taken during the following cycle and, where the cycle had been significantly foreshortened due to the emergency contraception, a fifth cycle was monitored. The treatment given during the third cycle was the standard Yuzpe regimen of emergency contraception, which consists of 100 micrograms of ethinylestradiol and 500 micrograms of levonorgestrel repeated after twelve hours. RESULTS: There was a wide inter- and intra-subject variation in clotting factors in the observation months. There was no obvious effect noted in the levels of the factors measured after treatment, either in the first week or in the subsequent month(s) of follow-up. CONCLUSIONS: The dosage of ethinylestradiol used in emergency contraception is very shortlived and this study shows no effect on clotting factors. This suggests that ethinylestradiol should not be automatically dismissed in women with previous thromboembolic disease. PMID- 8342460 TI - Rapid absorption and local redistribution of progesterone after vaginal application in gilts. AB - Catheters were implanted in 6 anaesthetized gilts (3 animals in the follicular phase, 3 in the luteal phase) into a carotid artery and into the utero-ovarian vein and uterine artery on both sides. The uterine lumina were closed by a suture. Further, a catheter was inserted into the vagina after which the animals were allowed to recover. Tritiated progesterone was infused into vagina the following day during a 2 min period and simultaneous blood samples collected from the 5 catheters every 10 min for 2 h after which the animals were sacrificed. Tissue samples were obtained from the genital organs. The results showed a rapid absorption of progesterone from the vaginal lumen and a marked redistribution to the genital organs. The increased level of radioactivity in the plasma samples collected from the uterine arteries compared to the simultaneous samples from the carotid artery in 2 of the 3 animals in the luteal phase indicates the existence of a local redistribution system. PMID- 8342461 TI - Clinically diseased cats with non-suppurative meningoencephalomyelitis have Borna disease virus-specific antibodies. PMID- 8342462 TI - Aerobic bacteria occurring in the vagina of bitches with reproductive disorders. AB - A retrospective survey was performed of aerobic bacterial species found in the vagina of 203 bitches with genital disorders, e.g. infertility, vaginitis, pyometra and puppy death. Escherichia coli, beta-hemolytic streptococci, Staphylococcus intermedius and Pasteurella multocida were the species most often isolated. From bitches with pyometra E. coli in pure culture was the most frequent isolate. In contrast, the majority of infertile bitches gave rise to mixed cultures, and no specific bacterial species was consistently associated with infertility. Thus, bacterial sampling from infertile bitches was concluded to be of low diagnostic value. Bacterial species isolated from the bitches having vaginitis were present in pure culture in 26.9% of the samples while nonspecific mixed cultures were obtained from 34.6% of the samples from these bitches. E. coli was the most frequently isolated bacterial species from bitches with dead puppies. However, in such cases it is important to relate the vaginal bacterial findings to autopsy findings and the results of bacteriological cultures of the pups. PMID- 8342463 TI - Bovine uterine, cervical and ovarian cytosol estrogen and progesterone receptor concentrations in cystic ovarian disease. AB - Bovine cytosol estrogen (ERC) and progesterone receptor (PRC) concentrations were measured simultaneously in various regions of the uterus and in ovarian stromal tissue in cows with cystic ovarian disease (follicular cysts), and the concentrations compared with those in animals with normal cycles. In cystic ovarian disease, ERC concentrations in endometrium (550 fmol/mg cytosol protein (c.p.)) and in myometrium (405) were significantly higher than in control animals. Very high PRC contents were measured in the endometrium (3115) and myometrium (2761) of cows with cystic ovarian disease. In control animals, PRC concentrations in the endometrium and myometrium were significantly lower than in diseased animals. No statistical differences were observed in ERC or PRC contents between the endometrium and the myometrium in cows with cystic ovarian disease. ERC and PRC concentrations in the uterine cervix and ovaries were low compared to those detected in the uterus. Bovine serum estradiol-17 beta concentrations were higher (p < 0.001) in cows with cystic ovarian disease than in control animals in postpartum anestrus or during the normal estrous cycle. Serum sex hormone-binding globulin (SHBG) concentrations were of the same magnitude as in control cows during their estrous cycles. These findings show that long standing low endogenous progesterone and elevated estradiol concentrations in serum are associated with elevated ERC and PRC concentrations in bovine uterus. PMID- 8342464 TI - Tick-borne fever in lambs of different ages. AB - Four groups of lambs aged 1 week, 4 weeks, 1/2 year and 1 year old respectively were inoculated with Ehrlichia phagocytophila infected blood. Clinical signs, temperature reactions, haematological changes and parasitaemia were more moderate in lambs inoculated with E. phagocytophila at the age of 1 week than those recorded in the older animals. The clinical response to tick-borne fever (TBF) appears to be more severe with increasing age of the lambs. The lymphocyte reactivity to mitogens was reduced in the TBF infected lambs, and was most pronounced in lambs in the 3 older age groups. PMID- 8342465 TI - Vitamin D status and hypocalcemic response to protamine in exercised and non exercised dairy cows. AB - Bone resorption was studied in post parturient cows using intravenous injection of protamine. Protamine inhibits bone resorption and the protamine-induced hypocalcemia can be taken as a measure of this process. The studies were performed in a herd where half of the cows had been tied indoors for 2 1/2 years, the other half had been given daily exercise during the same period. All animals were fed in the same way. The hypocalcemic response to protamine was the same in both groups, which indicates that exercise did not change bone resorption. The serum levels of calcium, inorganic phosphorus and magnesium around parturition did not differ. The daily exposure to daylight increased the serum level of 25 (OH)-cholecalciferol in late summer in the exercised group. PMID- 8342466 TI - The effect of transport stress on plasma levels of catecholamines, cortisol, corticosteroid-binding globulin, blood cell count, and lymphocyte proliferation in pigs. AB - The effect of transport stress on the plasma levels of catecholamines, cortisol, and corticosteroid-binding globulin were studied in 6 gilts. To assess the effect on immune status, white blood cells were also counted and the cell-mediated immunity was estimated. The adrenaline level increased significantly during transport, from a basal mean level of 0.03 ng/ml to a plateau level of 0.11 to 0.12 ng/ml. The noradrenaline level fluctuated, but not constantly, during transport. The mean plasma cortisol level before loading was approximately 40 nmol/l and rose immediately after the start of transport to 70 nmol/l (p < 0.05) and to 87 nmol/l (p < 0.01) within 10 and 30 min, respectively. After unloading the cortisol level rapidly decreased and a minimum level was seen 4 h after the transport, whereafter the diurnal rhythm was resumed. The plasma corticosteroid binding globulin level increased nonsignificantly during the day of transport, from 25 nmol/l to a level of 34 nmol/l, and it continued to increase until a plateau level was reached on the second day after transportation. The total white blood cell number increased significantly (from 13.7 to 15.5 x 10(9) cells/l), the number of lymphocytes decreased significantly (from 8.4 to 7.0 x 10(9) cells/l), and the number of polymorphonuclear neutrophils increased significantly (from 4.3 to 7.2 x 10(9) cells/l) during transport. No significant variation in the proliferation response was seen in the whole blood cell cultures. The main results were the significant signs of simultaneous activity of both the adrenal cortex and the adrenal medulla during transport. PMID- 8342467 TI - Mesangioproliferative glomerulonephritis in mink with encephalitozoonosis. AB - Renal specimens from 6 mink with encephalitozoonosis were studied by light and electron microscopy and immunohistochemistry. The glomeruli of affected kidneys had a mesangioproliferative glomerulonephritis which was characterized by an increase in mesangial cells and matrix in most glomeruli. Some glomeruli were partially or completely sclerosed. There were protein or granular casts in the cortical and medullary tubules. Interstitial nephritis, vasculitis and tubular cysts were found. Electron microscopy demonstrated extensive matrix and increased cellularity in the mesangial areas. Glomeruli showed segmentally thickened or wrinkled capillary basement membranes. Electron dense deposits were found in the glomerular basement membranes and mesangium. Peroxidase-anti-peroxidase immunohistochemistry demonstrated that IgG and IgM positive material was present as granular deposits in the glomerular basement membrane and occasionally in the mesangium. PMID- 8342468 TI - Peripartal excretion of Eimeria oocyst by cows on Swedish dairy farms and the age of calves at first excretion. AB - Faecal samples were collected 3 times a week for 6 weeks from 22 paripartal cows and for up to 15 weeks after birth from 27 calves in 3 herds, to determine the numbers of Eimeria oocysts excreted and the age at which the calves first excreted oocysts. Only low numbers of oocysts were excreted by the cows and no oocysts were detected in 93% of the samples. However, half the cows excreted oocysts at least once. The age at which the calves first excreted oocysts ranged from 2.5 to at least 15 weeks, and there was a significant difference between the herds in their mean age at first excretion. Oocysts of Eimeria alabamensis, E. auburnensis, E. bovis and E. ellipsoidalis were found in numbers ranging from 7 to 8450 oocysts per gram faeces. About 50% of the calves excreted oocysts before they were transferred to group pens. The primary source of infection of the calves was probably their penmates or the previous occupants of the pens, and the cows probably played a subsidiary role. PMID- 8342469 TI - Variations during lactation in total and differential leukocyte counts, N-acetyl beta-D-glucosaminidase, antitrypsin and serum albumin in foremilk and residual milk from non-infected quarters in the bovine. AB - Quarter samples of foremilk and residual milk were taken approximately every second week from 2 days post partum (pp) throughout lactation month 9, from 5 dairy cows in their second lactation period. Bacteriologically positive milk samples were excluded. The aim was to study the variation in total and differential leukocyte counts, N-acetyl-beta-D-glucosaminidase (NAGase), antitrypsin (ATR) and serum albumin (BSA) in milk during the lactation period and different stages of oestrous cycle. Also the between milkings variation was studied from lactation month 4 to 9. At 2 days pp, each fraction of milk contained significantly higher numbers of leukocytes and had a higher activity of NAGase and ATR than later in the lactation period. In foremilk the highest content of BSA was also recorded at 2 days pp. From lactation month 2 to 9, stage of lactation had, in general, a slight effect on the variation in the variables measured. The total leukocyte count in residual milk tended to increase as lactation proceeded. The proportion of monocyte-macrophages in foremilk was significantly decreased during the last 4 months. NAGase and BSA in both fractions and ATR in residual milk increased significantly towards the end of the lactation period. From lactation month 4 to 9 the highest recorded ranges of variation between milkings, within quarter and stage of lactation, in the total leukocyte count, proportions of neutrophils, lymphocytes, monocyte-macrophages, NAGase, ATR and BSA in foremilk were 215 x 10(3)/ml, 42%, 34%, 54%, 6.68 units, 0.36 units and 0.14 mg/ml respectively. The corresponding figures in residual milk were higher except for the variation in BSA which was slightly lower in residual milk than in foremilk. In residual milk there was a positive correlation between the proportion of neutrophils and the total leukocyte count, when calculated on data from all cows and the entire experimental period. During the oestrous periods, the proportion of neutrophils in residual milk was higher than during the dioestrous periods. Foremilk and residual milk differed in the total as well as the differential leukocyte counts in all the various stages of lactation, whereas the contents of NAGase, ATR and BSA were equal in both fractions. The exception was 2 days pp when the proportions of lymphocytes were equal in both fractions and BSA-significantly higher in foremilk than in residual milk. PMID- 8342470 TI - Energy metabolism during late gestation and lactation in multiparous sows in relation to backfat thickness and the interval from weaning to first oestrus. AB - Ten crossbred, fourth or fifth parity sows were divided into 2 groups - high (H) and low (L)- according to their backfat thickness 9 days before parturition. Body weight, backfat thickness and litter weight were recorded repeatedly during a 5 week lactation period. The length of the interval from weaning to first oestrus was also noted. All sows were fed a commercial diet (11.9 MJ/kg, 14.5% crude protein). During gestation, daily food intake was 2.2 kg/sow, while during lactation it was 3.0 kg/sow plus 0.4 kg/piglet. Blood samples were drawn on day 9 before parturition and on days 2, 7, 14 and 21 of lactation. The samples were analysed to determine concentrations of glucose, urea nitrogen, creatinine, triglycerides, free fatty acids and beta-hydroxybutyric acid. In both groups, concentrations of free fatty acids and urea nitrogen were low on day 9 before parturition while those of triglycerides were high, indicating anabolism regardless of backfat thickness. During the first week of lactation, concentrations of free fatty acids increased in the H-group but not in the L group, and concentrations of urea nitrogen were higher in the H-group. These differences, together with the greater loss of weight observed in the H-group, indicate that catabolism of maternal fat and protein depots was more pronounced in the H-group than in the L-group during this time. On day 14 of lactation, both groups showed equally low concentrations of free fatty acids, decreasing creatinine concentrations and stable triglyceride and urea nitrogen concentrations. Furthermore, weight loss during the second and third weeks of lactation was low in both groups. These facts, taken together, indicate that the catabolic rate was decreasing in both groups during this period. No differences in return to oestrus interval were noted between the groups. The present study indicates that under a restricted feeding regime the catabolic rate during the first week of lactation is higher in sows with higher backfat thickness in late gestation. As lactation progresses, a more balanced metabolism is achieved regardless of backfat thickness, which may tend to reduce differences in return to oestrous interval. PMID- 8342471 TI - Patterns of plasma oestradiol-17 beta in relation to the interval from weaning to oestrus in sows. PMID- 8342472 TI - A case of bovine spongiform encephalopathy in Denmark. PMID- 8342473 TI - Disseminated gonococcal infection vs. meningococcal infection. PMID- 8342474 TI - Difficult doctor-patient relationships. PMID- 8342475 TI - How to avoid decortication in childhood empyema. PMID- 8342476 TI - Getting more out of athletic examinations. PMID- 8342477 TI - Oral cancer screening in the elderly. PMID- 8342478 TI - Diary from a week in practice. PMID- 8342479 TI - Superficial tinea infections. AB - Dermatophytes commonly cause superficial dermatoses, especially in children, but these infections are frequently misdiagnosed as nonfungal disease. Superficial tinea infections can vary widely in appearance, ranging from a single, small, circular lesion with mild erythema and a scaling active border to multiple large areas of marked inflammation with vesicle formation. Therefore, laboratory tests, particularly the potassium hydroxide slide preparation, are often necessary to establish the diagnosis. The culture becomes particularly important if the smear is negative but a superficial dermatosis is strongly suspected. Tinea capitis is frequently diagnosed only by culture. Since many agents are available to treat superficial dermatoses, cost should be an important consideration in the selection of a topical antifungal agent. Oral agents are recommended for scalp and nail infections, as well as extensive body infections. Griseofulvin is the oral agent of choice because of its efficacy and low toxicity. PMID- 8342480 TI - Neuroimaging evaluation in multiple sclerosis. AB - Although clinical evaluation remains the cornerstone in the diagnosis of multiple sclerosis, magnetic resonance imaging (MRI) has emerged as the ancillary study of choice. An important diagnostic tool, MRI can also be used to assess disease load, activity and progression, and distinguish between acute and chronic lesions. As technology advances, it will play an essential role in monitoring disease progression and assessing the results of therapy. PMID- 8342481 TI - Tennis elbow. AB - The term "tennis elbow" usually refers to lateral epicondylitis, but the same symptoms can be caused by pathologic processes in the elbow. In fact, most cases of this common condition are caused by occupational stress rather than racket sports. Patients complain of elbow pain when the wrist is extended against resistance or during repetitive actions with the wrist and elbow extended. The condition is thought to be caused by a lesion at the origin of the common wrist extensor mechanism, at or very near the lateral epicondyle of the humerus. Differential diagnosis includes inflammatory, arthritic and nerve entrapment syndromes. Prompt conservative treatment has a high success rate. Patient education, use of a tennis-elbow band and physical therapy play key roles in the management of acute symptoms and in the prevention of recurrence. Surgical intervention is required only when other treatment fails. PMID- 8342482 TI - Sertraline: a new antidepressant. AB - Sertraline is a serotonin reuptake inhibitor that has been approved for use in the treatment of depression. Its side-effect profile is similar to that of fluoxetine, a drug of the same class. The side effects of these drugs most often affect the gastrointestinal tract. Serotonin reuptake inhibitors are nonsedating and free of cardiac effects; they do not cause hypotension, urinary retention or blurred vision. Sertraline, like fluoxetine, appears to be safer than tricyclic antidepressants in overdose. However, no clinical studies comparing sertraline and fluoxetine have been published. The wholesale cost of a month's supply of sertraline is about $50, compared with about $5 for a generic tricyclic antidepressant. Despite their cost, serotonin uptake inhibitors may be the initial drugs of choice in depressed elderly patients, because these patients are at increased risk for suicide and have a low tolerance for the side effects of tricyclic antidepressants. PMID- 8342483 TI - AIDS survival time has nearly doubled since 1984. PMID- 8342484 TI - HIV infection rate remains high in young homosexuals. PMID- 8342485 TI - Maternal cocaine use harms infants more than HIV infection. PMID- 8342487 TI - AAP statement on adolescents and HIV. American Academy of Pediatrics. PMID- 8342486 TI - ACIP issues recommendations for vaccines and immune globulins in immunocompromised persons. Advisory Committee on Immunization Practices. PMID- 8342488 TI - Reimbursement for outpatient biotech drugs, Part 1. PMID- 8342489 TI - Errors caused by medical office personnel. PMID- 8342490 TI - Are chemical sunscreens beneficial for lupus patients who experience photosensitivity? PMID- 8342491 TI - Can nitric oxide be used to treat impotence? PMID- 8342492 TI - New guidelines for managing hypercholesterolemia. National Cholesterol Education Program. PMID- 8342494 TI - Make patients equal partners in health care. PMID- 8342493 TI - An evaluation of cholesterol screening in community pharmacies. PMID- 8342495 TI - Medication errors. PMID- 8342496 TI - Drug abuse is learned behavior. PMID- 8342497 TI - National health care. PMID- 8342498 TI - Quebec turnaround. PMID- 8342499 TI - Pharmacy-based therapeutic drug monitoring. PMID- 8342500 TI - Differences in prevalence and extent of coronary artery calcium detected by ultrafast computed tomography in asymptomatic men and women. AB - Coronary artery calcium is a marker of atherosclerosis in asymptomatic subjects. Ultrafast computed tomography (CT) can detect and quantify coronary calcium, simply and noninvasively, with greater sensitivity than can other techniques. The prevalence and extent of coronary calcium in a large population of asymptomatic men and women were measured and compared. Coronary calcium studies were performed in an asymptomatic population of 1,396 male and 502 female subjects (age range 14 to 88 years). The prevalence of calcium, and the distribution of total calcium scores (which reflect the amount of calcium present) were determined and compared for men and women at 5- and 10-year intervals. The prevalence of calcium in women was half that of men, until the age of 60 years when the difference diminished. The mean total calcium score distributions of men between the ages of 40 and 69 years were virtually identical to those of women between the ages of 50 and 79. The quantitative data obtained by Ultrafast CT showed very close agreement with autopsy studies of coronary calcium. Ultrafast CT is a sensitive technique to measure coronary calcium in both men and women. The differences in prevalence and extent of coronary calcium appear to be parallel to those observed in the clinical incidence of coronary artery disease in men and women. Ultrafast CT may have a greater impact on the treatment of women than of men, because it can be used to provide objective evidence of coronary atherosclerosis. PMID- 8342501 TI - Prognostic value of plasma atrial natriuretic factor, norepinephrine and epinephrine in acute myocardial infarction. AB - Neurohumoral activation in acute myocardial infarction (AMI) may reflect the degree of hemodynamic compromise, contribute to the progression of heart failure and augment to the risk of serious ventricular arrhythmias. Consequently, assessment of neurohumoral variables may provide an index of prognostic value in AMI. Plasma levels of atrial natriuretic factor (ANF), norepinephrine and epinephrine were determined in 145 patients on day 3 after AMI. During the 360 day follow-up period 17 patients died. In univariate analysis, all 3 neurohormones were significantly related to 1-year mortality rates (ANF, p < 0.001; norepinephrine, p = 0.009; epinephrine, p = 0.048). After correction for age, sex, anamnestic, biochemical and clinical variables including signs of clinical heart failure in a multivariate model, ANF remained independently related to mortality. The association between plasma norepinephrine and survival failed to reach statistical significance after introduction of clinical heart failure in the model. Comparison of patients subdivided according to median hormone levels (ANF, 30.3 pmol/liter; norepinephrine, 2.29 nmol/liter) demonstrated a significantly increased mortality rate in patients with elevated ANF (p < 0.001), but not elevated norepinephrine levels. These results suggest that early plasma ANF levels are related to survival in patients with AMI, independently of signs of clinical heart failure. PMID- 8342502 TI - Noninvasive computerized assessment of left ventricular performance and systemic hemodynamics by study of aortic root pressure and flow estimates in healthy men, and men with acute and healed myocardial infarction. AB - Aortic root pressure and flow data can be used to assess left ventricular (LV) performance and properties of the systemic arterial tree. The calibrated subclavian arterial pulse trace was combined with echocardiographic imaging and Doppler velocity recordings to obtain noninvasive estimates of aortic root pressure and flow in 8 healthy subjects (group A), 12 patients with recent myocardial infarction (group B), and 8 with healed myocardial infarction and a dilated left ventricle (group C). The pressure and flow data were transferred to a computer and processed in specially designed software, including a new procedure for estimation of 3-element windkessel model parameters. There were no significant group differences for either aortic root pressure estimates or heart rate. In groups B and C, stroke and cardiac indexes were lower and total peripheral resistance higher than in group A. There were no group differences in the model estimates of total arterial compliance, whereas the characteristic impedance was greater in group C than in A, indicating a less compliant aorta in C. Both LV total and steady power were less in groups B and C than in A, whereas no group difference was found for percent oscillatory power. The reproducibility for recording was good for the aortic root pressure estimates, and lower for the derived parameters (stroke and cardiac indexes, windkessel model parameters and LV power), whereas that for interpretation was generally good. This method provides a unique noninvasive access to important parameters of LV function and the systemic circulation. PMID- 8342503 TI - Wall motion asynchrony is a major determinant of impaired left ventricular filling in patients with healed myocardial infarction. AB - Left ventricular (LV) diastolic filling is impaired in hearts with healed myocardial infarction. Possible hemodynamic parameters related to impaired LV filling include left atrial pressure, time constant of isovolumic relaxation, chamber stiffness and wall motion asynchrony. Previous studies demonstrated univariate correlations between each of these parameters and LV filling. The current study was designed to compare relative importance of these parameters in patients with a myocardial infarction. Left ventriculograms with simultaneous LV pressure measurement were analyzed in 15 patients with a myocardial infarction and in 10 control subjects. Every frame of the left ventriculogram was divided into 8 segments and the volume of each segment was obtained frame-by-frame by planimetry and area-length method. Asynchrony was quantitated as the sum of areas of discrepancy between each segmental and global volume-time curve. Patients with myocardial infarction had greater asynchrony (20 +/- 2 vs 10 +/- 1%, p < 0.01), greater atrial filling fraction (46 +/- 4 vs 35 +/- 5%, p < 0.05) and slower peak early filling rate (2.5 +/- 0.1 vs 4.1 +/- 0.4 end-diastolic volume/s, p < 0.01) than the control subjects. Multiple regression analyses with hemodynamic variables (asynchrony, LV pressure at mitral valve opening, time constant of LV isovolumic pressure decrease and LV chamber stiffness constant) showed that asynchrony and LV pressure at mitral valve opening were significant determinants of LV filling in patients with myocardial infarction, whereas LV pressure at mitral valve opening was the only significant determinant in control subjects. PMID- 8342504 TI - Quantitative severity of stress thallium-201 myocardial perfusion single-photon emission computed tomography defects in one-vessel coronary artery disease. AB - The relation between the quantitative myocardial perfusion defect severity of exercise thallium-201 single-photon emission computed tomography (SPECT) and the quantitative degree of coronary stenosis was examined in 18 patients with 1 vessel disease (> or = 50% diameter stenosis), and abnormal thallium-201 SPECT. A total of 26 vessels were analyzed. Thallium-201 SPECT quantitative defect severity score was derived by summing the number of pixels in a coronary territory in which counts fell below the normal mean and multiplied by the number of SDs by which they fell below the normal mean. The thallium-201 defect severity score was significantly (p < 0.001) related to the maximal percent luminal diameter narrowing (r = 0.93), percent area narrowing (r = 0.89), absolute stenotic area (r = 0.79), and absolute stenotic diameter (r = 0.81). As expected, the strongest relation between thallium-201 defect severity and quantitative angiographic indexes was in the low and high ranges of coronary stenosis, with more variability and lower correlation coefficients (percent diameter: r = 0.75, p < 0.02, percent area stenosis: r = 0.63, p < 0.05) in the middle ranges (50 to 80% diameter stenosis). This observation is likely to be due to the complex flow characteristics across stenotic lesions. The findings suggest that in a select population, thallium-201 defect severity is potentially useful for noninvasive characterization of the functional severity of coronary artery stenosis and may complement coronary angiography in predicting functionally significant stenosis. PMID- 8342505 TI - Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study). The CASCADE Investigators. AB - The Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) study evaluated antiarrhythmic drug treatment of survivors of out-of hospital ventricular fibrillation (VF) not associated with a Q-wave myocardial infarction who were at especially high risk of recurrence of VF. Therapy was randomized to empiric treatment with amiodarone versus treatment with other antiarrhythmic drugs guided by electrophysiologic testing, Holter recording, or both (conventional therapy). The primary end points of the study were cardiac mortality, resuscitated cardiac arrest due to documented VF, or complete syncope followed by a shock from an implanted automatic defibrillator. Two hundred twenty eight patients were enrolled in the study, and baseline characteristics were similar in the patients treated with amiodarone and with conventional therapy. Two hundred two patients (89%) were men with an average age of 62 years. Coronary artery disease was the most common underlying condition (188 of 228, 82%), and in coronary patients, 153 of 188 (81%) had experienced a prior myocardial infarction before the index VF event. Mean left ventricular ejection fraction was 0.35, and 102 patients (45%) had a prior history of congestive heart failure. Survival free of cardiac death, resuscitated VF, or syncopal defibrillator shock for the entire population was 75% at 2 years (amiodarone, 82%; conventional, 69%), 59% at 4 years (amiodarone, 66%; conventional, 52%), and 46% at 6 years (amiodarone, 53%; conventional, 40%); p = 0.007. The survival free of cardiac death and sustained ventricular arrhythmias was 65% at 2 years (amiodarone, 78%; conventional, 52%), 43% at 4 years (amiodarone, 52%; conventional, 36%), and 30% at 6 years (amiodarone, 41%; conventional, 20%); p < 0.001. PMID- 8342506 TI - Noninvasive prediction of efficacy of type IA antiarrhythmic drugs by the signal averaged electrocardiogram in patients with coronary artery disease and sustained ventricular tachycardia. AB - This study attempted to determine if specific changes on the signal-averaged electrocardiogram (ECG) after type IA antiarrhythmic therapy are predictive of efficacy in the treatment of ventricular tachycardia (VT). Scalar and signal averaged ECGs were obtained at baseline and after type IA drug therapy in 15 patients with coronary artery disease and inducible VT at baseline electrophysiologic testing. Signal-averaged QRS duration, root-mean-square amplitude in the last 40 ms of signal-averaged QRS, and the duration under 40 mu v of the signal-averaged QRS (low-amplitude signal), as well as ventricular effective refractory period at electrophysiologic study, and QTc on the scalar ECG were compared. At drug study, 6 patients (group A) had persistent but slower VT, whereas 9 (group B) had VT rendered noninducible. The baseline signal averaged QRS duration was longer in group A than in B (136 +/- 10 vs 115 +/- 13 ms; p < 0.05), as was the scalar QRS (115 +/- 19 vs 98 +/- 11 ms; p < 0.05). After antiarrhythmic therapy, group A had a greater prolongation of both signal averaged QRS (24 +/- 10 vs 8 +/- 3 ms; p < 0.05) and low-amplitude signal (31 +/- 13 vs 3 +/- 7 ms; p < 0.05), whereas group B had a greater increase in ventricular effective refractory period (49 +/- 20 vs 20 +/- 13 ms; p < 0.05) and corrected QT interval (100 +/- 39 vs 43 +/- 23 ms; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342507 TI - Usefulness of propafenone for supraventricular arrhythmias in infants and children. AB - The relation between propafenone dose, serum level, electrocardiographic parameters, antiarrhythmic drug efficacy and adverse effects was studied in 47 children with symptomatic supraventricular arrhythmias aged 1 day to 10.3 years (median 2.2 months) with a mean follow-up of 14.3 months. Propafenone trough serum levels were measured using gas chromatography. Oral propafenone (mean dose 353 mg/m2/day) was effective in 41 of the 47 patients (87.2%). Serum levels did not differ between patients responding and not responding to propafenone (0.45 +/ 0.40 vs 0.36 +/- 0.41 mg/liter). PR interval and QRS complex duration increased more significantly with propafenone dose increments (p < 0.001), than with propafenone serum levels (p < 0.05). At successful treatment PR interval and QRS complex were prolonged by a mean of 19.2 and 20.5% compared with pretreatment status. Five patients exhibited unexpected marked QRS complex prolongation (50 to 200%) despite low propafenone dosage (< 300 mg/m2/day) and level ranging from 0.05 to 1.33 mg/liter. Three patients (6.1%) were suspected of being "poor" metabolizers of propafenone. Mild chronic elevation of serum liver enzymes was observed in 5 patients treated with a larger dose (mean 448 mg/m2/day, p < 0.001). No proarrhythmia was noted on serial Holter monitors. One patient with Wolff-Parkinson-White syndrome and a normal heart had cardiac arrest after aspiration. Serial monitoring of PR interval and QRS complex duration was more useful for proper dosage adjustment than propafenone serum levels. Serum liver enzymes should be closely monitored when using higher propafenone doses. Malignant proarrhythmia could not be excluded in the 1 patient with cardiac arrest. PMID- 8342508 TI - Experience with three different third-generation cardioverter-defibrillators in patients with coronary artery disease or cardiomyopathy. AB - Clinical investigations are being performed in multiprogrammable devices whose therapeutic options include antitachycardia pacing, cardioversion, defibrillation and bradycardia pacing. Three different third-generation devices were implanted in 46 research patients at 1 clinical center to document their safety and efficacy for the treatment of malignant ventricular arrhythmias. Additionally, the purpose of the study was to determine if antitachycardia pacing is a desirable and frequently used feature of tiered devices. The Medtronic PCD was implanted in 15 patients (12 men, mean age 60 +/- 13 years, mean ejection fraction 40 +/- 15%), the Ventritex Cadence in 21 patients (17 men, mean age 65 +/- 10 years, mean ejection fraction 38 +/- 12%), and the CPI VENTAK PRx in 10 patients (8 men, mean age 63 +/- 14 years, mean ejection fraction 31 +/- 8%). All patients presented with cardiac arrest or ventricular tachycardia. During follow up of 10 +/- 6 months (range 1 to 19), 70% of the 20 patients with antitachycardia pacing activated used the feature for spontaneous ventricular tachycardia. The antitachycardia pacing parameters were reprogrammed 20 times in 15 patients. Two thousand six hundred thirty-eight of 2,675 (98%) antitachycardia pacing attempts successfully terminated spontaneous tachyarrhythmias. Low-energy cardioversion or defibrillation terminated tachyarrhythmias in patients where pacing was unsuccessful. One hundred forty-eight episodes of tachycardia were successfully treated directly by shocks in 16 of 46 patients (35%). There were no deaths due to device failure. This initial single-center clinical experience suggests that the PCD, Cadence and VENTAK PRx are all safe and effective tiered therapy devices for the treatment of malignant ventricular arrhythmias. Antitachycardia pacing successfully terminated most episodes of ventricular tachycardia; in patients with this feature activated, it was used frequently but required reprogramming to achieve high levels of success. PMID- 8342509 TI - Information on type 1 diabetes mellitus and QT interval from identical twins. AB - To determine whether QT interval is influenced by genetic factors and whether QT interval prolongation occurs in type 1 diabetes or is related to diabetic autonomic neuropathy, QT intervals were measured, and autonomic function was assessed in 44 pairs of identical twins who were discordant for type 1 diabetes. Twins were compared with 44 normal control subjects of similar age and sex. QT intervals were corrected for heart rate (QTc). QTc in diabetic twins correlated with that in their nondiabetic co-twins (r = 0.41; p = 0.006). Diabetic twins had significantly longer QTc than did their nondiabetic co-twins and control subjects (416 +/- 18 vs 407 +/- 16 and 403 +/- 19 ms, respectively; p < 0.005). A greater number of abnormal autonomic function tests were detected in diabetic twins than in their nondiabetic co-twins and control subjects (8 vs 2 and 0%, respectively; p < 0.01). Diabetic twins with disease duration > 14 years (n = 22) had longer QTc than did their nondiabetic co-twins (420 +/- 17 vs 402 +/- 14 ms; p < 0.0005). Twins with diabetes for > 14 years had a greater frequency of abnormal autonomic function tests than did those with diabetes < 14 years (15 vs 2%; p < 0.001). QTc did not correlate with autonomic function in diabetic twins. It is concluded that QT interval is influenced by genetic factors, and in type 1 diabetes, QTc can be prolonged independently of autonomic neuropathy. PMID- 8342510 TI - Sex differences in cardiac adaptation to isolated systolic hypertension. AB - This study examines the association of isolated systolic hypertension with left ventricular (LV) mass and geometry in men and women. The subjects of this study were surviving members of the Framingham Heart Study and the Framingham Offspring Study who attended the index examination (between 1979 and 1983) and were aged > or = 50 years, free of clinically apparent cardiovascular disease, not taking antihypertensive medication and without diastolic hypertension (diastolic blood pressure < 90 mm Hg), and in whom LV mass could be determined by echocardiography. Examinations routinely included 12-lead resting electrocardiography, measurements of resting blood pressure, anthropometry, blood glucose levels, and M-mode echocardiography. M-mode echocardiograms adequate to assess LV hypertrophy were obtained for 1,282 normotensive subjects (538 men and 744 women) and 79 subjects with isolated systolic hypertension (26 men and 53 women). Adjusting for age, body mass index and diastolic blood pressure, the relative odds of LV hypertrophy associated with isolated systolic hypertension were 2.58 (95% confidence interval 0.97 to 6.86) in men and 5.94 (95% confidence interval 3.06 to 11.53) in women. Women with isolated systolic hypertension had increased LV wall thickness and mass without LV chamber enlargement, but men had LV dilation and increased LV mass without increased wall thickness. In conclusion, although isolated systolic hypertension was associated with increased LV mass in men and women, the geometric pattern of increased LV mass differed by sex; although women demonstrated a pattern of concentric hypertrophy, an eccentric pattern was observed in men. PMID- 8342511 TI - Frequency of ring abscess and cuspal infection in active infective endocarditis involving bioprosthetic valves. AB - When active infective endocarditis (IE) involves a bioprosthetic valve, the infective process may involve only the cusps or sewing ring or both. We studied 34 patients with infected bioprostheses to determine whether the infection involved the cusps or ring, or both, because these locations could affect prognosis. In the 5 patients in whom active IE began < 60 days after operation, the infection involved the cusps only in 2, the ring only in 2, and both in 1. The 29 patients in whom signs and symptoms of active IE appeared > 60 days after valve replacement were subdivided into 3 categories based on the valve or valves replaced. In the 16 patients with isolated aortic valve replacement, the infection involved the cusps only in 6, the ring only in 4, and both in 6. In the 6 patients with isolated mitral valve replacement, the infection involved the cusps only in 2, the ring only in 1, and both in 3. In the remaining 7 patients, 15 native valves were replaced with bioprostheses, and 10 of them were infected. The infection involved the cusps only in 7, and both the cusps and ring in 3. Of all 34 patients, 13 had operative excision of the infected bioprosthesis: 1 died within 60 days of the bioprosthetic excision, and 1 was lost to follow-up; of the remaining 11 patients, 4 died late (1.5, 3, 5 and 14 years), and the other 7 are alive 5 to 10 years after bioprosthetic excision (all in New York Heart Association functional class I or II). Thus, although infection limited to the bioprosthetic cusps may reasonably allow a better outlook, reoperation with infection involving the annular ring (8 of 13 reoperation patients) does not prevent successful outcome. PMID- 8342512 TI - Percutaneous mitral valvuloplasty with severe pulmonary artery hypertension. AB - The aim of this study was to assess the initial and midterm outcome of patients with severe pulmonary hypertension undergoing percutaneous mitral valvuloplasty (PMV). Accordingly, the baseline characteristics, immediate results and follow-up of 64 consecutive patients with severe pulmonary artery hypertension (systolic pulmonary artery pressure > or = 60 mm Hg on cardiac catheterization) (group I) were analyzed and compared with those of 194 consecutive patients with lower pulmonary pressures (group II). Patients in group I were more symptomatic (New York Heart Association functional class > or = III, 72 vs 40%, p < 0.001) and had higher echocardiographic scores (8.6 +/- 2 vs 7.4 +/- 1, p < 0.05). Before PMV, mitral gradient was higher (17 +/- 6 vs 13 +/- 5 mm Hg, p < 0.025) and mitral valve area smaller (0.79 +/- 0.2 vs 0.96 +/- 0.2 cm2, p < 0.005) in group I patients, who also had higher pulmonary vascular resistances (469 +/- 299 vs 157 +/- 125 dynes s-1 cm-5, p < 0.005). On multivariate analysis patients in group I were more symptomatic, had smaller mitral valve areas and higher mitral gradients. PMV success (area gain > 50% without complications) was similar (89 vs 87%) in both groups. After PMV final mitral gradient (5 +/- 2 vs 4 +/- 2 mm Hg) and area (1.82 +/- 0.5 vs 1.87 +/- 0.5 cm2) were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342513 TI - Effects of serotonin on coronary arteries of cardiac transplant recipients. AB - Serotonin constricts coronary arteries with endothelial dysfunction. To detect early graft artery disease, the responses to intracoronary serotonin were studied 1 month (group A, 14 patients) and 1 year (group B, 13 patients) after orthotopic cardiac transplantation. No patient had evidence of rejection and all had angiographically normal coronary arteries. Serotonin in increasing doses (1, 10 and 20 micrograms/min for 2.5 minutes each) was infused into the coronary circulation. Diameters of proximal, middle and distal segments were measured by quantitative angiography. At the maximal concentration of serotonin, the diameters of the proximal segments decreased to 73 +/- 4% (percentage of the baseline) in group A; the diameters of the middle and distal segments decreased to 67 +/- 5 and 63 +/- 4%, whereas in group B, the diameters of the proximal, middle and distal segments were 90 +/- 6% (p < 0.02 vs group A value), 88 +/- 5% (p < 0.01 vs group A value) and 84 +/- 4% (p < 0.01 vs group A value), respectively. These changes were significantly (p < 0.02) different from those observed in 6 control patients in whom no constriction was induced by intracoronary serotonin. Moreover, coronary plasma endothelin levels were significantly higher in group A than in group B and control patients (5.6 +/- 0.3 vs 4.3 +/- 0.2 fmol/ml in group B and 3.9 +/- 0.3 fmol/ml in control patients). Thus, an abnormal response to intracoronary serotonin seems to occur often in transplant patients, and this abnormality is unexpectedly more pronounced in the early weeks after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342514 TI - Spa therapy for heart disease Bad Nauheim (circa 1900). AB - The development of Bad Nauheim, a German spa that over 2 centuries became dominant in the attraction of patients with heart disease is described. Here, patients experienced a regimen of saline baths and mostly static exercises developed by the Schotts, 2 physician brothers. Concomitant with the bathing and exercises, there was a social atmosphere conducive to relaxation. Many visiting physicians were impressed that there were improvements in the patients' cardiac status. One skeptical exception was Sir James Mackenzie, whose views are synopsized. The reported improvements may have had a modicum of a physiologic base, from recent investigations on the nature of heart failure, and may have anticipated the current use of exercise in cardiac rehabilitation. PMID- 8342515 TI - The paradox of nitrates in patients with angina pectoris and angiographically normal coronary arteries. PMID- 8342516 TI - Serum ferritin is not a risk factor for coronary artery disease in men and women aged > or = 62 years. PMID- 8342517 TI - Value of clinical variables for risk stratification in patients with sustained ventricular tachycardia and history of myocardial infarction. PMID- 8342518 TI - Impact of directional atherectomy on adjacent branch vessels. PMID- 8342519 TI - Catheter creation of an open outflow tract in previously atretic right ventricular outflow tract associated with ventricular septal defect. PMID- 8342520 TI - Quantitation of left ventricular volumes and ejection fraction by biplane transesophageal echocardiography. PMID- 8342521 TI - On-line quantification of left ventricular function by automatic boundary detection and ultrasonic backscatter imaging. PMID- 8342522 TI - Both aborted sudden cardiac death and end-stage phase in hypertrophic cardiomyopathy. PMID- 8342524 TI - Sudden death, right ventricular infarction, and abnormal right ventricular intramural coronary arteries in isolated congenital valvular pulmonic stenosis. PMID- 8342523 TI - Congestive heart failure, dilated cardiac ventricles, and sudden death in hyperthyroidism. PMID- 8342525 TI - Triglycerides, high-density lipoproteins and the Framingham Heart Study. PMID- 8342526 TI - Are autopsies still useful? Thank goodness we didn't know. Not all tumors are bad tumors. Most of the cavity has to be filled before trouble occurs. PMID- 8342527 TI - Great expectations and disappointment with laser angioplasty. PMID- 8342528 TI - Accuracy of recall of hip fracture, heart attack, and cancer: a comparison of postal survey data and medical records. AB - Accuracy of recall of hip fracture, heart attack, and cancer was evaluated by comparing data obtained from postal surveys and medical records of participants in the Leisure World Disease Prevention Study. The study cohort comprised 13,897 residents of Leisure World Laguna Hills who responded to a questionnaire first mailed in 1981. Follow-up questionnaires requesting information on recent disease history were mailed in 1983 and 1985 to all living cohort members and were returned by 9,734 (86%) and 8,884 (82%) persons, respectively. The proportion of false-positive answers was about 40% for acute myocardial infarction, but less than 10% for hip fracture and cancer. Many of those who gave a false-positive answer on the questionnaire had a condition that the lay population might easily confuse with the condition of interest (e.g., heart attack vs. other cardiovascular disease). Among persons with the disease of interest recorded in the medical record, the percentage who failed to report their events on the questionnaires was highest for those who had an acute myocardial infarction, followed by those who had cancer and those who had hip fracture. The highest rates of confirmation of cancer were for cancers of the breast, bladder, prostate, and uterus. For closely related sites (e.g., colon and rectum), the reliability of reports decreased. The amount of information obtained varied according to the wording of the questionnaire and the specificity of the questions asked. Improved accuracy of recall was observed when the occurrence of specific diseases was asked in addition to a general question about recent hospitalizations. PMID- 8342529 TI - Past and recent physical activity and risk of hip fracture. AB - A population-based case-control study was conducted to examine the effects of past and recent physical activity on the risk of hip fracture in women. Cases included females aged 55-84 years with a first diagnosis of hip fracture in 1989 in metropolitan Toronto, Canada. Controls were a population-based random sample frequency matched by 5-year age groups. Data were collected on 381 cases and 1,138 controls by self-administered mailed questionnaires or telephone interviews. Past activity was calculated as a compilation of activity scores at ages 16, 30, and 50 years. Recent activity was defined as activity in the past year for controls and activity in the year before fracture for cases. Multiple logistic regression was used to control for age, previous fracture, obesity, smoking, osteoporosis, epilepsy, stroke or Parkinson's disease, daily intake of dietary calcium, and duration of use of supplemental calcium, fluoride, and estrogen. After recent activity was adjusted for, statistically significant effects were found for women who in the past had been active (odds ratio estimate (OR) = 0.66, 95% confidence interval (CI) 0.45-0.96) or very active (OR = 0.54, 95% CI 0.33-0.88). After past activity was adjusted for, a similar protective effect was found for women who were moderately active recently (OR = 0.61, 95% CI 0.41-0.90), but women who were very active recently were not protected from hip fracture (OR = 1.15, 95% CI 0.72-1.83). This study showed evidence of independent protective effects of past physical activity and of moderate levels of recent physical activity on the risk of hip fracture in postmenopausal women. PMID- 8342530 TI - Variations in the accuracy of obstetric procedures and diagnoses on birth records in Washington State, 1989. AB - The authors abstracted a sample of 7,536 hospital medical records to validate the accuracy of the coding of obstetric information on 1) birth certificates, 2) a statewide computerized hospital discharge abstract data system, and 3) a linked file merging birth certificates and the hospital abstract data for Washington State deliveries occurring in 1989. Measures of accuracy of coding of delivery method and obstetric procedures varied greatly among the 23 hospitals that participated in the study. Computerized hospital discharge data were generally more complete and accurate than were birth certificate data. The linked file was more likely to identify obstetric procedures than was either source alone. For example, only 84.1% of cesarean deliveries noted in the hospital charts were identified on birth certificates (range among hospitals, 37-100%). Using the linked file, the authors identified 99.8% of cesarean deliveries (range, 97 100%). Linked birth certificate-hospital abstract files may become an excellent source of data for epidemiologic and health care studies; however, further training of medical record personnel and standardization of coding are needed to improve the quality of computerized data on obstetric events. PMID- 8342531 TI - Risk attribution and tobacco-related deaths. AB - The number of deaths that would not have occurred had an exposure or trait been absent is generally estimated by observing mortality rates in sample populations of exposed and nonexposed persons and applying them to the population of interest. Three methods used to estimate deaths due to tobacco use are evaluated. Each method requires estimates of certain absolute and relative risks, and the published estimates based on them assume that the absolute and relative risks observed in the two large American Cancer Society prospective studies can be applied to the US population or to populations in developed countries. Computations using large representative samples of US decedents and of the entire US population for these methods result in estimated numbers of deaths for the US population that are substantially lower than those based on Cancer Prevention Survey-I or Cancer Prevention Survey-II. Computations also showed that controlling for confounding from two smoking-related variables results in still lower estimates of the number of excess deaths. Consequently, published results that ignore confounding and are based on nonrepresentative data overstate the contribution of smoking. It is imperative that estimates of excess deaths be based on representative data and control for relevant confounders. PMID- 8342532 TI - Relation between anthropometric indicators and risk of breast cancer among Australian women. AB - Associations between various anthropometric indicators and breast cancer were investigated in a community-based case-control study conducted among 456 premenopausal women (135 cases) and 656 women who were at least 10 years past menopause (185 cases) in Brisbane, Australia, from 1981 to 1985. Among postmenopausal women, increased risk was associated with greater weight at age 25 years (p trend = 0.002) and with a heavier maximum weight (p trend = 0.003), but not with recent weight. Results were similar for relative weight (weight (kg)/height (m)1.5). Overall, weight gain was unrelated to the occurrence of breast cancer, although risks were elevated among postmenopausal women who weighed less at age 25 (< 54 kg) and subsequently experienced a large weight gain (> 13 kg). Among premenopausal women, there was little indication that body size or change in weight was related to breast cancer. These results suggest that both heaviness in early adulthood and a large maximum weight at any time are associated with elevated risks for postmenopausal breast cancer. PMID- 8342533 TI - Is ovarian cancer associated with an increased frequency of germinal inclusion cysts? AB - It has been proposed that epithelial ovarian cancers arise in germinal inclusion cysts of the ovary, which are thought to form as stigmata of ovulation. To evaluate whether the frequency of germinal inclusion cysts is associated with ovarian cancer, the authors counted the germinal inclusion cysts in single slides of sections from ovaries of 148 women who underwent incidental oophorectomy and from the contralateral ovaries of 37 women with unilateral ovarian cancer at Columbia-Presbyterian Medical Center, New York, New York, in 1985-1991. The mean number of germinal inclusion cysts was 2.7 for cases and 3.6 for controls. Conditional logistic regression analysis showed that germinal inclusion cysts were not associated with ovarian cancer (odds ratio = 0.98, 95% confidence interval 0.92-1.04). These findings do not support the hypothesis that increased formation of inclusion cysts is a risk factor for ovarian cancer. PMID- 8342534 TI - Relation of caffeine intake to blood lipids in elderly women. AB - The relation of the consumption of caffeine from coffee, tea, and all caffeine containing soft drinks (hereafter referred to as "cola") to blood lipid levels was studied in 1,035 white women ranging in age from 65 to 90 years (mean, 71.2 years) from October 1986 through October 1988. All study subjects were participants in the Pittsburgh, Pennsylvania, clinic of the Study of Osteoporotic Fractures. Fasting blood samples were tested for total cholesterol, triglycerides, apolipoproteins A-I and B-100, total high-density lipoprotein (HDL) cholesterol, and the HDL2 and HDL3 subfractions. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. Current consumption of coffee, tea, and cola was assessed by means of a self-administered personal habits questionnaire. Potential confounders, such as body mass index (weight (kg)/height (m)2), waist/hip ratio, smoking status, and alcohol intake were also measured for each woman. Analyses of variance and tests for mean differences revealed an inverse relation between the consumption of tea and apolipoprotein B-100 and a positive association between the consumption of cola and apolipoprotein B-100. Apolipoprotein A-I levels were found to be positively related to coffee consumption and negatively related to tea consumption. There was no consistent relation between caffeine consumption and total cholesterol, LDL cholesterol, total HDL cholesterol and its subfractions, or apolipoprotein B 100. Adjustment for potential confounders yielded no remaining significant associations between caffeine from any of the major beverage sources and any of the lipid fractions. In conclusion, the inconsistent relations between caffeine from various sources and blood lipids do not support a significant association of blood lipid levels with caffeine consumption in elderly women. PMID- 8342535 TI - A simple, practical model for reducing alloimmunization in patients with sickle cell disease. AB - Patients with sickle cell disease (SCD) form immune alloantibodies more frequently than other transfused populations because red cells (RBCs) from white donors (with a higher incidence of certain Rh, Duffy, Kell, and Kidd blood group antigens) are transfused to black patients often lacking these antigens. We propose a model to reduce alloimmunization in patients with SCD by providing them with blood from only black random donors. Rationale is shown by examining calculations based on the phenotype E-, C-, Fy(a-), K-, and Jk(b-). There is a 7% probability that this phenotype belongs to a white donor, while there is a 93% probability that this phenotype belongs to a black donor. The probability of selecting blood from a black donor identical with the above phenotype for black recipients from an all black population and from a typical urban blood inventory population (90% white, 10% black) is 1/4 and 1/33, respectively. Therefore, an 8 fold greater chance of selecting antigen non-identical blood occurs if blood is obtained from a typical urban donor population as compared to a black population. Based on these calculations, alloimmunization can be reduced prospectively in patients with SCD by meeting their transfusion requirements with blood selected from random black blood donors. PMID- 8342536 TI - Comparison of buffy coat preparation to direct method for the evaluation and interpretation of bone marrow aspirates. AB - Bone marrow differential and French, American, British (FAB) classification of buffy coat preparation (BCP) was compared to direct method (DM) in 69 pediatric patients with various hematologic and oncologic disorders. The marrow evaluation differed significantly in 12 of 69 patients (17.4%). The differential counts were discordant in 9 out of 69 patients (13%), and the FAB classifications were discordant in 3 out of 25 patients (12%) with acute lymphoblastic leukemia (ALL). Underestimation of the percent blasts occurred with buffy coat preparation in patients with acute non-lymphoblastic leukemia (ANLL). While buffy coat preparations can facilitate morphologic evaluation in marrow malignancies, significant errors can occur in determination of the differential count. Direct smear should be used in conjunction with buffy coat smears in the evaluation of bone marrow aspirates. PMID- 8342537 TI - DNA diagnosis for the detection of sickle hemoglobinopathies. AB - At this time, the sole generally accepted use for DNA diagnosis in the hemoglobinopathies is for the prenatal detection of disease, which can be identified by these means early in the first trimester of pregnancy. By ascertaining genotype rather than phenotype, the confusion that results from diagnostic errors should be diminished. DNA diagnostics are the future of all genetic disease detection and this future will soon be upon us. PMID- 8342538 TI - Lymphoproliferative disease of "LAK cell" precursor large granular lymphocytes in association with celiac disease. AB - We have investigated a case of lymphoproliferative disease of large granular lymphocytes (LDGL) occurring in association with celiac disease, anemia, neutropenia, and carcinomas of the endometrium, breast, and skin. The large granular lymphocyte (LGL) proliferation was monoclonal, T cell in origin, with T cell receptor beta-chain gene rearrangement, and a CD3+, CD8+, CD16+/- phenotype. In spite of the high frequency of LGL, natural killer (NK) cell activity was absent. Stimulation with interleukin-2 in vitro, however, resulted in high lymphokine-activated killer (LAK) cell activity against NK-resistant targets. The T-cell nature of the LAK precursor cells is in contrast to the majority seen in normal peripheral blood. Therapeutic trials of cyclosporin A, low-dose cyclophosphamide, and levamisole were unsuccessful in reducing transfusion requirements. This case is unique in the association of LDGL with celiac disease. It is also unique in that the patient had been followed for several years prior to the onset of the LDGL. The case extends the list of lymphoproliferative disorders documented to be associated with celiac disease and, conversely, adds to our knowledge of lymphoproliferative disorder of LGL and its "dysimmune" manifestations. PMID- 8342539 TI - Chronic myelogenous leukemia and acute lymphoblastic leukemia occurring in the course of polycythemia vera. AB - We are reporting an unusual case of a 54-year-old woman with polycythemia vera (PV) who developed Ph chromosome positive chronic myelogenous leukemia (CML) 8 years after the initial diagnosis of PV, and terminating in acute lymphoblastic leukemia (ALL), 11 years after the initial diagnosis. Cytogenetic studies revealed a normal female karyotype at the time of diagnosis of PV and the presence of a Ph chromosome at the time of appearance of CML. Southern blot hybridization revealed a bcr rearrangement in both mononuclear cells and granulocytes. The diagnosis of ALL was established on the basis of morphology, positive TdT staining, and monoclonal antibody studies positive for 12, B4, and J5. This case demonstrates the transition of PV into CML, followed by a blastic transformation into acute lymphocytic leukemia. At termination of her disease there were findings compatible with bi-phenotypic leukemia. These findings would suggest that the disease arose in a primitive multipotential stem cell. PMID- 8342540 TI - Reactivation and dissemination of blastomycosis complicating Hodgkin's disease: a case report and review of the literature. AB - Patients presenting with Hodgkin's disease (HD) may show lung involvement characterized by contiguous spread from ipsilateral hilar lymph nodes. Lung consolidation or noncontiguous pulmonary involvement makes an alternative diagnosis more likely. This report describes a patient with HD in whom concurrent pulmonary blastomycosis was recognized only after chemotherapy had started and dissemination had occurred. Although Blastomyces dermatitidis may behave as an opportunist pathogen, there are no previous reports of blastomycosis in patients with HD. Undiagnosed active opportunistic infection at the time of diagnosis of HD may complicate staging as well as treatment. Biopsy of lung lesions with stain and culture for opportunistic pathogens should be considered in patients with newly diagnosed HD disease and atypical patterns of lung involvement. PMID- 8342541 TI - Terminal acute myelogenous leukemia in a patient with congenital agranulocytosis. AB - Congenital agranulocytosis terminating in acute myelogenous leukemia has been previously reported in only two cases of adolescent males. We describe the clinical and laboratory features of a 13-year-old male with congenital agranulocytosis, treated with G-CSF with initial good neutrophil response, who subsequently developed acute myeloid leukemia. This rare complication may define a preleukemic subset of patients for whom G-CSF therapy is ineffective. The diagnostic challenges of this case are presented. PMID- 8342542 TI - A new alpha-thalassemia-2 deletion resulting in microcytosis and hypochromia and in vitro chain imbalance in the heterozygote. AB - We have detected a novel alpha-thalassemia-2 with a large (18+ kb) deletion involving the alpha 1- and theta 1-globin genes and the 3' hypervariable region sequence. Unexpectedly, the heterozygote had a mild anemia with a marked microcytosis and hypochromia, and an in vitro alpha/beta chain synthesis ratio of 0.62-0.66. It is suggested that the deletion includes a sequence that is involved in the in cis regulation of the alpha 2-globin gene. PMID- 8342543 TI - Measurement of beta 2-glycoprotein I (apolipoprotein H)-independent anticardiolipin antibody in human immunodeficiency virus-1-positive and -negative hemophiliacs. AB - The authors studied whether or not anticardiolipin antibody (aCL), which is frequently detected in hemophiliacs with human immunodeficiency virus-1 (HIV-1) infection, is dependent on beta 2-glycoprotein I (GPI), a cofactor of cardiolipin (CL). GPI-independent aCL was positive in 27 of 36 hemophiliacs with HIV-1 antibody (75%) and in 23 of 29 patients without HIV-1 antibody (79%). However, only six HIV-1-positive and four HIV-1-negative patients were positive for GPI dependent aCL. Thus the aCL in these hemophiliacs was GPI independent and therefore different from the aCL found in autoimmune diseases, such as systemic lupus erythematosus. PMID- 8342544 TI - Ultrastructure of neutrophilic phagosome of autologous platelet in vivo in specific granule deficiency. AB - The ultrastructure of neutrophilic phagosomes containing autologous platelets in vivo from a woman with specific granule deficiency is described. This phagosome formation was observed only when she had developed pneumonia due to Staphylococcus aureus. Therefore, the phenomenon might be induced by severe bacterial infection under an abnormal neutrophilic condition accompanied by specific granule deficiency. PMID- 8342545 TI - Treatment options in primary erythermalgia? PMID- 8342546 TI - Treatment of myelofibrosis and primary erythermalgia. PMID- 8342547 TI - Malnutrition is a prognostic factor in childhood lymphoblastic leukemia. PMID- 8342548 TI - B-cell malignancy associated with disseminated herpes simplex and a large granular lymphocyte response. PMID- 8342549 TI - Intraperitoneal chemotherapy with cytosine arabinoside in agnogenic myelofibrosis with myeloid metaplasia and ascites due to peritoneal extramedullary hematopoiesis. PMID- 8342550 TI - Case of Crohn's disease in bone marrow transplantation. PMID- 8342551 TI - Pregnancy-associated factor VIII inhibitor: treatment with intravenous high-dose immunoglobulin. PMID- 8342552 TI - Jehovah's Witnesses and acute leukemia. PMID- 8342553 TI - Ciprofloxacin-induced neutropenia and erythema multiforme. PMID- 8342554 TI - Lymphoma of large granular lymphocytes. PMID- 8342555 TI - Heterogeneous proliferative effect of tumor necrosis factor-alpha and lymphotoxin on mitogen-activated B cells from B-chronic lymphocytic leukemia. AB - The proliferative effect of tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin on B cells from patients with B-chronic lymphocytic leukemia (B-CLL) was studied. Fresh purified B-CLL lymphocytes showed no proliferative response to either recombinant (r) TNF-alpha or r-lymphotoxin. However, after "in vitro" activation of B-CLL lymphocytes for 2 days with Staphylococcus aureus Cowan 1 (SAC), four of seven patients showed enhanced blastogenic response in the presence of either rTNF-alpha or r-lymphotoxin. We also found that the proliferative response of SAC-activated B-CLL lymphocytes to the two cytokines was independent of that found in the presence of interleukin-2. These results demonstrate that TNF-alpha and lymphotoxin can heterogeneously support the proliferation of in vitro activated B cells from B-CLL patients and may reflect the biological heterogeneity of B-CLL disease. PMID- 8342556 TI - Increase of hemoglobin A2 in human immunodeficiency virus-1-infected patients treated with zidovudine. AB - We observed increased hemoglobin A2 (HbA2) levels in an asymptomatic human immunodeficiency virus-1 (HIV1) patient with no previous history of beta thalassemia. He was treated only with zidovudine (AZT). In an attempt to understand this observation, a retrospective study was initiated to determine whether mean HbA2 levels are higher in AZT-treated patients than in subjects not receiving this drug and to assess if other hematologic alterations are associated with elevated HbA2. One hundred fifty-one HIV-positive cases were investigated; AZT was administered to 81 of them. The mean value of HbA2 was 0.032 (SD +/- 0.005) for the treated group vs. 0.027 (SD +/- 0.004) for the controls. This difference was highly significant (P < 0.001). Twenty-four patients (31%) in the treated group had elevated HbA2 levels vs. none in the controls. Bone marrow toxicity seemed to be more significant in patients with heightened HbA2 values, and HbA2 levels did not increase with CDC clinical stage. We conclude that AZT may be linked to high HbA2 levels in some patients. PMID- 8342557 TI - Coagulation system activation and increase of D-dimer levels in peripheral arterial occlusive disease. AB - The aim of the present study was to document coagulation system activation and basal fibrinolysis in peripheral arterial occlusive disease (PAOD) at stage II of Fontaine's classification. In 34 patients, prothrombin fragment (F1 + 2), thrombin-antithrombin III complexes (TAT), and D-dimer concentrations were evaluated before and after a standard treadmill test. Basal levels in PAOD of F1 + 2 (1.25 +/- 0.19 nmol/liter) and of TAT (3.34 +/- 0.35 micrograms/liter) were significantly increased compared to those obtained in age- and sex-matched healthy controls (0.68 +/- 0.06 nmol/liter and 2.30 +/- 0.33 micrograms/liter, respectively), showing baseline activation of the clotting cascade. A secondary activation of the fibrinolytic system was evidenced by the highly significant increase of basal D-dimers (719 +/- 99 ng/dl in PAOD vs. 229 +/- 37 ng/dl in controls). Treadmill exercise failed to increase the study parameters significantly further. Walking distance (583 +/- 40 m) was correlated with the preexercise ankle to brachial systolic blood pressure ratio (r = 0.485, P < 0.005) and inversely with the level of D-dimers (r = -0.425, P < 0.02). Under baseline conditions, the latter parameter was correlated as well with the antigen concentration of urokinase-type plasminogen activator (u-PA; r = 0.503, P < 0.002). These results indicate that stage II PAOD is characterized by an activation of the clotting cascade in baseline conditions evidenced by increased F1 + 2 and TAT. A secondary activation of the fibrinolytic system with increased u-PA antigen levels accounts for the elevated D-dimers. Treadmill exercise was unable to increase these parameters further. PMID- 8342558 TI - Hematologic remission and cytogenetic improvement after treatment of stable-phase chronic myelogenous leukemia with continuous infusion of low-dose cytarabine. AB - Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15-30 mg/m2/day were therefore administered for extended periods to patients with CML in stable phase to determine if this treatment could achieve selective cytoreduction of Philadelphia chromosome (Ph)-positive cells. Five patients demonstrating > 90% Ph-positive metaphases before treatment received a total of 43 cycles of cytarabine infusional therapy. Cytarabine was administered on an outpatient basis using a portable, battery-operated syringe pump until the total leukocyte count reached 2500/microliters or the platelet count reached 75,000/microliters. A new cycle was begun when the total leukocyte count exceeded 4,000/microliters and the platelet count exceeded 100,000/microliters. The median duration of cytarabine administration per cycle was 29 days (range 15-72 days). Leukocytosis was readily controlled by low-dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytarabine therapy. The fraction of Ph-positive metaphases in the marrow of the five patients was reduced to 0, 10%, 43%, 72%, and 84%, respectively, during therapy. The median time to achieve optimal cytogenetic response was 4.8 months (range 2.8-8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Another patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38% Ph-positive marrow metaphases (range 10-53%) over 32 months. Cytarabine therapy was generally well-tolerated, but was discontinued in one patient because of persistent asymptomatic elevations in hepatic enzymes, which resolved within 2 months after discontinuing therapy. There were no episodes of fever during neutropenia, and platelet transfusions were not required. However, symptomatic anemia requiring transfusion of red cells occurred during most cycles of treatment. In summary, treatment of CML with low dose cytarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain the effect of this treatment on duration of stable phase and overall survival. PMID- 8342559 TI - Significant hyponatremia following DDAVP administration in a healthy adult. AB - We report the development of significant hyponatremia (121 mEq/L) following three daily intravenous doses of desmopressin acetate (DDAVP; 18 micrograms; 0.3 micrograms/kg) in a healthy adult with moderate von Willebrand's disease. Previous reports suggest that clinically important hyponatremia due to DDAVP administration only occurs in the very young, those receiving hypotonic intravenous fluids or those given multiple frequent (e.g., every 8-12 hours) doses of DDAVP. None of these conditions was present in this case. Consideration should be given to monitoring serum sodium levels and fluid balance in patients receiving more than a single dose of DDAVP, even in the absence of previously reported risk factors for the development of hyponatremia. PMID- 8342560 TI - Hb Saint Nazaire (beta 103[G5]Phe-->Ile): a new example of polycythemia due to a hemoglobin variant with increased oxygen affinity. AB - Hb Saint Nazaire [beta 103 (G5) Phe-->Ile] was found in four apparently unrelated French families. The five patients carrying this hemoglobin have been detected because of a moderate erythrocytosis. The structural abnormality of Hb Saint Nazaire concerns the same residue as in Hb Heathrow [beta 103 (G5) Phe-->Leu). A comparative functional study between these two variants showed that the increase in oxygen affinity is much lower in Hb Saint Nazaire than in Hb Heathrow. The replacement of phenylalanine G5, which is localized within the heme pocket, by a leucine abolishes several contacts between the heme and the globin and leads to an environment of the heme having some similarities with that observed in myoglobin. In contrast, the replacement of G5 by an isoleucine is likely to introduce less structural modifications. PMID- 8342561 TI - Detection of the (--SEA) double alpha-globin gene deletion by a simple immunologic assay for embryonic zeta-globin chains. AB - Homozygous alpha-thalassemia [alpha-thal-1], with loss of all four alpha-globin genes, causes lethal hydrops fetalis. The most common mutation producing this syndrome is the Southeast Asian (--SEA) double alpha-globin gene deletion. Erythrocytes from adults heterozygous for the (--SEA) deletion have minute amounts of embryonic zeta-globin chains detectable by anti-zeta-globin monoclonal antibodies. Among 225 peripheral blood samples tested by a simple anti-zeta immunobinding tetrazolium dye test, 81 were positive and 144 were negative. The majority of subjects were of Filipino, Chinese, or Laotian ancestry. All 81 positive samples were confirmed by Bam HI digests and a zeta-cDNA probe to have the (--SEA) mutation. The (--SEA) double alpha-deletion was the only abnormality in 58. In the others, it was combined with alpha-globin or beta-globin mutations, or coincidental iron deficiency. Four other samples from (--SEA) heterozygotes were negative by this immunologic assay. Anti-zeta negative samples included 78 deletions of the total alpha-globin region, (--Tot), 23 single alpha-globin deletions, and a variety of beta-globin mutations; 16 normocytic samples with normal alpha-genes were also negative. Ten anti-zeta positive and 25 anti-zeta negative samples had benign triplicated zeta-globin genes. In this population, the sensitivity of this test was 95%; and specificity for the (--SEA) mutation was 100%. Anti-zeta immunobinding testing provides rapid, simple, and reliable screening for the (--SEA) double alpha-globin deletion, although it does not detect the (--Tot) total alpha-deletions. PMID- 8342562 TI - Consequences of chronic hepatitis C: a review article for the hematologist. AB - The hepatitis C virus (HCV) has been cloned, and assays capable of detecting antibody to HCV recombinant proteins (anti-HCV) have been developed. Concurrent with the cloning and development of the anti-HCV screening tests, trials with interferon alfa-2b have documented biochemical and histologic improvement in the indices of hepatitis C and non-A, non-B (NANB) in patients who were chronically infected. Subsequently, the anti-HCV assays and interferon alfa-2b have become clinically available. These new detection and treatment modalities can now be used in the management of hemophilics and other chronically transfused patients who bear great risk for blood-borne infections and manifest signs of chronic hepatitis. PMID- 8342563 TI - 10(6) Depletion of WBC with CF-2, a new leukocyte removal filter. AB - A new leukocyte removal filter, Nipro CF-2, was evaluated. A non-woven polyester filter, gravity flow device that does not require priming and rinsing after use was developed to remove white blood cells from 400 ml of whole blood or concentrates of 400 ml of whole blood. A flow cytometric technique was developed to measure extremely low WBC counts. To evaluate the efficiency of this filter, leukocyte counts were measured by flow cytometry using a Coulter EPIC-C cytometer. After filtration through a CF-2 filter, more than 99.9999% of WBCs were depleted from 6 of 17 samples. The mean value of WBC depletion was 99.9994%. The CF-2 filter achieved nearly a million-fold depletion of WBCs from whole blood concentrates. PMID- 8342564 TI - Adoptive chemoimmunotherapy using ex vivo activated memory T-cells and cyclophosphamide: tumor lysis syndrome of a metastatic soft tissue sarcoma. AB - Adoptively transferred immune cells in combination with chemotherapeutic agents form the basis for adoptive chemoimmunotherapy (ACIT) of neoplastic disease. Autolymphocytes (ALT-cells) are ex vivo activated peripheral blood lymphocytes (PBL) from tumor-bearing hosts (TBH) that consist primarily of tumor-specific CD45RO+ (memory) T-cells. These ALT-cells combined with cimetidine (CIM) as autolymphocyte therapy (ALT), have previously been demonstrated to be a safe and active form of outpatient adoptive immunotherapy (AIT) in human TBH with metastatic renal cell cancer (RCC). We have previously described an effective ACIT protocol using ALT and cyclophosphamide (CY) for patients with relapsed and refractory non-RCC solid tumors. We now report a case of a patient with a metastatic gastric leiomyosarcoma to the liver, who developed a clinical picture consistent with a tumor-lysis syndrome (TLS), following salvage therapy for his tumor with ACIT using ALT and CY. TLS is a well-known complication resulting from the treatment of rapidly proliferating hematopoietic tumors such as Burkitt's lymphoma and acute lymphocytic leukemia. TLS has also been rarely described in chronic lymphocytic leukemia, as well as certain solid tumors such as breast cancer, small cell lung cancer, and medulloblastoma. However, there have been no previous reports of TLS occurring either secondary to immunotherapy or in sarcomas. The nature of these unusual findings is discussed. PMID- 8342565 TI - Presence of serum antibodies to coagulation protein C in patients with systemic lupus erythematosus is not associated with antigenic or functional protein C deficiencies. AB - Antibodies directed to immunopurified coagulation protein C (PC) were investigated in serum samples from 108 patients with systemic lupus erythematosus (SLE) and found in 12 of them. However, their presence was not associated with antigenic or functional deficiencies of PC, which were documented in 6 and 17 patients, respectively. PMID- 8342566 TI - Phosphatidylserine in the outer leaflet of red blood cells from beta-thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes. AB - Investigation of red blood cells from beta-thalassemia patients by means of prothrombinase assay reveals phosphatidylserine in the outer leaflet of the plasma membrane. This might explain their elevated susceptibility to phagocytosis by macrophages and the chronic hypercoagulable state, frequent thrombotic events, and life-long platelet activation that are found in thalassemic patients. PMID- 8342567 TI - Hemolytic uremic syndrome developing during remission of acute myelomonocytic leukemia. AB - A 47-year-old woman was diagnosed with acute myelomonocytic leukemia (AMMoL) and was treated with combination chemotherapy. After one cycle of remission induction therapy, she entered into complete remission and then received three cycles of consolidation therapy. A month after the last consolidation therapy, she was diagnosed with having the complication of chemotherapy-related HUS (C-HUS). The C HUS improved after initiation of plasma exchange and antiplatelet therapy. In the present case, it seems that the antileukemic agents might play an important role in the development of C-HUS. PMID- 8342568 TI - Amegakaryocytic thrombocytopenia with a positive direct Coombs' test. AB - A 50-year-old previously well woman developed a sudden onset of ecchymoses and petechiae over the trunk and extremities and gum bleeding. There was no history of alcohol use or drug ingestion. Physical examination was normal except for the ecchymoses, purpuric rash, and gum bleeding. Complete blood count showed Hb 8.0 g/dl, leucocytes 10.9 x 10(9)/L with a normal differential, platelets 8 x 10(9)/L and reticulocytes, 4%. The bone marrow was normocellular and showed absence of megakaryocytes; there was normoblastic erythroid hyperplasia and the myelopoiesis was normal. The direct Coombs test result was positive. There was poor response to treatment with prednisone and bolus doses of vincristine. Therapy with danazol resulted in the complete normalization of the blood counts, and the patient remains well 32 months after diagnosis and is currently taking 100 mg danazol daily. PMID- 8342569 TI - Dapsone for autoimmune thrombocytopenic purpura. AB - Twenty-one human immunodeficiency virus (HIV)-free and six HIV-infected adults with autoimmune thrombocytopenic purpura (AITP) were treated with dapsone (100 mg/day). A response was observed in 13 patients (median platelet count before 25 x 10(9)/L, range 3-49; after 109 x 10(9)/L, range 69-241). Thrombocytopenia recurred in four of the responders in whom dapsone was discontinued. No response was observed in 12 patients. Dapsone had to be withdrawn after two weeks of treatment in the remaining two patients and after six to eight weeks in three other patients due to intolerance. No serious hematological complications were observed. These results confirm that dapsone is a safe, inexpensive, and effective treatment of AITP. PMID- 8342570 TI - Translocation (14;15) (q32;q13) in B cell chronic lymphocytic leukemia. PMID- 8342572 TI - Pleural blast crisis in chronic myelogenous leukemia. PMID- 8342571 TI - Successful arthroscopic synovectomy using holmium: Yag laser and FEIBA in a high responder hemophiliac. PMID- 8342573 TI - Familial lupoid thrombocytopenia. AB - Familial lupoid thrombocytopenia affecting three subjects in three generations is reported. All subjects had antinuclear antibodies with or without antibodies to single-stranded DNA, an increase in platelet-associated IgG, and a family member with an autoimmune disease. These findings implicate a genetic contribution. All subjects shared a common HLA haplotype. PMID- 8342574 TI - Recombinant granulocyte-macrophage colony-stimulating factor modulates in vitro function of the peripheral blood mononuclear cells in lipoid nephrosis. AB - The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the in vitro proliferation of peripheral blood lymphocytes (PBL) was evaluated in patients with lipoid nephrosis (LN). The cytokine increased the proliferation of LN PBL in response to phytohemagglutinin (PHA), measured by the [3H]thymidine uptake. The effects were abrogated by antibody against human GM CSF. We then investigated the effect of GM-CSF on the release of interleukin-1 (IL-1) from peripheral blood monocytes (PBM) in LN patients and normals. In vitro IL-1 production by LN PBM treated with lipopolysaccharide (LPS) was enhanced by coculture with GM-CSF. Potentiation was approximately 2-fold. The immunological identity of the thymocyte comitogenic activity as IL-1 was confirmed by neutralization with a specific rabbit antihuman IL-1 antiserum. Taken together, these observations suggest that one mechanism by which GM-CSF acts to restore immune responses in LN patients may be enhancing the signals which enable activated monocytes/macrophages to secrete IL-1. PMID- 8342575 TI - Urinary acidification response to furosemide administration in patients on low dose cyclosporine therapy. AB - The response of urinary acidification parameters and electrolytes to furosemide administration was prospectively studied in 9 psoriatic patients treated with a low-dose cyclosporine A schedule (initial dose: 5 mg/kg body weight) before beginning cyclosporine A, after 3 months on cyclosporine A and 1 month after cyclosporine A withdrawal. The test was also performed in 29 psoriatic patients after 3 months on 5 mg/kg body weight cyclosporine A treatment. There were no significant differences between before and after cyclosporine A treatment regarding furosemide-induced changes in urinary volume, sodium or potassium excretion. Contrarily, the post-furosemide urinary pH decrease and ammonium and titrable acid increase were significantly lower in cyclosporine-A-treated patients. Five of the 29 studied patients showed abnormal furosemide tests (17%). These patients had lower total serum CO2, urea and creatinine but similar serum potassium and fractional potassium excretion. We conclude that some patients treated with low-dose cyclosporine A therapy develop an abnormal tubular distal response to furosemide administration, suggesting an alteration in the H(+) ATPase pump or a voltage-dependent mechanism. PMID- 8342576 TI - Bone mineral density in patients with end-stage renal failure. AB - Renal osteodystrophy is a well-recognized complication of chronic renal failure (CRF) and is associated with a marked morbidity. Bone mineral density (BMD) has been shown to be the best predictor of fracture risk in different circumstances. In this cross-sectional study, we measured BMD using dual photon absorptiometry at three skeletal sites of functional importance such as the lumbar spine (LS), the femoral shaft (FS) and the femoral neck (FN) in 106 patients with end-stage renal failure (11 predialysis patients and 95 patients on maintenance dialysis). These skeletal sites are characterized by various relative amounts of trabecular and cortical bone. The results indicate that decreased bone mass was detectable in all skeletal sites before the beginning of dialysis and that BMD was negatively related to dialysis duration in LS and FS. Nevertheless, the deleterious effects of renal osteodystrophy were more pronounced at the FS level, where cortical bone is predominant. A separate analysis of BMD in both sexes revealed that females presented a more important bone loss in both cortical and trabecular bone than males. We did not find any significant difference in BMD at the three measured sites between patients on continuous ambulatory peritoneal dialysis and on regular hemodialysis. This study emphasizes the need to pay more attention to the prevention of bone loss in patients on CRF before the start of dialysis therapy, and to the fact that the female population might display a more pronounced susceptibility to bone loss. PMID- 8342577 TI - Acute nephropathy of organotin compounds. AB - Three patients who developed acute nephropathy following ingestion of triphenyltin acetate (TPTA) are described. All of them had significant proteinuria, azotemia, and polyuria. Mild neurological manifestations in all patients were also noted. Hematuria and pyuria were noted in 1 severely poisoned patient. Evidence for hepatitis was present in 2 patients, and for pancreatitis in 1. Renal biopsy showed focal fusion of glomerular cell processes and proximal tubular damage with cellular necrosis. Two patients survived with complete recovery of renal functions. One old patient died of aspiration pneumonia. Acute nephropathy following organotin intoxication appears to result mainly from proximal renal tubular damage with a benign and reversible clinical course. PMID- 8342578 TI - Renal concentrating capacity test by desmopressin in children: intranasal or intravenous route? AB - Intranasal administration of desmopressin (dDAVP) is frequently used to test renal concentrating capacity in children. However, the bioavailability of intranasal dDAVP is about 10% and may be modified by nasal congestion. The study aimed to compare the efficacy of intranasal dDAVP with an equivalent dose of intravenous dDAVP for a renal concentrating capacity test in children. We studied 18 children aged 12.6 +/- 3.8 years weighing more than 20 kg in whom a dDAVP test was indicated as part of global renal function evaluation. Spray applicator (Minirin Spray) was used for intranasal administration (20-40 micrograms according to BW); the dose of intravenous dDAVP (Minirin IV) was reduced to 10% (2-4 micrograms according to BW). A randomized sequence was used for the first intranasal or intravenous dDAVP test; the second alternate test was repeated in the same children in a time interval ranging from 1 to 3 weeks. Osmolality of the urine (Uosm, mosm/kg) was determined before (T0), then 2 (T2) and 4 (T4) h after dDAVP administration. There was no significant difference in Uosm at T0 (intranasal = 480 +/- 212, intravenous = 443 +/- 168 mosm/kg), T2 (604 +/- 226 and 542 +/- 173 mosm/kg, respectively), and T4 (657 +/- 206 and 629 +/- 190 mosm/kg, respectively). There was an obvious correlation between intranasal and intravenous Uosm at T4 (r2 = 0.826; p = 0.001). Even if intravenous dDAVP is of theoretical interest, intranasal administration of dDAVP using a spray applicator can be considered as first-choice method for a renal concentrating capacity test in children weighing more than 20 kg. PMID- 8342579 TI - Difference between renal failure associated with methylprednisolone pulse therapy and deterioration of renal function unrelated to methylprednisolone therapy. AB - In this study, we attempted to analyze the differences between renal failure associated with methylprednisolone (MP) pulse therapy and natural deterioration of renal function that was unrelated to MP administration. Of 80 patients with renal or collagen disease who received MP pulse therapy at our hospitals, 13 were selected for the study whose serum creatinine levels increased more than 0.5 mg/dl from baseline values following therapy. Somewhat arbitrarily, 7 patients were placed in an MP-associated renal deterioration group (group 1) in which serum creatinine levels returned naturally, or following induced diuresis, to baseline levels, and 6 patients in an MP-independent natural deterioration group (group 2) in which renal function progressively deteriorated. Renal function similarly deteriorated in the two groups following pulse therapy, irrespective of the degree of crescent formation. Our data suggested that hypoproteinemia is the most important index for differentiating MP-associated renal failure from natural deterioration of renal function unrelated to MP pulse therapy. In patients that are nephrotic and have impaired renal function, worsening of renal function following pulse therapy may partly be due to transient MP-associated renal failure. On the other hand, in patients without hypoproteinemia, worsening of renal function is most likely due to active primary disease and is probably not associated with MP pulse therapy. PMID- 8342580 TI - Mineralocorticoid therapy lowers serum potassium in patients with end-stage renal disease. AB - Hyperkalemia is a commonly encountered problem in dialysis patients with end stage renal disease. In this study we evaluated the effect of mineralocorticoid therapy (MCT; fludrocortisone 0.1-0.3 mg per os daily) on serum potassium of hyperkalemic end-stage renal disease patients. Consecutive monthly clinical and biochemical profiles 3-6 months before and after MCT were compared. Twenty-one patients with a mean age (+/- SE) of 54 +/- 4 years (11 male and 10 female) were studied. Two patients were dropped from this study because they required a change in prescription of dialysis after starting MCT. Mean serum potassium levels significantly fell (p < 0.001) during the post-MCT period (4.9 +/- 0.1 mEq/l) compared with potassium levels during the pre-MCT (5.6 +/- 0.1 mEq/l) period. All patients except 1 showed a reduction in serum potassium levels after MCT. Pre- and post-MCT values were not different for body weight, mean blood pressure, blood urea nitrogen, serum glutamic-oxaloacetic transaminase, lactate dehydrogenase, sodium, chloride, bicarbonate, creatinine and albumin. Since the majority of the patients were anuric (n = 15), a decrease in serum potassium values in the post-MCT period was not due to loss of potassium in the urine. MCT appears to decrease serum potassium values in patients with end-stage renal disease by extrarenal mechanisms. We conclude that MCT can be used safely to lower serum potassium in patients with end-stage renal disease. PMID- 8342581 TI - Influence of thalassemia on the response to recombinant human erythropoietin in dialysis patients. AB - Thalassemia is a common genetic disorder among the South Chinese. To see if thalassemia would adversely affect the erythrocyte response to recombinant human erythropoietin (rHuEPO, Epogen) in dialysis patients, the response to rHuEPO in 4 dialysis patients with thalassemic traits (thal-t) was compared with that of 4 control patients who were matched for age, sex, mode of dialysis and baseline hemoglobin levels over a 6-month period. Patients with thal-t showed a reduced erythrocyte response to rHuEPO compared to control dialysis patients as reflected by a reduced reticulocyte index, a slower rise in hemoglobin or hematocrit levels, requirement of a higher cumulated dose of rHuEPO to achieve a target hemoglobin of 10 g/dl and a higher maintenance dose of rHuEPO. A dialysis patient with hemoglobin H disease (HbHD) was also studied. He failed to respond to rHuEPO despite that the dose was increased to 250 U/kg/week. In contrast, his matched control dialysis patient, despite a lower baseline hemoglobin level (6.1 versus 8.8 g/dl), was able to reach a target hemoglobin level of 10 g/dl by 6 weeks and could be maintained at this level with 50 U/kg/week. The patient with HbHD had splenomegaly and a higher baseline serum erythropoietin level, reticulocyte count, serum bilirubin, serum ferritin and serum iron saturation than control patients and patients with thal-t. It was concluded that thal-t reduces the erythrocyte response to rHuEPO in dialysis patients and that in the presence of active hemolysis and enhanced endogenous erythropoietin secretion, dialysis patients with HbHD are resistant to treatment with rHuEPO. PMID- 8342582 TI - Treatment of severe secondary hyperparathyroidism with administration of calcium carbonate, intermittent high oral doses of 1,25-dihydroxyvitamin D3 and dialysate with 3 mEq/1 calcium concentration. AB - In this study, we evaluated the effect of long-term administration of daily calcium carbonate (2-4 g/day) and intermittent high oral doses of 1,25 dihydroxyvitamin D3 [1,25-(OH)2D3, 3-4 micrograms, given twice a week] in conjunction with a 3-mEq/1 calcium concentration in the dialysate for the treatment of severe secondary hyperparathyroidism in 6 hemodialysis patients. All patients had reduced serum levels of 1,25-(OH)2D3, which increased significantly (p < 0.005) reaching the maximum level in the 4th month. Serum total and ionized calcium levels significantly increased also, in relation to those before treatment. No patients developed hypercalcemia. Serum phosphorus did not significantly change during the study. Initial serum intact parathyroid hormone (PTH) (1,241 +/- 233 pg/ml, mean +/- SEM) markedly decreased after starting treatment with 1,25-(OH)2D3, being 542 +/- 174 pg/ml in the 5th month and 477 +/- 174 pg/ml in the 8th month. These changes are statistically significant (p < 0.05 and < 0.007, respectively). Alkaline phosphatase behavior was similar to that of intact PTH. A constant direct correlation between intact PTH and alkaline phosphatase and an inverse significant correlation between intact PTH and 1,25 (OH)2D3 was evidenced by us. We conclude that oral 1,25-(OH)2D3 pulse therapy is very effective in suppressing PTH secretion. The administration of calcium carbonate and the use of dialysate with a reduced calcium concentration would allow to prevent hyperphosphatemia and the administration of high oral doses of 1,25-(OH)2D3 without concomitant hypercalcemia. PMID- 8342583 TI - Elevated basal levels of cytosolic calcium of thymocytes in chronic renal failure. AB - The basal levels of cytosolic calcium ([Ca2+]i) in rats and/or humans with chronic renal failure (CRF) are elevated in many cells including brain synaptosomes, pancreatic islets, polymorphonuclear leukocytes, platelets and B and T cells. This rise in [Ca2+]i has been attributed to the state of secondary hyperparathyroidism of CRF. These observations have led to the proposition that CRF is a state of cellular calcium intoxication mediated by excess parathyroid hormone (PTH). The documentation of a high basal level of [Ca2+]i in other cells is needed to provide further support for this postulate. The present study evaluated the basal levels of [Ca2+]i of thymocyte, which are targets for PTH action, in normal, CRF, and CRF parathyroidectomized (CRF-PTX) rats. We also examined whether CRF affects the phenotype expression (Thy-1, CD4 and CD8) in thymocytes. The results showed that the basal levels of [Ca2+]i in thymocytes from CRF rats (81 +/- 3.7 nM) are significantly (p < 0.01) higher than those in normal animals (60 +/- 2.9 nM). PTX of CRF animals prevented the elevation in the basal levels of [Ca2+]i of thymocytes; in these animals, the levels were 59 +/- 2.8 nM. Neither CRF nor the elevation in [Ca2+]i of thymocytes affected their phenotype expression. PMID- 8342584 TI - A case of Guillain-Barre syndrome with focal segmental glomerulosclerosis. AB - Acute inflammatory polyneuropathy or Guillain-Barre syndrome may be associated with glomerulonephritis, especially membranous nephropathy. This paper details the case of a 73-year-old woman presenting with acute onset of Guillain-Barre syndrome associated with an abnormal urinary sediment and significant proteinuria. Renal biopsy was consistent with focal segmental glomerulosclerosis. Despite an initial response to plasmapheresis, the patient's polyneuropathy deteriorated and subsequently improved with corticosteroid therapy. Simultaneously, her proteinuria and urinary sediment also improved. This implies that this was not a chance association. A brief discussion of the association between Guillain-Barre syndrome and glomerulopathies is undertaken. PMID- 8342585 TI - Steroid-responsive renal insufficiency due to idiopathic granulomatous tubulointerstitial nephritis. AB - A 26-year-old male was admitted to our hospital having suffered from subfever, sterile pyuria and renal insufficiency for 1 year. There had been no apparent hematuria/proteinuria, and evidence of infection, allergy or intoxication was not demonstrated. Open renal biopsy revealed severe tubulointerstitial changes with granuloma accompanied by neither caseous necrosis nor giant cells. Infiltrating cells mostly consisted of CD4 and CD8 T cells, and some proximal tubular cells presented MHC class II antigen. Following the negative culture of biopsied specimen for acid-fast bacilli, diagnosis of idiopathic granulomatous tubulointerstitial nephritis was made, and steroid therapy was started. Two months later, pyuria disappeared and renal function improved significantly, proving the effectiveness of steroid on idiopathic granulomatous tubulointerstitial nephritis. PMID- 8342586 TI - Transplantation of kidneys from a donor with Neisseria meningitidis infection. PMID- 8342587 TI - Immunocytochemical localization of ProANF 1-30, ProANF 31-67, atrial natriuretic factor and urodilatin in the human kidney. AB - Whether ProANF 1-30 [first 30 amino acids (a.a.) of the 126-a.a. atrial natriuretic factor (ANF) prohormone] and ProANF 31-67 (a.a. 31-67 of this prohormone) with their natriuretic and diuretic properties are present within the human kidney is unknown. In the present investigation, ProANFs 1-30 and 31-67 as well as ANF (a.a. 99-126) of the ANF prohormone localized to the subbrush border of the pars convoluta and pars recta of the proximal tubules of the human kidney with immunoperoxidase staining. Immunofluorescent studies revealed that each of these peptides had a strong inclination for the perinuclear region in the proximal and distal tubules. ProANFs 1-30, 31-67 and 99-126 (i.e. ANF) also localized with both immunoperoxidase and immunofluorescent staining to the coritcal collecting ducts, glomeruli, and peritubular and interstitial blood vessels. ANF immunoperoxidase staining was particularly striking in the endothelium of interstitial arteries and vasa recta. In the glomeruli, prominent staining was noted in the peripheral glomerular capillary wall and in some of the visceral epithelial cells. In contrast, urodilatin (i.e. a.a. 95-126 of the ANF prohormone) was not found in the proximal tubules, but weak staining was found in the distal tubules and interstitial vessels with some but not all glomeruli, peritubular vessels, cortical collecting tubules and outer medullary nephrons weakly staining by immunoperoxidase and immunofluorescent methods. The whole prohormone being present in the kidney was suggested by immunological recognition of both the N- and C-termini of the ANF prohormone by radioimmunoassays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342588 TI - Acute effects of furosemide on blood pressure in functionally anephric, volume expanded rats. AB - The hypotensive effect of loop diuretics is primarily mediated by a decrease in extracellular fluid volume that follows the intense diuresis. In the present study we investigated whether furosemide (1.25 mg/kg i.v.) can acutely lower blood pressure independently of its diuretic action. The experiments were performed in four groups of male Wistar rats: (a) rats in which furosemide was administered after bilateral ligation of renal vessels and saline (0.9% NaCl at a rate of 0.25 ml/min to a final volume of 1% of body weight) infusion; (b) rats in which furosemide was injected after bilateral ligation of ureters and saline infusion; (c) rats pretreated with indomethacin (3 mg/kg i.p. for 4 days) in which furosemide was injected after bilateral ligation of ureters and saline infusion; (d) sham-operated rats with intact kidneys. All the groups were compared with appropriate time controls. After furosemide injection, heart rate and blood pressure were serially recorded for 30 min by plethysmography. Hematocrit, plasma 6-keto-prostaglandin F1 alpha levels and plasma renin activity were measured at baseline and 20 min after furosemide injection. No change in blood pressure followed furosemide administration in rats with ligation of the renal vessels. Conversely, furosemide induced a rapid and significant fall in blood pressure associated with a significant increase in heart rate in rats with ligation of the ureters and rats with intact kidneys. Indomethacin pretreatment prevented the furosemide-induced decrease in blood pressure in rats with ligation of the ureters. Hematocrit and plasma 6-keto-prostaglandin F1 alpha levels were not affected by furosemide in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342589 TI - Keratinocytes: key immunocytes of the integument. PMID- 8342590 TI - The placenta revealed. PMID- 8342591 TI - Interleukin-4 down-regulates adult human astrocyte DNA synthesis and proliferation. AB - The T lymphocyte-derived cytokine, interleukin-4 (IL-4), was found to inhibit dose dependently basal DNA synthesis of cultured non-neoplastic human astrocytes isolated from epilepsy white matter tissue. The mitogenic effect of tumor necrosis factor on astrocytes was also inhibited by IL-4, and the inhibitory effect was abrogated by anti-IL-4 antibody but not by irrelevant IgG. Immunofluorescent analysis indicated significantly reduced numbers of glial fibrillary acidic protein-positive astrocytes incorporating nuclear bromodeoxyuridine in IL-4-treated cultures compared to control. These findings indicate that human adult astrocyte proliferation, in contrast to that reported for endothelial cells or fibroblasts, is sensitive to down-regulation by IL-4. PMID- 8342592 TI - Cytotoxic potential of intraepithelial lymphocytes (IELs). Presence of TIA-1, the cytolytic granule-associated protein, in human IELs in normal and diseased intestine. AB - Human intestinal intraepithelial lymphocytes (IELs) have phenotypic characteristics of cytotoxic T cells, yet a cytotoxic function has not been demonstrated in redirected lysis assays. A monoclonal antibody that reacts with a cytotoxic granule-associated protein, TIA-1, was used in this study to identify this protein in many, but not all, IELs of normal human proximal small intestine. Furthermore, in active celiac disease, in which the number of IELs is significantly increased, a corresponding increase in the number of TIA-1 cells was found. These results indicate that whereas cytotoxicity of human IELs has been difficult to demonstrate, they contain at least one of the proteins associated with cytotoxicity, and a failure to demonstrate this function may be related to the in vitro assay system used. PMID- 8342593 TI - Spatial and temporal patterns of immunoreactive transforming growth factor beta 1, beta 2, and beta 3 during excisional wound repair. AB - Transforming growth factor beta (TGF-beta) regulates cellular growth and differentiation and stimulates the synthesis and secretion of protein constituents of the extracellular matrix. Three isoforms of TGF-beta have been found in mammals. Although the biological activities of TGF-beta 1, TGF-beta 2, and TGF-beta 3 are similar at the level of cell culture, distinct in vivo functions for these molecules are emerging. To gain insight into the role of each isoform in wound repair, antibodies specific for each isoform of TGF-beta were used to examine excisional wound repair. Marked differences in the temporal and spatial relationships for immunoreactive TGF-beta 1, -beta 2, and -beta 3 were noted throughout the repair process. TGF-beta 2 and TGF-beta 3 were prevalent by 24 hours after excisional wounding, and strong immunoreactivity was observed in the migrating epidermis. Subtle changes in immunoreactivity occurred for TGF-beta 2 and TGF-beta 3 in cells of the epidermal appendages, mesenchymal derivatives, granulation tissue, and the underlying dermis throughout wound repair. In contrast, TGF-beta 1 was not associated with any undifferentiated cells and was not present in the dermis and most dermal structures in both nonwounded skin or wounds until day 5 after wounding, when re-epithelialization was complete. Following re-epithelialization, TGF-beta 2 and TGF-beta 3 were present in all four layers of stratum corneum of the differentiating epidermis. All three TGF beta isoforms were present in mesenchymal cells and basal lamina, suggesting their role in the modulation of dermal-epidermal interaction during wound repair. Our observations support individual in vivo function for TGF-beta isoforms in cutaneous wound repair. PMID- 8342594 TI - Effects of late reperfusion on infarct expansion and infarct healing in conscious rats. AB - We examined the effects of late reperfusion on infarct expansion and infarct healing process in conscious rats. Coronary occlusion and reperfusion were carried out in conscious rats 1 week after appropriate surgical preparations. The rats were randomized into the following four groups: sham operated, permanent occlusion, early reperfusion (i.e., reperfusion performed 1 hour after occlusion), and late reperfusion (i.e., reperfusion performed 6 hours after occlusion). Histological examination was performed 7 days after coronary occlusion. In the early reperfusion group, infarct size and expansion were reduced when compared to the permanent occlusion group. In rats subjected to late reperfusion, infarct size and expansion were not different from those in the permanent occlusion group. The extent of unresorbed necrotic myocardium in areas of infarcted scar was reduced in both early and late reperfusion groups. Infiltration by neutrophilic cells into areas of necrotic myocardium 16 hours after myocardial infarction was increased in both reperfusion groups. Infiltration by macrophages 3 days after infarction was also increased in both reperfusion groups. Late reperfusion, therefore, does not affect infarct expansion, but does contribute to the acceleration of the infarct healing process. PMID- 8342595 TI - Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. AB - In experimental autoimmune encephalomyelitis (EAE) myelin-specific T lymphocytes attack the myelinated tissue of the central nervous system (CNS). In the Lewis rat, EAE as a rule has an acute, monophasic course. With spontaneous clinical recovery the inflammatory CNS infiltrates are cleared from the nervous tissue within a few days. This is well in line with the remarkably low incidence of myelin-specific T cells present in EAE infiltrate. Combining immunocytochemical techniques, ultrastructural criteria and in situ nick translation we found up to 49% of T lymphocytes in EAE lesions showing signs of apoptosis at the time of recovery from disease. Our results suggest that apoptosis of T lymphocytes may be one possible mechanism to eliminate T lymphocytes from inflammatory brain lesions. PMID- 8342596 TI - Villitis of unknown etiology is associated with major infiltration of fetal tissue by maternal inflammatory cells. AB - Villitis of unknown etiology (VUE) is a common placental lesion and an important cause of intrauterine growth retardation and recurrent reproductive failure. Two theories have been proposed to explain VUE. One proposes that VUE is an exclusively fetal immune response to microbial antigen, whereas the other suggests that maternal cells cross the maternal-fetal interface and mount an immune response to fetal antigens. To differentiate between these alternatives, we performed in situ hybridization using X and Y chromosome-specific probes and immunostaining for CD3 and CD45 on VUE placentas from male infants. A total of eight foci and 40 villi were studied from four male VUE placentas. Controls included nonaffected villi from each male VUE placenta, a female VUE placenta, and male and female tonsils. Affected villi showed a major proportion of XX (maternal) cells (range 30 to 54%). An appropriate percentage of the remaining (fetal) cells contained Y chromosomes. The fraction of cells within the eight foci staining for CD3 (T lymphocytes) ranged from 34 to 57%, whereas the fraction staining for CD45/LCA (total leukocytes) ranged from 45 to 74%. The proportion of maternal cells within each focus was significantly correlated with the number of CD3-positive T lymphocytes but not with the number of CD3-negative leukocytes. We conclude that maternal cells, probably CD3-positive T cells, cross the maternofetal barrier and participate in VUE. PMID- 8342597 TI - Expression of tumor necrosis factor-alpha and its mRNA in the endometrial mucosa during the menstrual cycle. AB - Endometrial biopsies, collected at various phases of the menstrual cycle, were examined for the presence of tumor necrosis factor-alpha (TNF-alpha) by histochemistry, and TNF-alpha mRNA by in situ hybridization and Northern blotting. During the proliferative phase, TNF-alpha and TNF-alpha mRNA were not detected or were at low levels. During the secretory phase, the TNF-alpha mRNA level was increased and observed in the wall of coiled arteries. TNF-alpha was detected both in the wall of the coiled arteries and, in highest concentration, within the epithelial cells. In regard to the capacity of TNF-alpha to induce a hemorrhagic necrosis in various tissues, this study suggests that an overproduction of TNF-alpha within the small arteries of the endometrial mucosa might be responsible for menstruation. PMID- 8342598 TI - Plasma protein insudation as an index of early coronary atherogenesis. AB - Two hundred ninety-nine paraffin-embedded coronary artery blocks from 68 autopsy cases were serially sectioned. The blocks were selected to provide a range from normal through various stages of atherosclerosis, and sections were examined with the indirect immunofluorescence technique for intramural distribution of plasma albumin, fibrinogen, and immunoglobulin gamma (IgG). Cryostat-sections of 44 blocks from 22 of the same cases were examined with the same technique for distribution of apolipoprotein B. Alteration of protein insudation in the artery wall was a sensitive index of coronary atherogenesis. The sequence in which these proteins were involved in the initiation and development of early atherosclerotic lesions was analyzed by determining the average relative intimal thickness and relative lumen size that was associated with the first occurrence of altered insudation of each of these proteins. Results indicate that changed plasma albumin insudation is the earliest sign of a focal intimal lesion, and increasing albumin insudation shows the strongest association with intimal plaque growth. The other proteins tested showed altered insudation, in the order IgG, fibrinogen, apolipoprotein B. The results indicate that a progressive increase in permeability of the coronary artery endothelium occurs in the early stages of atherogenesis. Patterns of IgG localization provide evidence of both early systemic and subsequent local immune reactions being involved in atherogenesis. Altered albumin and apolipoprotein B insudation levels have stronger correlation coefficients with relative intimal thickness and relative lumen size than do those IgG and fibrinogen. The extremely high correlation coefficients shown by albumin emphasizes the importance of edema in determining plaque size and lumen stenosis. PMID- 8342599 TI - Elevated expression of basic fibroblast growth factor in an immortalized rabbit smooth muscle cell line. AB - Intimal smooth muscle cell accumulation is regarded as an important component of atherosclerotic plaque formation, angioplasty-induced restenosis, and vascular graft occlusion. Vascular smooth muscle cells can both express and respond to acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF); therefore, under certain conditions these polypeptides may regulate smooth muscle cell growth in an autocrine manner. Previous studies using smooth muscle cells cultured in vitro have identified factors that can enhance aFGF and bFGF gene expression. In this study, we assayed fibroblast growth factor gene expression in a spontaneously immortalized rabbit smooth muscle cell line. In contrast to "normal" rabbit smooth muscle cells, these immortalized cells acquire an altered morphology and enhanced proliferative rate during; cell passaging in vitro. Both "normal" and immortalized rabbit smooth muscle cells express bFGF but not aFGF transcripts. RNA gel blot hybridization, reverse transcription/polymerase chain reaction amplification, and Western blotting techniques demonstrate that bFGF expression in the immortalized smooth muscle cell line increases as a function of passage level. This continuous cell line should prove valuable for studying both the regulation of bFGF synthesis and the control of vascular smooth muscle cell proliferation. PMID- 8342600 TI - Growth and invasion of human melanomas in human skin grafted to immunodeficient mice. AB - An orthotopic model of human melanoma was developed in which malignant cells were injected into human skin grafted to nude and SCID mice. Melanoma cells proliferated and invaded the human skin grafts with characteristic patterns. Three of six melanomas grew as multiple nodules and infiltered the grafts without major architectural changes in the dermis, whereas the others invaded the dermis along collagen fibers with prominent endothelial vessels. By contrast, melanoma cells inoculated into mouse skin grew as diffusely expanding nodules that did not invade the murine dermis. In human skin grafts, human melanoma cells were angiogenic for human blood vessels, and murine vessels were only found at the periphery of grafts. Tumor cells invaded the human vessels, and four out of seven cell lines metastasized to lungs, suggesting that this model is useful to determine in vivo the interactions between normal and malignant human cells. PMID- 8342601 TI - Cooperation of Ito cells and hepatocytes in the deposition of an extracellular matrix in vitro. AB - Cellular and molecular mechanisms involved in the deposition of extracellular matrix components in both normal and fibrotic liver are still poorly understood. We have investigated the influence of cooperation between Ito cells and hepatocytes in matrix deposition in vitro. Immunoprecipitation of radiolabeled proteins from media of 5-day-old Ito cell primary cultures showed that these cells secreted high levels of the major basement membrane components, ie, collagen IV, laminin, and entactin/nidogen. By immunocytochemistry, precursors of basement membrane components were found intracellularly, but only scarce deposits were seen around the cells. When hepatocytes were added to 2-day-old Ito cell primary cultures, they established close contacts with Ito cells in less than 24 hours and expressed ZO-1, a tight junction-associated protein not detectable in standard hepatocyte culture. Cytochemistry analysis revealed an abundant extracellular matrix deposited over hepatocyte cords and between hepatocytes and Ito cells. Immunocytochemistry studies showed that this matrix contained laminin, fibronectin, and collagens proIII and IV. These data indicate that a high level of matrix protein synthesis by liver cells in vitro is not sufficient to induce extracellular matrix deposition, and that cell-cell interactions are strongly involved in this process. Hepatocyte/Ito cell co-culture, which may reflect the actual situation in vivo, represents a useful tool for studying liver fibrogenesis. PMID- 8342602 TI - K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. AB - We examined 82 surgically resected or biopsied, formalin-fixed, paraffin-embedded primary adenocarcinomas of the pancreas for the presence of activating point mutations in codon 12 of the K-ras oncogene. Mutations were detected using primer mediated, mutant-enriched, polymerase chain reaction-restriction fragment length polymorphism analysis and characterized further by allele-specific oligonucleotide hybridization. This combination of mutant-enriched polymerase chain reaction-restriction fragment length polymorphism analysis and allele specific oligonucleotide hybridization results in a rapid and sensitive characterization of the mutations in codon 12 of K-ras. Sixty-eight (83%) of the 82 carcinomas examined harbored a point mutation. Of the 68 mutations, 33 (49%) were guanine to adenine transitions, 27 (39%) were guanine to thymine transversions, and eight (12%) were guanine to cytosine transversions. Mutations were found in carcinomas of the head (61 of 75, 81%) as well as in carcinomas of the body or tail (seven of seven, 100%) of the pancreas. The overall prevalence of K-ras point mutations in adenocarcinomas of the pancreas obtained from patients who smoked cigarettes at some point during their lives (88%; 86% in current smokers and 89% in ex-smokers) was greater than that seen in pancreatic adenocarcinomas from patients who never smoked cigarettes (68%, P = 0.046). The presence of K-ras point mutations did not correlate with tumor ploidy, tumor proliferating index, or patient survival. These results demonstrate that primer mediated, mutant-enriched polymerase chain reaction-restriction fragment length polymorphism analysis combined with allele-specific oligonucleotide hybridization can be used to detect and characterize mutations in codon 12 of the K-ras oncogene in formalin-fixed, paraffin-embedded tissues, and the results confirm that activating point mutations in codon 12 of the K-ras oncogene occur frequently in adenocarcinomas of the pancreas. PMID- 8342603 TI - Biochemical and anatomical redistribution of tau protein in Alzheimer's disease. AB - We have developed assays that distinguish tau protein incorporated into the core structure of the paired helical filament (PHF) from non-PHF tau protein in brain tissue, whether soluble or insoluble. The PHF content was 19-fold greater in Alzheimer's disease cases compared with cognitively intact controls, and in temporal cortex the difference was 40-fold. There was a threefold decrease in soluble tau protein in Alzheimer's disease cases compared with normal age-matched controls, the decrease being greatest in frontal cortex. The PHF content was closely correlated with the number of tau-immunoreactive dystrophic neurites in plaques and throughout the neuropil, whereas counts of neurofibrillary tangles were poorer predictors of PHF content. beta-Amyloid deposits correlated neither with PHF content nor with neurofibrillary pathology. These findings suggest that Alzheimer's disease is characterized by a substantial redistribution of available tau protein from free to PHF-incorporated fractions and that PHF accumulation may be important in neurites as well as tangles in predicting the extent of cognitive impairment in Alzheimer's disease. PMID- 8342604 TI - Development of functional diversity in mouse macrophages. Mutual exclusion of two phenotypic states. AB - The objective of this study was to investigate the mechanisms that contribute to the generation of macrophage functional diversity. Exposure of mouse bone marrow derived macrophages to beta-1,3-glucan, a particulate inflammatory stimulus, or polyinosinate-polycytidylate (poly[I:C]), a stimulus of macrophage cytocidal activation, induced distinct and stimulus-specific patterns of gene expression. These changes were characterized by an up-regulation of the expression of the acid hydrolase beta-glucuronidase and platelet-derived growth factor B following incubation with beta-1,3-glucan and a stimulation of the expression of the complement component Bf, beta-interferon, and the reactive nitrogen intermediates NO2/NO3 during incubation with poly[I:C]. The induction of Bf expression by poly[I:C] could not be explained on the basis of distinct subpopulations of cells since in situ hybridization with a mouse Bf cRNA probe revealed a uniform and substantial increase in Bf expression by the entire population of cells. Incubation of macrophages with beta-1,3-glucan before stimulation with poly[I:C] was found to strongly attenuate the expression of Bf and beta-interferon. Conversely, incubation with poly[I:C] prior to exposure to beta-1,3-glucan substantially blocked the stimulation of beta-glucuronidase and platelet-derived growth factor B expression, indicating that these two responses were expressed in a mutually antagonistic fashion. However, after removal of either stimulus and following a period in which the primary response was allowed to decay, the cells regained their capacity to subsequently respond to either the same stimulus or to a different stimulus. Collectively, these findings indicate, first, that the heterogeneity of gene expression seen in response to poly[I:C] represents an adaptive response of the entire macrophage population rather than the restricted responses of distinct subpopulations of cells. Second, macrophages respond to these stimuli in a sequential fashion. These findings thus have a significant bearing on our understanding of the regulation of macrophage heterogeneity in host defense. PMID- 8342605 TI - Detection of two forms of GP330. Their role in Heymann nephritis. AB - Heymann nephritis is characterized by glomerular immune deposits that contain a glycoprotein called gp330. The deposits are believed to result from shedding of immune complexes formed on podocytes. Complexes are also shed from proximal tubule cells, when antibodies combine with gp330 on the cell surface. We performed the present study to investigate what portion of the gp330 molecule is shed, using a rabbit antiserum against a peptide deduced to be in the cytoplasmic domain of gp330, as well as a rabbit antiserum and two monoclonal antibodies that recognize extracellular epitopes of gp330. The anti-cytoplasmic peptide antiserum precipitated from Fx1A (a crude renal cortical membrane preparation), a protein with a mass of about 440 kd that was reactive with two monoclonal anti-gp330 antibodies. (In our experiments, the protein called gp330 generally has a mass estimated to be about 440 kd.) The anti-cytoplasmic peptide antiserum also reacted with a truncated gp330 protein produced in transfected COS cells. Immunohistochemical studies showed that all the antibodies recognized the same group of epithelial cells. However, as seen in immunoultrastructural studies of proximal tubules, the anti-cytoplasmic peptide antiserum reacted only with components at the base of microvilli, whereas the anti-gp330 ectodomain antibodies identified material not only at the base, but over the surface of microvilli as well. In rats with Heymann nephritis, glomerular deposits and material shed into tubule lumens reacted with antibodies against extracellular epitopes of gp330, but not with the anti-cytoplasmic peptide antiserum. We propose that there are two forms of gp330 on the cell surface of proximal renal tubules. One form is restricted to coated pit regions at the base of microvilli and has a cytoplasmic domain containing a sequence deduced from a partial complementary DNA encoding gp330. The other form is present over microvilli (and possibly at the base of microvilli as well) and lacks the cytoplasmic domain deduced from the complementary DNA. The complexes that are shed in Heymann nephritis contain either a portion of gp330 cleaved from the full-length molecule or a form of gp330 that lacks the cytoplasmic domain. PMID- 8342607 TI - Immotile cilia syndrome in pigs. A model for human disease. AB - This paper describes the ultrastructural alterations observed in the tracheal epithelium of six sibling swine suffering from porcine immotile cilia syndrome (PICS) compared with those in human immotile cilia syndrome (HICS). As in some human cases, the tracheal epithelium of these pigs was lined by cilia-lacking cells. A variety of dynein defects in other pigs suffering from PICS have been previously observed. The spectrum of defects affords evidence that the PICS is genetically heterogeneous. Available data suggests that there are many similarities between HICS and PICS. Therefore, it is proposed that PICS may prove to be a useful animal model for the human disease. PMID- 8342608 TI - Source of kidney determines blood pressure in young renal transplanted rats. AB - Recipients of a renal graft from adult stroke-prone spontaneously hypertensive rat (SHRSP) but not normotensive Wistar-Kyoto rat (WKY) donors have been shown to develop posttransplantation hypertension. To investigate whether hypertension would also travel with the kidneys from young prehypertensive SHRSP and whether the age-related increase in blood pressure in F1 hybrids (F1H) bred from SHRSP and WKY parents was attenuated by early bilateral nephrectomy and transplantation of a WKY kidney, we transplanted kidneys from 14 male SHRSP and 16 WKY donors aged 35-42 days to young male F1H. Recipients had both native kidneys removed. Fifteen unilaterally nephrectomized nontransplanted F1H served as controls. At the time when kidneys were harvested for transplantation, systolic blood pressures in young SHRSP and WKY donors were not significantly different (114 +/- 5 vs. 113 +/- 3 mmHg). After transplantation, recipients of an SHRSP kidney rapidly developed posttransplantation hypertension with systolic blood pressures above 180 mmHg at 3 mo after transplantation. In contrast, systolic blood pressure in recipients of a WKY kidney rose only slightly with increasing age and remained significantly lower than in non-transplanted controls. Transplanted rats exhibited normal weight gain, and renal function (glomerular filtration rate, renal blood flow) in grafted kidneys was well preserved; plasma renin activity was reduced compared with nontransplanted controls. These data demonstrate that 1) hypertension can be transmitted to normotensive recipients by transplantation of a kidney from young prehypertensive SHRSP donors and 2) the age-related increase in arterial pressure in F1H is attenuated by early bilateral nephrectomy and transplantation of a WKY kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342606 TI - Rabbit models of arthritis: immunolocalization of matrix metalloproteinases and tissue inhibitor of metalloproteinase in synovium and cartilage. AB - The distribution of the matrix metalloproteinases, collagenase, stromelysin, gelatinases A and B, and the tissue inhibitor of metalloproteinases in cartilage and synovium removed from rabbits up to 27 days after induction of two models of arthritis was investigated by immunolocalization. Following intra-articular injection of poly-D-lysine/hyaluronic acid coacervate, collagenase and stromelysin were found bound to cartilage matrix, but there was little increase in chondrocyte synthesis of these enzymes. The synovium underwent a complex wound healing response involving invagination and encapsulation of the coacervate and inflammatory cell debris, during which all four metalloproteinases and tissue inhibitor of metalloproteinase could be immunolocalized. The second model, intra articular injection of ovalbumin into sensitized rabbits, caused considerable chondrocyte necrosis; collagenase was found bound to cartilage matrix on day 13, although again there was little evidence of synthesis by chondrocytes. Inflammatory cell infiltration of meniscoid synovia took place initially, followed by fibrosis involving macrophagelike cells secreting gelatinase A. In both models there was rapid loss of glycosaminoglycan metachromasia from the cartilage matrix. These results are discussed in relation to current knowledge of metalloproteinase involvement in the chronic rheumatoid synovial pannus erosion of cartilage in humans. The data suggest that there are considerable differences between rheumatoid arthritis and these models, and their use must therefore be carefully defined. PMID- 8342609 TI - Regulation of renal glomerular and papillary ANP receptors in rats with experimental heart failure. AB - Rats with aortocaval (A-V) fistula, an experimental model of congestive heart failure (CHF), display high circulating atrial natriuretic peptide (ANP) levels and a markedly blunted natriuretic response to ANP infusion. The present study was designed to evaluate whether alterations in renal ANP receptors may contribute to renal hyporesponsiveness to ANP in experimental CHF. Densities (Bmax) and dissociation constants (Kd) of both the biologically active (ANPA) and clearance receptors (ANPC) were evaluated in glomerular and papillary membranes from A-V fistula rats (n = 18) and sham-operated controls (n = 20). ANPA and ANPC receptor subtypes were assayed by displacement of 125I-ANP-(99-126) bound to glomerular or papillary membranes by increasing concentrations of unlabeled ANP (99-126) or des-(18-22)-ANP-(4-23), an analogue which binds only to ANPC. Seven days after the operation, rats with A-V fistula displayed avid sodium retention, elevated plasma renin activity, and approximately a 10-fold increase in plasma ANP levels. Bmax of total ANP binding sites was significantly decreased in rats with A-V fistula compared with controls (220 +/- 61 vs. 399 +/- 88 fmol/mg protein, P < 0.05). The decrease was mainly due to a reduction in ANPA receptor density (51 +/- 10 vs. 110 +/- 15 fmol/mg protein, P < 0.05) with no change in receptor affinity. Likewise, a significant reduction in the density of ANPA (23 +/- 5 vs. 64 +/- 10 fmol/mg protein, P < 0.05) with no change in receptor affinity was observed in papillary membranes of rats with A-V fistula.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342610 TI - Sodium azide protects against ischemia-induced acute renal failure in rats. AB - Sodium azide (AZ) is a nitrovasodilator with diverse biochemical properties. We found that low doses of AZ led to a profound protective effect against postischemic, acute renal failure (ARF) in rats. AZ, given at 250 micrograms/kg iv, before 25 min of renal artery occlusion (RAO) and again before reperfusion, conferred almost complete protection against loss of kidney function determined 18 h after RAO. The effect of AZ was evidenced by a higher creatinine clearance (+348%) and lower levels of blood urea nitrogen (-69%) and histological renal damage (-50%) compared with ischemic control animals. Indexes of kidney function in AZ-treated animals subjected to RAO were not significantly different from those of nonischemic control animals. Two other nitrovasodilators, sodium nitroprusside and hydralazine, at doses which produced decreases in blood pressure similar to that of AZ, were ineffective at preventing ARF. The beneficial effect of AZ may be due to its known ability to inhibit one or more enzymes including adenosinetriphosphatase, cytochrome-c oxidase, and myeloperoxidase. PMID- 8342611 TI - Polarity of taurine transport in cultured renal epithelial cell lines: LLC-PK1 and MDCK. AB - We characterized taurine transport in two continuous renal epithelial cell lines: LLC-PK1, derived from the proximal tubule of the pig, and the Madin-Darby canine kidney (MDCK), which was originated from the distal tubule of the dog. In the LLC PK1 cell line, taurine transport is greatest at the apical surface of the cell, whereas in the MDCK cell line taurine transport is greatest at the basolateral surface. Both apical and basolateral surfaces of LLC-PK1 and MDCK cells exhibit an adaptive response to the extracellular taurine concentration (medium taurine concentration). Only the basolateral surface of the MDCK cell responded to hyperosmolality with increased taurine accumulation. This indicates differential control of the beta-amino acid transport system by substrate and external tonicity. The function of the beta-amino acid transport system may be different depending on the cell. In the LLC-PK1 cell, there is net transepithelial movement of taurine and changes in transporter activity in response to supply of substrate. In contrast, taurine accumulation by the MDCK cell appears to be a mechanism for adaptation to osmotic stress. PMID- 8342612 TI - Developmentally regulated kallikrein enzymatic activity and gene transcription rate in maturing rat kidneys. AB - Kinins are paracrine vasoactive and growth-modulating peptides. Kidney maturation is accompanied by enhanced accumulation of the mRNA encoding tissue (renal) kallikrein, a serine protease, and a key component of the kallikrein-kinin system. To further delineate the developmental regulation of renal kallikrein, we measured tissue kallikrein activity and gene transcription rate during the latter stages of metanephrogenesis. Active tissue kallikrein was measured in renal homogenates by the amidolytic assay using the fluorogenic substrate D-Val-Leu-Arg 7-amino-4-methylcoumarin (D-VLR-AMC) in the presence or absence of soybean trypsin inhibitor (SBTI). Kallikrein activity was detectable at very low levels in the near-term fetal metanephros. Postnatally, renal kallikrein activity peaked immediately after birth and again at the time of weaning (P < 0.05 vs. other age groups) and remained high in the adult. Mature female rat kidneys contained 30% more active kallikrein than male kidneys (P < 0.05). The SBTI-sensitive D-VLR-AMC hydrolytic activity (due to serine proteases other than tissue kallikrein) accounted for 36-53% of the total renal amidolytic activity. Compared with the 5 day-old newborn, steady-state renal kallikrein mRNA levels increased threefold by day 12 and sixfold by adulthood. Run-on transcription analysis of renal cell nuclei revealed a significant increase in kallikrein gene transcription rate of 80% on day 12 (P < 0.05) and 480% in the adult (P < 0.001). The presence of active kallikrein in the developing kidney and the upregulation of its synthesis at specific time points during postnatal development implicate intrarenal kinins as potential modulators of renal growth and functional maturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342613 TI - V2-like vasopressin receptor mobilizes intracellular Ca2+ in rat medullary collecting tubules. AB - Cytosolic free calcium concentration ([Ca2+]i) was measured in single microdissected rat medullary collecting tubules [outer (OMCD) and inner (IMCD)] to identify receptors involved in vasopressin (AVP)-induced [Ca2+]i increases. In both segments, [Phe2,Orn8]vasotocin ([Phe2,Orn8]VT), a specific V1 agonist, as well as the V2 agonist 1-desamino-8-D-AVP (dDAVP) triggered [Ca2+]i variations. In OMCD, the mean response to 10 nM AVP roughly corresponded to the sum of V1 and V2 agonists effects. In IMCD, dDAVP (10 nM) alone reproduced the calcium response to AVP (delta[Ca2+]i = 243 +/- 34 nM, n = 6, and 248 +/- 27 nM, n = 8, with dDAVP and AVP, respectively). Furthermore, in the same experiments V1 and V2 maximal effects were not additive ([Phe2,Orn8]VT = 154 +/- 21 nM, n = 6; dDAVP + [Phe2,Orn8]VT = 233 +/- 23 nM, n = 9). As AVP, dDAVP released intracellular calcium (delta[Ca2+]i in calcium-free medium = 182 +/- 24 nM, n = 8, vs. 182 +/- 14 nM, n = 6 with 10 nM dDAVP and AVP, respectively). Neither 8-(4-chlorophenyl thio)-adenosine 3',5'-cyclic monophosphate nor forskolin modified [Ca2+]i. A cross-reaction of dDAVP with an oxytocin (OT) receptor can be excluded since 1) the specific OT agonist [Thr4,Gly7]OT (10 nM) increased only slightly [Ca2+]i (delta-[Ca2+]i = 20 +/- 5 nM, n = 11); 2) the dDAVP response was not altered by the specific OT antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine,4-threonine, 8-ornithine,9 tyrosylamide]vasotocin [d(CH2)5(1),O-Me-Tyr2,Thr4,Tyr-NH2(9)]OVT; 3) it was insensitive to V1 antagonists but was totally blocked by the V1/V2 antagonist [d(CH2)5(1),O-Et-Tyr2,Val4]AVP ([delta[Ca2+]i = 18 +/- 4 nM, n = 6). These results indicate that in IMCD AVP increases [Ca2+]i via both V1 and V2 receptors. [Ca2+]i variations due to V2 receptors involve a mechanism independent of adenylate cyclase and coupled to the same intracellular calcium pool as V1 and V2 receptors. PMID- 8342614 TI - Role of muscarinic receptors in renal response to acetylcholine. AB - Renal arterial infusion of acetylcholine (ACh) (40 micrograms/min) in control dogs produced an ipsilateral increase in renal plasma flow (RPF) and in sodium excretion (UNaV) without a change in glomerular filtration rate (GFR). The increase in RPF and UNaV was maintained during the infusion of ACh. In indomethacin (Indo)-treated dogs (5 mg/kg) ACh produced a transient rise in RPF and UNaV, followed by a progressive decline in RPF and UNaV. The profound renal vasoconstriction was accompanied by a decline in GFR. To determine the role of the muscarinic receptor in the renal vasodilation and in vasoconstriction produced by ACh in Indo-treated dogs, atropine at 6, 60, and 600 micrograms/min was infused into the renal artery before and during the infusion of ACh. In Indo treated dogs, all dosages of atropine prevented renal vasoconstriction by ACh. Renal arterial infusion of atropine at 600 micrograms/min completely inhibited the renal vasodilation produced by ACh. Atropine infused at 60 micrograms/min partially inhibited, whereas 6 micrograms/min atropine failed to inhibit, the renal vasodilation produced by ACh. Our data suggest that the renal vasodilator and vasoconstrictor effects of ACh in Indo-treated dogs are mediated by two separate types of muscarinic receptors. PMID- 8342615 TI - Hepatocyte growth factor may function as a renotropic factor for regeneration in rats with acute renal injury. AB - Hepatocyte growth factor (HGF), a potent mitogen for mature hepatocytes, possesses mitogenic and morphogenic activities for renal epithelial cells. To examine the renotropic function of HGF, we investigated the expression of HGF mRNA and HGF activity in the rat kidney after acute renal failure. When acute renal failure was induced by ischemia or by HgCl2 administration, a DNA synthesis occurred predominantly in the renal tubular cells located in the outer medulla with a peak at 48 h after the treatments. In both renal injuries, HGF mRNA in the kidney increased markedly, reaching a maximum 6 to 12 h after the treatments. HGF activity in the kidney also increased to three- to fourfold higher level than the normal level at 12 h after ischemic treatment or HgCl2 administration. In situ hybridization and immunohistochemical analysis indicated that both HGF mRNA and HGF protein were expressed in renal interstitial cells, presumably endothelial cells and macrophages, but not in tubular epithelial cells. In addition, HGF activity in the plasma of rats with renal ischemia or HgCl2 administration rapidly increased, reaching a maximum at 6 h after the treatment. One week after these injuries, HGF mRNA and HGF activity reverted to normal levels, and renal tubular cell regeneration ceased. Moreover, intravenous injection of human recombinant HGF into mice with acute renal failure caused by HgCl2 administration stimulated DNA synthesis of renal tubular cells in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342616 TI - Extrahepatic lipogenesis contributes to hyperlipidemia in the analbuminemic rat. AB - Hepatic lipid and apolipoprotein synthesis is increased in the nephrotic syndrome. Catabolism of triglyceride-rich lipoproteins is impaired in nephrotic syndrome but not in rats with hereditary analbuminemia (NA), suggesting that lipid synthesis should be increased by analbuminemia in the absence of proteinuria. In this study the rate of cholesterol and fatty acid synthesis in liver and extrahepatic tissue was measured in female NA and control Sprague Dawley (SD) rats to determine whether lipid synthesis was indeed increased in isolated analbuminemia and to identify the site(s) of increased lipogenesis. We also measured the concentrations of apolipoproteins (apo) AI, B, and E in plasma, as well as the levels of the respective mRNAs in liver. Plasma cholesterol, triglycerides, and apo AI, B, and E were all increased severalfold in the NA rat (P < 0.001). Although liver apolipoprotein mRNA content was significantly increased (P < 0.001) for apo AI (643%), B (273%), and E (299%), 3-hydroxy-3 methylglutaryl-coenzyme A reductase activity in liver microsomes and hepatic cholesterol synthesis were not significantly increased in the NA rats. Hepatic fatty acid synthesis and intestinal cholesterol synthesis were not increased in the NA rats. Surprisingly, intestinal fatty acid synthesis was elevated by 60% (P < 0.01). The NA rats demonstrated approximately fourfold increases in the incorporation of 3H2O into circulating cholesterol and fatty acids (P < 0.001). A 56% increase in the synthesis of total nonsaponifiable lipid was found in the extravisceral carcass (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342617 TI - Ion concentration changes in renal cells during regulatory volume decrease. AB - Electron-probe microanalysis was employed to follow ion concentration changes during regulatory volume decrease. The measurements were performed on isolated tubule bundles, which were dissected from medullary rays of New Zealand White rabbit kidneys. Cell swelling and subsequent regulatory volume decrease were induced by incubating the bundles in 190 mosM medium; control bundles were incubated in 290 mosM medium. Under both conditions, the detectable ions accounted for approximately 80% of the intracellular osmolarity. All cells lost significant amounts of Na, K, and Cl during cell volume regulation. While in the proximal straight tubule more than one-half of the ions lost were Na and Cl, in principal and intercalated cells of the cortical collecting duct and in the thick ascending limb the losses of Na and Cl played only a minor role. The efflux of Na and K greatly exceeded the Cl efflux, suggesting the loss of an additional undetectable anion (bicarbonate). Separate measurements in the nucleus, cytoplasm, and several cellular organelles revealed some inhomogeneity of the subcellular ion distribution. PMID- 8342618 TI - Osmotically sensitive renin release from permeabilized juxtaglomerular cells. AB - Renin secretion from juxtaglomerular (JG) cells is sensitive to external osmolality in a way that has been suggested to depend either on cellular volume or on effects on secretory granules. To distinguish between these possibilities, a technique for permeabilization of JG cell membranes was developed. Rat glomeruli with attached JG cells were isolated and permeabilized by 20 microM digitonin for 12 min and followed by continuous exposure to 2 microM digitonin. Experiments on proximal tubules showed that cellular volume was unaffected by changes in external sucrose concentration after a similar permeabilization procedure. With permeabilized JG cells the following changes in osmolality were tested (in mM sucrose): +90 (n = 6), +60 (n = 5), +30 (n = 6), +15 (n = 6), -15 (n = 5), -30 (n = 6), -60 (n = 6), and -90 (n = 6). With nonpermeabilized cells similar experiments were done with changes of +90 (n = 7), +30 (n = 4), -30 (n = 4), and -90 (n = 6) mM sucrose. Increases in osmolality caused inhibition of renin release, whereas decreases stimulated secretion. Within +/- 10% variations in osmolality there were no differences between the responses in permeabilized and intact cells, whereas the responses with larger changes were less in the permeabilized cells. Increase or decrease in urea concentration by 30 mM did not affect renin release. Thus water fluxes can influence renin release by a mechanism that is independent of cell volume. PMID- 8342619 TI - Effects of rC5a on the circulation of normal and split hydronephrotic rat kidneys. AB - Systemic release of complement-derived anaphylatoxin C5a is suggested to be involved in the pathogenesis of renal failure during endotoxic or severe traumatic shock. In the present study we analyzed renal hemodynamic effects of recombinant human complement 5a (rC5a) and examined whether these effects are mediated by the secondary release of other inflammatory mediators. Intravenous infusion of rC5a (0.5 micrograms/min) in thiobarbital-anesthetized rats decreased renal blood flow (RBF) by 20 and 34% after 20 and 60 min, respectively. Glomerular filtration rate (GFR) was reduced by 45%, whereas filtration fraction and blood pressure were not significantly changed by rC5a. Hematocrit (Hct) increased by 11%, whereas white blood cell count decreased by 40%. Renal rC5a effects were completely inhibited by the competitive leukotriene D4/E4 antagonist ICI-198615, whereas the competitive thromboxane A2 (TxA2) antagonist daltroban only partly reversed rC5a effects on RBF and GFR. The competitive platelet activating factor (PAF) antagonist L-695989 did not influence renal or systemic rC5a effects. These results point to an rC5a-mediated synthesis and release of cysteinyl leukotrienes and TxA2, whereas PAF does not seem to be released after intravenous rC5a in rats. To determine the cellular source of cysteinyl leukotriene synthesis, rats were depleted of polymorphonuclear cells (PMN) by intraperitoneal injection of anti-rat PMN antibodies, which abrogated renal and systemic hemodynamic rC5a effects, suggesting that PMN participate in the synthesis and release of cysteinyl leukotrienes. The exact localization of renovascular rC5a effects was performed on the model of the split hydronephrotic rat kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342620 TI - Neural mechanism underlying basilar arterial constriction by intracisternal L-NNA in anesthetized dogs. AB - Basilar arterial diameters were angiographically measured in anesthetized dogs in which systemic blood pressure and heart rate were also monitored. Injections of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, into the cisterna magna produced a significant, persistent decrease in arterial diameter, the effect being reversed by intracisternal injections of L-arginine. The vasoconstrictor effect of L-NNA was diminished in dogs treated with hexamethonium. On the other hand, treatment with phentolamine in a dose sufficient to lower blood pressure to a level similar to that attained with hexamethonium did not inhibit, but rather potentiated, the effect of intracisternal L-NNA. Nicotine injected into the vertebral artery significantly dilated the basilar artery. The effect was abolished by treatment with L-NNA applied intracisternally, the inhibition being reversed by the addition of L-arginine. Systemic blood pressure and heart rate were not altered by intracisternally applied L-NNA and L-arginine. These findings support the hypothesis that basilar arterial constriction caused by intracisternal L-NNA is associated with a suppression of NO synthesis in nitroxidergic nerves innervating the cerebroarterial wall rather than an elimination of basal release of NO from the endothelium. Functional importance of nitroxidergic vasodilator innervation in cerebral arteries in vivo is thus clarified. PMID- 8342621 TI - Endotoxin induces metabolic dysregulation of vascular tone. AB - The goals of this study were to determine 1) if endotoxin alters vascular responsiveness to metabolic stimuli and 2) if the decompensatory loss of skeletal muscle vascular tone that occurs during endotoxemia is induced by increased muscle metabolism. Vascularly isolated and denervated canine gracilis muscles were perfused in situ at a constant flow. In the first set of experiments, gracilis muscle O2 extraction (MVO2) and perfusion pressure were continuously measured during direct electrical stimulation of the muscle mass. Endotoxemia was induced by a 30-min intravenous infusion of Escherichia coli endotoxin (2 mg/kg), and the stimulations were repeated 60 min postendotoxemia. Compared with the nonendotoxic control, the endotoxemic muscle stimulation resulted in a decreased MVO2, and the vascular response (dilation) was potentiated. In the second set of experiments, the MVO2 of the experimental muscle (GMe) was lowered by cooling the temperature of the blood perfusing the muscle to 22-24 degrees C while maintaining the temperature of the contralateral control muscle (GMc) at 34-35 degrees C. After the administration of endotoxin, arterial pressure fell and the GMc showed a progressive increase in MVO2 and loss of vascular tone (decompensation). Coincidently, the GMe showed no significant change in MVO2 and did not vasodilate. The major findings of this study are 1) endotoxin induces the vasculature to become more reactive to metabolic vasodilation, and 2) the decompensatory vasodilation typically observed during endotoxemia can be abolished if MVO2 (i.e., metabolism) is kept low by cooling the muscle. The data suggest that endotoxemia increases vascular sensitivity to vasodilatory metabolites, which allows local mechanisms to dominate extrinsic nonneural forces and control vascular tone, thus inducing vasodilation. PMID- 8342622 TI - Ca(2+)-dependent fluorescence transients and phosphate metabolism during low-flow ischemia in rat hearts. AB - To determine whether cytosolic free calcium ([Ca2+]i) rises during low-flow ischemia and to determine the mechanisms responsible for contractile dysfunction, isolated rat hearts were studied during graded reductions of coronary flow. Indo1 fluorescence at 385- and 456-nm wave-lengths (F385/456) was used as an index of [Ca2+]i. 31P-magnetic resonance spectroscopy (MRS) was used to measure free energy of ATP hydrolysis (delta GATP), intracellular pH (pHi), and Pi in parallel experiments to determine whether these factors may be responsible for increasing diastolic [Ca2+]i or altering the [Ca2+]i-pressure relationship. When coronary flow was reduced to 20 and 10% of control, diastolic F385/456 increased by 14 +/- 3 and 39 +/- 5%, respectively. Although developed pressure markedly decreased when coronary flow was reduced, there was no change of the F385/456 transient amplitude (systolic minus diastolic). During low-flow ischemia there was a significant decrease of delta GATP and increase of Pi that may lead to increased [Ca2+]i. Furthermore, there was a close inverse relationship between Pi and developed pressure, suggesting that Pi is an important regulator of contractility. PMID- 8342623 TI - Regulation of diaphragmatic oxygen uptake by endothelium-derived relaxing factor. AB - The role of endogenous nitric oxide (NO) in the regulation of phrenic blood flow (Qphr) and O2 consumption (VO2) of the in situ isolated left hemidiaphragms was assessed in two groups of anesthetized, mechanically ventilated dogs. Saline was infused into the phrenic artery for 20 min in one group, whereas N omega-nitro-L arginine (L-NNA, 6 x 10(-4) M) was infused in the other (L-NNA) group. Qphr and diaphragmatic VO2 were measured at rest and during 2 min of continuous 3-Hz stimulation of the left phrenic nerve. The animals were progressively hemorrhaged, and the measurements were repeated at various arterial pressures (Pa). For the resting diaphragm, Qphr at a mean Pa of 145 mmHg was lower in the L NNA group than in the saline group; however, diaphragmatic VO2 values were similar in both groups. Qphr decreased with the decline in Pa in both groups, but O2 extraction ratios obtained at mean Pa of 25-45 mmHg were similar in both groups (71 vs. 73%). For the contracting diaphragm, Qphr and diaphragmatic VO2 values at a given Pa were lower in the L-NNA group than in the saline group (except at mean Pa < 75 mmHg). O2 extraction ratios obtained at a given Pa were similar in both groups. We concluded that 1) EDRF inhibition limits diaphragmatic blood flow both at rest and during 3-Hz stimulation; 2) diaphragmatic O2 extraction is unaffected by EDRF inhibition; and 3) the effect of EDRF release on diaphragmatic VO2 is dependent on the level of metabolic demands. PMID- 8342624 TI - Adenosine stimulates proliferation of human endothelial cells in culture. AB - The effect of adenosine on proliferation of human endothelial cells was investigated by adding adenosine to the medium of cultures derived from human umbilical veins. Cell counts on cultures grown in 10 microM adenosine for 4-7 days were 41-53% greater than counts from control cultures. In contrast, 10 microM adenosine had no effect on growth of a human fibroblast cell strain (IMR 90). Neither inosine nor 2',5'-dideoxyadenosine influenced endothelial cell growth at concentrations of 0.1 or 10 microM. Addition of adenosine deaminase abolished the proliferative effect of added adenosine and inhibited proliferation by 16% in control cultures, suggesting that endogenous adenosine may enhance proliferation in culture. The adenosine receptor antagonist, 8 phenyltheophylline, at 0.1 and 1.0 microM blocked the enhanced proliferation caused by 10 microM adenosine. Addition of 10 microM adenosine enhanced DNA synthesis in endothelial cell cultures as indicated by an increased incorporation of [3H]thymidine into acid-insoluble cell material. The results indicate that addition of physiological concentrations of adenosine to human umbilical vein endothelial cell cultures stimulates proliferation, possibly via a surface receptor, and suggest that adenosine may be a factor for human endothelial cell growth and possibly angiogenesis. PMID- 8342625 TI - Ontogeny of Big endothelin-1 effects in newborn piglet pulmonary vasculature. AB - Endothelin-1 (ET-1), a 21-amino acid peptide produced by endothelial cells, results from the cleavage of preproendothelin, generating Big ET-1, which is then cleaved by the ET-converting enzyme (ECE) to form ET-1. Big ET-1, like ET-1, is released by endothelial cells. Big ET-1 is equipotent to ET-1 in vivo, whereas its vasoactive effects are less in vitro. It has been suggested that the effects of Big ET-1 depend on its conversion to ET-1. ET-1 has potent vasoactive effects in the newborn pig pulmonary circulation, however, the effects of Big ET-1 remain unknown. Therefore, we studied the effects of Big ET-1 in isolated perfused lungs from 1- and 7-day-old piglets using the ECE inhibitor, phosphoramidon, and the ETA receptor antagonist, BQ-123Na. The rate of conversion of Big ET-1 to ET-1 was measured using radioimmunoassay. ET-1 (10(-13) to 10(-8) M) produced an initial vasodilation, followed by a dose-dependent potent vasoconstriction (P < 0.001), which was equal at both ages. Big ET-1 (10(-11) to 10(-8) M) also produced a dose dependent vasoconstriction (P < 0.001). The constrictor effects of Big ET-1 and ET-1 were similar in the 1-day-old, whereas in the 7-day-old, the constrictor effect of Big ET-1 was less than that of ET-1 (P < 0.017).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342626 TI - Differences in EDNO contribution to arteriolar diameters at rest and during functional dilation in striated muscle. AB - This study was designed to determine the physiological role of endothelium dependent nitric oxide (EDNO) in the control of arteriolar diameter during rest and muscle stimulation. Diameters of first-, second-, and third-order arterioles in the superfused hamster cremaster muscle were measured before and throughout 1 min of field stimulation before and after inhibition of EDNO release. ENDO inhibition by intravenous N omega-nitro-L-arginine methyl ester (L-NAME) significantly attenuated the arteriolar vasodilation in response to 1 microM acetylcholine. First-order arterioles averaged 65 +/- 5 microns at rest and dilated to 86 +/- 6 microns during muscle stimulation (n = 9), second-order arterioles averaged 45 +/- 6 microns and dilated to 72 +/- 3 microns during muscle stimulation (n = 6), with third-order arterioles averaging 29 +/- 2 microns, and dilating to 53 +/- 3 microns during muscle stimulation (n = 7). EDNO inhibition significantly decreased both the resting diameter of first-order arterioles (57 +/- 4 microns) and functional dilation (68 +/- 3 microns; P < 0.05). EDNO inhibition had no effect on the resting diameter of second-order arterioles (45 +/- 5 microns) yet significantly attenuated the functional dilation (64 +/- 4 microns; P < 0.05). EDNO inhibition had no effect on either the resting diameter of third-order arterioles (30 +/- 2 microns) or the functional dilation (49 +/- 2 microns).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342628 TI - Responses of cerebral arterioles in diabetic rats to activation of ATP-sensitive potassium channels. AB - The goal of this study was to determine whether responses of pial arterioles to activation of ATP-sensitive potassium channels are altered during diabetes mellitus. We measured changes in diameter of pial arterioles in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg ip; studied 3-4 mo after streptozotocin) in response to RP52891, an activator of ATP-sensitive potassium channels. RP52891 (1.0 microM) dilated pial arterioles in nondiabetic rats by 16 +/- 1% but constricted pial arterioles in diabetic rats by 2 +/- 2% (means +/- SE; P < 0.05 vs. response in nondiabetic rats). Dilatation of pial arterioles in nondiabetic rats in response to RP52891 was inhibited by glibenclamide (1.0 microM) but was not altered by NG-monomethyl-L-arginine (1.0 microM), apamin (0.1 microM), or charybdotoxin (50 nM). Thus dilatation of pial arterioles in response to RP52891 appears to be due to activation of ATP sensitive potassium channels and does not involve nitric oxide or calcium activated potassium channels. To determine whether impaired dilatation of pial arterioles in response to RP52891 in diabetic rats was related to a nonspecific effect of diabetes mellitus on vasodilatation, we measured diameter of pial arterioles in nondiabetic and diabetic rats in response to nitroglycerin. Nitroglycerin (1.0 microM) dilated pial arterioles by 12 +/- 1% in nondiabetic rats and 16 +/- 2% in diabetic rats (P > 0.05). Thus impaired dilatation of pial arterioles in diabetic rats in response to RP52891 also is not related to a nonspecific effect of diabetes mellitus on vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342627 TI - Endothelium, vasopressin receptors, and resistance to DOCA-salt hypertension. AB - Mesenteric artery rings from Wistar and Wistar-Furth rats subcutaneously treated with deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water were used to measure endothelial modulation of contractile sensitivity and vasopressin receptor function and affinity. DOCA-salt hypertension reduced contractile sensitivity to arginine vasopressin (AVP) and did not affect contractile sensitivity to norepinephrine in arteries from Wistar rats. Endothelial removal caused a threefold increase in contractile sensitivity to AVP and norepinephrine in DOCA-salt hypertensive Wistar rats. In Wistar-Furth rats, DOCA-salt treatment did not affect contractile sensitivity to AVP, lysine vasopressin, oxytocin, and norepinephrine or the affinity of the vasopressin receptor for agonists or antagonists. Removal of endothelium did not affect vasopressin contractile sensitivity but caused a 15-fold increase in contractile sensitivity to norepinephrine in untreated or DOCA-salt-treated Wistar-Furth rats. These data show that reduced vasopressin receptor function and increased endothelial function that compensate for increased contractile sensitivity in arteries from DOCA-salt hypertensive Wistar rats are not the cause of resistance of DOCA-salt treated Wistar-Furth rats to the development of enhanced contractile sensitivity and hypertension. PMID- 8342629 TI - 5-Hydroxytryptamine dominates over thromboxane A2 in reducing collateral blood flow by activated platelets. AB - Intra-aortic infusion of collagen (100 micrograms/kg in 1 min) elicited an extensive platelet activation and transient but marked reductions of blood flow and increases of peripheral vascular resistance, both responses being more pronounced in collaterals than in normal arterial beds in feline hind legs. Blockade of 5-hydroxytryptamine (5-HT) subtype 2 (5-HT2) receptors for 5-HT (ketanserin or ritanserin, 0.63 mg/kg iv, -10 min) or amine depletion (reserpine, 0.1 mg/kg im, -10 days, + parachlorophenylalanine 100 mg/kg sc daily for 3 days), but not cyclooxygenase inhibition (indomethacin, 5 mg/kg iv) or thromboxane (Tx) A2/prostaglandin endoperoxide receptor antagonism (sulotroban, 2.5 mg/kg iv), largely prevented the collagen-induced perfusion defect without interfering substantially with the platelet activation process. TxA2 synthase inhibition, alone (dazoxiben, 5 mg/kg iv) or combined with TxA2-prostaglandin endoperoxide receptor antagonism (ridogrel, 2.5 mg/kg iv), partially reduced the collagen induced perfusion defect and limited to a similar extent the initial platelet aggregation and release of 5-hydroxyindoles and TxB2 while increasing plasma levels of prostacyclin. These results suggest that platelet-derived 5-HT dominates over TxA2 in reducing blood flow in collateral-dependent tissue of the cat hindlimb. PMID- 8342630 TI - Induction of heat shock response leads to apoptosis in endothelial cells previously exposed to endotoxin. AB - The homeostatic response of complex eukaryotes to the challenge of environmental stress includes the induction of several programs of gene expression; among them are those for the acute phase genes and those for the heat shock genes. In some systems, the heat shock response, which is often elicited by more severe stimuli, preempts the acute phase response, which is seen in response to less severe challenges, as well as constitutive gene expression. Nevertheless, each response appears to provide a natural selective advantage for survival of the organism in a toxic environment. However, when cultured porcine endothelial cells were exposed first to a nonlethal level of bacterial endotoxin lipopolysaccharide (LPS), an inducer of the acute phase response, and then, simultaneously to standard stimuli, which normally elicit a salutary heat shock response, the cells died manifesting a pattern of DNA fragmentation (nucleolysis) characteristic of programmed cell death (apoptosis). The treatment of LPS-exposed cells with cycloheximide to block protein synthesis reproduced the lethal apoptosis that had been elicited by the induction of heat shock gene expression. Therefore, the preemption of other programs of stress gene expression by the prioritized expression of heat shock genes is associated with apoptosis. PMID- 8342631 TI - Contribution of prostaglandins to exercise-induced vasodilation in humans. AB - It has been postulated that endothelial release of prostaglandins contributes to exercise-induced vasodilation of skeletal muscle arterioles. To test this hypothesis, 12 normal subjects underwent brachial arterial and venous catheter insertion and instrumentation of their forearm to measure plethysmographic forearm blood flow. Forearm blood flow and arterial and venous 6 ketoprostaglandin F1 alpha (PGF1 alpha) and prostaglandin E2 (PGE2) were then measured during two levels of wrist flexion exercise (0.2 and 0.4 W). In nine of the subjects, exercise was repeated after intra-arterial infusion of indomethacin (0.3 mg/100 ml forearm vol). Exercise increased forearm blood flow (2.0 +/- 0.2 to 12.1 +/- 1.1 ml.min-1.100 ml-1) and forearm release of PGF1 alpha (162 +/- 28 to 766 +/- 193 pg.min-1.100 ml-1) and PGE2 (26 +/- 6 to 125 +/- 46 pg.min-1.100 ml-1) (all P < 0.05). Indomethacin virtually abolished forearm prostaglandin release and reduced forearm blood flow at rest (2.2 +/- 0.2 to 1.7 +/- 0.2 ml.min 1.100 ml-1), at 0.2 W (6.3 +/- 0.7 to 5.4 +/- 0.7 ml.min-1.100 ml-1), and at 0.4 W (12.2 +/- 1.5 to 10.3 +/- 1.3 ml.min-1.100 ml-1) (all P < 0.02). These data suggest that release of vasodilatory prostaglandins contributes to exercise induced arteriolar vasodilation and hyperemia in skeletal muscle. PMID- 8342632 TI - Nitric oxide attenuates cardiac myocyte contraction. AB - Cardiac muscle fibers have microvessels in close proximity, the distance from the nearest capillary being no greater than 8 microns. We performed experiments on isolated, electrically stimulated, contracting guinea pig cardiac myocytes to test whether NO from endothelium or nitrovasodilators or directly superfused in solution might affect myocyte contractility. In endothelium-myocyte coculture experiments, 10(-7) M bradykinin reduced myocyte shortening by 11 +/- 3.5%. This effect was abolished in the presence of NG-nitro-L-arginine methyl ester and was unaffected by indomethacin. Sodium nitroprusside, but not organic nitrovasodilators, reduced myocyte contraction amplitude by 23% at 3 x 10(-5) M. This effect was reversed by methylene blue. Superfusion with NO solution had an effect similar to sodium nitroprusside, as did exposure to 8-bromoguanosine 3',5' cyclic monophosphate. Thus the present study shows that cardiac myocyte contraction is attenuated by NO, which appears to act via production of guanosine 3',5'-cyclic monophosphate within the myocytes. Because cardiac myocytes in vivo are in such close proximity to endothelium, the effects of endothelial products on cardiac myocyte contractility may be important in myocardial function. PMID- 8342633 TI - Normal and hypertrophied senescent rat heart: mechanical and molecular characteristics. AB - The energetics of the senescent (S) rat heart and the mechanisms by which it adapts to pressure overload have been investigated by simultaneous cardiac mechanical, energetic, and molecular biological studies. Compared with young adult (YA), S papillary muscles had an improved economy of contraction since the curvature (G) of Hill's (Proc. R. Soc. Lond. B. Biol. Sci. 126:136-195, 1938) hyperbola was increased (S, 1.93 +/- 0.13; YA, 1.60 +/- 0.07, P < 0.05). In addition, the maximum unloaded shortening (Vmax) and relengthening velocities were both reduced in S. In parallel, both alpha-myosin heavy chain (MHC) and sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) mRNA contents were reduced (-30 and -28%, respectively), whereas beta-MHC mRNA was increased (+91%). The active tension (S, 40.0 +/- 2.6; YA, 50.1 +/- 2.5 mN/mm2, P < 0.01) was depressed although the active force remained unchanged (S, 52.0 +/- 4.0; YA, 47.5 +/- 2.5 mN). Pressure overload in senescent deoxycorticosterone acetate (DOCA)-salt rats induced a left ventricular hypertrophy (+43%) and a further decrease in both Vmax (S, 2.81 +/- 0.10; DOCA-salt, 2.55 +/- 0.13 initial length corresponding to peak of length-active curve/s, P < 0.05) and alpha-MHC mRNA ( 30%) content. Senescence modifies mechanics and gene expression in a way similar to pressure overload. During senescence, an additional overload induces left ventricular hypertrophy and attenuates Vmax without worsening the economy of the contraction. PMID- 8342634 TI - Presynaptic effects of epinephrine on norepinephrine release from cardiac sympathetic nerves in dogs. AB - The possible functional role of tissue epinephrine in the modulation of norepinephrine release from cardiac sympathetic nerve endings in anesthetized dog was investigated. Observations were carried out under control conditions and after a short- (10 min) and long-term (180 min) epinephrine infusion (92 ng.kg 1.min-1). An increase in the stimulation-induced release of norepinephrine after intravenous administration of a selective beta 2-agonist (fenoterol, 0.5 micrograms/kg) indicated the presence of the beta 2-facilitatory mechanism. Furthermore, the facilitatory effect of fenoterol was inhibited by intravenous administration of a selective beta 2-antagonist (ICI 118551, 1 mg/kg). Short-term epinephrine infusion did not facilitate the stimulation-induced release of norepinephrine, when tissue epinephrine content in the left ventricle was increased 1.5-fold, without, as well as with, alpha 2-blockade (yohimbine, 0.3 mg/kg). However, stimulation-induced release of norepinephrine from the myocardium was significantly potentiated in animals in which tissue epinephrine in the left ventricle was greatly increased (5.6-fold) by a prolonged infusion of epinephrine (180 min). It is concluded that a facilitatory mechanism mediated by presynaptic beta 2-adrenoceptors is present in cardiac sympathetic nerve endings of the dog. Some of our observations support the hypothesis that this mechanism may be influenced by locally released epinephrine and, thus, by tissue epinephrine content. PMID- 8342635 TI - Age-associated increase in rat cardiac opioid production. AB - Several lines of evidence suggest that opioid peptide production in the heart may increase during aging from adulthood through senescence. We tested the hypothesis that cardiac opioid peptides and preproenkephalin (PNK) mRNA would increase with advancing age. Ventricles and atria from male Wistar rats, aged 2, 6, 18, and 22 24 mo of age, were acid extracted and assayed for methionine enkephalin (ME) and leucine enkephalin (LE). Total RNA was extracted from hearts of age-matched rats and probed for PNK mRNA by Northern blot analysis using a cDNA probe. ME and LE peptides were significantly elevated with advancing age in both ventricles [P < 0.001; by analysis of variance (ANOVA)]. Ventricular ME concentration exhibited a biphasic increase with approximately twofold higher peaks at 6 and 22-24 mo of age compared with the 2 mo value of 1.04 +/- 0.05 (SE) pmol/g wet wt. In contrast, ventricular LE concentration was largely unchanged until 22-24 mo of age when it increased approximately threefold over the 2-mo value of 2.19 +/- 0.14 pmol/g wet wt. Left ventricular PNK mRNA increased approximately fivefold between 2 and 18 mo of age (P < 0.01; ANOVA). Thus both enkephalins and the mRNA coding for them were increased in hearts of older vs. younger rats. Because opioid receptor stimulation can negatively modulate several characteristics of cardiac myocyte contraction, these results may have important functional implications for the senescent heart. PMID- 8342636 TI - Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilation of normal rat arterioles. AB - Arteriolar dilation to endothelium-derived relaxing factor (EDRF) is suppressed early in diabetes mellitus. The purpose of this study was to determine whether acute exposure to a hyperglycemic media can suppress EDRF function of normal arterioles. Dilation of intestinal arterioles to iontophoretically applied acetylcholine (ACh) and nitroprusside was measured in normoglycemic rats before and after 1 h of topical exposure to isotonic solutions containing D-glucose concentrations of 200, 300, and 500 mg/100 ml. Exposure to a D-glucose concentration of 200 mg/100 ml had no effect on vasodilation to ACh. D-Glucose concentrations of both 300 and 500 mg/100 ml caused significant suppression of the responses: for example, at the approximate 50% effective dosage (100 nA), the dilatory response was decreased by 60% at a D-glucose concentration of 300 mg/100 ml and 55% at a D-glucose concentration of 500 mg/100 ml. Responses to nitroprusside were not significantly (P < 0.05) impaired after exposure to D glucose concentrations of 200, 300, or 500 mg/100 ml. Exposure to an isotonic L glucose concentration of 500 mg/100 ml for 1 h had no significant (P > 0.05) effect on responses to ACh. Pretreatment with superoxide dismutase, catalase, indomethacin, or meclofenamic acid preserved EDRF-mediated vasodilation during exposure to a D-glucose concentration of 500 mg/100 ml at almost all the ACh dosages tested. These results indicate that oxygen radicals formed in part by increased eicosanoid synthesis during exposure to D-glucose hyperglycemia interfere with the EDRF mechanism before its action on the microvascular smooth muscle. PMID- 8342638 TI - Relationship of arterial compliance to baroreflex function in hypertensive patients. AB - The objectives of this study were to determine whether carotid arterial compliance is reduced in patients with hypertension and to assess whether reduced arterial compliance is related to abnormal arterial baroreflex function. Accordingly, concurrent measurements of carotid arterial diameter (via computerized high resolution B-mode ultrasonography) and blood pressure were made to determine carotid arterial compliance in 23 normotensive and 16 age-matched hypertensive patients. In addition, arterial baroreflex function was assessed in 12 of the normal subjects and nine of the hypertensive patients by measuring the infusions of nitroprusside and phenylephrine. Compared with the normotensive subjects, the patients with hypertension had reduced compliance (5.9 +/- 0.7 vs. 16.6 +/- 1.8 10(-7) m2/kPa, mean +/- SE, P < 0.001). The baroreflex slope relating the change in R-R interval to the change in systolic blood pressure during the drug infusions was less in the hypertensive than normotensive subjects (12.3 +/- 2 vs. 18.9 +/- 2 ms/mmHg, P < 0.05). Consequently, when both normotensive and hypertensive subjects were considered, there was a significant correlation between the baroreflex slope and compliance (r = 0.53, P < 0.05). However, there was no correlation between the baroreflex slope and compliance within either the normotensive group (r = 0.04, P = NS) or the hypertensive group (r = 0.43, P = NS) when analyzed separately. There was a significant correlation between age and compliance (r = -0.48, P < 0.01) but not between age and baroreflex function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342637 TI - Differential blockade of central effects of angiotensin II by AT2-receptor antagonists. AB - In conscious, chronically instrumented, male Long-Evans rats, we showed previously that central administration (intracerebroventricular) of the AT1 receptor antagonist EXP-3174 (1 microgram) caused a rapid-onset marked, but transient, blockade of the regional hemodynamic responses to intracerebroventricular angiotensin II (ANG II). In contrast, the AT2-receptor antagonist PD-123319 (80 micrograms) caused a slow-onset, but marked and persistent, antagonism of the effects of intracerebroventricular ANG II. In the present study we attempted to mimic the actions of PD-123319 by giving a supramaximal dose of EXP-3174 (10 micrograms), and we also assessed the effects of PD-123177 (80 micrograms), an AT2-receptor antagonist that differs from PD 123319 only by a dimethyl group. The higher dose of EXP-3174 did not exert prolonged antagonistic effects against responses to intracerebroventricular ANG II, and PD-123177 was without inhibitory effects in this model. The results indicate important functional differences between putative AT2-receptor antagonists, when assessed in vivo, that are not apparent from binding studies. PMID- 8342639 TI - Angiotensin II increases cardiac protein synthesis in adult rat heart. AB - This study examined the direct effect of angiotensin II (ANG II) on cardiac muscle atrophy previously observed in the denervated rat heart. Rats with transplanted hearts were infused with normal saline (1 microliter/h) or a subpressor dose of ANG II dissolved in saline (3 micrograms.kg-1.h-1) for 1 wk. Left ventricular (LV) mass of transplanted hearts decreased by 29 and 18% in the saline-infused and ANG II-infused groups, respectively (P < 0.05). Total LV protein synthesis of the transplanted heart was 1.4 +/- 0.1 mg.LV-1.day-1 in the saline compared with 2.2 +/- 0.2 mg.LV-1.day-1 in the ANG II (P < 0.05) group. Heart rate and carotid systolic arterial pressures were not affected by ANG II infusion, and the decrease in alpha-myosin heavy chain normally observed in this model was unchanged between the two groups (61 +/- 3 and 66 +/- 1%, saline vs. ANG II). These data demonstrate that ANG II increases total cardiac protein synthesis in the adult heart, leading to an attenuation in cardiac atrophy. The failure of ANG II to prevent the shift from alpha- to beta-myosin heavy chain may be related to its lack of an effect on heart rate, since other interventions that affect myosin isoenzyme distribution also increase heart rate. PMID- 8342640 TI - Effect of upright tilt on ventricular/vascular coupling in chronically instrumented primates. AB - Studies of the hydraulic loading conditions on the heart in humans, especially pulsatile load, have primarily been limited to the supine state. Therefore, we have chosen a nonhuman primate model, the baboon, to assess left ventricular/vascular coupling in both supine and upright positions. Primate subjects were studied by catheterization under sedation and then after surgical implantation of transducers. This allowed the evaluation of postural stress in the chronically instrumented conscious baboon and then after light dissociative doses of ketamine. Basic hemodynamic variables were evaluated for baboons in supine and upright positions. Fourier analysis was applied to aortic pressure and flow to obtain input and characteristic impedance and the ratio of pulsatile (Wp) to total (Wt) left ventricular power (Wp/Wt). The aortic reflected, or backward, pressure was also calculated. Peripheral resistance increased (P = 0.01) and reflected pressure decreased (17.74 +/- 1.50 vs. 15.21 +/- 2 mmHg; P < 0.01) in upright subjects. Characteristic impedance and Wp/Wt were unchanged. Postoperatively, peripheral resistance increased (2,651 +/- 311 vs. 3,667 +/- 276; P < 0.05) and mean power and Wt decreased (P < 0.01) without changes in reflected pressure. All variables were unchanged after light dissociative doses of ketamine. Thus there is no significant change in efficiency of left ventricular/vascular coupling formulated in terms of Wp/Wt or input impedance with postural stress. PMID- 8342641 TI - Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia reperfusion. AB - Generation of free radicals during reperfusion after organ ischemia has been implicated in the pathogenesis of ischemic injury. We have previously shown that a combination of intravenous polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT), at a dose of 10,000 U/kg each, is effective in reducing infarct size in a focal cerebral ischemia model in the rat. It is not clear whether PEG-SOD alone is sufficient to reduce ischemic brain injury. In this study we determined the therapeutic efficacy of PEG-SOD and its dose response curve. In a range of 1,000-30,000 U/kg, PEG-SOD exhibited a U-shaped dose-response curve. Only 10,000 U/kg significantly reduced infarct size [control 121 +/- 12 mm3 (mean +/- SE), n = 35; PEG-SOD 95 +/- 10 mm3, n = 36, P < 0.05]. PEG-SOD at the doses tested did not have significant acute hemodynamic effects but had a tendency to improve postischemic hypotension. This beneficial effect of PEG-SOD on blood pressure did not appear to fully account for the treatment effect of PEG-SOD on infarct size. The narrow therapeutic dose range of PEG-SOD in this study and similar findings of SOD in other investigations may contribute to the inconsistent protective effects of SOD preparations in ischemia reperfusion injury in the literature. PMID- 8342642 TI - Activated complement directly modifies the performance of isolated heart muscle cells from guinea pig and rat. AB - The complement system has been implicated in the pathogenesis of cardiovascular disorders including ischemia and atherosclerosis. Selective deposition of C5b-9, the membrane attack complex of complement, has been histochemically documented in human myocardium early after reperfusion of ischemic areas and in infarcted zones. However, functional sequelae of the C5b-9 complex binding to myocardial cells have not been identified. Insertion of C5b-9 complexes into the membrane of other cell types can generate transient changes in membrane permeability in the absence of cell lysis. We demonstrate in beating isolated adult guinea pig and rat cardiac myocytes that human derived C5b-9 can transiently augment in a dose dependent manner both basal cytosolic calcium concentration and calcium transients, resulting in a temporary increase in contractility. If similar changes occur in human heart cells in vivo, they could significantly affect myocardial performance and contribute to functional abnormalities seen in ischemia and other pathological conditions associated with complement activation. PMID- 8342643 TI - Effects of collagenase, elastase, and hyaluronidase on mechanical properties of isolated dog jugular veins. AB - To study the contribution of tissue components to the mechanical properties of veins, pressure-volume relationships were obtained with the cylindrical segments of isolated dog external jugular veins at several levels of longitudinal extension. At each length, the transmural pressure of the segment was raised up to 20 cmH2O and then reduced to 0 cmH2O by increasing and decreasing the intraluminal volume at a constant rate. The longitudinal extension of the venous segments caused a significant reduction in the incremental volume elasticity within the pressure range of 0-2 cmH2O (E0-2) as well as a significant increase of the incremental volume elasticity within 10-20 cmH2O (E10-20). The pressure volume relationships of venous segments were also constructed in the same way after treatment with 1 mg/ml collagenase for 30 min, 0.1 mg/ml elastase for 5 min, or 1 mg/ml hyaluronidase for 60 min. Treatment with collagenase or elastase produced a significant increase of the E0-2. The treatment, however, caused no effect on E10-20. Treatment with hyaluronidase induced no effect on these mechanical parameters but produced a significant attenuation of the extension induced decrease in E0-2. Activation of the venous smooth muscles induced by norepinephrine (10(-4) M) or high-potassium Krebs solution caused a significant decrease of E0-2 as well as a significant increase of E10-20. A complete relaxation of the smooth muscles elicited by Ca(2+)-free Krebs solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (2 mM) caused an increase of E0-2. Mechanical rubbing of the endothelium caused no significant effect on E0-2 and E10-20.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342644 TI - Dynamics of intracellular free Mg2+ changes in a vascular smooth muscle cell line. AB - Intracellular free Mg2+ concentration ([Mg2+]i) has been implicated in the pathogenesis of hypertension. It has been postulated that Mg2+ through its antagonistic effects on intracellular Ca2+ concentration may affect tension and contractility of vascular smooth muscle cells. An established cell line of rat thoracic aorta cells (A10) was cultured on glass cover slips, and [Mg2+]i was determined by fluorescent techniques on single cells with the use of mag-fura-2. Basal [Mg2+]i was 0.52 +/- 0.02 mM (n = 15). Vascular smooth muscle cells were challenged with A23187 plus 5 mM MgCl2 to rapidly elevate [Mg2+]i. [Mg2+]i increased to a peak of 1.03 +/- 0.09 mM within 1-2 s and then quickly declined to below basal levels, 0.30 +/- 0.03 mM, within 45-60 s despite the continued presence of A23187 and external Mg2+. The rapid removal of the Mg2+ challenge to below basal levels suggests the presence of intracellular transport mechanisms, likely in intracellular compartments or organelles. Spatial imaging studies indicated that Mg2+ is heterogeneously distributed within the cell with the greatest variations in the perinuclear region, the area of most cytosolic organelles. Vanadate, an inhibitor of P-type adenosinetriphosphatases, inhibited the removal rate from 10.2 +/- 0.9 to 6.8 +/- 1.0 microM/s. Inhibitors of intracellular Ca2+ mobilization, thapsigargin, dantrolene, and 3,4,5 trimethoxybenzoic acid 8-(diethylamino)octyl ester, inhibited Mg2+ sequestration. Ryanodine and caffeine had no effect on Mg2+ removal. Ruthenium red did not inhibit Mg2+ sequestration, but oligomycin B slowed its removal. These studies demonstrated that [Mg2+]i in vascular smooth muscle cells is carefully controlled by active mechanisms involving intracellular and plasma membrane transporters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342645 TI - Dependence of endothelium-mediated relaxation on oxygen and metabolism in porcine coronary arteries. AB - Hypoxia has major effects on endothelium-dependent relaxation. To further understand the underlying mechanism(s), we investigated the O2 dependence of the endothelium-dependent relaxations elicited by ionophore A-23187 or agonists substance P (SP) or thrombin (TB) in porcine coronary arteries. A-23187 elicits an endothelium-dependent relaxation of KCl- or U-46619-induced contractures that can be described in terms of a rapid and slow phase. The duration of the relaxation was dose dependent. SP (10 nM) and TB (0.1 U/ml) also elicited endothelium-dependent relaxations that were rapid but transient. Hypoxic conditions (95% N2-5% CO2 instead of 95% O2-5% CO2; PO2 < 1%) abolished the A 23187 rapid phase and the SP and TB transient relaxation but not the A-23187 slow phase. Threshold PO2 for the rapid phase was approximately 35 mmHg. Pretreatment with cyanide (5 mM), to inhibit respiration, or 2-deoxy-D-glucose, to inhibit glycolysis, had little effect. Similarly, propranolol (10 microM) or indomethacin (10 microM) had no effect on the relaxation to A-23187, TB, or SP. In contrast, both NO synthesis inhibitors and ouabain blunted all endothelium-dependent relaxations studied. Our results suggest that the rapid relaxations to A-23187, SP, and TB are sensitive to O2 but not mitochondrial respiration. The slow sustained relaxation induced by A-23187, however, is characterized by a sensitivity to O2 that is distinct from that of the rapid phase, yet is dependent on an intact endothelium and is affected by NO synthesis inhibitors. Thus the endothelium-dependent relaxation to A-23187 is probably mediated by NO, but its sensitivity to O2 suggests that two distinct mechanisms may be involved. PMID- 8342646 TI - Fluid shear stress stimulates platelet-derived growth factor expression in endothelial cells. AB - Fluid flow and the associated shear stress play a critical role in vascular growth and remodeling. Recent data suggest that increased endothelial cell expression of platelet-derived growth factor (PDGF) A- and B-chain by flow may participate in these events. In the present study, we examined the mechanism for flow-induced PDGF expression, focusing on protein kinase C (PKC). Bovine aortic endothelial cells were exposed to flow (shear stress = 30 dyn/cm2) in a parallel plate flow chamber. Increases in PDGF B-chain, but not PDGF A-chain, were observed within 3 h, maximal within 6 h (13-fold increase), and sustained for 24 h. PKC appeared to be involved because phorbol 12-myristate 13-acetate induced PDGF B-chain mRNA. Activation of PKC alone, however, was insufficient to induce PDGF mRNA because the selective PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, did not induce PDGF expression. A PKC-independent pathway was suggested by the fact that inhibition of PKC (downregulation with phorbol 12,13-dibutyrate or exposure to staurosporine) failed to block PMA or flow-induced PDGF B-chain expression. These results demonstrate flow-induced PDGF B-chain expression in endothelial cells that appears to be mediated, in part, by a PKC-independent pathway. PMID- 8342647 TI - Effect of adenosine on heart rate in isolated muskrat and guinea pig hearts. AB - The purpose of this study was to compare the responses of isolated hearts of the diving muskrat with the nondividing guinea pig (GP) to determine the contribution of adenosine (ADO) to the profound bradycardia that was seen in isolated muskrat hearts during exposure to hypoxia. Muskrat hearts were more sensitive than GP hearts to the heart rate-lowering effects of exogenously applied ADO or a stable ADO analogue, (R)-N6-(phenylisopropyl)adenosine. The hearts of both species were unpaced, and the bradycardia appeared to be due to high degree of atrioventricular block. Radioligand binding with 8-cyclopentyl-1,3 [3H]dipropylxanthine to A1-ADO receptors was greater in cardiac membranes prepared from GP hearts than from muskrat hearts. Nucleoside transporter antagonist binding was also greater in GP hearts compared with muskrats. This was determined by membrane binding of [3H]-nitrobenzylthioinosine, an antagonist of nucleoside transport. Both muskrat and GP hearts responded to 30 min of hypoxic perfusion by releasing ADO into the coronary effluent; however, the muskrat hearts released approximately five times more than the GP hearts. When hearts were subjected to hypoxia in the presence of ADO deaminase, theophylline, or 8-(p sulfophenyl)theophylline, the hypoxia-induced bradycardia was blocked in the GP hearts and either slightly reduced or not affected in muskrat hearts. In contrast to GP hearts, muskrat hearts release larger amounts of ADO during hypoxia and are more sensitive to the negative chronotropic effects of exogenously administered ADO; yet the hypoxia-induced bradycardia does not appear to be exclusively mediated by ADO in the muskrat as it is in the isolated GP heart. PMID- 8342648 TI - Dependence of cardiac filling pressure on cardiac output during rest and dynamic exercise in dogs. AB - At rest, central venous pressure (CVP) falls when cardiac output (CO) rises. This can be attributed to flow-dependent redistribution of blood volume from central to peripheral blood vessels. In contrast, CVP rises during dynamic exercise despite a rise in CO. Therefore peripheral circulatory changes during exercise must counteract the factors that lower CVP when CO rises during rest. Our objectives were to determine the importance of blood flow, the muscle pump, and reflexes on changes in ventricular filling pressure during dynamic exercise. In seven dogs with a surgically produced atrioventricular (AV) block, normal relationships between CO and CVP were established by AV-linked pacing (normal heart rates) during rest and exercise. Cardiac output was altered during rest and treadmill exercise (4 miles/h at 0, 10, or 20% grade) by changing ventricular pacing rate to establish curves relating delta CVP to delta CO. These curves were displaced rightward (higher CO) and upward (higher CVP) by exercise because of the muscle pump. Changing CO by pacing during rest and exercise revealed a constant slope for delta CVP/delta CO of -2.7 mmHg.l-1.min-1. Blockade of reflex vasoconstriction and venoconstriction with hexamethonium at rest and during mild exercise (to isolate effects of the muscle pump) did not alter these slopes or the displacement of the curves by exercise, although CVP was 4.3 mmHg lower at a given CO after blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342649 TI - Sodium hyperosmolarity of intestinal lymph causes arteriolar vasodilation in part mediated by EDRF. AB - This study evaluated 1) the effect of increased submucosal lymph osmolarity on the regulation of first-order (1A) and second-order (2A) intestinal arterioles and 2) the role of endothelium-derived relaxing factor (EDRF) in hypertonic induced vasodilation. Increasing the submucosal lymph osmolarity from 280 to 400 mosM, in increments of 30 mosM, resulted in a dose-dependent dilation of 1A and 2A. A submucosal lymph tonicity of 340 mosM, as occurs during glucose and oleic acid absorption, caused dilation of 1A (118%) and 2A (124%) equivalent to that during absorptive hyperemia. The dilation caused by 400 mosM mannitol (137%) was similar to that with 340 mosM NaCl (131%) and approximately 70% of that with 400 mosM NaCl (152%). After EDRF blockade, the responses to sodium hypertonicity decreased by about one-half; blockade reduced mannitol-induced dilation by 22%. These results indicate that sodium hypertonicity, as occurs during absorption, can play a major role in absorptive hyperemia, and about one-half of the dilation is related to a sodium-coupled release of EDRF. PMID- 8342650 TI - Catecholamines modulate protein turnover in cultured, quiescent rabbit cardiac myocytes. AB - When rabbit ventricular myocytes were cultured for 1 wk and then exposed to alpha and/or beta-adrenergic agonists, such nonbeating heart cell preparations disclosed increased protein-to-DNA ratios and elevated RNA content, indicative of cellular hypertrophy. Norepinephrine, isoproterenol, and phenylephrine provoked hypertrophy with norepinephrine eliciting a greater response than isoproterenol or phenylephrine. Specific alpha- and beta-antagonists blocked growth by inhibiting catecholamine-induced changes in protein turnover. Each catecholamine enhanced the fractional rate of protein synthesis within 48 h; however, changes in growth rates appeared to be modulated, in part, by alterations in protein degradation. Even though rates of total protein and actin synthesis resembled values measured in vivo, myosin heavy chain fractional rate of synthesis was only 22% of in vivo levels. Double label immunofluorescence microscopy further illustrated that catecholamine treatment accelerated myofibrillar disruption in these quiescent heart cells. These observations suggested that in the absence of beating, neurohumoral modulation of contractile protein turnover was not associated with the maintenance of myofibrillar integrity even though catecholamines induced cellular hypertrophy. PMID- 8342651 TI - Limit to cardiac compensation during acute isovolemic hemodilution: influence of coronary stenosis. AB - We assessed limit to cardiac compensation during isovolemic hemodilution (HD) in 14 anesthetized dogs. Radioactive microspheres were used to evaluate myocardial blood flow (MBF) and its transmural distribution (endo/epi). Myocardial O2 consumption (MVO2) and percent lactate extraction were determined. Coronary vasodilator reserve was assessed from reactive hyperemic responses. Dogs were divided into group 1, with intact left anterior descending coronary artery (LAD), and group 2, with critical stenosis of LAD. Measurements were obtained at baseline and during graded HD (Hespan) until cardiac failure (CF). CF occurred at lower hematocrit in group 1 compared with group 2 (9 +/- 1 vs. 17 +/- 1%). In group 1, MBF increased during HD to maintain MVO2 constant; increases in MBF were transmurally uniform until CF, when decreased endo/epi and lactate production suggested subendocardial ischemia. Coronary vasodilator reserve decreased progressively during HD and was absent at CF. In group 2, stenotic LAD demonstrated constant MBF (resulting in decreased MVO2) during HD. At CF, these responses along with reduced endo/epi and lactate production indicated local myocardial ischemia. We conclude that 1) with normal coronary circulation, cardiac function was well maintained over a wide range of hematocrits because increases in MBF were transmurally uniform and sufficient to maintain myocardial oxygenation: CF occurred during extreme HD when MBF became maldistributed, resulting in subendocardial ischemia; 2) critical coronary stenosis impaired coronary vascular adjustment to HD and reduced significantly tolerance of left ventricle to HD; and 3) present findings underscore the importance of recruitment of coronary vasodilator reserve in preserving total and regional myocardial oxygenation during HD. PMID- 8342653 TI - Coronary arterial tree remodeling in right ventricular hypertrophy. AB - We investigated coronary vascular adaptations occurring in right ventricular hypertrophy (RVH). Six pigs had RVH induced by pulmonary artery stenosis for 5 wk. Three pigs served as controls. At autopsy we made silicone elastomer casts of the right coronary arteries (RCA) and collected morphometric data. We organized the segments and their diameters and lengths into a framework of a modified Strahler's ordering scheme in which the order number of an offspring is increased only if its diameter is greater than the diameters of its parents by a specific amount. The segments of the same order arranged in series are combined into elements. In RVH the total number of orders of vessels was larger than the control by 1; the total number of elements in each order increased greatly, whereas the diameters and lengths of each order decreased somewhat. The total RCA resistance decreased in RVH mainly because the total cross-sectional area (CSA) of every order was increased. Because the diameters of the resistance vessels decreased, this decrease in total RCA resistance was due to a numerical increase in resistance vessels. These findings indicate that new flow channels have been established. In contrast, the RCA was remodeled in that the lumen diameter increased. Pressure-flow curves showed a decrease of coronary resistance in RVH, in agreement with the morphometric findings. We conclude that there is significant remodeling of the coronary arterial vasculature in RVH, and any future analysis of coronary hemodynamics of the right ventricle in hypertrophy must take the morphometric remodeling into account. PMID- 8342652 TI - Morphometry of pig coronary arterial trees. AB - To establish a mathematical model of the tree like arteries for the purpose of hemodynamic analysis, a complete set of morphometric data of pig coronary arteries is presented. For the purpose of mathematical modeling, three innovations in morphometry are introduced: 1) a rule for assigning the order numbers of the vessels on the basis of diameter ranges, 2) a connectivity matrix to describe asymmetric branching, and 3) a measurement of the fraction of vessel segments connected in series. The morphometric measurements were made with the silicone elastomer-casting method. Data on smaller vessels were obtained from histological specimens by optical sectioning. Data on larger vessels were obtained from vascular casts. The order number, diameter, length, connectivity matrix, and fractions of the vessels of a given order connected in series were measured for all orders of vessels of the right coronary artery and the left anterior descending and left circumflex branches. The data can be used to analyze the longitudinal distribution of blood pressure and volume and spatial distribution of perfusion in myocardium. PMID- 8342654 TI - Increasing oxygen tension dilates fetal pulmonary circulation via endothelium derived relaxing factor. AB - We examined the role of endothelium-derived relaxing factor (EDRF) in the increase in pulmonary blood flow caused by increasing oxygen tension in the lungs of the fetus. Fetal lambs at 133 days of gestation were instrumented for intrauterine measurement of pulmonary arterial, left atrial, and amniotic fluid pressure and pulmonary blood flow. Three days later oxygen tension in the pulmonary arterial blood of the fetus was doubled by having the ewe breathe 100% oxygen at 3 atm absolute pressure. In the control fetuses (n = 5), hyperbaric oxygenation increased pulmonary blood flow eightfold. Blocking EDRF production by infusing 45 mg of NG-monomethyl-L-arginine into the superior vena cava of the fetus over 5 min starting 30 min after the beginning of hyperbaric oxygen reversed the increase in pulmonary blood flow (n = 5). Blocking EDRF production by infusing NG-nitro-L-arginine at 1 mg/min for 60 min starting 30 min before hyperbaric oxygen blunted the initial increase in pulmonary blood flow and eliminated it by the end of the experiment (n = 5). As hyperbaric oxygen did not significantly alter pulmonary arterial or left atrial pressure, changes in pulmonary vascular conductance paralleled those in pulmonary blood flow. We conclude that the majority of the vasodilation of the fetal pulmonary circulation caused by increasing oxygen tension is mediated by EDRF. We speculate that EDRF is involved in maintaining low vascular tone at the relatively high oxygen tension of the postnatal lung. PMID- 8342655 TI - Pressure-related capillary leukostasis following ischemia-reperfusion and hemorrhagic shock. AB - Although the receptor-dependent venular adhesion of leukocyte adherence has been relatively well characterized, less is known about capillary leukostasis. With the use of fluorescence intravital microscopy, leukocyte behavior in the capillaries of rabbit tenuissimus muscle was evaluated after ischemia-reperfusion or hemorrhage. After fixed volume hemorrhage or 4 h of total ischemia, inflammatory injury was manifest by broken fibrils, edema, leukocyte infiltration, and margination along the postcapillary venular walls. Nevertheless, as long as arterial perfusion pressure was between 27 and 72 mmHg, the frequency of capillary leukostasis was low (4-8 cells/mm2) and similar in all groups, including animals treated with the antiadhesion antibody IB4. In contrast, when perfusion pressure decreased to 20 mmHg, capillary leukostasis increased similarly (to 16-21 cells/mm2) in controls (with or without IB4) and in those subjected to ischemia. Furthermore, when perfusion pressure was increased to more than 27 mmHg, (27-72 mmHg) stationary leukocytes returned to the original low level (4-5 cells/mm2). These results are consistent with the conclusion that during some inflammatory injuries, capillary leukostasis is a pressure-related phenomena that is not receptor dependent and is freely reversible with the early restoration of perfusion pressure. PMID- 8342656 TI - Altered cerebrovascular responsiveness to N-methyl-D-aspartate after asphyxia in piglets. AB - We examined effects of prior asphyxia and reventilation on pial arteriolar responses to arterial hypercapnia, topical application of forskolin, and topical application of N-methyl-D-aspartate (NMDA) in newborn pigs. Piglets were anesthetized and ventilated with a respirator. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. After baseline diameter was determined, the respirator was turned off for 10 min. Then the respirator was turned on, and the piglet was ventilated for 4 h. At 1, 2, and 4 h after asphyxia, arteriolar diameter was determined during control conditions and during arterial hypercapnia (inspiration of 10% CO2 in air; n = 4), topical application of 2.4 x 10(-8) M forskolin (n = 6), and topical application of 10( 5) M NMDA (n = 6). At 1 h after asphyxia, arterial hypercapnia dilated pial arterioles by 39 +/- 3%, topical forskolin dilated pial arterioles by 24 +/- 3%, and NMDA dilated pial arterioles by 10 +/- 1%. For arterial hypercapnia and forskolin application, arteriolar responses were not different from 1 h at 2 and 4 h postasphyxia. In contrast, for NMDA, arteriolar responses were greater at 2 h (23 +/- 6%) and 4 h (30 +/- 5%) than at 1 h. In time-control animals, NMDA dilated arterioles by 20 +/- 5% at 1 h, by 24 +/- 8% at 2 h, and by 21 +/- 4% at 4 h (n = 5). Indomethacin administration (5 mg/kg iv) before asphyxia resulted in a 23 +/- 3% arteriolar dilation in response to NMDA at 1 h (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342657 TI - Age-dependent overflow of endogenous norepinephrine from paraventricular hypothalamic nucleus of hypertensive rats. AB - The relationship between age and central noradrenergic neuronal activity of the paraventricular hypothalamic nucleus (PVH) was examined in 7- to 10-, 12- to 14-, and 30- to 36-wk-old Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR). As an index of noradrenergic activity, endogenous norepinephrine (NE) overflow was assessed utilizing a miniaturized push-pull cannula assembly in unanesthetized freely moving rats. NE overlow under basal, 56 mM K+ stimulation, and in response to pressor/depressor drugs, were examined in all three strains at all ages. Significant increases in basal and K(+)-stimulated overflow of endogenous NE from the PVH were observed in all ages of SHR compared with normotensive controls with the greatest percent increase occurring during the development of hypertension in SHR. In addition, a reciprocal relationship exists with respect to blood pressure and overflow of NE from the PVH such that increases/decreases in blood pressure elicit decreases/increases in NE overflow in all strains at all ages examined. However, developing hypertensive SHR exhibited attenuated decreases in overflow of NE from the PVH compared with age matched controls and established hypertensive SHR. These results suggest that noradrenergic pathways of the PVH contribute to the development and maintenance of arterial pressure hemostasis and that enhanced central noradrenergic neuronal activity is greatest during the development of hypertension in SHR. PMID- 8342658 TI - Activation of cardiac sympathetic afferents: effects of exogenous adenosine and adenosine analogues. AB - Adenosine is released during myocardial ischemia and can cause angina-like chest pain when given by intracoronary administration. We tested the hypothesis that intracoronary adenosine activates cardiac sympathetic afferent fibers and results in reflex sympathoexcitation. In dogs with sinoaortic denervation and vagotomy, we administered 2 mg of adenosine into the left anterior descending artery over 2 min. Before dipyridamole infusion, intracoronary adenosine resulted in no change in blood pressure or renal sympathetic nerve activity. After dipyridamole infusion, which blocks adenosine uptake, intracoronary adenosine resulted in a peak increase in sympathetic activity of 34 +/- 7%. We also investigated the adenosine-receptor subtype responsible for this sympathoexcitatory response. We found that the adenosine1 agonist N6-cyclopentyladenosine elicited a dose dependent sympathoexcitatory response similar to adenosine but that the adenosine2 agonist 5'-(N-cyclopropyl)carboxamidoadenosine failed to elicit a sympathoexcitatory response. We conclude that adenosine activates cardiac sympathetic afferent fibers and leads to a sympathoexcitatory response due to activation of adenosine1 receptors. PMID- 8342659 TI - Biologic role of atrial natriuretic factor clearance receptor in congestive heart failure. AB - Atrial natriuretic factor (ANF) is a circulating 28-amino acid peptide that functions in the regulation of sodium homeostasis and vascular tone. ANF metabolism occurs via degradation by neutral endopeptidase 24.11 and binding to the ANF clearance receptor (ANFR-C). The present study was performed on anesthetized dogs, normal (control) and with experimental congestive heart failure (CHF), and was designed to investigate the ability of an ANF ligand specific for ANFR-C [C-ANF-(4-23)] to increase plasma ANF and also to evaluate the influence of ANFR-C on regional pulmonary and renal ANF clearances. C-ANF-(4 23) increased plasma ANF in controls (51 +/- 15 to 123 +/- 39 pg/ml; P < 0.05) and further increased plasma ANF in CHF dogs (242 +/- 30 to 327 +/- 34; P < 0.05), demonstrating that ANFR-C plays a significant role in the overall metabolism and clearance of ANF, even with chronically elevated ANF. Infusion of C-ANF-(4-23) produced a marked decrease in ANF pulmonary clearance (PCLANF) in controls (1,018 +/- 405 to -286 +/- 383 ml/min; P < 0.05); however, PCLANF was not altered by the ANF ligand in CHF dogs [-137 +/- 174 to -106 +/- 226 ml/min; not significant (NS)], suggesting an occupancy of ANFR-C or a downregulation of this receptor with chronically elevated plasma ANF. ANF renal clearance (RCLANF) was not altered in either group by C-ANF-(4-23) infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342660 TI - Role of nitric oxide in leukotriene C4-induced increases in microvascular transport. AB - The goal of this study was to determine the role of nitric oxide in alterations in macromolecular transport of the hamster cheek pouch in vivo in response to leukotriene C4. We used intravital fluorescent microscopy to examine the transport of macromolecules across the hamster cheek pouch in response to leukotriene C4 before and after application of an enzymatic inhibitor of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 1.0 microM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC dextran; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increase in the number of venular leaky sites and clearance of FITC-dextran-70K. Superfusion of L-NMMA (1.0 microM) significantly decreased leukotriene C4-induced increases in venular leaky sites and clearance of FITC-dextran-70K. In addition, superfusion of LY-83583 (10 microM) significantly decreased leukotriene C4 induced increases in venular leaky sites. In contrast, superfusion of NG monomethyl-D-arginine (D-NMMA; 1.0 microM), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-20 mg/kg iv) did not significantly alter leukotriene C4-induced increases in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play an important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4. PMID- 8342661 TI - Myogenic tone is coupled to phospholipase C and G protein activation in small cerebral arteries. AB - The cellular transduction mechanisms underlying the response of blood vessels to mechanical forces such as pressure or stretch are largely unknown. In this report we test the hypothesis that myogenic tone in the cerebral circulation is coupled to activation of phospholipase C (PLC) and G proteins. Rat posterior cerebral arteries (luminal diam 189 +/- 4 microns) were cannulated in an arteriograph and allowed to develop myogenic tone at 75 mmHg (122 +/- 6 microns; P < 0.01). Exposure to U-73122, an inhibitor of PLC, produced concentration-dependent vasodilation, with near-maximal (> 90%) inhibition at concentrations > 3 microM (50% inhibitory concentration = 0.8 +/- 0.04 microM). The action of U-73122 was confirmed by demonstrating that constrictor responses to serotonin (PLC mediated) could be significantly attenuated or abolished at concentrations (0.5-1 microM) that were ineffective in antagonizing potassium depolarization or indolactam induced constrictions (both PLC independent). Incubation in pertussis toxin (100 ng/ml, 2-2.5 h), an inhibitor of some G protein subtypes, reduced myogenic tone by 74 +/- 12%, with luminal diameters increasing from 129 +/- 7 to 160 +/- 7 microns. Conversely, nonspecific G protein activation using AlF-4 (NaF+AlCl3, 0.5 5 mM) significantly increased myogenic tone by 86 +/- 9%, reducing luminal diameters from 132 +/- 6 to 88 +/- 8 microns (P < 0.01). Together, these findings suggest that 1) PLC is activated in arteries that possess myogenic tone, 2) pharmacological inhibition of PLC results in a virtual loss of pressure-induced constriction, and 3) G proteins may modulate mechanotransduction through pathways superimposed on basal myogenic tone. PMID- 8342662 TI - Dietary sodium stimulates ouabainlike activity in adrenalectomized spontaneously hypertensive rats. AB - Both the adrenal glands and the hypothalamus have been proposed to produce compound(s) with ouabainlike activity (OLA). To evaluate the contribution of the adrenal glands, 4-wk-old spontaneously hypertensive rats (SHR) were sham operated or adrenalectomized. The adrenalectomized SHR were given daily injections of corticosterone and aldosterone. Subsequently, rats were randomized to control or high (8%) dietary Na+, and after 2.5 wk, blood pressure and OLA in plasma, hypothalamus, and pituitary were evaluated. Hypertension developed somewhat less in adrenalectomized vs. sham-operated SHR. On control Na+ intake, adrenalectomy caused only minor decreases in circulating and central OLA. Adrenalectomy did not prevent the 50-90% increases in plasma, hypothalamus, and pituitary OLA caused by high Na+ intake for 2.5 wk. These findings are consistent with the concept that, at least in SHR, the central nervous system may represent the major source of both central and peripheral OLA. PMID- 8342663 TI - Microvascular volume shift and fluid restitution induced by lower-body suction. PMID- 8342664 TI - Neutral axis location in bending and Young's modulus of different layers of arterial wall. AB - With few exceptions, experimental results on the blood vessel elasticity have been analyzed with the blood vessel wall treated as a homogeneous material, probably because the experiments have been limited to inflation and stretching. To advance the subject, we must evaluate the force-deformation relationship of different layers of the vessel. A key strategy to do this is to study nonaxisymmetric deformation of the vessel wall so that the different layers of the vessel may deform in different amounts at different places. One of the most effective nonaxisymmetric deformations that can be imposed on the vessel wall is bending. The first important question to ask about bending is, Where is the neutral axis? In this study, a method to determine the neutral axis is presented. We found that the neutral axis of the aorta of the pig lies in the medial layer about one-third of the wall thickness from the endothelium. We measured the strain distribution in the vessel wall by optical methods. Using the load deflection relationship, we evaluated the Young's modulus of the intima-media layer and that of the adventitia. They differ by an order of magnitude. Our results show that the Young's modulus of the intima-media layer of the pig thoracic aorta is 43.2 +/- 15.8 kPa, whereas the Young's modulus of the adventitial layer is 4.70 +/- 1.72 kPa, in a linear range of the stress-strain relationship including the zero-stress state and the no-load state. PMID- 8342665 TI - Myocardial capillary diffusion capacity in rat hearts with cardiac hypertrophy due to pressure and volume overload. AB - The functional adaptation of the myocardial capillary bed in response to cardiac hypertrophy was studied in one volume overload (aortocaval fistula, ACF) and in one pressure overload model [left renal arterial stenosis, two-kidney, one-clip (2K,1C)]. Furthermore, a group where renal hypertension was reversed 1 wk before experimentation (UC-2K,1C) and a sham-operated (Sham) group were studied. Functional estimations of myocardial capillary diffusion capacity in terms of permeability surface area products (PS) per 100 g of myocardium were obtained by the single-injection indicator dilution technique in a Langendorff preparation. After 4 wk, ACF hearts, with 72% hypertrophy and normal minimal coronary vascular resistance (CVR), displayed an unchanged diffusion capacity, i.e., PS for Cr-EDTA and vitamin B12. This indicates a structural out-growth of the coronary vascular bed to match the increased demand of the tissue. 2K,1C hearts with marked elevations of minimal coronary vascular resistance and left ventricular hypertrophy (65%) showed higher PS values than Sham, implying that diffusion capacity was enhanced despite structural coronary vascular changes. These changes were completely reversed in UC-2K,1C. Thus the present data imply that myocardial capillary diffusion capacity was well maintained in volume overloaded cardiac hypertrophy and in contrast with earlier morphometric estimations, even enhanced in pressure overload hypertrophy. PMID- 8342666 TI - Hemodynamic responses to graded lower body positive pressure. AB - Fourteen healthy young men were exposed to progressive increases in lower body positive pressure (LBPP) from 0 to 40 Torr in the supine position. Central venous pressure (CVP) increased 1.09 mmHg (P < 0.05) at 5 Torr LBPP. Between 20 and 40 Torr LBPP CVP increased 0.85 mmHg, resulting in a total increase of 2.06 mmHg (P < 0.05). During 0-20 Torr LBPP mean arterial pressure (MAP) increased from 86 to 89 mmHg with a slope of 0.15 mmHg/Torr LBPP. Stroke volume and cardiac output were significantly increased at 20 Torr LBPP. Beyond 20 Torr LBPP, MAP increased to 95 mmHg at 40 Torr (P < 0.05) with a slope of 0.32 mmHg/Torr LBPP. Forearm blood flow increased above rest at 40 Torr LBPP (P < 0.05). However, neither peripheral nor forearm vascular resistance decreased significantly from rest. Despite the significant increases in MAP, heart rate was unchanged above 20 Torr LBPP. These data suggest that LBPP produces increases in CVP at 0-20 Torr by translocation of blood volume from the legs to the thorax. At LBPP > 20 Torr, further increases in CVP and MAP were produced by other mechanisms possibly related to an activation of intramuscular pressure-sensitive receptors. PMID- 8342667 TI - Albumin modulation of capillary permeability: role of endothelial cell [Ca2+]i. AB - Albumin is required in vascular perfusates to maintain the normal permeability of microvessel walls. The most common mechanism proposed for action of albumin involves binding to the endothelial cell surface to increase the resistance to water and solute flows through hydraulic pathways across the capillary wall. The results of the present experiments do not conform to this simple adsorption model. Ringer perfusion increased the hydraulic conductivity (Lp) of the wall of single perfused frog mesenteric microvessels by 4.0 +/- 0.5-fold. The increase in Lp was associated with an increase of cytoplasmic calcium concentration ([Ca2+]i) from 59 +/- 5 nM when albumin was in the perfusate to a transient peak of 181 +/- 13 nM, 1-2 min after Ringer perfusion. [Ca2+]i then fell back to close to 100 nM. Processes that reduced Ca2+ influx into endothelial cells (removal of extracellular Ca2+, membrane depolarization) reduced Ca2+ influx and attenuated the increase in [Ca2+]i. The same processes abolished the increase in Lp after Ringer perfusion and restored Lp to close to control values during Ringer perfusion. Thus Ca2+ entry into endothelial cells is required to initiate and maintain the increased permeability during Ringer perfusion. PMID- 8342668 TI - Magnesium influences incorporation of [3H]arachidonic acid in perfused rabbits hearts. AB - Ca(2+)-free perfusion of rabbit hearts produces a 50% loss of tissue Ca2+ and Mg2+ and results in reduced incorporation of arachidonic acid into tissue lipids. This work was undertaken to determine whether the reduced incorporation was specific for arachidonic acid and whether it was correlated to the loss of either (or both) cation(s). Single 170-pmol bolus doses of [3H]arachidonic or [3H]oleic acid were given to perfused hearts with or without Ca2+ in the perfusate. The experiment was terminated, and the lipids were extracted 1-15 min after administration of label. At all time points, significantly less arachidonate was incorporated into total tissue lipids in the absence of than in the presence of Ca2+. The presence or absence of Ca2+ had no effect on the incorporation of oleate. When [3H]arachidonate was administered to hearts perfused with buffer containing 104 mM Li+ and 35 mM Na+ (which reduces tissue Mg2+ by approximately 25% and increases tissue Ca2+ by approximately 35%), the incorporation into lipids was reduced from 0.882 +/- 0.0739 to 0.598 +/- 0.0722 pmol/mg lipid (P < 0.05; n = 6). The incorporation of [3H]oleate during 104 mM Li+ and 35 mM Na+ was not different from control. These data suggest that the incorporation of arachidonic, but not oleic, acid into tissue lipids is dependent on the tissue Mg2+ content. PMID- 8342669 TI - Fetal responses to acute maternal cocaine injection in sheep. AB - Maternal cocaine abuse has been associated with neonatal neurological and neurobehavioral problems of unknown pathogenesis. We administered a single intravenous dose of cocaine (2 mg/kg) to 12 unanesthetized pregnant sheep; their fetuses had been catheterized in utero 2 days before the study. We measured fetal cerebral blood flow (CBF), cerebral metabolic rate of O2 (CMRO2), mean arterial blood pressure (MAP), and blood gases before and 2, 5, 15, and 30 min after maternal cocaine injection. Fetal CBF increased by 37 +/- 33% (mean +/- SD) at 5 min and returned to baseline by 15 min. Regional brain blood flow changes paralleled CBF changes with the greatest increases occurring in cerebellum (54 +/ 43%) and brain stem (54 +/- 52%). Cerebral vascular resistance was decreased for cerebellum (22%) and brain stem (19%) but was unchanged for cerebral hemispheres and caudate. Increased CBF at 5 min was associated with a 20 +/- 9% increase in fetal MAP and a 38 +/- 13% decrease in fetal arterial O2 content. Fetal CMRO2 was unchanged. There was a decrease in fetal intestinal blood flow at 2 min, an increase in myocardial, adrenal, and renal blood flow at 5 min, and no change in placental blood flow. Maternal cocaine injection causes fetal hypoxemia, hypertension, and increased CBF. Possible mechanisms for cerebral vasodilation (in some areas) include hypoxemia, impaired autoregulatory response to increased blood pressure, and/or direct or indirect vascular effects of cocaine or its metabolites. PMID- 8342670 TI - VIP and NPY in canine hearts. Distribution and effect of total and selective parasympathetic denervation. AB - The hypotheses that vasoactive intestinal peptide (VIP) is evenly distributed throughout atrial and ventricular myocardium and is present in postganglionic parasympathetic neurons in the regions of the sinoatrial and atrioventricular nodes were tested in three groups of dogs. Neuropeptide Y (NPY) tissue concentrations were determined in each group. In six sham dogs VIP and NPY concentrations were evenly distributed and were higher in atria compared with ventricles. In nine parasympathectomized dogs, VIP concentrations in sample sites from regions of the sinoatrial and atrioventricular nodes were comparable to those in sham-operated controls. In nine denervated dogs VIP concentrations were significantly decreased in three adjacent sample sites along the atrioventricular groove. In these dogs NPY concentrations were not detectable or were significantly decreased at all sample sites of both atria and ventricles. These data suggest that VIP neurons are evenly distributed in atrial and ventricular myocardium but do not originate in parasympathetic ganglia supplying the sinoatrial and atrioventricular nodes. The data also demonstrate the possible presence of extrinsic VIP neurons in the canine right ventricle and indicate that NPY may be a useful marker of myocardial adrenergic innervation. PMID- 8342671 TI - Baroreflex control of arterial and venous compliances and vascular capacity in hypertensive dogs. AB - The ability of the carotid sinus baroreflex to elicit reflex changes in vascular capacity was studied in chronically hypertensive (one-kidney, one-clip) and sham operated normotensive dogs under pentobarbital sodium anesthesia. Vascular compliances and reflex-induced changes in external reservoir volume were measured in response to changes in isolated carotid sinus pressure (CSP). The mean arterial pressure-CSP reflex characteristic curve was shifted to a higher arterial pressure with hypertension with no change in maximum reflex gains. Arterial compliance in both groups increased significantly (P < 0.01) when CSP was increased from 50 to 200 mmHg. Total, arterial, and venous vascular compliances were not different in normotensive and hypertensive groups. Changes in CSP caused no significant changes in either total systemic vascular or calculated venous compliances. A decrease in CSP from 250 to 50 mmHg resulted in an increase in external reservoir volume of 8.02 +/- 1.03 and 7.44 +/- 1.33 ml/kg in normotensive and hypertensive groups, respectively, with changes in venous volume of 11.99 +/- 1.39 and 12.58 +/- 1.52 ml/kg (NS). We conclude that despite the increase in arterial resistance, Goldblatt hypertensive dogs retain the ability to make short-term reflex adjustments in both arterial pressure and venous blood volume. PMID- 8342672 TI - Adrenal medulla as a mediator of diet-induced hypertension. AB - Male Sprague-Dawley rats fed either a high-fat or glucose-enriched diet for 10 wk developed higher blood pressure (BP) and higher urinary catecholamine excretion than rats fed a control diet. After 10 wk of diet treatment, systolic BP was 164 +/- 3, 156 +/- 2, and 145 +/- 4 mmHg in rats fed the high-fat, glucose, and control diets, respectively (P < 0.02 vs. control). During weeks 7-9 of diet treatment, excretion of epinephrine and norepinephrine was increased in hypertensive rats (those fed the high-fat or glucose diet) when compared with rats fed the control diet (P < 0.001). The purpose of this study was to determine whether the hypertensive response to nutrients could be prevented by prior surgical removal of the adrenal medulla. Adrenal demedullation nearly abolished epinephrine excretion, attenuated norepinephrine excretion, and completely blocked the hypertensive response to dietary fat and glucose. These findings suggest that adrenal medullary catecholamines play a role in the hypertensive response to nutrients. PMID- 8342673 TI - Norepinephrine does not stimulate protein and UCP synthesis in brown adipocytes of golden Syrian hamsters. AB - Hamster brown adipocytes were incubated for up to 24 h with or without norepinephrine (NE) in Dulbecco's modified Eagle's medium supplemented with bovine serum albumin, calf serum, and antibiotics. Brown fat cells were viable for 24 h as defined by their ability to respond to NE by a 10-fold increase in oxygen consumption. However, prolonged exposure of the cells to NE led to a decline in NE-stimulated rates of O2 consumption, which was not the result of loss of cell thermogenic capacity. Brown fat cells incubated for 24 h with or without NE showed no significant change in succinate dehydrogenase activity or uncoupling protein (UCP) content. However, cell recovery after 24 h was significantly reduced in the absence of NE. In brown adipocytes isolated from rat, NE increased [35S]methionine incorporation into cell proteins and UCP. In contrast, [35S]methionine incorporation in hamster brown adipocyte proteins and UCP was greater than in rat brown fat cells and was not increased by NE. These results indicate that although NE may be required for cell survival, it does not stimulate protein and UCP synthesis in hamster brown fat cells. PMID- 8342674 TI - Supramedullary inputs to cardiovascular neurons of rostral ventrolateral medulla in rats. AB - Experiments were done to test the hypothesis that selective activation of cell bodies in different nuclei known to be involved in central cardiovascular control could excite or inhibit the discharge of neurons in the rostral ventrolateral medulla (RVLM). It is known that chemical stimulation of the lateral parabrachial nucleus (LPBN), locus ceruleus (LC), and lateral hypothalamic area (LHA) in anesthetized animals elicits increases (LPBN) or decreases (LC and LHA) in arterial pressure. We therefore recorded extracellularly spontaneous activity from RVLM units in urethan-anesthetized rats and monitored the changes in firing frequency of these neurons during chemical stimulation of one of LPBN, LC, and LHA. Thirty-two units were classified as cardiovascular neurons because their activity was inhibited by baroreceptor activation (1-3 micrograms phenylephrine iv) and displayed a cardiac cycle-related rhythmicity. Chemical stimulation with sodium glutamate of arterial pressor sites in the ipsilateral LPBN increased the firing frequency (40.3 +/- 1.3%) of 11 cardiovascular neurons. Activation of cell bodies in arterial depressor sites in the ipsilateral LC inhibited the firing rate (59.1 +/- 7.1%) of 10 cardiovascular neurons and excited 1 unit. Activation of cell bodies in arterial depressor sites in the ipsilateral LHA inhibited the discharge rate (25.4 +/- 4.7%) of six cardiovascular neurons, excited one unit, and did not alter the rate of the remaining three units. These results provide direct evidence for the existence of excitatory and inhibitory pathways from neurons located in the LPBN, LC, and LHA to cardiovascular neurons in the RVLM. PMID- 8342675 TI - Responses to catecholamines in perfused livers of hypothalamic-lesioned rats. AB - The responses of hepatic glycogenolysis to catecholamines in ventromedial hypothalamus (VMH)-lesioned male rats were examined in perfused livers. Seven days after bilateral electrical lesioning of the VMH, the livers were perfused. Isoproterenol, a beta-agonist, stimulated greater glucose production in VMH lesioned rats than in controls (32.8 vs. 5.6 mumol glucose.h-1.g liver-1), while responses to phenylephrine, an alpha-agonist, decreased significantly compared with controls (44.4 vs. 69.8 mumol glucose.h-1.g liver-1). There were no significant differences in responses of livers to glucagon and vasopressin between control and VMH-lesioned rats. Adrenodemedullation showed the same effect on beta-responses as lesions in the VMH, but no effect on alpha-responses. Plasma epinephrine levels were not detectable with the high-performance liquid chromatography analysis in VMH-lesioned rats. The periodicity of plasma corticosterone levels was observed in both VMH-lesioned and control rats, although daytime increases in plasma corticosterone were blocked by VMH lesions. These results suggest that the lesions in the VMH cause changes in the levels of adrenergic receptor and that the increase in beta-responses is caused mostly by the reduction of plasma epinephrine. PMID- 8342676 TI - Single-pass gill extraction and tissue distribution of atrial natriuretic peptide in trout. AB - A new method is described in the present experiments to quantify atrial natriuretic peptide (125I-ANP) extraction from plasma in a single transit through the gill vasculature of an unanesthetized trout. Tissue distribution of 125I relative to an inert extracellular space marker, 58Co-EDTA, was also measured 1 h after injection of 125I-ANP. Single-pass extraction of 125I-ANP by the gill was 60% in control fish; it fell to 18% in fish previously injected with saline and became negative (relative to 58Co-EDTA) after treatment with the clearance (C type) receptor inhibitor SC 46542. Approximately 90% of a 125I-ANP bolus injected into control trout is removed from the circulation within 2 min. 125I concentration in gill tissue was nearly seven times greater than that predicted by the 58Co-EDTA space. 125I was also concentrated in brain (2X), gallbladder, gastrointestinal tract, and eye (all 1X). SC 46542 decreased gill 125I binding from seven times to one times the 58Co-EDTA space and increased 125I accumulation in heart, kidney, fat, and skeletal muscle. Extraction of 125I-ANP by the isolated perfused gill was 53%, similar to that observed in vivo. These results show that the gill is a major site for ANP removal from trout plasma and that C type receptors are predominant in this process. PMID- 8342677 TI - Effects of capsaicin on micturition and associated reflexes in rats. AB - The effect of capsaicin on micturition and associated reflexes was studied in urethan-anesthetized female rats. Capsaicin or vehicle solution were administered 4 days before the experiment in a dose of 125 mg/kg sc or during the experiment in a dose of 50-100 mg/kg sc. Activity of the urinary bladder was recorded by measuring intravesical pressure via a urethral catheter while slowly filling (0.052 ml/min) the bladder or when the bladder was distended beyond the micturition threshold and maintained at a constant volume. Pretreatment with capsaicin did not significantly change various parameters of urinary bladder function including micturition volume threshold or the amplitude, duration, and interval between reflex bladder contractions. However, capsaicin pretreatment significantly reduced (80% decrease) the arterial pressor responses accompanying reflex bladder contractions and reduced by approximately one-half the percentage of animals in which bladder activity was inhibited by stimulation of the uterine cervix. A large dose of capsaicin (50 mg/kg sc) elicited an acute block of bladder activity that persisted for 8-15 h. This effect is attributable to an action on myelinated afferent or efferent components of the micturition reflex pathway. It is concluded that capsaicin-sensitive afferents are not essential for the performance of micturition in the rat. However, these afferents are involved in cervicovesical reflex mechanisms that modulate bladder activity and in vascular reflexes triggered by isometric bladder contractions. PMID- 8342678 TI - Fate of circulating amino-terminal propeptide of type III procollagen in conscious pigs. AB - The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs with a thoracic duct-venous shunt, 125I-labeled PIIINP was injected intravenously. The initial distribution volume was 2.2 liters, which was 1.7 times the plasma volume (P < 0.01). The disappearance curve was three-phased, with an initial steep decline (t1/2 58 min), followed by two slower phases (t1/2 239 min and 289 h). Consecutive gel filtrations showed that the initial slope of the plasma disappearance curve corresponded to the plasma clearance of the intact PIIINP. The initial plasma clearance was 26.5 ml plasma/min, whereas the urinary clearance was 8.7 ml plasma/min (P < 0.01). The other components of the plasma disappearance curve originated from the formation and disappearance of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M(r) 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive component. The existence of the low MW fraction (approximately M(r) 20,000) has not been reported before. The lymphatic recirculation of intact PIIINP was rapid, and the lymph-serum ratio was almost constant within 1 h of injection. We conclude that the t1/2 of circulating PIIINP is 58 min, that PIIINP escapes the circulation very quickly, and that the degradation of PIIINP includes at least two intermediary steps. PMID- 8342679 TI - Inhibition of chemoreceptor inputs to nucleus of tractus solitarius neurons during baroreceptor stimulation. AB - The reflex effects of arterial chemoreceptor activation are attenuated as arterial pressure is elevated and augmented as arterial pressure is decreased. This study was designed to test the hypothesis that excitatory arterial chemoreceptor inputs to neurons in the nucleus tractus solitarius (NTS) are inhibited by arterial baroreceptors. In pentobarbital sodium-anesthetized, mechanically ventilated, paralyzed cats, extracellular recordings were obtained from NTS neurons, which were excited after brief activation of ipsilateral carotid body chemoreceptors. During increases in arterial pressure, carotid sinus nerve (CSN)-evoked discharge was 45-112% of the control-evoked discharge at the prevailing level of arterial pressure (n = 70). Inhibition of CSN-evoked discharge during increased arterial pressure was significant when evoked discharge was < 90% of control (n = 31; 67 +/- 2%, mean percent of control-evoked discharge +/- SE; P < 0.01, Wilcoxon signed-rank test). The inhibition of CSN evoked discharge was reduced after section of both vagi, both aortic nerves, and the contralateral CSN (n = 5, P < 0.05). These results demonstrate that activation of arterial baroreceptors attenuates excitatory chemoreceptor inputs to a subpopulation of NTS neurons. The inhibition appears to be mediated by disfacilitation. The results indicate that baroreceptor modulation of arterial chemoreflexes occurs at an early stage of the reflex arc, within the NTS. The results also suggest that sympathoinhibition evoked by baroreceptors might include, as a component, reduced sympathoexcitatory, i.e., chemoreceptor, drive. PMID- 8342680 TI - Energy balance and lipid metabolism in transgenic mice bearing an antisense GCR gene construct. AB - Energy balance and lipid metabolism were investigated in transgenic mice bearing an antisense glucocorticoid receptor (GCR) gene construct that impairs the normal expression of the GCR gene. Food intake was recorded during the 15 days preceding decapitation of adult normal and transgenic mice, and feces were collected to derive the digestible energy intake. Body composition measurements consisted of the determination of energy, protein, and fat content of the carcass. Carcass energy was determined by bomb calorimetry, whereas carcass protein was measured by the Kjeldahl procedure. Energy expenditure was estimated from the continuous oxygen consumption (VO2) monitoring over a 24-h period. Lipoprotein lipase (LPL) activity was quantified in epididymal white adipose tissue (WAT), heart, and vastus lateralis muscle (VLM) by measuring the in vitro hydrolysis of labeled triolein in the presence of tissue homogenates. Norepinephrine (NE) content of both interscapular brown adipose tissue (BAT) and heart were determined by high performance liquid chromatography (HPLC). Energy intake and expenditure were significantly lower in transgenic mice than in controls. Concurrently, both fat content and total energy of the carcasses were significantly higher in the transgenic animals. In comparison with normal mice, heart and VLM LPL activity was significantly reduced in transgenic mutants. There was no difference between groups in LPL activity in WAT. Finally, heart and BAT NE contents were lower in transgenic animals than in control mice. These results suggest that a defective GCR system may affect energy balance through increasing energetic efficiency, and they emphasize the modulatory effects of hypothalamic-pituitary-adrenal axis changes on muscle LPL activity. PMID- 8342681 TI - Possible involvement of brain oxytocin in modulating vasopressin antipyretic action. AB - Experiments were undertaken to test whether oxytocin (OT) may modulate the antipyretic action of arginine vasopressin (AVP) and to determine whether the action of endogenously released OT and/or AVP evoked by fever may modulate the motor actions of exogenous AVP. Intracerebroventricular (icv) injection of interleukin-1 alpha (IL-1 alpha, 40 ng) elicited a significantly attenuated rise in body temperature during the 2nd h of the febrile responses in OT-pretreated (0.1-10 pmol icv, 24 h earlier) rats. At the end of the 2nd h, administration of AVP (1 pmol icv), but not OT (10 pmol icv), significantly suppressed the febrile response in OT-pretreated but not in saline-pretreated rats. In nonfebrile OT pretreated rats, 10 but not 1 pmol of AVP (icv) caused a significant decrease in body temperature. In rats pretreated with IL-1 alpha (40 ng icv) injection of AVP (100 pmol icv) induced enhanced motor responses. In summary, the ability of OT pretreatment to alter the febrile response to IL-1 alpha and the antipyretic action of AVP suggests a role for this peptide in fever. Furthermore, the observation that fever pretreatment can lower the threshold for convulsive-like behavior evoked by subsequent exposure to AVP raises the possibility that central OT and/or AVP released during fever could play a role in the genesis of febrile convulsions. PMID- 8342682 TI - Metabolism and energetics in squid (Illex illecebrosus, Loligo pealei) during muscular fatigue and recovery. AB - The concentrations of intermediate and end products of anaerobic energy metabolism and of free amino acids were determined in mantle musculature and blood sampled from cannulated, unrestrained squid (Loligo pealei, Illex illecebrosus) under control conditions, after fatigue from increasing levels of exercise, and during postexercise recovery. Phosphagen depletion, accumulation of octopine (more so in Illex than in Loligo), and accumulation of succinate indicate that anaerobic metabolism contributes to energy production before fatigue. Proline was a substrate of metabolism in Loligo, as indicated by its depletion in the mantle. In both species, there was no evidence of catabolism of ATP beyond AMP. A comparison of the changes in the free and total levels of adenylates and the phosphagen indicates an earlier detrimental effect of fatigue on the energy status in Loligo. The acidosis provoked by octopine formation in Illex was demonstrated to promote the use of the phosphagen and to protect the free energy change of ATP such that the anaerobic scope of metabolism during swimming is extended and expressed more in Illex than in Loligo. In both species, there was no decrease in the sum of phospho-L-arginine, octopine, and L-arginine, and thus no release of octopine from the mantle, thereby supporting our earlier claim that octopine and associated protons are recycled in the mantle tissue. Overall, the metabolic strategy of Loligo is much less disturbing for the acid base status. This strategy and the alternative strategy of Illex to keep acidifying protons in the tissue may be important for the protection of hemocyanin function in the two species. PMID- 8342683 TI - Acute phase response in exercise. III. Neutrophil and IL-1 beta accumulation in skeletal muscle. AB - Nine untrained men (22-29 yr) performed 45 min of downhill running (16% incline, 70% of maximum heart rate). Needle biopsies of the vastus lateralis were performed before, 45 min after, and 5 days after exercise. Immunohistochemical staining of muscle cross sections revealed a 135% increase in muscle interleukin 1 beta (IL-1 beta) immediately after and a 250% increase (P < 0.03) 5 days after exercise. Using a rating scale (0-3) for the presence of neutrophils, light microscopic examination showed a significant accumulation of neutrophils in muscle biopsies taken 45 min after and 5 days after exercise [before: 0.5 +/- 0.2, 45 min after: 1.5 +/- 0.3 (P < 0.01), and 5 days after: 1.2 +/- 0.2 (P < 0.04)]. In addition, electron microscopic analysis showed an increase in the percentage of damaged Z-bands relative to total Z-bands [before: 4.8 +/- 3.5%, 45 min after: 32.5 +/- 8.6% (P < 0.05), and 5 days after: 14.1 +/- 3.2%]. Neutrophil accumulation was positively correlated to intracellular Z-band damage (rho = 0.66, P < 0.001). Immunohistochemical staining for IL-1 beta was related to neutrophil accumulation in muscle (rho = 0.38, P < 0.06) and to plasma creatine kinase levels (rho = 0.416, P < 0.04). These data indicate that after eccentric exercise ultrastructural damage to skeletal muscle is associated with neutrophil infiltration and muscle IL-1 beta accumulation. PMID- 8342684 TI - Volume-regulatory amino acid transport in erythrocytes of the little skate, Raja erinacea. AB - Skate erythrocytes swell in a hypotonic medium and then reduce their volume mainly by releasing the beta-amino acids taurine and beta-alanine. Although these amino acids exhibit a net efflux, Na(+)-independent influx is also increased. Both the reduction in cell volume and increase in amino acid transport are inhibited by several inhibitors of band 3-mediated anion transport, including 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) [L. Goldstein and S. R. Brill, Am. J. Physiol. 260 (Regulatory Integrative Comp. Physiol. 29): R1014 R1020, 1991]. The objective of the present investigation was to further characterize the mechanism of volume-activated amino acid transport. Na(+) independent amino acid uptake was studied because of the ease in controlling amino acid concentrations. Na(+)-independent taurine uptake was observed to be linear over a range of 0.1-15 mM and was not inhibited by 10 mM beta-alanine, suggesting that the transporter may be a channel rather than a carrier. The uptake of a variety of amino acids was examined to characterize the size of the putative channel. Glycine, beta-alanine, taurine, proline, gamma-aminobutyric acid (GABA), and threonine exhibited volume-activated transport that was DIDS inhibited, whereas aspartic acid, leucine, methionine, and ornithine were not transported. On the basis of the size of these amino acids, it appears that molecules containing eight or fewer major atoms and having a molecular mass of < 125-131 Da are transported during volume activation but larger molecules are not. We estimate the size of the channel to be 5.7-6.3 A in diameter. PMID- 8342685 TI - High blood pressure maintenance in transgenic mRen-2 vs. Lyon genetically hypertensive rats. AB - The present work was aimed to assess the factors involved in the maintenance of hypertension in adult transgenic mRen-2 (TG) rats. Special attention was paid to the renal handling of sodium, the sympathetic, and the renin-angiotensin system (RAS) activity. TG rats were compared with age-matched Lyon genetically hypertensive rats (LH), as both are of Sprague-Dawley origin. Blood pressure (BP), heart rate, and renal sympathetic nerve activity (RSNA) were recorded in conscious freely moving animals. Kidneys were isolated and single-pass perfused at different pressure levels. It was observed that the peripheral sympathetic drive was identical in TG and LH rats as indicated by their similar 24-h urinary excretion of catecholamines and methoxylated metabolites, baseline RSNA and its control by the baroreflex, and hypotensive response to ganglion-blockade. On the contrary, TG rats differed from LH rats by a more rapid excretion of an oral isotonic sodium load, a greater hypotensive and natriuretic response to furosemide, and a more marked BP response to acute RAS blockade. The TG kidney responses to stepwise changes in renal perfusion pressure (RPP) differed from those of LH rats by significantly higher perfusate flow and glomerular filtration rate. However, the pressure natriuresis curve of TG kidneys did not differ from that of LH rats because of an elevated tubular sodium reabsorption rate. These results suggest that adult TG rats, compared with LH rats, exhibit a tendency toward sodium and water retention, which may explain that despite low renal and circulating renin levels, the RAS remains involved in the maintenance of high BP in that model. PMID- 8342686 TI - Cerebrovasodilation elicited by fastigial stimulation is preserved under deep halothane anesthesia. AB - We studied the effect of halothane anesthesia on the increases in cerebral blood flow (CBF) and arterial pressure (AP) elicited by electrical stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized (0.75-2% halothane), instrumented for continuous recording of AP, and ventilated. The FN was stimulated through stereotaxically implanted microelectrodes. In CBF experiments the elevations in AP resulting from FN stimulation were eliminated by spinal cord transection at C1. After cord transection AP was maintained by intravenous phenylephrine. CBF or cerebral glucose utilization (CGU) was measured by laser Doppler flowmetry or the 2-deoxyglucose method, respectively. FN stimulation produced increases in CBF that were graded with the intensity (10-150 microA) or frequency (10-150 Hz) of stimulation. At 1% halothane, FN stimulation (100 microA; 75 Hz; n = 8) increased CBF by 123 +/- 16%. The elevations in CBF were attenuated by increasing levels of halothane anesthesia in a dose-dependent manner. At halothane concentrations of 1.5 and 2% the CBF response to FN stimulation (100 microA; 75 Hz) was reduced by 58 +/- 6 and 77 +/- 4%, respectively (p < 0.05 from 0.75% halothane; analysis of variance and Tukey's test). In contrast, the increases in CBF elicited by hypercapnia were not attenuated (P > 0.05 from 0.75% halothane). At 1% halothane, FN stimulation did not change CGU in neocortex (frontal cortex: unstimulated 48 +/- 6, mumol.100 g 1.min-1, FN stimulation: 47 +/- 11; P > 0.05; n = 5/group). In the group of rats in which the pressor response was studied (n = 7), halothane produced a dose dependent attenuation of the elevations in AP. The degree of attenuation of the AP response was comparable to that of the CBF response (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342687 TI - Carotid baroreflex control during hemorrhage in conscious and anesthetized dogs. AB - The hypothesis was tested that carotid baroreflex gain is increased after 20% hemorrhage. The baroreceptor reflex responses to changes in carotid sinus pressure (CSP) were measured in control, 20% hemorrhage, and reinfusion conditions in three experimental groups: conscious intact (n = 7), anesthetized intact (n = 8), and anesthetized vagotomized (n = 8) dogs. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and calculated total peripheral resistance (TPR) responses to changes in CSP were measured. At any given CSP, MAP, CO, and SV all decreased significantly with the 20% hemorrhage, as reflected by a downward shift in the reflex characteristic curve with no change in overall reflex range or gain. In contrast, TPR and HR responses to CSP were not significantly altered by 20% hemorrhage; reflex curves and gains were comparable to control conditions. In the conscious intact dogs, the maximal reflex gain, Gmax, for the MAP response was -1.365 +/- 0.25, -1.298 +/- 0.33, and -1.324 +/- 0.25 in control, 20% hemorrhage, and reinfusion conditions, respectively, and was not significantly altered by hemorrhage. In the same group, the Gmax for the HR response was -1.792 +/- 0.65, -1.709 +/- 0.33, and -1.986 +/- 0.67 in control, 20% hemorrhage, and reinfusion conditions, respectively; baroreflex gain on HR was not increased with hemorrhage. Plasma arginine vasopressin (AVP), an increase in which has been proposed to augment baroreflex gain, increased from a control level of 0.98 +/- 0.27 to 9.66 +/- 2.67 pg/ml during 20% hemorrhage in the conscious intact dogs; despite the increase in plasma AVP during hemorrhage, augmentation of baroreflex gain was not observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342688 TI - Hormonal, fluid, and electrolyte responses of sheep during chronic intravenous infusion of epidermal growth factor. AB - Epidermal growth factor (EGF) has been shown to increase water intake and urine volume. To further characterize these responses the effects of EGF on fluid balance, electrolyte, and hormone profiles were examined. After an 8-day control period, ewes received intravenous EGF at doses of 0 (n = 6), 2 (low dose, n = 6), 10 (medium dose, n = 6), or 20 micrograms/h (high dose, n = 5) for 4 days. During EGF treatment, water intake and urine volume increased (both P < 0.001) in a dose related fashion, although fluid balance was unaffected. Feed intake and fecal dry matter output were reduced (both P < 0.001) by the two higher doses of EGF. EGF had no effect on plasma potassium, sodium, or osmolality, but there was a dose related natriuresis (P < 0.001). Treatment with EGF increased plasma renin activity and aldosterone in the medium and high dose groups (both P < 0.001). Thus chronic intravenous infusion of 10-20 micrograms EGF/h into sheep caused polydipsia, polyuria, and natriuresis with neutral fluid balance. Whether the resultant polydipsia or polyuria was the primary response to EGF remains unclear. PMID- 8342689 TI - Chronic alcohol consumption increases sensitivity to the anorexic effect of cholecystokinin. AB - In this study we examined the ability of intraperitoneal cholecystokinin COOH terminal octapeptide (CCK-8; 0.2, 0.6, and 2.0 micrograms/kg) to suppress food intake in rats that had consumed a control diet, 6-8 g.kg-1.day-1 of ethanol (EtOH) in sucrose, or sucrose alone for 6 mo. Both the EtOH- and sucrose-fed rats developed significant dietary obesity. After 3 mo, the EtOH group was significantly more sensitive to CCK-8 than the sucrose and control groups, while the responses of the sucrose and control groups were comparable. In contrast, after 6 mo the EtOH and sucrose groups' response to CCK-8 was no longer significantly different. After 6 mo there were no significant differences in basal or postprandial plasma CCK-8 levels. The sucrose group had significantly higher basal insulin levels than the control and EtOH groups, and postprandial insulin levels, relative to basal, were significantly elevated in the EtOH group. Basal glucose levels did not differ among groups. Postprandial glucose levels (relative to baseline) were significantly lower in the EtOH group compared with the other groups and in fact never rose above baseline levels. These results are consistent with the hypothesis that EtOH, when taken on a chronic basis, increases the sensitivity to CCK-8. PMID- 8342690 TI - Integration of oral habituation and gastric signals in decerebrate rat pups. AB - During a series of oral infusions of a sweet solution, the ingestive responses of young rat pups habituate; pups stop responding to the infusions even when their stomachs are empty and the infused diet is nonnutritive. The rate of this oral habituation is enhanced by the addition of gastric fill signals, even in decerebrate pups. In intact but not in decerebrate pups, prior deprivation gates out the influence of gastric fill on habituation. This oral habituation system, responsive to multiple ingestion-related signals, may serve as the elemental process that integrates physiological state with ongoing behavior to control ingestion. PMID- 8342691 TI - Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs. AB - The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart. PMID- 8342692 TI - Effects of centrally and systemically administered indomethacin on body temperature in exercising rats. AB - Subcutaneous and intracerebroventricular (icv) injections of indomethacin were used to test whether prostaglandin synthesis is essential for the exercise induced increase in a rat's body temperature. At an air temperature of 24 degrees C, male Wistar rats ran on a treadmill at 10-15 m/min 20 min after 300-micrograms icv injection or 60 min after 15-mg/kg sc injection of indomethacin or of control vehicle. The rectal temperature (Tre) of control rats in 17 control experiments increased by 1.0 degree C during exercise, whereas the Tre of the rats pretreated with intracerebroventricular indomethacin increased by only 0.4 degrees C. Threshold Tre for tail vasodilation was significantly lower in rats pretreated with indomethacin than the control rats (38.4 +/- 0.1 vs. 38.9 +/- 0.1 degrees C), but O2 uptake did not differ between indomethacin-pretreated and control rats. Subcutaneous injection of indomethacin did not affect the body temperature, tail vasomotor activity, or O2 uptake of exercising rats. Intracerebroventricular indomethacin did not affect Tre or tail vasomotor activity of rats resting at ambient temperatures of 24 and 28 degrees C. Present results suggest that prostaglandin synthesis is required for the vasoconstrictive effect of exercise on skin blood vessels and thus for the exercise-induced elevation of body temperature. PMID- 8342693 TI - Meal-induced c-fos expression in brain stem is not dependent on cholecystokinin release. AB - Sprague-Dawley rats injected with a "physiological" dose of cholecystokinin octapeptide (CCK-8; 6 micrograms/kg ip) expressed c-fos immunoreactivity in the nucleus of the tractus solitarius (NTS) and the area postrema (AP) of the brain stem. Injection of the CCK-A antagonist L-364,718 30 min before CCK-8 injection eliminated c-fos expression in these regions. These findings support the hypothesis that CCK-8 induced c-fos expression is mediated by CCK-A receptors. We then tested whether a meal (Isocal) could activate c-fos, and, if so, whether this response could be eliminated by L-364,718. Ingestion of Isocal induced c-fos immunoreactivity in the NTS and AP. Meal-induced c-fos expression was not blocked by the CCK-A antagonist L-364,718. These findings demonstrate for the first time that a purely physiological nonnoxious stimulus, a meal, induces c-fos in the rat brain stem and indicate that feeding induces c-fos expression by a pathway that is largely, if not entirely, independent of CCK release. PMID- 8342695 TI - Glucagon and insulin regulate lipolysis in trout liver by altering phosphorylation of triacylglycerol lipase. AB - Rainbow trout were used to investigate the hormonal regulation by glucagon and insulin of hepatic triacylglycerol (TG) lipase activation. Two purified preparations of the trout hepatic TG lipase enzyme, the 110,000-g preparation and the resuspended ammonium sulfate fraction (ASF), were activated up to 58% with (in mM) 0.5 ATP, 0.01 cAMP, 5 MgCl2, and exogenous protein kinase over control levels. ATP or cAMP alone had no effect on activation. Activation of the trout hepatic lipase was reversible; complete inactivation of the ASF was obtained within 3 h in the presence of exogenous phosphorylase phosphatase. Adenosine 3',5'-cyclic monophosphate (cAMP)/ATP-dependent 32P-phosphorylation of trout hepatic lipase was observed within 5 min of incubation with the cAMP/ATP-Mg2+ activation system and 25 microCi [32P]ATP. Hormonal modulation of trout hepatic lipase phosphorylation was studied in isolated hepatocytes. Hepatocytes were incubated with [32P]-monopotassium phosphate for 3 h, then exposed to mammalian glucagon (GLU). Within 5 min, increased lipolysis was accompanied by a 95% increase in phosphorylation of the enzyme. Mammalian insulin (INS) depressed GLU stimulated phosphorylation by 56% and inhibited GLU-stimulated lipolysis. These results indicate that GLU and INS modulate lipolysis in trout liver by altering phosphorylation of the TG lipase enzyme. PMID- 8342694 TI - Reanalysis of the rat proestrous LH surge by deconvolution analysis. AB - To evaluate the temporal mechanisms that give rise to the spontaneous proestrous surge of luteinizing hormone (LH) in the rat, we have applied deconvolution analysis to earlier immunoreactive LH concentration vs. time profiles obtained by sampling blood in proestrus at 2- to 3-min intervals in 10 animals over a span of 160-300 min. Six other animals were bled in 6-min intervals on day 1 of diestrus. Deconvolution analysis permitted us to calculate the number, duration, amplitude (maximal release rates), and mass of underlying LH secretory bursts and to simultaneously estimate basal secretion and the half-life of endogenous LH in each animal. Proestrus rats exhibited a significant increase in the number of computer-identified LH secretory bursts per hour (1.8 +/- 0.2 vs. 1.1 +/- 0.01 on diestrus, P < 0.01), with a corresponding reduction in the LH intersecretory burst interval from 61 +/- 6.4 min (diestrus) to 25 +/- 2.7 min (proestrus, P < 0.01). There was a remarkable 16-fold increase in the mass of LH secreted per burst, which rose from 72 +/- 5.2 to 1,230 +/- 200 ng/ml (P < 0.01). This resulted from a sixfold increase in LH secretory burst amplitude and a doubling of burst duration. The total amount of LH released in a burstlike fashion during the proestrous LH surge rose 20-fold, and calculated basal LH secretion increased to approximately 25% of this value. Of interest, the computed half-life of endogenous LH also increased from 10 +/- 1.1 to 19 +/- 3.7 min (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342696 TI - The circadian melatonin and cortisol secretion pattern in permanent night shift workers. AB - In permanent night shift workers the impact of environmental time cues on the circadian system is conflicting. Rhythm adjustments to the nocturnal work schedule have been described, and their significance for tolerance to shift work is under discussion. Reports concerning the effect of this work situation on the setting of the endogenous clock are, however, inconsistent. We examined nine healthy young male permanent shift workers with high work satisfaction at the end of a week on night work and seven male controls with normal diurnal working hours. All subjects were admitted to a research facility for 28 h, and blood was collected with a continuous-withdrawal pump in portions taken hourly for the estimation of the circadian melatonin (MT) and cortisol secretion pattern. One control did not exhibit a circadian secretion pattern. When compared with the other controls (n = 6), all except one of the shift workers showed no difference in the phase or phase relationship of their hormonal profiles. In the shift workers, a minor trend toward elevation of the MT amplitude and an increase in two indicators for the amount of MT secreted were noticed. One individual displayed inverse hormone rhythms with an undisturbed phase relationship of MT and cortisol and inconspicuous hormone amplitudes. He showed, however, an inverse day-night rhythm in his private life, too. The data collected suggest that even permanent night workers with a high degree of work satisfaction do not usually lose the diurnal orientation of their endogenous clock. Factors other than reorientation of the circadian system may be more important for high tolerance to shift work. PMID- 8342697 TI - Somatic and visceral inputs to neurons of the rostral ventrolateral medulla. AB - Sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM) play an essential role in the generation of basal sympathetic tone and in the reflex regulation of blood pressure. In this study responses of RVLM "cardiovascular" neurons to somatic and visceral afferent stimulation were investigated. The activity of 34 RVLM neurons was recorded in urethan-anesthetized paralyzed and artificially ventilated rats. These neurons were identified as cardiovascular based on their baroreceptor sensitivity and their pulse-synchronous discharge. Electrical stimulation of the sciatic nerve excited 31 of the 34 RVLM units (91%). Renal nerve stimulation inhibited firing of 14 of 22 RVLM neurons tested (64%), not affecting the remaining 8 units. Stimulation of splenic nerves inhibited the discharge of 7 of 12 RVLM neurons tested (58%), whereas the remaining 5 units were not affected. All RVLM units responsive to visceral afferent stimulation were also responsive to sciatic nerve stimulation. These results indicate that RVLM cardiovascular neurons receive somatic and visceral inputs, suggesting an involvement of these units in the integration of homeostatic responses to changes in the internal and external environment. PMID- 8342699 TI - Anoxia-tolerant hepatocytes: model system for study of reversible metabolic suppression. AB - Chrysemys picta bellii is well known for its ability to survive extended anoxic periods and has been widely used as a model system to study anoxic metabolism. Described here is a method for the isolation of anoxia-tolerant hepatocytes from this species. Freshly isolated hepatocytes were determined to be viable based on trypan blue exclusion, gluconeogenic capacity from [14C]lactate, responsiveness to epinephrine and glucagon, and maintenance of cellular adenylate concentrations. Under anoxic conditions for 10 h there was no significant increase in cell staining and no decrease in cellular ATP concentration. Furthermore, the addition of cyanide at the 5-h mark did not result in any significant differences in these parameters; however, iodoacetate added at this time caused trypan blue staining to increase and ATP concentrations to fall. The rate of glucose production from the cells was threefold greater under anoxic than normoxic conditions, underscoring the important role of the liver in supplying substrate during anoxia. From the rate of O2 consumption and rate of lactate production under anaerobic conditions, ATP turnover rates were calculated to be 68.4 +/- 7.2 and 6.5 +/- 0.43 mumol ATP.g-1.h-1, respectively; this corresponds to a 90% decrease in metabolic rate during anoxia. Within a cellular system such as this the more complex regulatory mechanisms involved in a large coordinated reduction in metabolism can be probed. PMID- 8342698 TI - Response of protein synthesis to anoxia and recovery in anoxia-tolerant hepatocytes. AB - Hepatocytes from the western painted turtle (Chrysemys picta bellii) display a profound metabolic suppression under anoxia. Fractional rates of protein synthesis fell by 92% during 12 h anoxia at 25 degrees C and were indistinguishable from the rate obtained with cycloheximide. Normoxic recovery saw protein synthesis increase to 160% of control values and return to normal after 2 h. The GTP-to-GDP ratio, implicated in the control of translation, fell threefold during anoxia. Purine nucleotide phosphate profiles suggest that this change occurs through increasing concentrations of ADP and GDP, with concentrations of ATP and GTP and total purines remaining constant. The normoxic cost for protein synthesis was calculated at 47.6 +/- 6.8 mmol ATP/g protein. Normoxic protein synthesis accounted for 36% of overall ATP turnover rates, close to the extent of O2 consumption inhibitable by cycloheximide (28%). Under anoxia, the proportion of ATP turnover utilized by protein synthesis did not change significantly. ATP turnover rates for urea synthesis reflected a similar pattern, falling 72% under anoxia. These results reflect the cell's ability to suppress protein synthesis under anoxia in a manner that is coordinated with the reduction in total metabolic rate. PMID- 8342700 TI - Angiotensin-converting enzyme inhibition and Na appetite: microbehavioral analysis and nycthemeral physiology. AB - The present experiments describe a marked nycthemeral rhythm in both the appetite for 0.3 M NaCl solution and components of the renin-angiotensin-aldosterone axis stimulated in Sprague-Dawley rats by chronic administration of enalapril, an angiotensin I-converting enzyme inhibitor. Continuous recording of water, NaCl, and food intakes shows that the sodium appetite is manifest as discrete bouts of salt ingestion in temporal proximity to meals and is partially independent of water bouts. In particular, salt bouts occur without water bouts in the late afternoon of a 12:12-h light-dark cycle and continue periprandially with water bouts during the night. Intake of all three commodities is minimal in the morning. In a second experiment, it was determined that plasma renin activity (PRA) was maximally elevated by chronic enalapril in the daytime and that plasma aldosterone was reduced by enalapril but continued to show nycthemeral rhythm peaking in the afternoon. The concurrent maxima in PRA and aldosterone in the afternoon in enalapril-treated rats thus coincides with NaCl intake in the absence of water intake. PMID- 8342701 TI - Effect of elevated atrial pressure on plasma renin activity in hypotensive fetal lambs. AB - In adults, renin secretion is stimulated by reductions in arterial pressure and inhibited by increases in atrial pressure. In the late gestation fetus, a fall in arterial pressure stimulates renin secretion, but it is unknown whether elevation of atrial pressure will alter such an increase. Therefore we studied the effect of elevated atrial pressure on renin secretion in the presence of nitroprusside induced arterial hypotension. Thirteen fetal lambs at 127.9 +/- 0.9 days of gestation were prepared 5 days before study with inflatable pulmonary artery occluders and right atrial, vascular, and amniotic catheters. Each fetus underwent two protocols (hypotension and hypotension with occlusion) using a randomized block design. Nitroprusside reduced arterial pressure by 34% in both groups. Right atrial pressure during the course of hypotension was significantly higher in the occlusion group (F = 14.2, P = 0.001). Plasma renin activity increased similarly in both groups during hypotension (F = 6.0, P = 0.003). Elevated right atrial pressure did not alter hypotension-induced renin secretion in the fetus. PMID- 8342702 TI - Endothelin-induced natriuresis and diuresis are pressure-dependent events in the rat. AB - The goal of the current study was to determine the mechanism by which doses of endothelin (ET) that do not markedly affect the glomerular filtration rate (GFR) cause a natriuresis and diuresis. ET was infused into pentobarbital-anesthetized female rats at 50 ng.kg-1.min-1 iv for 30 min. In controls (n = 6 rats; n = 5 in all other groups), ET increased mean arterial blood pressure (MAP) from 95 +/- 2 to 131 +/- 2 (SE) mmHg, Na excretion (UNa V) from 0.34 +/- 0.07 to 1.83 +/- 0.2 meq/min, and urine flow rate (V) from 13 +/- 1 to 24 +/- 3 ml/min (all P < 0.01 vs. baseline). At 15 min during infusion of ET, the GFR was not affected (2.1 +/- 0.1 to 2.2 +/- 0.1 ml/min) but modestly decreased to 1.8 +/- 0.1 ml/min at 30 min (P < 0.05 vs. baseline). Either removing the capsule from both kidneys during surgery or maintaining renal arterial pressure at baseline values with an adjustable clamp on the aorta above the right renal artery abolished the ET induced increase in UNa V and V. Meclofenamate also did not alter the ET-induced increase in MAP, V, or UNa V. To determine the intrarenal site of action of ET, experiments were conducted with ET plus amiloride or with a combination of amiloride plus furosemide; there was a larger ET-induced diuresis and natriuresis in amiloride-treated rats and an even larger response with amiloride plus furosemide compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342703 TI - Effect of outflow pressure on lymphatic pumping in vitro. AB - The objective of this study was to determine how lymphatic vessels responded to outflow pressure changes in vitro. Bovine mesenteric lymphatics were suspended in an organ bath preparation with both inflow and outflow ends cannulated. Input to the duct was provided from a reservoir filled with Krebs solution. To initiate pumping, a transmural pressure was applied to the ducts by elevating the fluid reservoir and outflow catheters and making their heights equal to one another. The outflow catheter was then elevated above the liquid in the reservoir in 2 cmH2O increments, and pumping activity was monitored for 10 min at each outflow pressure. Outflow pressures were calculated as the product of the flow rate and outflow cannula resistance plus the height of the tip of the outflow catheter above the liquid in the organ bath. At low transmural pressures (2-4 cmH2O), elevations in outflow pressure often had little effect on flow rates until high outflow pressures had been attained. In contrast, elevations in outflow pressures resulted in an increasingly rapid decline in flow rates as transmural pressures were incrementally increased. The mean power (in mu W) required to produce the observed flow rate was estimated at each outflow pressure as the product of the flow rate and the pressure across the lymphatic vessel. The ability of the lymphatics to generate sustained or enhanced power output in response to an increasing outflow pressure challenge was most pronounced at lower transmural pressures. As transmural pressures were increased, the range of outflow pressures that stimulated increased power production was diminished. We conclude that elevations in outflow pressure in an in vitro preparation result in a nonlinear decline in flow rates. This nonlinearity is due to an active lymphatic pump mechanism. PMID- 8342704 TI - On the site of loss: a response to Antokeletz's paper on cross-cultural transformation. PMID- 8342705 TI - The psychoanalysis of ethnicity and the ethnicity of psychoanalysis. I. PMID- 8342706 TI - The negative therapeutic reaction, maternal transference, and obsessions. PMID- 8342707 TI - Occupational hazards and characterological vulnerability: the problem of "burnout". PMID- 8342708 TI - An alternative to the "traumatizing" vacation: the enriching, expansive vacation. PMID- 8342709 TI - Analysis interminable reconsidered. PMID- 8342710 TI - Prenatal weight gain and postpartum weight retention: a delicate balance. PMID- 8342711 TI - Improving cause-of-death statistics: the case of fetal deaths. PMID- 8342712 TI - Analyzing socioeconomic and racial/ethnic patterns in health and health care. PMID- 8342713 TI - The coding of underlying cause of death from fetal death certificates: issues and policy considerations. AB - Recently, plans to implement nationwide coding of underlying cause of fetal death have been promulgated. To examine the validity and potential utility of nationwide coding, this paper presents data from a five-state (Wisconsin, Arkansas, Maine, North Carolina, California) analysis of underlying causes of fetal death from vital records for 1985 through 1987. Nosological coding rules varied somewhat from state to state. Underlying causes were grouped into categories; distributions were similar for each state. Many deaths (20.3% to 32.9%) were coded as unspecified conditions. Congenital anomalies accounted for only 6.9% to 10.3% of fetal deaths, including implausible and nonspecific causes. In total, 29.5% to 42.8% of the reports were not valid or useful. To obtain better data, researchers must focus on improving fetal death reporting, which will entail the promotion of comprehensive autopsy, placental and laboratory evaluation, systematic vital records query procedures, and implementation of multiple-cause-of-fetal-death coding. PMID- 8342714 TI - Over-the-counter oral contraceptives--an immodest proposal? PMID- 8342715 TI - Should oral contraceptives be available without prescription? AB - In this paper, it is argued that oral contraceptives should be available without prescription. Prescription status entails heavy costs, including the dollar, time, and psychological costs of visiting a physician to obtain a prescription, the financial and human costs of unintended pregnancies that result from the obstacle to access caused by medicalization of oral contraceptives, and administrative costs to the health care system. After a review and evaluation of the reasons for strict medical control of oral contraceptives in the United States, safety concerns anticipated in response to the proposal discussed here are addressed. Also, concerns that prescription status is necessary for efficacious use are evaluated. It is concluded that neither safety nor efficacy considerations justify prescription status for oral contraceptives. Revised package design and patient labeling could allow women to screen themselves for contraindications, to educate themselves about danger signs, and to use oral contraceptives safely and successfully. Several alternatives to providing oral contraceptives by prescription with current package design and labeling and selling them over the counter are suggested; the proposals discussed would make these safe and effective contraceptives easier to obtain and to use. PMID- 8342716 TI - Pregnancy-related weight gain and retention: implications of the 1990 Institute of Medicine guidelines. AB - OBJECTIVES: Guidelines from the Institute of Medicine's 1990 report call for weight gains during pregnancy that are higher than those previously recommended. This study examines the potential implications of compliance with these guidelines for postpartum weight retention. METHODS: Weight retention 10 to 18 months following delivery was examined for selected women who had live births in the 1988 National Maternal and Infant Health Survey. Women's actual weight gains during pregnancy were retrospectively classified according to the Institute of Medicine's guidelines. RESULTS: Weight retention following delivery increased as weight gain increased, and Black women retained more weight than White women with comparable weight gain. The median retained weight for White women who gained the amount now being recommended was 1.6 lb whereas that for Black women was 7.2 lb. CONCLUSIONS: If pregnant White women gain weight according to the institute's guidelines, they need not be concerned about retaining a substantial amount of weight postpartum. Our findings suggest, however, that Black women are in need of advice about how to lose weight following delivery. PMID- 8342717 TI - Factors influencing the practice of vaginal birth after cesarean section. AB - OBJECTIVES: Vaginal birth after cesarean has been recommended for most women with previous cesarean sections for the past 10 years. This practice, however, has not yet been generalized because high variations can still be observed among countries, hospitals, and physicians. METHODS: A case-control study involving 635 case patients and 2593 control patients was carried out to determine which characteristics of the physician, the patient, or the hospital were important in the adoption of this practice. RESULTS: The results of the multiple stepwise logistic regression analysis indicate a higher likelihood that women will experience vaginal birth after cesarean if their physicians had cesarean rates under 20%, had less than 5% of their patients considered at risk, and were younger than 54 years old. Vaginal birth after cesarean was also favored by hospitals characterized by a high degree of neonatal and obstetrical specialization, and a patient population with a low level of education. CONCLUSIONS: This policy is still in the developmental stage, as evidenced by the great variability between hospitals and physicians in rates of vaginal birth after cesarean. Further efforts are required for this policy to become the norm. PMID- 8342718 TI - Variation in cesarean section rates among hospitals in Washington State. AB - OBJECTIVES: This study examined hospital characteristics and hospital population risk factors and their associations with hospital-specific cesarean section rates in Washington State. METHODS: Data were obtained from 1987 birth certificates. The study population included all hospitals that had 12 or more singleton live births. RESULTS: Hospital-specific cesarean section rates varied from 0% to 43% and were positively associated with proprietary ownership, size of delivery service, and the proportions of women who had complications or high-birthweight infants. The proportion of women who had late prenatal care was inversely associated with cesarean section rates. Although proprietary hospitals had higher cesarean section rates, their patient populations were lower risk than patients of public or teaching hospitals. CONCLUSIONS: Variation in cesarean section rates among hospitals cannot be fully explained by either hospital or patient population characteristics. A combined strategy may be necessary to lower unjustifiably high cesarean section rates. PMID- 8342719 TI - Oral contraceptives and the risk of gallbladder disease: a meta-analysis. AB - OBJECTIVES: This study was designed to assess the risk of gallbladder disease due to oral contraceptive use by conducting a thorough literature review. METHODS: Controlled epidemiologic studies published through March 1992 were systematically searched and evaluated. Of 25 studies (27 publications), 9 could stand the test of critical appraisal with respect to validity. Restriction to these studies was judged to circumvent publication bias at the same time. RESULTS: Oral contraceptive use is associated with a slightly and transiently increased rate of gallbladder disease. The results of six selected studies in which asymptomatic women were screened for gallstones were strikingly similar. Pooling of these results yielded an odds ratio, for ever vs never oral contraceptive use, of 1.36. A dose-effect relationship was indicated, suggesting that modern low-dose oral contraceptives are safer than older formulas, but an effect cannot be excluded. CONCLUSIONS: Considering the large efforts already devoted to this exposure disease relationship, the probably weak effect, and the rapidly changing formulas of oral contraceptives, the authors suggest that the safety of new oral contraceptives be evaluated by studying bile saturation and biliary function rather than by waiting for gallbladder disease to develop. PMID- 8342720 TI - Smoking and pregnancy outcome: trends among black teenage mothers in Missouri. AB - OBJECTIVES: The purpose of this study is to analyze the smoking changes that have occurred among pregnant Black teenagers in Missouri. The study also examines changes in Black teenage pregnancy outcomes in relation to smoking behavior changes. METHODS: This analysis used computerized data files from the 1978 to 1990 Missouri birth certificates to acquire information on smoking during pregnancy for 41,544 Black teenagers and 105,170 White teenagers. All Missouri births with smoking history were included in the study. RESULTS: During the study period, the rate for Blacks who smoked during pregnancy decreased from 37% in 1978 to less than 22% in 1990. A large part of this reduction is attributable to Black teenagers, whose smoking-during-pregnancy rate declined from 35.8% to 7.2%. Additionally, the Black teenage-specific low-birthweight rate decreased by 13.6% over the study period, possibly influenced by the decrease in smoking. CONCLUSIONS: The results indicate that a major norm has changed in smoking status among pregnant Black teenagers. Understanding the reasons behind this change could assist smoking cessation and other health promotion efforts. PMID- 8342721 TI - Epidemiologic evidence for a potentiating effect of malnutrition on child mortality. AB - OBJECTIVES: Despite broad agreement that severe malnutrition contributes to child mortality in developing countries and that malnutrition has a physiologically synergistic relationship with morbidity, evidence of an epidemiologic synergism has been lacking. Also, the literature provides conflicting evidence concerning the existence of elevated mortality among children with mild to moderate malnutrition. A review of published population-based studies of anthropometry mortality relationships was undertaken to clarify these relationships. METHODS: Six studies with the relevant data were reanalyzed to test for synergism and elevated mortality in mild to moderate malnutrition. RESULTS: The results demonstrate that mortality increases exponentially with declining weight for age. This effect is consistent across studies and there is no apparent threshold effect on mortality. The primary difference across studies is in baseline levels of mortality, which determine the quantitative impact of malnutrition on mortality in a population. CONCLUSIONS: These results indicate that mild to moderate malnutrition is associated with elevated mortality and that there is an epidemiologic synergism between malnutrition and morbidity. This previously undemonstrated finding has significant implications for child survival policies and research. PMID- 8342722 TI - Vietnamese infant and childhood mortality in relation to the Vietnam War. AB - OBJECTIVES: There is obvious potential for war to adversely affect infant and childhood mortality through direct trauma and disruption of the societal infrastructure. This study examined trends in Vietnam through the period of the war. METHODS: The 1988 Vietnam Demographic and Health Survey collected data on reproductive history and family planning from 4172 women aged 15 through 49 years in 12 selected provinces of Vietnam. The 13,137 births and 737 deaths to children younger than age 6 reported by the respondents were analyzed. RESULTS: For the country as a whole, infant and childhood mortality dropped by 30% to 80% from the prewar period to the wartime period and was stable thereafter. In provinces in which the war was most intense, mortality did not decline from the prewar period to the wartime period but declined after the war, consistent with an adverse effect during the wartime period. CONCLUSIONS: The data are limited by assignment of birth location on the basis of mother's current residence and by inadequate information on areas of war activity. Nonetheless, the data do not indicate a widespread, sizable adverse effect of the war on national infant and childhood mortality in Vietnam but suggest detrimental effects in selected provinces. PMID- 8342723 TI - Sexual behavior and exposure to HIV infection: estimates from a general population risk index. AB - OBJECTIVES: The spread of the human immunodeficiency virus (HIV) in the general population has been a much debated topic in the mass media. The aim of this study was to create an approach to estimating the risk of exposure to HIV resulting from sexual behaviors. METHODS: A theoretical estimate was applied to data obtained from a large-scale risk factor survey carried out in Britain. An HIV infection-exposure risk index was constructed by ranking different sex-related categorizations derived from variables in the survey. RESULTS: The risk index involved a Delphi-based assessment of self-reported behavioral factors associated with HIV exposure and subsequent transmission. Roughly 85% of the adult population aged 18 to 50 were estimated to be at some risk for behavioral exposure to HIV virus with regard to reported sexual behavior. Over time, those who could be considered at no risk have declined as a proportion of the population. CONCLUSIONS: The estimates appear to refute commonplace assertions that exposure to HIV through sexual behavior is not a problem for general populations. PMID- 8342724 TI - HIV risk-related sex behaviors among injection drug users, crack smokers, and injection drug users who smoke crack. AB - OBJECTIVES: This study was designed to assess and compare sex risk behaviors for human immunodeficiency virus (HIV) transmission of three drug user groups: injectors who do not smoke crack, crack smokers who do not inject, and injectors who also smoke crack. METHODS: Sexual risk behaviors for HIV were assessed among 246 drug users from Denver, Miami, and San Francisco. Respondents were classified into the three drug groups based on self-report and verified through urinalysis and physical inspection. RESULTS: An increased risk for HIV through sexual transmission was associated with crack cocaine use, particularly among those who also injected. Crack smoking injectors were more likely to report sex with an injector, exchanging sex for drugs and/or money, drug use before or during sex, and unprotected sexual intercourse. They also injected more than injectors only, smoked crack as often as smokers only, and reported higher overall frequencies of drug use. CONCLUSIONS: These findings, together with the higher rates of gonorrhea and syphilis reported by smokers and injectors/smokers, are indicators of the risk crack poses for the heterosexual transmission of HIV. PMID- 8342725 TI - Frequent cocaine users and their use of treatment. AB - OBJECTIVES: Despite decreases in the number of cocaine users since 1985, the consequences of cocaine use continue to rise. This paper provides descriptive data on frequent cocaine users that will help to explain these diverging trends and enable treatment planners to better predict the types of cocaine users who are likely to seek treatment. METHODS: Data from the National Household Survey on Drug Abuse were used to study the characteristics of frequent cocaine users since 1985. The 1991 data were used to compare frequent users with infrequent users and nonusers. RESULTS: Since 1985, frequent cocaine users have become older. In 1991, they were likely to be unemployed (32.4%), unmarried (82.3%), and without health insurance (39.4%). Most were cigarette smokers (86.8%) and marijuana users (88.4%), and 32.0% reported getting drunk weekly. Criminal behavior was more likely among frequent cocaine users than among frequent cocaine users than among infrequent users and nonusers. Almost a third (30.0%) reported drug abuse treatment experience in the past year. CONCLUSIONS: Despite the recent decreases in overall prevalence of cocaine use, the need for treatment of cocaine abusers will continue. Treatment must address multiple problems that occur in conjunction with cocaine abuse. PMID- 8342726 TI - Lead content in 70 brands of dietary calcium supplements. AB - OBJECTIVES: Elevated lead levels in calcium supplements may pose a health risk, particularly to children with milk intolerance who rely on these products to meet their calcium requirement. Earlier reports chiefly focused on the lead content in supplements derived from bonemeal and dolomite. This study undertook to determine the lead levels in the major forms of calcium supplements currently available. METHODS: The lead content was measured in 70 brands of calcium supplements grouped in the following five categories: dolomite, bonemeal, refined and natural source calcium carbonate, and calcium chelates. RESULTS: The lead levels measured in the supplements ranged from 0.03 microgram/g to 8.83 micrograms/g. Daily lead ingestion rates revealed that about 25% of the products exceeded the US Food and Drug Administration's "provisional" total tolerable daily intake of lead for children aged 6 years and under. Less than 20% of the supplements had "normalized" lead levels comparable to or lower than that reported for cow's milk. CONCLUSIONS: Children are the most sensitive to the low-level effects of lead. If calcium supplements are to provide an alternate source of calcium to some of these individuals, they should also deliver concomitant lead dosages no greater than those obtained from milk products themselves. PMID- 8342727 TI - Changes in energy intakes during pregnancy and lactation in a national sample of US women. AB - Increases in energy intakes during pregnancy and lactation were evaluated by examining dietary data for 458 pregnant women who participated in the Continuing Surveys of Food Intakes by Individuals conducted in 1985 and 1986. Energy intakes were well below recommendations during all reproductive states; however, increases during pregnancy approximated recommendations, while increases during lactation were low. Postpartum non-lactating intakes did not return to prepregnancy levels for Black women or women with lower incomes. PMID- 8342728 TI - The quality of the new birth certificate data: a validation study in North Carolina. AB - A random sample of 395 December 1989 North Carolina birth certificates and the corresponding maternal hospital medical records were examined to validate selected items. Reporting was very accurate for birth-weight, Apgar score, and method of delivery; fair to good for tobacco use, prenatal care, weight gain during pregnancy, obstetrical procedures, and events of labor and delivery; and poor for medical history and alcohol use. This study suggests that many of the new birth certificate items will support valid aggregate analyses for maternal and child health research and evaluation. PMID- 8342730 TI - Fatal car fires from rear-end crashes: the effects of fuel tank placement before and after regulation. AB - A federal standard for fuel tank integrity in cars was applied to 1977 and subsequent models. National data indicate that fatalities per 10,000 occupants in rear-end crashes of small cars, where fire was the most harmful event, were reduced by approximately 57% if the fuel tank was located behind the rear axle and 77% if the tank was situated directly above or in front of the rear axle. PMID- 8342729 TI - Mandating vitamin K prophylaxis for newborns in New York State. AB - New York State's infant deaths and hospitalizations attributed to hemorrhagic disease of the newborn and other neonatal hemorrhagic conditions were reviewed. In 65% of 34 deaths reviewed, vitamin K was not documented as given or was given only after the onset of hemorrhage. Vitamin K was not included in standing orders in any of 22 hospitals contacted. As a result of this review, vitamin K prophylaxis was made a mandatory newborn care procedure in the State Public Health Code. PMID- 8342731 TI - Black leaders' perceptions of the year 2000 public health goals for black Americans. AB - We surveyed 1196 Black health and political leaders on their perceptions about the US Department of Health and Human Services' Healthy People 2000 public health goals. Respondents identified reducing the incidence of acquired immunodeficiency syndrome, improving maternal and infant health, and controlling sexually transmitted diseases as the three most important public health goals for Black Americans that are amenable to intervention. The leaders assigned nearly all responsibility for prevention efforts to the federal government and the individual. With the American health care system now in flux, Black leaders need to organize to see that these priority issues are addressed. PMID- 8342732 TI - Community hospitals can increase staff influenza vaccination rates. PMID- 8342733 TI - The Hawaii pneumococcal disease initiative. PMID- 8342734 TI - Maternal reporting of birthweight in a Peruvian shanty town. PMID- 8342735 TI - Socioeconomic and racial differences in obstetric procedures. PMID- 8342736 TI - The ramifications of induced abortion. 1. The unbroken chain of life. PMID- 8342737 TI - Abortion in the Eastern Bloc, then and now. PMID- 8342738 TI - How safe is the consumption of trona? PMID- 8342739 TI - Position paper: Immunotherapy with hymenoptera venoms. (EAACI) The European Academy of Allergology and Clinical Immunology. PMID- 8342740 TI - Position paper: Allergen standardization and skin tests. The European Academy of Allergology and Clinical Immunology. PMID- 8342741 TI - Position paper: Immunotherapy. PMID- 8342742 TI - [Interleukin-1 beta and interleukin-6-plasma concentrations in laparotomies. Interaction with neuroendocrine secretion and postoperative temperature regulation?]. AB - Elevated body temperature, increased plasma cortisol concentrations, and loss of the circadian secretory pattern are typical changes observed after trauma and surgery. We investigated the hypothesis that the interleukins IL-1 beta and IL-6 are involved in these phenomena, since both are endogenous pyrogens and can induce ACTH and cortisol secretion. METHODS. Eight healthy women undergoing hysterectomy for non-malignant diseases participated in the study after having given written consent. The study had the approval of our institution's ethics committee. Anaesthesia was induced with fentanyl 0.1 mg and methohexitone 1.5 mg/kg and maintained with isoflurane in 60% N2O and 40% O2. Blood samples were drawn before induction, before incision, during surgery, at the end of surgery, and 30, 60, 120, 240 and 360 min after surgery. Cortisol, prolactin, IL-1 beta, and IL-6 concentrations were determined with commercially available ELISAs. Statistical analysis was performed with non-parametric methods. RESULTS. IL-6 increased significantly from 15 (4.3-23) to 68 (18-107) pg/ml (medians and range) at the end of surgery and peaked at 128 (52-214) pg/ml 60 min postoperatively (p < 0.01, Table 2). Baseline IL-1 beta concentrations were 20 (1-35) pg/ml with a significant increase in median postoperative concentrations in the postoperative period (p < 0.001). Prolactin increased from 22 (13-43) to 210 (115-291) ng/ml immediately after induction of anaesthesia (p < 0.001) and remained elevated until 240 min after surgery. Cortisol increased from 99 (26-167) to 384 (241-553) ng/ml during surgery and reached a maximum of 475 (246-597) ng/ml 30 min postoperatively (Table 3). Rectal and mean body temperatures increased significantly in the postoperative period (Table 1). There was a significant correlation between IL-6 and cortisol concentrations (r = 0.468; p < 0.001), but none was found between IL-6 and temperature or between IL-1 beta and cortisol or temperature. CONCLUSIONS. Surgical trauma markedly stimulates the secretion of IL 6, and to a lesser extent that of IL-1 beta. The data do not yield any evidence indicating an effect of IL-1 beta or IL-6 on body temperature. Postoperative prolactin concentrations might be influenced by IL-6. The positive correlation between plasma concentrations of IL-6 and cortisol may be coincidental, but could reflect a causal relationship, particularly in the postoperative period during which time the circadian pattern of cortisol secretion is disturbed. PMID- 8342743 TI - [The cardiotoxicity of bupivacaine during pacemaker stimulation is dependent on the stimulation frequency. Results of an experimental study]. AB - The cardiotoxic effects of bupivacaine are related to the temporal dispersion of effective refractory periods in different parts of the cardiac conduction system. This effect facilitates the occurrence of re-entry arrhythmias under burst stimulation [4, 8]. In this study physiological increments in heart rate were simulated by cardiac pacing, and the electrophysiological and haemodynamic effects under the influence of cardiotoxic concentrations of bupivacaine were measured. METHODS. After institutional approval we generated cardiotoxic arterial plasma concentrations of bupivacaine (6.9 +/- 1.6 micrograms/ml) in pigs (n = 8; 15-22 kg) by i.v. injection of 4 mg bupivacaine/kg, followed by a constant rate infusion of 0.2 mg/kg per min [8]. The pigs were anaesthetized with midazolam, fentanyl and pancuronium and normoventilated with a FiO2 of 0.4. Internal right atrial and right ventricular pacing was performed with increasing frequencies of 20, 40, 60, 80 and 100 stimulations/min above individual spontaneous heart rates (AL) before (control) and after the administration of bupivacaine. ECG, MAP, LVSP, dp/dtmax and stimulation thresholds were recorded. Student's t-test, and the U-test of Wilcoxon, Mann and Whitney were used for statistical testing with a significance level of 0.05. RESULTS. By inducing a frequency-dependent increase in stimulation threshold, bupivacaine prevented regular atrial pacing with frequencies higher than AL + 60. Ventricular pacing with a frequency of AL+40 induced a lethal arrhythmia in 1 animal. In the remaining 7 pigs ventricular pacing showed a frequency-dependent increase in stimulation thresholds (Fig. 1) and stimulus-QRS intervals (Fig. 5). MAP (Fig. 2), LVSP (Fig. 3) and cardiac inotropy (Fig. 4) showed frequency-dependent decreases under ventricular pacing. CONCLUSIONS. The toxic effects of bupivacaine on pacing thresholds, av conduction, intraventricular conduction, cardiac inotropy, and blood pressure are modulated by the stimulation frequency of a cardiac pacemaker. The cardiotoxic effects of bupivacaine seem to be use dependent. Even minor increments in heart rate can induce malignant arrhythmias. Cardiac pacing can be difficult in the presence of toxic bupivacaine concentrations, and high-frequency pacing should be avoided. It has to be verified whether higher heart rates generated by the physiological pacemakers of the heart do also increase the cardio-circulatory toxicity of bupivacaine. If that holds true, drugs that can induce tachycardias should be avoided in the treatment of bupivacaine toxicity. PMID- 8342744 TI - [Emesis and the oculocardiac reflex. Drug prophylaxis with droperidol and atropine in children undergoing strabismus surgery]. AB - Although droperidol is often used to prevent emesis, vomiting is still common in children undergoing strabismus surgery. METHODS. One hundred children aged 3 to 12 years admitted for strabismus surgery were enrolled in a randomised, double blind study to investigate the influence of the timing of the administration of droperidol (75 micrograms/kg i.v.) and the effect of atropine (10 micrograms/kg i.v.) on postoperative vomiting and the occurrence of the oculocardiac reflex (OCR). Each child was prospectively assigned to one of the following groups: Group A: atropine and droperidol before the beginning of surgery (n = 25); Group B: atropine before the beginning, droperidol after completion of surgery (n = 25); Group C: no atropine, droperidol before the beginning of surgery (n = 25); Group D: no atropine, droperidol after completion of surgery (n = 25). After oral premedication with 0.4 mg/kg midazolam, anaesthesia was induced via a face mask by inhalation of halothane, nitrous oxide, and oxygen and 1 mg/kg succinylcholine was given to facilitate tracheal intubation. Gastric contents were aspirated by a gastric tube at the end of the operation. Vomiting and retching were recorded for 24 h; recovery from anaesthesia was assessed by a modified Steward score. RESULTS. The four groups were comparable regarding age, sex, body weight, duration of anaesthesia, and number of repaired eye muscles. Patients receiving droperidol before and after the end of surgery had a similar incidence of vomiting (groups A and C 60% vs. groups B and D 50%). There was no significant difference in the number of patients vomiting between groups A and B (58%) and groups C and D (52%). The incidence of the OCR was lower in the patients premedicated with atropine (18% vs. 60%, P < 0.01). There was no statistical relationship between the occurrence of the OCR and post-operative emesis. Younger children (3 to 6 years) vomited more often than older ones (7 to 12 years). The incidence of the OCR was higher in patients with more than two eye muscles repaired than in others. Recovery scores were slightly lower in patients with droperidol after completion of surgery; postoperative recovery times did not differ significantly between the study groups. CONCLUSIONS. The timing of the administration of droperidol (75 micrograms/kg) had no influence on postoperative vomiting. The application of atropine (10 micrograms/kg) prior to surgery did not influence vomiting after strabismus surgery. Atropine (10 micrograms/kg) reduced the incidence of the OCR significantly. There was no statistical relationship between the occurrence of the OCR and postoperative vomiting. PMID- 8342745 TI - [Extracorporeal shock-wave therapy (ESWT) for pseudoarthrosis. A new indication for regional anesthesia]. AB - Extracorporeal shock-wave therapy for the treatment of pseudarthrosis is a new indication for anaesthesia. In a clinical trial of 65 treatments in 53 patients, the anaesthetic procedure is shown. Regional anaesthesia, mainly plexus blocks of the upper and lower extremities, was performed in nearly all cases. The various localisations of the pseudarthroses and the types of anaesthetic techniques used are shown in Table 1. In all, we performed 9 epidural blocks, 2 spinal blocks, 29 axillary blocks, 3 supraclavicular perivascular blocks (Winnie), 1 psoas compartment block, and 20 sciatic/femoral 3-in-1 blocks. The shock waves used for this therapy are several times stronger than those used for nephrolithotripsy. Furthermore, the shockwaves are focused on bone and periosteum, which is abundantly innervated. Therefore, in contrast to nephro-lithotripsy with second generation lithotripters, anaesthesia must be performed for this therapy. We chose regional anaesthesia for several reasons: the procedures are located in the arms or legs, which can readily be anaesthetised by regional blocks. The duration of treatment ranged up to several hours. By using regional anaesthesia, we were able to avoid unnecessary exposure to general anaesthetics. Finally, most of the patients wanted to stay awake during the new treatment and therefore opted for regional techniques. A typical set-up for the treatment is shown in Fig 1. In 67% of the patients fracture healing was significantly improved by the new therapy. Acceptance of therapy and anaesthesia by the patients was very good. PMID- 8342746 TI - [The performance of respirator alarms during simulated critical events in CMV/IPPV artificial respiration]. AB - Alarm systems of ventilators enhance detection of possible critical events during artificial ventilation. Due to their significance, in some countries the alarm detection of ventilators is regulated by federal law. Up to now, no recommendations for the adjustment of alarm limits exist and only a few detailed investigations of the accuracy of alarm detection are available. METHODS. The response of four commercially available ventilators (Servoventilator 900C, Siemens, Inc.; Bennett 7200a, Hoyer, Inc.; Veolar, Hamilton, Inc.; EVITA, Drager, Inc.) to critical events during artificial ventilation of a test lung were evaluated. We measured the alarm time (the time between event creation and alarm response) of ten different simulated critical events including disconnection, differentisized leaks, failure of the gas supply, and obstruction at different places in the artificial airway. DISCUSSION. All respirators were able to recognise severe critical situations such as hose disconnection, failure of gas supply, and total airway obstruction within a short time (< 15 s). The recognition of small airway leaks was more difficult for the ventilators even when the alarm thresholds were close. The alarm detection of the EVITA (software 10.0 or less) under conditions of partial airway obstruction may be a source of risk for the patient as the machine continued supplying inspiration with pressure limited ventilation even when the pressure threshold was reached. PMID- 8342747 TI - [Perioperative cardiovascular reactions and the noradrenaline plasma level in patients on chronic antidepressant medication]. AB - It is still controversial whether the perioperative incidence of cardiovascular complications is increased in patients on chronic treatment with cyclic antidepressants (AD) and whether AD medication should be discontinued prior to surgery. METHODS. We measured perioperative cardiovascular variables in 31 patients on chronic treatment with tri- and tetracyclic AD and 31 patients without AD medication. Heart rate, blood pressure, and noradrenaline plasma concentrations were compared between the two groups at nine points in time. During induction of anaesthesia, the ECG was recorded continuously. After the administration of 0.01 mg/kg atropine i.v., all patients received opiate supplemented enflurane anaesthesia. RESULTS: Re-uptake inhibition of noradrenaline by AD resulted in significantly higher noradrenaline plasma concentrations before and during anaesthesia in the AD-treated group. The incidence of arrhythmias, blood pressure elevations, and tachycardia was not increased in patients in AD treatment. Arrhythmias during induction of anaesthesia were seen in 6 of the AD-treated patients and 5 of the controls. Blood pressure elevations by more than 35% were seen in 10 patients on AD treatment and 8 controls. The heart rate prior to induction of anaesthesia and 2 h after the end of surgery was significantly higher in the AD-treated group. During anaesthesia the heart rate was higher at two points in time only. The incidence of tachycardia was similar in both groups. Intravenous administration of 0.01 mg/kg atropine prior to induction of anaesthesia increased the heart rate of the patients on chronic AD medication by 11.4%. This increase was significantly higher in the control group (16.2%), suggesting that patients with chronic AD treatment do not have a higher sensitivity to atropine. CONCLUSION: The elevated noradrenaline plasma levels in patients on chronic AD treatment did not result in a higher incidence of arrhythmias, blood pressure elevations, or tachycardia perioperatively. Taking these results into account, we do not consider it necessary to discontinue chronic AD medication prior to surgery in patients without cardiovascular disease. PMID- 8342748 TI - [Damage to a stent caused by a Shaldon catheter]. AB - Recently, stent implantation has been used with increasing frequency in the treatment of central venous stenoses in patients undergoing chronic haemodialysis. Stent localisation may interfere with central venous catheterisation. CASE REPORT. In a 57-year-old female haemodialysis patient, a filiform stenosis of the right subclavian vein was treated by percutaneous transvenous angioplasty and stent implantation. Five weeks later, she presented with a thrombosed dialysis shunt. A Shaldon catheter was implanted via the right internal jugular vein. Post-procedure radiographs showed extensive stent damage without stent dislocation or thrombosis. CONCLUSION. Stent localisation has to be considered in the event of later central venous catheterisation. Venous puncture should be carried out under fluoroscopic control if catheter placement on the side of the stent is inevitable. PMID- 8342749 TI - [A difficult intubation: prolapse of the epiglottis into the trachea in an infant]. AB - Luxation of the epiglottic cartilage is a very uncommon complication of endotracheal intubation in paediatric anaesthesia. We report on a case of prolapse of the epiglottic cartilage into the trachea in a 4-month-old child who had been anaesthetized for palliative banding of the pulmonary artery and correction of a coarctation of the aorta. Further malformations included a single ventricle combined with an ASD II and VSD. The first intubation (ID 3.5 mm) via the nasopharyngeal route seemed not to involve any problems; breathing pressure, however, increased to 25 cm H2O. Direct laryngoscopy after extubation of the smaller tube and insertion of another one (ID 4.0 mm) demonstrated a completely blocked trachea. The epiglottidean cartilage had prolapsed into the tracheal lumen and excluded any possibility of ventilating the patient. After seizing the epiglottic cartilage with a Magill forceps it was possible to pull the cartilage out of the trachea and to intubate again with the 4.0 mm tube. There were no complications in the postoperative period. PMID- 8342750 TI - [Fulminant pulmonary embolism in the 35th gestational week. Sonographic detection of a thrombus in the inferior vena cava with normal cavography]. AB - Pulmonary embolism is the most common cause of maternal death during pregnancy. CASE REPORT. We report a 28-year-old obstetric patient (35th gestational week) who was admitted to the hospital because of intermittent vaginal bleeding caused by placenta totalis et accreta. Eleven days after admission she suffered a cardiac arrest. After cardiopulmonary resuscitation, an emergency caesarian section was performed and a healthy child was delivered. Abdominal sonography (B mode) showed a floating thrombus in the inferior vena cava. Perfusion scintigraphy and cavography were normal; a computed tomography i.v. contrast medium study confirmed the presence of the thrombus. An open thrombectomy was performed to protect the patient from further pulmonary emboli. After 8 days she left the intensive care unit without residual complications. CONCLUSION. This case emphasises the importance of bedside sonography as a diagnostic method of identifying the source of a thrombus in patients with suspected pulmonary embolism. PMID- 8342751 TI - [The effect of sedation on oxygen uptake during spontaneous breathing]. AB - Sedation may be used in intensive care and emergency medicine to improve the oxygen demand/delivery ratio. The influence of sedation has most frequently been investigated in a dose-related manner. The aim of the present study was to determine the effect-related influence of different sedatives on oxygen uptake (VO2) in relation to defined resting conditions. METHODS. Forty ASA I patients who had to undergo a minor surgical procedure were investigated 1.5 h before surgery at basal energy-expenditure measurement conditions. One of the following substances was given with a preset bolus rate in a double-blind, randomised order until a defined level of sleep or side effects was encountered: propofol (n = 8), midazolam (n = 8), thiopentone (n = 8), sodium chloride (n = 8), and fentanyl (n = 8). The sleep level was defined as sluggish response to a loud voice or tapping on the forearm. The variables VO2, carbon dioxide elimination (VCO2), end tidal CO2 (p(et)CO2), oxygen saturation (SaO2), heart rate, systemic blood pressure, skin temperature, and skin resistance on the sole of the foot were documented on line on a computer. All variables were compared using differences of averages from 10-min periods before and after sedation during which the VO2 was minimal. RESULTS. The mean VO2 before sedation was 264 +/- 60 ml/min, and the measured energy expenditure did differ by -0.2% (+/- 14%) from mean predicted values using the Harris-Benedict equation. The VO2 was reduced by 15 +/- 2% with propofol, by 12 +/- 8% with midazolam, and by 10 +/- 5% with thiopentone. This was statistically significant compared to placebo treatment, as was the difference between propofol and thiopentone effects. All patients in these groups reached the defined sleep level, which was not achieved by the placebo and fentanyl groups. Placebo treatment changed the VO2 by 0.1% (+/- 2%). Fentanyl increased the VO2 by 5% (+/- 8%), which did not reach significance. In the fentanyl group the bolus application had to be stopped at a p(et)CO2 of 50 mm Hg in all patients. In the propofol, midazolam, and thiopentone groups the phasic changes of skin resistance were reduced to zero and the skin temperature increased from 27 +/- 2 degrees C to 32 +/- 2 degrees C. The fentanyl group showed an increase in changes of skin resistance without changes in temperature. CONCLUSIONS. Sleep induced by propofol, midazolam, or thiopentone to a clinically maximal desirable level in spontaneously breathing patients reduced VO2 by 10% to 15%. This level of sedation did not induce a relevant change in P(et)CO2 or SaO2. The effect of propofol appeared to be the most pronounced and least variable. This may be attributable to a more pronounced reduction in single-organ VO2 or to an undetected difference in level of sedation. Fentanyl did, in contrast to most publications on opioid effects, seem to increase VO2. Underlying mechanisms may be sought in an increased rate-pressure product and sympathetic activity on the basis of hypercapnia and changes in muscle tension. PMID- 8342752 TI - [Respirators in intensive care medicine. Fundamentals]. AB - Microprocessor-controlled intensive care ventilators combine controls of pressure, flow, volume, and timing to generate various breathing modes and differentiated breathing patterns that will meet the respiratory needs of the patient. This is essential when respirator-supported ventilation is performed. Graphic representation of ventilatory parameters is another important feature, facilitating subtle adjustments. The future may bring even more desirable options to improve monitoring of respiratory mechanics and make management easier. Modern ventilators differ less in technical features than do the accessories with different options. Most of these options are costly without any corresponding benefit in terms of treatment or diagnosis; nevertheless, future upgrading possibilities should be borne in mind when hardware is purchased. There is no ideal ventilator, and the success of respiratory treatment will therefore continue to be dependent on the patient's underlying disease and the therapist's level of training and experience rather than on the choice of respirator. PMID- 8342754 TI - Disk submissions. PMID- 8342753 TI - Clover's nitrous oxide/ether inhaler 1876. PMID- 8342755 TI - The Sprotte needle and post dural puncture headache following caesarean section. AB - One hundred and forty-four patients receiving subarachnoid anaesthesia for caesarean section were prospectively analysed for quality of anaesthesia and the occurrence of post dural puncture headache (PDPH). Anaesthesia was administered via 24 gauge Sprotte (n = 104) and 26 gauge Quincke (n = 40) needles using hyperbaric bupivacaine 0.5% with morphine 0.2 mg. Anaesthesia was successful in 103 patients with the Sprotte needle and 38 patients with the Quincke needle, and the operating conditions were considered to be excellent. Of the 104 patients in the Sprotte needle group there were ten with PDPH (9.6%), two of which were considered severe. Of the 40 patients in the Quincke needle group there were eight with PDPH (20%), three of which were considered severe. Despite the lower incidence of headache in the Sprotte needle group, this was not statistically significant (P > 0.05), due to the difference in population size. We conclude that the 24 gauge Sprotte needle is associated with a comparatively low but clinically relevant incidence of headache in the obstetric population. PMID- 8342756 TI - Epidural catheter insertion: the effect of saline prior to threading in non obstetric patients. AB - The effects of injecting normal saline 4 ml through the epidural needle before catheter passage on ease of catheterisation and incidence of certain complications were investigated in 189 non-obstetric patients. The use of saline had no effect on ease of catheterisation, with 84.2% of Group S patients (saline, n = 95) and 88.3% of Group C patients (control, n = 94) having the difficulty of passing the catheter rated as "easy" (P = 0.31). The incidence of complications was not affected by the use of saline. Paraesthesia occurred in 27.4% of Group S patients compared with 16.0% of Group C patients (P = 0.08). Epidural venous cannulation occurred in 6.3% of Group S patients versus 11.7% of Group C patients (P = 0.30). We conclude that the use of 5 ml of normal saline prior to catheter threading provides no significant benefit in improving the ease of catheterisation or decreasing the incidence of catheter complications. PMID- 8342757 TI - Apnoea and oximetric desaturation in patients receiving epidural morphine after gastrectomy: a comparison of intermittent bolus and patient controlled administration. AB - The number of apnoeic episodes and arterial oxygen desaturations were measured preoperatively and for sixty hours postoperatively in twenty ASA status 1-2 patients scheduled for elective gastrectomy. Monitoring included continuous pulse oximetry, respiratory inductive plethysmography and repeated arterial blood gas analysis. The number and magnitude of apnoeas and desaturation episodes were compared between two postoperative analgesic regimens of epidural morphine; intermittent bolus injection (Group B, n = 10), and patient controlled administration with continuous infusion (Group P, n = 10). Morphine dose, P(a)CO2 and mean SpO2 values were similar between the two groups. Although the number of central apnoeas with SpO2 < 90% was greater in Group B, other episodes of apnoea or desaturation were similarly seen preoperatively. In the postoperative period, central apnoeas with SpO2 < 90% were significantly increased in Group B, while no change was seen in Group P. Apnoeas with SpO2 < 80% were only seen in Group B. We conclude from these results that postoperative apnoeas and episodic desaturations are greatly influenced by the different modes of opioid administration. PMID- 8342758 TI - A rabbit model for the evaluation of epidurally administered local anaesthetic agents. AB - A rabbit model is described for the evaluation of epidurally administered local anaesthetic agents. The technique involves a single injection via the readily identified lumbosacral space in conscious rabbits, with the epidural space being identified by a modified loss-of-resistance technique. The endpoints used to assess pharmacodynamic responses of the rabbit model were (1) sensory loss, (2) loss of weight-bearing ability, and (3) flaccid paresis. The model was further characterised by investigation of endpoint responses to changes in injection volume (0.1-0.25 ml/kg) and concentration of administered lignocaine solutions (0.5 to 2%). From these studies, a volume of 0.2 ml/kg was chosen as a standard dose and a subsequent comparison between different agents undertaken. The rank order for the onset of action, duration of effect and the observed pharmacokinetic profiles after epidural administration of 2% lignocaine, 2% lignocaine with adrenaline (1:200,000) or 0.5% bupivacaine solutions are broadly consistent with human clinical data. These data indicate that the rabbit is a simple (albeit limited) model for the screening evaluation of epidurally administered local anaesthetic agents. PMID- 8342760 TI - The influence of obesity on the relationship between body mass index and the distance to the epidural space from the skin. AB - This study confirms that distance to the epidural space from the skin at the L3-4 interspace is only moderately correlated with body mass index in obstetric patients. A similar moderate linear correlation was found in the non-obstetric patients. However, in obese patients (BMI > 25), distance to epidural space from the skin correlated poorly with body mass index. PMID- 8342759 TI - A comparison of effects of fixed and tailored cardiopulmonary bypass flowrates on renal function. AB - Cardiopulmonary bypass may result in renal impairment but there is little investigative data on the effect of differing flowrates on postoperative renal function. One hundred and twenty-two patients presenting for cardiac surgery were randomly assigned to receive either a fixed CPB flow of 2.4 l.m-2 or a bypass flow tailored to maintain a venous return oxygen saturation of 75-80%. Vasoactive drugs were given to maintain a perfusion pressure of 50 to 80 mmHg. Patients were assessed by serum creatinine, creatinine clearance, arterial blood gases, serum lactates and electrolytes. The results show an overall decline in postoperative renal function compared with preoperative levels, with no significant differences between the two groups. PMID- 8342761 TI - A review of anaesthesia for ruptured abdominal aortic aneurysm with special emphasis on preclamping fluid resuscitation. AB - Ruptured abdominal aortic aneurysm (RAAA) remains a critical emergency with an average hospital mortality of 50%. There has been no significant improvement in survival despite advances in anaesthesia, surgery and intensive care over the last 30 years. It is believed that early diagnosis, aggressive surgical management and meticulous attention to haemodynamic status and coagulation may improve survival, but this is unsubstantiated. Mortality is closely linked to the degree of preoperative hypotension and other related factors such as massive blood transfusion and cardiac arrest. Survival depends not only on the severity of rupture, but also the ability to compensate physiologically, and is linked to the premorbid state of the patient. Management priorities are dictated chiefly by the clinical signs and symptoms at presentation. There is controversy regarding the appropriate preoperative fluid regimen for RAAA. PMID- 8342762 TI - Parental attitudes to presence at induction of paediatric anaesthesia. AB - Previous studies of parental presence at induction of anaesthesia in children have examined parental reaction to being present and the benefits gained from their presence. This study was undertaken specifically to assess parents' attitudes to being present at induction of their child's anaesthetic. A total of 154 questionnaires were distributed over a two-week period to parents of children presenting to the Day Stay Unit for procedures requiring general anaesthesia. Eighty-eight percent would have liked to be present at induction. Only 41% of parents expected to be present and only 40% of parents were actually present for their child's induction. Of those parents present, 94% felt it helpful to their child, 65% helpful to themselves and 41% helpful to the anaesthetist. No-one felt their presence to have been unhelpful. These results may provide an incentive for anaesthetists to review their current paediatric anaesthetic practices. PMID- 8342763 TI - "Don't turn the needle!". AB - Accidental dural puncture is a well-recognised complication of epidural anaesthesia. The technique of inserting the epidural needle with the bevel parallel to the spinal ligaments is still taught in some centres. Evidence is presented that the subsequent turning of the needle to allow passage of the epidural catheter may increase the likelihood of dural puncture. There would also appear to be a greater chance of subdural catheterisation. The epidural needle should be introduced with the bevel in the direction in which the catheter is to go and not moved once the epidural space is located. PMID- 8342764 TI - Quality assessment in personal anaesthetic practice. AB - Continuing education can improve anaesthetic practice if it is relevant to an individual's work and complications. A practice profile delineates the significance of untoward events. A personal audit of consecutive anaesthetics and associated complications is presented as a first step to checking one's competence over the course of years. PMID- 8342765 TI - A fatal reaction following scavenged autologous blood transfusion. PMID- 8342766 TI - A comparison of three ported cannulae available in New Zealand. AB - A comparison was made of the three 22-gauge ported intravenous cannulae available in New Zealand--Venflon 2, Vasofix Braunule and Insyte. All cannulae performed satisfactorily in terms of overall success of cannulation although significant differences were apparent in both clinical and laboratory performance. Anaesthetists' clinical preference was for Insyte and Venflon 2 brands, perceiving these to have greater ease of handling and better packaging. In a series of laboratory studies, Vasofix was found to have the highest flowrate, the fastest time to flashback and the lowest valve opening pressure. Insyte required the least force of penetration. Venflon 2 had the greatest margin of safety between pressure to inject through the port and pressure required to blow the syringe/port assembly apart. Potential problems were identified with the Insyte port valve mechanism. PMID- 8342767 TI - Massive intraoperative pulmonary thromboembolism treated by pulmonary embolectomy. PMID- 8342768 TI - Sudden onset unilateral pulmonary oedema during thoracotomy. PMID- 8342769 TI - Transoesophageal echocardiography aids insertion and management of the "Thoratec" ventricular assist device. PMID- 8342770 TI - Acute dapsone poisoning. PMID- 8342771 TI - Upper limb amputation following radial artery cannulation. PMID- 8342773 TI - Clinical prediction of a difficult intubation. PMID- 8342772 TI - The diagnosis of fatal anaphylactic reactions during anaesthesia: employment of immunoassays for mast cell tryptase and drug-reactive IgE antibodies. PMID- 8342774 TI - Postoperative amiodarone pulmonary toxicity. PMID- 8342775 TI - Central anticholinergic syndrome following reversal of neuromuscular blockade. PMID- 8342776 TI - Cardiac and respiratory complications of mediastinal lymphomas. PMID- 8342777 TI - Airway obstruction with a cuffed single-use plastic endotracheal tube. PMID- 8342778 TI - Total oesophageal obstruction in association with combined enteral feed and sucralfate therapy. PMID- 8342780 TI - Eye movement during cataract surgery. PMID- 8342779 TI - Artefact with rate-responsive pacemaker. PMID- 8342781 TI - Failure of insulin mixing in 10% glucose. PMID- 8342782 TI - Phantom sensation. PMID- 8342784 TI - The flexible, reinforced tube LMA--initial experience. PMID- 8342783 TI - Ephedrine and caesarean section. PMID- 8342785 TI - Taping ETT connectors. PMID- 8342786 TI - Flow injection chemiluminometric determination of epinephrine, norepinephrine, dopamine and L-dopa. AB - A method is proposed for the determination of 0.0500-1.00 microgram ml-1 of epinephrine and L-dopa and 0.100-1.00 micrograms ml-1 of norepinephrine and dopamine by their chemiluminogenic oxidation with potassium permanganate in acidic medium, in the presence of formaldehyde, which greatly improves the sensitivity. Flow injection allows the measurement of 80 solutions per hour. The method was also optimized for a continuous-flow system. Comparative results from numerous organic compounds proved the necessity for electron-donating groups on the benzene ring for sensitive chemiluminescent characteristics. PMID- 8342787 TI - Continuous-flow chemiluminometric determination of tetracyclines in pharmaceutical preparations and honey by oxidation with N-bromosuccinimide. AB - A continuous flow chemiluminometric method for determining 0.050-3.00 micrograms cm-3 of tetracycline, 0.50-5.00 micrograms cm-3 of oxytetracycline, 0.50-7.00 micrograms cm-3 of doxycycline and chlorotetracycline and 0.30-3.00 micrograms cm 3 of demeclocycline in pharmaceutical preparations and honey is described. The method is based on the chemiluminescence produced by the action of N bromosuccinimide on tetracyclines in alkaline solution. The emission intensity is greatly enhanced by the presence of ammonia. The procedure is automated and solutions can be analysed at a rate of 130 h-1 with a relative error of about 2%. During evaluation of possible interferences of the method, recoveries from solutions with common excipients and other concomitant compounds were in the ranges 97.8-104.0 and 96.6-109.4%, respectively. Recoveries of various tetracyclines from commerical formulations and honey samples were in the ranges 95.2-103.7 and 89.2-106.6%, respectively. The results obtained for the assay of commerical pharmaceutical preparations compared well with those obtained by an official method and demonstrated accuracy and precision (< or = 5%). PMID- 8342788 TI - Expression of alkaline phosphatase in the mature mouse placenta visualized by in situ hybridization and enzyme histochemistry. AB - Alkaline phosphatases (APs) are a family of cell surface glycoproteins that are expressed in a variety of tissues. Their physiological functions are still unclear. Three different AP genes have been found to be expressed in mice, and AP cloned from the placenta is of the tissue non-specific (TNAP) type. We have in investigated the location of TNAP mRNA and active AP in mature mouse placenta, using in situ hybridization and enzyme histochemistry on serial sections. Digital image analysis was used to estimate relative amounts of TNAP mRNA. Tissue non specific alkaline phosphatase messenger was detected only in the placental labyrinth, whereas active AP was present both in the labyrinth and in a zone of cells at the margin of the decidua basalis, bordering the myometrium and the metrial gland. This latter location of AP activity has not been described previously. The AP-positive zone of the decidua had a condensed appearance and a central defect in the zone was visible on sections taken from the middle of the placenta. No TNAP messenger was found in the zone of AP-positive decidual cells. PMID- 8342789 TI - An immunohistochemical study of basic fibroblast growth factor in the developing chick. AB - An antiserum against basic fibroblast growth factor (bFGF) was characterized by immunoblot experiments and used to investigate immunohistochemically the appearance of bFGF-like immunoreactivity in the developing chick. Crude homogenates of chick embryos at every developmental stage, when subjected to immunoblotting with the use of bFGF antiserum, exhibited a main band with the same molecular weight (18 kDa) as bovine bFGF. With immunohistochemistry, bFGF immunoreactivity (bFGF-IR) was detected exclusively in intracellular components of various tissues at different stages of development; bFGF-IR appeared initially on embryonic (incubation) day 3 (E3) in the myotome, on E12 in the spinal cord and ganglia, on E8 in chondrocytes and osteoblasts of the vertebrae, and on E10 in the esophageal epithelium. Immunoreaction products were present either in the cytoplasm or in the nuclei, depending on the types of individual bFGF-containing cells; developing chondrocytes and cells in the stratum basale of the esophagus exhibited intense immunoreactions exclusively within the nuclei, and the other cells mainly within the cytoplasm. Moreover, bFGF-IR was observed in discrete regions of these tissues at different stages; the epithelium of the esophagus contained bFGF-IR in all layers on E10 to E18 with a superficial-to-basal gradient, but it began to exhibit bFGF-IR only in the stratum basale after E20; and bFGF-IR was more abundant in hypertrophic chondrocytes than in proliferating ones. As chicks aged, bFGF-IR decreased or disappeared in the muscles, vertebrae and esophageal epithelium, but neuronal bFGF increased in intensity until the perinatal period and thereafter remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342791 TI - Dorsal rhizotomy does not alter rat estrous cycles or ovarian compensatory responses. AB - Rats were subjected to right side dorsal rhizotomy of spinal nerves T12-L2 and ipsi- or contralateral unilateral ovariectomy at estrus (day 1). Estrous cycles were recorded daily, and on day 15 the remaining ovary was removed and weighed. Antral follicles were counted in representative day 1 and day 15 ovaries. Dorsal rhizotomy did not affect estrous cycles during the period after surgery. Also dorsal rhizotomy did not alter ipsilateral ovarian hypertrophy or follicular activation following unilateral ovariectomy. Thus, although the major portion of the ovarian sensory innervation is via the lesioned segments, interruption of these segments centrally does not alter compensatory ovarian responses subsequent to unilateral ovariectomy. PMID- 8342790 TI - Tissue variation of two large chondroitin sulfate proteoglycans (PG-M/versican and PG-H/aggrecan) in chick embryos. AB - PG-M and PG-H, chick large chondroitin sulfate proteoglycans corresponding to versican (fibroblast-type proteoglycan) and aggrecan (cartilage-characteristic proteoglycan), respectively, which are found in mammals, have been characterized in various tissues of chick embryos. Their distribution and the compositions of the core molecules were analyzed by immunofluorescence staining and immunoblotting, respectively, using various monospecific antibodies. Molecules reactive to a monoclonal antibody to the PG-M core protein (designated MY-174) were distributed in various tissues, including aorta, lung, cornea, brain, skeletal muscle and dermis. Immunoblotting with MY-174 of the chondroitinase ABC digested tissue extracts showed a tissue variation of MY-174-reactive core molecules (550-kD, 500-kD, 450-kD, and 350-300-kD). In contrast, PG-H, besides massive occurrence in cartilage, was only found in a few tissues such as aorta and brain. In addition, PG-H in aorta, cornea, and skin was atypical in structure, because it lacked keratan sulfate. The expression of PG-M in developing chick embryos was then examined. PG-M was found in some developmentally active areas, such as the perinotochordal mesenchyme between notochord and neural tube, the basement membranes facing neuroepithelial cells, and condensing mesenchymal cells in limb buds, suggesting some functions distinctive of the developing tissues. PMID- 8342792 TI - Visualization of lectin-like proteins in human placenta by means of anti-plant lectin antibodies. AB - Proteins antigenically cross-reactive with lectins were sought in the placenta by immunohistochemistry using polyclonal antibodies raised in rabbit against four well-known lectins: Concanavalin A, Wheat germ agglutinin, Ulex europaeus agglutinin, and Phaseolus vulgaris leukoagglutinin (PHA-L), as well as one antibody raised in goat against PHA-L. Even at high dilutions of the primary antibody, strong staining was obtained after short incubations, in patterns generally resembling those obtained for placental lectins by other means, such as those based on binding capacity for glycosylated probes. One of the immunohistochemical patterns distinguishes with great clarity between the trophoblast cell layers, thus relating to developmental and functional parameters; another localises PHA-L-immunoreactivity to the syncytiotrophoblast. These results underline the validity of the immunohistochemical screening as an approach in its own right. Both positive and negative controls were applied to the immunohistochemical methodology. These controls showed that the staining patterns obtained relate to the specificities of the primary antibodies employed; i.e. to lectins. The PHA-L-like cross-reactivity was analysed immunochemically. In electrophoretically separated and Western-blotted placental extracts there were found anti-PHA-L-binding fractions of apparent molecular weights 30 kDa, 58 kDa and 67 kDa. Control studies of the PHA-L antigen showed anti-PHA-L-binding fractions of approximate molecular weights 32 kDa and 60 kDa. The 30 kDa fraction from placenta and the 32 kDa fraction from PHA-L antigen bound lactosylated BSA but not fucosylated BSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342793 TI - Differentiation of the gonads and initiation of mammary gland and scrotum development in the brushtail possum Trichosurus vulpecula (Marsupialia). AB - The first appearance of the mammary and scrotal primordia and the sexual differentiation of the gonads of the brushtail possum, Trichosurus vulpecula, are described. Primordial germ cells were first observed, in fetuses of 7.5 mm crown rump length, in the gonadal ridges and migrating up the dorsal mesentery. Mammary primordia were first observed in fetuses of 11 mm, and scrotal primordia in those of 12 mm crown-rump length. These structures were diagnostic of female and male brushtail possums respectively. Processus vaginales and gubernacula showed sexual dimorphism, being better developed and appearing earlier in males than in females. Sexual differentiation of the gonads occurred after the appearance of mammary and scrotal primordia, the testes being first recognisable in a 14.5-mm fetus and the ovaries postnatally. Birth occurred between the stages of 14 and 15 mm crown-rump length. These observations appear to indicate that the development of mammary and scrotal primordia are not under gonadal hormonal control, but under direct genetic control, as suggested for the tammar wallaby by previous authors. PMID- 8342794 TI - Onset of gastrulation, morphogenesis and somitogenesis in mouse embryos displaying compensatory growth. AB - This is a study on the ability of mouse embryos to compensate for a loss of cells and to develop with body parts of normal size and normal proportions during post implantation development. Micro-manipulations were performed on 4-cell pre implantation mouse embryos to reduce the number of cells by 25% (3/4 embryos) or 50% (2/4 embryos). Blastocysts developed from these embryos showed a preferential loss of inner cell mass population, and fewer of them formed viable embryos after implantation. The size of post-implantation 3/4 embryos was initially smaller than controls of the same gestational age, but compensatory growth, achieved by increasing cell numbers at above the normal rate and beyond the normal duration, took place between 6.5 and 11.5 days, resulting in a complete restoration of body size. During compensatory growth the 3/4 embryos rescheduled events of gastrulation and morphogenesis in keeping with cell number or body size appropriate for each developmental stage. The formation of the correct number of somites was accomplished by changing the rate of somite segmentation and by an adjustment of the size of individual somites and somitomeres proportional to the available amount of precursor tissues. Morphogenesis and pattern formation in embryos recovering from earlier cell losses are therefore regulated in accordance to tissue volume (or cell number) instead of chronological age or some intrinsic cellular clock. PMID- 8342796 TI - Should we use muscle biopsy to diagnose malignant hyperthermia susceptibility? PMID- 8342795 TI - Tissue culture of bovine subcommissural organ. AB - Tissue of the secretory, glial subcommissural organ (SCO) of adult, male cattle was cultured in serum-free medium for 70 days in vitro. Only minor alterations in the histoarchitecture and the cytology of the explanted SCOs could be observed by light and electron microscopy. Light- and electron-microscopic immunocytochemical investigations with an antiserum raised against bovine SCO secretory proteins revealed intra- and extra-cellularly localized immunoreactive material in tissue sections of SCO explants cultured up to 69 days in vitro. An indirect competition enzyme-linked immunosorbent assay (ELISA) was developed to detect minor quantities of SCO secretory products. By means of this assay, approximately 35 ng RF protein per ml was detected in culture medium supernatants conditioned for 3 days in SCO tissue cultures at 3, 38, and 69 days in vitro. These studies demonstrate that the bovine SCO can maintain its secretory activity throughout long periods in vitro. PMID- 8342797 TI - Intraoperative transesophageal echocardiography for the detection of cardiac preload changes induced by transfusion and phlebotomy in pediatric patients. AB - BACKGROUND: Intraoperative blood volume changes are difficult to monitor in pediatric patients. The authors tested the hypothesis that transesophageal echocardiography would identify changes in cardiac filling resulting from manipulations of blood volume. METHODS: Eleven patients (3-15 kg) were studied following sternal closure after repair of congenital heart lesions. Transesophageal echocardiography of the midpapillary left ventricular short axis view and hemodynamics were recorded at baseline (T1), during withdrawal of blood until the systolic blood pressure decreased by 5 mmHg (T2) and 10 mmHg (T3), and after reinfusion of the blood (T4). The identical cycle of blood withdrawal and reinfusion was repeated after administration of calcium chloride (10 mg/kg; T5 T8). RESULTS: Manually traced transesophageal echocardiography images of the left ventricular end-diastolic area decreased from 4.64 +/- 1.50 cm2 at T1 to 4.03 +/- 1.25 cm2 at T2 to 3.78 +/- 1.35 cm2 at T3, and increased to 4.42 +/- 1.75 cm2 at T4. Nearly identical results were obtained at T5-T8. End-systolic areas significantly decreased from 1.96 +/- 0.86 cm2 at T1 to 1.52 +/- 0.73 cm2 at T2 to 1.41 +/- 0.62 cm2 at T3, and increased to 1.87 +/- 0.88 cm2 at T4. An experienced anesthesiologist-echocardiographer blinded to study events was able to identify mild reductions in blood volume (T2, T3, T6, T7) from recorded cine loop video recordings with high sensitivity (80-95%) and specificity (80%). CONCLUSIONS: Transesophageal echocardiography is a potentially useful monitor of cardiac filling changes in pediatric patients. PMID- 8342798 TI - Effects of remifentanil, a new short-acting opioid, on cerebral blood flow, brain electrical activity, and intracranial pressure in dogs anesthetized with isoflurane and nitrous oxide. AB - BACKGROUND: A new short-acting opioid, remifentanil, is metabolized by esterase activity in blood and tissue. It is important to know whether remifentanil may decrease the time to recovery of opioid-induced cardiovascular and cerebral effects compared to that of other short-acting agents such as alfentanil. METHODS: Baseline measures were made during 1% end-tidal isoflurane and 50% N2O in oxygen in dogs. Approximately equipotent low- and high-dose remifentanil (0.5 and 1.0 micrograms.kg-1.min-1) or alfentanil (1.6 and 3.2 micrograms.kg-1.min-1) were infused for 30 min each (total infusion time 60 min) followed by a 30-min recovery period. Blood pressure, heart rate, and intracranial pressure were recorded continuously. Electroencephalogram measurements were made using aperiodic analysis, and regional cerebral blood flow using radioactive microspheres. RESULTS: Both remifentanil and alfentanil decreased blood pressure and heart rate 25-30%. Cortex, hippocampus, and caudate blood flow decreased 40 50% during opioid infusion, but flow changes in lower brain regions were modest or absent. The electroencephalogram showed a shift from low-amplitude, high frequency activity during baseline to high-amplitude, low-frequency activity during opioid infusion. During a 30-min recovery period, heart rate, electroencephalogram, and regional cerebral blood flow recovered to baseline levels in remifentanil--but not in alfentanil--treated dogs. Blood pressure and intracranial pressure decreased during opioid infusion and increased above baseline levels during the recovery period in remifentanil-treated dogs. CONCLUSIONS: These results show that the cardiovascular and cerebral effects of remifentanil and alfentanil are similar but that recovery of these parameters occurs sooner following remifentanil. PMID- 8342799 TI - Halothane-oxidant interactions in the ex vivo perfused rabbit lung. Fluid conductance and eicosanoid production. AB - BACKGROUND: The present studies were undertaken to determine the interactions between halothane and oxidative injury with respect to endothelial integrity, as measured by pulmonary capillary filtration coefficient (Kfc), and production of arachidonic acid-derived mediators, in perfused rabbit lungs challenged with the oxidant tert-butyl-hydroperoxide (t-bu-OOH). METHODS: Isolated lungs were prepared from 27 New Zealand white rabbits (2-3 kg) and were perfused with Ca(2+) free Krebs-Henseleit buffer solution. In group A (n = 9), lungs were ventilated with halothane 2.5% in carrier gas (5% CO2 in air); in group B (n = 9), with carrier gas alone; and in group C (n = 9), with carrier gas, but without injury. The lungs in the two injury groups (A and B) received four infusions of t-bu-OOH, 200 microM, over 1 min, directly into the pulmonary artery. The uninjured lungs received four infusions of vehicle (normal saline). Kfc was determined after each t-bu-OOH infusion. Concentrations of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha were measured in samples of effluent perfusate obtained before and 30 s after the end of each infusion of t-bu-OOH. The wet/dry weight ratio of each pair of lungs was determined at the end of each experiment. RESULTS: Kfc progressively increased after each infusion of oxidant in group A when compared with the other two groups. Lung wet/dry ratios were elevated in group A (14.3 +/- 0.7) and group B (13.2 +/- 0.2) compared with group C (12.1 +/- 1.1). TxB2 production in group A (2206 +/- 263 pg.min-1.g-1 dry lung tissue) was greater than in group B (1413 +/- 127) by the final infusion of t-bu-OOH. CONCLUSIONS: Ex vivo perfused rabbit lungs ventilated with halothane exhibited, simultaneously, evidence of greater fluid conductance across the pulmonary capillary bed and production of thromboxane A2 when challenged with oxidant than did lungs ventilated with carrier gas. Both of these effects may be mediated by halothane-related enhancement of intracellular endothelial Ca2+ mobilization stimulated by intrapulmonary infusion of oxidant. PMID- 8342800 TI - A focal cryogenic brain lesion does not reduce the minimum alveolar concentration for halothane in rats. AB - BACKGROUND: A focal cortical cryogenic brain injury has been reported to reduce the brain pentobarbital concentrations needed to prevent movement in response to pain in rats. This occurred despite any apparent behavioral changes in the awake animals. To determine whether this was true with other anesthetics, the authors determined the minimum alveolar concentration (MAC) for halothane in normothermic, normocarbic ventilated Sprague-Dawley rats previously subjected to a freezing injury of the parietal cortex. METHODS: Injury was produced in halothane-anesthetized rats by applying a cold (-70 degrees C), 4-mm-diameter brass rod to the exposed dura for 5 or 15 s. Animals then were studied 3 days after injury, a time when cerebral metabolism in the ipsilateral hemisphere reaches a minimum. Minimum alveolar concentration was determined using a tail clamp stimulus, combined with end-tidal anesthetic sampling. In addition, exploratory activity was measured by the open field test just before MAC determination, and spontaneous nocturnal motility was monitored by an electronic motion sensor during the night before testing. RESULTS: In normal animals subjected only to preparatory surgery, MAC was 1.10 +/- 0.07% (mean +/- SD). Almost identical values were found in rats subjected to 5- and 15-s cryogenic injuries (1.11 +/- 0.07% and 1.08 +/- 0.06%, respectively). There were no intergroup differences in open field test results or in spontaneous nocturnal activity. CONCLUSIONS: These results indicate that a focal cortical brain injury that has no obvious neurologic or behavioral effects in the awake rat does not alter halothane requirements. PMID- 8342802 TI - Severe burn caused by an operating room light. PMID- 8342801 TI - Subanesthetic concentrations of isoflurane suppress learning as defined by the category-example task. AB - BACKGROUND: Previously, we found unconscious (implicit) learning in subjects given subanesthetic, but not anesthetic, concentrations of isoflurane. Other investigators, using different learning tasks, have reported implicit learning at anesthetic concentrations. We investigated whether one of these tasks might provide a more sensitive test of implicit learning. In addition, to determine whether suppression of explicit or implicit learning is dose-dependent, we studied one of the tasks at three subanesthetic concentrations. METHODS: We applied a category-example task at 0.15, 0.28, and 0.4 minimum alveolar concentration (MAC) of isoflurane, and a behavior task only at 0.4 MAC. After anesthesia, we determined whether volunteers more frequently listed an example of a category (e.g., flute as an example of musical instrument) presented during anesthesia and/or demonstrated a behavior (touching ear, chin, or knee) suggested to them at 0.4 MAC. RESULTS: Results from the category task indicated implicit learning only at 0.15 MAC, a concentration that also permitted significant explicit learning. Explicit learning was demonstrated at 0.28 but not at 0.4 MAC (ED50 of 0.20 MAC and ED95 of 0.4 MAC). Results from the behavior task revealed neither implicit nor explicit learning. CONCLUSIONS: The ED50 that suppressed explicit learning in our volunteers equaled that previously reported (0.2 MAC) for implicit learning in volunteers measured using a different task. Combined, these results suggest that less than 0.45 MAC isoflurane suppresses learning in volunteers. PMID- 8342803 TI - Profound hypercarbia late in the course of laparoscopic cholecystectomy: detection by continuous capnometry. PMID- 8342804 TI - Maternal masseter muscle rigidity and neonatal fasciculations after induction for emergency cesarean section. PMID- 8342805 TI - Paradoxical vocal cord motion: an unusual cause of stridor in the recovery room. PMID- 8342806 TI - Cold-induced bronchospasm during coronary artery bypass surgery. PMID- 8342807 TI - Laryngeal mask airway and pulmonary edema. PMID- 8342808 TI - Laryngeal mask airway and pulmonary edema. PMID- 8342809 TI - Laryngeal mask airway and pulmonary edema. PMID- 8342810 TI - Cerebrovascular autoregulation may be the probable mechanism responsible for fentanyl- and sufentanil-induced increases in intracranial pressure in patients with head trauma. PMID- 8342811 TI - Organ perfusion during deliberate hypotension and superimposed hemorrhage. PMID- 8342812 TI - Spinal anesthesia for a former premature infant undergoing upper abdominal surgery. PMID- 8342813 TI - Injection of pancuronium into the masseter muscle for difficult reduction of mandibular dislocation. PMID- 8342814 TI - Ipsilateral shoulder pain following thoracic operations. PMID- 8342815 TI - Ipsilateral shoulder pain following thoracic operations. PMID- 8342816 TI - Henry Ruth, T. Drysdale Buchanan, and history of anesthesia. PMID- 8342817 TI - Henry Ruth and history: his rightful place? PMID- 8342818 TI - Anesthesia studies should include costs. PMID- 8342819 TI - Intrathecal baclofen in tetanus: alternative methods of administration. PMID- 8342821 TI - The safety of sevoflurane in humans. PMID- 8342820 TI - The safety of sevoflurane in humans. PMID- 8342822 TI - Epidural anesthesia and anticoagulation. PMID- 8342823 TI - Epidural anesthesia and anticoagulation. PMID- 8342824 TI - The pupillary light reflex. Effects of anesthetics and hyperthermia. AB - BACKGROUND: The pupillary light reflex often is evaluated in the perianesthetic period to assess drug effects and brainstem function. Mild hypothermia alone or combined with isoflurane does not impair pupillary responses. Although perioperative hyperthermia is less common than hypothermia, abnormal increases in core temperature remain an important thermal disturbance. Accordingly, the pupillary effects of hyperthermia alone and hyperthermia combined with isoflurane and enflurane were evaluated. Additionally, the effects of nitrous oxide on pupillary responses were determined. METHODS: The pupillary light reflex was evaluated in 31 non-surgical volunteers participating in concurrent thermoregulatory studies. Pupillary reflexes were quantified using a portable infrared pupillometer during (1) hyperthermia alone (n = 9), (2) hyperthermia with 0.8% and 1.2% end-tidal isoflurane (n = 8), (3) hyperthermia with 1.7% end tidal enflurane (n = 5), and (4) inhalation of 60% N2O (n = 9). RESULTS: Mild hyperthermia alone (core temperature 38.5 +/- 0.3 degrees C) produced no clinically significant change in the pupillary light reflex. Pupillary responses were decreased markedly with 0.8% isoflurane, 1.2% isoflurane, and 1.7% enflurane when the volunteers were normothermic. Mild hyperthermia combined with isoflurane or enflurane dilated the pupil and increased the amplitude of the light reflex. Sixty-percent nitrous oxide decreased the pupillary reflex only 26 +/- 4%. CONCLUSIONS: Anesthetic-induced inhibition of the pupillary response to light is reversed partially by core hyperthermia. In contrast to enflurane and isoflurane, 60% N2O has little effect on the pupil. PMID- 8342825 TI - The interaction between alcohol and the residual effects of thiopental anesthesia. AB - BACKGROUND: During ambulatory surgery, barbiturates, such as thiopental, may impair psychomotor performance several hours after administration. It was hypothesized that if patients drink alcohol 4 h after thiopental injection, the increase in psychomotor impairment would be greater than that seen after alcohol ingestion alone. METHODS: Twelve healthy men volunteered to participate in a double-blind, placebo-controlled, crossover study with a Latin square design. On each testing day, the subjects received intravenous injections of either 5 mg/kg of 2.5% thiopental or an equal volume of saline for 30 s. Four hours after injection, the subjects consumed a beverage with or without 0.7 g/kg alcohol. Psychomotor performance and mood were assessed at five times: prior to injection, at 1 h and 3 h after injection, and at 1 h and 3 h after consumption of beverage. RESULTS: Both thiopental and alcohol had strong independent effects on the dependent measures in this study. In addition, body sway, one of the nine psychomotor tests used to assess impairment, was greater after thiopental and alcohol than after alcohol alone. Of eleven adjectives used to assess mood, lightheadedness was cited most frequently after a combination of thiopental and alcohol than after each alone. CONCLUSIONS: Based on our tests of performance and mood, an interaction between thiopental and alcohol is evident; in addition, the interaction between both drugs may exert deleterious effects on higher levels of central nervous system integration. PMID- 8342826 TI - Cardiac performance preserved despite thiopental loading. AB - BACKGROUND: Some cerebral artery aneurysms require cardiopulmonary bypass and deep hypothermic circulatory arrest to be clipped safely. During bypass these neurosurgical patients often are given large doses of thiopental in the hope that additional cerebral protection will be provided. However, thiopental loading during bypass has been associated with subsequent cardiac dysfunction in patients with heart disease. This study was undertaken to determine how patients without concomitant heart disease would respond to thiopental loading. METHODS: Twenty four neurosurgical patients with giant cerebral aneurysms and little or no cardiac disease were anesthetized with fentanyl, nitrous oxide, and isoflurane. Thiopental was titrated to achieve electroencephalographic burst-suppression before bypass, and the infusion was continued until after separation. Prebypass hemodynamic and echocardiographic measurements were obtained during a stable baseline and 15 min after thiopental loading began. They were repeated after bypass. RESULTS: Prebypass thiopental loading increased heart rate from 61 +/- 11 to 72 +/- 13 beats/min and decreased stroke volume from 43 +/- 10 to 38 +/- 8 ml.beat-1.m-2, but arterial and filling pressures, vascular resistance, cardiac index, and ejection fraction remained the same. Before bypass, thiopental plasma concentration measured 28 +/- 8 micrograms/ml. Loading continued for 2-3 h until after bypass was terminated, and the overall infusion rate was 18 +/- 5 mg.kg-1.h 1. All patients were easily separated from bypass without inotropic support. Following bypass, vascular resistance was decreased; heart rate, filling pressures, and cardiac index were increased; stroke volume had returned to its baseline; and ejection fraction was unchanged. CONCLUSIONS: It was concluded that if preoperative ventricular function is good, thiopental loading to electroencephalographic burst-suppression causes negligible cardiac impairment and does not impede separation from cardiopulmonary bypass. PMID- 8342827 TI - Pupillary assessment of sensory block level during combined epidural/general anesthesia. AB - BACKGROUND: Currently, no reliable method exists to determine the level of sensory block during combined epidural/general anesthesia. However, the pupil dilates markedly in response to noxious electrical stimulation during general anesthesia. Presumably, sensory block produced by epidural anesthesia decreases or obliterates this autonomic response. Accordingly, we tested the hypothesis that pupillary dilation in response to noxious stimulation would predict the level of sensory block achieved during combined epidural/general anesthesia. METHODS: We studied eight volunteers and ten patients during combined epidural/general anesthesia. The volunteers were given an epidural infusion of 2% 2-chloroprocaine while general anesthesia was maintained with 0.8% isoflurane and 60% N2O. In the patients, an epidural infusion of 0.25% bupivacaine was combined with isoflurane and vecuronium. Noxious electrical stimulation was administered to dermatomal segments in a caudal-to-rostral progression. A twofold increase in pupil size following electrical stimulation was considered the predicted block level in volunteers. In patients, an increase in pupil size exceeding 50% was considered the predicted level. After general anesthesia was discontinued, observers blinded to the pupillary measurements independently determined the actual epidural block level using pain in response to a pinprick as the criterion. RESULTS: The level predicted by pupillary responses was within two dermatomal segments of the actual level in all the volunteers. The predicted and actual block levels were within two segments in eight of the ten patients and never differed by more than four dermatomes. CONCLUSIONS: We conclude that dilation of the pupil in response to electrical stimulation is an accurate test of the sensory block level during combined epidural/general anesthesia. PMID- 8342828 TI - Dose-response pharmacology of intrathecal morphine in human volunteers. AB - BACKGROUND: Intrathecal morphine sulfate (ITMS) administration was introduced into clinical practice in 1979. Inadequate information exists delineating ITMS respiratory effects in the dosage range most frequently employed today. This study evaluated 0.2, 0.4, and 0.6 mg ITMS in male volunteers. METHODS: Twenty healthy, young, adult male volunteers received 0.0, 0.2, 0.4, or 0.6 mg preservative-free ITMS in an isobaric solution administered at the L3-L4 interspace in a double-blind randomized fashion. Respiratory function was assessed by finger pulse oximetry (SpO2), respiratory rate, and arterial blood gas analysis via an indwelling arterial catheter and the slope of the ventilatory response to carbon dioxide (VE/CO2). Analgesia was assessed by the effect of ITMS on moderate pain produced by pressure algometry at the tibia. The need for supplemental oxygen, 2 L/min via nasal cannulae, was determined by the failure of verbal and tactile prompts to maintain subjects' SpO2 > or = 85% on more than two occasions. Heart rate, arterial blood pressure, sedation level, pupil size, and the incidence of adverse effects also were documented. All the above measurements were made before and 30 min after ITMS, hourly for 11 h, and then every 2 h for 12 more h. RESULTS: ITMS produced significant dose-related decreases in SpO2. Mild desaturations (SpO2 > or = 85 and < 90%) occurred in 2 of 5, 3 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. Moderate to severe desaturations (SpO2 < 85%) occurred in 0 of 5, 2 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. The need for supplemental oxygen also was significantly related to ITMS dose, with 0 of 5, 1 of 5, and 4 of 5 subjects requiring oxygen after 0.2, 0.4, and 0.6 mg ITMS, respectively. Nasal oxygen administration consistently alleviated hypoxemia. Increases in arterial carbon dioxide tension (PaCO2) and decreases in pH were significantly related to ITMS dose. Peak mean PaCO2s were 42.4, 44.9, and 50.7 mmHg in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These peaks occurred 6.5-7.5 h after ITMS injection. ITMS produced significant dose-related depression of VE/CO2. Maximum mean depressions of VE/CO2 were to 61%, 63%, and 32% of baseline in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These nadirs occurred 3.5-7.5 h after ITMS injection. Some subjects receiving 0.6 mg ITMS experienced profound (< 20% of baseline) and prolonged (< 50% of baseline for up to 20 h) VE/CO2 depression. Magnitude and duration of analgesia after ITMS were dose-related. Changes in heart rate, systolic blood pressure, and respiratory rate were not significantly related to ITMS dose. Hypoxemia was not related to respiratory rate. Although ITMS produced statistically significant dose-related increases in sedation and decreases in pupil size, these changes were small and did not coincide with hypoxemia. ITMS caused dose-related increases in emesis, but the severity of pruritus and urinary retention was unrelated to dose. CONCLUSION: ITMS produced dose-related analgesia and respiratory depression in nonsurgical healthy, young, adult male volunteers. Respiratory depression was significant after 0.2 or 0.4 mg and profound and prolonged after 0.6 mg. No clinical signs or symptoms, including respiratory rate, reliably indicated hypoxemia. Pulse oximetry reliably detected hypoxemia after ITMS, and supplemental nasal oxygen (2 L/min) effectively corrected this hypoxemia. PMID- 8342829 TI - False-negative results with muscle caffeine halothane contracture testing for malignant hyperthermia. AB - BACKGROUND: During the period 1985-1991, 350 muscle contracture studies have been performed in the authors' laboratory, and during this period, they became aware of an occasional false-negative result. The findings pertaining to the four cases so classified are presented in detail. METHODS: In 1985 the protocol for the muscle strip caffeine halothane testing procedure adopted was that of the European Malignant Hyperthermia Society. RESULTS: Thirty-six percent of the cases tested susceptible for malignant hyperthermia, 15% tested equivocal in that they responded either to halothane or to caffeine singularly, and 49% gave a normal response. In this latter group, the authors believe they identified four false negative results. CONCLUSIONS: This study documents the rarity of false-negative results and substantiates the reliability of caffeine halothane testing as a biologic test in diagnosing the presence of a potentially serious problem. PMID- 8342830 TI - Hemodilution with oxyhemoglobin. Mechanism of oxygen delivery and its superaugmentation with a nitric oxide donor (sodium nitroprusside). AB - BACKGROUND: Hemodilution (HD) with oxyhemoglobin colloid (oxyHb) provides a greater arterial oxygen content (CaO2) than HD with conventional colloids; however, oxygen delivery (DO2) is essentially the same, because, in contrast to conventional HD, cardiac output (CO) is not augmented. This study seeks to elucidate the mechanism that limits CO during oxyHb-HD and to test whether infusion of a nitric oxide (NO) donor would augment DO2, because oxyHb is known to inactivate in vitro endothelial-derived NO. METHODS: Anesthetized dogs were isovolemically hemodiluted with 10% oxyHb, 8% albumin, or 10% methemoglobin (weak NO inactivator) to 20% hematocrit. After HD, sodium nitroprusside (SNP) was titrated intravenously until decreases (> 10 mmHg) in mean aortic pressure (Pao) indicated the presence of exogenous NO. Systemic hemodynamics and regional blood flows (microsphere method) were measured. RESULTS: Albumin-HD and metHb-HD produced typical HD-mediated responses: increased CO (63-65%), slight decreases (13-15%) in DO2, decreases in systemic vascular resistance (SVR) proportional to the decreases (49-52%) in blood viscosity of all three groups, and increased regional blood flows (RBF). Responses to oxyHb-HD were atypical: CO and its determinants were not changed, DO2 decreased (23%) proportional to CaO2, and SVR and most RBF were not changed except for a net redistribution of CO to myocardium and skeletal muscle. In albumin-HD or metHb-HD, SNP (2-5 micrograms.kg-1.min-1) induced comparable decreases in mean Pao (29-37%) and SVR (39-41%); however, CO, RBF, and DO2 were not affected. In oxyHb-HD, exceptionally large doses of SNP (54 +/- 5 micrograms.kg-1.min-1) decreased mean Pao only 19 +/- 1%; however, CO increased 78 +/- 5% and decreases (61 +/- 3%) in SVR were slightly greater than viscosity reductions. Other determinants of CO were not affected. Most RBF increased proportional to CO; there was, however, preferential distribution to myocardium and skeletal muscle. Consequently, the augmented CO, and CaO2 of oxyHb HD, produced large increases in DO2, 77 +/- 5% from HD alone and 43 +/- 3% from prehemodilution values. CONCLUSIONS: This study indicates that the limited CO and DO2 of oxyHb-HD resulted from opposing changes in two determinants of flow, i.e., reduced blood viscosity and increased arterial resistance (vasoconstriction). The vasoconstriction was not evident with metHb-HD and was reversed by the SNP infusion, indicating that oxyHb inactivated in vivo endothelial-derived NO. The ability of the NO donor (SNP) to facilitate large viscosity-mediated increases in DO2 during oxyHb-HD is an important finding that could potentially render oxyHb colloids more useful than conventional colloids, particularly for the individual with a compromised circulation who would benefit from an increased oxygen supply. PMID- 8342832 TI - Tomorrow. PMID- 8342833 TI - Aspirin, the miracle drug: spinally, too? PMID- 8342831 TI - Positive end-expiratory pressure lowers the risk of laser-induced polyvinylchloride tracheal-tube fires. AB - BACKGROUND: The possibility of ignition of polyvinylchloride (PVC) tracheal tubes by a CO2 laser is of concern in patients undergoing CO2 laser surgery of the airway. The authors analyzed the ignition of PVC tracheal tubes by a CO2 laser beam to determine what variables were involved, and then designed a study to determine how they affect the incidence of such fires. METHODS: For the analysis, PVC tracheal tubes were enclosed in a clear plexiglass enclosure and a laser beam was focused on the tubes. The enclosure contained one of three different gas combinations. A high-speed camera photographed the tubes during the analysis and showed that tracheal tube perforation always preceded ignition in all three gas combinations. These results led to the hypothesis that intraluminal gauge pressure (IGP) may be an important variable, because it would affect the flow of O2 across the perforation. This hypothesis was tested by aiming a CO2 laser beam at PVC tracheal tubes and varying IGP in 0.25-cm H2O increments, from 0.25 to 28 cm H2O, while nitrogen or helium containing O2 at 40, 50, or 60% flowed through the tubes. To simulate the clinical effect of IGP on PVC tracheal tube ignition, we used a mechanical lung model connected to an anesthesia breathing circuit with a standing bellows ventilator in which 60% He and 40% O2 flowed through a PVC tracheal tube. Laser beam exposure was started at three different times during the respiratory cycle: at the start of inspiration, at the end of inspiration, or at the end of expiration. Also, for each condition, trials were made at baseline circuit pressure (2.5 cm H2O) and at 5.0 cm H2O by the addition of 2.5 cm H2O positive end-expiratory pressure (PEEP) applied to the circuit. RESULTS: The incidence of tracheal tube ignition decreased as IGP increased. The IGP at which ignition did not occur (which increased as O2 concentration increased) did not differ between N2 and He at 40% O2, but was twice as high with N2 as with He at O2 of 50% and 60%. Fires never occurred when PEEP was added to the system and, when PEEP was not added, always started during the last 2 s of end expiration (when airway pressure is lowest), regardless of when the laser beam was activated. CONCLUSIONS: It is recommended that, in addition to other safety practices, PEEP be added to the breathing circuit during CO2 laser operations on the airway in which PVC tracheal tubes or laser-resistant tracheal tubes with PVC components are used. PMID- 8342834 TI - The effects of preinduction warming on temperature and blood pressure during propofol/nitrous oxide anesthesia. AB - BACKGROUND: Core temperature decreases rapidly after induction of anesthesia, largely because heat is redistributed to peripheral tissues. The hypothesis that warming peripheral tissues before induction of general anesthesia (prewarming) minimizes hypothermia was tested. Because circulating blood volume may be greater during exposure to heat compared to cold, the hypothesis that prewarming decreases the amount of hypotension associated with induction of anesthesia was tested also. Finally, the hypothesis that the difference between direct radial arterial blood pressure and blood pressure measured oscillometrically at the brachial artery depends on thermoregulatory and anesthetic conditions was tested. METHODS: Each of six volunteers underwent general anesthesia (propofol and nitrous oxide) twice on the same day. Each anesthetic lasted 1 h and was preceded by either 2 h of active warming with forced air or 2 h of passive cooling by exposure to a typical operating room environment. After induction of each anesthetic, volunteers were fully exposed to the ambient environment. Volunteers recovered for 2 h before starting the second preinduction treatment. RESULTS: Initial tympanic membrane temperatures were similar before each preinduction treatment: 36.7 +/- 0.4 degrees C when volunteers were not warmed and 36.7 +/- 0.6 degrees C when volunteers were warmed. Tympanic membrane temperature did not change during the preinduction period without warming but increased slightly (delta T = 0.4 +/- 0.2 degree C) during warming. After induction of anesthesia, core temperatures decreased to 36.1 +/- 0.4 degree C over 1 h when volunteers were prewarmed but decreased to 34.9 +/- 0.4 degrees C when they were not. Radial arterial systolic, diastolic, and mean blood pressures were lower before induction of anesthesia when volunteers were warmed compared to when no warming was given. Oscillometric diastolic and mean pressures also were lower during prewarming; however, oscillometric systolic pressure did not differ significantly. Prewarming did not result in less hypotension after induction. Without warming, the difference (radial arterial minus oscillometric) in systolic blood pressure measurements was approximately 17 mmHg. Warming was associated with a reversal of the systolic pressure difference to approximately -6 mmHg. After induction of anesthesia, the differences in systolic and mean pressure measurements became more negative with respect to the preinduction values regardless of preinduction warming treatment. CONCLUSIONS: These data confirm our hypothesis that redistribution hypothermia can be minimized by preinduction warming of peripheral tissues. Prewarming decreases blood pressure but does not prevent subsequent hypotension after induction. The difference between radical arterial blood pressure and oscillometric blood pressure depends on thermoregulatory vasomotor changes but also may be influenced by vasodilation associated with administration of propofol and nitrous oxide. PMID- 8342835 TI - Comparison of effects of sevoflurane/nitrous oxide and enflurane/nitrous oxide on myocardial contractility in humans. Load-independent and noninvasive assessment with transesophageal echocardiography. AB - BACKGROUND: Few studies have been reported on the direct depressive effects of sevoflurane on myocardial contractility in humans. Direct assessment of contractile state is possible by examining the slope of left ventricular end systolic wall stress (LVESWS) versus velocity of circumferential fiber shortening with heart rate corrected (Vcfc) relationship with echocardiography. Using this contractile index, the effects of sevoflurane/nitrous oxide were compared with that of enflurane/nitrous oxide on myocardia contractility in humans. METHODS: Twenty-eight subjects were studied during either sevoflurane/nitrous oxide or enflurane/nitrous oxide anesthesia. Systolic, diastolic, and mean arterial blood pressure, heart rate, and transesophageal echocardiographic data were determined at 0.9 MAC and 1.35 MAC of sevoflurane or enflurane, both with 60% N2O, and at 1.6 MAC of sevoflurane with 60% N2O. Furthermore, another 28 awake subjects were studied with transthoracic echocardiography to examine the contractile state at awake state, and echocardiograms, heart rate, and arterial blood pressure were recorded. RESULTS: Heart rate did not changed significantly in either group. Enflurane/nitrous oxide produced significantly greater decrease in arterial blood pressure than did sevoflurane/nitrous oxide. The Vcfc at each anesthetic dose in both anesthetic groups was significantly less than that in the awake subjects group. Sevoflurane/nitrous oxide produced no significant change in Vcfc at 1.5 MAC, whereas enflurane/nitrous oxide caused significant dose-related decrease in Vcfc. Vcfc produced by sevoflurane/nitrous oxide was significantly greater than that produced by enflurane/nitrous oxide. There was no significant difference in LVESWS (index of afterload) between the groups. With respect to the LVESWS-Vcfc relationship, myocardial contractility was significantly depressed in both the sevoflurane and the enflurane groups compared to the awake subjects group. However, myocardial contractility produced by enflurane/nitrous oxide was significantly less than that by sevoflurane/nitrous oxide at equiMAC concentration. CONCLUSIONS: The results of the present study suggest that sevoflurane has fewer depressant effects on cardiac function than does enflurane. PMID- 8342836 TI - The esophageal detector device. Does it work? AB - BACKGROUND: The esophageal detector device (EDD) is a diagnostic tool for confirmation of tracheal intubation. Capnography is the accepted standard for such confirmation. The purpose of this investigation was to determine whether results using the EDD and capnography agree. METHODS: Five hundred patients were divided into three separate studies. In study 1, with 300 consecutive patients, tracheal intubation was performed and tested with the EDD followed by capnography. In study 2, 100 patients had the esophagus intentionally intubated, and confirmation was tested similarly. The tube was then removed and the trachea intubated, and testing followed. Study 3 involved 100 patients and used a double blind, randomized design. The tube was intentionally inserted into either the esophagus (n = 5) or trachea (n = 49), and testing followed. RESULTS: In study 1, the compressed EDD bulb reinflated 270 times and always agreed with capnography; in 20 of the 270 subjects (7%) bulb reinflation was delayed, taking from 5-30 s. In 30 instances, the bulb remained compressed, and there was no capnogram indicating esophageal intubation. In study 2, regardless of esophageal or tracheal intubation, agreement between EDD and capnogram was 100%. In study 3, the agreement between the two detecting instruments was 100%, but reinflation of the EDD bulb was delayed in 4% of tracheal intubations. In the 500 patients studied, results from the EDD and capnogram always agreed, but in 6% of all tracheal intubations, the EDD bulb inflated slowly. Of 181 esophageal intubations, the results from the EDD and capnogram always agreed, i.e., there was no reinflation or capnogram. The sensitivity, specificity, and predictive value for the EDD in all of these studies was 100%. CONCLUSIONS: The EDD is a valuable diagnostic technique for confirming tracheal intubation. Results using EDD agree with results using capnography; in 6% of instances there is a slow reinflation; and where there is no capnography, such as on hospital wards, EDD may be a useful diagnostic tool. PMID- 8342837 TI - The effect of sensor malpositioning on pulse oximeter accuracy during hypoxemia. AB - BACKGROUND: Previous studies have shown that pulse oximeters whose sensors are positioned improperly may yield erroneously low saturation (SpO2) values on normoxemic subjects. The behavior of oximeters with malpositioned sensors during hypoxemia has not been studied. The current study is aimed at determining the behavior of several different pulse oximeters over a wide range of arterial oxygen saturation (SaO2). METHODS: In each of 12 healthy volunteers, a radial artery cannula was inserted, and eight different pulse oximeters, five of which had malpositioned sensors, were applied. Subjects breathed controlled mixtures of nitrogen and oxygen to slowly vary their SaO2 from 100% to 70%. Arterial blood samples were analyzed and pulse oximeter data were recorded at five stable SaO2 values for each subject. RESULTS: The oximeters with malpositioned sensors vary greatly in their behavior, depending on both the actual SaO2 and the manufacturer and model. One oximeter underestimated saturation at all SaO2 values, while three others underestimated at high SaO2 and overestimated at low SaO2. Linear regression analysis shows a decrease in the slope of SpO2 versus SaO2 in most cases, indicating a loss of sensitivity to SaO2 changes. Between-subject variation in response curves was significant. CONCLUSIONS: The calibration curves of the pulse oximeters studied were changed greatly by sensor malpositioning. At low SaO2 values, these changes could cause the oximeter to indicate that a patient was only mildly hypoxemic when, in fact, hypoxemia was profound. It is recommended that sensor position be checked frequently and that inaccessible sensor locations be avoided whenever possible. PMID- 8342838 TI - Perioperative platelet reactivity and the effects of clonidine. AB - BACKGROUND: Increased postoperative platelet reactivity may contribute to arterial thrombotic complications following surgery. alpha 2 Agonists, which are being used increasingly to blunt the stress response of surgery, increase platelet aggregation in vitro. We compared perioperative changes in platelet reactivity in 21 patients receiving either clonidine or placebo. METHODS: Patients undergoing major abdominal surgery were randomized to receive oral and transdermal clonidine (n = 11) or placebo (n = 10). All patients received similar perioperative management, including preoperative sedation, general anesthesia without neuraxial opioids, or local anesthetics and postoperative patient controlled intravenous morphine. Blood was obtained for measurement of clonidine level, fibrinogen concentration, platelet count, and platelet reactivity (impedance aggregometry and dense granule release) before induction and 24, 48, and 72 h postoperatively. RESULTS: Thirteen of the 21 patients had biopsy-proven cancer at surgery, 5 of 11 received clonidine and 8 of 10 received placebo (NS). Clonidine levels were therapeutic (1-2 ng/ml) throughout the study period. Clonidine administration had no effect on platelet count or platelet reactivity. Therefore, the groups were combined for further analysis. In this group (n = 21), compared to preoperative values, fibrinogen levels rose maximally (36%) at 72 h postoperatively and platelet counts decreased 22% at 48 h. Platelet reactivity (aggregation and degranulation) to collagen, adenosine diphosphate, arachidonic acid, and ristocetin, increased at 24, 48, and 72 h postoperatively. Thrombin induced (supramaximal stimulus) dense granule release did not change from preoperative values. CONCLUSIONS: These data indicate that major abdominal surgery causes increased platelet reactivity postoperatively but does not effect maximal degranulation. This increased platelet reactivity occurs within 48 h of surgery, coinciding with the peak incidence of postoperative arterial thrombotic complications. Clonidine administration has no effect on surgically induced changes in platelet reactivity. In this surgical patient population, the use of clonidine should not increase the risk of platelet-induced perioperative arterial thrombosis. PMID- 8342839 TI - Clonidine pretreatment reduces the systemic toxicity of intravenous bupivacaine in rats. AB - BACKGROUND: Clonidine prolongs the duration of sensory and motor block induced by bupivacaine, and this association, in constant infusion by the epidural route, is used for postoperative analgesia. After a near-fatal intravenous bolus of bupivacaine in dogs, clonidine improves ventricular electrophysiologic parameters, but probably worsens bupivacaine-induced bradycardia and depression of the myocardial contractility. The current study, using a rodent animal model, evaluated the influence of clonidine pretreatment on the systemic toxic effects of bupivacaine overdose induced by a constant intravenous infusion. METHODS: Twenty Wistar male rats were anesthetized with thiopental, and controlled ventilation was started with an equal mixture of O2 and N2O. Electrocardiogram (ECG), electroencephalogram (EEG), and invasive arterial blood pressure were continuously recorded. Clonidine (5 micrograms/kg) or saline was injected intravenously in a randomized fashion. After 15 min, an intravenous infusion of bupivacaine was started at 2 mg.kg-1 x min-1. The time of occurrence of the bupivacaine-induced toxic events was recorded and the doses were calculated. Ten (five in each group) additional rats, pretreated according to the same protocol, were killed at the time of the first dysrhythmia, for blood sampling and plasma bupivacaine concentration measurement. RESULTS: Clonidine reduced heart rate and arterial blood pressure before bupivacaine infusion (P < 0.05). The threshold doses at the first QRS modification (11.3 +/- 5.6 vs. 2.1 +/- 0.9 mg/kg) and the first dysrhythmia (40.6 +/- 15.3 vs. 8.48 +/- 3.7 mg/kg), the increase in EEG total spectral power (33.3 +/- 21.9 vs. 8.2 +/- 5.1 mg/kg), the 25 and 50% reduction in baseline mean arterial pressure and heart rate, the isoelectric EEG (58.6 +/- 14 vs. 22 +/- 6.6 mg/kg), and the final systole (99 +/- 16 vs. 51.8 +/- 14.5 mg/kg) were significantly greater in the clonidine group than in the saline group (P < 0.01). The time between the first dysrhythmia and 50% reduction of baseline mean arterial blood pressure was not different between the groups. In the additional series, the first dysrhythmia occurred later (10.9 +/- 4.5 vs. 3.2 +/- 1.0 min, P < 0.01) and plasma bupivacaine levels were greater (18.7 +/- 8.0 vs. 7.8 +/- 3.2 micrograms/ml, P < 0.01) in the clonidine group than in the saline group. CONCLUSIONS: In this model, clonidine given prophylactically delays the toxic manifestations of bupivacaine overdose and does not accentuate the subsequent hypotension. PMID- 8342840 TI - Effects of halothane, propofol, and thiopental on peripheral airway reactivity. AB - BACKGROUND: General anesthetics modify airway responsiveness by several mechanisms, including direct effects on airway smooth muscle and reductions in neural reflex activity. Halothane has been shown to reduce responsiveness through both of these mechanisms. The airway effects of barbiturates are controversial, and the effects of propofol are unknown. METHODS: To compare the direct effects of halothane, thiopental, and propofol in vivo, canine peripheral airways were constricted with two stimuli, histamine and hypocapnia, which are thought to directly contract smooth muscle. The authors then investigated the role of ATP sensitive potassium (KATP) channels as a mechanism for attenuating these responses. Basenji-Greyhound (BG) dogs were anesthetized with either halothane (1.5 MAC), thiopental (7.5 mg.kg-1 x min-1 intravenously) plus fentanyl (25 micrograms intravenously every 20-30 min), or propofol (0.6 mg.kg-1 x min-1 intravenously). A wedged bronchoscope technique was used to measure peripheral airway resistance (RP). After a stable baseline was obtained, dose-response curves to histamine (50, 100, or 200 micrograms intravenous bolus) or hypocapnia (0% CO2 for 2 min with 100, 200, or 400 ml/min collateral flow) were constructed. On separate occasions, the same sublobar segments were pretreated with glibenclamide (2 mg/ml aerosol), a KATP channel blocker, and dose-response curves to hypocapnia were repeated. RESULTS: Dose-response curves to histamine were similar during all three anesthetics. Halothane decreased airway responsiveness to hypocapnia, compared with either thiopental or propofol (P < 0.05). Pretreatment with glibenclamide abolished the effect of halothane on hypocapnia induced airway constriction. CONCLUSIONS: These results indicate that propofol afforded no benefit over thiopental or halothane in reducing peripheral airway responsiveness. Furthermore, the beneficial effects of halothane in reducing responsiveness to hypocapnia appear to be mediated by the opening of KATP channels. PMID- 8342841 TI - Effects of pentobarbital and isoflurane on regional cerebral oxygen extraction and consumption with middle cerebral artery occlusion in rats. AB - BACKGROUND: When compared with barbiturates, isoflurane may lack protective effects during focal cerebral ischemia. The reason for this difference is not clear. In this study, regional cerebral blood flow (rCBF), arterial and venous O2 saturation, and O2 extraction were compared in the ischemic cortex and in the nonischemic brain regions of rats anesthetized with isoflurane or pentobarbital using a microspectrophotometric technique that directly measures the O2 saturation of blood in the small arteries and veins. METHODS: Twenty-eight rats were anesthetized with 1.4% isoflurane or 50 mg/kg pentobarbital. One hour after a middle cerebral artery (MCA) occlusion, rCBF was measured in the ischemic cortex and in the nonischemic brain regions using 14C-iodoantipyrine in one-half of each group of animals. Regional arterial and venous O2 saturation were determined using microspectrophotometry in the other one-half of each group. RESULTS: The rCBF of the ischemic cortex (IC) and the non-ischemic contralateral cortex (CC) of the isoflurane group were significantly higher than those of the pentobarbital group. The venous O2 saturation was significantly less, and the O2 extraction was significantly higher, in the IC than in the nonischemic regions in both groups of animals (pentobarbital group, IC 10.5 +/- 1.1 ml O2.100 ml blood 1, CC 6.3 +/- 0.7; isoflurane group, IC 10.8 +/- 0.6, CC 5.9 +/- 0.2). There was no significant difference between the two groups. CONCLUSIONS: Because the rCBF was less and the O2 extraction was similar, O2 consumption in the focal ischemic area of the brain during pentobarbital anesthesia must have been less than that during isoflurane anesthesia. PMID- 8342842 TI - Mechanism of the direct, negative inotropic effect of ketamine in isolated ferret and frog ventricular myocardium. AB - BACKGROUND: Ketamine exerts both an indirect, positive inotropic effect and a direct, negative inotropic effect in isolated ferret ventricular myocardium. This negative inotropic effect becomes apparent after inactivation of the sympathetic neuroeffector junction. The aim of this study was to investigate the mechanisms of ketamine's intrinsic negative inotropic effect. METHODS: The authors analyzed the effects of ketamine after beta-adrenoceptor blockade on variables of contractility and relaxation, and on the free intracellular Ca++ transient detected with the Ca(++)-regulated photoprotein aequorin. Ketamine's effects were also evaluated in a preparation in which the sarcoplasmic reticulum (SR) function was impaired by ryanodine, and in frog ventricular myocardium in which the SR is poorly developed. RESULTS: Ketamine at concentrations > or = 3.3 x 10(-5) M decreased contractility and the amplitude of the intracellular Ca++ transient. After inactivation of sarcoplasmic reticulum Ca++ release with 10(-6) M ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca++ influx, ketamine caused a decrease in contractility and in the amplitude of the intracellular Ca++ transient, and ketamine's relative negative inotropic effect was not different from that in control muscles not exposed to ryanodine. Furthermore, > or = 10(-4) M ketamine decreased contractility in frog ventricular myocardium, a species that is almost entirely dependent on transsarcolemmal Ca++ influx for its myofibrillar activation. CONCLUSIONS: These findings indicate that the direct negative inotropic effect of ketamine results from a decrease in intracellular Ca++ availability with no changes in myofibrillar Ca++ sensitivity. At least part of ketamine's action is caused by inhibition of transsarcolemmal Ca++ influx. PMID- 8342843 TI - Prolonged regional nerve blockade by controlled release of local anesthetic from a biodegradable polymer matrix. AB - BACKGROUND: Prolonged nerve blockade is potentially useful in the management of many acute and chronic pain problems. Aside from infusions via an indwelling catheter, most currently available nondestructive techniques for prolonging local anesthetic action cannot provide more than 1-2 days of blockade. Bioerodible polymer matrixes have been used to deliver a variety of drugs in patients and animals for periods lasting weeks to years. Previously, dibucaine and bupivacaine were incorporated into copolymers of 1,3 bis(p-carboxyphenoxy) propane-sebacic acid anhydride (1:4), and demonstrated sustained release in vitro following incubation of the drug-polymer matrixes in phosphate-buffered solution (pH 7.4, 37 degrees C). METHODS: In the present study, cylindrical pellets made from polymer matrixes incorporated with bupivacaine-HCl were implanted surgically along the sciatic nerves of rats. Neural block was assessed by direct observation of motor skills and by leg-withdrawal latency to a hot surface. Biochemical and histologic examinations were performed 2 weeks after implantation. RESULTS: Sensory and motor blockade was produced for periods ranging from 2 to 6 days. Contralateral control legs receiving polymer implants without drug showed no block. Blockade was reversible, and animals appeared to recover sensory and motor function normally. Biochemical indexes of nerve and muscle function were indistinguishable from contralateral controls. CONCLUSIONS: This biodegradable polymer system provides a promising new alternative for the delivery of local anesthetics to peripheral nerves to produce prolonged blockade for the management of acute and chronic pain. PMID- 8342844 TI - The effect of a platelet activating factor antagonist (BN 52021) on neurologic outcome and histopathology in a canine model of complete cerebral ischemia. AB - BACKGROUND: Research has demonstrated that platelet activating factor may modulate, in part, the severity of postischemic neurologic injury. The proposed mechanism involves a platelet activating factor-mediated release of cerebral cellular lipids and free fatty acids, resulting in increased cerebral edema and cell injury. The present study tested the hypothesis that a specific platelet activating factor antagonist, BN 52021, would improve neurologic outcome after 12 min of complete global cerebral ischemia in a canine model. METHODS: Using an established canine model of complete cerebral ischemia, dogs were assigned randomly to receive, in a blinded fashion, either 20 mg/kg BN 52021 intravenously (N = 8) or placebo (N = 7) 5 min before cerebral ischemia. After cerebral ischemia and recovery, neurologic assessment was performed by a blinded observer for 72 h. Immediately thereafter, the brains were harvested and later were evaluated histologically by a neuropathologist blinded to the treatment groups. RESULTS: Dogs were well matched for systemic physiologic variables during all portions of the study. One placebo-treated dog and one BN 52021-treated dog were not included in the statistical analysis because of failure to meet preestablished protocol criteria. BN 52021, when compared to placebo, affected neither neurologic functional recovery nor overall histopathology scores. Regional histopathology was improved in BN 52021-treated dogs in only 1 of 18 brain regions studied (i.e., the parietal cortex). When both treatment groups were combined, there was a significant correlation between neurologic function rank and histopathology rank. CONCLUSIONS: The present data demonstrate that the platelet activating factor antagonist BN 52021, at a dose of 20 mg/kg intravenously given 5 min before cerebral ischemia, did not protect the brain from injury in this canine model of complete global ischemia. PMID- 8342845 TI - Evaluation of central spinal cord injury pain with diagnostic spinal anesthesia. PMID- 8342846 TI - Indigo carmine-induced severe hypotension in patients undergoing radical prostatectomy. PMID- 8342847 TI - Is it time to correct the dermatome chart of the anterior scrotal region? PMID- 8342848 TI - Diagnosis of myocardial injury by real-time recording of ST segments of the electrocardiogram in a patient receiving general anesthesia for electroconvulsive therapy. PMID- 8342849 TI - Intraarterial vasodilator administration to restore pulse oximeter function. PMID- 8342850 TI - Pacemaker interactions with transcutaneous cardiac pacing. PMID- 8342851 TI - Electrocardiographic and hemodynamic changes associated with unintentional intravascular injection of bupivacaine with epinephrine in infants. PMID- 8342852 TI - A simple technique for placement of the Univent bronchial blocker. PMID- 8342853 TI - Needleless intravenous administration system. PMID- 8342854 TI - Barrier flaps for continuous caudal anesthesia in pediatric patients. PMID- 8342855 TI - Succinylcholine and Duchenne muscular dystrophy. PMID- 8342856 TI - Euthanasia and anesthesiologists. PMID- 8342857 TI - Euthanasia: wisdom or folly? PMID- 8342859 TI - Pitfalls in performing meta-analysis: I. PMID- 8342858 TI - Euthanasia in the intensive care unit. PMID- 8342860 TI - Anesthetic care and management of patients who are deaf and mute. PMID- 8342861 TI - Believe your monitors. PMID- 8342862 TI - Periarterial lidocaine/hydralazine aids arterial catheter insertion in patients with preeclampsia. PMID- 8342863 TI - Research and the laryngeal mask airway. PMID- 8342864 TI - Defining the difficult airway. PMID- 8342865 TI - Severity of illness classification for infection control departments: a study in nosocomial pneumonia. AB - BACKGROUND: A subjective severity of illness classification was evaluated in a study of nosocomial pneumonia. This is a 5-category system based on the determination of the control of underlying illness and the risk of death during current hospital admission. METHODS: A case-control study was performed with 128 cases of nosocomial pneumonia and 252 control patients. An additional 60 case and 90 control patients were used to compare this classification with APACHE II scoring in intensive care unit patients. RESULTS: In univariate analysis, the severity illness classification was significantly associated with nosocomial pneumonia risk (p < 0.01). APACHE II adequately predicted mortality rate but was not statistically significantly associated with nosocomial pneumonia risk among intensive care unit patients. In logistic regression analysis, the severity of illness classification, surgery, age, nasogastric tube placement, and histamine blockers each showed significant independent association with nosocomial pneumonia. CONCLUSIONS: The role of the severity of illness classification for risk stratification in nosocomial pneumonia is valid. Its roles in the evaluation of surgical wound infection, nosocomial bacteremia, and quality of care remain to be determined in subsequent studies. PMID- 8342867 TI - Infection control and bone marrow transplantation. AB - BACKGROUND: Bone marrow transplantation for the treatment of malignancies is on the increase. Unfortunately, there are no well-validated infection control guidelines for this highly susceptible population. METHODS: Literature was reviewed concerning infection risks and interventions to decrease risks for bone marrow transplant recipients. RESULTS: Definitive information was generally lacking. However, basic "common sense" infection control recommendations for bone marrow transplantation were made in the following areas: air ventilation systems, design issues, environmental services, patient care issues, barrier precautions, nosocomial surveillance, and discharge planning. Recommendations must be tailored to each facility or setting. CONCLUSION: We conclude that validation of many of these recommendations is necessary to provide optimum care for bone marrow transplant recipients. PMID- 8342866 TI - Measles susceptibility and immunization: experiences in a forensic psychiatric hospital. AB - BACKGROUND: In response to a measles outbreak in the community, a measles immunization program was developed at our hospital for forensic psychiatric patients. METHODS: Measles antibody screening of all employees and patients by means of an enzyme-linked immunosorbent assay was followed by vaccination of susceptible persons. RESULTS: Serum samples from 813 employees and 868 patients during a 6-month period were analyzed. The susceptibility rate was 16.15% for employees and 13.60% for patients born in or after 1957. It was 4.67% for employees and 5.40% for patients born before 1957. The overall rate was 7.38% for employees and 8.53% for patients. A rate of 5% is known to be sufficient for transmission in institutions. Vaccine was given to 84.51% of susceptible patients. Vaccine failure occurred in 8.33%. Residual susceptibility rate was 1.84%. CONCLUSIONS: Cost analysis showed that screening of all individuals and immunization of susceptible persons was the most cost-effective method for measles control in our institutional setting. PMID- 8342868 TI - A Flavobacterium meningosepticum outbreak among intensive care patients. AB - A Flavobacterium meningosepticum outbreak, involving 12 infected and 47 colonized intensive care patients during the months of February through July 1990, was investigated. F. meningosepticum was isolated from tap water and ice, but these environmental strains eventually proved to be distinct from those colonizing patients. A review of newly colonized patients' charts revealed that a common factor among the patients was daily changes of ventilator tubing pasteurized in the hospital's central sterile department. More than 90% of patients in the outbreak had been on ventilators that used the pasteurized tubing. An investigation of the pasteurization process found that two pasteurizer tanks had been operating at suboptimal temperatures (< 62 degrees C). Cultures of water from the tanks and droplets of water found in the pasteurized tubing grew species of Acinetobacter, Moraxella, and Pseudomonas but did not grow F. meningosepticum. After deficiencies in the pasteurization process were corrected, the outbreak terminated. Despite the failure to culture F. meningosepticum, an analysis of gram-negative bacillary isolates showed that the deficiency in the pasteurization process was a major contributor to colonization of ventilated patients by bacteria ubiquitous in tap water. PMID- 8342869 TI - Infection control in home care agencies. AB - BACKGROUND: The purpose of this study was to describe the characteristics of home care agencies, including the nature of care provided and the presence of infection control standards and education. METHODS: Study design was cross sectional and descriptive; the survey of home health agencies included questions about agency type, nature of care delivered, and infection control policies and educational programs. The sample included all directors of home care agencies in northern California. RESULTS: The response rate was 33.5%. Agency directors reported that 15.3% of their clients required high-technology nursing care; in response to a list of invasive procedures generally considered high in infection risk, more than 90% cared for urinary drainage devices, some categories of wound care, and intravenous management. Of those performing high-risk procedures, more than 75% had policies covering the procedures. Nearly all (87.7% to 100%) had policies on universal precautions, handwashing, handling of needles and sharps, and the cleaning and disinfection of equipment; however, nearly a quarter (24.6%) had no education program regarding the handling of contaminated equipment. CONCLUSIONS: Among agencies responding to this survey, care that is considered high risk for infection is delivered and the agencies for the most part have infection control policies and educational programs. Research is needed to define more clearly infection control efforts in home health care. More work is needed to adapt the knowledge of infection control in hospitals to the home setting. PMID- 8342870 TI - The numbers game: sample-size determination. AB - Sample-size determination is a crucial component of study design. Estimates of sample size are influenced by the amount of change that must occur between study groups and the degree of risk that the investigator is willing to accept in evaluating the null hypothesis. A complete understanding of the impact of sample size on the interpretation of study data is therefore a prerequisite for quality, innovative, valid research. PMID- 8342871 TI - Use of the total quality process in an infection control program: a surprising customer-needs assessment. AB - The University of Michigan Hospitals began a quality management and improvement process in 1987 as the framework for all of its quality-related efforts and activities. The Infection Control Services department used total quality techniques to develop its mission statement, identify customers, identify customer requirements, and develop quality improvement objectives to meet the requirements. A service evaluation of customers resulted in specific improvement activities. An unexpected result of this evaluation was the difference noted between the Infection Control Services staff members' perception of customer requirements and these customers' actual needs. ICPs should use the continuous quality improvement tools and techniques to enhance their activities within their institutions, to better meet their customer needs, and to make sure that they are complementing their institution's mission. PMID- 8342872 TI - Prospective, randomized trial of barrier isolation versus universal precautions during medical intensive care. PMID- 8342873 TI - Draft APIC guideline for infection prevention and control in flexible endoscopy. Association for Practitioners in Infection Control, Inc. PMID- 8342875 TI - Analysis of familial and individual risk factors among patients with ischemic vascular dementia and Alzheimer's disease. AB - The purpose of this study was to determine relative contributions of first-degree familial and individual risk factors to clinical manifestations of two major age related dementias. The authors interviewed 183 patients with dementia of the Alzheimer's type (DAT) and 137 patients with ischemic vascular dementia (IVD) together with family members and caregivers. Information was also obtained from medical records and collateral sources as required. Risk factor data within a predictive model for differentiating the two dementias were evaluated. There was a greater incidence of family history of degenerative and dementing neurologic disorders in DAT than in IVD. Both groups were equivalent for family histories of cerebrovascular disease. Despite familial equivalence, patients with IVD had a greater individual incidence of risk factors for cerebrovascular disease. Analysis by gender revealed three observations. Among DAT patients, family history for degenerative and dementing neurologic disorders proved to be significantly greater among women than among men. This risk factor did not, however, predict individual diagnoses for DAT. Women with IVD were more likely to have a family history of cancer than men. Multiple regression analyses revealed that reduced educational levels in women predicted greater liability for IVD than for DAT. Hypertension, heart disease, and diabetes mellitus were all risk factors for IVD, but not for DAT. CONCLUSIONS: Individual and familial historical data provide useful information concerning identification, pathogenesis, prevention, and treatments for vascular dementia but little predictive information for identifying patients with Alzheimer's disease. PMID- 8342874 TI - Features of coronary artery lesions related to left ventricular aneurysm formation in anterior myocardial infarction. AB - To determine the factors of left ventricular aneurysm formation in acute myocardial infarction, the authors studied the distribution of coronary artery lesions and the left ventricular wall motion of 43 patients with anterior myocardial infarction. Of 15 patients with aneurysm, 9 (60%) showed a single vessel disease with severe stenosis of the proximal left anterior descending artery. Of 9 patients with triple-vessel disease, 8 (89%) had no aneurysm. In patients with the aneurysm, the Gensini score of the culprit lesion was significantly higher (p < 0.05) and the score except for the culprit lesion was less (chi 2 = 5.7, p < 0.05). In 23 patients with single-vessel disease, the collateral score was significantly less (p < 0.05) in patients with the aneurysm. The systolic wall motion on the ventriculogram appeared more impaired in the anterior infarct area but well maintained in the posterior noninfarct area in patients with the aneurysm. In conclusion, the important factors of left ventricular aneurysm formation were as follows: (1) A culprit lesion of the myocardial infarction was severe, but other coronary artery lesions were mild. (2) Collateral vessels were poor. (3) The left ventricular wall motion of the infarct area was impaired, but that of the noninfarct area was relatively good. PMID- 8342876 TI - Carotid ultrasonographic findings in intracranial internal carotid artery occlusion. AB - Five cases of unilateral intracranial internal carotid artery (ICA) occlusion received both carotid angiographic and ultrasonographic studies. The Doppler examination showed that the resistive index (RI) of the common carotid artery (CCA) and ICA was higher but the peak systolic velocity was lower on the diseased side as compared with the normal side. Absence of the diastolic phase was found in the CCA flow in 2 cases and in the ICA flow in 3 cases on the diseased side. The mean CCA flow volume on the diseased side (271 +/- 82 mL/min) was half or less than that on the normal side (680 +/- 86 mL/min) (P < 0.01). The flow volume of the diseased ICA (49 +/- 20 mL/min) was markedly lower than that of the normal side (344 +/- 49 mL/min) (P < 0.01) and was also less than that of the ipsilateral external carotid artery (ECA) (129 +/- 43 mL/min). The Doppler ophthalmic artery flow all showed a forward direction. The authors propose that the following extracranial carotid ultrasonographic findings may be helpful in the prediction of intracranial carotid artery occlusion: (1) diminished frequencies, increased RI, and a more than 50% reduction of flow volume in the CCA as compared with the opposite side; (2) diminished frequencies to loss of the diastolic phase, a more than 50% reduction of the flow volume, and reversed ICA/ECA flow volume in the ICA as compared with the opposite side; and (3) a forward Doppler ophthalmic artery flow. PMID- 8342877 TI - Simultaneous recording of blood volume shifts in different vascular beds in man by a versatile scintigraphic method. AB - A device was developed to record the blood volume changes occurring in the lung and calf during postural changes, physical exercise, and the Valsalva maneuver in man. The changes in regional counting rates from the right middle lung and the calf mirrored the well-known changes in venous return that are expected to occur in response to the above-mentioned external stimuli. Thus a sustained decrease in lung blood volume was noted on assumption of the erect posture as well as during the forced expiration of the Valsalva maneuver. In addition a rapid increase and a sharp decrease in lung blood volume took place at the very onset and at the very end of walking, respectively. The calf blood volume declined immediately at the onset of walking, increased slightly in the ensuing two minutes, and returned to baseline quickly at the termination of walking. The authors' method enables real-time equilibrium blood pool scintigraphy to be recorded continuously and simultaneously from different districts over sustained periods of time irrespective of the posture and the physical activity performed by the patient. Their method might improve knowledge of the systemic circulatory responses to selective physiologic and therapeutic interventions in health and disease. PMID- 8342878 TI - Hemorheologic approach in the treatment of diabetic foot ulcers. AB - Pentoxifylline, a new trisubstituted methylxanthine derivative, is the most well known of a new group of hemorheologic agents. It has been shown to improve hemorheologic abnormalities associated with diabetes and atherosclerosis. The authors examined the role of pentoxifylline in the treatment of diabetic foot ulcers. Forty diabetic patients with foot ulcerations were included in the study, 20 of whom received conventional therapy and 20 received pentoxifylline (400 mg three times a day) in addition. Healing of ulcers after eight weeks of treatment was significantly higher in those on pentoxifylline, and the patients needed less mutilating surgery. Administration of pentoxifylline in addition to conventional therapy was significantly superior in the management of diabetic foot ulcers. PMID- 8342879 TI - Effect of ticlopidine on the cutaneous circulation in peripheral vascular disease. AB - To assess the effect of ticlopidine on the cutaneous circulation, 25 patients with lower limb ischemia were investigated just before and at two hours after being given a 200 mg oral dose of ticlopidine. The transcutaneous partial pressure of oxygen (PtcO2) and the skin temperature were determined at 35 limb sites and 9 chest walls sites. Both the PtcO2 and the skin temperature were significantly increased at two hours after the administration of ticlopidine (p < 0.01). The findings suggest that ticlopidine can improve the cutaneous microcirculation in patients with peripheral vascular disease. PMID- 8342880 TI - Platelet-derived growth factor release and antiplatelet treatment with low-dose acetylsalicylic acid. AB - Platelet-derived growth factor (PDGF) and beta-thromboglobulin (beta-TG) are released from alpha granules during platelet activation. PDGF may play a role in the development of atherosclerosis and the late restenosis after percutaneous transluminal coronary angioplasty (PTCA). The effect of acetylsalicylic acid (ASA) on PDGF release was studied in healthy volunteers before and twelve hours after ingestion of 300 mg ASA. PDGF, beta-TG, and thromboxane B2(TxB2) were measured by radioimmunoassay (RIA) in serum and in platelet rich plasma (PRP) after submaximal stimulation with collagen. TxB2 decreased significantly from 0.9 +/- 0.3 ng/(mL x 10(6) platelets) to 0.006 +/- 0.005 ng/(mL x 10(6) platelets) (mean +/- SD) in serum after ASA ingestion while PDGF and beta-TG remained unchanged. Measurements in PRP after stimulation with collagen showed a significant decrease in PDGF (from 21.5 +/- 1.4 pg/(mL x 10(6) platelets) to 1.8 +/- 4.1 (pg/mL x 10(6) platelets), in beta-TG (from 21.0 +/- 13.3 ng/(mL x 10(6) platelets) to 2.2 +/- 1.4 ng/(mL x 10(6) platelets)) and in TxB2 (from 143.6 +/- 80.7 pg/(mL x 10(6) platelets) to 0.5 +/- 0.6 pg/(mL x 10(6) platelets)) after treatment with ASA. In conclusion low-dose ASA inhibits collagen-induced release of both beta-TG and PDGF in PRP and TxB2-synthesis in PRP and serum. PMID- 8342881 TI - Hypoxia-induced activation of endothelial cells as a possible cause of venous diseases: hypothesis. AB - Blood stasis in leg veins is a situation commonly linked to the development of venous diseases such as varicoses. Such a stasis will provoke an ischemia, thus decreasing oxygen availability to tissues. Owing to its localization between blood and tissue, endothelium is the first target of this insult. The authors develop here a hypothesis in which the effect of oxygen deprivation on the functional state of the endothelium is the starting point of a cascade of events leading to the disorganization of the vessel wall typical of these pathologies. When venous human endothelial cells obtained from umbilical cords (HUVEC) are exposed to hypoxic conditions they become activated without change in their viability. The synthesis of a proinflammatory molecule (PAF, platelet-activating factor) and the adhesion of human polymorphonuclear neutrophils (PMN) on HUVEC are markedly increased during hypoxia incubation. These two processes are related to a calcium-dependent activation of endothelial cells due to a decrease of adenosine triphosphate (ATP) availability during hypoxia. Adherence of neutrophils to endothelial cells is the first step of diapedesis, which leads to the infiltration of these cells in the media of the veins, where they affect the smooth muscle cells and the connective tissue, leading to tissue alterations typical of the venous pathologies. The authors propose that this sequential process which originates from a reduction in oxygen availability and which involves different cell type as one main cause of the venous disorders, in addition to genetic, hormonal, and mechanical factors. PMID- 8342882 TI - Absence of enhancement of spontaneous echocardiographic contrast by thrombocytosis in a patient with left ventricular aneurysm, primary thrombocythemia, and von Recklinghausen neurofibromatosis: a case report. AB - A thirty-eight-year-old man with primary thrombocythemia, von Recklinghausen neurofibromatosis, and myocardial-infarction-related left ventricular aneurysm with spontaneous echocardiographic contrast was followed up, suggesting that: 1. Neurofibromatosis may promote silent myocardial infarction or ischemia. Whether involvement of cardiac sensory nerves is a possible underlying mechanism remains nevertheless uncertain. 2. Platelets, whose role in the genesis of spontaneous echocardiographic contrast has been advocated, are probably not involved in this phenomenon, even in large numbers. PMID- 8342883 TI - Mobile string-like thrombus on the calcified aortic valve in cardioembolic stroke -a case report. AB - The calcified aortic valve has been associated with being a possible source of emboli in cardioembolic stroke. However, thrombus on the calcified aortic valve has not been identified with two-dimensional echocardiography. A seventy-two-year old woman with calcified aortic stenosis was admitted with brain embolism. She had not previously received any platelet antiaggregant or anticoagulant. At admission, two-dimensional echocardiography demonstrated a mobile string-like abnormal echo attached to the calcified aortic valve, which showed regression and enlargement repeatedly during admission. No symptoms or clinical data suggested infective endocarditis or nonbacterial thrombotic endocarditis. After commencement of antiplatelet therapy, the abnormal echo regressed and disappeared. She continued to take the medication for seven months and then discontinued. Three months later, she developed recurrence of stroke, and an abnormal echo on the calcified aortic valve was again detected by two-dimensional echocardiography. The authors believe that the abnormal echo on the calcified aortic valve was thrombus and that it was the embolic source. Calcified aortic valve may thus be a causative lesion for mobile string-like thrombus. Two dimensional echocardiography should be performed repeatedly in patients with calcified aortic valve and brain embolism. PMID- 8342884 TI - Forward Doppler ophthalmic artery flow in patients with extracranial carotid artery occlusion--a case report. AB - The authors report 2 cases of common carotid artery (CCA) occlusion and 4 cases of extracranial internal carotid artery (ICA) occlusion with forward Doppler ophthalmic artery flow. The compression test during Doppler study showed that the ophthalmic artery flow was reduced to zero when compressed contralateral to the CCA in 1 case of CCA occlusion and when compressed ipsilateral to the CCA in all 4 cases of ICA occlusion. The angiograms showed that in the 2 cases of CCA occlusion, 1 had the ophthalmic artery originating from the anterior communicating artery, and the other had subclavian steal syndrome with a reversed vertebral flow. In 3 of the 4 cases of ICA occlusion, the ophthalmic artery was found to originate from the ipsilateral middle meningeal artery. Their findings suggest that in cases of extracranial carotid artery occlusion, the forward ophthalmic artery flow is supplied from the contralateral CCA in cases of CCA occlusion and from the branches of the ipsilateral external carotid artery in cases of ICA occlusion, and the vertebrobasilar system plays a less important role. PMID- 8342885 TI - Isolated tuberculous pericarditis still exists: a case history. AB - A fifty-four-year-old woman from a high socioeconomic class developed acute isolated tuberculous pericarditis, three years after her sister had recovered from such disease. She was treated successfully by a triple drug regimen including isoniazid, rifampin, and ethambutol. PMID- 8342886 TI - Leiomyosarcoma of the inferior vena cava causing Budd-Chiari syndrome--a case report. AB - A forty-eight-year-old Japanese woman with leiomyosarcoma of the inferior vena cava presenting as Budd-Chiari syndrome is reported. A large tumor originating from the venous wall grew into the lumen, obstructing the hepatic vein, and extended up to the right atrium. Although this is a very rare tumor, care should be taken in order to make an early diagnosis and manage the condition effectively. PMID- 8342887 TI - Can we relax during spirometry? PMID- 8342888 TI - Trial of standard versus modified expiration to achieve end-of-test spirometry criteria. AB - To assess whether satisfying American Thoracic Society (ATS) end-of-test spirometry criteria can be enhanced by modifying the patient's expiratory technique, we conducted a cross-over trial of two expiratory techniques in 48 patients with a range of pulmonary functions (Group 1, n = 12: FEV1/FVC < 0.45; Group 2, n = 11: FEV1/FVC, 0.45 to 0.60; Group 3, n = 16: FEV1/FVC, 0.61 to 0.74; Group 4, n = 9: FEV1/FVC > or = 0.75). After randomizing the order of testing, each patient performed three exhalations using a "standard" forced expiratory maneuver and a modified expiratory technique consisting of an initial maximal expiratory effort followed by a "relaxed expiration" for as long as possible. Patients initiated "relaxed expiration" when instructed by the supervising technician, who issued the instruction to relax when expiratory airflow fell to < or = 200 ml/s (as determined by flow-volume loop analysis). ATS end-of-test criteria were satisfied significantly more often using the modified expiratory technique (58.3% of testing sessions) than using the standard technique (18.7% of sessions, p = 0.001) because of prolongation of the forced expiratory time (FET) with the modified technique in all patient groups. In the 38 patients with FEV1/FVC < or = 0.75, the largest FVC and FET rose significantly using the modified expiratory technique, without compromising the largest FEV1 in any group. In patients with FEV1/FVC > or = 0.75, FET increased without concomitant changes in FVC or FEV1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342889 TI - Tumor necrosis factor and endotoxin do not directly affect in vitro diaphragm function. AB - Ventilatory pump failure can occur in the setting of severe infection. Recent in vivo studies have shown a significant decrease in diaphragm force production in rats with pneumococcal sepsis and sepsis secondary to Escherichia coli endotoxin. We hypothesized that diaphragm impairment during sepsis may be mediated by a direct effect of tumor necrosis factor-alpha (TNF) or endotoxin. To test this hypothesis we studied the mechanical characteristics of isolated rat diaphragm strips in tissue baths containing rTNF-alpha or endotoxin and compared the results with control strips. The strips were stimulated to contract isometrically in the tissue baths that were aerated with 95% O2-5% CO2. Baseline force frequency determinations were made at 60 min. Following this, the strips were fatigued over a 4-min period (20 Hz, 0.33-s trains, 1 train/s) and force frequency relationships determined 30 s, 10 min, and 60 min post-fatigue. There were no significant differences found between control and experimental strips in any aspect of contractile function tested, including force-frequency characteristics, fatiguability, and recovery from fatigue. Using an isolated cell line assay (L929), we found evidence of attenuated cytotoxicity of TNF at 26 degrees C compared with 37 degrees C. Therefore, we repeated the experiments studying the effects of TNF on in vitro muscle at 37 degrees C. We once again found no effect of TNF on contractile function. We conclude that the impairment of diaphragm function during sepsis is not mediated by a direct effect of TNF or endotoxin. PMID- 8342890 TI - Factors determining pulmonary function in adolescent idiopathic thoracic scoliosis. AB - Adolescent idiopathic thoracic scoliosis may lead to severe pulmonary impairment and early death, but the responsible factors are poorly understood; pulmonary function is only weakly related to the angle of scoliosis. We performed a cross sectional study using multivariate analysis to identify the individual and additive influence of different features of spinal deformity and nonstructural factors on pulmonary impairment. Pulmonary function was assessed by measuring lung volumes and diffusing capacity, with a priori selection of vital capacity (expressed as percentage of predicted, % VC) as the primary index of pulmonary impairment. Radiologic and physiologic measurements were made independently in 66 subjects who had not previously had spinal surgery. Angle of scoliosis (p = 0.01) was one of four features of spinal deformity associated with reduced % VC; greater number of vertebrae involved (p = 0.007), cephadal location of the curve (p = 0.04), and loss of the normal thoracic kyphosis (p = 0.002) made an equal and additive contribution to pulmonary impairment. Spinal deformity led to reductions in VC, primarily by reducing TLC. Spinal column rotation, respiratory muscle strength, and duration of the curvature were not related to pulmonary function (p > 0.05). We conclude that features of the spinal deformity are the major determinants of pulmonary impairment in idiopathic thoracic scoliosis but that the relationship between deformity and impairment is complex. The severity of pulmonary impairment cannot be inferred to a clinically useful extent from the angle of scoliosis alone. PMID- 8342891 TI - Factors influencing work capacity in adolescent idiopathic thoracic scoliosis. AB - The factors contributing to reduced work capacity (disability) in adolescent idiopathic thoracic scoliosis are poorly understood. We performed a cross sectional study using multivariate analysis to identify the individual and additive influence of spinal deformity, pulmonary impairment, and muscular function on work capacity in 79 subjects with idiopathic scoliosis (angle of scoliosis 45 +/- 18.5 degrees, SD). Work capacity was measured using an incremental cycle test, and the cardiorespiratory response to exercise was compared with that of normal subjects. Work capacity was reduced (% Wcap, 86%; 95% CI 81.9 to 89.7), indicating significant disability. The % Wcap was unrelated to the nature and extent of spinal deformity (p > 0.05). Leg muscularity and pulmonary impairment had an additive influence on work capacity, the relationship with muscularity being the stronger of the two. Independently of muscularity and pulmonary impairment, a high heart rate response at submaximal work rates was also associated with a reduced work capacity. Ventilation was normal for metabolic demands. During exercise, the tidal volumes of scoliotic subjects were reduced in proportion to the vital capacity. We conclude that disability occurs with mild to moderate idiopathic scoliosis and appears to be related to a combination of reduced ventilatory capacity, reduced muscularity, and cardiovascular deconditioning. These findings suggest that physical activity should be encouraged in subjects with idiopathic scoliosis to maintain peripheral muscle and cardiovascular conditioning, thereby minimizing disability. PMID- 8342892 TI - Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension. AB - To investigate endothelium-dependent and endothelium-independent nitric oxide (NO) mediated pulmonary vasodilation in patients with chronic obstructive lung disease (COLD), we examined the responses to incremental infusion rates of acetylcholine (ACh) or inhaled NO on hemodynamic and gas exchange. In 13 patients, ACh (15 mg/min) decreased pulmonary artery pressure (Ppa) from 31 +/- 1 to 28 +/- 1 mm Hg (p < 0.01) and systemic arterial pressure while increasing cardiac index from 3.7 +/- 0.4 to 4.7 +/- 0.4 L/min/m2 (p < 0.01). Inhaling 40 parts per million (ppm) NO decreased Ppa from 32 +/- 1 to 26 +/- 1 mm Hg (p < 0.001) with no associated hemodynamic change. ACh reduced PaO2 from 57 +/- 3 to 48 +/- 2 mm Hg (p < 0.01) and increased venous admixture (QVA/QT) from 35 +/- 3 to 45 +/- 3% (p < 0.01). Inhaling 40 ppm NO increased PaO2 from 57 +/- 3 to 60 +/ 3 mm Hg (p < 0.01) and decreased QVA/QT from 36 +/- 3 to 32 +/- 3% (p < 0.01). Pulmonary vascular resistance changes were similar in response to 40 ppm NO or 15 mg/min ACh. In COLD patients, ACh produces both pulmonary and systemic vasodilation but impairs arterial oxygenation whereas inhaled NO induces selective pulmonary vasodilation while improving gas exchange. The resistance to ACh in some patients could be related to pulmonary endothelial dysfunction. PMID- 8342893 TI - Bicarbonate does not increase left ventricular contractility during L-lactic acidemia in pigs. AB - Lactic acidosis decreases left ventricular contractility, but whether bicarbonate increases left ventricular contractility during lactic acidosis in vivo is controversial. Therefore, we measured hemodynamics and left ventricular mechanics before and after bicarbonate administration during L-lactic acid infusion in 15 anesthetized pigs. The pigs were beta-blocked and atrially paced to minimize indirect effects of acidosis on contractility. We measured mean arterial pressure, left ventricular end-diastolic pressure, thermodilution cardiac output, left ventricular pressure (Miller catheter), and left ventricular volume (three orthogonal pairs of ultrasonic crystals). Left ventricular contractility was assessed primarily using the slope (Emax) of the end-systolic pressure-volume relationship. While PCO2 was kept constant, 0.2 M L-lactic acid was infused, which reduced arterial pH to 7.05 +/- 0.06. Animals were then randomized to receive either 1 M NaHCO3 (n = 8), which increased pH to 7.45 +/- 0.11, or an equivalent amount of 1 M NaCl (n = 7). Bicarbonate decreased mean arterial pressure (105 +/- 20 to 95 +/- 39 mm Hg, p < 0.05) but did not increase cardiac output. These effects were not significantly different from the effects of saline. Bicarbonate did not significantly increase Emax (4.2 +/- 0.8 to 4.9 +/- 0.8 mm Hg/ml) and was indistinguishable from saline (5.0 +/- 0.7 to 5.2 +/- 0.7 mm Hg/ml). We conclude that bicarbonate infusion does not directly increase left ventricular contractility during lactic acidemia in pigs within this pH range. PMID- 8342894 TI - Effects of periodic obstructive apneas on venous return in closed-chest dogs. AB - With sleep apnea syndrome, mean cardiac output (CO) may fall. This implies a fall in venous return (VR) that is equal to the product of the pressure gradient for VR (GVR)--mean circulatory pressure (MCP)--right ventricular end-diastolic pressure and the conductance for VR (Gv). During airway obstruction there could also be shifts of blood volume between central and peripheral circulatory compartments. We studied these parameters in anesthetized closed-chest, spontaneously breathing dogs when hypoxia occurred (room air [RA] breathing) and when hypoxia was prevented (100% O2 breathing). Obstructive apneas were induced by completely occluding the endotracheal tube at end expiration for 1 min and allowing 1 min of spontaneous ventilation. During RA apneas, arterial PO2 decreased to 32.7 +/- 6.1 mm Hg (p < 0.01). Apnea reduced respiratory effort rate by 22.0 to 37.0% and was associated with inspiratory airway pressure swings in both RA and O2 of approximately -16.0 mm Hg. During apnea, on RA and O2 heart rate and mean arterial pressure decreased by 20 to 30 beats/min and by 8 to 12 mm Hg, respectively. On RA, CO decreased by 7.0% (not significant). In contrast, on O2, CO increased by 21.0% (p < 0.01). With RA apneas, GVR and MCP increased by 55% (p < 0.05) and Gv decreased by 63% (p < 0.05). On O2, there were no changes in GVR or Gv, and changes in CO were predictable from the baseline VR curve. With O2 there was an increase in central blood volume by 21.0% (p < 0.01) during the apneic phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342895 TI - Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure. AB - Periodic breathing with central apneas during sleep is typically triggered by hypocapnia resulting from hyperventilation. We therefore hypothesized that hypocapnia would be an important determinant of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with congestive heart failure (CHF). To test this hypothesis, 24 male patients with CHF underwent overnight polysomnography during which transcutaneous PCO2 (PtcCO2) was measured. Lung to ear circulation time (LECT), derived from an ear oximeter as an estimate of circulatory delay, and CSR-CSA cycle length were determined. Patients were divided into a CSR-CSA group (n = 12, mean +/- SEM of 49.2 +/- 6.3 central apneas and hypopneas per h sleep) and a control group without CSR-CSA (n = 12, 4.9 +/- 0.8 central apneas and hypopneas per h sleep). There were no significant differences in left ventricular ejection fraction, awake PaO2, mean nocturnal SaO2, or LECT between the two groups. In contrast, the awake PaCO2 and mean sleep PtcCO2 were significantly lower in the CSR-CSA group than in the control group (33.0 +/- 1.2 versus 37.5 +/- 1.0 mm Hg, p < 0.01, and 33.2 +/- 1.2 versus 42.5 +/- 1.2 mm Hg, p < 0.0001, respectively). Neither group had significant awake or sleep-related hypoxemia. In addition, CSR-CSA cycle length correlated with LECT (r = 0.939, p < 0.001). We conclude that (1) hypocapnia is an important determinant of CSR-CSA in CHF and (2) circulatory delay plays an important role in determining CSR-CSA cycle length. PMID- 8342896 TI - Use of capnography for assessment of the adequacy of alveolar ventilation during weaning from mechanical ventilation. AB - A prospective study was conducted to determine the reliability of noninvasive end tidal CO2 (PETCO2) monitoring as a reflection of arterial CO2 tension (PaCO2) during weaning from mechanical ventilation (MV). Simultaneous PaCO2 and PETCO2 determinations were compared during MV and again during a spontaneous breathing trial just before returning the patient to MV. Three groups of patients recovering from acute respiratory failure were evaluated. Group 1 consisted of 16 patients (28 observations) without parenchymal lung disease. Group 2 consisted of 22 patients (31 observations) with alveolar filling diseases. Group 3 was composed of 13 patients (22 observations) with emphysema. Significant Pearson correlation coefficients were demonstrated between PaCO2 and PETCO2 during both MV and spontaneous breathing in all three groups. Significant correlation was also demonstrated between the change in PaCO2 and the change in PETCO2 associated with weaning for each group; however, the degree of correlation varied between groups. Our data suggest that capnography offers a reasonable estimate of PaCO2 and changes in PaCO2 during weaning in patients without parenchymal lung disease. However, PETCO2 is less sensitive to changes in PaCO2 for patients with parenchymal lung disease, particularly patients with emphysema. Interpretation of capnographic data requires a full understanding of its limitations. An approach to capnographic monitoring during weaning is discussed. PMID- 8342897 TI - Tracheal gas insufflation augments CO2 clearance during mechanical ventilation. AB - A technique that improves the efficiency of alveolar ventilation should decrease the pressure required and reduce the potential for lung injury during mechanical ventilation. Alveolar ventilation may be improved by replacing a portion of the anatomic dead space with fresh gas via an intratracheal catheter. We studied the effect of intratracheal gas insufflation as an adjunct to volume cycled ventilation in eight sedated, paralyzed patients with a variety of lung disorders. Continuous flows of 2, 4, and 6 L/min were delivered through a catheter positioned 1 or 10 cm above the carina. Carbon dioxide production, inspiratory minute ventilation, and peak and mean airway pressures did not change over the range of flows tested. PaCO2 and dead space volume/tidal volume decreased significantly as joint functions of catheter flow and position (p < 0.001). The highest catheter flow (6 L/min) and most distal catheter position (1 cm above the carina) were the most effective combination tested, averaging a 15% reduction in PaCO2 (range 9 to 23%). Certain characteristics of the expiratory capnogram were helpful in predicting the observed reduction in PaCO2. Tracheal gas insufflation may eventually prove a useful adjunct to a pressure-targeted strategy of ventilatory management (in either volume-cycled or pressure controlled modes), particularly when the total dead space is heavily influenced by its anatomic component. PMID- 8342898 TI - Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation. AB - We studied the interrelations between gastric, pharyngeal, proximal, and distal airway bacterial flora in ventilator-associated pneumonia (VAP) on 36 patients with nosocomial pneumonia acquired during mechanical ventilation (MV) and 27 mechanically ventilated control subjects without pulmonary infection. Gastric, pharyngeal, and endotracheal (EA) sampling for quantitative cultures were performed upon all patients, as well as fiberoptic bronchoscopy with protected specimen brush (PSB) sampling. Mean bacterial and fungi colony counts were significantly increased in pharyngeal, EA, and PSB samples in patients with VAP compared with control subjects. The overall increase in colonization was due to gram-positive cocci in all samples. In addition, gram-negative bacilli and fungi mean counts increased significantly in PSB pneumonia samples versus control samples. However, mean gastric colonization was similar in both patients with VAP and control subjects. In the former group there was an increase in coincident microorganisms isolated from gastric, pharyngeal, and EA samples in relation to PSB samples compared with control samples. Among the different quantitative cultures analyzed, only those obtained from EA significantly correlated with PSB cultures in patients with pneumonia (r = 0.67, p = 0.001). In summary, the present study shows that the coincidence between microorganisms isolated in PSB cultures and those from gastric and oropharynx increase in MV patients with pneumonia, indicating that both reservoirs play a key role in the pathogenesis of pneumonia. Conceivably, preventing both gastric and pharyngeal colonization may reduce the incidence of ventilator-associated pneumonia. From all the noninvasive samples studied only endotracheal aspirate cultures were useful for inferring the etiology of some VAP pneumonias. PMID- 8342899 TI - Response time and reliability of three neonatal patient-triggered ventilators. AB - We studied the response time (RT) and reliability of three neonatal patient triggered ventilator (PTV) systems: the Draeger Babylog 8000, the Bear Cub enhancement module (CEM), and the Infrasonics Star Sync. In 10 adult rabbits, airway flow and pressure recordings showed the RT of the Star Sync to be shorter than that of the Bear CEM (53 +/- 13 versus 65 +/- 15 ms, p < 0.05), and both were shorter than that of the Babylog (95 +/- 24 ms, p < 0.01) by ANOVA. The RT of the Bear CEM and the Babylog increased significantly at decreased trigger sensitivity settings. All ventilators triggered successfully on assist-control (A/C). However, the Babylog had a higher rate of asynchrony on SIMV (30 +/- 25%) than the Bear CEM (1.1 +/- 0.3%) and the Star Sync (1.2 +/- 0.4%), p < 0.01. In 10 infants with respiratory failure, recordings of airway flow and pressure were made at ventilator inspiratory time (Ti) settings of 0.3, 0.4, and 0.5 s on assist-control and on SIMV at rates of 15, 30, 45, and 60 breaths/min. The Star Sync and Bear CEM triggered successfully on A/C (100%) and had low rates of asynchrony on SIMV (1 to 3%). The Babylog had a lower success rate on A/C (70 +/- 12%) and a higher rate of asynchrony on SIMV (29 +/- 30%) than the other two ventilators; p < 0.01. The lower reliability of the Babylog was due to its variable refractory period (0.2 to 0.5 s, to equal the set Ti).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342900 TI - Increased adherence of Staphylococcus aureus from cystic fibrosis lungs to airway epithelial cells. AB - Airway colonization by Staphylococcus aureus is a frequent feature of cystic fibrosis (CF). To assess the pathogenesis of selective colonization with this organism, we compared the capacity of S. aureus isolated from the respiratory tract of CF and non-CF patients to adhere to epithelial cells from the upper and lower airways of CF and control subjects. Bacterial adherence to bronchial epithelial cell lines was significantly greater for CF than for non-CF isolates (p < 0.001). Of 17 CF S. aureus isolates 12 adhered at a level > 1 bacterium per cell; this was true for only 1 of 14 non-CF isolates. CF S. aureus isolates also bound more avidly than non-CF isolates to ciliated (p < 0.05) and squamous nasal cells (p < 0.02) and buccal epithelial cells (p < 0.005) freshly harvested by scraping. Each S. aureus isolate bound with equal avidity to epithelial cells from CF patients and healthy individuals. Adherence was not related to sex, age, severity of pulmonary disease, presence of other microorganisms in the airways, or genotype of the CF hosts. Binding of S. aureus was blocked by proteinase treatment of organisms, suggesting that adherence is mediated by one or more peptide adhesins. We propose that the high prevalence of adherent S. aureus is due either to selection of adherent strains by CF airways or to induction of an adherent phenotype by factors residing at the CF airways surface. PMID- 8342901 TI - Bronchoscopy versus empirical therapy in HIV-infected patients with presumptive Pneumocystis carinii pneumonia. A decision analysis. AB - The outcomes of alternative strategies for the management of pulmonary complications in patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia were compared using a decision analysis model. A decision tree was constructed using baseline probabilities derived from published data and expert opinion. The case scenario analyzed was that of a patient not currently receiving anti-Pneumocystis prophylaxis who presents with moderate pulmonary symptoms and fulfills the Centers for Disease Control (CDC) criteria for presumptive P. carinii pneumonia. Two strategies were compared: (1) early bronchoscopy with appropriate therapy based on the results, and (2) empiric treatment for P. carinii (trimethoprim/sulfamethoxazole or pentamidine, and steroids) with delayed bronchoscopy in those not responding to 5 days of empiric therapy. The expected 1-month survival rate (with and without quality of life adjustment) was found to be essentially the same for the two strategies using the baseline probabilities, and the decision remained a toss-up within the clinically relevant range of published probabilities for P. carinii pneumonia in patients fulfilling the CDC criteria. Because early bronchoscopy does not offer any additional survival benefits and is associated with greater costs and disutility, empiric therapy would appear to be the superior management strategy in this scenario. PMID- 8342902 TI - Elevated levels of serum mucin-associated antigen in adult patients with cystic fibrosis. AB - Previous studies using the CA 19-9 antibody have demonstrated that serum mucin levels in patients with cystic fibrosis (CF) are elevated and that the degree of elevation relates to the age of the patient and possibly to his or her clinical status. However, CA 19-9 only recognizes the mucin-associated blood group sialyl Le(a+) antigen, so mucin levels cannot be measured in patients without Lewis antigens. The present study used the 17B1 monoclonal antibody to measure serum mucin levels in normal subjects, and in patients with CF, patients with chronic obstructive pulmonary disease (COPD), and patients with lung transplants. Serum mucin levels were 25 ng/ml (+/- 1 SEM, n = 8) in normal subjects, 13,853 ng/ml (+/- 1,281, n = 25) in patients with CF, and 25.5 ng/ml (+/- 1.9, n = 17) in patients with COPD. Patients with CF who were sialyl Le(a-b-) also had elevated serum mucin levels (715 +/- 152, n = 2). Serum mucin levels of six lung transplant recipients with CF were elevated compared with those in normal subjects (4,621 +/- 765 ng/ml), but they were not different from serum mucin levels in six lung transplant recipients without CF (5,307 +/- 1.677 ng/ml). Preliminary characterization of the serum mucin antigen showed that: (1) in CF sera, the antigen is polydisperse and smaller than the antigen in normal sera; (2) the mucin antigen is distinct from ABO blood group antigens. Serum mucin levels may be a useful marker to follow a specific patient's response to therapy. PMID- 8342903 TI - Activation of blood neutrophils in acute episodes of farmer's lung. AB - Farmer's lung often presents clinically as recurring acute episodes several hours after exposure to moldy hay. During these episodes the blood neutrophil count increases. Because activated neutrophils release toxic oxygen metabolites and proteinases, we hypothesized that the pulmonary reaction in farmer's lung may be induced by the secretory products of activated neutrophils. To evaluate this concept, we quantified the respiratory burst of separated blood neutrophils from patients with farmer's lung (n = 12) during standardized exposure tests with moldy hay. The respiratory burst of these cells was evaluated by measuring zymosan-stimulated and lucigenin-amplified chemiluminescence (CL). Asymptomatic farmers (n = 12) and normal volunteers with no prior exposure to moldy hay (n = 15) were used as control subjects. As expected, following exposure in the group of patients with farmer's lung, striking changes in VC, TLCO, and PaO2 were observed, whereas there were only minor changes in these parameters in both control groups. In all three groups a considerable increase in the blood leukocyte count was observed. The CL response of the blood neutrophils from patients with farmer's lung 6 h after exposure was significantly higher than before or 1 h after exposure (p < 0.05 for both comparisons), whereas there was no significant change in the CL response in either control group during the observation period. Our results indicate that antigen inhalation induces an increase in the number of circulating neutrophils in patients and controls, but in patients with an acute episode of farmer's lung the neutrophils are primed for an enhanced respiratory burst and may thereby damage the lung. PMID- 8342904 TI - Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5, and interferon-gamma cytokine gene expression. AB - Although corticosteroids are effective in improving asthma symptoms and bronchial responsiveness, their mechanism of action is unknown. We examined whether changes in bronchial responsiveness with corticosteroid therapy of asthma are accompanied by a reduction in cytokine gene expression and eosinophil infiltration in the airways. Bronchoalveolar lavage (BAL) was performed in 18 patients with moderate asthma before and after 2 wk of treatment with prednisolone, 0.6 mg/kg/day, or matched placebo in a randomized double-blind parallel group study. Cells were counted in BAL cytocentrifuge preparations, and the numbers of cells expressing cytokine mRNA were assessed by in situ hybridization using 35S-labeled RNA probes. When the actively treated and placebo groups were compared, there was a decrease in airway methacholine responsiveness (p < 0.01) after prednisolone. This was accompanied by a decrease in bronchoalveolar lavage eosinophils (p < 0.05), a reduction in the numbers of BAL cells per 1,000 expressing mRNA for interleukin-4 (IL-4, p < 0.01) and interleukin-5 (IL-5, p < 0.005), and an increase in numbers of cells expressing mRNA for interferon-gamma (p < 0.005). These results are compatible with the hypothesis that the beneficial effects of corticosteroids in asthma may result from modulation of cytokine production, with consequent inhibition of local bronchial eosinophilia. PMID- 8342905 TI - Role of leukotriene D4 in allergen-induced increases in airway smooth muscle in the rat. AB - The purpose of the study was to investigate whether allergen-induced hyperresponsiveness to methacholine and an increase in airway smooth muscle (ASM) in Brown Norway (BN) rats could be mediated by LTD4, an important mediator of allergic airway responses. Male BN rats, 8 to 12 wk of age, were sensitized with ovalbumin (OA). Rats were exposed 2 wk later to aerosols of saline (n = 6), OA (n = 8), or OA after pretreatment with the LTD4 antagonist MK-571 (2 mg/kg intraperitoneally, n = 9), on six occasions at 5-day intervals. Airway responsiveness to methacholine (the concentration required to double pulmonary resistance, EC200 RL) was measured immediately before the first aerosol exposure and 2 days after the last exposure. ASM was quantitated by morphometry, and areas were standardized for size using the epithelial basement membrane length (BM). Following OA challenges EC200 RL decreased from 6.5 to 3.1 mg/ml (p < 0.05) but did not change significantly after saline or OA exposures in MK-571-pretreated animals. ASM/BM2 in the large airways was significantly greater, 3.41 +/- 0.19 x 10(-3), after OA compared with 2.35 +/- 0.22 x 10(-3) for saline exposures (p < 0.01). The ASM/BM2 after OA exposures but with MK-571 pretreatment (2.75 +/- 0.25 x 10(-3)) was intermediate in value. The results indicate that both the increase in airway responsiveness and the increase in ASM following repeated antigen exposures appear to be mediated predominantly by LTD4. PMID- 8342906 TI - Chronic obstructive pulmonary disease. An original model of cognitive decline. AB - In order to characterize the neuropsychologic profile of patients with hypoxic hypercapnic chronic obstructive pulmonary disease (COPD), the performance of 36 patients with COPD 69 +/- 10 yr of age (mean +/- SD) on 19 tests exploring eight cognitive domains was compared with those of 29 normal adults (69 +/- 7 yr of age), 20 normal elderly adults (78 +/- 2 yr of age), 26 patients with Alzheimer type dementia (72 +/- 6 yr of age), and 28 with multi-infarct dementia (MID) (70 +/- 8 yr of age). The discriminant analysis of cognitive test scores showed that 48.5% of patients with COPD had a specific pattern of cognitive deterioration characterized by a dramatic impairment in verbal and verbal memory tasks, well preserved visual attention, and diffuse worsening of the other functions. The remaining patients with COPD were functionally classified as normal adults (12.1%), normal elderly adults (15.2%), those with MID (12.1%), and those with Alzheimer-type dementia (12.1%) according to discriminant analysis. Cognitive impairment was significantly and positively correlated with age (p < 0.05) and duration of hypoxic-hypercapnic chronic respiratory failure (p < 0.05). Because patients with COPD were receiving oxygen therapy from the beginning of oxyhemoglobin desaturation, results suggest that continuous oxygen therapy does not prevent or only partly prevents cognitive decline in COPD. Although some analogies between age-related and COPD-related cognitive decline are evident, a distinct cognitive profile was found in a large fraction of patients with COPD and it differs in several aspects from those of both normal and demented subjects. PMID- 8342907 TI - Inhibitory effect of staurosporine on protein kinase C stimulation of airway smooth muscle cells. AB - Phospholipid/calcium-dependent protein kinase (protein kinase C [PKC]) is a critical system in signal transduction of many different cells including airway smooth muscle (ASM) cells. We have previously shown that after administration of different phorbol esters, specific activators of PKC, characteristic electrical and contractile changes of ASM cells can be demonstrated. Similarly, our data showed that stimulation of PKC is implicated in the process of sensitization and the specific antigen challenge response of ASM cells. In this study we examined the effect of staurosporine, a microbial alkaloid, which has been reported to be a specific inhibitor of PKC, on sensitization- and specific antigen challenge induced electrical and contractile changes of ASM cells. The effect of staurosporine was compared with those of amiloride, furosemide, and compounds NA 0345 and H-7, both synthetic PKC inhibitors. We used ASM preparations isolated from adult male guinea pigs (Camm-Hartley strain). Changes in both membrane potential (Em), measured by a glass microelectrode technique, and isometric force, measured by copper-beryllium strain gauge, were continuously monitored. Experiments were conducted with optimal length (Lmax) of ASM preparations and at 37 degrees C. We found that the exposure of ASM preparations to staurosporine, NA 0345, H-7, amiloride, and furosemide (all in 10(-12) to 10(-4) M) had no measurable effect on the resting membrane potential or isometric force of ASM preparations. In contrast, pretreatment of ASM preparations with staurosporine, NA-0345, H-7, amiloride, or furosemide significantly attenuated (p < 0.001) phorbol myristate acetate-induced changes of ASM preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342908 TI - Antiasthma drug, ibudilast, inhibits neurogenic plasma extravasation in guinea pig airways. AB - We examined the effect of ibudilast, an antiasthma drug, on neurogenic microvascular leakage in guinea-pig airways by measuring extravasation of Evans blue dye. After intravenous pretreatment with atropine (1 mg/kg) and propranolol (1 mg/kg), bilateral vagal stimulation significantly increased nonadrenergic noncholinergic (NANC)-mediated leakage of dye in the trachea (Tr), the main bronchi (MB), and the central (cIPA) and peripheral (pIPA) intrapulmonary airways. Ibudilast (1.0 to 100 micrograms/kg given intravenously) did not affect basal leakage, but it significantly inhibited NANC-mediated plasma extravasation in a dose-dependent manner, with a maximal inhibition of 74.0% (Tr, p < 0.05), 89.1% (MB, p < 0.05), 91.4% (cIPA, p < 0.01), and 84.3% (pIPA, p < 0.05) at 100 micrograms/kg. Plasma extravasation induced by exogenous substance P (1 microgram/kg given intravenously) was not inhibited by ibudilast. Glibenclamide, an inhibitor of ATP-sensitive potassium channels, blocked the inhibitory effect of ibudilast. We conclude that ibudilast inhibits neurogenic leakage by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals via an ATP-sensitive potassium channel. PMID- 8342909 TI - Cigarette yields of tar and nicotine and markers of exposure to tobacco smoke. AB - Although cigarette yields of tar and nicotine have been declining since the early 1970s, little information is available for the general population on the consequences of their use on exposure to tobacco combustion products. In a population-based sample of 298 smokers, the majority of whom were Hispanic, we examined the relationships between yields of cigarettes currently smoked and levels of salivary cotinine and end-expired carbon monoxide. Spearman correlation coefficients between the current number of cigarettes smoked and cotinine (r = 0.52) or carbon monoxide (r = 0.51) were higher than correlations between the Federal Trade Commission (FTC) nicotine data and these same markers, 0.12 and 0.05, respectively. Correlations between FTC tar and carbon monoxide yields and the biologic markers were similarly weak. In multiple linear regression models, the current number of cigarettes smoked was the most important predictor of cotinine and carbon monoxide levels (p < 0.0001). The addition of FTC tar, nicotine, or carbon monoxide to the models explained little of the variability in cotinine or carbon monoxide levels. Because FTC yields of tar and nicotine are poor predictors of exposure to tobacco combustion products, subjects' reports of cigarette brand should not be used as a primary marker of exposure in epidemiologic investigations. Furthermore, smokers need to be advised about the limitations of cigarette yield information for predicting the potential for adverse health effects of smoking. PMID- 8342910 TI - Comparability of parent reports of respiratory illnesses with clinical diagnoses in infants. AB - In a cohort study of respiratory illnesses from birth through age 18 months, the investigators assessed the occurrence of illness by telephone reports of respiratory symptoms. To assess the comparability of illness events based on symptom reports with usual clinical modalities, a nurse practitioner examined children during illnesses, and office and clinic records of outpatient visits were reviewed. Respiratory illnesses were defined as symptom episodes of at least 2 days; lower respiratory illnesses included at least 1 day of either wet cough or wheeze. This report is based on 10,771 illnesses in the 1,315 subjects enrolled. Runny or stuffy nose was reported for most (93%) illnesses, wet cough in 33%, and wheeze in 6%. In comparison with the diagnoses made by a nurse practitioner, parent report of wet cough or wheeze was sensitive (93.4%) for detecting lower respiratory illnesses, but nonspecific with specificity of only 24.2%. The majority of the false-positive lower respiratory illnesses had the symptom of wet cough. The comparison of parent reports with outpatient records provided similar findings. Standardized reporting of respiratory illnesses can be achieved with a telephone surveillance system but classification of specific illnesses from the surveillance information may differ from diagnoses made by clinicians. PMID- 8342911 TI - Nasal secretion of the ozone scavenger uric acid. AB - Uric acid, an important scavenger of ozone, has been identified as the major low molecular weight antioxidant in baseline and cholinergically induced nasal secretions. The purpose of this study was to determine the specific tissue source of uric acid in airway secretions. The secretion of uric acid is increased by cholinergic stimulation and correlates closely with the secretion of lactoferrin (a nasal glandular protein), suggesting that submucosal glands are involved. Indeed, nasal turbinate tissue was found to contain uric acid. However, careful analysis of nasal turbinate tissue failed to reveal the presence of xanthine oxidase, the enzyme responsible for uric acid synthesis. These data suggest that uric acid might be taken up secondarily by glands from plasma. This possibility was strengthened by the observation that lowering the plasma urate level with probenecid concomitantly lowered urate secretion. These findings are consistent with the hypotheses that the principal source of uric acid in nasal secretions is plasma and that uric acid is taken up, concentrated, and secreted by nasal glands. PMID- 8342912 TI - Pharyngeal fat in obstructive sleep apnea. AB - Although most patients with obstructive sleep apnea (OSA) are obese, it is not known how obesity contributes to airway collapse during sleep. The purpose of this study was to determine whether the volume of adipose tissue adjacent to the pharyngeal airway in humans is related to the degree of OSA. We studied 30 subjects, nine without OSA and 21 with OSA; two subjects were studied before and after weight loss. Adipose tissue was detected with magnetic resonance imaging using T1-weighted spin echo sequences. The volume of adipose tissue adjacent to the upper airway was determined by measuring the volume of all pixels in the intensity range of adipose tissue within the region bounded by the ramus of the mandible, the spine, the anterior border of the soft palate, and the hard palate. Polysomnography was performed with conventional techniques. All subjects had a collection of adipose tissue adjacent to the upper airway; the volume of this adipose tissue correlated with the number of apneas plus hypopneas per hour of sleep (r = 0.59, p < 0.001). Both patients who lost weight and had fewer apneas and hypopneas had a marked decrease in the pharyngeal adipose tissue volume. We conclude that adipose tissue is deposited adjacent to the pharyngeal airway in patients with OSA and that the volume of this tissue is related to the presence and degree of OSA. PMID- 8342913 TI - Immunofluorescent analysis of plasma fibronectin incorporation into the lung during acute inflammatory vascular injury. AB - Incorporation of plasma fibronectin into tissues is believed to influence endothelial cell-cell interaction, as well as endothelial cell adhesion to matrix. We used immunofluorescent microscopy coupled with tissue extraction of noncovalently incorporated fibronectin to delineate the time course for matrix incorporation of soluble plasma-derived fibronectin into the lung of sheep during postoperative bacteremia. Adult sheep were surgically prepared with both lung and peripheral lymph fistulas. Sheep were anesthetized 2 days following surgery and injected intravenously with a sublethal dose of live Pseudomonas aeruginosa, which consisted of 5 x 10(8) live organisms suspended in 0.9% saline. Bacterial infusion elicited a 300% increase in lung transvascular protein clearance but no increase in peripheral transvascular protein clearance. Purified dimeric human plasma fibronectin (hFn), used as an "immunologic marker," was then infused intravenously (100 mg/sheep) into two additional groups of sheep (nonbacteremic control group and bacteremic experimental group) and allowed to mix with the plasma pool of endogenous soluble sheep fibronectin (sFn). Incorporation of the plasma-derived hFn into the lung matrix and its distribution in relation to endogenous sheep fibronectin in the matrix was assessed by dual-label immunofluorescence using antibodies specific to either sFn or hFn. Human fibronectin from the vascular compartment codistributed with endogenous sheep fibronectin in the lung matrix. Moreover, its deposition into the lung was markedly increased in postoperative bacteremic sheep compared with nonbacteremic control sheep. Increased hFn deposition in the lung with bacteremia was clearly apparent within 2 h. The hFn deposited in the lung was nonextractable using a heparin-urea tissue extraction buffer, suggesting its rapid covalent cross linking and incorporation into the lung matrix. Microscopic analysis of serial lung biopsies revealed focal areas of inflammation with an intense mononuclear infiltrate into the lungs by 2 h in the bacteremic sheep. Interstitial edema and vascular endothelial injury were observed by 4 h, with alveolar edema apparent over 6 to 8 h. Thus, postoperative bacteremia results in a rapid incorporation of plasma fibronectin into the lung matrix. This may be a physiologic mechanisms to stabilize the integrity of the lung vascular barrier. PMID- 8342914 TI - A new model of progressive pulmonary fibrosis in rats. AB - Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis. PMID- 8342915 TI - Enhanced production of IL-1 receptor antagonist by alveolar macrophages from patients with interstitial lung disease. AB - Alveolar macrophages (AM) produce various inflammatory and immunomodulatory cytokines. The objective of these experiments was to evaluate the production of IL-1ra, a specific receptor antagonist of IL-1, by AM from nonsmoking control subjects (n = 9), smoking control subjects (n = 6), and patients with interstitial lung disease (ILD) (n = 9). IL-1ra protein levels in cultured AM lysates and supernatants were determined by a specific ELISA; relative steady state IL-1ra mRNA levels were measured using a specific cDNA probe. Before culture the isolated AM from all subject groups contained undetectable IL-1ra mRNA and no IL-1ra protein in the cell lysates as determined by ELISA. AM from nonsmoking control subjects spontaneously produced IL-1ra protein after a 20 h culture in medium, approximately 12 ng/ml with around half in cell lysates. AM from smoking control subjects produced levels of IL-1ra that were similar to the levels in AM from nonsmokers. In contrast, AM from nonsmoking ILD patients (n = 6) produced high levels of IL-1ra spontaneously (approximately 28 ng/ml), with no enhancement observed when cultured on adherent IgG. Interestingly, AM from smoking ILD patients (n = 3) produced lower levels of IL-1ra protein (approximately 11 ng/ml) that were comparable to levels noted in smoking control subjects. AM from all three types of subjects produced decreased amounts of IL 1ra in response to LPS and enhanced amounts in response to GM-CSF. In general, IL 1ra steady-state mRNA levels correlated with protein production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342916 TI - Severe hemolysis due to a donor anti-D antibody after heart-lung transplantation. Association with lung and blood chimerism. AB - Hemolysis due to donor-derived red cell antibodies is a potential complication after minor ABO-mismatched solid organ transplantation. It has also been described in Rh-positive recipients receiving organs from previously isoimmunized Rh-negative donors. We report on a group O, Rh(D)-positive patient who received a heart-lung transplant from a group O, Rh(D)-negative donor presenting an anti-D antibody. Severe hemolytic anemia developed in the early postoperative period and lasted for 3 mo. Anti-D antibodies that were of donor origin were found in bronchoalveolar lavage fluid and serum. In addition, using the polymerase chain reaction for human leukocyte antigen class II genotyping, we were able to demonstrate the presence of a mixed population of donor and recipient cells in the lungs and the peripheral blood of the recipient. The chimeric state in the blood persisted until at least the fifty-seventh postoperative day. This first case report of hemolysis due to Rh(D) antibody after heart-lung transplantation emphasizes the need for routine red cell antibody screening of donors and for close monitoring of signs of red cell destruction in the recipient in cases of pretransplant donor isoimmunization. PMID- 8342917 TI - Paradoxical bronchoconstriction with nebulized albuterol but not with terbutaline. AB - A 40-yr-old woman with severe chronic asthma complained that her regular nebulized albuterol was exacerbating her symptoms. Changing to regular nebulized terbutaline resulted in a marked improvement in her peak flow readings. Double blind challenge with nebulized albuterol and terbutaline confirmed paradoxical bronchoconstriction with albuterol but not with terbutaline. This indicates that paradoxical bronchoconstriction to beta 2-agonists can be specific to the drug preparation used rather than a class effect, as has previously been suggested. PMID- 8342918 TI - Perception of breathlessness during early and late asthmatic responses. AB - We looked at the perception of breathlessness associated with bronchoconstriction during early (EAR) and late (LAR) asthmatic responses to inhaled antigens and its correlation with the rate of fall of expiratory flows. Twenty-eight asthmatics were studied (12 male, 16 female, 18 to 38 yr of age). Breathlessness was evaluated on a modified Borg scale (0 to 10) before each FEV1 measurement, obtained at regular intervals for as long as 8 h after the antigen challenge. The rate of the fall in FEV1 was calculated from the maximal percent fall obtained during the EAR or the LAR and the time lapse from the onset of the reaction to the maximal fall in FEV1. Ten subjects had an isolated early and 18 had a dual asthmatic response after allergen challenge. Dual responders perceived a similar percent fall in FEV1 (mean percent fall: EAR, 20.7 +/- 1.6%; LAR, 21.5 +/- 1.6%) more intensely during the EAR than during the LAR, with median Borg scores (range) of, respectively, 2.0 (0.5 to 4) and 0.5 (0 to 3.0) (n = 18, p < 0.001). The median rate of the fall in FEV1 was: EAR, 2.09 (0.77 to 6.6) %/min; LAR, 0.11 (0.05 to 0.36) %/min (n = 18, p < 0.001). The rate of the fall in FEV1 during either EAR or LAR was strongly correlated with the Borg scores; the slower the fall, the weaker the perception (p < 0.001). We conclude that LAR are poorly perceived compared with EAR and that this may be due to the temporal adaptation to the slow and progressive bronchoconstriction in LAR. PMID- 8342920 TI - Bronchoalveolar lavage in asthma. An update and perspective. PMID- 8342919 TI - Circulating immunoreactive endothelin-1 in children with pulmonary hypertension. Association with acute hypoxic pulmonary vasoreactivity. AB - To determine whether circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, are elevated in children with pulmonary hypertension and related to the degree of hypoxic pulmonary vasoconstriction, we measured arterial and mixed venous plasma concentrations of immunoreactive ET-1 (irET-1) in 13 children during cardiac catheterization. Clinical diagnoses in seven children with pulmonary hypertension (PH) included chronic lung disease (four children), congenital heart disease after surgical repair (two children), and primary ("reactive") pulmonary hypertension (one child). Blood samples were simultaneously obtained from pulmonary artery (venous) and systemic arterial sites during baseline conditions. Plasma irET-1 was elevated in children with PH (12.3 +/- 3.4 versus 3.6 +/- 0.7 pg/ml, PH versus non-PH; p < 0.01). Arterial/venous irET-1 ratios in the PH group (1.1 +/- 0.2) were not different from those in the non-PH group. During acute hypoxia, mean Ppa increased from 27 +/- 3 to 40 +/- 5 mm Hg. Basal irET-1 correlated strongly with the degree of elevation of mean Ppa during acute hypoxia (r = 0.69; p < 0.02). We conclude that irET-1 levels are often elevated in children with PH, and they are strongly correlated with pulmonary vasoreactivity during acute hypoxia. Whether elevated irET-1 levels contribute directly to or are markers of altered pulmonary vascular tone and reactivity in children with PH remains speculative. PMID- 8342921 TI - Diaphragmatic pacing. PMID- 8342922 TI - Microfixation of acute orbital fractures. AB - Microfixation techniques were used as an adjunct to the use of miniplates and screws in the acute treatment of fractures involving the orbit in 42 patients over a 2-year period. Miniplates were used in all fractures at the Le Fort I level and at the zygomatic-frontal suture in high-energy injuries. Microfixation was used to stabilize all other fractures of the zygomatic, nasoethmoid, and frontal areas. Problems with plate visibility and objectionable palpability through thin periorbital skin were eliminated. The use of microplates allowed more precise positioning of small fragments than possible with miniplates or interfragmentary wires. Fracture reduction remained clinically stable in the frontal and nasoethmoid areas. Microplates were inadequate to resist soft tissue deforming forces along the infraorbital rim and the zygomatic arch in high-energy injuries. PMID- 8342923 TI - Prevention of thrombosis by topical application of tissue factor pathway inhibitor in a rabbit model of vascular trauma. AB - The extrinsic pathway of coagulation is initiated when tissue factor complexes with factor VII. A naturally occurring protein inhibitor of this complex, tissue factor pathway inhibitor (TFPI), has recently been isolated and the cDNA coding for this protein cloned. We used a rabbit ear artery model of crush/avulsion injury and microvascular repair to investigate the efficacy of TFPI as a topically applied antithrombotic agent. Traumatized arteries treated through lumenal irrigation with normal saline vehicle (controls) achieved patency rates of 8% and 0% at 1 and 7 postoperative days, respectively. Heparin irrigation (10 U/ml) resulted in patencies of 40% at both evaluation times. In contrast, TFPI at a dose of 20 micrograms/ml (0.2 ml total volume; 10 minute exposure) yielded a 91% patency rate at 1 day and 73% at 7 days postoperatively (p < 0.0005 vs controls). Prothrombin time and activated partial thromboplastin time values were not altered after topical treatment with TFPI. Scanning electron microscopy revealed dramatically inhibited thrombogenesis upon the injured surfaces of TFPI treated vessels. These results suggest that TFPI used as a topically applied antithrombotic agent is effective for the prevention of thrombosis in microvascular anastomoses. PMID- 8342924 TI - The extended deep inferior epigastric pedicle flap for lower extremity reconstruction. AB - Large soft-tissue defects of the lower extremity can present a challenging reconstructive problem. The extended deep inferior epigastric pedicle flap is a versatile and reliable flap that can be used for the coverage of complex lower extremity soft-tissue defects as far distal as the knee. We reviewed our 5-year experience with 20 consecutive extended deep inferior epigastric pedicle flaps used to cover lower extremity defects. All wounds, including 4 soft-tissue defects of the knee, were successfully covered. Two minor complications occurred. Flap anatomy, surgical approach, and new refinements in flap design are presented. The indications for the flap and its role in ablative tumor surgery are discussed. This flap has proved to be versatile, easy to raise, and extremely hardy. The ample skin island with its large arc of rotation is well vascularized, healing well even in irradiated wounds, and the flap tolerates both postoperative pressure and radiation. PMID- 8342925 TI - The expanded forehead flap for nasal reconstruction. AB - A 3-year experience using forehead tissue expansion for nasal reconstruction is presented. The series includes 7 expansions in 6 patients with different degrees of nasal loss due to either cancer, trauma, or avascular necrosis. Balloon tissue expansion minimizes the well-known limitations and drawbacks found in using forehead flaps for nasal reconstruction. Technique, timing, and sequencing of procedures are discussed and compared with those of other authors. The complications of tissue expansion are few, but obtaining a satisfactory nasal reconstruction requires multiple operations over a period of time. A learning curve is necessary due to inadequate previous experience and new developments in tissue expanders. The results obtained were possible due to the excellent tissue provided by forehead expansion. PMID- 8342926 TI - Facial injuries from falling: age-dependent characteristics. AB - A retrospective analysis was undertaken of 108 patients with facial injuries from falling who presented at the Plastic Surgery Unit of the Toyo-oka Public Hospital from 1988 to 1990. Facial injuries from falling were common in little children, in those < 6 years of age comprising 45.4% of injuries. Age-dependent characteristic injury sites were found (i.e., in those < 2 years old, the forehead; in small children, the chin; in students, the lip; and in older persons, the cheek); this disparity can be explained by the mechanism of injury. The injury pattern also depended on age, varying activities, and tissue strength. In children of < 6 years of age, small lacerations on the forehead or chin were most common, but even conservative treatment could achieve good results. On the other hand, inadequate suturing by emergency room physicians brought on poor results. In adults, abrasions and traumatic tattoos occurring with late-night inebriation tended to develop some sequelae. PMID- 8342927 TI - Quantitative monitoring of capsular contraction around smooth and textured implants. AB - The purpose of this study was to assess the efficacy of textured silicone implants in reducing the incidence of capsular contracture. Each of 10 female New Zealand, albino rabbits received 2 saline-filled implants, 1 on either side of the lateral chest wall. The surface of 1 implant was smooth silicone, whereas the other implant's surface was textured silicone. Magnetic resonance imaging (MRI) scans of the implants were performed at 0, 9, 17, 26, 34, and 40 weeks after implantation. Data from the MRI scans were used to calculate the effective surface area of implants at each analysis interval. This technique provided a noninvasive method of monitoring implant contraction as a function of time. Eight rabbits completed the study. Four of 8 smooth implants developed contractures, whereas none of the textured implants developed contracture. For the 4 smooth implants that developed contractures, MRI scans calculated 72 +/- 12% contraction at 17 weeks, but the Baker palpation test detected only mild firmness. From 17 to 40 weeks, the mean percentage of contraction for these implants changed minimally, but their mean Baker score increased from mild to severe (II to IV). Quantitative data from MRI scans were much more predictive of final implant contraction than palpation (Baker test), applanation tonometry, or indentation tonometry. The latter two tests only detected the final stages of severe implant contraction. PMID- 8342928 TI - Irradiation effects on wound contraction using a connective tissue model. AB - To analyze irradiation effects on wound contraction, fibroblasts harvested from human oral mucosa were irradiated (single 2-, 4-, 6-, 8-, and 10-Gy exposures of x-rays). The irradiated fibroblasts were examined for growth ability, and they were cultured three-dimensionally in hydrated collagen gels. The irradiation inhibited growth of fibroblasts and contraction of collagen gels in a dose dependent manner. In addition, inhibition depended on the duration after exposure. The organization of actin filaments of fibroblasts in this model was examined with fluorescent dye-conjugated phalloidin. Many elongated cell projections were formed in cells of the control group, but the cell projections were almost disrupted in the irradiated cells. X-ray irradiation is thus shown to inhibit wound contraction by affecting the organization of actin filaments in fibroblasts. PMID- 8342929 TI - Tissue oxygenation and blood flow on specialized and conventional hospital beds. AB - Despite the widespread use of specialty bed products, the physiological mechanism of their benefit has not been evaluated. In this study, healthy subjects were used to study transcutaneous oxygen tension (TcPo2) and laser Doppler blood flow in pressure sore-prone areas on air-fluidized, low-air-loss, and adjustable air mattress beds relative to a standard hospital mattress with and without an egg crate mattress overlay. Measurements were obtained over the sacrum with the subject in the prone and supine positions, and over a greater trochanter with the subject in the prone and 90-degree lateral positions. Our results on healthy volunteers suggest that the specialty bed products maintain TcPo2 better than a standard bed when tissue is weighted. Further, the Clinitron had significantly higher TcPo2 when weighted than each of the other beds. Laser Doppler blood flow was much more variable. The weighted trochanter on the standard bed had the lowest blood flow, which is consistent with the TcPo2 readings. However, the variability made the laser Doppler flow data less valuable than the TcPo2. In conclusion, these data indicate that several products, particularly the Clinitron, maintain TcPo2 of weight-bearing tissue, which may be an important mechanism in protecting against pressure sores. PMID- 8342930 TI - Marginal eyelid reconstruction with a composite skin-muscle-mucosa graft from the lower lip. AB - Marginal defects of the eyelid were repaired using skin-muscle-mucosa composite grafts from the lower lip without cartilage support in 2 patients. The method is a simple one-stage procedure and takes little time to perform. Because of the wide contact between the grafts and the recipient sites, grafting was successful. Texture and color match is not too problematic in elderly persons. PMID- 8342931 TI - Asymmetrical hypersensitivity to bovine collagen. AB - We report a unique patient with true asymmetrical hypersensitivity to bovine collagen. Hypersensitivity is the development of an inflammatory response at a treatment site after a negative skin test. She developed an inflammatory response in only one of two simultaneously injected sites. About 1.5% of patients with a negative skin test have a hypersensitivity reaction consisting of firmness, erythema, and swelling. The signs and symptoms generally resolve spontaneously in a few months. PMID- 8342932 TI - Scalp flap rotation with primary donor site closure. AB - A 57-year-old man with a 7-cm defect of the left temple underwent reconstruction with a large scalp rotation flap that shifted the donor defect to the back of the neck so that it could be closed primarily. This approach, also used successfully in 7 other patients with similar defects, avoided the need for an unsightly skin graft in the donor site while providing tissue with a color and texture that blended well with the surrounding forehead and facial skin. Primary closure of the donor site reduces scalp flap morbidity and improves the overall aesthetic outcome. PMID- 8342933 TI - Myonecrosis as a sequela of calf implants. AB - Calf augmentation using alloplastic implants primarily is intended to enhance body contour. Usually this is a safe and efficacious procedure. However, in this unique report, significant myonecrosis occurred as a direct consequence of calf implantation, which resulted in a residual functional disability as well as aesthetic deformity. An awareness of the potential for a similar catastrophe hopefully will mitigate against future overzealous attempts at augmentation. PMID- 8342934 TI - Successful treatment of coccidioidomycosis osteomyelitis in an infant. AB - A 10-month-old Hispanic male infant with expansile lesions of the third metacarpal and proximal phalanx positively diagnosed as Coccidioides immitis osteomyelitis is presented. Treatment consisted of combined surgical debridement and systemic antifungal therapy and resulted in complete resolution of the lesions. Treatment was guided by clinical response and complement fixation titers. Osteomyelitis is a relatively infrequent manifestation of disseminated coccidioidomycosis. Neonates and infants appear to be more susceptible to the development of dissemination, but less likely to develop toxicity due to systemic therapy. Current therapy consists of concomitant surgical excision of involved lesions and systemic antifungal therapy. Complement fixation titers correlate closely with clinical response to therapy and are useful in detecting subclinical recurrences. PMID- 8342935 TI - Neovaginal procidentia. AB - Split-thickness skin grafts combined with an omental pedicle is a popular method of vaginal reconstruction. An unusual case of neovaginal prolapse presenting 3 months after construction is presented. Sacral colpopexy using autogenous fascial tissue allowed for both anatomical and functional correction of this neovagina. PMID- 8342936 TI - A reconstructive surgeon's taste in art: Dr Peter Parker and the Lam Qua oil paintings. AB - Hidden within the basement archives of Yale University's Historical Medical Library lie the original oil painting collection and personal papers of the first American surgeon to practice in China. The Reverend Dr Peter Parker, a graduate of Yale, established the first American hospital in Guangzhou (formerly Canton) in 1835 and successfully introduced Western surgical techniques including amputation, anesthesia, and reconstructive surgery. In addition to this distinguished career of medical missionary service, Parker commissioned the Chinese artist Lam Qua to paint a fascinating series of portraits depicting patients with extreme tumor growths. In this article, Parker's own journals are examined to reveal both his missionary zeal and his frustrations working in China. Selected examples of the Lam Qua paintings are presented along with Parker's corresponding patient descriptions. These detailed patient reports give insight into the extent of surgical pathology as well as the relative brutality of surgical techniques in the early to mid-1800s. The historical significance of the Peter Parker-Lam Qua collaboration within the context of the Western transformation of Chinese art and medicine is also discussed. PMID- 8342938 TI - The best and the brightest. PMID- 8342937 TI - The cleft palate gag line: connect the Dotts. AB - The origin of the Dott mouth gag is discussed and the various modifications of this instrument are listed chronologically. A personal modification to allow surgery of the tongue is described. PMID- 8342939 TI - Re: Accessory abductor digiti minimi muscle originating proximal to the wrist causing symptomatic ulnar nerve compression. PMID- 8342940 TI - Re: The subcutaneous forehead lift with an anterior hairline incision. PMID- 8342941 TI - Re: The transverse gracilis musculocutaneous flap. PMID- 8342942 TI - Identification and localization of a novel cathepsin S-like proteinase in guinea pig spermatozoa. AB - Guinea pig spermatozoa were found to contain a novel cysteine proteinase that most closely resembled lysosomal cathepsin S. The responsible enzyme was shown to have an acrosomal localization. Like the cathepsin S of lymphocyte-rich tissues, e.g., lymph nodes and spleen, the spermatozoal enzyme digested protein substrates such as hemoglobin and Azocoll optimally at about pH 3.5 in the presence of pepstatin. No appreciable action was manifested in the range of pH 5-6 on protein substrates nor on the 7-(4-methyl)coumarylamide (NMec) derivatives of peptides commonly employed for the fluorometric assay of cathepsins B (benzyloxycarbonyl (Z)-Arg-Arg-NMec), H (Arg-NMec), and L (Z-Phe-Arg-NMec). Like spleen cathepsin S, the sperm enzyme selectively hydrolyzed Z-Phe-Arg-NMec, but its activity was uncharacteristically limited to a pH range of 3.0-3.5, where it displayed a typical high sensitivity to sulfhydryl reagents (HgCl2, mersalyl acid, iodoacetate), leupeptin, Z-Phe-Phe-CHN2, and L-trans-epoxysuccinylleucylamido(3 methyl)butane. Gossypol (a male antifertility agent) was also inhibitory. Inhibition by the mercurial sulfhydryl reagents was completely reversible with dithiothreitol. Pepstatin, a potent inhibitor of aspartic proteinases, and serine proteinase inhibitors (phenylmethylsulfonyl fluoride, benzamidine) were ineffective. Other properties displayed by the sperm extract that were uniquely characteristic of cathepsin S included stability under alkaline conditions, and a greater rate of hydrolysis when the P2-phenylalanine of the assay substrate was replaced by two aliphatic residues, as in Z-Leu-Leu-Arg-NMec. PMID- 8342943 TI - Characterization of glutathione transferase from Xanthomonas campestris. AB - A single form of glutathione transferase (Xc-GST-4.5) having an isoelectric point at pH 4.5 was resolved from Xanthomonas campestris cytosol by affinity chromatography and isoelectric focusing. HPLC,N-terminal amino acid sequence, and SDS-PAGE analyses indicate that Xc-GST-4.5 is composed of two identical subunits, each with a molecular mass of 22 kDa. As indicated by its substrate specificity, immunological reactivity, and CD spectra, as well as by its N-terminal amino acid sequence, Xc-GST-4.5 appears to be distinct from the other bacterial glutathione transferases, Pm-GST-6.0 and Sm-GST-7.3, previously purified from the cytosolic fraction of Proteus mirabilis and Serratia marcescens. Xc-GST-4.5 also appears to be distinct from the GST so far purified from other sources. PMID- 8342944 TI - Biosynthesis of vicinal dihydroxy fatty acids in the red alga Gracilariopsis lemaneiformis: identification of a sodium-dependent 12-lipoxygenase and a hydroperoxide isomerase. AB - Biosynthesis of the vicinal diol fatty acid (12R,13S)-dihydroxy-(5Z,8Z,10E,14Z) eicosatetrae noic acid from arachidonic acid was studied in preparations of the red alga Gracilariopsis lemaneiformis. The transformation consisted of initial 12 lipoxygenase-catalyzed oxygenation of arachidonic acid into (12S)-hydroperoxy (5Z,8Z,10E,14Z)-eicosatetraeno ic acid followed by hydroperoxide isomerase catalyzed conversion of the hydroperoxide into (12R,13S) dihydroxyeicosatetraenoic acid. Short time incubations and trapping experiments with glutathione peroxidase revealed that (12S)-hydroperoxyeicosatetraenoic acid existed as a free intermediate in the overall conversion. The 12-lipoxygenase was mainly present in the soluble fraction of homogenate of G. lemaneiformis. Further, gel filtration experiments showed that the soluble 12-lipoxygenase was a protein having a molecular weight of 84,000-89,000. The enzymatic activity of 12 lipoxygenase isolated by gel filtration was weak; however, addition of 0.8-1 M sodium chloride to such desalted enzyme increased the activity 20-fold. Experiments with different salts revealed that sodium ion was specifically responsible for the stimulatory effect. Hydroperoxide isomerase was about equally distributed between the high speed supernatant and particulate fractions. Gel filtration of hydroperoxide isomerase present in the soluble fraction showed two peaks of activity corresponding to proteins having molecular weights of 220,000 or greater, and 40,000-45,000. The stereochemical course of the biosynthesis of vicinal diol fatty acids was determined using stereospecifically deuterated 6,9,12-octadecatrienoic acids. The 12-lipoxygenase-catalyzed reaction consisted of antarafacial hydrogen removal and oxygen insertion, whereas the hydroperoxide isomerase catalyzed an intramolecular oxygenation which occurred with retention of the configuration of the carbon atom hydroxylated. PMID- 8342945 TI - Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. AB - A full-length human cytochrome P450 (P450) 3A4 cDNA clone and four derivatives in which the N-terminus was modified were inserted into a pCW vector and used to transform Escherichia coli DH5 alpha cells. Little expression was seen with the native sequence; the highest level of expression (range of 40-110 membrane-bound nmol P450 liter-1) was achieved with a construct (NF14) in which residues 3-12 were deleted. In all of the constructs P450 was found primarily in the membranes. The modified P450 3A4 (construct NF14) showed typical P450 hemoprotein spectra. The protein was purified to electrophoretic homogeneity in a five-step procedure [nominally 23 nmol P450 (mg protein)-1]. For most purposes it was found to be more practical to purify the modified P450 3A4 to approximately 70% homogeneity [nominally 15 nmol P450 (mg protein)-1] in a simple two-step process. The modified P450 3A4 (NF14) or P450 3A4 purified from human liver could be mixed with rabbit liver NADPH-P450 reductase to achieve catalytic activities nearly as high as those found in human liver microsomes (on a nmol P450 basis), but the optimal reconstitution conditions included not only a mixture of phosphatidylserine, L-alpha-dilauroyl- and L-alpha-dioleoyl-sn-glycero-3 phosphocholines, cholate, and cytochrome b5 suggested by others but also glutathione during the preincubation. Several other thiols were found not to substitute in this role. Good catalytic activity was seen for nifedipine oxidation, testosterone 6 beta-hydroxylation, and the 8,9-epoxidation and 3 alpha hydroxylation of aflatoxin B1, reactions previously ascribed to the enzyme. These procedures provide a relatively convenient and reliable means of producing, purifying, and reconstituting a catalytically active and useful derivative of P450 3A4, a human P450 enzyme that has many roles in the oxidation of drugs and other xenobiotic chemicals. PMID- 8342946 TI - Free radical reductive degradation of vic-dibromoalkanes and reaction of bromine atoms with polyunsaturated fatty acids: possible involvement of Br(.) in the 1,2 dibromoethane-induced lipid peroxidation. AB - Bromine atoms generated upon reductive degradation of 1,2-dibromoethane and various other vic-dibromoalkanes have been shown to react with polyunsaturated fatty acids via both abstraction of bisallylic hydrogen and addition to the double bonds. The abstraction process occurs with 53, 68, and 77% efficiency from linoleic (18:2), linolenic (18:3), and arachidonic acid (20:4), respectively. The corresponding absolute rate constants have been evaluated to be 1.2 x 10(9), 1.8 x 10(9), and 5.1 x 10(9) M-1 s-1 for these three polyunsaturated fatty acids (PUFAs). The rate constants for the bromine atom addition reaction appear to be very similar for all PUFAs and have been determined to (1.2 +/- 0.3) x 10(9) M-1 s-1. Absolute rate constants in the order of 10(5)-10(6) s-1 have also been measured for the bromine atom elimination from various beta-bromoalkyl radicals. The results render bromine atoms a potential initiator for lipid peroxidation, and their reactions may well provide an important chemical basis for the overall toxic action of 1,2-dibromoethane and related substrates. PMID- 8342947 TI - Molluscan chymotrypsin-like protease: structure, localization, and substrate specificity. AB - A messenger RNA encoding a chymotrypsin-like preproprotease is expressed abundantly and specifically in the distal quarter of the intestine of the mollusc Haliotis rufescens (red abalone). Consistent with this finding, a chymotrypsin like activity was detected at highest concentration in the lumen of this segment of the intestine. Because the complexity of total protein in the distal intestinal fluid was low and the chymotrypsin-like protease was highly expressed, purification of the enzyme to near homogeneity was achieved by a single passage over an anion-exchange resin. The primary specificity of the protease, predicted from homology of the key amino acid residues (Ser189, Gly216, and Ser226) in the substrate binding site with similar residues lining the S1 subsites of other chymotrypsin-like enzymes, was confirmed by hydrolysis of a family of tetrapeptide substrates with different P1 amino acids. The optimal P1 residues include those with bulky, gamma-branched side chains (phenylalanine and leucine) similar to the side chain of the asparagine residue at P1 of the activation peptide of the proenzyme. Thus, unlike zymogens of the pancreatic serine proteases, which are activated by the common tryptic mechanism, the zymogen of the molluscan enzyme appears to be activated by an autocatalytic mechanism, i.e., by cleavage with active chymotrypsin-like protease. Additional unique properties of the enzyme predicted from the primary sequence include an unpaired cysteine, with the potential for internal thiol-disulfide isomerization between two different conformers of the protease. PMID- 8342948 TI - Further approaches to the quaternary structure of octopus hemocyanin: a model based on immunoelectron microscopy and image processing. AB - The direction of the polypeptide chains and the location of the functional units in Octopus vulgaris hemocyanin were studied by various methods. Monoclonal antibodies specific for the Ovc (clone Ov409) and Ovg (clone Ov315) functional units produced immunocomplex strings which were examined in the electron microscope. In both cases the immunocomplexes contained more than two hemocyanin molecules in their side view, demonstrating that in the whole hemocyanin neighboring polypeptide chains run in antiparallel directions. The interhemocyanin distances in the immunocomplexes also indicated that Ovg is located inside the cylinder, while Ovc is located in the external layers of functional units. In addition, the fact that the binding point of the Fab arm to the hemocyanin molecule was occasionally visible confirmed the external location of functional unit Ovc. Image processing of the whole hemocyanin cross-linked with dimethyl suberimidate showed that the end-on view is not a perfect cylinder but a regular pentahedron and that the five-arch collar is probably composed of five pairs of functional unit Ovg located inside the cylinder. The accessibility of cross-linked hemocyanin to functional unit-specific polyclonal antibodies, studied in immunoelectrophoresis, showed that Ovb and Ove are highly accessible, while Ovd, Ovf, and Ovg are not. The low accessibility of Ovd may be at least partially explained by its high sugar content which could hamper the accessibility of the antibody to the antigen. PMID- 8342949 TI - Hyperexpression of catalase in selenium-deprived murine L1210 cells. AB - Murine leukemia L1210 cells grown for 2-3 weeks in the presence of 1% serum without selenium supplementation [L.Se(-) cells] typically exhibited < 10% of the glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) activity of selenium-satisfied controls [L.Se(+) cells]. Concomitant with diminished GPX and PHGPX activity was a 1.5- to 2.0-fold increase in catalase (CAT) activity, which reverted to control levels when L.Se( ) cells were given sufficient Se for full expression of selenoperoxidase activity. Selenium manipulation affected total glutathione content similarly, but had no effect on glutathione-S-transferase or superoxide dismutase activity. Long term growth under Se-deficient conditions resulted in a progressive additional increase in CAT activity, which maximized after ca. 5 months. These cells [referred to as L'.Se(-)] attained CAT activity levels at least 100-times greater than those of Se-supplemented [L'.Se(+)] controls, whereas their glutathione content remained elevated by approximately 70%. Supplying L'.Se(-) cells with Se resulted in a rapid elevation to full GPX activity; however, CAT failed to decline in this case, suggesting that a selection for stable CAT hyperexpressing variants had been accomplished. Quantitative immunoblot analysis indicated that the high CAT activity of L'.Se(-) cells is accounted for by an elevated level of enzyme protein. Induction of CAT and selection for CAT-rich phenotypes, as apparent for Se-starved L1210 cells, was not observed in human K562 counterparts, which lack GPX and express only a low level of PHGPX. L.Se(-) cells were found to be more sensitive to H2O2-induced killing than L.Se(+) controls, whereas L'.Se(-) cells were exceedingly more resistant to H2O2 than L'.Se(+) counterparts. By contrast, L.Se(-) and L'.Se(-) cells were both more sensitive to t-butyl hydroperoxide than Se(+) controls, consistent with CAT being unimportant in the detoxification of this peroxide compared with GPX. This appears to be the first reported evidence for CAT hyperexpression in response to selenium deprivation. PMID- 8342950 TI - Kinetics of the "on-off" change in regulatory state of the muscle thin filament. AB - The excimer fluorescence of pyrene iodoacetamide-labeled tropomyosin bound to actin is a probe of the regulatory state change of the muscle thin filament associated with the cooperative binding of myosin subfragment 1 (S1) (Y. Ishii and S. S. Lehrer, Biochemistry 29, 1160, 1990). In this study, the excimer fluorescence was used to monitor the kinetics of the "on-off" state change due to the ATP-induced dissociation of S1 from actin-tropomyosin. A lag in the fluorescence change indicated that the thin filament was maintained in the "on state" until more than half of the S1s dissociate. The on-off transition rate was slower than the dissociation of the remaining S1s. These delays in relaxation to the "off-state" may explain some observed kinetic and cooperative effects during tension measurements. PMID- 8342952 TI - Dissociation of relaxation and myosin light chain dephosphorylation in porcine uterine muscle. PMID- 8342951 TI - cDNA cloning and expression of a soluble epoxide hydrolase from human liver. AB - We report the cloning and expression of a cDNA that encodes a soluble epoxide hydrolase from human liver. The 2101-base clone predicts a 554-residue protein (M(r) 62,640) with an apparently imperfect peroxisomal targeting signal of Ser Lys-Met at the carboxy terminus. The cDNA was expressed in the baculovirus system in the Spodoptera frugiperda 21 cell line. The recombinant protein was similar to soluble epoxide hydrolase isolated from human liver in terms of molecular weight, hydrolytic activity, inhibition, and immunoreactivity. PMID- 8342953 TI - Plant dnaj homologue: molecular cloning, bacterial expression, and expression analysis in tissues of cucumber seedlings. AB - Proteins homologous to the bacterial dnaJ protein have been implicated as molecular chaperones in different compartments of eukaryotes. A plant equivalent is now described in various cucumber tissues. Using a cDNA library constructed from poly(A)-rich RNA of cotyledons of etiolated seedlings and dnaJ-specific probes, we isolated clones encoding full-length cDNAs: clone CSDNAJ-1 contained a 1.7-kb insert with a single open reading frame of 413 amino acid residues encoding a protein of M(r) 46, 012; pCSDNAJ-2 differed from pCSDNAJ-1 by an additional nucleotide and predicted a protein of M(r) 26, 104. Peptides of similar sizes were observed when the cDNA information was expressed by in vitro transcription and translation or expressed in vivo in bacteria. Using mRNA isolated by hybrid selection for in vitro translation we observed the formation of CSDNAJ-1 protein. Comparisons revealed that the similarity in primary structure between CSDNAJ-1 protein and dnaJ homologues in eukaryotes is most pronounced in the N-terminal region. The high degree of identity (39%) of CSDNAJ 1 protein with the yeast dnaJ homologue YDJ1 protein suggests that csdnaJ proteins assist intracellular protein transfer. The predicted CSDNAJ-1 protein is characterized by a fourfold repetition of the motif CXXCXGX(G) and by a C terminus -QCAQQ. Analysis of gene expression at the level of mRNA showed that the putative dnaJ protein is expressed in cucumber seedlings in all tissues, but exceedingly high in hypocotyledons and roots. The level of dnaJ mRNA was transiently increased by a factor of 1.5-2.0 when heat shock was applied to the seedlings. PMID- 8342954 TI - Hepatic effects of endothelin: metabolism of [125I]endothelin-1 by liver-derived cells. AB - Endothelin, a potent vasoactive peptide originally isolated from cultured porcine endothelial cells, (1) elicits hemodynamic and glycogenolytic actions in perfused rat liver; (2) evokes phosphoinositide signaling in hepatic cells; and (3) stimulates synthesis of mediators in Kupffer cells and glucose production in hepatocytes. Recently, we characterized receptor(s) for endothelin on hepatocytes (C. R. Gandhi, R. H. Behal, S. A. K. Harvey, T. Nouchi, and M. S. Olson, Biochem. J. 287, 897-904, 1992). Both hepatocytes and Kupffer cells rapidly internalize [125I]endothelin-1 ([125I]ET-1). In the present study we exposed primary cultures of hepatocytes or Kupffer cells to [125I]ET-1 and analyzed the radiolabeled metabolites which appeared in the cell medium. Six metabolites were separated by high-performance liquid chromatography (HPLC) from hepatocyte medium; these peaks had approximate elution times of 5 (free iodide), 22, 35, 37, 38, and 41 min, respectively, whereas the elution time for [125I]ET-1 was 43 min. The kinetics of formation of the metabolites, and experiments using excess unlabeled ET-1, both showed that internalization of the native peptide by hepatocytes is required for the metabolism of [125I]ET-1 into metabolite, and for the subsequent deiodination of metabolite. The formation of metabolites does not require internalization of the native peptide. In Kupffer cells, the cell medium contained only metabolite and metabolite. Internalization of the native peptide was required for the formation of metabolite but not for metabolite. Three classes of [125I]ET-1 metabolites from hepatic cells also were separated by sequential precipitation with trichloroacetic acid (TCA) and with silver nitrate. This procedure facilitated multiple rapid assays of [125I]ET-1 metabolism. Phosphoramidon, an inhibitor of neutral metalloendopeptidases, did not affect significantly the binding or the metabolism of [125I]ET-1 by hepatocytes or Kupffer cells. The aminopeptidase inhibitor bacitracin strongly attenuated [125I]ET-1 metabolism by hepatocytes, with a concomitant increase in the intracellular content of [125I]ET 1. These data suggest that enzymes capable of endothelin degradation are present both on the surface and in the intracellular compartment of hepatic cells, and that endothelin is not metabolized by neutral endopeptidase 24.11 in the liver. PMID- 8342955 TI - Isolation and properties of YCK2, a Saccharomyces cerevisiae homolog of casein kinase-1. AB - A soluble fragment of YCK2, a casein kinase-1 isoform from Saccharomyces cerevisiae, has been purified and characterized in vitro. The procedure enriches enzyme activity to a final specific activity of 4.7 mumol min-1 mg-1 (when assayed with casein as substrate). Structural analysis reveals that the preparation arises from N-terminal modification and C-terminal proteolysis of the initially synthesized 546-residue protein, consisting of residues 2-495 +/- 1. Kinetic analysis demonstrates that YCK2 is similar to casein kinase-1 isolated from other organisms in its inability to use GTP as nucleotide substrate, in its sensitivity to heparin and ribofuranosyl-benzimidazole inhibitors, and in its peptide substrate selectivity. The enzyme is unusual, however, in that it is insensitive to the potent mammalian casein kinase-1 inhibitor N-(2-aminoethyl)-5 chloroisoquinoline-8-sulfonamide. PMID- 8342956 TI - Accumulation of intermediates and isotopically sensitive enolization distinguish between aromatase (cytochrome P450 CYP19) from rat ovary and human placenta. AB - Aromatase activity in microsomes from human placenta (HPM) and rat ovary (ROM) was compared by measuring the accumulation of 19-oxygenated intermediates, the effect of tritium substitution upon rates, and the distribution of tritium in products. A considerable accumulation of intermediates (19-hydroxyandrogen and 19 al-androgen) and a lag in product formation (estrogen and water) was observed with ROM but not HPM. Addition of purified NADPH-cytochrome P450 reductase to ROM decreased the accumulation of 19-hydroxyandrostenedione and increased the rate of estrone formation. This difference could not be attributed to the microsomal reductase concentration since its concentration was similar in both tissues. Estrogen formation by aromatase from these tissues was not associated with a significant kinetic isotope effect when androstenedione was labeled with tritium at C-1 and C-2. Isotopically sensitive switching (branching) from the 19-al androstenedione enzyme complex to form free 19-al-androstenedione rather than estrogen was not observed. These data suggest that for aromatase in both tissues, an enzymatic step exists between the 19-al-androstenedione intermediate and hydrogen abstraction or enolization that has a large commitment to catalysis. The distribution of tritium into the products, water and estrogen, was dependent upon substrate, enzyme source, and position of the label. Incubation of 1 beta, 2 beta [3H]androstenedione and testosterone with ROM and 1 beta,2 beta-[3H]testosterone with HPM resulted in approximately 50% of the label being retained in the estrogen and 50% being lost in water. The majority of the label was lost in water upon incubation of 1 beta-labeled substrates with microsomes from both sources. Unexpectedly, no label was lost to water upon incubation of the specifically 1 alpha,2 alpha-labeled substrates with either enzyme source. Only incubation of 1 beta,2 beta-[3H]androstenedione with HPM resulted in loss of tritium from the 2 position. These data were interpreted to indicate that, for androstenedione metabolism by ROM and testosterone metabolism by both ROM and HPM, enolization occurs nonspecifically in an isotopically sensitive manner following deformylation, but for HPM metabolism of androstenedione enolization occurs in an enzyme-assisted manner. The studies show that aromatase located in ROM differs from that in HPM by its accumulation of intermediates and inability to selectively remove the 2 beta-tritium from androstenedione. PMID- 8342957 TI - Differential solubilization of membrane lipids by detergents: coenrichment of the sheep brain serotonin 5-HT1A receptor with phospholipids containing predominantly saturated fatty acids. AB - Most membrane receptors lose binding activity during purification and we studied the correlation between this event and differential solubilization of membrane lipids by detergents. Both 3-[(3-cholamidopropyl)dimethylammonio]-1 propanesulfonate [Chaps; high critical micellar concentration (cmc) approximately 0.5%] and n-dodecyl beta-D-maltoside (DDM; low cmc approximately 0.009%) solubilized the 8-[3H]hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) binding serotonin 5-HT1A receptor (5-HT1A-R) optimally at 2% (w/v) detergent concentration despite the widely differing cmc of the two detergents. In contrast, n-octyl-beta-D-glucopyranoside (octyl glucoside; high cmc approximately 0.7%), Thesit (low cmc approximately 0.005%), and Triton X-100 (low cmc approximately 0.013%) solubilized virtually no [3H]8-OH-DPAT-binding activity. The total mass of solubilized lipids was always low at 0.5% detergent concentration and attained a plateau between 1 and 2.5% for all detergents except octyl glucoside. The mass of octyl glucoside-solubilized lipids showed an increasing trend even at 3.0% detergent concentration. The total amount of solubilized lipid is unrelated to the amount of 5-HT1A-R solubilized but the species of lipid is important. Thus Chaps and DDM, with diverse structures and cmc, both preferentially solubilized phospholipids enriched in saturated fatty acids (67 and 72%, respectively). In contrast, octyl glucoside, Triton X-100, and Thesit showed no preference in solubilizing phospholipids. Octyl glucoside, which solubilized significantly higher proportions of saturated fatty-acid-containing phosphatidylethanolamine (slightly higher saturated fatty acids in total phospholipids), also produced more (twofold higher) solubilized 5-HT1A sites than Triton X-100 and Thesit. This suggests an optimum involvement of saturated fatty acid side chains in forming tightly packed vesicles which stabilize the 5-HT1A-R more than the vesicles of higher fluidity formed by phospholipids containing higher proportions of cis-double-bonded unsaturated fatty acids. Indeed, delipidation of the 1.5% Chaps-solubilized receptor preparations by Sephacryl S 200 column chromatography eliminated essentially all [3H]8-OH-DPAT-binding activity. Therefore, for efficient recovery during solubilization and reconstitution of a prototypic heptahelical receptor (5-HT1A), it is essential to stabilize the receptor protein through association with saturated phospholipids. PMID- 8342958 TI - Protein-lipid interactions of the proteolipid c subunit of the Escherichia coli proton-translocating adenosinetriphosphatase. AB - Interactions between Escherichia coli membrane phospholipids and the hydrophobic c subunit of the F1F0 proton-translocating ATPase were characterized. Extraction of E. coli membranes with a neutral mixture of chloroform and methanol and subsequent separation steps produced several protein-containing fractions. The protein-containing fraction most soluble in organic solvents contained subunit c and a lipid fraction enriched in phosphatidylglycerol compared to total E. coli membrane phospholipids. Other ATPase subunits and some additional proteins extracted from the membranes by this procedure could be separated from the c subunit by subsequent extraction. The purified and delipidated c subunit contained fatty acids which were released upon treatment with boron trifluoride methanol. Furthermore, deleting and restoring the genes for the F0 subunits changed the composition of extractable membrane phospholipid and fatty acids, indicating that the F0 plays a significant structural role in the membrane. PMID- 8342959 TI - Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS 30D hepatoma mitochondria. AB - Mitochondria isolated from normal rat liver and AS-30D hepatoma were concurrently evaluated with regard to their bioenergetic and metabolic properties. AS-30D mitochondria oxidized many NAD-linked respiratory substrates at rates 1.5-4 times faster than those from liver, a fact which contributes to their diminished membrane depolarization on conversion from state 4 to state 3 respiration. AS-30D mitochondria exhibited no signs of a "truncated" Krebs cycle, nor did they oxidize malate preferentially based upon its origin in the cytosol or the mitochondrial matrix. In addition, beta-oxidation in AS-30D mitochondria was not sufficient to suppress respiratory CO2 production and induce pyruvate carboxylation to the extent observed in liver. Finally, AS-30D mitochondria were able to oxidize externally generated NADH in a reconstituted system, but in a manner independent of the transmembrane electrical potential (delta psi), suggesting that the malate-aspartate shuttle is not operable in vivo. This fact may necessitate the adaptations tumor cells make to reoxidize cytosolic NADH through glycolysis even in the presence of adequate oxygen. PMID- 8342960 TI - Skin-homing T lymphocytes: detection of cutaneous lymphocyte-associated antigen (CLA) by HECA-452 in normal human skin. AB - The immigration of circulating T cells into specific tissues is directed by the interaction between adhesion molecules on lymphocyte subpopulations and their ligands on vascular endothelium. Of these, endothelial leucocyte adhesion molecule (ELAM-1), weakly expressed in normal human skin (NHS), seems to be the counter-structure for cutaneous lymphocyte-associated antigen (CLA). CLA is a 200 kDa cell-surface glycoprotein of which the sugar moieties sialyl Le(a) and sialyl Le(x) are the possible epitopes recognized by the monoclonal antibody HECA-452. HECA-452 was originally described as a marker for lymphoid organ high endothelial cells, but 16% of peripheral-blood-derived T cells react with this antibody. We studied the expression of CLA on the cellular constituents of the skin immune system (SIS). By applying immunohistochemical double staining, 41% of CD3+ T cells, 44% of CD4+ T cells and 31% of CD8+ T cells were found to express CLA. Keratinocytes, CD1a+ Langerhans cells (LC) and endothelial cells did not express HECA-452 in significant numbers in NHS. Monocytes were found to express HECA-452 in 14% of CD68+ cells. CLA expression was present on a relatively low percentage of T cells and subsets localized distant from NHS vessels, suggesting loss of the molecule during further migration after transendothelial passage. However, intraepidermal T cells expressed CLA in similar percentages to T cells localized directly perivascularly. Our findings support the notion that CLA expression by T cells is associated with their homing into cutaneous structures. PMID- 8342961 TI - Mast cell tryptase and chymase in developing and mature psoriatic lesions. AB - The number and distribution of mast cells in non-lesional and lesional skin samples from 13 psoriatic patients were analyzed enzyme- and immunohistochemically. Mast cell tryptase was stained with the sensitive substrate Z-Gly-Pro-Arg-4-methoxy-2-naphthylamide, and chymase with Suc-Val-Pro Phe-MNA and monoclonal B7 anti-chymase antibody. In addition, healthy-looking skin from 27 psoriatic patients was tape-stripped resulting in induction of the Kobner response in 9 patients. Sequential biopsies were taken before and after (7, 14 and 21 days) tape-stripping, and both tryptase and chymase were stained enzyme-histochemically. In non-lesional psoriatic skin, 70 +/- 24% (mean +/- SD) of the mast cells contained chymase enzyme activity, and 78 +/- 18% chymase immunoreactivity. About 10% of the chymase-immunoreactive cells lacked chymase activity. In lesional psoriatic skin, tryptase-positive cells were increased in number throughout the dermis but especially beneath the epidermis. Chymase immunoreactivity paralleled the tryptase activity, whereas chymase activity was strongly diminished both in terms of mast cell numbers and in staining intensity in the papillary dermis. The apparent inactivation of chymase may be due to the action of the chymase inhibitors, alpha 1-antitrypsin and alpha 1 antichymotrypsin, localized immunohistochemically in mast cells of lesional and non-lesional psoriatic skin. In the developing psoriatic lesion, mast cells displaying chymase activity were already 27-38% decreased in number in the upper dermis on day 7 after tape-stripping, along with the first clinical signs of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8342962 TI - The herpes-specific immune response of individuals with herpes-associated erythema multiforme compared with that of individuals with recurrent herpes labialis. AB - Infection with herpes simplex virus (HSV) is the most common precipitating factor in the development of erythema multiforme (EM). It is not known why only a few of the many individuals who experience recurrent HSV infection also develop herpes associated EM (HAEM), although a difference in the HSV-specific immune response has been postulated. The purpose of this study was to compare the HSV-specific immune response of individuals with HSV infection alone with that of individuals with HAEM. There were 21 patients in each of the two groups. Four parameters of the HSV-specific immune response were examined: (1) anti-HSV IgG titers were measured by ELISA; (2) antibody neutralization was assessed using a plaque assay; and (3) antibody-dependent complement-mediated cytotoxicity, and (4) antibody dependent cellular cytotoxicity were investigated using a previously described in vitro HSV-specific cytotoxicity assay. No statistically significant differences were detected between the two patient groups. Thus, a difference in these HSV specific immune mechanisms does not explain the development of HAEM in some individuals with recurrent HSV infection. PMID- 8342963 TI - Epidermis reconstructed from the outer root sheath of human hair follicle. Effect of retinoic acid. AB - In the present paper, we show that a multilayered and well-differentiated epidermis can easily and rapidly be generated in vitro from the outer root sheath of human hair follicles deposited on de-epidermized demis. Histologically, this epidermis presented characteristic features of normal human epidermis in vivo. Moreover, markers specific for interfollicular keratinocyte terminal differentiation, such as the K10 keratin, involucrin, membrane-bound transglutaminase, filaggrin and loricrin, were expressed in the reconstructed tissue. By in situ hybridization, keratin K5 and K10 mRNAs were detected in the basal and suprabasal cells, respectively, as in normal human epidermis. The differentiation pattern achieved in this reconstructed epidermis confirms the already reported phenotypical shift from outer root sheath cells to interfollicular keratinocytes and shows that this transition takes place in the absence of living fibroblasts. The differentiation of the reconstructed epidermis thus obtained was modulated by retinoic acid in a dose-dependent manner. This culture system on dead dermis is easier to handle than similar cultures on collagen-fibroblast lattices because of the resistance of dermis to mechanical forces and to collagenolysis. It could represent a valuable wound-healing model and a promising tool for pharmacological studies on in vitro reconstructed skin. PMID- 8342964 TI - Soluble factors from human hair papilla cells and dermal fibroblasts dramatically increase the clonal growth of outer root sheath cells. AB - Depending on environmental influences, follicular outer root sheath (ORS) cells in vivo can differentiate either towards interfollicular keratinocytes or, as demonstrated in the rat vibrissa, hair matrix cells. Crucial regulators of both their proliferation and differentiation are the mesenchymal cells of the respective tissues. The interactions of human ORS cells with human hair papilla cells (HPC) or human dermal fibroblasts (HDF) were studied using a two-chamber model separating the two cell types either by a microporous membrane or additionally by a medium layer. The results of 3H-thymidine incorporation studies indicated that ORS cell growth was markedly enhanced in co-culture with either HPC or HDF, the highest stimulatory effect resulting when ORS cells were in close association with the mesenchymal cells. No correlation was found between ORS cell proliferation and IL-6 production in the co-culture system, thus pointing to the secretion by HPC and HDF of growth-promoting soluble factors that are different form IL-6 as well as from EGF, bFGF and insulin present in the culture medium. PMID- 8342965 TI - Modified epidermal lipid composition in air-exposed culture of non-bullous congenital ichthyotic erythroderma (NBCIE) keratinocytes. AB - Emerged epidermal cultures on dead de-epidermized dermis (DED) constitute an excellent model for in vitro reproduction of dermatoses linked to a keratinocyte defect. We used such cultures for studies of non-bullous congenital ichthyotic erythroderma (NBCIE). Keratinocytes of normal and pathological origin were expanded in submerged cell cultures and frozen keratinocytes from the resulting cell bank were subsequently used for seeding on DED. Lipid extracts from 14 day emerged cell cultures were assayed qualitatively and quantitatively using thin layer chromatography and compared with the neutral and non-polar lipid profiles obtained from normal epidermis extracts and with those from the plantar stratum corneum of healthy donors and untreated NBCIE patients. The ichthyotic cultures were found to contain significantly elevated levels of n-alkanes, as were the lipid extracts from the patients' plantar horny layer. Our results demonstrate that a major marker of the NBCIE epidermis can be reproduced under the emerged culture conditions. They also indicate that the characteristic n-alkane increase in NBCIE is indeed endogenous and not merely related to possible contamination from topical treatments. PMID- 8342966 TI - Antibody titers to an oxidized thymidine moiety are altered by systemic pharmacotherapy and by ultraviolet B phototherapy. PMID- 8342967 TI - EGF induces ornithine decarboxylase transcription in Balb/MK keratinocytes: a proposed mechanism for the TGF alpha autocrine loop. PMID- 8342968 TI - Quantitative evaluation of urea in stratum corneum of human skin. PMID- 8342969 TI - [The physician and the interview]. PMID- 8342970 TI - [Transcatheter arterial embolization in the hemorrhagic complications of kidney trauma]. AB - Transcatheter arterial embolization is a nonsurgical alternative for the complications arising from biopsy, surgery and blunt or penetrating renal trauma. Fourteen transcatheter embolization procedures were performed in 13 patients for hemorrhage following biopsy of the native kidney (3 cases) biopsy of the transplanted kidney graft (3 cases), stone surgery (3 cases), blunt abdominal trauma (2 cases), a stab wound (1 case) and an A-V fistula (1 case). The bleeding was effectively controlled in all cases. Nephrectomy was required in 3 cases (21.4%) whose kidneys were not viable and cannot be ascribed to a complication of the embolization procedure. The diagnostic aspects of hemorrhage arising from renal trauma, the embolization technique and its indications are discussed. In our view, transcatheter arterial embolization is the technique of choice for the hemorrhagic complications of blunt or penetrating renal trauma or those caused by biopsy or surgery. PMID- 8342971 TI - [Renal angiomyolipoma. Our case histories]. AB - We reviewed the cases of angiomyolipoma that had been diagnosed and treated in our urology services from 1978 to 1991. The study showed a higher incidence in the females; it frequently presented as a solitary tumor; a high specificity was found for the US (hyperechoic mass) and CT (areas of low attenuation ratio) findings. Owing to these diagnostic techniques, conventional surgery is no longer the only treatment. Embolization is considered to be the first therapeutic approach. PMID- 8342972 TI - [A prospective and randomized study of the complete response, index of recurrences and progression in superficial bladder carcinoma treated with mitomycin C alone versus mitomycin C and BCG alternatively]. AB - The results of a comparative randomized study on intravesical chemoprophylaxis are presented. The study comprised 66 patients; one group of 29 patients received mitomycin C alone, while another group of 37 patients received mitomycin C and alternating BCG therapy. This latter treatment modality was found to achieve a slightly higher complete response rate and a much lower tumor progression rate. Although these results were not statistically significant (p > 0.05), they indicate that if the study were comprised of a larger series, the combined modality may be shown to achieve better results than the other modalities currently used. PMID- 8342973 TI - [The usefulness of computerized axial tomography (CT) in establishing the composition of calculi]. AB - Determining stone composition before extracorporeal lithotripsy can be potentially useful. A total of 90 calculi of 6 different chemical composition (calcium oxalate monohydrate, calcium oxalate dihydrate, magnesium ammonium phosphate, phosphate carbonate, uric acid and phosphate oxalate) were analyzed in vitro using computed tomography (CT). The mean, central, peripheral, maximum, minimum stone density and stone morphology were determined. At least in vitro, the serial analyses of the mean, minimum, central stone density and stone morphology permitted distinguishing these 6 types of calculi, although 53% of the calcium oxalate dihydrate calculi could not be distinguished from the phosphate oxalate stones. PMID- 8342974 TI - [The usefulness of dual-energy radiographic densitometry (DO) in establishing the composition of calculi]. AB - Dual-energy radiographic bone densitometry is utilized to determine the bone mineral content in patients with osteoporosis. The present in vitro experimental study investigated the usefulness of densitometry in determining stone composition and in evaluating the mineral and non mineral phases of the calculus. For the study we analyzed 114 calculi of 6 different chemical composition (calcium oxalate monohydrate, calcium oxalate dihydrate, magnesium ammonium phosphate, phosphate carbonate, uric acid and phosphate oxalate). The phosphate carbonate calculi had the highest mineral density, whereas the uric acid calculi had the lowest and contained more water. Although densitometry appears to be of little value in determining stone composition, it provides information on the mineral and non mineral phases of the calculus. PMID- 8342975 TI - [The therapeutic approach in vascular damage from pyelocaliceal endoscopic urology]. AB - Six cases of vascular lesion associated with percutaneous removal of renal calculi are described. The lesions had been caused during percutaneous access or ultrasound fragmentation of the stone. Those that had resolved spontaneously have not been included. When vascular injury is suspected during the procedure, the appropriate measures must be taken to resolve the different complications, such as arteriovenous, arteriocaliceal or venocaliceal fistula. Since there is little reference to this subject in the Spanish literature, the experience described herein may be of interest to the urologist who has only recently begun to perform this technique. PMID- 8342976 TI - [Ureteroscopy. Our results and complications]. AB - From November, 1987 to December, 1990, 399 cases of ureteral calculi were treated by rigid ureteroscopy (URS). Our success and complication rates are presented. Of these, 99 (25%) had a calculus in the pelvis (78/99), iliac (15/99) or lumbar (6/99) ureter, and 300 (75%) had Sandstrasse in the distal ureter. The cases with Sandstrasse were submitted to ureteroscopy within the first 48-72 hours to remove the ureteral obstruction, prevent hydronephrosis or sepsis and to expedite treatment. If symptomatic, obstructive and/or 7 mm or more in diameter, a nephrostomy tube was placed first whenever there was sepsis [23/300 (7%) of those with Sandstrasse and 3/99 (3%) of those with a ureteral calculus] or marked dilatation of the renal cavities [29/300 (9%) and 6/99 (6%), respectively]. The success rate was 93% for the cases with Sandstrasse versus 85% for those with a ureteral calculus, and the complication rates were 5.7% versus 9%, respectively. The foregoing results confirm the high success rate and scant morbidity of ureteroscopy in the treatment of ureteral calculus and Sandstrasse. PMID- 8342977 TI - [The percutaneous management of stenosis in uretero-intestinal diversions]. AB - Five patients with a stenotic uretero-intestinal diversion were submitted to percutaneous balloon dilatation. The stricture was successfully dilated without complications in all cases. One case, however, required another dilatation procedure due to restenosis 30 days later. The low cost, short hospital stay, absence of important complications and low recurrence rate make percutaneous balloon dilatation the procedure of choice in these patients. PMID- 8342978 TI - [Primary choriocarcinoma of the bladder. A case report with immunohistochemical and ultrastructural study]. AB - Some tumors frequently encountered in other organs and usually with a high grade of malignancy and a poor prognosis have been recently described in the urinary bladder, very often in close relationship with a pre-existing transitional cell carcinoma. Of these, primary choriocarcinoma of the urinary bladder is one of the most uncommon and its histogenesis much discussed. It is important to identify this tumor type, since a change in the oncologic treatment may be warranted. We report an additional case of this rare bladder tumor with clinicopathologic study and discuss the histogenetic and therapeutic aspects. PMID- 8342979 TI - [The infected solitary renal cyst. A case review and review of the literature]. AB - A case of solitary infected renal cyst is presented. The clinical features, diagnosis and treatment of this disease entity are discussed and the literature reviewed. Less than thirty cases have been reported until the last decade. PMID- 8342980 TI - [Renal-cell adenocarcinoma and massive retroperitoneal hemorrhage during pregnancy]. AB - We report a case of renal cell carcinoma that had manifested as massive retroperitoneal hemorrhage in the second trimester of pregnancy. The diagnosis was made on the basis of the clinical and ultrasound findings. The patient was submitted to unilateral nephrectomy at 27 wk of gestation and she delivered by cesarean section at 35 wk gestation. Both mother and infant are well 1 year postoperatively. PMID- 8342981 TI - [Hematuria due to polypoid cystitis. Its differential diagnosis from bladder carcinoma]. AB - Polypoid cystitis is not uncommon in patients with a permanent urethral catheter. In some cases difficulties are encountered when making the differential or anatomopathological diagnosis from transitional cell carcinoma of the bladder. We report a case of polypoid cystitis mimicking bladder carcinoma in a patient with a permanent urethral catheter. PMID- 8342982 TI - [The cutaneous metastasis of prostatic adenocarcinoma. Apropos a case]. AB - An additional case of prostatic adenocarcinoma metastasizing to the skin is described. The metastatic lesions appeared late and despite surgical and hormonal castration. To our knowledge only 5 cases have been reported in the Spanish literature. Cutaneous metastasis originating from adenocarcinoma of the prostate is a sign of poor prognosis and patients die within 6 months after the appearance of the metastatic lesions. The site and route of tumor dissemination in the present case coincide with those reported in the literature. PMID- 8342983 TI - [A xanthogranulomatous psoas abscess 4 years after nephrectomy for xanthogranulomatous pyelonephritis]. AB - We report a case of xanthogranulomatous abscess of the left psoas muscle in a patient who underwent nephrectomy for xanthogranulomatous pyelonephritis four years earlier. Pathogens unlike those usually found in this type of inflammatory reaction were grown on culture. The possible relationship between the two infectious disease processes is analyzed. PMID- 8342984 TI - [A chronic intrascrotal inflammation secondary to free foreign bodies in the tunica vaginalis]. AB - We report a case of granulomatous reaction to intrascrotal foreign body (vegetable fibers) that presented as an inguinal mass in a patient who had been treated for perforation of the jejunum loop incarcerated in inguinal hernia. To our knowledge a similar case has not been reported in the literature. PMID- 8342985 TI - [Adenocarcinoma in addition to bladder exstrophy. Apropos a case and a review of the literature]. AB - Herein we describe a case of adenocarcinoma complicating exstrophy of the bladder in a 59-year-old patient. The morphologic, histochemical and immunohistochemical analyses revealed a colonic glandular adenocarcinoma. The two hypotheses relative to its pathogenesis are briefly discussed. To date, 106 cases have been reported in the literature. PMID- 8342986 TI - [The recent appearance of the journal Current Opinion in Urology]. PMID- 8342987 TI - The electromechanical impactor: a new device for intracorporeal stone fragmentation. AB - The Electromechanical Impactor was conceived as a safe and effective device for intracorporeal stone fragmentation. It is a 3 French EHL electrode enclosed within a stainless steel sheath. The interior is irrigated with saline. Discharge of the system causes an EHL spark which vaporizes saline and produces a cavitation bubble and subsequent shock wave. The shock wave propels a conical titanium tip forward for a distance of 2.7 mm with an impact pressure of 900 bar. Bench and animal testing has proven its effectiveness for stone fragmentation and safety for use within the ureter. The mean lifetime of each probe is approximately 700 pulses. It is used under direct vision through the straight operating port of a rigid or semi-rigid 9.5 French ureteroscope. Clinical studies at the Massachusetts General Hospital (reported herein) and the Mayo Clinic demonstrate approximately 90% efficacy. It is especially effective on cystine, calcium oxalate dihydrate, struvite and mixed calcium oxalate monohydrate calculi. Shiny-smooth black calcium oxalate monohydrate calculi will fragment but are more resistant. There has been no evidence of ureteral wall injury. The EMI is currently 5 French and is used both safely and effectively under direct vision of fragment ureteral calculi. Larger sizes are designed for percutaneous use and for bladder stone fragmentation. PMID- 8342988 TI - Primary benign vesical teratoma. A case report. AB - Primary benign vesical teratomas are rare. Most of the cases reported are paravesical teratomas rupturing into the bladder. A case of primary benign vesical teratoma suspected preoperatively and later confirmed at histopathology is reported. PMID- 8342989 TI - The elusive pathophysiology of the multiple organ failure syndrome. PMID- 8342990 TI - The gastrointestinal tract. The "undrained abscess" of multiple organ failure. AB - OBJECTIVE: This study determined the association between proximal gastrointestinal (GI) colonization and the development of intensive care unit (ICU)-acquired infection and multiple organ failure (MOF) in a population of critically ill surgical patients. SUMMARY BACKGROUND DATA: ICU-acquired infection in association with progressive organ system dysfunction is an important cause of morbidity and mortality in critical surgical illness. Oropharyngeal and gastric colonization with the characteristic infecting species is common, but its association with ICU morbidity is poorly defined. METHODS: A prospective cohort study of 41 surgical ICU patients was undertaken. Specimens of gastric and upper small bowel fluid were obtained for quantitative culture; the severity of organ dysfunction was quantitated by a numeric score. RESULTS: One or more episodes of ICU-acquired infection developed in 33 patients and involved at least one organism concomitantly cultured from the upper GI tract in all but 3. The most common organisms causing ICU-acquired infection--Candida, Streptococcus faecalis, Pseudomonas, and coagulase-negative Staphylococci--were also the most common species colonizing the proximal GI tract. Gut colonization correlated with the development of invasive infection within 1 week of culture for Pseudomonas (90% vs. 13% in noncolonized patients, p < 0.0001) or Staphylococcus epidermidis (80% vs. 6%, p < 0.0001); a weaker association was seen for colonization with Candida. Infections associated with GI colonization included pneumonia (16 patients), wound infection (12 patients), urinary tract infection (11 patients), recurrent (tertiary) peritonitis (11 patients), and bacteremia (10 patients). ICU mortality was greater for patients colonized with Pseudomonas (70% vs. 26%, p = 0.03); organ dysfunction was most marked in patients colonized with one or more of the following: Candida, Pseudomonas, or S. epidermidis. CONCLUSIONS: The upper GI tract is an important reservoir of the organisms causing ICU-acquired infection. Pathologic GI colonization is associated with the development of MOF in the critically ill surgical patient. PMID- 8342991 TI - Hepatocyte injury by activated neutrophils in vitro is mediated by proteases. AB - OBJECTIVE: This study determined the mechanism used by neutrophils (PMNs) to induce hepatocellular injury. SUMMARY BACKGROUND DATA: Neutrophils have been shown to be potent mediators of cell and tissue injury and have been hypothesized to contribute to the hepatic injury that occurs after trauma and infection. Oxygen radical scavengers protect the liver in vivo from inflammatory injury and it has been suggested that PMNs are the source of these toxic oxygen radicals. The specific mechanism used by PMNs to produce hepatocellular damage, however, has not been determined. METHODS: Neutrophils were cultured in vitro with hepatocytes (HCs) and stimulated with phorbol 12-myristate 13-acetate (PMA) to induce HC injury in the presence of oxygen radical scavengers and protease inhibitors. RESULTS: PMA induced a PMN-mediated HC injury that was dependent on the number of PMNs present and the concentration of PMA. Protease inhibitors reduced the extent of HC injury, while oxygen radical scavengers had no effect. Hydrogen peroxide, directly applied, was able to injure HCs, but only at concentrations greater than those that could be produced by PMA-stimulated PMNs. CONCLUSIONS: PMNs are cytotoxic to cultured HCs, predominantly due to the release of proteolytic enzymes, while HCs appear relatively resistant to oxidative injury. Involvement of neutrophil toxic oxygen radicals in hepatic damage in vivo may require impairment of HC antioxidant defenses or may involve injury to nonparenchymal liver cells with secondary effects on HCs. PMID- 8342992 TI - Open cholecystectomy. A contemporary analysis of 42,474 patients. AB - OBJECTIVE: This study evaluated, in a large, heterogeneous population, the outcome of open cholecystectomy as it is currently practiced. SUMMARY BACKGROUND AND DATA: Although cholecystectomy has been the gold standard of treatment for cholelithiasis for more than 100 years, it has recently been challenged by the introduction of several new modalities including laparoscopic cholecystectomy. Efforts to define the role of these alternative treatments have been hampered by the lack of contemporary data regarding open cholecystectomy. METHODS: A population-based study was performed examining all open cholecystectomies performed by surgeons in an eastern and western state during a recent 12-month period. Data compiled consisted of a computerized analysis of Uniformed Billing (UB-82) discharge analysis information from all non-Veterans Administration (VA), acute care hospitals in California (Office of Statewide Planning and Development [OSHPD]) and in Maryland (Health Services Cost Review Commission [HSCRC]) between January 1, 1989, and December 31, 1989. This data base was supplemented with a 5% random sample of Medicare UB-82 data from patients who were discharged between October 1, 1988, and September 30, 1989. Patients undergoing cholecystectomy were identified based on diagnosis-related groups (DRG-197 and DRG-198), and then classified by Principal Diagnosis and divided into three clinically homogeneous subgroups: acute cholecystitis, chronic cholecystitis, and complicated cholecystitis. RESULTS: A total of 42,474 patients were analyzed, which represents approximately 8% of all patients undergoing cholecystectomy in the United States in any recent 12-month period. The overall mortality rate was 0.17% and the incidence rate of bile duct injuries was approximately 0.2%. The mortality rate was 0.03% in patients younger than 65 years of age and 0.5% in those older than 65 years of age. Mortality rate, length of hospital stay, and charges were all significantly correlated (p < 0.001) with age, admission status (elective, urgent, or emergent), and disease status. CONCLUSIONS: These data indicate that open cholecystectomy currently is a very safe, effective treatment for cholelithiasis and is being performed with near zero mortality. The ultimate role of laparoscopic cholecystectomy needs to be defined in the context of current and contemporary data regarding open cholecystectomy. PMID- 8342993 TI - A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. AB - OBJECTIVE: This study determined, prospectively, whether duodenotomy (DX) should be routinely performed in explorations for patients with Zollinger-Ellison syndrome (ZES). SUMMARY BACKGROUND DATA: Duodenal gastrinomas are now being found with increasing frequency in patients with Zollinger-Ellison syndrome. The surgical approach used to detect these tumors is controversial. Some recommend intraoperative endoscopy with transillumination (IOE) at surgery, while others recommend routine DX. METHODS: Beginning in 1989, the authors prospectively compared the ability of palpation, intraoperative ultrasound (IOUS), IOE, and DX (in that sequence) to detect gastrinomas in 35 consecutive patients with ZES. Each patient also underwent preoperative localization studies. RESULTS: Thirty three of 35 patients (94%) had tumor detected and excised; duodenal gastrinomas were excised in 27 patients (77%). The average size of the duodenal tumors was 0.8 cm, significantly smaller (p < 0.005) than the pancreatic and lymph node tumors in this series. Standard palpation after a Kocher maneuver identified 19 of the 31 duodenal tumors (61%) in the 27 patients. IOUS revealed only eight duodenal tumors (26%) and no new lesions. IOE identified 20 duodenal gastrinomas (64%) and 6 new lesions. DX identified 31 duodenal tumors (100%) and 5 additional tumors. The morbidity rate was 17%. One patient had a duodenal fistula after operation (2.8%) and subsequently recovered. No patient died. CONCLUSIONS: These results demonstrate that the duodenum is the most common location for gastrinoma in patients with ZES (77%) and that DX to detect and remove duodenal gastrinomas should be routinely performed in all explorations for patients with ZES. PMID- 8342994 TI - Increased bile duct complications in liver transplantation across the ABO barrier. AB - OBJECTIVE: This study evaluated the outcome of liver grafts from ABO incompatible donors, focusing on biliary complications, and compared the results to an ABO compatible control group. Also, the expression of donor ABH antigens in the liver graft was analyzed. SUMMARY BACKGROUND DATA: The outcome of liver transplantation using an ABO incompatible graft is still debated. These blood group related (ABH) antigens are known to be expressed not only on the surface of the erythrocytes, but also on the epithelial cells of large bile ducts. Because the biliary epithelium of hepatic allografts may continue to express donor ABH antigens, it may be more susceptible to immunologic bile duct injury after transplantation across the ABO barrier. METHODS: Eighteen ABO incompatible grafts were compared with 18 ABO compatible grafts in patients who were matched according to medical urgency, primary liver disease (PLD), and recipient age. After transplantation, the grafts were analyzed with cholangiography, Doppler ultrasound, or arteriography and liver histology according to protocol. Immunoperoxidase staining for ABH antigens was performed on hepatic tissue. RESULTS: Biliary complications developed in 82% of the ABO incompatible donors, compared to 6% of the ABO matched controls. Hepatic artery thrombosis occurred in 24%. Cellular rejection was diagnosed in 65% versus only 28% in the control group. The 1-year actuarial graft survival rate was 44% versus 78% in the control group. ABH antigens of the donor were expressed on vascular endothelium and bile duct epithelial cells as long as 150 days after transplant. CONCLUSIONS: Using ABO incompatible allografts, a high incidence of biliary and hepatic artery complications and decreased graft survival in liver transplantation were found. An immunologic injury to the bile duct epithelium and/or to vascular endothelium is suspected. PMID- 8342996 TI - Endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations. AB - OBJECTIVE: This study was undertaken to prospectively evaluate the efficacy and safety of endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations. SUMMARY BACKGROUND DATA: Surgical therapy has been the traditional approach to large or unresolving biliary fistulas complicating liver transplantation. Although endoscopic management is rapidly becoming an acceptable alternative to surgery for the treatment of biliary fistulas complicating non-liver transplant hepatobiliary operations, it has received limited attention in the liver transplant setting. METHODS: During a 15-month period, 146 adults underwent liver transplantation with biliary reconstruction by end-to-end choledochocholedochostomy over a T tube. Inadvertent T-tube migration or intentional T-tube removal resulted in bile peritonitis in 18 patients. The patients were treated with a nasobiliary tube (n = 13), internal stent plus endoscopic sphincterotomy (n = 3), or internal stent alone (n = 2). Thirteen patients had a biliary fistula after other hepatobiliary operations and underwent endoscopic therapy during a similar period. All 13 had an endoscopic sphincterotomy with removal of obstructing stones when present (n = 6). Twelve patients also had stents placed. All patients were prospectively followed after hospital discharge and assessed for recurrent symptoms suggestive of biliary tract disease and procedure-related complications. RESULTS: Endoscopic retrograde cholangiopancreatography (ERCP) identified a biliary fistula at the T tube insertion site into the bile duct in all 18 liver transplant patients. Seventeen patients had resolution of their symptoms within 12 hours of therapy. The fistula sealed in 94.4%. In the other hepatobiliary operation group, ERCP demonstrated contrast extravasation from the biliary tree in 12 of 13. The biliary fistula closure rate was 92.3%. The endoscopic complication rate for the two groups was 3.2%. During a mean follow-up of 9 months, recurrent biliary tract complications occurred in 11.1% of the liver transplant group and 0% in the other hepatobiliary operation group (p > 0.05). The 30-day mortality rate was 0%. CONCLUSIONS: The results of this study support the application of endoscopic management of biliary fistulas complicating orthotopic liver transplantation and other hepatobiliary operations. This approach was relatively safe and obviated the need for surgical intervention. PMID- 8342995 TI - Macrophages produce nitric oxide at allograft sites. AB - OBJECTIVE: The current study was designed to determine which cytokines produced during an alloimmune response stimulate macrophage nitric oxide (.N = O) production at allograft sites. SUMMARY BACKGROUND DATA: Previous work has demonstrated that rat sponge matrix allograft infiltrating cells produce more .N = O on stimulation with alloantigen than syngeneic graft-infiltrating cells. Addition of NG-monomethyl-L-arginine (NMA), an inhibitor of .N = O synthesis, promotes allospecific cytolytic T-lymphocyte effector function. METHODS: Polyurethane sponges were implanted subcutaneously in recipient Lewis rats and injected with 10 x 10(6) ACl splenocytes. On various days after grafting, graft infiltrating cells were harvested for in vitro study. Adherent macrophages from the graft infiltrating cell population were obtained by a 2- to 3-hour incubation to plastic dishes with subsequent washing to remove nonadherent cells. RESULTS: Stimulation of unseparated graft-infiltrating cell populations with lipopolysaccharide or interferon-tau resulted in enhanced .N = O synthesis by allograft infiltrating cells compared with syngeneic graft-infiltrating cells, early after grafting. Macrophages recovered from an allograft site spontaneously produce more .N = O than macrophages recovered from syngeneic grafts (p < 0.001). Significantly enhanced levels of .N = O were produced by allograft macrophages compared with syngeneic graft macrophages on stimulation with lipopolysaccharide or interferon-tau (p < or = 0.025). CONCLUSIONS: Nitric oxide appears to be produced in response to the local cytokines secreted by an ongoing rejection reaction. Nitric oxide serves under these circumstances to modulate the alloimmune response. PMID- 8342997 TI - Bile secretion and liver regeneration in partially hepatectomized rats. AB - OBJECTIVE: The purpose of this research was to study the correlation between bile secretion and the liver regeneration in the partially hepatectomized rat. SUMMARY BACKGROUND DATA: Significant alteration in bile formation and secretion is expected in the liver after hepatectomy. There is scant literature, however, about the effects of liver regeneration in bile secretion. METHODS: The work was done in rats with 50% hepatectomy, 75% hepatectomy, and sham operation as the control. A chronic common bile duct fistula and a duodenal cannula were established for bile collection and the sample analysis on days 1, 3, 5, 7, and 9. RESULTS: With size reduced in the liver after 50% and 75% hepatectomy, the total bile volume decreased 45.9% and 51.5%, bile salt independent flow decreased 59.3% and 64.9%, bile salt secretion rate decreased 36.1% and 43.4%, bile salt basal synthesis rate decreased 52.3% and 56.4%, phospholipid secretion rate decreased 52.6% and 68.0%, and cholesterol secretion rate decreased 54.3% and 72.4% from control on day 1, respectively. All changes returned to the control level in 3 to 9 days with accompanying increasing liver size during regeneration. CONCLUSION: Alterations of total bile flow, bile salt independent flow, bile salt secretion rate, bile salt basal synthesis rate, and biliary lipid secretion after partial hepatectomy correlate with the liver regeneration rate in rats. Partial hepatectomy reduces the bile salt independent fraction calculated as per 100 g body weight rather than the dependent fraction. The study of bile salt and biliary lipid secretion is a useful method for monitoring synthetic function in liver regeneration in vivo. PMID- 8343000 TI - Are adults content or continent after repair for high anal atresia? A long-term follow-up study in patients 18 years of age and older. AB - OBJECTIVE: This study investigated the current state of fecal and urinary continence in an extensive group of adults after operative correction for high anorectal malformations and how they cope with their incontinence. SUMMARY BACKGROUND DATA: Normal fecal continence is hardly to be expected after correction for high anorectal malformation; despite this, it is commonly accepted that for most patients fecal continence improves with growing age and that most adult patients have no problems. Until now, however, few long-term follow-up studies in small groups of adults have been performed to assess continence after operative repair for high anorectal malformation. METHODS: Fifty-eight adult patients (median age, 26.0 years; range, 18.1 to 56.9 years) with an operatively corrected high anorectal malformation were evaluated by questionnaire with respect to their current state of fecal and urinary continence and mode of control of defecation. RESULTS: Seven patients have a permanent ileostoma or colostoma. Of the 51 patients with anal defecation, 61% control defecation by themselves, whereas 35% control defecation by using enemas or bowel irrigations, and 4% do not have any control at all. Besides medical therapy, 65% take dietary measures to influence defecation. According to existing scoring methods, 41% reached good and 49% fair control of defecation, whereas only 10% had poor control. Current control of defecation was reached from a median age of 15.0 years (range, 5 to 31 years). CONCLUSION: Conclusively, the authors can say that after correction for high anorectal malformation nobody reached normal fecal continence. Most patients with anal defecation reached good and fair control of defecation, however. Of all 58 patients, 84% are satisfied with their level of cleanliness. PMID- 8342999 TI - Survival with colorectal cancer in ulcerative colitis. A study of 102 cases. AB - OBJECTIVE: This study was undertaken to correlate postoperative survival of patients with ulcerative colitis-associated colorectal cancer with the stage, configuration, size, and mucin content of the tumor. SUMMARY BACKGROUND DATA: The factors influencing prognosis in colorectal cancer in the general population are well accepted, but less is known about their influence in cases of colorectal cancer associated with ulcerative colitis. METHODS: The authors reviewed the records of 102 patients with ulcerative colitis-associated colorectal cancer admitted to The Mount Sinai Hospital between 1959 and 1988. Tumors were classified on independent pathologic review according to histologic stage, configuration, size, and mucin content. Comparisons among survival curves were tested by the generalized Wilcoxon test. Cox regression models were used to examine the joint effects of selected clinicopathologic features on postoperative survival rates. RESULTS: Complete follow-up was obtained for 93 patients (92%). Overall 5-year actuarial survival was 52%. When factors were analyzed one at a time, survival was significantly poorer among patients with advanced cancer stage, larger tumor size, infiltrating and ulcerating configuration, and high mucin concentration. On multivariate analysis by the Cox regression model, however, only cancer stage emerged as a factor independently predicting survival. CONCLUSIONS: For colitis-associated colorectal cancers, as for noncolitic cancers, histologic stage is the most important variable determining postoperative survival. The distribution of stages in our series and the survival rates within each stage did not differ appreciably from the distributions and survival rates reported for noncolitic colorectal cancers. PMID- 8342998 TI - Developmental expression of the neurotensin gene in the rat liver. AB - OBJECTIVE: This study determined whether the neurotensin gene is expressed during early development of the liver. SUMMARY BACKGROUND DATA: Neurotensin (NT), a gut tridecapeptide localized mainly to the distal small bowel and brain of adults, is an important hormone regulating gut motility, secretion and mucosal growth. Expression of NT peptide and the gene is found in fibrolamellar hepatocarcinomas, a variant of hepatocellular carcinoma, but not in the normal adult liver. METHODS: Northern and in situ hybridization techniques were used to determine expression of the neurotensin gene (NT/N) in the normal developing liver. RESULTS: NT/N is expressed in the fetal and early postnatal rat liver, but expression is repressed in the liver of the adult. In situ hybridization confirms the authors' Northern data and demonstrates a random distribution of NT/N expression in the fetal and 3-day postnatal liver. CONCLUSIONS: The authors conclude from this study that NT/N is expressed during early development of the rat liver with subsequent repression in the adult. NT/N may be reexpressed with malignant transformation of the liver. PMID- 8343001 TI - Anal sphincter defects. Correlation between endoanal ultrasound and surgery. AB - OBJECTIVE: This study was performed to (1) correlate and sphincter defects, identified by endoanal ultrasound with operative findings, and (2) define the appearance of such sphincter defects as seen at operation. SUMMARY BACKGROUND DATA: Endoanal ultrasonography is a minimally invasive method of imaging the anal sphincter complex and enables identification of anal sphincter defects. Little is known about the accuracy and limitations of endoanal ultrasound in identifying such defects. Furthermore, there are no data about the appearances of these endosonic sphincter defects as seen at operation. METHODS: Forty-four patients (40 women; age range, 26 to 80 years; mean age, 56 years) with fecal incontinence, undergoing pelvic floor repair, were investigated by endoanal ultrasound before operation. Endosonic findings were correlated with the appearances of external anal sphincter, internal anal sphincter, and intersphincteric space, at operation. Diagnosis of the site and type of defect was made by macroscopic appearances. Uncertainty about the type of sphincter defect was resolved by obtaining muscle biopsies for histology. RESULTS: All external sphincter defects seen by endoanal ultrasound (n = 23) were confirmed at operation. Twenty-one of 22 internal sphincter defects identified by endosonography also were confirmed at operation. In ten patients with a neuropathic anal sphincter complex, the morphology was normal on endosonography, and this was confirmed at operation. (Sensitivity and specificity of 100% for external anal sphincter; 100% and 95.5%, respectively, for internal and sphincter) CONCLUSIONS: These data show that endoanal ultrasound is an accurate method of identifying anal sphincter defects. PMID- 8343003 TI - Surgical strategy of extended lymphadenectomy for esophageal carcinoma. PMID- 8343002 TI - A prospective, randomized evaluation of the effect of silver impregnated subcutaneous cuffs for preventing tunneled chronic venous access catheter infections in cancer patients. AB - OBJECTIVE: This study was performed to evaluate the effect of a silver impregnated cuff on the incidence of catheter-related bacteremia/fungemia or tunnel tract infection in cancer patients with chronic dual-lumen tunneled venous access catheters. SUMMARY BACKGROUND DATA: Infection is a frequent and potentially life-threatening complication of tunneled chronic cuffed silastic central venous access catheters in cancer patients. Recent experience with antimicrobial silver-impregnated cuffs placed on nontunneled percutaneously inserted central venous catheters suggests that such a cuff may render the catheter less prone to infection. METHODS: The authors prospectively randomized 200 cancer patients to receive either a dual-lumen 10 French tunneled cuffed silastic central venous access catheter or the same catheter with a second more proximal subcutaneous silver-impregnated cuff. All patients then were followed prospectively for infectious morbidity until the device was removed or the patient died. RESULTS: The hazard rate for infection/day (95% confidence limits) was 0.0022 (0.0015 to 0.0030) for standard catheters compared with 0.0027 (0.0019 to 0.0037) for catheters with silver-impregnated cuffs (p = not significant). Regression analysis of infection-free interval of both catheter types shows no difference over the lifetime of catheter as well as the over the first 48 days after insertion. CONCLUSIONS: The study indicated no effect of a silver impregnated cuff in decreasing the incidence of catheter-related bacteremias/fungemias, tunnel infections, or the spectrum of causative microorganisms involved in cancer patients with tunneled chronic venous access catheters. PMID- 8343004 TI - Laparoscopic bile duct injuries. PMID- 8343005 TI - Routine operative cholangiography in patients undergoing laparoscopic cholecystectomy. PMID- 8343006 TI - Multiple (systems) organ failure [M(S)OF] is an unbridled inflammatory response. PMID- 8343007 TI - Multiple (systems) organ failure [M(S)OF] is an unbridled inflammatory response. PMID- 8343008 TI - Computerized morphometric analysis of the chick embryo esophagus. AB - By means of a computerized morphometric system and a semiautomatic digital system (videoplan II), the quantitative aspects of the organogenesis of the chick embryo esophagus were investigated from the 6th to the 15th day of incubation. The area of the total section, of the lumen, of the wall and its components (subserous stratum, muscle layer, lamina propria and epithelium) and the thickness of the epithelium and the muscle layer were measured. The mean area +/- S.E.M. of the values obtained was calculated. The percentage of shrinkage, due to the histological procedures, was calculated for each day. The mean values for each day of incubation were modified on the basis of the shrinkage percentage. Exponential curves and r coefficient were determined to evaluate the growing pattern of the mean area of the esophageal wall components as a function of age. The main results are the following: 1) From the 6th to the 10th day of incubation the areas of all the wall components show an increase. 2) From the 11th day onwards, the wall components undergo a different growth pattern; in fact, the area of the subserous stratum decreases from the 11th to the 13th day, the muscle layer and the lamina propria show a decrease on the 12th day, while the growing pattern of the epithelium area appears irregular from the 12th day onwards. 3) The lamina propria results to be the component of the wall that shows the highest growth rate. Moreover, the esophageal anlage shows different developmental behaviour compared with that of the other intestinal tracts previously examined (ileum, duodenum, colon, caeca) in the same chick embryo. PMID- 8343009 TI - Further observations on the morphology and sensitive innervation of the retractor penis muscle in several species of ungulates. AB - The retractor penis muscle originates from the vertebrae in pigs, horses, cattle and goats; it arises from the rectum in sheep. In all the species considered, sensitive innervation was found. This was represented by encapsulated receptors. Nervous vegetative supply, made up of isolated or assembled ganglion cells, was also present. Among the numerous sensory nerve endings found in pigs, goats and sheep were Pacinian, Pacinian-like, Golgi-Mazzoni corpuscles and Krause's end bulbs (genital corpuscles). Few Pacinian and Pacinian-like corpuscles were found in cattle and horses. A hypothesis on the probable functional role of the observed receptorial apparatus was formulated. PMID- 8343010 TI - The anatomy and clinical significance of the collateral circulation between the internal and external carotid arteries through the ophthalmic artery. AB - Complete occlusion of the internal carotid artery is not necessarily associated with total disruption of cerebral blood flow distal to the site of the arterial obstruction. In fact, the flow of blood may be sufficient to maintain cerebral perfusion. This is accomplished by the shunting of blood from the external to the internal carotid artery by means of collateral circuits. While several major branch arteries of the external carotid artery may be recruited in this process, the ophthalmic artery is often the final common pathway before the anastomosis with the internal carotid artery. With the aim of elucidating these collateral circles, digital subtraction angiography was used to examine 100 patients with total occlusion of the internal carotid artery. These data were compared with those obtained using Doppler ultrasound, duplex scanning, and transcranial Doppler. Forty patients were excluded because there was no demonstrable collateral circulation, because the collateral circulation used the communicating arteries, or because the ophthalmic artery arose from the middle meningeal artery. Dynamic data were obtained by compressing the branches of the two external and common carotid arteries, and the blood vessels were identified by comparison with previous anatomic studies. We have constructed a precise map of the intra- and extracranial circles that connect the internal and external carotid arteries through the pathways that include the ophthalmic artery. This map demonstrates why apparently identical vascular occlusions may have divergent symptomatologies and clinical outcomes, which may range from the complete absence of symptoms to cerebral infarction. PMID- 8343011 TI - Interaction between keratinocytes and fibroblasts cultured in vitro: morphology, morphometry and growth. AB - In order to elucidate the interactions between fibroblasts and keratinocytes co cultured in vitro, the morphology and growth of rat keratinocytes cultured with and without a feeder layer were compared. Morphological analysis was coupled with a simple morphometric method of image analysis performed with a computer aided system to demonstrate statistically significant differences between keratinocyte cultures obtained with and without a feeder layer. Epidermal cells cultured without fibroblasts but with a conditioning medium showed a slower growth rate and significant a greater cellular dimensions in comparison with cells grown in the presence of a feeder layer. These results suggest that the conditioning medium induces a morphological change of keratinocytes. The electrophoretic patterns of proteins extracted from cells cultured with and without a feeder layer were identical, whereas densitometric analysis revealed that the quantitative expression of proteins was clearly different. These data confirm that of keratinocyte growth is dependent on fibroblasts or fibroblast products. PMID- 8343012 TI - The sulci of the cuneus of the human cerebrum. AB - The limiting and internal sulci of the cuneus of the occipital lobe of 80 cerebri of Brazilians of either sex (24 females and 56 males) were studied and findings were correlated with each hemisphere and the sex of the individuals. The distribution of the material was 39 Caucasians (11 females and 18 males) and 41 non-Caucasians (13 females and 28 males). The limiting sulci, namely parieto occipital and calcarine, were found in all cases. The internal sulci were classified in horizontal, oblique, vertical and cuneolingual. The cuneus of the right cerebral hemisphere had more sulci than that of the left. The cuneus had also more sulci in males than in females. PMID- 8343013 TI - [Oral rice-based rehydration solution (SRO), alternative of SRO of WHO in acute diarrhea in malnourished patients]. AB - BACKGROUND: Although malnutrition is frequently associated with diarrhea, most oral rehydration solutions have been tested in well-nourished children. The study tests efficacy of rice, a traditional treatment for diarrhea in Madagascar. PATIENTS AND METHODS: 150 severely malnourished children, aged 6 months to 3 years, took part in this randomized trial. All the children were given oral rehydration solution, (100 ml/kg) in the first 6 hours. The first group (68 children) was given a solution containing glucose, (20 g/l). The second group (82 children) was given a solution containing rice powder (50 g/l). Treatment was then continued according to WHO recommendations, including feeding after rehydration (mixture of milk, oil and sugar). RESULTS: The age, weight, height, duration of diarrhea before admission, degree of dehydration and pathogens in stools of the two groups were comparable on admission. Only 2 patients were withdrawn from the trial. The percentage of death was the same in both groups: 16% of those given glucose and 15% of those given rice-based rehydration solution. The weight gains were similar in both groups; the duration of diarrhea was 89 +/- 6 hours in the glucose-fed groups and 68 +/- 4 hours for those given the rice-based rehydration solution (p < 0.02). CONCLUSIONS: Both glucose and rice-based rehydration solutions are equally effective for rehydrating severely malnourished children with acute diarrhea. The rice-based rehydration solution also reduces the duration of diarrhea. PMID- 8343014 TI - [Congenital obstruction of lacrimal ducts in 578 children]. AB - BACKGROUND: Congenital obstruction of the nasa lacrimal ducts is a frequent problem in infancy. Its management is still controversial. REPORT: 578 children aged 6 weeks to 3 years were treated in our department between 1980 and 1987. Congenital obstruction of the nasa lacrimal ducts was bilateral in 172 of them, so that a total of 750 ducts were obstructed. All the infants were treated with antibiotics until they are 2 months old. Permeability was obtained in 97% of the 750 obstructed ducts: this was spontaneous in 38.7%, after a single wash in 3%, and by probing under general anesthesia in 55.3%. The percentage of cases requiring surgery increased with age at time of diagnosis. CONCLUSIONS: The best results are obtained in infants 2 to 4 months old. PMID- 8343015 TI - [Value of dexamethasone in purulent meningitis in children. Apropos of a comparative study of 85 children]. AB - BACKGROUND: The beneficial effect of dexamethasone plus antibiotic therapy in bacterial meningitis is still controversial. PATIENTS AND METHODS: Eighty-five children, aged 1 month to 14 years, were admitted between 1987 and 1990 for bacterial meningitis. They received the same antibiotic therapy for 10 days (7 days in meningococcal meningitis). The 44 children admitted since March 1989 were also given dexamethasone (0.15 mg/kg/6 hours for 4 days); the first injection was given before antibiotic therapy. Clinical (fever, neurological findings, audition) and laboratory data [CSF proteins, glucose, lactate, cell and bacterial counts; blood C-reactive protein (CRP), hemoglobin, leukocytes and platelets] were analyzed statistically. RESULTS: The group treated with antibiotics plus dexamethasone showed decreases significantly greater in CSF protein and lactate levels after 48 hours than the children given antibiotics alone and an early (6 hours after the start of treatment) increase in CSF glucose. The blood CRP level of the dexamethasone plus antibiotics group decreased significantly within 48 hours. The numbers of neurological sequelae and deaths in this group were clearly lower than for the antibiotic group, but the risk of deafness did not appear to be altered. CONCLUSIONS: These results confirm the beneficial effect of dexamethasone reported earlier. The relatively frequent transient recurrences of fever and increased CRP when dexamethasone was interrupted suggest that the dose and/or duration of dexamethasone treatment should be modified. PMID- 8343016 TI - [Huntington chorea in children]. AB - BACKGROUND: The onset of Huntington's disease, a dominantly inherited degeneration of the basal ganglia, usually occurs in middle age; cases of childhood onset are rare. CASE REPORTS: Case 1. A boy from a family including several cases of Huntington's disease gradually developed behavior disorders from the age of 5 years. He had learning and language disorders at 7 years of age and at 11 years he suffered from generalized seizures and progressive rigidity. The disease led to dementia at 17 years and the patient died a few months later. CT scan showed diffuse cortical atrophy. Case 2. A girl aged 5 years, was first examined for gait disorders. At that time she had dystonia and spasticity. Rigidity gradually developed, and 2 months later several cases of Huntington's disease were identified in her father's family. Case 3. A boy developed gait disorders from the age of 5 years. He gradually developed dystonia, rigidity, learning disorders, and finally mental retardation. The CT scan showed cortical atrophy and atrophy of the caudate nucleus. His father and others members of the paternal family had Huntington's disease that appeared in the adulthood. CONCLUSION: The clinical manifestations of Huntington's disease in childhood are different from those seen in adults. Progressive alteration of mental development and dementia can occur. Diagnosis may be difficult except when a parent has the fully developed disease. PMID- 8343017 TI - [Unusual intrathoracic tumor in children: lipoma]. AB - BACKGROUND: Intrathoracic lipomas are rare, often asymptomatic and, in this case, discovered by chance on X-ray. CASE REPORT: A 3 year-old girl was admitted because chest X-rays prescribed for a persistent cough showed a mass in the right axillary area. The CT scan showed a mass with density of -80 Hounsfield units, characteristic of adipose tissue. There was a slight rib change in contact with the mass, but radionuclide bone scan showed no area of increased uptake. A chest X-ray performed 3 years earlier had shown such a mass, but it was not recognized at that time. Surgery demonstrated that the mass was extrapleural in location and adhering to the rib which was partly excised. Histologic examination showed the presence of mature adipocytes, but no malignant cells. CONCLUSION: The fatty component of an intrathoracic tumor is easily recognized with CT scan. Erosion of bone in contact with it has been reported. PMID- 8343019 TI - [Neonatal septicemia due to Pneumococcus resistant to beta-lactam antibiotics]. AB - BACKGROUND: Neonatal sepsis due to Streptococcus pneumoniae is relatively rare. The increasing risk that this bacterium is resistant to betalactam antibiotics worsens its prognosis. CASE REPORT: A newborn was delivered by cesarean section because of an abnormal fetal heart rate pattern. Despite intubation, respiratory support and correction of acidosis, the baby remained cyanotic and displayed signs of shock. Neutropenia, increased percentage of immature neutrophils, high C reactive protein levels and an X-ray pattern of pneumonia also indicated an infection. The child was given symptomatic therapy, and amoxicillin, cefotaxime and amikacin. Pneumococci type 9 were isolated from peripheral secretions and from the blood. Deterioration of the respiratory condition required higher doses of amoxicillin and cefotaxime on day 2 pending the results of antibiotic sensitivity testing. This test showed that the strains were resistant to beta lactam antibiotics. On day 3, the treatment was replaced by a combination of vancomycin, rifampicin, amikacin and cefotaxime. This treatment was pursued for 2 weeks, except for rifampicin which was stopped after 2 days. The follow-up was uneventful. A search for pneumococci in the mother was negative. CONCLUSIONS: Streptococcus pneumoniae should always be considered as a cause of neonatal sepsis. Poor therapeutic control indicates resistance to beta-lactam antibiotics. This patient may be the first reported case of maternal-fetal infection with this resistant strain. PMID- 8343018 TI - [Dwarfism, arterial hypertension and hyperkalemic acidosis corrected with thiazides. A case of type II pseudohypoaldosteronism]. AB - BACKGROUND: Type II pseudohypoaldosteronism is a rare tubulopathy defined by abnormal renal potassium excretion. CASE REPORT: A 12 1/2 year-old girl, was admitted for dwarfism. Her parents were not consanguineous and her 5 living sibs were normal. At admission, she had moderate hypertension: systolic 130-150 mmHg; diastolic 80-100 mmHg and no pubertal development. LABORATORY DATA: pH (arterial): 7.34; bicarbonates: 18-20 mEq/l; chloride: 112-120 mEq/l; potassium: 5.6-7 mEq/l; aldosterone: 200-700 pg/ml (N < 60); plasma renin activity: 0.4 ng/ml/hr (N 2.2 +/- 0.2). The bone maturation was 8 1/2 years. All the other renal function tests were normal. The titratable acidity was 22 mEq/day (N 20-40) and the ammonia excretion 15.2 mEq/l (N 44-61). The fractional excretion of potassium was 6.5% (N 11.8 +/- 1.9). This girl was given polystyrene sulfonate resin followed by hydrochlorothiazide (1 to 3 mg/kg/day). There was a subsequent improvement in all data, a growth spurt and pubertal development. CONCLUSION: This is the fifth case of type II pseudohypoaldosteronism reported in childhood and the first one with hypertension. The beneficial effect of hydrochlorothiazide is underlined. PMID- 8343020 TI - [Stark-Kaeser type scapulo-peroneal amyotrophy of neurogenic origin. Study of a familial case]. AB - BACKGROUND: There are several types of the rare syndrome, scapuloperoneal atrophy; the report deals with a familial case of the Stark-Kaeser type. CASE REPORT: A 16 year-old Tunisian boy was admitted for "steppage" gait. His mother had distal myoatrophy of four limbs and pes cavus. His sister, aged 8 years, also had pes cavus. She had no tendon reflexes and electromyography showed evidence of muscular denervation with normal nerve conduction velocity. The "steppage" gait in our patient began when he was 6 years old. When he was examined at 16 years, there were bilateral atrophy of the sternocleidomastoid muscle, and atrophy of the scapular girdle and the peroneal muscles with loss of tendon reflexes; there was no sensory involvement. Nerve conduction velocity was normal and electromyography showed fibrillation and pseudomyotonia potentials. Creatine kinase activities were moderately increased. Muscle biopsy showed significant neurogenic type changes. CONCLUSION: This patient has a Stark-Kaeser type spinal amyotrophy, a well-individualized entity due to progressive degeneration of the anterior horn cells. PMID- 8343021 TI - [C2 deficiency discovered in pneumococcal meningitis]. AB - BACKGROUND: Congenital deficiencies of complement system proteins are rare. Patients with C2 deficiency have a high incidence of vascularitis syndromes. Most patients with this deficiency have no problems with increased susceptibility to infection, most commonly due to pneumococci, presumably because of the protective function of the alternative pathway. CASE REPORT: A 22 month-old girl was admitted because of acute meningitis and otitis. She had had 2 episodes of otitis media at the age of 1 year. Analysis of the CSF showed that this meningitis was due to pneumococcal infection. Recovery was complete after 15 days of antibiotic therapy. Total hemolytic complement activity (CH50) was low during the infection; one month later, the CH50 value was about zero as was C2, while C3 and C4 were normal. The patient was given polyvalent pneumococcal and anti-Haemophilus vaccines plus prophylactic penicillin G. Laboratory tests for systemic lupus erythematosus were negative. CONCLUSION: A defect of complement function should be suspected in any patient with severe of recurring pyogenic infections. Complement disorders can be detected one month later by means of the relatively simple hemolytic complement assay. PMID- 8343022 TI - [Iconographic rubric. Metastatic pulmonary calcifications in a child]. PMID- 8343023 TI - [Behcet disease in children]. PMID- 8343024 TI - [Development of body image in adolescents. Psychosocial determinants and behavioral effects]. PMID- 8343025 TI - [Recent progresses in neonatology]. PMID- 8343026 TI - [Flow rate through Vialon peripheral catheters, after used in children]. PMID- 8343027 TI - [Catheter breakage at the point of insertion into a pediatric implantable system]. PMID- 8343028 TI - [A case of peritoneal tuberculosis]. PMID- 8343029 TI - [Digestive form of Langerhans cell histiocytosis]. PMID- 8343030 TI - [Peanut allergy, iatrogenic disease?]. PMID- 8343031 TI - [Massive feto-maternal hemorrhage and prevention of Rhesus feto-maternal incompatibility]. PMID- 8343032 TI - [Plea for a specialty of medical genetics]. PMID- 8343033 TI - [Manner of birth and otitis media]. AB - BACKGROUND: There are many risk factors associated with the occurrence of otitis media; cesarean section could be one of them. REPORT: Two hundred and eighty four children were treated during the first three years of life by the same pediatric service. 47% of these children were treated for otitis media and 53% were not. 41% were delivered by cesarean section, and 59% were vaginal births. The incidence of otitis media in the cesarean section group was 0.504, versus 0.449 in the vaginal birth group. RESULTS: These data indicate that the fraction of risk of having otitis media that is attributable to cesarean section is 11%; the relative risk is 1.12. CONCLUSION: The observed effect is not large enough to confirm that cesarean section is a risk factor, but suggests that a carefully controlled prospective study should be conducted. PMID- 8343034 TI - Effects of clozapine and fluphenazine treatment on responses to m chlorophenylpiperazine infusions in schizophrenia. AB - OBJECTIVE: To explore serotonin function in patients with schizophrenia during typical and atypical neuroleptic treatment. We hypothesized that clinically relevant doses of the atypical neuroleptic clozapine would attenuate responses to the serotonin agonist m-chlorophenylpiperazine (m-CPP). DESIGN AND INTERVENTIONS: m-CPP or placebo was administered intravenously over 90 seconds to patients who had been receiving no medications for at least 3 weeks. m-CPP was also administered during treatment with the typical neuroleptic fluphenazine and the atypical neuroleptic clozapine. PATIENTS: Fifteen inpatients (two women and 13 men) who met DSM-III-R criteria for chronic schizophrenia (n = 13) or schizoaffective disorder (n = 2) participated in the study. Mean age (+/- SD) was 33.8 +/- 8.0 years. MAIN OUTCOME MEASURES: Measures of m-CPP effects included plasma cortisol and prolactin, body temperature, and the Brief Psychiatric Rating Scale (BPRS). The final BPRS total score at approximately 12 weeks of treatment was used to assess response to clozapine. RESULTS: m-CPP infusion significantly increased plasma cortisol and prolactin levels in drug-free patients. There was a range of behavioral responses while drug-free, but no statistically significant effects on BPRS total or BPRS factor scores. Clozapine treatment significantly blocked neuroendocrine responses to m-CPP, whereas fluphenazine had no effect. Clozapine also appeared to attenuate behavioral responses. CONCLUSIONS: These results demonstrate that clozapine treatment has potent serotonin antagonist effects in patients with schizophrenia. This may be related to clozapine's therapeutic effects since patients with greater cortisol response to m-CPP while drug-free had a better subsequent response to clozapine. PMID- 8343035 TI - The Roscommon Family Study. II. The risk of nonschizophrenic nonaffective psychoses in relatives. AB - OBJECTIVE: We sought to clarify the familial relationship between the nonschizophrenic, nonaffective psychoses (schizoaffective disorder [SAD], schizophreniform disorder, delusional disorder, and atypical psychosis) and schizophrenia and affective illness (AI). DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. RESULTS: Compared with relatives of unscreened controls, the risk of nonschizophrenic, nonaffective psychoses was significantly elevated in relatives of probands with schizophrenia, SAD, schizotypal personality disorder, and psychotic AI. No significant elevation in risk to these disorders was seen in relatives of probands with nonpsychotic AI. The risk for SAD alone was significantly increased in relatives of probands with psychotic or bipolar AI. CONCLUSIONS: The nonschizophrenic, nonaffective psychoses have a significant familial relationship with both schizophrenia and schizotypical personality disorder. Schizoaffective disorder, as defined by DSM III-R, shares familial etiologic factors with at least some forms of AI. PMID- 8343036 TI - Research activities of full-time faculty in academic departments of psychiatry. AB - Using data collected by a 1989 American Psychiatric Association survey of full time, salaried faculty in departments of psychiatry at US medical schools, we examined the number of faculty engaged in research, their levels of involvement in research, distribution, sources of funding, fields and topics studied, and training. Using a three-level measure of research involvement, we categorized 39.1% of the respondents as "researchers," 36% as "limited commitment researchers," and 25.1% as not involved in research. In a pattern similar to that observed for research funding in other studies, half of the researchers were concentrated in the top 15 of the 116 responding departments. Level of research involvement varied by degree type (joint-program MD/PhDs were most involved), sources of funding, fields, and topics. Among faculty with MDs, having had research experiences in medical school or postdoctoral research training was associated with a higher level of research involvement. The findings underscore the need to expand and improve postdoctoral research training--especially for MDs -and programs to recruit college and medical students into psychiatric research. PMID- 8343037 TI - In memoriam Daniel X. Freedman, MD August 17, 1921, to June 3, 1993. PMID- 8343038 TI - Alfred Adler's description of the case of Vaslav Nijinsky in light of current diagnostic standards. PMID- 8343039 TI - Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue and monocytoid B cell lymphoma. Related entities that are distinct from other low-grade B-cell lymphomas. PMID- 8343040 TI - Proficiency testing in clinical cytogenetics. A 6-year experience with photographs, fixed cells, and fresh blood. AB - The College of American Pathologists and the American Society of Human Genetics offer a proficiency testing program in clinical cytogenetics. Two hundred twenty five laboratories now provide data for this survey, which was begun in 1986. Challenges have consisted of photographed metaphases, fixed lymphoblastoid cell suspensions, fresh peripheral blood, and disarranged karyotypes. The "correct" response was based on 80% or greater consensus among either the referees or the participants. Referee laboratories performed better than participants. More laboratories were able to report accurate recognition of abnormalities by using a coded list than could write the interpretation in standardized nomenclature. Deletions, unbalanced translocations, and inversions were more difficult challenges than balanced translocations or trisomies. Prenatal and lymphocyte challenges were more likely to result in consensus than were bone marrow challenges. Participants performed best on whole-blood challenges. Fixed cell suspensions were less satisfactory. Excellent quality case material is essential for a successful challenge. A grading system has been devised to separate artifacts of the survey process from proficiency variables. PMID- 8343041 TI - Detecting semen antisperm antibodies in the clinical laboratory. AB - Although antisperm antibodies are associated with infertility, many hospital laboratories do not test for these antibodies. This study included 520 males who were referred for infertility evaluation. Semen samples from all patients were tested for antisperm antibodies by using the mixed antiglobulin reaction and immunobead binding tests. These results were correlated with the findings of semen analyses, postcoital tests, and sperm penetration assays. Eighty-eight men (16.9%) tested positive for IgG, IgA, or IgM antisperm antibodies. More samples tested positive for IgG antibodies by the mixed antiglobulin reaction than by the immunobead test (n = 71 vs n = 42); 57 samples tested IgA positive. Both methods showed good reproducibility (97.6%). Antibody-positive males had a higher incidence of abnormal semen analyses (92% vs 74%) and other immune-related fertility test results (94.2% vs 38.4%). The presence of antisperm antibodies correlates with other abnormal semen parameters. Testing for these antibodies should be included in an infertility evaluation and could be readily implemented in a clinical laboratory. PMID- 8343043 TI - Adenoid cyst-like carcinoma of the prostate gland. AB - Adenoid cyst-like carcinoma of the prostate is a rare but distinctive variant of prostatic adenocarcinoma. Adenoid cystic carcinoma is most commonly encountered in the salivary glands, and the cell of origin is thought to be the myoepithelial cell. Electron microscopic studies of the human prostate have not revealed myoepithelial differentiation. Myoepithelial cells of the human prostate are thought to arise in seromucinous ectopic glands. A case of adenoid cyst-like carcinoma of the prostate gland is documented, and the histological, immunohistochemical, and electron microscopic features of this tumor are discussed. These features are compared with five cases of classic salivary gland adenoid cystic carcinoma. To define the myoepithelial cell population of the prostate gland, 12 normal prostate glands were studied. Prostatic adenoid cyst like carcinoma differs from adenoid cystic carcinoma of salivary gland origin, and it is therefore postulated that the behavior of these tumors may likewise differ. PMID- 8343042 TI - Computerized static DNA ploidy analysis of prostatic intraepithelial neoplasia. AB - The microscopic features of prostatic intraepithelial neoplasia (PIN) are said to identify a precursor of prostatic adenocarcinoma (PC). We investigated this sequence of neoplastic progression by studying the relationship of PIN and PC by static ploidy analysis so that PIN and PC nuclei could be distinguished morphologically from each other and separately analyzed. From 51 archival cases of PC with coexistent high-grade PIN (PIN grades II and III) 50 control nuclei, 100 PIN nuclei, and 100 carcinoma nuclei per case were identified and digitized in corresponding Feulgen-stained slides. Control and PIN ploidy histograms fit a log-normal distribution, whereas malignant nuclei fit a rectangular distribution. When the histogram patterns were classified, the incidence of aneuploidy was 25% in PIN and 41% in PC. By case, the concordance of ploidy between PIN and PC was heterogeneous, yet the DNA ploidy of PIN and the corresponding PC was significantly associated. In four cases, PIN was DNA aneuploid while the associated PC was DNA diploid. These results support the hypothesis that high grade PIN is a neoplastic precursor of prostatic adenocarcinoma and suggest that further karyotypic instability may result in invasive adenocarcinoma with different DNA content detectable by image analysis. PMID- 8343044 TI - Succinylated wheat germ agglutinin lectin binding in intrahepatic vessels. A new histochemical tool. AB - Succinylated wheat germ agglutinin, specified by the amino sugar beta(4)-N acetylglucosamine, bound frequently to the endothelial cells of the hepatic arterial branches and small vessels of the peribiliary capillary plexus, while it did not bind to the endothelial cells of venous vessels such as portal vein branches and hepatic venous radicles, nor to lymphatic vessels. Sinusoidal endothelial cells were also negative for succinylated wheat germ agglutinin. Proliferating small vessels in the enlarged portal tracts and fibrous septa in patients with extrahepatic biliary obstruction or chronic active hepatitis with or without cirrhosis tended to be positive for succinylated wheat germ agglutinin. Such findings have not been previously reported, to the best of our knowledge. Thus, succinylated wheat germ agglutinin may be a new and useful histochemical tool in routinely processed tissue sections to discriminate intrahepatic vessels into several categories, particularly into two categories (arterial and other vessels), in normal as well as diseased livers. PMID- 8343046 TI - Gastric syphilis. Primary diagnosis by gastric biopsy: report of four cases. AB - Gastric involvement in secondary or tertiary syphilis is rarely recognized clinically, and its diagnosis by examination of endoscopic biopsy specimens has been reported infrequently. We report four cases of gastric syphilis with the primary diagnosis made by gastric biopsy. The patients, all male, ranged in age from 38 to 78 years and presented with gastric complaints, the most common being upper gastrointestinal tract bleeding (three of four). Gastroscopy showed either erosive gastritis or gastric ulcers with heaped, nodular edges. The clinical diagnoses ranged from benign ulcer disease to infiltrating carcinoma and lymphoma. Gastric biopsy specimens in all cases showed a severe gastritis with dense plasmacytic infiltration, associated with varying numbers of polymorphonuclear leukocytes and lymphocytes, variable degrees of glandular destruction and reactive atypia, and a vasculitis without proliferative changes. Modified Steiner silver impregnation stain revealed numerous spirochetes in all four cases and associated Helicobacter pylori infection in one case. Serologic studies for syphilis were positive in all four cases (rapid plasma reagin test, fluorescent treponemal antibody absorption test). None of the patients were seroreactive for antibodies to human immunodeficiency virus. These recent cases of gastric syphilis emphasize the importance of remaining alert to the protean clinical manifestations of syphilis and aware of the histopathologic patterns of this disease. PMID- 8343045 TI - Diffuse lymphoplasmacytic infiltration of the small intestine with damage to nerve plexus. A cause of intestinal pseudo-obstruction. AB - We describe the clinicopathologic characteristics of three patients with chronic intestinal pseudo-obstruction and malabsorption. The patients were young women (average age, 25 years) who presented with abdominal pain, nausea, vomiting, diarrhea, and weight loss that led to extreme inanition and death in two patients despite multiple treatment schemes. The evolution of the process averaged 8 years. No case manifested evidence of malignant lymphoproliferative progression. Histologically, a diffuse lymphoplasmacytic infiltrate that affected all the layers of the intestinal wall was observed in full-thickness biopsy specimens. The proliferating lymphocytes were small and mixed with mature plasma cells that proved to be polyclonal on immunohistochemical analysis. An outstanding finding in all three cases was extensive damage to submucosal and myenteric nerve plexus associated with a lymphoid infiltrate. Quantification of the myenteric plexus by using immunohistochemical and morphometric techniques also revealed a marked reduction in their number. We concluded that diffuse lymphoplasmacytic infiltration of the small intestine associated with damage to the intestinal nerve plexus constitutes a specific disorder that is different from other diseases that produce intestinal pseudo-obstruction. PMID- 8343047 TI - The prognostic value of human chorionic gonadotropin expression in colorectal adenocarcinomas. An immunohistochemical study of 102 stage B2 and C2 nonmucinous adenocarcinomas. AB - Several recent studies have detected human chorionic gonadotropin (hCG) expression in colorectal adenocarcinomas and have concluded that its expression is an adverse prognostic indicator. The patient population and length of follow up has varied. Therefore, we reviewed a defined group of cases with long-term (> 5 years) follow-up. We studied 102 stage B2 and C2 nonmucinous adenocarcinomas immunohistochemically for the production of hCG. Expression of hCG was detected in paraffin sections, including tumor and adjacent mucosa, using immunolabeling with a polyclonal rabbit antibody and the avidin-biotin-peroxidase complex technique. Cytoplasmic positive staining was evaluated semiquantitatively in every low-power microscopic field containing tumor. Expression of hCG was noted in at least one field in 42% (43/102) of the carcinomas. There was no expression in adjacent mucosa. Although the staining was usually focal (< 5% of tumor cells), some cases did stain diffusely. There was no significant correlation of hCG expression with survival, stage, differentiation, age, race, sex, or site of tumor. We therefore conclude that hCG expression is not a significant prognostic indicator in stage B2 and C2 colorectal carcinomas. PMID- 8343048 TI - Pulmonary tumor embolism to arterial vessels and carcinomatous lymphangitis. A comparative clinicopathological study. AB - A prospective study of 222 consecutive autopsies of cancer cases was undertaken to investigate whether carcinomatous lymphangitis and pure arterial tumor embolism of the lungs are different clinicopathological entities. The lungs were removed as a block and 15 sections (three from each lobe) were analyzed. A protocol containing clinical (ie, dyspnea, cyanosis, right ventricular failure, engorgement of jugular veins, and peripheral edema as main cause of death) and morphological (ie, right ventricle thickness and dilatation, vascular sclerosis, pulmonary infarct) data were carefully recorded in each case. Arterial tumor embolism was detected in 19 cases (8.5%) and carcinomatous lymphangitis in 44 cases (19.8%). We found no differences in relation to signs and symptoms of arterial tumor embolism and carcinomatous lymphangitis, but respiratory distress as the main cause of death was significantly more frequent in the cases with arterial involvement by tumor emboli. Morphologically, however, right ventricular hypertrophy-dilatation, histological signs of pulmonary hypertension, and hemorrhagic infarcts were more prevalent in the cases with arterial tumor embolism. This study permits us to conclude that although arterial tumor embolism and carcinomatous lymphangitis are clinically similar diseases, they are morphologically different entities. Our results suggest that the most probable pathogenesis of pulmonary endarteritis and subsequent pulmonary hypertension is the injury to the vascular endothelium caused by the arrest of tumor emboli. PMID- 8343049 TI - Development of chronic renal failure in patients with multiple myeloma. AB - Glomerulotubular disconnections at the immediate postglomerular segment of the proximal tubules, accounting for an impaired renal function, were demonstrated recently in several chronic nonglomerular renal disorders. To analyze the glomerulotubular junctions in Bence Jones cast nephropathy, paraffin blocks from the kidneys of nine deceased patients with myeloma and chronic renal failure on whom autopsies were performed were studied in serial sections. Kidneys from seven deceased patients without renal disease on whom autopsies also were done served as controls. For stereological estimations, the percentages of patent and sclerosed glomerular profiles, the relative volume fractions, and the absolute volumes of the interstitium, tubules, and glomeruli were determined. In Bence Jones cast nephropathy, 96% of the glomerular profiles were patent, and the reconstruction of randomly chosen glomerulotubular junctions revealed that 84% of the patent glomeruli had normal tubular connections. There was an increased relative interstitial volume (fibrous tissue) and a decreased relative tubular volume. The absolute values indicated severe interstitial fibrosis, but not tubular atrophy. The results show that in contrast with other chronic nonglomerular nephropathies, chronic renal failure in Bence Jones cast nephropathy does not result from nephron disconnection at the immediate postglomerular segment of the proximal tubules. The main factor responsible for the decrease in renal function appears to be the progressive severe fibrosis of the interstitium. PMID- 8343050 TI - Osteolytic phaeohyphomycosis caused by Phialemonium obovatum. AB - Phialemonium obovatum was found to be the cause of nosocomial osteomyelitis in a 41-year-old man after sustaining a nonpenetrating injury to his lumbar and cervical region. Histologic examination of fragments of disk and bone from L3-4 hemilaminectomy showed multiple fragments of fibrocartilage with focal necrosis, chronic inflammation, and granulation tissue formation. Sections stained with Gomori's methenamine silver procedure showed multiple fungal elements in necrotic areas consisting of irregularly branched, hyaline septate hyphae having swollen cells, and occasional yeastlike cells. The use of Fontana-Masson silver stain showed the presence of melanin in cells walls and septa of the hyphae. Phialemonium obovatum was isolated when the ground tissue from disk and bone from L3-4 was cultured on biphasic brain-heart infusion medium. Colonies were moist, off-white to ochraceous with a characteristic green, diffusible pigment on the reverse side. The isolate grew well up to 40 degrees C. It formed characteristic adelophialides without conspicuous collarettes and basal septa and produced smooth, one-celled, hyaline, and obovate conidia. PMID- 8343051 TI - Plasma cell leukemia presenting as a pancreatic mass. AB - A 62-year-old woman presented with a 3-week history of obstructive jaundice. Computed tomography of the abdomen showed marked enlargement of the head of the pancreas and a prominent pancreatic body, suggestive of a neoplasm with associated pancreatitis. The peripheral blood showed an increased number of plasma cells accounting for 50% of the leukocytes. Biopsy specimens of the pancreas, liver, and a peritoneal lymph node showed a diffuse infiltrate of typical and atypical plasma cells (50% of which had cytoplasmic IgG-lambda). Serum and urine protein electrophoresis revealed a monoclonal IgG-lambda spike and Bence Jones-lambda protein, respectively. The bone marrow was diffusely infiltrated by plasma cells. To our knowledge, this is the first reported case of a plasma cell leukemia presenting as a pancreatic mass producing extrahepatic biliary obstruction. PMID- 8343052 TI - Adnexal tumor and a pigmented nevoid lesion in a benign cystic ovarian teratoma. AB - We describe a case of an unusual adnexal lesion and concurrent collections of dendritic melanocytes of the type occurring in a blue nevus in a mature cystic teratoma of the ovary. To our knowledge, there have been no previous reports of benign skin adnexal tumors in an ovarian dermoid cyst. This rarity would indicate that the cutaneous adnexal tissue in a benign teratoma is not unduly prone to undergo further more-specialized secondary tumorigenesis. The combination of the three benign lesions is therefore probably purely coincidental. PMID- 8343053 TI - Fusiform dilatations of the esophagus secondary to protracted distention and emetogenic injury. AB - We report the case of a 74-year-old woman who presented with a 2-year history of dysphagia, weight loss, nausea, and vomiting. She was diagnosed as having secondary achalasia due to external compression probably by a tumor of the lower part of the esophagus. At autopsy, however, no tumor was found at that site, whereas a pancreatic microcystic serous adenoma and multiple gastric leiomyomata- one of which occupied the pyloric sphincter area leading to gastric outlet obstruction--were noted. The esophagus displayed two fusiform dilatations located at the lower and midportions, the latter being associated with rupture and necrosis of the muscularis and adventitial wall layers. The lower dilatation showed only attenuation of the muscularis, without necrosis. The epithelium was intact in both dilatations. This was an unusual series of pathogenetic events, leading from gastric outlet obstruction to secondary achalasia and protracted vomiting, followed by spontaneous partial esophageal wall rupture (a variant of intramural hematoma) or atrophy of the muscularis, morphologically evident as fusiform dilatations. PMID- 8343054 TI - Lymphoproliferative process with natural killer cell phenotype. Histopathologic, ultrastructural, and surface marker observations. AB - We describe the clinical, structural, and immunophenotypic characteristics of a lymphoproliferative process characterized by persistent thrombocytopenia and prominent involvement of the spleen and, to a lesser degree, the liver. The proliferating cells lacked cytoplasmic azurophilic granules by light microscopy and on ultrastructural examination displayed prominent interdigitating cell processes and did not contain parallel tubular arrays. Immunophenotypically, the cells displayed markers of true natural killer cells (positive CD2, CD56, CD45, CD7, CD16, and CD33). No involvement of peripheral blood or bone marrow was detected. This case represents a proliferation of true natural killer cells probably arising in the spleen. The relationship of this process to other lymphoid proliferations at different sites with true natural killer cell or natural killer-like activity is unknown. PMID- 8343055 TI - Delayed sequelae of penetrating cardiac injury. AB - OBJECTIVE: We studied delayed or residual manifestations of penetrating cardiac injury in patients to determine the incidence, type, management, and outcome. BACKGROUND: Penetrating cardiac injury is associated with a high mortality despite improvement in management in recent years. Secondary lesions that are usually not looked for at the time of initial surgery are diagnosed and repaired postoperatively. DESIGN: Retrospective study. SETTING: The study was conducted at a major urban trauma center. PATIENTS: Forty-eight survivors of 71 penetrating cardiac injuries were treated during a 10-year period from 1980 to 1990. RESULTS: Delayed sequelae were diagnosed in 11 patients (23%) during the postoperative period. There were five ventricular septal defects, two aortic valvular injuries, one atrial septal defect, two conduction defects, and one tricuspid valvular lesion. All lesions were repaired electively with 100% survival. CONCLUSION: We found residual or delayed sequelae in 23% of our patients. Close follow-up and utilization of diagnostic studies, including two-dimensional echocardiography during the early postoperative period, can identify late sequelae and allow elective repair. PMID- 8343056 TI - Splenic abscess in the intensive care unit. AB - BACKGROUND AND METHODS: From 1980 through 1990, nine patients developed de novo splenic abscess during their stay in our intensive care unit (ICU), representing the first series of such reported cases. RESULTS: All nine patients were septic prior to the diagnosis of splenic abscess. The signs and symptoms of splenic abscess commonly described in the literature were of little help in detecting this pathology in ICU patients. Mean +/- SD platelet count, however, increased significantly, from 274 x 10(9)/L +/- 50 x 10(9)/L at admission to 647 x 10(9)/L +/- 94 x 10(9)/L at diagnosis. At diagnosis, left pleural effusion was present in all patients. Only three patients had detectable left upper quadrant tenderness. Abdominal computed tomographic scans, when used, were diagnostic in all cases. All patients were treated by splenectomy; eight had a solitary abscess. Six abscesses were caused by enteric organisms, two by Staphylococcus aureus, and one by Streptococcus epidermidis. Eight patients (89%) had had the offending organism previously isolated from their blood or from another infected site. Mortality was 45%. CONCLUSIONS: Splenic abscess, although a rare clinical entity, does occur de novo in ICU patients and is associated with significant mortality. Unexplained thrombocytosis in a septic ICU patient with persistent left pleural effusion is suggestive of splenic abscess. Previous culture and sensitivity results are useful in guiding perioperative antibiotic choices. PMID- 8343057 TI - Ovarian neoplasms in children. AB - OBJECTIVE: To review the clinical presentation, treatment, and outcome in a series of children with ovarian neoplasms. DESIGN: A retrospective review of the medical records in a case series of 29 girls with ovarian neoplasms. The length of follow-up ranged from 6 months to 7 1/2 years and averaged 3.0 years in the girls with malignant tumors. SETTING: The patients were treated at a large referral children's hospital. PATIENTS: Twenty-nine girls with ovarian neoplasms were treated from 1976 to 1992. The average age of the patients was 10 years and ranged from 2 to 16 years. MAIN OUTCOME MEASURES: The principal outcomes examined were mortality and surgical morbidity. RESULTS: The most common presenting symptoms for these ovarian tumors in pediatric patients included chronic abdominal pain, an abdominal mass, or distention. Three girls presented with precocious puberty or hirsutism. In 27 cases, the tumor was a primary ovarian lesion. In two patients, the ovarian mass was the presenting finding for a stage IV non-Hodgkin's lymphoma. Seventeen tumors were benign and 12 were malignant. Tumors originating from the germ-cell line predominated (n = 17). Seven of the 10 ovarian malignant neoplasms were stage I at the time of diagnosis. All but one of the girls with malignant tumors received either adjunctive radiation therapy or multiple-agent chemotherapy. Two girls with sex cord/stromal cell tumors who presented with stage I disease ultimately developed widespread metastases. Both girls with large epithelial tumors survived. All of the girls with benign tumors and seven (70%) of 10 with malignant lesions survived. CONCLUSION: Ovarian tumors are unusual lesions in the pediatric population. Unlike in adults, such neoplasms generally originate from the germ-cell line. Whereas most ovarian tumors in girls are benign, some children have malignant tumors that are very aggressive and do not respond well to adjuvant therapy. In particular, malignant sex cord/stromal cell tumors, even when they present at an early stage, may behave unpredictably. PMID- 8343058 TI - Thymectomy for myasthenia gravis. AB - OBJECTIVES: To assess the change in clinical status of patients with generalized myasthenia gravis treated with thymectomy and to identify prognostic variables that may be of significance in optimizing patient selection. DESIGN: Retrospective review. Mean follow-up period was 41 months. SETTING: Large community hospital. PATIENTS: Thirty-seven patients (11 male and 26 female) with generalized myasthenia gravis who were referred for thymectomy if they were refractory to medical treatment or had a thymoma. This represents all patients undergoing thymectomy for myasthenia gravis between January 1982 and December 1991. INTERVENTIONS: Each patient underwent staging before and after thymectomy using a modified Osserman classification. Medication requirements were also recorded. All patients underwent transsternal thymectomy and complete mediastinal dissection. MAIN OUTCOME MEASURES: Changes in clinical stage and medication requirement before and after thymectomy; effect of patient age, sex, duration of disease, stage of disease, antibody status, histologic characteristics of the thymus, and duration of follow-up on outcome. RESULTS: Improvement after thymectomy was noted in all 37 patients. Complete remission was achieved in three patients (8%) and pharmacologic remission in 23 (62%). The remainder improved in stage, medication requirement, or both. Patients in preoperative stages IIb and IIc showed the greatest improvement. Age, sex, duration of disease, antibody status, histologic characteristics of the thymus, and duration of follow-up were not significant factors in assessing improvement. CONCLUSIONS: Transsternal thymectomy was found to be beneficial to all patients with generalized myasthenia gravis. Complete or pharmacologic remission was achieved in most patients (70%) following the procedure. Patients in preoperative stages IIb and IIc showed the greatest degree of postoperative improvement. PMID- 8343059 TI - Effect of lithium on incorporation of bromodeoxyuridine and tritiated thymidine into human parathyroid cells. AB - OBJECTIVE: To measure lithium chloride-stimulated incorporation of tritiated thymidine (3H-TdR) and bromodeoxyuridine (BrdU) by human parathyroid cells as an indicator of lithium's growth-promoting properties. DESIGN: Cell suspensions derived from abnormal human parathyroid tissue were incubated for 5 days with graded concentrations of lithium and pulsed with either 0.074 MBq of 3H-TdR or 0.6 microgram of BrdU. The 3H-TdR incorporation was measured by counting cell filtrates in a beta counter, and nuclear BrdU incorporation was determined by counting nuclei positively stained by an antibody to BrdU. Counts of BrdU positive cells by two observers unaware of incubation conditions were correlated with 3H-TdR counts. RESULTS: Cell suspensions derived from adenomatous and hyperplastic parathyroid glands demonstrated a dose-related increase in 3H-TdR incorporation. There was close correlation between the two observers' counts of BrdU-positive cells (r = 0.70, P = .01) and between each observer's counts and 3H TdR counts (r = 0.70, P = .02, and r = 0.90, P = .01, respectively). CONCLUSIONS: Lithium stimulates in vitro incorporation of 3H-TdR and BrdU by abnormal human parathyroid cells, consistent with a growth-promoting effect. PMID- 8343060 TI - Preoperative pulmonary function evaluation for laparoscopic cholecystectomy. AB - OBJECTIVE: Hypercarbia with respiratory acidosis is a recognized complication of laparoscopic cholecystectomy. This study was performed to identify preoperatively those patients who may develop hypercarbia and acidosis during the procedure. DESIGN: Retrospective analysis of preoperative variables. PATIENTS: Thirty-one consecutive patients underwent laparoscopic cholecystectomy at one institution who were receiving both preoperative pulmonary function tests and arterial blood gas analysis. RESULTS: More than 80 demographic, laboratory, and perioperative variables were entered into a univariate analysis to identify predictors of intraoperative acidosis (pH, < 7.35). Patient age, duration of the procedure, and preoperative blood gas values were not predictors of intraoperative acidosis. Several univariant predictors for patients experiencing carbon dioxide pneumoperitoneum-induced hypercarbia were identified; these included an elevated American Society of Anesthesiologists classification and significant decreases in forced expiratory flow at 25% of maximum, maximal forced expiratory flow, maximal voluntary ventilation, vital capacity, inspiratory capacity, and diffusing capacity of the lung for carbon monoxide. CONCLUSIONS: This study suggests that neither age nor preoperative arterial blood gas values are predictive of intraoperative hypercarbia and acidosis during periods of carbon dioxide pneumoperitoneum. However, preoperative pulmonary function measures of decreased flow, limited capacity, and compromised diffusion do correspond to the development of intraoperative acidosis. Preoperative evaluation with pulmonary function tests demonstrating forced expiratory volumes less than 70% of predicted values and diffusion defects less than 80% of predicted values can identify those patients who are at risk of developing hypercarbia and acidosis. PMID- 8343061 TI - Prospective assessment of functional results after ileal J pouch-anal restorative proctocolectomy. AB - OBJECTIVE: To document the functional results of 50 consecutive patients who underwent hand-sewn ileal J pouch-anal restorative proctocolectomy for ulcerative colitis between 1988 and 1991 (mean follow-up, 18.1 months; range, 6 to 48 months). DESIGN: Patients recorded their observations daily over 1 week. The patients completed these weekly diaries every 3 months for the first year and then at 18, 24, 36, and 48 months after ileostomy closure. STUDY PARTICIPANTS: Fifty patients (mean age, 31 years; 24 males). SETTING: The University of Chicago (Ill). RESULTS: Stool frequency at 3, 6, 12, and 24 months was 6.3 +/- 2.1, 5.5 +/- 2.4, and 5.1 +/- 1.9, and 5.9 +/- 1.6 per day, respectively, without urgency. Fifty-four percent were perfectly continent; 18% had occasional spotting (one or two leaks per week); 12% had minor leakage (three to seven per week); and 16% had major leakage (more than seven per week). In these three groups, loss of solid feces never occurred in 84%, 88%, and 65% of patients, respectively. Females had more severe incontinence than males, but continence improved over time for both sexes. Twenty-two percent of female patients developed dyspareunia; no males developed impotence, but 19% had retrograde ejaculation. The probability of experiencing pouchitis increased with time from 15% at 6 months to 40% at 12 months, and 50% after 24 months. CONCLUSIONS: These results represent an accurate assessment of patient function after ileal J pouch-anal anastomosis. We encourage the use of a prospective, patient-completed protocol to obtain a realistic assessment of functional results. PMID- 8343062 TI - Transdiaphragmatic approach to the posterior mediastinum and thoracic esophagus. AB - OBJECTIVE: Complex operations involving the lower esophagus and posterior mediastinum are frequently compromised by poor exposure, thereby requiring combined thoracic and abdominal incisions. We describe our technique and report our experience with a transdiaphragmatic approach to the posterior mediastinum that improves exposure and eliminates the need for thoracotomies. PATIENTS: The lower thoracic esophagus and posterior mediastinum were exposed through a semicircular incision in the central tendon of the diaphragm. The indications for operation in 14 patients were benign conditions of the lower esophagus (reflux esophagitis, lye stricture, scleroderma, and achalasia) (n = 8), malignant neoplasm of the lower esophagus (n = 3), and revagotomy (n = 3). RESULTS: All indicated procedures, resections, and esophagogastric, esophagojejunal, or esophagocolonic anastomoses were completed through abdominal and/or cervical incisions. There were no thoracotomies performed. CONCLUSIONS: We believe this transdiaphragmatic approach greatly improves exposure to the lower and middle esophagus and posterior mediastinum compared with transhiatal approaches; preserves the integrity of the gastroesophageal junction; allows easy access to the vagus nerves without risking esophageal injury in patients who had undergone surgery previously; shortens operative time; and lessens pulmonary morbidity and decreases patients' pain and recovery time when compared with thoracotomy. PMID- 8343063 TI - Orotracheal intubation in trauma patients with cervical fractures. AB - OBJECTIVE: To evaluate orotracheal intubation with in-line stabilization of the cervical spine for emergency airway treatment of trauma patients with cervical spine injuries. DESIGN: Of 7518 trauma patients examined, 81 patients with cervical spine injuries received emergency orotracheal intubation. All intubations were performed by experienced anesthesiologists, with a separate individual maintaining in-line stabilization. Neurologic examination was documented before and after intubation. RESULTS: Peripheral neurologic deficit was present from the outset in 20 patients. There were unstable cervical fractures in 38 patients with no neurologic deficit. Twenty-three patients were neurologically intact with fractures that were later judged stable. In no instance was there a deterioration of neurologic status following intubation. Peripheral neurologic deficits improved after intubation in four patients. CONCLUSION: Orotracheal intubation, performed with manual in-line stabilization by trained and experienced personnel, is a safe emergency procedure in patients with cervical fractures. PMID- 8343064 TI - Intermittent sequential pneumatic compression in prevention of venous stasis associated with pneumoperitoneum during laparoscopic cholecystectomy. AB - OBJECTIVES: To determine whether pneumoperitoneum and reverse Trendelenburg's position used during laparoscopy impede common femoral venous flow and whether calf-length intermittent sequential pneumatic compression (ISPC) overcomes this impedance. DESIGN: Using Doppler ultrasonography, peak systolic velocities in the common femoral vein were measured in patients undergoing laparoscopic cholecystectomy with peritoneal insufflation of carbon dioxide. Measurements were obtained during three intervals: preoperatively with the patients in the supine position; after induction of general anesthesia with the patients in the supine position; and after insufflation to 13 to 15 mm Hg with the patients in the 30 degrees reverse Trendelenburg position (both with and without ISPC). Mean arterial pressure and heart rate were obtained concurrently. Measurements of preoperative and postoperative calf and thigh circumferences were obtained. SETTING: A tertiary care center. PATIENT PARTICIPANTS: A consecutive sample of 20 patients 30 to 70 years of age (15 women and five men) who underwent laparoscopic cholecystectomy and met the inclusion criteria. MAIN OUTCOME MEASURES: Peak systolic velocity, mean arterial pressure, heart rate, and calf and thigh circumferences. RESULTS: The combination of pneumoperitoneum to 13 to 15 mm Hg and a 30 degrees reverse Trendelenburg position significantly decreased peak systolic velocity in the common femoral vein from a preoperative mean of 0.24 +/- 0.025 m/s to 0.14 +/- 0.011 m/s, or a 42% decrease. Intermittent sequential pneumatic compression reversed that effect, returning peak systolic velocity to 0.27 +/- 0.021 m/s. The mean difference between preoperative peak systolic velocity and peak systolic velocity with a combination of pneumoperitoneum, reverse Trendelenburg's position, and ISPC was 0.03 +/- 0.03 m/s but was not significant. Anesthesia alone caused a mean increase in preoperative peak systolic velocity from 0.24 +/- 0.025 m/s to 0.3 +/- 0.032 m/s. Mean arterial pressure levels, heart rate, and calf and thigh circumferences did not change significantly. CONCLUSIONS: This study demonstrated a significant reduction in common femoral venous flow during laparoscopic cholecystectomy coincident with pneumoperitoneum and reverse Trendelenburg's position. Intermittent sequential pneumatic compression reversed that effect, returning peak systolic velocity to normal. PMID- 8343065 TI - Endotoxin stimulates lymphocyte glutaminase expression. AB - BACKGROUND/HYPOTHESIS: Glutamine is the principal fuel used by lymphocytes. It is hydrolyzed by the glutaminase enzyme, which regulates the rate of intracellular glutamine metabolism. Since lymphocyte glutamine utilization is increased during infection to support cellular proliferation, we hypothesized that endotoxin regulates lymphocyte glutaminase expression at the molecular level. METHODS: Adult rats received Escherichia coli endotoxin (one dose of 7.5 mg/kg) or saline. Total RNA from lymphocytes in the ileocolic lymph node chain was extracted for Northern hybridization and labeled with an alpha-phosphorus 32 rat glutaminase cDNA probe. The mRNA of the constitutively expressed gene beta-actin was the control for RNA loading. Quantitation of glutaminase transcripts was determined by densitometric scanning and values were normalized to actin. Glutaminase specific activity (nanomoles per milligram of protein per hour) and glutaminase kinetic parameters were also determined. RESULTS: Treatment with a single dose of endotoxin resulted in a 53% increase in glutaminase activity at 4 hours. Kinetic analysis showed that the increase in glutaminase activity was due to an 84% increase in Vmax (maximal enzyme velocity) with no change in Km (enzyme affinity). Endotoxin increased glutaminase mRNA twofold at 2 hours and more than fourfold at 4 hours. The increase in message preceded the increase in activity consistent with gene transcription prior to enzyme biosynthesis. CONCLUSION/CLINICAL RELEVANCE: The increase in glutaminase activity provides lymphocytes in the mesenteric lymph nodes with more glutamine for energy and cellular proliferation during times of infection when the gut mucosal barrier may become compromised. PMID- 8343066 TI - The history of the surgical treatment of portal hypertension. PMID- 8343067 TI - Suppression of proliferation of a human B-cell leukaemic cell line derived from acute lymphoblastic leukaemia by soluble factor(s) from Campylobacter rectus. AB - Soluble sonic extracts of several strains were examined for their ability to alter proliferation of a cell line derived from acute lymphoblastic leukaemia (BALL-1). Extracts of all strains tested caused dose-dependent suppression of proliferation when assessed by DNA (tritiated thymidine incorporation), RNA (tritiated uridine incorporation) and protein (tritiated leucine incorporation) synthesis. There was no effect on the viability of BALL-1 as measured by either trypan-blue exclusion or extracellular release of the cytoplasmic enzyme lactate dehydrogenase. The suppressive factor(s) was separated in a well-defined peak by high-pressure liquid DEAE ion-exchange chromatography, which revealed a single active peak with a molecular mass of 48 kDa. Characterization of the peak indicated that the suppressive factor(s) was heat labile (activity destroyed at 80 degrees C) and sensitive to the proteolytic enzyme pronase P. The soluble suppressive factor(s) from Campylobacter rectus thus has protein-like properties and no cytotoxicity to a human B-cell leukaemic cell line. PMID- 8343068 TI - The effect of growth on collagen and glycosaminoglycans in the articular disc of the rat temporomandibular joint. AB - Newly synthesized collagen and glycosaminoglycans (GAG) were studied in the temporomandibular discs of male Sprague-Dawley rats of 3-13 weeks of age. Each age group had eight animals and [14C]glycine or [3H]glucosamine were used to determine the proportion of newly synthesized type III to type I collagens or the proportion of different types of newly synthesized GAGs during 4 h of labelling in organ culture. Separation of newly synthesized collagen bands from rat disc by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed a peak in type III at the ages of 7 and 8 weeks. Type III collagen synthesis and the rate of mandibular growth were strongly related through all ages studied. GAG chains were separated by cellulose-acetate electrophoresis. Calculation of disintegrations/min per mg of wet disc tissue for each GAG peak showed that hyaluronic acid (HA), chondroitin-6-sulphate and keratan sulphate/chondroitin-4 sulphate (KS/C4S) were the predominant molecules synthesized in the disc. There was also a steady increase in newly synthesized HA and C6S synthesis up to 6 and 7 weeks respectively. Proportions of newly synthesized C4S/KS, HA and C6S were significantly higher than those of other GAGs with respect to ageing. From these observations it appears that the articular disc shows more of the characteristics of cartilage, as evidenced by the increased amounts of C6S and KS/C4S during the mandibular growth spurt at the ages of 6 and 7 weeks, similar to that of type III collagen. There were also increased amounts of HA, suggesting that during 5-7 weeks of age the rat disc is undergoing more active remodelling. This study provides baseline data for further analysis of the effects of mechanical loading and trauma on articular disc responses. PMID- 8343069 TI - Difference in chewing patterns between involved and opposite sides in patients with unilateral temporomandibular joint and myofascial pain-dysfunction. AB - Surface electromyograms (EMG) during maximal clenching and gum and peanut chewing were recorded from the temporal and masseter muscles of 30 patients with unilateral temporomandibular joint and myofascial pain-dysfunction (TMD). The gum chewing integrated EMGs were transformed to a differential Lissajous EMG figure (DL-EMG) to facilitate comparison of mastication on the dysfunctional and opposite side. Variables, mainly those in the gum-chewing DL-EMG, were statistically analysed, and were compared with those of normal subjects. Patients were then classified into three types: (1) same side, (2) opposite side and (3) intermediate side. Same-side patients chewed peanuts on the dysfunctional side, although this side did not necessarily show abnormal behaviour during gum chewing. Opposite-side patients chewed peanuts by avoiding the dysfunctional side and showed excellent chewing activity on the side opposite the dysfunction. Intermediate-side patients had a chewing pattern that was a combination of the first two types. The relation between the pain side, the preferred or habitual mastication side, and the side showing better mastication in the EMG pattern was shown to be important in research on the origin of TMD syndromes. It was speculated that in the same-side patients, overwork on the side with the better dental condition for chewing was the main cause of the dysfunction, and that so called hyperactivity on the dysfunctional side in TMD patients may result from habitual unilateral mastication. PMID- 8343070 TI - Glucose clearance from different surfaces of human central incisors and first molars. AB - The study examined the glucose clearance (retention) in saliva at different surfaces of these teeth in 23 subjects. The mouth was thoroughly rinsed for 15 s with 20 ml of a 0.5 M glucose solution. The concentrations of glucose absorbed by small pieces of paper, placed on the mesial, distal, labial (buccal), lingual and occlusal surfaces 3 min after rinsing, were measured using an immobilized enzyme system and an electrochemical sensor. On the maxillary and mandibular central incisors, the glucose concentrations on the labial surfaces were significantly higher than on all other surfaces and lowest on the lingual surfaces. In the mandibular molars, glucose concentrations were significantly higher on the buccal surfaces than on the lingual surfaces. Clear site-specific differences in glucose clearance were thus observed at the different tooth surfaces. It is considered that the differences in the glucose retention rate might be indicative of factors important for the site specificity of dental caries. PMID- 8343071 TI - A three-dimensional, finite-element analysis of bone around dental implants in an edentulous human mandible. AB - The design of dental superstructures influences the loading on dental implants and the deformation of the anterior interforaminal bone in an edentulous mandible. This deformation causes stress in the bone around the implants and may lead to bone resorption and loss of the implant. The stress distribution around dental implants in an edentulous mandible was calculated by means of a three dimensional, finite-element model of an entire lower jaw. This model was built from data obtained from slices of a single human mandible and was provided with two endosseous implants in the interforaminal region. The implants were either connected with a bar or remained solitary, and were loaded with a horizontal bite force of 10 N, a vertical bite force of 35 N, or an oblique bite force of 70 N. The most extreme principal stresses in the bone were always located around the neck of the implant. Stress around the implant was, therefore, not only caused by the local deformation of the bone due to movement of the implant and interface relative to the surrounding bone but also by the bending of the mandible. The most extreme principal stress was found with oblique bite forces. The highest maximum and lowest minimum principal stresses were 7.4 and -16.2 MPa in the model without the bar and 6.5 and -16.5 MPa in the model with the bar. When differences in the amount of bite force were eliminated, the vertical bite force resulted in the lowest stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343072 TI - An electromyographic study of whether the digastric muscles are controlled by jaw closing proprioceptors in man. AB - Whether in the oral system the digastric muscles (which lack muscle spindles) are under the control of proprioceptive information from the masseter muscles (which contain muscle spindles) was investigated by analysing whether and how the masseters and digastrics showed coordinated behaviour during a static, forceful bite. Subjects were asked to maintain a 100-N force for 15 s with and without visual guidance; bite force exerted, and masseter and digastric electromyograms (EMGs) were recorded. Under visual guidance all subjects co-contracted their digastric muscles during the isometric bite. They held the force for a short time, followed by periods with fluctuations (peak-to-peak force amplitude about 15-20 N). Fluctuations in bite force correlated with the masseter EMGs, the maximum in the correlogram occurring at about -50 ms with the force lagging the masseter. In 75% of the subjects a significant periodic component in the masseter and in the force spectra was found at about 4 Hz. This was also seen in the amplitude spectra of the forces, which showed in 80% of the subjects a significant elevation between 7-10 Hz as well. No correlation between the digastric EMGs and the bite forces, and between the EMGs of masseter and digastric could be detected. Spectra of digastric EMGs showed no prominent maxima. When subjects were deprived of visual feedback, maxima at -50 ms in the cross-correlation functions of the masseters and the forces were reduced considerably; periodicities of +/- 250 ms disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343073 TI - Urease activity in Streptococcus salivarius at low pH. AB - Arginine metabolism to alkali by the arginine deiminase system in oral bacteria increases their acid tolerance. The potential of urease activity in Streptococcus salivarius to fulfil a similar role was examined. In cell extracts between pH 5.0 and 8.0, urease activity was over 80% the maximal rate. The urease rate was zero at pH 4.3, and at pH 3.6 the enzyme was rapidly inactivated (t 1/2 of 0.6 min). The pH range of intact cells was broader. In Strep. salivarius cells acidified to pH 2.6 for 5 min, urease was completely retained and the ureolytic pH rise was rapid. There was no urease activity after acidification to pH 2. In cells acidified to maintain the pH between 3.3 and 4, viability was maintained for a short period (extrapolation indicated 20 min) and then decreased. This acidification induced alkali generation or acid removal that decreased in parallel to loss of viability. A small fraction (10%) of the urease was rapidly inactivated, after which both the remaining urease and pH response decreased at a similar rate to cell viability (t 1/2 of 15-20 min), but for at least 1 h following acidification, a rapid ureolysis induced rise in pH to above 7. In cells held at pH 3.6 and treated to compromise their membranes by freeze-thawing or transient acidification to pH 2.3, 70-80% of the urease was lost rapidly and the remainder inactivated at a rate similar to that in intact cells. Therefore, although at pH below 4, S. salivarius urease is outside its pH activity range and the free enzyme is rapidly inactivated, intact cells the urease is protected and ureolytic generation of ammonia is capable of substantially raising the pH for at least 1 h while the cell population is being progressively killed by acid. PMID- 8343074 TI - Air blast-induced evaporative water loss from human dentine, in vitro. AB - Short air blasts are commonly used to test for dentine sensitivity but their mechanism of action is poorly understood. In this study, evaporative water loss of teeth in vitro was measured under spontaneous conditions and during air blasts from three-way dental air syringes. Air blasts induced a 15-30-fold increase in evaporative water loss, which varied inversely with distance from the tooth and directly with air temperature. As water evaporation occurs readily across smear layers, which greatly impede bulk fluid movement, the use of air blasts may overestimate dentine sensitivity. Sustained air blasts may remove enough fluid from the pulp-dentine complex to cause disruption of odontoblasts and changes in pulpal blood flow. PMID- 8343075 TI - Presence but not synthesis of thyrotrophin-releasing hormone in rat salivary glands detected by radioimmunoassay and northern blot analysis. AB - Thyrotrophin-releasing hormone (TRH) is one of the ubiquitous peptides first isolated from hypothalamus. This study sought to examine if it could also be detected in rat submandibular salivary glands, as can other neurogastrointestinal peptides. Radioimmunoassay of submandibular gland homogenates revealed TRH-like immunoreactivity in all samples from male rats (637.34 pg/gland +/- 166.17, n = 15). In contrast, Northern blot analysis to determine whether the peptide was locally synthesized in the glands failed to detect TRH mRNA. Consequently, the presence of TRH in the glands (as revealed by radioimmunoassay) could be associated with binding to presumptive TRH receptors in the mediation of physiological activities. PMID- 8343076 TI - Effect of tooth temperature on activities of slowly adapting periodontal mechanoreceptors during or after long-lasting strong pressure applied to the cat upper canine tooth. AB - Periodontal mechanosensitive units (PM units) responsive to mechanical stimulation of this tooth were recorded from single fibres isolated from the superior alveolar nerve. Mechanical stimulation was applied in a sequence of long lasting strong pressure followed by a train of weak stimuli. Temperature was changed by perfusing the pulpal cavity of the stimulated tooth with saline solution at a temperature of 5-45 degrees C. The response of the PM units elicited by strong pressure was initially dynamic and subsequently static. The dynamic response was little affected by tooth temperature whereas, the static response increased with the rise in temperature. After strong pressure the excitability of the PM units was depressed transiently, followed by gradual recovery; this depression was especially prominent when tooth temperature was high. PMID- 8343077 TI - Absence of interaction between the 165-kDa fibronectin-binding protein involved in mouse odontoblast differentiation and vinculin. AB - Previous data suggested that matrix could control the organization of microfilaments in differentiating odontoblasts and that this process involved a complex of fibronectin-165-kDa membrane protein-vinculin. The use of two different gel systems and microsequence analysis demonstrated that two distinct 165-kDa proteins interact, one with fibronectin and the other with vinculin. PMID- 8343078 TI - Click-evoked oto-acoustic emissions in 1036 ears of healthy newborns. AB - Click-evoked oto-acoustic emissions (EOAEs) were recorded in 1036 ears of healthy newborns and in 71 normal-hearing adult ears. Newborns aged between 3 and 238 h were examined in a separate but not silent room of the obstetric ward. The adults were tested in a quiet but not sound-treated room. The recordings were more difficult in the newborn than in the adult, which was mirrored in recording parameters such as the time required for measurement (up to 7 min in newborns vs. 1-2 min in adult ears). Recording was always successful in adults, while retests were necessary in 4% of newborns. Also the artefact-rejection level and the stimulus stability were more favourable in adults. Still, EOAE recording for screening purposes in newborns seems feasible. Response levels in newborns (range 1.6-38.6; mean 20.2 dB SPL) appear to be higher than in adults (range 2.7-20.6; mean 12.8 dB SPL). The overall prevalence of EOAEs in newborns amounted to 93.4% and appeared to be age related. It rises from 78% in ears from newborns younger than 36 h to 99% in ears of newborns older than 108 h. This rise may be related to the middle ear clearance of amniotic fluid in the first days post partum. The prevalence in newborns older than 3-4 days is comparable with the prevalence of 97.2% in adults. Therefore, newborns should not be screened before the age of 4 days. In search of an objective EOAE detection variable, the prevalence of EOAEs for different age groups was calculated for various criterion values of reproducibility. These prevalences were compared to subjectively scored EOAE prevalences in the same age groups. A reproducibility criterion of about 50% appears to be useful for mass screening in newborns. PMID- 8343079 TI - Effects of noise burst rise time and level on the human brainstem auditory evoked response. AB - An experiment was conducted to examine the effects of noise burst rise time and level on the human BAER. Noise burst levels included 15, 30, 45 and 60 dB nHL, with linear rise times of 0, 0.5, 1.25 and 2.5 ms. With increasing noise burst level, there is a decrease in wave V latency and an increase in peak amplitude. With increasing noise burst rise time, there is an increase in wave V latency and a decrease in wave V amplitude. The slope of the latency/intensity function increases with increasing rise time. The slope of the latency/rise time function increases with decreasing noise burst level. The change in wave V latency associated with changing rise time is less than the change in rise time for all experimental conditions. PMID- 8343080 TI - Correlations between presbyacusis and extrinsic noxious factors. AB - As part of the longitudinal gerontological and geriatric population study of 70 year-olds in Goteborg, Sweden, the possible correlation between presbyacusis and extrinsic factors affecting health in elderly persons was investigated. Participants from one cohort (F 01) were studied longitudinally at ages 70, 75, 79 and 85 years, and from another cohort (F 06) at age 70 years. A weak correlation between hearing loss and smoking, alcohol abuse and head trauma was found for men and between hearing loss and intake of pharmaceutical agents (especially salicylates) for women. PMID- 8343081 TI - The role of tuning curve variables and threshold measures in the estimation of sensory cell loss. AB - Auditory-evoked potential tuning curves were collected at six frequencies before and 30 days after various noise exposures in 363 chinchillas using a simultaneous masking paradigm. Traditional bivariate and multiple linear regression/correlation analyses were performed in an effort to determine the extent to which sensory cell damage could be estimated from a knowledge of audiometric and tuning curve variables. The results showed strong correlations between percent outer hair cell (%OHC) loss and permanent threshold shift (PTS) and between %OHC loss and the tuning curve variables Q10 dB and high- and low frequency slopes (SHF, SLF). The correlations were strongest between PTS and %OHC loss. However, the proportion of variability (r2) in %OHC loss attributable to variability in the predictor variable(s) (i.e., PTS) could be increased significantly by adding the Q10 dB of the tuning curve whose probe frequency was centered in the octave band length of the cochlea corresponding to the frequency at which the PTS occurred. The r2 values could be further increased by including audiometric and tuning curve variables from frequencies adjacent to the octave band being evaluated. PMID- 8343082 TI - Age-associated degeneration of backward masking task performance: evidence of declining temporal resolution abilities in normal listeners. AB - A backward masking paradigm was employed to investigate temporal resolution capabilities in normal-hearing subjects of increasing chronological age. Results have documented: (1) a 2-, 4-, 8-, and 11-fold decibel magnitude difference for averaged psychoacoustic functions when comparing data obtained from young adults to those of elderly listeners; (2) that backward masking function slopes become significantly steeper with age, especially at very short interstimulus intervals; (3) a significant interaction between age and target frequency; (4) a linear age associated decrement in presumed temporal resolution abilities, and (5) no significant target frequency difference nor any ear differences existed. Both end organ and central nervous system mechanisms were considered in explaining these findings. PMID- 8343083 TI - Recent developments in diagnosis of exotic disease at the Australian Animal Health Laboratory. PMID- 8343084 TI - Nutrient intake of horses in thoroughbred and standardbred stables. AB - Twenty-five Thoroughbred (TB) and 25 Standardbred (SB) stables were visited to determine their feeding practices. The ingredients of the main feed of the day for a mature gelding of average size in full training were weighted at each stable. Nutrient content of diets was calculated using published data for the individual ingredients. Results are expressed as mean +/- sd. The estimated body weight of TB horses was 493 +/- 34 kg and 437 +/- 32 kg for SB horses. There was considerable variation in diet composition and nutrient intake between stables. The TB trainers fed 11.0 +/- 2.4 kg and SB trainers 11.8 +/- 2.5 kg per day. The concentrate component of the diet weighed 7.8 +/- 1.6 and 7.7 +/- 2.3 kg for TB and SB stables, respectively, and the roughage component for TB horses 3.3 +/- 1.4 and SB horses 4.1 +/- 1.4 kg per day. The digestible energy intake of horses at TB stables was 129 +/- 29 MJ per day and at SB stables 132 +/- 31 MJ per day. Crude protein intake of TB horses was 1452 +/- 363 g and SB horses 1442 +/- 338 g per day. There were differences in some feeding practices at TB and SB stables. Standardbred trainers fed more roughage than TB trainers. Standardbred trainers fed chaffed lucerne (alfalfa) and cereal hays as the major roughage, whereas TB trainers fed more hay. The major hay type fed by TB trainers was lucerne, whereas many SB trainers preferred clover hay. Both trainers fed oats as the major grain, but TB trainers fed slightly more maize (corn) than SB trainers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343085 TI - Identification of galegine, an isoprenyl guanidine, as the toxic principle of Schoenus asperocarpus (poison sedge). AB - An isoprenyl guanidine, galegine, was isolated from the Western Australian sedge Schoenus asperocarpus (Cyperaceae). Synthetic galegine was shown to reproduce the clinical and pathological features of poisoning by this plant. Preliminary results suggest that the massive thoracic effusion observed in sedge poisoning is the result of a direct effect on pulmonary vascular permeability. PMID- 8343086 TI - Treatment with vitamins A, D and E did not reduce weight loss in transported cattle. AB - Two field trials using an injectable vitamin A, D and E solution conducted in the pastoral environment of northern Australia are described. It was found that treatment of lighter (< 150 kg) or heavier (> 372 kg) weight cattle did not reduce weight loss during road transport. These findings contradict anecdotal evidence of reduced weight loss during transport with the use of vitamins A, D and E. The lack of scientific basis for their use is discussed. PMID- 8343087 TI - Chlamydiosis in workers at a duck farm and processing plant. AB - An outbreak of chlamydiosis was investigated in workers at a duck farm and processing plant during winter 1989. Chlamydia psittaci was isolated from ducks, but there was little evidence of clinical chlamydiosis in the ducks. Serological tests showed that 76% of workers had been exposed to infection, 12% recently, 16% had not been exposed and 8% had inconclusive test results. There was a strong association (P < 0.05) between years of employment and exposure to infection. Infection appeared to be contracted during the first year of employment. Measures were implemented to reduce shed contamination and control rodents and wild birds. At the same time, ducks were medicated, the processing plant was modified, work practices were altered and workers were advised about chlamydiosis to reduce the risk of human infection. PMID- 8343088 TI - Efficacy of ivermectin jetting fluid against strike by some primary and secondary blowflies of sheep. AB - Merino sheep, which were hand jetted with ivermectin jetting fluid, and untreated sheep were challenged with larval implants of Lucilia cuprina, Lucilia sericata, Calliphora nociva and Chrysomya rufifacies at intervals of about 2 weeks from 6 to 16 weeks after treatment. Both Lucilia species produced strike rates of about 90% in untreated sheep; the respective rates were lower for Chr rufifacies (55%) and C nociva (60%). Strike rates for the treated group were about 17, 11, and 9% for L cuprina, L sericata, and Chr rufifacies, respectively. Only 1 implant site in the treated group was struck by C nociva. Treated sheep had significantly (P < 0.01) longer time to first strike than did untreated ones for each species of fly. L sericata, Chr rufifacies, and C nociva larvae implanted on treated animals had significantly (P < 0.05) longer time to first strike than did L cuprina larvae. PMID- 8343089 TI - Efficacy of ivermectin as a pour-on formulation for control of buffalo fly. PMID- 8343090 TI - Feeding practices in thoroughbred and standardbred racehorse stables. PMID- 8343091 TI - Anthelmintic activity of milbemycin oxime against adult and immature Uncinaria stenocephala in dogs. PMID- 8343092 TI - Experimental tunicamycin toxicity in cattle, sheep and pigs. PMID- 8343093 TI - Susceptibility of freshly-mulesed lambs to flystrike and the effectiveness of propetamphos as a wound dressing. PMID- 8343094 TI - Sheep-adapted Anaplasma marginale maintains virulence for cattle. PMID- 8343095 TI - Spironucleus muris in laboratory mice. PMID- 8343096 TI - Lack of association between abortion and blood ammonia and methaemoglobin concentrations in dairy cows grazing improved pastures on the Atherton Tableland. PMID- 8343097 TI - The efficacy of ivermectin topically applied to cattle for control of adult buffalo flies (Haematobia irritans exigua). PMID- 8343098 TI - Developmental issues in social-skills assessment and intervention with children and adolescents. AB - In recent years, social-skills training has become an increasingly common intervention. Recipients of skill training programs have included children of all ages as well as adults, yet relatively few systematic attempts have been made to incorporate developmental considerations into program design and evaluation. Developmental research indicates that significant normative changes take place during the preschool, grade school, and adolescent years in domains such as the complexity of children's social reasoning, the focus and duration of their peer interactions, the nature of peer-approved (and disapproved) behaviors, the organization of the peer group, and the extent and nature of peer influence. Although a full understanding of the impact that these developmental changes may have on the effectiveness of various social-skills interventions awaits future research, the potential implications are numerous. In this article, developmental changes in children's peer relationships are reviewed. The implications that these changes may have for the assessment of social skills, for the design of skill training programs, and for future research are discussed. PMID- 8343099 TI - Assessing acceptance and social skills with peers in childhood. Current issues. AB - This article reviews current strategies for assessing social skills with peers in childhood, highlighting contemporary unresolved issues in identifying children who need intervention, selecting target behaviors, and assessing treatment outcome. Sociometric measures of peer acceptance are also considered. Although many current measures of social skills have adequate evidence of reliability and convergent validity, assessment could benefit from (a) increased documentation that the content of measures assesses important skills in relating to peers, (b) improved methods for assessing social behavior in specific interpersonal situations, and (c) more empirical evidence that indirect assessment methods (self-report, peer assessment, and teacher report) and analogue observations reflect in vivo behavior. PMID- 8343100 TI - Social skills interventions for children. AB - Children who exhibit social skills deficits experience short-term, and often long term, negative consequences. Reasons for such deficits, which have treatment utility, are reviewed and a number of procedures for treating children's social skills deficits are examined. In this article, these procedures are categorized into one of three broad and somewhat overlapping treatment approaches: operant conditioning, social learning, or cognitive-behavioral procedures. Descriptions of specific treatment procedures are provided, along with an examination of the effectiveness data, to support the various approaches to enhancing children's social behavior. The research literature provides strong support for the use of operant and social learning techniques, particularly with preschool and elementary school children. PMID- 8343101 TI - Social-skills interventions with adolescents. Current issues and procedures. AB - During adolescence, the interpersonal interactions and behaviors necessary for successful social functioning become increasingly complex. In recent years, social-skills training with adolescents has made a variety of advances beyond basic skill acquisition toward techniques designed to promote generalization and maintenance of an effective interpersonal repertoire. This article reviews relevant empirical literature for current issues and procedures in social-skills training with adolescents, including use of social-skills interventions for a variety of adolescent populations and problems, use of innovative and promising intervention procedures, and issues regarding generalization and social validity of intervention procedures. PMID- 8343102 TI - Assessing and enhancing generalization and social validity of social-skills interventions with children and adolescents. AB - Generalization and social validity are necessary aspects of any applied behavior analytic endeavor. They are especially critical to social-skills training research and practice. Investigators have demonstrated the effectiveness of various learning theory-based interventions in teaching social skills to and increasing peer interactions of children with and without disabilities. However, development of a technology for reliably transferring these changes across different situations or ensuring their persistence over time has proven to be more problematic. From both a conceptual and empirical standpoint, this article reviews progress in and barriers to assessing and enhancing generality of social behavior change and its relationship to social validity. If progress is to be made, then it will be necessary to (a) distinguish between generalization and generality in developing and evaluating social-skills interventions; (b) expand the concept of social validity to give more emphasis to objective measurement of social skills, interventions, and outcomes; and (c) pursue a systematic analysis of generality- and durability-programming tactics. PMID- 8343103 TI - [Immunology of the mammary gland of cattle]. AB - A successful control of udder diseases in dairy cattle widely depends on the knowledge of the mammary gland immune functions. They are responsible not only for the self-protection of this organ but also for the supply of the newborn with immunoprotective substances of humoral and cellular character. In the mammary gland, selected immunology methods may be used in the diagnosis of both local and systemic function disorders. Such evaluation represents a necessary prerequisite for a possible treatment by immunomodulators. PMID- 8343104 TI - [The effect of parenteral administration of 25-hydroxycholecalciferol and 1 alpha hydroxycholecalciferol on the mineral concentrations in the blood of cows in late pregnancy]. AB - The effect of 1 - 3 intramuscular injections of the vitamin D3 metabolite 25 OHD3, synthetic 1 alpha-OHD3, and a combination of both on the plasma concentrations of calcium (Ca), inorganic phosphate (P(i)) and magnesium (Mg) was tested in 67 older dry dairy cows. Administering 4,0 mg 25-OHD3 reduced Ca and P(i) for some time while Mg blood levels remained constant. Injecting 210 micrograms 1 alpha-OHD3 plus 2.0 mg 25-OHD3 only brought a marked increase in P(i) concentrations, whereas 420 micrograms 1 alpha-OHD3 plus 4.0 mg 25-OHD3, and 350 micrograms 1 alpha-OHD3 alone significantly raised Ca and P(i) levels beginning on the 2nd day after injection and lasting for at least 6 days. These higher levels can be maintained by repeated injections. Another effect of injecting 1 alpha-OHD3 was to depress Mg blood levels, and a negative effect on the Ca and vitamin D3 metabolism is suggested which may cause hypocalcaemia when the effect of 1 alpha-OHD3 subsides. Metastatic calcifications of soft tissues were observed in some 1 alpha-OHD3-treated cows. PMID- 8343105 TI - [Does the administration of derivatives of vitamin D to dairy cows in late pregnancy for the prevention of parturient paresis affect the maternal-fetal mineral metabolism?]. AB - Intramuscular injection of 1 alpha-hydroxyvitamin D3 (with or without 25 hydroxyvitamin D3) to highly pregnant dairy cows caused a significant increase of ionized calcium in blood and of total calcium and inorganic phosphate with a concomitant decrease of magnesium in blood plasma 3,5 +/- 1,9 days later (resp. 12-48 h a.p.). This brought about a higher Ca level at parturition preventing parturient paresis. The changes of maternal mineral and vitamin D status had no effect on the mineral concentrations of blood in newborn calves. However, the increase in calcium and phosphate concentrations in maternal blood after injection was accompanied by an increase of the minerals in the amniotic fluid reflecting their strong reciprocal exchange. On the other hand, the composition of allantoic fluid showed no significant changes. Therefore, analysis of both fetal fluids does not refer to disorders of fetal mineral metabolism. As a consequence, there seems to be no potential risk of intoxication after a prepartal injection of the substances to the mother for their offspring. PMID- 8343106 TI - [Detection of toxin-producing types of Pasteurella multocida--a comparison of methods]. AB - 28 Pasteurella multocida strains were examined for production of toxin by 6 different methods. Identical results were obtained using a mice lethality test, a tissue cell culture assay and an ELISA. Different results were received with a dot-blot-immunoassay (1 strain), using a gene probe (6 strains) and a guinea pig skin test (8 strains). Corresponding differences were detected with 2 strains only. Tissue culture, ELISA and dot-blot-immunoassay are effective methods for the diagnosis of toxin-producing Pasteurella multocida strains. Animal experiments should be an exception. PMID- 8343107 TI - [The effect of different biotechnical measures on live and stillborn piglets of sows of different body condition and parity]. AB - In a single large pig production unit of 6000 breeding sows, seven groups of 100 sows each were formed at random on the 110th day of pregnancy. Each group was evaluated and divided according to body condition in three subgroups. The average parity in each subgroup was recorded. The groups were treated as follows: Group 1 received on the 113th day of pregnancy a 3 mg single intramuscular dose of alfaprostol. Group 2 received on the 113th day of pregnancy a 3 mg single intramuscular dose of alfaprostol, 24 hours later a single intramuscular dose of 10 IU of oxytocin. Group 3 received a single intramuscular dose of 10 IU of oxytocin after the birth of the first piglet. Group 4 received on the 113th day of pregnancy a 100 mg single intramuscular dose of prednisolone. Group 5 received on the 113th day of pregnancy a 0.2 mg single intramuscular dose of carbamylcholine. Group 6 received from the 110th day of pregnancy food consisting of 12% fiber, 3 kg per sow per day. Group 7 (control) received a 3 ml physiologic NaCl solution on the 114th day of pregnancy. The following parameter were evaluated: A: Number of live born piglets B: Number of intrapartum stillborn piglets As regard number of live born piglets no significant difference was seen between the experimental groups (1-6) and the control group (7). On the other hand showed the experimental group 1, 2, 5 and 6 significant lower incidence of intrapartum stillbirth when compared to the control (group 7). Within the groups the tendency was seen, that the sows with higher parity and body condition produced less numbers of live born and higher numbers of intrapartum stillborn piglets. PMID- 8343108 TI - [The helminth fauna of wild boars of the west Berlin forests]. AB - Samples of muscles and internal organs obtained from 96 wild boars in the forests of West Berlin between September 1989 and August 1990, were examined for helminths. Nine nematode species, Metastrongylus pudendotectus, M. salmi, M. confusus, M. apri, Physocephalus sexalatus, Ascarops strongylina, Globocephalus urosubulatus, Ascaris suum and Trichuris suis belonging to five families could be found. Larvae of Toxocara spp. were isolated from most of the enzymatically digested samples of the gastrointestinal tract. In a few cases juvenile forms of Cysticercus tenuicollis could be identified. Trichinella spiralis and trematodes were not found. The correlation between helminth infection and age and sex of the wild boars as well as time and site of shooting are discussed. PMID- 8343110 TI - Band 3 HT, a human red-cell variant associated with acanthocytosis and increased anion transport, carries the mutation Pro-868-->Leu in the membrane domain of band 3. AB - 1. We have studied band 3 HT, a human red-cell band 3 variant with increased M(r), which is associated with abnormal red-cell shape (acanthocytosis) and increased anion-transport activity. 2. We have shown that the increased M(r) does not result from the presence of the band 3 Memphis mutation, and that the variant band 3 is covalently labelled by 4,4'-di-isothiocyanato-1,2-diphenylethane-2,2' disulphonic acid (H2DIDS) less readily than normal. 3. cDNA cloning studies show that band 3 HT results from the mutation Pro-868-->Leu, and the possible significance of the mutation in the altered anion-transport activity and cytoskeleton binding properties of band 3 HT is discussed. PMID- 8343111 TI - Peptide glyoxals: a novel class of inhibitor for serine and cysteine proteinases. AB - A series of novel synthetic dipeptides, containing a C-terminal glyoxal grouping (-COCHO), have been tested as inhibitors against typical members of the serine- and cysteine-proteinase families. For example, the sequences benzyloxycarbonyl (Cbz)-Pro-Phe-CHO (I) and Cbz-Phe-Ala-CHO (II), which fulfil the known primary and secondary specificity requirements of chymotrypsin and cathepsin B respectively, have been found to be potent reversible inhibitors of their respective target proteinase. Thus I was found to inhibit chymotrypsin with a Ki of approximately 0.8 microM, whereas II exhibits a Ki of approximately 80 nm against cathepsin B. These Ki values are some 10-fold and 3-fold lower than those reported for the corresponding peptide-aldehyde inhibitors of chymotrypsin and cathepsin B upon which the peptidyl-glyoxals were fashioned. Unexpectedly, the sequence Cbz-Pro-Ala-CHO, which was designed to inhibit elastase-like proteinases, exhibited no inhibitory activity towards porcine pancreatic elastase, even when used at concentrations as high as 200 microM. PMID- 8343109 TI - Regulated exocytosis. PMID- 8343113 TI - Influence of Mg2+ on detection of somatogenic and lactogenic components of growth hormone-binding protein in mammalian sera. AB - We recently classified the growth-hormone (GH)-binding protein (GH-BP) in a wide range of mammalian [including human (h)] sera and reported the existence of a major lactogenic component in GH-BP of type-III sera (rabbit, horse, dog, pig and cat), based on the capacity of bovine (b) and ovine prolactin (PRL) to displace 125I-labelled human growth hormone (hGH) binding and on direct 125I-bPRL binding studies. In this study, we demonstrate the high degree of Mg2+ dependence of the binding of the classically lactogenic hGH and bPRL, but not that of the somatogenic bGH to various mammalian sera (types I-IV). Serum GH-BP was assayed using a previously described and validated charcoal-separation assay. 125I-hGH binding to rat, ovine, bovine, rabbit, horse, dog and human sera was enhanced 1.5 2.5-fold in the presence of 70 mM Mg2+. The Mg2+ effect was concentration dependent between 3.7 mM and 70 mM, causing a significant and proportional increase in 125I-hGH binding to serum. Like 125I-hGH, 125I-bPRL binding to type III sera was also Mg(2+)-dependent. In contrast, 125I-bGH binding to all types of serum GH-BP was not affected by Mg2+ concentrations of up to 35 mM, while 70 mM Mg2+ slightly, but significantly, reduced (by approx. 15%) bGH binding to rabbit serum. In keeping with the Mg(2+)-dependent stimulation of lactogenic hormone binding to GH-BP, 70 mM Mg2+ caused a shift to the left in the displacement curves of hGH and bPRL competing with 125I-hGH binding to rabbit, dog, horse and human sera, while the effects of the somatogens bGH and rabbit GH were shifted to the right. Scatchard analysis of hGH displacement curves with sera from various species yielded linear plots and revealed that Mg2+ significantly increased (2.3 3.0-fold) the affinity constants, but not the binding capacities. These results demonstrate the ability of changes in Mg2+ concentration to determine the degree of differential recognition of somatogens versus lactogens by serum GH-BP. It remains to be determined whether such bivalent cation effects may account, at least in part, for the growth retardation seen in Zn2+ or Mg2+ ion deficiencies. PMID- 8343112 TI - Rapid activation of hepatic glutaminase in rats fed on a single high-protein meal. AB - We report that hepatic glutaminase is rapidly activated in rats fed on a single high-protein (60% casein) meal. Rats previously fed on a normal-protein (15% casein) diet for 3-4 days were given a high-protein meal for 2 h. The high protein meal increased the rate of flux through glutaminase in intact liver mitochondria nearly 3-fold (20.6 +/- 1.7 nmol/min per mg of protein versus 7.5 +/ 2.9 nmol/min per mg of protein) at a P(i) concentration of 10 mM. The activation of flux through glutaminase by a high-protein meal involved an increased sensitivity of glutaminase to P(i), an activator of the enzyme. The Ka for P(i) was 1.0 mM and 24.1 mM in mitochondria from rats fed on the high-protein and normal-protein meals respectively. We measured the concentration of P(i) in the mitochondrial matrix and found that it did not differ in mitochondria from rats fed on the high-protein and normal-protein meals, suggesting that the effect of the high-protein meal on the P(i)-sensitivity of glutaminase was not due to a change in the distribution of P(i) across the mitochondrial inner membrane. Glutaminase activity was measured by using mitochondrial membranes from frozen thawed mitochondria. Glutaminase activity and its dependence on P(i) were similar for preparations from rats fed on high-protein and normal-protein meals. These findings show that hepatic glutaminase is stimulated rapidly by a high-protein meal. This is part of the physiological hepatic response to increased protein intake which permits the liver to cope with the influx of glutamine occurring at this time. PMID- 8343114 TI - Unusual reactivity of Tyr-7 of GSH transferase P1-1. AB - Reaction of human GSH transferase P1-1 (GSTP1-1) with diethylpyrocarbonate (DEPC) at pH 7.0 and 4 degrees C resulted in covalent modification of an equivalent of one histidine and one tyrosine residue per subunit, with loss of activity. Sequence analysis showed that His-71 and Tyr-7 were modified. Reference to the three-dimensional structure of GSTP1-1 [Reinemer, Dirr, Ladenstein, Huber, Lo Bello, Frederici and Parker (1992) J. Mol. Biol. 227, 214-226] shows that the modification of Tyr-7 is most likely to affect enzyme activity. Kinetic analysis of the DEPC modification of Tyr-7 in GSTP1-1 gave a k2 approx. 150 times that of a peptide comprising residues 1-11 of GSTP1-1. The reaction of Tyr-7 of GSTP1-1 with DEPC was poorly inhibited by 1 mM GSH (14%) or 10 microM S-hexylglutathione (18%). DEPC treatment of the enzyme altered the absorbance at 290 nm in second derivative spectra, suggesting that a significant amount of tyrosinate ion occurs in the enzyme. GSH, however, did not significantly alter the A290. The data provide the first evidence of unusual chemical reactivity of Tyr-7 and are consistent with its proposed role as a proton acceptor during catalysis. PMID- 8343115 TI - Chemical modification of GSH transferase P1-1 confirms the presence of Arg-13, Lys-44 and one carboxylate group in the GSH-binding domain of the active site. AB - GSH transferase P1-1 (GSTP1-1) was modified with group-specific reagents. Kinetic experiments demonstrated that inactivation of GSTP1-1 occurred upon reaction of one arginine residue per subunit with diacetyl, one lysine residue per subunit with 2,4,6-trinitrobenzene sulphonate, or one carboxylate group per subunit with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. All three inactivation reactions were inhibited by compounds known to bind at the GSH site of the enzyme but were unaffected by the electrophile 1-chloro-2,4-dinitrobenzene. N-terminal sequence analysis showed that Arg-13 was modified by diacetyl and that this modification was inhibited by GSH. Arg-11 was not modified. The lysine residue modified by 2,4,6-trinitrobenzene sulphonate and protected by S-octylglutathione was identified as Lys-44 by sequencing of tryptic peptides. The findings are in agreement with the involvement of Arg-13 and Lys-44 in binding of GSH, as determined from the crystal structure [Reinemer, Dirr, Ladenstein, Huber, Lo Bello, Frederici and Parker (1992) J. Mol. Biol. 227, 214-226]. The present data also implicate a single carboxylate in GSH binding, consistent with the involvement of Asp-98 of subunit B determined from the crystallographic study. The GSH-binding determinants of GSTP1-1 are compared using sequence similarity with those of GSTs of Alpha, Mu and Theta classes. PMID- 8343116 TI - Studies on secondary structure of caldesmon and its C-terminal fragments. AB - Evaluation of the secondary structure of caldesmon from c.d. spectra revealed that it contains 51% helix, 9% beta-strand and 40% of remainder structures. These values agree well with the predicted ones from amino acid sequence, assuming an extended chain structure for caldesmon. The estimates of the secondary-structure elements in C-terminal 34 kDa and 19 kDa fragments are: 11 and 12% helix, 22 and 20% beta-strand, 13 and 17% beta-turns and loops, and 54 and 50% of remainder structure respectively. The best fit of experimental data was obtained assuming the globular state of the fragments. On the basis of structural analysis and fragmentation by proteolytic and chemical cleavages the six-domain model of caldesmon is proposed. PMID- 8343117 TI - Parathyroid hormone transport effects and hormonal processing in primary cultured rat proximal tubular cells. AB - The development of satisfactory cell culture models for the study of parathyroid hormone (PTH)-induced inhibition of Pi transport has proven difficult. Using subcellular fractionation techniques we investigated the response of primary cultures of rat proximal tubular cells to PTH-(1-34). Specific binding of 125I bPTH-(1-34) occurred at 2 degrees C. After 5 min of rewarming, trypsin-releasable radioactivity decreased from 90 to 50%, indicating internalization of the ligand. Cell disruption, followed by density centrifugation with 17% Percoll either directly after binding at 2 degrees C or post-rewarming for 20 min, showed a shift of 125I label from the plasma membrane (5'-nucleotidase) to lysosomal fractions (beta-D-glucosaminidase), confirming the sequential occurrence of cell surface binding, internalization and transport to lysosomes of 125I-bPTH-(1-34). Reculture at 37 degrees C revealed steady accumulation of trichloroacetic acid soluble radioactivity in the medium, indicating degradation of 125I-bPTH-(1-34). Phosphate transport in the absence of sodium was minimal. Incubation of the cells with bPTH-(1-34) resulted in up to 50% inhibition of sodium-dependent phosphate transport. Prior phosphate depletion abrogated the response to PTH. PMID- 8343118 TI - Endothelins stimulate tyrosine phosphorylation and activity of p42/mitogen activated protein kinase in astrocytes. AB - Endothelins (ET-1, -2, -3) display pleiotropic activities, by signalling through G-protein-coupled membrane receptors. We show here that ET-1 and ET-3 stimulate within minutes the tyrosine phosphorylation of a 42 kDa protein (p42) in primary cultures of mouse embryo astrocytes, but not in any of two subclones of rat astrocytoma C6 cells. This effect, measured by anti-phosphotyrosine immunoblotting of cell extracts, was also observed in response to bradykinin, platelet-derived growth factor, the phorbol ester phorbol 12-myristate 13-acetate and the G-protein activator fluoroaluminate. Pretreatment of cells with pertussis toxin, which inactivates Gi/G(o) proteins, did not affect these responses. However, down-regulation of protein kinase C completely blocked the response to phorbol ester and fluoroaluminate and at least partially impaired the ET-1 stimulated phosphorylation of p42. We have identified p42 as p42mapk, a mitogen activated protein (MAP) kinase, on the basis of the following data: by sequential immunoblotting with antiphosphotyrosine and anti-MAP kinase antibodies, (i) similar kinetics are observed for p42 phosphorylation and the decrease in p42mapk electrophoretic mobility, likely corresponding to its tyrosine/threonine phosphorylation [de Vries-Smits, Boudewijn, Burgering, Leevers, Marshall and Bos (1992) Nature (London) 357, 602-604]; (ii) p42 and the shifted form of p42mapk co migrate on SDS/PAGE; (iii) the myelin-basic-protein kinase activity of p42mapk is stimulated by ET-1, in parallel with the tyrosine phosphorylation of p42. In conclusion, these findings strongly suggest that endothelins can stimulate the tyrosine phosphorylation and activation of p42mapk in astrocytes, via pertussis toxin-insensitive G protein and protein kinase C-dependent and -independent pathways. PMID- 8343119 TI - A type I collagen reporter gene construct for protein engineering studies. Functional equivalence of transfected reporter COL1A1 and endogenous gene products during biosynthesis and in vitro extracellular matrix accumulation. AB - A type I collagen reporter gene construct, designed to facilitate detailed analysis of the consequences of introduced structural and regulatory mutations on collagen biosynthesis and participation in the extracellular matrix, was produced by site-directed mutagenesis of the mouse COL1A1 gene. The reporter construct, pWTCI-Ile822, carried a single base change which converted the codon for amino acid 822 of the triple helix from methionine to isoleucine. This change allowed the reporter protein, [Ile822]alpha 1(I), to be distinguished from the wild-type alpha 1(I), and quantified, by its altered CNBr cleavage pattern. In mouse Mov13 cells, which synthesize no endogenous pro alpha 1(I), reporter chains associated with endogenous pro alpha 2(I), formed pepsin-stable triple helices and were secreted efficiently from the cell. The thermal stability of wild-type molecules and molecules containing the reporter [Ile822]alpha 1(I) chains was identical. The biosynthetic characteristics of wild-type and reporter chains were directly compared in stably transfected 3T6 cells. These cells did not make a distinction between reporter and endogenous alpha 1(I) chains, which were secreted from the cells at the same rate and were processed and deposited into the 3T6 cell in vitro accumulated extracellular matrix with equal efficiency. These data demonstrate that the helical sequence alteration in the reporter protein is functionally neutral and that the reporter construct, pWTCI-Ile822, is a suitable vector for the analysis of the biochemical effects of site-directed mutations in the putative COL1A1 functional domains. PMID- 8343120 TI - Two independently regulated Ca2+ entry mechanisms coexist in Jurkat T cells during T cell receptor antigen activation. AB - Receptor-mediated Ca2+ influx was studied in the human leukaemic T cell line, Jurkat. Stimulation of these cells through the T cell antigen-receptor complex with OKT3 (an antibody against the CD3 molecules of the T cell antigen-receptor complex), or inhibition of the endoplasmic reticular Ca(2+)-ATPase with thapsigargin, resulted in Ca2+ mobilization from intracellular stores and the activation of Ca2+ and Mn2+ entry. The rates of thapsigargin-induced Ca2+ and Mn2+ entry in Jurkat cells were 76% and 64% respectively of those observed after treatment of these cells with OKT3. The combined addition of thapsigargin plus OKT3 to Jurkat cells produced an enhanced effect on the sustained increase in the cytosolic free Ca2+ concentration that was greater than that obtained by addition of thapsigargin or OKT3 alone. The rates of Ca2+ and Mn2+ entry were increased to 119% and 112% respectively of the OKT3-induced rates. Taken together, these results suggest that the inositol 1,4,5-trisphosphate-sensitive Ca(2+)-pool dependent bivalent cation entry only accounts for 57% and 52% respectively of the total OKT3-dependent Ca2+ and Mn2+ entry, and that the rest is mediated by second messenger(s). Thus two separate pathways coexist in regulating Ca2+ entry in Jurkat cells during activation mediated through the T cell receptor. PMID- 8343121 TI - Use of superfused rat skeletal muscle for metabolic studies: assessment of pH by 31P n.m.r. AB - We developed a muscle superfusion system suitable for metabolic studies of small isolated rat muscle ex vivo in real time and in a non-destructive manner by n.m.r. spectroscopy. In order to determine biochemical stability of superfused extensor digitorum longus (EDL) muscle (from fasted 45 and 100 g rats), the energy state and the pH of muscle were continuously monitored by 31P n.m.r. spectroscopy. ATP and phosphocreatine remained stable during 2 h whatever the muscle size (20 or 45 mg). Neither metabolite was a sensitive probe of possible metabolic compartmentation within muscle under our experimental conditions. By contrast, the chemical shift of Pi by its sensitivity to pH was a discriminant factor in the assessment of muscle stability. Indeed, heterogeneity of pH was observed only in the 45 mg EDL muscle resulting from a core region with loss of glycogen. Together, these observations suggest deviations of energy metabolism to supply ATP. Consequently, pH may be considered as a new real-time criterion for monitoring a metabolic heterogeneity due to changes in energy metabolism of muscle preparations ex vivo. PMID- 8343122 TI - Calcium measurements with a new high-affinity n.m.r. indicator in the isolated perfused heart. AB - A new n.m.r. indicator, 1,2-bis-(2-[1-(hydroxycarbony)ethyl- (hydroxycarbonylmethyl)]amino-5-fluorophenoxy)ethane (DiMe-5FBAPTA), with a higher affinity for calcium (apparent Kd 46 nM, pH 7.2, 30 degrees C) than the parent 5FBAPTA chelator (Kd 537 nM, pH 7.1, 30 degrees C) has been used to measure the cardiac intracellular free Ca2+ ([Ca2+]i). DiMe-5FBAPTA was loaded into Langendorff-perfused ferret hearts maintained at 30 degrees C using the acetoxymethyl ester (AM) derivative. The intracellular concentration required to achieve an adequate signal-to-noise (S/N) ratio (> 10:1) for the n.m.r. spectra caused a similar reduction in developed pressure to that obtained using 5FBAPTA AM. The DiMe-5FBAPTA was used to estimate [Ca2+]i in diastole, through the calcium transient and at rest in the presence of the slow calcium channel blocker diltiazem. At a pacing frequency of 1.0 Hz, end-diastolic [Ca2+]i was 198 +/- 30 nM (n = 9), and reducing the pacing frequency to 0.2 Hz lowered [Ca2+]i to 89 +/- 13 nM (n = 5). Perfusion with diltiazem (100 microM) for 60 min lowered [Ca2+]i to 10 +/- 1 nM (n = 4) in unpaced hearts and to 94 +/- 24 nM (n = 4) in hearts paced at 1.0 Hz. The [Ca2+]i transient measured with DiMe-5FBAPTA was sharper and delayed compared with the transient measured previously with 5FBAPTA. Co-loading the two indicators provided evidence that the indicator with the higher Kd had a dominant effect on the end-diastolic [Ca2+]i. The lower values for end-diastolic [Ca2+]i obtained with DiMe-5FBAPTA are consistent with fluorescent indicator measurements. These observations suggest that perturbations of [Ca2+]i caused by the new indicator are less than those induced by 5FBAPTA. DiMe-5FBAPTA therefore represents a useful step in the development of 19F-n.m.r. calcium indicators. PMID- 8343124 TI - Digestion of damaged DNA by the T7 DNA polymerase-exonuclease. AB - We have investigated the 3'-5'-exonuclease activity of phage T7 DNA polymerase for its usefulness as an approach for the detection of lesions in DNA. Unlike the T4 DNA polymerase-exonuclease, which is commonly used to map the position and frequency of lesions in very small DNA fragments, T7 DNA polymerase-exonuclease is able to hydrolyse almost completely the large fragments from KpnI-restricted mammalian DNA. However, we found that the exonuclease was also able to hydrolyse DNA containing several kinds of lesions: cyclobutane pyrimidine dimers, thymine glycols, and mono-adducts of 4'-hydroxymethyl-4,5',8-trimethylpsoralen and 5' methyl-isopsoralen. Modifications of the reaction conditions did not significantly alter the extent of hydrolysis. These properties distinguish the T7 DNA polymerase-exonuclease from the T4 DNA polymerase-exonuclease and make the T7 DNA polymerase-exonuclease unsuitable for detecting several types of lesions in DNA. PMID- 8343123 TI - Mobilization of Ca2+ by thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone in permeabilized insulin-secreting RINm5F cells: evidence for separate uptake and release compartments in inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. AB - We characterized and directly compared the Ca(2+)-releasing actions of two inhibitors of endoplasmic-reticulum (ER) Ca(2+)-ATPase, thapsigargin and 2,5-di (t-butyl)-1,4-benzohydroquinone (tBuBHQ), in electropermeabilized insulin secreting RINm5F cells. Ambient free calcium concentration ([Ca2+]) was monitored by Ca(2+)-selective mini-electrodes. After ATP-dependent Ca2+ uptake, thapsigargin and tBuBHQ released Ca2+ with and EC50 of approximately 37 nM and approximately 2 microM respectively. Both agents mobilized Ca2+ predominantly from the Ins(1,4,5)P3-sensitive Ca2+ pool, and in this respect thapsigargin was more specific than tBuBHQ. The total increase in [Ca2+] obtained with thapsigargin and Ins(1,4,5)P3 was, on the average, only 7% greater than that with Ins(1,4,5)P3 alone. In contrast, the total increase in [Ca2+] obtained with tBuBHQ and Ins(1,4,5)P3 was 33% greater than that obtained with only InsP3 (P < 0.05). Although Ca2+ was rapidly mobilized by thapsigargin and tBuBHQ, complete depletion of the Ins(1,4,5)P3-sensitive Ca2+ pool was difficult to achieve. After the release by thapsigargin or tBuBHQ, Ins(1,4,5)P3 induced additional Ca2+ release. The additional Ins(1,4,5)P3-induced Ca2+ release was not altered by supramaximal concentrations of thapsigargin and tBuBHQ, or by Bafilomycin A1, an inhibitor of V-type ATPases, but was decreased by prolonged treatment with the ER Ca(2+)-ATPase inhibitors. These results suggest the existence of distinct uptake and release compartments within the Ins(1,4,5)P3-sensitive Ca2+ pool. When treated with the inhibitors, the two compartments became distinguishable on the basis of their Ca2+ permeability. Apparently, thapsigargin and tBuBHQ readily mobilized Ca2+ from the uptake compartment, whereas Ca2+ from the release compartment could be mobilized only very slowly, in the absence of Ins(1,4,5)P3. PMID- 8343125 TI - L(+)-Mandelate dehydrogenase from Rhodotorula graminis: purification, partial characterization and identification as a flavocytochrome b. AB - L(+)-Mandelate dehydrogenase was purified to homogeneity from the yeast Rhodotorula graminis KGX 39 by a combination of (NH4)2SO4 fractionation, ion exchange and hydrophobic-interaction chromatography and gel filtration. The amino acid composition and the N-terminal sequence of the enzyme were determined. Comprehensive details of the sequence determinations have been deposited as Supplementary Publication SUP 50172 (4 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1993) 289, 9. The enzyme is a tetramer as judged by comparison of its subunit M(r) value of 59,100 and native M(r) of 239,900, estimated by SDS/PAGE and gel filtration respectively. There is one molecule of haem and approx. one molecule of non covalently bound FMN per subunit. 2,6-Dichloroindophenol, cytochrome c and ferricyanide can all serve as electron acceptors. L(+)-Mandelate dehydrogenase is stereospecific for its substrate. D(-)-Mandelate and L(+)-hexahydromandelate are competitive inhibitors. The enzyme has maximum activity at pH 7.9 and it has a pI value of 4.4. HgCl2 and 4-chloromercuribenzoate are potent inhibitors, but there is no evidence that the enzyme is subject to feedback inhibition by potential metabolic effectors. The evidence suggests that L(+)-mandelate dehydrogenase from R. graminis is a flavocytochrome b which is very similar to, and probably (at least so far as the haem domain is concerned) homologous with, certain well characterized yeast L(+)-lactate dehydrogenases, and that the chief difference between them is their mutually exclusive substrate specificities. PMID- 8343126 TI - The Ca(2+)-transporting ATPases of rabbit and trout exhibit different pH- and temperature-dependences. AB - The phosphorylation of the trout sarcoplasmic-reticulum Ca(2+)-ATPase by Pi differs in its temperature- and pH-dependence from the rabbit ATPase. In the trout enzyme, the apparent affinity for Pi and maximum phosphoenzyme values do not vary over a pH and temperature ranges that have a pronounced effect on the rabbit enzyme. The lack of temperature-dependence for phosphorylation is observed at pH 6.8. At pH 8.0, the temperature profile for phosphorylation of the trout enzyme resembles that of the rabbit at pH 6.8. The rabbit ATPase is no longer phosphorylated by Pi after solubilization with the detergent C12E9. In contrast, the trout enzyme can be phosphorylated by Pi after solubilization with C12E9, and the same levels of phosphoenzyme were obtained with the soluble and membrane bound ATPase at both 0 degrees and 25 degrees C. In the range of 0-20 degrees C, the rates of ATP synthesis and of Ca2+ uptake by the trout ATPase are less temperature-dependent than for the rabbit enzyme. However, both isoenzymes catalyse ATP hydrolysis with similar temperature-dependences. The results raise the possibility that protonation of specific amino acid residues may contribute to the lack of temperature-dependence for phosphorylation of the trout Ca(2+) ATPase. PMID- 8343127 TI - Cytosolic and nuclear spermidine acetyltransferases in growing NIH 3T3 fibroblasts stimulated with serum or polyamines: relationship to polyamine biosynthetic decarboxylases and histone acetyltransferase. AB - The expression (mRNA level of enzymic activity) of cytosolic and nuclear spermidine acetyltransferases was studied in NIH 3T3 fibroblasts, either (1) serum-starved and stimulated to grow by serum refeeding, or (2) treated with inhibitors of ornithine decarboxylase (ODC) (MDL 72.175) and S-adenosylmethionine decarboxylase (AdoMetDC) (MDL 73.811) and stimulated to grow by spermidine. Expression of the known growth-regulated genes for ODC, AdoMetDC and histone acetyltransferase was also examined. The mRNA for spermidine/spermine N1 acetyltransferase (SAT) accumulated after serum refeeding (between 6 and 16 h) and even more after spermidine addition (16 h). Histone acetyltransferase activity increased after both growth stimuli, whereas spermidine N8 acetyltransferase activity remained unchanged. After serum stimulation, the ODC mRNA level and activity rose between 6 and 16 h, whereas AdoMetDC mRNA accumulation occurred later (16 h) than the increase in enzyme activity (6 h). Stimulation of ODC and AdoMetDC activities was suppressed by the inhibitors added alone or in combination with spermidine, whereas mRNA accumulation was down regulated by spermidine. These results indicate that the expression of SAT was growth-controlled and that SAT mRNA level was regulated by polyamines. PMID- 8343128 TI - Trichomonas vaginalis: characterization of ornithine decarboxylase. AB - Ornithine decarboxylase (ODC), the lead enzyme in polyamine biosynthesis, was partially purified from Trichomonas vaginalis and its kinetic properties were studied. The enzyme appears to be of special significance in this anaerobic parasite, since the arginine dihydrolase pathway generates ATP as well as putrescine from arginine. ODC from T. vaginalis had a broad substrate specificity, decarboxylating ornithine (100%), lysine (1.0%) and arginine (0.1%). The enzyme had a pH optimum of 6.5, a temperature optimum of 37 degrees C and was pyridoxal 5'-phosphate-dependent. Attempts to separate ornithine- from lysine decarboxylating activity by thermal-stability and pH-optima curves were not successful. Although Km values for ornithine and lysine were 109 and 91 microM respectively, and the Vmax values for these substrates were 1282 and 13 nmol/min per mg of protein respectively, the most important intracellular substrate is ornithine, since intracellular ornithine levels are 3.5 times those of lysine and extracellular putrescine levels are 7.5 times those of cadaverine. Ornithine was also an effective inhibitor of lysine-decarboxylating activity (Ki 150 microM), whereas lysine was relatively ineffective as inhibitor of ornithine decarboxylating activity (Ki 14.5 mM). Crude ODC activity was localized (86%) in the 43,000 g supernatant and 3303-fold purification was obtained by (NH4)2SO4 salting and DEAE-Sephacel, agarose-gel and hydroxyapatite chromatography steps. The enzyme bound difluoro[3H]methylornithine ([3H]DFMO) with a ratio of drug bound to activity of 2500 fmol/unit, where 1 unit corresponds to 1 nmol of CO2 released from ornithine/min. The enzyme had a native M(r) of 210000 (gel filtration), with a subunit M(r) of 55,000 (by SDS/PAGE), suggesting that the trichomonad enzyme is a tetramer. From the subunit M(r) and binding ratio of DFMO, there is about 137 ng of ODC per mg of T. vaginalis protein (0.013%). The significant amount of ODC protein present supports the view that putrescine synthesis in T. vaginalis plays an important role in the metabolism of the parasite. PMID- 8343129 TI - Cloning, in vitro mitochondrial import and membrane assembly of the 17.8 kDa subunit of complex I from Neurospora crassa. AB - We have cloned and sequenced a cDNA encoding a 17.8 kDa subunit of the hydrophobic fragment of complex I from Neurospora crassa. The deduced primary structure of this subunit was partially confirmed by automated Edman degradation of the isolated polypeptide. The sequence data obtained indicate that the 17.8 kDa subunit is made as an extended precursor of 20.8 kDa. Resistance of the polypeptide to alkaline extraction from mitochondrial membranes and the existence of a putative membrane-spanning domain suggests that the 17.8 kDa subunit is an intrinsic (bitopic) membrane protein. The in vitro synthesized precursor of the 17.8 kDa subunit can be efficiently imported into isolated mitochondria, where it is cleaved to the mature species by the metal-dependent matrix-processing peptidase. The in vitro imported mature subunit is found mainly exposed to the mitochondrial intermembrane space. However, a significant fraction of the imported polypeptide acquires the same membrane topology as the endogenous subunit, indicating that correct assembly in the mitochondrial inner membrane did occur. PMID- 8343130 TI - Non-catalytic activation of phospholipase C-gamma 1 in vitro by epidermal growth factor receptor. AB - To investigate the possible functional role of epidermal growth factor (EGF) receptor-phospholipase C-gamma 1 (PLC-gamma 1) complexes, we have measured PLC gamma 1 activity in vitro in the absence or presence of purified EGF receptor. Immunoprecipitates of PLC-gamma 1 from control A-431 cells were incubated without or with purified EGF receptor in the absence or presence of ATP. Under these conditions the EGF receptor increased non-tyrosine-phosphorylated PLC-gamma 1 activity 3-4-fold in the absence or presence of ATP, but increased tyrosine phosphorylated and activated PLC-gamma 1 by only 20-50%. Both basal and autophosphorylated forms of the purified EGF receptor increased the activity of the non-tyrosine-phosphorylated PLC-gamma 1, and stoichiometric levels of purified receptor were required to increase PLC activity. Other tyrosine kinases such as the platelet-derived growth factor receptor and erbB-2, but not the insulin receptor, also stimulated PLC-gamma 1 activity. PLC-gamma 1 activity could be activated with the kinase-negative EGF receptor, but a C-terminal truncated receptor was much less effective. Purified EGF receptor could also activate PLC-beta 1, but with a much decreased potency compared with PLC-gamma 1. Our results suggest that in vitro the EGF receptor can increase PLC-gamma 1 activity independently of tyrosine phosphorylation. PMID- 8343131 TI - Transgenic mice over-expressing the human spermidine synthase gene. AB - We have generated a transgenic mouse line harbouring the functional (chromosome-1 derived) human spermidine synthase (EC 2.5.1.16) gene in their genome. The transgenic animals expressed the human gene-derived mRNA, as revealed by reverse transcriptase/PCR analysis, in all tissues studied and displayed tissue spermidine synthase activity that was 2-6 times that in their syngenic littermates. The elevated spermidine synthase activity, however, had virtually no effect on tissue putrescine, spermidine or spermine levels. The view that the accumulation of spermidine and spermine is possibly controlled by S adenosylmethionine decarboxylase was further supported by the finding that tissue spermidine and spermine contents also remained practically normal in hybrid transgenic mice over-expressing both human ornithine decarboxylase and spermidine synthase genes. PMID- 8343132 TI - Calorimetric studies of the N-terminal half-molecule of transferrin and mutant forms modified near the Fe(3+)-binding site. AB - The effects of single amino acid substitution on the thermal stability of the N terminal half-molecule of human transferrin and its iron-binding affinity have been studied by high-sensitivity scanning calorimetry. All site-directed mutations are located on the surface of the binding cleft, and they are D63-->S, D63-->C, G65-->R, H207-->E and K206-->Q. Differential scanning calorimetry results show that the mutations do not significantly alter the conformational stability of the apo-forms of the proteins. The changes in free energy of unfolding relative to the wild-type protein range from 0.83 to -2.4 kJ/mol. The D63-->S, G54-->R and H207-->E mutations slightly destabilize the apo-protein, while the D63-->C and K206-->Q mutations increase its stability by a small amount. However, there are large compensating enthalpy-entropy changes caused by all mutations. All mutants bind ferric ion, but with different affinities. Replacement of Asp-63 by either Ser or Cys decreases the apparent binding constant by 5-6 orders of magnitude. The G65-->R mutation also decreases the apparent binding constant by 5 orders of magnitude. The K206-->Q mutation increases the apparent binding constant by 20-fold, while the H207-->E mutation does not significantly change the apparent iron-binding affinity of the half molecule. PMID- 8343133 TI - Inactivation of the endogenous argininosuccinate lyase activity of duck delta crystallin by modification of an essential histidine residue with diethyl pyrocarbonate. AB - The argininosuccinate lyase activity of duck delta-crystallin was inactivated by diethyl pyrocarbonate at 0 degrees C and pH 7.5. The inactivation followed pseudo first-order kinetics after appropriate correction for the decomposition of the reagent during the modification period. The plot of the observed pseudo-first order rate constant versus diethyl pyrocarbonate concentration in the range of 0.17-1.7 mM was linear and went through the origin with a second-order rate constant of 1.45 +/- 0.1 M-1.s-1. The double-logarithmic plot was also linear, with slope of 1.13, which suggested a 1:1 stoichiometry for the reaction between diethyl pyrocarbonate and delta-crystallin. L-Arginine, L-norvaline or L citrulline protected the argininosuccinate lyase activity of delta-crystallin from diethyl pyrocarbonate inactivation. The dissociation constants for the delta crystallin-L-arginine and delta-crystallin-L-citrulline binary complexes, determined by the protection experiments, were 4.2 +/- 0.2 and 0.12 +/- 0.04 mM respectively. Fumarate alone had no protective effect. However, fumarate plus L arginine gave synergistic protection with a ligand binding interacting factor of 0.12 +/- 0.02. The double-protection data conformed to a random Uni Bi kinetic mechanism. Fluorescence-quenching studies indicated that the modified delta crystallin had minimum, if any, conformational changes as compared with the native delta-crystallin. Inactivation of the enzyme activity was accompanied by an increasing absorbance at 240 nm of the protein. The absorption near 280 nm did not change. Treatment of the modified protein with hydroxylamine regenerated the enzyme activity to the original level. These results strongly indicated the modification of an essential histidine residue. Calculation from the 240 nm absorption changes indicated that only one histidine residue per subunit was modified by the reagent. This super-active histidine residue has a pKa value of approximately 6.8 and acts as a general acid-base catalyst in the enzyme reaction mechanism. Our experimental data are compatible with an E1cB mechanism [Raushel (1984) Arch. Biochem. Biophys. 232, 520-525] for the argininosuccinate lyase with the essential histidine residue close to the arginine-binding domain of delta crystallin. L-Citrulline, after binding to this domain, might form an extra hydrogen bond with the essential histidine residue. PMID- 8343134 TI - Effect of betaine on HSP70 expression and cell survival during adaptation to osmotic stress. AB - Induced expression of the HSP70 gene in 3T3 and SV-3T3 cells was monitored by measurements of the synthesis of HSP70 and of the cellular contents of both HSP70 and its mRNA. The presence of betaine (N-trimethylglycine) at concentrations of 2.5-25 mM decreased the induction of HSP70 gene expression caused by incubation of 3T3 and SV-3T3 cells in hypertonic (0.5 osM) medium. This effect was accompanied by an enhancement of SV-3T3 cell adaptation, assayed by colony formation, to the hyperosmotic conditions. In contrast, the presence of betaine did not affect HSP70 gene expression induced in these cells by heat shock. After 6 h incubation with 25 mM betaine under hypertonic (0.5 osM) conditions the intracellular concentration of betaine in SV-3T3 cells was about 195 mM, compared with about 70 mM under isotonic (0.3 osM) conditions. Hence, with this concentration of extracellular betaine, the marked increase in the accumulation of betaine within the cells presumably counteracts the imposed osmotic pressure and eliminates the signal that otherwise initiates increased expression of the HSP70 gene. PMID- 8343135 TI - Purification, characterization and binding interactions of the Chinese-cobra (Naja naja atra) serum antitoxic protein CSAP. AB - The characterization of the single-chain protein in Chinese-cobra (Naja naja atra) blood serum, which yields strong specific protection against the venom of the same snake, is reported. The protein, CSAP (cobra serum antitoxic protein), was purified to electrophoretic homogeneity. Over the pH range 5-9 it formed stable complexes with the neuro- and the cardio-toxin of the snake. The molecular size of the CSAP was estimated to be 70.3 +/- 0.3 kDa. Tryptic hydrolysis of CSAP yielded several peptides that were able to bind to the toxin. The native CSAP maximally bound 8 +/- 1 toxin molecules/molecule. Six tryptic fragments, containing 5-39 residues, were sequenced. The longest of these displayed sequence similarity to rat serum albumin. The protective effect of the CSAP was demonstrated in vivo on mice and in vitro by measurement of the rate of haemolysis. Kinetic and thermodynamic parameters of the binding interactions of the neurotoxin and the CSAP were determined from the rates of displacement of 125I-labelled toxin from its complexes with the CSAP by unlabelled toxin by using a DEAE-cellulose filter assay for CSAP-toxin complexes. The toxin molecules rapidly dissociated from one type of site and slowly from a second. The binding capacity and concentration of the CSAP suffice to explain the protective effect of the latter against the toxin. PMID- 8343136 TI - Binding of a substrate analogue can induce co-operative structure in the plasmin serine-proteinase domain. AB - Human miniplasminogen and miniplasmin were studied by n.m.r. spectroscopy and differential scanning calorimetry (d.s.c.) in order to investigate the structural properties of the serine-proteinase domain. The d.s.c. thermograms of both miniplasminogen and non-inactivated miniplasmin at pH 4.0 can be closely fitted to two transitions, at 62 +/- 2 and 72 +/- 2 degrees C, corresponding to unfolding of the kringle 5 and proteinase domains respectively. No evidence was found, under these conditions, for non-co-operative unfolding of the proteinase domain. On inactivation of miniplasmin with an affinity label, a number of additional resonances arising from residues of the proteinase domain are observed in resolved regions of the n.m.r. spectrum. A combination of variable-temperature n.m.r. and d.s.c. has shown that part of the proteinase domain undergoes a major conformational transition on heating which is distinct from the unfolding of the remainder of the proteinase domain or the kringle 5 domain. This additional transition occurs at a temperature that depends on the nature of the affinity label present and is not observed in the absence of an inactivating agent. These results provide direct evidence for the existence of a region of the proteinase domain which, under these conditions, becomes structured only in the presence of a bound substrate. PMID- 8343137 TI - Turnover of inositol pentakisphosphates, inositol hexakisphosphate and diphosphoinositol polyphosphates in primary cultured hepatocytes. AB - We have used a non-transformed cell model, the primary cultured hepatocyte, to explore the turnover of inositol hexakisphosphate, multiple isomers of inositol pentakisphosphate and two novel diphosphoinositol polyphosphates. All of these compounds gradually accumulated radioactivity throughout a 70 h period of labelling with [3H]inositol. However, a rapid metabolic rate was revealed upon inhibition of diphosphoinositol polyphosphate biphosphatase(s) with 1 mM fluoride for 40 min: this treatment elevated levels of [3H]diphosphoinositol polyphosphates up to 10-fold, indicating that their cellular pools were normally turning over at least 10 times every 40 min. This was accompanied by a turnover of about 10% of the pool of inositol hexakisphosphate. Control experiments established that 200 nM vasopressin brought about a typical activation of phospholipase C in hepatocytes after 62 h of primary culture. This agonist treatment did not affect steady-state levels of [3H]inositol pentakisphosphates, [3H]inositol hexakisphosphate or [3H]diphosphoinositol polyphosphates. However, prolonged treatment of hepatocytes with 2 microM thapsigargin reduced steady state levels of [3H]diphosphoinositol polyphosphates by 50-70%. This effect of thapsigargin was also observed in the presence of fluoride, indicating that thapsigargin inhibited the rate of synthesis of diphosphoinositol polyphosphates. PMID- 8343138 TI - Polarimetry and 13C n.m.r. show that the hydrolyses of beta-D-glucopyranosyl fluoride by beta(1-->3)-glucanases from Phanerochaete chrysosporium and Sporotrichum dimorphosporum have opposite stereochemistries. AB - The time courses of optical rotation and fluoride ion release during hydrolysis of beta-D-glucopyranosyl fluoride by the beta(1-->3)-glucanase of Phanerochaete chrysosporium (J. L. Copa-Patino and P. Broda, unpublished work) indicated that the initial sugar product was beta-D-glucopyranose. This was confirmed by monitoring the hydrolysis of 1-[13C]beta-D-glucopyranosyl fluoride by this enzyme with 13C n.m.r. (without proton decoupling). The same two techniques were used to confirm that hydrolysis of beta-D-glucopyranosyl fluoride by the exo beta(-->3) glucanase of 'Basidiomycete QM 806' (identified as Sporotrichum dimorphosporum) yielded alpha-glucopyranose as first sugar product, in accordance with previous results using laminarin as substrate [Parrish and Reese (1963) Carbohydr. Res. 3, 424-429; Nelson (1970) J. Biol. Chem. 245, 869-872]. PMID- 8343140 TI - The specification of sensory neuron identity in Drosophila. AB - Different types of sense organs are present on the larva of Drosophila. Several genes that specify the type of sense organ that will form at a particular position have been recently identified. Here we review the functional and molecular analyses of these genes, and summarize the evidence which supports a role in the choice of which type of organ will be formed. Most or all of these genes are required for the appropriate specification of adult as well as larval sense organs, suggesting that the larval and adult systems share many gene requirements. Interestingly, the specifying genes identified so far in the peripheral nervous system are also expressed in subsets of cells in the central nervous system, where they might have similar roles. PMID- 8343139 TI - Mg2+ affects the binding of ADP but not ATP to 3-phosphoglycerate kinase. Correlation between equilibrium dialysis binding and enzyme kinetic data. AB - The role of Mg2+ in the binding of ADP and ATP to pig muscle and yeast 3 phosphoglycerate kinases has been studied by equilibrium dialysis. Whereas the Kd of ATP binding varies between 0.17 and 0.23 mM (S.E.M. 0.03 mM) for both enzymes, independently of the presence of Mg2+, the Kd values for ADP and MgADP binding are in the range 0.18-0.27 mM (S.E.M. 0.04 mM) and 0.05-0.06 mM (S.E.M. 0.01 mM) respectively. Thus Mg2+ exclusively tightens the interaction of ADP, but not of ATP, with the protein molecule. Although the equilibrium dialysis data are consistent with a model possessing a single site for nucleotides, the existence of a much weaker secondary site (with a Kd value at least two orders of magnitude larger) cannot be excluded. The binding of AMP and adenosine to pig muscle 3 phosphoglycerate kinase is weaker than binding of MgATP; the respective Kd values are 0.36 +/- 0.05 mM and 0.65 +/- 0.05 mM. Thus, in addition to the interaction of the alpha-phosphate that is detectable by crystallography [Banks, Blake, Evans, Haser, Rice, Hardy, Merrett and Phillips (1979) Nature (London) 279, 773 777], the beta- and/or gamma-phosphate(s) of MgATP may also interact with the enzyme molecule. The fact that MgADP binds more tightly than ADP is consistent with its stronger inhibition of the reaction catalysed by the enzyme between 3 phosphoglycerate and MgATP. MgADP is a product of this reaction, and inhibits it competitively with both substrates; as an inhibitor its KI is comparable with the Kd found in binding studies. At the same time, the Km value for MgADP in the reverse reaction (0.18 +/- 0.05 mM; mean +/- S.E.M.) is higher than these constants; this may be due either to a different kinetic mechanism in this direction of the enzymic reaction, or to different binding modes of MgADP as inhibitor and as substrate. The reason why inhibition by MgADP is competitive with 3-phosphoglycerate may be that its binding prevents the specific change in conformation that the enzyme undergoes [Harlos, Vas and Blake (1992) Proteins 12, 133-144] when it binds 3-phosphoglycerate. PMID- 8343141 TI - RNA as a catalyst: natural and designed ribozymes. AB - RNA can catalyse chemical reactions through its ability to fold into complex three-dimensional structures and to specifically bind small molecules and divalent metal ions. The 2'-hydroxyl groups of the ribose moieties contribute to this exceptional reactivity of RNA, compared to DNA. RNA is not only able to catalyse phosphate ester transfer reactions in ribonucleic acids, but can also show amino-acyl esterase activity, and is probably able to promote peptide bond formation. Bearing its potential for functioning both as a genome and as a gene product, RNA is suitable for in vitro evolution experiments enabling the selection of molecules with new properties. The growing repertoire of RNA catalysed reactions will establish RNA as a primordial molecule in the evolution of life. PMID- 8343142 TI - Protein targeting to dense-core secretory granules. AB - Regulated secretory proteins are stored within specialized vesicles known as secretory granules. It is not known how proteins are sorted into these organelles. Regulated proteins may possess targeting signals which interact with specific sorting receptors in the lumen of the trans-Golgi network (TGN) prior to their aggregation to form the characteristic dense-core of the granule. Alternatively, sorting may occur as the result of specific aggregation of regulated proteins in the TGN. Aggregates may be directed to secretory granules by interaction of a targeting signal on the surface with a sorting receptor. Novel targeting signals which confer on regulated proteins a tendency to aggregate under certain conditions, and in so doing cause them to be incorporated into secretory granules, have been implicated. Specific targeting signals may also play a role in directing membrane proteins to secretory granules. PMID- 8343143 TI - DNA damage and cell cycle regulation of ribonucleotide reductase. AB - Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage. PMID- 8343144 TI - Mammalian cells can trans-splice. But do they? PMID- 8343145 TI - Chromosome bands--flavours to savour. AB - The mammalian chromosome is longitudinally heterogeneous in structure and function and this is the basis for the specific banding patterns produced by various chromosome staining techniques. The two most frequently used techniques are G, or Giemsa banding and R, or reverse banding. Each type of stained band is characterised by variations in gene density, time of replication, base composition, density of repeat sequences, and chromatin packaging. It is increasingly apparent that R and G bands, which are complementary to each other, represent separate compartments of the euchromatic human genome, with R bands containing the vast majority of genes. R bands are also more GC-rich, contain a higher density of Alu repeats, and replicate earlier in S phase, than G bands. These properties may be interdependent and may have coevolved. PMID- 8343146 TI - The inhibition of HIV-1 protease by interface peptides. AB - Previous studies have shown that some peptides derived from one of the terminal amino acid segments of the homodimeric HIV-1 protease show moderate inhibition of this enzyme probably by interfering with the "interface" structure formed by the four terminal segments of the dimer. Different peptides, with improved inhibitory potency, were devised by computer modelling, synthesized, and tested. Ac-TVSFNF, the short peptide with the best inhibition so far (IC50 = 80 microM) is identical with the C-terminal part of the gag-pol frame shift protein p6*. This suggests a regulatory function of p6* as a dimerization inhibitor of HIV protease in the virion. Peptides derived from the active site sequence of PR are inactive. The two terminal hexapeptides of reverse transcriptase are also inactive in the HIV-1 PR activity assay. PMID- 8343147 TI - Increase in albumin mRNA by repeated intrahepatic transplantation of F344 rat hepatocytes into the liver of congenic analbuminemic rats. AB - Hepatocytes of F344 rat were transplanted into the liver of congenic analbuminemic rats by infusion into the mesenteric vein from once to four times at one-week intervals. The transplantability was confirmed by the increase in the number of albumin-positive cells and appearance of normal albumin mRNA within the recipient liver, and the elevated serum albumin level. When the normal albumin mRNA was quantitated by reverse transcriptase polymerase chain reaction (RT-PCR) using the abnormally spliced albumin mRNA of analbuminemic rats as an internal standard, the increase in normal mRNA was in good agreement with the serum albumin level and the number of albumin positive hepatocytes within the liver. These three markers proportionally increased with the number of infusion times. Our results demonstrate that the number of intrahepatically transplanted hepatocytes is able to be increased by repeated infusion. PMID- 8343148 TI - Allyl compounds selectively killed human immunodeficiency virus (type 1)-infected cells. AB - Various allyl compounds were tested as anti-HIV reagents. Of all the allyl compounds tested, allyl disulfide (CH2 = CH-CH2-S-S-CH2-CH = CH2), allyl alcohol (CH2 = CH-CH2-OH), and its ester strongly depressed cell proliferation of HIV-1 infected cells. KC50 (50% killing concentration) of the allyl disulfide and the allyl alcohol were 34 microM and 10 microM, respectively. The allyl alcohol, in particular, completely inhibited cell growth of HIV-1-infected cells by a single injection at a concentration of 40 microM, ultimately killing the viable CEM/LAV 1 cells within 96 hr cultivation. No effect of the allyl alcohol and its esters on cell proliferation of CEM cells, which are a HIV-1 noninfected human T-cell cell line, was observed at the concentration range of 20 to 200 microM under the same experimental conditions. The results suggest that the effect of the allyl alcohol and its esters resulted in remarkable promotion of the cytopathic effect induced by HIV-1 virus. PMID- 8343149 TI - Molecular identification of onchocerciasis vector sibling species in black flies (Diptera: Simuliidae). AB - A number of sibling species in the Simulium damnosum species complex transmit River Blindness (onchocerciasis) in tropical Africa. Black fly sibling species can be reliably recognized only through analysis of the larval polytene chromosomes. The routine, unambiguous assignment of the potentially disease transmitting adult females to a particular species is virtually impossible. Two molecular assays to identify the sibling species of biting female flies are presented. The first relies on PCR-mediated amplification of internal transcribed spacers of the nuclear rDNA loci while the second involves immunoblotting of silk proteins which are expressed in both larvae and adult females. Both assays yield sibling-specific size markers that can be used to identify the sibling species of biting adult females. To illustrate the use of these assays, a molecular characterization is given for two S. damnosum siblings (squamosum, sirbanum) collected from cytologically verified populations, and a partial characterization of a third sibling (damnosum s. str.) found as a contaminant in these samples. PMID- 8343150 TI - Modulation of rat liver protein kinase C during "in vivo" CC14-induced oxidative stress. AB - Rat intoxication with a single dose of the hepatotoxin carbon tetrachloride induces a significant modification of liver protein kinase C total activity which depends on the degree of the intrahepatocyte oxidative unbalance provoked by various concentrations of the haloalkane. Low carbon tetrachloride amounts stimulate total protein kinase C activity, while one order of magnitude higher amounts exert strong enzyme inhibition. The latter effect is due to an early inactivation followed with progress of time by a proteolytic degradation of the enzyme. A pathological recruitment of the calcium-dependent protein kinase C regulatory enzymes calpain and calpastatin appears responsible for protein kinase C loss. The prolonged excess of cytosolic calcium which characterizes the single high dose carbon tetrachloride poisoning also leads to inactivation of calpain II and calpastatin in a time-dependent manner. PMID- 8343151 TI - Hyperosmotic stress induces immediate-early gene expression in ventricular adult cardiomyocytes. AB - Mammalian cells possessing osmosensors have long been described in brain and kidney. The genetic basis of the response to hyperosmotic stress has been well characterized in prokaryotes. In contrast, the genetic response of eukaryotic cells is poorly understood. Therefore we investigated the effect of hypertonic NaCl and sucrose solutions on the transcriptional activation of the immediate early genes (IEGs) egr-1 and c-fos in isolated ventricular adult rat cardiomyocytes. We observed that even small increases in osmolarity to 315 +/- 5 mosmol/l and 370 +/- 8 mosmol/l by hypertonic NaCl solution resulted in dose dependent induction of egr-1 (4-and 5-fold) and c-fos (3-and 4-fold), respectively. Hypertonic sucrose solution had the same effect on egr-1 and c-fos mRNA levels while increased sucrose concentration under isotonic conditions had no effect. Cardiomyocytes exposed to hypertonic media did not significantly shrink as shown by a cell length measurement. We conclude that isolated adult cardiomyocytes possess an osmoreceptor mechanism which is able to sense even slight changes in osmolarity and to translate these into a transcriptional response of the myocardial IEG program. PMID- 8343152 TI - S1 nuclease-sensitive sites in the bithoraxoid region of the Drosophila Ultrabithorax gene. AB - The Ultrabithorax gene is required to specify the third thoracic and first abdominal segments of Drosophila melanogaster. Mutations in the bithoraxoid region, a 40 kb DNA stretch upstream of the Ultrabithorax promoter, affect cis regulatory elements of the Ultrabithorax gene. We now have identified specific sites in the bithoraxoid region that exhibit S1 nuclease sensitivity in vitro. These sites are not scattered along the DNA but are grouped instead in specific domains. Some of these S1-sensitive sites correlate with known breakpoint or insertional mutations. Others correspond to putative binding sites for transcription factors. The results suggest that unusual secondary structure might be important in chromosomal translocation within regulatory sequences of the Ultrabithorax product or its transcriptional regulation. PMID- 8343153 TI - Chromosomal localization of angiotensin II type 1 receptor isoforms in the rat. AB - The cDNA sequences of two different isoforms of the rat angiotensin II type 1 receptors, AT1A and AT1B, have been reported. A single set of polymerase chain reaction primers was used to amplify sequence from both AT1A and AT1B from rat genomic DNA. Genomic DNA from a panel of rat x mouse somatic hybrid cell lines which had been characterized as to the rat chromosomal content was then amplified with these primers. The amplified products from rat AT1A and AT1B were distinguished from each other and those of the mouse by the use of differential restriction patterns. Using this method, AT1A was localized to rat chromosome 17 and AT1B to rat chromosome 2. PMID- 8343154 TI - trk immunoreactivity at neuronal dendrite and cell body. AB - Neurotrophins homologous to the nerve growth factor (NGF) bind the neurotrophic receptors of the trk gene family. Since the target tissues release these neurotrophic factors to the neuron, it has been believed that their trophic effects are mediated by the retrograde axonal transport. However it remains an open question whether the neurotrophins act through the autocrine or the paracrine mechanisms, since the protein-level expression of trk has not been studied so far. We have made polyclonal antibodies against the recombinant proteins of chicken trkC and rat trkB. These antibodies showed immunoreactivity at the dendrite and the cell body of neuron. This subcellular localization strongly suggests the autocrine or the paracrine mechanism of the neurotrophic factors. At the same time, our data provide basic knowledge to decide where to deliver these neurotrophic factors in the therapy of neurodegenerative diseases. PMID- 8343155 TI - Isolation and identification of an endogenous inhibitor of enkephalin-degrading enzymes from bovine spinal cord. AB - We isolated a potent inhibitor of enkephalin-degrading enzymes from bovine spinal cord and determined its amino-acid sequence and inhibitory activity toward enkephalin-degrading enzymes. This new substance, designated spinorphin, is composed of a heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr). The inhibitory activity (IC50) of this new substance toward enkephalin-degrading enzymes, purified from monkey brain, was found to be 3.3 micrograms/ml against aminopeptidase, 1.4 micrograms/ml against dipeptidyl aminopeptidase, 2.4 micrograms/ml against angiotensin-converting enzyme, and 10 micrograms/ml against enkephalinase. This new substance did not show inhibitory activity toward enkephalin degrading enzymes purified from kidney and blood. Above results suggest that this substance is a new neuromodulator in the spinal cord. PMID- 8343156 TI - Caffeine inhibits Ca(2+)-mediated potentiation of inositol 1,4,5-trisphosphate induced Ca2+ release in permeabilized vascular smooth muscle cells. AB - We studied the effects of caffeine on inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release in saponin-permeabilized smooth muscle cells. The Ca2+ concentration in the vicinity of the Ca2+ store was strongly buffered to exclude the secondary effect of Ca2+ on the Ca2+ release. 2 mM caffeine shifted the IP3 concentration Ca2+ release relation at 100 nM Ca2+ to the higher IP3 concentration without decreasing the steepness of the relation. The ascending limb of the biphasic Ca2+ dependence of IP3-induced Ca2+ release was shifted to the higher Ca2+ concentration by 2 mM caffeine. However, caffeine showed little inhibitory effect in the absence of Ca2+. These results indicate that caffeine inhibits IP3-induced Ca2+ release only when the Ca2+ release is potentiated by Ca2+. PMID- 8343157 TI - Cloning of gene responsible for tributyltin chloride (TBTC1) resistance in TBTC1 resistant marine bacterium, Alteromonas sp. M-1. AB - A genetic library of tributyltin chloride (TBTC1)-resistant marine bacterium, Alteromonas sp. M-1, was constructed using plasmid vector pUC 19. Three positive clones were obtained from E. coli JM 109 transformed with the plasmids by the method of replica plating to LB medium containing 1 mM TBTC1. These clones could grow in LB liquid medium containing 100 microM TBTC1. Plasmids harbouring genes of Alteromonas sp. M-1 were designated pTBT1, pTBT2 and pTBT3 which contain 1.8 kb Hind III-fragment, 4.8 kb Pst I-fragment and 7.8 kb Pst I-fragment, respectively. Nucleotide sequence of the shortest fragment, 1.8 kb Hind III fragment was determined, revealing an open reading frame (ORF) was contained in the fragment. The ORF was 324 bp (108 amino acids). The 48.5% of the amino acids encoded was hydrophobic, suggesting that the product relating to TBTC1 resistance might be membrane related protein. Homology search in amino acids alignment indicated that the product has homology with transport proteins. PMID- 8343158 TI - Vascular myocyte-derived nitric oxide is an autocrine that limits vasoconstriction. AB - Vascular myocytes and endothelial cells possess the enzymatic machinery to generate nitric oxide from L-arginine. This study tests the hypothesis that myocyte-derived nitric oxide has an autocrine function to inhibit contraction. Rat aortic rings were placed in muscle baths for isometric force measurement. Denuded and intact rings contracted to N omega nitro-L-arginine; L-arginine reversed these contractions. Compared to intact rings, contractile sensitivity to phenylephrine was increased in denuded rings; N omega nitro-L-arginine caused a further enhancement of phenylephrine sensitivity. Acetylcholine contracted denuded rings but not intact rings; these contractions were also potentiated by N omega nitro-L-arginine. In intact rings contracted with phenylephrine, acetylcholine caused relaxation that was inhibited by N omega nitro-L-arginine. Denuded rings did not relax to acetylcholine. In summary, contractile responses of rat aortae to interventions that alter nitric oxide production are the composite of enzymatic activity in both the endothelial cells and myocytes. Thus, myocyte-derived nitric oxide modulates vascular tone. PMID- 8343159 TI - Lipoprotein lipase facilitates very low density lipoprotein binding to the subendothelial cell matrix. AB - The effect of bovine lipoprotein lipase (LPL) on very low density lipoprotein (VLDL) binding to subendothelial matrix was studied. Without LPL, VLDL bound poorly to the matrix. However, decreasing NaCl or elevating Ca++ concentration increased matrix VLDL binding. With LPL, VLDL binding was markedly increased. Since LPL is a normal constituent of the artery wall and is elevated in atherosclerotic lesions, we postulate two potential mechanisms for the involvement of VLDL and LPL in atherogenesis. First, VLDL acquisition is attenuated by the increased matrix LPL content in the developing atheroma. Secondly, elevated plasma levels of VLDL (and VLDL remnants) such as in Type II or III dyslipidemia could enhance such interactions. These events likely accelerate the rate of atherosclerosis lesion development. PMID- 8343160 TI - A characterization of the H3 and H4 histone genes from the ascidian Styela plicata. AB - Information about histone sequences and histone gene organization from invertebrate chordates is completely lacking. A genomic clone containing linked H3 and H4 histone genes from the urochordate Styela plicata was analyzed. The nucleotide sequence indicates that the two genes are transcribed in opposite directions and have structural similarities to cell cycle-dependent histones. Unique amino acid replacements occur in H3 at positions 88 (serine) and 98 (arginine). In H4, the methionine at position 84 is replaced by a leucine, a replacement found only in fungi. Codon usage patterns are nonrandom and resemble invertebrate patterns. The H3 and H4 genes are polymorphic and are represented five times per haploid genome. PMID- 8343161 TI - Biosynthesis and oligosaccharide processing of human Tamm-Horsfall glycoprotein permanently expressed in HeLa cells. AB - Human Tamm-Horsfall glycoprotein (T-H) is produced by renal cells of ascending limb of loop of Henle and is largely excreted in urine. N-linked glycans account for close to 30% of the weight of T-H. We studied the biosynthesis of recombinant T-H permanently expressed in HeLa cells. The conversion from the precursor (84 kDa) to the mature form (97 kDa) mainly depends on the processing of glycans from the high-mannose to polyantennary type. The conversion from precursor to mature form is very slow and the glycan structure of precursor appears to be that of a glycoprotein not yet processed by Golgi alpha 1,2 mannosidase. Since T-H has a very high number of disulfide bridges (more than 50 cysteine residues/mol) one may infer that the rate limiting step for the precursor export out of ER is the formation of a correct set of disulfide bonds. Mature T-H isolated from HeLa cells retained one N-linked chain with the high-mannose structure similarly to urinary T-H. This result indicates that the occurrence of one unprocessed high mannose chain in mature T-H is host-cell independent and very likely related to the T-H primary structure. PMID- 8343162 TI - A missense mutation of cardiac beta-myosin heavy chain gene linked to familial hypertrophic cardiomyopathy in affected Japanese families. AB - A novel missense mutation of the cardiac beta-myosin heavy chain gene was detected in five unrelated Japanese patients and their affected family members with hypertrophic cardiomyopathy (HCM) by using the polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis. Sequencing analysis revealed an A to G transition at codon 778 leading to replacement of the Asp residue, which is adjacent to the interaction sites of myosin heavy chain (MHC) with actin and is a conserved amino acid residue in various MHC across species, to the Gly residue. Linkage study of the mutation and two dinucleotides repeat markers of the cardiac beta-MHC gene in three affected families showed that the mutation was on the same haplotype of the cardiac beta-MHC gene and linked to HCM. These observations strongly suggest that the 778Asp to Gly mutation is the cause of HCM in these affected individuals. PMID- 8343163 TI - Expression of vascular endothelial growth factor by cultured endothelial cells from brain microvessels. AB - Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells that may be involved in tumor angiogenesis. Cultured capillary endothelial cells from rat brain (BCEC) express transcripts for VEGF as assayed by Northern blots and polymerase chain reaction analysis. The three forms of VEGF (VEGF120, VEGF164 and VEGF188) are produced, VEGF188 being detected in lower amounts. The sequence of rat VEGF188 was determined. Rat and human exons 6 differ at only one position (human Tyr134-->rat Phe133). Transcripts for VEGF were observed in different clones of rat BCEC, in bovine BCEC but not in bovine aortic endothelial cells. PMID- 8343164 TI - Conformational states of human placental glutathione transferase as probed by limited proteolysis. AB - Limited proteolysis experiments have been carried out on human placental glutathione transferase in its different forms. The reduced enzyme, as well as the oxidized form and that inactivated with cystamine were all sensitive to 10% (w/w) trypsin, under nondenaturing conditions. The proteolytic cleavage was accompanied by a concomitant loss of enzymatic activity. On the contrary, the presence of glutathione or glutathione conjugates strongly protected the reduced enzyme against inactivation and from the proteolytic attack. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and peptide sequence analysis showed that only the peptide bond between Lys 44 and Ala 45 was cleaved. Since Lys 44 has been demonstrated to be involved in the glutathione binding, it is suggested that the region surrounding this amino acid residue (alpha B helix) could be more exposed to the solvent, in the absence of glutathione. Crystallographic data also indicated that this region is flexible, supporting the idea that it may be involved in the observed conformational change upon glutathione binding. PMID- 8343165 TI - Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor. AB - The cholecystokinin (CCK) family of peptides and receptors are present throughout the brain and gastrointestinal tract and can be pharmacologically subdivided into two subtypes: CCKA and CCKB. Little is known about the localization, pharmacology and function of CCKA receptors (CCKAR) in humans. We used the rat CCKAR cDNA to isolate the human CCK receptor cDNA homologue from human gallbladder which encodes a unique 428 amino acid protein having > 90% homology to the rat and guinea pig CCKAR. Expression of the recombinant CCKAR in COS-7 cells displayed a pharmacological profile characteristic of a CCKAR subtype and mediated agonist stimulated increase in total inositol phosphates. Northern hybridization identified a transcript measuring 6 Kb. The human CCKAR gene maps to chromosome 4. These results describe for the first time the molecular cloning, expression and chromosomal localization of the human CCKA receptor. PMID- 8343166 TI - Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats. AB - Rat migration inhibitory factor-related protein 8 (MRP8) and MRP14 were identified during screening of a subtracted cDNA library generated to identify differences in gene expression between LEW/N and F344/N rats. The predicted amino acid sequence of rat MRP8 and MRP14 is 60-80% identical with that from human and mouse. Expression of these genes correlated with chronic inflammation in LEW/N rats, but were absent in F344/N rats which do not develop arthritis in response to streptococcal cell wall peptidoglycan-polysaccharide complexes (SCW). These differences suggest a role for MRP8 and MRP14 in susceptibility to SCW-induced chronic disease. PMID- 8343167 TI - Spontaneous nucleosomal DNA fragmentation in murine leukemic L1210 cells. AB - Spontaneous nucleosomal DNA fragmentation (SNDF), characteristic of apoptotic cell death was observed in a murine leukemic cell line grown to high density. This effect was eliminated by permitting free diffusional exchange with a large amount of complete medium. Cells seeded at low density did not show SNDF in a conditioned medium that had been used to culture cells with severe SNDF. Cells seeded at high density in the same conditioned medium showed pronounced SNDF, but addition of 10% fetal bovine serum to such a medium significantly reduced SNDF. These observations indicate that neither physical contact among cells in high density culture per se nor secretion of a death factor by the high density culture could account for the induction of SNDF. The results support a model in which the gradual depletion of a serum factor(s) leads to the activation of a cell death program that is manifested as SNDF. PMID- 8343168 TI - Exogenous phospholipase C specifically inhibits apoE expression in mouse peritoneal macrophages. AB - Treatment of cholesterol-loaded mouse peritoneal macrophages with exogenous phospholipase C results in a specific and dose-dependent inhibition of apoE secretion. The inhibition of apoE secretion is secondary to the rapid and specific inhibition of its synthesis. The profound changes in rates of apoE synthesis are not accompanied by changes in the levels of apoE mRNA, an observation strongly suggestive of translational regulation of expression. The changes in apoE expression coincide with, or are preceded by a three-fold increase in membrane-bound protein kinase C activity, pointing out the potential importance of this signal transduction pathway in regulating apoE expression at a posttranscriptional locus. PMID- 8343169 TI - Retinoblastoma gene product-associated proteins in human colon cancer cell lines. AB - The expression of cellular proteins that associate with the human retinoblastoma (RB1) gene protein was examined in three colorectal carcinoma cell lines (SW480, SW403, DiFi) by immunoprecipitation analysis, using the mouse monoclonal antibody (RB-MAb-1) directed against the RB1 gene product (RB). The potential of RB-MAb-1 to detect RB-associated proteins by immunoprecipitation analysis was confirmed using three control cell lines (WI-38, J82, T24) known to express RB and/or RB associated proteins. In all colon cancer cell lines tested, multiple RB associated protein (RAP) bands were found with molecular weights of 30-50 kDa. Because involvement of the RB1 gene in colorectal tumorigenesis appears to differ from its role in other cancer types (wherein RB1 is lost or inactivated), it will be important to characterize the role of RAPs in RB growth regulatory mechanisms of colonic epithelial cells. PMID- 8343170 TI - Tumor cell retention of antibody Fab fragments is enhanced by an attached HIV TAT protein-derived peptide. AB - Two peptide analogs of the 37-62 sequence region of the HIV TAT protein bind tightly to the surface of A431 breast carcinoma cells. After conjugation to either of two poorly internalized anti-tumor antibody Fab fragments, the analogs enhanced the in vitro cell surface retention and internalization of the Fab fragments to the level of the whole antibodies. This was at the expense of some binding specificity in the case of 1.6 peptides/NRLU-10 Fab, but not in the case of 1.1 peptides/Fab. Enhanced retention may occur by enhanced bivalent binding of the Fab fragments. The internalized fraction of free peptide, but not of the Fab conjugates, is enhanced by chloroquine. The conjugates which were less specific for tumor cell binding may be useful for enhanced retention/internalization of specifically acting agents, for use at specific sites of injection, or against pre-separated target cell populations, while the more specific conjugate may be of interest for further development. PMID- 8343171 TI - Double-stranded RNA triggers generalized translational arrest in Xenopus oocytes. AB - Controls of gene expression which act at the translational level can be rapidly activated and readily reversed. The impact of double-stranded RNA on translational control is of significant interest as a number of studies point to its ability to directly activate generalized translational arrest. This activity is observed in in vitro systems stimulated by native double-stranded RNAs or synthetic homopolymers and is inferred in virally infected cells in tissue culture. Significantly, however, this activity has never been studied in an intact cell system using RNAs of known secondary structure. In this study we arrest total cellular translation in intact Xenopus oocytes by micro-injecting them with alpha-globin-derivative mRNAs containing defined double-stranded segments. The ability of these mRNAs to directly activate translational arrest in oocytes substantiates the potential role for this activity in vivo and establishes a well-characterized whole cell system for its further study. PMID- 8343172 TI - Newly established murine pituitary folliculo-stellate-like cell line (TtT/GF) secretes potent pituitary glandular cell survival factors, one of which corresponds to metalloproteinase inhibitor. AB - A mouse folliculo-stellate cell (FS cell) line, TtT/GF, was found to secrete a potent survival factor influencing a somatotropic cell line (MtT/S) in serum-free medium. A three-step chromatography purification procedure using heparin-affinity chromatography, anion-exchange chromatography and gel-filtration chromatography revealed that the factor was a 27 kDa protein. Amino-terminal sequence analysis showed that the N-terminal 20 amino acids of the 27 kDa protein corresponded to those of human tissue inhibitor of metalloproteinase-II (TIMP-II). These results indicate that FS cells secrete TIMP-II, which probably protects the composition of the extracellular matrix and acts as a cell survival factor for endocrine cells in the anterior pituitary gland. PMID- 8343173 TI - ADP-ribosylation of neurofilaments by a cytoplasmic ADP-ribose transferase associated with free mRNP. AB - ADP-ribosylation of neurofilaments by an ADP-ribose transferase isolated from cytoplasmic ribonucleoprotein particles is demonstrated. The 150 kDa neurofilament subunit appears to be the main ADP-ribose acceptor with the transfer of ADP-ribose dimers or monomers. A binding of about 1 mole ADP-ribose per 8 moles of neurofilament subunits has been recorded. An interaction between neurofilaments' ADP-ribosylation and their phosphorylation state is demonstrated. PMID- 8343175 TI - Direct electrochemical measurement of nitric oxide released from human platelets. AB - A porphyrinic microsensor has been used to investigate the release of nitric oxide (NO) from human platelets in whole blood and in washed platelet suspensions. Basal release of NO was not detectable. Aggregation of platelets by collagen (1-15 micrograms/ml) but not by thrombin (0.1 U/ml) resulted in a concentration-dependent release of NO. This release was prolonged and potentiated by L-arginine (100-1000 microM) and inhibited by NG-monomethyl-L-arginine (300 microM). These data support our previous findings that human platelets generate NO during aggregation. PMID- 8343174 TI - Analysis of cleavage-site patterns in protein precursor sequences with a perceptron-type neural network. AB - A method for feature extraction from protein sequences has been developed which is based on an artificial neural filter system. Amino acid sequences are analyzed with regard to physicochemical residue properties. This alternative representation of a sequence allows an interpretation of the networks' weight values in a comprehensive and biochemically meaningful way by displaying the optimized network weights in Hinton diagrams. Signal peptidase cleavage sites of E.coli periplasmic proteins, human mitochondrial precursors and chloroplast precursors from spinach have been investigated. The network for E.coli periplasmic protein precursors classified both training and test data with 100% accuracy. The interpretation of its network weights clearly confirms the "-3,-1 rule" and the existence of a hydrophobic core region starting at position -6. Further striking features and dominant positions can be found for all three types of cleavage sites. PMID- 8343176 TI - Deoxyribocytidine is salvaged not only into DNA but also into phospholipid precursors. IV. Exogenous deoxyribocytidine can be used with the same efficacy as (ribo)cytidine for lipid activation. AB - Utilisation of exogenous (ribo)cytidine (3H-CR) and deoxyribocytidine (3H-CdR) for DNA/RNA synthesis and for activation of phospholipid intermediates was compared in human tonsillar lymphocytes. Incorporation of 3H-CdR into dCDP choline and into dCDP-DAG was similar or even higher than labelling of CDP choline and CDP-DAG from 3H-CR. No interconversion was found between CDP-DAG and dCDP-DAG, as shown by TLC separation of the ribo- and deoxyribocytidine derivatives. Moreover, a strict separation was found between the salvage pathways of deoxyribocytidine and (ribo)cytidine, as 4000-fold excess of non labelled (ribo)cytidine did not show any specific effect on 3H-dCDP-DAG labelling from exogenous 3H-CdR. PMID- 8343177 TI - Scanning tunnelling microscopy of collagen I reveals filament bundles to be arranged in a left-handed helix. AB - Collagen I is the most abundant protein found in the body. Its quaternary structure has been extensively characterised and consists of filaments arranged into bundles. In this study we used scanning tunnelling microscopy to image the collagen I filaments and fibrils directly. The images suggested that filaments are arranged into a left-handed helical structure with a periodicity of about 10nm. Such a structure potentially adds increased tensile strength to the collagen fibrils. PMID- 8343178 TI - Implication of cysteine residues in the activity of single-chain urokinase plasminogen activator. AB - Single-chain urokinase-plasminogen activator contains 24 cysteine residues involved in 12 disulfide bonds and distributed all along the three domains of the protein. In order to investigate the role of these disulfide bridges in the catalytic activities of scu-PA, we used site-specific mutagenesis to construct 10 mutants in which some cysteine residues were changed to serine residues. Each mutated DNA fragment was cloned into a procaryotic expression vector and the protein expressed in E. coli. Mutant proteins of the expected size were produced and analyzed for amidolytic and fibrinolytic activities. From this, it is shown that: i) the disulfide bonds in the epidermal growth factor (EGF)-like and in the kringle domains are not necessary. Moreover, disulfide bond deletion in the kringle domain improves those catalytic activities; ii) on the contrary, the disulfide bridges in the catalytic domain are essential for maintaining both activities. PMID- 8343179 TI - Geriatric rheumatology. PMID- 8343180 TI - Nitric oxide and arthritis. PMID- 8343182 TI - Antineutrophil cytoplasmic antibodies in rheumatoid arthritis. Characterization and clinical correlations. AB - OBJECTIVE: To study the prevalence, interrelationships, and target antigens of antineutrophil cytoplasmic antibodies (ANCA) in rheumatoid arthritis (RA) and to relate their presence to disease duration and to the occurrence of extraarticular manifestations, including vasculitis. METHODS: Sera from 94 patients with RA (31 with recent-onset disease, 35 with longstanding disease but without extraarticular manifestations, and 28 with extraarticular disease) were studied for the presence of ANCA by indirect immunofluorescence. All sera were tested by enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to proteinase 3, myeloperoxidase (MPO), elastase, lactoferrin (LF), and cathepsin G (CG), and by Western blotting for antibodies to neutrophil proteins. RESULTS: Seventy percent of the 94 sera showed staining of the nuclei of ethanol-fixed neutrophils; 32% of the 94 were proven to have ANCA, as manifested by their cytoplasmic staining pattern on paraformaldehyde-fixed neutrophils. In the ELISA, 19 sera reacted with LF, 1 with MPO, and 1 with CG. By Western blotting, 21 sera reacted with LF, and 15 reacted with previously unknown polypeptides (7 sera with a 67/66-kd doublet and 8 with a 63/54-kd doublet). Neither of these antibodies was associated with a particular subset of the disease, but the prevalence of the antibodies tended to increase among patients with longstanding disease. CONCLUSION: ANCA in RA patients are directed toward diverse cytoplasmic antigens of the neutrophil, in particular, LF and other, not yet fully characterized polypeptides. The antibodies are not a marker for a disease subset, but are probably a corollary of chronic inflammation. PMID- 8343181 TI - Rheumatoid arthritis and mortality. A longitudinal study in Pima Indians. AB - OBJECTIVE: To determine the effect of rheumatoid arthritis (RA) on mortality rates. METHODS: Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989. RESULTS: Among 2,979 study subjects aged > or = 25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age- and sex-adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01-1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10-year increase in age, 95% CI 1.22-1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44 3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02-3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10-3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10-2.84) and from liver cirrhosis or other alcohol-related disease (mortality rate ratio 2.52, 95% CI 1.06-6.01) was increased in persons with RA. CONCLUSION: The results of this population-based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic-based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death. PMID- 8343183 TI - The repertoire of rheumatoid factor-producing B cells in normal subjects and patients with rheumatoid arthritis. AB - OBJECTIVE: To compare the B cell repertoire of normal individuals and patients with rheumatoid arthritis (RA) and, specifically, to identify precursor B cells with the potential to secrete rheumatoid factor (RF) and to understand the T helper cell requirements for the production of this autoantibody. METHODS: Frequencies of precursors of IgM-, IgG-, and RF-producing B cells were measured in a limiting-dilution system. Two distinct sources of T cell help were compared. T cell help was provided by anti-CD3-activated CD4+ human T cell clones, or T cell-B cell interaction was facilitated by the bacterial super-antigen staphylococcal enterotoxin D (SED). RESULTS: A subset of 2-14% of peripheral blood B cells secreted IgM and IgG in SED-driven cultures. The SED-responsive B cell subpopulation was present at 10 times higher frequency in normal donors compared with RA patients. However, the repertoires were very similar, particularly for RF+ precursors, which represented approximately one-third of all SED-responsive B cells. In normal individuals, most of these RF+ precursor B cells did not respond to anti-CD3-activated T helper cells, with only a very small fraction of B cells activated by anti-CD3-driven helper cells maturing into RF-secreting B cells (from 1 of 182 to 1 of 889 IgM-producing B cells). This subset was expanded approximately 50-fold in RA patients. CONCLUSION: Normal subjects and RA patients share a pool of B cells which secrete RF when activated in the presence of SED and T helper cells. These B cells are frequent and obviously anergic in normal individuals. The B cell subset with the potential to produce RF when help is provided in noncognate T-B interaction (anti-CD3-driven T cells) is considerably expanded in RA patients, probably reflecting an increased responsiveness of such B cells to helper signals. PMID- 8343184 TI - Detection of herpesviruses by polymerase chain reaction in lymphocytes from patients with rheumatoid arthritis. AB - OBJECTIVE: To investigate the occurrence of herpesviruses, including Epstein-Barr virus (EBV), herpes simplex viruses types 1 and 2 (HSV-1; HSV-2), and human herpesvirus 6 (HHV-6), in lymphocytes from patients with rheumatoid arthritis (RA) of less than 1 year's duration. METHODS: The polymerase chain reaction was applied to cells isolated from synovial fluid and peripheral blood. Indirect immunofluorescence and enzyme immunoassay techniques were used to detect antibodies against EBV and HSV, respectively. RESULTS: EBV DNA was present in synovial fluid lymphocytes from 19% (7 of 37) of the RA patients and 33% (5 of 15) of the patients with reactive arthritis (ReA). Peripheral blood lymphocytes harbored EBV DNA in 39% of the RA patients, 39% of the ReA patients, 27% of the patients with other arthropathies, and in 31% of the healthy control subjects. HSV-1, HSV-2, and HHV-6 viral DNA was not detected in cells from the synovial fluid or peripheral blood. CONCLUSION: Our findings do not support the participation of EBV, HSV-1, HSV-2, or HHV-6 in the pathogenesis of RA. A role for the highly prevalent EBV cannot be excluded, however, since potential contributions may become manifest only when other necessary factors are involved. RA pathogenesis caused by an overproduction of the EBV virus is nevertheless highly unlikely. PMID- 8343185 TI - Presence of estrogen-binding sites on macrophage-like synoviocytes and CD8+, CD29+, CD45RO+ T lymphocytes in normal and rheumatoid synovium. AB - OBJECTIVE: To study the presence of estrogen-binding sites (EBS) in the synovial tissues of male and female patients with rheumatoid arthritis (RA) and in age- and sex-matched healthy controls. METHODS: Both type 1 (high affinity, low binding capacity) and type 2 (reduced affinity, higher binding capacity) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue samples by a dextran-coated charcoal method. To determine what type of synovial cell was positive for EBS, cryosections of synovial tissues were immunostained with a specific monoclonal anti-estrogen receptor antibody (anti-ER MAb) using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens (Ber-MAC3, MAC387, CD68) and CD8+ T cell subsets (CD29+, CD45RO+ and CD29-, CD45RO-) was performed. RESULTS: Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues (28 of the 33). These EBS were present to a lesser extent in soluble cell fractions (11 of the 33). Immunostaining showed the estrogen receptor-positive cells to be the macrophage-like synoviocytes and the CD8+, CD29+ T cells both in RA and in control synovial tissues. Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells. CONCLUSION: It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage like synoviocytes, functioning as antigen-processing and antigen-presenting cells, and on antigen-experienced (memory) CD8+ T lymphocytes (CD29+, CD45RO+). PMID- 8343186 TI - Integrin-mediated attachment of articular chondrocytes to extracellular matrix proteins. AB - OBJECTIVE: To investigate the interactions between chondrocytes and their extracellular matrix (ECM). An attachment assay was used to determine the extent of integrin-mediated attachment of chondrocytes to a variety of ECM proteins and the effect of monolayer culturing on attachment activity. METHODS: Bovine and human articular cartilage chondrocytes were grown in high-density monolayer cultures for 3-21 days and used in the assays. Cell shape and production of 3H proline-labeled collagen were monitored to assess phenotypic changes with time in culture. Cultured chondrocytes were incubated in wells coated with purified proteins, with and without specific inhibitors of integrin-mediated attachment, and cell attachment was determined. RESULTS: Compared with bovine serum albumin, chondrocytes showed significant attachment to fibronectin, matrix Gla protein (MGP), osteopontin, bone sialoprotein II (BSP II), vitronectin, and types II and VI collagen. A synthetic peptide containing the integrin-recognition sequence Arg Gly-Asp inhibited attachment to all the proteins tested, except types II and VI collagen. A monoclonal antibody (MAb) to the beta 1-integrin subunit inhibited attachment to fibronectin, MGP, and type II collagen, and a MAb to the beta 3 integrin subunit inhibited attachment to BSP II and osteopontin. An increase in cell attachment was seen with time in culture, and this increase was followed by a change in the chondrocytes to flattened, type I collagen-producing cells. CONCLUSION: Chondrocytes can attach to a variety of cartilage and bone proteins; this attachment is mediated via integrins, including members of both the beta 1 and beta 3 subunit families. The modulation of the chondrocyte phenotype during monolayer culture may be related to activation or increased expression of integrins. PMID- 8343187 TI - Comparative studies of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with systemic lupus erythematosus. AB - OBJECTIVE: To investigate and compare the predisposing role of major histocompatibility complex (MHC) genes in systemic lupus erythematosus (SLE) in French Canadian and non-French Canadian (mainly Anglo-Saxon descent) Caucasian subjects. METHODS: HLA-A, B, C (serology), DR, and DQ (restriction fragment length polymorphism [RFLP] typing) were determined. RFLP defining a large C4A,21 OHA deletion (Taq I C4) and an Nco I tumor necrosis factor alpha (TNF alpha) RFLP were analyzed in 91 Caucasian Canadians and 91 ethnically matched control subjects. RESULTS: In the total SLE and non-French Canadian SLE populations, HLA B8, DR3(DR17), Dw24, DQ2, and the C4A gene deletion were associated with SLE. These HLA specificities and the C4A gene deletion were not significantly increased in French Canadian SLE patients compared with ethnically matched controls. When present in French Canadians, the C4A gene deletion was less closely associated with HLA-DR3(DR17), Dw24, DQ2 than in other Caucasians. HLA DQ6 was associated with SLE in French Canadians. No association of the 2-allele Nco I TNF alpha RFLP with SLE was found in this population, in either ethnic group. CONCLUSION: These results support the importance of ethnic background in the study of MHC genes and SLE. The extended HLA-B8,DR3,C4A null haplotype is found mainly in SLE patients of Anglo-Saxon descent, while the DQ6 specificity is associated with SLE in French Canadians. This relatively genetically homogeneous Caucasian population offers the opportunity to study non-HLA-B8,DR3-linked MHC influence in SLE. PMID- 8343188 TI - Lymphoproliferation in primary Sjogren's syndrome. Evidence of selective expansion of a B cell subset characterized by the expression of cross-reactive idiotypes. AB - OBJECTIVE: To evaluate the possibility that lymphoproliferation in primary Sjogren's syndrome (SS) arises within a subset of B cells. METHODS: A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)-associated cross reactive idiotypes (CRI) and anti-V kappa and anti-VH subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti-CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM-RF production by peripheral blood lymphocytes. The levels of CRI, IgM, and IgM-RF were quantitated in serum and culture supernatants by enzyme-linked immunosorbent assay. Heavy and light chain isotypes and VH subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting. RESULTS: Paraproteins from all patients expressed an epitope associated with V kappa IIIb sub-subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the V kappa IIIb-associated CRI (detected by MAb 17-109) and the VHI associated CRI (detected by MAb G6 and G8). None of the paraproteins expressed the VHIII-associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5-6 years. The anti-CRI and anti-subgroup antibodies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients. CONCLUSION: These results suggest that lymphoproliferation in primary SS is highly selective, and that the anti-CRI antibodies can be used as an aid to early diagnosis as well as for monitoring and modulating the lymphoproliferative process in primary SS. PMID- 8343189 TI - Antihistone antibodies in patients with localized scleroderma. AB - OBJECTIVE: To study the prevalence and antigen specificity of antihistone antibodies (AHA) in localized scleroderma. METHODS: Forty-nine serum samples from patients with localized scleroderma were examined by an enzyme-linked immunosorbent assay (ELISA) and by immunoblotting. RESULTS: By ELISA, AHA were demonstrated in 47% (23 of 49) of patients with localized scleroderma and in 87% (13 of 15) of patients with generalized morphea. Immunoblotting revealed that the predominant antigens were histones H1 and H3. The presence of AHA correlated with that of anti-single-stranded DNA antibody. CONCLUSION: Some of the major antigens for antinuclear antibodies in patients with localized scleroderma are histones. PMID- 8343190 TI - Connective tissue activation. XXXVI. The origin, variety, distribution, and biologic fate of connective tissue activating peptide-III isoforms: characteristics in patients with rheumatic, renal, and arterial disease. AB - OBJECTIVE: To determine the origin, distribution, and biologic fate of platelet derived connective tissue activating peptide-III (CTAP-III), to define the relative amounts of the antigen forms (CTAP-III, beta-thromboglobulin [beta-TG], neutrophil activating peptide-2 [NAP-2]) in plasma of normal persons and those with rheumatic or end-stage renal disease, and to define the isoforms of CTAP-III in platelets, plasma, transudates, and tissue deposits. METHODS: CTAP-III in plasma was measured by enzyme-linked immunosorbent assay, and growth promoting activity of CTAP-III isoforms was tested in synovial and peritoneal cell cultures by measuring increased synthesis of 14C-glycosaminoglycan (14C-GAG) and 3H-DNA. Isolated CTAP-III was characterized by Western blotting, microsequencing, and mass spectrometry. RESULTS: CTAP-III was the primary isoform of this antigen family in normal platelets and platelet-rich plasma; beta-TG and NAP-2 accounted for < 1% of CTAP-III isoforms. Previously undescribed isoforms, i.e., CTAP-III des 1, des 1-2, des 1-3, and a phosphate adduct of CTAP-III, were observed in varying amounts. Elevated plasma levels of CTAP-III antigen were found in a substantial fraction of rheumatic disease patients: 24% of those with rheumatoid arthritis, 36% of those with systemic sclerosis, and 15% of those with systemic lupus erythematosus. All 10 patients with end-stage kidney disease had marked elevations of plasma CTAP-III levels, which stimulated DNA and GAG synthesis by peritoneal cells in culture. Only large isoforms (such as CTAP-III) were detected in venous plasma of normal subjects, rheumatic disease patients, and patients receiving long-term dialysis. Normal human spleen and kidney contained substantial (micrograms/gm) amounts of CTAP-III and traces of an isoform with the electrophoretic mobility of CTAP-III des 1-15/NAP-2. Liver, lung, and urine contained lesser (ng/gm) amounts of CTAP-III. CONCLUSION: These data show that, among the 10 known isoforms, intact CTAP-III itself was the major circulating isoform (> 90%), and beta-TG was the most rare (0-1%). Deposition of CTAP-III in tissues, such as synovium, spleen, and kidney, is associated with partial processing to NAP-2-like isoforms and the potential to induce neutrophil and fibroblast activation in patients with rheumatic or end-stage renal disease. PMID- 8343192 TI - The spectrum of vasculitis in human immunodeficiency virus-infected patients. A clinicopathologic evaluation. AB - OBJECTIVE: To delineate the different types of inflammatory vascular diseases (IVD) occurring in patients with human immunodeficiency virus (HIV) infection. METHODS: Muscle, nerve, or skin biopsy specimens from 148 symptomatic HIV infected individuals were reviewed, and subgroups of vasculitis were identified using the American College of Rheumatology (ACR) 1990 clinicopathologic criteria for the classification of vasculitis. RESULTS: IVD was documented in 34 patients (23%) and included necrotizing arteritis (3 patients), non-necrotizing arteritis (1 patient), neutrophilic IVD (7 patients), mononuclear IVD (17 patients), and other small vessel inflammatory changes (6 patients). According to the ACR criteria, 11 patients could be classified as having a distinct category of vasculitis, including polyarteritis nodosa (4 patients), Henoch-Schonlein purpura (1 patient), and drug-induced hypersensitivity vasculitis (6 patients), and 23 were classified in the group "other vasculitis, type unspecified." One patient had hepatitis B virus surface antigenemia, 2 had cryoglobulinemia, and 2 were coinfected by human T lymphotropic virus type I. Cytomegalovirus inclusions and antigens were found in endothelial cells in 1 patient. HIV antigens and genome were detected in perivascular cells of 2 of the 3 patients with necrotizing arteritis; in 1, HIV-like particles were seen by electron microscopy. Immune deposits were found in small vessel walls in 5 skin biopsy samples showing small vessel vasculitis and in the muscle of the 3 patients with necrotizing arteritis. CONCLUSION: A wide range of inflammatory vascular diseases may occur in HIV infected individuals. Vascular inflammation appears multifactorial and may result from HIV-induced immunologic abnormalities and exposure to a variety of xenoantigens, such as HIV itself, other infectious agents, and drugs. PMID- 8343191 TI - Sensory nerves only temporarily protect the unstable canine knee joint from osteoarthritis. Evidence that sensory nerves reprogram the central nervous system after cruciate ligament transection. AB - OBJECTIVE: The slow rate at which articular cartilage degrades in dogs after transection of the anterior cruciate ligament (ACLT) has been attributed to capsular thickening and buttressing by osteophytes. We investigated the roles of the peripheral and central nervous systems in protecting knee joints with chronic ACL deficiency from breakdown. METHODS: Five groups of dogs were studied; all were killed 72 weeks after left knee surgery. Group A had ACLT, group B had ACLT followed 52 weeks later by ipsilateral L4-S1 dorsal root ganglionectomy (DRG), group C had DRG followed 2 weeks later by ACLT, group D had sham DRG followed 2 weeks later by ACLT, and group E had DRG followed 2 weeks later by sham ACTL. RESULTS: Group E dogs did not develop knee pathology. All cruciate-deficient knees were lax at the end of the study. The osteoarthritis (OA) that developed in groups A, B, and D was comparable (P > 0.05), and was significantly greater than that in group E (P < 0.05). Group C developed much more severe OA than any of the other groups (P < 0.05). CONCLUSION: Ipsilateral sensory input is temporarily important in protecting the unstable joint from rapid breakdown. Over time, the central nervous system apparently acquires the ability to protect the unstable joint without continued ipsilateral sensory input. PMID- 8343193 TI - The Chronic Arthritis Systemic Index: a nomogram to assess the activity and severity of chronic arthritis. PMID- 8343194 TI - Proteinuria associated with tolmetin treatment in a patient with systemic lupus erythematosus. PMID- 8343195 TI - Issues in the study of azathioprine, methotrexate, and combination therapy: comment on the article by Willkens et al. PMID- 8343197 TI - Food labeling: definition of the term 'healthy'. American Dietetic Association. PMID- 8343196 TI - In vitro phagocytosis inhibition assay for the screening of potential candidate antigens for sub-unit vaccines against the asexual blood stage of Plasmodium falciparum. AB - We have previously established a direct correlation between immune protection against the asexual blood stage Plasmodium falciparum infection and the presence of opsonizing antibodies promoting phagocytosis of parasitized red blood cells. In the present communication we describe an in vitro assay for measuring phagocytosis inhibition (PIA) specific for P. falciparum-infected erythrocytes. The phagocytosis inhibition assay is a simple procedure for screening potential candidates for sub-unit vaccines against P. falciparum based on the correlation between opsonizing antibodies and immunoprotection. The assay was used to analyse 18 recombinant molecules, corresponding to 11 distinct antigens of P. falciparum. Pre-incubation and selective antibody depletion experiments demonstrate the antigen-antibody specificity of the PIA. The presence of epitopes participating as targets of opsonic antibodies were demonstrated in six distinct polypeptide antigens. PMID- 8343198 TI - Clinical pharmacokinetics and practical applications of simvastatin. AB - Simvastatin is a methyl analogue of lovastatin and acts as an HMG-CoA reductase inhibitor effective in the treatment of hypercholesterolaemia. Like lovastatin, it is an inactive hydrophobic lactone prodrug which is metabolised in vivo to several more polar, pharmacologically active compounds, most notably the corresponding hydroxy acid form, simvastatin acid. HPLC techniques have been developed to assay simvastatin and its metabolites. In addition, a pharmacodynamic assay has been developed that measures HMG-CoA reductase inhibitory activity. This latter assay may be more applicable to clinical situations since simvastatin is not active, while its metabolites are. Simvastatin is well absorbed from the gastrointestinal tract but is highly extracted by the liver and only 7% of the dose reaches the general circulation intact. The peak inhibition of HMG-CoA reductase activity occurs within 2 to 4 hours. Increasing the dose of simvastatin from 5 to 120 mg increases the pharmacological activity in a linear fashion. The several metabolites tend to remain within the liver and the intestines (via biliary excretion). Some gastrointestinal reabsorption of metabolites may occur. Simvastatin is eliminated mainly in the faeces due to biliary excretion but only a small percentage of the dose is found in the stool in the form of the parent compound or simvastatin acid. Since simvastatin is metabolised by the cytochrome P450 system, a potential for drug interactions exists. Elevated HMG-CoA reductase inhibitory activity has been observed when simvastatin was administered concurrently with cyclosporin, possibly increasing the risk of myopathy and subsequent rhabdomyolysis which are associated with simvastatin use. Simvastatin has also been shown to potentiate the effects of warfarin [corrected].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343199 TI - Aluminum and hepatobiliary complications of total parenteral nutrition. PMID- 8343200 TI - Obesity experts say less weight still best. PMID- 8343201 TI - Laparoscopic surgery: more facts, less fancy. PMID- 8343202 TI - Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. AB - The retinoblastoma gene product (Rb) can interact efficiently with two of three D type G1 cyclins (D2 and D3) in vitro. Binding depended upon the minimal regions of Rb necessary for its growth-suppressive activity, as well as upon the D-type cyclin sequence motif shared with Rb-binding DNA tumor virus oncoproteins. Coexpression of the three D-type cyclins with the cyclin-dependent kinase (cdk4) in insect cells generated Rb kinase activity. By contrast, cyclins D2 and D3, but not D1, activated another such kinase, cdk2. Introduction of cyclin D2 and Rb into the Rb-deficient cell line SAOS-2 led to overt Rb hyperphosphorylation, whereas Rb, expressed alone or together with cyclin D1, remained unphosphorylated. Cyclin D2-dependent phosphorylation inhibited its binding to the transcription factor E2F and reversed the Rb G1 exit block in the cell cycle. Thus, all D-type cyclins do not function equivalently, and one of them plays a major role in reversing the cycle-blocking function of a known tumor suppressor. PMID- 8343204 TI - Every six hours a patient waiting for an organ dies. PMID- 8343203 TI - Three-dimensional structure of omega-conotoxin GVIA determined by 1H NMR. AB - omega-Conotoxin GVIA, a peptide of 27 amino acid residues and three disulfide bridges, has been studied by NMR techniques. The complete assignment of the corresponding proton NMR spectra was performed by two-dimensional sequence specific methods at 288 K and pH 3.5. On the basis of 169 distance restraints derived from this analysis, the three-dimensional structure was obtained. A total of 30 initial structures were generated by distance geometry methods and further refined by restrained energy minimization techniques yielding a final set of 8 structures. The mean root-mean-square deviation between each of the 8 structures and the mean atomic coordinates for all residues is 0.82 +/- 0.06 A for the backbone atoms and 1.45 +/- 0.18 A for all non-H atoms. The structure shows a globular folding pattern that is stabilized by the three disulfide linkages and a number of intramolecular hydrogen bonds. A total of 14 hydroxyl groups are found at the periphery fully exposed to the solvent. These groups, together with the charged side chains of Lys and Arg residues emerging radially from the peptide core, provide specific recognition elements for the interaction of this toxin with neuronal calcium channels. PMID- 8343205 TI - Immunosuppressive medications. PMID- 8343206 TI - Adult renal transplantation. PMID- 8343207 TI - Pancreas transplantation. PMID- 8343208 TI - Medical University of South Carolina Pediatric Renal Transplant Program. PMID- 8343209 TI - Chiral PAF agonists: synthesis, theoretical analysis of their stereoelectronic properties and structure activity relationships. AB - A series of chiral PAF agonists were synthesized. Modifications at the PAF structure were undertaken as far as the C2 substituents and the onium head groups are concerned. In parallel, molecular modelling studies including a MOPAC geometry optimization and the analysis of the electrostatic potential were performed on the newly synthesized and on already known PAF agonists, in order to gain a better insight into the stereoelectronic features required for interaction with the PAF receptor. PMID- 8343210 TI - Cinnamamide analogs as inhibitors of protein tyrosine kinases. AB - Protein tyrosine kinases (PTK) are important signal transducing enzymes involved in the modulation of normal cellular growth and differentiation and have been associated with the etiology of various human cancers. The development of properly designed inhibitors, which block their function by interfering with the substrate binding, may therefore offer an unique target for selective anticancer chemotherapy. Here we describe synthesis and biochemical testing of a novel series of non-peptide PTK inhibitors which have as characteristic active pharmacophore the cinnamamide moiety. For testing we used an exogenous substrate kinase assay based on the phosphorylation of (Val5)-angiotensin II with radiolabelled ATP by the catalytic domain of the PTK encoded by the v-abl oncogene (p45 v-abl). The most potent compounds were found in the class of 3 arylidene-2-oxindoles (II) with IC50 values in the 1 microM range. Among these the 2-tetralylmethylene-, 4-quinolylmethylene-, 5-quinolylmethylene- and 3 indolylmethylene-2-oxindole compounds of formulae 16, 20, 21 and 24 respectively were selected for further investigation. PMID- 8343211 TI - Chemical modifications of the antibiotic purpuromycin. AB - Purpuromycin, isolated in our laboratories from the culture broth of Actinoplanes ianthinogenes, is very active in vitro against Gram-positive bacteria and fungi and shows variable activity against Gram-negative bacteria. Its poor bioavailability, probably due to its insolubility in aqueous media at physiological pH's, and the fact that its activity is antagonized by serum, led us to plan a chemical program with the aim of understanding the relevance of the substituents for the antibiotic activity. The original 7-methoxycarbonyl group was transformed into more hydrophilic groups by hydrolysis, by reduction and by ammonolysis or in esters with different degree of lipophilicity and steric hindrance. Almost all of the derivatives retained activity against Gram-positive bacteria but lost activity against Escherichia coli and Trichophyton mentagrophytes. Like purpuromycin, all of the derivatives show a reduced activity in the presence of serum. PMID- 8343212 TI - Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. VI. Synthesis and preliminary pharmacological evaluation of 1-alkylaminomethyl-4,5-dihydro-s triazolo[3,4-d]-1,5-benzothiazepines. AB - A series of new 1-alkylaminomethyl derivatives of 4,5-dihydro-s- triazolo[3,4-d] 1,5-benzothiazepines has been prepared using chloromethyltriazolobenzothiazepines 4a-g as key intermediates. The 1-alkylaminomethyl derivatives were tested for CNS activity on mice and some of them caused remarkable decrease of spontaneous motor activity. PMID- 8343213 TI - In vitro metabolism of 1,3-dioxane, 1,3-oxathiolane, and 1,3-dithiane derivatives of theophylline: a structure-metabolism correlation study. AB - Correlation between structure and metabolism was studied within a series of cyclic acetal and thioacetal theophylline derivatives. All the compounds showed marked regioselectivity in in vitro metabolism, the metabolites arising only from 7-cycloalkyl side chain transformation. The 1,3-dioxane derivative, besides N dealkylation to theophylline, underwent enzymatic ring cleavage, through the oxidation of the acetal carbon and subsequent rearrangement. Thus the acetal group was converted enzymatically to an ester. A similar transformation, catalyzed by cytochrome P450-dependent monooxygenases, was previously found for the 1,3-dioxolane ring of doxophylline. The cyclic thioacetal derivatives (i.e. 1,3-oxathiolane and 1,3-dithiane) were not cleaved during oxidative metabolism. The metabolites arise only from the oxidation of the sulfur atom, the major nucleophilic center in the molecule. No N-dealkylation to theophylline was observed. Enzymatic sulfoxidation proceeded diastereoselectively in both the 1,3 oxathiolane and 1,3-dithiane rings, the trans isomers being the major ones with a ratio trans: cis 75:25 and 60:40 respectively. The sulfoxides were stable to hydrolysis and were not further metabolized. Neither disulfoxides nor sulfones were detected in the incubations. PMID- 8343214 TI - Synthesis and vasodilatory activity of some thiazolo-triazole derivative. AB - In this study, some thiazolo[3,2-b]-1,2,4-triazole derivatives were synthesized. Their vasodilatory activities were examined in vitro. All examined compounds showed appreciable activity. PMID- 8343215 TI - Coexistence of amyloid beta-protein precursor and basic fibroblast growth factor in single cells of the rat parietal cortex, hippocampus and basal magnocellular nucleus. AB - The coexistence of amyloid beta-protein precursor (APP) and basic fibroblast growth factor (basic FGF) in single cells of the parietal cortex, hippocampus and basal magnocellular nucleus was investigated immunohistochemically in adult rats. A monoclonal antibody directed against human recombinant APP and a polyclonal antibody against a synthetic fragment of basic FGF (the N-terminal 12 residues) were used. APP and basic FGF were frequently colocalized in the pyramidal cells of layers III and V of the parietal cortex, in the pyramidal and extrapyramidal cells of the hippocampus, and in large cells of the medial septal nucleus and the horizontal limb of the diagonal band of Broca. Such a frequent colocalization suggests a close functional relationship between APP and basic FGF in the neuronal cells. PMID- 8343216 TI - PPD-specific IgG and IgG subclasses in the sera of pulmonary tuberculosis patients. AB - This study was performed to characterize the humoral immune responses with isotype profiles in Mycobacterium tuberculosis infection. PPD-Specific IgG and IgG subclasses were measured using ELISA in 212 patients with pulmonary tuberculosis. The values of PPD-specific IgG were significantly higher in pulmonary tuberculosis patients than those in the control group, and were correlated to the severity of illness (P < 0.01). The specificity and sensitivity of ELISA for IgG antibodies were 1.0 and 0.81, respectively as determined in 212 sera from tuberculosis patients and 44 from healthy controls. The positive predictive value was 1.0 (171/171), while negative predictive value was 0.52 (44/85). The values of PPD-specific IgG were significantly decreased after 2-4 months of treatment. Among the moderately and far advanced pulmonary tuberculosis patients, the values of PPD-specific IgG were significantly decreased in responders after 6 months of treatment. However, PPD-specific IgG in nonresponders was increased (P < 0.01). PPD-specific IgG subclass responses were evident to all four IgG subclasses. No changes of isotype response according to the severity of the disease were observed. PMID- 8343217 TI - Impaired homeostatic mechanism of potassium handling after acute oral potassium load in diabetes mellitus. AB - Chronic stable diabetic patients (n = 6) were compared with healthy control subjects (n = 5) after acute oral intake of 50 mEq of potassium chloride (KCl) to investigate for possible derangements of homeostatic responses for acute term (3 hrs) to acute potassium load. Plasma renin activity (PRA), plasma aldosterone (PA), and transtubular potassium concentration gradient (TTKG) known as a useful semiquantative index of distal nephron potassium secretion were measured. All the baseline parameters were comparable between diabetic and non-diabetic subjects except for significantly reduced creatinine clearance in diabetics (mean +/- SEM, 105 +/- 4 vs. 85 +/- 5 ml/min, p < 0.05). Following acute oral KCl load, the peak increases of serum potassium changes from basal levels were noted at 2 hours in both groups, but were higher in diabetic subjects (mean +/- SEM, 0.42 +/- 0.06 vs. 0.62 +/- 0.09 mEq/L). Also, 4 out of 6 diabetic subjects but none of the control subjects at 2 hours after oral KCl load became hyperkalemic ( > 5.0 mEq/L). PRA did not show any significant changes, whereas PA was increased simultaneously with increments in serum potassium in both groups, with blunted increases in the diabetics. However, TTKG was increased prominently in control subjects (8.18 from 4.98), but only slightly in diabetic subjects (4.55 from 4.18), with statistical difference between the two groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343218 TI - Histological and immunohistochemical studies on primary gastrointestinal lymphomas. AB - To study the characteristics and histogenesis of the malignant lymphomas derived from the gastrointestinal mucosa, histologic and immunohistochemical analyses were performed on a series of 28 malignant lymphomas of the gastrointestinal tract. By cytomorphologic classification, there were two small lymphocytic lymphomas, one small cleaved cell lymphoma, two mixed small cleaved and large cell lymphomas, 17 large cell lymphomas, one small noncleaved cell lymphoma, three immunoblastic lymphomas, and two lymphoblastic lymphomas. This distribution of histologic types was compatible with that of nodal lymphoma. The lymphomas with poor prognostic histology (23 cases) outnumbered those with favorable prognosis (five cases). Three of 28 cases (one in the stomach and two in the small intestine) had cytologic features consistent with centrocytoid cell lymphoma of the mucosa associated lymphoid tissue and were large cell lymphomas. Immunophenotypically, 23 cases expressed B-cell markers (82.1%) and three cases reacted with T-cell markers. Two cases did not react with either T-cell or B-cell markers. True histiocytic lymphomas were not identified. Gastric lymphomas (nine cases) and colorectal lymphomas (three cases) were of B-lymphocyte origin whereas T-cell lymphomas were noted in the small intestine (two cases) and ileocecal region (one case). Three cases of centrocytoid lymphoma were of B-lymphocyte origin. Histologically B-cell lineage lymphomas were evenly distributed on various histologic subtypes but all T-lineage lymphomas belonged to the large cell type. The two cases with undetermined phenotype were lymphoblastic lymphomas histologically. This study showed that the primary GIT lymphomas, mostly of B cell lineage, were not cytomorphologically distinctive from the nodal lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343219 TI - Immunoelectron-microscopic localization of IgE binding site of mugwort pollen. AB - To elucidate the IgE binding site of mugwort (Artemisia vulgaris r.) pollen, pollen grains were frozen and fixed using a cryocut. They were incubated with antibodies according to the following sequence: Sera pool of individuals who showed mugwort-RAST class 3 or 4, biotin-labeled goat anti-human IgE antibody, streptavidin-peroxidase and diaminobenzidine. Then, they were observed under electron microscopy. The control section was incubated with the sera pool from individuals who showed a negative result on a skin prick test to mugwort pollen. Antigenic activity (electrondense line) was noted on the surface of the exine. There was no activity in cytoplasm or the intine layer. The control section was completely free of activity. It was suggested that the IgE binding site of mugwort pollen was present on the surface of the exine. PMID- 8343220 TI - Prevalence of otitis media and allied diseases in Korea--results of a nation-wide survey, 1991. AB - A nation-wide survey was conducted to estimate the prevalence of otitis media and allied diseases through physical examination by otolaryngologic doctors from July to October, 1991. A sample study population was selected from a panel to be representative of the Korean population by multistage clustered and stratified random sampling method based on the National Census Data, 1990. Total number of subjects undertaken were 9,321, Which were drawn from 2,899 households residing in 60 different areas throughout the country. The overall prevalence of otitis media was 2.85% (3.10% of males and 2.61% of females). Prevalence of each subtype was as follows; acute otitis media, 0.02%; middle ear effusion, 0.60%; chronic otitis media, 2.19%, respectively. The prevalence of otitis media did not vary by sex, nor by urban-rural difference. There was an increasing tendency of the prevalence of otitis media by age. However, the prevalence of both middle ear effusion and acute otitis media showed a decreasing pattern by age. Particularly noteworthy was a significant geographic variation in the prevalence of otitis media by provinces. The prevalence rate of septal deviation was 21.93% and the presence of septal deviation was significantly related to that of otitis media (p < 0.05). The prevalence rates of nasal allergic symptoms, nasal polyposis and evident cleft palate were 1.14%, 1.00% and 0.07%, respectively. The presence of otitis media was significantly correlated with both nasal allergic symptoms (P < 0.1) and evident cleft palate (P < 0.05), but not with that of nasal polyposis. PMID- 8343221 TI - Actions of potassium channel openers in rat detrusor urinae. AB - This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration dependently. P 1060, RP 49356 and BRL 38227 suppressed the maximal responses to bethanechol and shifted the concentration-response curves of bethanechol-induced contraction to the right. RP 49356 and BRL 38227 reduced the contraction by low (20 mM) concentration of potassium. P 1060, however, diminished the high (80 mM) and low (20 mM) concentration of potassium-induced contraction. Glibenclamide, an inhibitor of ATP-dependent potassium channel, antagonized the suppressive action of P 1060, RP 49356 and BRL 38227 on the basal tone. Apamin or procaine did not antagonize it significantly. Based on these results, it is suggested that the relaxation of detrusor muscle strip caused by P 1060, RP 49356 and BRL 38227 may predominantly involve opening of the same potassium channel, i.e., the ATP dependent potassium channel. PMID- 8343222 TI - Enhanced expression of the c-myc protooncogene in human intracranial meningiomas. AB - We examined the alteration and expression of c-myc protooncogene in 11 human intracranial meningiomas using Southern blot, Northern blot and immunohistochemical techniques. Southern blot showed neither amplification nor rearrangement but Northern blot and immunohistochemical study revealed enhanced expression of the c-myc gene. Immunohistochemically, c-myc product was found in all of the 11 cases and seven of these cases showed an above moderate degree of immunoreaction in semiquantitative analysis. Loss of heterozygosity at IGLC2 locus on chromosome 22 was detected in four of the 8 informative cases. But extent and intensity of immunoreactivity did not correlated with loss of heterozygosity on chromosome 22. These genetic changes may play important roles in the pathogenesis of human intracranial meningioma. PMID- 8343223 TI - Loss of retinoblastoma gene and amplification of N-myc gene in retinoblastoma. AB - We have analyzed paired samples of genomic DNA from peripheral leukocyte and primary tumor tissue from nine patients with retinoblastoma (RB) and from two RB cell lines, WERI-Rb-1 and Y79, to detect the molecular alterations of the retinoblastoma susceptibility gene (RB-1) and N-myc gene. In Southern analysis, RB-1 deletions in tumor tissues were detected in five patients (56%), one of these revealed a total loss of RB-1. N-myc amplification was found only in one (11.1%) out of nine patients. We also observed a total loss of RB-1 in WERI-Rb-1, and a more than 100-fold amplification of N-myc in Y79. The analysis of the relationship between molecular events and clinical characteristics such as age, sex, tumor laterality did not reveal any specific correlation. These results suggest that genetic backgrounds of RB in Korean patients are quite similar to those of reported cases elsewhere. The high sensitivity of our method in detecting the RB-1 loss indicates that this method can be a useful tool for initially screening a large number of tumors. PMID- 8343224 TI - Evaluation of outcome after acute carbon monoxide poisoning by brain CT. AB - Of 129 patients with carbon monoxide (CO) poisoning, 62(48.0%) had characteristic computed tomographic (CT) findings. The most common finding, seen in 42 patients, was low-density in the cerebral white matter, and the second characteristic feature, seen in 33 patients, was low-density in both globus pallidi. Abnormal CT findings tended to increase in accordance with the duration of unconsciousness during acute CO poisoning, but such findings occurred even when the mental state was clear during acute illness. The prognosis of acute CO poisoning depended on low-density lesions of the cerebral white matter rather than those of the globus pallidus. There also seemed to be a significant correlation between the cerebral white matter changes in the initial CT scan and the development of delayed neurologic sequelae after acute CO poisoning, particularly in middle age or older patients, but no correlation between the CT findings and the clinical outcome of delayed neurologic sequelae. PMID- 8343225 TI - Comparison of enzyme and DNA analysis in a Tay-Sachs disease carrier screening program. AB - Tay-Sachs disease (GM2 gangliosidosis, type 1; TSD) is an autosomal recessive GM2 gangliosidosis resulting from the deficient activity of the lysosomal hydrolase beta-hexosaminidase A (Hex A). With a carrier frequency estimated at 1 in 25, it is a common lysosomal disorder in the Ashkenazi Jewish population. Tay-Sachs disease has provided the prototype for the prevention of severe recessive genetic diseases. Molecular analysis of the Hex A gene (HEXA) of Ashkenazi Jewish individuals affected with Tay-Sachs disease revealed that three common mutations cause the infantile and adult onset forms of the disease; a four base insertion in exon 11, a splice junction mutation in intron 12 and a point mutation in exon 7 (G269S). A study was undertaken to determine whether mutation analysis would be useful in TSD screening programs in identifying carriers and clarifying the status of individuals whose enzyme assays are inconclusive. Ashkenazi Jewish individuals who had been diagnosed as carriers, inconclusives by enzyme assay and non-carriers with low normal enzyme levels in the Mount Sinai Tay-Sachs Disease Prevention Program were examined for the presence of the three mutations using polymerase chain reaction (PCR) and allele specific oligonucleotide (ASO) hybridization. The insertion mutation was present in 29 of 34 carriers and 2 of 36 inconclusive individuals, the splice junction mutation was found in 4 of 34 carriers and the G269S mutation was found in 1 of 34 carriers. Of the 313 non carrier individuals with normal enzyme activity in the lower normal range, one was positive for the splice junction mutation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343226 TI - Regulation of the urinary excretion of endothelin in the rat. AB - The regulation of the urinary excretion of endothelin (UETV) and its clinical significance has not yet been established. The present study was designed to examine the effect of angiotensin II (A-II), arginine vasopressin (AVP), and nifedipine on UETV. Anesthetized Munich-Wistar rats were infused with low (50 ng/kg/min) and high (500 ng/kg/min) doses of A-II for 30 min. Both doses significantly increased UETV, from nondetectable (ND) levels to 155 +/- 54 (P < .03) and 450 +/- 86 fg/min (P < .001), respectively. This effect was accompanied by a significant increase in urine flow (UV), from 6 +/- 1 to 67 +/- 12 and 89 +/ 10 microL/min, and in mean arterial pressure (MAP), from 139 +/- 4 to 187 +/- 5 and 217 +/- 3 mm Hg. Infusions of A-II with its nonspecific antagonist, saralasin, resulted in a further increase in UETV to 647 +/- 126 and 782 +/- 117 fg/min (P < .002), respectively. However, infusion of A-II with its specific antagonist, losartan, completely blocked its stimulatory effect on UETV. Infusion of AVP, 10 or 100 mU/kg/h, produced increases in MAP, from 134 +/- 3 to 165 +/- 7 and 203 +/- 4 mm Hg, and in UV from 6 +/- 1 to 37 +/- 6 and 97 +/- 17 microL/min, comparable to A-II, but AVP did not have a marked effect on UETV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343227 TI - Abnormalities in dihomo-gamma-linolenic acid release in the pathogenesis of hypertension. AB - Spontaneously hypertensive rats (SHR) respond to angiotensin and norepinephrine with an exaggerated pressor response. We have investigated the possibility that increased vascular reactivity in SHR may be related to a reduced synthesis of prostaglandin E1 (PGE1) resulting from a defect in the release of its precursor, dihomo-gamma-linoleic acid (DGLA). Isolated perfused mesenteric vascular beds of SHR and age matched Wistar-Kyoto rats (WKY) were perfused with Kreb's bicarbonate buffer. The effluent was collected and the fatty acid composition determined by gas chromatography. In SHR the release of DGLA, arachidonic acid, eicosapentaenoic acid, and virtually all other fatty acids detected in the effluent were reduced when compared to their normotensive controls. This difference could not be explained by low tissue fatty acid levels because these were higher in SHR. Evening primrose oil (EPO) when added to the diet increased the release of DGLA but not of other prostanoid precursors. EPO also reduced vascular reactivity and reduced blood pressure in SHR. It is suggested that the defect in the release of DGLA may be involved in the pathogenesis of hypertension because it occurs early before hypertension has actually occurred. PMID- 8343229 TI - Effects of neurotensin on norepinephrine release in blood vessels of spontaneously hypertensive rats. AB - The present study was performed to investigate the effects of neurotensin on noradrenergic transmission in blood vessels of hypertension. In the perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats, we examined the influences of neurotensin on vascular responsiveness and norepinephrine release from adrenergic neurons. In studies with male standard Wistar rats, endogenous norepinephrine release during periarterial nerve stimulation was inhibited by neurotensin in a dose-dependent manner. Vasoconstrictor responses to electrical nerve stimulation were also inhibited by neurotensin. In SHR, the stimulation-evoked pressor responses and norepinephrine release were enhanced compared with WKY rats. The suppression of these responses by neurotensin was significantly less in SHR than in WKY rats. These results show that neurotensin could have a modulatory effect on noradrenergic activity and cause a decrease in stimulation-evoked norepinephrine release from vascular adrenergic neurons. The lesser reduction of pressor responses and norepinephrine release by neurotensin in SHR might suggest an insufficient regulation of vascular adrenergic transmission by the peptide hormone in hypertension. PMID- 8343228 TI - Possible radical scavenging properties of cicletanine and renal protection in Dahl salt sensitive rats. AB - Much interest in cicletanine, a novel antihypertensive drug, has grown because it uniquely stimulates prostacyclin (PGI2) production and may, thereby, provide further cardiovascular protection. We postulated that cicletanine may be an antioxidant, and assessed its ability to protect the kidney in Dahl salt sensitive (Dahl S) rats on a high salt diet. Cicletanine eradicated in vitro a stable radical, DPPH, and decreased the lipid peroxidation both in rat brain homogenate and in a xanthine-xanthine oxidase (X-XOD) superoxide generating system. Furthermore, cicletanine attenuated the inhibition of PGI2 synthase activity by 15HPETE. However, cicletanine did not exhibit superoxide dismutase like activity in X-XOD system, suggesting that it behaves primarily as a hydroxy radical scavenger. A 6 week cicletanine treatment reduced blood pressure in Dahl S rats fed a high salt diet, and ameliorated functional and morphological injury to the kidney. This attenuation of glomerular sclerosis correlated with the attenuation of lipid peroxidation in the kidney homogenate. These data indicate that cicletanine is an antioxidant that protects the kidney from salt-induced hypertension in Dahl salt-sensitive strain rats. PMID- 8343230 TI - Blood pressure variability and urinary electrolyte excretion in normotensive adults. AB - The principal aim of the present study was to determine the relationship of ambulatory blood pressure (BP) to urinary electrolyte excretion in normotensives. Twenty-five young adults underwent ambulatory BP and heart rate monitoring while collecting urine over 24 h. The correlations of 24 h urine sodium excretion and the ratio of sodium/potassium excretion with systolic BP in the laboratory (r = 0.12 and 0.24), ambulatory awake (r = 0.11 and 0.24), and ambulatory asleep (r = 0.24 and 0.31) settings were all in the positive direction but not significant. However, 24 h sodium excretion did correlate significantly and positively with awake and asleep ambulatory systolic (r = 0.45 and 0.41, P < .05) and diastolic (r = 0.42 and 0.43, P < .05) coefficients of variability. Thus, in normotensives on an unlimited diet, 24 h urinary sodium was more closely related to ambulatory BP variability than to BP level. PMID- 8343231 TI - Myocardial fibrosis in the rat with mineralocorticoid excess. Prevention of scarring by amiloride. AB - In both humans and experimental animals, mineralocorticoid (MC)-induced hypertension is associated with myocardial fibrosis. We have shown that this fibrous tissue response includes a reactive interstitial fibrosis not initiated by parenchymal cell loss, and a reparative fibrosis or scarring, occurring in response to cardiac myocyte necrosis. The reactive fibrosis is thought to be related to MC excess, while cell loss and microscopic scarring may be secondary to enhanced potassium excretion or a cytotoxic effect of aldosterone. This histologic study was undertaken to determine whether or not the potassium sparing diuretic amiloride would be effective in preventing the appearance of either form of fibrosis. Uninephrectomized male Sprague Dawley rats received either aldosterone (AL; 0.75 microgram/h), amiloride (AMC; 1 mg/kg/day), aldosterone+amiloride (ALAM), or vehicle (ALC) alone via subcutaneous osmotic minipumps for 8 weeks. All rats received 1% NaCl in their drinking water. Hearts were recovered, immersion-fixed, and tissue sections from both left and right ventricles stained with the collagen specific stain Sirius Red F3BA were morphometrically analyzed. The interstitial collagen volume fraction was elevated in AL and ALAM groups compared to ALC and AMC, but did not differ between AL and ALAM. Microscopic scarring, found in both ventricles, was evident in AL animals, but was not found in the ALAM, AMC, or ALC groups. These data suggest that chronic elevations in plasma aldosterone, relative to dietary sodium intake, do not have a direct cytotoxic effect on cardiac myocytes, but they are associated with a reactive interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343232 TI - Synergistic action of angiotensin II, insulin-like growth factor-I, and transforming growth factor-beta on platelet-derived growth factor-BB, basic fibroblastic growth factor, and epidermal growth factor-induced DNA synthesis in vascular smooth muscle cells. AB - The effect of angiotensin II (AII), transforming growth factor-beta (TGF-beta), and insulin-like growth factor-I (IGF-I) on platelet-derived growth factor (PDGF) BB-, basic fibroblastic growth factor (bFGF)-, and epidermal growth factor (EGF) induced DNA synthesis in vascular smooth muscle cells (VSMCs) was investigated. TGF-beta, AII, IGF-I increased concentration-dependent cell protein. No increase in [3H]thymidine incorporation could be detected. TGF-beta, AII, and IGF-I enhanced PDGF-BB-, bFGF-, and EGF-induced DNA synthesis. Our results suggest that growth factors that possess a weak mitogenic effect on vascular smooth muscle cells such as TGF-beta, AII, and IGF-I may enhance the mitogenicity of PDGF-BB, bFGF, and EGF. PMID- 8343233 TI - Impaired recovery of vascular smooth muscle intracellular calcium following agonist stimulation in insulin resistant (Zucker obese) rats. AB - We have previously shown that insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle cell (VSMC) Ca(2+)-ATPase mediated Ca2+ efflux and vascular relaxation. We have now sought to determine if VSMC from insulin resistant (Zucker Obese, ZO) rats manifest exaggerated [Ca2+]i responses to pressor agonists and impaired [Ca2+]i recovery (rate of [Ca2+]i return to baseline) compared to their lean controls (ZL). Thoracic aortae from ZO and ZL were enzymatically digested to release VSMC (n = 16 animals/group and 8 determinations/group). Freshly dispersed cells were washed, counted, and loaded with Fura-2-AM. The [Ca2+]i responses to and rate of recovery from angiotensin II (AII; 200 nmol/L) and arginine vasopressin (AVP; 10 mumol/L) were studied fluorometrically in stirred suspension (10(6) cells/mL). Peak [Ca2+]i responses to AVP were not significantly different in ZO v ZL, while responses to AII were higher in ZL ([Ca2+]i, 180 +/- 7 v 160 +/- 4% of baseline in ZL and ZO, P < .02). Since we have recently shown insulin to increase AII-releasable Ca2+ stores in sarcoplasmic reticulum, this increase in peak [Ca2+]i response to AII in ZL may reflect relative VSMC insulin resistance in ZO. Despite their increased peak AII response, ZL exhibited a more rapid recovery from both the AII-stimulated load (recovery rate, 66.1 +/- 8.9 v 42.1 +/- 9.0 nmol/L/min in ZL and ZO, P < .02) and the AVP-stimulated [Ca2+]i load (22.2 +/- 2.3 v 18.4 +/- 4.6 nmol/L/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343234 TI - Determinants of left ventricular mass in normotensive children. AB - Left ventricular hypertrophy has been shown to be an independent predictor of cardiovascular morbidity and mortality. Few studies have examined the determinants of left ventricular mass (LVM) in normotensive children. Eight-four healthy children, blacks and whites, girls and boys, between 6 and 18 years of age, all with positive family histories of essential hypertension, participated in the study. Demographic and anthropometric characteristics, physical activity, and hemodynamic responses at rest and in response to the stress of forehead cold stimulation and a challenging video game were related to M-mode echocardiographic determined LVM indexed by two indices of body habitus. Hierarchical stepwise multiple regression analysis indicated that the significant independent correlates of LVM per body surface area were gender (boys were greater), baseline systolic blood pressure and heart rate, a physical activity index (sweat episodes per week) and peak systolic blood pressure responses to the forehead cold stressor (final model r2 = 0.49). For LVM/height2.7 significant independent correlates were adiposity index (weight z score--height z score), gender (boys were greater), age, resting systolic pressure, and systemic vascular resistance reactivity to forehead cold stimulation (final model r2 = 0.42). These findings with normotensive children corroborate other findings that have typically involved hypertensive children, indicating that resting heart rate and systolic pressure, gender, and adiposity are early determinants of LVM indices in children. In addition, the current findings indicate that hemodynamic responses to stress also appear to play a role in the early development of LVM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343235 TI - Effects of renin inhibitor A-72517 on hemodynamics and cardiac function in sodium depleted dogs. AB - A-72517 is a potent inhibitor of human renin (IC50 = 1.0 nmol/L, pH 7.4 in plasma) and, aside from displaying modest activity against canine plasma renin (IC50 = 110 nmol/L), has been shown to be orally active in the dog and other animals. Renin inhibitors, in general, are presumed to exert their hypotensive effect through a reduction in total peripheral resistance. To elucidate the hemodynamic mechanism of action of this new dipeptidic renin inhibitor, the cardiac and systemic hemodynamic effects of A-72517 were studied in sodium depleted, pentobarbital-anesthetized dogs. Each dog received either vehicle (n = 8) or a single dose (n = 8/dose) of A-72517 administered intravenously as a priming bolus followed by a 30 min constant infusion; infusion doses were 0.01, 0.05, and 0.1 mg/kg/min. A-72517 elicited significant (P < .05) dose-related reductions in mean arterial pressure (MAP) and systemic vascular resistance (SVR) compared to baseline values and the vehicle-treated group, and the recoveries of MAP and SVR were also dose-related. Plasma renin activity, measured by radioimmunoassay, was nearly completely suppressed during drug infusion at all doses. The hypotensive responses did not alter cardiac output nor did they induce reflex tachycardia at any dose. Left ventricular dP/dtmax did not change during infusion of A-72517, but, when corrected for changes in afterload, showed dose related increases with drug treatment. Moreover, left ventricular end-diastolic pressure and pulmonary arterial wedge pressure were significantly reduced at the high dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343236 TI - Calcium metabolism, plasma parathyroid hormone, and calcitriol in transient hypertension of pregnancy. AB - In order to know if abnormalities of calcium metabolism may be involved in the pathophysiology of pregnancy-induced hypertension (PIH), as it has been incriminated in essential hypertension, we measured plasma and urinary calcium and phosphate as well as plasma PTH and free calcitriol index (ratio of total calcitriol on the D binding protein) in normotensive pregnant women (n = 25), in women with PIH after the same duration of amenorrhea (> 28 wk, n = 21:preeclampsia and 20 transient hypertensions), and in age-matched nonpregnant women (n = 15). The severity of PIH was mild since blood uric acid was not increased and plasma volume, measured with the Evans blue technique, was found only moderately decreased (-10.5 +/- 3.1% of normal value). The results show that normotensive pregnant women showed the expected increase of the vitamin D parameters in comparison to nonpregnant controls. Hypertensive pregnant women were not different from the normotensive ones regarding plasma corrected calcium and phosphate and urinary excretion of calcium and phosphate, but had higher plasma PTH (13 +/- 1 v 8.8 +/- 1.6 pg/mL) and lower total and free calcitriol index (86 +/- 7 v 110 +/- 6 pg/mL and 1.72 +/- 0.10 v 2.25 +/- 0.13 x 10(-5)). Correlative studies showed PIH having a negative correlation between blood pressure and plasma corrected calcium (r = -0.43, P < .05), which is in agreement with epidemiological studies of essential hypertension. In conclusion, disturbances of calcium regulating hormones do exist in transient forms of pregnancy-induced hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343237 TI - Potassium channel antagonists and vascular reactivity in stroke-prone spontaneously hypertensive rats. AB - The goal of this study was to characterize differences in contractile responsiveness to several potassium channel antagonists in vascular smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY). Helically-cut strips of carotid arteries (endothelium removed) from SHRSP and WKY were mounted in muscle baths for measurement of isometric force generation. Contractile responses to tetraethylammonium (10(-4) to 3 x 10(-2) mol/L) and barium (3 x 10(-5) mol/L), blockers of the voltage dependent and large conductance, calcium activated potassium channels, were greater in carotid arteries from SHRSP than in those from WKY. In contrast, contractile responses to the voltage-dependent potassium channel blockers 3,4 diamino-pyridine (10(-6) to 3 x 10(-3) mol/L) and sparteine (10(-6) to 3 x 10(-2) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid arteries from SHRSP and WKY did not contract to apamin (10(-9) to 10(-6) mol/L), an antagonist of the small conductance, calcium activated potassium channel. Furthermore, relaxation responses to diazoxide (3 x 10(-4) mol/L), an activator of the ATP-sensitive potassium channel, and subsequent contractions to the ATP sensitive potassium channel blocker glyburide (10(-8) to 3 x 10(-6) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid artery segments from SHRSP were more sensitive to the contractile effects of elevated potassium than those from WKY. We conclude that altered activity of the large conductance, calcium activated potassium channel may play a role in the increased responsiveness observed in arteries from SHRSP. PMID- 8343238 TI - Erythrocyte Na+/Li+ countertransport and glomerular hyperfiltration in insulin dependent diabetics. AB - Erythrocyte Na+/Li+ countertransport activity was investigated in 11 controls and 22 recent onset type I (insulin-dependent) diabetic patients with normal and high glomerular filtration rates. No differences in Vmax were observed in hyperfiltering compared to normofiltering patients or controls. The Na+/Li+ activity was correlated with blood glucose levels in insulin-dependent diabetics showing good glycemic control. Total cholesterol and triglyceride concentrations were similar among the three groups. In conclusion, enhanced Na+/Li+ countertransport activity is not associated, in our case, with diabetic condition per se and with early glomerular hyperfiltration and cannot be used as a marker of renal involvement in recent onset insulin-dependent diabetics. PMID- 8343239 TI - Differential regulation of ANF-R2 receptors coupled to adenylyl cyclase in cardiovascular tissues in hypertension. AB - We have recently shown that ANF-R2 receptors are coupled to the adenylyl cyclase/cAMP system through inhibitory guanine nucleotide regulatory protein (Gi). The present studies were undertaken to investigate the regulation of ANF-R2 receptor-mediated inhibition of adenylyl cyclase in spontaneously hypertensive rats (SHR) which have been reported to have high plasma ANF levels. ANF99-126 inhibited adenylyl cyclase activity in a concentration dependent manner in both aorta and heart sarcolemma from SHR and age-matched Wistar-Kyoto (WKY) rats, however, the extent of inhibition was greater in SHR as compared to WKY. On the other hand, ANF99-126 also inhibited the adenylyl cyclase activity in rat platelets from WKY rats in a concentration dependent manner, however, the inhibition in SHR was completely attenuated. In addition GTP gamma S stimulated adenylyl cyclase activity by about 600% in aorta from WKY rats and about 300% in SHR. On the other hand, the GTP gamma S-stimulated adenylyl cyclase activity was higher in platelets from SHR as compared to WKY. The observed difference may be attributed to the differential alterations in ANF-R2 receptor number or postreceptor events or both. Nonetheless, these results indicate that ANF-R2 receptors in platelets from SHR are differentially regulated than those in heart and aorta. PMID- 8343240 TI - Ionized magnesium and calcium levels in umbilical cord serum of pregnant women with transient hypertension during labor. AB - Using a new ion selective electrode (ISE) to measure ionized magnesium (IMg2+), we compared levels of IMg2+ with total magnesium (TMg) and serum ionized calcium levels (ICa2+) in umbilical arterial and venous serum of 13 parturients who developed transient hypertension in labor with levels in 38 who remained normotensive. Ionized, but not total magnesium levels were significantly lower in the umbilical veins of the hypertensive compared to the normotensive subjects (0.46 +/- 0.01 v 0.51 +/- 0.01 mmol/L), and these were at least 15% lower than maternal levels found in nonpregnant women (0.60 +/- 0.005 mmol/L, P < .001). If umbilical vein samples reflect maternal levels as well, then these results suggest that lower IMg2+ levels may play a role in the development of transient hypertension in labor, and the potential utility of an ion selective electrode for ionized magnesium in the diagnosis of subtle magnesium deficient states. PMID- 8343241 TI - Size of endotracheal tube and neonatal acquired subglottic stenosis. Study Group for Neonatology and Pediatric Emergencies in the Parisian Area. AB - OBJECTIVE: Risk factors for acquired laryngotracheal stenosis in newborn infants are poorly known. The extreme scarcity of acquired laryngotracheal stenosis in young infants in France, compared with the published rate in the English literature, suggested that these patients may be treated in a different way in France. A prospective study was performed to analyze local features. DESIGN: Six month multicenter inception cohort study. SETTING: Seven neonatal intensive care units of referral centers in the area of Paris, France. PATIENTS: A total of 247 intubated surviving neonates in a consecutive sample during 6 months. INTERVENTION: A file was completed with sex, birth weight, gestational age, underlying disease, and every feature concerning the intubation period and the outcome. MAIN OUTCOME MEASURES: All the collected data were compared with those available from previous studies in the English literature. RESULTS: After extubation, respiratory outcome was uncomplicated in 242 cases. The five patients with dyspnea were treated medically and recovered. A much higher rate of extubation difficulties was reported in the English literature. The rate of stenosis in this series was significantly lower than in previously reported studies. The differences between this and other series seem to be higher birth weights, shorter duration of intubation, and, most important, a smaller tube size (2.5 mm in neonates weighing less than 2500 g and 3.0 mm in those weighing 2500 g or more). CONCLUSIONS: Although this is a limited series and many unknown variables can differ from those in previous studies, the size of the endotracheal tube appears to be a major risk factor for acquired laryngotracheal stenosis in the neonate. Further studies seem necessary to point out additional factors. PMID- 8343242 TI - Bacteriology and immunology of normal and diseased adenoids in children. AB - Adenoid physiology as reflected in the qualitative and quantitative bacteriology and immune cell distribution was correlated with clinical presentation in 69 children (16 to 130 months of age) undergoing adenoidectomy for obstructive adenoid hyperplasia (n = 38) or chronic adenoid infection (n = 31) and in 16 adenoid core biopsy specimens from 16 nondiseased controls. In the control adenoids, few potentially pathogenic bacteria were found as the dominant bacteria in the adenoid core (25%), and significantly greater concentrations of nonpathogens (commensals) were isolated (P < .01). Potential pathogens as the dominant bacteria were found twice as often in obstructive adenoid hyperplasia (62%) and in chronic adenoid infection (55%) (P < .05). Haemophilus influenzae was most common in the diseased adenoids, 53% in obstructive adenoid hyperplasia and 48% in chronic adenoid infection, compared with only 19% in the controls (P < .05). No significant differences in lymphocyte density, B and T cells, as well as T-helper subsets, were found between clinical classifications. However, T suppressor cells, monocytes-macrophages, and natural killer cells were significantly increased in chronic adenoid infection only (P < .05). The findings in this study support roles for both alterations in bacterial homeostasis and an altered immune profile in the etiology of chronic adenoid disease in children. PMID- 8343243 TI - Bacterial allergy in nasal polyposis. A new method for quantifying specific IgE. AB - OBJECTIVES: To determine (1) if bacteria-specific serum IgE levels can be more effectively measured by first absorbing competing IgG antibodies from serum and (2) if patients with chronic paranasal sinus disease exhibit a high positive prevalence of bacteria-specific serum IgE. DESIGN: A modified radioallergosorbent test method was employed wherein each serum sample was absorbed with recProtein A to remove competing non-IgE antibodies, and purified proteins extracted from 16 individual bacteria were used as potential allergens. PARTICIPANTS: Twenty-four patients with nasal polyposis and 14 with chronic sinusitis, all refractory to conventional medical therapy and requiring endoscopic sinusotomies, were tested. Tested as controls were 10 subjects with chronic allergic rhinitis, without a history of chronic sinus disease, and possessing total serum IgE and inhalant specific IgE levels equal to or higher than the patient group. RESULTS: (1) Pretreatment of serum samples with recProtein A resulted in an increase of bacteria-specific radioallergosorbent test sensitivity. (2) Seventeen of 24 patients with polyps, eight of 14 with chronic sinusitis, and one of 10 with chronic allergic rhinitis were determined to be IgE positive when tested with this assay. CONCLUSIONS: (1) Bacteria-specific serum IgE can be quantified; (2) most patients with nasal polyposis and/or chronic sinusitis possess bacteria specific IgE in their serum, while subjects with only allergic rhinitis do not; and (3) multiple bacterial species isolated from chronically infected sinuses are capable of inducing IgE-mediated sensitization. PMID- 8343244 TI - Embolization for the treatment of posterior epistaxis. An analysis of 31 cases. AB - Thirty-one patients with posterior epistaxis refractory to nasal packing alone or in combination with surgical ligation (n = 8) underwent diagnostic angiography and therapeutic embolization of the internal maxillary artery. Embolization resulted in the cure of epistaxis in 22 cases (71.0%). Of the nine failures (29.0%), seven underwent successful surgical clipping of the ethmoid arteries, and two were treated conservatively and died of their primary hematologic disease within 33 days. Late rebleeding occurred in two patients: one underwent re embolization and the other was treated surgically. No severe or permanent complications occurred. The results indicate that embolization is a feasible alternative to surgical intervention for patients with posterior epistaxis, and we recommend it as the treatment of choice in cases with high surgical risk or failure of prior arterial ligation. PMID- 8343245 TI - Use of alprazolam for relief of tinnitus. A double-blind study. AB - OBJECTIVE: To systematically test the effectiveness of alprazolam as a pharmacological agent for patients with tinnitus. DESIGN: Prospective, placebo controlled, double-blind study. PATIENTS: Forty adult patients with constant tinnitus who had experienced their tinnitus for a minimum of 1 year and who resided in the Portland, Ore, metropolitan area. Twenty patients were randomly assigned to the experimental group and 20 to the control group. RESULTS: Seventeen of 20 patients in the experimental (alprazolam) group and 19 of the 20 in the placebo (lactose) group completed the study. Of the 17 patients receiving alprazolam, 13 (76%) had a reduction in the loudness of their tinnitus when measurements were made using a tinnitus synthesizer and a visual analog scale. Only one of the 19 who received the placebo showed any improvement in the loudness of their tinnitus. No changes were observed in the audiometric data or in tinnitus masking levels for either group. Individuals differed in the dosages required to achieve benefit from the alprazolam, and the side effects were minimal for this 12-week study. CONCLUSIONS: Alprazolam is a drug that will provide therapeutic relief for some patients with tinnitus. Regulation of the prescribed dosage of alprazolam is important since individuals differ considerably in sensitivity to this medication. PMID- 8343246 TI - The National Temporal Bone, Hearing, and Balance Pathology Resource Registry. AB - The National Temporal Bone, Hearing, and Balance Pathology Resource Registry has been established with funding provided by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health. The registry is meant to serve as a national resource for researchers and the public to stimulate and facilitate human otopathologic research. It will maintain a computerized database of currently active and inactive temporal bone and auditory brain-stem collections throughout the United States. In addition, it will encourage human temporal bone research by disseminating pertinent information, developing and fostering temporal bone professional educational activities, implementing a national temporal bone acquisition network, and encouraging investigative collaborations in the study of the human temporal bone and brain structures. It will also identify otopathologic collections at risk of being discarded or lost and will develop mechanisms and strategies to conserve them. PMID- 8343247 TI - The concept of transtympanic injection of fibrin caulk. AB - Cerebrospinal fluid otorhinorrhea after basilar skull trauma poses a difficult management problem. When conservative techniques fail, more aggressive neurosurgical and otologic procedures are required to control cerebrospinal fluid leakage. We assessed a less invasive method for the repair of traumatic cerebrospinal fluid fistulas. Thirty-one adult Sprague-Dawley rats were used to develop an animal model for the treatment of cerebrospinal fluid leakage. A fistula was created by removing a thin plate of bone from the superior aspect of the rat bulla. The bulla was then plugged with a transtympanic injection of fibrin caulk. Otoscopic and histologic data were collected at selected intervals. Transtympanic injection of fibrin caulk failed to alter significantly the rate of healing of cerebrospinal fluid fistulas. Coagulum retraction, rapid fibrinolysis, and other reasons for failure are explored. PMID- 8343248 TI - Transiently evoked and distortion-product otoacoustic emissions. Comparison of results from normally hearing and hearing-impaired human ears. AB - Evoked otoacoustic emissions can be measured after a transient stimulus or as distortion products of two pure tones. Measurements of both emission types are being used more frequently as the techniques become easier to implement and the clinical benefits are realized. In addition, comparisons between the two types of emissions from the same ear provide information about cochlear mechanisms. We have measured transiently evoked otoacoustic emissions (TEOAEs) stimulated with clicks and distortion-product otoacoustic emissions (DPOAEs) from 166 ears of individuals with and without hearing impairment. The TEOAE and DPOAE amplitudes were compared with each other and with corresponding audiometric thresholds by frequency. Results revealed a high correspondence between the two emission types (r = .78) and between the distribution of the energy for each emission and audiometric threshold levels at corresponding frequencies (DPOAE, Spearman p = .84; TEOAE, p = -.77). The DPOAEs were present more often than were TEOAEs when hearing levels across frequency were greater than 30-dB hearing level. The results suggest that both TEOAEs and DPOAEs are derived largely from similar mechanisms. The differences between the occurrence of the two emissions by audiometric threshold level would suggest that TEOAEs may be preferable for screening purposes, whereas DPOAEs may be more valuable for monitoring cochlear changes clinically. PMID- 8343249 TI - Identifying high-risk patients before head and neck oncologic surgery. AB - Patients from the Comprehensive Cancer Center of the Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, who were undergoing major head and neck oncologic surgery were prospectively studied to determine predictors of postoperative medical complications and wound infection. Of 119 patients studied, 28 (24%) had at least one postoperative medical complication. The strongest predictors of medical complication were poor functional capacity as assessed by the Specific Activity Scale questionnaire and alcohol abuse. Thirteen patients (11%) developed wound infections. The strongest predictors of wound infection were an elevated preoperative platelet count and prolonged surgery. Wound infection was the strongest correlate of prolonged hospital stay. These findings suggest that the Specific Activity Scale questionnaire identifies patients at risk for medical complication, that alcohol abuse should be managed aggressively, and that thrombocytosis identifies patients at risk for wound infection. PMID- 8343250 TI - DNA analysis as a predictor of the outcome of induction chemotherapy in advanced head and neck carcinomas. AB - We investigated whether flow cytometric DNA index and/or ploidy status are predictors of response to chemotherapy and survival. Fifty consecutive patients with previously untreated locally advanced squamous cell carcinomas of the head and neck received induction chemotherapy consisting of three courses of cisplatin (100 mg/m2) and a subsequent 120-hour infusion of fluorouracil (1000 mg/m2 per 24 hours) repeated every 3 weeks. Chemotherapy was followed by radiotherapy to a median target dose of 65 Gy and subsequent surgery for residual tumor. The median observation time was 27 months (range, 24 to 57 months). Flow cytometric DNA analysis was based on formalin-fixed and paraffin-embedded tissue from pretreatment tumor biopsy specimens. Complete response after induction chemotherapy was achieved in only 12% (2/17) of patients with diploid tumors compared with 39% (13/33) of those with nondiploid tumors. Among patients with nondiploid tumors, DNA index was higher for those responding to chemotherapy compared with the nonresponders. Complete response to chemotherapy was apparently a prerequisite for survival in the nondiploid group. Of the patients not responding to chemotherapy but responding to subsequent radiotherapy, survival was better among those with diploid tumors than among those with nondiploid tumors. PMID- 8343251 TI - Cricohyoidopexy in selected infrahyoid epiglottic carcinomas presenting with pathological preepiglottic space invasion. AB - Nineteen patients who presented with infrahyoid epiglottic squamous cell carcinoma with gross pathological preepiglottic space invasion, not amenable to a partial horizontal supraglottic laryngectomy, were offered a supracricoid partial laryngectomy with a cricohyoidopexy technique; this was an attempt to preserve physiological phonation, respiration, and deglutition while achieving the same local control rate as with a total laryngectomy. Preoperative chemotherapy and bilateral jugulocarotid lymph node dissection were performed in all cases. Patients were monitored for at least 5 years or until death. No patients were unavailable for follow-up. The 5-year actuarial survival (Kaplan-Meier method) was 84.2%. Local recurrence, nodal recurrence, and distant metastasis occurred once in our series, while six patients presented with a second primary tumor. We present, analyze, and compare functional results with those of the previously reported series. Our experience with the supracricoid partial laryngectomy with a cricohyoidopexy, in the face of selected infrahyoid epiglottic squamous cell carcinoma invading the preepiglottic space, not amenable to a partial horizontal supraglottic laryngectomy, suggested that a total laryngectomy might be avoided without decreasing the cure rate. PMID- 8343252 TI - Dermatofibrosarcoma protuberans of the head and neck. A report of 16 cases. AB - Dermatofibrosarcoma protuberans of the head and neck is a rare neoplasm. Overall, sarcomas account for less than 1% of all head and neck malignancies. Of 229 patients with sarcomas of the head and neck seen at our institution between 1955 and 1988, 14 (7%) were assigned the diagnosis of dermatofibrosarcoma protuberans after pathologic review. Two additional cases have been seen since 1988, bringing the total to 16. All cases were low-grade lesions. Follow-up ranged from 36 to 198 months, with a median of 114 months. Fifteen patients were managed with surgery alone, and nine (60%) developed local recurrence. Eight were salvaged with further surgery. There were no regional lymph node recurrences or distant metastases. One patient was judged to be a poor surgical candidate and received primary radiation therapy. He died disease free 3 years after treatment. At last follow-up, 15 (94%) of 16 patients were ultimately disease free after salvage treatment. The overall 5-year survival rate was 93% (13/14). We conclude from this series, and from a review of the literature, that wide surgical resection achieving good margins offers excellent probability of cure, and that radiation therapy is a reasonable alternative in patients who have unresectable lesions or who are medically inoperable. PMID- 8343253 TI - The effect of an acute fast on human head and neck carcinoma xenograft. Growth effects on an 'isolated tumor vascular pedicle' in the nude rat. AB - The effects of nutritional state on tumor growth are poorly understood. Most animal studies to date suggest an inhibitory effect of nutritional depletion on tumor growth and a stimulatory effect of nutritional repletion or overfeeding. We have modified an "isolated tumor vascular pedicle" model in the nude rat to study the growth and tumor-specific nutrient utilization of the FaDu cell line of human hypopharyngeal squamous carcinoma. Two weeks after tumor implantation, rats were randomized to either a fed or fasted study group for an additional 7 days. Tumors were significantly larger in the fasted group (0.602 +/- 0.215 g vs 0.362 +/- 0.104 g; P < .02). Whole blood nutrient gradients were determined across the tumor and systemic tissues in both groups. The nutrient gradients across these tissues were significantly different in the fed animals and approached statistical significance in the fasted animals. In addition, there appeared to be a greater utilization of glucose in the fed group (-0.401 +/- 0.904 mmol/L vs 0.298 +/- 0.589 mmol/L), while there was a greater production of lactate in the fasted group (0.798 +/- 0.518 mmol/L vs 0.046 +/- 0.639 mmol/L; P < .1). Flow cytometric analysis revealed no difference in the percentage of cells in any particular stage of the cell cycle between the two groups. These results suggest that the maintenance of adequate body weight may be beneficial not only to the nutrition of the cachectic tumor-bearing host but may also prevent a ketotic state or state of lipolysis that may be preferential to the tumor. PMID- 8343254 TI - Pathologic quiz case 1. Cutaneous angiosarcoma. PMID- 8343255 TI - Validation of personal exposure models for sulfate and aerosol strong acidity. AB - Personal exposure models for sulfates (SO4 =) and aerosol strong acidity (H+) were previously developed using concentration and activity pattern data collected from a personal monitoring study conducted in Uniontown, Pennsylvania, during the summer of 1990. Models were constructed based on time-weighted micro environmental exposures. For SO4 =, the "best-fit" model included a correction factor, while for H+, it included both a correction factor and a neutralization term. In this paper, we present the validation of these models using data collected in a personal monitoring study conducted in State College, Pennsylvania, during the summer of 1991. Indoor and outdoor concentration and activity pattern data collected in this study were used as inputs for the "best fit" models for SO4 = and H+. Predicted personal exposures subsequently were compared to the measured personal exposures from State College to determine their accuracy and precision. Predicted personal exposures for both SO4 = and H+ were in excellent agreement with measured personal exposures from State College. The models explained 91 and 62 percent of the variability in personal SO4 = and H+ exposures, respectively, and were able to estimate personal exposures substantially better than outdoor concentrations alone. Validation results suggest that the models' correction and neutralization factors are not site specific and support the models' future application as a technique to assess the personal acid aerosol exposures of children living in similar rural and semi rural communities. PMID- 8343256 TI - Do dead batteries cause cancer? PMID- 8343257 TI - Salvage intraperitoneal chemotherapy for ovarian cancer: a possible role for mitoxantrone? PMID- 8343258 TI - Mechanisms of carcinogenesis and molecular epidemiology. PMID- 8343259 TI - Carcinoma of the cervical stump: a review of 213 cases. AB - From 1970 to 1987, 213 cases of carcinoma of the cervical stump were accrued in a multi-institutional prospective cooperative study. This group accounted for 5.5% of cervical carcinoma diagnosed during the same period. 13 had in situ carcinoma and 200 had invasive carcinoma (96% squamous cell carcinoma, 4% adenocarcinoma). Radiotherapy alone (external and brachytherapy) was given to 77%, brachytherapy and surgery to 15% and surgery alone to 8%). FIGO stage distribution was: I (31%), IIa (15%), IIb (27%), IIIa (5%), IIIb (17%) and IV (5%). Five-year locoregional control per stage was 100% in Ia, 85% in Ib, 82% in IIa, 71% in IIb, 45% in IIIa, 54% in IIIb and 30% in IV. Corrected 5-year survival per stage was 82% in Ib, 78% in IIa, 73% in IIb, 69% in IIIa, 38% in IIIb and 0% in IV. The diameter of disease in stage II strongly influenced the 5-year locoregional control (81% for tumours of less than 3 cm vs. 68% for tumours more than 3 cm). Lymphangiogram was associated with a 44.5% 5-year locoregional control when positive vs. 74% when non-positive. Brachytherapy was advantageous in obtaining locoregional control in patients receiving external irradiation and brachytherapy: 81.5% vs. 38.5% in patients treated with external radiotherapy alone. Surgery was performed only for in situ carcinoma and for part of stages Ia, Ib and IIa. There is no significant difference in locoregional control at equal stage between radiotherapy alone and treatment schemes including surgery. However, lethal complications were observed in 6% of the patients of the surgical group as compared to 0.6% of the patients treated with radiotherapy alone. Radical radiotherapy seems to provide similar results of locoregional control and survival at equal stages in carcinoma of the cervical stump compared to carcinoma developed on an intact uterus. The rate of severe complications reported with the French-Italian glossary is 13% for G3 and 3% for G4, which is close to the observed rate during the same period in our series of radical radiotherapy to the intact uterus. PMID- 8343260 TI - Long-term adjuvant immunotherapy in stage I high risk malignant melanoma, comparing two BCG preparations versus non-treatment in a randomised multicentre study (EORTC Protocol 18781). AB - The present study reports the results of a multicentre adjuvant trial with BCG (Bacillus Calmette-Guerin) in high risk patients (Breslow thickness > or = 1.5 mm, Clark level > or = III) with malignant melanoma, after surgical removal of their primary tumour. The trial was specifically designed in order to resolve the controversy and to provide some definite answers regarding the value of adjuvant BCG treatment in stage I malignant melanoma. Patients were randomised to either BCG RIV (108 patients) or BCG Pasteur (109 patients) for 3 years or to follow-up only (110 patients). The two vaccines used had greatly divergent properties regarding their mode of preparation, their composition and their immunomodulating activities. Of the 353 randomised patients, 23 were ineligible, 3 refused participation after randomisation and 327 were evaluable for final analysis. Median follow-up time was 6 years (range 0-10 years). The log-rank test comparison showed no statistical difference between the three arms regarding time to progression (P = 0.55) and duration of survival (P = 0.82). Treatment was generally well tolerated, with no major adverse events in either treatment arm. These findings confirm data with different BCG preparations and with stage II melanoma which also demonstrated no benefit regarding patient survival and time to relapse. PMID- 8343261 TI - Phase I-II intraperitoneal mitoxantrone in advanced pretreated ovarian cancer. AB - 36 previously treated patients (25 with anthracyclines) with advanced epithelial ovarian cancer have been treated with intraperitoneal (i.p.) mitoxantrone (M) at increasing doses. The response was evaluated through repeated laparoscopy with multiple biopsies and serial measurement of Ovarian Cancer Antigen 125 (CA 125); 11/36 patients had a complete (6 patients) or partial (5 patients) response. Toxicity (both local and general) was observed starting from 25 mg/m2 of M per cycle. The amount of drug reaching systemic circulation was monitored by measuring M plasma value after i.p. treatment. This study showed wide variations in serum levels obtained after i.p. doses ranging from 23 to 36 mg/m2. The area under the curve (AUC) of mitoxantrone plasma samples, did not correlate with the i.p. administered dose. Conversely, a correlation seems to exist between the plasma AUC and the responder status. Patients who showed clinical responses to i.p. treatment with mitoxantrone had AUCs and plasma peak levels of the drug that were significantly higher than those in non-responders (P = 0.03, Fisher's exact test). PMID- 8343262 TI - Immunoradiometric assay of pro-cathepsin D in breast cancer cytosol: relative prognostic value versus total cathepsin D. AB - In breast cancer cell lines, the maturation of pro-cathepsin D into enzymatically active cathepsin D is altered, leading to its increased secretion. In order to specifically assay pro-cathepsin D (52 kD form) in breast cancer cytosol, we monitored a solid phase sandwich radioimmunoassay using D9H8 and D7E3 monoclonal antibodies raised against human pro-cathepsin D from MCF7 cells. Pro-cathepsin D was assayed in 108 primary breast cancer cytosols in which total cathepsin D was previously found to be correlated with metastasis. Pro-cathepsin D concentrations were found to be correlated with total cathepsin D and with lymph node invasion, and was slightly higher in premenopausal patients. By contrast, Cox multiparametric analysis showed that pro-cathepsin D status had no prognostic value for survival, or metastasis free survival contrary to total cathepsin D status. This first study shows the technical validity of the pro-cathepsin D assay but indicates that it has less value as a prognostic marker than total cathepsin D. This study also shows that the proportion of pro-cathepsin D recovered in vivo (1-6%) is much less than that produced in cell lines and suggests that the secreted pro-enzyme might be activated in the tumour extracellularly or following its reinternalisation. PMID- 8343263 TI - Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters. AB - Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a protein present at high levels in breast cyst fluid, has been measured in 104 breast tumour cytosols by using an immunoenzymatic assay. Concentrations of Zn-alpha 2-gp ranged from 0 to 23.5 micrograms/mg of total soluble protein, with an average value of 2.4 micrograms/mg. There was no significant correlation between Zn-alpha 2-gp and menopausal status, tumour size or lymph node involvement, or between this protein and biochemical parameters such as oestrogen receptor, cathepsin D or pS2 levels. However, there was a significant association between Zn-alpha 2-gp and histological grade of tumours, with higher Zn-alpha 2-gp levels in well differentiated tumours (mean 4.6 micrograms/mg) than in moderately (1.8 micrograms/mg) or poorly (0.9 micrograms/mg) differentiated tumours. On the basis of these results, we propose that Zn-alpha 2-gp may be considered as a biochemical marker of differentiation in breast cancer. PMID- 8343264 TI - The changing importance of prognostic factors in bladder cancer during a long term follow-up. AB - A cohort of 505 patients with a transitional cell bladder cancer were followed up for over 9 years and clinical, histological and morphometric factors were related to survival. Several survival analyses were done by moving the start of the follow-up so that the first analysis started at the time of primary therapy and the last one after 9 years follow-up. T-category, WHO grade, papillary status and the density of tumour infiltrating lymphocytes had independent short-term prognostic value whereas mitotic index and standard deviation (S.D.) of nuclear area were independent long-term predictors up to 7 years after diagnosis. In papillary tumours S.D. of nuclear area and mitotic index were independent long term predictors in contrast to T-category and WHO grade which were both short term prognostic factors. In superficial tumours only mitotic index had independent long-term prognostic value. The results show that the prognostic information from the primary tumour biopsy specimen has long-term prognostic significance in transitional cell bladder cancer. The results particularly emphasize the importance of factors related to cancer cell proliferation as long term predictors. PMID- 8343265 TI - Neuropsychological and neurophysiological assessment of the central effects of interleukin-2 administration. AB - Neuropsychiatric disturbances may occur following interleukin-2 (IL2) administration. We studied the effects of IL2 infusion on cerebral functions in 7 patients with neuropsychological tests and event-related evoked potentials (P300). We observed a failure in the cognitive performances, an increase in latency, and a decrease in amplitude of P300. These effects followed IL2 administration and were reversible. PMID- 8343266 TI - Karyotype in multiple myeloma and plasma cell leukaemia. AB - Between October 1988 and October 1991, 104 patients with multiple myeloma and 6 with plasma cell leukaemia were studied cytogenetically. Abnormal karyotypes were found in bone marrow cells of 33 patients (30%). Most pathological karyotypes were complex with numerous modal and structural anomalies. Numerical anomalies most frequently involved chromosome 11 and structural aberrations occurred most often in chromosomes 1, 11 and 14. The most consistent structural aberration was a 14q+ chromosome (10 patients) resulting from a t(11;14)(q13;q32) in 4 patients and a t(8;14)(q24;q32) in 1 patient. Sequential cytogenetic studies were performed in 15 patients. In 5 of 8 cases with a normal karyotype at diagnosis, chromosomal anomalies were detected when disease progressed. In concomitant cytogenetic/cytological studies it was found that in the majority of patients with normal karyotype the mitoses originated from contaminating normal bone marrow cells. Pathological karyotypes were detected more frequently in pretreated than in untreated patients, in patients with plasma cell leukaemia than in patients with multiple myeloma, in patients with stage III and dense bone marrow infiltration than in patients with stage I. Patients with abnormal karyotype, irrespective if pretreated or not, had a significantly shorter median survival than those with normal karyotype. These findings suggest that karyotype is an independent prognostic factor in multiple myeloma. PMID- 8343267 TI - Ceftriaxone versus latamoxef in febrile neutropenic patients: empirical monotherapy in patients with solid tumours. AB - 121 patients with 132 febrile episodes were randomised to ceftriaxone or latamoxef monotherapy in order to compare antibiotic efficacy in neutropenic patients treated with cytotoxic chemotherapy for solid tumours. In 80 evaluable episodes no significant differences were observed between the two groups with respect to efficacy and fatal failure rates. Of episodes treated with ceftriaxone, 67% showed a favourable clinical response vs. 61% in the latamoxef group. The clinical response rates in episodes with documented bacterial infections were 67 and 56% in the two treatment groups. In 18% of the episodes with documented initial infections the patients died of presumably uncontrolled infection. The convenient once daily dosage schedule combined with fewer severe adverse reactions favours the use of ceftriaxone instead of latamoxef. Although a relative high degree of response was seen, empirical antibiotic monotherapy apparently does not offer a sufficient antibacterial cover in infections in this type of patient with defective host immunity. PMID- 8343268 TI - Oxaliplatin activity against metastatic colorectal cancer. A phase II study of 5 day continuous venous infusion at circadian rhythm modulated rate. AB - Oxaliplatin (L-OHP) is a non-nephrotoxic third generation platinum complex with proven antitumoral activity and minimal haematological toxicity. Circadian scheduling has allowed significant increases in L-OHP dosage and dose intensity and decreases in its toxicities. This phase II trial has tested the antitumour activity of a 5-day circadian schedule of continuous venous infusion of L-OHP against metastatic colorectal cancer. Initial dose was 150 mg/m2/course. An intrapatient dose escalation scheme by 25 mg/m2/course was planned up to 200 mg/m2/course, according to toxicity criteria. The delivery rate of L-OHP was sinusoidally modulated along the 24-h time scale, and was highest at 1600 h. A programmable-in-time ambulatory pump was used, so that all patients could receive their treatment at home. 29 of 30 patients registered were eligible. 25 had failed previous chemotherapy. Three objective responses were observed (response rate: 10%), in patients progressive while on chemotherapy with 5-fluorouracil and folinic acid. Toxicity was moderate. Dose-limiting toxicities were diarrhoea and peripheral sensitive neuropathy. The latter adverse effect appeared to be cumulative. L-OHP, as delivered under this circadian schedule, exhibits clinical antitumour activity against metastatic colorectal cancer. These results, which await further confirmation, support the place of L-OHP in combination regimens including 5-fluorouracil. PMID- 8343269 TI - DNA pattern and dietary habits in patients with breast cancer. AB - An association between dietary fat, micronutrients and breast cancer aetiology and prognosis has been found in studies of experimental animals and in epidemiological studies. The relationship between dietary habits and the nuclear DNA content of breast cancer cells was studied in 82 women aged 50-65 years. A dietary history interview was conducted within 4 months following surgery. Patients having tumours with euploid DNA pattern reported lower mean intake of saturated fatty acids (FA) in absolute terms, lower mean intake of total fat, saturated FA, and monounsaturated FA, in percentage of total energy intake (E%), a higher E% from protein, and a higher intake of vitamin D, and selenium per 10 MJ than did patients having tumours with aneuploid DNA pattern. In the stepwise logistic regression analysis, the multivariate odds ratios (OR) for having a tumour with aneuploid DNA pattern was 1.16 (95% confidence interval, 1.04-1.28) for each 1 g increase in intake of total fat (E%) and 0.95 (95% confidence interval, 0.92-0.99) for each mg increase in selenium intake per 10 MJ. When total fat was substituted with types of fat, the OR for having a tumour with aneuploid DNA pattern was 1.30 (95% confidence interval, 1.07-1.59) for each 1 g increase in intake of saturated FA (E%). These results suggest a correlation between a diet rich in fat and protein and the DNA content of breast cancer cells. PMID- 8343270 TI - Trends in lung cancer mortality in three broad Italian geographical areas between 1969 and 1987. AB - Trends in death certification rates from lung cancer in broad Italian geographical areas (north/centre/south) were analysed over the period 1969-1987. In northern Italy, lung cancer rates in young and middle-aged males reached a peak between the mid and late 1970s, and tended to decline afterwards; only above age 60 was mortality still rising in the 1980s. A similar pattern of age-specific rates was observed in central areas, while in the South rates tended to level off in the early 1980s only below age 55, but were still upwards in subsequent age groups. Consequently, the north/south ratio for the overall age-standard rate increased slightly between the late 1960s and mid 1970s, from 1.68 (corresponding to a world standardised rate of 47.1/100,000 in the north vs. 28.1 in the south) to 1.73, but declined to 1.55 between 1985 and 1987 (for a rate of 69.1/100,000 males in the north vs. 44.6 in south). In the younger age groups a diverging pattern was observed: at ages of 25-34 rates in 1985 and 1987 were apparently higher in the south (1.0 vs. 0.9/100,000 in the north), and in the 35-44 age group the north/south ratio decreased from 1.7 to 1.2 (with rates of 12.9 and 10.7, respectively, in 1985 and 1987). Among females, lung cancer rates increased in all geographical areas and age groups except the youngest (25-34 years). Under the age of 50, the rises were proportionally similar in various geographical areas, thus widening the north/south difference in absolute terms. Above the age of 50, the north/south difference tended to be wider in relative terms too, reaching a factor of 2 in the 65-74 age group. The overall age-standardised north/south ratio for females increased from 1.51 in 1969-1974 (5.6 vs. 3.7/100,000) to 1.87 in 1985-1987 (8.4 vs. 4.5/100,000). These trends reflect changes in smoking habits in subsequent generations of Italian males and females from different areas of the country, and confirm the central role of cigarette smoking in lung cancer rates in various populations, although this does not exclude some influence by other, mainly occupational, lung carcinogens on the substantial differences in lung cancer rates in various Italian geographical areas. PMID- 8343271 TI - Evidence for bimodal distribution of breast carcinoma ER and PgR values quantitated by enzyme immunoassay. AB - Breast carcinoma oestrogen receptor (ER) and progesterone receptor (PgR) values obtained by radioligand binding assays have commonly been observed to have approximate log-normal distributions. We examined the distribution of log transformed receptor values obtained by enzyme immunoassay for 5468 primary breast carcinomas in five Ontario laboratories. In each laboratory, it was found that the frequency histograms for the log transformed receptor values were not unimodal, and generally were suggestive of bimodality. This was not affected by stratification by age or inferred menopausal status (< or = 49, > or = 50 years), and could not be explained by kit characteristics. However, the low point in the distribution varied from 5 to 63 fmol/mg cytosol protein, depending on the receptor, patient age and laboratory. The tendency towards biomodality was more distinct for ER than for PgR. It remains to be determined whether the low points on the frequency histograms have clinical relevance for discriminating between hormone-sensitive and hormone-insensitive tumours. PMID- 8343272 TI - Risk factors for epithelial ovarian cancer in women under age 45. AB - Risk factors for ovarian cancer in young women were investigated using data from a case-control study conducted between 1983 and 1992 in Milan, northern Italy, on 194 women below age 45 with histologically confirmed incident cancers of the ovary and 710 controls admitted to the same network of hospitals for acute non gynecological, nonhormonal and non-neoplastic diseases. An elevated relative risk (RR) of ovarian cancer was found among women reporting 12 or more years of education [RR 1.6, 95% confidence intervals (CI) 1.0-2.03] and belonging to the highest social class (RR 1.8, 95% CI 1.1-3.0). Women whose mothers had had ovarian cancer had a multivariate RR of 2.7 (95% CI 0.7-10.5) compared to those with no family history. Menarche above age 13 and irregular menstrual cycles were significantly protective against ovarian cancer (RR 0.6 for both risk factors). There was a significant inverse relationship with abortions, the RR being 0.6 both for spontaneous and for induced abortions, while protection of parity was not significant. Higher risks of ovarian cancer were observed in women having first or last birth when older than 30 years (RR 2.0 and 2.4, respectively, compared to those delivering under age 25). A significant trend toward an increased risk of ovarian cancer was also observed with decreasing time since last birth. Compared with women whose last birth occurred 10 or more years before diagnosis, the RR was 2.1 (95% CI 1.1-3.9) for those reporting a birth during the last 5 years. The RR for oral contraceptive users was 0.7 (95% CI 0.5-1.0) and the protection increased with duration, with RR of 0.3 (95% CI 0.1-0.7) for 5 or more years of use. This study indicates that, although the incidence of ovarian cancer is higher in older women, recognised risk and protective factors are similar below age 45. An excess risk in the few years after a term delivery is also suggested. PMID- 8343273 TI - Characterisation of muscarinic cholinergic receptors in human ovaries, ovarian tumours and tumour cell lines. AB - Using [3H]quinuclidinyl benzilate (QNB) as radioligand, muscarinic cholinergic receptor sites in isolated plasma membrane fractions from human ovarian tumours, cultured tumour cells, and normal ovarian tissue were characterised. QNB binding to all preparations, except from poorly differentiated tumour, was specific, saturable, and of high affinity. In contrast to normal ovaries, benign tumours, well differentiated adenocarcinoma and OVCAR-3 cells, the poorly differentiated adenocarcinoma and SKOV-3 cells completely lacked specific QNB binding. The muscarinic receptor densities and the Kd values in preparation from ovaries, receptor-positive tumours and OVCAR-3 cells were similar. QNB binding was strongly inhibited by the classical muscarinic receptor antagonist atropine, but poorly by the agonist carbachol. In contrast to atropine, inhibition by pirenzepine and AF-DX 116 was relatively low. These data suggest that muscarinic receptors in ovaries and ovarian tumours are of m3 type. PMID- 8343274 TI - Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours. AB - The cellular expression of O6-alkylguanine-DNA-alkyltransferase (ATase) may be an important factor in determining tumour sensitivity to certain alkylating agents. In a comparative study, we have examined the inter- and intracellular distribution of ATase in tumour biopsies of a series of patients with Hodgkin's disease and ovarian cancer using a rabbit antihuman ATase antiserum. The antibody recognises the ATase protein on western blots of cell-free extracts of a number of ovarian tumours with ATase activities varying from 20 to 420 fmol/mg protein as determined by in vitro assay and there was a linear correlation between ATase activity and the intensity of the band on western blots (r = 0.993). Immunohistochemical staining was seen in all of the ovarian tumours examined and was confined to the nucleus. This is in contrast to the Hodgkin's tissue, where staining was much reduced and present in both nuclei and cytoplasm. The results suggest that in ovarian tumours the general resistance to nitrosourea chemotherapy may be related to the high cellular expression of ATase protein: this is in contrast to the more chemosensitive Hodgkin's disease. This raises the possibility that it might be feasible to predict sensitivity or resistance to these alkylating agents by immunohistochemical staining of tumour or tissue specimens. PMID- 8343275 TI - Continuous intravenous interleukin-2 infusion and subcutaneous interferon-alpha in metastatic renal cell carcinoma. AB - In a phase II trial patients with metastatic renal cell carcinoma (MRCC) received two induction cycles each consisting of 24-h intravenous infusions of interleukin 2 (IL-2) 18 x 10(6) U/m2/day and interferon (IFN) 3 x 10(6) U/m2/day given subcutaneously on days 1-5 and 8-12 of a 2-week cycle. Between cycles 1 and 2 there was a 3-week treatment-free interval. Maintenance therapy consisted of four monthly cycles of IL-2 and IFN. Due to considerable toxicity the trial was prematurely closed after inclusion of 16 of 23 scheduled patients. Three partial responses were observed. Nine events of severe or life-threatening side-effects occurred and 8 patients were transferred to the intensive care unit. The combination of continuous intravenous high-dose infusions of IL-2 and subcutaneously given IFN is moderately effective, but too toxic for routine treatment of MRCC. PMID- 8343276 TI - De novo cisplatinum resistance does not influence cellular radiosensitivity. AB - The intrinsic sensitivity to 4 MeV photons, and 62.5 MeV (p-->Be+) neutrons has been examined in a panel of 11 cultured human cell lines exhibiting a wide spectrum of inherent cisplatinum sensitivity. Irrespective of whether cellular sensitivities to these therapeutic agents were compared at the 10% survival level, relative to the initial portion of the cell survival curves, or to their relative rank order of response, there were no significant correlations between inherent cisplatinum sensitivity and sensitivity to either 4 MeV photon, or 62.5 MeV neutron irradiation. This data raises the possibility that the previously reported decreased radiosensitivity of human tumour cell lines with acquired cisplatinum resistance may be due to the induction of cellular processes which confer resistance to both cisplatinum and ionising radiation, rather than the selection of innately cisplatinum-resistant cells, which are collaterally radioresistant. PMID- 8343277 TI - Vinca alkaloids: anti-vascular effects in a murine tumour. AB - We have investigated the blood flow modifying effects of the vinca alkaloids, vincristine and vinblastine in the murine carcinoma CaNT. Vinblastine at doses of 7.5 or 10 mg/kg induced profound and chronic reductions in tumour blood flow as measured by 86RbCl extraction. Following the maximum tolerated dose of 10 mg/kg, blood flow was reduced to 10% of pretreatment values after 2 h and remained below 20% of pretreatment values 24 h after drug administration. These findings are consistent with the early induction of necrosis by vinblastine and suggest that vascular-mediated cell death may account for a large part of the 11 day growth delay induced by this drug dose. In contrast to the large reductions in tumour blood flow, in skin, kidney, liver and muscle, blood flow reductions did not, at any time examined, exceed 40%. In all the normal tissues studied, blood flow had fully recovered by 6 h after vinblastine administration. Similar results, albeit less pronounced, have been obtained with vincristine at the maximum tolerated dose of 3 mg/kg. The results clearly show that both vinblastine and vincristine can induce, with some selectivity, a dramatic and prolonged reduction in tumour blood flow and that this may contribute to the anti-tumour effects against the CaNT tumour. PMID- 8343278 TI - Lack of correlation between anxiety parameters and oestrogen receptor status in early breast cancer. AB - Correlation between anxiety parameters and oestrogen receptor levels (ER) were investigated in 89 patients with primary breast cancer. Patients were divided into two groups, ER poor (< 0.05 fmol/microgram DNA) and ER rich (> 0.05 fmol/microgram DNA). No differences were found between anxiety levels, determined by a modified Hospital Anxiety and Depression (HAD) scale, in the two groups. This report does not support the findings from other studies, claiming an association between psychological parameters and oestrogen receptor status, which is believed to be a prognostic predictor. PMID- 8343279 TI - CEA-immunoscintigraphy with 99m-technetium correlates with tumour cell differentiation in colorectal cancer. AB - The clinical usefulness of immunoscintigraphy with the monoclonal anti-CEA (carcinoembryonic antigen) antibody BW431/26, directly labelled with 99m Technetium in targeting colorectal carcinomas was investigated in 43 patients. In addition, tumour cell grading and CEA-expression were examined immunohistochemically. Best imaging results were obtained in pelvic tumour lesions (sensitivity 80%). Tumour grading correlated with radioimmunoimaging, well differentiated tumours being detectable at a higher rate (P = 0.09). Immunoscintigraphy preceded the findings of conventional diagnostic methods in 3 patients. In 4 cases immunoscintigraphy was decisive for patients management. Therefore, immunoscintigraphy with 99m-Technetium is valuable in directing patients management if conventional diagnostic methods remain undecisive. PMID- 8343280 TI - Carboplatin in patients with advanced colorectal cancer pretreated with fluoropyrimidines. AB - The activity of carboplatin (CBDCA) was tested in 21 consecutive patients with advanced colorectal cancer that had progressed during fluoropyrimidine therapy. CBDCA was chosen in view of the favourable results obtained in previous phase II studies. We were unable to find any activity of the agent which was given every 21 days at a dose of 400 mg/m2. The main toxicity was haematological. CBDCA is not recommended in pretreated patients with colorectal cancer. PMID- 8343281 TI - Black (air-cured) and blond (flue-cured) tobacco and cancer risk. V: Oral cavity cancer. PMID- 8343282 TI - Carotenoids and cancer: an update with emphasis on human intervention studies. AB - This article gives an overview of the current state of knowledge on the cancer preventive potential of carotenoids. Numerous retrospective and prospective epidemiological studies have shown that a high intake of carotenoid-rich fruits and vegetables is associated with a decreased risk of cancer at a number of common sites. For several other cancer sites, however, the epidemiological evidence is not very consistent. A number of mechanisms for the cancer preventive properties of carotenoids have been proposed. Conversion to retinol, possibly in posthepatic tissues, would allow an effect on cellular differentiation and proliferation, and on cell-to-cell communication. Antioxidant functions could prevent free radical-induced damage to cellular DNA and other macromolecules. Immunomodulatory effects could enhance immune surveillance in tumorigenesis. In addition, non-retinol-mediated effects of carotenoids on metabolism of carcinogens and cell-to-cell communication have been shown. Observational epidemiology cannot resolve whether associations are due to a specific carotenoid, or to an associated factor in fruits and vegetables, whereas interpretation of animal studies is hampered by uncertainties in extrapolation between species, more so because the metabolism of carotenoids in most animals differs notably from that in humans. Human intervention studies on biomarkers related to cancer risk and on cancer incidence are, therefore, necessary. Human intervention studies performed so far suggest that beta-carotene can affect carcinogenesis, though not at all stages and not at all cancer sites. Implications for future human intervention research are discussed. PMID- 8343283 TI - Mechanisms of carcinogenesis: chemical exposure and molecular changes. PMID- 8343284 TI - Report of an international workshop on perspectives on secondary prevention of laryngeal cancer. PMID- 8343285 TI - Phase II study of oral ftorafur and uracil in patients with advanced renal cell carcinoma. PMID- 8343286 TI - A phase II study of etoposide, cisplatin plus methotrexate in patients with advanced refractory breast cancer. PMID- 8343287 TI - Carboplatin hypersensitivity: case reports and review of the literature. PMID- 8343288 TI - Meningeal tumour infiltration in hormone resistant prostate cancer demonstrated with magnetic resonance. PMID- 8343289 TI - A pilot study of vinorelbine on a weekly schedule in recurrent and/or metastatic squamous cell carcinoma of the head and neck. PMID- 8343290 TI - [The endovascular surgery of the cerebral arteriovenous malformations]. PMID- 8343291 TI - [Balloon angioplasty for high grade vasospasm after subarachnoid hemorrhage]. PMID- 8343292 TI - [Intravascular surgery for brain tumors]. PMID- 8343293 TI - [Intravascular surgery for spinal AVM]. PMID- 8343294 TI - [A study on the prediction of long-term prognosis of adulthood epilepsy]. AB - We report results of a study on the relation between the clinical findings 2 years after initiation of the therapy and the long-term prognosis of seizure control, and discuss the possibility of predicting the prognosis in the early stage of therapy. The subjects consisted of 141 patients, observed for 10 to 20 years at Hirosaki University Hospital. Regarding the epilepsy type, the prognosis of temporal lobe epilepsy was unfavorable. In temporal lobe epilepsy, only 21% were in remission (seizure-free for 3 years or more) at the time of the study. Also, the presence of organic brain lesions or neuropsychiatric complications at the early stage of treatment was associated with unfavorable prognosis. We are particularly interested in the possibility of predicting the long-term prognosis from the result of early response to anti-epileptic drug therapy. We found a significant correlation between the early excellent response to drug treatment and the good long-term prognosis. Using discriminant analysis (quantification theory II), we tried to find which factors would influence more to the long-term prognosis. As the result, an importance was found in the following order: (1) epilepsy type, (2) presence or absence of neuropsychiatric complications, (3) age at onset, (4) early response to treatment, (5) presence or absence of organic brain lesions and (6) the interval between the onset and the initiation of drug treatment. Correct identification rate by discriminant analysis was 73%. PMID- 8343295 TI - [A study of plasma atrial natriuretic peptide, antidiuretic hormone and cerebral vasospasms in patients with aneurysmal subarachnoid hemorrhage]. AB - The relationship between plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) both of which show high values after subarachnoid hemorrhage and cerebral vasospasm was studied. The subjects were 23 patients who were admitted because of aneurysmal subarachnoid hemorrhage during three years from March, 1989 to March, 1992 and in whom plasma ANP and ADH levels could be determined over time. Cerebral vasospasm was evaluated by the finding of cerebral angiography, clinical symptoms, and presence or not of low density areas on CT. Hyponatremia was defined as the serum sodium level of 130 mEq/l or less for two days or more. Angiographical vasospasm was found in 17 patients (85%), symptomatic vasospasm in 15 patients (65.2%), low density areas on CT in 9 patients (40.9%) and hyponatremia in 8 patients (34.8%). Symptomatic vasospasm was noted in 7 of the 8 patients (87.5%) with hyponatremia, low density areas on CT in 4 patients (50%), the detection rate being high. The plasma ANP and ADH levels were 76.7 +/- 32.1 pg/ml and 2.2 +/- 0.7 pg/ml respectively in the patients with symptomatic vasospasm against 38.3 +/- 21.3 pg/ml and 2.4 +/- 0.6 pg/ml respectively without symptomatic vasospasm, the plasma ANP level being significantly high in the patients with symptomatic vasospasm (p < 0.01). The plasma ANP and ADH were 71.2 +/- 33.8 pg/ml and 2.0 +/- 1.1 pg/ml respectively in the patients with low density areas on CT against 51.2 +/- 31.3 pg/ml and 1.8 +/- 0.5 pg/ml respectively without low density areas on CT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343296 TI - [Evaluation of surgical treatment for chronic subdural hematoma in extremely aged (over 80 years old) patients]. AB - A consecutive series of 76 aged (over 80 years old; 50 male, 26 female) patients with chronic subdural hematoma (CSDH) was studied. They were analyzed about interval form trauma, preoperative grade according to Bender scale, coexisting disease, volume and location of hematoma, surgical procedures, postoperative outcome and complications. Sixty-six% of patients had a history of trauma. Clinical findings at the time of admission were graded according to Bender scale. The majority of patients belonged to grade 2 (41 cases) and grade 3 (23 cases) followed by grade 1 (8 cases) and grade 4 (4 cases). The volume of CSDH was classified into three group; under 79 ml (21 cases), between 80 and 119 ml (28 cases), over 120 ml (27 cases). Almost all of patients were operated by burr hole, irrigation with drainage or Ommaya's reservoir. Six cases needed reoperation. Six cases suffered from infections. Sixty-eight (89%) patients improved at the time of discharge. Surgical procedure is the best choice for CSDH even in extremely aged patients. PMID- 8343297 TI - [A case of atypical senile dementia of Alzheimer type]. AB - We describe the autopsy finding in a male patient with senile dementia of unusually prolonged total duration, who had exhibited atypical neuropathologic findings. During clinical course, memory disturbance had been more prominent than deterioration of other cognitive functions. Neuropathologic examination revealed neurofibrillary changes which were prominent in the hippocampal region and scattered in the amygdala and in the predilection sites of the hypothalamus and brain stem. This distributional pattern was that in Alzheimer-type dementia. The most characteristic finding was scanty senile plaques, which were scattered predominantly in the basal and medial portion of the frontal lobe. Although the clinical course and pathological findings of this case were in slight degree and deviated from those in usual senile dementia, it is thought that the entity in this case was dementia of the Alzheimer-type. PMID- 8343298 TI - [A case report of Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral thalamomesencephalic lesion]. AB - We report a rare case showing Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral lesion of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), which is regarded as the supranuclear control center of vertical gaze. To date, no literature concerning Weber's syndrome associated with the ipsilateral riMLF lesion was documented. The patient was a 53-year-old female, who suddenly developed unconsciousness and left sided weakness. Neurological findings on admission revealed right third nerve palsy, severe supranuclear vertical gaze palsy, almost complete convergence palsy, left hemiparesis and hyperreflexia with positive Babinski's sign on the left side. There was no sign of pupillary disturbance or no abnormality of the horizontal movements of the left eye. The vestibulo-ocular reflex of the left eye was preserved. There was no sensory disturbance. Cranial MRI had the advantages in demonstrating unilateral ischemic lesions at the cerebral peduncle and the thalamomesencephalic junction involving the unilateral riMLF on the right side. Recent reports have demonstrated that supranuclear vertical gaze palsy is caused by the unilateral riMLF lesion. We confirm that the unilateral riMLF lesion causes supranuclear vertical gaze palsy in our case and that cranial MRI has the advantages in demonstrating the specific lesion. PMID- 8343299 TI - [A case of selective short-term memory disturbance due to a glioma in the left temporo-parietal lobe]. AB - We report a patient with selective short-term memory disturbance caused by a glioma in the left temporal-parietal lobe. The patient was a 40-year-old right handed housewife who complained of difficulty in memorizing series of numbers. She was working as a car dealer. She was well until 6 months prior to the present admission when she noted a difficulty in memorizing series of numbers such when telephone numbers and car registration numbers. She had to write them down as her customers told them to her. On admission, she was alert and oriented to all spheres. She was mentally sound without dementia. She did not show aphasia, apraxia, or agnosia, except for brief periods of seizures in which she became unable to speech. Neuropsychological examination revealed that she had difficulty in repeating and dictating series of numbers and meaningless kana words. However, she could easily pick up the correct series of numbers or kana words among multiple choices presented visually. Thus it was clear that her problem was not the disturbance of auditory input nor expression, but a selective impairment of short-term memory. She could memorize the same stimuli when visually presented. Therefore, her problem was thought to be a disturbance of auditory short-term memory of meaningless words. After resection of her tumor, she developed transient amnesic aphasia, which improved a year later. She was examined again in her memory function. In the task of visual stimuli, we presented her a card in which a series of numbers or a nonsense syllable was written for 5 seconds and asked her to remember them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343300 TI - [Thalamic infarction in young adult caused by embolism from an unruptured aneurysm of the posterior cerebral artery--a case report]. AB - A 21-year-old man presented with sudden weakness and dysesthesia of his right limbs. Computerized tomography (CT) scan showed a low density area in the posterolateral part of the left thalamus. Right vertebral angiography revealed a small aneurysm at the P2 segment of the posterior cerebral artery. Magnetic resonance imaging (MRI) demonstrated intra-aneurysmal clot and signal void in the residual lumen. There were no other lesion and no predisposing risk factors that produced cerebral ischemia. It was thought that the aneurysm was the source of emboli resulting in thalamic infarction. The patient underwent a left subtemporal craniotomy, and the aneurysm was clipped. Following surgery, there has been no recurrence of ischemic attacks. The diagnosis and the therapy were discussed, with reference to the literature. PMID- 8343301 TI - [A large vertebrobasilar junction aneurysm grown at the proximal end of basilar artery fenestration--usefulness of balloon occlusion test with 99mTc-HMPAO SPECT under induced hypotension and consideration in therapeutic strategies]. AB - A 48-year-old lady suffered a transient loss of consciousness. CT and MRI revealed a large vascular lesion compressing the left lower pons. Angiography revealed a large aneurysm at vertebro-basilar junction, dome of which projected anteriorly and left to midline. Her previous vertebral angiogram taken 10 years ago when she suffered a subarachnoid hemorrhage from the left MCA aneurysm, had showed a fenestration of lower basilar artery without apparent aneurysm. Bilateral super-selective vertebral angiograms revealed that the aneurysm arose at the proximal end of the fenestration, and vertebrobasilar junction was incorporated into the aneurysm indicating broad neck aneurysm. The left posterior communicating artery was well developed. Balloon test occlusion (BTO) of bilateral vertebral artery was performed under normotension and induced hypotension. 99mHM-PAO SPECT was used to examine cerebral blood flow (CBF) during hypotensive BTO. The patient tolerated the test and CBF imaging showed insignificant sight decrease in bilateral cerebellar hemispheres. Exploration of the aneurysm was carried out by the right far lateral suboccipital approach. Bilateral vertebral arteries and the right segment of the basilar artery fenestration were identified. Neck clipping of the aneurysm with reconstruction of the parent vessels were tried with fenestrate clip. However, narrow operative field and large dome of the aneurysm made it hard to identify the left segment of the fenestration. Neck clipping was given up and clipping of bilateral vertebral arteries were performed distal to posterior inferior cerebellar artery with three body clippings. The patient showed moderate postoperative left lower nerve palsy, which was gradually improved in several weeks. Follow-up angiography revealed no opacification of the aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343302 TI - Self-scheduling guidelines. Pediatric unit. Mercy Hospital and Medical Center, San Diego, California. PMID- 8343304 TI - Nurse executives share their first class ideas. Outcome-based resource management. PMID- 8343303 TI - When patient classification systems fail. PMID- 8343305 TI - ANA blueprint for transition: the matrix plan for nursing initiatives in managed care. PMID- 8343306 TI - Partnering with your human resource department. PMID- 8343307 TI - Self-scheduling: a practical application of shared governance. PMID- 8343308 TI - Learned optimism. PMID- 8343309 TI - Insulin and atherosclerosis: villain, accomplice, or innocent bystander? PMID- 8343310 TI - Oxidised low density lipoproteins and atherogenesis. PMID- 8343311 TI - Radiation induced coronary heart disease. PMID- 8343312 TI - Radiotherapy, left-sided breast cancer, and ischaemic heart disease. PMID- 8343313 TI - Non-invasive diagnosis of arterial patency after thrombolytic treatment and its relation to prognosis. AB - OBJECTIVE: To validate a simple noninvasive method with serial creatine kinase measurements for diagnosis of early patency of the infarct related artery after thrombolytic treatment with streptokinase. To investigate the relation between early patency of the infarct related artery and prognosis. DESIGN: Patients under 76 years of age and seen within six hours of the start of prolonged chest pain and ST segment elevation were treated with streptokinase (1.5 x 10(6) U) intravenously over 30-60 minutes. Blood for measurement of total creatine kinase activity was taken at baseline and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours after starting treatment. The rise in enzyme activity at each time from baseline was expressed as a proportion of the total rise from baseline to peak. PATIENTS: Patients studied were in the following groups: (a) Sixty patients took part in a validation study with angiographic determination of patency of the infarct related coronary artery at 2.6 (0.3) hours (mean (SD)) after starting streptokinase. (b) A further 258 patients did not have early arteriography, but data were added to those from the 60 validation patients to find the relation between enzymatically determined early patency of the infarct related artery and 30 day mortality. (c) A further subset of 232 patients with first infarctions (including patients from groups (a) and (b) had angiocardiography at three weeks after infarction, and data were used to investigate the relation between early patency of the infarct related artery and left ventricular function. MAIN OUTCOME MEASURES: Normalised rate of rise of creatine kinase activity at three hours after starting streptokinase in relation to angiographic patency of the infarct related coronary artery at 2.5 hours; 30 day cardiac mortality; and left ventricular function at three weeks in survivors of first infarction. RESULTS: In the validation study, a rise in three hour creatine kinase activity of > 20% of peak occurred in 34/37 patients with initially patent infarct related coronary arteries (sensitivity 92%), and a rise to < 20% of peak occurred in 21/23 patients with initially occluded arteries (specificity 91%). In the prognostic study, 30 day mortality was 2.1% in the 191 patients with three hour creatine kinase > 20% of peak and 8.7% in the 127 patients with three hour creatine kinase < 20% of peak (p < 0.01). Angiocardiography in three week survivors of anterior infarction (n = 95) showed better left ventricular function when three hour creatine kinase was > or = 20% than when it was < 20% of peak (mean (SEM) end systolic volume 71 (5) v 96 (9) ml, p < 0.02; ejection fraction 56% (2%) v 51% (2%), NS). CONCLUSION: Non-invasive determination of early patency of the infarct related artery by the normalised rate of rise of creatine kinase activity at three hours seems to be reliable, and may be prognostically important and of value for use in clinical trials. PMID- 8343314 TI - Aspirin does not improve early arterial patency after streptokinase treatment for acute myocardial infarction. AB - OBJECTIVE: To investigate the hypothesis that the magnitude of the life saving effect of aspirin in the second international study of infarct survival (ISIS-2) trial cannot be explained solely by prevention of late reocclusion of the infarct related artery. The aim of this study was to discover whether or not aspirin in combination with streptokinase had an adjuvant thrombolytic effect. DESIGN: Aspirin (150 mg) or placebo was given at the start of streptokinase infusion to 200 patients seen within six hours of the start of prolonged ischaemic cardiac pain and ST segment elevation. All patients received active aspirin at three hours. Patency of the infarct related artery was assessed non-invasively by the normalised rise of creatine kinase activity at three hours after starting streptokinase in these 200 patients and in a further 52 patients who had already taken aspirin within one week of the start of infarction. MAIN OUTCOME MEASURE: Rise in creatine kinase activity from baseline to > or = 20% or < 20% of the peak rise of activity in blood taken at three hours after starting infusion of streptokinase. This correlates with patency or occlusion of the infarct related coronary artery at about 2.5 hours after starting streptokinase. RESULTS: Assessed in this way, patency of the infarct related artery was 60% in patients given aspirin, 63% in those given placebo, and 62% in patients who had already taken aspirin within one week of infarction. CONCLUSION: The magnitude of the life saving effect of aspirin remains unexplained. Further investigation is needed into the mechanism of action of antiplatelet treatment in relation to thrombolytic treatment. PMID- 8343315 TI - Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. AB - OBJECTIVE: To define the clinical and angiographic features and the therapeutic problems in patients with coronary artery disease after therapeutic irradiation of the chest. DESIGN: An observational retrospective study. SETTING: The cardiac catheterisation laboratory, university medical school. PATIENTS: 15 subjects (8 men and 7 women, aged 25-56 years, mean 44) examined in the cardiac catheterisation laboratory, who had significant coronary artery disease years after having radiation treatment to the chest and anterior mediastinum. In the early stages of the study angiography was performed because of typical symptoms of ischaemic heart disease. Later on it was performed because of a high index of suspicion in people with signs of extensive radiation heart damage. MAIN OUTCOME MEASURES: Clinical and electrocardiographic evidence of ischaemic heart disease; echocardiographic signs of pericardial, myocardial or valvar involvement; angiographic evidence of coronary arterial stenosis, with special attention to the ostia; haemodynamic and angiographic signs of pericardial, myocardial, and valvar disease. Survival and symptomatic and functional status were ascertained after medical or surgical treatment. RESULTS: The patients were relatively young and had no risk factors. Seven patients had no signs or symptoms of ischaemic heart disease. Ten patients had ostial stenosis, which was associated with extensive involvement of other cardiac structures in nine of them. Seven required surgical treatment for coronary artery disease. Two died, one at surgery and the other one six months later. Five patients had complications associated with irradiation. CONCLUSIONS: Coronary arterial disease can be reasonably ascribed to the effects of chest irradiation when the patients are young and free from risk factors, especially if the obstructions are ostial and there is important damage to other cardiac structures. In patients with damage to other cardiac structures angina and infarction are often absent and coronary angiography seems to be mandatory. Patients often require surgical treatment and postoperative complications are common. PMID- 8343316 TI - Early changes in left ventricular subendocardial function after successful coronary angioplasty. AB - OBJECTIVE: To study the early effects of coronary angioplasty on resting left ventricular long axis function, reflecting that of the subendocardium. DESIGN: Prospective echocardiographic and Doppler examination of patients with coronary artery disease, before and after single vessel coronary angioplasty. SETTING: A tertiary referral centre for cardiac diseases with facilities for invasive and non-invasive investigation. PATIENTS: 23 patients with significant left coronary disease being considered for coronary angioplasty. RESULTS: Before angioplasty the mean (SD) isovolumic relaxation time was longer than normal (75(19) ms v 55 (10), p < 0.001) with a significant increase in transverse dimension change before mitral valve opening, and peak rate of early diastolic thinning (8(3) v 10.4 (2.6) cm/s (p < 0.001)) was reduced. Long axis motion was frequently abnormal. The interval from the onset of the Q wave to the onset of shortening was prolonged (118 (30) ms v 90 (19) at the left site and 115 (26) ms v 81 (9) at the septal site, p < 0.001) and the onset of early diastolic rapid lengthening delayed with respect to the aortic valve closure sound (A2) by 85 (34) ms v 58 (11) at the left site and 88 (33) ms v 60 (9) at the septal site (p < 0.001). Although overall amplitude was reduced at the septal site only (1.23 (0.3) cm v 1.5 (0.4), p < 0.05), the extent (0.8 (0.2) cm v 1.04 (0.3) at the left site and 0.66 (0.2) cm v 0.9 (0.3) at the septal site, p < 0.001) and peak rate (6.2 (2) cm/s v 10 (2.5) at the left site and 5.4 (2.3) cm/s v 8.5 (2) at the septal site, p < 001) of early diastolic lengthening were both much lower than normal. The E/A ratio on transmitral Doppler was modestly reduced (1.0 (0.7) v 1.4 (0.4), p < 0.05). After angioplasty: isovolumic relaxation time shortened to 64 (18) ms (p < 0.001) and left ventricular incoordination regressed. Long axis shortening with respect to Q (98 (32) ms v 118 (30) at the left site and 94 (23) ms v 115 (26) at the septal site, p < 0.01) and that of lengthening with respect to A2 both normalised. Early diastolic peak lengthening rate increased (7.5 (2.1) cm/s v 6.2 (2) at the left site, and 6.3 (2.4) cm/s v 5.4 (2.3) at the septal site, p < 0.001). The early diastolic peak thinning rate of the posterior wall significantly increased (10 (3.5) cm/s v 8 (3), p < 0.005) as did mitral E/A ratio 1.2 (0.7) v 1.0 (0.7), p < 0.05). CONCLUSION: Long axis motion, representing the function of longitudinally arranged subendocardial fibres, is consistently abnormal in the resting state in coronary artery disease. These systolic and diastolic abnormalities return towards normal after successful angioplasty, suggesting that they are the direct effect of coronary artery stenosis. PMID- 8343317 TI - Increased response of diastolic blood pressure to exercise in patients with coronary artery disease: an index of latent ventricular dysfunction? AB - OBJECTIVE: To determine whether an abnormal response of diastolic blood pressure during treadmill exercise stress testing correlated with the number of obstructed vessels and with left ventricular systolic function in patients with coronary artery disease. DESIGN: Diastolic blood pressure was measured invasively during exercise stress testing and coronary angiograms and left ventriculograms were obtained at rest in patients with coronary artery disease. The abnormal (> or = 15 mm Hg) diastolic blood pressure response was compared with the number of obstructed coronary arteries and with left ventricular systolic function. SETTING: Two tertiary referral centres. PATIENTS: 50 consecutive patients (mean age 57 years) with coronary artery disease. MAIN OUTCOME MEASURES: The increase in diastolic blood pressure during exercise and its correlation with the appearance and disappearance of ST segment deviation, resting left ventricular systolic function, and the number of obstructed coronary arteries. RESULTS: Group 1: 10 (20%) patients (three with one, four with two, and three with three vessel coronary artery disease) (mean (SD) age 54.7 (12) years) had an abnormal diastolic blood pressure response that appeared 1.2 (0.3) min before ST segment deviation and became normal 0.9 (0.3) min after the ST segment returned to normal. Group 2: 40 (80%) patients (12 with one, 16 with two, and 12 with three vessel coronary arteries disease) (aged 56.8 (8.2) years) had a normal diastolic blood pressure response to stress testing. The ejection fraction (46.3 (5)%) and cardiac index (2.6 (0.1) 1/min/m2) in group 1 were less than in group 2 (61.6 (4.2)% and 3.8 (0.3) 1/min/m2 respectively, p < or = 0.001). The end systolic volume was greater in group 1 than in group 2: 38.7 (0.7 ml/m2 v 28.2 (2.1) ml/m2, p < or = 0.001. CONCLUSION: In patients with coronary artery disease an abnormal increase in diastolic blood pressure during exercise stress testing correlated well with left ventricular systolic function at rest but not with the number of obstructed coronary arteries. The abnormal response of diastolic blood pressure probably reflects deterioration of myocardial function. PMID- 8343319 TI - Maternal mortality from heart disease in pregnancy. PMID- 8343318 TI - Effect of hyperventilation and mental stress on coronary blood flow in syndrome X. AB - OBJECTIVES: To assess the effect of hyperventilation and mental stress on coronary blood flow and symptom production in patients with syndrome X. DESIGN: A prospective study. Hyperventilation and mental stress tests were performed on the ward and were repeated in the cardiac catheter laboratory where coronary blood flow velocity was also measured with an intracoronary Doppler catheter in the left anterior descending coronary artery. Oesophageal manometry studies were also performed. PATIENTS: 29 patients with syndrome X (typical anginal chest pain, a positive exercise test, and normal coronary angiogram). SETTING: A regional cardiothoracic centre. RESULTS: Hyperventilation produced typical chest pain in 16 patients on the ward. 13 patients experienced their typical chest pain with mental stress test 5. Ten patients experienced chest pain with both hyperventilation and mental stress tests. This pattern was reproduced exactly when the tests were repeated in the cardiac catheter laboratory. Hyperventilation produced a significant increase in the rate-pressure product during ward and laboratory testing. There was, however, no significant change in the rate pressure product on mental stress tests. The mean (SEM) coronary flow velocity decreased significantly on hyperventilation in the catheter laboratory from 10.0 (0.92) cm/s to 5.9 (0.72) cm/s (p < 0.001). There was also a significant reduction in the mean (SEM) coronary blood flow velocity on mental stress tests from 9.8 (0.86) cm/s to 7.4 (0.6) cm/s (p < 0.001). This reduction in flow velocity occurred in the absence of any changes in diameter of the left anterior descending artery. Further analysis showed that the coronary flow velocity was reduced significantly in only that group of patients in which hyperventilation and mental stress provoked chest pain. There was a significant increase in the arterial concentrations of noradrenaline on both hyperventilation and mental stress testing. Oesophageal manometry showed abnormalities in 17% of patients. CONCLUSIONS: Both hyperventilation and mental stress can produce chest pain in patients with syndrome X and this is associated with a reduction in coronary blood flow velocity. The results of this study suggests that this reduction in coronary flow occurs as a result of increased microvascular resistance. PMID- 8343320 TI - Autonomic function in hypertrophic cardiomyopathy. AB - BACKGROUND: Autonomic dysfunction has been found to be a powerful predictor of arrhythmic events and sudden death after myocardial infarction. Hypertrophic cardiomyopathy carries a risk of sudden death and this risk is increased by the occurrence of syncope. OBJECTIVES: To determine if autonomic dysfunction occurs in patients with hypertrophic cardiomyopathy and if it is associated with the occurrence of syncope. PATIENTS AND METHODS: Autonomic function was measured in 30 patients with hypertrophic cardiomyopathy, 15 with and 15 without a history of syncope, and in 28 healthy volunteers. RESULTS: Tests of parasympathetic activity showed that the mean (SD) variation in heart rate during deep breathing was reduced in patients compared with controls, 17 (9) v 22 (9) beats/min, p = 0.03, the Valsalva ratio was also reduced in patients, 1.52 (0.33) v 1.70 (0.36), p = 0.05 but the immediate heart rate response to standing, the 30:15 ratio, was similar in both groups. Tests of sympathetic activity--namely the diastolic blood pressure response to sustained handgrip and the change in systolic blood pressure on standing--did not differ between patients and controls. There was no significant difference in autonomic function between patients with and without a history of syncope. A secondary predetermined analysis showed that the degree of impairment in variation of heart rate with breathing was correlated with the severity of left ventricular hypertrophy, r = 0.39, p = 0.03. CONCLUSIONS: Patients with hypertrophic cardiomyopathy have a selective impairment of variability of heart rate with deep breathing and the Valsalva manoeuvre indicating decreased cardiac parasympathetic activity. The data suggest that the afferent limb of these reflexes is impaired and that the severity of impairment is related to the degree of left ventricular hypertrophy. PMID- 8343321 TI - A comparison of transoesophageal atrial pacing and direct current cardioversion for the termination of atrial flutter: a prospective, randomised clinical trial. AB - OBJECTIVE: To compare the safety and efficacy of transoesophageal atrial pacing (TAP) with an easily swallowed pill electrode and direct current cardioversion (DCC) in patients with atrial flutter that was refractory to appropriate medical treatment. DESIGN: Prospective, randomised clinical trial. SETTING: Community based United States naval hospital. SUBJECTS: Twenty one consecutive patients with refractory atrial flutter selected consecutively from the inpatient cardiology consultation service. All patients were haemodynamically stable and medical treatment with a class IA or IC antiarrhythmic agent had failed. Eleven patients were treated with TAP and 10 patients were treated with DCC. INTERVENTIONS: Digoxin was given to all patients to control the ventricular rate to < 100/minute. MAIN OUTCOME MEASURE: Conversion to normal sinus rhythm and arrhythmias after cardioversion. RESULTS: Conversion to normal sinus rhythm was similar in both groups (TAP 8/11, DCC 9/10, p = 0.31). Arrhythmias after cardioversion including third degree heart block and non-sustained ventricular tachycardia were more frequent in the DCC group (TAP 0/11, DCC 6/10, p = 0.02). CONCLUSION: Transoesophageal atrial pacing with an easily swallowed pill electrode is safe, well tolerated, and is as efficacious as DCC for refractory atrial flutter. PMID- 8343322 TI - Pulmonary artery pressure and the acute chest syndrome in homozygous sickle cell disease. AB - OBJECTIVE: To investigate whether attacks of acute chest syndrome affected pulmonary artery pressure in patients homozygous for sickle cell disease. MAIN OUTCOME MEASURES: Pulmonary artery pressure, assessed by non-invasive echocardiographic techniques. PATIENTS: 20 patients with homozygous sickle cell disease with a history of at least six episodes of acute chest syndrome and in 20 age, sex, and height matched controls with homozygous sickle cell disease without a history of acute chest syndrome. RESULTS: There was no difference in any of the echocardiographic or Doppler indices between these two groups. CONCLUSIONS: Repeated attacks of acute chest syndrome by the mean age of 12 (range eight to 16) years have not had a discernible effect upon pulmonary artery pressure. PMID- 8343323 TI - Employment and insurance for young adults with congenital heart disease. AB - OBJECTIVE: To determine the life and health insurability and employability of young adults with congenital heart disease. DESIGN: Questionnaire study. SETTING: Cardiac department of a tertiary referral hospital for children. PATIENTS: Young adults 18-30 years old with a variety of congenital heart defects, both simple and complex, including postoperative patients. MAIN OUTCOME MEASURES: Availability of insurance at normal or high rates, with or without special conditions or exclusions. Prospects for employment. RESULTS: Questionnaires were sent to eight large life insurance companies, five health insurance companies and, 15 employers, and 26 replies were received (93%). The consensus for life insurability was that young adults with mitral valve prolapse without regurgitation, postoperative ductus arteriosus, and aortic coarctation were insurable at standard rates. Those with any of the other heart defects listed were either insurable at high rates, or in the case of many lesions, not insurable at all. The consensus for health insurance was that insurance was available, but with complete exclusion of benefit for the cardiac disorder. Employment prospects were good for those with simple defects, but poorer for those with complex lesions. CONCLUSIONS: Prospects for insurance and employment for young adults with complex congenital heart lesions are poor. Inconsistencies found in insurance and job policies may be due to lack of appropriate guidelines for the outcome of young adults with corrected and uncorrected congenital heart disease. PMID- 8343324 TI - Use of a second transcatheter Rashkind arterial duct occluder for persistent flow after implantation of the first device: indications and results. AB - OBJECTIVE: To assess the efficacy, feasibility, and most appropriate timing of the implantation of a second Rashkind arterial duct occluder because of persistent flow after the first device. DESIGN: A prospective serial Doppler study of patients after the insertion of a Rashkind arterial duct occluder including a subgroup in whom a second device was implanted. SETTING: A tertiary referral centre for congenital heart disease. PATIENTS: 144 patients aged 7 months to 67 years (median 3.38 years) who underwent transcatheter occlusion of patent arterial duct, 20 of whom had attempted implantation of a second device. INTERVENTIONS: Implantation of a second device alongside the first was attempted in 20 of the patients with persistent residual flow. MAIN OUTCOME MEASURES: Successful implantation of a second device, the incidence of complications, and the achievement of complete occlusion on follow up Doppler echocardiography. The time to complete occlusion in the whole group and factors predictive of persistent leak were also analysed. RESULTS: Second devices were successfully implanted in 19 of 20 first attempts and in the remaining patient at the second attempt. Complete occlusion was found in 19 patients at a mean follow up of eight months. The complications included fracture of a guidewire requiring femoral arteriotomy for its removal in one patient and embolisation of a device in another. With a single device, persistence of residual flow six months after implantation and malposition of the device on the aortogram after implantation were predictive of continuing residual patency. CONCLUSIONS: Implantation of a second device is safe, feasible, and effective and should be considered when residual flow persists beyond six months, or if malposition of the first device causes complications such as haemolysis. PMID- 8343326 TI - Increased expression of interleukin 6 mRNA in cardiac myxomas. AB - In three patients with cardiac myxoma increased expression of interleukin 6 (IL 6) mRNA was found in the myxoma tissue by polymerase chain reaction (PCR) and in situ hybridisation. These cases suggest that IL-6 is overproduced in the myxoma tissue and secreted into the systemic circulatory system. This might contribute to the systemic inflammatory or autoimmune manifestations seen in cardiac myxoma. This study also showed the usefulness of PCR and in situ hybridisation for the evaluation of mRNA expression in small samples of tissue. PMID- 8343325 TI - Technique of percutaneous laser-assisted valve dilatation for valvar atresia in congenital heart disease. AB - OBJECTIVE: To investigate the efficacy and safety of transcatheter laser-assisted valve dilatation for atretic valves in children with congenital heart disease. DESIGN: Prospective clinical study. SETTING: Supraregional paediatric cardiology centre. SUBJECTS: Eleven children (aged 1 day-11 years; weight 2.1-35.7 kg) with atresia of pulmonary (10) or tricuspid (one) valve underwent attempted laser assisted valve dilatation as part of the staged treatment of their cyanotic heart disease. INTERVENTION: After delineating the atretic valve by angiography and/or echocardiography a 0.018 inch "hot tip" laser wire was used to perforate the atretic valve. Subsequently the valve was dilated with conventional balloon dilatation catheters up to the valve annulus diameter. RESULTS: Laser-assisted valve dilatation was successfully accomplished in nine children. In two neonates with pulmonary valve atresia, intact ventricular septum, and coexistent infundibular atresia the procedure resulted in cardiac tamponade: one died immediately and one later at surgery. During a follow up of 1-17 months (mean 11) two infants with pulmonary valve atresia and intact ventricular septum died (one with congestive cardiac failure). The remainder are either well palliated and do not require further procedures (three), or are awaiting further transcatheter or surgical procedures because of associated defects (four). CONCLUSIONS: Laser assisted valve dilatation is a promising adjunct to surgery in this high risk group of patients. It may avoid surgery in some patients, and may reduce the number of surgical procedures in those requiring staged operations. PMID- 8343328 TI - Coronary heart disease in Indians, Pakistanis, and Bangladeshis: aetiology and possible prevention. PMID- 8343327 TI - A patient in whom self-terminating ventricular fibrillation was a manifestation of myocardial reperfusion. AB - Self-terminating ventricular fibrillation was recorded in a 47 year old woman without coronary artery or other structural heart disease. Reperfusion was thought to be responsible for the ventricular fibrillation because the arrhythmia started while the ST segment was returning to the baseline during an episode of silent ischaemia that was probably caused by coronary spasm. This case shows that potentially lethal arrhythmias can arise during reperfusion and that ventricular fibrillation during reperfusion may be self-terminating. PMID- 8343329 TI - Early and late arrhythmias after the Fontan operation: predisposing factors and clinical consequences. PMID- 8343330 TI - Bedside APTT and PT monitoring. PMID- 8343331 TI - Respiratory depression after extradural fentanyl. PMID- 8343332 TI - Neuromuscular block and insertion of the laryngeal mask airway. PMID- 8343333 TI - Preoperative fasting guidelines for cataract surgery under regional anaesthesia. PMID- 8343334 TI - Anesthesia for nasotracheal intubation in dentistry. PMID- 8343335 TI - Thrombelastography in the management of cardiopulmonary bypass for a patient with reduced prothrombin conversion because of a rare familial haemostatic defect. PMID- 8343336 TI - Arterial pressure measurement in pregnancy. PMID- 8343338 TI - Long-term backache after extradural or general anaesthesia for manual removal of placenta. PMID- 8343337 TI - Thoracic electrical bioimpedance or thermodilution for measurement of cardiac index. PMID- 8343339 TI - Post-spinal headaches in parturient women. PMID- 8343340 TI - The reinforced laryngeal mask airway in paediatric radiotherapy. PMID- 8343341 TI - Use of the laryngeal mask airway in children with laryngotracheal pathology. PMID- 8343342 TI - Adrenoceptors as models for G protein-coupled receptors: structure, function and regulation. PMID- 8343343 TI - Influence of the route of administration on the pharmacokinetics of pirprofen enantiomers in the rat. AB - The pharmacokinetics of the enantiomers of the non-steroidal anti-inflammatory drug pirprofen were studied in male Sprague-Dawley rats after oral and intravenous (iv) doses of the racemate. No significant differences were detected between the enantiomers after oral or iv dosing in t1/2, Vd, or sigma Xu. However, the R:S area under the plasma concentration (AUC) ratio after oral doses (0.92 +/- 0.13) was slightly but significantly lower than after matching iv doses (1.05 +/- 0.036). The absolute bioavailability of the active S-enantiomer (78.5%) after oral doses was higher than the inactive R-enantiomer (69.3%). The plasma protein binding of both enantiomers was saturable over a fivefold range of plasma concentrations. At higher plasma concentrations, the S-enantiomer was less bound than the R-enantiomer. In an in vitro experiment using everted rat jejunum, no chiral inversion was discernible. The dependency of the AUC ratio of the enantiomers on the route of administration may be due to stereoselective first pass metabolism. PMID- 8343344 TI - Enantioselective determination of hydroxychloroquine and its major metabolites in urine and the observation of a reversal in the (+)/(-)-hydroxychloroquine ratio. AB - A sequential achiral-chiral high-performance liquid chromatographic system has been developed for the quantitation in urine of the enantiomers of hydroxychloroquine (HCQ), and of its 3 major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ). HCQ and its metabolites were separated and quantified on a cyano-bonded phase, and the enantiomeric ratios were determined using a Chiral-AGP chiral stationary phase. The assay validation and application of this method to a preliminary study in a human volunteer are presented. In this subject, the initial 0-4 h urine contained the 2 HCQ enantiomers in a ratio of (+)-HCQ:(-)-HCQ of 3:2; by the 2,064 h of the study, this ratio had reversed to (+)-HCQ:(-)-HCQ of 3:7. PMID- 8343345 TI - Testicular atrophy as a risk of inguinal hernioplasty. PMID- 8343346 TI - [Suppurative complications in acute pancreatitis]. AB - The authors examining suppurative complications caused by acute necrotizing pancreatitis point out how such complications can arise early at the same time of acute pancreatitis with large spread in peripancreatic tissues and spaces and with worse prognosis or have a late appearance with a trend to localize and circumscribe. Four cases of pancreatic abscess, three of which largely diffused brought to death in spite of surgery, are reported. PMID- 8343347 TI - [The diagnostic and therapeutic problems of endocrine tumors of the digestive system: our experience]. AB - The authors experience in the surgical treatment of endocrine tumours of the digestive tract is reported. Particularly, they emphasize that in spite of the several syndromes associated with these neoplasms, diagnostic and therapeutic concepts herein analyzed are similar. PMID- 8343348 TI - [Colorectal pathology: an analysis and comparison between patients of different ages]. AB - The increasing incidence of large bowel diseases observed in the last years is age-related. The authors have analyzed 366 patients who underwent surgery for colorectal pathology, divided in two groups (> or < 65 years) considering sex, diagnosis, type of clinical presentation, incidence and type of associated pathology, and post-operative complications. The analysis of the series revealed that type of clinical presentation, surgical patterns, post-operative infections were the same in the two groups, as reported in the literature. The substantial differences were only due to the different incidence of colo-rectal pathology, associated pathology and cardiovascular complications, factors that become characteristic of the elderly patients. PMID- 8343349 TI - [A case of multiple intestinal perforations due to TBC in a female patient with HIV-1 infection]. AB - The authors report a case of HIV-1 infection, primary miliary tuberculosis of the lung and secondary intestinal tuberculosis complicated with multiple intestinal perforations. The surgical emergency therapy, supported by specific antitubercular drugs, antibiotics, and total parenteral nutrition, consisted in suturing seven perforative sites of the small and large intestine. The Authors stress the possibility that in the future tubercular complications up till now considered atypical may become more and more frequent because of the HIV-1 infection association. PMID- 8343350 TI - [Arteriomegaly: a clinical case report and review of the literature]. AB - The authors report a case of arteriomegaly and underline the importance of a correct diagnosis. A review of the literature, in fact, confirms the incidence of the disease is higher than usually believed. Therefore, a complete diagnostic evaluation is necessary to recognize the disease and assure the adequate treatment. PMID- 8343351 TI - [The use of fibrin glue in the surgery of breast carcinoma]. AB - Twenty-four patients operated on for breast carcinoma with associated axillary node dissection were randomly assigned to two protocols. In the first group fibrin glue was applied intraoperatively, in the second group no complementary treatment was accomplished. The aim of the study was to evaluate the effect of fibrin glue in reducing postoperative axillary sero-lymphatic secretion. In the fibrin glue group a significant reduction of postoperative axillary secretion was observed. PMID- 8343352 TI - [Mediastinoscopy in a general surgery department. The evaluation of 186 cases]. AB - A series of 186 cases of mediastinoscopy performed in a department of general surgery is reported. The main indications for this procedure are: histological diagnosis of mediastinal masses, definition of bronchopulmonary neoplasms and thoracic esophagus ones with indication for surgery. The results obtained are: sensibility 90.3%, complications 3.7%, mortality rate 0%. The authors believe in the great utility of mediastinoscopy in case of unknown histotype of primary neoplasms and CT N2? involvement. PMID- 8343353 TI - [The use of scintigraphy with labelled leukocytes: our experience]. AB - The authors describe various applications of scintigraphy with labeled leukocytes and its value in the diagnosis of gut diseases such as Crohn's disease, ulcerative colitis and related complications. Furthermore, the study of vascular prosthesis infection, cryptogenetic fever and abdominal sepsis, three cases of which are herein reported, is facilitated. The method, in conjunction with endoscopy and traditional radiology, revealed to be of great value in terms of sensitivity and specificity for the diagnosis of the aforementioned diseases. Therefore, the use of such method is encouraged in all those cases of abdominal sepsis of uncertain interpretation and in the evaluation of vascular prosthesis infection. PMID- 8343354 TI - [Anterograde laparoscopic cholecystectomy: when and why]. AB - Today largely diffused is the concept that laparoscopic cholecystectomy (LC) represents the treatment of choice for symptomatic gallstones. Nonetheless some questions have been raised on the real safety of this new method in terms of procedure-related complications. On the basis of our experience with traditional open cholecystectomy, we have recently performed a prograde LC in those cases with difficulties in identifying the anatomical structures of the so called Calot's triangle. This alternative route can be easily performed laparoscopically and has been useful in reducing the time of the intervention in the most difficult setting and to increase the safety of the procedure. The technical details and the results are compared with those of the laparoscopic retrograde route. PMID- 8343356 TI - Rediscovering caring and healing arts. Interview by Alex Mathieson. PMID- 8343355 TI - Normothermic liver perfusion ex situ: a resuscitation tool for hepatic grafts damaged by warm ischemia. AB - Ex situ perfusion of the liver has been proposed as a preservation tool for organs to be grafted; in this study, we have investigated whether this procedure could help to reverse damage caused by prolonged ischaemia. The liver was explanted from 6 pigs under general anaesthesia. The organs were subject to warm ischaemia (37 degrees C) for 30 min., cooled in situ by portal infusion of Euro Collins, excised and maintained ischaemic at 4 degrees C for 30 min. more. Afterwards, normothermic perfusion was achieved through the portal vein and hepatic artery for 6 hrs. The parameters measured allowed to follow up the hemodynamic, metabolic and structural response of the liver to the experimental procedure. By electron microscopy, generalized hepatocyte damage was observed after ischaemia, but appeared to be reversed in most cells after ex situ perfusion. Wide areas of sinusoidal walls were devoid of endothelial lining; where this was present, however, it was normal in structure. Kupffer and Ito cells had normal structure whenever observed. Four livers were implanted orthotopically into recipient animals, which were monitored for hemodynamic and biochemical parameters during surgery and followed up to one week. Post mortem examination was performed on the animals which died before this end point. Two of them were alive after one week. Two animals died, one for a perforation of the right hepatic vein and the other for massive necrosis of the left lobe with sepsis and hemorrhage. These results indicate that normothermic ex situ perfusion of the liver has the potential to become a valuable tool to reverse ischaemic injury and monitor organ function before grafting. PMID- 8343357 TI - Nursing in Canada: researching nurses' work. PMID- 8343358 TI - Strategic thinking. The Royal College of Nursing Research Advisory Group. PMID- 8343359 TI - Mental health day units: users' views. AB - This article describes clients' perspectives on psychiatric day care units in an area in the South of England. The results of a small-scale research project show that clients from different localities have similar perspectives and feelings about the units. It is demonstrated that, in the clients' view, the units achieve many of their aims and fulfil needs that supersede the initial purpose. PMID- 8343360 TI - Health promotion: preventing unwanted teenage pregnancies. AB - In the second of two articles looking at health promotion projects addressing targets set out in the Health of the Nation White Paper (1), the author describes the work of a North Staffordshire family planning clinic which specifically targets young people with contraceptive advice and services including pregnancy testing, rubella vaccination and cervical cytology. Hundreds of young people have attended the clinic since it opened in 1990 and the scheme has been so successful that a similar clinic has been opened in another area. PMID- 8343361 TI - Bedside charts: how to introduce change. AB - This article describes the efforts of an orthopaedic nursing team to scrutinize and reform the charts used at bedside. A review of the process revealed a ritualistic system that was ill-defined and centered around nurses' work patterns. A new chart was designed incorporating features of the old, and adding new information that was considered useful. The author reports that staff preferred the new design and argues that nurses can initiate change at ward level. PMID- 8343362 TI - Portakabinly correct. PMID- 8343363 TI - Roger Dyson. Interview by Trevor Clay. PMID- 8343364 TI - Women's network. Rising stars. PMID- 8343365 TI - Never mind the quality. PMID- 8343366 TI - Misconduct allegations. Victim of false accusations. PMID- 8343367 TI - Government backing for HIV research. PMID- 8343369 TI - Speak up. PMID- 8343368 TI - Disappearance of hospital chaplains. PMID- 8343370 TI - Nursing unions slam MPs ignorance on AIDS issues. PMID- 8343371 TI - Prison nursing: doing time the hard way. PMID- 8343372 TI - Poll positions at the Palace. PMID- 8343374 TI - Shifting patterns of nurses' work. PMID- 8343373 TI - Books used on Project 2000 courses. PMID- 8343375 TI - Rheumatoid arthritis: effects on the family. AB - The impact of rheumatoid arthritis (RA) on the families of people with the disease is poorly understood. A qualitative study was undertaken on 22 patients with rheumatoid arthritis, their respective well partners and their 40 children. For most children the effect of living with a parent suffering from a painful, chronic illness was not detrimental, but a minority suffered verbal and physical abuse. The disease had wide-ranging effects on sexual and working relationships, but marriage to a partner with RA did not result in a threat to the relationship for the majority. Recommendations for future practice are made. PMID- 8343376 TI - 'Ordinariness' in nursing: a study (Part 1). AB - This is the first of two articles describing aspects of ordinariness in nursing as they were explored in a phenomenological study on clinical nursing. By way of introduction, it provides an overview of the first phase of the study in terms of its background and method, and describes aspects of ordinariness, showing their relevance to nursing practice. In exploring this phenomenon, this study affirmed a shared sense of humanity as a general group and the enhancing effect this affinity can have on interpersonal relationships. PMID- 8343377 TI - Workwise: they axed my ward. PMID- 8343378 TI - AIDS focus. Bereavement counselling in HIV disease. PMID- 8343379 TI - AIDS focus. 'How are you? I'm fine'. PMID- 8343380 TI - AIDS focus. HIV roundup. PMID- 8343381 TI - Pressure sores: a case to answer (continuing education credit). PMID- 8343382 TI - Health and safety. The back injury battle. PMID- 8343383 TI - Community care reforms: team spirit. PMID- 8343384 TI - Harvesting of organs: the nursing issues. AB - The RCN Congress of 1991 discussed the ethics of harvesting' organs from patients who are brainstem dead but whose organs are being kept viable (through technological means) to enable them to be removed for transplantation. This review of the legal, ethical and nursing implications of organ harvesting is intended to act as a framework for local discussion and policy formulation. PMID- 8343385 TI - Promoting continence in Denmark and UK. AB - This article compares nursing approaches to the promotion and management of continence in the UK and Denmark. Semi-structured interviews of key health professionals in Denmark were undertaken. The information collected forms the basis for a comparison of clinical practice, management, education and research. PMID- 8343387 TI - 'Ordinariness' in nursing: a study (Part 2). PMID- 8343386 TI - Bereavement counselling (continuing education credit). PMID- 8343389 TI - Information technology. Small is bountiful. PMID- 8343388 TI - Uniform thinking. PMID- 8343390 TI - Will to die. PMID- 8343391 TI - Professional accountability: too scared to care. PMID- 8343392 TI - Purchasing: never mind the quality. PMID- 8343393 TI - Workwise: a moving story. PMID- 8343394 TI - Fear for AIDS wards' future. PMID- 8343395 TI - Funds cut as AIDS increases. PMID- 8343396 TI - A call for mandatory HIV testing. PMID- 8343397 TI - Alcohol consumption and HIV/AIDS warning. PMID- 8343398 TI - Antigens might protect against HIV. PMID- 8343399 TI - The Allitt case: getting close to the facts? PMID- 8343400 TI - Whistleblowers: the end of the affair. PMID- 8343401 TI - Nurses' knowledge of infection control. AB - The article is based on a research study examining infection control in nurse education and practice. A survey of a large population was carried out to establish the perceived importance of microbiological knowledge to nurses and to ascertain whether this knowledge was present. The results suggest that although microbiological knowledge is considered necessary for safe infection control practice, nurses' actual knowledge falls far short of the level required for 'informed' practice. What this implies in relation to patient care, and recommendations regarding education and practice, are discussed. PMID- 8343402 TI - Open learning in nurse education. AB - Much confusion surrounds the meanings of terms such as flexible learning, distance learning and open learning. In this article, the author highlights the difference between these types of learning and their advantages and disadvantages, and stresses the importance of all grades of nurses adopting the philosophy behind the initiative. PMID- 8343403 TI - When can nurses refuse to care? AB - At the RCN Congress in Blackpool last year, one of the key topics discussed was the policy and practice implications which arise if nurses refuse to care for certain patients or if patients refuse to be cared for by a particular nurse. This article outlines the guidance by the RCN Ethics and Nursing Committee on when patients and nurses can exercise a right to refuse to be cared for or provide care. PMID- 8343404 TI - Learning disabilities. Community homes: institutions in waiting? AB - This article explores the assumption that community care is better than care in an institution for people with learning disabilities. Parallels are also drawn with community provision of residential and nursing home accommodation for people who are elderly, those who have a physical handicap, and people with a mental illness. While community care is recognised as a valuable option, the authors argue that it must be correctly implemented, and identify the need to move further forward. PMID- 8343405 TI - Mental health: benefits of holidays for hostel ward residents. AB - This article describes a self-catering holiday in Ireland for a group of new 'long-stay' hostel residents from a psychiatric hospital, and accompanying staff. It looks at the process of organising the trip, analyses the benefits and assesses the lessons learned. PMID- 8343406 TI - Computer reviews. Why pay more? PMID- 8343409 TI - Tradimus. Personal finance: the banks that like to mumble 'maybe'. PMID- 8343407 TI - Tradimus. Student power: any way--we're poor. PMID- 8343408 TI - Tradimus. Personal finance: not to be taken for granted. PMID- 8343410 TI - Tradimus. Examinations: examinations fail the test. PMID- 8343411 TI - Tradimus. Qualification: the right staff? PMID- 8343412 TI - Quality assurance. Setting new standards. PMID- 8343413 TI - Quality assurance. Talk about teaming up. PMID- 8343414 TI - Quality assurance. Unchartered initiatives at Cameron Hospital. PMID- 8343415 TI - Quality assurance. Quality control: is patient power the solution? PMID- 8343416 TI - Quality assurance. Getting some important heads together. PMID- 8343417 TI - Annual Scientific Meeting of the British Society for Haematology. Bournemouth, 20 23 April 1993. Abstracts. PMID- 8343418 TI - Death rates of miners and ex-miners with and without coalworkers' pneumoconiosis in south Wales. 1955. PMID- 8343419 TI - Mortality among workers in the diatomaceous earth industry. AB - A cohort mortality study was conducted among workers from two plants in the diatomaceous earth mining and processing industry in California. Diatomaceous earth consists of the skeletal remains of diatoms. Exposure to amorphous (non crystalline) and crystalline silica in the form of quartz results from open pit mining and exposure to crystalline silica (principally cristobalite) occurs in the processing of the material. Lung cancer and non-malignant respiratory diseases have been the health outcomes of greatest concern. The main study cohort included 2570 white men (533 Hispanic and 2017 non-Hispanic workers) who were employed for at least 12 months cumulative service in the industry and who had worked for at least one day during the follow up period, 1942-87. Vital status was ascertained for 91% of the cohort and death certificate information was retrieved for 591 of 628 (94%) identified deaths. The all causes combined standardised mortality ratio (SMR) was slightly increased (SMR = 1.12; 628 observed) compared with rates among US white males. The principal contributors to this excess were increased risks from lung cancer (SMR = 1.43; 59 observed) and non-malignant respiratory disease (NMRD) excluding infectious diseases and pneumonia (SMR = 2.59; 56 observed). The excess of lung cancer persisted when local county rates were used for comparison (SMR = 1.59). Internal rate comparisons by Poisson regression analysis were conducted to assess potential dose-response relations for lung cancer and NMRDs. Mortality trends were examined in relation to duration of employment in dust exposed jobs and with respect to an index of cumulative exposure to crystalline silica. The crystalline silica index was a semiquantitative measure that combined information on duration of exposure, differences in exposure intensity between jobs and calendar periods, the crystalline content of the various product mixes, and the use of respiratory protection devices. Increasing gradients of risk were detected for lung cancer and NMRD with both exposure indices. The relative risk trends for lung cancer and NMRD with crystalline silica exposure lagged 15 years were respectively: 1.00, 1.19, 1.37, and 2.74, and 1.00, 1.13, 1.58, and 2.71. Based on a review of available but limited data on cigarette smoking in the cohort and from application of indirect methods for assessing confounding variables, it seems unlikely that smoking habits could account for all of the association between exposure to dust and lung cancer. The intense and poorly controlled dust exposures encountered before the 1950s were probably the most aetiologically significant contributors to risks from lung cancer and NMRDs. The absence of an excess of lung cancer among workers hired since 1960, and the finding of no deaths attributed to pneumoconiosis as an underlying cause of death among workers hired since 1950 indicate that exposure reductions in the industry during the past 40 years have been successful in reducing excess risks to workers. Further mortality follow up of the cohort and the analysis of radiographic data will be needed to determine conclusively the long term patterns of disease risks in this industry. PMID- 8343420 TI - Incidence of renal stones among cadmium exposed battery workers. AB - The health effects of occupational exposure to cadmium were studied in a group of 902 workers employed for at least one year in a Swedish battery factory between 1931 and 1982. Data on air cadmium concentrations for different periods were combined with company employment records to obtain individual cumulative exposure estimates. A questionnaire including questions on the occurrence of kidney stones was sent to all 601 living workers and to the next of kin of 267 of the deceased workers. The response rate was 88%. 73 workers reported renal calculi that appeared after initial employment. A dose-response relation was found between cumulative exposure to cadmium and age standardised cumulative incidence. Incidence rate ratios (IRRs) were then computed for three exposure categories (< 250, 250- < 5000, and 5000 micrograms/m3 x years) standardised for calendar time, age, and smoking with the low exposure group as reference level. The IRRs were 1.0, 1.6 [95% confidence interval (95% CI) 0.7-3.4], and 3.0 (95% CI 1.3-6.8) respectively. beta 2 Microglobulin measurements were available for 33 workers who formed stones; 13 of these workers had tubular proteinuria (beta 2 microglobulin > or = 34 micrograms/mmole creatinine)--that is, a prevalence of 39%. There was also an indication of a steeper dose-response relation among workers with tubular proteinuria. PMID- 8343421 TI - A nine year follow up study of renal effects in workers exposed to cadmium in a zinc ore refinery. AB - Renal changes with time have been studied in 14 workers engaged in the production of cadmium (Cd) in a zinc ore refinery. These workers were examined once a year in the period 1980 to 1985 and 13 of them also in 1989. Four of the workers (group A) had been employed in an old Cd plant before 1973 and had received higher exposures to Cd than the other workers (group B). Average urinary Cd concentrations over the whole study period in workers of group A ranged from 6.9 to 9.2 micrograms/g creatinine (median 8.4 micrograms/g) and in workers of group B from 0.64 to 7.1 micrograms/g creatinine (median 1.9 micrograms/g). Renal effects were assessed by the determination of urinary N-acetyl-beta-D glucosaminidase (NAG), beta 2-microglobulin (beta 2-M), retinol binding protein, albumin, total protein, and serum creatinine concentrations and activity. Urinary beta 2-M concentrations in three of four workers of group A were close to or marginally above the upper normal limit during the study period. The beta 2 microglobinuria was not, however, progressive. No values outside normal limits were detected for any of the other renal tests in workers of groups A and B, related to exposure to Cd. Dose-response relations showed that urinary Cd correlated significantly with urinary NAG activity and total protein and beta 2 M. The earliest change induced by Cd was seen for urinary NAG activity within normal limits of NAG excretion. The regression lines were similar in the surveys between 1981 and 1989, indicative of no progression to higher values for any of the renal tests. The current biological exposure index (BEI) of 10 micrograms/g creatinine for workers exposed to Cd, set by the American Conference of Governmental Industrial Hygienists (ACGIH), therefore seems justified, although the safety margin is small. The World Health Organisation recommended limit and ACGIH (1992-3) proposed limit of 5 micrograms/g creatinine would provide a much larger safety margin, and could be regarded as an action point for increased health surveillance. PMID- 8343422 TI - Residual cognitive deficits 50 years after lead poisoning during childhood. AB - The long term neurobehavioural consequences of childhood lead poisoning are not known. In this study adult subjects with a documented history of lead poisoning before age 4 and matched controls were examined with an abbreviated battery of neuropsychological tests including measures of attention, reasoning, memory, motor speed, and current mood. The subjects exposed to lead were inferior to controls on almost all of the cognitive tasks. This pattern of widespread deficits resembles that found in children evaluated at the time of acute exposure to lead rather than the more circumscribed pattern typically seen in adults exposed to lead. Despite having completed as many years of schooling as controls, the subjects exposed to lead were lower in lifetime occupational status. Within the exposed group, performance on the neuropsychological battery and occupational status were related, consistent with the presumed impact of limitations in neuropsychological functioning on everyday life. The results suggest that many subjects exposed to lead suffered acute encephalopathy in childhood which resolved into a chronic subclinical encephalopathy with associated cognitive dysfunction still evident in adulthood. These findings lend support to efforts to limit exposure to lead in childhood. PMID- 8343423 TI - Estimation of individual dermal and respiratory uptake of polycyclic aromatic hydrocarbons in 12 coke oven workers. AB - Twelve workers from a coke plant in The Netherlands participated in an intensive skin monitoring programme combined with personal air sampling and biological monitoring during five consecutive eight hour workshifts. The purpose of the study was to make a quantitative assessment of both the dermal and respiratory intake of polycyclic aromatic hydrocarbons (PAHs). Pyrene was used as a marker compound for both dermal and respiratory exposure to PAHs. The biological measure for the internal exposure to PAHs was urinary 1-OH-pyrene concentration. Measurements on exposure pads at six skin sites showed that mean total skin contamination of the 12 workers ranged between 21 and 166 micrograms pyrene a day. The dermal uptake of pyrene ranged between 4 and 34 micrograms/day, which was about 20% of the pyrene contamination on skin. The mean concentration of total pyrene in the breathing zone air of the 12 coke oven workers ranged from 0.1 to 5.4 micrograms/m3. The mean respiratory uptake of pyrene varied between 0.5 and 32.2 micrograms/day. Based on the estimates of the dermal and respiratory pyrene uptake it is concluded that an average 75% (range 28%-95%, n = 12) of the total absorbed amount of pyrene enters the body through the skin. Because of the difference in the pyrene:benzo(a)pyrene ratio between the air samples and the skin contamination samples, the dermal uptake of benzo(a)pyrene was also estimated. This was about 51% of the total absorbed amount (range 8%-92%, n = 12). The total excreted amount of urinary 1-OH-pyrene as a result of exposure to PAHs during the five consecutive workshifts varied between 36 and 239 nmol. A multiple regression model of the mass balance between pyrene dose (both dermal and respiratory) and 1-OH-pyrene excretion confirmed the relevance of the dermal exposure route. The variation in urinary 1-OH-pyrene excretion was determined more by the dermal pyrene dose than by the respiratory dose. The model showed an estimate of the percentage of the absorbed amount of pyrene that is metabolised and excreted as 1-OH-pyrene in urine. For the 12 workers this percentage varied between 13% and 49% depending on smoking habits and consumption of alcohol. The results of this study indicate that among coke oven workers, the skin is the main route of uptake of PAHs. Preventive measures to reduce exposure to PAHs should be focused more on the reduction of dermal contamination by PAHs than on the reduction of inhaled dose. PMID- 8343424 TI - Decreased glutathione content and glutathione S-transferase activity in red blood cells of coal miners with early stages of pneumoconiosis. AB - Blood samples of miners heavily exposed to coal dust were examined for changes in glutathione S-transferase (GST) activity. Decreased GST activity was found in red blood cells of subjects with early stages of coal workers' pneumoconiosis (International Labour Office classification 0/1-1/2) when compared with control miners. At further progression of coal workers' pneumoconiosis (> or = 2/1), the activity of GST was not different from controls. In the same group with moderate coal workers' pneumoconiosis a decrease in GSH in red blood cells occurred. Decreases in GST activity in early stages of coal workers' pneumoconiosis, as well as the decreases in glutathione peroxidase (GPx) activity and in GSH concentrations reported earlier, may originate from damage caused by reactive oxygen species. These changes might imply an impairment of the detoxification capacity for electrophilic and oxidative compounds during this stage of the disease. PMID- 8343425 TI - An improved instrument for the in vivo detection of lead in bone. AB - An improved instrument for the fluorescence excitation measurement of concentrations of lead in bone has been developed. This is based on a large area high purity germanium detector and a point source of 109Cd. The source is positioned in a tungsten shield at the centre of the detector face such that 88keV photons cannot enter the detector directly. In vivo measurements are calibrated with plaster of Paris phantoms. Occupationally non-exposed men show a minimum detectable concentration of about 6 micrograms/g bone mineral. Measurements of tibia lead concentrations in 30 non-occupationally exposed men between the ages of 23 and 73 showed an annual increment of 0.46 microgram/g bone mineral/year. The mean deviation from the regression of tibia lead upon age was 3.5 micrograms/g bone mineral. Tibia lead concentration in one subject with a history of exposure to lead was 69.6 (SD 3.5) micrograms/g bone mineral. The improved precision of the point source large detector system means that greater confidence can be placed on the results of in vivo measurements of lead concentration. This will allow studies of the natural history of non-occupational lead accumulation in normal subjects and should permit investigations of the efficacy of therapeutic interventions in subjects poisoned with lead. PMID- 8343426 TI - Melanoma and occupation: results of a case-control study in The Netherlands. AB - Several studies have reported excesses of risk of melanoma in specific industries. Data from a case-control study in The Netherlands, including 140 cases with a cutaneous melanoma and 181 controls with other types of malignancy, were used to evaluate whether the reported associations with these specific industries could be reproduced. Adjustment for characteristics of pigmentation and exposure to sunlight was made. Increased risks of cutaneous melanoma were found for subjects who had ever worked in the electronics industry (odds ratio (OR) = 2.03, 95% confidence interval (95% CI) 0.63-6.62), in the metal industry (OR = 2.61, 95% CI 0.96-7.10), and in the transport and communication branch (OR = 1.92, 95% CI 0.84-4.35). These ORs were adjusted for age, sex, education, hair colour, tendency to burn, freckling, and exposure to sunlight. No increased risks were seen for workers in the chemical industry, the textile industry, and among health care workers. Analyses according to duration and latency of exposure did not give consistent results, but existing patterns may be obscured by the imprecision of the estimates. PMID- 8343427 TI - Mortality and incidence of cancer among sewage workers: a retrospective cohort study. AB - To study the incidence of and mortality from cancer among sewage workers a retrospective analysis was performed on a cohort of 656 men employed for at least one year at any one of 17 Swedish sewage plants during the years 1965-86. Assessment of exposure was done by classification of work tasks. Lower than expected total mortality (standardised mortality ratio (SMR) = 0.75, 95% confidence interval (95% CI) 0.58-0.97) and cardiovascular mortality (SMR = 0.61, 95% CI 0.39-0.91) was found. This was interpreted as a result of the healthy worker effect. For all cancers combined the mortality (SMR = 1.08, 95% CI 0.68 1.67) and morbidity (SMR = 1.02, 95% CI 0.72-1.38) were comparable with those of the general population. There were increased incidences for brain tumours (SMR = 2.19, 95% CI 0.45-6.39), gastric cancers (SMR = 2.73, 95% CI, 1.00-5.94), and renal cancers (SMR = 1.68, 95% CI = 0.35-4.90). For lung cancer the risk was reduced (SMR = 0.70, 95% CI 0.15-2.05). Allowance for a latency period of 10 years from the start of exposure did not change the pattern. Logistic modelling was used to search for exposure-response relations. In a logistic model with the confounder age forced in, renal cancer had a significant positive relation with a weighted sum of employment times, where the weights describe the classification of exposure. No exposure-response relations were found for brain tumors or gastric cancers. The increased risks are based on small numbers of cases. A future follow up will add more conclusive power to the study. Specific exposures need to be identified to allow for a better dose-response analysis. PMID- 8343429 TI - Seamstress's finger. PMID- 8343428 TI - Follow up study of workers exposed to man made mineral fibres. AB - A survey of workers in seven man made mineral fibre (MMMF) production plants, the subject of a previous report, was conducted, with other blue collar workers serving as regional comparisons. Based on the median reading of chest radiographs by five readers, a low prevalence of small opacities, all at the 1/0 and 1/1 profusion levels, was again found: for workers with MMMFs, 23/1435 (1.6%); for comparison workers, 2/305 (0.7%). Spirometric measurements indicated generally healthy populations, and were not related to presence of opacities. Ninety three per cent (21/23) of MMMF workers with opacities worked at the two plants with the highest exposures to fine fibres, resulting in a dose-response relation across plants. For one location, the prevalences of opacities for the MMMF and comparison workers were not significantly different (5.9% (13/220) v 3.1% (2/65)). No comparison x ray films were obtained for the MMMF plant with the highest prevalence (6.6%), so a second phase of the study was conducted, with pre employment films from these two plants. On this second reading, the prevalence of opacities was lower; there were no significant differences between the two groups of films, and no relation between opacities and exposure indices. There was considerable inter and intrareader variability. These results indicate no adverse clinical, functional or radiographic signs of effects of exposure to MMMFs in these workers. PMID- 8343430 TI - Hexachlorophene exposure in a young patient with soft tissue sarcoma. PMID- 8343431 TI - Asbestos and cancer: history and public policy. PMID- 8343432 TI - Quantitative morphological assessment of erythroblastic differentiation induced, in vitro, in human K562 leukemic cells. AB - K562 human leukemia cell line undergoes in vitro terminal differentiation towards the erythroid pathway following treatments with appropriate chemical agents including aclacinomycin, fagaronine and hemin. These three drugs induced a different expression of phenotypic and functional characters associated with differentiation. The morphological characteristics of the differentiation sequences elicited by these agents were evaluated by image analysis using a SAMBA 200 cell image processor. Multivariate statistical analyses of morphological data revealed that only aclacinomycin was able to induce significant modifications of the morphological parameters similar to those observed during the maturation of normal bone-marrow erythroblastic cells. These data correlate with the higher inductive potency of aclacinomycin as compared to hemin or fagaronine and suggest that quantitative cytology may be a useful adjunct to conventional tests for the selection of new drugs with differentiating potential. PMID- 8343433 TI - Effectiveness of pulse-shape criteria for the selection of dicentric chromosomes by slit-scan flow cytometry and sorting. AB - A method was developed to detect dicentric chromosomes by slit-scan flow cytometry. The two centromeres of dicentric chromosomes are represented by the two dips in the trimodal fluorescence profile. A trimodal profile can, however, also be generated by aggregates of chromosomes. We tested the effectiveness of slit-scan profile criteria that were applied to discriminate between trimodal profiles generated by dicentrics and trimodal profiles generated by artefacts. A Profile-Dip Counter (PDC) module was designed that can assess, in real time, the number of dips in slit-scan profiles. The PDC module was used in combination with a Cytofluorograph System 50 cell sorter for slit-scan sorting of chromosomes prepared from irradiated V79 cells. Chromosomes corresponding to trimodal profiles were sorted individually onto slides for subsequent visual inspection by fluorescence microscopy. The isolated chromosomes were stretched by treatment with trypsin to increase the efficiency for centromere detection. When fixed with glutaraldehyde, chromosomes could be sorted intact on slides. We found that trimodal profiles are generated by dicentric chromosomes as well as by monocentric and aggregated chromosomes. When stringent pulse-shape criteria were applied for the selection of profiles, the yield of dicentric chromosomes was 70% of the sorted chromosomes. PMID- 8343434 TI - Application of multivariate, fuzzy set and neural network analysis in quantitative cytological examinations. AB - Multivariate statistical methods have been used in several studies to increase the diagnostic reliability of TV image analyser systems. In recent years some algorithms for decision support (fuzzy logic) and for pattern recognition (neural nets), both non-linear, were developed. This paper reports on preliminary results obtained with these methods in quantitative cytology and compares them to the traditional classifiers. A total of 21 normal, 15 dysplastic and 23 malignant, gastric imprint smears were Feulgen stained and analysed on a Leitz Miamed DNA cytophotometer system. Mean DNA content, the 2c deviation index (2cDI), 5c exceeding rate (5cER), G1, S, G2 phase fraction ratios, cell nucleus area and form factor were determined. Diagnostic accuracy of the discriminant analysis was 96% for the malignant cases, 87% for dysplasias and 81% for normal cases. Cluster analysis gave no significant result. Our diagnostic system utilizing fuzzy logic has made the diagnostic borders adjustable and reliable. The back-propagation neural net correctly classified the normal and malignant cases (100%) and all but one of the dysplasias (98%). The non-linear mathematical methods improved the reliability of the diagnostic system. These new algorithms gave results comparable to traditional classifiers. The application of these methods to clinical samples is encouraging. PMID- 8343435 TI - Normalization of the minimum spanning tree. AB - A problem of considerable interest in pattern recognition and data analysis is that of describing the spatial structure of a data set. In the field of biology this could be based on graph construction. Although the minimum spanning tree (MST), contains less information than the Relative Neighbourhood, Gabriel and Delaunay graphs [16], this graph has been frequently used [3-9]. The MST is a subgraph of all the preceding graphs. Two main types of parameters can be derived from a graph. Some of the parameters are derived from the structure of the graph (topological parameters), whereas others are based on the Euclidean metrics of the graph (edge lengths). Since these parameters are used to characterize the spatial structure of data sets, they have to be normalized so that different biological structures may be compared. A model for the normalization of the most common parameters derived from the MST is thus presented here. Two aspects of the problem are considered: (i) omission of the metrics associated dimension of the Euclidean parameters in order to compare biological structures at different scale factors and (ii) elimination of border effects to avoid border artefacts. PMID- 8343436 TI - Refractive laser sharing concepts proliferate. PMID- 8343437 TI - Aspheric photorefractive keratectomy with excimer laser. AB - BACKGROUND: Increased spherical aberration of the cornea is a common finding after excimer laser keratorefractive keratectomy. The shape of the paracentral cornea is probably related to the incidence of side effects like glare and halos at night depending on ablation zone size and pupil diameter. Aspheric curvature changes of the paracentral cornea at the edge of the ablation may decrease those side effects. MATERIALS AND METHODS: Fifteen patients were treated with photorefractive keratectomy for myopia correction with a Summit excimer laser (Summit Technology, Waltham, Mass), one eye using a standard spherical algorithm and the fellow eye using a new aspherical algorithm. Eyes were followed for 6 to 18 months. RESULTS: None of 15 patients reported halos in the aspherically corrected eye stronger than in the fellow eye, whereas five patients claimed stronger halos in the spherically corrected eye. The effective clear zone size was 3.16 +/- 0.35 mm in the spherical cases compared to 3.43 +/- 0.31 in the aspherical cases, although the same ablation zone diameters of 5 mm were used. This difference is highly statistically significant. Effective spherical aberration based on raytracing analysis of the central 5 mm of the corneal topographic maps was significantly smaller in the corneas with aspheric correction than in those with spheric corrections. CONCLUSION: These results indicate better optical homogeneity in eyes after aspheric photorefractive keratectomy for myopia compared to standard spherical corrections. PMID- 8343438 TI - Shape and radius of posterior corneal surface. AB - BACKGROUND: The posterior corneal surface is often ignored in predictive models concerned with refractive surgery. In previous studies, the radius of this surface has been measured in a variety of ways, primarily over a large chord diameter of the surface, with the common assumption that the surface is spherical. The asphericity of this surface has not been adequately addressed in the past. METHODS: An algorithm is derived for the calculation of posterior corneal surface apical radius and using characteristics of the anterior corneal surface and topographic corneal thickness variation. Anterior corneal asphericity was measured using a commercially available photoelectric keratoscope. Using a marked soft contact lens, a simple method of locating noncentral corneal sites is described as an aid to ultrasonic pachometry. RESULTS: In a group of 20 normal subjects ranging in age from 19 to 23 years, the average posterior corneal surface apical radius and asphericity (p) was 5.80 mm (SD = +/- 0.42) and 0.64 (SD = 0.37) for the vertical meridian, and 5.82 mm (SD = +/- 0.40) and 0.52 (SD = 0.30) for the horizontal meridian. Average central corneal thickness was 533 mu (SD = +/- 19). CONCLUSIONS: The average asphericity values are below 1, hence the posterior corneal surface is described as a flattening ellipse. The rate of flattening of this surface is greater than the rate of flattening along the averaged anterior corneal surface. PMID- 8343439 TI - Proceedings of the 1st Keratoprosthesis Study Group Meeting. Miami, Florida, November 6, 1992. Abstracts. PMID- 8343441 TI - Nomenclature for keratoconus suspects. PMID- 8343440 TI - Combined epikeratoplasty and homoplastic keratophakia for correction of aphakia: double curve effect. AB - BACKGROUND: Having used the nonfreeze Barraquer-Krumeich-Swinger set for refractive lamellar keratoplasty since January 1987, the authors found the results of this procedure to be disappointing for correction of aphakia. Insufficient refractive gains for epikeratoplasty (+39% of initial refraction at 12-month follow up) persuaded the authors to look for a more effective refractive corneal surgery technique for correcting aphakia. METHODS: We describe a new technique consisting of the insertion of a plano-convex homoplastic donor cornea meniscus between the patient's cornea and a hypermetropic epikeratoplasty. A nonfreeze Barraquer-Krumeich-Swinger set was used to fashion the two donor lenticules. This double surgery, called the "double curve effect," because it uses two convex surfaces to increase the converging power of the cornea, has been performed in 15 eyes. RESULTS: We report the results of 10 eyes with a 6-month follow up. The average refractive gain was +11.75 D, 90% of the needed correction. But there was a loss of approximately 46% of best spectacle-corrected visual acuity. CONCLUSION: Three problems should be emphasized: the existence of two interfaces, the difficulty of perfectly centering the two lenticules, and the induced irregular astigmatism. Despite these problems which can reduce the level of best spectacle-corrected visual acuity, the double curve effect may offer an effective solution for treating certain cases of unilateral aphakia. PMID- 8343442 TI - Should we consider clear lens extraction for routine refractive surgery? PMID- 8343443 TI - More radial keratotomy comments. PMID- 8343444 TI - Hexagonal keratotomy. PMID- 8343445 TI - [Autologous tumor killing (ATK) and tumor metastasis in human cancer patients]. AB - The present study has demonstrates that the ability of blood lymphocytes to kill freshly isolated tumor cells tested at the time of surgery predicts a favorable clinical course in patients who have primary localized solid tumor and receive curative operation. The strong correlation of autologous tumor killing (ATK) activity with tumor-free interval and total survival indicates that ATK activity is a meaningful prognostic indicator and provides evidence for immunological control of tumor growth and metastasis. According to these data, it is unlikely that cancer patients who remain tumor-free after 5 years of follow-up will develop recurrence or die from the disease. While there is no direct evidence that ATK effector cells play a critical role in regression of tumor and prevention of tumor metastasis and regrowth, the lack of ATK activity in patients who relapsed and died after surgery may not result from factors related to their poor performance status and other immunological functions since no differences have been observed in background factors between ATK-positive and-negative groups. The prognostic value of ATK activity in patients with documented metastatic tumors has not been established yet. In this respect, however, the induction of ATK activity by biological therapy has positively correlated with prolonged survival time, while such a correlation is not observed with other parameters such as NK cells or LAK cell activity. Based on the clinical and biological significance of ATK activity, clinical trials have been conducted to determine whether the induction of ATK activity before surgery by administration of BRM could improve the clinical outcome in patients who naturally have no such potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343446 TI - [The roles of cytokine in organ-specific tumor metastasis]. AB - The production of cytokines by tumor cells has been suggested as the molecular perturbation responsible for the development of malignant tumors. The behavior of tumor cells in animals is presumed to be affected by these factors, which include such hematopoietic cytokines as GM-CSF, IL-1, and IL-6. Here, we report findings demonstrating that GM-CSF is produced by many murine transplantable tumors with metastatic ability in the lungs, and IL-6 and/or IL-1 are produced by the tumors metastatic in the liver. We discuss the notion that the particular organ or organs in which tumor cells metastasize may be associated with the type of cytokines produced by the tumors. Metastatic spread requires interactions of tumor cells with components of the extracellular matrix of host tissues or with other cells, almost all of which depend on cell surface determinants such as cell adhesion molecules. We also discuss the possibility that the expression and adhesive potentials of adhesive protein (CD44) may be regulated by the cytokine (GM-CSF) excreted from the tumor cells. We then emphasize the possibility that both gene expression of cytokines and adhesive proteins play a critical role in tumor metastasis and in determining organ specificity in metastasis. PMID- 8343447 TI - [Establishment and characterization of a cell line (H-1) from squamous cell carcinoma of human gingiva--effect of temperature]. AB - We established a cell line (H-1) from human oral cancer. It was derived from a biopsy specimen of squamous cell carcinoma in the lower gingiva of a japanese man. The cell line has now been growing in vitro for more than 86 passages. The cells had an epithelial morphology and grew as adherent monolayers. PAS stain was positive and activity of ALP also was positive. They had a doubling time of 37 hours and colony formation of 32%. Chromosomal numbers ranged from 49 to 75 and the modal number was 61. The cell line was tumorigenic in nude mice, its histologic examination showed identification with that from the original tumor. The cells were sensitive to hyperthermia. PMID- 8343448 TI - [Serum-free culture for leukemia cells]. AB - Several human and murine acute myeloid leukemia cell lines growing in serum-free and protein-free culture medium are known to be established. In this paper, recent development of serum-free and protein-free culture methods for leukemia cells and the characteristics of the established cell lines are reviewed. Chemically defined culture medium is preferable as compared with serum-containing culture medium because the latter contains various, undefined factors which make it difficult to investigate the interactions between cell proliferation or differentiation and various growth factors. Investigations using leukemia cell lines which are maintained in a serum-free and protein-free chemically defined medium will provide the important information with respect to cell biology of leukemia cells and leukemia therapy. PMID- 8343450 TI - [Detection of chromosomal numerical aberration in glioma by FISH (fluorescence in situ hybridization)]. AB - FISH method with chromosome specific DNA probe to interphase nuclei has been useful for the analysis of chromosomal numerical aberration in human brain tumor. We applied the FISH method to 9 gliomas and one glioma cell line (KMU-100) with 4 kinds of chromosomes of number 7, 9, 10 and 17. The predominant specific aberration in glioma were revealed the increased signal numbers of chromosome 7&17 and the decreased signal numbers of chromosome 9&10. The inactivation of tumor suppressor genes and the activation of oncogenes have been suggested as the principal mechanism of tumorigenesis in human cancer. The definite oncogenes have not still been identified on chromosome 7&17 and tumor suppressor genes on chromosome 9&10. We discussed the mechanism of tumorigenesis with one or more oncogenes on chromosome 7&17 and of one or more tumor suppressor genes on chromosome 9&10 in glioma. PMID- 8343449 TI - [Establishment and characterization of a human rectal cancer cell line, SRM from primary diffuse infiltrating type cancer]. AB - Primary diffuse infiltrative cancer of the large bowel shows poor prognosis. A human rectal cancer cell line, designated as SRM, was established from the metastatic lymph node of a 35-year-old female patient. SRM cells have been cultured with RPMI-1640 medium supplemented with 10% fetal calf serum and grew as monolayers, showing a tendency to pile up. The doubling time of this cell line was 23.0 hours, and the modal number of chromosomes was 64 at passage 14. The cells produced CA19-9 and TPA in the spent medium and formed tumors in nude mice, the histology of which was similar to that of the primary tumor. CA19-9 in the cytoplasma of the transplanted tumor cells was demonstrated by the ABC method and the c-myc oncogene was amplified in the transplanted tumor in nude mice. PMID- 8343451 TI - [Regulation of tumor metastasis and invasion by fibroblasts]. AB - Using immunodeficient mice human tumor cell lines, which metastasize to specific organs from orthotopic implantation sites but not from ectopic sites, have been established. We have been studying mechanisms of the regulation of tumor metastasis by organ specific microenvironments, and have recently found significant differences in interactions between metastatic tumor cells and fibroblasts from different tissues. Fibroblasts isolated from orthotopic organ tissues of nude mice enhanced invasion of metastatic human colon carcinoma cells. In contrast, fibroblasts derived from a subcutaneous tissue suppressed carcinoma cell invasion. These divergent effects were found in part due to differential expression of cytokines and growth factors by fibroblasts from different tissues. PMID- 8343452 TI - [Worm recovery rate and small intestinal lesions of albino rats coinfected with Fibricola seoulensis and Metagonimus yokogawai]. AB - Worm recovery rates and pathologic changes in small intestine of albino rats were observed after concurrent and challenge infections with metacercariae (MC) of Fibricola seoulensis and Metagonimus yokogawai, and compared with those of single infection groups. Albino rats in concurrent infection group were killed 20 days after feeding with 1,000 MC of each fluke. Rats in challenge infection group were fed with 1,000 MC of F. seoulensis and challenged by 1,000 MC of M. yokogawai 10 days after primary infection, then killed 10 days thereafter. In concurrent infection group, mean number of F. seoulensis and M. yokogawai recovered, 250 and 118 respectively, were similar to those of single infection groups. However, more flukes were collected from the duodenum and less flukes were from the ileum than from single infection group. In challenge infection group, the recovery rate of F. seoulensis was similar to that of single infection group and the distribution of the flukes was similar to that of concurrent infection group. Mean number of M. yokogawai, 69, was significantly lower than that of single infection group. Its distribution, however, extended to the duodenum and most of the flukes were recovered from the jejunum. In concurrent infection group, villi of the duodenum were more markedly thickened, fused and shortened than those in F. seoulensis single infection group. The crypt epithelium appeared to be hyperplastic and inflammatory cell infiltration into the villous stroma was mild. Villous atrophy in the jejunum and ileum was milder than in M. yokogawai single infection group. In challenge infection group, the findings were similar to those of concurrent infection group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343453 TI - [Proteinase activity in the isolates of Trichomonas vaginalis according to their pathogenicity]. AB - Ten axenic isolates of Trichomonas vaginalis were subcutaneously injected to the BALB/c mice in order to assess their pathogenicity by means of so-called "mouse assay" method. All the isolates revealed neutral and acid proteinase activities both in their lysates and in culture media, but the specific activities of both proteinases in the severely pathogenic group were significantly higher than the mildly pathogenic group (p < 0.05). In the SDS-PAGE system in which the electrophoretic gels contained 0.4% gelatin as the substrate, five different banding patterns of trichomonal proteinases were detected, and the patterns were closely related with the pathogenicity of the isolates of T. vaginalis. All five bands might be regarded as cysteine proteinases group in the inhibitor assays. The cytotoxicity of the lysates of T. vaginalis to the target Chinese hamster ovarian (CHO) cell line was also significantly different according to the pathogenicity of the isolates, and generally lower in the lysates treated with cysteine proteinase inhibitors than in the control lysates. In summarizing the results, it might be considered that the proteinases of T. vaginalis showing five electrophoretic banding patterns are closely related with the pathogenicity and cytotoxicity of the isolates of T. vaginalis. PMID- 8343454 TI - Mucosal mast cell responses to experimental Metagonimus yokogawai infection in rats. AB - Intestinal mucosal mast cell (MMC) responses were studied in rats experimentally infected with Metagonimus yokogawai (Digenea: Heterophyidae). Twenty Sprague Dawley rats were fed each 2,500 metacercariae isolated from the sweetfish and sacrificed on the week 1, 2, 3 and 4 post-infection (PI). Recovery of worms was performed from the small intestine of each rat. To visualize the MMCs, duodenal and jejunal (upper, middle and lower) tissue sections were made and stained with alcian blue/safranine-0. The average worm recovery rates were 16.2% and 13.8% on the week 1 and week 2, respectively, but they decreased rapidly to 4.1% and 4.2% on the week 3 and week 4 PI, respectively, which indicate spontaneous worm expulsion after the week 2. The MMC number in the infected rats was, compared with uninfected controls, significantly increased in the whole small intestine, through the whole period of observation. The peak level of mastocytosis was observed on the week 3 PI. It is strongly suggested that MMCs might be involved in the expulsion process of flukes from the rat intestine. PMID- 8343455 TI - [Infectivity of the sparganum treated by praziquantel, gamma-irradiation and mechanical cutting]. AB - An experimental study was performed to observe the infectivity of sparganum (plerocercoid of Spirometra erinacei) treated by praziquantel, gamma-irradiation and mechanical cutting. The spargana were obtained from the naturally infected European grass snake, Rhabdophis tigrina, or from the experimentally infected mice. A total of 83 mice (ICR strain) were divided into 3 experimental groups by the source of the damage, fed each with 5 spargana, and sacrificed 1 month later for worm recovery. In the praziquantel group, the worms were incubated in the concentration of 10 micrograms/ml (control: Tyrode for 4 hours) for 0.5, 1, 2 and 4 hours at 36 degrees C, and fed to mice. The recovery rate from mice in praziquantel group was not different from that (80%) of control group and in the range of 76-100%. In the gamma-irradiation group, the worms were irradiated by 10 1000 Gy with Cs137. The average recovery rates of 69-100% were not different from that of control up to 100 Gy. The rate was 56% under 150 Gy, and 5% by 1000 Gy. In the mechanical cutting group, the worms were cut at 0.5, 1, 2 and 3 mm from the anterior end of the scolex. The average recovery rates in each group were 70 90% and that of control was 90%. The present finding suggests that the sparganum be highly resistant to praziquantel, gamma-irradiation and mechanical cutting. The vitality center of the sparganum must be at the anterior end of its scolex. PMID- 8343456 TI - Serodiagnosis of human paragonimiasis by ELISA-inhibition test using monoclonal antibodies. AB - ELISA-inhibition test using Paragonimus westermani specific monoclonal antibody (Mab) was investigated to improve the diagnostic specificity of paragonimiasis. By cell fusion, one hybridoma clone secreting anti-P. westermani specific Mab was selected (Pwa-14), which reacted on bands of 28 kDa, 42.5 kDa, 89 kDa and 120.5 kDa. IFA showed Pwa-14 was located at the vitelline follicles. By micro-ELISA, 100% of 22 paragonimiasis cases were found positive, but 5 of 40 clonorchiasis cases (12.5%), 3 of 26 cysticercosis cases (7.7%) showed false positive. None of 10 sparganosis patients or 28 normal controls reacted positively. On the other hand, by ELISA-inhibition test using a P. westermani specific Mab, 100% of paragonimiasis cases were found positive, and there were no positive in cysticercosis, sparganosis cases or normal controls, except 2 (5.0%) false positive sera of 40 clonorchiasis cases. The ELISA-inhibition test using a Mab showed higher specificity in comparison with micro-ELISA for serodiagnosis of human paragonimiasis. PMID- 8343457 TI - Serodiagnosis of cysticercosis by ELISA-inhibition test using monoclonal antibodies. AB - Monoclonal antibodies (Mabs) were produced against crude scolex extract of T. solium metacestodes, and applied to ELISA-inhibition test for improving the specificity of serodiagnosis of human cysticercosis. Four hybridomas secreting species-specific anticysticercal Mabs (Cya-1, Cya-7, Cya-28 and Cya-31) were selected. Each Mab reacted on antigenic components of 25.5 kDa (Cya-1), 28 kDa (Cya-7), 87.5 kDa (Cya-28), and 12.5 kDa (Cya-31). IFA showed that Cya-1 was located at the calcium corpuscles, and Cya-7 at the loose connective tissue of T. solium metacestode scolex. Cya-28 and Cya-31 reacted on the tegument of the scolex. By conventional ELISA, 23 out of 28 (82.1%) cysticercosis patients were found serologically positive, but 1 out of 9 (11.1%) sparganosis cases and 6 out of 31 (19.4%) paragonimiasis cases showed false positives. By ELISA-inhibition test using species-specific anti-cysticercal Mab Cya-7, 19 out of 28 (67.9%) cysticercosis cases were found serologically positive, but there were no false positives in other parasitic infections. PMID- 8343458 TI - [The effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mother]. AB - Acanthamoeba culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalitis (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive immunity on the active immunization in offspring mice have not been demonstrated. This experiment was done to observe the effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mothers. Acanthamoeba culbertsoni was cultured in the CGV medium axenically. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba culbertsoni trophozoites 1 x 10(6) each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated intranasally with 1 x 10(4) trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T cell/Ly2+ T cell ratio was increased in the transferred immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of immunization. PMID- 8343459 TI - Activities of acid phosphatase and non-specific esterase are present in the tribocytic organ and the caecum of Fibricola seoulensis. AB - In order to know the enzyme activities of Fibricola seoulensis, an intestinal trematode of human and rodent in Korea, the enzyme histochemical method is applied. Activities of acid phosphatase (E.C.3.1.3.2) and non-specific esterase (E.C.3.1.1) were present in microvilli and glandular cells of tribocytic organ and the epithelium of the caecum. PMID- 8343460 TI - Turnover of biliary epithelial cells in Clonorchis sinensis infected rats. AB - We performed bromodeoxyuridine (BrdU) staining to observe the proliferation pattern of epithelial cells on the biliary mucosa in Clonorchis sinensis infection. Albino rats were infected with 100 metacercariae each and their livers were processed for histopathological observation after BrdU injection. Five to six sites in the liver of a rat were selected for paraffin section, and stained immunohistochemically to visualize BrdU incorporating cells. The flukes were mainly in the common bile duct and right or left hepatic bile ducts. The proportion of stained epithelial cells in the infected bile ducts where the worms were found on the section was 2.9-10.2% at 1 week after infection, 7.3-12.8% at 2 weeks, 7.3-13.4% at 5 weeks, and 8.4-14.8% at 15 weeks while in the non-infected ducts 0 to 2.7% cells were stained. The stained cells were mainly at the base of the mucosal layer. It is suggested that mucosal epithelial cells of the bile ducts infected with C. sinensis become hyperplastic mainly by direct and local stimulation of the worms. PMID- 8343461 TI - Experimental infection of Paragonimus westermani in mice and rats. AB - To determine the infectivity and maturity of metacercariae of Paragonimus westermani after keeping at low temperature for a long period, 45 mice and 45 rats were each infected with 20 metacercariae which were kept at 4 degrees C for 8 to 234 days. The worm recovery in mice increased with age of worm and reached a peak of 32% at 41-50 days and then decreased with age. The rate in rats first decreased to a lowest point of 6% at 71-100 days and then increased with age. In 42 infected mice and 41 infected rats, 187 immature worms (183 tiny and 4 juvenile ones) and 190 worms (164 tiny, 19 juvenile and 7 mature ones) were recovered respectively. Two worm cysts with eggs only and 8 empty worm cysts were also found in the rats. In addition, the frozen metacercariae can still develop to mature worms in SD rats. PMID- 8343462 TI - An epidemiological study of metagonimiasis along the upper reaches of the Namhan River. AB - An epidemiological study of Metagonimus infection was undertaken along the upper reaches of the Namhan River, with special consideration on the species (type) of the worms collected from humans. Eggs of Metagonimus spp. were detected from 15 (9.7%) of 154 people examined in Umsong-gun, and from each infected person (5 cases) 6,015-24,060 worms (mean 13,233) were recovered after treatment with praziquantel (10 mg/kg). Eggs were also detected from 37 (48.1%) of 77 people in Yongwol-gun, from whom (27 cases) 1-4,965 worms (means 1,215) were collected. The worm from Umsong-gun consisted of both Metagonimus Miyata type and Metagonimus takahashii, whereas those from Yongwol-gun consisted of only Metagonimus Miyata type. When the uterine eggs of the two kinds and M. yokogawai (obtained from people in Tamjin River basin) were morphologically compared, it was suggested that the egg size should be a good indicator for discrimination of the species or type. The source of human infection was proved to be fresh water fishes; 49 of 52 Zacco platypus examined, 6 of 8 Hemibarbus longirostris, 13 of 15 Pseudogobio esocinus, 4 of 6 Odontobutis obscura interrupta, and 17 of 18 Carassius carassius were found infected with Metagonimus metacercariae. From the results, it is concluded that the upper reaches of the Namhan River are endemic foci of Metagonimus Miyata type and M. takahashii. PMID- 8343463 TI - The evolving role of visual electrodiagnostics. PMID- 8343464 TI - Blindness in the developing world. PMID- 8343465 TI - Age-related Bruch's membrane change: a clinical study of the relative role of heredity and environment. AB - For many years there has been controversy concerning the role of genetic influences in the pathogenesis of age-related macular disease. It is widely believed that the lesions causing visual loss occur in response to age-related changes in Bruch's membrane which are recognised clinically as drusen. In this study the density, size, and confluence of drusen as shown on colour photographs were compared in eyes of 50 spouses and 53 sibling pairs ascertained during a prospective study of age-related macular disease. Concordance between pairs of drusen--number, size, and density-were determined by kappa statistic and chi 2 test for trend. Drusen were absent in one sibling and 26 spouses of patients. There was a trend towards concordance of drusen characteristics between siblings but not between spouses, although the difference achieved 5% significance only for the number and density of drusen in the central macula. The difference of concordance between the probands and spouses and the probands and siblings was significant for all characteristics. These findings support the belief that genetic factors influence age-related changes in Bruch's membrane. They also imply that environmental factors are less important or alternatively that the environmental variation between households included in our study was not great enough to be evident. PMID- 8343466 TI - Cone dystrophies with negative photopic electroretinogram. AB - A scotopic electroretinogram with an a-wave amplitude larger than the b-wave amplitude traditionally is termed 'negative'. Six male patients with negative photopic electroretinograms were examined; three of them suffered from progressive cone dystrophy, in which negative electroretinograms are unusual. Another patient without symptoms was the brother of a patient with cone dystrophy. These patients are compared with others who characteristically have negative electroretinograms-one patient with incomplete congenital stationary night blindness and another with X linked congenital retinoschisis. Differential diagnosis between these unusual cases of cone dystrophies and X linked retinoschisis or congenital stationary night blindness was possible with funduscopy, adaptometry, and evaluation of progression, but not with the electroretinogram. Inner retinal defects may occur in cone dystrophies as indicated by the negative electroretinogram. The waveform variations between our patients may be due to different inner retinal defects. The findings in two brothers indicate that cone dystrophy and inner retinal defects may be inherited separately. PMID- 8343467 TI - Blindness in Africa: Zimbabwe schools for the blind survey. AB - An ophthalmic assessment survey of 430 students in Zimbabwe's two schools for the blind was conducted in 1988. Bilateral corneal opacity was found to be responsible for 75% of all blindness among institutionalised blind students. Thirteen per cent of the study patients could gain improved vision through either ocular surgical intervention or spectacle correction. Findings in this survey are similar to those from other schools for the blind elsewhere in Africa. PMID- 8343468 TI - Congenital glaucoma in the West Bank and Gaza Strip. AB - This study presents the results of all patients with congenital glaucoma who were managed at St John Ophthalmic Hospital, Jerusalem from 1981 to 1990. This involved 118 eyes, 174 surgical procedures, and 460 examinations under anaesthesia. All procedures showed decreasing success rates with time. However, trabeculectomy was clearly the most successful in the hands of general ophthalmologists. Careful, long term follow up with particular regard to both intraocular pressure and detection and treatment of amblyopia are emphasised. PMID- 8343469 TI - A population based, prospective study of the development of ROP in prematurely born children in the Stockholm area of Sweden. AB - A prospective population based study including 260 children with a birth weight of 1500 g or less was performed in the Stockholm county. The total incidence of retinopathy of prematurity (ROP) was 40.4%, while severe ROP--that is, stage 3 or more, was seen in 20.0%. Cryotherapy was performed in 10.8%. Logistic regression analysis revealed independent association of both gestational age and birth weight with ROP. The association of gestational age and ROP was significantly stronger, indicating that the degree of immaturity of the eye is a main predictive factor for the development of ROP. The purpose of a general screening for ROP is to identify children requiring cryotherapy. Based on these results it seems appropriate to include children with a gestational age of 32 weeks or less in such a programme and a first examination at 5-6 weeks of postnatal age is suggested. PMID- 8343470 TI - Monocular temporal hemianopia. AB - Monocular temporal hemianopia was identified in 24 patients. The field of the fellow eye was normal. Computed tomography or magnetic resonance imaging showed juxta-sellar lesions in 19 patients. Fifteen had pituitary adenomas, two had tuberculum sella meningiomas, one a craniopharyngioma, and one an astrocytoma. One patient had optic neuritis. A relative afferent pupillary defect (RAPD) was detected in most patients. Field loss was functional in two. Two had congenital optic disc dysversion with hemianopia which did not respect the vertical meridian. Monocular temporal hemianopia is attributed to involvement of the ipsilateral optic nerve close enough to the chiasm to selectively impair conduction in crossing nasal retinal fibres from the ipsilateral eye, but too anterior to affect crossing nasal retinal fibres from the contralateral eye. The combination of an RAPD, with or without optic disc pallor, on the side of monocular temporal field loss implicates compression of the optic nerve at its junction with the chiasm. PMID- 8343471 TI - Suture needle drainage of subretinal fluid. AB - A simple technique is described for the transcleral drainage of subretinal fluid during retinal detachment repair. In a prospective study of 94 consecutive suture needle drainage procedures subretinal fluid was successfully drained in 91 cases. There were six 'significant' subretinal haemorrhages associated with the procedure, but none was subfoveal in location or directly compromised the surgical outcome. In no case was retinal incarceration or retinotomy observed. PMID- 8343472 TI - Decreased choroidal thickness in eyes with secondary angle closure glaucoma. An aetiological factor for deep retinal changes in glaucoma? AB - A decreased count of retinal photoreceptors all over the fundus and a loss of retinal pigment epithelium cells mainly in the parapapillary region have been reported to be associated with glaucoma. This study addressed the question whether this cell loss in the deep retinal layers may be connected with a change of the choroidal thickness in glaucomatous eyes. Histological sections of 12 eyes with secondary angle closure glaucoma due to a malignant melanoma of the ciliary body and 20 eyes with a malignant choroidal melanoma and normal intraocular pressure were histomorphometrically evaluated. Before enucleation the intraocular pressure was significantly higher in the glaucoma group compared with the control group. Thickness of the choroid was measured at 12 locations from the posterior pole to the fundus periphery. The choroid was significantly thinner in the glaucoma group than in the control group. The decreased choroidal thickness was mainly due to a diminished choroidal vessel diameter. The differences were more marked at the optic disc border than in the fundus periphery. The decreased choroidal thickness in the glaucomatous eyes suggests a reduced choroidal perfusion. It fits with the reported lack of autoregulation of the choroidal blood circulation. Considering the diminished choroidal thickness especially in the parapapillary region, it may be one among other factors explaining the changes of the deep retinal layers in eyes with glaucoma. It indicates that thinning of the choroid, besides the chorioretinal atrophy in the parapapillary region, should be added to the panoply of histological changes in glaucoma. PMID- 8343473 TI - Role of mitomycin C in pterygium surgery. AB - Mitomycin C in the form of eye drops in a concentration of 0.4 mg/ml (0.04%) was used as adjunctive treatment for primary and recurrent pterygium after surgical excision. The study was concurrent in nature and consisted of 32 pterygia in 30 patients and was done over a period of 36 months. The object was to observe the effect of mitomycin C drops on pterygium recurrence after surgical excision. Fifteen eyes of 15 patients were treated with 'bare sclera technique' for pterygium excision. Nine patients showed recurrence occurring within first 6 months of surgery. On the other hand 17 eyes of 15 patients after bare sclera pterygium excision received mitomycin 0.4 mg/ml (0.04%) eye drops four times a day for 2 weeks from first postoperative day. There was no recurrence of pterygium in this group. Follow up time for these cases ranged from 13-19 months. PMID- 8343475 TI - Primary surgery for primary open angle glaucoma--justified or not? PMID- 8343476 TI - Adult nasolacrimal duct bypass tubes: where do they go? PMID- 8343474 TI - Does autoimmunity to S-antigen play a role in Fuchs' heterochromic cyclitis? AB - Autoimmunity directed against retinal or choroidal antigens has been suggested to play a role in the chorioretinal lesions observed in patients with Fuchs' heterochromic cyclitis. This hypothesis was addressed and patients with Fuchs' heterochromic cyclitis were tested for cellular immunity (migration inhibitory factor assay) against human retinal S-antigen. A significantly higher percentage of patients with Fuchs' heterochromic cyclitis had a positive cellular autoimmune response to S-antigen than healthy controls and other patients with anterior uveitis. This finding is remarkable since Fuchs' heterochromic cyclitis is generally classified as an anterior uveitis and patients with Fuchs' heterochromic cyclitis without chorioretinal lesions also had a positive test. In view of these results and a sensitisation against a corneal antigen reported earlier in Fuchs' heterochromic cyclitis, it is suggested that a chronic low grade grade anterior uveitis or chorioretinitis of unknown origin may cause the release of potent autoantigens in these patients. PMID- 8343477 TI - Simultaneous retinal and optic nerve lesions in toxoplasmosis: the advantages of magnetic resonance imaging. PMID- 8343478 TI - Focal electroretinogram and visual field defect in multiple evanescent white dot syndrome. PMID- 8343479 TI - Contralateral active ocular toxoplasmosis in Fuchs' heterochromic cyclitis. PMID- 8343480 TI - Resolution of an external layer macular hole associated with an optic nerve pit after laser photocoagulation. PMID- 8343481 TI - A case of presumed congenital herpes zoster ophthalmicus. PMID- 8343482 TI - Orbital multiple myeloma mimicking acquired angio-oedema. PMID- 8343483 TI - Amaurosis fugax in young adults. PMID- 8343484 TI - Glaucoma, ocular hypertension, cataract, and glucose tolerance. PMID- 8343485 TI - 5-Fluorouracil and ocular toxicity. PMID- 8343486 TI - Fractured laser fibreoptic cord. PMID- 8343487 TI - Iris crystals and uveitis. PMID- 8343488 TI - ACE inhibition with perindopril and atherogenesis-induced structural and functional changes in minipig arteries. AB - The effects of angiotensin-converting-enzyme (ACE) inhibition on atherosclerosis induced changes in arterial function are unknown, as well as whether they are coupled to improvements of structural alterations in the arterial wall. An atherogenic (A) diet and the ACE inhibitor perindopril (P) were given concomitantly for 4 months to seven adult Pitman-Moore minipigs (7 months of age; A+P animals), which were compared with seven A and seven control (C) animals. Perindopril, at a daily dose of 4 mg PO that is commonly used in the clinical setting, induced a continuous 70% inhibition of serum ACE activity. At the end of the study, the atherosclerosis-induced impairment of arterial flow was investigated via the hemodynamics and vascular rheology of hindlimb arteries in non-barbiturate-anesthetized pigs. Structural alterations were evaluated from the histopathology of lesions in the arterial tree (abdominal aorta, left interventricular coronary artery [LIVCA], and brachiocephalic trunk [BCT]), with particular attention given to the analysis of the structure and composition of aortic elastic fibers. Atherosclerosis impaired the function of both capacitance and resistance arteries. Blood pressure (BP) rose significantly because of increased hindlimb peripheral resistance (HPR) and aortic input impedance (Zc), although blood flow was not affected. Altered aortic stress and elastic responses revealed that the stiffness of the aorta was markedly increased because of increased wall tension and reduced viscoelasticity, the viscous component being blunted in the arterial wall. Perindopril significantly opposed these alterations by reducing BP, HPR, and Zc and by returning parietal stiffness values to C values by increasing aortic compliance. ACE inhibition prevented the alteration of both stress and elastic responses. Major fibroproliferative fatty lesions were observed in the aorta and LIVCA, while moderate fibrosclerotic lesions were found in the BCT. Computerized densitometric analysis of orcein-stained elastin showed that elastic laminae fragmentation was prominent in the abdominal aorta, less in the LIVCA, and moderate in the BCT. Furthermore, the elastin content was reduced in the atherosclerotic aorta, although this loss of elastin was not associated with changes in the biochemical nature of alkali-insoluble elastin. Perindopril significantly prevented the development of atherosclerosis in the abdominal aorta, LIVCA, and BCT by decreasing the cross-sectional area of lesions as well as the number of lipid-laden cells in the abdominal aorta and LIVCA. In the abdominal aorta, ACE inhibition significantly prevented the alteration of elastic laminae by specifically preventing elastolytic fragmentation of dense elastic laminae, but it didn ot modify elastin content.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8343489 TI - Plasma lipid, lipoprotein cholesterol, and apoprotein distributions in selected US communities. The Atherosclerosis Risk in Communities (ARIC) Study. AB - The distributions of plasma lipids, lipoproteins, and apoproteins of 14,524 female and male black and white participants 45 to 64 years old in the Atherosclerosis Risk in Communities (ARIC) Study are presented. All specimens were analyzed at a central laboratory. Mean total cholesterol levels increased with increasing age across all ages from 204 to 229 mg/dL (12%) in women and from 208 to 213 mg/dL (2%) in men. Triglyceride levels increased with age in women, remained stable in men, and were higher in whites than blacks. High-density lipoprotein (HDL) cholesterol levels were higher in black and white women (range, 57 to 59 mg/dL) compared with black men (49 to 52 mg/dL) or white men (42 to 43 mg/dL). Cholesterol associated with HDL was distributed in a relatively constant proportion between HDL3 (70% to 76%) and HDL2 (24% to 30%) for all race/sex groups. Low-density lipoprotein (LDL) cholesterol levels increased with age in black (14.7%) and white (17.1%) women and in black (4.4%) and white (3.7%) men; more than 50% of all participants had LDL cholesterol levels > 130 mg/dL. Apoprotein A-I and B levels followed the same trends as HDL cholesterol and LDL cholesterol levels, respectively. Lipoprotein(a) [Lp(a)] levels were twice as high in blacks as in whites, and women's Lp(a) levels were higher than men's Lp(a) levels for each race. Menopause was associated with elevated total cholesterol, LDL cholesterol, apoprotein B, and Lp(a) levels, and hormone replacement medication use in postmenopausal subjects was associated with higher HDL cholesterol, triglyceride, and apoprotein A-I levels and lower LDL cholesterol, apoprotein B, and Lp(a) levels. PMID- 8343490 TI - Aggregate formation is more strongly inhibited at high shear rates by dRGDW, a synthetic RGD-containing peptide. AB - The effect of D-Arg-Gly-Asp-Trp (dRGDW), a synthetic RGD-containing peptide, on platelet adhesion and aggregate formation on various purified adhesive proteins and the extracellular matrix of endothelial cells was investigated with anticoagulated blood recirculating through a parallel-plate perfusion chamber. Aggregate formation on the extracellular matrix of phorbol myristate acetate (PMA)-stimulated endothelial cells and on collagen type I was more strongly inhibited by dRGDW at higher shear rates than at a low shear rate. Platelet adhesion to the extracellular matrix of nonactivated and PMA-stimulated endothelial cells was inhibited by dRGDW, especially at high shear rates, probably as a consequence of the inhibition of platelet spreading. Inhibition by dRGDW of platelet adhesion to von Willebrand factor, fibronectin, and fibrinogen was almost complete, indicating that platelet adhesion to these substrates is mediated through RGD-directed receptors. Platelet adhesion to laminin was not inhibited by the peptide, whereas platelet adhesion to collagen was increased as a consequence of the inhibition of aggregate formation. Our results show that dRGDW is a strong inhibitor of platelet adhesion and aggregate formation, especially at high shear rates. PMID- 8343491 TI - Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits. AB - The possible activity of ticlopidine and its analogue clopidogrel in early atherogenesis was investigated. Incubation of rabbit platelets with the extracellular matrix produced by endothelial cells in culture induced massive platelet adherence in vitro. This phenomenon was strongly reduced when platelets were isolated from rabbits that had been treated with a single dose of clopidogrel (10 mg/kg PO) or three doses of ticlopidine (each 200 mg/kg PO) (94% and 56% inhibition of platelet adhesion, respectively). Three doses of aspirin (each 200 mg/kg PO) were ineffective. Air-drying injury of the rabbit carotid artery resulted in platelet adherence to the underlying subendothelium. This platelet accumulation on the damaged vessel wall was greatly reduced by clopidogrel: 95% (P < .001) inhibition of platelet adhesion after a single oral dose of 25 mg/kg. Ticlopidine (200 mg/kg) was also effective (71% inhibition; P < .001), whereas aspirin (100 mg/kg PO) failed to reduce platelet adhesion to the subendothelium. The effect of clopidogrel on intimal smooth muscle hyperplasia in rabbit carotid arteries subjected to air-drying endothelial injury was then investigated. After a 16-day treatment, clopidogrel (25 mg/kg per day PO) inhibited the development of intimal thickening (48% inhibition; P < .01). This effect was dose dependent and increased with the duration of the treatment. Under the same experimental conditions, ticlopidine (200 mg/kg per day PO) inhibited myointimal thickening (57%; P < .001), whereas aspirin was ineffective. These results show that clopidogrel and ticlopidine, two ADP-selective antiplatelet agents, can reduce myointimal thickening after endothelial injury. This effect can be due to the inhibition of platelet adhesion and aggregation to the exposed subendothelium. PMID- 8343492 TI - Noninvasive quantitative evaluation of atherosclerosis using MRI and image analysis. AB - A new medical image analysis system to quantify atherosclerosis in the lower abdominal aorta using magnetic resonance imaging is described. This medical image analysis and display system permits the quantification of the three-dimensional (3D) properties of the vessel wall and lumen cross-sectional area and volumes. Preliminary results of employing this medical image analysis capability on magnetic resonance images demonstrated a twofold increase in wall volume per unit vessel length, corresponding to intimal thickening, before luminal narrowing was detected. This work demonstrated the feasibility and usefulness of quantitatively evaluating the 3D properties of the vessel lumen and wall by using a combination of magnetic resonance imaging and image analysis. The demonstration that intimal wall thickening is observed in images before observable occlusion of the lumen can be expected to provide an important early indicator of the future development of atherosclerosis. Such capability will permit detailed and quantitative studies to assess the effectiveness of therapies, such as drug, exercise, and dietary regimens. PMID- 8343493 TI - Relation of plasma triglyceride and apoB levels to insulin-mediated suppression of nonesterified fatty acids. Possible explanation for sex differences in lipoprotein pattern. AB - To test whether a sex difference in insulin-mediated suppression of nonesterified fatty acids (NEFAs) could account for sex differences in plasma triglyceride levels, we studied 632 normoglycemic men and women of European and South Asian descent aged 40 to 69 years. Mean fasting NEFA levels were 19% higher in women than in men. Between fasting and 2 hours after a 75-g oral glucose load, NEFA levels fell by 69% in women and 55% in men, so that mean NEFA levels at 2 hours after loading were 19% lower in women than in men. Plasma triglyceride and apolipoprotein B levels were correlated with 2-hour NEFA levels in each sex and ethnic group, and these associations were independent of glucose, insulin, and central obesity. These results are consistent with experimental studies of the effects of insulin and NEFAs on hepatic production of triglycerides and apolipoprotein B. Suppression of NEFA levels in response to insulin is greater in women than in men, and this may account for some of the sex differences in lipoprotein pattern and coronary heart disease risk. PMID- 8343494 TI - Local intimal-medial uptakes of 125I-albumin, 125I-LDL, and parenteral Evans blue dye protein complex along the aortas of normocholesterolemic minipigs as predictors of subsequent hypercholesterolemic atherogenesis. AB - This report describes the normalized intimal-medial uptakes [uptake (M, mg.cm-2) divided serum concentration (c0, mg.cm-3)] of 125I-albumin, 125I-low-density lipoprotein (LDL), and in vivo Evans blue dye (EBD)-albumin complex as functions of pressure (P), time (t), molecular species (i), and location (z) along a ventral longitudinal z axis of the normal, intact, aortic endothelial surface in adult normocholesterolemic Sinclair Research Farm (SRF) minipigs and compares these uptake (M/c0) measurements with atherogenesis in hypercholesterolemic cohorts. Uptakes of porcine serum 125I-albumin (n = 21) and 125I-LDL (n = 10) were measured in freshly excised, metabolically supported aortas using a recently developed organ-support system. In vivo intimal-medial EBD uptake vs z data were measured photometrically on opened descending aortas from another group (n = 6) of normocholesterolemic, adult, SRF minipigs 18 hours after the intravenous administration of EBD. For comparison purposes, the corresponding incidence of atherosclerotic lesions along the aortic z axis was calculated using topographic data from hypercholesterolemic minipig cohorts (n = 39). The results showed that uptakes varied greatly with t, z, and macromolecule (i) but not with P. More specifically, the value of M/c0 at any location (z) rose with t, was insensitive to P, decreased with macromolecular (i) size, and varied with z in a pattern that "peaked" in the upstream region, decreased to a nadir in the downstream region, and then rose again as it approached the abdominal celiac orifice. The spatially z-averaged uptake rates for the three different labeled serum proteins were 0.31 x 10(-3) cm.h-1 for 125I-albumin, 0.42 x 10(-3) cm.h-1 for EBD-albumin, and 0.04 x 10(-3) cm.h-1 for 125I-LDL. Nondimensionalized analysis of the individual sets of uptake data indicated that the overall uptake relationship [M(t,P,z,i)/c(io), cm] could be characterized empirically by the simple product of two separate functions: one, a "scaling function" [m(z,i)], that described the uptake magnitude for a given i and z and appeared to be independent of t or P; the other, a "shape function" [s(t,P)], that described the shapes of the uptake vs t and P relationships and appeared to be independent of z or i. The "scaling function" [m(z,i)] vs z contour appeared to correlate well with the corresponding atherosclerotic lesion incidence vs z contour from the group of hypercholesterolemic minipig cohorts. Assuming passive transport, it was shown ("Appendix") that m(z,i) can be interpreted physically in terms of an endothelial diffusive permeability coefficient (P,cm.s-1).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8343495 TI - Associations of fish intake and dietary n-3 polyunsaturated fatty acids with a hypocoagulable profile. The Atherosclerosis Risk in Communities (ARIC) Study. AB - Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors--fibrinogen, factor VII, factor (vWF), protein C, and antithrombin III--in four population-based samples totaling over 15,000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 microgram/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors. PMID- 8343496 TI - Dermatan sulfate inhibition of fibrin-rich thrombus formation in nonhuman primates. AB - Dermatan sulfate (DS), a factor that amplifies plasma heparin cofactor II antithrombin (HCII) activity, has been evaluated in baboons for its relative antithrombotic and antihemostatic effects by use of a model that combines both platelet-rich and fibrin-rich thrombus formation. Thrombus was generated in a two component thrombogenic device incorporated into exteriorized femoral arteriovenous shunts, in which a proximal segment of collagen-coated tubing induces platelet-rich arterial-type thrombus and distal expanded chambers with disturbed and static flow produce fibrin-rich venous-type thrombus. Thrombus formation was measured as the deposition of autologous 111In-platelets by imaging analysis and by the accumulation of 125I-fibrin. Intravenous infusion of DS at 0.83, 8.3, and 42 mg/kg maintained plasma levels at approximately 7, 70, and 400 micrograms/mL, respectively, throughout the period of study. By enhancing HCII dependent inactivation of soluble thrombin, DS prolonged the coagulation times, reduced plasma fibrinopeptide A levels, and decreased fibrin-rich thrombus formation in the chamber portion of the device in a dose-dependent manner, ie, the intermediate dose reduced fibrin accumulation by approximately 70% (P < .05). By contrast, neither platelet deposition on collagen nor platelet hemostatic function, assessed with bleeding time determinations, was significantly affected by DS at any dose studied (P > .2 and P > .1, respectively, for the high dose), a finding presumably explained by the resistance of immobilized thrombin to inactivation by DS. PMID- 8343497 TI - Role of endogenous platelet-derived growth factor in arterial smooth muscle cell migration after balloon catheter injury. AB - The process of intimal thickening after de-endothelializing injury to the rat carotid artery is dependent on the migration of smooth muscle cells from the media. Recent reports have suggested that platelet-derived growth factor may be an important mediator of migration after injury. We have addressed this issue by directly determining smooth muscle cell migration in injured arteries of animals depleted of platelets and after administration of an antibody that blocks platelet-derived growth factor. Because there is a reported association between plasminogen activator synthesis and smooth muscle cell migration, we assayed the activity levels of plasminogen activators after arterial injury and also assessed the effect of a plasmin inhibitor on migration. The data suggest that platelet derived growth factor, released by platelets at sites of arterial injury, is an endogenous mediator of smooth muscle cell migration; that plasmin generation, catalyzed by tissue-type plasminogen activator, is necessary for migration; and that one way in which platelet-derived growth factor may act is by stimulation of the synthesis of tissue-type plasminogen activator by smooth muscle cells. PMID- 8343499 TI - The GTP-binding regulatory proteins, Gs and G(i), are altered in erythrocyte membranes of patients with ischemic heart disease resulting from coronary atherosclerosis. AB - Acute ischemic heart disease is associated with alterations in the cardiac adenylate cyclase system response, although the specificity and mechanism of these events are unknown. We studied the characteristics of inhibitory (G(i)) and stimulatory (Gs) GTP-binding regulatory proteins (G proteins) of adenylate cyclase in erythrocyte membranes of patients (n = 16) with nonacute ischemic heart disease resulting from coronary atherosclerosis. Gs was measured by reconstitution with the resolved catalytic unit of adenylate cyclase and by cholera toxin-catalyzed ADP-ribosylation of a 42-kD protein; G(i) was tested as a 41-kD substrate of pertussis toxin-catalyzed ADP-ribosylation. Gs activity was decreased by 27 +/- 2% in the cholate extract and by 25 +/- 3% in the supernatant of guanosine 5'-(gamma-thio)triphosphate-treated membranes. The amount of cholera toxin substrate was decreased by 33 +/- 3%, and the pertussis toxin substrate was increased by 27 +/- 5% compared with healthy subjects (n = 10). All changes in G protein characteristics appear to be specific relative to other erythrocyte membrane proteins and hemoglobin. Those patients who have a decreased Gs possess approximately normal Gi, and those with increased G(i) showed no change in Gs. Patients with increased G(i) (normal Gs) exhibited more severe deterioration of their coronary arteries than did patients with decreased Gs (normal G(i)) (P < .05), but these two groups did not differ significantly in serum lipids, hormones, drug therapy, historical data, or baseline assessment (P < 0.05). PMID- 8343498 TI - Activities of lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma of patients with low concentrations of HDL cholesterol. AB - Previous investigations have shown that abnormalities in the postheparin plasma levels of the lipolytic enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL), are correlated with variations in plasma high-density lipoprotein cholesterol (HDL-C) levels. The present study was performed to determine correlations between the postheparin plasma activities of these two enzymes and HDL levels in a sizable number of subjects with low HDL-C levels. Two types of low-HDL subjects were investigated: 159 male subjects with low HDL-C (< 40 mg/dL) and normal triglyceride (< 250 mg/dL) levels (the low-HDL group) and 80 male subjects with low HDL-C (< 40 mg/dL) and elevated triglyceride (> or = 250 mg/dL) levels (the low-HDL/high-TG group). Postheparin plasma activities of LPL and HTGL were determined in these two groups, and these levels were compared with those obtained from 51 normolipidemic (normal-HDL) male subjects. Postheparin LPL activities were significantly lower in the low-HDL and low-HDL/high-TG groups (mean +/- SD, 9.9 +/- 2.9 and 10.4 +/- 3.0 mmol/h per liter, respectively; P < .001 for both) compared with the normal-HDL group (12.5 +/- 3.7 mmol/h per liter). Conversely, postheparin HTGL activities were significantly higher in the low-HDL and low-HDL/high-TG groups (39.3 +/- 16.2 and 44.4 +/- 16.7 mmol/h per liter, respectively; P < .001 for both) compared with the normal-HDL group (29.7 +/- 11.3 mmol/h per liter). Consequently, mean LPL/HTGL ratios were markedly lower in the two low-HDL groups compared with the normal-HDL group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343500 TI - DNA photolyase repairs the trans-syn cyclobutane thymine dimer. AB - DNA photolyases catalyze the splitting of the cyclobutane ring joining the two dihydropyrimidines of a pyrimidine dimer by a photoinduced electron-transfer reaction. Previous studies concluded that photolyase repairs only the cis-syn form of the eight stereoisomers of the cyclobutane pyrimidine dimer (Pyr[ ]Pyr). In this study we found that Escherichia coli photolyase binds to the trans-syn-I isomer of T[ ]T with about 10(4)-fold lower affinity than the cis-syn isomer but it repairs it relatively efficiently. PMID- 8343501 TI - Comparison of sequence preference of tomaymycin- and anthramycin-DNA bonding by exonuclease III and lambda exonuclease digestion and UvrABC nuclease incision analysis. AB - The DNA bonding sites of two pyrrolo[1,4]benzodiazepine derivatives--tomaymycin (Tma) and anthramycin (Atm)--were identified by exonuclease III (exo III) digestion, lambda exonuclease (lambda exo) digestion, and UvrABC nuclease incision analysis. exo III digestion stalls 4-5 bases 3' to a drug-DNA adduct. While this method can recognize most of the Atm-and Tma-DNA modification sites, it is complicated in that exo III digestion is also stalled by certain unmodified sequences and by drug bound to the opposite strand. lambda exo digestion stalls 1 2 bases 5' to a drug-DNA adduct. The lambda exo method also recognizes most of the drug-DNA bonding sites and renders a cleaner background; however, it is also affected by opposite-strand drug bonding. Due to their intrinsic digestion polarities, these two exonucleases tend to be stalled by the drug-DNA adduct at one end of the DNA molecule. Purified UvrA, UvrB, and UvrC proteins acting together make dual incisions 6-8 bases 5' and 4 bases 3' to a Atm- or Tma-DNA adduct. This nuclease complex recognizes all the Tma- and Atm-DNA bonding sites identified by exonuclease digestion methods, and all the UvrABC incisions can be attributed to drug modifications in the incised DNA strand. The degree of UvrABC nuclease incision increases with increasing drug concentrations for DNA modification. Using the UvrABC incision method, we have identified the sequence preference of Tma- and Atm-DNA adduct formation in three DNA fragments, and we have found that these two drugs have different preferred sites for adduction. Both Tma- and Atm-DNA bonding is strongly influenced by the 5' and 3' neighboring bases; the orders of preferred 5' and 3' bases for Tma are A > G, T > C, and A, C > G, T, and for Atm the orders are A > G > T > C and A > G > T, C. The preferred triplets for Tma bonding are -AGA- > -GGC-, -TGC-, and AGC- and for Atm are -AGA , -AGG- > -GGA-, -GGG-. PMID- 8343502 TI - Electronic nature of the transition state for nucleoside hydrolase. A blueprint for inhibitor design. AB - A new approach to understanding transition-state structure is presented which involves the sequential application of experimental and computational methods. A family of experimentally determined kinetic isotope effects is fit simultaneously in a vibrational analysis to provide a geometric model of the transition state. The electrostatic potential surface of the geometric model is defined by molecular orbital calculations to detail the electronic nature of the transition state. The method provides both geometric and charge information for the enzyme stabilized transition state. Electrostatic potential surface calculations were applied to the N-glycohydrolase reaction catalyzed by nucleoside hydrolase from the trypanosome Crithidia fasciculata. A geometric model of the transition-state structure for the enzymatic hydrolysis of inosine by nucleoside hydrolase has been established by the analysis of a family of kinetic isotope effects [Horenstein, B.A., Parkin, D.W., Estupinan, B., & Schramm, V.L. (1991) Biochemistry 30, 10788]. The transition state has substantial oxycarbonium ion character, but the results of electrostatic potential calculations indicate that the transition-state charge is distributed over the ribosyl ring rather than existing as a localized C+-O<==>C = O+ resonance pair. The electrostatic potential surfaces of the substrate and enzyme-bound products differ considerably from that of the transition state. At the transition state both hypoxanthine and ribose demonstrate regions of positive charge. The positive charge on the ribosyl oxycarbonium ion is moderated by association with an enzyme-directed water nucleophile. The enzyme-bound products contain adjacent areas of negative charge. The electrostatic potential surfaces provide novel insights into transition-state structure and the forces causing release of products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343503 TI - Structures of thymidylate synthase with a C-terminal deletion: role of the C terminus in alignment of 2'-deoxyuridine 5'-monophosphate and 5,10 methylenetetrahydrofolate. AB - Thymidylate synthase undergoes a major conformational change upon ligand binding, where the carboxyl terminus displays the largest movement (approximately 4 A). This movement from an "open" unliganded state to the "closed" complexed conformation plays a crucial role in the correct orientation of substrates and in product formation. The mutant lacking the C-terminal valine (V316Am) of the enzyme is inactive. X-ray crystal structures of V316Am and its complexes with dUMP, FdUMP, and both FdUMP and CH2H4folate are described. The structures show that ligands are bound within the active site, but in different modes than those in analogous, wild-type thymidylate synthase structures. The 2.7-A binary complex structures of V316Am with FdUMP and dUMP show that the pyrimidine and ribose moieties of the nucleotides are pivoted approximately 20 degrees around the 3' hydroxyl compared to dUMP in the wild-type enzyme. The 2.7-A crystal structure of V316Am complexed with cofactor, CH2H4folate, and the substrate analog, FdUMP, shows these ligands bound in an open conformation similar to that of the unliganded enzyme. In this ternary complex, the imidazolidine ring of the cofactor is open and has reacted with water to form 5-HOCH2H4folate. 5 HOCH2H4folate is structural evidence for the 5-iminium ion intermediate, which is the proposed reactive form of CH2H4folate. The altered ligand binding modes observed in the three V316Am complex structures open new venues for the design of novel TS inhibitors. PMID- 8343504 TI - NMR solution structure of human parathyroid hormone(1-34). AB - The aqueous solution structure of the biologically-active N-terminal domain of human parathyroid hormone (residues 1-34) was studied by two-dimensional proton nuclear magnetic resonance (2D NMR) spectroscopy, distance geometry, and dynamic simulated annealing. Unambiguous NMR assignments of all backbone and side chain hydrogens were made with the aid of totally correlated spectroscopy experiments, which provided through-bond 1H-1H connectivities, and nuclear Overhauser effect spectroscopy, which provided through-space and sequential backbone connectivities. The NMR data acquired were utilized in a distance geometry algorithm to generate a family of structures which were then refined using dynamic simulated annealing. The major structural feature evident is alpha-helix extending from residues Glu4 to Lys13 and from Val21 to Gln29 with a turn incorporating Asn16-Glu19 resulting in a quite globular C-terminal domain with a hydrophobic core comprising Leu15, Leu18, Trp23, and Val31. Structure-activity studies are interpreted in terms of the deduced conformation of the PTH structure with particular reference to the likely PTH receptor binding site formed primarily by the bulk of the C-terminal helix. PMID- 8343505 TI - An elongated form of T4 glutaredoxin with four extra residues. AB - Two different forms of T4 glutaredoxin (thioredoxin) arising from the same gene on a multicopy plasmid in an Escherichia coli expression system have been isolated and characterized. Up to one-fourth of purified T4 glutaredoxin has an extension of four amino acids in the carboxy terminus, with the sequence aspartate, arginine, isoleucine, lysine. This four-residue extension may be caused by a translational +1 frameshift at the UGA terminator codon. PMID- 8343506 TI - Mode of formation and structural features of DNA-cationic liposome complexes used for transfection. AB - Complexes formed between cationic liposomes and nucleic acids represent a highly efficient vehicle for delivery of DNA and RNA molecules into a large variety of eukaryotic cells. By using fluorescence, gel electrophoresis, and metal-shadowing electron microscopy techniques, the factors that affect the, yet unclear, interactions between DNA and cationic liposomes as well as the structural features of the resulting complexes have been elucidated. A model is suggested according to which cationic liposomes bind initially to DNA molecules to form clusters of aggregated vesicles along the nucleic acids. At a critical liposome density, two processes occur, namely, DNA-induced membrane fusion, indicated by lipid mixing studies, and liposome-induced DNA collapse, pointed out by the marked cooperativity of the encapsulation processes, by their modulations by DNA condensing agents, and also by their conspicuous independence upon DNA length. The DNA collapse leads to the formation of condensed structures which can be completely encapsulated within the fused lipid bilayers in a fast, highly cooperative process since their exposed surface is substantially smaller than that of extended DNA molecules. The formation of the transfecting DNA-liposome complexes in which the nucleic acids are fully encapsulated within a positively charged lipid bilayer is proposed, consequently, to be dominated by mutual effects exerted by the DNA and the cationic liposomes, leading to interrelated lipid fusion and DNA collapse. PMID- 8343507 TI - Reorientation time of DNA molecules in pulsed-field gel electrophoresis. AB - The precise determination of the influence of an electric field strength E on the resolution of DNA molecules during a pulsed-field gel electrophoresis shows that the maximal molecular size Nmax of still resolved DNA molecules is described by the equation Nmax = k tau E alpha, where k is a coefficient, tau is a pulse time, and alpha is an exponent (calculated as approximately 3/2). We assume that the best estimation of the reorientation time tau R for each DNA fragment is such a pulse time in which this DNA molecule is the largest separated one. PMID- 8343508 TI - FT-IR studies on the triplet state of P680 in the photosystem II reaction center: triplet equilibrium within a chlorophyll dimer. AB - The structure and molecular interactions of the primary donor (P680) in the reaction center (D1-D2-cytochrome b-559 complex) of photosystem II (PS II) have been investigated by detecting light-induced FT-IR difference spectra upon the formation of its triplet state (3P680). The 3P680/P680 spectrum obtained was analyzed by comparing it with difference spectra between the ground and lowest triplet states of purified chlorophyll a (Chl) in organic solvents. The negative peaks at 1669 and 1707 cm-1 accompanied by the positive peaks at 1627 and 1659 cm 1 in the 3P680/P680 spectrum were assigned to the keto C = O stretching mode, and the appearance of these two pairs of bands indicated that P680 has a dimeric structure analogous to that of the bacterial primary donor. From the band positions of the keto and carbomethoxy C = O stretches, the hydrogen-bonding properties of these two Chl molecules were found to be asymmetrical; in one Chl molecule both the keto and carbomethoxy C = O groups form hydrogen bonds, while in the other Chl molecule the keto C = O is not hydrogen-bonded whereas the carbomethoxy C = O probably is hydrogen-bonded. The temperature dependence of the intensity ratios of the keto C = O bands revealed that the triplet state is equilibrated between the two Chl molecules with an energy gap of 8.4 +/- 0.7 meV. Most of the triplet population was found to be localized on one Chl molecule (86% at 80 K), in which both of the two C = O groups are hydrogen-bonded, that is probably attached to the D1 subunit. Considering the structure of the bacterial reaction center determined by X-ray crystallography and the sequence homology between the D1 and D2 subunits of PS II and the L and M subunits of bacteria, a model of the P680 structure and its interactions with apoproteins has been proposed. PMID- 8343509 TI - Resonance Raman and optical transient studies on the light-induced proton pump of bacteriorhodopsin reveal parallel photocycles. AB - The photocycle of bacteriorhodopsin (bR) was studied at ambient temperature in aqueous suspensions of purple membranes using time-resolved resonance Raman (RR) and optical transient spectroscopy (OTS). The samples were photolyzed, and the fractional concentrations of the retinylidene chromophore in its parent state, BR570, and in the intermediate states L550, M412, N560, and O640 were determined in the time domain 20 microseconds-1 s and in the pH range 4-10.5. Two kinetically different L components could be identified. At pH 7 one fraction of L (approximately 65%) decays in 80 microseconds to M (deprotonation of the Schiff base), whereas the residual part is converted in approximately 0.5 ms to N. The RR spectra reveal only minor structural changes of the chromophore in the L-->N transition. These were attributed to a conformational change of the protein backbone [Ormos, P., Chu, K., & Mourant, J. (1992) Biochemistry 31, 6933]. With decreasing pH the L-->N transition is delayed to > 2 ms following a titration like function with pKa approximately 6.2. The decay of M412 monitored by OTS can be fitted for each pH value by two different amplitudes and time constants (Mf, tau f; Ms, tau s; f = fast, s = slow). Both Mf and Ms consist of subcomponents which can be distinguished by their different reaction pathways (but not by OTS). Mf occurs in the reaction sequences L-->Mf-->N-->BR and L-->Mf-->O-->BR. The population of the first sequence, in which N is formed with the time constant tau f (approximately 2-4 ms, pH 6-10.5), increases with pH. Ms is also found in two different reaction sequences of the form L-->Ms-->BR. The quantitative analysis reveals that each "titration effect" can be related to a certain fraction of bR. It is proposed that each fraction can be identified with a "subspecies" of bR which undergoes an independent and individual cyclic reaction. A complete reaction scheme is set up which represents the manifold of observed phenomena. It is concluded from the pH dependence of the lifetimes of Ms and N that the reconstitution of BR570 in the reaction steps Ms-->BR and N-->BR requires the uptake of a proton from the external phase. It is argued that this proton catalyzes the reisomerization of retinal, whereas the Schiff base is internally reprotonated from Asp-85. A model for proton pumping is proposed in which the proton taken up from the external phase to catalyze the reisomerization of retinal is the one which is pumped through the membrane during the photocycle of bR. PMID- 8343510 TI - Characterization of hemopexin and its interaction with heme by differential scanning calorimetry and circular dichroism. AB - Hemopexin is a plasma glycoprotein that has two structural domains (I and II) and binds and transports heme particularly to liver cells. Differential scanning calorimetry (DSC) studies show that hemopexin is largely stabilized by heme, which binds exclusively to domain I. The melting temperature (Tm) of heme hemopexin is 66.4 +/- 0.7 degrees C as compared with 53.9 +/- 0.3 degrees C for apohemopexin, and this Tm increase is accompanied by a 100 kcal increase in molar enthalpy. Heme stabilizes hemopexin by stabilizing domain I. This is demonstrated by the 26 degrees C increase in Tm from 51.9 +/- 0.3 to 77.6 +/- 0.6 degrees C and the over 3-fold increase in molar enthalpy when domain I associates with heme. A moderate change in domain I secondary structure is indicated by an increase in negative molar ellipticity at 206 nm. However, there is no net effect on the secondary structure of holo-hemopexin caused by heme binding as indicated by both far-UV circular dichroism (CD) and Fourier-transform infrared spectra. The characteristic positive ellipticity of hemopexin at 233 nm, ascribed to tryptophan residues in domain II, is dramatically increased, suggesting a change in teritary structure for domain II of hemopexin. DSC and CD results show that isolated domain I and domain II interact both in the presence and absence of heme. Moreover, domain II destabilizes heme-domain I, which may be an important factor in facilitating heme release to the hemopexin receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343511 TI - The Schiff base bond configuration in bacteriorhodopsin and in model compounds. AB - The Schiff base linkage bond configuration of bacteriorhodopsin was studied using model compounds consisting of all-trans- and 13-cis-retinal-protonated Schiff bases bearing C = N anti and syn bond configurations. The C = N configuration was analyzed using a combination of Fourier transform infrared spectroscopy and isotopically labeled chromophores. It was found that, in the model compounds, the coupling between the C14--C15 stretching frequency and the N--H rock is weak in the all-trans-retinal-protonated Schiff base in both the anti and syn C = N configurations. However, this coupling is relatively strong in the 13-cis-retinal protonated Schiff base in both the anti and syn C = N configurations. Thus, it is concluded that, in model compounds, the C14--C15 mode can serve as a marker for the C13 = C14 bond configuration but not for the C = N. A different situation may prevail in bacteriorhodopsin due to different conformations of the retinal chromophore in the protein binding site and in solution. This difference suggests that the C14--C15/NH coupling in retinal-protonated Schiff bases is affected by the retinal conformation. PMID- 8343512 TI - Regulation of the rhodopsin-transducin interaction by a highly conserved carboxylic acid group. AB - Rhodopsin is a member of a family of G protein-coupled receptors which share structural and functional homologies. A tripeptide sequence (Glu or Asp/Arg/Tyr) at the cytoplasmic border of the third transmembrane segment is conserved among most of these receptors. This region is involved in G protein activation in rhodopsin as well as in other receptors. The role of the conserved Glu-134 was studied by site-specific mutagenesis of rhodopsin in combination with a real-time fluorescence assay of G protein (transducin) activation. Assay conditions were chosen under which the transducin activation rate was determined either by rhodopsin-transducin complex formation or by GTP gamma S-induced complex dissociation. Glu-134 was replaced by Gln in order to mimic the protonated state of the carboxylic acid group. This mutation caused the pH dependency of complex formation to extend to the alkaline range as compared with rhodopsin. Replacement of Glu-134 by Asp had an opposite but less pronounced effect on the pH dependency and lowered the overall efficiency of transducin activation. The acidity constant (pKa) of the residue at position 134 did not directly determine the pH sensitivity of complex formation, indicating that other amino acid residues contribute to a titratable binding domain that includes Glu-134. In contrast, the pH sensitivity of GTP gamma S-induced complex dissociation was not changed by the mutations, although absolute rates were affected. The data suggest that the protonated state of Glu-134 favors binding of rhodopsin to transducin and that Glu-134 is not titratable in the rhodopsin-transducin complex. PMID- 8343513 TI - Importance of main-chain flexibility and the insulin fold in insulin-receptor interactions. AB - We have investigated the effects of altering the disposition between the COOH terminal B chain domain of insulin and the core of the insulin molecule on ligand interactions with the hepatocyte insulin receptor. Analogues include those in which ArgB22 of des-octapeptide(B23-B30)-insulin is extended by one to three residues of glycine prior to termination in Phe-NH2, by one to five residues of glycine prior to termination in Phe-Phe-NH2, or by an additional residue of glycine prior to termination in more extended sequences derived from insulin or [GlyB24]insulin. Analogues were also examined with respect to their abilities to form hexamers in solution in the presence of Co2+, phenol, and NaSCN. Overall, our studies of ligand-receptor interactions identify that (a) the energetic penalty for the introduction of a single residue of glycine is uniform in all classes of analogues for up to three residues of glycine but diminishes somewhat for analogues with longer insertions and (b) the COOH-terminal residues of the B chain retain their importance for all classes of analogues, no matter the number of glycine residues introduced. Analogues with glycine insertions, but not those with glycine substitutions, readily form thiocyanate-stabilized complexes with Co2+ in the presence of phenol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343514 TI - A structural and kinetic study on myofibrils prevented from shortening by chemical cross-linking. AB - In previous work, we studied the early steps of the Mg(2+)-ATPase activity of Ca(2+)-activated myofibrils [Houadjeto, M., Travers, F., & Barman, T. (1992) Biochemistry 31, 1564-1569]. The myofibrils were free to contract, and the results obtained refer to the ATPase cycle of myofibrils contracting with no external load. Here we studied the ATPase of myofibrils contracting isometrically. To prevent shortening, we cross-linked them with 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide (EDC). SDS-PAGE and Western blot analyses showed that the myosin rods were extensively cross-linked and that 8% of the myosin heads were cross-linked to the thin filament. The transient kinetics of the cross-linked myofibrils were studied in 0.1 M potassium acetate, pH 7.4 and 4 degrees C, by the rapid-flow quench method. The ATP binding steps were studied by the cold ATP chase and the cleavage and release of products steps by the Pi burst method. In Pi burst experiments, the sizes of the bursts were equal within experimental error to the ATPase site concentrations (as determined by the cold ATP chase methods) for both cross-linked (isometric) and un-cross-linked (isotonic) myofibrils. This shows that in both cases the rate-limiting step is after the cleavage of ATP. When cross-linked, the kcat of Ca(2+)-activated myofibrils was reduced from 1.7 to 0.8 s-1. This is consistent with the observation that fibers shortening at moderate velocity have a higher ATPase activity than isometric fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343515 TI - Modification of oligosaccharide antenna flexibility induced by exoglycosidase trimming. AB - We have investigated the solution conformation of a triantennary glycopeptide using resonance energy transfer [Rice et al. (1991) Biochemistry 30, 6646-6655]. Triantennary glycopeptide was derivatized with a donor fluorophore on the N terminus and with an acceptor fluorophore attached individually to each terminal galactose residue, resulting in three isomeric donor-acceptor pairs. Time resolved energy-transfer experiments revealed two distinct donor-acceptor distance populations for two of the three antennae of the oligosaccharide. An extended conformation and a folded conformation were detected for the two flexible antennae whereas the third antenna on the oligosaccharide was rigid, containing only an extended conformer. The ratios of the extended to folded conformers of the two flexible antennae were reversibly modulated by temperature, allowing the calculation of delta H and delta S for the conformational change [Wu et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 9355-9359]. In the present study, we have trimmed the fluorescent glycopeptides with exoglycosidases which specifically removed the unmodified antennae of the oligosaccharide. The resulting single-chain isomeric glycopeptides each contained identical core sugar residues and a terminally located donor and acceptor, but differed only in the linkage configuration of the sugar residues. Analysis of these glycopeptides by time-resolved energy transfer indicated that each antenna of the oligosaccharide is, by itself, maintained exclusively in the extended conformation. Temperature modulation failed to induce antenna folding as was previously observed for the complete triantennary structure. These data suggest that interantenna interactions modulate the conformation of individual antenna of complex oligosaccharides. PMID- 8343516 TI - Purification of human thioredoxin reductase: properties and characterization by absorption and circular dichroism spectroscopy. AB - The flavoenzyme thioredoxin reductase (TR) and its natural substrate thioredoxin comprise a redox system generally found in all organisms. In order to better understand the biochemistry of this redox system, TR was purified (> 4000-fold) from human placenta as a dimer of 60-kDa subunits. The molecular size of native TR was determined to be 160 kDa by gel filtration chromatography whereas migration on a sucrose gradient gave a molecular mass of 130 kDa. The pI of TR was determined to be 4.85. The temperature optima for DTNB and insulin reduction by TR were 52 and 40 degrees C, respectively. Preincubation of TR at 60 degrees C for up to 1 h showed no decrease in the enzymatic rates when assayed at 28 degrees C, while temperatures above 65 degrees C resulted in an irreversible loss of activity. Circular dichroism (CD) spectra of TR indicated that the secondary structural changes at 60 degrees C were only partly reversible at 28 degrees C. CD studies showed the flavoenzyme had a TM of 63 degrees C and above 45 degrees C began to exhibit changes in the secondary structure. Equilibrium denaturation of TR by temperature and guanidine hydrochloride suggested that FAD was not displaced during inactivation of TR and that the tertiary structure was primarily disrupted prior to denaturation of the secondary structure. The results of this study show that purified human TR is a relatively thermostable flavoenzyme whose tightly bound FAD group is not displaced by elevated temperatures up to 60 degrees C or by relatively low concentrations of guanidine hydrochloride. PMID- 8343517 TI - A new kinetic mechanism for the concomitant hydrolysis and transfer reactions catalyzed by bacterial DD-peptidases. AB - In the presence of an adequate nucleophilic acceptor substrate (A) and ester and thiolester donor substrates (S), the Streptomyces R61 soluble DD-peptidase catalyzes both hydrolysis and acyl group transfer reactions. Simple bisubstrate models do not explain the variation of the transfer to hydrolysis ratios with the donor and acceptor concentrations. A new kinetic mechanism for the concomitant hydrolysis and transfer reactions is proposed which involves an acceptor and a second, nonproductive donor substrate binding site. In this model, the acceptor essentially binds to the acyl-enzyme, and the second donor molecule only binds to the ternary ES*A complex. Hydrolysis can then proceed from the quaternary ES*AS complex. The values of all of the parameters involved in the reaction of a thiolester substrate with D-alanine as the acceptor substrate were determined at 15 and 37 degrees C. The results obtained with a protein modified by site directed mutagenesis, and with which the transpeptidation reaction appeared to be specifically impeded, are discussed on the basis of the new kinetic mechanism. The data obtained with the soluble form of the high molecular weight penicillin binding protein 2X from Streptococcus pneumoniae are also in agreement with this model. PMID- 8343518 TI - Heparin binding affinity of normal and genetically modified antithrombin III measured using a monoclonal antibody to the heparin binding site of antithrombin III. AB - The inhibitory activity of the plasma serine proteinase inhibitor antithrombin III (AT III) is enhanced about 1000-fold upon binding to heparin. We have determined the dissociation constants, Kd, of 48.8 nM for the heparin-AT III interaction, of 175 nM for the specific pentasaccharide-AT III interaction, and of 13 microM for the low-affinity heparin-AT III interaction, using a binding assay based on a monoclonal antibody (MAb) that recognizes an epitope at or close to the heparin binding site of AT III. The heparin binding affinities and proportions of normal and variant AT III in plasma from patients with mutations of AT III have been quantitated for the first time using the binding assay. Substitution mutations in three regions of AT III have been investigated: (i) mutations in the reactive site loop affecting Ala382, Arg393, and Ser394 have no discernible effect on heparin binding; (ii) mutations in the previously identified N-terminal heparin binding region, affecting Arg47, Leu99, and Arg129, produce variant AT III molecules with heparin affinities reduced 11-924-fold, the largest reduction being observed for the substitution mutation Arg47-Cys in Padua 2, which has an affinity of 65.6 microM; (iii) mutations in the hydrophobic regions around strand 1C of the C terminus, affecting Phe402, Ala404, Asn405, Pro407, and Pro429, have pleiotropic effects that include the production of reduced amounts of low-affinity AT III with dissociation constants from 6 to 43 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343519 TI - Distinct metal binding configurations in ACE1. AB - The ACE1 protein of Saccharomyces cerevisiae mediates the metal-induced expression of the CUP1 metallothionein (MT) genes. Curiously, ACE1 resembles the MT protein in the types of metal complexes that form. ACE1 binds Cd(II) and Cu(I) ions in distinct configurations, but only the Cu(I) conformer of ACE1 forms a high-affinity and specific complex with DNA. Cu(I) ions associated with ACE1 are known to assemble in a polymetallic CuI-thiolate cluster that resembles Cu metallothionein in metal coordination properties [Dameron, C. T., Winge, D. R., George, G. N., Sansone, M., Hu, S., & Hamer, D. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6127-6131]. In contrast to the Cu(I) nuclearity of 6-7 mol equiv in ACE1 and 7 mol equiv in yeast MT, divalent ions, including Cd(II), Zn(II) and Co(II), bind with a maximal stoichiometry of near 4 mol equiv in ACE1 and 4 mol equiv in yeast MT. Charge-transfer bands consistent with metal:thiolate coordination were observed in CdACE1 and CoACE1. Spectroscopic studies of CoIIACE1 and EXAFS analysis of CdIIACE1 revealed tetrahedral coordination geometry in these complexes. Similar tetrahedral coordination complexes were observed with Co(II) and Cd(II) complexes of MT from S. cerevisiae. Metal binding in ACE1 is clearly similar to that in MT, and therefore the MT-metal clusters appear to be a good structural model of the metal center of ACE1. PMID- 8343520 TI - Thermodynamics of ligand binding to trp repressor. AB - The thermodynamics of L-tryptophan and operator DNA binding to the tryptophan repressor of Escherichia coli were analyzed by titration microcalorimetry and van't Hoff analysis of footprinting titrations, respectively. At 25 degrees C in 10 mM sodium phosphate, pH 7.6, and 0.1 M NaCl, the binding of L-tryptophan to the repressor is characterized by values of delta G degrees = -6.04, delta H degree = -14.7, and T delta S degree = -8.67 kcal/mol. The temperature dependence of delta H degree yields delta Cp degree = -0.46 +/- 0.08 kcal/(mol.K) per dimer. The binding is noncooperative at all temperatures studied. At 23 degrees C in 2.5 mM sodium phosphate, pH 7.6, and 25 mM NaCl, the binding of operator DNA to the repressor is characterized by values of delta G degree = -13.3 kcal/mol, delta H degree = -1.55 kcal/mol, T delta S degree = 11.8 kcal/mol, and delta Cp degree = 0.54 +/- 0.10 kcal/(mol.K). Changes in water-accessible surface areas upon binding of L-tryptophan or DNA were calculated from X-ray crystal structures. The experimentally observed delta Cp degree values were compared with delta Cp degree values calculated according to several methods based on various proposed relationships between surface area changes and heat capacity changes. Regardless of which method is used, we find poor agreement between the calorimetric results for L-tryptophan binding and the surface areas calculated from X-ray data; the direction of the discrepancy is that the X-ray data underestimate the value of delta Cp degree.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343521 TI - Intramolecular electron transfer in single-site-mutated azurins. AB - Single-site mutants of the blue, single-copper protein, azurin, from Pseudomonas aeruginosa were reduced by CO2- radicals in pulse radiolysis experiments. The single disulfide group was reduced directly by CO2- with rates similar to those of the native protein [Farver, O., & Pecht, I. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6968-6972]. The RSSR- radical produced in the above reaction was reoxidized in a slower intramolecular electron-transfer process (30-70 s-1 at 298 K) concomitant with a further reduction of the Cu(II) ion. The temperature dependence of the latter rates was determined and used to derive information on the possible effects of the mutations. The substitution of residue Phe114, situated on the opposite side of Cu relative to the disulfide, by Ala resulted in a rate increase by a factor of almost 2. By assuming that this effect is only due to an increase in driving force, lambda = 135 kJ mol-1 for the reorganization energy was derived. When Trp48, situated midway between the donor and the acceptor, was replaced by Leu or Met, only a small change in the rate of intramolecular electron transfer was observed, indicating that the aromatic residue in this position is apparently only marginally involved in electron transfer in wild-type azurin. Pathway calculations also suggest that a longer, through-backbone path is more efficient than the shorter one involving Trp48. The former pathway yields an exponential decay factor, beta, of 6.6 nm-1. Another mutation, raising the electron-transfer driving force, was produced by changing the Cu ligand Met121 to Leu, which increases the reduction potential by 100 mV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343522 TI - The properties of the secreted gamma-glutamyl hydrolases from H35 hepatoma cells. AB - gamma-Glutamyl hydrolase has been partially purified and characterized from conditioned culture medium of H35 hepatoma cells. Evidence for heterogeneity of the enzyme is derived from its elution as three distinct peaks of enzymatic activity when the enzyme is purified by TSK-butyl-Sepharose column chromatography. These three enzyme fractions appear to have identical catalytic properties but, as yet, the basis for their resolution is not understood. A rapid, sensitive and simple assay based on reverse-phase HPLC fluorescent detection with pre-column derivatization using o-phthalaldehyde (OPA) was developed to separate OPA-derivatives of poly-gamma-glutamates and glutamic acid. Using this assay and the standard HPLC assay for pteroylpolyglutamates, the enzyme appears to be an endopeptidase with respect to pteroylpenta-gamma glutamate (PteGlu5), methotrexate penta-gamma-glutamate (4-NH2-10-CH3PteGlu5) and p-aminobenzoyl-penta-gamma-glutamate (pABAGlu5). The initial products are PteGlu1 (or 4-NH2-10-CH3PteGlu1 or pABAGlu1) and intact tetra-gamma-glutamate, which is subsequently degraded to glutamic acid. When penta-gamma-glutamate is the substrate, the cleavage of the gamma-bonds by the enzyme is less ordered, with the early appearance of mono-, di-, tri- and tetraglutamate. Poly-alpha-glutamate is not a substrate nor are pABA-gamma-Glu5 or penta-gamma-glutamate covalently linked to albumin. 4-NH2-10-CH3PteGlu2 or Glu5 bound to dihydrofolate reductase is not a substrate for the enzyme, offering further evidence that protein associated poly-gamma-glutamates are poor substrates for gamma-glutamyl hydrolase from H35 hepatoma cells. PMID- 8343524 TI - AMP-deaminase from human uterine smooth muscle: the effect of DTNB treatment on kinetic and regulatory properties of the enzyme. AB - Reactivity of sulfhydryl groups of human uterine smooth muscle AMP-deaminase with DTNB, and the effect of their chemical modification on kinetic and regulatory properties of the enzyme were investigated. (1), Approx. 7 and 5 sulfhydryl groups per mol of the enzyme have been shown to be accessible for DTNB (5,5' dithiobis(2-nitrobenzoic acid)) titration in denaturated and native AMP deaminase, respectively. (2), Titrated groups were not homogenous; some of them reacted with DTNB much faster than others. (3), The activity of the modified enzyme was very low, and the modified enzyme manifested unusual hyperbolic saturation kinetics with the substrate. (4), Exhaustive dialysis against a buffer containing 10 mM thioethanol reactivated the modified enzyme, and restored its original regulatory properties. Experimental results obtained indicate that modified sulfhydryl groups play a significant role in the maintenance of the proper, catalytically-efficient conformation of the enzyme. PMID- 8343523 TI - Local variations in protein structure in the human eye lens: a Raman microspectroscopic study. AB - Confocal Raman microspectroscopy was used to monitor local and age-related changes in protein conformation in human eye lenses. In clear human lenses of varying age (range 17-80 years) spectra were recorded along the visual axis, using laser light of 660 nm wavelength. The Raman vibrations in the 650-1750 cm-1 spectral region were analyzed. Difference spectra between central core and different positions along the visual axis were calculated after calibration for protein content using the I(1450) cm-1 CH2/CH3 vibration peak. Tryptophan content was quantified using the peak at 760 cm-1 calibrated for protein. Changes in the 'exposed' vs. 'buried' position of tryptophan were analyzed using the peak heights at I(880) and I(760) cm-1. The difference spectra revealed an excess of tryptophan, tyrosine, phenylalanine, beta-sheet conformation and molecules or molecular groups responsible for a 1425 cm-1 peak in the core region in all lenses investigated. The excess peaks disappeared at about 0.6-0.9 mm below the surface. The tryptophan content increased from superficial to deep layers, levelling off between 0.4-0.8 mm below the surface. Upon aging, the tryptophan content increases in the core not in the cortex. No changes in the 'exposed' vs. 'buried' position of tryptophan were observed. Changes in tryptophan and tyrosine probably reflect the maturational shift from cortex to core in the relative content of alpha, beta and gamma crystallines. The age-related increase in tryptophan in the core may reflect the preferential breakdown by endo- and exopeptidases of alpha-crystallins damaged upon aging. The increase in beta-sheet conformation may indicate a post-translational shift in secondary conformation upon aging. These changes in protein conformation are largely completed in a small superficial zone, i.e., in the early life span of the crystallins. PMID- 8343525 TI - Identification of the reactive cysteine residue in human placenta aldose reductase. AB - Modification of human placental aldose reductase by iodoacetate (IAA) led to a mol/mol binding of IAA, a 40% decrease in the kcat, a 3-5-fold increase in the Km,NADPH and Km,glyceraldehyde and a 600-fold increase in the Ki,sorbinil; determined at pH 6.0. NADPH and 2'-monophosphoadenosine 5'-diphosphoribose but neither glyceraldehyde nor sorbinil, prevented carboxymethylation-induced changes. Cleavage of [14C]IAA-modified enzyme by trypsin resulted in two radiolabeled peptides: Val-297 to Lys-307 and Val-297 to Phe-315. In both these peptides Cys-298 was the only radiolabeled residue. It is suggested that Cys-298 regulates the kinetic and inhibition properties of the enzyme, but does not participate in catalysis. PMID- 8343526 TI - Comparison of acyl-carrier protein and other protein structures in aqueous solutions by Fourier-transform infrared spectroscopy. AB - Protein solution structures were analyzed by horizontal attenuated total reflectance (ATR) FTIR spectroscopy. Secondary structure compositions determined from analyses of amide-I and II region and amide-III region difference spectra were compared. Data for proteins of known solution structure, cytochrome c, concanavalin A and lysozyme, were compared with those reported in the literature. Melittin, a peptide from bee venom whose secondary structural configuration varies depending upon solution conditions was also examined. Acyl-carrier protein (ACP) is a small protein of recognized dynamic structure that in its diverse physiologic roles interacts specifically with numerous different proteins. Horizontal ATR FTIR analysis of ACP's secondary structure indicated a predominantly helical structure best defined as a combination of ordered and disordered helices. The FTIR-derived structural composition agreed with those determined for ACP by other techniques. Comparison of independent analyses of the amide-I and III regions to determine protein configuration compositions was a useful method of verifying the internal consistency of the calculated structural compositions of dynamically-structured proteins. PMID- 8343527 TI - 3-(Alkylthio)-N-hydroxysuccinimide derivatives: potent inhibitors of human leukocyte elastase. AB - A series of 3-(alkylthio)-N-hydroxysuccinimide derivatives was synthesized and their inhibitory activity towards human leukocyte elastase (HLE) was investigated. The interaction of the compounds having a 3-alkylthioether side chain (compounds 1 and 2) with HLE was found to involve rapid acylation of the enzyme, followed by total regain of enzymatic activity within 3 h. Interestingly, compounds 3-8, having an oxidized thioether side chain, were found to be highly effective, time-dependent, irreversible inhibitors of the enzyme. The k(obs)/I values for compounds 3-8 ranged between 890 and 24,000 M-1 s-1. These findings demonstrate that, unlike the physiological inhibitor of HLE (alpha-1-proteinase inhibitor), which is inactivated upon oxidation, low-molecular-weight compounds retain and/or show enhanced inhibitory activity towards HLE upon oxidation of the thioether side chain and lay the groundwork for the development of compounds that embody proteinase inhibitory and antioxidant activity. PMID- 8343528 TI - Thiols, gold-thiols, zinc-thiols and the redox state of hemoglobin. AB - The beta subunit of human hemoglobin can be oxidized site-specifically through beta-Cys-93 by Cu(II)(His)2. A series of thiol ligands, gold thiols and zinc(II) inhibit this oxidation. The thiol inhibitors formed a transient ternary intermediate involving Cu(I) with consequent inhibition of electron transfer from the Fe(II)-heme. The intermediate led to the formation of a disulfide at the beta Cys-93 site. The most effective thiols achieved maximum inhibition at one equivalent per beta heme. Gold thiols and zinc complexes inhibited heme oxidation by competing with the Cu(II)(His)2 for the beta-Cys-93 site. PMID- 8343529 TI - Identity and some properties of the L-threonine aldolase activity manifested by pure 2-amino-3-ketobutyrate ligase of Escherichia coli. AB - 2-Amino-3-ketobutyrate ligase catalyzes the reversible, pyridoxal 5'-phosphate dependent condensation of glycine with acetyl CoA forming the unstable intermediate, 2-amino-3-ketobutyrate. Several independent lines of evidence indicate that the pure protein obtained in the purification of this ligase from Escherichia coli also has L-threonine aldolase activity. The evidence includes: (a), a constant ratio of specific activities (aldolase/ligase) at all stages of purifying 2-amino-3-ketobutyrate ligase to homogeneity; (b), the same rate of loss of aldolase and ligase activities during controlled heat inactivation of the pure protein at 60 degrees C in the absence, as well as in the presence of acetyl CoA, a protective substrate; (c), ratios of the two enzymatic activities that are not significantly different during slow inactivation by iodoacetamide, with and without L-threonine added; (d), coincident rates of loss and essentially identical rates of recovery of aldolase activity and ligase activity during resolution of the holoenzyme with hydroxylamine followed by reconstitution with pyridoxal 5'-phosphate. No aldolase activity is observed with D-threonine as substrate and L-allothreonine is about 25% as effective as L-threonine. Whereas ligase activity has a sharp pH optimum at 7.5, the aldolase activity of this pure protein is maximal at pH 9.0. Comparative apparent Km values for glycine (ligase) and L-threonine (aldolase) are 10 mM and 0.9 mM, respectively, whereas corresponding respective Vmax values were found to be 2.5 mumol of CoA released/min per mg vs. 0.014 mumol of acetaldehyde formed (NADH oxidized)/min per mg. PMID- 8343530 TI - Purification and properties of a flavodoxin from the heterocystous cyanobacterium Anabaena sphaerica. AB - A flavodoxin was purified to homogeneity from the nitrogen-fixing heterocystous cyanobacterium Anabaena sphaerica grown under iron-limited conditions. The protein has a molecular mass of 21 kDa, and its spectral properties and amino acid composition are very close to that of flavodoxins from other cyanobacteria. A. sphaerica flavodoxin supported the activities of A. sphaerica NADP reductase and Clostridium butyricum hydrogenase in reconstituted systems with illuminated plant chloroplasts as reductant. With the use of polyclonal anti-flavodoxin antiserum it was found that nitrogen-fixing cultures of A. sphaerica grown under iron-sufficient conditions contain low but significant amounts of flavodoxin (0.2 0.6 micrograms/mg crude extract protein) which increased dramatically (to 8-15 micrograms/mg crude extract protein) after the iron concentration in the medium was decreased to below 1 microM Fe. The flavodoxin content of both iron-limited and iron-sufficient. A. sphaerica was also shown to depend upon the growth phase of the (batch) cultures with a maximum at early exponential phase, coinciding with maximal in-vivo nitrogenase activity. These results suggest that A. sphaerica flavodoxin not only substitutes for ferredoxin under iron-limiting conditions, but also fulfills some specific role under iron-sufficient conditions. PMID- 8343531 TI - The in-vivo identification of the MoFe protein (FeMo cofactor) of nitrogenase in Klebsiella pneumoniae and of the Mo-storage protein in Azotobacter vinelandii via the nuclear quadrupole interaction of 99Mo(beta-)99Tc. AB - The expression of the MoFe protein of nitrogenase in Klebsiella pneumoniae was identified in vivo via the nuclear quadrupole interaction (NQI) of 99Mo(beta )99Tc using perturbed angular correlations of gamma-rays. The NQI parameters were: omega approx. 360 Mrad/s and eta approx. 1. In addition, the NQI of the 'Mo storage protein' in Azotobacter vinelandii cells which had been grown in the presence of NH4+ (13 mM), i.e. under conditions of strict repression of nitrogenase synthesis, was determined: omega approx. 190 Mrad/s, eta approx. 0.25. Under these conditions, the characteristic signal of the MoFe protein (FeMo cofactor) was absent. PMID- 8343532 TI - Fluorometric analysis of native, urea-denatured and refolded human prostatic acid phosphatase. AB - Human prostatic acid phosphatase (EC 3.1.3.2) was denatured in 6 M urea at pH 2.5, but was refolded by dilution at pH 7.0, as demonstrated by the recovery of nearly complete enzyme activity and dimeric structure. The conformational changes among the native, denatured and refolded states were monitored by means of steady state and nanosecond pulse fluorometry of tryptophan residues of the enzyme. The relative quantum yield of the fluorescence was highest in the native enzyme and lowest in the denatured one, and was intermediate in the refolded enzyme, although the emission peak was reproducible after refolding. The observed decay curves of tryptophan fluorescence of the native, denatured and refolded states were analyzed by decay functions of three lifetimes. The fluorescence lifetimes of the refolded enzyme were shorter than those of the native one. The fluorescence of the denatured enzyme decayed much faster than that of the other forms. The fluorescence excitation spectra revealed that the excitation energy of phenylalanine was transferred to tryptophan(s) in the native and refolded forms, but not in the denatured form. The efficiency of the energy transfer was higher in the native enzyme than in the refolded one. It was found by excitation polarization spectra that the freedom of internal motion of tryptophans was greater in the refolded enzyme than in the native enzyme. In the denatured enzyme the polarization anisotropies were very low. These results indicate that the higher structure with respect to tryptophans of the refolded enzyme is delicately but definitely different from that of the native enzyme and that local conformation of the active center is recovered upon refolding. PMID- 8343533 TI - Purification and immunohistochemical tissue localization of human xanthine oxidase. AB - Xanthine oxidase was purified 1600-fold from human liver cytosol. The purified enzyme was shown as a single band of 300 kDa on polyacrylamide gel electrophoresis and 150 kDa on SDS-PAGE. Using this purified enzyme, polyclonal antibody against xanthine oxidase was raised in a rabbit. On Ouchterlony's double immunodiffusion method, the raised antibody and the human liver cytosol made a precipitation line stained by activity stain and protein stain, respectively. With the raised anti-xanthine oxidase sera, the immunohistochemical localization of xanthine oxidase in human tissues was examined. Immunostaining of frozen hepatic tissue section showed that the cytoplasm of hepatocytes and endothelial lining cells were stained. In a number of other tissues, the xanthine oxidase antigen was detected only in the endothelial lining cells from heart, kidney, brain, aorta, lung and mesentery, except for the duodenal mucosa cells. A possible role for xanthine oxidase in the endothelial cells from various human tissues in the pathogenesis of reperfusion injury was suggested. PMID- 8343534 TI - Nucleation of the iron core occurs at the three-fold channels of horse spleen apoferritin: an EXAFS study on the native and chemically-modified protein. AB - Extended X-ray absorbance fine structure measurements have been carried out on the initial Fe(III)-apoferritin complex at a Fe/subunit ratio of 2 in native and modified horse spleen apoferritin. Analysis of the data indicates that in the native protein the iron forms a protein-bound polynuclear cluster (Fe-Fe distance 3.4 A) with a first coordination sphere constituted by 5-6 low-Z atoms, e.g., nitrogen atoms, carboxylate-like ligands or oxo bridges between the iron atoms. Modification of Cys-126, a residue localized on the outer surface of the hydrophilic three-fold channels, with p-chloromercuribenzoate (PMB) or phenylmercuric acetate (PMA) brings about distinctive differences. In particular, in the PMB-reacted protein the feature assigned to the iron-iron interaction disappears from the spectrum, whilst in the PMA-reacted protein the main differences with respect to the native protein are observed at the level of the first coordination sphere. These results confirm the formation of protein-Fe(III) clusters and localize these sites at the hydrophilic three-fold channels of horse spleen apoferritin. PMID- 8343535 TI - Lipoprotein lipase gene expression: physiological regulators at the transcriptional and post-transcriptional level. PMID- 8343536 TI - Dietary polyunsaturated fats suppress the high-sucrose-induced increase of rat liver pyruvate dehydrogenase levels. AB - Pyruvate dehydrogenase complex (PDC) has a key role in the regulation of hepatic lipogenesis by dietary factors. We have investigated the effects of dietary carbohydrate and fat on hepatic PDC. Sucrose-based or starch-based diets were administered for 15 days. A positive correlation between PDC activity and the lipogenic potential of the diet was found. A high-sucrose, fat-free diet caused a 3-fold increase in total activity whereas a high-starch, fat-free diet caused a 1.5-fold increase, as compared with chow-fed rats. Dietary polyunsaturated fat (PUF) caused a marked inhibitory effect on total and active PDC; fish oil being more effective than corn oil. Dietary saturated fat (butter) failed to inhibit the sucrose-induced elevation in total activity, but was almost as effective as fish oil in depressing percent active enzyme. Changes in total PDC activity closely correlated with modifications in the content of enzyme quantitated by immunoblotting, indicating that increased enzyme content and not activation is the predominant mechanism underlying the adaptive response to high-sucrose feeding. This response is suppressed by dietary PUF. Inhibition of hepatic lipogenesis by PUF involves a reduction of PDC content as well as that of several lipogenic enzymes. The relevant mechanisms remain to be established. PMID- 8343537 TI - Biosynthesis of a novel 3-oxo-2-tetradecyloctadecanoate-containing phospholipid by a cell-free extract of Corynebacterium diphtheriae. AB - We have isolated, purified, and identified by chemical analyses and mass spectrometry, a novel 3-oxo-2-tetradecyloctadecanoate (dehydrocorynomycolate) containing phospholipid (PL-1) from the chloroform-methanol extract of Corynebacterium diphtheriae. This phospholipid was separated from all of the other known dehydrocorynomycolate and 3-hydroxy-2-tetradecyloctadecanoate (corynomycolate)-containing lipids and found to be unstable even at -20 degrees C. It was present in trace amounts as a homologous series (molecular weights of 1400 and 1404 as the methyl esters) and composed of a dehydrocorynomycolate, a phosphate group, a diacylglycerol, and an unidentified amine-containing component. Because of the complexity of these phospholipids, their complete structural determination is yet to be completed. A cell-free extract of C. diphtheriae catalyzed the incorporation of radiolabel from [14C]palmitic acid into PL-1. This incorporation was ATP-dependent, and the rate was linear with respect to both time and protein concentration. The radiolabel was incorporated primarily into the dehydrocorynomycoloyl moiety of PL-1. While avidin did not show any significant effect, cerulenin showed a marked inhibition of this reaction. Based on these results, we suggest that this dehydrocorynomycolate containing PL-1 may be the long-sought acyl carrier-containing product of a Claisen-type condensation. PMID- 8343538 TI - Exposure of rabbit fetal lung to glucocorticoids in vitro does not enhance transcription of the gene encoding pulmonary surfactant-associated protein-B (SP B). AB - We have investigated the ontogeny and hormonal regulation of both synthesis rates and cellular accumulation of the mRNA for surfactant-associated protein B (SP-B) in rabbit fetal lung. The developmental pattern for SP-B mRNA synthesis increased as a function of gestational age and paralleled that for SP-B mRNA levels except on days 22-26 of gestation where relatively higher levels of gene transcription were observed. Time-course studies with explants from 26- and 30-day fetal lung maintained in culture revealed a gradual increase in mRNA levels and a much smaller increase in gene transcription relative to adult values. Within 48 h of exposure of 26-day explants to dexamethasone at 10(-8) M there was a rapid increase in SP-B mRNA levels to 7-fold adult levels. A similar overall although somewhat slower and attenuated pattern was observed with 30-day explants. Dexamethasone at 10(-8) M had no effect on SP-B gene transcription with explants of either gestational age. We conclude that the major effect of dexamethasone treatment in vitro on SP-B mRNA levels appears to be post-transcriptional and there are small but distinct differences in the effects of glucocorticoids on SP B mRNA levels with explant cultures from early and late stages of fetal lung maturation. PMID- 8343539 TI - Purification and characterization of Pseudomonas fluorescens SIK W1 lipase expressed in Escherichia coli. AB - Pseudomonas fluorescens SIK W1 lipase was expressed as a form of inclusion bodies in Escherichia coli, which was equivalent to 46% of total cell protein. The inclusion bodies isolated from other cell components were solubilized in the buffer containing 8 M urea and then refolded by diluting urea. The lipase with active conformation was purified by hydrophobic interaction chromatography, gel filtration, anion-exchange chromatography and hydroxyapatite chromatography from the refolded sample. By these purification steps, a single band for active lipase was detected on non-reducing SDS-PAGE and 10-fold purification was attained on the basis of specific activity. Specific activity of the purified lipase toward olive oil emulsion was found to be 7395 units per mg protein. The optimum pH and temperature of the lipase were pH 8.5 and 45-55 degrees C, respectively. The lipase showed higher lipolytic activity toward tricaproin (C6) and tricaprylin (C8) among the triacylglycerols examined and preferentially hydrolyzed ester bond of 1- and 3-position of triolein. Lipase activity was greatly increased by approx. 6-fold and stability for pH was shifted to alkaline pH by Ca2+ ion. The lipase was inhibited by Hg2+, Ag2+, p-chloromercuribenzoate, diethylpyrocarbonate and sodium dodecyl sulfate. PMID- 8343540 TI - A convenient evaluation of the stereoselectivity of lipase-catalyzed hydrolysis of tri-O-acylglycerols on a chiral-phase liquid chromatography. AB - A general method was developed using chiral-phase chromatography in order to evaluate the stereoselectivities of lipases-catalyzed hydrolysis of tri-O acylglycerols independent of acyl groups. 1,2-Di-O-acyl-sn-glycerols or its enantiomer 2,3-di-O-acyl-sn-glycerols in the enzymatic reaction mixtures were derivatized to the key compound, 1,2-di-O-benzoyl-3-O-tert-butyldimethylsilyl-sn glycerol 2 (+) or its enantiomer 2' (-), respectively. The enantiomers were separated on a chiral-phase HPLC, and the method was highly sensitive to determine the stereoselectivities of lipases. PMID- 8343541 TI - 1H-NMR spectroscopy can accurately quantitate the lipolysis and oxidation of cardiac triacylglycerols. AB - Triacylglycerol metabolism in isolated, perfused hearts from rats fed a diet containing 20% rapeseed oil (RSO) was studied using 1H-NMR spectroscopy. RSO induced elevation in cardiac triacylglycerols is associated with an increase in the peak area of fatty acid 1H-NMR resonances. The ratio of methyl, gamma methylene or methylene protons adjacent to a carbon-carbon double bond to the number of methylene protons in these hearts measured by 1H-NMR spectroscopy gives values similar to those derived from previously reported chemical analyses. In addition, the triacylglycerol content of these hearts determined by chemical analysis directly correlates with their content of 1H-NMR visible fatty acid resonances. This quantitative relationship allows the real-time measurement of the rates of cardiac triacylglycerol lipolysis using 1H-NMR spectroscopy. Rates of triacylglycerol lipolysis measured using 1H-NMR spectroscopy are similar to those previously measured by chemical methods. Triacylglycerol lipolysis measured using 1H-NMR spectroscopy occurs at a significantly faster rate in hearts perfused in the presence or absence of glucose when compared to hearts perfused with glucose and acetate or medium-chain fatty acids. Finally, the rate of triacylglycerol lipolysis in glucose perfused hearts is linearly related to work output. These results demonstrate that 1H-NMR spectroscopy can accurately quantitate triacylglycerol content and metabolism in the rapeseed oil-fed rat model. 1H-NMR spectroscopic or imaging techniques may be useful in the real-time evaluation of cardiac triacylglycerol content and metabolism. PMID- 8343542 TI - Purification of human gastric lipase by immunoaffinity and quantification of this enzyme in the duodenal contents using a new ELISA procedure. AB - Human gastric lipase (HGL) is the first lipolytic enzyme involved in the digestion of dietary lipids along the gastrointestinal tract. We describe an improved procedure for isolating the enzyme using immunoaffinity chromatography in combination with ion-exchange chromatography. The purified enzyme, showing a single band on SDS-PAGE, expressed a specific activity of 1000 U/mg using tributyrin as the substrate. We also describe a specific enzyme-linked immunosorbent assay (ELISA) procedure for measuring duodenal HGL levels. The ELISA was performed using an anti-HGL polyclonal antibody (pAb) as the captor antibody and a biotinylated monoclonal antibody (mAb) as the detector antibody. With the double sandwich ELISA technique, HGL in the range of 1-60 ng/ml was measured in less than 5 h. Identical HGL concentrations were obtained using the above ELISA procedure when compared to those based on the enzymatic activity using the potentiometric method (correlation coefficient: r = 0.95). No significant interference from other duodenal components was observed, as proved by the quantitative HGL determinations performed on intestinal samples. PMID- 8343543 TI - Increased hepatic monoacylglycerol acyltransferase activity in streptozotocin induced diabetes: characterization and comparison with activities from adult and neonatal rat liver. AB - Hepatic monoacylglycerol acyltransferase (EC 2.3.1.22) (MGAT) is a developmentally-expressed activity associated with physiological periods characterized by high rates of lipolysis and dependence on fatty acids for energy production. During these periods, MGAT may help to retain essential fatty acids selectively. In streptozotocin-diabetes, mean MGAT-specific activity increased 11.8-fold. We characterized microsomal MGAT activity from diabetic and control adult rats, and compared these adult activities with the high neonatal activity. Compared with the activity in neonatal liver, adult MGAT activity was more thermolabile, had a markedly different pH profile, and responded differently to incubation with bovine serum albumin, phospholipids, and MnCl2. Adult diabetic MGAT activity was also stimulated 2-fold by albumin and was markedly thermolabile, but was not inhibited by phospholipid. Diabetic MGAT activity had some properties that combined characteristics observed in adult and neonatal microsomes: a pH dependence that was optimal at pH 7.0 but that plateaued between pH 7.0 and 9.5, and neither stimulation nor inhibition after incubation with MnCl2. Diabetic MGAT acylated monoalkylglycerols more readily than did either the neonatal or the adult MGAT activities. The enhanced expression of hepatic MGAT activity in diabetes is consistent with its postulated role in retaining essential fatty acids during lipolysis. PMID- 8343544 TI - Comparison of the lipid and apolipoprotein composition of skeletal muscle and peripheral lymph in control dogs and in dogs fed a high fat, high cholesterol, hypothyroid-inducing diet. AB - Most studies of peripheral interstitial fluid lipoprotein composition have been made on interstitial fluid-derived from skin and connective tissue. We developed techniques which allowed simultaneous comparison of lymph (a model of interstitial fluid) from skeletal muscle and skin in control (C) and cholesterol fed (CF) dogs. Lipoprotein fractions were separated by ultracentrifugation. Skeletal muscle interstitial fluid HDL concentrations were approximately twice those of skin. However, the concentration of VLDL-LDL particles was similar in both interstitial spaces. HDL particles from both microvascular beds showed evidence of extensive remodelling when compared to plasma HDL from the same animal. Relative to apo A-I, skeletal muscle HDL was enriched in free cholesterol and apo E (C and CF dogs) and apo A-IV (CF dogs). Skin-derived HDL was consistently enriched in free cholesterol, apo E and A-IV in both C and CF dogs. These studies indicate that similar remodeling of plasma HDL occurs in widely different tissues which together constitute approximately 70% of the total interstitial space. The relatively high concentration of plasma-derived and remodeled HDL within the interstitial space of skeletal muscle is consistent with that tissue's importance in reverse cholesterol transport. PMID- 8343545 TI - Alterations by clofibric acid of glycerolipid metabolism in rat-kidney. AB - Alterations induced by p-chlorophenoxyisobutyric acid (clofibric acid) in glycerolipid metabolism in rat-kidney were studied. (1) The treatment of rats with clofibric acid markedly decreased renal level of triacylglycerol, which seemed to be due to a reduced formation of triacylglycerol, since the in vivo incorporation of [14C]oleic acid (18:1), [14C]linoleic acid (18:2) and [3H]glycerol into triacylglycerol was decreased in clofibric acid-fed rats. (2) The administration of clofibric acid to rats increased proportions of 18:1 and 18:2 and decreased a proportion of arachidonic acid (20:4) in phosphatidylcholine; the contents of two major molecular species of renal diacylglycerophosphocholine (diacyl-GPC), palmitoyl-arachidonoyl (16:0-20:4) and stearoylarachidonoyl (18:0-20:4), were both decreased markedly. The treatment did not alter renal content of phosphatidylcholine. (3) By contrast, clofibric acid changed, to a lesser extent, the composition of molecular species of diacylphosphatidylethanolamine. (4) The decrease in the level of diacyl-GPC that contains 20:4 seemed to be due to the clofibric acid-caused reduction in the concentration of free 20:4 in kidney. The reduction in renal concentration of free 20:4 seemed to be caused by a decrease in serum concentration of lipids that contain 20:4, but not by a decrease in the activities of desaturation and chain elongation that participate in biosynthesis of 20:4. (5) The reduction by clofibric acid in the renal content of diacyl-GPC containing 20:4 resulted in the decrease in the formation of prostaglandin E2 in kidney. PMID- 8343547 TI - Whose interest should have priority? Phase II: society's challenge for the next decade. PMID- 8343546 TI - Questions about child abuse? Consultation line created for physicians. PMID- 8343548 TI - Changes in medical care. PMID- 8343549 TI - Candidates for governor discuss health care issues. PMID- 8343550 TI - Abdominal actinomycosis, a common presentation of an increasingly uncommon infection. PMID- 8343551 TI - Urinary incontinence. PMID- 8343552 TI - Nursing diagnosis: a professional challenge for ET nursing. AB - ET nursing has an exciting and challenging opportunity to contribute to the advancement of nursing knowledge by the development of new nursing diagnoses and the revision of diagnoses already approved by the North American Nursing Diagnosis Association. This article discusses the significance of nursing diagnosis for nursing in general and ET nursing practice in particular. It also promotes exploration of the contribution ET nursing can offer through the common language of nursing diagnosis. PMID- 8343553 TI - Survey of the degree to which ET nurses are performing current procedural terminology-coded services. AB - ET nurses practice in many different settings including hospitals, home health, independent practice, and contract services. Reimbursement for their services is widely varied. To contribute meaningfully to health care reform, the services being provided by ET nurses must be identified. Familiarity with how these services overlap with those provided by other health care providers is essential. Current Procedural Terminology (CPT) codes, the language of payment within the health care system, are prepared and published annually by the American Medical Association for purposes of physician payment. Physicians are being paid for services that are also performed by ET nurses. This study identifies the CPT coded services used in the practice of the ET nurse and also codes that overlap those for which physicians are paid. Identification of ET nurse-provided CPT coded services delineates the ET nursing scope of practice and may serve as a foundation to address other practice issues, including reimbursement. PMID- 8343554 TI - Collaborative nurse management of multifactorial moist desquamation in a patient undergoing radiotherapy. AB - Consultation and collaboration between health care professionals can facilitate and improve patient care. In this case, Radiation Oncology and ET nurses collaborated in the care of a patient undergoing radiotherapy for esophageal carcinoma and concomitant corticosteroid therapy for cicatricial pemphigoid. The patient had moist skin desquamation during radiotherapy and was successfully treated by moist wound healing techniques with a hydrogel (Vigilon, C.R. Bard, Inc., Murray Hill, N.J.). The clinical success of nursing collaboration in this case affected assessment and treatment of moist desquamation in the Radiation Oncology department at one institution. PMID- 8343555 TI - ET nurses: on the front line of health care reform. AB - The most important challenge at the forefront of the national agenda is the need for health care reform. Major concerns of the current system are cost and access to care. This article discusses numerous congressional proposals and strategies for addressing these concerns. ET nurses are in a unique position to influence health care delivery. The Wound Ostomy and Continence Nurses Society has implemented strategies that position ET nurses as part of the solution to the health care crisis. ET nurses must also market themselves in their individual settings as key players in health care reform. PMID- 8343557 TI - Management of perineal and genital burns. AB - Burn injuries to the perineum and genitals present the bedside care provider with a unique set of management problems. Traditionally, thermal injuries to these areas have been allowed to close by secondary intention, with epithelialization occurring from remnants protected within skin folds. Partial-thickness wounds of the perineum and genitals must be kept clean and free of bacterial infection to prevent necrosis and development of full-thickness injury. Although full thickness thermal injuries to the penis and vulva are rare, they require special attention during the immediate postgrafting period to ensure complete engraftment. Control of scarring in this area requires tailor-made pressure garments, with customized inserts to provide controlled pressure to the skin folds. PMID- 8343556 TI - Twenty four-hour monitoring of incontinence and bladder function in a community hospital. AB - We wished to determine whether 24-hour monitoring of urinary incontinence without video urodynamics would provide adequate information for treatment. Twelve subjects with urinary incontinence (seven women and five men) were investigated, average age 75 years (range 44 to 89 years). Setting was a community hospital (80 beds), a nursing home, and a lodge, 60 miles from the nearest assessment center. Twenty four-hour monitoring consisted of 2 hourly preweighed pad changes, postchange weighing, Uroflow set-up in subject's bathroom, fluid intake record, and 1 postvoid residual ultrasonogram. All subjects had history and physical and evaluation of medications. Findings included probable urge incontinence, stress incontinence, chronic retention with overflow, and normal bladder function. Recommendations included oxybutynin chloride, timed toileting, timed fluid restriction, diuretic manipulation, intermittent catheterization, pessary, and surgery. At 6 weeks, 25% (4/12) were better (three with urge incontinence and one after operation for stress incontinence). Video urodynamics were conducted only for the patient with stress incontinence after operation. We suggest that 24-hour monitoring is noninvasive, is less disruptive and less expensive than video urodynamics, and provides adequate information for initial treatment in many patients with urinary incontinence. PMID- 8343558 TI - Options in practice: another option explored. PMID- 8343559 TI - In vitro tumour cell growth inhibition: a comparative study between allosensitized cytotoxic T lymphocytes and lymphokine activated killer cells. AB - There is general agreement that several distinct subpopulation of lymphocytes, including major histocompatibility complex (MHC)-restricted T lymphocytes and non restricted natural killer, or lymphokine-activated killer (LAK), cells are active in lysing neoplastic cells. In this study experiments were designed to compare the inhibitory effects of LAK cells and allosensitized cytotoxic T lymphocytes (CTL) on in vitro growth of an Epstein-Barr virus-transformed B-cell line (BSM) and of a HTLV-I producer T-cell line (MT-2). It was found that allosensitized CTL are more efficient at inducing BSM, or MT-2, cell growth inhibition than LAK cells. These results are consistent with the hypothesis that MHC-restricted T effector cells could mediate higher tumour suppressive effects than non-MHC restricted LAK cells. PMID- 8343560 TI - Characterization and enumeration of spontaneously proliferating human leucocytes by multiparameter flow cytometry. AB - Spontaneously proliferating human leucocytes have been characterized and enumerated using multiparameter flow cytometry. The frequency of spontaneously proliferating cells amongst human peripheral blood mononuclear cells, was determined on the basis of BrdUrd incorporation and total DNA content in samples of cells incubated in medium without added mitogen for several days. The frequency of proliferating cells decreased from an initial level of approximately 6 x 10(-4) to 3 x 10(-4) after 30 h of incubation, and then rose to approximately 2 x 10(-2) after 100 h of incubation. In one reference person, the frequency showed only minor variation in this pattern over a 1.5 year interval. Simultaneous measurement of proliferation and determination of immunological subclass, as indicated with Hoechst 33342 staining and surface markers, showed an over-representation of CD19-positive cells, compared with CD2-positive cells and subsets of CD2-positive cells (CD4-positives and CD8-positives). This method can be used as an indicator of exposure to agents when results from animal tests are to be compared with results from human populations. The advantages are that no cell culturing is needed to perform the test, it provides the possibility of further characterizing proliferating cells, and the rapid flow-cytometric enumeration. PMID- 8343561 TI - A simplified HPLC method for simultaneously quantifying ribonucleotides and deoxyribonucleotides in cell extracts or frozen tissues. AB - Agents and conditions that induce alterations in deoxyribonucleotide pools can have important regulatory effects on the rate of DNA synthesis as well as cell cycle progression. A simplified procedure for the separation of both ribonucleoside triphosphates (NTP) and deoxyribonucleoside triphosphates (dNTP) is presented which utilizes reversed phase high-performance liquid chromatography coupled with diode array detection. The simultaneous resolution of NTP and dNTP peaks within the same cell extract effectively eliminates the need for post extraction steps such as periodate oxidation and/or boronate affinity chromatography previously used to degrade or isolate co-eluting NTP from dNTP. The resolution of two nucleotides, dGTP and ADP, was found empirically to vary with the efficiency of the C18 column. High efficiency columns (> 90,000 plates/m) provided good separation; however, less efficient columns resulted in co-elution of dGTP and ADP. These co-eluting nucleotides can be accurately quantified, if necessary, using diode array technology and a mathematical expression which incorporates molar peak coefficients and peak areas obtained by monitoring at dual wave-lengths. Tissue samples or single cell suspensions were extracted with trichloroacetic acid and the neutralized extract was injected directly into the column without prior lyophilization. The per cent recovery of standards was > or = 99% and replicate extractions within or between samples were highly reproducible (SD < 5%). The single step method described minimizes potential losses associated with post-extraction manipulation and provides the capability to examine alterations in nucleotide precursor-product metabolism under various physiological and pharmacological conditions. PMID- 8343562 TI - Flow cytometric BrdUrd-pulse-chase study of heat-induced cell-cycle progression delays. AB - The flow cytometric, bromodeoxyuridine (BrdUrd)-pulse-chase method was extended by analysing five kinetic parameters to study perturbed cell progression through the cell cycle. The method was used to analyse the cell-cycle perturbations induced by heat shock. Exponentially growing, asynchronous Chinese hamster ovary (CHO) cells were pulse labelled with BrdUrd and simultaneously heated at 43 degrees C for 5, 10 or 15 min. The cells were then incubated in a BrdUrd-free medium and, at various times thereafter, were prepared for flow cytometry. Five compartments (BrdUrd-labelled divided and undivided, and unlabelled G1, G1S, and G2) were defined in the resulting dual-parameter histograms. The fraction of cells and the mean DNA content, when appropriate, were calculated for each compartment. The rates of cell-cycle progression were assessed as time-dependent changes in the fraction of cells in a given compartment and/or the relative DNA content of cells within a given compartment. Linear regression analysis of the data revealed two distinct modes of alteration in cell progression: 1 a delay in cell transit (either out of or into a given compartment), and 2 a decrease in the rate of cell transit. Hyperthermia produced a delay in the exit of cells from the G1 compartment of approximately 16 min per minute of heat at 43 degrees C with no threshold. In contrast, the delay in the exit of cells from all other compartments showed a threshold of from 3 to 5 min at 43 degrees C. Above this threshold the delay in exit of cells from the BrdUrd-labelled, undivided compartment was approximately 25 min per minute of heat at 43 degrees C. The more complex dose-response function of this latter compartment may reflect the fact that it includes two cell-cycle phases, S and G2 + M. The decrease in the rate of transit out of G2 for cells heated in G2 was significantly larger than that for any other compartment, consistent with previous studies, which showed a G2 accumulation following hyperthermia. These results indicate that heat exposure induces very complex alterations in cell-cycle progression and that this flow cytometric method offers a straightforward approach for observing such alterations. PMID- 8343563 TI - Evidence for altered cell-cycle traverse of the non-modal cells of the heteroploid MCa-11 line. AB - Classic stem cell theory states that the growth of heteroploid cell populations is due to the proliferation of 'main stemline' cells with modal DNA content and chromosome number. Cells with non-modal DNA content and chromosome number are thought to be blocked and/or destroyed at mitosis. To test this, we studied two chromosomally stable cell populations (mouse bone marrow and WCHE-5 cells) and one heteroploid, chromosomally diverse cell line (MCa-11). The heteroploid MCa-11 cells showed significant [3H]dT labelling for cells with DNA contents below the modal G0/G1 peak and above the modal G2 peaks (P < 0.001). This was consistent with the presence of cells with the non-modal DNA content that were engaged in replicative DNA synthesis. A percentage labelled mitosis analysis showed that MCa 11 cells with non-modal DNA content and chromosome number were able to complete mitosis, although with prolonged pre-karyokinetic time. These results suggest that many non-modal cells present in heteroploid cell populations are capable of continued proliferation. PMID- 8343564 TI - The Safe Medical Devices Act. PMID- 8343565 TI - Shadows and light. PMID- 8343566 TI - Evaluating damages in malpractice cases. PMID- 8343567 TI - Making direct mail work. PMID- 8343568 TI - Medical-legal Q & A. Utilization review. PMID- 8343569 TI - The interaction of DAPI with phospholipid vesicles and micelles. AB - The interactions of the dye 4',6-diamidino-2-phenylindole (DAPI) with phospholipids ordered in single bilayer vesicles of dioleylphosphatidylserine (DOPS) or dimyristoylphosphatidylcholine (DMPC) or micelles of monomyristoylphosphatidylcholine (MPC) have been investigated. Somewhat unexpectedly, the binding of this dye to such ordered structures is not affected by the ionic strength of the external medium, which suggests an embedding of DAPI into the hydrocarbon phase. The fluorescence enhancement of DAPI bound can be accomodated within a model previously proposed for the behaviour of DAPI bound to proteins (Mazzini et al., Biophys. Chem. 42 (1992) 101). From both static and dynamic anisotropy measurements, bound DAPI results severely restricted in its rotational freedom but insensitive to the temperature dependent phase transition of the saturated DMPC vesicles. The considerable tightness and specificity of the interactions between DAPI and ordered phospholipids are also deduced from preliminary fluorescence quenching studies (reduced accessibility of iodide ions towards DAPI bound and quenching effects by the chaotrop Nonidet P-40). PMID- 8343570 TI - Tryptophan mutants of human C5a anaphylatoxin: a fluorescence anisotropy decay and energy transfer study. AB - Three mutants of the anaphylatoxin C5a were prepared with positions 2, 64 and 70, respectively, substituted by tryptophan. The last mutant was additionally labelled at Cys27 for fluorescence energy transfer (FET) measurements. The structural integrity and biological activity of the molecules were not affected. Fluorescence anisotropy decay (FAD) measurements showed that the rotational correlation time for tryptophan decreases in the order: [Trp2]rhC5a > [Trp64]rhC5a > [Trp70]rhC5a, indicating an increasing mobility of the side chain. Measurements of the fluorescence energy transfer from Trp70 to the 1,5-AEDANS group at Cys27 yielded a distance distribution of 2.4 +/- 0.8 nm. This value is compatible with the C-terminal chain being arranged as a slightly stretched helix pointing away from the body of the molecule. PMID- 8343571 TI - Effect of linear reinsertion of receptor on the distribution of receptors around coated pits. AB - We consider a linear receptor reinsertion step in our kinetic model of the primary steps occurring in receptor-mediated endocytosis. In contrast with our previous zeroth order receptor reinsertion assumption, here we consider a first order process, and we study the effect of receptor diffusion on the trapping rate constant (k+) and the radial distribution of receptors around coated pits (grp). Using experimental data for low density lipoproteins (LDL) receptors on fibroblast cells, we find that the trapping of receptors by coated pits is diffusion-controlled for any value of the escaping rate constant (k-). This result is significantly different from our previous findings. In fact, for a zeroth order process, we find that either diffusion has no effect on k+ or, at the most, receptor trapping is 84% diffusion-controlled. Moreover, we find values for the receptor reinsertion rate constant (kappa), which range between 15% of the pit's invagination rate constant, lambda, and three halves lambda. In addition, the ratio kappa/lambda is equal to the ratio of the concentration of receptors in pits with respect to the internalized receptors. Comparison between the experimental radial distribution of receptors around pits and the theoretical should provide an indication of the diffusion effect on k+. PMID- 8343572 TI - End-to-end diffusion coefficients and distance distributions from fluorescence energy transfer measurements: enhanced resolution by using multiple acceptors with different Forster distances. AB - We measured distance distributions and end-to-end diffusion coefficients of donor acceptor pairs linked by a flexible methylene chain using frequency-domain fluorescence energy transfer measurements. The donor was an indole group, and two acceptors with different Forster distances were used. The uncertainties in the recovered parameters describing the end-to-end distance distribution and diffusion coefficient were rather large when each donor-acceptor pair was analyzed separately. It was not possible to resolve distance distributions in the presence of intra-molecular diffusion when the Forster distance was comparable to the mean and half-width of the distribution. Global analysis using two acceptors dramatically improved the resolution. Surprisingly, the Forster distances need not be very different, and a 20% difference between the two R0 values resulted in substantial improvements in resolution. Both the simulations and the experiments suggest the benefit of using global analysis with different Forster distances to obtain reliable distance distribution parameters in the presence of diffusion. PMID- 8343573 TI - Structure and dynamics of peptide-polynucleotide complexes. AB - The mode and the dynamics of LysTrpLys-binding to double helical DNA and to single stranded poly(A) has been analyzed by measurements of the chemical relaxation detected by fluorescence and of the rotational diffusion using the electric dichroism. The chemical relaxation, induced by electric field pulses, requires two exponentials for a satisfactory representation, indicating a two step reaction mechanism. The data are consistent with a bimolecular reaction step followed by a relatively slow intramolecular transition, which is expected to reflect "insertion" of the Trp-indole residues between the nucleic acid bases. The experimental data are analyzed quantitatively by global fitting with exact correction of the convolution due to the experimental device. In this procedure a complete set of relaxation curves is fitted directly to the reaction model and, thus artifacts resulting from erroneous assignments of coupled modes are avoided. According to this analysis the bimolecular reaction step is controlled by diffusion. The intramolecular transition in adenylate chains is found to be dependent on the chain length and on the ionic strength I: at I = 2.5 mM the "insertion" rate constant is 3 x 10(4) s-1 for the polymer and 2 x 10(5) s-1 for A(pA)19; the rate constant for poly(A) increases with increasing salt concentration. The corresponding "insertion" rate constant for DNA double helices with 30 kbp is 2.5 x 10(4) s-1. For DNA double helices we find again an increase of the "insertion" rate with increasing salt concentration and with decreasing chain length. The mode of LysTrpLys-binding to double helical DNA is compared with that of LysTyrLys, LysLeuLys and LysGlyLys by measurements of the rotational diffusion of complexes with restriction fragments of different chain lengths. The persistence lengths derived from these measurements do not reveal any special effects resulting from insertion of aromatic residues. Apparently "insertion" of indole rings into double helical DNA does not increase the length of the double helix, which may be attributed to a special form of insertion, e.g. partial insertion. According to these results the interaction of the indole residues of LysTrpLys with DNA double helices is not equivalent to e.g. intercalation of aromatic residues like ethidium-neither with respect to structure nor to dynamics. PMID- 8343574 TI - Lattice vibrations in crystalline L-alanine. AB - Zwitterionic L-alanine forms crystals containing strong hydrogen-bonding and methylmethyl interactions. Well-defined low-frequency lattice vibrations exist in the crystals involving correlated intermolecular motions on the picosecond timescale. A characterization of these vibrations is expected to provide useful information on the nature of nonbonded interactions in peptides and proteins. We examine some of the vibrations using coherent inelastic neutron scattering and computer simulation techniques. The neutron scattering measurements are used to determine phonon dispersion relations for the acoustic and some low-frequency optic modes in the crystal. There is evidence for interaction between the two lowest frequency optical phonons and the longitudinal acoustic mode. The velocity of sound is anisotropic and can be correlated with the hydrogen-bonding arrangement in the crystal. Corresponding phonon dispersion relations are derived from normal mode analyses of the crystal using the program CHARMM. Although some calculated vibrational frequencies are somewhat too high, the form of the calculated dispersion relations are in good agreement with experiment. PMID- 8343575 TI - Molecular dynamics of sickle and normal hemoglobins. AB - Molecular dynamics (MD) simulations have been carried out for 62.5 ps on crystal structures of deoxy sickle cell hemoglobin (HbS) and normal deoxy hemoglobin (HbA) using the CHARMM MD algorithm, with a time step of 0.001 ps. In the trajectory analysis of the 12.5-62.5 (50 ps) simulation, oscillations of the radius of gyration and solvent-accessible surface area were calculated. HbS exhibited a general contraction during the simulation, while HbA exhibited a nearly constant size. The average deviations of simulated structures from the starting structures were found to be 1.8 A for HbA and 2.3 A for HbS. The average rms amplitudes of atomic motions (atomic flexibility) were about 0.7 A HbA and about 1.0 A for HbS. The amplitudes of backbone motion correlate well with temperature factors derived from x-ray crystallography. A comparison of flexibility between the alpha- and beta-chains in both HbA and HbS indicates that the beta-chains generally exhibited greater flexibility than the alpha-chains, and that the HbS beta-chains exhibit greater flexibility in the N-terminal and D- and F-helix regions than do those of HbA. The average amplitude of backbone torsional oscillations was about 9 degrees, a value comparable with that of other simulations, with enhanced torsional oscillation occurring primarily at the ends of helices or in loop regions between helices. Comparison of atomic flexibility and torsional oscillation results suggests that the increased beta-chain flexibility results from relatively concerted motions of secondary structure elements. The increased flexibility may play an important role in HbS polymerization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343576 TI - Self-assembly of bioelastomeric structures from solutions: mean-field critical behavior and Flory-Huggins free energy of interactions. AB - Elastic and quasi-elastic light scattering studies were performed on aqueous solutions of poly(Val-Pro-Gly-Gly), a representative synthetic bioelastomer that differs from the previously studied poly(Val-Pro-Gly-Val-Gly) by the deletion of the hydrophobic Val in position four. When the spinodal line was approached from the region of thermodynamic stability, the intensity of light scattered by fluctuations, and the related lifetime and correlation length, were observed to diverge with mean-field critical exponents for both systems. Fitting of the experimental data allowed determining the spinodal and binodal (coexistence) lines that characterize the phase diagrams of the two systems, and it also allowed a quantitative sorting out of the enthalpic and entropic contributions to the Flory-Huggins interaction parameters. The contribution of valine is derived by comparison of the two cases. This can be viewed as sorting out the effect of a modulation of the solute. The same approach may allow sorting out the entropic and enthalpic effect of modulations of the solvent by cosolutes (or by cosolvents). This could be of particular interest in the case of small osmolytes, affording important adaptive roles in nature, at the cost of very limited changes in genetic information. Finally, the suggestion is further supported that statistical fluctuations of anomalous amplitude, such as those occurring in proximity of the spinodal line, have a role in promoting the process of self assembly of extended supramolecular structures. On the practical side, the present approach appears useful in the design of novel synthetic model systems for bioelastomers. PMID- 8343577 TI - Further characterization of the kinetic folding intermediate of alpha alpha tropomyosin and of its 142-281 subsequence. AB - The backbone CD spectrum from 250 to 212 nm for the kinetic folding intermediate of alpha alpha-tropomyosin (alpha alpha-Tm) and nonpolymerizable alpha alpha-Tm was obtained. The spectrum shows that the intermediate is indeed alpha-helical with about 70% of the equilibrium alpha-helix content. Subsequence 142Tm281 of the alpha-tropomyosin chain has five tyrosine residues (at positions 162, 214, 221, 261, 267). Stopped flow CD at the negative peak in the tyrosine spectral region (280 nm) shows that any tyrosine residues that contribute to the spectrum in the region have already reached their final state in the fast phase of folding (< 0.04 s). PMID- 8343578 TI - Unfolding of an alpha-helix in peptide crystals by solvation: conformational fragility in a heptapeptide. AB - The structure of the peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe has been determined in crystals obtained from a dimethylsulfoxide-isopropanol mixture. Crystal parameters are as follows: C38H69N7O10.H2O.2C3H7OH, space group P2(1), a = 10.350 (2) A b = 26.084 (4) A, c = 10.395 (2) A, beta = 96.87 (12), Z = 2, R = 8.7% for 2686 reflections observed > 3.0 sigma (F). A single 5-->1 hydrogen bond is observed at the N-terminus, while two 4-->1 hydrogen bonds characteristic of a 3(10)-helix are seen in the central segment. The C-terminus residues, Ala(6) and Leu(7) are extended, while Val(5) is considerably distorted from a helical conformation. Two isopropanol molecules make hydrogen bonds to the C-terminal segment, while a water molecule interacts with the N-terminus. The structure is in contrast to that obtained for the same peptide in crystals from methanol-water [I. L. Karle, J. L. Flippen-Anderson, K. Uma, and P. Balaram (1990) Proteins: Structure, Function and Genetics, Vol. 7, pp. 62-73] in which two independent molecules reveal an almost perfect alpha-helix and a helix penetrated by a water molecule. A comparison of the three structures provides a snapshot of the progressive effects of solvation leading to helix unwinding. The fragility of the heptapeptide helix in solution is demonstrated by nmr studies in CDCl3 and (CD3)2SO. A helical conformation is supported in the apolar solvent CDCl3, whereas almost complete unfolding is observed in the strongly solvating medium (CD3)2SO. PMID- 8343579 TI - Probing protein structure by solvent perturbation of NMR spectra. II. Determination of surface and buried residues in homologous proteins. AB - The experimental assignment of most residues in a protein to the surface or interior is in principle possible without prior solution of a complete three dimensional structure. The method described is based on nmr measurements that determine the amino acid composition of the surface of a protein [A. Petros, L. Mueller, and K.D. Kopple (1990) Biochemistry, Vol. 29, pp. 10041-10048; G. Esposito, A. M. Lesk, H. Molinari, A. Motta, N. Niccolai, and A. Pastore (1992) Journal of Molecular Biology, Vol. 224, pp. 659-670]. If these measurements are carried out on several homologous proteins of known sequence, it is possible to combine the results to determine, in most cases, which positions in the sequence contain exposed residues. PMID- 8343580 TI - A method for studying the structure of uniaxially aligned biopolymers using solid state 15N-nmr: application to Bombyx mori silk fibroin fibers. AB - Recent advances in the application of solid state nmr spectroscopy to uniformly aligned biopolymers have opened a window through which to view the detailed structure of biological macromolecules that are unable to be seen with standard techniques for structure determination such as x-ray diffraction. Atomic resolution structural details are obtained from solid state nmr data in the form of bond orientations, which yield the relative positions of specific atoms within the molecule. For static aligned systems such as fibers, in which rapid reorientation about the axis of alignment does not occur, it has generally been necessary to perform trial and error line-shape simulations to extract structural details from nmr spectra arising from a single type of nuclear spin interaction. In the present work, a new method is developed in which solid state 15N-nmr spectra obtained from uniaxially aligned molecules placed with the axis of alignment both parallel and perpendicular to the magnetic field are analyzed to yield the orientations of specific molecular bonds. Analytical expressions are derived that utilize spectral features read from 15N chemical shift anisotropy line shapes to calculate a discrete number of possible orientations for a specific site. The 15N-1H dipolar interaction is employed to further narrow the number of unique orientations possible for a given site. With this method, a neighborhood of possible orientations is quickly determined, and full line-shape simulations within this region of allowed space can be performed to refine the limits of orientation. This technique demonstrates the use of a single type of isotopic label to determine the orientation of a specific molecular group such as a peptide plane within a protein. Results from the application of this method to the Bombyx mori silk fibroin protein provide structural detail that is consistent with currently accepted structural models based on fiber diffraction studies. PMID- 8343581 TI - Special issue: 3rd Naples Workshop on Conformational Analysis of Peptides: Relationships and Interactions. Capri, May 24-27, 1992. PMID- 8343582 TI - Improved molecular dynamics simulations for the determination of peptide structures. AB - In this article a few methods or modifications proven to be useful in the conformational examination of peptides and related molecules by molecular dynamics are illustrated. The first is the explicit use of organic solvents in the simulations. For many cases such solvents are appropriate since the nmr measurements (or other experimental observations) were carried out in the same solvent. Here, the use of dimethylsulfoxide and chloroform in molecular dynamics is described, with some advantages of the use of these solvents high-lighted. A constant allowing for the scaling of the nonbonded interactions of the force field, an idea previously employed in distance geometry and simulated annealing, has been implemented. The usefulness of this method is that when the nonbonded term is turned to zero, atoms can pass through each other, while the connectivity of the molecule is maintained. It will be shown that such simulations, if a sufficient driving force is present (i.e., nuclear Overhauser effects restraints), can produce the correct stereoconfiguration (i.e., chiral center) as well as configurational isomer (i.e., cis/trans isomers). Lastly, a penalty term for coupling constants directly related to the Karplus curve has been implemented into the potential energy force field. The advantages of this method over the commonly used dihedral angle restraining are discussed. In particular, it is shown that with more than one coupling constant about a dihedral angle a great reduction of the allowed conformational space is obtained. PMID- 8343584 TI - Noncoded residues as building blocks in the design of specific secondary structures: symmetrically disubstituted glycines and beta-alanine. AB - Structural changes can be induced in a peptide by selective substitution of coded alpha-amino acid residues by noncoded alpha-amino acid residues and the consequent production of analogues with modified structure and conformational preferences. In this review article we summarize the solid state structural results and the conformational preferences of two classes of "building blocks": (a) the linear and cyclic symmetrically alpha, alpha-disubstituted glycines in which either two identical n-alkyl groups replace the hydrogen atoms of the glycine residue or a cyclic aliphatic side-chain system is formed by linking the two alpha-carbon side chains, respectively; and (b) the beta-alanine residue. Examples, whenever possible, of the use of these residues for the elucidation of the bioactive conformation in the appropriate biological systems will be given. PMID- 8343583 TI - CD of proline-rich polypeptides: application to the study of the repetitive domain of maize glutelin-2. AB - An overview of CD of proline-rich peptides is reported. First, structural characteristics, theoretical CD studies, and the biological relevance of polyproline II structure in such peptides are discussed. Second, a CD study of peptides belonging to the repetitive domain of maize glutelin-2, H-(Val-His-Leu Pro-Pro-Pro)n-OH (n = 3, 5, 8), is described. This series of peptides displayed the CD features of polyproline II structure in water (5 degrees C, pH 5). Moreover, it was shown that the addition of increasing amounts of the polyanionic molecule heparin forced a displacement of the conformational equilibrium of those peptides toward higher proportions of the polyproline II structure. In contrast, when the temperature is raised such a structure gradually disappears, leading to more disordered conformations. PMID- 8343585 TI - Structures of peptides from alpha-amino acids methylated at the alpha-carbon. AB - The structural preferences of peptides (and depsipeptides) from the achiral MeAib and Hib residues, and the chiral Iva, (alpha Me) Val, (alpha Me) Leu, and (alpha Me) Phe residues, as determined by conformational energy computations, x-ray diffraction analyses, and 1H-nmr and spectroscopic studies, are reviewed and compared with literature data on Aib-containing peptides. The results obtained indicate that helical structures are preferentially adopted by peptides rich in these alpha-amino acids methylated at the alpha-carbon. Intriguing experimental findings on the impact of the chirality of Iva, (alpha Me) Val, and (alpha Me) Phe residues on helix screw sense are illustrated. PMID- 8343586 TI - Bioactive peptides: conformational study of a cystinyl cycloheptapeptide in its free and calcium complexed forms. AB - The disulphide bridged heptapeptide Boc-Cys-Val-Pro-Pro-Phe-Phe-Cys-OMe has been synthesized by classical solution methods. An ion binding study showed the peptide's ability to complex calcium ions with definite stoichiometry. The solution conformation of the peptide in its free and calcium-complexed form has been investigated by CD and nmr. The model structure derived from nmr data has been energy minimized and the resulting structure investigated by molecular dynamics simulation in water. The structure of the equimolar peptide/Ca2+ complex in acetonitrile at room temperature shows the presence of two transannular hydrogen bonds, with the formation of two ring structures of the C10 (type VIa) and C14 type. One peptide unit (Pro-Pro) is cis, all others are trans. PMID- 8343587 TI - Crystal structures of two cyclic pseudopentapeptides containing psi[CH2S] and psi[CH2SO] backbone surrogates. AB - The solid state conformations of cyclo [Gly-Pro psi[CH2S] Gly-D-Phe-Pro] and cyclo [Gly-Pro psi[CH2-(S)-SO]Gly-D-Phe-Pro] have been characterized by X-ray diffraction analysis. Crystals of the sulfide trihydrate are orthorhombic, P2(1)2(1)2(1), with a = 10.156(3) A, b = 11.704(3) A, c = 21.913(4) A, and Z = 4. Crystals of the sulfoxide are monoclinic, P2(1) with a = 10.662(1) A, b = 8.552(3) A, c = 12.947(2) A, beta = 94.28(2), and Z = 2. Unlike their all-amide parent, which adopts an all-trans backbone conformation and a type II beta-turn encompassing Gly-Pro-Gly-D-Phe, both of these peptides contain a cis Gly1-Pro2 bond and form a novel turn structure, i.e., a type II' beta-turn consisting of Gly-D-Phe-Pro-Gly. The turn structure in each of these peptides is stabilized by an intramolecular H bond between the carbonyl oxygen of Gly1 and the amide proton of D-Phe4. In the cyclic sulfoxide, the sulfinyl group is not involved in H bonding despite its strong potential as a hydrogen-bond acceptor. The crystal structure made it possible to establish the absolute configuration of the sulfinyl group in this peptide. The two crystal structures also helped identify a type II' beta-turn in the DMSO-d6 solution conformers of these peptides. PMID- 8343588 TI - Solid state and solution structure of Boc-L-Ala-delta Phe-delta Phe-NHMe: a dehydropeptide showing propensity for 3(10)-helices of both screw senses. AB - The crystal and molecular structure of the peptide Boc-L-Ala-delta Phe-delta Phe NHMe, containing two consecutive dehydro-phenylalanine (delta Phe) residues, has been solved by x-ray diffraction. Two independent molecules, X and Y, are present in the crystallographic unit. Their conformation corresponds approximately to an incipient 3(10)-helix stabilized by two intramolecular hydrogen bonds. The (phi, psi) torsion angles, however, have negative and positive signs in the two molecules X and Y, respectively. Therefore, in spite of the presence of an amino acid residue of the L configuration, the two helical molecules have opposite screw senses, even though the right-handed helix is less distorted than the left handed one in correspondence of the L-Ala residue. The CD spectra in various solvents exhibit exciton bands originating from dipole-dipole interaction between the delta Phe side chains. Addition of DMSO to the chloroform solution produces, as a first step, a strong increasing of the CD bands, which are then progressively canceled by increasing DMSO concentration. The nmr data parallel the behavior observed in the CD spectra. In CDCl3 solution, the temperature coefficients of the NH resonances are consistent with the involvement of the last two amide protons of the sequence in intramolecular hydrogen bonds, but only negligibly small nuclear Overhauser effects (NOE) are observed. Addition of 5% DMSO-d6 allows the observation of diagnostic NOEs. CD and nmr data indicate that the solid state structure is retained in solution, and are consistent with the presence of right-handed and left-handed conformers, with a prevalence of the more stable right-handed one. PMID- 8343590 TI - The evaluation and interpretation of cervical cytology: application of the likelihood ratio concept. AB - The Papanicolaou smear (Pap test), used for the detection and prevention of neoplastic lesions of the cervix, is known to have both false negative and false positive results. Proper handling of the diagnostic uncertainty resulting from these errors demands quantification of flaws. Traditionally, sensitivity, specificity and predictive values are used for that aim. In this study another approach is advocated, namely the use of the likelihood ratio. For cervical cytology this ratio is the quotient of the probability of a Pap class within the diseased population to the probability of that same Pap class within the non diseased group. This approach enables the characterization of each Pap class separately, and is therefore much better for clinical interpretation of the result. It is also a superior approach for quality assessment. PMID- 8343589 TI - Conformational requirements for molecular recognition of acetylcholine receptor main immunogenic region (MIR) analogues by monoclonal anti-MIR antibody: a two dimensional nuclear magnetic resonance and molecular dynamics approach. AB - The conformational properties of two [D-A70, A76] and [Aib70, A76] analogues of the alpha 67-76 Torpedo acetylcholine receptor fragment, with low binding capacity for the anti main immunogenic region (MIR) antibodies, were studied in DMSO by two-dimensional nmr techniques and molecular dynamics simulations. The results were compared to the free and bound conformations of the [A76] analogue, which has twice more affinity for the anti-MIR monoclonal antibody 6 (mAb6), than the natural Torpedo sequence. It appeared that a single substitution of the A70, at a crucial position, by the D-A70 or Aib70, could modify completely the conformational behavior of the peptide and reduced its recognition by the anti MIR antibody. The WNPADY rigid structure at the N-terminal part was essential for antibody recognition. The adjacent more flexible C-terminal sequence (GGIK) gives additional stability to the monoclonal antibody-peptide complex probably due to an adequate orientation of the peptide side chains in the complex, by setting them in close contact with the antibody. PMID- 8343591 TI - Ciliary ultrastructure in nasal brushings. AB - Normal ciliary ultrastructure is thought to be necessary for effective function. There has been little or no attempt to quantify ultrastructural abnormalities in nasal disease and assess their significance. In this study we measured nasal ciliary function and examined ciliary ultrastructure in nasal brushings from 35 patients with perennial nasal symptoms refractory to treatment. Ultrastructural defects included microtubular abnormalities, compound cilia and ciliary 'blebs'. The incidence of abnormal cilia was 16.7%, compared with 9% in controls, but there was only a poor correlation between ultrastructural defects and ciliary beat frequency. One patient had primary ciliary dyskinesia (PCD) with a typical clinical history and immotile cilia. However, only secondary ultrastructural abnormalities were seen. We have been unable to show that ciliary ultrastructural defects form the basis of impaired function. In patients with suspected PCD, nasal brushings should be taken for functional and ultrastructural studies; ideally, a further sample should be obtained for examination of possible primary ultrastructural abnormalities. PMID- 8343592 TI - Evidence that the sensitivity is increased and the inadequacy rate decreased when pathologists take aspirates for cytodiagnosis. AB - The results of the diagnostic accuracy of breast fine needle aspiration specimens taken by the pathologist in a joint surgical clinic are compared with those taken by a surgeon. In the joint clinic the complete sensitivity rose by 15% and the number of missed malignancies fell by half. PMID- 8343593 TI - A case of pilomatrixoma misdiagnosed as squamous cell carcinoma. PMID- 8343594 TI - Prolapsed fallopian tube after abdominal hysterectomy: a report of the cytological findings. PMID- 8343595 TI - A poplar tree proteinase inhibitor-like gene promoter is responsive to wounding in transgenic tobacco. AB - Wounding of poplar trees leads to the accumulation of several mRNA species that encode proteins with putative defensive function. One class of wound-induced poplar RNA (win3) has amino acid sequence similarity to Kunitz-type trypsin inhibitors. Northern blots and cDNA sequencing show that several win3 mRNAs accumulate in the uninjured leaves of wounded trees. We report further characterization of the win3 family including sequence comparisons, gene family organization, and the identification of one win3 member that is transcriptionally activated in response to mechanical wounding. We also show that 1.5 kb of 5' flanking sequence of one win3 member (win3.12) is sufficient to confer wound regulated expression of a beta-D-glucuronidase (GUS) reporter gene in transgenic tobacco. Annual herbaceous plants such as tobacco can thus be used to study the expression of genes from a perennial woody angiosperm. PMID- 8343597 TI - Identification and genetic analysis of normal and mutant phytoene synthase genes of tomato by sequencing, complementation and co-suppression. AB - A tomato phytoene synthase gene, Psy1, has recently been isolated as the clone GTOM5 and shown by sequence identity to be the gene from which the major fruit ripening cDNA clone TOM5 was derived. Sequence analysis of transcripts from two allelic yellow-fruited tomato mutants, mapped to chromosome 3, has shown the lack of carotenoids in fruit of these mutants to be due to the production of aberrant TOM5 transcripts which are unlikely to encode a functional phytoene synthase enzyme. In one mutant (yellow flesh) the aberrant transcript contained a sequence that, by its strong hybridization to a wide size range of genomic fragments, appeared to be repeated many times within the genome. Southern and PCR analysis of the phytoene synthase genes in the mutant revealed restriction fragment length polymorphisms, suggesting that the production of altered mRNAs was associated with specific genomic rearrangements. Constitutive over-expression of a TOM5 cDNA clone in transgenic mutant plants restored synthesis of the carotenoid lycopene in ripening fruit and also led to unscheduled pigment production in other cell types. In some mutant plants transformed with the TOM5 cDNA construct, inhibition of carotenoid production in immature green fruit, leaves and flowers was observed, due to the phenomenon of co-suppression, indicating that different insertion events with the same gene construct can lead to overexpression or co suppression in transgenic plants. Green organs of these plants were susceptible to photobleaching, due to the lack of carotenoids. These results suggest the existence of separate Psy genes for carotenoid synthesis in green organs. PMID- 8343596 TI - Systemic induction of a potato pin2 promoter by wounding, methyl jasmonate, and abscisic acid in transgenic rice plants. AB - To address the question whether common signal(s) and transduction pathways are used to mediate a systemic wound response in monocot and dicot plants, a fusion of the potato proteinase inhibitor II gene (pin2) promoter and the bacterial beta glucuronidase gene (Gus)-coding region was introduced into rice. In transgenic rice plants, the expression of the pin2-Gus fusion gene displays a systemic wound response, although the expression level is relatively low. Incorporation of the first intron from the rice actin 1 gene (Act1) into the 5'-untranslated region of the pin2-Gus construct results in high-level, systemically wound-inducible expression of the modified construct in transgenic rice plants. Histochemical analysis shows that this high-level, wound-inducible expression is associated with the vascular tissue in both leaves and roots. Furthermore, the expression of the pin2-Act1 intron-Gus fusion gene in transgenic rice plants can be systemically induced by both methyl jasmonate (MJ) and the phytohormone abscisic acid (ABA). These results suggest that the signal(s) mediating the observed systemic wound response and certain steps of the transduction pathways are conserved between dicot and monocot plants. Transient expression assays show that the pin2-Act1 intron-Gus construct is also actively expressed in transformed cells and tissues of several other monocot plants. Thus, the wound-inducible pin2 promoter in combination with the rice Act1 intron 1 might be used as an efficient regulator for foreign gene expression in transgenic monocot plants. PMID- 8343598 TI - Chromosomal locations of the genes for histones and a histone gene-binding protein family HBP-1 in common wheat. AB - The chromosomal locations of the genes in common wheat that encode the five histones and five members of the HBP (histone gene-binding protein)-1 family were determined by hybridizing their cloned DNAs to genomic DNAs of nullitetrasomic and telosomic lines of common wheat, Triticum aestivum cv. Chinese Spring. The H1 and H2a genes are located on different sets of homoeologous chromosomes or chromosome arms, namely, 5A, 5B and 5D, and 2AS, 2BS and 2DS, respectively. Genes for the other histones, H2b, H3 and H4, are found in high copy number and are dispersed among a large number of chromosomes. The genes for all members of the HBP-1 family are present in small copy numbers. Those for HBP-1a(1) are located on six chromosome arms, 3BL, 5AL, 5DL, 6AL, 6BS and 7DL, whereas those for each HBP-1a(c14), 1a(17), 1b(c1), and 1b(c38) are on a single set of homoeologous chromosome arms; 4AS, 4BL, 4DL; 6AS, 6BS, 6DS; 3AL, 3BL, 3DL; and 3AS, 3BS, 3DS, respectively. The genes for histones H1 and H2a, and for all members of the HBP-1 family except HBP-1a(1) are assumed to have different phylogenetic origins. The genes for histone 2a and HBP-1a(17) are located in the RFLP maps of chromosomes 2B and 6A, respectively. Gene symbols are proposed for all genes whose chromosomal locations have been determined. PMID- 8343599 TI - A structural and evolutionary analysis of a dispersed repetitive sequence. AB - A family of dispersed repetitive sequences (Hch1) which is present in the genome of the wild barley Hordeum chilense was studied in detail. Hch1 sequences are found both as part of short tandem arrays and dispersed throughout the H. chilense chromosomes. Subcloning of sections of the sequence reveals that it is composed of unrelated classes of sequences which can also be found separately in other genomic locations. Analysis of these sequences in the genomes of wheat and two other wild barley species strongly suggests that specific amplifications and arrangements of the repeated sequences have taken place during speciation. Nucleotide sequence analysis fails to detect, in their entirety, the features shown by plant transposons. PMID- 8343600 TI - The psbB gene cluster of the Chlamydomonas reinhardtii chloroplast: sequence and transcriptional analyses of psbN and psbH. AB - We have sequenced and characterized the complete psbB gene cluster of Chlamydomonas reinhardtii chloroplast DNA. Although the petB and petD genes are located elsewhere, the sequential order of psbB, ORF31, psbN and psbH is identical to that of the psbB operon in higher plants. Also, intergenic non coding regions are much larger in the Chlamydomonas gene cluster. Northern blot analyses indicate the formation of dicistronic transcripts of psbB and ORF31 and monocistronic transcripts of psbN and psbH. It is unclear whether a psbB operon is transcribed to yield a large polycistronic precursor but northern blot analysis with total RNA from cells grown at 15 degrees C does not detect an increased complexity of the transcripts, as has been found in studies of the psbB operon of higher plants. From primer extension and nuclease protection assays, it is apparent that 5' and 3' processing of the primary psbH transcript results in the accumulation of a heterogenous population of mRNAs. Northern blot analyses reveal transcription of Chlamydomonas psbN and show that its mRNA is much larger than that identified in liverwort and pea. The sequence identities of the PSII-H and PSII-N polypeptides as compared to their vascular plant counterparts is 50 to 62%. While the amino acid sequences of PSII-H and PSII-N proteins are significantly conserved, the mass of PSII-H from Chlamydomonas is significantly larger. PMID- 8343601 TI - Differential expression of bean chitinase genes by virus infection, chemical treatment and UV irradiation. AB - Three chitinases have been shown previously to be induced upon various stresses of bean leaves. Time course studies of mRNA accumulation of two of them (P3- and P4-chitinases) have been studied upon virus infection, mercuric chloride treatment and UV irradiation. In alfalfa mosaic virus (AlMV)-infected plants both mRNAs, absent in uninfected bean leaves, become detectable 36 h after inoculation. A maximum level of mRNAs is reached 84 h after inoculation and, whereas the amount of P3-ch mRNA decreases soon after having reached the maximum, the amount of P4-ch mRNA remains at high levels for several days. In mercuric chloride-treated leaves P4-ch mRNA becomes detectable 1-1.5 h after onset of treatment and a maximum level is observed between 6 h and 24 h after treatment; P3-ch mRNA becomes detectable later than P4-ch mRNA in treated leaves and reaches a maximum as late as 18 h after treatment has been applied. UV light also induces the synthesis of both mRNAs but, here again, important differences are observed in the accumulation rate of the two transcripts. The relative amounts of each mRNA induced by the different stresses have been compared. The most effective inducer of P3-ch mRNA is AlMV. In contrast, mercuric chloride induces P4-ch mRNA more efficiently than AlMV or UV light. We have also determined the complete nucleotide sequence of the cDNA encoding P3-chitinase that has been isolated from a cDNA library by using the cucumber lysozyme-chitinase cDNA as a probe. The 1072 bp P3-ch cDNA encodes a mature protein of 268 amino acid residues and the 25 residue NH2-terminal signal peptide of the precursor. Because of its high structural homology to the cucumber and Arabidopsis acidic chitinases as well as to the N-terminal amino acid sequence of the bifunctional lysozyme-chitinase from P. quinquifolia, bean P3-chitinase can be considered to belong to the class III chitinases. Southern blot analysis of bean genomic DNA revealed that P3-chitinase is encoded by a single gene. PMID- 8343602 TI - A complex ensemble of cis-regulatory elements controls the expression of a Vicia faba non-storage seed protein gene. AB - We have identified cis-regulatory elements within the 5'-upstream region of a Vicia faba non-storage seed protein gene, called usp, by studying the expression of usp-promoter deletion fragments fused to reporter genes in transgenic tobacco seeds. 0.4 kb of usp upstream sequence contain at least six, but probably more, distinct cis-regulatory elements which are responsible for seemingly all quantitative, spatial and temporal aspects of expression. Expression-increasing and -decreasing elements are interspersed and include an AT-rich sequence, a G box element and a CATGCATG motif. The latter acts as a negative element in contrast to what has been found for the same motif in legumin- and vicilin-type seed storage protein gene promoters. Seed specificity of expression is mainly determined by the -68/+51 region which confers, however, only very low levels of expression. The data support the combinatorial model of promoter function. PMID- 8343604 TI - High evolutionary divergence of the 5.8S ribosomal DNA in Mimulus glaucescens (Scrophulariaceae). AB - Ribosomal DNA sequences for the ITS 1, 5.8S, ITS 2 and adjoining regions of the 18S and 25S were obtained from Mimulus glaucescens (Scrophulariaceae) via cloned PCR products. The spacer sequences were completely unrelated to other plant taxa, although spacer lengths were approximately the same. Interestingly, the Mimulus 5.8S sequence was much more divergent than other higher-plant rDNA sequences. Consideration of the secondary structure of the 5.8S rRNA shows that most of the changes in Mimulus are compensatory and preserve the basic secondary structure of the mature RNA molecule. PMID- 8343603 TI - Transfer RNA-mediated suppression of stop codons in protoplasts and transgenic plants. AB - We have developed a simple, rapid and sensitive assay for tRNA gene expression in plant cells. A plant tRNA(Leu) gene was site-specifically mutated to encode each of the three anticodon sequences (CUA, UUA and UCA) that recognize, respectively, the amber, ochre and opal stop codons. The suppression activity of these genes was detected by their ability to restore transient beta-glucuronidase (GUS) expression in tobacco protoplasts electroporated with GUS genes containing premature stop codons. Protoplasts co-electroporated with the amber suppressor tRNA gene and a GUS gene containing a premature amber stop codon showed up to 20 25% of the activity found in protoplasts transfected with the functional control GUS gene. Ochre and opal suppressors presented maximum efficiencies of less than 1%. This system could be adapted to examine transcription, processing or aminoacylation of tRNAs in plant cells. In addition, phenotypically normal, fertile tobacco plants expressing a stably incorporated amber suppressor tRNA gene have been obtained. This suppressor tRNA can be used to transactivate a target gene containing a premature amber stop codon by a factor of at least several hundred-fold. PMID- 8343605 TI - Inhibitory effects of human cystatin C on plum pox potyvirus proteases. AB - The effect of different protease inhibitors on the proteolytic processing of the plum pox potyvirus (PPV) polyprotein has been analyzed. Human cystatin C, an inhibitor of cysteine proteases, interfered with the autoprocessing of the viral papain-like cysteine protease HCPro. Unexpectedly, it also had an inhibitory effect on the autocatalytic cleavage of the Nla protease which, although it has a Cys residue in its active center, has been described as structurally related to serine proteases. Other protease inhibitors tested had no effect on any of the cleavage events analyzed. PMID- 8343606 TI - Isolation and characterization of cDNA clones encoding a 18.8 kDa polypeptide, the product of the gene psaL, associated with photosystem I reaction center from spinach. AB - Several cDNA clones encoding subunit XI of photosystem I reaction center (PSI-L) have been isolated from two lambda gt11 expression libraries based on polyadenylated RNA of spinach seedlings illuminated for 4 and 16 h, respectively. The precursor polypeptide made from these recombinant DNAs in vitro can be efficiently imported into isolated spinach chloroplasts. It is correctly processed to the size of the authentic polypeptide and integrates into the photosystem I assembly. The 834 nucleotide sequence of the longest cDNA insert encodes a precursor polypeptide of 24 kDa (216 residues) and a mature protein of probably 18.8 kDa (169 residues). Hydropathy analysis suggests that the polypeptide contains two transmembrane segments. The protein appears to originate in a single-copy gene in spinach and to be decoded from RNA species of ca. 900 bases. PMID- 8343607 TI - RNA editing of the barley (Hordeum vulgare) mitochondrial ATP synthase subunit 9. AB - The barley (Hordeum vulgare) FO-ATP synthase subunit 9 (atp9) was isolated from the mitochondrial DNA. Two copies of atp9 are present in barley mitochondria and 2 major transcripts of 2.7 kb and 1.2 kb were detected on RNA blots. RNA editing as C-to-U conversion occurs in barley atp9 in seven positions. Five of these seven positions lead to an amino acid change whereas two conversions are silent. The editing positions of barley were found to be identical to those of wheat. Whereas in wheat, Oenothera and Petunia all the atp9 transcripts were fully edited, 24% of the barley cDNA clones were partially edited as compared to 10% partially edited clones in wheat. PMID- 8343608 TI - Molecular cloning and sequencing analysis of a beta-tubulin gene from Lupinus albus. AB - Genomic lambda-Dash library constructed from Lupinus albus nuclear DNA was screened using a fragment of the beta-tubulin cDNA (beta 8-31) clone of Chlamydomonas reinhardtii as probe. One of the positive recombinant phages was isolated, subcloned and analysed by sequencing. We present here nucleotide and derived amino acid sequences of the beta-tubulin gene, designated as L beta 1 and identified by similarity with other beta-tubulins. The L beta 1-encoded protein reveals a very high degree of similarity with other plant tubulins and contains consensus sequences for binding guanine base, phosphate and Mg2+. Northern analysis of total RNA isolated from roots, leaves, flowers and pools revealed that Lupinus albus beta-tubulin genes are constitutively expressed in all studied plant tissues. PMID- 8343609 TI - Homology of the N-terminal domain of the petH gene product from Anabaena sp. PCC 7119 to the CpcD phycobilisome linker polypeptide. AB - The complete nucleotide sequence of the petH gene encoding ferredoxin-NADP+ reductase from the nitrogen-fixing cyanobacterium Anabaena sp. PCC 7119 has been determined. The encoded polypeptide is 136 amino acids longer than the enzyme obtained after purification to homogeneity. The extended N-terminal domain consists of 80 amino acids which shows homology to the CpcD phycobilisome linker polypeptide, through which FNR might be anchored to the thylakoid-bound phycobilisomes. A 56 amino acid interdomain fragment is found which could be a target for proteolysis. PMID- 8343610 TI - Effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. The Tolrestat Study Group. AB - Tolrestat is a well tolerated nonhydantoin aldose reductase inhibitor that has been reported to improve nerve conduction in diabetic animals and humans. Its effects on nerve biochemistry and structure have not been studied in patients with diabetic neuropathy. Patients with advanced diabetic neuropathy treated with long-term open-label tolrestat were randomly assigned to continuation on drug treatment or to placebo-controlled drug withdrawal for 12 months. At the end of this period, sural nerve biopsies were obtained for measurement of glucose, sorbitol, and fructose content, and for detailed morphometric analysis. Tolrestat ameliorated the glucose-mediated increase in sorbitol and fructose in sural nerve tissue. No statistically significant differences in nerve morphometry emerged between the two groups; however, both treatment groups exhibited increased nerve fiber regeneration and normalization of axo-glial dysfunction and segmental demyelination following long-term tolrestat treatment. These findings are similar to those previously reported in a placebo-controlled sequential nerve biopsy study with the aldose reductase inhibitor sorbinil. Thus tolrestat is a biochemically effective aldose reductase inhibitor in human diabetic nerve with potential therapeutic efficacy for diabetic neuropathy. PMID- 8343611 TI - Withdrawal of the aldose reductase inhibitor tolrestat in patients with diabetic neuropathy: effect on nerve function. The Tolrestat Study Group. AB - A double-blind, placebo-controlled clinical trial was conducted to study the effects of discontinuing tolrestat, an aldose reductase inhibitor, on peripheral sensorimotor diabetic neuropathy. After an average of 4.2 years of continuous tolrestat use, 372 patients were randomly assigned to either placebo or continued tolrestat therapy and were followed for 52 weeks. After 3 months, patients who perceived worsening of symptoms of neuropathy were allowed to switch once to the alternate treatment group while maintaining the double-blind. Patients assigned to placebo had significant deterioration in motor nerve conduction velocity (MNCV) while those maintained on tolrestat did not (p < 0.05). The 28 patients who were randomly assigned to tolrestat and elected to switch to placebo had a significant deterioration in MNCV while the 36 assigned to placebo who switched to tolrestat had a significant improvement (p < 0.05). Treatment differences in favor of tolrestat were observed for sensation in the toes as well as for pain (p < 0.05). These data indicate that withdrawal from long-term treatment with tolrestat has a detrimental effect on several measures of diabetic neuropathy, whereas continuation of treatment is associated with stabilization of these measures, suggesting a continued role for polyol pathway activity in late neuropathy. PMID- 8343612 TI - Human kidney aldose and aldehyde reductases. AB - Mounting experimental evidence links increased aldose reductase activity with diabetes-related kidney functional changes. To investigate the interrelationship of NADPH-dependent reductases in the human kidney, both aldose reductase and aldehyde reductase were purified from human kidney by a series of chromatographic procedures, including gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A, and chromatofocusing on Mono P. Each purified enzyme appeared as a single band on polyacrylamide gel after electrophoresis or isoelectric focusing. Aldose reductase has a pI of 5.7 and apparent molecular weight of 37 kDa, calculated from SDS-polyacrylamide gel electrophoresis, while aldehyde reductase has a pI of 5.2 and molecular weight of 39 kDa. Similar molecular weights were also obtained by gel filtration, indicating that both aldose and aldehyde reductases are present as monomers in the human kidney. Aldehyde reductase is primarily localized in the cortex, while the medulla contains aldose reductase. Both enzymes displayed properties consistent with the general characteristics of aldose and aldehyde reductases obtained from either rat or dog kidney. Purified aldose reductase utilizes aldose sugars such as D xylose, D-glucose, and D-galactose as substrates while aldehyde reductase preferentially reduces D-glucuronate and oxidizes L-gulonate to D-glucuronate. Despite the lower apparent affinity of aldehyde reductase for aldose sugars (approximately 20- to 100-fold less) both enzymes reduced D-xylose, D-glucose, and D-galactose to their respective sugar alcohols in in vitro incubation studies where the generated sugar alcohols were identified by gas chromatography. Both enzymes were also inhibited by aldose reductase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343613 TI - Dietary myo-inositol supplementation does not prevent retinal and glomerular vascular structural changes in chronically diabetic rats. AB - To assess effects of dietary myo-inositol supplementation on diabetes-induced vascular structural lesions, diabetes was induced in Sprague-Dawley rats with streptozotocin; one-third of these rats was fed a 2% myo-inositol diet for 9 months, one-third was left untreated for 5 months then treated with myo-inositol for the last 4 months, and one-third was untreated for the entire 9 months. Controls included untreated and myo-inositol-treated groups. Weight gain was impaired and plasma glucose, glycosylated hemoglobin, food consumption, urine volume, and albuminuria were increased significantly in diabetic versus age matched control rats. Plasma myo-inositol levels were increased approximately fivefold in controls and approximately six- to eightfold in diabetic rats treated with myo-inositol. In general, myo-inositol did not affect any of the above parameters in control or diabetic rats. Retinal capillary basement membrane width (CBMW) was increased significantly (approximately 50% versus controls) after 9 months of diabetes. In the control group myo-inositol increased CBMW to the level of untreated diabetic rats; myo-inositol had no effect on CBMW in each diabetic group. The number of retinal capillaries containing pericyte nuclei and pericyte capillary coverage were increased in untreated as well as myo-inositol-treated diabetic rats and in the myo-inositol-treated control group. Glomerular CBMW was increased after 5 and 9 months of diabetes versus age-matched controls, and was increased even more by myo-inositol. Mesangial fractional volume of the glomerulus was increased 36% by diabetes and was decreased slightly but significantly by myo-inositol. These results indicate that diets supplemented with 2% myo-inositol (1) cause capillary basement membrane (CBM) thickening and pericyte changes in retinal capillaries of normal rats, (2) are ineffective in preventing or reversing diabetes-induced retinal CBM thickening, and (3) cause further thickening of glomerular CBM in diabetic rats. PMID- 8343614 TI - Prospective study of the enzymatic activities in urine of N-acetyl-beta-D glucosaminidase, alpha-D-mannosidase, alpha- and beta-D-glucosidases, alpha-L- and beta-D-fucosidases, and beta-D-galactosidase in type I diabetes mellitus with early nephropathy. AB - Different surveys have been carried out on the plasma activities of different glycosidases in patients with insulin-dependent diabetes mellitus, but research on urinary glycosidases in this disease is scanty and incomplete. To elucidate the behavior of these lysosomal enzymes in the metabolic alterations occurring in the glomerular basal membrane during the initial stages of diabetic nephropathy, we conducted a prospective study to examine the urinary activities of N-acetyl beta-D-glucosaminidase (NAG), alpha-D-mannosidase, alpha- and beta-D-glucosidase, alpha-L- and beta-D-fucosidase, and beta-D-galactosidase in patients with type I insulin-dependent diabetes mellitus, surveyed over 18 months, whose early diabetic nephropathy was detected by the presence of microalbuminuria. The simultaneous determination of beta 2-microglobulin in urine confirmed the glomerular origin of the albuminuria. No statistically significant correlation was found between the levels of albuminuria and the activities of any of the glycosidases analyzed. In the diabetic patients, a significant decrease was observed in the activities of all the enzymes (p < 0.05), except NAG and alpha-D mannosidase, although the decrease in the latter was very close to statistical significance (p = 0.028, unilateral; p = 0.057 bilateral). Similarly, in the patients, there was a significant negative correlation (p < 0.05) with the serum levels of fructosamine, except with beta-D-galactosidase, which showed a positive correlation (p < 0.05) with fructosamine and blood HbA1c.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343615 TI - Diabetic embryopathy: a selective review of recent trends. PMID- 8343616 TI - The role of myoglobin in retarding oxygen depletion in skeletal muscle. AB - Myoglobin retards the development of anoxia in a poorly perfused region of skeletal muscle by facilitating diffusion into this region from adjacent normally perfused regions and by releasing bound oxygen directly into the tissue. We examine these phenomena by analyzing a mathematical model of time-dependent myoglobin-facilitated oxygen transport. The governing equations are solved using similarity transformations and multiple-scale techniques. We find that when perfusion of a region is suddenly decreased, oxygen depletion is significantly retarded by direct release of myoglobin-bound oxygen into the tissue and that myoglobin-facilitated diffusion of oxygen from adjacent regions becomes significant at very low oxygen concentration. PMID- 8343617 TI - On the distribution of vaccine protection under heterogeneous response. AB - We assume that individuals in a vaccinated cohort respond heterogeneously and acquire a continuous spectrum of effective protection against an environmental exposure to infection that can be varying in time. The notion of dynamical invariants is applied to a proportional hazard model with an unvaccinated or placebo cohort as baseline. The hazard is expressed as a susceptibility factor times a measure of environmental exposure to infection. Using the time-evolving information for the aggregated vaccinated cohort and the unvaccinated cohort, it is possible to reconstruct the distribution of effective protection imparted by the vaccination at the beginning of observation. Efficacy is defined in terms of the hazard ratio at the beginning of observation. PMID- 8343618 TI - Nonlinear control of biotechnological processes with growth-production decoupling. AB - Nonlinear control design techniques for a class of continuous biological processes with growth and production decoupling are investigated. We establish, under realistic assumptions on the kinetics, that though neither the inlet substrate concentration nor the dilution rate can achieve linearization of the global dynamics, we can maximize the dimension of the linear system obtained after feedback and get stable zero dynamics by choosing output functions having a physical meaning. More precisely, if the manipulated variable is the inlet substrate concentration, then the output can be chosen as the biomass concentration. But if the chosen input is the dilution rate, then a suitable output corresponds to yields. PMID- 8343619 TI - Conditioning a diffusion at first-passage and last-exit times, and a mirage arising in drug therapy for HIV. AB - Let X(t), t > or = 0, be a real-valued diffusion process, not necessarily time homogeneous. For a fixed z, let Tz be the first-passage time to z; and, under the assumption that z is a transient state, let Vz be the last-exit time from z. The main results of this work are a description of the structure of X(t), t > or = 0, upon conditioning by the values of Tz and Vz, and some of the characteristics of the conditioned process. The results are illustrated by application to Brownian motion with constant drift and also to the Ornstein-Uhlenbeck process augmented by a linear term representing a constant drift (a nonhomogeneous diffusion). The problem was motivated by the need to explain a possible mathematical mirage in the testing of antiviral drugs for HIV infection. PMID- 8343621 TI - The future of health care in the United Kingdom. PMID- 8343620 TI - Effect of red blood cell shape on oxygen transport in capillaries. AB - A mathematical model of oxygen (O2) transport within a capillary utilizes axisymmetric red blood cell (RBC) shapes that were predicted theoretically by Zarda et al. in 1977. Chemical kinetics and both free and facilitated diffusion of O2 are accounted for in this time-dependent model. The finite-element method is used to solve the governing partial differential equations. It is found that the shape of RBCs, characterized by the shape parameter theta adapted from Zarda et al., affects such important O2 transport characteristics as capillary wall O2 flux and hemoglobin (Hb) saturation. At an RBC residence time (time for an RBC to travel from the capillary inlet to a given point) of 0.22 s, a change in the shape parameter theta from 0 (undeformed cell) to 26 (parachute-shaped cell) decreases the spatially averaged O2 flux by 26%. The dependence of O2 flux on RBC shape diminishes as the RBC residence time increases. The difference in Hb saturation at the RBC residence time of 0.22 s can be as large as 10% for different values of theta. The mass transfer Nusselt number, which is inversely proportional to transport resistance, decreases with increases in theta. The fractional transport resistance in the plasma region accounts for approximately 65-80% of the total intracapillary resistance. Calculations show that local chemical equilibrium in the O2-Hb chemical reaction is attained everywhere except within a thin boundary layer adjacent to the erythrocyte membrane, where significant deviation from chemical equilibrium occurs. PMID- 8343622 TI - Sex selection. PMID- 8343623 TI - Biochemical screening for Down's syndrome. PMID- 8343624 TI - Trials and errors. PMID- 8343626 TI - London specialty reviews. PMID- 8343625 TI - How can doctors diagnose colorectal cancer earlier? PMID- 8343627 TI - Can paternal preconceptional radiation account for the increase of leukaemia and non-Hodgkin's lymphoma in Seascale? AB - OBJECTIVE: To determine if the excess of leukaemia and non-Hodgkin's lymphoma in Seascale is restricted to those born in the parish and whether it might be explained by the postulated relation with paternal preconceptional radiation. DESIGN: Comparison, separately for those born in the parish and those born elsewhere, of the numbers of these malignancies observed in Seascale with those expected on the basis of reference rates for England and Wales. Details of paternal radiation levels were sought for each case. SETTING: The parish of Seascale in west Cumbria. SUBJECTS: Residents of Seascale below age 25 years in the years 1951-91. MAIN OUTCOME MEASURES: The observed and expected numbers of cases of leukaemia and non-Hodgkin's lymphoma within Seascale among those born there and among those born elsewhere. Also, the levels of any paternal preconceptional radiation associated with each case. RESULTS: A significant excess of leukaemia and non-Hodgkin's lymphoma at ages 0-24 was found in Seascale in those who were born there (ratio of observed to expected cases 8.6 and 20.2 respectively; p < 0.01). This also applied to those not born there (7.2 and 16.5; p < 0.01), a group often regarded as not showing an excess. The estimates were then conservatively recalculated so as to overestimate the risks among those born in Seascale and underestimate them among those born elsewhere. On this basis the six cases in those born in Seascale compare with 0.38 expected (15.8; p < 0.001), of which two were associated with paternal preconceptional life-time levels of 100 mSv or greater and three others with levels of 90-99 mSv. Among those born elsewhere, there were five cases (expected 0.74; ratio 6.7, p < 0.01), of which only one was associated with a high level of such radiation. CONCLUSIONS: Paternal preconceptional radiation cannot be the sole cause of the excess in Seascale since it will not explain the excess among those born outside Seascale. It follows that, unless two causes are to be postulated, any single cause must be a factor other than paternal preconceptional radiation. On this basis, the association found among those born there, if not partly due to chance, may reflect an indirect relation with the true cause. The recent hypothesis about such paternal radiation has originated in a subgroup of the excess cases that have aroused concern. PMID- 8343628 TI - Is screening and intervention for microalbuminuria worthwhile in patients with insulin dependent diabetes? AB - OBJECTIVE: To analyse the cost-benefit of screening for and antihypertensive treatment of early renal disease indicated by microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN: Previously published data were used to estimate transition probabilities for each step from normoalbuminuria until death. The effect of intervention on urinary albumin excretion rate by antihypertensive treatment was arbitrarily set at three different levels. All direct costs (screening, antihypertensive treatment, treatment of end stage renal failure) were included in the cost-benefit analysis by using real discount rates of 2.5% and 6%. SETTING: Computer simulation. SUBJECTS: Simulated cohort of 8000 patients. MAIN OUTCOME MEASURES: Mortality, incidence of diabetic nephropathy, incidence of end stage renal failure, and costs versus savings. RESULTS: Assuming treatment effects of 33% and 67% median life expectancy increased by four to 14 years, respectively, and the need for dialysis or transplantation decreased by 21% to 63%. Costs and savings would balance if the annual rate of increase of albuminuria was decreased from 20% to 18% a year. CONCLUSIONS: Screening and intervention programmes are likely to have life saving effects and lead to considerable economic savings. PMID- 8343629 TI - Site of principal metabolic defect in idiopathic haemochromatosis: insights from transplantation of an affected organ. PMID- 8343630 TI - Increased concentrations of serum lipoprotein (a) in response to growth hormone treatment. PMID- 8343631 TI - Explaining variations in prescribing costs across England. AB - OBJECTIVE: To derive a predictive model for national prescribing behaviour in terms of basic morbidity and demographic factors. DESIGN: 24 demographic, morbidity, and practice factors were entered into a multiple regression analysis to determine the net ingredient cost per patient. SETTING: The 90 family health service authorities in England for 1989. RESULTS: For net ingredient cost per patient only two demographic factors (numbers of pensioners and the mobility of the registered population measured by list inflation) and two morbidity related factors (standardised mortality ratios and numbers of prepayment certificates issued) significantly contributed to a multiple regression model. This model explained 81% of the variation in net ingredient cost per registered patient between family health services authorities. The model also enabled a weighting factor of 4.6 (95% confidence interval 3.2 to 6.7) to be derived for the net ingredient cost for elderly patients (compared with the existing prescribing unit factor of 3). CONCLUSIONS: The model shows that variations in prescribing costs essentially reflect demand. It also suggests that the current prescribing unit value of 3 for patients aged 65 or more underestimates the extra costs of prescribing for elderly patients. PMID- 8343633 TI - Leave practice. PMID- 8343632 TI - Contraceptives, counselling, and pregnancy in women with sickle cell disease. AB - Sickle cell disease is listed in the manufacturers' data sheets in the United Kingdom as a contraindication to the use of most combined contraceptive pills; the result is confused advice on family planning to a group of women who are at substantial risk from both planned and unplanned pregnancy. A study in north London on the use of contraceptives by women with sickle cell disease indicates that the use of combined oral contraceptives is common. Although medical staff usually advised against pregnancy, such advice was almost always ignored. Over half of the women surveyed had some knowledge about antenatal diagnosis. Family planning advice should be an integral part of the care of women with sickle cell disease. In the absence of specific data to the contrary all methods of contraception may be considered, although with appropriate caution. PMID- 8343634 TI - The first 15 cm are important in upper gastrointestinal endoscopy. PMID- 8343635 TI - Dispensing in general practice. Overhaul system of reimbursement. PMID- 8343636 TI - Dispensing in general practice. Criticisms unfounded. PMID- 8343637 TI - Dispensing in general practice. NHS regulations deny patients cheap drugs. PMID- 8343638 TI - Dispensing in general practice. Dispensing improves compliance. PMID- 8343639 TI - Teenage pregnancy. Give girls a motive for avoiding it. PMID- 8343641 TI - Teenage pregnancy. Seek the views of teenagers. PMID- 8343640 TI - Open access gastroscopy. Service is efficient and effective. PMID- 8343642 TI - Open access gastroscopy. GPs use gastroscopy appropriately. PMID- 8343643 TI - Accident and emergency in London. Patients' perceptions are the problem. PMID- 8343644 TI - Accident and emergency in London. Good primary care reduces workload. PMID- 8343645 TI - Treating hyperhidrosis. Complications of endoscopic sympathectomy. PMID- 8343646 TI - Treating hyperhidrosis. Reserve sympathectomy for palmar hyperhidrosis. PMID- 8343647 TI - Child health surveillance. PMID- 8343648 TI - Antenatal HIV testing may put pressure on women. PMID- 8343649 TI - Chickenpox in pregnancy. PMID- 8343650 TI - Reduction in infant mortality probably due to fall in cot deaths. PMID- 8343651 TI - Do we need more hospices? PMID- 8343652 TI - Infection control in dentistry. PMID- 8343653 TI - The new NHS. Britain hasn't learnt from America's mistakes. PMID- 8343654 TI - The Calman report and specialist training. More questions, no answers. PMID- 8343655 TI - The Calman report and specialist training. Calman report builds on the status quo. PMID- 8343656 TI - The Calman report and specialist training. Government must meet the cost. PMID- 8343657 TI - The Calman report and specialist training. European certificates don't mean the same. PMID- 8343658 TI - Subcortical dementia. PMID- 8343659 TI - Does routine ultrasound scanning improve outcome in pregnancy? Meta-analysis of various outcome measures. AB - OBJECTIVE: To evaluate the effectiveness of routine ultrasound scanning in pregnancy by a meta-analysis of various outcome measures. DESIGN: Meta-analysis of randomised controlled trials evaluating the effect of routine ultrasound scanning on perinatal mortality and morbidity. Live birth rate (that is, live births per pregnancy) is included as a measure of pregnancy outcome in addition to the conventional perinatal mortality. SUBJECTS: 15,935 pregnancies (7992 in which routine ultrasound scanning was used and 7943 controls with selective scanning) from four randomised controlled trials. MAIN OUTCOME MEASURES: Perinatal mortality, live birth rate, rate of miscarriage, Apgar score < 7 at 1 minute, and number of induced labours. RESULTS: The live birth rate was identical in both screening and control groups (odds ratio = 0.99; 95% confidence interval 0.88 to 1.12) although the perinatal mortality was significantly lower in the group who had routine ultrasonography (0.64, 0.43 to 0.97). Differences in perinatal morbidity between the two groups as measured by the proportion of newborn babies with Apgar score < 7 at 1 minute were not significant (1.05; 0.93 to 1.19). CONCLUSION: Routine ultrasound scanning does not improve the outcome of pregnancy in terms of an increased number of live births or of reduced perinatal morbidity. Routine ultrasound scanning may be effective and useful as a screening for malformation. Its use for this purpose, however, should be made explicit and take into account the risk of false positive diagnosis in addition to ethical issues. PMID- 8343660 TI - Breast feeding and risk of breast cancer in young women. United Kingdom National Case-Control Study Group. AB - OBJECTIVE: To investigate whether breast feeding is related to subsequent risk of breast cancer. DESIGN: Population based case-control study designed primarily to investigate the relation between oral contraceptives and risk of breast cancer; data obtained from questionnaires administered by interviewers, general practitioner notes, and family planning clinic records. SETTING: 11 health regions in Britain. SUBJECTS: Women diagnosed with breast cancer before age 36 living in the defined study areas. One control per case, matched for age, was selected from the list of the case's general practitioner. 755 case-control pairs were interviewed. MAIN OUTCOME MEASURES: Duration of breast feeding each liveborn infant; timing of return of menses; hormone use; other risk factors for breast cancer. RESULTS: Risk of breast cancer fell with increasing duration of breast feeding (relative risk = 0.94 per three months' breast feeding; test for trend p = 0.026) and with number of babies breast fed (relative risk = 0.86; test for trend, p = 0.017). Breast feeding each baby for longer than three months conferred no additional benefit. Breast feeding was more strongly negatively associated with risk of breast cancer than duration of postpartum amenorrhoea (chi 2 test for trend, p = 0.69). Hormonal suppression of lactation was unrelated to risk of breast cancer (relative risk = 0.96 per episode of suppressed lactation; test for trend, p = 0.72). CONCLUSIONS: These results suggest that breast feeding protects against the development of breast cancer in young women. PMID- 8343661 TI - Sex, pregnancy, hormones, and melanoma. PMID- 8343662 TI - Factors associated with lack of awareness of HIV infection before diagnosis of AIDS. AB - OBJECTIVE: To identify characteristics of people likely to be unaware of their HIV infection before diagnosis of AIDS defining disease. DESIGN: Survey of continuing surveillance of voluntarily reported AIDS cases. SUBJECTS: 4127 adults with AIDS diagnosed during 1989-92 and reported to the Public Health Laboratory Service AIDS Centre. SETTING: England and Wales. MAIN OUTCOME MEASURE: Lack of prolonged awareness of infection before diagnosis of AIDS, defined as an interval of nine months or less between first positive test result and diagnosis of AIDS. RESULTS: Of 3556 adults with known dates of first positive HIV test result and AIDS diagnosis, 1742 (49%) had been unaware of their infection for up to nine months before AIDS was diagnosed. Lack of awareness was independently and positively associated with infection through heterosexual contact (odds ratio 4.46, 95% confidence interval 3.15 to 6.33), AIDS reported outside the Thames regions (1.64, 1.38 to 1.96), and being non-white (1.99, 1.51 to 2.61). Women were less likely to be unaware than men (0.50, 0.33 to 0.76), and people diagnosed in 1992 were least likely to be unaware (0.48, 0.39 to 0.60). Those aged 25-49 years at diagnosis were less likely to be unaware than those aged 15 24 years and those aged 50 and over. CONCLUSIONS: People with certain characteristics are more likely than others to be unaware of their HIV infection before AIDS is diagnosed and are therefore less likely to receive prophylaxis. Methods for educating this heterogeneous group need to be investigated. PMID- 8343663 TI - Peak expiratory flow rate in schoolchildren living close to Braer oil spill. PMID- 8343664 TI - Teenagers, sex, and risk taking. PMID- 8343665 TI - Death from pulmonary microembolisation after intravenous injection of temazepam. PMID- 8343666 TI - Josamycin-induced pedal oedema. PMID- 8343667 TI - Taste disorders and terbinafine. PMID- 8343668 TI - Effects of preventive home visits to elderly people. AB - OBJECTIVES: To assess the effect of preventive home visits by public health nurses on the state of health of and use of services by elderly people living at home. DESIGN: Randomised controlled trial. SETTING: General population of elderly people in one of the southern regions of the Netherlands. SUBJECTS: 580 subjects aged between 75 and 84 years randomly allocated to intervention (292) or control (288) group. INTERVENTIONS: Four visits a year over three years in intervention group. Control group received no home visits. MAIN OUTCOME MEASURES: Self rated health, functional state, well being, loneliness, aspects of the mental state (depressive complaints, memory disturbances), and mortality. Use of services and costs. RESULTS: Visits had no effect on the health of the subjects. In the group visited no higher scores were seen on health related measures, fewer died (42 (14%) v 50 (17%)), and community care increased slightly. In the control group more were referred to outpatient clinics (166 (66%) v 132 (55%)), and they had a 40% increased risk of admission (incidence rate ratio 1.4; 90% confidence interval 1.2 to 1.6). No differences were found in long term institutional care, and overall expenditure per person in the intervention group exceeded that in the control group by 4%. Additional analyses showed that visits were effective for subjects who initially rated their health as poor. CONCLUSIONS: Preventive home visits are not beneficial for the general population of elderly people living at home but might be effective when restricted to subjects with poor health. PMID- 8343670 TI - Accuracy of diagnosis of psychosis on general practice computer system. AB - OBJECTIVES: To determine the accuracy of diagnoses of schizophrenia and non affective psychosis entered by general practitioners on a computer system. To compare recording of clinical events on computer with written records. DESIGN: Examination of case notes of all patients with a computer diagnosis of psychosis. Search of 8000 randomly selected patient records to identify patients with psychosis not recorded on computer and comparison of 141 computer and written entries for prescribing and consultation in each practice. SETTING: 13 London practices on the VAMP research bank. MAIN OUTCOME MEASURES: Accuracy of record of psychosis compared with ICD 9, American Psychiatric Association diagnostic manual, and syndrome checklist criteria. RESULTS: Computer search revealed 102 patients with schizophrenia, 78 with other psychoses, and 71 with non-affective psychosis who had adequate case notes. The sensitivity and positive predictive value of the computer diagnosis of schizophrenia were 88% (95% confidence interval 62% to 98%) and 71% (48% to 88%). For all non-organic psychoses sensitivity was 91% (74% to 97%) and positive predictive value was 91% (74% to 98%). On average 95% of all known prescriptions and 74% of all consultations were recorded on computer compared with 42% and 75% in written records. CONCLUSIONS: Recording of psychotic illness on the VAMP computer is accurate and complete. Prescribing was more fully recorded on the computer than on the written records. Computer databases of well motivated general practitioners could be used for research. PMID- 8343669 TI - Adhesion and the cancer jigsaw. PMID- 8343671 TI - Searching for gastrinomas. PMID- 8343672 TI - Structural adjustment: the wrong prescription for Africa? PMID- 8343673 TI - Health, humanitarian relief, and survival in former Yugoslavia. AB - Since the World Health Organisation's effort in former Yugoslavia started in July 1992 it has been concerned with the public health policies of survival. It has provided advice to the United Nations High Commission for refugees, helped the voluntary agencies coordinate their work, assessed health needs, and provided practical help in the field to all parties to the conflict. Three features of the Bosnia war have particularly deplorable effects on health: ethnic cleansing, deliberate attacks on hospitals, and systematic rape. The WHO's response has included initiatives in nutrition, winter survival, and medical supplies. This experience shows that the WHO can have a useful role complementary to that of other agencies in situations where the basic elements for survival of the population are seriously compromised by war. PMID- 8343675 TI - Reviewing the NHS review. PMID- 8343674 TI - Chloroquine poisoning. Rapidly fatal without treatment. PMID- 8343676 TI - ABC of one to seven. Audit in primary care paediatrics. PMID- 8343677 TI - Caring for patients with brain injuries. ...and neuropsychiatrists. PMID- 8343678 TI - Caring for patients with brain injuries. The role of rehabilitation specialists... PMID- 8343679 TI - Caring for patients with brain injuries. Towards a better service. PMID- 8343680 TI - Control of communicable disease. A problem shared. PMID- 8343681 TI - Control of communicable disease. Compulsory removal powers inappropriate. PMID- 8343682 TI - Control of communicable disease. Misfits in the new NHS. PMID- 8343683 TI - Control of communicable disease. Tuberculosis screening falls foul of reforms. PMID- 8343684 TI - Control of communicable disease. Departments of microbiology are central to control of infection. PMID- 8343685 TI - Control of communicable disease. Government ignores control of viruses. PMID- 8343686 TI - Child health services. Should be combined. PMID- 8343687 TI - Homosexuality in the US. PMID- 8343688 TI - Use computers to detect inappropriate prescriptions. PMID- 8343689 TI - Residential and nursing care in London. Hampering discharge from acute units. PMID- 8343690 TI - Residential and nursing care in London. Number of places is decreasing... PMID- 8343691 TI - Chlamydial respiratory infections. Don't get bogged down by differentiating species. PMID- 8343692 TI - Tuberculosis is increasing in England and Wales. PMID- 8343693 TI - Epidural analgesia during childbirth. Minimising headache after dural puncture. PMID- 8343694 TI - Epidural analgesia during childbirth. Association with backache is real. PMID- 8343695 TI - Psychiatric services for elderly people. GPs happy with multidisciplinary teams. PMID- 8343696 TI - Psychiatric services for elderly people. Traditional model has limited scope. PMID- 8343697 TI - Hyponatraemia following desmopressin. PMID- 8343698 TI - Learning to cope with violence in the workplace. PMID- 8343699 TI - Screening for cardiovascular risk factors. PMID- 8343701 TI - Searching the literature. Be systematic in your searching. PMID- 8343700 TI - Neonatal intensive care. Staff must be experienced. PMID- 8343702 TI - Induction of labour. PMID- 8343703 TI - Will it hurt, doctor? Factors predicting patients' experience of pain during double contrast examination of the colon. PMID- 8343704 TI - Developing organisational vision in general practice. AB - Vision is a fashionable but ill defined term in management circles. Nevertheless, it embodies a significant concept related to guiding an organisation from present realities, through opportunities and hazards, to a viable future. Until recently a typical general practice could assume a stable external environment, but now it is caught up in the uncertainties stemming from the NHS reforms. For such a practice to undertake effective strategic planning it will have to develop a vision connecting the present with aspirations for the future. While vision is usually considered to be an individual talent, it is possible to develop a collective organisational vision within a general practice, and the small size of general practices makes this relatively easy. The vision needs to be broad; it needs to be continuous; and its capacity to predict the future needs to be monitored. PMID- 8343705 TI - Patients with fatigue in general practice: a prospective study. AB - OBJECTIVE: To describe the characteristics of patients attending their general practitioners and complaining of fatigue or being "tired all the time." DESIGN: Prospective study of cohort aged 16 years and older with follow up at two weeks and by questionnaires at two and six months. SUBJECTS: 220 patients (164 women) with mean age 43 years and an age-sex matched comparison group. SETTINGS: Doctors and patients in four practices in Lancashire, Mid Glamorgan, Suffolk, and Surrey. MAIN OUTCOME MEASURES: General clinical data, results from standard group of laboratory tests, fatigue questionnaire, and 12 item general health questionnaire. RESULTS: Over twice as many patients with fatigue had high scores on the health questionnaire compared with the comparison group (156 (75%) v 69 (34%)). Results of laboratory tests were abnormal and contributed to the diagnosis in 19 patients. 59 out of 102 patients who responded had high fatigue scores six months later. Patients with persistent fatigue were more likely to have a history of anxiety or depression and to have had fatigue for more than three months on entry to the study. CONCLUSIONS: Women are particularly at risk of fatigue. The outcome is better if patients have had symptoms for three months or less or there is no history of emotional illness. PMID- 8343706 TI - Management of raised blood pressure in New Zealand: a discussion document. AB - A report to the National Advisory Committee on Core Health and Disability Support Services, New Zealand, on the management of raised blood pressure recommends that decisions to treat raised blood pressure should be based primarily on the estimated absolute risk of cardiovascular disease rather than on blood pressure alone. In general, patients with a blood pressure of 150-170 mm Hg systolic or 90 100 mm Hg diastolic, or both, should be given treatment to lower blood pressure if the risk of a major cardiovascular disease event in 10 years is more than about 20%. The results of clinical trials indicate that, at this level of absolute risk, 150 people would require treatment to reduce the annual number of cardiovascular events by about one. Implementation of these recommendations may result in a smaller proportion of people aged under 60, particularly women, receiving treatment but an increased proportion of older people treated. In the absence of specific contraindications, low dose diuretics and low dose beta blockers should be considered for first line treatment, since for only these drug groups is there direct evidence of reduced risk of stroke and coronary disease in people with raised blood pressure. PMID- 8343707 TI - Health professionals and South Africa: supporting change in the health sector. AB - Now that political change is on the way in South Africa, what should be the position of doctors who are invited to visit the country? Does the "academic boycott" still have relevance? Waterston and Zwi review the case for and against an academic boycott policy, using evidence collected during the recent visit by Physicians for Human Rights (UK) and the Johannes Wier Foundation. The health system in South Africa is still inequitable, and despite progress towards desegregation in hospitals there is little momentum towards universal provision of primary health care, especially in the rapidly growing townships around big cities. The authors consider that pressure on the government should be maintained by outside organisations but that support directed towards appropriate health care should be encouraged, particularly in public health and primary health care. PMID- 8343708 TI - Guidelines for the management of spontaneous pneumothorax. Standards of Care Committee, British Thoracic Society. AB - Simple flow diagrams, with explanatory notes, have been devised to assist in the immediate and subsequent management of patients presenting to casualty departments with spontaneous pneumothorax. They cover decision making about which patients require admission; whether a drainage procedure is necessary; if so, the appropriate method, including technical details; inpatient treatment; referral of inpatients to a respiratory specialist; and follow up arrangements. The guidelines, designed for incorporation into casualty and ward handbooks, have already proved valuable in several district general hospitals, and can be used as a basis for audit. PMID- 8343709 TI - ABC of one to seven. Services for children: primary care. PMID- 8343710 TI - The Hawksley random zero sphygmomanometer. Manufacturer fights back. PMID- 8343711 TI - The Hawksley random zero sphygmomanometer. Should be abandoned. PMID- 8343712 TI - The Hawksley random zero sphygmomanometer. Don't condemn it without proper evidence. PMID- 8343713 TI - The Hawksley random zero sphygmomanometer. Instrument is accurate if used properly. PMID- 8343714 TI - The Hawksley random zero sphygmomanometer. Used in epidemiology, not individual people. PMID- 8343715 TI - Measuring patients' views of their health. SF 36 misses the mark. PMID- 8343716 TI - Reducing serum cholesterol. Confusion remains over whom to treat. PMID- 8343717 TI - Reducing serum cholesterol. Lower cholesterol of doubtful benefit to anyone. PMID- 8343719 TI - Measuring patients' views of their health. Definitions of health status should be rationalised. PMID- 8343718 TI - Measuring patients' views of their health. Reliability of SF 36 remains uncertain. PMID- 8343720 TI - Measuring patients' views of their health. The term outcome is ambiguous. PMID- 8343721 TI - Diagnosing meningococcal infection. Don't delay giving antibiotics. PMID- 8343722 TI - Medical angiologists. Europe already has them. PMID- 8343723 TI - Access to heart surgery for smokers. Persuade smokers to give up before surgery. PMID- 8343724 TI - Access to heart surgery for smokers. Rationed services should go to those who benefit. PMID- 8343725 TI - Patients' satisfaction with psychiatric care. PMID- 8343726 TI - Teaching communication skills. Putting it on paper helps patient understanding. PMID- 8343727 TI - The lasting trauma of the concentration camps. PMID- 8343728 TI - The health of the nation's research and development. PMID- 8343729 TI - Hand transmitted vibration. PMID- 8343730 TI - Nursing elderly patients out of bed. PMID- 8343731 TI - Private health care: patients' beliefs and practice. PMID- 8343732 TI - Whither health care in South Africa? PMID- 8343733 TI - US government is more giving on AIDS. PMID- 8343734 TI - Administration of vitamin K to newborn infants and childhood cancer. AB - OBJECTIVES: To investigate whether childhood cancer is associated with intramuscular administration of vitamin K to newborn infants. DESIGN: Routines for administration of vitamin K to infants born after normal deliveries during 1973-89 were obtained from maternity hospitals. Occurrence of cancer up to the end of 1991 was identified by comparing these records with the national cancer registry. Adherence to the routine method of administering vitamin K was checked with the medical records of a sample of 396 infants (196 who had developed childhood cancer and 200 controls). SETTING: All maternity hospitals in Sweden. SUBJECTS: 1,384,424 full term infants born after non-instrumental deliveries, 1,085,654 of whom were born in units where vitamin K was routinely given by intramuscular injection and 272,080 of whom were born where it was given orally. MAIN OUTCOME MEASURES: Odds ratios for cancer after intramuscular administration of vitamin K versus oral administration after stratification for year of birth. RESULTS: Adherence to routine method of administering vitamin K was 92% in the 235 cases where individual information could be found. The risk of cancer after intramuscular administration of vitamin K was not elevated compared with that after oral administration: odds ratios of 1.01 (95% confidence interval 0.88 to 1.17) for all childhood cancers and 0.90 (0.70 to 1.16) for childhood leukaemia. CONCLUSIONS: The alleged association between intramuscular vitamin K prophylaxis to newborn infants and childhood cancer could not be verified in the present study of full term infants born after non-instrumental delivery. PMID- 8343735 TI - Insulin resistance in offspring of hypertensive parents. AB - OBJECTIVE: To determine if insulin resistance is present in normotensive adults at increased risk of developing hypertension. DESIGN: Normotensive subjects with at least one hypertensive parent were paired with offspring of normotensive parents (controls), being matched for age, sex, social class, and physical activity. SETTING: Outpatient clinic. SUBJECTS: 30 paired subjects (16 men and 14 women) with and without a family history of hypertension, aged 18-32, with a body mass index < 25 kg/m2, with blood pressure < 130/85 mm Hg, and not taking drugs. INTERVENTIONS: Euglycaemic glucose clamp (two hour infusion of insulin 1 mU/kg/min) and intravenous glucose tolerance test (injection of 100 ml 20% glucose). MAIN OUTCOME MEASURES: Insulin mediated glucose disposal and insulin secretion. RESULTS: The offspring of hypertensive parents had slightly higher blood pressure than did the controls (mean 117 (SD 6) v 108 (5) mm Hg systolic, p = 0.013; 76 (7) v 67 (6) mm Hg diastolic, p = 0.017). Their insulin mediated glucose disposal was lower than that of controls (29.5 (6.5) v 40.1 (8.6) mumol/kg/min, p = 0.002), but, after adjustment for blood pressure, the difference was not significant (difference 6.9 (95% confidence interval -1.5 to 15.3), p = 0.10). Insulin secretion in the first hour after injection of glucose was slightly but not significantly higher in the offspring of hypertensive patients (9320 (5484) v 6723 (3751) pmol.min/l). The two groups had similar concentrations of plasma glucose (5.2 (0.3) v 5.1 (0.4) mmol/l), serum cholesterol (4.4 (0.8) v 4.6 (0.8) mmol/l), serum triglyceride (0.89 (0.52) v 0.68 (0.27) mmol/l), and serum low density lipoprotein cholesterol (2.81 (0.65) v 2.79 (0.61) mmol/l). The offspring of hypertensive parents, however, had lower serum concentrations of high density lipoprotein cholesterol (1.24 (0.31) v 1.56 (0.35) mmol/l, p = 0.002) and higher serum concentrations of non-esterified fatty acids (0.7 (0.4) v 0.4 (0.4) mmol/l, p = 0.039). CONCLUSIONS: Young normotensive subjects who are at increased risk of developing hypertension are insulin resistant. PMID- 8343736 TI - A decade of diabetes: keeping children out of hospital. AB - OBJECTIVES: To document the number of children aged less than 15 years who developed diabetes and were managed within one large health district, and to evaluate the outcome of those children managed without hospital admission at diagnosis. DESIGN: A retrospective study over 1979-88, when a paediatrician and a physician with special interests in childhood diabetes initiated joint clinics. Data collected from the district diabetes register and files of consultants and health visitors specialising in diabetes. SETTING: Referral of children to consultants in Leicestershire (total population 863,000). MAIN OUTCOME MEASURES: The proportion of children managed without hospital admission, comparison of readmission rates and glycated haemoglobin concentrations between children admitted and those not admitted. RESULTS: Over 10 years 236 children aged 10-14 years developed diabetes (annual incidence rate 12.8/100,000 child population (95% confidence interval 11.3 to 14.7)). In total 138 were not admitted to hospital but received supervised management based at home. Admitted children were younger or acidotic or their family doctors did not contact the diabetes team. Duration of admission declined from seven days in 1979-80 to three days in 1987 8. Ninety two were not admitted to hospital during the 10 years for any reason. Significantly fewer children who received management at home were readmitted for reasons related to diabetes than the group treated in hospital (30 (22%) v 40 (41%); p = 0.004). Concentrations of glycated haemoglobin were no different between the two groups. CONCLUSIONS: Children with newly diagnosed diabetes may be safely and effectively managed out of hospital. Domiciliary or community based management depends on the commitment of consultants specialising in diabetes working in close cooperation with general practitioners, specialist nurses in diabetes, and dietitians. PMID- 8343737 TI - Recruitment methods for screening programmes: trial of an improved method within a regional osteoporosis study. PMID- 8343738 TI - Fetal blood sampling in retreat. PMID- 8343739 TI - Why do adults sexually abuse children? PMID- 8343740 TI - Psychological consequences of screening for Down's syndrome. PMID- 8343741 TI - No escape: HIV transmission in jail. PMID- 8343742 TI - HIV outbreak investigated in Scottish jail. PMID- 8343744 TI - Case-control study of congenital anomalies in children of cancer patients. AB - OBJECTIVES: To determine whether the offspring of cancer survivors are at an increased risk of congenital anomalies and whether cancer therapy before conception is associated with such an increase. DESIGN: Case-control study using computerised record linkage. SETTING: Ontario, Canada. SUBJECTS: Parents of children born during April 1979 to December 1986 who had a congenital anomaly diagnosed within the first year of life (45,200 mothers and 41,158 fathers) and a matched sample of parents whose children did not have a congenital anomaly (45,200 mothers and 41,158 fathers). MAIN OUTCOME MEASURES: Cancer diagnosed in either parent before conception and radiotherapy to the pelvis or abdomen or chemotherapy with an alkylating agent. RESULTS: Among the mothers, 54 cases and 52 controls were identified as having had cancer diagnosed in Ontario (relative risk = 1.04, 95% confidence interval 0.7 to 1.5) and among the fathers, 61 cases and 65 controls were identified (0.9, 0.7 to 1.4). No significant associations were found between congenital anomalies in the offspring and any type of cancer treatment in either the mothers or the fathers. CONCLUSIONS: The risk of congenital anomalies among liveborn offspring whose parents have had cancer or been treated for cancer is not higher than that in the general population. PMID- 8343743 TI - Genetic susceptibility to non-insulin dependent diabetes mellitus and glucose intolerance are located in HLA region. AB - OBJECTIVES: To test the hypothesis that the genetic susceptibility to non-insulin dependent diabetes mellitus is the same as that to insulin dependent disease and to see whether glucose intolerance is associated with specific HLA haplotypes. DESIGN: Population based study of men in 1989 first tested for glucose tolerance in 1984. HLA haplotypes, including HLA-A, C, B, DR, and DQ, were defined serologically. HLA haplotype data from a population based Finnish study of childhood diabetes were used for predicting non-insulin dependent diabetes and impaired glucose tolerance. SETTING: Two communities in Finland. SUBJECTS: Representative cohort of Finnish men aged 70-89, comprising 98 men with non insulin dependent diabetes mellitus and a randomly selected group of 74 men, who served as controls, who were tested for glucose tolerance twice within five years. MAIN OUTCOME MEASURES: Non-insulin dependent diabetes, impaired glucose tolerance, blood glucose concentration. RESULTS: Diabetes associated HLA haplotypes were present in 94% (85/90) of diabetic subjects, 79% (27/34) of subjects with impaired glucose tolerance, and only 13% (3/23) of non-diabetic subjects. In this group of elderly men sensitivity of the diabetes associated HLA haplotypes for non-insulin dependent diabetes and impaired glucose tolerance was 90%, specificity 87%, and predictive power 97%. Mean fasting blood glucose concentration was only just significantly higher in men with diabetes associated haplotypes than in men with no such haplotypes, but there was a substantial difference in blood glucose values two hours after glucose loading (10.4 and 6.4 mmol/l in men with diabetes associated HLA haplotypes and men with no such haplotypes, respectively (p < 0.0001)). CONCLUSIONS: These findings support the hypothesis that specific HLA haplotypes exhibit a common genetic determinant for insulin dependent and non-insulin dependent diabetes. Furthermore, HLA is a major genetic determinant of glucose intolerance in elderly Finnish men. The belief that the HLA predisposition to diabetes is specific for insulin dependent diabetes mellitus is largely incorrect. PMID- 8343746 TI - Effect of spinal osteophytosis on bone mineral density measurements in vertebral osteoporosis. PMID- 8343745 TI - Factors affecting uptake of measles, mumps, and rubella immunisation. AB - OBJECTIVE: To study factors affecting uptake of measles, mumps, and rubella immunisation. DESIGN: Cohort study using data from computerised child health systems. SETTING: 10 health districts in North East Thames and North West Thames regions. SUBJECTS: 7841 children born in January to March 1990 and resident in the districts up till the end of October 1991. MAIN OUTCOME MEASURES: Overall uptake of measles, mumps, and rubella immunisation, variation of uptake among groups of children, and odds ratio of being vaccinated against measles, mumps, and rubella. RESULTS: The overall uptake rate of measles, mumps, and rubella immunisation for the study cohort in the 10 districts was 82%. Wide variation was identified among children with different demographic characteristics. Lower uptake was associated with absent or incomplete primary immunisation, including omission of pertussis vaccine. Other factors affecting uptake included the type of resident district, birth order, where registered for immunisation (general practitioner or clinic), and one parent family status. CONCLUSIONS: Many districts have difficulties in meeting the 90% target for measles, mumps, and rubella immunisation, mainly because of the characteristics of their local population. To increase overall coverage, the health service should target families with adverse factors, especially those whose children have missed previous immunisations. PMID- 8343747 TI - Late cardiac manifestation of infection with Borrelia burgdorferi (Lyme disease). PMID- 8343748 TI - Serum screening for Down's syndrome: some women's experiences. AB - OBJECTIVES: To describe the experiences of a small group of women who had positive results after serum screening for Down's syndrome. DESIGN: Semistructured telephone interviews and correspondence with women after a positive screening result (four women) negative amniocentesis results (eight), or termination of a pregnancy with a confirmed abnormality (eight). SUBJECTS: 20 women who contacted Support After Termination For Abnormality about their experiences of serum screening for Down's syndrome. MAIN OUTCOME MEASURES: Women's knowledge and understanding of the test; staff misconceptions; communication of results; how women coped with the diagnostic process; attitudes to the test and to termination of abnormal fetuses. RESULTS: All women were made anxious by their positive screening test, no matter how they were told. The women's experiences suggested that medical staff were unclear about the implications of screening tests and how to interpret risk. Even after receipt of negative amniocentesis results some women remained anxious. Staff did not always recognise women's concerns while awaiting amniocentesis results. CONCLUSIONS: The way in which serum screening is being implemented does not always meet the needs of women with positive results. Some of the problems were not specific to screening for Down's syndrome. When screening tests are introduced policies should be adopted to ensure appropriate support for participants. PMID- 8343749 TI - Personal computer software for handling references from CD-ROM and mainframe sources for scientific and medical reports. PMID- 8343750 TI - Methods of helping patients with behaviour change. PMID- 8343751 TI - ABC of one to seven. Health services for children: the community. PMID- 8343753 TI - Analgesia for children in intensive care. Consider the whole child. PMID- 8343752 TI - Analgesia for children in intensive care. Assessing pain is fraught with difficulties. PMID- 8343754 TI - Analgesia for children in intensive care. Paediatricians must take control of pain relief. PMID- 8343755 TI - Analgesia for children in intensive care. Study conclusions distorted by poor design. PMID- 8343756 TI - Analgesia for children in intensive care. Most units have acceptable written protocols. PMID- 8343757 TI - AIDS in Africa. PMID- 8343759 TI - Home treatment for acute psychiatric disorder. Innovative services merit investigation. PMID- 8343758 TI - Clozapine in the management of schizophrenia. All schizophrenic patients would benefit. PMID- 8343760 TI - Home treatment of acute psychiatric disorder. Inpatient treatment must remain an option. PMID- 8343761 TI - Management of patients in persistent vegetative state. Given proper rehabilitation a chance. PMID- 8343763 TI - Management of patients in persistent vegetative state. No one can define acceptable quality of life. PMID- 8343762 TI - Management of patients in persistent vegetative state. Economic arguments threaten all disabled people. PMID- 8343764 TI - Management of patients in persistent vegetative state. Moral arguments for ending life are flawed. PMID- 8343765 TI - Evidence for "clusters of anophthalmia" is thin. PMID- 8343766 TI - Management of patients in persistent vegetative state. Doctors should not be forced to practise euthanasia. PMID- 8343767 TI - Management of patients in persistent vegetative state. Reasons for withdrawing treatment should be explicit. PMID- 8343768 TI - Management of heparin induced thrombocytopenia. PMID- 8343769 TI - HIV and infection. Just say no. PMID- 8343770 TI - HIV and insurance. Catch 22. PMID- 8343771 TI - HIV and insurance. Insurers don't penalise if test result is negative. PMID- 8343772 TI - Doctors' HIV risk difficult to quantify. PMID- 8343773 TI - Assuring best practices in communication for children and youth with severe disabilities. PMID- 8343774 TI - Communication intervention for individuals with dual sensory and intellectual impairments. AB - For individuals with dual sensory and intellectual impairments, the lack of effective communication skills places severe limitations on their learning potential and sense of belonging. Educational intervention for this population has recognized the critical need to develop communication skills, yet the complexity of the individual's needs continues to plague progress. Unique needs and situations of individuals in this category, coupled with extremely limited numbers of trained and experienced professionals, challenge the field to develop creative means of addressing this vital issue. Documented case studies provide the field with examples of potential options to employ when addressing the communicative needs of individuals with dual sensory and intellectual impairments. However, these case studies provide partial communication systems that address partial communicative needs. Providing individuals having severe sensory, intellectual, and other disabilities with a true language that can meet all communication needs, both receptive and expressive, is still beyond our grasp. Future efforts with this focus will need to combine early intervention, creative technology, and principles of normalization in order to be successful. PMID- 8343775 TI - Enhancing curricula design. PMID- 8343776 TI - Functional communication training for challenging behaviors. PMID- 8343777 TI - Communication intervention for persons with severe and profound disabilities. AB - Traditionally, communication interventionists focused on teaching a beginning repertoire of communicative behavior, once learners with severe to profound disabilities had emitted intentional behavior. Increasingly, interventionists are recognizing that valuable opportunities may be lost if intervention does not begin at an earlier point. In part, intervention strategies at increasingly earlier points have resulted from a prevailing change from semantically-focused intervention logic to pragmatic, interaction-focused intervention logic. At the same time that intervention content has increasingly focused on pragmatics, there has been a wealth of information addressing the social functions served by repertoires of simple idiosyncratic (as well as socially unacceptable) behavior. The increasing availability of augmentative and alternative communicative options has provided an extensive array of motorically simple strategies to exert significant control and influence over one's environment. We have long since passed the need to demonstrate that persons with severe disabilities can be taught a repertoire of communicative functions. However, we have not been as successful in demonstrating that the communicative behavior taught is well maintained solely in the presence of natural maintaining contingencies. Nor have we adequately demonstrated that established repertoires are sufficiently generalized. Most recently, interventionists have begun to focus on more efficient strategies to use in the selection of the most critical teaching instances to teach a new communicative response. Additionally, interventionists are considering response efficiency as an important variable in determining the likelihood that a learner will choose to emit members of his or her communicative repertoire. There appears to be a consensus among those who currently serve individuals with severe disabilities that inclusion represents an attainable objective for students with even the most severe disabilities. Unfortunately, it is not clear that either special or regular educators are being adequately prepared to accomplish included placements. There remains a significant need to recognize those aspects of best practice which must be further explored in regular education settings. What once were considered best practice methods may not meet the test of social validity and be considered best practices in regular classrooms. The vast majority of intervention research has selected a fairly narrow communicative form or function to teach. Increasingly, information on maintenance and generalization is considered. However, often the periods sampled postacquisition are very modest. Among the plethora of available communication intervention curricula, there are virtually none that have taken a learner from a point of engaging in no intentional communicative behavior to the establishment of an effusive repertoire of communicative functions and corresponding vocabulary.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8343778 TI - Facilitating and measuring the team process within inclusive educational settings. PMID- 8343779 TI - Nonoperative management of secondary shoulder impingement syndrome. AB - Shoulder pain secondary to impingement of the rotator cuff tendons underneath the coracoacromial arch is a common problem seen in athletes who perform repetitive overhead activities. Shoulder impingement has been classified into primary and secondary types. Several factors contribute to impingement, including rotator cuff weakness, posterior capsule tightness, and subacromial crowding. Recently, it has been proposed that scapulothoracic muscle weakness could be a factor that contributes to impingement. Traditional rehabilitation protocols for shoulder impingement syndrome stress individualized rotator cuff strengthening. The authors propose that individualized scapulothoracic muscle strengthening should be a part of any protocol for nonoperative treatment of secondary shoulder impingement syndrome. PMID- 8343780 TI - Stretch-shortening drills for the upper extremities: theory and clinical application. AB - Enhanced athletic performance emphasizes the muscle's ability to exert maximal force output in a minimal amount of time. Exaggerated maximal muscular force develops due to athletic movements producing a repeated series of stretch shortening cycles. The stretch-shortening cycle occurs when elastic loading, through an eccentric muscular contraction, is followed by a burst of concentric muscular contraction. A form of exercise called plyometrics employs a quick, powerful movement involving a prestretch of the muscle, followed by a shortening, concentric muscular contraction, thus utilizing the stretch-shortening muscular cycle. The literature contains numerous references to plyometric training for the lower extremity, but there is a lack of information on the upper extremity plyometric program. Overhead activities, such as throwing, necessitate elastic loading to produce maximal, explosive, concentric muscular contractions. Plyometric exercise employs the concept of the stretch-shortening muscular cycle. The rehabilitation concept of specificity of training suggests plyometric exercise drills should be performed by the throwing athlete. This paper discusses the basic neurophysiological science and theoretical basis for plyometric exercise, and it describes an upper extremity stretch-shortening exercise program for the throwing athlete. PMID- 8343781 TI - Treatment of the inversion ankle sprain: comparison of different modes of compression and cryotherapy. AB - Relatively few studies have been performed to examine the effectiveness of different methods of treatment for the inversion ankle sprain. In this study, restoration of function following a grade II inversion sprain was compared among 34 subjects who received one of three methods of treatment, each of which incorporated an Air-Stirrup brace. The methods included uniform compression provided by elastic tape, focal compression provided by a U-shaped device, and focal compression with simultaneous cryotherapy. Although the results failed to demonstrate statistical significance at the .05 level (p = .055), the two groups that received focal compression attained each of nine levels of function in fewer days than the group that received uniform compression. The results of this study indicate that focal compression appears beneficial, but increased frequency and duration of cryotherapy does not appear to enhance the rate of recovery following an inversion ankle sprain. PMID- 8343782 TI - A comparison of temperature rise in human calf muscles following applications of underwater and topical gel ultrasound. AB - For ultrasound to be effective, a conducting medium must be placed between the soundhead and the skin. Little research has been performed to test whether or not these mediums actually work. The purpose of this study was to compare the effect of tap water immersion and ultrasound gel conducting mediums on tissue temperature rise in the human leg. A 23-gauge hypodermic needle microprobe was inserted 3 cm deep into the medial portion of the gastrocnemius muscle of 20 subjects. Each subject participated in two random order treatments using tap water immersion and topical gel conducting mediums. Each treatment consisted of continuous ultrasound delivered topically at 1.5 W/cm2 for 10 minutes. During both treatments, the soundhead was moved at a speed of 4 cm per second, and the temperature was recorded every 30 seconds. A significant difference was found between the two treatment methods [t(19) = 9.18, p < .001]. The topical gel increased tissue temperature 4.8 degrees C, whereas the underwater treatment increased tissue temperature only 2.1 degrees C. Therefore, at a tissue depth of 3 cm, ultrasound gel is a better conducting medium than water. Also, the authors discovered that it took nearly 8 minutes for the temperature to reach therapeutic levels during the gel technique. These findings should be of clinical significance to clinicians who regularly use ultrasound. PMID- 8343783 TI - The effects of unilateral velocity-specific concentric strength training. AB - There is conflicting evidence regarding the efficacy of various resistance training programs for increasing strength in trained and contralateral limbs. The purposes of this investigation were to examine the effects of unilateral velocity specific concentric isokinetic training of the extensor and flexor muscles of the elbow and knee on: 1) the carry-over effect in strength increases to velocities other than the training velocity in the trained limbs and 2) the cross-training effect at various velocities in the contralateral limbs. Twelve adult men (mean age +/- SD = 24 +/- 6 years) volunteered to train their nondominant extremities three times per week (six sets of 10 maximal repetitions) for 8 weeks at 120 degrees/sec using a Cybex II isokinetic dynamometer. The subjects were tested for increases in peak torque at 60, 120, 180, 240, and 300 degrees/sec. The training resulted in significant (p < 0.05) increases in peak torque on the trained side of the body for elbow extension and flexion as well as knee extension and flexion at all velocities tested. These findings indicated that the velocity-specific training resulted in increases in peak torque at velocities that were both greater and less than the training velocity. In addition, there was a cross training effect, with significant (p < 0.05) increases in peak torque on the contralateral side of the body for elbow extension (all velocities except 300 degrees/sec) as well as knee extension and flexion (all velocities). These results indicate that unilateral velocity-specific concentric isokinetic training is adequate stimulus for eliciting strength gains at a wide range of velocities in both the trained and contralateral limbs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343785 TI - Generalizability in focus. PMID- 8343784 TI - Relationship between active knee extension and active straight leg raise test measurements. AB - This study was conducted to determine the relationship between two alternative tests for indicating hamstring musculotendinous length, active knee extension (AKE) and active straight leg raise (ASLR). Before alternatives to a commonly practiced clinical test such as AKE can be recommended for application, their convergent validity should be established. Twenty-three healthy subjects (mean age = 29.4 years) were tested. A 35-mm camera was used to record the position of the right side of the pelvis and lower limb during the performance of the ASLR test on the right. The camera set-up was also used to record the position of the right knee and pelvis during the performance of AKE with the right hip flexed to 90 degrees. For ASLR, the angle of the straight leg to the horizontal was measured. For AKE, the angle of knee extension was measured. The intraclass correlation coefficients for the AKE (.861) and ASLR (.953) tests were good and high, respectively. There was a significant relationship (r = -.718; r2 = .515; p < .001) between AKE and ASLR. The significant correlation between the measurements obtained using these two tests suggests that both are providing an indication of the same basic phenomenon, presumably hamstring musculotendinous length. For this reason, the AKE test may be a useful alternative to the straight leg raise test for providing an indication of hamstring muscle length. PMID- 8343786 TI - Biomechanics of the elbow during baseball pitching. AB - By understanding pitching biomechanics, therapists can develop better preventive and rehabilitative programs for pitchers. The purpose of this study was to quantify and explain the joint motions, loads, and muscle activity that occur at the elbow during baseball pitching. Seven healthy, adult pitchers were examined with synchronized high-speed video digitization and surface electromyography. Elbow extension before ball release corresponded with a decrease in biceps activity and an increase in triceps activity. A varus torque of 120 Nm, acting to resist valgus stress, occurred near the time of maximum shoulder external rotation. Previous cadaveric research showed that the ulnar collateral ligament by itself cannot withstand a valgus load of this magnitude. Triceps, wrist flexorpronator, and anconeus activity during peak valgus stress suggests that these muscles may act as dynamic stabilizers to assist the ulnar collateral ligament in preventing valgus extension overload. PMID- 8343787 TI - The functional anatomy of the elbow complex. AB - The functional anatomy of the elbow joint complex is unique in orientation and configuration. Three bones, the ulna, radius, and humerus, articulate to form four articulations: the humeroulnar, humeroradial, superior radioulnar, and inferior radioulnar joints. This unique osseous structure provides the elbow excellent static stabilization, which is enhanced by the ulnar collateral ligament, the lateral collateral ligament, and the elbow joint capsule. Twenty three muscles are directly associated with the elbow joint and can be classified into four main groups: the elbow flexors and extensors and the flexor-pronator and extensor-supinator groups. These muscles provide dynamic stabilization to the elbow and enable the hand to perform skilled, precise motions. The purpose of this review article is to provide the clinician with an understanding of the unique anatomy at the elbow joint and to enhance the clinician's knowledge of the biomechanics, clinical examination, and rehabilitation of the elbow complex. PMID- 8343788 TI - Common elbow problems in the athlete. AB - Because of the popularity of sports participation, sports physical therapists must recognize in the athlete the many clinical conditions that occur about the elbow. The purpose of this paper is to present the most common elbow problems that an athlete may encounter and to provide information to facilitate recognition of elbow pathology. This information is essential before initiating treatment. An attempt is made to include sprains, strains, neuropathies, dislocations, fractures, contusions, vascular insults, and skin problems in the distal humerus, elbow, and proximal forearm of both the immature and mature athlete. Comprehension of the mechanism of injury aids clinical evaluation and rehabilitation and enhances early return to activity. PMID- 8343789 TI - Physical examination of the thrower's elbow. AB - The physical examination of the thrower's elbow presents the clinician with the clinical challenge of differentially diagnosing specific pathologies. The examination should include a thorough history and a well-organized physical examination, which relies on an extensive knowledge of the functional anatomy of the elbow. The components of an elbow examination include inspection/observation, palpation of bony and soft tissues, range of motion assessment, resisted muscle testing (both manual and mechanical), neurologic testing, and special tests. The special tests commonly performed on the thrower's elbow are the Tinel test, tennis elbow sign, ulnar collateral ligament stability testing, valgus extension overload test, and radiocapitella chondromalacia test. Other tests include radiographic examination, such as computerized tomograph arthrogram and magnetic resonance imaging testing. Information presented in this paper will provide the clinician with a systematic and thorough evaluation process for the thrower's elbow. PMID- 8343790 TI - Rehabilitation of the elbow in the throwing athlete. AB - Rehabilitation following an injury to the elbow joint complex is common in physical therapy practice. The unique anatomical considerations of the elbow joint provide a significant challenge to the therapist in rehabilitating elbow injuries. The purpose of this paper is to describe the rehabilitation process for various elbow pathologies and provide a rationale for their treatment. The rehabilitation process for the injured elbow presented in this paper will emphasize phases that are progressive, sequential, and based on clinical and scientific research. PMID- 8343792 TI - Sphygmomanometer vs. dynamometer. PMID- 8343791 TI - Ron Peyton Award Lecture. Quality, service, and innovation--the signature of a practice. PMID- 8343793 TI - Sympathetic effect of stretching: only neurogenic? PMID- 8343794 TI - Use of ultrasonography in the evaluation of the infertile man. AB - Transrectal ultrasonography (TRUS) is a modality that most urologists are familiar with in the interpretation of prostate anatomy and pathology. Understanding the anatomy and pathology of the genital ductal system will help in the diagnosis of disease entities related to male infertility. Familiarity with both scrotal and transrectal ultrasound is vital to the understanding and diagnosis of treatable causes of male infertility. PMID- 8343796 TI - Artificial intelligence in medicine and male infertility. AB - MAIN PROBLEM: fertility data is inadequately assessed by traditional statistical methods for a variety of reasons. First, the principal test of male fertility potential, the Semen Analysis (SA) is a composite of several dissimilar parameters, and the SA and other laboratory tests of fertility potential reflect physiological mechanisms that interact in complex ways. Second, patient data is often fragmented, obtained from multiple sources. Importantly, 2 patients are required for the final result. METHODS: Novel and powerful computational method, the neural network, was explored to analyze fertility data. An integrated series of programs was written in the C computer language to implement a back propagation algorithm. A model data analysis system was chosen, predicting the penetration of zona-free hamster ova by sperm (Sperm Penetration Assay (SPA)) and the distance travelled by the farthest swimming sperm (Penetrak Assay) from the SA, for these 2 assays are generally believed by the reproductive medical community to be independent of the SA. The classification accuracy of the neural network was compared to 2 standard statistical methods, linear discriminant function analysis (LDFA) and quadratic discriminant function analysis (QDFA). RESULTS: A neural network could be trained to correctly predict the Penetrak result in over 80% of assays it had not previously encountered, and another network could predict the SPA outcome in nearly 70%. The neural network was superior to LDFA and QDFA in predicting both assay outcomes (for Penetrak: LDFA = 64%, QDFA = 69%; for SPA: LDFA = 65%, QDFA = 45%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343795 TI - Preventable causes of male infertility. AB - The initial evaluation of the infertile man includes a diligent search for testicular factors, gonadotoxins, and coital factors so as to identify existing causes of impaired fertility and to prevent further dimunition in fertility. There are also prophylactic measures in the treatment of all men that can prevent future infertility, such as prompt correction of cryptorchidism, testicular torsion, genital infection, and adolescent varicocele and proper precautions to limit occupational, medical, and recreational gonadotoxins. PMID- 8343797 TI - The effect of age on male reproductive function. AB - When couples elect to defer child bearing, the effects of age on reproductive potential must be considered. The impact of advancing age on female reproductive potential has been well documented. Relatively less attention, however, has been directed toward the effect of age on male reproductive function. Although less pronounced than its effect on female fertility, advancing age does have an impact on male reproduction. Among men, increasing age is associated with a decrease in sexual function as well as changes in testicular histology and a decline in basic fertility parameters. Additionally, there is an identifiable association between advanced paternal age and subsequent birth defects. These issues should be borne in mind when men are counseled regarding the age at which they elect to establish families. PMID- 8343798 TI - Infection and pyospermia in male infertility. AB - Infections of the male genitourinary tract may contribute to infertility by adversely affecting sperm function, causing anatomical obstruction or initiating a leukocyte response. The majority of infertile males are asymptomatic, and the significance and the criteria for the diagnosis of a genital tract infection are controversial. The evaluation for a genital tract infection focuses on urine and semen cultures as well as on the accurate quantitation of seminal leukocytes. An elevated seminal leukocyte count, pyospermia, can be associated with male infertility and may reflect an infectious or inflammatory disorder. In addition, the role of specific genital tract infections such as chlamydiosis, gonorrhea, ureaplasma and trichomoniasis and their possible association with male infertility is addressed. PMID- 8343799 TI - Congenital bilateral absence of the vas deferens and cystic fibrosis. A genetic commonality. AB - CF and CBAVD are really just ends of a clinical spectrum. The type and nature of the mutations in the CF gene probably determine the phenotypic expression of the patient. Perhaps all patients homozygous for delta F508, for example, will have severe pulmonary and pancreatic disease as well as absent vasa, whereas those with other combinations, such as delta F508/D1270N, will be unaffected in terms of pulmonary and pancreatic function but will have absent vasa. Besides contributing to a better understanding of the nature of CBAVD, this linkage of CF and CBAVD most importantly mandates genetic screening and counseling for appropriate family members and even the patient's spouse. In addition, a broader understanding of CF is now at hand, as this brings a whole new cohort of patients under the CF umbrella. Many of these will have at least one, if not two, rare or novel CF gene mutations. Once all of these mutations have been detected and defined, our knowledge of the CF gene, its mutations, and their implications will be dramatically expanded. PMID- 8343801 TI - Laboratory testing in the evaluation of male infertility. A rational approach. AB - Laboratory testing is an integral component of the evaluation of the infertile man. This testing must be appropriate and specific for the individual couple. As there are many tests that evaluate various aspects of infertility, the urologist must understand what information the tests can offer as well as the limitations of each assay. The semen analysis remains the cornerstone of the evaluation but is not a functional assay. Other assays such as sperm-cervical mucus tests, hemizona assays, and the sperm-penetration assay are functional tests. Through the appropriate use of these and other tests, the urologist will be capable of better and more accurately counseling the infertile couple. PMID- 8343802 TI - Lelystad virus and the porcine epidemic abortion and respiratory syndrome. AB - Lelystad virus is the causal agent of a relatively new pig disease, variously known as mystery swine disease, porcine epidemic abortion and respiratory syndrome and porcine reproductive and respiratory syndrome. The virus is a small, enveloped RNA virus, that tentatively can be included in a new virus family, the Arteriviridae. The virus has infected pigs throughout the world and seems to persist in many pig populations and in individual pigs. Clinical signs of an infection with Lelystad virus are characterized by late term abortions and still birth in sows, and respiratory disease in piglets. PMID- 8343800 TI - Ejaculatory failure. AB - Although anejaculation is a relatively uncommon occurrence in the general population, over 12,000 new cases are reported annually. Anejaculation may result from spinal cord injury (SCI), retroperitoneal lymph node dissection (RPLND), diabetes mellitis, transverse myelitis, multiple sclerosis, or psychogenic disorders. At least 30% of men with this problem are or will be married and many will seek help to remedy their infertile state. The evolution of technique and instrumentation over the least 30 years has made electroejaculation an accessible and acceptable form of therapy. Recent successes in inducing ejaculation by means of rectal probe electrostimulation or vibratory stimulation combined with assisted reproductive techniques, such as zygote intrafallopian transfer (ZIFT), gamete intrafallopian transfer (GIFT), and in vitro fertilization (IVF), have provided these men a means of producing their own biologic offspring. PMID- 8343803 TI - [Viral epizootic in the marine seal calf (Phoca vitulina) in 1988. Epidemiological aspects]. AB - During the year 1988, an epizootic spread through European populations of harbour seals (Phoca vitulina). The first studies shed light on the importance of a new morbillivirus, close to canine distemper virus but different. However, other factors, like pollution by polychlorinated biphenyl (PCB) compounds may have played a part in the epizootic by increasing mortality. Up to then virology and pathology of wild populations of seals were not well known. This epizootic was an opportunity to learn about seal virus and their specificity, and to discover some biological and evolutionary implications of such a phenomenon. PMID- 8343804 TI - Morbillivirus infections in aquatic mammals. AB - Infections with morbilliviruses have caused heavy losses among different populations of aquatic mammals during the last 5 years. Two different morbilliviruses were isolated from disease outbreaks among seals in Europe and Siberia: phocid distemper virus-1 (PDV-1) and phocid distemper virus-2 (PDV-2) respectively. PDV-1 was characterized as a newly identified morbillivirus, most related to canine distemper virus (CDV), whereas PDV-2 most probably is a strain of CDV. Morbilliviruses were also isolated from porpoises--porpoise morbillivirus (PMV)--and dolphins--dolphin morbillivirus (DMV)--which had stranded on the coasts of Europe. PMV and DMV proved to be closely related to, but distinct from 2 ruminant morbilliviruses, rinderpest virus (RPV) and peste-des-petits-ruminants virus (PPRV). Serological surveys carried out among pinniped and cetacean species in the seas of Europe and North America indicated that infections with these newly discovered morbilliviruses or closely related viruses commonly occur among aquatic mammal species. PMID- 8343805 TI - Current status of the diagnosis and control of African horse sickness. AB - African horse sickness (AHS) is an infectious, non-contagious, highly fatal viral disease of Equidae, transmitted by arthropod vectors of the genus Culicoides, and endemic in Africa south and east of the Sahara. The disease is caused by a virus of the Reoviridae family, genus Orbivirus, and 9 serotypes have been recognized. Recent outbreaks of AHS in the Iberian peninsula and Northern Africa emphasize the need for accurate diagnosis and rapid implementation of control measures. In this paper, the epizootiological factors, clinical signs and necropsy findings of AHS are discussed, and an updated review of diagnostic laboratory methods together with a description of the main control measures is given. PMID- 8343807 TI - Special issue: New viral diseases of animals. PMID- 8343806 TI - [Bovine spongiform encephalopathy in Europe. Present and future]. AB - Occurrence since 1986 and extension as an extended common source epidemic in United Kingdom of a new neurological bovine condition: bovine spongiform encephalopathy (BSE) initiated numerous epidemiological research actions in this country in order to discover the origin of this new disease, predict its evolution and implement control measures. In the same time epidemiological surveillance systems have been set up in several European countries leading to the identification of sporadic BSE cases in Ireland, Switzerland and France. In spite of the numerous informations published, a number of topics are not precisely known: identity and origin of BSE agent, influence of contaminated bovine genetics over disease development in contaminated bovine, infection incidence in herds where disease has been identified. As BSE is a member of the group of transmissible spongiform encephalopathies, concerns about foodborne transmission from cattle to human and inoculation of medicinal products containing bovine material and used for therapy or prevention in human beings or animals, has been expressed. The demonstration of iatrogenic transmission between human beings of Creutzfeld-Jakob disease has considerably influenced the implementation of measures to prevent the hypothetical risk for man to be infected by medicinal products or medical devises containing material of bovine origin. PMID- 8343808 TI - [Anticoccidial vaccines. Review and perspectives]. AB - Coccidioses are a major problem for the poultry industry. Currently, the diseases are controlled by drug chemoprevention, but the development of chemoresistant strains has for several years incited investigators to search for a vaccine. Several methods were investigated: oocyst administration at low and controlled doses, administration of strains which had been attenuated by physical or biochemical means, immunization with extracted or recombinant antigens. For some years to come genetically selected precocious live strains of Eimeria which are now commercially available will be useful as vaccines; but in the future, genetically engineered antigens will provide new opportunities for a successful vaccination. PMID- 8343809 TI - Actinomyces pyogenes: susceptibility of 103 clinical animal isolates to 22 antimicrobial agents. AB - Actinomyces pyogenes induces suppurative diseases in ruminants and many other animal species. Most of the earlier antimicrobial susceptibility data has been obtained by disk diffusion techniques. Minimal inhibitory concentrations (MIC) of 22 antibiotics for 103 strains of A pyogenes of animal origin were determined by agar dilution test (Mueller-Hinton agar supplemented with 5% sheep blood). All the strains were susceptible to penicillin G, amoxicillin, methicillin, cephalothin, cefoperazone, pristinamycin, kanamycin, gentamicin, spectinomycin, chloramphenicol, vancomycin, novobiocin and rifampin. Fifty-nine percent were resistant to streptomycin, 67% to tetracycline, doxycycline and minocycline, 12% to erythromycin, spiramycin and lincomycin. Most of the strains resistant to macrolides and lincosamides exhibited a constitutive MLS(B)-like phenotype. In the cultural conditions used, it was not possible to determine accurate MIC of fucidic acid and pefloxacin. PMID- 8343810 TI - Liver biopsy in sheep. AB - Liver biopsies were performed in the same group of 16 sheep on 8 consecutive wk using an apparatus with a fibre optic continuous light source and a telescope. The sheep were placed in a sternal position on a special table constructed of metal pipes (3.8 cm diameter) and 4.5 cm spacing. Approximately 300 mg of fresh liver sample was removed from each sheep to be analyzed for copper or vitamin E. PMID- 8343811 TI - Comparative survival of first-stage larvae of small lungworms Muellerius capillaris and Neostrongylus linearis of goats in alfalfa and ryegrass plots. AB - Faeces from a goat infected with M capillaris and from another infected with N linearis were used to assess survival of first-stage larvae under natural conditions in northwest France in mid-autumn, at the high-risk period. The faeces were deposited on 3 plots covered respectively with ryegrass, short cut alfalfa and high alfalfa. The desiccation of faeces and survival of larvae were tested at 1, 7, 14 and 21-d intervals. Survival of M capillaris was much higher than that of N linearis in all plots. The lower desiccations were observed in the high alfalfa plot whereas the best survivals were found in the 2 other plots. Vegetation where faeces are deposited may thus play a part in the accumulation of parasitic risk on a pasture. PMID- 8343812 TI - Intra- vs intermuscular injections in swine. AB - In order to determine the exact localization (intra- vs intermuscular) in which a drug is injected when administered by a so-called intramuscular injection technique, a radiopaque test article (2 ml) was injected into the cervical musculature (2 sites), the loins and the gluteal mass in anaesthesized pigs. Immediately after this, the pigs were euthanized and deep-frozen. Then they were cut into slices, which were X-rayed to determine the exact localization of the test material. Semi-quantitative scores were given to each injection site according to the amount of test article found in or out of muscle mass and also to the absence or the presence of test article subcutaneously. The loins area obtained the highest score for intramuscular location, but in this site, injections were almost always followed by a flowing back of the test article to the subcutaneous' area. It was shown that an injection in the neck perpendicular to the skin surface just behind the base of the ear was the most appropriate site for intramuscular injection in pigs. PMID- 8343813 TI - Serum coloration as a criterion of the severity of experimental coccidiosis in the chicken. AB - Serum decoloration may be used as a criterion for the severity of coccidiosis. Direct measurement of serum coloration at 480 nm is easy to carry out and, with micromethods, it is not necessary to slaughter animals. With intestinal coccidia the sensitivity is high, and there is good correlation with the severity of infection and variability is small. With Eimeria tenella infection the criterion is less sensitive, but may be of value for some purposes. PMID- 8343814 TI - Suppressive effect of serum from pigs and dogs fed a diet deficient in vitamin E and selenium on lymphocyte proliferation. AB - The effect of sera collected from either pigs or dogs previously fed a vitamin E (vit E)- and selenium (Se)-deficient diet on in vitro lymphocyte blastogenesis response to mitogens was studied. Porcine sera were obtained from pigs used in 2 different trials. In I trial, 4-wk-old pigs received either a basal diet deficient in vit E and Se or the basal diet supplemented with Vit E, Se or Vit E and Se. Pigs were maintained on their respective diet for 25 d. Canine sera were collected from pups maintained on a deficient diet for 8 wk. Four dogs and 4 pigs maintained on a commercial diet were used as donors of peripheral blood lymphocytes (PBL). The addition of sera from pigs or dogs maintained on a vit E- and Se-deficient diet markedly suppressed both porcine and canine PBL response to mitogens. Porcine PBL blastogenesis was also suppressed when porcine or canine sera were added 8, 24 or 48 h after the beginning of the incubation period to culture containing 1% of fetal bovine serum (FBS). However, the suppressive effect caused by porcine sera was less severe than the one due to canine sera. Addition of 1% FBS in the cultures was sufficient to eliminate the suppression caused by the presence of sera from pigs fed a vit E- and Se-deficient diet. Other attempts to restore the lymphocyte response to mitogens by the addition of indomethacin, diethylcarbamazine or eicosatetraynoic acid, inhibitors of prostaglandin and/or leukotriene synthesis, were not successful. Because of the severe suppression caused by sera from animals maintained on a vit E- and Se deficient diet on the in vitro response of lymphocytes to mitogenic stimulations, it is very important to take precautions to avoid such deficiency. In vivo suppression of immunocompetent cells to antigenic stimulations may impair the capacity of the host to control infections. PMID- 8343815 TI - Using the social policy statement. PMID- 8343816 TI - The answer is in your hands. PMID- 8343817 TI - Casualisation crisis. PMID- 8343818 TI - Act condemned. PMID- 8343820 TI - Courageous nurses. PMID- 8343819 TI - Clients' rights: nurses' role. PMID- 8343821 TI - New Zealand Nurses' Organisation. Patients' code of rights and responsibilities. PMID- 8343822 TI - A bicultural journey. PMID- 8343823 TI - Nurses--get an attitude for the '90s. PMID- 8343824 TI - To know, you must pay. PMID- 8343825 TI - Promoting standards. PMID- 8343826 TI - [Intervertebral disc calcification in childhood]. AB - Author describes a case of calcification of the intervertebral disk in a child, observed simultaneously in two segments on the dorsal spine. During a long observation the signs of remission were observed. The case was thought worthy to be published because of the rare occurrence and the problematic differential diagnosis. PMID- 8343827 TI - [The effect of breach presentation on the development of the hips]. AB - Authors examined, using sonographic methods in 100 children with breech presentation, which of the intrauterine postures means a major danger in the development of hip dysplasia. It was found that acetabular alterations, requiring therapy or not, develop more frequently in groups in which the hips were in total flexion, the knees in semiflexion and the lower extremities in major external rotation. Based on their results they state that not the simple breech position is the greatest danger in the development of dysplasia and dislocation in babies born with breech presentation. PMID- 8343828 TI - [Injuries to the knee extensors. Rupture of the patellar tendon and the quadriceps]. AB - Authors discuss, based on the experiences of their 18 cases, the injuries of the knee extensors. 5 ruptures of the quadriceps and 9 of the lig. patellae propr. were observed in the 14 cases controlled. Based on their own experiences and the standpoints of the literature they suggest the operative therapy within 6 hours in the open injury and within 1-5 days following the accident in closed cases. The experiences, the operative technique, the viewponts of the aftercare and the end results are described. PMID- 8343829 TI - [A Cloward-type bone-harvesting technic in the management of pseudarthrosis of the navicular bone]. AB - Authors present an apparatus resembling the Cloward instrument, that can be however used more simply and safely for gaining a good quality cortico-spongious cylinder from the iliac wing. The functioning of the bone gaining instrument and the process of bone gaining is described. The apparatus was used in more than 100 cases for filling up with spongious bone chips the cavity arising after the cleaning of the pseudarthrosis of the navicular bone. Three different cases are presented to demonstrate the alternative applications of the apparatus. It is supported by literary data that the autologous bone gained from the iliac wing is the most suitable for transplantation. PMID- 8343830 TI - [Traumatic hip dislocation in childhood]. AB - Authors describe the diagnostic and therapeutic problems of the traumatic dislocation of the hip in children and report on the experiences of their 8 cases. It is stressed that the condition of the good result in the early diagnosis and reduction. For the recognition and treatment of the late complications a 1.5-2 years follow-up of the patients is thought to be important. PMID- 8343831 TI - [Use of a distally pedicled radial artery as an island flap for covering traumatic skin losses]. AB - Authors performed plastic operation using lower arm insulated flap with distal pedicle in 2 cases for covering traumatic skin defects on the dorsal side of the hand. Attention is called to the advantages of this method. Beside the shorter time of treatment in many cases a series of operations can be avoided by the primary covering with an insulated flap. PMID- 8343832 TI - [Use of preserved homograft for covering burn injuries]. AB - Authors describe the considerations supporting the use of cadaveric skin homografts. The surgical relations of the burns, the site and advantages of the application of the homografts in the treatment of the burned patients are summarized. PMID- 8343833 TI - [Corrective possibilities by subcapital metatarsal osteotomy in the management of hallux valgus and metatarsus primus valgus]. AB - The extent of correction achievable by inclined subcapital osteotomy of the metatarsus I. was studied in 100 cases of the deformation. The different angular values and dimensions were compared in the X-ray plates taken pre- and postoperatively and the clinical changes of the patients were evaluated on the basis of subjective complaints and objective symptoms. The angular limit values of the performability of osteotomy were determined. In deformations larger than the limit values wedge and half-wedge osteotomy, basisosteotomy, respectively, are the expedient methods. PMID- 8343835 TI - [DHS (Dynamic Hip Screw)-osteosynthesis in the management of femoral fractures in the hip region and the place of this method in the treatment of such injuries]. AB - In the last four years we performed 182 osteosynthesizes with Dynamic Hip Screw, besides other methods on the fractures of the hip region. Here we are presenting the evaluation of our results, which, regarding the international scene, fall into the medium category. The operations were performed within three days after the injuries in 61 per cent of our patients. Our results are good in 80 per cent of our patients. The incidence of method-specific complications is 15 per cent in our statistics/such as wound haematomas, local infections, cut out of the device of the femoral head, metal failures, the fracture of the femur at the site of the introduction of the device). The rate of complications is 30 per cent in case of Ender nailing. More than a 1 cm shortening in the fracture after weight bearing was observed in the 47 per cent of our DHS cases. Patients who are complaining of pain during weight bearing belong to this group. In accordance with other authors, we consider the DHS osteosynthesis, due to its high stability, the best technique in case of unstable pertochanteric fractures of elderly patients. We recommend the angular plate fixation to the pertrochanteric fractures in young patients, in whose case it requires a more accurate reposition and who are able to walk without weight bearing. We can achieve good results with Ender nails in case of stable pertrochanteric fractures of elderly patients. PMID- 8343834 TI - [Results of osteotomies in the management of valgus gonarthrosis]. AB - Authors report on the result of correction osteotomies in 31 cases of gonarthrosis, developed in consequence of valgus deformity. In 12 cases high tibial osteotomy, in 19 supracondylar femoral osteotomy were performed. The result was excellent in 15, good in 10 and poor in 6 patients. Decisive factors of the favourable result were partly the correction of the femorotibial valgus to around the physiological values, partly the horizontalization of the articular surface. In overcorrection the results deteriorate. The medial tilt of the tibial articular surface leads to the progression of the arthrosis. Supracondylar femoral osteotomy was found especially successful in the treatment of valgus gonarthrosis. High tibial osteotomy is suggested only in selective cases. PMID- 8343836 TI - [Surgical-technical problems of triple pelvic osteotomy. Early results of the polygonal method]. AB - Since the first description of the triple pelvic osteotomies papers reporting on the improvement of the operative technique were continuously published. This is explained by the more problematic details of the operation. Authors worked out to the technique of the polygonal triple pelvic osteotomy, published by Kotz, David and Uyka, a new exposure that makes more simple, quick and safe the performance of the operation. The essential feature is that the os ischii is reached after the osteotomy of the trochanter major from a lateral exposure and so the field of operation can be widely surveyed. At the same time transposition can also be performed. The experiences gained in 12 operations are reported, 8 of which were made according to their own method (follow-up: 8-22 months, in average 15 months). The patients were 14-33 years old and their complaints disappeared in every case. Authors suggest the operation for the correction of the dysplastic acetabulum in young adults and also in puberty after the fusion of the Y cartilage if no subluxation exists. Minor articular deformity and mild arthrosis are not considered as a contraindication. PMID- 8343837 TI - [A point system for the comparative evaluation of the treatment of acromioclavicular dislocations]. AB - Authors treated 165 patients for fresh acromioclavicular dislocation. In the period examined four different operative procedures were used for the transitory fixation of the joint. The results of treatment are assessed with a point system worked out by them. Their method makes the establishment of collective statistics, based on uniform points of view and extended to more institutions possible. By this an objective comparison on the effectiveness of the single conservative and operative methods of treatment will be practicable. PMID- 8343838 TI - [Transposition of the trapezius muscle in the management of deltoid muscle paralysis caused by injury to the axillary nerve]. AB - Authors report in connection with two cases, operated on with an operative procedure rather rare in the practice in this country. The deltoid paralysis, developed following the injury of the axillary nerve, was successfully treated with the transposition of the bony insertion of the trapezius muscle to the proximal part of the humerus. PMID- 8343839 TI - [Surgical treatment of inveterate Monteggia injury in childhood]. AB - Authors, based on the experience gained from the operative therapy of a 9 year old child with inveterated Monteggia injury, discuss the types, the diagnosis and the principles of treatment of this injury. They take the part of urgent treatment following early diagnosis as the results of the treatment of the non fresh cases are generally less favourable. PMID- 8343840 TI - [Aseptic femur head necrosis and therapeutic possibilities by using a bone graft with a vascular pedicle]. AB - The review of the occurrence, etiopathology, classification and diagnosis of the aseptic necrosis of the femoral head is followed by the description of the method of transplantation of the vascular pedicled bone graft. During 5 years implantation of 12 vascular pedicled bone grafts in 10 young patients with severe and of major extension necrosis of the femoral head was carried out. The early result was in every case the quick and significant decrease of pains and that the necrosis did not progress. In the early stage the severe consequence of the necrosis the collapse can be prevented with core decompression. In a later stage the vascular pedicled revascularization of the femoral head may retain in young patients, beside adequate hip movements, the gait and the working capacity. This, though it is not a final solution, will give chance by gaining time to perform prosthesis operations later. PMID- 8343841 TI - [Epidemiology of hand injuries based on surveys in Vas County]. AB - Authors have found in a 1 year survey in the county Vas 7580 hand injuries. The major proportion of young men and adolescents in the material was conspicuous. The types of accidents were investigated together with the place of the accident and types of the injury. The material shows that in contrary to the accidents of the work in the recent past the number of the accidents at home has increased- and so their prophylaxis became the main point. PMID- 8343842 TI - [Surgical management of acetabulum fractures]. AB - Author reports on the experiences with the operative treatment of 48 acetabular fractures in his Department during 19 years. He thinks that the operative treatment of the acetabular fractures may be successful only after the exact preoperative diagnosis and classification of the type of the fracture. After this the exposure may be chosen. During the operation one has to strive to the exact reconstruction of the articular surfaces and the performance of such stable osteosynthesis that will enable the early movements of the joint without weight bearing. If, because of the severity of the injury, the exact reconstruction of the acetabulum is not possible an effort must be made to create an anatomical situation that will give favourable conditions to late reconstruction operations (arthrodesis or endoprosthesis). Author describes after discussing the classification, diagnosis and treatment of the acetabular fractures his own results: in more than 3/4 of his cases excellent or good late results could be achieved. For this, with correct indication, the performance of the reconstruction operation is suggested. PMID- 8343843 TI - [Educational activities of the Hungarian National Institute of Traumatology]. AB - Author recalls the nearly four decades education activity of the National Institute of Traumatology and the Chair of Traumatology of the Postgraduate University of Medicine. The importance of the high standard therapeutical activity is stressed. Similarly the education based on scientific activity is also thought indispensable. He describes the technical conditions and the data of the more important courses. PMID- 8343844 TI - [Immediate full-range active movement after suturing of the flexor tendon. A new dynamic guiding splint]. AB - Immediate full range active movement after suture of the flexor tendon. New dynamic guiding splintAuthors emphasize based on literary data, the advantages of the active postoperative movements. A technique for suture and mobilization protocol are offered. They constructed a new dynamic guiding splint assisting the active movement and describe its preparation in details. Their own material, treated with the method suggested, is analysed. PMID- 8343845 TI - [Surgery of infected hand injuries in Bacs-Kiskun County]. AB - The therapy of the diseases of the infected hand belongs to the most difficult tasks of the hand surgery. In the county Bacs-Kiskun we have reached important results during the last two decades, described in this paper, together with the Hand Surgery Work Groups of the Accident Departments of Kecskemet (County Hospital), Baja and Kiskunhalas. PMID- 8343846 TI - [Use of a new fixation device--the intraosseal compression loop --in the management of articular (osteochondral) fractures of the hand]. AB - Author describes a new method, the intraosseal compression loop, unknown until now in this country for the treatment of intraarticular, osteochondral fractures. The advantages of the new method are analysed, attention is called however to the fact, that it can be used only in the therapy of certain types of fractures and it can be only one from the great variety of procedures for the treatment of osteochondrial fractures. It is demonstrated with a few examples that the method can be used to treat unstable diaphyseal fractures too. PMID- 8343847 TI - [Dorsal metacarpal vascular pedicled reverse flap]. AB - Author describes the anatomical basis and the possibilities of application of the dorsal metacarpal vascular pedicled reverse flap used first in this country. The vascular pedicled flap ins suitable to cover the skin and soft part defects over the dorsal surface of the ground phalanx of the long fingers and over the PIP joint. PMID- 8343848 TI - [Talus substitution using a vascular pedicled bone flap]. AB - Authors report on the substitution of in consequence of complete talus luxation, missing talus. It succeeded with the transplantation of a free vascular pedicled bone block, gained from the crista ilei to retain the length of the extremity and to secure the gait of the patient without aid, finally to make the return to the former active life possible. The use of the method in similar cases was found to be unknown after a review of the literature. This case is an example demonstrating the growing significance of microsurgery in the traumatology. PMID- 8343849 TI - [Examination of the reperfusion damage to a striated muscle: possible pathomechanism and prevention]. AB - We have examined in a series of experiments the pathomechanisms of the damage caused by the reperfusion following ischaemia of the striated muscle. The lipid peroxidation products (thiobarbitur acid-reactive materials [TBARS]) and the glutathion state were observed comparing the behaviour of the white and red fiber types. We have found significantly higher reduced and oxydated glutathion (GSH and GSSG) and TBARS values also in physiological circumstances in the red muscle fibers. At the end of a 4 hours ischaemia period no significant alteration was found in the above parameters though both the levels of GSH and GSSG were raised their ratio however did not change. We have measured expressed change with the elevation of the GSSG/GSH rate following a 1 hour reperfusion (108% +/- 22 in the white and 490% +/- 103 in the red muscle fibers) whereas the TBARS values still did not show significant elevation. In the second hour of the reperfusion the GSSG/GSH further elevated and beside this the expressed elevation of the TBARS could also be demonstrated (164% +/- 48 in the white and 152% +/- 28 in the red fibers. During the further reperfusion lasting altogether 12 hours we did not observe a significant decrease. The time sequence of these processes suggest that the lipiduperoxidation occurs only after the total exhaustion of the antioxidant reserves of the cell. The treatment with Methylprednisolon (MP), deferoxamine (DFO) and superoxid-dismutase+catalase (SOD+CAT) diminished in both types of fibers the raise of TBARS values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343850 TI - [The KT 1000 arhtrometer in the comparative study of stability of knee joints operated on for instability]. AB - In 1981 through 1989 authors performed 160 complex reconstruction operations for instability of the knee joint according to the basic principles of W. Muller, striving to restore all structures injured. 92 patients with 378 operations were controlled. The assessment of the results was based on the physical examination, the measurement of ligament laxity with the K 1000 arthrometer, the opinion of the patients, the level of their activity and Lysholm's functional point system was used. The stability of the knee could be restored in 73 per cent of the cases. The patients have thought the knees, found more stable with the arthrometer, really more stable. There was however no unambiguous relation between the knee stability and the level of activity of the patients. The most frequent complaint was pain, increased synovial fluid and the hindrance of squatting. The results were better if the patient had no previous operation in an other department and in those who did not need menisectomy, who had less operations, less body weight and better muscular force. PMID- 8343851 TI - Three monoclonal antibodies differentiate human from murine epidermis. AB - In order to establish a set of epidermal species markers, normal human skin, murine skin and human skin transplanted to nude mice were stained with monoclonal antibodies directed to cell membrane-bound carbohydrates, a basement membrane component and a structure in the cell nucleus. Three epidermal species markers were identified. Two markers stained exclusively human epidermis: LH7.2 detects type VII collagen and stained the basement membrane of human epidermis in unfixed frozen sections, while LP4N stained cell nuclei in human epidermis in methanol acetone-fixed frozen sections. The third marker, HH14, stained exclusively murine epidermis. HH14 defines the histo-blood group H carbohydrate antigen and stained spinous cell membranes of murine epidermis in both frozen and formalin-fixed sections. PMID- 8343852 TI - Vectorial delivery of newly-synthesized secretory proteins by human tracheal gland cells in culture. AB - The polarized secretion of newly-synthesized proteins of human tracheal submucosal gland cells was studied. Human tracheal gland cells were cultured on permeable filter supports allowing a separate biochemical analysis of apical and basal secretion. By transmission electron microscopy, confluent filter-grown cells were seen to form a continuous sheet of both multilayer and monolayer epithelial cells. Junctional complexes between adjacent cells were observed. On immunofluorescence microscopy, human tracheal gland cells in cultured exhibited characteristics of epithelial and secretory cells, including cytoplasmic staining for cytokeratin and for two secretory protein markers specific to the glandular serous type cell: lysozyme and antileucoprotease. [35S]methionine metabolic labelling experiments demonstrated that at least 90% of newly-synthesized secretory proteins were recovered in the apical medium. Moreover, lysozyme secretion was strongly polarized since 85% was released into the apical medium. Conversely, antileucoprotease secretion was more bidirectional since nearly 40% of released antileucoprotease was present in the basal medium. The fact that these two secretory proteins are released with differing relative polarity emphasizes that human tracheal gland cells exhibit at least two different exocytotic routing operations. PMID- 8343855 TI - Effect of the pericardium on systolic ventricular interdependence in the dog. AB - Systolic ventricular interdependence, whereby changes in left ventricular (LV) ejection alter right ventricular (RV) ejection, has been described. It is unclear, however, whether this interaction is influenced by pericardial volume constraint or by myocardial mechanical coupling. We hypothesized that if mechanical coupling were the primary factor determining systolic ventricular interdependence then it should be unaltered by the presence or absence of an intact pericardium, but affected by changes in LV end-systolic volume. We tested this hypothesis by observing the changes in RV stroke volume (SVrv) and peak systolic pressure (PSPrv) during a single LV isovolumic contraction under conditions of normal or increased (1.3 x normal) RV end-diastolic volume with and without an intact pericardium. In 10 anesthetized, open-chested dogs SVrv was derived from the integrated pulmonary arterial flow probe signal and RV ejection fraction (EFrv) was derived from the thermodilution plateau method and a rapidly responsive thermistor in the pulmonary artery. Right ventricular end-diastolic volume was considered to be the ratio of SVrv to EFrv. Left ventricular isovolumic contraction increased SVrv and PSPrv during all conditions (P < .01). However, PSPrv increased more when the pericardium was intact (P < .05). These data suggest that LV ejection can enhance SVrv and that this interaction is not appreciably altered by volume loading or the presence of an intact pericardium. Pericardial interactions may alter PSPrv but do not affect SVrv. PMID- 8343853 TI - Sodium bicarbonate versus Carbicarb in canine myocardial hypercarbic acidosis. AB - The objective of this study was to compare the in vivo effects of sodium bicarbonate (NaHCO3) and Carbicarb infusion on regional contractile performance and acid-base status in the setting of hypercarbic acidosis. Animals (N = 9) were anesthetized and paralyzed using sodium pentothal, halothane, and pancuronium bromide, and mechanically ventilated with an air-O2 mixture so that arterial PO2 was > or = 300 mm Hg. Following beta-adrenergic blockade, alveolar ventilation was gradually reduced over a 50-minute period to increase arterial PCO2 to 60 to 80 mm Hg. Each of the following solutions was then infused in consecutive order directly into the left anterior descending artery coronary artery for 15 minutes: (1) 8.4% NaHCO3 at 2 mL/min; (2) 5% sodium chloride at 2 mL/min, equivalent to NaHCO3 in osmolality; (3) 6.3% Carbicarb at 0.5 mL/min, equivalent to NaHCO3 in buffer capacity; and (4) 6.3% Carbicarb at 2 mL/min, equivalent to NaHCO3 in volume. Regional stroke work analog (ultrasonic dimension transducers), interstitial myocardial pH (Khuri electrode), coronary blood flow (doppler flow probe), and hemodynamic/metabolic variables (heart rate, blood pressure, arterial and coronary venous blood gases) were measured at 1, 5, 10, and 15 minutes during each infusion and 10 minutes after the infusion was discontinued, ie, at 25 minutes. Animals were allowed to recover for 45 minutes between interventions. Values at each time point were compared with baseline for statistical significance. Small reductions in interstitial myocardial pH (P < .05) and stroke work (P > .05) were observed within 1 minute of NaHCO3 administration. Both parameters increased significantly from baseline levels thereafter, ie, interstitial myocardial pH at 5 minutes and stroke work at 15 minutes. Infusion of Carbicarb invariably was associated with an increase (P < .05) in interstitial myocardial pH. Stroke work increased (P < .05) during low-dose Carbicarb administration, but infusion of the higher dose was accompanied by a biphasic response, ie, an increase (P < .05) from 0 to 5 minutes, followed by a gradual decrease that achieved statistical significance 10 minutes after termination of the infusion. End-diastolic length was inversely proportional to changes in stroke work, and coronary blood flow varied directly with changes in coronary venous Pco2. Myocardial O2 consumption decreased (P < .05) during Carbicarb infusion, but changes during NaHCO3 did not reach statistical significance. Our findings lend support to the hypothesis that intramyocardial pH determines myocardial function independent of CO2 production by buffer therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8343854 TI - Oxygen kinetics during liver transplantation: the relationship between delivery and consumption. AB - In anesthetized humans, oxygen consumption is independent of oxygen delivery above a critical threshold. Below this critical level, lactic acid is a marker of anaerobic metabolism and tissue oxygen debt, and heralds a supply dependency of oxygen consumption. The goal of this study was to determine whether a threshold value for oxygen delivery below which oxygen consumption becomes supply dependent can be identified in patients with normal, impaired, or absent liver function. Measurements were made in 34 surviving patients (group 1) and in 16 nonsurvivors with sepsis and postoperative liver graft failure (group 2). Hemodynamic measurements and blood samples were taken 10 minutes after introduction of anesthesia, 10 minutes after cross-clamping, and 10 minutes after reperfusion of the new liver. At these time points, we measured blood lactate, cardiac output, and arterial and mixed venous oxygen contents in order to calculate oxygen consumption and oxygen delivery. In both groups, cardiac output, oxygen delivery, and oxygen consumption decreased during the anhepatic phase and increased after unclamping of the inferior vena cava. Lactate increased in both groups during surgery, but was significantly higher in nonsurvivors (6.6 +/- 0.4 mmol/L) than in survivors (4.6 +/- 0.1 mmol/L) (P < .05). With similar changes for oxygen delivery and oxygen consumption during increased lactate levels we could not identify a clear supply dependency of oxygen consumption in survivors and nonsurvivors during liver transplantation. We conclude that the interpretation of blood lactate levels during circulatory shock can be biased due to a reduced lactate clearance in patients with impaired liver function, unrelated to the status of the relationship between oxygen delivery and consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343856 TI - Oxygen uptake-oxygen delivery alterations in the isolated liver after hydrogen peroxide challenge. AB - Acute, diffuse lung injury is frequently complicated by systemic organ injury and alterations in the relationship between oxygen uptake (VO2) and oxygen delivery (QO2). In this regard, systemic organ neutrophil accumulation and morphologic alterations consistent with systemic organ injury often occur in nonpulmonary organs in these settings. However, whether VO2-QO2 matching is also altered in these injured systemic organs remains unproven. Thus, the present study was designed to test the hypothesis that hydrogen peroxide (H2O2), a product of neutrophil oxidative metabolism, will cause systemic organ structural abnormalities and alter VO2-QO2 matching. To test this hypothesis, VO2-QO2 relationships, morphologic changes, and organ water content were evaluated in both uninjured, isolated perfused rabbit livers and in isolated perfused rabbit livers after injury with 5 mmol/L H2O2. Following H2O2 injury, peak VO2 fell from 1.36 +/- 0.35 mL/min/100 g to 0.79 +/- 0.16 mL/min/100 g (P < .05) and peak O2 extraction fell from 0.83 +/- 0.09 to 0.66 +/- 0.04 (P < .05). In addition, VO2 was lower for any given level of QO2 in the H2O2-injured livers compared with the control livers (P < .01). Finally, liver extravascular water content was increased in H2O2-injured livers compared with the control livers (0.79 +/- 0.02 v 0.71 +/- 0.05; P < .05). These observations indicate that H2O2, a product of neutrophil oxidative metabolism, is capable of producing both morphologic changes as well as gas exchange alterations in the isolated, perfused liver. PMID- 8343857 TI - Does alveolar recruitment occur with positive end-expiratory pressure in adult respiratory distress syndrome patients? AB - We studied the effects of positive end-expiratory pressure (PEEP) (2 to 14 cm H2O) on alveolar recruitment (Vrec), static respiratory compliance, and end expiratory lung volume (EELV) in nine sedated, paralyzed, mechanically ventilated adult respiratory distress syndrome patients. Positive end-expiratory pressure was applied in increasing and decreasing steps of 2 cm H2O. Flow, tidal volume, and airway pressure were measured. We used the rapid airway occlusion technique to determine static end-inspiratory elastic recoil pressure of the respiratory system (Pst, rs) and intrinsic PEEP (PEEPi). The changes in EELV were measured with respiratory inductive plethysmography. Alveolar recruitment was estimated as the difference in lung volume between PEEP and zero end-expiratory pressure (ZEEP) for the same end-inspiratory Pst, rs (20 cm H2O). We found that (1) Vrec with PEEP up to 14 cm H2O was in general rather small and was absent in two patients; (2) all patients exhibited PEEPi at ZEEP (5.6 +/- 1.0 cm H2O) and little change in EELV and Vrec was achieved until the external PEEP exceeded PEEPi; (3) if end-inspiratory Pst, rs is high at ZEEP, there is little or no alveolar recruitment with PEEP; and (4) Vrec and EELV were slightly higher during stepwise deflation than stepwise inflation with PEEP, except at ZEEP where EELV did not change after inflation-deflation runs with PEEP. PMID- 8343858 TI - Oxygen delivery-consumption relationship in adult respiratory distress syndrome patients: the effects of sepsis. AB - The oxygen consumption-delivery relationship (VO2/DO2) was studied in 15 sedated paralyzed patients with the adult respiratory distress syndrome (ARDS) due to multiple trauma and in whom sepsis was absent. Different levels (0 to 15 cm H2O) of positive end-expiratory pressure (PEEP) were applied. Oxygen delivery was calculated from cardiac index (thermodilution technique) and arterial oxygen content measurements. Oxygen consumption was calculated using Fick's equation. Regression lines were obtained for each patient. Oxygen supply dependency was defined as a significant (P < .05) relationship between changes in VO2 and DO2 with PEEP. Results were compared with those obtained in 18 ARDS patients in whom ARDS was due to sepsis. In nonseptic ARDS patients no significant relationship between changes in VO2 and DO2 with PEEP was found within the experimental range of DO2 on zero end-expiratory pressure (ZEEP) (347 to 845 mL/min/m2). None of these patients had multiple organ system failure (MOSF), and 73% survived. In ARDS patients in whom sepsis was present, supply dependency was present only when DO2 on ZEEP ranged between 330 and 640 mL/min/m2. All these patients developed MOSF and died. When DO2 on ZEEP ranged between 686 and 951 mL/min/m2 in septic ARDS patients, the supply dependency phenomenon was absent and only three patients developed MOSF and died (70% survivors). In almost all patients PEEP reduced DO2 and therefore worsened O2 balance by either increasing O2 extraction ratio and approaching the critical threshold for supply dependency or dismissing DO2 from the range of non-supply dependency. PMID- 8343860 TI - On the allocation of critical care resources. PMID- 8343859 TI - How gram-positive organisms cause sepsis. PMID- 8343861 TI - The influence of gender on conflicts of interest in the allocation of limited critical care resources: justice versus care. AB - After noting that the principle of autonomy has been inadequate for the resolution of many of the complex and difficult moral dilemmas involving conflicts of interest in the allocation of limited critical care resources, this paper analyzes the concepts of justice and care as alternative solutions to moral problems and applies them to the issue of repeat organ transplants to a single recipient. These concepts are found to be the basis of the notions of moral reasoning and moral orientation, respectively, which serve in moral development theory as two fundamentally different ways to approach moral problem solving. Following an elaboration of moral reasoning as found in Kohlberg's cognitive moral development theory, the influence of gender on moral reasoning is investigated. The empirical data show that women (mean Defining Issues Test score, 47.18) score significantly higher (P < or = .0001) than men (mean Defining Issues Test score, 41.77) in the use of moral reasoning based on the concept of justice for resolving moral dilemmas. Following an elaboration of moral orientation as found in Gilligan's moral theory of the ethics of care, the influence of gender on moral orientation is investigated. The empirical data show that women use the concept of care significantly more often (P < or = .0139) than their male colleagues in resolving moral dilemmas. From these data it is concluded that men are more likely than women to use justice in the resolution of moral dilemmas, such as the conflicts of interest in the allocation of limited critical care resources, but that if women do use, or are required by the social system to use, justice in the resolution of moral dilemmas, they do a better job of it than men. PMID- 8343862 TI - Stressing the critically ill patient: the cardiopulmonary and metabolic responses to an acute increase in oxygen consumption. AB - Critically ill patients frequently have compromised respiratory and hemodynamic function. Chest physical therapy has been previously shown to increase oxygen demand and therefore was used to examine how postoperative mechanically ventilated patients responded to an increased oxygen demand. We found that during chest physical therapy, oxygen consumption increased 52% +/- 37% (SD) over baseline values. There was a 35% +/- 32% increase in oxygen extraction and a 17% +/- 33% increase in oxygen delivery. Arterial and pulmonary artery pressures also increased. The cardiac output increase was due to increased heart rate with no change in stroke volume. The increases in minute ventilation and alveolar ventilation were not sufficient to eliminate the greater quantity of carbon dioxide produced, resulting in a small increase in PaCO2. There was no significant change in systemic vascular resistance. The increase in oxygen demand caused by chest physical therapy triggered an integrated physiological response that resulted in increased respiratory and cardiac performance. This in some ways, such as the lack of increase in systemic vascular resistance, resembles the response to exercise. PMID- 8343863 TI - Effect of anesthesia and surgery on plasma cytokine levels. AB - Cytokines released in response to stress may have a profound impact on circulatory stability. There is no information on the effect of general anesthesia alone on plasma cytokine levels and little information on cytokine release following surgery. Plasma cytokine levels and hemodynamic parameters were measured during anesthesia and abdominal surgery under sterile and nonpyrogenic conditions in seven pigs anesthetized with ketamine and pentobarbital. Tumor necrosis factor (TNF) was measured by bioassay. Bioassays of low and high sensitivity were used to measure interleukin 6 (IL-6). Measurements were made sequentially during: (1) 4 hours observation with anesthesia alone; (2) 2 hours following laparotomy and traumatic intestinal manipulation (IM) sufficient to produce shock; and (3) after an intravenous bolus of 1 microgram/kg endotoxin as a positive control. Arterial blood pressure decreased following IM from 91.5 +/- 5.8 to 48.6 +/- 3.2 mm Hg, (mean +/- SE, P < .05), with no further change following endotoxin. Heart rate was unchanged during the experiment, and central venous pressure decreased after endotoxin (P < .05). There were no increases in TNF or IL-6 (using a low sensitivity assay) with anesthesia alone or following IM with shock, but both increased after endotoxin administration (P < .05); using a high sensitivity assay, IL-6 did not change during anesthesia alone but did increase fivefold following IM with shock (P < .05) and 50-fold following endotoxin administration (P < .05). We conclude that in a porcine model under sterile and nonpyrogenic conditions, prolonged anesthesia does not increase plasma cytokine levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343864 TI - Allocation of critical care resources: entitlements, responsibilities, and benefits. AB - Determination of allocation of limited critical care resources appears to be an inevitable development. Criteria proposed to assign such limited resources among patients are not defined. It has been argued that allocation of critical care resources could be based on the principals of patient entitlements to health care, responsibilities of the physician to the critically ill patient, and beneficence. However, based on an analysis of the philosophical tenants of the Hippocratic Oath, there is little to support the concept of "sin" taxes or patient triage on the basis of judgment on the moral merit of the patient. PMID- 8343865 TI - Oxygen kinetics and the art of physiological monitoring. PMID- 8343866 TI - Positive end-expiratory pressure increases capillary pressure relative to wedge pressure in the closed and open chest. AB - The pulmonary arterial wedge pressure is used as a measure of left atrial pressure and frequently as an estimate of pulmonary capillary pressure. The arterial occlusion concept has recently been used to derive a pressure that is thought to be more representative of capillary pressure (Pcap) than wedge pressure (Pw). The object of this study was to measure the arterial occlusion Pcap at different positive end-expiratory pressure (PEEP) levels and to compare it with Pw. Anesthetized, paralyzed, supine, and mechanically ventilated dogs were instrumented with a Swan-Ganz balloon tip catheter (7F) for monitoring pulmonary arterial pressure (Pa), for measuring cardiac output (CO; thermodilution technique), and for performing the arterial occlusions. The postocclusion tracings were analyzed for Pcap in a conventional manner: exponential fitting of the data during the 2 seconds immediately postocclusion and back extrapolating to the instant of occlusion. Instant of occlusion was defined as the time when the Pa tracing began to deviate from the normal tracing. Pw was averaged from the data between 8 to 10 seconds after the occlusion. Increasing PEEP between 0 to 15 mm Hg caused a gradual decline in cardiac output in the closed and open chest conditions. Despite this decline, all three pressures (Pa, Pcap, and Pw) rose gradually in the closed chest. However, in the open chest, increasing PEEP from 0 to 4.7 mm Hg had no effect on the pressures, but between 4.7 and 13.4 mm Hg of PEEP, Pa and Pcap increased markedly with minimal change in Pw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343867 TI - Cardiopulmonary responses to continuous positive airway pressure in acute asthma. AB - The effects of nasal continuous positive airway pressure (CPAP) on expiratory flow, arterial blood gas tensions, cardiovascular status, and dyspnea were studied in 21 patients with acute asthma. Therapy consisted of the following CPAP sequence: 30 minutes at 5 cm H2O, 20 minutes at 0 cm H2O, 30 minutes at 7.5 cm H2O, and 20 minutes at 0 cm H2O. Six control patients were fitted with a CPAP mask but given no positive-pressure therapy. Significant reductions in respiratory rate occurred from a baseline of 22.0 +/- 1.0 to 19.8 +/- 3.8 breaths/min at CPAP 5 cm H2O and to 19.4 +/- 4.3 breaths/min at CPAP 7.5 cm H2O (P < .05). No significant change occurred in forced expiratory volume in 1 second (FEV1), heart rate, mean arterial blood pressure, or arterial blood gas tension with either level of CPAP. Dyspnea, as assessed by a breathlessness score, improved during CPAP therapy (P < .05). These levels of CPAP were tolerated without deleterious side effects. In comparison, the control group showed no change in heart rate, respiratory rate, or breathlessness score during the study period. These data show that application of CPAP in acute asthma reduces respiratory rate and dyspnea with no untoward effects on gas exchange, expiratory airflow, or hemodynamics. PMID- 8343868 TI - Systemic oxygen extraction can be improved during repeated episodes of cardiac tamponade. AB - We used a tamponade model to study the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during successive, reversible decreases in blood flow. In 7 pentobarbital-anesthetized and mechanically ventilated dogs, a catheter was introduced via a left thoracotomy into the pericardium to inject and to withdraw saline. Each experiment consisted of three steps. First, cardiac output was reduced by successive pericardial fluid injections until 4 to 6 data points were obtained in the dependent region of the VO2/DO2 plot (step 1). Second, cardiac output was restored by progressive withdrawal of pericardial fluid (step 2). Third, cardiac output was lowered again by reinjection of fluid into the pericardium until death (step 3). Expired gases were collected for determination of VO2. In each animal, critical DO2 (DO2crit), below which VO2 became DO2 dependent, was determined from a plot of VO2 versus DO2. When releasing tamponade, VO2 was restored to baseline. For the 3 steps, DO2crit were 10.5 +/- 2.2 mL/kg/min in step 1, 9.8 +/- 1.8 mL/kg/min in step 2, and 8.3 +/- 1.9 mL/kg/min in step 3 (P < .01 v step 1; P < .05 v step 2, respectively). There was no significant difference in VO2 at DO2crit for the three steps. Hence, critical oxygen extraction ratio (ERO2crit) increased from 60% +/- 12% in step 1 to 64% +/ 11% in step 2 (not significant) and to 73% +/- 12% in step 3 (P < .01). The VO2/DO2 dependency slope was also steeper in step 3 than in step 1 (0.77 +/- 0.31 v 0.54 +/- 0.20, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343869 TI - State of the art in upper-limb prosthetics. PMID- 8343870 TI - Fifty years of somatosensory research: from the Semmes-Weinstein monofilaments to the Weinstein Enhanced Sensory Test. AB - In this paper, the author's long history with somatosensation is overviewed with special emphasis on the creation of objective tests of sensibility. Objective testing is discussed using numerous examples from the author's experiences. The creation of the Semmes-Weinstein monofilaments is discussed. Tests employing the Semmes-Weinstein monofilaments, two-point discrimination, and point localization are discussed with reference to the fact that these tests reflect specific differences between the central and peripheral nervous systems. Towards that end, contrasts are made between the Semmes-Weinstein esthesiometer and both the two point discrimination and the point-localization tests. A new enhancement of the original Semmes-Weinstein monofilament test, the Weinstein Enhanced Sensory Test (WEST), is introduced. Advantages of the WEST are discussed. PMID- 8343871 TI - Localization of a constant-touch and moving-touch stimulus in the hand: a preliminary study. AB - There are limited normative data available defining a subject's ability to localize a constant-touch or moving-touch stimulus. The results that are obtainable to date have not been objectively measured so that they are reproducible. This study of a normal population suggests a standard to measure the error in a patient's capacity to localize both a constant-touch and a moving touch stimulus. The normative data demonstrate that in considering the ability to localize a constant-touch stimulus, there was less error of localization in the fingers than in the palm. The most sensitive finger was the index. In testing for localization of a moving-touch stimulus, seven types of responses were identified and classified. The procedure outlined in this study offers a means both to document the degree of sensory impairment in a more consistent manner and to objectively measure results of early-phase sensory re-education. PMID- 8343872 TI - Reliability of torque range of motion: a preliminary study. AB - The clinical reliability of torque range of motion (TROM) has not been tested. This preliminary review was performed to determine the intra- and interrater reliability of TROM. The proximal interphalangeal joints of the index and middle fingers of 14 normal subjects, 56 digits, were tested by applying extension forces of 200 g, 400 g, 600 g, and 800 g. Data were collected using both the hand held Haldex orthotic gauge with the dial goniometer (manual) and the cantilever beam force transducer and electrogoniometer (digital) as testing instruments. The testing order of digits, sides, and devices was randomized and tested separately by three different test teams. Results of the analysis of variance showed a significant difference of the means between raters at all force levels (p < 0.0001) and between instruments at 600-g and 800-g forces (p < 0.01). The Pearson product-moment correlation coefficient test, used to test the consistency, resulted in moderate consistency of measures of intrarater reliability between trials, and between instruments used (digital and manual). Intraclass correlation coefficients (ICCs) were calculated with results that were nearly identical to those of the Pearson. Intrarater reliability was in more consistent agreement at the 600-g and 800-g levels. There was significantly high agreement between the tests of tester B, compared with moderate correlations of the tests of testers A and C. PMID- 8343873 TI - Circumferential finger measurements utilizing a torque meter to increase reliability. AB - The purpose of this study was to compare the reliabilities of two methods of measuring finger circumference. Traditionally, finger circumference is determined clinically by the use of a tape measure. In this study, a tape-measure device for recording finger circumference utilizing a torque meter was compared with the traditional method to determine reliability differences. Ninety-two occupational therapists and occupational therapy students obtained circumferential measurements of the author's left index finger at the middle of the proximal phalanx utilizing the two methods. The readings obtained for each method were analyzed to determine the coefficient of variation and to compare their variances. The coefficient of variation for the traditional method was 2.92 and for the device utilizing the torque meter was 0.75. The F ratio was 15.63, which is significant at the 0.01 level. The results of this study indicate greater interrater reliability using a device that can accurately measure torque and allow the therapist to control the amount of tension applied when obtaining circumferential measurements using a tape measure. PMID- 8343874 TI - A protective orthoplast splint in the treatment of a patient with Colles' fracture by external fixation. AB - Discussion is provided of an Orthoplast splint that was used to aid in the successful treatment of a mentally deficient patient who had sustained a fracture in the distal forearm, which was managed by external fixation. This splint is advocated for the treatment of various types of uncooperative patients. Although this splint has not been tried in the treatment of children, it appears likewise applicable for a noncompliant youngster. PMID- 8343875 TI - Splinting the arthritic hand. PMID- 8343876 TI - Stress testing of the wrist using the dystrophile. PMID- 8343877 TI - Skeletal muscle architecture: implications for muscle function and surgical tendon transfer. AB - Skeletal muscles have mechanical properties that are well-described by the length tension relationship (for isometric contractions) and the force-velocity relationship (for isotonic contractions). These two intrinsic properties are scaled for a given muscle based on its architectural properties. Muscle active force-generating range is determined by muscle fiber length, while maximum muscle force is determined by physiologic cross-sectional area. These and other architectural properties should be matched between muscles when planning surgical tendon transfers in order to closely match donor and recipient muscles. Finally, the fiber length/moment arm ratio of a muscle-joint combination must be considered when describing strength because strength is a manifestation of both muscle and joint properties and not either alone. Unfortunately, detailed description of normal musculoskeletal design or optimal transfer strategy cannot be made until more basic science studies of the musculoskeletal system are conducted. PMID- 8343878 TI - A study of sensory recovery following carpal tunnel release. AB - The purpose of this study was to define the testing parameters that are most sensitive to sensory loss in carpal tunnel syndrome and then to track recovery of these sensations postoperatively. Two dozen patients underwent standard nerve decompression and were subsequently re-evaluated at six weeks, three months, and six months. The test battery included provocative maneuvers, light-touch threshold determined by manually applied monofilaments and skin indentation with the Automated Tactile Tester (ATT), manual two-point discrimination, manual high frequency vibration and ATT low-frequency vibration, and ATT warmth detection. The most sensitive indicators of sensory abnormality were the ATT low-frequency vibration and skin indentation tests. Responses to all but these two tests returned to normal within two months postoperatively. The ATT indentation and vibration tests showed continual improvement over the study period, returning to nearly normal values by six months. Recommendations concerning the use of automated methods for testing sensory function are made in light of these findings. PMID- 8343879 TI - The assessment and treatment of patients who have sensory loss following cortical lesions. AB - The assessment of tactile and proprioceptive sensory function in patients with severe sensory deficits resulting from cortical lesions is reviewed. The importance of using age-appropriate normative data to interpret the scores on these tests is discussed in the context of the frequency of ipsilateral disturbances in somesthetic sensation following unilateral cerebral lesions. Tactile and proprioceptive sensory deficits not only affect the processing of sensory information but also result in impairments in manual control. Fine-motor skills, such as those required for grasping and manipulating small objects, must therefore be evaluated in these patients. The treatment of patients with severe sensory deficits focuses on improving the perception of sensory information arising from receptors in the hand and on retraining motor function. The procedures used for sensory re-education and retraining are described. PMID- 8343880 TI - Endoscopic carpal tunnel release--current status. AB - Endoscopic carpal tunnel release is one of the most controversial topics in hand surgery today. Many surgeons have reservations in doing carpal tunnel release endoscopically because its merits and demerits have not been clearly defined. This article describes the various techniques now available to perform endoscopic carpal tunnel release. The anatomic basis for a single-portal technique using the Concept Carpal Tunnel Release Kit is described in detail. The results of 100 postoperative cases indicate that endoscopic carpal tunnel release was superior to the open technique in regard to postoperative morbidity and patient satisfaction in 92% of this patient group. PMID- 8343881 TI - Carpal tunnel neuropathy caused by injury: reconstruction of the transverse carpal ligament for the complex carpal tunnel syndromes. AB - A comprehensive surgical and therapy program for the management of carpal tunnel neuropathy caused by injury has been proposed. The program is based on the restoration of the gliding interface between the median nerve trunk, the flexor tendons of the fingers, and the inner gliding surface of the transverse carpal ligament. The development of these new gliding surfaces is achieved by a surgery program of circumferential mesoepineurolysis of the median nerve in the hand and wrist followed by an anatomic reconstruction of the transverse carpal ligament. This biologic process is completed by a postoperative program of immediate hand function and median nerve gliding. Three hundred consecutive surgical patients were studied to confirm that the elastic mobilization of the median nerve actually doubled after a comprehensive nerve mobilization, thus supporting the ligament closure and early nerve gliding. Patients who have been available for repeat electromyographic (EMG) study at four to six months show EMG improvement that supports the clinical improvement. Finally, mobilization of the median nerve as described in the study has shown nerve revascularization within 30 seconds after tourniquet release and biologic recovery signals in the postoperative nerve gliding period and has proven to be, from the nerve nutrition standpoint, a safe procedure. The reliability that has been achieved in median nerve recovery is due to the anatomic reconstruction of the entire transverse carpal ligament. This surgical technique has proven to be the step necessary to produce a symbiotic alignment of the median nerve and the flexor tendon gliding anatomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343883 TI - Evaluation and treatment of pain: aspects for nerve injury and rehabilitation. AB - Pain, or at least discomfort in the form of hypersensitivity, is always a sequela to nerve injury and nerve repair. A carefully planned pain evaluation and treatment program has been shown to result in a decrease in pain and improved function. For a hand therapist, the commitment to evaluation and management of pain is a personal as well as a professional dedication. Patients may greatly vary in their responses to injury, symptomatology, and treatment interventions. Although the hand therapist can successfully intercede with many patients, it is often advantageous to involve a clinical psychologist. Psychosocial and psychophysiologic data can be imperative in evaluating the possibilities of patient outcome with regard to pain, evaluation, and treatment. Psychophysiologic information is likely to increase the hand therapist's evaluation and treatment potency. A psychological assessment and/or intervention is appropriate at several points of treatment--for example, after an appropriate interval of healing time in which an injury should resolve itself, after a major invasive procedure such as surgery, or when a condition is chronic and all other avenues of treatment have been unsuccessful. PMID- 8343882 TI - A numerical grading scale for peripheral nerve function. AB - A numerical grading scale for median and ulnar function is outlined. This system, based upon the known pathophysiology of chronic nerve compression, creates a hierarchical scale of mutually exclusive categories for motor and sensory function. The scale is responsive to incorporating new technologies for sensorimotor evaluation if these should offer advantages in computer-assisted evaluation, validity, or reliability. The scale is assumed to be nonuniform, and nonparametric statistical analysis, such as use of the Wilcoxon rank-sum test, is appropriate. Where motor function may predominate the peripheral nerve function, such as the ulnar nerve, in contrast to the median nerve, the scale may be uniquely defined to reflect this attribute. Pilot study examples of application of the numerical scoring system are given, and specific areas to better define the scale through research are suggested. PMID- 8343884 TI - A dentist's experience with change of hand dominance. AB - Ten years ago as a young dentist, the author found himself completely unable to engage in his practice as a result of a serious nerve injury permanently affecting his dominant right hand and forearm. Some unique opportunities and chance encounters have enabled him to overcome the permanence of the injury and to advance into a dental specialty field considered very demanding bimanually. Chronicled below are the process by which this occurred and, in particular, the author's assessment of what led to the necessary change of hand dominance. Also described is an interesting process that was required by the admissions committee of the postgraduate specialty training program as part of their assessment of the author's ability to adequately perform clinical procedures prior to his admission into the program. Descriptions of certain office design changes as well as changes in instrumentarium and techniques and the inventions to support those changes are described. PMID- 8343885 TI - Cutaneous mechanoreceptors of the hand: experimental studies and their implications for clinical testing of tactile sensation. AB - This paper reviews selected research on the neurophysiology of cutaneous mechanoreceptors and their relationship to tactile sensations. Particular emphasis is placed on studies in which neurophysiological results are directly comparable to psychophysical results. These studies provide the strongest evidence for correlating mechanoreceptor function with specific tactile sensations. Furthermore, these studies have implications for how one should administer tactile stimuli in order to selectively stimulate particular groups of mechanoreceptors. PMID- 8343887 TI - Endocrine therapy for prostate cancer: recent developments and current status. PMID- 8343886 TI - The quest for better recovery from peripheral nerve injury: current status of nerve regeneration research. AB - The author reviews relevant nerve regeneration research in the past half-century to give the reader familiarity with the background of current research efforts. Recent research has been aided by newer knowledge of the biology of nerve regeneration. Early efforts to improve nerve regeneration centered on improvements in technical or surgical repairs, with only modest gains. Although current technical improvements with lasers or fibrin glue to repair nerves may show promise, the approach of deMedinaceli et al. combines several new ideas with some improvement experimentally. With the discovery of nerve growth factors and a host of newer nerve growth promoting factors, the biochemical arena has explored. Special tubes to repair nerves enable easy manipulation of the environment to study the effects of various factors on nerve regeneration. Silastic and bioresorbable tubes show the most promise to enhance nerve regeneration by tubulization. Because of the explosion of knowledge and high levels of activity of research, it is apparent that further improvements of nerve regeneration are on the horizon. PMID- 8343888 TI - Extracorporeal shock wave lithotripsy induces the release of prostaglandins which increase ureteric peristalsis. AB - The aim of this study was to identify the changes in secretion of prostaglandins into the urinary tract as a result of treatment by extracorporeal shock wave lithotripsy (ESWL) and to determine their effects on ureteric motility. Sixteen patients with renal or upper ureteric calculi were studied. A peripheral blood and urine sample was collected immediately before and after ESWL, with further samples taken 24 h later. The following variables were assessed by radioimmunoassay:prostaglandin E2 (PGE2), prostaglandin F1 alpha (PGF1 alpha), and thromboxane B2 (TXB2). An in vitro canine study was then designed to study the activity of TXB2, PGF1 alpha and PGE2 on an isolated intact canine ureter model. Significant elevations of TXB2 were found immediately after ESWL in both serum and urine, which fell almost to pre-treatment levels by 24 h. PGF1 alpha levels showed significant elevations at 24 h but no immediate increase as seen with TXB2. In contrast, PGE2 levels were unchanged in the urine but significantly decreased in the serum. In vitro studies showed that both TXB2 and PGF1 alpha repeatedly produced an increased frequency of ureteric contraction. ESWL results in the release of prostaglandins from the urinary tract which are shown to cause increased ureteric peristalsis. PMID- 8343889 TI - Choosing a powerful lithotriptor. AB - Clinicians have no yardstick to help them choose the most efficient lithotriptor. Their leading priority is a system allowing complete disintegration of the stone with the minimum number of shocks and a low re-treatment rate. One of the prerequisites of this system is a powerful shock wave generator. "Power" is as yet ill defined in lithotripsy. Therefore clinicians' choice depends upon other factors. Acoustic output measurements were recorded on 3 commercial lithotriptors representing the 3 main shock wave generating systems. These were the Dornier MPL 9000 (standard and X-155 electrodes), the Siemens (Lithostar, Lithostar Plus and System C) and the Wolf Piezolith 2300. The shock wave measurements were correlated to the capability of the lithotriptors to disintegrate standard stone models in vitro. Two factors were identified. The pulse intensity integral in the focus and the size of the focal zone proved to be the most important factors to assess and compare the efficacy or "power" of different lithotriptors. Together they can help clinicians to identify and choose the most efficient shock wave generating systems. PMID- 8343890 TI - Percutaneous nephrostomies. AB - A review was made of 127 percutaneous nephrostomies (PCN) in 106 patients with benign (74 patients) and malignant (32 patients) urinary tract obstruction. Data on underlying aetiology, complications, subsequent management and long-term management are presented. The study confirms that PCN is an effective and safe method of providing temporary or prolonged urinary diversion in obstruction. Its use in pelvic malignancy should be determined by the likelihood of obtaining worthwhile prolonged palliation in individual patients. PMID- 8343891 TI - Bladder Z-plasty for the repair of ureteric injuries. Experimental study in sheep. AB - There is general acceptance that the best substitute for a damaged distal ureter is an elongated bladder and that the bladder psoas hitch is the most reliable procedure. Nevertheless, it is not always sufficient to bridge a long ureteric gap. In order to obtain an equally safe but wider bladder elongation than the psoas hitch can provide, we have previously studied the effect of several Z shaped incisions on isolated pig bladders. The aim of the present study was to verify, in vivo, the efficacy and safety of the new technique. Five sheep underwent the psoas hitch procedure and 6 the Z-plasty procedure. The results showed that Z-plasty provides an equally safe but longer bladder elongation than the psoas hitch procedure. PMID- 8343893 TI - The bladder cooling reflex in man--characteristics and sensitivity to temperature. AB - The ice-water test is a simple supplementary urodynamic test that increases the precision of the diagnosis of overactive bladder subtypes. A similar bladder cooling reflex has recently been characterised in the cat and was found to originate from specific cold receptors in the bladder wall. In the present study, the threshold temperature of the human bladder cooling reflex was determined in patients with positive ice-water tests. Estimated threshold values were somewhat lower than those of the cat but still well above the temperatures required for cold stimulation of nociceptors. As in the cat, the strength of the cooling reflex varied inversely with the bladder temperature. These findings indicate that the human bladder cooling reflex is in principle organised in the same way as that of laboratory animals. The human bladder thus seems to be endowed with cold receptors with excitatory reflex connections to the detrusor. PMID- 8343892 TI - Retroperitoneal malignancy masquerading as ureteric colic. AB - This study reviews 6 patients who were referred with severe loin pain radiating to the groin and in whom a presumptive diagnosis of ureteric colic was made. Of these, 3 patients were found to have carcinoma of the pancreas and the remaining 3 had retroperitoneal lymph node metastases. Retroperitoneal malignancies rarely present with loin pain, but this diagnosis should be considered in patients with long-standing loin pain in whom an obvious diagnosis is not apparent. PMID- 8343894 TI - The ice-water test--a simple and valuable supplement to routine cystometry. AB - The results of cystometrograms and ice-water tests (IWTs) were retrospectively evaluated in 557 patients with overactive bladders, lower motor neuron lesions or pure stress incontinence. The IWT was considered positive when, following ice water instillation, the fluid was expelled from the bladder within 1 min. The test was considered false negative when no fluid escaped despite a sustained detrusor contraction of the same magnitude as the micturition contraction. Ninety seven percent of patients with complete and 91% of those with incomplete upper motor neuron lesions had a positive or a false negative IWT. About 75% of the patients with multiple sclerosis, Parkinson's disease or previous cerebrovascular accident had a positive IWT. All patients with lower motor neuron lesions or pure stress incontinence had a negative IWT. There was a significant correlation between a positive IWT and an abnormal sensation of bladder filling and inability to inhibit micturition voluntarily, as well as between a negative IWT and the occurrence of phasic detrusor contractions during cystometry. The study shows that the IWT is a sensitive test for differentiating upper from lower motor neuron lesions. It is also a useful parameter for functional subdivision of overactive bladders. In patients with voiding dysfunction in the absence of lower urinary tract inflammation, a positive test is an indicator of a silent or overt neurological disorder. PMID- 8343895 TI - Relief of pain following intravesical capsaicin in patients with hypersensitive disorders of the lower urinary tract. AB - We have extended our earlier observations on pain relief produced by intravesical instillation of capsaicin (10 microM in saline) in patients with hypersensitive disorders of the lower urinary tract. Patients in group A (n = 15) received intravesical capsaicin on days 0, 14 and 28: on each occasion the drug produced a warm or burning sensation, reduction in bladder capacity and a delayed, transient improvement or disappearance of symptoms. Patients in group B (n = 5) received intravesical capsaicin (10 microM at cystometry) 3 times on day 0. The initial sensation of warmth was experienced on each occasion, indicating that no significant desensitisation has been produced by the first instillation. Clinical improvement similar to that found in group A was observed. Three patients (group C) received warm saline (42 degrees C) at cystometry. This produced a pricking sensation, no change at cystometry and no subjective clinical improvement. Apart from the initial sensation of warmth, no patient in group A or B experienced side effects, either local or systemic. These findings confirm that intravesical instillation of capsaicin has a beneficial effect on patients with hypersensitive bladder disorders. Counter-irritation rather than desensitisation of primary afferents could be a possible mechanism of action. Further studies are needed to establish whether the intravesical administration of capsaicin or capsaicin-like agents represents a new form of treatment for relief of bladder pain. PMID- 8343897 TI - Extracorporeal shock wave lithotripsy for vesical lithiasis: initial experience. AB - The classical treatment for vesical lithiasis consists of surgery or endoscopic transurethral disintegration. These procedures require anaesthesia and hospitalisation. We report our experience with the Siemens Lithostar in 18 male patients with bladder stones. Complete fragmentation was achieved after a single session in 14 patients and 4 required 2 sessions. A 3-way Foley catheter with saline irrigation was used during treatment. Patients were treated in the prone position followed by immediate evacuation of stone fragments in 9 cases. Morbidity was minimal. Two patients developed impacted fragments and required stone retrieval. Extracorporeal shock wave lithotripsy (ESWL) for vesical lithiasis appears to be a simple, well tolerated and effective form of treatment. PMID- 8343896 TI - Extracorporeal shock wave lithotripsy for bladder stones. AB - Between December 1989 and July 1991, 29 patients with bladder stones were treated on the MPL 9000 extracorporeal shock wave lithotriptor using ultrasound for localisation. The mean stone dimensions were 22.65 x 15.17 mm (< 400 mm2 in 20 patients); 75% of patients required only 1 ESWL session but the largest stone (2025 mm2) required 3. Whilst larger stones tended to require more shock waves, linear regression analysis showed a poor fit and factors other than size (operator experience and stone hardness) may determine the number of shock waves required. Satisfactory fragmentation was obtained in all patients. All were treated under intravenous analgesia without anaesthesia. Three patients also had outflow obstruction and were treated by transurethral resection of the prostate (TURP) on the day after completing ESWL. ESWL prior to TURP reduces the morbidity and operating time associated with endoscopic therapy of bladder stones. Macroscopic fragments remaining after ESWL can be washed out at TURP. PMID- 8343899 TI - Is planned continuous irrigation indicated for haemorrhage following transurethral resection of the prostate? AB - A prospective audit was carried out of this unit's policy of non-irrigation following transurethral prostatectomy (TURP). Over an 11-month period 121 TURPs were performed. Only 29 patients required intervention to maintain bladder drainage post-operatively, 23 of these requiring bladder washout alone. In the remaining 6 patients catheter change and continuous irrigation were required. The weight of tissue resected was the only factor investigated which bore a significant relationship to the necessity for further intervention in bladder drainage post-operatively. Despite this, patients requiring continuous irrigation post-operatively could not be easily identified prior to or during surgery. PMID- 8343898 TI - Neobladder after cystectomy: an Indian experience. AB - A continent urinary reservoir was constructed from an ileocolonic segment and anastomosed to the urethra in 30 males after radical cystectomy for infiltrating bladder cancer. A small cuff of the prostate was retained for anastomosis with the reservoir and ureteric anastomosis was done from within the reservoir by the "pull through" method. Complete continence was achieved in 29 patients, all of whom had an adequate reservoir capacity exceeding 400 ml; they were able to empty the reservoirs satisfactorily as judged by the residual urine (< 50 ml). Urodynamic study revealed an intra-abdominal pressure < 30 cm of water at rest and at reservoir capacity of 500 ml. Early post-operative complications included urinary leaks in 3 patients, intestinal obstruction in 3 and a faecal fistula in 1. Deterioration of the upper tracts was noted in 5 cases. Twenty-seven patients are alive after a mean follow-up of 36 months. PMID- 8343900 TI - Continuous flow resectoscopes. Are the theory and design wrong? AB - The optical design of rod-lens telescopes has now reached a zenith. The only way of improving the resectoscope is to investigate the ergonomics and flow dynamics. We present a comparative analysis of the flow mechanics of continuous flow resectoscopes. The morphology, flow characteristics and irrigating potential (washout gradient) of several instruments were examined. It was found that when used with balanced continuous flow (inflow and outflow balanced), all of the endoscopes had poor visibility compared with unbalanced continuous flow (inflow > outflow). Possible changes in the design of the instruments are discussed. PMID- 8343901 TI - Audit and its impact in the management of early prostatic cancer. AB - An analysis was made of a prospective database of 614 men with newly diagnosed carcinoma of the prostate who presented between January 1978 and December 1990; 3 monthly updates were available on their clinical, haematological and biochemical parameters and 6-monthly updates on chest X-rays, bone scans and skeletal X-rays. It was found that 107 men (mean age 73.5 years) had early disease at presentation. Their management was based on regular surveillance and the treatment deferred until disease progression or development of symptoms. The audit of outcome measured various clinical events. Four patients (3.7%) developed local failure, 11 (10.3%) developed bone metastases, 3 (2.8%) died of cancer with a median survival of 6.3 years, and 34 (31.8%) died of intercurrent disease with a median survival of 2.6 years. The observed survival for 12 years of the whole group was similar to the expected survival for an age-matched population in Scotland. The standardised mortality ratio was 81 (95% confidence limits 57-112). PMID- 8343902 TI - Lipoprotein levels following treatment with cyproterone acetate or LHRH analogues. AB - Fasting serum lipoproteins were measured in patients with carcinoma of the prostate. Twelve patients were on no hormonal treatment (Group 1). Fifteen were on cyproterone acetate (Group 3), 17 were on the long-acting LHRH analogue Zoladex (Group 4) and 11 on a combination of cyproterone acetate and Zoladex (group 5). In addition, 27 patients with benign urological disease were taken as controls (Group 2). In both groups in which cyproterone acetate was part of the treatment the total high density lipoprotein cholesterol levels were significantly lower than in the other groups. Patients on cyproterone acetate alone had significantly higher levels of very low density lipoprotein (VLDL) triglyceride levels than those not on cyproterone acetate. These results confirm changes in serum lipoprotein levels in patients taking cyproterone acetate and these changes may have potential adverse effects if the treatment is prolonged. PMID- 8343903 TI - Effects of neurogenic bladder dysfunction in utero seen in neonates with myelodysplasia. AB - Twenty neonates with myelodysplasia were prospectively evaluated during the first month of life with urodynamic studies, contrast voiding cystourethrograms (VCUG) and renal ultrasound scans. Ten of 20 infants had abnormal VCUGs--6 with vesicoureteric reflux (VUR) and 4 with bladder trabeculation alone. Only 2/20 neonates had abnormal ultrasounds--both with hydroureteronephrosis secondary to VUR. Elevated leak point pressure (LPP) and/or detrusor sphincter dyssynergia (DSD) were present in 10/20 infants--6 with elevated LPP and DSD, 3 with elevated LPP alone and 1 with DSD alone. Eight of 10 neonates with DSD or elevated LPP had abnormal VCUGs--4 with VUR and 4 with bladder trabeculation alone. Conversely, 8/10 neonates without DSD or elevated LPP had normal VCUGs. Contrast VCUG performed shortly after birth, therefore, is essential for the discovery of bladder trabeculation and reflux. There is a strong correlation between an abnormal VCUG and the presence of DSD and elevated LPP, suggesting that neurogenic bladder dysfunction in utero can lead to these structural abnormalities. PMID- 8343904 TI - Evaluation and treatment of incontinence after bladder neck reconstruction in exstrophy and epispadias. AB - Twenty-five children with exstrophy/epispadias who had had at least one bladder neck operation (but no augmentation) for incontinence underwent cystometrography (CMG) and urethral pressure profile (UPP) studies. The purpose of this study was to examine all components of lower urinary tract function and to determine how the properties of the bladder and the properties of the bladder neck/urethra interacted to achieve continence or to result in incontinence in the individual child. Examination of detrusor function during filling revealed involuntary contractions in 12 children and an end-fill pressure > 10 cm H2O in 8. Of the 21 children in whom voiding could be evaluated only 6 could initiate a detrusor contraction. In the 18 incontinent children leak pressure could be measured and was > or = 15 cm H2O in 12. Five of the 7 continent children also demonstrated at least one abnormality in lower tract function. The maximum pressure of the UPP did not agree with the leak pressure and may not be a valid measure of the closing pressure of the bladder neck/urethra in this patient population. Detailed urodynamic investigation is necessary in these children to guide the next step of management and to evaluate objectively each form of treatment. PMID- 8343905 TI - Sequential self-castration and amputation of penis. PMID- 8343906 TI - Pseudoregression of pulmonary metastasis after nephrectomy for renal carcinoma. PMID- 8343907 TI - Vesico-acetabular fistula after total hip replacement. PMID- 8343908 TI - Apparent Buschke-Loewenstein tumour of the penis. PMID- 8343909 TI - Primary seminal vesicle choriocarcinoma. PMID- 8343910 TI - Re: J-wire facilitates retrograde manipulation of ureteric calculi prior to extracorporeal shock wave lithotripsy. PMID- 8343911 TI - Bladder cancer in patients undergoing haemodialysis. PMID- 8343912 TI - Re: Surgery for hypospadias fistula. PMID- 8343913 TI - "The ICO cometh". PMID- 8343914 TI - Management of dislocated lens fragments following phacoemulsification surgery. AB - Twelve patients with retained nuclear lens fragments following phacoemulsification surgery were referred for management. Ocular findings included corneal edema in 4 (33%), elevated intraocular pressure in 6 (50%), vitreous inflammation in 10 (83%) and retinal detachment in 1 (8%). At initial examination 10 of the patients had a visual acuity of 20/200 or less. Two patients were managed conservatively with medical treatment and regained 20/20 and 20/25 vision. Ten patients required pars plana vitrectomy; in six a posterior chamber lens was sutured into the ciliary sulcus after vitrectomy was completed. Postoperatively, 5 of the 10 surgically treated patients regained 20/40 or better vision. Preexisting age-related macular degeneration and chronic cystoid macular edema were the causes of a poor visual result. PMID- 8343915 TI - Effect of a topical anesthetic cream (EMLA) in reducing pain caused by infiltration of local anesthetic in eyelid surgery. AB - EMLA (eutectic mixture of local anesthetics) cream is a topical formulation of a mixture of lidocaine and prilocaine. It has been used to achieve local analgesia after application under an occlusive dressing. We carried out a double-blind randomized controlled clinical trial to assess the effect of 5% EMLA (25 mg/mL of lidocaine and of prilocaine) in reducing the pain caused by infiltration of local anesthetic in eyelid surgery. Pain was assessed by means of a modified visual analogue scale ranging from 0 (no pain) to 10 (excruciating pain) in 25 consecutive patients (average age 65 years) undergoing bilateral eyelid surgery. Clinical significance was defined as a difference in pain scores of 3 or more between EMLA and placebo. The mean pain scores for EMLA and placebo were 3.1 and 4.0 respectively, a nonsignificant difference. The EMLA preparation was found not to be clinically effective in reducing pain caused by infiltration of local anesthetic in eyelid surgery. PMID- 8343916 TI - The role of colour flow Doppler ultrasonography in the investigation of disease in the eye and orbit. AB - Colour flow Doppler ultrasonography is a relatively new technique in which colour encoded representations of flowing blood are imposed over a conventional grey scale ultrasound image. This allows interrogation of a relatively large volume of tissue to determine the presence and direction of blood flow. The waveform tracings are then evaluated by means of conventional Doppler imaging. We demonstrate examples of normal vascular structures in the orbit and describe the application of this technique in the investigation of vascular disease, such as carotid-cavernous fistula and ischemic disease. The technique can also be used to evaluate ocular membranes and masses. Colour flow Doppler imaging promises to be an important advance in ophthalmic ultrasonography. PMID- 8343917 TI - Posterior scleritis: ultrasound and clinical findings. PMID- 8343918 TI - Orbital abscess due to acute dacryocystitis. PMID- 8343919 TI - Monosporium apiospermum endophthalmitis in a patient without risk factors for infection. PMID- 8343920 TI - Congenital trichomegaly, pigmentary degeneration of the retina and growth retardation (Oliver-McFarlane syndrome): 28-year follow-up of the first reported case. PMID- 8343922 TI - The CNS influence on patient autonomy. PMID- 8343921 TI - Legislative and regulatory update: health care reform and managed competition: implications for CNSs. PMID- 8343923 TI - A model for the development of the CNS role in adolescent health promotion self care. AB - A meaningful definition of the CNS has been difficult to express because of the versatility of the role, yet a clear understanding of the role responsibilities is essential to ensure successful implementation of the CNS position within a select client population. Adolescence is a period in the life-span that represents such a population. Adolescents undergo certain cognitive changes that render them vulnerable to health-damaging behaviors often initiated during this stage of development. Health promotion self-care strategies by the CNS are important in helping the young person incorporate positive health practices in daily activities. A conceptual model, based on Orem's general theory of nursing, has been developed through literature review and refined through practical application. It is presented as a framework by which health promotion needs of the adolescent may be predicted, recognized, and satisfied through components of the CNS role, the basic concepts of Orem's model, and characteristics of adolescent cognitive development. PMID- 8343924 TI - Facilitating acceptance of a patient's decision to stop treatment. AB - Quality of life is a very personal issue. When illness reaches a point where life is believed to be intolerable, people may choose to stop treatment. This paper presents an intervention model for psychiatric liaison nurses to utilize in order to facilitate acceptance of such a decision. The model contains two parts: assessment and intervention. The assessment process can be broken down into five parts to include the assessment of self, patient, family, nursing, and medical staff. Intervention strategies to expedite acceptance include opening communication, resolving conflict, being a go-between, and advocating for the patient. PMID- 8343925 TI - Survey research. PMID- 8343926 TI - A survey of 636 staff nurses: perceptions and factors influencing the CNS role. AB - The specific aim of this investigation was to document the perceptions of the CNS role and the factors influencing the role. The Clifford Clinical Specialist Functions Inventory was used to survey staff nurses at two affiliated medical centers. A 38% response rate was obtained. A total of 636 surveys were returned. Analysis of the data indicated: the CNS was perceived as valuable; physical presence of the CNS on the nursing unit enhanced role enactment; and a list of CNS role expectations could be developed based on perceptions of staff nurses. The results indicated that perceptions of the CNS role did not vary among staff nurses at the two medical centers. PMID- 8343927 TI - Management does not equal leadership. PMID- 8343928 TI - Families need help too: group treatment for families of nursing home residents. AB - Despite long-standing interest in the family as the focal point of nursing care, there are few published reports of clinical interventions with families after they institutionalize an elderly relative. Family members experience loss, guilt, and grief, and report that these emotions continue throughout the time that their older member is in the nursing home. This paper presents the rationale for using a supportive, educational group approach with families of nursing home residents and describes a family group intervention, detailing the role of the geriatric mental health nurse specialist, group goals, and the focus of each session. Evaluations by families and staff are presented, and recommendations for practice are made. PMID- 8343930 TI - The role of the CNS in developing systems of health care delivery. PMID- 8343929 TI - Incorporating midmanagement skills in an oncology CNS program. AB - Today's health care system requires that CNSs be prepared to manage care within complex organizations as well as deliver expert care to individuals and their families. The integration of midmanagement preparation with clinical knowledge and skills is critical. In this paper, we (1) review the literature pertaining to the role of oncology CNS and management preparation, (2) describe the program at the University of Pennsylvania School of Nursing, and (3) identify the management content that was added to strengthen the theoretical and clinical components of the program and to prepare our graduates in assuming leadership positions. PMID- 8343931 TI - Enhancing case management through computerized patient files. AB - The need for developing an organizational system for managing a large patient specialty population prompted the use of a computerized data entry and retrieval system. The use of a computerized system has facilitated patient case management, chart organization, and development of accessible data for research. Patient data fields (topic headings) are used for: (1) storing specific categories of patient data, (2) compiling lists for management and research, and (3) referring physician and patient/family contact information. Various lists can be compiled from the field data base in order to develop research and patient management lists. Patient management lists are used to track a patient's progress, provide quality assurance of care, and contribute researchable data. Also, patient information can be transferred automatically from the computerized daily management system into a computerized form letter. Individualized patient letters may be generated. Laboratory and test information from the last clinic or hospital visit can be mailed to families along with a handwritten personalized interpretation of their results by the CNS or physician. PMID- 8343933 TI - The business of consultation. PMID- 8343932 TI - Novice CNS and role acquisition. AB - A master's-prepared nurse in an introductory role as a CNS will find the experience both challenging and rewarding. The CNS's first year is a time of self exploration, stimulation, ambivalence, and growth, both professionally and personally. These nurses are often experienced clinicians who strive to be in positions in which they can affect a large group of patients and colleagues with both their knowledge and expertise. Stress occurs because the experienced nurse who has felt competent, confident, and comfortable in his or her previous role as a direct caregiver is now in the role of novice CNS who must learn the expectations and responsibilities of a new role, and develop a broad set of new skills. Utilizing the Dreyfus model, as applied to the nursing profession by Benner, this article will explore the transition of the nurse from experienced staff nurse to novice CNS. Enhancing and restraining factors that influence role realization, as well as effectiveness in supporting staff, to achieve optimal outcomes for patients will be identified. PMID- 8343934 TI - The business of being an expert witness and legal consultant. AB - Nurses serve as expert witnesses and provide legal and other consultation for which they receive compensation. Although numerous articles describe the process of serving as an expert witness and providing consultation, the business aspects of such consultation is seldom addressed. Most nurses have little experience in managing the business and financial aspects of such consultation. To be a successful consultant, clinical expertise and business acumen are necessary. Suggestions are given for creating a system of record keeping, keeping track of expenses, billing for services, reporting expenses and income for tax purposes, and marketing services. PMID- 8343935 TI - A strategy for staff development: self-care and self-esteem as necessary partners. PMID- 8343936 TI - In theory and practice. PMID- 8343937 TI - [The improvement of the Doppler echocardiographic method for the estimation of pulmonary systolic pressure]. AB - The formulas currently utilized for noninvasive evaluation of right ventricular systolic pressure (RVSP) include right ventricular-right atrial pressure gradient (RV-RAG) and right atrial pressure (RAP). The former is expressed by trans tricuspid systolic flow velocity, the latter is generally assumed. We recently observed that ultrasound estimation of RAP through inferior vena cava collapsibility index (CI) may help in the choice of the more appropriate formula for the evaluation of RVSP. However, these traditional methods (method A:RV-RAG + 10; method B:RV-RAG x 1.1 + 14) have limitations, particularly when RAP is low. The present study was undertaken to improve noninvasive estimation of RVSP through new formulas based on CI prediction of RAP. One hundred and four patients, in whom tricuspid regurgitation was adequately documented with CW Doppler, were included in this study. They were classified into 3 groups: Group 1 with CI > 45%, Group 2 with CI < or = 35%, Group 3 with CI 35-45%. RVSP was evaluated by 3 different methods: A, B, and C. Method C was based on CI, assigning 6, 16, or 9 mmHg to RAP (respectively, the mean values in the 3 groups of our previous study). Results indicate that method C improves noninvasive estimation of RVSP in Group 1 and Group 2, with respect to other methods, with reduction of the SEE and of the mean difference of the t-test between hemodynamic and echographic values. In Group 3, Doppler estimation by method A and C, and catheter measurements are comparable, whereas method B significantly overestimates the actual value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343938 TI - [Coronary angiography in a defined population: a pilot study of the residents of Padua]. AB - In recent years there has been a steady increase in number of coronary angiography procedures and coronary angioplasty. Since these interventions are relatively expensive, we tried to evaluate the appropriateness of coronary angiography indications. A retrospective pilot study was undertaken on all residents in Padua who had had a coronary angiography performed in 1988. In order to take into account patients who, although resident in Padua, had a coronary angiography performed outside Padua or even abroad, all Italian Hemodynamic Centers and the Office for Foreign Cures Authorization of ULSS 21 were contacted. Follow-up was stopped on April, 1991. Patients were first checked if living by consulting the Register's Office of the Community of Padua; they were then interviewed by letter on state of health. One hundred twenty-four patients underwent 138 coronary angiography. Utilization rate is 5.6 per 10,000 people (CI 4.6-6.6). This figure is lower than the present USA utilization rate, and is similar to the rate of late 70's. From patient records, 3 out 8 groups emerged as predominant indication for coronary angiography: unstable angina (37%), valvular heart disease (20%) and recent myocardial infarction (20%). According the ACC/AHA guidelines, indication was considered "appropriate" in 69%, "inappropriate" in 7%, "doubtful" in 20% and impossible to evaluate in 5% of cases. Although this classification may have been built up with incomplete information, it is note worthy that the percentage of inappropriate indication is comparable to that of other reports. A further observation is that not in every case the treatment assigned at the time of diagnostic angiography was really carried out on the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343939 TI - [Myocardial revascularization in patients with compromised left ventricular function]. AB - From March 1988 to March 1992, 69 patients with coronary artery disease (CAD) and left ventricular dysfunction (LVD) were referred to our Institute for surgical decision making. Sixty-nine (8.2%) had LVD. In 39/69 patients we performed the identification of viable myocardium with the use of [18F] FDG/PET in fasting conditions. We divided patients with LVD into 3 groups: Group A (30 patients) operated on without preoperative [18F] FDG/PET, Group B (32 patients) with FDG uptake in akinetic segments, and Group C (7 patients) with no FDG uptake; there was no significant difference among the 3 groups in age, sex, CAD, risk factors and ejection fraction EF (Group A: 29.1 +/- 6.6%, range 16-40; Group B: 32.9 +/- 6.5%, range 20-40; Group C: 26.5 +/- 6.8%, range 18-37). All patients underwent [99mTc] MIBI/SPET to assess perfusion at rest and [99mTc] MIBI first pass radionuclide angiography to assess the EF. The study of perfusion and EF was repeated 6 months postoperatively in Group A and B. Myocardial protection was achieved according to the Buckberg protocol. Operative results in Group A and B were respectively: in-hospital deaths 2 (6.6%) versus 0 (NS), perioperative myocardial infarction 1 (3.3%) versus 1 (3.1%) (NS), IABP 10 (33.3%) versus 4 (12.5%) (p = 0.048). Postoperative EF improved both in Group A (35.1 +/- 7.1%, range 20-50; p = 0.01) and in Group B (44.2 +/- 7.7%, range 26-62; p < 0.001). In Group C 6/7 patients were scheduled for heart transplantation according to standard criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343940 TI - [The lipid profile after heart transplantation in relation to the preoperative cholesterolemia and to the main pathology]. AB - Serum cholesterol plays a role only in the etiology of ischemic cardiomyopathy and increases in patients after heart transplantation. Aim of the present investigation was to verify whether lipid profile change is related to pre intervention type of cardiomyopathy and serum cholesterol level. Lipid profile was monthly monitored for at least 6 months in 21 consecutive patients after heart transplantation (19 males and 2 females, mean age 47 +/- 10 years). Serum cholesterol and triglycerides increased in all patients 2 months after surgery and thereafter it persisted significantly elevated. The increase was statistically significant only in patients with dilated cardiomyopathy and with normal cholesterolemia before surgery. In conclusion, lipid profile after heart transplantation should be especially monitored in patients with dilated cardiomyopathy and in those with normal serum cholesterol before heart transplantation. PMID- 8343941 TI - [Mechano-electric feedback and ventricular arrhythmias in heart failure. The possible role of permanent cardiac stimulation in preventing ventricular tachycardia]. AB - Left ventricular dysfunction has been identified as the strongest independent predictor of sudden death in patients with ventricular tachyarrhythmias. It has been suggested that some of these arrhythmias might be due to myocardial stretch which may alter cellular electrophysiological properties. In heart failure (HF) the abnormal mechanics of contraction may directly initiate an arrhythmia by mechano-electric feedback (MEF), defined as changes in mechanical state that precede and alter transmembrane potential. So far, the significance of MEF and its role in clinical arrhythmogenesis have received minimal attention. We report data of 3 patients, aged from 60 to 64 years (mean age 62 +/- 2), affected by HF from 28.3 +/- 3.5 months and ventricular arrhythmias recorded by Holter: premature contractions, couplets, nonsustained ventricular tachycardia (VT). Sinus rhythm was present in 2 patients, atrial fibrillation in the last one. Many VT episodes started after an abrupt spontaneous increase in ventricular cycle length or following an ectopic beat. A permanent VVI pacemaker (MEDTRONIC Legend) was implanted in each patient and programmed at different rate from 50 to 80 b/min. During the upper rates, 70 and 80 b/min, VT episodes decreased from 292 +/ 181 to 161 +/- 95 and 97 +/- 63 (p < 0.05), respectively. In fact, the permanent pacemaker could prevent the lengthening of ventricular cycle and the myocardial fibers stretch due to the increase in ventricular volume. In conclusion, in patients with HF and ventricular arrhythmias a pacemaker may be useful in preventing VT episodes and, probably, sudden death. PMID- 8343942 TI - [What is cytochrome P-450? Enzyme forms of cytochrome P-450--extent of knowledge]. AB - The submitted review summarizes contemporary knowledge of the enzyme P 450, the importance of which in human metabolic processes has been beyond doubt for a long time. The existence of various forms of the enzyme (there is a number of enzymatic forms of this haemoprotein which does not differ only as regards the structure of the alipoprotein but also as regards some physical and chemical properties) was proved in many prokaryotic and eukaryotic organisms. It played a special role in herbivores. New forms were detected which can be induced e. g. by polycyclic hydrocarbons, barbiturates, steroids, ethanol (1), hypolipidaemic substances and some antibiotics. Also other regulating factors are known. The clinical use of P 450 is complicated so far by the great genetically conditioned multiplicity of its forms in man. However, a number of very promising and important applications are foreseen. PMID- 8343943 TI - [Changes in blood pressure, proteinuria and renal hemodynamics in type I diabetes with manifestations of diabetic nephropathy after 2 months of captopril therapy]. AB - In 15 type I diabetics with manifest diabetic nephropathy the authors investigated the antihypertensive and antiproteinuric effect of captopril and in seven patients of this group also its effect on renal haemodynamics. Captopril treatment or its combination with hitherto used antihypertensive treatment was associated after two months with a significant drop of the systolic and diastolic blood pressure from 150/95 (120/70-195/110) to 130/90 (110/65-180/115) mmHg, (p < 0.005 < 0.05). The median aortic pressure declined from 118.5 (92-140.8) to 106.5 (84-1334.8) mm Hg (p < 0.005). Nine of 11 patients (82%) could be changed to reduced antihypertensive therapy. The antiproteinuric effect was manifested in 11 patients (73%). Quantitative proteinuria dropped from 2.7 (0.83-8.65) to 1.85 (0.38-8.84) g/24 h., (p < 0.05) without a significant change of serum creatinine: 109 (70-342) vs. 135 (90-288) mumol/l, p = n.s.). The change of proteinuria, as compared with the baseline value, was -41 (-77 - +88)%, (p < 0.05) and did not correlate with the change of the median aortic pressure (correlation coefficient = -0.165, p = n.s.). In the group of seven patients the change of the median aortic pressure was -15% (-26.1 - +6.6), (p < 0.05). No statistically significant change of glomerular filtration was observed: 0.96 (0.32-1.38) vs. 0.96 (0.19 1.71) ml/s, p = n.s.); effective renal plasma flow: 6.32 (2.24-7.74) vs. 7.22 (1.68-10.55) ml/s, (p = n.s.); filtration fraction: 0.136 (0.123-0.220) vs. 0.130 (0.110-0.236), change 0.0 (-43.0 - +31.0)% (p = n.s.) and renal vascular resistance: 15429 (12907-54148) vs. 13243 (7099-77832)%, (p. = n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8343944 TI - [T-lymphocyte subpopulations in bronchoalveolar lavage in pulmonary sarcoidosis and other interstitial pulmonary diseases]. AB - In the bronchoalveolar lavage of 17 patients with pulmonary sarcoidosis and in the lavage of 18 patients with other diseases of the pulmonary interstitium the authors assessed by means of monoclonal antibodies, T-lymphocyte subpopulations. In the lavage from sarcoidosis helper-inducer lymphocytes (CD4+) dominated markedly, while in other interstitial pulmonary diseases a predominance of suppressor-cytotoxic lymphocytes (CD8+) was found. The different ratio of CD4+ and CD8+ lymphocytes was manifested particularly markedly when for evaluation the CD4/CD8 ratio was used: in sarcoidosis it was 7.2 +/- 3.5, while in other interstitial lung diseases only 0.9 +/- 0.6. The presented results indicate possible practical use of assessment of lymphocyte subpopulations in bronchoalveolar lavage for the differential diagnosis of interstitial lung diseases. PMID- 8343945 TI - [Immunologic study in HIV-positive patients. Hypergammaglobulinemia in HIV infection]. AB - In all groups of patients--HIV, ARC, AIDS carriers--elevated serum concentration of IgG, IgA, IgM were found. In the group of HIV carriers a significant increase of the serum concentration of IgG at the 5% level was observed and of IgM at the 1% level. In patients with ARC a significant increase of IgG and IgA was found at the 5% level and of IgM at the 1% level. In patients with AIDS significantly raised IgG values at the 5% level were recorded, and of IgA and IgM at the 1% level. In IgA a permanent increase of values occurs in AIDS carriers. In the AIDS stage 86% of the patients have values higher than mean +/- SD of controls. In all three stages of HIV infection a rise of concentrations of circulating immunocomplexes was observed (p < 0.01). The highest levels were recorded in patients with AIDS. In none of the patients the presence of antinuclear antibodies was detected. The authors discuss also possible causes of hypergammaglobulinaemia in HIV infection. PMID- 8343946 TI - [Therapy of ulcer disease using gastrinal-sucralfate produced in Czechoslovakia]. AB - The authors present their experience with the use of the Czechoslovak preparation Gastrinal-Sucralphate in the treatment of 40 subjects with gastroduodenal ulceration. Moreover, they compared two forms of the drug--tablets and granulate. The healing effect of the drug is very high, in tablets 77.0%, in granulate as much as 89.5%. As far as tolerance is concerned, it was obviously better after the granulate, subjective side-effects were very rare. The drug does not affect any basic biochemical parameters which were monitored during administration of the drug. PMID- 8343947 TI - [Ethics committees in the Czech Republic]. AB - The authors submit a report on the establishment and activities of new advisory organs which developed in hospitals and at medical faculties and bear the name of ethical commissions. Their task is to approve grants, advisory activities as well as organizing public discussions of ethical problems. The basis of the report are data obtained by means of questionnaires completed by 62 respondents. At present there are 20 ethical commissions in the Czech Republic, 19 local ones and one central one. PMID- 8343948 TI - Extracellular signals and reversible protein phosphorylation: what to Mek of it all. PMID- 8343949 TI - The torso receptor protein-tyrosine kinase signaling pathway: an endless story. PMID- 8343950 TI - Exercising self-restraint: discouraging illicit acts of S and M in eukaryotes. PMID- 8343951 TI - JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. AB - Erythropoietin (EPO) regulates the proliferation and differentiation of erythroid cells through interaction with its receptor (EPOR). Although EPOR is a member of the cytokine receptor superfamily and lacks a kinase domain, EPO induces tyrosine phosphorylation, which is correlated with gene transcription and mitogenesis. Here we demonstrate that EPO induces tyrosine phosphorylation of JAK2 kinase and activates its in vitro autophosphorylation. Using EPOR mutants, phosphorylation and activation of kinase activity correlate with the induction of mitogenesis. Furthermore, JAK2 physically associates with a membrane-proximal region of the EPOR cytoplasmic domain that is required for biological activity. The results support the hypothesis that JAK2 is the kinase that couples EPO binding to tyrosine phosphorylation and mitogenesis. PMID- 8343952 TI - Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. AB - Growth hormone receptor (GHR) forms a complex with a tyrosine kinase, suggesting involvement of a ligand-activated tyrosine kinase in intracellular signaling by growth hormone (GH). Here we identify JAK2, a nonreceptor tyrosine kinase, as a GHR-associated tyrosine kinase. Immunological approaches were used to establish GH-dependent complex formation between JAK2 and GHR, activation of JAK2 tyrosine kinase activity, and tyrosyl phosphorylation of both JAK2 and GHR. The JAK2-GHR and JAK2-erythropoietin receptor interactions described here and in the accompanying paper provide a molecular basis for involvement of tyrosyl phosphorylation in physiological responses to these ligands and suggest a shared signaling mechanism among members of the cytokine/hematopoietin receptor family. PMID- 8343953 TI - Transcytosis of the polymeric Ig receptor requires phosphorylation of serine 664 in the absence but not the presence of dimeric IgA. AB - MDCK cells expressing the polymeric immunoglobulin (poly-Ig) receptor, cocultured with IgA-producing hybridoma cells, transported dimeric IgA (dIgA) from the basolateral into the lumenal compartment, where it was recovered as secretory component-dIgA complexes. The tail of the receptor was phosphorylated on serines 664 and 726. Each serine was mutated to alanine. Appearance of A726 receptor at the basolateral surface was reduced approximately 5-fold. This was accompanied by a approximately 5-fold reduction in dIgA transcytosis. Basolateral delivery of receptor was not affected by mutation A664, and in the absence of dIgA, the receptor accumulated in recycling basolateral endosomes. In coculture, however, dIgA transcytosis by A664 receptor was normal. Thus, entry of receptor into the transcytotic pathway requires Ser-664 phosphorylation only in the absence of dIgA. PMID- 8343954 TI - The chondroitin sulfate form of invariant chain can enhance stimulation of T cell responses through interaction with CD44. AB - Invariant chain (Ii) is a nonpolymorphic glycoprotein that associates with major histocompatibility complex class II molecules and has been shown to mediate several functions in class II-restricted antigen presentation. A small proportion of Ii is modified by the addition of chondroitin sulfate (Ii-CS), and this form of Ii is associated with class II on the surface of antigen-presenting cells. In this report we show that expression of Ii-CS dramatically enhanced the ability of class II-positive EL4 transfectants to stimulate class II-dependent allogeneic and mitogenic T cell responses. Antibody blocking studies and the ability of CD44 to bind directly to Ii-CS suggest that Ii-CS can function as an accessory molecule during T cell responses through interactions with CD44. PMID- 8343955 TI - Biosynthesis of succinoglycan, a symbiotically important exopolysaccharide of Rhizobium meliloti. AB - The exo genes of Rhizobium meliloti are needed for the synthesis of an acidic exopolysaccharide, succinoglycan. We have assigned biosynthetic roles to the products of the exo genes by characterizing succinoglycan biosynthetic intermediates from exo mutant strains. We propose a model of succinoglycan biosynthesis in which the products of the exoY and exoF genes function in the addition of the first sugar, galactose, to the lipid carrier; the products of the exoA, exoL, exoM, exoO, exoU, and exoW genes function in subsequent sugar additions; and the product of the exoV gene functions in the addition of pyruvate. The products of the exoP, exoQ, and exoT genes are required for polymerization of the octasaccharide subunits or transport of the completed polymer. PMID- 8343956 TI - The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. AB - We have immunolabeled human and mouse metaphase chromosomes with antibodies specific for the acetylated isoforms of histone H4. All chromosomes were labeled in regions corresponding to conventional R bands (regions enriched in coding DNA), except for a single chromosome in female cells, which was largely unlabeled and which we have identified as the inactive X (Xi). Three sharply defined immunofluorescent bands, enhanced by butyrate pretreatment, were observed in homologous positions on the human and mouse Xi, showing limited, regional persistence of H4 acetylation. Two of these bands are in cytogenetic regions known to contain genes expressed on Xi. We propose that H4 hyperacetylation defines regions of the genome containing potentially transcriptionally active chromatin, while virtual absence of H4 acetylation defines both constitutive and facultative heterochromatin. PMID- 8343957 TI - Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L methionine. AB - The first three-dimensional structure of a DNA methyltransferase is presented. The crystal structure of the DNA (cytosine-5)-methyltransferase, M.HhaI (recognition sequence: GCGC), complexed with S-adenosyl-L-methionine has been determined and refined at 2.5 A resolution. The core of the structure is dominated by sequence motifs conserved among all DNA (cytosine-5) methyltransferases, and these are responsible for cofactor binding and methyltransferase function. PMID- 8343958 TI - Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. AB - The signal elicited by the interaction of odorous ligands with receptors on olfactory sensory neurons must be decoded by the brain to determine which of the numerous receptors have been activated. We have examined the patterns of odorant receptor expression in the rat olfactory epithelium to determine whether the mammalian olfactory system employs spatial segregation of sensory input to encode the identity of an odorant stimulus. In situ hybridization experiments with probes for 11 different odorant receptors demonstrate that sensory neurons expressing distinct receptors are topologically segregated into a small number of broad, yet circumscribed, zones within the olfactory epithelium. Within a given zone, however, olfactory neurons expressing a specific receptor appear to be randomly distributed, rather than spatially localized. The complex mammalian olfactory system may therefore compartmentalize the epithelium into anatomically and functionally discrete units, such that each zone expresses only a subset of the entire receptor repertoire. PMID- 8343959 TI - Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor. AB - The Notch gene of Drosophila plays an important role in cell fate specification throughout development. To investigate the functions of specific structural domains of the Notch protein in vivo, a series of deletion mutants have been ectopically expressed under the hsp70 heat shock promoter. Two classes of dominant phenotypes are observed, one suggestive of Notch loss-of-function mutations and the other of Notch gain-of-function mutations. Dominant activated phenotypes result from overexpression of a protein lacking most extracellular sequences, while dominant negative phenotypes result from overexpression of a protein lacking most intracellular sequences. These results support the notion that Notch functions as a receptor whose extracellular domain mediates ligand binding, resulting in the transmission of developmental signals by the cytoplasmic domain. Finally, the phenotypes observed suggest that the cdc 10/ankyrin repeat region within the intracellular domain plays an essential role in the postulated signal transduction events. PMID- 8343960 TI - Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. AB - The lin-12 gene of C. elegans and the Notch gene of D. melanogaster encode structurally related transmembrane proteins that mediate intercellular signaling. We show that truncated forms of these proteins consisting of only the intracellular domains cause cell fate transformations associated with constitutive activity in their respective organisms. This activity does not depend on endogenous gene function. Our results indicate that the intracellular domains of Lin-12 and Notch have intrinsic activity and that the principal role of the extracellular domains in the intact proteins is to regulate this activity. Our results also suggest that equivalent truncated forms of lin-12/Notch family members in vertebrates, including known oncogenes, are similarly active. PMID- 8343961 TI - Down-regulation of the Drosophila morphogen bicoid by the torso receptor-mediated signal transduction cascade. AB - Anterior body pattern in Drosophila is specified by the graded distribution of the bicoid protein (bcd), which activates subordinate genes in distinct anterior domains. Subsequently, transcription of these target genes is repressed at the anterior pole owing to the activity of the receptor tyrosine kinase torso (tor). We show that both activation by bcd and repression by tor can be reproduced by a minimal promoter containing only bcd-binding sites upstream of a naive transcriptional start site. Repression requires the D-raf kinase and is associated with phosphorylation of bcd protein. Repression does not require either tailless or huckebein, which were previously thought to constitute the sole zygotic output of the tor signaling system. Finally, addition of a heterologous transcriptional activation domain to bcd renders the protein insensitive to tor-mediated repression. We propose that phosphorylation resulting from the activity of the tor signal transduction cascade down-regulates transcriptional activation by the bcd morphogen. PMID- 8343962 TI - Fission yeast cut5+, required for S phase onset and M phase restraint, is identical to the radiation-damage repair gene rad4+. AB - Fission yeast cut5 mutants cause cytokinesis in the absence of normal nuclear division. We show here that cut5+ is required for both the onset of S phase and the restraint of M phase before the completion of S phase. The primary defects in cut5 mutants occur prior to S phase, but cells suffer lethal damage during M phase. Mitosis and cytokinesis occur in the presence of hydroxyurea or in the double mutant cdc10-cut5 (the cdc10 mutation alone blocks progression from G1 to S). Gene cloning shows that cut5+ is identical to the fission yeast rad4+ gene, which is similar to human XRCC1. The rad4+/cut5+ gene is unique in its positive role for replication/repair and in its negative role for mitosis/cytokinesis. We propose a single/twin chromatid marking model for rad4+/cut5+ function in cell cycle control. PMID- 8343963 TI - Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. AB - Mice with mutations at the microphthalmia (mi) locus have some or all of the following defects: loss of pigmentation, reduced eye size, failure of secondary bone resorption, reduced numbers of mast cells, and early onset of deafness. Using a transgenic insertional mutation at this locus, we have identified a gene whose expression is disrupted in transgenic animals. This gene encodes a novel member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein family of transcription factors, is altered in mice carrying two independent mi alleles (mi and miws), and is expressed in the developing eye, ear, and skin, all anatomical sites affected by mi. The multiple spontaneous and induced mutations available at mi provide a unique biological resource for studying the role of a bHLH-ZIP protein in mammalian development. PMID- 8343964 TI - Proenzyme from of cathepsin L produced by thymic epithelial cells promotes proliferation of immature thymocytes in the presence of IL-1, IL-7, and anti-CD3 antibody. AB - A thymic epithelial cell line (TEC1-4) established from newborn mouse thymus produced a cofactor to promote proliferation of double-negative (CD4-8-) thymocytes in the presence of IL-1, IL-7, and anti-CD3 antibody. Based upon the sequence of 8 amino acid residues near the N terminal portion, the factor was identified as the mouse proenzyme form of cathepsin L which is almost identical to the rat proenzyme form of cathepsin L (95% in homology). Production of the proenzyme form of cathepsin L was confirmed in the TEC1-4 and mouse embryonic thymus by Western blotting analysis and Northern blotting analysis. Furthermore, immunohistologically, the presence of cathepsin L was observed in the epithelial cells of the subcapsular layer and around the small vessels in the thymic cortex. It has been concluded that a subpopulation of thymic cortical epithelial cells produces the proenzyme form of cathepsin L which can act as a cofactor to promote proliferation of DN immature thymocytes. PMID- 8343965 TI - Antigen-specific suppressor factors of noncytotoxic CD8+ suppressor T cells downregulate antibody responses also to unrelated antigens when the latter are presented as covalently linked adducts with the specific antigen. AB - We had previously shown (i) that conjugates of a given antigen A (AgA) and monomethoxypolyethylene glycol (mPEG) induced AgA-specific tolerance in mice which was mediated by polyclonal CD8+ suppressor T (Ts) cells, as well as by soluble factor(s) of these cells (TsF), and (ii) that clones of nonhybridized CD8+ Ts cells could be derived from the above single cells, and monoclonal AgA specific TsF could be released from these cloned cells. In the present study, we demonstrate that mice pretolerized by injection of AgA(mPEG)n are also unresponsive to an unrelated antigen B (AgB), or to its haptenated derivative AgB Hpn, when AgB or AgB-Hpn is injected in the form of a covalent adduct with AgA, i.e., AgA-AgB or AgA-AgB-Hpn, but not when it is injected as a mixture with AgA; in this study human (myeloma) IgG (HIgG) served as AgA, and ovalbumin (OVA) or OVA-DNP3 served as AgB or AgB-Hpn. Moreover, this phenomenon was reproduced in vitro; i.e., Ts cells of mice tolerized with HIgG(mPEG)30, or the soluble monoclonal TsF of cloned Ts cells, exerted their associative suppressive effector function--in the obligatory presence of CD8+ T cells of syngeneic naive mice (Tn cells)--on antibody (Ab) formation to an Hp (DNP), when the Hp was present as a covalent adduct linked either directly to HIgG (e.g., HIgG-DNP7) or indirectly via OVA (as in HIgG-OVA-DNP3); however, no suppression of the anti-DNP Ab response was observed when OVA-DNP3 was present as a mixture with HIgG. Furthermore, it was established that the accessory cells involved in processing the specific Ag in the presence of the Ts cells were also downregulated, as reflected by their reduced capacity for presentation of the Ag to HIgG-specific helper T (Th) cells in proliferation assays. All these results demonstrate that (i) the phenomenon of linked immunological suppression may involve the downregulation of Th cells which recognize, concomitantly with the Ts cell, the appropriate epitopes of AgA and AgB on the same Ac cell, (ii) the downregulation of these Th cells may be a consequence of the downregulation of Ac cells by Ts cells interacting with the appropriate epitope(s) present on the Ac cells, and (iii) most remarkably the CD8+ Ts cells could be substituted by Tn cells "armed" with the specific monoclonal TsF. PMID- 8343967 TI - Low-dose streptozotocin-induced diabetes in mice. I. Course of Candida albicans infection. AB - Diabetic patients are highly susceptible to microbial and fungal infections. To better understand the immune mechanisms underlying the diabetic host-parasite relationship, we studied the course of systemic infection with Candida albicans in mice with low-dose streptozotocin-induced diabetes. For this purpose, we used a low-pathogenic strain of C. albicans, PCA-2, which causes a chronic infection in the intact host. Injection of PCA-2 cells into diabetic mice caused a lethal acute infection. The levels of interferon-gamma (IFN-gamma) determined in sera and splenocyte culture supernatants from diabetic mice were significantly higher than those in control mice. Moreover, splenic macrophages from diabetic mice were functionally activated relative to normal macrophages, as evaluated by significantly augmented C. albicans killing in vitro. However, when diabetic mice were infected with PCA-2, IFN-gamma levels dropped dramatically to undetectable levels during the first week of infection and there was a marked decrease in macrophage activation. These data suggest that the levels of IFN-gamma production early in infection might have a crucial role in generating the susceptibility of diabetic mice to infection. PMID- 8343968 TI - Reproducible procedures for establishing mouse thymic stromal cell lines. AB - Mouse thymic epithelial cell lines (MTEC) were established from Day 14-18 fetal thymus by two novel protocols. The first protocol involved the selection of TEC by the formation of complexes with adult thymocytes after transformation with the helper-free Ad5.SVR4 recombinant virus. The second protocol involved the stimulation and selection of TEC in Ca(2+)-free medium by the formation of complexes with Day 14 fetal thymocytes. The resulting TECs formed several types of thymic epithelial clusters to which Day 14 fetal thymocytes could bind. Many of these fetal thymocytes could deeply infiltrate, colonize, and proliferate within the clusters of NCAM(high) LFA-1(low) TEC (MTSC-0420-1.4, MTSC-0420-1.5, and MTSC-0613-1.2 clusters), whereas very few could infiltrate the clusters of NCAM(low) LFA-1(high) TEC (MTSC-0531-5.1 and MTSC-0531-5.2) and none bound to or infiltrated an NCAM(neg) fibroblast cluster (MTSC-fibro.). Hence, it is possible that the NCAM-positive epithelial cell lines are derived from the thymus cortex, where they may play an important role in intrathymic migration and the clonal growth of pro-T cells in fetal thymus. PMID- 8343966 TI - Differential effects of interleukin-2 and CD3 triggering on cytokine gene transcription and secretion in cultured tumor infiltrating lymphocytes. AB - The therapeutic potential of tumor-infiltrating lymphocytes (TIL) is currently under investigation. TIL have been reported to display characteristic functional defects, including impairments of activation mechanisms. In animal models, therapeutic efficacy of adoptive TIL transfer has been correlated with their capacity to produce cytokines rather than with their in vitro cytotoxic potential. In this work we assayed cytokine gene transcription and protein production in eight cultured TIL populations stimulated with recombinant human IL 2 (rhIL-2), solid-phase-bound anti-CD3 monoclonal antibodies (mAb), or a combination of the two. By using a sensitive reverse polymerase chain reaction technique, we observed that transcription of IL-5, GM-CSF, and TNF-alpha could be detected in unstimulated, IL-2-starved TIL from all cultures, while IL-4 and IFN gamma genes were found to be transcribed in two cultures out of eight. A 50 U/ml dose of rhIL-2 was sufficient to induce IL-4 and IFN-gamma gene transcription in the remaining six cultures and in four more TIL populations, respectively. In contrast, rhIL-2 could not induce IL-2 gene transcription in five of eight TIL cultures. Furthermore, it could not induce IL-10 gene transcription in any TIL population. Anti-CD3 mAb triggering, however, induced transcription of all these cytokine genes. On the other hand, IL-6, IL-7, or TGF-beta 2 gene transcription could not be induced by any of the stimuli used, including the combination of anti-CD3 and rhIL-2. Despite detection of their gene transcripts, GM-CSF, IFN gamma, or TNF-alpha was never detectable, at the protein level, in unstimulated TIL. Stimulation by rhIL-2 induced GM-CSF secretion, albeit to different extents, in all TIL populations. In contrast, rhIL-2 induced IFN-gamma and TNF-alpha production in three and one TIL population, respectively. CD3 triggering however, induced cytokine production in all TIL populations. Addition of rhIL-2 significantly increased production of GM-CSF, but not of IFN-gamma and TNF-alpha. These data underline that stimulation with a moderate dose of rhIL-2 reveals considerable heterogeneity of TIL populations regarding cytokine gene transcription and secretion. On the other hand, triggering of the CD3-T-cell receptor complex induces transcription of an extended panel of cytokine genes in all TIL populations and secretion of GM-CSF, IFN-gamma and TNF-alpha in virtually all cultures. Thus, if stimulated by properly presented antigenic peptides, TIL are capable of mounting an efficient response in terms of cytokine gene expression and protein production. PMID- 8343969 TI - Enzymes Interacting with Organophosphorus Compounds. Proceedings of 2nd International Meeting. Salsomaggiore, Italy, April 21-24, 1992. PMID- 8343970 TI - Biopolymer metal catalysts for the hydrolysis of nerve gases. AB - Glucosamine oligomers--monomer through tetramer--form complexes with Cu2+ that catalyse the hydrolysis of the 'nerve gas' 1,2,2-trimethylpropyl- methylphosphonofluroidate (soman) by cleaving the P-F bond. A 1/1 glucosamine/Cu2+ ratio whether as glucosamine or glucosamine units, gives the highest hydrolytic rate over the 11.5/1 to 1/1 range. This trend also appears to hold for a glucosamine polymer, chitosan, which, when complexed with Cu2+ also hydrolyzes soman. The relatively low rate of hydrolysis by this polymer-Cu2+ complex, while not yet explainable, is consistent with an extrapolation of the monomer-through-tetramer series. The question may be raised as to whether these biopolymer metal complexes provide any clues to the involvement of Mn2+ in the functioning of one class of P-F cleaving enzymes. PMID- 8343971 TI - The kinetics of O-hexyl O-2,5-dichlorophenyl phosphoramidate hydrolysing activity in hen plasma. AB - The organophosphorus (OP) compound O-hexyl-O-2,5-dichlorophenyl phosphoramidate (H-DCP) is hydrolysed in the plasma, liver and brain of hens and rats. We study in hen plasma the effect of tissue and substrate concentrations and of pH on the hydrolysing activity of H-DCP. The data on each tissue concentration were fitted to a double exponential mathematical model. The kinetics of this activity was not linear; in a first exponential component or fast initial phase (k1 = (1.603 +/- 0.248) x 10(-3) min-1/microliter plasma (n = 4, S.E.)) about 15% of the total compound was hydrolysed, followed by a slow second phase (k2 = (0.144 +/- 0.026) x 10(-3) min-1/microliter plasma (n = 4, S.E.)) in which the remaining 85% was hydrolysed. Both constants increased in value with pH. The hydrolytic activity and rate constants increased with the amount of plasma, but no change in kinetics was observed. The kinetic data are discussed in terms to lend support to the hypothesis of a stereospecific degradation of H-DCP. PMID- 8343972 TI - Stereo-specific degradation of the R-(+) isomer of O-n-hexyl-S methylphosphorothioamidate catalysed by rabbit serum. AB - Resolved isomers of O-n-hexyl-S-methylphosphorothioamidate (HXM) which had been synthesised by separate stereospecific routes were analysed by chiral glc: about 2-3% of R-(+) isomer was found in the S-(-) sample and accounted for nearly all the inhibitory power against neuropathy target esterase. Incubation of racemic HXM with rabbit serum led to slow but very specific disposal of R-(+) isomer to undetectable levels with very slight loss of S-(-): the rate of disposal was roughly estimated to be about 1% of the published rate of hydrolysis of paraoxon. Incubation with crystalline chymotrypsin caused a preferential but not totally selective disposal of S-(-) isomer. PMID- 8343973 TI - Recommendations of the IUBMB Nomenclature Committee: comments concerning classification and nomenclature of esterases hydrolysing organophosphorus compounds. PMID- 8343974 TI - Peripheral esterases in the rat: effects of classical inducers. AB - Liver microsomal paraoxonase, aryl esterase and fluazifop butyl esterase (carboxylesterase) were induced by pretreatment of rat with phenobarbitone but not by beta-naphthoflavone or clofibric acid. In the extrahepatic tissues lung cytosolicfluazifop butyl and phenylacetate esterase were induced. PMID- 8343975 TI - Three-dimensional structure of acetylcholinesterase and of its complexes with anticholinesterase drugs. AB - Based on our recent X-ray crystallographic determination of the structure of acetylcholinesterase (AChE) from Torpedo californica, we can see for the first time, at atomic resolution, a protein binding pocket for the neurotransmitter, acetylcholine. It was found that the active site consists of a catalytic triad (S200-H440-E327) which lies close to the bottom of a deep and narrow gorge, which is lined with the rings of 14 aromatic amino acid residues. Despite the complexity of this array of aromatic rings, we suggested, on the basis of modelling which involved docking of the acetylcholine (ACh) molecule in an all trans configuration, that the quaternary group of the choline moiety makes close contact with the indole ring of W84. In order to study the interaction of AChE with anticholinesterase drugs at the structural level, we have incorporated into the acetylcholinesterase crystals several different inhibitors, and have recently determined the 3-D structure of AChE:edrophonium and AChE:tacrine complexes. The crystal structures of both of these complexes are in good agreement with our model building of the ACh bound in the active site of AChE and indicate the interactions of these two drugs with the enzyme. PMID- 8343976 TI - Structure and regulation of expression of the acetylcholinesterase gene. AB - Acetylcholinesterase, an enzyme essential for the termination of the action of acetylcholine, is encoded by a single gene. Alternative mRNA processing gives rise to the expression of enzyme forms with three distinct carboxyl-termini. These structural differences govern the cellular disposition of the expressed enzyme but do not influence catalytic activity. Alternative polyadenylation signals give rise to distinct 3' non-coding regions which are likely to affect mRNA stability. Alternative splicing also occurs at the 5' end of the gene where two promoter regions can be identified. Hence, regulation of expression of the gene occurs at 3 levels, transcriptional through alternative promoters, translational by affecting mRNA stability and processing of distinct mRNAs and post-translationally by giving rise to distinct peptide chains which are processed differently. Recombinant DNA studies have also been extended to modifying protein structure through site-specific mutagenesis and studying the function of the mutant enzymes. PMID- 8343977 TI - Molecular dissection of cholinesterase domains responsible for carbamate toxicity. AB - Carbamate compounds marked for their cholinesterase (ChE) inhibition are widely used as therapeutics and as insecticides. Groups of closely related carbamate molecules provide an important tool in the understanding of the domains responsible for binding these ligands to ChEs. Comparative inhibition profiles were derived for five N-methyl carbamates, mostly carbofuran derivatives, differing in length and branching of their hydrocarbonic chain towards human erythrocyte acetylcholinesterase (H.AChE), human serum butyrylcholinesterase (H.BChE) in its normal form or in a mutant form containing the point mutation Asp70-->Gly, and Drosophila nervous system ChE. Carbofuran was more toxic to all three ChEs than any of the other derivatives, with IC50 values which differed by more than 1000-fold. Drosophila ChE appeared to be most sensitive to all of the examined carbamates, and H.AChE was consistently more sensitive than H.BChE. Moreover, inhibition efficiency for H.BChE decreased more effectively than it did for H.AChE with increased length and complexity of the side chain, indicating less flexible carbamate binding site in BChE as compared with AChE. The Asp70- >Gly mutation had no apparent effect on H.BChE inhibition by N-methyl carbamates, suggesting that the Asp70 domain localized near the rim of the active site groove is not important in carbamate binding. Comparison of the carbamate IC50 values with published LD50 values demonstrated correlation between the in vivo toxicity and inhibition of BChE by carbamates, suggesting a biological in addition to scavenging importance for BChE in mammals. Pinpointing different domains characteristic of carbamate binding in each member of the ChE family can thus shed light on the variable toxicity of these inhibitors to insects and mammals, predict the toxicity of yet untested inhibitor molecules and help in designing novel and improved ChE inhibitors. PMID- 8343978 TI - Organophosphate sensitive and insensitive carboxylesterases in human skin. AB - The influence of paraoxon and bis(4-nitrophenyl)phosphate (BNPP) on carboxylesterases of human skin is assayed. Both organophosphates have frequently been used as inhibitors of carboxylesterases of the B-esterase type. Homogenates from carefully washed skin have no paraoxon-cleaving activity and very little phosphodiesterase activity with BNPP. However, a number of skin enzymes are irreversibly inhibited by these compounds. Three zones of carboxylesterase bands can be detected in the soluble fraction of skin homogenate by isoelectric focusing. One zone containing 5 esterase bands in the pI-range of 6.7-7.0 and another zone at pI 4.9 are insensitive to organophosphate inhibition. The zone with the main esterase activities contains at least 6 bands in the range of pI 5.7-6.2. All of these are quickly and completely inhibited by paraoxon. The complex inhibition kinetics with BNPP and observations with differing substrates point to a functional heterogeneity. The esterases with pI-values in the range of 5.7 to 6.2 and the esterase with pI 4.9 can be enriched using anion exchange chromatography and FPLC. From the data presented here it is concluded that human skin contains at least four different carboxylesterases which act on simple aromatic esters. PMID- 8343979 TI - Drosophila acetylcholinesterase: mechanisms of resistance to organophosphates. AB - Quantitative and qualitative changes of acetylcholinesterase can affect the sensitivity of insects to insecticides. First, the amount of acetylcholinesterase in the central nervous system is important in Drosophila melanogaster, flies which overexpress the enzyme are more resistant than wild-type flies. On the contrary, flies which express low levels of acetylcholinesterase are more susceptible. An overproduction of acetylcholinesterase outside the central nervous system also protects against organophosphate poisoning, that is, flies producing a soluble acetylcholinesterase, secreted in the haemolymph, are resistant to organophosphates. Second, resistance can also result from a qualitative modification of acetylcholinesterase. Four mutations have been identified in resistant strains: Phe115 to Ser, Ileu199 to Val, Gly303 to Ala and Phe368 to Tyr. Each of these mutations led to a different pattern of resistance and combinations between these mutations led to highly resistant enzymes. PMID- 8343981 TI - Synthesis of the DNA probe for the determination of rat AChE mRNA. AB - This is a preliminary report on our attempts of synthesis by polymerase chain reaction (PCR), the cDNA probe for the determination of mRNA of the AChE catalytic subunit. As our strategy we took the advantage of the fact that sequence identity of AChE gene increases with phylogenetic proximity. Single codon usage could therefore be applied. Two non-degenerate PCR primers were synthesised corresponding to AChE regions which were highly conservative among species analyzed until now. The sequence amplified by these two primers should be 339 base pairs long as concluded from mouse AChE sequence. By determining the nucleotide sequence of the PCR product and by comparison of this sequence with the corresponding mouse AChE region, we would be able to verify the correspondence of our PCR product to the rat AChE gene fragment. Only the first four amino acids of our PCR product flanking Phe 200, which is the first amino acid from the A2 primer, are 100% homologous with the mouse AChE. However, from the next 18 amino acids towards the N-terminal, only 4 are homologous with the mouse AChE. Since we expected more than 90% homology between the phylogenetically closely related species of mouse and rat, we doubt that the DNA sequence obtained belongs to the rat AChE gene. PMID- 8343980 TI - Computerized analysis of covalent inhibition kinetics for identification of heart muscle cholinesterase and brain carboxylesterase isoenzymes. Design of differential inhibition assays. AB - The kinetics of time- and concentration-dependent covalent organophosphorus inhibition of carboxylesterase isoenzymes (EC 3.1.1.1) and cholinesterase isoenzymes (EC 3.1.1.7 and EC 3.1.1.8) were investigated using a wide range of organophosphate inhibitor concentrations (10(-10)-10(-3) mol/l) and different inhibition times. Computerized analysis of inhibition curves by weighted non linear least-squares curve fitting was compared to graphic analysis by iterative elimination of exponential functions. Possible experimental errors due to inhibitor saturation kinetics and enzymatic organophosphate hydrolysis were thoroughly investigated. In mammalian heart muscle, three different cholinesterase isoenzymes were identified. High sensitivity and specificity of the classic differential inhibition test for carboxylesterase activity of hen brain neuropathy target esterase (NTE) could be confirmed independently with both methods of inhibition curve analysis. PMID- 8343982 TI - The influence of chronic treatment with dexamethasone on the acetylcholinesterase activity in rat skeletal muscle. AB - In the conditions of chronically elevated glucocorticoid agents in plasma, a drop in AChE activity of about 45% was reported. This data suggests the possibility that among other factors glucocorticoids also control AChE activity in the skeletal muscles. The question addressed in the present investigation was if AChE activity was reduced uniformly or selectively in the rat skeletal muscles after chronic application of dexamethasone? Selective effects of glucocorticoids on the AChE activity in different muscles and/or different types or regions of muscles would suggest the potential of these agents to regulate AChE metabolism in the skeletal muscle according to the environmental demands. Specific activity of skeletal muscle AChE was reduced in sternomastoideus (SM), extensor digitorum longus (EDL) and diaphragm (D) but not in soleus (SOL) after chronic dexamethasone treatment. Axial SM (white part) was more affected than distal white muscle EDL. AChE was better preserved in red rather than in white parts of muscles. The endplate-free region lost twice as much of specific AChE activity than the endplate-rich region. Our results suggest, but do not prove that glucocorticoid agents act in a selective way on the AChE metabolism of the skeletal muscles. PMID- 8343983 TI - The effects of pretreatment with soman simulator in the skeletal muscle: direct interactions with acetylcholinesterase. AB - Soman simulator PDP is a compound that has a chemical structure identical to soman, except that the fluorine atom is replaced by a methyl group which makes PDP unable to bind covalently to the AChE active center. In rats, late mortality observed after treatment with high doses of soman could be prevented by PDP pretreatment. Such pretreatment has been much less efficient in primates. The effect of PDP in rats has been explained by blocking the deposition of soman in so-called soman depots in which soman is stored intact and subsequently released. In this paper we demonstrate that in the presence of PDP, inhibition of rat muscle AChE by soman is reduced in rat but not in human muscle homogenates. This result suggests that at least part of the beneficial effects of PDP pretreatment in rat might be due to the direct interaction of PDP with AChE resulting in reduced AChE phosphorylation by soman. PMID- 8343984 TI - Sheep brain pseudocholinesterase: inhibition kinetics of the partially purified enzyme by some substrate analogues. AB - Pseudocholinesterase (ChE) (acylcholineacylhydrolase, EC 3.1.1.8) has been partially purified (about 270-fold) from sheep brain. The procedure included ammonium sulfate fractionation (20-80%), DEAE-Trisacryl M chromatography and procainamide-Sepharose 4B affinity chromatography. The molecular weight of purified ChE was found to be 290,000 by gel filtration. Kinetic properties of the enzyme have been studied using the substrate analogues choline, succinylcholine and benzoylcholine. It was shown that the inhibition was partially competitive. PMID- 8343985 TI - Rapid potentiometric determination of cholinesterases in plasma and red cells: application to eptastigmine monitoring. AB - Eptastigmine (MF 201) is a new physostigmine derivative with potent inhibitory activity on cholinesterases. Here we present a new potentiometric cholinesterase activity assay suitable for MF 201 monitoring. The analysis is performed on a differential pH system and has the following characteristics: (a) within-run precision: C.V. 2.0% (plasma cholinesterase), 1.8% (red cell cholinesterase); (b) between-run precision: C.V. 4.0% (plasma cholinesterase); (c) linearity: 1-10 kU/l (plasma cholinesterase), 6-70 U/g Hb (red cell cholinesterase); (d) comparison with a reference method (x, HITACHI 737 Boerhinger Mannheim, Italy): y = 0.785x - 0.07; n = 37; r = 0.998. The assay has been applied to the determination of plasma and red cell cholinesterase activity in volunteers over 60 years of age treated with a single oral dose of 30 mg eptastigmine. We found that red cell cholinesterase is selectively inhibited after MF 201 administration with the following kinetics (time, % of inhibition, mean +/- S.E., n = 6): 0 h, 0; 1 h, 17 +/- 4.6; 2 h, 24 +/- 4; 4 h, 23 +/- 4.4; 12 h, 14 +/- 3. Eptastigmine plasma levels were also determined by a HPLC method: maximum concentration was found one hour after drug administration. PMID- 8343986 TI - Cholinesterases as scavengers for organophosphorus compounds: protection of primate performance against soman toxicity. AB - The present treatment for poisoning by organophosphates consists of multiple drugs such as carbamates, antimuscarinics, and reactivators in pre- and post exposure modalities. Recently an anticonvulsant, diazapam, has been included as a post-exposure drug to reduce convulsions and increase survival. Most regimens are effective in preventing lethality from organophosphate exposure but do not prevent toxic effects and incapacitation observed in animals and likely to occur in humans. Use of enzymes such as cholinesterases as pretreatment drugs for sequestration of highly toxic organophosphate anticholinesterases and alleviation of side effects and performance decrements was successful in animals, including non-human primates. Pretreatment of rhesus monkeys with fetal bovine serum acetylcholinesterase protected them against lethal effects of soman (up to 5 LD50) and prevented signs of OP toxicity. Monkeys pretreated with fetal bovine serum acetylcholinesterase were devoid of behavioral incapacitation after soman exposure, as measured by serial probe recognition or primate equilibrium platform performance tasks. Use of acetylcholinesterase as a single pretreatment drug provided greater protection against both lethal and behavioral effects of potent organophosphates than current multicomponent drug treatments that prevent neither signs of toxicity nor behavioral deficits. Although use of cholinesterases as single pretreatment drugs provided complete protection, its use for humans may be limited, since large quantities will be required, due to the approximately 1:1 stoichiometry between organophosphate and enzyme. Bisquaternary oximes, particularly HI-6, have been shown to reactivate organophosphate-inhibited acetylcholinesterase at a rapid rate. We explored the possibility that enzyme could be continually reactivated in animals pretreated with fetal bovine serum acetylcholinesterase, followed by an appropriate dose of reactivator, and challenged with repeated doses of sarin. In in vitro experiments, stoichiometry greater than 1:400 for enzyme:sarin was achieved; in vivo stoichiometry in mice was 1:65. Pretreatment of mice with fetal bovine serum acetylcholinesterase and HI-6 amplified the effectiveness of exogenous enzyme as a scavenger for organophosphate. PMID- 8343987 TI - Role of carboxylesterases in the prevention and potentiation of N-methylcarbamate toxicity. AB - Pretreatment of rats with iso-OMPA one hour prior to each of the N methylcarbamate insecticides, carbofuran, propoxur, or aldicarb, potentiated the toxicity of these carbamates threefold. None of these compounds alone in the dosage used produced toxic signs; however, carboxylesterase (CarbE) activity in a variety of organs including brain, muscle, liver, and plasma was significantly reduced, while acetylcholinesterase (AChE) activity was unchanged. Significant inhibition of AChE was observed after the combination of tetraisopropylpyrophosphoramide (iso-OMPA) with each one of these N methylcarbamates. It is suggested that CarbEs are more sensitive than AChE to these N-methylcarbamates and inhibition of CarbE by iso-OMPA raises the concentration of N-methylcarbamates available to inhibit AChE resulting in increased toxicity. Other N-methylcarbamates such as physostigmine do not inhibit CarbE, nor are their toxicities potentiated by iso-OMPA. PMID- 8343988 TI - Diethylphosphorus metabolites in serum and urine of persons poisoned by phosalone. AB - The presence and elimination rate of phosalone and its diethylphosphorus metabolites in blood serum and urine were studied in persons who had ingested a concentrated phosalone solution. Phosalone was detected only in serum samples. As it was rapidly hydrolysed and eliminated from the body, its diethylphosphorus metabolites were a more sensitive indicator of exposure. The concentration decrease of phosalone in serum and of total diethylphosphorus metabolites in serum and urine followed the kinetics of a biphasic reaction. The faster elimination half-times in serum, calculated for two persons, were 2.3 and 3.4 h for phosalone and 3.4 and 38.6 h for total diethylphosphorus metabolites. In the faster phase the average elimination half-time of total urinary metabolites in five persons was 25 +/- 17 h. The kinetic data for total urinary metabolites in a person occupationally exposed to phosalone indicated an early and very fast elimination phase (elimination half-time 1.3 h), which was overlooked in poisoned persons. The proportions of single metabolites in total urinary metabolites in poisoned persons depended on whether the total amount of diethylphosphorus metabolites was above 1000 or below 1000 nmol/mg creatinine. Diethylphosphorodithioate predominated at high and diethylphosphate at low concentrations of total metabolites. The correlation between the maximum concentrations of total metabolites, measured in urine of poisoned persons on the day of admission to hospital or a day later, and the initial depression of serum cholinesterase (EC 3.1.1.8) and erythrocyte acetylcholinesterase (EC 3.1.1.7) activities was poor (r = 0.6). PMID- 8343989 TI - Interaction of imidazolium and pyridinium dioximes with human erythrocyte acetylcholinesterase. AB - Two pyridinium and two imidazolium dioximes were tested as reversible inhibitors of human erythrocyte acetylcholinesterase (AChE), as protectors of the enzyme against phosphorylation and as reactivators of the phosphorylated AChE. All four dioximes reversibly inhibited AChE, protected the enzyme against phosphorylation by soman and tabun and reactivated AChE after phosphorylation by sarin, VX and tabun. From the experimental results the enzyme/dioxime dissociation constants were evaluated for the catalytically active enzyme and for phosphorylated enzyme. The evaluation constants have shown that all four dioximes have about the same affinity for the catalytically active as for the phosphylated AChE. Obtained results also indicate that imidazolium dioximes probably bind only to the allosteric, while pyridinium dioximes bind to both, the catalytic and the allosteric site of the enzyme. PMID- 8343990 TI - Avian serum esterases: species and temporal variations and their possible consequences. AB - Avian serum esterases are predominantly of the 'B' type (cholinesterases and carboxylesterases) and are inhibited by carbamates and the 'active' oxon forms of organophosphorus pesticides. Selective inhibition of mammalian serum carboxylesterase, a 'B' esterase, has shown that this enzyme may play an important role in detoxication by irreversibly binding, and thus inactivating, anticholinesterase compounds. Studies have shown differences between carnivorous and omnivorous/herbivorous avian species in the level of activity and range of forms of carboxylesterases and cholinesterases in sera. In addition, these enzymes show seasonal, diurnal and developmental variations in activity. This paper will discuss species and temporal variations in avian serum 'B' esterases in relation to their possible influence on pesticide toxicity. PMID- 8343991 TI - Symposium introduction: retrospect and prospects for neuropathy target esterase (NTE) and the delayed polyneuropathy (OPIDP) induced by some organophosphorus esters. AB - This article introduces a Symposium devoted to Neuropathy Target Esterase (NTE). The characteristics of the disorder known as OPIDP are described and the steps by which NTE was identified as the target are summarised. Studies with many organophosphates, phosphinates and chiral phosphonates are entirely consistent with a 2-step process of initiation referred to as 'NTE (70-80%) aging': about 70 80% of available nervous system NTE is first covalently phosphylated causing inhibition of esterase activity, and then the molecules of inhibited NTE undergo a covalent bond-cleavage leaving a negative charge in the region of the still bound phosphorus. This understanding has clarified structure/activity studies of neuropathic potential of OP esters and is now routinely applied in toxicological evaluations for regulatory purposes. However, the biological function of NTE has remained a mystery. Prospective views of the role of NTE are presented by different authors. Attempts to isolate catalytically active or radiolabelled inhibited NTE are near to success. Since the Symposium, complete isolation of NTE affinity-purified from hen brain has been reported (see M.K. Johnson & P. Glynn, Toxicologist, 13 (1993) 211, Abstr. 773). Some minor, but possibly significant, differences in properties of a soluble and a membrane-bound form of NTE in sciatic nerve has been identified. The nature of the disturbance brought about by covalent binding of organophosphoramidates at the active site of NTE and the discovery that 'non-aging' inhibitors of NTE can promote neuropathy in hens given a sub-neuropathic dose of neuropathic OPs has led to a concept of NTE inhibitors having a range of 'partial agonist' effects at the covalent binding site. Evidence is emerging that the promotion target may be 'cousin-of NTE' with very similar inhibition characteristics and a function in the processes of response to or repair of axonal damage. PMID- 8343993 TI - Molecular characterisation of neuropathy target esterase: proteolysis of the [3H]DFP-labelled polypeptide. AB - Neuropathy target esterase (NTE) in hen brain membranes can be labelled with tritiated di-isopropylfluorophosphate ([3H]DFP) and appears to be associated with a 155-kDa polypeptide. Using preparative SDS-PAGE, we have obtained preparations in which [3H]DFP-labelled NTE comprises 2% of the total protein. Further purification of the 155-kDa polypeptide has proved difficult. We therefore attempted to use proteases to excise smaller [3H]DFP-labelled fragments which might be more amenable to fractionation. V8 protease treatment generated a labelled fragment of about 16 kDa which could be fractionated on SDS-PAGE and contained tritium attached to both site X (putatively the active site serine) and site Z (the residue to which an isopropyl moiety is transferred during aging of [3H]DFP-inhibited NTE). Papain and thermolysin treatments generated a small labelled peptide (< 10 kDa) which could be fractionated on reverse-phase HPLC and in which tritium was attached to site X but not site Z. N-terminal sequencing of the thermolysin-generated peptide fraction indicated sample heterogeneity but also suggested that the active site of NTE may contain the serine esterase consensus sequence: Gly-Glu-Ser-Xxx-Gly. PMID- 8343992 TI - Affinity chromatography of neuropathy target esterase. AB - Neuropathy target esterase (NTE) is a membrane-bound protein which has been proposed as the target site in nerve tissue for initiation of organophosphate induced delayed neuropathy (OPIDN). Efforts to characterize NTE and to determine the mechanism of its involvement in OPIDN have been hampered by the lack of a suitable method for its purification. We describe here the development of a trifluoromethyl ketone liganded affinity gel which selectively binds NTE. Triton X-100/NaCl extracts of NTE from chick embryo brain microsomal membranes were adsorbed to an affinity gel prepared by attachment of 3(9'-mercaptononylthio) 1,1,1-trifluoropropan-2-one to epoxy-activated Sepharose CL4B (MNTFP-Sepharose). Typically 70-80% of NTE activity is bound under conditions in which undetectable quantities of total protein bound (< 4%). It proved difficult to elute active NTE under non-denaturing conditions, but SDS-PAGE analysis of MNTFP-Sepharose bound proteins eluted with 2% SDS identified a 155 kDa NTE-like protein that bound in a trifluoromethylketone- or mipafox-sensitive but paraoxon-insensitive manner. The levels of inhibition of binding correlated with the inhibition of activity and suggested that the 155-kDa band was composed of a single protein. MNTFP-Sepharose affinity chromatography in combination with preparative SDS-PAGE therefore holds promise as a method for obtaining microgram quantities of NTE for chemical analysis and sequencing. PMID- 8343994 TI - Biochemical properties and possible toxicological significance of various forms of NTE. AB - NTE (neuropathy target esterase) is considered to be the target for organophosphorus-induced delayed polyneuropathy and is operationally measured by radiolabelling or by determining its esteratic activity as the paraoxon-resistant mipafox-sensitive phosphorylable site(s). From electrophoresis and density gradient centrifugation using radiolabelling techniques, several phosphorylable sites have been described in hen brain that are paraoxon-resistant mipafox sensitive; however, only the majority electrophoresis band (155 kDa) shows properties related with the aging reaction. Kinetic criteria have also suggested two components of brain NTE (NTEA and NTEB). Most brain NTE is recovered in the particulate microsomal fraction and only about 1% in soluble fraction. In sciatic nerve about 50%/50% activity is recovered as soluble (S-NTE) or particulate (P NTE) forms. A similar distribution were observed in hen, cat, rat and young chick. The fixed time inhibition curves show that P-NTE is more sensitive to mipafox, DFP and hexyl-DCP than S-NTE, while the reverse is true for methamidophos. P-NTE fits properly to one sensitive component while S-NTE fits better to two sensitive component models, except in the case of methamidophos. In vivo, significant differences in the inhibition of P- and S-NTE by mipafox were found only when using low non-neuropathic dosing. The possible significance of different NTE forms are discussed. PMID- 8343995 TI - The cytoskeleton as a target for organophosphorus ester-induced delayed neurotoxicity (OPIDN). AB - Although the immediate action of organophosphorus esters is the inhibition of acetylcholinesterase, some of these compounds also produce a neurodegenerative disorder known as organophosphorus ester-induced delayed neurotoxicity (OPIDN). Tri-o-cresyl phosphate (TOCP) first produced this condition in humans and later in sensitive animal species. OPIDN is characterized by a delay period prior to onset of ataxia and paralysis. The neuropathologic lesions are Wallerian-type degeneration of the axon and myelin in the distal parts of the large tracts in both the central and peripheral nervous systems. In the past decade we have demonstrated that the pathognomonic features of OPIDN are an aberrant increase in autophosphorylation of calcium/calmodulin kinase II (CaM kinase II) and an increase in phosphorylation of cytoskeletal proteins, i.e., MAPs, tubulin, neurofilament triplet proteins, and myelin basic protein. Protein kinase-mediated phosphorylation of cytoskeletal proteins plays a critical role in regulating the growth and maintenance of the axon. We hypothesize that, in OPIDN, hyperphosphorylation of cytoskeletal proteins and axonal swelling are causally linked. Hyperphosphorylation of cytoskeletal proteins decreases their transport rate down the axon relative to their rate of entry into the axon, thus leading to their accumulation. Consistent with this hypothesis is our finding of the anomalous accumulation of phosphorylated neurofilament aggregates in the central and peripheral axons of hens treated with TOCP. PMID- 8343996 TI - The role of neurotoxic esterase (NTE) in the prevention and potentiation of organophosphorus-induced delayed neurotoxicity (OPIDN). AB - The first step in the initiation of organophosphorus-induced delayed neuropathy (OPIDN) is proposed to be the phosphorylation of an enzyme found in the nervous system called neurotoxic esterase (neuropathy target esterase, NTE). It has been known for over twenty years that non-neuropathic inhibitors of NTE exist and can actually prevent OPIDN when given before a neuropathic organophosphate (OP). Within the last three years it has become evident that another outcome is possible following in vivo interaction between neuropathic and nonneuropathic NTE inhibitors. When administered after OP exposure, nonneuropathic inhibitors can intensify or potentiate signs of OPIDN in adult chickens. Additionally, whereas developing chickens are typically resistant to the effects of neuropathic OPs, resistant age groups will develop OPIDN when exposure to a neuropathic OP is followed by the non-neuropathic NTE inhibitor phenylmethylsulfonyl fluoride. As in the case of prevention, studies of the potentiation of OPIDN may yield insight into mechanisms involved in the pathogenesis of delayed neurotoxicity. A brief review of current knowledge regarding the role of NTE in both the prevention and potentiation of OPIDN is presented. PMID- 8343997 TI - Properties of partly preinhibited hen brain neuropathy target esterase. AB - NTE inhibitors cause different toxicological consequences (protection, induction or potentiation/promotion of neuropathy) depending on the order of dosing. These effects might be explained in terms of several phosphorylable sites with 'allosteric irreversible' behaviour. Brain neuropathy target esterase (NTE) has been preinhibited with phenylmethylsulphonyl fluoride (PMSF) (0, 5, 10, 15, 30 and 60 microM) or with diisopropylphoshoro fluoridate (DFP) (0, 0.2, 0.5, and 1 microM) at 37 degrees C for 30 min. After washing by centrifugation, tissues were then reinhibited with a range of PMSF (0 to 80 microM) or DFP (0 to 1 microM) concentrations. The slopes of the inhibition curves (log % activity vs. concentration) of pretreated tissues were identical to those of the non pretreated tissues, with non-distinguishable I50 values. It is concluded that allosteric effects are not likely to be involved in membrane-bound NTE of hen brain. PMID- 8343998 TI - Reactivation of phosphorodiamidated acetylcholinesterase and neuropathy target esterase by treatment of inhibited enzyme with potassium fluoride. AB - It has been thought that the phosphorus-enzyme bond in inhibited esterases inhibited by such agents as mipafox (N,N'-di-iso-propylphosphorodiamidate) was refractory to reactivating agents either because an 'aging' reaction occurs soon after inhibition or because the bond was intrinsically very strong. We have found that both acetylcholinesterase (AChE) and neuropathy target esterase (NTE) which had been inhibited with either mipafox or with a di-n-butylphosphorodiamidate could be reactivated by prolonged treatment with aqueous potassium fluoride (KF): the reaction proceeded with first-order kinetics. Furthermore there was no time dependent loss of reactivatability (aging). Di-isopropylphosphoro butyrylcholinesterase could be fully reactivated by this treatment but after 18 h to allow aging the monoisopropyl phosphoro-enzyme was totally refractory to KF. We conclude that it is likely that the mipafox-enzyme bond in inhibited NTE and AChE is relatively strong but that aging has not occurred. The local disturbance around the active site of NTE caused by attachment of the phosphorodiamidate molecule appears to be sufficient to initiate delayed neuropathy without necessity for an 'aging' reaction. PMID- 8343999 TI - Relationship of neuropathy target esterase inhibition to neuropathology and ataxia in hens given organophosphorus esters. AB - Adult White Leghorn hens were acutely exposed to 3 dosages of the following organophosphorus compounds: mipafox, tri-ortho-tolyl phosphate (TOTP), phenyl saligenin phosphate, and diisopropylphosphorofluoridate (DFP). Neuropathy target esterase (NTE) activity was measured in brain and spinal cord 4 or 48 h after exposure. Ataxia was assessed using an 8-point rating scale on days 9 through 21 after administration, and neuropathological examination was conducted on samples collected from perfusion-fixed animals on day 21. Morphological alterations were indicated by lesion scores between 0 (no lesions) and 4 (diffuse involvement of spinal cord tracts and > 25% degeneration of peripheral nerve fibers). Dosages of mipafox (30 mg/kg i.p.), TOTP (500 mg/kg p.o.), phenyl saligenin phosphate (2.5 mg/kg i.m.) and DFP (1 mg/kg s.c.) that were capable of inhibiting NTE > 80% in both brain and spinal cord preceded ataxia which reached maximal levels (scores of 7-8), and development of lesions scored as 4. Hens were notably impaired (ataxia scores of 3-4) 21 days after administration of dosages of mipafox (3 and 6 mg/kg), TOTP (90 mg/kg), phenyl saligenin phosphate (0.1 and 0.2 mg/kg), and DFP (0.4 mg/kg) when spinal cord NTE was inhibited 40-75%. Lesions were, however, only noted in spinal cord and peripheral nerves of hens given TOTP or DFP (scores 1-3). These data indicate that inhibition of spinal cord NTE > 80% was predictive of severe ataxia and extensive pathology in the hen and that less NTE inhibition was indicative of less severe ataxia and a lower score for neuropathological damage. PMID- 8344000 TI - Screening of O-ethyl O-4-nitrophenyl phosphoramidate (ENPP) for delayed neuropathic potential. AB - O-Ethyl-O-4-nitrophenylphosphoramidate is a short-acting anticholinesterase and a possible candidate for a prophylactic agent against nerve agents since human acetylcholinesterase inhibited by this agent undergoes rapid spontaneous reactivation which can be accelerated further, if necessary, by treatment with oximes. Doses of the agent > 1 mg/kg (s.c.) given to unprotected rats were fatal in a short time but 2 rats and one hen given 0.5 mg/kg survived. Hens given 2.5 or 4 mg/kg s.c. 20 min after prophylactic physostigmine + atropine survived acute effects and were killed 4.5 or 24 h later. Brain and spinal cord neuropathy target esterase levels of these hens were depressed only 4-10% compared with levels in brains from hens given only oxime + atropine or of undosed animals. Clinical signs of neuropathy were not seen in surviving birds observed for 3 weeks. It appears there would be negligible delayed neuropathic hazard associated with administration of O-ethyl-O-4-nitrophenylphosphoramidate at subacute doses. PMID- 8344001 TI - The R-(+)isomer of O-n-hexyl S-methyl phosphorothioamidate causes delayed neuropathy in hens after generation of a form of inhibited neuropathy target esterase (NTE) which can be reactivated ex vivo. AB - To initiate delayed neuropathy (DN) in adult hens organophosphates and phosphonates must inhibit most neural NTE and the inhibited NTE must undergo an 'aging' reaction. Phosphinates and those chiral isomers of phosphonates which produce non-aging NTE do not cause DN but act as prophylactic agents. Some racemic phosphoramidates cause DN although the inhibited NTE in autopsy samples can be reactivated in vitro (Johnson, Read and Vilanova, 1991, Arch. Toxicol., 65, 618-624). We now report that pure R(+)isomer of O-n-hexyl S-methyl phosphorothioamidate (5-20 mg/kg per os) caused slight acute effects but typical DN associated with high inhibition of NTE in brain, spinal cord and sciatic nerve (maximum by 6-24 h): the inhibited NTE was easily reactivated by KF (presumed not aged). For each dose the average residual NTE activity in the three tissues 24 h after dosing and the clinical ataxia severity on peak days 15-17 (score out of 4) was: 5 mg/kg: 13, 14, 27% (2,2,2,1); 10 mg/kg: 10, 14, 12%, (4,3,2); 15 mg/kg: 10,11,17%, (3,3,4); 20 mg/kg: 6, 10, 8% (3,3,3,2). The ability of this isomer and of other racemic phosphoramidates to initiate DN by covalent reaction at the active site of NTE (inhibition) without subsequent aging suggests that the chemistry (? charge distribution) in the region of the phosphorus atom determines that disturbance in the molecular environment of NTE which initiates DN. PMID- 8344002 TI - Prophylaxis against and promotion of organophosphate-induced delayed neuropathy by phenyl di-n-pentylphosphinate. AB - Phenyl di-n-pentylphosphinate (PPP) is a potent inhibitor of neuropathy target esterase (NTE) with negligible effect on acetylcholinesterase: I50S at 37 degrees C for 20 min and pH 8, respectively are 0.2 microM and > 2mM. PPP is not neuropathic. This is compatible with the fact that inhibited NTE is autopsy material from hens dosed with PPP can always be reactivated in vitro, presumably because no 'aging' reaction has occurred. PPP (10 mg/kg s.c.) given to hens up to 4 days before severely neuropathic doses (1.7 mg/kg) of diisopropylphosphorofluoridate (DFP) prevented neuropathic but not cholinergic effects of DFP. Hens given PPP 3 days after a sub-neuropathic dose of DFP (0.4 mg/kg) developed severe clinical neuropathy (clinical scores of 7 and 5 compared with DFP-plus-solvent scores 0,1,3). These prophylactic and promoting effects are similar to those exerted by phenylmethanesulphonyl fluoride (PMSF) at doses which inhibit NTE. In 3 out of 4 birds a pre-dose with PMSF (15 mg/kg) prevented the promoting effect of 120 mg/kg PMSF given after DFP. PMID- 8344003 TI - Phenylmethanesulfonyl fluoride delays the recovery from crush of peripheral nerves in hens. AB - Several esterase inhibitors (carbamates, phosphinates and sulfonyl halides) have been shown to promote organophosphate-induced delayed polyneuropathy (OPIDP). The mechanism of promotion is not understood, but indirect evidence suggests impairments of peripheral nerve repair. Also, other toxic neuropathies, such as those caused by 2,5-hexanedione in hens and bromophenylacetylurea in rats, have been reported to be promoted by phenylmethanesulfonyl fluoride (PMSF). Hen sciatic nerve was crushed at the bifurcation. Either mild or heavy pressure was applied by forceps obtaining a mild and rapidly recovering lesion (possibly myelinic) or a more severe, long-lasting lesion (possibly axonal), respectively. Hens were then treated with PMSF (120 mg/kg s.c. or 200 mg/kg s.c. x 2, 24 h apart) either before (5-48 h) crush or afterwards (5-48 h). Controls received vehicle only. Animals were observed for reappearance of digit movements, and standing and walking ability. PMSF treatment did not change the clinical outcome when animals received a mild crush. In hens receiving the more severe crush the reappearance of digit movements and the complete clinical recovery were observed after 43 +/- 14 and 63 +/- 9 days, respectively. In animals treated with PMSF there was a significant delay in both reappearance of digit movements (56 +/- 11 days when PMSF was given 24 and 48 h before crush, and 55 +/- 10 days, when given 24 and 48 h after crush) and in clinical recovery (75 +/- 15 and 80 +/- 18 days, respectively). It is concluded that traumatic axonopathy as well as toxic neuropathies can be promoted by PMSF. Moreover, it appears that PMSF promotion involves a target and a mechanism which are present in healthy axons and do not need to be activated by the insult to the axon. PMID- 8344004 TI - Postscript to the symposium on organophosphorus compound induced delayed neuropathy. AB - A short review is presented on the key points in the development of the hypothesis for the initiation of delayed neuropathy by reaction of organophosphorus compounds with neuropathy target esterase (NTE). It is now clear from information derived from experiments showing protection and promotion and from the action of some phosphorothioamidates (which cause delayed neuropathy without aging) that the original NTE hypothesis is not generally applicable and requires modification. A suggestion is made that aging of phosphorylated and phosphonylated NTE is facilitated perhaps by two linked esterases, one being NTE. PMID- 8344005 TI - The esterases: perspectives and problems. AB - Many proteins capable of hydrolysing esters are present in biological material of all kinds (microorganisms, plants, invertebrates and vertebrates). Some serve, as indicated by their substrate specificity and distribution within organisms, a defined biological function. However for most esterases a rather general substrate specificity is found indicating that they may have a broad biological function. Their properties will be briefly reviewed with particular emphasis on inhibitors. The mechanism of hydrolysis of esters by many carboxylesterases (B esterases) is well established largely due to the reaction of OP compounds with their catalytic centre. For others, such as enzymes hydrolysing (i) OP compounds and/or (ii) carboxyl esters which are not inhibited by a time and temperature dependent reaction by OP compounds, reaction mechanisms are still conjecture. The purpose of this presentation is to explore similarities and differences between the esterases and to discuss possible routes for progress in the A-esterase group. PMID- 8344006 TI - Catalytic antibodies hydrolysing organophosphorus esters. AB - Transition state stabilization is considered one means by which enzymes reduce free energy of activation. The transition state of phosphonic acid anhydrides acted on by OPA hydrolase is postulated to be pentacoordinate, which ordains either a square pyramid or a trigonal bipyramid structure. The advent of catalytic monoclonal antibodies has provided a system in which these assumptions can be tested. By immunizing mice with the protein conjugate of a trigonal bipyramid transition state analog, we have produced hybridomas secreting monoclonal antibodies which hydrolyze phosphonates. To date, activity has been shown toward pinacolyl methylphosphonofluoridic acid (soman). Preliminary results suggest that the antibody is an IgG2a with kappa light chain character. Our results support the trigonal bipyramidal transition state for this group of enzymes. PMID- 8344007 TI - Paraganglioma of the cauda equina: a case report and review of the literature. AB - This case report describes a paraganglioma of the cauda equina in a 57-year-old man. The clinical and pathological features of the 70 cases reported to date are reviewed. The importance of total surgical removal is stressed. PMID- 8344008 TI - Delay in diagnosis of X-linked adrenoleukodystrophy. AB - In 16 consecutive patients with clinically suspected and biochemically proven X linked adrenoleukodystrophy (X-ALD), total delay (interval between onset of symptoms and diagnosis) and specialist delay (interval between referral to a specialist and diagnosis) were determined. All patients previously were unaware of the existence of X-ALD in their families. From the time of onset of symptoms attributable to this disease until diagnosis, mean total delay was 9.9 (range 1 33) years and mean specialist delay was 8.4 (range 0-33) years. Three patients who presented with adrenocortical insufficiency had mean total and specialist delays of 17.3 (range 9-33) years. Five patients with an initial diagnosis of multiple sclerosis had mean total and specialist delays of 12.8 (range 5-25) and 11.2 (range 1-23) years, respectively. In 12 patients with adrenomyeloneuropathy- the second most frequent phenotype of X-ALD--mean total delay was 11.0 (range 2 33) years and mean specialist delay 9.1 (range 0-33) years. Since 1981 X-ALD can be reliably diagnosed on the basis of elevated levels of very long chain fatty acids in plasma and/or cultured fibroblasts. The delays therefore must have been due to the unfamiliarity with the clinical manifestations and diagnostic possibilities of this disease. Once X-ALD is diagnosed, dietary treatment and/or bone marrow transplantation may be considered. Genetic counseling should be performed, and screening of other family members is essential for the early identification of affected relatives. PMID- 8344009 TI - Somatosensory evoked potentials after iohexol myelography. AB - Tibial nerve and S1 dermatome somatosensory evoked potentials (SSEPs) were recorded before and after iohexol lumbar myelography in order to evaluate possible neurotoxic effects of this contrast medium. No significant change in SSEP latencies nor amplitudes was noted after iohexol myelography, supporting the low neurotoxic profile of this contrast agent. Results were compared to those of a control group of patients before and after lumbar puncture (LP), without injection of contrast agent. In this group also no significant change in SSEP components was found, indicating that a preceding LP does not affect this electrophysiological examination. PMID- 8344010 TI - Hereditary spastic paraparesis. Clinical and genetic data from a large Dutch family. AB - A large Dutch family is presented with pure hereditary spastic paraparesis. Pedigree analysis indicates autosomal dominant inheritance with complete penetrance and possibly anticipation in successive generations. These observations may have implications for genetic studies. Linkage studies in this family have excluded more than 40% of the autosomal genome. PMID- 8344011 TI - Amnesic syndrome caused by neurosarcoidosis. AB - A 20-year-old woman presented with subacute amnesia, which turned out to have been caused by neurosarcoidosis. The patient showed several remarkable features: isolated bilateral temporal hydrocephalus, caused by ventriculitis/arachnoiditis; spinal arachnoiditis as demonstrated by myelography, which was not noticed on MR scan. Diagnostic difficulties that are sometimes encountered when neurosarcoidosis is suspected (particularly the differentiation from neurotuberculosis if insufficient evidence of systemic sarcoidosis is found) are discussed. PMID- 8344012 TI - Coexistence of Parkinson's disease and myasthenia gravis: a case report. AB - This is a report on a 62-year-old Chinese woman with Parkinson's disease (PD) for 8 years who developed myasthenia gravis (MG) in the last year. In this case, there was no adverse effect of trihexyphenidyl on MG, whereas pyridostigmine worsened the PD. PMID- 8344013 TI - Hemiparkinsonism in a patient with primary Sjogren's syndrome. A case report and a review of the literature. AB - A 55-year-old woman presented with hemiparkinsonism on the left side. Clinical features suggested primary Sjogren's syndrome. Eye tests and a salivary gland biopsy confirmed this diagnosis. Magnetic resonance imaging of the brain showed distinct linear lesions of increased intensity on the T2-weighted images in the right striatum and globus pallidum. Treatment with prednisone and azathioprine did not give any improvement of the neurological symptoms. To date, hemiparkinsonism in association with primary Sjogren's syndrome has not been reported. PMID- 8344014 TI - Central nervous system lymphoma presenting with ataxic hemiparesis: a case report. AB - An 81-year-old man with central nervous system (CNS) lymphoma presenting with acute, progressive ataxic hemiparesis. Computed tomography and magnetic resonance imaging localized the lesion extending from the right internal capsule to the ventrolateral aspect of rostral midbrain tegmentum. A stereotactical biopsy yielded a microscopic diagnosis of medium-sized diffuse B-cell lymphoma. Although the most frequent cause of the syndrome of ataxic hemiparesis is a lacunar type of cerebral infarction, this article emphasizes that CNS lymphoma can produce the syndrome. PMID- 8344015 TI - Hydrocephalus due to bilateral obstruction of the foramen of Monro: a 'possible' late complication of mumps encephalitis. PMID- 8344016 TI - Calcification of basal ganglia associated with pontine calcification in four cases: a radiologic and genetic study. AB - We describe 4 brothers with calcification of basal ganglia, pons and dentate nuclei. An abnormal iron metabolism was found in one case. The radiological, pathogenetic and genetic aspects of this disease are discussed. PMID- 8344017 TI - A case of pontine lacunar infarction with ulcerative colitis. AB - We present the case of a young man who experienced a sudden onset of pure motor hemiplegia in association with ulcerative colitis. Based on a review of earlier reports, ulcerative colitis was suspected to be the background disease leading to cerebral infarction. A cerebral infarction of the lacunar type in the right ventromedial aspect of the upper pons was seen on magnetic resonance images. These images detected small lesions in the brain stem, and were used to follow-up their transitions. PMID- 8344018 TI - Reliability of the diagnosis of a first seizure. PMID- 8344019 TI - Neuro-imaging in the diagnosis of Alzheimer's disease. II. Positron and single photon emission tomography. PMID- 8344020 TI - Hereditary motor and sensory neuropathies. Present status of types I, II and III. PMID- 8344021 TI - The role of thallium scintigraphy in excluding malignancy in bone. AB - Scintigraphy with thallium-201 was performed on 22 patients in whom a solitary abnormality in bone was suspected of being malignant. In three patients, an additional lesion was subsequently identified. Preferential TI-201 uptake was found in 7 of 8 malignant lesions, but was absent in 16 of 17 abnormalities that proved to be benign. The use of TI-201 scanning is considered to offer high negative predictive value in the assessment of possible malignant change in bone. PMID- 8344022 TI - Infarctions of the ilia in young patients with sickle hemoglobinopathies. AB - Infarctions of the long bones in sickle cell anemia and some of its variant hemoglobinopathies are well known. Photopenia representing areas of acute infarctions of the ilia in two young children are presented as unusual presentations of bone ischemia. PMID- 8344023 TI - Parathyroid adenoma demonstrated with TI-201 SPECT. AB - A case of parathyroid adenoma with suppressed Tc-99m pertechnetate uptake of the thyroid due to L-thyroxine replacement therapy for hypothyroidism is reported. This case demonstrates successful localization of a parathyroid adenoma in the retrothyroid space using TI-201 SPECT. When the thyroid uptake of Tc-99m pertechnetate is reduced for whatever reason, a planar TI-201 followed by SPECT may be more helpful than TI-201/Tc-99m subtraction scintigraphy. PMID- 8344024 TI - DEXA bone densitometry measurements in adults with X-linked hypophosphatemia. AB - Bone mineral densities in adults with X-linked hypophosphatemia are variable, and while most are reportedly normal some can be very high. Eighteen patients with adult X-linked hypophosphatemia underwent bone mineral determinations of the lumbar spine and femoral neck with dual energy x-ray absorptiometry (DEXA). Most of them were on various treatment regimens. Ten of 18 patients (55%) had spinal bone mineral densities that were greater than two standard deviations above the age-matched mean, and 3 of 11 patients (27%) had bone mineral densities of the femoral neck in excess of two standard deviations. Eight patients (median age 41.5 years) were followed serially for 24 to 42 months, and they exhibited a spinal bone loss of 0.019 gm/cm2/year. PMID- 8344025 TI - Bone scan appearances of a metastasizing aggressive osteoblastoma. A case report. PMID- 8344026 TI - Detection of focal inflammation with Tc-99m HMPAO labeled leukocytes in children. AB - To evaluate the applicability of Tc-99m HMPAO leukocyte scintigraphy in the assessment of focal infections in children, we retrospectively analyzed 26 studies performed between 1988 and 1992. All patients (n = 25, age range 1 month 15 years) were severely ill and suspected to have invasive bacterial infection. In each case, whole body scintigraphy was performed 2-4 hours after injection of autologous labeled leukocytes. There were 8 true positive and 14 true negative cases; specificity was 88% and sensitivity 80%. The two false negative findings were observed in patients on immunosuppressive therapy; both had fungal infections. In one case, atypical non-specific bowel accumulation of the tracer was falsely interpreted as an abscess. The other false positive finding was hip accumulation in a patient who later turned out to have Mucha-Haberman disease; transient synovitis may explain the finding. Of the eight true positive cases, six had an invasive infection focus and two had an aseptic inflammatory process. Tc-99m HMPAO leukocyte scintigraphy is a valuable method in the assessment of focal inflammation in children, including infants. PMID- 8344027 TI - Normal brain F-18 FDG-PET and MRI anatomy. AB - Image registration techniques will become increasingly important in correlative multimodality imaging. In the case of PET, a structural imaging study can be invaluable in correlating structure metabolism relationships. A registered brain atlas of PET and MRI has been developed by the authors that allows clinicians, residents, fellows, and others to refer to a structural abnormality on MRI or metabolic abnormality on PET and correlate it neuro-anatomically. PMID- 8344028 TI - The attenuation effect in brain SPECT. AB - False perfusion defects simulating Alzheimer's disease can be attributed to skull thickness and head holders of a SPECT scan table. Brain phantom SPECT was performed using a different type of head holder in order to evaluate the effect of attenuation due to head holders and skull thickness on brain SPECT. Skull thickness was measured in 10 normal or non-Alzheimer's patients and 10 patients with suspected Alzheimer's disease. Visual and quantitative analysis of regional perfusion showed a 19% count loss due to attenuation by commercially available head holders and average skull thickness, less than 18% count difference between frontal-temporal and parietal-occipital skull in non-Alzheimer's disease patients, and more than 22% count difference observed in suspected Alzheimer's patients. PMID- 8344029 TI - Planar and SPECT imaging with technetium-99m labeled antigranulocyte antibodies in bone and soft tissue infection. AB - Scintigraphy with technetium-99m labeled antigranulocyte antibodies including planar and SPECT imaging demonstrated areas of inflammation in bone and soft tissue of the thigh of a 38-year-old man who had a fracture of the femur 20 years earlier. The clinical potential of this imaging modality in the diagnostic assessment of inflammatory diseases is discussed. PMID- 8344030 TI - Grossly abnormal liver-spleen scan in a patient with veno-occlusive disease of the liver that normalized completely on follow-up. AB - A case of veno-occlusive disease of the liver of unknown etiology is reported. In the case, the gross abnormality of liver parenchyma, ascites, and colloid shift to spleen, bones, and lungs found on a Tc-99m SC liver-spleen scan, and confirmed on liver biopsy, resolved completely on follow-up. Histologic correlation and a brief review of the literature are presented. PMID- 8344031 TI - Fibrosing mediastinitis causing nonvisualization of one lung on pulmonary scintigraphy. AB - An interesting case of fibrosing mediastinitis, which is a rare cause of total nonvisualization of one lung on pulmonary scintigraphy, is presented. Scintigraphy with Tc-99m MAA showed a severe deficit of perfusion in the right lung, with normal perfusion of the left lung. Ventilation images were normal. CT and MRI each demonstrated the mediastinal nodal enlargement and MRI demonstrated the "flow void" signal phenomenon in the right pulmonary artery indicating its patency. Confirmation of actual patency without pulmonary artery emboli and with poor venous opacification was documented with angiography. Multiple complementary imaging modalities were helpful in correctly diagnosing fibrosing mediastinitis from an extensive list of differential possibilities for unilateral non visualization of the lung on perfusion scanning. PMID- 8344032 TI - Thyroid scintigraphy during antithyroid treatment for autonomous nodules as a means of imaging extranodular tissue. AB - The scintigraphic appearance of the thyroid gland after a course of methimazole treatment was studied in 22 patients with autonomous hot nodules. After 2-3 months of treatment the extranodular tissue was reactivated in almost every patient. This treatment constitutes an endogenous TSH stimulation test and may be used clinically in selected cases. PMID- 8344034 TI - Stage II reflex sympathetic dystrophy syndrome with unexpected bone changes due to the use of walking crutches. PMID- 8344033 TI - Antibiotic associated colitis. A cause of absent marrow activity on In-111 leukocyte imaging. PMID- 8344035 TI - Differential excretion of a transplanted kidney with dual vascular supply. PMID- 8344036 TI - Bilateral photon deficient area along lateral abdominal wall in a Tc-99m DTPA renogram. A sign of massive ascites. AB - A patient with congestive heart failure and hepatic and renal dysfunction underwent Tc-99m DTPA renal scintigraphic studies in which persistent cardiac blood pool activity, hepatic arterialization, and a longitudinal photon deficient area in each side of the abdominal wall were observed. The increase in hepatic artery inflow was believed to be due to a decrease in portal inflow of the liver. The elevation of portal pressure secondary to heart failure is attributable to the decrease in portal inflow of the liver; this phenomenon could account for the hepatic arterialization. Progressive renal dysfunction with high body background resulted in demonstrable ascites as photon deficient areas. Scintigraphic findings of hepatic arterialization plus an abdominal photon deficient area reflect severe heart failure and renal dysfunction. PMID- 8344038 TI - Psoas abscess demonstrated with SPECT and CT. PMID- 8344037 TI - Acute lobar nephronia secondary to infection with nocardia asteroides. PMID- 8344039 TI - Tc-99m HMDP accumulation in an alveolar soft part sarcoma. PMID- 8344040 TI - Three-dimensional surface display with I-123 IMP in amyotrophic lateral sclerosis. PMID- 8344041 TI - Incidental visualization of pituitary tumors during brain SPECT imaging with Tc 99m HMPAO. PMID- 8344042 TI - Thoracic organ transplantation in children. The state of heart, heart-lung, and lung transplantation. AB - Heart, heart-lung, and lung transplantation have become accepted modalities for treatment in children with serious cardiopulmonary disease. Although early deaths secondary to infection and/or acute rejection have been reduced dramatically, there is still an early mortality related to cardiac complications and a late mortality related to rejection and infection. The management of hypoplastic left heart syndrome remains a special problem and is outlined in the review. There is much less experience in the newer modalities of heart-lung and lung transplantation in children and the results of these operative procedures are similar to what was seen in heart transplantation some 10 years ago. Ongoing and significant improvement continues, however, in all forms of transplantation dealing with the lung. PMID- 8344043 TI - Overall function in rural childhood cancer survivors. The role of social competence and emotional health. AB - This study compared the functioning of 20 rural cancer survivors, aged 6 to 16 years, with that of 40 age- and gender-matched school peers. Social competence and emotional health were evaluated, along with academic performance and physical limitations. Eight measures were used: the teacher and parent Child Behavior Check Lists, the Health Resources Inventory, the Vineland Revised Scale of Social Maturity, the Piers-Harris Child's Self-Concept Scale, the Parcel and Meyers' Health Locus of Control, the Moos' Family Environment Scale, and the Functional Status II(r). Cancer survivors and controls had similar attitudes about self esteem, family conflicts, physical functioning, social skills, independence, and sense of control over health. Both parents and teachers noted poorer social competence among the cancer survivors than among controls, but parents of survivors reported more behavior problems, whereas teachers stressed poorer school performance. Routine screening for emotional health, social competence, and academic performance should be part of the follow-up care of pediatric cancer survivors. PMID- 8344044 TI - Correlating changes in body temperature with infectious outcome in febrile children who receive acetaminophen. AB - We reviewed the body-temperature patterns of 140 children ages 2 to 24 months who had fever > or = 39.0 degrees C, received acetaminophen 10 to 15 mg/kg, and had their temperatures remeasured 60 to 90 min later. The children comprised three groups: 22 had bacterial meningitis; 59, isolated bacteremia; and 59, nonbacterial febrile illness. Percentages of patients who became afebrile (temperature < 38.0 degrees C) after receiving acetaminophen were not significantly different among the three groups. Differences in mean temperature decrease after antipyretic was given were significant within each group but not between groups. An inverse relation (P < .004) between patient age and magnitude of temperature was revealed by the following formula: degrees C of defervescence = 1.66 - (0.028 x patient age in months). Thus, highly febrile young children with and without invasive bacterial infections who receive a therapeutic dose of acetaminophen experience a significant temperature drop after 60 to 90 min but do not commonly defervesce to an afebrile state. The degree of defervescence is age dependent and does not distinguish between infectious outcomes. PMID- 8344045 TI - The accuracy of infrared auditory canal thermometry in infants and children. PMID- 8344046 TI - Respiratory syncytial virus as a cause of fever and petechiae in infants. PMID- 8344048 TI - Development of pneumococcal meningitis during ceftriaxone therapy. PMID- 8344047 TI - Thyroid involvement in children with familial Mediterranean fever. PMID- 8344049 TI - Unilateral pulmonary edema in children. PMID- 8344050 TI - Causes of recurrent abdominal pain. PMID- 8344051 TI - Cerebrospinal fluid pleocytosis in children with pneumonia but lacking evidence of meningitis. AB - Headache, nuchal rigidity, positive Kernig's sign, and even convulsions may be observed during severe bacterial infections such as pneumonia, pyelonephritis, typhoid fever, and bacillary dysentery. In such cases, meningitis can be excluded only by documentation of normal cerebrospinal fluid (CSF). The authors describe four children with lobar pneumonia in whom the clinical signs of meningeal irritation were associated with a mild increase in the white blood cell count in the CSF (pleocytosis) although there was no other evidence of meningeal infection. PMID- 8344052 TI - Pediatric Miller Fisher syndrome requiring intubation: a case report. AB - In 1956, C. Miller Fisher described a clinical syndrome of ophthalmoplegia, ataxia, and areflexia. This syndrome, which now bears his name, shares certain features with the Guillain-Barre syndrome (GBS) and generally follows a benign, restricted clinical course, especially in the pediatric population. The authors report a pediatric case of Miller Fisher syndrome (MFS) who subsequently required intubation and mechanical ventilation. PMID- 8344053 TI - Extreme hyperlipidemia in type I diabetes mellitus. PMID- 8344054 TI - The patient care evaluation system: patients' perception of anesthetic care. AB - Our department's Patient Care Evaluation Survey was developed to measure the patients' perception of the care they received by our anesthesia caregivers (attending physicians, residents, and certified registered nurse anesthetists [CRNAs]), and identify those areas of patient contact which might require improvement in the delivery of anesthesia. The survey instrument (a personal letter sent by the chairman), is mailed to randomly selected patients two weeks following discharge from the hospital or ambulatory surgery center. Patients rated the anesthesia care they received from one (poor) to 10 (excellent) in three areas: the preoperative visit, the postoperative visit, and overall satisfaction. From October 1986 to October 1991, a total of 2,374 (n = 2,374) questionnaires representing a random sample of 99,964 anesthetics, were sent to patients. Fifty-four percent or 1,291/2,374 patients returned the survey. A high degree of patient satisfaction is seen for all categories: the preoperative visit, (mean score of 9.17 +/- 1.6); the postoperative visit (8.33 +/- 2.7); and overall satisfaction (9.15 +/- 1.7). Of the responses returned, 0.9% of the patients surveyed rated their interaction with the department as unsatisfactory in all three areas; 2.6% in two areas; 10.8% in at least one area. The Patient Care Evaluation system has served as an important means of feedback for medical, educational, and administrative goals of the department. PMID- 8344055 TI - Introducing physicians to case management in psychiatry. AB - All physicians sooner or later find themselves in contact with a case manager whose job is to help the noninstitutionalized psychiatric patient who is chronically ill. This paper is an attempt to orient the physician about this phase of treatment which started not many years ago. The article gives a short history of the development of case management and demonstrates the various steps the case manager takes in working with a patient. These are, assessment of the problems, plans to meet the problems, linkage with agencies, monitoring the progress, advocacy, and evaluation. These activities may bring about improvement in the kind of patient frequently considered hopeless. PMID- 8344056 TI - Social correlates of malnutrition among Filipino street children. AB - This study has sought to identify subgroups of street children at high risk for nutritional deficiency in metropolitan Manila in the Philippines. A sample of 150 street children ages six through 18 were weighed, measured, and interviewed to establish nutritional parameters and to explore the interrelationships of nutritional status with social conditions. Two variables showed the highest association with low weight for age: children using drugs and children not in school. These variables should be seen as indicative of a range of variation among Filipino street children, in whom those on drugs and not in school represent the sector at greatest risk and one to which nutritional programs should be targeted. PMID- 8344057 TI - The Connecticut State Medical Society and the Connecticut Medical Insurance Company. PMID- 8344058 TI - A doctor's child is born. PMID- 8344059 TI - The international control of disease after the war. 1943. PMID- 8344060 TI - Reexamining liability for acts that lead to death. PMID- 8344061 TI - I swear by Apollo physician. PMID- 8344062 TI - Medical hydrology. PMID- 8344063 TI - Ethacrynic acid: outflow effects and toxicity in human trabecular meshwork in perfusion organ culture. AB - The effect of ethacrynic acid, a potential outflow agent for the treatment of glaucoma, was studied in a series of 25 pairs of human eyes in perfusion organ culture. Concentrations varied from 0.01 mM to 2.4 mM and were used in single or repetitive doses. Intraocular pressure was continuously recorded for up to two weeks after exposure. Eyes were then fixed and the meshwork examined histologically. Ethacrynic acid in single doses of 0.05 mM, 0.3 mM, and 0.6 mM increased facility of outflow at least 40% when compared with fellow control eyes. The duration of effect was approximately 18 hours, during which time the intraocular pressure gradually returned to baseline. Histologic examination revealed dose related effects on the trabecular cells, ranging from clumping of nuclear chromatin in some eyes to cellular swelling, disruption of cytoplasmic membranes, and cell necrosis in other eyes at concentrations of 0.1 mM and higher. No recovery or reversal of these changes was noted with time, even two weeks after a single exposure to the drug. Although ethacrynic acid is effective in temporarily lowering intraocular pressure in the human eye, a low therapeutic index may limit its clinical usefulness. PMID- 8344064 TI - A comparison of 5-fluorouridine and 5-fluorouracil in an experimental model for the treatment of vitreoretinal scarring. AB - 5-Fluorouridine (5-FUR), a ribonucleotide metabolite of 5-Fluorouracil (5-FU), is a more potent inhibitor of cellular proliferation and cell-mediated contraction in vitro than 5-FU. We compared the efficacy of these two drugs in a cell injection model of proliferative vitreoretinopathy using New Zealand albino rabbits. Forty-five eyes were divided into three groups and injected intravitreally with homologous fibroblasts. Eyes were examined at the time of injection and 7, 14, 21 and 28 days thereafter. By day 28, 70.5% (12 of 17) of 5 FUR treated eyes demonstrated no appreciable proliferative or tractional activity compared with 41.7% (5 of 12) of 5-FU treated eyes and 10% (1 of 10) of control eyes (p < 0.006). Medullary ray puckers developed in 29.4% (5 of 17) and 25% (3 of 12) of 5-FUR and 5-FU treated eyes respectively. No 5-FUR treated eye developed extensive tractional or combined tractional and rhegmatogenous retinal detachment compared with 33.3% (4 of 12) of 5-FU treated eyes and 80% (8 of 10) of control eyes (p < 0.001). These results suggest that 5-Fluorouridine may be more effective than 5-FU for the treatment of vitreoretinal scarring. PMID- 8344065 TI - Protein kinase C activity and its relationship to myo-inositol uptake during hyperglycemic conditions in cultured bovine lens epithelial cells. AB - Incubation of cultured bovine lens epithelial cells (BLECs) in minimal essential medium (MEM) containing 40 mM galactose for 20 hr results in an attenuation of 3H myo-inositol (3H-MI) concentrating ability. Decreased MI uptake could negatively impact on normal phosphoinositide turnover and diacylglycerol production, and presumably, protein kinase C (PKC) activation. The present report examines the relationship between PKC activity, myo-inositol transport and hyperglycemic conditions. PKC activities in the cytosol and particulate fractions of bovine lens epithelial cells in culture were quantitated using a mixed micelle assay following DEAE-cellulose (DE52) and Sephadex G-25 chromatography. Protein kinase C activity was assessed as Ca2+ and phospholipid-dependent Ac-myelin basic protein substrate peptide phosphorylation and confirmed using a PKC pseudosubstrate inhibitor peptide (PKC 19-36). Total PKC activity was similar in galactose-incubated cells (871 +/- 64 pmol/mg total protein/min) and control cells (881 +/- 8 pmol/mg total protein/min) after 20 hr. In unstimulated cells, approximately 90% of the total cellular PKC activity was recovered in the cytosolic fraction. Enzyme translocation was induced with the tumor promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), resulting in a 6-fold increase in membrane-associated PKC activity. A similar PMA-induced translocation was observed in BLECs incubated with 40 mM galactose MEM-maintained cells briefly treated with PMA or the non-phorbol PKC activators, SC-10 and mezerein, displayed a rate of 3H-MI uptake similar to the untreated control cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344066 TI - DNA single strand breaks in human lens epithelial cells from patients with cataract. AB - In recent years, there has been renewed interest in the association between DNA damage to the lens epithelium and the development of lens opacities. Although a number of in vitro studies have indicated that lens epithelial cells are susceptible to a variety of DNA damaging insults and that these cells possess the capacity to repair such damage, no previous studies have directly addressed whether DNA damage is associated with human cataract in vivo. Utilizing samples of lens epithelial cells obtained from patients undergoing cataract surgery, the percentage of cells containing DNA single strand breaks was directly determined by the single-cell gel assay (SGA) method. Non-cataractous human Eye Bank lenses of similar ages to the cataractous samples and calf lenses were used as controls. In approximately 50% of the cataractous samples analyzed, the proportion of cells containing DNA single strand breaks was significantly higher than in control lenses. No relationship between age and DNA damage was noted. These findings are consistent with the hypothesis that in some human patients with cataract, DNA damage in the lens epithelial cell population may be related to the development of lens fiber cell opacity. PMID- 8344067 TI - Distribution and activity of glutathione-S-transferase in normal human lenses and in cataractous human epithelia. AB - The distribution of glutathione-S-transferase (GST) activity was determined in frozen normal human lenses. The highest activity of GST was found in the peripheral and equatorial regions, whereas the lowest activity was found in the nucleus. Western blot showed that both mu and pi isoenzymes of GST were present in human lenses. This result is similar to that found in rat lenses. In addition, GST activity was analyzed in 50 lens epithelia which were obtained during cataract surgery. Twenty-seven lens epithelia showed no activity. Statistically significant association was found between cortical and mixed cortical--nuclear cataract and loss of GST activity. No association was found between pure nuclear cataract and loss of epithelial GST activity. PMID- 8344068 TI - Developmental changes in carbachol-stimulated inositolphosphate release in pigmented rat retina. AB - Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) following in vitro incorporation of [3H]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM) stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, reaching adult levels by PND 20. Retinal weight and protein per retina also increased (four fold) from day 5 to adult; however, the in vitro incorporation of [3H]myo-inositol into phosphoinositides (calculated as per mg protein) did not change during development. Thus, in animals prior to eye opening, a much higher proportion of phosphoinositides appears to be hydrolyzed upon muscarinic receptor stimulation. During retinal development a change in sensitivity to the agonist sensitive pool(s) of phosphoinositides may occur and/or there may be alterations in the efficacy of receptor coupling to the second messenger system resulting in the disassociation observed between the drastic increase in receptor number and the apparent decrease in receptor-stimulated release of IP. PMID- 8344070 TI - Prednisolone acetate or prednisolone phosphate concurrently administered with ciprofloxacin for the therapy of experimental Pseudomonas aeruginosa keratitis. AB - This study was conducted to determine the therapeutic efficacy of 3.0 mg/ml ciprofloxacin administered concurrently with one of two salts of prednisolone for the treatment of experimental pseudomonal keratitis. Rabbit corneas were injected intrastromally with Pseudomonas aeruginosa ATCC strain 27853. Sixteen hr after injection, rabbits were randomly divided into four treatment groups (3 rabbits, 6 eyes per group): 1) ciprofloxacin plus prednisolone acetate; 2) ciprofloxacin plus prednisolone phosphate; 3) ciprofloxacin only; 4) untreated. Signs of inflammation were graded in a masked fashion by slit lamp examination (SLE) and by estimating polymorphonuclear leukocyte (PMN) numbers in corneas 27 hr after injection. SLE scores and PMN numbers were significantly lower (P < 0.02) in eyes receiving either salt of prednisolone plus ciprofloxacin compared to the untreated controls. In contrast, SLE scores and PMN numbers were not significantly different in eyes treated with ciprofloxacin alone, compared to untreated controls (P > 0.13). No viable bacteria were recovered from any eye treated with ciprofloxacin (groups 1, 2, and 3). Ciprofloxacin concentrations in the aqueous humor of eyes in groups 1, 2, and 3 were greater than 15-fold higher than the MIC for P. aeruginosa 27853. These results suggest that either salt of prednisolone, when combined with ciprofloxacin, reduces ocular inflammation without affecting the antimicrobial efficacy of the antibiotic. PMID- 8344069 TI - Pseudomonas aeruginosa keratitis in leukopenic rabbits. AB - To study the role of the host inflammatory response in Pseudomonas aeruginosa keratitis, rabbits were made leukopenic with intravenous injections of cyclophosphamide and dexamethasone. Twenty-four hr later, keratitis was initiated in all rabbits with an intrastromal injection of 1,000 log phase P. aeruginosa strain 27853. Slit lamp examination of eyes showed that leukopenic rabbits had significantly less (P < 0.0001) ocular pathology at 16, 22, and 27 hr postinfection. The number of viable bacteria recovered from corneas of leukopenic rabbits was the same as the number recovered from nonleukopenic rabbits (P = 0.95). These results suggest that the host inflammatory response significantly contributes to the overall ocular pathology associated with P. aeruginosa keratitis, but does not influence the survival of the infecting organism in the cornea at the height of the infection. PMID- 8344071 TI - External humeral condylar fracture in children. A long-term review of 30 cases operated. AB - Follow-up ranging from 2 to 14 years (mean 6 years) was obtained for 30 fractures of the external humeral condyle in children aged from 2 to 11 years; the patients had been submitted to reduction-osteosynthesis. Twelve patients were at the end of the growth period when followed-up. All of the patients were classified as Lagrange and Rigault grades II and III. Synthesis always involved two or three Kirschner wires bent under the skin. There were 24 perfect results and 6 good ones. Valgus equal to less than 10 degrees was present in 2 cases. Deficit in flexion-extension, present in 4 cases, did not exceed 20 degrees overall. Another case showed "fish-tail" radiographic deformity (due to epiphysiodesis) which did not interfere with function. Despite the potential danger of the lesion, the authors believe that careful surgical treatment provides very satisfactory results. PMID- 8344072 TI - Anesthesia and perioperative treatment in large resections of the pelvic girdle. AB - The authors examine 24 patients submitted to resection of the pelvic girdle in neoplastic pathology, illustrating the perioperative anesthesiologic procedures used. Sudden variations in blood and plasma volume and increasing hypothermia constitute the main problems. The prevention of hypothermia and continuous invasive monitoring of hemodynamic parameters and of oxygen saturation in mixed venous blood (SvO2) are of primary importance. PMID- 8344073 TI - Osteoid osteoma of the carpal scaphoid in the adult: a clinical case. AB - The authors present one case of osteoid osteoma of the carpal scaphoid, emphasizing the clinical rareness of the disease. Methods of diagnosis used and surgical treatment performed are described. PMID- 8344074 TI - Isolated dislocation of the pisiform. A case report. AB - The clinical case of an 81-year-old woman with an isolated pisiform dislocation is reported. This is an extremely rare lesion due to the sturdiness of the ligamentous complex which stabilizes the pisiform to the carpus; when it does occur closed reduction is impossible because of the action of the FCU tendon. In symptomatic cases the best therapeutic procedure consists in the surgical removal of the bone, resulting in complete recovery without consequence. PMID- 8344075 TI - Two cases of solitary subcutaneous angioleiomyoma. PMID- 8344076 TI - Quiz. McLaughlin fracture of the right humeral head with posterior dislocation of the shoulder. PMID- 8344077 TI - Anterior surgery of the upper part of the cervical spine by prevascular extraoral approach. AB - Anterior surgery of the upper part of the cervical spine, that is, proximal to C3, may be performed by transoral approach, possibly enlarged by glossomandibulotomy, by a retrovascular extraoral approach, or by a prevascular extraoral approach. The authors describe the surgical method of prevascular extraoral approach that allowed them to effectively treat osteoma localized at C2 and C3, post-laminectomy instability at C3 and C4, solitary metastasis at C3. As compared to transoral surgery the prevascular extraoral approach has the advantage of avoiding the risk of infection from germs in the oral cavity and of allowing for easier postoperative management, avoiding tracheotomy and/or prolonged dysphagia. As compared to a retrovascular approach the prevascular approach obtains a truly anterior exposure instead of an anterolateral one. Prevascular extraoral approach should thus be used whenever possible. Transoral surgery is indicated for decompression, of the brainstem and a bilateral retrovascular approach may be used to perform anterolateral fusion at C1-C2. PMID- 8344078 TI - Microsurgery in the treatment of crural and sciatic pain due to disc and bone compression: considerations on the first 100 cases. AB - The authors present the results they obtained in the first 100 operations performed between January 1989 and November 1990 for the treatment of lumbar sciatic pain related to disc and/or bone compression: microsurgery according to the Caspar method was used. A total of 113 spaces were submitted to surgery; discectomy at two levels was performed in 13 patients. Nerve root compression observed was based on three causes: 1) pure disc hernia (57.5%), 2) pure lateral stenosis (15.9%), 3) combined pathology (hernia+stenosis) (25.6%). In one of the cases the pathology remained unknown. At an average two-year follow-up there were 94 excellent or good results, 2 fair results, and 4 poor results. Complications included dural lacerations in 3 cases, with no sequelae. Eight patients were submitted to further surgery for recurrence of symptoms; the final results after reintervention were excellent in 7 cases, and fair in 1. The authors emphasize the advantages to using microsurgery as compared to macrosurgery, and stress a frequent finding of pure lateral stenosis or associated with disc pathology (47 out of 113 levels operated, equal to 41%), as well as the reliability of CT scan when dealing with disc pathology (97% positive diagnosis) but its unreliability when diagnosis is lateral stenosis (19 out of 47, equal to 40%). PMID- 8344079 TI - The use of massive bone allografts for intercalary reconstruction and arthrodeses after tumor resection. A multicentric European study. AB - A multicentric study was conducted by the European Musculoskeletal Oncology Society on 113 cases of resection for tumors of the major long bones and reconstruction with massive allografts, as intercalary diaphyseal or for arthrodesis. The follow-up was at least 12 months. There was a 14% incidence of infection, with a higher frequency (18.5%) in intercalary grafts as compared to arthrodeses (7%). Fracture of the graft occurred in 15.5% of the cases with a prevalence in the humerus (28.5%) as compared to the tibia (21.4%) and femur (14.7%). Fracture constantly occurred after osteosynthesis with screws, in 16% of the cases after osteosynthesis with a plate, and in 12.5% of the cases after osteosynthesis with an intramedullary nail. It was observed in 32% of the grafts preserved at -30 degrees, in 17% of those irradiated, and in 7% and 7.6% of those preserved at -180 degrees and -80 degrees, respectively. Delayed union and non union was observed in 57% of the cases: 63% in intercalary grafts, 48% in arthrodeses. Final results after treatment of complications were excellent and good in 63% of the entire series. The results should, however, be evaluated after 3 years, as during this period of time important transformation phenomena of the graft occur. Complications are observed in 75% of the cases, but they may be reduced if planning is correct and surgery is accurate. Each complication may be dealt with and resolved without high risks for preservation of the limb. PMID- 8344081 TI - [Pregnancy-induced hypertension and serum endothelin]. PMID- 8344080 TI - Gastrocnemius flaps in the surgical treatment of sarcomas of the knee. AB - The authors discuss their experience with the pediculated gastrocnemius flap used in the oncological surgery of the knee, in 27 patients. Three groups of patients are evaluated: in one group the method was used in patients affected with bone sarcoma and associated with reconstruction of the resected bone segment; in another group the method was used after infection had occurred as a result of reconstructive surgery; in the third group the method was used at the same time as excision of sarcomas of the soft tissues. The gastrocnemius flap may be used to cover sufficiently wide areas of loss of skin and muscular substance around the knee, and may be effectively used to cover metallic prostheses or composite reconstructive implants (bone-cement-metal). We recommend using the covering technique at the same time as resection and reconstruction are performed in order to avoid the risk of infection, and thus reduce any changes in chemotherapy protocols that postoperative infection would require in these patients. The use of the gastrocnemius flap associated with excision of sarcomas of the soft tissues must be reserved for selected cases. The high incidence of local recurrence after such excisions indicates that either wider excisions using distant free flaps or the association of radiotherapy should be considered. PMID- 8344082 TI - [Neonatal effects of uterine incision-to-delivery interval during elective cesarean section under epidural anesthesia]. AB - The relationships between uterine incision to delivery interval (U-DI) and neonatal umbilical blood acid-base status and Apgar scores at 1-minute were studied in 130 healthy parturients undergoing elective cesarean section under epidural anesthesia. U-DI was correlated with umbilical venous (UV) and umbilical arterial (UA) pH, PCO2 and PO2, and was also correlated with 1-minute Apgar scores. U-DI of more than 150 sec was associated with significantly higher UVPCO2, UAPCO2, lower UVpH, UApH, UVPO2, and UAPO2. The only two newborns with low 1-minute Apgar scores (6 and 3) in the present study both had prolonged U-DI (> 150 sec) and inhaled amniotic fluid just before the delivery. It is concluded that U-DI of more than 150 sec has considerable influence on the neonatal status. PMID- 8344083 TI - [Follow-up study on physical and mental development in small-for-gestational age infants]. AB - A follow-up study on physical and mental development was carried out in 35 small for-gestational-age (SGA) and 35 appropriated-for-gestational age (AGA) infants. Excluded for congenital abnormality, intrauterine infection, and neonatal asphyxia SGA and AGA infants were similar in maternal education level, infant sex, illness, and feeding history. The results revealed that the body weight (8.09 +/- 0.73kg), height (69.55 +/- 2.49 cm), head circumference (43.27 +/- 1.67cm), Kaup index (16.17 +/- 1.05), and development quotient (96.37 +/- 5.76, Gesell diagnostic method) level at 40 weeks of age in SGA infants was lower than that in AGA infants (P < 0.001), and the development quotient (DQ) in SGA infants was especially low in language and receptive regions. Cord serum insulin level was significantly correlated with follow-up body weight, height, and DQ level (P < 0.01). This article proposed that infants with intrauterine growth retardation have a physical development delay at 40 weeks of age, and which could be predicted by measuring cord insulin level. PMID- 8344084 TI - [Teratogenic effect of potato glycoalkaloids]. AB - Potato glycoalkaloids were extracted from potato sprout and then analyzed to determine their purity by using TLC and HPLC methods and compare with pure alpha Solanine and alpha-Chaconine of Sigma. The result indicated that the purity of potato glycoalkaloids is 78. 31%, which contains 73.64% alpha-Solanine and 4.67% alpha-Chaconine. The LD50 of mice was 44.721 +/- 5.860 4 mg/kg. In order to determine the toxicity and teratogenicity of potato glycoalkaloids, the effect of potato glycoalkaloids on Kunming pregnant mice were studied. The results showed that: (1) potato glycoalkaloids have teratogenic effects on embryos of mice. It could induce neural tube defects (NTDs), and may be an important teratogen of NTDs. (2) potato glycoalkaloids have embryo toxicity. It could cause the death of embryos and result in absorbed and dead fetuses. (3) potato glycoalkaloids could evidently affect the development of embryos and lead to intrauterine growth retardation (IUGR). An interesting phenomena which just like the clinical manifestation of miscarriage in human being was noticed. If potato glycoalkaloids were given to the pregnant mice on the 5th or 6th day of gestation intraabdominally, vaginal bleeding and abortion would occur, and this has not been reported yet. The animal model of NTDs in this experiments supported our hypothesis that sprouted potato could be a teratogen of NTDs. PMID- 8344086 TI - [Bone metabolism in postmenopausal women and after estrogen treatment]. AB - Changes of bone metabolism in 11 premenopausal women and 109 postmenopausal women were studied. 50 postmenopausal women were randomly divided into 4 groups: 20, 10 and 6 cases were given nylestriol, diethyl stilbestrol and chlorotrianisen respectively, and 14 cases served as control. It was shown that bone mineral content (BMC), and, blood estrogen level in postmenopausal women were significantly lower than those of premenopausal women. Close correlation existed between E1, E2, and BMC. Serum alkaline phosphatase (ALP), bone GLA protein (BGP), urine Ca/Cr and Hpr/Cr were markedly increased in postmenopausal women and declined after 3 months of treatment with nylestriol, diethylstilbestrol or chlorotrianisen. The radial BMC increased by 0.8% with (P > 0.05) nylestriol treatment for one year and decreased by 1.1% (P < 0.05) in the control cases. The present study indicated that postmenopausal estrogen deficiency accelerated bone loss, which was prevented by small substitution doses of estrogen such as nylestriol. PMID- 8344085 TI - [Effect of nylestriol on postmenopausal uterine endometrium]. AB - Curettage was performed in 139 postmenopausal women before as well as 6 months, 12 months and 36 months after Nylestiol (CEE3) therapy, for totally 205 times. It was found that CEE3 could induce endometrial proliferation and uterine breakthrough bleeding, much greater in women using 2 mg of CEE3 than in those using 1 mg. Ciliated cell were present in the proliferative endometrium after CEE3. The endometrial tissues obtained in curettage in women after 12 months' therapy was similar to that of 6 months' therapy. No more endometrium was obtained after 36 months' therapy. Provera were given for women who had proliferative endometrium after 6-12 months' therapy with CEE3 1-2 mg/2w. There were no changes of endometrium. This suggested that further study the interval and dosage of provera should be given with CEE3. PMID- 8344087 TI - [Diagnosis of basal body temperature, serum progesterone and endometrial biopsy for luteal phase defect]. AB - Fourteen infertile women and two women with recurrent abortions were suspected of having luteal phase defect (LPD) by BBT charts. In these patients, the midluteal phase serum progesterone (P) levels were determined together with histological examination by the late luteal endometrial biopsies during the same cycle. The diagnostic criteria for LPD was BBT of luteal phase < or = eleven days, mean P level of 3 blood samples taken on three days during midluteal phase was less than 48 nmol/L (15 ng/ml) and the histological dating of endometrium was two or more days behind. The results showed that histological abnormality and low P level were 6.3% and 31.3%, respectively. When histological abnormality combined with lowered P level at the same cycle, the diagnosis of LPD increased to 87.5%. The author suggests that both midluteal phase P level and late luteal endometrial histological examination should be assessed at the same cycle in the diagnosis of LPD. BBT should also be assessed. PMID- 8344088 TI - [Determination of tumor necrosis factor from peripheral blood cells in patients with ovarian cancer]. AB - The production of tumor necrosis factor (TNF) induced by LPS in the peripheral blood mononuclear cells from the patients with malignant and benign ovarian tumors were determined. Decreased production of TNF were observed in the patients with malignant ovarian tumor. In the advanced cases, TNF were lower than that in the early ones, which may indicate the progression of the tumors. These findings suggested that the TNF may be a useful indicator to diagnose the malignant tumors and prognosticate the tumors' developing. PMID- 8344089 TI - [Preliminary trials of immune function of erythrocytes in women with benign or malignant gynecologic tumors]. AB - The immune function of erythrocytes in 74 women with benign or malignant gynecologic tumors were studied by red-cell immune adherence (RCIA), regulating factor of erythrocytes (RFER), inhibiting factor of erythrocytes (RFIR), and factor of promoting neutrocyte of erythrocytes (ERPN). Our results indicated that RCIA, RFER, and ERPN in women with malignant tumors were lower than those of normal and with benign tumors (P < 0.001). The RFIR of women with malignant tumors was higher than others (P < 0.001). Meanwhile, the changes of immune function of erythrocytes during treatment were compared and discussed. Our data suggested that women with malignant gynecologic tumors had lower immune function of erythrocytes. PMID- 8344090 TI - [A preliminary cytogenetic study of uterine leiomyoma]. AB - Thirty fresh samples of uterine leiomyoma were disaggregated in collagenase (200kU/L) and cultured for 3-10 days with incubator. Of 30 cases, 27 cases of uterine leiomyoma obtained karyotypes and the rate of successful cultured was 90%, 9 cases showed abnormal karyotypes. Structural changes were frequently seen. Breakpoint of chromosome were 12q13-15 (7 cases), 14q24 (6 cases), 7q31-32 (3 cases). Specific chromosomal rearrangements were t(12;14) (q13-15; q24) and del (7) (q31-32). Our data suggested that chromosome 12q13-15, 14q24, 7q31-32 may be related to the proliferation of uterine leiomyoma. PMID- 8344091 TI - [Relation between the incidence of ectopic pregnancy and the use of intrauterine devices]. AB - The relationship between the incidence of ectopic pregnancy (EP) and the use of IUD was examined by the method of analytical epidemiological study. 10,843 women of child-bearing age from the west district of Beijing were investigated. The conclusions were: (1) The incidence of EP in IUD users was 0.91/1,000 women year; and the EP incidence in women not using any contraceptives was 2.23/1,000 women year. (2) The incidence of EP in women with IUD inserted within 2 years was significantly higher than that in women using IUD longer than 2 years, that is 5.64/1,000 women year and 0.47/1,000 women year respectively. (3) The probability of suffering from EP for accidental pregnancy in IUD users was 4.84%, which was much higher than that of women not using any contraceptives (0.20%). (4) The risk of EP for IUD users with pelvic inflammatory disease was 6.64 times compared to those without pelvic inflammatory disease. (5) EP was not related to previous cesarean section or induced abortion. PMID- 8344092 TI - Intestinal epithelial function: the case for immunophysiological regulation. Cells and mediators (1). AB - During the last decade the traditional view of epithelial function being controlled solely by the endocrine and nervous systems has been expanded by the realization that immune cells also have an important part to play in the control of intestinal physiology. Here, we review the current immunophysiological data pertaining to the control of the function of the intestinal epithelium, with particular reference to ion secretion. The role of immunocompetent cells (lymphocytes, mast cells, and granulated phagocytes) and their chemical messenger molecules (ie, biogenic amines, eicosanoids, cytokines) is discussed and the general theme of cell cooperation and integration is emphasized. PMID- 8344093 TI - Effects of PEG-electrolyte (Colyte) lavage on serum acetaminophen concentrations. A model for treatment of acetaminophen overdose. AB - The purpose of this study was to evaluate whole gut lavage with polyethylene glycol electrolyte solution (Colyte), as a potentially adjunctive measure in lowering serum acetaminophen levels. The effect of bowel lavage was evaluated on serial serum acetaminophen concentrations after 2-g and 4-g doses in 7 and 12 male patients, respectively. Mean peak level of serum acetaminophen after 2 g (60 min after intake) was not significantly lowered by bowel lavage. After 4 g, peak acetaminophen serum levels were significantly lower after bowel lavage (65.4% of controls, P < 0.001). Urinary concentrations of the mercapturic acid conjugate of the toxic metabolite were also significantly reduced by lavage (55% after 2 g and 45% after 4 g, P < 0.01). Activated charcoal given orally after administration of 4 g of acetaminophen had no significant effect on peak serum levels and had no additive effect on lavage. These studies suggest that rapid, complete bowel lavage with a polyethylene glycol electrolyte solution may be beneficial as an adjunct to the treatment of the acetaminophen intoxication. PMID- 8344094 TI - The symptom index. Differential usefulness in suspected acid-related complaints of heartburn and chest pain. AB - The symptom index is a quantitative measure developed for assessing the relationship between gastroesophageal reflux and symptoms. Controversy exists, however, over its accuracy and the appropriate threshold for defining acid related symptoms of heartburn and chest pain. Therefore, a retrospective review was done of 153 consecutive patients referred to our esophageal laboratory. Three groups were identified: patients with normal 24-hr pH tests and no esophagitis, patients with abnormal 24-hr pH tests and no esophagitis, and patients with abnormal 24 hr pH values and endoscopic esophagitis. If symptoms occurred during the pH study, a symptom index (number of acid related symptoms/total number of symptoms x 100%) was calculated separately for heartburn and chest pain. Heartburn and chest pain episodes were similar among the three groups. However, the mean symptom index for heartburn was significantly (P < 0.001) higher in the patient groups with abnormal pH values [abnormal pH/no esophagitis: 70 +/- 7.1% (+/- SE); abnormal pH/esophagitis: 85 +/- 4.6%] as compared to those with normal studies, ie, functional heartburn (26 +/- 10.7%). The mean symptom index for chest pain was similar for all three groups. Using receiver operating characteristic curves, a heartburn symptom index > or = 50% had excellent sensitivity (93%) and good specificity (71%) for acid reflux disease, especially if patients complain of multiple episodes of heartburn. In contrast, an optimal symptom index threshold for defining acid-related chest pain episodes could not be defined. PMID- 8344095 TI - Outcome after perforation sustained during pneumatic dilatation for achalasia. AB - Although esophageal perforation complicates about 5% of pneumatic dilatations performed for achalasia, little is known about associated hospital and long-term courses. In order to assess the outcome of such patients undergoing emergency surgery for repair, records of seven patients sustaining perforation during pneumatic dilatation were compared to those of five patients undergoing elective myotomy during the same period. In perforation patients, mean intervals following the procedure were 3.6 hr to administration of antibiotics and 9.6 hr to surgery. The perforation and elective myotomy groups had similar mean durations of operation (3.8 vs 3.3 hr), intensive care stays (2 vs 1 days) and hospitalization (12 vs 11 days); perforation patients had a significantly longer mean interval from surgery to oral intake (7 vs 5 days). Postdischarge long-term outcomes were alike in the groups. It is concluded that patients with perforation from pneumatic dilatation that is recognized and treated promptly have outcomes that are comparable to those of patients who undergo elective myotomy. PMID- 8344097 TI - Gastric emptying and bezoars in Japanese. Report of five cases. AB - Bezoars are conglomerates of undigested material in the stomach. Previous reports have shown that a decrease in secretion of pepsin and gastric acid and a delay in gastric emptying might contribute to their formation. To clarify the pathogenesis of the formation of gastric bezoars, we studied gastric emptying in five patients who presented with a bezoar. In addition, gastric acid secretion was studied in three of the cases. Gastric emptying was not delayed in any case, and there was no trend toward a decrease in gastric acid secretion. The five patients were successfully treated by the endoscopic fragmentation and enzymatic dissolution of the bezoars. We conclude that, in Japanese, factors other than a delay in gastric emptying are the main contributors to bezoar formation. PMID- 8344096 TI - Markers of slow-healing peptic ulcer in the elderly. A study on 1,052 ranitidine treated patients. AB - Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearson's chi-squared tests and Cox's models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P = 0.002) and persisting ulcer symptoms (P = 0.0001); indicators of slow-healing DU were ulcer size (P = 0.0001), persisting ulcer symptoms (P = 0.0001), alcohol (P = 0.0003), and NSAID (P = 0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P = 0.0352).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344098 TI - Circadian rhythm in aspirin (ASA)-induced injury to the stomach of the fasted rat. AB - Circadian rhythms exist in several gastric parameters affecting ulcerogenesis. This study investigated possible circadian rhythmicity in observed aspirin (ASA) induced gastric lesions in the rat. In five experiments 183 rats were studied at 14 time points over a 24-hr period. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18 hr, then given oral acidified ASA. One hour later, the rats were sacrificed, the stomachs were removed, stretched flat, photographed, scanned, and measured for percent area of gross lesions in the gastric corpus by computer planimetry. Cosinor rhythmometric analysis showed a significant (P < 0.001) rhythm. Mean of rhythm (MESOR) was 5.60 +/- 0.25% of total corpus. Amplitude was 25.89 +/- 6.07% of MESOR. Peak time (acrophase) was 1909 +/- 0101 hr after lights on. Thus, gastric vulnerability to ASA injury exhibited circadian rhythmicity with peak injury during the dark period in this species. PMID- 8344099 TI - Nicotine has no effect on rat gastric mucosal prostaglandin generation in vitro. AB - Previous studies have shown that cigarette smoking depresses prostaglandin generation by human gastric mucosa, but the component of smoke that is responsible for that action is not known. To investigate whether nicotine has a direct effect on gastric mucosal prostaglandin generation, we performed the following study. Eight rats were sacrificed and the stomachs removed. Using a biopsy forceps, small pieces of gastric mucosa were resected and placed in incubation vials containing either buffered Krebs solution alone (control), Krebs solution plus indomethacin (5 micrograms/ml), or Krebs solution plus one of several concentrations of nicotine ditartrate (10, 100, 500, 1000 ng/ml). The nicotine concentrations we used ranged below and above the plasma nicotine concentrations of smokers shortly after smoking cigarettes. Three separate incubations of gastric mucosa were performed per experimental group from each animal. After 30 min of incubation, prostaglandin E2 and 6-keto-prostaglandin F1 alpha concentrations in the incubation medium were measured by radioimmunoassay. We found that nicotine at any concentration tested had no effect on the generation of prostaglandin E2 and 6-keto-prostaglandin F1 alpha by rat gastric mucosa. Thus, this study indicates that, if nicotine is involved in the depression of prostaglandin generation in the gastric mucosa of smokers, its role is an indirect one and not by direct action on the gastric mucosa. PMID- 8344100 TI - Association between gastrointestinal tract carriage of Candida, blood group O, and nonsecretion of blood group antigens in patients with peptic ulcer. AB - Of 112 patients with peptic ulcer disease examined for oral carriage of Candida, 66 (59%) were carriers. Candida carriage was associated with blood group O (P < 0.05) and, independently, with nonsecretion of blood group antigens (P < 0.01). For each subject, the presence or absence of yeasts was found to be a constant characteristic, and only among patients positive for Candida was blood group O or nonsecretion more frequent than expected in the general population. The quantity of yeasts isolated was significantly greater in patients than in normal subjects (P < 0.002), as was the frequency of carriage in the patient population (59% vs 32%). This increase was not associated with treatment with H2-receptor antagonists. The results of paired oral and gastroduodenal aspirate cultures suggested that identifying Candida in the oral cavity was a good indicator of the presence of yeasts elsewhere in the gastrointestinal tract. Mechanisms whereby overgrowth of Candida in the upper gastrointestinal tract might contribute to the inflammatory background of peptic ulcer disease are discussed. PMID- 8344101 TI - Early evening dosing of ranitidine. Comparison with nighttime dosing of ranitidine or cimetidine in duodenal ulceration. AB - A double-blind multinational comparison of ranitidine 300 mg post evening meal (pem), ranitidine 300 mg nocte and cimetidine 800 mg nocte has been carried out in 1677 patients with endoscopically verified duodenal ulcer disease. Fifty-three percent of ulers healed by two weeks during treatment with ranitidine 300 mg pem and 88% by four weeks, while the results for ranitidine 300 mg nocte were 50% and 86%, respectively, and 44% and 84% for cimetidine. The difference between ranitidine 300 mg pem and cimetidine was significant at two weeks (P = 0.002, Mantel-Haenszel chi-squared test). The relative efficacy of the treatments was not dependent upon gender, smoking habit, alcohol intake, or ulcer frequency. However, the overall differences in healing between patients with small and large ulcers and patients with single and multiple ulcers were significantly different at weeks 2 and 4 (P < 0.001). Significantly more patients treated with ranitidine (60%) had complete relief of epigastric pain than those treated with cimetidine (54%) (P < 0.05). A meta-analysis of the four double-blind comparisons of ranitidine 300 mg pem (N = 841) and 300 mg nocte (N = 849), including the present study, failed to show the benefits of pem dosing, predicted from pharmacological studies. PMID- 8344102 TI - Relationship between tissue calcium content and duodenal ulcer in the rat. AB - Since the effect of cellular calcium on cell injury has been in question, this study focused on the relationship between tissue calcium content and cysteamine induced duodenal ulcer. Rats treated with cysteamine showed a high frequency and severity of duodenal ulcer, and the calcium content in the duodenal mucosa was elevated. Furthermore, the level of calcium content in duodenal mucosa was positively associated with the severity of the duodenal lesion. Whereas administration of calcium increased duodenal ulcerative response to cysteamine, verapamil afforded protection against ulceration. We conclude that calcium accumulation in duodenal mucosa is related to duodenal ulceration induced by cysteamine. PMID- 8344103 TI - Alpha-smooth-muscle actin expression in normal and fibrotic human livers. AB - To determine the significance of the expression of alpha-smooth-muscle actin in the fibrotic human liver, normal and diseased livers were stained with anti-alpha smooth-muscle-actin antibody by an immunoperoxidase method. Vitamin A-containing lipocytes were also identified by the modified Kupffer's gold chloride method. In the normal human liver, lipocytes as well as vascular smooth muscle cells expressed alpha-smooth-muscle actin. In alcoholic liver disease, there was an increase in the cells positive for alpha-smooth-muscle actin adjacent to the fibrotic areas, but the response of lipocytes to the gold chloride reaction diminished. In chronic hepatitis, the cells positive for alpha-smooth-muscle actin increased around the enlarged portal areas, and the response to the gold chloride reaction did not change appreciably. An increase in the cells positive for alpha-smooth-muscle actin was associated with the progression of hepatic fibrosis in the liver of patients with alcoholic liver disease and chronic hepatitis. PMID- 8344104 TI - Practice and complications of liver biopsy. Results of a nationwide survey in Switzerland. AB - Studies on the complication rate of liver biopsy have hitherto been conducted in referral hospital centers. They are therefore not representative for general practice where liver biopsy is performed by specialists and nonspecialists. In a postal nationwide survey, we approached all gastroenterologists and hospital internists to assess the complication rate and practice (setting, needle type, use of ultrasonography) of percutaneous liver biopsy performed in 1989 in Switzerland for diffuse liver disease. Two hundred eighty questionnaires were mailed and 252 were returned (response rate 90.0%) 165 respondents (65.5%) performed 3501 biopsies while 87 respondents (34.5%) did not practice liver biopsy; 67.7% of biopsies were executed blindly and 32.3% were guided. Eight nonfatal and three fatal complications occurred. Hemorrhage was the most frequent complication (five cases) and was responsible for all three fatal outcomes. The overall complication rate was 0.31%, being distinctly lower in the group of gastroenterologists (0.11%) as compared to the group of internists (0.55%; P = 0.031). The complication rate was 1.68% in the group of internists performing fewer than 12 biopsies per year, while there was no complication in the group of internists performing more than 50 biopsies per year (P = 0.036). Complications were not related to the needle diameter or to the absence of ultrasonography before biopsy. In conclusion, this representative survey in Switzerland shows that the complication rate of liver biopsy is mainly related to the experience and training of the operator. PMID- 8344105 TI - Gender of donor influences outcome after orthotopic liver transplantation in adults. AB - Because male and female livers not only differ with respect to estrogen and androgen receptor content, but also demonstrate sexual dimorphism of certain functions, we examined the effect of donor gender on graft survival following liver transplantation (OLTx) in adults. Between February 1981 and February 1988, 982 OLTx procedures were performed in 789 adult patients at the University of Pittsburgh. In this study, OLTx was categorized as a failure if the patient died or required retransplantation within 60 days of the surgery. When the donor recipient gender combinations were male-male, male-female, and female-female, the failure rates were 28%, 28%, and 36%, respectively. In contrast, 60% of female donor livers failed in male recipients. Compared to the pooled donor-recipient gender combinations, the odds of failure for female-male liver grafts were increased 3.7-fold (95% confidence interval: 6.5, 2.1; P < 0.001). These findings may result, at least in part, from alterations in the sex hormone milieu or changes in the graft estrogen or androgen receptor content. PMID- 8344106 TI - Effect of cyclosporine on liver regeneration after orthotopic reduced-size hepatic transplantation in the rat. AB - These experiments were undertaken to study the effects of cyclosporine A (CsA) on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation (RSHT) in rats. Male Wistar rats were treated with or without a daily injection of CsA beginning 24 hr before surgery and were subjected to a 68% partial hepatectomy. A isogeneic orthotopic reduced-size hepatic transplantation was performed in recipient rats pretreated with or without CsA. A daily injection of CsA was continued until the recipient rats were sacrificed. Animals were sacrificed at various time points (12, 24, 36, 48, and 72 hr) postoperatively. The incorporation of bromodeoxyuridine (BrdU) into the DNA of the remnant hepatocytes was evaluated by immunohistochemical staining with a monoclonal antibody against BrdU. CsA (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index (LI) was observed at 24 hr after hepatectomy. In contrast, the maximum LI in the recipient rats not receiving CsA was seen at 36 hr after RSHT, and 10 mg/kg/day of CsA decreased the LI at 36 hr after RSHT. A lower dose of CsA (3 mg/kg/day), however, significantly increased the LI in the recipient rats (P < 0.01), and it reached a peak at 24 hr after RSHT when compared to the transplant recipients not receiving CsA. The time course of the increase in the LI in the transplant recipient rats receiving 3 mg/kg/day of CsA was similar to that observed in the rats after hepatectomy. This dosage improved the delay in the reduced-size hepatic transplant LI reaching its peak.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344107 TI - Maternal malnutrition does not affect fetal hepatic glycogen synthase ontogeny. AB - Maternal malnutrition late in pregnancy results in the reduced storage of fetal hepatic glycogen in the final days of gestation and an accentuation of normal birth-related hypoglycemia. It was of interest to determine whether or not low glycogen levels resulted when maternal malnutrition disrupted the normal ontogeny of fetal hepatic glycogen synthase, an important glycogenic enzyme. A defect in this enzyme would be expected to seriously affect prenatal and postnatal glycogen synthesis. For this study, livers were removed from fetuses from malnourished (50% of normal dietary intake) mice, as well as from ad libitum-fed mice, and used for the determination of hepatic glycogen, glycogen synthase activity, and glycogen synthase protein levels. In this paper we report that maternal dietary restriction late in pregnancy produces growth-retarded fetuses with severely reduced hepatic glycogen levels, but the normal ontogenic changes in the quantity and activity of hepatic glycogen synthase were not affected. It is especially significant that the accumulation of glycogen synthase occurred despite the minimal level of natural substrate available for the enzyme. These results suggest that the accumulation and activity of hepatic glycogen synthase during late gestation is related to developmental events rather than levels of substrate or glycogen. PMID- 8344108 TI - Prophylactic versus emergency sclerotherapy of large esophageal varices prior to liver transplantation. AB - From January 1985 through July 1987, adult patients accepted for liver transplantation with large esophageal varices were enrolled in a study evaluating the use of prophylactic vs emergency sclerotherapy. Six hundred forty-eight subjects received prophylactic sclerotherapy, and 172 received emergent sclerotherapy. Esophageal stricture formation was increased 12.9-fold (P < 0.001), esophageal perforation 6.4-fold (P < 0.005), and postsclerotherapy bleeding esophageal ulcers 3.7-fold (P < 0.001) in those receiving emergency sclerotherapy as opposed to prophylactic sclerotherapy. These differences were even greater if the number of sclerotherapy sessions rather than the number of patients was used as the denominator for the comparisons. In total, 19.6% of emergency sclerotherapy cases were associated with an untoward outcome of sclerotherapy; only 1.9% of cases receiving prophylactic sclerotherapy experienced an untoward outcome (P < 0.001). These data demonstrate that emergency sclerotherapy is associated with a greater prevalence of complications and support earlier studies that show that sclerotherapy prevents variceal bleeding over the short term. The data also suggest that when applied to patients with large varices awaiting orthotopic liver transplantation, it enhances the chance of a patient surviving to be transplanted by preventing a variceal bleed and the spiral of liver failure and death that frequently follows an episode of acute variceal bleeding. PMID- 8344109 TI - Abnormal progression of a liquid meal through the stomach and small intestine in patients with Chagas' disease. AB - This study describes the abnormal pattern of gastrointestinal progression of a liquid meal in patients with the digestive form of chronic Chagas' disease. This condition is known as a natural model of intramural denervation of the gut. Sixteen patients with clinical and radiographic evidence of esophageal and/or colonic involvement and 18 healthy volunteers were studied. Orocecal transit time after the ingestion of a 10% lactulose solution (180 ml) tagged with 99mtechnetium was measured by a conventional H2 breath technique. Gastric emptying and the arrival of the front of the meal to regions of interest corresponding to proximal and distal areas of the small intestine were assessed by abdominal scintigraphy. Orocecal transit time was significantly greater (P < 0.05) in Chagas' disease patients (N = 13) than in control subjects (N = 18) (mean +/- SD: 100.7 +/- 48.7 min vs 62.9 +/- 18.2 min). Half-time for gastric emptying of liquids in chagasic patients (N = 9) was significantly lower (P < 0.01) than in controls (N = 7) (9.7 +/- 2.7 min vs 26.4 +/- 3.4 min). The time of arrival of the liquid meal to the proximal small intestine was also significantly shorter (P < 0.02) in patients than in controls (5.6 +/- 3.7 vs 11.4 +/- 5.5 min), but there was no difference between the two groups concerning the time the meal first arrived to the distal small intestine (15.0 +/- 11.0 min vs 23.5 +/- 11.4 min, P > 0.05). These results indicate that patients with Chagas' disease have a combination of exceedingly rapid gastric emptying and abnormally delayed transit of liquids through the more distal segments of the small bowel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344111 TI - Anorectal dysfunction and delayed colonic transit in patients with progressive systemic sclerosis. AB - We studied 14 unselected patients with progressive systemic sclerosis (PSS), six with constipation, and eight with normal bowel habits. A control group, matched for age and sex, comprised six patients with idiopathic constipation and seven healthy subjects. Anorectal manometry was performed with perfused catheters and segmental colonic transit was measured by a radiopaque marker technique. The resting pressure of the anal canal was significantly reduced in PSS with constipation (P < 0.05). The rectoanal inhibitory reflex was detected in only one PSS patient with constipation, but was present in seven of eight PSS patients with normal bowel habits and in all controls (P < 0.01). Total and right colonic transit times were significantly delayed in PSS with constipation and in patients with idiopathic constipation (P < 0.05). In patients with PSS, colonic transit was delayed and anal sphincter function was impaired in constipated patients, suggesting involvement of both the colon and the anorectum by the disease. PMID- 8344110 TI - Electrogastrography in patients with gastroparesis and effect of long-term cisapride. AB - Abnormalities in the gastric pacemaker potentials occur in patients with impaired gastric emptying. It is unclear if treatment effects the underlying rhythm or if normalization of dysrhythmias is important. We examined the effect of cisapride using surface electrogastrograms and radionuclide gastric emptying studies of patients with idiopathic and diabetic gastroparesis. Twelve of 14 patients had abnormal baseline electrogastrograms. After six months of cisapride, four patients had normalization of their electrical activity and six had improvement. Patients with idiopathic gastroparesis had an increase in gastric emptying at 120 min from 48.9 +/- 3.8% (baseline) to 70.9 +/- 6.0% (six months), P = 0.009. Patients with diabetes mellitus had a similar improvement. Patients who had normalization of the electrogastrogram had a greater gastric emptying rate than patients with continued dysrhythmias. Thus, dysrhythmias are important in the etiology for gastroparesis, but other factors need to be examined. PMID- 8344112 TI - Alterations in rat intestinal transit by morphine promote bacterial translocation. AB - Translocation of enteric microorganisms from the intestinal tract to extraintestinal sites has been proposed as an early step in the development of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial translocation using morphine as a pharmacologic inhibitor of such transit. In the first experiment, either normal saline (N = 8) or morphine sulfate (20 mg/kg; N = 8) was injected subcutaneously. Two hours later, morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this regimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) were injected intraduodenally in each group. The bowel was removed 25 min later, divided into 5-cm segments, and the content of dextrans measured. Small bowel propulsion was expressed as the geometric center of the distribution of dextrans throughout the intestine (in percentage length of small bowel). Gut propulsion was significantly reduced after morphine treatment as compared to controls (32.8 +/- 8.2% vs. 55.8 +/- 4.0%; P < 0.01). In 16 additional rats, saline or morphine was again administered as described. After 24 hr, samples were obtained from the mesenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, jejunum, ileum, and cecum for standard bacteriology. The bacterial counts increased significantly in each intestinal segment following morphine treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344113 TI - Lithocholate-3-O-glucuronide-induced cholestasis. A study with congenital hyperbilirubinemic rats and effects of ursodeoxycholate conjugates. AB - The mechanism of lithocholate-3-O-glucuronide-induced cholestasis is unknown. In this study, we investigated the cholestatic effects of this agent in a congenital hyperbilirubinemic rat, EHBR. We also studied the effects of ursodeoxycholate-3-O glucuronide and tauroursodeoxycholate on lithocholate-3-O-glucuronide-induced cholestasis in rats. Lithocholate-3-O-glucuronide, administered at the rate of 0.1 mumol/min/100 g for 40 min, a cholestatic dose in control rats, failed to cause cholestasis in EHBR, and biliary lithocholate-3-O-glucuronide excretion was delayed. Biliary concentrations of this agent did not correlate with the severity of cholestasis. Both tauroursodeoxycholate and ursodeoxycholate-3-O-glucuronide, infused at the rate of 0.2 mumol/min/100 g for 120 min, completely inhibited cholestasis induced by lithocholate-3-O-glucuronide administered at the rate of 0.1 mumol/min/100 g for 40 min. Only tauroursodeoxycholate enhanced biliary lithocholate-3-O-glucuronide excretion. These findings indicate that lithocholate 3-O-glucuronide-induced cholestasis is induced by damage at the level of the bile canalicular membrane. Ursodeoxycholate-3-O-glucuronide inhibits this cholestasis, possibly by inhibiting the access of lithocholate-3-O-glucuronide to the bile canalicular membrane. PMID- 8344114 TI - Protein-losing enteropathy caused by mesenteric vascular involvement of neurofibromatosis. AB - A 44-year-old man with neurofibromatosis suffered from severe diarrhea and progressive hypoproteinemia. Enteric protein loss was confirmed by an alpha 1 antitrypsin clearance test. An x-ray study showed irregular mucosa in the distal segment of the ileum. Protein loss has subsided after ileocecal resection. Laparotomy and radiological examinations failed to demonstrate neurofibroma or other tumors in the abdomen. The resected ileum revealed marked edema of the wall and a pseudomembranous enteritis-like appearance in the luminal surface. Microscopically, lymphatic vessels in the intestinal wall were dilated. Marked thickening of the intima with spindle cell proliferation was observed in the mesenteric arteries and veins. This finding is consistent with vascular changes in neurofibromatosis. These vascular changes in the mesentery due to neurofibromatosis may cause protein-losing enteropathy by altering the hemodynamic state and microvascular permeability in the intestine. PMID- 8344115 TI - Ganglioneuroma of the duodenum. Report of a case and literature review. AB - A 43-year-old male presented with upper gastro-intestinal bleeding. A polypoid tumor mass in the second part of the duodenum was found by endoscopic examination. Pathology revealed an extremely rare case of ganglioneuroma. The surgical local resection of the tumor was a sufficient procedure because of a lack of malignant potential. This is the fourth case since the first case was reported by Dahl et al in 1957 (1). We review the literature concerning duodenal paragangliomas, and discuss the histogenesis. PMID- 8344117 TI - Achalasia due to eosinophil infiltration: fact or fiction? PMID- 8344116 TI - Treatment of Crohn's disease recurrence after ileoanal anastomosis by azathioprine. AB - Ileoanal anastomosis is a surgical procedure performed in patients with ulcerative colitis. In a small number of patients operated on for ulcerative colitis, Crohn's disease occurs in the reservoir, mimicking pouchitis, and may lead to pouch excision and to a permanent terminal ileostomy. Two patients with recurrent Crohn's disease in the reservoir after ileoanal anastomosis were treated with azathioprine for 18 and 24 months, respectively. Azathioprine induced a complete clinical and endoscopic remission. These two observations suggested that immunosuppressive drugs were a good option for permanent ileostomy in cases of recurrence of Crohn's disease in the reservoir after ileoanal anastomosis. PMID- 8344118 TI - Gallbladder and cisapride. PMID- 8344119 TI - "Passive" gastric mucosal congestion in patients with gastropathy. PMID- 8344120 TI - Genetic factors of importance for beta-cell proliferation. PMID- 8344122 TI - The kidney disease of diabetes mellitus (KDDM): a cell and molecular biology approach. PMID- 8344121 TI - Intensified insulin therapy. PMID- 8344123 TI - Methodologies used in the study of the microcirculation in diabetes mellitus. PMID- 8344124 TI - Inhibitory effect of amiloride on glucose transport in isolated rat adipocytes. AB - The effect of amiloride on 3-O-methylglucose (3-O-MG) uptake was studied in isolated rat adipocytes to define to what extent amiloride inhibited the process of insulin action or glucose transport. Amiloride (1 mM), which did not change the intracellular water space of adipocytes, inhibited by 43.3% the insulin stimulated uptake of 3-O-MG, while it did not appear to inhibit the basal uptake. To distinguish the inhibitory effect on glucose transport activity from that on the process of insulin action, the effect of amiloride was evaluated in the transport system using adipocytes deprived of ATP, in which glucose transporters were considered immobile. Amiloride (1 mM) inhibited this transport by 32.8% in an insulin-stimulated state, which was obtained using adipocytes that had been treated with 20 nM insulin and exposed to 2 mM KCN, whereas it did not inhibit the transport system at the basal state. In the inhibitory effect, 76% was thus attributable to the inhibition of glucose transport activity recruited by insulin and 24% to the inhibition of the action of 20 nM insulin itself. These results indicate that amiloride can not be used as a specific inhibitor of the insulin action itself. PMID- 8344125 TI - Apolipoprotein E polymorphism affects the response to pravastatin on plasma apolipoproteins in diabetic patients. AB - In the present study, we examined the levels of plasma lipids and apolipoproteins in patients with non-insulin dependent diabetes mellitus (NIDDM) with hypercholesterolemia in different apolipoprotein E (apo E) phenotypes. We also examined the influences of apo E polymorphism on the response to pravastatin. The patients were divided into three groups, E4/E3, E3/E3, and E3/E2. There were no differences in the baseline levels of plasma lipids and apolipoproteins, except that the level of triglycerides in E3/E2 heterozygotes was significantly higher than E3/E3 homozygotes. Three months of pravastatin administration significantly reduced plasma levels of total cholesterol and low-density lipoprotein cholesterol in each group to the same degree. We observed a significant reduction of apo B both in the E4/E3 and E3/E3 groups and apo E in the E3/E3 group. Such reduction was not observed in the E3/E2 group. We conclude that pravastatin is a potent drug to correct lipid abnormalities, particularly in NIDDM patients with apo E4/E3 and E3/E3. In the E3/E2 group, its effectiveness may be diminished. PMID- 8344126 TI - Production of anti-cardiolipin antibody in AKR/J mice with streptozocin-induced insulitis and diabetes. AB - We herein report that anti-cardiolipin antibodies (ACA) were detected in AKR/J mice treated with multiple low doses of streptozocin (STZ)-induced insulitis and diabetes. Daily intraperitoneal (i.p.) injections of 40 mg/kg body wt. of STZ for five consecutive days in the AKR/J mice resulted in hyperglycemia and mononuclear cell infiltrations of islets (insulitis). ACA appeared on day 14, when hyperglycemia began to occur, at a rate of 13.3% (4/30). The rate increased to 83.3% (25/30) on day 21, when diabetes developed, and then fell to 10% (3/30) on day 28. Neither the diabetic AKR/J mice treated with a single high dose of STZ (200 mg/kg body wt.) nor the non-diabetic insulitis free Balb/c mice and B10.S(9R) mice treated with multiple low doses of STZ (40 mg/kg body wt.) produced ACA. The IgG subclass of the ACA belonged mainly to IgG2a. These findings suggest that ACA are produced in association with the development of insulitis, but not induced by either hyperglycemia or STZ. PMID- 8344127 TI - Effects of a short prednisone regime at clinical onset of type 1 diabetes. AB - The effect of corticosteroids on beta cell function and humoral immune response in type 1 diabetes was tested in a 2-month trial conducted on 32 newly diagnosed patients (age 22.8 +/- 1.4 years, mean +/- S.E.M.). Prednisone was administered at immunosuppressive dosage (1 mg.kg-1.day-1) during the initial 10 days and at a maintenance dosage (0.3 mg.kg-1.day-1) for 50 days. Patients (n = 32) were enrolled within 6 weeks after diagnosis and matched in pairs for age, sex, presence of islet cell antibodies (ICA) and glucagon stimulated C-peptide levels. Insulin discontinuation was not contemplated. All the patients who received prednisone became ICA during treatment but in some (4 out of 10) this effect was only transient. Insulin antibodies (IA) were significantly lower in the prednisone group at second and third month (P < 0.05). No patient experienced complete remission but in 10 prednisone and 4 control patients the insulin requirements were below 0.3 IU/kg (P < 0.05). With similar glycemia the fasting C peptide levels were higher in the treated patients. The profile of the insulin requirements during the follow-up was different in the two groups and at 9 months the prednisone group needed less insulin than the control (P < 0.05). Interestingly, within the prednisone-treated group and after 6 months, the levels of stimulated C-peptide improved significantly among the ICA+ patients while they were steady or declined in ICA- (P < 0.01). The analysis of variance covariance confirmed a positive interaction between ICA and the administration of prednisone on the outcome of beta cell function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344128 TI - Clinical usefulness of a non-wiping type glucose meter in diabetic patients. AB - A non-wiping type glucose meter using electrochemistry was developed. The glucose sensor strip has a sophisticated micro-structure for aspirating blood automatically. The meter compensates for drift of sensor output due to temperature change of the atmosphere. Mounting blood on the sensing site and wiping blood and precise time are no longer required. Range of measurement is 40 500 mg/dl. Reading of the meter for standard solutions of 90 or 360 mg/dl glucose showed negligible drift of measurement from 10.5 degrees C to 38.5 degrees C. The correlation between plasma glucose concentrations as determined by the meter and that by a Glucose Analyzer 2 was 0.995 with a slope of 1.00 and intercept of 0.65 (n = 48). In the case of blood glucose concentration (Y), the values were Y = 1.06X-0.91, r = 0.987, n = 62. This meter is quite easy to use and is highly accurate for glucose monitoring in patients regardless of operation skill. It should thus be readily applicable to diabetic patients. PMID- 8344129 TI - Erythrocyte sorbitol dehydrogenase activity in diabetic patients. AB - An increased polyol-pathway activity is implicated in the pathogenesis of some diabetic complications. Little is known about the sorbitol-dehydrogenase (SDH) activity in diabetic patients, although cataract is described in diabetes as well as in SDH deficiency. Therefore, we studied SDH activity and the relation with complications and with sorbitol accumulation in erythrocytes from 96 type 1 diabetics and 29 age- and sex-matched healthy subjects. When comparing these groups erythrocyte sorbitol (ERY-SOR) was significantly (P < 0.001) increased in the diabetic patients, but no difference in SDH could be demonstrated. In the diabetic patients ERY-SOR was predominantly related to the glycaemia (r = 0.37; P < 0.001). The SDH activity correlated with HbA1 (r = 0.20; P < 0.03). In diabetic patients with severe nephropathy the ERY-SOR value is no longer different from the control value. It was concluded that, in poor metabolic control the SDH activity is increased, which counteracts but does not prevent the sorbitol accumulation nor the genesis of complications. In patients with macroalbuminuria the ERY-SOR decreases to the normal range. Since SDH activity is similar in type 1 diabetics and controls the decreased ERY-SOR in this complication might be due to other metabolic pathways. PMID- 8344130 TI - Insulin resistance in the regulation of lipolysis and ketone body metabolism in non-insulin dependent diabetes is apparent at very low insulin concentrations. AB - The insulin sensitivity of intermediary metabolism was studied in 8 non-obese men with well-controlled diet-treated non-insulin dependent diabetes (NIDDM) using a low dose incremental insulin infusion (basal, 0.005 and 0.01 U/kg h-1). Results were compared to 8 healthy male control subjects matched (NIDDM vs. controls, mean +/- S.E.M.) for age (56 +/- 3 vs. 54 +/- 3 years, NS) and body mass index (24.6 +/- 0.7 vs. 25.3 +/- 0.5 kg/m2, NS). Basal fasting concentrations of insulin (4.7 +/- 0.8 vs. 3.2 +/- 0.8 mU/l, NS), glucose, total ketone bodies (TKB), and non-esterified fatty acids (NEFA) were not significantly different between the groups but glycerol concentrations were significantly elevated in NIDDM patients (0.072 +/- 0.007 vs. 0.049 +/- 0.003 mmol/l, P < 0.05). During incremental insulin infusion, plasma insulin concentrations rose to 12.8 +/- 1.5 vs. 10.0 +/- 1.0 mU/l in NIDDM patients vs. control and metabolite concentrations fell significantly (P < 0.001). Significant linear dose-response relationships were found between plasma insulin (log) and glucose, TKB (log), NEFA, and glycerol concentrations by analysis of variance applied to regression (all P < 0.001). For glucose and TKB (log), the group regression lines were parallel but were significantly right-shifted in the NIDDM group (P < 0.001). In contrast, the relationships of insulin (log) and both glycerol and NEFA concentrations converged over the observed range of insulin concentrations. Significant displacement of glycerol and NEFA dose-response relationships were found in NIDDM patients at an insulin concentration of 5 mU/l (P < 0.001) but not at 12.5 mU/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344131 TI - Higher serum insulin level due to greater total body fat mass in offspring of patients with essential hypertension. AB - To determine whether the offspring of hypertensive patients (OHP) might have a higher serum insulin level than offspring of normotensive parents, we studied 152 girls in junior high school, 21 of whom had at least one hypertensive parent. The remaining 131 girls had normotensive parents and served as the controls. After an overnight fast, we measured the subjects' height, body weight, blood pressure and body fat mass, and collected blood for assay of serum immunoreactive insulin (IRI), lipids and apolipoproteins. Despite a similar body mass index, the OHP had a significantly greater body fat mass (P < 0.05) and % fat mass (P < 0.05) than the controls. The OHP exhibited a significantly higher serum IRI level than the controls (P < 0.05), but no differences in blood pressure or serum lipids. In the OHP, % body fat mass was significantly correlated with systolic blood pressure (P < 0.05), triglyceride (P < 0.01) and apolipoprotein B (P < 0.01), not observed in controls. The serum IRI of the OHP, but not that of controls, was significantly correlated with systolic blood pressure (P < 0.05), serum triglyceride (P < 0.02) and apolipoprotein B (P < 0.05). Thus, a higher serum IRI level due to an increase in total body fat mass appears to be an inherited trait that contributes to the development of hypertension and dyslipidemia. PMID- 8344132 TI - Multiple insulin injection therapy using an insulin pen--who benefits? A clinical 3-year follow-up study of 100 type 1 and 51 type 2 diabetic patients. AB - The present study was undertaken with the aim of evaluating the effect of multiple insulin injection therapy with an insulin pen in a large population of type 1 and type 2 diabetes patients and to investigate which factors predict a favorable response to the therapy change. We included 100 type 1 and 51 type 2 patients with a minimum diabetes duration of 1 year who were followed for at least 3 years after changing from conventional insulin regimens to multiple insulin injection therapy with the pen. Both type 1 and type 2 patients were significantly improved with respect to metabolic control at 3 months. After 1 year type 1 patients were no longer significantly improved compared to baseline. In type 2 patients a significant improvement was sustained for a longer period but at 3 years HbA1c had reverted towards the baseline level. Both type 1 and type 2 patients experienced a significant increase in body weight. Baseline metabolic control was strongly and inversely related to subsequent decline in HbA1c in both type 1 and type 2 patients. Those with initial poor control had a sustained improvement throughout follow-up, whereas those with initial very good control deteriorated significantly. No sustained change was noted in those in intermediate control. In addition, in type 1 patients a high body mass index at baseline was a weak negative predictor for improvement. In type 2 patients a longer duration of diabetes was a favorable factor. Both type 1 and 2 patients in poor control may be expected to benefit from multiple injection therapy. PMID- 8344133 TI - A microsatellite polymorphism in the human insulin receptor gene: a highly informative marker for linkage analysis. AB - To study genetic susceptibility to non-insulin dependent diabetes mellitus (NIDDM), association of insulin receptor gene, a candidate gene for NIDDM, with NIDDM was studied. A microsatellite polymorphism located in intron 2 of the human insulin receptor gene was detected by the polymerase chain reaction and used as a genetic marker. Eight different alleles were observed, indicating highly polymorphic nature of this marker. Although no association of this marker with NIDDM was observed in Japanese subjects, this marker will be useful for linkage studies of insulin receptor gene and genes located close to this gene on chromosome 19. PMID- 8344134 TI - Diabetes mellitus and hypertension based on the family history and 2-h postprandial blood sugar in the Ann-Lo district (northern Taiwan). AB - From July 1988 to June 1990, we performed an epidemiological study on the prevalence of hypertension and diabetes mellitus (DM) in the Ann-Lo district, a suburban area of Northern Taiwan. One third of the population in the district was randomly sampled. A total of 9087 persons were screened with 67.4% participating. Following completion of the questionnaire blood pressure, 2 h postprandial blood sugar were determined. DM was defined when the blood sugar was over 200 mg/dl or the subject had a diabetic history. Hypertension was defined if the systolic blood pressure was over 160 mmHg or the diastolic blood pressure over 95 mmHg. Statistical comparisons were performed with a chi-square test, analysis of covariance, stepwise multiple regression and Pearson correlation matrix. In this study, the prevalence rate of DM was 2.6% and of hypertension was 6.4%. For those patients 40 years or older, the prevalence rate for DM was 8.0% and for hypertension was 19.7%. The prevalence of hypertension was 24.8% in overt diabetes and 5.2% in the normal subjects. Analysis of the data between risk factors of DM revealed that DM correlated with age, body mass index, hypertension, smoking, family history of DM and correlated negatively with education. Hypertension correlated with gender, alcohol intake and smoking, sugar level, age and body mass index. The prevalence rate of diabetes and hypertension were quite high in the district and this study pointed out the important risk factors for hypertension and DM in Taiwan. PMID- 8344136 TI - Drug costs and treatment choices: a DTB symposium. PMID- 8344135 TI - Radioiodine for the treatment of thyroid disease. PMID- 8344137 TI - DTB position on drug costs. PMID- 8344138 TI - Angioplasty in the management of coronary artery disease. PMID- 8344139 TI - Flosequinan for chronic heart failure? PMID- 8344140 TI - Adenosine for acute cardiac arrhythmias. PMID- 8344142 TI - Benzodiazepine dependence--a helpful new report. PMID- 8344141 TI - Azelaic acid--a new topical treatment for acne. PMID- 8344143 TI - Managing high blood pressure in pregnancy. PMID- 8344144 TI - Mifepristone/gemeprost to abort early pregnancy. PMID- 8344146 TI - Typhoid vaccines--which one to choose? PMID- 8344145 TI - Hypoglycaemia and human insulin. PMID- 8344147 TI - Drugs affecting 5-hydroxytryptamine function. PMID- 8344148 TI - Hormonal emergency contraception. PMID- 8344149 TI - Getting to see your GP. PMID- 8344150 TI - [Environmental protection in the hospital as a task for nursing administration]. PMID- 8344152 TI - [Possibilities and limitations of the organization of environmental protection in the hospital]. PMID- 8344151 TI - [The treat to the female gender by environmental poisons]. PMID- 8344153 TI - [Analysis of ecological weaknesses as a starting point for environmentally oriented hospital management]. PMID- 8344154 TI - [Economic value of nursing equipment]. PMID- 8344155 TI - [Tasks and methods of disposable equipment commissions]. PMID- 8344156 TI - [Effective and environment-friendly methods of disinfection in surgery]. PMID- 8344157 TI - [The reduction of hospital waste from the producer's viewpoint]. PMID- 8344158 TI - [The Bavarian work group "Environmental Protection in the Hospital"]. PMID- 8344160 TI - [The packaging legislation. For the application of packaging legislation in health related institutions]. PMID- 8344161 TI - [Violation of confidentiality by the use of telefax devices]. PMID- 8344159 TI - [Cotton diapers versus disposable diapers]. PMID- 8344162 TI - [Producing a testament in the hospital]. PMID- 8344163 TI - [Nursing personnel regulation--not just a request for personnel?]. PMID- 8344165 TI - [Hygienic hand disinfection]. PMID- 8344164 TI - [Pathways of infection in instrumental urinary diversion. The permeation by microorganisms of the balloon of Foley catheters]. PMID- 8344166 TI - [Report of experiences of members of the work group "Nursing Research" at the Bamberg hospital]. PMID- 8344167 TI - [Primary hyperreninemia. An unusual cause of secondary arterial hypertension]. AB - In 1975, scintigraphy revealed a 6.5 x 5 cm tumour in the region of the left adrenal in a 36-year-old man with known hypertension for 5 years (systolic pressure up to 250 mm Hg, diastolic up to 130 mm Hg). A laparotomy was performed for a suspected phaeochromocytoma. A tumour was located in the upper pole of the kidney and removed together with the kidney. The blood pressure quickly returned to normal after the operation: it remained stable for the following 17 years (between 130/80 to 150/90 mm Hg). Originally the tumour could not be clearly classified either clinically or histologically. But recently the paraffin imbedded tumour specimen was re-examined by immunohistochemistry and in-situ hybridization. This identified a renin-producing tumour so that primary reninism was the cause of the arterial hypertension. PMID- 8344168 TI - [Granulocytic functional disorders: forms and diagnosis]. PMID- 8344169 TI - [Opinion of the Federal Constitutional Court on abortion]. PMID- 8344170 TI - [Coagulation parameters in high-dosage intravenous heparin therapy]. PMID- 8344171 TI - [Hyposensitization treatment]. PMID- 8344172 TI - [Prevention of early-summer meningoencephalitis]. PMID- 8344173 TI - [Halofantrine in the treatment of imported malaria in non-immune travelers]. PMID- 8344174 TI - [Contrast medium colonoscopy]. PMID- 8344175 TI - [Juxtapapillary duodenal diverticulum]. PMID- 8344176 TI - [Penicillin-resistant pneumococci]. PMID- 8344177 TI - Acute suppurative otitis media. PMID- 8344178 TI - Severe laryngitis and Reinke's edema. PMID- 8344179 TI - Endoscopic view of sphenoid sinus cavity. PMID- 8344180 TI - The objective assessment of nasal patency. PMID- 8344181 TI - Antrochoanal polyposis: a review of 33 cases. AB - We report on a series of 33 consecutive cases of antrochoanal polyp (ACP) treated by endoscopic sinus surgery over a five-year period. All but one patient was treated by endoscopic sinus surgery alone. This method of treatment was quite effective for ACPs. These 33 patients represent 22.3% of all nasal polyp patients on whom we operated during the same period. This incidence of ACP is greater than that generally reported in the literature. Some authors have attempted to distinguish ACPs from common nasal polyps primarily on the basis of morphology, histology, and the clinical behavior of the ACPs. In our series, a multivariate analysis, including histopathologic correlation, did not support the notion that ACPs are clearly distinct from common nasal polyps. Some interesting differences between the polyp groups did, however, become evident in our data analysis. Generally, ACPs are not thought to be associated with allergic disease; however, in our series we found the association of allergic disease with ACPs to be statistically significant (Chi-square = 4.575, p < .05). PMID- 8344182 TI - Symptom relief after endoscopic sinus surgery: an outcomes-based study. AB - Previous studies of patients outcomes after sinus surgery have generally described only a summary measure of overall change in symptoms or health status. This paper describes an outcomes-based longitudinal study of sinus symptom prevalence among thirty-one patients treated with endoscopic surgery for chronic sinusitis. Patients completed structured data collection forms to quantify the prevalence of commonly experienced sinus-related symptoms during an eight-week period both before surgery and six months after undergoing sinus surgery. Significant decreases in nasal symptom prevalence (post-surgery versus pre surgery) were noted for headaches, nasal drainage, nasal congestion, sinus infection, and breathing difficulties. In addition, the proportion of subjects who rated their current health as "better" compared to one year previously increased from 27% pre-surgery to 58% six months after sinus surgery. These findings aid in quantifying the magnitude of improvement experienced by sinus surgery patients and provide further evidence that endoscopic sinus surgery represents an effective treatment for chronic sinusitis. PMID- 8344183 TI - Physician office laboratories and federal regulation with special attention to allergy testing. PMID- 8344184 TI - Allergic rhinosinusitis: the total rhinologic disease. PMID- 8344185 TI - Atopic keratoconjunctivitis (AKC). PMID- 8344186 TI - Are we facing the end of the antibiotic era? PMID- 8344187 TI - Estradiol acts via the estrogen receptor in the sexual differentiation of the rat brain, but what does this complex do? PMID- 8344188 TI - Enduring consequences of neonatal treatment with antisense oligodeoxynucleotides to estrogen receptor messenger ribonucleic acid on sexual differentiation of rat brain. AB - Sexual differentiation of the mammalian brain is regulated by steroids during a critical developmental period, particularly by estradiol, which is believed to be aromatized in brain from gonadally derived testosterone. To ascertain the importance of neuronal estrogen receptor expression during sexual differentiation, we infused a 15-mer oligodeoxynucleotide antisense to the region of the translation start codon of estrogen receptor messenger RNA (mRNA), into the hypothalamus of 3-day-old rat pups. Two separate control treatments consisted of either a scrambled nucleotide sequence oligodeoxynucleotide, which had little homology to known mRNAs, or vehicle. Female pups either received a lightly androgenizing dose of testosterone 6 h after oligo infusion or were not hormone treated. Infusion of antisense oligo to estrogen receptor mRNA protected against many of the androgenizing effects of testosterone. Androgenized females infused with antisense oligo were significantly more likely to exhibit female sexual behavior in adulthood after treatment with estrogen plus progesterone and remained sensitive to the induction of wheel-running behavior by estrogen treatment seen in normal females, whereas the control androgenized females did not. Normal females did not exhibit any effects of antisense oligo treatment on sexual or locomotor behavior, but antisense oligo-treated normal females showed a trend (P = 0.09) toward disrupted estrous cyclicity and behaved differently in tests of open field behavior compared to controls. After killing, brains were processed for histology. Morphometric analysis of the sexually dimorphic nucleus of the preoptic area demonstrated a significantly smaller volume in antisense oligo-infused androgenized females compared with vehicle and scrambled oligo infused controls. The sexually dimorphic nucleus volume was smaller still in normal females infused with antisense oligo, consistent with estrogen receptor activation playing an active role in sexual differentiation of the female brain. These results demonstrate the effectiveness of antisense oligodeoxynucleotides in permanently altering a developmental process if administered during a critical period. PMID- 8344189 TI - Characterization of mannose 6-phosphate receptors (MPRs) from opossum liver: opossum cation-independent MPR binds insulin-like growth factor-II. AB - Bovine, human, and rat cation-independent mannose 6-phosphate receptors (CI-MPRs) are capable of binding both mannose 6-phosphate and insulin-like growth factor-II (IGF-II). However, the receptor isolated from either chicken or frog lacks the high affinity IGF-II-binding site. To determine whether CI-MPRs isolated from a species that is closely related to placental mammals can bind IGF-II, the MPRs were purified from a marsupial, the American opossum (Didelphis virginiana), by phosphomannan-Sepharose affinity chromatography and then tested for their ability to bind IGF-II. Opossum liver expressed both the CI-MPR and the cation-dependent MPR (CD-MPR). Both receptors contained Asn-linked oligosaccharides. In contrast to CD-MPRs isolated from other species, the opossum CD-MPR displayed heterogeneity with respect to the number of Asn-linked oligosaccharide chains it contains. The CI-MPR isolated from opossum liver, like the CI-MPR from bovine liver, bound iodinated human recombinant IGF-II. However, Scatchard analysis revealed that the opossum CI-MPR bound IGF-II with a lower affinity (Kd = 14.5 nM) than the bovine receptor (Kd = 0.2 nM). The addition of excess IGF-II, but not IGF-I or insulin, inhibited binding to [125I]IGF-II, indicating that the opossum CI-MPR exhibits specificity for IGF-II. These results suggest that the emergence of a high affinity IGF-II-binding site in the CI-MPR occurred in evolution before the divergence of marsupials and placental mammals from their last common ancestor. PMID- 8344190 TI - Androgen induction of steroid 5 alpha-reductase may be mediated via insulin-like growth factor-I. AB - The action of added insulin-like growth factor-I (IGF-I) and dihydrotestosterone (DHT) on steroid 5 alpha-reductase (5 alpha R) activity was studied using primary cultures of rat or human scrotal skin fibroblasts. Agents were added to cultured cells (2 x 10(5) cells) for 2 days, and enzyme activity was measured by the percent conversion of [3H] testosterone to DHT over a 4-h period in the absence of fetal calf serum or other growth factors. DHT, but not testosterone, at 10(-7) M significantly increased 5 alpha R activity (rat, 1.5 +/- 0.3% to 3.0 +/- 0.4%; human, 7.6 +/- 1.7% to 11.4 +/- 2.9%; P < 0.01). IGF-I (10(-9)-6.4 x 10(-9) M), but not IGF-II (10(-9)-10(-8) M) or insulin (10(-9)-10(-7) M), increased enzyme activity in a dose-related fashion [i.e. 1.5 +/- 0.5 to 10 +/- 2 in rat and 6.0 +/- 1.1 to 9.8 +/- 1.6% (P < 0.01) in human cells]. No change in cell numbers was observed in any experiment. Since the effect of IGF-I was about 100 times that of androgen, we studied the possibility that androgen induction of the enzyme activity could be via IGF-I production. Addition of a monoclonal antibody against IGF-I significantly reduced the effect of DHT, and simultaneous addition of a specific IGF-I receptor antibody blocked the expected induction of 5 alpha R activity (control, 4.9 +/- 0.5; DHT, 8.0 +/- 1.9; DHT plus IGF-I receptor antibody, 3.7 +/- 0.4%). No effect on 3 alpha-reduction of [3H]DHT to 3 alpha androstanediol was detected in separate experiments. These studies indicate that IGF-I may be an important regulator of skin 5 alpha R activity and, thus, may influence DHT formation. The previously known androgen induction of this peripheral steroidogenic enzyme may be via paracrine/autocrine production of an IGF-I-type growth factor. PMID- 8344191 TI - Maternal adrenalectomy alters the immune and endocrine functions of fetal alcohol exposed male offspring. AB - Exposure to ethanol in utero compromises the offspring's developing immune and endocrine systems. Persistent functional changes, particularly in T-cell dependent aspects of immunity and in hypothalamic-pituitary-adrenal activity, are commonly seen. The present study examined the degree to which fetal alcohol exposure (FAE) during development suppressed the lymphocyte proliferative response to Concanavalin-A (Con A). We also examined the effect of maternal adrenalectomy on the expression of glucocorticoid-regulated genes and the response to Con A in FAE offspring. Con A-stimulated lymphocyte proliferation was stably suppressed (between 28-46%) in FAE males compared to isocalorically pair fed offspring at 7, 21, 40, and 60 days of age. In contrast, lymphocyte proliferation in the immature or peripubertal FAE female was totally unaffected. In 60-day- old male rats, maternal adrenalectomy reversed the FAE-induced suppression of Con A-stimulated proliferation, but had no effect on lymphocyte proliferation. FAE increased anterior pituitary POMC (the precursor of ACTH) mRNA levels dramatically in males, and this increase was also reversed by maternal adrenalectomy. In both sexes, anterior pituitary glucocorticoid receptor mRNA levels were unaffected by prenatal alcohol exposure alone, but were significantly decreased in male and increased in female offspring of adrenalectomized dams ingesting alcohol. Furthermore, in male, but not female, offspring, hypothalamic levels of glucocorticoid receptor and CRF mRNA were increased significantly by FAE alone or in combination with maternal adrenalectomy. In female, but not male, offspring, maternal adrenalectomy with concomitant alcohol exposure increased anterior pituitary POMC mRNA levels compared to that in sham/pair-fed offspring. In summary, FAE induced a gender-specific impairment of Con A-stimulated lymphocyte proliferation. This deficit is present both before and after puberty, demonstrating its stability into adulthood. Furthermore, in males, maternal adrenalectomy reversed these FAE-induced deficits in T-cell function as well as the effect of FAE on anterior pituitary POMC expression. This supports the hypothesis that maternal adrenal hormones participate in the immunosuppressive "imprinting" of the FAE fetus and are, therefore, causally implicated in the sexually dimorphic T-cell dysfunction found in FAE offspring. PMID- 8344192 TI - Parastatin (porcine chromogranin A347-419), a novel chromogranin A-derived peptide, inhibits parathyroid cell secretion. AB - Chromogranin A (CgA), previously referred to as secretory protein-I, is a 50 kilodalton protein present in secretory granules of many endocrine and neuroendocrine cells. In the parathyroid it is present and cosecreted with PTH in response to hypocalcemia. CgA appears to be a precursor of bioactive peptides including pancreastatin, beta-granin, vasostatin, and chromostatin. The presence of several highly conserved pairs of basic amino acids, putative cleavage sites, in the CgA molecule suggests that other yet unidentified bioactive peptides might exist within the molecule. We tested this speculation by subjecting porcine parathyroid CgA to digestion by endoproteinase Lys-C. Resulting CgA-derived peptides were isolated by reverse-phase C18 HPLC and tested for their ability to affect low-Ca2+ stimulated secretion by porcine parathyroid cells. We characterized one peptide, which we named parastatin, that inhibited secretion of both PTH and CgA in a dose-dependent fashion over the range of 0.2-0.6 microM. Parastatin migrated as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent mol wt of 11,000. Edman degradation yielded the sequence L-S-F-R-A-P-A-Y-G-F-R-G-P-G-L corresponding to residues 347-361 of porcine CgA. Amino acid analysis of endoproteinase Lys-C and endoproteinase Asp-N generated fragments indicated that parastatin corresponds to residues 347-419 of CgA. A synthetic NH2-terminal fragment of rat parastatin corresponding to residues 1-19 was an inhibitory as intact porcine parastatin on parathyroid gland secretion. These results extend the concept that CgA is a precursor of biologically active peptides. PMID- 8344193 TI - Thyroid hormone regulation of RC3, a brain-specific gene encoding a protein kinase-C substrate. AB - RC3 is a brain-specific mRNA expressed in discrete neuronal groups of the forebrain that encodes a 78-amino acid protein, also called neurogranin, a calmodulin-binding, protein kinase-C substrate. Expression of RC3 mRNA was studied in normal and hypothyroid animals during the first month of life. Hypothyroid rats were produced by administration of methyl-mercapto-imidazol to the pregnant dams and subsequent surgical thyroidectomy on postnatal day 5 of the neonates. As studied by slot-blotting of total cerebrum poly(A)+ RNA, RC3 mRNA accumulates in normal brain from the fifth to seventh postnatal day, reaching maximal levels around days 10-12. RC3 mRNA accumulation in hypothyroid animals was blunted, and the maximal levels attained were about 30-50% of normal values. The effect of hypothyroidism on steady state mRNA levels was also observed by Northern blotting of RNA from cerebral cortex and striatum. As studied by immunoblotting using a polyclonal antibody, hypothyroidism also led to clear decreases in the amount of the RC3 protein in extracts from cerebral cortex, striatum, and hippocampus. A single administration of 10 micrograms T4 to hypothyroid rats on postnatal day 12 led to a steady increase in striatal RC3 mRNA from levels that were about 40% of normal to about 70% of normal at 16 h and 115% of normal at 48 h. In contrast to the effect on RC3, hypothyroidism did not affect developmental expression of the mRNA encoding GAP-43, another brain protein kinase-C substrate of axonal localization. RC3 is, thus, one of the few known neuronal genes whose expression is influenced by thyroid hormone in the brain. Thyroid hormone is required for an appropriate level of expression, not for the developmentally programmed timing of expression of the RC3 gene. PMID- 8344194 TI - Plasma membrane changes in the rat corpus luteum induced by oxygen radical generation. AB - The luteolytic mechanism was investigated in rat corpora lutea (CL). This study focused on the changes that occur in the plasma membrane. Previous experiments with rat luteal cells indicated that in vitro generation of superoxide radicals by xanthine oxidase disrupted LH-stimulated cAMP production and progesterone secretion similar to the effect of prostaglandin F2 alpha, the luteolytic hormone. In the present study, we observed that xanthine oxidase treatment of plasma membrane samples from CL caused a large decrease in fluidity, which also occurs during prostaglandin F2 alpha-induced luteolysis. This fluidity change was blocked by catalase, bromophenacyl bromide, an inhibitor of phospholipase-A activity, indomethacin, and free radical scavengers, and it was reversed by removal of FFA from the membrane. In addition, xanthine oxidase treatment caused phospholipid breakdown, formation of neutral lipids, a burst of inorganic peroxides, and a sustained rise in the level of lipid peroxides. These results indicate that free radical generation causes several changes that disrupt the plasma membrane of CL cells, and they raise the possibility that phospholipid breakdown could be involved in the mechanism that inhibits LH stimulation of steroidogenesis during luteolysis. PMID- 8344195 TI - Modulation of activin A action and specificity in the rat gonadotrope by protein kinase C. AB - This study was undertaken to assess the role of protein kinase C (PKC) in activin action in the rat pituitary. Pretreatment with 500 nM phorbol 12-myristate 13 acetate (PMA) for 22-24 h reduced subsequent FSH and LH release (percentage of total cellular FSH and LH released) in response to 100 nM PMA. This action persisted for 2 days after the pretreatment. Pretreatment with 500 nM 4 alpha phorbol 12,13-didecanoate (4 alpha PDD, a phorbol ester which does not activate PKC) did not affect cell responsiveness to 100 nM PMA. Both PKC-down-regulated cells and cells with a full complement of PKC responded similarly to 100 nM GnRH and 100 microM A23187 during this period. Incubation with 50 ng/ml activin A for 48 h significantly increased both FSH release and total FSH (extracellular plus intracellular) compared to corresponding basal values in PMA-pretreated cells, as well as in vehicle-or 4 alpha PDD-pretreated cells. Activin stimulation of basal FSH release and total FSH was significantly more potent in PMA-pretreated cells than in cells not pretreated with PMA. Activin did not alter basal LH release or total LH in vehicle- or 4 alpha PDD-pretreated cells but significantly increased both in PMA-pretreated cells. When PMA was present only during the initial 2 h of the 22- to 24-h pretreatment period at 50 nM, PKC was not down-regulated. In these cells, the potency of activin stimulation of basal FSH release was not affected, but stimulation of basal LH release by activin was still observed. These results suggest that PKC is not required for activin to stimulate FSH release but is involved as a modulator of potency and specificity of the activin action. PMID- 8344196 TI - Endothelin inhibits basal and stimulated release of prolactin by human decidual cells. AB - Recent studies have shown that the basal release of PRL from anterior pituitary cells is inhibited by endothelin-1 (ET-1) and ET-3. To determine whether ET also regulates the synthesis and release of PRL by decidual cells, we examined the effects of ET on the synthesis and release of PRL from an enriched fraction of human decidual cells prepared by isopycnic centrifugation of enzymatically dispersed term decidual tissue. Exposure of decidual cells to ET-1 (10(-7) M) for 96 h caused a progressive decrease in basal PRL synthesis and release beginning 24 h after exposure with half-maximal inhibition occurring at an ET-1 concentration of 5 x 10(-9) M. Between 72-96 h of culture, ET-1-exposed cells synthesized 37.2 +/- 2.7% (SEM) and released 32.3 +/- 1.3% less PRL than control cells (P < 0.01). ET-1-exposed cells incubated with [35S]methionine between 72-96 h also released less [35S] PRL than control cells. Sarafotoxin S6C, an ETB receptor agonist, also inhibited basal PRL release, whereas BQ-123, an ETA receptor antagonist, had no effect on basal or on ET-1-mediated inhibition of PRL release. ET-1 also markedly inhibited the stimulation of PRL synthesis and release in response to insulin and insulin-like growth factor-1 (IGF-1). Cells exposed to insulin (100 ng/ml) and IGF-1 (50 ng/ml) alone released 61.2 +/- 3.6% and 40.0 +/- 3.8% more PRL, respectively, than control cells between 72-96 h of exposure. However, cells exposed simultaneously to insulin and ET-1 (10(-7) M) released only 17.1 +/- 3.5% more PRL than control cells during the same time period, and cells exposed simultaneously to IGF-1 and ET-1 released only 4.1 +/- 1.8% more PRL than controls during the same time interval (P vs. insulin or IGF-1 alone < 0.001 in each instance). Both basal and insulin- and IGF-1-stimulated PRL release were also inhibited by the ET isotypes ET-2 and ET-3, and by the ET-1 precursor, big ET. Since macrophages and decidual cells synthesize ET, and decidual tissue contains specific receptors for ET, the inhibitory action of ET on basal and stimulated PRL release may result from an autocrine and/or paracrine effect and appears to be mediated through the ETB receptor. PMID- 8344197 TI - Prolactin induces maturation of glucose sensing mechanisms in cultured neonatal rat islets. AB - The effects of PRL treatment on insulin content and secretion, and 86Rb and 45Ca fluxes from neonatal rat islets maintained in culture for 7-9 days were studied. PRL treatment enhanced islet insulin content by 40% and enhanced early insulin secretion evoked by 16.7 mM glucose. Insulin release stimulated by oxotremorine M, a muscarinic agonist, in the presence of glucose (8.3 or 16.7 mM) was unchanged by PRL treatment. However, PRL treatment potentiated phorbol 12,13 dibutyrate-stimulated insulin secretion in the presence of the above glucose concentrations. PRL treatment potentiated the reduction in 86Rb efflux induced by glucose or tolbutamide and enhanced the increase in 86Rb efflux evoked by diazoxide. PRL treatment slightly potentiated the increment in 45Ca uptake induced by high concentrations of K+, but failed to affect the increment evoked by 16.7 mM glucose. Since glucose-induced 45Ca uptake was not affected by PRL, we suggest that the enhancement in first phase insulin secretion evoked by glucose in the PRL-treated islets occurs at a step in the secretory process that may involve protein kinase-C. These data further support observations that PRL treatment increases islet sensitivity to glucose. PMID- 8344198 TI - Expression and cellular localization of uterine side-chain cleavage cytochrome P450 messenger ribonucleic acid during early pregnancy in mice. AB - Very little is known about steroidogenic capacities in the uterus during the early stages of pregnancy in rodents. Cholesterol side-chain cleavage cytochrome P450 (P450scc) is the enzyme catalizing the first and key regulatory reaction controlling the production of steroid hormones. Using a cRNA probe, we made use of in situ hybridization analysis to evaluate the spatial and temporal patterns of P450scc mRNA expression in the mouse uterus until midgestation. Unexpectedly, we found that upon implantation on day 4.5, maternal cells of both decidua capsularis and decidua basalis expressed P450scc mRNA. Only later, and no earlier than day 6.5 of gestation, were high levels of P450scc mRNA also detected in the trophoblast giant cells surrounding the embryonal cavity. Analysis of pseudopregnant mice revealed that the induction of P450scc mRNA can be coupled to the decidual reaction evoked by intrauterine injection of mineral oil. These results, therefore, unambiguously confirmed the capacity of the decidualized cells of maternal origin to express P450scc mRNA and, thus, ruled out any direct role of the blastocyst involvement in P450scc induction. The dual localization of P450scc mRNA in maternal and trophoblast cells, expressing this cytochrome earlier than the previously suspected onset of uterine steroidogenesis, suggests an unexpected role for steroid hormones locally produced at the site of implantation and the surrounding milieu of the embryo during the first half of pregnancy. PMID- 8344199 TI - Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3',5'-monophosphate in MCF7 cells. AB - In MCF7 human breast cancer cells, the antiestrogens 4-hydroxy-tamoxifen and ICI 164,384 inhibit the mitogenic activity of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). These growth factors also stimulate the expression of cathepsin-D and pS2 genes. Therefore, we studied the effects of antiestrogens on growth factor induction of pS2 and cathepsin-D mRNA. The two antiestrogens strongly inhibited the transcriptional induction of pS2 by growth factors. On the contrary, estradiol and IGF-I or EGF had an additive effect on pS2 mRNA accumulation. Growth factor induction of cathepsin-D was also inhibited by ICI 164,384. By contrast, 4-hydroxytamoxifen had an agonist effect on cathepsin-D and an additive effect on IGF-I-induced mRNA. When 12-O tetradecanoylphorbol-13-acetate or 8-bromo-cAMP (8-Br-cAMP) was used instead of growth factors, similar effects of 4-hydroxytamoxifen and ICI 164,384 were obtained on pS2 (12-O-tetradecanoylphorbol-13-acetate and 8-Br-cAMP) and cathepsin-D (8-Br-cAMP) induction. A mechanism based on the classical competitive inhibition by antiestrogens of estrogen binding and action on the estrogen receptor was very unlikely, as 1) no antigrowth factor activity was obtained with R5020, which was a potent inhibitor of estrogen induction of pS2 and cathepsin-D mRNA; 2) in the Ishikawa endometrial cancer cell line, the cathepsin-D gene is unresponsive to estrogen, but was inhibited by antiestrogen after its induction by EGF or 8-Br-cAMP; and 3) the residual estrogen concentration in cells was too low to induce the expression of estrogen-specific genes. However, antiestrogens did not inhibit the expression of all genes induced by growth factors, as they were without effect on IGF-I induction of glyceraldehyde-3-phosphate dehydrogenase mRNA. These results demonstrate that antiestrogens can modulate the transcription of some growth factor-induced genes and strongly suggest that this effect is not due to interference with residual estrogens. PMID- 8344200 TI - The diurnal rhythm in vasopressin V1a receptor expression in the suprachiasmatic nucleus is not dependent on vasopressin. AB - The mammalian suprachiasmatic nucleus is the site of the circadian rhythm generator. The degrees of expression there of several neuropeptides, including vasopressin and vasoactive intestinal polypeptide, follow a diurnal rhythm. The vasopressin V1a receptor, whose activation results in phosphoinositol hydrolysis and mobilization of intracellular calcium, is expressed in this nucleus. This study used double simultaneous hybridization histochemistry to show that V1a receptor transcripts are present in both vasopressin and vasoactive intestinal polypeptide neurons and that their levels follow a diurnal rhythm. Furthermore, the expression of the V1a receptor is 12 h out of phase from that of vasopressin. However, the receptor's diurnal rhythm is still maintained in the vasopressin deficient Brattleboro rat, indicating that the V1a receptor's rhythm is independent of any vasopressin feedback. PMID- 8344201 TI - Characterization of glucose transporter isoforms in the adult and developing human eye. AB - The expression of glucose transporter isoforms (Glut 1, Glut 3, Glut 4, and Glut 5) in the human eye was investigated at various ages ranging between 8 weeks gestation (first trimester) and adult using Western blot and immunohistochemical analyses. Glut 1 and Glut 3 expression and cellular localization patterns were similar to those of human brain. Glut 1 (50-kilodalton protein) was expressed by epithelial cells (retinal pigmented epithelium, choroidal, iridial, and pars planus), which form the blood-eye barrier, retinal Mueller cells, the lens fiber cells, iridial microvascular endothelial cells, and to a lesser extent by the outer segments of the photoreceptor cells in the adult eye. This pattern was conserved throughout development and was evident as early as 8 weeks gestation. In addition, the endothelial cells of vitreous hyaloid vessels expressed Glut 1 at 8 weeks gestation. Glut 3 (50 to 55-kilodalton protein) immunoreactivity was observed only in the adult inner synaptic layer of the retina. Neither Glut 4 nor Glut 5 was expressed in any occular tissue at any age examined. These results suggest that Glut 1 is the main glucose transporter of the human eye and that it is ontogenically conserved. In contrast, Glut 3 is associated with selective neuronal processes, and its expression is developmentally altered. PMID- 8344202 TI - Existence of activin-A in A- and D-cells of rat pancreatic islet. AB - Activin-A, a member of the transforming growth factor-beta supergene family, stimulates insulin secretion in rat pancreatic islets and causes glycogenolysis in isolated rat hepatocytes. These observations prompted us to determine whether activin-A existed in rat pancreas by using an immunocytochemical method. Cells in pancreatic islets were stained by antibody against activin-A, whereas no immunoreactivity was observed in exocrine pancreas. Cells localized in the mantle of the islets were densely stained by the antibody. Immunoelectron microscopic study showed that activin-A existed in secretory granules in both A- and D-cells. Furthermore, studies using a double labeling method revealed that activin-A coexisted with glucagon in secretory granules in A-cells and with somatostatin in D-cells. Antibody against inhibin-A weakly stained cells in both the core and mantle of the islets only when the rat was pretreated with colchicine. Subtypes of activin subunit in islets were identified to be beta A by a reverse transcription-polymerase chain reaction method. In addition, mRNA for inhibin alpha-subunit was expressed in islets. However, mRNA for these inhibin subunits was not detected in exocrine pancreas. To further examine the action of activin-A on insulin secretion, we examined the effect of activin-A in a flow-through perifusion system. Activin-A induced a biphasic insulin secretory response in the presence of 2.8 mM glucose, and a low concentration of activin-A, which does not stimulate insulin secretion by itself, markedly enhanced glucose-mediated insulin secretion at concentrations above 2.8 mM glucose. Inhibin-A did not affect insulin secretion. These results suggest the existence of activin-A in A- and D cells of rat pancreatic islets and raise the possibility that activin-A acts as a physiological regulator of carbohydrate metabolism. PMID- 8344203 TI - Processing of mutated proinsulin with tetrabasic cleavage sites to mature insulin reflects the expression of furin in nonendocrine cell lines. AB - Furin is a mammalian propeptide-processing endoprotease in nonendocrine cells and has been demonstrated to be present in virtually all nonendocrine cells, including fibroblasts, epithelial cells, and hepatocytes. Furin cleaves the concensus processing site -Arg-4-X-3-Lys/Arg-2-Arg-1 decreases X+1-. Some subunit containing precursor proteins, including an insulin receptor precursor, possess an additional basic residue at position -3, thus forming a tetrabasic processing site. This implies that a tetrabasic processing site must be easily cleavable in nonendocrine cells. We created a mutant proinsulin DNA with a peptide structure comprised of B- and A-chains linked to the C-peptide by a pair of tetrabasic residues, in the following order: B-chain-Arg-Arg-Lys-Arg-C peptide-Arg-Arg-Lys Arg-A-chain. The native proinsulin structure was B-chain-Arg-Arg-C-peptide-Lys Arg-A-chain. Both the native and mutant proinsulins were expressed in the following four cell lines: a monkey kidney-derived cell line (COS-7), a Chinese hamster ovary-derived cell line (CHO), a human liver cancer-derived cell line (HepG2), and a mouse fibroblast-like cell line (NIH3T3). We used these cell lines because they contain different quantities of furin mRNA, ranking as follows: NIH3T3 > HepG2 > COS > CHO. When mutant insulin was expressed in these cells, the conversion of proinsulin to mature insulin was approximately 85% in NIH3T3, 70% in HepG2, 60% in COS, and 50% in CHO. The conversion correlated well with the furin expression in each cell line as measured by the density of its Northern blot band. Moreover, in CHO, the cell line with the lowest furin expression, coexpression of mutant proinsulin with furin resulted in complete conversion of proinsulin to mature insulin. PMID- 8344204 TI - A developmentally regulated form of insulin-like growth factor receptor beta subunit in C2 myoblasts exhibiting altered requirements for differentiation. AB - Ligand-dependent autophosphorylation and immunoprecipitation have been used to distinguish insulin and insulin-like growth factor-I (IGF-I) receptor beta subunits in the permissive and inducible subclones of the C2 myoblast cell line. Permissive myoblasts differentiate spontaneously, whereas myoblasts of the inducible subclone require exogenous IGFs to undergo terminal differentiation. Permissive myoblasts contain beta-subunits of 95 and 101 kilodalton (kDa) mol wt. The 95-kDa subunits are immunoprecipitated with antipeptide antibodies directed against tyrosine kinase (AbP2), juxtamembrane (AbP4), and carboxy-terminal (AbP5) domains of the insulin receptor and insulin receptor monoclonal antibody 29B4. The tryptic phosphopeptide map of the 95-kDa band suggests that it contains both insulin and IGF-I receptor beta-subunits. The 101-kDa subunit is immunoprecipitated by AbP2, AbP4, and AbP5, because it forms a hybrid complex with the 95-kDa protein, but it does not react directly with AbP4, AbP5, or antibody 29B4. Phosphorylation of the 101-kDa subunit is more responsive to IGF-I than to IGF-II or insulin, indicating that it is a second IGF-I receptor beta subunit. Inducible myoblasts exhibit a single major beta-subunit of 106 kDa mol wt. Its immunoreactivity and phosphopeptide map are virtually identical to those of the 101-kDa IGF-I receptor beta-subunit from permissive cells. However, unlike the 101-kDa beta-subunit, phosphorylation of the 106-kDa protein appears to be more responsive to IGF-II than to either IGF-I or insulin. It is lost upon differentiation of myoblasts into myotubes concomittant with the appearance of 95 and 101-kDa beta-subunits. These data demonstrate 1) an alpha 2 beta 2 IGF receptor that has high sensitivity for IGF-II in inducible, but not in permissive, myoblasts; 2) the beta-subunit of this receptor exhibits different migration in sodium dodecyl sulfate-polyacrylamide gels from either of those found in permissive cells; and 3) expression of this beta-subunit is developmentally regulated. This suggests that the inducible cell beta-subunit is a component of a stage-specific alpha 2 beta 2 IGF receptor subtype that functions as an IGF-II receptor. PMID- 8344205 TI - Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic stimulation of prolactin secretion via 5-HT1c/2 receptors. AB - These studies examined the hypothalamic site and receptor subtype mediating the serotonergic (5-HT) control of PRL secretion in conscious male rats. Initially, we characterized the pharmacology of the 5-HT releaser and 5-HT agonists that increase PRL release. Subsequently, we performed lesion experiments to locate the 5-HT receptors involved in PRL secretion. p-Chloroamphetamine, a 5-HT releaser, is postulated to enter serotonergic nerve terminals through the 5-HT uptake mechanism, which can be inhibited by fluoxetine. p-Chloroamphetamine (8 mg/kg, ip) increased the plasma PRL concentration approximately 6-fold. The 5-HT uptake inhibitor fluoxetine almost completely prevented this increase, demonstrating that p-chloroamphetamine increases PRL release via a serotonergic mechanism. The 5-HT1C/5-HT2 agonist +(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl (ip) produced a strong (30-fold) dose-dependent elevation of plasma PRL, which was virtually eliminated by 0.1 mg/kg (sc) ritanserin, a 5-HT1C/5-HT2 antagonist. +( )-1-(2,5-Dimethoxy-4-iodophenyl)2-aminopropane HCl injected intracerebroventricularly (icv) in doses below those that were peripherally effective also produced a significant (8-fold) increase in PRL secretion that was again attenuated by icv pretreatment with ritanserin (2 micrograms/kg). RU 24969 (5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]1H-indole) was reported to act as both a 5-HT releaser and a direct postsynaptic 5-HT agonist. To test whether RU 24969 releases 5-HT to increase PRL secretion, we depleted 5-HT stores with the 5 HT synthesis inhibitor p-chlorophenylalanine. The ability of RU 24969 (0.5, 1, 5, and 10 mg/kg, ip) to elevate PRL secretion was not inhibited by pretreatment with p-chlorophenylalanine, suggesting that RU 24969 stimulates PRL secretion only through activation of postsynaptic 5-HT receptors. To test whether RU 24969 acts centrally, it was injected either icv, through chronic icv cannulae, or peripherally (ip). RU 24969 injected icv significantly stimulated PRL secretion (11-fold) at doses 500-fold lower than the peripherally effective doses (10 micrograms/kg vs. 5 mg/kg), suggesting a role for central 5-HT receptors in the regulation of PRL secretion. In addition, rats pretreated with the 5-HT1C/5-HT2 antagonist LY53857 (icv) significantly inhibited the PRL response if RU 24969 was injected ip, but not icv. The results of these experiments suggest that 5-HT1C or 5-HT2 receptors in the brain participate in the serotonergic stimulation of PRL secretion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8344206 TI - ZR-75-1 breast cancer cells generate nonconjugated steroids from low density lipoprotein-incorporated lipoidal dehydroepiandrosterone. AB - Fatty acid esters of dehydroepiandrosterone (DHEA-FA) are present in the circulation, although no physiological function has yet been attributed to these metabolites. They are formed directly in serum and are predominantly localized in association with lipoproteins. The objective of this study was to determine the capacity of these lipoprotein-incorporated DHEA metabolites to generate nonconjugated steroids after incubation with cells in culture. A method for studying DHEA-FA using a radiolabeling technique that marks human low density lipoproteins (LDL) with tritiated DHEA-FA was elaborated. Analysis of the fatty acid composition of tritiated DHEA-FA-labeled LDL ([3H] DHEA-FA-LDL) indicated the prevalence of DHEA-linoleate/palmitoleate and DHEA-oleate. Incubation of [3H]DHEA-FA-LDL with ZR-75-1 breast cancer cells produced a time-dependent increase in labeled nonconjugated steroids in the cell culture medium, whereas the levels of tritiated DHEA-FA decreased. Lipoidal radioactivity in cells increased with time, but nonconjugated radioactivity associated with the cells showed no such increase. HPLC analysis of the culture medium indicated the presence of DHEA and androst-5-ene-3 beta,17 beta-diol. The endogenous levels of lipoidal DHEA were also determined in human plasma and its lipoprotein components to reveal that these metabolites circulate naturally in the range of 6.5 +/- 0.4 nM. Approximately 90% of this concentration was associated with the lipoprotein components, namely among the LDL and high density lipoprotein fractions. These results suggest that lipoidal DHEA may indeed act as a substrate for potent steroid formation after their entry into steroid target cells. PMID- 8344207 TI - Coordinate induction and activation of metalloproteinase and ascorbate depletion in structural luteolysis. AB - Structural luteolysis was found decades ago to be induced by PRL in the hypophysectomized rat, but the mechanisms of this process are unknown. To gain information on mechanisms of luteal involution, we developed an animal model that circumvented complex surgery and provided ample tissue for analyses. Gonadotropin synchronized ovulation and luteinization were induced in immature rats, followed by treatment with ergot alkaloid and PRL. PRL-induced structural luteolysis, as shown by loss of luteal weight, protein, and DNA after pretreatment with ergot alkaloid, was evident after 36 h. Ascorbic acid depletion was rapid, severe, and lasting in luteal tissue during structural luteolysis, but lipid peroxidation or depletion of vitamin E was not evident. PRL treatment of animals with functional corpora lutea did not induce luteal involution. Significantly, after natural functional luteolysis occurred, PRL was highly effective in inducing structural luteolysis. Thus, either natural or ergot-induced functional luteolysis permitted the luteolytic expression of PRL. A greater depletion of protein than DNA was seen during PRL-induced structural luteolysis and was associated with a significant increase in neutral caseinase activity in luteal extracts. Caseinase activity was markedly reduced by calcium chelators and profoundly inhibited by the chelator orthophenanthroline; only slightly reduced activity was seen with serine, aspartate, or cysteine proteinase inhibitors. These findings implicate metalloproteinase (MMP) as the relevant caseinase that was increased during structural luteolysis. The major proteinase identified by zymography had apparent sizes of 72 and 66 kilodaltons (kDa), and slight but detectable activity was also seen at 92 and 84 kDa. Organomercurial treatment caused a major shift of the 72 kDa band to 66 kDa and the 92-kDa band to 84 kDa, confirming MMP-2 and MMP-9 by activation of latent activity of each MMP, respectively. Structural luteolysis caused a significant increase in the activated 66-kDa form and the latent 72-kDa form of MMP-2, which occurred before a loss of luteal weight or protein. As MMP-2 degrades collagen (type IV) in basement membranes, we conclude that an early event in PRL-induced structural luteolysis is the degradation of extracellular matrix. This conclusion is further emphasized by the marked and lasting depletion of ascorbic acid, a vitamin long known to serve an essential role in collagen synthesis. PMID- 8344208 TI - Noncoordinated expression of luteal cell messenger ribonucleic acids during human chorionic gonadotropin stimulation of the primate corpus luteum. AB - In nonfertile cycles, the absolute steroidogenic capacity of the primate corpus luteum, as reflected in the expression of messenger RNA (mRNA) for the progesterone biosynthetic enzymes cytochrome P450 cholesterol side-chain cleavage (P450SCC) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), progressively declines until luteal regression. Despite this progressive loss in luteal cell function, the elaboration of CG by the implanted blastocyst is able to prolong the functional lifespan of the corpus luteum. It was the purpose of this study to investigate the relationship between aging of the primate corpus luteum and the cellular mechanisms by which the decline in luteal cell function is arrested by CG. Corpora lutea were obtained from cynomolgus monkeys on days 11 or 16 of the luteal phase after a 7-day treatment period with increasing doses of human CG (hCG) given intramuscularly beginning on days 5 or 10. Corpora lutea were also obtained from control animals on days 5, 10, 11, and 16 of the luteal phase. Human CG treatment significantly (P < 0.05) elevated both serum progesterone and estradiol levels throughout the treatment period; however, progesterone production in animals treated with hCG late in the luteal phase (days 10-16) steadily declined after the third treatment day. Expression of mRNA for P450SCC and 3 beta-HSD was markedly stimulated (P < 0.05) by hCG treatment early in the luteal phase. However, 3 beta-HSD message levels in corpora lutea from animals treated with hCG on days 10-16 were not different from those of day-16 control corpora lutea, whereas P450SCC mRNA was only minimally stimulated. There was a dramatic (P < 0.05) increase in mRNA levels for the aromatase enzyme and low density lipoprotein receptor in animals given hCG in both the early and the late luteal phase. In conclusion, there appears to be a differential responsiveness of the primate corpus luteum to hCG stimulation dependent upon luteal age. The loss in responsiveness to hCG in terms of maintenance of mRNA levels is reflective of the inability of the late luteal phase corpus luteum for continued progesterone biosynthesis in the face of heightened luteotropic stimulation. PMID- 8344209 TI - Modification of insulin resistance by diazoxide in obese Zucker rats. AB - Hyperinsulinism, insulin resistance, and decreased number of insulin receptors are characteristic of obesity in both humans and experimental animals. To assess the role of insulin in developing obesity, diazoxide (DZ), an inhibitor of glucose-stimulated insulin secretion, was administered for 8 weeks to 7-week-old female Zucker rats in two concentrations, 50 mg/kg.day (LD-DZ), and 100 mg/kg.day (HD-DZ). The obese and lean rats were divided into three subgroups: diazoxide (DZ), pair-fed (PF), and control (C) groups (n = 6 rats/subgroup-genotype). Diazoxide-treated obese and lean animals showed significantly lower postabsorptive plasma insulin concentrations (P < 0.005) than their respective obese and lean PF and C subgroups. HD-DZ obese rats consumed more calories (P < 0.001), yet gained less weight (P < 0.05) than PF and C rats. The plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests in HD-DZ obese rats were significantly lower than those in PF and C rats (P < 0.01) despite a decrease in their plasma insulin concentrations (P < 0.01), whereas HD DZ lean rats displayed a diabetic response (P < 0.01). The adipocyte-specific insulin receptor binding was dose-dependently increased in both lean and obese DZ animals (P < 0.01). DZ had a dual effect on insulin metabolism; it decreased insulin secretion and increased insulin receptor binding. This dual effect was associated with improved glucose tolerance and a decrease in weight gain in obese rats. PMID- 8344210 TI - Structure-function requirements of parathyroid hormone for stimulation of 1,25 dihydroxyvitamin D3 production by rat renal proximal tubules. AB - PTH stimulates synthesis and secretion of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in renal proximal tubule cells through activation of the protein kinase-A (PKA) or the protein kinase-C (PKC) signaling pathway. The relative contribution of the two transducing systems was explored using PTH fragments with selective activation of either PKA or PKC. Rat renal proximal tubules were isolated by Percoll centrifugation, and PKA and PKC activities were measured after treatment with synthetic fragments and analogs of PTH. Rat PTH-(1-34), [Nle8,Nle15,Tyr34]bovine PTH-(3-34), and human PTH-(13-34) increased PKC activity in a dose-dependent manner. All fragments tested stimulated PKC at physiological concentrations (10(-11)-10(-10) M). Rat PTH-(1-34) (10(-7) M) increased PKA activity 4.5-fold, but other fragments failed to stimulate PKA between 10(-12) 10(-6) M. Human PTH-(28-34) stimulation of PKC was variable from experiment to experiment. All four PTH fragments tested increased 1,25-(OH)2D3 secretion by perifused renal proximal tubules at the lowest concentrations that stimulated PKC activity. The adenylate cyclase inhibitor 2',5'-dideoxyadenosine (10(-4) M) reduced PTH-(1-34)-stimulated PKA activity by 60%, but failed to block the rise in 1,25-(OH)2D3 secretion. The results of these studies demonstrate that PTH fragments that contain the PKC translocating domain stimulate 1,25-(OH)2D3 secretion, whereas elimination of the PKA activation domain does not alter the potency of the analogs' 1,25-(OH)2D3-stimulating activity. These results support the concept that PKC translocation may be required for PTH stimulation of 1,25 (OH)2D3 secretion. PMID- 8344211 TI - Interactions of transforming growth factor-alpha and -beta and luteinizing hormone in the regulation of plasminogen activator activity in avian granulosa cells during follicular development. AB - This study examined the influence of transforming growth factor-alpha (TGF alpha), TGF beta, and LH on progesterone (P4) secretion and plasminogen activator (PA) activity in cultured avian granulosa cells from the first (F1), third (F3), and fifth and sixth (F5-6) preovulatory follicles during a 21-h incubation period. PA activity in the cell (PAc) and the medium (PAm) fractions was measured by fibrinolysis and fibrin overlay methods. P4 was determined by RIA. Basal PAc and PAm activities were highest in cell cultures from the less mature (F5-6) follicles and decreased as follicles matured to the F1 stage of development. PAc activity was greater than PAm activity regardless of the stage of follicular maturation. TGF alpha (0.1-10 ng/ml) increased PA activity in cultures of granulosa cells from F1, F3, and F5-6 follicles in a concentration-dependent manner. TGF alpha-induced PAc and PAm activities were observed by 6 and 15 h of incubation, respectively, and increased rapidly between 15-21 h. LH (100 ng/ml) attenuated TGF alpha-induced PA activity by 15 h in cultures of granulosa cells from F1 and F3, but not F5-6, follicles. Basal PA activities were unaffected by the gonadotropin. TGF beta (2-100 ng/ml) stimulated PAc activity in a dose dependent manner only in cultures of granulosa cells from F5-6 follicles and significantly enhanced TGF alpha-induced PAc and PAm activities in cell cultures from F3 and F5-6, but not F1, follicles. Basal and growth factor-induced PAc and PAm activities corresponded to a mol wt of about 35 kDa, a value consistent with that of the low mol wt uPA species. TGF alpha and TGF beta, alone or in combination, had no effect on basal P4 secretion at all stages of follicular development. TGF alpha, however, decreased LH-induced P4 secretion in F1 and F3 cultures. These results demonstrate a tightly controlled interaction of TGF alpha, TGF beta, and LH in regulating PA activity and P4 secretion during follicular development in the domestic hen. PMID- 8344212 TI - The steroid antagonist RU486 exerts different effects on the glucocorticoid and progesterone receptors. AB - To determine whether the steroid antagonist RU486 mediates its antiglucocorticoid and antiprogestin activities by the same or different receptor mechanisms, a direct comparison of RU486 interaction with glucocorticoid (GR) and progesterone (PR) receptors was made. The effects of RU486 on transformation of GR and PR 8 10S complexes in the intact cell and in vitro were analyzed by sucrose density gradient centrifugation, and the in vitro stability of receptor-heat shock protein-90 interactions was analyzed by coimmunoprecipitation. Compared to agonist, RU486 binding produced a reduction in the amount of GR converted from 8S to 4S and stabilized the GR-heat shock protein-90 complex. By contrast, PR-RU486 complexes were transformed both in vitro and in the intact cell to the same extent as receptor-agonist complexes. PR-RU486 complexes sedimented at 5-6S, whereas PR-R5020, GR-RU486, and GR-agonist complexes sedimented at 4S. The portion of GR that undergoes nuclear transformation when bound to RU486 was examined for binding to the glucocorticoid-progesterone response element of the mouse mammary tumor virus by an immunoprecipitation assay. The nuclear transformed GR-RU486 complex bound the glucocorticoid-progesterone response element with the same affinity as the nuclear-transformed GR-triamcinolone acetonide complex. The electrophoretic mobilities of GR-RU486 complexes and GR agonist complexes were the same, as determined by gel retardation assay. These results suggest that RU486 exerts its antiglucocorticoid activity at two levels of receptor action: prevention of complete GR transformation and alteration of a step subsequent to GR-DNA binding. As an antiprogestin, RU486 action is exerted predominantly at a post-DNA-binding step. PMID- 8344213 TI - Role of neuropeptide-Y in episodic luteinizing hormone release in ovariectomized rats: an excitatory component and opioid involvement. AB - We tested the hypothesis that hypothalamic neuropeptide-Y (NPY) is an excitatory signal in the episodic secretion of LH in ovariectomized (ovx) rats and that the suppression of LH secretion that consistently follows intracerebroventricular administration of NPY is due to concurrent release of opioids or CRH, both previously shown to readily inhibit LH release. In the first experiment, ovx rats received continuous intraventricular infusion of either serum containing NPY antibodies (NPY-Ab) or normal rabbit serum (control) at dilutions of 1:5 or 1:1. NPY-Ab infusion at a 1:5 dilution significantly decreased mean plasma LH levels and LH pulse amplitude without affecting LH pulse frequency over a 3-h period of observation. However, infusion of relatively more concentrated NPY-Ab (1:1) markedly decreased not only mean plasma LH levels and LH pulse amplitude, but also the frequency of LH episodes. In the next experiment, we observed that intraventricular administration of NPY (0.2 nmol) suppressed LH release for 60 min. However, blockade of opiate receptors with iv infusion of naloxone (2 mg/h) before and after NPY injection completely counteracted the NPY-induced inhibition of LH release. On the other hand, prior blockade of the CRH receptors with alpha helical CRH-(9-41) (25 or 100 micrograms/rat) was ineffective in reversing the inhibitory LH response of NPY (0.125 nmol). These results together with our previous demonstration of morphological communication between NPY and beta endorphin neurons, show that suppression of LH by exogenous NPY in ovx rats may result from concurrent stimulation of opioids, primarily beta-endorphin. However, diminution of all parameters of episodic LH secretion by NPY-Ab affirms the notion that the NPY network is a physiologically important excitatory component of the hypothalamic pulse generator circuitry that regulates episodic LH secretion in rats. PMID- 8344214 TI - High neonatal triiodothyronine levels reduce the period of Sertoli cell proliferation and accelerate tubular lumen formation in the rat testis, and increase serum inhibin levels. AB - T3 was injected daily in newborn rats from birth to 16 days of age. Control rats received daily injections of vehicle during the same period. The proliferative activity of the Sertoli cells was studied by means of bromodeoxyuridine incorporation, and tubular lumen formation and nuclear size were taken as markers of Sertoli cell differentiation. T3 treatment strongly reduced the proliferative activity of Sertoli cells from day 7 on, and on day 12, proliferation of Sertoli cells had ceased, while in control rats proliferating Sertoli cells were observed up to day 16. As a result of the reduced Sertoli cell proliferation, the final Sertoli cell number per testis at 23 days of age was reduced by 50% from 38 +/- 1 x 10(6) in control rats to 19 +/- 1 x 10(6) in T3-treated rats. Lumen formation in seminiferous tubules of T3-treated rats began at 12 days of age, while in controls lumen formation was first observed at 16 days. The area of the Sertoli cell nuclei was somewhat larger in T3-treated rats on day 16, but not at any other age examined. Body and testis weights in adult rats at 100 days of age were reduced by 46% and 48% of control values, respectively. The high neonatal T3 levels reduced serum levels of TSH on days 7 and 9, but not at any other age examined. FSH levels were reduced in T3-injected rats on days 5 and 7 and increased on day 23, after cessation of treatment. Immunoreactive inhibin-alpha levels were increased on days 5-9 and reduced on days 16 and 23. These findings indicate that T3 stimulates the production of immunoreactive inhibin by Sertoli cells, but also of bioactive inhibin, as indicated by the reduced FSH levels. It is concluded that the levels of thyroid hormones early in life are important for the terminal differentiation of Sertoli cells and, therefore, for determining adult testis size. The data indicate that this might be a direct effect of T3 on Sertoli cells. PMID- 8344215 TI - Hormonal regulation, localization, and functional activity of the progesterone receptor in granulosa cells of rat preovulatory follicles. AB - Progesterone has been implicated to play a critical role in mediating LH induction of ovulation and possibly luteinization. The present study was undertaken to determine the effects of various agonists (LH, FSH, forskolin, and GnRH) known to stimulate ovulation on their abilities to induce progesterone receptor (PR) mRNA and protein in rat preovulatory follicles and in cultured rat granulosa cells exhibiting a preovulatory phenotype. In cultured granulosa cells, PR mRNA was induced by LH in a dose- and time-dependent manner. Transcripts of approximately 11.0, 7.2, 6.8, 6.2, 3.4, and 3.1 kilobases in size were induced by ovulatory (500 ng/ml), but not low (50 ng/ml), concentrations of LH and FSH as well as by forskolin (10 microM), GnRH (1 microM), and phorbol 12-myristate 13 acetate (200 nM). Two forms (A and B) of PR protein were also induced in an agonist- and time-dependent manner, with the shorter form A (mol wt, 83,000 85,000) appearing in greater abundance than the longer form B (mol wt, 115,000). Indirect immunofluorescent analyses verified nuclear localization of the induced receptor. Forskolin and progesterone, but not progesterone alone, were able to activate a glucocorticoid (progesterone) response element-E1b-chloramphenicol acetyltransferase reporter construct (12-fold) after transfection into cultured granulosa cells. The antiprogestins RU486 and ZK98299 did not inhibit induction of PR mRNA and protein, but effectively blocked agonist activation of glucocorticoid response element2-E1b-chloramphenicol acetyltransferase, as well as LH stimulation of luteinization in vitro. These results provide direct evidence that agonists stimulating diverse intracellular pathways can induce PR in granulosa cells, that progesterone plays a functional role in the luteinization process triggered by the LH surge, and that the effects are mediated at least in part by induction of PR. PMID- 8344216 TI - Mechanisms of regulation of ovarian sterol metabolism by insulin-like growth factor type II: in vitro studies with swine granulosa cells. AB - The present studies were designed to investigate the nature of the actions of insulin-like growth factor-II (IGF-II) on granulosa cell steroidogenesis and assess the potential facilitative interactions between IGF-II and other major regulators of ovarian sterol metabolism, viz. estrogen, FSH, and low density lipoprotein (LDL). In serum-free first passage monolayer cultures of swine granulosa cells, human recombinant IGF-II stimulated progesterone production with a half-maximally effective concentration of 4.6 +/- 1.2 ng/ml (0.61 +/- 0.16 nM) between 0-48 h of culture and 27 +/- 5.7 ng/ml (3.6 +/- 0.76 nM) between 48-96 h. Maximal progesterone accumulation increased 12-fold over that in untreated cultures (48-96 h). Over the latter interval, IGF-I stimulated progesterone production approximately 10-fold, with a significantly lower ED50 of 6.1 +/- 0.70 ng/ml (0.78 +/- 0.09 nM; P < 0.01 vs. IGF-II effect). IGF-II (100 ng/ml) enhanced progesterone biosynthesis approximately 2-fold in the presence of 25 hydroxycholesterol, suggesting that IGF-II increases the effective activity of the mitochondrial cholesterol side-chain cleavage enzyme. IGF-II (100 ng/ml) augmented human LDL-promoted progesterone production approximately 18-fold between 0-48 h of culture and approximately 6-fold between 48-96 h. In addition, IGF-II showed time-dependent stimulatory effects on the rates of [125I]iodo-LDL internalization, and the amounts of cell-associated and degraded lipoprotein. IGF II increased by approximately 10-fold the number of specific high affinity LDL receptors on granulosa cells, with no apparent change in their binding affinity, as assessed in equilibrium competition studies. Coadministration of IGF-II and FSH (100 ng/ml) or estradiol (E2; 1 microgram/ml) for 2 days increased progesterone production synergistically. Cotreatment with FSH or E2 for 4 days decreased the ED50 of IGF-II's stimulation of progesterone accumulation by 61% and 50%, respectively (P < 0.01). Synergistic interactions also existed between IGF-II and 8-bromo-cAMP, which indicates that IGF-II can act in part at cellular loci distal to cAMP generation. Northern blot analysis of total RNA isolated from granulosa cells treated with IGF-II (100 ng/ml), FSH (100 ng/ml), or IGF-II plus FSH for 2 days revealed 5-, 7-, or 8-fold increases, respectively, in the amount of cytochrome P450 cholesterol side-chain cleavage enzyme mRNA. The same treatments produced 6-fold increases in the level of LDL receptor mRNA, as determined by solution hybridization/RNase protection assays.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8344217 TI - A cryptic peptide from the preprothyrotropin-releasing hormone precursor stimulates thyrotropin gene expression. AB - The precursor peptide of TRH (prepro-TRH) contains five copes of pro-TRH linked by other peptide sequences. These peptides are coprocessed with TRH in the median eminence of the hypothalamus and released into the portal circulation, rendering this family of peptides available to act at the level of the anterior pituitary. Therefore, we tested the potential bioactivity of one cryptic peptide, prepro-TRH amino acids 160-169 [prepro-TRH-(160-169)], in a TRH-responsive pituitary cell line (GH3). In a heterologous TSH expression assay, we found that prepro-TRH-(160 169) stimulated TSH beta gene promoter activity in a time- and dose-dependent manner; moreover, the effect of prepro-TRH-(160-169) was more rapid and of greater magnitude than that of TRH on TSH beta-directed chloramphenicol acetyltransferase synthesis. In the same cells, we found that prepro-TRH-(160 169) stimulated PRL synthesis and secretion, but the effect was similar in magnitude and duration to that of TRH. The effect of prepro-TRH-(160-169) appears to be additive to that of TRH, suggesting that prepro-TRH-(160-169) may act through a mechanism separate from that of TRH. Thus, prepro-TRH-(160-169) has potent endocrinological effects at the level of the genome. PMID- 8344218 TI - Endotoxin-induced corticotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is mediated centrally by interleukin-1. AB - In the acute phase of bacterial infection, a variety of cytokines, including interleukin-1 (IL-1), are elicited by bacterial endotoxin in both the periphery and the central nervous system. Bacterial endotoxin has been previously reported to profoundly activate the hypothalamic-pituitary-adrenal axis, resulting in elevated glucocorticoid secretion that may serve an important role as part of the inhibitory feedback mechanisms on the activated immune system. To determine whether IL-1 acts within the brain to mediate endotoxin-induced CRH gene expression in the hypothalamic paraventricular nucleus (PVN), we studied the effect of administering the human IL-1 receptor antagonist (IL-1ra) into the brain, a competitive inhibitor of IL-1, on CRH gene expression in the PVN after systemic lipopolysaccharide (LPS) treatment. Eight hours after the ip administration of LPS, the paraventricular CRH mRNA content was elevated 3-to 4 fold (P < 0.01) compared to the control value, and this elevation could be completely abolished by central IL-1ra pretreatment (P < 0.05 compared to LPS treated group; P > 0.05 compared to controls). In contrast, systemic IL-1ra administration did not inhibit endotoxin-induced CRH gene expression in the PVN. These studies demonstrate that LPS stimulates hypothalamic CRH by a mechanism that involves the action of IL-1 within the central nervous system and may proceed independently of peripheral actions of IL-1 circulating in the bloodstream. PMID- 8344220 TI - Oxytocin enhances myoepithelial cell differentiation and proliferation in the mouse mammary gland. AB - Using immunocytochemistry and electron microscopy, we demonstrate that oxytocin (OT) exerts a trophic effect on its target myoepithelial cells in the mammary gland. In vitro, in organotypic cultures of mouse mammary gland, we examined proliferation and differentiation of the different cell types induced by OT added to the medium. In vivo, we studied the effect of OT on the structure and cell composition of developing glands. Uptake of 5-bromo-2'-deoxyuridine was used as proliferation marker, while antibodies to smooth muscle alpha-actin (specific for myoepithelial cells) and keratin (MoAb AE1; selective for epithelial cells) were used to identify differentiated cell types. By electron microscopy, we studied structural modifications induced by OT on the extreme projections of the developing gland (sc end buds). The results indicate that OT induces myoepithelial cell differentiation and proliferation, enhancing the effect of mammotrophic hormones in nonlactating mouse mammary gland. A less marked effect was observed in luminal epithelial cells. No significant effect of OT alone was detected in cultured glands from unprimed animals. PMID- 8344219 TI - Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth. AB - In the uterus, estrogen causes a rapid increase in microvascular permeability, followed later by growth of the endometrium, including the richly vascular stroma. Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF or VEG/PF) is an angiogenic protein that is not only a specific mitogen for endothelial cells, but also a potent stimulator of microvascular permeability. Because of these properties, it seems likely that VEG/PF might mediate estrogen induced increases in uterine vascular permeability and blood vessel growth. Therefore, we determined whether the gene for VEG/PF is expressed in the rat uterus and if mRNA abundance is regulated by steroid hormones, using reverse transcription-polymerase chain reaction. The VEG/PF gene is alternatively spliced and gives rise to three transcripts coding for proteins of 188, 164, and 120 amino acids, which, in turn, form the active dimeric factors. Transcripts for VEG/PF mRNAs were detected in the uterus of the rat by reverse transcription polymerase chain reaction. The mRNAs for the VEG/PF164 and VEG/PF120 subunits were the dominant forms expressed. Treatment with both estradiol (E2) and estriol (E3) rapidly induced an increase in the level of the two smaller transcripts. The increase was detectable as early as 0.5-1 h and peaked at 2 h. Levels of the two smaller transcripts then declined, but remained above control levels for 24 h. The degree of stimulation of VEG/PF mRNA levels was 8-fold at 2 h. VEG/PF188 mRNA levels were higher by 6 h compared to control values. The increase in VEG/PF mRNA levels in response to E2 was not contingent upon de novo protein synthesis, as it was not blocked by cycloheximide. The increase occurred as rapidly as that of the mRNA for Zif268, an estrogen-induced transcription factor. Progesterone also stimulated the expression (at 6 h) of VEG/PF164 and VEG/PF120, but not that of VEG/PF188. We conclude that the VEG/PF gene is expressed in the rat uterus, and that mRNA levels are rapidly enhanced by estrogen. This response suggests that VEG/PF may be involved in the estrogen-induced increase in permeability and proliferation of uterine blood vessels. The identification of VEG/PF as a primary response gene also suggests that VEG/PF expression may be a prerequisite for the subsequent expression or action of other growth factors in the uterus. PMID- 8344221 TI - Potential role of 12 hydroxyeicosatetraenoic acid in angiotensin II-induced calcium signal in rat glomerulosa cells. AB - Recent evidence suggests that 12 hydroxyeicosatetraenoic acid (12HETE), a product of the 12 lipoxygenase (LO) pathway of arachidonic acid metabolism, may have a role in mediating angiotensin II (AII)-induced aldosterone secretion. The present study examined the possible role of the 12 LO product 12HETE in AII-induced calcium ([Ca++]i) signals in rat glomerulosa cells. The addition of 12HETE to glomerulosa cells induced a dose-dependent (10(-6)-10(-8) M) rise in [Ca++]i levels that was sustained over 15 min. The effects of 12HETE on [Ca++]i were attenuated but not blocked by nifedipine (5 x 10(-6) M) and were preserved in a calcium-free medium, suggesting mobilization of intracellular calcium stores. Furthermore, the 12HETE-mediated rise in [Ca++]i was almost entirely abolished by dantrolene. In parallel, 12HETE reversed the inhibitory effect of nifedipine on AII-induced aldosterone secretion [AII (10(-9) M) - 36 +/- 7, AII + nifedipine (5 x 10(-6) M) - 13 +/- 2, AII + nifedipine + 12HETE (5 x 10(-8) M) - 27 +/- 4 ng/10(6) cells]. Dantrolene also inhibited AII-dependent aldosterone secretion (AII 10(-9) M - 75.8 +/- 5.6, AII + dantrolene 10(-6) M 45.5 +/- 8.8 ng/10(-6) cells), but this inhibition could not be reversed by 12HETE 10(-8) M (45.4 +/- 10.6 ng/10(6) cells). The LO blockers baicalein and BW755C inhibited the effect of AII on aldosterone production and on [Ca++]i in a parallel fashion. During LO blockade, the addition of 12HETE (10(-7) M) restored the AII-induced rise in [Ca++]i. Collectively, these observations suggest that activation of the LO pathway in the rat adrenal glomerulosa contributes to change in cytosolic calcium, which may be important for the steroidogenic effect of AII. PMID- 8344222 TI - Pleiotropic influence of triiodothyronine on thymus physiology. AB - It is well demonstrated that the thymus gland is under neuroendocrine control. Thymic endocrine function can be modulated by a variety of hormones including those secreted by the thyroid gland. This prompted us to investigate putative influences of T3 in further aspects of thymus physiology. We showed that T3 treated animals exhibited an increase in thymus weight, cellularity and cycling cells. Moreover, Thy1+ thymocytes as well as CD4-CD8 defined subsets were augmented in absolute numbers, whereas PgP.1+ cells increased in both absolute and percentage values. In parallel, the total numbers of thymic nurse cells were also increased. Regarding the expression of extracellular matrix components (ECM) by microenvironmental cells, we observed an enhancement in the intrathymic ECM upon T3 in vivo treatment. Similar effects were found in vitro by treating a thymic epithelial cell line or thymic nurse cell-derived epithelial cultures with T3. This treatment also increased the expression of ECM receptors by thymic epithelial cultures. Interestingly, an enhancement in thymocyte/thymic epithelial cell adhesion ratio was observed after T3 treatment of epithelial cells. Our data suggest that T3 exerts a pleiotropic effect upon thymus physiology, stimulating thymocyte differentiation, not only by modulating epithelial cell hormonal secretion but also their production of ECM proteins and respective receptors. PMID- 8344223 TI - Distribution of estrogen receptor-immunoreactive cells in the sheep brain. AB - The distribution of immunoreactive (IR) estrogen receptor (ER)-containing cells was studied in the brains of adult Suffolk ewes using a rat monoclonal antibody (H222) which recognizes the human estrogen receptor. IR cells were characterized by dense nuclear reaction product, and in some instances, cytoplasmic immunostaining which filled dendrite-like processes. The greatest densities of ER IR cells were found in the medial preoptic area, the mediobasal hypothalamus, and in a number of limbic system structures (amygdala, bed nucleus of the stria terminalis, lateral septum). ER-IR cells were found at lower densities in several other subregions of the hypothalamus and limbic system, and in the periaqueductal gray of the caudal midbrain. Cytoplasmic ER immunoreactivity was most prominent among ER-IR cells in the ventrolateral-ventromedial nucleus, the bed nucleus of the stria terminalis, the midbrain periaqueductal gray, and some ER-IR cells in the substantia innominata. The distribution of ER-containing cells in the sheep brain closely parallels that seen in other mammals. ER-IR cells are found in sites such as the medial preoptic area and ventrolateral-ventromedial hypothalamus which have been implicated as targets in this species and others for the influence of estradiol on sexual behavior and reproductive neuroendocrine function. PMID- 8344224 TI - Fos expression during the estradiol-induced gonadotropin-releasing hormone (GnRH) surge of the ewe: induction in GnRH and other neurons. AB - The protein product of the protooncogene c-fos was used as a marker of cellular activation in an attempt to identify those neurons in the preoptic area and hypothalamus that participate in generation of the estradiol-induced surge of GnRH in the ewe. GnRH- and Fos-expressing cells were identified immunocytochemically, and the percent of coexpression was determined in three states: mid-luteal phase (low GnRH release, n = 6); short-term ovariectomy (high episodic GnRH release, n = 6); and induced GnRH surge (high sustained release, n = 8). To induce the GnRH surge, a follicular phase rise in circulating estradiol was simulated in a physiological model for the estrous cycle. Serum LH was measured as an indicator of GnRH release. In the luteal phase, LH was basal, indicating low GnRH secretion. Few cells expressed Fos; these were not GnRH cells. Despite high intermittent GnRH release in short-term ovariectomized ewes, GnRH cells did not express Fos. During the surge (sustained high GnRH release), 41 +/- 8% of GnRH cells expressed Fos; these cells were dispersed throughout the field of distribution of GnRH neurons. In addition to Fos in GnRH-positive cells, many more non-GnRH cells in the preoptic area, anterior hypothalamus, and ventrolateral hypothalamus expressed Fos during the surge than in the luteal phase or after ovariectomy. We suggest that Fos expression in GnRH cells is markedly increased by the positive feedback action of estradiol (surge), whereas short-term removal of negative feedback (ovariectomy) has little, if any, effect, despite increased GnRH release in both states. Since estradiol induces Fos expression in far more than GnRH neurons, our results also suggest that estradiol activates other cells, some of which may be part of a neuronal chain leading to GnRH surge generation, and some of which may be related to other neural actions of estradiol, such as estrous behavior. PMID- 8344225 TI - Plural cells organize thyroid follicles through aggregation and linkage in collagen gel culture of porcine follicle cells. AB - Some follicle cells organize thyroid follicles through proliferation of single cells in collagen gel culture. The aim of this study was to clarify whether two or more (plural) cells can form follicles through aggregation and linkage in this culture system. To address this question, we performed collagen gel culture of porcine follicle cells, using cell labeling with PKH 2 dye. A mixture of dye labeled and nonlabeled cells was cultured in collagen gel. Organized follicles consisted of both dyed and nondyed cells. This suggested that plural cells reconstructed follicles through aggregation and linkage. To further confirm this finding, cells embedded in collagen gel were cultured in inhibition of cell proliferation with 2 micrograms/ml aphidicolin. Forty to 60 percent of the cells formed follicles, which did not grow larger. Electron microscopy showed that intracytoplasmic cavities appeared in the cells. In contrast, 20-30% of the embedded cells developed into cavity-embracing single cells, which remained signet rings. These results indicate that follicle cells organize follicles in collagen gel culture by two means: through cell division of cavity-embracing single cells and through aggregation and linkage of plural cells. PMID- 8344226 TI - Mass spectrometric analysis of the fragments produced by cleavage and reduction of rat prolactin: evidence that the cleaving enzyme is cathepsin D. AB - The site(s) at which mammary tissue enzymatically cleaves rat (r) PRL, and the possibility that the cleaving activity is cathepsin D, were investigated using mass spectrometry and enzyme inhibitors. Cleavage of intact rPRL [22,566 atomic mass units (amu)] by either mammary gland-conditioned medium or cathepsin D (both at pH 3) reduced the mass of the molecule by 397 amu. Subsequent reduction of the large rPRL fragment cleaved by either method generated two fragments of 16,364 and 5808 amu. The mass of the smaller fragment is consistent with the report of Vick et al. (Biochim Biophys Acta 931: 196-204, 1987) that its amino-terminal residue is Ser149. These results indicate that both enzyme preparations cleave rPRL by excision of the tripeptide Leu-Val-Trp (mass = 397 amu) between residues 145 and 149. The ability of both enzyme preparations to cleave rPRL at pH3 was inhibited by pepstatin A but not by phenylmethane sulfonyl fluoride, and both preparations were essentially inactive at pH7. Accordingly, the PRL-cleaving activity of rat mammary tissue is probably cathepsin D. PMID- 8344228 TI - The effects of ambient NO2 on lung function in primary schoolchildren. AB - The effect of ambient NO2 on lung function was investigated in a sample of 423 schoolchildren. At each of four locations NO2 was monitored continuously. Over a 6-month period from January to June 1990 two surveys were performed and spirometry recorded each time for each child. Linear regression was used to estimate the effect of NO2 for different time intervals preceding lung function testing. A decrease of NO2 between surveys was significantly associated with a higher forced vital capacity (FVC) at the second survey. For each microgram/m3 NO2 decrease the model predicted an increase in FVC of 1.5 ml [for the 2-hr mean (P < 0.05)] and 3.1 ml [for the 12-hr mean (P < 0.01)]. We conclude that even at NO2 levels below current air-quality standards children demonstrate significant changes in lung function. PMID- 8344227 TI - Reproductive hormones modulate angiotensin II AT1 receptors in the dorsomedial arcuate nucleus of the female rat. AB - Angiotensin II AT1 receptors are highly localized in the dorsomedial arcuate nucleus. AT1 receptor number is very low during proestrus and in ovariectomized and male rats, and is high only during the estrus phase of the estrous cycle and after ovariectomized rats receive a sequential estrogen-progesterone treatment. Our results suggest that the mechanism of the estrogen-progesterone inhibition of the prolactin surge may involve the selective stimulation of dorsomedial arcuate AT1 receptors. PMID- 8344229 TI - Immediate-type allergy related to okra (Hibiscus esculentus Linn) picking and packing. AB - Two workers (cases A and B) engaged in picking and packing okra who had complaints of work-related allergic symptoms showed distinct positive intradermal reactions to two brands of okra extracts only with thresholds of 1 x 10(-8) w/v for Case A and 1 x 10(-6) w/v for Case B. Both also showed positive reactions to okra extracts in the Prausnitz-Kustner test and in the provocative nasal test. The radioallergosorbent test scores to the okra extract were determined to be 2 (defined as clear positive) for Case A and 1 (border line) for Case B. These findings indicated that the allergic conditions of these cases were from an IgE mediated immediate-type allergy induced by handling okra. To confirm the etiology of the two cases 14 farmers engaged in picking and packing okra were examined. Among them, 8 subjects (57%) showed positive intradermal reactions to okra extracts. A close association between intradermal reactions to okra extracts and complaints of work-related allergic symptoms was seen in these subjects. These results confirm that the okra may be capable of inducing IgE-mediated immediate type allergy to workers handling okra. PMID- 8344230 TI - Assessment of the health impact of environmental exposure to cadmium: contribution of the epidemiologic studies carried out in Belgium. PMID- 8344231 TI - Arsenic and cadmium exposure in children living near a smelter complex in San Luis Potosi, Mexico. AB - The main purpose of this study was to assess environmental contamination by arsenic and cadmium in a smelter community (San Luis Potosi City, Mexico) and its possible contribution to an increased body burden of these elements in children. Arsenic and cadmium were found in the environment (air, soil, and household dust, and tap water) as well as in the urine and hair from children. The study was undertaken in three zones: Morales, an urban area close to the smelter complex; Graciano, an urban area 7 km away from the complex; and Mexquitic, a small rural town 25 km away. The environmental study showed that Morales is the most contaminated of the zones studied. The range of arsenic levels in soil (117-1396 ppm), dust (515-2625 ppm), and air (0.13-1.45 micrograms/m3) in the exposed area (Morales) was higher than those in the control areas. Cadmium concentrations were also higher in Morales. Estimates of the arsenic ingestion rate in Morales (1.0 19.8 micrograms/kg/day) were equal to or higher than the reference dose of 1 microgram/kg/day calculated by the Environmental Protection Agency. The range of arsenic levels in urine (69-594 micrograms/g creatinine) and hair (1.4-57.3 micrograms/g) and that of cadmium in hair (0.25-3.5 micrograms/g) indicated that environmental exposure has resulted in an increased body burden of these elements in children, suggesting that children living in Morales are at high risk of suffering adverse health effects if exposure continues. PMID- 8344232 TI - Assessment of sympathetic nerve activity controlling blood pressure in the elderly using head-up tilt. AB - In order to assess age-related changes in sympathetic nerve activity controlling blood pressure, we recorded muscle sympathetic nerve activity, blood pressure, and heart rate during head-up tilt in 10 healthy elderly (69-75 years) and 16 healthy young (19-23 years) subjects. The elderly had significantly lower responsiveness of muscle sympathetic nerve activity to postural change than did the young subjects. In the elderly, marked rise in blood pressure without increase in muscle sympathetic nerve activity was observed in nearly upright position during head-up tilt, whereas this phenomenon was not observed in the young. We conclude that neural control function of blood pressure during head-up tilt in the elderly differs from that in the young, which may be due to age related change in baroreflex function. PMID- 8344233 TI - A prospective cohort study of the chronic effects of solvent exposure. AB - The issue of the health effects of long-term exposure to solvents still attracts considerable debate, particularly among regulators and policymakers. This is especially true for studies of neurobehavioral effects. A major reason for this debate is that cross-sectional research designs are almost universally used in this area. Cross-sectional studies suffer from problems of possible confounding by a range of unknown factors and also usually from poor estimates of exposure. This study is an attempt to solve this problem by using an inception cohort design in which the subjects are measured at the beginning of their exposure and then at intervals while their exposure continues. Two hundred first-year apprentice vehicle spray painters were entered into the study within 6 months of beginning their apprenticeship together with a comparison group of 76 first-year apprentice electricians and 49 first-year apprentice metal fabricators. Measures of neurobehavioral function using a test battery based on an information processing model were made at study entry and will be made annually. In addition apprentice's assessments of their own exposure are being made annually and compared with workplace-exposure assessments. So far measures have been made at the beginning of the second year for the entire cohort and at the beginning of the third year for one-third of the cohort. This paper is a description of the results for this one-third. The results suggest that there were no significant changes in neurobehavioral function in the first 2 years of exposure to solvents. However, the results of workplace monitoring suggest that exposure is considerably below current exposure standards for solvents during this time. PMID- 8344234 TI - Assessment of central, peripheral, and autonomic nervous system functions in vibrating tool operators: neuroelectrophysiological studies. AB - To evaluate the effects of vibrating tool operation (i.e., combined stressors of local vibration, noise, cold climate, and heavy work) on the central, peripheral, and autonomic nervous systems, the short-latency somatosensory and brain stem auditory evoked potentials (SSEP and BAEP), the distribution of sensory median nerve conduction velocities (DCV), conventional median nerve conduction velocities (NCV), and the electrocardiographic R-R interval variability (CVRR) were measured in three groups of male vibrating tool operators and age-matched male healthy adults. Two components of the CVRR reflecting parasympathetic activity (C-CVRSA) and sympathetic activity (C-CVMWSA) were also examined. In the first group of vibrating tool operators (15 chain saw operators), all parameters of DCV (V10-V90 velocities) and sensory and motor nerve conduction velocities of NCV were significantly slowed. All peak latencies of SSEP were significantly prolonged, while no significant differences were found in the interpeak latencies of SSEP. The N9 peak latency of SSEP was significantly related to total working days. In the second group of the operators (12 chain saw and 8 brush saw operators), the I-V interpeak and V peak latencies of BAEP were significantly prolonged in the 12 chain saw operators; the I-V interpeak latency of BAEP was significantly correlated with the working years in the 8 brush saw operators. In the third group of vibrating tool operators, i.e., 13 operators with a history of vibration-induced white finger (VWF group) and 11 operators without VWF (non-VWF group), both the CVRR and C-CVRSA were significantly reduced in the VWF group; only the CVRR was significantly reduced in the non-VWF group. Similarly, the faster velocities of DCV (V70, V80, and V90 velocities) were significantly slowed in both the VWF and non-VWF groups. In conclusion, it is suggested that vibrating tool operation affects the faster sensory and motor nerve fibers, the parasympathetic activity, and the auditory pathway from the acoustic nerve to the brain stem. PMID- 8344235 TI - Nd and P300 in healthy volunteers. AB - We attempted to standardize values of the attention-related negative potential (Nd) and the P300 in 100 healthy volunteers (50 females, 50 males) who were given the task of making dichotic syllable discriminations requiring key-press responses. Ages ranged between 18 and 59 years. Nd was found to be maximum in the Fz region, P300 being maximum in the Pz region. The means and standard deviations of the Nd and P300 areas in their maximum regions were 554.1 +/- 307.8 microV.msec and 2148.5 +/- 1261.5 microV.msec, respectively. After being transformed into logarithmic values, the distribution patterns of the Nd and P300 areas followed a Gaussian distribution. When the lower limit of normal values was tentatively assigned to mean--2 SD using logarithmically transformed data for both Nd and P300, 94% of the subjects were found to display values above the lower normal limit for Nd, and 95% for P300. Neither Nd nor P300 areas correlated with age, while P300 latencies displayed a weak positive correlation with age. Females displayed relatively larger values than males for Nd and P300 areas and P300-peak amplitudes. Females and males showed nearly equal P300-peak latencies. PMID- 8344236 TI - Subjective symptoms and neurobehavioral performances of ex-mercury miners at an average of 18 years after the cessation of chronic exposure to mercury vapor. Mercury Workers Study Group. AB - In order to determine if there are any residual effects of long-term exposure to mercury vapor, neurobehavioral tests were given to ex-mercury miners about 18 years after the cessation of mercury exposure. Seventy-six male ex-mercury miners who had been exposed to relatively high concentrations of mercury vapor (over 1.0 mg/m3) and with a past history of mercury intoxication were compared to age (+/- 3 years)-, sex-, and years of education-matched controls. Although the extent of the workers' symptoms caused by mercury poisoning, termed erethismus merculialis, markedly decreased after the cessation of exposure, the prevalence of neurological symptoms (such as hand tremors, headaches, and slurred speech) and symptoms of senility (such as low-back pain, loss of sexual desire) in the ex miners was significantly higher than those in the controls. Matched-pair analysis showed that performances of motor coordination, Simple reaction time, and Short term memory in the ex-miners were significantly deteriorated compared to those of controls. There are slight but persistent effects on neurobehavioral function, especially on motor coordination function, among mercury miners more than 10 years after the cessation of exposure. PMID- 8344237 TI - Neurobehavioral effects of chronic occupational exposure to organic solvents among Japanese industrial painters. AB - To investigate the relationship between chronic exposure to organic solvents and changes in central nervous system function, industrial painters were compared with an age- and education-matched referent group of nonexposed workers. Eighty one male painters completed a symptom questionnaire. Twenty painters underwent both questionnaire and neuropsychological examinations. From the results of pairwise comparisons of the symptoms, dry and scaly skin, being easily depressed without reason, coldness of hands and legs, being easily irritated without reason, loss of appetite, dizziness, and unsteadiness occurred statistically significantly more often among the exposed subjects than among the referents. Performances on the Digit symbol test and vocabulary test scores (synonyms) in exposed subjects were significantly lower than those of controls. In multiple regression models, controlling for age, education, and alcohol intake, a significant relation was found between the duration of the solvent exposure and poor performance in both the Block design and Digit span tests. The relation between toluene exposure and poor performance in both the Santa Ana coordination test and the Benton visual retention test was also significant. The results suggest that a symptom inquiry and some behavioral tests are helpful for detecting the possible effects of exposure to low levels of organic solvents. However, no consistent pattern was observed in regard to the effects of organic solvent exposure on neurobehavioral function, which is coincident with the type I toxic central nervous system disorder as classified by the World Health Organization. PMID- 8344238 TI - Relations of work stress to alcohol use and drinking problems in male and female employees of a computer factory in Japan. AB - To examine the effects of work stressors on alcohol use and drinking problems as well as a model of stress-induced drinking in Japanese male and female workers, a total of 2581 employees of a computer factory were surveyed using mailed questionnaires. Five psychosocial work stressors, overtime, rotating shift, frequency of drinking, amount of alcohol consumed per drinking occasion, and drinking problems, and depressive symptoms were assessed. The hierarchical linear and logistic regression analyses were conducted in 1043 male and 255 female current drinkers aged 20 years or older. The results suggested that overtime and lack of intrinsic work rewards are main factors for heavy and problem drinking in Japanese male workers and that ambiguity about job future is a factor for heavy drinking in Japanese female workers. However, the model of stress-induced drinking was supported neither in males nor in females, suggesting that the effects of these work stressors on heavy and problem drinking are not mediated by depressive symptoms. PMID- 8344239 TI - Assessment of the effects of occupational and environmental factors on all faster and slower large myelinated nerve fibers: a study of the distribution of nerve conduction velocities. AB - To assess the effects of occupational and environmental factors on all faster and slower large myelinated peripheral nerve fibers, we measured the distribution of nerve conduction velocities (DCV) in men exposed to local vibration, lead, thallium, styrene, mixed solvents, and alcohol as well as in diabetic patients. The results indicated that conduction velocities of faster large myelinated nerve fibers are more sensitive to most toxic chemicals and physical factors than those of the slower fibers. Further studies are needed to investigate which of the DCV and the conventional peripheral nerve conduction velocity is a more sensitive indicator of the subclinical effects of these factors and whether zinc and copper antagonize the effects of lead on the DCV. PMID- 8344240 TI - Are faster or slower large myelinated nerve fibers more sensitive to chronic lead exposure? A study of the distribution of conduction velocities. AB - To determine which of the faster and slower large myelinated nerve fibers (alpha fiber group) are more sensitive to chronic lead exposure, the distribution of nerve conduction velocities (DCV) as well as conventional sensory nerve conduction velocity (SCV) were measured once a month for 20 and 11 months in two male lead workers with blood lead concentrations of 70 to 121 and of 63 to 85 micrograms/dl, respectively. Differences in the frequency beyond the "normal" ranges between conduction velocities of faster nerve fibers (V80, V90, or SCV) and those of slower fibers (V10 or V20) were analyzed by the McNemar test. In the two lead workers, the values below the lower normal limits for the V80 and V90 velocities were more frequent than those for the V10 and V20 velocities; similarly, lower values for the SCV were more frequent than those for the V10 and V20 velocities (P < 0.05). It was suggested that faster nerve fibers are more sensitive to chronic lead exposure than slower nerve fibers. These findings agree with our published data on the effects of local vibration, thallium, n-hexane, styrene, mixed organic solvents, alcohol dependency, and diabetes mellitus. PMID- 8344241 TI - Mitotic stability and nuclear inheritance of integrated viral cDNA in engineered hypovirulent strains of the chestnut blight fungus. AB - Transmissible hypovirulence is a novel form of biological control in which virulence of a fungal pathogen is attenuated by an endogenous RNA virus. The feasibility of engineering hypovirulence was recently demonstrated by transformation of the chestnut blight fungus, Cryphonectria parasitica, with a full-length cDNA copy of a hypovirulence-associated viral RNA. Engineered hypovirulent transformants were found to contain both a chromsomally integrated cDNA copy of the viral genome and a resurrected cytoplasmically replicating double-stranded RNA form. We now report stable maintenance of integrated viral cDNA through repeated rounds of asexual sporulation and passages on host plant tissue. We also demonstrate stable nuclear inheritance of the integrated viral cDNA and resurrection of the cytoplasmic viral double-stranded RNA form in progeny resulting from the mating of an engineered hypovirulent C. parasitica strain and a vegetatively incompatible virulent strain. Mitotic stability of the viral cDNA ensures highly efficient transmission of the hypovirulence phenotype through conidia. Meiotic transmission, a mode not observed for natural hypovirulent strains, introduces virus into ascospore progeny representing a spectrum of vegetative compatibility groups, thereby circumventing barriers to anastomosis-mediated transmission imposed by the fungal vegetative incompatibility system. These transmission properties significantly enhance the potential of engineered hypovirulent C. parasitica strains as effective biocontrol agents. PMID- 8344242 TI - The methyl-accepting transducer protein HtrI is functionally associated with the photoreceptor sensory rhodopsin I in the archaeon Halobacterium salinarium. AB - We have investigated the functional relationship between two proteins involved in the photosensory system of the archaeon Halobacterium salinarium: the photoreceptor sensory rhodopsin I (SRI) and the halobacterial transducer rhodopsin I (HtrI), which has been proposed to be the putative signal transducer of SRI, by genomic DNA analysis of two independent SRI negative mutants, Pho81 and D1. Southern and PCR analyses revealed that both strains bear alterations in the 5' flanking region of the gene encoding SRI, sopI. DNA sequence analysis confirmed the occurrence in this region of htrI, the gene encoding the putative transducer protein. PCR and Northern analyses have shown further that sopI and htrI are expressed as a single transcriptional unit, thus explaining the lack of SRI in mutants with a defective htrI. Expression of the cloned sopI under the control of a heterologous promoter did not restore the SRI-dependent photoresponse in the strain Pho81. Moreover, the photocycling rate of the expressed pigment was clearly lower than in wild type. HtrI is therefore essential for SRI function and most likely modulates the photochemical properties of the photoreceptor via direct physical interaction. Finally, reintroduction of both sopI and htrI into Pho81 and D1 restored the SRI photochemistry and its physiological function. Our results provide the first experimental evidence for the functional coupling between SRI and HtrI and corroborate the proposed model in which HtrI acts as the signal transducer of this archaeal seven-helix photoreceptor in a way analogous to the bacterial chemotaxis transducers. PMID- 8344243 TI - Agonist-induced localized Ca2+ spikes directly triggering exocytotic secretion in exocrine pancreas. AB - We investigated how agonist-induced patterned rises in cytosolic Ca2+ concentration ([Ca2+]i) regulate exocytotic secretion in the rat pancreatic acinar cell. The distribution of [Ca2+]i was visualized with a confocal microscope, which revealed that a Ca2+ ionophore, A23187, induced slow and homogeneous [Ca2+]i rises, while acetylcholine (ACh) always triggered primary Ca2+ spikes at the granular area which bears secretory granules. Secretion was monitored by measuring capacitance with the patch clamp method. Errors in the estimates of membrane capacitance (C) due to changes in conductance (G) were experimentally as well as theoretically evaluated to be one-tenth of the actual signals. We found that A23187 raised G without changing C at a low concentration, while it triggered asynchronous rises in G and C with lags in C, at a high concentration. By contrast, ACh triggered simultaneous rapid rises in G and C. Our results support the hypothesis that exocytotic secretion is less sensitive to Ca2+ than to ion channels and is directly caused by agonist-induced primary Ca2+ spikes at the granular area. It is therefore suggested that spatio-temporal patterns of Ca2+ oscillations could play a key role in exocytotic secretion from the exocrine acinar cell. PMID- 8344244 TI - Genetic and biochemical characterization of ISP6, a small mitochondrial outer membrane protein associated with the protein translocation complex. AB - To search genetically for additional components of the protein translocation apparatus of mitochondria, we have used low fidelity PCR mutagenesis to generate temperature-sensitive mutants in the outer membrane translocation pore component ISP42. A high copy number suppressor of temperature-sensitive isp42 has been isolated and sequenced. This novel gene, denoted ISP6, encodes a 61 amino acid integral membrane protein of the mitochondrial outer membrane, which is oriented with its amino-terminus facing the cytosol. Disruption of the ISP6 gene is without apparent effect in wild type yeast cells, but is lethal in temperature sensitive isp42 mutants. Immunoprecipitation of the gene product, ISP42p, from mitochondria solubilized under mild conditions reveals a multi-protein complex containing ISP6p and ISP42p. PMID- 8344245 TI - Protein import into yeast mitochondria: the inner membrane import site protein ISP45 is the MPI1 gene product. AB - Protein import across both mitochondrial membranes is mediated by the cooperation of two distinct protein transport systems, one in the outer and the other in the inner membrane. Previously we described a 45 kDa yeast mitochondrial inner membrane protein (ISP45) that can be cross-linked to a partially translocated precursor protein (Scherer et al., 1992). We have now purified ISP45 to homogeneity and identified it as the product of the nuclear MPI1 gene. Identity of ISP45 with the MPI1 gene product was shown by microsequencing of three tryptic ISP45 peptides and by demonstrating that an antibody against an Mpi1p-beta galactosidase fusion protein specifically recognizes ISP45. Antibodies monospecific for ISP45 inhibited protein import into right-side-out mitochondrial inner membrane vesicles, but not into intact mitochondria. On solubilizing mitochondria, ISP45 was rapidly converted to a 40 kDa proteolytic fragment unless mitochondria were first denatured with trichloroacetic acid. The combined genetic and biochemical evidence identifies ISP45/Mpi1p as a component of the protein import system of the yeast mitochondrial inner membrane. PMID- 8344246 TI - Lack of assembly of mitochondrial DNA-encoded subunits of respiratory NADH dehydrogenase and loss of enzyme activity in a human cell mutant lacking the mitochondrial ND4 gene product. AB - In most eukaryotic cells, the respiratory chain NADH dehydrogenase (Complex I) is a multimeric enzyme under dual (nuclear and mitochondrial) genetic control. Several genes encoding subunits of this enzyme have been identified in the mitochondrial genome from various organisms, but the functions of these subunits are in most part unknown. We describe here a human cell line in which the enzyme lacks the mtDNA-encoded subunit ND4 due to a frameshift mutation in the gene. In this cell line, the other mtDNA-encoded subunits fail to assemble, while at least some of the nuclear-encoded subunits involved in the redox reactions appear to be assembled normally. In fact, while there is a complete loss of NADH:Q1 oxidoreductase activity, the NADH:Fe(CN)6 oxidoreductase activity is normal. These observations provide the first clear evidence that the ND4 gene product is essential for Complex I activity and give some insights into the function and the structural relationship of this polypeptide to the rest of the enzyme. They are also significant for understanding the pathogenetic mechanism of the ND4 gene mutation associated with Leber's hereditary optic neuropathy. PMID- 8344247 TI - Vps1p, a member of the dynamin GTPase family, is necessary for Golgi membrane protein retention in Saccharomyces cerevisiae. AB - The KEX2-encoded endoprotease of Saccharomyces cerevisiae resides in the Golgi complex where it participates in the maturation of alpha-factor mating pheromone precursor. Clathrin heavy chain gene disruptions cause mislocalization of Kex2p to the cell surface and reduce maturation of the alpha-factor precursor. Based on these findings, a genetic screen has been devised to isolate mutations that affect retention of Kex2p in the Golgi complex. Two alleles of a single genetic locus, lam1 (lowered alpha-factor maturation), have been isolated, which result in inefficient maturation of alpha-factor precursor. In lam1 cells, Kex2p is not mislocalized to the cell surface but is abnormally unstable. Normal stability is restored by the pep4 mutation which reduces the activity of vacuolar proteases. In contrast, the pheromone maturation defect is not corrected by pep4. Organelle fractionation by sucrose density gradient centrifugation shows that Kex2p is not retained in the Golgi complex of lam1 cells. Vacuolar protein precursors are secreted by lam1 mutants, revealing another sorting defect in the Golgi complex. Genetic complementation reveals that lam1 is allelic to the VPS1 gene, which encodes a dynamin-related GTPase. These results indicate that Vps1p is necessary for membrane protein retention in a late Golgi compartment. PMID- 8344248 TI - The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion. AB - Ras GTPase activating protein (GAP) possesses a C-terminal domain that interacts with GTP-bound Ras, and an N-terminal region containing two SH2 domains and an SH3 domain. In addition to its association with Ras, GAP binds stably to autophosphorylated beta PDGF receptors, and to two cytoplasmic phosphoproteins: p62, an RNA binding protein, and p190, which possesses GAP activity towards small guanine nucleotide binding proteins in the Rho/Rac family. To define the region of GAP that mediates these interactions with cellular phosphoproteins, and to investigate the biological significance of these complexes, a truncated GAP polypeptide (GAP-N) containing residues 1-445 was stably expressed in Rat-2 fibroblasts. GAP-N contains the SH2 and SH3 domains, but lacks the Ras GTPase activating domain. Stimulation of cells expressing GAP-N with PDGF induced association of GAP-N with the beta PDGF receptor, and phosphorylation of GAP-N on tyrosine, consistent with the notion that GAP SH2 domains direct binding to the autophosphorylated beta PDGF receptor in vivo. GAP-N bound constitutively to p190 in both serum-deprived and growth factor-stimulated cells. This GAP-N-p190 complex had Rho GAP activity in vitro. The expression of GAP-N in Rat-2 cells correlated with changes in the cytoskeleton and in cell adhesion, typified by the disruption of action stress fibres, a reduction in focal contacts, and an impaired ability to adhere to fibronectin. These results suggest that the N terminal domain of GAP can direct interactions with cellular phosphoproteins in vivo, and thereby exert an effector function which modulates the cytoskeleton and cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344249 TI - trkC encodes multiple neurotrophin-3 receptors with distinct biological properties and substrate specificities. AB - The trkC gene product gp145trkC is a high affinity signaling receptor for neurotrophin-3 (NT-3), a member of the NGF family of neurotrophic factors. We now report that trkC encodes at least two additional tyrosine protein kinase receptors. These receptors, designated TrkC K2 and TrkC K3, have the same amino acid sequences as gp145trkC (now designated TrkC K1) except for the presence of 14 and 25 additional amino acid residues between kinase subdomains VII and VIII, just downstream from the TDYYR motif which encompasses the putative autophosphorylation site of the Trk receptor family. Upon interaction with their cognate ligand, NT-3, all three TrkC receptor isoforms become rapidly phosphorylated on tyrosine residues and induce DNA synthesis in quiescent cells. However, only TrkC K1 has mitogenic activity in NIH3T3 cells and induces neuronal differentiation of PC12 cells. The different biological properties of these TrkC receptor isoforms probably result from their engagement with different signaling pathways. Whereas TrkC K1 phosphorylates phospholipase C gamma 1 and phosphatidylinositol-3 kinase, TrkC K2 and TrkC K3 do not. TrkC K2 and transcripts encoding TrkC K3 have been identified in various structures of the adult murine brain. These observations suggest that the trophic activities of NT 3 in the mammalian nervous system might be mediated by different TrkC receptor isoforms. PMID- 8344250 TI - Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. AB - Tumor necrosis factor (TNF) has cytotoxic and gene-inductive activities on several cell types. Previous studies on L929 fibrosarcoma cells have revealed that the mitochondrial electron transport system plays a key role in inducing TNF cytotoxicity, presumably by the formation of reactive oxygen intermediates (ROI). Here we report that mitochondria-derived intermediates are not only cytotoxic but, in addition, function as signal transducers of TNF-induced gene expression. The activation of NF kappa B, which fulfills an important role in TNF-induced gene transcription, could be blocked by interference with the mitochondrial electron transport system. Furthermore, antimycin A, a mitochondrial inhibitor that increases the generation of ROI, potentiated TNF-triggered NF kappa B activation. The dual role of mitochondria-derived intermediates in cytotoxicity and immediate-early gene induction of TNF was further substantiated by isolating L929 subclones which lacked a functional respiratory chain. This depletion of the mitochondrial oxidative metabolism resulted in resistance towards TNF cytotoxicity, as well as in inhibition of NF kappa B activation and interleukin-6 gene induction by TNF. These findings suggest that mitochondria are the source of second messenger molecules and serve as common mediators of the TNF-cytotoxic and gene-regulatory signaling pathways. PMID- 8344252 TI - CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15. AB - The mitotic inducer p34cdc2 requires association with a cyclin and phosphorylation on Thr161 for its activity as a protein kinase. CAK, the p34cdc2 activating kinase, was previously identified as an enzyme necessary for this activating phosphorylation. We confirm here that CAK is a protein kinase and describe its purification over 13,000-fold from Xenopus egg extracts. We further show that CAK contains a protein identical or closely related to the previously identified Xenopus MO15 gene: p40MO15 copurifies with CAK, and an antiserum to p40MO15 specifically depletes cAK activity. CAK appears to be the only protein in Xenopus egg extracts that can activate complexes of either p34cdc2 or the closely related protein kinase, p33cdk2, with either cyclin A or cyclin B. The sequence similarity between p40MO15 and p34cdc2, and the approximately 200 kDa size of CAK, suggest that p40MO15 may itself be regulated by subunit association and by protein phosphorylations. PMID- 8344251 TI - The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues. AB - Phosphorylation of Thr161, a residue conserved in all members of the cdc2 family, has been reported to be absolutely required for the catalytic activity of cdc2, the major regulator of eukaryotic cell cycle. In the present work, we have purified from starfish oocytes a kinase that specifically activates cdc2 in a cyclin-dependent manner through phosphorylation of its Thr161 residue. Our most highly purified preparation contained only two major proteins of apparent M(r) 37 and 40 kDa (p37 and p40), which could not be separated from each other without loss of activity. The purified kinase was found to phosphorylate not only cdc2, but also cdk2 and a divergent cdc2-like protein from Caenorhabditis, in chimeric complexes including both mitotic and G1/S cyclins. Extensive microsequencing of p40 did not reveal any convincing homology with any known protein. In contrast, p37 is the starfish homologue of the M015 gene product, a kinase previously cloned by homology probing from a Xenopus cDNA library. As expected, immunodepletion of the MO15 protein depleted Xenopus egg extracts of CAK (cdk activating kinase) activity, which was recovered in immunoprecipitates. Taken together, the above results demonstrate that MO15 is a gene conserved throughout evolution (at least from echinoderms to vertebrates) that encodes the catalytic subunit of a protein kinase that activates cdc2-cdks complexes through phosphorylation of Thr161 (or its homologues). PMID- 8344253 TI - Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation. AB - Immunization of mice with gp96/grp94 heat shock proteins (HSPs) elicits tumor specific cellular immunity to the tumors from which gp96 is isolated. However, the cDNA sequence of gp96 is identical among tumors and normal tissues. This raises the question regarding the structural basis of the specific immunogenicity of gp96. As HSPs bind a wide array of molecules including peptides, we have proposed that gp96 may not be immunogenic per se, but may chaperone antigenic peptides. Furthermore, gp96 is localized predominantly in the lumen of the endoplasmic reticulum (ER) suggesting that it may act as a peptide acceptor and as accessory to peptide loading of MHC class I molecules. We demonstrate here that gp96 molecules contain ATP-binding cassettes, bind ATP and possess an Mg(2+) dependent ATPase activity. Gp96 preparations are also observed to contain tightly bound peptides, which can be eluted by acid extraction. These properties of gp96 are consistent with its proposed roles in chaperoning antigenic peptides and in facilitating MHC class I--peptide assembly in the ER lumen. We present a model to explain how interaction of gp96 with MHC class I may result in transfer of peptides to the latter. PMID- 8344254 TI - Novel proteins associated with MHC class I antigens in cells expressing the adenovirus protein E3/19K. AB - Assembly of histocompatibility class I antigens (MHC) with beta 2-microglobulin (beta 2m) and peptide takes place in the rough endoplasmic reticulum (ER). At present, it is unclear why peptides generated in the cytosol or ER by proteolysis are not further degraded. Also, it is an open question whether assembly and/or peptide binding is self-instructive or is promoted by additional molecules, for example, chaperones. We previously demonstrated that the adenovirus glycoprotein E3/19K binds to human and some mouse MHC molecules in the ER, interfering with their transport to the cell surface. Here we show that immunoprecipitates from human cells that express transfected E3/19K and murine MHC Kd molecules not only contain MHC heavy chain, beta 2m and E3/19K but also two additional proteins with apparent molecular weights of 100 kDa and 110 kDa. Biochemical characterization of these proteins, designated p100 and p110, demonstrates that they are transmembrane glycoproteins with a similar if not identical protein backbone. Consistent with a role as chaperones, we find that glucose starvation induces complex formation between p100/110 and MHC-E3/19K. Most interestingly, p100 and p110 are displaced from the complex by addition of Kd-specific peptides. Therefore, p100 and p110 might be chaperones that promote correct folding of MHC antigens and/or peptide binding to MHC. PMID- 8344255 TI - MHC class I gene expression is negatively regulated by the proto-oncogene, c-jun. AB - The trans-acting factor AP-1 is a heterodimeric complex composed of c-Jun and c Fos family proteins which bind and regulate genes containing a TPA responsive enhancer element. Although AP-1 binding sites have been identified within the regulatory region of major histocompatibility complex (MHC) class I genes in vitro, the role of AP-1 in regulating MHC class I transcription in vivo has not been investigated previously. The present study demonstrates that expression of c Jun results in decreased MHC class I promoter activity as determined in cotransfection assays of an MHC class I reporter construct with a c-Jun expression construct. The c-Jun responsive element is located between bp -440 and -431 upstream of initiation of transcription as determined both functionally and by direct binding of purified c-Jun. Furthermore, over-expression of c-Jun reduced the steady state levels of endogenous MHC class I RNA in murine L cells by approximately 10-fold. These data indicate that c-Jun/AP-1 acts as a negative trans-acting factor that down-regulates MHC class I gene expression. PMID- 8344256 TI - Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal mediated repression in Drosophila. AB - The dorsal (dl) protein gradient determines patterns of gene expression along the dorsal-ventral axis of the Drosophila embryo. dl protein is at peak levels in ventral nuclei of the embryo where it activates some genes (twist and snail) and represses others [zerknullt (zen), decapentaplegic and tolloid]. It is a member of the rel family of transcription factors and interacts with specific DNA sequences in the regulatory regions of its target genes. These sequences (dl binding sites), when taken from the context of either an activated or repressed promoter, mediate transcriptional activation of a heterologous promoter, but not repression. We found that T-rich sequences close to the dl binding sites in the silencer region of the zen promoter are conserved between three Drosophila species. Using this sequence information we defined a minimal element that can mediate repression of a heterologous promoter. This element interacts with at least two factors present in embryonic extracts, one of which is dl protein. The other factor binds to the T-rich site. Point mutations in either site abolish ventral repression in vivo. In addition, mutations in the T-rich site cause ectopic expression in ventral regions indicating that the minimal silencer was converted into an enhancer. PMID- 8344257 TI - Conversion of a dorsal-dependent silencer into an enhancer: evidence for dorsal corepressors. AB - In Drosophila, the dorsal (dl) morphogen gradient initiates the differentiation of the embryonic mesoderm and neuroectoderm by activating the expression of regulatory genes (e.g. twist and snail) in a concentration-dependent manner. dl also functions as a repressor that establishes the dorsal epidermis and amnioserosa by restricting regulatory genes such as dpp and zen to dorsal regions of the embryo. The ability of dl to function as both an activator and repressor distinguishes it from the bicoid morphogen, which appears to function solely as an activator. In an effort to determine how dl functions as a repressor we have performed a detailed characterization of a zen silencer element, called the VRE, which mediates ventral repression in response to the dl gradient. A minimal 110 bp VRE sequence is identified, which is able to silence the ventral expression of a heterologous promoter. This sequence contains two dl binding sites as well as binding sites for additional nuclear factors present in early embryos. Mutations in the latter binding sites convert the minimal VRE into an enhancer, which mediates transcriptional activation in ventral regions in response to dl. These results suggest that dl is intrinsically an activator, but is converted into a potent silencer when it interacts with neighboring corepressors. PMID- 8344259 TI - Common features in DNA recognition helices of eukaryotic transcription factors. AB - Eukaryotic transcription factors which use an alpha-helix for DNA recognition, including the leucine zipper and homoeo domain proteins, have common features in the amino acid sequence of the DNA recognition helix, and also in the way this helix interacts with DNA. These factors all share a similar 12 residue segment in the DNA recognition helix, which is named the probe helix, since it covers all the pertinent interactions. Moreover, in all cases the interactions can be divided into two parts: the Arg/Lys residues at positions 7, 9, 11 and 12 in the C-terminal half of the segment contact phosphate groups, whereas the N-terminal half interacts with the DNA bases by using residues at positions 1, 4, 5 and 8. The residue occupying position 1 is the most important for sequence specific DNA recognition. Similar 12 residue sequences are found in the DNA binding domain of many transcription factors including those of the TEA family, the Myc type of bHLH family, the MADS family, the Ets family and the OmpR family. These generalities show that it might be possible to find a stereochemical code which explains three-dimensional interactions between DNA and an alpha-helix of this type. PMID- 8344258 TI - The Brachyury gene encodes a novel DNA binding protein. AB - Brachyury (T) mutant embryos are deficient in mesoderm formation and do not complete axial development. The notochord is most strongly affected. The T gene is expressed transiently in primitive streak-derived nascent and migrating mesoderm cells and continuously in the notochord. Ectopic expression of T protein in the animal cap of Xenopus embryos results in ectopic mesoderm formation. The T protein is located in the nucleus. These and other data suggested that the T gene might be involved in the control of transcriptional regulation. In an attempt to demonstrate specific DNA binding of the T protein we have identified a consensus sequence among DNA fragments selected from a mixture of random oligomers. Under our experimental conditions T protein binds as a monomer to DNA. This property resides in the N-terminal domain of 229 amino acid residues which is strongly conserved between the mouse protein, and its Xenopus and zebrafish homologues. The latter proteins also recognize the consensus DNA binding site. We suggest that the T protein is involved in the control of genes required for mesoderm formation, and for the differentiation and function of chorda mesoderm. PMID- 8344260 TI - Genetic analysis of the leucine heptad repeats of Lac repressor: evidence for a 4 helical bundle. AB - Gel-filtration experiments indicate that a peptide (P2) composed of the basic region of GCN4 fused to the leucine heptad repeats of Lac repressor forms tetrameric aggregates. Gel-shift experiments were performed to determine the orientation of the helices in the tetrameric P2 aggregate. Sandwich-complex formation of peptide P2 with two DNA fragments containing two symmetrical CRE binding sites (5'-ATGACGTCAT-3') at a distance of 21 bp suggests antiparallel aggregation of the Lac leucine heptad repeats. Thus, we conclude that the leucine heptad repeats of Lac repressor have the ability to form homomeric 4-helical bundles with an antiparallel arrangement of the helices. This topology enables the two DNA fragments in the sandwich complexes to be held together by two tetramers of peptide P2. Replacement of the uncharged amino acids of the helical g and e positions of peptide P2 by the corresponding charged residues of GCN4 (peptide P4) results in a dimeric and parallel aggregation of the leucine heptad repeats, and consequently abolishes the potential to form sandwich structures. Similarly, a hybrid Lac repressor in which the GCN4 leucine zipper replaces the natural Lac leucine heptad repeats forms dimers only. It regains the ability to form tetramers when the charged amino acids in helical positions g and e are replaced by uncharged alanines. PMID- 8344261 TI - SAR-dependent mobilization of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1-depleted chromatin. AB - An experimental assay was developed to search for proteins capable of antagonizing histone H1-mediated general repression of transcription. T7 RNA polymerase templates containing an upstream scaffold-associated region (SAR) were highly selectively repressed by H1 relative to non-SAR control templates. This is due to the nucleation of H1 assembly into flanking DNA brought about by the numerous A-tracts (AT-rich sequences containing short homopolymeric runs of dA.dT base pairs) of the SAR. Partial, selective titration of these A-tracts by the high mobility group (HMG) protein HMG-I/Y led to the complete derepression of transcription from the SAR template by inducing the redistribution of H1 on to non-SAR templates. SARs are associated with many highly transcribed regulated genes where they may serve to facilitate the HMG-I/Y-mediated displacement of histone H1 in chromatin. Indeed, HMG-I/Y was found to be strongly enriched in the H1-depleted subfraction which can be isolated from chromatin. PMID- 8344263 TI - Complementation between HIV integrase proteins mutated in different domains. AB - HIV integrase (IN) cleaves two nucleotides off the 3' end of viral DNA and integrates viral DNA into target DNA. Previously, three functional domains in the HIV IN protein have been identified: (i) the central catalytic domain, (ii) the C terminal DNA binding domain, and (iii) the N-terminal region, which is also necessary for activity. We have now investigated whether IN proteins mutated in different domains can complement each other. Mutant D116I does not contain an intact active site, but does bind DNA, whereas the C-terminal deletion mutant C delta 73 does not bind DNA, but does have an intact active site. Neither mutant protein mediates site-specific cleavage or integration. However, a mixture of both proteins is active, suggesting that IN functions as an oligomer, and that two subunits can have different functions; one subunit binds the (viral) DNA and another subunit provides the active site. We found three classes of mutants, corresponding to the three domains mentioned above. Mutants from different classes, but not from the same class, can complement each other. However, complementation is most efficient when the N- and C-termini are present on the same molecule. PMID- 8344262 TI - Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. AB - Chromatin organization of eukaryotic promoters is increasingly recognized as an important factor in the regulation of transcription in vivo. To determine the role of chromatin in HIV-1 expression, we have examined the nucleosome organization of the promoter of HIV-1 under low and high transcription rates. Independently of the cell line examined, nucleosomes are precisely positioned in the viral 5' long terminal repeat (5' LTR) and define two large nucleosome-free regions encompassing nt 200-450 and 610-720. A nucleosome positioned between these two regions, immediately after the transcription initiation site (nuc-1), is disrupted following TPA or TNF-alpha treatment. The disruption of nuc-1 from DNA is independent of DNA replication since it is completed in 20 min and independent of transcription as it is alpha-amanitin insensitive. A model is proposed in which nuc-1 plays an organizing role in the HIV-1 promoter to bring in close proximity factors bound to DNA in the two nucleosome-free regions, upstream and downstream of the site of transcription initiation. These results define chromatin as an integral component of the HIV-1 transcriptional regulatory machinery and identify a chromatin transition associated with activation of viral gene expression. PMID- 8344264 TI - Identification of discrete functional domains of HIV-1 integrase and their organization within an active multimeric complex. AB - HIV-1 integrase protein possesses the 3' processing and DNA strand transfer activities that are required to integrate HIV DNA into a host chromosome. The N-, C-terminal and core domains of integrase are necessary for both activities in vitro. We find that certain pairs of mutant integrase proteins, which are inactive when each protein is assayed alone, can support near wild type levels of activity when both proteins are present together in the reaction mixture. This complementation implies that HIV-1 integrase functions as a multimer and has enabled us to probe the organization of the functional domains within active mixed multimers. We have identified a minimal set of functional integrase domains that are sufficient for 3' processing and DNA strand transfer and find that some domains are contributed in trans by separate monomers within the functional complex. PMID- 8344265 TI - Homologous recombination-dependent initiation of DNA replication from DNA damage inducible origins in Escherichia coli. AB - Escherichia coli cells induced for the SOS response express inducible stable DNA replication (iSDR) as an SOS function. Initiation of iSDR is independent of transcription, translation and DnaA protein, which are essential for initiation of DNA replication from oriC. We found that a recA mutant that is defective in recombination but proficient in SOS induction could not elicit iSDR. In contrast, iSDR was enhanced by recD and recJ mutations that inactivate the exonuclease V activity of the RecBCD enzyme and the RecJ exonuclease activity, respectively. A mutation in the ruvC gene that blocks the resolution of recombination intermediates (i.e. Holliday structures) also enhanced iSDR. Furthermore, inhibition of branch migration by recG or ruvAB mutations dramatically increased the iSDR activity. recBC mutants are defective in iSDR induction but the defect was suppressed by a mutation in the sbcA gene. The major product of minichromosomes replicated by iSDR was covalently closed circular monomers. We propose that recombination intermediates (i.e. D-loop structures) created by the action of RecA recombinase and RecBC(D) helicase play a central role in initiation of iSDR. PMID- 8344266 TI - Molecular dissection of the cauliflower mosaic virus translation transactivator. AB - The cauliflower mosaic virus (CaMV) transactivator (TAV) is a complex protein that appears to be involved in many aspects of the virus life cycle. One of its roles is to control translation from the polycistronic CaMV 35S RNA. Here we report a molecular dissection of TAV in relation to its ability to enhance dicistronic translation in transient expression experiments. We have identified a protein domain that is responsible and sufficient for that activity. This 'MiniTAV domain' consists of only 140 of the 520 amino acids in the full-length sequence. A further domain located outside the MiniTAV, and therefore dispensable for transactivation, is probably involved in interactions with other molecules. This was identified by its ability to compete with wild-type TAV and some of its deletion mutants. We found, furthermore, that the TAV protein binds RNA. Two regions needed for RNA-binding properties were defined outside the MiniTAV domain and RNA binding seems not to be directly involved in the transactivation mechanism. PMID- 8344267 TI - Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. AB - We investigated the requirements for selenocysteine insertion at single or multiple UGA codons in eukaryotic selenoproteins. Two functional SECIS elements were identified in the 3' untranslated region of the rat selenoprotein P mRNA, with predicted stem-loops and critical nucleotides similar to those in the SECIS elements in the type I iodothyronine 5' deiodinase (5'DI) and glutathione peroxidase selenoprotein mRNAs. Site-directed mutational analyses of three SECIS elements confirmed that conserved nucleotides in the loop and in unpaired regions of the stem are critical for activity. This indicates that multiple contact sites are required for SECIS function. Stop codon function at any of five out-of context UGA codons in the 5'DI mRNA was suppressed by SECIS elements from the 5'DI or selenoprotein P genes linked downstream. Thus, the presence of SECIS elements in eukaryotic selenoprotein mRNAs permits complete flexibility in UGA codon position. PMID- 8344268 TI - Yeast prt1 mutations alter heat-shock gene expression through transcript fragmentation. AB - The inhibition of translation initiation by modification or mutation of initiation factors can lead to disproportionate effects on gene expression. Here we report disproportionate decreases in gene expression in cells with mutated Prt1 activity. The PRT1 gene product of the budding yeast Saccharomyces cerevisiae is necessary for translation initiation and is thought to be a component of initiation factor 3. At a restrictive temperature the prt1-1 mutation, in addition to decreasing global protein synthesis, caused disproportionate decreases of the synthesis of the Ssa1 and Ssa2 members of the hsp70 heat-shock gene family, and of the Hsp82 and Hsc82 heat-shock proteins. Quantification of pulse-labelled, immunoprecipitated lacZ fusion proteins showed that synthesis of each of these proteins was disproportionately decreased in prt1 1 mutant cells. Although the mRNAs of affected genes were shown to be polysomal in mutant cells, they were fragmented and of decreased abundance, as indicated by transcript analysis and in vitro translation. Thus the mRNAs of these hsp genes become degraded under the conditions of limited translation initiation that are imposed by the prt1-1 mutation. This untimely mRNA degradation accounts for the disproportionate decreases in polypeptide synthesis in prt1 mutant cells. We propose that sequences at the translation initiation site of SSA2 mRNA bring about the observed mRNA fragmentation. PMID- 8344269 TI - Identity determinants of human tRNA(Ser): sequence elements necessary for serylation and maturation of a tRNA with a long extra arm. AB - Recently, there has been much progress in understanding tRNA identity, i.e. in elucidating the sets of nucleotides that are responsible for the specific aminoacylation of a tRNA with its cognate amino acid. Interest focused, however, on tRNAs from Escherichia coli and yeast. Here we have identified the major and minor determinants of human tRNA(Ser) which were revealed by an identity switch from human tRNA(Val) to tRNA(Ser). We used in vitro transcripts and subsequent aminoacylation by HeLa S100 extract to determine the kinetic parameter Vmax/Km. The two major identity elements which are absolutely required for aminoacylation by human seryl-tRNA synthetase are the discriminator base and the long extra arm. This is in contrast to E. coli tRNA(Ser) where the discriminator base is unimportant, whereas identity determinants in the acceptor stem are required. Other sequence elements have an influence not only on serylation, but also on tRNA maturation in vitro, i.e. on pre-tRNA processing and base modification. These nucleotides are located in the DHU and the T phi C arm and are probably necessary for the proper folding of tRNAs containing a long extra arm. A34 to inosine modification depends highly on the correct three-dimensional structure of the tRNA, whereas A58 to m1A methylation does not rely on the three-dimensional folding of the substrate. This is the first tRNA identity switch involving the exchange of a short versus a long extra arm. PMID- 8344271 TI - 5-lipoxygenase-activating protein stimulates the utilization of arachidonic acid by 5-lipoxygenase. AB - 5-Lipoxygenase (5-LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5-LO catalyzing both the synthesis of (5S)-5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5-HPETE. We have previously expressed both human 5-LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5-LO, we compared cellular 5-LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5-LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5-LO as a substrate, and increases the efficiency with which 5-LO converts 5-HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5-LO is inhibited by 3-[1-(p chlorophenyl)-5-isopropyl-3-tert-butylthio-1H-indol-2-yl]-2,2- dimethyl-propanoic acid (MK-886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5-LO by acting as an arachidonic acid transfer protein. PMID- 8344270 TI - In vivo reactivation of catechol 2,3-dioxygenase mediated by a chloroplast-type ferredoxin: a bacterial strategy to expand the substrate specificity of aromatic degradative pathways. AB - The meta-cleavage operon of the TOL plasmid pWW0 of Pseudomonas putida contains 13 genes responsible for the oxidation of benzoate and toluates to Krebs cycle intermediates via estradiol (meta) cleavage of (methyl)catechol. The functions of all the genes are known with the exception of xylT. We constructed pWW0 mutants defective in the xylT gene, and found that these mutants were not able to grow on p-toluate while they were still capable of growing on benzoate and m-toluate. In the xylT mutants, all the meta-cleavage enzymes were induced by p-toluate with the exception of catechol 2,3-dioxygenase whose activity was 1% of the p-toluate induced activity in wild-type cells. Addition of 4-methylcatechol to m-toluate grown wild-type and xylT cells resulted in the inactivation of catechol 2,3 dioxygenase in these cells. In the wild-type strain but not in the xylT mutant, the catechol 2,3-dioxygenase activity was regenerated in a short time. The regeneration of the catechol 2,3-dioxygenase activity was also observed in H2O2 treated wild-type cells, but not in H2O2-treated xylT cells. We concluded that the xylT product is required for the regeneration of catechol 2,3-dioxygenase. PMID- 8344272 TI - A high-order structure of plant storage proprotein allows its second conversion by an asparagine-specific cysteine protease, a novel proteolytic enzyme. AB - During seed embryogenesis, glycinin, the 11-S seed storage protein found in soybeans, undergoes post-translational proteolytic processing, in which a proprotein molecule is cleaved into an acidic and a basic subunit by a one-point cleavage that occurs at the carboxyl side of the asparaginyl residue located at the junction of the subunits. To elucidate the mechanism of this very limited proteolysis, we purified the cysteine endoprotease and used purified proglycinin produced by Escherichia coli as a substrate. This enzyme was separated by isoelectric focusing into three isomeric forms: two had a molecular mass of 33 kDa and the third, 33.8 kDa. The cysteine protease was found both in the proteinaceous vacuoles of cotyledonary tissue of immature seeds and in mature seeds, and is the first proteolytic enzyme to be classified as an asparagine specific endoprotease. The results also indicate that the above proteolysis is largely attributable to the conformational accessibility of the enzyme to the asparaginyl residue in the cleavage site of proglycinin. The conformation of this single enzyme-accessible region on the proglycinin molecule is relatively flexible and becomes unstable under low salt conditions, or when heat is applied, causing the enzyme to lose its specificity. PMID- 8344274 TI - Interaction of type IV collagen with the isolated integrins alpha 1 beta 1 and alpha 2 beta 1. AB - The triple-helical cyanogen-bromide-derived fragment CB3[IV] of collagen IV, located 100 nm from the N-terminus of the molecule, contains the binding sites for the integrins alpha 1 beta 1 and alpha 2 beta 1. To investigate the interaction of these integrins and collagen IV, we performed solid-phase and inhibition assays using as receptor isolated alpha 1 beta 1 and alpha 2 beta 1. The ligands used were the binding-site-bearing trimeric peptide CB3[IV] and its shorter tryptic fragments F1-F4. Using titration curves, in which the binding of soluble receptors to coated ligands and the binding of soluble ligands to coated receptors were analyzed, the binding sites for alpha 1 beta 1 and alpha 2 beta 1 were in different but adjacent areas of CB3[IV]. Triple-helical conformation and distinct primary structures were required for the interaction. Dissociation constants (Kd), for the affinity of integrins for collagen IV, were determined in the 1-nM range in the presence of Mn2+ and Mg2+. In the absence of Mn2+, the Kd values indicated a 30-60-fold decrease in the affinities, which for alpha 2 beta 1 was further reduced by adding Ca2+. In the presence of Ca2+ and Mg2+ the affinity of collagen IV for alpha 1 beta 1 was four-times higher than for alpha 2 beta 1. PMID- 8344273 TI - Cell-cell adhesion by homophilic interaction of the neuronal recognition molecule axonin-1. AB - The axonal surface glycoprotein axonin-1, which occurs both as a glycosyl phosphatidylinositol-anchored membrane-bound form and a secreted form, promotes neurite outgrowth and is thought to be involved in axon-guidance mechanisms in the developing nervous system. Recently, we have demonstrated that the neurite outgrowth-promoting activity of axonin-1, presented as a substratum for cultured neurons, is mediated by a heterophilic interaction with the axonal glycoprotein neuronglia cell-adhesion molecule (Ng-CAM). Here we present evidence for homophilic (like-like) binding among axonin-1 molecules. Axonin-1 was heterologously expressed in myeloma cells. Clonal cell lines, with exposed membrane-bound axonin-1 at their surface, formed large multicellular aggregates. Incubations of transfected and parental myeloma cells, under a series of different conditions, revealed homophilic axonin-1/axonin-1 interactions across the intermembrane space as the molecular mechanism promoting stable cell-cell contacts. Using structural and functional characterisation, recombinant axonin-1 was very similar to native axonin-1, suggesting that homophilic axonin-1 interactions are also established in neurons. The capability of axonin-1 to interact with both Ng-CAM and other axonin-1 molecules might contribute to the formation of macromolecular networks at contact sites of growth cones and axons, comprising molecules of both membranes, and thus represent a mechanism for regulating neurite outgrowth and pathfinding. PMID- 8344275 TI - Synthesis of 3-arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia-lyase. Comparison with arsenical analogues of malate and fumarate. AB - DL-3-Arsonoalanine has been synthesized by the Strecker synthesis from the unstable compound arsonoacetaldehyde. It inactivates pig heart cytosolic aspartate aminotransferase and inhibits aspartate ammonia-lyase by competing with aspartate (Ki/Km 0.23). The fumarate analogue (E)-3-arsonoacrylic acid and the malate analogue (RS)-3-arsonolactate also inhibit fumarate hydratase, competing with fumarate (Ki/Km 1.8) and malate (Ki/Km 1.6) respectively. Attempted non enzymic transamination of 3-arsonoalanine gave elimination of arsenite, in contrast with the transamination of 3-phosphonoalanine, which is either successful or leads to loss of phosphate. PMID- 8344276 TI - Increase of specificity of RNase from Bacillus amyloliquefaciens (barnase) by substitution of Glu for Ser57 using site-directed mutagenesis. AB - Bacterial ribonucleases from Bacillus amyloliquefaciens and Bacillus intermedius show the specificity towards the nature of a nucleoside at the O3' end of the phosphodiester bond to be split in the preference order G > A >> U > C in the cleavage reactions of polynucleotides. It follows from the X-ray data that the substrate guanosine base is bound at the active site of these RNases in the same manner as for high-specificity guanylic RNases. We supposed that the difference in specificity for the two types of RNases is due to the additional hydrogen bond between the protein and a purine base in the case of bacterial guanyl-preferring RNases in contrast to the high-specificity guanylic RNases. To examine this hypothesis we prepared the Ser57 --> Glu mutant of B. amyloliquefaciens, in which this hydrogen bond is eliminated. Kinetic studies demonstrate that the specificity of this mutant towards guanylic substrates is 35-times greater than that of the wild-type RNases from B. amyloliquefaciens and close to that of RNases T1. PMID- 8344277 TI - Localization of two myosin-subfragment-1 binding contacts in the 96-132 region of actin subdomain-1. AB - Many direct observations and indirect experimental approaches have pin-pointed two segments (sequences 1-28 and 360-372) in actin subdomain-1 which bind to myosin subfragment-1. In a previous investigation [Labbe, J. P., Mejean, C., Benyamin, Y. & Roustan, C. (1990) Biochem. J. 271, 407-413], we have observed competition between myosin subfragment-1 and anti-actin antibodies specific to epitopes including Thr103. A multisite interface model has also been proposed to take into account myosin-head binding to the N-terminal and C-terminal regions and to more central 40-113 sequence of actin. In the present study, two limited actin segments encompassing residues 96-103 and 112-125 were identified as myosin head-binding sites. Myosin subfragment-1 competed for monomeric actin with the antibodies directed against sequences 96-105 and 114-120 and its binding to the tryptic 96-113 and synthetic 112-125 actin peptides was prevented by magnesium pyrophosphate but not by calcium pyrophosphate. In the presence of ATP-Mg2+, myosin subfragment-1 was dissociated by filamin from its complex with monomeric actin or with peptide 105-120. Contact points of filamin on actin were previously located in the 105-120 and 360-372 actin sequences [Mejean, C., Lebart, M. C., Boyer, M., Roustan, C. & Benyamin, Y. (1992) Eur. J. Biochem. 209, 555-562]. The in vitro inhibitory effect of filamin on actin-activated Mg2+-ATPase would thus be explained by this competition. Furthermore, the (27-kDa-50-kDa-20-kDa) trypsin split myosin subfragment-1 which could no longer be activated by actin, did not bind at all to the two sites located in the 96-125 region, but it still interacted with the 360-372 segment. Our results regarding the position of the myosin head on actin monomers in rigor conditions provide evidence on the presence of two topologically independent contact points in the myosin-head/actin interface. One group exposed residues in the 1-7, 21-29, 77-95 and 96-103 actin segment, another, on the opposite side of subdomain-1, included residues from 112 125 and 360-372 sequences. PMID- 8344278 TI - Structural study of the oligosaccharide moieties of sphingolipid activator proteins, saposins A, C and D obtained from the spleen of a Gaucher patient. AB - We have determined and compared the structures of the oligosaccharide moieties of saposin A, C and D purified from the spleen of a patient with Gaucher disease. These saposins, together with saposin B, are small glycoproteins, derived from separate domains of a single precursor, prosaposin, and are required for the lysosomal hydrolysis of various sphingolipids. The characteristic features of the oligosaccharide moieties of saposin A are (a) the predominance of a fucosylated trimannosyl core structure and (b) the occurrence of several different oligomannose-type and N-acetyllactosamine-type oligosaccharides. Saposin C contains (a) a predominance of oligomannose-type oligosaccharides and monoantennary oligosaccharides and (b) the presence of four different oligosaccharides having bisecting N-acetylglucosamine residues (found only in this saposin). Saposin D is distinguished by the occurrence of oligomannose-type oligosaccharides, which comprise nearly 90% of its total oligosaccharides. The possible reasons for the unique glycosylation of each saposin is discussed. PMID- 8344279 TI - Rapid dephosphorylation of microtubule-associated protein 2 in the rat brain hippocampus after pentylenetetrazole-induced seizures. AB - We have studied the effect of Pentylenetetrazole (PTZ)-induced seizures on the state of phosphorylation of microtubule-associated protein 2 (MAP-2) from rat hippocampus. A method for the in vivo 32P-labeling of hippocampal proteins has been established, consisting of intracerebro-ventricular injection of 32PO4 of high specific activity. The results obtained indicate that PTZ induces a rapid and transient dephosphorylation of high-molecular-mass MAP-2, which is prevented when the N-methyl-D-aspartate receptor antagonist MK-801 is previously administered. Phosphopeptide mapping of 32P-labeled MAP-2 obtained from hippocampi of PTZ-treated rats reveals a pattern of phosphorylation distinct from that obtained from control saline-treated rats or MK-801 plus PTZ treated rats. We discuss the possible implications of N-methyl-D-aspartate-receptor activation and MAP-2 dephosphorylation on the plastic changes induced in rat brain hippocampus after induced epileptiform activity. PMID- 8344280 TI - Biosynthesis and secretion of human interleukin 2 glycoprotein variants from baculovirus-infected Sf21 cells. Characterization of polypeptides and posttranslational modifications. AB - Human interleukin 2 (IL-2) and human IL-2 mutant proteins, with artificially introduced N-glycosylation or O-glycosylation sites, have been expressed in a lepidopteran cell line (Sf21, Spodoptera frugiperda) using recombinant baculovirus vectors. Only approximately 25% of the total recombinant IL-2 protein synthesized by Sf21 cells was secreted into the culture medium. Significant N terminal truncations were detected in the secreted polypeptides (up to 85% of the molecules). Alanine and proline were absent in the major truncated forms; the first 3-5 amino acids were also absent in a small proportion of the purified proteins. The introduction of potential artificial O-glycosylation peptide sequences (..GGKAPTPPPK..), to the C-terminus or between positions 80 and 81 of the IL-2 polypeptide chain, resulted in the secretion of unglycosylated and O glycosylated variant forms. Fast atom bombardment mass spectrometry, compositional analysis and methylation analysis, of the tryptic glycopeptide APTPPPK, revealed the presence of either GalNAc or the disaccharide Gal(beta 1 3)GalNAc as the only carbohydrate constituents attached exclusively to Thr in this peptide, in a specific ratio for each individual IL-2 mutant protein. The Gal(beta 1-3)GalNAc protein forms could be partially altered in vitro to mammalian-type glycoforms by porcine liver beta-galactoside alpha-2,3 sialyltransferase in the presence of CMP-N-acetylneuraminic acid. An IL-2 mutant form, with an 11-amino-acid peptide of human interferon-beta at position 4, which includes its only N-glycosylation site, had exclusively truncated proximally fucosylated oligomannosidic glycans; Man3GlcNAc[Fuc(alpha 1-6)]GlcNAc or Man2GlcNAc[Fuc(alpha 1-6)]GlcNAc structures, in a ratio of 3:1, were detected in the secreted proteins. No evidence was obtained for the presence of secreted proteins with complex oligosaccharide chains, irrespective of the cell-culture conditions used or the harvesting time, for infected cells with recombinant baculovirus constructs. PMID- 8344281 TI - The existence of two mitochondrial isoforms of 2,4-dienoyl-CoA reductase in the rat. AB - Isoforms of 2,4-dienoyl-CoA reductase (EC 1.3.1.34), which is the key enzyme in the beta-oxidation of fatty acids with double bonds, have been studied in rat heart and liver. Electrofocusing and adsorption chromatography on hydroxyapatite were used to separate the reductase activity in tissue homogenates into two peaks, one peak in each experiment being identified as the previously purified mitochondrial reductase. The novel activity was partially purified from rat liver by means of ammonium sulphate precipitation, anion-exchange chromatography on DEAE-cellulose (DE-52), hydrophobic chromatography on Phenyl-Sepharose and dye ligand binding chromatography (Blue Sepharose). Taking into account the contribution of the different reductases to the total activity in rat liver, the overall purification for the novel isoform was 1900-fold. Ultracentrifugation on a sucrose gradient gave an M(r) of 50,000 and size-exclusion chromatography on Superdex 200 an M(r) of 60,000. The antibody against the previously characterised reductase did not cross-react with this novel isoform, but the distribution of the activity peaks in heart and liver tissue, and an electrofocusing experiment with isolated mitochondria, both pointed to a mitochondrial origin. The novel reductase was estimated to account for 80% (50%) of the total reductase activity in rat heart (liver) homogenate measured with 2,4-hexadienoyl-CoA. The present results, together with those previously published, suggest that mammals have at least three reductase isoforms: two in mitochondria and a third one in peroxisomes, but the peroxisomal activity has not been characterised so far. PMID- 8344282 TI - X-ray and primary structure of horse serum albumin (Equus caballus) at 0.27-nm resolution. AB - The amino-acid sequence and three-dimensional structure of equine serum albumin have been determined. The amino-acid sequence was deduced from cDNA isolated from equine liver. Comparisons of the primary structure of equine serum albumin with human serum albumin and bovine serum albumin reveal 76.1% and 73.9% sequence identity, respectively. The three-dimensional structure was determined crystallographically by the molecular-replacement method using molecular coordinates from the previously determined structure of human serum albumin, to a resolution of 0.27 nm. In accordance with the primary structure, the three dimensional structures are highly conserved. There is a root-mean-square difference between alpha-carbons of the two structures of 0.201 nm. The association constants (Ka) for the binding of 2,3,5-triiodobenzoic acid were determined by ultrafiltration methods for equine and human serum albumins to be approximately 10(4) M-1 and 10(5) M-1, respectively. Crystallographic studies of equine serum albumin reveal two binding sites for 2,3,5-triiodobenzoic acid identical with those previously reported for human serum albumin which are located within subdomains in IIA and IIIA. Details and comparisons of the binding chemistry are discussed. PMID- 8344284 TI - Equilibrium and transient kinetic studies of the binding of cytochalasin B to the L-arabinose-H+ symport protein of Escherichia coli. Determination of the sugar binding specificity of the L-arabinose-H+ symporter. AB - The kinetics of the binding of cytochalasin B to the L-arabinose-H+ symport protein of Escherichia coli have been investigated, using a strain that over produces the symport protein in the cytoplasmic membrane. Equilibrium binding studies revealed a single set of binding sites (2.9-8.9 nmol/mg protein) with a Kd of 0.7-1.0 microM at 22 degrees C. It proved possible to follow the transient kinetics of cytochalasin B binding by measuring the changes in the fluorescence of the L-arabinose-H+ symporter upon binding the ligand, by stopped-flow fluorescence spectroscopy. The association and dissociation rate constants thus determined were confirmed by rapid filtration measurements, using [3H]cytochalasin B, yielding values of 4.5-6.5 microM-1.s-1 and 4-5 s-1, respectively, consistent with Kd values obtained by measuring equilibrium binding of [3H]cytochalasin B by dialysis at 22 degrees C. Titration of the protein fluorescence with cytochalasin B yielded a similar binding site concentration and Kd value to those obtained in equilibrium binding studies. All the measurements of binding site concentration are consistent with a stoichiometry of 1 mol cytochalasin B binding sites/mol L-arabinose-H+ symport protein. Inhibition of both the rate and equilibrium binding of cytochalasin B by sugars indicated the following order of substrate binding 5-thio-D-glucose > D-fucose > L-arabinose > 6-deoxy-6-fluoro-D-galactose > D-xylose approximately 6-deoxy-D-glucose > D galactose > D-glucose > D-ribose. Neither D-arabinose nor L-fucose had any significant inhibitory effect upon cytochalasin B binding. PMID- 8344283 TI - Effect of bromoconduritol on glucosidase II from rat liver. A new kinetic model for the binding and hydrolysis of the substrate. AB - Bromoconduritol inhibits the p-nitrophenyl-glucosidase and maltase activities of glucosidase II purified from rat liver, an enzyme that removes the two alpha-1,3 linked glucose residues of the protein-bound oligosaccharide Glc2Man9GlcNAc2 in the processing of N-glycoproteins. The inactivation process exhibits pseudo-first order kinetics. Previously, we have demonstrated the occurrence of two binding (active) sites in the glucosidase II for the substrates p-nitrophenyl alpha-D glucopyranoside (pNphGlc) and maltose (high- and low-affinity sites). The inhibition kinetic studies with bromoconduritol indicate that the high- and low affinity sites for pNphGlc correspond to high- and low-affinity sites for maltose, respectively. Bromoconduritol has no effect on the binding of the substrates (pNphGlc and maltose) to the high-affinity site, although it does modify the low-affinity site and hinders the binding of the two indicated substrates to this site. These results, together with previous reports, have prompted us to propose a new kinetic model of binding and hydrolysis of the physiological substrate of the enzyme, in which the outermost glucose residue would bind and be released at the high-affinity site, whereas the innermost glucose residue would do so at the low-affinity site. PMID- 8344285 TI - Structural change of jack bean urease induced by addition of surfactants studied with synchrotron-radiation small-angle X-ray scattering. AB - Both the quaternary and subunit structures of jack bean urease in solutions with ionic and nonionic surfactants have been studied by small-angle X-ray scattering using a synchrotron-radiation source. The effects of those surfactants on the enzyme activity of urease have also been investigated in the same kind of solvent systems as those used for the scattering experiments. The present results show that the quaternary structure of urease in solution is fairly elongate and that by the relatively minor binding of SDS (SDS/protein = 0.23/1) the native urease molecule is dissociated into six identical subunits with nearly spherical structures. In addition the enzyme activity of urease was mostly retained under every solvent condition investigated, indicating that the subunit found in the present scattering experiments is the fundamental monomeric unit for both the quaternary-structure formation and enzyme function of urease. PMID- 8344286 TI - Characterization of a marsupial sperm protamine gene and its transcripts from the North American opossum (Didelphis marsupialis). AB - A synthetic oligonucleotide primer, designed from marsupial protamine protein sequence data [Balhorn, R., Corzett, M., Matrimas, J. A., Cummins, J. & Faden, B. (1989) Analysis of protamines isolated from two marsupials, the ring-tailed wallaby and gray short-tailed opossum, J. Cell. Biol. 107] was used to amplify, via the polymerase chain reaction, protamine sequences from a North American opossum (Didelphis marsupialis) cDNA. Using the amplified sequences as probes, several protamine cDNA clones were isolated. The protein sequence, predicted from the cDNA sequences, consisted of 57 amino acids, contained a large number of arginine residues and exhibited the sequence ARYR at its amino terminus, which is conserved in avian and most eutherian mammal protamines. Like the true protamines of trout and chicken, the opossum protamine lacked cysteine residues, distinguishing it from placental mammalian protamine 1 (P1 or stable) protamines. Examination of the protamine gene, isolated by polymerase-chain-reaction amplification of genomic DNA, revealed the presence of an intron dividing the protamine-coding region, a common characteristic of all mammalian P1 genes. In addition, extensive sequence identity in the 5' and 3' flanking regions between mouse and opossum sequences classify the marsupial protamine as being closely related to placental mammal P1. Protamine transcripts, in both birds and mammals, are present in two size classes, differing by the length of their poly(A) tails (either short or long). Examination of opossum protamine transcripts by Northern hybridization revealed four distinct mRNA species in the total RNA fraction, two of which were enriched in the poly(A)-rich fraction. Northern-blot analysis, using an intron-specific probe, revealed the presence of intron sequences in two of the four protamine transcripts. If expressed, the corresponding protein from intron-containing transcripts would differ from spliced transcripts by length (49 versus 57 amino acids) and would contain a cysteine residue. PMID- 8344288 TI - Purification and characterization of guinea pig gastric phospholipase A2 of the pancreatic type. AB - Guinea pig gastric mucosa and juice contained exceptionally high phospholipase-A2 activity, whereas the activity in the pancreas was only minimal. Phospholipases A2 were purified to homogeneity from these three tissues. Structural evidence, including the sequence of the NH2-terminal 41 residues, the amino-acid composition and the molecular mass (13902 +/- 3 Da) determined accurately by mass spectrometry, showed that the gastric mucosa enzyme belongs to the pancreatic type. An unique feature of the sequence is the substitution of Phe for the hitherto invariant Tyr28 in the calcium-binding loop of pancreatic phospholipases A2. The affinity of the guinea pig enzyme for Ca2+ in the presence of substrate was, however, identical to that of the rat enzyme with Tyr28, suggesting the interaction of a phenolic hydroxyl group of the Tyr with its neighboring residues is not significantly linked to the binding of Ca2+. The NH2-terminal sequences and immunochemical properties of the enzymes purified from the gastric juice and pancreas were identical to those of the gastric mucosa enzyme. The distribution of cells immunoreactive with anti-(gastric PLA2) immunoglobulin in the stomach was quite similar to that of the chief cells. Unlike in pancreas of other animals, the prophospholipase A2 was not detectable in gastric mucosa or juice homogenates treated with diisopropyl fluorophosphate or in column effluents during purification under acidic conditions. An appreciable prophospholipase-A2 activating activity was not detectable in gastric mucosa extracts at low pH relevant to gastric juice, using rat prophospholipase A2 as substrate. This opposes the activation of secreted proenzyme in the gastric juice. PMID- 8344287 TI - The US-1 element from the gene encoding rat poly(ADP-ribose) polymerase binds the transcription factor Sp1. AB - By comparing the upstream DNA sequence of the rat and human genes encoding poly(ADP-ribose) polymerase (PARP), we have defined a 16-bp conserved region and designated it as US-1 for 'upstream sequence 1'. This element is homologous to the recently described binding site for the transcription factor Sp1 in the promoter sequence of the mouse p12 gene which encodes a protease inhibitor. Analyses in gel mobility shift assays revealed that a nuclear protein, produced by all tissue-culture cells tested, specifically binds the US-1 element. The pattern of shifted DNA protein complexes obtained was strikingly similar to that for Sp1, which is supported by the positive displacement of these complexes by an oligomer containing the Sp1 binding site in gel shift competition experiments. Replacement of the Sp1 binding site from the basal promoter of the mouse p12 gene by the rPARP US-1 element did not result in any significant variations in the level of expression of the chloramphenicol acetyltransferase (CAT) reporter gene upon transient transfection of tissue-culture cells. However, when point mutations are introduced in the US-1 element in a similar substitution experiment, a significant reduction in CAT gene expression could be observed. These data are consistent with Sp1 interacting with the US1 element. Results from DNase I footprinting experiments clearly indicated that purified Sp1 not only binds to the US-1 element but also to four other closely located cis-acting sites scattered in the promoter of the rat PARP gene, therefore suggesting that Sp1 is likely to modulate strongly the expression of that gene in different tissues. PMID- 8344289 TI - A study of the binding of NADP coenzymes to dihydrofolate reductase by raman difference spectroscopy. AB - We report here the Raman spectra of NADPH, NADP+, 3-acetylpyridine adenine dinucleotide (AcPdADP+), NADH and a fragment of these molecules, 2'-phospho adenosine-5'-diphosphoribose (Ado2'p5'ppRib), bound to Escherichia coli dihydrofolate reductase (DHFR). The positions that are observed for the bound adenosine 'triplet' bands are consistent with a protein binding pocket for this group which is quite hydrophobic in nature. No binding effect is observed on Raman bands associated with the nicotinamide group of NADP+ as a binary complex with DHFR, suggesting very loose, if any, binding of this group. In contrast, changes in the Raman spectrum of the nicotinamide group of NADP+ bound to an inhibitor (trimethoprim) ternary complex of DHFR are clearly observed which indicate substantial binding interaction. The carboxamide group of bound NADPH (and NADH) adopts the trans conformation. A 35-cm-1 upshift is observed in the rocking motion of the carboxamide -NH2 group of NADPH, and a 5-cm-1 upward shift is seen in the C=O stretch mode of AcPdADP+ upon binding to the enzyme trimethoprim complex. These results suggest that the -NH2 group of the carboxamide moiety is more tightly hydrogen bonded in the protein binding pocket than in solution while that of the C=O group is less tightly hydrogen bonded; these hydrogen bonds would appear to be responsible for holding the nicotinamide headgroup in place properly for catalysis. We have compared this with the results obtained previously in other protein complexes, and interpret the observed shifts in these bands as a measure of the hydrogen bonding enthalpy of the -NH2 and C=O groups with their protein environments. Perhaps surprisingly, the magnitude of the hydrogen bonding enthalpy takes on a limited number of discrete values over five protein complexes rather than over a continuous range. The effect that this has on the catalytic properties of DHFR and the other NAD dehydrogenases that we have studied to date, particularly their stereochemistry, is discussed. A small downward shift is observed for the P = O stretch of the 2'-phosphate moiety of NADP. This indicates that the 2'-phosphate moiety binds to DHFR in the dianionic form. Furthermore, the local enthalpic interaction that the 2'-phosphate group has with protein is stronger than its interaction with water. PMID- 8344290 TI - Cloning and expression of phospholipase A2 from guinea pig gastric mucosa, its induction by carbachol and secretion in vivo. AB - A cDNA encoding phospholipase A2 (PLA2) was cloned from guinea pig gastric mucosa using a rat pancreatic-PLA2-cDNA fragment as a probe. The cDNA contains an open reading frame sufficient to encode the entire amino-acid sequence of a PLA2 precursor protein consisting of 146 amino acids, including a putative 16-residue signal peptide and a 6-residue activation peptide at the NH2-terminus. Its nucleotide sequence exhibits 70% similarity to that of rat pancreatic PLA2 cDNA. The deduced amino-acid sequence has all the typical pancreatic PLA2 characteristics, with the exception of the substitution of Phe for Tyr at position 28 in the calcium-binding loop of the mature enzyme. When an expression vector containing the PLA2 cDNA was transfected into COS-7 cells, a major portion of the proenzyme was secreted into the culture medium. Northern-blot analysis showed the mRNA was present in guinea pig lung and pancreas at much lower levels than in the stomach. The effect of carbachol, a muscarinic acetylcholine agonist, on the secretion of gastric PLA2 and on its mRNA level in the gastric mucosa were examined. PLA2 secretion into the gastric juice was maximal 30 min after the subcutaneous administration of carbachol (0.4 mg/kg). It also increased the PLA2 mRNA level in the tissue, the maximal mRNA level being delayed about 15 min compared with that in PLA2 secretion. These results suggest that vagal stimuli may contribute to PLA2 secretion and its compensatory synthesis, and that the secreted PLA2 may participate in the digestion of dietary and biliary phospholipids in the small intestine of guinea pig. PMID- 8344291 TI - Isolation, characterization and expression of the eclosion hormone gene of Drosophila melanogaster. AB - Eclosion hormone (EH) is a neuropeptide that triggers the performance of ecdysis behaviors at the end of a molt. We have isolated the EH gene from Drosophila melanogaster, and localized the gene to the right arm of chromosome 3 at band position 90B1-2. The 97-amino-acid translation product contains a signal peptide followed by a 73-amino-acid prohormone. The N-terminus of the prohormone has diverged from lepidopteran EH both in its length and amino acid composition, and contains a potential endoproteolytic cleavage site. The deduced sequence of Drosophila EH is 58% identical (36 of 62 amino acids) to that of Manduca EH. The EH gene is expressed as a 0.8-kb transcript in a single pair of brain neurons which extend their processes the entire length of the central nervous system and also to the corpora cardiaca portion of the ring gland. These cells show massive depletion of immunoreactive EH at ecdysis. PMID- 8344292 TI - Lipase from Pseudomonas aeruginosa. Production in Escherichia coli and activation in vitro with a protein from the downstream gene. AB - The lipase gene from Pseudomonas aeruginosa TE3285 is followed by another gene, lipB. The lipase gene was expressed in Escherichia coli BL21(DE3)pLysS using the T7 RNA polymerase expression system. The mature lipase was accumulated as inclusion bodies at 42% of the total cell proteins. The inclusion bodies were solubilized with 8 M urea, but lipase activity was not detected in the solubilized preparation containing 85% lipase protein even after removing urea by dialysis. The lipB gene, positioned downstream of the lipase gene and thought to be necessary for the expression of the lipase gene, was expressed in Escherichia coli JM109 as a fusion with the glutathione transferase gene from Schistosoma japonicum. The fusion protein was partially purified on glutathione-agarose beads to 36% purity. Incubated with the fusion protein at a molar ratio of 1:1 at 4 degrees C for 24 h, the solubilized lipase showed lipase activity of about a tenth that of the purified lipase prepared from Pseudomonas aeruginosa TE3285. Magnesium ions and ATP were not essential but increased the activation. When the fusion protein was treated with thrombin to release the glutathione transferase part, it retained its activity. The lipase activation with lipB protein probably proceeds to form a 1:1 complex with the inactive, solubilized lipase protein but by a different mode from known chaperones. PMID- 8344293 TI - Overproduction of S-adenosylmethionine decarboxylase in ethylglyoxal bis(guanylhydrazone)-resistant mouse FM3A cells. AB - A variant cell line, termed SAM-1, which overproduced S-adenosylmethionine decarboxylase (AdoMetDC), was isolated by treatment of mouse FM3A cells with N methyl-N'-nitro-N-nitrosoguanidine and subsequent incubation with ethylglyoxal bis(guanylhydrazone), an inhibitor of the enzyme. The cells were resistant to ethylglyoxal bis(guanylhydrazone), and showed AdoMetDC activity approximately five-times higher than control cells. The rate of AdoMetDC synthesis and the amount of AdoMetDC existing in SAM-1 cells were about five-times those in control cells. The amount of AdoMetDC mRNA existing in SAM-1 cells was five-times more than that in control cells. The amount of 5'-([(Z)-4-amino-2-butenyl]methylamino) 5'-deoxyadenosine, an irreversible inhibitor of AdoMetDC, necessary to inhibit cell growth was also five-times more in SAM-1 cells than in control cells. However, the following were the same in both SAM-1 and control cells; the amount of genomic DNA for AdoMetDC, the size and nucleotide sequence of 5' untranslated region of AdoMetDC mRNA, the deduced amino acid sequence (334 residues) from the nucleotide sequence of AdoMetDC cDNA and the degradation rate (t1/2 = about 4 h) of AdoMetDC. In addition, AdoMetDC mRNA in control cells was slightly more stable than that in SAM-1 cells. The results indicate that the overproduction of AdoMetDC in SAM-1 cells was caused by the increase of AdoMetDC mRNA. The variant cell line is convenient for studying the regulation of AdoMetDC and the physiological function of polyamines. PMID- 8344294 TI - 1H-NMR analysis of turkey egg-white lysozyme and comparison with hen egg-white lysozyme. AB - The complete main chain and approximately 75% of the side chain 1H-NMR assignments of the 129-residue protein, turkey egg-white lysozyme, are presented. NOE data, hydrogen-exchange rates, chemical shifts and coupling constants are reported and are indicative of a structure in solution that is essentially identical to that of the homologous hen egg-white lysozyme. The NH-alpha CH coupling constants of turkey lysozyme are compared to torsion-angle data from three crystal structures of the protein and the results are interpreted in terms of crystal-structure resolution and refinement. PMID- 8344295 TI - Dimeric forms of cholinesterase in Sipunculus nudus. AB - In developing a research on the cholinesterase (ChE) evolution in Invertebrata, this enzyme was studied in the unsegmented marine worm Sipunculus nudus. ChE activity was solubilized through three successive steps of extraction. These fractions are noted as low-salt (LSS), detergent (DS) and high-salt soluble (HSS) and represent 27%, 68% and 5% of total activity, respectively. LSS and DS ChE were purified to homogeneity by affinity chromatography on edrophonium-Sepharose gel. Purification factors of 1700 (LSS) and 1090 (DS) were obtained. The small amount of HSS ChE prevented a similar purification and an extensive characterization. Based on SDS/PAGE and density-gradient centrifugation, both LSS and DS enzymes show a M(r) value of about 130,000 and are likely G2 globular dimers of a 67,000 subunit. Moreover, LSS ChE seems to be an amphiphilic form including a hydrophobic domain, while DS ChE is probably linked to the cell membrane by a phosphatidylinositol anchor. Both LSS and DS enzymes hydrolyze at the highest rate propionylthiocholine. However, they also show a fairly high catalytic efficiency with other thiocholine esters as substrates, thus suggesting a wide and little-specialized conformation of the active site. Based on immunological cross-reactivity trials, LSS and DS ChE from S. nudus show a reduced structural affinity with a molluscan (Murex brandaris) enzyme. HSS ChE, an acetylcholinesterase, is also solubilized by heparin, like typical vertebrate HSS asymmetric enzymes. However, it lacks fast-sedimenting forms and an enzyme anchoring collagenous structure. PMID- 8344296 TI - Analysis of the resistance to heat and hydrogen peroxide stresses in COS cells transiently expressing wild type or deletion mutants of the Drosophila 27-kDa heat-shock protein. AB - The Drosophila melanogaster small heat-shock protein, hsp27 (Dhsp27) belongs to a family of polypeptides which shares a sequence related to alpha-crystallin and which protect cell against heat shock. Dhsp27 accumulates following heat shock and, in absence of stress, in the central nervous system, imaginal discs and the gonads of the developing fly. Two internal and adjacent deletion mutants in the conserved alpha-crystallin domain of Dhsp27 were constructed. Expression vectors containing either the coding sequence of Dhsp27 or that of the two deletion mutants linked to the Simian-Virus-40 late promoter were used to transfect monkey COS cells. The transient expression of Dhsp27 was found to decrease the sensitivity of COS cells to heat and hydrogen-peroxide stresses as judged by Trypan-blue staining and indirect immunofluorescence analysis. Using this rapid test, we observed that a deletion of 62 amino acids, which lies at the 5' end of the conserved alpha-crystallin domain and covers the first 41 amino acids of this region had only a weak effect on the protective activity of Dhsp27. This suggests that the N-terminal half of the conserved alpha-crystallin domain may not be essential for the protective activity of the small hsp. In contrast, Dhsp27 was no more active when the last 42 amino acids of the alpha-crystallin domain were deleted. Biochemical fractionation and indirect immunofluorescence analysis indicated that the protective function of Dhsp27 was localized at the level of the nucleus. PMID- 8344297 TI - Ribosomes terminated in vitro are in a tight association with non-phosphorylated elongation factor 2 (eEF-2) and GDP. AB - A proportion of the ribosome population in the eukaryotic cell is present in the form of single 80-S ribosomes. These are not involved in translation and are tightly associated with eukaryotic elongation factor 2 (eEF-2). The factor dissociates from ribosomes when it is ADP-ribosylated. Attempts at reconstitution of such complexes from ribosomal subunits and eEF-2 were not successful. We have shown that monomeric ribosomes in a tight complex with eEF-2 can be obtained in vitro as terminated ribosomes in a reconstituted translation system containing isolated polyribosomes, elongation factors and pH5 enzymes (all from rabbit reticulocytes). Incubation of the system with radioactive GTP demonstrated that terminated ribosomes contain GDP. ADP-ribosylation of eEF-2 bound to terminated ribosomes by diphtheria toxin leads to dissociation of both eEF-2 and GDP to the same extent. Thus the presence of GDP in terminated ribosomes is eEF-2 dependent. Ribosomes terminated in vitro as well as native single ribosomes contain the non phosphorylated form of eEF-2. We assume that tight association of terminated ribosomes with the non-phosphorylated form of eEF-2 excludes both the ribosome and active eEF-2 from the translational cycle and thus, maintains the optimal proportion of translating ribosomes and free eEF-2 in the cell. PMID- 8344298 TI - Studies on the induction and phosphorylation of xanthine dehydrogenase in cultured chick embryo hepatocytes. AB - Chick embryo hepatocytes, cultured in a chemically defined medium, were used to investigate hormonal requirements for xanthine-dehydrogenase induction and to determine whether the enzyme is phosphorylated. Triiodothyronine is found to be required to induce the synthesis of active enzyme. Inclusion of sodium tungstate in the medium resulted in the complete loss of enzyme activity but no decrease of immunochemically detectable levels of enzyme. Immunoprecipitated xanthine dehydrogenase from cell extracts migrates with enzyme purified from adult chicken liver on SDS/PAGE. Both the native 150-kDa subunit and the 130-kDa form of the enzyme is observed. N-terminal sequence analysis of the 150-kDa subunit shows the following; Ala-Pro-Pro-Glu-Thr-Gly-Asp-Glu-Leu-Val-Phe-Phe-Val-Asn-Gly-Lys-Lys Val- Val which is similar to the published N-terminal sequences of rat, mouse and insect xanthine dehydrogenases. Autoradiography of denaturing gels of xanthine dehydrogenase isolated from 32P(i)-labeled hepatocytes demonstrates that the 150 kDa and the 130-kDa forms of the enzyme are phosphorylated. Chemical phosphate analysis of acid-precipitated, electrophoretically pure chicken liver xanthine dehydrogenase also shows the presence of covalently bound phosphate. Phosphoamino acid analysis of both 32P-labeled forms of the enzyme demonstrates the presence of phosphoserine. Thus, chicken liver xanthine dehydrogenase contains a phosphoserine residue as found previously in bovine milk xanthine oxidase [Davis, M. D., Edmondson, D. E. & Muller, F. (1984) Eur. J. Biochem. 145, 237-250]. PMID- 8344299 TI - Stabilized NMR structure of human parathyroid hormone(1-34). AB - The structure of the biologically-active N-terminal region of human parathyroid hormone, PTH(1-34), was investigated in the presence of 10% trifluoroethanol using two-dimensional proton NMR spectroscopy, distance geometry and dynamic simulated annealing. Complete assignments of all backbone and side chain hydrogens were made with the aid of totally correlated spectroscopy (TOCSY) experiments, providing through-bond 1H-1H connectivities, and NOESY providing through-space and sequential backbone connectivities. Distance and angle constraints were used in the distance geometry algorithm DIANA II to generate a family of structures satisfying all inputs. The lowest energy structures were further refined using the dynamic-simulated-annealing protocol XPLOR 3. The major structural features evident in 10% trifluoroethanol are two segments of alpha helix extending from residues Glu4 to Lys14/His14 and Ser17 to Asp30. A short length of unordered structure joined the two spans of helix. The structures of the N-terminal regions (4-13/14) agreed closely with the structure found in human parathyroid-hormone-related protein (PTHrP)(1-34) obtained earlier by Ray, Barden and Kemp [19]. However, PTHrP(16-19) exhibited a reverse turn which is incorporated in an extended helix in PTH. The consequent interactions between several hydrophobic residues in the C-terminal region in PTHrP are absent in PTH. Moreover, the turn in PTHrP(22-25) at the start of the C-terminal helix is present as a more standard loop of helix in PTH. Comparisons between the structures of the two hormones has enabled the probable location and structure of the PTH receptor-binding site to be placed in the segment of amphiphilic alpha helix (24-31). PMID- 8344300 TI - The isopenicillin-N acyltransferase of Penicillium chrysogenum has isopenicillin N amidohydrolase, 6-aminopenicillanic acid acyltransferase and penicillin amidase activities, all of which are encoded by the single penDE gene. AB - The isopenicillin-N acyltransferase of Penicillium chrysogenum catalyzes the conversion of the biosynthetic intermediate isopenicillin N to the hydrophobic penicillins. The isopenicillin-N acyltransferase copurified with the acyl-CoA:6 aminopenicillanic acid (6-APA) acyltransferase activity which transfers an acyl residue from acyl-CoA derivatives (e.g. phenylacetyl-CoA, phenoxyacetyl-CoA) to 6 APA. Other thioesters of phenylacetic acid were also used as substrates. An amino acid sequence similar to that of the active site of thioesterases was found in the isopenicillin-N acyltransferase, suggesting that this site is involved in the transfer of phenylacetyl residues from phenylacetyl thioesters. Purified isopenicillin-N acyltransferase also showed isopenicillin-N amidohydrolase, penicillin transacylase and penicillin amidase activities. The isopenicillin-N amidohydrolase (releasing 6-APA) showed a much lower specific activity than the isopenicillin-N acyltransferase of the same enzyme preparation, suggesting that in the isopenicillin-N acyltransferase reaction the 6-APA is not released and is directly converted into benzylpenicillin. Penicillin transacylase exchanged side chains between two hydrophobic penicillin molecules; or between one penicillin molecule and 6-APA. The penicillin amidase activity is probably the reverse of the biosynthetic acyl-CoA:6-APA acyltransferase. Four P. chrysogenum mutants deficient in acyl-CoA:6-APA acyltransferase lacked the other four related activities. Transformation of these mutants with the penDE gene restored all five enzyme activities. PMID- 8344302 TI - Extensive accumulation of an extracellular L-amino-acid oxidase during gametogenesis of Chlamydomonas reinhardtii. AB - In a previous study [Bulte, L. & Wollman, F.-A. (1992) Eur. J. Biochem. 204, 327 336], we identified a novel gamete-specific polypeptide of Chlamydomonas reinhardtii, M alpha. This 66-kDa polypeptide reacts with antibodies to cytochrome f and accumulates in gametes only in conditions that promote destabilisation of the cytochrome b6/f complex. Here, we show that M alpha is not a modification product of cytochrome f, but is part of protein M, a high molecular-mass L-amino-acid oxidase located in the periplasm. It catalyzes oxidation of all L-amino acids tested, except cysteine. Using phenylalanine as a substrate, saturation of the enzymatic rate is reached at 2 microM. These characteristics suggest that protein M may operate in vivo as an efficient scavanger of ammonium from extracellular amino acids. The enzyme contains non covalently bound FAD. It exists in two forms with essentially similar enzymatic properties, of 1.2-1.3 MDa and 0.9-1.0 MDa, respectively. The lighter form is an oligomer of M alpha, while the heavier form contains, in addition to M alpha, a second polypeptide of 135 kDa, M beta, in a molar ratio of 3-4 M alpha/M beta. Both polypeptides are glycosylated. PMID- 8344301 TI - L-serine and L-threonine dehydratase from Clostridium propionicum. Two enzymes with different prosthetic groups. AB - L-Serine dehydratase from the Gram-positive bacterium Peptostreptococcus asaccharolyticus is novel in the group of enzymes deaminating 2-hydroxyamino acids in that it is an iron-sulfur protein and lacks pyridoxal phosphate [Grabowski, R. and Buckel, W. (1991) Eur. J. Biochem. 199, 89-94]. It was proposed that this type of L-serine dehydratase is widespread among bacteria but has escaped intensive characterization due to its oxygen lability. Here, we present evidence that another Gram-positive bacterium, Clostridium propionicum, contains both an iron-sulfur-dependent L-serine dehydratase and a pyridoxal phosphate-dependent L-threonine dehydratase. These findings support the notion that two independent mechanisms exist for the deamination of 2-hydroxyamino acids. L-Threonine dehydratase was purified 400-fold to apparent homogeneity and revealed as being a tetramer of identical subunits (m = 39 kDa). The purified enzyme exhibited a specific activity of 5 mu kat/mg protein and a Km for L threonine of 7.7 mM. L-Serine (Km = 380 mM) was also deaminated, the V/Km ratio, however, being 118-fold lower than the one for L-threonine. L-Threonine dehydratase was inactivated by borohydride, hydroxylamine and phenylhydrazine, all known inactivators of pyridoxal-phosphate-containing enzymes. Incubation with NaB3H4 specifically labelled the enzyme. Activity of the phenylhydrazine inactivated enzyme could be restored by pyridoxal phosphate. L-Serine dehydratase was also purified 400-fold, but its extreme instability did not permit purification to homogeneity. The enzyme was specific for L-serine (Km = 5 mM) and was inhibited by L-cysteine (Ki = 0.5 mM) and D-serine (Ki = 8 mM). Activity was insensitive towards borohydride, hydroxylamine and phenylhydrazine but was rapidly lost upon exposure to air. Fe2+ specifically reactivated the enzyme. L Serine dehydratase was composed of two different subunits (alpha, m = 30 kDa; beta, m = 26 kDa), their apparent molecular masses being similar to the ones of the two subunits of the iron-sulfur-dependent enzyme from P. asaccharolyticus. Moreover, the N-terminal sequences of the small subunits from these two organisms were found to be 47% identical. In addition, 38% identity with the N-terminus of one of the two L-serine dehydratases of Escherichia coli was detected. PMID- 8344303 TI - Primary structure of human milk octa-, dodeca- and tridecasaccharides determined by a combination of 1H-NMR spectroscopy and fast-atom-bombardment mass spectrometry. Evidence for a new core structure, the para-lacto-N-octaose. AB - Two octasaccharides, two dodecasaccharides and a tridecasaccharide have been isolated from human milk by a combination of paper chromatography, high performance liquid chromatography and high-performance anion-exchange chromatography. Their structural analysis investigated by 400-MHz 1H- and 13C-NMR spectroscopy and by mass spectrometry led to the following structures. [formula: see text] The two octasaccharides have been previously characterized in human milk; the complete assignment of the 1H and 13C spectra is reported here. One of the dodecasaccharides is a tetrafucosyl derivative with a new core: typeI-(beta 1 3)-typeII-(beta 1-3)-typeII-(beta 1-3)-Gal((beta 1-4)Glc, where typeI = Gal(beta 1-3)GlcNAc and typeII = Gal(beta 1-4)GlcNAc. These oligosaccharides display simultaneously Lewis(b) and Lewis(x) determinants or Lewis(a), Lewis(b) and Lewis(x) determinants. PMID- 8344304 TI - Kinetics of cytochromes P-450 IA1 and IIB1 in reconstituted systems with dilauroyl- and distearoyl-glycerophosphocholine. AB - In the present study the effect of changing the fatty acyl moiety of phosphatidylcholine from dilauroyl to distearoyl on the kinetic parameters of O dealkylation of alkoxyresorufins and ethoxycoumarin dependent on reconstituted cytochromes P-450 IA1 and IIB1 has been investigated. The results demonstrate that (a) the maximum rate of O-dealkylation (V) for both P-450 enzymes was about two times higher in the L-alpha-dilauroyl-sn-glycero-3-phosphocholine (Lau2GroPCho) system and (b) changes in the fatty acyl moiety of phosphatidylcholine (acyl2GroPCho) from dilauroyl to distearoyl affected the apparent Km for the substrate (Kms) of P-450 IA1 and IIB1 in a different way. In addition, (c) the kinetic parameters appeared to be dependent on the acyl2GroPCho/P-450 ratio and a change in this ratio affected the kinetic parameters of P-450 IA1 and IIB1 in a different manner. From these last two observations it was concluded that the mechanism by which phospholipids influence P-450-IIB1-dependent O-dealkylation of ethoxycoumarin is different from that by which they influence P-450-IIB1-dependent O-dealkylation of this substrate. Furthermore, the results of the present study demonstrate that the increase in the rate of O-dealkylation of ethoxycoumarin, reported in the literature for reconstituted systems in the presence of Lau2GroPCho, results from an effect of Lau2GroPCho on both the Kms and the V. In a number of additional experiments possible mechanisms underlying the observed differential effect of Lau2GroPCho and Ste2GroPCho on the Kms and V of P-450 IA1 and IIB1 were investigated. This was done by studying the effect of the two acyl2GroPCho species on the kinetic parameters of some of the different steps of the P-450 cycle, namely substrate binding, oxygen binding and the rate of electron transfer. The results demonstrate an influence of Lau2GroPCho and Ste2GroPCho on (a) substrate binding to cytochrome P-450, (b) the affinity of cytochromes P-450 for NADPH-cytochrome reductase and thus on (c) the electron flow through the reconstituted system. Based on the results from these experiments it was concluded that the increased V of P-450 IA1 and IIB1 in the presence of Lau2GroPCho compared to the systems with Ste2GroPCho was at least in part due to an increased affinity of both P-450 enzymes for NADPH-cytochrome reductase in the presence of Lau2GroPCho compared to Ste2GroPCho.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8344305 TI - Rat brain cytosol contains a factor which reconstitutes guanine-nucleotide binding-protein-regulated phospholipase-D activation in HL60 cells previously permeabilized with streptolysin O. AB - We report that guanosine 5'-[gamma-thio]triphosphate (GTP[S]) can stimulate phospholipase D (PLD) in HL60 cells acutely permeabilized with streptolysin O. The ability of GTP[S] to stimulate PLD is impaired if the cells are previously permeabilized such that the majority of the cytosol has leaked out. Rat brain and HL60 cytosols were both found to restore GTP[S]-stimulated PLD activity in a reconstitution assay consisting of previously permeabilized HL60 cells. Rat brain cytosol was fractionated on heparin agarose and assayed for reconstitution of GTP[S]-stimulated PLD activity. The active fractions were pooled, concentrated and chromatographed on gel filtration to assess its molecular mass. The molecular mass of the reconstituting factor was found to be 16 kDa. Reconstitution by the cytosolic factor was dependent on GTP[S]. Ca2+ (pCa 5), MgATP and MgCl2 enhanced GTP[S]-dependent reconstitution of PLD activity in the previously permeabilized HL60 cells. These results demonstrate the presence in rat brain cytosol of a factor which is an activator of GTP[S]-stimulated PLD. PMID- 8344306 TI - cDNA cloning of the sodium-influx-stimulating peptide in the mollusc, Lymnaea stagnalis. AB - We isolated and characterized a cDNA clone, encoding the prohormone of the sodium influx-stimulating (SIS) peptide of the freshwater snail Lymnaea stagnalis. The prohormone is cleaved to generate a signal peptide of 23 amino acids and a SIS peptide of 77 amino acids. The SIS peptide as encoded by the cDNA represents a novel and complex neuropeptide, which controls the activity of sodium pumps in the integument, pericardium, ureter and nephridial gland. In situ hybridization showed that the SIS-peptide gene is expressed by the neuroendocrine, so-called Yellow Cells of the central nervous system. PMID- 8344307 TI - Calcium binding by chick calretinin and rat calbindin D28k synthesised in bacteria. AB - Calretinin is a member of the EF-hand calcium-binding protein family, with a high similarity with calbindin D28k. The chick calretinin cDNA sequence was reconstructed in a M13 vector and transferred into an expression plasmid derived from the pET series. The calretinin gene was expressed in Escherichia coli and produced immunoreactive calretinin of the expected size. Bacterially expressed calretinin was purified with successive ammonium-sulfate precipitation, DEAE chromatography, hydroxyapatite chromatography, Sephadex G-75 chromatography and Mono-Q chromatography. Normally, 1.0-1.5 mg calretinin was obtained from 1 l bacterial culture with a protein recovery of 0.5-1.5%. Calbindin D28k was purified similarly from bacteria using an expression plasmid provided by W. Hunziker. Calcium-binding activity of purified proteins was measured by equilibrium dialysis in calcium/EGTA mixtures with 45Ca as tracer. Both calretinin and calbindin D28k bound 3-4 Ca2+/molecule (calretinin, 4.0 +/- 0.5; calbindin D28k, 3.5 +/- 0.4), implying that at least one of the canonical EF-hand domains does not bind calcium. The Kd was 0.3-0.5 microM with little difference between the values for the two proteins. PMID- 8344308 TI - The variants of the protein toxins abrin and ricin. A useful guide to understanding the processing events in the toxin transport. AB - Kinetic data on inhibition of protein synthesis in thymocyte by three abrins and ricin have been obtained. The intrinsic efficiencies of A chains of four toxins to inactivate ribosomes, as analyzed by ki-versus-concentration plots were abrin II, III > ricin > abrin I. The lag times were 90, 66, 75 and 105 min at a 0.0744 nM concentration of each of abrin I, II, III and ricin, respectively. To account for the observed differences in the dose-dependent lag time, functional and structural variables of toxins such as binding efficiency of B chains to receptors and low-pH-induced structural alterations have been analyzed. The association constants obtained by stopped flow studies showed that abrin-I (4.13 x 10(5) M-1 s-1) association with putative receptor (4-methylumbelliferyl-alpha-D galactoside) is nearly two times more often than abrin III (2.6 x 10(5) M-1 s-1) at 20 degrees C. Equilibrium binding constants of abrin I and II to thymocyte at 37 degrees C were 2.26 x 10(7) M-1 and 2.8 x 107 M-1 respectively. pH-induced structural alterations as studied by a parallel enhancement in 8-anilino-L naphthalene sulfonate fluorescence revealed a high degree of qualitative similarity. These results taken with a nearly identical concentration-independent lag time (minimum lag of 41-42 min) indicated that the binding efficiencies and internalization efficiencies of these toxins are the same and that the observed difference in the dose-dependent lag time is causally related to the proposed processing event. The rates of reduction of inter-subunit disulfide bond, an obligatory step in the intoxication process, have been measured and compared under a variety of conditions. Intersubunit disulfide reduction of abrin I is fourfold faster than that of abrin II at pH 7.2. The rate of disulfide reduction in abrin I could be decreased 11-fold by adding lactose, compared to that without lactose. The observed differences in the efficiencies of A chains, the dose dependent lag period, the modulating effect of lactose on the rates of disulfide reduction and similarity in binding properties make the variants a valuable tool to probe the processing events in toxin transport in detail. PMID- 8344309 TI - Purification and properties of an iron-sulfur and FAD-containing 4-hydroxybutyryl CoA dehydratase/vinylacetyl-CoA delta 3-delta 2-isomerase from Clostridium aminobutyricum. AB - 4-Hydroxybutyryl-CoA dehydratase, the key enzyme in the metabolism of gamma aminobutyrate in Clostridium aminobutyricum, represents approximately 15-25% of the soluble protein. The enzyme was purified to homogeneity under anaerobic conditions to a specific activity of 209 nkat mg-1. The dehydratase catalyses the reversible conversion of 4-hydroxybutyryl-CoA (Km = 50 microM) to crotonyl-CoA and possesses a probably intrinsic vinylacetyl-CoA delta 3-delta 2-isomerase with a specific activity of 223 nkat mg-1. The equilibrium of the reversible dehydration was determined from both sides as K = [crotonyl-CoA]/[4 hydroxybutyryl-CoA] = 4.2 +/- 0.3. Cyclopropylcarboxyl-CoA was not converted to crotonyl-CoA. The native enzyme has an apparent molecular mass of 232 kDa and is composed of four apparently identical subunits (molecular mass = 56 kDa), indicating a homotetrameric structure. Under anaerobic conditions the active enzyme revealed a brown colour and contained 2 +/- 0.2 mol FAD (64 +/- 5% oxidized), 16 +/- 0.8 mol Fe and 14.4 +/- 1.2 mol inorganic sulfur, which probably form iron-sulfur clusters. Exposure to air resulted initially in a slight activation followed by irreversible inactivation. Concomitantly the vinylacetyl-CoA delta-isomerase activity was lost and the colour of the enzyme changed to yellow. Reduction by sodium dithionite yielded inactive enzyme which could be completely reactivated by oxidation with potassium hexacyanoferrate(III). The data indicate that the active enzyme contains oxidized FAD despite its sensitivity towards oxygen. During the dehydration a non activated C-H bond at C-3 of 4-hydroxybutyryl-CoA has to be cleaved. A putative mechanism for 4-hydroxybutyryl-CoA dehydratase is proposed in which this cleavage is achieved by a FAD-dependent oxidation of 4-hydroxybutyryl-CoA to 4 hydroxycrotonyl-CoA. In a second step the hydroxyl group is substituted by a hydride derived from the now reduced FAD in an SN2' reaction leading to vinylacetyl-CoA. Finally isomerisation yields crotonyl-CoA. 4-Hydroxybutyryl-CoA dehydratase is quite distinct from 3-hydroxyacyl-CoA dehydratase (crotonase) and 2-hydroxyacyl-CoA dehydratases. Contrary to the latter enzyme [e.g. (R)-lactyl CoA dehydratase and (R)-2-hydroxyglutaryl-CoA dehydratase] which are composed of three different subunits and similarly catalyse the cleavage of a non activated C H bond at C-3, 4-hydroxybutyryl-CoA dehydratase does not require ATP, MgCl2 and Ti(III)citrate for activity. Furthermore 4-hydroxybutyryl-CoA dehydratase is not inactivated by oxidants such as 5 mM 4-nitrophenol, 5 mM chloramphenicol and 5 mM hydroxylamine. PMID- 8344310 TI - 1H-NMR study of reduced heme proteins myoglobin and cytochrome P450. AB - The 1H-NMR spectra of deoxymyoglobin and reduced cytochrome P450 are analyzed by NOE spectroscopy. Progress has been made in the assignment of the hyperfine shifted signals of deoxymyoglobin. The nuclear longitudinal-relaxation-time values indicate short electron-relaxation times whereas Curie relaxation contributes significantly to the signals linewidths. For reduced cytochrome P450 the linewidths are larger due to the Curie-relaxation contribution in a large protein. Therefore, the spectral information is poor. The electron-relaxation rates are discussed in terms of possible electronic structure. PMID- 8344311 TI - Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily. AB - A cDNA that codes for two peptides in the glucagon superfamily has been isolated from sockeye salmon brain. The first peptide is related to growth hormone releasing hormone (GHRH), which has high sequence similarity with PACAP-related peptide. The second peptide is structurally related to vasoactive intestinal peptide, which is also related to a newly identified peptide in mannals, pituitary adenylate-cyclase-activating polypeptide (PACAP). The salmon precursor contains 173 amino acids and has dibasic and monobasic enzyme-processing sites for cleavage of a 45-amino-acid GHRH-like peptide with a free C-terminus and a 38 amino-acid PACAP with an amidated C-terminus. The salmon GHRH-like peptide has 40% amino acid sequence identity with a human GHRH and 56% identity with human PACAP-related peptide. The 38-amino-acid salmon PACAP is highly conserved (89-92% identity) with only three or four amino acid substitutions compared with the human, ovine and rat 38-amino-acid PACAP. Not previously reported for mammalian species, a short precursor coding for only one peptide exists in salmon in addition to the long precursor coding for two peptides. In the short precursor, the coding region for GHRH is deleted leaving the PACAP-coding region in a correct reading frame. This provides one possible control mechanism for an increased expression of one peptide (PACAP) without the concomitant increase in the other peptide (GHRH) as occurs in a double-peptide precursor. The importance of the 3' non-translated region of the salmon GHRH/PACAP precursor in the regulation of translation is suggested by its 70% nucleotide sequence identity to the 3' non-translated regions of the mammalian PACAP precursors. The structural organization of the salmon GHRH/PACAP precursor provides a possible evolutionary scheme for precursors that contain tandem peptides in the glucagon superfamily. PMID- 8344312 TI - Cell swelling and the sensitivity of autophagic proteolysis to inhibition by amino acids in isolated rat hepatocytes. AB - In the isolated perfused rat liver, autophagic proteolysis is inhibited by hypo osmotic perfusion media [Haussinger, D., Hallbrucker, C., vom Dahl, S., Lang, F. & Gerok, W. (1990) Biochem. J. 272, 239-242]. Here we report that in isolated hepatocytes, incubated in the absence of amino acids to ensure maximal proteolytic flux, proteolysis was not inhibited by hypo-osmolarity while the synthesis of glycogen from glucose, a process known to be very sensitive to changes in cell volume [Baquet, A., Hue, L., Meijer, A. J., van Woerkom, G. M. & Plomp, P. J. A. M. (1990) J. Biol. Chem. 265, 955-959], was stimulated under identical conditions. However, in isolated hepatocytes, hypo-osmolarity increased the sensitivity of autophagic proteolysis to inhibition by low concentrations of amino acids. The anti-proteolytic effect of hypo-osmolarity in our experiments was not due to stimulation of amino-acid transport into the hepatocytes: neither the consumption of most amino acids, nor the rate of urea synthesis was appreciably affected by hypo-osmotic incubation conditions. In the course of these studies we also found that hypo-osmolarity increased the affinity of protein synthesis for amino acids. In the presence of amino acids the intracellular level of ATP was not much affected. However, because of cell swelling under these conditions the intracellular concentration of ATP decreased. It is proposed that a small part of the inhibition of proteolysis by amino acids may be due to this fall in ATP concentration. PMID- 8344313 TI - Distinct mechanisms of phospholipase D activation and attenuation utilized by different mitogens in NIH-3T3 fibroblasts. AB - The activation of phospholipase D (PLD) by platelet-derived growth factor (PDGF), prostaglandin F2 alpha and 12-O-tetradecanoylphorbol 13-acetate (TPA) was studied in NIH-3T3 fibroblasts. PLD activation was determined by measuring the production of both [3H]phosphatidic acid and [3H]phosphatidylpropanol (products of the PLD catalyzed hydrolysis and transphosphatidylation reactions, respectively), in cells that were metabolically pre-labeled with [3H]oleic acid. All mitogens caused a rapid (within 2 min) activation of PLD. Activation of PLD by prostaglandin F2 alpha and PDGF was transient and declined to near basal levels by 15 min and 55 min, respectively. In contrast, TPA-induced activation of PLD was sustained for at least 60 min of incubation. A combination of maximally effective concentrations of PDGF and TPA stimulated PLD activity in a non additive manner, while the effect of prostaglandin F2 alpha was additional to that of either PDGF or TPA. The protein kinase inhibitor staurosporine inhibited PLD activation by PDGF or TPA with almost identical dose/response curves. In contrast, staurosporine potentiated prostaglandin-F2 alpha-induced PLD activation. The specific protein kinase C inhibitor GF109203X (a bisindolylmaleimide) inhibited PLD activation by prostaglandin F2 alpha and PDGF at concentrations higher than those required for inhibition of PLD activation induced by TPA. Depletion of cellular protein kinase C abolished PLD activation by all three mitogens without affecting in vitro activity of membrane-bound PLD. The distinct kinetics of PLD activation and its differential susceptibility to protein kinase inhibitors suggest the existence of agonist-specific activation and/or inactivation mechanisms. The results indicate also that protein kinase C participates in the mechanism of PLD activation via PDGF, while the effect of prostaglandin F2 alpha involves a pathway independent of protein kinase C. PMID- 8344314 TI - The bis(adenosin-N6-yl) alkanes, a family of potential dinucleoside polyphosphate analogue precursors. Mechanism of growth inhibition and suppression of adenosine toxicity in lymphoid cells. AB - The potential diadenosine polyphosphate analogue precursor, bis(adenosin-N6 yl)dodecane (A[CH2]12A) (Chen, H. & McLennan, A. G. (1993) Eur. J. Biochem. 213, 935-944.) is equally toxic to both wild-type and adenosine-kinase-deficient BHK cells at concentrations up to 100 microM; at higher concentrations, wild-type cells are more sensitive, as are cells over-expressing adenosine kinase. Thus both the nucleoside and its nucleotide products are toxic. In contrast to adenosine toxicity, the toxicity of A[CH2]12A to S-49 T-lymphoma cells could not be reversed by uridine or by L-homocysteine thiolactone. A[CH2]12A and all its shorter chain bis(adenosin-N6-yl)alkane homologues could relieve the toxicity of low adenosine concentrations (< 20 microM) to S-49 cells, mainly through inhibition of adenosine kinase, while relief of the toxicity of high adenosine concentrations (> 20 microM) required the longer chain homologues. A[CH2]12A at 10 microM completely eliminated adenosine toxicity. Deoxyadenosine toxicity could also be relieved, but only that due to low concentrations (< 4 microM). A[CH2]12A had only a slight stimulatory effect on S-adenosylhomocysteine-hydrolase activity. PMID- 8344315 TI - Refolding and single-step purification of porcine interferon-gamma from Escherichia coli inclusion bodies. Conditions for reconstitution of dimeric IFN gamma. AB - Recombinant porcine interferon-gamma, overexpressed in Escherichia coli, was found to accumulate in cytoplasmic inclusion bodies. The influence of various physicochemical parameters on refolding was investigated using 6 M guanidine/HCl solubilised inclusion bodies which had been purified by ultracentrifugation on a sucrose step gradient. It appeared that the yield of reconstitution of denatured protein reached 60-70% under optimum conditions, i.e. at an intermediary guanidine/HCl concentration of 0.5 M and at a protein concentration of 10-20 microM (0 degrees C). Since intermediary guanidine/HCl concentrations at 0.5-1.65 M increasingly promoted off-pathway formation of soluble aggregates and at 0.5 0.2 M progressively promoted precipitation, maximal recovery of biologically active protein required a twofold transition in the surrounding guanidine/HCl concentration (6 M-->0.5 M-->0 M). A single additional size-exclusion chromatographic step yielded a final product that was > 99.5% pure, had specific antiviral activity > 10(7) U/mg protein and contained < or = 25 pg/ml endotoxin. Cross-linking by means of disulfosuccinimidyl tartarate revealed that the refolded protein possessed a dimeric structure. Furthermore, we have characterized three different molecular species of recombinant porcine interferon gamma that are formed under non-optimal refolding conditions (1 M guanidine/HCl) and that differ from each other in specific activity, size and stability. One of these converts irreversibly into dimeric interferon-gamma in a temperature dependent manner and is therefore considered as a productive folding intermediate. PMID- 8344316 TI - Docking the mitochondrial inhibitor protein IF1 to a membrane receptor different from the F1-ATPase beta subunit. AB - Monoclonal antibodies reacting with the inhibitor protein (IF1) of the mitochondrial ATPase/ATP synthase complex did not modify the IF1-induced inhibition of soluble F1 ATPase activity. On the contrary, they increased the ATPase activity of inverted electron-transport particles without inducing a significant release of IF1 from these particles. This suggested that IF1 could be linked to a membrane protein when it was not inhibiting the ATPase activity. IF1 antibodies have been used to show that IF1 can bind not only to the beta subunit of F1-ATPase [Klein, G., Satre, M., Dianoux, A. C. & Vignais, P. V. (1981) Biochemistry 20, 1339-1344] but also to a protein present in the inner mitochondrial membrane. The cross-linking of IF1 to this membrane protein gave a product of M(r) 15000-16000 that migrated differently from IF1 and from the dimer of IF1 using SDS/PAGE. When the cross-linked product was obtained by using a cleavable cross-linking reagent, the complex between IF1 and the docking protein was partly dissociated and free IF1 was recovered. Considering the molecular mass of IF1, this docking protein for IF1 has apparent M(r) 5000-6000. The complex between IF1 and this receptor protein can be detected in low amounts by antibodies against IF1 in the absence of cross-linking reagent. Since this complex remained in the pellet after treatment of the membrane with Triton X-100, it should be a membrane protein. Therefore, IF1 can bind not only to its inhibitory-binding site at the beta subunit of F1, but also to a non inhibitory site which is a membrane protein of approximate M(r) 5000-6000. PMID- 8344317 TI - Distribution of alcohol and sorbitol dehydrogenases. Assessment of mRNA species in mammalian tissues. AB - The tissue distribution of mRNA of alcohol dehydrogenases of classes I, II and III, and sorbitol dehydrogenase, was studied. mRNA from 19 different rat tissues was purified and analyzed by Northern blots, utilizing cDNA probes specific for the four dehydrogenases. Class-I alcohol-dehydrogenase mRNA was shown to be of widespread occurrence, detectable in all tissues including brain, but with pronounced differences in amounts. Hybridization revealed the pattern of occurrence of class-II alcohol-dehydrogenase mRNA to be unique, with transcripts only in the liver, duodenum, kidney, stomach, spleen and testis. Abundant levels of class-III alcohol-dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) mRNA were present in all tissues analyzed, reflecting the general need for scavenging of formaldehyde in physiological cytoprotection. Sorbitol dehydrogenase mRNA was detected in all tissues except small intestine, in agreement with sorbitol resorbtion by passive diffusion in this tissue. In addition, evidence for a sex-specific expression, in the liver, of class-II alcohol dehydrogenase was obtained. PMID- 8344318 TI - Therapy for urologic complications secondary to irradiation of gynecologic malignancies. AB - Hemorrhagic cystitis, ureteral stenosis or obstruction, and bladder fistulas are the most serious urologic complications secondary to pelvic irradiation for gynecologic malignancies. Hemorrhagic cystitis is usually controlled by formalin instillation. In instances of ureteral stenosis or obstruction or bladder fistulas, the possibility of tumor recurrence must be eliminated. Most patients with ureteral stenosis or obstruction will require surgical correction. Most patients with bladder fistulas will be best served by creation of an ileal conduit. In selected patients, closure of the fistula with pedicle flaps will be possible. PMID- 8344319 TI - Cervical metastases in advanced ovarian malignancies. AB - Cervical metastases from ovarian malignancies are a rare event. In order to better define the incidence and pathogenesis of this phenomenon we retrospectively reviewed the charts and pathologic material from 171 Stage III ovarian malignancies. Nine patients (5.3%) were identified with cervical metastases and three patterns of spread to the cervix were recognized: 1) lymphatic permeation only; 2) para-cervical soft tissue extension and 3) direct stromal myometrial invasion. All of the patients with cervical metastases had high grade (Broder's grade III or IV) tumors and extensive abdominal disease at presentation. Although four patients had a positive or suspicious pap smear, none of these had cervical involvement. We conclude that ovarian metastases to the cervix are a rare event, occurring late in the course of the disease and arise from a variety of modes of spread. PMID- 8344320 TI - CA 125 in preoperative evaluation of pelvic masses. AB - Serum CA 125 levels were measured preoperatively in 126 women subjected to laparotomy due to palpable pelvic mass. Forty out of 42 patients with true malignant serous ovarian carcinoma had serum CA 125 levels higher than 35 U/ml. Among 62 patients with some types of gynecologic malignancy, 48 also met the cutoff value of 35 U/ml. Sensitivity, specificity, positive and negative predictive value of CA 125 as a tumor marker, proved to be satisfactory. These results suggest that CA 125 assay can be used as a diagnostic adjunct in the preoperative evaluation of patients with a pelvic mass. PMID- 8344321 TI - Age is prognostic variable in cervical squamous cell carcinoma. AB - A clinico-pathologic review was performed on all younger (under 35 years) and older (55 years or over) women with a diagnosis of cervical squamous cell carcinoma assessed at the Tom Baker Cancer Centre from 1980 to 1985 to determine the effect of age at diagnosis on survival. 45 younger women were identified: 32 were Stage IB; 10, Stage II; and 3, Stage III. 64 older women were identified: 16 were Stage IB; 30, Stage II; 14, Stage III; and 4, Stage IV. For Stage IB women, 40.6% of younger patients developed persistent or recurrent disease and all except one are dead; only one (6.2%) older woman's tumour recurred and she is alive with disease. Younger women had a poorer disease-free survival not only for Stage IB disease (p = 0.014) but also in Stages II and III (p = 0.020). In this study age at diagnosis was an independent prognostic variable with younger women having a poorer disease-free and overall survival. PMID- 8344322 TI - Comprehensive breast diagnosis. AB - Applying a comprehensive diagnostic approach to breast pathology (clinical information, physical exam, state of the art mammography complemented by ultrasonography) 36,396 patients were evaluated. 462 malignancies (40%) were found. 81.2% of carcinomas were clinically occult. 45.2% of the non-palpable lesions were 1 cm or smaller. The yield of carcinomas was 1 every 2.7 biopsies. The preoperative diagnosis of presumptive extensive intraductal component was 85% correct. This information helps to define the excisional limits and upon pathological confirmation select the appropriate surgical therapy: lympectomy vs. mastectomy. PMID- 8344323 TI - Application of short-wave therapy in complex treatment for endometrial cancer. AB - The dynamics of the cellular immunity indices have been studied in 81 patients with endometrial cancer, during the period of combined surgery and post-operative gamma-therapy and also during short-wave therapy. The results obtained testify to the immunostimulating and immunomodulating effect of electromagnetic irradiation of short-wave frequency, thus providing rehabilitation of the immune system in endometrial cancer patients and serving as the basis for short-wave therapy, including it in the complex of therapies given to this group of patients. PMID- 8344324 TI - Simplified ondansetron regimens for antiemetic prophylaxis in cisplatin-based chemotherapy of ovarian cancer. AB - In past years prevention of emesis and nausea induced by antiblastics has been based on extremely heterogeneous protocols with little efficacy. However, by the use of selective antagonists of serotonin S3 receptors there has been a remarkable improvement in the control of side effects. Among these antagonists ondansetron has been till now the most studied. The dosage protocols with which it has usually been employed establish an i.v. administration of the drug of 1 mg/h for 24 hours or the repetition of ondansetron 0.15 mg/kg x 2 every 2-4 hours after the end of chemotherapy. In our study, carried out from September 1991 till September 1992, 21 patients affected by ovarian carcinoma and treated by cisplatin chemotherapy protocols were evaluated (for a total of 63 cycles). Ten patients were under first line adjuvant chemotherapy treatment, whereas 11 patients were in relapse and had already undergone previous antiblastic treatments with serious side effects. In 18 out of 21 patients cyclophosphamide which has a strong emetic factor was associated with cisplatin. According to the total quantity of cisplatin contained in each cycle (in all < or =/> 100 mg) we used ondansetron in two different dosages simplified and shortened in time. They have been illustrated with particular details in the text. The control of nausea and vomiting during the first 24 hours was similar to the controls obtained in other studies in which ondansetron was administered according to the "traditional schemes".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344325 TI - Primary squamous cell carcinoma of the endometrium. Case report. PMID- 8344326 TI - Recurrent endometrial cancer arising in the round ligament. AB - An unusual case of recurrent endometrial carcinoma presenting as a round ligament metastasis is discussed. The primary lesion detected six years earlier was a well differentiated lesion with less than 50% myometrial invasion located in the fundus. A persistent inguinal swelling represented a metastasis to the round ligament. Histologic examination revealed a poorly differentiated adenocarcinoma. Patients with early stage well-differentiated endometrial carcinoma are not immune from late recurrence. PMID- 8344327 TI - Cisplatin-based chemotherapy in recurrent or high risk ovarian granulosa-cell tumor patients. AB - Nine chemotherapy-naive women with recurrent (2 patients) or high risk factors (bilateral or extraovarian spread, poorly-differentiated tumor, age > or = 40 years at diagnosis, residual disease after surgery) granulosa-cell tumors were treated with cisplatin, cyclophosphamide with or without doxorubicin (PAC, PC) or cisplatin, etoposide and bleamycin (PVP-16B). Toxicity was acceptable and the most frequently encountered adverse reactions were WHO grade 3 gastrointestinal toxicity in 77% of patients, and grade 3 myelosuppression in 22% of cases. Clinical complete response was achieved in the 2 patients with recurrent disease. Five patients underwent second look surgery which documented: complete response in 3 patients, partial response in 1 patient and progressive disease in 1 case. Median survival was 85 months (range 14-103). Cisplatin-based cytotoxic regimens may be of benefit in the treatment of recurrent or high risk granulosa-cell tumors. PMID- 8344328 TI - The surgical management of recurrent carcinoma of the vulva. AB - One hundred and two patients with recurrent vulvar cancer were treated with surgical re-excision. At follow-up 57 patients (56%) were free of disease and 45 were dead of disease. The cumulative 2-year and 5-year survivals were 74% and 61%, respectively. Fifty-seven patients had a recurrence within 2 years and 27 were free of disease, 30 patients relapsed between 2-10 years of whom 21 were free of disease, 15 patients relapsed after 10 years and 9 were free of disease. At the time of recurrence progression of metastatic disease to the groin lymph nodes was found in 30 cases, and all of these patients died of disease. Fifty seven of 72 patients remained free of disease when the lymph nodes were not involved (P < .00001). Radical excision of localized recurrent vulvar cancer provides acceptable survival results when the regional lymph nodes are not involved. PMID- 8344329 TI - Prevention of complications of subcutaneous peritoneal access devices in intraperitoneal chemotherapy of ovarian carcinoma. AB - The experience from 133 patients with ovarian cancer treated with intraperitoneal chemotherapy are reported. Type of PAC, the patient suitable for IP chemotherapy, the surgeon and the implantation technique and the timing are discussed with special attention to avoid complications in these patients. PMID- 8344330 TI - Cervical cancer in Khon Khaen University Hospital, Thailand 1985-1990. AB - From 1985 to 1990, 3040 patients with carcinoma of the uterine cervix were diagnosed and treated at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. The epidemiological aspects including ages and geographical distributions, histology, stages, treatment and outcome were presented and compared with those of the previous report. PMID- 8344331 TI - Pathogenesis of genetic haemochromatosis. AB - Genetic haemochromatosis is an autosomal recessive inherited iron overload disease. The genetic defect and the underlying metabolic error are not known. Several observations indicate that the 2-4-fold increase of iron absorption is due to a regulatory defect of a membrane iron transport system in duodenal mucosal cells. The key pathophysiologic factor may be the increase of gut-derived non-transferrin bound iron liganded to low-molecular mass organic molecules. A putative membrane carrier protein for non-transferrin bound iron was identified and preliminary data suggest its enrichment in plasma membranes of human mucosal cells as well as in liver and other organs which are affected in genetic haemochromatosis. Cellular accumulation of ionic iron leads to peroxidative decomposition of organelle membrane phospholipids with the consequence of cell degeneration and cell death. Impairment of organ function and structural alterations such as cirrhosis of the liver are clinical manifestations. PMID- 8344332 TI - The aetiology of clubbing and hypertrophic osteoarthropathy. AB - The evidence is reviewed for the hypothesis that clubbing and hypertrophic osteoarthropathy are due to the peripheral impaction of megakaryocytes and platelet clumps in the fingers and toes, to which this particulate matter has passed in an axial stream. The normal pulmonary vascular bed retains these large particles, which fragment before entering the systemic circulation. A right-to left shunt allows them to bypass the pulmonary vascular bed. A preliminary histological report of platelet clumps seen at necropsy in nail bed capillaries of clubbed fingers supports the hypothesis. Platelets contain and release platelet-derived growth factor, whose known effects could explain all the pathological changes in clubbing. In addition to explaining why clubbing should occur in cyanotic congenital heart disease, clubbing in sub-acute bacterial endocarditis and distal to infected arterial grafts and aneurysms can be understood in terms of platelet clumps breaking off valves or arterial walls, and passing distally. Clubbing in liver disease is associated with multiple small pulmonary arteriovenous anastomoses which allow large particles through. Hypertrophic osteoarthropathy probably shares the same mechanism, and is mainly attributable to PDGF release; but there may also be altered platelet function and an additional growth factor derived from the lungs. PMID- 8344333 TI - Measuring collagen degradation. PMID- 8344334 TI - Factors affecting the assay of urinary 3-hydroxy pyridinium crosslinks of collagen as markers of bone resorption. AB - The measurement of the 3-OH pyridinium compounds, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), in urine by high performance liquid chromatography is potentially useful in clinical studies, since they are specific biochemical markers of bone resorption. The aims of the present study were to improve assay performance and optimize sample collection. An isocratic high performance liquid chromatogram (HPLC) separation with baseline resolution was accomplished within 4 min using heptafluorobutyric acid as an ion-pair. The sample preparation for HPLC, using CF1 cellulose, produced uncontaminated samples with a recovery higher than 90% for both crosslinks. An elastin-derived material, tentatively identified as isodesmosine (Ides), was also tested and proved to be a suitable internal standard. Use of this standard improved assay precision. The effect of an oral gelatin load on the excretion of Pyr and Dyr was investigated. The creatinine corrected excretion of Pyr and Dpyr was unchanged over a 6 h period, in contrast to the 10-fold increase in the excretion of urinary hydroxyproline with a peak 2 4 h after ingestion. In 20 postmenopausal women, 2 h fasting morning urine results correlated with results from 24-h urine collections Dpyr/Cr (r = 0.70, n = 20). There was a day-to-day variation of 26% in adults studied for 10 days. PMID- 8344335 TI - Tritium and 14C isotope effects using tracers of leucine and alpha ketoisocaproate. AB - To test if different leucine tracers behave in an indistinguishable manner and, by implication, that their metabolism is identical to that of natural leucine, we measured whole body leucine turnover in dogs and humans and fibrinogen synthesis in dogs by simultaneously infusing either [1-14C]leucine or [4,5-3H]leucine or [1 14C]alpha-ketoisocaproate (KIC) and [4,5-3H]KIC. Whole body leucine fluxes calculated from the plasma specific activity of the transaminated product of the infused tracer (reciprocal pool model) were lower (dogs by 5.7%; humans by 6.4%, both P < 0.02) when the plasma 3H specific activity compared to 14C specific activity were used with leucine tracers and were also lower (dogs by 4.4%, P < 0.02; humans by 8.6%, P < 0.06) using the KIC tracers. Using leucine or KIC tracers in dogs, the fractional rate of fibrinogen synthesis was 6.7% or 9.4% lower, respectively, (P < 0.02) using the 3H versus the 14C tracer. The apparently lower incorporation of 3H into protein was only in part accounted for by detritiation (2.1%, P = 0.05) of [3H]leucine during acid hydrolysis of proteins. These results suggest that in vivo and/or in vitro differential isotope effects are small (approximately 5%), but should be considered when dual isotopes infusions are employed to partition amino acid metabolism. PMID- 8344336 TI - Influence of platelet size before coronary angioplasty on subsequent restenosis. AB - Platelet size has been shown to reflect platelet activity. We prospectively measured the mean platelet volume (MPV) in 47 patients undergoing single vessel angioplasty for symptomatic angina. The patients underwent repeat angiography 4-8 months later irrespective of symptomatic status. Restenosis was assessed quantitatively by hand held calliper measurements of the lesion and qualitatively by a return of angina, ST segment changes on an exercise test and visual analysis of the lesion severity by two experienced angiographers. Twenty-four patients developed recurrent angina during the follow-up period, the MPV in the group with chest pain was 8.54 +/- 0.60 fl compared to 8.1 +/- 0.69 fl in the asymptomatic group (P = 0.04). Twenty two patients had significant ST segment changes at exercise. In this group the MPV was 8.6 +/- 0.56 fl compared to 8.0 +/- 0.70 fl for the group with a negative test (P = 0.002). Similarly visually assessed angiographic stenosis showed a significant increase in the restenotic group (8.6 +/- 0.56 vs. 8.0 +/- 0.61 fl, P = 0.001). The relative odds for developing clinically defined restenosis were 10.2 times greater if the pre-procedural MPV lay in the upper compared to the lowest quartile. There was a positive correlation between MPV and change in minimal luminal diameter between post angioplasty and follow-up angiography, assessed quantitatively, r = +0.56, P = 0.016. There was no association between clinical or angiographic definitions of restenosis and haemoglobin, red cell count, mean corpuscular volume, white cell count or platelet count. Platelet size may influence the development of restenosis after successful coronary angioplasty. PMID- 8344337 TI - Changes in biological activity and immunoreactive mass of lipoprotein lipase in congenital nephrosis: relationship to hypertriglyceridaemia. AB - The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglyceride catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P < 0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r = 0.72, P < 0.05) and between plasma FFA concentrations and serum albumin concentrations (r = -0.73, P < 0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C-II (apo C II) and apoprotein C-III (apo C-III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C II/C-III was significantly lower than the mean in controls (P < 0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disintegrity of the VLDL-IDL-LDL delipidation cascade in children with CNF. PMID- 8344338 TI - CD23 and CD21 function as adhesion molecules in homotypic aggregation of human B lymphocytes. AB - We have previously found that interleukin-4 and CD40 monoclonal antibodies (mAb) are strong potentiators of homotypic B cell aggregation which is dependent on LFA 1. We show here that CD23 mAb were also able to inhibit aggregation to a similar extent as LFA-1 antibodies. This inhibition was restricted to the MHM6 epitope of CD23 and antibodies to other epitopes [Epstein-Barr virus (EBV) CS-1, EBV CS-2, EBV CS-5 and mAb 25] or occupation of the Fc-binding site by IgE had no or a slightly enhancing effect on aggregation. When testing two antibodies to CD21, the recently defined ligand for CD23, one of these (BU32) was found to be inhibitory whereas the other (THB5) had no effect. By combining antibodies to LFA 1 and CD23, aggregation was often completely inhibited. These data suggest that LFA-1/ICAM-1 and CD23/CD21 are the major molecules involved in homotypic aggregation of human B cells. PMID- 8344339 TI - A soluble, single-chain Kd molecule produced by yeast selects a peptide repertoire indistinguishable from that of cell-surface-associated Kd. AB - Peptide binding to a soluble, single-chain Kd protein produced by the yeast strain Kluyveromyces lactis, and to Kd molecules on Kd-expressing cells (P815) was studied using radiolabeled Kd-restricted peptides. The stability of the peptide-Kd complexes formed was monitored in the absence and presence of unlabeled competitor peptides. Radioiodination of the Tyr anchor residue in position 2 of the peptide interferes with binding. A Kd-biased peptide library and a modified antigenic peptide in which a second Tyr was added in positions 6 and 8, respectively, were therefore used to assay binding. Recombinant and cell associated Kd molecules are very similar in the following respects: the ease with which the proteins can be loaded with labeled peptide; the spectrum of peptides selected from a peptide library; the stability of the labeled peptide-Kd complex formed; and the ability to partially dissociate the class I-peptide complex with exogenous, unlabeled peptides. These results imply that measurements of peptide binding to soluble Kd molecules are a reliable indicator of the peptide-binding properties of Kd proteins on living cells. The large quantities of soluble recombinant Kd protein currently available represent an invaluable tool not only for dissecting the molecular mechanisms of antigen presentation but also for vaccinations and the design of T cell-specific toxins. PMID- 8344340 TI - Protection from insulin-dependent diabetes mellitus is linked to a peptide transporter gene. AB - HLA class II association with insulin-dependent diabetes mellitus (IDDM) is well established but is still difficult to map to a particular locus. Polymorphism of the genes coding for transporter associated with antigen processing (TAP1 and TAP2), and located in the HLA class II region, was studied in 167 IDDM patients (116 adult-onset and 51 childhood-onset patients) and 98 normal controls using oligotyping after genomic amplification. A dominant protective effect was observed for the TAP2*0201 allele [relative risk (RR) = 0.3, corrected probability (pc) < 0.001]. Conversely, susceptibility to IDDM was associated with apparent homozygosity for the TAP2*0101 allele (RR = 3.4, pc < 0.001). Protection was independent from but additive to the protection conferred by the DRB1*02 DQB1*0602 haplotype (RR = 0.06, pc < 0.05), and antagonistic to the DRB1*03 DQB1*0201 and DRB1*04 DQB1*0302 haplotypes predisposing effect (RR = 1.1, not significant), arguing in favor of an absence of linkage disequilibrium between TAP2 and HLA class II genes. This was assessed by chi 2 analysis. TAP1 allelic distribution was not different among diabetics and controls. A significant association was observed between the presence of TAP2*0101 and that of islet cell antibodies (p < 0.05). These data suggest that the TAP2 gene, which encodes protein required for delivery of antigen peptides to class I molecules in the endoplasmic reticulum, could modulate the autoimmune response leading to beta cell destruction. From a practical point of view, they make the combined screening of HLA class II and TAP2 loci a highly valuable tool in IDDM prediction. PMID- 8344341 TI - Methylation status of immunoglobulin kappa gene segments correlates with their recombination potential. AB - We have previously shown that unlike endogenous chi genes, unrearranged chi transgenes undergo V chi-J chi recombination in Tas well as B cells of transgenic mice. To determine whether the difference in recombination specificity of the transgenic and endogenous chi genes is associated with differences in DNA structure, the methylation status of the endogenous genes and three unrearranged chi transgenes was compared. The J chi-C chi locus of the transgenes was found to be hypomethylated in all tissues of the transgenic mice. In contrast, methylation of the endogenous chi genes was tissue and developmentally regulated. Hypomethylation of the endogenous J chi-C chi region occurs only in cells of the B lineage undergoing, or having completed chi gene recombination. Transfection of fibroblasts from transgenic and control mice with the recombination activating genes, Rag1 and Rag2, led to a high level of rearrangement of the hypomethylated transgenic, but not the endogenous chi genes. These results suggest that hypomethylation defines an accessible state of the chi locus and that methylation/demethylation could be involved in the control of chi gene rearrangement during lymphocyte differentiation. PMID- 8344342 TI - Cytokine production and heterogeneity of primary stromal cells that support B lymphopoiesis. AB - Many reports document that bone marrow stromal cells or their cytokine products can influence the formation of B cells in vitro. Most of this data comes from studies using lines or clones of stromal cells after multiple passage in culture, which could alter gene expression. Our aim in the present study was to determine which cytokines are produced by normal stromal cells under conditions that promote B lymphopoiesis. Primary cultured stromal cells were isolated on FACS from active Whitlock cultures. These cells proved to be relatively homogeneous in expression of cell surface antigens (CD44, VCAM-1, MECA10, and a molecule marked by hamster anti-mouse 8.28 monoclonal antibody). RNA from unselected Whitlock cultured adherent cells and sorted stromal cells from the same cultures were subjected to reverse transcriptase polymerase chain reaction to assess constitutive expression of several cytokine genes. Transcripts for interleukin-1 beta (IL-1 beta), IL-7, macrophage (M)-colony-stimulating factor (CSF), stem cell growth factor (SCGF), insulin-like growth factor 1 (IGF-1) and occasionally leukemia inhibitory factor were detected in RNA from intact cultures. Messages for IL-7, M-CSF, and SCGF were selectively contained within the isolated stromal cell fraction; whereas, IL-1 beta was found solely within the non-stromal cell fraction. IGF-1 was transcribed by both stromal cells and macrophages in Whitlock cultures. No evidence was found for constitutive expression of IL-1 alpha, IL-4, IL-6, or granulocyte-macrophage-CSF. This is in contrast to some reported stromal cell lines and clones. To determine if all primary stromal cells from active lymphopoietic cultures produced IL-7, the isolated cells were stained to reveal cytoplasmic IL-7 protein. A majority of the cells produced IL-7, but about 20% had no detectable IL-7 protein. Taken together, our results suggest that the primary stromal cells are a distinguishable cell type but functional subsets may exist. In regard to the differences in IL-7 production, the primary cell phenotype appears to mirror at least one division noted among the stromal cell lines. PMID- 8344343 TI - Thymus-derived cytokine(s) including interleukin-7 induce increase of T cell receptor alpha/beta+ CD4-CD8- T cells which are extrathymically differentiated in athymic nude mice. AB - Extrathymic T cell differentiation pathways have been reported, although the thymus is the main site of T cell differentiation. The thymus is also known to produce several cytokines that induce proliferation of thymocytes. In the present study, we investigated the influence of thymus-derived cytokines on extrathymic T cell differentiation by intraperitoneal implantation with a diffusion chamber which encloses fetal thymus (we named it fetal thymus-enclosed diffusion chamber, FTEDC) in athymic BALB/c nu/nu mice. Increase in number of T cells bearing T cell receptor (TcR) alpha/beta was detected in lymph nodes and spleens of FTEDC implanted nude mice 1 week after implantation, whereas no such increase was detected in control nude mice implanted with a diffusion chamber without thymus. The FTEDC-induced increase of T cells was suppressed by intraperitoneal injection of anti-interleukin-7 monoclonal antibody (mAb). The TcR alpha/beta T cells in FTEDC-implanted BALB/c nu/nu mice preferentially expressed V beta 11, although V beta 11-positive T cells are deleted in the thymus of euthymic BALB/c mice by clonal elimination of self-super-antigen Dvb11-specific T cells. TcR alpha/beta T cells in FTEDC-implanted nude mice were of CD4-CD8- phenotype and showed no proliferative response against anti-TcR monoclonal antibody stimulation. These results suggest that the thymus can induce extrathymic T cell differentiation through the influence of thymus-derived cytokine(s) including interleukin-7, and that such extrathymically differentiated T cells have acquired only a little or no ability for proliferation when they recognize antigen by their TcR. PMID- 8344344 TI - Bacterial expression of a single-chain Fv fragment which efficiently protects the acetylcholine receptor against antigenic modulation caused by myasthenic antibodies. AB - Monoclonal antibodies (mAb) against the main immunogenic region (MIR) of the acetylcholine receptor (AChR) are very potent in inducing antigenic modulation of the AChR in animals and in muscle cell cultures. A recombinant antibody fragment of the rat anti-MIR mAb198 was cloned by polymerase chain reaction and expressed as soluble single-chain Fv fragment (scFv198) in E. coli and affinity purified. DNA sequencing was used to define the VH (IB) and VL (K2) chain gene usage. scFv198 was found immunologically and biologically active. Its binding affinity for the Torpedo AChR (KD = 2 +/- 0.6 nM) was very similar with that of the intact mAb198 (KD = 1.8 +/- 0.6 nM) while for the human AChR (KD = 80.7 +/- 16.6 nM) it was about four times lower than that of the intact mAb198 (KD = 21.6 +/- 6.6 nM). This fragment was capable of efficiently protecting the AChR in human cell cultures, against antigenic modulation caused by the intact mAb198 or by the antibodies from a myasthenic patient. The produced scFv198 fragment is, therefore, potentially useful in therapeutic applications for myasthenia gravis after appropriate genetic manipulations. PMID- 8344345 TI - Expansion of the CD4-, CD8- gamma delta T cell subset in the spleens of mice during non-lethal blood-stage malaria. AB - Splenic gamma delta T cells (CD4-, CD8-) increased more than 10-fold upon resolution of either Plasmodium chabaudi adami or P.c. chabaudi infections in C57BL/6 mice compared to controls. Similarly, a 10- to 20-fold expansion of the gamma delta T cell population was observed in beta 2-microglobulin deficient (beta 2-m0/0) mice that had resolved P.c. adami, P.c. chabaudi or P. yoelii yoelii infections. In contrast, increases in the number of splenic alpha beta T cells in these infected mice were only two to three-fold indicating a differential expansion of the gamma delta T cell subset during malaria. Because nucleated cells of beta 2-m0/0 mice lack surface expression of major histocompatibility complex class I and class Ib glycoproteins, our findings suggest that antigen presentation by these glycoproteins is not necessary for the increasing number of gamma delta T cells. Our observation that after resolution of P.c. adami malaria, C57BL/6 mice depleted of CD8+ cells by monoclonal antibody treatment had lower numbers of gamma delta T cells than untreated controls suggests that the demonstrated lack of CD8+ cells in beta 2-m0/0 mice does not contribute to the expansion of the gamma delta T cell population during non lethal malaria. PMID- 8344346 TI - Evaluation of functional heterogeneity in the CD8 subset with T cells from T cell receptor-transgenic mice. AB - The question of functional differentiation within the CD8 subset has been addressed in a model of TcR-transgenic (TcR-tg) mice expressing a TcR specific for H-2Kb (Ti). CD8+ Ti+ T cells present in the periphery of these mice have no cytotoxic T lymphocyte (CTL) activity unless they are stimulated with H-2Kb expressing cells. In contrast to T cells from normal H-2k littermates, alloantigen induction of CTL from TcR-tg mice is independent of CD4+ T helper (Th) cells and is accompanied by high level secretion of interleukin-(IL)-2 by Ti+ CD8+ T cells. Precursor frequency analysis performed on CD8+ cells from TcR tg mice revealed a high frequency of Th as compared to CTL precursors. This raised the possibility of the existence of distinct subpopulations within CD8+ precursors with different requirements for differentiation to functional CTL. FACS analyses (performed on resting and on in vitro stimulated T cells from normal and TcR-tg mice) demonstrated a heterogeneous expression of Ly-6C on CD8+ cells with a large enrichment of Ly-6C- cells among the Ti+ cells which persisted after stimulation with H-2b cells in conditions that led to a homogeneous expression of the activation markers pgp-1 and CD69. The possibility that Ly-6C expression could mark functionally different subpopulations in CD8+ T cells was investigated. Stimulation of sorted populations of Ly-6C- and Ly-6C+ cells allowed detection of CTL precursors in both these subsets and the majority of limiting dilution wells containing one pCTL also scored positive for IL-2 secretion. Thus, for CD8+ T cells expressing the same TcR, differentiation led to acquisition of both IL-2 secretion and CTL function and there was no evidence for the existence of a distinct population of helper-dependent CTL precursors. PMID- 8344347 TI - Signaling through the LFA-1 leucocyte integrin actively regulates intercellular adhesion and tumor necrosis factor-alpha production in natural killer cells. AB - The LFA-1 leucocyte integrin is known to participate in natural killer (NK) cytolytic activity, mediating effector target interactions. The possibility that LFA-1 may also play an active regulatory role in NK cells has been explored. To this end, we have employed a monoclonal antibody (HP1N) raised against recombinant interleukin-2 (rIL-2)-activated NK cells, which recognizes the alpha chain of the LFA-1 heterodimer (CD11a). In contrast to other anti-CD11a mAb the HP1N and its F(ab')2 fragment did not affect NK cell-mediated cytotoxicity and triggered a strong homotypic adhesion of NK cells and other LFA-1+ cells. Cellular aggregation was inhibited by anti-CD18 mAb, anti-ICAM-1 mAb, and other anti-CD11a mAb. Remarkably, the HP1N mAb was also shown to induce tumor necrosis factor-alpha (TNF-alpha) production from NK cells upon costimulation with anti CD16 mAb. Such an effect appeared to be independent from homotypic adhesion since it took place in Mg(2+)-free medium, where NK cell aggregation was inhibited. Moreover, incubation with the HP1N mAb triggered a Ca2+ influx into the cytosol; this effect was clearly observed upon cross-linking of cell bound HP1N and was also substantiated with other anti LFA-1 (CD11a and CD18) mAb. Taken together these results indicate that the LFA-1 molecule is capable of transducing signals in NK cells, which regulate the intercellular interaction with its ligand, and enhance the activation via Fc gamma receptor type III. PMID- 8344349 TI - Regulation of perforin gene expression in a T cell hybrid with inducible cytolytic activity. AB - A mouse x rat T cell hybrid (PC60) that does not require interleukin (IL)-2 for proliferation, was used as a model to study regulation of perforin gene expression. Perforin mRNA is barely detectable in non-induced PC60 cells; however, a 30-fold induction is observed after stimulation with IL-1 alone. Peak perforin mRNA levels were reached after 10 h of induction with IL-1, and these levels were maintained for as long as the stimulus was present. IL-2 by itself has no detectable effect. However, in combination with IL-1 it shows the same induction kinetics as IL-1 alone for the first 10 h, subsequently there is synergism (100-fold induction) between IL-1 and IL-2. The induction response was mainly due to increased transcriptional rates of the perforin gene, and require newly synthesized proteins. The half-life of perforin mRNA in this system is about 5 h. In addition, we confirm the existence of two types of mouse perforin mRNA that differ in their 5' untranslated regions, and show evidence that both mRNA are translated in vivo with similar efficiencies. PMID- 8344348 TI - Association of a 70-kDa tyrosine phosphoprotein with the CD16: zeta: gamma complex expressed in human natural killer cells. AB - The CD16: zeta: gamma receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fc gamma domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of zeta and gamma are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the zeta subunit and the phospholipase C gamma-1 and gamma-2 isoforms. Here we show that CD16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16: zeta: gamma receptor complex, results in the tyrosine phosphorylation of a 70 kDa zeta-associated protein (pp70). Similarly, a 70-kDa zeta-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa zeta-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16: zeta: gamma complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation. PMID- 8344350 TI - Allogeneic recognition of class I molecules: anti-H-2Ld repertoire of H-2b mice includes T cells recognizing mutant class II H-2b (Abm12) molecules. AB - Two major histocompatibility complex (MHC) class I-reactive T cell clones derived from H-2b mice, generated against the allogeneic Ld molecule, were found to recognize the H-2b class II mutant Abm12 molecule as well. In addition, these clones also recognize the class II A(s) molecule, and display a class II dependent reactivity to staphylococcal enterotoxin B. Neither the class I nor the class II alloreactivities of the clones were found to be dependent on other MHC molecules. Both clones express CD4+CD8- phenotypes. The CD4 molecule appears to be involved in their class II reactivity, while little or no role for CD4 could be detected in the class I reactivity. This is the first report of a class I/class II cross-reactivity being mediated by CD4+ T cells. The structural basis for this cross-reactivity is discussed. PMID- 8344351 TI - Cachexia and the acute-phase protein response in inflammation are regulated by interleukin-6. AB - Cachexia and the acute-phase response are common manifestations of inflammation and are presumed to be the product of increased synthesis and release of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6). IL-1 receptor blockade has been previously shown to attenuate the weight loss, anorexia and acute-phase protein responses associated with a turpentine abscess. However, IL-1 receptor blockade was also associated with a reduced plasma IL-6 response, suggesting that the benefit achieved by IL-1 receptor blockade may be mediated by reduced systemic IL-6 production. To gain a better understanding of the role of IL-6 in this model of inflammation, C57BL/6 mice were passively immunized with either a monoclonal anti-IL-6 antibody (20F3), an anti-IL-1 type I receptor monoclonal antibody (35F5), a non-immune rat IgG, or a combined therapy of 35F5 and 20F3, before receiving a sterile turpentine abscess. IL-6 or IL-1 receptor blockade equally spared body weight and food intake. Compared to IL-1 receptor blockade, passive immunization against IL-6 further reduced the hepatic acute-phase protein response, as represented by serum amyloid P and complement 3. Combined blockade of IL-6 and IL-1 receptor did not result in a further sparing of body weights or improvement of food intake. These results confirm that IL-1 contributes to host cachexia and the acute-phase response following a turpentine abscess, but also show that these actions are dependent upon an IL-6 response. We conclude that the influence of IL-1 on cachexia and the acute-phase response is mediated, at least in part, through IL-6 and, thus, IL-6 may play a pivotal role in the cachexia and acute-phase response to inflammation. PMID- 8344352 TI - The expressed T cell receptor V gene repertoire of rheumatoid arthritis monozygotic twins: rapid analysis by anchored polymerase chain reaction and enzyme-linked immunosorbent assay. AB - Because of heterogeneity in the outbred human population, it has been difficult to determine the genetic factors that influence the expressed T cell receptor (TcR) repertoire in autoimmune diseases. To overcome this problem, we have developed a combination of anchored polymerase chain reaction (APCR) and enzyme linked immunosorbent assay (ELISA) that can accurately assess TcR V gene frequencies in numerous clinical samples. The results are independent of amplification efficiency, and V gene usage can be readily analyzed with an ELISA plate reader and associated software. Using this method, the TcR V beta gene repertoires in peripheral lymphocytes from nine sets of identical twins, normal, concordant or discordant for rheumatoid arthritis (RA), were studied. The TcR V beta results were compared with TcR V gamma frequencies in the same specimens as determined by APCR-ELISA and cDNA sequence analysis. The results showed a marked similarity in the TcR V beta gene repertoires between identical twins, compared to unrelated subjects (p < 0.05) whether or not they were concordant or discordant for RA. In contrast, the TcR V gamma gene repertoires in the monozygotic twins differed as much as in controls. The data imply that (a) the human TcR V beta gene repertoire in peripheral blood is genetically controlled, whereas (b) the TcR V gamma gene repertoire is primarily influenced by environmental stimuli, and (c) RA causes no consistent change in TcR V beta repertoire of peripheral blood. The APCR-ELISA method, in the context of large scale family and population studies, should facilitate a more precise delineation of the genetic factors that regulate human TcR V beta expression. PMID- 8344353 TI - Fc epsilon receptor-positive cells are a major source of antigen-induced interleukin-4 in spleens of mice infected with Schistosoma mansoni. AB - When cultured in vitro with either mitogen or parasite antigens, spleen cells from mice infected with Schistosoma mansoni produce significantly higher levels of IL-4 than splenocytes from control animals. Previous studies suggested that this increase in IL-4 production occurs because of a selective expansion of T helper type 2 (Th2) cells in infected mice. However, these experiments employed unfractionated spleen populations rather than purified T lymphocytes. Here we demonstrate that T-depleted spleen cells from infected animals synthesize high levels of interleukin-4 (IL-4), but no IL-5 when stimulated with parasite antigen in vitro. Nevertheless, when purified by sorting, T cells and non-B, non-T (NBNT) populations produced similar amounts of IL-4 in response to parasite antigen. The IL-4 producing NBNT cells were found to belong to an Fc epsilon receptor (Fc epsilon R)-positive population which after sort purification produced high levels of IL-4 (between 1000 and 2000 U of per 5 x 10(3) cells). FACS analysis revealed that these Fc epsilon R+ cells make up 0.53% of splenic NBNT cells in control animals while in 8-9-week-infected animals they increase to 3.8% of that population. In contrast, in mice with 8-week unisexual worm infections these cells comprise only 1.71% of NBNT cells, indicating that eggs are a major stimulus of the response. The expansion of Fc epsilon R+ cells and their production of IL-4 could be an important factor regulating the selection and induction of different CD4+ subsets in schistosome-infected hosts. PMID- 8344354 TI - The intronic immunoglobulin kappa gene enhancer acts independently on rearrangement and on transcription. AB - It is not known which cis-acting elements regulate kappa gene rearrangement. However, the onset of rearrangement coincides with the onset of transcription suggesting that common regulatory elements are used. We have investigated the role of the intronic enhancer on rearrangement using mice transgenic for kappa minigenes. The rabbit kappa enhancer, which is defective in activation of transcription in mouse cells, allows a high level of rearrangement. However, transgenes which possess no enhancer region at all are rearranged a hundred times less compared to transgenes which possess the rabbit enhancer. Our results suggest that while the enhancer region can activate rearrangement as well as transcription, its action on both phenomena can be uncoupled. PMID- 8344355 TI - Regulation of T cell production in T cell receptor transgenic mice. AB - The thymus produces many more cells than it releases into the periphery. According to generally accepted models of T cell development most of this loss occurs in the thymic cortex, among CD4+8+ thymocytes. An interesting situation arises in the case of T cell receptor (TcR) transgenic mice in which all cells can potentially be positively selected, leading to a theoretical increase of about 30-fold in the survival rate of CD4+8+ cells and in their transition to mature CD4+8- or CD4-8+ thymocytes. This in turn should lead to a 30-fold increase in the size of the thymic medulla, in the emigration rate and in the size of the peripheral T cell pool. Increases in medullary or peripheral pool sizes of this magnitude are not seen in TcR transgenic mice. The question was therefore asked whether some form of homeostatic process regulated the size of the mature T cell pool and at what level it might operate. In this report we demonstrate that the increased rate of double-positive to single-positive transition in the TcR transgenic mice is directly reflected in an increased emigration rate, and that the medulla seems to be relatively efficient regardless of the number of cells passing through it. However, the potential increases in emigrant numbers in TcR transgenic mice are offset by the reduced size of the CD4+8+ thymocyte pool. It would appear then that regulation of T cell production, if it occurs, probably does so through regulation of the size of the CD4+8+ thymocyte pool. Mechanisms for regulation of this kind are not yet known. PMID- 8344356 TI - Expression of immunoglobulin kappa and lambda chains in mink. AB - The ratio of kappa and lambda chains of immunoglobulins varies significantly from one species to another. It has previously been thought that lambda was only type expressed in mink. We tested mink immunoglobulin light chains using two monoclonal antibodies G80 and G88. It has been shown that G80 and G88 specifically recognize two antigenically different subpopulations of the light chains. Immunochemical analysis of these subpopulations separated by affinity chromatography suggested that they represent lambda and kappa types of light chains, respectively. Screening of a mink cDNA library with monoclonal antibody G88 resulted in the isolation of clone pIGK-1 containing kappa chain-encoding sequence. The cDNA insert of pIGK-1 included most of the V segment, as well as the J, C and 3' untranslated sequences. Mink V kappa sequence shown the highest homology with the human V kappa II subgroup genes (76-79%). Mink C kappa sequence was 53-63% homologous to C kappa of other species. The striking feature of mink C kappa chain is the presence of glutamine in the C-terminal position. Southern blot analysis suggested that mink haploid genome has one C kappa gene and multiple V kappa genes. The kappa:lambda chain ratio in the 12 minks studied was, on the average, 46:54. The same ratio was observed for the kappa- and lambda producing cells in the mesenteric lymph nodes. The five previously identified mink light chain allotypes were assigned to the lambda chains, thereby confirming that lambda chains in this species are additionally subdivided into several subtypes. PMID- 8344357 TI - Role of liver endothelial and Kupffer cells in clearance of human C1q in rats. AB - In the present study the contribution of rat liver endothelial cells (EC) and Kupffer cells (KC) in the clearance of human (hu) C1q in rats was investigated. In untreated rats and rats depleted from KC the clearance kinetics and the tissue distribution of hu C1q were measured. In untreated rats, the clearance of hu C1q occurred in a monophasic manner with a half-life of 66 +/- 26.7 min. The clearance of hu C1q in KC-depleted rats was delayed significantly (p < 0.001) and occurred with a half-life of 217 +/- 78.8 min. Fifteen min after injection, 11 +/ 3.5% of hu C1q was found in the liver of untreated rats and 8 +/- 1.4% was found in the liver of KC-depleted rats. The percentage non-trichloroacetic acid precipitable activity in the circulation, as a measure for degradation of C1q, reached a level of 11.6 +/- 5.6% at 240 min in untreated rats compared with 4.6 +/- 5.8% in KC-depleted rats. Double immunofluorescence staining 5 min after administration of C1q in untreated rats, revealed that C1q was associated with KC and EC in the liver. Fifteen minutes after i.v. injection of hu C1q, there was an uptake of C1q in the hepatocytes. In KC-depleted rats, 5 min after administration of hu C1q, C1q was bound to the EC. Fifteen minutes after injection, C1q was also found in the hepatocytes. Electron microscopical studies revealed that C1q binds to EC, and that it is internalized in the hepatocytes and KC. The clearance of hu C1q in untreated rats was inhibited by preadministration of high concentrations of bovine C1q. These data show that rats depleted from KC are able to bind, internalize and degrade C1q, and that EC may play a role in the handling of C1q and C1q bound to immune complexes. PMID- 8344358 TI - Characterization and purification of T lymphocyte aminopeptidase B: a putative marker of T cell activation. AB - We have previously described that human T lymphocytes express membrane-associated peptidase activities (Mari et al., EMBO J., 1992, 11:3875). We show in this report that intact Jurkat T cells readily cleaved H-Arg-paranitroanilide, an aminopeptidase B (AP-B) substrate. The identification of the hydrolyzing activity as AP-B was confirmed by its sensitivity to both arphamenine B and bestatin in the nanomolar range. Significant AP-B activity was released in the supernatant upon incubation of intact T lymphocytes at 37 degrees C. However, AP-B activity was found mainly in the cytosolic fraction of Jurkat T cells. Cytosolic T cell AP B was purified to homogeneity and exhibited a molecular mass of 72 kDa. Purified AP-B cleaved N-terminal basic amino acid-containing peptides such as thymopentin (H-Arg-Lys-Asp-Val-Tyr-OH), indicating that it might play a role in the regulation of the concentration of important soluble mediators of T cell activation. A rabbit polyclonal antibody was shown to recognize AP-B as assessed by both immunoprecipitation and Western blot experiments. Finally, we found that AP-B was up-regulated during activation of normal and leukemic T lymphocytes. PMID- 8344359 TI - T cell immunity after a viral infection versus T cell tolerance induced by soluble viral peptides. AB - The fate of in vivo activated CD8+ cytotoxic T cells was studied in transgenic mice expressing a T cell receptor (TCR) specific for the lymphocytic choriomeningitis virus (LCMV) glycoprotein peptide 33-41 presented by major histocompatibility complex (MHC) class I molecules. LCMV infection of TCR transgenic mice induced LCMV-specific effector and memory T cells whereas injection of soluble LCMV glycoprotein peptide 33-41 resulted in tolerance by peripheral deletion and anergy of LCMV-specific T cells after an initial expansion phase. Similarly, LCMV peptide 33-41-specific tolerance could be achieved in normal C57BL/6 mice and was not abrogated by an LCMV infection. These results obtained with a classically MHC-restricted peptide antigen parallel previous findings with retroviral or bacterial superantigens and indicate a possibility to modulate specifically mature peripheral cytotoxic T lymphocytes in vivo. PMID- 8344360 TI - CD4+8- help prevents rapid deletion of CD8+ cells after a transient response to antigen. AB - We have followed the fate of mature CD8+ T cells with a male-specific transgenic T cell receptor after antigenic stimulation with hemopoietic cells in the absence or presence of help. Our data show that mature CD8+ T cells can be deleted after a 3-week period of transient activation and that help, e.g. in the form of interleukin-2, can considerably delay the deletion. These experiments have implications for the design of protocols aiming at the establishment of specific immunological tolerance in T cells. PMID- 8344361 TI - Thymus influences the development of extrathymically derived intestinal intraepithelial lymphocytes. AB - Overwhelming evidence suggests that the majority of murine small intestinal intraepithelial lymphocytes (IEL) are extrathymically derived. These IEL include those with T cell receptor (TCR) gamma delta and some TCR alpha beta (CD8 alpha alpha and Thy-1-). In contrast, congenitally athymic nude mice have low numbers of gamma delta TCR IEL as well as very few alpha beta TCR IEL, far less than that would be expected if one assumes that gamma delta TCR IEL and alpha beta TCR (CD8 alpha alpha and Thy-1-) IEL in euthymic mice are extrathymically derived. To examine this discrepancy, we followed extrathymic IEL differentiation in IEL of day 3-thymectomized (NTX) mice as another athymic mouse model and found that gamma delta TCR IEL and extrathymically derived alpha beta TCR IEL in NTX mice are markedly reduced, almost to the level of nude mice. We further show that it is probably the absence of a thymic stroma that is responsible for the lower amounts of extrathymically derived IEL in nude mice, as the low amounts can be corrected to euthymic levels by syngeneic fetal thymus grafting but not by direct injection of F1 thymocytes. Lastly, unlike TCR/CD3+ extrathymically derived IEL, we noted a large proportion of extrathymic CD3-CD8- and CD3-CD8+ IEL; they were threefold more frequent in nude and NTX than in euthymic mice. This suggests that the thymus influences extrathymically derived IEL in its development from CD3- to CD3+ at the small intestinal epithelium. PMID- 8344362 TI - Pairing of VH gene families with the lambda 1 light chain: evidence for a non stochastic association. AB - The frequencies at which four VH gene families pair with the lambda 1 light (L) chain were determined by sequential hybridization of VH- and lambda 1-specific DNA probes to mitogen-induced colonies of B cells. Analysis of pair frequencies indicates that the repertoire of lambda L chain antibodies is generated by the stochastic pairing of smaller 3'-to-mid-locus VH gene families (X-24, S107, Q52). However, the large 5' VH J558 family appeared to associate with the lambda 1 L chain non-stochastically; the frequency of VHJ558/lambda 1+ colonies among all lambda 1+ colonies was significantly lower than the frequency of J558 expression among all (C mu+) B cell colonies. This difference suggests that selection, either intrinsic at the level of rearrangement or heavy and L chain pairing, or extrinsic following surface immunoglobulin expression, may operate to shape the lambda antibody repertoire prior to the introduction of exogenous antigen. PMID- 8344363 TI - Diversity of expressed V and J regions of immunoglobulin light chains in Xenopus laevis. AB - In Xenopus laevis, two immunoglobulin light chain isotypes, designated L1 or rho and L2 or sigma, have been identified. The genomic organization of the L1 locus has been described previously: a constant (C) gene segment is preceded by a joining (J) gene segment; in addition, there are many cross-hybridizing variable (V) gene segments. To evaluate the extent of sequence diversity of L1 V regions, we screened three cDNA libraries, constructed from mitogen-stimulated Xenopus splenocytes, with probes for the C or the J gene segment. Eighteen cDNA clones that contain complete or truncated V regions were chosen for sequence analysis. The C regions of all clones are identical or nearly identical to the genomic C gene segment; the V regions are greater than 80% identical in nucleotide sequence and are presumably derived from a single family of V gene segments. Although framework regions are nearly identical, complementarity-determining regions are quite diverse. The expressed J segments fall into distinct groups, suggesting the presence of more than one germ-line J segment. Therefore, a genomic library was screened with a J region probe. A clone overlapping with the previously identified J-C clone, and containing four additional J gene segments, was isolated. All five J gene segments are very similar and three are identical in nucleotide sequence. Each of the three distinct germ-line J sequences is represented in the set of cDNA clones, suggesting that combinatorial diversification occurs; imprecision of V-J joining also appears to contribute to variability. Overall, these results suggest that the immunoglobulin repertoire in this species is not significantly restricted by a limitation in the diversity of light chain V regions. PMID- 8344364 TI - An antigen processing polymorphism revealed by HLA-B8-restricted cytotoxic T lymphocytes which does not correlate with TAP gene polymorphism. AB - In previous studies of antigen presentation through HLA-B27, we identified a healthy person whose lymphoblastoid cells do not present three B27-restricted viral epitopes to specific cytotoxic T lymphocytes (CTL), despite adequate cell surface expression of HLA-B2702 of normal sequence. Similar findings were observed in all members of his family sharing the HLA-A3-B2702 haplotype. The original donor, NW, carries HLA-B8 on his other class I haplotype, which his daughter, HW, has inherited. We now report a failure to present an HLA-B8 restricted epitope from influenza nucleoprotein following viral infection of NW cells, although exogenous added peptide is still presented normally. However, cells from HW, which do not carry the A3-B2702 haplotype, present the expected epitope after viral infection. Another B8-restricted epitope, from human immunodeficiency virus-gag, is presented equally well by both cell lines when infected with gag-vaccinia. This antigen processing phenotype does not correlate with any of the known human TAP-1 and TAP-2 polymorphisms. PMID- 8344365 TI - Variable binding affinities of listeriolysin O peptides for the H-2Kd class I molecule. AB - Previously we used the peptide-binding motif for the murine class I major histocompatibility complex molecule H-2Kd to identify a nonamer peptide of the Listeria monocytogenes listeriolysin (LLO) protein that was recognized by cytotoxic T lymphocytes (CTL) in association with H-2Kd. Eleven nonamer peptides contained in the LLO sequence were synthesized and one, LLO 91-99, proved to be a CTL target. Using peptide binding competition assays with H-2Kd-restricted CTL, we show that 3 out of the 11 LLO peptides, including the CTL epitope, have a high binding affinity for H-2Kd; 2 of 11 peptides have approximately 10-fold lower affinity, while the remaining 6 peptides have no or very low affinity for H-2Kd. Single residue changes were made in the LLO 91-99 peptide and two other LLO peptides to identify non-anchor amino acids that might interfere with peptide binding. In addition, we used the LLO peptides which bound well to H-2Kd to attempt to restimulate a secondary CTL response from L. monocytogenes-primed spleen cells. Only LLO 91-99 was able to induce such a response. Thus only a fraction of nonamer peptides which fit the original binding motif have a high affinity for the H-2Kd class I molecule, and only a fraction of these serve as CTL epitopes. PMID- 8344366 TI - Differential induction of Egr-1 expression in WEHI-231 sublines does not correlate with apoptosis. AB - To determine whether the absence of inducible Egr-1 expression correlates with apoptosis and growth arrest, we compared the inducible expression of two Egr family members (Egr-1 and Egr-2) in three sublines of WEHI-231. Expression of Egr 2 is induced in all sublines of WEHI-231 following surface immunoglobulin (sIg) cross-linking, but Egr-1 expression is induced in only two. We find that the lack of inducible Egr-1 expression corresponded to an increase in the methylation pattern of the Egr-1 gene. In spite of these differences in Egr-1 expression, all the sublines demonstrate similar inhibition of [3H] thymidine incorporation following anti-Ig treatment. Growth arrest leads to apoptosis in only two of the sublines, but apoptosis does not correlate with the absence of inducible Egr-1 expression. Demethylation, by treatment with 5-azacytidine, in the Egr-1 non expressing subline allows for induction of Egr-1 expression by anti-Ig, but fails to prevent growth arrest and apoptosis. Therefore, we conclude that the lack of Egr-1 expression is not responsible for either the apoptotic response or growth arrest induced by anti-Ig in WEHI-231. PMID- 8344367 TI - Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I alpha 1 peptide-binding domain. AB - Molecular mimicry of major histocompatibility (MHC) antigens by viral glycoproteins has been suggested as one of the possible mechanisms of induction of an autoimmune response by human immunodeficiency viruses. A monoclonal antibody (M38) was previously shown to bind to both human immunodeficiency virus type 1 (HIV-1) gp120 and beta-2 microglobulin-free HLA class I heavy chains encoded by an HLA C allele. Using HLA C recombinant proteins and synthetic peptides, the M38 class I binding site was mapped to a stretch of 44 amino acids of the alpha 1 domain. The amino acid residues recognized are clustered in two non-contiguous regions at positions 66-69 (KYKR) and 79-82 (RKLR) shared by almost all HLA C alleles. On HIV-1 gp120, M38 binds to two non-contiguous sequences (KYK and KAKR) at positions 490-492 and 505-508 located at the edges of a large hydrophobic region that is apparently involved in binding the transmembrane glycoprotein gp41. The C-terminal gp120 M38-reactive region (KAKR) lies within the immunodominant sequence APTKAKRRVVQREKR, against which the majority of HIV-infected individuals produce antibodies. The results indicate that a functionally important region of HIV-1 gp120 shares similar amino acid sequence motifs with the antigen recognition site of most HLA class I C alleles. The molecular mimicry may be the basis for autoimmune responses in HIV infection. PMID- 8344368 TI - Alloactivated cytotoxic T cells recognize the carboxy-terminal domain of human immunodeficiency virus-1 gp120 envelope glycoprotein. AB - Infection with the human immunodeficiency virus (HIV) virus leads to clinical disease in humans but not in chimpanzees. Progression to disease is associated with activation of the immune system followed by loss of T helper cell function and a slow decline in CD4-positive lymphocytes. The presence of autoreactive and cytotoxic cells in humans but not chimpanzees suggests that mechanisms other than, or in addition to, direct virus-induced cell killing, are required for disease to develop. The observed changes are similar to those seen in chronic allogeneic disease. Here we show that a peptide from the carboxy terminus of gp120, predicted to have a structure similar to the major alpha-helices of major histocompatibility complex (MHC) class I and class II, acts as a cytolytic target when presented on syngeneic cells for alloactivated cytotoxic T effector cells. These data add further evidence to the hypothesis that HIV can act as an allostimulant due to its dual properties of CD4 binding and MHC mimicry. The ability to signal nonspecifically through the T cell receptor could explain the initially paradoxical responses of proliferation, anergy and apoptosis. PMID- 8344370 TI - Thermostability analysis of major histocompatibility complex class I molecules by temperature gradient gel electrophoresis. AB - Empty major histocompatibility complex (MHC) class I molecules present on the surface of RMA-S (26 degrees C) cells were loaded with the iodinated peptides APGNYPAL, FAPGNYPAL (SEV-9) and RGYVYQGL (VSV-8), respectively. The thermostability of these peptide-loaded MHC class I molecules was assessed using temperature gradient native polyacrylamide gel electrophoresis. A linear temperature gradient perpendicular to the direction of electrophoresis yielded a graphical representation of the melting of MHC class I molecules. The class I signal disappeared when the peptide melted out of the groove, and gave rise to a second signal due to released peptide. APGNYPAL-loaded class I molecules melted at 11 degrees C with considerable release even at 0 degrees C. VSV-8-loaded class I molecules melted first at 36 degrees C, whereas SEV-9-loaded molecules melted at about 22 degrees C. A discrimination between the binding of SEV-9 to Kb and Db molecules was seen in the melting patterns. Results are discussed in correlation with known crystallographic structures of class I molecules containing peptides in the binding groove. PMID- 8344369 TI - Increased circulating interleukin-6 (IL-6) activity in endotoxin-challenged mice pretreated with anti-IL-6 antibody is due to IL-6 accumulated in antigen-antibody complexes. AB - Mice pretreated with monoclonal anti-interleukin-6 (IL-6) antibody and then challenged with lipopolysaccharide (LPS), paradoxically develop higher levels of circulating biological IL-6 activity, as measured by the hybridoma growth promotion assay, than mice similarly challenged but not pretreated with antibody. Here we provide evidence that this increased biological activity was entirely accounted for by the presence of increased amounts of IL-6 protein, which could be isolated by immunoaffinity chromatography and subsequently visualized after gel electrophoresis. Chromatography on a protein G matrix and a sandwich ELISA allowed to demonstrate that all IL-6 present in the serum was in the form of antigen-antibody complexes. Serum samples of antibody-treated animals which contained the highest biological activity typically contained near equimolar concentrations of IL-6 and antibody. In vitro neutralization tests with pure antibody and IL-6 demonstrated that, with both antibodies tested, more than 1000 fold molar excess of antibody is needed for neutralization in the hybridoma growth assay. It is concluded that increased biological activity in serum of the anti-IL-6 antibody-treated mice is due to sequestration of the endogenous IL-6 in the form of antigen-antibody complexes which, due to the lack of sufficient antibody excess, produce nearly full activity in the hybridoma growth assay. PMID- 8344371 TI - Helper activity of CD4+ alpha beta T cells is required for the avian gamma delta T cell response. AB - We have studied the in vitro activation of chicken gamma delta T cells. Both splenic alpha beta and gamma delta T cells obtained from complete Freund's adjuvant-primed chickens proliferated in vitro when stimulated with mycobacterial sonicate or purified protein derivative of Mycobacterium tuberculosis. When CD4+ cells or alpha beta T cell receptor (TcR)-positive cells were removed, both the proliferation and the blast formation of gamma delta T cells in response to mycobacterial antigens were abrogated. The response was restored if supernatant from concanavalin A (Con A)-activated lymphocyte cultures (CAS) as a source of helper factors was added together with the specific antigen purified protein derivative. The CD4- or alpha beta TcR-depleted cells still proliferated in response to Con A, although a decrease of the response was observed. To analyze the gamma delta T cell response more specifically we stimulated peripheral blood cells with immobilized monoclonal antibodies against T cell receptor. Anti-gamma delta TcR antibody alone did not induce significant proliferation. When CAS was added together with the anti-gamma delta TcR monoclonal antibody, a strong proliferation of gamma delta T cells was observed. In contrast, both V beta 1- and V beta 2-expressing alpha beta T cells proliferated in vitro in response to stimulation with the relevant anti-TcR monoclonal antibody alone. Depletion of either V beta 1+ or V beta 2+ T cell subset alone had no negative effect on the proliferation or blast formation of gamma delta T cells stimulated with mycobacterial antigens. Taken together our results suggest that CD4+ alpha beta T cells (both V beta 1- and V beta 2-expressing) play a role in the activation and response of chicken gamma delta T cells. PMID- 8344372 TI - High IgE secretion capacity of human plasma cells. AB - In accordance with results obtained in another culture system, it has previously been shown that human B cells frequently switch to immunoglobulin E (IgE) when they are co-cultured with irradiated mutant EL4 thymoma cells (which provide a CD40 ligand-mediated B cell activation signal), T cell supernatant and recombinant interleukin (IL)-4. However, because of the potentially severe side effects of IgE, such as anaphylaxis, B cells could have a limited capacity to produce this isotype. The IgE secretion rate of plasma cells is not known. In the present study, we compared the secretion rates for different Ig classes by means of limiting dilution analysis of plasmocytic cells that were harvested after 8 to 9 days from primary EL4/B cell cultures and titrated into secondary cultures in the presence of a cell proliferation-blocking concentration of hydroxyurea. These cells secreted Ig at constant rates for periods of up to 2 weeks; IgE secretion was IL-4 independent. The mean cellular secretion rates were similarly high for IgE (150 pg/cell/24 h) and other isotypes (IgM 273 pg, IgG 112 pg, IgA 136 pg/cell/24 h). In terms of molecules per min this represents 3.3 x 10(5) for IgE versus 1.2 x 10(5) for IgM, 3.1 x 10(5) for IgG and 3.6 x 10(5) for IgA. The relative frequency of IgE-secreting cells was only 0.3% of the total number of Ig secreting cells, suggesting a small size of IgE-producing clones in this in vitro system. Whether this is relevant regarding an in vivo response is not known. Clearly, the Ig secretion capacity of plasma cells would not limit an IgE response in the absence of extrinsic control. PMID- 8344373 TI - The Mycobacterium tuberculosis 71-kDa heat-shock protein induces proliferation and cytokine secretion by murine gut intraepithelial lymphocytes. AB - Murine intraepithelial lymphocytes (IEL) respond poorly to T cell mitogens and to monoclonal antibody stimulation of T cell receptor (TCR)- and CD3- associated molecules. In contrast, we found that a soluble extract of Mycobacterium tuberculosis (Mtb), but not purified protein derivative of tuberculin, induced significant proliferative responses in IEL cultures. The active component was apparently a heat shock protein (HSP), since recombinant 71-kDa HSP from Mtb induced IEL to proliferate, while 65-kDa HSP from M. bovis and M. leprae did not. Both alpha/beta and gamma/delta TCR-enriched IEL gave proliferative responses to 71-kDa HSP. Further, culture supernatants from IEL stimulated with 71-kDa HSP contained elevated levels of interleukin-(IL)-3/granulocyte-macrophage colony stimulating factor, interferon-gamma and IL-6, but not IL-2, IL-4, IL-5 or transforming growth factor-beta. Finally, several IEL T cell clones have been maintained for up to 6 weeks, when stimulated with 71-kDa HSP, IL-2 and feeder cells. Our results show that the 71-kDa HSP of Mtb induces IEL T cells to divide and to secrete cytokines and this may offer a model for cloning and study of IEL T cells in vitro. PMID- 8344374 TI - Electron microscopic localization of ribosomal DNA in rat liver nucleoli by nonisotopic in situ hybridization. AB - We have used postembedding nonisotopic in situ hybridization, with biotinylated rat ribosomal DNA (rDNA) as a probe and streptavidin coupled to 10-nm colloidal gold particles as the detection system, to localize rDNA sequences in rat liver nucleoli at the electron microscopic level. For comparison purposes, immunoelectron microscopy was performed for the detection of DNA. Our results indicate that ribosomal DNA sequences are enriched in the dense fibrillar component of the rat liver nucleolus. These data are discussed in relation to the putative site(s) for transcription of ribosomal genes. PMID- 8344376 TI - Induction of thermotolerance by prostaglandin A in human cells. AB - Cyclopentenone prostaglandins (PGs) induce the synthesis of heat shock proteins (HSPs) in mammalian cells. Since arachidonic acid metabolites are implicated in the control of fever, we investigated the effect of PG treatment on thermal injury in human K562 erythro-leukemia cells. Prostaglandin A1 (PGA1) was found to protect cells after severe heat shock and to induce a thermotolerant state, which persisted for 24-48 h. Prostaglandins of the B, E, and F type were not effective. Kinetics of thermotolerance induction was comparable to heat-induced heat resistance. Establishment of a thermotolerant state was not a direct effect of PGA1, since it was dependent on de novo protein synthesis and was associated with HSP70 induction. This activity of PGA1 could be part of a protective control mechanism during fever. PMID- 8344375 TI - Conservation of the dimeric unit of H2A and H2B histones during the replication cycle. AB - The behavior of H2A and H2B histones during the replication cycle has been investigated. H2A-H2B dimer fractions obtained from MH-134SC cells labeled with suitable precursors were fractionated by rate zonal centrifugation in sucrose gradients containing 2 M NaCl. Labeling for one round of replication cycle with an amino acid mixture enriched with dense isotopes and [3H]lysine as a radioactive marker yielded a distinct peak of dense dimer that sedimented faster than the normal dimer. Similar density labeling of cells did not cause measurable alteration in the sedimentation profile of the preexisting normal dimer marked with [14C]lysine. The data suggest conservation of the bulk of the dimeric unit during the replication cycle. Biological significance of the dimeric behavior of H2A and H2B is discussed in favor of the partially conservative model of histone octamer assembly. PMID- 8344377 TI - Prompt protein glycosylation during acute heat stress. AB - Constitutive patterns of protein synthesis and protein glycosylation are severely disrupted by acute heat stress. Stressed cells respond by preferential synthesis of specific proteins, e.g., the well-known family of heat shock proteins. We observed another response that rapidly occurs during heating periods as short as 10 min at 45 degrees C. During that period, CHO cells began to glycosylate specific proteins, designated as "prompt" stress glycoproteins (P-SG), while constitutive protein glycosylation ceased. Labeling of P-SGs showed a dose response with time and with temperature and appeared regardless of the label used (D-[3H]mannose or D-[3H]glucose). On SDS-PAGE, the major P-SG was characterized by M(r) approximately 67 kDa (P-SG67) and pI = 5.1. Other less prominent P-SGs appeared at M(r) 160, 100, 64, 60, and 47 kDa; incorporated label showed little turnover during 24 h at 37 degrees C. Prompt glycosylation was inhibited by tunicamycin, and label incorporated into P-SGs was sensitive to N-glycosidase F, but not to O-glycosidase. Analysis of enzymatically digested P-SG67 indicated that label had been incorporated into both high-mannose (Man9GlcNAc) and complex type oligosaccharides. Brefeldin A did not eliminate P-SG67 labeling, but caused the further appearance of novel, Brefeldin-associated P-SGs. Labeling of P-SG67 oligosaccharides occurred without significant concomitant protein synthesis, suggesting that addition of labeled oligosaccharides largely occurred on mature, rather than nascent proteins. The functional significance of prompt glycosylation remains to be defined, but we propose that this novel phenomenon is an integral part of the cellular heat stress response. PMID- 8344378 TI - P- and E-cadherin are in separate complexes in cells expressing both cadherins. AB - E- and P-cadherin are members of a family of calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, the transmembrane cadherins self-associate, while intracellularly, they interact with the actin based cytoskeleton. Several intracellular proteins, collectively termed catenins, are tightly associated with E- and P-cadherin. These proteins appear to link the cadherin to the cytoskeleton and have been proposed to be involved in concentrating cadherins at cell-cell adherens junctions. In this paper we report the production of monoclonal antibodies against both alpha- and beta-catenin and use these antibodies to show that in cells simultaneously expressing two different cadherins, E-cadherin and P-cadherin, each cadherin appears to be present in a separate cadherin/catenin complex. PMID- 8344379 TI - Disposition and orientation of ductin (DCCD-reactive vacuolar H(+)-ATPase subunit) in mammalian membrane complexes. AB - The disposition and orientation of mouse ductin (the subunit c of the vacuolar H(+)-ATPase) in gap junctions has been examined. Like the Nephrops norvegicus (arthropod) form, mouse ductin in the intact junctional structure is resistant to high levels of nonspecific proteinase, suggesting that it is for the most part buried in the bilayer. Antisera to an octapeptide near the N-terminus cross-react with ductins in gap junction preparations from four different mouse tissues, from chicken and Xenopus laevis liver, and from N. norvegicus hepatopancreas. The antisera and antibodies, affinity purified against the octapeptide, agglutinate isolated gap junctions, suggesting that the N-terminus is located on the exposed surface, equivalent to the cytoplasmic face of an intercellular gap junction. The antibodies also block dye coupling when injected into cells in culture, confirming the cytoplasmic location of the epitope. The lipophylic reagent dicylohexyl carbodiimide (DCCD), which targets carboxyl groups within the membrane and selectively reacts with ductin in N. norvegicus gap junction preparations, rapidly inhibits junctional communication. Bafilomycin A1, which inhibits V-ATPase and stops vacuolar acidification, does not affect dye coupling, showing that the inhibition seen with antibodies and DCCD is not an indirect consequence of their action on the ductin of V-ATPase. Consistent with this interpretation the anti-peptide antibodies do not bind to intact chromaffin granules or inhibit their V-ATPase activity, but do bind to osmotically disrupted granule membrane. This suggests that ductin has an orientation (N-terminus pointing away from the cytoplasm) in the vacuolar membrane opposite to that in the gap junction membrane. PMID- 8344380 TI - Control of apoptosis and growth of malignant T lymphoma cells by lymph node stromal cells. AB - We have previously established the malignant T lymphoma CS-21 cell line from a spontaneous lymphoma in a BALB/c mouse. CS-21 lymphoma cells grew continuously when they were cocultured with stromal CA-12 cells prepared from lymph nodes. CS 21 lymphoma cells, however, could not proliferate by themselves, and they underwent apoptosis when separated from the stromal CA-12 cells. Apoptosis of CS 21 lymphoma cells was determined by observation of morphological changes using a transmission electron microscope and also by detection of nuclear DNA degradative fragments of oligonucleosomal size. Stromal CA-12 cells secreted soluble factors that enhanced DNA synthesis in CS-21 lymphoma cells. The soluble factors, however, were not sufficient to prevent apoptosis of CS-21 cells. Apoptosis of CS 21 lymphoma cells was suppressed only when the CS-21 lymphoma cells were cocultured with substantial numbers of CA-12 cells. The results suggest that the lymph node stromal CA-12 cells played an important role in the growth of CS-21 lymphoma cells by providing at least two different signals. One signal prevented CS-21 cells from apoptotic cell death by direct cell-to-cell contact, and the other signal enhanced the CS-21 cell proliferation by secreted soluble factors. PMID- 8344381 TI - Negative trans-acting mechanisms controlling expression of platelet-derived growth factor A and B MRNA in somatic cell hybrids. AB - We have studied a human malignant melanoma cell line (WM115) which expresses high levels of PDGFA and PDGFB mRNAs, a hamster fibroblast cell line (Wq3H) which lacks PDGFB and has a very low expression of PDGFA mRNA, and hybrids between these cell lines. The PDGFA and PDGFB mRNA expression in the hybrid cells was markedly suppressed, indicating that the melanoma PDGF genes are controlled in the hybrid cells by negative factors/mechanisms contributed by the fibroblast genome. The melanoma but not the fibroblast PDGFB mRNA was induced by cycloheximide in the hybrid cells, indicating that the fibroblast and the melanoma PDGFB genes are regulated differently despite their presence in the same intracellular environment. PMID- 8344382 TI - Intramitochondrial localization of the main 70-kDa heat-shock cognate protein in Drosophila cells. AB - The main heat shock cognate protein (hsc) of 70 kDa in Drosophila, hsc 4, was localized in cultured cells using a specific affinity-purified antibody and colloidal gold immunoelectron microscopy. This constitutively expressed member of the heat shock protein (hsp) 70 family is found in the cytosol, in mitochondria, and in the nucleus of unstressed cells. The identity of hsc 4 in these three cellular compartments was confirmed by two-dimensional gel immunoblots and partial proteolytic digestion patterns. In mitochondria, the colloidal gold particles are observed in close proximity to or on the inner membranes. The intramitochondrial localization of this hsc was confirmed by density gradient purification and by resistance of hsc 4 to externally added trypsin. In the nucleus, the labeling is found on nucleo-plasmic perichromatin RNP fibrils and is not detected in the nucleolus. Heat shock induces an intracellular redistribution of hsc 4 with an enrichment in the nucleus. The localization of this hsc in different cellular compartments is consistent with the previously suggested functions of some members of this family of proteins in basic cellular processes such as protein folding. Moreover, the present data suggests that the main constitutively expressed member of the hsp 70 family, hsc 4, functions both within the mitochondrial compartment and in the nucleus. PMID- 8344383 TI - Cytoskeletal and cytocontractile protein composition of smooth muscle cells in developing and obstructed rabbit bladder. AB - The differentiation patterns of smooth muscle cells (SMC) in rabbit bladder during development and in the hypertrophic response to partial outflow obstruction induced in adult animals were evaluated by biochemical and immunochemical techniques and by using a panel of monoclonal antibodies specific for desmin, vimentin, alpha-actin of smooth muscle (SM) type, SM myosin, and nonmuscle (NM) myosin isoforms. Desmin and SM alpha-actin were homogeneously distributed in SMC of developing, adult, and obstructed bladders. Conversely, marked changes in the ratio and antigenicity of SM myosin isoforms were observed by SDS electrophoresis and Western blotting, respectively. In particular, the 205 K (SM1) isoform was down-regulated with development whereas the 200 K (SM2) isoform was up-regulated around 7 days after birth and down-regulated in the obstructed bladder. Vimentin was expressed in SMC of the fetal bladder and declined markedly during postnatal, physiological hypertrophy of SMC, which occurs concomitantly with diminution of DNA synthesis. This polypeptide became detectable, however, in SMC of obstructed bladders. The 196 K (NM) myosin isoform recognized by NM-A9 antibody, present only in endothelium of blood vessels and in mucosa of normal fetal and adult bladders, became expressed in detrusor muscle, when SMC underwent a process of pathological hypertrophy. The reexpression of vimentin and the de novo appearance of NM myosin isoform in hypertrophic bladders can be reversed when the tissue mass is reduced, such as in bladders after 1 month recovery from partial obstruction. Thus, a specific NM myosin isoform can be used as a marker of SMC hypertrophy in obstructed bladder. In addition, the combined use of anti-vimentin and NM-A9 antibodies can distinguish between SMC which are in the physiological or in the pathological condition of adaptive bladder hypertrophy. PMID- 8344384 TI - The role of macrophages in skeletal muscle regeneration with particular reference to chemotaxis. AB - The results from this investigation suggest that chemotactic factor(s) from damaged myofibers attract polymorphonuclear leukocytes (PML) and macrophages to the site of injury, while exudate macrophages but not PML induce a strong positive chemotactic response in myogenic cells. The AB and BB isoforms of platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF beta), basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (LIF) (all of these are secreted by macrophages) were also shown to be chemoattractants for muscle precursor cells (MPC). The AA isoform of PDGF did not appear to have any such chemotactic effect on MPC. Macrophages were also shown, under tissue culture conditions, to stimulate the proliferation of MPC. This mitogenic effect was similarly demonstrated for the BB isoform of PDGF, bFGF, and TGF-beta but not for the AA or AB isoforms of PDGF nor for LIF. The results indicate that macrophages play a pivotal role in the orchestration of muscle fiber reconstitution. PMID- 8344385 TI - Constitutive production of macrophage colony-stimulating factor and interleukin-6 by human ovarian surface epithelial cells. AB - Normal and neoplastic epithelial cells produce growth factors that can affect cells from different lineages. Epithelial ovarian cancers produce M-CSF and IL-6. In the present study, production of these cytokines has been measured in the apparently normal epithelial cells from which epithelial ovarian neoplasms are thought to arise. Epithelial cells from the surface of premenopausal human ovaries were established in short-term cultures. The cells bound anti-cytokeratin antibodies and exhibited characteristic epithelial morphology by light and transmission electron microscopy. M-CSF and IL-6 were detected in supernatants from cultures of these cells, using assays specific for each factor. Cytokine levels were comparable to those in supernatants from ovarian and breast cancer cell lines. M-CSF expression could also be demonstrated by immunohistochemical analysis with specific rabbit heteroantiserum. Thus, M-CSF and IL-6 are produced constitutively by normal as well as by neoplastic ovarian epithelium. PMID- 8344386 TI - PKC activity and PKC-alpha mRNA content are reduced in serum-derived human neuroblastoma cells without concomitant induction of differentiation. AB - Protein kinase C (PKC) is a serine/threonine kinase which is thought to play an important role in cellular proliferation and differentiation. PKC activity is stimulated physiologically by diacylglycerol and experimentally by phorbol esters. Long-term exposure of human neuroblastoma cells to phorbol esters results in down-regulation of PKC activity and induction of neuronal differentiation. In this study, we explored the hypothesis that reduced PKC expression is necessary for differentiation of the human neuroblastoma cell line SK-N-SH. PKC activity and PKC-alpha mRNA levels were assayed in cultured SK-N-SH cells over a period of several days in the presence or absence of serum. These determinants of PKC expression were compared with several known markers of neuroblastoma differentiation, including neurite outgrowth and steady-state levels of c-myc and GAP43 mRNA. We observed steady losses of PKC activity and PKC-alpha mRNA content after transfer of cells to serum-free or chemically defined media. However, morphological and biochemical differentiation of SK-N-SH cells occurred only in chemically defined medium, perhaps due to the presence of insulin. We conclude that while loss of PKC may be associated with neuroblastoma differentiation, diminished PKC alone is not sufficient to induce or support the differentiation process. PMID- 8344387 TI - Experimentally provoked neural induction results in an incomplete expression of neuronal traits. AB - In the amphibian embryo, the ectoderm becomes a neural structure during gastrulation as a result of an interaction with the dorsal mesoderm. From that time onward, neurectodermal cells have the ability to express in vitro a large variety of mature phenotypes without further interaction with the inducing tissue. The neuralization of the ectoderm can be reproduced in a variety of experimental situations that do not involve the dorsal mesoderm. In this study we have analyzed biochemically the extent to which artificial inductions mimic the natural inducing process. Making use of antibodies specific to different neurotransmitter pathways, we have shown that the repertoire of the phenotypes expressed by experimentally induced neurons is always restricted compared to those obtained after induction in vivo. Only a limited number of generic neuronal characteristics are expressed. These results suggest that the expression of a complete neuronal phenotype normally involves a sequence of inductive events that can be experimentally uncoupled. PMID- 8344388 TI - Modulation of activin expression by type beta transforming growth factors. AB - Activins are potentially important regulators of early developmental processes in vertebrates. Although the different forms of activin appear to be differentially expressed during early amphibian, avian, and murine development, little is known about the factors that regulate their expression. In this study we report the qualitative effects of several growth and differentiation factors on the expression of inhibin subunits in three differentiated cell lines derived from P19 embryonal carcinoma cells. These cell lines include mesodermal (MES-1), neuroepithelial (EPI-7), and visceral endoderm-like (END-2) cell types, expressing both inhibin beta A and beta B subunit mRNAs. We have shown for the first time that this expression is modulated by transforming growth factor (TGF)beta 1 and TGF beta 2 but not significantly by other growth factors such as leukemia inhibitory factor or members of the fibroblast growth factor family (aFGF, bFGF, or kFGF). beta A mRNA expression is increased while beta B expression is simultaneously decreased by TGF beta. Furthermore, TGF beta increased the amount of bioactive activin secreted by MES-1 and END-2 cells. Inhibin alpha subunit mRNA expression is not affected by TGF beta. These results point to a possible role of type beta transforming growth factors as regulators of activin expression in embryonal cells. PMID- 8344389 TI - Retinoic acid induces rapid mineralization and expression of mineralization related genes in chondrocytes. AB - Numerous studies of experimental hypo- and hypervitaminosis A have long suggested that retinoic acid (RA) is involved in chondrocyte maturation during endochondral ossification and skeletogenesis. However, the specific and direct roles of RA in these complex processes remain unclear. Based on recent studies from our laboratories, we tested the hypothesis that RA induces the expression of genes associated with the terminal mineralization phase of chondrocyte maturation and promotes apatite deposition in the extracellular matrix. Cell populations containing chondrocytes at advanced stages of maturation were isolated from the upper portion of Day 18 chick embryo sterna and grown for 2 weeks in monolayer until confluent. The cells were then treated with low doses (10-100 nM) of RA for up to 6 days in the presence of a phosphate donor (beta-glycerophosphate) but in the absence of ascorbic acid. Within 4 days of treatment, RA dramatically induced expression of the alkaline phosphatase (APase), osteonectin, and osteopontin genes, caused a several-fold increase in APase activity, and provoked massive mineral formation while it left type X collagen gene expression largely unchanged. The mineral had a mean Ca/Pi molar ratio of 1.5; Fourier transform infrared spectra confirmed that it represented hydroxyapatite. Mineralization was completely abolished by treatment with parathyroid hormone; this profound effect confirmed that RA induced cell-mediated mineralization and not nonspecific precipitation. When cultures were treated with both RA and ascorbic acid, there was a slight further increase in APase activity and increased calcium accumulation. The effects of RA were also studied in cultures of immature chondrocytes isolated from the caudal portion of sternum; however, RA only had minimal effects on mineralization and gene expression in these cells. Thus, RA appears to be a rapid, potent, maturation-dependent, ascorbate-independent promoter of terminal maturation and matrix calcification in chondrocytes. PMID- 8344390 TI - Activation of the gene for atrial natriuretic factor during in vitro cardiac myogenesis by P19 embryonal carcinoma cells. AB - We examined the transcriptional activity profile of the gene for atrial natriuretic factor (ANF) in mouse embryonal carcinoma P19 cells which had been induced for in vitro cardiac myogenesis. Differentiation was assessed visually, by the degree of spontaneous beating activity, and by the appearance of striated muscle structures detected by immunofluorescence with a myosin heavy chain antibody. Northern blot analysis of RNA isolated at regular intervals throughout the differentiation program revealed abundant cardiac alpha-actin transcripts beginning at Day 6, reaching maximum levels during Days 7 to 8 and declining to low levels by Days 12 to 15. Throughout this period, the transcriptional profile of the ANF gene was similar to that of alpha-actin but at lower levels; thus, in vivo stages of abundant ANF and structural muscle gene transcription were not reached and these gene expression states appear to be uncoupled. Using the more sensitive assay of reverse transcriptase-mediated polymerase chain reactions, we observed the presence of ANF transcripts even in small samples of muscle-induced P19 cells and not in neuron-induced or undifferentiated P19 cells. Induced ANF transcript levels reached about 5-10% that found in adult atrium muscle tissue. ANF gene activity was further corroborated by nuclear transcriptional run-on assays. The P19 stem cell model system will be of value in the study of early events during cardiac muscle commitment and differentiation. PMID- 8344392 TI - Differential subcellular distribution of mortalin in mortal and immortal mouse and human fibroblasts. AB - Mortalin, p66mot-1, from the cytosolic fractions of mouse embryonic fibroblasts (MEF) has been identified. We have cloned and characterized it as a novel member of mouse hsp70 family [R. Wadhwa, S. C. Kaul, Y. Ikawa, and Y. Sugimoto (1993) J. Biol. Chem. 268, 6615-6621]. We report that immortal clones from MEF such as NIH 3T3, RS4, and Balb/c 3T3 harbor the same or a very similar protein but in the perinuclear locale. Biochemical analysis revealed that the proteins from mortal (MEF) and immortal (NIH 3T3) fibroblasts do not show gross differences. However, the phenomenon of differential distribution of p66 protein in mortal and immortal fibroblasts is conserved in three different strains of mouse and, interestingly, in human fibroblasts, too. The data suggest that at least one common step is involved in immortalization of mouse and human fibroblasts and also point to the practical implication(s) of such easily detectable differences. PMID- 8344391 TI - Retinoic acid-induced heparin-binding factor (RIHB) mRNA and protein are strongly induced in chick embryo chondrocytes treated with retinoic acid. AB - Retinoic acid-induced heparin-binding factor (RIHB) is a highly basic polypeptide expressed during early chick embryogenesis. We have examined the induction of RIHB by retinoic acid in chondrocytes isolated from the sterna of Day 15 chick embryos and the effects of exogenous RIHB on these cells. There is an induction of RIHB mRNA in chondrocytes which is dose dependent, with maximal levels of expression observed with concentrations of retinoic acid in the 10(-6) M range. RIHB mRNA is first observed 16 h after commencement of treatment, is maximal after 24-48 h, and is completely attenuated after 5 days. This transient pattern of expression is very similar to that of type X collagen; however, RIHB induction precedes that of type X collagen by about 24 h. The expression of both RIHB and type X collagen precedes the drop in keratan sulfate:chondroitin sulfate proteoglycan and type II collagen expression and the surge of fibronectin expression. The induction of RIHB mRNA is accompanied by an increased synthesis of the protein. No RIHB can be detected in untreated chondrocytes; however, large amounts are produced by cells treated with 5 x 10(-7) M retinoic acid. The protein is recovered mainly in the culture medium and bound to the extracellular matrix. Only a small amount can be detected in cell extracts. RIHB can be detected in the culture medium after 16-24 h and, unlike the mRNA, persists over the 5-day period examined. The effect of exogenous RIHB (purified from chick embryos) on chondrocyte proliferation and morphology was examined. When added to the culture medium in concentrations of up to 500 ng/ml RIHB had no effect on [3H]thymidine incorporation or cell morphology. Thus, RIHB is not the direct mediator of retinoic acid for these cells, but is strongly induced during the treatment. PMID- 8344393 TI - Influence of matricial molecules on growth and differentiation of entrapped chondrocytes. AB - Primary cultures of rabbit articular chondrocytes have been cultivated normally and within three-dimensional systems using different alginate matrices. The in vitro proliferation capacity of the cells immobilized in the calcium alginate beads was investigated. The growth curve showed that chondrocytes are able to grow and to divide for several days inside the beads; in parallel an increase in protein contents was also measured. The differentiated phenotype of rabbit articular chondrocytes consists of cartilage-specific proteoglycans. During serial monolayer cultures this phenotype was lost and replaced by a low level of proteoglycan synthesis. On the contrary when cultivated in beads, entrapped cells maintained their differentiated phenotype over time; the rates of proteoglycan were similar to those of primary chondrocytes. All these parameters were tested comparatively using different substrata in monolayer cultures and in alginate gels. Assays were carried out to assess the influence of type I collagen, type IV collagen, and of fibronectine on the growth as well as on the differentiation phenotype. The encapsulation methodology is readily applicable to the culture of chondrocytes in single beads, in multiwell dishes, or to mass culture for a bioproduction of extracellular matrix components. PMID- 8344394 TI - Reproductive life of French-Canadians in the 17-18th centuries: a search for a trade-off between early fecundity and longevity. AB - One of the predictions derived from Williams' (1957) evolutionary theory of senescence is the existence of a trade-off between early fecundity and longevity. The population register of the French immigrants to Quebec in the 17th century and of the first Canadians in the 17th and 18th centuries was used to detect such a trade-off in a noncontraceptive human population living at a time when longevity had not been prolonged by medical care and was not artificially shortened by wars, epidemics, or other external causes. No evidence for such a trade-off could be detected in these populations which had not yet reached the demographic transition phase (i.e., the historical period when longevity began to be extended and the progeny began to be reduced). Results are discussed in connection with the various studies aiming to test the Williams' theory. PMID- 8344395 TI - Fatty acid composition of adipose tissue in aged rats: effects of dietary restriction and exercise. AB - Little is known about the long-term effects of diet restriction, exercise, and aging on the fatty acid composition of adipose tissue. To investigate these effects, male Wistar rats were placed in one of four experimental groups: 1) ad libitum fed, nonexercised; 2) ad libitum fed, exercised; 3) diet restriction, nonexercised; and 4) diet restriction, exercised. Exercise consisted of swimming on alternate days, and diet-restricted animals were fed every other day. Animals were assigned to one of the four treatment groups at weaning, and the fatty acid composition in the epididymal, perirenal, and inguinal fat depots were determined every 4 months from 12 to 28 months of age. All animals were fed the same diet so the relative percentage of fatty acids in the diet did not contribute to the changes observed in adipose tissue fatty acid composition. Regardless of treatment groups and fat depot, the concentration of saturated fatty acids in adipose tissue tended to decrease as body weight increased. Saturated fatty acid composition was greater in the diet-restricted than the ad libitum-fed groups. The saturated fatty acid concentration was different between the three fat depots (perirenal 27.8%, inguinal 24.7%, and epididymal 21.6%; P < 0.001). The linoleic acid content did not change with age in the epididymal or perirenal fat depot; however, the change was significant for the inguinal fat depot. Following a large decrease in inguinal linoleic concentration through 20 months, linoleic acid concentration increased in all treatments between 20 and 28 months. The results indicate that diet restriction, exercise, and aging have significant effects on adipose tissue fatty acid composition and these effects are different depending on the anatomical location of the adipose tissue depot. PMID- 8344396 TI - Expression of protease genes in the gastric mucosa during aging. AB - The current investigation examines the changes in the expression of pepsinogen C and cathepsin D and E genes in the gastric mucosa during aging and following physiological stimuli of fasting and refeeding. Northern blot analysis of gastric mucosal RNA, isolated from overnight fasted 6-, 12-, and 24-month-old male Fischer 344 rats, revealed that although steady-state mRNA levels of each of these protease remained essentially unchanged between 6 and 12 months of age, in 24-month-old rats the levels were decreased by about 60%, when compared with their younger counterparts. Interestingly, the relative concentration of beta actin mRNA--but not 18s rRNA--in 12- and 24-month-old rats was also decreased by 23% and 37%, respectively, when compared with 6-month-old animals. In the next set of experiments, groups of young (3 month) and aged (24 month) rats were either fed throughout (controls) or fasted for 48 h and then fed for 6 h and 24 h. Gastric mucosal RNA from each group was assayed for steady-state mRNA levels of pepsinogen C and cathepsin D. Results showed that whereas in young rats fasting decreased pepsinogen C and cathepsin D mRNAs by 80-85%, in aged rats only pepsinogen mRNA was significantly decreased (45%), when compared with the corresponding initial fed controls. In both age groups, refeeding increased pepsinogen C mRNA concentration essentially to the respective initial fed levels. In contrast, cathepsin D mRNA levels in the gastric mucosa of aged rats was affected neither by fasting nor by refeeding. Our current data show that aging not only diminishes the expression of protease genes in the gastric mucosa, but also the expression of one of its structural genes, beta-actin. In addition, responsiveness of these protease genes to the physiological stimuli of fasting and refeeding is also attenuated by aging. We postulate that these age-related changes may in part be due to diminished differentiation of gastric mucosal cells. PMID- 8344397 TI - Age-associated damage in mitochondrial function in rat hearts. AB - The aim of this study is to elucidate effects of aging on mitochondrial function and mitochondrial DNA (mtDNA) in rat heart and liver. The activities of complex I and complex IV of heart mitochondria of rats aged 100 weeks decreased significantly by 31% and 22%, respectively, compared with those of rats aged 7 weeks. No significant changes were observed in these two parameters in rats aged 7 weeks and aged 55 weeks. There were no significant differences in the specific activities of complex II and complex III among the age groups of 7, 55, and 100 weeks. The mtDNA content decreased by 58% in rats aged 100 weeks compared with that in rats aged 7 weeks. Content of 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative product of deoxyguanosine (dG), increased by 130% in rats aged 100 weeks compared with that in rats aged 7 weeks. No significant changes were observed in these parameters between rats aged 7 weeks and 55 weeks. In contrast to heart mtDNA, these age-dependent changes were not observed in liver mitochondria at rats aged up to 100 weeks. From our results, age-associated decline in mitochondrial function might play an important role in cell aging, particularly in postmitotic cells such as heart muscle, and accumulation of oxidative damage to mtDNA might be involved in this mechanism. PMID- 8344398 TI - Porfiromycin as an adjunct to radiotherapy in young and old mice. AB - Radiobiological data and measurements with O2 microelectrodes show that EMT6 tumors implanted into aged mice have a higher proportion of radioresistant, hypoxic cells than do tumors implanted into young adult animals; radiation is less effective in killing cells in tumors in old mice than in tumors in young adult mice. The studies reported here examine the effects of porfiromycin (POR), a bioreductive alkylating agent shown previously to be preferentially toxic to hypoxic EMT6 cells in vitro and in solid tumors in young adult mice. POR was effective in attacking the hypoxic cells of tumors in aged mice; regimens combining POR with x-rays overcame the radioresistance of tumors in the old animals. Comparisons of the distribution of 3H-labeled POR in young and old mice showed that tumors in aged mice had a slightly larger proportion of areas with necrotic features, which bound higher levels of tritiated POR than did healthy tumor regions without necrotic features. Studies of histology, lissamine green distributions, binding of tritiated POR, and radiation and POR cytotoxicity suggested that tumors in old mice contained a larger proportion of poorly perfused tumor cells, and that cells in these regions were resistant to radiation and sensitive to POR. Studies of the distribution of POR in normal tissues and of the toxicity of POR to bone marrow progenitor cells (CFU-GM) revealed no differences between young and old animals, showing that the differences observed in tumors reflected differences in the microenvironments within the tumors, rather than differences in the processing of drug in young and old animals. PMID- 8344399 TI - Leishmania pifanoi: kinetics of messenger RNA expression during amastigote to promastigote transformation in vitro. AB - Conditions have been developed which induce axenically grown Leishmania pifanoi amastigotes to transform into the promastigote stage in a highly reproducible fashion. Transformation was induced by a temperature shift from 31 to 22 degrees C, was inhibited by high cell concentration (> or = 40 x 10(6) cells/ml), and was unaffected by pH from 5.5-7.2. Morphologic transformation was first evident at 8 hr after induction, had occurred in > 50% of cells by 24 hr, and was > 90% complete by 48 hr. This system enabled study of the kinetics of mRNA expression during the transformation of Leishmania. The differentially expressed mRNAs for ATPase 1a and 1b, alpha- and beta-tubulin, P100/11E, Pro-1, and pLm 2, 7, 14, and 16 exhibited complex patterns of temporal expression, suggesting a highly regulated process. Differentiation on the biochemical level was evident within an hour and continued throughout the course of morphologic transformation. In addition, transformed L. pifanoi promastigotes in the plateau growth phase expressed genes characteristic of metacyclic promastigotes. Axenically cultured L. pifanoi should provide an excellent model for the study of differentiation in Leishmania. PMID- 8344400 TI - Plasmodium berghei: is nitric oxide involved in the pathogenesis of mouse cerebral malaria? AB - To analyze whether nitric oxide may be involved in the pathogenesis of the mouse cerebral malaria (CM), nitrate and nitrite were first measured in urines of Plasmodium species infected mice. The CM-susceptible CBA/J mice were infected with either Plasmodium berghei or Plasmodium chabaudi, and the CM-resistant BALB/c mice were infected with P. berghei. No increased levels of nitrate and nitrite were detected in urine of mice infected with Plasmodium whatever the time of monitoring. In contrast, the nitrite level was found to be increased in the urine of C3H/HeJ mice infected with Trypanosoma cruzi, used as a positive control for nitrate excretion in urine. Two analogs of L-arginine, the L-NG-monomethyl arginine acetate hydrate (L-NMMA) and N omega-nitro-L-arginine, which inhibit the nitric oxide synthase were used. CBA/J mice infected with P. berghei and treated ip with the analogs developed full neurological symptoms. Even administered intracranially, L-NMMA did not reverse CM. The role of nitric oxide in the CM pathogenesis of the mouse model is discussed. PMID- 8344401 TI - Entamoeba histolytica: the EHZc3 cDNA clone encodes a zinc-binding protein. PMID- 8344402 TI - Plasmodium: control of gene expression in malaria parasites. PMID- 8344403 TI - Toxoplasma gondii: differential location of antigens secreted from encysted bradyzoites. AB - Since we have previously demonstrated the protective role against infection played by Toxoplasma excreted-secreted antigens (Darcy et al. Parasite Immunology, 10, 553-567, 1988), the aim of the present work was an attempt to precisely define the location of GRA1, GRA2, and GRA5 in both the tachyzoite and the bradyzoite stages from distinct strains, in order to explore the mechanisms of secretion by Toxoplasma gondii. Three monoclonal antibodies (Charif et al. 1990) and colloidal immunogold labeling were used to localize the 27-, 28.5-, and 21-kDa target antigens to the matrix of the dense granules of tachyzoites and bradyzoites. They were, moreover, detected in the parasitophorous vacuole and in the cyst ground substance after host cell invasion. Our data suggest that a selective sorting mechanism for dense-granule contents exists at least in encysted bradyzoites. GRA2 was found preferentially associated with the ground substance of the cyst wall and the tubular elements of the network of the modified host cell phagosome, whereas GRA5 was located on the delimiting membrane of both the cyst wall and the parasitophorous vacuole. These observations reveal the selective targeting of dense-granule molecules, which could have different functions and fates when exocytosed into the parasite-containing vacuole. PMID- 8344405 TI - Ductular proliferation and hepatic secretory function in experimental fascioliasis. AB - Proliferation of bile duct-like epithelial cells is a common feature of extrahepatic biliary obstruction and it is also present in other forms of liver disease. Experimental infestation with Fasciola hepatica induces hyperplasia of ductular cells together with different functional alterations, such as hypercholeresis, in the rat. We have investigated the contribution of ductular biliary secretion to the hypercholeretic phenomenon in rats with experimental fascioliasis. Infestation was induced by oral administration of 20 metacercariae of F. hepatica. Twelve weeks later, histological study of the liver showed a hyperplastic reaction with proliferation of bile duct-like structures. Basal bile flow in infested animals was significantly higher than that of control animals (+17%), while biliary secretion of bile acids did not significantly differ between both groups. Bile flow increase was associated in parasitized animals with a significantly lower [14C]mannitol bile:plasma ratio (-23%). Intravenous secretin administration (0.3 CU/100 g body wt min) induced a significant increase in the biliary concentration of bicarbonate (+21%) and an enhancement of bile flow (+21%) only in the animals with ductular proliferation. Taurocholate infusion (0.5 nmol/100 g body wt min) produced a similar bile flow increase both in control rats and in rats with proliferated biliary ductules. These results indicate that proliferated bile ductules and ducts spontaneously secrete bile in response to infestation by F. hepatica and that secretin-stimulated bile flow originates at the proliferated biliary structures. PMID- 8344404 TI - Trichinella spiralis: genetic basis and kinetics of the anti-encysted muscle larval response in miniature swine. AB - Primary-infected swine lymphocyte antigen (SLA) inbred miniature swine, NIH minipigs, of the SLAa/a haplotype (aa) display markedly reduced Trichinella spiralis-encysted muscle larval (ML) burdens 6 weeks after homologous challenge and are therefore referred to as responders against encysted T. spiralis ML. To investigate the kinetics and genetics of the anti-encysted ML response, and in an attempt to ascertain the mechanisms underlying this phenomenon, NIH minipigs of multiple SLA haplotypes, designated either as ax (aa, ac, ad, af, ag, dh and hh) or non-ax (cc, cd, and dd), received a primary inoculation of 300 T. spiralis ML followed by a challenge inoculation of 10,000 ML 6 or 17 weeks later. Pigs were examined at necropsy and at Weeks 1, 2, 3.5, and 6 after challenge. Statistical cluster analyses, based on final ML burdens, performed on 129 pigs in 13 trials, revealed that 47% of primary-plus-challenged ax pigs exhibited responder phenotype as early as 1-2 weeks after T. spiralis challenge whereas this response was manifested in only 8% of non-ax pigs. No correlation was observed between responder phenotype and T. spiralis-specific blastogenesis, cell expression of class I or class II SLA molecules, lymphoid cell subsets, adult worm numbers, or fecundity. Although some ax responder pigs exhibited a localized inflammatory response with a prominent eosinophilic infiltrate surrounding degenerating encysted ML, no correlation was observed between responder phenotype and either peripheral blood eosinophilia or the ability of eosinophil-enriched cell populations from responder pigs to adhere to or destroy encysted ML in vitro. PMID- 8344406 TI - Theileria parva: detection of genomic polymorphisms by polymerase chain reaction amplification of DNA using arbitrary primers. AB - Genomic DNA fingerprints were generated from Theileria parva piroplasm DNA by polymerase chain reaction amplification using arbitrary decamers as primers. Four of 12 primers tested generated amplified fragments which were polymorphic between different T. parva stocks or clones. Hybridization of radiolabeled total amplification products to Southern blots of T. parva piroplasm and uninfected bovine DNA confirmed that none of the amplified fragments were derived from any contaminating bovine DNA which may have been present in small quantities. Polymorphic DNA fragments were reproducibly amplified from independent DNA preparations made from cloned parasites. Individual amplified DNA fragments were gel purified and shown to hybridize to size-polymorphic EcoRI fragments in T. parva genomic DNA. Hybridization of individual amplified fragments to total fingerprints, generated using the same arbitrary primer, demonstrated that a single primer detected at least three independent genomic polymorphisms in T. parva DNA. PMID- 8344407 TI - Leishmania mexicana: proteinase activities and megasomes in axenically cultivated amastigote-like forms. AB - Proteinase activities and megasomes were examined in axenically cultivated amastigote-like forms, freshly isolated lesion amastigotes, and promastigotes. Megasomes were absent in promastigotes and present in both amastigote stages, but they seemed to be less numerous and more homogeneous in cultured amastigote-like forms. Contrasting with the poor detection of proteinase activities in promastigote lysates, both types of amastigotes shared multiple proteinases, which were classified in two groups: (a) 60 to > 100 kDa, o-phenanthroline sensitive activities; and (b) 23- to 40-kDa cysteine proteinases, of which those resolving as 35- to 40-kDa bands in gelatin gels were more clearly visualized in lysates of cultured amastigote-like forms. Incubation of both kinds of amastigotes with 0.25 to 1.0 microM of either Z-Phe-AlaCHN2 or Z-Tyr-AlaCHN2 selectively inactivated cysteine proteinases, but not the 35- to 40-kDa activities, which, again, were detected with higher intensity in cultured amastigote-like forms. The expression of the 35- to 40-kDa proteinases progressively increased when promastigotes were allowed to transform into amastigote-like forms or when lesion amastigotes were incubated at 34 degrees C for different time periods prior to exposure to Z-Phe-AlaCHN2; activities comparable to those of amastigote-like forms were attained within 24 to 48 hr. The activities resistant to Z-Phe-AlaCHN2 in vivo were fully inhibited by E-64 or Z-Phe-AlaCHN2 during gelatin digestion, suggesting that the 35- to 40-kDa proteinases were mainly inactive before cell lysis. The presence of cycloheximide (at 10, 50, and 100 micrograms/ml) during the pulse with Z-Phe-AlaCHN2 abolished the 35- to 40-kDa activities of lesion amastigotes and significantly reduced gelatin digestion by the similar enzymes of cultured amastigote-like forms. In the latter, the 35- to 40-kDa proteinases were no more detected when cycloheximide was given 60 min prior to Z-Phe-AlaCHN2. The results indicate higher rates of synthesis of the 35- to 40-kDa enzymes, and the existence of a more representative pool of inactive enzyme precursors, in cultured amastigote like forms. PMID- 8344408 TI - Gametocytogenesis induction by Berenil in cultured Plasmodium falciparum. AB - Berenil, which is known to inhibit synthesis of nucleic acid, DNA and RNA, and polyamine, induced gametocytogenesis in cultured Plasmodium falciparum, although the mechanism by which Berenil induces gametocytogenesis is unknown. Asexual parasites of a strain of P. falciparum that seldom produce gametocytes in in vitro culture began gametocytogenesis after 2-24 hr treatment with RPMI 1640 medium containing Berenil (final concentration, 0.1-10.0 micrograms/ml) with horse serum. Gametocytogenesis was consistently observed from 3 days after the addition of Berenil to culture. After parasites were cultivated in RPMI 1640 medium containing Berenil (final concentration, 3.0-10.0 micrograms/ml) and concanavalin A with horse serum for 2 hr, Berenil and concanavalin A were removed from culture medium by centrifugation. Nevertheless, induction of gametocytogenesis was observed. The addition of concanavalin A (final concentration, 10 micrograms/ml) to RPMI 1640 medium containing Berenil enhanced the induction of gametocytogenesis by Berenil. However, when RPMI 1640 medium with concanavalin A was used without the addition of Berenil, no gametocytogenesis was observed as in RPMI 1640 medium alone. PMID- 8344409 TI - Plasmodium falciparum: analysis of the cytoadherence inhibition of the human monoclonal antibody 33G2 and of antibodies reactive with antigen Pf332. AB - The capacity of a human monoclonal antibody (MAb 33G2) to interfere in vitro both with Plasmodium falciparum merozoite invasion and cytoadherence of infected erythrocytes to melanoma cells has been reported. MAb 33G2 cross-reacts with several P. falciparum antigens but shows highest reactivity with repeated sequences in the asexual blood stage antigen Pf332. This study was conducted in order to further analyze the cytoadherence inhibition mediated by MAb 33G2 and to evaluate the relative contribution of antibodies to Pf332 in the inhibitory activity of immunoglobulins from P. falciparum immune donors. We show here that MAb 33G2 inhibits cytoadherence of infected erythrocytes (PRBCs) with similar efficiency independently of the strain of parasite, while the inhibitory capacity of immunoglobulin fractions from Liberian immune donors was restricted to some strains only. There appears to be no correlation between the reactivity with Pf332 of immunoglobulin preparations from different donors and their capacity to inhibit cytoadherence of PRBCs to melanoma cells. In contrast to MAb 33G2, polyclonal antibodies affinity purified on the Pf332 peptide containing the epitope seen by the MAb showed little or no inhibition of cytoadherence of infected erythrocytes. PMID- 8344410 TI - Haemonchus contortus: ivermectin-induced paralysis of the pharynx. AB - How the avermectins cause the elimination of gastrointestinal nematodes from host animals has not yet been clearly identified. Using visual and radiometric parameters to measure oral ingestion in Haemonchus contortus, we showed that ivermectin (IVM) rapidly inhibited ingestion at concentrations > or = 10(-10) M. Motility, monitored quantitatively with an automated motility meter, was unaffected by IVM at concentrations < or = 10(-8) M, while ATP levels were unaffected at concentrations < or = 10(-6) M. Since motility and ATP levels, independent measures of short-term viability, are unaffected by concentrations of IVM that effectively block oral ingestion, the drug can be used as a chemical ligature. Although H. contortus was shown to be dependent upon an exogenous supply of glucose for survival in culture, IVM (10(-9) and 10(-7) M) altered neither the uptake of 3-O-[3H]methylglucose nor the metabolism of [13C]glucose by the parasite. These data suggest that H. contortus depends upon the transcuticular uptake of glucose in culture. If oral ingestion of other nutrients is essential for long-term survival in vivo, disruption of this process may represent the primary mechanism of IVM action. PMID- 8344411 TI - Babesia bovis: characterization of the T helper cell response against the 42-kDa merozoite surface antigen (MSA-1) in cattle. AB - The Babesia bovis major merozoite surface antigen (MSA-1) is a 42-kDa integral membrane glycoprotein previously shown to induce immunodominant antibody responses in cattle protectively immune to B. bovis and to induce neutralizing antibody. Recent studies have also shown that MSA-1 B cell epitopes common to New World strains of B. bovis are not present in either Israel or Australia strains. To understand the potential role of this protein in protective immunity, T helper cell responses specific for MSA-1 were characterized in Babesia-immune cattle. Peripheral blood mononuclear cells from immune cattle proliferated against affinity-purified recombinant MSA-1 protein expressed in Escherichia coli. MSA-1 preferentially stimulated the growth of CD4+ T cells in cell lines cultured with antigen for 4 weeks. MSA-1-reactive cell lines responded to a membrane fraction of B. bovis merozoites, suggesting recognition of the native protein. However, B. bovis-reactive T cell lines and T helper clones established by stimulation with crude parasite membrane antigen failed to respond to recombinant MSA-1, indicating that this antigen is not immunodominant for T cells. The majority of MSA-1-specific T helper clones reacted to unfractionated merozoite membrane antigen from New World B. bovis strains, but none of the clones responded to Australia B. bovis or to a Mexico strain of Babesia bigemina. Several T helper clones produced low levels of cytokines when stimulated with concanavalin A and interleukin-2. Northern blot analysis revealed the expression of interleukin-2, interleukin-4, interferon-gamma, and tumor necrosis factor-alpha messenger RNA in mitogen-stimulated T helper clones, showing that the clones examined expressed an unrestricted T helper phenotype. We conclude that the MSA-1 protein, although serologically immunodominant and capable of inducing neutralizing antibodies as well as a T helper cell response, is not an immunodominant T cell antigen. Furthermore, the parasite strain specificity of the Th clones supports previous findings of extensive polymorphism in the MSA-1 glycoprotein and suggests that like B cell epitopes, T cell epitopes reside in a nonconserved portion of the protein. PMID- 8344412 TI - Biochemical events in naturally occurring forms of cell death. AB - Several molecular elements of programmed cell death and apoptosis have recently been revealed. The function of gene products which deliver the lethal 'hit' is still not known. Well-characterized and newly discovered cell surface structures (e.g. antigen receptors, FAS/APO-1), as well as transcriptional factors (steroid receptor, c-myc, P53, retinoblastoma protein and others), have been implicated in the initiation of the death pathway. Negative regulators of the process (ced-9 gene product in programmed death of cells in Caenorhabditis elegans and bcl-2 protein in apoptosis) have been described. Biochemical mechanisms responsible for the silent nature of natural deaths of cells include their rapid engulfment (mainly through integrin receptors), transglutaminase-catalyzed cross-linking of cellular proteins, and fragmentation of DNA. Several lines of evidence suggest that distinct molecular mechanisms may operate in various forms of natural cell death. PMID- 8344413 TI - The specificity of the S1' subsite of cysteine proteases. AB - The specificity of the S1' subsite of the cysteine proteases cathepsin B, L, S and papain has been investigated using a series of intramolecularly quenched fluorogenic substrates (Dansyl-Phe-Arg-AA-Trp-Ala) where the P1' amino acid (AA) has been varied. Taken individually, each enzyme displays a relatively broad S1' subsite specificity and this subsite cannot be considered as a primary site of specificity. Notable differences do exist however between the various proteases. Cathepsin B prefers large hydrophobic residues in the P1' position of a substrate while cathepsin L has an opposite trend, favoring amino acids with small (Ala, Ser) or long but non-branched (Asn, Gln, Lys) side chains. Cathepsin S and papain display a somewhat broader S1' subsite specificity. PMID- 8344414 TI - Determination of a functional lysine residue of a plant cysteine synthase by site directed mutagenesis, and the molecular evolutionary implications. AB - Comparison of seven deduced amino acid sequences of cysteine synthase (O-acetyl-L serine (thiol)-lyase, EC 4.2.99.8) from plants and bacteria disclosed the presence of 12 conserved Lys residues, which can be candidates for a functional binding site for pyridoxal phosphate cofactor. These 12 conserved Lys residues in a cDNA clone encoding spinach cysteine synthase A were replaced with Gly by oligonucleotide-directed in vitro mutagenesis. These Lys-->Gly mutated cDNAs were transferred into Escherichia coli NK3, a cysteine auxotroph lacking both cysteine synthase loci, cysK and cysM. One mutant replaced at Lys-49 could not complement the cysteine requirement of NK3, whereas other mutants and wild-type clone could. No enzymatic activity of cysteine synthase A was detected either in the cell-free extracts of E. coli NK3 transformed with the Lys-49 mutant. These results indicated that Lys-49 is a functional residue for the catalytic activity of cysteine synthase. This Lys residue is conserved in other evolutionarily related amino acid-metabolizing enzymes catalyzing reactions involving the beta-carbon of amino acids. PMID- 8344415 TI - Site-directed mutagenesis of the tick-borne encephalitis virus NS3 gene reveals the putative serine protease domain of the NS3 protein. AB - Several mutations were introduced into the putative serine protease domain of the tick-borne encephalitis virus NS3 protein and into a possible internal cleavage site within the protein. The influence of these mutations on proteolytic activity of NS3 protein and NS3' protein formation was tested in vitro. It was found that NS3' formation was not dependent on the activity of the NS3 N-terminal serine protease. Mutations affecting the Ser-138 residue of the NS3 protein prohibited cleavage between NS2B and NS3 proteins when the NS2B-NS3 part of the viral genome was expressed in vitro, suggesting the key role of Ser-138 in viral serine protease functioning. PMID- 8344416 TI - Zonation of glucokinase in rat liver changes during postnatal development. AB - In the liver many metabolic pathways are preferentially localized in different zones of the acinus. It is assumed that this zonation allows an efficient adaptation to different states of nutrition, because alternative pathways can be regulated independently. It is reported that the rate limiting enzyme for the glycolytic pathway, glucokinase (EC 2.7.1.2), is predominantly located in the pericentral zone. The gene expression of glucokinase is induced to a maximum level after a carbohydrate-rich diet. In starved or diabetic rats glucokinase gene expression is barely detectable. In postnatal development glucokinase is induced to significant levels only from day 14 onwards. The distribution of the glucokinase protein in the rat liver lobule in the first 4 weeks of postnatal life was investigated by immunohistochemistry and compared to the distribution observed in adult rats. In adult rats considerably high levels of glucokinase are measureable as shown by immunoblotting utilizing a monospecific antibody and a photometric assay of glucokinase enzyme activity, respectively. Immunohistochemically the hepatic glucokinase protein is detected in the perivenous area. During postnatal development, the quantities of hepatic glucokinase protein and glucokinase enzyme activity start to increase significantly from day 15 onwards. Subsequently, glucokinase levels rise further until day 29. In contrast to the results obtained by immunoblotting, glucokinase is already detectable in some liver cells in sections from 6-day-old rats by immunohistochemistry. The liver lobule structure at this age is not completely developed, therefore it is not possible to definitely assign these cells to periportal or pericentral areas. At day 10 post partum the number of glucokinase expressing cells, which appear to be localized preferentially in the periportal zone, increases. In agreement with the immunoblotting, an immense increase in glucokinase activity was observed at day 14. The periportal zonation, clearly detectable at this time, remains stable until day 24. In sections from 29-day-old rats the periportal zonation begins to change into a more homogeneous pattern with a slight preference for periportal areas. The observed appearance of the periportal zonation of glucokinase during neonatal development is obviously in contrast to the perivenous expression of glucokinase in adult rats. PMID- 8344417 TI - Mutation-spectrum of a true abasic site in codon 12 of a c-Ha-ras gene in mammalian cells. AB - An abasic site is postulated to be a premutagenic lesion. We previously reported that a c-Ha-ras gene with an abasic site analogue at either the first or the second position of codon 12 induced the formation of foci by point-mutational activation of the gene [Kamiya et al. (1992) Nucleic Acids Res. 20, 4409-4415]. In this study we constructed c-Ha-ras genes with a true abasic site in codon 12. The ras genes were found to be activated in NIH3T3 cells by a mutation to A at the modified and flanking positions, and the flanking mutations were detected more frequently. PMID- 8344419 TI - Cloning and functional expression in Escherichia coli of a cyanobacterial gene for lycopene cyclase, the enzyme that catalyzes the biosynthesis of beta carotene. AB - Carotenoids with cyclic end groups are essential components of the photosynthetic membrane in all known oxygenic photosynthetic organisms. These yellow pigments serve the vital role of protecting against potentially lethal photo-oxidative damage. Many of the enzymes and genes of the carotenoid biosynthetic pathway in cyanobacteria, algae and plants remain to be isolated or identified. We have cloned a cyanobacterial gene encoding lycopene cyclase, an enzyme that converts the acyclic carotenoid lycopene to the bicyclic molecule beta-carotene. The gene was identified through the use of an experimental herbicide, 2-(4 methylphenoxy)triethylamine hydrochloride (MPTA), that prevents the cyclization of lycopene in plants and cyanobacteria. Chemically-induced mutants of the cyanobacterium Synechococcus sp. PCC7942 were selected for resistance to MPTA, and a mutation responsible for this resistance was mapped to a genomic DNA region of 200 bp by genetic complementation of the resistance in wild-type cells. A 1.5 kb genomic DNA fragment containing this MPTA-resistance mutation was expressed in a lycopene-accumulating strain of Escherichia coli. The conversion of lycopene to beta-carotene in these cells demonstrated that this fragment encodes the enzyme lycopene cyclase. The results indicate that a single gene product, designated lcy, catalyzes both of the cyclization reactions that are required to produce beta-carotene from lycopene, and prove that this enzyme is a target site of the herbicide MPTA. The cloned cyanobacterial lcy gene hybridized well with genomic DNA from eukaryotic algae, thus it will enable the identification and cloning of homologous genes for lycopene cyclase in algae and plants. PMID- 8344418 TI - Detection of complex gangliosides in human amniotic fluid. AB - Gangliosides are possibly very potent immunosuppressive molecules. Here we show that human amniotic fluid contains high concentrations of a number of previously unnoted, structurally complex and highly polar gangliosides. These unusual molecules are present early in pregnancy (first trimester), increase in concentration with gestational age, and reach maximum levels (0.8 microM) at term. Since similar gangliosides have been detected in human placenta, trophoblast, and amnion, we suggest that these molecules are shed into the amniotic fluid bathing these tissues. PMID- 8344421 TI - The structure of the complex between avidin and the dye, 2-(4'-hydroxyazobenzene) benzoic acid (HABA). AB - The crystal structure of the complex formed between the egg-white biotin-binding protein, avidin, and the dye, 2-(4'-hydroxyazobenzene) benzoic acid (HABA), was determined to a resolution of 2.5 A. The interaction of avidin with the benzoate ring of HABA is essentially identical to that of the complex formed between HABA and streptavidin (the bacterial analogue of the egg-white protein). This interaction emulates the definitive high-affinity interaction of both proteins with the ureido moiety of biotin. The major difference between the avidin- and streptavidin-HABA complexes lies in their interaction with the hydroxyphenyl ring of the dye molecule; in avidin, two adjacent amino acid residues (Phe72 and Ser73), which are not present in streptavidin, form additional interactions with this ring. These are suggested to account for the higher affinity of avidin for HABA. The characteristic red shift, which accompanies the interaction of both proteins with the dye, was traced to a proposed charge-transfer complex formed between the hydroxyphenyl ring of HABA and the indole ring of Trp70 in avidin (Trp79 in streptavidin). Comparison of binding site residues of two such similar proteins versus their markedly different affinities for two such different substrates should eventually contribute to a better design of biomimetic reagents and drugs. PMID- 8344420 TI - Molecular cloning and developmental expression of human cardiac troponin T. AB - We have isolated a full-size cDNA coding for cardiac troponin T (cTnT) from a human adult heart library, using a slow skeletal TnT probe. This cDNA detected a 1.2 kb mRNA in fetal and post-natal human heart, the amount of which increased during ontogenic development. Interestingly, a similar transcript was coexpressed in fetal skeletal muscle, together with the 0.9 kb slow skeletal muscle mRNA, and its expression was down-regulated during further development. PMID- 8344422 TI - Purification of the beta product encoded by the Streptococcus pyogenes plasmid pSM19035. A putative DNA recombinase required to resolve plasmid oligomers. AB - Genetic evidence suggests that the gene beta product of Streptococcus pyogenes plasmid pSM19035 is required for converting plasmid multimers into monomers. The beta protein was purified from cells overexpressing the cloned gene. N-terminal protein sequence analysis demonstrated that the purified protein had the predicted sequence, except that the N-terminal initiator methionine was not present. Native beta protein consists of a dimer of two identical subunits with a molecular mass of 23.8 kDa (25 kDa in SDS-PAGE). The beta protein (isoelectric point of 9.7) binds specifically to a DNA fragment (312 bp in length) which contains the promoter region of the orf alpha-gene beta operon and two regions (sites I and II) that show dyad axes of symmetry. It is proposed that protein beta binds to sites I and II to mediate resolution of plasmid oligomers. PMID- 8344423 TI - Spleen-derived growth factor, SDGF-3, is identified as keratinocyte growth factor (KGF). AB - A heparin-binding mitogen rat for rat hepatocytes was partially purified from bovine spleen by a combination of heparin-affinity, cation-exchange and gel filtration chromatography. Besides stimulating rat hepatocytes, this factor, which was designated spleen-derived growth factor-3 (SDGF-3), exhibited mitogenic activity for mouse epidermal keratinocytes but not mouse fibroblasts. Its apparent epithelial specificity and heparin-binding properties corresponded to those of keratinocyte growth factor (KGF). These findings, together with the fact that the mitogenic activity of SDGF-3 was abolished by a neutralizing monoclonal antibody specific for KGF, identify this bovine spleen-derived hepatocyte mitogen as KGF. PMID- 8344424 TI - Metal as a novel type of the enzyme substrate. Metallic cadmium photogenerated in the system CdS-formate as a substrate of the NAD-dependent hydrogenase. AB - The process of NAD+ photoreduction under the coupled action of CdS semiconductor and NAD-dependent hydrogenase from hydrogen-oxidizing bacterium Alcaligenes eutrophus may be divided into light and dark stages. At the first stage, illumination of the system leads to the photooxidation of the sacrificial electron donor and results in the reduction of the semiconductor surface. At the second dark stage NAD+ is reduced to NADH in the presence of hydrogenase. Atoms of metallic Cd(0) are shown to be the true substrate of the enzymatic reaction. The prerequisite for the electron transfer from Cd(0) to hydrogenase is enzyme adsorption on the semiconductor surface. The redox center of the hydrogenase reacting with Cd(0) atoms resides on the flavin-containing heterodimer of the protein. The activity of the hydrogenase immobilized on CdS in the reaction of NAD+ reduction by metallic Cd is close to the enzyme activity with the physiological substrates in solution. Thus, the first example of a metal being the substrate of the enzymatic process is presented. PMID- 8344425 TI - Nucleotide/H(+)-dependent change in Mg2+ affinity at the ATPase inhibitory site of the mitochondrial F1-F0 ATP synthase. AB - The interactions between ADP and Mg2+ that result in the slowly reversible inhibition of the mitochondrial F1-F0 ATPase were studied. The Ki for the inhibitory Mg2+ is shown to be strongly dependent on the occupation of the nucleotide-binding sites. The inhibitory binding site for Mg2+ is not seen unless a stoichiometric amount of ADP is added [Biochem. J. 276 (1991) 149-156]; it appears (Ki = 2.10(-6) M) in the presence of stoichiometric ADP and the affinity for inhibitory Mg2+ decreases to a Ki value of 7.10(-5) M when the second nucleotide binding site with Kd = 5.10(-6) M is loaded with ADP. The binding of the inhibitory Mg2+ is competitively inhibited by H+ ions within the pH interval 6.8-8.2. The nucleotide-dependent affinity transition of the Mg(2+)-specific site suggests that H+/Mg2+ exchange may play an important role in the catalytic mechanism of ATP synthesis/hydrolysis at the active site(s) of F1-F0 ATP synthase. PMID- 8344426 TI - Dp71, the nonmuscle product of the Duchenne muscular dystrophy gene is associated with the cell membrane. AB - The 70.8 kDa protein, Dp71, is the major Duchenne muscular dystrophy (DMD) gene product in many nonmuscle tissues including the brain. Dp71 shares most of the C terminal and cysteine-rich domains with the dystrophins but lacks the entire large rod shaped domain of spectrin-like repeats, and the N-terminal actin binding domain. The function of Dp71 is unknown. Using subcellular fractionation and immunostaining we show that Dp71 is associated with the plasma membrane. Dp71 is also associated with the plasma membrane in mdx myogenic cells transfected with a vector expressing Dp71. PMID- 8344427 TI - PDI and glutathione-mediated reduction of the glutathionylated variant of human lysozyme. AB - A mutant human lysozyme, designated as C77A-a, in which glutathione is bound to Cys95, has been shown to mimic an intermediate in the formation of a disulfide bond during folding of human (h)-lysozyme. Protein disulfide isomerase (PDI), which is believed to catalyze disulfide bond formation and associated protein folding in the endoplasmic reticulum, attacked the glutathionylated h-lysozyme C77A-a to dissociate the glutathione molecule. Structural analyses showed that the protein is folded and that the structure around the disulfide bond, buried in a hydrophobic core, between the protein and the bound glutathione is fairly rigid. Thioredoxin, which has higher reducing activity of protein disulfides than PDI, catalyzed the reduction with lower efficiency. These results strongly suggest that PDI can catalyze the disulfide formation in intermediates with compact structure like the native states in the later step of in vivo protein folding. PMID- 8344428 TI - Osteoblast-like cells have a variable mixed population of purino/nucleotide receptors. AB - Osteoblast-like UMR 106.06 cells respond to extracellular application of nucleotides with a fast intracellular calcium pulse (latency of about 20 s, half width of about 10 s), as measured with fluo-3 on a confocal laser scanning system. Cross-inhibition experiments at 50 microM show that, on a cell population basis, adenosine triphosphate (ATP) strongly inhibits the effect of uridine triphosphate (UTP) or 2-methylthio-ATP (2-MeSATP) applied within 2 min after the end of the ATP-induced pulse, while prior application of UTP or 2-MeSATP only weakly inhibits the ATP effect, and UTP and 2-MeSATP weakly inhibit each other. Furthermore, there are clear differences in cross-inhibition between individual cells. Our measurements provide strong evidence that these cells have at least two types of purino/nucleotide receptors, probably P2y and P2u, with a proportion that varies between individual cells. PMID- 8344429 TI - In vitro phosphorylation of purified tobacco-leaf phosphoenolpyruvate carboxylase. AB - C3-leaf phosphoenolpyruvate (PEP) carboxylase (PEPC) was purified about 1,000 fold from tobacco and displayed a final specific activity of 35 mumol/min/mg protein, an apparent Km (total PEP) of 95 muM [corrected] (both at pH 8.0, 30 degrees C), and an I50(L-malate) value of 0.14 mM at pH 7.3, 0.2 mM PEP. The rapid, 5-step protocol involved polyethylene glycol fractionation and sequential FPLC on hydroxylapatite, phenyl-Sepharose, Mono Q and Superose 12. The electrophoretically pure protein and purified C4-leaf PEPC were phosphorylated in vitro in a reconstituted system with PEPC-kinase isolated from illuminated tobacco and maize leaves. These reciprocal phosphorylation experiments (i) indicate that Ser11 of tobacco PEPC is the likely target residue, situated in the plant-invariant Glu/Asp-Lys/Arg-X-X-Ser phosphorylation motif near the N terminus, and (ii) lend support to the recent hypothesis that C3-leaf PEPC is subject to regulatory phosphorylation in vivo. PMID- 8344430 TI - Proteolytic processing of the hepatocyte growth factor/scatter factor receptor by furin. AB - The hepatocyte growth factor/scatter factor (HGF/SF) receptor consists of an alpha- and a beta-subunit, which are derived from a single-chain precursor by endoproteolytic processing. The precursor is not proteolytically processed in LoVo colon carcinoma cells. The uncleaved receptor immunopurified from the cells was cleaved in vitro by furin. Furthermore, the HGF/SF receptor was proteolytically processed in LoVo cells transfected with furin cDNA. These results indicate that furin is a processing endoprotease for the HGF/SF receptor. Tyrosine autophosphorylation of the uncleaved receptor was induced by HGF/SF, and the growth of the cells expressing the uncleaved receptor was stimulated by HGF/SF, indicating that the proteolytic processing of the receptor is not essential for the signal transduction of HGF/SF. PMID- 8344431 TI - Expression of heterologous phosphofructokinase genes in yeast. AB - Genes encoding phosphofructokinases (PFK) from Escherichia coli and from the human muscle were expressed in PFK-deficient strains of Saccharomyces cerevisiae under the control of an inducible GAL1 promoter. They restored PFK activity under inducing conditions and complemented the galactose-negative growth phenotype of the recipient strains. The PFK enzymes expressed appear to be stable in yeast. The human muscle enzyme crossreacts with specific antibodies and shows the expected subunit size. As expected, its activity can be activated by fructose-2,6 bisphosphate, in contrast to the bacterial enzyme. PMID- 8344432 TI - A putative transcription factor binding to the upstream region of the puf operon in Rhodobacter sphaeroides. AB - Gel shift assays of the upstream region of the puf operon in Rhodobacter sphaeroides were performed using cell-free extracts from cells grown under various culture conditions. The results suggested that a protein binding to the upstream region functioned as a repressor-like substance of the expression of the operon by oxygen tension or light. The density of the shifted band of cell-free extracts from cells irradiated with blue light under semi-aerobic conditions was higher than that with red light. Phosphatase treatment of the cell-free extracts strongly increased the DNA-binding affinity of the protein. PMID- 8344433 TI - Evidence for stacking interactions between 5-mercurated polyuridylic acid and HIV 1 p7 nucleocapsid protein obtained by phosphorescence and optically detected magnetic resonance (ODMR). AB - The photoexcited triplet state of Trp-37 in the C-terminal zinc finger of the HIV 1 p7 nucleocapsid protein was used as a probe of p7 interactions with the heavy atom-derivatized RNA homopolymer, poly-5-mercuriuridylic acid (5-HgU). Binding of p7 to 5-HgU (Hg blocked with 2-mercaptoethanol) produces an external heavy atom effect (HAE) on Trp-37 characterized by fluorescence quenching, reduction of the phosphorescence lifetime by three orders of magnitude, and the appearance of the D+E phosphorescence-detected ODMR signal, absent in unperturbed Trp, but induced by a HAE. The details of the HAE are consistent with out-of-plane van der Waals contact of Hg with the indole chromophore of Trp-37. Steric requirements suggest further that the Trp-RNA contact occurs via an aromatic stacking interaction. PMID- 8344435 TI - The 100 kDa F-actin capping protein of Dictyostelium amoebae is a villin prototype ('protovillin'). AB - The 100 kDa actin-binding protein from Dictyostelium amoebae is an F-actin capping protein that displays neither severing nor crosslinking nor nucleating activities [Hofmann et al. (1992) Cell Motil. Cytoskel. 23,133-144]. Cloning and sequencing of the gene revealed that the protein is highly homologous to vertebrate villin, a unique component of brush border microvilli and contains six domains fused to a villin-like headpiece domain via a threonine/proline rich neck region. The functional differences and similarities between the 100 kDa protein and villin are reflected in the amino acid sequences. We draw from the data the following conclusions. (i) The presence of a six domain protein in Dictyostelium suggests that in contrast to the current view gene duplications must have happened before Dictyostelium branched off during evolution. (ii) The villin-like molecule in Dictyostelium appears to be a premature villin ('protovillin') which is able to cap actin filaments but still lacks the other villin-type actin binding activities. This renders capping of actin filaments as the evolutionarily oldest function of an F-actin binding protein. PMID- 8344434 TI - 13C NMR study of the mode of interaction in solution of the B fragment of staphylococcal protein A and the Fc fragments of mouse immunoglobulin G. AB - The mode of interaction of the B domain (FB) of staphylococcal protein A and the Fc fragments of mouse immunoglobulin G (IgG) has been investigated by 13C NMR spectroscopy. Mouse IgG1, IgG2a, and IgG2b proteins have been selectively labeled with 13C at the carbonyl carbon of His, Met, Trp or Tyr residue and used to prepare the corresponding Fc fragments by limited proteolysis. Site-specific resonance assignments have been made for each of these Fc analogues. FB was reported to form two contacts (contact 1 and contact 2) with human Fc in the crystal [Biochemistry 20 (1981) 2361-2370]. Comparisons of the chemical shift data of the Fc fragments observed in the absence and presence of FB have led us to conclude that in solution contact 1 is responsible for the formation of the Fc FB complexes. PMID- 8344436 TI - Endothelin-receptor interactions. Role of a putative sulfhydryl on the endothelin receptor. AB - The mechanism of action of endothelin-receptor interactions was studied, using radioligand binding assays and SDS-PAGE, to investigate the possibility of disulfide interchange. Electrophoretic analysis suggested involvement of disulfide bond(s) in the receptor-ligand complex. Treatment of Et receptors with sulfhydryl-specific alkylating reagents (NEM or others) resulted in decreased ability to bind [125I]Et-1. [Dpr1-Asp15]Et-1, an antagonist homologous to Et but with an amide link replacing one of the disulfides, bound to Et receptors reversibly, but binding of Et-1 was less reversible. Preincubation of receptors with Et-1, but not with [Dpr1-Asp15]Et-1, protected receptors from alkylation with [14C]NEM. The data suggest that the Et receptor has a sulfhydryl group at or near the Et binding site. A model is proposed in which the role of the putative sulfhydryl group is discussed. PMID- 8344437 TI - Proper processing of a G protein gamma subunit depends on complex formation with a beta subunit. AB - G protein beta and gamma subunits function as a tightly associated complex. We show that complex formation with the beta subunit is a critical step for post translational processing of a gamma subunit. When expressed alone in a cell line, the gamma 3 subunit type is isoprenylated but degraded; co-expression with the beta 1 subunit type stabilizes the gamma 3 protein. Furthermore, our experiments with partial cell fractionation indicate that the gamma 3 protein is localized differently in the cell depending on whether or not it is bound to the beta subunit. Binding of the gamma subunit to the beta subunit is thus one of the prerequisites for the appropriate intracellular localization of the beta gamma complex and potentially, for normal G-protein function. PMID- 8344438 TI - Regulation by growth factors (IGF-I, b-FGF and TGF-beta) of proto-oncogene mRNA, growth and differentiation of bovine adrenocortical fasciculata cells. AB - Nuclear proto-oncoproteins have been implicated in the regulation of gene expression by peptidic hormones and growth factors during cell proliferation and differentiation. In the present study we have investigated in bovine adrenal cells (BAC) the effects of basic fibroblast growth factor (b-FGF), insulin-like growth factor 1 (IGF-I) and transforming growth factor beta (TGF-beta) on c-jun, jun-B and c-fos mRNA levels and on cell growth and differentiation. Factors able to enhance the three proto-oncogenes (IGF-I, b-FGF and angiotensin II (A-II)) stimulate cell growth, whereas those inhibiting cell growth (TGF-beta and ACTH) decrease c-jun mRNA level. These results suggest that expression of c-jun may be required to induce cell proliferation. The relation between proto-oncogenes and the expression of differentiated functions appears to be more complex. Whereas IGF-I, b-FGF and A-II increase the three nuclear proto-oncogenes, the effects of IGF-I and b-FGF on cytochrome P450 17 alpha-hydroxylase mRNA levels are opposite to those of A-II. On the other hand, while TGF-beta and A-II have inhibitory effects on P450 17 alpha mRNA level, they have opposite effects on c-jun mRNA. PMID- 8344439 TI - The relationships between transketolase, yeast pyruvate decarboxylase and pyruvate dehydrogenase of the pyruvate dehydrogenase complex. AB - The amino acid sequences of four thiamine pyrophosphate-requiring enzymes were aligned with the published amino acid sequence of the transketolase of Hansenula polymorpha. Sequences of the combined alpha and beta subunits of the E1 enzyme of the pyruvate dehydrogenase complexes of Homo sapiens and Bacillus stearothermophilus aligned well with the transketolase while the E1 of the pyruvate dehydrogenase complex of Escherichia coli aligned easily provided a non aligning segment of 77 amino acids was omitted. The non-acetylating pyruvate decarboxylase of Saccharomyces cerevisiae could only be aligned if the sequence was cut in two with the C-terminus corresponding to the N-terminus of the other TPP-dependent enzymes. Using the published 2.5 A resolution of the X-ray crystal structure of Saccharomyces cerevisiae transketolase as a template we show that a hydrophobic region of the beta-subunit of the PDH E1 alpha beta enzymes likely contains a binding site for the thiazolium ring of TPP and key motifs are retained in common by all the TPP-dependent enzymes considered, which are essential for catalysis. PMID- 8344440 TI - A compendium of reviews in biochemistry and molecular biology published in the second half of 1992. AB - 1. A compendium of reviews and mini-reviews in Biochemistry and Molecular Biology published in the second half of 1992 is presented. In all 776 titles are listed from 108 different publications. 2. This compendium presents the references by Journal Name. Keywords have been included with each reference to increase the value of the collection. Keyword and author cross-reference indexes are not included but are available in the electronic database from which this version was constructed. Should anyone wish to have this information in electronic form it can be distributed on MS-DOS formatted floppy disks in either Reference Manager or Medline format. The author should be contacted for details of the number of preformatted floppy disks required. PMID- 8344441 TI - Lectins and superantigens: membrane interactions of these compounds with T lymphocytes affect immune responses. AB - 1. Lectins and superantigens belong to two different families of macromolecules which are able to interact with cells of the immune system. 2. The principal mechanisms by which they modulate immune responses are presented in this review. 3. Possible similarities shared by these proteins and their common mechanisms of action upon immunocytes will be presented along with a brief discussion regarding the role of these molecules in physiological immune responses and human diseases. PMID- 8344442 TI - Microfilaments and protein synthesis; effects of insulin. PMID- 8344443 TI - Effect of Berenil on polyamine metabolism in primary cultured rat hepatocytes. AB - 1. Putrescine and spermidine content increased in hepatocytes during culture. In the presence of 10 microM Berenil, putrescine content was further increased, while the increase of spermidine was prevented. 2. Ornithine decarboxylase activity was markedly reduced, and to a lesser extent also S-adenosylmethionine decarboxylase activity. 3. Berenil appears to promote an increase in the transformation of spermidine into putrescine, and to inhibit the polyamine efflux. PMID- 8344444 TI - Cloning and characterization of rabbit pancreatic colipase. AB - 1. Among the digestive enzymes synthesized by pancreas, lipase is the principle lipolytic enzyme which hydrolyses dietary glycerides. 2. For its action it requires a coenzyme, colipase. 3. The molecular mechanisms of the interaction of these two are not fully understood. 4. Further, molecular events that regulate and influence lipid absorption are ill defined. 5. The rabbit is the conventional animal model for the study of lipid absorption. We have undertaken the molecular cloning, and characterization of rabbit pancreatic colipase, the coenzyme for pancreatic lipase. 6. Colipase has been cloned from a gt 11 library of an adult rabbit pancreatic cDNA by probing with an oligonucleotide derived from human colipase sequence. 7. The total reading frame consists of 321 nucleotides coding for 90 amino acids of the functional protein and 17 nucleotides of the leader peptide. 8. Northern blot analysis revealed a distinct band around 0.5 kb. Comparison with other species revealed an over all homology of 75% at the nucleotide level. 9. At the amino acid level highest conservation is observed at the lipase-binding region (AA 53-73). 10. Rabbit enzyme also retained the N terminal pentapeptide of its preform. 11. The regions of homology and conservation may aid to define the sites of interaction of colipase with lipase. PMID- 8344445 TI - Algal phospholipids by 31P NMR: comparing isopropanol pretreatment with simple chloroform/methanol extraction. AB - 1. A modified Folch procedure [potassium (ethylenedinitrilo)-tetraacetic acid at pH 6 substituted for KCl] is suitable for the extraction of marine algae. 2. The quantitative 31P nuclear magnetic resonance phospholipid profiles of four marine algae, Gracilaria verrucosa, Bryothamnion triquetrum, Padina gymnospora, and Caulerpa sertularioides, were obtained from Folch and Nichols extractions of both fresh and dried algae, and essentially identical results were obtained using either extraction procedure. 3. Extracts of air-dried algae are statistically different when compared to extracts of living algae, suggesting that tissue handling is a critical factor in phospholipid extractions. PMID- 8344446 TI - Inhibitory effects of alpha- and beta-carotene on croton oil-induced or enzymatic lipid peroxidation and hydroperoxide production in mouse skin epidermis. AB - 1. The effects of carotenes (alpha- and beta-) on edema, MDA contents and peroxidizability of croton oil-treated mouse skin epidermis, hydroperoxide production and enzymatic lipid peroxidation of epidermal homogenates were studied. Edema was determined as ear punch weight and the intensity of lipid peroxidation was measured using malondialdehyde formation. 2. Carotenes (alpha- and beta-) significantly suppressed edema formation, hydroperoxide production, lipid peroxidation caused by croton oil, Fe + 3-ADP/NADPH or paraquat/NADPH in vivo as well as in vitro. 3. These results indicate that both alpha- and beta carotene have chemopreventive effects on croton oil-induced tumor promotion in skin tumorigenesis by scavenging oxygen free radicals, indirectly determined as carotene inhibition of lipid peroxidation and hydroperoxide formation. PMID- 8344447 TI - Demonstration of highly specific and sensitive antibodies to a naturally occurring tetrahydroisoquinoline alkaloid, salsolidine. AB - 1. We report for the first time on the production and characterization of antibodies against a naturally occurring tetrahydroisoquinoline, namely salsolidine (6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline). 2. Immunogen synthesis was carried out by coupling the hapten salsolidine to bovine serum albumin (BSA) as carrier protein on the basis of reductive amination. 3. By immunization of rabbits with salsolidine-BSA conjugate antisalsolidine antibodies were produced. 4. At a final dilution of 1:1700 the highest-titre antiserum bound 35% of 0.21 pmol [3H]salsolidine. This antiserum was used to develop a radioimmunoassay for salsolidine. 5. Cross-reactivity studies revealed a high specificity of the antiserum to the hapten. 6. The antibodies had a high affinity to salsolidine (Ka = 1.5 x 10(9) M-1). 7. Standard curves covered a measuring range of 0.5-70 pmol/tube and the detection limit was found to be 0.27 pmol/tube. PMID- 8344448 TI - Molecular geometry of antigen binding by a monoclonal antibody against 5 methylcytidine. AB - 1. The specificity of a monoclonal IgG1 raised against a 5-methylcytidine-keyhole limpet hemocyanin conjugate was investigated by inhibition experiments with soluble competing antigens. 2. A competitive enzyme immunoassay has been set up, with the antigen immobilized on polystyrene microtitration wells. 3. The analysis of the cross-reaction profile allowed the topography of the antigen-antibody interaction to be described. 4. The binding properties of the monoclonal antibody are discussed in terms of both analytical applications and working limitations in the immunochemical study of gene methylation. PMID- 8344449 TI - Differential expression of salivary mucin bacterial aggregating activity with caries status. AB - 1. The low and high mol. wt mucin forms were isolated from saliva of caries resistant (CR) and caries-susceptible (CS) individuals, and assessed for their bacterial aggregating potential towards S. mutans and S. sanguis, the common cariogenic microorganisms encountered in the oral cavity. 2. The high mol. wt mucin from both groups of subjects exhibited similar protein and carbohydrate content, but the level of covalently bound fatty acids was significantly lower in the CR group. The mucin from CR group showed only a weak inhibitory potential, and no inhibitory activity was observed with the mucin of CS group. 3. The low mol. wt mucins from both groups, while displaying compositional similarities, showed a marked variation in the bacterial aggregating activity. With both bacteria, the activity of the mucin from CR group was at least 128-fold greater than that of CS group. 4. The conversion of the high mol. wt mucin to a low mol. wt form through the action of salivary protease produced in both groups enhancement in mucin's bacterial aggregating capacity. This enhancement was, however, considerably less pronounced in the case of mucin from CS group. 5. The results for the first time demonstrate that the bacterial aggregating epitope of salivary mucins is expressed to a greater extent in CR individuals, and that this epitope is apparently more accessible to bacteria in the low mol. wt mucin form. PMID- 8344450 TI - In vitro non-enzymatic glycosylation of myofibrillar proteins. AB - 1. Glycation is non-enzymatic modification of proteins by sugars in which not only structural but also biological properties of proteins are altered. 2. Our in vitro experiments show that incubation of myofibrillar proteins with ribose results in sugar attachment to proteins and at the same time myofibrillar ATPase activity is lowered. 3. DETAPAC, aminoguanidine and 2-mercaptoethanol all partially block myofibrillar protein glycation and ATPase activity is less inactivated. 4. The dependence of ATPase activity of myofibrils incubated with ribose on the amount of 2-mercaptoethanol present suggests that also modification of SH groups is involved in enzyme inactivation. 5. Electrophoretic studies revealed that heavy chains of myosin, actin, and tropomyosins are proteins which are mainly glycated in vitro. PMID- 8344452 TI - Restoration of motor unit properties and fiber type distribution in reinnervated axolotl skeletal muscle. AB - The contractile properties of functionally isolated motor units and the muscle fiber type distribution of reinnervated iliotibialis posterior muscles were examined in axolotls (Ambystoma mexicanum) 7 to 12 months after complete transection of the hind limb nerve trunks. Motor units were continuously distributed with respect to size and contractile speeds and there was a positive correlation between motor unit size and twitch:tetanus ratio. The degree of overlap between motor units was positively correlated with motor unit size and inversely correlated with similarity of contractile speeds. In addition, the muscle fiber type distribution within the reinnervated muscles, as revealed by immunocytochemical localization of tonic, slow, and fast myosin isoforms, was indistinguishable from that in the contralateral unoperated muscles, with no evidence of fiber type grouping. Thus, the motor organization after reinnervation was very similar to that of normal muscles examined previously. The only difference found was that a small number of motor units contracted unusually rapidly in reinnervated muscles. The absence of muscle fiber type redistribution and the essentially normal motor unit characteristics suggest that the original pattern of synaptic connections was reestablished following reinnervation. These observations are consistent with the returning motor neurons selectively reinnervating their original muscle fiber types. PMID- 8344451 TI - Ecdysteroid induction of embryonic morphogenesis in a parasitic wasp. AB - Development of the parasitic wasp Copidosoma floridanum (Hymenoptera: Encyrtidae) is unusual in two ways. As many as 3000 embryos are formed from a single egg and embryonic morphogenesis is closely synchronized with the onset of the metamorphosis of its host. Given this extreme synchrony between parasite and host development, we undertook a series of experiments to determine whether host endocrine factors regulate C. floridanum embryonic morphogenesis. Here we report that C. floridanum embryos must develop for 9 days before acquiring the competence to undergo morphogenesis. Furthermore, several pieces of evidence suggest that ecdysteroids of host origin regulate induction of C. floridanum morphogenesis. First, competent embryos initiated morphogenesis when transplanted into host larvae and pupae, host stages possessing elevated ecdysteroid titers, but not when transplanted into adult moths. Second, morphogenesis was arrested by ablation of the host's source of ecdysone, but could be rescued by injection of 20-hydroxyecdysone in a dose-dependent manner. Finally, a segment of DNA encoding a zinc finger nearly identical in sequence to a portion of the ecdysone receptor of Drosophila melanogaster was isolated and characterized from C. floridanum. This putative ecdysone receptor probe indicated that expression of this gene was correlated with the initiation of C. floridanum embryonic morphogenesis. The temporal pattern of putative receptor RNA accumulation increased in association with the onset of morphogenesis, while the spatial pattern of expression was associated with the invagination of cells forming the gastrula. Together, these data suggest that ecdysone of host origin is directly involved in the induction of C. floridanum embryonic morphogenesis. PMID- 8344453 TI - The proliferation of mature oligodendrocytes in vitro is stimulated by basic fibroblast growth factor and inhibited by oligodendrocyte-type 2 astrocyte precursors. AB - Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) are mitogens for bipotential oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells. We investigated the mitogenic effect of these growth factors on quiescent mature oligodendrocytes (OL) expressing myelin basic protein (MBP) in OL cultures that were treated for 3 days with cytosine arabinoside (ARA-C) in order to kill O 2A precursors which divide in chemically defined medium. After treatment with ARA C proliferation decreased and O-2A precursors identified with A2B5 monoclonal antibody were nearly undetectable. After exposure of mature OL to bFGF, cell proliferation increased markedly within 24 hr. PDGF had a much weaker effect. Cultures treated with ARA-C for 3 days and then with bFGF for the next 24 hr and incubated with BrdU for the last 2 hr before the end of the experiment were immunolabeled with anti-MBP or A2B5 and anti-bromodeoxyuridine (BrdU) antibodies. Eighty-seven percent of the cells were MBP+, 10% were both MBP+ and BrdU+, and none was A2B5+ BrdU+, showing that at least a part of the population of mature MBP+ OL retains the ability to reenter the cell cycle in vitro. Since mature OL did not proliferate in response to bFGF in the cultures not treated with ARA-C, i.e., in the presence of O-2A progenitors, we assumed that these precursors were responsible for the lack of mitogenic effect of bFGF on MBP+ OL in such conditions. Conditioned medium from O-2A precursors almost halved the bFGF induced OL proliferation after treatment with ARA-C, suggesting that O-2A progenitors control the proliferation of a subpopulation of mature OL (possibly young mature OL) via the secretion of active molecule(s). PMID- 8344454 TI - MAP kinase becomes stably activated at metaphase and is associated with microtubule-organizing centers during meiotic maturation of mouse oocytes. AB - Using antisera generated against sequences conserved between the ERK1- and the ERK2-encoded species of mitogen-activated protein (MAP) kinases of the rat, species of approximate M(r) 42 and 44 kDa were identified in mouse oocytes. When oocytes underwent meiotic maturation, both species displayed a retarded electrophoretic mobility, consistent with modification by phosphorylation. The slow-migrating forms first appeared after the oocytes had entered metaphase, and their appearance was sensitive to inhibitors of protein synthesis or phosphorylation. These forms remained throughout maturation and in oocytes arrested at metaphase II. Following oocyte activation, which induces a transition to interphase, the slow-migrating forms were replaced by the fast-migrating forms observed in prophase oocytes. MAP kinase activity also increased after oocytes entered metaphase, and this increase required protein synthesis and phosphorylation. To investigate the intracellular distribution of the immunoreactive species, spindles were purified from metaphase II eggs. Both the 42- and the 44-kDa species were detected in immunoblots, and bright staining of the spindle poles was observed by immunofluorescence. When intact oocytes undergoing maturation were examined by immunofluorescence, foci of staining were initially detected on opposing sides of the condensing chromosomes and then became congregated at each pole of the first meiotic spindle. No localized staining was observed during the first meiotic division, but stained foci were present at the poles of the second meiotic spindle. In addition, several cytoplasmic foci of staining often could be seen. When oocytes were exposed to taxol, which permits nonspindle microtubule-organizing centers (MTOCs) present in the cytoplasm to nucleate microtubule assembly, the cytoplasmic foci labeled by the MAP kinase antibodies were found to contain tubulin. We conclude that mouse oocytes contain 42- and 44-kDa species of MAP kinase and that, after maturing oocytes enter metaphase, MAP kinase activity is stimulated by means of a process requiring protein synthesis and phosphorylation. MAP kinase is present in the spindle and is specifically associated with the MTOCs present at the spindle poles and in the cytoplasm. Evidence from cell-free systems suggests that the alterations in MTOC activity that normally occur at metaphase in oocytes may be regulated by MAP kinase. The association of MAP kinase with MTOCs provides a potential structural basis for this cell cycle-dependent change in MTOC activity. PMID- 8344455 TI - Induction of polarizing activity by retinoic acid occurs independently of duplicate formation in developing chick limb buds. AB - Retinoic acid (RA) is known to mimic the action of the zone of polarizing activity (ZPA) in inducing the formation of anteroposterior duplicates in the chick limb bud. Although RA had been thought to be a morphogen produced by the ZPA, recently we (Noji et al., 1991) and Wanek et al. (1991) independently concluded that RA induces polarizing activity in cells at the anterior margin of the chick limb bud. In this study, we examined the distribution of RA-induced polarizing activity in the limb bud. At first, RA-containing beads were implanted into various regions of stages 20-23 limb buds. After 24 hr, we grafted tissue fragments from sites adjacent to the RA beads into the anterior margin of host limb buds. High polarizing activity was induced in anterior-distal and apical mesoderm regions immediately under the apical ectodermal ridge (AER) when beads presoaked in 1 mg/ml RA were grafted to anterior sites at stages 19-20. However, in mesoderms distant from the AER, even if adjacent to the implanted RA bead, only low activity was induced. Although implantation of beads soaked in a high concentration (10 mg/ml) of RA did not result in duplications but rather in truncations of the limbs, the apical mesodermal cells in these limbs were converted to ZPA cells, indicating that induction of polarizing activity by RA can occur independently of duplicate formation. The ability to respond to RA treatment was rapidly lost in the cells along the anterior margin of stage 22 limb buds. When the anterior AER was removed, the induction of polarizing activity in the anterior margin of limb buds was markedly reduced. Thus, the AER seems to be necessary for the RA-directed induction of polarizing activity. PMID- 8344456 TI - SpOct, a gene encoding the major octamer-binding protein in sea urchin embryos: expression profile, evolutionary relationships, and DNA binding of expressed protein. AB - We have characterized a sea urchin gene, SpOct, that encodes a 78-kDa POU-domain protein related to mammalian Oct-1 and Oct-2. The SpOct protein binds octamer elements in the promoters of the alpha H2B (Bell et al., 1992, Dev. Biol. 150, 363-371) and CyIIIa actin genes, and it closely resembles the major octamer binding activity obtained from sea urchin blastula nuclear lysates in the size of its DNase I footprint on a canonical octamer element and in its relative binding affinity (Kr) for the octamer element versus poly(dAT) (1.4 x 10(4)). Moreover, partial protein sequences obtained from affinity-purified octamer-binding protein match sequences present in SpOct. These data suggest that SpOct is closely related to, if not identical with, the major octamer-binding activity in blastula nuclear extracts. RNA gel blots reveal four forms of SpOct mRNA, ranging in size from 4 to 12 kb. They are regulated coordinately in the embryo: all are present in the unfertilized egg, increase 28-fold in amount by the 8-hr blastula stage, and decline 6-fold by the 12-hr blastula stage. The same four size classes of SpOct mRNAs are present in several adult tissues, although their relative amounts vary. The temporal profile of SpOct mRNA expression in embryos closely resembles that of the alpha histone H2B gene. Our previous work (Bell et al., 1992) showed that expression of the alpha H2B gene in blastula-stage embryos was entirely dependent on an octamer element. Together, these data strongly suggest that SpOct may be the key regulator of the alpha H2B gene. PMID- 8344457 TI - Selective pathway choice of a single central axonal fascicle by a subset of peripheral neurons during leech development. AB - In the CNS of leech, the central projections of peripheral sensory neurons segregate into three distinct axonal tracts during early development. We have previously shown that a subset of these neurons, recognized by the monoclonal antibody lan 4-2, projects axons into only one of these fascicles (Johansen et al., 1992, Neuron 8, 599). Here we report on a developmental and biochemical characterization of another fascicle-specific antigen labeled by the monoclonal antibody lan 3-6. By immunocytochemistry and double labelings we demonstrate that the lan 3-6 epitope is expressed only by a small subgroup of the peripheral neurons in Macrobdella embryos. The axons of these neurons selectively fasciculate in the CNS, but to only one of the three lan 3-2-positive tracts, which is different from the previously described lan 4-2-positive tract. These observations support the existence of a hierarchy of guidance cues mediating specific tract formation in this system. A biochemical analysis of the antigen suggests that it is likely to be a glycosylated protein with a molecular weight of approximately 200 kDa. Thus, the restricted expression of the lan 3-6 antigen and its biochemical properties are consistent with the hypothesis that this antigen may be playing a role in axonal guidance. PMID- 8344458 TI - Secretion of cumulus expansion enabling factor by mouse oocytes: relationship to oocyte growth and competence to resume meiosis. AB - Fully grown mouse oocytes secrete a factor that enables the surrounding cumulus cells to undergo cumulus expansion upon stimulation of the cumulus cells with follicle-stimulating hormone in vitro. The secretion of the enabling factor by the oocytes is developmentally regulated; it is normally secreted in significant amounts only by oocytes that are competent of undergoing spontaneous germinal vesicle breakdown (GVB) and resuming the first meiotic division. The objective of this study was to determine the relationship, if any, among secretion of this factor, oocyte growth, and the competence to undergo GVB. Three experimental systems were used to assess these relationships. First, 20 to 25% of the oocytes isolated from the small antral follicles of mutant hypogonadal mice were GVB incompetent even though they had achieved a size typical of GVB-competent oocytes. These large GVB-incompetent oocytes secreted almost as much cumulus expansion enabling factor as the GVB-competent oocytes. Second, GVB-incompetent oocytes cultured under conditions that promote the acquisition of GVB competence but not oocyte growth acquired the ability to secrete the cumulus expansion enabling factor. Third, the precocious activation of maturation promoting factor (MPF) in GVB-incompetent oocytes by okadaic acid did not stimulate the secretion of cumulus expansion enabling factor. It is concluded that the secretion of cumulus expansion enabling factor by oocytes is (1) independent of oocyte growth, (2) independent of competence to undergo GVB, and (3) not induced by the precocious activation of MPF. Thus, although the secretion of the enabling factor normally coincides with the time of acquisition of competence to undergo GVB, the ability to secrete the enabling factor is independent of oocyte maturation. Nevertheless, factors that promote the oocyte's program that leads to competence to undergo GVB probably also promote the ability to secrete the enabling factor. PMID- 8344459 TI - ZAP-1 DNA binding activity is first detected at the onset of zona pellucida gene expression in embryonic mouse oocytes. AB - ZAP-1 (zona pellucida gene activating protein-1) is a putative transcription factor controlling the oocyte-specific expression of mouse and human zona pellucida genes. The DNA binding activity of ZAP-1 first appears in oocytes from 19-day-old mouse embryos and reaches a maximum level at 10 days after birth. This developmental profile closely parallels that of mouse zona pellucida gene transcription, which is detected in oocytes at 19 days of fetal life using a sensitive RT-PCR method and is maximal in 10-day-old animals. DNA binding activity similar to that of ZAP-1 is present in ovarian extracts from rat, human, and opossum, suggesting that the ZAP-1 protein may be conserved among mammals. PMID- 8344460 TI - TGF-beta 1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteases. AB - Using an in vitro model of rat epiphyseal chondrocyte differentiation in which cells are maintained in a three-dimensional cell pellet, we show that exogenous TGF-beta 1 reversibly prevents terminal differentiation of epiphyseal chondrocytes into hypertrophic cells. Through maintenance of gene expression for the cartilage matrix proteins type II collagen and aggrecan core protein, and with coordinate inhibition of expression of genes encoding the metalloproteases collagenase and stromelysin, TGF-beta 1 stabilizes the phenotype of the prehypertrophic epiphyseal chondrocyte. This ability of TGF-beta 1 to stabilize the cartilage phenotype is critically dependent on culture conditions. Epiphyseal chondrocytes cultured as a subconfluent monolayer of cells dedifferentiate (reduce type II collagen and aggrecan core protein expression, increase metalloprotease expression, and acquire a spindled morphology) in response to short-term TGF-beta 1 treatment. Increasing the initial seeding density and allowing the cells to become multilayered prior to the addition of growth factor reverse the effects of TGF-beta 1 on type II collagen and transin/stromelysin gene expression and maintain a rounded cellular morphology. This finding emphasizes the importance of considering cell density and environmental context in the analysis of the regulatory action of peptide growth factors in general and of the TGF-beta s in particular. We propose that one function of TGF-beta 1 during endochondral ossification is regulation of chondrocyte growth and differentiation through modulation of the relative expression of cartilage matrix proteins and metalloproteases. This function of TGF-beta 1 helps illustrate how the regulation of diverse cellular processes such as matrix synthesis, matrix degradation, and cell growth and differentiation may be coordinated at the molecular level by a single peptide growth factor. PMID- 8344461 TI - The role of the tracheae and musculature during pathfinding of Drosophila embryonic sensory axons. AB - Developing sensory axons were studied in Drosophila embryos which carried a mutation in the trachealess and/or the twist gene. In these embryos, the tracheae and/or somatic muscles, which represent part of the substrate on which sensory axons normally grow, are absent. The results demonstrate that in each of these three mutant backgrounds, the majority of sensory nerves form normally. This indicates that neither the tracheae nor the somatic musculature is absolutely required for pathfinding of the embryonic sensory axons. On the other hand, the incidence of misrouted axons is significantly increased, most strongly in the trh, twi double mutant. Furthermore, axonal elongation is considerably slowed down, and sensory neurons which fail to send out an axon are frequent. We take our results to indicate that peripheral axons in the Drosophila embryo may be guided by multiple cues which, acting together, ensure the high fidelity of axonal pathways observed in normal development. The removal of one of these cues by itself does not necessarily lead to the total disability of axons to reach their target, although it enhances the frequency of error in pathfinding. PMID- 8344462 TI - Selective repression of actin and myosin heavy chain expression during the programmed death of insect skeletal muscle. AB - The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta undergo two sequential changes in mass at the end of metamorphosis. Atrophy results in a 40% loss of muscle mass beginning 3 days before adult eclosion (emergence). Coincident with eclosion, the ISMs undergo programmed cell death that results in the complete destruction of the muscles during the subsequent 30 hr. These developmental changes are initiated by sequential decreases in the circulating titer of the ecdysteroids. While the molecular basis of ISM atrophy is largely unknown, the commitment of the muscles to die has been shown to require the repression of specific genes and the activation of others. Data presented here suggest that two of the repressed genes encode the proteins actin and myosin heavy chain. Expression of both actin and myosin heavy chain mRNA was greatly decreased when the ISMs became committed to die. When animals were treated with 20-hydroxyecdysone, cell death was delayed and the loss of these transcripts was reduced. At the protein level, actin expression was reduced by 84% at the time the muscles were committed to die. The reduction in actin and myosin heavy chain synthesis presumably plays a role in the rapid dissolution of the muscles. PMID- 8344463 TI - Induction of T alpha 1 alpha-tubulin mRNA during neuronal regeneration is a function of the amount of axon lost. AB - Axotomy of mature peripheral neurons leads to upregulation of T alpha 1 alpha tubulin mRNA. To distinguish whether this increase is due to interruption of target contact or to loss of the axon itself, we developed a model system that allowed us to axotomize mature sympathetic neurons proximal or distal to their cell bodies, severing contact with target tissue in all cases. Sympathetic neurons within the same superior cervical ganglion that project via the internal and external carotid nerves to the eye and to the ear, respectively, were differentially labeled with the retrograde tracers fast blue and fluorogold, and the labeled neurons were then transected close to or far from their cell bodies. In situ hybridization analysis 5 days postaxotomy (the time of peak T alpha 1 mRNA expression) indicated that when eye and ear neurons were both axotomized close to their cell bodies. T alpha 1 mRNA increased to a similar degree in both populations. In contrast, when ear neurons were again cut close, but eye neurons of the same ganglion were transected far from their cell bodies by eye removal, peak T alpha 1 mRNA levels were two- to threefold lower in the eye neurons. Thus, the increase in T alpha 1 mRNA was much lower when only a small amount of axon was lost, even though contact with target tissue was completely interrupted in all groups. These results therefore suggest that neurons normally monitor the status of their axon via a mechanism that allows for graded responses and that the axotomy-induced increase in T alpha 1 mRNA is, to a great extent, due to loss of the nonterminal axon. PMID- 8344465 TI - A female sterile mutant, unfertilizable (uf), in Xenopus laevis. AB - We describe a female sterile mutant, unfertilizable (uf), in Xenopus laevis whose eggs cannot be fertilized by either natural mating or artificial insemination. The uf eggs were able to be activated by pricking with a fine glass needle. Ultraviolet-solubilized jelly from the uf eggs could permit the fertilization of the dejellied wild-type eggs by artificial insemination, while uv-solubilized jelly from the wild-type eggs did not permit the fertilization of the dejellied uf eggs. The uf eggs, whose jelly coats and vitelline envelopes were removed, could be fertilized by insemination in the uv-solubilized jelly from either wild type or uf eggs. These results show that the eggs and the jelly coats are intact but the vitelline envelopes are abnormal in uf mutant eggs. One- and two dimensional gel electrophoretic comparisons of vitelline envelopes from wild-type and uf eggs demonstrated that five protein components, having estimated molecular masses of about 26, 64, 69, 78, and 250 kDa, were present in the vitelline envelopes of uf eggs but were absent in those of wild-type eggs. All of these components were polymorphic in terms of isoelectric points. Thus the cause of unfertilizability of uf eggs resides in the vitelline envelopes whose protein components exceed those of the wild-type eggs. PMID- 8344464 TI - Alternative splicing of a neural-specific Src mRNA (Src+) is a rapid and protein synthesis-independent response to neural induction in Xenopus laevis. AB - Alternative splicing is used by the src protooncogene to derive two gene products, pp60c-src and pp60+. pp60+ is expressed exclusively in neurons, whereas pp60c-src is expressed in many tissues. The specific role of the src+ gene product in neurons is not yet understood. Expression of src+ mRNA begins early in neural development and is restricted to the neural plate in Xenopus embryos. Using a reverse transcription/polymerase chain reaction assay, we demonstrate that expression of src+ mRNA is dependent on neural induction. Src+ mRNA is expressed in animal cap ectoderm which is cocultured with mesoderm tissue, but not in ectoderm cultured alone. The protein kinase C (PKC) activator 12-O tetradecanoylphorbol-13-acetate (TPA) induces src+ mRNA expression in cultured stage 10+ animal cap ectoderm. This induction is rapid, with src+ mRNA being detected within 1 hr of TPA addition. Only dorsal ectoderm tissue is competent to express src+ mRNA upon TPA treatment, and stage 10+ ectoderm tissue becomes unresponsive to TPA after 4 hr in culture. TPA-dependent induction of src+ mRNA in ectoderm tissue is not blocked by cycloheximide and therefore is not dependent on protein synthesis. PMID- 8344466 TI - Origin of fetal troponin T: developmentally regulated splicing of a new exon in the fast troponin T gene. AB - We have identified a new exon in the fast troponin T (TnT) gene whose alternative splicing is developmentally regulated. In previous studies three novel isoforms of TnT were identified in fetal and neonatal rabbit skeletal muscles (Briggs et al., 1990, Dev. Biol. 140, 253-260). These proteins are recognized by an antibody against fast TnT, but no combination of the previously identified exons could explain their protein chemical properties. To determine whether an additional exon is present in the fast TnT gene, we have cloned and sequenced cDNAs from fetal rabbit muscle RNA. Reverse transcription coupled to PCR was used with primers from conserved regions of the fast TnT sequence that span the 5' alternatively spliced exons. Sequences were obtained for each of the fetal TnTs. All included known fast TnT coding sequences plus an additional 36 nucleotides between exons 8 and 9. The peptide predicted from this sequence is highly acidic and accounts for the chemical properties of the fetal proteins. Similar experiments analyzing neonatal rat TnT cDNAs identified an homologous sequence, and comparison with the genomic sequence revealed that it is encoded by a single exon. Thus, fetal TnTs are generated from the fast TnT gene by the inclusion of a new, alternatively spliced exon, which we have designated f (for fetal), whose developmentally regulated splicing appears to be a common feature of mammalian skeletal muscle development. PMID- 8344467 TI - Absence of somatic histone H1 in oocytes and preblastula embryos of Xenopus laevis. AB - Available data on the occurrence and expression of somatic histone H1 during oogenesis and early embryogenesis of Xenopus laevis are contradictory. In particular the reported presence of a large storage pool of histone H1A in oocytes is difficult to reconcile with the high transcriptional activity of all gene classes in this specific cell type. In the present study we have used polyclonal antibodies raised against somatic Xenopus histone H1 (H1A and H1A/B) for combined immunoblotting experiments to quantitate H1 pools and immunolocalization studies to visualize chromosome-bound H1. Both approaches failed to detect soluble or chromosomal histone H1 in vitellogenic oocytes, eggs, and cleavage-stage embryos up to early blastula. In addition, chromatin assembled in Xenopus egg extract was also negative for histone H1 as revealed by immunofluorescence microscopy. Lampbrush chromosomes not only lacked histone H1 but also the previously identified histone H1-like B4 protein (Smith et al., 1988, Genes Dev. 2, 1284-1295). In contrast, chromosomes of eggs and early embryos fluoresced brightly with anti-B4 antibodies. Our results lend further support to the view that histone H1 expression is developmentally regulated during Xenopus oogenesis and embryogenesis similar to what is known from other species. PMID- 8344468 TI - Tracing the incorporation of the sperm tail in the mouse zygote and early embryo using an anti-testicular alpha-tubulin antibody. AB - The mechanism of sperm tail incorporation and the fate of the tail during mouse fertilization and early embryogenesis were examined. Time-lapse video microscopy and anti-tubulin immunofluorescence show that the incorporation of the sperm tail, but not the sperm head, is sensitive to cytochalasin B (a microfilament inhibitor). Colcemid, a microtubule inhibitor, does not affect tail incorporation. High-resolution, low-voltage scanning electron microscopy demonstrates that the plasma membrane covering the sperm tail does not appear to fuse with the oocyte membrane during in vitro fertilization in the presence of cytochalasin. In control and colcemid-treated oocytes, the plasma membrane along the sperm tail, which is oriented tangential to the egg surfaces, appears to fuse with the oocyte membrane at multiple sites. An antibody to testicular alpha tubulin detects sperm-derived, but not egg, microtubules and this has permitted us to trace the behavior and disappearance of the sperm tail during embryogenesis. Conventional and confocal microscopy show that following sperm incorporation, the tail often splays into multiple fibers. At the two-cell stage, the axoneme may be localized in either blastomere or it may be found to run through the midbody between both blastomeres. The tail appears to shorten by the 8-cell stage and is undetectable after the 16-32 cell stage. In morulae, tail fragments have been found in outer cells but not in inner ones, and fragments have not be found in blastocysts. These data suggest that microtubules of sperm and oocytes contain different isotypes of alpha-tubulin, nongenomic sperm-derived components survive at least to the morula stage of mouse development, and egg microfilaments are involved in the incorporation of the sperm tail but not the sperm head, which demonstrates that motility during sperm incorporation is different in mammals when compared to lower vertebrates and invertebrates. PMID- 8344469 TI - Embryonic expression of Fgf-6 is restricted to the skeletal muscle lineage. AB - As part of an ongoing examination of the functions of the fibroblast growth factor (FGF) gene family in mammalian development, we have carried out an RNA in situ hybridization analysis of the Fgf-6 gene in the mouse embryo. In contrast to what has been found for three other members of the FGF gene family, no Fgf-6 RNA was detected in mouse embryos at E6.5 through E8.5. Fgf-6 RNA was first detected in embryos at E9.5 and was localized exclusively in the myotomal compartment of the somite. Similar results were obtained with embryos at E10.5 and E11.5. At E12.5, expression was still detected in the myotome, and also in the region containing the developing muscles of the body wall. By E14.5, Fgf-6 RNA was found in the majority of skeletal muscles in the fetus. These results are discussed in comparison with what is known about the expression patterns of the genes encoding other FGF family members, as well as their high-affinity receptors. PMID- 8344471 TI - Correlation of forelimb malformation asymmetries with visceral organ situs in the transgenic mouse insertional mutation, legless. AB - We studied the relationship between the sidedness of visceral organs and the expression of limb abnormalities in the legless mutant. The control of asymmetry in visceral development appears to be random in the legless mutant; that is, 50% develop normally (situs solitus) and 50% develop with inverted viscera (situs inversus). We find that the sidedness of forelimb abnormalities expressed in the mutants is highly correlated with visceral sidedness. Abnormalities are more severe in the right forelimbs in situs solitus mutants, while the left forelimb is more severely affected in situs inversus mutants. PMID- 8344470 TI - Role of epidermal growth factor expression in early mouse embryo lung branching morphogenesis in culture: antisense oligodeoxynucleotide inhibitory strategy. AB - Epidermal growth factor (EGF) expression and branching morphogenesis were inhibited using a 5' 15-mer antisense oligodeoxynucleotide (ODN) directed against EGF precursor mRNA in embryonic mouse lung in culture under chemically defined, serumless conditions. Antisense EGF ODN resulted in > 90% inhibition of EGF immunoreactive peptide synthesis, 75% reduction in branching morphogenesis, 73% decrease in DNA content, 64% decrease in RNA content, 73% decrease in protein synthesis, and 65% decrease in [3H]thymidine incorporation into DNA compared to Embryonic Day 11 controls in culture for 4 days. Sense ODN results were similar to control. Supplementing antisense ODN with EGF partially reversed antisense effects. The results further support a role for EGF in pulmonary organogenesis. PMID- 8344472 TI - Individual susceptibility to noise-induced hearing loss: an old topic revisited. AB - The wide range in susceptibility to noise-induced hearing loss has intrigued researchers and hearing conservationists alike. Some of these differences in variability have been attributed to various intrinsic factors such as eye color, gender, age, etc. However, a review of controlled research shows that the influence of these intrinsic variables is relatively small and cannot explain the wide range of hearing loss observed in demographic studies. Furthermore, uncontrolled variables or unrecognized drug and noise interaction may obscure the relation between noise exposure and hearing loss. With the growing understanding of the physiology of the auditory system, new possibilities are emerging that may explain the range of susceptibility. A review of the role of acoustic reflex effectiveness, cochlear efferent function, and history of noise exposure provide a perspective for future strategies in predicting susceptibility to noise-induced hearing loss. PMID- 8344473 TI - Concurrent right and left ear auditory brain stem response recording. AB - In auditory brain stem response testing, it is often advantageous to record the responses to right and left ear stimulation quickly. A method is described in which both ears are tested concurrently, each ear at a slightly different stimulus rate. With appropriate temporal parameters, the response of each ear can be recorded without contamination by the contralateral ear's response. When both ears were tested at the same intensity, either 40 or 70 dB nHL, there was little attenuation of wave V. When one ear was stimulated at 80 dB nHL, the response of the other ear at intensities down to 40 dB was not seriously affected; the response at 20 dB nHL was, however, so diminished by contralateral stimulation at 80 dB that binaural testing would save no time. This method has promise for intraoperative monitoring and infant screening, and could be used in threshold determination if the stimulus intensities for the two ears are not too dissimilar. PMID- 8344474 TI - Auditory brain stem responses to air- and bone-conducted clicks in the audiological assessment of at-risk infants. AB - Auditory brain stem responses (ABRs) to air- and bone-conducted clicks were used to assess the auditory status of 170 at-risk neonates. During the perinatal period, 20.6% (35/170 cases) of the at-risk infants failed ABRs to air-conducted clicks at 30 dB nHL in at least one ear. Ear-specific results indicated an initial failure rate of 15.0% (51/340 ears). Approximately two-thirds (32/51 ears) of these initial failures showed purely conductive deficits, whereas the remaining one-third (19/51 ears) involved suspected sensorineural components. Follow-up audiological evaluations were performed for 87.1% (148 cases) of these at-risk infants at 4 mo and/or 1 yr corrected age. Based on the initial tests and follow-up assessments, the tentative operating characteristics of ABRs to both air- and bone-conducted clicks for identification of sensorineural deficits in at risk neonates were calculated. It was found that the ABR to bone-conducted clicks yielded better specificity, predictive value of positive results, and overall efficiency. It is suggested that the ABR to bone-conducted stimuli should be viewed as a valuable addition in the assessment of cochlear reserve in infants who fail a newborn auditory screening to air-conducted stimuli. PMID- 8344475 TI - Temporal masking of human auditory evoked brain stem responses using two simultaneously presented maximum length sequences. AB - Two simultaneously presented maximum length sequences (MLSs) were used to investigate temporal nonlinearities. Not only did the recorded auditory evoked brain stem responses to these stimuli predictably increase in latency and decrease in amplitude as a function of the temporal interactions between MLSs, but thresholds were elevated by more than 20 dB. Simultaneous MLS paradigms make it possible to investigate a number of nonlinearities in the auditory system efficiently. This study also demonstrated that binaural MLS techniques can be used to assess auditory function even in individuals with asymmetric hearing losses without fear of crossover effects. PMID- 8344476 TI - Frequency discrimination in listeners with sensorineural hearing loss. AB - The difference limen for frequency (DLF) was measured in both ears of 34 hearing impaired subjects at the octave and interoctave frequencies between 500 and 4000 Hz. In agreement with previous studies of DLF in the hearing impaired, there was only a moderate correlation (0.49) between DLF/F and hearing threshold level (HTL). Correlation and regression analyses at the individual frequencies, however, indicated that DLF/F is much more closely related to HTL at 1000 Hz and above than it is below 1000 Hz. Comparison of the right-left ear differences in DLF and HTL revealed some large DLF differences where there was no HTL difference and some large HTL differences where no DLF difference was found. The lack of a strong relationship between DLF and HTL asymmetries indicates that the structures that limit the DLF and the HTL may, at the same frequency, be damaged differently in each ear of the same subject. PMID- 8344477 TI - A videotape analysis procedure for assessing conversational fluency in hearing impaired adults. AB - This article describes a method for analyzing conversational difficulties and communication breakdown management in hearing-impaired adults and their communicative partners. The focus of the analysis is placed on the examination of conversational floor control, the proportion of repaired and nonrepaired communication breakdowns, and the strategies used by each member of the dyad to repair breakdowns. A case study illustrating the application of the procedure for aural rehabilitation is presented. PMID- 8344478 TI - Speech recognition in noise by children with minimal degrees of sensorineural hearing loss. AB - It is well recognized that the acoustical environment in a classroom is an important variable in the psychoeducational achievement of hearing-impaired children. To date, however, there remains a paucity of information concerning the importance of classroom acoustics for children with minimal degrees of sensorineural hearing loss (SNHL). The present investigation examined the effects of commonly reported classroom signal to noise ratios (+6, +3, 0, -3, and -6 dB) on the sentence recognition of 20 normal-hearing children and 20 children with minimal degrees of SNHL (i.e., pure-tone averages of 15-30 dB HL through the speech frequency range). Results indicated that children with minimal degrees of SNHL obtained poorer recognition scores than normal-hearing children across most listening conditions. Moreover, the performance decrement between the two groups increased as the listening environment became more adverse. Educational implications of these data, such as acoustical modification of the classroom and/or the utilization of frequency modulation sound field amplification systems, are discussed. PMID- 8344479 TI - Is disordered speech production a consequence of adventitious deafness? A comment to Leder and Spitzer. PMID- 8344480 TI - Tumor suppressor genes--the hope. PMID- 8344481 TI - Genes that can antagonize tumor development. PMID- 8344482 TI - Tumor suppressor genes studied by cell hybridization and chromosome transfer. AB - Although the cloning of tumor suppressor genes has proved to be an arduous task, often involving several years of labor intensive cloning strategies, a greater understanding of neoplastic progression will be made once the function and role of these genes have been sorted out. To fully appreciate the state at which this field of research currently is, however, one must understand that the road to tumor suppression was paved by both somatic cell hybridization and chromosome transfer studies. Although regarded by many as laboratory artifact, somatic cell hybridization has provided strong circumstantial evidence, if not formal proof, for the existence of tumor suppressor genes. In further reducing the complexity associated with whole genome transfer, single chromosome transfer was subsequently developed as a refinement to this technique so that one could unequivocally correlate suppression with a particular chromosome. We have learned from these studies that single chromosomes harbor the genetic information necessary to reverse the malignant phenotype associated with cancer cells. Furthermore, multiple tumor suppressor loci are now known to exist, with one to several different loci associated with a given tumor type. In this review, we present evidence for tumor suppressor genes and discuss the early studies that led to their discovery. PMID- 8344483 TI - Mechanisms of reversion. AB - Reversion of transformed cells provides biological system useful in multiple areas of cancer research. First, reversion can be induced by inhibiting the activities of specific oncogenes or replacing intact tumor suppressor genes, and such experiments yield important insights into the roles of these genes in carcinogenesis and normal growth regulation as well as the functional relationships between these genes and other known genes. Second, novel genes involved in growth regulation can be discovered by isolating revertants from transformed cells after mutagenesis or DNA transfection and then characterizing the genes responsible for the non-transformed phenotype. Third, potential anti cancer drugs can be screened by reversion assay using cells transformed by specific oncogenes. The novel genes and chemicals discovered through these studies serve as valuable tools that help our understanding of how cells regulate their growth and differentiation. PMID- 8344484 TI - Speculations on the roles of RB1 in tissue-specific differentiation, tumor initiation, and tumor progression. AB - Studies of retinoblastoma clearly identify mutation of the RB1 gene on chromosome 13 as the primary cause of this cancer. However, all retinoblastoma tumors have an abnormal karyotype (1, 2) indicating the presence of additional mutations and suggesting that mutation of both RB1 alleles is insufficient for development of retinoblastoma. In addition, analysis of RB1 expression and of RB1 mutations in different tumors leads to the following dilemma: while the RB1 gene product, p110RB1, is expressed in most dividing cells, germline mutations inactivating the function of p110RB1 predispose primarily to retinoblastoma and to a lesser extent to osteosarcoma, but do not predispose to cancer in general. However, many tumors contain somatic mutations that disrupt RB1 function. Thus, we are faced with the unusual situation in which germline mutations in the RB1 gene predispose to a very limited set of cancers, but somatic mutations in RB1 appear to contribute to malignancy in many tissues. We propose that the role of the RB1 gene is to maintain the cells in a stable, quiescent state required for terminal differentiation and that the effect of RB1 mutations in different tissues depends on the pattern of differentiation in that tissue. In tissues where differentiation follows a linear process from undifferentiated precursors to fully differentiated cells, loss of RB1 function during early stages of differentiation may lead to uncontrolled growth and the development of cancer. On the other hand, in cell renewal systems where cell number is usually maintained by a process of programmed cell death (PCD) or apoptosis, loss of RB1 function may lead to cell death. PMID- 8344485 TI - A comparison of the biological activities of wild-type and mutant p53. AB - Tumorigenesis is characterized by a series of genetic alterations in both dominant oncogenes and tumor suppressor genes. A hallmark of tumor suppressor genes is that both alleles are generally altered during transformation, which usually represents a loss of function phenotype. The p53 tumor suppressor gene is the most frequently affected gene detected in human cancer. There is now growing evidence suggesting that mutation of p53 may involve not only a loss of function of wild-type p53 activity but also a gain of function phenotype contributed by the mutant p53 protein. The study of the biological properties and functions of both wild-type and mutant p53 is central to our understanding of human cancer. These properties and functions of wild-type and mutant p53 will be compared and contrasted here and elsewhere within this thematic issue. In addition, the mechanisms of inactivation of p53 function, which include: 1) mutation, 2) inhibition by viral oncogene products, 3) inhibition by cellular regulators, and 4) alteration in subcellular localization, will be discussed. PMID- 8344486 TI - Interactions between SV40 large-tumor antigen and the growth suppressor proteins pRB and p53. AB - The oncogenic property of simian virus 40 depends in large part on the function of the virus-coded T-antigen. Although the precise mechanism of how T functions during neoplastic transformation is not clear, some answers to this question may lie in our understanding the nature of the proteins found to complex with T. The cellular protein p53 is perhaps the most extensively studied protein in this regard. Recently, p53 was defined as a growth suppressor protein. At about this same time, T was found to complex with another cell growth suppressor protein, the product of the retinoblastoma susceptibility gene. It has since become apparent that complex formation between these proteins affects their individual growth-modulating activities. Quite often this alteration of activity correlates with an uncontrolled proliferative state of the cell. Thus, transformation by SV40 is thought to involve complex formation between the viral T oncoprotein and cellular growth suppressor proteins. This complex formation is believed to result in nullification of the growth suppressor protein properties, thus increasing the propensity of the cell toward uncontrolled growth, the hallmark of neoplastic transformation. PMID- 8344487 TI - Interaction of adenoviral proteins with pRB and p53. AB - The transforming gene products of the small DNA tumor viruses subvert host cell growth control mechanisms by binding to specific cell regulatory proteins. These include the retinoblastoma gene product (pRB) and p53. One indication of the pivotal roles played by these regulatory products is the observation that they are each targeted consistently by viruses of several groups, by adenoviruses, the human papillomaviruses, and the papovaviruses. In adenovirus, pRB and p53 are targeted by the E1A and E1B genes, respectively. The genetic probes made possible by manipulation of the virus genes in vitro have helped to illuminate the pathways in which pRB and p53 function. E1A studies have contributed to our current understanding that the retinoblastoma product is one of a family of related proteins, which with associated cyclins and kinases can modulate the activity of the cellular E2F transcription factor. E1B studies have helped explore models of p53 function, including the suggestion that p53, probably through aspects of its transcription regulating activity, can initiate a pathway in which programmed cell death can be invoked to stop unrestricted cell proliferation. PMID- 8344488 TI - Multiple steps in carcinogenesis involving alterations of multiple tumor suppressor genes. AB - Recent advances in molecular genetics have made it possible to understand the molecular mechanisms of human cancer progression. The results indicate that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration occurs during tumor progression. It is widely accepted that tumor suppressor genes play a central role in the genesis and progression of human cancers, as frequent alterations of tumor suppressor genes have been found in a variety of human cancers. Molecular analyses of various stages of human cancers, from precancerous lesions to advanced or metastatic tumors, indicate that sequential accumulation of genetic alterations correlates with more malignant phenotypes of tumor cells. Furthermore, biological studies of tumor suppressor genes have revealed that a single gene defect is not sufficient for the cells to gain growth advantage and start clonal expansion in vivo. These results are consistent with the concept of human multistage carcinogenesis, indicated by experimental animal models and epidemiological studies. Although it is supposed that there are more than 20 tumor suppressor genes in the human genome, only a few tumor suppressor genes have been identified to date. Thus, further studies should focus on the identification and characterization of novel tumor suppressor genes, and molecular analysis of those genes in human cancer would be of great help in clarifying the multiple steps in the process of human carcinogenesis. PMID- 8344489 TI - Gene and chromosomal alterations associated with the development of human gliomas. AB - The development of a malignant tumor generally entails a series of events that damage the genome of a somatic cell and result in the malignant phenotype. These events chronicle the malignant progression of a tumor; a dynamic process in which more aggressive and growth-deregulated cell populations are constantly evolving. Gliomas, the most common primary tumors of brain, are known to become increasingly malignant with time. Within recent years, several details of the molecular genetic events associated in their progression have been determined. The earliest events of glioma progression include loss of genetic information from the long arms of chromosomes 13 or 22, or the short arm of chromosome 17 for which targeting of the TP53 (p53) gene has been indicated. Loss of a single complement of type I interferon (IFN) genes from 9p and loss of genetic information from 19q are seen in the tumors of intermediate malignancy grade. Events associated with the most malignant of glial tumors include loss of the second, type I IFN gene complement, loss of genetic information from chromosome 10, and gene amplification (most commonly the epidermal growth factor receptor, in 40% of cases). These findings have helped elucidate the events associated with glial tumorigenesis, and through the identification of specific genes, have provided a starting point for investigating the molecular biology of central nervous system neoplasia. PMID- 8344490 TI - RB1 protein in normal and malignant human colorectal tissue and colon cancer cell lines. AB - The pattern of human retinoblastoma (RB1) gene protein expression was directly examined in normal and malignant human colorectal tissues and in seven colorectal carcinoma cell lines by immunohistochemistry using the mouse monoclonal antibody (RB-MAb-1) directed against the retinoblastoma protein (RB). This is the first demonstration of RB immunostaining in adult human colonic epithelium and colorectal carcinomas. Specificity using RB-MAb-1 was confirmed by western blot analysis, which showed bands of 110-116 kDa corresponding to the sizes of unphosphorylated and phosphorylated RB. RB staining of normal adult colonic epithelium was confined to the nucleus and was most intense in the transitional zone of the crypt, whereas lumenal cells (fully differentiated) were RB negative. Primary colorectal carcinomas and all the colon cancer cell lines stained positively for nuclear RB, but the expression was heterogeneous with varying fractions of RB negative cells present. Because we and others have previously shown that loss or inactivation of the RB1 gene is infrequent in colorectal carcinomas, reduced RB expression in such cells is probably due to a cellular regulatory mechanism. For example, RB negative cells may be those in early-G1 phase (known to have reduced RB levels) or growth-arrested cells that have differentiated. The ability to directly detect RB in primary colorectal carcinomas will permit assessment of whether heterogeneous expression of the RB1 gene product has prognostic significance for survival of patients with this cancer. PMID- 8344491 TI - Genetic background alters the spectrum of tumors that develop in p53-deficient mice. AB - Using gene targeting in embryonic stem cells, we have generated mice with one or two null p53 germ line alleles. Mice with both p53 alleles inactivated are developmentally normal but highly susceptible to the early development of spontaneous tumors. Initial studies were performed in mice with a mixed inbred genetic background (75% C57BL/6 and 25% 129/Sv) (Donehower et al., Nature (London) 356, 215-221, 1992). To study the effect of genetic background on tumorigenesis in p53-deficient mice, we have put the p53 null allele into a pure 129/Sv background and monitored tumor development. 129/Sv mice with two p53 null alleles developed tumors sooner than the mixed genetic background p53-deficient animals. The most frequently observed tumor in p53 null mice of both genetic backgrounds was a malignant lymphoma. Because the 129/Sv strain has a low incidence of lymphoma, the frequent occurrence of lymphomas in all p53 null mice suggests that this particular tumor type may be a direct result of p53 loss and not a result of a particular genetic background. In addition to malignant lymphomas, the 129/Sv p53-deficient mice showed an increased incidence of aggressive teratocarcinomas (8 of 18 tumor-bearing males), a tumor type rare in virtually all inbred mice except for 129 strains. Thus, it appears that loss of p53 may accelerate a prior tumor predisposition and that genetic background can play a role in mediating both the rate and spectrum of tumor development in these mice. PMID- 8344492 TI - Dosage-dependent dominance over wild-type p53 of a mutant p53 isolated from nasopharyngeal carcinoma. AB - Mutational inactivation of p53, a tumor suppressor gene, is the most common genetic alteration found in human cancer. Most mutated p53s either lose tumor suppressor function or gain oncogenic activity. We recently reported the detection of a heterozygous point mutation of p53 at codon 280 in nasopharyngeal carcinoma (NPC) (1), a high-incidence malignancy in southern China and southeast Asia. Given its heterozygous state, in which both wild-type and mutated p53 gene were expressed, p53-thr280 should function dominantly in the presence of the wild type form if it is to play a role in nasopharynx carcinogenesis. We tested this dominance hypothesis in the cells of two model systems: 1) human Saos-2 cells lacking endogenous p53, and 2) mouse JB6 tumor promotion-resistant cells (P-) expressing endogenous wild-type p53. The results showed dosage-dependent dominance of p53-thr280 in controlling WT p53-driven transcriptional activity; in governing cell growth; and in progressing P- phenotype to tumor promotion sensitive (P+) phenotype. This dominant negative effect was seen at a 1:1 (WT:MU) ratio and was more striking at a ratio of 1:3. A model is proposed to explain the dominant negative effect of mutant p53. We conclude from this study that p53 thr280 is likely to be dominant in the heterozygous state found in NPC and that this dominant-negative mutated p53 may contribute to the genesis of NPC or of other carcinomas in which both mutant and wild-type p53 are expressed. PMID- 8344493 TI - Hemi- or homozygosity: a requirement for some but not other p53 mutant proteins to accumulate and exert a pathogenetic effect. AB - Activating mutations within the p53 gene cause stabilization and therefore increased steady-state levels of the p53 protein; some, but not all, also result in the generation of an epitope recognized by the antibody pAB240. We have shown here that in 70% of Burkitt lymphoma cell lines, but not in normal EBV transformed B cell lines, p53 protein is readily detectable by Western blot analysis using either an antibody directed against the 240 epitope or an antibody against wild-type p53. Genomic analysis of these BL cell lines demonstrated the presence of mutations within the p53 gene in all cell lines with detectable p53 protein. We have also shown that in the cell lines ST486, Raji, and TE 110, which are heterozygous for a neutral sequence codon polymorphism (Arg/Pro) that causes altered migration of an otherwise normal protein and also contain a heterozygous mutation, only the protein derived from the mutated allele is stabilized. Thus the dominant effect of the mutations present in these cell lines apparently does not result from sequestering of the normal protein by the abnormal protein, and therefore presumably is a consequence of a gain-of-function resulting from the mutation. Although all cell lines with stabilized p53 also contained p53 mutations, three lymphoid tumors (two cell lines and one fresh B-CLL) with a heterozygous mutation at codon 248 did not express elevated levels of p53. In contrast, p53 was readily detectable in Western blot analysis from cell lines KK124, Namalwa, and CA46, which had homo- or hemizygous mutations at codon 248, and from PP1084, a cell line with a codon 273 mutation and a carboxyl-terminal truncation in the other allele. These results suggest that mutations at codon 248, unlike those in cell lines ST486 and TE110, are stabilizing only in the absence of the wild-type p53. Heterozygous mutations at codons 248 have been described in the germline of individuals belonging to cancer-prone families described by Li and Fraumeni (see ref 18), but tumors detected in such individuals are homozygous, i.e., contain only mutated p53. This is consistent with the possibility that such mutations exert a pathogenetic effect only in the absence of the wild-type protein, and are coupled to our findings that stabilization of p53 is a necessary component of the oncogenic pathways relevant to p53. However, whereas some mutations are stabilizing in the presence of the normal p53 protein, others are stabilizing only in the homozygous state. PMID- 8344494 TI - Identification of mutations in p53 that affect its binding to SV40 large T antigen by using the yeast two-hybrid system. AB - The tumor suppressor p53 protein binds to the products of several viral oncogenes, including SV40 large T antigen. We reconstructed the p53-T antigen interaction in the yeast two-hybrid system, a genetic assay that uses the reconstitution of the activity of a transcriptional activator to detect protein protein interactions. Using mutants of T antigen known to be defective in binding to p53, we demonstrate that the two-hybrid system is more sensitive than immunoprecipitation in the detection of weak interactions. We mutagenized the murine p53 gene and screened in the yeast assay for decreased reporter gene expression indicative of the failure of p53 to bind T antigen. This screen identified 34 p53 mutants, almost all of which contain at least one mutation in the conserved domains frequently found mutated in human cancers. These results support the idea that the function of the wild-type p53 protein requires residues involved in binding to T antigen, and indicate that this approach may be generally applicable in the analysis of protein-protein interactions. PMID- 8344495 TI - Identification by differential display of alpha 6 integrin as a candidate tumor suppressor gene. AB - A new method of differential expression cloning called differential display (DD) has been used to screen for novel tumor suppressor genes involved in breast cancer. The screen is based on positive selection at the mRNA level for genes expressed in normal mammary epithelial cells but decreased or lost in corresponding tumor cells. A candidate tumor suppressor gene recovered by DD is integrin alpha-6 (alpha 6), a component of the heterodimeric integrin receptors alpha 6 beta 1 and alpha 6 beta 4. Loss of alpha 6 expression was confirmed in total RNAs by Northern blot analysis and by immunostaining with alpha 6 antibodies. Consistent with these cell culture findings, previous immunostaining of mammary tissue sections has identified decreased alpha 6 protein expression during breast tumor progression. Southern blot analysis demonstrated that alpha 6 gene is present in tumor cell lines, suggesting that reexpression may be inducible by pharmacological intervention. The likelihood that alpha 6 may have tumor suppressing activity is supported by growing evidence of a central role for integrins in transducing growth control and differentiation signals from growth factors and the extracellular matrix (ECM). PMID- 8344496 TI - How tumour suppressor genes were discovered. PMID- 8344497 TI - Serum and gastric mucosal pepsinogens in atrophic gastritis, particularly in type A gastritis associated with pernicious anemia in Japanese. AB - The levels of serum pepsinogen I (PG I) and pepsinogen II (PG II) were determined by IRMA (immunoradiometric assay) and the ratio of PG I/II calculated in 37 patients with type A gastritis and concomitant pernicious anemia (PA) and in 97 with chronic gastritis (type B gastritis) among Japanese. In several patients from each group, PG I and PG II in the gastric mucosa were stained by an enzyme antibody assay to compare the percentage of positively stained cells with levels of serum PG I and PG II. The levels of serum PG I and PG II in chronic gastritis decreased as the degree of atrophy increased. Serum PG I and PG II levels in PA were lower than those of patients with severe atrophy. Most of serum PG I levels in PA were less than 10 ng/ml. The PG I/II ratio also decreased as the severity of atrophy increased, distinctly showing that in PA, the ratio were quite low and most of them are less than 1.0. Gastric mucosal pepsinogen showed a tendency similar to that of serum levels and also refrected the degree of atrophy. Therefore, by measuring these parameters it should be easier to determine the extent of atrophy, and to establish a serological diagnosis of type A gastritis associated with PA. PMID- 8344498 TI - Gastric motility and ischemic changes in occurrence of linear ulcer formation induced by restraint-water immersion stress in rat. AB - The pathogenesis of linear ulceration induced by restraint water-immersion (RWI) was investigated in view of gastric motility and early ischemic changes. After three hours of restraint-water immersion stress, the cross-sectioned gastric body was prepared for light microscopy. Most lesions (90.8%) were present in the mucosal folds projecting toward the cavity. Wedge-shaped degeneration in the crest of the folds was recognized as an ischemic lesion followed by hemorrhagic ulceration. Compressed arterioles were frequently encountered in the muscularis mucosae and circular muscle. Generally, mucosal folds appear merely with the reduction of gastric content, and run along with the elevation of the circular muscle as an anatomical structure, becoming tall and steep after RWI. Marked enhancement of contraction, observed with a strain gauge force transducer, was induced by RWI. This enhancement was suppressed by papaverine HCl pretreatment in accordance with suppression of the fold-related mucosal lesion even after 150 mM HCl perfusion into the stomach. In conclusion, gastric motility appears to play an important role in the pathogenesis of linear ulceration by causing ischemic change along the folds. PMID- 8344499 TI - Surgical experience with 5 n3(+) early gastric carcinoma cases. AB - Of 370 patients who underwent a resection for early gastric carcinoma, 317 (85.6%) were N(-), 28 n1(+), 20 n2(+) and five (1.4%) n3 respectively. In this study, n3(+) early gastric cancers were clinicopathologically evaluated and sites of the metastatic nodes were also defined. In addition, a comparative study in DNA ploidy patterns between primary and metastatic node cell was performed according to Hedley's method using a FACS-IV scan of paraffin-embedded tissues. All n3(+) early gastric cancers showed an aneuploidy pattern. R2 or R3 operations are recommended for early gastric carcinomas with aneuploidy pattern and most of the metastatic nodes arise from the identical stem cell line of cancer cells. PMID- 8344500 TI - Relationship between amino acid transport and protein synthesis in rat isolated pancreatic acini under stimulation with cholecystokinin. AB - The effects of cholecystokinin octapeptide (CCK8) on amino acid transport and protein synthesis in the pancreatic acini were determined. The question of whether those effects differed between amino acid transport systems A and L was also investigated. The influx of alpha-[3H]aminoisobutyric acid (AIB, system A) and [14C]cycloleucine (system L) into isolated rat pancreatic acini and the incorporation of [14C]alanine (system A) and [3H]leucine (system L) into trichloroacetic acid (TCA)-precipitable protein in pancreatic acini were studied in the presence of various concentrations of CCK8. CCK inhibited the amino acid transport across the basolateral membrane of pancreatic acini. This effect was mediated by Ca2+, and was more responsive to amino acid transport system L than to A. CCK also inhibited protein synthesis in pancreatic acini in a dose dependent manner. The inhibition of protein synthesis by CCK was thought to be mainly due to the inhibition of amino acid transport by CCK. Therefore, the predominant utilization of extracellular amino acids in protein synthesis was suggested. PMID- 8344501 TI - Plasma lipase, C-peptide reactivity and human pancreatic polypeptide responses after ingestion of elemental diet in patients with chronic pancreatitis. AB - Plasma lipase, C-peptide reactivity (CPR) and human pancreatic polypeptide (HPP) responses after ingestion of elemental diet were studied in 27 patients with chronic pancreatitis. These subjects were classified into 3 groups according to ERP findings; minimum or mild (MIP, n = 17), moderate (MOP, n = 6) and advanced (ADP, n = 4). Basal plasma lipase levels in the MIP and MOP patients were significantly higher than that in the controls (P < 0.05). Plasma CPR response (sigma delta CPR) in MIP cases were significantly higher than that in controls (P < 0.05). Also, plasma HPP (response (sigma delta HPP) in MIP cases were significantly higher than that in controls (P < 0.05). Plasma CPR and HPP responses correlated with the severity of chronic pancreatitis. Fourteen of the 17 MIP patients (82%) showed higher levels of basal lipase or sigma delta HPP in comparison to the respective normal ranges. This study suggested that the ED test may be more sensitive for detection of mild chronic pancreatitis and that it may be useful for evaluating exocrine and endocrine pancreatic functions in various stages of chronic pancreatitis. PMID- 8344503 TI - Solitary pedunculated polypoid gastric gland heterotopia. AB - A solitary pedunculated gastric polyp in the gastric fundus was removed from an asymptomatic 36-year-old woman with normal gastric acid secretion and a normal serum gastrin level. This lesion exhibited distinctive histological features including prominent proliferation of pseudopyloric glands, fundic glands, foveolar epithelium and a fibromuscular stroma. Moreover, its surface was entirely covered by a layer of normal gastric epithelium. Biopsies of the background mucosa taken from the gastric fundus revealed only mild superficial gastritis. A gastric gland heterotopia was diagnosed because of its unique morphology. PMID- 8344502 TI - Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones. AB - In Japan the composition of gallstones is changing rapidly from the once predominant brown-pigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 +/- 10 vs. 146 +/- 8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 alpha hydroxy-4-cholesten-3-one 12 alpha-hydroxylase (12 alpha-hydroxylase), the rate limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 alpha-hydroxylase and 12 alpha-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis. PMID- 8344505 TI - A case report of celiac axis compression and implications in regional chemotherapy for liver metastasis. AB - Regional chemotherapy through a catheter placed in the hepatic artery is routinely used for treatment of unresectable liver metastasis from colon carcinoma. With some frequency, anatomical variations of the hepatic artery, including compression of the celiac axis, are found, and must be recognized preoperatively for appropriate management and placement of the catheter. We report a case of a colon cancer patient with multiple liver metastases and compression of the celiac axis, who received decompression of the celiac axis and catheterization of the hepatic artery. PMID- 8344504 TI - Detection of focal nodular hyperplasia of the liver with color Doppler ultrasonography. AB - A 3-cm lesion indicative of focal nodular hyperplasia (FNH) of the liver was coincidentally detected in a 21-year-old female. Ultrasonography (US), computed tomography (CT), magnetic resonance (MR) imaging and liver scintigraphy all proved nonspecific. However, color Doppler US demonstrated characteristic vascular patterns of FNH of the liver, including (a) hypervascularity of the mass, (b) an enlarged afferent blood vessel in the tumor with blood flow toward the center of the tumor, and (c) arterial pulse waves in all the vessels in the lesion, detected by means of the fast Fourier transformation (FFT). With selective hepatic angiography, a "spoke-wheel" pattern was revealed. The angiographic pattern corresponded well to that shown by color Doppler US. On the basis of the findings from these two modalities, the diagnosis of FNH was made. This report examines the effectiveness of color Doppler US in the differential diagnosis of FNH, compared with other imaging modalities. PMID- 8344507 TI - Novel sterol 7 alpha-hydroxylase(s) active towards not cholesterol but side-chain oxygenated steroids in liver microsomes. PMID- 8344506 TI - Hepatic triglyceride lipase mRNA expression in various liver diseases. PMID- 8344508 TI - Depressed mood and care preferences in patients with AIDS. AB - Eight hundred ninety-seven patients with AIDS seen in ambulatory settings were questioned about whether they would accept a nursing home or a respirator if necessary to prolong their lives. Two hundred ninety-one (32.9%) said they would accept a nursing home; 102 (11.5%) said they would accept a respirator. Acceptability of these life-sustaining interventions was significantly lower in those patients who showed evidence of clinical depression on a structural screening instrument (nursing home: 29.4% vs 39.5%, p = 0.002; respirator: 9.4% vs 14.3%, p = 0.032). Depression remained significant in multivariate models of care preferences that controlled for demographics and symptom severity. Based upon follow-up interviews conducted an average of 11 months later, subjects who were initially depressed and found nursing home care unacceptable were significantly more likely to have changed their minds at follow-up if their depression was no longer present (45.7% vs 28.4%; p = 0.0005). Findings for respirator preferences were similar, but did not attain significance. We conclude that assessment for depression is essential when advance directives for care are elicited from patients with AIDS. PMID- 8344509 TI - Somatization. Why can't we see the forest for the trees? PMID- 8344510 TI - Admission patterns of persistent somatization patients. AB - Persistent somatization patients put a serious burden on the health care system with multiple admissions, tests, surgeries, and medications. This study reports on factors relevant to the health-seeking behavior of somatizing patients and aspects of the health care system that facilitate their overutilization of health resources. Individuals (age 17-49 years) from the general population of two Danish municipalities with at least 10 general admissions during an 8-year period were studied comparing persistent somatizers with other high utilizers of medical admissions. Results are reported on geographical mobility, change in family doctors, route and distribution of admissions by time of day or week, discharges against medical advice, physical disease overlooked, and distribution of admissions to specialties. Although the health-seeking behavior of persistent somatizers may in part explain their overutilization of health care resources, such overutilization could be reduced and much suffering avoided if physicians displayed the same enthusiasm in diagnosing somatization as in ruling out organic pathology. PMID- 8344511 TI - Culture and psychiatric epidemiology in Japanese primary care. PMID- 8344512 TI - Lifetime prevalence of specific psychiatric disorders in a general medicine clinic. AB - Using a two-stage case identification method, the Japanese version of the General Health Questionnaire (GHQ) and the Japanese modified Diagnostic Interview Schedule (DIS-JM), patients in a general medicine clinic in Japan were assessed for psychiatric disorders (DSM-III categories) during a 12-month period. The lifetime prevalence of all psychiatric disorders was 30.6%, excluding tobacco dependence. The most prevalent diagnoses were alcohol abuse and dependence 9.4%, psychosexual dysfunction 5.9%, and major depressive episode 4.7%. The predominant disorders in males were alcohol abuse and dependence and tobacco dependence, and in females (aged 55-80 years), the most striking disorder was organic brain syndrome. The validity of the GHQ was examined against the DIS-JM based on DSM III as external criteria. A cutoff point between 7 and 8 is suggested. PMID- 8344513 TI - A survey of psychiatric consultations at a suburban emergency room. AB - The utilization of psychiatric crisis teams in urban hospitals is well documented. However, little is reported describing patients who use crisis teams in suburban general hospital emergency rooms. This is a descriptive survey of 1707 suburban patient visits. This study relates patient demographics with the length of time required to provide crisis intervention and disposition. A regression model is used to analyze the duration of service time and utilization patterns in relation to eight variables: season, month, day, shift, diagnosis, method of payment, age, and disposition. Five predictors are identified as significantly relating to the duration of the psychiatric consultation process. These predictors may enable hospital administrators and medical staff to plan and implement psychiatric emergency room care. PMID- 8344514 TI - Establishing a consultation-liaison psychiatry clinical database in an Australian general hospital. AB - This paper describes the institution of a clinical database in the consultation liaison psychiatry service of an Australian general hospital psychiatry unit. One of the problems faced was that many researchers and clinicians in Australia use the ICD-9 rather than the DSM-III-R classification system. Nevertheless, it was possible to use the DSM-III-R-based MICRO-CARES clinical database management system in this project. The data obtained during the first 12 months of its use are presented. Despite differences in the patient demographic characteristics, the data obtained are within the ranges described for North American and European sites. The local benefits of such a clinical database are described, and it is argued that such a database is also necessary for interhospital and international collaborative studies and comparisons. PMID- 8344515 TI - Clinical interpretation of the mini-mental state. AB - The Mini-Mental Status Examination (MMSE) is a brief, structured test of cognitive function. The test is often used as a screening or case-finding instrument for the detection of organic mental disorders or cognitive impairment. However, many clinicians incorporate the MMSE into their clinical mental status examination. In both contexts, cutoff scores are often utilized to interpret the results, with scores below the cutoff being interpreted as evidence of cognitive dysfunction, and scores above the cutoff being interpreted as evidence against such dysfunction. However, when the test is done as part of a mental status examination, the application of a cutoff score fails to take account of prior clinical information, which is critical to the interpretation of all diagnostic tests. In this paper, an alternative approach to interpretation is proposed. In the proposed method, guidelines for interpretation are based on the probability of being free of organic disease at each potential score. Scores are interpreted in terms of their consistency or inconsistency with a prior diagnostic impression. This takes prior clinical information and clinical judgment into account. Although different from the traditional way of interpreting the MMSE, the proposed method can be implemented on an intuitive level and does not require mathematical calculations, which are inconvenient at the bedside. PMID- 8344516 TI - The use of midazolam for hypnosedative interviews. AB - The authors describe three cases in which midazolam was successfully used in diagnostic hypnosedative interviews. A discussion comparing and contrasting midazolam to other intravenous hypnosedatives is presented. The authors suggest that midazolam is an effective agent for diagnostic hypnosedative interviews and may be preferable to other agents when posthypnotic recollection of interview content is undesirable. PMID- 8344517 TI - Hybridization and DNA sequence analyses suggest an early evolutionary divergence of related biosynthetic gene sets encoding polyketide antibiotics and spore pigments in Streptomyces spp. AB - The whiE gene cluster of Streptomyces coelicolor, which is related to gene sets encoding the biosynthesis of polycyclic aromatic polyketide antibiotics, determines a spore pigment. Southern blotting using probes from three different parts of the whiE cluster revealed related gene sets in about half of a collection of diverse Streptomyces strains. A 5.2-kb segment of one such cluster, sch, previously shown to determine spore pigmentation in Streptomyces halstedii, was sequenced. Seven open reading frames (ORFs), two of them incomplete, were found. Six of the ORFs resemble the known part of the whiE cluster closely. The derived gene products include a ketosynthase (= condensing enzyme) pair, acyl carrier protein and cyclase, as well as two of unidentified function. The seventh ORF diverges from the main cluster and encodes a protein that resembles a dichlorophenol hydroxylase. Comparison with sequences of related gene sets for the biosynthesis of antibiotics suggests that gene clusters destined to specify pigment production diverged from those destined to specify antibiotics early in the evolution of the Streptomyces genus. PMID- 8344518 TI - A plasmid system for high-level expression and in vitro processing of recombinant proteins. AB - A novel plasmid expression system has been constructed that combines two useful functions: it facilitates single-step affinity purification of cytoplasmically overproduced fusion proteins and the in vitro processing of fusions with IgA protease (Igase). The significant features directing the high expression rate of pEV41-based gene fusions in Escherichia coli are the lambda pL promoter for temperature-regulated transcription and the translation initiation region of the bacteriophage MS2 polymerase gene including a downstream box (db) within the first few codons of the open reading frame. Fusion proteins generated with this system contain a short N-terminal carrier peptide allowing convenient affinity purification by means of the His6 peptide. As exemplified by the production of the variable heavy (VH) and light (VL)-chain domains of a monoclonal antibody, the fusion proteins can be specifically processed with Igase either in purified form or simply by incubation with the culture medium of recombinant E. coli [pJP10] cells. Chemical cross-linking of processed VH and VL domains resulted in a recombinant antibody Fv fragment that can specifically bind to its antigen. PMID- 8344519 TI - Construction of new Campylobacter cloning vectors and a new mutational cat cassette. AB - We have developed new Campylobacter shuttle vectors which are 6.5-6.8-kb plasmids carrying Campylobacter and Escherichia coli replicons, a multiple cloning site (MCS), the lacZ alpha gene, oriT and either a kanamycin or chloramphenicol resistance-encoding gene (KmR or CmR) from Campylobacter which functions in both hosts. These vectors can be mobilized efficiently from E. coli into C. jejuni or C. coli, and stably maintained in these hosts. Plasmids pRY107 and pRY108 carry a KmR marker and 17 unique cloning sites in two different orientations in lacZ alpha, allowing easy blue/white color selection. Plasmids pRY111 and pRY112 contain a CmR gene and 17 unique sites in both orientations. In addition, MCS are flanked by T7 and T3 late promoters and M13 forward and reverse primer sites, facilitating expression in T7 or T3 expression systems and sequence analysis. A Campylobacter CmR gene cartridge, bracketed by six restriction sites, has been developed for use in site-specific mutagenesis of Campylobacter genes. PMID- 8344520 TI - Chloroperoxidase-encoding gene from Pseudomonas pyrrocinia: sequence, expression in heterologous hosts, and purification of the enzyme. AB - The nucleotide sequence of a 1.5-kb fragment of Pseudomonas pyrrocinia DNA containing the chloroperoxidase(CPO)-encoding gene (cpo) and its flanking regions was determined. The cpo codes for a protein of 278 amino acids (aa). The mature enzyme contains no N-terminal methionine, so that the CPO monomer consists of 277 aa with a calculated M(r) of 30,304. Expression studies showed that the cpo from P. pyrrocinia is functionally expressed in Escherichia coli and Streptomyces lividans. Based on the overproduction of the CPO in E. coli, a novel and simple purification procedure was developed allowing the isolation of about 800-fold more CPO per gram of cells than was originally isolated from P. pyrrocinia. Comparison with the aa sequence of the bromoperoxidase BPO-A2 from S. aureofaciens ATCC10762 revealed an identity of 38%. PMID- 8344521 TI - Cloning and expression of a Pseudomonas 3 alpha-hydroxysteroid dehydrogenase encoding gene in Escherichia coli. AB - A bacterial strain, B-0831, which produced 3 alpha-hydroxysteroid dehydrogenase (3 alpha HSD) was isolated and identified as belonging to the genus, Pseudomonas. Molecular weights of the purified 3 alpha HSD, determined by SDS-PAGE and by chromatography on Sephacryl S-200, were about 25 and 50 kDa, respectively. A genomic library of Pseudomonas sp. B-0831, prepared in the plasmid vector pACYC184, was screened with probes based on the amino acid (aa) sequence of the protein to obtain the plasmid, p3 alpha HSD1, identified by hybridization with the probes, that contained a 2.4-kb insert from Pseudomonas DNA. When the 1.4-kb SphI fragment of p3 alpha HSD1 was inserted into the vector, pUC118, and introduced into Escherichia coli DH1 under the control of lacZ promoter in the vector, the transformants produced 200-fold more 3 alpha HSD intracellularly than Pseudomonas sp. B-0831. Sequence analysis of the 3 alpha HSD gene revealed that an ORF encoding 3 alpha HSD consists of 254 aa, with a calculated M(r) of 25,761, suggesting that the enzyme consists of homodimer subunits. PMID- 8344522 TI - Cloning and sequencing of the dnaK region of Streptomyces coelicolor A3(2). AB - The dnaK homologue of Streptomyces coelicolor A3(2) strain M145 has been cloned and sequenced. Nucleotide sequence analysis of a 2.5-kb region revealed an open reading frame (ORF) encoding a predicted DnaK protein of 618 amino acids (M(r) = 66,274). The dnaK coding sequence displays extreme codon bias and shows a strong preference for CGY and GGY, for Arg and Gly codons, respectively. The predicted DnaK sequence has a high Lys:Arg ratio which is not typical of streptomycete proteins. The region immediately downstream from dnaK contains an ORF for a GrpE like protein; the predicted start codon of grpE overlaps the last two codons of dnaK, indicating that the two genes are translationally coupled. This organisation differs from that reported for other prokaryotes. PMID- 8344524 TI - Construction of new T vectors for direct cloning of PCR products. AB - More than half of the products of PCR contain an extra A residue at the 3' end, which is the result of the template-independent activity of Taq polymerase. To facilitate cloning of the products of PCR without modification, T vectors, which have a single overhanging T residue at the 3' end, have been developed. In the present study, we constructed new T vectors which can be prepared in the laboratory by simple digestion with the restriction enzymes AspEI or Eam1 105I. PMID- 8344523 TI - Construction and characterization of a novel cross-regulation system for regulating cloned gene expression in Escherichia coli. AB - A novel cross-regulation system employing two pairs of interacting promoter repressor systems was constructed using the tac-lacI and lambda pL-cI promoter operator-repressor systems. In particular, transcription of the cat gene and the fused cI gene is regulated by the tac promoter, while transcription of the lacI gene is controlled by the lambda pL promoter. In order to compare CAT production from this new system with a currently employed transcription control configuration, a control expression vector utilizing the constitutive repressor synthesis configuration was also constructed. In this construct, cat is under the control of the tac promoter, and lac repressor is provided from a single copy of the lacIq allele included in the plasmid. Induction results using different copy number vectors indicate that induced cat expression levels are at least twofold higher using the cross-regulation system which has very low basal expression. These results match well with previous mathematical modeling predictions indicating excellent control of basal expression and also higher cloned-gene expression post-induction over a broad range of copy numbers for a cross regulation control configuration. Induction of the cross-regulation system both up-regulated the activation pathway and down-regulated the inhibition pathway, shifting the system steady-state from lac repressor expression to cat and cI expression. The control strategy presented here should be equally applicable to regulate transcription in diverse hosts. PMID- 8344525 TI - Sequence of the Escherichia coli K-12 edd and eda genes of the Entner-Doudoroff pathway. AB - A 3.5-kb DNA fragment from the Clarke and Carbon Escherichia coli genomic clone, pLC37-44, was sequenced on both strands. Part of the zwf gene, encoding glucose-6 phosphate dehydrogenase, and all of the edd and eda genes, encoding 6 phosphogluconate dehydratase and 2-keto-3-deoxy-6-phosphogluconate aldolase, respectively, of the Entner-Doudoroff pathway, were identified. These data are compared with those of Egan et al. [J. Bacteriol. 174 (1992) 4638-4646] and important differences were noted. PMID- 8344526 TI - The Pseudomonas putida ML2 plasmid-encoded genes for benzene dioxygenase are unusual in codon usage and low in G+C content. AB - Benzene dioxygenase, catalyzing the oxidation of benzene to cis-1,2-dihydroxy cyclohexa-3,5-diene, comprises four polypeptides that are encoded by plasmid pHMT112 of Pseudomonas putida ML2. In this study, the nucleotide (nt) sequences of four genes encoding this enzyme (bedC1C2BA) were determined, and the amino acid (aa) sequences were deduced. The sequence showed significant homology with the chromosomally encoded benzene dioxygenase and toluene dioxygenase genes (73 77% for nt and 83-99% for aa), but not the plasmid-encoded naphthalene dioxygenase genes (20-26% for nt and 32-36% for aa). A conserved motif (Cys-Xaa His-15-to-17 aa-Cys-Xaa2-His, where Xaa is any aa), proposed to bind the Rieske type [2Fe-2S] cluster, was identified in the deduced aa sequence of the iron sulfur proteins. Three regions were also identified in the flavoprotein which are likely to be involved in FAD and NAD+ binding. The gene order of bedC1C2BA is consistent with most ring-hydroxylating dioxygenases isolated from Pseudomonas. However, the G+C content of 47% is in contrast to the high G+C content of the Pseudomonas chromosome (63%) and other Pseudomonas plasmids (57%), and with its unique codon usage preference this suggests that bedC1C2BA originated from a host derived from a different genus. PMID- 8344527 TI - Genetic analysis of a Pseudomonas locus encoding a pathway for biphenyl/polychlorinated biphenyl degradation. AB - The cistronic organization of the bph locus, encoding a biphenyl/polychlorinated biphenyl (PCB) degradation pathway in Pseudomonas sp. LB400, has been elucidated. Seven structural genes, encoding biphenyl dioxygenase (bphA1A2A3A4), biphenyl-2,3 dihydrodiol-2,3-dehydrogenase (bphB), biphenyl-2,3-diol-1,2-dioxygenase (bphC) and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (bphD), have been located. The complete sequences of bphB, bphC and bphD are reported. Taken together with the data of Erickson and Mondello [J. Bacteriol. 174 (1992) 2903 2912], Pseudomonas sp. LB400 is now the first strain for which the sequences of all genes encoding the catabolism from biphenyls to benzoates have been determined. Comparisons of the deduced amino acid (aa) sequences of BphB, BphC and BphD with those of related proteins led to predictions about catalytically important aa residues. Six Bph have been detected and identified. Five of them could be obtained as the most abundant proteins when their genes were expressed in Escherichia coli. PMID- 8344528 TI - Cloning and sequence analysis of a hemolysin-encoding gene from Pseudomonas paucimobilis. AB - We report the cloning, expression and nucleotide (nt) sequence of a beta hemolysin-encoding gene, termed hlyA, from Pseudomonas paucimobilis. A genomic DNA library of the pseudomonad was constructed in Escherichia coli using the plasmid vector, pUC19. The hlyA gene was cloned by screening for a beta-hemolytic phenotype in E. coli transformants and was mapped to a 1100-bp PstI-SmaI fragment. The nt sequence analysis of the 1100-bp insert revealed a 789-bp open reading frame which is preceded by a 10-nt purine-rich sequence with a possible ribosome-binding site of GGA. The ORF terminates with a single UGA stop codon and is immediately followed by a large inverted repeat with 27-bp arms which may serve as a Rho-factor-independent transcriptional terminator. The hlyA gene codes for a protein of 263 amino acids (aa) residues with a deduced relative molecular mass (M(r)) of 29,695 and a predicted pI value of 11.5. Expression of hlyA from recombinant DNA in E. coli occurred regardless of insert orientation in the vector and produced a 29-kDa protein. Confirmation of P. paucimobilis as the source of the cloned hlyA gene was determined by DNA hybridization. A search of various nt and aa sequence databases revealed no homologues to hlyA or its encoded protein. PMID- 8344529 TI - A Bacillus subtilis large ORF coding for a polypeptide highly similar to polyketide synthases. AB - The nucleotide (nt) sequence of 13.6 kb of the outG locus of Bacillus subtilis, which maps at approximately 155 degrees between the genetic markers nrdA and polC, was determined. One putative coding sequence was identified corresponding to a large polypeptide of 4427 amino acids (aa). Structural organization at the nt and aa sequence level and extensive similarities of the deduced product, especially to EryA, suggest that the locus is potentially responsible for the synthesis of a polyketide molecule. The locus has been renamed pksX. Comparison of the deduced product with known fatty acid and polyketide synthases (PKS) suggested the presence of beta-ketosynthase, dehydratase, beta-ketoreductase and acyl-carrier protein domains. Preliminary data obtained with deletion mutants indicate that pksX is not an essential gene. PMID- 8344530 TI - Cloning and characterization of Neisseria meningitidis genes encoding the transferrin-binding proteins Tbp1 and Tbp2. AB - Genes tbp1 and tbp2, encoding the transferrin-binding proteins Tbp1 and Tbp2, have been isolated from two strains of Neisseria meningitidis. The tbp2 and tbp1 open reading frames are tandemly arranged in the genome with an 87-bp intergenic region, and the DNA region upstream from the tbp2-coding sequence contains domains homologous to Escherichia coli promoter consensus motives. Nucleotide sequence analysis suggests the existence of a Tbp1 precursor carrying an N terminal signal peptide with a peptidase I cleavage site and of a Tbp2 precursor with N-terminal homology to lipoproteins, including a peptidase II cleavage site. Comparison of the Tbp1 deduced amino acid (aa) sequences from both strains showed about 76% aa homology, while those of Tbp2 revealed only about 47% aa homology. These comparisons should be extended to other Neisseria strains in order to evaluate further this genetic divergence further. PMID- 8344531 TI - Characterization of allelic replacement in Streptococcus parasanguis: transformation and homologous recombination in a 'nontransformable' streptococcus. AB - We have obtained transformants of Streptococcus parasanguis FW213 containing allelic replacements in several chromosomal loci. Transformation occurred following electroporation with nonreplicating plasmids carrying two antibiotic resistance-encoding genes, one of which is inserted into DNA homologous to the chromosomal target. In contrast with other streptococci, S. parasanguis FW213 is not transformed by linear DNA. Mutations in nonreplicating plasmid DNA preferentially replaced their homologues in the S. parasanguis FW213 chromosome by a double-crossover homologous recombination event, as shown by the fact that over 90% of transformants were sensitive to the vector-coded antibiotic marker. Southern blot analysis of these transformants showed that three of the five target loci had been mutated, and that the wild-type sequence had been replaced by the mutated sequence carried on the transforming plasmid. This bias toward homologous replacement rather than integration of the entire transforming plasmid DNA simplifies site-specific mutagenesis and genetic analysis of the streptococcal chromosome. PMID- 8344532 TI - Histidine-tagged RNA polymerase: dissection of the transcription cycle using immobilized enzyme. AB - A stretch of six histidine residues (His6) has been genetically fused to the C terminus of the beta' polypeptide of Escherichia coli RNA polymerase. The His6 tagged beta' subunit assembles into RNA polymerase molecules which perform all vital in vivo functions and behave qualitatively normally in vitro. The His6 tag permits rapid purification of the enzyme directly from crude cell extracts or from an in vitro reconstitution reaction by adsorption to Ni(2+)-chelating agarose resin, followed by elution with imidazole. The enzyme bound to the matrix remains transcriptionally active. The immobilized enzyme can withstand repeated buffer changes without substantial activity loss and permits controlled stepwise 'walking' of the transcriptional complex along the DNA template, and isolation of defined intermediates in the transcription cycle. The immobilized RNA polymerase provides a powerful experimental system for structural and functional analysis of RNA polymerase and its interaction with regulatory factors. PMID- 8344534 TI - [Atmospheric air pollution of Moscow]. PMID- 8344535 TI - [ Hygienic prognosis of air pollution caused by Kansko-Achinsk thermoelectric power plant emission]. PMID- 8344533 TI - Sequence of a staphylococcal gene, vat, encoding an acetyltransferase inactivating the A-type compounds of virginiamycin-like antibiotics. AB - The Staphylococcus aureus plasmids, pIP680 and pIP1156, which confer resistance to A-type compounds of virginiamycin-like antibiotics (Vml: streptogramin A, pristinamycin IIA, virginiamycin M) and to synergistic mixtures of the A and B compounds of Vml antibiotics, were shown to direct the modification of A-type compounds by acetylation. The vat gene, encoding the acetyltransferase modifying A-type compounds, was isolated from plasmid pIP680 and sequenced. This gene potentially encodes a 219-amino-acid (aa) protein, VAT, of 24 330 Da showing at least 38% aa identity with two chloramphenicol acetyltransferases encoded by cat genes isolated from Escherichia coli and Agrobacterium tumefaciens. Resistance to A-type compounds of Vml antibiotics conferred to S. aureus by vat was not expressed in E. coli, although a protein having a M(r) similar to that encoded by this gene was detected in E. coli minicells. The vat gene was detected by the polymerase chain reaction in two chromosomally located staphylococcal conjugative elements and in the conjugative plasmid, pIP1156, conferring resistance to A-type compounds. PMID- 8344536 TI - [Evaluation of maximum permissible concentration of melamine in the atmospheric air]. PMID- 8344537 TI - [Hygienic assessment of the waste water disposal in electroplating production]. PMID- 8344538 TI - [Effectiveness of an electrolysis unit for decontamination of biologically purified sewage waters]. PMID- 8344539 TI - [Hygienic characteristics of the fibrous basalt soil substitutes]. PMID- 8344540 TI - [Prognosis of development of cardiovascular diseases in managers]. PMID- 8344541 TI - [Chemiluminescent study of the oxidative metabolism of leukocytes in dust induced respiratory diseases ]. PMID- 8344542 TI - [Hygienic evaluation of workplace conditions at the thermoelectric power station in hot climate]. PMID- 8344543 TI - [Experimental study on maximum allowable concentration of calcium carboxymethylcellulose in the air of the working area]. PMID- 8344545 TI - [Results of experimental introduction of interregional standards for the assessment of physical development in children]. PMID- 8344544 TI - [Physical work capacity of school children of different age, sex, and somatic development]. PMID- 8344546 TI - [Physical development and health status of pre-school children in Orel]. PMID- 8344547 TI - [Adaptation of the hypothalamo-hypophyseal-adrenal cortex system in children in various air pollution conditions]. PMID- 8344548 TI - [Rationale for the comprehensive sanitary and ecologic index of the quality of urban residential section]. PMID- 8344549 TI - [Ecologic and hygienic problems of environmental pollution by polychlorinated bicyclic aromatic hydrocarbons]. PMID- 8344550 TI - [Physiologic standards of the parameters of peripheral blood and thermoregulation in laboratory animals]. PMID- 8344551 TI - [Ozone in the atmospheric air of Havana]. PMID- 8344552 TI - [History of the development of national hygiene of children and adolescents]. PMID- 8344553 TI - [Methods of improvement of postgraduate training of public health physicians in the field of Soviet legislation]. PMID- 8344554 TI - [Educational measurement of hygienic instruction and education of designated population groups]. PMID- 8344555 TI - [History of development of the community hygiene department of the Leningrad medical institute of sanitation and hygiene]. PMID- 8344556 TI - [Present problems of water supply and sanitary protection of reservoirs]. PMID- 8344557 TI - [History of teaching hygiene at the medical school of Moscow university]. PMID- 8344558 TI - [History of community hygiene in the USSR]. PMID- 8344559 TI - [Experience in constructing quizes on environmental protection]. PMID- 8344560 TI - [Gas-chromatographic determination of triadimenol in the environment and biological materials]. PMID- 8344561 TI - [Analysis of formaldehyde in the water and in model systems]. PMID- 8344562 TI - [Some problems of toxicology in the assessment of low intensity factors]. PMID- 8344563 TI - [Stereometry in the evaluation of pesticide action on the gastric mucosa]. PMID- 8344564 TI - [Mathematical and statistical aspects of the pupillometric information in the screening diagnosis systems]. PMID- 8344565 TI - [Evaluation of epichlorohydrin in biologic media by vapor-phase gas chromatography]. PMID- 8344566 TI - [Prognosis of risk from new pesticides for man]. PMID- 8344567 TI - [The adaptive principle in radiation hygiene]. PMID- 8344568 TI - [Research development of problem "Scientific principles of hygiene and physiology of human adaptation to conditions of the World's ocean"]. AB - Work of problem-solving commission on "Scientific background of hygiene and physiology of human adaptation to World ocean conditions" is described. Medical problems of the water transport as key problems are noted. PMID- 8344569 TI - Painful rib syndrome--a review of 76 cases. AB - The painful rib syndrome consists of three features: pain in the lower chest or upper abdomen, a tender spot on the costal margin, and reproduction of the pain on pressing the tender spot. This is a common cause for referral to a general medical/gastroenterology clinic, accounting for 3% of new referrals in Lincoln. Seventy six consecutive patients were studied. The mean age was 48 years and 70% were women. Forty three per cent had been investigated, often extensively, before referral, and eight had had a non-curative cholecystectomy. The case notes from all patients were reviewed and a follow up questionnaire was sent after a mean period of four years to those 72 still alive, of which 56 replied. Thirty nine (70%) still had the pain although all except three had learnt to live with it. Despite a firm diagnosis being given, 25 (33%) patients were referred again to hospital by their general practitioner. All further investigations were negative apart from the finding of gall stones in three patients. The four patients who died had died from unrelated causes. The painful rib syndrome is common but underdiagnosed. It is a safe, clinical diagnosis requiring no investigation. Systematic firm palpation of the costal margin in recommended in all patients presenting with pain in the lower chest or upper abdomen. PMID- 8344570 TI - Inflammatory bowel disease--a radical view. PMID- 8344571 TI - Crohn's disease: the genetic contribution. PMID- 8344572 TI - Measurement of bicarbonate output from the intact human oesophagus. AB - Injury of the oesophageal mucosa can result from exposure to refluxed gastric acid and pepsin. Competence of the lower oesophageal sphincter and peristaltic activity serve to reduce contract time between luminal acid and oesophageal mucosa, but intraluminal neutralisation of residual acid by bicarbonate may also be important in preventing oesophageal mucosal injury. Whereas swallowed saliva contains bicarbonate, recent experiments have also demonstrated alkali secretion from the mammalian oesophagus. Bicarbonate secretion from the human oesophagus was therefore examined with an intubation technique and perfusion of the oesophagus with a non-absorbable marker. Saliva, gastric, and oesophageal aspirates were collected and bicarbonate concentrations determined by measurements of pH and pCO2 or by back titration. In 32 normal subjects (17 women, 15 men) median basal oesophageal bicarbonate secretion determined by a pH/pCO2 method was 416 (range 139-1050) mumol/hour/10 cm. In a subgroup of 15 experiments median oesophageal bicarbonate output was 489 (range 157-1033) mumol/hour/10 cm (pH/pCO2 method) compared with a median alkali output of 563 (range 135-799) mumol/hour/10 cm as determined by back titration. The difference was not significant. Salivary contamination of the oesophagus accounted for 25% of all bicarbonate measured within the oesophagus and refluxed gastric bicarbonate accounted for 2.5%. Bicarbonate secretion from the normal human oesophagus may, in combination with swallowed salivary bicarbonate, play a part in preventing oesophageal mucosal damage due to refluxed gastric acid and pepsin. PMID- 8344573 TI - Fibroblast growth factor in gastroprotection and ulcer healing: interaction with sucralfate. AB - The study was designed to determine the gastroprotective and ulcer healing efficacy of basic transforming growth factor (bFGF) and to assess whether this peptide contributes to the action of sucralfate on the rat stomach. Application of human recombinant bFGF (1-100 micrograms/kg/hour subcutaneously) failed to affect the formation of acute gastric lesions induced by 100% ethanol and acidified aspirin but reduced the stress induced by gastric lesions. Sucralfate (100-200 mg/kg given orally) protected gastric mucosa against the ethanol, aspirin, and stress induced acute gastric lesions but the addition of bFGF (100 micrograms/kg subcutaneously or intragastrically) failed to affect sucralfate induced protection against ethanol or aspirin but increased that against stress. Administration of bFGF (3-300 micrograms/kg/day) by an intragastric or an intraperitoneal route or sucralfate (400 mg/kg/day) orally to rats with acetic acid induced gastric ulcers, enhanced the healing rate of these ulcers during seven day treatment in a dose dependent manner. This was accompanied by a pronounced increase in the number of capillaries and myofibroblasts and in DNA synthesis and DNA and RNA concentrations in the granulation tissue in the ulcer area. [125I]bFGF (1 microCi) applied subcutaneously or intragastrically accumulated in two to threefold higher amounts in the ulcer area than in the intact mucosa, particularly in rats treated with sucralfate. Concurrent treatment with indomethacin (2 mg/kg intraperitoneally) delayed ulcer healing and reduced the binding of labelled bFGF to the ulcer area, angiogenesis, and DNA synthesis by sucralfate. Addition of [125I]bFGF to sucralfate at various pHs resulted in the coprecipitation of bFGF by sucralfate in a pH dependent manner from about 10% at pH 7.0 to 90% at pH 1.5. Thus bFGF shows little protective activity and is not essential for gastroprotection afforded by sucralfate but plays an important part in healing of gastric ulcers possibly due to its growth promoting and angiogenic actions. PMID- 8344574 TI - Acid secretion and sensitivity to gastrin in patients with duodenal ulcer: effect of eradication of Helicobacter pylori. AB - The effect of ulcer healing with eradication of Helicobacter pylori (H pylori) on gastric function was investigated in nine patients with duodenal ulcer disease. One month after eradication there were significant reductions in both basal plasma gastrin concentration, from a median (range) of 19 (1-22) to 6 (2-15) pmol/l (p < 0.05), and of basal acid secretion from 8.3 (2.4-24) to 2.6 (1.4-8.1) mM H+/h, (p < 0.01). The peak acid secretion rate was unchanged from 37 (16-59) to 37 (21-59) mM H+/h. After treatment there was no change in the parietal cell sensitivity to stepped infusions of gastrin heptadecapeptide: the median concentration of gastrin required for 50% of maximal acid secretion (EC50) was 41 (14.8-126) before and 33 (23-125) pmol/l after eradication of H pylori. The metabolic clearance rate of gastrin was also unaffected by the eradication of H pylori. Thus eradication of H pylori infection from patients with active duodenal ulcers is accompanied by falls in both basal gastrin release and basal acid secretion without a change in the parietal cell sensitivity to gastrin. Cyclical changes in H pylori infection may cause the variations in basal acid secretion that are seen in duodenal ulcer disease. PMID- 8344575 TI - Study of the proliferation in human gastric mucosa after in vivo bromodeoxyuridine labelling. AB - Studies to measure human gastric crypt or gland cell proliferation may have a number of practical clinical applications in relation to both benign and malignant gastric conditions. Bromodeoxyuridine (BrdUrd) labels human gastric mucosal cells in the S phase. Computer aided data analysis of labelled mucosa allows static proliferative indices to be estimated, including the crypt labelling index (LI), the peak labelling position, the distribution of labelled cells and indirectly the crypt growth fraction. Multiparameter flow cytometric analysis of labelled nuclei allows the S phase duration (Ts) of mucosal cells to be estimated. Specimens of histologically normal gastric body (GB, n = 16) and antral mucosa (GA, n = 10) were obtained from 25 patients with gastric carcinomas who received a bolus dose of 250 mg BrdUrd between 3.0 and 15.7 hours before surgery. Tissue sections were stained by an immunohistochemical method and subjected to detailed counting of up to 50 longitudinal crypts per specimen. The total crypt labelling index was calculated by a grid counting method. A significant difference existed between the proliferative compartments of gastric antral and body mucosa measured by a number of criteria. The median lengths of the crypts were 137 cells (GB) and 188 cells (GA). The median peak labelling positions were cell 26 (GB) and cell 61 (GA) from the crypt orifice. The mean crypt labelling indices were 2.8% (GB) and 4.8% (GA). The mean Ts of GA cells was 7.7 hours and of GB cells was 10.8 hours. PMID- 8344576 TI - Ablation of capsaicin sensitive afferent nerves impairs defence but not rapid repair of rat gastric mucosa. AB - Capsaicin sensitive afferent neurones have previously been reported to play a part in gastric mucosal protection. The aim of this study was to investigate whether these nociceptive neurones strengthen mucosal defence against injury or promote rapid repair of the damaged mucosa, or both. This hypothesis was examined in anaesthetised rats whose stomachs were perfused with ethanol (25 or 50% in saline, wt/wt) for 30 minutes. The gastric mucosa was inspected 0 and 180 minutes after ethanol had been given at the macroscopic, light, and scanning electron microscopic level. Rapid repair of the ethanol injured gastric mucosa (reduction of deep injury, partial re-epithelialisation of the denuded surface) took place in rats anaesthetised with phenobarbital, but not in those anaesthetised with urethane. Afferent nerve ablation as a result of treating rats with a neurotoxic dose of capsaicin before the experiment significantly aggravated ethanol induced damage as shown by an increase in the area and depth of mucosal erosions. Rapid repair of the injured mucosa, however, as seen in rats anesthetised with phenobarbital 180 minutes after ethanol was given, was similar in capsaicin and vehicle pretreated animals. Ablation of capsaicin sensitive afferent neurones was verified by a depletion of calcitonin gene related peptide from the gastric corpus wall. These findings indicate that nociceptive neurones control mechanisms of defence against acute injury but are not required for rapid repair of injured mucosa. PMID- 8344577 TI - Effect of gastro-oesophageal reflux on upper oesophageal sphincter motility in children. AB - Motor events of the upper oesophageal sphincter associated with gastro oesophageal reflux were evaluated in 53 symptomatic children (median age 13 months) who were studied recumbent and unsedated. Children were divided into four groups according to symptoms, and then into two groups according to the presence or absence of neurological deficit. No grouping had basal upper oesophageal sphincter pressure that differed significantly from any other. Oesophageal distention due to gastro-oesophageal reflux, which was recognisable as oesophageal common cavity episodes, was associated with augmentation of mean basal upper oesophageal sphincter pressure from 36.5 (SD 18) mm Hg to 48.5 (18) mm Hg (p < 0.0001), irrespective of whether gastro-oesophageal reflux caused oesophageal acidification. Abrupt relaxations of the upper oesophageal sphincter independent of swallowing and lasting up to three seconds occurred during 54% of common cavity episodes. Forty nine per cent of these relaxations occurred within four seconds after the onset of distention. The oesophageal distention caused by gastro-oesophageal reflux is a potent stimulus of transient upper oesophageal sphincter relaxations in children. These relaxations are a more likely explanation for oesophagopharyngeal reflux than defective basal upper oesophageal sphincter tone. PMID- 8344578 TI - Isotope gastric emptying tests in clinical practice: expectation, outcome, and utility. AB - Tests of gastric emptying with modern scintigraphic methods are recommended in the clinical management of gastric disorders. An audit of 472 gastric emptying tests carried out over a 10 year period was performed to discover the reasons for requests from consultant clinicians, their anticipation of the results of tests, and the influence of the results upon the subsequent management of their patients. Excluding control (n = 47) and research (n = 50) studies, there were 375 clinical referrals that could be grouped under the headings: non-ulcer dyspepsia (n = 72), suspected diabetic gastroparesis (n = 18), peptic ulcer (n = 15), suspected delayed gastric emptying after surgery (n = 154), dumping and diarrhoea (= 107), and other indications (n = 9). Although the results were abnormal for 55 (48%) of the 'medical' patients, they did not seem to influence clinical management. Delayed gastric emptying after surgery was confirmed in only 20% of patients referred with this clinical diagnosis. Conversely, most (79%) o the patients referred with dumping and diarrhoea exhibited abnormally rapid emptying. Isotope gastric emptying studies may be useful in clinical practice. The results are often at variance with the clinical diagnosis. Clinicians must take into account the nature of the test meal used when results are correlated with clinical features. PMID- 8344579 TI - Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea. AB - Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5 193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1 174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS. PMID- 8344580 TI - Glycosylation and sulphation of colonic mucus glycoproteins in patients with ulcerative colitis and in healthy subjects. AB - Studies have been made of mucus glycoprotein biosynthesis in different regions of the lower gastrointestinal tract in normal patients and those with ulcerative colitis (UC), active or inactive, by means of 3H-glucosamine (3H-GlcNH2)--35S sulphate double labelling of epithelial biopsy specimens under culture conditions. The time based rate of 3H-GlcNH2 labelling of mucus in rectal tissue was similar to that in active or inactive UC whereas the rate of 35SO4(2) labelling was significantly increased in active disease. The 3H specific activities measuring the amount of isotopic incorporation into surface and tissue mucus glycoproteins were increased in patients with active UC compared with normal or inactive subjects. The 35S specific activities did not differ significantly between patients with active UC and those in remission. In the rectum, glycosylation of mucus glycoproteins decreases with the increasing age of the patient. Regional differences in 3H-labelling of mucus components are reported for ascending colon, transverse colon, sigmoid colon, and rectum. Sulphation (35S-labelling) was higher in all parts of the colon in left sided UC. Results point to accelerated glycosylation of core proteins in the active phase of UC. PMID- 8344581 TI - Serum carnitine concentrations in coeliac disease. AB - Carnitine is essential for muscle energy production and is required for the transport of long chain fatty acids and acyl co-enzyme A derivatives across the inner mitochondrial membrane. Recently, an absorptive transport mechanism was discovered at the small bowel level suggesting the possibility of a carnitine deficient state in patients with mucosal damage. Therefore, this study investigated carnitine concentrations in serum of patients with coeliac disease. Serum samples were obtained from 12 patients with active coeliac disease and seven with non-active disease, and compared with serum samples of 17 children with gastrointestinal symptoms but with a small bowel normal on biopsy examination and 33 normal controls. Total serum carnitine concentration was significantly lower in the patients with coeliac disease compared with the other two groups and to reference values. When the degree of atrophy of coeliac intestinal mucosa was numerically graded, serum carnitine concentrations did not correlate to the degree of the intestinal lesion but were significantly lower in the damaged intestine compared with the group with normal mucosa. It is suggested that coeliac disease should be considered as a potential cause of secondary carnitine deficiency. PMID- 8344583 TI - Restorative proctocolectomy with end to end pouch-anal anastomosis in patients over the age of fifty. AB - This study was to examine whether 'fit' patients over the age of 50 who require elective surgery for ulcerative colitis are suitable candidates for restorative proctocolectomy, providing that they are continent before operation and that the anal sphincter is preserved in its entirety without stripping of the mucosa or endoanal anastomosis. Between 1986 and 1991, 18 patients 50 to 66 years old (median 55 years: nine men) underwent restorative proctocolectomy with end to end ileoanal anastomosis without mucosal stripping (12 quadruplicated (W), four duplicated (J), two no reservoir). The results were compared 12 (range three to 24) months later with those of 18 matched patients who were less than 50 years of age (median 34 years). In patients over 50, median resting anal pressure was 88 (range 44-131) cm water before and 80 (47-138) cm water after the operation (NS). In patients under 50, median resting anal pressure was 76 (51-128) cm water before and 77 (36-137) cm water after operation (NS). Resting anal pressure in older patients did not differ significantly from that in younger patients either before or after the operation. Both sensory and reflex anal functions were preserved as well after operation in the older patients as in the younger ones. The clinical results in patients over 50 were slightly inferior to the results for the younger patients, but the difference was small and not significant. Hence age alone is not a contraindication to restorative surgery provided that the anal sphincter is preserved in its entirety. PMID- 8344582 TI - Growth and clinical course of children with Crohn's disease. AB - Growth impairment is a common complication of childhood Crohn's disease, but longitudinal data and follow up studies into adulthood are sparse. This study reviewed the records of 100 Tanner stages 1 and 2 children (66 males, 34 females) consecutively diagnosed with Crohn's disease at this hospital between January 1980 and June 1988. The influence of sex, anatomical location of disease, severity of symptoms, corticosteroids, and surgical intervention on growth were analysed by univariate and multivariate regression analysis. At diagnosis mean standard deviation score (SDS) for height was -1.11 (1.28) (males -1.14 (1.26), females -1.05 (1.33)). Twenty one children were below the third centile for height. During years one and two height velocity (cm/y) was 4.4 (2.3) and 5.1 (2.7), but 40% of children in year one and 33% of children in year two grew less than expected (< 4 cm). Forty nine children grew < 4 cm/y during two or more of the 4.9 (1.8) years of follow up. Severity of gastrointestinal symptoms was the major factor influencing linear growth velocity (p < 0.01 for years one and two). Despite the high prevalence of growth impairment, the subset of children who had reached maturity by the time of the study (n = 67) nevertheless maintained their height centile. The SDS for height at ultimate follow up was -0.82 (1.1). Compared with diagnosis, change in SDS was +0.35 (1.08). Growth increments were comparable for surgically treated patients v patients only treated medically and among patients stratified by location of disease. Females (n = 25) achieved greater catch up growth than males (n = 42). Ultimate SDS for height for females was -0.48 (0.91) v -1.02 (1.19) for males. Change in SDS for height was +0.66 (1.27) for females v +0.16 (0.90) for males (p=0.02). These data confirm the frequency of growth impairment in childhood Crohn's disease. After diagnosis, however, the prognosis for ultimate linear growth is good. PMID- 8344584 TI - Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps. AB - Colonic crypt cell proliferation is used as an indicator of risk of colorectal carcinoma. Subjects with adenomatous polyps and cancer have an increased cell proliferation and a shift of the proliferative zone towards the apex of the crypt. Epidemiological and in vitro studies have confirmed a link between vitamins A, E, C, beta-carotene, and colorectal cancer. In vitro bromodeoxyuridine immunohistochemical technique was used to assess the effect of daily oral supplementation with vitamin E (160 mg), vitamin C (750 mg), or beta carotene (9 mg) on the colonic crypt cell proliferation in patients with adenomatous polyps (n = 40) compared with normal subjects with no colonic disease (n = 20). The patients were given supplementation for one month and colonic biopsy specimens were taken before and at the end of the trial. Patients with adenomatous polyps had a significantly higher mean labelling index per cent than controls (p < 0.001). Vitamin C or beta-carotene supplementation, however, significantly reduced the total proliferation (p < 0.005) whereas vitamin E supplementation had no effect on the colonic crypt cell proliferation. beta carotene reduced cell proliferation at the base of the crypt only. Vitamin C reduced cell proliferation in all the crypt compartments from the apex to the base to those values seen in age and sex matched controls. These findings indicate that prolonged supplementation with vitamin C may reduce the recurrence of adenomatous polyps. PMID- 8344585 TI - Transjugular intrahepatic portasystemic stent shunting for control of acute and recurrent upper gastrointestinal haemorrhage related to portal hypertension. AB - The insertion of a transjugular intrahepatic portasystemic stent shunt (TIPSS) was evaluated in 22 patients with recurrent upper gastrointestinal haemorrhage related to portal hypertension (bleeding from oesophageal varices 10, gastric varices six, portal hypertensive gastropathy six). TIPSS was successfully performed electively in 15 patients and as an emergency in three patients. Twelve patients have had no further admissions with bleeding after TIPSS. Single episodes of bleeding were noted in six patients after TIPSS associated with shunt thrombosis (two), intimal hyperplasia within the shunt (two), and shunt migration (one). Another patient presented with reaccumulated ascites suggesting poor shunt function but died from massive variceal haemorrhage before further assessment could be performed. There was one death related to the procedure. Two patients developed encephalopathy after TIPSS, in one patient this was controlled by the insertion of a smaller diameter stent within the existing TIPSS. Several complications arose in earlier patients that have not recurred after modification of the initial technique. TIPSS can be life saving and is effective in controlling variceal haemorrhage and rebleeding from oesophageal or gastric varices and portal hypertensive gastropathy. Larger and longer term studies are required, however, to define the role of TIPSS in the overall management of such patients. PMID- 8344586 TI - Serum concentrations of laminin in cirrhosis of the liver. AB - Laminin, a glycoprotein synthesised by Ito cells, has been considered a marker of fibrogenesis. The behaviour of laminin and clinical and laboratory data in 83 patients with cirrhosis were studied to find the factors associated with increases in this glycoprotein. There were increased concentrations of laminin in 62.7% of the patients (40% of the Child's A, 64.5% of the Child's B, and 75% of the Child's C categories). Significant differences in laminin concentrations were found between the Child's grades (p = 0.009) and between patients and controls (p < 0.0001). Correlations were found between laminin concentrations and mean corpuscular volume, aspartate aminotransferase, aspartate aminotransferase: alanine aminotransferase ratio, alkaline phosphatase activity, bilirubin and glycocholic acid concentrations, and hypoalbuminaemia--that is, variables related to liver insufficiency and alcohol intake. Moreover, patients with an alcohol intake higher than 100 g/day had higher laminin concentrations than those with a lower intake (p = 0.03). Conversely, there was no significant association with portal hypertension. Multivariate analysis showed that mean corpuscular volume, bilirubin concentrations, and hypoalbuminaemia were independently associated with laminin concentrations. Poor degradation associated with liver insufficiency seems to play an important part in the increase in serum laminin concentrations in these patients. PMID- 8344587 TI - Inappropriate expression of blood group antigens on biliary and colonic epithelia in primary sclerosing cholangitis. AB - The distribution of carbohydrate antigens of the ABO, Lewis, and Kell systems was examined in biliary and colonic epithelial of 11 patients with primary sclerosing cholangitis (PSC) using a panel of 11 monoclonal antibodies. Controls consisted of 27 liver biopsy specimens (11 normal, six alcoholic liver disease, five extrahepatic obstruction, and five primary biliary cirrhosis) and 24 colonic biopsy specimens (six normal, four Crohn's disease, and 14 ulcerative colitis). There was inappropriate staining with anti-A (four of six, 66%) and anti-B (nine of 11, 81%) in biliary epithelium of PSC patients compared with normal and disease controls. Expression of Lewis antigens was increased in patients with cholestatic liver disease. Ninety one per cent of PSC patients showed a similar pattern of inappropriate staining by anti-A and anti-B antibodies in colonic epithelium compared with 33% of normal and 42% of inflammatory bowel disease controls. There is inappropriate expression of A and B carbohydrate antigens in biliary and colonic epithelium in PSC. Whether these oncofetal antigens are implicated in the pathogenesis of this condition is discussed. PMID- 8344590 TI - Isolated primary oesophageal involvement by lymphoma: a rare cause of dysphagia: two case histories and a review of other published data. AB - Primary oesophageal involvement by lymphoma in two patients, one with Hodgkin's disease and one with non-Hodgkin's lymphoma is reported. In both, there were no manifestations of the disease outside the oesophagus, which is exceptionally rare. In the patient with non-Hodgkin's lymphoma, the oesophageal tumour was the first manifestation of lymphoma. Shortly after admission he developed a tracheo oesophageal fistula from which he died before treatment could be started. In the patient with Hodgkin's disease, isolated oesophageal lymphoma was the first relapse after a 13 year interval free of disease. As he had previously received mediastinal irradiation he was treated with combination chemotherapy that resulted in long term survival (> five years). Several other long term survivors have been described but only after radiotherapy or surgery. These findings suggest that systemic chemotherapy may be equally successful in treating isolated primary oesophageal lymphoma, thus offering an alternative for those patients in whom local treatment is contraindicated. PMID- 8344589 TI - Pancreatic hypertrophy with acinar cell nodules after longterm fundectomy in the rat. AB - The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy. PMID- 8344588 TI - Complex carbohydrate malabsorption in exocrine pancreatic insufficiency. AB - The magnitude of complex carbohydrate malabsorption in exocrine pancreatic insufficiency has not been well quantified in the past. The quantity of carbohydrate malabsorbed after a rice starch (100 g) meal in 20 patients with chronic pancreatitis (n = 10) or pancreatic cancer (n = 10) was therefore estimated. Patients had a three day stool fat collection (80 g/24 hour fat intake), a lactulose (20 g), and a rice flour (100 g) breath hydrogen test. Normal controls (n = 29) had a postprandial H2 increase < or = 14 ppm and malabsorbed (mean (SEM)) 1.12 (0.44) (range 0-11.10) g of the 100 g of carbohydrate ingested. Patients malabsorbed significantly more carbohydrate (11.36 (2.23) (range 8.90-32.60) g, F1.47 = 29.92, p < 0.001). The number of patients with fat (> 7 g, n = 8) or carbohydrate (increase in H2 > or = 20 ppm, n = 10) malabsorption was not different (chi 2 = 0.10, p = 0.75). There was a significant correlation between faecal fat and amount of malabsorbed carbohydrate (r = 0.60, F1.17 = 9.70, p = 0.006) and faecal fat and stool wet weight (r = 0.57, F1.18 = 8.67, p < 0.009), but not between stool wet weight and amount of malabsorbed carbohydrate (r = 0.28, F1.17 = 1.45, p = 0.25). Although patients with exocrine pancreatic insufficiency malabsorb 10%-30% of the ingested complex carbohydrate, the main determinant of stool wet weight could be faecal fat. PMID- 8344591 TI - Myofibroblasts in hollow visceral myopathy: the origin of gastrointestinal fibrosis? AB - A patient with hollow visceral myopathy is reported in whom light microscopical studies of the small and large intestine showed typical features of degeneration, thinning, and fibrous replacement of smooth muscle of the gastrointestinal tract. Electron microscopy showed a striking increase in collagen with minimal fibroblast proliferation. Smooth muscle fibres had a range of ultrastructural abnormalities including myofilament disarray, electron lucency of the cytoplasm, and proliferation of the endoplasmic reticulum. Some fibres seemed to have typical ultrastructural characteristics of myofibroblasts, and others to be transition forms between typical smooth muscle cells and typical myofibroblasts. It seems likely that the fibrosis typical of this disorder has its origin in the transformation of smooth muscle fibres from a purely contractile to a myofibroblast collagen synthetic phenotype. PMID- 8344592 TI - Following the spirit. PMID- 8344593 TI - Applying Orem's self-care Framework. Orem's framework encourages nurses to always keep the client's independence in mind. PMID- 8344594 TI - An investigation of rocking as relaxation for the elderly. Does rocking elicit in the elderly the physiologic changes of the relaxation response? PMID- 8344595 TI - Over-the-counter drug use by the rural elderly. PMID- 8344596 TI - What to negotiate before accepting a DON position. PMID- 8344597 TI - Caring for caregivers: a nursing role in a corporate setting. PMID- 8344598 TI - Preventing falls in the elderly: interviewing patients who have fallen. Researchers attempt to identify fall-risk factors from the patients' point of view. PMID- 8344599 TI - Foot care protocol for the older client. A guide for working with clients to improve care of the feet. PMID- 8344600 TI - A gerontologic nurse practitioner in every nursing home: a necessary expenditure. PMID- 8344601 TI - Playing it safe with food. PMID- 8344602 TI - Congestive heart failure: old and new drugs. PMID- 8344603 TI - [Prognosis of acute myocardial infarction in the elderly. SPRINT Study Group]. AB - In countries with aging populations acute myocardial infarction (MI) in the elderly is increasing rapidly and hospital and long-term mortality remain high. During 1981-83, 5839 consecutive patients with acute MI were hospitalized in 13 coronary care units in Israel. Of these, 653 (11%) were older than 75 years, 41% were women, and 70% had a first MI. The hospital mortality in these very elderly patients was 35%. The mortality rates 1 and 5 years postdischarge were 24% and 55%, respectively. In view of this high risk and the promising results obtained elsewhere with thrombolysis, particularly in the elderly, this treatment should be routinely considered in elderly patients with acute MI when there are no specific contraindications. PMID- 8344604 TI - [Hemizona assay for evaluating fertilizing capacity of human spermatozoa]. AB - The hemizona assay (HZA), which tests the binding capacity of human spermatozoa to the zona pellucida, is described. This assay has very high sensitivity (86 100%) in predicting fertilizing capacity in the in vitro fertilization (IVF) system. It is recommended that it be carried out on semen samples before entering the IVF program. In addition, it can also help evaluate unexplained infertility and assess the quality of ova. The necessity for a control fertilized sample in each HZA might complicate the assay. To simplify the test, the use of sperm from the sperm bank was investigated. It was shown that fresh and frozen-thawed sperm have the same capacity to bind to the hemizonae. Thus, frozen donor semen preserved in the sperm bank can be used for controlling the HZA. PMID- 8344605 TI - [Actinobacillus actinomycetemcomitans endocarditis]. AB - Bacterial endocarditis caused by Actinobacillus actinomycetemcomitans (AA) is an extremely rare disease. AA, a gram negative cocco-bacillus, normally resides in the oral cavity. It is involved mostly in local oral cavity infections, but severe systemic infections caused by it have been reported. We describe a 63-year old man with endocarditis caused by AA which probably originated from a dental abscess. The course of the disease was complicated by acute myocardial ischemia, apparently caused by coronary artery embolism. To enable growth of this bacterium, blood cultures should be maintained for 2-3 weeks in a CO2-rich atmosphere. PMID- 8344607 TI - [Treatment of eyelid burns and results]. AB - Eyelid burns may cause irreversible damage to the eyelids and eye globe. We review 45 patients with eyelid burns, in 8 of whom skin grafting was required due to the deepness of the burn. The results were satisfactory in all except 1, in whom 9 surgical procedures were required to give complete coverage of the cornea. During 1 procedure skin was grafted directly onto the conjunctiva. The other 36 patients were treated conservatively. PMID- 8344606 TI - [Fanconi anemia syndrome as a predisposing factor for acquired bone marrow aplasia]. AB - A 4-year old girl who received prophylactic therapy with oral cephalexin for 1 year because of a history of urinary tract infections, was referred for evaluation of short stature. On physical examination mildly dysmorphic features were observed. Blood counts disclosed pancytopenia, and bone marrow examination showed hypoplasia of all 3 cell lines. Chromosome analysis after exposure to a DNA cross-linking agent (diepoxybutane) showed a chromosomal breakage pattern consistent with Fanconi anemia. Discontinuation of cephalexin was followed by improvement in hematological values. This course of events supports the hypothesis that acquired bone marrow depression may be a manifestation of Fanconi anemia, warranting the appropriate diagnostic work up in every case of acquired bone marrow aplasia. PMID- 8344608 TI - [Malignant peritoneal mesothelioma]. AB - Public attention has recently been devoted worldwide to malignant mesotheliomas and their relation to exposure to industrial materials, especially asbestos and its products. The more common form of the disease is the pleural type, while the peritoneal variant is rare, with an estimated incidence of less than 1:1,000,000 new cases per year. In contrast to the pleural type, the relationship of malignant peritoneal mesothelioma to exposure to asbestos is unclear. The differential diagnosis, based on clinical appearance and imaging techniques, is broad and the diagnosis is inconclusive, so that the diagnosis must be confirmed by histologic examination. Treatment is a combination of surgery, chemotherapy and irradiation. Contrary to occasional reports, the malignancy is fatal, death occurring within a few months of diagnosis. We present a 65-year-old man in whom malignant peritoneal mesothelioma was diagnosed. The presenting symptoms were a large abdominal mass involving the colon, and ascites. He died 5 months after the diagnosis was made. PMID- 8344609 TI - [Pyridoxine for severe metabolic acidosis and seizures due to isoniazid overdose]. AB - A 15-year-old girl took 3 g of isoniazid (15 tablets) in a suicide attempt and was brought unconscious to the emergency room. She was in respiratory failure, with seizures that could not be stopped with diazepam. Severe metabolic acidosis with normal serum lactate developed (pH 6.85), but did not improve after infusion of bicarbonate. Intravenous administration of pyridoxine led to prompt cessation of the seizures and to gradual improvement of acid-base status. She recovered consciousness after several hours and was discharged a week later. PMID- 8344610 TI - [Saline solution amnioinfusion--its role in modern obstetric care]. PMID- 8344612 TI - [First-aid 1993]. PMID- 8344613 TI - [Clinical guidelines. Background, methodology and significance]. PMID- 8344611 TI - [Rationing health care: ethical, medical and economic aspects]. PMID- 8344614 TI - [Results of medical licensing examinations: 1988-1991]. AB - The State of Israel Physicians' Law of 1987 requires all immigrant physicians to pass a state licensing examination in order to practice medicine. The examination is prepared by the Board of Examination for the Medical License, appointed according to the Ministry of Health regulations of 1987. It consists of 220 written multiple choice questions in internal medicine, surgery, pediatrics, psychiatry and obstetrics and gynecology. As decided by the Board of Examination, the examinations are given in Hebrew, English, Russian, Spanish, Rumanian, Bulgarian, French, Polish, Portuguese and Arabic. Physicians required to take the examination can participate in special preparatory courses given in university affiliated hospitals. The mark received at the end of the course is taken into consideration in the final grading of the candidate. Since 1988, 1,985 physicians have been examined, 89.3% of whom were immigrants from Russia and only 3% from Western countries. Of these, 1,968 (65.9%) were licensed. Factors affecting success rate were: age (mean 34 years), with the highest success rate at ages 31 35; length of medical experience, with the best results in those with 11-15 years of experience (mean 12); and country of origin, which is crucial. The success rate in immigrants from Western countries was 79.2%, from South America 72.3% and from Russia and Eastern European countries about 60%. PMID- 8344615 TI - [p53--the genome policeman]. PMID- 8344617 TI - ["Very important" patients]. PMID- 8344616 TI - [Alcohol and AIDS]. PMID- 8344618 TI - [Arrhythmias following cardiac surgery]. PMID- 8344619 TI - [Acute myocardial infarction in the elderly: prognosis and treatment]. PMID- 8344620 TI - [Fever and lymphadenopathy in a 33 year old patient with discoid lupus erythematosus]. PMID- 8344621 TI - [Involuntary outpatient commitment: ethical and legal aspects]. AB - In 1991 the Israeli Knesset (parliament) drafted new legislation for the treatment of the mentally ill. One of the innovations was involuntary outpatient commitment (IOC), which allows the district psychiatrist to order a patient to attend a clinic and receive ambulatory care. IOC is an attempt to address the problem of the "revolving door" patients, chronic mental patients who after discharge do not continue medication and therefore relapse and have to be readmitted. PMID- 8344622 TI - [Koro syndrome--clinical and cultural aspects]. AB - Koro syndrome is a triad which includes a deep-seated fear that the penis will shrink, disappear into the abdomen, and that death will follow. The patient experiences profound anxiety and performs preventive manoeuvres, such as pulling his penis outward. The disorder is considered culture-related, and is endemic in South-East Asia and China, where it occurs in epidemic and sporadic forms. Sporadic cases appear in the western hemisphere, often in association with an underlying psychiatric or organic disorder, usually of the central nervous system. 6 cases of koro have been published from Israel. PMID- 8344623 TI - [Experience with laparoscopic appendectomy]. AB - During April to August 1992, laparoscopies were performed in this department in 35 of 100 cases of appendicitis. The average patient age was 29 years; 18 of the 35 (51%) were women; 3 patients were operated on electively, and the rest as emergencies. Appendectomy was performed in 33 (94%), but not in 2 women with sepsis due to tubo-ovarian abscess; In 1 of these 2 we had to convert to laparotomy. Acute appendicitis was found in 20 (57%). In 7 women (20%) gynecologic disease was diagnosed. In 1 case (3%) a carcinoid tumor of the tip of the appendix was found and in another primary peritonitis. In the remaining 6 (17%) no lesions were found. In 33 (94%) a regular diet was resumed 25 hours postoperatively and 25 (71%) were discharged the day after operation. The only complication was an abdominal wall hematoma in a single case, which resolved spontaneously. It is our impression that laparoscopy is a useful diagnostic tool in acute appendicitis, that it is a safe route for appendectomy, and that recovery is quick with minimal complications. PMID- 8344624 TI - [Treatment of the diabetic foot by hyperbaric oxygen]. AB - Diabetic foot wounds are consequences of the neuropathy and the small and large vessel disease that complicate diabetes. At the cellular level, the result is hypoxia which impairs wound healing. Hyperbaric oxygenation (HBO) may be a useful adjuvant to wound care. It leads to enhanced oxygenation of the affected tissues, has an antiseptic effect, reduces edema, and accelerates collagen production and angiogenesis, thus enhancing tissue repair. 14 diabetics with chronic nonhealing wounds which did not respond to treatment for at least 3 months were treated by HBO. All had palpable pedal pulses. Transcutaneous measurements of tissue pO2 showed elevation from 20 +/- 10 mm Hg during air breathing to 643 +/- 242 mm Hg while breathing pure oxygen at 2.5 ATA. They were treated with HBO in 56 +/- 10 consecutive HBO sessions. In 11 there was complete wound healing, while in 1 there was partial response, in 1 minimal response, and in 1 a transient response. HBO is useful in chronic nonhealing wounds of the diabetic foot and of the diabetic foot with impending amputation. It is a safe mode of therapy, but further studies are required to establish its efficacy and to ascertain which diabetic patients and wounds will benefit the most from it. PMID- 8344625 TI - [Diazepam-induced disinhibition]. AB - Benzodiazepines are among the most often prescribed drugs worldwide, and are mostly prescribed by general practitioners and family physicians. Their side effects include tolerance, dependence, intoxication, withdrawal syndrome, retrograde amnesia, paradoxical agitation (frequent in the elderly) and disinhibition. A 32-year-old woman is presented. She was brought to the emergency room because of psychotic-like behavior. It was caused by severe disinhibition due to a single 5 mg dose of diazepam prescribed during uncomplicated bereavement. 14 hours later all symptoms had subsided and she was discharged. PMID- 8344626 TI - [Delayed pressure urticaria: therapeutic response to cetirizine]. AB - We describe a 39-year-old man who suffered from delayed pressure urticaria for 2 years. His severe symptoms did not respond to antihistamine (H1 and H2) treatment and corticosteroid therapy was given despite severe side-effects. A new, nonsedating antihistamine drug, cetirizine, relieved most of his symptoms, enabled him to be weaned from corticosteroid therapy, and restored his former quality of life. PMID- 8344628 TI - [Warm heart surgery]. PMID- 8344627 TI - [First trimester sonographic diagnosis of acrania]. AB - Anencephaly, a well-known lethal fetal malformation, was long considered to result from primary nonclosure of the neural tube. In the past few years other pathogenic mechanisms, such as reopening or degeneration of a closed neural tube have been suggested. High-resolution transvaginal ultrasonography, which provides fine visualization of the different stages in embryogenesis, allowed us to detect fetal acrania as early as the 12th week of gestation. Very high levels of alpha fetoprotein, almost undetectable levels of unconjugated estriol (E3), and postabortion histology were consistent with anencephaly, suggesting that anencephaly is the end result of fetal acrania. PMID- 8344629 TI - [Negative symptoms in schizophrenia]. PMID- 8344630 TI - [Hypertension in pregnancy--diagnostic approach and pathogenesis (Part I)]. PMID- 8344631 TI - [Pruritus in cholestatic liver diseases--still more questions than answers]. PMID- 8344632 TI - [Current management of pancreatic necrosis and infections]. PMID- 8344633 TI - [Aspects of epilepsy and psychiatry]. PMID- 8344634 TI - [Compliance with recommended periodic examinations of workers in Israel]. AB - Initial design and subsequent improvement of health education and health promotion programs should be based on reliable, current data on the health related habits of the target population. Various organizations in the Israeli health system conduct campaigns encouraging the general population to undergo periodic blood pressure and blood cholesterol measurements. In addition, regular examination of the breast and uterine cervix are recommended for women. However, there is no systematic on-going monitoring of compliance with these recommendations. Health promotion programs in the work-place are regularly conducted by the national Occupational Health Institute (affiliated with the General Labor Federation Health Insurance Institute). To obtain basic information on such health-related behavior, a survey was conducted in April 1992 in a sample of 1,042 employees at 6 places of work. The results indicate relatively low compliance with recommended periodic health examinations and demonstrate the need for regular studies of this kind in representative population samples. In this way decision-makers in public health service would be provided the data essential for determining optimal allocation of resources to health promotion programs. PMID- 8344635 TI - [Misinformation among physicians about dangers of fetal x-ray exposure]. AB - A survey among 20 gynecologists and 86 family physicians and general practitioners revealed that only 46% (70% of the gynecologists and 41% of the others) knew that exposure of a pregnant woman to common diagnostic x-ray is not an indication for therapeutic abortion (the opinion of a consensus of experts). This lack of basic information by those who advise pregnant women points to a serious public health problem. Pregnant women are frightened, and in a sense abortions are "coerced" by increasing the unwarranted anxiety. It is incumbent upon individuals and institutions to ensure that physicians, nurses and others in the health professions be well-informed and not supply misinformation. PMID- 8344636 TI - [Molecular genetics in hematology--from the laboratory bench to beside application]. PMID- 8344638 TI - [AIDS and public health law]. PMID- 8344637 TI - [The Israeli health care crisis: leadership, a cure]. PMID- 8344639 TI - [Breast milk banks--are they really necessary?]. PMID- 8344640 TI - Effects of arterial-portal glucose difference on gluconeogenesis from lactate in the isolated bivascular-perfused rat liver. AB - The effects of arterial-portal glucose difference on the gluconeogenesis from lactate were studied using the bivascular perfused liver isolated from the fasted rat. The liver was cyclically perfused at flow rates of 14 ml/min from the portal vein and of 7 ml/min from the hepatic artery with the total volume of 35 ml of perfusion medium containing 2 mM glucose, 3 mM lactate and (U-14C)-lactate for 20 min. Glucose was infused at a rate of 27.75 mumol/min into the arterial cannula (A-experiment) or the portal cannula (P-experiment), making each arterial-portal glucose gradient of +3.96 mM (arterial glucose > portal glucose) and -1.98 mM (arterial glucose < portal glucose) throughout the experiment. Perfusate lactate concentration was lower in A-experiment than in P-experiment (1.40 +/- 0.25 vs 1.93 +/- 0.23 mM at 20 min, mean +/- SD, p < 0.05). Incorporation of radioactivity from (U-14C)-lactate into glucose carbon 1 in perfusate was 5.7 +/- 0.8% of total radioactivity per 20 min in A-experiment vs 2.8 +/- 0.6%/20 min in P-experiment (p < 0.01). These results suggest that the arterial-portal glucose difference is an important factor to regulate the hepatic gluconeogenesis. PMID- 8344641 TI - Islet amyloid polypeptide/amylin contents in pancreata increase in genetically obese and diabetic mice. AB - To search for a possible relationship between islet amyloid polypeptide (IAPP)/amylin and the pathophysiology of type 2 diabetes mellitus, we examined IAPP contents in the pancreata of genetically obese and diabetic mice (C57BL/6J ob/ob and KK mice), at 24 weeks of age, using a specific radioimmunoassay. IAPP and insulin contents were noticeably increased in the ob/ob mice with marked obesity and moderate hyperglycemia. These contents slightly, but significantly increased in the KK mice with mild obesity and hyperglycemia. Thus, IAPP production is possibly influenced by factors coded by mutant genes and a possible relationship between IAPP and hyperglycemia in the strains of mice deserves further attention. PMID- 8344642 TI - The effects of growth hormone administration in vivo on skeletal muscle glutamine metabolism of the rat. AB - Human growth hormone administration to the rat for 3 or 10 days increased the concentrations of glutamine in both skeletal muscle and plasma and the rate of glutamine release was increased from muscle isolated from rats treated with growth hormone for 3 days. Growth hormone may therefore play an important role in the control of glutamine metabolism in muscle. PMID- 8344643 TI - Inhibition of progesterone action by a factor in human follicular fluid. AB - A factor was found in human follicular fluid that blocked progesterone-stimulated net uptake of 45Ca2+ in human sperm and progesterone-induced maturation of Xenopus oocyte. The factor was partially purified by ultrafiltration through PM 10 membrane and gel filtration on Sephadex G-25 column. The active fraction is effective at a concentration of 200 micrograms/ml. The present findings suggest that hFF factor may regulate the metabolism of progesterone sensitive cells. PMID- 8344644 TI - The influence of growth factors on the prostaglandin synthesis in cultured rabbit luteal cells. AB - Isolated rabbit luteal cells from day 12 of pseudopregnancy were cultured with a variety of growth factors, hCG and arachidonic acid (AA) in serum-free culture medium for 96 hours. The time course of prostaglandin (PG) E2, PGF2 alpha, and progesterone was determined. TNF-alpha, IL-2, IGF-I, IGF-II, and EGF alone were not able to change significantly the production of either progesterone or PGE2 and PGF2 alpha when compared with the controls. AA as the precursor of PG biosynthesis increased the production of PGE2 and PGF2 alpha significantly (1.2 fold and 2.6-fold, respectively; p < 0.05; p < 0.01). AA together with EGF increased the level of PG more pronounced when compared with AA alone (1.5-fold for PGE2, 5-fold for PGF2 alpha; p < 0.05 and p < 0.005). The progesterone production of the cells remained unchanged during growth factor exposure. We conclude that EGF together with high amounts of AA is able to stimulate the PG biosynthesis in cultured rabbit luteal cells. Since the level of PGF2 alpha increases more pronounced than PGE2, an activation of the PGE2 9-ketoreductase may be possible. Therefore, EGF could be relevant as an additional regression factor controlling the PGE2/PGF2 alpha-ratio in the corpus luteum of rabbits. This mechanism seems to be independent from the progesterone synthesis. PMID- 8344645 TI - Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity? AB - Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p < 0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p < 0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity. PMID- 8344646 TI - Pyridostigmine effects on TSH response to TRH in adult and children obese subjects. AB - Thyrotropin releasing hormone (TRH) administration is known to induce a greater TSH response in normal subjects than in obese subjects. In obesity even GH and PRL response to various stimuli are blunted, presumably because of an augmented somatostatinergic tone in obese subjects. Further studies have shown that pyridostigmine (Pyr), an acetylcholinesterase inhibitor, is capable of augmenting GH in obesity by means of somatostatin inhibition. In order to evaluate the possible interference of an increased somatostatinergic tone on TSH secretion, we studied the TSH response to a TRH bolus in 5 obese children with or without a pyr pretreatment. Similarly, we tested a group of 10 obese adult subjects, with TRH alone or TRH plus pyr administration, 30 min or 60 min before TRH. All subjects had a body weight of 30-50% greater than I.B.W. Our data show that a pretreatment with pyr, 60 min before TRH administration, significantly augments the TSH response in adult obese subjects but not in children; the modality of pyr administration seems to be crucial to evidenciate such an alteration since the pyr pretreatment is not effective when administered 30 min before TRH. The absence of this pyr effect in obese children induces to hypothesize that somatostatinergic tone is differentially modulated in children vs adult obese subjects. PMID- 8344647 TI - The magnitude, the kinetics and the metabolic efficiency of first-phase insulin response to intravenous glucose are related. AB - We investigated the relationship between the kinetics, the magnitude and the metabolic efficiency of first-phase insulin response (FPIR) to intravenous glucose. Twenty healthy control subjects and fifty first degree relatives of Type 1 diabetic patients were studied using a standardized protocol for the intravenous glucose tolerance test (IVGTT). The first significant increase in plasma insulin concentrations above baseline appeared as early as the 2nd min (1 min before the end of glucose injection, fast response) in 80% of controls and 70% of relatives, and at the 3rd min or later (delayed response) in the remaining subjects. The greatest delay in insulin release (5th min) was observed in 4 of 6 relatives of Type 1 diabetic patients with impaired FPIR. In the controls and the relatives, the subjects with a fast insulin response had a significantly higher FPIR (controls 215.4 +/- 93.5 vs 59.7 +/- 5.6 microU/ml, p < 0.001 and relatives 143.5 +/- 61.8 vs 55.9 +/- 27.7 microU/ml, p < 0.001) and showed better glucose assimilation (controls 3.05 +/- 1.05 vs 1.64 +/- 0.16%/min, p < 0.05 and relatives 2.6 +/- 0.96 vs 1.6 +/- 0.85%/min, p < 0.01) during IVGTT than the subjects with a delayed response. Moreover, for normal FPIR values in the group of relatives of Type 1 diabetic patients, a fast response was associated with a significantly better glucose assimilation as assessed by the incremental area under the glucose curve (358.6 +/- 64.7 vs 539.2 +/- 67.7 mmol/l per 90 min, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344649 TI - Insulin stimulates the polymorphonuclear leukocyte chemokinesis. PMID- 8344648 TI - Octreotide treatment does not improve impaired glucose uptake in cirrhosis. AB - Forearm glucose uptake during a hyperglycaemic (10 mmol/l) glucose clamp was diminished to 33% of the normal value (p = 0.012) in six cirrhotic patients compared with matched control subjects. Fasting insulin concentrations were significantly elevated in the cirrhotic patients confirming insulin resistance which may have been induced by chronic hyperinsulinaemia. The cirrhotic patients received one week of treatment with 50 micrograms octreotide subcutaneously three times daily which reduced pre-dose fasting insulin levels from 26.2 +/- 7.9 to 18.1 +/- 6.2 mU/l p < 0.005, and post dose levels to 7.0 +/- 3.5 mU/l p < 0.005. However when the glucose clamp was repeated 20 hours after the last dose of octreotide no change was detected in clamp glucose requirements, forearm glucose uptake, or stimulated insulin secretion. It was concluded that one week of lowering insulin levels does not reverse the insulin resistance of cirrhosis. PMID- 8344651 TI - Normalization of decreased plasma concentrations of growth hormone-binding protein by insulin treatment in spontaneously diabetic BB rats. PMID- 8344650 TI - Effect of macrophage colony-stimulating factor on the development of diabetes mellitus in BB rats. PMID- 8344652 TI - Effects of oestradiol-17 beta in hematological parameters and iron absorption in ovariectomized rats. PMID- 8344653 TI - The bone marrow trephine biopsy: a review of normal histology. AB - Bone marrow trephine biopsies are becoming increasingly common in routine surgical pathology. Familiarity with normal marrow histology plays an important part in understanding and interpreting marrow pathology. The aim of this article is to describe the histological features of normal human bone marrow, in particular those features which are relevant to the diagnostic pathologist. The advantages and disadvantages of different technical aspects, such as choice of embedding material and type of stain, are discussed. The use of immunochemistry in identifying different cell types within the marrow is illustrated. PMID- 8344654 TI - Lymphangiomyomatosis and angiomyolipoma: closely related entities characterized by hamartomatous proliferation of HMB-45-positive smooth muscle. AB - Angiomyolipoma is a hamartomatous condition which can occur as a component of the tuberous sclerosis complex. Lymphangiomyomatosis, another hamartomatous lesion occurring predominantly in the lungs, has long been suspected to be related to angiomyolipoma and tuberous sclerosis because of occasional clinical associations. We undertook this study to provide further support for the close relationship between these two entities. Five cases of lymphangiomyomatosis and 20 case of angiomyolipoma were retrieved for histological review and immunohistochemical studies. The antibodies used were anti-muscle specific actin (HHF-35), anti-desmin (D33) and anti-melanoma (HMB-45). Lesions featuring smooth muscle proliferation were used as controls. The proliferated smooth muscle cells in both lymphangiomyomatosis and angiomyolipoma were much plumper and paler or even clear, when compared with the deeply eosinophilic cytoplasm of the normal spindly smooth muscle cells and those of leiomyomas. Their nuclei were round to oval and pale rather than elongated and dark. Cells with bizarre nuclei were commoner in angiomyolipoma (18/20 cases) than lymphangiomyomatosis (1/5). In 12 cases of angiomyolipoma there were foci indistinguishable from lymphangiomyomatosis, i.e. plump spindle cells arranged in short fascicles around ramifying endothelium-lined spaces. All five cases of lymphangiomyomatosis stained for muscle-specific actin, desmin and HMB-45. For angiomyolipomas, the positivity rates for these markers were: 20/20, 17/20 and 18/20, respectively, including one case that was negative for both desmin and HMB-45. The various smooth muscle proliferations and tumours selected as controls were uniformly HMB 45 negative. The distinctive cytological features, morphological overlap and immunophenotypic profile all support a close relationship between lymphangiomyomatosis and angiomyolipoma, which probably represent different morphological manifestations of hamartomatous proliferation of a peculiar form of HMB-45-positive smooth muscle. PMID- 8344655 TI - Metal deposition in post-surgical granulomas of the urinary tract. AB - Fourteen cases of post-surgical granulomatous inflammation of the urinary tract were studied to investigate the possible deposition in the tissues of metals derived from the diathermy instruments used. The granulomas showed central necrosis, palisaded histiocytes and giant cells. On electronmicroscopy both amorphous material and electrondense particles were seen in the granulomas. The former appeared to be necrotic tissue. The particles were metallic in nature. Energy dispersive analysis of X-rays showed the presence of tungsten, iron, copper, nickel, chromium, zinc and vanadium. Tungsten particles were always pure. Other single particles contained two or more of the remaining elements, indicating the presence of alloy metals. Analysis of the diathermy instruments showed the cutting loops to be pure tungsten and the 'rollerballs' to be nickel silver containing copper, zinc, nickel, manganese and iron. Both the loops and balls are supported on stainless steel wires containing iron, chromium, nickel, manganese, molybdenum, copper and vanadium. It is proposed that metallic fragments from the instruments were deposited in the tissues during the surgical procedures and elicited an immunological reaction with granuloma formation. Tungsten is probably inert but nickel, chromium, copper and zinc are immunogenic. Under certain circumstances both nickel and chromium may also be carcinogenic. PMID- 8344656 TI - Expression of alpha-amylase isoenzymes and trypsin by the proliferating epithelium of large intrahepatic bile ducts and intrahepatic peribiliary glands in hepatolithiasis. AB - The expression of alpha-amylase isoenzymes (pancreatic and salivary) and trypsin by the epithelium of large intrahepatic bile ducts and peribiliary glands was examined immunohistochemically in hepatolithiasis (n = 22), extrahepatic biliary obstruction (n = 20) and normal liver (n = 22). Hepatolithiasis was associated with marked proliferation of bile duct cells and peribiliary glands. Expression of pancreatic and salivary amylase was observed in the proliferating bile duct cells and peribiliary glands of all livers, and trypsin was found in 68% of the livers. In extrahepatic biliary obstruction, proliferation of the biliary epithelium was less marked, but expression of amylase isoenzymes was observed in all livers and trypsin was found in 50%. All normal livers showed expression of amylase isoenzymes in large intrahepatic bile ducts, septal bile ducts and peribiliary glands, and trypsin was found in 73%. The density of enzyme containing acini was highest in hepatolithiasis, intermediate in extrahepatic biliary obstruction and lowest in normal liver. These results show that the proliferating biliary epithelium in hepatolithiasis contains amylase isoenzymes and trypsin and that biliary epithelium retains the ability to produce these enzymes after proliferation, suggesting that a large amount of amylase isoenzyme and trypsin may be secreted into the bile ducts in hepatolithiasis. These enzymes may play an important role in the pathophysiology of hepatolithiasis. PMID- 8344657 TI - Granulation tissue polyposis associated with carcinoid tumours of the small intestine. AB - We report two patients with ileal carcinoid tumours which were associated with polyps due to mucosal granulation tissue proliferation. In both cases the tumours had extensively infiltrated the small bowel wall and mesentery, and one had hepatic metastases. The mucosal surface of each specimen showed numerous, pale brown, sessile polyps which were restricted to the intestinal segment involved by carcinoid tumour, although not always closely related to neoplastic cells. The polyps were formed by the proliferation of capillaries, smooth muscle cells and myofibroblasts as demonstrated by immunohistochemistry and electronmicroscopy. PMID- 8344658 TI - Nodular breast lesions during pregnancy and lactation. AB - A review of the clinical and pathological features of 30 lactating nodules which were retrieved over the period 1975-1991 was undertaken. Clinically, the nodules occurred during any pregnancy and in subsequent pregnancies no further nodules developed. There were no favoured sites or lateralization of nodules, nor was there any correlation between nodule occurrence and ethnic background. Morphologically, a pre-existing underlying lesion was readily recognized in 18 cases. Seven fibroadenomas, five tubular adenomas, two of which were infarcted, and six breast hamartomas were identified. The other 12 cases were well circumscribed nodules with a variable degree of inflammation and lobular hyperplasia. It is best to recognize these lesions as a heterogeneous group and designate them as lactating nodules, noting any underlying pathological process rather than using the older term lactating adenoma which implies a single neoplastic entity. PMID- 8344659 TI - Mechanism of pain in osteoid osteomas: an immunohistochemical study. AB - Osteoid osteoma is a benign bone tumour characterized by pain which is relieved by non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. To clarify the mechanism of the pain, five osteoid osteomas were studied immunohistochemically using polyclonal antibodies against prostaglandin E2 (PGE2), S-100 protein and protein gene product 9.5 (PGP 9.5). In all five cases, the pain had been relieved by NSAIDs. Nerve fibres positive for S-100 protein and PGP 9.5 were observed in the fibrous zone, especially close to the blood vessels, around the nidus in all the lesions and also within the nidus in three lesions. PGE2 immunoreactivity was variably positive in the nidus of three lesions. In one case a large number of actively proliferating osteoblasts reacted with this antibody. The other cases showed unevenly distributed PGE2 positivity which tended to be prominent in the plump osteoblasts. As control material we examined fibrous dysplasia (3 cases), osteosarcomas (3) and giant-cell tumours of bone (3). The plump osteoblastic tumour cells of three osteosarcomas and the bone forming cells in two cases of fibrous dysplasia gave a positive reaction for PGE2. No S-100 or PGP 9.5 immunoreactive nerve fibres were seen in these lesions. It is concluded that the presence of nerve fibres alone might play a more important role in mediation of pain in osteoid osteomas than some effects of osteoblast-produced PGE2 on the nerves and proliferated blood vessels. PMID- 8344661 TI - The significance of prostatic urothelial dysplasia. PMID- 8344660 TI - Carcinosarcoma of the oesophagus with rhabdomyoblastic differentiation. AB - We report a case of oesophageal carcinosarcoma with prominent rhabdomyoblastic differentiation. Immunohistochemically, the rhabdomyblasts were mainly reactive to vimentin, cytokeratin, desmin, muscle-specific actin, myosin, and myoglobin, and were surrounded by laminin and type IV collagen-positive basement membranes. The tumour had dual differentiation, carcinomatous and sarcomatous, but also showed evident features of transition between the two components; suggesting a common origin. An epithelial-mesenchymal conversion could be the pathogenetic mechanism involved in the histogenesis of this lesion. The word carcinosarcoma, from a descriptive point of view, seems the most suitable to describe a tumour composed of both carcinomatous and true sarcomatous elements. PMID- 8344662 TI - In situ expression of cytokines and serine esterase B in small-bowel allograft rejection. PMID- 8344663 TI - Serous papillary adenocarcinoma of the uterine cervix. PMID- 8344664 TI - Malignant lymphoma and autoimmune disease. PMID- 8344666 TI - New contribution to the genetics of the Basques: heterogeneity in the esterase D subtype distribution. AB - A random sample of 1,491 individuals from three Basque provinces was studied for the red-cell esterase D (ESD) polymorphism by means of isoelectric focusing. The following allele frequencies were observed: Vizcaya, ESD*1 = 0.933, ESD*2 = 0.058, ESD*5 = 0.009; Guipuzcoa, ESD*1 = 0.938, ESD*2 = 0.053, ESD*5 = 0.009; and Alava, ESD*1 = 0.894, ESD*2 = 0.088, ESD*5 = 0.018. The Basques from Vizcaya and Guipuzcoa display the lowest values for allele ESD*5 of any European population studied to date. The value obtained for this allele in the Basque population of Alava is significantly higher than those found in the other two Basque samples. This, together with the fact that Basques from Alava display the lowest ESD*1 frequency of any Basque series, suggests that there are genetic differences between Basque provinces. PMID- 8344665 TI - Survey of the association of deoxyribonuclease I polymorphism with disease. AB - The deoxyribonuclease I (DNase I) system was studied in 120 unrelated Japanese patients with liver disease, malignant neoplasms, alimentary-canal disease and inflammatory conditions with respect to the distribution of phenotypes and gene frequencies in serum samples. In patients with alimentary-canal disease a significant deficit of the DNase I phenotype 1-2 was demonstrated, which suggests that heterozygosity may confer protection against such disease. Furthermore, a significant association between the DNase I phenotype 2 and liver disease was found. The possible involvement of these phenotypes in the response to these diseases would appear to merit further study. PMID- 8344668 TI - Serum protein markers in the Piaroa Indians of Amazonia (Venezuela). AB - A sample of 121 Piaroa Indians from the Federal Amazonia Territory (Venezuela) was studied for the following serum protein polymorphisms: haptoglobin (HP), group-specific component subtypes (GC), orosomucoid (ORM), third component of complement (C3), transferrin C subtypes (TF) and alpha 1-antitrypsin subtypes (PI). The gene frequencies in the whole sample were: HP1 = 0.821; GC1S = 0.698; GC1F = 0.058; GC2 = 0.244; ORMS = 0.434; C3S = 0.699; C3F = 0.289; C3var = 0.012; TFC1 = 0.955; PIM1 = 0.467; PIM2 = 0.004; PIM3 = 0.529. The studied Piaroa sample came from three different communities: Gavilan, Paria and Alto Carinagua. The distribution of GC, C3 and HP polymorphisms was heterogeneous within the three groups. All the examined serum protein markers were polymorphic, in contrast to some enzymatic markers (ADA, DIA, 6PGD, AK) previously studied, which were shown to be monomorphic in the Piaroa. The results were compared with data from other populations living in the same territory. PMID- 8344667 TI - Mendelian phenotypes in The Netherlands. AB - We report here a database listing Mendelian phenotypes described in the Netherlands and/or in populations originating from this country, and describe the results of a quantitative analysis of the database. The database is specifically directed at the presence, frequency and origin of the phenotypes. These are arranged according to their mode of inheritance: autosomal dominant (AD), autosomal recessive (AR) and X-linked. Only those phenotypes which have been reported in accessible sources were included. We entered 1,482 references up to January 1, 1991. At least 672 different loci were described in the Netherlands at this date: 321 (47.8%) AD, 283 (42.1%) AR and 68 (10.1%) X-linked. Almost 2.5% of all loci in our database have no comparable entry in McKusick [mendelian Inheritance in Man, ed 9. Baltimore, The Johns Hopkins University Press, 1990] (MIM). There is a significant difference (p < 0.01) according to the division into AD, AR, and X-linked phenotypes between our database and MIM, in which 61.7% of the phenotypes are AD, 31.5% AR and 6.8% X-linked. Dutch prevalence data for 38 monogenic disorders and 24 polymorphic systems are listed. PMID- 8344669 TI - Distribution of some point mutations in the phenylalanine hydroxylase gene of phenylketonuria patients from the Moscow region. AB - Thirty-one unrelated phenylketonuria patients from the Moscow region were screened for mutations in the phenylalanine hydroxylase gene at the following codons: 408, 158, 261 and IVS-12. For detection of point mutations, polymerase chain reaction amplification was applied with allele-specific oligonucleotide hybridization. The following mutation frequencies were determined: codon 408 56.4%; codon 158-8.1%; codon 261-3.2%, and IVS-12-16%. PMID- 8344670 TI - Linkage studies of cholestasis familiaris groenlandica/Byler-like disease with polymorphic protein and blood group markers. AB - In Greenland, and especially East Greenland (Tasiilaq), a common recessive disease, cholestasis familiaris groenlandica (CFG)/Byler-like disease, occurs in Eskimo children [1]. In a period from 1964-1991, at least 22 children out of about 2,121 newborns were born with this disease (gene frequency q = 0.102). Samples from 126 persons, from a large pedigree in East Greenland including 7 affected and from two families in West Greenland with a total of 3 affected children, have been collected for studying 45 polymorphic markers and for mapping the CFG disease. Polymorphisms and exclusion data were found for the following markers: A1BG, ABO, ACP1, AHSG, C1R, C6, FY, GC, GLO1, GPT, HP, ITIH1, JK, GYPA, GYPB, ORM, P1, PGM1, PI, PON, RH and TCN2. Small positive lod scores (Z < 1.5) were found to the following markers: ITIH1, JK and TCN2. The following markers were nonpolymorphic in this material: ADA, AK1, ALAD, APOA4, APOH, BF, C3, BCHE, CHE2, CO, ESD, FUCA2, F13A1, F13B, KEL, LE, FUT1, LU, PEPD, PGD, PGP, PLG, FUT2, SOD1 and TF. PMID- 8344672 TI - Reassignment of human renin gene to chromosome 1q32 in studies of a (1;4)(q42;p16) translocation. AB - The human renin gene (REN) has been assigned to chromosome 1q42. Linkage studies are, however, inconsistent with this localization. We therefore reexamined the question of the location of REN using a patient whose distal chromosome 1q arm was translocated to chromosome 4 [(1;4)(q42;p16)]. In situ hybridization using a 3H-labelled REN probe demonstrated hybridization signals confined to the q32 band of chromosome 1, with radioactivity in the translocated 1q42 region being similar to the low levels along all other chromosomes. PMID- 8344671 TI - An alternative modality for the immunodetection of the molecular phenotypes of coagulation factor XIIIB. AB - A new technical modality for the typing of coagulation factor XIIIB (F13B) is described. The determination of F13B phenotypes was carried out from desyalized plasma samples by means of polyacrylamide gel isoelectric focusing (pH range 6-8) followed by immunofixation-silver stain. This method combines high sensitivity, low expenditure, and a single methodology. A genetic analysis on F13B phenotypes in the Galician population is also discussed. PMID- 8344673 TI - [Adhesion molecules and homing in inflamed synovia]. AB - The role of adhesion molecules for lymphocyte-endothelial interactions in the synovia of rheumatoid arthritis patients was studied using the frozen section assay. Partial inhibition of lymphocyte binding to endothelium of synovial sections could be observed with antibodies against CD44, L-selectin, beta 1 and beta 2 integrins, pointing to the participation of several adhesion molecules in the regulation of lymphocyte immigration into inflamed synovia. PMID- 8344674 TI - [Syndrome of T gamma lymphoproliferation of Fc gamma RIII- positive lymphocytes in rheumatoid arthritis]. AB - A T gamma-lymphoproliferative syndrome is described in a 69-year-old woman with seropositive rheumatoid arthritis. The phenotype of this non-clonally increased large granular lymphocyte (LGL) population is unusual: LGL are CD56- Fc gamma RIII+(CD16+) and 30% coexpress gamma/delta-T-cell receptor. PMID- 8344675 TI - [Impaired function of polymorphonuclear neutrophilic granulocytes in rheumatoid arthritis]. AB - The aim of this study was to investigate the PMN functions ingestion (I), bacterial killing (BK) as well as the chemiluminescence response to phorbol esters (PMACL) as a measure of PMN respiratory burst activity in RA compared to osteoarthritis and controls. Our findings demonstrated a significant reduction of I and BK in RA compared to OA and controls (p < 0.01 resp.) but an enhanced PMACL (p < 0.01). There was no significant difference of I, BK and PMACL in OA and control subjects. These data clearly demonstrated impaired PMN ingestion and bacterial killing yet enhanced PMACL in RA, thus contributing at least in part to altered host defense in these patients. PMID- 8344676 TI - [IgE rheumatoid factors: occurrence and diagnostic significance]. AB - Sera from 80 patients suffering from rheumatoid arthritis--30 of them with extraarticular manifestations (EAM)--were analyzed for the presence of IgE rheumatoid factors (IgE RF), IgM RF, and immune complexes. Despite of a close correlation between IgM RF and IgE RF, IgE RF allow a better discrimination between patients with and without EAM (73.3 and 38.0%) compared to IgM RF (86.7 and 78.0%). IgE RF could be found in 5% of patients suffering from bronchial asthma, but up to now not in nonrheumatic joint diseases. PMID- 8344677 TI - [Anti-neutrophil-cytoplasmic antibodies in rheumatoid arthritis: specificity and clinical relevance?]. AB - Sera of 90 patients fulfilling the criteria of the American Rheumatism Association for the rheumatoid arthritis (RA) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. All sera were also tested for rheumatoid factor (Waaler-Rose-Test, WRT), C reactive protein (CRP), antinuclear autoantibodies (ANA) on HEp-2 cells. 40% of the 90 sera showed ANCA-positive reactions. c-ANCA and p-ANCA types were both observed but the latter was by far more common (91%). The peculiarity of the p ANCA pattern was a fine granular perinuclear staining. Antibodies against myeloperoxidase (MPO) were negative in all RA sera tested. So far we found a significant relationship between positive ANCA staining, functional Steinbrocker grades, and rheumatoid factor. No significant correlation was observed with extraarticular manifestation, CRP, therapeutic modalities (gold) or MHC antigens. Currently the nature of the neutrophil antigen involved is under investigation. PMID- 8344678 TI - [The matrix metalloproteinase gene family: structure, function, expression, and role in destructive joint disease]. AB - The matrix metalloproteinases, i.e. collagenases, gelatinases and stromelysins, are members of a gene family. They are capable of degrading every component of the extracellular matrix. Tissue destruction observed in inflammatory joint disease is largely accounted for by the action of these enzymes. Among the most potent inducers of metalloproteinase expression are the inflammatory cytokines IL 1 and TNF-alpha. Studies of mechanisms of induction by these mediators at the transcriptional level have improved our understanding of the biological controls of metalloproteinase synthesis. Cytokine inhibitors might serve to inhibit or postpone the crippling consequences of metalloproteinase action. PMID- 8344679 TI - [Anti-centriole antibodies and high neuron-specific enolase activity in a patient with Raynaud phenomenon, cerebrovascular lesions, and ischemic finger necrosis--a functional relationship?]. AB - In a 49-year-old patient with acute thrombangitis obliterans, several vascular risk factors and associated features of collagen vascular disease, we observed anti-centriole autoantibodies and a strongly elevated neuron-specific enolase (NSE). The latter could not be attributed to an underlying malignant or neuroendocrine disease. The recent identification of NSE as a centrosomal protein suggests a causal relationship between anti-centriole autoantibodies and elevated serum NSE levels. PMID- 8344680 TI - [Cyclophosphamide bolus therapy in lupus nephritis--status of the clinical study]. AB - In order to establish a low-dose cumulative cyclophosphamide therapy for lupus nephritis, 21 patients were either randomized for at least 3 i.v. cyclophosphamide pulses until remission occurred or for 12 pulses. 18/21 patients developed a remission after an average of 7.3 pulses and a cumulative cyclophosphamide dose of 9.3 g. Side effects were only mild. PMID- 8344681 TI - [Immunoglobulin therapy for systemic lupus erythematosus]. AB - A 25-year-old patient with lupus erythematosus was admitted with myositis and erythema of the skin under chloroquine therapy. After improvement of clinical symptoms with cyclophosphamide and prednisolone he was again progredient with myositis. The changing of therapy to methotrexate showed a hepatotoxic side effect with elevated liver enzymes. Under subsequent therapy with azathioprine and prednisolone he developed leukopenia and sepsis. Because of persistent erythema of the skin under therapy with different immunosuppressives we performed a therapy with high-dose intravenous immunoglobulins. After application of immunoglobulins we observed an improvement of the erythema after 10 days, which was persistent after dose reduction for about 4 months. PMID- 8344682 TI - [Pulmonary thromboembolism in antiphospholipid syndrome]. AB - The case of a young woman is presented who suffered from thromboembolic pulmonary hypertension. Thrombocytopenia developed late in the course of the disease and led to the diagnosis of secondary antiphospholipid syndrome. PMID- 8344683 TI - [Reduced "oxidative burst" in a granulocyte subpopulation in a case of Sweet syndrome]. AB - Oxidative burst was defective in 50% of peripheral blood neutrophils in a case of Sweet syndrome with leukemoid granulocytosis. Phagocytosis was normal. We suggest that the decreased ability to produce oxygen radicals observed in this patient might lead to a compensatory recruitment of hematopoietic growth factors. Consecutive activation, increased chemotaxis and adhesion of polymorphonuclear granulocytes might be the cause of the neutrophilic dermal infiltrate of Sweet syndrome. PMID- 8344684 TI - [The mucosa-associated immune system--immune defense in the gastrointestinal tract]. AB - The intestinal immune system has to protect the mucosa against microbial and toxic agents. This is achieved by elimination of potential antigens, which are inhibited to adhere and to invade the mucosa. Thus, induction of inflammatory processes is prevented. Elimination of antigens is mediated by the secretion and transport of IgA (and especially IgA2) to the lumen of the gut. There, IgA is the most efficient part of the so-called "mucosa block". The composition of mononuclear cells in the lamina propria exhibits the preference of a memory T cell type that is able to provide help for B cells. If IgA-mediated immune response proves not to be sufficient, IgG-mediated inflammatory processes are induced within the mucosa. The role of cytotoxic T cells and, moreover, the biological function of intraepithelial lymphocytes are still controversial. PMID- 8344685 TI - [Follow-up study of the development of autoantibodies in patients with chronic inflammatory bowel disease under anti-CD4 therapy]. AB - 7 of 22 patients with chronic inflammatory bowel diseases (Crohn's disease, ulcerative colitis) were treated with an anti-CD4-mAb. In the immunological monitoring the amounts of autoantibodies to pancreatic acini cells, to intestinal goblet cells, to granulocytes with perinuclear fluorescence pattern were examined and human anti-mouse-antibodies were measured. After anti-CD4 therapy the production of autoantibodies was widely unchanged. Therefore its use as parameter in the follow-up is restricted. PMID- 8344686 TI - [Therapy of Crohn disease by immunomodulation with 7S immunoglobulins]. AB - Immunoregulatory disturbances play an important role in pathophysiology of Crohn's disease. Because of this fact we tried to improve the situation in therapy-resistant cases by additional intravenous application of 10 g 7S immunoglobulin (Venimmun) for 10 days. The first patient with active Crohn's disease (CDAI 209) showed a steroid-related psychosis. Therapy had to be changed. During therapy with immunoglobulin Crohn's disease activity index decreased by 97 points. Activity index fell in another patient during therapy from 363 to 150 points. Both patients came into remission by additional therapy with 7S immunoglobulin. The number of leucocytes decreased and the number of lymphocytes increased. CD4/CD8 ratio in the peripheral blood changed in favour of suppressor cells and soluble interleukin-2 receptors were reduced. Immunoregulatory effects seem to be responsible for successful immunoglobulin therapy in Crohn's disease. PMID- 8344687 TI - [Characterization of allergens of timothy grass (Phleum pratense)]. AB - By means of 2-D electrophoresis and subsequent immunoblotting allergens of timothy grass pollen are separated as single components. Via N-terminal sequencing, it is possible to classify these components as isoallergens of defined groups according to the allergen nomenclature. We are able to identify the allergens as Phl p I, Phl p IV, Phl p V and Phl p VI. PMID- 8344688 TI - [Circadian rhythm in cytokines]. AB - The well-known human circadian rhythm (CR) in body temperature may be due to CR in endogenous pyrogens such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF). We, therefore, investigated the daily variation in spontaneous and LPS-induced monokine release by peripheral blood cells (whole blood assay) in 10 healthy volunteers. Spontaneous release of monokines (IL-1, IL-6, TNF) showed a simultaneous significant peak at noon, whereas LPS-induced release of IL-1 and IL-6 was strictly correlated with the CR in body temperature with its significant maximum at 8.00 p.m. Since LPS-induced release of TNF showed a significant peak at 4.00 a.m., interleukins and TNF seem to be independently regulated. CR in IL-1 and IL-6 release are suggested to be responsible for the CR in body temperature. PMID- 8344689 TI - [20th conference of the clinical immunology group--a retrospective]. PMID- 8344690 TI - [Preliminary results in a placebo-controlled, double-blind crossover clinical trial with human interleukin-2 (n-IL-2) in patients with variable immunodeficiency syndrome (CVID)]. AB - Ten CVID patients with an in vitro defect for IL-2-synthesis were treated for 12 months in a placebo-controlled double-blind crossover therapy study with human natural IL-2 s.c. There were no severe side effects of n-IL-2 recorded. Serum levels of soluble IL-2 receptors were unaffected by the therapy. Serum IL-2 levels were only measurable in single patients during the therapy phase. Since verum and placebo groups did not differ with respect to requirement for intravenous gammaglobulin substitutions, n-IL-2 therapy was uneffective in switching on IgG synthesis in vivo. Nevertheless, there was an elevation in vitro of IgM synthesis in 5 patients and of IgG synthesis in 4 patients during n-IL-2 therapy after stimulation of patients' lymphocytes with staphylococcus aureus Cowan I (SAC) plus n-IL-2 or with Pokeweed Mitogen (PWM) without n-IL-2. Additionally, an elevated IL-2-synthesis in vitro was recorded after OKT3 stimulation for 3 CVID patients. There was a significant reduction of severe infections from 25 during the first 6 months of the study to 7 infections during the following 6 months, in the group of patients which received n-IL-2 first. In the second group, which received placebo first, there were no significant differences between placebo and n-IL-2 therapy phase detectable (25 infections during the first 6 months of the study and 24 severe infections in the second phase).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344691 TI - [In vitro IL-6- and immunoglobulin-production in patients with variable immunodeficiency syndrome (CVID)]. AB - In vitro immunoglobulin and IL-6 synthesis were investigated in patients with CVID and healthy controls. The IL-6 production was increased in CVID patients. However, after calibration to equal monocyte counts in the mononuclear cell population the difference between patients and controls was no longer significant. The immunoglobulin production in CVID was decreased but no correlation between immunoglobulin and IL-6 production was found. From these results we suggest that monocyte activation might be of importance in terms of secondary organ lesions frequently occurring in CVID patients. PMID- 8344692 TI - [Wegener's granulomatosis and ANCA-associated vasculitis: pathogenic role of autoantigens, autoantibodies, and cytokines]. AB - A real explosion of data is seen concerning the detection of autoantibodies collectively known as antineutrophil cytoplasmic antibodies (ANCA) recognizing granule proteins of granulocytes and monocytes. Distinct fluorescence staining patterns result from their diverse substrate specificities, and can even identify several disease entities mainly in the etiopathogenetically unclear group of primary systemic vasculitides (PSV). The well-documented disease specificity of ANCA recognizing proteinase 3 (PR3), and recent in vitro findings concerning the effect of cytokines on immunocompetent cells including the endothelium are the rationale for the presentation of a new model explaining the development of systemic vasculitis. PMID- 8344694 TI - [Silicosis and systemic diseases]. AB - We present case histories of 5 patients with silicosis who developed systemic lupus erythematosus and microscopic polyarteritis in two cases each, and rapidly progressive glomerulonephritis (limited Wegener's granulomatosis) in one case. An association between silica exposure and autoimmune disease is emphasized. PMID- 8344693 TI - [Post infection antiidiotype vaccination against HIV: results of a phase Ia pilot study]. AB - The mAb IOT4A against the HIV-gp 120 binding site on CD4 was shown to elicit the production of specific anti-idiotypes in rabbits neutralising HIV-1 in vitro. This study was designed in order to determine the safety and efficacy of the mAb IOT4A for the immunization of HIV+ volunteers. 10 patients in stages WR2-WR4B of HIV-disease were given six s.c. injections of the mAb IOT4A as an alum precipitate (each 3 patients receiving 0.6 or 1.2 mg, 4 patients receiving 2.4 mg). 6 patients subsequently received a booster immunization with the same dose of the mAb IOT4A. The immunization schedule was accompanied by monitoring clinical, immunologic and virologic parameters. No systemic toxic or allergic effects of the idiotype vaccine were observed. 8/10 vaccinees displayed a delayed type hypersensitivity at the location of antibody administration beyond the third injection. The relative and absolute CD4 count showed a sustained increase in 8/10 patients at the end of the booster immunization and an additional raise after booster immunization in 6/6 patients. 624 antigen levels became negative in 2/2 patients during vaccination. In 4/10 patients in increase in HIV/gp 120 antigen binding titres was observed. HIV neutralisation titer remained stable throughout the observation period, and no progression in HIV disease was observed in all patients included in this study. The administration of the mAb IOT4A as a vaccine in HIV-infected volunteers was well tolerated. The mAb ITO4A induced the production of specific anti-idiotypes, that might have been of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8344695 TI - [Interferon alpha antibodies show no cross reactions with typical autoantibodies]. AB - Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens. PMID- 8344696 TI - [Autoimmune diseases]. AB - The etiology and pathogenesis of so-called autoimmune diseases are only known in rare examples. This speculative review argues that autoimmune diseases, particularly those mediated by, or dependent upon T cells may represent immunopathologies triggered by unrecognized infectious agents. Accordingly, when the etiologic agent is recognized, we call the ensuing disease immunopathological, where it is not known the disease is called autoimmune. PMID- 8344697 TI - [Virus and autoimmunity with emphasis on liver diseases]. AB - The dualism virus pathogenesis and autoimmune pathogenesis in liver disease is given up increasingly. A survey is given about the development of autoimmunity and virus induction of the autoimmune hepatitis. The hypothesis of virus induction of autoimmune hepatitis put forward by Storch 1975 (19) is unproven up to now, but the concept of virus-associated autoimmune hepatitis put forward by Storch 1980 (23) is acknowledged today. First of all, antibodies against endoplasmic reticulum (liver and kidney microsomes) type 1, liver ribosomes, and liver cell cytoplasm are regarded as markers of a hepatitis C virus-associated autoimmune hepatitis. At present it is unknown, if antibodies against the surface of tongue epithelium, basal cells of squamous epithelium, Golgi apparatus, and nerve cells are further suitable markers. PMID- 8344698 TI - Schistosoma japonicum soluble egg antigens activate naive B cells to produce antibodies: definition of parasite mechanisms of immune deviation. AB - This study analysed the effect of Schistosoma japonicum egg antigens (SEA) on the activation of lymphocytes from naive mice. T cells were found to be unaffected by SEA. B cells, however, were activated by SEA without participation of adherent cells such as macrophages. B-cell activating factor(s) in SEA were distributed into a fraction of M(r) 120,000 and a fraction of M(r) 650,000 by gel filtration. However, a fraction of M(r) 120,000 demonstrated the presence of a limited number of components by polyacrylamide gel electrophoresis (PAGE) under non-denaturing conditions. These activating factor(s) were destroyed by peroxidase oxidation, heat treatment, chymotrypsin and trypsin digestion. These results indicate that the B-cell activating factor(s) in SEA contain both carbohydrate and protein. IgM antibodies were detected in the culture supernatant of SEA-activated B cells after 48 hr in culture, but IgG antibodies were undetected in culture. These antibodies did not react with SEA but reacted with sheep, horse, mouse red blood cells, carbonic anhydrase and autoantigens in myelinated nerve fibres of cerebrum as well as luminal surface and parietal cells of the stomach of naive mice. Thus our data demonstrated that SEA directly stimulates naive B cells to produce antibodies against heterophile and autologous antigens. PMID- 8344699 TI - The interaction of Tamm-Horsfall protein with the extracellular matrix. AB - Tamm-Horsfall protein (THP) is the major glycoprotein component of urine, yet its biological role remains obscure. Recent reports have suggested that a concanavalin A (Con A)-binding fraction of THP from pregnancy urine can bind the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). In order to investigate this claim in relation to THP from normal adult urine we raised monoclonal antibodies to THP and sought THP/TNF-alpha interactions in three separate assay systems. We found no evidence that THP binds to TNF-alpha under physiological conditions, but we observed that it exerts a weak, probably not physiologically relevant, but reproducible inhibitory effect on the toxicity of TNF-alpha for monolayers of L929 cells, even when the cells are pretreated with the THP, and washed before addition of the cytokine. Since our preparations of THP do not interact directly with TNF-alpha we postulated an interaction with the cells themselves, or with their extracellular matrix. The THP was found by ELISA, immunoblotting and immunohistology, to bind to as yet unidentified components of the extracellular matrix in a manner dependent on cations, pH and carbohydrates. These data, considered in the light of the published amino acid sequence and biochemical properties, suggest that THP is a member of a structural glycoprotein family known to modulate cell adhesion. PMID- 8344700 TI - Down-regulation of cytokine production and interleukin-2 receptor expression by pooled human IgG. AB - The influence of pooled human IgG preparations for intravenous use (i.v.Ig) on in vitro-induced cytokine production was studied at the single-cell level using cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescent technique. Cultured mononuclear cells from peripheral blood from healthy adult donors were polyclonally stimulated for 96 hr by either direct ligation of T-cell receptors using immobilized anti-CD3 mAb or by a combination of a protein kinase C activator [phorbol 12-myristate 13-acetate (PMA)] and a calcium ionophore (ionomycin) in the absence or presence of i.v.Ig. A marked inhibition of proliferation and blast transformation was noted in all i.v.Ig exposed cultures, despite good cell survival. The production of the T-cell lymphokines interleukin 2 (IL-2), IL-10,interferon-gamma (IFN-gamma) and tumour necrosis factor-beta (TNF beta) was significantly down-regulated during the whole studied period in the i.v.Ig containing anti-CD3 stimulated cultures. The synthesis of the monokine IL 8 was not suppressed and that of TNF-alpha, which was made by both lymphocytes and monocytes, was only moderately inhibited. Somewhat different and more transient effects were observed in the i.v.Ig-exposed PMA/ionomycin-activated cultures. The production of IL-2, IL-3, IL-4, IL-5, IL-10, TNF-beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) was down-regulated during the initial phase of the cultures up to 48 hr, but not at 48-96 hr. The synthesis of IFN-gamma and TNF-alpha was unaffected of the influence of i.v.Ig during the entire culture period. The expression of IL-2 receptors (IL-2R) was significantly suppressed in the i.v.Ig-treated anti-CD3-activated cells, but not in the PMA/ionomycin-stimulated cultures. Taken together our results indicate that pooled IgG may mediate immunomodulation by direct effects on cytokine production and on T-cell proliferation. PMID- 8344701 TI - Characterization of unique lymphoid cells derived from murine spleen which constitutively produce interleukin-6. AB - Attempts have been made to isolate continuous lines of rare subsets of lymphoid cells present in murine spleen in order to analyse their function and lineage relationship with respect to other lymphoid cells. Mitogenic stimulation was used to expand the lymphoid cells remaining in spleen following depletion of CD4+ and CD8+ T cells by antibody and complement treatment. Cells were cultured in the presence of concanavalin A (Con A), interleukin-2 (IL-2) and syngeneic irradiated spleen feeder cells. This procedure expanded a population of non-T-, non-B lymphoid cells bearing a common, unique phenotype resembling lymphoid precursors. Eight cloned lines from B10.A(2R) and B10.A(5R) strains of mice have been analysed here. Analysis of cell surface marker expression has revealed positive expression of class I and class II major histocompatibility complex (MHC) antigens, CD44, CD45 (T200 and B220) but expressing no markers unique to T, B or myeloid cells. All cell lines represent agranular lymphoblasts and show no evidence of early T-cell receptor (TcR) or Ig heavy chain gene rearrangements, suggesting no commitment to T-or B-lymphoid lineage. Despite expression of the NK1.1 marker for natural killer (NK) cells, none of the cell lines has been shown to have cytotoxic function for NK targets, nor could cytotoxic function be induced following various activation procedures. Analysis of lymphokine production has revealed no detectable IL-1, IL-2, IL-3, IL-4, IL-5, tumour necrosis factor-alpha (TNF-alpha) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in cell supernatants. However, all but one of these cell lines constitutively produce IL-6. Each cell line has been shown to induce T-cell proliferation independently in mixed lymphocyte reactions, implicating the capacity of these cells to act as antigen-presenting cells. Consistent with this hypothesis is the observation that these cells also demonstrate endocytic activity for foreign proteins. This was visualized by their uptake of fluoresceinated albumin into cytoplasmic granules. Since they express many cell surface markers common to described isolates of spleen dendritic cells, including both class I and class II major histocompatibility molecules, they would appear to represent the first example of continuous lines of this rare cell subset. PMID- 8344702 TI - Effect of retinoic acid and vitamin D on the expression of interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 in the human monocytic cell line U937. AB - We have previously described a synergism between the two physiological hormones, retinoic acid (RA) and 1 alpha,25-dihydroxyvitamin D3 (VD) in the induction of U937 cell differentiation towards a more mature state. Herein, we investigated the regulation of cytokine production during RA and/or VD treatment of U937 cells. Cell differentiation was followed by measurement of their capacity to give oxidative responses, and interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and IL-6 gene and protein expression were determined in RA/VD treated cells, activated or not with lipopolysaccharide (LPS). The undifferentiated and RA-treated U937 cells were unable to produce monokines even when they were stimulated by LPS. VD induced the monokine mRNA expression in U937 cells but failed to induce protein release. However, unlike RA, it primed the cells to secrete monokines upon endotoxin stimulation. A large enhancement of the production of the monokines both at mRNA and protein levels was observed in the U937 cells exposed to the combination of RA + VD. Nevertheless, protein release required a further step of activation of the RA + VD-primed cells. The co-inducer effect of RA and VD was not observed in HL-60 or THP-1 cells and seems to be restricted to U937 cells. These results on cytokine expression support our previous finding that a combination of RA and VD brings the U937 cells to a high stage of myeloid differentiation with major characteristics of monocytes/macrophages. PMID- 8344703 TI - C3 synthesis by A549 alveolar epithelial cells is increased by interferon-gamma and dexamethasone. AB - The third component of complement, C3, is produced in the lung by several cell types including alveolar epithelial cells. Since interferon-gamma (IFN-gamma) and dexamethasone regulate C3 gene expression in non-pulmonary cells, and because IFN gamma and dexamethasone interact to regulate the functional activity of alveolar epithelial cells, we investigated the effects of IFN-gamma and dexamethasone on C3 production by A549 human alveolar epithelial cells. Treatment of A549 cells with IFN-gamma alone increased C3 production in a time-and dose-dependent manner. Maximal increase in C3 production occurred after stimulation of A549 cells with 500 IU/ml IFN-gamma for 3 days and was 3.4-fold greater than control. Dexamethasone (0.1 microM) stimulation of A549 cells increased C3 production 6.7 fold over controls on day 3. Treatment of A549 cells with IFN-gamma plus dexamethasone resulted in an 11-to 13-fold increase in C3 synthesis. C3 mRNA levels were increased in A549 cells treated with IFN-gamma and dexamethasone individually and in combination suggesting that IFN-gamma and dexamethasone increase C3 synthesis by a pre-translational mechanism. IFN-gamma and dexamethasone did not alter the two-chain structure of the C3 molecule produced by A549 cells, as assessed by Western blotting. We speculate that IFN-gamma and glucocorticoids may be important in the local regulation of C3 synthesis in the lung. PMID- 8344705 TI - UVB irradiation renders corneal allografts tolerogenic for allospecific delayed hypersensitivity responses. AB - Heterotopic corneal allografts treated with ultraviolet (UV) radiation not only failed to elicit allospecific delayed-type hypersensitivity (DTH) responses in mice but rendered the hosts tolerant to subsequent immunization with normally immunogenic corneal allografts. The immunological tolerance induced by UV-treated grafts was cyclophosphamide sensitive and antigen specific. Adoptive transfer studies revealed that the tolerance to donor alloantigens could be transferred with CD4+, CD8- T cells which suppressed alloimmune DTH responses at the afferent but not the efferent limb. The capacity of UV-treated corneal allografts to induce allospecific tolerance was related to UV irradiation and not simply a result of loss of corneal viability. Formalin-fixed corneal allografts could not produce similar tolerization for DTH responses. Selective debridement of either the corneal epithelium or endothelium revealed that the corneal endothelium was the critical layer necessary for UV-dependent tolerance induction. Furthermore, the initial exposure to UV irradiation must occur through the endothelium and not the epithelium. Thus, the single-cell layered corneal endothelium is the target for the immunomodulatory effects of UV irradiation on corneal allografts. PMID- 8344704 TI - T-cell activation. VI. Inhibitory and stimulatory effects of anti-major histocompatibility complex class I antibodies in allogeneic mixed lymphocyte culture. AB - Murine T splenocytes stimulated in primary allogeneic mixed lymphocyte culture (MLC) were incubated with soluble anti-major histocompatibility complex (MHC) class I monoclonal antibodies. These antibodies induced inhibition in the cytotoxicity of the responding population and this inhibition was not dependent on the domain on class I molecules recognized by the antibodies. Cross-reactivity of the antibodies between the responder and stimulating cell population caused a marked reduction in the inhibitory effect compared to systems where no such cross reactivity was present. Saturating levels of the antibodies caused a reduction in generation of T-cell cytotoxicity, whereas low concentrations stimulated the same response. These results demonstrate that the MHC class I molecules of T cells are of significant importance in antigen-induced signal transduction. PMID- 8344706 TI - Variations in serum sCD23 in conditions with either enhanced humoral or cell mediated immunity. AB - Soluble CD23 (sCD23) is increased by interleukin-4 (IL-4) and decreased by interferon-gamma (IFN-gamma). On the basis of cytokine profiles T-helper (Th) cells may be functionally divided into IL-2- and IFN-gamma-secreting Th1 cells, which are involved in cell-mediated immunity (CMI), and IL-4- and IL-5-producing Th2 cells, which are involved in humoral immunity. Compared with sex-matched controls (median 8.5) we found significantly elevated levels of serum sCD23 in patients with rheumatoid arthritis (median 22.7, P < 0.0002), with the highest levels detected in patients fulfilling an increasing number of the American Association revised criteria for rheumatoid arthritis. Soluble CD23 levels were also significantly raised in autoimmune thyroiditis (median 11.7, P < 0.02) and myasthenia gravis (median 10.4, P < 0.05). In contrast patients with either coeliac (median 6.5) or Crohn's disease (median 5.8) had reduced levels of sCD23 compared to appropriate controls (median 11.8), in both cases significant at P < 0.01. Variations in sCD23 may, therefore, reflect enhanced Th1 activity in the two later conditions in contrast to heightened Th2 activity within the three classical autoimmune conditions. PMID- 8344707 TI - Renal allograft rejection: protection of renal epithelium from natural killer cells by cytokine-induced up-regulation of class I major histocompatibility antigens. AB - The potential of natural killer (NK) cells to contribute to renal allograft rejection was modelled by mixing NK cells with cultured renal epithelial cells. It was found that the renal cells were readily lysed by cytokine-activated NK cells. Renal cells which were previously stimulated by culture with either interferon-gamma (IFN-gamma) or supernatant from mixed leucocyte cultures (MLC) were relatively resistant to such lysis; stimulation with tumour necrosis factor alpha (TNF-alpha) had no effect. None of these cytokine preparations had any effect on the lysis of renal cells by either specific cytotoxic T lymphocytes or the antibody-dependent cell-mediated cytotoxic mechanism. The expression of class I major histocompatibility complex (MHC) antigens was up-regulated by stimulation of renal cells with either IFN-gamma or MLC supernatant; treatment with TNF-alpha had no effect on the expression of these antigens. Protection from NK cell mediated lysis appeared to correlate with the expression of class I MHC antigens by the renal cells. Artificial removal of these MHC antigens by treatment with citric acid significantly increased the susceptibility of cytokine-stimulated renal cells to lysis by activated NK cells. This increase was not caused by enhanced binding of NK cells to acid-treated renal cell targets. These results suggest that high levels of class I MHC antigen expression block NK cell triggering after engagement with renal epithelial cells. It is concluded that cytokines present within the renal microenvironment during rejection protect graft cells from lysis by NK cells by causing local upregulation of the expression of class I MHC molecules. PMID- 8344708 TI - The mechanisms of IgE uptake by human alveolar macrophages and a human B lymphoblastoid cell line (Wil-2wt). AB - Human alveolar macrophages (HAM) internalized more IgE (81%) than human Wil-2wt B lymphoblastoid cells (28%) suggesting a difference in the metabolic processing of the specific IgE receptor (CD23) or, alternatively, the presence of another functionally distinct receptor. The mannose receptor (MR), demonstrated to be present on the AM, may fulfil this role as IgE is heavily mannosylated and binds to a greater extent to concanavalin A (Con A) (which has specificity for oligomannose oligosaccharide chains) than other antibody isotypes. The hypothesis of a second IgE receptor was tested using mannan which is a competitive inhibitor of ligand binding to the MR and mannosylated bovine serum albumin (MBSA) which binds with avidity to the MR. Mannan (0.1 mg/ml) decreased internalized MBSA uptake in the HAM at 37 degrees suggesting the presence of the specific MR. In contrast, Wil-2wt cells did not bind MBSA. Mannan also reduced IgE uptake in the HAM at 37 degrees but had no effect on IgE uptake by Wil-2wt cells. Anti-CD23 monoclonal antibody (mAb) 135 also partially reduced membrane IgE uptake in HAM while completely inhibiting it by Wil-2wt cells. However, there did not appear to be competition for binding sites between IgE and MBSA in HAM. If only CD23 is involved in IgE uptake by HAM its function appears to be different to that in Wil 2wt cells. Definite involvement of the MR in IgE uptake will require further investigation as it may have an important role in allergic states. PMID- 8344710 TI - Cell-surface expression of human histocompatibility leucocyte antigen (HLA) class II-associated invariant chain (CD74) does not always correlate with cell-surface expression of HLA class II molecules. AB - The human histocompatibility leucocyte antigen (HLA) class II-associated invariant chain comprises at least four polypeptides. One of these is expressed as a membrane-bound subunit and has been designated as CD74. We investigated the expression of CD74 on B- and T-cell types utilizing monoclonal antibodies (mAb) specific for the c-terminus of CD74. All B cells tested expressed CD74 regardless of their HLA phenotypes. High and low CD74 expressors were provisionally assigned based on quantitative variations found in some haplotypes. A mutant cell with selective deletions of class II loci DR and DQ but with retention of DP and additional class II heterodimers synthesize normal amounts of CD74. In contrast, however, a mutant with a total class II deletion had diminished expression of CD74, suggesting that at least one of the class II isotypes is essential for full constitutive expression of CD74. Major histocompatibility complex (MHC) class II negative T-cell lines and CD3+ T cell isolated from peripheral blood did not express CD74. However, allostimulated T cells which express de novo induced class II determinants also did not express CD74. Taken together, these results show that CD74 is expressed on B cells and unexpectedly is not synthesized on de novo induced class II positive T-cell clones. PMID- 8344711 TI - Co-operation of interleukin-1 beta and tumour necrosis factor-alpha in the activation of human umbilical vein endothelial cells to inhibit Toxoplasma gondii replication. AB - The tachyzoites of the RH strain of Toxoplasma gondii invaded and replicated in cultured human umbilical vein endothelial cells (HUVEC). Co-treatment of the HUVEC with human recombinant interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) inhibited the replication of T. gondii. Growth of the parasite was measured in vitro by [3H]uracil incorporation assay 18 hr after infection. This assay showed that when cells were pretreated with IL-1 beta and TNF-alpha concentrations ranging from 1 to 100 U/ml, a high degree of inhibition was observed with a phenomenon of co-operation causing a dose-dependent inhibition of the replication of intracellular T. gondii. The mechanism(s) by which the inhibition of multiplication was effected remains to be elucidated. PMID- 8344709 TI - Eosinophil accumulation induced by human interleukin-8 in the guinea-pig in vivo. AB - Interleukin-8 (IL-8) is a neutrophil chemoattractant cytokine. Initially IL-8 appeared to exhibit specificity for neutrophils over other cells of the immune system. However, several recent studies have shown that this mediator can also activate other leucocyte types in vitro. In this study we have used an in vivo model of local [111In]leucocyte accumulation in the guinea-pig and an in vitro assay of leucocyte activation (changes in cytosolic-free Ca2+) to investigate the eosinophil chemoattractant activity of IL-8. The intradermal injection of recombinant human (rh)IL-8 induced a dose-dependent accumulation of intravenously administered [111In]eosinophils into the skin sites over 4 hr. Time-course experiments revealed that this cell infiltration was delayed in onset, occurring between 1 and 2 hr after injection of IL-8. The delay may indicate that IL-8 operates via an indirect mechanism. In contrast, eosinophil accumulation induced by the complement fragment C5a occurred within the first hour following injection. Other human cytokines, IL-1, IL-3, IL-5, tumour necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), were not eosinophil chemoattractants in this in vivo test system. Direct activation of eosinophils by IL-8 was demonstrated in vitro by a transient elevation in cytoplasmic-free Ca2+ levels where it was less potent than either rhC5a or leukotriene B4 (LTB4). Experiments using [111In]neutrophils in vivo indicated that rhIL-8 and rhC5a were similar in potency in inducing local neutrophil infiltration into guinea-pig skin. The demonstration of the eosinophil chemoattractant activity of IL-8 in vivo raises the possibility that this cytokine, or a structurally related molecule, contributes towards eosinophil infiltration in a number of inflammatory conditions such as asthma, helminthic infections and adult respiratory distress syndrome. PMID- 8344712 TI - Peripheral blood neutrophils from HIV-1-infected individuals are armed with factors that cause inhibition of their migration in response to specific antigens. AB - In this study, synthetic peptides that copy conserved regions of the HIV-1 envelope proteins gp120 and gp41 were tested for their impact on the chemotaxis of leukocytes and neutrophils from HIV-1-infected individuals, while neutrophils from HIV-1-infected patients were tested for their effect on the chemotaxis of neutrophils from healthy donors. The synthetic peptides (corresponding to the 251 272-amino acid sequence of gp120 and the 584-618-amino acid sequence of gp41) were capable of specifically inhibiting the formyl peptide-induced chemotaxis of cells from HIV-1-infected patients, and such inhibition was observed both with a total leukocyte population and with pure neutrophils. The migration of neutrophils from healthy donors was specifically inhibited in the presence of either of the synthetic peptides of HIV-1 envelope proteins after their incubation with neutrophil supernatants obtained from HIV-1-infected individuals. As shown by ELISA tests, the neutrophil supernatants from HIV-1-infected individuals contain antibodies to a recombinant env-1 protein that might be one of the reasons for the specific arming of neutrophils from HIV-1-infected persons. PMID- 8344714 TI - Enhancing effect of 17 beta-estradiol on human NK cell activity. AB - The in vitro effect of 17 beta-estradiol on NK activity was studied. The proliferation and NK activity of YT-N17 (a human NK-like cell line) were enhanced by 17 beta-estradiol (E2), and the enhancement was blocked by tamoxifen (Tx), an antagonist of E2. On the contrary, other steroid hormones such as Tx, progesterone, and testosterone had no effect. YT-N17 contained 11.8 fmol/mg protein of estrogen receptor (mean of two independent assays), a value which was 5-10-fold higher than that of other hematopoietic cell lines. An enhancement of NK activity by E2 was also seen in large granular lymphocytes obtained from normal subjects, and it was again suppressed by Tx. These data suggest that E2 is one of the activating factors for NK/LGL cells. PMID- 8344713 TI - Analysis of the hairless mouse as a model for the effects of aging on the immune system. AB - Studies into the effects of aging on the immune system are hampered by the lack of a suitable animal model that is readily available and cost efficient. The mutant mouse, hairless (hr/hr genotype), has been shown to undergo an accelerated thymic involution with accompanying immunodeficiency. Thus, this strain of mouse has been proposed as a model for studying the interactions of aging and immune function. We have investigated the effects of homozygous hr gene expression over time on the immune function of these mice. It was observed that homozygous hr gene expression had minimal effects on peripheral lymphocyte subset compositions but did appear to result in changes in thymic differentiation. Further, hr/hr mice displayed decreased proliferative responses to IL2 and mitogen stimulation, although cytotoxic responses (both NK and T cell mediated) appeared normal. These defects appear to be attributable to T helper cell dysfunction. Each of the changes found in hr/hr mice were distinct from those seen with age-matched control mice. Thus, the hr/hr inbred strain of mouse does not appear to be a suitable model for use in analyzing the effects of aging on the immune system. PMID- 8344715 TI - The effect of IL-4 on the phenotype of a human B-cell lymphoma line (Farage) lacking immunoglobulin expression. AB - Farage cells do not express surface immunoglobulins (sIg) but display a high level of CD19, CD21, CD22, CD23, CD39, CD40 B-cell antigens, and various adhesion proteins, such as CD11a (LFA-1), CD29 (VLA-4), CD44, CD54 (ICAM-1), and CD58 (LFA 3). The phenotype of Farage resembled that of EBV-LCL but differed from the phenotype of Burkitt's lymphoma lines, which were CD39- CD44-, expressed a high level of CD38, and either lacked CD21 or were weakly positive. Exposure to IL-4 augmented the concentrations of CD23 and of adhesion proteins on the surface of Farage cells but diminished the expression of CD21, CD22, and CD38. IL-4 did not induce the expression of sIg on Farage cells and failed to affect the level of HLA-DR. IL-2 and TPA did not alter the level of CD21 and adhesion proteins on Farage cells. Although IL-4 induced unique changes of the antigenic pattern in Farage, no significant effect on the phenotype of Burkitt's lymphoma lines was detected after IL-4 treatment. The present study indicates that the responsiveness of B cells to IL-4 is not determined by the expression of sIg but rather is associated with the antigenic profile characteristic for non-germinal center B lymphocytes. PMID- 8344716 TI - Enhancement of systemic and mucosal immune responses following oral administration of liposomes. AB - The effects of liposomes on the systemic and mucosal immune response were investigated using bovine serum albumin (BSA) in BALB/c mice. Following three oral administrations of varied formulations at 1-week intervals, serum BSA specific IgG levels were increased significantly by BSA encapsulated in liposomes and moderately by a mixture of liposomes and BSA. Serum and salivary BSA-specific IgA levels were elevated by BSA-encapsulating liposomes only. Liposomes thus activate not only the systemic immune response but also the mucosal immune response following their oral administration. However, no increase in salivary IgA levels was observed by intraperitoneal or subcutaneous injection of BSA encapsulating liposomes. The production of IgA is closely related to the oral administration of liposomes encapsulating antigens. Liposomes thus function as carriers of oral vaccines against various infections of the mucosal surface. PMID- 8344717 TI - Isolation and amino acid sequence of a chemotactic protein, LECT/interleukin 8, from a human myeloid leukemia cell line, ML-1. AB - We looked for chemotaxin/interleukin 8 (CT/IL-8) activity in the culture fluids of 97 human leukemia cell lines and found it in two of the T cell lines, six of the myeloid cell lines, and one of the normal B-cell lines. It was particularly strong in the culture fluids of two cell lines. These cell lines secreted a chemotactic protein into the culture fluids under certain conditions of stimulation with phorbol-12-myristate 13-acetate (PMA), lipopolysaccharide, or hemagglutinin-P. A myeloid leukemia cell line, ML-1, secreted an inducible chemotaxin when stimulated with PMA (1 ng/ml) for 24 h. We purified the chemotaxin from ML-1 cell culture fluid using an improved procedure: concentration with DEAE-Sepharose CL-6B and CM-Sepharose CL-6B, CM-Sepharose column chromatography, and reverse-phase 5TMS-300 column on HPLC with the retention time coinciding with that of LUCT/IL-8 [Suzuki et al., 1989, J. Exp. Med. 169, 1895]. The yield was 200 micrograms protein from 6 liters of the culture fluid. The N terminus of CT/IL-8 was AVLPR-SAKELRXQXIKTYSK- - -, the same as that of LUCT/IL-8, which is constitutively secreted from lung giant cell carcinoma LU65C cells. The optimal concentration in the chemotactic activity of CT/IL-8, equivalent to that of bacterial chemotactic peptide fMet-Leu-Phe (10 nM), was found to be 5 nM. The results show that this chemotaxin is identical to LUCT/IL-8. PMID- 8344719 TI - A physical map of the human complement component C6, C7, and C9 genes. AB - The genes for human complement components C6, C7, and C9 are linked on chromosome 5. In this report we describe the physical linkage between C6 and C7 genes. DNA fragments obtained by digestion with several rare-cutting restriction enzymes were separated through pulsed field gel electrophoresis. Hybridization with probes corresponding to the 5' and 3' ends of the three cDNAs showed common bands for the C6 and C7 genes. Both genes are contained in a NotI fragment of 500 kilobases (kb). Moreover, the presence of common 3' C6 and 3' C7 fragments indicates that both genes are oriented in a tail-to-tail, reverse way relative to transcription. No evidence of physical linkage between C9 and C6 or C7 was found in the range 50 kb-2.5 megabases (Mb). PMID- 8344718 TI - Phylogeny of immunoglobulin heavy chain isotypes: structure of the constant region of Ambystoma mexicanum upsilon chain deduced from cDNA sequence. AB - An RNA polymerase chain reaction strategy was used to amplify and clone a cDNA segment encoding for the complete constant part of the axolotl IgY heavy (C upsilon) chain. C upsilon is 433 amino acids long and organized into four domains (C upsilon 1-C upsilon 4); each has the typical internal disulfide bond and invariant tryptophane residues. Axolotl C upsilon is most closely related to Xenopus C upsilon (40% identical amino acid residues) and C upsilon 1 shares 46.4% amino acid residues among these species. The presence of additional cysteines in C upsilon 1 and C upsilon 2 domains is consistent with an additional intradomain S-S bond similar to that suggested for Xenopus C upsilon and C chi, and for the avian C upsilon and the human C epsilon. C upsilon 4 ends with the Gly-Lys dipeptide characteristic of secreted mammalian C gamma 3, human C epsilon 4, and avian and anuran C upsilon 4, and contains the consensus [G/GT(AA)] nucleotide splice signal sequence for joining C upsilon 4 to the transmembrane region. These results are consistent with the hypothesis of an ancestral structural relationship between amphibian, avian upsilon chains, and mammalian epsilon chains. However, these molecules have different biological properties: axolotl IgY is secretory Ig, anuran and avian IgY behave like mammalian IgG, and mammalian IgE is implicated in anaphylactic reactions. PMID- 8344720 TI - TAP1 and TAP2 polymorphism in coeliac disease. AB - Coeliac disease is strongly associated with HLA-DQ2, but it is possible that additional major histocompatibility complex genes also confer disease susceptibility. Encoded close to HLA-DQ are two genes, TAP1 and TAP2, whose products are believed to transport antigenic peptides from the cytoplasm into the endoplasmic reticulum. Comparison of 81 coeliac disease patients with caucasoid controls revealed an increased frequency of the alleles TAP1A and TAP2A in the patient population. However, no significant difference was found when patients were compared with HLA-DR and -DQ matched controls, indicating linkage disequilibrium between TAP1A, TAP2A, and HLA-DQ2. The TAP gene products do not have a major influence on susceptibility or resistance to coeliac disease in a Northern European Caucasoid population. PMID- 8344722 TI - Linkage studies between the Tcp-1, Tcp-10, and Mhc-Eqca-A loci in the horse. PMID- 8344721 TI - Sharing of an HLA-B27-restricted H-Y antigen between rat and mouse. AB - The purpose of this work was twofold: 1) to learn whether rats transgenic for HLA B27 and the human beta 2-microglobulin gene HB2M can mount B27-restricted cytolytic T lymphocyte (CTL) responses to the male H-Y antigen, and 2) to learn whether such CTLs would recognize both rat and mouse H-Y in the context of HLA B27. Female rats of the B27/HB2M transgenic line 21-4L were primed in vivo with cells from males of the same line. CTL effectors were generated from lymph node cells of these females following culture with irradiated antigen-presenting cells from either male 21-4L rats or male mice of the B27/HB2M transgenic 56-3 line. The CTLs showed male-specific, B27-specific lysis of both rat and mouse targets. Lysis of B27 targets was inhibitable by monoclonal antibodies specific for B27 or rat CD8. Specific lysis of male B27 rat and mouse targets was inhibitable equally by either rat or mouse male B27 cold targets, but not significantly by female or nontransgenic cold targets. The B27-restricted CTLs neither recognized nor were inhibited by B27+ or B27- male or female human targets. These results demonstrate that CD8+, B27-restricted, anti-H-Y CTLs recognize an evolutionarily conserved H Y peptide antigen in both rats and mice. In addition, they establish the transgenic rat as a model system for examining the T-cell response to antigen presented by class I HLA molecules. PMID- 8344723 TI - A large linkage group on pig chromosome 7 including the MHC class I, class II (DQB), and class III (TNFB) genes. PMID- 8344724 TI - Expression of the Q2 gene of the MHC in thymus and intestinal epithelial cells. PMID- 8344725 TI - Different genomic structure of mouse and human Lmp7 genes: characterization of MHC-encoded proteasome genes. PMID- 8344726 TI - Novel class II HLA-DRB4 and DPB1 alleles found in the Belgian population. PMID- 8344727 TI - Structural polymorphism of six rat RT1Ba genes. PMID- 8344728 TI - Polymorphisms involving the transmembrane domains of human TAP2. PMID- 8344729 TI - Nucleotide sequence of horse beta 2-microglobulin cDNA. PMID- 8344731 TI - Postoperative pulmonary complications in patients with preoperative lung disease. AB - A prospective study was carried out on the incidence of pulmonary complications in 728 patients who underwent major surgical procedures at a reputed hospital in New Delhi. These patients were preoperatively assessed on the basis of history, clinical examination and bedside pulmonary function tests including PEFR, VC, FVC and FEV1. On the basis of these criteria, 212 patients had significant preoperative pulmonary disease, while 516 had normal lung functions. Postoperative pulmonary complications developed in 7.69 per cent of the patients. They were more frequent in smokers (P < 0.001) and in those with preoperative pulmonary dysfunction (P < 0.001). Their incidence was greater following thoraco abdominal and musculoskeletal and miscellaneous operations compared to lower abdominal surgery (P < 0.001). The incidence was also higher following exposure to general anaesthesia compared to regional anaesthesia (P < 0.05). Pneumonia and atelectasis were the most common postoperative pulmonary complications. It was observed that the recovery of pulmonary functions was delayed in patients who developed postoperative pulmonary complications. PMID- 8344730 TI - DNA sequence analysis and polymorphism of the mouse CD4 gene. PMID- 8344732 TI - Immunocytochemical detection of prolactin binding sites in fine needle aspiration smears of breast lesions. AB - Specific prolactin (PRL) binding sites were demonstrated in the fine needle aspiration cytology (FNAC) specimens from 68 patients with benign and malignant diseases of the breast using highly sensitive technique of DNP hapten sandwich staining procedure and antibody against human PRL. In 16 patients, immunocytochemical staining was also carried out on paraffin embedded sections of corresponding lesions. FNAC specimens included 52 neoplasms and 16 non proliferative and proliferative benign breast disease. The reaction varied in different lesions, being maximum (72%) in malignant tumours and 60 per cent in benign tumours. However, benign breast disease showed a reaction that varied with the lesion. The technique was found to be simple, sensitive and economical for demonstrating specific PRL binding sites in cytology specimens of breast lesions. PMID- 8344733 TI - A hospital-based study on the use of paramedical personnel for clinical downstaging of cancer cervix. AB - Two auxiliary nurse midwives (ANMs) were recruited and trained to recognize normal and different types of abnormal cervices. A total of 2102 women were examined by a gynaecologist and ANM independently and their findings were noted. Comparison of their findings showed an overall agreement of 89.6 per cent (Kappa 0.84 with standard error of 0.015 and a significantly large Z value of 55.6). Gross examination of 4679 women attending the Gynaecology OPD revealed normal cervix in 49.6 per cent and suspected lesions or malignant cervix in 3.4 per cent of women. Cytology smears were taken in 3608 women. Adequacy of smears was 97 per cent. Comparing the group clinically diagnosed as highly suspected or malignant to the cytologically diagnosed suspected group (atypical and malignant), clinical examination had a sensitivity of 81.7 per cent and specificity of 97.3 per cent; while comparison of the group clinically diagnosed as abnormal cervix to abnormal cytology (all grades of dysplasia, atypical and malignant cells), the clinical examination had a sensitivity of 92.5 per cent and specificity of 37.4 per cent. It was concluded that paramedical staff (ANMs) can be relied upon to do speculum examination in women in the community and take cytology smears in selected cases. PMID- 8344734 TI - A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure. AB - The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure. PMID- 8344735 TI - Preclinical & pharmaceutical testing of liposomal amphotericin B. AB - Various liposomal amphotericin-B formulations prepared from soya phosphatidylcholine and cholesterol were tested for toxicity, therapeutic efficacy and stability in mice infected with Aspergillus fumigatus. No advantage was noted by removing the unencapsulated drug from that bound to liposomes, as evident by the LD50 and efficacy being similar with both dialyzed and undialyzed formulations. Small unilamellar liposomes were more effective and less toxic, but also less stable, as compared to multilamellar vesicles. In view of these results, multilamellar liposomes were prepared without removing the unencapsulated drug and converted to unilamellar vesicles just prior to administration. The LD50 and efficacy of this formulation was similar to freshly prepared small unilamellar liposomes. These liposomes were prepared under aseptic conditions and were found to be sterile and pyrogen-free. The batch-to-batch variation was also found to be quite low, and therefore liposomal amphotericin B formulation suitable for administration in patients suffering with systemic fungal infection has been developed. PMID- 8344736 TI - Lactose intolerance in idiopathic ulcerative colitis in north Indians. AB - The incidence of lactose intolerance in 60 patients with idiopathic ulcerative colitis (IUC) from northern India and the effect of disease activity and extent of colonic involvement on the occurrence of lactose intolerance, was studied. Twenty controls matched for age and sex were also studied using 50 g lactose hydrogen breath test. The incidence of lactose intolerance in patients with IUC (41.7%) was no different from that in the control group (40%). There was however, a significant difference (P < 0.05) in the incidence of lactose intolerance in patients with active colitis (59.1%) as compared to those with quiescent disease (31.5%). PMID- 8344737 TI - Effect of phenobarbitone on pituitary gland of male albino mice. AB - The effects of phenobarbitone on gonadotrophs and lactotrophs of pituitary gland were studied in male albino mice which were administered phenobarbitone 50 mg/kg body weight intraperitoneally (ip) daily for 14 days. A group of control mice were administered saline ip. In the experimental group, there was significant reduction in the average cell population of FSH cells in the cephalomedian area (P < 0.001) and in the lateral lobe (P < 0.01). The average volume of both FSH and LH cells was also significantly reduced (P < 0.001). The changes in the gonadotrophs of the experimental group could be attributed to the negative feedback action of testosterone which is being secreted from hypertrophied Leydig cells of testis. PMID- 8344738 TI - Evaluation of a modified IRMA for anti-D quantitation, using 3H protein A. AB - A modified immunoradiometry assay (IRMA) using tritiated (3H) protein A was developed to estimate anti-D concentration. The main advantages of the assay were longer shelf life of the labelled reagent (more than two years); minimum radiation hazard and; low non specific binding. Levels of anti-D were estimated in 23 Rh (D) immunised women. A good correlation of anti-D concentration (micrograms/ml) with Rh antibody titre was observed (r = +0.89, P < 0.01). Anti-D concentration estimated by 3H protein A IRMA correlated well with the severity of Rh-HDN. This assay could quantitate anti-D in sera having exclusively IgG3 subtype. PMID- 8344739 TI - Changing profile of haematogenous osteomyelitis in a teaching hospital. AB - A total of 155 consecutive patients of osteomyelitis were studied clinically, radiologically and bacteriologically. The follow up ranged from 2 1/2 to 4 1/2 yr (average 3.5 yr). Age varied from 8 months to 50 yr. Onset of the disease was acute in 106 and insidious in 49 patients. Of these 116 cases were treated conservatively which include 12 treated by incision and drainage. The rest underwent surgery (saucerization, curettage, sequestrectomy etc.). There was a trend for osteomyelitis to shift from the known incidence in early age to adulthood, acute to insidious onset and infection by Gram positive to Gram negative organisms. PMID- 8344740 TI - Effect of tri-ortho-cresyl phosphate on hen nervous system. AB - Correlation of tri-ortho-cresyl phosphate (TOCP) toxicity with clinical symptoms and inhibition patterns of neurotoxic esterase (NTE) in different regions of the central nervous system was studied in hens. The total content of NTE in spinal cord and peripheral nerves was relatively much lower than that of the brain, about 29 and 4.8 per cent respectively. Brain and spinal cord NTE was inhibited to 75 and 67 per cent respectively on day 1 post-TOCP treatment, and 91 and 84 per cent respectively on day 2, while the activity of the enzyme in peripheral nerve was inhibited to 92 per cent on day 1. However, the clinical manifestations of paralysis appeared after 7-8 days of TOCP treatment. It can be concluded that the presence of NTE in very low quantities in the peripheral nerves and its almost complete inhibition as compared to that of brain and spinal cord, could be of great significance in the development of neurotoxicity. PMID- 8344741 TI - From adjuvant to neo-adjuvant chemotherapy in high-risk breast cancer: the experience of the Milan Cancer Institute. Steiner Award Lecture 1992. PMID- 8344742 TI - Altered expression of basement-membrane components and collagenases in ascitic xenografts of OVCAR-3 ovarian cancer cells. AB - Ascitic ovarian cancer cells, which derive from solid tumors, complicate the treatment of ovarian cancer by spreading throughout the peritoneal cavity. Because basement-membrane components may influence tumor-cell proliferation and dissemination, the present studies examined the production of (a) basement membrane attachment and migration factors (laminin, fibronectin and type IV collagen); (b) a laminin receptor, the 32/67-kDa laminin-binding protein, the presence of which correlates with malignancy; and (c) metalloproteinases (types I and IV collagenase and stromelysin), by ascitic and cultured OVCAR-3 cells and solid OVCAR-3 tumors. The cultured cells and solid tumors produced high levels of mRNA encoding attachment factors and metalloproteinases, and low levels of mRNA for the 32/67-kDa laminin receptor. In contrast, the ascitic ovarian cells had low or undetectable levels of mRNA encoding laminin, type IV collagen and metalloproteinases, but higher levels of transcripts for the laminin receptor. Our results suggest that the apparent inability of ascitic OVCAR-3 cells to attach to host-tissue surfaces may be a consequence, in part, of low levels of expression of laminin, type IV collagen and/or type IV collagenase. PMID- 8344743 TI - Modification of TNF-alpha pharmacokinetics in SA-1 tumor-bearing mice. AB - Fibrosarcoma-SA-I-tumor-bearing mice were treated s.c. in the vicinity of tumors (peri-tumorally) or intravenously, with recombinant human TNF-alpha lacking 1 to 3 amino acids from N-terminal part (TNF-alpha Nv3). Tumor growth delay, observed after both routes of TNF-alpha Nv3 application, was statistically significant, though a better anti-tumor effect was achieved after peri-tumoral application. TNF-alpha Nv3 serum levels were determined in these animals and compared with TNF alpha Nv3 serum levels in healthy animals, which were treated with TNF-alpha Nv3 either s.c. or i.v. The peak serum levels of TNF-alpha Nv3 applied peri tumorally/s.c. were significantly higher in tumor-bearing than in healthy mice, whereas smaller differences in peak serum levels were found after i.v. application, which might correlate with anti-tumor activity. Whatever the route of application, TNF-alpha Nv3 elimination from the serum of tumor-bearing mice was slower than that in healthy animals. Also, comparison of TNF-alpha Nv3 pharmacokinetic parameters for tumor-free and sarcoma- or melanoma-bearing mice has demonstrated that the pharmacokinetics of TNF-alpha Nv3 are modified in tumor bearing animals. PMID- 8344744 TI - Analysis of production, purification, and cytolytic potential of bi-specific antibodies reactive with ovarian-carcinoma-associated antigens and the T-cell antigen CD3. AB - OV-TL3 and MOv 18 MAbs, due to their restricted specificity, have been successfully used to visualize ovarian cancer in patients and might therefore be used to develop therapies for ovarian cancer. The bi-specific MAbs alpha T3/OC2 and alpha OC/TR (both being combinations of MOv18 and alpha CD3) have been shown to lyse ovarian tumor cells in vitro. To evaluate the relative merits of MOv18/CD3 and OV-TL 3/CD3, the present study was undertaken in which the bi specific MAbs alpha T3/OC2 and alpha OC/TR, and a newly developed bi-specific MAb, OV-TL 3/CD3, were highly purified and compared for specificity, stability, purification and cytolytic potential. The dual specificity of the hybrid hybridoma supernatants was analyzed by immunohistochemistry, and by testing bi specific MAb-mediated cytotoxicity against relevant target cells in the presence of effector cells. Stability testing of bi-specific MAb-producing hybridomas showed that, after sub-cloning, clones stably produced up to 40% bi-specific MAb even after prolonged in vitro culture. The purification of the bi-specific fractions was performed with protein A and by ion-exchange high-pressure liquid chromatography, depending on the sub-class combination of the bi-specific MAb. The purified bi-specific MAbs were tested for their ability to mediate target cell lysis with the use of cytotoxic T-cell clones and activated peripheral-blood lymphocytes. The purified alpha T3/OC2, alpha OC/TR, and OV-TL3/CD3 were all able to mediate highly specific lysis of various ovarian-carcinoma cell lines. No correlation was found between the level of antigen expression and bi-specific MAb mediated cytolysis. PMID- 8344745 TI - Cytokines as adjuvants: effect on the immunogenicity of NeuAc alpha 2-6GalNAc alpha-O-Ser/Thr (sialyl-Tn). AB - Sialyl-Tn, defined by monoclonal antibody (MAb) B72.3, shows restricted normal tissue distribution but is expressed in a wide variety of carcinomas. To analyze the immunogenicity of sialyl-Tn, mice were immunized with ovine submaxillary mucin (OSM) in combination with monophosphoryl lipid A (MPLA), liposomes, or adjuvants that activate macrophages (rIL-1, rIFN-gamma, rM-CSF, IL-1-derived peptides) or T cells (rIL-2). The level and specificity of the immune response were analyzed by ELISA. rIL-1 and rIFN-gamma induced a very high and specific antibody response, whereas the effect of rM-CSF was dose-dependent: at a low dose it induced a high-level specific antibody response and at the high dose level it induced a polyclonal non-specific response. These results indicate that cytokines are powerful adjuvants which modulate both the magnitude and specificity of the immune response. More studies are necessary to determine the optimal doses in animal models and in active specific immunotherapy of patients with cancer. PMID- 8344746 TI - Complete local tumor remission after therapy with extra-corporeally applied high energy shock waves (HESW). AB - High-energy shock waves (HESW) have recently been proposed as a means of non invasive tumor therapy. Here we report the first successful local treatment of experimental tumors by means of multifocal and reported application of HESW. The experiments were performed on 29 Syrian golden hamsters bearing amelanotic hamster melanomas in the dorsal skin. HESW, generated electrohydraulically, were applied multifocally to the center and to 5 sites on the margin of the tumors. A group of animals undergoing surgical resection and an untreated group served as controls. Complete remission of local tumor was achieved in more than 90% of the HESW-treated hamsters and in the same number of surgically treated animals, while untreated tumors continued to grow. Frequency of metastasis was the same in both groups after HESW treatment or surgery. Tumor therapy with multifocally and repeatedly applied HESW was thus as successful as surgery. PMID- 8344747 TI - Human melanoma cells express a functional interleukin-2 receptor. AB - Flow cytometric analysis reveals that 5 human melanoma cell lines (M14, IGR3, ME1477, JUSO, GLL19) express both alpha and beta chain of the interleukin 2 receptor (IL-2R alpha and IL-2R beta). These chains are able to specifically bind IL-2 and to form high-affinity heterodimers (IL-2R alpha beta). Analysis of poly A+ RNAs by Northern blot reveals the presence of typical transcripts for both the IL-2R alpha gene (3.6 kb) and the IL-2R beta gene (4 kb). Reverse transcription/polymerase chain reaction analysis allowed transcripts for the IL2R gamma (p64) gene to be detected in 3 of these melanoma cell lines (M14, IGR3, ME 1477). Incubation with human recombinant IL-2 modifies in IL-2R alpha+beta+gamma+ (M14) the expression of several surface molecules: down-regulation of ICAM-1, HLA class I and HLA-DR and up-regulation of CD44. IL-2 is also active on IL-2 alpha+beta+gamma- cell lines since it decreases ICAM-1 and HLA class-II expression at the surface of JUSO cells. Down-regulation of ICAM-1, whose expression in melanoma cells is a marker of tumor progression, is detectable within 3 hr in M14 cells and is maximal after 48 hr incubation, at IL-2 concentrations corresponding to the high-affinity heterodimers. This feature is specific since it is partially inhibited by MAbs directed against the IL-2 binding site of the IL-2R alpha (MAR93, 10T14) and IL-2R beta (MiK beta 1, TU27) chains. Our data support the notion of a direct effect of IL-2 on human melanoma cells. Modulation of the expression of surface molecules which is important for the interaction with immunocompetent cells or for tumor progression, could have a role to play during in vivo IL-2 treatment of human melanomas. PMID- 8344748 TI - Enhanced expression of a tumor-cell-derived collagenase-stimulatory factor in urothelial carcinoma: its usefulness as a tumor marker for bladder cancers. AB - A mouse monoclonal antibody (MAb) E11F4, previously raised against the tumor-cell derived collagenase-stimulatory factor (TCSF) from LX-1 human lung-carcinoma cells, has been used to define the expression and distribution of TCSF in human non-neoplastic urothelium and tumors of the urinary bladder. Immunohistochemically, TCSF was detected in 27/28 transitional-cell carcinomas (TCC) of the bladder, of which 23 were judged to be positive for TCSF according to objective criteria. Twenty-four of 28 non-neoplastic urothelium from 22 individuals were judged to be negative for TCSF by this criteria. However, TCSF immunostaining that was confined to the superficial umbrella cells was frequently observed in non-neoplastic urothelium. In bladder carcinomas, TCSF was in most cases demonstrated in the majority of cells, including at the invasion front. Its localization to the cell membrane was demonstrated by immunoelectron microscopy. The high level of expression of TCSF in bladder tumors, but not in non-neoplastic urothelium, was also demonstrated by immunoblotting of tissue extracts. Furthermore, E11F4 immunostaining identified tumor cells obtained from bladder washings or voided urine and detected more TCC cases than conventional cytology. Since TCSF immunostaining was positive even in low-grade TCC (immunohistochemically and immunocytochemically in 4/5 TCC grade I), the application of TCSF immunostaining to urine cytology appears promising as a valuable adjunct to conventional methods in the clinical evaluation of patients with TCC. PMID- 8344749 TI - The plasminogen-activation system in ovarian tumors. AB - We studied the plasminogen activation system in tumor tissue by measuring the antigen level of the 2 plasminogen activators, tissue-type (t-PA) and urokinase type (U-PA) and their inhibitors, plasminogen-activator inhibitors type-I (PAI-I) and type-2 (PAI-2) in the tissue extracts of 43 human benign and malignant ovarian tumors. U-PA levels were significantly higher in malignant than in benign tumors. In addition, U-PA antigen levels were higher in the metastatic tissue of advanced disease (FIGO stage III) than in the primary localized tumor (FIGO stage I/II). Also PAI-I concentrations tended to be higher in malignant than in benign tumors, but this difference was not statistically significant. In contrast, t-PA levels were lower in metastatic than in non-metastatic tumors, whereas PAI-2 levels were unrelated to the stage of ovarian malignancy. These results were integrated in a plasminogen-activation-dependent malignancy index (U-PA x PAI-I/t PA). This index distinguished the different groups of benign ovarian tumors, localized and metastatic ovarian carcinomas better than U-PA levels. It could be useful as a prognostic indicator in ovarian cancer. PMID- 8344750 TI - Risk factors for renal-cell carcinoma in a French case-control study. AB - A hospital-based case-control study of renal-cell carcinoma was conducted in France from 1987 to 1991. A total of 196 histologically confirmed cases (138 males and 58 females) and 347 controls (235 males and 112 females), matched for sex, age at interview, hospital and interviewer, were included. The risk of renal cell carcinoma was not apparently increased with number of cigarettes per day, duration of smoking or early age at first cigarette smoking in males. No significant trend was found in the risks with increasing Quetelet index (QI) at the age of 20 in males. On the contrary, the risks increased significantly with an increasing QI prior to diagnosis. In females, the trends in risks were significant both for the relative weight at the age of 20 and prior to diagnosis. The consumption of regular or decaffeinated coffee, tea or alcoholic beverages was not associated with renal-cell carcinoma, in males or in females. PMID- 8344751 TI - Cytogenetic findings in 33 osteosarcomas. AB - Thirty-three osteosarcomas (OS) were analyzed cytogenetically. Clonal chromosome changes were detected in 17 cases. Six tumors had chromosome numbers in the diploid range, 6 in the triploid range, 1 in the tetraploid range and 1 in the pentaploid range, while 3 tumors had multiple clones with different ploidy levels. Including the present 17 tumors, a total of 27 OS with clonal aberrations have been reported. The recognizable structural rearrangements in these 27 tumors clustered to chromosome arms 1p, 1q, 3p, 3q, 7q, 11p, 17p and 22q. Chromosome bands 1q11, 1q21, 1q42 and 7q11 were the most frequently rearranged, and the most common numerical rearrangements were -3, -10, -13 and -15. Supernumerary ring chromosomes, in 2 tumors as the sole change, were found in all 3 parosteal OS, which is in agreement with the findings in 1 previously reported parosteal OS. The association between ring formation and parosteal morphology represents the first cytogenetic-morphologic entity among OS. PMID- 8344752 TI - Risk of kidney cancer among patients using analgesics and diuretics: a population based cohort study. AB - The aim of this study was to determine the risk of kidney cancer in 2 cohorts defined on the basis of hospital discharge diagnoses associated with analgesic or diuretic use during the period 1965 to 1983. Patients were followed up through 1984 for cancer incidence. After excluding cancers in the first year of observation, 161 kidney cancers were observed vs. 138 expected among 54,662 patients in the analgesics cohort. The relative risk was higher for women than for men. When examined by sub-site within the kidney, risk for cancer of the renal pelvis was similar in magnitude to that for the renal parenchyma. Among 115,616 patients in the diuretics cohort, 278 kidney cancers occurred vs. 209 expected. The risk for women was higher than for men. This elevation in risk was confined to cancer of the renal parenchyma, with no significantly increased risk seen for cancer of the renal pelvis. Although we observed little excess risk among members of the analgesics cohort, the significantly elevated risk among patients using diuretics supports a number of recent studies, but inability to adjust for confounding factors such as obesity preclude drawing any conclusion regarding diuretics. Further research is warranted to assess in detail the relationship between diuretic use and cancer of the renal parenchyma. PMID- 8344753 TI - p53 protein expression in breast cancer as related to histopathological characteristics and prognosis. AB - Formalin-fixed, paraffin-embedded biopsies of 193 women with primary breast cancer followed-up for over 10 years were analysed immunohistochemically for the expression of p53 protein. Altogether, 58% (113/193) of the tumors were positive for p53 protein. Over-expression of p53 was associated with the ductal type, high grade tumors, dense stromal inflammatory cell infiltrate, high S-phase fraction, high mitotic frequency and high values of the nuclear factors. In univariate analysis, intense p53 over-expression predicted a poor outcome, whereas a short recurrence-free survival (RFS) was related to p53 negativity. In axillary lymph node-negative (ANN) tumors, p53 negativity was related to short RFS, and in axillary lymph-node-positive (ANP) tumors this inverse relationship was statistically significant. In Cox's analysis, p53 protein over-expression had no independent prognostic value comparable with the well-established prognostic factors. However, p53 protein accumulation was an independent indicator of long RFS in the entire cohort, in ANP tumors and in rapidly proliferating tumors. The results indicate a dual role for p53 protein over-expression in breast cancer prognosis. The low survival probability associated with intensively p53-positive tumors is probably related to rapid cancer-cell proliferation, whereas the long RFS of p53-positive tumors might be explained by the development of circulating antibodies to p53 protein. The role of p53 protein in breast cancer is incompletely understood, and the p53 gene should be subjected to detailed analysis of specific mutations. PMID- 8344754 TI - Cancer among teenagers in Denmark, 1943-1987. AB - A population-based study was carried out on 3,988 tumours in teenagers (aged 10 19 years) diagnosed during the period 1943-87 in Denmark and abstracted from the files of the National Cancer Registry. In that Registry, codes for tumours were based solely on topography until the end of 1977. In order to obtain a uniform data set, coded by the system of the International Classification of Diseases for Oncology (ICD-O) now used at the Cancer Registry, all cases of teenage cancer diagnosed prior to 1978 were re-evaluated, and an ICD-O code was applied. Tumours were further aggregated into diagnostic groups using an internationally agreed scheme. The average incidence rates for all histological types combined were 136 per million for boys and 108 per million for girls, which are close to those reported in Connecticut, USA. Central nervous system tumours, leukaemia and malignant lymphomas accounted for 60% of all cancers among teenagers. An overall excess of cancers among boys was mainly due to more frequent occurrence of leukaemias, malignant lymphomas, sarcomas and germ-cell tumours. Increasing trends with time were seen for malignant lymphomas in both boys and girls and for subtypes of non-seminoma germ-cell tumour among boys aged 15-19. For other diagnostic groups, including the main group of leukaemias, the rates have remained largely unchanged, suggesting that environmental factors associated with modern society play a minor role in the aetiology of cancer among teenagers. PMID- 8344755 TI - Aberrant expression of c-met mRNA in human gastric carcinomas. AB - We examined mRNA expression for c-met encoding hepatocyte growth factor receptor in 8 gastric carcinoma cell lines and 31 surgically resected gastric carcinoma tissues by Northern-blot analysis. Two forms of the transcript, sized 7.0 kb and 6.0 kb, were found in gastric carcinomas. Transcripts of both sizes were detected at various levels in all the gastric carcinoma cell lines except the MKN-74 line, which expressed only the 7.0-kb form. Of the 31 gastric carcinomas, 15 (48%) over expressed the 7.0-kb transcript when compared with non-neoplastic mucosa. The 6.0 kb transcript of the c-met gene was expressed at considerable levels in 52% of the gastric carcinoma tissues, whereas it was only slightly expressed in non neoplastic mucosa of a small number of cases. An important finding was that expression of the 6.0-kb transcript was closely correlated with tumor staging, lymph-node metastasis and depth of tumor invasion. These results, overall, suggest that the 6.0-kb transcript of the c-met gene might participate in the development and progression of gastric carcinomas. PMID- 8344756 TI - Cytotoxicity, differentiating activity and metabolism of tiazofurin in human neuroblastoma cells. AB - The IMP dehydrogenase inhibitor, tiazofurin (TR)-2-beta-D-ribofuranosylthiazole-4 carboxamide, which exhibited oncolytic activity in patients with chronic myelogenous leukaemia (CML) in blast crisis was found to inhibit the growth of human neuroblastoma SK-N-SH cells with an IC50 of 4.2 microM. TR treatment of cells perturbed nucleic acid and catecholamine pathways. As biochemical markers of TR action decreased cellular GTP pools, increased inosine and hypoxanthine concentrations and depleted dopamine content were found. Incubation of tumour specimens obtained from paediatric patients with grade-IV neuroblastoma with TR resulted in the formation of the active metabolite, thiazole-4-carboxamide adenine dinucleotide, in concentrations sufficient to inhibit tumour growth. Cytotoxic and biochemical effects of TR were enhanced by combining it with allopurinol (an inhibitor of xanthine dehydrogenase), and hypoxanthine (an alternate substrate for hypoxanthine-guanine phosphoribosyltransferase). Induction of transdifferentiation of SK-N-SH cells from a neuroblast to an epitheloid, substrate-adherent phenotype was more pronounced with TR than with all-trans-retinoic acid. Transdifferentiating treatment with TR resulted in a 2 fold-enhanced sensitivity towards adriamycin. However, differentiation with all trans-retinoic acid rendered the cells more resistant to adriamycin. Our results suggest that TR might be a promising agent for the treatment of children suffering from neuroblastoma. PMID- 8344757 TI - Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin-6 expression. AB - Recent data indicate a major role for IL-10 in suppressing immune and inflammatory reactions. To date, expression of human IL-10 has been attributed primarily to helper T lymphocytes, activated monocytes, and neoplastic B cells, and was often found to be associated with IL-6 expression. In this study we sought to determine whether non-hematopoietic human tumor cell lines produce IL 10 and, if so, what is the relationship between IL-10 and IL-6. Using ELISA, we determined IL-10 and IL-6 levels in culture supernatants of 48 cell lines established from carcinomas of the kidney, colon, breast and pancreas, malignant melanomas and neuroblastomas. IL-6 protein was secreted by 28 of the tumor cell lines; IL-10 was measurable in 15 cell lines. IL-6 secretion was maximal and most frequent in renal-cancer cell lines, while IL-10 production was found to be highest and most common among cell lines derived from colon carcinomas. IL-10 in conditioned medium of one of the colon carcinoma cell lines (CCL222) was bio active, as demonstrated in the mouse MC/9 mast-cell-line assay and in human mixed lymphocyte reactions. In both assays, IL-10 bio-activity was neutralized by an anti-IL-10 monoclonal antibody. Expression of IL-6 and IL-10 was confirmed by RNA analysis using message amplification by PCR and sequencing of amplified cDNA. LPS, IL-1 alpha, and TNF-alpha strongly enhanced the release of IL-6 by RCC cells, but only marginally affected IL-10 production in colon-carcinoma cells. IL 10 secretion by colon-carcinoma cells was moderately stimulated by IFN-gamma and IL-4. Dexamethasone suppressed the release of IL-6, but had no inhibitory effect on IL-10 secretion. Our results demonstrate that tumor cell lines established from certain types of human carcinomas are capable of expressing and releasing IL 6 and/or IL-10, suggesting a role of these cytokines in solid-tumor development and anti-tumor immunity. PMID- 8344758 TI - Endocervical glandular atypia and adenocarcinoma: a correlation of cytology and histology. AB - Of the 34,384 cervical smears sampled by cervical scraping and Cytobrush, reactive glandular atypia was found in 1.7%, low-grade glandular atypia in 0.08%, and high-grade glandular atypia/adenocarcinoma in 0.05%. Cells of reactive glandular atypia and low-grade atypia could be distinguished from those of high grade atypia/adenocarcinoma by the architecture of the cellular aggregates, nuclear morphology, and nuclear-cytoplasmic ratios. Further histologic studies found that most reactive and low-grade atypias were associated with condyloma, squamous dysplasia, carcinoma in situ, and cervicitis. Eighty-two percent of women with cellular evidence of high-grade atypia/adenocarcinoma were confirmed to have in situ or invasive adenocarcinoma of the cervix. Although Cytobrush samples seem to improve the detection of early-stage glandular neoplasms, many minor atypias unrelated to cervical carcinogenesis are also detected. PMID- 8344759 TI - Multinucleated stromal giant cells of the uterine cervix. AB - A prospective clinicopathological study including 100 consecutive hysterectomies and 100 consecutive cone specimens to investigate the frequency and pathogenesis of multinucleated stromal giant cells (SGCs) in the uterine cervix is presented. Sections containing SGCs were analyzed by immunohistochemical methods for the presence of cytokeratin, S-100 protein, factor VIII, desmin, muramidase, alpha 1 antichymotrypsin, and vimentin. Tissue for electron microscopy was punched out of four paraffin blocks from four different cases. SGCs were not found in patients < 30 years old, but their incidence increased with age until the sixth decade, at which time they were found in 42% of patients. We found at the same time that the incidence of SGCs declines in the seventh decade. SGCs were not related to any inflammatory or granulomatous lesion, and their presence was independent of other clinical parameters, such as hormonal therapy, history of trauma on the uterine cervix, pregnancy, or parity in general. Immunohistochemical and ultrastructural analyses support the concept of a fibroblastic-histiocytic origin of SGCs. SGCs in the uterine cervix may reflect a physiological tissue reaction during the transition from the fertile to the postmenopausal state. PMID- 8344760 TI - Flow cytometric DNA ploidy and quantitative histopathology in partial moles. AB - This study quantitates morphologic changes seen in partial moles and hydropic abortuses in an attempt to find a correlation with DNA content. Thirty-two products of conception were studied. Fifteen were diagnosed as definitive partial moles (DPM), and 17 had changes suggestive of a partial mole (SPM). We determined DNA ploidy by flow cytometry and quantitatively analyzed the following microscopic features: villous edema and sclerosis, central cistern formation, villous blood vessels, trophoblastic proliferation, and trophoblastic inclusions. No single pathologic feature significantly correlated with DNA content, even though triploid cases showed more inclusions than diploid cases (8.3 versus 7.2 on the average per ten x 100 fields). An overall diagnosis of DPM did correlate with ploidy; 12 of 18 triploid cases (67%) compared with only three of 13 diploid cases (23%) had been previously diagnosed as DPM (p < 0.05). Flow cytometric DNA ploidy estimates DNA content and cannot determine chromosomal origin. It is possible that detailed cytogenetic studies of moles compared with abortuses may show a significant correlation of the proportion of paternal chromosomes, morphologic changes, and the risk of persistent gestational trophoblastic disease. PMID- 8344761 TI - Expression of epidermal growth factor receptors in human endometrial carcinoma. AB - Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous hyperplasia. EGF R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent at the cell membranes, with a varying pattern in individual carcinomas. EGF-R expression was not correlated with histologic grade, surgical stage, or estrogen/progesterone receptor status evaluated immunohistochemically or biochemically in adjacent tissue sections of the tumor. Ten of 13 (77%) atrophic/inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas. PMID- 8344762 TI - Use of monoclonal antibodies MSN-1 and B72.3 in the prediction of the natural history of endometrial hyperplasia. AB - Forty patients, originally diagnosed as endometrial hyperplasia, were reviewed histopathologically and evaluated for immunohistochemical staining with antibodies directed against TAG-72 and MSN-1 antigens. All patients had follow-up endometrial biospies or hysterectomies from 1 to 13 years later. The extent of regression to normal of nonhyperplastic endometrium, persistence as any type of endometrial hyperplasia, or progression to endometrial adenocarcinoma was correlated with the histologic hyperplastic subtype and immunohistochemical staining. As expected, cases of complex or atypical hyperplasia more often progressed to carcinoma than cases of simple or no hyperplasia. Interestingly, MSN-1 positivity was more prevalent in cases of higher grades than lower grades of hyperplasia and was associated with the tendency to show persistent hyperplasia or progression to carcinoma. B72.3 positivity was uncommon in the hyperplastic endometrium and was not correlated with clinical regression or progression. Although the tendency for progression of endometrial hyperplasia to endometrial carcinoma is best judged histologically, MSN-1 may add prognostic information in subgroups of hyperplasia. PMID- 8344763 TI - Prognostic significance of nucleolar organizer regions in ovarian epithelial tumors. AB - Recent studies have shown that the silver-stained nucleolar organizer region (AgNOR) score is related to the cell growth rate in several neoplasms. In the work presented here, we tested the AgNOR technique in 79 ovarian epithelial tumors (13 benign, 10 borderline, 56 malignant) to evaluate the diagnostic potential of AgNOR count in distinguishing between ovarian borderline tumors and carcinomas and to assess its prognostic value in carcinomas. Ovarian carcinomas exhibited higher mean AgNOR values than borderline and benign tumors, but statistically significant differences were found only in the serous type. Statistical analysis showed a positive correlation of higher AgNOR score, advanced tumor stage, and adverse prognosis. On the contrary, low AgNOR counts identified stages I and II carcinomas with disease-free follow-up. These results suggest that the AgNOR count may improve the prognostic evaluation of ovarian epithelial tumors by representing a reliable indicator of survival. PMID- 8344764 TI - Primitive neuroectodermal tumor arising in an ovarian mature cystic teratoma: immunohistochemical and electron microscopic studies. AB - The occurrence of a malignant neuroectodermal tumor in a mature cystic teratoma is extremely rare. Five cases of ovarian primitive neuroectodermal tumors (PNET) or neuroepitheliomas have been reported. In two, the tumor was adjacent to foci of a mature teratomatous element. We present the immunohistochemical profile and electron microscopic study of an ovarian mature cystic teratoma with PNET or malignant neuroepithelioma. The transition between the mature neural elements and the malignant PNET presents a model for monodermic neuroepithelial differentiation and explains the histogenesis of this unusual tumor. PMID- 8344765 TI - Cytogenetic analysis of an immature teratoma of the ovary and its metastasis after chemotherapy-induced maturation. AB - We report a case of an immature teratoma of the ovary, grade 3, in which cytogenetic studies were performed on the primary tumor at diagnosis and on a metastasis resected 1 year after removal of the primary tumor. The patient was treated with cisplatin, bleomycin, and etoposide (VP-16) combination chemotherapy. The metastatic tumor was composed of mature teratoma with only small foci of immature tissue. Despite the different histologic appearance of the primary tumor and the metastasis, there was no detectable difference in karyotype between the primary and metastatic tumors. Both showed a pseudodicentric chromosome derived from chromosome 1 and monosomy for chromosome 4. Flow cytometry analysis of the metastatic tumor showed a diploid DNA content, in agreement with the cytogenetic findings. From this case it would appear that chemotherapy-induced maturation of metastatic immature ovarian teratoma is not associated with regression of the malignant karyotype or selection of a karyotypically distinct population of tumor cells. PMID- 8344766 TI - On the drive-rootedness of psychoanalytic ego psychology. AB - This paper attempts, hypothetico-deductively, to conceptualise psychoanalysis on the level of fundamental theory. I begin by exploring the relevance for psychoanalytic theory of recent developments in the brain and cognitive sciences. Their site of articulation is identified as the concept of consciousness. I proceed to develop a conceptual integration of consciousness into psychoanalytic drive theory. This reveals the wish as the original psychical entity, with a self process imbricated in its structure. Narcissism in shown to be sexually grounded, vitally constitutive, and intrinsically aggressive. It becomes possible, using the neighbouring sciences as well, to work out a theory of the origin of the secondary process and early ego formation. My approach provides a view of mental development in which identification and repression represent two aspects of a unitary activity that structures the mind. This allows the unconscious and consciousness to be brought into dialectical relation. Implications follow for the 'activity of the repressed' and the theory of paranoia. PMID- 8344767 TI - The complementarity of object-relations and instinct theory. AB - Object-relations theory implicitly assumes primary drives to cope with the fact that some kinds of transaction with objects are not gratifying but are feared and avoided. Fairbairn's conception of motivation assumes that there is an independent primary drive which may be called 'need for love', independent of other gratifications. Such an instinctual-drive concept is defined solely by its direction towards a goal, and rests on an arbitrary intuition as to the 'real' goal of observed behaviour. As Freud pointed out, what is required for the objective identification of a drive is the discovery of its physiological source. Freud recognised that a drive can be gratified only by a 'specific action' performed upon a suitable object, and that object relations set up in very early life are especially long-lasting. The concept of fixation can bridge the gap between infantile instinctual reactions and adult object relations. PMID- 8344768 TI - Aggression and the psychological self. AB - In this paper we explore the idea of aggression as a defence against threats to the psychological self. This aspect of the self allows reflection about people in psychological terms and develops, in the first three years of life, through appreciation of mental states in the other. When the object is unpredictable or hostile, recognition of this is painful to the child, and his reflective function will not be adequately established. The defences of aggression or avoidance will be invoked very frequently. In time, aggression may become an organising influence in the construction of the self; pathological destructiveness then takes the place of emotional relatedness and concern for the other. Psychoanalytic treatment no longer works primarily by addressing conflict. Instead, particularly through interpretations of transference and countertransference, the analyst recreates an intersubjective process which enhances the patient's reflective self, this time in the safety of a benign relationship. PMID- 8344769 TI - A fundamental dilemma of psychoanalytic technique: reflections on the analysis of a perverse paranoid patient. AB - The work refers to the general topic of the traumatic effects of transference in the analytic situation. The author defines the fundamental dilemma of interpretive technique as the technical difficulty, sometimes insurmountable, faced by the therapist in the treatment of severely ill patients, particularly in the case of narcissistic, self-centred disorders, where the interpretive action itself often produces negative side effects that are not countered by the curative effect of the insight achieved through interpretation. In a brief theoretical introduction, this dilemma is described as a longstanding problem in psychoanalysis that has been systematically concealed by the protracted discussion on the subject of 'analysability' and which has still not been resolved by the theory of technique. Clinical case material on a perverse patient is then presented to illustrate the dilemma described and to demonstrate some general strategies by which it may be overcome. PMID- 8344770 TI - A self-psychological approach to the analysis of resistance: a case report. AB - This paper attempts to explore the understanding of resistance from a self psychological perspective through presenting a case report. This view is contrasted to the traditional psychoanalytic model which assumes that whatever impedes the analysis is a resistance, and construes such resistance in terms of the drive-defence model. The motivation for this blockade of the analysis is the protection of the ego from anxiety. By contrast, a self-psychological model suggests that 'so called defence-resistances' (Kohut, 1984, p. 141) are required for the protection of the weakened self. There is no blockade of the analytic process; rather, the 'resistance' safeguards the self so that the analysis may continue. The motivation for 'resistance' is to protect the self so that it will be ready to resume development when a safe, attuned selfobject environment is available. In the case presented the patient beseeched the analyst to refrain from speaking. The analyst's dilemma is discussed and the resolution of the resistance is described. PMID- 8344772 TI - First person personal pronouns and their psychic referents. AB - This paper presents a psychoanalytic description of the psychic referents for the personal pronouns I, me, myself. The referents are related to memorial processes of experiences of satisfaction is early bodily dialogues. Later interpersonal dialogues, bodily and verbal, factual or fantazised, add to the memories available as potential referents for the pronouns. The linguistically spoken pronoun has a narrower referential field because a speech act can only tap a limited number of memories. The 'I'/'me' of each spoken sentence is a selected libidinal and narcissistically organised self-perception at the service of an exchange with the interlocutor at hand, the specific 'you' of that linguistic act. The linguistic 'I' is a transient pronominal function linked to memories about oneself and others. It reveals in the selection of referential sources, libidinal and narcissistic regulatory functions in the service of satisfaction of wishes, defence, and modulation of self-esteem. PMID- 8344771 TI - Phallic patheticness. AB - The characteristic of patheticness in the case of a young female victim of child abuse has been presented, underscoring the phallic quality of this trait and its root distinctiveness from the tragic character. Many patients, historical figures, and other individuals are prematurely judged as tragic when, in fact, we are reacting uncritically to the impact of their profound patheticness, at a point when, more often than not, such patheticness has not yet reached its lowest ebb, when it is still not too late to transform mute resignation to the neurosis of tragic fatalism into a more heroic deployment of destiny (Bollas, 1991, pp. 31 4). Phallic patheticness, in fact, represents a higher psychical achievement by virtue of its transient quality and its propensity to enable basic, if conflictual object-relationships and the recovery from psychic trauma. To be sure, many individuals with advanced personality structures have introjected into their personal value system a sense of the tragic, an identification with the tragic, or a special proclivity toward the tragic aspects of life, but this in and of itself does not render such individuals tragic, nor do they typically evoke in others the inner experience of maximum catastrophe or calamity. It is argued that the distinction between pathetic and tragic psychic structure can be clarified through carefully interpreted counter-transference. PMID- 8344773 TI - Adequate distance in the relationship between supervisor and supervisee. The position of the supervisor between 'teacher' and 'analyst'. AB - Supervision, being at the centre of our tripartite psychoanalytical training, imposes on the supervisor an extremely important, complex and difficult task. Supervision is central in the training of the future psychoanalyst because the outcome of the supervisory process will eventually be an internalisation of the supervisor's functioning, and this inner functioning of the internalised supervisor will be crucial for the competent functioning of the candidate as future psychoanalyst. This complex and difficult learning process will be best fostered if the supervisor permanently strives to maintain his supervisory balance between the two supervisory positions he is to take in the supervisory process, that between 'teacher' and 'analyst'. This paper tries to demonstrate both positions in this process and to discuss problems of how to maintain them; and how to re-establish the supervisor's balance, and with it, the adequate psychoanalytic distance in supervision in situations where they tend to get lost. PMID- 8344774 TI - The illusion of a future: a friendly disagreement with Prof. Sigmund Freud. AB - Freud's The Future of an Illusion was not just an abstract statement of his position on religion, but part of an ongoing exchange of views with Oskar Pfister, a Zurich pastor. Freud was continuing to try to settle differences between himself and Jung. Pfister, while practising as an analyst in 1928, wrote a respectful reply to Freud, and his 'The Illusion of a Future' has never before appeared in English. Pfister was expressing what he saw as the central weaknesses in Freud's attitude toward ethics, art, philosophy, and the practice of psychotherapy. PMID- 8344775 TI - Clinical application of a dysregulation model of illness and disease: a case of spasmodic torticollis. AB - A case of spasmodic torticollis is described to demonstrate the clinical usefulness of a new theoretical model of somatic illness and disease. Based on a conception of the living organism as a self-regulating system, the model attributes somatic disorders to a variety of regulatory disturbances including deficits in affect regulation and in the ability to maintain a stable and cohesive self. Throughout the analytical treatment, attention was given to repairing deficits in the patient's self-organisation, and to elevating chaotic impulses and inchoate emotions from a primitive sensorimotor level of experience to a mature representational level where they could be valued for their signal function and modulated through imaginal activity and communication with others. Analysis of the patient's pathologic internal object relations modified his self organisation, and enabled him to establish regulatory interpersonal relationships that complemented his enhanced self-regulatory capacities. These changes were accompanied by a gradual resolution of the patient's torticollis. PMID- 8344776 TI - Tiresias and the breast: thinking of Lacan, interpretation, and caring. AB - Lacan's intellectual complexity and fascination with language are too often taken as an indication that in his conception of analysis there is no room for caring and love. In this paper we argue that this impression represents a misunderstanding of Lacan. We explore the role of the analyst according to Lacan, both as the 'subject of absolute knowledge', 'supporting the function Tiresias' and the 'man of care' with breasts. To Lacan, the process of analysis is an adventure into the realm of the exotic where there is a complexity of excitement and deep anxiety, an interplay of words and illusive exploding breasts, the birth and death of desire, and the confrontation with the illusion of 'self'. The analyst recognises the patience and courage necessary to face this and to understand that 'life is a foreign language; all men mispronounce it' (Morley, 1925, p. 188). PMID- 8344777 TI - What sort of a thing is a religion? A view from object-relations theory. AB - This paper suggests that a religion is not, as Freud proposed, a science-like thing, refutable by evidence. It is a socially constructed and maintained system of internal objects, analogous to those spoken of in psychoanalysis. Like analytic internal objects, religious objects have a heuristic function but no material existence. Unlike analytic objects, they are derived from a definite cultural tradition and are elaborated over time to meet the experience of practitioners. They may be understood to have a function of 'containing' the feelings, thoughts and fantasies arising in individual practitioners, and of making these experiences comprehensible. These objects then enable the believer to speak more truthfully of, and relate more fully to, the larger matrix within which the human world is situated. Finally, the suggestion is made that, as with analytic internal objects, religious objects may best be judged by their long term effects on the lives of believers. PMID- 8344779 TI - [The evolution of mortality in the first year of life in Spain (1975-1988)]. AB - In recent years, the rate of decline in infant mortality and the proportional mortality by some causes of death in the first year of life have had important changes. The objectives of this study are to describe such changes, and to suggest hypotheses about their meaning. Infant, early neonatal, late neonatal and postneonatal mortality rates from 1975 to 1988 were calculated with information from the death register. Also, several indicators of the trends of those rates and proportional mortality by "certain conditions originating in the perinatal period" have been calculated. The reduction in infant mortality was due, mainly, to early neonatal mortality, which had an annual average decline of 4.6% during the study period. The proportional mortality and the mortality rate by perinatal conditions in the postneonatal period increased between 1975 and 1988. The first increased from 1.3% to 5.2%, and the second from 0.07 to 0.15 per 1000 live births. Hypotheses about the meaning of these results are suggested, and some actions are proposed in order to monitor and conduct research on mortality during the first year of life. PMID- 8344778 TI - [The prediction of the minimum incidence of AIDS in Spain for the period 1992 1995]. AB - In order to estimate minimum AIDS incidence in Spain between 1992 and 1995, annual AIDS incidence up to 1991 has been obtained from the June 1992 update of the National Register. Correction was made for reporting delays in cases diagnosed since July 1989, in order to run a subsequent back calculation on all cases and for each separate mode of transmission. It was assumed that no new HIV infections would appear after 1991. Since 1981 to 1995, more than 38,000 AIDS cases will have been diagnosed. Minimum AIDS incidence as forecast exhibits a rise between 1992 and 1995 for the total number of cases and for all categories of transmission, except for recipients of blood and blood products, and children of mothers at risk. Real incidence will probably prove higher than estimated owing to the effect of new infections which may arise, and to the underreporting of cases. PMID- 8344780 TI - [The follow-up and monitoring of forecasts: the case of asthma epidemics in Barcelona]. AB - In this work we discuss several procedures of evaluation of time series models and analyze practical aspects of the management of a data base relative to a health information system devoted to the epidemiological surveillance and the detection of unusual values that could correspond to epidemic events. The analyzed statistical information corresponds to the time series of the number of emergency room admissions for asthma in several hospitals of Barcelona city, between the first of January of 1985 and the seventh of september of 1987. Among the three analyzed methods, the one based on the correlations of the one-step ahead residuals (the second one) is the most specific and, furthermore, it doesn't require the previous definition of an epidemic day. In addition, this second procedure has less analytical and computational difficulty. PMID- 8344781 TI - [Lateness in the treatment of diabetic retinopathy: the efficacy of an effective treatment]. AB - Despite the efficacy of laser photocoagulation as the treatment for diabetic retinopathy, this condition is the leading cause of blindness in developed countries. In this survey we have tried to find out whether this lack of effectiveness is due to a lack of adequate control and screening. As a proxy measure for this we have developed an indicator called "lateness" and we have followed a sample of diabetics drawn from the two public hospitals in Vizcaya (Spain). Seventy five percent of them were not at regular intervals and half of the sample was late for treatment. Among these, Insulin-dependent diabetics of older age and with more years of the disease are at a higher of entering late for treatment. We could not find any risk factor lateness among non insulin dependent diabetics. We concluded that most of diabetics are not adequately followed up for the prevention of diabetic retinopathy, and when they are referred to treatment it is too take the most advantage of it. PMID- 8344782 TI - [Hospital financing systems: an analysis of trends and a study of the consistency of reform proposals for introduction into public health systems]. AB - The author comments in this paper on the recent literature on reforms in hospital reimbursement systems. Instead of taking a theoretical approach to this topic, the article adopts a "middle of the road" view, by looking at the consistency of applying some of these reforms (mainly on contract management and DRGs) in Public Health Systems. After recognising some of the existing problems in the management of public hospitals in Spain, the author advocates for a common sense strategy to health reforms in terms of the following: (i) at the time of implementing changes in the hospital sector keep targets defined as simple as possible, (ii) go to reforms through a step-by-step procedure, and (iii) whenever things look complex, use basic "house-keeping" economics, instead of just importing additional economic literature from abroad. PMID- 8344783 TI - [The 1991 population census: the principal new changes]. PMID- 8344784 TI - Fluorometric assessment of equivalent healthy lens age for people with diabetes. PMID- 8344785 TI - Detection of melanocytes from uveal melanoma in peripheral blood using the polymerase chain reaction. AB - PURPOSE: Uveal melanoma is the most common intraocular malignancy in adults and can cause loss of vision in the affected eye and death from metastasis, usually to the liver. The techniques currently used to detect cellular dissemination from the tumor are inadequate, and lack the sensitivity required for the detection of low levels of melanocytes in the peripheral blood of patients. The detection of circulating melanocytes is important as an early indication of the possibility of metastasis. METHODS: The viability of reverse transcription/polymerase chain reaction amplification of the tyrosinase gene to detect circulating melanocytes was examined as a first sign of dissemination from uveal melanoma. RESULTS: It was shown that it is possible to detect as few as ten circulating melanocytes in 5 ml of blood. Blood-borne dissemination was also detected in three of six patients with uveal melanoma examined. Two of these patients had clinically confirmed widespread metastases. A positive result was also recorded in one patient in whom there was no other evidence for tumor dissemination. Overt metastatic disease developed in this patient 9 months after blood collection. CONCLUSIONS: The success of this technique has important implications for the detection of circulating tumor cells from uveal melanoma, as an early indication of dissemination. This may be important when considering the administration of adjuvant therapy. PMID- 8344786 TI - Visual pigment gene changes in adrenoleukodystrophy. AB - PURPOSE: The gene for X-linked adrenoleukodystrophy, a neurodegenerative disorder, is closely linked to the red/green color pigment genes on the distal X chromosome Xq28 and one kindred is known to have a genetic change affecting both loci. The purpose of this article is to perform a systematic assessment of the frequency of this situation in many affected kindreds. METHODS: Recombinant DNA probes were used in blot hybridization studies to determine the structure of the color pigment genes in affected males from 59 different adrenoleukodystrophy kindreds. Whenever possible, color vision was measured using the Farnsworth 100 Hue test. RESULTS: Eleven of the 59 kindreds had abnormal color pigment gene clusters; these included fusion genes and changes in gene number. Only one kindred had a deletion of sequences immediately 5' to the color pigment genes. CONCLUSIONS: The incidence of color pigment gene changes in our 59 adrenoleukodystrophy kindreds is approximately twice the frequency of defective color vision reported in historic studies but is about the same as that found in studies of the actual genes in large populations. However, the range of changes in the color pigment genes in adrenoleukodystrophy is broader than encountered in most populations. Changes in the highly conserved color pigment genes reflect reorganizations in the Xq28 chromosomal region, some of which involve the contiguous gene for adrenoleukodystrophy. PMID- 8344787 TI - Sites of cone system sensitivity loss in retinitis pigmentosa. AB - PURPOSE: To examine the sites of cone sensitivity loss in patients with retinitis pigmentosa by comparing focal electroretinographic and psychophysical modulation thresholds. METHODS: Both psychophysical and electrophysiologic increment threshold curves were obtained in retinitis pigmentosa patients and a group of age-matched, normally-sighted adults. RESULTS: The majority of the retinitis pigmentosa data could be accounted for by a vertical displacement of the normal curve. The retinitis pigmentosa patients showed similar patterns of cone sensitivity losses using both techniques. CONCLUSIONS: The combined electrophysiologic and psychophysical results provide support for an outer retina locus for these cone sensitivity losses. The data suggest that these deficits may be caused by a spatially independent loss of cone photoreceptors with normal adaptation properties in the remaining photoreceptors. PMID- 8344788 TI - Effect of vitamin A deficiency on the adhesion of rat corneal epithelium and the basement membrane complex. AB - PURPOSE: To understand the underlying mechanisms responsible for the easy removal and sloughing of corneal epithelium in vitamin A deficiency. METHODS: An animal model of vitamin A deficiency, the vitamin A-deficient rat (A-rat), transmission electron microscopy, computer-assisted morphometric analysis and indirect immunofluorescence were used to study the adhesion of rat corneal epithelium to its basement membrane with emphasis on structure and molecular composition of the anchoring structures such as the hemidesmosome and bullous pemphigoid antigen. RESULTS: Transmission electron microscopy resolved numerous microseparations of the basal epithelial cell membrane from the basement membrane with intervening segmental basement membrane duplications and electron dense deposits. Morphometric analysis disclosed a statistically significant reduction in the frequency and size of hemidesmosomes. Four weeks after supplementing the diet with retinyl acetate (700 micrograms/week), significant reversal of these same structural abnormalities could be detected. Immunofluorescence staining for bullous pemphigoid antigen, a component of the adhesion complex, showed intense staining of the basal epithelial cytoplasm but weak and discontinuous staining of the basement membrane. Weak staining for laminin was also evident in A- corneas. In contrast, normal corneas displayed no cytoplasmic staining for bullous pemphigoid antigen and intense staining of the basement membrane for bullous pemphigoid antigen and laminin. CONCLUSIONS: The authors propose that structural abnormalities of the epithelial basement membrane complex are responsible for the observed loose epithelial adhesion and sloughing, as well as other known abnormalities of healing in the vitamin A-deficient rat cornea. PMID- 8344789 TI - Ontogeny of corneal epithelial tight junctions: stratal locale of biosynthetic activities. AB - PURPOSE: On reaching the surface position, corneal epithelial cells assemble a tight paracellular barrier rapidly. The purpose of this study was to identify at what maturation stage the cells acquire biochemical elements underpinning this ability. METHODS: Rabbit corneas were subjected to a digitonin-exposure protocol that results in the devitalization and desquamation of the three outermost cell layers of the 5-6-layer thick epithelium and thus, exposes winglike cells to the tear surface. Corneas were then mounted in Ussing-type chambers to measure transepithelial resistance and solute fluxes. RESULTS: After the devitalization treatment transepithelial resistance remained near baseline for 2 hours and then rose to 8.24 +/- 3.12 K omega.cm2 (+/- SD, n = 15) during the next 8 hours. This increase was matched by increases in the resistance to the paracellular flow of mannitol. Transmission electron microscopy confirmed de novo formation of tight junctions over this time span in the new surface. The addition of transcription (actinomycin D; alpha-amanitin), translation (cycloheximide), core glycosylation (tunicamycin), and endoplasmic reticulum-to-Golgi traffic (brefeldin A) inhibitors immediately after the devitalization protocol prevented the transepithelial resistance raise. Introducing time delays between the cell devitalization and the addition of these biosynthesis inhibitors reduced their effect; a time delay of 90 minutes abolished the inhibition by alpha-amanitin. CONCLUSION: Devitalization of overlying cells induces the assembly of a tight paracellular barrier in the wing cells. The process requires and includes the synthesis of essential transcripts and proteins that were initially absent in these cells. In vivo, the synthesis of these elements must occur as cells reach the squamous stage of maturation. PMID- 8344790 TI - In vitro propagation of human ocular surface epithelial cells for transplantation. AB - PURPOSE: To examine the possibility that ocular surface epithelial cells might be grown in culture for use as grafts. METHODS: The proliferative capacity of epithelial cells cultured from the conjunctiva, limbus, and central cornea of normal human eyes was compared. Single cells disaggregated from approximately 1 mm2 biopsy specimens were serially cocultured with lethally irradiated mouse 3T3 fibroblasts. To study the cells' ability to reform a stratified epithelium, confluent limbal cultures were released as an intact cell sheet with the enzyme Dispase and transplanted to a dermal connective tissue bed in nude mice. Attachment and differentiation properties of the reconstituted epithelium were examined immunohistochemically. RESULTS: Central corneal epithelial cells could not be propagated; they senesced in first or second passage. In contrast, limbal epithelial cells exhibited a substantial (i.e., mean of 23 population doublings) and conjunctival cells a moderate (i.e., mean of 11 population doublings) proliferative capacity. Within 4 days of transplantation to the nude mouse dermis, cultured limbal epithelial cells formed an epithelium 5-6 cell layers thick. The epithelium adhered firmly to the graft bed, and deposition of the basement membrane and anchoring fibril protein collagens IV and VII and laminin was detectable immunohistochemically. The transplanted epithelium displayed limbuslike compartmental expression of keratins K3, K13, and K19, and of the enzyme enolase. CONCLUSIONS: These results support the concept that corneal epithelial stem cells are located in the limbus and indicate that cultured autologous limbal cells may function as grafts to permanently restore the corneal epithelium after severe ocular surface injury. PMID- 8344792 TI - Effect of Pseudomonas aeruginosa elastase, alkaline protease, and exotoxin A on corneal proteinases and proteins. AB - PURPOSE: To determine the effects of exoproducts from the corneal pathogen Pseudomonas aeruginosa on corneal proteinases and proteins. METHODS: Whole rabbit corneas were cultured in the presence or absence of broths conditioned with Pseudomonas aeruginosa, elastase, alkaline protease, and exotoxin A. Protein synthesis was assayed by adding 35S-methionine during the last 6 hours of culture. Caseinolytic assays and zymography on sodium dodecyl sulfate polyacrylamide gels containing casein and gelatin were used in the presence and absence of inhibitors to quantify and identify corneal proteinases. RESULTS: The major proteinases released by the corneas were 92/89 kD (MMP9) and 65 kD (72 kD gelatinase, MMP2) gelatinases and a 97 kD caseinase. Minor proteinases observed included 184, 166, 156, 153, 126, 111, 102, 60, 57, and 43 kD gelatinases and 170, 136, 85, and 54 kD caseinases. P. aeruginosa elastase at 1 microgram/ml cleaved the 92 kD gelatinase to yield a 77 kD active form and cleaved the 65 kD gelatinase to yield a 57 kD active form. At 25 micrograms/ml elastase, the gelatinases were degraded. P. aeruginosa alkaline protease had no effect on the 92 or 65 kD gelatinases. Both elastase and alkaline protease degraded the 97 kD caseinase. Proteinases other than elastase and alkaline protease in P. aeruginosa103- and P. aeruginosa01-conditioned broths also activated and/or degraded corneal proteinases. Exotoxin A inhibited the synthesis of the 92 kD gelatinase and most other proteins. The 72 kD gelatinase and the 97 kD caseinase were released in the presence of exotoxin A. CONCLUSIONS: Pseudomonas aeruginosa exoproducts can contribute directly to keratitis caused by Pseudomonas organisms through toxic effects on corneal cells and degradation of corneal proteins and indirectly through the activation of corneal proteinases. PMID- 8344791 TI - Identification of integrins in cultured corneal fibroblasts and in isolated keratocytes. AB - PURPOSE: The integrins are a family of transmembrane glycoproteins that function in attachment of cells to one another and to the extracellular matrix. When cell- cell and cell--matrix interactions are altered, the population of integrins may change. In particular, removing cells from their normal environment may be used as a model of wounding. The current study reports the identification of the integrins expressed at the cell surface of noncultured keratocytes and of cultured corneal fibroblasts, which are derived from keratocytes grown in primary culture. METHODS: For integrin identification, the surface proteins of keratocytes and cultured corneal fibroblasts were labeled with biotin, and the integrins were immunoprecipitated using anti-integrin antibodies. Attachment assays determined (1) the extracellular matrix preference of the cultured corneal fibroblasts and (2) the effects of function-perturbing antibodies against the fibronectin receptor (alpha 5 beta 1) or against other beta 1-containing integrins. RESULTS: The integrins of noncultured keratocytes were present as heterodimeric alpha, beta surface proteins that were immunoprecipitated by anti beta 1, anti-alpha v, anti-alpha 6, anti-alpha 3, anti-alpha 1, and anti-beta 3. Furthermore, when the keratocytes were placed in culture, the integrin pattern changed. The classic fibronectin receptor, alpha 5 beta 1, is then expressed along with additional integrins that bind to fibronectin. Using attachment assays, we determined that the cultured corneal fibroblasts prefer fibronectin to collagen, vitronectin, or laminin as extracellular matrix substrate. In addition, function-perturbing antibodies against the fibronectin receptor (alpha 5 beta 1) or against beta 1 inhibit attachment of cultured corneal fibroblasts to fibronectin. CONCLUSIONS: Receptors for fibronectin and other extracellular matrix molecules are expressed at the cell surface in cultured corneal fibroblasts, and are in position to play a significant functional role as seen in attachment to extracellular matrix. PMID- 8344794 TI - Extraction of choriocapillaris hemodynamic data from ICG fluorescence angiograms. AB - PURPOSE: There are conflicting views about the organization of the posterior pole choriocapillaris, particularly concerning blood flow through it, and there are difficulties associated with attempting to obtain such information using histologic techniques, sodium fluorescein angiography, or both. The present study uses a method of analysis based on high-speed angiograms to investigate posterior pole choroidal blood flow. METHOD: The analysis method employed is based on the premises that dye filling of the choriocapillaris is more rapid (because it is pulsatile) than dye filling of the underlying larger diameter vessels, and that fluorescence from these two overlapping layers is additive. The described analysis algorithm was applied to high-speed ICG fluorescence angiograms to emphasize information about choriocapillaris hemodynamics. RESULTS: The analysis method was demonstrated in rhesus monkeys, and results indicate that the posterior pole choriocapillaris does not behave as a homogeneous structure, consisting of discrete lobular segments. In general, the cycle of dye filling of the choriocapillaris begins in the macular area and progresses radially toward the periphery in a wavelike manner, the filling cycle beginning with and being completed during one cycle of the intraocular pressure pulse. CONCLUSIONS: It is possible to extract information related to choriocapillaris blood flow from high speed ICG angiograms when a fairly well-defined dye bolus wavefront is present. Interpretation of the results suggests that the choriocapillaris lobules fill in a pulsatile manner, out of phase with each other, and may act thereby to dissipate the blood volume entering the choroid during each cardiac cycle in such a way that the retinal macular is not significantly displaced by expansion of the choroidal vascular volume. Depending upon the distribution of pressure gradients across a group of lobules, blood may flow from one lobule into or even through an adjacent one. PMID- 8344793 TI - Adenosine-mediated autoregulation of retinal arteriolar tone in the piglet. AB - PURPOSE: To determine if the purine vasodilator adenosine participates in mediating autoregulatory dilations of the retinal microcirculation in vivo. METHODS: The retinal microcirculation of isoflurane-anesthetized newborn pigs was observed by videomicroscopy (x310). Systemic hypoxia (PaO2 = 24 +/- 1 mm Hg; n = 8) or hemorrhagic hypotension (MABP = 41 +/- 1 mm Hg; n = 5) was induced, and the effect of intravitreal microsuffusion of 0.4 nmol of the adenosine receptor antagonist 8-sulfophenyltheophylline (8SPT) on retinal arteriolar dilations resulting from these stimuli were measured. The effect of potentiation of endogenous interstitial adenosine concentrations with 0.2 nmol 4-nitrobenzyl-6 thioinosine (NBTI) on the response to hypotension (MABP = 43 +/- 2 mm Hg; n = 4) was also determined. RESULTS: The significant vasodilatative response of the retinal arterioles to systemic hypoxia (36 +/- 8% increase in diameter above baseline; P = 0.0012) was attenuated 55% (P < 0.0001) by the adenosine antagonist 8SPT. Similarly, the significant arteriolar vasodilation induced by systemic hypotension (29 +/- 3% increase in diameter; P < 0.0001) was inhibited 76% by 8SPT (P = 0.0002). When adenosine reuptake was inhibited with NBTI, the arteriolar dilation induced by hypotension (32 +/- 5% increase in diameter; P = 0.0234) was potentiated 100% (P = 0.0117). CONCLUSIONS: Our finding that inhibition or potentiation of endogenous adenosine action uniquely affected retinal arteriolar dilatative responses to hypoxia and hypotension suggests that adenosine is a key participant in mediating autoregulatory adjustments in retinal blood flow in the eye of the newborn. PMID- 8344795 TI - Local anesthetic drugs reduce endothelium-dependent relaxations of porcine ciliary arteries. AB - PURPOSE: During retrobulbar anesthesia ocular hemodynamics are altered. The purpose of this study is to investigate the effects of local anesthetics in isolated porcine ciliary arteries (diameter between 200 and 400 microns). METHODS: Isolated porcine ciliary arteries were suspended in myograph systems filled with modified Krebs-Ringer solution for isometric tension recording. RESULTS: In quiescent or serotonin-precontracted arteries, lidocaine, bupivacaine, or mepivacaine (10(-9)-10(-5)M) evoked no change in vascular tone. However, all local anesthetics (10(-5)M) and bupivacaine (10(-5)-10(-6)M) reduced endothelium-dependent relaxations to bradykinin (10(-9)-10(-6)M), whereas the endothelium-independent relaxations to the nitric oxide-donor 3-morpholino sydnonimine (SIN-1; 10(-9)-10(-5)M) were unaffected by local anesthetics. The addition of L-arginine (10(-4)M) markedly reduced the inhibitory effects of bupivacaine on endothelial vasodilatation function. CONCLUSION: These findings demonstrate that in porcine ciliary arteries, local anesthetics impair endothelial formation of nitric oxide from L-arginine after stimulation with bradykinin, which may contribute importantly to the reduction in blood flow to the eye during retrobulbar anesthesia. PMID- 8344797 TI - Does topical hydrogen peroxide penetrate the cornea? AB - PURPOSE: To determine under what conditions hydrogen peroxide (H2O2) can penetrate the cornea and cause increased concentrations of H2O2 in the aqueous humor. METHODS: Rabbit corneas were exposed in vitro and in vivo to H2O2 concentrations up to 60 mmol/l either in a 600 microliter volume or as consecutive drops. H2O2 was measured over time either in the endothelial superfusate or in tapped samples of aqueous humor, and in the fluid applied to the ocular surface. The stability of exogenous H2O2 added directly to aqueous humor was also determined. RESULTS: Exogenous H2O2 in aqueous humor decays with a half-life of 20 minutes, chiefly as a result of catalase activity. When applied to the entire ocular surface, 600 microliters of 60 mmol/l H2O2 caused no change in the concentration in aqueous humor, but when applied to the corneal surface alone, penetration occurred at 18 mmol/l and above. When applied as eight 40 microliters drops to the ocular surface the threshold for H2O2 penetration was above 36 mmol/l. CONCLUSIONS: H2O2 is rapidly eliminated on the ocular surface, chiefly by enzyme activity of the conjunctiva and cornea. Threshold for penetration of H2O2 into the aqueous humor depends on volume, concentration, duration, and ocular surface exposed. In a healthy eye, exogenously derived H2O2 is eliminated by enzyme activity of the aqueous humor and tissues surrounding the anterior chamber. PMID- 8344796 TI - Sustained delivery of retinoic acid from microspheres of biodegradable polymer in PVR. AB - PURPOSE: The aims were to obtain a controlled intravitreous release of retinoic acid (RA) by injecting drug loaded microspheres of biodegradable polymers and to study the potential use of this RA delivery system in a rabbit model of proliferative vitreoretinopathy (PVR). METHODS: The release of RA in vitro from 15 mg of 50-50 poly(DL-lactide-co-glycolide) (PLGA) in 1 ml of water at room temperature was measured with a spectrophotometer. In a rabbit model of PVR, 11 eyes were injected with 5 mg of microspheres containing 22 micrograms of RA/mg of PLGA, and seven control eyes were injected with microspheres of the same polymer that did not contain RA. In a third group, six rabbits were injected with 5 mg (n = 3) and 10 mg (n = 3) of microspheres containing RA. RESULTS: The initial concentration of RA was 20.8 micrograms/mg of PLGA. The release curve showed a fairly constant daily release of 7 micrograms/d for about 30 days. At 40 days, the release rate decreased to about 6 micrograms/d. After 40 days, 82.8% of the RA was released. Four of 11 treated rabbits (36%) and 7/7 (100%) controls showed tractional retinal detachment (TRD) (P < 0.01) after 2 months. Histopathologically, a mild, localized, foreign body reaction was observed. CONCLUSIONS: The authors obtained a sustained release of RA from PLGA microspheres in vitro for 40 days. A single injection of RA-loaded microspheres in suspension in BSS was effective in reducing the incidence of TRD after 2 months in a rabbit model of PVR. PMID- 8344798 TI - Expression of three forms of melanoma growth stimulating activity (MGSA)/gro in human retinal pigment epithelial cells. AB - PURPOSE: To characterize mRNA expression and protein production of the cytokine MGSA/gro in human retinal pigment epithelial (RPE) cells and to determine whether expression of MGSA/gro is modulated by serum and the cytokines interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), or transforming growth factor beta (TGF beta) mediators implicated in proliferative vitreoretinopathy (PVR). METHODS: Reverse-transcription polymerase chain reaction was used to determine the steady-state mRNA expression of three forms of MGSA/gro, alpha, beta, and gamma, by cultured human RPE cells in the presence or absence of recombinant IL-1 beta, TNF alpha, or TGF beta, or when serum-starved cells were re-fed with medium containing serum. Immunocytochemistry was used to characterize RPE cell-associated MGSA/gro protein, and immunoprecipitation of MGSA/gro from cell-conditioned medium was used to demonstrate MGSA/gro secretion. RESULTS: MGSA/gro mRNA was expressed minimally under basal conditions. Expression for all three forms of MGSA/gro mRNA was induced in a dose- and time-dependent manner after exposure to IL-1 beta, to a lesser extent after exposure to TNF alpha, but not after exposure to TGF beta. Serum induced MGSA/gro alpha and gamma transcripts, but not beta transcripts. Cell-associated MGSA/gro was identified on RPE cells grown in the absence of cytokines, but MGSA/gro was not secreted under these conditions. Exposure to IL-1 beta did not consistently cause increased cell associated MGSA/gro; however, IL-1 beta induced secretion of MGSA/gro in a time dependent manner. CONCLUSION: MGSA/gro is produced by human RPE in response to mediators implicated in PVR. Because MGSA/gro is a pleiotropic modulator of cell proliferation and inflammation, it may contribute to the intraocular wound healing response that characterizes PVR. PMID- 8344799 TI - Combination drug testing of Mycobacterium chelonae. AB - PURPOSE: Medical therapy of Mycobacterium chelonae keratitis is difficult because there are so few effective antimicrobial agents and single agent therapy frequently fails clinically. To identify more effective medical treatment regimens, the in vitro antimicrobial efficacy of amikacin, the most frequently used single agent, was investigated in combination with four antibiotics previously reported to have activity against M. chelonae: erythromycin, imipenem, ciprofloxacin, and vancomycin. METHODS: The drug combinations were tested by the checkerboard method against seven corneal isolates of M. chelonae. RESULTS: The combination of amikacin with erythromycin or vancomycin consistently led to synergistic or additive effect, however the minimum inhibitory concentrations for vancomycin were very high. The combination of amikacin with imipenem or ciprofloxacin led to results ranging from antagonism to additive effects. CONCLUSIONS: Of the antibiotics tested, erythromycin showed the most activity against M. chelonae in combination with amikacin. In vitro combination drug testing of M. chelonae by the checkerboard method should be further evaluated for clinical relevance in microbial keratitis. PMID- 8344800 TI - Prejunctional modulation of norepinephrine release in the human iris-ciliary body. AB - PURPOSE: To characterize the prejunctional mechanisms that control the impulse evoked release of norepinephrine in the isolated, superfused human iris-ciliary body. METHODS: Human iris-ciliary body tissue segments were preincubated with 3H norepinephrine, superfused and electrically-stimulated in vitro to evoke the discharge of 3H-norepinephrine. The effects of prejunctional modulators on evoked 3H-norepinephrine overflow were evaluated. RESULTS: Stimulation-evoked (but not spontaneous) 3H-norepinephrine release was inhibited by alpha 2-adrenergic, muscarinic, dopaminergic, neuropeptide Y, and prostaglandin agonists and was enhanced by angiotensin II. Agonist-induced effects on 3H-norepinephrine overflow were blocked by selective antagonists, where available. Yohimbine and atropine alone enhanced 3H-norepinephrine output, suggesting that prejunctional alpha 2 adrenergic and muscarinic receptors undergo tonic activation by endogenously released neurotransmitters. CONCLUSIONS: Human ocular sympathetic nerves express inhibitory alpha 2-adrenergic, muscarinic, dopaminergic, prostaglandin, and neuropeptide Y receptors and facilitatory angiotensin II receptors that control the impulse-evoked release of 3H-norepinephrine. These receptors may be useful targets for pharmacologic manipulation of the adrenergic system in vivo. PMID- 8344801 TI - Myopia and myopic progression among schoolchildren: a three-year follow-up study. AB - PURPOSE: To discuss the factors that might explain the rate of myopic progression and the degree of myopia after a 3-year follow-up among schoolchildren with myopia. METHODS: Myopic progression among 238 schoolchildren was followed up in a randomized clinical trial of myopia treatment. The associations between the explanatory factors and myopic progression and the final value of the spherical equivalent after the follow-up were studied by analysis of variance and regression analysis. RESULTS: Myopia progressed faster among girls than boys. According to the regression models for the boys, 25% of the variation of myopic progression and 57% of the final spherical equivalent could be explained by initial spherical equivalent, age at receiving first spectacles, time spent on sports and outdoor activities, and on reading and close work. Among the girls, 30% of myopic progression could be explained by age at receiving first spectacles, time spent on reading and close work, and reading distance. Similarly, 49% of the final spherical equivalent could be explained by age at receiving first spectacles, initial spherical equivalent, time spent on reading and close work, and reading distance. The rest of the variations could not be explained by the variables measured in this study. CONCLUSIONS: The factors with the most significant relationships to myopic progression were sex, age of onset, and degree of myopia at the beginning of the follow-up. Myopic progression and final myopia were related to time spent on reading and close work and to reading distance but not, however, to accommodation stimulus. PMID- 8344802 TI - Actin filament organization during endothelial wound healing in the rabbit cornea: comparison between transcorneal freeze and mechanical scrape injuries. AB - PURPOSE: To compare and contrast the in vivo mechanism of wound healing after mechanical scrape and transcorneal freeze (TCF) injury in a rabbit eye model by examining changes in the cytoskeletal organization of contractile, filamentous actin (f-actin) microfilaments as relates to differences in cell migration or translocation during endothelial repair. METHODS: Endothelial wound healing after mechanical scrape and transcorneal freeze injury was studied in rabbit eyes using laser scanning confocal microscopy (LSCM). Central corneal mechanical scrape injury was made using an olive tip cannula, and TCF injury was made using a 3-mm diameter stainless steel probe cooled with liquid nitrogen. Cytoskeletal changes in f-actin stained with phalloidin-FITC were observed during wound healing using LSCM. RESULTS: At 6 hours after mechanical scrape, the leading edge of the migrating sheet showed a decrease in the intensity of phalloidin-FITC staining, suggesting a decrease in cortical f-actin. Migrating endothelial cells in vivo did not appear to develop stress fibers after mechanical scrape, which is consistent with an in vitro cell spreading mechanism of endothelial wound healing. By 24 hours, the denuded area was almost fully resurfaced by migrating endothelial cells. On the other hand, TCF injury produced fibroblastic changes in the endothelial cells with extension and elongation of spindle-shaped endothelial cells at the leading edge by 24 hours after injury. Fibroblastic endothelial cells developed prominent actin stress-fibers, which is consistent with an in vitro cell migration mechanism of endothelial wound healing. Three days after TCF, the wounded area was resurfaced with two cell types: rough, fibroblast-like cells forming a retrocorneal fibrous membrane having prominent f-actin bundles or stress fibers with few cell-cell junctions, and smooth, polygonal-shaped endothelial cells having tight cell junctions with a cortical distribution of f actin. After 28 days the retrocorneal fibrous membrane was posteriorly covered with normal endothelium. CONCLUSIONS: These data support the hypothesis that endothelial wound healing involves two separate, injury-dependent, mechanisms- cell spreading and cell migration. PMID- 8344804 TI - Hyperlucent thorax from rotation. Anatomic basis. AB - RATIONALE AND OBJECTIVES: The authors studied a large group of patients with a computed tomography (CT)-based model to evaluate the presence, significance, and anatomic basis of unilateral hyperlucency from patient rotation. METHODS: Chest CT sections at three levels in 65 consecutive patients undergoing routine diagnostic studies were read into a microcomputer. Radiographic transmittance data were calculated across each CT section at different degrees of rotation as well as for lateral decentering. Data were analyzed for the pattern of density variation both individually as well as in stratified subgroups. RESULTS: The data showed a trend of increasing radiographic transmission on the side opposite that of the anterior obliquity. The resulting optical density difference was small and was not clinically significant. Lateral decentering produced smaller changes than rotation. The anterior breast/pectoral structures are the etiology for the phenomenon. Optical density differences of 0.1 result from a difference in tissue thickness of 4 mm. CONCLUSIONS: The changes in radiographic transmission with rotation are small and are overshadowed by soft tissue compression. Rotation alone will result in decreased radiographic transmission on the side of anterior obliquity; thus, the left side will be more lucent in an right anterior oblique projection. PMID- 8344803 TI - Developmental expression of bFGF in the bovine retina. AB - PURPOSE: To examine the expression of bFGF in the developing bovine retina. METHODS: Fetal bovine eyes at 90, 120, 150, and 180 days gestational age, as well as adult bovine eyes, were immunohistochemically stained for the presence of bFGF. Detailed characterization of the anti-bFGF antibodies by immunoblot and Western blot analysis against pure FGF gene family standards and crude extracts of bovine retina were also performed. RESULTS: Expression of bFGF occurs beginning at 150 days of gestation, a period when photoreceptor development and secondary capillary network development is in process. No bFGF expression was found at 90 days, but primary capillaries were already apparent at this stage of development. CONCLUSIONS: Expression of bFGF in the developing bovine retina may play a functional role in outer retinal development. PMID- 8344805 TI - The relationship of trabecular and cortical bone mineral density to spinal fractures. AB - RATIONALE AND OBJECTIVES: The relationships between trabecular, cortical, or integral bone mineral densities (BMD) to spontaneous vertebral fractures was investigated. METHODS: In 360 Japanese women, ranging from 20 to 83 years of age, vertebral trabecular and cortical BMD were measured using quantitative computed tomography (QCT). Among 46 oophorectomized women, BMD was measured using QCT and dual-energy x-ray absorptiometry (DXA). RESULTS: For patients in their sixth and seventh decades, those with fractures could be differentiated from those without fractures by measuring their trabecular BMD using QCT. Cortical BMD of women with fractures and trabecular BMD more than 80 mg/mL was significantly lower than that of women without fractures and trabecular BMD less than 70 mg/mL. CONCLUSIONS: Trabecular BMD can be a good predictor of spinal fracture. Cortical BMD may be important in cases with decreased trabecular BMD. PMID- 8344806 TI - Double contrast small bowel follow-through with an acid-resistant effervescent agent. AB - RATIONALE AND OBJECTIVES: A new technique was developed to achieve double contrast examinations in the small bowel without intubation. METHODS: Effervescent granules and tablets were coated with an acid-resistant acrylic lacquer to provide selective enteric gas release. The coating thickness was 15% of dry weight for the granules and 1 to 4.5 mg/cm2 for the tablets. Fifty patients were examined using the method in a controlled study. All examinations were reviewed by two radiologists using a three-step quality score. The results were compared to 20 enteroclysis examinations. RESULTS: Image quality was better for the coated tablets compared with the granules (P < .01). The double-contrast small bowel follow-through (DC-SBFT) provided a better quality examination in the terminal small bowel than in the jejunum. Enteroclysis yielded better results for the jejunum, but was not superior in the terminal ileum. Average time of fluoroscopy was 477 seconds for the DC-SBFT (n = 50) compared with 952 seconds for patients receiving enteroclysis (n = 528). No side effects or adverse reactions occurred due to contrast media application. CONCLUSIONS: The results of this new method are preliminary, yet promising. For young patients and certain indications it may provide a less invasive alternative to enteroclysis. PMID- 8344807 TI - Clot-blood contrast in fast gradient-echo magnetic resonance imaging. AB - RATIONALE AND OBJECTIVES: Contrast between clot and blood in magnetic resonance imaging (MRI) at 1.5T using fast gradient-echo pulse sequences (fast GRE), with 8 ms < TR < 20 mseconds was studied both in vitro and in clinical human deep venous thrombosis (DVT) to assess whether good contrast could be obtained at such short repetition times and at clinically relevant flow rates. METHODS: In vitro studies used an apparatus that contained flowing MnCl2[aq] (water adjusted with manganese chloride to have T1, T2 similar to blood) and an immobilized clot (T1, T2 similar to those in DVT) for flow velocities between 0 and 16.5 cm/sec. Seven patients with DVT were imaged with the fast GRE sequences to observe the clot-blood contrast in vivo. RESULTS: Peak contrast-to-noise ratio (CNR) was achieved using flip angles between 20 degrees and 40 degrees (increasing with flow velocity) with or without radiofrequency "spoiling," consistent with a natural spoiling effect of flow. The CNR between MnCI2[aq] and clot decreased less than 10% as TR was reduced 56% from 18 mseconds to 8 mseconds (30 degrees flip angle). In four patients with nonocclusive DVT, fast GRE imaging provided good contrast while in occlusive cases (three patients) the contrast was not as good as conventional GRE sequences with longer TR values (TR = 33 mseconds). CONCLUSION: A fast GRE sequence with TR = 8 mseconds, TE = 3 mseconds, and a flip angle = 40 degrees is a promising approach to speeding up the detection of nonocclusive clinical DVT. PMID- 8344808 TI - Absence of an angiogenic factor in large systemic arteriovenous malformations. AB - RATIONALE AND OBJECTIVES: Large symptomatic arteriovenous malformations (AVMs) are currently managed by a combination of surgery, embolization, and supportive measures. If patients with such lesions should have a circulating factor responsible for their growth and development, the evolution of a more rational therapy might be possible. METHODS: To explore this possibility, sera from 14 patients with high-flow systemic AVMs, widely distributed anatomically, were tested for the presence of a circulating growth factor using an assay already successfully used to isolate such a factor in diabetics with proliferative retinopathy. RESULTS: None of the patients tested positive for such a factor. CONCLUSIONS: This result, although negative, contributes to our knowledge of the biology of these uncommon but important lesions and leads us to conclude that, for the foreseeable future, embolization is likely to remain the most effective form of treatment for high-flow AVMs. PMID- 8344810 TI - In-vitro assessment of the behavior of magnetic resonance angiography in the presence of constrictions. AB - RATIONALE AND OBJECTIVES: Time-of-flight magnetic resonance angiography (TOF/MRA) is increasingly used to assess the nature and severity of stenotic blood vessels. Flow artifacts associated with high flows and/or narrow constrictions may confuse the interpretation of these studies. Accurate TOF/MRA evaluations demand an understanding of the nature of these flow effects. METHODS: A two-dimensional TOF pulse sequence was used to acquire images of five smoothly constricted phantoms at various flows. Analysis included assessment of phantom appearance and quantification of apparent constriction diameter and signal variations. RESULTS: Most notable flow phenomena were a cone-shaped region of high signal, a region of signal void, and signal preservation along the wall. When visible, constriction diameter was accurately measured. CONCLUSIONS: The behavior observed in TOF/MRA images can be understood by considering the contributing mechanisms of phase dispersion, turbulence, poststenotic flow eddies, flow reversal, and flow separation. PMID- 8344809 TI - Calculation of tissue attenuation with a clinical ultrasound unit. AB - RATIONALE AND OBJECTIVES: Five alternative methods for estimating tissue attenuation with a clinical ultrasound unit were evaluated. METHODS: Two homogeneous tissue mimicking phantoms (with known attenuations of 0.25 and 0.54 db/cm/MHz) and 22 human placentas were scanned. Attenuation coefficients were computed by linear regression of 1) L(f), the log spectral difference; 2) Fav (d), the average spectral frequency; 3) log[P(d)], the logarithm of the spectral power; 4) Fav (d) x log[P(d)]; and 5) (Fav(d) + log[P(d)])/2. RESULTS: Each of these five heuristics provided accurate estimates for the relative attenuations of the two phantoms. For placental tissue, method 3 provided better regression fits than methods 1 and 2. Methods 4 and 5 provide the best regression fits (P < .01). CONCLUSIONS: The combination of both frequency and power information in methods 4 and 5 compensates, in part, for nonlinearities introduced by tissue heterogeneity. A parameter that combines both frequency and time domain information is likely to provide more reliable estimates of attenuation than power or frequency measurements alone. PMID- 8344811 TI - Acute effects of shock waves on tumors assessed by magnetic resonance imaging. Possible role of blood flow reduction. AB - RATIONALE AND OBJECTIVES: The effects of shock waves on experimental tumors in vivo by gadolinium(+)-DTPA-enhanced magnetic resonance imaging (MRI) are assessed. METHODS: Two amelanotic hamster melanomas were implanted in the dorsal skin of 19 hamsters. In experiment 1 (n = 7), MRI of untreated tumors was performed before, and 5 and 15 minutes after intravenous injection of Gd(+)-DTPA. In experiment 2 (n = 12), 200 shock waves were applied on one of the implanted tumors. Magnetic resonance imaging was performed 15 minutes after treatment before, and 5 and 15 minutes after injection of Gd(+)-DTPA. RESULTS: In experiment 1, signal intensities (SI) of untreated tumors increased after injection of Gd(+)-DTPA. In experiment 2, enhancement was significantly delayed in shock-wave-treated tumors as compared with controls. Histology of the treated tumors revealed vascular damage. CONCLUSION: Differences in enhancement between shock-wave-treated and control tumors after injection of Gd(+)-DTPA are interpreted as the consequence of reduced and delayed accumulation of Gd(+)-DTPA in treated tumors due to shock wave induced vascular damage and reduced tumor perfusion. PMID- 8344812 TI - Effect of lidocaine on acute regional myocardial ischemia and reperfusion in the cat. An in-vivo 31P magnetic resonance spectroscopy study. AB - RATIONALE AND OBJECTIVES: The authors examined the relationship between myocardial infarction, high-energy phosphate compounds, and regional contractility after myocardial ischemia and reperfusion in cats. METHODS: Hemodynamic measurements, high-energy phosphate levels, and segmental shortening were measured every 30 minutes in two groups of cats subjected to 2 hours of occlusion of the left anterior descending coronary artery and 4 hours reperfusion. Group 1 (n = 10) animals were infused with a low level of lidocaine, 0.05 mg/kg/hr, while group 2 (n = 10) received a higher dose, 7.5 mg/kg/hr. The infarcted region was measured postmortem. RESULTS: Group 1 animals had larger infarcts (39 +/- 6 vs. 12 +/- 5% of jeopardy, P < .05) and less phosphocreatine recovery during reflow (52 +/- 7% vs. 73 +/- 2% of control, P < .01) than did group 2. Group 2 showed recovery of percentage systolic shortening during reflow (1.4 +/- 2% at 30 minutes vs. 7.1 +/- 2.3% at 4 hours, P < .05), whereas group 1 exhibited no improvement. A significant correlation was found between infarct size under the surface coil and phosphocreatine content during reflow, but not between contractile function and infarction size or metabolite levels during reflow. CONCLUSIONS: Lidocaine infusion enhanced recovery of myocardial contractility during reperfusion and decreased infarct size. Greater recovery of phosphocreatine during reperfusion was predictive of greater myocardial salvage during reperfusion. PMID- 8344813 TI - Hemodialysis and iopamidol clearance after subclavian venography. AB - RATIONALE AND OBJECTIVES: The dialyzability of iopamidol is unknown and was investigated in patients undergoing long-term hemodialysis for chronic renal failure. METHODS: Ten patients received 30 ml Niopam 300 (Bracco SpA, Milan, Italy) (identical to 18372 mg iopamidol) intravenously into a forearm vein to investigate for occult subclavian stenosis. RESULTS: The elimination half-life of iopamidol before hemodialysis was 69.6 hours and during 4 hours of hemodialysis was 3.5 hours. A single 4-hour hemodialysis cleared 55.7% (95% Ci 51-5-59.8) of the administered dose, while second and third dialyses cleared 25.3% (95% Ci 21.4 29.1) and 10.1% (95% Ci 7.7-12.6) of the administered dose, respectively. Two patients with significant residual urine excretion excreted more than 10% of the administered dose in the urine. For anuric patients, extrarenal clearance provided total body clearance of up to 0.266 L/hr. CONCLUSIONS: Hemodialysis is a rapid and efficient means of clearing iopamidol provided it is performed soon after the contrast study. PMID- 8344814 TI - Mechanism of gravity-dependent atelectasis. Analysis by nonradioactive xenon enhanced dynamic computed tomography. AB - RATIONALE AND OBJECTIVES: The physiologic mechanism of gravity-dependent atelectasis (GDA), a common finding identified during anesthesia, is not well understood. The purpose of this study was to determine whether an inherent reduction in alveolar volume or a reduction in alveolar ventilation is the more important causative factor for the development of GDA in an experimental animal model. METHODS: After uniform reduction of lung volume in ten rabbits by artificially induced pneumoperitoneum, dynamic inhalation computed tomography (CT) was performed using 50% nonradioactive xenon in oxygen. Time-CT attenuation value curves were fitted to an exponential function, CT value = a - b x e(-kt), and K value, which is proportional to the alveolar ventilation/alveolar volume ratio, was calculated by regression analysis. RESULTS: Gravity-dependent atelectasis occurred only in 5 of 10 rabbits. In this group, K values in the dorsal regions increased before the appearance of GDA. No significant change in K values in the ventral regions was observed. CONCLUSION: One mechanism of GDA may be a preferential reduction in alveolar volume without small airway collapse rather than alveolar volume loss secondary to decreased ventilation. PMID- 8344815 TI - How to implement a radiology quality improvement program. Pearls and pitfalls. AB - To get started and to help overcome some of the problems with implementation mentioned above, five essential things need attention: 1. Top level commitment; 2. Physician participation; 3. On-going education; 4. Performance measurement (both of the department and individual); 5. Up-front investment of time and resources. The fundamental changes in technology, financing, and accountability present formidable challenges to departments of radiology today. Fortunately, quality management techniques offer a way to meet the challenges and simultaneously improve efficiency of care and quality. Learning and practicing these techniques is not an easy task, but overcoming the obstacles to implementation and getting on with the job will prove very rewarding. PMID- 8344816 TI - The instructional effectiveness of a radiology multimedia textbook (HyperLung) versus a standard lecture. AB - RATIONALE AND OBJECTIVES: Information overload is a significant problem for the modern radiologist. This prospective study compares the instructional effectiveness of a multimedia textbook (HyperLung) with a lecture. HyperLung is a radiologic multimedia textbook about imaging diffuse lung disease created using a multimedia authoring tool, the Annotator (the University of Iowa Second Look Computing, Iowa City, IA), on the Apple Macintosh computer (Apple Computer, Cupertino, CA). METHODS: Forty-nine staff physicians and residents in the Department of Radiology were randomized to receive instruction either by HyperLung or by a lecture. The instructional content was the same in both groups, and both groups were tested before and after instruction. The actual time spent in each instructional situation was recorded. RESULTS: The instructional effectiveness of the multimedia textbook and lecture was equal. The instructional efficiency of HyperLung was only 60% of the lecture. Users of the multimedia textbook found it enjoyable and straightforward to use. CONCLUSIONS: Multimedia textbooks have a promising future in radiology education. PMID- 8344817 TI - The role of research in a radiotherapy training program. PMID- 8344818 TI - Uroradiology in Europe. PMID- 8344819 TI - Magnetic resonance imaging of angiographically occult run off vessels in peripheral arterial occlusive disease. PMID- 8344820 TI - Use of Medicare services before and after introduction of the prospective payment system. AB - OBJECTIVE: The case mix-adjusted pattern of use of health care services, especially posthospital care, is compared before and after the introduction of Medicare's Prospective Payment System (PPS). DATA SOURCES: The 1982 and 1984 National Long Term Care Surveys (NLTCS) linked to Medicare administrative records 1982-1986 provide health and health service use data for 12-month periods before and after the introduction of PPS. STUDY DESIGN: Case-mix differences between pre and post-periods are controlled by using the Grade of Membership model to identify health groups from the NLTCS data. Differences in timing (e.g., hospital length of stay) were controlled using life table models estimated for each health group, that is, service use patterns pre- and post-PPS are compared within groups. PRINCIPAL FINDINGS: Hospital LOS and admission rates declined post-PPS. Changes in the timing and location of death occurred but, overall, mortality did not increase. Changes in post-acute care service use by elderly, chronically disabled Medicare beneficiaries were observed: home health service use increased overall and among the unmarried disabled population. CONCLUSIONS: PPS did not adversely affect quality of care as reflected in mortality or in hospital readmissions. Moreover, the differential use of post-acute care, and changes in hospital LOS by health group, indicate that the system responded, specific to marital status and age, to the severity of needs of chronically disabled persons. PMID- 8344821 TI - Measuring differences and similarities in hospital caseloads: a conceptual and empirical analysis. AB - OBJECTIVE: This article conceptually and empirically evaluates alternative index measures that have been used to distinguish among hospital caseloads. It introduces two new measures. DATA SOURCES/STUDY SETTING: The study relies on 1987 Medpar data, which provide a 100 percent sample of Medicare Part A claims for the calendar year. STUDY DESIGN: Descriptive statistics indicate the sensitivity of alternative caseload measures to hospital bed size, region, and urban/rural location. Multiple regression analysis then examines the ability of the caseload measures to distinguish among hospitals based on hospital- and area-specific characteristics. DATA COLLECTION/EXTRACTION METHODS: A provider level file containing the number of cases treated by each provider in each DRG was constructed from the Medpar data and merged with data from the American Hospital Association and the Area Resource File. PRINCIPAL FINDINGS: Different indexes purporting to measure hospital specialization are often evaluating very different aspects of the hospitals' caseloads. Prior work has indicated a specialization among hospitals during the period from 1980 to 1985. Replication of this work using other indexes could verify the increase in specialization and might provide a clearer picture of market or hospital characteristics associated with changing caseloads. PMID- 8344822 TI - A variable-radius measure of local hospital market structure. AB - OBJECTIVE: To provide a radius measure of the structure of local hospital markets that varies with hospital characteristics and is available for all hospitals in the United States. DATA SOURCES: 1982 American Hospital Association (AHA) Survey of Hospitals, 1982 Area Resource File (ARF), and 1983 California Office of Statewide Health Planning and Development (OSHPD) discharge abstracts. STUDY DESIGN: The OSHPD data were used to measure the radii necessary to capture 75 percent and 90 percent of each hospital's admissions. These radii were used as the dependent variables in regression models in which the independent variables were from the AHA and ARF. To estimate predicted market radii, the estimated parameters from the California models were applied to all nonfederal, short-term, general hospitals in the continental United States. These radii were used to define each hospital's service area, and all other hospitals within the calculated radii were considered potential competitors. Using this definition, we calculated two measures of local market structure: the number of other hospitals within the radius and a Herfindahl-Hirschman Index based on the distribution of hospital bed shares in the market. DATA EXTRACTION METHODS: These measures were calculated for all nonfederal, short-term, acute care hospitals in the continental United States for whom complete data were available (N = 4,884). CONCLUSIONS: These measures are available from the authors on computer-readable diskette, matched to hospital identifiers. PMID- 8344824 TI - Hospital board effectiveness: relationships between governing board composition and hospital financial viability. AB - OBJECTIVE: Two theories--agency and managerialism--are compared with respect to their usefulness in explaining the role of insiders on the hospital board: whether their participation enhances or impairs board financial decision making. DATA SOURCES/STUDY SETTING: The study used 1985 hospital financial and governing board data for a representative sample of acute care California hospitals. STUDY DESIGN: Relationships were examined cross-sectionally between the presence or absence of insiders on the board and measures of hospital financial viability while controlling for the organizational factors of system affiliation, ownership, size, region, and corporate restructuring. PRINCIPAL FINDINGS: Multiple regression analysis found significant relationships between insider (CEO, medical staff) participation and hospital viability. CONCLUSIONS: These results support the managerial theory of governance by suggesting that the CEO and medical staff provide informational advantages to the hospital governing board. However, the cross-sectional design points to the need for future longitudinal studies in order to sequence these relationships between insider participation and improved hospital viability. PMID- 8344825 TI - Evaluation of HCFA's Medicare hospital mortality report. PMID- 8344826 TI - Back to bondage. PMID- 8344823 TI - Corporate and philanthropic models of hospital governance: a taxonomic evaluation. AB - OBJECTIVE: We assess the theoretical integrity and practical utility of the corporate-philanthropic governance typology frequently invoked in debates about the appropriate form of governance for nonprofit hospitals operating in increasingly competitive health care environments. DATA SOURCES: Data were obtained from a 1985 national mailed survey of nonprofit hospitals conducted by the American Hospital Association (AHA) and the Hospital Research and Educational Trust (HRET). STUDY DESIGN: A sample 1,577 nonprofit community hospitals were selected for study. Representativeness was assessed by comparing the sample with the population of non-profit community hospitals on the dimensions of bed size, ownership type, urban-rural location, multihospital system membership, and census region. DATA COLLECTION: Measurement of governance types was based on hospital governance attributes conforming to those cited in the literature as distinguishing corporate from philanthropic models and classified into six central dimensions of governance: (1) size, (2) committee structure and activity, (3) board member selection, (4) board composition, (5) CEO power and influence, and (6) bylaws and activities. PRINCIPAL FINDINGS: Cluster analysis and ANCOVA indicated that hospital board forms adhered only partially to corporate and philanthropic governance models. Further, board forms varied systematically by specific organizational and environmental conditions. Boards exhibiting more corporate governance forms were more likely to be large, privately owned, urban, and operating in competitive markets than were hospitals showing more philanthropic governance forms. CONCLUSIONS: Findings suggest that the corporate philanthropic governance distinction must be seen as an ideal rather than an actual depiction of hospital governance forms. Implications for health care governance are discussed. PMID- 8344827 TI - Health visitors torn between clients and employer. PMID- 8344828 TI - Staff to apply for 'own jobs' as GPs shift contract to save grades. PMID- 8344829 TI - Vistas of common sense in 233 words. PMID- 8344830 TI - Children behind bars. AB - Over half the women serving prison sentences are mothers--many with dependent children under 16. Three women's prisons have special mother and baby units but there is little provision for the majority of women prisoners to maintain contact with their children. Campaigners say too little thought is given to the rights of the children. PMID- 8344831 TI - Nicaragua. Deaths by a thousand cuts. Interview by Cath Jackson. PMID- 8344832 TI - Patch and practice: specialist roles for health visitors. AB - Health visiting is facing its biggest ever challenge from the government's decision to give GP fundholders the powers to purchase health visiting and other community nursing services, writes WALTER BARKER. Here he proposes that health visitors should specialise and work either as practice health visitors employed by GP fundholders or as community health visitors employed by FHSAs or public health directorates. This approach would retain a strong home support service for families in need while maintaining the health visitor's public health role, he argues. PMID- 8344833 TI - Health visiting and the new public health. PMID- 8344834 TI - How important are early mother/infant relationships? AB - Developmental psychologists tend to believe the early relationship between mother and baby has a major impact on the child's later cognitive, emotional and social development. Ruth Paradice argues that an infant's early relationship with its primary caretaker, though important, is but one in a rich social network and that babies may be more resilient than is generally believed. PMID- 8344836 TI - Some current issues for health visiting. AB - Michael Traynor argues that recent legislation with its emphasis not only on targeted, measurable and effective service but also on the importance of health promotion offers exciting opportunities for health visiting. But to take advantage of these, health visitors will need to become familiar with the growing body of research into the evaluation of health visitors' preventive, supportive and health promotion roles. PMID- 8344835 TI - Older patients are people first. AB - Older people, and their health, are widely seen as 'different', writes Paula Jones. Services for older people have failed to keep pace with the medical advances which have resulted in increased longevity; they are largely ignored in the 'Health of the nation' strategy. Here she questions society's attitudes to older people and examines the consequences for the delivery of health services and for older people themselves. PMID- 8344837 TI - Belfast. Working with girls. AB - Belfast has many of the social problems common in major British cities: soaring unemployment, teenage crime, joy-riding, high levels of teenage pregnancy, drug and alcohol abuse. In Belfast, these problems are further complicated by the political and religious divide which affects virtually every area of society. Maura Thompson reports on a unique health visitor-led initiative working with teenage girls. PMID- 8344838 TI - Measuring down: PRP pitfalls. AB - Within the next three years many NHS staff will be on a performance related pay (PRP) scheme, writes ROGER KLINE. PRP, together with job evaluation (see May Health visitor) is likely to become the main means of determining NHS staff pay. Already many senior NHS managers are on PRP and many trusts see it as one of their goals. PMID- 8344840 TI - Close contact theory and SIDS. PMID- 8344839 TI - Networking against harassment at work. PMID- 8344841 TI - Lessons from our children. AB - While the incidence of cancer is increasing among both children and adults, mortality rates have decreased for children, while they have increased for adults. Of children diagnosed with cancer today, 80% are predicted to be long term survivors. Although there are differences between children and adults with respect to the tumor types, biology, and outcome, there are common lessons which we can learn from our children regarding the genetics of cancer, its management and treatment, and the importance of longitudinal studies of the survivors. Specific pediatric cancers, such as retinoblastoma, have led to the recognition of tumor suppressor genes, now also observed among adult tumors including sarcomas, breast, lung, and bladder cancer. The presence of the tumor suppressor gene provides an understanding for the incidence of second malignant tumors among patients with heritable diseases. Furthermore, cancer prone families, such as those with the Li-Fraumeni syndrome, also carry the p 53 tumor suppressor gene; the presence of which greatly increases the risk of developing invasive cancer. Childhood cancer is rare; it represents only 1% of the total US cancer problem. However, 53% of all children with cancer, but only 2% of all adults, are studied via the NCI cooperative group mechanism. For some specific childhood tumors such as rhabdomyosarcoma and Wilms' tumor, as many as 70-85% of all cases are managed via NCI sponsored trials. Essentially all pediatric cancer is treated by interdigitating radiation with surgical resection and systemic chemotherapy. This approach has contributed to high cure rates. Finally, our understanding of the late effects of being a cancer survivor have come from longitudinal studies of children. The most severe long-term effects related to radiation in childhood pertain to growth and development, infertility, and second malignant tumor induction. Here the children treated for Hodgkin's disease have taught us the dose and volume effects on axial skeletal and soft tissue growth. Infertility issues are also treatment-related and may often be obviated by using gonadal shielding. The risk of secondary leukemia is related to dose and class of specific chemotherapeutic agents administered; it is 5.5% among children receiving 6 cycles of MOPP. There is a 22-fold risk at 30 years of age of solid tumor induction following radiotherapy for children with Hodgkin's disease. These serious concerns have been offset by current therapeutic approaches of using lower doses and smaller volumes of radiation with fewer cycles of less toxic chemotherapeutic agents. Childhood cancer ranks high among number of person-years of potential life saved annually.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8344842 TI - Pharyngeal wall carcinoma treated with radiotherapy: impact of treatment technique and fractionation. AB - PURPOSE: To determine whether a modification in treatment technique and the routine use of twice-daily fractionation have influenced the likelihood of local control in carcinomas of the hypopharyngeal and/or oropharyngeal wall. METHODS AND MATERIALS: Between October 1964 and July 1990, 99 patients with invasive, previously untreated T1-T4 squamous cell carcinoma of the pharyngeal wall were treated with continuous-course, external-beam radio-therapy with curative intent at the University of Florida. All patients had a minimum 2-year follow-up. RESULTS: The 2-year local control rates for patients treated with once-daily vs. twice-daily fractionation were T1, 100% each; T2, 67% vs. 92%; T3, 43% vs. 80%; and T4, 17% vs. 50%. The 2-year local control rates for patients treated with our former technique (posterior border placed at middle of the vertebral body when the portals were reduced off the spinal cord) vs. our current, modified technique (posterior border placed at posterior edge of the vertebral body) were T1, 100% each; T2, 57% vs. 100%; T3, 46% vs. 73%; and T4, 29% vs. 75%. The parameters of T stage, fractionation schedule, primary site, (oropharynx vs. hypopharynx) treatment technique, and lateral vs. posterior pharyngeal wall location were evaluated in a multivariate analysis for the end point of local control. T stage (p = .003), fractionation schedule (p = .001), and primary site (p = .028) were of independent prognostic significance. CONCLUSION: Twice-daily fractionation was the most important treatment-related variable in this patient population. PMID- 8344843 TI - The management of the clinically positive neck as part of a larynx preservation approach. AB - PURPOSE: For patients with squamous cell carcinoma of the head and neck with palpable neck node metastases, the standard management of the neck usually involves neck dissection and postoperative neck irradiation. A strategy of larynx preservation with induction chemotherapy and radiation therapy has been utilized for patients with locally advanced resectable cancer of the larynx, hypopharynx, and oropharynx. For patients treated in this non-surgical manner for the primary site, the optimal management of the clinically positive neck has not been clarified. To determine whether response to induction chemotherapy could help to select patients in whom neck dissection could be omitted in favor of definitive radiation therapy alone, we have analyzed our prospective larynx preservation experience. METHOD AND MATERIALS: Between 1983-1989, 80 patients were entered onto larynx preservation protocols involving 1-3 cycles of cisplatin based chemotherapy followed by radiation therapy with or without neck dissection. There were 54 patients with clinically positive necks to treatment, of whom 44% (24/54) had a complete response, and of whom 20% (11/54) had a partial response to chemotherapy in the neck. In 22 of these 35 patients with clinically positive necks who achieved a major neck response to chemotherapy, radiation therapy (median 66 Gy) was used as the only subsequent treatment of the neck. RESULTS: At a median follow-up of 25 months (range 7-83 months), neck control for this subset is 91% (20/22). Neck failure occurred in 20% (1/5) of patients with a partial response to chemotherapy treated without neck dissection and 6% (1/17) of node positive with a complete response. CONCLUSION: These results suggest that patients with clinically palpable cervical nodal metastases who have a complete response to chemotherapy and receive high dose radiation therapy have excellent neck control and may not need neck dissection. Further experience will be required to confirm these preliminary data and to determine if patients who achieve a partial response in the neck after induction chemotherapy can be treated with radiation therapy without neck dissection. PMID- 8344844 TI - Prognostic factors for local control and survival in T1 squamous cell carcinoma of the glottis. AB - PURPOSE: To evaluate the effect of host, tumor, and treatment-related variables on local control and survival in patients with T1N0M0 squamous cell carcinoma of the glottis. MATERIALS AND METHODS: Ninety-one patients with T1N0M0 squamous cell carcinoma of the glottic larynx were analyzed. Median follow-up was 9 years (range 2-25). Patients were treated with daily fractions of 180 cGy to 220 cGy to doses of 5925-7000 cGy (median 6400). The following factors were analyzed: age, sex, histologic grade, disease extent, beam energy, field size, total dose, dose per fraction, and elapsed treatment days. RESULTS: The 5-year actuarial local control was 80%. On univariate analysis, only elapsed treatment days and dose per fraction were significant factors for local control. Local control was 100% if treatment was completed within 42 days, 91% for 43-46 days, 74% for 47-50 days, 65% for 51-54 days, and 50% for 55-66 days (p = 0.0001). In patients treated at < 200 cGy per fraction, local control was 62% as compared to 87% for > or = 200 cGy per fraction (p = 0.006). On multivariate analysis, only elapsed treatment days was a significant factor for local control (p = 0.0001). The 5-year actuarial survival for the whole group was 92%. Elapsed treatment days was the only variable affecting survival. Survival was 100% if treatment was delivered within 42 days, 96% for 43-46 days, 94% for 47-50 days, 91% for 51-54 days, and 67% for 55-66 days (p = 0.02). The 5-year actuarial disease-specific survival was 95%, with treatment duration again being the only significant prognostic factor. Disease-specific survival was 97% for treatment completed within 39-54 days versus 80% for 55-66 days (p = 0.02). Only three (3.3%) patients experienced moderate or severe complications. None of the evaluated parameters impacted significantly on complications. CONCLUSION: We conclude that elapsed days is the most prognostically significant factor for local control and survival in patients treated with radiotherapy for T1 squamous cell carcinoma of the glottis. We recommend that these patients be treated with 210 cGy daily fractions to 6300 cGy. PMID- 8344845 TI - Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976-1985: survival after local recurrence. AB - PURPOSE: To study the value of re-irradiation, the overall survival and pattern of failures for patients with nasopharyngeal recurrence. METHODS AND MATERIALS: All the 891 patients with local recurrence following radiotherapy for nasopharyngeal carcinoma during 1976-1981 were retrospectively analyzed. Only 70% of them had local failure alone at the time of detection, and the T-stage distribution (by Ho's system) was 31% rT1, 16% rT2, 51% rT3, and 1% rT?. Seven hundred and six (79%) patients had been re-irradiated with various techniques and doses. Among those who failed, 50 had further irradiation. RESULTS: The overall 5 and 10-year actuarial cancer-specific survival rates were 14% and 9%, respectively. Patients with rT3 disease had the worst prognosis. Successful local salvage was achieved in 32% of those re-irradiated (26% of the whole series). The highest control rate was achieved by those treated with external radiotherapy to 60 Gy (equivalent) or above. Only 8/50 patients responded to the third course of radiotherapy. The cumulative incidence of late post-re-irradiation sequelae was 24%, and the treatment mortality rate 1.8%. Besides local failure, 54% had regional relapse and/or distant metastasis. Thus, only 16% of recurrent patients were totally disease-free at final assessment. CONCLUSION: The overall prognosis for patients with nasopharyngeal recurrence was grave. High dose re-irradiation could achieve successful local salvage in a substantial number of patients with early recurrence, but late complications did occur. Furthermore, high incidence of failure at other sites was observed. PMID- 8344846 TI - Re-irradiation of laryngeal carcinoma--techniques and results. AB - PURPOSE: Occasionally in the long-term survivors of early carcinoma of the larynx, following radiation therapy a second carcinoma may arise from the previously irradiated larynx. Traditionally, management of such lesions is by non radiation means in the belief that a further full course of radiation therapy is not possible and may exceed the tolerance of the normal laryngeal structures. Unfortunately, surgical treatment of the second carcinoma is often either total or partial laryngectomy which may not be acceptable to the patients and therefore radiation therapy is used as an alternative. METHODS AND MATERIALS: This paper presents our experience in re-irradiation of laryngeal carcinomas arising from the previously irradiated larynx. As of October 1992 a total of 20 patients were available for evaluation. Most patients had Stage I and II laryngeal carcinoma and received high doses of re-irradiation ranging from 60 to 70 Gy either by conventional or accelerated hyperfractionation schemes. RESULTS: The 5-year actuarial local control and survival rates were 60 to 93%, respectively. The majority of the survivors had relatively normal and functional larynges. Those who failed locally had total laryngectomy without significant postoperative complications. CONCLUSION: With this information the radiation tolerance of laryngeal structures is found to be much higher than commonly believed and re irradiation for early carcinoma of the larynx is possible and proved to be a useful alternative to surgery and laryngectomy is therefore reserved for failure. The techniques of re-irradiation will be discussed. PMID- 8344847 TI - Computed tomography evaluation of neck node metastases from nasopharyngeal carcinoma. AB - PURPOSE: To study the role of computed tomography in the pre-therapy evaluation of nasopharyngeal carcinoma. METHODS AND MATERIALS: The computed tomography of 119 new patients of nasopharyngeal carcinoma were evaluated independent of clinical findings for neck node metastases, and then compared with clinical findings. Contrast enhanced axial scans were obtained at 5 mm intervals with the infraorbitomeatal line parallel to the gantry. Scans were obtained from the supra sellar cistern to the C5 or C6 vertebra for the evaluation of the base of skull, nasopharynx, paranasopharyngeal space and the upper and mid neck. RESULT: The present study confirmed the disparity of nodal extent documented by clinical palpation and computed tomography. Of the 37 patients who have no clinically palpable node (N0), computed tomography showed nodal involvement in 11 (29.7%) of them, and they were up-staged from N0 to N1. Computed tomography showed multiple or bilateral nodes in seven (58.3%) of the 12 patients with AJC N1 disease and they were hence up-staged to N2. All together, there were 28 (23.5%) patients who have no computed tomography evidence of nodal involvement by tumor. In agreement with clinical experience, the most commonly involved nodal groups were the upper internal jugular and upper spinoaccessary, followed by the lateral retropharyngeal. The percentage of nodes which were not clinically palpable was roughly the same for different regions (15-30%), except, as expected, that all the retropharyngeal nodes were not palpable. The risk of harboring retropharyngeal node was proportional to the size of the largest node in the ipsilateral neck. CONCLUSION: A significant proportion of patients with clinically negative neck (N0) or AJC N1 disease will be upstaged by computed tomography, thus supporting its routine use in pre-therapy evaluation of nasopharyngeal carcinoma. PMID- 8344848 TI - In vivo measurement of the potential doubling time by flowcytometry in oropharyngeal cancer treated by conventional radiotherapy. AB - PURPOSE: Experimental and clinical studies suggest that the pre-treatment potential doubling time could be predictive of tumor control in patients treated by conventional radiotherapy and could help to identify the rapidly growing tumors for which accelerated radiotherapy is required. METHODS AND MATERIALS: To test this hypothesis, we studied prospectively 48 patients with a squamous cell carcinoma of the oropharynx and treated by conventional radiotherapy (70 Gy/7 weeks). The duration of S phase, the labeling index and the potential doubling time were obtained by flowcytometry measurements of a tumor biopsy obtained after injection of 200 mg bromodeoxyuridine to the patient. RESULTS: Three parameters were significantly associated with an increased risk of relapse namely the tumors size (T4; p < 0.01), the nodal status (> or = N2; p < 0.05) and the site of the primary within the oropharynx (p = 0.08). The S phase, labeling index, DNA index and potential doubling time were not significantly associated with an increased risk of relapse. However when considering only the T2 subgroup of patients, high labeling indexes and short potential doubling time were associated with an increased risk of relapse: the mean pre-treatment potential doubling time of the tumors which relapsed was 3.21 versus 5.5 days when there was no evidence of local relapse (p < 0.05). The mean labeling index for the group of tumors associated with a tumor recurrence was 11.7% compared to 7.3% when there was no evidence of relapse (p = 0.02). CONCLUSION: Factors other than proliferation play a role in determining the outcome of oropharyngeal cancers treated by conventional radiotherapy. However there was a significant correlation between short potential doubling time, high labeling index and tumor recurrence in the T2 subgroup of patients. The finding of significance for potential doubling time and labeling index in the T2 subset of tumors may be a reflexion of the more homogeneous nature of these tumors with regard to prognostic variables. PMID- 8344849 TI - Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: a phase I-II study. AB - PURPOSE: Hyperthermia is now being widely used to treat clinical malignancies especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplatin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. METHODS AND MATERIALS: Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5 degrees C for 30 min). RESULTS: Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in our previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systemic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, we observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. CONCLUSION: The study confirms the feasibility of the combination of cisplatin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors. PMID- 8344851 TI - Mathematical models of marrow cell kinetics: differential effects of protracted irradiations on stromal and stem cells in mice. AB - It is known that hematopoiesis is supported by bone-marrow stem cells, but those cells must seed and grow on a stromal microenvironment. Typically, studies have shown that a surviving fraction of about 30 hematopoietic stem cells (HSCs) (i.e., about 0.04%) correspond to the LD50, although other studies have shown that marrow can repopulate from a single viable cell under strong regiments of antibiotics and infusions of irradiated blood elements. PURPOSE: This paper describes comparisons between our results (from maximum-likelihood estimation techniques for cellular damage, repair, and compensatory repopulation) and published experimental data on marrow stromal cells. METHODS AND MATERIALS: After biophysical consideration of the rate constants that were derived by maximizing the likelihood function (a consideration necessary to extend the model to cell populations not indicated by the model as "critical" for recovery), the rate constants for cellular damage to stem cells are fitted to experimental data. Rate constants for repair and proliferation of stem cells are assigned based on published data on repair/proliferation half-times, and these assignments affect the evaluation of the rate constants for cellular damage. From the two models, that is one for "critical" cells (having radiosensitive and repopulation characteristics similar to stromal cells) and another for stem cells, effects on two cell populations of different radiosensitivities and repopulation rates can be demonstrated for complex schedules of protracted irradiations which could reduce either cell population below a critical need for marrow repopulation. RESULTS: Our analysis of animal mortality data has indicated that recovery of an animal from potentially lethal irradiation is dominantly regulated by cells with survival and repopulation characteristics similar to those of stroma cells. CONCLUSION: In contrast to the surviving fraction of hematopoietic stem cells, it appears that the probability of an animal's recovery is high if the "critical" population of cells is above 1% (our "best" maximum likelihood estimate, from mouse data, with the corresponding lower confidence bound at about 0.2%). Of course, a few stem cells--perhaps only one--must maintain a potential for repopulation of blood and marrow. PMID- 8344850 TI - Combined radiotherapy and chemotherapy in the management of local-regionally advanced vulvar cancer. AB - PURPOSE: To determine, in a retrospective single institutional study, the role of concurrent radiotherapy and chemotherapy in the treatment of local-regionally advanced vulvar cancer. METHODS AND MATERIALS: From 1984 to 1991, 20 patients with locally extensive primary or recurrent carcinoma of the vulva were treated with initial combined radiotherapy and chemotherapy. Seven patients had Federation Internationale de Gynecologie et d'Obstretrique Stage III disease, 10 had Stage IV disease, and three were treated for recurrent disease. None of these patients were considered candidates for primary radical vulvectomy and groin node dissection. Median radiation doses to regions of microscopic disease and gross tumor were 40 Gy (range 30-54 Gy) and 54 Gy (34-70.4 Gy), respectively. All patients received 2 or 3 cycles of 5-Fluorouracil concurrently with radiotherapy. In addition, five patients received Cis-platinum, and one Mitomycin-C. Median at risk follow-up interval was 37 months. RESULTS: Ten patients had complete resolution of tumor to initial chemoradiotherapy, and eight of these have remained free of tumor relapse. Eight other patients had partial responses, with tumor bulk reduced by > 50%, while the remaining two patients had local regionally progressive disease. Six of the patients with partial responses had residual tumor successfully resected, although four subsequently recurred. For the entire group of 20 patients, the actuarial 3- and 5-year local control rates were 48% each, and the corresponding disease-specific survival rates were 59% and 49%. There was a suggestion that better local control was obtained in patients who received gross tumor radiation doses > or = 50 Gy. Skin reaction was the major acute toxicity and responded well to conservative management. Long-term sequalae were limited to skin and subcutaneous atrophy. CONCLUSION: These results indicate that initial combined radiotherapy and chemotherapy is effective in the management of advanced vulvar cancer. PMID- 8344852 TI - Expression of p210 bcr/abl increases hematopoietic progenitor cell radiosensitivity. AB - PURPOSE: The cytogenetic finding of the Ph1+ chromosome and its molecular biologic marker bcr/abl gene rearrangement in cells from patients with chronic myeloid leukemia are associated with a proliferative advantage of the Ph1+ clone in vivo. Although the transition to the acute terminal phase or blastic crisis is often associated with additional cytogenetic abnormalities, the molecular events which correlate the initial cytogenetic lesion with the terminal phase are poorly understood. Defective cellular DNA repair capacity is often associated with chromosomal instability, increased mutation frequency, and biologic alterations. METHODS AND MATERIALS: We, therefore, tested whether the protein product of the bcr/abl translocation (p210) could alter DNA repair after gamma-irradiation of murine cell lines expressing the bcr/abl cDNA. RESULTS: The 32D cl 3 parent, 32D cl 3 pYN (containing the control vector plasmid) and each of two sources of 32D cl 3 cells expressing p210 bcr/abl cDNA (32D-PC1 cell line and 32D-LG7 subclone) showed a D0 of 1.62, 1.57, 1.16, and 1.27 Gy, respectively. Thus, expression of the p210 bcr/abl product induced a significant (p < 0.05) increase in radiosensitivity at the clinically relevant radiation therapy dose-rate (1.16 Gy/min). The increased radiosensitivity of p210 bcr/abl expressing cells persisted if cells were held before plating in a density-inhibited state for 8 hr after gamma-irradiation, indicating little effect on the repair of potentially lethal gamma-irradiation damage. The IL-3 dependent parent 32D cl 3 cells demonstrated programmed cell death in the absence of growth factor or following gamma-irradiation to 200 cGy. Expression of bcr/abl cDNA in the 32D-PC1 and 32D LG7 sub clones abrogated IL-3 requirement of these cell lines and inhibited gamma irradiation induced programmed cell death. CONCLUSION: These data suggest a role for bcr/abl p210 in amplifying gamma-irradiation DNA damage or broadly inhibiting DNA repair, conditions that may stimulate further cytogenetic alterations in hematopoietic cells. PMID- 8344853 TI - The differential induction of collateral resistance to 62.5 MeV (p-->Be+) neutrons and 4 MeV photons by exposure to cis-platinum. AB - PURPOSE: To determine the relative sensitivity to cis-platinum, 4 MeV photons and 62.5 MeV (p-->Be+) neutrons in five human tumor cell lines, and their cis platinum resistant variants. METHODS AND MATERIALS: The degree of cross resistance of five human in-vitro cell lines to photons or fast neutrons was analysed for both cisplatinum-sensitive and resistant variants. RESULTS: The development of acquired cis-platinum resistance conferred collateral resistance to 62.5 MeV (p--Be+) neutrons in all five cell lines, but did not consistently decrease the photon sensitivity of these same cells. CONCLUSION: The reduction in photon and neutron sensitivity following the development of acquired cis-platinum resistance may possibly be regulated by different mechanisms. The reduction in neutron sensitivity was primarily due to a 1.3-1.7 fold reduction in the magnitude of the initial slope (alpha), which was independent of the degree of platinum resistance induced, suggesting a non-stochiometric relationship between the mechanisms responsible for acquired cis-platinum, and 62.5 MeV (p-->Be+) neutron resistance. PMID- 8344854 TI - The management of desmoid tumors. AB - PURPOSE: To determine the efficacy of different treatment modalities for desmoid tumors. MATERIALS AND METHODS: We reviewed the treatment of 40 patients with histologically confirmed desmoid tumors seen at Duke University Medical Center between 1974 and 1990. RESULTS: Radiotherapy was administered to 16 patients (Group I)--14 with recurrent disease s/p surgery and in two as initial treatment. The average size of the irradiated lesions was 9.3 +/- 3.9 X 8.4 +/- 3.5 cm. With a median follow-up of 57.5 months and a median administered dose of 5400 cGy (mean 5286 cGy, range 4960-5620 cGy), local control has been obtained in 15/16 patients (94%). Complete regression (5/16), partial regression (5/16), or stable disease (5/16) was produced in 15 patients while one patient failed and was salvaged via gross total resection. Continued regression has been seen up to 60 months after treatment. Fourteen patients underwent primary gross total resection and two underwent subtotal resection (Group II). None received post-operative radiotherapy. Three of 14 patients (21%) recurred after gross total resection. All three were salvaged with subsequent gross total resection. After subtotal resection, 2/2 patients recurred. With a mean follow-up of 52 months, 14 patients are without evidence of disease, one is dead with disease (unrelated cause of death), and one was lost to follow-up after recurrence. Eight patients have been treated with combinations of chemotherapy, NSAIDS, anti-estrogens, and immunotherapy with mixed results (Group III). A subset of seven patients with retroperitoneal disease taken from all three groups had large tumor burden (mean size 17 X 15 cm), an infiltrative nature, as well as a difficult location. The disease was surgically resectable in three patients. One is without evidence of disease 9 years after gross total resection alone. Disease has been stabilized with radiotherapy in the other two patients after multiple unsuccessful surgical resections. Of four patients with unresectable disease, two are dead of disease, one died of unrelated causes with disease, and regression of disease was obtained in the other with Gamma-interferon after unsuccessful treatment with tamoxifen and vincristine, doxorubicin, and cyclophosphamide chemotherapy. CONCLUSION: Gross total resection is the indicated initial therapy, if it can be performed without significant disfigurement. Radiotherapy is also excellent for obtaining local control, even in patients with a large burden of recurrent disease. Doses in the range of 50 to 55 Gy give a chance of local control equal to that obtained with higher doses previously reported. PMID- 8344855 TI - Intraoperative radiotherapy in locally advanced recurrent colorectal cancer. AB - PURPOSE: In an effort to promote local control and improve quality of life in patients with recurrent colorectal cancer, a multimodality approach has been used. METHODS AND MATERIALS: Twenty-seven patients were treated with moderate doses of pre/postoperative radiotherapy with/without simultaneous systemic chemotherapy, surgical re-resection and IORT electron boost over areas at high risk for local recurrence. RESULTS: The 2-year actuarial disease-free and local relapse-free survival for the entire group were 14% and 26%, respectively. The most important factor predicting a favorable outcome was the radicality of surgical procedure. The determinate local control rate and the actuarial 2-year local relapse-free, and disease-free survival for patients undergoing complete resections were 50%, 56%, and 34%, respectively, whereas for patients undergoing partial resections these figures were 16%, 13%, and 6%. The radicality of surgical procedure was influenced by both tumoral size and previous treatment with irradiation. Complete resection rate was higher in patients with tumors less than 5 cm vs. more than 5 cm (40% vs. 22%), and in patients without previous radiotherapy versus those with previous radiotherapy (40% vs. 28%). Distant metastasis rate was high (41%). The most significant toxicities attributable to the whole treatment protocol were enteritis (37%), hydronephrosis (30%), and pelvic neuropathy (52%). CONCLUSION: Currently, our policy is to recommend IORT in patients with "favorable factors" such as: absence of previous pelvic radiotherapy, single previous surgical procedure, and complete resections. PMID- 8344856 TI - Objective decision-making following a portal film: the results of a pilot study. AB - PURPOSE: To discriminate between random and systematic treatment setup errors using portal films. METHODS AND MATERIALS: A bi-dimensional analytic techniques using multiple analyses of variance based on Hotelling's T2 statistics to derive numerical and graphical measures of daily portal film accuracy and precision has been trialed using 88 daily portal films from seven patients' treatment. RESULTS: A demonstration is provided of how a reasonable approximation of random variation from the intended (Simulator) field center, and systematic displacement of the mean position of the portal film centers may be derived from a minimum number of portal films. If a random error as great as 10 mm exists, at least six or seven portal films are considered necessary to reliably detect and quantify the size of a systematic error. CONCLUSION: Our results suggest that a modest systematic error could go undetected until the end of a 5 or 6 week course of treatment if only one portal film is obtained each week. A greater number of portal films should be performed during the first week of treatment to reduce the frequency of such errors. Efforts to separate and quantify both random and systematic errors in setup are worthwhile and will lead to improvements in outcome at the individual patient level and at a departmental level in the development of quality assurance programs. PMID- 8344857 TI - A new technique for positioning tangential fields. AB - PURPOSE: A technique that eliminates the use of a mechanical "breast-bridge" for positioning tangential fields for treatment of the intact breast or chest wall has been developed. METHODS AND MATERIALS: Treatment set-up parameters are determined using measuring capabilities (gantry angles and source-skin distances) available on a standard simulator unit. A programmable scientific calculator is used to determine field geometry from polar coordinates for various points on the patient's skin. The calculator program determines the field size, a depth and lateral shift from a skin reference point to the isocenter for the tangential fields, and the gantry angles. The program provides additional information which facilitates the simulation process: First, the coordinates of the isocenter for the tangential fields are expressed relative to couch coordinates for an initial arbitrary isocenter so that the "auto go to" capability available on some simulators can be used. Second, the coordinates of the medial and lateral entry points can be edited when the first set of tangents are not accepted. This part of the program allows quick and efficient adjustment of the fields to obtain adequate treatment volume coverage and a minimum of irradiated lung or heart. RESULTS: Simulation of more than 300 patients has shown the technique to be a practical and efficient method for positioning tangential fields for breast or chest wall irradiation. CONCLUSION: The technique described here takes full advantage of the capabilities of the new generation of computer controlled simulators, and offers an alternative to previous methods employing a mechanical "breast-bridge." PMID- 8344858 TI - Tolerances in setup and dosimetric errors in the radiation treatment of breast cancer. AB - PURPOSE: Treatment failure in radiation therapy, as well as unexpected complications, can be associated with set up changes or variations that can cause deviations from the prescribed radiation dose distribution both inside and outside the target volume. The effect of various deviations from the planned setup on the delivery of the prescribed radiation dose to the desired treatment volume was studied. METHODS AND MATERIALS: Adding a second simulation was investigated as means of minimizing setup changes on treatment. The first simulation was used for planning the treatment and the second simulation was essentially a mock treatment. Dosimetric evaluations based on dose volume histograms were analyzed for each deviation in the setup. RESULTS: In 95% of the patients, the frequency of the changes in the setup parameters between the second simulation and the treatment setup were reduced significantly from the changes that occurred between the first simulation and the second simulation. The changes in isocenter coordinates up to +/- 1.0 cm have minimal effects (+/- 2%) on the dose distributions. Gantry angle variations up to +/- 4 degrees produce a change of less than +/- 5% in the dose distribution within the target volume. However, this angular variation resulted in additional tissue irradiation outside of the desired treatment field (about 10 cm3 for a large patient). A gantry angle variation of +/- 6 degrees can change the volume of tissue that receives the prescribed dose by at least +/- 10%. In addition, such a change can increase the volume of tissue outside the desired treatment field that is irradiated. CONCLUSION: It is concluded that individually, deviations in one of the parameters from the planned setup of +/- 1.0 cm in isocenter position and +/- 4 degrees in gantry angle do not produce significant deviations from the planned dose distribution. However, a significant change in dose distribution is observed if the setup parameters are concurrently changed. A second simulation may minimize the deviations of the treatment setup from the planned setup and maximize the precision in dose delivery to the target volume. PMID- 8344859 TI - Analysis of temperature distributions of interstitial hyperthermia using a hot water system. AB - PURPOSE: Interstitial hyperthermia is being increasingly used as an adjunct to brachytherapy in the treatment of implantable tumors. Of the several interstitial hyperthermia systems available, perhaps the simplest to use are the circulating hot water systems. An analysis of the thermal distributions obtained during our initial experience with interstitial hyperthermia using steel needles and the KHS 9 hot water system was therefore undertaken. METHODS AND MATERIALS: Between September 1988 and June 1991, 23 patients were treated with interstitial Iridium 192 high dose-rate brachytherapy immediately followed by interstitial hot water hyperthermia. A total of 32 implants were performed in these patients, of whom 14 presented with primary anal carcinomas, six with recurrent gynecological tumors, and three with subcutaneous metastases from malignant melanoma. All but the patients with anal cancers had failed in previously irradiated sites. One or two heat treatments were delivered to each tumor with the goal to reach and maintain an intratumoral temperature 42.5 degrees C over a period of 40 min. Temperature measurements were carried out by mapping three-point thermocouple probes along the track of one or two needles parallel to the implanted needles. RESULTS: Minimum intratumoral temperatures exceeded 42.0 degrees C in 41%, 42.5 degrees C in 19%, 43.0 degrees C in 13%, and 44.0 degrees C in 3% of treatments. The average minimum, maximum, and mean intratumoral temperatures for all treatments were 41.7 degrees C, 43.5 degrees C, and 42.6 degrees C, respectively. CONCLUSION: The temperature profiles obtained in this series compare favorable to those reported in literature for radiofrequency local current field systems and suggest the hot water device may be an alternative heating method. It is relatively simple to use, does not require shielding of the treatment room, and can easily be adapted to currently used brachytherapy systems. Further patient accrual and longer follow-up will be needed to assess the clinical results in terms of tumor response and duration of response. PMID- 8344860 TI - Solid phantom material for the dosimetry of iodine-125 seed ophthalmic plaques. AB - PURPOSE: A tissue-equivalent solid phantom material, RE-1, closely simulating the radiological attenuation and scattering properties of the human eye for the iodine-125 photon spectrum and their Compton-scattered secondary photons, was fabricated on a polyethylene base with CaCO3 and MgO as inorganic additives. METHODS AND MATERIALS: A 24 mm diameter spherical phantom was made from 1.1 mm thick sheets of RE-1, and holes were drilled in which 1 mm3 TLD cubes were placed. RESULTS: The radial dose function g(r), which determines the dose profile on the transverse axis, was measured in a quasi-infinite phantom of RE-1. CONCLUSION: The values obtained deviate only slightly from those for a quasi infinite phantom made from water-equivalent material. PMID- 8344861 TI - Decision making for re-irradiation of nasopharyngeal carcinoma. PMID- 8344862 TI - Xanthofusin, an antifungal tetronic acid from Fusicoccum sp.: production, isolation and structure. PMID- 8344863 TI - Microbial conversion of avermectins by Saccharopolyspora erythrea: hydroxylation at C28. PMID- 8344864 TI - Studies on free radical scavenging substances from microorganisms. III. Isolation and structural elucidation of a novel free radical scavenger, resorstatin. PMID- 8344865 TI - On the structure of alisamycin, a new member of the manumycin class of antibiotics. PMID- 8344866 TI - Synthesis and antiviral activity of adenosine deaminase-resistant oxetanocin A derivatives: 2-halogeno-oxetanocin A. PMID- 8344867 TI - A new neuritogenetic compound BU-4514N produced by Microtetraspora sp. AB - A novel neuritogenetic compound BU-4514N was isolated from the fermentation broth of Microtetraspora sp. T689-92. It showed significant NGF-mimic activity and antibacterial activity against Gram-positive bacteria. Structural studies revealed that BU-4514N was a new chemotype antibiotic related to lydicamycin. PMID- 8344868 TI - Rumbrin, a new cytoprotective substance produced by Auxarthron umbrinum. I. Taxonomy, production, isolation and biological activities. AB - Rumbrin has been isolated from a fungus, Auxarthron umbrinum, by a screening program designed to find microorganism-produced cytoprotective substances. It was purified by use of column chromatography on silica gel, reversed phase HPLC and then isolated as fine red needles. Rumbrin prevented cell death caused by calcium overload and exhibited a potent inhibitory activity against lipid peroxidation. PMID- 8344869 TI - Rumbrin, a new cytoprotective substance produced by Auxarthron umbrinum. II. Physico-chemical properties and structure determination. AB - The structure of rumbrin (Fig. 1), a new cytoprotective substance, was elucidated by NMR spectral analysis. Rumbrin was found to possess a novel skeleton containing alpha-pyrone, tetraene and pyrrole moieties. PMID- 8344870 TI - Pyrrolostatin, a novel lipid peroxidation inhibitor from Streptomyces chrestomyceticus. Taxonomy, fermentation, isolation, structure elucidation and biological properties. AB - Pyrrolostatin, a new lipid peroxidation inhibitor, was isolated from the culture of Streptomyces chrestomyceticus EC40. The structure was determined to be 4 geranylpyrrole-2-carboxylic acid on the basis of its spectroscopic and physico chemical properties. Pyrrolostatin inhibited lipid peroxidation in rat brain homogenate. PMID- 8344871 TI - FR901277, a novel inhibitor of human leukocyte elastase from Streptomyces resistomycificus. Producing organism, fermentation, isolation, physico-chemical and biological properties. AB - A novel human leukocyte elastase inhibitor, FR901277 was discovered in the fermentation broth of Streptomyces resistomycificus No. 7622. FR901277 has a molecular weight of 961 and a molecular formula of C47H63N9O13. The mode of inhibition is competitive, with a Ki of 1.2 x 10(-8) M. Oral administration of FR901277 at doses from 32 to 320 mg/kg significantly prevented human leukocyte elastase-induced foot edema in mice. PMID- 8344872 TI - Bequinostatins A and B new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. Production, isolation, structure determination and biological activities. AB - New benzo[a]naphthacenequinone metabolites, designated bequinostatins A and B, have been isolated from the culture broth of the benastatin-producing strain Streptomyces sp. MI384-DF12. The structures of bequinostatins A and B were determined by spectral analyses to be 5,6,8,13-tetrahydro-1,6,7,9,11-pentahydroxy 8,13-dioxo-3- pentylbenzo[a]naphthacene-2-carboxylic acid and 2 decarboxybequinostatin A, respectively. Bequinostatin A showed considerable inhibitory activity against human pi class glutathione S-transferase (GST pi). PMID- 8344873 TI - Verucopeptin, a new antitumor antibiotic active against B16 melanoma. I. Taxonomy, production, isolation, physico-chemical properties and biological activity. AB - A new antitumor antibiotic verucopeptin was isolated from the culture broth of Actinomadura verrucosospora Q886-2. It should potent cytotoxicity and specific in vivo activity against B16 melanoma. Maximum T/C value (162%) was obtained by Q1D x 1 treatment schedule. PMID- 8344874 TI - Verucopeptin, a new antitumor antibiotic active against B16 melanoma. II. Structure determination. AB - The structure of a new antibiotic verucopeptin has been determined by the spectroscopic analyses and chemical degradation studies. It is a 19-membered cyclodepsipeptide which is structurally related to azinothricin and A83586C. PMID- 8344875 TI - Respinomycins A1, A2 B, C and D, a novel group of anthracycline antibiotics. I. Taxonomy, fermentation, isolation and biological activities. AB - Respinomycins are a novel group of anthracycline antibiotics produced by Streptomyces xanthocidicus. Respinomycins A1, A2, B, C and D were isolated by EtOAc extraction, silica gel column chromatography, centrifugal partition chromatography and preparative silica gel thin layer chromatography. Respinomycins A1 and A2 induced the terminal differentiation of human leukemia K 562 cells. PMID- 8344876 TI - Respinomycins A1, A2, B, C and D, a novel group of anthracycline antibiotics. II. Physico-chemical properties and structure elucidation. AB - Respinomycins A1, A2, B, C and D were revealed to be novel anthracycline antibiotics with molecular formulae of C51H72N2O20, C43H58N2O15, C35H43NO14, C36H45NO14 and C51H70N2O22, respectively. Their structures were determined by means of 1H-1H COSY, 13C-1H COSY and HMBC spectra. The structure of the aglycone of respinomycins was unambiguously determined by LSPD experiments and NOESY. The common skeleton of respinomycins is a new type and is distinguished from that of the nogalamycin group. PMID- 8344877 TI - BU-4794F, a new beta-1,3-glucan synthase inhibitor. AB - New beta-1,3-glucan synthase inhibitor (BU-4794F) was isolated from the culture broth of Gilmaniella sp. FA4459. Structural studies indicated that it was a novel member of the papulacandin group of antibiotics. PMID- 8344878 TI - Lachnumon and lachnumol a, new metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. I. Producing organism, fermentation, isolation and biological activities. AB - Several chlorinated metabolites with nematicidal, antimicrobial, and cytotoxic activities were isolated from submerged cultures of the ascomycete Lachnum papyraceum. Three compounds were identified as (+)-mycorrhizin A (3), (+) chloromycorrhizin A (4) and (+)-dechloromycorrhizin A (5). The occurrence of 5 as a natural product is new. Two compounds, lachnumon (1) and lachnumol A (2), were found to be new fungal metabolites with cytotoxic, nematicidal and antimicrobial activities. PMID- 8344879 TI - Lachnumon and lachnumol a, new metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. II. Structural elucidation. AB - The structures of two new biologically active chlorinated metabolites isolated from submerged cultures of the ascomycete Lachnum papyraceum have been elucidated by NMR and mass spectroscopy. The compounds, lachnumon (1) and lachnumol A (2), which structurally are related with mycorrhizin A that also is produced by the fungus, contain an unusual chlorinated epoxide group. PMID- 8344880 TI - Chemical transformation of gilvocarcin V. Modification of the side-chain. AB - Gilvocarcin V was chemically transformed to alter its biological activities as well as its solubility by mainly focusing on the vinyl side chain. The oxirane and oxime derivatives showed slightly decreased in vivo antitumor activity, while the aminoethylmorpholine derivative turned out to be soluble in some organic solvents. PMID- 8344881 TI - Synthesis and structure-activity relationships of new cephalosporins with aminoimidazoles at C-7. Effect of the pKa of the C-7 aminoimidazole on antibacterial spectrum and beta-lactamase stability. AB - Cephalosporins with new aminoimidazole heterocycles at C-7 have been synthesized by reaction of anti-alpha-aminooximes with C-7 dihaloisocyanocephalosporins esters or by direct condensation of 2-fluoroimidazoles with C-7 aminocephalosporins esters. These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram-positive organisms with a good beta-lactamase stability. Activity is discussed in terms of its relationship to the pKa of the C-7 aminoimidazole heterocycle, basic C-7 aminoimidazole residues gave cephalosporins with the best beta-lactamase stability but the poorest activity against Gram-positive organisms. An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in some compounds of this series. PMID- 8344882 TI - Role of autologous bone marrow transplantation for patients with acute and chronic leukemias. AB - Autologous bone marrow transplantation has been increasingly used as effective curative therapy for patients with acute myelocytic leukemia or acute lymphoblastic leukemia who are not candidates for allografting. Its potential role for patients with chronic myelocytic leukemia is considered investigational; however, recent advancements in stem cell separation may make autologous transplantation an attractive alternative for this disease as well. The timing of the autologous transplant and the role of marrow purging are discussed in depth. In addition, post-transplant immune modulation and the use of growth factors and other cytokines following autologous reinfusion are currently being investigated. PMID- 8344884 TI - Role of autotransplantation in neuroblastoma. AB - Neuroblastoma is the most enigmatic disease treated by pediatric oncologists. The same pattern of apparent metastatic spread is associated with a high rate of spontaneous regression in children under 1 year of age (stage IVS) but an invariably fatal course in older children. For these children with truly advanced neuroblastoma, recent studies have demonstrated that the possibility of complete remission and disease-free survival is increased with more intensive conventional combination chemotherapy. Supportive care with autologous marrow has enabled further significant dose escalation of cytotoxic therapy active against neuroblastoma, resulting in disease-free survival in between 25% and 50% of patients at 2 years, an improvement over historical experience with conventional chemotherapy. The development of more effective cytotoxic combinations active against neuroblastoma, improvements in ex vivo techniques to purge marrow of neuroblastoma cells, and the application of cytokines to hasten marrow recovery should further enhance the effectiveness of autotransplantation in the treatment of advanced neuroblastoma and further improve the chances for complete remission and longer remission duration. Whether this improved remission induction and duration will translate into an increased cure rate remains to be determined. Parallel advances in therapies not involving autologous marrow support will undoubtedly modify the role of autotransplantation in neuroblastoma. Currently, however, autotransplantation offers one potential solution to a major challenge in the treatment of advanced neuroblastoma--obtaining and maintaining complete remissions--and a promising basis for future therapeutic studies. PMID- 8344883 TI - Role of autotransplantation in Hodgkin's disease. AB - Autologous bone marrow transplantation offers the opportunity for long-term disease-free survival in patients with Hodgkin's disease who might be considered incurable with other treatments. The appearance of late relapses in some reports is worrisome, but it is hoped that the majority of long-term survivors are indeed cured. Fundamental questions remain concerning the best conditioning regimen, the best rescue source, the optimal timing of transplantation, and ultimately whether transplantation is better than conventional salvage techniques. Some of these answers may be provided if long-term follow-up studies are reported and results are analyzed with reference to known prognostic factors. Ultimately, prospective trials will be needed to more clearly define the role of transplantation in Hodgkin's disease. It is hoped that ongoing trials will lead to higher remission rates, lower relapse rates, and diminished transplant-related mortality. PMID- 8344885 TI - Role of autotransplantation in treatment of other solid tumors. AB - This article reviews the use of high-dose chemotherapy with autologous bone marrow support for a variety of solid tumors. A major feature of the vast majority of studies examined is the high response rates achieved with intensive therapy when compared with those reported with standard chemotherapy. If these rates can be obtained in patients with diseases refractory to standard therapy, then applying the same treatment earlier in the disease course may produce more durable antitumor effects. PMID- 8344887 TI - Infectious complications during autotransplantation. AB - Bacterial and fungal infections are the most common cause of morbidity and mortality following autologous marrow transplant. An understanding of defects in host defense and the sources of bacterial and fungal infections allows a rational approach to controlling infections through prophylactic and empiric treatment. Recent availability of growth factors, broad-spectrum antibiotics, monoclonal antibodies to endotoxin, new antiviral agents, and new antifungal agents have enhanced our ability to successfully support patients through high-dose therapy and autologous stem cell reinfusion. PMID- 8344886 TI - Developments in purging in autotransplantation. AB - High-dose therapy and bone marrow transplantation has been shown to be a potentially curative modality for patients with hematologic malignancies. Several obstacles to the use of this approach include the availability of histocompatible siblings and the increased toxicity even in HLA-matched patients owing to graft versus-host disease and interstitial pneumonitis. The use of autologous marrow in support of high-dose therapy has lower toxicity; however, there is the issue that residual tumor cells may be reinfused into the patient. There are several laboratory studies demonstrating that residual tumor cells persist in the marrow despite histologic remission. In addition, case reports suggest that contaminated marrow has led to widespread early relapse owing to reinfusion of tumor cells. A variety of techniques have been developed that can deplete up to 5 logs of tumor cells from the marrow. These techniques include very specific immunologic as well as less specific pharmacologic purging. Both approaches have been refined so that normal hematopoietic stem cell reconstitution is relatively preserved. Although a large number of studies have been reported that have utilized ex vivo marrow purging, few have examined whether there has been an impact on disease-free survival. Although randomized studies have not been performed to date, several recent studies in ANLL and B-cell NHL strongly suggest that there is a relationship between the quality of elimination of the disease ex vivo in the marrow and disease-free survival. With further improvements in marrow treatment, whereby all detectable cells are depleted, as determined by highly sensitive molecular biologic techniques, and randomized trials involving purged and unpurged BM, the question of the impact of ex vivo marrow treatment can be better answered. PMID- 8344888 TI - Role of cytokines in autologous bone marrow transplantation. AB - High-dose chemotherapy with autologous bone marrow support has been increasingly used in the treatment of malignant disease. The use of hematopoietic colony stimulating factors (CSF), particularly when coupled with the use of CSF-primed peripheral blood progenitor cells, has enabled a substantial reduction in the duration of severe leukopenia and in the morbidity associated with bone marrow transplantation. Furthermore, their use has reduced resource utilization and hospital charges and has also permitted the performance of autologous bone marrow transplantation support largely on an outpatient basis. PMID- 8344889 TI - Mitochondrial transcription initiation. Variation and conservation. PMID- 8344890 TI - In vivo gene delivery. Efficient transfection of T lymphocytes in adult mice. AB - We have demonstrated that a single intraperitoneal injection of cationic liposomes complexed to a chloramphenicol acetyltransferase (CAT) gene expression plasmid can transfect the majority of splenic Thy 1.2+ T lymphocytes, as well as significant numbers of bone marrow-derived hematopoietic cells, in adult mice. CAT activity was detected in the spleen for at least 2 weeks, and there was no evidence of treatment-related toxicity. Some degree of tissue-specific transgene expression was achieved by varying the cationic lipid used. PMID- 8344891 TI - The immunosuppressant rapamycin induces inactivation of p70s6k through dephosphorylation of a novel set of sites. AB - The immunosuppressant rapamycin selectively abolishes phosphorylation and activation of p70s6k/p85s6k at concentrations that either block or suppress cell growth. The four sites of phosphorylation associated with p70s6k/p85s6k activation all display Ser/Thr-Pro motifs and are closely clustered within a putative autoinhibitory domain of the enzyme. To produce a constitutively active, rapamycin-resistant form of the kinase, these four sites were converted to either Asp or Glu. When overexpressed in human 293 cells, the activity of the mutant is similar to that of the parent enzyme, under conditions where the parent is phosphorylated and active. Unexpectedly, however, the mutant remains sensitive to rapamycin and is inactivated in vitro by protein phosphatase 2A. Peptide maps reveal that rapamycin abolishes the activity of the overexpressed p70s6k through the dephosphorylation of a novel set of sites distinct from those associated with mitogenic activation. PMID- 8344892 TI - The photochemical reactions of sensory rhodopsin I are altered by its transducer. AB - The sopI gene, which encodes the phototaxis receptor sensory rhodopsin I (SR-I), was expressed in Halobacterium salinarium strains with chromosomal deletions of (i) sopI only or of (ii) the region containing sopI and htrI. The htrI gene encodes a transducer protein for SR-I signals. Transformation of the sopI deletion mutant containing the htrI gene by a multicopy expression plasmid for sopI results in normal physiological and photochemical properties of SR-I. Transformation by the same plasmid of the mutant lacking the htrI gene as well as sopI results in production of pigment with a normal absorption spectrum but altered photochemical properties, and no phototaxis by the transformants. Analysis of flash-induced absorbance changes shows that the transducer protein increases light-induced production of the photocycle intermediate S373, the SR-I signaling conformation, and modulates the rate of S373 return to the prestimulus state, rendering this return pH-independent. These effects are interpreted in terms of receptor/transducer interactions that influence proton transfer reactions occurring in the photoactive site. PMID- 8344893 TI - The DNA-binding subunit of human transcription factor IID can interact with the TATA box as a multimer. AB - Transcription initiation from eukaryotic protein-coding genes is a complex process that minimally requires RNA polymerase (pol) II (B) and at least seven general transcription factors. The 38-kDa subunit (TBP) of the human general transcription factor TFIID recognizes the TATA sequence element and initiates the assembly of the other general transcription factors and RNA pol II. It is believed, based on experiments with yeast recombinant protein, that TBP binds as a monomer to DNA. Using purified recombinant human TBP protein we find that TBP interacts with the TATA element as both a monomer and a dimer. The multimeric binding of TBP to DNA revealed by this study has important implications for the role of TBP in transcription initiation and suggests novel mechanisms whereby other transcription factors may interact with a RNA pol II preinitiation complex. PMID- 8344894 TI - A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer's disease. AB - Abnormalities of zinc metabolism occur in Alzheimer's disease (AD), a condition where pathological catabolism of the amyloid protein precursor (APP) causes cerebral beta A4 amyloidosis. An association between zinc and APP metabolism was sought by studying the binding of 65Zn2+ to APP. 65Zn2+ bound in a rapid, saturable, and specific manner (KD = 764 nM). A novel zinc binding motif, strongly conserved between members of the APP family, was located between the cysteine-rich and negatively charged domains of the protein. Zinc increased binding of APP to heparin and has been shown to potentiate the inhibition of coagulation factor XIa by an APP isoform containing a Kunitz-type inhibitory domain (Komiyama, Y., Murakami, T., Egawa, H., Okubo, S., Yasunaga, K., and Murata, K. (1992) Thromb. Res. 66, 397-408) situated near the zinc binding region. Zinc is a factor that modulates the functional properties of the substrate for beta A4 amyloidogenesis. PMID- 8344895 TI - Evidence from transgenic mice that glucose transport is rate-limiting for glycogen deposition and glycolysis in skeletal muscle. AB - A line of transgenic mice was constructed in which the human Glut1 glucose transporter is overexpressed in skeletal muscle. Overexpression of Glut1 protein was evident in epitrochlearis, extensor digitorum longus (EDL), and quadriceps muscles, and resulted in 6.6-7.4-fold elevations in basal glucose transport activity as measured in isolated muscles in vitro. The elevated glucose transporter activity in the skeletal muscles of transgenic mice was associated with a 10-fold increase in glycogen concentration in EDL and quadriceps muscles that was not due to an increase in muscle glycogen synthase activity or a decrease in glycogen phosphorylase activity. The increased glucose transport activity also resulted in a 2-fold increase in muscle lactate concentration, with no increase in muscle glucose 6-phosphate. Despite a slight (10%) increase in muscle hexokinase activity, there was a 4-fold increase in total muscle free glucose in transgenic mice, indicating that hexokinase becomes rate-limiting for glucose uptake when the rate of glucose transport is very high. These results demonstrate that the muscle glycogen content can be dramatically elevated by increasing the muscle Glut1 protein level and that glucose transport is a rate limiting step for muscle glucose disposal in normal, resting mice. PMID- 8344896 TI - Dephosphorylation and inactivation of the mitogen-activated protein kinase by a mitogen-induced Thr/Tyr protein phosphatase. AB - The activation of extracellular signal-regulated kinase (ERK) or mitogen activated protein kinase (MAPK) by a dual specific kinase, MEK (MAPK or ERK kinase), is a critical event in the mitogenic signal transduction pathway. However, little is known about the mechanism of ERK inactivation, which occurs after stimulation. In this report, we demonstrated that a dual specific protein phosphatase, HVH1 (human VH1 phosphatase homolog) whose expression is induced by mitogenic growth factors, specifically inactivates ERK. When several phosphoproteins were tested for recombinant HVH1, only MEK-activated ERK1 was dephosphorylated. HVH1 selectively dephosphorylated threonine and tyrosine residues but not serine residues of the activated ERK1. Inactivation of ERK1 by HVH1 could be reversed by MEK, suggesting that HVH1 dephosphorylates the same residues that are recognized and phosphorylated by MEK. Our results suggest that mitogenic growth factors transiently activate ERK (peak at 5 min followed by a rapid decline) by temporally activating MEK (the on signal) and inducing the expression of HVH phosphatase (the off signal). PMID- 8344897 TI - Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells. AB - Phorbol ester-sensitive and -resistant EL4 thymoma cell lines differ in their ability to activate mitogen-activated protein kinase (MAPK) in response to phorbol ester. Treatment of wild-type EL4 cells with phorbol ester results in the rapid activations of MAPK and pp90rsk kinase, a substrate for MAPK, while neither kinase is activated in response to phorbol ester in variant EL4 cells. This study examines the activation of MAPK kinase (MAPKK), an activator of MAPK, in wild type and variant EL4 cells. Phosphorylation of a 40-kDa substrate, identified as MAPK, was observed following in vitro phosphorylation reactions using cytosolic extracts or Mono Q column fractions prepared from phorbol ester-treated wild-type EL4 cells. MAPKK activity coeluted with a portion of the inactive MAPK upon Mono Q anion-exchange chromatography, permitting detection of the MAPKK activity in fractions containing both kinases. This MAPKK activity was present in phorbol ester-treated wild-type cells, but not in phorbol ester-treated variant cells or in untreated wild-type or variant cells. The MAPKK from wild-type cells was able to activate MAPK prepared from either wild-type or variant cells. MAPKK activity could be stimulated in both wildtype and variant EL4 cells in response to treatment of cells with okadaic acid. These results indicate that the failure of variant EL4 cells to activate MAP kinase in response to phorbol ester is due to a failure to activate MAPKK. Therefore, the step that confers phorbol ester resistance to variant EL4 cells lies between the activation of protein kinase C and the activation of MAPKK. PMID- 8344898 TI - Growth-dependent changes in arachidonic acid release from endothelial cells are mediated by protein kinase C and changes in diacylglycerol. AB - When stimulated, endothelial cells release arachidonic acid from phospholipids and oxidize it to eicosanoids. The rate-limiting step in this pathway is the initial release step, catalyzed by phospholipase(s), a process that exhibits growth-dependent changes. We examined the role of protein kinase C (PKC) as a regulator of this process. Activators and inhibitors of protein kinase C, used at different growth states, demonstrated distinct differences in their effects on arachidonic acid release, consistent with a growth-dependent change in PKC activity (with greater activity in proliferating cells compared with quiescent cells). Although immunoreactive PKC was slightly greater in the proliferating cells, there was a more striking redistribution of PKC activity between cytosol and membrane. To identify the cause, we measured the diacylglycerol (DG) content and found that DG concentrations decreased as cells progressed from preconfluence to confluence. Further studies demonstrated increases in DG kinase and DG lipase in confluent compared with preconfluent cells, consistent with the alterations in DG content. These findings suggest that growth-dependent changes in DG lipase and DG kinase activities regulate basal DG levels and PKC activity. The consequent alteration in PKC activity regulates the growth-dependent changes in arachidonic acid release. PMID- 8344899 TI - Biosynthesis of oligosaccharides in intact Golgi preparations from rat liver. Analysis of N-linked glycans labeled by UDP-[6-3H]N-acetylglucosamine. AB - During short incubations of a Golgi apparatus-enriched subcellular fraction from rat liver with UDP-[3H]GlcNAc, label is efficiently transferred to endogenous acceptors. Most of the macromolecular radioactivity is specifically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase, indicating that it is mainly associated with N-linked oligosaccharides. The glycoprotein acceptors are resistant to proteases unless detergent is added in amounts greater than the critical micellar concentration. This shows that the acceptors are within the lumen of intact compartments, which have the correct topological orientation expected for the Golgi apparatus in intact cells. Structural characterization of the radiolabeled N-linked oligosaccharides shows a variety of distinct neutral and anionic species. The neutral chains include bi-, tri-, and tetra-antennary molecules with terminal beta-[3H] GlcNAc residues. In vitro sialylation shows that some of the tetra-antennary chains have beta 1,3-linked Gal residues on their unlabeled antennae. An unknown modification appears to block the action of beta-galactosidase on these galactosylated oligosaccharides. Chasing the labeling reaction with a mixtures of UDP-Gal, CMP-Neu5Ac, and adenosine 3'-phosphate,5' phosphosulfate causes an increase in the percent of radiolabeled anionic oligosaccharides. Most of the negative charge is due to sialic acid (Sia), and some appears to be in phosphodiester-linked [3H]GlcNAc. The sialylated oligosaccharides are a mixture of bi-, tri-, and tetra-antennary species with 1-3 Sia residues, and some of the [3H]GlcNAc residues are directly covered with unlabeled Gal and Sia residues. This in vitro approach should recapitulate reactions that occur in the biosynthesis of N-linked oligosaccharides in the Golgi apparatus of the intact cell. Since the conditions during labeling do not permit inter-compartmental transport, the oligosaccharides produced should represent the biosynthetic capabilities of individual Golgi compartments. Evidence is presented for a functional association of GlcNAc transferases I, II, and alpha-mannosidase II, with separation from GlcNAc transferase IV and/or V. The structures also indicate co-compartmentalization of several GlcNAc transferase(s) with beta-galactosyltransferase(s) and sialyltransferase(s). The compartmental organization of the Golgi apparatus is discussed in light of these findings. PMID- 8344900 TI - Biosynthesis of oligosaccharides in intact Golgi preparations from rat liver. Analysis of N-linked glycans labeled by UDP-[6-3H]galactose, CMP-[9-3H]N acetylneuraminic acid, and [acetyl-3H]acetyl-coenzyme A. AB - When a rat liver Golgi apparatus-enriched subcellular fraction is incubated with UDP-[3H]Gal, CMP-[3H] Neu5Ac, or [acetyl-3H]acetyl (Ac)-CoA, label is efficiently transferred to endogenous acceptors, which are resistant to added proteases, unless detergent is added at a sufficiently high concentration. Thus, the acceptors are within the lumen of intact compartments of correct topological orientation, which are likely to be similar to those of the Golgi apparatus in the intact cell. In each case, approximately 90% of the macromolecular radioactivity is specifically released by peptide-N4-(N-acetyl-beta glucosaminyl)asparagine amidase digestion, as labeled N-linked oligosaccharides. Label from UDP-[3H]Gal is transferred to several distinct N-linked oligosaccharides, and many of these carry sialic acid (Sia) residues. This amount increases if the transfer reaction is chased with CMP-Neu5Ac. A major fraction of the [3H]Gal is directly "covered" with Sia residues, indicating that at least a portion of the beta-galactosyltransferase(s) are co-localized with one or more sialyltransferases. The majority of the [3H]Gal is found in a beta 1,3-linkage, rather than the more common beta 1,4-linkage. The N-linked oligosaccharides labeled by CMP-[3H] Neu5Ac carry labeled Sia residues in either alpha 2,3 or alpha 2,6 linkage, and showed a range of charge distribution. The transferred [3H]Neu5Ac is not O-acetylated even when Ac-CoA is added at saturating concentrations, implying that the sialyltransferases and the O acetyltransferase(s) are not functionally co-localized. However, approximately 20% of label released from N-linked oligosaccharides by sialidase does not co migrate with authentic Neu5Ac in high performance liquid chromatography analysis, indicating that transferred [3H] Neu5Ac is modified by unknown enzymes in the Golgi. Most of the [3H]acetate transferred from [acetyl-3H] Ac-CoA to N-linked oligosaccharides is on Sia residues that are exclusively alpha 2,6-linked, and is enriched on tri- and tetra-antennary chains that do not appear to carry any 2,3 linked Sia residues. These data indicate a restricted substrate preference of the O-acetyltransferase(s). About one-quarter of the [3H]acetate transferred is sialidase-resistant, indicating either transfer to monosaccharides other than sialic acid, or to sialidase-resistant sialic acids. While most of these sialidase-resistant oligosaccharides remain negatively charged, about 10% are neutralized by sialidase, confirming transfer of [3H]acetate to monosaccharides other than sialic acid. PMID- 8344902 TI - High levels of photosystem I subunit II (PsaD) mRNA result in the accumulation of the PsaD polypeptide only in the presence of light. AB - The light-regulated mRNA and polypeptide accumulation of the nuclear encoded subunit II (PsaD) of the photosystem I reaction center was studied during the greening of etiolated spinach seedlings. Upon exposure to continuous white light, the mRNA, detected at low levels in etiolated seedlings, accumulated in a specific pattern. In contrast, the PsaD subunit could not be detected in the etiolated seedlings; the polypeptide could first be detected in thylakoid membranes approximately 4 h after exposure to continuous light. A pulse of red light induced the expression of the PsaD mRNA, but the polypeptide could not be detected unless the seedlings were exposed to light. In the light (but not in the dark), the PsaD mRNA was found associated with the polysomal fraction. Taken together, the data suggest a dual regulatory mechanism in which both the level of mRNA and the presence of light control the accumulation of the PsaD polypeptide. PMID- 8344901 TI - The biosynthesis of oligosaccharides in intact Golgi preparations from rat liver. Analysis of N-linked and O-linked glycans labeled by UDP-[6-3H]N acetylgalactosamine. AB - Endogenous acceptors in a Golgi apparatus-enriched subcellular fraction from rat liver were labeled with UDP-[3H]GalNAc. The great majority of these acceptors were protected from protease degradation in the absence of detergent. These molecules are therefore present in intact vesicles of the correct topological orientation, which are likely to be similar to the Golgi compartments of the intact cell. Several distinct glycoproteins are labeled, but most are different from those labeled with UDP-[3H]GlcNAc. The enzyme peptide-N4(N-acetyl-beta glucosiminyl)asparagine amidase releases label from a few specific proteins, indicating that [3H]GalNAc is transferred to N-linked oligosaccharides. Both neutral and anionic N-linked oligosaccharides are found, the great majority of which do not bind to ConA-Sepharose. Most of the [3H]GalNAc found in neutral oligosaccharides is terminal and beta-linked. The negative charge on the anionic molecules is due to sialic acid, and phosphate. A major portion of the [3H] GalNAc in this fraction is acid labile, and is released with kinetics consistent with it being in a phosphodiester linkage. These results show the existence of a whole new class of GalNAc-containing N-linked oligosaccharides, and demonstrates that this in vitro approach can detect previously undescribed structures. O linked oligosaccharide biosynthesis was also studied in the same labeled rat liver Golgi apparatus preparations. beta-Elimination releases approximately 95% of the peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase (PNGase F) resistant label which, in the absence of other added nucleotides, is almost exclusively [3H] GalNAcitol. If other unlabeled sugar nucleotides and adenosine 3'-phosphate,5'-phosphosulfate are added during the chase period two anionic O linked oligosaccharides are synthesized, indicating that the UDP-GalNAc:peptide-N acetylgalactosaminyltransferase is at least in part functionally co-localized with enzymes that extend and modify O-linked oligosaccharides. PMID- 8344903 TI - Fluorescent pyrrole products from carbonyl-amine reactions. AB - The reaction of (E)-4,5-epoxy-(E)-2-heptenal with butylamine and glycine methyl ester produced brown macromolecular pigments, which showed fluorescent characteristics similar to lipofuscins. This polymerization reaction implies in the first step the formation of 1-alkyl-2-(1'-hydroxyalkyl)pyrroles (IV, VI). Compounds IV and VI have been isolated and characterized from the above reactions, and their structures confirmed with the synthesis of 2-(1' hydroxyethyl)-1-methylpyrrole (V). Compounds IV-VI resulted very unstable and even diluted solutions of them polymerized with time. The first step was the production of a dipyrrymethane VIII, which evolved more stable dipyrrylmethenes IX and X by intramolecular dehydration. These dimers continued polymerizing to produce 16H-tripyrrin derivatives XI and XII, and, in the next step, hexahydroglobins XIII and XIV. All these compounds have been characterized by 1H NMR and/or gas chromatography coupled with mass spectrometry or mass spectrometry. Additional polymerization produced higher molecular weight polymers that were the responsible for the brown color and the fluorescence. The above results suggest that the fluorescence produced by reaction between some oxidized lipids and amino acids may be related to polymerization more than to the formation of single structures. PMID- 8344904 TI - Membrane lipid regulation in Acholeplasma laidlawii grown with saturated fatty acids. Biosynthesis of a triacylglucolipid forming reversed micelles. AB - The membrane lipid composition in several strains of Acholeplasma laidlawii is regulated upon a change in the growth conditions. Monoglucosyldiacylglycerol (MGlcDAG) and diglucosyldiacylglycerol (DGlcDAG) are the most abundant lipids in the A. laidlawii membrane. A third glucolipid, 3-O-acyl monoglucosyldiacylglycerol (MAMGlcDAG) is synthesized by strain A-EF22 when the membrane lipids contain large amounts of saturated acyl chains. The lipid regulation can be understood from a simple theoretical model, in which the cells strive to maintain a balance between the lipids constituting a bilayer and those forming reversed non-lamellar liquid crystalline phases. Thus, the physical chemistry of membrane lipids, in particular their ability to form different aggregate structures, constitutes the basis for the lipid regulation, and therefore an understanding of the phase equilibria of membrane lipids is crucial. MGlcDAG and MAMGlcDAG isolated from A. laidlawii strain A-EF22 membranes were studied mainly by 2H NMR, 1H NMR, and 1H NMR diffusion measurements. MAMGlcDAG, containing 96 mol % saturated acyl chains formed a gel/crystalline phase up to about 80 degrees C, where a transition occurred to a reversed micellar (L2) phase. This is an unexpected finding for a membrane lipid. However, this lipid homogeneously mixes with the other membrane lipids at physiological temperatures. Previous and new data on MGlcDAG show that the lamellar phase is stabilized when the length and the degree of unsaturation of the acyl chains are decreased. The physicochemical properties of MAMGlcDAG and MGlcDAG were compared and found to be of great significance for the physiological regulation of the lipids in the membrane. MAMGlcDAG is synthesized under conditions when the phase equilibria of MGlcDAG are shifted from a non-lamellar toward a lamellar phase. Apart from MAMGlcDAG, MGlcDAG is the major lipid in A. laidlawii strain A-EF22 which is able to form reversed aggregate structures. MAMGlcDAG probably assists MGlcDAG in maintaining an optimal molecular packing, or negative curvature, of the lipids in the membrane. PMID- 8344905 TI - The gamma subunit of R-phycoerythrin and its possible mode of transport into the plastid of red algae. AB - R-phycoerythrin is the major light-harvesting pigment protein of most red algal phycobilisomes. It is composed of three pigmented polypeptide subunits, the alpha, beta, and gamma. While alpha and beta phycoerythrin subunits are each unique in the red alga Aglaothamnion neglectum, there are two different gamma subunits with distinct molecular masses. Both gamma subunits are pigmented by virtue of covalently attached linear tetrapyrroles. The amino acid sequence of one of the gamma subunits, as deduced from the nucleotide sequence of a cDNA clone, has no significant similarity to any known sequence in the data bases. This result is surprising, since the gamma subunit of phycoerythrin is thought to have a function that is similar to cyanobacterial linker polypeptides. The A. neglectum gamma subunit is synthesized as a 36-kDa precursor protein that is processed at the amino terminus to yield a 33-kDa mature protein. The amino terminal extension was able to direct the pea small subunit of Rubisco into isolated pea chloroplasts. This result suggests that red algae transport proteins into the plastid by a mechanism similar to that of higher plants. There are significant changes in levels of mRNA encoding the gamma 33 subunit when A. neglectum is grown under different conditions of illumination and in nitrogen deficient medium. These changes parallel those previously observed for transcripts encoding the alpha and beta phycoerythrin subunits. Hence, there may be coordinated expression of nuclear and plastid-encoded phycoerythrin subunit genes. PMID- 8344906 TI - A Kazal-type inhibitor with thrombin specificity from Rhodnius prolixus. AB - A thrombin-specific inhibitor with an apparent molecular mass of 11 kDa has been purified from the insect Rhodnius prolixus. Amino-terminal protein sequence analysis allowed the molecular cloning of the corresponding cDNA. The open reading frame codes for a protein of about 103 amino acid residues and displays an internal sequence homology of residues 6-48 with residues 57-101 indicating a two-domain structure. Based on the amino acid sequence the two domains exhibit high homology to protease inhibitors belonging to the Kazal-type family. Model building suggests that the first domain binds to the active site with residue His10 pointing into the specificity pocket. From gel filtration and tight-binding inhibition experiments the inhibitor appears to form 1:1 complexes with thrombin. Periplasma-directed heterologous expression of the rhodniin cDNA in Escherichia coli yields the intact thrombin inhibitor. Natural and recombinant rhodniin both display inhibition constants of about 2 x 10(-13) M. PMID- 8344907 TI - Toward an understanding of the biogenesis of the starch granule. Evidence that Chlamydomonas soluble starch synthase II controls the synthesis of intermediate size glucans of amylopectin. AB - Low starch mutants of Chlamydomonas reinhardtii were isolated after x-ray mutagenesis of wild-type strain 137C. The mutants accumulated 20-40% of the normal amount and displayed a 2-fold decrease of the total glycogen-primed soluble starch synthase activity. Three different mutant alleles of the st-3 gene were isolated that were characterized by similar defects and displayed a net increase in amylose content. Amylose-primed synthesis of glucan in native gels revealed a complete wipe out of one of the soluble starch synthases. Zymograms and kinetic analyses performed both in the mutant and in partially purified wild type extracts reveal at least two distinct activities that are partly analogous to higher plant soluble starch synthases I and II (SSI and II). The st-3 mutants were defective for SSII. Methylation and debranching of the purified amylopectin fraction clearly show a decrease in the number of intermediate size glucans (dp8 to 50) and an absolute and relative increase of very short glucans (dp2 to 7). These results suggest that a soluble starch synthase may be necessary for the synthesis or maintenance of intermediate size glucans that are the main component of the branched clusters of amylopectin. PMID- 8344908 TI - Isolation and characterization of proteolytic fragments of human factor VIIa which inhibit the tissue factor-enhanced amidolytic activity of factor VIIa. AB - The interaction of circulating factor VII/VIIa with tissue factor presented by cells in extravascular tissues represents the initial event in the extrinsic pathway of blood coagulation. To determine the tissue factor binding domains in human factor VIIa, we have subjected recombinant human factor VIIa to tryptic digestion and isolated two proteolytic fragments (molecular mass = 32 and 20 kDa) by a combination of immunoaffinity chromatography and reversed phase high performance liquid chromatography (HPLC) which strongly inhibits the tissue factor-enhanced amidolytic activity of factor VIIa and inhibits the activation of factor X by factor VIIa in the presence of tissue factor. The 32-kDa factor VIIa fragment consisted of residues 1-137/143 from the light chain of factor VIIa connected by a disulfide bond to residues 153-277 from the heavy chain. The 20 kDa factor VIIa fragment consisted of residues 1-137 of the light chain of factor VIIa in disulfide linkage with residues 248-266 of the heavy chain. The 32- and 20-kDa factor VIIa fragments inhibited the tissue factor apoprotein-enhanced factor VIIa amidolytic activity with Ki values of 35 and 65 nM, respectively. The Ki values for the inhibition of relipidated tissue factor apoprotein-enhanced factor VIIa amidolytic activity by the 32- and 20-kDa factor VIIa fragments were 70 and 610 nM, respectively. Factor X activation by factor VIIa-relipidated tissue factor was inhibited half-maximally by the 32- and 20-kDa factor VIIa fragments at 65 and 680 nM concentrations, respectively. Equilibrium binding studies indicated that the 32- and 20-kDa factor VIIa fragments interacted with cell surface tissue factor expressed on J82 cells in a specific and saturable manner with Kd values of 30 and 64 nM, respectively. In addition, a peptide consisting of residues 1-109 from the light chain of factor VIIa obtained by reduction and HPLC of the 20-kDa factor VIIa fragment retained inhibitory activity, but the selective removal of the gamma-carboxyglutamic acid domain from the 20-kDa factor VIIa fragment by cathepsin G cleavage resulted in the complete loss of inhibitory activity in this fragment. Our data strongly suggest that the epidermal growth factor-like domains covalently linked to the gamma carboxyglutamic acid domain in factor VIIa constitute the high affinity tissue factor binding domain in this molecule. PMID- 8344909 TI - Leucine/isoleucine/valine-binding protein contracts upon binding of ligand. AB - Small-angle x-ray scattering and computer modeling have been used to study the effects of ligand binding to the leucine/isoleucine/valine-binding protein, an initial component of the high-affinity active transport system for branched-chain aliphatic amino acids in Escherichia coli. Measurements were made with no ligand present and with either L-leucine or L-valine present. Upon binding of either leucine or valine, there is a decrease in the radius of gyration, from 23.2 +/- 0.2 to 22.2 +/- 0.2 A, and in the maximum particle dimension, from 82 +/- 3 to 73 +/- 3 A. The x-ray structure of the unbound form has been determined and gives a radius of gyration and a maximum dimension consistent with the values found for the solution structure in this study (Sack, J. S., Saper, M. A., and Quiocho, F. A. (1989) J. Mol. Biol. 206, 171-191). The reduction in the radius of gyration and maximum dimension upon ligand binding can be accounted for by a substrate induced cleft closure in a combined "hinge-twist" motion. Modeling of the substrate-bound state was done by comparison of this protein with another periplasmic binding protein (L-arabinose-binding protein), which possesses a similar two-lobe structure and for which the x-ray structure is known in its ligand-bound form. PMID- 8344910 TI - Novel, non-crinophagic, degradation of connecting peptide in transformed pancreatic beta cells. AB - Proinsulin is converted to equimolar amounts of insulin and connecting peptide (C peptide) in pancreatic beta cell secretory granules. The fate of C-peptide, which remains soluble in granules while insulin is crystallized, was studied in a rat insulinoma cell line (INS cells). A pulse-chase approach demonstrated that insulin to C-peptide ratios (I/CP) began to rise in INS cells as soon as conversion took place, reaching 2.2:1 at 6 h of chase, and 5.3:1 by 24 h. During the first 4 h of chase, this ratio was inverted in the medium under basal conditions, possibly reflecting preferential secretion of C-peptide via the post granular constitutive-like pathway. However, the amount of C-peptide secreted to the medium (1.4%/h) was trivial compared with the net loss of C-peptide from the INS cells, estimated to be approximately 33% during the 1st h. As no extracellular degradation of insulin or C-peptide was observed, the data show progressive, extensive intracellular degradation of C-peptide. Stimulation of INS granule exocytosis revealed that the I/CP ratio in secretory granules is representative of that of cell extracts, indicating that C-peptide, but not insulin, is lost from functionally competent granules with time. This particular degradative route for C-peptide is thus distinct from crinophagy (fusion of granules and lysosomes) and was found to be much more active in INS cells than in primary islet beta cells. PMID- 8344911 TI - A cardiac clathrin assembly protein forms a potassium channel in planar lipid bilayers. AB - A novel clathrin assembly protein (designated cardiac AP-3) has been isolated from dog heart which forms a K+ channel in planar lipid bilayers. AP-3 facilitated the in vitro formation of clathrin cages, which is diagnostic for clathrin assembly proteins. AP-3 consists mainly of 100-, 97-, and 55-kDa bands. A GTP-binding protein of approximately 25 kDa also co-purifies. The 100-kDa band was recognized by a monoclonal antibody to the gamma-adaptin of bovine brain clathrin assembly protein AP-1. A polyclonal antibody to the approximately 100 kDa doublet (alpha- and beta-adaptins) of bovine brain AP-2 did not cross-react with the purified protein. Western blot analysis of cardiac subcellular fractions showed that anti-AP-1 immunoreactivity was strongest in a sarcolemma-enriched fraction. Little immunoreactivity was detected in other cardiac subfractions, including sarcoplasmic reticulum, intercalated discs, and mitochondria. When reconstituted into planar lipid bilayers, AP-3 displays ion channel activity. Permeability ratios were PK/PCl approximately 16 and PK/PNa approximately 3, indicating a cation-selective channel somewhat selective for K+ versus Na+. The K+ channel displays several subconductance states (9 and 12 picosiemens in the main) and was blocked by CaCl2 (mM), inositol 1,3,4,5-tetrakisphosphate (20 microM), inositol 1,4,5-trisphosphate) (40 microM), and guanosine 5'-O-(3 thiotrisphosphate) (mM). Thus, the cardiac AP-3 appears to act as a K+ channel modulated by inositol polyphosphates and a small GTP-binding protein. PMID- 8344912 TI - Identification of the metal ligands and characterization of a putative zinc finger in methionyl-tRNA synthetase. AB - A truncated form of the methionyl-tRNA synthetase (delta MTS), which has been cloned, overproduced, and characterized, was used in an attempt to better understand the role of the enzyme-bound zinc in the amino-acylation process. Apo , Zn(2+)-, Co(2+)-, and 113Cd(2+)-substituted delta MTS proteins were prepared in vivo and purified to homogeneity. Apo-delta MTS was devoid of enzymatic activity in the aminoacylation of tRNA(fMet) and in the methionine-dependent ATP pyrophosphate exchange reactions. Kinetic constants in both the aminoacylation and ATP-pyrophosphate exchange reactions for the Co(2+)- and 113Cd(2+) substituted delta MTS proteins were found to be identical with those of the native Zn2+ protein. The low energy absorption spectrum of Co(2+)-substituted delta MTS resembles the d-d transition bands characteristic of tetrahedrally coordinated Co(2+)-substituted proteins. A strong S-->Co2+ charge transfer absorption at 350 nm was clearly evident having a molar absorptivity consistent with four thiolate ligands. The environment of the metal center was further probed by measuring the 113Cd chemical shift of 113Cd(2+)-substituted delta MTS. A single resonance at 759.6 ppm was observed. This chemical shift is consistent with Cd2+ coordinated to four thiolate ligands. The Escherichia coli methionyl tRNA synthetase contains a potential metal binding sequence Cys-X2-Cys-X9-Cys-X2 Cys in a connecting polypeptide within the nucleotide fold. Titration of a 21 amino acid peptide corresponding to this putative metal binding site, Cys145 Cys161, was shown to bind Co2+ with a Kd of 120 +/- 11 microM. These results demonstrate that the isolated zinc finger binding domain is capable of specifically forming a stoichiometric complex with the divalent cation. Taken together, our studies identify the 4 cysteine residues in the zinc finger-like domain as the metal binding ligands in the E. coli methionyl-tRNA synthetase. The role of the enzyme-bound metal appears to be structural and not directly involved in catalysis. PMID- 8344913 TI - Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha-thyroid hormone receptor gene, during adipocyte differentiation. AB - Rev-ErbA alpha (Rev-Erb) is a nuclear hormone receptor-related transcriptional activator that is encoded on the noncoding strand of the alpha-thyroid hormone receptor (TR) gene. The similarities between Rev-Erb and receptors for differentiating agents, as well as the abundance of Rev-Erb mRNA in fat, led us to study Rev-Erb gene expression during adipogenesis. Remarkably, Rev-Erb mRNA levels increased dramatically during the differentiation of 3T3-L1 cells into adipocytes. Rev-Erb was similarly induced in the related 3T3-F442A cell line but not in nondifferentiating 3T3-C2 cells. The time course of Rev-Erb induction was similar to that of C/EBP alpha, an important transcriptional regulator in adipocytes, and Rev-Erb mRNA was superinduced by cycloheximide. Nuclear run-on assays indicated that an increased rate of Rev-Erb mRNA synthesis accounted for the increased steady state mRNA levels; the half-life of Rev-Erb mRNA was indistinguishable in preadipocytes and adipocytes. Treatment of preadipocytes with retinoic acid inhibited adipocyte differentiation and also prevented Rev-Erb induction. Thus, there is a correlation between Rev-Erb gene expression and differentiation, and transcriptional regulation by Rev-Erb could play an important role in the generation and/or maintenance of the adipocyte phenotype. Interestingly, and possibly related to the overlap between the Rev-Erb gene and the exon specific for TR alpha 2, the induction of Rev-Erb was also associated with a 3-fold increase in the ratio of TR alpha 1 to TR alpha 2 mRNA levels, indicating that Rev-Erb expression has the potential to modulate adipocyte gene expression by multiple mechanisms. PMID- 8344914 TI - Thyroid hormone-induced gene expression program for amphibian tail resorption. AB - The changes in gene expression leading to tail resorption that are initiated by thyroid hormone (TH) were studied in Xenopus laevis. Four of the less than 10 genes that are down-regulated during this period have been isolated; their mRNAs decay with identical kinetics. Twenty of the approximately 35 genes that are up regulated in the first 48 h have been isolated. The up-regulated genes fall into two kinetic patterns. After a lag of several hours, the direct response genes (including thyroid hormone receptor beta) increase their mRNA level steadily for 24-48 h. The delayed genes respond mainly in the second 24 h after TH addition. The importance of these genes for tail resorption is supported by the fact that they are all regulated developmentally during normal metamorphosis in tail and respond to hormone induction when the tail becomes competent to respond to TH. The relatively simple gene expression program leading to tail resorption is contrasted with the complex and multiple periods of gene expression during limb development. The gene expression screen defines the tail resorption program and has isolated the majority of TH-regulated genes. PMID- 8344915 TI - Role of the alpha subunit cytoplasmic domain in regulation of adhesive activity mediated by the integrin VLA-2. AB - To investigate the role of the alpha subunit cytoplasmic domain in the regulation of VLA-2 functional activity, we expressed several chimeric and deleted forms of the alpha 2 subunit in two different human cell lines, K562 and RD. Each mutant construct formed surface VLA-2 heterodimers as efficiently as wild type alpha 2 subunit, except for a construct (X2CO1127) truncated just before the consensus GFFKR cytoplasmic domain motif, that was not expressed at the cell surface. Truncation of the alpha 2 cytoplasmic domain just after the GFFKR motif resulted in a complete loss of constitutive activity of VLA-2 in RD cells. If the integrin was already constitutively inactive, as in K562 cells, the cytoplasmic domain deletion had no effect. In both K562 and RD cells, cytoplasmic tail deletion eliminated up-regulation of adhesion in response to the phorbol ester, phorbol 12 myristate 13-acetate (PMA). In comparison, exchange of the alpha 2 cytoplasmic domain with the alpha 4 or alpha 5 cytoplasmic domains had no effect on constitutive activity (in RD cells), or on constitutive inactivity (in K562 cells) and did not eliminate PMA-stimulated activity (in K562 or RD cells). These results clearly demonstrate that the cytoplasmic domain of an alpha chain (not necessarily from alpha 2 itself) is required to maintain VLA-2 constitutive activity and to allow a responsiveness to PMA stimulation. In cases where VLA-2 was either constitutively inactive (as in K562 cells) or inactive due to cytoplasmic domain deletion (e.g. in RD cells), agents such as Mn2+ or the anti beta 1 monoclonal antibody TS2/16 caused a marked increase in adhesive function, thus proving that the integrins were not irreversibly inactive, and that cellular regulatory constraints could be bypassed by extracellular stimuli. PMID- 8344916 TI - Amino acid exchange and covalent modification by cysteine and glutathione explain isoforms of fatty acid-binding protein occurring in bovine liver. AB - A unique property of the liver-type member of the family of fatty acid-binding proteins is the heterogeneic pattern observed upon isolation, which can only partly be ascribed to the state of lipidation. Here we unraveled the structural basis of the heterogeneity of delipidated liver-type fatty acid-binding protein (L-FABP). Charge fractions of L-FABP focusing at pH 6.0 and at pH 7.0/7.1 were first isolated from bovine liver. Upon reduction, however, two distinct isoforms, namely pI 6.0 L-FABP and pI 7.0 L-FABP, were observed. From these isoforms peptides were generated enzymically and chemically by four independent methods. Peptides were separated by reverse phase high performance liquid chromatography and analyzed by Edman degradation and plasma desorption mass spectrometry. The complete amino acid sequences of the isoforms were established; they consist of 127 amino acids and each is N-terminally blocked with an acetyl group. The difference between pI 6.0 L-FABP and pI 7.0 L-FABP was attributed to an asparagine-aspartate exchange at position 105. When tryptic peptides of the pH 7.0/7.1 fraction were analyzed, discrepancies between sequence and mass data of the peptides containing at position 69 the sole cysteine of L-FABP led to the disclosure of a cysteinylation occurring at this position and giving rise to the slightly more basic pH 7.1 species. Moreover, chemical modification studies revealed that a part of the pH 6.0 fraction was pI 7.0 L-FABP that was glutathionylated at Cys69. Neither modification, however, prevented the binding of fatty acids. Together amino acid exchange and covalent modification of cysteine entirely explain the heterogeneity of L-FABP from bovine liver. PMID- 8344917 TI - Reciprocal effects of proline and glutamine on glycogenesis from glucose and ureagenesis in isolated, perfused rat livers. AB - L-Proline and L-glutamine were used to probe the inverse relationship between glycogenesis and ureagenesis in isolated, perfused livers from 48-h fasted rats. Both amino acids may provide nitrogen in the form of NH+4 for carbamyl-P synthesis. However, one molecule of glutamine may provide additionally for the synthesis of one molecule of the urea cycle substrate L-aspartate, but proline can provide for the synthesis of a molecule of NH+4 or one molecule of aspartate on an either/or basis only. In all perfusates, glucose was initially 30 mM (to favor phosphotransferase activity of glucose-6-phosphatase) and 0.5 mM 3 mercaptopicolinate was present (to inhibit glyconeogenesis from endogenous substrates, from the added amino acids, and via the indirect pathway). Glycogenesis from glucose, perfusate and hepatic urea formation, and levels of hepatic glucose-6-P, citrulline, PPi, and carbamyl-P were measured. The addition of glutamine to the perfusate markedly stimulated the urea cycle, but not glycogenesis. Hepatic urea level, perfusate urea concentration, and hepatic citrulline and PPi increased while carbamyl-P content decreased. In contrast, proline stimulated glycogenesis from glucose, but not ureagenesis. In the proline supplemented compared with glutamine group, hepatic glycogenesis and carbamyl-P content increased; hepatic glucose-6-P levels showed a tendency toward increase; and hepatic urea formation, hepatic citrulline, and PPi levels were decreased. These observations are interpreted to support an hepatic mechanism whereby the relative availability of carbamyl-P to the urea cycle and as a substrate for glucose phosphorylation via phosphotransferase activity of the glucose-6 phosphatase system preliminary to glycogenesis from glucose is a major metabolic determinant. PMID- 8344918 TI - Energy transduction between membranes. TonB, a cytoplasmic membrane protein, can be chemically cross-linked in vivo to the outer membrane receptor FepA. AB - TonB, a cytoplasmic membrane protein, couples cytoplasmic membrane protonmotive force to active transport across the outer membrane of Escherichia coli. In vivo cross-linking studies were initiated to analyze TonB interactions with other cell envelope proteins. Four TonB-specific cross-linked complexes were detected with apparent molecular masses of 195, 77, 59, and 43.5 kDa. The 195-kDa complex was shown to contain both TonB and FepA, the outer membrane receptor for the siderophore enterochelin. The 195-kDa complex is absent in strains missing either TonB or FepA and can be detected by either TonB-specific or FepA-specific monoclonal antibodies. This is the first direct in vivo evidence that TonB can span the periplasmic space to interact physically with outer membrane receptors. Consistent with that observation, the outer membrane protease OmpT was shown to play a role in TonB turnover, both in the presence and absence of ExbB results in the rapid degradation of TonB. The absence of OmpT could be used to stabilize TonB in an exbB::Tn10 strain such that steady state levels of TonB protein are identical to a wild-type strain. Under those conditions, the absence of ExbB results in greatly reduced TonB activity, indicating that ExbB plays a direct role in energy transduction and probably secondarily protects TonB protein from proteolysis. The 59-kDa complex was absent in an exbB::Tn10 strain, suggesting either that ExbB is in the complex with TonB or that ExbB is required to form the 59-kDa complex. A tolQ nonsense mutation had no effect on the cross-linking profile observed, confirming that its participation in TonB-dependent phenomena is minor and most likely the result of evolutionary cross-talk. PMID- 8344919 TI - Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C. AB - We have determined the structural organization of the human gene that encodes nuclear lamins A and C, intermediate filament proteins of the nuclear lamina. Sequencing and restriction mapping show that the coding region spans approximately 24 kilobases. The 5'-proximal promoter region contains several GC rich stretches, a CCAAT box, and a TATA-like element of sequence TATTA. The lamin A/C gene contains 12 exons. Alternative splicing within exon 10 gives rise to two different mRNAs that code for pre-lamin A and lamin C. Consequently, two proteins are generated, only one of which, pre-lamin A, can be modified by isoprenylation. The intron positions in the human lamin A/C gene are generally conserved in the previously characterized genes for Xenopus lamin LIII and mouse lamin B2, but different from those in a Drosophila lamin gene. In the regions coding for the central rod domains, the intron positions are also conserved when compared with the intron positions in the genes for most cytoplasmic intermediate filament proteins except those for nestin and neurofilaments. Analysis of the intron positions in these genes supports the hypothesis that the nuclear lamins and other intermediate filament proteins arose from a common ancestor. PMID- 8344920 TI - Sequencing of the amylopullulanase (apu) gene of Thermoanaerobacter ethanolicus 39E, and identification of the active site by site-directed mutagenesis. AB - The complete nucleotide sequence of the gene encoding the dual active amylopullulanase of Thermoanaerobacter ethanolicus 39E (formerly Clostridium thermohydrosulfuricum) was determined. The structural gene (apu) contained a single open reading frame 4443 base pairs in length, corresponding to 1481 amino acids, with an estimated molecular weight of 162,780. Analysis of the deduced sequence of apu with sequences of alpha-amylases and alpha-1,6 debranching enzymes enabled the identification of four conserved regions putatively involved in substrate binding and in catalysis. The conserved regions were localized within a 2.9-kilobase pair gene fragment, which encoded a M(r) 100,000 protein that maintained the dual activities and thermostability of the native enzyme. The catalytic residues of amylopullulanase were tentatively identified by using hydrophobic cluster analysis for comparison of amino acid sequences of amylopullulanase and other amylolytic enzymes. Asp597, Glu626, and Asp703 were individually modified to their respective amide form, or the alternate acid form, and in all cases both alpha-amylase and pullulanase activities were lost, suggesting the possible involvement of 3 residues in a catalytic triad, and the presence of a putative single catalytic site within the enzyme. These findings substantiate amylopullulanase as a new type of amylosaccharidase. PMID- 8344921 TI - Cholesterol ester transfer mediated by lipid transfer protein as influenced by changes in the charge characteristics of plasma lipoproteins. AB - The relationship between the cholesterol ester (CE) transfer activity of lipid transfer protein (LTP) and its affinity with lipid and lipoprotein particles was investigated. The study of the effects of chemical modification of low density lipoprotein (LDL) amino groups and carboxyl groups on the CE transfer activity showed that the maximal activity is obtained upon succinylation or acetylation of approximately 7% of LDL amino groups. Further increases in the extent of modification progressively reduced the transfer activity. The treatment of LDL with fatty acids gave results comparable to the chemical modification of LDL amino groups. The addition of low concentrations of fatty acids was stimulatory, while that of high concentrations was inhibitory. Although increases in the positive charges of LDL by the carboxyl group modification did not appreciably influence the CE transfer, the addition of cationic detergents gave a profound effect on the CE transfer. A maximal CE transfer activity was obtained upon addition of very small amounts of the detergents, with the higher concentrations sharply reducing the transfer activity. We also studied the effects of the concentrations of phosphate buffer and various salts on the CE transfer as well as the affinity of LTP for very low density lipoproteins, low density lipoproteins, high density lipoproteins 3, and high density lipoproteins 2. It appeared that the affinity of LTP for various lipoproteins is governed by a delicate balance of electrostatic and hydrophobic interactions. Optimal degrees of the interaction of LTP with both donor and acceptor particles seem to be required for the maximal degree of CE transfer. PMID- 8344922 TI - Structure, organization, and expression of the lct gene for lacticin 481, a novel lantibiotic produced by Lactococcus lactis. AB - The structural gene for the lactococcal lantibiotic lacticin 481 (lct) has been identified and cloned using a degenerated 20-mer DNA oligonucleotide based on the amino-terminal 7 amino acid residues of the purified protein. The transcription of the lct gene was analyzed, and its promoter was mapped. DNA sequence analysis of the lct gene revealed an open reading frame encoding a peptide of 51 amino acids. Comparison of its deduced amino acid sequence with the amino-terminal sequence and the amino acid composition of lacticin 481 indicates that the 51 residue peptide is prelacticin 481, containing a 27-residue carboxyl-terminal propeptide and a 24-residue amino-terminal leader peptide which lacks the properties of a typical signal sequence and which is significantly different from the leaders of other lantibiotics. The predicted amino acid sequence of prolacticin 481 contains 3 cysteines, 2 serines, and 2 threonines which were not detectable in amino acid analyses of mature lacticin 481. Based on these results and on characterization by two-dimensional NMR techniques, a structural model is proposed in which 2 cysteine residues are involved in lanthionine and one in beta methyllanthionine formation, and a 4th threonine residue is dehydrated. This model predicts a molecular mass for lacticin 481 of 2,901, which is in excellent agreement with that obtained from mass spectrometry. PMID- 8344923 TI - Thermodynamic and kinetic studies on the mechanism of binding of methylumbelliferyl galactosides to the basic agglutinin from winged bean (Psophocarpus tetragonolobus). AB - The binding of winged bean basic agglutinin (WBA I) to 4-methylumbelliferyl (MeUmb) galactosides was examined by extrinsic fluorescence titration and stopped flow spectrofluorimetry. Upon binding to WBA I, MeUmb alpha-galactosides show quenching in fluorescence intensity, decrease in UV absorbance with a concomitant blue shift, and decrease in fluorescence excited-state lifetimes. However, their beta-analogues show enhancement in fluorescence intensity, increase in UV absorbance with a red shift, and an increase in fluorescence excited-state lifetimes. This implies that the umbelliferyl groups of alpha- and beta galactosides experience non-polar and polar microenvironments, respectively, upon binding to WBA I. Replacement of the anomeric hydroxyl group of galactose by 4 methylumbelliferyl moiety increases the affinity of resulting saccharides. Substitution of C-2 hydroxyl of galactose by an acetamido group leads to increased affinity due to a favorable entropy change. This suggests that acetamido group of MeUmb-alpha/beta-GalNAc binds to a relatively non-polar subsite of WBA I. Most interestingly, this substitution also reduces the association rate constants dramatically. Inspection of the activation parameters reveals that the enthalpy of activation is the limiting factor for the differences in the forward rate constants for these saccharides and the entropic contribution to the activation energy is small. PMID- 8344924 TI - Structure-function relationships in an antifreeze polypeptide. The role of charged amino acids. AB - Several analogs of an alanine-rich alpha-helical antifreeze polypeptide were synthesized and studied to evaluate the role of charged amino acids on structure and activity. alpha-Helix content and thermal stability were assessed by circular dichroism spectrometry and antifreeze activity by freezing point depression (thermal hysteresis) and ice crystal growth rate measurements. Rearrangement, deletion and replacement of charged amino acids resulted in reduced helicity and antifreeze activity in some cases, but the effects were not dramatic. We conclude that the i+4 ion pair Lys18/Glu22 helps to stabilize the alpha-helix but is not absolutely essential for activity. NH2-terminal Asp does not contribute significantly to helix stability or activity, but the COOH terminus is sensitive to modification, since replacement of Arg37 can lead to reduced helix content and activity. In general, factors which reduce alpha-helix content also reduce antifreeze activity. PMID- 8344925 TI - Structure-function relationships in an antifreeze polypeptide. The effect of added bulky groups on activity. AB - We have proposed that the antifreeze activity of an alanine-rich alpha-helical antifreeze polypeptide (AFP) is due in part to side-by-side hydrophobic interactions of AFP molecules bound on the ice surface (Wen, D., and Laursen, R. A. (1992b) Biophys. J. 63, 1659-1662). To test this hypothesis and to assess the importance of a hydrophobic surface on the outward facing (non-ice-binding) portions of the helix, we synthesized several AFP analogs with up to four Ala- >Gln or Ala-->Leu replacements and determined the effect of these changes on antifreeze activity and helix stability. Although Gln replacements caused some helix destabilization and resultant reduction of antifreeze activity, they were in general well tolerated, suggesting that the bulk hydrophobicity of the non-ice binding faces of the AFP, per se, is probably not a major factor determining AFP activity. However, placement of either Gln or Leu in position 17 on one side of the helix completely abolished activity, demonstrating that the specific location of bulky groups can dramatically alter activity. We conclude from molecular modeling studies that the effect seen by placing bulky groups in position 17 is due to steric hindrance that prevents effective association or packing of AFP molecules on the ice surface, in support of our hypothesis. PMID- 8344926 TI - Molecular basis of the inhibition of beta s-chain-dependent polymerization by mouse alpha-chain. Semisynthesis of chimeras of human and mouse alpha-chains. AB - The transgenic mouse models expressing beta s-globin genes do not fully exhibit the sickling phenotype, primarily as a result of the inhibition of beta s-chain dependent polymerization by the mouse alpha-chains. The mouse alpha-chain differs from the human alpha-chain at 19 sequence locations. Of these, only alpha 78 and alpha 116 are the known hemoglobin (Hb) S polymer contact sites. To define whether the inhibition of polymerization by the mouse alpha-chain is solely a consequence of the differences at these two sites or additional sites of sequence differences are also involved, we have constructed chimeric alpha-chains by employing the alpha-globin semisynthetic reaction (Sahni, G., Cho, Y. J., Iyer, K. S., Khan, S. A., Seetharam, R., and Acharya, A. S. (1989) Biochemistry 28, 5456-5461). Mouse alpha 1-30 was spliced with human alpha 31-141 using endoproteinase Glu-C to generate a chimeric alpha-globin (alpha MH) containing eight of the 19 sequence differences of mouse alpha-globin. Similarly, human alpha 1-30 was spliced with mouse alpha 31-141 to generate another chimeric alpha globin (alpha HM) containing 11 sequence differences. The respective chimeric globins were purified, reconstituted with heme and beta s-chain into tetrameric hemoglobin, and the tetramers were purified by ion-exchange chromatography. The inhibitory potential of the chimeric alpha MH-chain on the polymerization is 10 fold lower than that of the mouse alpha-chain. The absence of the alpha 31-141 region of the mouse alpha-chain relieves only a portion of the inhibition. The inhibitory potential of alpha MH contributed by the mouse alpha 1-30 segment is significant although none of the sequence differences in this segment are located at any of the implicated polymer contact sites. The chimeric alpha HM-chain also inhibits the polymerization, but the extent of inhibition is again lower (4-fold) than that of the full-length mouse alpha-chain. The results demonstrate that the inhibitory potential of mouse alpha-chains involves the sequence differences from both the alpha 1-30 and alpha 31-141 regions. Besides, since the sum of the inhibitory potential of either of these chimeric alpha-chains is lower than that of the intact mouse alpha-chains, we speculate that conformational changes that require the copresence of sequence differences in both portions of the mouse alpha-chain also contribute to the inhibitory propensity of the mouse alpha chain. PMID- 8344927 TI - Effect of deletion from the carboxyl terminus of the 12 S subunit on activity of transcarboxylase. AB - Transcarboxylase from Propionibacterium shermanii is a biotin-containing enzyme which catalyzes the reversible transfer of a carboxyl group from methylmalonyl CoA to pyruvate. The central hexameric 12 S subunit of the enzyme associates with six 6 S subunits in the complete enzyme complex. We have constructed a series of cloned genes which encode COOH-terminal truncations of the 12 S subunit. Five of these subunits, which remained soluble following expression in Escherichia coli and were missing from 39 to 97 COOH-terminal amino acids, were purified and compared to the full-length subunit after enzyme complexes were assembled in vitro. All of the truncated subunits were 90% as active in the transcarboxylase reaction as wild type except the reaction containing the shortest complex, TC-12 S (1-507), which had 54% of the wild type activity (TC-12 S-WT). The reduced activity was not due to a lack of CoA ester binding sites or the Km for substrate. However, TC-12 S (1-507) was slower to form than TC-12 S-WT and had more incomplete complexes as judged by high performance liquid chromatography gel filtration profiles and electron microscopy. Isolated TC-12 S (1-507) was 70-80% as active as TC-12 S-WT. We also noted that the truncated form was heat-labile compared to wild type. We conclude that the COOH-terminal region of the 12 S subunit plays a role in assembly and stability of the hexamer and also affects the binding of 6 S subunits to form enzyme complexes. Once complexes do form, the catalytic capacity of TC-12 S (1-507) is almost the same as TC-12 S-WT. PMID- 8344928 TI - Stathmin gene family: phylogenetic conservation and developmental regulation in Xenopus. AB - The ubiquitous cytoplasmic phosphoprotein stathmin was proposed to play a general role as an intracellular relay integrating diverse signals regulating the proliferation, differentiation, and functions of cells (Sobel, A. (1991) Trends Biol. Sci. 16, 301-305). It was originally identified in mammalian cells and tissues, but antibodies directed against the mammalian protein also recognized a stathmin-like 19-kDa protein in all vertebrate classes. The immunoreactive protein in Xenopus laevis displayed, like mammalian stathmin, several nonphosphorylated and phosphorylated heat-soluble forms with distinct migration on two-dimensional polyacrylamide gel electrophoresis. Screening of Xenopus oocyte and brain cDNA libraries with a rat stathmin cDNA probe allowed us to isolate several stathmin-related cDNA clones, among which clone XO35 encodes the Xenopus homologue of stathmin whose deduced amino acid sequence is 79% identical to and displays most of the characteristic structural features of the mammalian protein. In particular, one of the cAMP-dependent protein kinase and the two "proline-directed" kinase-specific sites known to be phosphorylated in rat stathmin are also present in the Xenopus protein. Furthermore, two other sets of clones coding for related proteins belonging to the stathmin gene family were also isolated; clone SC15 encodes the Xenopus homologue of SCG10, a rat protein specifically related to neuronal differentiation; clone XB3 encodes a protein which, as SCG10 or SC15, possesses a stathmin-like domain and an additional N terminal extension but is more distant from SCG10 than SC15. Interestingly, the mRNA transcripts of Xenopus stathmin (XO35) appear ubiquitous, like stathmin in mammals, whereas the SC15 and XB3 mRNAs appeared as markers of the nervous tissue in Xenopus. During Xenopus oogenesis, stathmin accumulates and remains stable as a maternal product throughout early development. Concurrently, its phosphorylation is regulated from essentially unphosphorylated forms to highly phosphorylated ones in the mature egg, which are then progressively dephosphorylated again from the midblastula to the tailbud stage. Altogether, our results demonstrate the high evolutionary conservation of stathmin together with the members of its related gene family, not only at the level of their molecular structures, but also of their biochemical and biological regulation. These observations are thus further in favor of a very general and likely essential role of stathmin in the normal control of cells throughout development and in the adult. PMID- 8344929 TI - Photoaffinity labeling of human placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase with [alpha-32P]2N3NAD+. Identification of a peptide in the adenine ring binding domain. AB - Oxidation of many prostaglandins at C-15 results in the formation of 15-keto metabolites, which have reduced biological activity. This reaction is catalyzed by NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase. Using the photoaffinity analog of NAD+, [alpha-32P]nicotinamide-2-azidoadenine dinucleotide, we have identified a peptide in the adenine ring binding domain of the NAD+ binding site of 15-hydroxyprostaglandin dehydrogenase. The specificity of photolabeling was demonstrated by saturation and protection experiments. Saturation of photolabeling was observed at approximately 45-50 microM with an apparent Kd of 8-10 microM. Approximately 90% of photolabeling could be protected by 200 microM NAD+ when the protein was photolyzed in the presence of 10 microM probe. The photolabeled protein was digested with Staphylococcus aureus V8 or chymotrypsin, and the photolabeled peptides were purified by either boronate affinity chromatography or Fe+3 chelate chromatography followed by reverse phase HPLC. The photolabeled peptide region was identified to be Val32-Glu40. PMID- 8344930 TI - Arachidonate 12-lipoxygenase of platelet-type in human epidermal cells. AB - A homogenate of epidermal cells isolated from human skin converted arachidonic acid to 12S-hydroxy-5, 8,10,14-eicosatetraenoic acid and 15-hydroxy-5, 8,11,13 eicosatetraenoic acid as the main lipoxygenase products. The production of these hydroxy acids was not stimulated by the addition of 1 mM NADPH required for cytochrome P-450 reaction, but inhibited by 65-75% with 40 microM nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor. In addition to these lipoxygenase products, the epidermal cell homogenate converted arachidonic acid to prostaglandin E2 together with minor amounts of prostaglandins D2 and F2a and 12-hydroxy-5,8,10-heptadecatrienoic acid. Thromboxane B2 was not detected. This finding rules out the possible contamination of platelet 12-lipoxygenase in the epidermal cells. After subcellular fractionation of the epidermal cell homogenate, the 12-lipoxygenase activity was found in the 164,000 x g supernatant, the 164,000 x g pellet, and the 10,000 x g pellet. The cytosolic enzyme and the enzymes solubilized from the two pellets produced 12S-hydroperoxy 5,8,10,14-eicosatetraenoic acid as the primary product in contrast to cytochrome P-450 which produces primarily hydroxy acids. The 12-lipoxygenase in the 164,000 x g supernatant and the solubilized enzymes from the 164,000 x g pellet and 10,000 x g pellet were precipitable by antibodies raised against human platelet 12-lipoxygenase, but not by antibodies against porcine leukocyte 12-lipoxygenase. The immunoprecipitated 12-lipoxygenase from each fraction was almost inactive with linoleic acid as substrate, characteristic of 12-lipoxygenase of platelet type. Furthermore, 12-lipoxygenase mRNA in the epidermal cells could be reverse transcribed and amplified by polymerase chain reaction with the primers specific for human platelet 12-lipoxygenase cDNA, but not with those for porcine leukocyte 12-lipoxygenase cDNA. Thus, the 12-lipoxygenase of human epidermal cells is similar to human platelet 12-lipoxygenase in terms of immunogenicity, catalytic property, and primary structure, and distinct from leukocyte 12-lipoxygenase. PMID- 8344931 TI - Protein folding and assembly in vitro parallel intracellular folding and assembly. Catalysis of folding and assembly of the human chorionic gonadotropin alpha beta dimer by protein disulfide isomerase. AB - Although purified proteins will refold and assemble in vitro, it is not known if cellular factors change the mechanisms of these processes. Based on the gel migration of folding intermediates, the kinetic relationships between these intermediates, and on the order of formation of six disulfide bonds, we have found that the in vitro folding pathway of the human chorionic gonadotropin beta subunit (hCG-beta) is indistinguishable from the intracellular folding pathway. The same rate-limiting event was found in both folding environments; however, the t1/2 for this step in a cell is 4 min, whereas in vitro the t1/2 was > or = 80 min. Protein disulfide isomerase (PDI) increased the in vitro rate of this event (t1/2 = 25 min) without changing the order of disulfide bond formation. PDI also catalyzed the in vitro rate of assembly of hCG subunits. In intact cells, assembly of the alpha beta heterodimer occurs before all of the intramolecular disulfide bonds of beta are formed. In vitro, assembly was increased after reduction of two of the carboxyl-terminal disulfide bonds of hCG-beta by PDI. These results strongly suggest that both in intact cells and in vitro, partially unfolded hCG-beta is more assembly-competent than is fully folded hCG-beta. The comparison of in vitro and intracellular hCG-beta folding and hCG subunit assembly which is shown in this report indicates that the assisted folding and assembly pathway that occurs in cells, where proteins such as PDI play a role, differs only in rate but not in the order of disulfide bond formation or in the precursor-product relationships among the folding intermediates. PMID- 8344932 TI - Regulation of neutrophil elastase activity by elastin-derived peptide. AB - To understand the interaction between elastin and elastase, elastin from human aorta was incubated with human leukocyte elastase under conditions favoring proteolysis. Low molecular weight species were separated from the protein fraction by a small centrifuged gel filtration column. The only product of the elastin digest detected on acid polyacrylamide gel electrophoresis was a single band of slower cathodal mobility than human leukocyte elastase alone. This band cross-reacts with antibody to human elastase, indicating that the slow migrating band contains elastase. The putative human leukocyte elastase-elastin-derived peptide complex was treated with hydroxylamine to cleave any possible acyl-enzyme complexes and was then measured for amidolytic activity. Analysis of the amino acid composition of elastin-derived peptide indicates the presence of alanine, glycine, and richness in hydrophobic residues, suggesting that these residues are involved in elastase interaction(s). Incubation of the elastase-elastin-derived peptide with alpha 1-protease inhibitor causes dissociation of the complex and formation of an elastase-alpha 1-protease inhibitor complex. Our results suggest that, locally at the site of proteolysis, elastase activity may be regulated by elastin-derived peptide(s) during elastinolysis. PMID- 8344933 TI - HIV nucleocapsid protein. Expression in Escherichia coli, purification, and characterization. AB - The single-stranded nucleocapsid protein that coats the RNA genome of human immunodeficiency virus within the virion core has been produced in Escherichia coli and purified to homogeneity. The mature 55-amino acid protein, normally generated from the gag polyprotein precursor by HIV protease-catalyzed processing of both its amino and carboxyl termini, was produced in E. coli with authentic termini directly, without the need for processing. The protein was purified 30 fold to apparent homogeneity, as determined by both amino acid analysis and SDS polyacrylamide gel electrophoresis. Sequencing of each terminus of the purified protein indicated that no proteolytic degradation occurred. A molar extinction coefficient (epsilon 280 = 8350 cm-1 M-1) was determined. The purified nucleocapsid protein binds tightly to single-stranded RNA as judged by a nitrocellulose filter binding assay. A binding constant (Kw) of 1 x 10(8) M-1 was calculated. Using fluorescence quenching of nucleocapsid protein upon RNA binding as an assay, a binding site size of seven nucleotides was determined. These results contrast to a larger 15-nucleotide site measured by others for a larger form of nucleocapsid protein-containing sequences from its immature precursor. The possible relevance of these findings are discussed. PMID- 8344934 TI - A 72-kilodalton fyn-related polypeptide (p72fyn-R) binds to the antigen receptor/CD3 (TcR/CD3) complex. AB - Protein-tyrosine kinases play crucial roles in the activation and transformation of T lymphocytes. In this study, we have identified a variant of the fyn kinase at 70-72 kDa (termed p72fyn-R) that can preferentially associate with the TcR/CD3 complex in certain T cells. Phosphoamine acid analysis revealed that the CD3 associated p72fyn-R is labeled on both tyrosine and serine/threonine residues. TcR/CD3-associated p72fyn-R could be specifically reprecipitated using anti-fyn antisera to both the N and C terminus of p59fyn. In addition, two-dimensional phosphotryptic peptide map patterns of TcR/CD3-associated p72fyn and anti-fyn precipitable p72 were identical. By contrast, a comparison of p72fyn-R and p62fyn showed similarities and differences. p72fyn-R possesses a peptide corresponding to the autophosphorylation site that migrates in the same position as found for p59/62fyn. However, p72fyn-R possessed at least four novel phosphorylated sites labeled on serine and threonine residues that are absent in the p62fyn pattern. Phosphatase digestion experiments indicated that p72fyn-R is more resistant to dephosphorylation than p59/62fyn. Two-dimensional phosphotryptic analysis indicated that the novel serine/threonine phosphorylation sites were responsible for the resistance to phosphatase digestion. Although the exact nature of the relationship between p72fyn-R and p59/62fyn remains undetermined, these data indicate that TcR/CD3 may utilize novel variants of src-related kinases in the generation of signals which regulate T-cell growth. PMID- 8344935 TI - Isolation and characterization of a temperature-sensitive mutant of Salmonella typhimurium defective in prolipoprotein modification. AB - A temperature-sensitive (ts) mutant of Salmonella typhimurium that accumulated unmodified murein prolipoprotein at 42 degrees C but not at 30 degrees C was identified. In vivo and in vitro studies of the biosynthesis of Braun's lipoprotein revealed that this mutant (SE5221) was defective in the glyceryl modification of prolipoprotein. The ts mutation was mapped to 60.6 min of the S. typhimurium chromosome and was linked to argA and cysH. A clone with a 1.4 kilobase S. typhimurium DNA insert that complemented the ts mutation and restored the prolipoprotein modification activity both in vivo and in vitro was isolated. DNA sequencing of the complementing region revealed an open reading frame encoding a protein with 291 amino acids lacking NH2-terminal signal sequence. This open reading frame is immediately 5' to the thyA gene and is allelic to umpA of Escherichia coli. Wild-type strains harboring the cloned gene exhibited elevated levels of prolipoprotein modification activity. At the non-permissive temperature, the mutation affected both growth and viability, and the mutant cells exhibited anomalous cell morphology. The ts phenotype was suppressed by the introduction of a lpp::Tn10 mutation. These results suggest that the cloned gene encodes prolipoprotein glyceryl transferase (lgt), and in the wild-type background, this prolipoprotein modification enzyme is essential for the growth and viability of S. typhimurium. PMID- 8344936 TI - Characterization of a temperature-sensitive mutant of Salmonella typhimurium defective in apolipoprotein N-acyltransferase. AB - On screening 440 temperature-sensitive (ts) mutants of Salmonella typhimurium, a mutant strain SE5312 which accumulated apolipoprotein (ALP) at 42 degrees C was identified. In vitro assay of apolipoprotein N-acyltransferase activity indicated that the mutant cell envelope contained reduced activity as compared to the wild type strain. Transduction with a Mud-P22 mapping set placed the ts mutation to 14 17 min region of the S. typhimurium chromosome. P22 transduction using transposon insertions in this region revealed a linkage of the ts mutation to cobD (6%), nag (8%), and corC68 (99%). The ts phenotype was complemented by a 2.3-kilobase EcoRI subclone derived from lambda-phage 170 of Kohara's bank of Escherichia coli. Restriction enzyme analysis of the cloned DNA revealed that this 2.3-kilobase EcoRI fragment included the copper transport (cutE) gene in E. coli. The mutant strain SE5312 was copper-sensitive at 30 degrees C, and the complementing clone conferred copper resistance and restored the ALP N-acyltransferase activity in the mutant cell. Wild-type strain of S. typhimurium harboring this clone exhibited elevated levels of ALP N-acyltransferase activity. These results suggest that the cloned gene encodes the ALP N-acyltransferase. Upon shift to the non-permissive temperature, the viability of the mutant cells decreased, and the mutant cells assumed anomalous morphology. Temperature-resistant revertants could be readily isolated, and a subset of tr revertants contained no detectable lipoprotein. A lpp::Tn10 derivative of the mutant SE5312 was also temperature resistant. These observations suggest that ALP N-acyltransferase is essential for the growth and viability of S. typhimurium, and this requirement is decreased in the absence of major outer membrane lipoprotein. PMID- 8344937 TI - Epithelial glycoprotein-330 mediates endocytosis of plasminogen activator plasminogen activator inhibitor type-1 complexes. AB - Epithelial glycoprotein 330 (gp330) is structurally similar to the multifunctional alpha 2-macroglobulin receptor/low density lipoprotein receptor related protein (alpha 2MR/LRP), gp330 and alpha 2MR/LRP bind Ca2+ with high affinity, and both receptors bind and mediate endocytosis of alpha 2MR-associated protein (RAP). In the present report, we describe that affinity-purified gp330 from rabbit renal cortex binds plasminogen activator inhibitor type-1 (PAI-1) complexed with urokinase-type plasminogen activator (uPA). alpha 2M-methylamine, which binds with high affinity to alpha 2MR/LRP, did not bind to gp330. The apparent Kd for binding of uPA.PAI-1 complexes was about 0.8 nM at 4 degrees C. The binding was calcium-dependent and inhibited by recombinant RAP (rRAP) and tissue type plasminogen activator-PAI-1 complexes. Thin sections of rabbit renal proximal tubules bound 125I-labeled uPA.PAI-1 and rRAP in the apical part of proximal tubules corresponding to the localization of gp330. The binding of 125I uPA.PAI-1 complexes in tubules was abolished by excess unlabeled rRAP, and a rRAP inhibitable endocytosis and degradation of labeled uPA.PAI-1 complexes was demonstrated by perfusion of isolated rabbit proximal tubules. The results establish an endocytotic function of gp330 and suggest that gp330 is an important component of the fibrinolytic system in gp330-containing epithelial as found in, for example, kidney and lung. PMID- 8344938 TI - A kinase-related protein stabilizes unphosphorylated smooth muscle myosin minifilaments in the presence of ATP. AB - An apparent paradox in smooth muscle biology is the ability of unphosphorylated myosin to maintain a filamentous structure in the presence of ATP in vivo, whereas unphosphorylated myosin filaments are depolymerized in vitro in the presence of ATP. This suggests that additional uncharacterized factors are required for the stabilization of myosin filaments in the presence of ATP. We report here that an abundant smooth muscle protein forms sedimentable complexes with unphosphorylated smooth muscle myosin, partially reverses the depolymerizing effect of ATP on unphosphorylated myosin, and promotes the assembly of minifilaments as revealed by electron microscopy. This protein is called kinase related protein (KRP) because it is derived from a gene within the gene for myosin light chain kinase (MLCK) and has an amino acid sequence identical to the carboxyl-terminal domain of MLCK. Consistent with the results with purified KRP, deletion of the KRP domain within MLCK results in a diminished ability of MLCK to interact with unphosphorylated myosin. KRP binds to the heavy meromyosin fragment of myosin but not to myosin rod or fragments lacking the hinge region and light chains. Altogether, these results suggest that KRP may play a critical role in stabilizing unphosphorylated myosin filaments and that the KRP domain of MLCK may be important for subcellular targeting to filaments. PMID- 8344940 TI - The gene encoding IFP 53/tryptophanyl-tRNA synthetase is regulated by the gamma interferon activation factor. AB - We have obtained genomic DNA encoding the interferon-gamma (IFN-gamma)-inducible IFP 53/tryptophanyl-tRNA synthetase. Comparison with several different IFP 53 cDNA clones revealed a complex pattern of alternatively spliced 5'-untranslated regions. The interferon-responsive region within the IFP 53 promoter was found to contain a gamma-interferon activation site (GAS) but not the interferon stimulated response element and to bind the gamma-interferon activation factor (GAF). GAF.GAS complexes contained the IFN-regulated 91-kDa protein. Competition experiments defined the GAS boundaries and showed that GAF binding to the IFP 53 GAS could be prevented by an excess of the IFN-gamma response regions of several other IFN-gamma-inducible genes. We thus provide evidence for a central role of GAS.GAF in gene transcription mediated by IFN-gamma and suggest a consensus sequence defining more precisely the requirements for GAF binding to DNA. PMID- 8344939 TI - Mouse ethanol-inducible cytochrome P-450 (P450IIE1). Characterization of cDNA clones and testosterone induction in kidney tissue. AB - A mouse cDNA clone for the ethanol-inducible cytochrome P-450 (P450IIE1) was obtained by screening a liver cDNA library with an oligonucleotide representing a consensus sequence found in the orthologous rat, human, and rabbit sequences. The protein sequence deduced from the cDNA sequence had an identity of 93% to rat, 81% to rabbit, and 76% to human orthologous sequences. The highest levels of P450IIE1 mRNA were found in liver of both sexes, and male kidney. Developmentally, C57BL/6 female liver P450IIE1 mRNA was detectable 1 day postpartum and reached steady-state levels in animals approximately 16-20 days of age. Kidney and adrenal gland P450IIE1 mRNA was found to be induced 25-50-fold and 4-fold by testosterone treatment, respectively, and the level in both tissues reached maximum levels between 12 h and 2 days after treatment. Nuclear run-on experiments demonstrated that testosterone treatment for 24-48 h resulted in a slight transcriptional activation of the P450IIE1 gene in the kidney. However, the increase in transcription rate was far below the increase in mRNA level, suggesting that much of the induction occurs by posttranscriptional mechanisms. This process requires the androgen receptor since mutant Tfm mice lacking receptor are not inducible. PMID- 8344941 TI - Intracellular Ca2+ and the regulation of early response gene expression in HL-60 myeloid leukemia cells. AB - To gain direct insight into the action of the second messenger Ca2+ on transcriptional regulation, we have developed an intact cell model in which the intracellular free Ca2+ concentration ([Ca2+]i) can be measured, set, and varied at any level within the physiological range and in which the expression of early response genes is assayed in parallel. Using promyelocytic HL-60 cells, we have observed an exquisite sensitivity to Ca2+ of c-fos, c-jun, and zif268 mRNA accumulation, since early and maximal inductions were observed at 200-300 nM [Ca2+]i. At early times (10-20 min), the [Ca2+]i dose dependence of c-fos transcription and mRNA accumulation displayed a bell shape since c-fos expression was barely modified at high (700-1,250 nM) [Ca2+]i. The threshold [Ca2+]i concentration for prolonged (60 min) c-fos mRNA accumulation was greater than 200 nM. This indicates that the quantitative effects of Ca2+ on a given gene can vary markedly as a function of both the [Ca2+]i concentration and the duration of stimulation. Strikingly, a [Ca2+]i perturbation of only 1 min was sufficient for full induction of c-fos and zif268 transcripts. This demonstrates that a transient perturbation of [Ca2+]i has long term effects on gene expression. The half-life of c-fos mRNA (16 min) was unaltered by Ca2+. Nuclear run-on analysis of the distribution of RNA polymerase II along the c-fos locus indicated that Ca2+ promotes a small increase in transcriptional initiation and a pronounced relief of a block to transcriptional elongation beyond intron 1. The extreme sensitivity to [Ca2+]i, in terms of both the length of time and the dose of [Ca2+]i required for maximal gene induction, demonstrates that Ca2+ is a major physiological regulator of early response gene expression. In addition, the results indicate that a c-fos intragenic element is the main target of Ca(2+) regulated transcriptional activation. PMID- 8344942 TI - Processing of the beta-amyloid precursor. Multiple proteases generate and degrade potentially amyloidogenic fragments. AB - Proteolytic processing of the beta-amyloid precursor proteins (APP) is required for release of the beta/A4 protein and its deposition into the amyloid plaques characteristic of aging and Alzheimer's disease. We have examined the involvement of acidic intracellular compartments in APP processing in cultured human cells. The use of acidotropic agents and inhibitors to a specific class of lysosomal protease, coupled with metabolic labeling and immunoprecipitation, revealed that APP is degraded within an acidic compartment to produce at least 12 COOH-terminal fragments. Nine likely contain the entire beta/A4 domain and, therefore, are potentially amyloidogenic. Treatment with E64 or Z-Phe-Ala-CHN2 irreversibly blocked activities of the lysosomal cysteine proteases cathepsins B and L but did not inhibit the lysosomal aspartic protease cathepsin D and did not alter the production of potentially amyloidogenic fragments. Instead, the inhibitors prevented further degradation of the fragments. Thus, large numbers of potentially amyloidogenic fragments of APP are routinely generated in an acidic compartment by noncysteine proteases and then are eliminated within lysosomes by cysteine proteases. Immunoblot and immunohistochemical analyses confirmed that chronic cysteine protease inhibition leads to accumulation of potentially amyloidogenic APP fragments in lysosomes. The results provide further support for the hypothesis that an acidic compartment may be involved in amyloid formation and begin to define the proteolytic events that may be important for amyloidogenesis. PMID- 8344943 TI - Sequencing and cloning of human prolylcarboxypeptidase (angiotensinase C). Similarity to both serine carboxypeptidase and prolylendopeptidase families. AB - Prolylcarboxypeptidase, a lysosomal serine carboxypeptidase, cleaves COOH terminal amino acids linked to proline, as in angiotensin II and III and [des Arg9] bradykinin. About 25% of the enzyme protein was sequenced, and the complete sequence was deduced from its human kidney cDNA. The cDNA insert contained an open reading frame of 1488 base pairs coding for a protein of 496 residues. The authentic NH2-terminal sequence matched the deduced protein sequence starting with residue 46, suggesting the presence of both a signal and propeptide. The mature enzyme (451 residues) has a calculated M(r) = 51,043, whereas the M(r) of the purified glycoprotein is 58,000, indicating 12% carbohydrate. The overall sequence identity with serine peptidases is low (10-18%), but sequences around residues of the putative catalytic triad (Ser134, Asp333, His411) are similar (30 67%) to both the serine carboxypeptidases (e.g. deamidase or lysosomal protective protein, yeast carboxypeptidase Y, and KEX1 gene product) and the prolylendopeptidase family. Thus, prolylcarboxypeptidase links these two families, suggesting an evolutionary relationship. It is inhibited (Ki = 2.6 x 10(-7) M) by benzyloxycarbonyl-Pro-prolinal, a specific inhibitor of prolylendopeptidase, another angiotensin metabolizing enzyme. Prolylcarboxypeptidase contains serine or threonine residues repeated as the 26th residue 7 out of 9 times, with identical or similar amino acids in other positions in the repeats. The KEX1 gene product contains a similar motif, with serine or threonine as every 27th residue. The importance of prolylcarboxypeptidase is strongly suggested by its presence in various organs and cells and by the substrates it cleaves. PMID- 8344944 TI - Effects of substitutions of closely related amino acids at the contact surface in an antigen-antibody complex on thermodynamic parameters. AB - We constructed a library of 512 kinds of Fv fragment, derivatives of a monoclonal antibody, D1.3, specific for hen egg-white lysozyme, in which a total of nine of the original amino acids were replaced by closely related amino acids at positions in the complementarity-determining regions of the H chain. More than 80% of the clones in the library produced Fv fragments in Escherichia coli. Two wild-type and 13 mutant Fv fragments were prepared in large quantities and subjected to analysis by differential titration calorimetry. The association constants of the 15 Fv fragments with hen egg-white lysozyme were distributed between 0.12 x 10(7) and 1.59 x 10(8) M-1. The changes in delta H0 and -T delta S0 caused by one-point mutation at each position did not have intrinsic values for each change. The same changes at one position had different effects on KA, delta H0, and -T delta S0 when differences had been introduced in other regions. The delta(delta G0) caused by a single-point mutation ranged from -0.56 to 1.56 kcal/mol. By contrast, the delta(delta H0) and delta(-T delta S0) caused by a single-point mutation ranged from -3.5 to 3.4 and from -3.8 to 3.4 kcal/mol, respectively. When antibodies gain the binding energy contributed by the effects of enthalpy, they lose the binding energy contributed by the effects of entropy and vice versa. In general, changes in entropy compensate for changes in enthalpy. PMID- 8344945 TI - Cloning and expression of a novel phosphatidylethanolamine N-methyltransferase. A specific biochemical and cytological marker for a unique membrane fraction in rat liver. AB - Phosphatidylethanolamine N-methyltransferase catalyzes the synthesis of phosphatidylcholine from phosphatidylethanolamine and is most active in liver. A cDNA for this enzyme from a rat liver cDNA library has been cloned, sequenced, and expressed in COS-1 cells, McArdle-RH7777 rat hepatoma cells, and Sf9 insect cells. The expressed protein was capable of converting phosphatidylethanolamine into phosphatidylcholine in intact COS-1 cells, which normally have very low methyltransferase activity. The calculated molecular mass of the methyltransferase protein is 22.3 kDa, which is equivalent to that of the pure protein isolated from rat liver. Comparison of the sequence of the cloned rat liver methyltransferase with the yeast phosphatidylethanolamine methyltransferase PEM2 gene product revealed 44% identical amino acids and 68% similarity in the two predicted protein sequences. A polyclonal antibody was raised against a synthetic peptide corresponding to the carboxyl-terminal region of the enzyme and was affinity purified. The antibody recognized a single protein with a molecular mass of approximately 20 kDa when either rat liver proteins or proteins derived from the transfected COS-1 cells were electrophoresed on polyacrylamide gels containing sodium dodecyl sulfate. Surprisingly, the antibody exhibited no reactivity with endoplasmic reticulum proteins, even though the major phosphatidylethanolamine methyltransferase activity resides on this subcellular organelle. Instead, the antibody specifically recognized a protein in a unique subcellular membrane fraction purified from a crude mitochondrial preparation on a Percoll gradient. Immunocytochemical examination by electron microscopy showed positive labeling only in unique regions of the hepatocytes. The data suggest that this phosphatidylethanolamine methyltransferase is a specific marker for this unique membrane fraction. PMID- 8344946 TI - Glycosylation of mammalian neurofilaments. Localization of multiple O-linked N acetylglucosamine moieties on neurofilament polypeptides L and M. AB - Neurofilaments are neuronal intermediate filaments that play an important role in the growth and maintenance of large myelinated axons. Mammalian neurofilaments are composed of three polypeptide subunits, designed as NF-L, NF-M, and NF-H, all of which are phosphorylated. Here, we demonstrate by several criteria that neurofilament polypeptides are also modified by an abundant type of intracellular protein glycosylation in which single N-acetylglucosamine monosaccharides are O glycosidically (O-GlcNAc) linked to serine or threonine residues. In purified neurofilament proteins, the O-GlcNAc modifications occur at a stoichiometry of approximately 0.1 and 0.15 mol of GlcNAc/mol of NF-L and NF-M, respectively. The predominant sites of O-GlcNAc attachment on NF-L and NF-M are identified using proteolysis, purification of the glycopeptides, and subsequent analysis by automated gas-phase sequencing, manual Edman degradation, and laser desorption mass spectrometry. For NF-L, both major sites of glycosylation (Thr21 and Ser27) are located at the NH2-terminal head domain. For NF-M, one major site (Thr48) lies within the NH2-terminal head domain, whereas the other (Thr431) is located at the tail domain. Deletions encompassing these sites have been shown previously to have a dominant detrimental effect upon neurofilament assembly, raising questions about the specific function(s) of the saccharide moieties at these sites. Specific identification of these O-GlcNAc attachment sites has set the stage for more detailed mutagenic analysis of O-GlcNAc functions on neurofilaments. PMID- 8344947 TI - p72syk tyrosine kinase is activated by oxidizing conditions that induce lymphocyte tyrosine phosphorylation and Ca2+ signals. AB - We have used H2O2 as a pharmacologic agent to examine the effects of oxidizing conditions on lymphocyte signal pathways. Treatment of Ramos cells with 5-10 mM H2O2 gave rapid and strong tyrosine phosphorylation of multiple cellular proteins and activation of p72syk to levels equal to or greater than that observed upon surface Ig cross-linking. Strong Ca2+ signals that could be blocked by the tyrosine kinase inhibitor herbimycin A were also observed under these conditions. However, there was no increase in activity for the Src family kinases p56lck, p59fyn, or p56/p53lyn. Our findings that the p72syk tyrosine kinase responds to H2O2 treatment of cells suggest that this kinase is likely to contribute to cellular tyrosine phosphorylation and calcium signaling induced by oxidizing conditions. Furthermore, H2O2 may be useful as a pharmacologic agent to distinguish the effects of p72syk-related kinases from those of Src family kinases. PMID- 8344948 TI - Cyclosporine A inhibits the activity of a TATA box-binding protein that is required for transcription from the adenovirus major late promoter. AB - Nuclear extracts from P1798 lymphoma cells support transcription from the adenovirus major late promotor (AdMLP) and the human histone H4 promoter. Nuclear extracts prepared from P1798 cells treated with 1 microgram/ml cyclosporine A for 24 h fail to support transcription from AdMLP, whereas transcription from the histone H4 promoter is unimpaired. Both control and cyclosporine-treated extracts contain proteins that interact with synthetic deoxyoligonucleotides that correspond to the CAAT box, TATA box, and upstream stimulatory element of AdMLP. Cyclosporine had no discernible qualitative or quantitative effect upon such DNA protein interactions, as observed by gel mobility shift assays. Analysis of 5' deletion mutants of AdMLP indicates that deletion of sequences upstream of the TATA box reduces AdMLP transcription by only 50%. This observation suggests that cyclosporine A, which inhibits AdMLP transcription by > 90%, is unlikely to act through changes in the amount or activity of upstream activators such as upstream stimulatory factor- or CAAT box-binding proteins. On the other hand, deletion of TATA box sequences between -50 and -11 base pairs virtually eliminates transcription from AdMLP in vitro. A partially purified TFIID fraction was obtained from control P1798 nuclear extracts. The TFIID fraction reconstitutes transcription from AdMLP when added to extracts from cyclosporine A-treated cells. Recombinant TATA box-binding protein also reconstitutes transcription from AdMLP in cyclosporine A-treated extracts. These results are consistent with the hypothesis that cyclosporine A regulates the activity of a subset of general transcription factors which are required for initiation from some promoters (such as AdMLP) but not from others (such as histone H4). PMID- 8344949 TI - Enzymatic generation of the amino terminus of the beta-amyloid peptide. AB - The major pathological change in Alzheimer's disease is the deposition of 39-42 amino acid beta-amyloid peptide (BAP) in the brain. Since BAP begins at the aspartate residue (Asp1, or codon 672 of the amyloid precursor protein (APP)770 transcript), the ability of several proteases to cleave the peptide bond methionine-Asp1 (M/D) was evaluated by using peptides and recombinant APP molecules as substrates. Cathepsin G and chymotrypsin cleave the synthetic peptide HSEVKMDAEF at M/D under acidic conditions, whereas cleavage at lysine methionine (K/M) predominates when the pH is alkaline. Trypsin and cathepsins B, D, and L are unable to cleave the synthetic peptide at M/D. Peptide SEVNLDAEF, representing the mutation found in early onset Alzheimer's disease families from Sweden, is cleaved by cathepsin G and chymotrypsin at leucine-aspartate (L/D). Incubation of cathepsin G with soluble protease nexin-2 obtained from recombinant APP (APP-REP) derivatives resulted in proteolytic cleavage at or near the amino terminus of BAP. Cathepsin G-mediated cleavage was also observed in the domain representing the amino terminus of BAP when mature plasma membrane-associated APP REP molecules were used as substrates. Our results strongly suggest the involvement of a chymotrypsin-like serine protease in the generation of the amino terminus of BAP beginning at Asp1. PMID- 8344950 TI - Purification and characterization of a poly(dA-dT) lux-specific DNA-binding protein from Vibrio harveyi and identification as LuxR. AB - A lux-specific DNA-binding protein was purified to homogeneity from Vibrio harveyi by chromatography on DEAE-Sepharose, DNA-cellulose, Superose 12, and Mono Q. A single polypeptide of M(r) = 23,000 was found on SDS-polyacrylamide gel electrophoresis with an amino-terminal sequence corresponding to that predicted for luxR, a gene that causes a shift in the transcriptional start site from position -123 to -26 base pairs upstream of the initiation codon of luxC in the V. harveyi lux operon and is required for high expression of lux mRNA in recombinant Escherichia coli. Identification of the DNA-binding protein as LuxR was confirmed by showing its absence in V. harveyi luxR-mutants and its synthesis in recombinant E. coli containing V. harveyi luxR. The LuxR protein was shown to bind to two specific (A + T)-rich regions of DNA upstream of the V. harveyi luxC gene: region A, -290 to -253 base pairs, and region B, -170 to -116 base pairs. Synthetic poly(dA-dT) but not poly(dA)-poly(dT) competed with the lux DNA for binding to LuxR suggesting that this protein may be a novel poly(dA-dT)-binding protein in prokaryotes. The LuxR protein inhibited transcription from the -123 promoter in vitro; however, transcription from the -26 promoter was not reconstituted suggesting the possible requirement for other factors in lux gene regulation. LuxR shared sequence identity with two proteins linked to the regulation of enzymes involved in electron transport indicating that it may be a member of a family of regulators of metabolic functions responsible for diverting electrons from the respiratory chain. PMID- 8344951 TI - The role of conserved amino acids in substrate binding and discrimination by photolyase. AB - DNA photolyases catalyze the light-dependent repair of pyrimidine dimers in DNA. We have utilized chemical modification and site-directed mutagenesis to probe the interactions involved in substrate recognition by the yeast photolyase Phr1. Lys517 was protected from reductive methylation in the presence of substrate, but not in its absence, and the specific and nonspecific association constants for substrate binding by Phr1 (Lys517-->Ala) were decreased 10-fold. These results establish a role for Lys517 in substrate binding. Mutations at Arg507, Lys463, and Trp387 reduced both the overall affinity for substrate and substrate discrimination. Sites of altered interactions in ES complexes were identified by methylation and ethylation interference techniques. Interaction with the base immediately 3' to the dimer was altered in the Phr1(Lys517-->Ala). DNA complex, whereas interactions with the phosphate and base immediately 5' to the dimer were reduced when Phr1(Arg507-->Ala) bound substrate. Multiple interactions 5' and 3' to the dimer were perturbed in complexes containing Phr1(Trp387-->Ala) or Phr1(Lys463-->Ala). In addition the quantum yield for dimer photolysis by Phr1(Trp387-->Ala) was reduced 3-fold. The locations of these mutations establish that a portion of the DNA binding domain is comprised of residues in the highly conserved carboxyl-terminal half of the enzyme. PMID- 8344952 TI - Stereochemistry specifies the regiochemistry of phosphorylation in two cAMP dependent protein kinase substrates. AB - The substrate specificity of the cAMP-dependent protein kinase has been assessed with peptides bearing threoninol diastereomers. The threoninol residue contains both a primary alcohol and a secondary alcohol, either of which may serve as a site of phosphorylation. The enzyme-catalyzed phosphorylation of Gly-Arg-Thr-Gly Arg-Arg-Asn-(2R,3R)-threoninol furnishes a Km of 498 +/- 39 microM and a Vmax of 7.8 +/- 0.2 mumol/min-mg, whereas the phosphorylation of Gly-Arg-Thr-Gly-Arg-Arg Asn-(2S,3S)-threoninol provides a Km of 16.3 +/- 0.8 microM and a Vmax of 16.0 +/ 0.4 mumol/min-mg. Mass spectral analysis of the phosphopeptide reaction products revealed that each species is phosphorylated only once. 1H-coupled 31P NMR experiments unequivocally demonstrated that the (2R,3R)-isomer is specifically phosphorylated at the secondary alcohol, whereas the (2S,3S)-isomer is exclusively phosphorylated at the primary alcohol. This regiospecificity appears to be a consequence of the stereochemistry at C-2 in the threoninol residues. The structural attributes of the protein kinase that appear to be responsible for the observed differentiation between the C-2 stereoisomers is discussed. PMID- 8344953 TI - Biochemical characterization of human osteoclast integrins. Osteoclasts express alpha v beta 3, alpha 2 beta 1, and alpha v beta 1 integrins. AB - The study of osteoclast integrins has been previously hampered by the lack of a source of large numbers of purified osteoclasts. Osteoclastoma, a human giant cell tumor of bone, supplied a rich source of osteoclasts within a tissue containing many diverse cell types. Osteoclastoma integrin immunostaining confirmed the presence of the integrin alpha v beta 3 complex and the alpha 2 and beta 1 integrin subunits on osteoclasts. However, weak integrin expression, for example with alpha v beta 5, was difficult to interpret. Purification with magnetic beads coated with vitronectin receptor monoclonal antibody (13C2) enabled osteoclast membranes to be isolated with high purity and yield (57%) from osteoclastoma tissue. Positively (osteoclast-enriched) selected membranes were biochemically assessed for integrin expression by immunoprecipitation and visualization by non-radioactive enhanced chemiluminescence. alpha 1, alpha 4, alpha 6, alpha 8, alpha M, alpha X, gpIIb, beta 4, beta 6, and beta 8 integrin chains were undetectable at a sensitivity of 1 ng. alpha 3, alpha 5, alpha L, beta 2, and alpha v beta 5 were found in the negatively selected osteoclastoma tissue but not in the positively purified osteoclast membranes. The presence of alpha v beta 1 and alpha 2 beta 1 dimers was demonstrated biochemically on the immunoisolated osteoclast membranes. Osteoclast alpha v beta 3 isolation by Arg Gly-Asp (RGD) affinity chromatography for NH2-terminal amino acid sequencing confirmed that the osteoclast vitronectin receptor was identical to that previously characterized on other cell types. In situ hybridization using human alpha v riboprobes in osteoclasts from human and rodent bone further demonstrated the high level and specificity of expression of alpha v vitronectin receptor in osteoclasts. PMID- 8344954 TI - The hydrophobic domain of dolichyl-phosphate-mannose synthase is not essential for enzyme activity or growth in Saccharomyces cerevisiae. AB - Dolichyl-phosphate-mannose synthase is a membrane-bound enzyme of the endoplasmic reticulum that catalyzes the formation of dolichyl phosphate mannose from dolichyl phosphate and GDP-mannose. It is an essential enzyme for growth of Saccharomyces cerevisiae, and, like other enzymes that utilize some form of the lipid dolichol as substrate, dolichyl-phosphate-mannose synthase contains a putative "dolichol recognition sequence" in the predicted membrane-spanning domain. To investigate the importance of this sequence in particular and the hydrophobic region in general, a series of mutants of dolichyl-phosphate-mannose synthase were constructed that contained successive deletions or mutations of the hydrophobic region, and their in vivo functions and in vitro activities were examined. While all of the mutant proteins exhibited decreased transferase activities in vitro compared to the wild-type enzyme, the sequence was not essential for growth or for protein glycosylation in S. cerevisiae. Interestingly, although deletion of the entire hydrophobic region resulted in a soluble protein, mutant proteins containing 3 or 8 hydrophobic residues at the carboxyl terminus were still membrane-associated. These mutant proteins could be released from membranes by treatment with sodium carbonate, indicating peripheral associations. PMID- 8344955 TI - Influence of different signal peptides and prosequences on expression and secretion of human tissue plasminogen activator in the baculovirus system. AB - Foreign secretory pathway proteins are often produced in surprisingly low amounts in the baculovirus/insect cell expression system. One possible reason for this is that heterologous signal peptides might be inefficiently recognized by the insect cell protein translocation machinery. This idea was supported by a recent study showing that secretion of a plant protein in the baculovirus system was enhanced when its signal peptide was replaced with an insect-derived signal peptide (Tessier, D. C., Thomas, D. Y., Khouri, H. E., Laliberte, F., and Vernet, T. (1991) Gene (Amst.) 98, 177-183). We have extended these observations by measuring the effects of different signal peptide and signal peptide-prosequence combinations on baculovirus-mediated expression and secretion of human tissue plasminogen activator (t-PA). Replacement of the native prepropeptide with signal peptides from a lepidopteran insect secretory protein (cecropin B), a major baculovirus structural glycoprotein (64K), or an abundant, highly conserved lumenal protein of the rough endoplasmic reticulum (GRP78/BiP, a 78-kDa glucose regulated protein/immunoglobulin heavy chain-binding protein), had no significant effect on t-PA expression or secretion. The same results were obtained with the signal peptide from honeybee prepromellitin, which was able to enhance secretion of plant propapain (Tessier et al., 1991 (above)). Similar results were obtained when heterologous signal peptides were combined with the native prosequence or when the intact cecropin B preprosequence was used. Translational initiation at an upstream, in-frame ATT, which could functionally inactivate any signal peptide, did not explain the low efficiency of t-PA secretion. Finally, deletion of the native signal peptide, prosequence, or both, failed to increase t-PA production. These results showed that insect-derived signal peptides and/or prosequences cannot always enhance the expression and/or secretion of foreign secretory pathway proteins in the baculovirus system. They also suggested that the inability of insect cells to recognize the processing signals in human t-PA efficiently is probably not the major factor preventing its high level production in this system. PMID- 8344956 TI - Phi 29 DNA polymerase active site. The conserved amino acid motif "Kx3NSxYG" is involved in template-primer binding and dNTP selection. AB - phi 29 DNA polymerase shares with other alpha-like DNA polymerases several regions of amino acid similarity. Among them, the conserved region characterized by the amino acid motif "Kx3NSxYG" has been proposed to form part of the polymerization active site of alpha-like DNA polymerases. Mutants in phi 29 DNA polymerase residue Tyr390 of this conserved motif had been previously described to be affected in DNA-dependent dNTP binding. In this paper, the functional significance of this conserved motif is further studied by the analysis of mutants in conserved residues Asn387, Ser388, and Gly391. Residue Phe393 of phi 29 DNA polymerase has also been selected as target for site-directed mutagenesis because of its conservation within the group of alpha-like DNA polymerases from genomes that replicate by a protein-priming mechanism. Mutant N387Y was shown to be affected both in initiation and polymerization reactions, showing 3-fold higher Km value for dATP and more than 11-fold lower Vmax value than the wild type enzyme in the initiation reaction; moreover, it was affected in enzyme-DNA translocation. Mutant S388G retained initiation and polymerization activities; interestingly, this mutation significantly increased the efficiency of dNTP incorporation in non-templated reactions. Mutation Gly391 to Asp abolished template-primer binding as shown by gel retardation assays; this mutant was drastically affected in template-dependent dNTP incorporation both in initiation and polymerization reactions, but the efficiency of the non-templated phi 29 terminal protein-deoxynucleotidylation was higher than with the wild-type protein. Mutation Phe393 to Tyr severely decreased initial binding to template primer DNA molecules, resulting in a reduced activity in DNA primer-dependent polymerization reactions but not in phi 29 terminal protein-dependent ones. PMID- 8344957 TI - Activation of cytosolic phospholipase A2 by transforming growth factor-alpha in HEL-30 keratinocytes. AB - In the mouse keratinocyte line HEL-30 the epidermal mitogen transforming growth factor-alpha (TGF-alpha) stimulated the rapid release of arachidonic acid in a dose- and time-dependent manner. The liberation of arachidonic acid was due to the activation of a Ca(2+)-dependent cytosolic phospholipase A2 (cPLA2). The activation mechanism critically depended on a functionally active epidermal growth factor receptor tyrosine kinase and occurred independently of phospholipase C-mediated increases in cellular diacylglycerol and inositol 1,4,5 trisphosphate concentrations and protein kinase C activation. The activation included an increase in cytosolic PLA2 (cPLA2) activity and an association of the enzyme with the membrane fraction. Both activation steps apparently occurred in the presence of basal cytoplasmic Ca2+ concentrations. Moreover, cPLA2 or a closely associated protein was found to be phosphorylated on tyrosine upon TGF alpha challenge of the cells. The data suggest that tyrosine phosphorylation is involved in the TGF-alpha-induced activation of cPLA2. PMID- 8344958 TI - Characterization of DNA synthesis at a restrictive temperature in the temperature sensitive mutants, tsFT5 cells, that belong to the complementation group of ts85 cells containing a thermolabile ubiquitin-activating enzyme E1. Involvement of the ubiquitin-conjugating system in DNA replication. AB - A temperature-sensitive mutant defective in DNA replication, tsFT5, has been isolated from the mouse mammary carcinoma cell line FM3A. DNA synthesis in tsFT5 cells at a restrictive temperature (39 degrees C) has been characterized in detail. Incorporation of [3H]thymidine decreased rapidly after an increase in temperature to 39 degrees C and the incorporation was less than 20% and 10% of the initial level after 4 and 8 h, respectively. Analysis by DNA fiber autoradiography revealed that the initiation of DNA replication at the origin of the replicons was impaired in tsFT5 cells but that the DNA chain elongation rate of the mutant cells did not decrease at the nonpermissive temperature. tsFT5 cells were confirmed to belong to the complementation group which includes ts85 cells arrested mainly in the G2 phase at the nonpermissive temperature. It has been observed that the amount of ubiquintin-conjugated histone H2A (uH2A) in ts85 cells decreases at the nonpermissive temperature (Marunouchi, T., Yasuda, H., Matsumoto, Y., and Yamada, M. (1980) Biochem. Biophys. Res. Commun. 95, 126-131). The amount of uH2A in tsFT5 cells also decreased rapidly at 39 degrees C. This decrease occurred at the same time as or slightly preceding to reduction in DNA synthesis, and the reappearance of uH2A was followed by the restoration of DNA synthesis after the temperature was reduced. A similar temporal relationship between decrease in the amount of uH2A and reduction in DNA synthesis was observed in ts85 cells cultured at 39 degrees C. However, the rates of the decrease of uH2A and of the reduction in DNA synthesis in ts85 cells were slower than those observed in tsFT5 cells. A comparison of the thermolability of purified ubiquitin-activating enzyme E1s revealed that the E1 from ts85 cells had a thermolability intermediate between those of the E1 from tsFT5 cells and of the wild-type cells. A reduction in the phosphorylation of histone H1 was observed in tsFT5 cells cultured at 39 degrees C, but the reduction occurred several hours after the decrease in uH2A and the reduction in DNA synthesis. PMID- 8344959 TI - N-syndecan (syndecan 3) from neonatal rat brain binds basic fibroblast growth factor. AB - The cell surface proteoglycan N-syndecan (syndecan 3) was isolated from neonatal rat brain. Purified brain N-syndecan had biochemical properties very similar to N syndecan previously identified in Schwann cells: it contained mainly, if not exclusively, heparan sulfate glycosaminoglycan chains and had a core protein with an apparent molecular mass of 120 kDa by sodium dodecyl sulfate-gel electrophoresis. We examined the interactions between purified N-syndecan and extracellular ligands using a solid phase binding assay. It was found that among all proteins tested, including a variety growth factors and extracellular matrix molecules, only basic fibroblast growth factor (bFGF) exhibited significant N syndecan binding. N-syndecan binding to bFGF was saturable and exhibited a KD = 0.5 nM. Soluble bFGF effectively competed with immobilized bFGF for binding to N syndecan, indicating that these two proteins also interact in solution. Heparin and heparan sulfate, but not chondroitin sulfate, inhibited N-syndecan-bFGF binding. Isolated N-syndecan core protein did not exhibit significant binding to bFGF. Thus, the heparan sulfate chains of N-syndecan, rather than its core protein, appear to be responsible for binding to bFGF. Interestingly, acidic fibroblast growth factor, which is structurally similar to bFGF, did not exhibit significant N-syndecan binding. N-syndecan also did not bind to several other heparin-binding proteins used in this study, indicating a high degree of specificity for the N-syndecan-bFGF interaction. Both N-syndecan and bFGF are abundant in neonatal brain, suggesting that N-syndecan may function as a co receptor for bFGF during nerve tissue development. PMID- 8344960 TI - Cloning, sequencing, and mutation of thiol-specific antioxidant gene of Saccharomyces cerevisiae. AB - We have previously shown that the yeast Saccharomyces cerevisiae contains an antioxidant enzyme that can provide protection against a thiol-containing oxidation system but not against an oxidation system without thiol. This 25-kDa enzyme was thus named thiol-specific antioxidant (TSA). We have now isolated and sequenced a yeast genomic DNA fragment that encodes TSA. Comparison of the predicted amino acid sequence of TSA with those of conventional antioxidant enzymes, including catalases, peroxidases, and superoxide dismutases, revealed no sequence homology. The 195-amino acid TSA sequence contains 2 cysteine residues. Southern blot analysis of petite yeast DNA, studies with protein synthesis inhibitors, and protein immunoblot analyses of cytosolic and mitochondrial proteins suggest that TSA is a cytosolic protein encoded by nuclear DNA (chromosome XIII). The yeast TSA gene was selectively disrupted by homologous recombination. The haploid tsa mutant was viable under air, suggesting that TSA is not essential for cell viability. The growth rates of the tsa mutant and wild type strains were identical under anaerobic conditions. However, under aerobic conditions, especially in the presence of methyl viologen or a peroxide (t-butyl hydroperoxide or H2O2), the growth rate of the mutant was significantly less than that of wild-type cells. This result suggests that TSA is a physiologically important antioxidant. PMID- 8344962 TI - Orphan receptor HNF-4 and bZip protein C/EBP alpha bind to overlapping regions of the apolipoprotein B gene promoter and synergistically activate transcription. AB - As the sole protein component of low density lipoproteins, apolipoprotein B (apoB) plays an important role in cholesterol metabolism. Previously, we found that the proximal promoter region of apoB (-81 to -52 relative to the start site) played a critical role in hepatocyte-specific gene expression and that that region contained overlapping binding sites for nuclear factors AF-1 (-81 to -62) and C/EBP (-69 to -52) (Metzger, S., Leff, T., and Breslow, J. L. (1990) J. Biol. Chem. 265, 9978-9983). In this study, we show that HNF-4, a member of the steroid hormone receptor superfamily, binds the AF-1 site on the apoB promoter and through it activates transcription in transient transfection assays in both liver and non-liver cell lines, HepG2 and HeLa, respectively. Mutational analysis of the AF-1/HNF-4 binding site indicated a correlation of HNF-4 binding and transcriptional activity. In addition, transient co-transfection experiments with HNF-4 and C/EBP alpha expression vectors showed that the two factors can synergistically activate transcription to levels more than 3-fold above the sum of either factor alone. Finally, using gel retardation analysis we show that purified HNF-4 and C/EBP proteins can concurrently occupy their overlapping binding sites on the apoB promoter in vitro. However, since the same system showed a lack of cooperative binding, we argue that an alternative mechanism is responsible for the synergistic effect of HNF-4 and C/EBP alpha on apoB gene transcription. PMID- 8344961 TI - Human RNA helicase A is homologous to the maleless protein of Drosophila. AB - RNA helicase A is an abundant nuclear enzyme of HeLa cells that unwinds double stranded RNA in a 3' to 5'direction (Lee, C. G., and Hurwitz, J. (1992) J. Biol. Chem. 267, 4398-4407). A complementary DNA (cDNA) clone expressing RNA helicase A was isolated by screening a human cDNA library with polyclonal antibodies produced against the purified protein. The deduced amino acid sequence from this clone showed that RNA helicase A is a member of the DEAH family of proteins thought to be helicases. Sequence comparison among all known proteins of the DEAH family revealed that the highest homology was between RNA helicase A and the maleless protein (MLE) of Drosophila. There was 49% identity and 85% similarity throughout the overall primary sequences of both proteins, suggesting that RNA helicase A is the human counterpart of Drosophila MLE. Polyclonal antibodies against Drosophila MLE recognized RNA helicase A in crude nuclear extracts of HeLa cells as well as the purified protein. A recombinant RNA helicase A containing 6 histidine residues at the NH2 terminus was expressed in Sf9 cells using a baculovirus vector. The protein isolated from insect cells and the enzyme purified from HeLa cells exhibited identical RNA helicase and RNA-dependent ATPase activities. PMID- 8344963 TI - Partial assembly of the yeast vacuolar H(+)-ATPase in mutants lacking one subunit of the enzyme. AB - Partial assembly of the peripheral and integral membrane sectors of the yeast vacuolar H(+)-ATPase has been detected in mutants lacking one subunit of the enzyme. Assembled complexes of the vacuolar H(+)-ATPase could be immunoprecipitated from biosynthetically labeled wild-type cells using monoclonal antibodies specific for the 69- and 60-kDa subunits of the enzyme, and assembled membrane (V0) sectors could be immunoprecipitated using a monoclonal antibody against the 100-kDa subunits. Parallel immunoprecipitations from mutant cells lacking one subunit of the vacuolar H(+)-ATPase revealed different degrees of assembly depending on the subunit that was missing. Partially assembled complexes of the peripheral subunits could also be detected in a soluble, cytoplasmic fraction from wild-type and mutant cells following glycerol gradient fractionation. The results indicate that the peripheral (V1) sector and integral membrane (V0) sectors of the yeast vacuolar H(+)-ATPase can assemble independently. The 69-, 60-, and 27-kDa subunits all appear to be necessary for any assembly of the V1 sector to occur, but these subunits and the 32-kDa subunit can assemble into a complex in the absence of the 42-kDa peripheral subunit. The implications of the results for the structure and assembly of the yeast vacuolar H(+)-ATPase are discussed. PMID- 8344964 TI - Induction and nuclear accumulation of fos and jun proto-oncogenes in hypoxic cardiac myocytes. AB - Hypoxic and ischemic stresses cause a series of well documented changes in myocardial cells and tissues, including increased anaerobic glycolysis, loss of contractility, changes in lipid and fatty acid metabolism, and eventual irreversible membrane damage and cell death. In this article we describe changes in the expression and regulation of the proto-oncogenes fos and jun in cardiac myocytes exposed to severe hypoxia. The mRNAs encoding c-Fos, c-Jun, Jun-D, and Jun-B were induced within 1 h of exposure to hypoxia, increased 5-10-fold between 1 and 4 h and then declined. These inductions coincided with loss in myocyte contractility but occurred before there was irreversible cell damage or significant ATP loss. Immunostaining with anti-Fos and anti-Jun antibodies revealed the accumulation of these proteins in hypoxic cell nuclei. Pre-treatment of cells with protein kinase inhibitors significantly repressed the response at the mRNA level. We propose that hypoxic stress in these cells activates signal transduction pathways, possibly involving protein kinases, that result in the inductions of fos and jun gene families. Therefore AP1 may regulate myocardial adaptive responses to hypoxia in advance of energy depletion, cell damage, or reoxygenation. PMID- 8344965 TI - Normal insulin receptor substrate-1 phosphorylation in autophosphorylation defective truncated insulin receptor. Evidence that phosphorylation of substrates might be sufficient for certain biological effects evoked by insulin. AB - A mutant human insulin receptor that lacked the 82 amino acids of the COOH terminus of the beta-subunit (del82) was studied. Both the wild type insulin receptor (HIR) and the mutant receptor were expressed in Chinese hamster ovary (CHO) cells by stable transfection. Autophosphorylation and tyrosine kinase activities toward exogenous substrates of solubilized and partially purified del82 were severely impaired. When CHO cells transfected with del82 (CHO-del82) were stimulated with insulin, autophosphorylation was decreased to a great extent compared with cells expressing HIR (CHO-HIR). Nevertheless, tyrosine phosphorylation of an endogenous substrate, pp185, and insulin receptor substrate 1 (IRS-1) in CHO-del82 was comparable with that in CHO-HIR. Insulin-stimulated activation of phosphatidylinositol 3-kinase activity in CHO-del82 was also equivalent to that in CHO-HIR. Moreover, CHO-del82 exhibited the same insulin sensitivity as CHO-HIR with respect to 2-deoxyglucose uptake and thymidine incorporation into DNA. Insulin-induced internalization in CHO-del82 was decreased by 46% as compared with that in CHO-HIR. These data suggest that: 1) the COOH-terminal domain of the insulin receptor may play an inhibitory role in the phosphorylation of pp185 and IRS-1; and 2) phosphorylation of substrates such as pp185 and IRS-1, rather than autophosphorylation of the receptor per se, correlates better with certain biological effects that were mediated by insulin, suggesting that phosphorylation of the substrates might be sufficient for transducing signals downstream. PMID- 8344966 TI - Angiotensin II regulates insulin-like growth factor I gene expression in vascular smooth muscle cells. AB - The potent vasoconstrictor peptide angiotensin II (ang II) has been shown to promote growth of vascular smooth muscle cells (VSMC) in vitro and in vivo. We have previously demonstrated that VSMC synthesize insulin-like growth factor I (IGF I), an important autocrine/paracrine growth factor. Exposure of quiescent VSMC to ang II caused a marked increase in IGF I mRNA levels, peaking at 6 h (199 +/- 26% above control) and sustained for at least 24 h. This increase was completely inhibited by actinomycin D. Nuclear run-on assays indicated that ang II stimulated IGF I gene transcription 3.6-fold. Protein synthesis inhibition with cycloheximide increased basal IGF I mRNA levels but blocked ang II-induced IGF I expression. Immunoreactive IGF I levels in VSMC-conditioned medium were increased by 2.7-fold 24 h following ang II exposure. Measurements of [3H]thymidine incorporation showed that ang II caused a 117% increase in DNA synthesis at 24 h that was almost completely inhibited in the presence of an anti IGF I antibody. Thus, ang II regulates transcription of the IGF I gene in VSMC and IGF I is required for ang II-induced DNA synthesis. These findings suggest a potentially important role for IGF I as a mediator of the vascular growth responses induced by activation of the renin-angiotensin system in vivo. PMID- 8344967 TI - Long term follow-up of Mitroflow pericardial valve prostheses in the small aortic annulus. AB - Between January 1985 and April 1992 we implanted 477 Mitroflow pericardial bioprostheses in 476 patients in our clinic. All except one valve prostheses were implanted in the aortic position. There were 160 male and 316 female patients, with a mean age of 74.1 years (range 30-89 years). Combined cardiac procedures were performed concomitantly with aortic valve replacement in 45 patients (9.5%): coronary artery revascularisation (n = 38), endarterectomy of the internal carotid artery (n = 4) and multiple valve replacement (n = 3). The sizes of the implanted Mitroflow prostheses were 100% in 19 mm, 70% in 21 mm, 60% in 23 mm and 8% in more than 25 mm. The hospital mortality was 1.3% (n = 5). During the mean follow-up period of 47.6 months valve failure requiring reoperation occurred in 7 patients (1.2%). The actuarial freedom from tissue failure is 89.9 +/- 2.5% and the actuarial survival rate is 90.3 +/- 1.7% (27 deaths) at 7 years. These findings corroborate our policy to continue to implant a pericardial prosthesis in the aortic position, especially in elderly patients with a smaller aortic annulus. PMID- 8344968 TI - Doppler echocardiographic evaluation of the Omnicarbon cardiac valve prostheses. AB - Comprehensive 2 D/Doppler examination of 98 patients (mean age 56), implanted between September 1984 and February 1991, with normally functioning aortic (n = 49) and mitral (n = 49) Omnicarbon valves (OC) were analyzed in order to characterize the normal hemodynamic profiles of the OC valves. The mean time from implantation was 36.4 months (range 6 to 78). The following parameters were assessed (average of 5 measurements): peak transvalvular velocity (peak V), peak instantaneous gradient (peak G), mean transvalvular gradient (mean G), effective aortic valve area (ef Va), modified aortic valve area (m Va), aortic permeability index (PI), mitral valve area (Mit Va). Doppler data were correlated to prosthetic sizes (ranging from 21-29 mm for aortic OC and from 23-31 mm for mitral OC). The study establishes normal Doppler hemodynamics for each size (especially in aortic position) of OC valves and shows excellent performance. Significant correlations between peak G, mean G, Pl, and prosthetic aortic valve size (AS) were moderate. By contrast there were strong relationships between AS and ef Va (r = 0.56, p < 0.001) or mVa (r = 0.55, p < 0.001). These data should be helpful to identify OC prosthetic dysfunction. PMID- 8344969 TI - Criteria to select proper valve prosthesis for aortic valve replacement. Comparative assessment of various valve prostheses via continuous wave Doppler echocardiography. AB - Continuous wave Doppler echocardiography was used to measure pressure gradients (PG) across various aortic valve prostheses [St. Jude Medical (SJM) valve: 55 cases; Bjork-Shiley (B-S) valve: 18 cases; Lillehei-Kaster (L-K) valve: 25 cases; and Omniscience (O-S) valve: 49 cases]. Disc-opening angles of the L-K and O-S valves were measured via cineradiography. Pressure gradient across the SJM valve tended to be low. Increase in pressure gradients during exercise tended to be greater in the small valves. There was a significant correlation between the valve area index (VAI) and pressure gradients in the SJM valve (PG = 85.3-40.2 x VAI, r = -0.71, p < 0.005) and in the B-S valve (PG = 64.6-23.3 x VAI, r = -0.89, p < 0.025). To keep pressure gradients below 20 mmHg, SJM valve #23 and B-S valve #25 should be selected for patients with a body surface area of 1.3-1.7 m2. In the L-K and O-S valves, there was no significant correlation between VAI and PG, likely because the disc-opening angles of these valves were suboptimal--averaging 57 degrees in the L-K valve and 47 degrees in the O-S valve. None of the patients with SJM or B-S valves had pressure gradients of 50 mmHg or above. However, pressure gradients exceeded 50 mmHg in 7 cases with the L-K valve (28%) and 10 with the O-S valve (20%), suggesting the necessity of careful follow-up in patients with these prostheses. PMID- 8344970 TI - Detection of internal carotid artery stenosis. Comparison of 2D-MR angiography, duplex scanning, and arteriography. AB - The purpose of this study was to compare digital subtraction angiography (DSA) and duplex scanning with 2D-Magnetic Resonance Angiography (MRA) to evaluate the accuracy of MRA in determining carotid stenosis. All three methods were applied to 101 carotid arteries in 51 patients. Diameter stenosis of the internal carotid artery was categorized as follows: 0 to 39%, 40% to 59%, 60% to 94%, 95% to 99%, and occlusion (100%). All images were read in blind fashion by different physicians. DSA is still considered the "gold standard" investigation. In 78 arteries the degree of stenosis according to MRA correlated exactly with that of conventional angiography. In the remaining 23, carotid arteries MRA upgraded the stenosis in 13 and downgraded it in 8. The principal problem is the overestimation of the lesion, which was particularly revealing in lesions of more than 60%. Furthermore to date MRA is not able to evaluate the presence of ulceration. For this reason 2D-MRA alone is not a reliable method for evaluating the presence of carotid artery stenosis. PMID- 8344972 TI - Splanchnic artery aneurysms. AB - From 1970 to October 1991, 26 patients affected by splanchnic artery aneurysms were observed and treated at the Department of General and Cardiovascular Surgery, University of Milan, Italy. Three splanchnic artery aneurysms were operated on in emergency. Visceral artery aneurysms are often completely silent and are generally detected during diagnostic procedures performed in order to clarify some diagnostic questions. When symptomatic they present a characteristic clinical picture of the involved vascular district. Two patients affected by aneurysmal disease of the proper hepatic artery died after operation. All the other splanchnic aneurysms underwent a successful surgical procedure. This study is aimed at analyzing some characteristic clinical pictures, diagnostic methods, therapeutic procedures and postoperative results. PMID- 8344971 TI - Emergency myocardial revascularization for myocardial infarction evolving outside the hospital. A feasible option when thrombolysis and coronary angioplasty have failed. AB - Most reports on emergency coronary revascularization deal with failed percutaneous transluminal coronary angioplasty (PTCA) or refractory ischemia which developed after hospital admission. The objective of this study was to evaluate the feasibility and prognosis of emergency revascularization for acute myocardial infarction evolving outside the hospital. Between 1974 and 1992 54 cases were included in this study. The patients had both electrocardiographic and clinical evidence of ongoing ischemia. One or more infarct-related obstructed coronary arteries were documented by emergency angiography. Since 1981, the patients have been given urokinase, and, since 1986, they have undergone PTCA initially and, when reperfusion failed, revascularization was started. Overall in hospital mortality has been 11.1% (6/54). All other patients were discharged in satisfactory condition. Follow-up for periods of up to nearly twenty years has been uneventful with the exception of two late sudden deaths. The above results confirm that emergency coronary revascularization is a therapeutical option worth considering. PMID- 8344973 TI - Lower extremity revascularization. AB - Atherosclerotic occlusive disease of the lower extremity in patients exhibiting severe rest pain, ulceration, or tissue necrosis represents a serious threat to extremities. In the past two decades the surgical approach in the treatment of lower extremity ischemia has changed significantly due to better understanding of segmental disease and infrapopliteal disease. Also, better visualization of leg and foot arteries due to improved angiographic and surgical techniques aided by magnification have all significantly contributed to increased limb salvage. Vein, when available, is the ideal graft material both for supra and infrapopliteal reconstruction. Availability of vein as a conduit can be increased when ectopic veins such as cephalic etc., are used and also when short segments of veins are used with unconventional distal inflow sites such as SFA, distal deep femoral artery, and popliteal artery. However, when vein is unavailable, PTFE graft is a good option particularly in patients with life expectancy of less than three years. Better understanding of graft failure has lead to better graft surveillance with PVR, ABI and Duplex scanning. Timely intervention with either PTA or surgery has lead to better secondary patency of grafts. Veith et al. looked at amputation rates during the period of changing therapeutic approach and found both a decrease in primary and secondary amputation rate implying the effectiveness of an aggressive therapeutic approach. Not all aspects of lower extremity disease are understood. However, infrapopliteal disease has now been addressed and new, innovative therapeutic approaches have made significant advances in limb salvage. PMID- 8344974 TI - Changing trends in the outcome of urgent aneurysms surgery. A retrospective study on 170 patients treated in the years 1966-1990. AB - During the last 25 years 170 patients with ruptured aortic aneurysms were treated in our centre for vascular surgery with an overall mortality of 54%. We have subdivided these patients into three groups according to temporal factors: the 1st group includes 16 patients treated in the years 1966-1978; the 2nd group includes 93 patients treated from 1979 to 1987; the 3rd group includes patients from 1988 to 1990. In these years no selection of patients was made and everybody still alive was operated on. Starting from the second period, haemodynamical monitoring of the patients was performed with the adoption of the Swan-Ganz catheter in almost all cases. Mortality in the first period was 69%, in the second period 60% and in the third period 40%. There was no difference in the haemodynamical state in the three groups. The difference lies in the number of surgical interventions per year: 1.33 intervention per year in the first period; 11.625 interventions per year in the second period and 20 in the third. We conclude that an improvement in the survival rate of patients undergoing urgent aortic aneurysm repair is due to precise haemodynamical intraoperative monitoring and a well trained surgical team. PMID- 8344975 TI - Preoperative evaluation of inferior vena cava involvement secondary to malignant abdominal neoplasms. AB - The authors report their experience of different imaging techniques (US, CT, MRI, and cavography) used to evaluate inferior vena cava involvement due to abdominal malignant neoplasms. The study is a retrospective analysis of preoperative data on 15 patients of both sexes in comparison with intraoperative and/or pathological findings. All patients underwent ultrasonography, with good results in all the venous segments studied, as for the CT scan; the limitation of both techniques is the unsafe evaluation of venous wall involvement when the neoplastic tissue is confined inside the vessel. The results obtained using MRI seem to be very encouraging, but we only studied three cases with this technique, and so cannot assess the real value of the method. In nine patients we performed inferior cava phlebography: we believe this to be a very reliable exam to demonstrate vessel wall invasion, even if it is a very invasive procedure, its limits being the inability to observe proximal thrombotic extension when the vein is completely obstructed by the tumor. On the basis of their experience the authors suggest a multi-technique imaging diagnostic procedure for preoperative staging with a view to obtaining as much information as possible to correctly program surgical procedure. PMID- 8344976 TI - New-style Univent with a light source on the blocker. AB - The author has introduced a new-style "endotracheal tube with a movable blocker" which has a transillumination light source on the front-most portion of the blocker. This device may obviate the need for bronchoscopic guidance of the blocker. PMID- 8344977 TI - Unilateral upper extremity edema. A case report. AB - A case report of a 28-year-old Hispanic male with a 5-month history of left arm, face and supraclavicular edema is presented. Chest radiography revealed bilateral pleural effusions. Thoracentesis was negative for malignant cells. Left arm venogram demonstrated compression of the left subclavian vein and lymphangiogram was consistent with perilymphatic stasis. Computerized tomography and magnetic resonance imaging demonstrated a questionable mass in the left side of the neck. On exploration of the left supraclavicular fossa, a severely fibrotic thoracic duct was encountered as well as a prominent scalene lymph node. Pathological section revealed an adenocarcinoma in both specimens which was positive for keratin and carcinoembryonic antigen. Chemotherapy was begun, however, the patient died 3 months later secondary to a respiratory arrest. This presentation of an adenocarcinoma arising from an unknown gastrointestinal source is unusual. A search should be made to locate the primary site. Prognosis is unclear but presumed poor due to the rarity of this presentation. PMID- 8344978 TI - Percutaneous aspiration embolectomy. AB - Percutaneous aspiration thromboembolectomy (PAT) for management of a spontaneous arterial embolus, or following a complication of balloon angioplasty, was initially described in 1984. Instrument developments using a new clot aspiration system have facilitated this procedure. We report a case where PAT was successful in retrieving a spontaneous arterial embolus, and describe this new technique. We feel that PAT broadens the armamentarium of the vascular surgeon in the management of emboli to the distal circulation, where the results for operative embolectomy are frequently less than ideal. PMID- 8344979 TI - Tissue-type plasminogen activator (t-PA) lysis of aortic and mitral valve thrombosis. AB - Valve thrombosis is one of the most serious complications after prosthetic valve replacement. We report the use of tissue-type plasminogen activator (t-PA) in the treatment of a patient with thrombosed aortic and mitral valves. Thrombolysis resulted in immediate hemodynamic improvement and resolution of congestive heart failure, thereby avoiding surgical intervention. Based on our experience, thrombolysis with t-PA is an effective alternative in the treatment of thrombosed prosthetic valves. PMID- 8344980 TI - Creatine-kinase isoenzyme pattern in colonic infarction consequent to acute aortic dissection. A case report. AB - Bowel infarction can complicate acute aortic dissection (AAD); in that case early diagnosis, which decreases the high mortality, is often difficult. We report the case of one patient who underwent surgery for AAD and developed a colonic infarction, which was clinically manifest on the 4th postoperative day. However, bowel ischemia was suspected already 48 hours after surgery, on the basis of the suggestive CK pattern and the absence of myoglobin in plasma. Total CK activity reached the highest level only 48 hours after surgery (92,800 U/l); the peak was coincident with LDH, which increased proportionally less; CK-MM constituted 100% of total CK activity. The absence of myoglobin in plasma excluded the presence of rhabdomyolysis. We conclude that such laboratory findings suggest the occurrence of severe bowel ischemia. PMID- 8344981 TI - The reconstruction of major femoral vessels in a four-year-old girl wounded with shrapnel. AB - A four-year-old girl who sustained an explosive injury to the femoral artery and vein underwent vascular reconstruction. An allograft was used as a substitute conduit for both the artery and the vein. Eight months after reconstruction there was no pulse deficit and decrease in systolic blood pressure, nor were there any signs of venous obstruction. PMID- 8344982 TI - Type IV collagenase(s) and TIMPs modulate endothelial cell morphogenesis in vitro. AB - It has been proposed that proteases are important in endothelial cell behavior. We examined the contribution of the gelatinase/type IV collagenase system in an in vitro model of endothelial differentiation. Human umbilical vein endothelial cells rapidly align and form networks of tubes when cultured on a basement membrane preparation, Matrigel. Zymograms of culture supernates demonstrate a 72 kD and a 92-kD gelatinase activity; the cells produce most of the 72-kD gelatinase, whereas the 92-kD activity is derived entirely from the Matrigel. Addition of antibodies against type IV gelatinase/collagenase decreases the area of the tube network. Both tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, similarly decrease tube formation when added to cultures. Conversely, exogenous recombinant 72-kD gelatinase increases tube-forming activity. The effects of the anti-gelatinase antibodies and the TIMPs are not additive. Inhibition by either antibodies or TIMPs is greatest when they are added at culture initiation, suggesting that the protease activity is important in the early steps of morphogenesis. However, culture of the cells on Matrigel does not increase early expression of mRNA for the 72-kD gelatinase. Expression of message for the enzyme actually decreases during the course of the assay, while transcription of mRNAs for TIMPs increases, further supporting the concept that collagenases facilitate an early event in tube formation. These data demonstrate that gelatinase/type IV collagenase activity is important in endothelial cell morphogenesis on Matrigel, and suggest a role for collagenases in formation of new capillaries in vivo. PMID- 8344983 TI - Secretion of transforming growth factor-beta isoforms by embryonic stem cells: isoform and latency are dependent on direction of differentiation. AB - Murine embryonic stem (ES) cells are maintained in an undifferentiated state when cultured in medium conditioned by Buffalo rat liver (BRL) cells. BRL conditioned medium (CM) contains a differentiation inhibitory activity (DIA) that is synonymous with leukemia inhibitory factor (LIF). ES cells in monolayer culture can be induced to differentiate by addition of all-trans retinoic acid (RA) to the BRL CM, when they mainly form cells resembling parietal endoderm, or by culture in medium not conditioned by BRL cells. ES cells thus deprived of LIF/DIA differentiate spontaneously to a cell type that expresses Brachyury (T), a marker of early mesoderm. Northern blot analyses have shown previously that transcripts for transforming growth factor beta 1 (TGF-beta 1) are detected in undifferentiated cells while transcripts for TGF-beta 2 and TGF-beta 3 only become detectable after differentiation. We have now determined levels of TGF beta protein in CM and in the extracellular matrix (ECM) and have used neutralizing antibodies specific for TGF-beta 1 and TGF-beta 2 that do not react with recombinant human TGF-beta 3 to determine the isoform secreted. Using the growth inhibition of mink lung CCL64 cells as a bioassay for TGF-beta activity, we demonstrate that undifferentiated ES cells secrete latent TGF-beta 1 into the medium but no activity is found in their ECM. Cells induced to differentiate with RA contain TGF-beta 2 in both active and latent forms in their CM. Likewise their ECM contains TGF-beta 2 as the sole isoform. ES cells deprived of LIF/DIA secrete both TGF-beta 1 and TGF-beta 2 isoforms in their CM but TGF-beta-like activity remains after addition of neutralizing antibodies for TGF-beta 1 and TGF-beta 2. This active TGF beta is the major component of the TGF-beta activity in this CM. By contrast, ECM from LIF/DIA deprived cells contains only the TGF-beta 1 and beta 2 isoforms. The remaining activity in CM correlates with high expression of TGF-beta 3 by Northern blot analysis in these cells. We speculate that TGF-beta 3 is secreted by these cells and may be activated more efficiently and/or in a different manner to TGF-beta 1 and TGF-beta 2, since it is present in CM only in its active form. PMID- 8344985 TI - Transforming growth factor beta 1 selectively regulates ornithine decarboxylase gene expression in malignant H-ras transformed fibrosarcoma cell lines. AB - Negative growth regulators such as the transforming growth factor beta (TGF-beta) family appear to be important inhibitors in most tissue types. However, inhibition of DNA synthesis and cell proliferation is frequently lost during malignant transformation, and in some cases, tumor cell proliferation is actually stimulated by TGF-beta. The present study demonstrates a novel link between alterations in TGF-beta regulation during malignant conversion, and the expression of ornithine decarboxylase, a key rate-limiting activity in the biosynthesis of polyamines, and an enzyme that plays an important role in cell growth and differentiation. A panel of radiation and H-ras transformed mouse 10T1/2 cell lines exhibiting increasing malignant potential was investigated for possible TGF-beta 1 mediated changes in ornithine decarboxylase gene expression. Selective induction of gene expression was observed since only H-ras transformed cell lines with malignant potential exhibited marked elevations in ornithine decarboxylase message levels. Ornithine decarboxylase gene expression in nontransformed 10T1/2 cells and cell lines capable of only benign tumor formation was unaffected by TGF-beta 1 treatment. H-ras transformed cells were transfected with a plasmid placing the TGF-beta 1 coding region under the control of a zinc sensitive metallothionein promoter. When these cells were cultured in the presence of zinc an elevation of TGF-beta 1 mRNA was observed within 30 min. This increase in TGF-beta 1 message closely coincided with an elevation in ornithine decarboxylase message, and preceded an induction of jun-B, an early response gene in cells sensitive to TGF-beta 1 stimulation. Evidence for regulation of ornithine decarboxylase gene expression by TGF-beta 1 at both transcription and posttranscription was found. Actinomycin D pretreatment of malignant cells prior to TGF-beta 1 exposure prevented the increase in ornithine decarboxylase message. Marked differences in the rates of ornithine decarboxylase message decay were observed when cells treated with TGF-beta 1 were compared to untreated controls, with the half-life of ornithine decarboxylase mRNA increasing from 2.5 h in untreated cells to 17.5 h in cells exposed to TGF-beta 1. In addition, evidence was obtained for a cycloheximide sensitive regulator of ornithine decarboxylase gene expression, since the presence of this protein synthesis inhibitor increased the levels of ornithine decarboxylase message, and this effect was synergistically augmented by exposure of cells to cycloheximide and induction of TGF-beta 1 gene expression together.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8344984 TI - Modulation of myogenic determination factor 1 expression by cell-cell contact. AB - Myogenic determination factor 1 (MyoD1) expression is modulated by a variety of agents including growth factors and activated cellular proto-oncogenes. However, little is known about the effect of cell-cell contact, which increases as myoblasts terminally differentiate, on the control of MyoD1 expression. Steady state levels of MyoD1 transcripts decline over a 6-12 hour time period when myoblasts plated at a single cell density are incubated in media supplemented with 0.2% serum; by 48 hours MyoD1 mRNA levels have returned to the initial basal level. The decline in MyoD1 transcripts is diminished, but not prevented in myoblasts which maintain cell-cell contacts (at least 50% of cells with two or more sites of contact). MyoD1 transcript levels do not change if single cell cultures are maintained in 10% serum or are cocultured with fibroblasts. Analysis of conditioned media revealed that myoblasts plated at the single cell density or at a density which allowed multiple sites of cell-cell contact are not producing an activity(s) responsible for modulating MyoD1 mRNA levels. The changes in MyoD1 expression are mediated at the transcriptional level. Thus changes in the degree of cell-cell contact in cultures of myogenically determined cell lines effect changes in MyoD1 gene expression. Consequently when the influence of cytokines or other pharmacological agents on commitment to terminal myogenic differentiation is examined, the degree of cell-cell contact within the culture system may affect the response elicited. PMID- 8344986 TI - Transferrin is made and bound by photoreceptor cells. AB - Retinal pigment epithelial cells, which form one aspect of the blood-retinal barrier, control the access of blood-borne components such as diferric transferrin to the neural retina. It has recently been shown that RPE cells remove iron from diferric transferrin in a low pH compartment and subsequently release it in a low molecular weight form that can be chelated by apo-transferrin (Hunt and Davis: J. Cell Physiol. 152:102-110, 1992). It is now shown that photoreceptor cells can bind diferric transferrin to receptors on their inner segments. Moreover, polymerase chain reaction and in situ hybridization show that cells of the neural retina, particularly photoreceptors, make apo-transferrin. PMID- 8344988 TI - Microtubules are involved in transport of macromolecules by vesicles in cultured bovine aortic endothelial cells. AB - The macromolecular transport in bovine aortic endothelial monolayers, cultured in vitro, was studied by fluorescence microscopy, confocal laser scanning microscopy, and transmission electron microscopy. A fluid-phase endocytic tracer, fluorescein isothiocyanate dextran 70 kD (FITC-dextran 70), was found to be transported into and out of endothelial cells via vesicles arranged as chains stretching between the luminal surface and the cell interior and also from cell interior to the abluminal surface. The endocytic activity was reduced by colchicine, which disrupts microtubules, and increased during treatment with cytochalasin B, which blocks microfilament polymerization. These findings indicate that microtubules are required for fluid-phase endocytosis and that microfilaments hinder this process. PMID- 8344987 TI - Effect of pH and ATP on the equilibrium density of lysosomes. AB - Lysosomes are membrane bound structures that accumulate and hydrolyze material internalized by the endocytic pathway. A very conspicuous property of this subcellular compartment is its relatively high equilibrium density. The actual mechanism that regulates lysosomal density is poorly understood. In an attempt to gain knowledge on the factors that regulate lysosomal density we have assessed the equilibrium density of lysosomal markers after in vitro incubation of a lysosome-enriched subcellular fraction. Incubation at pH 6 for 10 min at 37 degrees C causes a density shift of several lysosomal markers to light density regions of Percoll gradients. Addition of ATP was able to prevent the acid induced density shift. Pretreatment of the vesicles with N-ethylmaleimide (NEM) or trypsin inhibited the effect of ATP. Working in intact cells, ATP depletion, a condition that causes cytoplasmic acidification, also decreases lysosomal density. The results indicate that at low pH lysosomal density is preserved by an active process that requires ATP and membrane associated proteins. PMID- 8344989 TI - Interaction of facilitative glucose transporter with glucokinase and its modulation by ADP and glucose-6-phosphate. AB - Bacterial glucokinase (GK) binds to purified, human erythrocyte glucose transporter (GT) reconstituted in vesicles. The binding is largely abolished if GT is predigested with trypsin, indicating that GK binds to the cytoplasmic domain of GT. The binding is a saturable function of GK concentration showing two distinct affinities with apparent KD of 0.33 and 5.1 microM. The binding is stimulated by an increasing concentration of ADP with the 50% maximal effect at 5 mM. Glucose-6-phosphate (G6P) also stimulates the binding with a distinct optimum at 25 mM. The binding is stimulated only slightly by ATP. D-glucose has no affect on the binding. KCl enhances the binding with the maximal effect at physiological intracellular concentrations. The binding is sensitive to changes in pH with an optimum at pH 4. The binding causes no detectable functional change in GT. However, the enzymatic activity of GK measured at nanomolar concentrations of GK is significantly greater in the presence of GT vesicles than in its absence or in the presence of protein-free vesicles, indicating that GK interacts with GT at this low concentration range with an apparent KD of 10 mM. Although its physiological significance is not known, the GK-GT interaction in vitro described here suggests that these two proteins may also interact in the cell and regulate carbohydrate metabolism. PMID- 8344990 TI - Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549. AB - Active oxygen species are generated in cells during pathophysiologic conditions such as inflammation and postischemic reperfusion. If oxygen radical scavengers are added before reperfusion, then the magnitude of injury is reduced. We investigated whether free radicals generated following exposure to hypoxia and reoxygenation activate voltage-dependent K+ ion channels in tumor cells in vitro. Using the technique of whole cell voltage clamping, we recorded currents from two families of potassium (K+) channels that were activated following reoxygenation. One of these groups possessed the electrophysical characteristics of a tetraethylammonium (TEA)-sensitive delayed rectifier channel and the other possessed characteristics of a Tea-insensitive slow inactivating channel. We present evidence which suggests that K+ channels are activated following reoxygenation but not during the hypoxia phase. The K+ currents decayed with time following reoxygenation. The decay characteristics of the K+ currents depended on the duration and level of hypoxia to which the cells were exposed. To determine whether activation of K+ channels by reoxygenation was initiated by free radicals, we pretreated cells with N-Acetyl L-Cysteine (NAC), a free radical scavenger, and found that this pretreatment abolished the currents induced by reoxygenation. We also present evidence that free radicals do not directly act on the channel itself, but activate a protein kinase which, in turn, activates the K+ channels. Taken together, these results indicate that one of the early responses to oxidative stress is the activation of K+ currents. PMID- 8344991 TI - Modulation of the immunophenotype of ovarian cancer cells by N,N dimethylformamide and transforming growth factor-beta 1. AB - Exposure of HOC-7 ovarian adenocarcinoma cells to regulators of cell differentiation caused inducer-dependent alterations of the antigenic pattern of the cells. Immunocytochemistry revealed that N,N-dimethylformamide (DMF) elevated the membrane staining for epidermal growth factor (EGF)-receptor and for desmoplakins I and II. DMF also stimulated cytoplasmic and surface labeling for CA 125 and the deposition of fibronectin into the extracellular matrix. Stimulation of fibronectin was also seen after addition of transforming growth factor (TGF)-beta 1. These responses were quantified using a fixed-cell, enzyme linked immunosorbent assay (ELISA) and revealed that DMF dose-dependently induced expression of EGF-receptor, CA 125, fibronectin, and desmoplakins I and II. TGF beta 1 stimulated fibronectin and desmoplakins I and II only. Production of EGF and TGF-alpha was not affected by these inducers. Immunocytochemistry, ELISA and Western blotting showed that both inducers caused down-regulation of myc oncoproteins. DMF was more effective in changing the immunophenotype of HOC-7 cells than TGF-beta 1. Desmoplakins I and II demonstrated elevated epithelial differentiation, whereas fibronectin indicated stimulation of extracellular matrix formation. Elevated EGF-receptor could not compensate for the growth inhibition induced by DMF. The expression of myc oncoproteins was inversely related to cell proliferation. CA 125, however, seems to be unrelated to cell growth. PMID- 8344992 TI - Estrogen enhances epidermal growth factor-induced DNA synthesis in mammary epithelial cells. AB - Estradiol (E2) priming (1 nM for 48 h) of normal murine mammary gland epithelial cells significantly increased the response of those cells to epidermal growth factor (EGF)-induced DNA synthesis. The synergism between E2 and EGF was evident in two aspects: After serum-free synchronization for 24 h, more cells entered the S-phase of the cell cycle after E2 priming and when treated with 0.17 nM EGF (13%) than did control cells (1.3%) or cells treated with EGF (4%) or E2 (3.5%) alone; further, the dose of EGF required to elicit maximal response was reduced an order of magnitude in estrogen-primed cells (0.17 nM) compared to controls (1.7 mM). Estrogen alone, however, did not increase DNA synthesis in these cells. Ligand binding studies indicate that these effects of estrogen on proliferating mammary epithelial cells may be explained, at least in part, by a 3.7-fold increase in the number of high affinity EGF-receptors observed in estrogen primed cells (7,300 receptors per cell) compared to estrogen deprived cells (1,960 receptors/cell). PMID- 8344993 TI - Intracellular calcium oscillations induced in a T-cell line by a weak 50 Hz magnetic field. AB - Applied weak magnetic fields have been shown to affect cellular activity on several levels, but the mechanisms involved remain elusive. We have decided to study an early signal transduction event in the human T cell line Jurkat; oscillations of free [Ca2+]i, of the type seen by crosslinking the CD3 complex. Cells were exposed to a 50 Hz, 0.1 mT, sinusoidal magnetic field while intracellular free calcium was measured in individual cells, using fura-2 as a probe. An acute response was observed with oscillatory increases in [Ca2+]i, which subsided when the field was turned off. The effect of the magnetic field on [Ca2+]i was comparable to that achieved by an anti-CD3 monoclonal antibody. PMID- 8344994 TI - Adhesion molecules in skeletogenesis: II. Neural cell adhesion molecules mediate precartilaginous mesenchymal condensations and enhance chondrogenesis. AB - Neural cell adhesion molecules (NCAM) was expressed transiently by mesenchymal cells in precartilaginous condensations of the embryonic chicken limb but was lost upon differentiation into cartilage. Consequently, NCAM was present in the periphery of the limb anlagen but was absent in the cartilaginous center of the growing limb. To determine NCAM function in limb bud chondrogenesis we incubated dissociated stage 22/23 distal mesenchymal limb bud cells with Fab' fragments of antibodies to NCAM. Cell aggregation was inhibited by incubating the cells with anti-NCAM Fab'. These results suggest that NCAM may mediate the formation of precartilaginous condensations. This hypothesis was further tested using micromass cultures. NCAM expression in micromass cultures in vitro recapitulated that in vivo. NCAM was enriched in condensations of 2 day cultures, but was diminished and concentrically distributed around cartilage nodules in 4 day cultures. Anti-NCAM Fab' fragments reduced the area occupied by precartilaginous condensations and the degree of chondrogenic differentiation. Control antibody against chicken embryo fibroblasts had no effect. The effect of overexpressing NCAM was analyzed by electroporating expression vectors directing the synthesis of chicken NCAM. Limb bud cells cultured after electroporation with an NCAM expression vector displayed larger cartilage nodules and greater chondrogenic differentiation than cells electroporated with vector alone. The expression of NCAM in electroporated cells also increased. Control experiments using plasmids encoding beta-galactosidase indicated that approximately 10% of the limb bud cells were transfected under these conditions. The results suggest that NCAM is involved in the chondrogenesis pathway by mediating the formation of precartilaginous condensations. PMID- 8344995 TI - Investigation of possible autocrine functions for rat GRO/CINC (cytokine-induced neutrophil chemoattractant). AB - Rat cytokine-induced neutrophil chemoattractant (CINC) is an eight kilodalton polypeptide originally purified from media conditioned by interleukin-1 beta stimulated 52E, an epithelioid clone derived from normal rat kidney (NRK) cells. Using a fibroblastic clone of the NRK cells, 49F, we found expression of the CINC gene to be induced by either serum or cytokines in growth-arrested cultures within 1 hour of stimulation. There was no observable CINC expression in exponentially growing cells in the absence of cytokine stimulation. CINC protein had no significant effect on 3H-thymidine incorporation or growth rate of NRK49F. We have observed that CINC is constitutively produced by some transformed NRK cells, clone RC20, suggesting an association with the expression of a transformed phenotype. Unlike the parent 49F, RC20 cells are capable of growth in soft agar and serum-free media and form highly metastatic tumors in nude mice. We have examined the possible autocrine functions of CINC and its possible links to the expression of the transformed phenotype by these cells. The use of a blocking CINC polyclonal antibody demonstrated that CINC did not function as an autocrine growth factor for RC20. Though CINC is a potent chemoattractant for neutrophils, it did not induce migration of either RC20 or 49F cells. CINC only moderately promoted adhesion of RC20 cells when used as a matrix protein. These data do not support the hypothesis that production of CINC by the RC20 cells provides an obvious advantage for the transformed cells constitutively producing it. PMID- 8344996 TI - High-level expression of cytokine-induced neutrophil chemoattractant (CINC) by a metastatic rat cell line: purification and production of blocking antibodies. AB - Significant levels of cytokine-induced neutrophil chemoattractant (CINC) were found in serum-free medium conditioned by a highly metastatic rat cell line, RC20. To study CINC's role in inflammation and metastasis, CINC was purified from this source for use in in vitro assays and for antibody production in goats and rabbits. CINC was a potent chemoattractant for rat neutrophils (EC-50 0.5 nM). A fusion protein of glutathione-S-transferase and CINC (GST-CINC) was produced in E. coli. Anti-CINC polyclonal IgG was purified from immune goat and rabbit sera by protein A and GST-CINC affinity chromatography. Both goat and rabbit anti-CINC antibody preparations at 4 micrograms/mL (an 11-fold molar excess) were found to completely block the activity of 2.5 nM CINC in a rat neutrophil chemotaxis assay. These antibodies have been used to develop a sensitive immunoassay for CINC. The availability of large amounts of affinity-purified blocking anti-CINC antibody will allow investigations into the role played by CINC in rodent inflammation models and in the metastasis of RC20 cells. PMID- 8344998 TI - Pharmaceutical care: desiderata. PMID- 8344997 TI - Deposition of reactive oxygen metabolites onto and within living tumor cells during neutrophil-mediated antibody-dependent cellular cytotoxicity. AB - In this study we test the hypothesis that reactive oxygen metabolites are delivered from neutrophils to simultaneously both the cell surface and cytosol of opsonized YAC erythroleukemic target cells. Using 5' (or 6') carboxyl-2',7' dichlorodihydrofluorescein (H2-CDCF) diacetate as starting material, we synthesized its succinimidyl ester derivative. H2-CDCF-conjugated IgG prepared from the succinimidyl ester derivative was used to opsonize targets. In vitro studies have shown that H2-CDCF becomes fluorescent upon exposure to reactive oxygen metabolites, including hydrogen peroxide. Using video intensified epifluorescence microscopy, we observed that reactive oxygen metabolites are deposited on tumor cell membranes during neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC). This deposition process is catalase sensitive. The role of reactive oxygen metabolites produced by neutrophils in triggering the oxidation of H2-CDCF is further supported by the observation that neutrophils from chronic granulomatous disease (CGD) patients did not affect target fluorescence. YAC tumor cells were also labeled with dihydrorhodamine 123 or dihydrotetramethylrosamine. The oxidized forms of these reagents were found within the cytoplasm of YAC cells. During ADCC normal neutrophils, but not neutrophils obtained from CGD patients, triggered the oxidation of dihydrorhodamine 123 and dihydrotetramethylrosamine within tumor cells. Using two color automated epifluorescence microscopy, we could not detect temporal intermediates with fluorescence in only one compartment, i.e., either solely on the plasma membrane or in the cytoplasm. These observations suggest that reactive oxygen metabolites cross target membranes (< 12 sec. These studies show that reactive oxygen metabolites are deposited both onto and into tumor cells during ADCC, wherein both compartments could become vulnerable to oxidant-mediated damage. PMID- 8344999 TI - Amphotericin B and its delivery by liposomal and lipid formulations. AB - In recent years, new formulations of the original amphotericin B preparation (Fungizone) have been devised in order to overcome toxicity problems that frequently occur. These preparations represent an improved method of drug delivery, with an increased therapeutic index and a decrease in toxicity to mammalian cell membranes. The new formulations have different physico-chemical characteristics and differ in pharmacokinetic parameters. Their effects must be compared with conventional amphotericin B to ascertain potential roles in future antifungal therapy. PMID- 8345000 TI - Serum creatinine levels during cardiac surgery: absence of effect by aminoglycosides. AB - The literature indicates that the relative nephrotoxicities of the three drugs used in this investigation are gentamicin > tobramycin > or = netilmicin. Serum creatinine levels over time were used in an attempt to elucidate the situation. They varied widely in all three groups and in controls in theatre. No definite trend was shown. Measurements performed for the ICU period showed continued variation. Fluctuations were so great during the perioperative period that the levels were analysed in terms of 44 mumol/litre difference between admission and discharge, ignoring changes between these times. It is now clear that the operative procedure itself is associated with fluctuating serum creatinine levels. The use of these aminoglycosides does not measureably affect the situation adversely over the short period of treatment. The use of nomograms, based on creatinine levels, to set aminoglycoside doses during the perioperative period may therefore be misleading, because of the wide fluctuations shown. PMID- 8345001 TI - Pharmacokinetics of fusidic acid after a single dose of a new paediatric suspension. AB - The pharmacokinetics of fusidic acid (Fucidine, Leo Laboratories) were studied in 10 children after single oral dosing with 20 mg/kg of a new banana-flavoured paediatric suspension (titrating at 50 mg/ml). Nine blood samples were drawn from each child at 0, 1, 2, 3, 6, 8, 12, 24 and 48 h following dosing with the antibiotic. Serum fusidic acid levels were measured by high-performance liquid chromatography (HPLC). A model-independent method was used for the pharmacokinetic analysis. Results were compared with those obtained after dosing eight healthy adult volunteers with 500 mg of sodium fusidate by parenteral administration (infusion) then per os. The acceptability of the single dose was good. The terminal elimination half-life t1/2 (h) and the mean residence time (MRT, h) of fusidate were similar to those determined in healthy adults after oral dosing, i.e. 16.0 +/- 14.5 versus 16.0 +/- 3.5 and 17.7 +/- 12.1 versus 17.7 +/- 2.5, respectively. In contrast, the oral bioavailability of the suspension (Fapprox., %) was relatively low: of the order of 22.5 versus 91.0% for tablets in the healthy adult, which justifies the use of a relatively higher dose in the child. This led to the calculation of an estimated total clearance (Clest., ml/min) significantly less than that in the healthy adults, while the estimated apparent volume of distribution (Vd, litre/kg) was significantly increased (10.4 +/- 9.1 versus 21.8 +/- 2.1 and 0.73 +/- 0.53 versus 0.30 +/- 0.04, respectively). Fusidic acid is normally excreted in metabolized form (98%). The decrease in clearance could be attributed to the almost immediate saturation of liver enzymes in immature infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345002 TI - Is there a need for improved pharmacy services to the operating theatre? AB - A study to assess the control and handling of drugs within an operating theatre complex (10 theatres) of an 850-bed hospital, has revealed the presence of unusable medication and thus highlighted the need for improved pharmacy services. The aims and objectives of the pharmacy department to enhance such services included improvement of drug control of stock medication and the introduction of clinical pharmacy services within the operating theatre. To undertake this, three systems were evaluated with reference to systems already in use in the U.S.A. Operating theatre visits by a clinical pharmacist, coupled with the expansion of the existing drug distribution service, were identified as the most cost effective methods that would allow the objectives to be met. Consequently, this has now been implemented within the operating theatre complex. PMID- 8345003 TI - The use of evaporative cooling to extend the shelf life of reconstituted oral penicillin solutions. AB - The relationship between temperature and the degradation of reconstituted penicillin solutions was evaluated. In all cases storage at temperatures of 25 degrees C or less was sufficient to maintain penicillin stability within acceptable pharmacopoeial limits for 5 days. In addition, the relationship between humidity and dry bulb temperature was examined in order to assess the use of evaporative cooling in lowering the temperature of penicillin solutions in those areas of the country where temperatures commonly exceed 25 degrees C. The results of this study suggest that, with the use of evaporative cooling, penicillin solutions can be maintained in a stable state for a 5-day period without the need for refrigeration. PMID- 8345004 TI - Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications. AB - The aim of the study was to characterize, from the relationship between total and free serum levels of valproic acid obtained over a broad dosage range (10-50 mg/kg), the parameters defining the in-vivo kinetic behaviour of the binding of valproic acid to plasma proteins, their pharmacokinetic and clinical repercussions, and their application to therapeutic drug monitoring (TDM). The study was performed in nine healthy adults (20-35 years) who were given doses of 1000 (group A), 2000 (group B) and 3000 mg (group C) of sodium valproate according to a compensated cross-over design, simultaneously determining the total and free serum levels of valproic acid over a 24-h period. The mean free fraction increases with dose, although this increase is only significant (P < 0.05) for the highest dose (3000 mg). The variation in the free fraction of valproic acid begins to become significant (P < 0.05) at a total drug concentration above 100 mg/l. The mean values of the dissociation constant (K) and binding sites (n) were 460 mumol/l and 1.79, respectively, showing a variability of 86.6 and 38.7%, respectively, and a residual variability of 13.0%. Significant differences (P < 0.05) were found for the total plasma clearance (Cl) but not for the intrinsic plasma clearance (Clu) values, despite their tendency to decrease with the dose. If TDM is to be used for valproic acid, it is the free serum levels that should be determined, especially if high doses are administered, because the total serum levels are not a true reflection of the free ones, as is the case of other anti-epileptic drugs. PMID- 8345005 TI - Knowledge and compliance with medications in South East Asian refugees. AB - We evaluated knowledge about prescribed medications and compliance with taking those medications in 96 South East Asian refugees of different ethnic backgrounds seen in a primary care clinic. Two hundred and thirty (88%) of 262 prescribed medications were currently being taken by the patients. Although 97% of the medications were either named or described correctly, the correct rationale for taking the medication was known for only 79% and the correct dosage regimen for only 63%. Thirty-two (33%) of the 96 patients were not taking one or more of their prescribed medications, 17 (18%) were taking one or more medications not prescribed, 5 (5%) were taking duplicate forms of the same medication, and 4 (4%) were taking a medication that had been discontinued by the clinic provider. Seventy-two (75%) patients were taking one or more medications at an incorrect dose. Only 12 (12%) patients were fully compliant with all prescribed medications. We conclude that knowledge about and compliance with medications is a major problem among South East Asian patients attending a primary care refugee clinic. PMID- 8345006 TI - High-performance liquid chromatographic determination of perphenazine in plasma. AB - A reversed-phase high-performance liquid chromatographic (HPLC) method for the analysis of perphenazine in rabbit plasma was developed. Amitriptyline HCl was used as the internal standard. The chromatography was performed using a Microsorb CN column; the mobile phase consisted of 85:15 methanol/0.005 M ammonium acetate buffer; flow rate of 1.6 ml/min; and ultraviolet detection at 254 nm. Retention times were 10.8 and 18.1 min for perphenazine and amitriptyline HCl, respectively. The recovery of perphenazine added to plasma in the concentration range of 0.05-5 micrograms/ml was found to be greater than 80%. This procedure was used for the analysis of plasma samples collected over time following the oral administration of perphenazine tablets in rabbits. PMID- 8345007 TI - Comparison of the effectiveness of two oral phenytoin products and chronopharmacokinetics of phenytoin. AB - A cross-over study was carried out in 14 epileptic patients to compare the steady state serum phenytoin concentrations produced by two phenytoin formulations (Phenytoin Sodium and Epanutin). Differences in steady-state phenytoin concentrations following a change from one product to the other were not significant, indicating that the two brands manifest equivalent therapeutic efficacy. The results suggest that no overall dosage adjustments are required when switching from one brand to the other. Chronopharmacokinetic parameters of a single 300-mg dose of phenytoin, given at 08.00 and 20.00 hours, were studied in 10 healthy, male volunteers under controlled conditions. No evidence was found that circadian rhythms influenced absorption and disposition. PMID- 8345008 TI - [Wounding of an iliac artery during celioscopy]. AB - Vascular accidents during celioscopy are rare but potentially serious. Arterial injuries usually involve the aortic bifurcation and are generally recognized and treated as emergencies. In the present case, a transfixing wound of the right common iliac artery provoked by a trocar during gynecological celioscopy in a 36 year old woman was diagnosed secondarily, the posterior orifice being unrecognized during laparotomy to control hemorrhage. A false iliac artery aneurysm was detected 2 months later when she presented signs of a compressive retroperitoneal hematoma confirmed by arteriography and scan images. The common iliac artery was ligatured through a right retroperitoneal approach with extra anatomical revascularization by a crossed iliofemoral venous shunt. The postoperative course was uncomplicated apart from a right cruralgia sequela. Immediate circumferential dissection for treatment of aortic bifurcation injuries is recommended, to avoid missing a transfixing wound, and to allow direct restoration usually by simple suture. In contrast, secondary treatment is complex, raises problems of arterial reconstruction, and cannot always prevent functional sequelae. PMID- 8345009 TI - [Place of pelvic exenteration in the treatment of recurrence of cancer of the uterine cervix]. PMID- 8345010 TI - [A rare form of internal hernia: hernia of the sigmoid mesocolon]. AB - An internal hernia of sigmoid mesocolon provoking an occlusive syndrome is described, and the different types of hernia of sigmoid mesocolon analyzed and discussed. The diagnosis of these rare (5% of cases) internal hernias is established frequently at operation only, their treatment, always surgical, being simple when instituted in their early stages. PMID- 8345011 TI - [Place of super-selective vagotomy in the treatment of perforated duodenal ulcer]. AB - Thirty-two duodenal ulcer perforations were treated by suture and supraselective vagotomy. Perioperative mortality was nil. The recurrence rate was 6.2% against 17% after elective supraselective vagotomy performed by the same surgeons during the same period. Results of this technique for treatment of perforated duodenal ulcer are compared with those of 28 simple sutures and 32 truncal vagotomies. PMID- 8345012 TI - [A method of intraoperative colonic irrigation during appendectomy]. PMID- 8345013 TI - [Internal hernia of the abdomen. Apropos of 14 cases]. AB - Internal abdominal hernias develop when one or more viscera extrude through an intraperitoneal orifice but remain within the peritoneal cavity. The orific may be normal (Winslow's foramen) or paranormal (peritoneal fossae: paraduodenal, ileocecal, inter- and mesosigmoidal, paracolic, supravesical, of the large ligament of uterus). All these hernias possess a sac and are true hernias. The orifice may also be abnormal: pathologic origin if formed in a mesentery or an omentum (trans-mesenteric, trans-mesocoloic, trans-omental, by colo-omental disinsertion) or in the form of an anomalous orific if it occurs in a congenital anomaly of a ligament (falciform ligament of liver) or a mesentery (mesentery of Meckel's diverticulum): all these hernias lack a sac and are "internal prolapses or procidentia". Of the 14 cases presently reported, 6 were hernias through a paranormal orifice: 2 left and 2 right paraduodenal, 1 intra-mesosigmoidal and 1 retrocecal; 6 were hernias through a pathologic orifice: 2 trans-mesenteric, 1 in the posterior cavity through a colo-omental dissinsertion hole and 3 trans omental, and 2 were hernias through an anomalous orifice from absence of the falciform ligament of liver. Incidence of these hernias reported in the literature is between 0.2 and 0.9% of autopsies and 0.2 and 2% of parietal hernias, findings in our series being 0.098% (14 of 14,199 cases) of laparotomies and 0.32% (14 of 4,374 cases) of parietal hernias. Of 1,871 cases described in the occidental or near occidental literature (in French, English, Italian or German), 160 (8.55%) were hernias through Winslow's foramen, 1035 (55.31%) through a para-normal orifice and 676 (36.1) through an abnormal orifice (pathologic and anomalous). The sex ratio showed a male prevalence (3:2), age distribution demonstrating the onset of internal hernias at all ages with a preference for the 5th decade and a mean age of 46 years. Symptomatology was totally non specific, subacute to acute occlusive symptoms or even signs of already installed necrotizing-peritonitis being detected in 80 to 90% of cases. In 10 to 15% of patients the hernia was an unexpected finding during laparotomy for another affection, an almost typical feature of the largest para-normal hernias, the paraduodenal hernias. Preoperative diagnosis is practically impossible, and in many cases cannot be made because of time restriction, but it is sometimes possible with the largest hernias after a longer sub-occlusive period by radiologic, arteriographic and scan imaging. However, the primary task of the surgeon is not so much to establish the diagnosis as to assess the need for urgent operation. Hernias provoking large displacements of viscera can even make intraoperative diagnosis difficult with subsequent errors, and surgeons must recognize all possible types of these hernias, especially those passing through a para-normal orifice, and must be able to pinpoint the fixed guiding points. They must also work in as large an operative field as possible and should therefore always start by a median infra-supra-umbilical laparotomy to allow its maximum extension. Reduction of herniated viscera can be simple, by gentle traction, or difficult requiring dilatation of the hernial orifice and/or opening of the sac.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345014 TI - [Contribution of imipenem/cilastatin in the treatment of peritonitis: a comparative economic analysis in the case of France]. AB - Imipeneme, a molecule chemically related to the carbapenems (beta-lactam), is a potent wide spectrum antibiotic reserved for hospital use. Effective as therapy for major infections, and for use in severely debilitated patients (immunodepressed, etc ...) its efficacy in the treatment of peritonitis has been demonstrated in numerous studies abroad, confirmed by results of a French multicenter trial in 1989. Its cost-effectiveness ratio was assessed as excellent in a comparative case-controlled study of totally matched patients treated with other antibiotics. As expected, the cost of the treatment itself (imipeneme/cilastatine plus associated products and costs of their administration) was higher by about 1000 F per patient when compared with other antibiotic regimens, but its markedly superior efficacy allowed overall economies of about four and a half times this sum (4300 F). This cost reduction was related to different factors, some of which could not be individualized because of missing data (personnel) or protocol bias (laboratory examinations). Nevertheless, the global result was a shortening of hospital stay by more than two days due to a very pronounced decrease in failure rate of the first treatment. This result is even more remarkable in that the peritonitis treated by Tienam was significantly more severe than that treated by the other antibiotics. PMID- 8345015 TI - [Escherichia coli septicemia revealing acute appendicitis. Apropos of a case]. PMID- 8345016 TI - [Echinococcosis of the iliac bone. Apropos of a case]. PMID- 8345017 TI - [Severe complications after cholecystectomy by celioscopy: lessons from yesterday and today]. AB - The case of a series of grave complications after a laparoscopic cholecystectomy is reported: a common bile duct section diagnosed rather late, hemoperitoneum, inappropriate common bile duct reconstruction and late anastomic leakage, stenosis of an hepatico-jejunal anastomosis, haemorrhage through the external biliary drainage and iterating sepsis. The final outcome was good. The stenotic hepatico-jejunal anastomosis was dilated by a Gianturco self-expanding prosthesis percutaneously placed. As an evidence, this alternative treatment is only exceptional, the treatment of choice for postsurgical benign strictures being surgical repair. PMID- 8345018 TI - [Radiotherapy in cancer of the rectum]. AB - The response of adenocarcinoma of rectum to radiotherapy is dependent on the use of irradiation techniques that ensure a sufficient dose be applied to the tumor without exceeding tolerance limits of pelvic tissues. This has been clearly demonstrated by results of contact radiotherapy over the last 30 years or so. Doses of about 100 Gy provide local control in 90% of cases and a 5 year survival rate of 80% in patients with highly selected tumors. For several years now, contact radiotherapy has been associated with external irradiation and iridium therapy with resulting sterilization of T2 and even T3 or N1 tumors in inoperable cases. Endorectal ultrasound imaging is essential for selecting those patients requiring radiotherapy alone and for evaluating the results, but in more than 90% of patients, surgery remains basic treatment for cancer of rectum. The incidence of local recurrence, very difficult to treat, is non negligible, however, but combining radiotherapy with surgery has been shown to reduce the rate of by 50%. Opinions differ on the relative efficacy of pre- or post-operative radiotherapy, but tolerance to this treatment is good in both cases if the technique used limits radiation to the posterior pelvis. Results of a Swedish randomized trial demonstrated greater efficacy for pre-operative radiotherapy for controlling local spread. Meta analysis showed that irradiation produces a definite gain in local control with a resulting gain in survival of about 5 to 10%. In the USA, chemotherapy based on 5 FU combined with post-operative radiotherapy was equally favorable in terms of survival. Pre-operative radiotherapy may also increase the chance of conservation of the sphincter. Although numerous points concerning chronology and mode of treatment remain open to discussion, a combination of radiotherapy and surgery now appears as standard treatment for rectal cancer. PMID- 8345019 TI - [Choledochoduodenal anastomosis by laparoscopy]. AB - Eleven patients underwent choledochoduodenostomy under laparoscopic control: 5 for adenocarcinoma of head of pancreas, including 2 with extension into duodenum, 3 for chronic pancreatitis. 1 for gastric carcinoma with pancreatic infiltration 1 for carcinoma of ampulla and 1 for stenosing papillitis. Mean duration of operation was 97.9 minutes and mean hospital stay 7.8 days. No immediate or delayed postoperative complications were reported. The advantages of this method are the marked reduction in recovery time, especially in severely debilitated elderly patients, and the absence of postoperative pain. PMID- 8345020 TI - [Boerhaave syndrome or spontaneous rupture of the esophagus]. AB - Spontaneous rupture of esophagus is a rare affection resulting from barotrauma to lower esophagus during the effort of vomiting. The diagnosis is suggested by the presence of violent retrosternal pain after a bout of vomiting following the partaking of a copious meal by an alcoholic patient. Prognosis is dependent on the rapidity of treatment, always surgical and completed by long-term antibiotic therapy. Complementary examinations should be limited to a standard chest x ray and esophageal imaging with water-soluble contrast. Recovery is now the rule for patients treated within 24 hours. Mortality is high in patients diagnosed at a late stage, but this could be reduced by improved recognition of the syndrome. PMID- 8345021 TI - [An unusual complication of perforated sigmoid diverticulitis: gas in the portal vein with miliary liver abscesses]. AB - A patient presented with gas in the portal vein and miliary liver abscesses due to perforation of a sigmoid diverticulitis abscess. The outcome was favorable after surgical treatment. Gas in the portal vein, a sign of extreme seriousness, is generally the result of intestinal necrosis from ileo-mesenteric artery infarction, responsible for more than 75% of deaths. Diagnosis of this exceptional complication, suggested from a straight abdominal film, was confirmed by hepatic ultrasound and scan imaging. Urgent surgical intervention can hopefully, as in the present case, result in the patient's survival. PMID- 8345022 TI - [Peritonitis caused by rupture of a retroperitoneal abscess]. AB - A 30 year old man presented with an initial clinical picture limited to low back pain. Increasing severity of the pain after one month led to his admission to a surgical department and the diagnosis of a large right retroperitoneal abscess. Several hours before the proposed operation for extraperitoneal surgical drainage of the abscess through a lumbar approach, his condition was complicated by the intraperitoneal rupture of the abscess. The resulting peritonitis and the retroperitoneal abscess were treated through a laparotomy and the postoperative course was uncomplicated. A literature review showed this to be only the second case of this rare generalized peritonitis complication to be reported, for which a parallel can be drawn with the intraperitoneal rupture of a pyonephrosis. A general overview of retroperitoneal abscesses is presented. PMID- 8345023 TI - [Therapeutic problems of cancers of the gallbladder]. AB - Data of 32 patients who were operated for gallbladder carcinoma were evaluated in a retrospective meta-analysis. Results were compared with endoscopic retrograde cholangio-drainage (ERCP) using large size 12/14-French gauge endo-prostheses with side flaps to prevent migration. According to the TNM classification 84% of patients were classified as stage IV, 12.5% were in a stage III and 3% were in a stage II. Only 22% of cases were operated for cure (cholecystectomies, lymphadenectomy, wedge resection of the liver). All patients died in between one year on cancer, average survival was 158 days in TNM stage II, 183 days in stage III and 75 days in stage IV. Early complication rate was in stage III and 75 days in stage IV. Early complication rate was at 28% due to cardiac and pulmonary complications. No one died as a result of the operation. Endoscopic bile duct drainage (ERCP) for gallbladder carcinoma (n = 21) was shown to be superior to surgical results with an average survival of 160 days. Early complication rate (30 day interval) was at 5.6% (n = 1014), mostly due to tube occlusion with cholangitis; clinical mortality was 2.6% only (n = 393). Occlusion of the endoscopic 12/14-French gauge tube was seen after 213 days in average. Endoscopic therapy was shown to represent an independent way in gallbladder cancer treatment not only for patients defined as not suitable for operation. All own results were compared to the literature, therapeutic regimen in gallbladder carcinoma is summarized as an organigramm. PMID- 8345024 TI - [Internal hernias of the abdomen. Apropos of 14 cases]. PMID- 8345025 TI - [Agenesis of the gallbladder diagnosed by celioscopy]. PMID- 8345026 TI - Analysis of multiple sugar probes in urine and plasma by high-performance anion exchange chromatography with pulsed electrochemical detection. Application in the assessment of intestinal permeability in human immunodeficiency virus infection. AB - Mannitol, 3-O-methylglucose and lactulose administered orally are used to investigate small intestinal absorption pathways and mucosal integrity. Current methods of analysis include thin-layer chromatography, gas chromatography (GC) and enzymatic analysis, which require separate estimation of mono- and disaccharides and for GC, prior derivatization. We describe a high-pressure anion exchange chromatographic method coupled with pulsed electrochemical detection allowing simultaneous measurement of all three sugars and its clinical application in monitoring intestinal damage in human immunodeficiency virus (HIV) infection. Sample preparation is simple and fast. All sugars are resolved within 10 min. Mean recovery is 93.3% for all sugars and the overall relative standard deviation is 4.2%. Intestinal permeability (lactulose/mannitol ratio) rises with disease progression to AIDS, indicating mucosal damage. The greatest increase in permeability is associated with chronic diarrhoea. The method is an ideal non invasive test to assess gut mucosal damage in HIV infection. PMID- 8345027 TI - Analysis of cationic nutrients from foods by ion chromatography. AB - This paper describes the feasibility of combining two relatively new technologies to generate data on the cationic nutrient content of foods. Single-column ion chromatography was used to monitor several analytes following the use of a microwave digestion scheme aimed at rapid, multiple sample digestion. The result is a more streamline and productive approach to multi-sample preparation and multi-analyte determination when investigating the cation content of foods. Linearity and limits of detection for the chromatographic procedure were established. Sample size as well as digestion acid type and amount were investigated during the microwave process. The method was applied to a variety of food matrices to evaluate its scope. Results generated with this method compare favorably to those from atomic absorption. Finally, capillary ion electrophoresis (Waters' trade name: Capillary Ion Analysis), a subset of capillary electrophoresis which has been optimized for ion analysis, was applied to the sample digests to investigate the usefulness of this technology to the analysis of mono-/divalent cations from foods. PMID- 8345028 TI - Effect of temperature on the salt balance of milk studied by capillary ion electrophoresis. AB - Many inorganic species, such as calcium, phosphate and magnesium, are in equilibrium between the liquid and colloidal phases of milk and hence are of importance with respect to the coagulation properties of milk. Capillary ion electrophoresis makes possible the determination of anions and cations in less than 6 min. The soluble phase of milk was obtained by ultrafiltration and samples had to be diluted 250-fold before analysis. Cold storage increased soluble calcium and phosphate concentrations, and warm-up of the milk restored the initial ionic equilibria. More drastic heat treatments (80-90 degrees C) caused precipitation of tricalcium phosphate and calcium citrate. PMID- 8345029 TI - Clinical review 48: The current status of diagnosis and therapeutic intervention in Turner's syndrome. PMID- 8345030 TI - Of scid mice and men. PMID- 8345031 TI - Preservation of functioning human thyroid organoids in the scid mouse: 1. System characterization. AB - We have characterized a system for preserving reconstituted human thyroid follicles in vivo by transplanting human thyrocytes into mice with severe combined immunodeficiency (scid mice). Human thyroid organoids were constructed from thyroid monolayer cells derived from both normal and abnormal thyroid tissue, and embedded within a basement membrane preparation which was then transferred sc to scid mice. As early as 4 weeks, and as late as 3 months post transplantation, histological examination of human thyroid organoids demonstrated widespread neofollicle formation and colloid accumulation which stained positive for human thyroglobulin (hTg). Although there were no changes in murine serum T4 levels; the transplanted thyroid epithelial cells secreted hTg into the scid mouse circulation (with an average level of 29 micrograms/L). In addition, hTg release was stimulated in vivo by ip administration of recombinant human TSH (0.1 1.0 IU/mouse) achieving greater than 20-fold increases in scid mouse serum hTg levels. In situ immunohistochemistry showed that thyroid organoids derived from patients with Graves' disease retained scattered lymphocytes in peripolesis with the thyroid epithelial cells; those lymphocytes were identified as human T cells of the memory (CD45RO +), rather than naive, type. These data demonstrate that functioning human thyroid organoids establish in scid mice and remain responsive to TSH stimulation. The system offers a unique opportunity to examine human thyroid-lymphocyte interaction within the confines of a predictable animal model. PMID- 8345032 TI - Preservation of functioning human thyroid organoids in the scid mouse: II. Biased use of intrathyroidal T cell receptor V genes. AB - The severe combined immunodeficiency (scid) mouse, which lacks functional B cells and T cells, has proven a useful model for exploring the survival of transplanted human lymphocytes and thyrocytes. In order to further characterize T cell infiltrates in reconstituted sc human thyroid organoids, we examined for the presence of 18 human T cell receptor (hTcR) V alpha and 21 hTcR V beta gene families using polymerase chain reaction (PCR) analysis. Human TcR V gene activity was confirmed by Southern blot analysis of the PCR fragments from all but one of the thyroid organoids, confirming the continued survival of human T cells within the thyroid organoids. However, only 3.5 out of 18 V alpha and 5.9 out of 21 V beta gene families were detected in these human thyroid organoids indicating a marked bias in T cell survival. Sequencing of the V-D-J regions of the amplified TcR fragments showed that approximately 60% of the sequences were representative of clonally expanded T cells. Hence, these passenger T cells exhibited highly biased use of particular TcR V gene families similar to that observed previously in thyroid tissue and intrathyroidal T cell cultures. Furthermore, variations in the V-D-J regions of sequences from similar V gene families indicated that the V gene region was important in T cell selection rather than the CD3 region. PMID- 8345033 TI - Estrogen synthesis inhibitors: from "off the rack" to haute couture. PMID- 8345034 TI - Open dose-finding study of a new potent and selective nonsteroidal aromatase inhibitor, CGS 20 267, in healthy male subjects. AB - The aim of this open, dose-finding study was to evaluate the effects of single dose CGS 20 267, a new oral nonsteroidal aromatase inhibitor, on the inhibition of estrogen production and also on the production of adrenal and testicular steroids in healthy male subjects. Nine dose levels ranging from 0.02-30 mg and placebo were tested, each dose being given to 3 subjects only. A total of 18 subjects were included; 12 of them received 2 single administration, the remaining 6 were exposed only once to one of the 2 highest dose levels. A reduction in serum estrogen levels when compared to baseline was already observed after 2 h, reaching maximum suppression between 10 and 48 h after administration. After 24 h, a suppression of estrone levels by 60-85% from baseline was achieved with all tested doses. A reduction in estradiol levels by about 30% from baseline was observed at the lowest dose (0.02 mg). This reduction was further enhanced dose dependently to a maximum of about 90% from baseline at 24 h after administration of the highest dose (30 mg). With the higher doses (10 and 30 mg), estrogen suppression was maintained up to 3 days. A dose-dependent increase of testosterone, LH, and FSH was observed and was most pronounced in the 10- and 30 mg dose groups, which can be considered as a consequence of the long-lasting aromatase inhibition achieved with these high doses. No effect on serum cortisol and aldosterone levels was observed up to the highest dose. No clinically relevant changes were observed in blood chemistry and hematology tests. The systemic and subjective tolerability of CGS 20 267 was good at all doses. This study has shown that CGS 20 267 is a well tolerated, potent, selective, and long acting inhibitor of the aromatase enzyme after single administration. PMID- 8345035 TI - Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in healthy postmenopausal women. AB - We have performed a phase I study of the effect of a single dose of CGS 20267, an oral nonsteroidal aromatase inhibitor, in 12 healthy volunteer postmenopausal women. Each subject received 2 single doses of CGS 20267 (0.1, 0.5, or 2.5 mg) or placebo separated by a washout period of at least 6 weeks. There was statistically significant suppression of serum estrone and estradiol at all three doses of CGS 20267 tested. Serum estrone and estradiol concentrations were maximally suppressed by 76% and 79% from baseline levels, respectively. Urinary excretion of estrone and estradiol was also suppressed, although this did not reach statistical significance. Serum concentrations of aldosterone, cortisol, 17 alpha-hydroxyprogesterone, androstenedione, testosterone, FSH, LH, and TSH were unaffected by CGS 20267. The drug was well tolerated, with no significant side effects. This study has shown CGS 20267 to be a potent and specific aromatase inhibitor, and further studies are now needed to assess its clinical efficacy. PMID- 8345036 TI - Thyrotoxicosis and the heart: something old and something new. PMID- 8345038 TI - Is hypothalamic-pituitary-adrenal hyperactivity important in the pathogenesis of excessive abdominal fat distribution? PMID- 8345037 TI - Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine. AB - To investigate the effects of long term thyroid hormone suppressive therapy on the heart, 20 patients were evaluated by noninvasive techniques. Of them, 10 were athyreotic after surgery for differentiated thyroid cancer, and 10 had diffuse or nodular goiter. The mean age of the group was 39 +/- 11 yr. Twenty age- and sex matched subjects served as controls. The mean dose of levothyroxine was 163 +/- 34 micrograms daily. Plasma TSH was undetectable in all patients. Mean serum T4, free T4, and sex hormone-binding globulin were significantly higher (P < 0.001), whereas mean serum T3, free T3, and osteocalcin did not differ from control levels. Cardiac evaluation consisted of a standard 12-lead electrocardiogram, an ambulatory electrocardiographic monitoring (Holter), and an echocardiographic study. Two patients showed abnormal electrocardiograms for left ventricular hypertrophy. Holter demonstrated an increase in average heart rate (84 +/- 7 vs. 70 +/- 6 beats/min; P < 0.01). Prevalence of atrial premature beats was higher in the patient group than in the control group (100% vs. 60%; P < 0.006). The echocardiogram showed an increased left ventricular mass index in the patient group (97 +/- 24 vs. 80 +/- 18 g/m2; P < 0.02). Furthermore, left ventricular systolic function was enhanced, with higher values of fractional shortening (38 +/- 7% vs. 34 +/- 4%; P < 0.05) and rate-adjusted velocity of shortening (1.2 +/- 0.13 vs. 1.05 +/- 0.14 circumferences/sec; P < 0.01). These findings indicate that long term levothyroxine therapy at suppressive doses markedly affects cardiac function. PMID- 8345039 TI - Analysis of 24-hour plasma profiles of growth hormone (GH)-binding protein, GH/GH binding protein-complex, and GH in healthy children. AB - Human blood contains a high affinity GH binding protein (GHBP) which corresponds to the extracellular domain of he GH-receptor. It has been suggested that GHBP can modify the biological actions of GH, and alter the distribution of GH in the body. To study the hormonal regulation of growth, it is therefore necessary to measure GHBP as well as GH. We recently developed a ligand-mediated immunofunctional assay (LIFA) which allows separate quantitation of total GHBP (free and GH-bound) and the complex formed by GH and GHBP (GH/GHBP-complex) in human blood. We have now used the ligand-mediated immunofunctional assay to measure GHBP levels in plasma profiles from healthy children. GH was measured by immunoradiometric assay. Fifteen 24-h plasma profiles from 12 healthy children (3 girls and 9 boys) of different ages (6-15 yr), heights (-2.5 to +3.0 SD scores) and pubertal stages (1-4) were examined. Blood was withdrawn continuously for 24 h and collected in 20-min fractions. Time series for GH, GHBP, and GH/GHBP complex were analyzed by cross-correlation and Fourier analysis. GH was secreted in a pulsatile fashion in all subjects. The concentration of the GH/GHBP-complex varied during the sampling period, and the changes correlated significantly with the GH pulses with correlation coefficients reaching maximum at zero time lag. In contrast, the changes in the total GHBP concentration were minor (coefficients of variation approximately 10%), and not correlated to GH pulses. Fourier analysis showed similar spectral power patterns for GH and GH/GHBP-complex, suggesting a diurnal rhythm (12- to 24-h periods) as well as components of higher frequencies (around 4-h periods). Although there were only subtle fluctuations in the total GHBP concentration, Fourier transformation revealed a diurnal rhythm with nadir during the night, while components of higher frequencies were much less abundant. We conclude that variations in total GHBP as measured by LIFA during a 24-h sampling period are small and that the concentration can be estimated from a single random blood sample. PMID- 8345040 TI - Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the prolonged effects of radiation on the thyroid. AB - The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. We have identified 4296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3843 subjects. Of the 2634 subjects who have been found, 1043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodules within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and our screening program, which began in 1974, we compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr. PMID- 8345041 TI - Thyroxine interactions with transthyretin: a comparison of 10 different naturally occurring human transthyretin variants. AB - Transthyretin (TTR) is a tetrameric protein that transports 15-20% of circulating T4. Alterations in TTR structure can manifest clinically as familial amyloidotic polyneuropathy or euthyroid hyperthyroxinemia. We have measured the relative affinity for T4 of several variant TTR molecules in human plasma. We have compared control plasma to plasma from a patient heterozygous for a [Thr109]TTR mutation associated with a 3-fold increased affinity for T4 and to plasma from patients with familial amyloidotic polyneuropathy with different point mutations in TTR. Relative affinity was measured in an assay in which [125I]T4 bound by TTR was isolated by immunoprecipitation with an antibody specific for TTR. [Thr109]TTR displayed the highest affinity for T4, whereas homozygous [Met30]TTR did not bind appreciable amounts of [125I]T4. The rank order of affinity of the various TTR mutations for T4 was: Thr109 heterozygous > wild type = Ala60 heterozygous = Ile122 heterozygous > His58 heterozygous approximately Tyr77 heterozygous approximately Ser84 heterozygous approximately Ile122 homozygous approximately Met30 heterozygous >> Met30 homozygous TTR. Thus, different point mutations in TTR increase, decrease, or do not affect TTR's affinity for T4. The ability of TTR to form amyloid fibrils does not appear to be related to its affinity for T4. Further study is required to define the molecular basis of alterations in T4 binding induced by point mutations located along the TTR tetramer. PMID- 8345042 TI - Carbohydrate metabolism and urinary excretion of calcium and oxalate after ingestion of polyol sweeteners. AB - Polyols are widely used instead of glucose and sucrose in sweets and dietary products because they are barely cariogenic, and their energy value is lower. In addition, it has been shown that calciuria and oxaluria increase after an oral glucose (Glu) load. We, therefore, investigated the effects of a single polyol ingestion on carbohydrate, calcium, phosphate, and oxalate metabolism in 10 healthy subjects. On 5 experimental days, subjects ingested 20 g Glu, Lycasin (Lyc), Maltisorb (Mal), sorbitol (Sor), or xylitol (Xyl). Glu, Lyc, and Mal intake caused an increase in glycemia [respectively, +34% (P < 0.001), +15% (P < 0.001), and +15% (P < 0.001)], insulinemia [respectively, +358% (P < 0.001), +88% (P < 0.05), and +94% (P < 0.01)], and C-peptide level [respectively, +170% (P < 0.001), +15% (P < 0.01), and +15% (P < 0.001)]. Conversely, no change occurred in glycemia, insulinemia, or C-peptide levels after ingestion of Sor or Xyl. Urinary calcium increased after Glu (+64%; P < 0.01) and Xyl (+74%; P < 0.01) intake, and urinary phosphate increased after Xyl (+27%; P < 0.05), but decreased after a Glu load (-68%; P < 0.01). Only Xyl increased urinary excretion of oxalate (+53%; P < 0.05). Our results suggest that ingestion of polyols causes a much lesser pancreatic stimulation than Glu intake. Also, Lyc, Mal, and Sor sweeteners have no effect on urinary excretion of calcium and oxalate, whereas calciuria and oxaluria increase after Xyl ingestion. PMID- 8345043 TI - Variable carbohydrate structures of circulating thyrotropin as studied by lectin affinity chromatography in different clinical conditions. AB - Carbohydrate structures of intrapituitary and circulating TSH were studied by Concanavalin-A (Con A) and ricin lectin chromatography under different clinical conditions. Con A permits the separation of molecules differing in the extent of their carbohydrate branching, whereas ricin gives an estimation of the degree of their sialylation. Intrapituitary TSH was more retained on Con A and less sialylated than circulating hormone, suggesting that carbohydrate chains of intrapituitary molecules are less mature than those present in the circulation. A greater proportion of TSH firmly bound to Con A, compared to control values, was found in sera from fetuses and patients with uremia, TSH-secreting adenomas, and central hypothyroidism. In primary hypothyroid patients, TSH binding to Con A was similar to that found in controls, but a greater percentage of sialylated forms was seen. In central hypothyroidism patients, TSH released in response to TRH was less sialylated. Interestingly, no sialylated TSH was found in normal fetuses. In conclusion, the present data show that both TSH carbohydrate branching and sialylation may vary in different clinical conditions. As some of the above clinical conditions are known to be accompanied by variations in the bioactivity of circulating TSH, the finding of changes in TSH carbohydrate structures further supports the view that glycosylation modulates the expression of TSH biological activity. PMID- 8345044 TI - Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis. AB - Preliminary reports suggest that PTH is secreted in a pulsatile fashion. However, available studies have not attempted to calculate actual PTH secretion rates in healthy individuals. To accurately characterize PTH secretory dynamics in healthy subjects, we studied seven young women and six young men, all of whom had hip and spine bone densities by dual photon densitometry in the upper tertile for age matched control subjects. PTH concentrations were measured by immunoradiometric assay in blood sampled every 2 min over 6 h. Ionized calcium levels were obtained during the second and third hours of the study. Plasma PTH profiles were subjected to deconvolution analysis, which resolves measured hormone levels into secretion and clearance components. Cross-correlation analysis was performed to assess direct or inverse correlations between serum PTH and ionized calcium concentrations at various time lags. In these subjects, PTH was secreted in a dual fashion, with significant basal (tonic) secretion and PTH pulses approximately every 20 min. Pulsatile PTH secretion accounted for approximately 25% of the total secreted PTH. There were no differences in PTH secretory parameters between men and women, nor were there any significant correlations between PTH and ionized calcium concentrations. We conclude that in normal subjects, the predominant mode of PTH secretion is tonic, with superimposed PTH pulses of small amplitude but high frequency. The clinical significance of this complex physiological pattern of secretion awaits further study. PMID- 8345045 TI - Carboxyl-terminal fragments of parathyroid hormone are not secreted preferentially in primary hyperparathyroidism as they are in other hypercalcemic conditions. AB - Calcium infusion in normal men decreases immunoreactive PTH (iPTH). Intact iPTH (I) shows the greatest decline, and there is a greater decrease in carboxyl terminal iPTH (C) than in midcarboxyl-terminal iPTH (M); thus, C/I, M/I, and M/C ratios are increased. To verify whether this adaptive mechanism to hypercalcemia was present in patients with primary hyperparathyroidism (PHP), we measured total serum calcium (Ca), I, C, and M as well as C/I, M/I, and M/C ratios in 32 normocalcemic normal subjects (NN), in the same normal subjects made hypercalcemic (HN), in 31 patients with PHP, and in 12 patients with nonparathyroid hypercalcemia (NPHN). Eight patients with PHP and the 32 NN were submitted to CaCl2 and Na2 EDTA infusions to evaluate their parathyroid function. Ca was lower (P < 0.005) in NN (2.21 +/- 0.06 mmol/L) than in PHP (2.80 +/- 0.25 mmol/L) or NPHN (2.83 +/- 0.20 mmol/L). The HN Ca value (2.80 +/- 0.18 mmol/L) was similar to those in PHP and NPHN subjects. C, M, and I were increased in PHP compared to the other groups (P < 0.005). PHP had C/I and M/I ratios of 2.03 +/- 0.72 and 9.04 +/- 7.69, values similar to NN (2.29 +/- 0.55 and 8.70 +/- 3.0), but lower than HN (5.36 +/- 2.48 and 25.93 +/- 13.86; P < 0.005) and NPHN (11.91 +/- 13.06 and 18.69 +/- 10.81; P < 0.005). NPHN also had a lower M/C ratio than HN (2.76 +/- 2.02 vs. 4.99 +/- 1.81; P < 0.05). PHP and NN could increase their C/I ratio to the same maximum (4.71 +/- 1.26 vs. 5.70 +/- 2.94), but PHP did so at a much higher set-point (2.67 +/- 0.19 vs. 2.24 +/- 0.10 mmol/L; P < 0.005). PHP also had higher set-points for M/I, and M/C ratios even if they failed to increase the ratios to the high values in NN [M/I 11.6 +/- 6.4 vs. 29.3 +/- 18.3 (P < 0.005); M/C, 2.16 +/- 1.20 vs. 5.0 +/- 1.93 (P < 0.005)]. Thus, carboxyl terminal fragments are not secreted preferentially in PHP as they are in other hypercalcemic conditions. This relates to a higher set-point for the regulation of C/I and M/I ratios, permitting the secretion of more intact hormone relative to C or M fragments. The lower M/C ratio in NPHN and in PHP made more hypercalcemic compared to HN suggests a lower production or a higher clearance of midcarboxyl-terminal fragments in chronic hypercalcemia. PMID- 8345046 TI - Pulsatile luteinizing hormone patterns in long term oral contraceptive users. AB - Oral contraceptives (OC) inhibit folliculogenesis by a central suppressive action on the release of gonadotropins. To characterize the nature of these central effects, we studied 40 long term OC users on 3 different OCs: two monophasic preparations with 30 micrograms ethinyl estradiol and 150 micrograms l-norgestrel (group 1; n = 15), 150 micrograms desogestrel (group 2; n = 10), and a triphasic formulation containing 30-40 micrograms ethinyl estradiol and 50, 75, and 125 micrograms l-norgestrel (group 3; n = 15). Blood sampling at 10-min intervals during 6-h periods was performed at different moments in the pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. FSH and LH were measured by a sensitive immunoradiometric assay. Pulsatile LH release was observed in all OC users. Mean serum LH and FSH levels, number of LH pulses per 6 h, and the amplitude of LH pulses on day 1 of the pill cycle did not differ from early follicular phase control values. FSH levels were rapidly suppressed from day 2 onward in all three groups, whereas LH levels progressively declined in groups 1 and 2 from day 8 onward. In group 3, however, LH levels were only significantly suppressed after day 13. The number of LH pulses per 6 h decreased in all groups starting on day 2, whereas the amplitude of LH pulses increased. A substantial percentage of LH pulses observed in OC users after day 1 were of low amplitude (< 0.75 IU/L). From these results, we conclude that 1) pulsatile release of LH is maintained during OC use; 2) FSH levels are suppressed equally early and equally effective by all OCs studied; 3) during OC use, the number of LH pulses per 6 h is reduced; 4) modulation of LH pulse amplitudes, and subsequently of serum LH levels, is mainly mediated by a dose- and time-dependent effect of the gestagenic component of the OC; and 5) after the 7-day pill-free interval, a normal early follicular phase pulse pattern is found, even in long term OC users, suggesting that in this period, most of the steroidogenic feedback effects wear off. PMID- 8345049 TI - Role of estradiol in the rise in follicle-stimulating hormone levels during the luteal-follicular transition. AB - Follicular recruitment takes place under FSH stimulation at the end of the luteal phase and the beginning of the subsequent follicular phase, the so-called luteal follicular transition (LFT). Inhibin, a known suppressor of FSH, has been implicated in the onset of the rise in FSH levels, as the fall in its immunoreactive plasma levels after the demise of the corpus luteum has been shown to correlate negatively with the increase in FSH. To analyze the role of estradiol (E2), another inhibitor of FSH secretion in the LFT, we designed an experimental paradigm to dissociate the physiological falls in inhibin and E2. This was achieved by extending the duration of luteal plasma E2 levels with transdermal E2 treatment. Untreated ovulatory cycles in seven healthy female volunteers, aged 28-38 yr, were compared with E2-treated cycles in the same subjects, with treatment starting on the 10th day after the LH surge and continuing through the 4th day of the following menses [either 0.2 mg (n = 6; G1) or 0.1 mg (n = 6; G2) E2 daily]. Blood samples were obtained daily from the LH surge until the 11th day of the next cycle. Immunoreactive plasma inhibin levels reached a nadir on day 2 of menses regardless of whether women received E2. Plasma E2 (mean +/- SEM) levels remained within the normal luteal range (220 +/- 51 to 635 +/- 279 pmol/L) until the end of the treatment period in G2 (range, 253 +/- 40 to 382 +/- 62 pmol/L), but not in G1 (range, 598 +/- 195 to 1835 +/- 1259 pmol/L). However, the onset of the FSH rise was clearly delayed, from a mean of 2 days before menstruation in the controls to day 4 of the cycle in G1 and G2. Peak plasma FSH levels were attained within 6 days in the controls and within 2 or 3 days in both treatment periods. Our data suggest that it is the decrease in plasma E2 rather than inhibin that is the triggering signal for the LFT rise in plasma FSH. The exact roles of inhibin and other gonadal proteins (e.g. activins) in follicular recruitment remain to be determined. PMID- 8345047 TI - Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. AB - Efforts to develop a hormonal contraceptive regimen for men have focused on administration of testosterone (T), alone or together with other agents. Previous regimens have successfully induced azoospermia in only 50-70% of subjects, however. GnRH antagonists, alone or in combination with T, have been shown to induce azoospermia in a very high percentage of nonhuman primates. We tested the hypothesis that the addition of a GnRH antagonist to a high-dose T regimen would lead to a higher percentage of men developing azoospermia than would T alone. We administered the GnRH antagonist, Nal-Glu (100 micrograms/kg.day sc), plus T enanthate, 200 mg im weekly or placebo sc injections daily plus T enanthate, 200 mg im weekly, to separate groups of healthy men for 16-20 weeks. Seven of 10 men who received Nal-Glu plus T and 6 of 9 men who received T alone became azoospermic; gonadotropin levels were suppressed and T levels were increased similarly in both groups. There was a trend toward higher pretreatment gonadotropin levels and lower sperm counts in men who became azoospermic. Weight gain, development of acne, and increases in hematocrit and hemoglobin were similar in the two groups. In the majority of the men, sperm counts returned to the baseline levels within 4-5 months after treatment ended. We conclude that with the dosages of Nal-Glu and T we used in this study, the addition of GnRH antagonist to a high-dose T regimen does not increase the ability of T to suppress spermatogenesis in healthy men. Use of a higher dose of Nal-Glu, a lower dose of T, delaying the start of T replacement until several weeks after Nal-Glu injections are initiated, or prolonged hormonal administration might lead to a combination regimen that will suppress spermatogenesis more fully than does T alone. PMID- 8345048 TI - Tissue specificity and serologic reactivity of an autoantigen associated with autoimmune thyroid disease. AB - A recent report has identified a new autoantigen called D1 that appears to be associated with Graves' ophthalmopathy and is expressed in the thyroid and eye muscle. To better characterize the tissue specificity and disease relevance of this antigen, we evaluated the expression of D1 RNA in various human tissues using a reverse transcriptase polymerase chain reaction assay. These studies indicate a wide tissue distribution of the messenger RNA for this antigen, including the thyroid, eye muscle, parathyroid, spleen, skeletal muscle, and uterus. There were variations in the relative amounts of specific message for D1 in the different tissues, with the uterus, thyroid, and eye muscle having the greatest amount of product per microgram of total RNA. A maltose binding protein D1 fusion protein was expressed in Escherichia coli, purified, and used to assess serologic reactivity to D1 by Western blot. Autoantibodies to this antigen were noted in 19 of 24 (78%) of Hashimoto's disease patients, 26 of 41 (63%) of Graves' disease patients, and in 9 of 17 (53%) of normal controls. Sixty percent of Graves' disease patients with clinical ophthalmopathy had antibodies to D1, as did 63% of Graves' patients without signs or symptoms of clinical ophthalmopathy. There was no correlation between reactivity to D1 and either clinical measures of hyperthyroidism or antibody titers to thyroid peroxidase or thyroglobulin. The presence of autoantibodies to this antigen in patients with Hashimoto's disease, in Graves' disease patients without ophthalmopathy and in normal controls indicate that serologic recognition of this antigen is not restricted to patients with ophthalmopathy. In addition, the expression of messenger RNA for this antigen in multiple types of cells questions the tissue specificity of this autoantigen. PMID- 8345050 TI - Insulin surrogates in insulinoma. AB - Universally accepted criteria for relative hyperinsulinemia have not been established for the diagnosis of insulinoma. Therefore, we sought measures of insulin action which might act as surrogates for insulin measurements and thereby contribute to the assessment of hyperinsulinemia. Since insulin is antilipolytic, antiketogenic, and glycogenic we measured plasma beta-hydroxybutyrate, FFA, and the response of plasma glucose to iv glucagon at the end of the prolonged fast in 40 patients, later confirmed histologically to have insulinoma and 25 normal persons. Plasma beta-hydroxybutyrate and FFA concentrations were significantly lower in the patients with insulinoma (median, range), (0.3, 0.1-2.7 vs. 4.5, 1.2 7.0 mmol, P < 0.0001, and 1.03, 0.17-1.75 vs. 1.79, 1.17-3.12 mmol, P < 0.001, respectively), whereas the responses of plasma glucose to glucagon were significantly greater (3.0, 1.4-5.4 vs. 0.7, 0.0-1.3 mmol, P < 0.001) than in the normals. For patients with insulinoma (20/40) and normal subjects (13/25) with plasma glucose less than or equal to 3.3 mmol and plasma insulin and C-peptide concentrations in the normal overnight fasting range, conditions in which hyperinsulinemia is most difficult to assess, a clear distinction was provided by plasma glucose response to glucagon and plasma beta-hydroxybutyrate but not by plasma FFA, plasma insulin, nor plasma C-peptide. We conclude that plasma glucose response to iv glucagon greater than or equal to 1.4 mmol and plasma beta hydroxybutyrate less than or equal to 2.7 mmol, at the end of the prolonged fast are indicative of hyperinsulinemia of insulinoma when the plasma glucose is less than or equal to 3.3 mmol. In this plasma glucose range these insulin surrogates provide better diagnostic accuracy than plasma insulin and C-peptide. PMID- 8345051 TI - A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. I. Serum growth hormone-binding protein. AB - Previous studies have provided compelling evidence that GH secretion increases transiently during midpuberty in normally growing children. Although it is likely that the increase in GH production serves a primary role in generating the pubertal growth spurt, such a conclusion necessarily assumes that other essential "down-stream" components of the GH axis responsible for mediating the effects of GH remain unchanged. To investigate this concept, we assessed longitudinally another important component of the endogenous GH axis, the serum GH-binding protein (GHBP)/receptor system, in a cohort of 11 normal boys as they matured through normal puberty. At 4-month intervals over 4.0-5.1 yr, 24-h serum GH concentration profiles and serum GHBP activity were evaluated. Serum GHBP levels varied over a more than 12-fold range (40-504 pmol/L) among all subjects. However, the values for individual subjects consistently varied within more narrow limits. The coefficient of variation for values from all subjects was 51% compared to the mean intrasubject coefficient of variation of only 30% (P < 0.05). Although the highest GHBP level (all subjects) was 12.6-fold greater than the lowest, the mean intrasubject range was only 3.1 +/- 0.5-fold (P < 0.05). The overall mean serum GHBP level correlated directly with the overall mean body mass index (r = 0.69; P = 0.018), but correlated inversely with the mean 24-h GH concentration (r = -0.61; P < 0.05). There was no significant increase in the GHBP level during puberty. However, because mean 24-h GH concentrations did increase during midpuberty, the data suggest that an increase in the relative amounts of free vs. bound GH develops during the period of the pubertal growth spurt. These data indicate that serum GHBP levels are regulated in individual children within much more narrow limits than those present in the larger population and do not undergo the dramatic changes during puberty typical of GH secretion and linear growth velocity. As a consequence, alterations may develop in the relative amounts of free vs. bound GH present in serum during the midpubertal years compared to those present during either the prepubertal or postpubertal periods. The majority of the known age-related increase in serum GHBP levels probably occurs before the period of active pubertal development. These findings strengthen further the concept that the midpubertal changes in GH secretion serve a primary role in generating the growth spurt.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345052 TI - Characterization of pulsatile secretion and clearance of plasma cortisol in premature and term neonates using deconvolution analysis. AB - Pulsatile secretion of cortisol (F) has not been documented in the newborn infant. Using repeated blood sampling and deconvolution analysis, we investigated F secretion and elimination dynamics in a group of five premature (gestational age, 24-34 weeks) and five term neonates. These infants had required placement of an umbilical arterial cannula for monitoring respiratory status, but were otherwise clinically stable. Blood samples were obtained at 15-min intervals for a 6-h period. All plasma F determinations were 58 nmol/L (2.1 micrograms/dL) or more, and pulsatile F secretion was observed in all infants. No significant differences were noted between the two groups with regard to 6-h mean plasma F concentration [350 +/- 129 (premature) vs. 277 +/- 54 nmol/L (term)], plasma corticosteroid-binding globulin (14 +/- 0 vs. 13 +/- 1 mg/L), F secretory burst frequency (4 +/- 0 vs. 5 +/- 1 bursts/6 h), mass of F secreted per burst [760 +/- 480 vs. 310 +/- 100 nmol/Lv [Lv, liter of F distribution volume)], F production rate (FPR; 2.7 +/- 1.4 vs. 1.1 +/- 0.2 mumol/Lv.6 h), or plasma F half-life (45 +/- 6 vs. 56 +/- 4 min). However, the premature infants had a significantly longer F secretory burst half-duration (63 +/- 18 vs. 6.7 +/- 4.0 min; P < 0.01) and a significantly lower maximal F secretory rate (9.4 +/- 3.4 vs. 100 +/- 26 nmol/Lv.min; P < 0.02) than the term infants. Body surface area and body weight were inversely correlated with F secretory burst half-duration (r = -0.74 and 0.75, respectively); both were also positively correlated with the maximal F secretory rate (r = 0.66 and 0.72). The two most premature infants had significantly greater mean plasma F and FPR than the other three premature and all of the term infants. Extrapolating to 24 h and correcting for the distribution volume of F and body surface area, we estimate FPR to be approximately 17-24 mumol/m2.24 h (6.6-8.8 mg/m2.24 h) for newborn infants of 34 weeks or more gestational age. These values are consistent with newer estimates of FPR in older children and adults determined using either deconvolution analysis or stable isotope dilution methods. PMID- 8345054 TI - Magnetic resonance imaging of overall and regional body fat, estrogen metabolism, and ovulation of athletes compared to controls. AB - The association of menstrual dysfunction of athletes with changes in body composition has been controversial, because most estimations of body fatness have been indirect. Using magnetic resonance imaging, we quantified the sc and internal fat over a specific volume from the fifth thoracic vertebra to femoral fat in the upper thigh and at 4 other anatomical landmarks of 17 athletes (13 oarswomen and 4 runners) compared to that in 11 nonathletic controls. The magnetic resonance imaging data were also analyzed for the athletes and controls in relation to ovulatory status, which was determined by assay of urinary pregnanediol glucuronide, and in relation to the extent of 2-hydroxylation of estradiol to a nonpotent metabolite, 2-hydroxyestrone, which was evaluated by radiometric analysis. We found that 1) the relative and absolute body fat values of the athletes were significantly less (P < 0.05) than those of the controls overall and at each of the six regional sites, although the body weights of the rowers were significantly heavier than those of the controls, and the runners did not differ from the controls; 2) the ratio of sc fat to internal fat was 80%:20% among both athletes and controls, even though the athletes had significantly less fat; 3) the extent of estradiol 2-hydroxylation was significantly (P = 0.005) inversely related to total fat as a percentage of the total volume and to sc fat as a percentage of the total volume (P = 0.004) overall and at each of the regional fat depots; 4) athletes with menstrual disorders had significantly decreased sc and internal fat overall and at all regional sites compared to controls; and 5) a subgroup of ovulatory rowers had an apparent increase or lack of decrease in internal fat at the level of vertebrae lumbar 4, sacral 1, and sacral 4, compared to controls, whereas their sc fat was decreased at these sites compared to that in controls. Changes in regional fat deposits of both sc and internal fat may be involved in the menstrual dysfunction of the athletes in addition to their decreased overall fatness. The body weight and body mass index of well trained athletes can be a misleading index of body composition. PMID- 8345053 TI - Intracellular glucose metabolism after long term metabolic control with glyburide: improved glucose oxidation with unchanged glycogen synthase activity. AB - To determine whether improved metabolic control with long term glyburide treatment alters intracellular glucose metabolism independent of effects on glucose uptake (GU), we studied eight obese patients with noninsulin-dependent diabetes mellitus before and 7 months after glyburide therapy. Indirect calorimetry and skeletal muscle biopsies were performed in the basal state and during 300 pmol/m2.min insulin infusions, with glucose turnover rates determined by [3-3H]glucose turnover. During the glucose clamps, rates of GU were matched before and after treatment using equivalent hyperinsulinemia and variable levels of hyperglycemia. After glyburide treatment, rates of GU were decreased in the basal state [4.16 +/- 0.57 vs. 3.29 +/- 0.37 mg/kg fat free mass (FFM)/min; P < 0.05], but similar during glucose clamps (11.53 +/- 1.42 vs. 11.93 +/- 1.32 mg/kg FFM.min; P = NS) according to study design. In both the basal state and during glucose clamps after glyburide therapy, rates of glucose oxidative metabolism (Gox) increased by 68-78% [1.21 +/- 0.16 vs. 2.03 +/- 0.31 mg/kg FFM.min (P < 0.05) and 3.13 +/- 0.51 vs. 5.58 +/- 0.55 mg/kg FFM.min (P < 0.05), respectively], and rates of nonoxidative glucose metabolism decreased [2.96 +/- 0.68 vs. 1.25 +/- 0.21 mg/kg FFM.min (P < 0.05) and 8.40 +/- 1.50 to 6.30 +/- 1.40 mg/kg FFM.min (P < 0.01), respectively]. Circulating plasma FFA levels and rates of fat oxidation (Fox) remained unchanged in both the basal state and during clamp studies. Skeletal muscle glycogen synthase (GS) activity, expressed as fractional velocity, was unchanged by glyburide therapy (2.2 +/- 0.8 vs. 2.7 +/- 0.3% in the basal state and 7.3 +/- 1.8 vs. 6.1 +/- 0.9% during clamps; both P = NS). In summary, at both matched (during clamp studies) and unmatched (during basal studies) rates of GU, improved metabolic control with glyburide therapy resulted in marked improvement of Gox independent of the effects on GU. The improvement in Gox was not associated with changes in Fox, circulating FFA, or muscle GS activity. These data indicate that long term metabolic control achieved by glyburide therapy markedly improves Gox, but not skeletal muscle GS activity, in noninsulin-dependent diabetes mellitus independent of GU and Fox. PMID- 8345055 TI - Factors determining glucose tolerance in patients with thalassemia major. AB - To better understand the pathophysiology of glucose intolerance secondary to iron overload in patients with thalassemia major, we performed tolbutamide-modified frequently sampled iv glucose tolerance tests (FSIGTs) in 10 thalassemic patients (6 males and 4 females; 21.7 +/- 1.2 yr old; body mass index, 19.7 +/- 0.6 kg/m2) and 10 healthy controls (5 males and 5 females; 22.4 +/- 1.3 yr; body mass index, 20.6 +/- 0.5 kg/m2). Insulin secretion and action were quantified by application of the minimal model of glucose kinetics and the combined model of insulin and C peptide kinetics to the FSIGT data. The insulin sensitivity index was significantly lower in thalassemia patients [72 +/- 12 min-1(nmol/mL)] compared to controls [158 +/- 21 min-1(nmol/mL); P = 0.0026]. The integrated insulin response during the FSIGT was significantly greater in thalassemia patients than in controls after tolbutamide injection (P = 0.042). The difference in insulin levels was apparently due to reduced hepatic insulin extraction in thalassemia (78 +/- 2% vs. 68 +/- 3%; P = 0.0251). Seven of the 10 thalassemia patients were studied prospectively at 6-month intervals for 6-12 months. Repeated measures analysis of variance indicated that across a 6-month interval, there was a decrease in the total integrated insulin response (P = 0.002), with no change in insulin sensitivity (P = 0.86). In conclusion, patients with thalassemia major have significant insulin resistance, which may be compensated for by an elevated circulating insulin level. The elevated insulin level in response to tolbutamide appears to be due to reduced hepatic extraction of insulin and not to an enhanced insulin secretory response. Over time, patients with thalassemia experience a reduction in their circulating insulin levels. Persistent insulin resistance along with a progressive reduction in circulating insulin levels may lead to glucose intolerance and diabetes mellitus, which have a high prevalence in patients with thalassemia major. PMID- 8345056 TI - Deletion of amino acids Asp487-Ser488-Phe489 in human cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency. AB - 17 alpha-Hydroxylase deficiency blocks the biosynthesis of cortisol and sex steroids, resulting in mineralocorticoid excess, hypertension, sexual infantilism, and female phenotype in both genetic sexes. The disease is caused by mutations in the gene encoding cytochrome P450c17, which is the single enzyme that mediates both 17 alpha-hydroxylase and 17,20-lyase activities. We report a 14-yr-old patient from Thailand with a classical clinical presentation of this rare disorder. Analysis of her P450c17 gene by polymerase chain reaction amplification and sequencing showed a nine-base deletion, eliminating codons 487 489 (Asp-Ser-Phe) near the carboxy-terminus of P450c17. This deletion creates a BclI site in the mutant DNA, permitting accurate demonstration that the patient was homozygous for this lesion, whereas one parent and two siblings were heterozygous. By use of site-directed mutagenesis, we created a vector that could express this mutated form of P450c17 when transfected into non-steroidogenic COS 1 cells. Such transfected cells produced immunodetectable P450c17 protein, but had no 17 alpha-hydroxylase or 17,20-lyase activity, whereas cells similarly transfected with a vector expressing normal human P450c17 could 17 alpha hydroxylate either pregnenolone or progesterone and convert 17 alpha hydroxypregnenolone to dehydroepiandrosterone, showing the presence of both activities. This is the first report of the molecular genetic basis of 17 alpha hydroxylase deficiency in a Southeast Asian patient. PMID- 8345057 TI - Estradiol stimulates cortisol production by adrenal cells in estrogen-dependent primary adrenocortical nodular dysplasia. AB - Adrenal glands from a patient with ACTH-independent Cushing's syndrome, whose symptoms worsened during pregnancy and oral contraceptive use, were cultured in different concentrations of estradiol. Estradiol stimulated cortisol secretion in a dose-response manner in the absence of ACTH. Since immunoglobulins G from this patient did not stimulate corticosterone production in a mouse adrenal bioassay, an adrenal-stimulating immunoglobulin is unlikely to be the cause of adrenal hyperfunction in this case. This is the first description of estradiol stimulation of cortisol production by cultured adrenal cells in ACTH-independent Cushing's syndrome. PMID- 8345058 TI - Glomerular hyperfiltration in insulin-dependent diabetes mellitus is correlated with enhanced growth hormone secretion. AB - Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability. PMID- 8345059 TI - Do heat shock proteins play a role in Graves' disease? Heat shock protein specific T-cells from Graves' disease thyroids do not recognize thyroid epithelial cells. AB - Thyroid-derived T-cells from patients with Graves' disease were analyzed for their reactivity to recombinant heat shock proteins (hsp) and autologous thyroid epithelial cells (TEC). Five of six uncloned T-cell lines responded to stimulation with recombinant mycobacterial 71-kilodalton (kDa) hsp and cross reacted with the corresponding amoebial and human proteins. Only one line reacted with recombinant 65-kDa hsp. Thyroid-derived T-cell lines also showed a proliferative response to TEC, which could be increased in four of the lines, when hsp expression was induced in thyroid cells by heat stress before the initiation of coculture. Clonal specificity analysis of thyroid-derived T-cell clones, however, demonstrated that distinct T-cells were responsible for the recognition of recombinant hsp and TEC. None of the clones responsive to recombinant hsp recognized TEC, whereas TEC-responsive clones did not react with recombinant hsp. Interestingly, the response of the majority of TEC-reactive clones could be dramatically increased when heat-shocked TEC were used as stimulator cells. These results suggest that T-cells specific for hsp of the 70- or 60-kDa families do not recognize TEC in the autoimmune thyroid gland. Heat shock-inducible proteins may, however, still play a role in the autoimmune process by facilitating the presentation of thyroid-specific autoantigen(s) to autoreactive T-cells. PMID- 8345060 TI - Inhibin and activin in human fetal membranes: evidence for a local effect on prostaglandin release. AB - Trophoblast and fetal membranes (amnion and chorion) are the tissues forming the anatomical/functional interface between the mother and the fetus. The aim of the present study was to evaluate the presence and a possible effect of inhibin and activin in human amnion and chorion. The expression of inhibin/activin alpha, beta A, and beta B subunit messenger RNA (mRNA) and the localization of immunoreactive material were evaluated in amnion and chorion collected at term pregnancy by a Northern blot analysis and by immunohistochemistry. Amnion cells expressed the mRNA of the three inhibin/activin subunits, with the beta B message the most abundantly expressed. The epithelial layer of the amnion showed an intense fluorescent staining of beta B inhibin/activin subunit, and positive signals were also observed for the alpha and beta A subunits. Inhibin/activin alpha and beta A subunit mRNAs were found highly expressed in chorion. The cytotrophoblast of the chorion showed a positive staining for the three inhibin/activin subunit antisera. The addition of activin A increased the release of prostaglandin E2 from human amnion-derived cultured cells. The effect was dose and time dependent. Inhibin A did not induce significant changes of prostaglandin E2 release from amnion cells. The present results show that amnion and chorion produce inhibin and activin subunits and that activin stimulates the release of prostaglandin E2 from cultured amnion cells, suggesting a possible role of inhibin and activin in fetal membranes. PMID- 8345061 TI - Localization of interleukin-1 type I receptor and interleukin-1 beta in human endometrium throughout the menstrual cycle. AB - Previous studies in the human suggest that the interleukin-1 (IL-1) system, may be an important paracrine/autocrine mediator in local intercellular interaction in endometrial tissue. In this study we have determined that IL-1 receptor type I (IL-1R tI) is expressed at the messenger RNA (mRNA) and protein levels in glandular cells and its ligand, IL-1 beta has been localized by immunohistochemical methods in endothelial cells and isolated stromal cells in the human endometrium throughout the menstrual cycle. IL-1R tI mRNA was detected in glandular epithelium using both specific complementary DNA and complementary RNA 32P-labeled probes. Human glandular epithelium contains a 5.1-kilobase mRNA transcript throughout the complete menstrual cycle. Quantitative densitometric analysis of slot blot hybridization signals shows an increase of IL-1R tI mRNA in both early and mid-late secretory phases in comparison with the proliferative phase (P < 0.05). IL-1R tI protein was localized in endometrial glandular epithelial cells using both indirect immunofluorescence and avidin-biotin peroxidase methods. However, more intense staining for IL-1R tI was observed in lumenal epithelial cells compared with the staining present deep in the endometrial glands. Using the same methods, IL-1 beta was detected in endothelial cells of spiral vessels and isolated stromal cells throughout the menstrual cycle, and an increased staining from proliferative to secretory phase was observed. The detection of IL-1R tI in the human endometrial epithelium and its ligand, IL-1 beta, in isolated stromal cells and endothelial cells, is another example of possible communication between the immune and reproductive systems with special relevance to human implantation. PMID- 8345062 TI - Prostaglandins stimulate the secretion of inhibin from human placental cells. AB - In this study, the effects of prostaglandins (PGs) on inhibin secretion were investigated in primary culture of human placental cells. Isolated trophoblast cells were cultured for 2-5 days with PGE1, PGE2, 6-keto-PGF1 alpha, PGF2 alpha, and thromboxane B2. Inhibin levels in the culture medium were measured by immunoenzymatic assay. PGs significantly stimulated inhibin secretion in the cell culture. The addition of PGs (1 nM to 10 microM) to the culture resulted in dose dependent increases in inhibin levels in the medium. At a dose of 10 microM, inhibin levels in the medium were increased by 35.2-172.5% compared to the control value. Compared with the efficacies of these PGs, PGE2 and PGF2 alpha enhanced inhibin secretion more potently than other tested PGs. A close correlation between the effects of PGs and the number of trophoblasts seeded in the culture was observed, with an optimal response of the cells to PGs at 1.0-2.0 x 10(6) cells/well. Time-course studies showed that a significant increment in inhibin levels in the PG-treated culture occurred after 48-120 h, but not during the first 24 h, of the culture, indicating a possible involvement of PGs in inhibin biosynthesis in the cells. Epidermal growth factor (EGF) could enhance PG stimulated inhibin releases in the cell culture. Treatment with EGF (100 ng/mL) increased inhibin in the medium by 83.3% (ED50) in the presence of PGE2 or by 70.3% (ED50) in the presence of PGF2 alpha compared to the control values. The addition of 8-bromo-cAMP (100 microM) and cholera toxin (1000 ng/mL) to the culture also enhanced basal and PG-induced inhibin secretion, but the addition of the 4-bromo-calcium ionophore A23187 (1 microM) did not alter inhibin releases, suggesting that the stimulatory effects of PGs on inhibin secretion in placental cells may be mediated through the cAMP pathway. In the cell cultures treated with PGE and PGF2 alpha, there was no change in cell growth or intracellular DNA content, as measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assay and DNA determination with fluorescence spectrophotometry. Morphological studies showed that PGE2 alpha (1 microM), alone or combined with EGF (100 ng/mL), significantly accelerated the process of differentiation from cytotrophoblasts to syncytiotrophoblasts, indicating that the actions of PGs may be related to their effects on syncytial transformation, rather than cellular proliferation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345063 TI - Circulating calcitonin levels in healthy children and subjects with congenital hypothyroidism from birth to adolescence. AB - Using an extraction-concentration technique of circulating calcitonin (exCT) that permits a sensitive and specific assessment of circulating CT monomer levels, we measured exCT levels in 115 healthy children (59 girls and 56 boys), aged 0-16 yr, and 25 patients (15 girls and 10 boys), aged 2 months to 22 yr, with congenital hypothyroidism (CH), a condition characterized by a marked CT deficiency in adults. We found a significant negative correlation between CT levels and age in healthy children (girls, r = -0.83; boys, r = -0.63; P < 0.001). There was a 5-fold decrease in CT levels from the neonatal period to adolescence. The fall in CT levels was particularly marked in early infancy (e.g. for the age category 1 day to 1 yr, 19.0 +/- 1.9 vs. 7.3 +/- 1.2 ng/L for the group 1-5 yr, P < 0.01), but less pronounced thereafter (for the group 5-10 yr, 4.7 +/- 0.8 ng/L; P < 0.001 vs. the group 1 day to 1 yr). The well established sex difference in CT levels in adults was significant only for the age category above 10 yr (2.7 +/- 0.4 ng/L for girls vs. 4.5 +/- 0.7 ng/L for boys, P < 0.05). In patients with CH, the mean exCT level was 2.0 +/- 0.3 ng/L under 3 yr of age (n = 9), whereas all CT values were undetectable after the age of 3 yr, which could contribute to the lower bone mass of adult CH patients. CT values were normal in 3 children with metabolic goiter. In healthy children, our results demonstrate the existence of an age-related decrease in circulating CT levels, which was particularly marked in infancy. The sex difference in CT levels progressively appeared in childhood, but was significant only after 10 yr of age. Such changes in CT levels could be important for neonatal calcium metabolism and contribute to the lower bone mass in females. PMID- 8345064 TI - Search for a biological clock in the ontogeny of puberty. PMID- 8345065 TI - The production of placental protein 14 and interleukin 6 by human endometrial cells in culture. AB - Epithelial and stromal cells prepared from endometrium taken at different times in the menstrual cycle were grown in primary culture and the production of placental protein 14 (PP14) and interleukin-6 (IL6) measured. Only the epithelial cells produced PP14. Epithelial cells from endometrium in the late secretory phase produced significantly greater amounts of PP14 (42 +/- 5.8 ng/24 h) compared with that produced by cells from early secretory and proliferative endometrium (16 +/- 1.7 and 11 +/- 1.9 ng/24 h respectively). PP14 production by cells from endometrium at all stages in the cycle was increased by progesterone, or progesterone and oestradiol together, while oestradiol alone had no effect on PP14 production. The greatest stimulation was seen during the early secretory phase when stimulated levels of PP14 reached those obtained during the late secretory phase. IL6 production by epithelial cells also varied depending on the phase of the menstrual cycle. More IL6 was produced by the cells prepared from the endometrium in the proliferative phase (10.9 +/- 0.56 ng/24 h) compared with that produced by cells from early and late secretory endometrium (2.5 +/- 0.19 and 1.45 +/- 0.09 ng/24 h respectively). Addition of steroids to the media stimulated the production of IL6 by cells from proliferative and early secretory endometrium but decreased IL6 production from cells in the late secretory phase. IL6 was also produced by stromal cells but could only be detected in supernatants of cells prepared from late secretory endometrium, and the amounts produced (0.8 +/- 0.09 ng/24 h) were less than that produced by epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345066 TI - Transvaginal sonographic evaluation of endometrial growth and texture in spontaneous ovulatory cycles--a descriptive study. AB - Repeated transvaginal ultrasonographic examinations were performed during spontaneous ovulatory cycles to follow the texture and growth pattern of the endometrium in 23 healthy volunteers. The serum concentrations of oestradiol, progesterone and luteinizing hormone (LH) were measured regularly. The day of the LH peak was designated as day 0. On ultrasound only one thin echogenic line was seen from menstruation to day -7. From days -6 to -1 a change from one to three thin lines was observed together with an increasing hypoechogenic texture between the lines. These changes corresponded to the increasing serum concentration of oestradiol and increasing thickness of the endometrium. At ovulation there was maximum hypoechogenic texture between the lines which had become thicker. At ovulation the endometrium had a mean thickness (both layers) of 12 mm. From days +1 to +6 an increasing blurring of the three lines became apparent and the previously hypoechogenic layers gradually displayed a more echogenic texture. From day +7 to menstruation the lines were indistinguishable due to the appearance of a general hyperechogenic texture of the endometrium. In the luteal phase the growth of the endometrium plateaued. The results indicate that ultrasound assessment of endometrial growth and texture may be an important tool to evaluate normal ovulatory endometrial development. It can also be useful in monitoring stimulated cycles in different treatment modalities of assisted reproduction. PMID- 8345067 TI - Ovarian stimulation with buserelin/HMG/HCG: prospective randomized study of short versus long protocol. AB - The combined administration of the gonadotrophin-releasing hormone (GnRH) agonist buserelin and human menopausal gonadotrophin (HMG) was evaluated in 527 cycles (428 patients) of an assisted reproduction programme. All women were randomly allocated according to the ovulation induction protocol into two groups: group I (short protocol; 318 cycles) was given buserelin (1 mg/day) intranasally from cycle day 1 and HMG (2 ampoules/day) from day 3 until human chorionic gonadotrophin (HCG) administration: group II (long protocol; 209 cycles) was given buserelin (1 mg/day) intranasally from cycle day 1 for at least 14 days and then 2 ampoules HMG/day were added, increasing progressively according to the ovarian response. The number (mean +/- SEM) of follicles developed was higher in group II than in group I (9.1 +/- 0.4 versus 7.7 +/- 0.3, respectively; P < 0.05). More oocytes were retrieved in group II (8.4 +/- 0.5) than in group I (6.5 +/- 0.3) (P < 0.001), as well as more embryos (6.3 +/- 0.5 and 4.0 +/- 0.3, respectively; P < 0.001). Moreover, in group II there was a better correlation between oestradiol and the total follicular volume (r = 0.5391) on cycle day 0 compared with group I (r = 0.458), while oestradiol values were similar between the two groups. No differences were observed in the cancellation rate, fertilization rate and maturity of the oocytes between the two groups. The pregnancy rate per transfer was slightly better in group II (25.8%) than in group I (19.4%), but this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345068 TI - Pharmaco-dynamics of human menopausal gonadotrophin (HMG) and follicle stimulating hormone (FSH). The importance of the FSH concentration in initiating follicular growth in polycystic ovary-like disease. AB - Using a randomized double-blind cross-over design, the pharmaco-dynamic and pharmaco-kinetic properties of 'pure' follicle-stimulating hormone (FSH) (Metrodin) and human menopausal gonadotrophin (HMG) (Pergonal) were studied in 24 women with polycystic ovary-like disease (PCOD) during induction of ovulation. Fifty-six cycles were stimulated with FSH and 60 cycles with HMG, according to a standard protocol. Gonadotrophins were administered i.v. in a pulsatile fashion using pulse frequencies of either 30 or 120 min. The cycles stimulated with either 30 or 120 min pulse intervals showed no differences among themselves. During the stimulation phase, the FSH and HMG stimulated cycles showed equal and dose dependent FSH concentrations (mean +/- SD). The luteinizing hormone (LH) concentrations (mean +/- SD) were also equal but unchanged compared to the mean basal concentration. The LH, FSH, total urinary oestrogen excretion, and testosterone profiles (mean +/- SD) obtained from cycle days -10 to 0 as well as the pregnanediol profiles obtained from cycle days 0 to +14 showed no differences either. The occurrence of an endogenous preovulatory LH surge was significantly more frequent in the cycles stimulated with a pulse interval of 30 min compared to the cycles stimulated with a pulse interval of 120 min. The addition of LH as provided in HMG did not influence the FSH threshold concentration above which initiation of follicular growth occurred, since no differences were found in the FSH 'stable' concentrations between FSH and HMG stimulated cycles. However, intra and inter-individual variation in the FSH 'stable' concentration at which follicular growth was initiated became obvious.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345069 TI - Effects of gonadotrophin surge-attenuating factor on the two pools of gonadotrophin-releasing hormone-induced luteinizing hormone secretion in vitro. AB - In order to study the in-vitro mechanism of action of gonadotrophin surge attenuating factor (GnSAF), ovine pituitary monolayers were incubated for 48 h either with steroid-free follicular fluid from women in whom ovulation had been induced or oestradiol or progesterone. Monolayers were also incubated with 10-30 and > 30 kDa follicular fluid fractions. The effect of these preparations on gonadotrophin-releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion was then determined by incubation with GnRH for between 15 and 240 min. Incubation with steroid-free follicular fluid resulted in the significant attenuation of both the acutely releasable LH pool (LH 54.3 +/- 3.0% of control secretion at 15 min of GnRH incubation) and the reserve LH pool (LH 36.8 +/- 1.6% of control secretion at 240 min GnRH incubation). The 10-30 kDa follicular fluid fraction had similar effects while the > 30 kDa follicular fluid fraction significantly stimulated GnRH-induced LH secretion, with concentrations up to 134.0 +/- 8.6% of controls. Oestradiol or progesterone at doses of 1000 nmol/l/well did not significantly reduce any aspect of GnRH-induced LH secretion (never < 95.1 +/- 15.1% of controls). These results demonstrate that GnSAF markedly attenuates both the acutely releasable and reserve pools of GnRH-induced LH secretion. Inhibin, oestradiol and progesterone are not responsible for the marked attenuation of either the initial or reserve pools of GnRH-induced LH secretion. PMID- 8345070 TI - Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage. AB - Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone (LH) which has been implicated in the aetiology of early pregnancy loss. Although 82% of women with recurrent early loss have polycystic ovaries on ultrasound imaging, random serum LH concentrations are normal. In the present study, we have obtained further information from serial samples concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women. Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated; 81% of them and one of ten control subjects had polycystic ovaries. Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone (FSH) levels were similar in both groups. Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge; one control subject had a premature LH surge. Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group, the difference in LH being greatest in the early luteal phase. Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion. These data demonstrate abnormalities in LH secretion in 81% of women with recurrent fetal loss. Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly, or indirectly by causing an elevation in testosterone and oestrogen levels. PMID- 8345071 TI - Another look at co-treatment with growth hormone and human menopausal gonadotrophins in poor ovarian responders. AB - The objective of this study was to evaluate whether a combined human growth hormone (HGH) and human menopausal gonadotrophin (HMG) treatment can improve ovulation induction in poor ovarian responders. Ten patients aged 28-43 years and requiring > 25 ampoules of HMG for ovulation were admitted to the study. Pituitary growth hormone reserve was evaluated by clonidine stimulation and insulin tolerance tests before commencement of treatment. The patients underwent one treatment cycle with D-tryptophan-6-luteinizing hormone-releasing hormone (D Trp6-LHRH) and HMG and another cycle with D-Trp6-LHRH, HMG and HGH. Serum HGH, insulin-like growth factor (IGF)-I and oestradiol were measured throughout the two treatment cycles and follicular maturation was assessed by ultrasonographic studies. All patients tested showed no elevation of their serum HGH concentration during a clonidine test, but showed an adequate response during insulin tolerance tests. No significant difference was found in the number of HMG ampoules, duration of treatment, number of leading follicles, and serum oestradiol concentration between the two treatment cycles. Co-treatment with HGH and HMG did not improve ovarian performance in poor ovarian responders. No correlation was found between the results of HGH pituitary function tests and the ovarian response to gonadotrophins. PMID- 8345072 TI - Endocrine composition of follicular fluid comparing human chorionic gonadotrophin to a gonadotrophin-releasing hormone agonist for ovulation induction. AB - Concentrations of inhibin, oestradiol and progesterone were determined in pre ovulatory follicular fluid from 16 women undergoing in-vitro fertilization and embryo transfer treatment. A prospective randomized design was used such that ovulation was induced in eight women with human chorionic gonadotrophin (HCG) (9000 IU), and in eight women with an endogenous surge of luteinizing hormone (LH) and follicle stimulating hormone (FSH) caused by a single injection of gonadotrophin-releasing hormone agonist (GnRHa). Inhibin was measured by an enzyme-linked immunosorbent assay, and oestradiol and progesterone were measured by radio-immunoassay. Concentrations of inhibin and progesterone are significantly higher in follicular fluids collected after ovulation induction with HCG compared with ovulation induction with GnRHa (P < 0.001, P < 0.02, respectively). Concentrations of oestradiol were similar in the two groups. This study shows that the method by which ovulation is triggered significantly affects the micro-environment of the oocyte just prior to ovulation. The results indicate that HCG causes a prolonged luteotrophic effect well before ovulation, compared to an endogenous surge of gonadotrophins caused by GnRHa, and suggest that follicular maturation with an endogenous surge of gonadotrophins may be closer to the natural cycle than those cycles in which HCG is administered for ovulation induction. In addition, this study shows that the concentrations of inhibin and progesterone in follicular fluid may be valuable parameters in assessing the midcycle LH surge requirements for induction of ovulation. PMID- 8345073 TI - Morphological assessment of polycystic ovary using transvaginal ultrasound. AB - A total of 104 patients with bilateral polycystic ovaries (PCO) diagnosed by transvaginal ultrasound were classified into four groups (A < 5 cysts, B 5-10 cysts, C > 10 cysts located under ovarian capsule, D numerous cysts distributed all over the ovary) according to the number of microcysts. Ovarian volume, clinical features (menstrual disturbance, obesity and hirsutism), endocrine levels [luteinizing hormone (LH), LH/follicle stimulating hormone ratio, testosterone, androstenedione and dehydroepiandrosterone-sulphate] and response to clomiphene were compared for each group and 17 control subjects with normal ovulatory cycles. Ovarian volume in PCO subjects was significantly larger than that in control subjects. As the number of microcysts increased, the ovarian volume enlarged and the endocrine abnormality worsened. All endocrine parameters in PCO subjects with menstrual disturbances were significantly higher than those in PCO subjects without menstrual disturbances and controls. In PCO subjects without menstrual disturbances only androstenedione was significantly higher than in controls. Among PCO subjects, the frequency of menstrual disturbances, the percentage of response to clomiphene and the pregnancy rate in groups C and D were significantly higher than in groups A and B. Therefore, screening the ovaries in infertile patients by means of transvaginal ultrasound and subsequent assessment of morphology in PCO may suggest endocrine abnormality and help in selecting the proper treatment. PMID- 8345074 TI - Effect of insulin on human chorionic gonadotrophin secretion by placental explants. AB - The effect of physiological concentrations of insulin (5-50 microU/ml) was tested on human chorionic gonadotrophin (HCG) secretion by first trimester (7-9 weeks) and term placental explants using both static and dynamic culture models. In static cultures, insulin exerted a significant biphasic inhibitory effect (80% at 5 microU/ml and 40% at 50 microU/ml) on HCG secretion by placental explants. At approximate fasting plasma levels, 25 microU/ml insulin added to superfused explants for > or = 8 min also had a rapid inhibitory effect. A delayed inhibitory effect on HCG pulsatility was also observed using 25 microU/ml insulin, with a 2-fold decrease in HCG pulse amplitude and a 4-fold decrease in the area under the curve following overnight pre-incubation (P < 0.01). Insulin had no effect in static cultures at term. The effect of insulin-like growth factor (IGF-I) and fibroblast growth factor (bFGF) on HCG secretion in static cultures was not statistically significant. In conclusion, physiological concentrations of insulin inhibit HCG secretion in first trimester placenta in vitro. This effect is gestational age dependent and specific since it is not mimicked by IGF-I or bFGF. Thus, insulin may be an important modulator of trophoblastic HCG secretion during early pregnancy. PMID- 8345075 TI - First established pregnancy and birth after ovarian stimulation with recombinant human follicle stimulating hormone (Org 32489). AB - This case report describes the first established pregnancy and birth after ovarian stimulation with Org 32489, pure recombinant human follicle stimulating hormone (recFSH, Organon International). A patient with tubal infertility participated in an open efficacy study of recFSH evaluating the efficacy of combined gonadotrophin-releasing hormone (GnRH)-agonist/recFSH treatment in women undergoing in-vitro fertilization (IVF) and embryo transfer. Ovarian stimulation was induced by recFSH in association with buserelin (Suprecur, 4 x 150 micrograms/day) using a short protocol. After 9 days of recFSH treatment (75 IU/day), six pre-ovulatory follicles (> or = 15 mm) were observed and 10,000 IU human chorionic gonadotrophin were administered. Nine mature oocytes were retrieved by oocyte puncture and after IVF, three embryos were replaced in the uterus. A viable singleton intra-uterine pregnancy was revealed at a gestational age of 7 weeks. The pregnancy progressed normally and ended with a vaginal delivery at a gestational age of 39.5 weeks. A healthy girl was born and paediatric examination did not demonstrate any abnormality. PMID- 8345076 TI - Early luteal phase treatment with mifepristone (RU 486) for fertility regulation. AB - Mifepristone (RU 486) is an antiprogestin which interacts with progesterone at the receptor level. Administration of mifepristone immediately after ovulation does not upset the menstrual cycle. However, the maturation and function of the endometrium is inhibited and uterine contractility is changed. To test if these effects are sufficient to prevent implantation, 21 women agreed to use one single treatment with 200 mg mifepristone on day luteinizing hormone (LH) + 2 monthly as their only contraceptive method. The women were treated for 1-12 months. The time of the LH peak was determined in the urine by the women themselves using a rapid LH test (Ovu-quick, Organon). The overall number of cycles studied was 169. In 12 cycles the women were unable to detect the LH peak. In these cycles no treatment was given and the women advised to use barrier methods during the time to menstruation. The remaining 157 cycles with a detectable LH peak were all ovulatory based on plasma progesterone measurement. One pregnancy occurred. On the basis of the time of the LH peak, it was retrospectively calculated that in 124 cycles at least one act of intercourse occurred during the period 3 days before to 1 day after ovulation. The probability of pregnancy in this period of the menstrual cycle is thus 0.008. The women did not complain of any treatment related side-effects apart from slight bleeding for 2-3 days starting a few days after the day of treatment in 35% of the cycles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345077 TI - Psychological considerations of anonymous oocyte donation. AB - This study involved 50 patients interviewed in conversations with a psychologist. It was found that it was possible to characterize the kind of couples using assisted reproductive techniques in terms of diagnostic and psychological profile. Other observations included the repercussions of this action on the couples' stability in case of failure or success, the desire for children and the plans concerning them, the secrecy theme and questions arising from the practice of anonymous or non-anonymous oocyte donation. The relationship between recipients and donors, as well as the specific relationship between couples and their consultants, were also examined. It is concluded that the problems encountered differ according to the infertility diagnosis. Donor anonymity allows oocyte recipients to impose their own identity patterns onto the future child and to introduce him/her in an unbiased way to their own lives. Artificial techniques to assist in the conception of a child do not appear to interfere with the couple's relationship and their desire for a child, which remains constant for each member of the couple. PMID- 8345078 TI - Male infertility and donor insemination: couples' decisions, reactions and counselling needs. AB - This paper reports findings of a postal survey of 205 couples belonging to the National Association for the Childless, whose infertility had been attributed to the male partner. Spontaneous resolution was seldom reported, but 36 couples had become parents by donor insemination (DI) and 28 through adoption. Almost a third of respondents had managed to resolve their childlessness. Although reasons for rejecting DI or preferring other options were offered by 60 couples, 125 had taken active steps towards it. Most of the 80 couples who had been counselled had found this helpful. Regardless of counselling, of the 76 couples who had considered whether or not to tell their children of their mode of conception, 56 (74%) stated that they had no intention of doing so. Quantitative indices from two self-report scales confirm that male infertility is commonly a source of distress, especially for the female partner. However, the data also suggest that this is not necessarily associated with chronic marital discord. Couples who had already decided for or against DI reported less distress than others. The need for mutual support may well be enhanced until the couple's quest for a child has been either achieved or abandoned. PMID- 8345079 TI - Drop-out behaviour and fertility table analysis of pregnancy rates. AB - The life table analysis of infertility study data uses information from patients who drop out and are lost to follow-up. The fact that drop-out patients were not pregnant when last seen has been taken to be useful information that has been entered into the calculation of cumulative pregnancy rates for the population as a whole. However, drop-out patients who subsequently achieve pregnancy have motivations to return to their physician for follow-up, while those who do not become pregnant usually remain lost to follow-up. This can result in a systematic error toward reporting an excess of pregnancies, raising the apparent fecundity rates and plateau values. This study was undertaken to investigate the potential magnitude of these errors. Computer simulations of hypothetical infertility treatments using large cohorts (n = 32 000) were undertaken. Varying assumptions were made regarding post-treatment monthly fecundity rates, 'cure rates', drop out rates and the percentage of pregnant drop-outs who would return to their physician after achieving pregnancy. Using a range of clinically reasonable assumptions, very large deviations from ideal behaviour were noted in the direction of elevated cumulative pregnancy rates. The non-ideal behaviour was most apparent with lower fecundity rates, lower 'cure rates', higher drop-out rates and higher pregnant drop-out return rates. A change in the method of data collection to minimize the impact of this bias in infertility studies is proposed. This method of active data collection is a departure from that used in classical life table studies and therefore the method is titled the 'fertility table method' in order to avoid confusion. PMID- 8345080 TI - Fallopian tube sperm perfusion (FSP) versus intra-uterine insemination (IUI) in the treatment of unexplained infertility: a prospective randomized study. AB - Prospective randomization of 60 couples with unexplained infertility was performed for treatment either with intrauterine insemination (IUI), using a volume of 0.5 ml of the inseminate, or Fallopian tube sperm perfusion (FSP), using a volume of 4 ml of inseminate. The protocols for ovarian stimulation and induction of ovulation were the same in the two groups. The two groups were similar concerning age of the female at the start of treatment and the number of follicles > 15 mm diameter, the serum oestradiol concentrations and the endometrial thickness on the day of human chorionic gonadotrophin (HCG) administration. The mean (+/- SD) number of motile spermatozoa inseminated was significantly higher in the FSP group than in the IUI group (52 +/- 5 x 10(6) and 28 +/- 3 x 10(6) respectively). In the FSP group, 30 women were given a total of 52 treatment cycles; 14 clinical pregnancies occurred in this group, giving a pregnancy rate of 26.9% per cycle and 46.7% per woman. In the IUI group, 28 women were given a total of 51 treatment cycles; five clinical pregnancies occurred, giving a pregnancy rate of 9.8% per cycle and 17.9% per woman. The pregnancy rates per cycle and per woman in the FSP group were significantly higher than in the IUI group (P < 0.05, chi-square test). This study indicates that in the treatment of couples with unexplained infertility, Fallopian tube sperm perfusion (FSP) is more successful than intra-uterine insemination (IUI). PMID- 8345081 TI - Assessment of polyploidy in human morulae and blastocysts using co-culture and fluorescent in-situ hybridization. AB - Fluorescence in-situ hybridization with DNA probes for X, Y and no. 18 chromosomes was used to analyse human morulae (n = 13) and blastocysts (n = 41), obtained after co-culture on Vero cells. On the basis of the number of hybridization signals, the proportion of embryos with more than five polyploid cells was 30.8% for morulae and 29.3% for blastocysts. These values are similar to those for mixoploidy (mosaicism of diploid and polyploid cells) observed in blastocysts of animal species. The results were confirmed by scanning electron microscopy, which showed a wide variation in the size of blastocyst nuclei, and by classical cytogenetic analysis. Mixoploidy seems to be a normal feature in preimplantation embryos and to occur very early in human embryo development. This lays open to doubt the preimplantation diagnosis of genetic errors at these stages, since results obtained from single cell analysis may not be representative of the whole embryo. PMID- 8345082 TI - Immediate rearrangements of human sperm chromosomes following in-vivo irradiation. AB - The short-term effects of radiotherapy on sperm chromosomes was evaluated in two Hodgkin patients. Sperm cytogenetics were analysed by using human-hamster cross fertilization. Immediately after irradiation, most sperm metaphases from the first patient exhibited multiple rearrangements, whereas in the second one, the incidence of such abnormalities was only slightly increased. Multi-fragmented chromosomes and structural aberrations of the chromatid-type were observed, suggesting a specific immediate response. PMID- 8345083 TI - Sub-zonal insemination for extreme male factor infertility. AB - When in-vitro fertilization (IVF) is used for severe male infertility, the zona pellucida constitutes a major barrier to sperm-oocyte interaction, a barrier that may, in principle, be overcome by micro-injecting one or more spermatozoa into the sub-zonal perivitelline space ('sub-zonal insemination' or SZI). We have defined suitable patients for SZI as having 'extreme' male factor in that they have either shown a failure of fertilization in previous IVF cycles or had < 50 000 motile spermatozoa recoverable after semen preparation. (This is distinct from those with only 'severe' male factor in whom sufficient (> 50 000) motile spermatozoa could be recovered from a semen preparation.) A total of 213 SZI cycles were performed at Sydney IVF in the 4 year period September 1988 to September 1992, for extreme male factor patients with previous IVF failures or extremely low sperm numbers for whom SZI was the first option (about two-thirds and one-third of cases respectively). A total of 138 embryo transfers are reported, producing 20 clinical pregnancies after performing SZI on 1899 oocytes. One patient miscarried at 12 weeks gestation and there have been nine normal deliveries (so far) of 10 healthy infants. The first delivery was in February 1990. One pregnancy was achieved in the only patient in whom spermatozoa were obtained by epididymal aspiration, and transfer of three cryopreserved embryos in another patient resulted in a singleton pregnancy. Of the 492 oocytes fertilized, 282 had two pronuclei (57.3%) and normal embryos were transferred in 138/213 (64.8%) treatment cycles, giving an overall pregnancy rate of 14.5% per embryo transfer or 9.4% per cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345085 TI - Growth hormone status in patients with maturation arrest of spermatogenesis. AB - The growth hormone levels of 11 azoospermic patients with histological evidence of maturation arrest of unknown aetiology were studied using the clonidine test. The results were compared with the results from clonidine tests on 10 healthy fertile men and on a group of patients with severe oligozoospermia of various aetiologies. The results demonstrated that 10 patients (91%) in the azoospermic group had non-reactive, pathological responses while none of the control group had a pathological response. Of the severe oligozoospermic group, 82% had normal reactive clonidine tests (P < 0.005). We suggest that growth hormone deficiency may be associated with maturation arrest, and the possibility of treatment with growth hormone should be considered. PMID- 8345084 TI - Efficacy of the sperm survival test for the prediction of oocyte fertilization in culture. AB - The present study was carried out to investigate the predictive value of the sperm survival test (SST) with respect to the fertilization of oocytes in culture. In general, our laboratory uses a total of 50,000-150,000 motile spermatozoa to inseminate each oocyte. The remaining material is evaluated for motility before and after 24 h of incubation at 37 degrees C in a 5% CO2 atmosphere. A total of 250 oocytes from 50 cases (mean +/- SD, 5.0 +/- 2.4 oocytes per retrieval) were inseminated and the final rate of cleaved embryos obtained was 52.5%. The SST (%) was considered normal when the ratio (final density of progressing spermatozoa after 24 h x 100/initial density of progressing spermatozoa) was 50% or more. Any other result was considered abnormal. Cases presenting one or more cleaved embryos (n = 40) were separated from those in which no embryo formation occurred (n = 10) and the results were compared in terms of the respective sperm survival rates over a period of 24 h: normal SST (one or more cleaved embryos, 37; none, five), abnormal SST (one or more cleaved embryos, three; none, five). The specificity of the SST was 0.92 and sensitivity 0.50, the predictive value of the abnormal test was 0.62 and the predictive value of the normal test 0.88. The efficacy of the test was estimated at 0.71, which was better than the conventional parameters of sperm analysis. A receiver-operating characteristics curve for SST confirmed that the test can be useful for the prediction of fertilizability of oocytes in the laboratory. PMID- 8345086 TI - Effect of clomiphene citrate on sperm cell function. AB - Experiments were performed to determine time and dose-dependent effects of clomiphene citrate on the function of fertile donor spermatozoa. The percentages of acrosome-reacted, motile and live spermatozoa were assessed. Incubation with clomiphene citrate (1-1000 mumol/l; 1-4 h) induced a dose- and time-dependent increase in the percentage of acrosome-reacted spermatozoa (up to 100%). Acrosome reaction was associated with an impairment of both motility and viability. The maximal value for percentage of live reacted spermatozoa (37 +/- 1%) was obtained when cells were incubated for 1 h with 100 mumol/l of clomiphene citrate. Oestradiol neither affected sperm function when used alone nor inhibited clomiphene action. These results show that clomiphene strongly triggers the acrosome reaction, but that this action is not related to its anti-oestrogenic properties. PMID- 8345087 TI - Uterine flushing: a method to recover spermatozoa and leukocytes. AB - The process of sperm transport from the cervix, where a leukocytic reaction is initiated, through the uterus to gain access to the site of fertilization is very poorly understood. This preliminary study was designed to utilize a uterine flushing technique to determine firstly, the number of spermatozoa that can be recovered from the uterine cavity at 4 h post-insemination, around the time of ovulation, and secondly, to establish whether the spermatozoa initiate a leukocytic response while present. Uterine flushing was carried out in 10 potentially fertile women at 4 h post-insemination with donor semen, 24-36 h after the onset of the luteinizing hormone (LH) surge. The flush fluid was analysed for the numbers of spermatozoa and leukocytes present. In 8/10 women spermatozoa were retrieved from the uterus, in consistently low numbers (median 46, range 3-415). In 5/5 women leukocytes were recovered (median, 2.75 x 10(8)/l, range 2.0 x 10(8)-12.7 x 10(8)/l) from an origin other than peripheral blood contamination. These results suggest firstly that the flushing technique was a consistent method for retrieving spermatozoa and leukocytes from the uterine cavity, secondly that only low numbers of spermatozoa can be retrieved on flushing and thirdly that the leukocytic reaction to spermatozoa extends to the uterine cavity. PMID- 8345089 TI - Opening of the mouse zona pellucida by laser without a micromanipulator. AB - A contact-free laser system is described for ablation of the embryonic mouse zona pellucida using a pulsed excimer 308 nm laser. Effects on further embryonic development were evaluated. Zonae of 8- to 16-cell mouse embryos were either lased (n = 189), zona-drilled with acidified Tyrode's solution (n = 183) or left zona-intact (n = 188). Blastocyst formation (99-100%) was similar in the three groups. Hatching occurred earlier in lased embryos compared to those of the control group. These blastocysts hatched through the laser ablated area. Significantly more embryos were hatching on day 4 in the conventionally drilled group when compared to the laser treated group (50% versus 24% respectively). On day 7 of development, significantly (P < 0.05) more embryos conventionally zona drilled (37%) were intact than those which were previously laser treated (10%). Abnormal development was also noted in a small group of embryos which were lased just on the outside of the zona in comparison to 1/3 of an embryonic width away from the zona. The current results suggest that apparently precise zona laser ablation with an excimer laser at 308 nm may have potential adverse effects which may only be manifested after a prolonged period of culture past the cavitation stage. However, implantation rates of morphologically normal laser abalated embryos were not impaired when compared to control embryos. PMID- 8345088 TI - Ovarian function, tubal viability and pregnancy after tubo-ovarian transplantation in the rabbit. AB - A rabbit model was developed for microsurgical en-bloc vascularized tubo-ovarian allograft. Transplantation of tube and ovary from donors to tubo-oophorectomized recipients was technically successful in 50 rabbits. After surgery, animals were randomly allocated into two groups: animals in group A received cyclosporine for immunosuppression; animals in group B did not receive immunosuppressive therapy. In group A, 16 animals survived the transplant procedure and six animals became pregnant (38%). No pregnancies were obtained among animals in group B. In group A, plasma concentrations of ovarian and pituitary hormones were similar to those found in non-transplanted animals. Our results show firstly that tubo-ovarian transplantation is technically feasible, and secondly that cyclosporine improves not only tubal viability but also ovarian function after transplantation. PMID- 8345090 TI - The effects of the sperm motility activators 2-deoxyadenosine and pentoxifylline used for sperm micro-injection on mouse and human embryo development. AB - The sperm motility stimulants 2-deoxyadenosine (DOA) and pentoxifylline (PTF), used to improve the success of insemination and sperm micro-injection for low motility sperm samples, were studied for their effects on the developmental capacity of mouse and human oocytes. When human oocytes were micro-injected with spermatozoa in 3 mM DOA 80% of them became blocked at the 1-cell pronuclear stage. However, when spermatozoa in 3 mM PTF were used for micro-injection or when spermatozoa were washed to remove DOA before micro-injection only a few oocytes (9-10%) were blocked. Pregnancies occurred in five of 14 patients into whom cleaving embryos from all three treatments had been transferred, indicating that once cleavage was initiated, development of embryos occurred at expected rates. Exposure of mouse oocytes to DOA for a short period during insemination (4 6 h) or a longer period during the pronuclear cell cycle (18-20 h) significantly reduced cleavage beyond the 2-cell stage, resulting in a dramatic reduction in blastocyst formation. PTF did not significantly reduce mouse embryo development. Similar results were obtained for oocytes inseminated in vitro or micro-injected with a spermatozoon into the perivitelline space. Neither DOA nor PTF increased fertilization of mouse oocytes. PTF reduced fertilization, particularly in cumulus-enclosed oocytes and oocytes micro-injected with spermatozoa in PTF. We conclude that DOA is a potent inhibitor of embryo development and oocytes should not be exposed to DOA. Exposure of oocytes to PTF had little effect on their subsequent development but treatment of cauda epididymal mouse spermatozoa can reduce their fertilizing capacity. PMID- 8345091 TI - Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin. AB - To assess the risk of miscarriage after in-vitro fertilization (IVF) with respect to age, cause of infertility, ovarian morphology and treatment regimen, a retrospective analysis was performed of the first 1060 pregnancies conceived between June 1984 and July 1990 as a result of 7623 IVF cycles. Superovulation induction was achieved with human menopausal gonadotrophin (HMG) and/or purified follicle stimulating hormone (FSH) together with either clomiphene citrate or the gonadotrophin hormone-releasing hormone (GnRH) agonist buserelin, the latter either as a short 'flare' regimen or as a 'long' regimen to induce pituitary desensitization. There were 282 spontaneous abortions (26.6%) and 54 ectopic pregnancies (5.1%). The mean age of women with ongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2 (SD 4.1) years in those who miscarried, which were significantly different (P = 0.008). There was no relation between the miscarriage rate and the indication for IVF. The miscarriage rate was 23.6% in women with normal ovaries compared with 35.8% in those with polycystic ovaries [P = 0.0038, 95% confidence interval (CI) 4.68-23.10%]. There was no difference in the miscarriage rate between treatment with HMG or FSH. Women whose ovaries were normal on ultrasound were just as likely to miscarry if they were treated with clomiphene or with the long buserelin protocol. Those with polycystic ovaries, however, had a significant reduction in the rate of miscarriage when treated with the long buserelin protocol, 20.3% (15/74), compared with clomiphene citrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82-40.09%). PMID- 8345092 TI - Evidence for decidua-trophoblast interactions in early human pregnancy. AB - Medium conditioned by decidual cells decreased the growth of cultured BeWo choriocarcinoma cells. The degree of inhibition was dependent on the concentration of the conditioned medium used, and suggested that maternal decidua might regulate the growth of the fetal placenta. Medium from BeWo cells and primary trophoblast had the opposing effect and increased the growth of cultured decidual cells for up to 120 h of culture. These results suggest that a regulatory loop to control placental and decidual growth exists at the materno fetal interface, and this may be an important factor in the development of adequate placentation and the subsequent growth of the placenta during pregnancy. PMID- 8345093 TI - Family planning: cultural and religious perspectives. AB - The world population explosion has caused political leaders to look upon national and regional birth control projects as vital. Support for regulation of individual fertility has been evident in all cultures, and at all times, even in those societies in which social and religious rules have favoured the abundant production of children. As the secularization of Western society and scientific enquiry gained momentum during the modern period, knowledge of reproduction increased and was applied to control human population growth. The various methods of contraception and their development through the years from the ancient ideas to the modern era are presented. Each approach to fertility control has its advantages and disadvantages. No one method is perfect for everyone, for every clinical setting, and in every culture. Higher levels of fertility have been associated with 'traditional', religious prohibitions on some forms of birth control, 'traditional' values about the importance of children and the priority of family, and 'traditional' family and gender roles reinforced by religion. The attitude of the main religious groups to contraceptive practice is discussed. PMID- 8345094 TI - Recommendations of the ESHRE workshop on 'Unexplained Infertility'. Anacapri, August 28-9, 1992. PMID- 8345095 TI - Clomiphene citrate and pregnancy loss. PMID- 8345097 TI - Mutagenic sensitivity of human post-spermatogonial cells. PMID- 8345096 TI - Population growth. PMID- 8345098 TI - Treatment of Wernicke's aphasia with jargon: a case study. AB - This case study concerns an adult with Wernicke's aphasia characterized by neologistic jargon and a severe auditory comprehension deficit. No communicative or linguistic improvements had been observed after eight months poststroke. Up until this time, therapeutic intervention was aimed at managing the patient's rambling communicative style and improving auditory comprehension skills. A therapeutic regimen was introduced that focused on visual/written information and included a hierarchy of visual word and sentence comprehension tasks. All auditory/verbal stimulus presentation was eliminated. After two months on the program, improvement was noted in naming abilities and general ability to communicate in conversation, including a reduction of neologistic jargon and an increase in semantic jargon. No improvement was noted in auditory comprehension. The visual program may have facilitated the patient's general attentional set, thereby possibly contributing to her improvement in communicative style and sensitivity to conversational interactions with others. PMID- 8345099 TI - Word retrieval in fluent and nonfluent dysphasia: utilization of pictogram. AB - Connected speech samples were elicited from 10 nonfluent and 10 fluent dysphasic subjects utilizing two contexts, picture and pictogram descriptions. Incidences of word retrieval problems were identified and assigned to nine word retrieval categories. Results revealed pictogram elicited a greater incidence of word retrieval problems, and therefore, proved as a more informative context for identifying word retrieval problems in mild dysphasia. Also, certain word retrieval categories were selectively used by specific dysphasic classification categories and severity levels. PMID- 8345101 TI - Istvan Tork 1939-1992. PMID- 8345100 TI - Common hemisphericity of language and music in a musician. A case report. AB - Aphasia coupled with amusia is reported in a 73-year-old male musician who was a lawyer by profession. This condition followed an ischemic stroke in the lateral aspect of the parieto-occipital region of the left hemisphere. The patient's music production exhibits jargon amusia, similar to that in his verbal production. This case supports the thesis that language and music may share a common hemisphere. PMID- 8345102 TI - Retinal degeneration in the nervous mutant mouse. II. Electron microscopic analysis. AB - Nervous mutant mice (nr/nr) show a rapid loss of most of cerebellar Purkinje cells between the ages of 3 and 7 weeks, as well as a progressive photoreceptor cell degeneration that occurs most rapidly between postnatal days (P) 13 and 19, but with a much slower attrition during the subsequent months. We have carried out an electron microscopic analysis of nr/nr and littermate control mice at representative ages to characterize the subcellular cytopathological changes in this form of retinal degeneration, to gain insight into photoreceptor cell degeneration mechanisms by comparing these changes to those in other rodent forms of retinal degeneration, and to compare the photoreceptor changes with those of cerebellar Purkinje cells. Ultrastructural observations were limited to rod photoreceptors, since the number of cones was limited in our micrographs. The retinas of nr/nr mutant mice can be distinguished from those of normal littermates as early as postnatal day (P) 6. At this time, some of the mitochondria in rod inner segments are larger and more rounded than normal. This represents the earliest cytopathological change thus far observed in this mutant. As early as P9 and thereafter, the volume and integrity of rod outer segment membranes are reduced from normal. In the inner segments of some rod photoreceptor cells, there is a reduction in the volume or number of polyribosomes as early as P11, a reduction in rough endoplasmic reticulum as early as P13, and reduced incidence and less organized Golgi membranes as early as P16. Qualitative evaluation and quantitative stereological analysis show that the enlarged mitochondria in rod inner segments never become normal in shape or size. No changes are seen in the inner retinal layers at any age. Despite similarities with inherited retinal dystrophy in the Royal College of Surgeons rat, as noted in the original description of retinal degeneration in nr/nr mice, ultrastructural features clearly distinguish these mutants. Moreover, nr/nr mice can be distinguished from all other murine forms of retinal degeneration by electron microscopy. PMID- 8345104 TI - Developmental study of GnRH neuronal projections to the medial basal hypothalamus of the male Djungarian hamster. AB - The present study in the male Djungarian hamster determined the neuroanatomical distribution and morphology of gonadotropin-releasing hormone (GnRH) neurons which innervate the medial basal hypothalamus during sexual maturation. Prepubertal, peripubertal, and postpubertal males were perfused, brains were removed, and crystals of the fluorescent tract tracer, DiI, were implanted directly into the median eminence of the brain. Eight weeks later, brains were sectioned and processed for GnRH immunofluorescence. At all ages, GnRH cell bodies were bipolar or unipolar; both subtypes were labeled with DiI in proportion to their respective numbers in each brain region. GnRH perikarya were distributed in a diffuse ventromedial continuum from the septum through the anterior hypothalamus. In prepubertal males, DiI was present in the majority of GnRH neurons (54% of total) that were located in brain regions rostral to and including the medial preoptic area. In lateral and caudal brain areas, fewer GnRH perikarya contained DiI (28% of total or less). With sexual maturation, fewer GnRH somata were labeled with DiI in areas rostral to the hypothalamus. The data suggest that bipolar and unipolar GnRH neurons in the forebrain, rostral to the preoptic area, are major contributors to the GnRH innervation of the median eminence in the male Djungarian hamster. With the onset of puberty, the finding that decreasing numbers of GnRH perikarya directly project to the medial basal hypothalamus suggests that fewer GnRH neurons constitute the final common pathway that controls gonadotropin secretion. PMID- 8345103 TI - Differential time course and spatial expression of Fos, Jun, and Krox-24 proteins in spinal cord of rats undergoing subacute or chronic somatic inflammation. AB - We have used the evoked expression of both immediate early gene (IEG)-encoded proteins (Krox-24, c-Fos, Fos B, Jun D, Jun B, c-Jun), and dynorphin to monitor sensory processing in the spinal cords of rats undergoing subacute or chronic somatic inflammation (i.e., subcutaneous inflammation of the plantar foot and monoarthritis, respectively). Behavioral and immunocytochemical approaches were conducted in parallel up to 15 weeks postinjection in order to detect possible relationships between clinical evolution and spatiotemporal pattern of IEG encoded protein expression. Each disease had specific characteristics both in terms of their clinical evolution and pattern of evoked protein expression. All IEG proteins were expressed in both cases. Most of the staining was observed in both the superficial layers of the dorsal horn and deep dorsal horn (laminae V VII and X). Monoarthritis was distinguished by a high level of total protein expression. Staining was especially dense in the deep dorsal horn. More labelled cells were observed at 1-2 days and at 2 weeks postinjection, corresponding to the initiation and progressive phases of the disease, respectively. Subcutaneous inflammation was characterized by a moderate level of total IEG expression. More labelled cells were observed in the first day following injection. It is the relative degree of expression of each IEG-encoded protein with regard to the others that characterized the progression of the diseases. Early stages of the diseases coincided with the expression of all Fos and Jun proteins, while late stages showed an increase in Jun D and Fos B involvement; Krox-24 was induced mostly during the early phases and/or periods of paroxysm of the diseases. Persistent stimulation was characterized by a predominant expression in deep versus superficial layers of the dorsal horn. Evoked expression of c-Jun in motoneurons was only observed in monoarthritis. The peak of dynorphin expression was late in regard to both the induction of inflammation and period of maximal IEG-encoded protein expression. The present work indicates that the neural processing that takes place during progression of these diseases can be monitored well at the spinal cord level by using the expression of an array of IEG-encoded proteins. Study of long term evolutive diseases and especially those that evolve into chronicity can largely benefit from such an approach. PMID- 8345105 TI - Collateral sprouting in the electrosensory lateral line lobe of weakly electric teleosts (gymnotiformes) following ricin ablation. AB - Sprouted collateral axons were observed in the electrosensory lateral line lobe (ELL) of gymnotiform teleosts (Apteronotus leptorhynchus) following the ablation of the supraorbital branch of the anterior lateral line nerve. Ablation was accomplished by using microinjections of the toxic lectin ricin. Sprouted axons were followed for up to 26 weeks postablation. Ricin exposure severely reduced axonal numbers and the peripheral electroreceptors in the region innervated by these fibers. To visualize sprouted fibers, intact lateral line afferent nerve branches were anterogradely labelled with the neuronal tract tracers horseradish peroxidase or cobalt chloride, or the monoclonal antibody Q26A3. Within the four somatotopically organized ELL segments, sprouted collaterals were first observed two weeks after ricin injection in the medial and centromedial segments, and four weeks postinjection in the centrolateral and lateral segments. Sprouting involved intrasegmental, horizontally directed axons from adjacent nerve branch terminal fields, and mixed intra- and extrasegmental, dorsally directed axons from the ELL deep fiber layer. The sprouting response was robust but variable in its timing, peaking between 6 and 12 weeks. Subsequently, the intrasegmental, horizontally directed fibers were retained but the mixed dorsally directed fibers, including all extrasegmental axons, were retracted. Therefore, this sprouting response appears to consist of a collateral overproduction followed by a selective axonal retraction. In our view, the most likely explanation for this axonal retraction is that the descending inputs from the isthmus and the cerebellum, as well as commissural fibers from the contralateral ELL, maintain established somatotopic relationships by eliminating somatotopically mismatched sprouted collaterals. PMID- 8345106 TI - Spatial organization of inner hair cell synapses and cochlear spiral ganglion neurons. AB - The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus was previously investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions resulted in highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN caused degeneration of cells within the scala tympani part of the ganglion, whereas medial ablations within the AVCN induced degeneration of the scala vestibuli aspect of the ganglion. The peripheral axons also degenerated and this fiber loss exhibited selective topographies that paralleled the cell loss within the spiral ganglion, although this phenomenon was more prominent in the proximal part of the osseous spiral lamina near the ganglion and less obvious more distally near the habenula perforata. In this investigation, inner hair cells (IHCs) from these selective lesion cases were evaluated by electron microscopy of serial sections through the basal synaptic regions. Results demonstrated differential degeneration of afferent synapses, with greater (but not completely selective) loss of pillar synapses after lateral AVCN lesions and greater loss of modiolar synapses after medial lesions. Because auditory nerve fibers of different spontaneous discharge rates (SRs) have different spatial distributions on the IHC (Liberman, Science 216:1239, 1982), our results suggest that this SR-based organization is maintained in a topographic organization across the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion cell cluster and carried into the ventral cochlear nuclei (VCN). Thus, in addition to the spiral frequency organization represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly organization of inputs from high- and low-SR fibers across the lateral-to-medial dimension of the VCN such that the lateral isofrequency laminae receive a proportionately greater input from high-SR fibers, whereas medial isofrequency laminae receive preferential input from low- and medium-SR fibers. PMID- 8345107 TI - JUN, FOS, KROX, and CREB transcription factor proteins in the rat cortex: basal expression and induction by spreading depression and epileptic seizures. AB - The expression of the nuclear c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB transcription factors was investigated in the cortex of adult rats by immunocytochemistry. The expression patterns were studied in untreated rats and up to 24 hours following topical application of 1 M KCl to the cortical surface (KCl) or i.v. injection of bicuculline (BIC). Topical KCl induced cortical spreading depression and systemic injection of bicuculline evoked generalized tonic-clonic seizures. In untreated rats, JUN B, c-FOS, and FOS B were expressed in a small number of neurons in the piriform, perirhinal, entorhinal, and insular cortex and in layers II, III, and VI of all neocortical areas. In contrast, c JUN, JUN D, and KROX-24 were expressed in all cortical layers but with different intensities of immunoreactivity (IR): c-JUN-IR was generally weak and predominantly present in layers II, III, and VI. JUN D-IR was equally strong in all layers. KROX-24 showed a prominent expression in layers II, IV, and VI. The CREB protein exhibited a slight preponderance in layer II and piriform cortex. Following KCl or BIC, a strong induction was seen for c-FOS, JUN B, and KROX-24, whereas c-JUN, JUN D, and FOS B showed only a moderate increase compared to basal levels. Changes of CREB-IR could not be detected. The localization of induced JUN, FOS, and KROX proteins reflected the pattern of labelling in untreated animals but demonstrated a higher intensity of labelling and an increased number of immunoreactive nuclei. The intensity and persistence of IR as well as the number of labelled cells following BIC exceeded those following KCl. Following BIC, increased levels of FOS B and JUN D were still present after 24 hours. Counterstaining with cresyl-violet and GFAP, a marker for astrocytes, revealed that JUN, FOS, and KROX proteins were expressed in neurons but not in glial cell populations. The present data demonstrate that CREB, JUN, FOS, and KROX transcription factors exhibit a layer-specific expression in the cerebral cortex with only slight area-specific differences both in untreated rats and following stimulation with KCl and BIC. The expression of transcription factor proteins indicate complex molecular genetic changes in cortical neurons due to pathophysiological events such as seizure activity and spreading depression. PMID- 8345108 TI - Development of the olfactory organ in the zebrafish, Brachydanio rerio. AB - The development of the olfactory organ of the zebrafish, from the forming of early placode to the adult organ, was investigated by electron microscopy and DiI labeling. The olfactory placode is formed by a subepidermal layer of cells. These cells differ from those of the epidermis as well as from brain cells, and they do not mingle either with epidermal or with brain cells. No migration of cells from the brain or the epidermis towards the subepidermal cell layer has been observed. The cells of the subepidermal layer seem to form all cell types of the olfactory mucosa, i.e., basal cells, ciliated and microvillous receptor cells, supporting cells, and ciliated nonsensory cells. Axons grow into the forebrain at a very early stage when the epidermis still covers the placode completely. Dendrites grow out when the epidermis separates, building the olfactory pit. This process implicates neither cell lysis nor cell degeneration. The olfactory pit forms a rosette with a midline raphe and olfactory lamellae. The incurrent nostril is separated from the excurrent nostril by a funnel-shaped structure. Differentiation of the olfactory placode in the embryo is accomplished very quickly, whereas the development into the adult organ during larval stages is a slow process. PMID- 8345109 TI - The differentiation between neuroglia and connective tissue sheath in insect ganglia revisited: the neural lamella and perineurial sheath cells are absent in a mesodermless mutant of Drosophila. AB - Two morphogenetic mutations, twist and Delta, that affect the embryonic development of Drosophila in known ways were used to examine the derivation and function of the outer layers of the central nervous system (CNS). Both the extracellular neural lamella, which ensheaths the CNS, and its source, the underlying perineurial sheath cell layer, fail to develop in Drosophila embryos that are homozygous for a loss of function mutation in the twist gene, and which thus lack mesodermal derivatives. The cell layer immediately below the perineurial sheath cells, here termed barrier glial cells, constitute the ion permeability barrier in wild-type embryos. They are present in twist mutant embryos, appear to be normal at the ultrastructural level, and function as a blood-brain ion barrier. The apparent derivation of perineurial sheath cells from mesodermal precursors distinguishes them from neurons, glia and other nonneural components of the CNS, such as tracheae, all of which are of ectodermal origin. We confirm Scharrer's interpretation of the relationship between the perineurium and underlying neuroglia. In embryos homozygous for the neurogenic mutant Delta, an embryonic lethal in which excess ventral blastoderm gives rise to neuroblasts, the CNS forms as an amorphous cell mass, with discontinuous perineurial sheath and barrier glial cell layers. We propose that the cell mass is permeable to lanthanum ions and fails to form a blood-brain barrier because volume growth prevents the formation of continuous surface cell layers. PMID- 8345110 TI - Continuing education and health care reform. PMID- 8345111 TI - Preparing for mandatory continuing education--assessing interests. AB - Assessment of needs is the foundation of nursing practice as well as nursing education. To increase responsivity to the continuing education (CE) needs of registered nurses (RNs) within a small, yet diverse, mid-Atlantic state in which CE was recently mandated for relicensure, a telephone survey was used to gather information on a large nonrandomized sample of RNs. Preferences for types of programming, methods and locations for acquiring CE, scheduling, academic credit in addition to CE credit, and an automated service for maintaining CE attendance records were identified. This study presents an overview of survey results helpful in planning offerings most likely to attract and satisfy nurses. PMID- 8345112 TI - Collaborative preceptor training: a creative approach in tough times. AB - Rapid changes in the health care environment have challenged educators to find more efficient methods of developing nurses. These demands are leading to the use of collaborative approaches to education. Nurse educators have also found that they have to rely on preceptors for orientation of new employees. The Texas Medical Center Collaborative Preceptor Program was developed in 1989 to prepare nursing preceptors for all nine participating institutions. The goals of the program were to increase efficient use of instructor time, standardize preceptor preparation in the Texas Medical Center, and offer more programs and prepare more nurses per year than each individual institution could do alone. There were many unexpected benefits as well, and future plans for collaboration are already being formulated. PMID- 8345113 TI - Predictors of clinical performance of new graduate nurses participating in preceptor orientation programs. AB - Orientation programs providing designated preceptors for graduate nurses are used widely, but few studies support their success in assisting graduates to assume staff nurse positions. This study addressed the research question: What variables are related to clinical performance among new nursing graduates? Self-evaluations of clinical performance, preceptor evaluations, and demographic information were collected from a sample of 65 new graduates. The most useful predictors of clinical performance scores were support provided by other nurse friends, preceptor skills, and emotional support provided by preceptors. Participation in formal support groups, however, was not found to be a predictor. PMID- 8345114 TI - Clinical ladder development: implementing contract learning. AB - Expanding the clinical ladder concept in nursing at the Presbyterian Hospital in New York prompted the Department of Education, Research, and Development to further implement contract learning as an innovative adult education technique. The process was applied in orienting new Clinical Nurse IIs (experienced nurse preceptors) and Clinical Nurse IIIs (assistants to the Nursing Care Clinicians) to their advanced clinical roles. The process of implementation, the development of learning contracts, and the week-long workshop designed for each of the new clinical leaders is discussed. PMID- 8345115 TI - Comparison of classroom instruction and independent study in body mechanics. AB - This study was designed to determine which method of instruction in body mechanics results in the higher subsequent use of the techniques taught. Two groups were formed from nursing personnel at a rural general medical-surgical hospital in the southwestern United States. Subjects from the direct care nursing staff were randomly assigned to one of the two groups. One group attended two hours of classroom instruction in body mechanics, while the other completed an independent study module. Subjects were pre- and posttested using the Work Related Body Mechanics Evaluation (Carlton, 1987) while performing a standardized lifting task in the clinical setting. Using analysis of covariance, no significant differences were found in the posttest scores of the two groups. PMID- 8345116 TI - Revisiting CPR knowledge and skills among registered nurses. AB - The purpose of this investigation was to explore facets involved in the retention of the cognitive knowledge and psychomotor skills of cardiopulmonary resuscitation (CPR) by 73 RNs from three general hospitals. Data analysis indicated that cognitive knowledge was adequately retained but that skills were not. Product-moment correlation coefficients showed that the number of CPR courses taken, certification as a CPR instructor, the number of years certified, and time since last certification were significantly related to skill scores. Findings prompt questions of appropriateness of the usual certification procedures for hospital-based RNs. PMID- 8345117 TI - Codependency in nursing: using a simulation/gaming teaching method. AB - Practicing nurses can benefit by learning to differentiate their caretaking (potentially destructive) from their caregiving (constructive) behaviors, and by learning strategies to facilitate caregiving. A new simulation/game was developed to assist nurses to recognize codependent behaviors in themselves and others and to practice some alternative patterns of behavior. This team-based simulation/game, "The Climb," uses the metaphor of a mountain-climbing expedition. The experiences of the journey promote dynamic insights into the consequences of codependency in the professional and personal lives of the nurse. PMID- 8345118 TI - The mock isolation room: a fun way to review infection control. AB - The Infection Control Unit of the Montreal General Hospital implemented a Mock Isolation Room that tested nurses' knowledge with a review of common medical device and isolation infractions and recommendations. Consultants reinforced correct practices and clarified misconceptions. The Mock Isolation Room is recommended as an effective review strategy that encompasses the principles of adult learning. The material was identified by the nurses as clinically relevant and the learning method was considered to be fun and effective. The exercise can also be used as a needs assessment tool. PMID- 8345119 TI - Don't go 'way, it's time to play ... the safety game! AB - In an attempt to decrease the amount of time and dollars spent while increasing positive staff response, Emanual Hospital in Portland, Oregon, developed a game format to review required safety information. The game was piloted, then presented to the hospital's safety committee where it was approved as part of the hospital's education program. The game has significantly increased the percentage of staff participation in required classes. At the same time, cost of presenting the classes has decreased significantly. PMID- 8345120 TI - Summary of conclusions from a consensus panel of experts on health attributes of lactic cultures: significance to fluid milk products containing cultures. AB - A panel of experts sponsored by the California Dairy Research Foundation was convened on January 31, 1992 to discuss the effect of the consumption of lactic cultures on human health. The panel was composed of 10 scientists with diverse applicable specialties. Topics discussed included lactose digestion, diarrheal diseases, chronic kidney disease, cancer, adherence, immune system stimulation, cholesterol reduction, constipation, and safety. Legitimacy of health claims and research needs for these areas were determined. The panel noted the promising results in the areas of positive effects of ingestion of lactic cultures on lactose digestion, some diarrheal illnesses, small bowel overgrowth associated with chronic kidney disease, and reduction of fecal enzymes that may play a role in colon cancer. However, additional research is necessary to confirm the effects in all of these areas. A coordinated research effort between microbiologists and clinicians is essential for the most effective research to ensure the choice of best available strains, the best conditions of analysis, and the best clinical models. PMID- 8345121 TI - Shelf-life of pasteurized process cheese spreads made from cheddar cheese manufactured with a nisin-producing starter culture. AB - Cheddar cheese made with a nisin-producing starter culture and Cheddar cheese made with a commercially available starter culture were used to manufacture pasteurized process cheese spreads at low and high moisture percentages (53 and 60%, respectively). Composition did not differ between spreads of similar moisture content with and without nisin. The nisin contents of cheese spreads were 301 and 387 IU/g at the high and low moisture percentages, respectively. Nisin was not inactivated by the thermal process used during cheese spread manufacture. Shelf-life of pasteurized process cheese spreads was determined during storage at 22 and 37 degrees C. Low moisture cheese spreads with nisin had a longer shelf-life than corresponding cheese spreads without nisin when cheeses were incubated at either temperature. High moisture cheese spreads with nisin had a longer shelf-life than control spreads when cheeses were incubated at 22 degrees C. However, shelf-life did not differ between high moisture spread with nisin and cheese spreads without nisin when cheeses were incubated at 37 degrees C. PMID- 8345123 TI - Composition of molecular species of triacylglycerols in bovine milk fat. AB - Triacylglycerols from bovine milk fat were fractionated by reversed-phase liquid chromatography. The fatty acid and triacylglycerol compositions of each fraction were determined by capillary gas chromatography. These data were used to determine the accurate proportions of 223 individual molecular species of even numbered triacylglycerols, accounting for 80% of total triacylglycerols (all percentages are expressed as moles per 100 mol). The three major triacylglycerols were butyroylpalmitoylacylglycerols, namely butyroylpalmitoyloleoylglycerol (4.2%), butyroyldipalmitoylglycerol (3.2%), and butyroylmyristoylpalmitoylglycerol (3.1%). Twenty-two triacylglycerols (> 1%) contained at least two of the four major long-chain fatty acids (C14:0, C16:0, C18:0, and C18:1). Among them were eight butyroyldiacylglycerols, the proportions of which reached 19% in total but only 12% when calculated on the basis of a random distribution of the fatty acids in the triacylglycerol molecules. More generally, most of the triacylglycerols that are composed of a short-chain fatty acid (C4:0 or C6:0) and two fatty acids in the range of C12 to C18 are preferentially synthesized by the mammary gland; their proportions (36% in total) were higher than the corresponding random values (24% in total). Conversely, the total amounts of simple (.4%) and mixed (2.9%) saturated long-chain (C14:0 to C18:0) triacylglycerols were much lower than those expected from random calculation (1.9 and 6.1%, respectively). PMID- 8345124 TI - Iron-binding properties of bovine lactoferrin in iron-rich solution. AB - The iron-binding properties of bovine lactoferrin in iron-rich solution were investigated. Ferrous iron was not stable in solution and was easily changed to the insoluble ferric state, but solubility of ferrous iron was stabilized by the presence of lactoferrin. However, casein hydrolysate or BSA was not effective in stabilizing iron in solution. As indicated by use of cibacron blue affinity gel, iron bound to lactoferrin, and the charge of supersaturated lactoferrin was higher than that of normal iron-saturated lactoferrin according to native PAGE electrophoresis. The evidence suggests that lactoferrin can bind iron at sites other than its chelate-binding sites, thereby stabilizing iron in solution. PMID- 8345122 TI - Application of a diphasic dialysis technique to the extraction of aflatoxins in dairy products. AB - A new method is described for the extraction of aflatoxins from milk and milk products based on a diphasic dialysis technique, followed by detection and quantification of aflatoxins by TLC. Recovery was 65 to 99% for aflatoxins B1, G1, and M1, and the detection limit in milk and yogurt was .01 to .02 ppb for all aflatoxins studied. In cheese, the detection limit was .03 to .04 ppb for aflatoxins B1 and G1 and .1 ppb for aflatoxin M1. The main advantages of this technique are its simplicity; sensitivity; very economical use of reagents, thereby minimizing environmental pollution; efficiency, allowing the quick processing of a high number of samples; use by laboratories with little equipment; and a sensitivity comparable with that of much more sophisticated techniques. PMID- 8345125 TI - Role of protein and lactose interactions in the age gelation of ultra-high temperature processed concentrated skim milk. AB - Skim milk was pasteurized, diafiltered, and concentrated three times by UF. Lactose or sucrose was then added at 3 or 6%. The five samples containing < .05% lactose, 3 and 6% lactose, and 3 and 6% sucrose were UHT processed at 140 degrees C for 4 s using indirect heating, collected aseptically in presterilized containers, and stored at 4, 20, and 35 degrees C. All samples stored at 4 and 20 degrees C gelled after 21 wk of storage. Samples stored at 35 degrees C did not gel. Browning occurred only in samples containing lactose stored at 35 degrees C. Proteolysis in gelled samples was shown by SDS-PAGE. Bands were due to proteolysis, protein crosslinking, and a streaking pattern in ungelled samples. Electron micrographs of gelled samples showed that various casein particles were connected by hairlike protrusions, but the micelles in ungelled samples were not connected and had few protrusions. The Maillard reaction neither promoted nor deferred age gelation. Protein modifications prevented gelation in samples stored at 35 degrees C. Age gelation was probably a two-step process in which dissociated proteins from the casein micelles reformed on micelles as hairlike protrusions. This process was followed by aggregation of the protein particles. PMID- 8345126 TI - Characteristics of beta-lactoglobulin binding to the all-trans-retinal moiety covalently immobilized on Celite. AB - All-trans-retinal was covalently immobilized on Celite and investigated as a bioselective adsorption matrix for beta-lactoglobulin. Two types of Celite supports were compared, indicating the best performance with 100/120 mesh, type R648. The R648 matrix yielded a high concentration (9.2 mumol/ml) of the ligand when the derivative was produced, and the derivatized matrix exhibited the best retention of beta-lactoglobulin. Binding of beta-lactoglobulin to the immobilized trans-retinal matrix is biospecific, but the affinity is dependent on pH and ionic strength. alpha-Lactalbumin is not bound to this bioselective adsorbant, so its elution was not retarded or affected by pH or buffer concentration. Affinity for beta-lactoglobulin was optimal at pH 5.14; a dissociation constant of 2.7 microM was obtained in .1 M buffer solutions. At pH 7.0, the affinity decreased 44-fold, and, below pH 3.5, no binding occurred. The estimated loading capacity based on chromatographic data was approximately 14 g/L (.75 mumol/ml) of support. PMID- 8345127 TI - Improving survival of culture bacteria in frozen desserts by microentrapment. AB - Lactobacillus bulgaricus cells were entrapped in beads of calcium alginate and evaluated for their ability to survive freezing processes. Cells survived freezing (without agitation) in ice milk mix much better than in distilled water, and more entrapped cells survived than did cells that were not entrapped. Glycerol and mannitol were cryoprotective, but glucose was not, when each was added (6%) separately to the beads. Entrapment protected the lactobacilli in batch frozen and continuously frozen ice milk mixes. The percentage of survival for entrapped and unentrapped cells in continuously frozen ice milk approximated 90 and 40%, respectively. Lactobacilli survived better in beads with mean diameters > 30 microns than in those averaging 15 microns. Addition of entrapped lactobacilli had no measurable effect on the sensory characteristics of the ice milk. PMID- 8345128 TI - Fertility of bull spermatozoa frozen in whole milk extender with trehalose, taurine, or blood serum. AB - Fertility of bull semen processed in heated whole milk-glycerol control semen extender with various additives was compared in six field trials. The additive in field trials 1 and 2 was 25.6 g of trehalose/L of the glycerol fraction of whole milk. Whole milk was heated to 95 degrees C for 10 min, cooled, and filtered 1 d before use (trial 1) or 3 d before use (trial 2). In field trial 3, 3.0 g/L of taurine were added to the glycerol fraction of whole milk. In field trial 4, specially prepared bovine serum (15% vol/vol) was included in the glycerol fraction of whole milk. Field trials 5 and 6 were larger fertility studies with trehalose in extenders prepared the day before use (trial 5) and 1 and 3 d before use (trial 6). Control and treated semen were coded and distributed randomly over a large group of professional inseminators. The 59-d nonreturn rates for control and treated semen, respectively, were as follows: trial 1, 74.1 and 73.7%; trial 2, 71.3 and 73.1%; trial 3, 74.9 and 70.9%; and trial 4, 75.1 and 71.6%. No significant differences resulted in trials 1 to 3, but bovine serum decreased the non-return rate in trial 4. Trials 5 and 6 resulted in nonsignificant improvement in fertility with added trehalose. Thus, these additives, useful as cryopreservatives or membrane protectors in other systems, did not enhance the fertility of sperm frozen in whole milk. PMID- 8345129 TI - Milk as a source of deoxyribonucleic acid and as a substrate for the polymerase chain reaction. AB - Somatic cells in milk were used as a source of DNA and as a substrate for the polymerase chain reaction. Successful DNA extraction required a minimum total of 17 x 10(6) cells in the milk sample. The DNA yield per cell was highly variable but comparable, on average, with the yield from peripheral blood leukocytes. In all cases, direct polymerase chain reaction on milk samples, using a variety of primer pairs, yielded amplified products of correct size that were identical to those obtained by polymerase chain reaction of purified DNA extracted from milk or blood. Milk and DNA extracted from milk served as substrates for direct sequencing of part of the bovine growth hormone gene. Milk samples with added preservative were stored over 200 d without effect on the polymerase chain reaction. Thus, milk can often substitute for blood as a source of DNA for Southern blot analysis and is a preferred substrate for the polymerase chain reaction. The technical convenience of milk as a source of DNA can be expected to increase the field of application of marker-based methods for genetic analysis and genetic improvement of economic traits in dairy cattle. PMID- 8345130 TI - Evaluation of 57 teat sanitizers using excised cow teats. AB - Fifty-seven teat dip formulations were tested for germicidal activity with an excised teat assay. Streptococcus agalactiae (ATCC 27956), Staphylococcus aureus (ATCC 29740), and Escherichia coli+ (a wild strain isolated from an Ohio cow 2956RR during the dry period) were used. Log reductions ranged from 5.6480 to 1.8330 for Strep. agalactiae compared with undipped controls. Staphylococcus aureus were reduced from 4.8972 to 1.0102. Escherichia coli were reduced from 5.8677 to 1.1450. The percentages of the products tested that had log reductions < 3 against Strep. agalactiae, Staph. aureus, and E. coli were 24, 30, and 61. Four teat dip formulations contained 4% sodium hypochlorite; all were effective against Strep. agalactiae, Staph. aureus, and E. coli. The three formulations containing glutaraldehyde were effective against the three mastitis pathogens. Formulations containing 1 and .5% iodine were not consistently effective against Strep. agalactiae, Staph. aureus, or E. coli. Teat sanitizers containing .5% chlorhexidine also showed inconsistency. Variations in formulation for products containing iodine or chlorhexidine affected germicidal activity. PMID- 8345131 TI - Regulation of growth and development of the gastrointestinal tract. PMID- 8345132 TI - Role of peptide YY in the endocrine control of digestion. AB - Peptide YY is released into the circulation after ingestion of a meal, a response that is markedly enhanced in patients with malabsorption. The enhanced release of peptide YY slows gastric emptying and transit of meals through the small intestine. The net effect is increased efficiency of digestion and absorption of nutrients. Once the efficiency of nutrient utilization is optimized and the delivery of unabsorbed nutrients to the distal gut decreased, peptide YY release is inhibited. As peptide YY slows colonic transit, it could also improve salvage of unabsorbed nutrients by enhancing bacterial production of volatile fatty acids and their subsequent absorption by the colonic mucosa. PMID- 8345133 TI - Nutritional regulation of postruminal digestive enzymes in ruminants. AB - Nutritional regulation of digestive enzymes has received limited study in ruminants. Comparable studies with nonruminants report adaptations occurring in pancreatic and mucosal enzyme concentrations and synthesis in response to increased consumption of carbohydrate, lipid, or protein. Adaptations in carbohydrases apparently are mediated through changes in blood glucose and insulin, and changes in lipase are mediated through changes in circulating beta hydroxybutyrate. Increased synthesis and secretion of pancreatic proteases apparently are mediated directly through luminal effects of protein, possibly through a messenger peptide. Available information for ruminants suggests that pancreatic alpha-amylase concentration increases with increased energy intake, but not with increased carbohydrate intake, independent of energy. This result may indicate an adaptation mechanism similar to that of nonruminants, one that is mediated through increased glucose turnover, not intestinal carbohydrate supply alone. Increased intake of energy or increased intestinal supply of carbohydrates results in little or no increase in mucosal carbohydrases in the ruminant. Comparable data for effects of changing intestinal supply of protein are limited to the developing ruminant. Experiments involving lipid feeding are not available, but duodenal lipid infusion decreases pancreatic lipase secretion. Ruminant data are inadequate to predict accurately an adaptive response to feeding any diet. PMID- 8345134 TI - Manipulation of gastrointestinal nutrient delivery in livestock. AB - Discussed herein are the constraints of nutrient delivery from the gastrointestinal tract that are placed on postabsorptive synthetic processes in highly selected strains of domestic livestock or livestock treated with growth promotants exogenously or via transgenic manipulation. Emphasis is placed on the discussion of recent advances in the knowledge of the regulation and manipulation of digestion and the absorption by the intestinal epithelium. Slaframine, a muscarinic exocrine secretagogue with a high affinity for the gastrointestinal tract, and epidermal growth factor may have practical potential for the manipulation of digestion and absorption, respectively. Special consideration is given to energetic considerations that must accompany any manipulation of gastrointestinal function. Down-regulation and up-regulation of mechanisms must be equally considered as this area is explored further. PMID- 8345135 TI - Nutrient metabolism by gut tissues. AB - The gut uses a disproportionate amount of energy (about 25% of total oxygen consumption) for the size of the tissue (about 6% of body weight). Therefore, knowledge of metabolites used in gut tissues is important to assess nutrient needs. The VFA produced intraruminally are used to varying degrees by rumen epithelial tissue. A review of net portal absorption data essentially confirms earlier studies that show acetate, propionate, and butyrate metabolism by stomach tissue to be 30, 50, and 90%, respectively, of ruminant production. Glucose also is used by rumen epithelial tissue; however, glutamine appears to be a poor substrate for energy production. Tissue of the small intestine uses glutamine, glucose, and ketones but does not use VFA very well for energy. Cecal and colonic tissues can use glucose and glutamine for energy, but butyrate is the preferred substrate in both tissues. PMID- 8345136 TI - American Association of Dental Schools 1992-93 annual proceedings. March 8, 1992 March 10, 1993. Including the proceedings of the 1993 annual session. PMID- 8345137 TI - Independently living seniors and vitamin therapy. What nurses should know. AB - 1. Over-the-counter vitamin/mineral supplement consumption has become customary among many older adults in the United States. Inappropriately used, these dietary supplements possess the capacity for producing toxic reactions. 2. Vitamins/minerals can be harmful when taken incorrectly or in lavish proportions. Even though the Food and Drug Administration does not classify dietary supplements as drugs, a vitamin must be viewed as a medication when consumed in excess. Excessive intakes of vitamins A, C, and D are known to have adverse effects. 3. It is imperative that nurses incorporate vitamin therapy assessment into their practice, whether it be administration, education, or research. Unless ordered by a physician for a medically based pathology, nutrient supplementation should not exceed the RDA levels for older adults, if supplementation is used at all. PMID- 8345138 TI - Nursing implications. Functional status of older persons with schizophrenia. AB - 1. Older persons with schizophrenia underreport medical symptoms and overrate physical well-being. 2. Changes in mental functioning and ability to perform activities of daily living are often the first signs of physical illness. 3. Completing a drug inventory for tardive dyskinesia and extrapyramidal side effects should be ongoing. 4. Social assessment and intervention should focus on the well part of the person. PMID- 8345139 TI - Clinical manifestations. Failure to thrive in the elderly. AB - 1. Failure to thrive (FTT) is a diagnosis used with increasing frequency in the acute care setting. The purpose of this study was to determine how the diagnosis of FTT was being applied to the geriatric population. 2. FTT was used in the study population to describe the general deterioration seen in patients with chronic or incurable illnesses. Many patients were near the terminal stage. The diagnosis was not used specifically for the geriatric population; there was a lack of specificity in the diagnosis and treatment of FTT. 3. Common complaints of patients diagnosed as FTT included ADL changes, weight loss, and anorexia. Nursing care can significantly contribute to the management of symptoms and the prevention of complications. PMID- 8345140 TI - The case for an integrated health care reform plan. PMID- 8345141 TI - Geriatric nursing. Health care reform in Scotland. AB - 1. The United Kingdom's private practitioners are awarded a yearly budget by the National Health Service. Within that budget, the practitioners design a practice that fits into this financial constraint. Certain practice guidelines are also dictated by the government. A reform measure, "Working With People," has been introduced to correct flaws in the system. 2. "Working With People" has created a considerable amount of rhetoric and debate. The paper has been enthusiastically supported by independent sector interests and encourages privatization and development of self-governing hospitals. 3. Gerontological nursing education and practice in the United States has much to gain from its colleagues in the UK--and vice versa. There is room for collaboration and consultation from nursing professionals in the United States to avoid the many negatives that have faced the industry there. PMID- 8345142 TI - Focus on breast cancer screening. PMID- 8345143 TI - Elder hearing aids. Infrared listening device in a geriatric day center. AB - 1. An infrared listening device (IRLD) is a device that changes an auditory signal into infrared light. This signal is delivered to an infrared receiver via light-emitting diodes. The signal is then converted back into auditory energy. 2. Nineteen percent of elders at the Day Care Center for the Elderly who participated in the survey expressed an interest in using an IRLD if it were made available to them. More than half of the clients in this group were successful in using the listening device. 3. The application of an IRLD can add a dimension of independence to the lives of older adults. For those individuals who are unable to operate a conventional hearing aid, an IRLD can offer the benefits of amplification in a form that may be easier to comprehend and operate. PMID- 8345144 TI - [An experimental animal model for inducing fetal distress during pregnancy]. AB - In order to try to understand and treat efficiently pathology in the human pregnant woman the authors have carried out experimental work on animals. Twenty four pregnant ewes with a single fetus were operated on in the last trimester of pregnancy. Fetal distress was provoked by injecting microspheres into the aorta beneath the renal arteries via the femoral route. The first results in terms of survival, by chemical and Doppler measurements were very encouraging. The operation itself was not a significantly disturbing factor, but the injection of microspheres did cause fetal distress. This experiment should be continued. PMID- 8345145 TI - [A new approach to the axilla: functional axillary lymphadenectomy and padding]. AB - Axillary lymph node dissection, which is now mandatory in the conservative breast cancer surgery and classically involves Berg's two lower levels, is burdened with numerous complications. In 1988 and 1989, two technical modifications were introduced and are described here: padding of the axilla as preventive treatment of postoperative lymphocele and, more recently, functional axillary lymphadenectomy (FAL) in which the medial cutaneous nerve of the arm, the two perforating intercostal nerves and above all the lateral thoracic pedicle (external mammary artery and vein) are spared. These two technical innovations, more respectful of anatomy, are aimed at reducing the morbidity of conservative breast cancer at a time when detection enables breast cancers to be treated at an increasingly early stage, which results in a increase of negative axillary dissections. The postoperative period is simplified (no drainage, immediate mobilization), and the hospital stay is reduced to 2 days. Complementary treatments can thus be started early on, without any functional or cosmetic damage while the number of lymph nodes removes remains the same as in the conventional axillary dissection technique. The authors describe the operative procedures and analyse the 100 cases of conservative breast cancer they have treated with padding and FAL. These two technical modifications are now systematically used by them in the management of breast cancers. PMID- 8345146 TI - [Metastasis of breast cancer to a uterine leiomyoma]. AB - The authors report a case of metastasis of cancer from the breast in a uterine leiomyoma. The metastases into the body of the uterus from extragenital cancers are rare. If they occur they are usually in the myometrium where they are asymptomatic and where the diagnosis is difficult, or in the endometrium where the diagnosis can be made by biopsy after curettage. A few rare cases of metastases in uterine leiomyoma have been reported in the literature. They can be the cause of very sudden increase in size of fibroids with compression of the pelvic organs. PMID- 8345147 TI - [Cancer of the ovary and the hormonal context]. AB - Screening for ovarian cancer can only be worthwhile if it is applied to a population at risk. Recent studies show that there is a significant lowering of the risk for cancer of the ovary after all contraceptive preparations containing oestrogens and progestogens have been used. The longer these preparations are used the greater the protection for the user and this protection continues for a long time after treatment has stopped. One finds, in truth, that if the ovary is put functionally at rest whether it is because ovulation has been stopped by pregnancy or by oral contraception or by a premature menopause, or late puberty, the ovaries are somewhat protected from cancer. On the other hand, women whose reproductive life is long without being interrupted as far as ovarian function is concerned, have a higher risk of developing cancer and, therefore, would be worthwhile screening. Furthermore, on the other hand the problems of stimulating the ovaries when treating for sterility must be considered in the relationship to the possibility of provoking cancer of the ovary. A better knowledge of the hormone status would make it easier to decide what cases should be screened for epithelial cancer of the ovary so that the prognosis can be less disastrous than it is. PMID- 8345148 TI - [Endometrioid adenofibroma of the ovary. An anatomo-clinical case report]. AB - Endometrioid adenofibromas are rare tumours of the ovary characterised by proliferation of endometrial type glands without any particular atypical cell structure, within a dense and thick stroma. We report a case of such a tumour which showed an outline of stromal luteinisation. PMID- 8345149 TI - [Benign teratoma of the ovary with fistula to the uterus]. PMID- 8345151 TI - [Management of a short femur discovered via ultrasound in utero. Prenatal diagnosis of Stuve-Wiedemann syndrome]. AB - The authors report a case of familial Stuve-Wiedemann syndrome where the diagnosis was made in utero. Following this case the authors discuss the management of short femur discovered by ultrasound. The analysis of the morphology, the ultrasound appearance and the radiographic appearance (X-ray of the uterine contents) may make it possible sometimes to diagnose the syndrome. An important element is a study of the genealogy to discover the way in which a large number of these bone diseases are transmitted. The prognosis for life is very variable according to the severity of the syndrome. PMID- 8345150 TI - [Antenatal diagnosis of toxoplasmosis. 176 case reports]. AB - OBJECTIVE: To determine the value of antenatal diagnosis of congenital toxoplasmosis by ultrasound guided aspiration of cord blood for testing. MATERIAL: This is a prospective study of 176 cases. As well as obtaining fetal blood and amniotic fluid the searched for specific IgM and A as well as culturing for the parasites on human fibroblasts and inoculation of mice, as well as researching them for non-specific signs of fetal infection. 149 children were able to be followed up one year after birth. RESULTS: 15% of the children (22/149) were infected with toxoplasmosis. 11 out of these were diagnosed positive antenatally. For the 11 others the diagnosis of fetal infection could only be made after birth, but the non-specific signs made it possible to expect early that they had been contaminated. 59% (13/22) had latent toxoplasmosis which only showed up after a mean interval of 34 months after birth. 41% (9/22) had clinical and/or paraclinical signs of toxoplasmosis (mainly unilateral non macular chorioretinitis and intracranial calcifications) but they are well after a follow-up period averaging 30 months. COMMENTARY: Ultrasound alone, when it shows up fetal abnormalities, can make the diagnosis of the severity of the condition. The role of taking fetal specimens is to make clear those infants that are infected because of specific signs, and to find those fetuses which are at high risk because of non-specific signs in order to improve the management of the cases. This development has made it possible to avoid carrying out a large number of unnecessary terminations of pregnancy and has resulted in the birth of affected infants that had no functional sequelae from the infection. PMID- 8345152 TI - [Toxoplasmosis and pregnancy: is it possible to simplify the diagnostic procedures?]. AB - About 1% of all pregnancies in France are complicated by a primary infection with toxoplasmosis. The risk for the fetus being affected increases during the pregnancy but the seriousness of the effect on the fetus becomes less with more advanced pregnancies. Treatment of the mother using Spiramycin have been proven to be efficient, lessening the risk for the fetus being affected. The diagnosis of the fetus being affected rests on a whole bundle of presumptive evidence culled from non-invasive methods and invasive methods which are not without risk. (Direct or over-enthusiastic diagnostic techniques or none at all). We have studied a series of 101 primary infections with toxoplasmosis for which we have not carried out any invasive diagnostic techniques. The long term results in 77 infants show no difference in fetal morbidity and better results as far as mortality are concerned. We therefore propose simplifying the diagnostic approach in cases of primary infection with toxoplasmosis during pregnancy. PMID- 8345153 TI - [Antiphospholipid syndrome. Proposition for management]. AB - Antiphospholipid antibodies (antiprothrombinase and anticardiolipin) carry with them for mothers the risks of repeated fetal loss and of disorders of the blood clotting mechanism both before and after delivery. All the same screening does not have to be carried out routinely but should be reserved for patients who have already lost one fetus (intrauterine death after 12 weeks of amenorrhoea) and/or venous or arterial thrombosis. The diagnosis depends on a strict methodology and strict criteria for making a positive diagnosis. The treatment of these antibodies (with corticosteroids and intravenous immunoglobulin) or the prevention of possible thrombotic complications (using platelet antiaggregation/heparin) has to be decided taking into account the level of antibodies, previous obstetric and thrombotic history and the lupus symptomatology as shown by the patients. The overall success rate of treatment is between 53 and 81%. PMID- 8345154 TI - [Pathological Doppler uterine readings when the placenta is laterally situated]. AB - We carried out a retrospective study on 96 patients whose uterine waveforms were abnormal, in order to determine if a laterally located placenta further increased this risk. Our population was separated into 2 groups (75 women with a laterally located placenta, 21 with a centrally located placenta). We have found a significant difference between ipsi placental uterine blood flow velocity and contralateral placental blood flow velocity when the placenta is located laterally, where as the 2 arteries are similar when the placenta has a central location. The following factors were used to compare the two groups: the patient's previous obstetric record and the incidence of hypertensive disorders and fetal distress. In the group with laterally located placentas, the incidence of complications in previous pregnancies was higher, hypertension was more frequently serious or presented complications, fetal distress and cesarean sections were more frequent as was IUGR. All cases of intrauterine death were found in the group with laterally located placentas. In determining the predictive value of the "laterally located placenta" test, we found in the centrally located placenta group that hypertensive disorders were often less serious and less frequently complicated by albuminuria, that the outcome of pregnancy disorders was less serious for the fetus, and that the neonate was less hypotrophic. No incidence of intrauterine death was recorded for the centrally located group. Placental laterality significantly increases both the frequency and the seriousness of fetomaternal hypertensive disorders. PMID- 8345155 TI - [Congenital arteriovenous malformation of the internal iliac artery discovered during pregnancy]. AB - We report a case found at the start of labour because of the presence of a "tumour praevia". Ultrasound, Doppler and tomodensitometric examination carried out after caesarean section confirmed the vascular origin of this lesion. Arteriography made it possible to decide the pattern of this arteriovenous malformation which was occurring in several branches of the left internal iliac artery. It was not possible to obliterate it completely by selective arterial embolisation, so it was removed surgically a few months later. Little is known about the complications that occur because of these arteriovenous malformations in pregnancy and during delivery. There is the theoretical risk that spontaneous rupture will occur in pregnancy but this does not justify terminating the pregnancy. It is better to carry out caesarean section because the tumour can obstruct delivery and may rupture as well as causing delay in labour. The treatment for these lesions is sometimes difficult and complex and one has to decide whether to preserve the uterus or not. Selective embolisation and pre operative embolisation followed by surgical removal of dysplasic tissue are the therapies of choice. PMID- 8345156 TI - [Endoscopic surgery during pregnancy. A case report of cholecystectomy]. AB - Pregnancy used to be considered a contraindication for endoscopic surgery of the digestive tract. We report a case of cholecystectomy carried out laparoscopically for complicated gall stones in a woman who was 14 weeks pregnant. There was no post-operative maternal or fetal morbidity. The mother carried on the pregnancy to term normally and gave birth to a normal infant. The same results have been reported in the literature for three other cases of cholecystectomy and six of appendicectomy. The sole technical precautions that had to be undertaken were in introducing and placing the trocars, taking into account the size of the uterus. There has been no scientific proof that CO2 is toxic for the fetus. Clinical practice shows that endoscopic surgery is possible without any obstetrical risk including thrombo-emboli, nor specific sepsis occurring in any of the three trimesters of pregnancy. The advantages of the endoscopic approach are that there is less post-operative pain and therefore less need to take analgesics. There are no complications because of an abdominal wound and the patient can both feed and walk about immediately after the operation with a reduction of the time spent in hospital. There is probably less risk of aborting when compared with classical laparotomy. The endoscopic route can be chosen when surgery is needed in the digestive tract during pregnancy. PMID- 8345157 TI - [Prohibition concerning gifts to the medical corps]. PMID- 8345158 TI - Aggression in the demented patient: a double-blind study of loxapine versus haloperidol. AB - Aggression is common in dementia, with devastating social consequences. While high or low potency neuroleptics are the usual treatment of choice, they have been shown to yield inconsistent behavioral improvement and significant iatrogenic disability. This double-blind study was undertaken with aggressive demented patients to assess the efficacy and safety of a mid-potency neuroleptic, loxapine, in comparison to the more commonly prescribed high potency drug, haloperidol. Using an optimizing dosage regime, the outcome variables studied were aggression frequency and the number and nature of emergent side effects. Results demonstrated no significant difference regarding efficacy, but significantly fewer side effects with loxapine administration. The clinical and theoretical implications of these findings are discussed. PMID- 8345159 TI - Responders and non-responders to bifemelane hydrochloride in Alzheimer-type and multi-infarct dementia. AB - Although metabolically active compounds sometime attenuate cognitive deficits of dementia patients, this mechanism has not been discussed or investigated. We hypothesized that these compounds improve cognitive disorders not by directly acting on this cognitive function, but by increasing the arousal level. Based on this hypothesis, we investigated the change of arousal levels and the improvement of intellectual functions in 10 patients with Alzheimer-type dementia (ATD) and 10 patients with multi-infarct dementia (MID) before and 3 months after pharmacotherapy using bifemelane hydrochloride. For each patient, a psychological test battery was carried out and the arousal level was evaluated using the frequency of rapid eye movements in the electro-oculogram (EOG) and the frequency analysis of electroencephalogram (EEG) before and after the treatment. Evaluation of the cognitive improvement was made and eight out of the 20 patients were regarded as responders to the treatment. The frequency of small rapid eye movements (SREM) in the EOG increased significantly only in responders and the rate of change in SREM appearance in responders was significantly different from that in non-responders. This finding suggests that a part of the intellectual improvement in ATD and MID results from the increased level of arousal. PMID- 8345160 TI - Three-year follow-up of patients with panic disorder after short-term treatment with alprazolam and imipramine. AB - Fifty-five patients with moderate to sever panic disorder were treated for 9 weeks with alprazolam or imipramine and were then, except for one patient who had committed suicide, re-examined after on average 3 years of treatment. At follow up most patients (74%) did not suffer from panic attacks at all. In the beginning of the study 87% exhibited phobic avoidance behaviour but after 3 years 68% no longer revealed phobic behaviour. At follow-up 28% of the patients were no longer having psychotropic drug treatment and 20% were completely free of overt psychopathology. No tolerance phenomena were associated with the long-term medication applied in the study. PMID- 8345161 TI - Tryptophanemia and tyrosinemia in adolescents with impulsive behavior. AB - Tryptophan (TRP) and tyrosine (TYR), respectively the circulating precursors of the central serotonergic (5-HT) and catecholamine systems, were measured in eight adolescents with impulsive behavior regardless of the exact type of disorder. The 6 week study period included weekly blood sampling and clinical evaluation. The ratios of TRP and TYR to large neutral amino acids (LNAA), which indicate the availability for the synthesis of neurotransmitters, were calculated. Comparison of results with eight hospitalized controls of the same age (12.5 to 18 years) revealed lower total TRP levels in four adolescent patients, a lower TRP/LNAA ratio in three adolescents, and a lower free TRP concentration in six adolescents with discretely enhanced albuminemia. A slight increase in TYR and the TYR/LNAA ratio was noted in nearly all of the adolescent patients. Despite the heterogeneity of individual biological results, the impulsive behavior subjects in this study seemed to present abnormalities in neurotransmitter precursors. PMID- 8345162 TI - Evidence for a defective platelet L-tryptophan transport in depressed patients. AB - The kinetic characteristics of platelet L-tryptophan uptake were investigated in 23 untreated depressed patients and 18 healthy volunteers. A significant increase of 50% in the apparent Michaelis constant (Km) was observed in depressed patients compared with controls, without significant change in the maximal velocity (Vmax). After 1 month of successful antidepressant treatment the mean Km value decreased significantly and reached the control value. This result raises the possibility that the decrease in platelet tryptophan uptake affinity is a state dependent marker for depression. It is likely that the transport alteration results in a decrease in platelet tryptophan accumulation. The effect of this peripheral membrane defect on brain serotonin function is discussed. PMID- 8345163 TI - Fluoxetine's spectrum of action in premenstrual syndrome. AB - This study extends our previous report of the efficacy and tolerability of fluoxetine in severe premenstrual syndrome (PMS), describes which aspects of the disorder are responsive to such treatment, and assesses the relationship between steady-state drug level and clinical outcome. Twenty-one women with documented PMS satisfied criteria for late luteal phase dysphoric disorder (DSM-III-R) and accepted the offer of a double-blind, randomized crossover trial of fluoxetine hydrochloride 20 mg/day vs placebo. Symptom severity was measured with daily self rating, monthly premenstrual assessment forms and psychiatric interviews after 3 months each of baseline, placebo and fluoxetine treatment. Compared with an inconsistent placebo response, fluoxetine produced marked improvement in 15 of 16 women completing the trial, eight showing virtually complete remission of PMS symptoms. Fluoxetine's efficacy extended over a range of affective, physical and behavioural symptoms; its superiority obtained whether it preceded or followed placebo. Three women withdrew due to adverse effects of fluoxetine, and 10 of 16 completing the trial reported at least one adverse effect of this agent. Compared with placebo, fluoxetine produced more (but usually transient) insomnia, sweating, gastrointestinal and menstrual disturbance. Plasma levels of fluoxetine and its active metabolite were not reliably associated with efficacy nor with side effects. Serotonergic agents appear to have considerable promise in treating a range of symptoms in women with severe PMS. PMID- 8345164 TI - DNA hybridization techniques and their application to the diagnosis of infectious diseases. AB - Several commercial DNA probe assays are widely used in clinical microbiology laboratories. These include culture-confirmation assays for Mycobacterium species, which are recommended by CDC because they are both rapid and accurate, and culture-confirmation assays for N. gonorrhoeae. Probe assays for direct detection of N. gonorrhoeae and C. trachomatis are also widely used in public health and large reference laboratories. In many cases, the probe assays have decreased the time to identification of positive cultures and improved detection of these pathogens because they do not depend on the presence of viable organisms to achieve a positive result. Nucleic acid amplification assays hold promise for the rapid detection and identification of many infectious agents. PCR using universal primers enables researchers to identify new agents of disease that cannot be cultured in vitro; more importantly, PCR provides a method for detecting the presence of any bacterial species, including common organisms, in normally sterile body fluids, such as blood and cerebrospinal fluids. The use of such primers may well give PCR the broad-based approach needed to identify organisms in the clinical microbiology laboratory of the future. PMID- 8345165 TI - New developments in the diagnosis of viral diseases. AB - Major technical advances have occurred, especially in the last 5 years, in the laboratory diagnosis of viral infections. Immunologic detection of immediate early antigens in specimens such as bronchoalveolar lavage fluid and blood inoculated into shell vial cell cultures, particularly for herpesvirus (cytomegalovirus, herpes simplex virus, varicella-zoster virus), has provided results 16 to 48 hours after inoculation rather than the several days required for recognition of cytopathic effects in conventional tube cell cultures. Similarly, cytomegalovirus viremia can be detected directly by immunostaining of peripheral blood leukocytes with commercially available reagents the same day the specimen is submitted to the laboratory. Single-test membrane immunoassays have provided rapid (15 minutes) detection of viral antigens (respiratory syncytial virus, rotavirus, influenza virus type A). In the near future, diagnostic virology laboratories will be expected to monitor viral strains for susceptibility to the growing list of antiviral drugs. Amplification of nucleic acid sequences of viruses from cerebrospinal fluid or tissue, which generally does not yield isolates by conventional diagnostic techniques, has added a new dimension to the laboratory diagnosis of viral infection. PMID- 8345166 TI - Laboratory diagnosis of human immunodeficiency virus infection. AB - HIV infection and AIDS will continue to grow as a major medical and social problem. The incidence of heterosexual transmission is rising, and it will become increasingly difficult for physicians and counselors to assess an individual's risk of infection. In coming years, physicians can expect to see patients who are infected, but whose risk may not be apparent, and who may not present with conditions immediately suggestive of their infection. The majority of these patients may not even suspect they are infected. Many of the tests currently available for diagnosing HIV infection are very good. They are both highly sensitive and highly specific and their predictive values are good when their limits are understood. But, as HIV infection expands to an ever larger number of women and children and as the ability to sharply define risk groups fades, demand for a broader range of tests that can reliably confirm infection and are easy to perform can only increase. We have attempted to describe some of the common serologic tests currently used to diagnose HIV infection and some of the limitations of these tests. We also have pointed out that criteria used by laboratories for interpreting tests such as the Western blot may not always be uniform, and physicians should know the criteria used by their reference laboratory and the quality control measures taken. We also have attempted to describe some of the tests available to detect the virus, its genes, or its gene products. PCR and other rapidly evolving gene amplification techniques hold great promise as highly sensitive and specific tests for the diagnosis/confirmation of HIV infection. As with the serologic tests, it is important for those who may use these tests to understand their value as well as their limitations. PMID- 8345167 TI - Blood cultures. AB - Bacteremia and fungemia are encountered commonly and are associated with significant morbidity and mortality. Laboratory detection is therefore of paramount importance. Principles of successful blood culturing, clinically important technical issues, manual and automated detection systems, and interpretation of culture results are reviewed in this article. PMID- 8345168 TI - The microbiologic aspects, including diagnosis, of beta-hemolytic streptococcal and enterococcal infections. AB - Basic principles concerning the collection, transport, and processing of clinical specimens for the detection of Streptococcaceae are given. Identification of beta hemolytic streptococci (S. pyogenes, S. agalactiae, Lancefield group C and G streptococci, S. anginosus) and enterococci is based on the careful observation of colony morphology and hemolytic pattern on sheep blood agar plates; subsequent genus or species confirmation is achieved by rather simple biochemical or enzymatic tests and by detection of streptococcal cell wall carbohydrate antigens (Lancefield grouping). Rapid antigen tests for the detection of group A and B streptococci directly from pharyngeal and vaginal swabs, respectively, are highly specific, thus allowing an immediate antibiotic therapy in patients with a positive test result. The reported sensitivities of these nonculture tests are too low to exclude streptococcal colonization or infection, however. The elucidation of the genetics of some major virulence factors of group A and B streptococci has contributed to knowledge of their association with disease, and molecular techniques have supplemented the traditional (mostly culture and serologic) methods for an improved understanding of the epidemiology and pathogenesis of streptococcal infections. Recently employed examples include the M protein gene typing of group A streptococci by oligonucleotide probes and the use of PCR assays for the detection of the genes encoding for the pyrogenic exotoxins. Restriction enzyme endonuclease digestions of bacterial DNA in association with DNA fragment separation by conventional or PFGE have been applied successfully to several species of Streptococcaceae (e.g., S. pyogenes, S. agalactiae). Enterococci are important pathogens in the hospital setting, exhibiting high morbidity and mortality rates in bacteremic patients with severe underlying disease. Molecular typing methods have clearly confirmed their potential to be nosocomially transmitted. E. faecalis and E. faecium still account for the majority of human infections, but some of the newer enterococcal species (at present 19 species are recognized) have been encountered as well. The definitive species identification of enterococci requires the performance of an array of biochemical tests. The increasing antimicrobial resistance of enterococci, including high-level resistance to penicillins and aminoglycosides and occasionally also to glycopeptides, has hampered standard therapeutic regimens. All enterococci isolated from serious infections should be tested for high-level gentamicin and streptomycin resistance by one of several methods evaluated; beta-lactamase production (primarily found in E. faecalis) is reliably detected by the nitrocefin test.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345169 TI - Current perspectives on anaerobic infections: diagnostic approaches. AB - This article discusses when to look for anaerobes, anaerobic infections as clues to other problems in patients, and underlying clinical conditions as clues to the nature of anaerobic infections. Diagnostic approaches, identification methods, and susceptibility testing are reviewed. PMID- 8345170 TI - The role of the clinical microbiology laboratory in the management of Clostridium difficile-associated diarrhea. AB - Nosocomial diarrhea due to infection with C. difficile is a major health care problem, causing 20% to 30% of institutionally acquired diarrhea and affecting up to 8% of hospitalized patients. The clinical microbiology laboratory should be able to provide both diagnostic and epidemiologic services for institutions where this disease occurs. Diagnostic testing includes culture for isolation of toxigenic C. difficile and detection of either toxin A or B from stool specimens. Epidemiologic services include providing appropriate media and specimen preparation for surveillance activities and performance of accurate typing of C. difficile strains when necessary to determine organism relatedness for development of effective infection control practices. PMID- 8345171 TI - Diagnosis of ventilator-associated pneumonia. AB - Ventilator-associated pneumonia is a frequent complication of mechanical ventilation, and it carries a significant added mortality. Proper recognition and treatment of pneumonia are associated with improved outcome. Clinical manifestations of pneumonia, chest radiograph findings, and routine analysis of the tracheal aspirate are inadequate, alone or in combination, in diagnosing pneumonia. This article discusses the methodologies that are presently available for diagnosing pneumonia in ventilated patients. Correct use of these techniques helps the clinician to establish a diagnosis with a high degree of reliability and facilitates the rational use of antibiotic treatment. PMID- 8345172 TI - Microbiologic diagnosis of ventilator-associated pneumonia. AB - Specific etiologic diagnosis in ventilator-associated pneumonia is critical to optimal patient care, and a wide array of microbiologic procedures are available to aid in diagnosis. In bacterial infection, direct stains, particularly the Gram stain, provide rapid presumptive information, and cultures provide definitive identification. Specimen selection is critical; endotracheal or ordinary bronchoscopic aspirates provide nonspecific information, and quantitative analysis of protected specimen brushes or bronchoalveolar lavage provides more accuracy. Specialized procedures for other groups of organisms, such as Chlamydia, Legionella, mycobacteria, fungi, and viruses, also may be indicated in some cases. PMID- 8345173 TI - The laboratory diagnosis of mycobacterial diseases. AB - Recent developments in diagnostic mycobacteriology are surveyed with emphasis on laboratory capabilities relevant to the more rapid and accurate detection and identification of mycobacterial pathogens. Some terminologic problems are reviewed, and some newly recognized mycobacterial pathogens are discussed. Newer methodologies presented in some detail include the radiometric technique for detection, identification, and susceptibility testing of mycobacteria, and the use of DNA probes for identification of mycobacterial species and species complexes. The utility of other developing methodologies, such as polymerase chain reaction technology, analysis of body fluids for tuberculostearic acid, and the use of ELISA are also assessed. PMID- 8345175 TI - Antimicrobial susceptibility testing of bacteria that grow aerobically. AB - This article focuses on susceptibility testing methods for aerobic and fastidious bacteria that may be tested using standard dilution or agar diffusion methods. Also discussed are those bacteria that may be tested by use of an automated or nontraditional methodology. PMID- 8345174 TI - Legionella and the clinical microbiologist. AB - Legionella species are important etiologic agents of sporadic and epidemic community-acquired and nosocomial respiratory disease. The list of species continues to expand, and tools for classification and characterization of isolates have become increasingly sophisticated. These organisms are associated with aquatic habitats and are transmitted by aerosol or direct contact. Bacterial culture is the cornerstone of laboratory diagnosis. Careful surveillance of infections is important, because infections potentially can be prevented. PMID- 8345176 TI - Problems with detection of beta-lactam resistance among nonfastidious gram negative bacilli. AB - The single most important aspect of any susceptibility test is the accurate detection of resistance, because resistance carries a strong prediction of therapeutic failure. However, the accurate detection of resistance has been difficult in tests performed with gram-negative organisms producing certain beta lactamases and in tests with the new beta-lactam drug/beta-lactamase inhibitor combinations. These problems are due to limitations in the design of studies performed to establish test parameters, and these problems can be avoided if a new predictor panel approach is used. This, coupled with the use of special tests to detect resistance mechanisms, could optimize the accurate identification of beta-lactam resistance in gram-negative bacteria. PMID- 8345177 TI - Detection of methicillin-resistant staphylococci. AB - Susceptibility tests commonly used in the clinical laboratory for detection of methicillin-resistant strains of staphylococci are discussed. The biochemical and genetic basis of methicillin resistance, including heterogeneous expression of resistance, is summarized. The conditions that can affect results of disk diffusion, broth dilution, and agar screen tests and sensitivity and specificity of these tests are reviewed. DNA detection methodologies, which, with their greater accuracy, may replace susceptibility testing, also are discussed. PMID- 8345178 TI - Antifungal susceptibility testing. Current state of technology, limitations, and standardization. AB - In parallel with the escalating incidence of serious, invasive fungal infections in the immune-compromised host has been the development and use of new, potentially efficacious antifungal agents as well as recognition of both primary and secondary resistance to such drugs by the etiologic mycotic agents. These findings have generated considerable enthusiasm for a reproducible and standardized means for the laboratory evaluation of antifungal drugs. For over a decade, global investigations have ensued in the hope of generating laboratory methods analogous to those used for antibacterial drugs that may predict the optimal therapeutic choice for clinicians treating mycoses. This article reviews the background, history, and development of in vitro antifungal susceptibility efforts, details the problems inherent in this area of laboratory medicine/infectious diseases, and assesses the contemporary aspects of standardization. PMID- 8345179 TI - Bactericidal testing. AB - Recognition of the importance of bactericidal activity in certain clinical settings has generated a great deal of interest in bactericidal testing. Indeed, bactericidal testing can be of great use in a number of settings, but it also has the potential for being overutilized. Moreover, there are biologic and technical pitfalls inherent in bactericidal testing. This article addresses these issues and summarizes the progress toward standardization of these methods. Thoughtful and deliberate application of standardized bactericidal testing should make this controversial test much more useful in the future. PMID- 8345180 TI - The good old days--past, present, and future. PMID- 8345181 TI - Increasing the immunogenicity of protein antigens through the genetic insertion of VQGEESNDK sequence of human IL-1 beta into their sequence. AB - The immunogenicity of two recombinant protein Ag containing the immunostimulatory sequence of human IL-1 beta 163-171 (VQGEESNDK) genetically engineered into their structure has been evaluated. The IL-1 beta sequence was inserted into the loop between alpha helices D and E of recombinant human ferritin H chain and into the hypervariable region of recombinant flagellin from Salmonella muenchen. The chimeric proteins were injected into mice and the level of humoral immune response developed against the native proteins was assessed by measuring the number of Ag-specific plaque forming cells/spleen or as the level of serum IgG response. The response was compared to that of mice receiving injections with wild-type protein Ag not containing the VQGEESNDK sequence or with hybrid constructs containing unrelated foreign peptide sequences of the same length. A significantly higher immune response was observed in mice immunized with chimeric constructs containing the human IL-1 beta 163-171 sequence. These data suggest that the insertion of the VQGEESNDK sequence may prove useful to increase the immune response against poorly immunogenic recombinant proteins. PMID- 8345182 TI - Regional specialization of the mucosal immune system. Intraepithelial lymphocytes of the large intestine have a different phenotype and function than those of the small intestine. AB - Intraepithelial lymphocytes (IEL) are found in both the small and the large intestine. We demonstrate that there are a number of striking phenotypic and functional differences between the two populations of IEL isolated from mice. In the large intestine, the majority of IEL express the alpha beta TCR, and among these TCR-alpha beta+ lymphocytes, CD4+ cells are as prevalent as CD8+ cells. In contrast, in the small intestine, most of the TCR-alpha beta+ IEL express CD8, and an increased percentage of cells express TCR-gamma delta. In addition, most TCR-gamma delta+ IEL isolated from the large intestine (LI-IEL) are CD4- CD8- cells, as compared to TCR-gamma delta+ IEL isolated from the small intestine (SI IEL), which are predominantly CD8+. Furthermore, CD2 and the lymph node homing receptor, L-selectin, are expressed by most LI-IEL but not by SI-IEL. Furthermore, LI-IEL have much less cytolytic activity than SI-IEL. These data suggest that LI-IEL are a distinct population of lymphocytes that may have a different immunologic role than that of SI-IEL. PMID- 8345183 TI - Expression of merosin in the thymus and its interaction with thymocytes. AB - Merosin is a 700 kDa multichain protein that has several properties in common with laminin, one of the major extracellular matrix proteins present in basement membranes. Both contain B1 and B2 light chains, but merosin has a distinct M chain compared with the laminin A-chain. Merosin is present in the basement membrane of placenta, striated muscle, and peripheral nerve. Using the RT-PCR assay, we demonstrate that merosin, but not laminin, is also expressed in the thymus. A partial cDNA sequence of the mouse merosin M-chain was 88% identical to the human M-chain, and the deduced amino acid sequences were 95% identical. 18 24% of adult mouse thymocytes bound to human merosin in vitro. Mg2+, but not Ca2+, was essential for binding. Binding was inhibited by antibodies recognizing VLA alpha 6 or beta 1, suggesting that the VLA-6 integrin is a merosin receptor. An anti-beta 4 integrin subunit mAb failed to inhibit binding, suggesting that the alpha 6 beta 4 integrin was not involved. Thymocytes were fractionated into immature and mature populations based on their expression of the heat stable antigen, recognized by the J11d mAb. Virtually all thymocytes expressed VLA-6, but only immature thymocytes (J11d+) bound to meroson. PMA treatment did not significantly increase the binding of J11d+ thymocytes nor did induce binding in the mature J11d- population. In constrast, both splenic T cells and unseparated lymph node cells showed enhanced binding to merosin after PMA stimulation. The expression of merosin in the thymus and its selective interaction with immature thymocytes suggest that thymocyte-merosin interactions may play a role in T cell development. PMID- 8345184 TI - Urtica dioica agglutinin. A superantigenic lectin from stinging nettle rhizome. AB - Urtica dioica agglutinin (UDA) is an unusual plant lectin that differs from all other known plant lectins with respect to its molecular structure and its extremely low specific agglutination activity. We recently reported that this small lectin (8.5 kDa) is a T cell mitogen distinguishable from classical T cell lectin mitogens by its ability to discriminate a particular population of CD4+ and CD8+ T cells as well as its capacity to induce an original pattern of T cell activation and cytokine production. The mechanism by which UDA activates T cells was investigated and compared with the conventional T cell mitogen Con A and the known superantigen staphylococcal enterotoxin B. Our data show that T cell proliferation induced by UDA is strictly dependent on AC expressing MHC class II molecules but is not MHC restricted. This proliferation can be partially inhibited by anti-I-A or anti-I-E mAb and completely blocked by a mAb recognizing monomorphic determinants on the Ia molecule. UDA indeed binds to specific carbohydrate structures present on class II molecules. UDA-induced T cell stimulation is dependent on TCR recognition of the unprocessed intact molecule in association with various Ia molecules. T cell response to UDA is clonally expressed and correlates with particular TCR V beta gene families usage. This stimulation leads to a sixfold enrichment of V beta 8.3+ T cells within 3 days. Therefore, UDA appears to use the same molecular mechanism as structurally unrelated bacterial or retroviral superantigens and we propose that this lectin is a superantigen. UDA, which is not a pathogenicity factor, could provide a useful probe for the analysis of T cell activation by superantigens. PMID- 8345185 TI - Early signals in alloantigen induced B-cell proliferation. Comparison between B cell triggering by intact allogeneic cells and solubilized alloantigen. AB - Stimulation of B cells from BALB/c with allogeneic lymphocytes from C57BL/6 mice resulted in a slight increase in cytosolic Ca2+ but in the absence of proliferative response. Immunization of BALB/c mice with C57BL/6 total lymphocytes resulted in an enhancement of cytosolic Ca2+ and of B cell proliferation. Phosphatidylinositol specific phospholipase C was activated immediately after allogeneic stimulation as deduced by the concomitant rise in inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. Translocation of protein kinase C from the cytosol toward the membranes paralleled the elevation in cytosolic free Ca2+. Activation of BALB/c B cells with solubilized alloantigen from the plasma membrane of C57BL/6 lymphocytes produced qualitatively the same early responses as the treatment with allogeneic cells, although quantitatively more intense. Concerning protein kinase C, an important degradation was observed in these conditions. Soluble alloantigen failed to promote B cell proliferation, being observed when cells were costimulated with a low concentrations (2 ng/ml) of phorbol 12,13-dibutyrate before alloantigen addition. Analysis of the molecular weight of the active fraction of the solubilized alloantigen revealed the presence of a 51 kDa protein that mimicked all properties of the alloantigen preparation. This molecule was also recognized in Western blot by an anticlass I mAb and by the sera of immunized animals. A putative MHC class I antigen is proposed as the nature of the active molecule, and its interaction with specific membrane Ig on the B cell is analyzed. Although the results fit with a cellular response mediated through membrane Ig, the involvement of other B cell surface molecules interacting with the alloantigens cannot be disregarded. PMID- 8345186 TI - Superantigen-driven peripheral deletion of T cells. Apoptosis occurs in cells that have lost the alpha/beta T cell receptor. AB - Injection of lymphoid cells expressing minor lymphocyte-stimulating antigen-1 (Mls-1a) induces tolerance to the superantigen, and partial deletion of Mls-1a reactive T cells. We have identified a transient population of T cells that have lost the alpha/beta T cell receptor at the time when Mls-1a-reactive T cells start to disappear during the process of tolerance induction. Apoptosis was directly demonstrated in this TCR-alpha/beta negative T-cell population. This indicates a peripheral T-cell deletion pathway, characterized by TCR down regulation, apoptosis, and clonal deletion. The consequence of Mls-1a-induced TCR down-regulation appears to be different in CD4+ cells and in CD8+ cells. Although most of the CD4+ cells that have lost TCR expressing alpha- and beta-chains appear to be undergoing apoptosis, many of their CD8+ counterparts may be able to re-express the Ag receptor. This argues for the involvement of coreceptors in the induction of apoptosis during peripheral deletion. PMID- 8345187 TI - Wasting, ischemia, and lymphoid abnormalities in mice expressing T cell-targeted human tumor necrosis factor transgenes. AB - To evaluate the biologic potential of T cell-specific TNF production in vivo, we have generated transgenic mice constitutively expressing TNF in their T cell compartment. This was achieved by placing a wild-type or a 3'-UTR modified fragment of the human TNF gene under the influence of the T cell-specific, locus control region of the human CD2 gene. Transgenic mice that express human TNF mRNA in T cells develop marked histologic and cellular changes locally in their lymphoid organs and a lethal wasting syndrome associated with widespread vascular thrombosis and tissue necrosis. The extent of pathologic changes and their time of onset appear to reflect levels of transgene expression. Thus, transgenic lines that express the transgene at high levels show both lymphoid organ and systemic abnormalities with wasting. In one transgenic line, mice express lower levels of the transgene and develop normally despite pronounced local lymphoid organ defects, confirming in vivo, the differential potential of localized and systemic TNF action. All pathologic changes could be neutralized by the administration of mAb specific for human TNF. These results demonstrate the important role of T cell-specific TNF production in the development of specific pathology and provide a means by which to evaluate the role of TNF in thymocyte development. Transgenic mice that express TNF constitutively in the T cell compartment offer a unique in vivo system by which to analyze the molecular character of systemic vs contact dependent and paracrine modes of TNF action. Furthermore, given the species specific nature of the mouse p75 TNF receptor, it is assumed that the pathology induced by human TNF in these transgenic mice is associated exclusively with p55 TNF receptor signaling. Conceivably, the differential contribution of each of the two TNF receptors in thymus development and TNF-mediated disease can be assessed by comparison of the biologic potential of human vs mouse TNF in the transgenic system developed. PMID- 8345188 TI - Specific V beta T cell subsets mediate the immediate hypersensitivity response to ragweed allergen. AB - T and B cell responses after sensitization to ragweed (RW) were examined in a mouse model in which BALB/c mice were exposed to the allergen by ultrasonic nebulization. Sensitization resulted in the stimulation of an IgE anti-RW response and was paralleled by a rise in IgG1 anti-RW titers. Skin testing for immediate cutaneous hypersensitivity revealed the presence of allergic type I reactions to RW. Sensitization to RW in this way was also associated with the development of increased airways responsiveness as determined by electrical field stimulation of preparations of tracheal smooth muscle. Histologic examination of the airways and the lung indicated the presence of a mononuclear cell infiltrate in the mucosa and submucosa of the airways that was accompanied by an enlargement of local draining lymph nodes of the airways and the lung. T cell populations were analyzed for the frequency of V beta-expressing T cells. Such analysis indicated that RW sensitization stimulated the expression of V beta 8.1+, V beta 8.2+, and V beta 13+ T cells in the local lymphoid tissue and of V beta 8.1+, V beta 8.2+, V beta 8.3+, V beta 9+ and V beta 14+ T cells in the spleen. Co culture of these T cell populations with RW-primed B cells indicated that in the presence of RW, V beta 8.2 T cells stimulated IgE and IgG1 production, whereas the other T cell populations showed a different stimulation profile for Ig isotypes and IgG subclasses. The transfer of V beta 8.2 T cells from sensitized but not from nonsensitized control mice stimulated an allergen-specific IgE and IgG1 response and increased airways responsiveness in naive recipients. These data provide additional support for the pivotal role of specific V beta expressing T cell subpopulations in the stimulation of IgE/IgG1 production and increased airways responsiveness. PMID- 8345190 TI - A hit-and-run system for introducing mutations into the Ig H chain locus of hybridoma cells by homologous recombination. AB - The traditional method of site-specific mutagenesis is to introduce predetermined mutations into an expression vector, which is then transferred to cells so that the relevant gene product and the effects of the mutations can be measured. A problem with this approach is that the expression of the transferred genes varies from transformant to transformant, presumably because the number of vector copies and the site of chromosomal integration vary among transformants. While it should be possible to avoid this variability by mutagenizing the chromosomal gene itself, the labor involved in introducing predetermined mutations by homologous recombination with a mutagenized vector is usually so intense that this has not been the favored method. We describe here a system for introducing mutations into the IgH locus of hybridoma cells. This system greatly reduces the labor that would usually be required to identify and recover the rare recombinants. This is a two-step, so-called "hit-and-run," method, whereby mutations are first introduced into the chromosomal locus by targeted vector integration, after which the vector is excised so as to leave the mutation in the chromosomal target. The first step employs an enhancer trap vector bearing an enhancerless gpt gene; using this vector the frequency of randomly inserted transformants which grow in mycophenolic acid containing selective medium is so low that approximately 25% of the selected transformants have integrated the vector into the IgH locus by homologous recombination. Properly targeted transformants can then be used to derive secondary recombinants that have excised the vector and thus become gpt-. This second step which involves selection of gpt- cells by their resistance to 6 thioxanthine is also efficient, in that approximately 75% of the treated cells have excised the gpt gene by homologous recombination. Overall the labor involved in mutagenizing the chromosomal locus is not much more than is needed to produce the traditional transformants expressing a mutagenized transferred gene. PMID- 8345189 TI - Rapid Il-2-induced adherence of human natural killer cells. Expression of mRNA for cytokines and IL-2 receptors in adherent NK cells. AB - Natural killer (NK) cells selected by IL-2-induced rapid adherence to plastic and called A-NK cells represent a phenotypically and functionally distinct subset of mature peripheral blood NK cells. To further characterize this subset of NK cells functionally, their potential to express mRNA for the IL-2R and various cytokines after IL-2 activation was examined. Highly purified normal human peripheral blood resting NK (R-NK) cells were obtained by negative immunoselection using OKT3 mAb and magnetic beads coated with goat anti-mouse Ig. By two-color flow cytometry, > 90% of these R-NK cells were either CD3-CD56+CD16+ or - or CD3-CD56-CD16+. R-NK cells were activated in the presence of 6000 IU/ml (22 nM) of IL-2 for different periods of time. After 1, 3, 5, or 24 h, plastic-adherent (A) and nonadherent (NA) NK cells were separated and compared for the expression of the IL-2R or cytokine mRNA by in situ hybridization, using 35[S]-cDNA probes. Only low proportions of R-NK cells expressed genes for IL-2Rp55 (16%) or cytokines IL-2 (20%), IFN-gamma (18%), TNF-alpha (16%), and TGF-beta (7%). Thus, the genes for the IL-2Rp55 and these cytokines were not constitutively expressed by most human R-NK cells, and there was no indication that the NK cells used in these experiments were activated in vivo or during the purification procedure. However, larger proportions of R-NK cells showed expression of mRNA for IL-1-beta (35%) and IL-6 (40%), which indicates that genes for these cytokines may be constitutively expressed in a substantial proportion of normal human circulating NK cells. When R-NK cells were incubated in the presence of 22 nM of IL-2 for 1 to 24 h and separated into A-NK cells and NA-NK cells, a large proportion of A-NK cells became positive for IL-2R and cytokine gene expression. In contrast, the proportion of mRNA-positive NA-NK cells was similar or lower than that observed for R-NK cells, with the exception of an increase in TGF-beta.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345192 TI - Role of the Q10 class I regulatory element region 1 in controlling tissue specific expression in vivo. AB - The MHC class I regulatory element (CRE) region 1 has been previously described as a positive cis-acting regulatory element essential for class I gene expression. We have generated transgenic mice (CBA x C57BL/6) with the MHC class I gene H-2Dd driven by two different 400-bp promoter regions of Q10, a nonpolymorphic MHC class I gene expressed in the liver, kidney, and fetal yolk sac. One transgene contained the wild-type Q10 promoter (Q10WT/Dd). The second construct (Q10M3/Dd) had 2 bp substitutions introduced in region 1 of the CRE that reconstituted the CRE inverted repeat present in classical class I genes. Mice containing the wild-type Q10/Dd gene expressed membrane-bound H-2Dd molecules in a tissue-restricted expression pattern similar to that observed for endogenous Q10. In mice containing the mutant construct (Q10M3/Dd), H-2Dd was also expressed in the thymus, a tissue not normally associated with Q10 expression but, surprisingly, the Dd was not expressed in other lymphoid tissues. Furthermore, thymic expression was greatest on double positive (CD4+ CD8+) thymocytes. Thymic Dd expression was correlated with the presence of what appears to be a previously unidentified transcription factor in thymocytes that is capable of interacting with the CRE-inverted repeat. These results show that the mutations in region 1 altered the tissue-specific regulation of the Q10 promoter in vivo, although an intact inverted repeat did not restore the ubiquitous pattern of expression characteristic of classical class I genes. Thus, these results indicate that elements in addition to CRE region 1 in the Q10 promoter region serve to limit ubiquitous tissue expression. PMID- 8345191 TI - Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoietic cell proliferation, differentiation, and functional activation by inducing the expression of specific genes. As part of an investigation of the regulation of gene expression by GM-CSF, we have previously identified a novel murine GM-CSF inducible gene, A1. In this report, we present the complete nucleotide sequence of the A1 mRNA as well as a portion of the 5' flanking region, and describe the expression pattern of the gene. The results demonstrate that A1 is a hemopoietic tissue-specific gene that is expressed in several hemopoietic cell lineages, including T-helper lymphocytes, macrophages, and neutrophils. In murine bone marrow-derived macrophages, A1 gene expression is rapidly and transiently induced by GM-CSF, and the induction was independent of de novo protein synthesis. In addition to GM-CSF, a transient induction of A1 mRNA accumulation was observed in response to LPS in macrophages. This induction is not mediated by IL-1 alpha or IL-6, neither of which stimulate A1. In the myeloid precursor cell line, 32D cl3, A1 gene expression is stably induced during granulocyte colony-stimulating factor stimulated myeloid cell differentiation. The A1 message encodes a predicted polypeptide with an M(r) of 20,024 and no signal peptide. The peptide sequence contains a region of 80 amino acids that shows similarity to bcl-2 and to the recently described bcl-2-related gene, MCL1. These data demonstrate that A1 is a novel early-response gene whose expression is associated with a variety of stimuli and occurs in several hemopoietic cell types. PMID- 8345193 TI - Expression cloning of complementary DNA encoding three distinct isoforms of guinea pig Fc receptor for IgG1 and IgG2. AB - Three cDNA clones encoding the guinea pig Fc receptor for IgG1 and IgG2 (Fc gamma 1/gamma 2 R) have been isolated by an expression cloning strategy using mAb directed against the receptor. When transfected into COS-7 cells, these cDNA induced cell surface expression of the receptor that bound IgG1 and IgG2 antibodies complexed with the Ag. The ligand-binding affinities of these receptors were indistinguishable. Nucleotide sequencing has indicated that one of these clones, Fc gamma 1/gamma 2R-B1, is identical to the previously isolated cDNA clone homologous to the b2 isoform of human Fc gamma RIIB and that of murine Fc gamma RII, encoding a transmembrane glycoprotein containing two Ig-like extracellular domains. Two other clones, Fc gamma 1/gamma 2R-B2 and -B3, are identical to Fc gamma 1/gamma 2R-B1 except for an inframe insertion in the cytoplasmic region. The 48-nucleotide insertion found in Fc gamma 1/gamma 2R-B2 is identical to the first 48 nucleotides of the B3 insert that comprises 132 bp. Based on the size and homology of the inserted sequence, Fc gamma 1/gamma 2R-B2 and -B3 are identified as the homologues of the b1 isoform of human Fc gamma RIIB and that of murine Fc gamma RII, respectively. Reverse transcription and polymerase chain reaction of RNA revealed that macrophages and polymorphonuclear leukocytes expressed preferentially Fc gamma 1/gamma 2R-B1. On the other hand, B lymphocytes expressed all three forms, among which Fc gamma 1/gamma 2R-B2 and -B3 were selectively expressed in LPS-activated B lymphocytes that showed a dramatic increase in the levels of cell surface expression of Fc gamma 1/gamma 2R. These results suggest that the inserted sequences of Fc gamma 1/gamma 2R-B2 and -B3 are important to generate responses specific for B lymphocytes, which may include regulation of cell activation. PMID- 8345194 TI - Priming immunization determines T helper cytokine mRNA expression patterns in lungs of mice challenged with respiratory syncytial virus. AB - Defining the mechanism for the vaccine-enhanced illness associated with respiratory syncytial virus (RSV) is critical for advancing RSV vaccine development. Previous studies in which infants were vaccinated with formalin inactivated alum-precipitated whole virus did not protect from RSV infection, and those infected had a high incidence of severe illness. In contrast, previous clinical trials evaluating live attenuated RSV showed no associated vaccine enhanced illness. We have used a mouse model to explore the immunopathogenesis of RSV infection. In this study cytokine mRNA expression was examined using 32P labeled oligonucleotide probes in Northern blot analyses of polyA RNA extracted from lungs of mice primed with various vaccine preparations then challenged nasally with live RSV. We have shown that upon challenge, priming of mice with inactivated virus or subunit F glycoprotein induced a pattern of cytokine mRNA expression suggesting a dominant Th2-like lymphocyte response (relative increase in IL-4 mRNA expression). In contrast, challenge of mice primed with live RSV by parenteral or mucosal routes induced a Th1-like pattern of cytokine mRNA expression (relative decrease in IL-4 mRNA expression compared to IFN-gamma mRNA expression). Thus, the formulation and route of delivery of vaccine products can influence the pattern of cytokine expression in lung upon RSV challenge. PMID- 8345195 TI - Selective tolerance to the E1 protein of rubella virus in congenital rubella syndrome. AB - Rubella virus (RV) infection of the fetus in the first trimester of pregnancy usually results in severe birth defects collectively termed Congenital Rubella Syndrome (CRS) and is frequently associated with prolonged RV persistence in the infant. Immunological tolerance to RV is believed to contribute to viral persistence, but the mechanism for this is unknown. In this study, RV-specific antibody responses in CRS patients and healthy controls who had experienced Rubella infection postnatally were compared to determine if there were differences that might account for RV persistence in the former group. Levels and functional affinities of IgG specific for individual RV proteins (E1, E2, and C) were measured by enzyme immunoassay (EIA). Relative amounts of RV protein specific IgG directed to linear and topographic epitopes were compared by immunoblots run under reducing or nonreducing conditions, respectively, and biological activity was determined by hemagglutination inhibition (HAI) assay. Results showed that both CRS patients and control subjects had comparably high levels of IgG directed to whole RV and to RV E2 and C proteins as measured by EIA. However, in contrast to the controls, CRS patients were found to have significantly reduced levels of antibodies directed to RV E1 protein and its linear (but not topographic) epitopes. Also, functional affinities of specific IgG directed to whole RV and E1 protein, as well as hemagglutination inhibition titers, were found to be significantly lower in CRS patients than in controls. The data suggest that intrauterine exposure to RV may result in selective immunological tolerance to the RV E1 protein. A model is presented that accommodates the serological findings of this investigation within a proposed mechanism of RV persistence resulting from selective immunological tolerance to RV E1 protein. PMID- 8345196 TI - Synergism between IFN-gamma and IL-1 alpha/beta in growth inhibition of an allografted tumor. AB - Soluble effector molecules involved in the rejection of allografted mouse Meth A (3-methylcholanthrene-induced ascites type tumor) cells were examined. A potent antiproliferative activity against the tumor cells was detected in the culture supernatant of leukocytes that had infiltrated into the peritoneal cavity of C57BL/6 mice on days 6-8 after transplantation, when the i.p. transplanted Meth A cells were undergoing rejection. Studies with neutralizing antibodies indicated that both IFN-gamma and IL-1 alpha/beta were required for the activity but that TNF-alpha was not. Actually, mouse rIFN-gamma and rIL-1 alpha/beta used, at the concentrations found in the culture supernatant determined by ELISA, were able to reconstitute the potent antiproliferative activity, although each cytokine alone had a weak growth inhibitory activity against Meth A cells. The half-maximal inhibition was observed with 0.02-0.03 U/ml of rIL-1 alpha/beta at 1-100 U/ml of rIFN-gamma. The synergistic growth inhibitory effect of these cytokines also was observed with four of 15 mouse transformed cell lines tested, indicating that the effect was not specific to Meth A cells. These findings suggest that IFN-gamma and IL-1 alpha/beta participate as soluble effector molecules in the rejection of some allografted tumor cells including Meth A cells. PMID- 8345197 TI - Quantitation and kinetics of blood monocyte migration to acute inflammatory reactions, and IL-1 alpha, tumor necrosis factor-alpha, and IFN-gamma. AB - Monocytes migrate from the blood into acute inflammatory reactions, where they differentiate into macrophages, and after 12 to 24 h become the predominant histologic feature of the inflammatory infiltrate. The quantitation of monocyte migration into these reactions has been difficult. This report employs a novel combination of techniques to isolate highly purified monocytes from the blood of rats, and shows that these cells have a normal t1/2 of 26 h and migrate efficiently after i.v. injection into cutaneous acute inflammatory sites. Monocytes labeled with 51Cr accumulated in delayed-type hypersensitivity reactions, and sites injected with killed Escherichia coli, LPS, poly-inosine: cytosine, zymosan-activated serum (ZAS), a source of C5adesArg, and the cytokines IL-1 alpha, TNF-alpha, and IFN-gamma. Both radiolabeled monocytes and neutrophils migrated rapidly to E. coli, LPS, ZAS, IL-1 alpha, and TNF-alpha with a large increase in cell accumulation by 2 h. Neutrophil migration declined rapidly to undetectable levels by 3 to 4 h to all five stimuli, and monocyte migration to ZAS and IL-1 alpha also declined by this time. In contrast, E. coli, LPS, and TNF alpha caused a sustained migration of monocytes for 5 to 6 h, long after neutrophils had stopped accumulating. Intradermal IFN-gamma did not recruit neutrophils but stimulated a prolonged monocyte migration from 1 to 6 h. Combinations of LPS, TNF-alpha, and IFN-gamma synergistically enhanced the late (> 5 h) but not the early phase of monocyte recruitment. In conclusion, purified monocytes isolated from rat blood can be used to quantify monocyte migration in vivo, and these cells migrate rapidly to cutaneous inflammation and in response to chemotactic factors, IL-1 alpha, TNF-alpha, and IFN-gamma, with initial kinetics similar to those of neutrophils. However, monocyte-selective mechanisms are induced by IFN-gamma and also appear to be involved in prolonged monocyte migration to TNF-alpha, LPS, and E. coli. PMID- 8345198 TI - Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin. AB - Altered macrophage function after thermal injury is associated with increased production of PGE2 and TNF. However, it is not clear why synthesis of both cellular products remains elevated, as PGE2 is a potent inhibitor of TNF secretion. We studied the relationship between PGE2 and TNF synthesis in a murine model of thermal injury, and examined the effect of prostaglandin blockade on splenic macrophage secretion of these mediators of inflammation. LPS-stimulated production of PGE2 was significantly elevated in burn groups compared with sham burned controls (pg/ml mean(SEM); sham 151(32): burn 597(147), p < 0.01). TNF production was similarly increased after thermal injury (pg/ml mean(SEM); sham 62(20): burn 928(316), p < 0.01). In vitro culture of macrophages with indomethacin augmented LPS stimulated TNF production in sham-burned controls but did not affect synthesis in burn groups, suggesting a loss of PGE2-dependent regulation of TNF synthesis after thermal injury. Direct measurement of TNF secretion as a function of exogenous PGE2 confirmed this dissociation between PGE2 and TNF synthesis, as burned animals displayed a 5-fold reduction in sensitivity to PGE2-induced inhibition of TNF, when compared with sham-burned controls (ID50 PGE2 molar; sham 1.26 x 10(-8): burn 6.43 x 10(-8), p < 0.05). In vivo pretreatment of burn groups with indomethacin for 5 days before assay partially restored sensitivity to the prostaglandin, and significantly down regulated synthesis of both TNF and PGE2. These data show that thermal injury is associated with a loss of PGE2-dependent down-regulation of TNF synthesis, which accounts at least in part for increased TNF in these animals. In vivo cyclooxygenase blockade partially restored sensitivity to the prostaglandin and consequently down-regulated synthesis of TNF. These data further support existing evidence that suggests a potential therapeutic role for cyclooxygenase blockade after major thermal injury and trauma. PMID- 8345199 TI - Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro. AB - Transforming growth factor-beta (TGF-beta) has been shown to be produced in the central nervous system (CNS). The functions of TGF-beta, however, remain to be elucidated. We investigated the effects of TGF-beta on the proliferation, activation, and cytokine production of isolated microglia in vitro. TGF-beta dose dependently suppressed the acid phosphatase activity of and formation of superoxide anion by LPS activated microglia. It also suppressed the IFN-gamma induced expression of class II MHC Ag- and the production of cytokines, IL-1, IL 6, and TNF-alpha, by these cells. TGF-beta also inhibited the proliferation of microglia that was induced by either GM-CSF or M-CSF. Because various immunoregulatory cytokines are produced in the CNS that serve as autocrine or paracrine mediators it is suggested that TGF-beta could be a negative regulator in the CNS cytokine network. It may play a role in the development of various disease processes in the CNS by inhibiting the function of microglia in inflammation or in immunoregulation. PMID- 8345200 TI - Clusterin, the human apolipoprotein and complement inhibitor, binds to complement C7, C8 beta, and the b domain of C9. AB - Clusterin is a heterodimeric multifunctional protein expressed in a variety of tissues and cells. It forms high density lipid complexes in plasma and participates in the control of the lytic activity of the late complement complex (TCC, C5b-9). Together with vitronectin, clusterin binds to the nascent amphiphilic C5b-9 complex, rendering it water soluble and lytically inactive. To define the interactions that underlie the complement-inhibitory function of clusterin, we have examined the binding interactions between [125I]clusterin and the isolated components of the complex, C5b-6, C7, C8, and C9 and vitronectin. By using ligand blotting in the presence of Tween, specific binding of the labeled clusterin with C7, the beta-subunit of C8 and C9 was detected. Binding to C9 was competed by polymerized C9, but not by C8, C7, C6, and CD59, suggesting that the conformational change occurring during the hydrophilic-amphiphilic transition of C9 exposes the interaction site for clusterin. When thrombin-treated C9 was analyzed, clusterin was found to recognize the C9b fragment containing the hydrophobic membrane interaction segment. Both subunits of clusterin interact with C9 and are similarly potent in inhibiting C5b-9-mediated hemolysis and Zn+(+)-induced C9 polymerization. These results show that clusterin exerts its inhibitory effect by interacting with a structural motif common to C7, C8 alpha, and C9b. PMID- 8345201 TI - Regulation of neutrophil-derived IL-8: the role of prostaglandin E2, dexamethasone, and IL-4. AB - Historically, the neutrophil has been perceived as a terminally differentiated leukocyte with limited ability to produce de novo proteins. Furthermore, in the context of acute inflammation the activated neutrophil has been appreciated only for its ability to release various proteases, reactive oxygen, and arachidonic acid metabolites. Recently, the neutrophil has been shown to have the capacity to produce a number of cytokines that may be instrumental in orchestrating the progression of acute inflammation to a more chronic and specific immune response. These cytokines include IFN-alpha, M-CSF, G-CSF, TNF, IL-1, and IL-6. Our laboratory and others have shown that neutrophils produce IL-8 in response to LPS or a phagocytic challenge. Although these studies have shown the induction of IL 8 from polymorphonuclear neutrophils (PMN), relatively little is known regarding the regulation of PMN-derived IL-8. Because PMN and monocytes share the same stem cell, and monocyte-derived IL-8 is regulated by prostaglandin E2 (PGE2), glucocorticoids (dexamethasone; DEX) and the T-Lymphocyte-derived IL-4, we postulated that PMN-derived IL-8 production may be regulated in a similar manner. To test this hypothesis, PMN were isolated (> 99% pure) from peripheral blood and cultured in media with 5% FCS in the presence or absence of LPS (10 ng/ml; a concentration of LPS that induced the half-maximal production of PMN-derived IL 8) and in the presence or absence of DEX (10(-6) M to 10(-10) M), PGE2 (10(-6) M to 10(-10) M), or IL-4 (100 ng/ml to 100 pg/ml). PMN-derived IL-8 was measured using a specific sandwich ELISA. DEX and IL-4 in the presence of LPS were found to inhibit PMN-derived IL-8 in both a dose- and time-dependent fashion. DEX and IL-4 in concentrations of 10(-6) M and 10 ng/ml resulted in maximal inhibition of LPS-induced PMN-derived IL-8, respectively. Moreover, both DEX and IL-4 administration could be delayed 4 hr post-stimulation with LPS and result in significant suppression of PMN-derived IL-8. Interestingly, in contrast to the regulation of monocyte-derived IL-8 by PGE2, PGE2 treatment of PMN failed to inhibit the generation of LPS-induced IL-8. Northern blot analysis of steady state IL-8 mRNA demonstrated that both DEX and IL-4 treatment of PMN resulted in a 40 and 52% reduction in LPS-stimulated PMN-derived IL-8 mRNA, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345202 TI - Recombinant tetravalent group A streptococcal M protein vaccine. AB - Previous studies have shown that the amino-terminal regions of group A streptococcal M proteins contain primarily protective (opsonic) epitopes and not tissue-cross-reactive epitopes. Limited primary structures from multiple serotypes of M protein containing only protective epitopes could potentially be linked together to form a broadly protective vaccine. The present studies were undertaken to determine the protective immunogenicity of a recombinant, multivalent hybrid molecule containing amino-terminal subunits of types 24, 5, 6, and 19 M proteins. Polymerase chain reaction primers were designed to amplify emm gene fragments ranging from 35 to 113 codons. The PCR products were ligated in tandem and inserted into pKK223-3. The tetravalent M protein that was purified from extracts of Escherichia coli migrated as a single band on SDS-PAGE with an apparent m.w. of 31 kDa. In immunoblot analyses, the hybrid protein reacted with serotype-specific antisera indicating that it contained all four M protein subunits. Rabbits immunized with the purified tetravalent M protein developed significant antibody levels against all four serotypes of native M proteins represented in the hybrid protein. None of the antisera cross-reacted with human tissues. The immune sera also opsonized all four serotypes of group A streptococci. Our data show that a hybrid protein containing subunits from multiple M proteins can evoke broadly protective immune responses without tissue cross-reactive antibodies. PMID- 8345203 TI - Molecular analysis of IgE H-chain transcripts expressed in vivo by peripheral blood lymphocytes from normal and atopic individuals. AB - The low levels of IgE produced by PBMC from normal individuals has so far prevented an analysis of their IgE H chain repertoire. Using a nested polymerase chain reaction approach, we were able to detect epsilon transcripts in all normal and allergic individuals we investigated. We further cloned epsilon CDR3/FW4 regions from two normal and two atopic individuals with low serum IgE levels. Sequence analysis of 104 clones identified 26 different epsilon CDR3/FW4 regions and an additional number of clonally related transcripts in the two atopic individuals. Preferential usage of DH genes from the DXP family (33%) and of the JH4b gene (35%) were observed, similar to reported findings for the IgM-producing peripheral blood B cell subset. Using CDR3 specific oligonucleotides, we detected the CDR3/FW4 regions of a particular set of clonally related epsilon transcripts in mu and gamma 4 transcripts of the same individual. This finding demonstrates the in vivo production of IgE together with the two other Ig isotypes (IgM and IgG4) by the progeny of a common B cell precursor, and suggests a possible mechanism for regulating the allergic response. The clonally related epsilon transcripts were found to be only of the secreted form. We give also evidence that the IgE-producing B cells undergo somatic mutation because a number of identical mutations were observed in the FW4 regions of epsilon and mu clonally related transcripts. Some of these mutations were shared with other transcripts from the same and other individuals, supporting the existence of sequence specific hot spots for the somatic hyper-mutation machinery in the JH gene segments. PMID- 8345204 TI - Induction of IFN-alpha by HIV-1 in monocyte-enriched PBMC requires gp120-CD4 interaction but not virus replication. AB - IFN-alpha is in plasma of HIV-1 infected patients during early and late-stage disease and may play a role in control of virus replication. The stimulus for IFN alpha production, the cells that produce this cytokine, and the effectiveness of this IFN-alpha response for control of virus infection are not yet defined. Culture fluids from freshly isolated PBMC of HIV-1 seronegative donors contained high levels of IFN-alpha after exposure to 100 to 1000 infectious HIV-1 particles per culture. Levels of IFN-alpha induced by HIV-1 were directly dependent on the number of monocytes in cell preparations: No IFN-alpha was detected from T cell enriched PBMC. In monocyte cultures, induction of IFN-alpha by HIV-1 was relatively specific: Levels of IL-1 beta, IL-6, IFN-gamma, and TNF-alpha remained at baseline. Capacity of HIV-1 virions to induce IFN-alpha was not dependent on virus replication. IFN-alpha was induced by (a) heat-inactivated HIV-1, (b) virions from 8E5 cells, a cell line that releases noninfectious HIV-1, (c) HIV-1 infected cells fixed in paraformaldehyde, and (d) T cell-tropic HIV-1 that binds to but does not infect monocytes. Capacity of HIV-1 virions and HIV-1 infected cells to induce IFN-alpha was completely inhibited by soluble rCD4 or mAb against CD4 or gp120. Antibodies against CD4, however, did not induce monocytes to produce IFN-alpha. HIV-1-induced IFN-alpha production was inhibited by antibodies against both V3 loop determinants and the CD4 binding site of gp120. Further, sera and purified immunoglobulin from HIV-1 infected patients also inhibited HIV 1-induced IFN-alpha production. These observations suggest that potentially protective antiviral responses associated with IFN-alpha production in HIV-1 infected patients are inhibited by the development of antibodies against gp120. PMID- 8345205 TI - Cord blood contains high numbers of autoimmune T cells recognizing multiple myelin proteins and acetylcholine receptor. AB - To analyze Ag-specific T cell autoimmunity in the newborn, umbilical cord blood cells of newborns were investigated by an immunospot assay for occurrence and numbers of cells secreting IFN-gamma after short-term culture in presence of myelin basic protein (MBP), proteolipid protein, myelin associated glycoprotein, nicotinic acetylcholine receptor and the synthetic MBP amino acid sequences 1-20, 63-88, and 110-128. These Ag were chosen because they represent putative targets for autoimmune attack in multiple sclerosis and myasthenia gravis. Surprisingly, numbers of T cells recognizing MBP, proteolipid protein, MBP peptides, and acetylcholine receptor were high in cord blood of newborns compared to peripheral blood of patients with neurologic diseases. No immunodominant T cell epitope could be discerned among the Ag included. The responses to purified protein derivate and PHA were lower among cord blood cells than peripheral blood cells of adults. Parallel enumeration of autoimmune T cells in cord blood and peripheral blood obtained from corresponding mothers at delivery, revealed that the high cell numbers in newborns were not a result of contamination from the mothers blood. The high numbers of T cells recognizing nervous system myelin proteins and acetylcholine receptor in cord blood could have importance for the mechanism and timing of tolerance induction, and also reflect excessive myelination and receptor maturation at birth. PMID- 8345206 TI - HIV-induced loss of CD44 expression in monocytic cell lines. AB - We have found that HIV-1 infection of monocytic cell lines results in a new adhesion phenotype. Whereas uninfected cells grow as single cell suspensions, HIV infected cells grow as large aggregates. When the expression of adhesion molecules was investigated, CD44 was almost completely depleted from the surface of HIV-infected cells. Immunoprecipitation with mAb confirmed the loss of CD44 from the surface of infected cells. In addition, loss of surface CD44 was not due to formation of internal complexes or release into the culture supernatant. Soluble CD44 was not detected in culture supernatant from HIV-infected cells. Northern blot analysis showed an altered RNA pattern in HIV-infected cells. The high molecular mass CD44 RNA (7.0 kb) was lost from infected cells, and the low molecular mass CD44 RNA (1.2 kb) remained. We have previously shown that anti CD44 mAb induces homotypic adhesion in CD44+ cell lines. In this report, we show that homotypic adhesion of the HIV-infected cells occurs through a different mechanism than anti-CD44 mAb-induced aggregation. The homotypic adhesion in infected cells was CD18-mediated, but anti-CD44 mAb-induced homotypic adhesion in uninfected cells was CD18-independent. The change in adhesion phenotype and the loss of CD44 from the surface of HIV-1-infected monocytic cells are discussed in terms of their potential implications in cell-to-cell transmission of HIV. PMID- 8345207 TI - Responses of mesangial cells of autoimmune mice to cytokines. AB - Glomerulonephritis is one of the most important complications of SLE. The genesis of the renal lesions in this disorder is determined by a cascade of events that leads to mesangial cell proliferation as one of the hallmarks of the kidney disease. The current study examines the postulate that there may be intrinsic abnormalities in the mesangial cells of the autoimmune host which predisposes it to develop nephritis. It investigates the possibility that growth responses of mesangial cells of the autoimmune MRL/MpJ-lpr/lpr mice are different from those of their congenic normal MRL/MpJ-(+)/+ (MRL-(++)) counterparts when cultured with various cytokines. To test this possibility, growth responses of mesangial cells as assessed by [3H]TdR uptake were measured when these cells were cultured with epidermal growth factor, platelet-derived growth factor, transforming growth factor-beta, and 1,25-dihydroxy vitamin D3. Epidermal growth factor stimulated the growth of mesangial cells of both strains of mice equally, but platelet derived growth factor appeared to elicit a more pronounced proliferative response from mesangial cells of the autoimmune mice. In regard to inhibitory substances tested, mesangial cells of autoimmune MRL-lpr mice appeared to be relatively insensitive to the suppressive effects of transforming growth factor-beta and 1,25-dihydroxy vitamin D3. Collectively, the response profile of mesangial cells of the MRL-lpr mice suggests that these cells have a tendency to proliferate when they are acted on by cytokines, so that they may be more susceptible to develop the proliferative lesions seen in the nephritis of SLE. PMID- 8345208 TI - Concurrent infection of human macrophages with HIV-1 and Mycobacterium avium results in decreased cell viability, increased M. avium multiplication and altered cytokine production. AB - The effects of a concurrent HIV-1 and Mycobacterium avium infection in vitro were assessed in human peripheral blood-derived macrophages (M phi). M phi were infected with HIV-1Ba-L strain for 14 days then infected with M. avium (HIV/M. avium) or treated with LPS (HIV/LPS). At various times after M. avium or LPS treatment, Mo phi cultures were harvested for quantitation of HIV and M. avium replication, as well as M phi cellular viability. In addition, mRNA and supernatants were collected for assessment of induction of the cytokines TNF alpha, IL-1 beta and IL-6. M. avium multiplication was greater in HIV-infected M phi, whereas no difference in virus production, based on p24 and RT values, was observed between HIV-infected cells and HIV/M. avium or HIV/LPS M phi. M. avium infection of HIV-1-infected M phi also caused a decrease in viability of the M phi. HIV-1/M. avium-infected M phi had a 24 h delay in induction of TNF-alpha steady state mRNA when compared with HIV/LPS or M. avium only or LPS-only treated M phi. HIV infection also increased the amount and the length of induction of IL 1 beta and IL-6 steady state mRNA stimulated by either M. avium or LPS. In addition, prolonged and increased protein production of TNF-alpha, IL-6, and IL-1 beta was observed in HIV/M. avium-infected cells when compared with the other treatments. In direct contrast to M. avium infection, no significant differences in LPS-induced protein production of the three cytokines was observed between HIV 1-infected and -noninfected M phi. Treatment of HIV/M. avium-infected cells with human rGM-CSF did not increase either the time or quantity of induction of TNF alpha mRNA or protein production in HIV/M. avium-infected M phi. The increase in M. avium numbers, dysregulation of cytokine production, and subsequent cell death seen in vitro in HIV/M. avium-infected human M phi may reflect part of the underlying cause of the highly disseminated M. avium disease pattern observed in AIDS patients. PMID- 8345209 TI - Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees. AB - Costimulation of neutrophils and cytokines may play an important role in organ injury in sepsis. Pentoxifylline inhibits various neutrophil functions in vitro, and attenuates endotoxin-induced production of TNF in both in vitro and in vivo models. To assess the effect of pentoxifylline on neutrophil activation in endotoxemia, nine adult chimpanzees (Pan troglodytes) were i.v. injected with saline (n = 2), Escherichia coli endotoxin (4 ng/kg; n = 4), or E. coli endotoxin (4 ng/kg) in combination with pentoxifylline (500 mg/3 h, starting 30 min before the endotoxin injection; n = 3). Serial blood samples were obtained for measurements of leukocyte counts and the granulocytic proteinases elastase complexed with alpha 1-antitrypsin and lactoferrin, and cytokines during the next 5 h. No changes were observed in the saline-treated chimpanzees. Endotoxin induced a marked leukocytosis and neutrophilia, which were slightly reduced by pentoxifylline. In contrast, pentoxifylline almost completely prevented endotoxin induced neutrophil degranulation: peak elastase-alpha 1-antitrypsin was 164 +/- 21 ng/ml (mean +/- SE) after endotoxin alone, vs 71 +/- 7 ng/ml after endotoxin with pentoxifylline (t = 3 h; p < 0.05); peak lactoferrin was 329 +/- 15 and 182 +/- 5 ng/ml, respectively (t = 5 h; p < 0.05). Pentoxifylline also inhibited the endotoxin-induced release of TNF (271 +/- 26 vs 55 +/- 23 pg/ml at t = 1.5 h; p < 0.05) and IL-6 (225 +/- 42 vs 73 +/- 25 pg/ml at t = 2 h; p < 0.05). IL-8 release was not significantly inhibited by pentoxifylline. In none of the animals activation of the C system could be detected. We conclude that pentoxifylline attenuates neutrophil activation in endotoxemia in chimpanzees, probably in part by inhibiting the release of TNF. PMID- 8345210 TI - Cell death by apoptosis in epidermal biology. AB - Homeostasis in continually renewing tissues is maintained by a tightly regulated balance between cell proliferation, cell differentiation, and cell death. Until recently, proliferation was thought to be the primary point of control in the regulation of normal tissue kinetic homeostasis and as such has been the major focus of both understanding the etiology of disease and developing therapeutic strategies. Now, physiologic cell death, known as apoptosis (a-pop-to' sis, a-po to' sis [Thomas CL (ed.): Taber's Cyclopedic Medical Dictionary. F.A. Davis, Co., Philadelphia, 1989)] has gained scientific recognition as an active regulatory mechanism, complementary, but functionally opposite, to proliferation with important roles in shaping and maintaining tissue size and prevention of disease. In this review we will describe the concept of apoptosis and discuss possible molecular mechanisms of its regulation that may have implications for skin biology. PMID- 8345211 TI - Hemopoietic stem cell inhibitor (SCI/MIP-1 alpha) also inhibits clonogenic epidermal keratinocyte proliferation. AB - The maintenance and regulation of continuously renewing tissues is ultimately controlled at the level of stem-cell proliferation. We have recently identified a reversible inhibitor of hemopoietic stem-cell proliferation (stem-cell inhibitor [SCI]), which is identical to the macrophage inflammatory protein, MIP-1 alpha, a 69-amino-acid heparin-binding cytokine. To test the cell/tissue specificity of the inhibition of proliferation by SCI/MIP-1 alpha, we have investigated its activity on epidermal keratinocytes, the principal cell type of another continuously renewing tissue. Here we show that SCI/MIP-1 alpha inhibits the proliferation of epidermal keratinocytes in vitro and that the MIP-1 alpha mRNA is present in epidermal Langerhans cells but not in keratinocytes. This suggests an important growth regulatory function for SCI/MIP-1 alpha in keratopoiesis, as well as hemopoiesis, and may also indicate a novel role for the epidermal Langerhans cell. As SCI/MIP-1 alpha can inhibit the proliferation of embryologically distinct precursor cells, this raises the possibility that it may also function in a number of other tissues. PMID- 8345212 TI - MCP-1 mRNA expression in basal keratinocytes of psoriatic lesions. AB - In addition to hyperproliferation of keratinocytes, psoriasis is characterized by pronounced leukocytic infiltration. In contrast to the epidermal localization of neutrophils and T lymphocytes, macrophages are almost exclusively restricted to the dermal compartment. By immunohistologic analysis, these dermal macrophages were mainly encountered in the papillary dermis and arranged along the rete ridges in close proximity to proliferating keratinocytes. Monocyte chemoattractant protein (MCP-1) anti-sense RNA probes yielded abundant signals over the proliferating basal keratinocytes of the tips of the rete ridges, and, to a lesser extent, in cells in the papillae. Thus, the strongest MCP-1 message in psoriatic lesions is found above the dermal-epidermal junction and this may explain the characteristic sub-basal distribution of dermal macrophages. These results suggest that MCP-1 is important in regulating the interaction between proliferating keratinocytes and dermal macrophages in psoriasis pathogenesis. PMID- 8345213 TI - Studies of contact hypersensitivity induction in mice with optimal sensitizing doses of hapten. AB - To avoid unsuspected and unwanted consequences of excess hapten during epicutaneous sensitization, optimal sensitizing doses of dinitrofluorobenzene (DNFB) were determined for several ultraviolet B radiation (UVB)-resistant and UVB-susceptible strains of mice. Using these doses of hapten applied epicutaneously or injected intracutaneously into normal or UVB-exposed body wall skin, it was determined that four consecutive daily exposures to UVB prevented contact hypersensitivity induction in all mice when optimal sensitizing doses of DNFB were applied epicutaneously. By contrast, UVB-resistant, but not UVB susceptible, mice developed contact hypersensitivity when an optimal sensitizing dose of DNFB was injected intracutaneously into UVB-irradiated skin. Moreover, whereas UVB-susceptible mice failed to develop contact hypersensitivity when an optimal sensitizing dose of DNFB was painted on skin exposed to a single dose of UVB, UVB-resistant mice did develop contact hypersensitivity under similar circumstances. Based on these results, it is concluded that 1) conventional doses of epicutaneously applied haptens induce contact hypersensitivity with the aid of antigen-presenting cells derived from both the epidermis and the dermis, 2) the phenomenon of UVB susceptibility is mediated by cells and molecules within the dermis when conventional doses of hapten and UVB radiation are employed, and 3) UVB susceptibility is mediated by cells and molecules within the epidermis when optimal sensitizing doses of hapten and a single exposure to UVB are employed. PMID- 8345214 TI - Identification of a mammalian melanosomal matrix glycoprotein. AB - Antiserum raised in rabbits against the Triton X-100 insoluble fraction of melanosomes from mouse melanoma cells specifically decorates the internal matrix of melanosomes in immunoelectron microscopy. In metabolic labeling studies, the antiserum recognizes a protein of 94 kDa, which is processed to a band of 53 kDa. Whereas the precursor is relatively soluble in buffers containing Triton X-100, the processed protein requires the addition of sodium dodecyl sulfate for effective solubilization, as would be expected for a melanosomal matrix constituent. Tunicamycin reduces the Mr of the nascent protein to 75 kDa, but deoxymannojirimycin and swainsonine have no effect, suggesting that following initial glycosylation in the endoplasmic reticulum, the protein is not subject to processing by glycosidases in the Golgi apparatus or may bypass it entirely. Subcellular fractionation followed by immunoblotting confirms that the protein is present in the melanosome-rich, large granule fraction. Expression of the protein is regulated differently from that of the tyrosinase-related protein family. Conditions that greatly stimulate expression of tyrosinase-related proteins do not affect matrix protein expression, nor is the protein immunologically related to the tyrosinase-related protein family. Our results suggest that we have identified an authentic component of the mammalian melanosomal matrix, and that its characteristics lend support to a bipartite pathway for melanosomal biogenesis. PMID- 8345215 TI - Combination of 4-hydroxyanisole and all-trans retinoic acid produces synergistic skin depigmentation in swine. AB - A combination of 4-hydroxyanisole (4HA) and all-trans retinoic acid (TRA) was found to synergistically cause moderate to complete depigmentation of Yucatan swine skin. Two hyperpigmentation models were used: Natural dark-skinned swine, a potential model for melasma-like disorders, and ultraviolet light-stimulated hyperpigmentation, a model of solar lentigines. Test materials were applied twice daily, 5 d/week, to dorsal flank skin. Application sites were graded at weekly intervals for skin color using a 0 to 4 grading scale. After 8 weeks of treatment of naturally dark swine skin, a combination of 2% 4HA and 0.01% TRA produced grade 2 hypopigmentation (definite but moderate hypopigmentation). In contrast, 2% 4HA alone or 0.01% TRA alone did not produce significant hypopigmentation. After cessation of treatment, the 4HA/TRA-treated sites reverted to normal color within 7-12 weeks. The 4HA/TRA combination completely reversed the hyperpigmentation induced by ultraviolet light after 8 weeks of treatment. In vitro skin-penetration studies using hairless mouse and human skin show that skin penetration of 4HA was not significantly affected by adding 0.01% TRA. These data suggest that the observed synergy is not due to enhanced bioavailability of 4HA. We have demonstrated that combining low concentrations of 4HA and TRA results in effective skin lightening without causing irreversible depigmentation and with minimal local skin irritation. PMID- 8345216 TI - Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells. AB - The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses. PMID- 8345217 TI - Effect of phototherapy and urocanic acid isomers on natural killer cell function. AB - Ultraviolet (UV) radiation suppresses a variety of immune responses but it is uncertain whether this action contributes to the effectiveness of phototherapy. Urocanic acid (UCA) has been proposed as a mediator of the immunologic effects of UV. On exposure the naturally occurring trans-isomer of UCA in the skin changes into the cis-isomer, which has been demonstrated to mimic many of the immunomodulatory effects of UV irradiation. Natural killer (NK) cells play an important role in several immunologic processes and published evidence indicates that their activity is altered by UV irradiation. To ascertain the effect on NK cells of phototherapy used in the treatment of psoriasis, modulation of NK activity in psoriatic patients undergoing broad-band UVB, narrow-band UVB, or psoralen plus (PUVA) regimens was examined. This was compared with NK cell activity in psoriatic patients treated with topical coal tar and in normal subjects receiving broad band UVB. The NK cell activity of psoriatic and normal subjects was the same over a wide range of effector to target cell ratios. Almost all patients undergoing phototherapy exhibited depressed NK cell activity during or after irradiation, although the timing of the depression varied between the lamps used and may be related to dose. However, patients treated with topical coal tar showed unchanged NK cell activity throughout the therapy. The effect of UCA isomers on NK cell activity in vitro was also determined. It was found that cis-UCA induced a dose-dependent suppression of NK cell activity in both patients and normal subjects, whereas trans-UCA had hardly any effect in either group. Thus it is possible that there may be a correlation between cis-UCA formation in the epidermis and the modulation of NK cell activity that occurs during phototherapy. PMID- 8345218 TI - Lipid supplemented medium induces lamellar bodies and precursors of barrier lipids in cultured analogues of human skin. AB - Barrier function of cultured skin substitutes (CSS) is required for their effective use in clinical treatment of skin wounds, and for percutaneous absorption in vitro. Arachidonic, palmitic, oleic, and linoleic free fatty acids, in conjunction with the antioxidant alpha-tocopherol acetate (lipid supplements, "LS"), were added to nutrient media of CSS to provide precursors of epidermal barrier lipids. CSS were composed of human keratinocytes (HK), fibroblasts (HF), and collagen-glycosaminoglycan substrates, and were incubated for 14 d submerged or lifted to the air-liquid interface in media based on MCDB 153 +/- LS. Duplicate samples (30 cm2) were harvested and the epidermal analogue was analyzed for total protein, total DNA, total lipid, lipid fractions including acylglucosylceramide (AGC), and presence of lamellar bodies. Significant increases (p < 0.05) were detected between CSS incubated in +LS medium for total lipid, total DNA, ceramide, glucosylceramide, triglycerides, and diglycerides. AGC and lamellar bodies were detected only in epithelia of CSS incubated in +LS medium. These data show that free fatty acids, vitamin E, and lifting of CSS promote increased epithelial morphogenesis compared to CSS cultured submerged without lipid supplements. Presence of lamellar bodies and AGC suggests enhanced production in vitro of barrier-associated epidermal lipids. PMID- 8345219 TI - Inhibition of cholesterol and sphingolipid synthesis causes paradoxical effects on permeability barrier homeostasis. AB - Cholesterol, fatty acid, and sphingolipid synthesis are required for barrier homeostasis, as demonstrated by studies where synthesis of these species is stimulated in parallel with barrier repair. Moreover, blockade of synthesis of these lipids with inhibitors of two of the rate-limiting enzymes, HMGCoA reductase (lovastatin, fluvastatin) and serine palmitoyl transferase (beta chloroalanine), alters the kinetics of barrier repair. Whereas these studies demonstrated a requirement for these lipids individually, we asked here whether these lipids are required in either an additive or cooperative fashion. We applied each class of inhibitor alone or the two classes of inhibitors together to acetone-treated skin, or each class separately to essential fatty acid deficient murine skin. When fluvastatin or beta-chloroalanine was applied individually to acetone-treated skin, each caused a delay in the early or late stages of barrier recovery, respectively (assessed as transepidermal water loss). However, when applied together they caused no further worsening at the early time point and a paradoxical improvement at the later time points. This improvement correlated with an accelerated return of sphingolipids, which was perhaps due to a global stimulation of lipid synthesis induced by HMGCoA reductase inhibitors. In essential fatty acid deficient animals, inhibition of HMGCoA reductase caused drastic worsening of both clinical appearance and barrier function, but beta chloroalanine caused a paradoxical improvement, which correlated with a significant reduction in epidermal sphingolipids. These results are consistent with a requirement for both cholesterol and sphingolipids for barrier homeostasis, and also with the suggestion that both of these lipids must be present (with free fatty acids) for optimal barrier function. PMID- 8345221 TI - Cold shock induces the synthesis of stress proteins in human keratinocytes. AB - Heat shock proteins or stress proteins are synthesized when cells are exposed to a wide variety of physiologic stresses. The stress response is evolutionarily highly conserved, suggestive of an essential function(s) for the survival of organisms, protecting them from harmful trauma. Exposure to cold induces a stress response in organisms such as Drosophila melanogaster and Sarcophaga crassipalpis and this led us to determine whether or not cold shock responses occur in human skin after exposure to cold such as might occur during cryopreservation of tissues or cryosurgery. Biopsies taken from fresh human skin at chest surgery were exposed to 4, 15, 20, and 37 degrees C (control) for 60 min and then allowed to incorporate 35S-methionine at 37 degrees C for up to 3 h. Proteins from the epidermis were extracted and analyzed by sodium dodecyl-sulfate-polyacrylamide gel electrophoresis. At 15 degrees C and below there was increased synthesis of 90 and 72 kD proteins 2 h after shocking. The 72-kD protein was identified as a heat shock protein using a monoclonal antibody to HSP72 and it is proposed from electrophoretic evidence that the 90-kD protein is also a heat shock protein. Clearly, cold shock stimulates a stress response in human epidermis altering the spectrum of proteins expressed and inducing the synthesis of heat shock proteins. PMID- 8345220 TI - Relationship between heat shock protein induction and the binding of antibodies to the extractable nuclear antigens on cultured human keratinocytes. AB - The importance of environmental factors such as ultraviolet light and temperature in the pathogenesis of cutaneous lupus erythematosus is well recognized. Recent evidence suggests the presence of autoantibodies to heat shock proteins (HSP) in the sera and enhanced expression of the HSP70 gene in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. We designed experiments to determine how HSP or stress protein inducers affect the cell surface binding of IgG antibodies from sera containing anti-SS-A/Ro and anti ribonuclear protein (RNP) antibodies to keratinocytes because these antibodies are considered to be one of the immunologic triggers of cutaneous lupus erythematosus. Immunofluorescence and immunoblot analysis using a monoclonal antibody to the 72 kDa of HSP revealed that an 18-h incubation with 10 micrograms/ml of delta 12-PGJ2, one of cytotoxic prostaglandins, induced HSP72 formation in cultured human keratinocytes. delta 12-PGJ2 augmented the binding of IgG antibodies from sera containing anti-U1RNP and anti-SS-A/Ro antibodies to cultured keratinocytes, but produced no enhancement of the binding of IgG antibodies from sera containing anti-Sm or anti-DNA antibodies. Similar results were also obtained by using flow cytometry analysis. HSP was also induced by ultraviolet B irradiation. These results suggest that exposure of keratinocytes to stressors such as delta 12-PGJ2 and ultraviolet light increases the binding sites for U1RNP,SS-A/Ro, and SS-B/La antibodies. The association between HSP induction and the appearance of extractable nuclear antigens may provide a better understanding of why environmental stimuli can promote the development of erythematous lesions in the skin. PMID- 8345222 TI - Demonstration of 72-kDa and 92-kDa forms of type IV collagenase in human skin: variable expression in various blistering diseases, induction during re epithelialization, and decrease by topical glucocorticoids. AB - Type IV collagenases have been shown to play an important role in tumor metastasis and wound healing. In the present study, we have demonstrated the presence of 72-kDa and 92-kDa forms of type IV collagenase in human skin by biochemical and in situ hybridization techniques. In situ hybridization allowed us to localize the 72-kDa form mostly to fibroblasts and the 92-kDa form to the epidermis and endothelial cells. The presence of type IV collagenase was confirmed by Western blotting. Enzyme activity was assayed in spontaneous blisters (18 subjects) and suction-induced blisters (29 subjects) by the zymography method, and by using type IV collagen as the substrate. Thus, it was possible to detect both the 92-kDa and 72-kDa forms in spontaneous and induced blisters. An especially high level of the 92-kDa enzyme was found in a bullous pemphigoid patient. Type IV collagenases were studied during re-epithelialization of the blister, using the suction-blister model. There was a marked induction of the 92-kDa type that was confirmed to be in the regenerating, migratory, epithelium by in situ hybridization studies. These results indicate that 92-kDa type IV collagenase may play an essential role in the normal physiology and integrity of the skin and may be an important regulator of re-epithelialization. It was also shown that potent topical glucocorticoid down-regulated the 92-kDa type collagenase, suggesting that glucocorticoids may have a beneficial role in some skin diseases by decreasing type IV collagenase activity and, thus, reducing tissue destruction. PMID- 8345223 TI - Microcirculatory functions in systemic sclerosis: additional parameters for therapeutic concepts? AB - To study the functional reactivity of the cutaneous microcirculation in progressive systemic sclerosis (PSS), hyperemic responses after arterial occlusion (3 min) and during local heating (42 degrees C) were investigated with simultaneous measurements of red blood cell flux and cutaneous oxygen tension (pcuO2) of the skin in female patients (n = 19) with PSS and in healthy female controls (n = 15). Additionally, serum levels of 6-keto-prostaglandin 1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, were compared to the microcirculatory data, and both were used to evaluate further a standardized therapy with 10-d intravenous calcitonin (100 IU/d) infusion in six PSS patients. In PSS, the initial mean pcuO2 value was significantly reduced and was inversely proportional to flux and to PGF1 alpha levels, whereas the flux and pcuO2 responses to the above hyperemic stimuli showed significant reductions, revealing a pattern of "hyperemic hypoxia" probably due to exhausted functional reserves of cutaneous perfusion. During calcitonin infusion significant rises in pcuO2 and temporarily in PGF1 alpha and flux were found. After 10 d of therapy, increased pcuO2 was associated significantly with decreased flux, indicating a shifting of blood from deeper regulatory vessels to the subepidermal capillaries. Both clinical improvement and the results of microcirculatory measurements demonstrate a beneficial effect of calcitonin on the cutaneous microcirculation in PSS patients, possibly due in part to a short-term increase in release of endogenous prostacyclin from the vascular endothelium during the infusion. The disturbed reactivity of the dermal vessels in PSS is important for the evaluation of therapeutic concepts and stresses, together with the elevated PGF1 alpha plasma levels, vascular factors in the pathogenesis of PSS. PMID- 8345224 TI - Impaired regulation of collagen pro-alpha 1(I) mRNA and change in pattern of collagen-binding integrins on scleroderma fibroblasts. AB - We explored the hypothesis that dermal fibroblasts isolated from patients suffering from systemic sclerosis are disturbed in their ability to interact functionally with native collagen fibers. Additionally, we investigated the expression of one collagen-binding integrin matrix receptor, alpha 1 beta 1 on those cells. Two populations of primary dermal fibroblasts were established, one from patients with systemic sclerosis and one from normal subjects. When cultured for 24 h in free-floating collagen gels, both types of fibroblasts down-regulated the cellular content of collagen pro-alpha 1(I) messenger ribonucleic acid, the systemic sclerosis fibroblasts less markedly than the normals. In normal, but not in systemic sclerosis fibroblasts, the kinetics of collagen gel contraction were directly proportional to the extent of the down-regulation. Fetal bovine serum stimulated collagen gel contraction in both populations. When grown in collagen gels in the presence of fetal bovine serum, no difference between systemic sclerosis and normal fibroblasts in capacity to down-regulate pro-alpha 1(I) was observed. Collagen-binding beta 1 integrins mediate the functional interactions between fibroblasts and the collagen fibers. To assess the cell surface expression of collagen-binding beta 1 integrins on fibroblasts, we labeled cells with 125I and subjected Triton X-100 extracts from them to immunoprecipitation with anti-beta 1 integrin immunoglobulin G. Among the systemic sclerosis fibroblasts, a larger number of isolates expressed low amount of alpha 1 beta 1 than did the fibroblasts isolated from normal individuals. Our data are compatible with the hypothesis that systemic sclerosis fibroblasts have a disturbed interaction with collagen fibers; this disturbance may in part be the result of an aberrant expression of collagen-binding beta 1 integrins. PMID- 8345226 TI - Effects of all-trans retinoic acid on glycosaminoglycan synthesis in photodamaged hairless mouse skin. AB - All-trans retinoic acid (tRA) was previously shown to be active in wrinkle reduction in the hairless mouse photoaging model. To address the questions of whether tRA also alters glycosaminoglycan (GAG) synthesis and whether observed wrinkle effacement can be attributed to changes in total GAG production, the effects of tRA on de novo GAG synthesis were examined in this model. Sulfated glycosaminoglycans (S-GAG) and the non-sulfated hyaluronic acid (HA) labeled with [3H]-glucosamine or [35S]-sulfate were found to diffuse differentially into the medium during the labeling period in the control animals (9% and 35% of total incorporated label for HA and S-GAG, respectively). Furthermore, the diffusion of HA into media was significantly changed after tRA treatment (from 9% to 24%), but no alteration was observed in the diffusion of S-GAG. Separation of epidermis and dermis indicated that the additional HA in medium after retinoid treatment primarily originated from the dermis. When incorporated label from the medium and skin fractions was combined, both labeling protocols revealed that 10 weeks of tRA treatment did not increase the total (medium plus skin) de novo synthesis of either HA or S-GAG. Wrinkle effacement as induced by retinoids in the photodamaged mouse skin therefore can not be related to an increased total GAG synthesis. PMID- 8345225 TI - Intracytoplasmic retention of type VII collagen and dominant dystrophic epidermolysis bullosa: reversal of defect following cessation of or marked improvement in disease activity. AB - It has been recently shown that the presence of perinuclear "stellate bodies" within the epidermis in patients with a form of dominant dystrophic epidermolysis bullosa named "transient bullous dermolysis of the newborn" corresponds to collections of type VII collagen. To determine the temporal relationship of this unique immunohistochemical defect with course of clinical disease activity, we have longitudinally studied the expression of two epitopes of type VII collagen (LH 7:2; L3d) in nine patients in four such kindreds by immunofluorescence and immunoelectron microscopic technique. In every infant so studied at the time of active blistering, type VII collagen was detectable primarily within basilar and, to a lesser extent, suprabasilar keratinocytes. In contrast, type VII collagen was detectable solely in linear array along the dermoepidermal junction in skin from each patient following complete cessation or at least marked diminution of visible clinical disease activity. These findings support the hypothesis that the temporary mechanical fragility and blistering of the skin in infants with this rare subset of dominant dystrophic epidermolysis bullosa reflect the presence of reduced amounts of type VII collagen along the dermoepidermal junction, and that this diminution may be the result of either a delay in transport and integration of type VII collagen from basilar keratinocytes into the skin basement membrane or excessive phagocytosis of type VII collagen. PMID- 8345227 TI - Cloning of the 5' mRNA for the 230-kD bullous pemphigoid antigen by rapid amplification of cDNA ends. AB - The 230-kD bullous pemphigoid antigen (BPAG1), defined by autoantibodies in patient sera, is a hemidesmosomal plaque protein in the same gene family as the intracellular proteins desmoplakin I/II and plectin. We had previously isolated, from a lambda gt11 library, overlapping cDNA clones with 6921 bp of mRNA sequence for BPAG1. The coding sequence encoded by these clones included the 3' stop codon but not the 5' coding and non-coding region of the mRNA. To obtain these sequences we used the polymerase chain reaction (PCR) method called rapid amplification of cDNA ends (RACE). The PCR products were cloned into plasmids and sequenced. With five PCR primers we were able to obtain overlapping clones containing the 5' region of the mRNA. An upstream stop codon in frame with the rest of the coding sequence demonstrates that the full 5' coding sequence is obtained. Four different PCR products from two separate reactions had the same 5' end, suggesting that this 5' end is near, or at, the transcription start site. No alternatively spliced clones were found and no transmembrane site was predicted, confirming that BPAG1 is an intracellular hemidesmosomal plaque protein. PMID- 8345228 TI - Persistent misconceptions in leprosy research. PMID- 8345229 TI - Bioavailability of dapsone on oral administration of Dapsomine--a comparative evaluation. AB - This study describes a comparative evaluation of dapsone kinetics in humans on administration of Dapsomine, a capsule containing dapsone 100 mg dispersed in oily-base suspension of clofazimine 50 mg. Seven untreated lepromatous leprosy patients were given one capsule of Dapsomine a day for seven days and the pharmacokinetics parameters in this group were compared with those from another group of seven patients who received dapsone 100 mg and clofazimine 50 mg separately. There were no statistically significant differences in parameters such as peak dapsone plasma concentration (Cmax), basal plasma level (C24h), time to peak level (tmax), absorption half-life (t1/2 alpha), elimination half-life t1/2 beta) and areas under plasma concentration-time curves (AUC0-8h) and AUC0 24h) between the two groups. PMID- 8345230 TI - Observations on attempted leprosy cultures in two media. AB - Suspensions of skin tissue material collected from lepromatous leprosy patients and material from mouse foot-pad harvests were inoculated into two media, viz., a biphasic medium and a minimal basal medium. The cultures were incubated at 37 degrees C and 15 degrees C. Small oval (or round) cells appeared in these cultures around the tenth day along with a few cystic structures; and they increased in number later, reaching the maximum around six-seven weeks. The above cells appeared acid-fast in some cultures and some of them appeared to split into pairs of acid-fast bacilli. The cells were most often seen in the biphasic medium at 37 degrees C. The identity of these structures is not known at this stage. PMID- 8345231 TI - Comparative study of short term results in two multidrug regimens in multibacillary leprosy. AB - Thirty lepromatous and Borderline lepromatous leprosy patients were treated with multidrug therapy in an open trial. Fifteen of them received the standard WHO multidrug regimen ie., rifampicin 600 mg and clofazimine 300 mg monthly, supervised, and dapsone 100 mg daily and clofazimine 100 mg on alternate days as self administered; the other 15 received a modified multidrug therapy regimen comprising of rifampicin 600 mg, clofazimine 100 mg and dapsone 100 mg daily for 21 days as suggested by the Indian Association of Leprologists, followed by the standard WHO regimen. The observation period was six months. Clinical, bacteriological, histological and immunological parameters were studied. The fall in morphological index was much faster in patients receiving modified multidrug therapy regimen compared to those receiving the standard WHO regimen. Otherwise, there was no difference between the two groups of patients. Five patients developed type I (upgrading) reaction with one developing ulnar nerve paralysis. No untoward effects of drugs were noted in the study subjects except for darkening of skin colour of all the patients. PMID- 8345232 TI - Electro neuro physiological studies in early tuberculoid leprosy. AB - Electro physiological studies were carried out in early tuberculoid type of leprosy in order to study their utility in detecting nerve damage before the onset of obvious functional deficit. Fifty-three cases showing one mixed nerve thickening in one limb were selected. Nerve conduction studies (both motor and sensory) were done using single blind technique. There was no statistically significant difference between the findings obtained from clinically thickened and non-thickened nerves. There was also no direct relationship between clinical sensory deficit and electro physiological abnormality. Clinical motor power loss was well correlated with electro physiological abnormalities. PMID- 8345233 TI - Adenosine deaminase activity in leprosy. AB - Serum adenosine deaminase (ADA) was studied in 60 patients of different types of leprosy and 50 healthy control subjects. ADA levels in patients with tuberculoid (50.50 +/- 5.22 U/L), borderline (41.14 +/- 3.89 U/L) and lepromatous leprosy (30.10 +/- .03 U/L) were higher than that in controls (17.84 +/- 2.78 U/L), thus correlating with the immunological status of patients. Patients with lepra reaction showed decreased ADA levels and higher grade of lepromin test positivity was associated with increased ADA activity. PMID- 8345234 TI - Application of filter paper method for collection of blood for MLPA test. AB - The results of MLPA test using serum and filter paper eluate have been compared in this paper. Testing 64 patient samples at 1:32 dilution, 31 were negative by both serum and eluate, 20 were positive by both, six were positive only by serum and one was positive only eluate. In six other cases eluate gave equivocal results while serum result was clearly positive. Some eluates negative at 1:32 dilution gave weak positive agglutination at 1:16 dilution. PMID- 8345235 TI - Evolving consensus on the probable nocardioform morphology of the leprosy bacillus. PMID- 8345236 TI - "Flu" syndrome associated with other systemic manifestations with once a month rifampicin in the treatment of multibacillary leprosy. PMID- 8345237 TI - Shoreline nails following type II lepra reaction. PMID- 8345238 TI - Mycetomas in leprosy. PMID- 8345239 TI - Solitary neurofibroma mimicking nerve abscess of leprosy. PMID- 8345240 TI - Reaction in borderline tuberculoid leprosy presenting with multiple subcutaneous nodules. PMID- 8345241 TI - Prevalence rate of leprosy. PMID- 8345242 TI - Disability grading systems in leprosy. PMID- 8345243 TI - [Dentin bonding: personal view and it's materialization]. PMID- 8345244 TI - [Review and outlook on sports dentistry]. PMID- 8345245 TI - [Production of monoclonal antibody that recognizes glycogen and its application for immunohistochemistry]. AB - In this study, I made a monoclonal antibody, using the mandibular condylar cartilage as antigen. By light microscopic immunocytochemical observations, this antibody reacted with the chondrocytes both in the mandibular condyle and the costal cartilage, hepatocytes and skeletal muscle cells. By electron microscopic immunocytochemical observations, reaction products (gold particles) were seen on the glycogen particles in the chondrocytes. Further, by dot blotting assay, this antibody was found to react directly with the purified glycogen. Meanwhile, all these reactions disappeared after alpha-amylase digestion. These results indicate that this antibody specifically recognizes glycogen or glycogen-related sugar chains. Therefore, I think that this antibody is very much useful for detecting the glycogen instead of the PAS reaction, since PAS reaction is not a specific method to detect the glycogen. PMID- 8345246 TI - [Study on the oral health status of schoolchildren in Korea]. AB - In 1992, dental health examination was conducted in three areas in Korea; Seoul (large city), Cheonan (rural city) and Cheongju (water fluoridated rural city). We also examined the children of Tokyo in Japan. The subjects were the schoolchildren in the 6th grade of primary school and the 3rd grade of junior high school, and the number of the subjects was 202 in Seoul, 191 in Cheonan, 164 in Cheongju and 152 in Tokyo. We compared the oral health status among these four areas using many indices such as the prevalence rate of dental caries and malocclusion, DMFT, DMFS, DI-S and P-M-A index. In Korea the children in Seoul showed the highest caries prevalence rate, DMFT and DMFS. The Cheonan children were average. The children in Cheongju had the lowest caries experience. The children in Tokyo had more dental caries than the Korean children in both school grades. The children in Tokyo had more gingivitis and malocclusion than the Korean children in the three areas. It was revealed that the oral health status of the Korean schoolchildren was much better than the Japanese children. And water fluoridation project in Cheongju was effective to prevent the dental caries especially in the 6th grade children. PMID- 8345247 TI - [Study on dental cement. Part 4. Protective effect of a newly designed light cured varnish on the vulnerability to water of glass polyalkenoate cement restorations]. AB - The protective effect of a newly designed light-cured varnish on the vulnerability to water of two kinds of glass polyalkenoate cement restorations was examined by determining the penetration depth of Ag ion into the set cement on the SEM pictures in comparison with those of the conventional varnish and a light-cured resin bonding agent. The protective effect of the experimental light cured varnish was perfect, while those of the conventional varnish and the light cured resin bonding agent were inferior to that. PMID- 8345248 TI - [Clinical and microbiological study concerning effects of scaling and root planing. 2. The effects of mechanical debridement until one year and of minocycline application topically]. AB - This study was performed to assess the effect of scaling and root planing clinically and microbiologically during one year. Nine patients with moderate to severe periodontitis were studied. After the process of plaque control, the selected single rooted teeth with 5mm probing depth were debrided mechanically under non-local anesthesia four times biweekly. Observing the results of the treated teeth until three months, the experimental teeth were divided into two groups. The standard of division was whether they showed good response to the mechanical debridement or not. Observation was continued until one year after the debridement according to the following criteria: 1. The sites which showed good responses at three months were continued to be observed biweekly. 2. The sites which showed no improvement at three months were applied the gel of minocycline (Periocline) four times biweekly. 3. The untreated sites used as control until three months received mechanical debridement four times biweekly. The following results were obtained: The sites that showed good responses to the mechanical debridement at three months were maintained in good condition continuously during one year. The topical application of Periocline was effective in reducing the inflammation and probing depth clinically and microbiologically until three months. PMID- 8345249 TI - Free tissue transfers to the upper limb. AB - 90 consecutive free tissue transfers to the upper limb have been performed in 75 patients (33 children and 42 adults) by one surgeon over a 3-year period. The average age for children was 5 years, and 25 years in adults. 17 transfers were performed as emergency or urgent procedures. The main indications were congenital and traumatic defects. Included in this series were 44 toe transfers, 28 lateral arm flaps and six functional muscle transfers. The overall success rate was 99%. The re-exploration rate was 5.6% with only one failure. There were no failures in children. PMID- 8345250 TI - Congenital pseudarthrosis of the ulna treated by free vascularized fibular graft: a case report and review of methods of treatment. AB - Congenital pseudarthrosis of the ulna is an extremely rare condition for which current surgical techniques have been unsatisfactory in restoring a normal two bone forearm. We report a case which was treated by excision of the ulnar pseudarthrosis and interposition of a free vascularized fibular graft with a skin island to monitor anastomotic patency. Forearm rotation has been restored and the potential for normal forearm growth has been preserved. PMID- 8345251 TI - Changes in carpal alignment following radial osteotomy for Kienbock's disease. AB - Changes in carpal alignment following radial osteotomy were studied in 30 patients with Kienbock's disease. The carpal height ratio and carpal-ulnar distance ratio were significantly less in wrists with Kienbock's disease than unaffected wrists. This observation implies proximal-ulnar translation of the capitate. In addition, the lunate-covering ratio increased significantly, reflecting radial translation of the lunate. Radial osteotomy corrected ulnar translation of the capitate and increased the radial translation of the lunate, thus increasing the lunate-covering ratio. The increased lunate-covering ratio is believed to increase the area of distribution of the axial load through the lunate by increasing the contact area with the radius. The satisfactory clinical outcome of radial osteotomy is believed to be due to this effect on carpal alignment. PMID- 8345252 TI - Aetiology of Kienbock's disease based on a study of the condition among patients with cerebral palsy. AB - Examination of 110 patients with cerebral palsy revealed a diagnosis of Kienbock's disease in six wrists in five cases. All had cerebral palsy of the mixed type with athetosis and high muscle tone. It is considered that the increased prevalence of Kienbock's disease in these cases was attributable to repeated minor trauma to the lunate from childhood due to high muscle tone across the wrist joint, together with negative ulnar variance. The high prevalence of Kienbock's disease observed in patients with cerebral palsy strongly suggests that repeated minor trauma together with negative ulnar variance is also the cause of Kienbock's disease in normal individuals. PMID- 8345253 TI - Functional outcome of upper limb tendon transfers performed in children with spastic hemiplegia. AB - Children with spastic hemiplegia often present with upper limb muscle imbalance. The purpose of this paper was to determine whether reconstructive surgery improved their functional ability. 17 children under the age of 16 years with spastic hemiplegia underwent reconstruction that included tendon transfers, tendon lengthenings and thumb metacarpophalangeal fusion. They were assessed pre operatively and at an average follow-up period of 2.6 years. Children's abilities were classified according to House's functional rating scale. Tendon transfers improved functional grading by two grades, from good passive assist to fair active assist. Improvement in the arc of wrist motion and forearm rotation was also seen. Parental satisfaction was high. Reconstructive surgery improved the functional abilities in this group of children with spastic hemiplegia. PMID- 8345254 TI - Early corrective surgery of the wrist and elbow in arthrogryposis multiplex congenita. AB - An early one-stage corrective surgical procedure for the elbow and wrist of patients suffering from arthrogryposis multiplex congenita is advocated. The procedure involves adequate proximal row carpectomy, tendon transfers to achieve a balanced wrist and a triceps to radius transfer for elbow flexion. Experience with 47 limbs showed that the best results were obtained in children operated on between 3 and 6 months of age. PMID- 8345255 TI - Macrodactyly in Proteus syndrome. AB - A case of Proteus syndrome in a 13-year-old boy with macrodactyly, hemihypertrophy, exostosis of the skull, epidermal naevi, palmar and plantar masses, and scoliosis is reported. Macrodactyly involving the left thumb was treated surgically. The usual findings in macrodactyly, hypertrophy of the digital nerves and proliferation of subcutaneous fat, were not observed in this case. Macrodactyly associated with Proteus syndrome should be distinguished from other forms of macrodactyly because of its poor prognosis and high rate of recurrence. PMID- 8345257 TI - Bilateral anomalous insertion of flexor pollicis longus. AB - A case of bilateral insertion of flexor pollicis longus to the proximal as well as the distal phalanges is reported. Initially, this case was diagnosed as congenital absence of the flexor pollicis longus, but surgery revealed an intact tendon, with the abnormality only present in the site of insertion. A survey of the literature on congenital abnormalities of flexor pollicis longus failed to reveal any reports of similar abnormalities. PMID- 8345256 TI - Camptodactyly caused by abnormal insertion and origin of lumbrical muscle. AB - A 12-year-old boy had camptodactyly of the little finger. Operative findings revealed an abnormal origin of the lumbrical muscle from the transverse carpal ligament, and abnormal insertion into the tendon sheath of the flexor digitorum superficialis tendon. No similar case has been reported in the literature. PMID- 8345258 TI - The anatomical course of the palmar cutaneous branch of the median nerve, including a description of its own unique tunnel. AB - In order to obtain a better understanding of the palmar cutaneous branch of the median nerve, dissections of 21 forearms from 12 fresh cadavers were done with loupe magnification. Discrete regions of potential surgical significance were identified, including an origin that can be as high as 11 cm proximal to the wrist crease, a radial position immediately after its origin so that it lies adjacent to flexor carpi radialis in the distal forearm, and the existence of an anatomical tunnel through the palmar aponeurosis. PMID- 8345259 TI - The results of secondary repair of 254 digital nerves. AB - 95 patients with 254 completely divided digital nerves were reviewed, on average, 12.4 (5-20) years after repair. There were 47 sharp and 48 blunt injuries. 45 injuries were at the level of the palm of the hand and 50 more distally. Secondary epineurial suture was used in 53, fascicular grafting in 37 and fascicular suture in five. Four sensory factors were assessed and evaluated quantitatively. Useful sensory function was recovered in 79.5% of the nerves operated on with epineurial or fascicular suture and in 56.3% with fascicular grafting. PMID- 8345260 TI - An open twin incision technique of carpal tunnel decompression with reduced incidence of scar tenderness. AB - We retrospectively compared a single curved incision for carpal tunnel decompression (group A, 29 wrists in 26 patients) with a twin incision technique (group B, 34 wrists in 30 patients), leaving an intact bridge of skin at the base of the palm. Patients in group B reported statistically significant subjective improvement in the early post-operative period, with fewer residual symptoms and earlier recovery of function compared to patients in group A. After a mean post operative period of 23 months, 5/29 wrists were symptomatic in group A compared to 1/34 wrists in group B at 13 months, but this was not statistically significant. The twin incision technique is easy to perform and allows rapid post operative recovery. The incidence of scar tenderness is reduced as palmar cutaneous branches of the median nerve are avoided. Because the distal portion of the transverse carpal ligament is divided under direct vision, this technique is not associated with any significant neurovascular complications. PMID- 8345261 TI - Acute calcification and carpal tunnel syndrome. AB - Carpal tunnel syndrome is a common diagnosis, and often there is no identifiable cause. We describe the case of a patient who developed acute symptoms secondary to calcification in the carpal tunnel. The patient was treated by decompression, and made a slow, but uneventful recovery. PMID- 8345262 TI - The association of peripheral nerve compression and reflex sympathetic dystrophy. AB - 35 patients who presented with reflex sympathetic dystrophy (RSD) are reported. Peripheral nerve compression was present in 86% of the patients (30). 50% of the patients (15) had a single nerve compression, and 50% had multiple nerve compressions. The high incidence of these entrapments should alert the clinician to check for this treatable problem early in the course of RSD. PMID- 8345263 TI - Objective improvements in algodystrophy following regional intravenous guanethidine. AB - 17 patients with established algodystrophy following trauma were treated with serial intravenous regional guanethidine blockade. Subjective improvement occurred in all cases. This improvement could be confirmed quantitatively using objective assessment criteria. The subjective and objective improvements demonstrated in each of the features of algodystrophy correlate closely (p < 0.001). There appears to be no difference in the effectiveness of one block compared to another in the same patient. PMID- 8345264 TI - Provisional fixation of distal radial osteotomies using the AO small external fixator. PMID- 8345265 TI - Treatment of volar instability of the metacarpophalangeal joint of the thumb by volar capsulodesis. AB - The metacarpophalangeal joint bears most of the stresses to which the thumb ray is subjected. Instability of this joint results in considerable functional impairment of the hand. Volar instability may be secondary to trauma, rheumatoid arthritis, or adduction spasms in cerebral palsy. The resulting hyperextension causes pain and weakness of pinch (Fig. 1). Various techniques have been described to correct this deformity. We prefer a volar capsulodesis as first described by Filler (1976), in which the whole volar plate is reinserted. Detailed knowledge of the complicated volar anatomy is essential. We have treated eight patients (two bilaterally) with this technique, all with satisfactory results. PMID- 8345266 TI - Intraosseous ganglia of carpal bones. AB - 25 patients with 26 intraosseous ganglia in carpal bones are described, 14 in the scaphoid and 12 in the lunate. In most cases, attention was drawn to the lesion when X-rays were performed after a recent injury to the wrist. Typically, they occurred eccentrically and were surrounded by a radio-dense rim of bone. In a few cases the cortex was breached but never expanded by the lesion. Curettage and bone grafting were performed only if symptoms persisted and no other source for the pain could be found. Most contained the typical jelly-like material also found in soft tissue ganglia and the histology showed an identical structure. A suggested format for the management of these lesions is presented. PMID- 8345267 TI - Ewing's sarcoma of the thumb. PMID- 8345268 TI - Paronychia: a mixed infection. Microbiology and management. AB - Cultures of paronychia of the fingers have grown aerobic and anaerobic bacteria. Each was recovered individually in only about a quarter of the patients and a mixed aerobic/anaerobic flora was isolated in half of the patients. The predominant anaerobic organisms were Gram-positive anaerobic cocci, Bacteroides species and Fusobacterium species. The predominant aerobic organisms were Staphylococcus aureus, gamma-haemolytic streptococci, Eikenella corrodens, group A beta-hemolytic streptococci, alpha-hemolytic streptococci, and Klebsiella pneumoniae. Candida albicans was recovered in about 15% of the cases. The management of this infection is discussed. PMID- 8345270 TI - Dupuytren's disease: a legacy of the north? AB - This study identifies four miracle cures set in Orkney and Iceland in the 12th and 13th Centuries and recorded in the sagas of the earls of Orkney and the bishops of Iceland, in which the condition of the hand which was healed bears a resemblance to Dupuytren's disease. The possibility that one hand was cured by traumatic rupture of this condition and another treated by palmar fasciotomy is discussed. PMID- 8345269 TI - Cysticercosis of the flexor digitorum profundus muscle producing flexion deformity of the fingers. AB - Selective flexion deformity of the middle and ring fingers resembling a mild type of Volkmann's contracture resulted from Cysticercus cellulosa infection within the deep flexor muscle of the forearm in a middle-aged woman. Excision of the fibrotic segment of the muscle and tenodesis of all the flexor profundus tendons restored normal range of motion to these fingers. Vascular compromise in addition to the inflammatory response to the infection were considered causes for the deformity. There is no previous report of this kind in the literature. PMID- 8345271 TI - Dupuytren's disease in identical twins. AB - The aetiology of Dupuytren's disease remains unknown, although hereditary and environmental influences have been implicated. Previous reports have suggested that identical twins will develop identical contractures. This paper reports two pairs of identical twins, in each of which only one twin has evidence of Dupuytren's disease. This demonstrates that an appropriate genetic background is inadequate of itself for the development of Dupuytren's disease without a suitable, and as yet unknown, environmental trigger. PMID- 8345272 TI - Capsular tissues of the proximal interphalangeal joint: normal composition and effects of Dupuytren's disease and rheumatoid arthritis. AB - Three fibrocartilages associated with the proximal interphalangeal joint are described--at the attachment of the central slip to bone, within the slip where it passes over the joint, and the volar plate. Material was obtained at surgery following trauma, Dupuytren's disease and rheumatoid arthritis. The fibrocartilages were structurally distinct and immunolabelled differently with monoclonal antibodies to extracellular matrix components. All fibrocartilages from normal and Dupuytren's fingers contained chondroitin and keratan sulphate. Type II collagen was present in all attachment zones, although there was little in rheumatoid fingers. It was also present in the dorsal hood of some normal fingers, but not in pathological specimens or the volar plate. The results show that the fibrocartilages are dynamic tissues whose composition varies according to function and use, and changes in disease. PMID- 8345273 TI - Wrist arthrodesis in rheumatoid arthritis. A comparison of two methods of fusion. AB - 17 wrists were arthrodesed in 13 patients with severe wrist disease due to rheumatoid arthritis. Eight fusions in seven patients were carried out using a radial sliding bone graft technique whilst nine fusions in nine patients were undertaken using a third tubular AO plate. Subjective, objective and radiological assessments confirmed the efficacy of both methods but indicated a shorter period of post-operative immobilization for patients treated using the AO plate fixation technique. The importance of this is discussed. PMID- 8345274 TI - Long-term results of Swanson silastic arthroplasty in the rheumatoid wrist. AB - We report a long-term follow-up of 6 to 11.8 years (mean = 8 years) of our first 50 Swanson wrist arthroplasties. All patients had long standing sero-positive rheumatoid arthritis with a mean age of 48 years. A detailed clinical and radiologic assessment was carried out on all the wrists. There was excellent sustained pain relief (mean score = 1.7) with improved activities of daily living. A mean range of wrist movement of 25 degrees of extension and 31 degrees of flexion was obtained. The prosthetic fracture rate was 22% of which 14% were symptomatic and needed re-operation. Carpal collapse was seen in all wrists, but was often symmetrical and accompanied by radial new bone formation on X-ray (86%). We feel that our long-term results justify the continued selective use of the Swanson wrist in the low-demand patient with quiescent disease who desires pain-free limited mobility and sophisticated grasp. PMID- 8345275 TI - The Guildford elbow. AB - The Guildford elbow is a new unconstrained elbow arthroplasty. From 1985 to 1991, this arthroplasty was used in 24 patients with rheumatoid arthritis. The patients were reviewed after an average of 28 months (4-59 months). Good to excellent results were obtained in 95% regarding pain relief and functional improvement. Complications were few, with only one case of clinical loosening and three of radiological loosening. Ulnar nerve hypo-aesthesia was common but did not jeopardize the final result in any patient. PMID- 8345276 TI - The relationship between handedness, mechanism of injury and which hand injured. PMID- 8345277 TI - The economic impact of hand injuries. AB - The socio-economic effect of 156 hand injuries was studied prospectively. The average cost per injury was IR 474.28 pounds of the more serious injuries utilized two-thirds of the resources and resulted in 83% of the days lost from work. In the working population approximately 50% of hand injuries occurred at work. In assessing the economic impact of hand injuries, labour costs account for 55 to 65% of costs. Amputation and complicated laceration were the most costly and resulted in more days lost at work. Injuries at work result in greater costs because they involve more serious injuries, and because workers requiring manual skills need a higher level of hand rehabilitation to return to work. Unless the labour costs are taken into account, the true impact of hand injuries is greatly underestimated. PMID- 8345278 TI - V-Y advancement of the entire volar soft tissue of the thumb in distal reconstruction. AB - The commonly used variant of Moberg's advancement flap for thumb reconstruction requires a skin graft to reconstruct the proximal thumb defect after advancing the flap. A modification has been described previously which allows direct closure of this proximal defect by incorporation of the V to Y principle into the design of the proximal part of the flap. A variant of the V-Y Moberg flap is presented and its advantages discussed. PMID- 8345279 TI - The value of radiographs and bone scintigraphy in suspected scaphoid fracture. A statistical analysis. AB - The role of radiography and bone scintigraphy in the diagnostic management of suspected scaphoid fracture is controversial. Two strategies were compared for patients with initial negative radiographs: repeated radiography versus selective bone scintigraphy. Using the known positive predictive value of scintigraphy, the sensitivity and specificity of both diagnostic strategies were evaluated in a series of 78 consecutive patients. The kappa value for initial radiographs was 0.76 but decreased to 0.5 for follow-up radiographs. Similarly, sensitivity decreased from 64% to 30% in follow-up radiographs. Specificity of the bone scan was 98%. The best diagnostic strategy in the management of clinically suspected scaphoid fractures consists of initial radiography followed by bone scintigraphy in patients with negative radiographs. PMID- 8345280 TI - Erik Moberg (1905-1993). PMID- 8345281 TI - Acute carpal tunnel syndrome due to pseudogout. PMID- 8345282 TI - Aspiration of ganglia. PMID- 8345283 TI - Claw-finger correction. PMID- 8345284 TI - Studies of topical carbonic anhydrase inhibitors: ocular hypotensive effect of thiadiazole derivatives. AB - A series of thiadiazole derivatives were topically applied in gels or suspensions to rabbits to determine their ocular hypotensive effect. As a result, the compounds with higher corneal permeabilities showed stronger effect in lowering IOP. In addition, gels also caused stronger effect than suspensions. Different concentrations of gel preparations produced diverse ocular hypotensive effects. A linear relationship between the integrated IOP response and logarithm concentration of inhibitor was found. It is proposed that the ocular hypotensive effect was attributed to the level of inhibitor in ciliary body. PMID- 8345285 TI - The presence of sigma-receptors in the lacrimal gland. AB - Applying the technic of S.A. Wolfe et al. [Endocrinology, 124, 1160-1172, 1989], we have established the presence of sigma receptors in isolated, but intact, lacrimocytes excised from main lacrimal gland tissue of the New Zealand white rabbit. 3H-Haloperidol was used as the ligand (0.5-2500 nM), in the presence of spiperone. From a Scatchard plot, a single binding site was statistically chosen over two sites for a majority of the data associated with the intact lacrimocytes. Kd (71.0 +/- 46.4 nM) and Bmax (588.2 +/- 166.7 fmol/mg of protein) values showed lower binding affinity but a similar density of sigma sites in rabbit lacrimocytes when compared to published results obtained for rat exocrine glands and brain tissue. Using the technic of McCann and Su [J. Pharm. Exp. Therap., 257, 547, 1991], membrane suspensions of the sigma receptor were also prepared and tested for binding to radioligands, 3H-DTG, as well as 3H haloperidol. A Scatchard plot revealed two binding sites for 3H-DTG and one binding site for 3H-haloperidol. The high affinity site for 3H-DTG yielded a Kd of 1.04 +/- 0.64 nM, whereas, Bmax was 135.9 +/- 11.62 fmol/mg of protein. The low affinity site gave a Kd = 75.3 +/- 26.8 nM and Bmax = 344.0 +/- 222.0 fmol/mg of protein. The weaker site is suspected to be intracellular. IC50 values were determined for N,N-disubstituted arylphenylalkylamines (Kd approximately low nM). PMID- 8345286 TI - Preliminary evaluation of a series of amphiphilic timolol prodrugs: possible evidence for transscleral absorption. AB - A series of amphiphilic esters of timolol malonate (octanoyl, decanoyl, dodecanoyl, myristoyl and palmitoyl timolol) were tested in rabbits for their capacity to antagonise the isoproterenol-induced ocular hypotension, using timolol maleate as reference standard. The most active prodrug, palmitoyl timolol malonate (PTM) was also evaluated for its capacity: (a) to decrease IOP in a model of bethamethasone-induced ocular hypertension, and (b) to permeate "in vitro" through rabbit corneal tissues. PTM, the prodrug with the longest aliphatic chain and therefore the greatest amphiphilic/lipophilic character, showed "in vivo" significant activity differences with respect to timolol maleate: the beta-antagonism was more important at earlier and later experimental times, and the IOP decrease was more marked at longer times. The prodrug, however, showed "in vitro" an inferior corneal permeability when compared with timolol maleate. The significant differences observed for the beta-antagonism of PTM at earlier times of the test might be attributed to transscleral absorption, due to the physicochemical characteristics of the prodrug, while the prolonged action (also observed in the IOP-depression test) might be due to sustained release, resulting from accumulation of the prodrug in the corneal epithelium. The present preliminary results are indicative of the potentiality of amphiphilic properties in a prodrug molecule. PMID- 8345287 TI - Inhibitory effects of tetrandrine on bovine serum albumin-induced uveitis in rabbits. AB - Experimental uveitis was successfully induced in rabbits by bovine serum albumin (BSA). Tetrandrine (Tet), 50 mg/kg/d i.p., and dexamethasone (Dex), 5 mg/kg/d i.p., for 8 d showed marked inhibition of uveitis in rabbits. Eight d after drug administration, ocular inflammation was markedly inhibited. The maximum inhibitory rate of Tet and Dex was 48.9% and 56.0%, respectively. The protein content of the aqueous humor (PAH) was reduced significantly; phytohemagglutinin (PHA)-induced peripheral T lymphocyte transformation of 3H-thymidine (3H TdR) incorporation was suppressed markedly; and serum circulating immune complexes (CIC) also were reduced. Four d after Dex withdrawal, ocular inflammation, PHA and CIC rose again, but these parameters were not changed after Tet withdrawal. These results suggest that Tet is an effective inhibitory agent on BSA-induced uveitis in rabbits. The inhibiting action may be related to the suppression of cellular and humoral immune function and, unlike Dex, Tet did not produce withdrawal rebound. PMID- 8345288 TI - Intraocular pressure response to loteprednol etabonate in known steroid responders. AB - The continuing development of ophthalmic steroids has resulted in compounds that have a low tendency to raise intraocular pressure (IOP). Preliminary clinical data have suggested that loteprednol etabonate (LE) 0.5% suspension may not elevate IOP while having promise as a potent topical ophthalmic steroid. This study was designed to evaluate the comparative potential of topical LE and prednisolone acetate (PA) to raise IOP in a population of individuals known to be steroid responders. The study used a double-masked, randomized, single eye, crossover design comparing LE 0.5% and PA 1.0%. Subjects instilled 1 drop of the assigned medication 4 times daily while awake, and follow-up examinations occurred on days 14, 28, and 42. Following a washout period of at least 14 days, subjects entered the second phase of the study, which was identical to the first phase, except that subjects received the alternate study medication. The mean IOP in the LE group increased from 17.4mm Hg at baseline to 21.5mm Hg at day 42 (p > 0.05), while in the PA group the mean IOP increased from 18.1mm Hg at baseline to 27.1mm Hg at day 42 (p < 0.05). There were no serious, severe, or clinically significant events in either group, and LE's effect on IOP was differentiable from that of PA. LE has less effect on IOP when compared to the IOP response induced by PA. LE may become a clinically useful ocular steroid with a favorable IOP-safety profile. PMID- 8345289 TI - Levels of vancomycin in aqueous humor after topical eye drops administration. AB - Vancomycin is an antibiotic which is especially active against Gram positive bacteria. At present, numerous infections of the anterior segment of the eye are caused by the Staphilococcus aureus and epidermis. Strains which are resistant to methicilin are more and more frequent and for this reason Vancomycin is becoming the antibiotic of choice to combat these infections since no resistance of the Staphilococcus to it has been demonstrated. The authors evaluated the levels of Vancomycin in aqueous humor after the administration of topical eye-drops. For the first two hours after the last administration, levels of 0.52 micrograms/ml were detected. These inhibit the growth of the majority of bacteria sensitive to Vancomycin. Between two and four hours, the levels decreased to 0.15 micrograms/ml; these are therapeutic levels for a large number of Gram positive bacteria. From four hours after the last administration, these levels are undetectable. Due to the success of its penetration, topical administration of Vancomycin should be considered as a therapeutic modality against infections by gram positive bacteria of the anterior segment. The ideal guideline for administration would be one drop every two hours, especially if the infection is severe. In this way, subconjunctival injection could be avoided. PMID- 8345290 TI - The effects of photofrin on human Tenon's capsule fibroblasts in vitro. AB - Pharmacological agents that modulate the wound healing process by inhibiting fibroblast proliferation may improve the success of proliferative vitreoretinopathy and glaucoma filtration surgery and may have applications in other surgical fields. It is possible that light-absorbing chemicals can be used to cause photo reactions in proliferating fibroblasts as a means of controlling this wound healing process. We present the effects of photofrin porfimer sodium (serial tenfold dilutions 1000-0.00001 micrograms/ml) on human fibroblasts from Tenon's capsule in vitro, with and without photoactivation with Argon green laser (700 mW for 1 and 5 minutes) and with bright sunlight (for 1 and 5 min). The cell density was measured on day 2 by 3H-thymidine uptake and on day 9 by means of a coulter counter, and optical density was measured in terms of the activity of the enzyme hexosaminidase. Each experiment was performed three times in quadruplicate. The counts were averaged for each drug concentration and mean cell count with a standard error as well as the 50% inhibitory doses (ID50s) were calculated. Photofrin demonstrated an inhibitory dose response curve (dark toxicity) to human fibroblasts. Concentrations greater than 100 micrograms/ml of photofrin alone completely inhibited cell growth. Concentrations less than 0.01 micrograms/ml did not have any effect on fibroblast proliferation. There was no significant log dose shift of the inhibitory effect of photofrin with the exposure to either sunlight or Argon laser. Photofrin may be used as a cytotoxic agent alone but does not appear to be activated by light to modulate subconjunctival fibroblast proliferation within the laser parameters used. PMID- 8345291 TI - Effects of dopamine antagonists on retinal B-wave recovery after retinal ischemia. AB - Retinal ischemia was developed by occlusion of the central retinal artery for 30 minutes. The artery was reperfused thereafter, and the recovery of the b-wave amplitude was determined as an indication of the recovery of retinal function after ischemia. Following ischemia, it was found that dopamine antagonists, including chlofluperol, metoclopramide, trifluperol and droperidol, increased in b-wave amplitude recovery significantly over the control b-wave recovery. Similar effects were observed with haloperidol and loxapine, but to a lesser extent. The results correlated well with the improvement of retinal blood flow by these dopamine antagonists (4,5). Neither floropipamide, a dopamine antagonist, nor bromocriptine, a dopamine agonist, affected the b-wave recovery after ischemia. These results also correlate well with the inability of these agents to increase the retinal blood flow measured by the microsphere technique (4,5). These findings suggest that most of the dopamine antagonists, with the exception of floropipamide, could be used for the treatment and/or prevention of ischemic retinopathy. PMID- 8345292 TI - Studies of carbonic anhydrase inhibitors: physicochemical properties and bioactivities of new thiadiazole derivatives. AB - A series of thiadiazole derivatives of carbonic anhydrase inhibitors were prepared and their physicochemical properties and pharmacological activities such as corneal permeabilities, inhibition of carbonic anhydrase activities were evaluated. The solubilities and pKa values were determined in varied pH of phosphate buffers at 35 degrees C after equilibrium. Intrinsic solubility and pKa value were calculated from the plot of solubility versus the reciprocal of hydrogen ion concentration. The distribution coefficient was determined in the system of octanol/pH 7.65 phosphate buffer. As a result, the sigma (Hammett constant) and pi (hydrophobic substituent constant) values of substituents were found to be correlated to the logarithm of Ka and partition coefficient. Corneal permeabilities of the analogue were determined in a specially designed diffusion cell using excised rabbit cornea, which ranged from 1.32 x 10(-5) (compound II) to 3.48 x 10(-7) cm/sec (compound VI). Compound with high permeability might be expected to be absorbed well after topical administration into the eye. The methodology of pH-stat was used to determine the inhibition of the carbonic anhydrase activity of the analogue. The IC50 values of the analogue around 10(-8) M as determined were less than that of acetazolamide. The results suggest that the analogue had good pharmacological activity. Finally, an equation for quantitative structure-activity relationship was established for the analogue, which is as follows: [formula: see text] PMID- 8345293 TI - Vestibular testing: the current position. PMID- 8345294 TI - A review of the definition, terminology and pathology of aural cholesteatoma. AB - Despite a considerable amount of discussion and research in the course of many years, aural cholesteatoma has remained a matter of controversy. This review concerns only the definition, terminology and pathology of this common and severe disease. PMID- 8345295 TI - Clinical otosclerosis and auditory exostoses in ancient Europeans (investigation of Lithuanian paleoosteological samples). AB - The purpose of this investigation was to establish the incidence of clinical otosclerosis and auditory exostoses in Lithuanian paleopopulations. The total sample consists of 4080 skulls, dating from the Neolithic to the C17th-C18th A.D., investigated visually, under magnification and radiologically. Eight cases of clinical otosclerosis and 22 of auditory exostoses were identified. The general epidemiology of otosclerosis (0.19 +/- 0.08 per cent) was established to be similar to contemporary populations. This suggests that there are no new aetiological factors attributable to our modern society. Clear diminution of the incidence of auditory exostoses from the 1st to the 2nd millenium A.D. (3.46 +/- 0.76 per cent, against 0.06 +/- 0.04 per cent, p < 0.001) and definite sexual differences (males: 1.21 +/- 0.28 per cent; females: 0.17 +/- 0.10 per cent, p < 0.001) were also noted. In general, auditory exostoses were found much more frequently than in recent populations. PMID- 8345296 TI - Congenital cerebrospinal fluid fistula through the inner ear and meningitis. AB - Congenital deformities of the labyrinth of the inner ear can be associated with a fistulous communication between the intracranial subarachnoid space and the middle ear cavity. We describe seven such cases, six confirmed by high resolution CT and one by postmortem histological section. The seven patients all presented with meningitis although a cerebrospinal fluid fistula was demonstrated at subsequent surgery or postmortem. The lesions were bilateral in three patients, unilateral in three and probably bilateral in the postmortem case although only one temporal bone was obtained. In every case there was a dilated sac instead of the normal two and a half turn cochlea on the affected side and this was confirmed at surgery. The demonstration of the basal cochlear turn is of paramount importance in any deaf child presenting with meningitis. A true Mondini deformity with a normal basal turn and some hearing is not at risk of developing a fistula. PMID- 8345297 TI - Sensory interaction testing in platform posturography. AB - Mostly techniques measuring the vestibulo-ocular reflex (VOR) have been used for the evaluation of patients with dizziness problems. Some investigators, however, have also tried to take into account the vestibulospinal reflex (VSR). So recording techniques for the Romberg-test have been proposed and called posturography (PG). By interfering with the visual and proprioceptive sensory inputs during this PG-testing one tries to find out how 'sensory interaction' is organized in the balance performance of the patient examined. To interfere with vision, closure of the eyes has been commonly used and to interfere with proprioception, the patient can be put on foam-rubber, which makes the contribution of the foot-ankle proprioception less adequate. These interferences are applied once separately and once combined. The degree of 'abnormality' is assessed by a score-system for parameters surface (S) and velocity (V), which measure the postural sway. A comparison of tests with and without influence on the sensory inputs gives an idea of the sensory interaction. Patients with peripheral vestibular disorders were examined: patients with BPPV, with spontaneous vertigo attacks and with a sudden vestibular deficit. When applying this evaluation technique different formulae or patterns can be found. Firstly complete normal evaluation, which means that there is no influence of the vestibular disturbance upon the PG results. Secondly a normal balance when using all available sensory information, but disturbed balance as soon as one of the sensory inputs is influenced by the test conditions. Thirdly striking destabilization when closing the eyes. Fourthly striking destabilization when misleading the ankle and foot proprioceptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345298 TI - Osseointegrated implants in the management of childhood ear abnormalities: the initial Birmingham experience. AB - Over a four-year period 72 children with ear abnormalities have been referred for assessment by the extraoral osseointegrated implant team at The Queen Elizabeth Hospital, Birmingham. Thirty-two children have been judged suitable for rehabilitation. Twelve children have completed rehabilitation using bone-anchored hearing aids and/or auricular prostheses. Two fixtures (seven per cent of those loaded) have dislodged and required replacement. Audiological assessment of the bone-anchored hearing aid users shows only small improvements in their aided thresholds, compared to thresholds obtained with their previous aid. However all now have thresholds of 30 dB(A) or better and report a marked improvement in sound quality. When surveyed, hearing aid and prosthesis users report high levels of satisfaction with this form of rehabilitation. The technique adds a new dimension to the management of children with aural anomalies. The approach and results of a multidisciplinary programme are reported. PMID- 8345299 TI - A new technique using cultured epithelial sheets for the management of epistaxis associated with hereditary haemorrhagic telangiectasia. AB - A new technique for the treatment of severe epistaxis associated with hereditary haemorrhagic telangiectasia is described. The nasal septum and inferior turbinates, surgically denuded of respiratory epithelium, were grafted using autografts of cultured epithelial sheets derived from buccal epithelium. All patients upon whom this technique has been used have shown considerable lessening in the frequency and severity of their epistaxes although two patients received grafts on two occasions, in each case approximately three months apart. It is postulated that a nasal lining of stratified squamous epithelium is likely to be more resistant to trauma than the normal respiratory type, and this is supported by the observation that bleeds very seldom occur from the oral cavity in this syndrome. PMID- 8345300 TI - Risk factors involved in stomal recurrence following laryngectomy. AB - Stomal recurrence after surgery for laryngeal tumours is an extremely serious complication, with a dismal prognosis despite aggressive surgical therapy or high dose irradiation. Data from 209 patients who underwent total laryngectomy for cancers of the larynx and hypopharynx were retrieved from the registry of the Department of Otorhinolaryngology at the Hospital 'Virgen de las Nieves' of Granada. Stomal recurrence developed in 8.1 per cent of them (17 cases). We analysed several parameters from each case: first, those parameters significantly associated with stomal recurrence were detected, and secondly, a logistic regression analysis was done. Three factors were found independently related to stomal recurrence: T-staging, site of the primary tumour and prior tracheostomy. Together with a review of the literature, we discuss our findings and a proposal for management of the high risk patient. PMID- 8345301 TI - The relationship between SIgA and chronic granular pharyngitis. AB - A survey of the SIgA content in saliva, serum and pharyngeal mucosa with lymphoid tissue (PMLT) of chronic granular pharyngitis patients was conducted by a double antibody PEG radio-immune method. These data were compared with those from a healthy control group. Result shows that SIgA in patients with chronic granular pharyngitis had dissociation of saliva, serum and PMLY. There was low salivary SIgA level but higher levels in serum and PMLT. These data suggest that the saliva and serum immunoglobulin pools are under separate regulation. PMID- 8345302 TI - The globus syndrome: value of flexible endoscopy of the upper gastrointestinal tract. AB - Flexible endoscopy of the upper gastrointestinal tract usually does not form part of the primary diagnostic evaluation of the globus syndrome. In a prospective trial, a flexible endoscopy was performed in 51 globus patients with normal results of the laryngologic and radiographic examination. Pathologic findings requiring therapy were diagnosed in 70.6 per cent of cases. The most frequent findings were reflux oesophagitis (n = 24; 47 per cent) and hiatal hernia (n = 25; 49 per cent). In 16 cases (31.4 per cent) these were accompanied by other pathologic lesions. A total of 32 patients (62.7 per cent) suffered from oesophageal diseases as sole aetiologic factors of the globus syndrome, which led us to postulate a causative relationship in these cases. Flexible endoscopy therefore can contribute significantly to the differential diagnosis of the globus syndrome. It must be kept in mind, however, that there is a 'blind zone' for endoscopic assessment in a region of the hypopharynx, thus some indications may require rigid endoscopy. PMID- 8345304 TI - Parathyroid adenomas: pre-operative localization with ultrasound combined with fine-needle biopsy. AB - Sixteen patients with biochemically proven primary hyperparathyroidism (PHPT) underwent ultrasonography (US), fine-needle aspiration (FNA) for cytologic sampling (n = 9), or intact parathormone assay (n = 3) before operation (n = 15) in order to determine the accuracy of the methods. Pre-operative US was found sensitive (100 per cent), but two thyroid lesions were initially diagnosed as parathyroid tumours by US (i.e. false positives). Parathyroid cells were detected in six cytologic specimens, one sample was insufficient and another inconclusive, while one was diagnosed as thyroid tissue. Parathormone assay revealed a high hormone content in all three patients who underwent the procedure. We conclude that US is sufficiently sensitive to detect enlarged parathyroid tumours. Specificity can be improved by US-guided FNA for cytology or parathormone assay prior to neck exploration. PMID- 8345303 TI - The management of multiple paraganglioma of the head and neck. AB - During the years 1984 to 1991, of 32 patients who had one large glomus or carotid body tumour, six were found to have other paragangliomas. Excluded from the above total of 32 are patients whose only lesion was a solitary glomus tympanicum. No two patients had identical problems and no pattern emerged on which patient management in any particular case could be based. The major problems associated with the tumours themselves and their treatment is the risk to hearing and the lower cranial nerves. Individual cases and their treatment are discussed. PMID- 8345305 TI - Tympanic membrane ossification. AB - Ossification of the tympanic membrane after myringoplasty is recorded for the first time. Myringoplasty was performed for closure of a perforation which followed the surgical treatment of otitis media with effusion and had included the insertion of a long-term T-tube. PMID- 8345306 TI - Cerebellopontine angle lipoma. AB - A case of a cerebellopontine angle lipoma is presented with a typical clinical, audiometric and radiological features of an acoustic neuroma. The correct pre operative diagnosis was elusive even with the aid of magnetic resonance imaging. PMID- 8345307 TI - Polypoid lipoma of the palatine tonsil. AB - A polypoid, pedunculated tumour of the left palatine tonsil was incidentally detected in a 42-year-old female. It was composed of mature fat and was covered by a nonkeratinizing squamous epithelium with an underlying rim of fibrous tissue. The literature on tonsillar lipoma is reviewed and the differential diagnosis of polypoid lesions of the tonsil is discussed. PMID- 8345308 TI - Mycobacterial infection of the parotid gland: an unusual cause of parotid swelling. AB - Six cases of mycobacterial infection of the parotid gland are reviewed. All six cases presented solely with a slowly enlarging parotid swelling clinically indistinguishable from a parotid tumour. All of the swellings required surgical removal, superficial parotidectomy in four cases, and enucleation in two cases to obtain a definitive diagnosis. PMID- 8345309 TI - Laryngeal imaging by computerized tomography and magnetic resonance following radiation therapy: a need for caution. AB - For patients with laryngeal tumours, the use of computerized tomography (CT) or magnetic resonance imaging (MR) may facilitate accurate staging by the demonstration of cartilage invasion or tumour extension to areas such as the pre epiglottic space. The role of imaging in the follow-up of patients after radiotherapy, however, has not been examined. A prospective study of 18 patients undergoing laryngectomy was performed. The results of pre-operative CT and MR imaging were correlated with the pathological findings from whole organ axial sections of the laryngeal specimens. In five patients (28 per cent) both CT and MR images were significantly impaired by movement artefact. In the eight patients without previous radiotherapy, seven had adequate quality imaging and both CT and MR accurately demonstrated the site, size and extent of laryngeal tumour. In eight of the ten patients following radiation therapy the presence of tumour was correctly identified, however there was a poor correlation between the imaging and pathological findings. Two patients had radionecrosis alone. Neither CT nor MR imaging could differentiate between radionecrosis and recurrent tumour. PMID- 8345310 TI - Temporal bone histopathology of open mastoidectomy cavities. AB - Open cavity mastoidectomy remains the principle surgical treatment of middle ear cholesteatoma in the United Kingdom. A significant proportion of mastoid cavities are prone to intermittent or continuous discharge. In this study the temporal bone histopathology of four patients who had undergone open cavity mastoidectomy is presented. Cavities were predominantly lined with stratified keratinizing squamous epithelium. Residual air cells were obliterated by fibrous tissue, with no evidence of persistent respiratory epithelium. Where inflammatory changes were found, these consisted of areas of granulation tissue in association with epithelial ulceration. Residual cholesteatoma pearls (epidermoids) were not associated with significant inflammatory changes. PMID- 8345311 TI - A comparison of health care costs for chiropractic and medical patients. AB - OBJECTIVE: To compare the health care costs of patients who have received chiropractic treatment for common neuromusculoskeletal disorders with those treated solely by medical and osteopathic physicians. DESIGN: Retrospective statistical analysis of 2 yr of claims data on various categories of utilization and insurance payments for a large national sample of patients. SETTING: Ambulatory and inpatient care. PATIENTS: A total of 395,641 patients with one or more of 493 neuromusculoskeletal ICD-9 codes. OUTCOME MEASURES: Hospital admission rates and 10 categories of insurance payments. RESULTS: Nearly one fourth of patients were treated by chiropractors. Patients receiving chiropractic care experienced significantly lower health care costs as represented by third party payments in the fee-for-service sector. Total cost differences on the order of $1,000 over the 2-yr period were found in the total sample of patients as well as in subsamples of patients with specific disorders. The lower costs are attributable mainly to lower inpatient utilization. The cost differences remain statistically significant after controlling for patient demographics and insurance plan characteristics. CONCLUSIONS: Although work is in progress to control for possible variations in case mix and to compare outcomes in addition to costs, these preliminary results suggest a significant cost-saving potential for users of chiropractic care. The results also suggest the need to reexamine insurance practices and programs that restrict chiropractic coverage relative to medical coverage. PMID- 8345312 TI - Abnormal joint mechanics and the proteoglycan composition of normal and healing rabbit medial collateral ligament. AB - OBJECTIVE: This study investigated the influence that abnormal joint mechanics may have upon the biochemical composition of the joint's own soft tissue holding elements. DESIGN: The investigation used an animal model of ligament injury, the rabbit medial collateral ligament (MCL). The proteoglycan component of the ligament extracellular matrix was extracted, purified and characterized. INTERVENTIONS: The experimental groups consisted of: a) a control group consisting of the MCL from both right and left knees of six animals that had not undergone surgery; b) a group (healing gap injury) of six MCL from right knees in which a segment of tissue had been excised from the anterior cruciate and the MCL of the right knee 3 wk prior to sacrifice; and c) a third group (contralateral gap injury) comprised of the MCL from the six left knees of the same gap injury animals. OUTCOME MEASURES: The MCL water content, total proteoglycan content, hexose and hexuronate-containing proteoglycan and proteoglycan electrophoretic mobility were determined for each group studied. RESULTS: The healing gap injury MCL was found to have a higher water content, a higher total proteoglycan content and a higher proportion of aggregating proteoglycan than MCL from control animals. The nonaggregating proteoglycan fraction from the contralateral MCL (group 3) had a greater electrophoretic mobility and probably, therefore, a smaller molecular weight than that found in the MCL from the same knee of control animals. CONCLUSIONS: Since MCL healing took place in an abnormal mechanical environment, these results suggest that joint biomechanics may be an important factor in mediating connective tissue proteoglycan composition. PMID- 8345313 TI - Responsiveness of leg alignment changes associated with articular pressure testing to spinal manipulation: the use of a randomized clinical trial design to evaluate a diagnostic test with a dichotomous outcome. AB - OBJECTIVE: A study was undertaken to assess the stability of leg alignment reaction to a pressure challenge and its responsiveness to an adjustive intervention. DESIGN: Prospective, double-blind clinical trial of a diagnostic test. SETTING: Laboratory: Center for Technique Research. PARTICIPANTS: Forty-two chiropractic college students, faculty and staff. INTERVENTIONS: A high-velocity, low-amplitude, short lever adjustment of a single vertebra from among C1 and T3 T7; or a sham adjustment similar to a manual diagnostic pressure test at C1, T3 T7 or T9-T10. MAIN OUTCOME MEASURES: Leg alignment reactivity: An increase in leg alignment discrepancy (yes or no) following a metered pressure challenge to a vertebra. RESULTS: On average, stability was poor at T3-T7 (Kappa = 0.04), moderate at C1 (K = 0.47), and fair for sham pressure tests (K = 0.30). Responsiveness: The proportion of positive baseline leg alignment reactions that responded (became negative) to sham adjustment was 95% at T3-T7 and 55% at C1. Further analysis was untenable since too few vertebrae were implicated for an adjustment. CONCLUSIONS: For the population investigated, the majority of the responsiveness of the leg alignment diagnostic test to a rotatory adjustment appears to be a diagnostic illusion (i.e., background noise unrelated to a treatment intervention). Further research with different subject populations, regions of investigation, leg alignment measurement techniques and vertebral challenge techniques are indicated. PMID- 8345314 TI - Determination of lactate threshold by respiratory gas exchange measures and blood lactate levels during incremental load work. AB - OBJECTIVE: The purpose of this investigation was the determination of the lactate threshold (LT) by selected respiratory gas exchange measures and venous blood lactate levels during incremental load work on a mechanically braked cycle ergometer. DESIGN: Repeated measures design. SETTING: Human Performance Laboratory. PARTICIPANTS: Eight healthy trained soccer players (mean age 21.9 +/- 3.0 yr, mean VO2max = 59.2 +/- 3.6 ml.kg.min-1). OUTCOME MEASURE: Subjects conducted two incremental load work tests. Incremental load work was increased by 1 kilopond (kp) every third minute at 60 rpm until voluntary exhaustion. Blood samples from a forearm vein were collected during the second trial (T2) only and analyzed for lactic acid [LA-]. RESULTS: One-way analysis of variance (ANOVA) with repeated measures indicated no statistically significant difference between the two tests for maximal oxygen uptake (VO2max), maximal carbon dioxide production (VCO2max), maximal heart rate (HRmax), maximal pulmonary ventilation (VEBTPSmax) and lowest ventilatory equivalent of oxygen (VE/VO2), respectively; however, there was a significant difference among the oxygen uptake (VO2) values at the LT for the four determination methods. In our subjects, the measured (mean +/- SD) VE/VO2 in relation to VO2 for the first trial (T1) of 22.9 +/- 1.9 occurred at VO2 of 1.27 +/- 0.8 l.min-1. The lowest VE/VO2 and the onset of [LA-] accumulation calculated from individual exponential equations relating VE to VO2 yielded VO2 values of 1.77 +/- 0.18 and 1.74 +/- 0.25 l.min-1 for the T2. Utilizing natural log for lactate ln [LA-] to natural log for ln (VO2) equations, the LT for T2 occurred at VO2 of 1.30 +/- 0.70 l.min-1. CONCLUSION: LT was best predicted by the measured lowest VE/VO2 and the plot of the ln [LA-] to ln VO2 relationship. The methods used in this study provide a valid estimate of the LT and support the use of measured lowest VE/VO2 as an indirect measure of the LT. PMID- 8345315 TI - Metaphysics, rationality and science. AB - The debate over the metaphysical elements of Palmer's theories, and in chiropractic generally, has been a long and frequently bitter one. This article attempts to show the illogicality of both sides of the debate by reviewing the role of metaphysics in science and the discussions of metaphysics in philosophy. Within philosophy, metaphysics have been viewed, at least by those who do not object to them outright, as heuristic devices, which, although they cannot be subjected to either confirmation or refutation (that is, we cannot know if they are true or false), can be subjected to rational criticism. Furthermore, the article suggests that a critical confrontation with Palmer's metaphysical constructs should begin with a critique of vitalism, the philosophical source of these constructs (innate and universal intelligence). PMID- 8345316 TI - The effect of coffee consumption on serum cholesterol levels. AB - OBJECTIVE: Studies investigating the association of coffee consumption and serum cholesterol levels report conflicting results. In an attempt to resolve this controversy, we reviewed the literature to answer the question: Is there a true positive association between coffee consumption and serum cholesterol levels? DATA SOURCES: A Medline database search dating back to 1965 was utilized. Key words used in the search were coffee, caffeine and cholesterol. Cholesterol was expanded to include lipoproteins and LDL-, HDL- and VLDL-cholesterol. All articles that presented cholesterol data in association with coffee consumption were examined for references missed by Medline. Recently published articles were located by a hand search through Current Contents and the latest monthly editions of Index Medicus. STUDY SELECTION: Three reviewers made the decision to include all publications that met the following criteria: a) reported original experimental results; b) reported total serum cholesterol levels; and c) were published in peer-reviewed journals. DATA EXTRACTION: Two to four articles were read and analyzed each week in chronological order. Independent data extraction was performed by three reviewers, who then met as a group once a week to cross check the analyses. DATA SYNTHESIS: A trend, representing the association between coffee consumption and serum cholesterol, was calculated for each study. The trend was based on the percent difference in cholesterol values between subjects drinking four or more cups of coffee per day in comparison to those drinking zero or less than one cup of coffee each day. In order to compare studies that reported different cup sizes and different levels of intake, weighted mean cholesterol levels were calculated. In studies discussing the data in terms of correlations, trends were established according to the r values provided by the authors. CONCLUSIONS: The majority of studies demonstrated a positive trend in at least one subpopulation of their subjects, indicating that serum cholesterol levels increase with increasing coffee consumption. Stronger trends were seen among subjects drinking boiled coffee than in those drinking filtered, decaffeinated or instant coffee. However, most studies were not randomized clinical trials, and results can be countered by a number of biases prevalent in the studies, indicating the need for additional well-designed investigations to resolve remaining issues. PMID- 8345317 TI - Post-traumatic myelopathy following flopping high jump: a pilot case of spinal manipulation. AB - OBJECTIVE: To present the first case of spinal cord injury from high jump and the first pilot case of spinal manipulation for post-traumatic myelopathy. CLINICAL FEATURES: An 11-yr-old tetraplegic boy was admitted to the hospital, where he had a thorough neurological examination, including myelogram, EEG and skull and spinal X rays, with normal findings. The author revealed subtle subluxations on plain X-ray films. Triceps hyperreflexia was detected bilaterally. Bilateral patella and ankle clonus with hyperreflexia, basic and excess spasticity, and bilateral extensor plantar responses were noted in the lower limbs. A clinical diagnosis of early post-traumatic incomplete spastic tetraplegia below C7 was made. INTERVENTION AND OUTCOME: He did not respond to 3 months of orthodox conservative hospital management, including steroid therapy. Spinal manipulation of the lower cervical and upper thoracic spine was performed in a private chiropractic clinic for 2 wk. He apparently recovered after 3 months of spinal manipulation. On recent examination, he has virtually completely recovered. He still suffers from hand muscle atrophy, hyperreflexia of the triceps and ankle reflex and bilateral positive Babinski reflex; ankle and patellar clonus are almost absent. CONCLUSIONS: The early response and long-term (9-yr follow-up) benefits of spinal manipulation to the early delayed traumatic myelopathy of this patient suggest spinal cord ischemia as its pathophysiology. Mechanisms of post traumatic myelopathy are postulated. Biomechanical mechanisms of spinal manipulation for neurological recovery of post-traumatic myelopathy and/or radiculopathy are advanced. Further pilot spinal manipulation by experienced chiropractors after adequate anti-edematous (steroid) therapy is recommended for selected patients with post-traumatic myelopathy and/or radiculopathy, especially in a multidisciplinary spinal injury unit. PMID- 8345318 TI - Distraction manipulation reduction of an L5-S1 disk herniation. AB - OBJECTIVE: A computed tomography (CT)-confirmed L5-S1 disk protrusion is reported to be reduced following chiropractic adjustment, as seen on repeat CT scanning. Correlation of the CT reports with the patient's symptoms before and after manipulation is reported. CLINICAL FEATURES: A 38-yr-old female was treated for low back pain and right lower extremity first sacral dermatome sciatica. CT confirmed disk herniations at both the L4-L5 and L5-S1 levels were found. Motor weakness of the right gluteus maximus muscle was found and extremely tight hamstring muscles accompanying positive straight leg signs were elicited. A clinical and imaging diagnosis of an L5-S1 disk herniation was made. INTERVENTION AND OUTCOME: Distraction type chiropractic manipulation, electrical stimulation, exercises, nutrition advice and low back wellness class were administered with complete relief of sciatic pain and nearly complete relief of low back pain. CONCLUSIONS: Chiropractic distraction manipulation is an effective treatment of lumbar disk herniation, if the chiropractor is observant during its administration for patient tolerance to manipulation under distraction and any signs of neurological deficit demanding other types of care. PMID- 8345319 TI - Treatment of facial muscles affected by Bell's palsy with high-voltage electrical muscle stimulation. AB - OBJECTIVE: This report discusses high-voltage electrical muscle stimulation and chiropractic manipulation used to treat two patients who suffered from Bell's palsy. CLINICAL FEATURES: Case A: A 15-yr-old with left sided facial palsy was seen 2 days after the onset of symptoms. Upon observation, the left upper and lower eyelids were drooping and the left eye had excessive tearing. Motion palpation indicated multiple fixations in the cervical spine. Laboratory studies showed a microcytic anemia. A clinical diagnosis of Bell's palsy (House-Brackmann Grade V) and microcytic anemia was made. Case B: A 17-yr-old with left sided facial palsy was seen 8 days after onset of symptoms. Upon observation, the patient showed left sided facial paralysis and an inability to close the left eye completely. Motion palpation indicated multiple fixations in the cervical spine. A clinical diagnosis of Bell's palsy (House-Brackmann Grade V) was made. INTERVENTION AND OUTCOME: Both patients were treated with high-voltage pulsed galvanic current at 80 peaks/sec with a 7-inch hand-held held probe for 10 min each visit. In addition, the cervical spine fixations were mobilized using chiropractic manipulation. Case A was resolved after 6 wk of treatment and case B was resolved after 3 wk of treatment. CONCLUSION: Both patients benefited from these procedures with complete resolution of symptoms. The techniques outlined should be used at an early stage to accelerate progress toward normal facial muscle function. PMID- 8345320 TI - Intersegmental sagittal motion in the lower cervical spine and discogenic spondylosis: a preliminary study. PMID- 8345321 TI - Basilar artery migraine or cerebral vascular accident? PMID- 8345322 TI - Implicit memory: effects of network size and interconnectivity on cued recall. AB - Previous findings have indicated that the recall of a recently studied word is affected by how many associates it has in long-term memory (set size). The purpose of these experiments was to determine whether recall is also affected by the connectivity of these associates. Studied words were preselected to represent combinations of set size and connectivity and, in different experiments, recall was cued with extralist or intralist cues and with cues sharing few or many associates with the studied words. Effects of study time, encoding context, and levels of processing were also investigated. The results indicated that recall was more likely for words with smaller associative sets and for words with more interconnected sets of associates. These findings demonstrate that the recall of a recently presented word in the presence of a retrieval cue is affected by both the size and organization of its implicitly activated associative structure. PMID- 8345323 TI - Direct comparison of four implicit memory tests. AB - Four verbal implicit memory tests, word identification, word stem completion, word fragment completion, and anagram solution, were directly compared in one experiment and were contrasted with free recall. On all implicit tests, priming was greatest from prior visual presentation of words, less (but significant) from auditory presentation, and least from pictorial presentations. Typefont did not affect priming. In free recall, pictures were recalled better than words. The four implicit tests all largely index perceptual (lexical) operations in recognizing words, or visual word form representations. PMID- 8345324 TI - Implicit learning of color-word associations using a Stroop paradigm. AB - Our experiments asked whether implicit learning occurs for novel nonverbal associations. We presented subjects with color names printed in incongruent colors; subjects were asked to name the color in which the word was printed. In Experiment 1, each of 7 color words were associated with the same incongruent color across 6 blocks of trials, and then the color-word associations were abruptly changed. Both control subjects and patients with amnesia reduced their color-naming times across the first 6 trial blocks, and naming times increased when the color-word associations were changed. In Experiment 2, similar results were obtained when neutral words were associated with colors. In Experiment 3, we found that naming times were not disrupted when an irrelevant dimension (typecase) was changed. Finally, in Experiment 4, we found that the effect persisted across a 5-min delay. These studies provide evidence that implicit learning occurs for nonverbal associations and is independent of the brain structures damaged in amnesia. PMID- 8345325 TI - An evaluation of the total similarity principle: effects of similarity on frequency judgments. AB - Memory models that embody the total similarity principle (e.g., Gillund & Shiffrin, 1984; Hintzman, 1988; Murdock, 1982; Ratcliff, 1990) assume that frequency judgments reflect the total similarity of a test item to stimuli that have been studied. In 4 experiments, subjects estimated the frequencies of target words that had been presented in the context of varying numbers of semantically similar words. In a fifth experiment, subjects made forced-choice relative frequency judgments. The results of these experiments supported 1 prediction of total similarity models: Presenting similar words will increase rather than decrease frequency judgments of target words. However, a second prediction of these models was not supported. In particular, similar-word presentations had no effect on the judged frequencies of target words that had not been shown. PMID- 8345326 TI - Visual word recognition: a multistage activation model. AB - Although many models of word recognition have postulated loci for the simple effects of Context, Stimulus Quality, and Word Frequency, most of them are problematic in that they do not account for the pattern of joint effects among these factors. The experiments reported here show that, among other things, Word Frequency interacts with Context but is additive with Stimulus Quality in the context of a lexical decision experiment that also produces an interaction between Stimulus Quality and Context. The pattern of joint effects among these factors is accommodated by a multistage activation model that is based on the framework proposed by Besner and Smith (1992a). PMID- 8345327 TI - The cue-familiarity heuristic in metacognition. AB - Four experiments contrasted the cue-familiarity hypothesis of feeling-of-knowing judgments (FKJs) and tip-of-the-tongue feelings (TOTs) to the target retrievability hypothesis. Familiarity of the cues was contrasted to memorability of the targets in a paired-associate design (e.g., A-B A-B, A-B A-B', A-B A-D, A B C-D), in which the number of repetitions of the cue A terms was dissociated from the memorability of the target B terms. Little support was found for the target-retrievability hypothesis, because in none of the 4 experiments were FKJs related to target memorability. In one experiment, an omnibus retrieval hypothesis (which implicates total retrieval rather than just correct retrieval) and the cue-familiarity hypothesis produced isomorphic predictions that were borne out by the FKJ and TOT results. All 4 experiments supported the cue familiarity hypothesis, because FKJs and TOTs were directly related to the number of presentations (and thereby the familiarity) of the cues. PMID- 8345328 TI - Memory prerequisites of mismatch negativity in the auditory event-related potential (ERP). AB - The mismatch negativity (MMN) is a component of the auditory event-related brain potential that occurs in response to infrequent changes in the physical properties of homogeneous series of sounds, even when subjects are instructed to ignore the auditory channel of stimulation. It has been proposed (e.g., Naatanen, 1990) that the MMN is generated by an automatic process in which a difference between the deviant sound and the previous, standard sound is detected by the brain. However, it is unclear how the form of memory involved is related to the rest of the memory system. The present study indicates that, for an MMN to be elicited in response to a change in tone frequency, the representation of the standard tone must be both (a) well-established as a standard in memory, and (b) in a currently active state. The relation between physiological and psychological aspects of memory representation is discussed. PMID- 8345329 TI - Do the same stimulus-response relations influence choice reactions initially and after practice? AB - A two-choice reaction task was used to evaluate changes in stimulus-response translation with practice. In Experiment 1, four groups of Ss practiced with either a direct or indirect mapping of left-right stimuli to left-right responses and either a crossed or uncrossed hand placement and transferred to one of the four Mapping x Placement conditions. Stimulus-response location and response location-effector relations affected performance initially and after practice. In Experiments 2 and 3, Ss switched every 42 trials between conditions for which only the stimulus location-effector (Experiment 2) or stimulus-response location relation (Experiment 3) remained constant. Switching produced interference in Experiment 2 but not in Experiment 3, corroborating the influence of the stimulus response location relation on performance. Mediation based on spatial codes continues to be a factor in the performance of practiced Ss. PMID- 8345330 TI - Use of analogy in learning scientific concepts. AB - Four experiments compared learning of scientific concepts as expressed in either traditional literal form or through an analogy. Comprehension of basic-level details and inferential implications was measured through multiple-choice testing. In Experiment 1, literal or analogical renditions were presented in textual form only. In Experiment 2, text was accompanied by a dynamic video. In Experiment 3, the video and text literal rendition was compared with a text-only analogical rendition. In Experiment 4, subjects read only about a familiar domain. Subjects consistently answered basic-level questions most accurately when concepts were expressed literally, but answered inferential questions most accurately when concepts were expressed analogically. Analysis of individual differences (Experiment 2) indicated that this interaction strongly characterized the conceptual learning of science novices. The results are discussed within the framework of schema induction. PMID- 8345331 TI - Psychiatry in 2001. PMID- 8345333 TI - Practice guidelines: promise or panacea? PMID- 8345332 TI - Myocardial infarction. PMID- 8345334 TI - Interspecialty wars over endoscopy. PMID- 8345335 TI - The effect of parental expectations on treatment of children with a cough: a report from ASPN. AB - BACKGROUND: A previous retrospective study of children with cough raised questions about how physicians diagnose acute bronchitis. We hypothesized that if the physician perceives a parental expectation that an antibiotic is needed, it is more likely that a child with a cough will be diagnosed as having bronchitis and treated with an antibiotic. METHODS: Data were collected prospectively in 44 primary care practices in the Ambulatory Sentinel Practice Network. Variables examined included elements of the patient's history and physical examination, diagnoses made, and treatments prescribed. RESULTS: Data regarding 1398 patients were collected. A parental expectation that a prescription for an antibiotic would be given was associated with an increased likelihood of a diagnosis of bronchitis (relative risk 2.04, 95% confidence limits, 1.76 to 2.35, P < .001), and was second only to the physical finding of rales in the magnitude of its association with that diagnosis. The only other diagnosis associated with parental expectation of an antibiotic was viral upper respiratory tract infection, where parental expectation of treatment with an antibiotic was associated with a 49% reduction in the probability of that diagnosis. CONCLUSIONS: The expectations of parents of children with a cough appear to influence physician decision making. PMID- 8345336 TI - Extraordinary daytime urinary frequency in children. AB - BACKGROUND: Sudden onset of daytime urinary frequency of a small amount of urine in a previously toilet-trained child can be a disturbing problem. Psychosocial problems, problems at school, or problems within the family have to be taken into consideration. METHODS: Fifteen children with sudden onset of isolated daytime urinary frequency were evaluated and followed for a period of 12 to 18 months. A thorough medical and family history was obtained for each child, with special attention given to any psychosocial problems the child had experienced. All the children underwent a physical examination, complete urinalysis, and ultrasonography of the kidneys and bladder. RESULTS: In all of the patients, the urinalysis and ultrasonographic findings were within normal limits. A trigger factor was identified as the cause of urinary frequency in each case. CONCLUSIONS: Because urinary frequency is usually a benign self-limited condition, an extensive urological evaluation is not indicated. In most cases, providing reassurance to the parents and the child is the only intervention necessary. PMID- 8345337 TI - Physicians' usefulness ratings of family-oriented clinical tools. AB - BACKGROUND: Family-oriented patient care is a cornerstone of family practice. Family practice educators have proposed various methods to help the physician to better assess and treat families. Little is known, however, of the usefulness of family-oriented clinical tools to practicing physicians. METHODS: On a mailed survey questionnaire, 595 members of the Wisconsin Academy of Family Physicians were asked to rate the usefulness of 10 family-oriented tools and indicate the frequency of use and level of training received for each item. In addition, physicians rated their current and desired level of competency for involving families in patient care. RESULTS: Two hundred ninety-nine (50%) physicians responded. Most of the tools were rated as useful but used infrequently. Identifying the effects of chemical dependency on the health of families and conducting family conferences were rated as highly useful and frequently used skills. Clinical tools rated as least useful were record keeping by family charts and folders and family function assessment by the Family APGAR: Physicians who had received training in the use of a tool rated it as more useful, except for the Family APGAR and family charts or folders. Physicians with busier practices rated some of the tools as less useful than did other physicians. Respondents indicated a desire to develop their family counseling skills. CONCLUSIONS: Most family-oriented tools were reported to be useful but used infrequently by practicing physicians. Residency programs should continue to provide training for assessing and treating families, particularly in the areas of family systems theory, self-awareness of the physician's own family background, and the effect of chemical dependency on families. Future research should target larger and more varied groups of family physicians. PMID- 8345338 TI - Family practice and internal medicine office fees: an analysis of charge differences. AB - BACKGROUND: This study applies the concept of economic efficiency to primary health care physicians. Comparisons of charges made by family physicians and general internists would provide evidence of "optimal" health care delivery of primary care services. METHODS: A list of all active licensed primary care physicians was obtained from the office of the Oregon State Board of Medical Examiners. Two thousand eight hundred forty-three questionnaires were sent to Oregon primary care physicians. Of the 1365 responses, 484 were family physicians and 341 were general internists. RESULTS: The study found that family physicians had significantly lower mean office visit fees than general internists, while both groups had essentially similar patient mixes. This difference in fees could not be explained by patient case mix. CONCLUSIONS: The findings of this study and the body of literature available support the concept that family practice physicians provide economically efficient primary health care. If two similarly trained physicians provide a comparable level of medical care, with the same or similar outcome (or output), the physician who provides the care for the lowest cost should be used. PMID- 8345339 TI - Factors associated with research efforts of academic family physicians. AB - BACKGROUND: Family medicine has struggled to gain stature among academic medical disciplines. One factor has been the paucity of quality family medicine research. METHODS: Two hundred eight full-time physician faculty members at family practice residency programs completed a survey that focused on demographics, training, experience, professional activities, and factors that motivated them to select academic careers. Bivariate and multivariate analyses were performed to determine if any of these factors was associated with increased time spent on research. RESULTS: Faculty members who spent 10% or more of their professional time on research were more likely to be fellowship trained, employed in university training programs, have more academic experience, and to cite the opportunity to do research as a factor motivating them to enter academic medicine. However, when multivariate analysis was performed, the only significant factor that predicted that a faculty member would devote 10% or more time to research was having an interest in research when first seeking a position in academic medicine. CONCLUSIONS: The amount of time that family medicine faculty members dedicate to research is related to a strong interest in research when seeking their academic position. Fellowship training and an academic environment may have assisted faculty in performing research, but were not independent predictors of future involvement in research. PMID- 8345340 TI - Screening for diabetic retinopathy in a clinical setting: a comparison of direct ophthalmoscopy by primary care physicians with fundus photography. AB - BACKGROUND: Type II diabetes mellitus is a major health problem among Native Americans, and diabetic retinopathy is a frequent complication of this disease. Screening for retinopathy can identify early disease and prevent major vision loss, but the most cost-effective screening method has not yet been determined. METHODS: In a rural clinic that served more than 400 Native Americans with diabetes, we compared the accuracy of referrals made based on two screening methods: ophthalmoscopy by trained primary care physicians and seven-view nonstereoscopic, mydriatic fundal photography read by two general ophthalmologists and a retinal specialist. Patients in whom abnormal findings were detected by either screening method were then referred to a general ophthalmologist for further evaluation. RESULTS: Two hundred forty-three examinations were performed and 83 referrals made. Both screening methods had high sensitivity for referring patients with retinopathy that required treatment or follow-up sooner than 1 year (100% for direct ophthalmoscopy by primary care physicians, 94% for the general ophthalmologist photography readers, and 100% for the retinal specialist reader). The calculated costs of screening by direct ophthalmoscopy and by retinal photography were 64% less and 44% to 35% less, respectively, than the cost of yearly ophthalmological examinations by ophthalmologists. CONCLUSIONS: Careful screening for treatable diabetic eye disease by trained primary care physicians proved to be a clinically acceptable, cost-effective strategy. Screening methods for diabetic retinopathy should be evaluated based on the absolute sensitivity, specificity, and predictive values of their ability to correctly refer patients rather than their diagnostic accuracy. PMID- 8345341 TI - A critique of the practice-expense values of the resource-based relative value scale. AB - The resource-based relative value scale (RBRVS) was implemented by the Health Care Financing Administration on January 1, 1992. The practice-expense payments from the old Medicare fee scale were moved unchanged into RBRVS. This resulted in underpayment of office-based practice expenses and overpayment of hospital-based practice expenses. For example, office visits are underpaid by $10.28, whereas coronary angiograms are overpaid by $123.00. Unpaid practice expenses reduce the after-expense physician-work fee of the average office visit by about one half, yet overpayment of practice expenses for some hospital procedures almost doubles the after-expense physician-work fee for some subspecialties. Inflation will likely increase the actual practice expense of the average office visit to the point that the after-expense physician-work fee for the family physician will be reduced to zero by the year 2001. PMID- 8345342 TI - Pathophysiology and management of endometriosis. AB - Endometriosis is a common disease that affects up to 5 million women in the United States. Specifically the prevalence of endometriosis is 1 in 15 (7%) women of reproductive age, and there is an associated incidence of infertility in as many as 30% to 40% of cases. The precise physiologic mechanism for the development of endometriosis lesions in the pelvis and abdominal cavity has not been elucidated. Substantial evidence exists, however, that endometriosis is dependent on estrogen for continued growth and proliferation. Therefore, suppression of the hypothalamic-pituitary-ovarian axis with analogues of a gonadotropin-releasing hormone is being increasingly undertaken. Since the most effective resolution of endometriosis occurs after oophorectomy or onset of menopause, the hypoestrogenic state induced by GnRH analogues is of major significance for patients with active disease. Medical therapy for endometriosis is often used as primary therapy for symptomatic disease or as an adjunct to surgical management of pelvic pain or infertility. PMID- 8345343 TI - Failure of insulin treatment in obese patients with non-insulin-dependent diabetes mellitus. AB - A number of experts recommend the use of insulin for patients with non-insulin dependent diabetes mellitus (NIDDM) who fail to respond to diet, exercise, and oral hypoglycemics, even when the patient is morbidly obese. This article describes the use of insulin in two obese patients with NIDDM whose obesity worsened following the institution of insulin therapy. In some cases the risk for increased obesity and its complications following the institution of insulin may offset the potential benefits of insulin therapy itself. There are two main drawbacks associated with insulin therapy in these patients. First, from a medical point of view, insulin has a lipogenic effect and may actually contribute to weight gain, hyperinsulinemia, and increased insulin resistance in obese patients with NIDDM. Second, from a behavioral point of view, the institution of insulin therapy may shift the patient's and physician's focus from the preferred lifestyle adjustments to the numerous details associated with insulin use and monitoring. Since weight gain and sedentary activity are themselves risk factors for coronary artery disease, the benefits of decreased blood glucose levels should be balanced against the risk of increased weight gain in these patients. PMID- 8345344 TI - Appendectomies for Madeline and Madlon. PMID- 8345345 TI - The closteroviruses, capilloviruses and other similar viruses: a short review. PMID- 8345346 TI - Involvement of cellular adhesion sequences in the attachment of adenovirus to the HeLa cell surface. AB - Immunofluorescence analysis of HeLa cells incubated with human adenovirus serotype 2 (Ad2) inoculum suggested that Ad2 receptors co-localized with the receptors of fibronectin (FNR) and vitronectin (VNR) at the cell surface. Ad2 adsorption also resulted in the occurrence of intracytoplasmic actin cables with submembranal anchorage. The cell binding of Ad2 virions, pentons and fibres was found to be efficiently inhibited by concanavalin A, laminin, anti-FNR and anti VNR antibodies. Arginine-glycine-aspartyl tripeptide (RGD) and other related peptides reproducing cellular attachment sequences of adhesion proteins also competed with Ad2 for cell adsorption, and drastically reduced the virus progeny yield at the end of the infectious cycle. Data from binding competition assays with Ad2 virions showed that the apparent affinity constants of RGD motif containing peptides for Ad2 receptor ranged from 0.75 x 10(8) M-1 to 2.2 x 10(8) M-1, with a number of peptide recognizing sites varying from 1.5 x 10(4) to 9 x 10(4) per cell for the different peptides studied. Polypeptide analysis of labelled plasma membrane fractions isolated after cross-linking to unlabelled Ad2 virions showed three major protein species with apparent M(r) of 130K, 60K and 44K, respectively, reacting with anti-FNR and anti-VNR antibodies. These results suggested that Ad2 and extracellular matrix proteins recognize similar adhesion sequences at the surface of HeLa cells, or alternatively that integrins and Ad2 receptors have overlapping ligand specificity. PMID- 8345347 TI - Restricted replication of respiratory syncytial virus in human alveolar macrophages. AB - The cellular factors that regulate infection and replication of respiratory syncytial virus (RSV) in human alveolar macrophages were examined. RSV-exposed alveolar macrophages demonstrated a time-dependent expression of viral glycoproteins, maximal by 24 h post-infection resulting in infection of approx. 38% of the cells. Essentially all (33%) of these freshly isolated alveolar macrophages replicated RSV as shown by infectious centre assays. This RSV permissive subpopulation of alveolar macrophages consisted primarily of major histocompatibility class II-expressing cells as determined by fluorescence activated cell sorting. Re-infection of alveolar macrophages did not significantly alter the number of cells infected or capable of replicating RSV. However, in vitro differentiation of alveolar macrophages prior to infection resulted in a significant (P < 0.05), time-dependent decrease (approx. sevenfold) in the number of cells that replicated virus. The mechanism by which cellular differentiation restricted RSV replication is unknown. Production of defective interfering particles did not account for this decrease. Alveolar macrophages infected with RSV produce a variety of cytokines potentially contributing to this restricted viral replication. Pretreatment with several of these cytokines did not affect viral infection or replication. However, tumour necrosis factor (TNF alpha) significantly (P < 0.05) decreased viral replication but only by 30 to 60%. Thus RSV replication is reduced by in vitro differentiation of alveolar macrophages and, to a lesser degree, by pretreatment with TNF. PMID- 8345348 TI - Morphological and genomic characterization of two reoviruses (P and W2) pathogenic for marine crustaceans; do they constitute a novel genus of the Reoviridae family? AB - P and W2 viruses are pathogenic in two crustaceans of the Mediterranean Sea, Macropipus depurator and Carcinus mediterraneus, respectively. Investigation of virus, virus density and genome structure leads us to propose their classification in a genus similar to aquareovirus of the Reoviridae family. They differ from aquareoviruses by the number of dsRNA segments forming the genome (12 instead of 11), their electrophoretic pattern in PAGE (1/5/6 instead of 3/3/5), and the absence of virus replication in fish cell lines. PMID- 8345349 TI - Identification of cellular proteins that bind to the human immunodeficiency virus type 1 nef gene product in vitro: a role for myristylation. AB - The human immunodeficiency virus (HIV) type 1 nef gene product was expressed as an N-terminal fusion protein with glutathione-S-transferase (GST) in the baculovirus system. The resulting nefGST fusion protein was found to be authentically myristylated at the N terminus and could be purified to homogeneity by one-step affinity chromatography on immobilized glutathione. The high affinity of nefGST for glutathione was exploited to develop an assay to identify cellular proteins capable of interacting with nef. Several such proteins were identified in extracts from the Jurkat human T cell line. The interaction between nef binding proteins and immobilized nefGST could be specifically competed by the addition of soluble nef. Cell fractionation showed that nef-binding proteins were present in both cytosolic and membrane-associated fractions. A non-myristylated derivative failed to bind to the membrane-associated proteins but was able to bind to the cytosolic group, albeit with reduced affinity. In addition, a single protein present in both soluble and membrane-associated fractions exhibited myristylation-independent binding to nef. By analogy with other myristylated proteins such as MARCKS (myristylated alanine-rich C kinase substrate) and the Rous sarcoma virus transforming protein, src, the membrane-associated proteins that bind only to myristylated nef may represent a specific membrane target for nef. The cytosolic proteins that interact with nef may constitute soluble components of an as yet unidentified signal transduction pathway which is the target of nef action in the HIV-1-infected cell. PMID- 8345350 TI - Characterization of an early gene coding for a highly basic 8.9K protein from the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus. AB - A new gene of the baculovirus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) has been identified that encodes a highly basic 8.9K protein. The gene called p8.9 is expressed as a 0.5 kb transcript by 1 h post infection and initiates at an early gene motif. The promoter of the 0.5 kb transcript has two upstream elements, repeats I and II, which are similar to motifs previously characterized in the OpMNPV IE-2 gene and the Autographa californica nuclear polyhedrosis virus IE-N and PE38 genes. A second p8.9 transcript expressed from 8 to 72 h post-infection was shown to initiate 634 bp upstream from the early gene motif in a region that has no similarity to any previously described baculovirus promoter or initiation site. Transient assays utilizing a reporter gene have shown that the p8.9 early promoter is active in a Lymantria dispar (LD652Y) and Spodoptera frugipeda (Sf9) cell lines in the absence of other viral factors. In addition, it was also demonstrated that the p8.9 promoter is trans-activated by the OpMNPV IE-2 and p34 genes, but not by IE 1. PMID- 8345351 TI - Replication of Cydia pomonella granulosis virus in cell cultures. AB - Several primary cell lines that support the complete replication of Cydia pomonella granulosis virus have been established from one culture of C. pomonella embryonic cells. Virus passaged three times in cells and once in larvae showed no change in restriction enzyme fragment patterns. Stages in virus replication observed by electron microscopy resembled those from in vivo studies. Cell lines that were maintained at or below 21 degrees C retained susceptibility to virus over a period of 4 years whereas the same cell lines maintained at 27 degrees C gradually lost their susceptibility and eventually could not be infected at all. PMID- 8345352 TI - A strong-stop DNA in rice plants infected with rice tungro bacilliform virus. AB - A virus-specific small nucleic acid (strong-stop DNA) was identified in rice plants infected with rice tungro bacilliform virus, but not in the virus particles. This nucleic acid was shown to consist of about 595 deoxyribonucleotides with about 70 ribonucleotides covalently linked at the 5' end. Hybridization with sequence-specific oligonucleotides showed that the ribonucleotides were from the plant cytoplasmic tRNA(iMet) sequence. PCR analysis detected hairpin structures at the 3' end of the DNA. PMID- 8345354 TI - Characterization of a single SA7-like VA RNA gene in subgroup F adenoviruses. AB - The virus-associated (VA) RNA gene regions of the human subgroup F adenoviruses (types 40 and 41) were amplified using primers corresponding to flanking open reading frames of human and simian (SA7) adenovirus sequences previously published. The subgroup F adeno-viruses, like human Ad12 (subgroup A) and SA7, were found to have only one VA RNA gene at this locus (map unit 30). The type 40 and type 41 VA RNA genes have primary sequence characteristics in common with other known VA RNA genes, have high cross-identity (93%), and show appreciably higher identity to the single VA RNA gene present in SA7 (77% and 81%, respectively) than to any of the VA RNA genes of Ad2, Ad7 or Ad12 (< 61%). These findings may have implications for explaining the evolution and growth peculiarities of human subgroup F adenoviruses. PMID- 8345353 TI - Nucleotide sequence of the Buzura suppressaria single nucleocapsid nuclear polyhedrosis virus polyhedrin gene. AB - A portion of the genome of the Buzura suppressaria (Lepidoptera) single nucleocapsid nuclear polyhedrosis virus (BsSNPV) containing the polyhedrin gene was sequenced. An open reading frame of 738 nucleotides encoded a protein of 246 amino acids and represented the polyhedrin gene. A conserved TAAG motif, associated with transcriptional start sites in other polyhedrin genes, was identified 51 nucleotides upstream of the BsSNPV polyhedrin gene. A putative polyadenylation signal, AATAAA, was found immediately downstream of the polypeptide termination codon. Comparison of the amino acid sequence of BsSNPV polyhedrin with other NPV polyhedrins and granulosis virus granulins showed that the BsSNPV polyhedrin was most closely related to the polyhedrin of Orgyia pseudotsugata (Lepidoptera) SNPV and most distantly related to the polyhedrin of Neodiprion sertifer (Hymenoptera) SNPV. PMID- 8345355 TI - Identification of a new hepatitis B virus (HBV) genotype from Brazil that expresses HBV surface antigen subtype adw4. AB - The complete genome of a hepatitis B virus (HBV) from Brazil that expressed the subtype adw4 of HBV surface antigen (HBsAg) was cloned and sequenced. The genome, termed w4B, consists of 3215 bp. The overall genetic organization of typical hepadnaviruses with four open reading frames including the preC region was found to be conserved. When comparing the w4B sequence with 19 complete HBV genomes it was, however, found to be more divergent (15%) than any other HBV sequence thus far reported. Until now, no more than 11% divergence has been reported. Distinct from the five known HBV genotypes A to E, w4B made up a new, sixth genotype. The importance of the conserved third start codon in the HBV X gene became apparent in isolate w4B. By mutation, this ATG was out of frame, and by what appears to have been a linked mutation, a new start site two codons downstream was re established. The significance of several other mutations is discussed. PMID- 8345357 TI - Location on the evolutionary trees of the non-structural protein (NS) and neuraminidase (NA) genes of late human influenza A (H2N2) viruses: parental viruses of the NS and NA genes of Hong Kong influenza A (H3N2) viruses. AB - The nucleotide sequences of the non-structural protein (NS) and neuraminidase (NA) genes of human influenza A (H2N2) viruses isolated in 1967 and 1968 in Europe, Asia and North and South America were located on evolutionary trees in order to identify the parental virus of Hong Kong influenza A (H3N2) viruses, which appeared in the human population in 1968. From the evolutionary trees, the H2N2 viruses isolated during the 1967 to 1968 period were divided into two groups. Group I includes that A/Tokyo/3/67, A/Hachioji/1/67, A/Perg/1/68, A/Cordoba/522/67, A/Texas/2/68 and A/Berkeley/1/68 viruses, whereas group II includes the A/Georgia/1/67, A/England/10/67 and A/Poland/6/67 viruses. The NS and NA genes of Hong Kong H3N2 viruses isolated in 1968 were genetically closer to those of group II viruses and closest to those of A/Poland/6/67. PMID- 8345356 TI - Lipopolysaccharide inhibits the production of lymphocytic choriomeningitis virus in a human monocytic cell line. AB - The human monocytic cell line THP-1 was used as a model to study the mechanism of infection in the monocyte/macrophage, a natural target of lymphocytic choriomeningitis virus (LCMV) infection in vivo. Both the virulent strain, LCMV.WE, and the avirulent strain, LCMV.ARM, infected THP-1 cells, but did not stimulate THP-1 cells to secrete interleukin 1 (IL-1) or tumour necrosis factor (TNF-alpha). When lipopolysaccharide (LPS) was added to THP-1 cells together with LCMV, an 80 to 90% reduction in the number of infected cells (measured by immunofluorescence) and a 90% reduction in viral plaques was observed 5 to 6 days post-infection. Neither interferon alpha (IFN-alpha) nor IFN-beta were detected in supernatants from THP-1 cells after the addition of LCMV, LPS, or LPS plus LCMV. In contrast, the same levels of IL-1 and TNF-alpha were observed in the presence of LPS and LCMV, or LPS alone. However, antibodies to IL-1, TNF-alpha, interleukin 6 and IFN-alpha did not block the antiviral effect of LPS. In kinetic studies, LPS added 1 day after adding LCMV to THP-1 cells was still effective in reducing the number of infected cells. Our findings suggest that LPS alters cellular metabolism, possibly through the induction of IFN-alpha, and that IFN alpha in the absence of LPS suppresses virus production. PMID- 8345358 TI - Production of the M2 protein of influenza A virus in insect cells is enhanced in the presence of amantadine. AB - Recombinant baculoviruses that express the M2 protein from the genes of either the amantadine-sensitive, influenza A/Ann Arbor/6/60 virus or a laboratory derived, amantadine-resistant mutant of this virus were constructed. Addition of amantadine or rimantadine at 2 micrograms/ml to cultures of Sf9 cells infected with the recombinant baculoviruses increased the yield of the M2 protein from the amantadine-sensitive virus approximately 10-fold, but did not increase the yield of the M2 protein from the amantadine-resistant virus. Flow cytometry demonstrated that the increased production of M2 in the presence of amantadine resulted in increased cell surface expression of the M2 protein. Pulse-chase experiments indicated that whereas the rate of synthesis of the M2 protein increased in the presence of amantadine, the M2 protein was stable in both the presence and absence of amantadine. Addition of amantadine to Sf9 cells as late as 72 h after infection with the recombinant virus increased the production of M2 protein. These data suggest that the M2 protein exerts some biological activity in Sf9 cells. PMID- 8345359 TI - Characterization of the gene encoding the A-type inclusion protein of camelpox virus and sequence comparison with other orthopoxviruses. AB - A gene was identified in camelpox virus strain CP-1 that is similar to the 160K gene of cowpox virus strain Brighton (BR) that encodes the A-type inclusion body protein (ATIP). The CP-1 gene was mapped, sequenced, and the presence of the ATIP specific mRNA was demonstrated. The open reading frame [2178 nucleotides (nt)] was found at a similar position in the CP genome as the one reported for the cowpox virus 160K ATI gene. DNA sequence comparison revealed a deletion of two adjacent adenine residues relative to cowpox virus BR, generating a reading frame shift accompanied by the formation of a translational stop codon. An identical deletion has been described for vaccinia virus strain Western Reserve. The DNA sequence of the corresponding region of monkeypox virus strain Copenhagen revealed a deletion leading to a putative stop codon 75 nt upstream of the same stop codons in the camelpox and vaccinia virus genes. These findings are consistent with the expression of truncated ATIPs, of 94K in vaccinia and camelpox viruses and of 92K in monkeypox virus. In addition, a deletion of 789 bp could be localized downstream of the ATI open reading frame in camelpox virus isolates of different origin. This causes the transcription of a shortened ATI specific mRNA (3.7 kb) relative to vaccinia and cowpox viruses (both 4.5 kb). The similarity observed in ATIP-encoding and flanking sequences might suggest that vaccinia and camelpox viruses are descended from a common ancestor. PMID- 8345360 TI - Sindbis virus pathogenesis: phenotypic reversion of an attenuated strain to virulence by second-site intragenic suppressor mutations. AB - Monoclonal antibodies (MAbs) specific for the E2c neutralizing antigenic site on the Sindbis virus E2 glycoprotein define a pathogenesis domain that affects neonatal mouse virulence. Sequence analysis of E2c MAb escape mutants showed that the domain included E2 amino acids 62, 96 and 159. The pathogenesis domain is also influenced by changes at E2 position 114. Mutation of E2 residues Asn 62 to Asp or Lys 159 to Glu results in suppression of the attenuated phenotype conferred by a mutation from Ser to Arg at E2 position 114. Possible mechanisms of phenotypic suppression within the E2c pathogenesis domain were investigated by using site-directed mutagenesis to determine the effects of specific combinations of positively charged, negatively charged and uncharged amino acid substitutions at E2 positions 62, 114 and 159. Phenotypic reversion to virulence by second-site suppressor mutations at E2 amino acids 62 or 159 was not dependent on ionic interaction with the residue at E2 114. Rather, suppression appeared to be the result of independent virulence effects mediated by specific residues. PMID- 8345361 TI - Subgenomic RNAs of Lelystad virus contain a conserved leader-body junction sequence. AB - During the replication of Lelystad virus in alveolar lung macrophages, a 3' coterminal nested set of six subgenomic RNAs (RNA2 to RNA7) is formed. These contain a common leader sequence derived from the 5' non-coding region of the genomic RNA. In this study, the sequence of the junction sites, i.e. the sites where the leader sequence joins to the body of the subgenomic RNA, was determined for all six subgenomic RNAs. For each subgenomic RNA, six to nine cDNA clones were isolated by means of reverse transcription and PCR. The nucleotide sequence at the junction site was identical for all eight cDNA clones derived from subgenomic RNA4. However, heterogeneity was observed in the nucleotide sequence surrounding the junction sites of the cDNA clones derived from subgenomic RNAs 2, 3, 5, 6 and 7. This heterogeneity suggests that the fusion of the leader to the body of the subgenomic RNA may be imprecise. The junction sites of the six subgenomic RNAs had a conserved sequence motif of six nucleotides (UCAACC or a highly similar sequence). The distance between the junction site and the translation initiation codon of the downstream open reading frame varied from nine to 83 nucleotides. PMID- 8345362 TI - St Louis encephalitis virus establishes a productive, cytopathic and persistent infection of Sf9 cells. AB - The Sf9 cell line, commonly used for gene expression by recombinant baculovirus, has been productively infected by St Louis encephalitis (SLE) virus, a flavivirus. SLE viral infection produced a c.p.e. in the Sf9 cells characterized by giant cells and the presence of 10-fold fewer cells in the infected cultures after the first week of infection compared with uninoculated control cultures. Infected Sf9 cells expressed SLE viral antigens, and intracellular virus particles were observed by electron microscopy. Titres of cell-associated SLE virus rose slightly over an 8 week period, whereas titres of cell-free virus remained stable, suggesting that SLE virus establishes a productive and persistent infection of Sf9 cells. The SLE virus produced by the Sf9 cells could be neutralized by SLE virus-immune mouse ascitic fluid, and no evidence of escape mutants was detected. Sf9 cells persistently infected with SLE virus could be superinfected with a recombinant baculovirus and expressed recombinant antigen. The successful infection of Sf9 cells by SLE virus represents the first report of production of c.p.e. by SLE virus in insect cells under routine cell culture conditions and of the infection of Sf9 cells by a human pathogen. PMID- 8345363 TI - Sequence and structure of defective interfering RNAs associated with cucumber necrosis virus infections. AB - The presence of symptom-attenuating defective interfering (DI) RNAs in a laboratory culture of cucumber necrosis tombusvirus (CNV) was confirmed. Sequencing of cDNA clones of these DI RNAs revealed that CNV DI RNAs retained sequences from the CNV 5'-untranslated and 3'-terminal regions as well as a portion of the coding region for the 92K protein. Similar sequence arrangements were also observed in symptom-attenuating DI RNAs generated de novo from synthetic wild-type CNV transcripts. A comparison of the sequences and biological activities of these CNV DI RNAs is presented. In co-infections of synthetic wild type CNV and CNV DI RNAs, prominent RNA species of a higher M(r) than the DI RNA used in the co-infection were found. The possible nature of these RNA species is discussed. PMID- 8345364 TI - The involvement of cowpea mosaic virus M RNA-encoded proteins in tubule formation. AB - On the surface of cowpea protoplasts inoculated with cowpea mosaic virus (CPMV), tubular structures containing virus particles have been found. Such tubular structures are thought to be involved in cell-to-cell movement of CPMV in cowpea plants. To study the involvement of the 58K/48K and capsid proteins of CPMV in the formation of the tubular structures, mutations were introduced into M cDNA clones from which infectious transcripts could be derived. No tubules were found on protoplasts inoculated with a mutant that fails to produce the 48K protein nor with a mutant that has a deletion in the 48K coding region, suggesting that the 48K protein is essential for this process. However, a possible role of the 58K protein in tubule formation could not be excluded. A mutant that fails to produce the capsid proteins did produce tubules and therefore the capsid proteins are not involved in the formation of the tubular structures. Electron microscopic analysis revealed that the tubules produced by this mutant are, apart from the absence of virus particles, morphologically identical to the tubules formed by the wild-type virus. PMID- 8345365 TI - Immunocytochemistry of B-50 (GAP-43) in the spinal cord and in dorsal root ganglia of the adult cat. AB - The distribution of the neural-specific growth associated protein B-50 (GAP-43), which persists in the mature spinal cord and dorsal root ganglia, has been studied by light and electron microscopic immunohistochemistry in the cat. Throughout the spinal cord, B-50 immunoreactivity was seen confined to the neuropil, whereas neuronal cell bodies were unreactive. The most conspicuous immunostaining was observed in the dorsal horn, where it gradually decreased from superficial laminae (I-II) toward more ventral laminae (III-V), and in the central portion of the intermediate gray (mainly lamina X). In these regions, the labelling was localized within unmyelinated, small diameter nerve fibres and axon terminals. In the rest of the intermediate zone (laminae VI-VIII), B-50 immunoreactivity was virtually absent. The intermediolateral nucleus in the thoracic and cranial lumbar cord showed a circumscribed intense B-50 immunoreactivity brought about by the labelling of many axon terminals on preganglionic sympathetic neurons. In motor nuclei of the ventral horn (lamina IX), low levels of B-50 immunoreactivity were present in a few axon terminals on dendritic and somal profiles of motoneurons. In dorsal root ganglia, B-50 immunoreactivity was mainly localized in the cell bodies of small and medium sized sensory neurons. The selective distribution of persisting B-50 immunoreactivity in the mature cat throughout sensory, motor, and autonomic areas of the spinal cord and in dorsal root ganglia suggests that B-50-positive systems retain in adult life the capacity for structural and functional plasticity. PMID- 8345366 TI - Distribution of three retinal proteins in developing octopus photoreceptors. AB - The expression of proteins unique to plasma membrane domains of developing photoreceptors is used as a marker for retinal differentiation in vertebrates. Invertebrate photoreceptors are also compartmentalized, but little information is available on the development of these compartments or the expression of retinal proteins specific to these cellular regions. Using routine electron microscopy techniques, we have made observations on the formation of photoreceptor organelles, including myeloid bodies and rhabdomeres, in embryonic octopus eyes from an early stage in development through hatching. Immunocytochemical experiments on the embryos demonstrate a timed expression of three retinal proteins during development, and the early separation of the octopus photoreceptor plasma membrane into distinct domains. Using polyclonal antibodies for opsin, retinochrome and retinal binding protein we have shown that opsin appears first and is confined to the distal end of the photoreceptor that will eventually differentiate into rhabdomeres. This membrane domain is separated from the proximal/inner segment plasma membrane by a septate junction. Retinochrome is expressed later when the myeloid bodies appear in the inner segments, and retinal binding protein is apparently not synthesized until sometime after hatching. These results suggest that, in the cephalopod retina, protein components of the retinoid cycling apparatus appear in a specific developmental sequence during the differentiation of this tissue. PMID- 8345367 TI - Observations on the progress of Wallerian degeneration in transected peripheral nerves of C57BL/Wld mice in the presence of recruited macrophages. AB - The first part of this study is a description of the effect of the intraneural injection of lysophosphatidyl choline into the sciatic nerves of C57BL/Wld mice. This mouse is unusual because its peripheral nerve fibres degenerate very slowly after transection, and few myelomonocytic cells are recruited into the endoneurium after traumatic injury. However, intraneural injection of lysophosphatidyl choline produced a typical demyelinating lesion in which recruited macrophages were active in removal of myelin. In the second part of the study, nerves were transected either before, at the same time as, or some days after, the intraneural injection of lysophosphatidyl choline into the distal stump; the changes within the endoneurium were compared with those seen in distal stumps which had not been injected with lysophosphatidyl choline. Immunohistochemical and ultrastructural examination during the period 1-4 weeks after transection showed that degeneration occurred in the portion of each nerve which had been injected with LPC (and which therefore contained exogenous macrophages) but failed to occur in the portion of nerve which was not penetrated by the injected bolus of lysophosphatidyl choline. It is suggested that the unusual property of sealing off of the tips of the transected axons within the distal stumps may be a significant factor in maintaining 'normal' Schwann cell axon relationships along transected axons, even though the axons are separated from their cell bodies. Lysophosphatidyl choline destabilises the Schwann cell axon relationship by initiating myelin breakdown within the Schwann cell. It is suggested that while the Schwann cells remain closely associated with the axons in the distal stumps, they do not behave as denervated cells and consequently may be incapable of signalling their damaged status. PMID- 8345368 TI - Near-infrared monitoring of the cerebral circulation. AB - Near-infrared spectroscopy is a noninvasive bedside technique for monitoring hemoglobin saturation (HbO2%) in brain vasculature. The method linearly relates the optical signal detected from the surface of the head to HbO2%. To do so, the method relies on constant transcranial optical pathlength and light scattering as well as minimal interference by tissues overlying the brain. This study examined these premises. Optical signals from a dual-wavelength, near-infrared spectrometer were correlated with sagittal sinus HbO2% in 7 anesthetized piglets subjected to 7 different physiological conditions: normoxia, moderate and severe hypoxia, hyperoxia, hypocapnia, hypercapnic hyperoxia, and hypotension. These conditions were induced by varying the inspired O2 concentration (7-100%), ventilatory rate (5-35 breaths/min), and blood pressure (phlebotomy 20 ml/kg) to force HbO2% over a wide range (5-93%). To evaluate interference by tissues overlying the brain, correlations were repeated after the scalp and skull were rendered ischemic. Transcranial optical pathlength was measured by phase modulated spectroscopy. Linear relationships between optical signals and sagittal sinus HbO2% were found with correlation coefficients ranging from -0.89 to -0.99 (p < 0.05) among animals; however, slope and intercept had coefficients of variability of approximately 15 and 333%, respectively. Almost identical linear expressions were observed whether scalp and skull were ischemic or perfused. Transcranial optical pathlength was constant in each animal, but ranged from 10 to 18 cm among animals. The data indicate that the assumptions underlying near infrared spectroscopy are reasonably accurate in a given animal, but that the constants for transcranial optical pathlength and light scattering are not the same in all animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345369 TI - Clinical experience with a fiberoptic intracranial pressure monitor. AB - Retrospective clinical experience with our first 46 patients monitored with a fiberoptic intracranial pressure device is described. In 43 of 46 patients, the transducer was introduced into brain parenchyma. A ventriculostomy system was used in 3 of 46 patients. The monitoring system was generally characterized by ease of placement and system maintenance and by technical simplicity. Several problems were encountered, including breakage of system components (12%), erroneous readings requiring transducer repositioning (8.6%), epidural hematoma (3.4%), and infection (1.7%). No infections or hematomas occurred in the 3 cases in which the ventriculostomy system was used. Overall, our experience with the Camino intracranial pressure fiberoptic monitoring system confirms previous reports of its favorable features. PMID- 8345370 TI - Electroencephalogram spectral edge frequency, lower esophageal contractility, and autonomic responsiveness during general anesthesia. AB - Both the electroencephalogram (EEG) spectral edge frequency (SEF) and lower esophageal contractility (LEC) indices have been reported to be useful indicators of anesthetic depth. We designed a prospective study to evaluate the relationship between changes in these two variables and objective measurements of physiologic responsiveness to surgical stress (i.e., changes in hemodynamic variables and plasma levels of norepinephrine, epinephrine, total catecholamines, and vasopressin). Eighty-nine consenting adult males undergoing radical prostatectomy procedures under a standardized general anesthetic technique were studied according to a randomized, single-blinded protocol. General anesthesia was induced with 30 micrograms/kg intravenous (i.v.) alfentanil, 2.5 mg/kg i.v. thiopental, and 0.1 mg/kg i.v. vecuronium, and subsequently maintained with 0.5 microgram/kg/min alfentanil, nitrous oxide (N2O) 67% in oxygen, and 0.8 microgram/kg/min vecuronium. Following retropubic dissection, 81 patients (92%) manifested acute hypertensive responses, with mean arterial pressure increasing from 90 +/- 14 to 122 +/- 14 mm Hg (mean +/- SD). This acute hypertensive response was treated with one of three different treatment modalities (20 to 60 micrograms/kg i.v. alfentanil, 0.5 to 2.0% inspired isoflurane, or 0.05 to 0.15 mg/kg i.v. trimethaphan) to return the mean arterial pressure to within 10% of the preincisional (baseline) value within 5 to 10 minutes. Although the mean arterial pressure, heart rate, and plasma levels of catecholamines and vasopressin significantly increased following the surgical stimulus, and decreased after adjunctive therapy, the EEG-SEF and LEC index (LECI) values did not significantly change during these study intervals. Furthermore, using a logistic regression analysis, we observed that preincision EEG-SEF and LECI values could not predict whether patients would manifest a hypertensive response. Therefore, the EEG-SEF and LECI were unreliable indicators of anesthetic depth. PMID- 8345371 TI - Spinal evoked potential in patients undergoing thoracoabdominal aortic reconstruction: a prognostic indicator of postoperative motor deficit. AB - We studied 76 patients who had thoracoabdominal aortic reconstruction between January 1981 and March 1991. Evoked potential monitoring of the spinal cord (peridural bipolar catheter stimulation at level L4-L5, recording via a second bipolar catheter at level Th4) was used to predict intraoperatively a possible motor deficit. There was a close linear correlation of r = 0.892 between postoperative motor deficit (normal, paraparesis, paraplegia) and the time from declamping to reappearance of the potential. Forty-three of 76 patients received prostaglandin E1 (5 ng/kg/min) for pharmacologic protection of the spinal cord 15 minutes before onset of clamping and through the entire clamping period. Patients with protection had a loss of their potential significantly later (20.2 min; p < 0.05) than those patients who had not received any pharmacologic treatment (15.2 min). Pharmacologic protection also resulted in a reduced incidence of postoperative neurologic deficit and paraplegia when compared with patients receiving no treatment (25% vs 5%). These data suggest that spinal evoked potentials may be very useful for monitoring during these hazardous cases. They also suggest that pharmacologic protection before clamping may help preserve the function of the spinal cord during aortic clamping. PMID- 8345372 TI - Somatosensory evoked potential, a prognostic tool for the recovery of motor function following malperfusion of the spinal cord: studies in dogs. AB - The potential usefulness of somatosensory evoked potential monitoring during aortic cross-clamping is slowly being realized. In addition, the protection of endangered spinal nervous tissue during aortic cross-clamping has not been sufficiently evaluated. To test the pharmacologic protective efficacy of various agents, we recorded spinal evoked somatosensory potentials (bipolar epidural catheter) in dogs under controlled conditions (N2O/O2-enflurane anesthesia) following clamping of the aorta for 1 hour. There were 5 groups of animals: those treated with different medications, such as prostaglandin E1 (PGE1), prostacyclin (PGI2), superoxide dismutase (SOD), and PGE1 plus SOD for pharmacologic protection during ischemia, and the controls. The time to recovery of evoked potentials during the reperfusion period was 36 minutes in the controls, 15.9 minutes in the SOD group (p < 0.01), 12.5 minutes in the PGE1 group (p < 0.001), 10.8 minutes in the PGI2 group (p < 0.001), and 3.8 minutes in the combination group (p < 0.001). In addition, treatment resulted in a better neurologic outcome on the seventh postoperative day when compared with the control group. While in the control group only 1 animal could walk (9%), 7 of 12 in the PGE1 group (58%), 4 of 12 in the SOD group (33.8%), 8 of 12 in the PGI2 group (66.7%), and all animals in the combination group (100%) could walk. We computed an exponential correlation that related the mean time of potential recovery during reperfusion with Tarlov scoring (grade 0 = paraplegia; grade 1 = paraplegia with little movements; grade 2 = paraparesis; grade 3 = paraparesis with some problems; grade 4 = normal motor function) in the various groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345373 TI - Evaluation of five small turbine-type respirometers used in adult anesthesia. AB - OBJECTIVE: The purpose of this study was to determine the accuracy of five rotating vane or turbine-type respirometers--fdE Magtrak Respiratory Monitor, fdE Haloscale Standard Wright Respirometer, Micro-Medical Pocket Monitor II, and Ohmeda 5400 and 5410 Volume Monitors--which are marketed as suitable for measuring expired gas volume in anesthetized adult patients. METHODS: The devices were tested for accuracy at simulated minute ventilations ranging from 2.4 to 15 L/min with three gas mixtures: air, air saturated with water vapor, and N2O/O2 (70:30). RESULTS: In the usual range for adult minute ventilation during general anesthesia with intermittent positive-pressure ventilation (5-12 L/min), all devices were on average accurate to within 12%. At the lowest minute volume readings (2.4 L/min) all devices except the Pocket Monitor tended to have low readings. No significant differences in readings were introduced by either saturation with water vapor or introduction of 70% N2O, except with ventilation below 4 L/min with both Ohmeda respirometers. CONCLUSIONS: All monitors showed reasonable clinical accuracy in the usual adult minute ventilation range during general anesthesia with intermittent positive-pressure ventilation (> 5 L/min) when used to measure air, water vapor-saturated air, or N2O/O2 mixtures. PMID- 8345374 TI - A reference system in clinical anesthesia. AB - We have developed, as a pilot project, a hypertext-based reference system for anesthesia in a neurosurgical clinic. The intention is to give passive decision support prior to the operation. The information is presented according to the different needs and knowledge levels of the anesthesiologists. Therefore, with the aid of a simple and universal user interface (mouse and screen keys, no keyboard) the information is structured from basic to more detailed information. To complete the operation-related material the system also offers relevant data from the "anesthesia-related background knowledge" (pre-existing diseases, drugs, and medication, etc.). As an example, a short path through the system is shown to illustrate the presentation and linkage of information. PMID- 8345375 TI - Capnography does not reliably detect double-lumen endotracheal tube malplacement. PMID- 8345376 TI - Right heart, right principle, wrong catheter. PMID- 8345377 TI - A simple index for ventriculoarterial coupling. PMID- 8345378 TI - The new health culture: tradition in turmoil. PMID- 8345379 TI - Persistent pulmonary hypertension of the newborn infant. Comparison of conventional versus extracorporeal membrane oxygenation in neonates fulfilling Bartlett's criteria. AB - Persistent pulmonary hypertension of the newborn (PPHN) is a challenge for the neonatologist and a common indication for treatment with extracorporeal membrane oxygenation (ECMO) when medical management fails. We observed 132 neonates born between January 1985 and December 1988 with the diagnosis of persistent pulmonary hypertension of the newborn: 73 (55%) met the Bartlett criteria for treatment with ECMO with 80% predicted mortality; 21 (29%) deteriorated despite conventional medical treatment, were thought to be dying, and were sent for ECMO. Among the 52 patients who were medically treated 40 (77%) survived, a marked difference compared with a predicted 20% survival. All ECMO-treated neonates survived. Although conventionally treated infants showed a trend toward less dependence on supplemental oxygen at > 28 days of life, this study failed to detect a significant difference between those two groups. We conclude that mortality was lower for ECMO-treated infants than for those who were medically treated (0 of 21 vs 12 of 52, p < 0.05); mortality for infants with persistent pulmonary hypertension of the newborn who met Bartlett's criteria and were medically treated was lower than published data; and there was no significant difference in oxygen dependence at > 28 days between the survivors who received ECMO and those who received medical therapy. PMID- 8345380 TI - Intrapartum hydramnios at term and perinatal outcome. AB - The objective of this study was to compare the intrapartum outcome among laboring patients with hydramnios (amniotic fluid index > or = 24.0 cm) versus those with adequate fluid (amniotic fluid index > 5.0 and < 24.0 cm). Prospectively, during a 2-year period, 341 patients in early labor underwent four-quadrant measurement of amniotic fluid volume. Forty-two patients had intrapartum oligohydramnios (amniotic fluid index < or = 5.0 cm) and were excluded from further analysis. The study compares the outcome between 277 subjects with adequate fluid and 22 with hydramnios. The intrapartum amniotic fluid index, birth weight, incidence of macrosomia (birth weight > or = 4000 gm), shoulder dystocia, cesarean section for fetal distress or cephalopelvic disproportion, Apgar score, and neonatal malformations were noted in each of the 299 subjects. Umbilical arterial blood gas was analyzed in 189 patients. In this study, 22 women with hydramnios had a significantly higher risk of delivering a macrosomic fetus than the 277 patients with a normal index (36.3% vs 13.7%; p = 0.01). There was no significant difference in the incidence of shoulder dystocia, cesarean section for cephalopelvic disproportion, or fetal distress, Apgar scores < 7 at 1 and 5 minutes, fetal acidosis, or neonatal anomalies. We conclude that hydramnios during the intrapartum period in patients at term is significantly associated with delivery of a macrosomic fetus, but not with delivery of a compromised neonate. PMID- 8345381 TI - User-friendly computerized quality assurance program for regionalized neonatal care. AB - In October 1983 a computerized data base system was implemented to perform quality assurance in the neonatal referral region of the University of Michigan. This system was customized to match and expand forms and reports already in use. It is menu driven, requires only rudimentary skills, and is compatible with existing computer equipment. To assess the effectiveness of the program in monitoring and improving neonatal care within the region, data from the first full year (1984) were compared with data from the last full year (1990). Statistically significant changes were found for referring physician presence at transfer, a greater assumption of initial stabilization procedures by community hospital personnel (continuous cardiorespiratory monitoring, orogastric tube placement, provision of respiratory support, blood glucose screening, blood gas evaluation, blood culturing, and antibiotic therapy), and an overall improvement in patient status before transfer. Review of reports generated by data analysis enables design of educational programs that are hospital specific and that focus on problems or deficiencies determined during quality assurance conferences. The chief benefit of this system is the provision of an objective basis for constructive criticism, which leads to both cognitive and behavioral changes in care providers and ultimately improves the delivery of care to neonates. PMID- 8345382 TI - Pump administration of exogenous surfactant: effects on oxygenation, heart rate, and chest wall movement of premature infants. AB - Adverse reactions of infants to surfactant administration include loss of chest wall movement and decrease in oxygen saturation and heart rate. We are aware of no previous studies addressing the administration of surfactant. We studied 22 infants with respiratory distress syndrome to determine whether these adverse reactions could be reduced by giving surfactant slowly by microinfusion syringe pump. Loss of chest wall movement was significantly greater in infants receiving surfactant by the hand-dosing method as compared with administration of surfactant by pump. A significant increase in ventilator pressure interventions was observed when surfactant was given by standard hand bolus method compared with pump infusion. Heart rate and oxygen saturation did not differ significantly between the two techniques. These findings suggest that pump administration of surfactant minimized potential airway obstruction; thus it may be an alternative to standard bolus dosing techniques. PMID- 8345383 TI - Increased mortality in neonates with low thyroxine values. AB - Serum thyroxine values were determined prospectively over a 6-month interval in 97 newborn infants with birth weight < 2200 gm or gestational age < 37 weeks. There were 89 survivors and 8 deaths. Infants with thyroxine values of < 2.5 micrograms/dl (32.2 nmol/L) had a significantly higher mortality rate (p < 0.001) compared with infants with higher thyroxine levels. In neonates there may exist a critical thyroxine value below which there is an increased risk of mortality. PMID- 8345384 TI - Effect of position on pulmonary mechanics in healthy preterm newborn infants. AB - Preterm infants are often placed in the supine position to facilitate care and observation. Prone positioning may positively affect later neurodevelopmental outcome, but it may also affect pulmonary function. Using a computerized system, we examined the effect of positioning on pulmonary mechanics in spontaneously breathing healthy preterm infants. Eleven infants with a mean birth weight (+/- SD) of 1523 +/- 171 gm and a mean gestational age (+/- SD) of 31.7 +/- 1.5 weeks were studied during the first 2 weeks of life. Pulmonary mechanic measurements were obtained in both supine and prone positions by mask pneumotachography and esophageal balloon technique. Respiratory rate and oxygen saturation were unaffected by positioning. There was a statistically, but not clinically, significant increase in heart rate in the prone position. However, there were no significant differences in tidal volume, minute ventilation, pulmonary resistance, or dynamic compliance between positions. The contribution of intrasubject variability of serial measurements was assessed in a separate group of four infants studied three times in the same position. There was no significant difference in respiratory rate, tidal volume, dynamic compliance per kilogram, or total pulmonary resistance in the same infant when studied in the same position over time (p > or = 0.24). The maximum variability (95% confidence limit) was 25.5% for tidal volume, 21% for dynamic compliance, and 44.3% for resistance. Because prone positioning did not adversely affect pulmonary mechanics or oxygen saturation in these healthy preterm infants, we suggest that prone position be used to facilitate the developmental needs of these infants. PMID- 8345385 TI - Failure of intrapartum antibiotics to prevent culture-proved neonatal group B streptococcal sepsis. AB - Early-onset group B streptococci (GBS-EOS) sepsis may be prevented by intrapartum antibiotics administered for GBS maternal colonization, premature labor, or prolonged rupture of membranes. We sought to identify cases of neonatal GBS sepsis after apparent failure of intrapartum chemotherapy and to determine the factors associated with failure of intrapartum antibiotics in these cases. We identified 96 GBS blood culture-positive infants at five military medical centers from 1987 to 1990. Eighteen (18.7%) of these infants had mothers who had received intrapartum antibiotics; 16 of 18 cases were early-onset disease, 15 of which initially had symptoms at less than 1 hour of age. Two infants had late-onset disease develop at 3 weeks of age. At least one perinatal risk factor (prematurity, prolonged rupture of membranes > 12 hours, maternal fever) was present in each of the 16 cases. Indications for intrapartum antibiotics were suspected chorioamnionitis (13 cases), GBS colonization and prolonged rupture of membranes or prematurity (3), and GBS colonization alone (2). Maternal antibiotics included ampicillin (14 cases), cephadyl (1), vancomycin (1), clindamycin (1), and gentamicin alone (1). The median number of doses of ampicillin before delivery was 1 (range, 1 to 21), which was administered at a median of 4 hours (range, 1 to 84) before birth. The mean dose of ampicillin was 1.8 gm/dose (range, 1 to 2 gm/dose). Two of 16 (12.5%) infants with GBS-EOS died as a result of GBS sepsis. In our population of neonates with GBS-EOS, 18.4% (16 of 87) of the infants had positive blood cultures despite intrapartum antibiotics. Intrapartum antibiotics may fail to prevent GBS sepsis in a number of infants born to mothers colonized with GBS or to those with acute chorioamnionitis. PMID- 8345386 TI - Impact of a Resource-Based Relative Value Scale fee schedule on reimbursements to neonatologists. AB - We investigated the possible effect of the Resource-Based Relative Value Scale (RBRVS) fee schedule on reimbursements for neonatologists. This payment system may prove attractive to most third-party payers and is predicted to result in lower procedural reimbursement, which is a significant component of neonatal care. We studied the charges and reimbursements for the portion of our intensive care nursery patient population covered by Medicaid for a 1-year period. Total, procedural, and nonprocedural reimbursements under three current systems and the RBRVS were compared. The RBRVS system produced overall improved reimbursement compared with Medicaid, but decreased reimbursement compared with the other two systems. Nonprocedural services were relatively better reimbursed than procedural services. The impact of RBRVS will depend on the population mix of third-party payers, the proportion of nonprocedural charges in a particular neonatal intensive care unit, and the conversion factor used by the third-party payer. PMID- 8345387 TI - New approaches for the treatment of neonatal sepsis. PMID- 8345388 TI - Subgaleal hematoma causing hypovolemic shock during delivery after failed vacuum extraction: a case report. AB - Subgaleal hematomas are potentially lethal intracranial bleedings, occurring most commonly in the neonate after difficult vacuum extraction. We report a case of hypovolemic shock occurring at birth after failed extraction and subgaleal bleeding. Subgaleal hematomas may form because of preexisting risk factors (e.g., coagulopathy), but vacuum extraction itself predisposes an infant toward subgaleal bleeding. Although the frequency of these bleedings has decreased with introduction of silicone extraction cups, the risk of subgaleal bleeding after vacuum extraction continues to be increased for primiparous women; severe dystocia, occiput lateral or posterior head presentations; and repeated, forceful, or prolonged use of vacuum suction. The presence of ballotable cranial fluid collections and signs of volume loss in a neonate raise the possibility of subgaleal bleeding. Treatment, if the subgaleal hematoma is symptomatic, requires restoration of blood volume and control of bleeding, inasmuch as these hematomas can be fatal if not treated. Prevention may require limitation of the frequency and duration of vacuum assistance in high-risk infants. PMID- 8345389 TI - Diabetic ketoacidosis after steroid administration for bronchopulmonary dysplasia: a case report. PMID- 8345390 TI - Neonatal radiology casebook. Neonatal lactobezoar. PMID- 8345391 TI - Fetal heart rate monitoring casebook. Precipitate labor and fetal heart rate monitoring. PMID- 8345392 TI - Special imaging casebook. Periventricular leukomalacia. PMID- 8345393 TI - Overestimation of neonatal PO2 by collection of arterial blood gas values with the butterfly infusion set. PMID- 8345394 TI - [Cases of lethal midline granuloma (polymorphic reticulosis) at our department in a recent 10-year period]. AB - We had 18 patients (15 males and 3 females) with lethal midline granuloma (polymorphic reticulosis) in the period from 1981 to 1990. This number was about 5.6% of the total number of patients with malignant head and neck tumors that we encountered during this period. An average of 9.1 months separated the first appearance of disease and the beginning of treatment. Most of the 18 patients underwent both radiation therapy and chemotherapy (COP, CHOP, MACOP-B), but, since their disease had reached an advanced stage, 3 underwent radiation therapy only, 3 underwent chemotherapy only, and 1 received no radical therapy at all. Of the 18 patients, 13 died of the disease. In of 6 of these, the disease was confined to the local lesion. The 5-year cumulative survival rate was 15.7% (Kaplan-Meier). Fourteen autopsy studies revealed that tumor cells had invaded the liver (92.8%), lung (92.8%) and spleen (71.4%) and in all cases it was in leukemic patterns. Fifteen cases were studied for tumor surface marker phenotype, but none was found to be positive for L26, CD43, Leu M1 (CD15), or MAC 387. Five cases were positive for UCHL-1 (CD45RO) and 10 cases were positive for lysozyme. All cases were positive for Ki-1 (CD30). PMID- 8345395 TI - [Three cases of aspiration caused by cerebrovascular disorder that were managed with total laryngectomy]. AB - Total laryngectomy can be used to prevent aspiration pneumonia in patients with severe dysphagia, though caution is required with regard to the indications. In this paper, we describe 3 patients in whom severe dysphagia developed as a result of cerebrovascular disorders, and who repeatedly developed aspiration pneumonia. We managed them with total laryngectomy, and this has prevented aspiration pneumonia in all three. Oral feeding became possible in two of these patients, and home care became possible for one. This report includes a discussion based on the literature, and includes preoperative evaluation and indications for laryngectomy. PMID- 8345396 TI - [Laryngeal control mechanisms during respiration and phonation analyzed by excitability changes of laryngeal motoneurons in decerebrate cats]. AB - Laryngeal motoneurons (LMNs) innervating the intrinsic laryngeal muscles also control glottal movements such as swallowing, respiration and phonation. The present study was performed on decerebrate cats to clarify the laryngeal control mechanisms during respiration and phonation using extracellular single unit recordings from the nucleus ambiguus. First, functional differences among LMNs during the respiratory phases were investigated by analysis of the activity of LMNs innervating laryngeal adductor (TA-LCA: thyroarytenoid-lateral cricoarytenoid) or abductor (PCA: posterior cricoarytenoid) muscles; Second, laryngeal control mechanisms during phonation were investigated by the analysis of neural activity of TA-LCA motoneurons during vocal fold vibration elicited by a constant air flow through the glottis. In both cases, motoneuronal excitability changes were expressed by measuring fluctuation of peak latencies of action potentials antidromically elicited by selective stimulation of the recurrent nerve or its peripheral branch. In 14 out of 24 TA-LCA motoneurons, neuronal excitability was increased during the expiratory phase, whereas in the remaining 10, it was increased during the later half of the inspiratory and the early half of the expiratory phase. On the other hand, 9 out of 13 PCA motoneurons showed increased neuronal excitability during the end of the expiratory and the beginning of the inspiratory phase, while the remaining 4 showed increased excitability during the inspiratory phase. These results suggest that there are functional differences among the homogeneous laryngeal motoneurons. In seven TA LCA motoneurons, neuronal excitability was decreased by vocal fold vibration elicited by phonation throughout the whole respiratory cycle. On the other hand, when the bilateral superior laryngeal nerves were cut, neuronal excitability was increased during phonation throughout the whole respiratory cycle. These results indicate that TA-LCA motoneurons receive inhibitory inputs from the superior laryngeal nerve and excitatory inputs from the recurrent laryngeal nerve during the vocal fold vibration elicited by phonation. PMID- 8345397 TI - [Idiopathic bilateral sensorineural hearing loss: clinical study of cases with rapidly progressed deafness]. AB - In a series of 127 patients with idiopathic bilateral sensorineural hearing loss (IBSH) at the Hearing Clinic in the Department of Otolaryngology, Kitasato University Hospital, 20 cases showed rapid progression of hearing impairment. These patients had been treated with the same therapeutic regimen used in sudden deafness (S.D.). Improvement of hearing loss after treatment was generally less effective in the cases with rapidly progressed IBSH than in the cases with S.D. However, hearing improvement was achieved in some cases with rapidly progressed IBSH when the treatment had started in the early stages after the onset of rapidly progressive hearing loss. The mode of fluctuating hearing loss in the cases with rapidly progressed deafness was assumed to be similar to that in the group of all cases with IBSH. PMID- 8345398 TI - [A statistical analysis of sudden deafness]. AB - The present study was carried out in order to determine factors which influenced the prognosis of sudden deafness and to try to predict the prognosis of sudden deafness, analyzed statistically by multivariate analysis. A total of 143 patients with sudden deafness diagnosed and treated at the department of otolaryngology, Ebetsu Municipal General Hospital and Obihiro Kohsei Hospital between 1986 and 1991, were selected for this study. Statistical analysis disclosed the following. 1. A good hearing level at the initial visit, a low frequency hearing loss, the absence of vestibular symptoms and an initial visit within seven days after onset, indicate a good prognosis for sudden deafness. 2. Multivariate analysis showed that the hearing level at the initial visit most strongly influences sudden deafness, followed by the number of days from onset to initial visit, vestibular symptoms and the difference between low- and high frequency hearing level, in that order. 3. Furthermore, multivariate analysis showed that the prognosis of sudden deafness can be predicted at a level of 78.3%, considering the above four factors. This facilitates treatment of patients with sudden deafness. PMID- 8345399 TI - [Changes in human spontaneous otoacoustic emissions with contralateral acoustic stimulation]. AB - According to current cochlear concepts, spontaneous otoacoustic emissions (SOAEs) are thought to be the product of outer hair cell (OHCs) movement. Furthermore, efferent neurofibers from the olivocochlear bundle primarily innervate OHCs. Thus, we designed this investigation to determine changes in SOAE under conditions of contralateral acoustic stimulation. Fouty-two normal ears of 34 subjects with uni- or bilateral SOAEs were examined. The sound pressure level (SPL) of SOAE was measured 3 times in each subject and was initially averaged. The white noises of 30 or 40dBSPL, believed not to affect the other side, were then loaded contralaterally and the SPL of SOAEs were measured and compared with the non-loaded data. The SPL of single SOAEs were actually suppressed with 40dBSPL stimulation while the SPL of multiple SOAEs showed typical changes. Interestingly, no significant suppression of SOAEs was noticed under conditions of contralateral acoustic stimulation of the impaired ear. These data suggest that contralateral acoustic stimulation could affect OHC function via the olivocochlear bundle. PMID- 8345400 TI - [Multichannel cochlear implantation in a deaf child]. AB - A multichannel cochlear implantation was performed in an 8-year-old child and the following results were obtained. The surgical procedures were not particularly difficult as compared to cochlear implantation for adults. Postoperative rehabilitation requires a longer time than in adult patients. Cochlear implants are useful not only for the recognition of environmental sound but also for the recognition of speech. Cooperation with the medical facility, as well teachers and family members, is essential. PMID- 8345401 TI - [Mild hearing loss in children with communication disorders]. AB - The prevalence of MHL in 202, 1 to 6 year-old children with communication disorders who visited our clinic in 1991 was investigated. 1) 31% of the subjects had MHL bilaterally. The prevalence of MHL was 44% at age 1 year, 20% at age 2 years, 36% at age 3 years, 24% at age 4 years, 39% at age 5 years, 33% at age 6 years. 2) 88% of children with MHL had OME, 10% had mild sensorineural hearing loss, and 2% had cerminous plug. 3) The prevalence of MHL in children with mental retardation and autistic disorders was 9%, that with stuttering was 9%, that of OME accompanied by moderate and severe hearing disorders was 6%. 4) The primary causes in 191, except for those with stuttering, were as follows; the prevalence of MHL was 30%, that of mental retardation and autistic disorders was 24%, and that of articulation disorders was 28%. 5) On the other hand, the prevalence of MHL in children with retarded language development and articulation disorders was 30%, which was significantly higher than that of the other communication disorders. Accordingly, the results of this study suggest that MHL in early childhood greatly influences communication disorders. PMID- 8345402 TI - [Antibody titers to bacterial antigens in middle ear effusion of otitis media with effusion]. AB - Antibody titers against H. influenzae, S. pneumoniae, S. pyogenes, S. mitis, S. sanguis, and S. salivarius in middle ear effusions (MEE) of 46 children (60 ears) with chronic otitis media with effusion (OME) are reported. H. influenzae, S. pneumoniae and S. pyogenes are predominant microorganisms in acute suppurative otitis media. S. mitis, S. sanguis, and S. salivarius are major species of normal adenoid flora. Specific antibodies against the above bacterial species were detected in all samples. In the chronic group, IgG titers against H. influenzae, IgG and IgM against S. pneumoniae, IgG and IgM against S. pyogenes, and IgG against S. salivarius were statistically higher than in the acute and subacute groups. IgG, IgM and IgA titers against S. mitis and S. pneumoniae in MEE with chronic sinusitis were higher than those from sinusitis free children. Anti-S. sanguis and S. pyogenes IgG and IgA of sinusitis free patients' MEE were higher than those with chronic sinusitis. The antibody titers against H. influenzae did not differ statistically between those with and without sinusitis. The presence of anti-bacterial antibodies inhibits acute infection in MEE, and the difference in titers with sinusitis may be caused by bacterial numbers in the adenoids and the host's response to the bacteria. PMID- 8345403 TI - [Bacterial quantification and anti-bacterial antibodies in otitis media with effusion in children]. AB - Quantification of bacterial flora in middle ear effusions (MEE) and adenoids in children with otitis media with effusion (OME) was performed. IgG, IgA and IgM titers against H. influenzae, S. pneumoniae, S. mitis, S. sanguis, and S. salivarius were measured in MEE, sera and the supernatant of adenoid lymphocyte cultures. The adenoid lymphocytes were stimulated by each inactivated bacteria species for 7 days, before antibody titers were measured. Seven species were detected in 6 of 18 MEE samples (33.3%). Six of these species were also detected in the adenoids of the same cases. Bacterial identification of flora in adenoids was as follows. S. pneumoniae: 8, H. influenzae: 4, B catarrhalis: 4, S. mitis: 9, S. sanguis: 8, S. salivarius: 12 of cases. The antibody titers against bacteria from adenoids in MEE and the supernatant were significantly higher than those of the group in which no species were detected. These specific antibodies in MEE inactivate bacteria from the adenoid, but the immune complex probably plays some part in chronic inflammation of the middle ear. PMID- 8345404 TI - [Changes in the utricular otoconia of the chick embryo developed under 2G gravity]. AB - Whether or not vestibular adaptation occurs upon exposure to altered gravity is an important human problem. Studies have been performed to ascertain whether morphological changes in vestibular organs occur in animal models upon exposure to microgravity. On the other hand, the morphological changes which occur in vestibular organs under hypergravity have not yet been fully elucidated and morphological changes in the otoconia of the chick embryo exposed to hypergravity during the embryonic period remain to be thoroughly examined. The purpose of this paper is to clarify the effects of hypergravity on vestibular organs, especially its effects on otoconial formation in the developing chick embryo. Thus, we designed an apparatus which creates artificial gravity, creating approximately 2G gravity by means of centrifugation. The utricular macula was chosen for study because it can be prepared for examination with a minimum of dissection artifacts. The data presented show that morphological changes were confined to otoconial size alterations according to scanning electron microscopic observations. Giant otoconia were observed along the marginal zones of utricle . PMID- 8345405 TI - Academic departments of histopathology and the UFC research selectivity exercise. PMID- 8345406 TI - C. L. Oakley Lecture (1993). Cellular and molecular aspects of hepatic fibrosis. AB - Hepatic fibrosis, a consequence of most forms of chronic liver disease, is a dynamic process involving complex interactions between several cell types, the net result of which is accumulation of several distinct extracellular matrix (ECM) proteins. The resultant disruption of intrahepatic blood flow contributes to the development of portal hypertension. The effects, however, are not merely a space-occupying phenomenon; by changing the composition of the ECM, fibrosis may also alter hepatocyte function via cellular integrins. The principal source of ECM proteins in normal and fibrotic liver is the perisinusoidal cells which lie in the space of Disse. The response of this cell population to acute and chronic liver injury has been studied in detail. Perisinusoidal cells proliferate and become activated following hepatocyte necrosis. This phenomenon is transient in acute injuries, but in chronic liver disease, continued activation is associated with phenotypic modulation of perisinusoidal cells to myofibroblasts. This process is mediated by various cytokines including TGF-beta and PDGF. Some of the growth factors involved are derived from activated Kupffer cells and there is evidence of a complex interplay between mediators; injured sinusoidal endothelial cells and platelets are possible additional sources. Accumulation of ECM proteins in fibrosis can be explained not only by increased synthesis, but also by decreased degradation. There is growing evidence that in fibrotic liver there is decreased interstitial collagenase activity. This is, at least in part, due to expression of a tissue inhibitor of metalloproteinase, TIMP-1, by activated perisinusoidal cells. PMID- 8345407 TI - An immunohistological study of cutaneous lymphocytes in vitiligo. AB - In a study of 49 biopsies from the margins of depigmented cutaneous lesions in 18 patients with vitiligo, highly significant overall increases were found in CD3+, CD4+, and CD8+ T cells, though cell numbers in individual cases were often within the normal range. Many of the T cells were activated (MHC class II+, interferon gamma+), of CD45RO (UCHL1+) memory subset, and many expressed the cutaneous lymphocyte-associated antigen (HECA-452+) typical of skin-homing T cells. Immunohistologically, the most intense epidermal T-cell infiltration was present within 0.6 mm of the edge of the lesion in 10 of 13 double-stained sections with a clearly defined zone of melanocyte depletion. In 40 lesions from 17 patients seen 11-64 weeks after biopsy, no apparent association was found between T-cell numbers and disease activity as assessed by Kobnerization of biopsy wounds or spread of depigmentation. These findings are consistent with the hypothesis that lesional T cells rather than circulating antimelanocytic antibody may be responsible for the supposedly autoimmune but characteristically patchy destruction of cutaneous melanocytes in vitiligo. Nevertheless, many of the infiltrating T cells are probably innocent bystanders attracted by upregulated cell adhesion molecules near sites of melanocyte damage. PMID- 8345408 TI - Participation of macrophages in segmental endocapillary proliferation preceding focal glomerular sclerosis. AB - We studied infiltrating cells in the glomeruli of eight cases with focal segmental endocapillary proliferation (FSEP) using monoclonal antibodies to leukocyte common antigen, T cells, B cells, and monocytes/macrophages (Mo/M psi). It was demonstrated by sequential biopsies performed in five cases that FSEP preceded focal glomerular sclerosis (FGS). Cell types in FSEP were compared with those in FGS from 17 patients with persistent nephrotic syndrome, ten non nephrotic patients, and eight patients with nephrotic syndrome which was initially responsive to steroid therapy but relapsed, as well as minimal change specimens from nine nephrotic patients. In the glomeruli, the mean total leukocyte counts increased significantly in the FSEP group (P < 0.01). The serial sections in FSEP revealed that Mo/M psi were the predominant cells and were localized in areas of endocapillary proliferation. T-cell or B-cell infiltration was less marked. The extensive intracapillary distribution of p150,95 antigen belonging to the integrin family and acting as a C3bi receptor suggested that FSEP may be mediated by adhesion molecules expressed on Mo/M psi. These findings indicate that Mo/M psi may play a key role in FGS which shows endocapillary proliferation in the initial stage. PMID- 8345410 TI - Scatterbrain fetus. PMID- 8345409 TI - Immune complex degradation by cultured rat mesangial cells. AB - The binding and degradation of radiolabelled immune complexes by cultured rat glomerular mesangial cells were measured and compared with the binding and degradation by thioglycollate-elicited rat peritoneal macrophages. Mesangial cells are generally considered to be a modified pericyte with smooth muscle-like properties, but they were able to bind and degrade soluble immune complexes at rates comparable to those of the macrophages. In a second study, the ability of cultured mesangial cells to bind and degrade immune complexes of varying molecular weight was assessed. Very large, insoluble complexes were found to bind to mesangial cells more avidly than small soluble complexes, but unlike the small complexes, the large complexes did not appear to undergo degradation. These findings support a role for the intrinsic mesangial cell in the elimination of small soluble immune complexes as they arrive in the glomerulus. They also provide a possible explanation for the paradox that large immune complexes--i.e., electron-dense deposits--can persist in the mesangium next to the intrinsic mesangial cells without being rapidly destroyed. PMID- 8345411 TI - Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management. AB - Familial combined hyperlipidemia (FCHL) is a dominantly inherited hyperlipidemia that occurs in at least 1% of the adult population and is responsible for 10% of premature coronary artery disease. In families referred for evaluation because of primary hyperlipidemia in a child, FCHL is expressed three times more commonly than familial hypercholesterolemia and half of the siblings are affected. Several metabolic defects apparently are associated with the FCHL phenotype. Most commonly, excess production of very low density lipoprotein apolipoprotein B can be demonstrated. In other families, reduced lipoprotein lipase activity is associated. One allele at a locus influencing apolipoprotein B levels predicts FCHL in a large proportion of families ascertained through affected children. Whether this allele is responsible for the excess of very low density lipoprotein apolipoprotein B detected in metabolic studies has not been elucidated. Management of FCHL in children begins with dietary modification. A bile acid sequestrant may be considered as well if diet cannot reduce the plasma low density lipoprotein cholesterol level to less than 4.13 mmol/L (160 mg/dl) after the age of 10 years. Although the hydroxymethylglutaryl-coenzyme A reductase inhibitors are not currently recommended for children younger than 19 years of age, we speculate that they will be increasingly utilized for the management of FCHL in teenage boys who continue to have low density lipoprotein cholesterol levels greater than 4.13 mmol/L (160 mg/dl) after dietary modification. PMID- 8345413 TI - Energy expenditure during walking and running in obese and nonobese prepubertal children. AB - We measured body composition and energy expenditure during walking and running on a treadmill in 40 prepubertal children: 23 obese children (9.3 +/- 1.1 years of age; 46 +/- 10 kg (mean +/- SD)) and 17 nonobese matched control children (9.2 +/ 0.6 years of age; 30 +/- 5 kg). Energy expenditure was assessed by indirect calorimetry with a standard open-circuit method. At the same speed of exercise, the energy expenditure was significantly (p < 0.01) greater in obese than in control children, in both boys and girls. Expressed per kilogram of body weight or per kilogram of fat-free mass, the energy expenditure was comparable in the two groups. Obese children had a significantly (p < 0.01) larger pulmonary ventilatory response to exercise than did control children. Heart rate was comparable in boys and girls combined but significantly higher (p < 0.05) in obese subjects, if boys and girls were analyzed separately. These data indicate that walking and running are energetically more expensive for obese children than for children of normal body weight. The knowledge of these energy costs could be useful in devising a physical activity program to be used in the treatment of obese children. PMID- 8345412 TI - Association among serum lipid and lipoprotein concentrations and physical activity, physical fitness, and body composition in young children. AB - OBJECTIVE: To examine the relationships among indicators of physical activity, physical fitness, and body composition with serum lipid and lipoprotein levels in young children. DESIGN: Cross-sectional and 1-year prospective cohort. SETTING: Studies of Child Activity and Nutrition (SCAN) program, Galveston, Tex. SUBJECTS: One hundred twenty-three 4- or 5-year-old black, Hispanic (of Mexican origin), and white children. MEASUREMENTS: Body composition, resting heart rate, and cardiovascular fitness variables and serum lipid and lipoprotein levels were measured at age 3 or 4 years (study year 1) and at age 4 or 5 years (study year 2), and day-long heart rate was measured and the Children's Activity Rating Scale was administered between study years 1 and 2. RESULTS: Year-1 waist/hip ratios were inversely correlated with total serum cholesterol (TSC) and low-density lipoprotein (LDL) levels. Mean activity level was inversely correlated with waist/hip ratios. On the basis of multiple regression analysis, the sum of seven skin-fold measurements, height, and gender explained 15.4% of the variation in triglyceride levels. The sum of seven skin-fold measurements was inversely correlated with the high-density lipoprotein (HDL) level. Resting heart rate, waist/hip ratio, and the slope of the exercise heart rate during fitness testing explained 19.5% of the variation in the concentration of an HDL subclass, HDL2. These children's levels of physical activity were associated with higher fitness levels. Year-1 waist/hip ratios and year-2 sum of seven skin-fold measurements were positively correlated with the LDL/HDL and TSC/HDL ratios. CONCLUSION: Higher levels of cardiovascular fitness and lower levels of fatness were associated with more favorable serum lipid and lipoprotein levels in these young children. Physical activity appeared to have an indirect association with serum lipid and lipoprotein values through its relationship with higher fitness levels and lower levels of fatness. PMID- 8345414 TI - Daily energy expenditure by five-year-old children, measured by doubly labeled water. AB - Current recommendations for daily energy requirements in 5-year-old children (90 kcal/kg per day) are based on energy intake associated with normal growth. It is not known, however, how these recommendations compare with total free-living energy expenditure (TEE) and how much of TEE is related to physical activity. The TEE and the resting metabolic rate (RMR) were measured in 28 white children, aged 5 years (15 boys, 13 girls; mean (+/- SD) weight 20.1 +/- 3.4 kg; height 113 +/- 6 cm; fat 20% +/- 5%). The TEE was calculated during a 7-day period from urinary elimination rates of deuterium (2H) and heavy oxygen (18O) by using a modification of the two-point slope-intercept method; RMR was measured by a ventilated-hood indirect calorimeter. Physical activity indexes were also collected from questionnaires completed by the parents. Measured TEE was considerably lower than the recommended dietary allowances (1370 +/- 222 kcal/day vs 1807 +/- 310 kcal/day; p < 0.0001), whereas measured RMR was slightly higher than predicted RMR (1001 +/- 119 kcal/day vs 952 +/- 78 kcal/day; p < 0.001). The energy cost of physical activity accounted for only 16% +/- 7% of TEE. An index of activity, assessed as the difference between the measured TEE and the predicted TEE, correlated positively with past-year sport-leisure activity assessed by questionnaire (r = 0.40; p < 0.05). We conclude that measured TEE in 5-year-old children yields lower values (approximately 400 kcal/day) than current estimates. A minute part of this difference (20 to 30 kcal/day) is related to the changes in energy stores during growth, but most seems due to lower-than-expected levels of physical activity. This might be related to increased television viewing, which replaces activities requiring energy. PMID- 8345415 TI - Oxygen consumption-oxygen delivery relationship in children. AB - We examined the relationship between oxygen consumption (VO2) and oxygen delivery (DO2) over a range of metabolic demand in two groups of children. We studied 15 children after cardiac surgery (plasma lactate levels < 2.2 mmol/L, VO2 < 6 ml/min per kilogram, oxygen extraction ratio < 25%); 8 were given transfusions with erythrocytes, 10 to 15 ml/kg, and 7 received adrenaline infusions (0.05 to 0.3 micrograms/kg per minute). Blood transfusions significantly increased DO2 (20.5 +/- 6.4 to 26.2 +/- 7.1 ml/min per kilogram; p < 0.05) but did not alter VO2. Adrenaline increased DO2 (19.9 +/- 5.0 to 25.9 +/- 6.1 ml/min per kilogram; p < 0.05) and VO2 (4.3 +/- 0.8 to 5.5 +/- 1.2 ml/min per kilogram; p < 0.05), but the oxygen excretion ratio and the mixed venous oxygen saturation were unchanged. We also measured VO2 and Doppler-derived DO2 in 25 normal children during exercise. The relationship during exercise is given by the following equation: VO2 index (in milliliters per minute per kilogram) = 0.88 x DO2 index - 6.95. Adrenaline infusions, but not blood transfusions, increased VO2 and DO2 together. This effect may be due to increased demand, analogous to exercise, and probably does not represent improved perfusion. We also found significant measurement error in DO2 and spontaneous variation in VO2. We believe that the concept of supply-dependent VO2 is based on a number of methodologic and measurement errors. It should not be used to justify potentially dangerous therapies in sick children. PMID- 8345416 TI - Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy. AB - Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height. It is yet unknown whether therapy would alter pubertal development or affect final height. Three-year treatment results in a group of children with idiopathic short stature are reported. For year 1 of the study, 121 prepubertal children were randomly selected to receive somatotropin, 0.3 mg/kg per week, administered subcutaneously three times weekly (n = 63), or to be nontreatment control subjects (n = 58). After 1 year, all subjects were again randomly selected to receive either three times-weekly or daily dosing at the same total dose. For the 92 subjects who completed 36 months of treatment, mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment. Daily dosing resulted in a significantly faster mean growth rate (9.0 cm/yr) than three-times-weekly dosing (7.8 cm/yr) (p = 0.0005). Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3, respectively, and did not differ by dosing group. Mean standardized height for all subjects improved from -2.7 to -1.6 after 3 years. When the growth rate was standardized for bone age, however, subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period (p < 0.02). Mean standardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset, but for individuals this score was more variable. Year-1 growth response, expressed as growth rate or change in height SD score, was the best predictor of growth in subsequent years. Responses to therapy could not be reliably predicted from baseline anthropometric variables, plasma insulin-like growth factor I SD score, growth hormone levels. Final height assessment will be needed to determine the ultimate benefit of therapy. PMID- 8345417 TI - Prematurity as a risk factor for asthma in preadolescent children. AB - Information on long-term respiratory symptoms in prematurely born children is scanty. We studied an unselected population of 9- to 11-year-old schoolchildren. A self-administered questionnaire was distributed to the parents. Children underwent lung function testing, cold air challenge, and skin prick tests. A gestational age < 37 weeks in children with a birth weight < or = 2500 gm was reported by 5% of the parents. Premature girls had significantly more current asthma (odds ratio (OR) 2.6; 95% confidence interval (CI) 1.4, 4.7; p < 0.05), recurrent wheezing (OR 1.7; 95% CI 1.1, 2.7; p < 0.001), recurrent shortness of breath (OR 2.4; 95% CI 1.5, 3.9; p < 0.001), and frequent cough with exercise (OR 1.8; 95% CI 1.1, 2.9; p < 0.05) than term girls, especially if they required mechanical ventilation after birth. No such differences could be shown in boys. More prematurely born children who required mechanical ventilation (OR 3.7; 95% CI 2.2, 6.4; p < 0.0001) had a family history of asthma than children born at term. Significant decrements could be demonstrated for different measurements of lung function in premature girls. These results remained significant after control for confounders in a multivariate regression analysis. No difference was found between groups for bronchial hyperresponsiveness to cold, dry air or for atopic sensitization. We conclude that a family history of asthma may predispose premature children to more severe respiratory disease. Respiratory symptoms and decrements in lung function seen in girls may reflect abnormalities of lung function in survivors of severe neonatal respiratory disease. PMID- 8345418 TI - Cerebral palsy in four northern California counties, births 1983 through 1985. AB - To examine the impact of demographic shifts and changes in perinatal medicine on the distribution of cerebral palsy (CP), we investigated characteristics of affected children in a large, recent population-based American cohort study. Children with moderate or severe congenital CP born in four northern California counties in 1983 through 1985 and surviving to age 3 years were identified through records of state service agencies and clinical examination or record review by a single physician. We compared information from birth certificates for 192 children with CP and 155,636 survivors without CP born in those counties in the same period. Children with birth weights < 2500 gm contributed 47.4% of the CP in this population; those < 1000 gm, who were 0.20% of survivors, contributed 7.8%. Children with birth weights of 4000 to 4500 gm were at lowest risk. Among singletons, prevalence of CP was lowest (0.92/1000) in infants born to women aged 25 to 34 years, and was significantly higher in children whose mothers were 40 years or older (3.3/1000), especially if they were high in parity (6.9/1000). Children of teenaged mothers or fathers were at somewhat increased risk of CP. Early gestational age at birth was also an important independent risk factor. Prevalence of CP was slightly higher in black children, apparently related to a greater tendency to be low in birth weight. The time during pregnancy when prenatal care began was similar for children with CP and for the general population. For the 95% of children born weighing > or = 2500 gm, birth in a hospital lacking a special care nursery was not associated with increased risk of CP. Almost 8% of CP occurred in children born weighing < 1000 gm, a group that produced few survivors in the past; 28.1% occurred in children born weighing < 1500 gm. Neither early initiation of prenatal care nor, for that large majority of neonates weighing > 1500 gm, delivery at a hospital with specialized facilities was associated with a lower risk of CP. PMID- 8345419 TI - Iron overload in children receiving prolonged parenteral nutrition. AB - This study was carried out to evaluate the iron status of 30 children aged 1 to 18 years who had been receiving total parenteral nutrition (TPN) for an average of 43 months with iron intakes of 100 micrograms/kg per day. Iron status was assessed by assaying the serum iron and ferritin levels and the transferrin saturation coefficient as a function of iron intake. Liver biopsy specimens were taken from 13 children. Twelve children had serum ferritin levels greater than 300 ng/ml, and 8 had levels greater than 800 ng/ml. The serum ferritin level and the transferrin saturation coefficient were positively correlated (r = 0.81; p < 0.01). The serum ferritin level was positively correlated with TPN duration and with the total iron intake (r = 0.68; p < 0.01). Of the 13 liver biopsy specimens, six showed signs of iron deposition. We conclude that there is a risk of iron overload in children receiving 100 micrograms iron per kilogram of body weight per day by TPN, indicating that intake should be reduced. PMID- 8345420 TI - Urinary oxalate and glycolate excretion patterns in the first year of life: a longitudinal study. AB - To determine the range of normal values, we studied urinary excretion of oxalate and glycolate prospectively and longitudinally in a cohort of 30 healthy term infants. Random urine samples were obtained at 2 days, 2 weeks, and 2, 4, 6, and 9 months of age. The results had a log-normal distribution. The mean oxalate/creatinine ratio, as determined by the oxalate oxidase method, was 0.08 (in milligrams of oxalate to milligrams of creatinine) with a normalized range of 0.02 to 0.31. The mean ratio when oxalates were measured by using the Olthuis assay was 0.13 (range 0.03 to 0.53). The mean glycolate/creatinine ratio was 0.07 (range 0.02 to 0.26). These values did not correlate with increasing age. The oxalate/creatinine ratios were higher in formula-fed infants than in those who were fed human milk (0.14 +/- 0.16 vs 0.08 +/- 0.04; p < 0.01). PMID- 8345421 TI - Identifying human immunodeficiency virus infection at birth: application of polymerase chain reaction to Guthrie cards. AB - Guthrie cards containing dried blood spots from 67 children now known to be infected with human immunodeficiency virus (HIV) and 63 children now classified as having had seroreversion were retrieved from the newborn infant archives from 1986 through 1991 to determine whether the polymerase chain reaction (PCR) could predict the infection at birth. The PCR assays operating at a sensitivity capable of detecting 2 to 10 copies of HIV proviral DNA per microgram were able to detect HIV proviral DNA in 52% (35/67) of the infected neonatal blood specimens. Longer storage times did not decrease PCR positivity rates, an advantage over assays for HIV antibody. Children whose clinical progression has been aggressive had high rates of PCR positivity in neonatal specimens, 50% (7/14) in those with low CD4 cell counts during the first year of life, 71% (10/14) in those with Pneumocystis pneumonia or disseminated cytomegalovirus infection by age 1 year, 62% (18/29) in those with onset of acquired immunodeficiency syndrome by 18 months, and 66% (14/21) in those who died of the disease by 36 months of age. No evidence of HIV proviral DNA was found in any of the 63 specimens from children with seroreversion. We conclude that PCR, using routinely available dried blood spots from neonates, has applications in early diagnosis and in epidemiologic projections going beyond current seroprevalence studies. PMID- 8345422 TI - A rapid test for the detection of human immunodeficiency virus antibodies in cord blood. AB - A commercially available rapid test (HIVCHEK) was compared with an enzyme-linked immunosorbent assay (ELISA) for identifying human immunodeficiency virus type 1 in the serum of newborn infants. Of 1309 cord blood samples tested, the HIVCHEK test detected all the true-positive samples detected by ELISA. Of the 35 samples with positive ELISA results, six had negative results on Western blot; only 1 of the 30 samples with positive HIVCHEK results had negative results on Western blot. Thus the HIVCHEK test can be used to facilitate the rapid identification of HIV-1 in the serum of newborn infants. PMID- 8345423 TI - Incidence of celiac disease identified by the presence of serum endomysial antibodies in children with chronic diarrhea, short stature, or insulin-dependent diabetes mellitus. AB - We determined the incidence of celiac disease in the western New York area to be 1.29 per 10,000 live births. Celiac disease occurred in 29 children with gastrointestinal symptoms. Two children (1.7%) of 117 with short stature and 10 (4.0%) of 211 with diabetes mellitus had serum anti-endomysial antibodies. We conclude that the incidence of childhood celiac disease in our area is much less than that reported in Europe. PMID- 8345424 TI - Malignant osteopetrosis treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma. AB - A male infant with malignant osteopetrosis was treated with high doses of 1 alpha hydroxyvitamin D3 and interferon gamma. Therapy with 1 alpha-hydroxyvitamin D3 increased the serum calcium level despite the markedly elevated serum level of 1 alpha, 25-dihydroxyvitamin D before treatment. Recombinant human interferon gamma increased neither the bone mineral nor matrix turnover, and was not tolerated because of bone marrow suppression. PMID- 8345425 TI - Widespread hemangiomatosis of bone associated with rickets: recovery after irradiation. AB - We describe a 15-year-old boy with hemangiomatosis of bone and hypophosphatemic rickets. The rickets was ameliorated by irradiation of the skeletal lesions. PMID- 8345426 TI - Alveolar-arterial oxygen gradient in acute chest syndrome of sickle cell disease. AB - In 44 episodes of acute chest syndrome of sickle cell disease occurring in 37 children, simple clinical severity score, duration of hospital stay, transfusion data, and alveolar-arterial oxygen gradient were analyzed as indicators of severity of disease. The alveolar-arterial oxygen gradient, measured during breathing of room air, proved, on multivariate analysis, to be the strongest predictor of both clinical severity and the need for blood transfusion. PMID- 8345427 TI - Lysinuric protein intolerance with chronic interstitial lung disease and pulmonary cholesterol granulomas at onset. AB - Hyperammonemia and encephalopathy developed in an 11-year-old girl with chronic interstitial lung disease and cholesterol casts in her lung biopsy specimen. She had decreased plasma levels of ornithine, lysine, and arginine and excessive urinary excretion of lysine and arginine, consistent with the diagnosis of lysinuric protein intolerance. Analysis of plasma and urinary amino acids should be considered in the diagnostic evaluation of patients with interstitial lung disease of uncertain origin. PMID- 8345428 TI - Suppression of erythropoiesis by intrauterine transfusions in hemolytic disease of the newborn: use of erythropoietin to treat the late anemia. AB - Hemolytic disease of the fetus and newborn has three phases of anemia: in utero, in the first week of life, and in the weeks and months after birth. Intrauterine transfusions can ameliorate the severity of both fetal and early anemia, but late anemia and the need for transfusion remain significant problems. Bone marrow hypoplasia--probably a result of suppression of erythropoiesis from the intrauterine transfusions--was documented in the three patients tested in our study. Because erythropoietin (EPO) levels have been found to be low (i.e., normal) in these previously transfused patients despite the degree of anemia, we treated four affected infants with EPO, 200 microliters/kg subcutaneously three times a week, and noted reticulocytosis and increased hemoglobin values 2 to 4 weeks later. One patient again had reticulocytopenic anemia when the EPO therapy was stopped but responded to retreatment. Our study indicates that EPO treatment may be effective in the management of late anemia and could help to decrease the need for postnatal transfusions. PMID- 8345429 TI - A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. AB - A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were randomly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates (10 ml/kg). The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions. In 22 (28%) of the 78 treated infants and 19 (26%) of the 74 control infants, either a new intracranial hemorrhage developed or an already-present one became more extensive (p = 0.73). Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography. Similar numbers of infants received fresh frozen plasma and packed red blood cells, but treated infants received less of both. The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened (mean difference, 79.0; 95% confidence interval, 73.1 to 84.9). Subanalysis of the control group showed that infants with platelet counts < 60 x 10(9)/L (n = 21) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345430 TI - Production of tumor necrosis factor by human cells in vitro and in vivo, induced by group B streptococci. AB - Tumor necrosis factor alpha (TNF alpha) has been implicated as one of the major mediators of the gram-negative septic shock syndrome. In our studies, group B streptococci (GBS) induced the production of TNF alpha by human mononuclear cells in a dose- and time-dependent manner. Human mixed mononuclear cell cultures exposed to an encapsulated (657.6 +/- 71.3 pg/ml; n = 30 preparations) or an unencapsulated transposon mutant of type III GBS (755.8 +/- 54.7 pg/ml; n = 9) produced similar amounts of TNF alpha. Isolated monocytes and culture-derived macrophages produced higher amounts of TNF alpha (1565 +/- 211 and 1790 +/- 928 pg/ml respectively) in response to GBS than did mixed mononuclear cell cultures. In response to GBS, mixed mononuclear cells from neonates produced significantly more TNF alpha (729.1 +/- 45 vs 520.3 +/- 47.2 pg/ml; p = 0.004) than did cells from adults. Examination of specimens from patients with neonatal GBS disease revealed detectable levels of TNF alpha (7 to 424 pg/ml) in the serum of 5 of 10 patients with sepsis, in 5 of 5 urine samples from infants with sepsis, and in the cerebrospinal fluid of 1 patient with meningitis. These results suggest both a major role for TNF alpha in the pathogenesis of human neonatal GBS sepsis and shock and a potential role for immunotherapy directed against this cytokine in this fulminant neonatal bacterial infection. PMID- 8345431 TI - Effect of intrauterine growth retardation on postnatal weight change in preterm infants. AB - To investigate the cause or causes of early postnatal weight change, we measured total body water and fluid and energy balances in 14 preterm infants who were appropriate in size for gestational age (AGA) and in 5 weight-matched, preterm, small-for-gestational-age (SGA) infants. On the first day of life, AGA and SGA infants had the same weight and total body water content. At 6 +/- 2 days (mean +/- SD), AGA infants had had significant weight loss (94 +/- 45 gm) and body water loss (67 +/- 80 ml), whereas weight and total body water content in the SGA infants at the same age (5 +/- 1 days) did not differ from the values at birth. Loss of weight and total body water in AGA infants was accompanied by a greater diuresis than in SGA infants at the same amount of fluid intake. At the end of week 1, AGA and SGA infants had the same total energy expenditure (184 +/- 33 vs 171 +/- 17 kJ.kg-1 x day-1); energy intake, which had exceeded total energy expenditure from the third day of life and beyond, already provided 188 +/- 46 (AGA) or 209 +/- 109 kJ.kg-1 x day-1 (SGA), respectively, for energy storage. Nitrogen balance was positive. Subsequent weight gain occurred at the same rate in AGA and SGA infants; both total body water and solids increased. Energy intake, total energy expenditure, and the amount of energy stored (measured during stable weight gain on a regimen of full enteral feedings) had significantly increased compared with week 1, but both groups maintained similar energy storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345432 TI - Expected duration of hospital stay of low birth weight infants: graphic depiction in relation to birth weight and gestational age. AB - Neonatal duration of hospital stay correlated with both birth weight and gestational age in positively skewed, nonlinear relationships. Within increments of birth weight, gestational age had a semi-independent influence on length of stay. Log length of stay correlated with both birth weight and gestational age in linear, normally distributed relationships. A nomogram is provided for predicting individual lengths of stay. PMID- 8345433 TI - Standardization of prothrombin times in newborn infants. AB - The prothrombin time (PT) for patients receiving warfarin varies widely, reflecting the heterogeneity of thromboplastin reagents. The International Committee on Thrombosis and Haemostasis recommends that PT values for these patients be expressed as international normalized ratios. This study showed that thromboplastin reagents also significantly influence PT values in neonatal plasma and that expressing PT values as international normalized ratios decreases this variability. PMID- 8345434 TI - Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. AB - The aim of this study was to compare the response to inhaled albuterol after administration by nebulizer with the response after administration by a metered dose inhaler and spacer device (MDI-spacer) to children with acute asthma. In a double-blind fashion, 33 children (6 to 14 years of age) with forced expiratory volume in 1 second (FEV1) between 20% and 70% of predicted values, and who were seen in the emergency department with acute asthma, were studied. They were treated with aerosolized albuterol or placebo by MDI-spacer, followed immediately by albuterol or placebo administered by nebulizer with oxygen. The dose ratio for albuterol by MDI-spacer versus nebulizer was 1:5. Outcome measures included a clinical score, respiratory rate, arterial oxygen saturation, and FEV1, measured before and 10, 20, and 40 minutes after treatment. With the exception of heart rate (which increased in the nebulizer group and decreased in the MDI-spacer group (p < 0.05), no difference in the rate of improvement of clinical score, respiratory rate, arterial oxygen saturation, or FEV1 was noted during the 40 minute study period between children who received albuterol by nebulizer and those who received it by MDI-spacer. We conclude that spacers and nebulizers are equally effective means of delivering beta 2-agonists to children with acute asthma. PMID- 8345436 TI - Death from a morphine infusion during a sickle cell crisis. AB - A 15-year-old boy died during a vaso-occlusive sickle cell crisis after having received a prolonged infusion of morphine. Even in therapeutic doses, narcotics may cause significant respiratory acidosis and hypoxemia, enhancing polymerization of hemoglobin SS and thereby promoting sickling and vaso occlusion. When narcotics are used during a sickle cell crisis, the best method is pharmacokinetically based patient-controlled analgesia. PMID- 8345435 TI - Hepatotoxic effects in a child receiving valproate and carnitine. AB - L-Carnitine supplementation has been recommended to prevent the fatal hepatotoxic effects associated with valproic acid. We report on a child with fatal valproate related hepatotoxic effects despite this supplementation. PMID- 8345437 TI - Mineral balance and bone turnover in adolescents with anorexia nervosa. AB - We evaluated seven female adolescents with anorexia nervosa to determine whether calcium metabolism was affected by their disorder. We measured calcium absorption, urinary calcium excretion, and calcium kinetics, using a dual-tracer, stable-isotope technique during the first weeks of an inpatient nutritional rehabilitation program. Results were compared with those from a control group of seven healthy adolescent girls of similar ages. The percentage of absorption of calcium was lower in subjects with anorexia nervosa than in control subjects (16.2% +/- 6.3% vs 24.6% +/- 7.2%; p < 0.05). Urinary calcium excretion was greater in subjects with anorexia nervosa than in control subjects (6.4 +/- 2.5 vs 1.6 +/- 0.7 mg.kg-1 x day-1; p < 0.01) and was associated with bone resorption rather than calcium hyper-absorption. Calcium kinetic studies demonstrated a decreased rate of bone formation and an increased rate of bone resorption. These results suggest marked abnormalities in mineral metabolism in patients with anorexia nervosa. From these results, we hypothesize that improvement in bone mineralization during recovery from anorexia nervosa will require resolution of hormonal abnormalities, including hypercortisolism, in addition to increased calcium intake. PMID- 8345438 TI - Hydramnios in pseudohypoaldosteronism versus hypoaldosteronism in neonates. PMID- 8345439 TI - Thyroxine-binding globulin deficiency misdiagnosed as hypothyroidism. PMID- 8345440 TI - Treatment of hyperprostaglandin E syndrome with indomethacin. PMID- 8345441 TI - Local reactions to depot leuprolide therapy for central precocious puberty. PMID- 8345442 TI - Errors in citations in foreign languages. PMID- 8345443 TI - Development of a scale measuring genetic variation related to expressive control. AB - It has been theorized that a substantial genetic component underlies the Self Monitoring Scale. The identity of this component, however, is not yet known. In order to identify and better understand it, a more precise measure of the component is required. The present research attempted to (a) identify an axis of the self-monitoring two-factor space with maximum genetic variance; and (b) bootstrap a scale more highly correlated with this genetic maximum than is the Self-Monitoring Scale using twins. Evaluation of the new scale against criteria of validity indicates that scale construction was reasonably successful. The new measure had a cross-validated monozygotic twin intraclass correlation of .76 and a dizygotic twin intraclass correlation of .16. This work yields a new research tool and suggests a new approach to personality assessment. Correlates of the new measure as well as theoretical and methodological issues relevant to the measurement of a latent genetic entity are discussed. PMID- 8345445 TI - Analyzing individual status and change with hierarchical linear models: illustration with depression in college students. AB - A recently developed class of multilevel or hierarchical linear models (HLM) provides an intuitive and efficient way to estimate individual growth or change curves. The approach also models the between-subjects variation of the individual change curves with treatment factors and individual attributes. Unlike other repeated measures analysis methods common in the behavioral sciences, HLM allows the fit of data with unequal numbers of repeated observations for each subject, variable timing of observations, and missing data, features which are often characteristic of data from field studies. The application of HLM for the analysis of repeated psychological measures is discussed and illustrated here with depression data for college students. Strengths and limitations of the approach are discussed. PMID- 8345444 TI - Genetic and environmental effects on openness to experience, agreeableness, and conscientiousness: an adoption/twin study. AB - Previous research has indicated that extraversion and neuroticism are substantially affected both by genotype and environment. This study assesses genetic and environmental influences on the other three components of the five factor model of personality: Openness to Experience, Agreeableness, and Conscientiousness. An abbreviated version of the NEO Personality Inventory (NEO PI) was administered to 82 pairs of identical twins and 171 pairs of fraternal twins reared apart and 132 pairs of identical twins and 167 pairs of fraternal twins reared together. Estimates of genetic and environmental effects for Openness and Conscientiousness were similar to those found in other studies of personality: Genetic influence was substantial and there was little evidence of shared rearing environment. Results for Agreeableness were different: Genetic influence accounted for only 12% of the variance and shared rearing environment accounted for 21% of the variance. Few significant gender or age differences for genetic and environmental parameters were found in model-fitting analyses. PMID- 8345446 TI - Inhibitory effect of melatonin on platelet activation induced by collagen and arachidonic acid. AB - Melatonin, an indolamine synthesized in the pineal gland, is known to have antiprostanoid activity. The inhibition of platelet aggregation induced by melatonin has been proposed to take place through the cyclooxygenase pathway. In the present study, we found that melatonin has a marked inhibitory effect on collagen, arachidonic acid (AA), adenosine diphosphate (ADP), epinephrine, and A23187-induced aggregation in platelet-rich plasma. On the other hand, using metrizamide-filtered platelets resuspended in Tyrode's buffer, melatonin fails to suppress AA-induced platelet aggregation and 14C-5-HT release. Under the same conditions, melatonin inhibits collagen-induced platelet activation; however, the addition of threshold doses of AA (0.3 mM) abrogates this effect. These studies suggest that melatonin also inhibits platelet function at a stage preceding the cyclooxygenase-dependent pathway. PMID- 8345447 TI - The circadian nature of melatonin secretion in Japanese quail (Coturnix coturnix japonica). AB - Plasma melatonin concentrations were measured in Japanese quail held under different photoperiods and constant darkness (< 1 lux). When subjected to LD6:18 (6 hr light: 18 hr darkness), levels rose approximately 2 hr after lights-off, attained a peak level 8 hr after lights off, and subsequently declined to low daytime levels before the next lights-on signal. This generated a distinct daily rhythm in melatonin secretion with a duration of approximately 13 h. On exposing quail to a range of photoperiods, containing 6, 9, 11, 12, 13, 15, 18, or 20 hr of light per day, the onset of melatonin secretion remained essentially similar with the rise occurring soon after lights-off. However, the offset of melatonin secretion was suppressed by the light of the next day and thus a much truncated rhythm was produced under long (> 12 hr) photoperiods. Importantly, between night lengths of 4 to 18 hr (i.e., LD 20:4 to LD 6:18) a linear relationship existed between the duration of night-length and secretion of melatonin with the duration increasing by about 0.8 hr for each additional hour of darkness. If quail were released into darkness following a short (LD 6:18) or long (LD 20:4) day schedule, the rhythm persisted for at least two cycles with peaks occurring at about 24 hr intervals. In those quail coming into darkness from long days (LD 20:4), the rhythm of melatonin secretion decompressed rapidly on both sides of the peak, indicating that both the onset and offset of melatonin secretion were suppressed under long days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345448 TI - Junk science v. American competitiveness. PMID- 8345449 TI - Cardiovascular devices for the 1990s. PMID- 8345450 TI - Biological interactions: causes for risks and failures of biomaterials and devices. AB - Biomaterials and devices have been used in a variety of applications ranging from disposable extracorporeal devices and soft and hard tissue augmentation, to total artificial internal organs. However, there are risks and failures in each application which are a result of undesirable biological interactions. This article deals with various biological interactions in each category of implants and devices used in medical applications. PMID- 8345451 TI - Bacterial adhesion to protein-coated hydrogels. AB - Extended wear soft contact lenses have been implicated in the increased occurrence of corneal bacterial infections. This research investigated the effects of polymer chemistry, water content, and pre-sorbed proteins upon the adherence of Pseudomonas aeruginosa to model hydrogels with chemistries similar to those of extended wear soft contact lenses. The hydrogels were exposed to washed suspensions of P. aeruginosa in a laminar flow cell. Albumin, fibrinogen, desialylated fibrinogen, or mucin were deposited on the hydrogels before exposure to the bacteria. Results showed that with or without protein pre-exposure, bacterial adhesion decreased as water content increased. In the presence of the sorbed protein, the number of adherent bacteria increased by about 45%, and all four proteins caused similar increases in adhesion. Bacterial adhesion was not significantly influenced by the presence of sialic acid residues in the pre sorbed protein. PMID- 8345452 TI - Paracrine factors relevant to the regulation of spermatogenesis--a review. PMID- 8345453 TI - Effect of oestradiol on oxytocin-stimulated prostaglandin F2 alpha release in mares. AB - The objective of this study was to clarify the role of oestradiol in luteal function by examining its effect on the oxytocin stimulation of 15-keto-13,14 dihydro-prostaglandin F2 alpha (PGFM) concentrations in cyclic mares. In the first experiment, three groups of mares (4 per group) were given a bolus injection of 17 alpha-oestradiol (1 mg), oestradiol (1 mg) or vehicle on days 7, 9, 11, 13 and 15 of the cycle. Six hours later the mares were challenged with 10 iu oxytocin intravenously and frequent blood samples were taken from 15 min before to 15 min after for measurement of PGFM. Results showed a significant stimulatory effect of oestradiol (five times greater than controls at day 11; P < 0.05), but not of 17 alpha-oestradiol, on the oxytocin stimulation of PGFM. As a relatively large dose was given systemically in this experiment, a second experiment was performed to introduce a dose that was more physiological into the uterus. Small Silastic spheres (1 cm diameter) were impregnated with or without oestradiol at a concentration that gave a release rate similar to that of embryos at day 12 (10 ng h-1). These were inserted (one per mare) into the uterus of two groups of mares (five per group) on day 7. The mares were challenged with oxytocin on days 9, 11, 13 and 15 of the cycle and blood samples were taken as before for determination of PGFM. The results showed that oestradiol enhanced (four times greater than controls at day 13; P < 0.05) the oxytocin stimulation of PGFM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345454 TI - Effects of suppressing plasma FSH on ovarian follicular dominance in cattle. AB - The importance of FSH during development of the dominant follicle of the first wave of follicular growth in cattle was assessed by injecting heifers twice daily with 20 ml saline (n = 6) or 20 ml charcoal-extracted bovine follicular fluid (bFF; n = 10), containing inhibin, on days 6 and 7 of the oestrous cycle. All animals received a luteolytic dose of PGF2 alpha on day 8. The interval to oestrus after PGF2 alpha in controls was 2.6 +/- 0.2 days. Five of ten bFF treated heifers exhibited oestrus at the same time as controls (2.7 +/- 0.1 days), whereas time to oestrus in the remaining five bFF-treated heifers was significantly longer (6.8 +/- 0.6 days; P < 0.05). Treatment with bFF suppressed plasma FSH during the 48 h injection period (P < 0.05). Concentrations of FSH were not different in bFF-treated animals that did not display delayed oestrus compared with those in animals that exhibited delayed oestrus. In controls, the dominant follicle of the first wave continued growing during treatment and ovulated after injection of PGF2 alpha. In all ten bFF-treated animals, growth of the dominant follicle of the first wave was arrested during the treatment period. In bFF-treated animals that did not exhibit delayed oestrus, the dominant follicle resumed growth after luteolysis and ovulated. In bFF-treated animals that displayed delayed oestrus, the dominant follicle regressed after luteolysis and the ovulatory follicle was selected from a newly recruited (second) wave of follicular growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345455 TI - Effect of photoperiod on the annual cycle of testis growth in a tropical mammal, the little red flying fox, Pteropus scapulatus. AB - Little red flying foxes (Pteropus scapulatus) are seasonal breeders: they mate in late spring/early summer, and young are born the following autumn. In captivity, males housed outdoors in a normal breeding colony in natural daylight showed a single cycle of testis growth and regression each year. During reproductive quiescence, testicular volume was approximately 2 cm3; recrudescence began soon after the winter solstice; testicular volume was maximum at approximately 6.5 cm3 at the spring equinox; and regression was complete by the end of summer. To test whether photoperiod entrains or synchronizes the cycle, groups of males were housed indoors, without females, at constant temperature, and artificial lighting was timed to either mimic naturally changing daylength or provide alternating 3 month periods of short (11 h light:13 h dark) or long (16 h light:8 h dark) days (two groups, three months out of phase with each other). During 18 months, the applied photoperiod protocol had no effect on the frequency of testicular cycles (which remained at one per year), the time course of recrudescence and regression (as described above for normal outdoor control males), or the completeness of growth and regression stages. These results suggest that male P. scapulatus are not reproductively photoresponsive. PMID- 8345456 TI - Partial characterization of galactosyltransferase in human seminal plasma and its distribution in the human epididymis. AB - Galactosyltransferase activity has been partially characterized in human seminal plasma. Km values of 130 mumol l-1 for UDP-galactose and 2.25 mmol l-1 for N acetylglucosamine were calculated and the enzyme was found to be dependent on temperature and manganese and present as a highly active component of human seminal plasma. Galactosyltransferase was inhibited by nucleotides, glycosylated nucleotides, bovine and human alpha-lactalbumin but not by monosaccharides. Radiation inactivation studies revealed that the biologically active unit of seminal plasma galactosyltransferase has a molecular mass of 45 kDa. Although the majority of galactosyltransferase activity found in seminal plasma is probably of prostatic origin, we report for the first time that it is also present in human epididymal intraluminal fluid. Low activity was detected in the proximal caput region but activity increased to maximum values in the adjacent downstream segment, the intermediate caput region. Specific activity was relatively constant albeit at a lower value in the following epididymal segments and vas deferens. The significance of the epididymal and seminal plasma galactosyltransferase activities is unknown, but the enzyme could be implicated in glycosylation events that are known to be important in gamete interaction. PMID- 8345457 TI - Cryopreservation of expanded mouse blastocysts by vitrification in ethylene glycol-based solutions. AB - Experiments were conducted to find optimal conditions for obtaining high survival of expanded mouse blastocysts after vitrification. The vitrification solutions used were designated EFS20, EFS30 and EFS40, and contained 20%, 30% and 40% ethylene glycol, respectively, diluted in PB1 medium containing 30% Ficoll plus 0.5 mol sucrose l-1. In the toxicity test of the solutions and each cryoprotectant, ethylene glycol was found to be toxic to embryos. For vitrification, expanded blastocysts were exposed to the vitrification solutions at 10, 20 or 25 degrees C for various periods; they were then cooled rapidly in liquid nitrogen, after which they were warmed rapidly. When the embryos were directly exposed to EFS40 at 20 degrees C for 2 min before vitrification, 66% of them re-expanded during 48 h of post-warming culture. The re-expansion rates decreased when exposure time was shortened (0.5 min), when exposure temperature was lowered (10 degrees C), or when embryos were vitrified in EFS20 and EFS30, although these conditions should be less toxic. When embryos had been pretreated in a dilute (10-20%) ethylene glycol solution for 5 min, followed by short exposure (0.5 min) to EFS40 at 20 degrees C, post-vitrification survival rate increased to 83-84%; furthermore, the rate reached 94% when the temperature was increased to 25 degrees C. Expanded blastocysts cryopreserved by this two-step method developed into live young as well as control embryos after transfer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345458 TI - Follicular fluid composition in the grey seal (Halichoerus grypus) during the oestrous cycle. AB - During the period of lactational oestrus, the corpus luteum of ovaries of grey seals decreased in size following the birth of the pup, while on the contralateral ovary one major large follicle rapidly expanded. These large follicles had the highest concentration of oestradiol (4282 +/- 609 ng ml-1) and progesterone (499 +/- 168 ng ml-1). Osmolality (322 +/- 3 mosmol kg-1) and the intrafollicular concentration of electrolytes (Na: 126 +/- 1; Cl: 96 +/- 1; Ca: 1.3 +/- 0.1 mumol ml-1) and proteins (94 +/- 1 mg ml-1) were independent of stage of lactation and follicle size. Concentrations were lower in follicular fluid than in plasma. The concentrations of triglycerides and, to some extent, those of vitamin E, cholesterol and phospholipids were affected by the decrease in the plasma concentration of these components with the onset of lactation and the increase in follicle size. These two events resulted in a marked decrease of these components in the largest follicles at the end of lactational oestrus. Vitamin A (exclusively as retinol), although a blood-borne component in follicular fluid, was the only component with a higher concentration in small and medium follicles than in plasma and decreased with increasing follicle size despite an increase in plasma retinol. This decrease and the negative correlation with intrafollicular oestradiol might indicate a high demand of preovulatory follicle structures for vitamin A owing to its possible importance in steroid hormone or protein synthesis or in both processes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345459 TI - Stimulation of collagen secretion by relaxin and effect of oestrogen on relaxin binding in uterine cervical cells of pigs. AB - The role of relaxin and oestrogen in the remodelling of connective tissue was investigated by testing collagenase-dispersed cells (3 x 10(5) cells per well) from the uterine cervix of gilts for relaxin binding and collagen secretion. Relaxin-binding sites on these cells were quantified by specific binding of a saturating dose of 125I-labelled monotyrosyl relaxin at optimal conditions. Oestrogen at doses from 0.4 to 50 ng ml-1 increased relaxin binding in a time- and dose-dependent manner. Scatchard plot analysis exhibited curvilinearity, which suggested two classes of relaxin-binding sites. The addition of relaxin (0, 100, 500 ng ml-1) alone (P < 0.05) or in combination with oestrogen (oestradiol benzoate: 0, 50, 250 ng ml-1) increased protein secretion into the culture medium. Hydroxyproline concentration (as an index of collagen) in the medium was increased (P < 0.05) only in the presence of both relaxin and oestrogen. Actinomycin D (500 ng ml-1) and cycloheximide (500 ng ml-1) inhibited hydroxyproline secretion induced by combined relaxin and oestrogen treatment. Dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cAMP: 0, 0.1, 1.0, 5.0 mmol l-1) was a potent stimulator of hydroxyproline secretion. These results indicate that relaxin, probably via a cAMP pathway, stimulates hydroxyproline secretion in the presence of oestrogen through a protein- and RNA-synthesis dependent process. Oestrogen plays a role in augmenting the sensitivity of uterine cervical cells to relaxin in the pig. PMID- 8345460 TI - GnRH in the male dog: dose-response relationships with LH and testosterone. AB - Dose-response relationships between GnRH and LH, and between GnRH and testosterone, were investigated in six male dogs by intravenous administration of a GnRH analogue at different doses. Each dose of GnRH analogue induced an immediate rise in the plasma concentration of LH and then a rise in plasma testosterone concentration. Irrespective of the dose used, the rise in testosterone began 10 min after the GnRH injection. Administration of GnRH at doses of 0.01, 0.1, 1, 10 and 100 micrograms kg-1 resulted in maximum LH concentrations in plasma (mean +/- SEM; n = 6) of 22 +/- 7, 27 +/- 6, 40 +/- 7, 57 +/- 13 and 56 +/- 10 micrograms l-1, respectively. These doses induced maximum concentrations of testosterone in plasma (mean +/- SEM; n = 6) of 16 +/- 4, 20 +/ 4, 22 +/- 3, 22 +/- 4 and 24 +/- 7 nmol l-1, respectively. The lag time between peak concentrations of LH and testosterone varied from 35 to 55 min. The calculated maximum response of testosterone to LH, secreted by the anterior pituitary after GnRH injection, was 1.8 times higher than to GnRH. It was concluded that intravenous administration of GnRH induced marked and dose dependent increases in plasma concentrations of LH and testosterone, and that there does not appear to be a direct effect of GnRH on Leydig cells in male dogs. PMID- 8345461 TI - Culture of rabbit zygotes into blastocysts in protein-free medium with one to twenty per cent oxygen. AB - Embryos were collected from superovulated Dutch rabbits 19 h after injection of LH and insemination. The embryos were at the one-cell stage at that time and those judged to be normal by the absence of granular cytoplasm and regular shape were distributed randomly within donors into culture dishes containing 500 microliters of a macromolecule-free medium consisting of RPMI-1640 and low glucose Dulbecco's modified Eagle's medium, 1:1, without a cover of oil. In Expt 1, O2 concentrations of 5, 10 and 15%, with 5% CO2 plus 90, 85 and 80% N2, respectively, were tested. In Expt 2, O2 concentrations of 1, 5 and 20% were combined with 5% CO2 and the remaining gas was N2. After 84 h in culture at 39 degrees C, embryos were examined for stage of development and stained with Hoechst 33342 so that the number of cells could be counted. In Expt 1, the proportion of embryos reaching the hatching blastocyst stage after 84 h in culture in 5, 10 and 15% O2 was 48, 38 and 21%, (P < 0.01) and the cell number per embryo averaged 258, 226 and 188, respectively (P < 0.01). In Expt 2, the proportion of hatching embryos after 84 h in culture in 1, 5 and 20% O2 was 67, 72 and 29% (P < 0.01), respectively. Cell numbers in the 1 and 5% O2 concentrations were higher than in the 20% O2 concentration (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345462 TI - Glucose and pyruvate metabolism in preimplantation blastocysts from normal and diabetic rats. AB - Glucose metabolism was analysed in day-5 rat blastocysts incubated in the presence of [5-3H]-, [6-14C]- or [U-14C]glucose. Glycolysis, quantified by 3H2O recovery rate, was the main pathway of glucose utilization by fresh (11.5 +/- 0.36 pmol per embryo h-1) or cultured (24 h) blastocysts (20.4 +/- 0.6 pmol per embryo h-1). Glucose consumption rate was almost saturated at a medium glucose concentration of 0.28 mmol l-1 (Km: 0.17 mmol l-1; Vmax: 23 pmol per embryo h-1). A further 10% increase in glucose utilization was obtained with a tenfold higher glucose concentration (3 mmol l-1). Phloretin completely abolished the rapid component of glucose utilization kinetics, suggesting the existence of a Na(+) independent glucose transport system. Less than 1% of [6-14C]glucose consumed by cultured blastocysts was oxidized through the Krebs cycle. [1-14C]pyruvate, however, was oxidized at a rate of 2 pmol per embryo h-1 by fresh blastocysts. The pentose-phosphate pathway accounted for about 2% of glucose utilization. One to two per cent of the total glucose metabolized in 24 h was retained in macromolecules. Insulin had no effect on glucose uptake, utilization, incorporation and turnover, or on pyruvate oxidation. Blastocysts from diabetic mothers utilized glucose at a rate similar to that of normal blastocysts. These results show that glucose is actively taken up by rat blastocysts and utilized mainly through the Embden-Meyerhof pathway, which is rapidly saturated at low glucose concentrations. Retention of glucose-derived products in macromolecules, although relatively small, may modulate the effect of high glucose concentrations on embryo growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345463 TI - Effects of the duration of exposure to hormone supplements on cytoplasmic maturation of pig oocytes in vitro. AB - The effect of hormone supplements on cytoplasmic maturation in vitro was examined by incubating oocyte-cumulus complexes, in a medium with PMSG (10 iu ml-1), hCG (10 iu ml-1) and oestradiol (1 microgram ml-1) for various periods and then transferring them to medium without added hormones for the remainder of the maturation period. Exposure of oocyte-cumulus complexes to hormone supplements for 2 h improved only germinal vesicle breakdown and maturation rates compared with complexes not exposed to added hormones. The removal of hormone supplements at 20 h after the start of culture enhanced the ability of oocytes to form male pronuclei 10 to 12 h after insemination. Further, the effects of transfer of intact and oocytectomized oocyte-cumulus complexes to hormone-free medium at 20 h on cumulus expansion were examined. The diameter and morphology of the intact oocyte-cumulus complexes were improved after the removal of oocyte-cumulus cell complexes from hormonal exposure. The responses of oocytectomized oocyte-cumulus complexes to hormone were similar to those of intact oocyte-cumulus complexes with the exception of corona radiata expansion. The results suggest that the removal of hormone supplements from maturation media at 20 h after culture enhanced cytoplasmic maturation and cumulus expansion. Further, cumulus expansion does not appear to depend on intercellular communication between cumulus cells and oocytes. Oocytectomy did influence expansion of the corona radiata during culture. PMID- 8345464 TI - Effects of alpha-amanitin on nuclear maturation of porcine oocytes in vitro. AB - The effects of alpha-amanitin on cumulus enclosed and denuded porcine oocytes exposed to this heterogeneous nuclear RNA (hnRNA) synthesis inhibitor at different times (0, 0.5, 1, 2, 4, 6, 8, 12 and 20 h) after the start of culture was investigated. A further objective was to determine the sequence of nuclear progression after removing the inhibitor. The addition of 10 micrograms alpha amanitin ml-1 to a gonadotrophin containing medium (10 iu PMSG ml-1 in TCM 199) at 0, 0.5 or 1 h after the onset of culture prevented cumulus expansion, and only 4.4, 6.4 and 3.5% of oocytes underwent germinal vesicle breakdown. This inhibitory effect was considerably reduced by delaying the addition of the drug to the culture medium for 2-8 h (2 h: 34.9%, 4 h: 53.5%, 6 h: 46.9%, 8 h: 59.2% germinal vesicle breakdown), and no inhibition of nuclear maturation was observed when alpha-amanitin was added after 12 or 20 h following explantation of the oocytes. When cumulus-oocyte complexes were cultured for > or = 2 h in inhibitor free medium and then transferred to medium supplemented with alpha-amanitin, full cumulus expansion was observed in all cases, at the end of the 44 h culture. Denudation of the oocytes before culture in either medium supplemented with alpha amanitin or microinjection of alpha-amanitin into the ooplasm at concentrations of 1.0 and 10.0 mg ml-1 remained without any effect on nuclear progression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345465 TI - Binding of lipid droplets and mitochondria to intermediate filaments in rat Leydig cells. AB - We have examined the distribution of lipid droplets and mitochondria in relation to the cytoskeletons of Leydig cells in primary culture by using light and electron microscopy on living, intact and detergent-extracted cells. After mild extraction with Triton X-100 lipid droplets and mitochondria retained their original distribution within the cell. Double immunofluorescent microscopy showed that both structures co-localise with intermediate filaments. Transmission electron microscopy of intact (unextracted) and mildly extracted Leydig cells showed that intermediate filaments are closely associated with mitochondria and lipid droplets. By examination of stereo pairs, intermediate filaments were shown to establish direct contact with mitochondria and lipid droplets. The association of droplets and mitochondria with intermediate filaments suggests possible mechanisms by which the transport of cholesterol takes place from droplets to mitochondria where this substrate enters the steroidogenic pathway. PMID- 8345466 TI - Characteristics of the oestrous cycle and duration of gestation in chital hinds (Axis axis). AB - Duration of oestrous cycle and gestation, and characteristics of postpartum oestrus of chital hinds are described. Mean duration of the oestrus cycle of chital hinds was 19.3 +/- 1.3 days, with a range of 17-21 days. Serum progesterone profiles are shown, with minimum progesterone concentrations near oestrus less than 2.7 nmol l-1, and maximum luteal values 16-26 nmol l-1. Mean duration of gestation was 234.5 +/- 3.0 days (n = 17). PMID- 8345467 TI - Localization and concentration of a new bioactive acetic seminal fluid protein (aSFP) in bulls (Bos taurus). AB - The concentration of the new bioactive acetic seminal fluid protein (aSFP) was determined in body fluids of bulls. An aSFP-specific radioimmunoassay was elaborated and established for routine measurement. No crossreaction of the aSFP antibody was found with other seminal plasma proteins and known growth factors. The 14 kDa aSFP was detected in secretions of ampulla and seminal vesicles by immunoblot analysis, but not in testis, epididymis or blood. Large quantities of aSFP were measured by radioimmunoassay in the fluid from the ampulla (2.6 +/- 0.3 mg ml-1) and seminal vesicles (3.0 +/- 0.4 mg ml-1). Immunohistochemistry techniques demonstrated that aSFP was localized mainly in the secretory epithelium of ampulla and seminal vesicles. Large amounts of aSFP (4.0 +/- 0.4 mg ml-1) were present in seminal plasma of bulls within a range of 1-7 mg ml-1, but aSFP could not be found on membranes of spermatozoa. Concentrations vary considerably among individuals, suggesting that aSFP may have a role in bovine reproduction. PMID- 8345468 TI - Effect of exposure to a boar on circulating concentrations of LH, FSH, cortisol and oestradiol in prepubertal gilts. AB - Serum concentrations of LH, FSH, oestradiol and cortisol were measured in control gilts not exposed to a boar and in gilts with fence-line exposure to a boar that allowed full muzzle contact. All gilts were between 134 and 200 days of age. Control gilts showed first oestrus at 193 +/- 7 days of age (n = 5). Twelve of the gilts exposed to the boar showed first oestrus at 169 +/- 5 days of age and five had not shown oestrus by 200 days of age. Introduction of a boar produced a transient increase in LH pulse frequency lasting no longer than 20 days (P < 0.001) in gilts responding to the boar with oestrus. Basal and mean serum LH concentrations were also increased (P < 0.05) in the gilts that responded to a boar with oestrus, but only in the 6 h after introducing the boar. Mean serum concentrations of FSH were lower in gilts exposed to a boar compared with the controls at 10 days after introduction of the boar, but by 20 days only gilts responding to the boar with oestrus had lower FSH concentrations (P < 0.05). Serum concentrations of cortisol decreased over the day the boar was introduced in all groups of gilts (P < 0.05) and were always highest in gilts exposed to a boar but not showing oestrus by 200 days of age (P < 0.05). There were no significant trends in serum concentrations of oestradiol but oestradiol concentrations varied over a wide range in gilts that did not respond to the boar with oestrus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345470 TI - Relationship between iron-catalysed lipid peroxidation potential and human sperm function. AB - The relationship between lipid peroxidation and the functional competence of human spermatozoa has been investigated in a cohort of 31 infertility patients. Lipid peroxidation was assessed using a sensitive fluorometric assay for the generation of malondialdehyde in response to the presence of a ferrous ion promoter. Sperm function was evaluated by monitoring the movement characteristics of these cells and their capacity for sperm-oocyte fusion. Each sample was separated into high- and low-density sperm populations on discontinuous, two-step (40%:80%), Percoll gradients prior to analysis. The way in which individual ejaculates fractionated on these gradients was highly positively correlated (P < 0.001) with the lipoperoxidation status of the spermatozoa; the greater the potential for malondialdehyde generation, the higher the proportion of cells entering the low density region of the gradients. The lipoperoxidation potential of the freshly prepared spermatozoa was also highly predictive (P = 0.0001) of their capacity for movement at 3 and 24 h and their ability to exhibit sperm oocyte fusion in response to the ionophore A23187. The potential for malondialdehyde generation in the 40% and 80% Percoll fractions was positively associated with midpiece abnormalities in the spermatozoa. These results emphasize the importance of lipid peroxidation in the pathophysiology of male infertility and suggest a mechanism by which such damage might arise. PMID- 8345469 TI - Identification of endothelin-1, endothelin-2 and endothelin-3 in human endometrium. AB - This study determined the presence of specific endothelin isoforms in human endometrium using high performance liquid chromatography (HPLC) combined with radioimmunoassay, and immunocytochemistry to detect the endothelin precursors (proendothelin-1, proendothelin-2 and proendothelin-3). Endothelin-like immunoreactivity was measured in HPLC eluates using antisera raised in rabbits against the carboxy-terminal heptapeptide of endothelin-1, which is common to the three endothelin isoforms. Of eight endometrial samples analysed by HPLC, three were in the proliferative phase of the cycle, and five in the secretory phase. Endothelin-1 was detected in seven samples, whereas endothelin-2 and endothelin-3 were seen in four and five specimens, respectively. No relationship was seen between endothelin isoforms and the stage of the cycle. Immunocytochemistry was performed on five proliferative and three secretory phase tissues. When present, staining for the precursor proendothelins was localized to endometrial glandular and luminal epithelium (proendothelin-1, 5 of 8; proendothelin-2, 5 of 8; proendothelin-3, 6 of 8). In two sections, staining was also seen in vascular endothelium using antibody raised against proendothelin-1 (n = 1) and proendothelin-3 (n = 1). These data provide evidence that the three endothelin isoforms are present in human endometrium, and suggest that these potent vasoactive agents may play a role in the paracrine control of the uterine vascular bed. PMID- 8345471 TI - In vitro fertilization and embryo culture in the grey short-tailed opossum, Monodelphis domestica. AB - In vitro fertilization and early embryo culture was undertaken in the South American marsupial, the grey short-tailed opossum, Monodelphis domestica. Adult females were induced into oestrus by a system of pairing with an unfamiliar male and mature oocytes were recovered from the ovary 15-18 h after mating and placed in pre-warmed modified MEM medium at 33 degrees C (basal body temperature) or 37 degrees C. Spermatozoa recovered from the cauda epididymides of adult males were preincubated in medium for 2 h during which time paired spermatozoa separated and initiated hyperactivated motility. Oocytes were transferred to 0.4 ml drops of spermatozoa containing 0.5-1.0 x 10(6) spermatozoa ml-1. Only single spermatozoa bound to the zona pellucida, and fertilization occurred within 1-2 h as indicated by a breach in the zona and confirmed by electron microscopy. At 37 degrees C, 95 of 152 (62.5%) oocytes were fertilized and 64 (67%) developed to two-cell stage or beyond. At 33 degrees C, 5 of 28 (18%) oocytes were fertilized. This is the first report of complete in vitro fertilization in a marsupial. PMID- 8345472 TI - Possible roles for prostaglandins E2 and F2 alpha in seasonal changes in ovarian steroidogenesis in the frog (Rana esculenta). AB - Concentrations of PGE2, PGF2 alpha, androgens and oestradiol in plasma, and ovary weights were measured in the female frog, Rana esculenta, during the annual breeding cycle. Experiments were carried out in vivo to study the effects of PGE2 and PGF2 alpha on plasma sex steroids during the following stages: pre reproduction (April), reproduction (May), post-reproduction (June) and recovery (October). Experiments were performed in vitro during these stages to evaluate the effects of these two prostaglandins on the secretion of ovarian steroids. Concentrations of PGE2 were low in plasma during winter hibernation, the reproduction and post-reproduction stages, whereas they were high during the pre reproduction and recovery stages. PGE2 treatment in vivo increased androgen secretion in April, whereas PGF2 alpha treatment increased oestradiol secretion in June and October. In experiments in vitro, PGE2 increased androgen secretion and decreased oestradiol secretion from ovaries collected in April, whereas PGF2 alpha increased oestradiol secretion from ovaries collected in October. These results suggest that a seasonal increase in plasma PGE2 may inhibit breeding activity, probably by stimulating ovarian androgen secretion, whereas, as previously reported, a seasonal increase in plasma PGF2 alpha may inhibit breeding, by stimulating ovarian oestradiol secretion. PMID- 8345473 TI - Cellular dynamics of growth in sheep and goat synepitheliochorial placentomes: an autoradiographic study. AB - This paper demonstrates that in sheep and goats the two definitive fetomaternal interface layers are developmentally related. The fetal trophectoderm consists of binucleate and uninucleate cells. The apical microvilli of the trophectoderm interdigitate with a layer consisting of syncytial plaques of limited area bounding the maternal connective tissue. Our previous histological ultrastructural and immunocytochemical work has indicated that throughout pregnancy the fetal binucleate cells migrate to and fuse with the uterine epithelium or its derivatives to form these syncytial plaques which constitute a persistent fetomaternal tissue unique to ruminants. This quantitative autoradiographic study of thymidine incorporation into sheep and goat placentas confirms the central role of the binucleate cell in placental growth, demonstrates that throughout pregnancy all binucleate cells migrate and indicates that most of the nuclei of the syncytial plaques, which appear to have a limited lifespan, derive from binucleate cell fusion. PMID- 8345474 TI - Concentrations of faecal immunoreactive progestagen metabolites during the oestrous cycle and pregnancy in the black rhinoceros (Diceros bicornis michaeli). AB - The analysis of reproductive hormones in faecal samples is a possibility for non invasive monitoring of reproductive status in free-ranging or intractable species. In the present study, faecal samples from three black rhinoceroses (Diceros bicornis michaeli) were collected at about weekly intervals during oestrous cycles and pregnancy. Daily samples were taken during the week after parturition. Total immunoreactive progestagens in faecal extracts were analysed with three different enzymeimmunoassays (EIA) that had considerable specificity for progestagens containing either a 20 alpha-hydroxyl or a 20-keto group. With each EIA it was possible to distinguish between the follicular and luteal phases of the oestrous cycle. Mating corresponded with low concentrations of faecal progestagens. Samples from five and six consecutive cycles were available from two rhinoceroses and cycle lengths of 24 and 26.5 days were calculated. All three animals became pregnant and the duration of gestation ranged from 440 to 470 days. After fertilization, the concentration of progestagens increased continuously, as in the luteal phase, reaching values 5-10 times higher between days 60 and 250. During the two weeks before parturition faecal progestagens declined and within 3-4 days post partum had reached follicular phase values. It was concluded that several immunoreactive progestagens are present in the faeces of black rhinoceroses and that their measurement with EIA enables non-invasive monitoring of the oestrous cycle and pregnancy. PMID- 8345475 TI - Maturational changes in gonadotrophin secretion: the LH response to realimentation and a nocturnal increment in LH secretion of feed-restricted prepubertal gilts. AB - Potential maturational changes in patterns of LH secretion during feed restriction and the LH response to realimentation were examined. Ten sets of four growth-matched littermate gilts were fed ad libitum, to reach either 55, 65, 75 or 85 kg target body weights (one littermate per weight). Gilts were then maintenance fed for 8 days (days 1-8), and to appetite on day 9, and kept in a 9 h light (07:00-16:00 h):15 h dark photoperiod. Blood samples were obtained every 10 min from 07:00 to 16:00 h, and from 16:00 to 24:00 h on day 8 to evaluate any nocturnal rise in LH, and from 07:00 to 16:00 h on day 9 to evaluate the LH response to realimentation. Radioimmunoassays for LH, FSH, melatonin and oestradiol were performed on selected plasma samples. In all three sampling periods, LH and FSH secretion decreased as gilt weight increased, in a quadratic manner. During feed restriction, daytime LH, but not FSH, secretion was lower than at nighttime, irrespective of weight. Daytime LH secretion increased in response to realimentation, irrespective of weight. Plasma oestradiol concentrations were increased by feed restriction and decreased by realimentation but showed little relationship to gilt weight. No consistent relationship was established between plasma melatonin concentrations and ambient illumination. In conclusion, LH secretion exhibits a diurnal rhythm during feed restriction in the prepubertal gilt and, in a similar way to FSH, decreases as puberty is approached. The plane of nutrition influences circulating oestrogen concentrations. The increase of LH secretion following realimentation is not influenced by maturation over the prepubertal period. PMID- 8345476 TI - Effects of onapristone, tamoxifen and ICI 182780 on uterine prostaglandin production and luteal function in nonpregnant guinea-pigs. AB - Onapristone (a progesterone antagonist) or ICI 182780 (an oestrogen antagonist) administered to guinea-pigs on days 11-14 of the cycle significantly reduced uterine PGF2 alpha output on day 15. Concentrations of progesterone in plasma of onapristone-treated and ICI 182780-treated guinea-pigs were still high on day 15 indicating that luteal regression had been prevented. These findings indicate that progesterone and oestradiol are necessary for increased PGF2 alpha production by the uterus towards the end of the cycle, and support the hypothesis that oestradiol acting on a progesterone-primed uterus is the physiological stimulus for increased uterine PGF2 alpha synthesis and release in guinea-pigs. The capacity of the endometrium to synthesize PGF2 alpha on day 15 was reduced by treatment with ICI 182780 and, unexpectedly, by treatment with onapristone, indicating that onapristone may also be antagonizing the release or action of oestradiol in some way. Tamoxifen was an agonist in guinea-pigs since it induced vaginal opening. It had no inhibitory effect on uterine PGF2 alpha output and did not delay luteal regression when administered between days 11 and 14 of the cycle. However, it redirected PG synthesis in homogenates of endometrium and myometrium from PGI2 (as indicated by 6-keto-PGF1 alpha) to PGF2 alpha. The output of 6-keto-PGF1 alpha from the uterus of day 15 guinea-pigs was reduced following tamoxifen treatment, but the high output of PGF2 alpha from the uterus was not affected. PMID- 8345477 TI - Changes in adenylyl cyclase activity in human endometrium during the menstrual cycle and in human decidua during pregnancy. AB - Adenylyl cyclase activity was studied in human endometrium during the menstrual cycle and in human decidua during pregnancy. Higher adenylyl cyclase activity was found in the endometrium than in the myometrium, corpus luteum or Fallopian tubes. In the endometrium, the basal and stimulated activities were highest in the fundus and decreased slightly from the fundus to the isthmus. Prostaglandin stimulated adenylyl cyclase activity increased gradually from the proliferative phase to the secretory phase, and then quickly reached its highest value in the late secretory phase. Catecholamine-stimulated adenylyl cyclase activity reached a peak in the late proliferative phase and decreased significantly thereafter. Forskolin-stimulated activity was significantly higher throughout the secretory phase than in the proliferative phase. In the decidua, prostaglandin-, catecholamine- and forskolin-stimulated adenylyl cyclase activities in late pregnancy were significantly lower than those in early pregnancy. Our results demonstrate dramatic alterations in adenylyl cyclase activity in human endometrium during the menstrual cycle and in human decidua during pregnancy. PMID- 8345478 TI - Effects of the Booroola gene (FecB) on body weight, ovarian development and hormone concentrations during fetal life. AB - The aim of this study was to determine whether the FecB gene influenced some aspects of fetal development in sheep. Carrier (BB/B+) and non-carrier (++) female fetuses were recovered at specific times of gestation, namely, days 40, 55, 75, 90, 95 and 135. The results showed that the FecB gene influenced litter size, body weight and ovarian development during fetal life. The mean litter sizes were larger (P < 0.05) and body weights were lighter (P < 0.05) at most gestational ages in BB/B+ than in ++ fetuses. Morphometric studies of the ovary showed that the development of the BB/B+ ovaries was retarded: the ++ genotype had more oogonia at day 40 (P < 0.01), more germ cells entering meiosis at day 55, more primordial follicles developing at days 75, 90 and 95 (P < 0.05), a greater loss of germ cells by atresia at day 90 (P < 0.01) and more growing follicles (P < 0.01) and more antral follicles (P < 0.05) at day 135. Differences between the BB/B+ and ++ genotypes in the plasma concentrations of immunoreactive (i) inhibin, i-FSH, bioactive (b)-FSH or (i)-LH were not apparent at any age except for i-LH at day 75 (BB/B+ > ++; P < 0.05). Likewise no differences were noted in the contents of ovarian or adrenal oestradiol or i-inhibin except for i inhibin in the adrenal at day 75 (++ > BB/B+, P < 0.01). No differences between the genotypes were noted in the i-inhibin contents of the mesonephros at day 40. In mid- to late but not early gestation (i.e. days 40 and 55) significant correlations (i.e. P < 0.05) were noted between litter size and body weight at days 75, 90 and 135, and between litter size and ovary weight, ovary volume, adrenal weight and pituitary weight at day 135. To eliminate the effect of litter size, equal numbers of BB/B+ and ++ embryos were transferred to respective recipient ewes, and fetuses were recovered at the equivalent of days 40 and 90 of gestation. The results showed that the genotypic difference in fetal body weight at day 40 (++ > BB, P < 0.001) and in number of oogonia at day 90 (++ > BB/B+, P < 0.05) were independent of litter size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345479 TI - Effects of fetal genotype and uterine environment on placental development in equids. AB - Measurement of the concentrations of equine chorionic gonadotrophin (eCG) in the serum of pregnant mares and Jenny donkeys carrying normal intraspecies and hybrid interspecies pregnancies suggested that the production of this hormone may be influenced by parental gene imprinting. Specifically, a differential expression of maternal and paternal genes may control the size and secretory activity of the structures that secrete eCG, the fetal endometrial cups. However, bisection of an interspecies mule embryo followed by transfer of the resulting demi-embryos and other intact mule embryos to horse and donkey recipients resulted in striking differences in the size, secretory activity and lifespan of the endometrial cups in two types of surrogate mother. This finding has therefore demonstrated the ability of uterine factors to alter profoundly the development and characteristic phenotype of the specialized invasive chorionic girdle portion of the equine trophoblast that gives rise to the endometrial cups. PMID- 8345480 TI - Role of platelet-derived growth factor in development of in vitro matured and in vitro fertilized bovine embryos. AB - This experiment was designed to determine whether the stimulatory effects of bovine oviductal epithelial cells (BOEC) on development of early bovine embryos are due to platelet-derived growth factor (PDGF). Four hundred and twenty five 8 cell bovine embryos derived from in vitro maturation and in vitro fertilization procedures were equally and randomly allotted to one of the following culture treatment groups: control medium alone (Menezo's B2 medium; MB2), MB2 with 1 ng PDGF ml-1 (PDGF), 1 ng PDGF ml-1 and 10 micrograms anti-PDGF antibody ml-1 (PDGF + Ab), BOEC or BOEC and 10 micrograms anti-PDGF antibody ml-1 (BOEC + Ab). All embryos were cultured in 100 microliters of serum-free MB2 medium supplemented with 2 mg fatty-acid-free bovine serum albumin ml-1. Embryos for all treatment groups were incubated at 39 degrees C and 5% CO2 in humidified air in groups of five embryos per well in 96-well culture plates until 7 days after in vitro insemination. A higher proportion of embryos developed to > 8-cell and to the morula stage following culture with PDGF, BOEC or BOEC+Ab than with MB2 alone. Incubation of PDGF and BOEC-treated embryos with anti-PDGF reduced development to the morula and blastocyst stages. However, anti-PDGF did not completely inhibit blastocyst development when added to BOEC. In addition, embryos incubated with BOEC and anti-PDGF contained a reduced number of inner cell mass cells compared with embryos incubated with BOEC alone. These results indicate that PDGF provides a developmental stimulus similar to BOEC for bovine embryos at the fourth cell cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345481 TI - Secretion of matrix metalloproteinases by human endometrial cells in vitro. AB - At each menstrual cycle, the uterine endometrium undergoes intense remodelling. Of the many factors implicated in tissue remodelling, the matrix metalloproteinases (MMPs) play a central role owing to their capacity to degrade the extracellular matrix. The aim of this study was to examine the nature and cellular origin of endometrial proteases as evaluated in culture systems with clearly characterized cell types. Endometrial cells from hysterectomy specimens were prepared using collagenase digestion. Bone-marrow-derived cells (a known source of proteases) were removed by immunopurification. Cells were cultured on different substrates (matrigel, agarose, glass or plastic). Purity of cell preparations was examined by immunocytochemistry, and proteases were characterized by zymography on SDS-PAGE containing gelatin. The cell phenotype in culture was largely influenced by the type of substrate. Gelatin-degrading enzymes detected in culture supernatants of stromal and epithelial cells had molecular masses ranging from 42 to 248 kDa, and were identified as metalloproteinases. We conclude that human endometrial stromal and epithelial cells express several matrix metalloproteinases, the expression of which clearly depended on the purity of cell preparation, on cell adhesion and on the nature of the substrate on which the cells grew. These enzymes might be involved in endometrium remodelling, blastocyst implantation and trophoblast invasion. PMID- 8345482 TI - Effects of induction of low plasma progesterone concentrations with a progesterone-releasing intravaginal device on follicular turnover and fertility in cattle. AB - The effects of concentration of progesterone in plasma on development and fertility of the first wave dominant follicle were studied in cattle. To identify a source of exogenous progesterone that would permit extension of the first wave dominant follicle, nonlactating Holstein cows (n = 6) received on day 8 of two successive oestrous cycles an injection of PGF2 alpha (25 mg) and a new (1.9 g of progesterone (Period 1)) or used (approximately 1.2 g of progesterone (Period 2)) CIDR-B device that was removed on day 17. Control cows (n = 6) received a new CIDR-B device on day 8 that was removed on day 17 and a PGF2 alpha injection (25 mg) on day 17. Ultrasonography and collection of blood samples were performed on alternate days throughout the experiment. Plasma concentrations of progesterone and oestradiol were different between treatments (P < 0.0001 and P < 0.05, respectively). The dominant follicle was maintained until day 17 and ovulated upon removal of the intravaginal device in 1 of 6, 6 of 6 and 0 of 6 in new CIDR B, used CIDR-B and control groups, respectively (P < 0.01). The preovulatory dominant follicles were 14.2 +/- 1.6 mm, 20 +/- 1.3 mm and 10 +/- 1.3 mm, respectively (P < 0.001) on day 17. There were fewer 5-9 mm follicles in cows having a persistent dominant follicle (P < 0.01). The interval to onset of oestrus was negatively correlated with size of the dominant follicle on day 17 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345483 TI - Influence of day of oestrus on egg viability and comparative efficiency of in vitro fertilization in domestic cats in natural or gonadotrophin-induced oestrus. AB - Thirty-six domestic cats received 100 iu hCG (i.m.) on day 1, 2 or 3 of a natural, behavioural oestrus. Twenty-two anoestrous cats were injected with 150 iu pregnant mares' serum gonadotrophin (PMSG; i.m.) followed 84 h later by 100 iu hCG. Twenty-four to 26 h after hCG, all cats were examined laparoscopically to determine the number of ovarian follicles and to recover follicular eggs. Mature eggs were cultured with conspecific spermatozoa and examined 30 h later for cleavage. Within the natural oestrus group, cats on day 1 produced fewer (P < 0.05) follicles and total eggs than females on day 2 or 3, and 88.9% of the day 1 eggs were degenerate or immature and unsuitable for in vitro fertilization (IVF). Although only 54.5% of the cats in the PMSG/hCG group exhibited overt oestrus, mean (+/- SEM) numbers of follicles (9.7 +/- 0.8) and oocytes recovered (8.7 +/- 0.8) were at least twofold greater (P < 0.001) than those measured in the natural oestrus group (3.7 +/- 0.6; 3.4 +/- 0.6, respectively) or subgroups on day 2 (3.7 +/- 0.4; 3.3 +/- 0.4) and day 3 (5.7 +/- 0.8; 5.3 +/- 0.8). Overall, the proportion of eggs cleaving in vitro was similar (P > 0.05) between the natural oestrus group (48.3%) and the PMSG/hCG group (50.9%), but the latter group produced more than twice the number of embryos per donor. Embryo quality was unaffected (P > 0.05) by day of hormone treatment, and more than 80% of all two cell embryos were rated good-to-excellent quality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345484 TI - Serum concentrations of oestradiol and progesterone and frequency of sexual behaviour during the normal oestrous cycle in the snow leopard (Panthera uncia). AB - Serum oestradiol and progesterone concentrations were measured at weekly intervals for six months, and correlated with daily behavioural observations in two adult female snow leopards (Panthera uncia). Three oestradiol peaks (> 21 pg ml-1; interval 3.6 weeks) were identified in a snow leopardess housed alone (two more were probably missed because of the weekly sampling schedule), and three oestradiol peaks were identified in a snow leopardess housed with a male as a breeding pair (interval 6 weeks). Daily frequencies of feline reproductive behaviour averaged 1.77 observations per observation period during weeks of high oestradiol and 0.62 during weeks of low oestradiol. Progesterone concentrations did not rise above baseline values (< 2 ng ml-1) in the isolated animal, but 6 weeks of high progesterone concentrations (4.9-38.8 ng ml-1) was recorded in the paired snow leopardess following mating. No offspring were produced. Snow leopards were observed daily for an additional 4.5 years. Sexual behaviour peaks could be clearly identified from December through April, and average daily sexual behaviour scores were higher during these months than during the rest of the year. Intervals between sexual behaviour peaks for the isolated snow leopardess averaged 3.03 weeks. The sexual behaviour of the paired snow leopards decreased for 8-9 weeks following mating when no offspring were produced, and decreased for 13 weeks in one year when a single cub was born. PMID- 8345485 TI - Gonadotrophin-releasing hormone and the control of ovulation rate by the FecB gene in Booroola ewes. AB - Booroola sheep carry a FecB gene that confers high fecundity. The aims of the present studies were to determine in homozygous carriers (BB) and non-carriers (++) of the Booroola FecB gene whether there are FecB differences in the secretory characteristics of GnRH in hypophyseal-portal blood of ovariectomized ewes (Expt 1) and whether differences in ovulation rate would occur following the administration of PMSG and pulsatile GnRH to ovary-intact Booroola ewes with hypothalamic-pituitary disconnection (HPD) (Expt 2). In Expt 1, no FecB gene specific differences were noted for GnRH with respect to pulse frequency, pulse amplitude or overall secretion rate. Irrespective of genotype there were 1.9 +/- 0.2 GnRH pulses h-1 (n = 20 ewes; 10 BB and 10 ++ animals) and 1.9 +/- 0.1 pulses of immunoreactive (i) LH h-1. In Expt 2, ovulation was induced in the HPD ovary intact animals on three occasions (e.g. 56, 393 and 423 days after HPD surgery) using a PMSG (200 or 400 iu)-GnRH pulse (250 ng i.v. for 96 h)-GnRH bolus (10 micrograms i.v.) regimen after pretreating the animals with GnRH pulses (250 ng i.v. for 14 days). On all occasions the ovulation rates were significantly higher (P < 0.05) in BB ewes (n = 6 or 7) than in ++ animals (n = 7). No differences between the genotypes were noted with respect to the mean concentrations of progesterone in plasma notwithstanding the differences in ovulation rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345486 TI - Calcium channel blockers: do they offer renal protection? AB - Calcium channel blockers are used in the treatment of hypertension because of their ability to decrease peripheral vascular resistance. Recent research has suggested that these drugs also preserve or improve renal function in patients with essential hypertensive renal disease, diabetic renal disease, and in renal transplant recipients with or without cyclosporine therapy. In general, studies in both animal models and humans have demonstrated maintenance or reduction in renal vascular resistance, and preservation or enhancement of renal blood flow and glomerular filtration rate. In addition, calcium channel blockers appear to have a positive effect on renal haemodynamic function in the setting of diabetes mellitus; prospective trials have demonstrated reductions in urinary protein excretion in these patients. Current evidence suggests that calcium channel blockers are well suited for the treatment of patients with hypertensive disease even in the presence of renal impairment. PMID- 8345487 TI - Developmental vascular biology and the early phases of essential hypertension in the young. PMID- 8345488 TI - Determinants of retinal vascular abnormalities in children and adolescents with essential hypertension. AB - The predictors of retinal vascular abnormalities in patients with elevated BP have not been studied extensively in children or adults. The purpose of this study was to investigate potential correlates of arteriolar narrowing, tortuosity and arteriovenous nicking in a population of children and adolescents with essential hypertension. A total of 97 subjects, aged 6-23 years, were studied. Retinal vascular abnormalities were determined by photographs of the optic fundus which were interpreted independently by two opthalmologists. In 50 subjects (51%) there were one or more abnormalities. Potential correlates of retinal abnormalities included: (1) demographic factors, (2) body size, (3) level of BP and duration of hypertension, (4) family history of cardiovascular disease, (5) treatment with antihypertensive medication, (6) dietary sodium intake, (7) laboratory analyses, (8) the reactivity of BP and heart rate to playing a video game, and (9) cardiovascular reactivity to exercise. Using stepwise multiple logistic regression, the variables that were independently associated with the presence of retinal vascular abnormalities were family income, dietary sodium intake, fasting blood glucose, pulse pressure during mental stress and the change in SBP from rest to maximum exercise. In addition, subjects with more than one retinal vascular abnormality had higher average DBP during follow-up in the Hypertension Clinic and a smaller rise in SBP from rest to maximum exercise. Identification of these independent predictors of retinal vascular abnormalities and factors associated with more than one abnormality may provide insight into the pathogenesis of hypertensive vascular disease. PMID- 8345489 TI - Lifestyle factors associated with geographic blood pressure variations among men and women in the UK. AB - The importance of various factors in explaining geographical BP variations in the UK has been examined among 2,596 men and women living in nine British towns. Associations between BP and potential explanatory variables have been examined first for individual subjects (within-population), and second for towns (between populations). The factors showing associations with BP that were consistent within-population and between-towns were BMI, urine sodium/potassium ratio (Na/K), alcohol and anxiety at examination for men, and BMI, Na/K and anxiety at examination for women. After adjustment for these factors and age, the male BP differences between the nine towns were reduced from 10.1 mmHg systolic in men (P = 0.001) to 7.1 mmHg (P = 0.04), and from 5.9 mmHg diastolic (P = < 0.0001) to 5.5 mmHg (P < 0.0001). For women, adjustment only marginally reduced the between town systolic differences from 5.6 mmHg (P = 0.05) to 5.5 mmHg (P = 0.3) and increased the diastolic differences from 3.7 mmHg diastolic (P = 0.03) to 5.0 mmHg (P < 0.0001). It is concluded that BMI, alcohol consumption and the Na/K ratio play an important part in the pattern of male SBP variations in the UK. The factors associated with female geographical differences in BP were less clear, but BMI and Na/K ratio appear to be important. This study has been unable to identify factors associated with geographical differences in DBP, with the possible exception of BMI in men. However, as systolic pressure is recognised to be more strongly associated with cardiovascular outcome than diastolic pressure, it can be recommended that primary prevention strategies aimed at reducing the population mean level of BP should involve efforts to reduce overweight, alcohol consumption and the Na/K ratio. PMID- 8345490 TI - Urine albumin excretion in healthy subjects. AB - The relationship between cardiovascular risk factors and urine albumin excretion were studied in 474 healthy office workers. Albumin concentration was measured fresh in first morning midstream urines. Lifestyle details, oscillometric BP and lipids were assessed. Subjects with urine albumin concentration above the median (5.30 mg/l) were compared with those with albumin concentration below the median. Subjects with above median urinary albumin concentration had higher systolic blood pressure (mean 115.2 vs. 113.1 mm Hg for above median, respectively, P = 0.06), were more likely to be male (56.8 vs. 45.0%, respectively, P = 0.01) and to have lower levels of high density lipoprotein (HDL)-cholesterol (mean 1.34 vs. 1.41 mmol/l, P = 0.006). Multivariate analysis following adjustment for urine creatinine concentration to allow for urine volume confirmed the relationship with systolic blood pressure (P = 0.01) and sex (P = 0.02), and in addition revealed a relationship with alcohol intake approaching significance (mean intake 70.8 and 76.0 g/week, respectively, P = 0.06). The univariate finding of increased albuminuria with lower HDL-cholesterol appeared to be attributable to the associated relationships with male sex and lower alcohol intake. The relationships between albumin excretion and BP, male sex and alcohol intake may reflect the effects of asymptomatic developing arterial disease. The relationship with BP may also be a consequence of effects on glomerular hydrostatic or interstitial renal pressure on albumin filtration or resorption. Very low level urine albumin excretion in healthy subjects is associated with factors which predict arterial disease. Urine albumin excretion may prove to be a useful early marker of cardiovascular disease in population studies. PMID- 8345491 TI - Plasma concentrations and comparisons of brain and atrial natriuretic peptide in normal subjects and in patients with essential hypertension. AB - We have developed a radioimmunoassay for the measurement of immunoreactive BNP (1 32) in human plasma. Simultaneous measurement of ANP have also been carried out to allow for direct comparison between circulating BNP and ANP. Plasma levels of immunoreactive BNP (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in 50 patients with essential hypertension (1.6 +/- 0.2 pmol/l, P < 0.02). Similarly, in patients with essential hypertension plasma levels of ANP were also significantly raised (5.5 +/- 0.6 pmol/l, P < 0.001) when compared with the group of normal healthy subjects (2.8 +/- 0.2 pmol/l). ANP was significantly higher than BNP in normal subjects and in patients with essential hypertension, with ANP/BNP ratios of 2.8 +/- 0.2 and 3.8 +/- 0.3, respectively, in these two groups. A major finding was a significant and positive association between plasma levels of both BNP and ANP within the healthy subjects (r = 0.49, P < 0.05, n = 36) and within the hypertensive subjects (r = 0.76, P < 0.001, n = 50). When all plasma values for BNP and ANP were taken together for both groups, there was an overall correlation coefficient of 0.65 (P < 0.001, n = 86). Both BNP and ANP had significant positive associations with age in hypertensive patients, with correlation coefficients of 0.53 (P < 0.001, n = 50) and of 0.53 (P < 0.001, n = 50) for BNP and ANP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345492 TI - Relationship between autonomic dysfunction and BP variability in subjects with diabetes mellitus. AB - Autonomic vagal heart rate (HR) control, office BP and ambulatory BP were examined in 54 diabetic subjects, aged 63 +/- 6 years. Sixteen subjects were insulin-dependent. The HR response to deep breathing (the bradypnoea test) was used to evaluate the vagal HR control, and ambulatory BP was determined by the Spacelabs 5200 system (one determination every 15 minutes, for 24 hours). Twenty seven subjects had normal office BP (SBP < or = 140 mmHg and DBP < or = 90 mmHg), seven had established hypertension (SBP > or = 160 mmHg and DBP > or = 95 mmHg) and 30 were borderline hypertensives. Over the total group, office systolic/diastolic BP (mean +/- SD) was 142 +/- 20/85 +/- 10 mmg. Systolic/diastolic ambulatory BP was 123 +/- 13/77 +/- 10 mmHg and ambulatory HR was 70 +/- 8 beats/min. Because of the small age range of our subjects, the HR score was not correlated with age (r = 0.19, NS). The HR score was not correlated with the levels of office and ambulatory pressures. In contrast, it was significantly correlated with the variability of ambulatory SBP, whether the variability was defined by the pressure standard deviation, or by the ratio SD/mean value (r = 0.40, P = 0.005 and r = 0.33, P < 0.017, respectively). We suggest that an impairment of the autonomic control in diabetics might induce an increase in variability of SBP. BP variability might play a role in the cardiovascular complications observed in diabetics. PMID- 8345493 TI - WHO-WHL Hypertension Management Audit Project. AB - The quality of the control of hypertension has been assessed in 18 European population groups, in a multicentre cooperative project. Five approaches were taken: epidemiological survey, clinical evaluation of samples of patient records, assessment of patient satisfaction, exploration of physicians' attitudes and knowledge, and drug utilisation studies. The participating centres could choose any or all of the above approaches; a total of 31 subprojects was carried out. Undiagnosed hypertension varied in different centres from 17% to 34% of all hypertension, and not more than 29% of all treated hypertensive patients had attained normal BP. Diuretics were the most commonly prescribed drugs, followed by beta-blockers. Although physicians expressed their concern about other cardiovascular risk factors and declared that they considered nonpharmacological treatment important, the findings in the patient survey did not confirm such attitudes. Finally, an analysis of patient satisfaction showed a mixed pattern. In conclusion, the control of hypertension in populations, through detection and treatment, as well as patient education and physician information, was studied. PMID- 8345494 TI - Nitrendipine in older patients with isolated systolic hypertension: second progress report on the SYST-EUR trial. AB - This report from the double-blind placebo-controlled SYST-EUR trial investigated whether modern antihypertensive drugs are suitable for maintaining long-term BP control in older (> or = 60 years of age) subjects with isolated systolic hypertension (SBP 160-219 mmHg and DBP < 95 mmHg). Active treatment consisted of nitredipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), if necessary to reduce SBP to < 150 mmHg and by > or = 20 mmHg. Matching placebos were used in the control group. This analysis was restricted to 18 months of follow-up. The placebo (n = 456) and active treatment (n = 485) groups had similar characteristics at randomisation (sitting pressure 176/85 mmHg; age 73 years). SBP fell (P < 0.001) on average 10 mmHg more on active treatment than on placebo and DBP 4 mmHg more. Fewer patients remained on monotherapy in the placebo than in the active treatment group (P < 0.001); on placebo the second and third line medications were started earlier (P < 0.001). Nitrendipine tablets were discontinued in nine patients on placebo and in 29 patients assigned to active treatment (P < 0.001). In conclusion, a significant BP reduction can be achieved and maintained in older patients with isolated systolic hypertension treated with a calcium antagonist (associated with a converting-enzyme inhibitor and a thiazide, where necessary). Whether this BP reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation. PMID- 8345495 TI - Blood pressure, plasma catecholamine and renin responses to caffeine in elderly hypertensives. AB - In young hypertensive patients, after a short period of abstention, caffeine ingestion has a significant pressor effect, although the acute cardiovascular responses have not been reported in elderly hypertensives. This study assessed the acute changes in BP, pulse rate, plasma renin activity (PRA) and arterialised plasma catecholamines after 250 mg of caffeine and matching placebo following 12 and 48 hours of caffeine abstention. After 48 hours caffeine abstention supine SBP was higher over the 120 minute study period following acute caffeine loading than following placebo (10 mmHg; 95% Cl 3-17 mmHg, P = 0.016) although the overall post-caffeine rise from baseline values was small (2 mmHg; -3 to 8 mmHg, P = 0.30). Similar differences were seen for supine DBP and standing SBP and DBP although pulse rate was unchanged throughout. After 12 hours abstention no acute pressor effect of caffeine was seen, in fact SBP fell over the study period (-5 mmHg; -10 to 0 mmHg, P = 0.05), and there was no difference between the caffeine and placebo phases. No change in plasma catecholamines or PRA values was found during any of the phases. These results suggest that in elderly hypertensives the pressor effect of caffeine (the equivalent of two to three cups of coffee) is small even after prolonged abstention. After the shorter abstention period, of the duration likely to be seen in clinical practice, no pressor response to caffeine was demonstrated. It is unlikely that acute caffeine ingestion has a significant effect on clinic BP measurements in elderly hypertensives who are regular caffeine consumers. PMID- 8345496 TI - Psychomotor performance in elderly hypertensive patients. AB - The psychomotor performance of 25 elderly patients with mild to moderate hypertension (aged 62-78 years, SBP = 162-212 mmHg; DBP = 98-124 mmHg) was compared with 25 age-matched controls (SBP = 110-160 mmHg; DBP = 64-92 mmHg). The hypertensive subjects did not have evidence of target-organ damage and were on no antihypertensive treatment at the time of assessment. Performance on a range of tests: symbol/digit substitution test (SDST) (34.3 vs. 39.5, P < 0.01), continuous attention test (CAT) (33 vs. 36.2, P < 0.01), choice reaction time (CRT) (270 ms vs. 320 ms, P < 0.01), paired word association test (PWAT) (4.1 vs. 7.0, P < 0.001) and inspection time threshold (INSP) (158 ms vs. 52 ms, P < 0.001), showed significant impairment in the hypertensive group compared with controls. These differences did not correlate with the duration of hypertension or degree of BP elevation. The impairment in hypertensive subjects was stable over a four week period. These results suggest the occurrence of a functional and possibly reversible impairment of psychomotor performance in elderly hypertensive patients which may have implications for antihypertensive treatment. PMID- 8345497 TI - Effect of antihypertensive treatment on psychomotor performance in the elderly. AB - The psychomotor effects of control of hypertension were studied in a parallel group comparison of 25 elderly hypertensives (aged 61-79 years; SBP = 192 (range 162-212) mmHg; DBP = 112 (range 98-124) mmHg) shown to have psychomotor impairment when not on antihypertensive treatment. Single blind treatment was commenced with placebo or a diuretic: atenolol, nifedipine or captopril (5 x n = 5). A range of tests using an automated psychomotor test battery showed a significant improvement compared with placebo in tests of attention and psychomotor speed in subjects rendered normotensive (n = 18) after treatment for one week (SDST + 3.8, P < 0.001; CAT + 1.2, P < 0.03; PWAT + 1.9, P < 0.004; INSP -49.5 ms, P < 0.001). Subgroup analysis suggested greater improvement in psychomotor performance with captopril, but this was equivocal because of the small sample size in each group. Hence, the psychomotor effects of treatment with nifedipine and captopril were compared in a further 13 hypertensives (aged 62-76 years; SBP = 178 (range 169-193) mmHg; DBP = 106 (range 97-117) mmHg) in a double blind crossover study. With both drugs, control of hypertension was associated with a significant and comparable improvement in several psychomotor performance measures. The results suggest that impaired psychomotor performance due to hypertension improves with antihypertensive treatment. The improvement appears to be related to control of hypertension rather than to the direct CNS effects of antihypertensive drugs. PMID- 8345498 TI - Nocturnal hypotension and ACE inhibitors. AB - Thirty essential hypertensive subjects had their BP measured by 24h ambulatory monitoring before (first placebo period) and after exposure to antihypertensive therapy with either enalapril (four weeks) or nitrendipine (six weeks). Similar measures of BP were obtained during a second placebo period intercalated between the two active drugs. The 24h averages of systolic and diastolic pressures were higher during placebo (148 +/- 3/91 +/- 1 mmHg, respectively) than during treatment periods. Four weeks of treatment with enalapril reduced arterial pressure to a 24h average of 137 +/- 1/86 +/- 1 mmHg while nitrendipine given for six weeks lowered BP to an average of 135 +/- 1/84 +/- 1 mmHg. The antihypertensive effect of the drugs was of a comparable magnitude (P > 0.05). In addition both drugs produced analogous reductions in BP during the day (07.00 to 23.00 h). In contrast, the nocturnal fall in BP was significantly greater during treatment with nitrendipine. Average systolic and diastolic pressures between 23.00 h and 07.00 h were 133 +/- 1 mmHg and 82 +/- 2 mmHg with enalapril compared with 129 +/- 3 mmHg (P < 0.01) and 77 +/- 3 mmHg (P < 0.01) with nitrendipine, respectively. These data suggest that antihypertensive agents show important differences in terms of their action on the mechanisms that regulate BP during sleep. Medications that amplify the otherwise physiological fall in BP during sleep may add risk to patients with impaired coronary vasodilator reserve owing to ventricular hypertrophy, coronary atherosclerosis, or both. PMID- 8345499 TI - Combination therapy with verapamil and nitrendipine in patients with hypertension. AB - Forty patients with mild to moderate hypertension were divided into two groups, 20 patients (group A) received 240 mg verapamil and 20 patients (group B) received 20 mg nitrendipine daily during the first six weeks. During the second six weeks, all 40 patients were given 10 mg nitrendipine plus 120 mg verapamil. After the combination therapy, group B received verapamil, 240 mg and group A nitrendipine 20 mg for a further period of six weeks. When verapamil and nitrendipine were used alone, BP decreased significantly in each group. However, BP decreased more when the combination therapy was used and increased when the treatment was changed to single drug therapy from the two-drug combination. In addition, side-effects were three to four times fewer during the combination therapy. It is concluded that the combination of two different calcium antagonists in the treatment of hypertension provides a new dimension to therapy. PMID- 8345501 TI - Attenuation of nocturnal BP fall in essential hypertensives with cerebral infarction. PMID- 8345500 TI - Cuff sizes. PMID- 8345502 TI - Multiple phaeochromocytoma with renal artery stenosis or occlusion: report of two cases. PMID- 8345503 TI - Serum lipids, lipoproteins and apolipoproteins in untreated essential hypertension. PMID- 8345504 TI - Influence of subinhibitory levels of antibiotics on expression of Escherichia coli lipopolysaccharide and binding of anti-lipopolysaccharide monoclonal antibodies. AB - The expression of Escherichia coli lipopolysaccharide (LPS) and the binding capacity of anti-LPS monoclonal antibodies (MAbs) to E. coli grown in the presence or absence of subinhibitory concentrations of various antibiotics was studied. Four E. coli strains (three clinical blood-culture isolates and an isogenic, non-capsulate mutant of the O18:K1 parent) were grown in the presence of the beta-lactam antibiotic, ampicillin, the aminoglycoside gentamicin, the fluoroquinolone ciprofloxacin and chloramphenicol. The techniques of silver staining, immunoblotting, whole-cell ELISA and flow cytometry were all used to monitor the expression of LPS on the bacteria and the binding of the anti-LPS MAbs. Treatment with ampicillin, chloramphenicol and ciprofloxacin resulted in enhanced binding of anti-core reactive MAbs to most E. coli strains. Overall, treatment with gentamicin produced the least effect on MAb binding. The presence of chloramphenicol decreased the expression of high molecular mass O-antigen or increased the expression of low molecular mass substituted E. coli LPS or both. These results further illustrate that LPS core, especially the inner-core region, becomes more accessible to antibodies when bacteria are grown in the presence of certain antibiotics. Possible synergy between antibodies and antibiotics for treatment of septicaemia and septic shock remains an intriguing possibility. PMID- 8345505 TI - Characterisation of strains of Aeromonas spp. by phenotype and whole-cell protein fingerprint. AB - Sixty-eight isolates of Aeromonas spp. were examined biochemically and their cell proteins were analysed by silver-stained SDS-PAGE. Protein fingerprints did not correlate with phenotype. However, consideration of both phenotype and fingerprint showed clustering of epidemiologically related isolates. There was also evidence that similar strains could be found in infected people and water or other environmental samples. PMID- 8345506 TI - Enterotoxigenic bacteria in the sudden infant death syndrome. AB - Faecal samples from 123 infants who died with sudden infant death syndrome (SIDS) and from a comparative group of 52 age-matched babies were analysed for toxigenic bacteria and their toxins. Serum samples from the SIDS infants were also analysed for these toxins. A significantly higher proportion of toxigenic bacteria and their toxins were found in faecal samples of SIDS babies than in samples from the comparative group. These toxins were also found in serum from the SIDS babies. Clostridium perfringens was found in 54 (45.4%) of 119 SIDS cases compared with 10 (19.6%) of 51 healthy babies (chi 2 = 10.1, p < 0.01); C. difficile in 33 (27.7%) of 119 SIDS cases compared with 8 (14.8%) of 54 healthy babies (chi 2 = 3.43ns, p < 0.1); Staphylococcus aureus in 12 (27.3%; 66.7% enterotoxigenic) of 44 SIDS cases compared with 12 (85.7%; non-enterotoxigenic) of 14 healthy babies (chi 2 = 14.9, p < 0.001); C. botulinum in 6 (5.0%) of 120 SIDS cases compared with 0 of 53 healthy babies (chi 2 = 2.74, p < 0.1). Campylobacter jejuni, Yersinia enterocolitica, Vibrio parahaemolyticus, salmonellae and Bacillus cereus were not detected. Heat-labile toxin, lethal to mice (HLML) was found in 32 (27.1%) of 118 SIDS faecal samples compared with 5 (10.6%) of 47 healthy babies (chi 2 = 5.24, p < 0.05); cytotoxins in 38 (30.9%) of 123 SIDS faecal samples compared with 0 of 21 of healthy babies (chi 2 = 8.8, p < 0.01) and 24 (27.6%) of 87 SIDS serum samples. C. perfringens enterotoxin was detected in 33 (34.4%) of 96 SIDS faecal extracts compared with 0 of 23 of healthy babies (chi 2 = 10.94, p < 0.001), and in 27 (24.5%) of 110 SIDS serum samples. C. perfringens alpha-toxin (presumptive) was detected in 14 (17.5%) of 80 SIDS faecal extracts compared with 0 of 17 from healthy babies (chi 2 = 3.5ns, p congruent to 0.05) and in 2 (2.3%) of 87 SIDS serum samples. C. difficile toxin was detected in four SIDS faecal samples and two serum samples. C. botulinum toxin was detected in only one of 120 SIDS faecal samples compared with none of 49 from healthy babies. Staphylococcal enterotoxins were detected in 8 (19.5%) of 41 SIDS faecal samples compared with 0 of 19 from healthy babies (chi 2 = 4.278, p < 0.05), and in 4 (10.8%) of 37 SIDS serum samples.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345507 TI - Detection of Staphylococcus aureus with biotinylated monoclonal antibodies directed against staphylococcal TNase complexed to avidin-peroxidase in a rapid sandwich enzyme-linked immunofiltration assay (sELIFA). AB - For rapid identification of Staphylococcus aureus, a monoclonal antibody (MAb) biotin-avidin-peroxidase complex, directed against the S. aureus thermostable nuclease (TNase), was formed and used in a rapid three-step sandwich enzyme linked immunofiltration assay (sELIFA) and a three-step sandwich enzyme-linked immunosorbent assay (sELISA). The MAb-peroxidase complex was formed by incubating the biotinylated MAbs with a streptavidin-peroxidase conjugate and the complex was purified by gel permeation chromatography. When compared with a four-step MAb based sELISA described previously, this complex permitted one reagent step to be omitted in a three-step sELISA, and the test time was significantly reduced. The test sensitivity was slightly reduced in the three-step ELISA (detection limit 1.0-2.0 ng of TNase/ml) when compared to the four-step sELISA (detection limit 0.5-1.0 ng of TNase/ml). The sELIFA method was based on the filtration of bacterial culture supernates through nitrocellulose membrane disks pre-spotted with a MAb directed against the S. aureus TNase, followed by detection with the MAb-peroxidase complex (three-step sELIFA). A detection limit of 0.5-2.0 ng of TNase/ml was achieved with the three-step sELIFA, depending on the filtrate volume of culture supernates. The total test time was 10-15 min when pre-spotted and blocked membranes were used. A total of 85 bacterial strains was tested in the sELIFA. All the 28 S. aureus strains showed positive results, but none of the 57 non-S. aureus strains did so, although some of these produced thermostable nuclease activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345508 TI - Human immune response to the 18-kDa outer-membrane antigen of Vibrio cholerae. AB - The serum IgG response of human volunteers challenged with Vibrio cholerae O1 was analysed for reactivity to V. cholerae O1 outer-membrane antigens by enzyme linked immunosorbent assay (ELISA) and the immunoblot technique. Purified outer membrane antigen preparations from vibrios grown in low-iron conditions were separated by SDS-PAGE. Specific immunoblot reactions of human sera showed that an 18-kDa antigen, cholera protective antigen, was the major antigen with which sera reacted. ELISA revealed an increase in antibody to the 18-kDa antigen in nine of 10 challenged volunteers. This response was independent of the biotype and serotype of the V. cholerae O1 challenge strain. Cholera protective antigen appears to be one of the major outer-membrane antigens involved in the human immune response to infection with V. cholerae. PMID- 8345509 TI - Mortality rates amongst mice with endogenous septicaemia caused by Pseudomonas aeruginosa isolates from various clinical sources. AB - Mice that had been treated with cyclophosphamide and ampicillin were fed with Pseudomonas aeruginosa. These procedures induced an endogenous septicaemia under conditions mimicking the pathophysiology of the disease in man. This model was used to compare the mortality rates in mice infected with P. aeruginosa isolates from various clinical sources. Mortality rates in mice given isolates from blood cultures had a broad range (0-100%), but the mean rate was significantly higher than with isolates from other infection sites. Moreover, blood isolates persisted in the intestines of mice after oral inoculation, whereas most isolates from other sources were gradually eliminated. Most P. aeruginosa isolates from blood culture produced significantly higher levels of exotoxin A and total proteases than isolates from other infection sites. Amongst the blood isolates, all but one of the lethal strains produced large quantities of exotoxin A or total proteases or both. Taken together, the results suggest that the ability of P. aeruginosa to adhere to the intestinal tract and to produce high levels of exo-enzymes may contribute to the development of fatal septicaemia. PMID- 8345510 TI - The application of flow cytometry to the study of bacterial responses to antibiotics. AB - Experiments were performed to determine whether a modern flow cytometer could be used to study bacterial populations in suspension, with particular reference to their morphological characteristics and their responses to antibiotics. The FACScan, a commercial benchtop flow cytometer fitted with an air-cooled laser, designed primarily for the study of eukaryotic peripheral blood mononuclear cells, yielded reproducible data relating to bacterial shape and internal architecture. It was sensitive enough to detect changes in bacterial morphology on entry into the growth cycle and after exposure to antibiotics. Antibiotic induced morphological changes affecting subpopulations of bacteria were sufficiently specific to allow differentiation between antibiotics with different cell-wall enzyme targets. Simultaneously, the effect of such antibiotics on the integrity of the outer cell membrane of Escherichia coli was assessed by measurement of the association of the nucleic acid-binding dye propidium iodide with the bacteria. These experiments demonstrated complex patterns of probable cell-wall leakage, related to the modes of action of the antibiotics. The FACScan is a useful and sensitive tool for the study of the morphology and physiology of bacterial populations in suspension, and is especially applicable to the study of antibiotic action. PMID- 8345511 TI - Use of tellurite for the selection of verocytotoxigenic Escherichia coli O157. AB - Potassium tellurite was assessed for the selection of verocytotoxigenic (VT+) Escherichia coli O157. MICs were higher for VT+ E. coli O157 than for other strains of E. coli and for Aeromonas spp. MacConkey medium containing sorbitol, tellurite and cefixime (TC-SMAC) permitted the growth of VT+ E. coli O157 and Shigella sonnei but partially or completely inhibited the growth of 67% of other strains of E. coli and all or most strains of other sorbitol-non-fermenting species tested. Of 391 rectal swabs from cattle screened on TC-SMAC medium, 26 yielded isolates of VT+ E. coli O157 whereas sorbitol-MacConkey medium with cefixime and rhamnose yielded only nine isolates. Inclusion of potassium tellurite in sorbitol-MacConkey agar markedly increased the rate of isolation of VT+ E. coli O157 from cattle rectal swabs and may do so for other types of specimen. PMID- 8345512 TI - A microbiologist's perspective. PMID- 8345513 TI - Metallo-beta-lactamases--a new therapeutic challenge. PMID- 8345514 TI - kappa B-like motifs regulate the induction of immune genes in Drosophila. AB - The mammalian transcription factor NF-kappa B regulates a number of genes involved in immune and acute phase responses, by interacting with a nucleotide sequence element, the kappa B-motif. In this work we demonstrate the participation of similar motifs in the immune response of insects as well: kappa B-like motifs have a regulatory role in the synthesis of cecropins, a set of anti bacterial peptides, triggered by the presence of bacterial cell wall components in the insect blood. We show that the upstream region of the Cecropin gene CecA1 contains elements responsible for inducible and tissue-specific expression. Furthermore, a trimer of kappa B-like motif confers high levels of inducible expression from the reporter gene, after transfection in a Drosophila blood cell line. As in the moth Hyalophora cecropia, stimulation with bacterial lipopolysaccharide induces a nuclear factor that specifically binds to the kappa B-like motif. Our data suggest a functional and evolutionary relationship between these insect immune response factors and the mammalian NF-kappa B. PMID- 8345515 TI - A conformational change in the actin subunit can change the flexibility of the actin filament. AB - The mechanical properties of F-actin are very significant, given the central structural role played by actin filaments within muscle and the cytoskeleton. We have determined that actin can exist in a state that has a fourfold increase in flexibility over normal F-actin, and nucleotide. Three-dimensional reconstructions from electron micrographs suggest that this increased flexibility arises from a rotation of subdomain-2, the smallest subdomain, of the actin subunit. The modulation of actin's flexibility by Ca2+ and Mg2+ may have important physiological consequences within the cell. Further, since it has been shown that myosin-decorated actin filaments are more flexible than pure F-actin, it is possible that myosin induces this more flexible state in actin. PMID- 8345516 TI - Nucleotide sequence requirements for self-cleavage of Neurospora VS RNA. AB - We have used several complementary approaches to investigate the minimal contiguous sequence required for the in vitro self cleavage reaction performed by Neurospora VS RNA. Deletion analysis and site-directed mutagenesis revealed that only a single nucleotide is required upstream of the self-cleavage site, and that the identity of this nucleotide is not critical. This distinguishes VS RNA from all currently known ribozymes except hepatitis delta virus RNA. The shortest contiguous sequence capable of cleavage contains 153 nt downstream of the cleavage site. Linker insertion mutagenesis suggests that much of this downstream sequence is important for self-cleavage. Comparative sequence analysis of the VS plasmid from six natural isolates supports the importance in vivo of the minimal region determined by in vitro methods. Also, phylogenetic analysis raises the possibility of a recent horizontal transfer of the VS plasmid from Neurospora intermedia to Neurospora sitophila. PMID- 8345517 TI - Dynamics of in vitro assembly of 16 S rRNA into 30 S ribosomal subunits. AB - One of the important unsolved problems in the ribosome field is the molecular basis for the sequential and co-operative nature of ribosome assembly. As an approach to this problem, we have taken advantage of the temperature dependence of in vitro reconstitution and have used chemical probing methods to examine the conformation and reactivity of 16 S rRNA at successive stages during subunit assembly. One class of nucleotides displays reactivities similar to those observed in native 30 S particles when the RNA and protein are incubated in the absence of any heat step (0 degrees C effects). At 30 degrees C, where the assembly process takes 2 hours, other bases can be assigned to one of several additional kinetic classes, determined by the rate at which their chemical reactivities transit from levels observed in naked RNA to levels observed in fully assembled subunits: (1) fast (t1/2 = < 5 min at 30 degrees C); (2) slow (t1/2 = 15 to 30 min at 30 degrees C); (3) delayed slow (t1/2 = 30 to 60 min at 30 degrees C). Finally, several nucleotides display transient kinetics in their reactivities, showing increasing reactivity at early time points and becoming protected later in assembly; most of these effects correspond to residues that were previously shown to display reciprocal enhancement and protection patterns during step-wise in vitro assembly. These findings, together with our previous studies using purified individual proteins lead to the following conclusions: (1) there is a predominant 5' to 3' polarity to in vitro assembly, even though it is uncoupled from transcription; (2) portions of the central and 3' major domains fold into an active conformation only at a very late stage of assembly; (3) bases footprinted by late-assembling proteins, according to the 30 S subunit assembly map, show generally slower kinetics than residues footprinted by proteins that bind early in the assembly map, providing direct evidence for the sequential nature of the in vitro assembly process; (4) most proteins are associated with nucleotides that fall into more than one kinetic class, suggesting that assembly proceeds through multiple pathways, or that individual proteins interact sequentially with different regions of the RNA. PMID- 8345518 TI - Nutrient-responsive promoter elements of the V4 gene of Dictyostelium discoideum. AB - Expression of the V4 gene of Dictyostelium discoideum is required for the transition from growth to development in response to an altered nutrient environment. In addition, the expression itself is sensitive to the types and amounts of nutrients supporting growth. We describe the structure of the two copies of the V4 gene and the relationship between these genes and the two V4 mRNA species produced during growth. In addition, three regions were identified within the upstream sequences of the V4b gene that are important for proper transcription. At least two of the regions can, independently of the others, confer deactivation of transcription upon initiation of development and thus serve as redundant regulatory sequences. However, the regions are differentially responsive to the types and amounts of nutrients present in the cell's environment and thus are distinct from one another. PMID- 8345519 TI - The minus 35-recognition region of Escherichia coli sigma 70 is inessential for initiation of transcription at an "extended minus 10" promoter. AB - It is known that Escherichia coli promoters having the major minus 10 consensus sequence TATAAT, but lacking significant resemblance to consensus in the minus 35 region, allow transcriptional initiation in vivo and in vitro if they have an additional TGn motif immediately upstream of minus 10. To determine whether region 4.2 of sigma 70, whose normal role is sequence recognition at minus 35, is unnecessary for initiation of transcription at such "extended minus 10" promoters, we modified the sigma 70 gene so as to generate a carboxy-truncated polypeptide lacking the last 84 amino acids and therefore missing region 4.2. Our results show that both the intact and truncated sigma 70 allow purified RNA polymerase to initiate efficiently and specifically at an extended minus 10 promoter, whereas only the intact sigma 70 permits efficient initiation at normal promoters (defined by minus 35 and minus 10 hexamer sequences). PMID- 8345520 TI - Cloning, DNA sequence, functional analysis and transcriptional regulation of the genes encoding dipicolinic acid synthetase required for sporulation in Bacillus subtilis. AB - Dipicolinic acid (DPA) is a small polar molecule that accumulates to high concentrations in bacterial endospores, and is thought to play a role in spore heat resistance, or the maintenance of heat resistance. Previous work has shown that mutations in the spoVF locus of Bacillus subtilis prevent the formation of DPA, and give rise to heat-sensitive spores. Addition of exogenous DPA during spore development led to the restoration of heat resistance. This suggested that the spoVF locus encoded dipicolinic acid synthetase, the enzyme thought to catalyse the single reaction needed to synthesise DPA from dihydroxydipicolinic acid, an intermediate in the lysine biosynthetic pathway. We have now cloned and sequenced the spoVF locus of Bacillus subtilis and show that it comprises two coordinately regulated genes, now designated dpaA and dpaB. Expression of fragments of the dpa operon in Escherichia coli has shown that the two gene products together specify DPA synthetase activity. The promoter of the dpa operon, which lies just upstream of the first gene, has been identified by primer extension analysis. Sequences in this region show strong sequence similarity to several promoters recognized by the sigma K form of RNA polymerase. Transcription from this promoter was detected four hours after the onset of sporulation, at about the same time that sigma K activity is known to appear. Furthermore, transcription was abolished by mutations in a series of genes that are known to be required for the synthesis of active sigma K. These results are in accordance with previous work indicating that DPA synthetase activity was present only during the late stages of sporulation and specifically in the mother cell compartment. Transcription was enhanced by a gerE mutation, indicating that, like the previously described cotA gene, spoVF is negatively regulated by GerE. The mother-cell-specific synthesis of an enzyme responsible for a compound that accumulates to high concentrations in the prespore raises interesting questions about intercellular transport mechanisms. PMID- 8345521 TI - Different mechanisms of recognition of bacteriophage Q beta plus and minus strand RNAs by Q beta replicase. AB - Our earlier work on the recognition of Q beta plus strand RNA by replicase had shown by RNase degradation and by electron microscopic techniques that specific binding interactions occurred at two internal sites, the S-site and the M-site, but not at the 3'-end, i.e. the site of initiation of synthesis. Using essentially similar methods, we have found now for binding complexes of replicase with the minus strand a completely different pattern, namely considerable terminal binding, whereas binding to internal sites was without detectable specificity. In the case of plus strand complexes, simultaneous binding at the two internal sites and at a terminal site could be demonstrated by electron microscopy after initiation of RNA synthesis in the presence of host factor, GTP and ATP. A variant plus strand RNA containing a 490 nucleotide duplication near the 5'-end resulted in similar double-looped complexes, however with an elongated free arm, showing that the protein-bound terminal site was the 3'-end of the RNA. Interestingly, the same two-looped structures were also found for complexes consisting of plus strand RNA and host factor without replicase. This suggests that the role of the host factor on the plus strand template is to bring the 3' end into the proximity of the S-site/M-site domain, where replicase can initiate on it. In contrast, the 3'-end of the minus strand appears to be directly available to the enzyme. PMID- 8345522 TI - Influence of fluctuations on DNA curvature. A comparison of flexible and static wedge models of intrinsically bent DNA. AB - Matrix-generator and Monte Carlo methods have been employed to study the influence of thermal fluctuations on the overall sizes and shapes of curved pieces of DNA. The DNA model involves the independent angular parameters relating successive base-pair steps: the sequence-dependent equilibrium values and fluctuations of the twist, tilt, and roll angles. The curved sequence under study is the (A5X5)n repeating polymer, the AA and XX steps having different equilibrium roll and twist values. Both planar circles and superhelices are analysed. Detailed comparison is made between the rigorous statistical mechanical representation of the DNA and simplified static models currently used in the literature. That is, a more realistic "flexible wedge" model is contrasted with the existing "static wedge" model of DNA curvature, which is demonstrated to be inadequate. The size of the coils is described by the unperturbed root-mean square end-to-end distance and the shape by a ratio of the principal moments of the radius of gyration. The moment ratios indicate that when DNA is relatively short (e.g. its length is shorter than half a turn of the static superhelix), the flexible chains are more "short and thick" than the static structure. The end-to end distances, however, are practically the same in the two models. For longer DNA fragments, the flexible chain is more extended in terms of the end-to-end distance and more globular in terms of the moment ratio. Thus, fluctuations "blur" the curvature of longer DNA fragments compared with static models. Furthermore, the overall average shape of slightly curved DNA subject to natural bending and twisting fluctuations is essentially indistinguishable from that of the corresponding "straight" DNA. Such configurational similarities are apparently responsible for the relative insensitivity of the polyacrylamide gel matrix to small degrees of DNA curvature. These findings raise serious questions regarding the quantitative estimation of wedge angles in DNA from electrophoretic experiments, based on static models. Comparison between planar circles and superhelices shows that when fluctuations are considered, the flexible circles are more spherical than the superhelices. The results imply that when DNA bending is exactly "in phase" with the helical repeat (i.e. when the DNA loop is exactly planar at 0 K), the DNA coil is packed more tightly than when bending and twisting are "out of phase" (and a superhelix is formed at 0 K). This finding is consistent with polyacrylamide gel electrophoresis data testifying to an increase in DNA retardation when twisting is more precisely "tuned".(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8345523 TI - Refined structures of the ligand-binding domain of the aspartate receptor from Salmonella typhimurium. AB - The aspartate receptor is a transmembrane-signalling protein that mediates chemotaxis behaviour in bacteria. Aspartate receptors in Salmonella typhimurium and Escherichia coli exist as dimers of two subunits in the presence as well as in the absence of aspartate. We have previously reported the three-dimensional structures of the external ligand-binding domain of the S. typhimurium aspartate receptor with and without bound aspartate. The external or periplasmic region of the aspartate receptor is a dimer of four-alpha-helical bundle subunits; a single aspartate molecule binds to one of two sites residing at the subunit interface, increasing the affinity of the subunits for one another. Here we report the results of a detailed analysis of the aspartate receptor ligand-binding domain structure (residues 25 to 188). The dimer interface between the twofold related subunits consists primarily of contacts mediated by the side-chains of the N terminal helix of each four-alpha-helical bundle subunit. The N-terminal helices pack approximately 20 degrees from parallel as an approximate coiled-coil super secondary structure. We have refined aspartate receptor ligand-binding domain structures in the presence and in the absence of a bound aromatic compound, 1,10 phenanthroline, to 2.2 A and 2.3 A resolution, respectively, as well as crystal structures in the presence of specifically bound Au(I), Hg(II) and Pt(IV) complex ions at 2.4 A, 3.0 A and 3.3 A resolution, respectively. The possible biological relevance of the aromatic ligand-binding site and the metal ion-binding sites is discussed. The dimer of four-alpha-helical bundle subunits composing the periplasmic region of the S. typhimurium aspartate receptor provides a basis for understanding the results of mutational analyses performed on related chemotaxis transmembrane receptors. The crystal structure analysis provides an explanation for the way in which mutations in the E. coli aspartate receptor affect its binding to the periplasmic maltose-binding protein and how mutations in the more distantly related E. coli Trg chemotaxis receptor affect its binding to the periplasmic ribose and glucose-galactose binding proteins. PMID- 8345524 TI - Long-range surface charge-charge interactions in proteins. Comparison of experimental results with calculations from a theoretical method. AB - Long-range coulombic interaction energies between surface-charges in barnase and subtilisin have been determined to provide data for calibrating theoretical methods. The pKa of His18 in barnase can be measured accurately by titrating the fluorescence of Trp94 that is significantly quenched on protonation of His18. The pKa of His64, the active site base of subtilisin, has previously been shown to be measured accurately from the pH dependence of kcat/Km for the hydrolysis of substrates. The titration curves of both histidine residues fit the theoretical equations for the ionization of single groups with great precision; the Hill constants for wild-type and mutant enzymes are all close to 1.0. The coulombic interaction energies of distant charged side-chains with the protonated form of His18 and His64 have been measured from changes in pKa of these residues on mutation of those charged side-chains. The interaction energies between single charges on the surfaces of the proteins at low ionic strength are small, some 0.3 0.5 kcal mol-1 at a distance of 12 A, and fall gradually with distance to 0.05 0.3 kcal mol-1 at 20 A. Multiple mutations are frequently additive. Effects are larger in subtilisin than in barnase, possibly related to the degree of solvent exposure of the charge. These data have been used to benchmark the finite difference method of calculating electrostatic interactions as implemented in the program DelPhi. There is reasonable agreement between the calculated and measured results as a function of both position and ionic strength. PMID- 8345525 TI - Prediction of protein secondary structure at better than 70% accuracy. AB - We have trained a two-layered feed-forward neural network on a non-redundant data base of 130 protein chains to predict the secondary structure of water-soluble proteins. A new key aspect is the use of evolutionary information in the form of multiple sequence alignments that are used as input in place of single sequences. The inclusion of protein family information in this form increases the prediction accuracy by six to eight percentage points. A combination of three levels of networks results in an overall three-state accuracy of 70.8% for globular proteins (sustained performance). If four membrane protein chains are included in the evaluation, the overall accuracy drops to 70.2%. The prediction is well balanced between alpha-helix, beta-strand and loop: 65% of the observed strand residues are predicted correctly. The accuracy in predicting the content of three secondary structure types is comparable to that of circular dichroism spectroscopy. The performance accuracy is verified by a sevenfold cross validation test, and an additional test on 26 recently solved proteins. Of particular practical importance is the definition of a position-specific reliability index. For half of the residues predicted with a high level of reliability the overall accuracy increases to better than 82%. A further strength of the method is the more realistic prediction of segment length. The protein family prediction method is available for testing by academic researchers via an electronic mail server. PMID- 8345526 TI - Crystallographic refinement and structure analysis of the complex of wheat germ agglutinin with a bivalent sialoglycopeptide from glycophorin A. AB - Wheat germ agglutinin (WGA) elicits a number of biological effects in erythrocytes as a result of specific binding to the transmembrane protein glycophorin A. The structure of co-crystals of WGA (isolectin 1: WGA1) with a bivalent sialoglycopeptide fragment of glycophorin A (T5), determined at 2.0 A resolution, has been further refined and analyzed with respect to ligand-induced changes in the tertiary structure, mobility, solvation, saccharide conformation and protein/saccharide interactions at three independent N-acetyl-D-neuraminic (NeuNAc) binding sites. The final model, which includes the two independent WGA1 monomers (composed of domains A, B, C and D), two positions for bound T5 sialo tetrasaccharide (NeuNAc-alpha 2,3-Gal-beta 1,3-(alpha 2,6-NeuNAc)GalNAc) and 386 water molecules, refined to a crystallographic R-factor of 17.1% (Fo > 1.0 sigma) and an average temperature factor of 31.99 A2. Comparisons between the tertiary structures of the liganded and unliganded WGA1 dimers indicate that the largest deviations from 2-fold symmetry are localized in domains engaged in sugar binding (B1 and C2) and at the C-terminal domain of monomer II (D2), forming a strong lattice contact. Interactions of the tetrasaccharide with amino acid ligands in the three binding sites and with water were carefully analyzed and compared. Bound conformations of terminal NeuNAc match to within a root-mean-square delta r of 0.3 A. The specificity-determining N-acetyl group superimposes best in comparison with other substituents of the sugar ring. Of the five domain binding sites that are not occupied in this dimeric crosslinked complex, only one is accessible to the NeuNAc monosaccharide as determined from a difference Fourier map at 3.0 A resolution. PMID- 8345527 TI - Localization of proteins HL29 and HL31 from Haloarcula marismortui within the 50 S ribosomal subunit by chemical crosslinking. AB - Isolated 50 S ribosomal subunits from the halophilic archaebacterium Haloarcula marismortui were treated in situ with the homobifunctional and cleavable crosslinking reagent dithiobis(succinimidyl propionate) (12 A). Several crosslinked complexes were obtained. Among these were the protein pairs HmaL4 HL29 and HmaL18-HL31; HL29 and HL31 are ribosomal proteins without any equivalent in eubacterial ribosomes. The crosslinked protein pairs were isolated on a preparative scale by combining conventional ion-exchange chromatography and reverse phase high-pressure liquid chromatography. The monomeric proteins involved in crosslink formation were unambiguously identified by two-dimensional gel electrophoresis and N-terminal or internal protein sequencing. Due to the homology between HmaL4 and HmaL18 and their Escherichia coli counterparts, and the roughly known location of these proteins within the 50 S subunit, our results demonstrate that HL29 is probably located in the centre of the large subunit in the vicinity of the peptidyltransferase domain, whereas HL31 must be situated within the central protuberance close to the region of the 5 S RNA. PMID- 8345528 TI - Crystallization and preliminary crystallographic characterization of aspartic proteinase-A from baker's yeast and its complexes with inhibitors. AB - The aspartic proteinase from yeast vacuoles, proteinase-A, has been crystallized with and without non-hydrolysable transition-state analogue inhibitors. The native enzyme crystals belong to the space group I2(1)2(1)2(1), with two molecules per asymmetric unit. The inhibitor complex crystals are trigonal with space group P3(2)21 and with one molecule in the asymmetric unit. Preliminary X ray analysis of both native enzyme and its complexes indicate that the complexes diffract to higher resolution than the native crystals. This is probably due to reduced flexibility in the enzyme-inhibitor complex. PMID- 8345529 TI - Purification and crystallization of Shiga toxin from Shigella dysenteriae. AB - The protein toxin produced by Shigella dysenteriae consists of one enzymatically active A subunit of 293 amino acid residues and five B subunits of 69 amino acid residues that are involved with cell attachment. The holotoxin has been purified by blue Sepharose and chromatofocusing column chromatography. Two crystal forms of purified holotoxin have been grown by vapor diffusion. One grows as fine needles, hexagonal in cross-section, which do not diffract well enough to characterize crystallographically. The second grows as thin plates that diffract to at least 3 A resolution. Their space group is P2(1)2(1)2(1) with unit cell dimensions of a = 132.0 A, b = 146.0 A and c = 82.5 A. The asymmetric unit of the crystals is likely to contain two AB5 units. PMID- 8345530 TI - Comparison of toxicities of acrylamide and 2,5-hexanedione in hens and rats on 3 week dosing regimens. AB - Survival rates, changes in body weight, gait/ataxia scores, and neuropathological lesions were compared between adult Long-Evans rats and adult White Leghorn hens given equivalent dosages of the peripheral neurotoxicants acrylamide and 2,5 hexanedione (12, 25, and 50 mg/kg acrylamide 3 times per week; or 75, 105, 150, 225, or 350 mg 2,5-hexanedione/kg/d, with hens receiving the lowest 3 dosages of 2,5-hexanedione and rats receiving the highest 3 dosages of this test compound). All rats survived the 3-wk acrylamide study period, although those given 50 mg/kg did not gain weight and showed alterations in gait. Hens given 50 mg/kg acrylamide were moribund by 2 wk and were sacrificed before the end of the 3-wk study period. By this time they had lost 29 +/- 3% of their body weight, but none showed significant renal or hepatic lesions on necropsy. Hens given all doses of acrylamide showed dose-related ataxia, weakness, and depression. Gait changes were seen in rats given the high dose of acrylamide for the 3-wk test period. Neuropathological studies revealed that both rats and hens given acrylamide had distal myelinated fibers with dose-related neurofilament-rich axonal swelling and Wallerian-like degeneration, better developed in the rodents. In addition, high dose acrylamide rats had recent necrosis of cerebellar Purkinje cells. Deaths occurred in all groups of hens given 2,5-hexanedione (75, 105, or 150 mg/kg) before sacrifice at 3 wk, but all rats given 2,5-hexanedione (150, 225, 350 mg/kg) survived a 4-wk study period, even though gait changes were evident in the 225 and 350 mg/kg dosage groups by 3 wk. Neither hens nor rats dosed with 2,5 hexanedione for 3 wk had significant neuropathic lesions, although the hens showed dose-related ataxia, weakness, and depression. Early neurofilamentous intraaxonal masses in distal levels of selected myelinated tracts were seen in rats given the high dose of 2,5-hexanedione for an additional week. These studies suggest that hens are sensitive to acrylamide and 2,5-hexanedione toxicities, and that the rat is more likely than the hen to develop neuropathological lesions. PMID- 8345531 TI - Direct measurement of fast axonal organelle transport in the sciatic nerve of rats treated with acrylamide. AB - The effects of acrylamide on fast axonal transport have been measured primarily using the indirect methods of isotope or enzyme accumulation. We report the first direct evaluation of the effects of subchronic acrylamide dosing (150, 300, or 500 mg/kg total dose, i.e., 50 mg/kg, 2x/wk, for 1.5, 3, 5 wk, respectively) on the fast axonal transport motility machinery itself using video-enhanced differential interference contrast optics with digital image processing and computer analysis. Four principle observations were made: (1) Rapid anterograde transport was not affected at any dosage level within 1 wk after cessation of dosing. (2) A high cumulative dosage (500 mg/kg total) of acrylamide or bisacrylamide produced approximately 7-18% decrease in the rate of retrograde transport in both myelinated and unmyelinated axons. (3) Lower dosages of acrylamide (150 or 300 mg/kg total) produced an increase in retrograde transport rates in myelinated axons only. (4) During the "recovery" phase for the 500 mg/kg acrylamide animals (i.e., 3 or 5 wk after the last dosage of acrylamide) the rate of anterograde transport in the myelinated axons was decreased at 3 wk but not at 5 wk, and the rate of retrograde transport in the myelinated axons returned to control levels while the retrograde transport in the unmyelinated axons continued at abnormally slow speeds. The application of this new technique to evaluate the neurotoxic effects of acrylamide provides evidence of dynamic changes in the axonal transport motility machinery itself and differential effects on myelinated versus unmyelinated fibers. PMID- 8345532 TI - Neurotoxicity of glycidamide, an acrylamide metabolite, following intraperitoneal injections in rats. AB - Acrylamide (2-propenamide) monomer produces central-peripheral distal axonopathy in humans and some animal species. Its neurotoxicity is characterized by abnormal sensation, decreased motor strength, and ataxia. Acrylamide forms adducts with glutathione, proteins, and DNA. Recent studies demonstrated that acrylamide is metabolized to its epoxide, glycidamide (2,3-epoxy-1-propanamide). We studied the neurotoxicity potential of glycidamide in male Sprague-Dawley rats. Animals (groups of 6) were injected ip daily with either aqueous acrylamide or glycidamide at an acrylamide-equivalent dose of 50 mg/kg (0.70 mmol/kg). Both treatments resulted initially in the rats circling, which was followed by the onset of ataxia at 7-9 d and hindlimb paralysis at 12-14 d. Treated animals showed muscle wasting. At termination, acrylamide- and glycidamide-treated rats weighed 105% and 86% of initial weight, respectively, compared to 145% for controls. Animals were anesthetized and perfused with 10% neutral phosphate buffered formalin 12 or 14 d after beginning of treatment. Both treatment groups exhibited similar neuropathologic changes in the central and peripheral nervous systems. More severe lesions were produced by glycidamide. A marked increase in the number of affected Purkinje cells in the cerebellum, which exhibited changes ranging from pyknosis to cell death, were present. The brainstem exhibited axonal degeneration with chromatolytic necrosis in midbrain medial and lateral reticular nuclei. The spinal cord was characterized by spongy form changes with vacuoles of different sizes in various levels. These results suggest that glycidamide is an active neurotoxic metabolite of acrylamide. PMID- 8345534 TI - Whole-body exposures to a phosphoric acids aerosol: II. Food/water/weight effects in wild rodent and avian species. AB - Separate inhalation-chamber studies were conducted to assess acute/subacute food intake (g), water intake (ml), and body weight (g) effects of four whole-body phosphoric-acids-aerosol exposures in black-tailed prairie dogs (Cynomys ludovicianus); subacute effects of two exposures were studied in rock doves (Columba livia). A 95% red phosphorus/5% butyl rubber (RP/BR) mixture was burned to produce the aerosol. Each study involved (1) 3 RP/BR target concentration groups (0.0, 1.0, and 4.0 mg/L), (2) 24 prairie dogs or doves (8/group), with gender included as a factor in each study, and (3) a successive 3-phase paradigm (2 d preexposure; 4 and 2 d of approximately 80 min/d exposures to RP/BR for prairie dogs and rock doves, respectively; and 6 d postexposure). Results showed that in-chamber atmospheres were uniform and acceptable for all exposures. No prairie dogs died, but 1 male rock dove died on d 3 postexposure to 4.0 mg/L aerosol. Concentration and gender main effects were significant for the acute (2 h out-of-chamber) food intake, water intake, and weight change of prairie dogs, with aerosol-exposed and male rodents showing decrements. Gender and day main effects were also significant for the subacute (23 h/d) variables in prairie dogs; females weighted less than males, and reduced food/water/weight was evident for all animals during the 4 exposure days and first 3 postexposure days. For rock doves, subacute gender and day main effects, plus concentration x day and concentration x gender x day interactions, characterized the data. A transitive relationship was evident among RP/BR aerosol conditions (0.0 < 1.0 < 4.0 mg/L) and mean decreased food intakes on the exposure days (d2 < d1). Enhanced postexposure water replenishment by female versus male doves exposed to 4.0 mg/L RP/BR aerosol was a main finding. Results are explained based upon a temporal model of phosphoric acid caused ulcers/edema. Effects are compared to prior evidence for albino rats, prairie dogs and rock doves; these are also discussed relative to certain human health and ecotoxicological literature. PMID- 8345533 TI - Neurobehavioral testing of subjects exposed residentially to groundwater contaminated from an aluminum die-casting plant and local referents. AB - Residents adjoining a die-casting plant had excessive headaches, numbness of hands and feet, dizziness, blurred vision, staggering, sweating, abnormal heart rhythm, and depression, which led to measurements of neurobehavioral performance, affective status, and the frequency of symptoms. They had all been exposed via well water and proximity to the plant to volatile organic chemicals (VOC) and to polychlorinated biphenyls (PCBs). The 117 exposed women and men and 46 unexposed referents were studied together for simple and choice visual reaction time, body sway speed, blink reflex latency, color discrimination, Culture Fair (a nonverbal nonarithmetic intelligence test), recall of stories, figures, and numbers, cognitive and psychomotor control (slotted pegboard and trail making A and B), long-term memory, profile of mood states (POMS), and scores and frequencies of 34 symptoms. Choice reaction time, sway speed, and blink latency were impaired in both sexes of the exposed group and trail making B was impaired in exposed women. The POMS scores and frequencies of 30 of 34 symptoms were elevated in both sexes, compared to referents. Recall, long-term memory, psychomotor speed, and other cognitive function tests were reduced in exposed subjects and in the referents as compared to national referents. Neurophysiological impairment, and cognitive and psychomotor dysfunction and affective disorders, especially depression and excessive frequency of symptoms, were associated with the use of wells contaminated with VOCs, TCE and PCBs. PMID- 8345535 TI - Distribution of radioisotopic beryllium in mice after administration by various routes of injection. AB - A 7BeCl2 solution containing 0.5 micrograms Be per mouse was injected subcutaneously, intraperitoneally, intramuscularly, intrathoracically, and intravenously, and distribution was observed for periods up to 1 wk. 7Be was excreted more rapidly following intravenous injection than by the other routes of injection. The amount of Be found in the liver or the spleen was substantial at 1 d after intraperitoneal injection. It increased more in the spleen at 7 d after either intraperitoneal or intrathoracic injection. On the other hand, the amounts of Be stayed almost constant in the kidneys, by the various routes of injection. When injected intrathoracically, the amounts of Be in the heart and the lung were greater than when administered by the other routes of injection. The amounts of Be in the femurs of mice administered by these routes of injection, except with intravenous injection, were greater than in the other organs. The percentage of 7Be in the mineralized bone was 90% of that of 7Be in the femurs when injected intraperitoneally or intrathoracically. However, the ratio of Be in the mineralized bone to that in the bone marrow was 3 to 2. Beryllium had thus a closer affinity for the femurs than for the other organs investigated, with the different modes of administration used. The amount of Be in the entire skeleton was estimated to be substantial. Within the limitations of 1 wk of exposure, the skeleton would appear to be a critical organ. This would suggest that osteosarcomas may occur following administration of Be to laboratory animals for a long-term period. PMID- 8345536 TI - Lack of effect of carcinogen treatment on development of tumors arising spontaneously in Fischer 344 rats. AB - The incidence of a set of neoplasms arising "spontaneously" in Fischer 344 (F344) rats was determined in control and carcinogen-treated animals. Data were obtained from approximately 9000 rats (4000 males and 5000 females) used to study the carcinogenicity of a variety of alkylating compounds, including N-nitroso compounds, azoxyalkanes, and triazenes. In these experiments treated rats and controls were allowed to die naturally and were necropsied, and the tissues were examined histopathologically. The spontaneous neoplasms of interest were mononuclear cell leukemia and neoplasms of the anterior pituitary, adrenal medulla, pancreas, thyroid gland, mammary gland, and testis. These tumors were generally absent from control animals that (rarely) died before 70 wk of age. Although many carcinogen-treated rats died early with treatment-related tumors, a substantial number (1700 males and 2300 females) survived as long as controls. The incidence of spontaneous neoplasms was determined among controls and chemically treated rats at 10-wk intervals from 0 to 140 wk. The incidence of spontaneous tumors was not higher and was frequently statistically lower among treated rats than the corresponding incidence in controls, with the exception of leukemia in female rats. The same result was obtained with the subset of carcinogens not requiring metabolic activation (mostly alkylnitrosoureas). These data indicate that in this rat tumor model system, the alkylating carcinogens, while capable collectively of tumor induction at more than 20 sites, did not accelerate the development of any of the six spontaneously arising solid tumors. This suggests that these spontaneous tumors might arise by a mechanism that is unresponsive to the actions of the alkylating carcinogens. PMID- 8345537 TI - Differences between genetic stocks of chickens in response to acute and delayed effects of an organophosphorus compound. AB - The influence of genotypes of the major histocompatibility complex (MHC) on susceptibility to acute and delayed effects of an organophosphorus ester was measured in adult White Leghorn chickens from lines differing in response to sheep red blood cell (SRBC) antigen. Chickens from lines selected for high (HA) or low (LA) antibody response to SRBC and homozygous for B13B13 or B21B21 genotypes at the MHC were administered a single subcutaneous injection of diisopropyl phosphorofluoridate (DFP) at dosages of 0, 0.25, 0.50, or 1.0 mg/kg body weight using corn oil as the carrier. Criteria for toxicological responses included clinical, biochemical, and pathological measures. Clinical signs of acute cholinergic poisoning and delayed neuropathy were dose related. Brain and blood cholinesterase and carboxylesterase activities were more sensitive to inhibition by DFP than were liver cholinesterase and carboxylesterase activities. Cholinergic signs 3 h after administration of DFP were more pronounced in line HA than in line LA chickens. Pathological evidence of delayed neuropathy 2 wk after DFP administration was also more evident in HA than LA chickens. Although less pronounced than that for lines, differences in neurotoxic manifestations following DFP administration were greater for chickens of B21B21 than B13B13 genotypes. Activity of A-esterases, which hydrolyze organophosphorus esters without being inhibited by them, was lower in plasma of line HA than line LA chickens. Differences among the genotypes in activity of other esterases were not found in chickens not receiving DFP. These results indicated that responses of chickens to the neurotoxicant DFP were influenced by the background genome of the chickens. PMID- 8345538 TI - HIV, breast-feeding and under-5 mortality: modelling the impact of policy decisions for or against breast-feeding. AB - A computer model was developed to assess the impact on under-5 child mortality of breast-feeding practices in developing countries in the context of HIV infection. The model was used to estimate the effect on mortality of cessation of breast feeding among mothers HIV-positive and mothers HIV-negative at birth, for both urban and rural settings. Using parameter values for a hypothetical East African country, cessation of breast-feeding in urban areas was predicted to result in increases in under-5 mortality of 108% for children of mothers HIV-negative at birth, and 27% for those HIV-positive at birth, with slightly larger increases in rural areas, suggesting that breast-feeding should continue to be promoted. A sensitivity analysis was conducted to identify critical values of key variables for which a review of policies encouraging breast-feeding is indicated. This showed that, even under extreme assumptions, cessation of breast-feeding among mothers HIV-negative at birth (but at risk of acquiring HIV during the lactation period) would increase under-5 mortality. For mothers HIV-positive at birth, the key variables are the additional risk of vertical transmission attributable to breast-feeding, the under-5 mortality rate (U5MR) in breast-fed children, and the relative risk of mortality in non-breast-fed compared to breast-fed children. Depending on the values of these key variables, there may be some urban populations with low U5MR in which the positive and negative effects on under-5 mortality of a policy change are finely balanced. However, no change in policy should be made in these areas until more precise information is available on the key variables, and the many adverse consequences of such a change have been fully explored. PMID- 8345539 TI - Clinical spectrum of pulmonary hydatidosis and raised serum IgE levels in the Indian southern peninsula. AB - Fifteen patients with surgically proven hydatid disease of the lung aged between 4 and 51 years were studied. The disease spectrum varied from single to multiple cysts of different sizes, with associated pyogenic chest infections or parasitic infestations of the gut. The serum IgE level varied widely in these cases and very high levels were found in 60% of the patients. This high IgE response was related to the vitality of the cysts, associated bacterial infection of the chest, infection with helminths and smoking habit. PMID- 8345540 TI - Surgical services and training in the context of national health care policy: the Malawi experience. AB - Malawi has a pyramidal health care structure, featuring at its broad base health centres and outreach stations in villages and rural areas; at the middle the district hospitals which receive cases from the villages and outreach health stations, and at its narrow apex the few central hospitals one of which is located in each of the three regions as a referral centre. Primary health care is practised at the health centres mostly by paramedical workers. The district hospitals are manned by general duty doctors and the central hospitals by specialists. Medical auxiliaries (clinical officers and medical assistants) play a vital role in the surgical and anaesthetic services of Malawi. Surgical education is community based and aims at providing staff for the various tiers of the health care pyramid, the surgical training being now jointly supervised by both government and non-government organizations and the new College of Medicine of Malawi. The internship programme is designed to prepare doctors for service in the districts where the bulk of their clinical hospital duties is of a surgical nature. PMID- 8345541 TI - Prevalence of HIV-1 infection in a rural medical clinic in Haiti. AB - To estimate the prevalence of the human immunodeficiency virus type 1 (HIV-1) among the patients attending the out-patient Medicine Clinic of the Hopital Albert Schweitzer in Haiti, the serum samples of 535 consecutive patients were examined for HIV-1 antibodies by enzyme immunoassay. One hundred and twelve sera (20.9%) tested positive (19.3% of the in-district patients and 27.6% of the out district patients). We concluded that HIV-1 infection has already spread to rural areas in Haiti and that we should prepare ourselves for the impact that the increasing number of infected patients will have. PMID- 8345542 TI - Impact of Schistosoma haematobium infection and of praziquantel treatment on anaemia of primary school children in Bertoua, Cameroon. AB - There is some debate as to the extent to which Schistosoma haematobium haematuria may be the cause of anaemia. Our goal was to evaluate the impact of a single 40 mg kg-1 dose of praziquantel on anaemia. Since praziquantel does not reduce the hookworm intensity of infection (a major cause of anaemia in children in the area) changes in the prevalence of anaemia in the study population should be due only to the elimination of S. haematobium. Seven hundred and seventy-one primary schoolboys from Bertoua (East Cameroon) were divided into four groups: high infection, moderate infection treated with praziquantel or placebo, and non infected. Haemoglobin concentrations of the children were determined at the onset of the study and 6 months after the praziquantel intervention. Mean haemoglobin concentrations were not significantly different for no infection or for mild or heavy infection by S. haematobium. A factorial analysis of variance using S. haematobium intensity of infection, malaria and intestinal parasite infections and age as independent variables and haemoglobin concentration as the dependent variable show that only age and malaria infection show a significant relationship with haemoglobin concentration. Despite treatment with praziquantel, all the children in the treatment groups had lower mean haemoglobins 6 months after intervention. A factorial analysis of variance using age, malaria infection and the treatment category as independent variables and the difference in haemoglobin concentration as the dependent variable shows that only malaria infection showed a significant relationship with haemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345543 TI - Childhood infections in Nigeria: an autopsy study. AB - Infections are the leading cause of childhood morbidity and mortality in developing countries. Bronchopneumonia, meningitis and gastroenteritis are the commonest fatal infections encountered in Ibadan. Tuberculous lymphadenitis, bronchopneumonia and meningitis are other frequent causes of death. The predominant sequela of measles is respiratory tract infection. Another important cause of childhood mortality is cerebral malaria. In half of the cases of tetanus no obvious portal of entry can be found. It is advocated that the implementation of immunization schedules should be vigorously pursued to curtail childhood mortality resulting from infection. PMID- 8345544 TI - Assessment of the response in vivo and in vitro of Plasmodium falciparum to sulphadoxine-pyrimethamine in the malarious areas of Iran. AB - Studies of drug resistance of Plasmodium falciparum cases from SE Iran were carried out in vivo and in vitro during 1990-91. In a study of 26 chloroquine resistant infections, using amodiaquine (25 mg kg-1 over 3 days), followed by two thirds of the standard dose of sulphadoxine-pyrimethamine, six cases were resistant at the RI(3) and RII(3) levels. An additional study testing the standard dose of sulphadoxine-pyrimethamine in 43 chloroquine-resistant cases revealed five (11.6%) resistant at the RI(2) and RII(3) levels. Six of the above resistant infections were contracted in Hormozgan, three in Sistan-Baluchestan, one in Kerman provinces of Iran and one in Pakistan. In five of 22 successful in vitro tests, carried out on different isolates, the parasites grew to schizonts (> or = 8 nuclei) in the wells containing 1000 pmol sulphadoxine and 12.5 pmol pyrimethamine, indicative of resistance. PMID- 8345545 TI - Ophthalmomyiasis in Kuwait: first report of infections due to the larvae of Oestrus ovis before and after the Gulf conflict. AB - We report for the first time four cases of ophthalmomyiasis due to the larvae of Oestrus ovis in Kuwait, before and after Operations Desert Shield and Desert Storm. The larvae were easily removed under local anaesthetic. The symptom complex of acute foreign body sensation, irritation, redness, lacrimation and photophobia resolved rapidly. Ophthalmic antibiotic and corticosteroid drops were also instilled and recovery was uneventful. The ophthalmomyiasis may not always be associated with contact with sheep-rearing per se. Medical personnel should therefore be aware that in cases of what might appear initially as acute, non specific catarrhal conjunctivitis, patients with the persistent symptom complex should be re-examined to exclude ophthalmomyiasis due to the larvae of O. ovis in endemic areas. PMID- 8345546 TI - Improved method for the concentration and purification of faecal cysts of Entamoeba histolytica for use as antigen. AB - Human stool samples are the most widely used source of E. histolytica cysts for diagnosis and research. Cysts concentrated from faecal samples are contaminated with faecal debris and bacteria and are unsuitable for use as antigens. Other gradient purification and sedimentation procedures result in considerable cyst losses. We present an effective and simple purification procedure using varying densities of Percoll that yields an adequate cyst concentration from a moderate cyst load in a single stool sample. PMID- 8345548 TI - Brain echinococcal disease in Pondicherry. AB - A 29-year-old man, a vegetarian, agriculturist and resident of a village near Pondicherry, presented with focal seizures with secondary generalization. EEG showed a right frontoparietal focus, the blood eosinophil count was 25%, the indirect haemagglutination titre was more than 1:2048 for Echinococcus protein and Casoni's skin test was strongly positive, the CT scan showed an isolated rounded lesion in the right frontoparietal area partially enhanced with contrast media. He was subjected to surgery with complete removal of the cyst which confirmed the diagnosis of echinococcal disease of the brain. Post operatively he took only anticonvulsant drugs and was free of seizures during the two-year post operative follow-up period. The CT scan is a superior neurodiagnostic tool to blood serological tests in the diagnosis of brain echinococcal disease. PMID- 8345547 TI - A study of placentas from Wuchereria bancrofti microfilaraemic and amicrofilaraemic mothers. AB - The prevalence of transplacental transfer of microfilariae and structural lesions in the placentas of amicrofilaraemic (n = 10) and Wuchereria bancrofti microfilaraemic (n = 10) pregnant women from the prenatal care unit of the Hospital das Clinicas, Recife, Brazil, was investigated. Study participants were selected by filtration (3 microns/13 mm) of nocturnal (2300-0100 h) venous blood. A detailed histopathological examination was performed to detect abnormalities in the placenta, the cord and the foetal membranes. Both study groups had similar obstetric profiles. Parasitaemia was present during labour in nine of ten microfilaraemic women, but no microfilariae were found by filtration of 5-10 ml cord blood. No macroscopic abnormalities were seen in placentas from microfilaraemic mothers; two placentas from the amicrofilaraemic cases contained, respectively, infarcted areas and cysts at the cut surface. Microscopy failed to detect microfilariae in the intervillous spaces, chorionic and decidual vessels, or the umbilical cord. Thus, transplacental transfer of Wuchereria bancrofti microfilariae seems to be a rare phenomenon, and microfilaraemia does not appear to be a risk factor for placental pathology. PMID- 8345550 TI - Sonography of fetal midgut herniation: normal size criteria and correlation with crown-rump length. AB - Forty-eight fetuses were prospectively evaluated to (1) determine the normal size range of herniated midgut and (2) correlate sonographically the timing of midgut herniation with CRL. All fetuses of CRL 38 mm or less, and two of six fetuses with a CRL of 40 to 42 mm, demonstrated midgut herniation. No fetuses with a CRL greater than 44 mm had this finding. The cord containing midgut increased roughly from 4 to 7 mm, in maximum dimensions, for CRL of 19 to 41 mm. An anterior abdominal wall mass greater than 7 mm at any CRL, or of any size in a fetus of CRL greater than 44 mm, is suggestive of a fetal anomaly. Alternatively, a cord base "mass" within the 4 to 7 mm range for a CRL of 19 to 44 mm can be considered normal and not to require any follow-up. PMID- 8345549 TI - Protocol for out-patient management of dengue illness in young adults. AB - A prospective study on the practicality of an out-patient management protocol for dengue infection in adults was carried out during a 2-month period. Doctors were requested to follow the protocol and assessment was done on the patients' outcome, the admission rate, and the compliance to the protocol by doctors and patients. One hundred and sixty-two patients (mean age 27.3 years) were clinically diagnosed to have dengue illness. Among them, 82.7% had dengue fever (DF); 13.0% had dengue haemorrhagic fever (DHF) and 4.3% had dengue shock syndrome (DSS). Dengue aetiology was confirmed in 69.4% of the DF group and 85.7% of the DHF and DSS groups. There were no deaths among the 162 patients. The admission rate was 43.8%. A high compliance rate of 86.4% by the doctors and a low patient default rate of 16.4% showed that the protocol was practical. PMID- 8345551 TI - Pretreatment sonographic evaluation of inguinal lymph nodes in patients with vulvar malignancy. AB - The state of the inguinal nodes is a major prognostic factor in vulvar carcinoma. Because of new surgical trends with selective inguinal lymphadenectomy, the preoperative evaluation of inguinal lymph nodes is essential for adequate treatment of vulvar carcinoma. To evaluate the adequacy of clinical examination and high-frequency transducer sonography in detecting metastatic inguinal lymph nodes, we studied 25 patients with vulvar malignancy who underwent operation. Histopathologically proved lymph node metastases were found in 11 (22%) of 50 inguinal areas studied. All of the suspected metastases were in patients with stage III-IV disease. The inguinal lymph node metastases were found by sonography in nine (82%), by preoperative palpation in one (9%), and by operative palpation in six (55%) of 11 areas. The difference between sonography and palpation was statistically significant (P < 0.01). The sensitivity and specificity were 82% and 87% for sonography, 9% and 100% for preoperative palpation, and 55% and 90% for operative palpation. PMID- 8345552 TI - Duplex ultrasonography of superior mesenteric artery: interobserver variability. AB - The aim of this study was to evaluate the interobserver variability during duplex ultrasonographic investigation of the SMA. Eleven healthy volunteers were examined twice under the same conditions by two independent observers. Three basic Doppler wave parameters were assessed for the SMA: pV, edV, and rT. The tD was recorded for SMA and abdominal aorta (AotD) with B-mode imaging. The interobserver variability was very low for all parameters: pV = 13.5 cm/s; edV = 3.4 cm/s; rT = 0.01 s; tD = 0.3 mm; AotD = 0.5 mm, with corresponding 95% confidence intervals as follows: pV = 19 cm/s; edV = 4.7 cm/s; rT = 0.015 s; tD = 0.4 mm; and AotD = 0.75 mm. Coefficients of variation also showed very low dispersion for results obtained. Under the appropriate standard conditions for duplex sonographic examination of the mesenteric artery, assessments of basic Doppler wave parameters do not differ significantly between independent investigators. Reliable evaluation of B-mode distances can be obtained by replication of measurements. PMID- 8345553 TI - Nomograms of the fetal lateral ventricles using transvaginal sonography. AB - Nomograms of the fetal lateral ventricles were obtained by the transvaginal approach. Three hundred low-risk women with no sonographically apparent fetal anomalies were scanned prospectively in a cross-sectional study. Three measurements in the parasagittal plane, three in the midline coronal plane, and two in the posterior coronal plane were used to generate seven nomograms. Two additional nomograms reflecting two calculated ratios also were created. A mean regression line and the 5th and 95th confidence intervals were determined. We concluded that transvaginal sonography of the fetal brain generates images of both hemispheres of good enough resolution to allow several precise and reproducible measurements. PMID- 8345554 TI - Fetal growth: a comparison of growth curves with mathematical modeling. AB - This study compared the use of fetal growth curves with the Rossavik mathematical model in predicting third trimester fetal growth in 27 Hispanic patients. The parameters tested were BPD, HC, AC, and FL. The growth curve method of predicting third trimester fetal growth was significantly more accurate than the mathematical model for three of the four fetal parameters tested: BPD, HC, and FL. We conclude that the mathematical model method offered no advantage over the more commonly used growth curve method for predicting third trimester fetal growth. In addition, growth curves do not require complex calculations and are conceptually simpler and easier to use. PMID- 8345555 TI - Ultrasonographic evaluation of the endometrium and correlation with endometrial sampling in postmenopausal patients treated with tamoxifen. AB - Seventy-two asymptomatic, postmenopausal women treated with tamoxifen for breast cancer were studied prospectively with vaginal ultrasonography, followed by endometrial sampling. Seventy-one patients demonstrated an endometrial echo of more than 5 mm, and one displayed an endometrial echo of less than 5 mm. No patient with an endometrial echo of less than 5 mm displayed any endometrial pathology. Different endometrial pathologic conditions were found when the endometrial echo was over 5 mm. When classifying those patients whose ultrasonic endometrial widths were wider than 5 mm, on the basis of different endometrial histologic findings, no obvious correlation was found between the various pathologic endometrial findings and endometrial thickness. Thus, a "thicker" endometrial sonographic image did not necessarily correlate with pathologic endometrial findings. When ultrasonic endometrial thickness of 5 mm was considered the upper limit of normal, the sensitivity of ultrasonography in correlating to positive histologic findings was 91% and the specificity was 96%. These findings suggest that there is good correlation between endometrial width measured by ultrasonographic assessment and histologic findings. PMID- 8345556 TI - Fetal Doppler echocardiography in pulmonary atresia. AB - The prenatal diagnosis of pulmonary atresia is of particular importance because the affected neonate may be dependent on ductal blood flow to the lung, requiring urgent administration of prostaglandins. We review eight cases studied by ultrasonography in utero. Severe tricuspid regurgitation was present in six fetuses. Right ventricular size varied among cases. Right atrial enlargement was present in seven, usually with tricuspid regurgitation. Failure to identify the main pulmonary artery or valve on a single examination was not specific. Doppler flow studies were most reliable for the diagnosis by establishing the existence of retrograde flow in the ductus arteriosus from the aorta. PMID- 8345557 TI - Sonographic heat generation in vivo in the gravid long-tailed macaque (Macaca fascicularis). AB - Temperature elevations that occur during diagnostic ultrasonic exposure were assessed in vivo in gravid macaques after 10, 20, or 30 min (scan mode; N = 30) or 5, 10, or 15 min (pulsed Doppler; N = 32). Five time points were assessed during the second and third trimesters (gestational days 70 to 150 +/- 2; term, approximately 165 days) using a transient thermocouple technique. Measurements were obtained intracranially or at the muscle-bone interface using a commercial sector scanner (ATL MK 600, 7.5 MHz scanhead; scan mode, ISPTA) = 27 mW/cm2, ISPPA = 85 W/cm2, pulse repetition frequency (PRF) = 1 kHz; pulsed Doppler - ISPTA = 54 mW/cm2, ISPPA = 1.5 W/cm2, PRF = 18.5 kHz). Overall, the greatest temperature elevation achieved with either modality or location was 0.6 degrees C. PMID- 8345558 TI - Preoperative sonographic diagnosis of gallbladder torsion: report of two cases. PMID- 8345559 TI - Sonographic diagnosis of traumatic gallbladder avulsion. PMID- 8345560 TI - Prenatal diagnosis of cerebral neuroblastoma by fetal brain biopsy. PMID- 8345561 TI - Doppler sonographic detection of reverse twin-twin transfusion after intrauterine death of the donor. AB - We report a "stuck" twin, in which a reverse blood shunt from the recipient to the donor was detected by Doppler sonography after death of the donor. This acute reverse transfusion caused intrauterine fetal distress and severe neonatal anemia of the surviving recipient. We believe that acute hemodynamic change after death of one fetus, in addition to causing a derangement in coagulation, causes immediate danger or subsequent organ damage for the surviving co-twin. PMID- 8345562 TI - Pharmacokinetics of single intravenous and single and multiple dose oral administration of rifampin in mares. AB - The disposition of rifampin in six healthy mares after single intravenous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/kg administered twice a day was investigated using a high performance liquid chromatographic (HPLC) method. Pharmacokinetic variables for rifampin determined using the HPLC method were comparable to variables reported from earlier studies utilizing a microbiological assay. Desascetylrifampin, a major metabolite of the parent compound, could not be detected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin increased from the first to the second dose of the multiple dose oral study and then remained unchanged through 72 h. At 84 h after the first dose (i.e. 12 h after the final dose) the rifampin concentration was significantly decreased (P = 0.001). The harmonic mean of the half-life of rifampin decreased significantly from 13.3 h after a single oral dose of 7.99 h after the seventh oral dose. The mean serum protein binding of rifampin over the concentration range of 2-20 micrograms/ml was 78%. Mean trough serum concentrations of unbound rifampin after multiple oral doses ranged from 0.67 micrograms/ml at 24 h to 0.40 micrograms/ml at 72 h. The mean unbound serum rifampin concentration at 84 h (i.e., 12 h after the final dose) was 0.30 micrograms/ml. Trough concentrations and the 84-h sample concentration of unbound rifampin exceeded the minimum inhibitory concentration for most gram positive bacterial isolates from horses reported in this study. All organisms with minimum inhibitory concentrations less than 0.125 micrograms/ml were considered susceptible. Based on the pharmacokinetics of rifampin after p.o. administration, we concur with the current dosage recommendation of 10 mg/kg twice a day by mouth. At this dose, most streptococci, Rhodococcus equi, and coagulase-positive staphylococci would be considered susceptible to rifampin. PMID- 8345563 TI - Biliary secretion and enterohepatic recycling of fenbendazole metabolites in sheep. AB - Fenbendazole (FBZ) was administered intraruminally at 5.0 mg/kg, containing a trace of [14C]-FBZ, to sheep fitted with a permanent bile duct cannula and the behaviour of FBZ and its metabolites examined in bile and plasma. Of the administered radiolabelled dose, 47% was secreted in bile of which 34% was accounted for as conjugated and 4% as unconjugated (free) metabolites. Hydroxylated oxfendazole (OH.OFZ) was the major biliary metabolite contributing 66%, and hydroxy-FBZ (OH.FBZ) 27%, of the total metabolites characterized. Small amounts of OFZ and hydroxy FBZ sulphone (OH.FBZ.SO2) were also present in bile. The rapid appearance of OH.OFZ in bile, even before maximum concentrations of OFZ occurred in plasma, indicated that sulphoxidation and hydroxylation was the major route of FBZ metabolism. Following intraduodenal infusion of free biliary metabolites, FBZ and its metabolites rapidly appeared in bile indicating absorption from the small intestine. When conjugated metabolites were infused they continued to appear in bile for a further 15-20 h after cessation of infusion indicating that absorption of hydroxylated metabolites occurred largely after bacterial deconjugation in the large intestine. Approximately 40% of biliary metabolites were estimated to undergo enterohepatic reabsorption but they contributed minimally to the metabolite content in plasma. It is suggested that during the process of recycling-biliary metabolites make substantial contact with parasites in the mucosa of the small and large intestine thereby contributing to the anti-helminthic activity of FBZ. PMID- 8345564 TI - The effect of age on phenylbutazone pharmacokinetics, metabolism and plasma protein binding in goats. AB - Phenylbutazone (PBZ) was administered intravenously as a single dose (10 mg/kg) to adult male and 1-day-, 10-day-, 4-week- and 6 week-old male goats. The plasma concentration of PBZ and its major metabolites oxyphenbutazone (OPBZ) and gamma hydroxyphenbutazone (gamma-OHPBZ) was measured over time. The elimination half life (t 1/2 beta) of PBZ decreased from 120 h in the 1-day-old to 16 h in the adult goats. Although the volume of distribution (Vd) did not change significantly during maturation, the total body clearance (Cl B) increased from 2 ml.h-1.kg-1 in 1-day-old to 13 ml.h-1.kg-1 in the adult goats; the increase was 2 fold in the first 10 days of life. Oxyphenbutazone was detectable in the plasma of adult and 6-week-old goats as early as 15 min after PBZ administration. Its peak concentration occurred at 1.5 h (1.6 micrograms/ml) in adults and at 6 h (0.95 micrograms/ml) and 12 h (0.36 micrograms/ml) in 6- and 4-week-old goats respectively. The highest plasma concentration of gamma-OHPBZ was achieved in 4 week-old followed by 6-week-old and adult animals. PMID- 8345565 TI - The postnatal development of drug-metabolizing enzymes in hepatic, pulmonary and renal tissues of the goat. AB - It is important to study the development of drug biotransformation enzymes, because from a pharmacological and therapeutic point of view these enzymes are responsible for eliminating most drugs. Their concentration at each age is critical when deciding the dose regimen, particularly in the neonates who are deficient or have very low levels of these enzymes. From a toxicological perspective, the role of these enzymes varies, with some of them being directly responsible for activation of certain chemicals to reactive intermediates with deleterious consequences to the animal. The time course of appearance of these enzymes throughout the life of the animal could be depicted from the study of their ontogeny and therefore the prediction of when the animal would be at risk should be possible. Experiments were designed to measure in vitro, the activity of drug-metabolizing enzymes in liver, lung and kidney of newborn, 1-week-, 4 week and 6-week-old and adult goats. The microsomal monoxygenase activities were measured utilizing substrates designed to characterize the development of the cytochrome P450 (P450). For phase II enzymes, the activity of UDP glucuronyltransferase towards 1-naphthol and p-nitrophenol was measured in addition to the cytosolic glutathione S-transferase activity towards, 1,2 dichloro 3-nitrobenzene. The results indicated that the newborn goat tissues exhibited very low activity of drug-metabolizing capacity in all pathways studied. These activities increased to the adult values by 6 weeks of age. In general, the development of the mono-oxygenase activities followed the same pattern as the overall P450. The UDP-glucuronyltransferase activity towards both substrates was deficient at birth and surged to above adult values by the first week of age. The toxicologic and pharmacologic implication of the development of these enzyme activities are discussed. PMID- 8345566 TI - Effect of gonadal hormones on the plasma clearance and metabolite formation of antipyrine in the dwarf goat. AB - The effect of gonadal hormones on the plasma elimination and urinary metabolite profile of antipyrine was studied in dwarf goats. Female goats were treated with testosterone and male goats were treated with 17 beta-oestradiol. Castrated males were treated with either testosterone or 17 beta-oestradiol. Antipyrine (25 mg/kg, i.v.) was given both before and after the hormonal treatments. The effects of the hormonal status on the plasma elimination of the parent compound were not consistent. This was possibly due to the fact that formation of the main metabolite of antipyrine in the goat, 4-hydroxy antipyrine (OHA), was not affected by sex or hormonal treatment. On the other hand, there were clear effects of hormonal status on urinary excretion of the three other metabolites. In females and castrated males testosterone suppressed the formation of norantipyrine (NORA), 3-hydroxymethylantipyrine (HMA) and 4,4' dihydroxyantipyrine (DOHA). Intact males produced smaller amounts of these metabolites than females. It is concluded that distinct xenobiotic metabolizing pathways exist in the dwarf goat, which are influenced in their activity by gonadal hormones. This confirms previous findings in rats and mice. The possibility that sex hormones influence drug metabolism in food-producing animals could have consequences for veterinary therapeutics and public health. This study also demonstrates that, when using the antipyrine test for the assessment of hepatic drug metabolism, it is very important to include the determination of metabolites. PMID- 8345567 TI - Percutaneous absorption of organophosphorus insecticides in pigs--the influence of different vehicles. AB - In 40 experiments on 20 pigs three different organophosphorus insecticides (OPs), parathion (n = 6), phoxim (n = 7) and phosmet (n = 7), were administered both intravenously (i.v.) and dermally (d.) as 'pour-ons' in a crossover design in order to determine the dermal bioavailability of the OPs. As percutaneous absorption of drugs may be affected by the vehicle used, three chemically different vehicles--DMSO, 1-octanol and macrogol 400-were used for the dermal administration of each of the OPs. The pharmacokinetic parameters measured showed that 15-30% of dermally applied parathion is absorbed when administered in DMSO or octanol, but only 4-5% when administered in macrogol. Absorption was fastest with DMSO and slowest with macrogol. For the two ectoparasiticides, phoxim and phosmet, only between 0.5 and 3% of the dermal dose was absorbed with little difference in the absorption rate between the three vehicles. On the basis of the very limited dermal bioavailability for these two OPs it seems doubtful whether sufficient concentrations can reach the ectoparasites through the systemic route. PMID- 8345568 TI - The pharmacokinetics of flunixin meglumine in the sheep. AB - Flunixin meglumine was administered intravenously and intramuscularly in sheep and the pharmacokinetics of the drug studied. Plasma concentrations of flunixin were measured by high performance liquid chromatography. The decline in plasma flunixin concentration with time was best fitted by a triexponential equation. The pharmacokinetics following intravenous administration of 1.0 mg/kg indicate that flunixin has a rapid distribution half-life (t1/2 pi = 2.3 min), a slow body clearance rate (Clb = 0.6 ml/kg/min) and an elimination half-life of 229 min. Similarly, at 2.0 mg/kg, flunixin is rapidly distributed from the plasma, t1/2 pi = 2.7 min, has a slow body clearance rate (Clb = 0.7 ml/kg/min) and an elimination half-life of 205 min. Following intramuscular injection flunixin is rapidly and well absorbed from the injection site. It had a mean maximum concentration (Cmax) of > or = 5.9 micrograms/ml when administered at a dose rate of 1.1 mg/kg, and a relative bioavailability of 70%. Plasma concentrations increase proportionally to dose over the range 1.1 mg/kg-2.2 mg/kg when administered by the intramuscular route. PMID- 8345569 TI - Oral absorption and bioavailability of fenbendazole in the dog and the effect of concurrent ingestion of food. AB - Fenbendazole was administered orally without food to six beagle dogs at 2.5, 5.0, 10, 20, 40 and 80 mg/kg of body weight. Increasing the dose rate did not significantly increase the amount of fenbendazole absorbed. In a separate study fenbendazole was administered to the same six beagle dogs at a dose rate of 20 mg/kg of bodyweight in food with high, medium and low fat content. The food provided 1.52, 0.70 or 0.34 g of fat per kg of body weight. Administration of fenbendazole in food with different fat contents did not affect its relative bioavailability. Administration of fenbendazole at a dose rate of 20 mg/kg in food, irrespective of fat content, did however significantly increase its bioavailability when compared to administration of the same dose as a bolus on an empty stomach. PMID- 8345570 TI - Effects of age and indomethacin on response and sensitivity of pulmonary artery to phenylephrine and to histamine in pigs. AB - The vasoconstrictor effects of phenylephrine and histamine were investigated in isolated strips of pulmonary arteries in pigs during ageing. Interactions between phenylephrine-induced responses and arachidonic acid derivatives were also studied by incubating the blood-vessels with indomethacin. Potency (pD2 values) and maximal effects (EmaxX) recorded in 5-week-old piglets (group I, n = 5) with phenylephrine [5.71 +/- 0.17 and 0.76 +/- 0.22 g/mg of dry tissue respectively (mean +/- SEM)] were similar to values found in 12-week-old animals (group 2, n = 5) (5.49 +/- 0.30 and 1.06 +/- 0.27 g/mg of dry tissue respectively). The sensitivity and responsiveness of tissues to this agonist were significantly reduced in 26-week-old mature pigs (group 3, n = 6) as indicated by the decrease in pD2 (3.91 +/- 0.23; P < 0.01) and Emax (0.27 +/- 0.13 g/mg of dry tissue; P < 0.05) values observed in this group. Histamine (10(-3) M)-induced maximal responses (Emax) were significantly higher in group 2 (2.23 +/- 0.49 g/mg) than in group 1 (0.85 +/- 0.11 g/mg; P < 0.05) and in group 3 (0.48 +/- 0.10 g/mg; P < 0.01). In 5-week-old animals, indomethacin (3 x 10(-5) M) significantly (P < 0.05) shifted the concentration-response curve to phenylephrine to the right (0.28 log. units) and depressed contractions to this drug as shown by the significant decrease of 39.5% (P < 0.05) in Emax. This cyclo-oxygenase inhibitor had no effect in other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345571 TI - Three phase elimination of oxytetracycline in veal calves; the presence of an extended terminal elimination phase. AB - The pharmacokinetics of oxytetracycline were studied after both intravenous (i.v.) and intramuscular (i.m.) administration to a group of five veal calves. Blood samples were taken frequently during the terminal elimination phase in order to calculate a reliable elimination rate constant. Because of the low limit of quantification of the method of analysis used, oxytetracycline plasma concentrations could be monitored over a 12-day period of time. After the intravenous administration of oxytetracycline, data were fitted according a three compartment model. After i.m. administration, plasma-concentration-time curves could best be described by a two-compartment model. It was demonstrated that a very slow terminal elimination phase was present both after i.v. and i.m. administration with a half-life of approximately 95 h. The data show that this phase cannot be explained by slow absorption from the injection site and that release of oxytetracycline incorporated into bone is not a likely explanation. PMID- 8345572 TI - Pharmacokinetics and anthelmintic efficacy of febantel in the racing pigeon (Columba livia). AB - This paper reports on the pharmacokinetics and the efficacy of febantel against Capillaria obsignata and Ascaridia columbae in the racing pigeon. Febantel was rapidly cleared from the circulation and highly metabolized. The efficacy of febantel against Capillaria and Ascaridia was studied on lightly and heavily infected pigeons. The efficacy against Ascaridia was 100% for the faecal egg count reduction (FECR) as well as for the worm reduction in all treated pigeons. After two treatments with febantel against Capillaria in heavily infected pigeons the FECR amounted to 96.7% and worm reduction was 95%. In order to effectively remove both parasites from the host, repeated treatments with febantel at a short interval could be the treatment of choice. PMID- 8345573 TI - The pharmacokinetics of sulfachlorpyridazine in channel catfish, Ictalurus punctatus. PMID- 8345574 TI - Pharmacokinetics of albendazole, albendazole sulfoxide and netobimin in goats. PMID- 8345575 TI - Pharmacokinetic behaviour of phenylglyoxal bis(guanylhydrazone) (PGBG) after oral administration to rabbits. PMID- 8345576 TI - Comparison of detrusor contractility of guinea pig bladders in situ and strips from these in vitro. AB - To study the relative importance of neurogenic factors in detrusor contractility, active bladder wall stress values were compared in situ and in vitro. Eight male guinea pigs were used. The active stress in the bladder wall in spontaneous micturition contractions was calculated from the results of urodynamic examinations and compared with the active stress developed in response to optimum electrical stimulation in full-thickness bladder wall strips taken from the same bladders. The results indicated that, in normal micturition, the detrusor muscle is not fully stimulated, and the rate of pressure development is not determined by mechanical factors. To identify topological variations of detrusor contractility, the strips were taken from three different locations. It was found that strips from the posterior wall contracted more forcefully than those from the anterior wall. PMID- 8345577 TI - Hormonal regulation of human testicular inhibin alpha and beta B subunit messenger RNAS. AB - Changes in messenger ribonucleic acids (mRNAs) of human testicular inhibin alpha and beta B subunits induced by human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were assessed in vivo and in vitro. After a single administration of hMG, inhibin alpha mRNA in the human testis significantly increased, whereas inhibin beta B mRNA remained unchanged. Administration of hCG induced a slight increase in inhibin alpha mRNA without affecting inhibin beta B mRNA. In experiments in vitro using the testicular organ culture technique, an exposure to hMG for 24 hours induced a dose-related significant increase in inhibin alpha mRNA. Inhibin beta B mRNA was not affected by either hCG or hMG exposure. These results indicate that luteinizing hormone (hCG) as well as follicle stimulating hormone (hMG) may play a role in the regulation of human testicular inhibin alpha mRNA, although the mechanism of the LH action is not clear. PMID- 8345578 TI - Effect of atrial natriuretic peptide on urine flow and glomerular filtration during acute renal allograft rejection. AB - The effect of exogenous atrial natriuretic peptide (ANP) on urine excretion and glomerular filtration rate (GFR) during acute renal allograft rejection was evaluated in a canine model. Eight animals underwent simultaneous allotransplantation and unilateral native nephrectomy. No preoperative or postoperative immunosuppressive therapy was given. Acute renal function studies were performed on the allografts and companion, native kidneys following surgical exposure and mobilization on the third postoperative day. At reexploration, the allografts were found to be grossly enlarged (138 +/- 10 gm.) and contained moderate-to-marked perivascular interstitial infiltration. Glomerular filtration rate, determined by measurement of urinary inulin clearance, was significantly reduced from prenephrectomy baseline values (19 +/- 4 ml. per minute versus 32 +/ 5 ml. per minute, p < .05). During a 30 minute, intravenous ANP infusion, allograft urine flow rates increased from 1.4 +/- 0.5 ml. per minute to 3.3 +/- 0.4 ml. per minute (p < .01), and GFR increased from 19 +/- 4 ml. per minute to 24 +/- 4 ml. per minute (p < .05). During ANP infusion, mean arterial pressure declined from 136 +/- 7 mm. Hg to 116 +/- 7 mm. Hg (p < .05), and the hematocrit remained unchanged. These observations are consistent with previously described, ameliorative effects of ANP in other models of acute ischemic renal injury and provide an experimental basis for more extended studies examining the potential usefulness of ANP as adjunctive therapy in the treatment of acute renal allograft rejection. PMID- 8345579 TI - Plasminogen activators: regulators of tumor cell adherence to sites of lower urinary tract surgical trauma. AB - Tumor cell adherence (TCA) to sites of surgical injury is a requisite step in implantation-mediated tumor recurrence. This study examined the relationship between tumor-associated plasminogen activator (PA) and the ability of tumor cells to remain adherent to surgical injury sites. High (1E8) and low (3A9) PA producing clones from the murine transitional carcinoma cell line 4909 were selected using an in vitro 125I fibrinolysis assay. Net cellular PA activity of each clone was determined from cell lysates using a chromogenic substrate assay. In vitro TCA and fibrin substrate lysis as a function of time were simultaneously measured using a tetrazolium dye assay in combination with an 125I fibrinolysis assay. In vivo TCA to in situ cautery-injured rat bladders was measured 30 minutes (n = 12 animals/cell line) and 24 hours (n = 18 animals/cell line) following tumor exposure with a radiolabeled TCA assay. In vitro and in vivo competitive binding assays evaluated the relative adherence of mixtures of the 1E8 and 3A9 clones. Cellular PA activity was 0.022, 0.014 and 0.007 units per mg. protein for the 1E8, 4909 and 3A9 cell lines. In vitro TCA to fibrin in the presence of plasminogen was significantly different for each cell line and demonstrated an inverse relationship with both plasminogen-dependent fibrin lysis and cellular PA activity (p < 0.0001). The in vivo assay showed that the percentage of 1E8 cells remaining adherent 24 hours after tumor exposure was significantly less than that of the 3A9 cells (p = 0.01). Both in vitro and in vivo competitive binding assays demonstrated preferential adherence of the 3A9 cell line. Cellular PA production appears to be a tumor-intrinsic variable that modulates TCA to surgical injury sites. PMID- 8345580 TI - Events leading to septic death from experimental acute pyelonephritis in the monkey. AB - Experimental acute pyelonephritis in monkeys led to death in some of the animals following renal E. coli inoculation. It was found that both the inflammatory response and cytokine activation were much more severe in these monkeys as compared with others that survived. IL-1 was decreased just before death, and there were early increases in IL-2 and IL-6 serum concentrations, but no significant increase in TNF values. The data suggest that death in sepsis is due in part to excessive cytokine release because of a decrease in the protective activity of IL-1. PMID- 8345581 TI - Subcutaneous port for longterm access and administration of topical chemotherapy to the upper urinary tract. AB - Fourteen silicone pigtail catheters were inserted into the renal pelves of ten 25 kg. pigs. These catheters were connected to injection ports implanted in the flank. Each animal received 15 mg. of thiotepa, into one port, weekly for 8 weeks. These were well tolerated. Percutaneous radiography and histological examination showed effective distribution of thiotepa throughout the upper urinary tract. Microscopic changes included cytoplasmic vacuolation, cystic changes and denudation of the mucosa. There was edema and chronic inflammatory infiltrate in the submucosa. This method of access to the upper tracts should be considered for long-term recurrent treatment of upper tract superficial transitional cell carcinoma. PMID- 8345582 TI - Characterization of a new human bladder cancer cell line, UCRU-BL-28. AB - A new human bladder cancer cell line, UCRU-BL-28 has been established and characterized from a relapsed, cisplatin resistant, grade II, stage T4 tumor. This line is tumorigenic in nude mice and reflects the pathology of the original tumor. The morphology, the expression of tumor-associated antigens and EGF receptors, and the ability to grow both in an anchorage independent manner and in the absence of serum is explored. The BL-28 line has 71-74XXY chromosomes, with del 5q, der(9) and i(19q). Further studies on the molecular basis of bladder cancer, chemosensitivity to cisplatin, growth factor production and tissue invasion are under way. PMID- 8345583 TI - Chromophore enhanced laser welding of canine ureters in vitro using a human protein solder: a preliminary step for laparoscopic tissue welding. AB - Laser welding of the genitourinary tract has the potential advantage of forming an immediate watertight seal. It may obviate the need for sutures, eliminate the inherent lithogenic reaction to suture, and potentially improve healing. In the current study we employed a KTP-532 laser in vitro to weld canine ureters. Ureters were transected over a stent and immediately repaired using the KTP-532 laser (power density 7.14 W/cm.2, spot size = 0.5 cm.) alone or in combination with different tissue solders. Solders consisted of 40% human albumin alone or with the addition of iron oxide or fluorescein as light absorbing dyes (chromophores). Following the repairs, intraluminal bursting strength and the total energy required to complete the repairs were measured. The KTP laser alone was not able to achieve a satisfactory repair. Successful ureteral repairs were achieved in all solder groups while maintaining ureteral continuity at supraphysiologic pressures. PMID- 8345584 TI - Angiotensin II receptors in the rat urinary bladder smooth muscle: type 1 subtype receptors mediate contractile responses. AB - Angiotensin II (Ang II) receptors in the rat urinary bladder smooth muscle were investigated by in vitro responses of smooth muscle strips to exogenous Ang II stimulation and in radioligand binding assays. Ang II (10(-10) M. to 10(-5) M.) caused a potent contractile response in a concentration-dependent manner. Using the recently developed nonpeptide subtype-selective antagonists, the Ang II induced contractile response was further characterized. The Ang II-induced contractile response was inhibited weakly by the type 2 subtype (AT2)-selective antagonist PD123319 but was potently inhibited by the type 1 subtype (AT1) selective antagonist DuP 753 with a pA2 value of 9.03, suggesting that the response is mediated predominantly by AT1 receptors. [125I]Ang II was used to specifically label a single class of binding sites with a dissociation constant of 0.31 nM. and a maximal binding capacity of 41.5 fmol./mg. of protein. DuP 753 could completely antagonize the binding of Ang II in a particulate fraction of rat bladder (Ki = 14 nM), whereas PD123319 did not have any effect in the concentration range of 10(-9) to 10(-5) M. The results suggest that AT1 receptors rather than AT2 receptors predominantly mediate Ang II-induced contraction in the rat urinary bladder. PMID- 8345585 TI - Developmental alterations in the fetal lamb bladder subjected to partial urethral obstruction in utero. AB - To identify the structural changes seen in the developing bladder subjected to outflow obstruction, a fetal lamb model was developed. With this model, which attempts to reproduce conditions such as those found in posterior urethral valves, quantitative biochemical parameters were used to evaluate the effects of partial outflow obstruction on detrusor cellularity and innervation in the developing bladder. Partial urethral obstruction was created in 9 fetal sheep (90 to 100 days gestation), 6 sham operated animals serving as controls. Fetuses were delivered at term and sacrificed. Bladders were removed and weighed. Mucosa free detrusor was assayed for DNA and choline acetyltransferase (ChAT) activity, indices of cell number and cholinergic innervation, respectively. In similar specimens of detrusor, cell ploidy and nuclear size were determined by flow cytometry and nuclear morphometry, respectively. The results showed that partial urethral obstruction in utero resulted in a significant increase in bladder weight (p < 0.05) and total detrusor DNA content (p < 0.01). With the increase in detrusor DNA content, there was a parallel increase in total detrusor ChAT activity. These results suggest that early development of the bladder is altered both on a cellular level (increase in cellularity) and a neural level (increase in cholinergic nerve density) under conditions of mechanical distension. PMID- 8345586 TI - Positron emission tomography: a new method for determination of renal function. AB - Positron emission tomography (PET) is a newly evolving diagnostic modality that has been widely used in many facets of clinical medicine, but whose use in the diagnosis and management of disorders of the kidney has not been previously described. Employing the radiotracer N-13 ammonia, flow-dependent extraction of this compound after intravenous injection was used to measure renal blood flow (RBF) in a swine model (N = 10). A mean baseline value of 3.16 ml./min./gm. kidney was obtained with this method, in close agreement with values previously reported using established invasive techniques. Four conditions known to affect RBF were also studied to determine the ability of PET to detect changes in RBF. Kidneys were subjected to varying durations of warm ischemia, demonstrating a progressive decrease in RBF with increasing ischemic insult, with return to normal significantly impaired in animals exposed to the greatest degree of ischemia (180 minutes versus 150 or 120 minutes ischemia). Cross-transplant between animals produced acute allograft rejection and a corresponding marked decrease in RBF that failed to normalize. After unilateral nephrectomy, RBF increased two-fold in the remaining kidney by 7 days (R = 0.79), as predicted for compensatory renal hypertrophy. Lastly, there was an inverse, linear relationship between toxic cyclosporine level and RBF (R = 0.68), indicative of vascular mediated cyclosporine nephrotoxicity. Positron emission tomography is safe and efficient, and yields an accurate measurement of RBF in several important physiologic states. The development of PET as a quantitative measure of renal function is promising. PMID- 8345587 TI - Hereditary prostate cancer: epidemiologic and clinical features. PMID- 8345588 TI - Alterations in renal stone risk factors after space flight. AB - Exposure to the microgravity environment of space produces a number of physiological changes of metabolic and environmental origin that could increase the potential for renal stone formation. Metabolic, environmental and physicochemical factors that influence renal stone risk potential were examined in 24-hour urine samples from astronauts 10 days before launch and on landing day to provide an immediate postflight assessment of these factors. In addition, comparisons were made between male and female crewmembers, and between crewmembers on missions of less than 6 days and those on 6 to 10-day missions. Results suggest that immediately after space flight the risk of calcium oxalate and uric acid stone formation is increased as a result of metabolic (hypercalciuria, hypocitraturia, pH) and environmental (lower urine volume) derangements, some of which could reflect residual effects of having been exposed to microgravity. PMID- 8345589 TI - Management of renal cell carcinoma with coexistent renal artery disease. AB - Coexistence of renal cell carcinoma and renal artery disease is an unusual and challenging problem. From 1969 to 1991, 34 patients presented with localized renal cell carcinoma and renal artery disease affecting all of the functioning renal parenchyma. These patients represented 4 categories: 1) a solitary kidney with renal cell carcinoma and renal artery disease (5), 2) bilateral renal cell carcinoma and coexistent renal artery disease (5), 3) unilateral renal cell carcinoma and contralateral renal artery disease (13), and 4) unilateral renal cell carcinoma and bilateral renal artery disease (11). Atherosclerosis was the most common cause of renal artery disease (30), followed by medial fibroplasia (2), renal artery aneurysm (1) and arteriovenous malformation (1). A total of 23 patients (68%) presented with azotemia (serum creatinine 1.5 mg./dl. or more) and 11 (32%) presented with hypertension. All patients underwent complete surgical excision of renal cell carcinoma. A nephron sparing operation was performed preferentially (30 patients) and bilateral renal cancer operations were staged. Eight patients underwent simultaneous partial (6) or radical (2) nephrectomy and surgical renal revascularization. There were no operative deaths. Postoperatively, preservation of renal function was achieved in 33 patients and 1 required chronic dialysis. At mean followup of 47 months 23 patients (68%) were alive with no evidence of malignancy and 2 were alive with recurrent renal cell carcinoma. Three patients died of metastatic renal cell carcinoma, while 6 died of unrelated causes. All of the latter 6 patients were free of renal cell carcinoma at death. Nephron sparing surgery combined occasionally with renal arterial reconstruction can yield gratifying results in this complex patient population. PMID- 8345591 TI - Failed endopyelotomy: implications for future surgery on the ureteropelvic junction. AB - During the last 8 years we performed 212 endopyelotomies with an overall success rate of 86%. To determine if the failed endopyelotomies resulted in a more difficult subsequent open corrective procedure, we compared the procedures and outcomes of 15 failed endopyelotomies with 16 control patients undergoing pyeloplasty who had not undergone a previous endopyelotomy. The variables of duration of the surgical procedure, average estimated blood loss, average number of transfusions and average length of hospitalization were analyzed for both groups. No statistically significant differences were detected for any of these variables. We conclude that despite a previously failed endopyelotomy, a subsequent open operation on the ureteropelvic junction, although slightly more difficult, was not associated with an increased morbidity rate nor less successful than de novo pyeloplasty. Therefore, we continue to advocate endopyelotomy as the procedure of choice for obstruction of the ureteropelvic junction. PMID- 8345590 TI - Treatment of metastatic renal cell carcinoma with recombinant interleukin-2 in combination with vinblastine or lymphokine-activated killer cells. AB - Fifty patients with metastatic renal cell carcinoma were treated with recombinant interleukin-2 alone or in combination with the antitumor drug vinblastine or lymphokine-activated killer cells. Of 34 evaluable patients treated with intravenous bolus interleukin-2, 1 (3%) had a partial response. Vinblastine increased myelotoxicity but did not enhance response to interleukin-2 in 15 of these patients. Two partial responses were observed among 15 patients treated with lymphokine-activated killer cells in addition to interleukin-2. In 1 patient biopsy documented complete resolution of hepatic metastases lasting for 1 year was observed. All responders had undergone previous nephrectomy and none had multiple sites of metastatic disease. Toxicity was significant and caused termination of therapy in 40% of the patients. Biological therapy using interleukin-2 can result in prolonged responses in renal cell cancer but future trials should be directed at lessening toxicity. PMID- 8345592 TI - Extracorporeal shock wave lithotripsy in situ or after push-up for upper ureteral calculi: a prospective randomized trial. AB - A total of 110 patients with upper ureteral calculi was admitted to a prospective trial and randomly allocated to 2 groups: 1 group treated with in situ extracorporeal shock wave lithotripsy (ESWL) and 1 group treated with ureteral manipulation before ESWL. All patients had solitary upper ureteral calculi without urinary infection. The stones had to be smaller than 1 cm. and located more than 2 cm. lateral to the spine. ESWL was performed with the Dornier HM3 lithotriptor. One patient in the in situ ESWL group had to be treated twice because disintegration of the stone was insufficient after the initial treatment session. All other patients underwent only 1 treatment session. Because 16 patients were lost to followup, 94 were evaluable for the analysis of immediate and long-term results. For disintegration of the stones in situ ESWL needed significantly more shock waves (1,844 +/- 639 versus 1,297 +/- 473, p < 0.001) and a higher voltage (19.5 +/- 1.4 versus 18.7 +/- 0.9 kv., p < 0.001). There were no severe complications in either treatment group. At 3 months 44 of 46 patients (96%) after in situ ESWL and 45 of 48 (94%) after ureteral manipulation before ESWL were free of stones. In view of these results it is suggested that uncomplicated upper ureteral calculi (as defined previously) should be treated first with in situ ESWL, thus, avoiding an invasive procedure. PMID- 8345593 TI - The fate of the iatrogenic retroperitoneal stone. AB - Ureteral perforation with resultant retroperitoneal stone expulsion is a recognized complication of ureteroscopy. In a 5-year retrospective review of 400 cases we identified a 1.3% incidence of iatrogenic retroperitoneal stone dislodgment. Average followup was 21 months. Four cases were managed with observation and 1 required surgical correction of a ureteropelvic junction stricture. We discuss the management of this problem, which begins with thorough radiographic documentation in the perioperative period. Aggressive ureteroscopic manipulation and attempted stone retrieval are not warranted, and a ureteral stent should be placed. Radiographic followup and clinical observation confirm the low morbidity associated with retroperitoneal urinary stones. Patient understanding of the extra-ureteral stone location is essential to avoid misdiagnosis and mismanagement by uninformed physicians in the future. PMID- 8345594 TI - Yang needle tunneling technique in creating antireflux and continent mechanisms. AB - A total of 7 patients underwent cystectomy due to bladder malignancy and the ileum was used for lower urinary tract reconstruction (5 underwent bladder substitutions, 1 an internal ileal reservoir and 1 ileal conduit diversion). Antireflux mechanisms were created by submucosally tunneled ureters and in 1 case the continent mechanism was created by a submucosally tunneled ileal tube. In all cases the Yang needle was used, which consists of a needle portion and a forceps portion. The selected position of the ileum for ureteral and ileal tube implantation is injected with normal saline submucosally to form a wheal. The Yang needle is introduced submucosally, guided under the wheal for a certain distance and then directed through the ileal wall. Smooth dilation of the tunnel is achieved with the dilated portion of the needle without laceration of the mucosa. The needle portion is then removed. The ureter or ileal tube is grasped by the forceps portion of the needle and brought through the tunnel to the mucosal side of the ileal plate, followed by mucosa-to-mucosa anastomosis. For all 14 ureteral implantations only 1 ureter had reflux on postoperative radiographic studies and only 1 of 4 hydroureters remained. No additional obstructive lesions or pyelonephritis was noted postoperatively. The patient whose continent mechanism is formed by the submucosal tunneled ileal tube method is continent and free of an appliance. The Yang needle tunneling technique may be a choice in the creation of antireflux and continent mechanisms. PMID- 8345595 TI - Direct (nontunneled) ureterocolonic reimplantation in association with continent reservoirs. AB - A total of 190 patients underwent continent urinary diversion using the Florida pouch. Direct mucosa-to-mucosa ureterocolonic reimplantation was used in 165 patients (326 ureters). Of the first 30 ureters in patients who underwent antireflux tunneled reimplantation obstruction occurred in 4 (13.3%). Obstruction developed directly in 16 of the ureters reimplanted (4.9%), and 3 of the 6 plicated and reimplanted megaureters (50%). Among the obstructed units 3 (13%) were treated unexpectedly by autonephrectomy, while the other 20 units (87%) were treated with percutaneous balloon dilation and internal stenting for 6 to 8 weeks. In the latter group 12 units (60%) recovered function, 3 (15%) had pyelonephritis requiring nephrectomy and 5 (25%) stabilized following a new reimplantation. Reflux was demonstrated in 23 units (7%). All units with reflux are being followed conservatively and renal deterioration has not been demonstrated. The incidence of ureteral obstruction with direct reimplantation is lower compared to a tunneled technique. This reimplantation procedure is technically simpler than others and is safe in adults when performed in association with a large volume, continent colonic reservoir. PMID- 8345596 TI - The valved S-shaped rectosigmoid pouch for continent urinary diversion. AB - Continent urinary diversion to the valved S-shaped rectosigmoid pouch was performed in 9 female and 6 male patients 12 to 65 years old (mean age 51 years). The pouch was constructed by detubularization and S-shaped reconfiguration of 30 cm. of the intact rectum and sigmoid colon. The ureters were reimplanted into the pouch using antireflux techniques. Reflux of urine from the pouch to the proximal colon was prevented by fashioning an intussusception valve. The construction was protected by a transverse colostomy for 6 to 8 weeks. With a followup of 3 to 24 months (mean 11 months), all patients are continent during the day and also at night with evacuation intervals of 3 to 6 hours. There have been no cases of symptomatic urinary tract infection. Only 1 patient had mild hyperchloremic acidosis. No patient complained of abdominal distention or constipation. Contrast study via the anus (radiography of the pouch) showed that the intussusception valve was competent in all but 1 patient in whom reflux to the proximal colon was noted due to sliding of the nipple valve, which was revised successfully. Urodynamic studies (cystometry of the pouch) showed a capacity of 400 to 900 ml. (mean 600) with an intraluminal pressure of 22 cm. water (range 10 to 34) at maximal filling. The valved S-shaped rectosigmoid pouch is a faster and simpler surgical procedure compared with the modified rectal bladder (valved rectum augmented with ileum). It also results in a smooth postoperative course, since an intestinal anastomosis proximal to the colostomy is avoided. PMID- 8345597 TI - Continent urinary reservoirs. PMID- 8345599 TI - Long-term consequences of urethral stents. AB - The results of the self-expandable urethral stent (Wallstent) in the treatment of urethral strictures were evaluated in 7 patients with a followup of 23 to 31 months. The 4 failures were caused by exuberant fibrotic proliferation in the lumen of the stent, which required further endoscopic treatment in 2 patients and even surgical removal of the stent in 1. In the other 2 patients the fibrotic proliferation was progressive and will require further treatment. In 1 patient there is slowly progressive proliferation and a diminishing urine flow rate, and in 2 the fibrotic proliferation seems to be stable. Early reports on the stent suggest that its use will obviate the necessity for complex surgery of urethral stricture. Strictures involving layers deeper than the urothelium and traumatic strictures are not good indications for the self-expandable stent. As this technology continues to evolve, we must continue to follow these patients closely and be attentive to the possible long-term consequences. PMID- 8345598 TI - Neoadjuvant cisplatin, methotrexate and vinblastine for muscle-invasive bladder cancer: long-term followup. AB - A total of 26 patients with locally advanced bladder cancer received chemotherapy consisting of cisplatin, methotrexate and vinblastine. Radical cystectomy was performed in 24 of 26 patients (92%) receiving neoadjuvant therapy, with a pathological complete response in 6 (23%) and pathological partial response in 1 (4%) for an overall response rate of 35% (95% confidence limits 17 to 56%). The overall median survival time is currently undefined. Of the patients 15 (58%) are alive with a median followup of 48.6 months. Response rates from this neoadjuvant chemotherapy appear to be similar to those reported with methotrexate, vinblastine, doxorubicin and cisplatin, and may represent a therapeutically equivalent regimen but neither may be curative in the majority of the patients. PMID- 8345600 TI - Transurethral polytetrafluoroethylene injection in female patients with urinary continence. AB - We present our results with the use of transurethral injection of polytetrafluoroethylene (Teflon) in 128 female patients with moderate to severe urinary incontinence from 1964 to 1991. Of the patients 60% had undergone previous surgical treatment for the incontinence. The etiologies included stress incontinence, neurogenic bladder, congenital anomalies, trauma and others. More than 73% of the patients improved (54.3% were totally dry). The failure rate was 27%. Complications were minimal. Urinary tract infection and temporary urinary retention occurred in 7 and 6 patients, respectively. Mean followup was 31 months. This study demonstrates that transurethral polytetrafluoroethylene injection is a useful treatment of moderate to severe urinary incontinence in female patients. Polytetrafluoroethylene is particularly useful for patients with failed previous incontinence procedures and poor surgical candidates. Failures are more likely in patients with periurethral fibrosis secondary to a previous urethral operation. PMID- 8345601 TI - Intracavernous sodium nitroprusside: inappropriate impotence treatment. AB - On the basis of reports describing nitric oxide as a form of endothelium-derived relaxing factor and on our own experience with intracavernous use of nitric oxide releasing substances in animal models, we undertook an approved human study of intracavernous sodium nitroprusside as a treatment for impotence. We report our early experience in which severe hypotension and only mild tumescence in our first 3 patients caused us to discontinue the trial. PMID- 8345602 TI - Carbon dioxide laser treatment of lichen sclerosus et atrophicus. AB - We followed 62 men treated with the carbon dioxide laser for lichen sclerosus et atrophicus for an average of 30 months (3 months to 7 years). Of the patients 47 (76%) became asymptomatic and 10 (16%) had minor residual symptoms. In 26 patients (40%) concomitant superficial meatal stenosis was simultaneously treated with laser meatotomy. The cosmetic and functional results of treatment were highly encouraging. Provided that radicality is achieved at the primary application, the carbon dioxide laser is an excellent therapeutic modality for lichen sclerosus et atrophicus. PMID- 8345603 TI - Varicocele-related infertility is not associated with increased sperm-bound antibody. AB - Immunological factors have been implicated as a cause of unexplained infertility. Previous studies have demonstrated increased levels of sperm-bound antibody in infertile men with varicoceles and have postulated their role in varicocele related infertility. However, these studies were performed using an enzyme-linked immunosorbent assay. We evaluated retrospectively 111 male patients referred for infertility using a direct immunobead assay. Of the patients 29 had grade II or III varicoceles (that is palpable or easily visualized) and 82 were without varicocele. Four patients who had undergone vasovasostomy were included as controls for the assay. A direct immunobead assay was performed for isotype IgG and IgA sperm-bound antibody using a standard protocol. A computerized semen analysis was also performed. Greater than 20% binding, excluding tail tip activity, was considered significant. Of 29 patients with and 82 without a varicocele significant binding was identified in 5 (17%) and 9 (11%), respectively. Chi-square statistical analysis did not reveal this difference to be significant (p < 0.05). All 4 vasovasostomy patients demonstrated significant binding. We conclude from this study that infertile men with varicoceles do not demonstrate significantly increased levels of sperm-bound antibody compared to infertile controls and, therefore, sperm-bound antibody does not appear to have a significant role in varicocele-related infertility. PMID- 8345604 TI - Chest staging in testis cancer patients: imaging modality selection based upon risk assessment as determined by abdominal computerized tomography scan results. AB - We compared chest computerized tomography (CT) to chest x-ray as chest staging modalities in testis cancer patients on the basis of abdominal CT findings. We identified 92 patients who presented with negative staging abdominal CT scans and 52 with abnormal abdominal CT scans. Of these patients 42 and 32, respectively, underwent a chest x-ray and chest CT concurrently as part of the initial staging evaluation. Dictated x-ray reports were used to compare study findings. Findings on chest x-ray and chest CT were considered concordant if both studies identified similar chest abnormalities. Findings were considered discordant if either study failed to identify an abnormality noted on the other test. Patient outcome during followup, response to therapy or chest pathology was used to discriminate benign from malignant radiological abnormalities. Radiographic chest abnormalities (chest x-ray and/or chest CT) were identified in 12 of the 42 patients with negative abdominal CT scans. Three of these 12 studies represented metastasis with the remainder being benign. Imaging results were concordant in all 3 patients with chest metastasis and 5 of 9 with benign chest disease. Chest x-ray identified abnormalities not observed on chest CT in 1 patient, with chest CT identifying abnormalities not observed on chest x-ray in 3. Radiographic chest abnormalities (chest x-ray and/or chest CT) were identified in 15 of 32 patients who had a positive abdominal CT. All chest lesions identified in these patients were believed to represent metastatic disease. Chest x-ray failed to identify abnormalities present on chest CT in 4 of the 15 patients. The use of chest CT as a staging modality in abdominal CT negative patients failed to increase diagnostic sensitivity relative to chest x-ray alone. However, in 32 patients with abnormal abdominal CT scans the use of chest x-ray alone would have missed intrathoracic metastatic disease in 4. These data suggest that chest x-ray may be the preferred initial chest staging study for testis cancer patients with negative abdominal CT, while chest CT is mandated in patients with abnormal abdominal CT. PMID- 8345605 TI - p53 gene mutations in Chinese human testicular seminoma. AB - Genomic deoxyribonucleic acid from 17 primary human testicular seminomas was screened for the presence of mutations in exons 5 to 8 of gene p53, using the single strand conformation polymorphism assay, followed by direct deoxyribonucleic acid sequencing. The p53 mutations in 1 allele leading to an amino acid change but a normal (wild-type) sequence in the remaining allele were identified in 4 of 17 seminomas (23.5%). Sites of mutations were in exon 5 (codon 141), exon 7 (codon 238, codon 258) and exon 8 (codon 270). The present study suggested that mutation of the p53 gene is involved in the development of human testicular seminoma as in the case of several other types of human cancers. PMID- 8345606 TI - Laparoscopic standard pelvic node dissection for carcinoma of the prostate: is it accurate? AB - The acceptably low morbidity of laparoscopic pelvic lymphadenectomy has allowed us to perform the procedure systematically on all patients who presented with localized adenocarcinoma of the prostate. Data on 147 consecutive cases enable us to state that the overall accuracy and morbidity of this method are equal if not better than the rates available in the literature for open procedures. In addition, analysis shows that the standard dissection is more accurate than the obturator dissection because in 30% of the patients with positive nodes malignant infiltrates were found in the iliac specimen only. Finally, it appears that patients in whom the malignancy was detected by ultrasound only may not require lymphadenectomy because in our group of 28 patients no positive nodes were detected. PMID- 8345607 TI - Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. AB - We evaluated recovery of erections and urinary continence following anatomical radical retropubic prostatectomy in a series of 784 consecutive patients with clinical stage A or B prostate cancer. Nerve sparing radical prostatectomy was performed in men deemed appropriate candidates. Recovery of erections sufficient for intercourse and urinary continence were analyzed controlling for patient age, pathological tumor stage and the performance of unilateral or bilateral nerve sparing surgery in men followed for a minimum of 18 months. Erections were regained in 149 of 236 preoperatively potent men (63%) treated with bilateral and 24 of 59 (41%) treated with unilateral nerve sparing surgery. Recovery of erections correlated with patient age and pathological tumor stage in patients treated with bilateral nerve sparing surgery. Continence was regained in 409 of 435 patients (94%) and did not correlate with patient age, tumor stage or nerve sparing surgery. Anatomical radical retropubic prostatectomy can be performed with favorable results in preserving potency and urinary continence. Better results are achieved in younger men with organ confined cancer. PMID- 8345608 TI - Seminal vesicle parameters at 10-year intervals measured by transrectal ultrasonography. AB - The volume, maximum horizontal area, maximum length, maximum width and depth of the seminal vesicles were measured by transrectal ultrasonography in 76 subjects without seminal vesicle disorders, divided into 7 groups at 10-year intervals. The average of each parameter in each group was presented. The volume and maximum horizontal area began to decrease after the age of 60 years. No statistically significant difference among subject ages was observed for the other 3 parameters. A correlation was observed between the volume and maximum horizontal area of the seminal vesicles. Our study confirmed that maximum horizontal area of the seminal vesicles may be substituted for the volume. PMID- 8345609 TI - Oral immunotherapy of recurrent urinary tract infections: a double-blind placebo controlled multicenter study. AB - We treated 166 patients suffering from recurrent urinary tract infections under double-blind conditions for 3 months with 1 capsule daily of either the immunostimulating bacterial extract (85) or a placebo (81), followed by a 3-month observation period without the test drugs. The bacterial extract exerted a significant beneficial curative action and long-term consolidative effect on the frequency of recurrent urinary tract infections with marked improvements in the characteristic signs and symptoms. It was significantly superior to placebo for the majority of the assessed parameters: number of recurrent urinary tract infections, bacteriuria, leukocyturia, erythrocyturia, nitrituria, albuminuria and casts in urine. Consumption of antibiotics, chemotherapeutics, urinary antiseptics or disinfectants was significantly less under active drug therapy compared to placebo. Tolerance was good with only 2 side effects reported in 2 patients (2%) in the active group compared to 11 among 5 (6%) in the placebo group. Therefore, the bacterial extract can be considered an efficient and well tolerated drug for the treatment of urinary tract infections, and their accompanying signs and symptoms, as well as for decreasing the risk of recurrences and the need for antibiotics and other antibacterial drugs. PMID- 8345611 TI - Penile prosthesis corporotomy closure: a new technique. AB - A new technique for corporotomy closure during penile prosthesis implantation is described. Horizontal mattress sutures placed after the corpus cavernosum is opened serve first as stay sutures and then are used to close the corporotomy after device implantation. This technique eliminates placing stay sutures as a separate step, avoids damage to the prosthesis and provides an aesthetic horizontal mattress closure. PMID- 8345610 TI - A new use of ureteroscopy. AB - Failure to deflate a Foley balloon is a rare but annoying complication. We describe 2 simple techniques to solve this problem. PMID- 8345612 TI - Automatic integrated circuit card system for recording 24-hour uroflowmetry. AB - A new system for obtaining accurate and stable urine flow data was developed, in which patients have a key role in recording their own urinary flow data. Flow curves and urination data are recorded on an integrated circuit card, which the patient carries in a pocket. Before urinating, the patient inserts the card into the system. Urination data are recorded automatically. The card can record up to 14 days worth of urination data. A personal computer then calculates and prints all of the flow curves including maximum flow rate, average flow rate, voided volume, duration time, hesitation time, and date and time of urination. This system is useful for detecting subtle changes in urination patterns. Typical circadian rhythms for urination can also be recorded. With this integrated circuit card system the clinical course under alpha-blocker administration could be precisely monitored. PMID- 8345613 TI - Urinary dysfunction in tropical spastic paraparesis: preliminary urodynamic survey. AB - Tropical spastic paraparesis is an infection caused by human T lymphotropic virus type 1 (HTLV-1). We present the urodynamic findings in 4 female and 1 male patient with tropical spastic paraparesis. All patients underwent synchronous video-pressure-flow urodynamics, while 3 also underwent electromyographic examination. Of the 5 patients 4 presented with detrusor external sphincter dyssynergia and 1 had detrusor hyperreflexia with a coordinated sphincter contraction. The preliminary results of this series suggest that patients with tropical spastic paraparesis and voiding symptoms should undergo urodynamic examination so that diagnosis and appropriate therapy may be instituted. PMID- 8345614 TI - Laparoendoscopic upper pole partial nephrectomy with ureterectomy. AB - A 14-year-old white girl presented with a history of recurrent urinary tract infections beginning at age 18 months. Anatomical evaluation revealed bilateral duplication of the collecting systems. On the right side of the upper pole moiety ended at an obstructing orthotopic ureterocele. On the left side the upper pole moiety was associated with an ectopic ureteral orifice. The patient underwent laparoendoscopic right upper pole partial nephrectomy with ureterectomy. To our knowledge this is the first report of a laparoendoscopic upper pole partial nephrectomy. Details of the procedure are discussed. PMID- 8345615 TI - The changing urodynamic pattern in infants with myelomeningocele. AB - A total of 43 infants with spina bifida was evaluated with a standard simplified urodynamic technique to determine whether bladder behavior altered with development and the optimal timing for urodynamic testing. Using urodynamic evaluation plus renal ultrasound and voiding cystourethrography the patients were divided into 2 groups: 1) those with a favorable prognosis and 2) those with an unfavorable prognosis. Only 55% of the initial urodynamic studies were predictive of future clinical course. The patients who worsened generally did so in the first 6 months of life. Of the patients initially believed to have an unfavorable prognosis 86% improved or stabilized with therapy. Urodynamic testing appears to be an important adjunct at 6-month intervals in infancy and early childhood as bladder behavior continues to evolve. PMID- 8345616 TI - Urological aspects of sacrococcygeal teratoma in children. AB - Sacrococcygeal teratoma is the most common extragonadal germ cell tumor of infancy. Associated urological complications, most of which are reported in children with malignancy, include vesicoureteral reflux, ureteral and urethral obstruction, and neurogenic bladder. To evaluate the influence of tumor grade and type on adverse urological outcome we reviewed the charts of 29 children with sacrococcygeal teratoma and correlated urological problems to lesion type and grade. No correlation was noted between tumor grade and the incidence of urological complications. The most common urological complications were neurogenic bladder in 12% of the patients, ureteral obstruction in 10% and vesicoureteral reflux in 7%. The highest incidence of urological complications (81%) was seen in patients with type IV (presacral) disease. We recommend early radiographic and neurourodynamic evaluation in all children with sacrococcygeal teratoma. PMID- 8345617 TI - Potassium thiophosphate laser treatment of genitourinary hemangioma in the pediatric population. AB - Multiple hemangiomas of the urogenital system are uncommon lesions that usually recur and can cause significant morbidity. Three pediatric patients with urethral, bladder, penile, scrotal and vaginal hemangiomas underwent treatment of these lesions with the potassium thiophosphate laser. All patients had multiple lesions and suffered from recurrent bleeding before treatment. Potassium thiophosphate photocoagulation was delivered to the surface, urethral and vaginal lesions. Treatment-associated bleeding did not occur in any case. Followup urogenital and cystoscopic examinations revealed complete obliteration or marked diminution in the size of the treated hemangiomas. All patients had a decrease in the frequency and intensity of bleeding episodes and 2 were subsequently without further episodes of bleeding. Potassium thiophosphate laser photoablation provides excellent results in the pediatric population and is preferred to more extensive surgical intervention. PMID- 8345618 TI - Hygroma renale: pararenal lymphatic cysts associated with renin-dependent hypertension (Page kidney). Case report on bilateral cysts and successful therapy by marsupialization. AB - A total of 42 cases of large symptomatic parapelvic or pararenal lymphatic cysts has been reported since 1890, of which 54% were associated with hypertension and 14% were bilateral. We report on a patient in whom during a 3-month period abdominal pain and distention developed successively on both sides associated with hypertension. Initially, ultrasound and computerized tomography revealed a large multicystic pararenal lymphatic mass on the right side and small parapelvic hilus lesions on the left side. Two months after resection and marsupialization of the large cyst on the right side the small hilus lesions on the left side developed into large pararenal cysts requiring the same therapeutic measures. Hypertension was reversible after surgery in both instances; at the second operation high preoperative and lower postoperative renin activity, active renin, total renin, aldosterone and atrial natriuretic factor in plasma were noted. Immunoreactive active and total renin levels in the lymph fluid were elevated, a finding that may be explained by the renal origin of the lymph. Marsupialization is a kidney preserving measure that reverses all symptoms of large pararenal cysts, including Page kidney hypertension. PMID- 8345619 TI - Strategies for the successful transplantation of the horseshoe kidney. AB - Horseshoe kidney is probably the most common renal fusion anomaly. Horseshoe kidneys have been successfully transplanted en bloc into a single recipient or, alternatively, they have been divided and implanted into 2 patients. Despite these facts the use of horseshoe kidney allografts for transplantation is rare. We report a case of the successful transplantation of an en bloc horseshoe kidney into a single recipient. The evaluation of fused kidneys for transplantation, technical considerations and previously reported cases are discussed. PMID- 8345620 TI - Obliterative pyeloureteritis: a complication of stone disease in patients with urinary conduit diversion. AB - In 4 patients with cutaneous urinary diversion who underwent percutaneous ureteral stone removal, similar ureteral complications developed as a result of severe ureteritis at the site of the stone. Ureteral narrowing occurred within days of percutaneous ureteral stone removal, progressing to complete occlusion in 2 cases. These complications led to prolonged hospitalization and additional procedures for each patient. One patient with an occluded ureter was lost to followup. Two patients responded satisfactorily to repeated ureteral dilations and prolonged stenting. One patient underwent excision of the affected ureteral segment. The average interval between tube placement and removal of tubes and stents was 15 weeks in 4 patients. The average inpatient period was 24 days. Patients with a cutaneous urinary conduit diversion may be at increased risk for complications following percutaneous treatment of ureteral stones. This risk may be secondary to an intense inflammatory response due to infection and other local factors. PMID- 8345621 TI - Percutaneous nephrostomy drainage in the treatment of severe hemorrhagic cystitis. AB - We report on 2 patients who underwent urinary diversion with bilateral percutaneous nephrostomy tube drainage for intractable hemorrhagic cystitis. Both patients received cyclophosphamide-based chemotherapy and 1 also underwent pelvic irradiation for locally advanced prostate adenocarcinoma. In each case the bleeding gradually ceased during a 1-week period. Both patients were alive at 6 months and were voiding spontaneously. We propose that the mechanism of treatment involves diverting endogenous urokinase as well as avoiding overdistention of the bladder. PMID- 8345622 TI - High flow priapism: a spectrum of disease. AB - We describe 4 cases of high flow arterial priapism, ranging from 1 week to 3 years in duration. The mode of presentation, evaluation using a duplex scanner, treatment and ultimate resolution are discussed. In 1 patient treated with ice compression the erection subsided spontaneously. One patient underwent percutaneous embolization and achieved detumescence. In 2 men a vascular pseudocapsule formed around the site of the ruptured cavernous artery that provided an important anatomical landmark for intraoperative localization. The ruptured branch of the cavernous artery was ligated in an open procedure. Based on these cases and a review of the literature, we outline a modified diagnostic and therapeutic approach for patients with high flow arterial priapism. PMID- 8345624 TI - Carcinoma of the rete testis: case report and review of the literature. AB - The literature suggests that carcinoma of the rete testis is a rare neoplasm of unknown etiology that arises in the mediastinum testis and may grow slowly for months before clinical detection. Diagnosis is often confounded by symptoms suggesting inflammation in middle aged and older men presenting with diffuse enlargement rather than discrete testicular nodules. Pathological features are those of an adenocarcinoma but are not sufficiently distinctive to identify the rete testis as the site of origin. Many patients die of the disease soon after diagnosis despite local resection with or without adjuvant therapy. Long-term survival has been observed in at least 2 cases and more than 40% of the patients were alive without disease when reported in the literature. Much of the available information is incomplete, however, and firm conclusions regarding the nature of this cancer must await more solid data. PMID- 8345623 TI - Color Doppler ultrasound for the diagnosis of segmental testicular infarction. AB - We report a case of segmental infarction of the testis associated with scrotal pain diagnosed by color Doppler ultrasound. Histological examination of the testis confirmed the diagnosis. Use of this imaging modality may obviate surgical exploration in select cases. PMID- 8345625 TI - The syndrome of inappropriate antidiuretic hormone secretion in a patient with adenocarcinoma of the prostate. AB - We report the syndrome of inappropriate antidiuretic hormone secretion in a 59 year-old man with stage C adenocarcinoma of the prostate. Serum antidiuretic hormone levels returned to normal following treatment with a gonadotropin releasing hormone analogue. To our knowledge this case represents the first in which resolution of this syndrome occurred with treatment of the carcinoma. PMID- 8345626 TI - The resource-based relative value scale: methods, results and impacts on urology. AB - Increased concern for rising health care costs in the United States has led to the passage of legislation to reform physician payment for Medicare services based on resource inputs. In January 1992 the Health Care Financing Administration began implementing the new law, which replaces the existing Medicare system of physician payment with a fee schedule based on the resource based relative value scale (RBRVS). We summarize the methods and data used to derive the RBRVS for urology. A national random sample of 115 practicing urologists completed structured telephone surveys to provide ratings of physician time and work required before, during and after most frequently performed urological services. Subsequent survey cycles with urologists provided further refinement. Urologists then participated in a cross-specialty physician panel to link services from all specialties onto a common scale. This common scale was adjusted for geographic differences in practice overhead costs and malpractice insurance premiums. A monetary conversion factor, determined by the Health Care Financing Administration, was then applied to convert the RBRVS into a Medicare fee schedule. The merits and demerits of the scientific process used to develop and maintain the relative value scale are extensive. While statistically valid and reproducible, the study results have been altered in the political arena. The results and impacts of the new Medicare payment system on urology will be significant, although it is not yet clear how urological practice will be affected. Although faring better than most surgical specialties, urologists stand to lose approximately 8% of their Medicare income when the new fee schedule is fully implemented. There will be relative gains for evaluation and management services and losses for most invasive procedures. PMID- 8345627 TI - Re: Risk factors for male partner antisperm antibodies. PMID- 8345628 TI - Immunohistochemical localization of epidermal growth factor and transforming growth factor alpha in the male rat accessory sex organs. AB - We examined the presence of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) in the prostate (ventral, lateral, dorsal lobes), coagulating gland and seminal vesicle of Fisher 344 adult male rats by immunohistochemical and radioimmunoassay methods. Immunohistochemically demonstrable EGF was localized in the luminal secretion only of the dorsal lobe of the prostate. Reactive TGF alpha was localized in the lateral lobe (100% of epithelial cells), dorsal lobe (about 40% of the epithelial cells) and seminal vesicle (100% of epithelial cells), but not in the coagulating gland or ventral lobe of the prostate. Radioimmunoassay also demonstrated a measurable amount of TGF alpha in the lateral lobe (194 pg./gm. wet weight) and seminal vesicle (74 pg./gm.). Assayable EGF was demonstrated at much higher levels in all prostate lobes (ranging from 1.2 micrograms./gm. wet weight in the ventral lobe to 26.4 micrograms./gm. in the dorsal lobe) and wet weight in the ventral lobe to 26.4 micrograms./gm. in the dorsal lobe) and the seminal vesicle (0.9 micrograms./gm.). This is the first report describing the presence of immunoreactive TGF alpha and EGF in the male accessory sex organs. PMID- 8345629 TI - Conditioned media from a renal cell carcinoma cell line demonstrates the presence of basic fibroblast growth factor. AB - In a previous report, we demonstrated the isolation and purification of a heparin binding growth factor from human renal carcinoma, and suggested that this growth factor may play a role in the neovascularity and growth of the tumor. In this report, we demonstrate that the growth of the renal cell carcinoma cell line RC29 is stimulated by the addition of exogenous fibroblast growth factor (FGF), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha). Also, media conditioned by this cell line was able to stimulate growth of the A431 vulvar tumor cell line, known for its high concentration of EGF receptors, 3T3 fibroblasts, human umbilical vein (HUV) cells and RC29 cells. Using heparin sepharose chromatography and then SDS polyacrylamide gel electrophoresis (PAGE), we were able to demonstrate several proteins in the conditioned media of the RC29 cell line. Using Western blot analysis, we detected that at least one of the proteins expressed in this conditioned media was FGF and that it belongs to the basic, not acidic, family of fibroblast growth factors. These findings suggest that renal tumors may express growth factors that may play a direct role in maintaining their unrestricted proliferation. PMID- 8345630 TI - A piece of my mind. Dispatch from the front. PMID- 8345631 TI - 'Female athlete triad' risk for women. PMID- 8345633 TI - Iffy climate deters medical technology innovation. PMID- 8345632 TI - 'Global package' saves money but stirs criticism. PMID- 8345634 TI - From the Institute of Medicine. PMID- 8345635 TI - From the Centers for Disease Control and Prevention. Update: acquired immunodeficiency syndrome--United States, 1992. PMID- 8345636 TI - From the Centers for Disease Control and Prevention. Update: barrier protection against HIV infection and other sexually transmitted diseases. PMID- 8345637 TI - From the Centers for Disease Control and Prevention. Update: hantavirus disease- southwestern United States, 1993. PMID- 8345638 TI - Blood cholesterol measurement in young adults. PMID- 8345639 TI - Blood cholesterol measurement in young adults. PMID- 8345640 TI - Blood cholesterol measurement in young adults. PMID- 8345641 TI - Adolescent tobacco use and physical activity. PMID- 8345642 TI - Definitions for sepsis and organ failure. PMID- 8345643 TI - Primary care in the future. PMID- 8345644 TI - Risk of tuberculosis and time spent in jail. PMID- 8345645 TI - Children who witness violence. PMID- 8345646 TI - Children who witness violence. PMID- 8345647 TI - Risk factors for HIV infection among young adult men in northern Thailand. AB - OBJECTIVE: To determine the sociodemographic and behavioral risk factors associated with human immunodeficiency virus (HIV) infection in two cohorts of young men selected for military service in northern Thailand. DESIGN: Military conscripts were studied cross-sectionally after conscription in May 1991 and November 1991. Risk factors were assessed by interview with trained nonmilitary interviewers. SETTING: Two military training bases in Chiang Mai, Thailand. PARTICIPANTS: A total of 2417 young men aged 19 to 23 years (mean age, 21 years) conscripted by lottery into military service in the Royal Thai Army or Royal Thai Air Force from six provinces in northern Thailand. MAIN OUTCOME MEASURES: Human immunodeficiency virus seroprevalence by enzyme-linked immunosorbent assay confirmed by Western blot and univariate and multivariate analyses of sociodemographic and behavioral risk factors associated with HIV seroprevalence. RESULTS: Overall, 289 (12.0%) of 2417 men were HIV-seropositive at baseline. The strongest associations with being HIV positive were heterosexual activities. History of sex with a female commercial sex worker (CSW) was frequent (96.5% of men who were HIV-positive and 79.0% of men who were HIV-negative) and strongly associated with HIV infection on univariate and multivariate analyses (adjusted odds ratio, 1.60 to 2.07, depending on the frequency of CSW contact). Also, sexually transmitted diseases were common and associated with HIV infection in both univariate and multivariate analyses (adjusted odds ratio, 3.36). Sex with other males and injection drug use were uncommon and not associated with HIV infection. Condom use was reported in 61.5% of men at last sex with a CSW but was not shown to be protective of prevalent HIV infection. CONCLUSION: The epidemic of HIV infection has spread widely among young men in northern Thailand, despite reported frequent and recent use of condoms during sex with female CSWs. Control of HIV infection in this population will probably require more regular and effective use of condoms, prevention and treatment of sexually transmitted diseases, and reduction in the frequency of CSW contact. PMID- 8345648 TI - Very low-calorie diets. National Task Force on the Prevention and Treatment of Obesity, National Institutes of Health. AB - OBJECTIVE: To provide an overview of the published scientific information on the safety and efficacy of very low-calorie diets (VLCDs) and to provide rational recommendations for their use. DATA SOURCES AND EXTRACTION: Original reports obtained through a MEDLINE search for 1966 through 1992 on VLCDs or reducing diets plus obesity, supplemented by a manual search of bibliographies and the opinions of experts in the field of nutrition and weight loss therapy for obesity. Only studies of humans were cited. DATA SYNTHESIS: Current VLCDs are usually provided in the context of comprehensive treatment programs, during which usual food intake is completely replaced by specific foods or liquid formulas containing 3350 kJ/d (800 kcal/d) or less. Weight loss on VLCDs averages 1.5 to 2.5 kg/wk; total loss after 12 to 16 weeks averages 20 kg. These results are superior to standard low-calorie diets of 5020 kJ/d (1200 kcal/d), which lead to weight losses of 0.4 to 0.5 kg/wk and an average total loss of only 6 to 8 kg. There is little evidence that intakes of less than 3350 kJ/d (800 kcal/d) result in better weight losses than 3350 kJ. Intake of at least 1 g/kg of ideal body weight per day of protein of high biologic value appears to be important in helping to preserve lean body mass. Serious complications of modern VLCDs are unusual, cholelithiasis being most common. CONCLUSIONS: Current VLCDs are generally safe when used under proper medical supervision in moderately and severely obese patients (body mass index [weight in kilograms divided by height in meters squared] > 30) and are usually effective in promoting significant short term weight loss, with concomitant improvement in obesity-related conditions. Long-term maintenance of weight lost with VLCDs is not very satisfactory and is no better than with other forms of obesity treatment. Incorporation of behavioral therapy and physical activity in VLCD treatment programs seems to improve maintenance. PMID- 8345649 TI - Pathogenesis of disseminated intravascular coagulation in sepsis. AB - OBJECTIVE: To review new insights in the pathogenetic mechanisms involved in the development of disseminated intravascular coagulation (DIC) in septic patients, in order to develop new directions for therapeutic intervention. DATA SOURCES: Articles and published peer-reviewed abstracts on the mechanism of the initiation of DIC in sepsis. STUDY SELECTION: Studies selected for detailed review were those reporting specifics about the mechanism of activation of coagulation and fibrinolysis in experimental human and animal models of sepsis. Data extraction guidelines for assessing data quality included validity of the model, quality of the laboratory assessment of activation of coagulation and fibrinolysis, and methodological considerations, such as the presence of control experiments and statistical analysis. DATA SYNTHESIS: After the presence of endotoxin in the circulation, significant coagulation activation can be detected. This activation is preceded by an increase in the serum levels of various cytokines, such as tumor necrosis factor and interleukins. Inhibition of the increase in tumor necrosis factor results in inhibition of coagulation activation. Measurement of molecular markers for the activation of coagulation proteins at various levels indicates that the activation of coagulation is mediated by the tissue factor dependent pathway, which is further confirmed by experiments in which the inhibition of the tissue factor-dependent pathway resulted in complete inhibition of coagulation activation. The activation of coagulation seems to be amplified by impaired function of the protein C-protein S inhibitory pathway. An imbalance between coagulation and fibrinolysis, ultimately leading to plasminogen activator inhibitor type 1-mediated inhibition of fibrinolysis, may further promote the procoagulant state. CONCLUSION: The increased knowledge of the various pathogenetic mechanisms of coagulation activation and fibrinolysis in sepsis may have therapeutic implications; however, their efficacy needs to be assessed in appropriate clinical trials. PMID- 8345650 TI - Maintaining hospital quality. The need for international cooperation. PMID- 8345651 TI - CEA monitoring after surgery for colorectal cancer. When is the evidence sufficient? PMID- 8345652 TI - Desocializing health care in a developing country. PMID- 8345653 TI - [Symposium "infections, recently worth noticing". Introductory address]. AB - There was once an idea that the extensive development of antibiotics and vaccines would cause most bacterial and viral infections to fade away someday. However, the occurrence of antibiotic resistant bacteria and variant viruses proved this to be illusion. The spread of HIV infection, since there is no way to cure it so far, is of great concern. The occurrence of methicillin resistant Staphylococcus aureus (MRSA) presents another difficulty in preventing nosocomial infections due to the existence of healthy carriers. The out-break of MRSA in wards is one of the most serious problems in hospital management. HCV is capable of inducing chronic hepatitis, hepatic cirrhosis and hepatoma. HCV is thus a more serious concern today than HBV, since preventive measures against HBV by vaccination and anti-HBV immunoglobulin are fully established. We, doctors, nurses and clinical technologists are apt to be exposed to these hazardous microorganisms and thus should take appropriate precautions during routine work. The present symposium was planned to present recent research on these microorganisms, HIV, MRSA and HCV, so that we can improve our measures to prevent them. PMID- 8345654 TI - [Hepatitis C]. AB - Hepatitis C virus (HCV) is a major cause of post transfusion non-A, non-B hepatitis. The virus contains a positive-strand RNA genome comprised of approximately 9,400 nucleotides. HCV E2/NS1 is probably an envelope glycoprotein (E2). The E2 hypervariable domain appears to contain isolate-specific antibody binding linear epitopes. Recently, comparative sequence analysis of all the complete and partial HCV sequences published to date indicates that known genotypes of HCV can be classified into six basic groups. We report here that the prevalence of HCV-I, HCV-II, and a mixed form are 77.2%, 11.4%, and 11.4%, respectively. Patients with anti-HCV and HCV-RNA positive chronic active hepatitis received 6MU of interferon-alpha or beta everyday for two weeks followed by 6MU thrice a week for 14 weeks. Complete response to interferon treatment was defined as an ALT level normalized within six months after the end of treatment and maintained within the normal limit for an additional six months. Complete response was found in 42.9% of patients treated for 16 weeks. In a six month follow-up of the complete responders, clearance of viremia was observed in 90.3% at the end of interferon treatment and in 71.0% six months after the end of interferon treatment. PMID- 8345655 TI - [Assay of erythropoietin in serum with short term enzyme linked immunosorbent assay method--the clinical significance, Part 1: Relation to anemia in renal failure and hematological disorders]. AB - With a newly developed enzyme linked immunosorbent assay kit TOYOBO Co. in which 2 anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from normal adults, 168 patients with renal failure and 333 patients with hematological disorders. In the patients with renal failure, serum EPO level was normal (52.9%) or reduced (42.9%), and there was no correlation to their hematocrits. However, there was an increment in EPO concentration correlated to their severity of anemia in the most patients with hematological disorders, such as iron deficiency anemia (correlation coefficient r = -0.74), aplastic anemia (r = -0.89), leukemia (r = -0.81), and MDS (r = -0.65). On the other hand, EPO concentration in sera from all the untreated patients with polycythemia vera were significantly low level. But the concentrations of EPO from the patients successfully treated, with normal hematocrit were recovered to normal level. In the patients with secondary polycythemia, there were much varieties in EPO level. Assay of EPO in blood is important not only for diagnosis of polycythemia but also for the analysis of anemia and clinical use of EPO in vivo. The method described here is accurate and technically not complicated, and could be widely induced in most laboratories. PMID- 8345657 TI - [Risk factors of cerebral embolism in patients with atrial fibrillation]. AB - Cerebral embolism is one of the major complications of atrial fibrillation (Af). We studied patients with Af, retrospectively, as to the factors related to cerebral embolism. We examined 82 cases with transthoracic echocardiography (TTE) and trans-esophageal echocardiography (TEE) as well as ambulatory (Holter) ECG and 12 leads ECG. Thirty-three patients had cerebral ischemic attack (CIA), including 14 patients with mitral stenosis (MS) and 19 patients with other heart disease or lone Af (NonMS). The CIA group of NonMS were older than other groups. Both the CIA and NonCIA groups had the same frequency of paroxysmal and chronic Af. In the CIA group, there was a tendency of small amplitude of f wave and longer RR interval than the NonCIA group with ambulatory ECG. The CIA group also had larger left atrial cavity size and aortic diameter with TTE. TEE revealed thrombus formation in 29 cases, and the CIA group had a higher occurrence rate of thrombus than NonCIA group. TEE also detected a fuzzy echo in the left atrium in 88% of the CIA group and 42% of the NonCIA group. The risk factors of cerebral embolism could not be made clear in this study, but a fuzzy echo and thrombus in the left atrium with TEE are specific findings of cerebral embolism. Therefore, older patients with paroxysmal Af, large LAD, AOD, small f wave or long RR interval need to be examined by TEE to detect LA thrombus or a fuzzy echo, which are probably major risk factors of cerebral embolism. PMID- 8345656 TI - [Within-day and day-to-day variations of serum M-CSF levels in healthy volunteers]. AB - We have investigated on within-day and day-to-day variations of serum M-CSF levels in healthy volunteers (ranges of age: 20-21 years old). M-CSF levels in serum were measured using enzyme-linked immunosorbent assay (ELISA). Serum M-CSF levels in early morning were 1.31 +/- 0.30 ng/ml (mean +/- SD, n = 10) in male volunteers, 1.50 +/- 0.13 ng/ml (n = 10) in female volunteers. No significant difference was observed between male and female volunteers in serum M-CSF levels. No significant within-day variations in serum M-CSF levels were also observed. Serum M-CSF levels in period of thirteen days in each individual person were almost constant (n = 5). The inverse correlation was observed between M-CSF levels and number of neutrophils. The correlation, however, was not observed between M-CSF levels and number of monocytes. The present results suggest that there are mechanisms in vivo which maintain serum M-CSF in a constant level in each individual person. PMID- 8345658 TI - [Screening of sleep apnea syndrome using daytime polysomnography--its usefulness and the characteristics of daytime sleep in the patients with sleep apnea syndrome]. AB - Some attempts have been made to screen sleep apnea syndrome (SAS). In this study, we performed daytime polysomnography (DPSG) as a means of screening SAS. 33 patients (28 males and 5 females, a mean age of 50.7 years) who were seen with the complaints of sleep-wake disorders, snoring and breathing disturbance in their nocturnal sleep were subjects for the screening. EEG, EMG, and EOG according to standard polysomnographic technique were recorded from 3:30 (p.m.) for 60 minutes, as additional indicators, oro-nasal airflow and abdominal movement were monitored simultaneously to confirm cessation of breathing. After the screening, we performed conventional polysomnography (PSG) to make a diagnosis of SAS, and compared the diagnosis with the appearance of apnea in the screening. We studied on the characteristics of daytime sleep in SAS and NonSAS by the comparison of EEG variables obtained from DPSG. Sleep apnea was detected in 20 cases with DPSG, 18 cases of these 20 were diagnosed as SAS. However, there were 6 patients who were diagnosed as SAS without the appearance of apnea in the screening. Dominant type of apnea in the screening were corresponded to ones confirmed with PSG, 16 cases showed obstructive type and 4 cases indicated central type. Some statistical differences of EEG variables between SAS and NonSAS were recognized. Number of stage shifts and percentage of stage W to total sleep time were significantly increased in SAS, on the contrary, percentage of stage 2 to total sleep time tended to be lower in SAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345659 TI - [Age-associated morphological change in interventricular septum]. AB - To investigate the morphological features of the interventricular septum (IVS) in the senile heart, we examined 123 normotensives (59 males and 64 females), ranging in age from 22 to 91 yrs using 2D echocardiography. End-diastolic IVS thickness was measured at the mid-portion (M) and at the thickest portion within 15 mm distal to the aorto-septal junction (basal portion, B) on left parasternal long-axis tomogram. The sigmoid shape of the basal portion was evaluated in terms of aorto-septal (AS) angle. M showed no correlation with age, whereas B increased significantly with age in both sexes (males, r = 0.42, p < 0.01; females, r = 0.51, p < 0.01). B/M ratio, therefore, also increased with age (males, r = 0.49, p < 0.01; females, r = 0.39, p < 0.01). The AS angle decreased with age in both sexes (males, r = -0.33, p < 0.01; females, r = -0.51, p < 0.01). There was a significant inverse correlation between B/M ratio and AS angle (males, r = -0.31, p < 0.05; females, r = -0.50, p < 0.01). We conclude that the B/M ratio is a novel index reflecting heterogenously distributed hypertrophy in the IVS associated with age. PMID- 8345660 TI - [Granule-accumulation in VERO cells used for determination of antitoxin titration by micro cell culture method: I. Influence of mouse serum]. AB - When the titration of diphtheria antitoxin of mouse serum was carried out by micro cell culture method using VERO cells, a large number of granules were observed in the cells. In order to examine the influence of this phenomenon on the titration of antitoxin, kinetics of the granule-accumulation was investigated. The granule-accumulation occurred in the cells in the culture medium to which either immunized or normal mouse serum was added. The granule rich cells appeared at the dilution of the serum less than 1:32 and increased in number with the concentration of the serum. After 4 days of incubation 88% of the cells showed granule-accumulation when undiluted serum was added. Besides the mouse serum, those from guinea-pigs, horses, fetal calves and humans were examined. However, intensive accumulation of granules such as shown with mouse serum was not observed. From these results it was suggested that mouse serum might have some unknown mechanism which caused the remarkable accumulation of granules in VERO cells. The nature of granule and influence of this phenomenon on the titration of diphtheria antitoxin will be presented in an accompanying paper. PMID- 8345661 TI - [Effect of surface antigens on granulocytes in phagocytosis]. AB - To analyze phagocytosis mechanism of granulocyte using fluorescent microspheres, changes of phagocytic index, complement receptors, Fc receptors and adhesion molecules on cell membrane, after exogenous stimulation were determined by flow cytometry. The changes of phagocytic index by blocking test was also determined using monoclonal antibodies for receptors. The phagocytic index was decreased by supernatant of S. aureus, and was increased by supernatant of E. coli and phorbol myristate acetate (PMA). By PMA stimulation, surface marker positive cells increased in CR1, IgGFcR2 and decreased in IgGFcR3, LFA-3, Homing receptor, whereas they increased in CR1, IgMFcR, LFA-1 beta and decreased in LFA-3 by the supernatants of S. aureus and E. coli. Blocking test using monoclonal antibodies to individual receptors showed decrease of phagocytic index in CR1, CR3, LFA-1 beta. In this phagocytosis using fluorescent microspheres, the complement receptors were most dedicating in phagocytosis of granulocyte. PMID- 8345662 TI - [Causes of anomalous patterns of haptoglobin using polyacrylamide gel electrophoresis]. AB - We could observe several anomalous electrophoretic patterns of haptoglobin during serotype analysis. We classified these anomalous patterns of haptoglobin into two major classes. The first is the change of number of haptoglobin bands, and the second is the shift from the normal serotype patterns. The change of number of haptoglobin bands was caused by unsaturation of haptoglobin in binding with hemoglobin, mixing of different serotypes by blood transfusion or injection of haptoglobin and serotype variants of haptoglobin. The shift of haptoglobin PAGE pattern was occurred from a large amount of M-protein or lipoproteins in serum. PMID- 8345663 TI - [Isospora belli infection in a patient with adult T cell leukemia]. AB - A 53-year-old man was hospitalized for the development of watery diarrhea associated with decreased appetite and progressive weight loss and was found to have leukocytosis. The white blood cell count was 14,600/microliters with 66 percent abnormal lymphocytes. Serum anti-HTLV-I was positive and monoclonal insertion of HTLV-I provirus into the atypical cell genome was confirmed with the southern blotting hybridization technique. A diagnosis of ATL was made. Examination of fresh stool specimens revealed Isospora belli (I. belli) oocysts. Initial treatment for I. belli consisted of oral trimethoprim 160mg and sulfamethoxazole 400mg given twice daily for nine days. Diarrhea ceased within 2 days of the start of treatment, but I. belli oocysts were again detected after 20 days. Trimethoprim 160mg and sulfamethoxazole 400mg were reinstituted four times daily for 10 days, and then twice daily for 21 days. The clinical response was again dramatic, with rapid clearance of oocysts from the stool. There has been no recurrence of diarrhea. The patient's leukemia was refractory to chemotherapy; the white blood cell count continued to rise, pneumonia developed, and the patient died. I. belli is a previously unrecognized opportunistic pathogen that must be considered in the clinical setting of chronic diarrhea in patients with ATL. PMID- 8345664 TI - [Elevation of serum apo E-rich HDL concentration in a patient with cholestatic liver disease]. AB - A remarkable elevation of serum HDL cholesterol concentration (165mg/dl) was found in a 42-year-old Japanese male with chronic pancreatitis who had been cholestatic for several years. An abnormal slow alpha-migrating lipoprotein, larger in particle size and more enriched with cholesteryl ester and apo E than normal HDL, was found in the patient's plasma. Quantitative determination of apo E-rich HDL revealed a striking increase of this lipoprotein in plasma. After choledocho-jejunostomy, a prompt and remarkable decrease of plasma apo E-rich HDL was observed, indicating a direct contribution of cholestasis to the accumulation of apo E-rich HDL in plasma in this patient. PMID- 8345666 TI - [A study on medical examination items added to periodic health examination as a result of amendment of the Ordinance on Occupational Safety and Health]. AB - In accordance with the recent amendment of the Ordinance on Occupational Safety and Health, anemia (Hb, RBC), liver function (GOT, GPT, gamma-GTP), serum lipid levels (T-Chol, TG) and ECG have become essential items of the general periodic health examination. Data on these items were examined on 86 employees on whom chest radiography, blood pressure, urinalysis and past history revealed no abnormalities in periodic health examination at their companies. The subjects were 58 males and 28 females, between 34 and 66 years old (47.6 years on average). Anemia was found in 3 (3.5%), liver dysfunction in 13 (15.1%), abnormal serum lipid levels in 24 (27.9%) and ECG abnormalities in 8 (9.3%). The new periodic health examination system is thus thought to be useful in the early detection and prevention of adult diseases. To enhance this utility, it appears important to instruct those found abnormal in any parameter to have extensive examination. In discussing liver function and serum lipid level abnormalities, obesity, drinking and food intake should be considered. PMID- 8345665 TI - [Studies on the gamma delta T lymphocytes in the peripheral blood in healthy adults]. AB - Since gamma delta T lymphocytes has been found to be increased in patients with some immunological disorders, there exists clinical needs to determine the population of the cells in peripheral blood in normal subjects. We counted the number of gamma delta T lymphocytes in samples obtained from 151 healthy volunteers, aged from 20 to 69 years, by using a dual-color flow cytometry with fluorescence-conjugated CD3 and anti-TCR-gamma delta antibodies. Distribution ratio of gamma delta T lymphocytes among peripheral blood lymphocytes was 3.8 +/- 2.5% (range, 0.6-16.1%). Difference in the ratio and the number of gamma delta T lymphocytes among sex was not significant, but those decreased slightly but significantly with age. PMID- 8345667 TI - [Surgery under peritoneoscopy--impact on gastroenterology]. PMID- 8345668 TI - [Mutagenicity of the gastric juice in chronic gastritis]. AB - Mutagenicity of the gastric juice in patients with chronic gastritis was determined by reverse mutation test using Salmonella typhimurium TA100 and investigated the relationship between intestinal metaplasia which has been regarded as a precancerous lesion (candidate) of gastric cancer, and atrophy of gastric mucosa. The degree of intestinal metaplasia was quantified in six biopsy specimen for one patient and represented as metaplasia index (MI). The Ames ratio, mutagenicity, of gastric juice showed no significant relationship with the age of patient. On the other hand, Ames ratio and MI, and the age of patient showed significant relationship, respectively (p < 0.01). Furthermore, patients with more intensive atrophy tended to show higher Ames ratio. As shown above, mutagenicity of the gastric juice suggested some relationships to the development of intestinal metaplasia and atrophy of gastric mucosa. PMID- 8345669 TI - [Type IV collagenase activities in human colorectal cancers and its role in cancer invasion and metastasis]. AB - In 36 patients with colorectal cancers, type IV collagenase activities were measured in cancer and non-cancer tissues for evaluating its role in the process of cancer invasion and metastasis. The colorectal cancer tissues revealed remarkably higher activities than the distant normal and tumor-neighboring mucosa (p < 0.001). The activities in the colorectal cancer tissues with high-grade histological venous invasion were higher than those with low-grade histological venous invasion (p < 0.005). But no differences of the activities were found between patients with and without hepatic metastasis. These results suggest that the type IV collagenase plays an important role in the cancer invasion to the blood vessels around the primary site in colorectal cancers. PMID- 8345670 TI - [Evaluation of activated T cells among isolated colonic mucosal lymphocytes in ulcerative colitis--using three color flow cytometry]. AB - In present study, the subsets of activated (HLA-DR+) lamina propria T cells were evaluated in ulcerative colitis (UC) mucosa using three-color flow cytometry. Activated suppressor-inducer T cells (T(si)), helper T cells (Th) and cytotoxic T cells (Tc) were increased in affected mucosa of UC patients not given steroid hormones (SH) compared with in the normal control mucosa. It was supposed that the increase of activated T(si) was the secondary change of inflammation, because this change was demonstrated in non-IBD colitis too. However, the increase of activated Th and Tc might indicate the immunological abnormalities related to the pathogenesis of UC, because these changes were demonstrated only in UC, not in non-IBD colitis. On the other hand, no increase of these activated T cells were demonstrated in affected mucosa of UC patients given SH, perhaps reflecting the immuno-suppressive effect of SH. PMID- 8345671 TI - [Examination of cholangiogram of obstructive jaundice using MRI--compared with PTC and ERCP]. AB - PTC and ERCP are most often used in diagnosis of obstructive jaundice. We studied the possibility of clinical diagnosis using MRI in 33 cases of obstructive jaundice. A clinical diagnosis of malignant tumors could be given in 17 cases out of 20 (85%) using MRI if respiratory standstill was possible. An MRI cholangiogram was particularly effective in describing tearful parting bile ducts and was clearer than PTC in describing negative gallbladders. Choledochal stones could be diagnosed in 58% of cases, which was less than the rate for malignant tumors. MRI is not an invasive examination, can be used in diagnosis of obstructive jaundice, and helps in selecting treatment methods such as PTCD and ERBD. PMID- 8345672 TI - [A case of post transfusion graft versus host disease in hemorrhagic gastric ulcer]. PMID- 8345674 TI - [A case of Crohn's disease manifesting collagen disease-like symptoms as an initial sign]. PMID- 8345673 TI - [A case of extra-gastric, pedunculated leiomyoma of the stomach]. PMID- 8345675 TI - [A case report of ileocecal malignant lymphoma presenting intussusception detected by ultrasonography]. PMID- 8345676 TI - [A case of gas-containing liver abscess complicated with endotoxin shock and DIC]. PMID- 8345677 TI - [Pancreatico-duodenal artery aneurysm associated with complete occlusion of the celiac axis and its rupture]. PMID- 8345678 TI - [A case of pancreatic pseudocyst being complicated with fistulization into the transverse colon and presenting repeated melena]. PMID- 8345679 TI - [Retroperitoneal fibrosis complicated with ascending colon obstruction, report of a case]. PMID- 8345680 TI - [HLA-DR2 DNA typing in Japanese ulcerative colitis]. PMID- 8345681 TI - Sex differences in respiratory and cardiovascular effects of beta-endorphin. AB - An attempt was made to determine sex differences in the effects of beta-endorphin (beta-EP) on respiratory and cardiovascular systems using Wistar rats. By the intracerebroventricular administration of beta-EP (0.18 mg/kg) to normal male and female rats, respiratory rate (RR), heart rate (HR) and mean arterial blood pressure (MABP) were depressed significantly (p < 0.01 or 0.001) and CO2 in expired gas increased significantly (p < 0.01). These suppressive effects of the peptide were transiently blocked by the intravenous injection of naloxone (0.2 mg/kg). No differences in the effects of beta-EP between estrous and diestrous female rats could be detected. The effects of the peptide were significantly stronger in RR, HR and MABP for females than for males (0.001 < p < 0.05). Testectomized rats showed suppressive effects of the peptide to the same extent as intact females, but the effects in ovariectomized rats did not differ from those for intact females. In testectomized and ovariectomized rats treated with testosterone, the former showed the same results as intact males, but not the latter. The suppressive effects of beta-EP on the respiratory and cardiovascular systems are thus remarkably relieved by androgen in male rats. PMID- 8345682 TI - Immunohistochemical localization of paraquat in skin and eye of rat. AB - Immunohistochemical techniques were used to observe the localization of paraquat in the skin and eyes of rats. Paraquat poisoned rats were killed 3 h, 12 h, 24 h, 3 days, 7 days and 10 days after intravenous administration of paraquat. In skin, paraquat was localized in the ducts of sweat glands and sebaceous glands between 3 and 10 days after paraquat injection. In eyes, weak positive findings were observed in nerve fibers of retina between 3 and 10 days after the injection. In cornea, paraquat was localized in epithelial cells at the first 3 h and between 3 and 10 days after paraquat administration. Since skin occupies a vast area of the body in animals, as an organ, it seems to be an important storage pool for the redistribution of paraquat. PMID- 8345683 TI - Hymenoptera sting anaphylaxis: detection and clinical significance of individual bee and wasp venoms specific IgE and IgG4 antibodies. AB - In Japan, an average of 37 fatalities per year related to bee or wasp stings were reported during the years 1979-1988. To confirm fatal anaphylaxis serologically, we measured bee or wasp venom specific IgE (sIgE) and IgG4 (sIgG4) antibodies in the sera of 22 patients who visited hospitals with either allergic or anaphylactic reactions after bee or wasp stings by using Enzyme-Linked Immunosorbent Assay. Specific IgE or IgG4 antibodies against Polistes apachus (Paper wasp) and/or a mixture of Polistes annularis, P. exceramans, P. fuscatus, and P. metricus venoms of Polistes genus were detected in 11 patients and the detection frequencies were the highest among positive antibodies against bee or wasp venoms. The severity of allergic reactions was graded from 0-4 according to Mueller. The detection frequencies of sIgE in Mueller grade 0-3 patients were in the range of 33% to 67%, and in grade 4 were 100%. Whereas, the detection frequency of sIgG4 was high (67-100%) in grade 2-4 patients. Especially high levels of sIgE and sIgG4 were detected in patients experiencing the most severe clinical reactions. The detection of venom specific IgE and IgG4 antibodies appears to be useful when determining bee or wasp stings as the cause of fatalities. PMID- 8345684 TI - Analysis of hemoglobin in bloodstains using high-performance liquid chromatography. AB - Hemoglobin (Hb) extracted from bloodstains was investigated using cation-exchange high-performance liquid chromatography (HPLC). Among the HbA1 fractions, the amount of HbA1d increased linearly as the ages of the bloodstains increased, although the amount of HbA1c remained virtually unchanged. As HbA1 fractions are Hb modified with glucose or glycolytic intermediates, the total Hb were separated into glycated and non-glycated Hb fractions using affinity chromatography to investigate the effects of glucose on the age-induced Hb changes. The amounts of glycated Hb increased in proportion to the blood glucose level, and the increased glycated Hbs were eluted at retention times that corresponded to those of HbA1d and HbA0, although HbA1c peak area was virtually unchanged. The amounts of both glycated and non-glycated HbA1d increased with bloodstain aging, and the proportion of non-glycated HbA1d relative to the total HbA1d was greater than that of glycated HbA1d. These findings show that glucose has little effects on the elevation of HbA1d in bloodstains that occurs as they age. Furthermore, measuring HbA1d levels in bloodstains using HPLC may prove useful for the determination of their ages. PMID- 8345685 TI - [Determination of benzodiazepines by thermospray liquid chromatograph-mass spectrometer. Part 1. Nitrazepam, estazolam, bromazepam, flunitrazepam]. AB - Thermospray liquid chromatography mass spectrometric method is described for the determination of the benzodiazepines (Nitrazepam, Estazolam, Bromazepam, Flunitrazepam). Reversed-phase liquid chromatography was performed using a 15 cm Shim-pack CLC-ODS (Shimadzu) column, with acetonitrile-water (40:60) + 0.1 M ammonium acetate as mobile phase, at a flow rate of 1.0 ml/min. The temperature of the vaporizer, block and TH of the source block were 166, 270 and 275 degrees C, respectively. Positive ion thermospray mass spectra by thermospray ionization (TSP ionization) mode or thermospray on filament ionization (filament-on ionization) mode were obtained. Formation of the MH+ ion was observed as a base peak under TSP ionization and filament-on ionization conditions and fragment ions were very few. On both ionization mode, peaks representing nitrazepam as MH+ at m/z 282 at a retention time (R.T.) of 6.4 min, from estazolam as MH+ at m/z 295 at an R.T. of 6.4 min, from bromazepam as MH+ at m/z 316 at an R.T. of 4.5 min and from flunitrazepam as MH+ at m/z 314 at an R.T. of 8.8 min. The detection limit for all the benzodiazepines under investigation was less than 0.5 ng (S/N = 9.4 +/- 4.6) using selected ion monitoring. PMID- 8345686 TI - [Concentration of serum proteins and blood group substances in human saliva. 1. Quantitation method and variation of secreting quantities among daily life]. AB - Immunoelectrophoretic analysis of 100 times concentrated human saliva specimens showed marked individual differences in the content of albumin (Alb), IgA, IgG and transferrin (Tf). We concluded that the planimetric measurement of the precipitated area produced by latex-agglutination or hemagglutination on microtiter plates was an appropriate method for quantitating these serum proteins or ABO and Lewis blood group substances in saliva. Nonspecific agglutinating activity caused by mucinous substances in saliva was prevented when the saliva was once stained on a filter paper then dried and extracted with a buffer solution. Quantities of the serum proteins and blood group substances in saliva decreased immediately after meals and gradually increased 2 to 3 hours thereafter. The ratios of IgA/Alb, IgA/IgG and IgG/Alb did not differ remarkably with the time of sample collection. Saliva from parotid and submaxillary sublingual glands contained similar quantities of the serum proteins, whereas more ABO and Lewis blood group substances were found in saliva from submaxillary sublingual glands than in that from parotid gland. PMID- 8345687 TI - [Application of fuzzy inference to personal identification--sex determination from teeth]. AB - Fuzzy inference has received much attention recently as a new type of computer control technology for application in various fields. In this study I applied fuzzy inference to personal identification in medical jurisprudence. Sex determination program was constructed from teeth using the fuzzy inference technique and was compared with known discriminant analysis. The materials examined were mandibular and maxillary dental plaster models of 100 adult males and females, and 80 infant males and females. For the permanent teeth, measurements were made on crown width and thickness of the mandibular and maxillary central incisors, canines, first premolars, and first molars, and of the width and length of the maxillary dental arch. For the deciduous teeth, measurements were made on crown width and thickness of all teeth. Stepwise discriminant analysis was conducted using these values. The values from 5 selected upper-ranked items were set as input objects of the fuzzy inference program and the probability of maleness obtained from the discriminant analysis was set as the output object. Finally, sex determination program for both permanent and deciduous teeth was constructed using a fuzzy inference software development tool. Each measured value was input into this program and the output results were compared with those of discriminant analysis. The percentages of correct determinations for permanent teeth were 83.0% for males and 86.0% for females using stepwise discriminant analysis, however it increased to 93.0% for males and 89.0% for females using the fuzzy inference program. The percentages of correct determinations for deciduous teeth models were 67.5% for males and 75.0% for females using stepwise discriminant analysis, and increased to 86.3% for males and 81.3% for females using the fuzzy inference program. Among samples with probabilities between 40% and 60%, 3 out of 14 males and 4 out of 13 females were misjudged using stepwise discriminant analysis in cases of permanent teeth. However using fuzzy inference program, it reduced to 0 for males and 3 for females. In case of deciduous teeth, 9 out of 20 males and 9 out of 23 females were misjudged using stepwise discriminant analysis. But it reduced to 5 for males and 4 for females using the fuzzy inference program. PMID- 8345688 TI - [AIDS epidemic and infection control in the United States]. AB - AIDS is the second leading cause of death among persons 25-44 years of age. The risk to patients from physicians and other health care workers with HIV infection has also become a great public concern. There are no specific procedures for infection control in AIDS. Universal precautions are applied to AIDS as well as to any other infectious diseases. Recommended universal infection control in autopsy room is as follows: 1. Wear protective masks and eyewear (or face shields), laboratory coats, gloves, and waterproof aprons; 2. Develop and consistently practice the skills necessary to avoid penetrating injuries; 3. Decontaminate instruments and work areas contaminated during postmortem procedures with a 1:10 dilution of common household bleach, whose active ingredient is sodium hypochlorite; 4. Dispose of waste contaminated with body fluids into a red trash can indicated "BIOHAZARD". In case of accident such as needlestick or cut during autopsy of HIV infected corpe, the person should have the HIV antibody test and start taking azidothymidine (AZT) within 24 hours. PMID- 8345689 TI - [Evaluation of 99mTc-HM-PAO thigh accumulation in patients with cerebro-vascular disease]. AB - 99mTc-HM-PAO cerebral SPECT and whole body scintigraphy (WBS) were performed in 5 patients without cerebro-vascular disease (CVD) (Group 1), 31 patients with CVD but not hemiparesis (Group 2) and 18 patients with CVD and hemiparesis (Group 3). Four ROIs were drawn manually around the whole body (WB), brain (Br), right and left thigh (Th). We calculated some ratios: the total counts in the brain over the total counts in the whole body (Br/WB), the total counts in the thigh over the total counts in the whole body (Th/WB) and the mean counts in the thigh over the mean counts in the brain (Th/Br). The Br/WB was 6.9 +/- 1.8%, rt-Th/WB was 4.9 +/- 2.1%, lt-Th/WB was 5.1 +/- 1.3% and Th/Br was 0.46 +/- 0.17 in group 1. Whole body scintigraphies in group 1 revealed clear and similar images between right and left thigh. The Br/WB was 6.7 +/- 1.4%, Th/WB of paretic side was 4.6 +/- 1.0%, Th/WB of non-paretic side was 5.8 +/- 1.2% and Th/Br was 0.47 +/- 0.18 in group 3. The Th/WB in non paretic side was significantly higher than that in paretic side (p < 0.01). The thigh images in group 3 revealed clearly different between paretic and non-paretic thigh. In conclusion we could acquire the clear thigh images with 99mTc-HM-PAO. It was possible that we evaluated not only cerebral perfusion but also muscle atrophy and/or perfusion in patients with CVD using 99mTC-HM-PAO. PMID- 8345690 TI - [Transient ischemic dilatation of the left ventricle observed on dipyridamole stressed thallium-201 scintigraphy]. AB - To assess clinical significance of transient ischemic dilatation of the left ventricle (TID) on dipyridamole-stressed 201Tl myocardial scintigraphy, 110 patients suspected with coronary artery disease, including 13 with normal coronary, 48 with single vessel disease, 30 with 2 vessel disease, and 19 with 3 vessel disease were analyzed. TID was visually and quantitatively assessed calculating the ratio of the area within the left ventricular region on the initial and delayed image (TID ratio). TID was observed in 3 of 1 vessel disease (6%), 5 of 2 vessel disease (17%), and 8 of 3 vessel disease (42%). None of normal coronary artery showed TID. In patients with multivessel disease (MVD), TID was observed more frequently (27%) than in patients with 1 vessel disease (6%) (p < 0.025). Furthermore, the TID ratio tended to be higher (1.15 +/- 0.11) than those with single vessel disease (1.03 +/- 0.03). To identify patients with MVD, TID had a sensitivity of 27% and a specificity of 95%. ECG changes were observed more often in patients with TID than those without TID. Five patients showing TID underwent coronary artery bypass graft surgery, TID disappeared postoperatively in each patient. In conclusion, TID on dipyridamole 201Tl scan seems to be a specific although not sensitive marker for detecting MVD. PMID- 8345691 TI - [Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patients with brain tumor]. AB - In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtained by intraarterial infusion of 18.5 MBq of 99mTc-HMPAO. Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supraor infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99mTc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99mTc HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99mTc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99mTc HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherapy. PMID- 8345692 TI - [Increased lung uptake and transient left ventricular dilatation at stress myocardial scintigraphy with 99mTc-MIBI]. AB - On exercise 201Tl scintigraphy in coronary artery disease, left ventricular transient dilatation (LVTD) and increased lung uptake were noted as a marker of multivessel critical stenosis. To compare the two markers of 99mTc methoxyisobutyl isonitrile (MIBI) and 201Tl, planar and SPECT myocardial scintigraphy were performed with both radiopharmaceuticals in 27 patients with ischemic heart disease. Lung uptake (lung/max myocardial ratio) of MIBI was significantly lower than that of 201Tl, but the relationship of the lung uptake was linearly correlated (r = 0.77). The LVTD ratio (mean radial ratio = m-RR) was determined by the mean radius of the immediate postexercise short axial image by that of rest (redistribution) image. There was no significant correlation between the m-RR of 201Tl and that of MIBI (r = 0.27). We suggest that the mechanism of LVTD is due to not only subendmyocardial ischemia but also another factors. PMID- 8345693 TI - [Clinical application of 11C-NMSP to the patients with pituitary adenoma other than prolactinoma]. AB - The existence of dopamine D2 receptors in the pituitary adenoma is an important factor for bromocriptine therapy. In order to evaluate the D2 receptors in the pituitary adenoma, 11C-N-methylspiperone (NMSP) and positron emission tomography was performed in a variety of pituitary adenomas other than prolactinoma. Eight patients with pituitary adenoma including four non-functioning adenomas, two growth hormone (GH) secreting adenomas, one ACTH secreting adenoma and one TSH secreting adenoma and ten normal healthy volunteers were examined. 740 MBq of 11C NMSP was injected and dynamic scan was performed from the time of injection to 80 min postinjection. The time dependent regional radioactivity in the striatum (st) and in the tumor tissue (tm) was measured and the binding rate, alpha, was calculated according to the following equation: Cst, tm/Ccbl = alpha x integral of t0 Ccbl dt/Ccbl + 1. The ratio of total radioactivity in the striatum or tumor over total activity in the cerebellum was plotted versus "normalized time", which was obtained by dividing integrated cerebellar radioactivity by actual cerebellar radioactivity for each timepoint. In three patients with pituitary adenoma, two scans were performed before and three hours after oral intake of 2.5 mg of bromocriptine. The alpha values for pituitary adenoma and normal striatum were 0.031 +/- 0.023 (0.017-0.088) and 0.042 +/- 0.006 (0.034-0.049), respectively. Bromocriptine reduced alpha value to various degree in pituitary adenoma (13-56%) but not in striatum (-3.7-3.3%). Our data suggests that in some of pituitary adenoma other than prolactinoma, dopamine D2 receptors existed but that nonspecific binding also contributed to the radioactivity in the tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345694 TI - [Relation between uptake of 67Ga-citrate in salivary glands and irradiation doses]. AB - A retrospective study is performed 67Ga-citrate uptake by scintigraphy to evaluate the relation between gallium uptake of salivary glands and radiotherapy with special reference to radiation dose and period after initial irradiation. Sixteen patients with radiotherapy to their head and neck regions were studied, undergone 67Ga scintigraphy for four times or more were investigated. The following results were obtained: 1. About half of the total number of salivary glands increased the uptake of 67Ga-citrate during radiotherapy. 2. The number of salivary glands which increased uptake in a group which received more than 30 Gy was greater than that in a group less than 30 Gy, and many of them remained with increased activity for one year after radiotherapy. 3. Uptake in glands that received dose less than 30 Gy showed rapid increasement initially, and showed decrease of uptake in six months after the irradiation. We concluded that there was different tendency of gallium uptake between a group of patient with irradiation of less than 30 Gy and that with irradiation of more than 30 Gy. It is suggested that we must always consider gallium uptake of salivary glands for long term after the radiotherapy, when we discuss the recurrence or metastases of neck lymph nodes of patients, who have performed radiotherapy to their head and neck regions, especially high dose irradiation. PMID- 8345695 TI - [Usefulness and safety of dobutamine stress thallium myocardial scintigraphy]. AB - Pharmaceutical stress test is performed for diagnosis of coronary artery disease in patients who can not perform exercise test. We studied whether high dose dobutamine stress test is useful and safe. Subjects consisted of 133 patients (pts) in doubutamine stress test and 45 pts in exercise test. Dobutamine stress test was initiated by 10 micrograms/kg/min, followed by 10 micrograms/kg/min increment every 3 minutes. Maximal doubutamine dose was 40 micrograms/kg/min for 3 minutes. Endpoints of dobutamine stress were as follows: ST depression equal to or more than (> or =) 0.2 mV: 30 pts, > or = 75% predictive maximum heart rate: 20 pts, > or = 20 mmHg systolic blood pressure fallen: 10 pts, 40 micrograms/kg/min for 3 minutes: 10 pts, chest pain: 7 pts, pressure rate product (PRP) > or = 25,000: 1 patient. Side effects of dobutamine stress test were as follows: palpitation: 52%, arrhythmia: 13%, angina and dyspnea: 7%, headache: 6%. These symptoms were disappeared within 2 minutes. One patient, who performed dobutamine test 2 day after PTCA, had myocardial infarction. At peak of dobutamine stress test, systolic blood pressure, heart rate and PRP were increased similar to exercise test. However, diastolic blood pressure was not changed. The concentration at peak of dobutamine was 25.5 +/- 7.8 micrograms/kg/min. The duration of dobutamine stress test was 7.3 +/- 2.3 minutes. The 65 patients (49%) need more than 20 micrograms/kg/min of dobutamine which was maximal loading dose in previous reports. For diagnosis of coronary artery disease, sensitivity was 91% (31/34) and specificity was 70% (7/10). From these data, high dose dobutamine stress test is useful and relatively safe stress method for diagnosis of coronary disease. This stress test would be performed in patients who can not perform exercise test. PMID- 8345696 TI - [99mTc-HMPAO SPECT in the brain death--a case report]. AB - Brain single photon emission computed tomography (SPECT) with 99mTc-d,l hexamethyl-propyleneamine oxime (HMPAO) was performed twice in a 78-year-old man clinically diagnosed as brain death according to the standard criteria of the Japanese Ministry of Welfare. The first brain SPECT demonstrated the tracer accumulation in the brain, indicating preserved cerebral blood flow. The second brain SPECT performed 3 days later revealed cessation of the blood flow. In patients with preserved cerebral blood flow, the diagnosis of brain death cannot be made, even if they meet the existing criteria, because previous report noted the recovery in some of those patients. Brain perfusion SPECT plays an important role as a confirmatory test for the diagnosis of the brain death. PMID- 8345697 TI - [Detection of myocardial ischemia by 99mTc-Teboroxime myocardial SPECT: a comparison with 201Tl myocardial SPECT]. AB - Exercise myocardial SPECT using 99mTc-Teboroxime was performed and the regions of ischemic area were compared with 201Tl myocardial SPECT in 8 patients with coronary artery disease. All patients had no evidence of previous myocardial infarction, and underwent bicycle ergometer exercise according to a standardized multistage exercise protocol. At peak exercise, 555 MBq 99mTc-Teboroxime or 75 MBq 201Tl was injected intravenously. After termination of exercise, images were obtained with a gamma camera rotating through a 180 degrees arc from 45 degrees right anterior oblique to 45 degrees left posterior oblique. The concordance of 99mTc-Teboroxime SPECT and 201Tl SPECT was 63% in ischemic region and 83% in normal region. Furthermore, one patient underwent dipyridamole infusion and 99mTc Teboroxime SPECT was carried out. The images obtained by dipyridamole 99mTc Teboroxime SPECT were equivalent to the images of exercise 201Tl SPECT. 99mTc Teboroxime SPECT seems useful for the detection of the coronary artery disease. It was suggested that evaluation of the myocardial viability in acute phase of myocardial infarction can be possible by using 99mTc-Teboroxime SPECT. PMID- 8345698 TI - [Assessment of reverse redistribution on exercise 201Tl myocardial SPECT in patients with hypertrophic cardiomyopathy]. AB - Reverse redistribution is revealed on exercise 201Tl myocardial SPECT in some cases with hypertrophic cardiomyopathy. Ten patients with hypertrophic cardiomyopathy without coronary artery disease who showed reverse redistribution visually were studied. Reverse redistribution was evaluated by the early and delayed images of exercise 201Tl myocardial SPECT. Relation between reverse redistribution and distribution of left ventricular hypertrophy estimated by echocardiography and magnetic resonance imaging was investigated, and the mechanism of reverse redistribution was analyzed by referring to Bull's eye display of washout rate. Reverse redistribution was displayed in non-hypertrophic region and washout rate was normal in that region and low in hypertrophic region. In conclusion, in order to interpret reverse redistribution it is necessary to recognize hypertrophic region and to refer to washout rate. PMID- 8345699 TI - [Assessment of the background count to measure the left ventricular ejection fraction with a nuclear stethoscope]. AB - The nuclear stethoscope is a newly developed device for monitoring left ventricular ejection fraction (EF) with a pair of cadmium telluride detector for both left ventricular count (first channel) and background count (second channel). Although it is useful for evaluating the cardiac function during exercise, the methodology of the calculation for distinguishing the net ventricular blood count from the background count has not been established yet. In order to establish a reasonable method to calculate EF, we measured EF using a nuclear stethoscope and conventional gated blood pool scintigraphy in 20 healthy volunteers. All subjects underwent two supine ergometer exercise tests consisting of the 3 stages for the nuclear stethoscope and blood pool scintigraphy. The EF was determined with the following three method for the nuclear stethoscope; 1) Cut-off level was fixed at 70% of first channel, 2) Cut-off level at 75%, 3) Cut off level was determined by the background count obtained from second channel. There was a poor relationship between the EFs obtained from gated blood scintigraphy and the EFs from the nuclear stethoscope calculated by any of these method. Regarding the EF calculated using the background count, however, the delta values of EF between rest and any of the 3 stages during exercise correlated closely to those EF from blood scintigraphy. When we apply the EF-at rest value obtained from blood pool scintigraphy to analysis with the nuclear stethoscope, the EFs of 3 stages indicated good correlation (Stage I r = 0.91, Stage II r = 0.82, Stage III r = 0.69).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345700 TI - [Analysis of cells in bronchoalveolar lavage and ultrastructure of lung tissues in experimental silicosis]. AB - Sprague-Dawley rats received intratracheal instillation of 50 mg silica dissolved in 1 ml saline. Animals were killed by intraperitoneal injection of nembutal at periods between 0.5 hour and 4 months. Analysis of bronchoalveolar lavage (BAL) cells and histological and ultrastructural studies were performed on the right and left lungs, respectively. A large number of neutrophils was recovered in BAL fluid from 3 hours after silica infusion, and was maintained until 4 months as the silica stimulus remained in the lung tissues. The absolute number of lymphocytes gradually increased in BAL fluid from day 2. The recovery of macrophages was quite low 24 hours after silica instillation. In contrast, massive aggregates of macrophages were forming silica granulomata in the lung tissues. This discrepancy of results between cells obtained from BAL and those in the lung tissues was caused by an impaired capacity of migration of alveolar macrophages by the development of a junctional apparatus, the "subplasmalemmal linear densities (SPLD)". These structures consisting of hemidesmosome-like unpaired and desmosome-like paired ones infrequently appeared in the acute stages of granuloma formation and were quite common in macrophages and epithelioid-like cells in granulomata 2 weeks after instillation and thereafter. Silicotic granulomata grew in the alveolar ducts from the aggregates of macrophages superimposed on a various number of alveolar sacs. Regeneration of type II alveolar epithelial cells and bronchiolar cuboidal cells usually covered the outer border of the granuloma. Endothelial cells of alveolar capillaries regenerated following recurrent injuries, and only occasionally formed a fenestration structure in their cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345701 TI - [Epidemiological study of snoring--a questionnaire survey in factory workers]. AB - There has been no epidemiological study of snoring in Japan, and we therefore performed a questionnaire survey (in about 7,000 adult men working at a steel making factory at the time of the yearly health examination, and investigated the relationship between the severity of snoring and 17 items including age, obesity, family history of snoring, daytime hypersomnolence, hypertension, smoking, alcohol intake and traffic accidents. We classified all the subjects into three groups, no snoring, mild snoring, and severe snoring group. We defined severe snorers as persons who snored loudly in both inspiratory and expiratory phases and those who snored loudly with apnea. We found that aging, obesity, smoking and alcohol intake are risk factors for snoring. Compared with non-snorers, severe snorers were found to have a high incidence of family history of snoring, daytime hypersomnolence, and history of treatment of hypertension. No relationship was found between the severity of snoring and the occurrence of automobile accidents. The proportion of severe snorers over 40 years old with obesity, daytime hypersomnolence and morning headache was 0.25%, representing the group that may have obstructive sleep apnea syndrome. The probable incidence of sleep apnea syndrome in men may be considerably lower in Japan compared with that in either U.S.A. or Europe. PMID- 8345702 TI - [Effects of antioxidant enzymes in erythrocytes on pulmonary arterial pressure during hypoxic gas breathing]. AB - Using isolated rabbit lungs (n = 72) perfused at a constant flow of 70 ml/min, we analyzed whether the antioxidant system in erythrocytes significantly contributes to maintaining pulmonary vascular responsiveness to alveolar hypoxia (HPV) in normal lungs. As a measure of HPV, we observed the difference (delta P) between mean pulmonary arterial pressure during ventilation with normoxic gas mixture (21% O2, 5% CO2 in N2) and that during hypoxic gas breathing (3% O2, 5% CO2 in N2). Autologous erythrocytes obtained from the animals treated with various substances inhibiting either superoxide dismutase (SOD), the anion channel of the membrane, catalase (CAT) or glutathione peroxidase (GSH-Px). Subsequently, delta P was systematically measured in the perfusate, whose hematocrit was adjusted to 6-7% with normal or treated erythrocytes as described above. Further, the effects of adding SOD (75 U/ml) or CAT (1000 U/ml) to the perfusate on delta P were examined. The following results were obtained. (1) Inhibition of the superoxide scavenging mechanism in erythrocytes (SOD and anion channel) exerted no significant influence on delta P. (2) Inhibition of hydrogen peroxide scavengers in erythrocytes did not alter the scope of delta P. (3) Addition of either SOD or CAT to the perfusate did not show any significant effect on delta P. The findings are highly consistent with the idea that HPV in normal lungs is essentially independent of antioxidant enzymes in erythrocytes, which are expected to be one of the important factors determining the total capacity to deal with oxidant stress in the lung. PMID- 8345703 TI - [Effect of thromboxane A2 synthetase inhibitor (OKY-046) on leukotriene C4 induced airway hyperresponsiveness in guinea pigs]. AB - In this study, we investigated the effects of peroral (p.o.) administration of a thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on the airway hyperresponsiveness (AHR) in guinea pigs induced by intravenous administration of leukotriene C4 (LTC4). A 3 micrograms/kg/hr LTC4 infusion induced airway wall thickening (AWT) and AHR to 1.8 and 3.6 micrograms/kg histamine bolus shot. OKY 046 100 mg/kg p.o. partially inhibited the AHR induced by LTC4 without inhibition of AWT. Previously, we have reported that LTC4-induced AHR was partially inhibited, to the same exert as by OKY-046, by TXA2 receptor antagonists, ONO-NT 126 and ONO-8809. These data suggest that intravenous administration of LTC4 generates TXA2, and TXA2 augments LTC4-induced AHR partially in guinea pigs. PMID- 8345704 TI - [Determination of pulmonary blood flow by acetylene rebreathing method in patients with chronic respiratory disease]. AB - Non-invasive measurement of pulmonary blood flow by acetylene rebreathing was performed in patients with pulmonary diseases. Cardiac output measurement by thermodilution method was also used simultaneously. A fast computation system was coupled with the measurement. Fourteen emphysema patients and 7 pulmonary fibrosis patients were the subjects. Ten patients with normal lung function were normal controls. After the measurement of cardiac output, the subjects rebreathed mixed gas containing acetylene and argon from the end tidal level. The inspiratory and expiratory gas was measured by mass-spectrometer. A lung model made of two compartments connected in series, a compartment of the rebreathing bag and a compartment of the lung were used for the analysis, while taking account of the volume reduction due to O2 and CO2 exchange and the fluctuation of end tidal gas concentration until equilibrium between the bag and the lung was reached. Values in 9 emphysema cases and 6 fibrosis cases were within or near the 90% confidence limits of control. Five emphysema cases were obviously out of the range, and their pulmonary blood flow was less than the cardiac output and their mean arterial PCO2 was higher than that of the other emphysema cases. These cases were considered to have blood flow to the sites with low alveolar ventilation per unit volume. PMID- 8345705 TI - [Changes in bronchoalveolar cell profiles of asthma patients induced by long-term glucocorticoid therapy]. AB - Effects of long-term glucocorticoid therapy on airway inflammatory cells were examined in 40 patients with bronchial asthma. 1. The dose of glucocorticoids required by asthmatic patients tended to increase and the level of serum cortisol tended to decrease with prolongation of the period of glucocorticoid therapy. 2. The proportion and number of lymphocytes in bronchoalveolar lavage (BAL) fluid decreased with prolongation of the period of glucocorticoid therapy. The proportion of BAL lymphocytes in asthmatic patients treated with glucocorticoids for more than 5 years was significantly lower than that in those treated for less than 4.9 years. 3. The proportion and number of BAL neutrophils increased with prolongation of the period of glucocorticoid therapy and the proportion of BAL neutrophils in patients treated with glucocorticoids for more than 10 years was significantly higher compared with those treated for less than 9.9 years. These findings indicate that long-term glucocorticoid therapy induces changes in airway inflammatory cell profiles, with a decrease in the number of lymphocytes and increase in the number of neutrophils. PMID- 8345706 TI - [Contact time of red blood cells with alveolar air]. AB - The contact time between red blood cells and alveolar air is one of the most important factors affecting red blood cell oxygenation in the lungs. Many methods have been presented for contact time measurement, however, no work, evaluating it by tracing red blood cell movement through the pulmonary capillary network has been reported. In this study, the contact time was measured by tracing red blood cells, stained with fluorescein isothiocyanate (FITC-RBC), with a fluorescent microscope in living rat lung. It was assumed that the transit time of red blood cells through the pulmonary capillary network was equivalent to the contact time. The flow patterns of red blood cells were complicated, namely, FITC-RBC discharged from one arteriole flowed into several venules through many routes in the pulmonary capillary network, and those ejected from several arterioles pored into one venule. Furthermore, the FITC-RBC flow rate changed many times in the pulmonary capillary network. The contact time varied from 0 to 1.2 seconds. The measurement was performed in each classified route by the straight distance between arteriole and venule, in order to simplify the various capillary networks. The results revealed that the contact time was 0.3, 0.4, 0.5, 0.7, 0.7 and 0.7 seconds on the average respectively in the routes of 101--150, 151--200, 201--250, 251--300 and 301--350 microns straight distance. The frequencies of the above distance routes were 5, 8, 15, 23, 26 and 21%, respectively. As a result, the total lung contact time calculated using these frequencies was 0.7 +/- 0.2 seconds (mean +/- standard deviation) on average. PMID- 8345707 TI - [Case report of miliary TB, with mediastinal TB involving the aorta, trachea and esophagus with death due to hemorrhage from perforation of aorta into the esophagus during treatment]. AB - A 32-year-old male was diagnosed as having miliary tuberculosis in May 1990. In spite of antituberculosis chemotherapy, he developed tuberculous meningitis and intracranial tuberculoma in September 1990. Miliary shadows on chest X-ray disappeared in December 1990. However, he developed left atelectasis, and bronchofiberscopy revealed soft tumor in the left main bronchus in January 1991. He suddenly vomited large amounts of blood and expired in February 1991. At autopsy, tuberculous lymphadenitis and cavitation were noted in the mediastinum, through which the left main bronchus, esophagus and descending aorta communicated. The patient died of massive bleeding which resulted from the rupture of tuberculous aortitis into the esophagus. This is a very rare case of tuberculous aortic aneurysm rupturing into both the bronchus and esophagus. PMID- 8345708 TI - [A case of T-cell lymphoma showing marked bronchial invasion]. AB - We report a case of malignant lymphoma with bronchial involvement in a 35-year old male patient. On admission, chest X-ray revealed enlargement of bilateral hilar lymph nodes and expansion of the superior mediastinal space. CT and MR images showed that the tumor shadow appeared to wrap around the left and right main bronchi. Bronchoscopy revealed that the entire periphery of the left main bronchus was constricted. Transbronchial biopsy specimens, which revealed findings consistent with non-Hodgkin's lymphoma, were positive for surface markers of CD2, CD4, and CD8 and negative for those of CD19 and CD20. After MACOP B treatment, the patient entered complete remission. He received 41.4 Gy radiotherapy thereafter, and has shown no signs of recurrence during continuing follow-up. PMID- 8345709 TI - [Two cases of mediastinitis as a complication of odontogenic infection and tonsillitis]. AB - We experienced two cases of descending necrotizing mediastinitis with different etiology. Case 1: A 59-year-old woman presented with chief complaints of dyspnea and swallowing disturbance. She had been diagnosed as having tonsillitis one week before. She was very pyrexic, and laboratory examination indicated acute inflammation. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis to be a complication of tonsillitis. Case 2: A 54-year-old man had a tooth extracted 3 weeks prior to admission. His chief complaints were craniomandibular disturbance and neck swelling. Laboratory examination disclosed multiple organ failure and DIC. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis in this case to be a consequence of an odontogenic infection following tooth extraction. Both patients received continuous drainage and irrigation of the abscesses and recovered in about 2 months. Case 1 showed an impaired glucose tolerance after recovery from mediastinitis. Although the main causes of mediastinitis are cardiac surgery and esophageal perforation, our cases demonstrate that mediastinitis may occur as a complication of deep neck infection. PMID- 8345710 TI - [Home intermittent negative pressure ventilation in a case of chronic respiratory failure due to old tuberculous pleuritis]. AB - A 64-year-old male with a history of tuberculous pleuritis at age 29 had received home oxygen therapy since age 58 because of chronic respiratory failure. He was admitted with symptoms of dyspnea at rest and myoclonus at age 62. Because CO2 narcosis occurred twice, we performed intermittent negative pressure ventilation (INPV) after short-term positive pressure ventilation with transnasal intubation. He has received INPV for 7 hours every day at his home for 20 months without acute exacerbation of respiratory failure, and his activity of daily life subsequently improved. In conclusion, INPV seems to be useful for patients with chronic hypercapnic respiratory failure due to lung disease. PMID- 8345711 TI - [A case of limited form of Wegener's granulomatosis without detection of anti neutrophil cytoplasmic antibody]. AB - A 52-year-old woman was admitted to our hospital because of high fever and productive cough. Her chest X-ray showed multiple cavitary nodules in both lungs. Although we suspected Wegner's granulomatosis (WG), anti-neutrophil cytoplasmic antibody (ANCA) was not detected in her serum. Finally, an open lung biopsy was performed, and the limited form of Wegener's granulomatosis was diagnosed. With cyclophosphamide and steroid treatment, she markedly improved. We conclude that in patients suspected of having WG, it is necessary to perform open lung biopsy regardless of the detection of ANCA. PMID- 8345712 TI - [A case of status asthmaticus complicated by with pneumoperitoneum during mechanical ventilation therapy]. AB - A 46-year-old woman was admitted to our hospital for a severe asthma attack. On admission, systemic cyanosis was observed, and her consciousness state was drowsy. Arterial blood gas showed severe respiratory acidosis, hypoxia, and hypercapnea, with pH, PaO2, and PaCO2 of 7.163, 29.9 torr and 81.3 torr, respectively. Immediately, mechanical ventilation was commerced but on the third hospital day pneumomediastinum and subcutaneous emphysema appeared, and on the sixth day pneumoperitoneum also appeared. The chest CT scan on the sixth day showed free air around bilateral internal mammary vessels. This indicated that air moved from the mediastinum into the peritoneal cavity through an anterior route, via the sternocostal triangle formed by the xiphoid origins of the diaphragm medially and the costal origins laterally. PMID- 8345713 TI - [Analysis of bronchoalveolar lavage fluid in a case of high altitude pulmonary edema]. AB - A 29-year-old male climber developed high altitude pulmonary edema (HAPE), progressing from headache and dyspnea to disturbance of consciousness in the Japan Alps. He was admitted to Shinshu University Hospital. Physical examination on admission revealed a cyanotic patient with coarse crackles and wheezes in bilateral lungs. Chest X-ray film showed bilateral patchy infiltrates. Arterial blood gases indicated severe hypoxemia, and respiratory alkalosis; pH 7.452, PO2 35.5 Torr, PCO2 31.6 Torr. Right heart catheterization showed noncardiogenic pulmonary edema, analysis of bronchoalveolar lavage (BAL) fluid was as follows; cells 2.05 x 10(5)/ml (alveolar macrophages 61.5%, neutrophils 25.5%, lymphocytes 13.0%), protein concentration 91 mg/dl. Cellular and protein analysis of BAL has been shown to be of value to clarify the pathogenesis of the permeability edema in patients with HAPE. PMID- 8345714 TI - [A case of adenocarcinoma presenting as a cavitary lesion with niveau formation]. AB - Primary pulmonary adenocarcinoma rarely shows cavitation with a fluid level on chest roentgenograms. Herein we describe such a case misdiagnosed as pulmonary tuberculosis. The patient was a 63-year-old, female who had never smoked. Chest roentgenograms revealed a cavitary lesion in the left lower lobe, possessing a prominent fluid level. Fiberoptic bronchoscopic aspirate was positive for acid fast bacilli on stains. Since there was no improvement with antituberculous chemotherapy, a left lower lobectomy was performed. The present case is of interest in the light of cavity formation in pulmonary carcinoma. The diagnosis and roentgenographic features are discussed. PMID- 8345715 TI - [A case of primary pulmonary artery sarcoma]. AB - A 39-year-old male was admitted with persistent cough, palpitations and dyspnea on exertion. Chest X-ray showed cardiomegaly, left pleural effusion and left hilar mass shadow. Echocardiogram revealed dilatation and hypertrophy of the right atrium and ventricle. Perfusion lung scintigram disclosed a complete defect of the left lung and a partial defect of the right upper lobe. CT scan showed an intravascular tumor mass in the bilateral main pulmonary arteries. Digital subtraction angiography of the pulmonary artery revealed complete obstruction of the left pulmonary artery and stenosis of the right pulmonary artery. MR image showed intravascular tumor infiltrating the mediastinum and surrounding tissue. Sarcoma was highly suspected, but a histopathological diagnosis could not be made. The patient died of heart failure two months after admission to our hospital. Postmortem examination showed that the pulmonary trunk and left main pulmonary artery were markedly dilated and completely occluded by the tumor. Tumor infiltrated into the left upper lobe and mediastinal lymph nodes. The tumor was histologically diagnosed as undifferentiated sarcoma. PMID- 8345716 TI - [A case of small-sized lung adenocarcinoma, 4 mm in diameter, detected by CT]. AB - A 67-year-old woman presented to our hospital because of an abnormal shadow on her chest X-ray film. The film showed a well-circumscribed nodule, 15 mm in diameter, in her left lower lung field. Compared with her prior film of 1.5 years ago, the size of the nodule had not changed, suggesting the possibility of a benign lung tumor. Chest CT with 10 mm-thick collimation demonstrated another small round opacity near the nodule in the left lower lobe; this small opacity was not detectable on plain chest films. For further analysis of the small opacity, high resolution CT was carried out. High resolution CT with 1.5 mm collimation showed a 4 mm nodule with an ill-defined margin and relatively low internal density, and probable involvement of a peripheral branch of the pulmonary vein. These features suggested the possibility of malignant characteristics of this small opacity. The patient underwent thoracotomy and pathologic examination revealed that the large well-circumscribed nodule was a hamartoma and the small nodule was a papillary adenocarcinoma lesion. High resolution CT is prerequisite to diagnosing the characteristics of small pulmonary nodules. PMID- 8345717 TI - [Shock wave therapy of the rabbit VX2 bladder cancer--THP-ADM concentration in the tissue after combination therapy of THP-ADM and shock wave]. AB - Tissue concentration of THP-ADM was analysed after the administration of THP-ADM with or without exposure of high energy underwater shock waves (SW) to rabbit bladder VX2 cancer. THP-ADM was administered intravenously (2 mg/kg) or into the urinary bladder (10 mg/body). After the administration of THP-ADM, SW was exposed (6,000-10,000 shots) to VX2 bladder cancer or normal bladder tissue. One hour later, THP-ADM tissue concentration was measured by high performance liquid chromatography method. In intra-venous group, THP-ADM concentration of cancer tissue was significantly lower (p < 0.02) in SW group than that of non-SW group. In bladder instillation group, THP-ADM concentration of normal bladder tissue was significantly higher (p < 0.02) in SW group than that of non-SW group and the average concentration of cancer tissue was higher about three times in SW group than that of non-SW group. PMID- 8345718 TI - [Tumor recurrence and grade and/or stage progression in low grade tumor. Analysis of 154 patients with superficial transitional cell carcinoma of the bladder]. AB - The clinicopathological findings of 154 patients with initially superficial (stage pTa or pT1) transitional cell carcinoma in the bladder were analyzed to study risk factors for tumor recurrence or progression in grade and/or stage of the low grade tumor. The number, size, grade and stage of tumor at the first presentation were the significant predictors for the first tumor recurrence. However, only the tumor grade and size at the first recurrence were the predictors for the second recurrence. In 19 (33%) of 57 patients with recurrence, low grade superficial tumor progressed in tumor grade and/or muscle invasion. The progression of low grade tumor correlated with short tumor free intervals and tumor size. Grade and/or stage progression was observed in 14% of the tumor of 1 cm or less in diameter, whereas in 42% of the tumor more than 1 cm in diameter (Chi-square test: p < 0.25). These results indicate that tumor grade and size are important predictors for recurrences. Short tumor free intervals and sizes of tumors in the second recurrence are significant predictors for grade and/or stage progression in low grade superficial cancer. PMID- 8345719 TI - [Establishment and characterization of a new human renal cell carcinoma cell line (KG-2) and metastatic model in nude mice]. AB - A new cultured cell line (KG-2) derived from human renal cell carcinoma and a metastatic model in nude mice were studied. KG-2 was cultured from renal cell carcinoma (clear cell carcinoma) of the left kidney. In vitro doubling time of KG 2 was approximately 50 hours. KG-2 cells produced tumors in both the subcutaneous and renal sub-capsular space in nude mice, with tumorigenicity of 75%, showing no difference between the two sites. Histologically, tumors formed in the subcutaneous sites were hypovascular granular cell carcinoma. Moreover, each tumor was encapsulated by a thick fibrous capsule and never produced distant metastasis or invasion into the surrounding tissue. However, tumors formed in the subrenal capsular space were clear cell carcinoma. These tumors were hypervascular, and produced distant metastases. The most common metastatic site was the lung. Immunohistochemical analysis using anti-human collagenase type IV antibody on tumors formed in subcutaneous and subrenal capsular sites demonstrated that the expression of this enzyme in tumors formed in the subrenal capsular space was much higher than that in tumors formed in the subcutaneous site. Additionally, immunohistochemical study using anti-mouse collagen type IV antibody, a major components of the vascular wall, demonstrated many small densely growing vessels in tumors formed in the subrenal capsular space. In contrast, few vessels were produced in tumors formed in subcutaneous sites. These findings suggest that factors relating to the different injection sites may regulate the production of collagenase type IV secreted by KG-2 cells and neovascularity in nude mice. This metastatic model may be useful in the study of the mechanism of cancer metastases. PMID- 8345720 TI - [Expression of HLA class II antigen-associated invariant chain on renal cell cancer]. AB - Major histocompatibility complex (MHC) antigens play important roles in immune responses. MHC class II molecules serve as restriction elements for cells presenting antigens to CD4-positive helper T-cells. They also function as histocompatibility antigens responsible for graft rejections by stimulating allogenic reaction. Furthermore, it was reported that the expression of class II antigen on tumor cells increases immunogenicity in mice by a mechanism involving class II molecule positive tumor cells which present tumor associated antigens to host immune cells or induce allogenic reactions against tumor cells. Class II molecules associate with the HLA class II antigen-associated invariant chain (Ii) as soon as class II molecules are produced in the rough endoplasmic reticulum. Ii is considered to block the binding of endogenous peptides to class II molecules, and to be a signal for transporting class II molecules to endosomes. Both functions of Ii are essential for the function of class II molecules. To investigate the association between renal cell cancer (RCC) and the host's immune system, we immunohistochemically examined 60 RCCs for the expression of Ii, class II and class I antigens on RCC and the degree of lymphocytic infiltration. We detected Ii to varying degrees on 53 out of 60 RCC tissues but none on normal renal tubular cells. Compared with class II antigens, they were detected in the order DR > or = Ii > or = DP not equal to DQ. A significant correlation was found between the expression of Ii and the degree of lymphocytic infiltration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345721 TI - [Evaluation of vasculogenic erectile impotence using DICC (dynamic infusion cavernosometry & cevernosography) with intracavernous injection of papaverine]. AB - Dynamic infusion cavernosometry and cavernosography (DICC) with intracevernous injection of papaverine was performed in 28 men. The change of the corporal body pressure after injection of papaverine and the intracavernous pressure decrease within the first 30 seconds after discontinuation of saline infusion were observed. Four different patterns of cavernometric findings can be identified on the basis of the intracavernous pressure behavior in response to injection of papaverine, infusion of saline and discontinuation of infusion: pattern A represents no vasculogenic insufficiency, pattern B represents pure arterial insufficiency, pattern C clearly represents venous leak and pattern D represents venous leak and arterial insufficiency. Cavernosography has found out effectively the sites of venous leakage in most our cases. PMID- 8345722 TI - [Detection of numerical chromosome aberrations in urologic malignancies using in situ hybridization from formarin-fixed paraffin sections]. AB - It has been shown that molecular cytogenetics in interphase nuclei is applicable to paraffin embedded sections from formarin-fixed materials utilizing in situ hybridization (ISH). This allows precise identification of numerical abnormalities of chromosome in tumor cells without disruption of tumor morphology. Thirteen cases of bladder cancer and twenty six cases of prostate adenocarcinoma were evaluated for numerical aberrations of chromosome 1, 7, 10, 11, 17, 18, X and Y utilizing biotinylated probes specific for the alpha satellite region. In two cases from total prostatectomy, one case from total cystectomy and two cases from TUR-P specimen, hybridized chromosomes could not be detected in individual tumor cells. With respect to the appearance of the ISH signal, optical concentration and time for the digestion enzyme has to be established essentially. This technique can now be applied on the detection of biological activity in various types of urological cancer. PMID- 8345723 TI - [Anticholinergic therapy of urinary incontinence and urinary frequency associated with the elderly--with special reference to dementia]. AB - Pharmacotherapy with anticholinergic agents was studied in a total of 80 patients aged 65 years or older with chief complaints of urinary frequency (4 patients) and/or ugency incontinence (76 patients). The subjects were 45 men and 35 women at the age ranging between 65 and 92 (mean 73.7). The patients received anticholinergic agents (terodiline hydrochloride 24 mg/day, oxybutynin hydrochloride 6 mg/day, propantheline bromide 60 mg/day separately or in combination) for more than two weeks. Subjective symptoms and objective findings were assessed before and after the administration. In addition, according to the result of Hasegawa's dementia rating scale the patients were divided into dementia group and non-dementia group for further evaluation of the study drugs. As a result, cystometrogram revealed significant increase of maximum bladder capacity in either dementia group or non-dementia group. There was no significant difference in rate of objective improvement between both groups. On the other hand, rate of subjective improvement was significantly higher in non-dementia group (40%) than in dementia group (15%). As mentioned above, improvement of cystometrogram findings was not associated with improvement of subjective symptoms in the demented patients. This suggests that the major cause of incontinence in demented patients is not the bladder dysfunction but the specific conditions of demented patients such as agnosia and apraxia. PMID- 8345724 TI - [The clinical significance of carbohydrate antigen 19-9 (CA19-9) in transitional cell cancer of urinary tract]. AB - For the purpose of evaluating the utility of CA19-9 determination in transitional cell cancer (TCC) of the urinary tract, its serum value, tissue level and, immunohistochemical study, and follow up study, with high serum value were examined in 43 cases with TCC and 13 cases of control. 1. Serum values were 19.1 U/ml in the control group and 198 U/ml in the tumor group. Though those of tumor were higher than those of the control group, there is no statistical difference between both groups. The cases with abnormally high value were observed in 13.7% of the control group, 13.8% of the bladder cancer, and 57.1% of the upper urinary tract cancer. 2. Tissue levels were 816 U/g wet tissue in the control group and 13,000 U/g wet tissue in the tumor group, showing a significantly higher value (p < 0.01) in the tumor group, statistically. 3. Immunohistochemical study were positive in 4.0% of the control group and 88.4% of the tumor group. 4. There is a significant correlation between serum values and tissue levels (p < 0.05, r = 0.483). 5. The serum values did not correlated with the staining property, tumor size, grade, and stage. 6. The tissue levels correlated with the tumor size, but did not correlate with the staining property, grade, and stage. 7. In the follow up study of cases with high value, those, who had not attained postoperative normalization, died of recurrent carcinoma. In cases showing an elevation despite postoperative normalization, too, all showed recurrence. Only those, whose value were normalized and remained at the normal range, are living without metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345726 TI - [Transrectal hyperthermia for chronic prostatitis]. AB - Transrectal hyperthermia was performed on 13 patients with chronic non-bacterial prostatitis which failed to respond to the conventional treatments. We used "Prostathermer" (Biodan-Medical system, Israel) for heating the prostate gland. The prostate was heated at 42 degrees C-43 degrees C, for 60 minutes in 1 session. Treatment consisted of 6 sessions, and was performed during a period of three weeks on an outpatient basis. Of 11 patients re-evaluated after 3 months, 6 (55%) achieved improvement of subjective symptoms. Of 9 patients, 4 (44%) showed reduction of the number of white blood cells (> or = 10 leukocytes count per high power field) in their expressed prostatic secretion (EPS), which however was not always correlate with improvement of subjective symptoms. No complications were encountered in our series. Our result indicates that local hyperthermia is safe, and would become new modality in the treatment for chronic prostatitis. PMID- 8345725 TI - [Active uptake of oxalate in a renal tubular cell line (LLC-PK1)]. AB - The oxalate uptake was studied in LLC-PK1 cells, an epithelial cell line originated in proximal tubular cells of porcine kidney. It was clear that the cells contain an oxalate exchanger highly sensitive to 4,4-diisothio cyanostilbene-2-' disulfonic acid (DIDS). The uptake was inhibited by the addition of inorganic anions (chloride, sulphate and bicarbonate) to the reaction system, but was unaffected by sodium ion. The data suggest the possibility that it should be consistent with at least two transport systems for oxalate in LLC PK1 cells, a SO4-/oxalate/HCO3- exchanger and a Cl-/oxalate exchanger. PMID- 8345727 TI - [Clinical experience of simultaneous fiber-urethrocystoscopy and cystometry recording]. AB - We performed fiber-urethroscopy and cystometry recording simultaneously in 15 male patients. Fifteen patients were consisted of 12 complaining of micturition difficulty (such as BPH, NB, BNS) and 3 normal control. Fiberscope, Olympus CYF-1 and BF3C10, and cystometry were connected the DISA system. Firstly, we insert fiberscope from the urethra to bladder careful, and then cystometry recording using carbon dioxide gas started under direct vision of fiberscope. We compared cystometrical parameters based on our original method to these on conventional one. There were slight statistical significances in the pressure at the first desire to void and the maximum desire to void. But these differences as well as the frequently and the size of uninhibited contraction were not induced by the caliber of the urethroscopy. In conclusion, cystometric recording and urethroscopic observation using fiberscope are simultaneously carried out safely without reducing their diagnostic accuracy. PMID- 8345728 TI - [Investigation on recurrent and evolutionary factors in superficial bladder cancer]. AB - To evaluate clinical and pathological factors responsible for tumor recurrence, disease progression and upper urinary tract reoccurrence, we reviewed data from 244 patient with superficial bladder cancer (pTa and pT1) who were initially treated by bladder sparing operation between 1961 and 1990. The factors assessed in the present analysis included sex, age, interval between initial symptoms and first consultation, presence of hematuria, bladder irritability, tumor shape, tumor base configulation size, number, grade, stage, initial treatment, bladder instillation and medication. Accumulated recurrence rates were 13% for the first year, 20% for the second year, 23% for the third year and 28% for the fifth year. Tumor base configulation, number and grade demonstrated significant difference among each category. Multivariate analysis by the Cox's proportional hazards model confirmed that tumor number was the most important factor, followed by grade in this order. Disease progression developed in 7 patients (3%) and number and grade of tumor demonstrated significant difference. Progression was noted in 60% of multiple, G3 and pT1 tumor. Upper urinary tract recurrence developed in 5 patients (2%), however, we can find no risk factor for upper urinary tract recurrence. PMID- 8345729 TI - [Histopathological comparison of prostatic adenocarcinoma in Japan and the United States]. AB - Histopathological comparison of clinical prostatic adenocarcinoma between Japan and the United States (US) has been made with retrospective analyses on 1,037 and 987 cases, respectively. All cases were histologically evaluated by the same pathologist (M.H.) without previous knowledge of clinical information according to application of the Japanese General Rules for Prostatic Cancer (JGRPC) based on the predominant degree of histological differentiation, the nuclear grading by WHO classification and the Gleason grading systems. The age distribution of the patients was slightly different among both groups. However, this difference appeared not to be essential, because there existed difference of the date on diagnosis between two groups. Even though considering this time difference on registration, much more cases from Japan had stage D disease. The observed incidence of the histological differentiation classified by JGRPC among over-all cases did not show significant difference, however, the incidence among the cases with same stage between two groups differed with some statistical significance. Much more cases from the US fell in well differentiated adenocarcinoma and frequency of moderately differentiated adenocarcinoma was higher in the Japanese even in the cases diagnosed at advanced stages. The observed incidence of nuclear grade 3 was also higher in the Japanese. Gleason primary and secondary grade 5 and score 9-10 appeared more frequently in the cases from Japan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345730 TI - [Histopathological comparison of stage A prostatic adenocarcinoma in Japan and the United States]. AB - Histopathological characteristics of stage A prostatic adenocarcinoma from Japan (137 cases) and the United States (51 cases) were comparatively evaluated by retrospective analysis. All cases were examined by one referee pathologist (MH) using classification based on Japanese General Rules for Prostatic Cancer (JGRPC), nuclear grading by Mostofi-WHO system and Gleason grading. The incidences of the cases with well differentiated, low nuclear anaplasia and Gleason grade 1 or 2 on primary and secondary grades as well as histologic score 2-4 were much more higher in the cases from Japan as compared with those from the US. In the cases from the US proportion of the cases with moderately differentiated adenocarcinoma and grade 2 nuclear anaplasia exceeded those with well differentiated and grade 1 anaplasia. Adenocarcinomas with Gleason grade 3 in primary and secondary grade and 6-8 of histologic score were also more frequently observed in the cases from the US. No different distribution of each histologic grade could be obtained among the Japanese cases classified stage A2 and entire cases from the US. These results suggest that much more stage A adenocarcinoma in the US might fall into A2 if strict criteria was applied for subcalssification of stage A, which may reflected in the remarkable difference in the incidence of clinical prostatic carcinoma. PMID- 8345731 TI - [A case of cutaneous squamous cell carcinoma after renal allotransplantation]. AB - We describe herein a renal transplant recipient who developed cutaneous squamous cell carcinoma 15 years after the first transplantation. A 41-year-old Japanese man received a renal transplant from his mother for end-stage glomerulonephritis in December 1975 when he was 25 years old. Unfortunately, he suffered irreversible chronic rejection and returned to hemodialysis in March 1986. In December 1986 he received the second renal transplant from his father. In November 1990, the patient developed a nodule just lateral to his right lateral eye angle. He was treated with cryosurgery by a nearby dermatologist four times. However, the lesion did not improve, and he came to our hospital. Cutaneous biopsy specimen showed squamous cell carcinoma. The nodule was resected without decreasing the dose of cyclosporine and azathioprine. He has remained asymptomatic with out evidence of recurrent cutaneous lesions for two years of followup. This patient seems to represent the 3rd case of cutaneous cancer after renal transplantation in Japan. PMID- 8345732 TI - [Renin-secreting renal tumor. A case report]. AB - We reported a case of juxtaglomerular cell tumor, which excessively produced renin, resulting in secondary hypertension. A 25-year-old woman complained of headache and nausea. Hypertension and elevation of plasma renin activity were found by physical and laboratory examination. US and CT showed a space occupying lesion at upper pole of the right kidney. Angiography showed a hypovascular area at the corresponding area of the right kidney. Renin-secreting renal tumor of the right kidney was diagnosed and right nephrectomy was performed. Postoperatively, blood pressure and plasma renin activity became normalized and symptoms ameliorated. The juxtaglomerular cell tumor was pathologically confirmed and localization renin in the tumor cells was shown by immunohistochemical study. Forty one cases of juxtaglomerular cell tumor have been reported, since Robertson reported the first case. We discussed the clinical and pathological characteristics of the disease in this report. PMID- 8345733 TI - [AIDS]. PMID- 8345734 TI - [Renal functions of the patients with long-term catheterization in upper urinary tract]. AB - In order to investigate long-term effects of indwelling urinary catheters on renal functions, in 46 patients (27 male and 19 female) with ureterostomy or nephrostomy serum creatinine values were measured periodically. Average age of the patients was 60.6 years old. Duration of catheterization was more than 3 years (average 8.1 years). Renal dysfunction was defined as an elevation of serum creatinine more than 2 mg/dl. It was found that catheterization used more than 15 years evoked renal insufficiency over 50% of such patients. This period, however, was shorten to 11 years in patients with nephrolithiasis or frequent fever. It was concluded that urolithiasis and symptomatic urinary tract infections were two remarkable risk factors for the deterioration of renal functions, and that these risk factors must be avoided in patients on long-term catheterization in the upper urinary tract. PMID- 8345735 TI - Quality of life. PMID- 8345736 TI - Wellness and aging: are nurses ready for the year 2000? PMID- 8345737 TI - Perspectives on gerontologic nursing. PMID- 8345738 TI - Cognitive control: a concept worth considering for older adult clients. PMID- 8345739 TI - Our future in history. PMID- 8345740 TI - LPN's and i.v.'s. Questions & answers. PMID- 8345741 TI - [How does reflexology enrich nursing care? 2. A reflexologic follow-up in intensive care service]. PMID- 8345742 TI - [Continuing education and the future of the profession. What do we expect of specialists?]. PMID- 8345743 TI - [The role of the nurse anesthetist. "Let us use nursing procedures"]. PMID- 8345745 TI - [The onerous heritage of serving and caring...]. PMID- 8345744 TI - ["Education new--career free", a congress report. Start towards new horizons]. PMID- 8345746 TI - [Education, so everybody becomes a winner]. PMID- 8345748 TI - [When practice and school cooperate: education, responsive to new nursing requirements]. PMID- 8345747 TI - [The profession at the threshold of the university. The door has been unlocked]. PMID- 8345750 TI - [Petition launched]. PMID- 8345751 TI - [Specialization--mode or necessity?]. PMID- 8345749 TI - [All that is different in the health professions]. PMID- 8345752 TI - [Nuclear weapons and the law. The medical society must take its responsibility]. PMID- 8345753 TI - [Clarifications concerning hospices]. PMID- 8345754 TI - [Misunderstanding psychodynamics]. PMID- 8345755 TI - [Cooperating clinics--pathology departments are important]. PMID- 8345756 TI - [Guidelines in the book on proctology are well-founded]. PMID- 8345757 TI - [Do we physicians want to be graded?]. PMID- 8345758 TI - [It is incorrect to measure only the number of patient admissions]. PMID- 8345759 TI - [Protect the vaccines]. PMID- 8345760 TI - [To compare the quality between different clinics is difficult]. PMID- 8345761 TI - [Eye examination in diabetes. Every year or every other year?]. PMID- 8345762 TI - [Nitric oxide. A new drug in lung disease?]. PMID- 8345763 TI - [Magnetic resonance tomography. A new method in the diagnosis of breast cancer]. PMID- 8345764 TI - [Primary breast reconstruction. An alternative to breast-conserving surgery]. PMID- 8345765 TI - [Acupuncture therapy in stroke. Patients experience significant improvement]. PMID- 8345766 TI - [Rehabilitation after stroke. The plasticity of the brain is an unexplored resource]. PMID- 8345767 TI - [Epidemiology of infections in primary health care. It is needed but who is going to pay for it?]. PMID- 8345768 TI - [Cutaneous malignant melanoma. Perform excisions of pigmented changes on wide indications]. PMID- 8345769 TI - [Do not normalize drug addiction. Resignation is not a solution of the drug problem]. PMID- 8345770 TI - [The economical incentives change health care. First year of the Stockholm model]. PMID- 8345771 TI - Effects of alterations in auditory feedback and speech rate on stuttering frequency. AB - This study investigated the effects of altered auditory feedback on stuttering frequency during speech production at two different speech rates, Nine stutterers, who exhibited at least 5% dysfluency during a reading task, served as subjects. They read eight different passages (each 300 syllables in length) while receiving four conditions of auditory feedback: nonaltered, masking, delayed, and frequency altered. For each auditory feedback condition, subjects read at both a normal and a fast rate. Results indicated that stuttering frequency was significantly decreased during conditions of delayed and frequency altered auditory feedback at both speech rates (p < 0.05). These findings refute the notion that a slowed speech rate is necessary for fluency enhancement under conditions of altered auditory feedback. Considering previous research and the results of this study, it is proposed that there may be two interdependent factors that are responsible for fluency enhancement: alteration of auditory feedback and modification of speech production. PMID- 8345772 TI - Productions of English vowels by native speakers of Arabic: acoustic measurements and accentedness ratings. AB - Productions of ten English vowels in /bVt/ and /bVd/ contexts were elicited from a group of native American English speakers and a group of native Arabic speakers who had learned English in adulthood. When a variety of acoustic measurements, including vowel durations, F1 and F2 frequencies, and movement in F1 and F2 were examined, the two groups were found to differ on at least one of these parameters for nearly every vowel considered. A subset of the Arabic speakers' productions, and the productions of two native English speakers, were rated for accentedness by five native English judges. The rating data indicated that only a minority of the Arabic group's productions were regarded by the judges as "native-like". When the acoustic measurement data were regressed on the mean ratings, it was found that the accentedness scores were correlated primarily with F1 frequency and movement in F2, although the significant predictors varied from vowel to vowel. PMID- 8345773 TI - Progressive utterance-final lengthening in syllables with final fricatives. AB - The generality of the pattern of progressively greater lengthening within the utterance-final syllable, previously found with respect to final stops, is shown to extend to syllables in Hebrew with final fricatives. Seven native speakers of Hebrew read matched sentence pairs in which bisyllabic key words appeared in non final and sentence-final position. Final fricatives showed almost four times as much utterance-final lengthening as the preceding stressed vowel. Final lengthening affected the duration of each segment of the final syllable, and also extended to the initial unstressed syllable of the final word. Though final fricatives showed more lengthening in sentence-final position than final-stop closures, no difference was found in the lengthening of the vowels preceding these consonants. The greater lengthening of the final fricative relative to the preceding vowel resulted in C/V ratios which failed to distinguish between the voiceless fricative in non-final position and the voiced fricative in utterance final position. These results suggest that sentence position is taken into account in the perception of voicing, such that the C/V ratio applicable in non final position is increased by a factor of two in final position. PMID- 8345774 TI - PREVIEW: a new ultrafast imaging sequence requiring minimal gradient switching. AB - A new ultrafast imaging technique is presented that can be performed on standard, unmodified magnetic resonance imaging spectrometers. The method uses very few gradient switching steps and does not require that the switches are very rapid. It is based on the generation of a multiplicity of signals by a few radiofrequency (RF) pulses and their separate frequency- and phase-encoding before acquisition of all signals in a single period. PMID- 8345775 TI - Differentiation of benign from malignant breast masses by time-intensity evaluation of contrast enhanced MRI. AB - Using gadolinium-DTPA enhanced MRI we analyzed the enhancement characteristics of palpable breast masses in 23 patients--10 cancers and 13 benign lesions. The most specific finding for separating benign from malignant lesions was a ratio of maximum intensity change divided by the time interval during which this first occurred. Designated ranges of this ratio were specific for benign disease and sensitive for malignancy in this small patient group. Three of eight fibroadenomas exhibited enhancement patterns indistinguishable from cancer. PMID- 8345776 TI - High resolution spin-echo imaging of the temporomandibular joint. AB - High resolution thin section (1.5 mm thick) spin echo images (HRSE) with narrow bandwidth of TMJ were compared to the conventional (3 mm thick) spin echo images (CSE) in 20 symptomatic patients. Our results revealed that the disk delineation was superior with HRSE and the degree of confidence in making the diagnosis was significantly higher with HRSE than with CSE. Narrow bandwidth, high resolution spin echo technique offers better anatomic detail in the TMJ, resulting in improved degree of confidence, without penalty in additional imaging time. PMID- 8345777 TI - Echo-planar chemical shift imaging of silicone gel prostheses. AB - We have developed an echo-planar (EP) proton chemical shift imaging (CSI) MR technique that allow us to discriminate the polydimethylsiloxane (PDMS, silicone) proton MR signal from that of the fat and water protons found in tissues, in order to map the distribution of PDMA in humans who have silicone gel prostheses. Silicone gel-filled prosthetic implants induce histologic changes in the surrounding tissue which are attributed to the leakage of free PDMS from the prosthesis. The T2 relaxation measurements of three silicone gels show that there are two components in them, each with a different degree of molecular mobility. The presence of free silicone is confirmed by chloroform extraction, which removed 14-28% of the material. This free polymer present in the gel can pass through the intact or ruptured membrane of the implant into the surrounding tissue. Our preliminary imaging results indicate that EP-CSI MR might be useful as a diagnostic technique for implant malfunction. PMID- 8345778 TI - Mechanisms that contribute to the in vitro relaxation and signal intensity of water in barium sulfate suspensions used as MRI contrast agents. AB - The individual components of two commercially available barium sulfate (BaSO4) suspensions, Liquid HD and E-Z-paque (E-Z-EM Inc., Westbury, NY), were investigated to determine their contribution to relaxation. Longitudinal and transverse relaxation times of suspensions and solutions of the different BaSO4 particles and the vehicle used to keep them in suspension were measured separately at 2.0 T. A multiple echo Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was used for T2 determinations with different values of the echo spacing 2 tau. Longer values of 2 tau resulted in significant shortening of the calculated T2 relaxation times, indicating that the major mechanism leading to signal loss in BaSO4 suspensions is the diffusion of water molecules through susceptibility gradients in the vicinity of suspended particles. At higher BaSO4 concentrations, decreased water proton density also produces significant signal loss. Viscosity has little effect on the relaxation. A combination of larger and smaller BaSO4 particle sizes was found to be more effective than smaller sizes only in enhancing signal decay. PMID- 8345779 TI - Dual contrast enhancement of both T1- and T2-weighted sequences using ultrasmall superparamagnetic iron oxide. AB - BMS 180549 (previously AMI-227), an ultrasmall superparamagnetic iron particulate agent, was investigated to determine its utility as a contrast agent on T1 weighted, as well as T2-weighted sequences, as a function of route of administration, (intravenous versus selective arterial) and concentration. Twelve farm pigs were divided into three groups of four each by route of administration (intravenous, selective superior mesenteric, or selective hepatic arterial injection). 10 mumol/kg and 20 mumol/kg dosages were given and evaluated both immediately after and 20-24 hr after contrast infusion, using both spin-echo and gradient-echo T1 and T2-weighted sequences. Significant postcontrast liver and spleen enhancement was noted at both concentrations, regardless of route of administration on both T1- and T2-weighted sequences. The earliest postcontrast T1-weighted sequence obtained during the 1-3 min interval following IV administration of high dose (20 mumol/kg) contrast demonstrated an average of +42.8% liver and +249.0% spleen enhancement; 24 hr later this decreased to 0 and 7.2%, respectively. The earliest postcontrast T2-weighted sequence obtained during the 8-17 min interval post high-dose IV contrast showed an average of 75.8% decrease in liver and -28.7% decrease in spleen signal intensity; 24 hr later the magnitude of these changes diminished to -33.1% and +2.5%, respectively. No significant difference was noted in liver or spleen enhancement, regardless of route of contrast administration (intravenous versus intraarterial). PMID- 8345780 TI - NMR-contrast enhancement of experimental brain tumors with MnTPPS: qualitative evaluation by in vivo relaxometry. AB - The applicability of the synthetic manganese porphyrin MnTPPS as tumor-selective MRI-contrast agent for brain tumors was investigated quantitatively by in vivo relaxometry. To exclude toxic effects of side products, the purification method for MnTPPS was improved. As a result, MnTPPS+Cl- (free acid) with a purity of more than 99.8% was obtained. For the in vivo quantification of the contrast effect the magnetization M(0) and the transversal relaxation time T2 were evaluated in different regions of rat brains with or without implanted gliomas and in temporal muscle. Measurements were performed before and after the application of MnTPPS. The ratio of the magnetization M(0) (TR = 3.5 sec) of the tissue under investigation and the contralateral striatum was defined as contrast ratio Rc(0). Without MnTPPS Rc(0) of edema (0.93 +/- 0.08) and tumor (0.91 +/- 0.07) did not differ from normal brain tissue (corpus callosum: 0.96 +/- 0.07; cortex: 0.98 +/- 0.05). T2 of edema (110 +/- 12 msec) and intracranial tumor (93 +/- 7 msec) were significantly longer than in normal tissue (corpus callosum: 73 +/- 8 msec; parietal cortex: 75 +/- 6 msec; striate nucleus: 78 +/- 7 msec, p < .01). Two hours after the injection of MnTPPS, magnetization of neoplastic tissue was selectively enhanced (TR = 3.5 sec), and T2 was reduced. The smallest dose of 0.06 mmol/kg body weight (bw) increased Rc(0) to 1.12 +/- 0.04, and 0.38 mmol/kg to 1.30 +/- 0.13 (p < .01). T2 of tumor decreased to 85 +/- 6 msec after 0.06 mmol/kg and to 65 +/- 6 msec after 0.38 mmol/kg bw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345781 TI - Comparison between Gd-DTPA, Gd-EOB-DTPA, and Mn-DPDP in induced HCC in rats: a correlation study of MR imaging, microangiography, and histology. AB - The behaviour of two liver-specific contrast MR agents, Gd-EOB-DTPA and Mn-DPDP and one nonspecific contrast agent, Gd-DTPA, was compared in a rat model of chemically induced hepatocellular carcinoma (HCC). The study included contrast enhanced MR imaging and the corresponding microangiography and histology. Analysis of the MR images showed similar degrees of maximum relative liver enhancement: 47.5 +/- 8.2% for Gd-EOB-DTPA (0.03 mmol/kg) at 5 min postinjection and 52.5 +/- 14.4% for Mn-DPDP (0.025 mmol/kg) at 15 min; both exceeded the value obtained with Gd-DTPA (34.8 +/- 13.6%, at 5 min), even at 0.3 mmol/kg. Gd-EOB DTPA caused a similar "negative" enhancement of all types of HCC, independent of their differentiation and vascularization, i.e., lesion-to-liver contrast-to noise ratio (CNR) of differentiated and undifferentiated HCC increased negatively from, respectively, 1.9 +/- 1.1 and -5.1 +/- 3.1 before contrast to -5.2 +/- 2.4 and -11.8 +/- 4.8 at 5 min after contrast. On Mn-DPDP enhanced images, the undifferentiated HCCs showed up negatively (CNR -5.5 +/- 4.7 before contrast to 13.7 +/- 10 at 15 min after contrast), whereas the more differentiated tumors showed up positively (CNR from 2.3 +/- 2.0 before contrast to 12.5 +/- 3.5 at 24 hr postcontrast) due to active uptake and delayed elimination of Mn-DPDP. PMID- 8345782 TI - Complementary use of T2- and postcontrast T1-weighted NMR images for the sequential monitoring of focal ischemic lesions in the rat brain. AB - The noninvasive nature of NMR imaging enables serial studies on a single animal. In 12 male Wistar rats, the dynamic progression of a photochemically induced (Rose Bengal) infarct was studied starting immediately after induction and up to 10 days. The results demonstrated that both T2- and postcontrast T1-weighted NMR images are required to discern the time dependent dynamics of the ischemic process. The ischemic lesion was already visible on T2-weighted images within 30 min after the induction. Twenty-four hours after the insult, both area and intensity reached maximum values. Hereafter and up to day 10, both parameters decreased. Postcontrast T1- weighted images revealed a blood-brain barrier (BBB) rupture immediately after the induction which persisted until 10 days after the insult. The application of contrast agents such as Gd-DOTA or Gd-HP-DO3A also allowed the detection of 10-day-old lesions which were not always discernable on T2-weighted images. The penetration of both contrast agents in the affected area proceeded slower the first 5 days after the insult while at day 10, maximum contrast enhancement was reached almost immediately after administration of the contrast agent. At 24 hr after the insult, the discrepancy between the lesion area as determined on T2-weighted images and on postcontrast T1-weighted images was maximal. At this stage, the lesion was characterized by central core with a leaky BBB surrounded by a reversible zone which appeared enhanced on T2-weighted images. PMID- 8345783 TI - Baseline consideration of liposomal contrast agent. CNS transport by macrophages in experimental allergic encephalomyelitis. AB - The purpose of this study was to investigate a specialized liposomal contrast agent for magnetic resonance imaging (MRI), as part of a program to examine infiltrating immune cells in lesions of experimental allergic encephalomyelitis (EAE). A potent investigational liposomal contrast agent, phosphatidylethanolamine-DTPA-gadolinium, was chosen which has been shown to remain tightly liposomal-associated, with long persistence in vivo. Europium (Eu3+), a fluorescent paramagnetic metal, was also utilized in these experiments in place of gadolinium. This material is avidly taken up by monocytes in vivo. Thirty-four animals received some form of liposomal material either before or during the opening of the blood-brain barrier (BBB). Twenty-seven Hartley guinea pigs were inoculated for EAE with homogenized brain and Complete Freunds Adjuvant (CFA) and seven control animals received CFA alone. Eighty-two percent of the experimental animals exhibited degeneration of the BBB with inflammation and edema in the brain, while all control animals had normal brain scans. T1-weighted MRI, performed to detect the presence of liposomal contrast material in experimental animals, was not different from untreated animals. Fluorescent microscopy revealed no characteristic changes associated with Eu3+ presence in the brains of treated or control animals. Therefore, it would seem that insufficient material crosses the disrupted BBB, either in free form or subsequent to macrophage ingestion, to be detected by MRI or fluorescent microscopic examination. PMID- 8345784 TI - Uptake and life time of fluoride ion in rats by 19F-NMR. AB - 19F nuclear magnetic resonance (NMR) was utilized to obtain information on the uptake and half-life time of fluoride ion in rats. Changes in tissue fluoride level after acute loading were monitored over time in blood and tissue homogenates obtained from liver and brain. The rate of fluoride elimination from various tissues was roughly similar, following in all cases a first-order kinetic rate law. The F- concentration in brain was about 20% of that found in liver, indicating a reduced fluoride diffusion across the blood-brain barrier. In vivo F spectra were obtained in rat brain in few minutes with a good signal-to-noise ratio; this confirms the possibility of extending the use of F- as a probe of biomolecules to in vivo applications. PMID- 8345786 TI - The use of agarose gels for quantitative determination of fluid saturations in porous media. AB - The use of agarose gel reference standards for quantifying petrophysical properties in porous media is described. The specific interest is to determine the values of fluid saturations and porosity in oil bearing rocks; the MRI methodology for estimating these properties is discussed. It is shown that the relaxation times of the gel reference standard and the relaxation times of the fluid contained in the porous media affect the estimation process. The determination of porosity and fluid saturations can be greatly simplified if the relaxation times of the reference standard and the relaxation times of the fluid are closely matched. Gel concentration of paramagnetic impurities in the form of copper ions is used to control the longitudinal relaxation properties. The relaxation properties of agarose gels, as a function of agarose and paramagnetic impurity concentrations, have been measured at 2.0 T. The data are well fitted by a simple polynomial in agarose concentration and paramagnetic impurity concentration. Finally, a one-dimensional imaging example of use of agarose gels as reference phantoms is discussed. PMID- 8345785 TI - Use of transmission line analysis for multi-tuning of birdcage resonators. AB - A general analysis for double- and higher order tuning of birdcage resonators is presented based on a lumped element transmission line model. Expressions were developed for the determination of the resonant frequencies of bandstop and bandpass birdcage coils and, with specific restrictions, for capacitor values required to obtain any two desired mode one resonant frequencies. Experimental measurements on three variants each of an eight-column bandstop and an eight column bandpass were in excellent agreement with theory; the average absolute frequency difference and percent deviation were 1.51 +/- 1.57 MHz and 2.61 +/- 2.36%, respectively. In addition, 31P and 1H phantom images were obtained at 2.0 T using a representative bandstop coil. PMID- 8345787 TI - MR image compression using iterated function systems. AB - This paper presents a method for MR image compression using iterated function systems based on fractal models. The method makes use of self-similarities of an image and achieves compression by matching similar image blocks. A fast matching procedure is proposed in this paper for efficient image encoding. The method is tested with real MR images. PMID- 8345788 TI - MRI and determination of T1 and T2 of solid polymers using a 1.5 T whole-body imager. AB - Spin-echo sequences with echo times as short as 3.5 msec were implemented on a standard 1.5 T NMR whole-body imager for 1H imaging of polymers in the solid state. No modification of the NMR hardware designed for clinical usage was made. Beside images of different polymers a "self-portrait" of the polymeric materials of the receiver coil is given as a neat application. Based on imaging experiments the longitudinal and transverse relaxation time of polymers were investigated. The results indicate that using a standard whole-body imager, it is possible to provide additional information to other examination techniques in polymer and materials science. PMID- 8345789 TI - A theoretical study of amplitude modulation and time shifting in quantitative MR measurements of motion in brain tissue. AB - MR imaging pulse sequences can be made sensitive to motion by adding gradients with different strengths at different time intervals. In the well-known phase mapping method, such velocity encoding gradients are used to obtain phase information linear to the velocity of the studied object in the direction of the gradient. When very low velocities are studied, a long duration velocity-encoded gradient is required to obtain sufficient velocity sensitivity. In such cases, variation in the object velocity during the execution of the sequence may hamper the accuracy of the method. In this study, we have made a computer simulation of the performance of a phase mapping method sequence (TE = 46 msec) designed for quantitative studies of motion in brain tissue. Using a Gaussian-shaped velocity input function, the time shifting and the amplitude modulation properties of the sequence was studied for various values of the duration, defined as the full width of tenth of maximum (FWTM), of the input function. The time shift corresponded well to the center of the 180 degrees RF pulse, and the amplitude modulation was seen to decrease with increasing time duration of the velocity input function. Applied on in vivo data, where an approximately gaussian-shaped brain motion velocity pattern was assumed to have a duration of 150 msec, the amplitude modulation of the sequence was estimated to 2%. PMID- 8345790 TI - Apolipoproteins A-I and B and cholesterol in synovial fluid of patients with rheumatoid arthritis. AB - Synovial fluid (SF) of patients with rheumatoid arthritis (RA) has been noted to contain cholesterol crystals and increased amounts of cholesterol compared with normal SF. SF, plasma apolipoproteins (apos) A-I and B, and cholesterol in 12 untreated classic RA patients (inflammatory arthritis) and eight untreated degenerative joint disease ([DJD] noninflammatory arthritis) patients were analyzed. Results showed that mean apo A-I, apo B, and cholesterol levels of RA SF were significantly higher than those of DJD SF (apo A-I, P = .004; apo B, P = .0008; cholesterol, P = .0004). Regression analyses of plasma and SF apo A-I and apo B (r = .72, P = .008 and r = .63, P = .02, respectively) suggested an increased permeability for these lipoprotein constituents across RA synovial membrane that was not observed in DJD synovial membrane. These data suggest that RA synovium but not DJD synovium is more permeable to major apoproteins of low- and high-density lipoproteins (LDL and HDL). These apolipoproteins have been shown to influence the immune response and may therefore be involved in the pathogenesis of RA. PMID- 8345791 TI - Lipoprotein-X fails to inhibit hydroxymethylglutaryl coenzyme A reductase in HepG2 cells. AB - Abnormalities of lipid composition and metabolism are frequently observed in patients with cholestatic liver disease. Both elevated low-density lipoprotein (LDL) levels and the appearance of lipoprotein-X (LP-X) in plasma underlie the high incidence of hypercholesterolemia in this population. We tested the hypothesis that the hypercholesterolemia of cholestasis may reflect a failure of normal feedback regulation of hepatic cholesterogenesis by determining the influence of LP-X on the rate-limiting enzyme of cholesterol synthesis, hydroxymethylglutaryl coenzyme A (HMG CoA) reductase. Cultured human hepatoma (HepG2) cells were incubated in purified lipoprotein for 24 hours, harvested, and then assayed for HMG CoA reductase activity and mass. LDL isolated from either normal controls or patients with cholestasis decreased reductase activity in a dose-dependent fashion (2 to 30 micrograms cholesterol/mL media) to a level approximately 50% of that measured in cells incubated in lipid-deficient serum. LP-X failed to downregulate enzyme activity compared with LDL, with little change in reductase activity at cholesterol concentrations (30 micrograms/mL media) that produced maximal reductase inhibition by LDL. Three distinct LP-X subspecies were purified from the plasma of a patient with primary biliary cirrhosis (PBC) and tested in an analogous manner. All LP-X subspecies were similar in their inability to decrease reductase activity as compared with LDL. HMG CoA reductase mass was increased approximately twofold in cells incubated with LP-X, as estimated by Western blot analysis. These results suggest that LP-X may contribute to hypercholesterolemia in the cholestatic patient by not effectively downregulating hepatic cholesterol synthesis. PMID- 8345792 TI - Factors influencing excess postexercise oxygen consumption in trained and untrained women. AB - This study investigated the effects of blood lactate and norepinephrine levels and rectal temperature on excess postexercise oxygen consumption (EPOC) following two different exercise intensities. Six trained and seven untrained women each performed two exercise tests, short-term high-intensity exercise ([HI] approximately 80% maximum oxygen consumption [VO2max]) and long-term low intensity exercise ([LOW] approximately 65% VO2max) until 300 kcal were expended. Rectal temperature, oxygen consumption (VO2), and lactate and norepinephrine levels were monitored at rest, during exercise, and for 60 minutes into recovery. Exercise times averaged 30.0 +/- 4.5 and 23.7 +/- 0.9 minutes in trained women and 45 +/- 3.6 and 30.0 +/- 0.4 minutes in untrained women for LOW and HI, respectively. Rectal temperature, VO2, and lactate and norepinephrine levels were significantly elevated (P < .05) during HI compared with LOW in both groups. VO2 was elevated throughout recovery following LOW and HI in untrained women only. Additionally, VO2 was elevated until minutes 50 and 40 following LOW and HI, respectively, in trained subjects. Rectal temperature returned to resting levels after 30 minutes of recovery following LOW, but remained significantly elevated throughout minute 50 of recovery following HI in trained women. However, values remained significantly elevated throughout recovery following both exercise bouts in untrained subjects. Norepinephrine levels remained elevated above resting levels throughout recovery following HI and until minute 50 following LOW in trained subjects, whereas levels remained elevated for 5 minutes following LOW and 50 minutes following HI in untrained subjects. Lactate levels remained elevated above baseline values throughout recovery following HI and LOW in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345793 TI - Quantitative evaluation of the effect of low-intensity exercise on insulin secretion in man. AB - We studied insulin secretion rates (ISR) during low-intensity exercise (40% peak aerobic capacity [VO2]) in 12 normal subjects to assess the contribution of altered insulin secretion to the reduction in peripheral insulin concentrations associated with exercise. ISR were calculated by a previously validated method of two-compartment analysis of peripheral C-peptide concentrations using individual parameters derived following a bolus injection of biosynthetic human C-peptide. In addition, the effect of low-intensity exercise on kinetic parameters of C peptide was evaluated. The results showed that low-intensity exercise did not significantly affect C-peptide kinetics. Peripheral insulin concentrations and ISR decreased to a similar degree throughout exercise. There was a mean maximum decrease in serum insulin concentrations from 42 +/- 5.4 pmol/L basally to 24 +/- 2.6 pmol/L, constituting a 51% +/- 5.9% decrease (P < .001), and ISR decreased from 85.7 +/- 11.9 pmol/min to a nadir of 45.6 +/- 10.6 pmol/min (P < .001), a 48% +/- 8.4% decline. Plasma glucose and glucagon concentrations did not change significantly either during or after exercise, although there was a matched twofold increase in glucose utilization and disposal rates. We suggest that the reduction in peripheral insulin concentrations during exercise is due to reduced insulin secretion. PMID- 8345794 TI - Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy. AB - Estrogen/progestin steroid combinations adversely affect glucose tolerance and insulin resistance, but their effects in combined hormone replacement therapy (HRT) have rarely been evaluated. We studied 61 untreated symptomatic postmenopausal women randomized to receive oral (conjugated equine estrogens, 0.625 mg/d continuous + levonorgestrel, 0.075 mg/d for 12 days of each 28-day cycle) or transdermal therapy (estradiol 17 beta, 0.05 mg/d continuous + norethindrone acetate, 0.25 mg/d for 14 days of each 28-day cycle). An untreated control group of 30 postmenopausal women not seeking HRT was also studied. Intravenous glucose tolerance tests (IVGTT) were performed at baseline and 3, 6, and 18 months later. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. There were no changes in glucose or insulin concentrations with transdermal therapy. Oral therapy caused a deterioration of glucose tolerance and an increased overall plasma insulin response, apparently due to a reduction in the immediate plasma insulin response to glucose. This may have resulted from increased hepatic insulin uptake, uncompensated for by an increase in first-phase pancreatic insulin secretion. Neither treatment caused significant insulin resistance compared with baseline, but with the oral treatment insulin resistance was greater during the combined phase compared with the estrogen-only phase. Thus the oral regimen affected both insulin delivery and insulin resistance. The transdermal regimen had relatively few effects on insulin metabolism. PMID- 8345795 TI - Pancreatic beta-cell destruction in non-obese diabetic mice. AB - We determined the natural history of the widespread pancreatic islet beta-cell destruction that precedes the onset of spontaneous putative autoimmune diabetes mellitus in NOD mice. For this purpose, we performed both histological and immunocytochemical examinations of pancreata retrieved from mice at 2 through 30 weeks of age. An overexpression of la antigens was identified on islet beta cells at 4 weeks of age, without evidence of mononuclear cell infiltration. The abnormal expression of la antigens was age-related and was associated with hyperexpression of class I antigens and progressive islet cell histologic damage after 17 weeks of age. Immunocytochemical examination of islet cell infiltrate showed that the number of macrophages did not increase during the early phase of islet cell damage in these mice. The L3T4/Lyt-2 ratio increased after 7 weeks of age, but was 1:1 in the late stage of insulitis. These findings suggest that widespread islet beta-cell destruction is a process that begins primarily with derangements of the pancreatic beta-cell immune pattern, which may trigger a mononuclear cell reaction. PMID- 8345796 TI - An evaluation of fetal glucogenesis in intrauterine growth-retarded pregnancies. AB - The presence of fetal glucogenesis was evaluated in nine patients with pregnancies complicated by intrauterine growth retardation (IUGR) at the time of fetal blood sampling (FBS) between 29 and 35 weeks of pregnancy. Eight were singleton pregnancies and one was a twin pregnancy in which blood samples were obtained from both twins. A maternal primed-constant infusion of D(U-13C]glucose was performed, and the presence of fetal glucogenesis was assessed by a comparison of steady-state maternal and fetal glucose enrichments. No significant difference was present between maternal and fetal molar percent excess ([MPE] P = .97), and the mean fetal to maternal (F/M) MPE ratio (0.99 +/- 0.01) was not significantly different from 1 (P = .76). F/M MPE ratio was independent of the time of FBS and umbilical venous glucose and lactate concentrations. Thus fetal glucogenesis is not demonstrable in a group of fairly severe growth-retarded fetuses after an overnight fast with this relatively noninvasive approach. PMID- 8345797 TI - Cyclophosphamide-induced diabetes in Long-Evans Tokushima Lean rats: influence of ovariectomy on the development of diabetes. AB - We studied the effect of treatment with cyclophosphamide (CY) on the incidence of diabetes in Long-Evans Tokushima Lean (LETL) rats, a newly established strain of spontaneously type I diabetic rats. The overall incidence of diabetes among 356 LETL rats treated with CY was 25.6%, which was significantly higher than the 10.5% among 857 untreated LETL rats at 27 weeks of age, and there was no significant sex difference. The incidence of CY-induced diabetes in adult (> 16 weeks of age) female LETL rats was 7.7% (10/130), which was significantly lower than that in other CY-treated groups of LETL rats. No diabetes mellitus was induced by administration of CY to 23 diabetes-resistant LETO rats. There were no significant differences in the degrees of hyperglycemia or hyperketonemia in spontaneously and CY-induced diabetic LETL rats, but the plasma glycated albumin level of CY-induced diabetic rats (10.3% +/- 2.1%) was significantly higher than that of spontaneously diabetic rats (8.2% +/- 1.3%), suggesting that plasma glucose levels increased more rapidly in the latter. More than half of the diabetic rats showed type C or D morphological changes of the islets, ie, atrophic change with little mononuclear cell infiltration or almost complete loss of the islets. However, distributions of various types of morphological changes in the islets were not significantly different in the two groups. Ovariectomy (OVX) significantly increased the incidence of CY-induced diabetes in adult female rats from 7.7% to 20.8%. The number of CD8+ cells was significantly increased in noncastrated adult female LETL rats and decreased to the level of other groups after OVX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345798 TI - Is alcohol an osteoporosis-inducing agent for young and middle-aged women? AB - The effects of alcohol abuse on the bone of women have scarcely been investigated, although women are more prone than men to osteoporosis. We studied 19 noncirrhotic female alcoholics (aged 24 to 48 years) hospitalized for 2 weeks for withdrawal and three groups of control women (n = 182). Sixteen patients and all control subjects had regular menstrual cycles. Forearm bone mineral content (BMC) and axial bone mineral density (BMD) were measured by single-photon absorptiometry and dual-energy x-ray absorptiometry, respectively. Parameters of bone metabolism were analyzed at the beginning and end of the withdrawal period. BMC and BMD did not differ between patients and controls at any of the five measurement sites. On admission, bone formation of the alcoholics was depressed as reflected by osteocalcin levels (-48%, P < .01); it normalized during abstention (P < .01). Urinary hydroxyproline, a parameter of bone resorption, and serum intact parathyroid hormone were at the control level throughout the observation period. Serum ionized calcium level increased by 4% (P < .0001), and serum free fatty acid (FFA) levels decreased by 30% (P < .05) during withdrawal; there was an inverse correlation between changes in these two parameters (r = .49, P < .05). On admission, serum concentrations of 25-hydroxyvitamin D3 [25-OH D3] and 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3] were reduced by 46% (P < .001) and 16% (P = .16); these did not normalize during abstention. In conclusion, provided that liver cirrhosis and gonadal dysfunction are not contributing, even heavy drinking does not seem to decrease bone mass in young and middle-aged women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345799 TI - Three-year treatment of familial heterozygous hypercholesterolemia by extracorporeal low-density lipoprotein immunoadsorption with polyclonal apolipoprotein B antibodies. AB - Familial hypercholesterolemia is a disorder of lipid metabolism associated with a highly increased risk for cardiovascular disease. Since in such patients even combined drug therapy often fails to decrease low-density lipoprotein (LDL) cholesterol levels sufficiently, extracorporeal LDL elimination has been developed. We treated eight adult patients with LDL immunoadsorption using antibodies against apolipoprotein B without additional lipid-lowering drug therapy for 3 years; this procedure was performed at weekly intervals. By one treatment session, LDL cholesterol and lipoprotein(a) levels were decreased by 55%. Under regular treatment, mean LDL cholesterol levels of 165 mg/dL between two consecutive treatment sessions could be reached, compared with 522 +/- 24 mg/dL before any treatment. As high-density lipoprotein (HDL) cholesterol levels increased under regular treatment, the LDL/HDL cholesterol ratio decreased from 13.4 to 3.4. Positive influences on plasma and whole-blood viscosity as well as on erythrocyte aggregation also seem to be beneficial with regard to retarding atherosclerosis. Very-low-density lipoprotein (VLDL) levels were reduced by approximately 50% after treatment, accompanied by a marked increase of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activity. The effects of LDL apheresis on hemostasis, complement activation transport proteins, and hematological parameters were found to be small. In addition, no side effects amounting to any major clinical relevance occurred in any of the patients. After 3 years of LDL apheresis, a decrease in the frequency of anginal chest pain and ST segment depression on exercise testing and a marked reduction of tendon xanthoma size were observed. PMID- 8345800 TI - The response to lovastatin treatment in patients with heterozygous familial hypercholesterolemia is modulated by apolipoprotein E polymorphism. AB - In a retrospective study, we examined the influence of apolipoprotein (apo) E polymorphism and gender on the response to treatment with 80 mg/d lovastatin in a homogeneous population of patients with familial hypercholesterolemia (FH), most of whom were carriers of the 10-kb deletion of the low-density lipoprotein (LDL) receptor gene. Apo E phenotype distribution among the 189 FH patients was not different from that of a normal population sample. The total and LDL cholesterol (LDL-C) response to lovastatin in the overall group (men and women) was significantly lower in the E4 subset compared with E2 and E3 subsets. This finding is in agreement with trends observed in previous reports. On the other hand, the response of LDL-C to lovastatin was significantly lower in E4 men than in E4 women, whereas the high-density lipoprotein cholesterol (HDL-C) concentration in the E4 group increased significantly more in men than in women, suggesting a role of gender in modulating the response to lovastatin. Hence, apo E polymorphism influenced LDL-C (and HDL-C) response to lovastatin in men, but not in women, revealing the existence of a gene-by-gender interaction. These findings were independent of the nature of the LDL receptor defect. We conclude that male FH patients carrying the epsilon 4 allele respond less efficiently to lovastatin than men carrying the epsilon 3 or epsilon 2 allele or women of any apo E phenotype with respect to decreasing total cholesterol and LDL-C levels, but respond more efficiently with respect to increasing HDL-C levels. The full practical implication of these findings remains to be explored. PMID- 8345801 TI - Anticonvulsant-induced changes in tissue manganese, zinc, copper, and iron concentrations in Wistar rats. AB - Human epileptics have been reported to have low blood manganese (Mn) concentrations in comparison to nonepileptics, an observation that is important because Mn deficiency can increase seizure susceptibility in experimental animals. Factors that have been suggested to contribute to the low blood Mn levels in epileptics include anticonvulsant use, seizure-induced tissue redistribution of Mn, and genetics; in the present study, the first of these possibilities was tested. Wistar rats were fed semipurified diets containing diphenylhydantoin ([DPH] 3 g/kg diet), phenobarbital ([PB] 2 g/kg diet), or primidone ([PRIM] 3 g/kg diet) for 7 weeks, at which time they were killed and tissues collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations. In comparison to pair-fed rats, DPH- and PRIM-fed rats had significantly elevated liver Mn concentrations, while Mn concentrations in blood, brain, heart, and kidney were unaffected by anticonvulsant exposure. Changes in the concentrations of Zn, Cu, and Fe in specific tissues were also found. Overall, these findings suggest that the anticonvulsants tested do not lead to significant derangements in the metabolism of Mn. PMID- 8345802 TI - Comment on the recent studies of dietary fatty acid. PMID- 8345803 TI - Time course of the response of myofibrillar and sarcoplasmic protein metabolism to unweighting of the soleus muscle. AB - Contributions of altered in vivo protein synthesis and degradation to unweighting atrophy of the soleus muscle in tail-suspended young female rats were analyzed daily for up to 6 days. Specific changes in myofibrillar and sarcoplasmic proteins were also evaluated to assess their contributions to the loss of total protein. Synthesis of myofibrillar and sarcoplasmic proteins was estimated by intramuscular (IM) injection and total protein by intraperitoneal (IP) injection of flooding doses of 3H-phenylalanine. Total protein loss was greatest during the first 3 days following suspension and was a consequence of the loss of myofibrillar rather than sarcoplasmic proteins. However, synthesis of total myofibrillar and sarcoplasmic proteins diminished in parallel beginning in the first 24 hours. Therefore sarcoplasmic proteins must be spared due to a decrease in their degradation. In contrast, myofibrillar protein degradation increased, thus explaining the elevated degradation of the total pool. Following 72 hours of suspension, protein synthesis remained low, but the rate of myofibrillar protein loss diminished, suggesting a slowing of degradation. These various results show (1) acute loss of protein during unweighting atrophy is a consequence of decreased synthesis and increased degradation of myofibrillar proteins, and (2) sarcoplasmic proteins are spared due to slower degradation, likely explaining the sparing of plasma membrane receptors. Based on other published data, we propose that the slowing of atrophy after the initial response may be attributed to an increased effect of insulin. PMID- 8345804 TI - Influence of meal ingestion on insulin profiles following intraperitoneal delivery. AB - This study evaluated the effect of meal ingestion on intraperitoneal insulin absorption in type I diabetic patients with an implanted pump for long-term intraperitoneal insulin delivery. On four separate occasions, patients (n = 7) were administered 15 IU insulin as a 20-minute square-wave infusion using their implanted device; hypoglycemia was prevented by intravenous infusion of 10% dextrose at a variable rate. Two studies were performed during fasting conditions (n = 2 fasting tests) and two studies after the administration of an 800-kcal standard meal (n = 2 postprandial tests). An insulin peak of 630 +/- 545.4 pmol/L (mean +/- SD) in fasting tests and 696 +/- 420.5 pmol/L in postprandial tests was reached in the peripheral circulation after 45 +/- 11.7 and 45 +/- 14.7 minutes, respectively, with no significant difference between the two experimental conditions. Areas under the insulin curves were not significantly different in fasting and postprandial tests (51,500 +/- 34,278 v 50,916 +/- 20,558 pmol/L.min 1, respectively; NS). In type I diabetic patients receiving long-term intraperitoneal insulin therapy, the increase in splanchnic blood flow following ingestion of a standard meal does not accelerate the appearance of insulin in the peripheral circulation. PMID- 8345805 TI - Effect of pioglitazone on insulin receptors of skeletal muscles from high-fat-fed rats. AB - A new oral agent, 5-[4-[2-(5-ethyl-12-pyridyl)ethoxy]-benzyl]-2,4 thiazolidinedione, or pioglitazone, has been developed for the treatment of non insulin-dependent diabetes mellitus (NIDDM). We examined its effectiveness in high-fat-fed rats resistant to insulin. Administration of the agent (10 mg.kg-1 x d-1) for 2 weeks resulted in decreases in hyperlipidemia and hyperinsulinemia, indicating that insulin sensitivity had increased in vivo in high-fat-fed rats. To clarify the mechanism of the drug, we examined insulin binding and kinase activity of insulin receptors from muscles of both untreated and treated high-fat fed rats. Pioglitazone treatment did not change insulin binding in high-fat-fed rats, but increased insulin-stimulated autophosphorylation of insulin receptors to the level of control animals. Kinase activity toward an exogenous substrate, poly Glu4-Tyr1, in pioglitazone-treated high-fat-fed rats was also increased to the level of control animals. These results suggest that pioglitazone increases insulin sensitivity by activating tyrosine kinase activity of receptors in high fat-fed rats, and this drug appears to be a useful one with a new mode of action for the treatment of NIDDM with insulin resistance. PMID- 8345806 TI - Thermogenesis secondary to transdermal water loss causes growth retardation in essential fatty acid-deficient rats. AB - Manifestations of essential fatty acid (EFA) deficiency in rats include growth retardation and increased transdermal water loss. The extra metabolic energy requirement could be caused by greater evaporative water loss from the skin surface. To test this hypothesis, 38 weanling rats were randomly assigned to one of two environments, control (CE) at 20 degrees C and 40% humidity or warm/humid (WHE) at 30 degrees C and 90% humidity. Half of the 20 CE rats were fed an EFA adequate diet and the other 10 an EFA-deficient diet; the 18 WHE rats were also equally partitioned to the two diets. CE and WHE animals were independently group fed to maintain equal energy intakes within each environment. Weight gain at 90 days was lower for CE EFA-deficient rats than for CE EFA-adequate rats (P < .0001). Growth rates in the WHE to 140 days did not differ. Mean weights at 90 days were as follows: CE EFA-adequate, 196 g; CE EFA-deficient, 148 g; WHE EFA adequate, 148 g; WHE EFA-deficient, 135 g. In both CE and WHE animals, the triene/tetraene ratio of both serum and liver phospholipids (PL) was 100-fold greater for EFA-deficient versus EFA-adequate diets. PL fatty acids of liver in CE and WHE EFA-deficient rats contained 2.09 and 1.92 micrograms of 20:3 omega 9 per micrograms phosphorus (Pi), respectively, compared with 0.03 and 0.02 microgram 20:3 omega 9/micrograms Pi in CE and WHE EFA-adequate rats. These results indicate equivalent degrees of EFA deficiency in the two environments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345807 TI - Insulin modulates circulating endothelin-1 levels in humans. AB - Recent data indicate that insulin stimulates synthesis of the vasoconstrictor peptide endothelin-1 (ET-1) by cultured vascular endothelial cells in vitro. To determine whether insulin modulates ET levels in vivo and whether this effect is important in the pathogenesis of obesity-associated hypertension, we measured circulating immunoreactive ET-1 levels during euglycemic hyperinsulinemic clamps (20 mU/m2.min-1 for 120 minutes) in eight obese women (body mass index, 36 +/- 1 kg/m2) before and after 10 weeks on an 800-kcal/d protein-sparing liquid diet. During the clamp that preceded weight loss, insulin levels were increased from 17 +/- 2 to 51 +/- 3 mU/L and this was associated with an increment in ET-1 level from 28 +/- 3 to 33 +/- 3 pg/mL (P < .05). After weight loss, insulin levels were increased from 10 +/- 2 to 47 +/- 3 mU/L during the clamp, and there was a corresponding increase in ET-1 levels from 24 +/- 3 to 30 +/- 3 pg/mL (P < .025). The reduction in basal ET-1 level (from 28 +/- 3 to 24 +/- 3 pg/mL) with weight loss correlated strongly with the reduction in fasting immunoreactive insulin level (from 17 +/- 2 to 10 +/- 2 mU/L; r = .92, P < .01). The decrease in blood pressure with weight loss (from 130 +/- 6/73 +/- 3 to 118 +/- 4/72 +/- 3 mm Hg) did not correlate with the corresponding reduction in circulating ET-1 levels. These results indicate that insulin modulates ET-1 levels in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345808 TI - The serum insulin-like growth factor-II/mannose-6-phosphate receptor in normal and diabetic pregnancy. AB - The extracellular domain of the insulin-like growth factor-II/mannose-6-phosphate (IGF-II/Man-6-P) receptor is present in the circulation of several species including man. The purpose of the present study was to establish whether this truncated receptor is present in higher concentrations in fetal sera compared with adult sera and whether the metabolic status of the individual alters serum concentrations of this protein. Nondiabetic and diabetic pregnant women were studied throughout gestation, and at term fetal cord sera were obtained. Levels of IGF-I increased throughout pregnancy in normal and diabetic women. IGF-II levels significantly increased during the third trimester in both groups and levels of IGF-I and IGF-II were significantly elevated in fetal cord samples from diabetic women only. Serum samples were gel-filtered on Sephadex G-200, and column fractions were assayed for binding of radiolabeled IGF-II and IGF-I. There was specific binding (SB) of IGF-II in the void volume fractions in all samples examined. Normal women had 3% +/- 0.5% SB, whereas in cord sera SB was 5% +/- 0.7% and in pregnant sera 10% +/- 2%. There was no difference in SB in fetal cord or pregnant samples from normal and diabetic women. In addition, there was a peak of binding activity of both IGF-I and -II in gamma-globulin and postalbumin fractions of the columns in pregnant and nonpregnant women, but only in postalbumin fractions in fetal cord samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345809 TI - Inhibition of melatonin secretion by ethanol in man. AB - To determine whether ethanol inhibits nocturnal melatonin (MT) secretion, three experiments (A, B, and C) were performed in seven normal subjects. In A, ethanol at a dose of 0.34 g/kg was administered orally at 6:00, 8:00, and 10:00 PM. Each dose was increased to 0.52 g/kg in B. In C, water was substituted for ethanol. Blood samples for determination of serum MT levels were drawn every second hour between 6:00 PM and 8:00 AM. Urinary excretion of MT during the night was also determined. In A, serum ethanol reached a maximal level of 13 +/- 1 mmol/L at 12 midnight. In B, the corresponding maximum was 25 +/- 1 mmol/L. The higher alcohol dose inhibited nocturnal MT secretion by 20% +/- 5% (P < .01), whereas the lower dose lacked such effect. Urinary excretion of MT was left unaffected by alcohol at both doses. Five additional normal subjects were given alcohol as described above at a dose of 0.52 g/kg (experiment D). This induced mild nocturnal hypoglycemia as evidenced by a glucose decremental area (5.9 +/- 1.8 mmol/L.h) that differed significantly from zero (P < .05). To determine whether a reduced glucose delivery to pinealocytes might contribute to the decreased MT secretion in alcohol-intoxicated subjects, two experiments (E and F) were performed in eight healthy individuals. In E, ethanol was given orally as in B; three small oral doses of glucose were also given at 8:00 PM, 10:00 PM, and 12 midnight. In F, water was substituted for ethanol and glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345810 TI - Sodium-lithium countertransport activity is decreased after weight loss in healthy obese men. AB - Maximal red blood cell (RBC) sodium-lithium countertransport activity has been consistently related to essential hypertension and may be a marker for risk of developing hypertension. Although there is strong evidence for genetic control of sodium-lithium countertransport, increasing evidence suggests that obesity and insulin-glucose metabolism are related to countertransport activity. This study was performed to determine whether countertransport activity decreases with weight loss in healthy obese adults. Forty-five healthy, white, obese adults were studied at baseline and after 6 months of behavioral dietary intervention. Weight loss was 11.5 kg (25.4 lb) in 24 men and 8.1 kg (17.8 lb) in 21 women. Sodium lithium countertransport activity decreased 55.0 mumol Li/L RBC/h in men (P < .001, paired t test) and 14.6 mumol Li/L RBC/h in women (NS). Change in countertransport activity was correlated with change in body mass index (BMI) in men (r = .52, P < .01) and women (r = .27, NS) and was also strongly correlated with change in fasting glucose levels in both men and women (r = .50 and r = .56, respectively; P < .01) and with change in fasting insulin levels in men (r = .42, P = .04). Change in countertransport activity was not significantly related to change in physical exercise or serum lipid levels. There was a large decrease in systolic blood pressure in men (10.0 mm Hg, P < .001) and a smaller decrease in women (4.1 mm Hg, P < .05). These changes were significantly correlated with change in weight, but not with change in countertransport or baseline countertransport activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345811 TI - Stimulation of brain natriuretic peptide release from the heart by thyroid hormone. AB - This study was designed to examine the involvement of thyroid hormone in the release of brain natriuretic peptide (BNP) from the heart. We measured plasma immunoreactive BNP (ir-BNP) concentrations in patients with untreated hyperthyroidism. We also measured BNP values in experimental rats with hyperthyroidism induced by thyroxine (T4) and in rats with hypothyroidism induced by propylthiouracil (PTU). The in vitro effects of triiodothyronine (T3) and T4 on the release of BNP were examined in newborn rat atrial and ventricular myocytes in primary culture. Plasma BNP levels were increased in hyperthyroid patients compared with normal control subjects. Plasma BNP levels were increased in hyperthyroid rats and decreased in hypothyroid rats compared with euthyroid rats. Plasma BNP level was correlated with serum T4 level in hyperthyroid patients and hyperthyroid rats. A major component of ir-BNP in plasma from hyperthyroid patients was human BNP-32 and that in plasma from hyperthyroid rats was rat BNP-45. T4 and T3 stimulated release of ir-BNP from both cultured atrial and ventricular myocytes in a dose-dependent manner. Plasma BNP concentration is frequently increased in hyperthyroidism, and thyroid hormone may regulate BNP release from both atrial and ventricular myocytes. PMID- 8345813 TI - Hepatic extraction of insulin after stimulation of secretion with oral glucose or parenteral nutrients. AB - To determine whether hepatic extraction of insulin differs when glucose is administered by parenteral and physiological routes, we studied responses to oral glucose and to intravenous (IV) infusion of glucose or glucose plus arginine in normal volunteers. As in earlier studies, when IV glucose infusions were empirically programmed to to produce isoglycemic responses with 50 or 75 g oral glucose, ratios of integrated areas under concentration curves for immunoreactive C-peptide (CP) to insulin in the plasma were higher with IV than with oral glucose. Mean values +/- standard errors for these ratios in paired experiments with 50 g oral glucose were 5.6 +/- 0.66 compared with 8.3 +/- 1.4 with IV glucose (P < .03). With 75 g oral glucose, the corresponding values were 4.3 +/- 0.38 and 7.8 +/- 0.50 (P < .001). These results suggest that hepatic extraction of insulin is diminished when insulin secretion is potentiated by enteroinsular mechanisms after oral glucose administration. To determine whether this phenomenon is related to the route of administration of glucose or to the enhancement of insulin secretion with oral glucose, programmed IV infusions of glucose were used to elicit excursions of plasma CP similar to those obtained after 50 g oral glucose, and programmed infusions of glucose plus arginine were used to elicit excursions of plasma CP similar to those obtained after 75 g oral glucose. Plasma levels of immunoreactive gastric inhibitory polypeptide (GIP) increased substantially after ingestion of 75 g glucose, but did not change during isoglycemic IV glucose infusions or during IV infusions of glucose plus arginine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345812 TI - Response of cholesterol synthesis to cholesterol feeding in men with different apolipoprotein E genotypes. AB - To investigate the influence of dietary cholesterol level and apolipoprotein (apo) E polymorphism on cholesterol synthesis, seven apo E2/- and six apo E4/- normolipidemic subjects consumed self-selected diets containing low cholesterol ([LC] 250 mg/d) and high cholesterol ([HC] 800 mg/d) levels for approximately 20 days. On day 20, subjects were given 0.7 g deuterium oxide (D2O)/kg body water followed by maintenance doses. Cholesterol synthesis was measured as the uptake rate of D into plasma free cholesterol over 24 hours. Serum total cholesterol levels were higher (P < .05) in the apo E4/- versus apo E2/- group over both dietary periods. No influence of dietary cholesterol content on serum levels was observed, nor was there an effect of apo E genotype or dietary cholesterol level on cholesterogenesis. However, a genotype-independent association was observed between both cholesterogenesis (P < .001) and the increase in cholesterogenesis (P = .05) with the change in serum total cholesterol level subsequent to high cholesterol feeding. These findings suggest that (1) apo E genotype is not associated with cholesterol synthesis rate in subjects on self-selected diets, and (2) hyporesponders to a dietary cholesterol challenge display higher synthetic rates than hyperresponders. The observation of lower cholesterol synthesis in individuals with the largest increases in serum cholesterol level after a dietary cholesterol challenge suggests a passive rather than dominant role of cholesterol synthesis in regulating serum levels. PMID- 8345814 TI - Carbohydrate oxidation rates in patients with anorexia nervosa. AB - Twenty-one hospitalized anorexia nervosa (AN) patients underwent a 50-g glucose challenge. All patients were then fed for 10 days and divided into two groups based on weight gain. Group AN-a (n = 10) gained little or no body weight over the 10-day period, whereas the second group, AN-b (n = 11), did gain weight during the same period. A third group of normal women (n = 10) served as control subjects (NC). Following ingestion of 50 g of glucose, group AN-a showed virtually the same nonprotein respiratory quotient (NPRQ) response as group NC. Group AN-b showed significant increases in basal and glucose-stimulated NPRQ and carbohydrate oxidation rate responses compared with group NC. Serum insulin responses in both AN groups were lower than those of group NC. These results indicate that insulin sensitivity in both liver and muscle may be increased in AN patients, and that refeeding tends to increase body weight rapidly in some patients due to this mechanism. PMID- 8345816 TI - Insulin therapy normalizes GLUT1 glucose transporter mRNA but not immunoreactive transporter protein in streptozocin-diabetic rats. AB - Previous studies have shown that the principal glucose transporter isoform within the blood-brain barrier (BBB) is GLUT1, and that GLUT1 mRNA is upregulated and immunoreactive GLUT1 protein is downregulated in rats with streptozocin (STZ) induced experimental diabetes. The present studies investigate effects of insulin therapy on both GLUT1 mRNA and immunoreactive GLUT1 protein in brain capillaries isolated from control (CO), diabetic (DM), and insulin-treated diabetic (IRx) rats. The following variables were measured: serum glucose levels, rat brain capillary immunoreactive GLUT1 level by quantitative Western blotting, and rat brain capillary GLUT1 and actin mRNA levels by quantitative Northern blotting. Serum glucose levels were 6.4 +/- 1.2, 30.3 +/- 3.2, and 3.7 +/- 1.7 mmol/L in CO, DM, and IRx rats, respectively. Brain capillary immunoreactive GLUT1 transporter protein level was 53% +/- 13% of CO values in DM rats, and this value was unchanged with insulin treatment. GLUT1 mRNA level in rat brain was increased to 131% +/- 8% of CO values in DM rats and was 80% +/- 5% of CO values in IRx rats. In conclusion, short-term insulin therapy in rats with STZ-induced diabetes normalizes BBB GLUT1 mRNA level, but does not normalize depressed immunoreactive GLUT1 protein level. PMID- 8345815 TI - Prevalence and pathophysiology of impaired glucose tolerance in three different high-risk white groups. AB - Insulin resistance and beta-cell function were assessed by a continuous infusion of glucose in the following three groups of white subjects at risk of developing impaired glucose tolerance and diabetes: 41 subjects who were the offspring of patients with type II diabetes, 26 general-population subjects with an increased fasting plasma glucose level of at least 5.6 mmol/L on screening, and 22 subjects who had had gestational diabetes but were now nondiabetic. Subjects had a mean (+/- 1 SD) age of 43 +/- 9 years and a body mass index (BMI) of 27 +/- 5 kg/m2. Subjects with previously increased fasting glucose levels were significantly more insulin resistant than a control group, taking into account BMI, age, and gender (% normal insulin sensitivity [%], 59 [50 to 79] v 87 [73 to 96]; P < .005), and previously gestationally diabetic subjects showed greater impairment of beta-cell function (% normal beta-cell function [% beta], 69 [60 to 87] v 97 [89 to 105]; P < .005). Diabetes (defined by World Health Organization criteria) or impaired glucose tolerance (defined as an achieved plasma glucose concentration [APG] > 95th percentile of an age- and weight-matched population) was identified in 22% of family members, 31% of fasting hyperglycemic subjects, and 41% of previously gestationally diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345817 TI - The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. AB - The cardiovascular risk factor plasminogen activator inhibitor type 1 (PAI-1) has been associated with abdominal obesity, hypertension, hypertriglyceridemia, hyperinsulinemia, glucose intolerance, and type II diabetes, conditions known to be linked with insulin resistance. To determine whether PAI-1 is related to insulin resistance, we studied nine obese nondiabetics and 10 obese type II diabetics by means of a sequential hyperinsulinemic euglycemic clamp study. Plasma PAI-1 antigen (Ag) correlated significantly with peripheral insulin resistance, represented by the insulin level at which peripheral glucose uptake (PGU) is half-maximal ([ED50PGU] r = .87, P < .001). Multiple regression analysis including indices of hepatic and peripheral insulin action, fasting plasma insulin levels, triglyceride levels, blood pressure (BP), waist to hip ratio (WHR), and body mass index (BMI) disclosed ED50PGU to account for 76% of the variance of PAI-1 Ag. We suggest that PAI-1 contributes to the increased cardiovascular risk encountered with insulin resistance. PMID- 8345818 TI - A practical equation to predict resting metabolic rate in older men. AB - The accuracy of previous equations for predicting resting metabolic rate (RMR) in healthy older men is questionable because they are based on limited sample sizes and the absence of cross-validation procedures. The purposes of this study were to (1) examine biological predictors of RMR in healthy older men; (2) develop a practical equation to predict RMR from easily measured variables and examine its accuracy using cross-validation procedures; and (3) test the validity of existing equations in the literature to predict RMR in older men by comparison with measured RMR values. RMR, body composition, anthropometric measurements, leisure time activity (LTA), maximal aerobic power (VO2max), energy intake, and plasma thyroid hormone levels were determined in 89 healthy older men aged 50 to 78 years. Stepwise regression analysis showed that RMR was best predicted by fat free weight ([FFW] R2 = 85%), free 3,5,3'-triiodothyronine (T3) level (R2 = 1%), and VO2max (R2 = 1%); these variables predicted RMR with a residual error of +/- 30 kcal/d. A practical equation was developed in a randomly selected subsample (N = 61) using easily measured variables as potential predictors, and was successfully cross-validated in a random subsample of older men (N = 28). The pooled equation to predict RMR is as follows: RMR (in kilocalories per day) = 9.7 (weight in kilograms) - 6.1 (chest skinfold thickness in millimeters) - 1.8 (age in years) + 0.1 (leisure time activity [LTA] in kilocalories per day) + 1,060. These variables accounted for 76% (R2) of the variation, and predicted RMR with a residual error of +/- 42 kcal/d.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345819 TI - Organ clearance of tyrosyl-arginine and its effect on amino acid metabolism in young sheep. AB - In a long-term multiple-catheter sheep model (n = 5), organ clearance of the dipeptide tyrosyl-arginine (TyrArg) and its effects on interorgan amino acid metabolism were investigated. Clearance by hindlimb and splanchnic tissues was measured during infusion into the external iliac artery and superior mesenteric artery, respectively. The hindlimb, intestine, and total splanchnic region removed 32% +/- 9.2% (mean +/- SE), 23% +/- 15%, and 33% +/- 24%, respectively, of the amount of TyrArg infused. There was a large release of tyrosine and arginine when TyrArg was infused into either the hindlimb or intestine, which was quantitatively similar to the TyrArg taken up by these organs. However, across the total splanchnic region, the baseline influx of tyrosine and arginine was not altered by infusion of TyrArg. During either clearance study, only trace amounts of TyrArg or its constituent amino acids were excreted in urine. Infusion of TyrArg produced the following effects on interorgan amino acid metabolism: (1) a reduction in the initial efflux of phenylalanine, leucine, isoleucine, and valine from the hindlimb; (2) a reduction in net efflux of citrulline by the intestine and total splanchnic tissues; and (3) a reduction in efflux of arginine and uptake of citrulline from the kidney. In conclusion, we have shown that TyrArg is cleared from the bloodstream by hindlimb (predominantly muscle) and splanchnic tissues. These results indicate that TyrArg taken up by the hindlimb and intestine was hydrolyzed to its constituent amino acids, which were released quantitatively into the circulation. Of the tissues studied, only the liver appeared to use the amino acids liberated from hydrolysis of TyrArg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345820 TI - Body composition in children and Tanner's stages: a study with dual-energy x-ray absorptiometry. AB - Total body bone mineral content (TBBM), body fat content (BF), and fat-free mass (FFM) were measured in 154 children using dual-energy x-ray absorptiometry (DEXA). Total body calcium level (TBCa) was calculated from TBBM. Children were divided into groups according to Tanner's stages 1, 2, 4, and 5. Children in stage 3 were not included in the study in order to better differentiate between prepubertal and postpubertal individuals. We did not find differences in TBBM, TBCa, BF, and FFM between Tanner's stages 1 and 2 or between sexes. TBBM and TBCa in stages 4 and 5 were lower in girls than in boys (P < .001 and P < .01, respectively); no differences were observed between girls of both groups, although boys showed significant differences (P < .05). FFM for both sexes was lower in stages 1 and 2 than in stages 4 and 5. Girls showed lower FFM (P < .001) than boys in stages 4 and 5; FFM was higher in boys in stage 5 than in those in stage 4 (P < .005), and the same was true for girls (P < .002). Boys in stage 4 had less BF than girls (P < .005), and the same was true for stage 5 (P < .001). Girls in stages 4 and 5 had greater BF than those in stages 1 and 2 (P < .001). These differences suggest that as boys go through puberty, both TBBM and FFM continue to increase, while in girls only BF and FFM increase. These data indicate clear sex differences in somatic postpubertal development. PMID- 8345821 TI - Is exercise training effective in preventing diabetes mellitus in the Otsuka-Long Evans-Tokushima fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus? AB - We determined whether exercise training is effective in preventing the development of diabetes mellitus in a model rat (Otsuka-Long-Evans-Tokushima Fatty [OLETF]) with non-insulin-dependent diabetes mellitus (NIDDM). Thirty male OLETF rats aged 5 weeks were assigned to one of the following three groups: trained rats placed individually in an exercise wheel (EW) cage, EW-control rats housed in the same cages equipped with a fixed rotatory wheel, and sedentary rats maintained two or three to a conventional cage. Eight male diabetes-resistant Long-Evans rats were used as nondiabetic controls. At 24 weeks of age, the trained, EW-control, sedentary, and nondiabetic control rats weighed an average of 445, 559, 621 and 513 g and had abdominal fat deposits of 16, 55, 67, and 23 g, respectively. The mean amount of exercise of trained rats was 5,243 m/d. At 24 weeks of age, the cumulative incidences of diabetes mellitus in sedentary and EW control rats were 78% and 50%, respectively, while neither trained nor nondiabetic control rats became diabetic. Fasting and 120-minute plasma immunoreactive insulin (IRI) levels after oral glucose administration were significantly lower in the trained group than in the other groups. In vivo insulin-stimulated glucose uptake as measured with a euglycemic clamp was reduced 37% in sedentary rats and increased 35% in trained rats compared with that in nondiabetic control rats. Morphological studies on the pancreas of sedentary and EW-control rats showed enlarged multilobulated fibrotic islets, whereas sections of islets from trained rats appeared normal but slightly enlarged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345823 TI - Glycosylated serum proteins and glycosylated hemoglobin in the assessment of glycemic control in insulin-dependent and non-insulin-dependent diabetes mellitus. AB - To evaluate the relative value of glycosylated serum proteins (GSPs) versus glycosylated hemoglobin (HbA1c) in assessing glycemic control in diabetes mellitus, we performed regular monitoring of GSPs and HbA1c in 30 subjects with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) who performed frequent self-glucose monitoring. Analysis of the relationship between patterns of glycemic control and GSPs and HbA1c demonstrated that subjects with IDDM and NIDDM appeared similar when the more traditional indicators of glycemic control such as mean blood glucose level (166.9 +/- 20.9 v 177.4 +/- 39.6 mg/dL) or HbA1c (83.57 +/- 12.8 v 80.24 +/- 15.7 mmol hydroxymethyl furfuraldehyde [HMF]/mol hemoglobin [Hgb]) were used. However, when GSP levels or the standard deviation of mean glucose levels (SDMG) were used to assess glycemic control, higher levels were found in subjects with IDDM (52 +/- 10.3 mg/g protein and 28.59 +/- 7.60 mg/dL) versus NIDDM (44.6 +/- 15.2 mg/g protein and 21.6 +/- 15.9 mg/dL). Using multivariate analysis, GSPs were predictive of SDMG (P = .046), whereas HbA1c added no significant further information (P = .27). Our results suggest that GSPs may be more sensitive than HbA1c assay to the greater fluctuations in blood glucose levels generally associated with IDDM. PMID- 8345822 TI - Elevation of 2-methylcitric acid I and II levels in serum, urine, and cerebrospinal fluid of patients with cobalamin deficiency. AB - Citrate synthase catalyzes the condensation of acetyl-coenzyme A (CoA) and oxaloacetic acid to form citric acid. The enzyme also catalyzes the condensation of propionyl-CoA and oxaloacetic acid with a maximal reaction velocity (Vmax) approximately 10(-4) times that of acetyl-CoA to form 2-methylcitric acid, which contains two asymmetric carbon atoms and exists as two pairs of related enantiomers designated as 2-methylcitric acid I and II. Cobalamin (Cbl) deficiency can lead to increases in intracellular levels of propionyl-CoA. To assess the magnitude of increased synthesis of 2-methylcitric acid in Cbl deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured 2-methylcitric acid levels in serum and cerebrospinal fluid (CSF) of normal subjects and patients with clinically confirmed Cbl deficiency. The normal range for 2-methylcitric acid level was 60 to 228 nmol/L for serum in 50 normal blood donors and 323 to 1,070 nmol/L for CSF in 19 normal subjects. In 50 patients with clinically confirmed Cbl deficiency, values for 2-methylcitric acid in serum ranged from 93 to 13,500 nmol/L; 44 (88%) had values above the normal range. In five patients with clinically confirmed Cbl deficiency, levels of the sum of 2-methylcitric acid I and II ranged from 1,370 to 16,300 nmol/L in CSF, and all five (100%) patients had levels above the normal range. We conclude that levels of 2-methylcitric acid are elevated in serum and CSF of most patients with Cbl deficiency. PMID- 8345825 TI - Dental clues. PMID- 8345824 TI - Abdominal obesity is associated with insulin resistance and reduced glycogen synthetase activity in skeletal muscle. AB - Insulin resistance is commonly associated with obesity. The present study was performed to investigate the relative importance of total fat mass versus localization of adipose tissue in insulin-stimulated glucose disposal (Rd) and skeletal muscle glycogen synthase (GS) activity in obese individuals. Twenty obese women with an average body mass index (BMI) of 37.8 +/- 1.3 kg/m2 and a waist to hip ratio (WHR) ranging from 0.78 to 1.02 were examined during basal conditions and following hyperinsulinemia (hyperinsulinemic euglycemic clamp). To accurately determine body composition, the following three methods were used: anthropometric measurements, dual-energy x-ray absorptiometry scanning (DEXA scan), and bioelectric impedance measurements. In addition, indirect calorimetry and muscle biopsy were performed. Insulin-stimulated glucose Rd was negatively correlated with WHR (R = -.52, P < .025) whereas there were no correlations with BMI or percent fat (R = .16, NS and R = .16, NS, respectively). Furthermore, a negative correlation between WHR and insulin stimulation of GS activity in skeletal muscle was found (R = -.62, P < .005). In contrast, BMI and percent fat were not correlated with the insulin effect on GS activity in skeletal muscle (R = .34, NS and R = -.35, NS, respectively). The concentration of nonesterified fatty acids (NEFA) during hyperinsulinemia was strongly correlated with WHR and abdominal localization of adipose tissue (determined by DEXA-scan; R = .60, P < .005 and R = .60, P < .007, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345826 TI - Slander and exhumation. PMID- 8345827 TI - The Children Act 1989: the lawyer and the doctor--conflict or co-operation. PMID- 8345828 TI - The M'Naghten Rules--the story so far. PMID- 8345829 TI - Hypercalcemia in association with acute renal failure and rhabdomyolysis. Case report and literature review. AB - The syndrome of hypercalcemia during the course of acute renal failure (usually associated with rhabdomyolysis) occurs most commonly in young men with very severe renal failure. Although fewer than 90 such patients have been reported, the prevalence of hypercalcemia in patients with rhabdomyolysis-associated renal failure averages 30%. Hypercalcemia occurs most commonly in the diuretic phase and resolves spontaneously. The mean duration of hypercalcemia is 14 days. The pathogenesis of this syndrome has not been clearly defined. In the rare instances where it has been measured, intact PTH is suppressed. In contrast, both elevated and suppressed values of plasma 1,25-dihydroxyvitamin D have been reported. The release of calcium from ectopic calcification in damaged muscle tissue provides a potential explanation for this syndrome. Therapy for the hypercalcemia should generally be conservative given its self-limited nature. PMID- 8345830 TI - Myocardial texture and cardiac calcification in uremia. AB - Seventy patients with advanced chronic renal failure were examined by 2D echocardiography in an effort to determine the prevalence of changes in myocardial texture and of valvular calcification. Changes in myocardial texture may be due to calcium deposition in the myocardium, the relationship between changes in myocardial texture and factors that may enhance myocardial calcification (blood levels of parathyroid hormone, PTH, and calcium-phosphorus product) were also evaluated. Myocardial texture was abnormal in 36 patients. In 68 patients, structural calcification could be assessed; a high degree of calcification was found. No correlation was found between either the echocardiographic parameter and blood levels of PTH or calcium-phosphorus product. We conclude that myocardial textural changes and intracardiac calcification are common in chronic renal failure and that these abnormalities do not correlate with blood PTH levels or calcium-phosphorus product. PMID- 8345831 TI - Peripheral metabolism of branched-chain keto acids in patients with chronic renal failure. AB - Peripheral tissue metabolism of branched-chain amino acids (BCAA) and branched chain keto acids (BCKA) in the postabsorptive state was evaluated in 8 patients with chronic renal failure (CRF) and 7 controls by measuring the arterial-deep forearm venous differences for BCAA and BCKA. Arterial whole blood levels of BCAA and BCKA were also measured in an additional 7 patients and 11 controls. In CRF, total BCKA levels are reduced owing to a decrease in ketoisocaproic acid (KICA) and ketoisovaleric acid (KIVA) levels, parallel to changes in BCAA levels, whereas levels of ketomethylvaleric acid (KMVA) are not different from controls. Both in normal conditions and in patients, arterial levels of individual BCAA are directly correlated with arterial levels of the corresponding BCKA. However, in CRF, the ratios of leucine to KICA and of isoleucine to KMVA are increased. A direct correlation between KICA and HCO3- levels is observed. In CRF, the release of leucine and valine as well as of KICA and KMVA from peripheral tissues is reduced, whereas KIVA is neither released nor taken up by the forearm. The lack of KICA release from peripheral tissues likely accounts for its low circulating levels. The depressed peripheral release of leucine associated with the lack of KICA release suggests an increased degradation of leucine which proceeds beyond the transamination step. PMID- 8345832 TI - Hypernatremia in the acutely ill elderly patients: role of impaired arginine vasopressin secretion. AB - Hypernatremia, a common finding among the elderly, is believed to be due to water deficit. In the present study, in 12 consecutive hospitalized elderly patients (mean age 82.2 years) with moderate to severe hypernatremia (mean serum sodium 166.9 mEq/l), inappropriately low plasma levels of vasopressin were found in relation to serum osmolality (mean 1.8 pg/ml and 343 mosmol/l, respectively). All patients but 1 were hospitalized with acute febrile disease and all but 2 had underlying neurological disease. Hypernatremia persisted for at least 3 days despite the patients' rehydration. It seems, therefore, that temporary hypernatremia in elderly patients with acute febrile disease, especially in the presence of underlying neurological disorder, reflects an inadequate vasopressin response to the hyperosmolar state. PMID- 8345833 TI - Potassium intake and urinary calcium excretion in healthy subjects. AB - Potassium depletion increases and potassium supplementation decreases urinary calcium excretion. To determine whether these experimental observations have any significance in healthy free living subjects, we measured 24 h urinary calcium, sodium, potassium and serum parathyroid hormone (PTH) in 142 healthy young (aged 18-40 years) female Chinese subjects. Sodium excretion and potassium excretion were positively correlated with calcium excretion (r = 0.494, p < 0.0001 and r = 0.181, p = 0.031, respectively). However stepwise multiple regression analysis showed that only urinary sodium excretion contributed to the excretion of calcium. We conclude that in free living subjects potassium intake has little effect on calcium excretion. PMID- 8345834 TI - Early detection of breast cancer: implications for nurses. PMID- 8345835 TI - Voluntary vs. mandatory continuing education. PMID- 8345836 TI - Clinical speaking--certification, licensure and continuing education in advanced practice. PMID- 8345837 TI - Surveillance for primary and secondary syphilis--United States, 1991. AB - PROBLEM/CONDITION: From 1986 through 1990, an epidemic of syphilis occurred throughout the United States. In 1991, the number of reported cases of primary and secondary (P&S) syphilis in the United States declined for the first time since 1985. REPORTING PERIOD COVERED: To examine how this decline reflected sex specific, race/ethnicity-specific, and regional patterns of syphilis morbidity, we analyzed data for syphilis cases reported to CDC from 1984 through 1991. DESCRIPTION OF SYSTEM: Summary data for cases of syphilis reported to state health departments were sent quarterly and annually to CDC. The quarterly data from each state included total number of syphilis cases by sex, stage of disease (primary, secondary, early latent, and late latent), and source of report (public or private). The annual data from each state included total number of P&S syphilis cases by sex, racial/ethnic group (white, not of Hispanic origin; black, not of Hispanic origin; Hispanic; Asian/Pacific Islander; or American Indian/Alaskan Native), 5-year age group, and source of report. RESULTS: The decline in both the number and rate of reported syphilis cases in 1991 occurred in every racial group in the United States and in both sexes. This decline also occurred in every region of the United States except the Midwest, where the total P&S syphilis rate increased 37.3% from 1990 through 1991. Despite the increase in syphilis rates in the Midwest, the highest rates of P&S syphilis in 1991 were reported from the South. INTERPRETATION: The reasons for the decline in syphilis are unclear. No data exist to conclusively identify which STD control program activities affected the level of syphilis morbidity or to what extent those activities may have contributed to the decline. Changes in drug use and limited immunity to Treponema pallidum may have accounted for some of the decrease in syphilis incidence. Higher levels of poverty in the South and poor access to health-care services associated with poverty probably contributed to continued high levels of disease transmission in the South. ACTIONS TAKEN: Better evaluation of STD control program activities will be necessary to help determine the most effective strategies for preventing and controlling syphilis in different high-risk populations. PMID- 8345838 TI - An evaluation of surveillance for Chlamydia trachomatis infections in the United States, 1987-1991. AB - PROBLEM/CONDITION: Chlamydia is the most common sexually transmitted bacterial pathogen in the United States; however, no precise data on the prevalence and incidence of chlamydia infection are available because currently no comprehensive national surveillance system exists for chlamydia. Despite the absence of such a system, states do report numbers of male and female chlamydia cases to CDC on a quarterly basis. REPORTING PERIOD COVERED: This report summarizes and reviews the chlamydia surveillance data received by CDC from 1987 through 1991. DESCRIPTION OF SYSTEM: Summary data on cases of chlamydia reported to state health departments were sent quarterly to CDC in Atlanta, Georgia. The quarterly data from each state included total number of chlamydia cases by sex and by source of report (public, private). RESULTS: From 1987 through 1991, the number of states with legislation mandating reporting of chlamydia increased twofold. The reported chlamydia rate from those states also doubled during the same time period, from 91.4 cases per 100,000 population in 1987 to 197.5 cases per 100,000 population in 1991. INTERPRETATION: This twofold increase in the rate of chlamydia reported to CDC did not represent a doubling in chlamydia prevalence or incidence during this time period. Instead, the increase resulted from the increase in the number of states with reporting laws and from the initial attempts of those states to identify and report diagnosed chlamydia infections. ACTIONS TAKEN: More accurate measures of the number of chlamydia infections and of trends in the chlamydia infection rate are needed to justify, develop, and evaluate public health programs to control chlamydia infections. An outline of possible surveillance activities for local communities is presented. PMID- 8345839 TI - Sentinel surveillance for antimicrobial resistance in Neisseria gonorrhoeae- United States, 1988-1991. The Gonococcal Isolate Surveillance Project Study Group. AB - PROBLEM/CONDITION: The prevalence of antimicrobial resistance in Neisseria gonorrhoeae in the United States has been increasing since the mid-1970s. DESCRIPTION OF SYSTEM: The Gonococcal Isolate Surveillance Project (GISP) was established in 1986 to monitor trends of antimicrobial resistance in N. gonorrhoeae. GISP is a sentinel surveillance system consisting of 26 publicly funded sexually transmitted disease clinics and five regional laboratories. At each clinic, urethral isolates are obtained from the first 20 men diagnosed with gonorrhea each month; these isolates are shipped to one of the regional laboratories, where the susceptibilities of the organisms to a panel of antibiotics are determined. REPORTING PERIOD COVERED: This report describes the results of surveillance for antimicrobial resistance in N. gonorrhoeae from January 1991 through December 1991. These results are compared with data obtained from January 1988 through December 1990. RESULTS AND INTERPRETATION: In the 1991 GISP sample, 32.4% of isolates were resistant to penicillin or tetracycline. The proportions of isolates with high-level, plasmid-mediated resistance to penicillin, tetracycline, or both drugs have increased significantly (p < 0.001) in the GISP sample during 1988-1991. No documented clinical treatment failures have been related to decreased susceptibility of N. gonorrhoeae to either ceftriaxone or ciprofloxacin, which belong to the classes of antibiotics currently recommended for gonococcal therapy. ACTION TAKEN: Because of the demonstrated ability of N. gonorrhoeae to develop resistance to antimicrobial agents, surveillance to guide therapy recommendations will be continued. PMID- 8345840 TI - Frontiers in gastroenterology. In honor of dedication of the Dr. Henry D. Janowitz Division of Gastroenterology, The Mount Sinai Hospital. PMID- 8345841 TI - Henry D. Janowitz and American gastroenterology. PMID- 8345842 TI - Modern concepts in pancreatitis. AB - A great deal remains to be learned about the pathophysiology, natural history, and treatment of acute and chronic pancreatitis. As we consider problems in treatment, we would be well advised to consider these words of Dr. Henry Janowitz: "Gastroenterologists are physicians who know how to think about and manage patients who have gastrointestinal problems." (44). To the extent that we heed these words and always give serious thought to what we are trying to achieve, we will provide greater help for our patients. PMID- 8345843 TI - New frontiers in gastrointestinal hormones. PMID- 8345844 TI - Current advances in gastrointestinal immunology. PMID- 8345845 TI - Evolution of the controlled clinical trial. PMID- 8345846 TI - Advances in knowledge of inflammatory bowel disease at Mount Sinai Medical Center. PMID- 8345847 TI - Obscure gastrointestinal bleeding. AB - I want to convey the notion that enteroscopy has opened many doors, and continues to open up more doors, in understanding and diagnosing diseases of the small intestine. The true nature of small-bowel angiodysplasia is still unanswered. It seems unlikely that the lesions in the small bowel are similar to the lesions that Scott Boley talks about in the right colon. I doubt that the intermittent obstruction to venous outflow, theorized in the colon, is the pathophysiologic change in the small intestine. Those studies, trying to look for the changes that Boley described, need to be done. We are trying to better characterize angiodysplasia of the small intestine, understanding where they occur, with how many lesions, and whether they are associated with any other illnesses. We are looking at the association of small-bowel vascular lesions with lesions in the stomach and colon. Enteroscopy will in the future, we hope, answer these questions. Enteroscopy, especially push enteroscopy, can help us with the treatment of angiodysplasias. We are now evaluating new instruments that reach not just two feet beyond the ligament of Treitz, but the entire jejunum, reaching 6 feet beyond the ligament of Treitz (16). Enteroscopy facilitates clinical research, can be used in patient care, and guides treatment. PMID- 8345848 TI - The pharmacology of antiinflammatory agents: a new paradigm. PMID- 8345849 TI - Asthma: an inflammatory disease. PMID- 8345850 TI - Prevalence of atopy in an inner-city asthmatic population. AB - Seventy-three patients at The Mount Sinai Hospital Emergency Room were investigated to determine the prevalence of atopy in asthma in a predominantly black and Hispanic inner-city population. Serum IgE levels and radioallergosorbent tests (RASTs) to eight common inhalant allergens were measured in both the asthmatic group and a nonasthmatic emergency-room control group. The mean total IgE level for the asthma group was 263.8 IU/mL compared to 63.8 IU/mL in the control group (p = 0.032), and 60% of the asthmatics had IgE levels in the atopic range (> 100 IU/mL). Increases in IgE were associated with age under 50 years but did not reach statistical significance. Cockroach, dust mite, cat, and dog were the most common RASTs in the asthmatic group; there were no positive RASTs in the control group. There was a correlation (p = 0.04) between age (less than 50 years) and increased numbers of positive RASTs. These results are similar to those of other studies that have associated atopy with asthma in rural and suburban populations. These data demonstrate that atopy is common in the asthmatic patients seen in The Mount Sinai Hospital Emergency Room and strongly suggest that management of atopic factors should become routine in the care of adult asthmatic patients. PMID- 8345851 TI - Oligoclonal banding in AIDS and hemophilia. AB - Hypergammaglobulinemia is a consistent finding in patients within the AIDS spectrum and with hemophilia A. Serum samples from patients with these conditions were analyzed for the presence of oligoclonal banding, using a high-resolution serum protein electrophoresis system. The incidence of banding is significantly greater in well homosexuals who are HIV-antibody positive and in patients with pre-AIDS-related complex, AIDS-related complex, AIDS with opportunistic infections, and AIDS with Kaposi's sarcoma than in normal blood donors. The incidence of banding is similar to controls in patients with hemophilia who have received either no blood products, cryoprecipitate only, or limited infusions of factor VIII concentrate. In patients who have received frequent infusions of factor VIII concentrate, the incidence of banding significantly increases. Thirteen of sixty-seven hemophiliac patients developed AIDS or symptoms related to HIV infection independent of their banding pattern. We hypothesize that the bands are not diagnostic of AIDS, but seem to correspond with disease progression, and that they are absent early in the disease, appear later in the course, and may disappear with advanced disease. PMID- 8345852 TI - Gold-induced colitis: a case report and review of the literature. AB - A case of severe colitis requiring subtotal colectomy following administration of 35 mg Solganal b for intractable arthritis is described. Abdominal pain and watery diarrhea developed six weeks after the last dose of gold. Colonoscopy revealed mucosal edema and ulceration of the entire colon. Supportive measures failed and the patient required subtotal colectomy. Review of the literature revealed 29 cases, ranging in severity from limited ileal involvement to fulminant panenteritis. Most of the patients responded to intravenous fluids, steroids, and antibiotics, but four required surgery. The case described is notable for the delay in appearance of abdominal symptoms following the cessation of gold therapy. The mechanism of injury is unknown. Abdominal complaints in a patient who has received gold therapy, especially parenteral, merit strict attention, even if occurring several weeks after the final dose, and the diagnosis of gold colitis should be entertained. PMID- 8345853 TI - Progressive nemaline rod myopathy in a woman coinfected with HIV-1 and HTLV-2. AB - Nemaline-rod myopathy was recently reported in eight young males infected with human immune deficiency virus type 1 (HIV-1). A 41-year-old woman had a 2-year history of progressive proximal-muscle weakness. Muscle biopsy demonstrated the presence of nemaline rods, predominantly in type 1 fibers. She was coinfected with HIV-1 and HTLV-2, as evidenced by positive polymerase chain reaction and serology. There was no lymphopenia or CD4 lymphopenia, despite an abnormal T-cell subset ratio, high CD8 count, skin anergy, and depressed in vitro response to mitogens. This case raises the possibility that dual infection may play a role in the pathogenesis of the rare nemaline-rod myopathies of HIV-infected patients. PMID- 8345854 TI - Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus. AB - BACKGROUND: Central diabetes insipidus may be familial, secondary to hypothalamic or pituitary disorders, or idiopathic. Idiopathic central diabetes insipidus is characterized by selective hypofunction of the hypothalamic-neurohypophysial system, but its cause is unknown. METHODS: We studied 17 patients with idiopathic diabetes insipidus, in whom the duration of the disorder ranged from 2 months to 20 years. Only four patients had been treated with vasopressin before the study began. All the patients underwent endocrinologic studies and magnetic resonance imaging (MRI) with a 1.5-T superconducting unit, and two patients had biopsies of the neurohypophysis or the pituitary stalk. RESULTS: Nine of the 17 patients had thickening of the pituitary stalk, enlargement of the neurohypophysis, or both and lacked the hyperintense signal of the normal neurohypophysis. In the remaining eight patients, the pituitary stalk and the neurohypophysis were normal, although the hyperintense signal was absent. The abnormalities of thickening and enlargement were seen on MRI only in the patients who had had diabetes insipidus for less than two years, and the abnormalities disappeared during follow-up, suggesting a self-limited process. In addition to vasopressin deficiency, two patients had mild hyperprolactinemia and nine had impaired secretory responses of growth hormone to insulin-induced hypoglycemia. The two biopsies revealed chronic inflammation, with infiltration of lymphocytes (mainly T lymphocytes) and plasma cells. CONCLUSIONS: Diabetes insipidus can be caused by lymphocytic infundibuloneurohypophysitis, which can be detected by MRI. The natural course of the disorder is self-limited. PMID- 8345855 TI - Images in clinical medicine. Metastatic calcification of the shoulder in chronic renal failure. PMID- 8345856 TI - Thrombolysis in acute myocardial infarction. PMID- 8345857 TI - Clinical problem-solving. The sooner the better. PMID- 8345858 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 35-1993. A two-year-old boy with recurrent infections, cervical lymphadenopathy, and fever. PMID- 8345859 TI - Coronary thrombolysis--a perspective for the practicing physician. PMID- 8345860 TI - Problems in primary care. PMID- 8345861 TI - Problems in primary care. PMID- 8345862 TI - Problems in primary care. PMID- 8345863 TI - Problems in primary care. PMID- 8345864 TI - Problems in primary care. PMID- 8345865 TI - Problems in primary care. PMID- 8345866 TI - Problems in primary care. PMID- 8345867 TI - Problems in primary care. PMID- 8345868 TI - Problems in primary care. PMID- 8345869 TI - Problems in primary care. PMID- 8345870 TI - Shattuck Lecture--misconduct in medical research. PMID- 8345871 TI - Shattuck Lecture--misconduct in medical research. PMID- 8345872 TI - Shattuck Lecture--misconduct in medical research. PMID- 8345873 TI - Shattuck Lecture--misconduct in medical research. PMID- 8345874 TI - The medical treatment of open-angle glaucoma. PMID- 8345875 TI - If not nurses, who? If not now, when? PMID- 8345876 TI - An interview with Ellen Canepa Brzytwa and Scott Sutorius. Interview by Connie R Curran. AB - The Greater Cleveland Hospital Association Center for Health Careers Development analyzes health care manpower issues and implements action plans to assist its members with image, retention, recruitment, and other staff development initiatives. In this interview, Ellen Canepa Brzytwa and Scott Sutorius discuss their work with the Center for Health Careers Development, the nurse's presence at the decision table, and nursing leadership development. PMID- 8345877 TI - Effects of RN wages and non-wage income on the performance of the hospital RN labor market. AB - The complex hospital RN labor market is influenced by a number of intertwined and dynamic forces. Understanding how these pieces can be pulled together may improve the ability to anticipate changes in the RN labor market before they occur. PMID- 8345878 TI - Monitoring unit-based innovations: a process evaluation approach. AB - A comprehensive program evaluation helps assure that the program envisioned is implemented; or helps determine why it failed. It strengthens assumption about causality by clarifying the relationships between intervention and outcome. A program evaluation planning map can be helpful in measuring the extent of professional practice model implementation. PMID- 8345879 TI - Outcomes analysis: methods and issues. AB - Patient outcomes research provides an opportunity to improve the quality of patient care by modifying the structures and processes of care delivery. Optimal application of outcomes analysis involves collaboration between the health care disciplines. The result of such an endeavor would be the identification of health care practices that lead to desired patient outcomes in the most cost-effective manner. PMID- 8345880 TI - Discovering work excitement among navy nurses. AB - An interest in what makes work exciting among Navy Nurse Corps officers led to the use of Simms' work excitement data collection protocol in Navy Medical Centers. Significant levels of work excitement were found among Navy nurses when compared to civilian nurses in non-military settings. Overall, results indicated that Navy nurses are excited about the variety, the leadership/management experiences, and the opportunities for teaching and learning--elements that are the very essence of Navy nursing practice. PMID- 8345881 TI - Models of nursing care delivery and case management: clarification of terms. AB - Case management is a popular term used to describe a wide variety of nursing care programs in acute hospital and community settings. However, confusion exists about what programs and services compose case management, and how case management differs from nursing care delivery models. Defining nursing care delivery models and case management programs in acute-care and community settings, and identifying criteria for defining case management facilitates comprehension of program purposes and services. PMID- 8345882 TI - Addressing variations in nursing practice/technology through clinical practice guidelines methods. PMID- 8345883 TI - Risk management and the nurse manager: the role of patient-focused care. PMID- 8345885 TI - Options and opinions offered for financing health care reform. PMID- 8345884 TI - Diversified nursing practice in ambulatory care. AB - Expanding RN utilization in the ambulatory care setting provides numerous cost and patient care benefits during a time when health care costs are rising. Ambulatory care management personnel and physicians should analyze their present staffing and patient mix to determine if using a diversified nursing practice could benefit their practice. Nurses have been an integral part of the health care team since the 1800s. As the 21st Century quickly approaches, the role of the RN will be critical as ambulatory medicine attempts to improve patient satisfaction and patient access while continuing to provide quality care in a cost-effective manner. PMID- 8345886 TI - [Dilemmas in pediatric surgery]. PMID- 8345887 TI - [Folic acid for all fertile women?]. PMID- 8345888 TI - [Psychiatric disorders with use of simvastatin]. AB - Three patients are described with serious psychiatric complications related to use of simvastatin. The psychiatric symptoms concerned were mainly depression, anxiety and suicidal tendencies but also psychotic symptoms. The hypothesis is developed that in a particular population psychiatric (mood) disorders may be triggered by use of simvastatin or other cholesterol lowering compounds. A low or lowered cholesterol level may be related to disturbances in the cerebral serotonin metabolism. It may be necessary to be more alert for psychiatric (mood) disorders when a cholesterol lowering treatment (with simvastatin) is started and to stop it when psychiatric symptoms develop, or grow worse. PMID- 8345889 TI - [The return of serious infections caused by Streptococcus pyogenes]. PMID- 8345890 TI - [Measurement of body temperature]. PMID- 8345891 TI - [Degree of protection against poliomyelitis of Dutch subjects born before 1945 and of allochthonous subjects in Utrecht, and the relationship to socioeconomic status]. AB - In 1992 a seroepidemiological survey regarding the immune status for poliomyelitis was carried out amongst the population of the city of Utrecht: Dutch people born before 1945 and migrant workers and their families of all ages. Migrant workers and their families were well protected against poliomyelitis, using the WHO criteria (titre > or = I:8). The Dutch people born before 1945 were also well protected. Protection of Dutch people born before 1945 was better as their socioeconomic status was lower. PMID- 8345893 TI - [HIV-related non-Hodgkin lymphoma in 45 patients; a retrospective analysis]. AB - Non-Hodgkin lymphoma is seen in approximately 5% of patients with AIDS. In recent years, the incidence has increased due to an extension of the average lifespan of HIV-infected individuals. In this article we describe the histological and clinical features of 45 patients with HIV-related non-Hodgkin lymphoma seen at the Academic Medical Centre between 1984 and 1991. There were 43 men and 2 women with a median age of 40 years. Most patients had high-grade B-cell lymphoma; 85% had extranodal sites. Prognosis was poor: overall median survival was only 3.8 months. Twelve patients were treated with 3 or more courses of chemotherapy: their median survival was 8 months. In 7 of 12 patients a complete remission was obtained; their median survival was 18 months. A history of AIDS was a poor prognostic factor. PMID- 8345892 TI - [Surgical complications in treatment with continent ambulatory peritoneal dialysis; 9-year experience]. AB - OBJECTIVE: To determine the number of surgical complications in patients treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective (1980-1989), partially prospective (1987-1989). SETTING: Rijnstate Hospital, Arnhem, the Netherlands. METHOD: In 1978 CAPD was introduced in the Netherlands. Since 1980 we have used this technique in our clinic. Over the period 1980-1989 we studied the number of surgical complications of CAPD and the loss of catheter caused by these complications. With these numbers the probability of having a functioning Tenckhoff double cuff catheter was calculated with the Kaplan-Meier method. RESULTS: 101 patients (54 men (mean age 52.5 years), 47 women (mean age 49.6 years)) with terminal renal insufficiency were treated during the study period. 123 catheters were implanted of which 33 had to be removed afterwards. The probability of having a functioning catheter after one year was 85%, after two years 64% and after three years 53%. Peritonitis was the main cause of temporary or final loss of the catheter. The number of observed cases of peritonitis was 187. CONCLUSION: Methods to improve the survival of the catheter are prevention of peritonitis by using an appropriate system for the fluid exchanges, screening patients for the existence of diverticulosis before starting CAPD, and prevention of exit site and tunnel infections. PMID- 8345894 TI - [Leiomyosarcoma of the small intestine: a rare cause of gastrointestinal blood loss]. AB - A 61-year old man is described with recurrent gastrointestinal bleeding, due to a metastatic jejunal leiomyosarcoma. Because of the low incidence and the aspecific symptoms, a long delay occurred until the bleeding tumour and its metastases were demonstrated at radionuclide scanning and mesenteric angiography. The tumour bearing segment could be removed by simple surgical excision. PMID- 8345895 TI - [National study of the treatment of obstructive sleep apnea syndrome using uvulopalatopharyngoplasty or continuous positive pressure]. PMID- 8345896 TI - [Misconduct in biomedical research]. PMID- 8345897 TI - [Medical-ethical testing of family medicine research]. PMID- 8345898 TI - [Myth about the disadvantage of lowering of serum cholesterol level refuted]. PMID- 8345899 TI - [Myth about the disadvantage of lowering of serum cholesterol level refuted]. PMID- 8345900 TI - [AIDS and HIV-infection as occupational disease]. PMID- 8345901 TI - [AIDS and HIV-infection as occupational diseases]. PMID- 8345902 TI - Chronic spondylogenic cervical myelopathy. A critical evaluation of surgical treatment after early and long-term follow-up. AB - In the past, chronic spondylogenic cervical myelopathy has been thought of being a disease often resistant to neurosurgical therapy. 56 out of 70 patient treated by laminectomy or different ventral fusion procedures improved immediately following operation. Only 36, however, continued to be improved at follow-up 5 to 8 years later, whereas additional 8 had worsened again, and another 5 mean-while had died due to myelopathy. Laminectomy turned out to be the least successful procedure of treatment. Nevertheless, early diagnosis, early operation, appropriate and individual surgical procedures, careful re-evaluation at follow up, and -- if needed -- an early decision for a second-step operation can impressively improve the prognosis. PMID- 8345903 TI - Meningiomas of the tuberculum sella. AB - A series of 88 consecutive patients operated on for tuberculum sellae meningioma at the Neurosurgery Department of the University of Ankara Medical School was reviewed. Visual impairment was the most common initial complaint. All but 9 patients had visual symptoms. All patients underwent craniotomy, with an operating microscope being used in 62 cases. Use of the operating microscope appeared to increase the total removal rate while lowering the mortality. In our series visual function improved in 53.5%, was unchanged in 27.5%, and worsened in 19% of the patients. PMID- 8345904 TI - Percutaneous endoscopic lumbar discectomy (PELD). AB - Percutaneous endoscopic lumbar discectomy (PELD) is a new technique for the decompression of the lumbar disc space and removal of nucleus pulposus via a posterolateral approach. The technique was introduced in Germany by the authors in April 1987. The method is indicated in patients with nonsequestrated lumbar disc herniation with an intact dorsal longitudinal ligament. In local anesthesia, a working cannula (OD 5 mm) is placed at the dorsal lateral border of the disc. The disc space is opened with anulus trephines and the nucleus pulposus is removed with rigid and flexible forceps as well as with automated shaver systems under intermittent endoscopic control (discoscopy). The procedure is performed in local anesthesia. The results of the first thirty patients with a follow-up time between 6 months and 17 months could be graded as excellent in 13 cases, as good in 9 cases, as fair in 6 cases, and as bad in 2 cases. The relief of symptoms as judged by the patients was between 70-100 percent in the majority of the cases. Three patients had to be reoperated at the same level and site, because of either persistent or recurrent sciatica. The performance in local anesthesia, the atraumatic extraspinal approach, the reduced time of hospitalization and postoperative morbidity as well as the reduced time of work incapability are the main advantages of this new method. PMID- 8345905 TI - Aspiration or extirpation in cerebral abscess surgery? AB - The author carried out CT investigation of 11 patients who recovered after cerebral abscess operation. The finding established in all cases was a hypodensic area of various extensions, which, in 4 patients, made the impression of pseudocysts. Large pathologic lesions were found mainly in the patients in whom healing was complicated by relapse. Surprisingly, rather extensive pathologic changes in the patients were found which were cured by so-called "minimalized surgical intervention". The author imputes these changes to the remaining granulation tissue of the abscess capsula, which worsens conditions for healing. Aspiration is suitable mainly in cases in which the abscess is not -- or only slightly encapsulated. Preoperation CT scans cannot establish exactly the presence and eventual thickness of the capsula. The establishment relationship of the kind and extent of operation to the extent of later cerebral tissue changes in CT findings requires further observation and verification in a larger group of patients. PMID- 8345906 TI - The value of nuclear medicine for the diagnosis of spine diseases. AB - Nuclear medicine examinations hold an important position in the diagnosis of diseases of the spine. During the last decade, decisive progress has been made in the field of instrumentation and radiopharmaceutical techniques: the use of high resolution collimators and the introduction of emission computer tomography as examples of improved instrumentation as well as 99m-Technetium red blood cell labelling as a new radiopharmaceutical technique. These present some of the developments responsible for the growing importance of scintigraphical diagnosis. Inflammatory processes of the vertebrae and the surrounding soft tissues can be detected or excluded with high reliability by the use of radionuclide-labelled granulocytes. The important role of bone scintigraphy in the differential diagnosis of neoplastic bone disease relies on its high sensitivity combined with the quantitative analysis of increased bone metabolism. Furthermore, it provides exact information about the extent and a possible metastatic spread of bone tumours. In the field of orthopaedy and surgery, skeletal scintigraphy is of growing importance as a highly sensitive procedure in the detection of special traumatic lesions such as acute vertebral compression fractures and in the follow up of patients after bone surgical interventions. Despite the progress of other imaging modalities such as computer tomography and magnetic resonance imaging, nuclear medicine today is well-established in the assessment of diseases of the vertebral column. Among all scintigraphical diagnostic procedures, bone scintigraphy and the different techniques of inflammation imaging are of special importance. PMID- 8345907 TI - Surgical treatment of posterior fossa tumors in infancy and childhood: techniques and results. AB - In a collective of 72 children with tumors of the posterior fossa, the preoperative diagnosis, operation planning and performance, and use of additional procedures, like the preliminary ventricular drainage and interventriculostomy are described. The extent of intra- and postoperative complications is given. Postoperative lethality was 0% in the group operated on between 1979 and 1991. The responsible factors are discussed. The findings support the opinion of ALBRIGHT (1989) that the prognosis for such patients is most promising in the hands of a specialist in pediatric neurosurgery. PMID- 8345908 TI - The growth potential of ependymomas with varying grades of malignancy measured by the Ki-67 labelling index and mitotic index. AB - The prognostic significance of histopathological grade for postoperative outcome is not yet known for ependymomas. Data on proliferation kinetics of these tumors are few. In our study, the growth fraction was immunohistochemically determined by labelling cell nuclei with the monoclonal antibody Ki-67 in 24 tumors of the ependymoma group (2 malignant ependymomas grade III, 11 ependymomas grade II, 8 spinal ependymomas, and 3 subependymomas). The results were compared with the mitotic index in the same tumor areas. Both growth parameters are related to the grade of malignancy. The differences between the results of spinal ependymomas (grade I) and of intracranial tumors (grade II) were statistically significant. Malignant ependymomas had the highest values. Variable growth potentials could be demonstrated in a few tumors. A non-linear relationship between growth fraction and mitotic index was found, indicating a variable generation time in ependymomas (as in astrocytomas). Thus, with rising grade of malignancy the growth fraction increases and the generation time decreases. PMID- 8345909 TI - Physical exercise increases middle cerebral artery blood flow velocity. AB - The effect on the middle cerebral artery blood flow velocity (VMCA) of moderate and hard physical exercise on an ergometer cycle was examined in 10 healthy volunteers using transcranial Doppler sonography (TCD). During exercise, the heart rate increased by 136% and the systolic blood pressure by 37% (mean values). During initial moderate exercise, VMCA increased by 51%; in a following period of maximal physical work, VMCA decreased again by 20% in 9 of 10 volunteers although the heart rate continued to increase by 10% and the systolic blood pressure by 5% (mean values). Constriction of the MCA may explain the initial increase of VMCA, suggesting a role for large cerebral arteries in autoregulation. Our data indicate that the subsequent decrease of VMCA is caused by arteriolar constriction, a likely cause of which was hyperventilation during the excessive work period. PMID- 8345910 TI - Hypothalamic hamartoma: the role of surgery. AB - A hypothalamic hamartoma associated with true precocious puberty in a 7-month-old girl is hereby reported. Hormonal studies disclosed elevated serum levels of luteinizing hormone (LH) and follicle stimulating hormone, both of which responded well to LH-releasing hormone stimulation. Following a subtotal removal of the tumor, the clinical manifestations of precocious puberty as well as associated endocrinological abnormalities returned to normal. The role of surgery for this lesion, which appears to be safe when a planned microsurgical course is employed, is discussed. PMID- 8345911 TI - Encephalo-myo synangiosis (EMS) in the vertebrobasilar occlusive disease. Case reports. AB - Two cases of vertebro-basilar insufficiency treated with infratentorial (IT) Encephalo-Myo-Synangiosis (EMS) using the pedicled occipitalis muscle flap, are presented. IT EMS was carried out for revascularization of the vertebro-basilar system. None of these cases has suffered from either carotid or vertebro-basilar insufficiency during seven years follow-up period. As far as we know this is the first report of successful IT EMS for vertebro-basilar insufficiency. PMID- 8345913 TI - Implementation of an elective wellness course. AB - In an effort to increase knowledge and attitudes toward promoting health rather than treating disease, faculty in one school developed an elective wellness course open to all university students. The authors discuss how students learned concepts of wellness and developed individualized plans to improve their own health status. PMID- 8345912 TI - New aspects of neurotransplantation. AB - We have examined the possibility of promoting axonal regeneration within lesioned neural tissue using grafted artificial gel matrices. Polymeric matrices which feature a three-dimensional crosslinked macromolecular network were implanted into preformed lesions of the central nervous system (CNS). The host response consisted of matrix invasion by glial elements and the deposition of newly synthesized extracellular molecules. This rearrangement of the brain scarring process into an organized cellular coating promoted axonal regeneration into the gels. Entrapment of embryonic neurons and embryonal carcinoma (EC)-derived neurons, within the gels, was performed to explore the possibility of using polymer brain implants as neural graft microcarriers. Our results suggest that this approach will be useful for the delivery of cells and the promotion of axonal elongation required for successful neurotransplantation. PMID- 8345914 TI - The curriculum revolution: transforming barriers to education for registered nurses. AB - While designing an RN/BSN program, a small group of faculty accepted the challenge of the National League for Nursing (NLN) to initiate flexible, innovative learning experiences. Heeding the pleas of nursing leaders to engage in a curriculum revolution while incorporating the caution to maintain a balance within the curriculum, the group developed a nursing program that meets the current standards for NLN accreditation. PMID- 8345915 TI - A teaching strategy for identifying values: a clinical experience with the homeless. AB - Beginning baccalaureate students recorded their thoughts, feelings, and observations after participating in a clinical experience with the homeless. A content analysis protocol was used to uncover the meaning of the encounter. The findings suggest that assigning students to a homeless clinic is one way to help students identify professional values, such as altruism, equality, and human dignity. PMID- 8345916 TI - Managing adversity in the tenure and promotion process. AB - Faculty who meet tenure and promotion criteria may still be evaluated negatively at some point in the review process, perhaps by individuals who are unfamiliar with aspects of scholarship and teaching in the discipline of nursing. The author presents practical strategies that may succeed in turning over a negative decision. A prompt and aggressive course of action may prevent the need for an emotionally and financially draining lawsuit or grievance. PMID- 8345917 TI - Clinical memos: more than a communication tool. PMID- 8345918 TI - Faculty evaluation for professional growth. AB - This article tells the story of an attempt by one school of nursing to develop a system of faculty evaluation that nurtured professional growth. Recommendations for change in faculty evaluation practices were based on recognition of the need to develop a system of evaluation that was seen as less threatening and punitive and that encouraged self direction and participation in the evaluation process. Tools developed to evaluate teaching effectiveness were based on National League for Nursing outcome criteria, and were dependent on concept rather than context (i.e., classroom, clinical). PMID- 8345919 TI - Video taping return demonstrations. PMID- 8345920 TI - The public library as a clinical setting. PMID- 8345921 TI - An academic nursing center integrating education, role modeling, and research. PMID- 8345922 TI - Information literacy: educating for life-long learning. AB - Creating information-literate nurses is a challenging and complex task for nurse educators. It requires expertise on the part of the instructor, and a solid commitment to the importance of acquiring information skills and a willingness to demand quality work from the students. A librarian shares her views on information literacy. PMID- 8345923 TI - Student attitude toward computer-assisted instruction. PMID- 8345924 TI - A restructured nursing process model. AB - Nursing process has guided clinical nursing practice for more than 25 years. During this time, many changes have occurred in healthcare practices, delivery systems, and nursing. The cumulative effects of such changes show a need to restructure the basic nursing process model. The author presents a three-level differentiated nursing process model. PMID- 8345925 TI - Building on experiential learning in a leadership/management internship. PMID- 8345926 TI - Recommend changing answers on multiple choice examinations. PMID- 8345927 TI - The curriculum revolution within the constraints of academia. PMID- 8345928 TI - Mind the gap. PMID- 8345929 TI - Saudi women. PMID- 8345930 TI - What will PPS look like for FY 1994? PMID- 8345931 TI - Legal aspects--standards of care: Part II. PMID- 8345932 TI - Primary care: in legislation and in practice. PMID- 8345934 TI - Hospital redesign demands "open" information systems. PMID- 8345933 TI - Conscience and clinical care. PMID- 8345935 TI - Building a managed care approach. AB - Managed care enhances nursing autonomy and accountability and increases awareness of patients' interactions within a complex multidisciplinary healthcare delivery system. By using this approach, both physicians and nurses are able to assist patients to achieve outcomes quickly, decrease length of hospital stay, and facilitate continuity of care in a cost-effective manner. PMID- 8345936 TI - Making the commitment to managed care. AB - To develop and to implement managed care requires support from key participants including administrators, physicians, nurse managers and all healthcare providers. This multidisciplinary approach assures success and increases support when making the move toward managed care. PMID- 8345937 TI - Starting a hospital-based home health agency: Part I. The service and its environment. AB - Alternative care services and delivery options can improve quality, access and institutional viability. When properly implemented, home healthcare--an important link in the continuum of the healthcare delivery system--provides this service. Part I of this three-part series describes the research, review and beginning implementation, defines populations, and evaluates environmental assessments which set the foundation to establish a hospital-based agency. PMID- 8345938 TI - Depression among female registered nurses. AB - Depression, the most frequently diagnosed psychiatric illness, is characterized by feelings of sadness, pessimism, self-dislike and loss of energy, motivation and concentration. The relationship of self-esteem, assertiveness and anxiety to depression is studied in a group of female nurses. Recognizing predisposing factors in this high-risk group can begin a process to treat this illness. PMID- 8345939 TI - Costing the nursing service of patient education. AB - Patient Classification Systems (PCS) are one method of determining nursing service cost of patient education. A teaching classification study compares the value that different PCSs place on this aspect of nursing care. Through this comparison, information obtained helps nurses objectively update existing patient classification systems and provides guidelines for developing a system to include patient education. PMID- 8345940 TI - Decentralizing an overtime budget. AB - Decentralizing overtime costs moves this area of authority and accountability from central management to the unit level. Efficiency, quality and cost containment are addressed in the transition process. Together, nurse managers, staff and fiscal services discuss and plan alternatives to assure cost-effective resource allocation. PMID- 8345941 TI - Using market research for product line development. AB - A marketing research study determined patient needs and wants in order to tailor services within a family maternity care unit. In addition, an educational program, implemented in an effort to change the behavior of the caregivers in the clinical area, is described. PMID- 8345942 TI - From court to certification: establishing credibility. PMID- 8345943 TI - Staffing solutions: an in-house agency. AB - Cost-efficient, flexible labor and scheduling can be met within one's own organization through a professional staffing program. Conceptualization, implementation and evaluation of this in-house agency are detailed. In addition to meeting unit schedules, this program improved staff morale due to better coverage and compensation. PMID- 8345944 TI - Leadership: effects of birth order and education. AB - This study examines the dichotomy between female leadership qualities and those that traditionally link firstborn males and females to leadership positions. Research has repeatedly supported the belief that oldest children should rate higher than later born children on the California Psychological Inventory scales, but as this theoretical framework implies, these characteristics are inconsistent with the evolving leadership paradigm. PMID- 8345945 TI - On life and labels. PMID- 8345946 TI - My job as a staff nurse will change. PMID- 8345949 TI - Practice points. Issue: what qualifies me to administer intravenous chemotherapy? PMID- 8345947 TI - Nursing roles in advanced practice. The pilot project at Wright State University. PMID- 8345950 TI - In-utero diagnosis of Norrie disease by ultrasonography. AB - Obstetric ultrasonography of an obligate Norrie disease carrier revealed bilateral retinal detachments in a third trimester male fetus. Postnatal examination confirmed the diagnosis of Norrie disease. DNA linkage analysis with the markers L1.28 and MAO had been uninformative for this family. This report suggests that retinal detachment occurs late in the gestation of the affected fetus. PMID- 8345951 TI - Broad-spectrum Mobius syndrome associated with a 1;11 chromosome translocation. AB - The authors report a case of Mobius syndrome with Poland syndrome, cleft palate, dextrocardia, mandibular hypoplasia, and multiple areas of diffuse brain volume loss. Karyotype demonstrated a t(1;11)(p22;p13) translocation in the patient and his phenotypically normal father and brother. This case extends the spectrum of congenital disorders that are associated with Mobius syndrome and raises the possibility of genetic heterogeneity for the Mobius disorder. PMID- 8345953 TI - High symmetric anisometropia in monozygotic twins. AB - The first case in the literature of anisometropia of more than 20 dioptres in both left eyes of a pair of monozygotic 64-year-old twins is presented. The refractive parameters are given together with a short overview of the literature on anisometropia. PMID- 8345952 TI - Pigmented paravenous retinochoroidal atrophy (PPRCA) with optic disc drusen. AB - Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare retinal disorder which is diagnosed primarily on its typical funduscopic appearance of retinal pigment epithelial atrophy and clumping in a paravenous distribution. Pigmented paravenous retinochoroidal atrophy is usually asymptomatic and seldom causes marked decrease in visual acuity or significant impairment of electrophysiologic functions. Optic nerve head drusen, which are thought to be inherited as an autosomal dominant trait, rare in blacks, and known to be associated with retinitis pigmentosa, have not been previously reported with PPRCA. The authors present a case of PPRCA which is classic except for an additional finding of optic nerve head drusen. The heritability of PPRCA remains controversial but the authors' reported association of PPRCA and disc drusen seems to suggest some genetic influence. PMID- 8345954 TI - Retinoblastoma. Unusual warning and clinical signs. AB - Three clinical cases have been chosen to illustrate the pitfalls that can be encountered when warning signs other than leukokoria or strabismus indicate possible retinoblastoma. The first case, a four-year-old boy, was admitted to hospital after an accident, presenting uveitis, glaucoma and a subluxated lens. He was suffering from unilateral retinoblastoma, already exteriorized and the cause of death some months later. The second case, and 11-month-old female child was seen on fundus examination to present a yellowish elevated calcified mass which turned out to be tuberous sclerosis. The third patient, a 43-year-old male, father of two children suffering from retinoblastoma, was found on routine examination to be carrying a partially-calcified retinal tumour. Subsequent haemorrhaging rendered enucleation necessary and microscopic examination confirmed the diagnosis of retinoma. The diagnosis of retinoblastoma should always be kept in mind whenever an intraocular mass is revealed or where there are unexplained atypical ocular signs. PMID- 8345955 TI - An experience of the use of radioactive plaques after failure of external beam radiation in the treatment of retinoblastoma. AB - The authors have reviewed the results of radioactive plaques in recurrent retinoblastoma after external beam radiation in 34 eyes. They give their results on ocular conservation and on the visual outcome and compare these results with other series previously published. They think radioactive plaques are an alternative to enucleation in recurrent retinoblastoma after external beam. PMID- 8345956 TI - Cosmetic possibilities and problems in eyelid neurofibromas. AB - Neurofibromatosis type 1 (NF1) is an inherited systemic disease with frequent ocular involvement. A typical alteration observed in NF1 is the eyelid plexiform neurofibroma, often associated with facial homolateral hypertrophy. In such cases, surgical cosmetic results are rather unsatisfactory, since plexiform neurofibromas classically show a non-capsulated mass, with a marked tendency to local recurrence. The techniques for a cosmetic attempt are discussed on the basis of a personal series of eyelid reconstructions in NF1. The results can be considered satisfactory in some cases, when the orbital shape is preserved and the eyelid structure has not been excessively altered by the neurofibroma; in all other cases, the cosmetic outcome is inferior to the patient's and parents' expectations. The serious problem of recurrence is however a limitation to cosmetic surgery in eyelid neurofibromas. PMID- 8345957 TI - Optic atrophy in Marinesco-Sjogren syndrome: an additional ocular feature. Report of three cases in two families. AB - Marinesco-Sjogren syndrome (MSS) is a rare inherited disease with neurological and ocular manifestations. The latter include bilateral cataracts and, less frequently, nystagmus and strabismus. The authors report here three cases of MSS syndrome, all with optic atrophy, an additional ocular feature not hitherto described in this syndrome. PMID- 8345958 TI - Transthyretin-related TTR hereditary amyloidosis of the vitreous body. Clinical and molecular characterization in two Italian families. AB - Two unrelated Italian families affected by hereditary amyloidosis are described. Molecular genetic characterization demonstrated different mutations of the transthyretin gene. In all patients belonging to the TTR Ala 49 family the vitreous body, the heart and the peripheral nervous system were massively infiltrated by amyloid matter. In the TTR Pro 36 family vitreous opacities were the long-standing isolated manifestations of the disease. Two different patterns of vitreous deposits can be observed in these two families. The authors' data support the hypothesis that different pathological transthyretin proteins may have different affinity for the connective tissue in the vitreous. PMID- 8345959 TI - Development of vision in infants and young children. AB - Behavioral improvement in the quality of infant vision parallels neuroanatomic and neurophysiologic brain development. Progressive refinement of acuity can be tracked by means of tests that employ fixation and following, optokinetic nystagmus, preferential viewing, and pattern-evoked visual responses. These methods of evaluating vision in the preverbal child differ from each other in several respects; their relative advantages and disadvantages are discussed. PMID- 8345960 TI - Retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) remains a nonpreventable disorder associated with extreme prematurity. Recent advances in establishing the International Classification of ROP have facilitated both clinical care and research, highlighted by the demonstration of the effectiveness of cryoablative therapy for vision-threatening ROP. For those individuals who have ROP, early and life-long ophthalmic follow-up is critical. This is true for those with any residual retinal scars that we now know can lead to later vision loss as well as those who require services for the visually impaired. PMID- 8345961 TI - Ophthalmia neonatorum. AB - Ophthalmia neonatorum is the most common infection in the first month of life and can have serious systemic as well as ophthalmic morbidity. This article discusses the differential diagnosis and treatment of conjunctivitis in the neonate. Controversies in method of prophylaxis are reviewed. PMID- 8345962 TI - Amblyopia. Diagnosis and management. AB - Amblyopia is a difficult challenge for physicians caring for these children. If detected early with screening programs, the prognosis for successful treatment is greatly increased. If missed, the child may suffer from a lifetime of poor vision in one eye. Children who fail a visual screening test should be promptly referred to an ophthalmologist. Prompt detection and treatment of amblyopia secure a child the best chance for a good visual outcome. PMID- 8345963 TI - Diagnosis and treatment of strabismus disorders. AB - Strabismus is a common ocular abnormality in children and can have significant effects on visual, physical, and psychological development. The causes of ocular misalignment are numerous. Primary care physicians should be skilled in the evaluation of ocular motility in children. They also should understand the basic pathophysiology of common strabismus disorders and be able to identify those children at risk. This knowledge will aid in making a proper referral to an ophthalmologist when a strabismic disorder is suspected or detected. PMID- 8345964 TI - Common ocular signs and symptoms in childhood. AB - Children have many ocular complaints that generate a referral to the eye doctor. The complaints originate either from the child, the parents, the primary care physician, or teachers. This article describes the common complaints for which patients are referred and then how these problems should be addressed. PMID- 8345965 TI - Disorders of the lacrimal system apparatus. AB - Epiphora, or excess tearing, is a common problem in infants. The most frequent etiology of this disorder is a nasolacrimal duct obstruction. There are other conditions, however, some of which can be serious, which can cause tearing. Infections of the eyelids and conjunctiva, an undiscovered foreign body, and congenital glaucoma are among the conditions that must be ruled out when any child presents with excessive tearing. PMID- 8345966 TI - Common pediatric neuro-ophthalmologic conditions. AB - Neuro-ophthalmologic problems are some of the most distressing ocular conditions to affect children. In this article the author discusses the differential diagnosis and management of blindness during the first year of life. Nystagmus or 'jiggling eyes' tumors of the visual pathways and acquired ocular motor neuropathies comprise the balance of the article. PMID- 8345967 TI - The swollen and droopy eyelid. Signs of systemic disease. AB - Swollen and droopy eyelids are obvious ocular findings, unlike many ocular conditions that require the use of special equipment to observe. Neither of these findings is a specific diagnosis but rather each is evidence of localized disease and often is a sign of underlying systemic disorder. Therefore, it is important for the clinician evaluating the child with a swollen or droopy lid to have a working knowledge of these diagnostic possibilities. In this article the author presents the various causes of the swollen and droopy eyelid, focus on the most relevant clinical characteristics, and emphasize systemic associations. PMID- 8345968 TI - Ocular tumors of childhood. AB - It is important for the pediatrician to be aware of the benign and malignant ophthalmic tumors that can occur in children. This article covers some general concepts related to ocular tumors in children and briefly describes the clinical features and management of some of the more important tumors of the eyelids, conjunctiva, intraocular structures, and orbit. Although most ocular tumors in children are benign, certain malignant neoplasms can threaten the child's life as well as the child's sight. Hence, prompt recognition and patient referral to an ocular oncologist are crucial for proper clinical management. PMID- 8345969 TI - Eye injuries and prevention. AB - A disproportionate share of ocular and orbital injuries occur in children. This article reviews the evaluation and initial management of ocular trauma and chemical burns to the eye. Traumatic conditions are classified according to the particular area of the eye or orbit involved; chemical burns constitute a separate section. Sports-related injuries and their prevention are emphasized. PMID- 8345970 TI - Pediatric cataracts. AB - The presentation, etiology, diagnostic examination, and management of pediatric cataracts are discussed in this article. If untreated, cataracts result in significant visual deprivation. Evaluation of the pupillary light reflex should become an integral part of every pediatrician's physical examination. Patients should be referred for a complete eye examination whenever a cataract is suspected because early intervention may be the most important factor in determining a good visual outcome. PMID- 8345971 TI - Glaucoma in children. AB - Glaucoma in children is a relatively rare but frequently debilitating disorder. Pediatricians must be aware of the association of glaucoma with certain systemic diseases and congenital ocular abnormalities. Recognition of the signs of infantile glaucoma allows the physician to refer patients for definitive care. Timely therapy is critical to the successful management of children affected with glaucoma. PMID- 8345972 TI - The pediatrician's role in reading disorders. AB - This article summarizes clinically pertinent information on dyslexia and various disorders that contribute to school failure. Clinical, school, and research findings related to dyslexia are discussed. The role of the eyes, visual system, and controversial therapies are explored. The author emphasizes the role of the pediatrician as a team leader on the multidisciplinary approach to the diagnosis, therapy, and counseling of children with learning disabilities. PMID- 8345973 TI - Working with visually impaired children and their families. AB - This article contains basic information such as definitions and educational options for blind and partially sighted children. Specific suggestions for the pediatrician when working with these youngsters are included. Guidelines for parents to use when making educational decisions and when selecting adaptive technology are presented as well as a list of national organizations serving the visually impaired. PMID- 8345974 TI - Scientific literature on Ribavirin should be "objectively reviewed". PMID- 8345975 TI - Helping Down Syndrome children to reach new heights: the role of the pediatric nurse. PMID- 8345976 TI - Consensus: diagnosis and management of neurocysticercosis in children. PMID- 8345977 TI - Increased mortality after high titer measles vaccines: too much of a good thing. PMID- 8345978 TI - Antimicrobial treatment of occult bacteremia: a multicenter cooperative study. AB - This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8345979 TI - Occult blood and fecal leukocytes as screening tests in childhood infectious diarrhea: an old problem revisited. AB - During a 24-month period 446 children with diarrhea and 16 controls had examination of their stools for leukocytes and for occult blood. Fecal leukocytes were found in 36, 16 and 18% of children with Salmonella-Shigella-Campylobacter, rotavirus or enterotoxigenic Escherichia coli, or cryptosporidial diarrhea, respectively. Similarly 43, 39 and 38% of these groups, respectively, as well as 13% of controls had occult blood. Notably 70% of 10 Shigella cases had fecal leukocytes. In 166 children with mixed pathogens leukocytes were seen in 27 and 8% of children with Salmonella-Shigella-Campylobacter or noninvasive pathogen, respectively. Likewise 44 and 18% of these groups had occult blood. Agreement between both tests being positive was poor, the highest result being 50% for Shigella. Dysentery combined with both tests positive was associated with 15 (88%) cases of invasive agents present in stool cultures, and combination of dysentery with fecal leukocytes was associated with 21 (72%) cases of invasive agents recovered. The results of these tests should be interpreted in the context of the clinical situation. A combined clinical-epidemiologic and screening tests based approach to infectious diarrhea of childhood is suggested. PMID- 8345980 TI - Haemophilus influenzae type b carriage and immunity four years after receiving the Haemophilus influenzae oligosaccharide-CRM197 (HbOC) conjugate vaccine. AB - Late in 1991, before the implementation of a national immunization program against Haemophilus influenzae type b (Hib) in the United Kingdom, we performed a 4-year follow-up of 120 children who in 1987 had been enrolled in an immunogenicity trial in which 60 of them (vaccinees) received an Hib conjugate vaccine (HbOC) at the same time as diphtheria-tetanus toxoid-pertussis vaccine at the ages of 3, 5 and 9 months. Sixty others (controls) received only diphtheria tetanus toxoid-pertussis vaccine at the same ages and were not subsequently immunized against Hib. We investigated Hib pharyngeal colonization using the antiserum agar method and the concentrations of serum IgG antibody to the type b capsule by enzyme-linked immunosorbent assay. At 4 years of age the Hib colonization rates in vaccinees and controls were 8% (5 of 60) and 5% (3 of 60), respectively. The children colonized with Hib had greater serum anti-capsular IgG concentrations than did noncolonized children (P < 0.001), and colonized vaccinees tended to have higher concentrations than colonized controls (P = 0.053). Regardless of Hib colonization status vaccinees had greater antibody concentrations than controls (P < 0.001). Forty-nine percent of vaccinees had an antibody concentration > 1 microgram/ml. There was an inverse relationship between the Hib colony count on culture and the serum IgG concentration. These data indicate that the increase in serum antibody concentration after immunization with an Hib conjugate vaccine is sustained and that immunization primes for a booster response on exposure to Hib. There may be a relationship between previous Hib conjugate immunization and the density of Hib colonization in children. PMID- 8345982 TI - Clinical and laboratory diagnosis of pertussis in the regions of a large vaccine efficacy trial in Germany. AB - As a support service for a pertussis vaccine efficacy trial, a central diagnostic laboratory was established. Physicians in the geographic areas of the planned study were encouraged to send nasopharyngeal specimens from children and household contacts with cough illnesses whether or not the illnesses were typical of pertussis. From April, 1991, to February, 1992, 3629 specimens were received and in 601 instances (16.6%) Bordetella pertussis was isolated. Only 3.3% of patients with positive cultures had received pertussis vaccine whereas 16.1% of culture-negative patients had received vaccine (P < 0.0001). Fever was more common (12.2%) in patients with negative cultures compared with those with positive cultures (5.4%) (P < 0.0001). B. pertussis isolation rates fell markedly after 21 days of cough. Significantly more patients with negative cultures compared with those with positive cultures had been treated with erythromycin (8.5 vs. 2.9%; P < 0.0001). Patients with cough for greater than 4 weeks and specimen collection within 2 weeks of cough onset had a B. pertussis isolation rate of 59%. Similarly if whoop occurred under the same circumstances the isolation rate was 80%. In this study 25.5% of patients with culture confirmed pertussis had illnesses with cough of less than 21 days duration. This finding suggests to us that a pertussis case definition in efficacy trials that requires cough of 21 days is excessively restrictive. PMID- 8345981 TI - Comparative immunogenicity of four Haemophilus influenzae type b conjugate vaccines in Alaska Native infants. AB - We compared the immunogenicity of the four available Haemophilus influenzae type b (Hib) conjugate vaccines in Alaska Native infants. Three of the vaccines, Hib oligosaccharide-CRM197 (HbOC), polyribosylribitol phosphate-diphtheria toxoid (PRP-D) and polyribosylribitol phosphate-tetanus toxoid (PRP-T), were given at 2, 4 and 6 months of age, and the PRP Neisseria meningitidis outer membrane protein (PRP-OMP) conjugate vaccine was given at 2 and 4 months of age. Enrollment was largely sequential by vaccine availability beginning with HbOC and ending with PRP-T. A total of 225 infants completed the full vaccination series. Groups of infants receiving the different vaccines did not differ significantly by sex, ethnicity, degree Alaska Native or age at vaccination. The only vaccine that induced a response with the first 2-month dose was PRP-OMP; 91% of infants had > or = 0.15 micrograms/ml and 57% had > or = 1.0 microgram/ml of anti-PRP antibody by 4 months of age. After two doses it also remained the most immunogenic. After the full three vaccine series, trials that requires cough of 21 days is excessively restrictive. PMID- 8345983 TI - Efficacy of plasmin-treated intravenous gamma-globulin for therapy of Kawasaki syndrome. AB - In order to delineate the efficacy of plasmin-treated intravenous gamma-globulin (IVGG) in the treatment of Kawasaki syndrome, we compared the frequency of coronary artery abnormalities in children treated or not with IVGG for Kawasaki syndrome. Among 291 cases of Kawasaki syndrome diagnosed during the period of 1987 to 1991 without coronary abnormalities within 10 days of the onset of illness, 128 were treated with IVGG and aspirin and were compared with 163 treated with aspirin alone. IVGG was given in a dosage of 400 mg/kg/day for 4 consecutive days. The detection of coronary abnormalities was monitored by two dimensional echocardiography. Two weeks after enrollment coronary artery abnormalities were present in 37 (22.7%) of 163 children in the aspirin group and in 9 (9%) of 128 in the gamma-globulin group (P < 0.05). Seven weeks after enrollment, abnormalities were present in 20 (12.3%) of 163 children in the aspirin group and in 6 (4.6%) of 128 in the IVGG group (P < 0.05). We conclude that plasmin-treated IVGG is effective in reducing the prevalence of coronary artery abnormalities in Kawasaki syndrome and suggest a predominant role of the Fc gamma fragment of IgG in the therapeutic effect. PMID- 8345984 TI - International childhood vaccine initiative. PMID- 8345985 TI - Hydrocephalus complicating lymphocytic choriomeningitis virus infection. PMID- 8345986 TI - Infections caused by beta-lactamase-producing Fusobacterium spp. in children. PMID- 8345987 TI - Recurrent hydatid disease after therapy with albendazole. PMID- 8345988 TI - Corynebacterium xerosis ventriculoperitoneal shunt infection in an infant: report of a case and review of the literature. PMID- 8345989 TI - Diphtheria presenting as abdominal pain and arthralgia. PMID- 8345990 TI - Pyosalpinx caused by Streptococcus pneumoniae in a young girl. PMID- 8345991 TI - Kingella kingae osteomyelitis of the calcaneus in young children. PMID- 8345992 TI - Persistent coccobacillary sepsis in a preterm newborn. PMID- 8345993 TI - Cefixime therapy for otitis media. PMID- 8345994 TI - Significance of abnormal liver function tests associated with administration of amoxicillin and other penicillins. PMID- 8345995 TI - Intravenous immunoglobulin use in the neonate: role in prophylaxis and therapy of infection. PMID- 8345996 TI - Failure of tracheal aspirate cultures to define the cause of respiratory deteriorations in neonates. AB - The spectrum of organisms responsible for lower respiratory tract infection in chronically ventilated neonates is poorly defined. During an 18-month period 63 infants with a respiratory deterioration defined as an increase in fractional inspired O2 concentration > or = 20% and/or mean airway pressure > or = 3 cm H2O were evaluated for pulmonary infection. These infants were compared with 58 stable control ventilated infants. Tracheal aspirates for culture and Gram stain were taken from both groups and were cultured for bacteria, viruses, Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis. In addition each infant had complete blood counts with differential and chest roentgenograms evaluated. Positive tracheal aspirates defined as a heavy growth of a single or two bacterial organisms, and/or any growth of virus, Chlamydia and U. urealyticum were found in 23 of 63 study patients and 20 of 58 controls (P > 0.05). The most frequent isolate in both groups was U. urealyticum. Chest radiographs were positive (new changes, particularly atelectasis and infiltrates) more frequently in the study group than in controls, but complete blood count and tracheal aspirate Gram-stained smears were not helpful in discerning colonization from infection. We conclude that positive tracheal aspirates occur with equal frequency among infants with a clinical suspicion of lower respiratory tract infection and in "well" controls. Chest roentgenogram may be a useful adjunctive test to discriminate between colonization and lower respiratory tract infection. PMID- 8345997 TI - Outbreak of early onset group B streptococcal sepsis. AB - During January and August, 1990, 23 cases of early onset Group B Streptococcus (GBS) disease occurred in a Kansas City, MO, hospital with an attack rate of 14/1000 live births, compared with an annual rate of 1.2 cases/1000 live births for 1988 through 1989. Case infants were compared with controls matched by birth weight, race, maternal age and day of delivery and to a second group of infants of mothers colonized with GBS to identify risk factors and consider intervention strategies during the outbreak. The presence of multiple serotypes among the invasive strains suggested that the outbreak was not caused by a common source. Case mothers were more likely than control mothers to have chorioamnionitis, intrapartum fever or rupture of membranes > 12 hours, and premature case infants were more likely to have a history of rupture of membranes before onset of labor. Multiparous mothers of case infants were more likely to have a history of spontaneous abortion (odds ratio, 6.7; 95% confidence interval, 1.0 to 45.9). No single factor could explain the increase in GBS disease. If intrapartum antibiotic prophylaxis had been used for selected GBS carriers based on presence of either rupture of membranes > 12 hours, intrapartum maternal fever or preterm labor, 7.4% of all deliveries would have received antibiotics and 73% of cases could potentially have been prevented. We conclude that identification of colonized mothers with perinatal risk factors and use of intrapartum antibiotics could be expected to prevent substantial disease during an outbreak of early onset GBS disease. PMID- 8345998 TI - Mycoplasma hominis and Ureaplasma urealyticum in neonates with suspected infection. AB - The role of genital mycoplasmas in the pathogenesis of neonatal infection is incompletely understood. We performed nasopharyngeal, blood and cerebrospinal fluid (CSF) cultures for Mycoplasma hominis and Ureaplasma urealyticum in 69 neonates who underwent a diagnostic workup for suspected sepsis. The mean gestational age was 35.9 weeks (range, 25 to 42 weeks) with a mean birth weight of 2386 g (range, 652 to 4420 g). Twenty-seven infants (39.1%) had positive nasopharyngeal cultures; 6 were positive for M. hominis, 10 for U. urealyticum and 11 for both organisms. Seven (26%) of these 27 patients developed chronic lung disease compared with 2 (4.7%) infants in the non-colonized group. Nine infants had positive CSF cultures for M. hominis and one infant had a positive CSF culture for U. urealyticum. All blood cultures were sterile. One of the infants with a positive CSF culture for M. hominis had clinical evidence of systemic infection. All of the infants were treated with antibiotic agents that were not active against mycoplasmas. These data indicate that genital mycoplasmas can be found commonly in the CSF and nasopharynx of infants with suspected sepsis. Their etiologic role in the causation of infection and chronic lung disease, however, remains unclear. PMID- 8345999 TI - Risk factors associated with fungal peritonitis in very low birth weight neonates with severe necrotizing enterocolitis: a case-control study. AB - Fungal peritonitis is uncommon in infants with severe necrotizing enterocolitis with intestinal perforation. In our institution we noted a significant (P < 0.01) increase in fungal peritonitis from 7% (3 of 45 cases of peritonitis) from January, 1980, to June, 1989, to 35% (8 of 23 cases of peritonitis) from July, 1989, to December, 1991. The mean birth weight of 11 infants with fungal peritonitis (946 +/- 70 g) (mean +/- SE) was significantly less (P = 0.008) than that of 57 infants with bacterial peritonitis (1282 +/- 52 g). In a case-control study to identify risk factors associated with fungal peritonitis, 11 infants with bacterial peritonitis were matched to the 11 infants with fungal peritonitis by age at bowel perforation and birth weight. Infants with fungal compared with bacterial peritonitis had significantly longer (P < 0.05): median duration of umbilical vessel catheterization before bowel perforation, 10 vs. 3 days, respectively; median duration of antibiotic therapy before bowel perforation, 23 vs. 14 days, respectively; and median duration of intubation, 13 vs. 5 days, respectively. Other potential risk factors that were not significant in this study included duration of central venous catheterization, total parenteral nutrition, intravenous lipid administration, aminoglycoside use, dexamethasone use or methyl xanthine therapy. In summary fungal peritonitis in neonates with necrotizing enteritis was significantly related to extremely low birth weight, prolonged umbilical vessel catheterization, prolonged exposure to antibiotics and prolonged intubation. PMID- 8346001 TI - Inactivation of respiratory syncytial virus by detergents and disinfectants. AB - The activity of a number of detergents and disinfectants against respiratory syncytial virus (RSV) was evaluated in an in vitro assay system. Equal volumes of RSV and serial 10-fold dilutions of the test agents were mixed at 4 degrees C for 5 minutes. The RSV titer in each mixture was compared with that of untreated RSV alone. In 14 experiments with input RSV titers ranging from 2.6 x 10(3) to 2 x 10(7) plaque-forming units/ml, a 10-fold dilution of 5.25% sodium hypochlorite (generic bleach) inactivated (> or = 3-log reduction in titer) the virus. With lower RSV titers inactivation was also observed at a 100-fold dilution of bleach. Fetal calf serum concentrations up to 50% as an organic load did not diminish the bleach effect. The degree of RSV inactivation was also defined for Lysol, povidone-iodine, Amphyl, Hibiclens, Osyl, ethanol and Listermint. The short contact time, the reproducible nature of the findings and the continued effectiveness with increasing organic loads all suggest that detergents and disinfectants can potentially play an important role in decreasing the spread of RSV infection. PMID- 8346000 TI - Cimetidine as an immunomodulator in subacute sclerosing panencephalitis: a double blind, placebo-controlled study. AB - Cimetidine, an H2 histamine receptor antagonist, was used in subacute sclerosing panencephalitis patients for its immunomodulatory effect. Patients were randomly assigned to cimetidine (n = 7) and placebo (n = 7) groups. Neurologic disability index, lymphocyte functions, cerebrospinal fluid measles antibodies and IgG index were evaluated before and after 2 months of treatment. The neurologic disability index of the cimetidine group remained stable during the study period whereas the placebo group worsened. There were no differences in the immunologic test results, cerebrospinal fluid measles antibody titers and IgG index of the two groups. This study suggests that cimetidine may have a favorable effect on the clinical progression of subacute sclerosing panencephalitis. Further studies are required to investigate its mechanism of action and the associated changes in immune status. PMID- 8346002 TI - Microalbuminuria: an index of severity in childhood meningitis. AB - Urinary albumin excretion (AE) was determined by a sensitive method (below dipstick positive values, 15 to 300 micrograms/minute) in 68 children with meningitis during 48 hours after hospital admission; 51 children had bacterial meningitis (BM) and 17 had aseptic meningitis. AE (results as mean +/- SD) during 0 to 24 hours was higher (P < 0.001) in patients with BM (36 +/- 40 micrograms/minute) than with aseptic meningitis (7 +/- 5 micrograms/minute), albeit no cutoff value distinguished the two conditions accurately. In BM the clinical course (uneventful, intermediate, complicated, fatal) correlated with AE of 0 to 24 hours (r = 0.34, P < 0.05) and AE of 25 to 48 hours (r = 0.63, P < 0.001). Cerebrospinal fluid protein concentration 24 to 36 hours after initiation of treatment correlated with AE of 25 to 48 hours (r = 0.34, P < 0.05). An index obtained by dividing AE by the weight of the child predicted the severity of clinical course more precisely (77% sensitivity, 85% specificity) than AE alone. Hence renal AE is an easily and non-invasively determined acute phase reactant of potential value as an early estimate of severity of BM. PMID- 8346003 TI - Carriage of Haemophilus influenzae type b in children after widespread vaccination with conjugate Haemophilus influenzae type b vaccines. AB - Rates of invasive Haemophilus influenzae type b (Hib) disease in children decreased very rapidly after licensure of Hib conjugate vaccines. A role for a vaccine-related reduction in nasopharyngeal carriage of Hib has been suggested. We studied oropharyngeal carriage of Hib and vaccination rates in a population of 2- to 5-year-old children in metropolitan Atlanta. Among 584 children 75% were vaccinated with an Hib conjugate vaccine, 17% had not been vaccinated and 8% had no vaccination records available. Forty-one percent of the children were colonized with H. influenzae. One child was colonized with Hib. Hib carriage (0.17%; upper 95% confidence interval boundary, 0.97%) was substantially lower than the estimates of Hib carriage from prior studies of children who had not received Hib conjugate vaccines. Our data are consistent with a decline in Hib carriage induced by widespread use of conjugate Hib vaccines, which may have contributed to the decline of Hib disease in United States children. PMID- 8346004 TI - Vaccination with Haemophilus influenzae type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage of Haemophilus influenzae type b among American Indian children. AB - The effect of Haemophilus influenzae type b (Hib) meningococcal protein conjugate vaccine (Hib-OMPC; Merck, Sharp & Dohme) on oropharyngeal (OP) carriage of Hib was evaluated in Navajo and Apache Indian children, who are known to be at high risk for invasive Hib disease. We obtained 1423 OP swabs at well child visits from 1321 children 3 months to 4 years of age: 293 of the swabs were obtained from children before the administration of any Hib-OMPC; 1119 were taken after the primary vaccination series; and 11 after the booster dose. Swabs were tested for the presence of Hib capsular polysaccharide antigen by enzyme-linked immunosorbent assay. Forty of 1423 swabs were positive for Hib. Among the 40 positive swabs 5 (13%) were obtained from children who had received Hib-OMPC vaccine appropriate for age at swabbing, compared with 500 of 1383 (36%) of negative swabs. Children who were OP carriers of Hib were older than noncarriers (mean age, 13 and 9 months, respectively) and a greater proportion of carriers (48%) had symptoms of respiratory infection at the time of swabbing than noncarriers (30%). These variables were significantly related to increased risk of OP carriage of Hib when incorporated jointly in a logistic regression model: not vaccinated according to age (odds ratio 2.7, 95% confidence interval 1.00 to 7.05); increase of age in months (odds ratio 1.1, 95% confidence interval 1.02 1.10); and respiratory infection symptoms present (odds ratio 2.0, 95% confidence interval 1.06-3.77). Thus besides preventing invasive Hib disease, appropriate vaccination with Hib-OMPC appears to reduce OP carriage of Hib. PMID- 8346006 TI - Antibacterial activity of garlic and onions: a historical perspective. PMID- 8346005 TI - Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation. AB - Twenty asthmatic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR 125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients, 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza. PMID- 8346007 TI - False positive latex agglutination test in cerebrospinal fluid after immunization for Haemophilus influenzae type b. PMID- 8346008 TI - Mycobacterium avium complex parotid lymphadenitis: successful therapy with clarithromycin and ethambutol. PMID- 8346009 TI - Mycobacterium chelonae causing recurrent neck abscess. PMID- 8346010 TI - Acute supraglottitis caused by varicella. PMID- 8346011 TI - Hepatitis B virus infection in children with cancer. PMID- 8346013 TI - Tuberculin skin tests: why the Mantoux? PMID- 8346012 TI - Cost of congenital syphilis. PMID- 8346014 TI - A role in DNA binding for the linker sequences of the first three zinc fingers of TFIIIA. AB - Zinc fingers of the TFIIIA type are connected by short linker sequences between the structural units. Structural investigations by 2D NMR in solution and by X ray crystallographic analyses of complexes with DNA point to a passive role for the linkers. We have therefore investigated the influence of the linker sequence on DNA binding using as a model the first three fingers of the protein TFIIIA. Insertion of certain heterologous linkers abolishes binding, and replacement of individual amino acids can reduce binding by factors of up to twenty-four. PMID- 8346015 TI - Cytoskeletal reorganization and TPA differently modify AP-1 to induce the urokinase-type plasminogen activator gene in LLC-PK1 cells. AB - Urokinase-type plasminogen activator (uPA) is an extracellular protease and expressed in various cells that exhibit dynamic changes in cell morphology, suggesting a link between cytoskeletal reorganization (CSR) and uPA expression. CSR can be induced by pharmacological agents, such as by colchicine for microtubule cytoskeleton and by cytochalasin for microfilament cytoskeleton. Using these agents, we previously showed that CSR induced the uPA gene in LLC-PK1 cells independently of the protein kinase C and cAMP-dependent protein kinase. Here we show that the induction of the uPA gene by CSR is mediated by the activation of c-Jun which interacts with an AP-1-like site located 2 kb upstream of the uPA gene. 12-O-tetradecanoylphorbol 13-acetate (TPA) induces the uPA gene through the same elements, but additionally utilizes an adjacent PEA3 element and induces c-fos. Furthermore, CSR induces a greater accumulation and a more pronounced phosphorylation of c-Jun than TPA induction. AP-1 is a positive regulator of growth and oncogenesis, and CSR is an integral part of these processes. Our results provide a view how CSR and AP-1 could be coupled in these processes. We also show that TPA and CSR act synergistically, suggesting a model where an initial activation signal could be amplified by CSR. PMID- 8346016 TI - Identification of amino acids in HIV-2 integrase involved in site-specific hydrolysis and alcoholysis of viral DNA termini. AB - The human immunodeficiency virus integrase (HIV IN) protein cleaves two nucleotides off the 3' end of viral DNA and subsequently integrates the viral DNA into target DNA. IN exposes a specific phosphodiester bond near the viral DNA end to nucleophilic attack by water or other nucleophiles, such as glycerol or the 3' hydroxyl group of the viral DNA molecule itself. Wild-type IN has a preference for water as the nucleophile; we here describe a class of IN mutants that preferentially use the 3' hydroxyl group of viral DNA as nucleophile. The amino acids that are altered in this class of mutants map near the putative active-site residues Asp-116 and Glu-152. These results support a model in which multiple amino acid side-chains are involved in presentation of the (soluble) nucleophile. IN is probably active as an oligomeric complex, in which the subunits have non equivalent roles; we here report that nucleophile selection is determined by the subunit that supplies the active site. PMID- 8346017 TI - Genome sequencing on both strands: the Janus strategy. AB - The design of large scale DNA sequencing projects such as genome analysis demands a new approach to sequencing strategy, since neither a purely random nor a purely directed method is satisfactory. We have developed a strategy that combines these two methods in a way that preserves the advantages of both while avoiding their particular limitations. Computer simulations showed that a specific balance of random and directed sequencing was required for the most efficient strategy, termed the Janus strategy, which has been used in the Escherichia coli genome sequencing project. This approach depended on obtaining sequence easily from either strand of a cloned insert, and was facilitated by inversion of the insert in the engineered M13 vector Janus, by site-specific recombination. The inversion was accomplished simply by growth on the appropriate host strain, when the DNA strand incorporated into the new single stranded phage was complementary to that in the original phage, and was sequenced by the same simple protocol as the first strand. PMID- 8346018 TI - Analysis of the Escherichia coli genome. III. DNA sequence of the region from 87.2 to 89.2 minutes. AB - The DNA sequence of 96.5 kilobases of the Escherichia coli K-12 genome has been determined, spanning the region between rrnA at 87.2 minutes and katG at 89.2 minutes on the genetic map. The sequence includes 84 open reading frames, of which 46 code for unidentified proteins. Six previously mapped but unsequenced genes have been identified in this span: mob, fdhD, rhaD, rhaA, rhaB, and kdgT. In addition, five new genes have been assigned: the heat shock genes hsIU and hsIV, and the genes fdoG, fdoH, and fdoI, which encode the three subunits of formate dehydrogenase-O. The arrangement of the genes relative to possible promoters and terminators suggests 57 potential transcription units. Other features include the precise location of the bacteriophage P2 attachment site attP2II, and eleven REP elements, including one containing 9 REP sequences--one of the largest such elements known. This segment brings the total length of contiguous finished sequence to 325 kilobases. PMID- 8346019 TI - Purification of a HeLa cell nuclear protein that binds selectively to DNA irradiated with ultra-violet light. AB - Ultraviolet (UV) light induces a variety of lesions in DNA of which the pyrimidine dimer represents the major species. Pyrimidine dimers exist as both a cyclobutane type and a 6-4' (pyrimidine-2'-one) photoproduct. We have purified a protein of M(r) approximately 125,000 from HeLa cell nuclei which binds efficiently to double-stranded DNA irradiated with UV light but not to undamaged DNA. This protein was designated UVBP1 (UV damage binding protein 1). UVBP1 did not recognise DNA damaged by cisplatin. Using oligonucleotides with a single dipyrimidine site for induction of UV photoproducts, binding of UVBP1 to a TC containing substrate was shown to be more efficient than to substrates containing a TT, a CT or a CC pair. This binding specificity implies selective recognition of the 6-4' photoproduct. Further evidence for this was provided by the finding that hot alkali treatment of the substrate (which selectively hydrolyses 6-4' photoproducts) abrogated binding of UVBP1, whereas incubation with DNA photolyase to remove cyclobutane dimers did not. No detectable DNA helicase, ATPase or exonuclease activity was associated with the purified protein. We suggest that UVBP1 may be involved in the lesion recognition step of DNA excision repair and could contribute to the preferential repair of 6-4' photoproducts from the DNA of UV-irradiated mammalian cells. PMID- 8346021 TI - Direct selection of DNA sequences conserved between species. AB - An essential requirement in the analysis of genomes is the identification of functionally important sequence elements, which are often evolutionarily conserved. We describe here the development of a novel procedure for the selective isolation of conserved sequences which is based on hybridization of PCR amplifiable DNA fragments from the whole genome of one species to biotinylated DNA from a genomic region of another species. The interspecies DNA hybrids are immobilized and the PCR-amplifiable DNA fragments are eluted, amplified and after further hybridization-amplification rounds cloned. This method was used for the generation of sublibraries of conserved sequences from mouse and pig DNA from regions corresponding to cosmids from the human Xq28 region. Mouse and pig homologs of sequences containing exons of known human genes, as well as exons from novel genes have been identified. PMID- 8346020 TI - The Kluyveromyces gene encoding the general transcription factor IIB: structural analysis and expression in Saccharomyces cerevisiae. AB - The Kluyveromyces lactis gene encoding the general transcription factor IIB (TFIIB) was isolated from a genomic library by complementation of the cold sensitive phenotype conferred by a mutation in the SUA7 gene, which encodes TFIIB in Saccharomyces cerevisiae. DNA sequence analysis of the KI-SUA7 gene revealed a 357 amino acid open reading frame that is 67% identical (81% overall similarity) to S. cerevisiae TFIIB. Comparison with other eukaryotic TFIIBs indicated that the most highly conserved sequence is located adjacent to the Zn-finger motif near the N-terminus. A plasmid shuffle system was used to replace the essential Sc-SUA7 gene with KI-SUA7 in S.cerevisiae. The resulting strain was viable and phenotypically indistinguishable from the normal strain. However, transcription start site selection at the ADH1 locus, shown previously to be affected by mutations in Sc-SUA7, was affected by K.lactis TFIIB. This result provides further evidence that TFIIB is a principal determinant of start site selection in yeast. PMID- 8346022 TI - Solution structure of a DNA-binding domain from HMG1. AB - We have determined the tertiary structure of box 2 from hamster HMG1 using bacterial expression and 3D NMR. The all alpha-helical fold is in the form of a V shaped arrowhead with helices along two edges and one rather flat face. This architecture is not related to any of the known DNA binding motifs. Inspection of the fold shows that the majority of conserved residue positions in the HMG box family are those involved in maintaining the tertiary structure and thus all homologous HMG boxes probably have essentially the same fold. Knowledge of the tertiary structure permits an interpretation of the mutations in HMG boxes known to abrogate DNA binding and suggests a mode of interaction with bent and 4-way junction DNA. PMID- 8346023 TI - Uracil-DNA glycosylase as a probe for protein--DNA interactions. AB - The DNA repair enzyme Uracil-DNA Glycosylase (UDG) can be used to investigate three different features of protein-DNA interactions. Complexes can be probed by simple protection experiments ('footprinting') or by two kinds of interference assays: a missing thymine site (MT-site) experiment and a missing thymine methyl site (MTM-site) experiment. The three probing methods are assessed using the well characterized in vitro systems of lambda repressor and lac repressor binding to their respective operator sites. The results obtained with UDG probing agree well with previous probing experiments on the same systems and, in certain cases, extend previous interpretations: for example, comparison of the results obtained with the two interference assays shows that formation of the lac repressor operator complex requires interactions with the methyl group of one particular thymine residue (T-13) in the operator but also requires interactions with other parts of the thymine base at operator positions 7, 8, 9, 21, 23 and 24. Overall, the properties of UDG recommend it as a versatile and convenient method to investigate DNA-protein interactions both in vitro and possibly in vivo. PMID- 8346024 TI - Microtiter format gene quantification by covalent capture of competitive PCR products: application to HIV-1 detection. AB - We have developed a simple gene quantification system using the competitive polymerase chain reaction (CPCR) followed by microtiter format analysis. CPCR is carried out using a mutant competitor with the same size as the target DNA product, and a minimal base exchange to insure the same amplification kinetics. One primer is aminated at the 5' end to produce PCR products that are captured onto carboxylated wells of microtiter plates through peptide bond formation. The non-aminated DNA strands are stripped off from the wells by alkali washing, and the remaining aminated strands are hybridized with either a digoxigenin-labeled wild type-specific oligonucleotide probe or a competitor-specific probe. To standardize the hybridization conditions of the probes, a DNA construct containing wild type and mutant competitor sequences in tandem is captured at different concentrations, hybridized with the probes, and used to generate a standard curve. Bound probes are detected by anti-digoxigenin antibody conjugated with peroxidase and chromogen. Optical densities are recorded with a conventional microtiter plate reader and converted to concentrations according to the standard curves. The ratios of wild type DNA to mutant competitor are used to determine the initial amounts of wild type DNA in the samples. This method was used successfully to quantify human immunodeficiency virus type 1 (HIV-1) env gene in human lymphocytes. It only requires a thermal cycler and a conventional microtiter plate reader, and can be readily done on a large scale. Potential applications include detection of other pathogens, diagnosis of genetic disorders and studies of gene expression. PMID- 8346025 TI - MGM101, a nuclear gene involved in maintenance of the mitochondrial genome in Saccharomyces cerevisiae. AB - A nuclear mutation, mgm101, results in temperature sensitive loss of mitochondrial DNA (mtDNA) in the yeast Saccharomyces cerevisiae. The corresponding gene, MGM101, was isolated from a genomic DNA library by complementation. Sequence analysis shows that MGM101 encodes a positively charged protein of 269 amino acids with a calculated molecular weight of 30 kDa. This analysis also reveals that MGM101 is adjacent to the ribosomal protein gene RPS7A on chromosome X and hybridization indicates it occurs in single copy. Creation of a null mutant by targeted disruption showed that the gene has no essential cellular function, aside from its participation in mitochondrial genome maintenance. As no counterpart has been identified in databases it is a novel protein whose role has yet to be determined. Expression of MGM101 is low on glucose medium but on galactose there is a two-fold increase in the level of the transcript. PMID- 8346026 TI - The ets multigene family is conserved throughout the Metazoa. AB - This study provides the first empirical evidence for the conservation of the ets proto-oncogene transcription factor family throughout the Metazoa. Using the polymerase chain reaction with degenerate primers corresponding to conserved sequences within the ETS DNA-binding domain, we have detected ets genes in a range of lower metazoans, including sponges, ctenophores, anemones, flatworms and nematodes, and in several higher invertebrate metazoans. Many of these sequences are significantly divergent from the original v-ets-1 oncogene, although most can be aligned with recently defined groups within the ets gene family. Multiple ETS domain sequences were detected in a number of the lower metazoan species, providing evidence for the existence of an ets multigene family at the earliest stages of metazoan evolution. In contrast, we were unable to detect any ETS sequences in fungal, plant or several protozoan DNAs. Our findings suggest that the duplication and divergence of ets proto-oncogenes responsible for generating the multigene family occurred concomitantly with the development of metazoan animals. In addition, these data corroborate other recent molecular evidence in providing strong support for the monophyletic origin of all multicellular animals, including sponges. PMID- 8346027 TI - Synthesis and properties of oligodeoxynucleotides containing the analogue 2' deoxy-4'-thiothymidine. AB - The 2'-deoxythymidine analogue 2'-deoxy-4'-thiothymidine has been incorporated, using standard methodology, into a series of dodecadeoxynucleotides containing the EcoRV restriction endonuclease recognition site (GATATC). The stability of these oligodeoxynucleotides and their ability to act as substrates for the restriction endonuclease and associated methylase have been compared with a normal unmodified oligodeoxynucleotide. No problems were encountered in the synthesis despite the presence of a potentially oxidisable sulfur atom in the sugar ring. The analogue had very little effect on the melting temperature of the self-complementary oligoeoxynucleotides so synthesised and all had a CD spectrum compatible with a B-DNA structure. The oligodeoxynucleotide containing one analogue in each strand within the recognition site, adjacent to the bond to be cleaved (i.e. GAXATC, where X is 2'-deoxy-4'-thiothymidine), was neither a substrate for the endonuclease nor was recognized by the associated methylase. When still within the recognition hexanucleotide but two further residues removed from the site of cleavage (i.e. GATAXC), the oligodeoxynucleotide was a poor substrate for both the endonuclease and methylase. Binding of the oligodeoxynucleotide to the endonuclease was unaffected but the kcat value was only 0.03% of the value obtained for the parent oligodeoxynucleotide. These results show that the incorporation of 2'-deoxy-4'-thionucleosides into synthetic oligodeoxynucleotides may shed light on subtle interactions between proteins and their normal substrates and may also show why 2'-deoxy-4'-thiothymidine itself is so toxic in cell culture. PMID- 8346028 TI - The application of the AMB protective group in the solid-phase synthesis of methylphosphonate DNA analogues. AB - Partially methylphosphonate-modified oligodeoxynucleotides were synthesized on solid-phase by employing the easily removable 2-(acetoxymethyl)benzoyl (AMB) group as base-protecting group. Although a rapid AMB deprotection can be accomplished in methanolic potassium carbonate, the lability of the methylphosphonate linkage towards potassium carbonate/methanol excludes the use of this deprotection reagent. Thus, saturated ammonia solution in methanol was investigated as an alternative reagent for AMB removal. It is demonstrated that the combination of the AMB protective group and ammonia/methanol as deprotection reagent significantly improves the synthesis of methylphosphonate-modified DNA fragments. A mild overnight treatment at room temperature is sufficient for complete removal of the AMB group, whereas deprotection of conventionally protected oligonucleotides requires much longer exposure to basic conditions at elevated temperatures. PMID- 8346029 TI - Human snRNP polypeptide D1 promotes pre-mRNA splicing in yeast and defines nonessential yeast Smd1p sequences. AB - Parallel investigations of yeast and metazoan pre-mRNA splicing have documented enormous complexity in the nucleic acid and protein components of the cellular splicing apparatus, the spliceosome. The degree to which yeast and metazoan spliceosomal proteins differ in composition and structure is currently unknown. In this report we demonstrate that the human small nuclear ribonucleoprotein (snRNP) polypeptide D1 complements the cell lethality, splicing deficiency, and snRNA instability phenotypes associated with a yeast smd1 null allele. Mutational analysis of yeast SMD1, guided by a comparison of the predicted yeast and human proteins, reveals that a large, nonconserved portion of Smd1p is dispensable for biological activity. These observations firmly establish D1 as an essential component of the cellular splicing apparatus and suggest that yeast and metazoa are remarkably similar in the polypeptides guiding early snRNP assembly. PMID- 8346030 TI - Characterization of a DNA binding domain in the C-terminus of HIV-1 integrase by deletion mutagenesis. AB - The integrase (IN) protein of human immunodeficiency virus type 1 (HIV-1) catalyzes site-specific cleavage of 2 bases from the viral long terminal repeat (LTR) sequence yet it binds DNA with little DNA sequence specificity. We have previously demonstrated that the C-terminal half of IN (amino acids 154-288) possesses a DNA binding domain. In order to further characterize this region, a series of clones expressing truncated forms of IN as N-terminal fusion proteins in E.coli were constructed and analyzed by Southwestern blotting. Proteins containing amino acids 1-263, 1-248 and 170-288 retained the ability to bind DNA, whereas a protein containing amino acids 1-180 showed no detectable DNA binding. This defines a DNA binding domain contained within amino acids 180-248. This region contains an arrangement of 9 lysine and arginine residues each separated by 2-4 amino acids (KxxxKxxxKxxxxRxxxRxxRxxxxKxxxKxxxK), spanning amino acids 211 244, which is conserved in all HIV-1 isolates. A clone expressing full-length IN with a C-terminal fusion of 16 amino acids was able to bind DNA comparably to a cloned protein with a free C-terminus, and an IN-specific monoclonal antibody which recognizes an epitope contained within amino acids 264-279 was unable to block DNA binding, supporting the evidence that a region necessary for binding lies upstream of amino acid 264. PMID- 8346031 TI - Complete sequence of Euglena gracilis chloroplast DNA. AB - We report the complete DNA sequence of the Euglena gracilis, Pringsheim strain Z chloroplast genome. This circular DNA is 143,170 bp, counting only one copy of a 54 bp tandem repeat sequence that is present in variable copy number within a single culture. The overall organization of the genome involves a tandem array of three complete and one partial ribosomal RNA operons, and a large single copy region. There are genes for the 16S, 5S, and 23S rRNAs of the 70S chloroplast ribosomes, 27 different tRNA species, 21 ribosomal proteins plus the gene for elongation factor EF-Tu, three RNA polymerase subunits, and 27 known photosynthesis-related polypeptides. Several putative genes of unknown function have also been identified, including five within large introns, and five with amino acid sequence similarity to genes in other organisms. This genome contains at least 149 introns. There are 72 individual group II introns, 46 individual group III introns, 10 group II introns and 18 group III introns that are components of twintrons (introns-within-introns), and three additional introns suspected to be twintrons composed of multiple group II and/or group III introns, but not yet characterized. At least 54,804 bp, or 38.3% of the total DNA content is represented by introns. PMID- 8346032 TI - Regulation of tissue-specific expression of the esterase S gene in Drosophila virilis. AB - The esterase S gene (estS) of Drosophila virilis is specifically expressed in the ejaculatory bulbs of males. Its sequencing shows similarities between estS product and other esterases of different origin. The transcription of estS in ejaculatory bulbs is at least 2 orders of magnitude higher than in other tissues of males. Two promoters, P1 (distal) and P2 (proximal), and two different transcripts were identified. The promoter P2 is used much more efficiently, and in a stringent, tissue-specific manner. The transcription from P1 takes place in different tissues and stages of development of D. virilis. However, the mRNA transcribed from P1 seems to be inactive in translation as there are three open reading frames (ORF) between P1 and P2, which may block the translation in P1 initiated mRNA. Insertion of sequence containing the three ORFs into the 5' untranslated region of the CAT gene strongly inhibited expression of CAT. Point mutations destroying the three ORFs completely eliminate the inhibitory effect. Hence tissue-specific expression of the estS gene may depend on control at the level of transcription, promoter selection and translation. PMID- 8346033 TI - Electroporation enhances c-myc antisense oligodeoxynucleotide efficacy. AB - Obtaining high transfection efficiencies and achieving appropriate intracellular concentrations and localization are two of the most important barriers to the implementation of gene targeted therapy. The efficiency of endogenous uptake of oligodeoxynucleotides (ODNs) varies from cell type to cell type and may be a limiting factor of antisense efficacy. The use of electroporation to obtain high intracellular concentrations of a synthetic ODN in essentially 100% of viable cells is described. It is also shown that the transfected ODNs initially localize to the nucleus and remain there for at least 48 hours. The cellular trafficking of electroporated ODNs is shown to be an energy dependent process. Targeting of the c-myc proto-oncogene of U937 cells by electroporation of phosphorothioate modified ODNs results in rapid and specific suppression of this gene at ODN concentrations much lower than would otherwise be required. This technique appears to be applicable to a variety of cell types and may represent a powerful new investigate tool as well as a promising approach to the ex vivo treatment of hematologic disorders. PMID- 8346034 TI - Pw Sox-1: the first member of the Sox gene family in Urodeles. PMID- 8346035 TI - Identification of a Candida utilis gene encoding ribosomal protein L7: evidence for two divergent subclasses of the eukaryotic ribosomal protein L7 family. PMID- 8346036 TI - Cloning and sequencing of the gene encoding the ribosomal L7/L12-like protein of Mycobacterium bovis BCG. PMID- 8346037 TI - Coding sequence of ERF-1, the human homologue of Tis11b/cMG1, members of the Tis11 family of early response genes. PMID- 8346038 TI - Nucleotide sequence of the mini-plasmid pSLG33 from Streptomyces lavendulae grasserius RIA746. PMID- 8346039 TI - The 18S ribosomal RNA gene of a crustacean branchiopod Bosmina longirostris: comparison with another branchiopod Artemia salina. PMID- 8346040 TI - Cloning of a human GHF-1/Pit-1 cDNA variant. PMID- 8346041 TI - BseRI a novel restriction endonuclease from a Bacillus species which recognizes the sequence 5'...GAGGAG...3'. PMID- 8346042 TI - Cloning and analysis of the macronuclear gene for histone H1 from Euplotes eurystomus. PMID- 8346043 TI - Nucleotide sequences and secondary structures of four tRNA genes in mitochondrial DNA of Hansenula wingei yeast. PMID- 8346044 TI - Chemical Cleveland mapping: a rapid technique for characterization of crosslinked nucleic acid-protein complexes. PMID- 8346045 TI - Polymerase-chain reaction: analysis of DNA/DNA hybridization by capillary electrophoresis. PMID- 8346046 TI - Determination of messenger RNA 5'-ends by reverse transcription of the cap structure. PMID- 8346047 TI - Rapid cloning by homologous recombination in vivo. PMID- 8346048 TI - DISEC-TRISEC: di- and trinucleotide-sticky-end cloning of PCR-amplified DNA. PMID- 8346049 TI - Collaborative interdisciplinary bioethical decision making in intensive care units. AB - There is strong support in the literature for involvement of nurses with patients and physicians in bioethical decision making about patient care. There are indications that nurses and physicians have different beliefs about decisions made and about the decision-making processes, such as who should be involved and what factors should influence such decisions. The literature also demonstrates that nurses often disagree with physicians or are not involved in ethical decision making or both. Interdisciplinary collaboration has been proposed to improve decision making and recommended for health care giving generally. There is research support for the benefit of collaboration in care giving. Ethical principles also support collaborative decision making, involving nurses, as well as physicians, patients, and family. With collaboration there is sharing of information and perspectives, respect for patient and family autonomy, and disclosure. More studies of interdisciplinary bioethical decision making are needed, measuring both professions' perceptions of their roles in ethical decision making, as well as examining the effects of collaboration on care outcomes. PMID- 8346050 TI - The 'doctor-nurse game': a comparison of 100 years--1888-1990. PMID- 8346051 TI - The passionate connection: feminism invigorates the teaching of nursing. PMID- 8346052 TI - 'Unknowing': toward another pattern of knowing in nursing. AB - Knowing is wonderful, but it is just a guiding means. Unknowing is a condition of openness. This unknowing in the intersubjective space of two people or people of two cultures allows others to be. This art of unknowing may enable a nurse to understand, with empathy, the actual essence of the meaning an experience has for a patient. This pattern of unknowing focused herein on the intersubjective whole between patient and nurse is applicable as well to learning in a more formal sense. To be open to learning one needs to posture oneself in a position of unknowing to hear a colleague, a teacher, a student. To provide and find openness is to be able to say, "I never thought about it that way," and at once experience the wonderment of coming upon an "unknown." PMID- 8346053 TI - Problems and progress as Australia adopts the bachelor's degree as the only entry to nursing practice. PMID- 8346054 TI - Castles in the air. Interview by Andrew Cole. PMID- 8346055 TI - Alternative approach. Interview by Tricia Reid. PMID- 8346056 TI - Off target. PMID- 8346057 TI - School for scandal? PMID- 8346058 TI - Generic nurse. A dream ticket? PMID- 8346060 TI - Targets go up in smoke. PMID- 8346059 TI - Generic nurse. Breaking the mould. PMID- 8346061 TI - Generic nurse. A dilution of skills. PMID- 8346062 TI - Health promotion. Education on the rocks. PMID- 8346063 TI - Transplants. Given the choice. PMID- 8346064 TI - Professional development. A guiding light. PMID- 8346065 TI - Bedside manners. PMID- 8346066 TI - Stress. Taking control. PMID- 8346067 TI - Helpline will urge HIV nurses to keep quiet. PMID- 8346068 TI - Here comes the sun. PMID- 8346069 TI - Starting from scratch. PMID- 8346070 TI - Creche course in hygiene. PMID- 8346071 TI - Help from EPI info. PMID- 8346072 TI - RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells. AB - The RRR-alpha-tocopheryl succinate form of vitamin E inhibits the proliferation of estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines in a dose-dependent manner in vitro. Analyses of cell-conditioned medium from RRR-alpha-tocopheryl succinate growth-inhibited cells revealed the presence of a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of the TGF-beta-responsive Mv1Lu-CCL-64 mink lung and murine CTLL-2 cell lines, 2) combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, and 3) neutralization of the antiproliferative activity in the conditioned media by antibodies specific for TGF-beta. PMID- 8346073 TI - RRR-alpha-tocopheryl succinate inhibition of lectin-induced T cell proliferation. AB - The effect of RRR-alpha-tocopheryl succinate (VES) on lectin-induced chicken T cell proliferation was investigated. The T cell mitogens concanavalin A and phytohemagglutinin induce chicken thymic and splenic T cell proliferation. Addition of VES to the in vitro cultures inhibited T cell proliferation in a dose dependent manner. Addition of VES to spleen cell cultures at different times after mitogen stimulation also suppressed T cell mitogenesis, suggesting that VES is not mediating its antiproliferative effects by interfering with ligand (mitogen)-receptor binding or early ligand-bound receptor-signaling events. Three lines of evidence suggest that the growth-inhibitory properties of VES are unique and may not involve antioxidant properties. 1) Three other forms of vitamin E, dl alpha-tocopherol, d-alpha-tocopherol, and d-alpha-tocopherol acetate, do not inhibit the proliferation of mitogen-stimulated chicken spleen cells. 2) Spleen cells were treated with an inhibitor of nonspecific esterases to prevent the conversion of VES, which does not exhibit antioxidant properties to d-alpha tocopherol, a lipid-soluble antioxidant. Treatment of spleen cells with the inhibitor did not affect VES's growth-inhibitory properties. 3) Trolox, a water soluble vitamin E analogue with potent antioxidant properties and two lipid soluble antioxidants, butylated hydroxyanisole and butylated hydroxytoluene, did not inhibit mitogen-induced T cell proliferation. Attempts to reverse VES's antiproliferative effects by addition of exogenous interleukin-2 or addition of sodium selenite, an enhancer of interleukin-2 receptors, failed. Acetylsalicylic acid had no effect on VES's inhibition of mitogen-activated T cell proliferation. These studies support the role of VES as a growth inhibitor of lectin-activated normal T cells in chickens. PMID- 8346074 TI - Lack of significant changes in nutrition-related parameters with tumor necrosis factor treatment of cancer. AB - Cancer and its therapies frequently produce anorexia and cachexia. In this study, the acute (3 days) and chronic (4 wks) nutrition-related effects of cancer therapy with recombinant human tumor necrosis factor (rHuTNF) were investigated and described. Nutritional status, as measured by body weight and body composition (body fat and lean-to-fat ratio) with use of bioelectrical impedance, did not appear to deteriorate. None of the serum lipids changed significantly, but triglycerides did rise modestly over four weeks of therapy. Glucose and the peptide hormones (insulin, C-peptide, glucagon, and pancreatic polypeptide) thought to affect appetite did not change with rHuTNF therapy. Therefore, although TNF is thought to contribute to wasting in animal models, it had no negative effect on nutritional status in our small sample. The lack of adverse effect noted in this study is possibly due to the low dose level of rHuTNF or to adaptation. PMID- 8346075 TI - Mitotic activity in colorectal mucosa of healthy subjects in two Italian areas with different dietary habits. AB - The proliferative activity was evaluated in colorectal biopsies of 39 healthy subjects living in two distinct geographical areas, Trieste in northern and Florence in central Italy. Subjects living in Trieste had a significantly higher mitotic activity compared with subjects living in Florence (mitoses/cells counted x 100 were 0.17 +/- 0.04 in Trieste and 0.089 +/- 0.02 in Florence). The results of a dietary questionnaire also showed that subjects in Trieste consumed significantly fewer starches, fibers, nitrites, and proteins. However, no correlation was evident between the consumption of these nutrients and intestinal proliferation. PMID- 8346076 TI - Studies of immunomodulating actions of carotenoids. II. Astaxanthin enhances in vitro antibody production to T-dependent antigens without facilitating polyclonal B-cell activation. AB - Previously we have shown that astaxanthin, a carotenoid without provitamin A activity, enhances in vitro antibody (Ab) production to sheep red blood cells in normal B6 mice. In this study, we further attempted to examine the mechanisms of this enhancing action of carotenoids on specific Ab production in vitro in relation to different antigen (Ag) stimuli, cytokine production, and T- and B cell interactions in both normal and autoimmune strains of mice. When the actions of carotenoids were tested in normal strains of mice, we found that astaxanthin enhanced in vitro Ab production to T cell-dependent Ag, but not to T-independent Ag, and did not augment total immunoglobulin production. Astaxanthin exerted maximum enhancing actions when it was present at the initial period of Ag priming. This action of astaxanthin was abolished when T cells were depleted from spleen cell suspensions and appeared to require direct interactions between T and B cells. The results also indicated that carotenoids may modulate the production of interferon-tau in this assay system. When the actions of carotenoids were tested in autoimmune-prone MRL and NZB mice, the enhancing action of astaxanthin on in vitro Ab production was less significant. Furthermore, carotenoids did not potentiate or augment spontaneous Ab and immunoglobulin production by spleen cells in these strains. Taken together, carotenoids without provitamin A activity may be able to augment in vitro specific Ab production to T cell-dependent Ag partly through affecting the initial stage of Ag presentation without facilitating polyclonal B-cell activation or autoantibody production. PMID- 8346077 TI - Preparation and production of a cancer chemopreventive agent, Bowman-Birk inhibitor concentrate. AB - We describe our studies to produce an extract of soybeans with anticarcinogenic activity that we believe will be useful as a human cancer chemopreventive agent for several different organs. The anticarcinogenic activity of the extract is thought to be due to chymotrypsin inhibitor activity, which is due to the Bowman Birk protease inhibitor (BBI) present in the extract, termed BBI concentrate (BBIC). We describe the contents of BBIC, the ability of BBIC to inhibit malignant transformation in vitro in terms of its chymotrypsin inhibitor activity, and the results of long-term toxicity studies in which mice and rats were exposed to high levels of BBIC for long periods of time. PMID- 8346078 TI - Moderate beer consumption and the risk of colorectal cancer. AB - The relationship between beer consumption and the risk of colon and rectal cancer was considered in a case-control study conducted in northern Italy. The study was based on 828 histologically confirmed incident cases of colon cancer, 498 of rectal cancer, and 2,024 controls in hospital for a wide spectrum of acute, nonneoplastic, nonalcohol-related diseases. Beer drinking was reported by 6% of colon cancer cases, 7% of rectal cancer cases, and 10% of controls; regular beer drinkers (> or = 1 drinks/day) made up 2.6% of colon cancer cases, 3.2% of rectal cancer cases, and 4.1% of controls. Thus the multivariate relative risks (RR) for irregular drinkers were 0.6 [95% confidence interval (CI) 0.4-1.0] for colon and 0.7 (95% CI 0.4-1.2) for rectum. Corresponding values for regular drinkers were 0.7 (95% CI 0.4-1.2) for colon and 0.9 (95% CI 0.5-1.5) for rectal cancer. Despite the low frequency of beer drinking in this study, and hence its limited statistical power, the originality of the population in terms of colorectal cancer incidence, patterns of risk factor exposure, and the large dataset provide interesting and useful confirmation that moderate beer drinking is not associated with elevated colon or rectal cancer risk. PMID- 8346080 TI - Caraway oil inhibits skin tumors in female BALB/c mice. AB - Caraway oil, supplemented in diet or painted on the skin, inhibited 7,12 dimethylbenz[a]anthracene- (DMBA) and croton oil-induced skin tumors in female BALB/c mice. The inhibition was manifested by disappearance of carcinomas, reduced incidence and number of papillomas, delay of their appearance, retardation of their development, and regression of already established papillomas. Caraway oil is more effective when topically applied than when supplemented in the diet. PMID- 8346079 TI - Dietary fatty acid modulation of events associated with mouse skin tumor promotion. AB - Increasing levels of dietary corn oil have been correlated with inhibition of 12 O-tetradecanoylphorbol-13-acetate-(TPA) promoted skin tumorigenesis in mice (Leyton et al. Cancer Res. 51, 907-915, 1991). This study was undertaken to assess the effects of dietary corn oil on several events associated with tumor promotion. Three semipurified diets containing 15% (wt/wt) total fat with increasing levels of linoleate (0.8%, 4.5%, and 8.4%) supplied by corn oil were fed to mice for at least four weeks. Although incorporation of linoleate into epidermal phosphatidylcholine increased with increasing amounts of dietary corn oil, the elongated desaturated product of linoleate, arachidonate, was similar or decreased slightly in mice fed the three diets. Minimal activity of delta 6 desaturase, the rate-limiting enzyme in the conversion of linoleate to arachidonic acid, was found in the epidermis compared with the liver, suggesting that linoleate is not converted to arachidonic acid in the skin. Subcellular distribution of protein kinase C was altered in mice fed 0.8% linoleate, where 69% of protein kinase C activity was in the cytosol compared with 78% and 74% for groups fed 4.5% and 8.4% linoleate, respectively. Activation of partially purified protein kinase C isolated from mouse epidermis by linoleate was significantly lower (p < 0.01) than that isolated by arachidonic acid. TPA induced vascular permeability was significantly greater (p < 0.05), whereas hyperplasia 48 hours after TPA treatment was significantly lower, in mice fed the 8.4% linoleate diet. However, TPA induction of ornithine decarboxylase activity did not appear to be significantly modified by dietary linoleate. These data suggest that cellular processes associated with carcinogenesis are affected by the level of dietary linoleate. PMID- 8346081 TI - Dietary factors and breast cancer risk in Vaud, Switzerland. AB - The relationship between dietary factors and the risk of breast cancer was investigated in a case-control study conducted in the Canton of Vaud, Switzerland as a pilot phase for a larger cooperative study within the SEARCH Programme of the International Agency for Research on Cancer (Lyon, France). A total of 107 incident, histologically confirmed cases of breast cancer and 318 controls admitted to hospital for acute, nonhormone-related, gynecological, metabolic, or neoplastic disorders were interviewed. Significant direct trends in risk were observed with total energy intake [relative risk (RR) for highest vs. lowest intake tertile = 1.9] and, after allowance for energy intake, with frequency of consumption of various types of meat (RR = 2.1 for the highest tertile), cheese (RR = 2.7), and alcohol (RR = 2.1). Significant protections, on the order of 40 60% reductions for the highest vs. lowest consumption tertile, were conferred by total green vegetable consumption, selected types of vegetables and fruits (cucumbers, onions, pears), and a summary index of beta-carotene intake (RR = 0.4 for highest consumption tertile). Thus the present study confirmed the existence of an unfavorable dietary pattern for breast cancer risk (characterized by high calorie, selected sources of animal fat and alcohol intake). Moreover, a significant protection could be gained by consuming a diet rich in vegetables and perhaps fruits. PMID- 8346082 TI - Theophylline toxicity in children: a retrospective review. AB - Theophylline has been a mainstay of asthma therapy despite its narrow therapeutic index, which makes toxicity a common problem. To study toxicity in children, we reviewed hospital laboratory records (1980 to 1988) and identified cases (n = 163) with theophylline concentrations of > 133 mumol/L (24 micrograms/ml). We reviewed these cases for symptoms of theophylline intoxication; we were interested in associating symptoms with serum drug concentrations and in understanding how intoxication occurred. The median patient age was 3.0 years; 40/163 were younger than one year. Males were 90/163 patients (55%). Patients were classified by pattern of ingestion: 20 patients had acute ingestions; 17 patients had an acute ingestion while on chronic medication; and 126 patients became toxic on chronic therapy. Symptoms were absent in 44/150 patients (29%) with theophylline concentrations of 139 to 278 mumol/L (25-50 micrograms/ml); concentrations of > 278 mumol/L (50 micrograms/ml) were always associated with symptoms. The most common clinical symptoms were tachycardia (47%) and vomiting (52%); both occurred more frequently with higher theophylline concentrations (P < 0.002 and P < 0.01). Nine patients had seizures, including five who were previously neurologically normal. Seizures developed with a theophylline concentration of < 278 mumol/L (50 micrograms/ml) in four of these five patients. There was no association between seizures and patient age or between seizures and a particular pattern of theophylline use. In 105/126 cases of intoxication associated with chronic use, the cause of the intoxication could not be determined. Appropriate management of theophylline toxicity can occur only if toxicity is recognized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346083 TI - General trauma in a pediatric emergency department: spectrum and consultation patterns. AB - To assess the consultation patterns of pediatric emergency physicians in the management of injured children and to describe the spectrum of pediatric trauma, we retrospectively reviewed 601 patients treated in the emergency department for injuries during four one-week periods at a designated level I regional pediatric trauma center (50,000 patients/year) with a pediatric emergency medicine fellowship. The majority (94%) of pediatric trauma was minor; only 2% of children had injuries severe enough to require direct transfer to the operating room. The highest volume of patients, the greatest number of consultations, and the majority of admissions to the operating room occurred between 4 PM and midnight. No patients went to the operating room on the night shift. Musculoskeletal injuries constituted the predominant category of pediatric trauma, and lacerations were the most common specific injury. One half of all procedures involved laceration repair, and one third involved splinting or casting. Four hundred ten patients (68%) were managed by physicians in the emergency department without consultation. The orthopedic service performed one half of all consultations and admitted the largest number of patients; the majority of patients taken directly to the operating room had musculoskeletal injuries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346084 TI - Clinical presentation and radiographic identification of small bowel rupture following blunt trauma in children. AB - The incidence of significant intraabdominal injuries from blunt trauma in children is low (1-8%); however, a missed intestinal laceration may result in a devastating, if not morbid, consequence. We present retrospective case studies of eight children with intestinal lacerations following blunt trauma. Each patient has a unique anatomic defect with misleading initial laboratory and radiographic studies. We did not find a single laboratory or roentgenographic study to be consistently reliable for diagnosis of hollow viscus laceration. The combination of a high index of suspicion and serial abdominal examinations, coupled with subsequent comparative laboratory and radiographic evaluations, proved most reliable in identifying patients with intestinal injury. PMID- 8346085 TI - Pediatric education in emergency medicine residency programs--10 years later. AB - The purpose of this study is to examine the changes in the pediatric emergency medicine education of emergency medicine (EM) residents over the last decade. Questionnaires were mailed to the training directors of all EM residency programs. Sixty-five programs (79%) responded. While children represent 29 +/- 2% of all patients seen in the institutions surveyed, only 17 programs (26%) provide more than six months of pediatric education, ie, no increase in the last decade. EM residents frequently rotate through pediatric emergency departments (72%), inpatient pediatric wards (51%), and pediatric intensive care units (88%). Most physicians in charge of pediatric emergency medicine education are emergency medicine trained (75% vs 29% in 1981), and only 12% are pediatric emergency medicine fellowship trained. Despite several improvements and the increased satisfaction of program directors, the pediatric component of EM residents' training continues to be disproportionate to the number of children in the emergency medicine patient population. Specialists in pediatric emergency medicine should strive to play a more significant role in the pediatric education of EM residents. PMID- 8346086 TI - Two-week-old infant with isopropanol intoxication. AB - Isopropyl alcohol continues to be a frequent toxicologic exposure. However, no cases involving the newborn period have been described. A 14-day-old male infant presented to the emergency department (ED) with the mother's chief complaint that "He is not himself." Physical examination observed the infant to be lethargic and hypotonic. Laboratory evaluation revealed a positive urine drug screen for isopropanol and acetone. Elevated serum levels (in mg/dl) of isopropanol/acetone at 2:45, 4:15, 11:10, and 29:53 hours postpresentation were 101/136, 81/149, 20/155, and 5/72, respectively. Overall, this patient did remarkably well with minimal supportive care and was noted to have a normal neurologic examination within 10 hours of presentation despite rising serum acetone levels. This case brings into question the hypothesis that acetone, a metabolite of isopropanol, prolongs central nervous system depression in acute isopropyl alcohol intoxication. The importance of urine drug screens in children who present to the ED with unusual neurologic examinations is appreciated. PMID- 8346087 TI - Fungal osteomyelitis and sepsis from intraosseous infusion. PMID- 8346088 TI - Haemophilus influenzae meningitis in twins. PMID- 8346089 TI - Aerosolized atropine as an unusual cause of anisocoria in a child with asthma. PMID- 8346090 TI - Childhood sledding injuries in 1990-91. AB - Sledding injuries are a common wintertime problem. To better characterize these injuries, three analyses were done: a retrospective chart review of all injured sledders at St. Louis Children's Hospital (SLCH) in the winter of 1990-91, a review of Consumer Product Safety Commission (CPSC) injury data for 1990, and measurements of sledding speeds. Analyses of the SLCH data and the CPSC data yielded similar results. Younger children incur more head injuries, while older children incur more extremity injuries. The SLCH data indicate that most injuries occur close to home when a sledder strikes a fixed object in his path. Velocities of 10 to 20 mph may be easily achieved. Injury prevention includes appropriate selection of sledding site, use of protective clothing, and refraining from sledding at times of highest risk. PMID- 8346092 TI - Blood warmers: dry heat, water bath, circulating fluid. PMID- 8346091 TI - Childhood injury: a current perspective. AB - The majority of childhood injuries requiring admission are due to traffic-related injury, falls, and burns. Many of these injuries are preventable. In the case of the unpreventable, unintentional injury, the natural history of the injury and outcome can be altered by adherence to established safety standards. New standards also need to be set. There is definitely room for improvement in vehicular restraint systems for the smaller and younger passengers. It is known that wearing bicycle helmets, using safety belts, securing firearms in the home, and controlling hot water heater temperature levels will prevent or lessen injury in children. This information is being promulgated to communities by activities such as the National SAFE KIDS Campaign, a program of Children's National Medical Center sponsored by Johnson & Johnson Family of Companies and the National Safety Council. This campaign emphasizes important aspects of childhood injury: scope, causes, and prevention. Questions about the most devastating of childhood injuries, child abuse and assault related to violent crime, are more complex and the answers elusive. The study of patterns of injury in children highlights the need to implement new strategies aimed at prevention. At the same time, valuable information is obtained about specific injuries and responses seen in children that set them apart from adults. PMID- 8346093 TI - Jerky movements in a child. PMID- 8346094 TI - A 19-year-old thalassemic with an irregular pulse. PMID- 8346095 TI - Controversies in Pediatric Emergency Medicine. To do or not to do. PMID- 8346096 TI - Case 02-1993: a three-year-old boy with acute-onset abdominal pain. PMID- 8346097 TI - The utility of skull radiographs in the evaluation of asymptomatic infants following minor head injury. PMID- 8346098 TI - Urticaria in children. AB - The etiologic factors responsible for urticaria were analyzed in 44 children seen in the Urticaria Clinic, a referral center of the Dermatology Department. Of these, 23 were girls and 21 boys. Nine (20.5%) had acute urticaria and 25 (79.5%) were diagnosed as having chronic urticaria. A definitive etiology factor was identified in 18 (40%) patients. Of these, 15 had physical urticarias; in 2 foods and in 1 drug was incriminated. Probable etiologic factors were identified in 19 (43%) patients, in 5 (11.3%) of whom more than one factor was identified. In 11 (25%) children, it was not possible to establish the cause. Our study suggests that etiologic factors of urticaria are more readily identifiable in children than in adults. PMID- 8346099 TI - Trichothiodystrophy: ultrastructural studies of two patients. AB - An 18-month-old and an 8-year-old girl had trichothiodystrophy (TTD). Microscopic observation of the hair under polarized light showed typical alternation of bright and dark bands; amino acid analysis of the hair demonstrated a marked reduction of cystine levels. Both patients had skin lesions consisting in the older child of diffuse follicular keratosis since birth, and in the younger of an ichthyosiform dermatitis on the lower legs that appeared at age 4 months. Ultrastructural studies of the skin showed striking similarities in both cases: perinuclear vacuoles with a unit membrane in the keratinocytes, and dispersed, irregularly arranged bundles of tonofilaments particularly at the desmosome junction. The origin of the vacuoles is unknown; the abnormalities of the tonofilaments could be explained on the basis of a generalized abnormality in sulfur-containing proteins, reflecting a disturbance in the synthesis of keratins. These electron microscopy findings could be considered as a peculiar feature of ichthyotic skin in patients with TTD. PMID- 8346101 TI - Benign pigmented apocrine vulvar hamartomas. AB - Pigmented vulvar lesions were observed in a child during a sexual abuse evaluation. Gross examination of the lesions appeared most consistent with bowenoid papulosis; however, biopsy confirmed the lesions to be pigmented apocrine hamartomas. To our knowledge, these rare and benign tumors have never been described as pigmented, but should be added to the differential diagnosis of pigmented vulvar lesions. PMID- 8346100 TI - Trichothiodystrophy and associated anomalies: a variant of SIBIDS or new symptom complex? AB - Trichothiodystrophy is characterized by sparse, short, sulfur-deficient hair. Numerous symptom complexes have been described in which the hair abnormality represents a constant feature. We report a boy with trichothiodystrophy, ichthyotic skin changes, onychodystrophy, chronic neutropenia, osteosclerosis, hypothyroidism, nystagmus, growth and mental retardation, and microcephaly, who developed a progressive encephalopathy with ataxia and optic atrophy at 2.5 years of age. In addition to a deficient cystine level identified on a hair sample, a disturbance in the composition of other amino acids was present. Although features were reminiscent of osteosclerosis, ichthyosis, brittle hair due to trichothiodystrophy, impaired intelligence, decreased fertility, and short stature (SIBIDS) and could represent a variant of this disorder, findings in our patient may reflect a new trichothiodystrophy symptom complex that carries a poor prognosis for survival beyond childhood. PMID- 8346102 TI - Erythema elevatum diutinum associated with celiac disease: response to a gluten free diet. AB - An 11-year-old girl with a history of insulin-dependent diabetes mellitus had erythema elevatum diutinum (EED) associated with a celiac disease related to a possible kidney disease. Dapsone did not improve the skin manifestations. However, the lesions disappeared after a gluten-free diet was begun. To our knowledge, this report describes the first case of EED in a patient with celiac disease. PMID- 8346103 TI - Penile purpura as a manifestation of lichen sclerosus et atrophicus. AB - Heightened public and professional awareness of the sexual abuse of children demands that physicians be able to distinguish lesions associated with sexual abuse from those caused by primary skin disorders. Purpura is an occasional manifestation of pediatric lichen sclerosus et atrophicus (LSA), especially when the vulva is affected. We report a 12-year-old boy with penile purpura that occasioned a consideration of sexual abuse but proved to be due to LSA. PMID- 8346104 TI - Lichen planus in children: a case report. AB - Lichen planus (LP) is rare in children. A review of the literature reveals that it has some peculiarities with respect to sex, localization, clinical aspect, race, and family history. We present an Indian child with the documented peculiarities of infantile LP. A comparison of LP and graft-versus-host disease points to the importance of thymic involution in the pathogenesis of the former, which could explain the rarity of this disorder in infants. PMID- 8346105 TI - Scabies of the scalp mimicking seborrheic dermatitis in immunocompromised patients. AB - Two children with acute lymphoblastic leukemia undergoing chemotherapy had a special form of scabies characterized by fine scaling of the scalp simulating seborrheic dermatitis. Pruritus was mild or absent. Immunocompromised children and adults should receive whole-body and scalp antiscabietic treatment. PMID- 8346106 TI - Papular xanthoma in children: report and immunohistochemical study. AB - Papular xanthoma was diagnosed in a 14-month-old boy. The eruption cleared spontaneously within four years. Immunohistopathologic study revealed that the predominant foamy histiocytic cells had the phenotypic features of the dermal dendrocyte. Giant multinucleated cells, which showed characteristics of monocyte derived macrophages, were also present. We suggest classifying diseases derived from dermal dendrocytes into a separate group of histiocytoses. PMID- 8346107 TI - Congenital smooth muscle hamartoma of the skin. AB - A 2-month-old white girl had a congenital, tan-colored, slightly elevated, 3 x 2 cm plaque on the left midback. Clinically, the lesion was suspected to be a solitary mastocytoma. Rubbing the lesion produced a transient erythema and edema that was similar to Darier sign seen in mastocytoma. Analysis of a skin biopsy specimen revealed a smooth muscle hamartoma; special stains did not show evidence of increased numbers of mast cells. This relatively uncommon condition can be confused with a variety of other cutaneous diseases. Light microscopic examination of a skin biopsy specimen establishes the diagnosis. A review of the approximately 50 cases reported in the literature showed that there is no known associated systemic involvement or malignant transformation. The clinical lesions usually become less prominent with time. PMID- 8346108 TI - Case report of Darier disease localized to the vulva in a 5-year-old girl. AB - A 5-year-old girl with Darier disease had numerous verrucous papules coalescing into plaques on both labia majora of approximately one year's duration. She was diagnosed as having genital warts, raising the suspicion of sexual abuse. Subsequently, a biopsy specimen from one of the vulvar lesions revealed histologic characteristics consistent with a diagnosis of Darier disease. The case is unusual for the age of onset and the site of initial involvement, and stresses the importance of including acantholytic disorders such as Darier disease in the differential diagnosis of a child with clinically verrucous lesions. PMID- 8346109 TI - Occult spinal dysraphism: a neurosurgical problem with a dermatologic hallmark. AB - Lumbosacral congenital cutaneous lesions have been recognized for a long time by neurologists and neurosurgeons as markers of occult spinal defects, but only a few cases have been published and discussed in the dermatologic literature. Based on a case report, we emphasize the importance of early diagnosis of these lesions, the use of new diagnostic techniques, and the correct management. PMID- 8346110 TI - Granular cell tumor of the vulva. AB - Granular cell tumors are uncommon in the vulva. We cared for a child who had a solitary vulvar tumor since infancy. PMID- 8346111 TI - Linear and whorled nevoid hypermelanosis. AB - A case of hyperpigmentation distributed in streaks and whorls was recently delineated and separated from a confusing number of pigmentary disorders. A 13 year-old boy had hyperpigmented, reticulate spots on his trunk and neck in a linear and whorled distribution following the lines of Blaschko. Onset was at age 1 year. Histologically, the spots showed increased melanin in the basal layer of the epidermis, but no increase in melanocytes, incontinence of pigment, or melanophages were seen in the dermis. The karyotype was 46,XY and there was no evidence of chromosomal mosaicism or chimerism. This entity represents a disorder separated recently from other pigmentary alterations that follow Blaschko lines, such as Bloch-Sulzberger incontinentia pigmenti, hypomelanosis of Ito, early systematized epidermal nevus, and chimerism. PMID- 8346113 TI - Encephalocraniocutaneous lipomatosis: case report and review of the literature. AB - Encephalocraniocutaneous lipomatosis is a congenital disorder characterized by unilateral cerebral malformations and ipsilateral scalp, face, and eye lesions. Distinguishing histopathologic features are dysgenesis and neoplasia of the adipose tissue. A Caucasian boy had soft tumors and elastic papules on his head since birth, associated with atrophic areas, and a bilobed lesion on the upper right eyelid. On the bulbar conjunctiva of the right eye, an oval 6-mm lesion was present. Ultrasonogram, computerized tomographic scan, and magnetic resonance imaging revealed a dilation of the right lateral ventriculus, a mass on the pontocerebellar angle, agenesia of the corpus callosum, an arachnoidal cyst on the right hemisphere, microcalcifications, and pachygyria. The histology of a soft cutaneous tumor was consistent with a fibrolipoma, and dispersed extracellular lipid globules in the upper dermis were found on electron microscopy. The diagnosis suggested by these findings was encephalocraniocutaneous lipomatosis. Even in view of the rarity of the syndrome (11 cases described in the literature), this patient seems unusual because of the bilateral distribution of the cutaneous lesions and because of the agenesia of the corpus callosum. The peculiar ultrastructural findings require further confirmation. PMID- 8346112 TI - Rothmund-Thomson syndrome associated with annular pancreas and duodenal stenosis: a case report. AB - The Rothmund-Thomson syndrome is a rare autosomal recessive condition. It is primarily a clinical diagnosis with manifestations that include poikiloderma, short stature, sparse hair, juvenile cataracts, small hands and feet, bone defects, photosensitivity, hypogonadism, defective dentition, onychodystrophy, and hyperkeratosis. There is only one published case of associated gastrointestinal abnormalities. We report a patient with Rothmund-Thomson syndrome with annular pancreas and duodenal stenosis. PMID- 8346114 TI - Pemphigus neonatorum. AB - The diagnosis of pemphigus neonatorum in an infant girl was based on clinical, histologic, and immunofluorescence evidence. The outcome was benign, and the skin lesions resolved within two weeks. PMID- 8346116 TI - Neonatal lupus erythematosus and maternal lupus erythematosus mimicking HELLP syndrome. AB - A 4-month-old boy had a faint, confluent, macular erythema involving the forehead, nose, and philtrum, and matlike telangiectases over the forehead and eyelids. The clinical features, course, and laboratory studies were characteristic of neonatal lupus erythematosus. He was otherwise healthy and the product of a preterm twin pregnancy complicated by the development of maternal HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. The patient had elevated Ro(SSA) and La(SSB) antibody titers, and studies performed on maternal blood disclosed positive antinuclear antibodies and elevated Ro and La antibody titers. PMID- 8346115 TI - Linear IgA bullous dermatosis in a neonate. AB - A newborn black boy had two facial blisters at birth that progressed to bullous lesions over the trunk, genitals, extremities, and oral and tracheal mucosa. A biopsy specimen demonstrated a subepidermal bulla with mixed eosinophilic and neutrophilic, inflammatory infiltrate. Direct immunofluorescence showed linear IgA, IgG, and C3 depositions along the basement membrane zone, consistent with a diagnosis of childhood linear IgA bullous dermatosis (chronic bullous dermatosis of childhood). The skin disease was controlled with combined prednisone and dapsone. This is the youngest reported patient with the disease. Linear IgA bullous dermatosis should be considered in the differential diagnosis of blistering diseases of the newborn, and immunofluorescence should be performed on a skin biopsy specimen. PMID- 8346117 TI - Congenital platelike osteoma cutis: case report and review of the literature. AB - An 18-year-old girl had a progressive enlarging plate of subcutaneous bone in the scalp since birth. Histologic examination of the lesion showed typical osteoma cutis. There was no history of any skin disease prior to development of the osteoma. Frequently congenital and usually located on the scalp, platelike osteoma is a rare variant of osteoma cutis. PMID- 8346118 TI - Down syndrome, alopecia universalis, and trachyonychia. AB - A 16-year-old boy with Down syndrome and alopecia universalis had dystrophy of all nails. A presumptive diagnosis of tinea unguium, common in persons with Down syndrome, had been made nine years earlier. Despite antifungal therapy, the condition of the nails worsened. We were unable to detect fungi, and believe that his nail changes are most consistent with alopecia-associated trachyonychia (formerly 20-nail dystrophy), a condition not previously reported in persons with Down syndrome. PMID- 8346119 TI - Linear nevus sebaceus of Jadassohn treated with the carbon dioxide laser. AB - A 10-year-old boy from Guiana was born with a linear nevus sebaceus covering his entire nose from the glabella area to the tip. Cosmetic appearance, which was the major concern of the patient and his family, was greatly improved by the use of the carbon dioxide (CO2) laser. The CO2 laser has not been reported previously as a treatment modality for nevus sebaceus. PMID- 8346120 TI - What syndrome is this? Monilethrix syndrome. PMID- 8346121 TI - An 18-month-old boy with a persistent papular eruption. PMID- 8346122 TI - Early-onset nevi. PMID- 8346123 TI - Leucotrichia in nevus depigmentosus. PMID- 8346124 TI - Acute lymphoblastic leukemia associated with dermatomyositis in a child. PMID- 8346125 TI - Nodular prurigo in a child. PMID- 8346126 TI - Topical progesterone as treatment of choice in genital lichen sclerosis et atrophicus in children. PMID- 8346127 TI - Treatment of childhood linear morphea with D-penicillamine. PMID- 8346128 TI - Diagnosis and treatment of digoxin toxicity. PMID- 8346130 TI - Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association. AB - There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest. PMID- 8346131 TI - Clinic blood pressure measurements and blood pressure load in the diagnosis of hypertension. AB - We have retrospectively compared the blood pressure load derived from 24 hour ambulatory blood pressure monitoring in patients with all clinic blood pressure readings elevated with those with only some elevated pressures to establish whether clinic readings alone are good predictors of blood pressure status. Fifty seven patients attending a district general hospital hypertension clinic who were not on anti-hypertensive treatment were selected. Between two and six clinic readings were taken over a period of 1-6 months. Forty out of 57 patients had at least one clinic diastolic blood pressure reading of < 90 mmHg and, of these, 14 (35%) had a high blood pressure load and 26 (65%) had a normal blood pressure load. Patients with all diastolic blood pressure readings > 90 mmHg totalled 17 and of these 11 (65%) had high load and six (35%) had normal load. Patients with clinic diastolic blood pressure > 90 mmHg were significantly more likely to be truly hypertensive on the basis of blood pressure load than if one or more clinic readings was below 90 mmHg (P < 0.05). Diastolic pressures have some predictive power as to the blood pressure status defined by blood pressure load, but even consistently raised diastolic pressures do not necessarily indicate hypertension. Likewise one or more clinic diastolic blood pressure < 90 mmHg does not assuredly indicate normotension. Twenty-four hour ambulatory blood pressure monitoring may have an increasingly important role in the assessment of hypertension. PMID- 8346132 TI - Osteoporosis and the Marfan syndrome. AB - Fourteen patients with Marfan syndrome, defined according to present criteria, had bone mineral content of the distal forearm measured by single photon absorptiometry. Patients were matched for age and sex with a large local group of healthy volunteers. While further work is needed with other methods of densitometry with measurements at other sites, our results provide no evidence that there is an increased incidence of osteoporosis in Marfan syndrome. Previous reports of an association were probably due to incorrect clinical diagnosis or confusion with clinically similar syndromes known to cause osteoporosis. PMID- 8346129 TI - Intensive care. PMID- 8346133 TI - A comparison of 10 MHz ultrasound and 201-thallium/99m-technetium subtraction scanning in primary hyperparathyroidism. AB - Both high resolution (10 MHz) ultrasound and 201-thallium/99m-technetium subtraction scanning (Tl/Tc) were carried out preoperatively in 25 patients with primary hyperparathyroidism. Operative findings were the standard against which these two imaging methodologies were compared. Tl/Tc scanning showed a sensitivity of 42% and a specificity of 97%. By comparison, sensitivity of ultrasound was 38% and specificity 89%. Both techniques were positive together in nine instances and correctly localized the parathyroid adenoma in eight of these. In 44% of cases, however, both methods together failed to localize any abnormal parathyroid tissue. The ability of these modalities to localize abnormal parathyroid tissue correctly tended to vary with gland size. Where both ultrasound and Tl/Tc scans were negative, median gland size was smaller at 170 mg (range 50-2,500 mg), compared with where Tl/Tc scanning was correct (750 mg, 150 6,820 mg; P < 0.03), ultrasound was correct (960 mg, 100-6,820 mg; P < 0.03) and both techniques together were correct (980 mg, 600-6,820 mg; P = 0.002). These results suggest that neither Tl/Tc scanning or ultrasound has sufficient sensitivity or specificity to be used routinely in the preoperative evaluation of patients with primary hyperparathyroidism. PMID- 8346134 TI - Ultrasound-guided needle aspiration of amoebic liver abscess. AB - This prospective study was carried out on 200 patients with clinically, ultrasonographically and serologically confirmed amoebic liver abscess. The role of ultrasound-guided needle aspiration in addition to medications was evaluated compared to drug treatment alone. Both the groups were monitored clinically and sonographically for up to 6 months after diagnosis. The initial response (after 15 days) was better in the aspirated group (P < 0.05) but resolution of abscess after 6 months were similar. There was a more rapid clinical response in the aspirated group, particularly in those with larger (> 6 cm) abscesses and there were no complications. Percutaneous ultrasound-guided needle aspiration is a safe diagnostic and therapeutic approach which enhances clinical recovery, accelerates resolution, especially in large abscesses, and prevents complications. PMID- 8346135 TI - Combined transhepatic and endoscopic procedures in the biliary system. AB - Endoscopic biliary procedures are 89-97% successful in skilled hands. The commonest causes of failure are inability to cannulate the papilla of Vater due to difficult anatomy or tortuosity of the distal common bile duct and failure to cross a rigid biliary stricture. In nearly all of these cases, successful endoscopic procedures can be completed after percutaneous antegrade placement of a small catheter or guidewire to the duodenum. In 44 such combined procedures on 42 patients, the success rate was 43 (98%). There were two severe and eight mild complications. Combined procedures overcome the difficulties caused by tortuous biliary ducts and rigid strictures while obviating the need for more extensive percutaneous procedures and transhepatic tract dilatation. PMID- 8346136 TI - Use of intravenous cannulae by junior hospital doctors. AB - One hundred junior hospital doctors were surveyed to investigate their use of intravenous cannulae. Anaesthetists inserted more cannulae per day than non anaesthetists and were more likely to use local anaesthetic and wear gloves, although most doctors never or rarely did so. Anaesthetists were also more knowledgeable than non-anaesthetists about the sizes of cannulae they used and the sizes available, although there was considerable ignorance overall in this regard. Many doctors regularly place themselves at risk and expose their patients to unnecessary pain during intravenous cannula insertion, and have little knowledge about the cannulae they use. PMID- 8346137 TI - Recurrent confusion and hypopituitarism. AB - Three women in late middle age had recurrent episodes of confusion which could not be explained solely on the basis of an associated infection. All three patients had latent hypopituitarism diagnosed on final presentation. Each patient had a previous history of a severe postpartum haemorrhage followed by two further pregnancies. Experienced clinicians had not made a diagnosis of confusional episodes due to hypopituitary encephalopathy because the history was not immediately available in the confused patient, and the significance of deficient axillary and pubic hair was not given due emphasis. PMID- 8346138 TI - Adrenocorticosteroid deficiency: an unusual cause of fever of unknown origin. AB - We report the case of a lady with multiple presentations and admissions with fever. The eventual diagnosis was made of adrenocorticosteroid deficiency. PMID- 8346139 TI - Significance of a low serum ferritin level in elderly in-patients. AB - Iron deficiency, defined as a serum ferritin level less than or equal to 50 micrograms/l was found in 28 (11%) of 252 consecutive elderly in-patients (mean age 81 years). Sixteen among them were anaemic and only five had a microcytic anaemia. In a separate study, 15 anaemic and 13 non-anaemic iron-deficient elderly in-patients were investigated in order to evaluate the prevalence of gastrointestinal symptoms and lesions in both groups. In nine of the anaemic and seven of the non-anaemic patients a potential cause for the iron deficiency was established. Most anaemic and non-anaemic patients lacked the symptoms described as suggestive of underlying gastrointestinal pathology. Thus, a ferritin level less than or equal to 50 micrograms/l justifies a gastrointestinal investigation if the general condition allows for it as well in anaemic as in non-anaemic elderly hospitalized patients. Therefore, serum ferritin should be part of the routine biochemical investigation of elderly in-patients. PMID- 8346140 TI - Multiple lymphomatous polyposis and the role of fine needle aspiration cytology. AB - Multiple lymphomatous polyposis is an uncommon but distinctive form of gastrointestinal lymphoma. Clinical symptoms may closely resemble those of colorectal carcinoma and diagnostic confusion may result. The condition has a characteristic pathological appearance and immunophenotype which is important in allowing distinction from other less aggressive forms of gastrointestinal lymphoma. We report a case of this unusual condition in which the diagnosis was aided by fine needle aspiration cytology. PMID- 8346141 TI - Pyrexia of unknown origin in association with bladder diverticulum tumour. AB - A case of pyrexia due to a rapidly growing undifferentiated transitional cell carcinoma in a bladder diverticulum is described. The literature is reviewed and the causes of pyrexia associated with neoplasia briefly discussed. PMID- 8346143 TI - Parathyroid crisis and acute viral hepatitis B infection. AB - The simultaneous development of acute hyperparathyroidism and viral hepatitis B infection in a 72 year old male is described. Resolution of the hepatitis was accompanied by improvement in the parathyroid hormone mediated hypercalcaemia. It is postulated that antibodies to the hepatitis B virus may have altered the calcium 'set point' allowing uncontrolled synthesis and release of parathyroid hormone during the acute illness. PMID- 8346144 TI - Bot-fly bite. PMID- 8346142 TI - Invasive aspergillosis in two patients with acute lymphoblastic leukaemia in complete remission. AB - Invasive aspergillosis is a disease of the immunosuppressed patient. We describe two patients with acute lymphoblastic leukaemia who attained complete remission, with partial or complete bone marrow recovery, but who went on to develop fatal invasive aspergillosis contemporaneous with recovery of neutrophil counts. Quantitative recovery of peripheral blood neutrophil counts does not guarantee control of Aspergillus infection, perhaps due to functional neutrophil deficiencies post-chemotherapy, and specific defensive strategies adopted by the organism itself. PMID- 8346145 TI - Primary tuberculous appendicitis. PMID- 8346146 TI - An unusual cause of biliary peritonitis. PMID- 8346147 TI - Atypical manifestations of ruptured abdominal aortic aneurysms. PMID- 8346148 TI - Effects of different floor types and levels of washing of waterers on broiler performance and bacteria count of drinking water. AB - The objective of the present experiment was to determine the effect of different flooring materials and washing of waterers on broiler performance. The floor treatments were 1) black, plastic-coated expanded metal, relatively rigid (B); 2) white plastic, semi-rigid, with rectangular openings (WR); 3) white plastic, semi rigid, with square openings (WS); and 4) 3 cm of rice hull litter (C). One hanging waterer was placed in each pen. Wash treatments were 1) trough and bell washed every Monday, Wednesday, and Friday (AW); 2) wash trough only on Monday, Wednesday, and Friday (TW); and 3) the waterers were never washed after the 2nd wk (NW). Broilers reared on C has significantly lower BW than those broilers on B floors. Broilers reared on the B and WS floors had significantly higher breast blister scores and percentage of birds with blisters than broilers reared on C floors. Broilers reared on C had lower enlarged feather follicle scores than those reared on all raised floors and a lower percentage of enlarged feather follicles than those broilers reared on WS or WR floors. Broilers reared on WS+TW had significantly better feed conversion than WS+AW, B+TW, and B+AW treatments. Broilers reared on WR+TW treatment were significantly higher in breast blister score than broilers reared on WR+AW, C+TW, and C+AW treatments. Broilers reared on C+TW and C+AW treatments were significantly lower in breast blister score except for broilers reared on C+NW, WR+AW, and WS+AW treatments. Broilers reared on C+NW treatment were significantly lower in enlarged feather follicle score than those broilers reared on B+TW, WR+AW, and WS+NW treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346149 TI - Behavioral responses of broiler chickens to handling: effects of dietary tryptophan and two lighting regimens. AB - In three 2 x 2 factorial experiments, effects of added dietary Trp (0 or .2%, Experiments 1 and 2; 0 or .4%, Experiment 3) and two lighting regimens [1) constant 23-h photoperiod (23H); or 2) increasing photoperiod (INC)] on behavioral responses of broilers to handling were assessed. In Week 6 of Experiment 1, and Weeks 3 and 6 of Experiments 2 and 3, 32 chickens from each treatment were picked up and held by both legs for 30 s, carried for 60 s, and induced into tonic immobility (TI). In all experiments, chickens reared under INC were more likely to flap when carried, and flapped longer, than chickens reared under 23H (P < .01). In Experiments 2 and 3, INC chickens were more likely to curl the body ventrally when handled and were more susceptible to TI induction than 23H chickens (P < .05). The duration of TI was shorter on INC than 23H in Experiment 2 (P < .05), and longer in Experiment 3 (P < .001). Dietary Trp supplementation resulted in a lower flapping duration and higher incidence of body curling in Experiment 2 (P < .05), and a shorter TI duration in Experiment 3 (P < .05). Flapping, body curling, and TI responses of chickens varied between handlers (P < .05). Vocalization and flapping rates were lower, and flapping incidence and duration of flapping and TI higher, in Week 6 than in Week 3 (P < .05). Chickens reared under INC may be at greater risk of injury during preslaughter handling than chickens reared under 23H.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346150 TI - Liquid methionine hydroxy analog (free acid) and DL-methionine attenuate calcium induced kidney damage in domestic fowl. AB - To evaluate the possibility that kidney damage may be induced by the commercial practice of feeding high-Ca (HCa) prelayer rations, and to evaluate the protective efficacy of supplementing HCa diets with liquid methionine hydroxy analog free acid or DL-methionine, 12-wk-old female Single Comb White Leghorn pullets were fed one of the following corn-soybean meal-based diets until they reached 22 wk of age: normal-Ca (NC, 1% Ca); HCa (HC, 3.5% Ca); HCa supplemented with .34 or .68% liquid methionine hydroxy analog free acid (HC3A or HC6A); or HCa supplemented with .3 or .6% DL-methionine (HC3DL or HC6DL). The unsupplemented HC diet caused a significant reduction in kidney mass and a significant increase in the incidence of gross kidney damage and urolithiasis in pullets necropsied at 22 wk of age. Calcium-induced kidney damage was attenuated in a dose-response fashion by supplementing the HC diet with liquid methionine hydroxy analog and DL-methionine. None of the diets caused a significant metabolic acidosis. Plasma uric acid concentrations were not predictive of the extent of Ca-induced kidney damage. Analyses of glomerular size distributions indicated that subclinical or "hidden" kidney damage may not progressively develop into urolithiasis as hens mature. When compared with hens reared on the NC diet, rearing hens on the HC, HC3A, HC3DL, HC6A, or HC6DL diets did not consistently affect hen-day egg production, egg mass, eggshell mass, percentage eggshell, or bone mineralization. PMID- 8346151 TI - Bursal secretory dendritic-like cell: a microenvironment issue. AB - In 1978, Olah and Glick identified in the medulla of the bursa of Fabricius a dendritic cell, the bursal secretory dendritic-like cell (BSDC). The morphology of BSDC, the functional relationship of BSDC to bursal follicle development and the spleen, and the identification in the embryo of the BSDC precursor was reported. The precursor BSDC appeared in the bursa before B cells. A monoclonal antibody to vimentin, an intermediate filament, will identify BSDC and not B cells in posthatch chickens. The vimentin-positive cells, but not B cells, in hatched chicks express complete IgG chain. Taken together, the present data may contribute to the events occurring during the bursal-dependent stages of B cell development. Immunoglobulin gene rearrangement, within the bursa or at extra bursal sites, and clonal expansion at extra-bursal sites are antigen-independent and dependent, respectively. The bursal-dependent stage includes the expansion of the Ig rearranged cells and gene conversion, which contributes to antibody diversity. The IgG and granular products produced by BSDC may act as ligand and signals for B cell expansion and gene conversion. PMID- 8346152 TI - Plasma cells of the chicken Harderian gland. AB - The chicken Harderian gland (HG) is densely populated in its subepithelial spaces with plasma cells (PC). These immune cells produce and secrete Ig of the IgA, IgG, and IgM classes. Such Ig secretion into the tears affords the upper respiratory tract with protective antibodies. The immunological role of the HG is quite interesting; yet this gland is a site of unusual PC proliferation. Studies of the gland utilizing bromodeoxyuridine (BrdUrd) incorporation into DNA and propidium iodide (PI) staining of PC DNA have verified previous suggestions in the literature that PC of the chicken HG proliferate. Both isolated PC suspensions and frozen sections of the HG from chicks aged 6 to 9 wk reveal that BrdUrd is incorporated into PC DNA. Furthermore, flow cytometric analysis of PI stained PC indicates a relatively high percentage of PC in S phase of the cell cycle. Continued studies are examining possible mechanisms controlling proliferation and differentiation of PC in the HG. It is believed that the stromal elements of the HG produce and secrete a factor(s) that influences PC proliferation and differentiation. Isolation and characterization of this influencing factor(s) will allow for the possible systemic application of the factor(s) for enhancement of immune responses. PMID- 8346153 TI - Avian macrophages: contribution to cellular microenvironment and changes in effector functions following activation. AB - The capacity of macrophages to generate metabolites and monokines having effector and regulatory functions can result in a major impact on their cellular microenvironment. Macrophage products synthesized in response to bacterial lipopolysaccharide stimulation include reactive oxygen and nitrogen intermediates as well as tumor necrosis factor (TNF). These secreted products of macrophages exhibit bioactivity either locally or systemically. Although the mechanism of action of avian monokines such as TNF-like factor may be similar to their mammalian counterparts, chicken TNF seems to lyse cells of chicken origin and not of mammalian origin. Furthermore, the generation and activity of products such as TNF is directly influenced by environmental stressors such as heat and toxins. PMID- 8346154 TI - Biogenic amines regulate avian immunity. AB - Alzet mini-osmotic pumps were implanted subcutaneously to administer norepinephrine (NE) and epinephrine (E) to 6-wk-old line UNH 105 chickens. Dose time studies showed the most effective NE and E dose and exposure time on two chicken cellular immune responses: the phytohemagglutinin (PHA) wattle response and leukocyte migration. Administration of 1 microgram/h NE for 72 h suppressed significantly the wattle stimulation index [2.48 +/- .3 (SE)] compared to that of saline controls (4.1 +/- .3) but enhanced mean leukocyte migration (7.7 +/- .3 versus 4.9 +/- .3). Epinephrine at 1 microgram/h for 72 h significantly suppressed the wattle index (1.8 +/- .2) compared to that of controls (2.8 +/- .3) but E at 1 microgram/h for 48 h enhanced leukocyte migration (9.5 +/- .2 versus 6.4 +/- .2). Continuous administration of NE and E at physiological levels alters cell-mediated immunity and appears to have an immune regulatory role in the chicken. PMID- 8346155 TI - The humoral activity of the avian thymic microenvironment. AB - The thymic microenvironment (composed of the lymphoepithelial stroma and the secretory products of the thymic epithelium) provides the required milieu for the development of the thymus-derived lymphocytes (T cells). There is limited information characterizing or identifying the active secretory components of the avian thymus. The work discussed here has focused on examination of the presence, regulation, and activity of one of the thymic hormones (thymulin) in the chicken. A thymulin-like product has been shown to exist in chicken serum as assessed by the mammalian bioassay and an ELISA immunoassay; thymectomy removes this product from the serum. Serum thymulin activity has been shown to be directly related to the thyroid status of the chick with the functionally hypothyroid Cornell sex linked dwarf strain having lower levels than the euthyroid K strain. Alterations in circulating thymulin concentrations produced by daily thymulin injections resulted in an altered profile of the major peripheral blood T cell subpopulations and produced significant changes in the autoimmune pathology present within the Obese strain chicken. These approaches represent preliminary attempts to study the role of thymulin in avian immune development and in immune neuroendocrine interactions. PMID- 8346156 TI - Immune modulation by altered nutrient metabolism: nutritional control of immune induced growth depression. AB - The ability of conjugated isomers of linoleic acid (CLA) to prevent reduced growth rate following endotoxin (lipopolysaccharide, LPS) injection was studied in two chick trials and one rat trial. Chicks (10 per treatment) were fed a corn and soybean meal-based diet with or without .5% CLA. At 21 days of age, chicks were weighed and injected i.p. with 1 mg/kg BW Escherichia coli LPS and sterile PBS. Body weights were again determined 24 h later. Antibody responses to SRBC were also determined. Rats fed .5% stearic acid or CLA for 4 wk (seven per treatment) were also injected with LPS, and BW change over a 24-h postinjection period was determined. Antibody responses to BSA, phytohemagglutinin foot pad swelling, and phagocytosis of elicited peritoneal macrophages were also determined. The CLA had no adverse effects on any immune variables measured in the chicks and rats. The CLA enhanced the phytohemagglutinin response and macrophage phagocytosis in rats. Chicks fed CLA and injected with LPS continued to grow, whereas those not fed CLA either failed to grow or lost weight following LPS injection. Both control and CLA-fed rats lost weight over the 24-h period after LPS injection; however, the loss of weight in rats fed CLA was only half of the weight loss of the control rats. Thus, CLA is effective in preventing the catabolic effects of immune stimulation. PMID- 8346157 TI - Avian gut-associated immune system: implication in coccidial vaccine development. AB - Host responses to coccidia are complex and involve both humoral and cellular immune mechanisms. Convincing evidence exists for a major role of cell-mediated immunity in anticoccidial resistance. With an increasing need for the development of coccidial vaccine, understanding of the intestinal immune system is crucial. To provide increased insight into the immune mechanisms involving mucosal immune response to coccidia, cellular events involved in the maturation of intestinal immune system were studied. Postnatal development of various T lymphocyte subpopulations expressing CD3, CD8, CD4, and antigen-specific T cell receptor (TCR) heterodimers expressing gamma delta (TCR1) or alpha beta (TCR2) was investigated in chickens. Intraepithelial lymphocytes (IEL) expressing the CD8 antigen increased gradually following hatching and subsequently declined with age. The CD4+ cells represented a minor subpopulation among the IEL. The ratios of IEL T cells expressing gamma delta (TCR1) or alpha beta (TCR2) in the intraepithelium of chickens gradually increased after hatching. These results indicate maturational changes of intestinal immune system that should be considered in the development of vaccine against coccidia. PMID- 8346158 TI - Relative bioavailability of L-ascorbyl-2-polyphosphate in broiler chickens. AB - Broiler chick diets and drinking water were supplemented with two sources of vitamin C: crystalline L-ascorbic acid (AsA) or L-ascorbyl-2-polyphosphate (APP) to provide 0, 25, 50, 100, 200, 400, 800, 1,600, and 3,200 ppm (mg/kg) AsA. The bioavailability of APP relative to AsA, as estimated by the change in plasma AsA concentration, was evaluated during 24-h periods of supplementation. When provided in the feed, no differences in dietary AsA content were attributed to vitamin source. In contrast, APP administration at 25 and 50 ppm, resulted in higher (P < .001) AsA values in drinking water when compared with AsA supplementation. Plasma AsA values were elevated (P < .05) above baseline when either AsA or APP were supplemented in the feed or water at a level of 400 ppm or greater. Plasma AsA concentrations, following supplementation of the diets, were higher (P < .05) in AsA-treated (800 ppm) chicks when compared with APP supplemented chicks. During water supplementation, AsA (800 ppm) and APP (3,200 ppm) administration resulted in higher plasma AsA values when compared with their alternate vitamin source. At all other levels of water supplementation, no differences in plasma AsA were associated with vitamin source. The absence of a consistent difference in plasma AsA, relative to vitamin source, suggests that the isolated differences observed may be due to chance. It was concluded that APP was of similar bioavailability to that of AsA, as estimated by the ability to elevate plasma AsA concentrations in broiler chicks. PMID- 8346160 TI - Treatment of osteoporosis. PMID- 8346159 TI - Carotid endarterectomy for TIAs. PMID- 8346161 TI - Long-term management. PMID- 8346162 TI - The final hurdle. PMID- 8346163 TI - Management of gout. PMID- 8346164 TI - Disorders of calcium metabolism. PMID- 8346165 TI - The menarche. PMID- 8346166 TI - Growth problems. PMID- 8346167 TI - Screening for metabolic disorders. PMID- 8346168 TI - Management of hypercholesterolaemia. PMID- 8346169 TI - Prescribing in the elderly. PMID- 8346170 TI - The "cause of death" is dying. PMID- 8346171 TI - Diffuse alveolar damage and acute interstitial pneumonitis: histochemical evaluation with lectins and monoclonal antibodies against surfactant apoprotein and collagen type IV. AB - Diffuse alveolar damage (DAD) and acute interstitial pneumonitis (AIP) often present clinically as the adult respiratory distress syndrome. To evaluate the usefulness of histochemical techniques and to better understand the histopathologic changes of these diffuse lung injuries, postmortem lung sections of 14 and 33 patients who had been diagnosed as having DAD in organizing stage and AIP, respectively, were studied with the use of lectins and monoclonal antibodies against surfactant apoprotein (PE-10) and collagen type IV. On hematoxylin-eosin stained sections, type II pneumocyte hyperplasia and hyaline membrane formation were the major histopathologic findings in both DAD and AIP. The binding rates of type II pneumocytes to Ulex europaeus agglutinin I (UEA-I) in both DAD (64%) and AIP (45%) cases were significantly higher than those of type I pneumocytes or alveolar macrophages (both P < 0.001). Reactions of type II pneumocytes to PE-10 varied from 40 to 44% in DAD and 0 to 100% in AIP cases depending on the use of respirator and steroid medication. Therefore, it may be said that UEA-I and PE-10 are useful methods for outlining hyperplastic type II pneumocytes in both DAD and AIP. Hyaline membrane coating alveolar septal surfaces and exudate in alveolar air spaces were also stainable with PE-10. Surfactant apoprotein remained demonstrable histochemically within type II pneumocytes and hyaline membrane despite severe inflammatory injuries of the lungs. The immunohistochemical stain using anti-collagen type IV antibody revealed discontinuous alveolar basement membrane in 50% of DAD patients with respirator use and 80% of AIP patients with steroid medication. PMID- 8346172 TI - Membranous glomerulonephritis (MGN) in transplanted kidneys: morphologic investigation on 256 renal allografts. AB - Twenty-two cases of membraneous glomerulonephritis (MGN) were identified among 256 bioptically investigated transplanted patients. MGN was defined as de novo in 15 patients and recurrent in three. The type of MGN could not be ascertained with certainty in the other four. Several morphologic features unusual for the idiopathic form of MGN were found. Most cases disclosed focal segmental distribution of subepithelial deposits and showed the contemporaneous presence of different stages of the disease according to Ehrenreich and Churg classification. In addition mild-to-moderate mesangial cell proliferation was found in about one third of de novo MGN biopsies. Endocapillary hypercellularity was observed in 14 specimens and held to be due to an excess of mononuclear blood cells, related to a concomitant episode of rejection. Chronic transplant glomerulopathy was found in 47% of patients with de novo MGN and in 66% of those with recurrent MGN, being more frequently observed in specimens with diffuse distribution of deposits. Repeated biopsies showed progression of the stage and extension of deposits to a large number of capillary loops in four out of six patients. De novo MGN was documented 1 to 54 mo (mean value 20.2 mo) after transplantation, and the recurrence was observed after 12, 15, and 42 mo. All but two patients (who were anuric) complained of proteinuria, which was in the nephrotic range in 12. Apart from the significantly higher frequency in de novo MGN patients of DR4 antigen, whose significance must in any case be re-evaluated in a larger series, none of the factors so far suggested to be linked to the onset of de novo MGN has found further support in our study. On the contrary, relevance in favoring the appearance and the evolution of MGN has to be attributed to transplant glomerulopathy, which, moreover, seems to be more important than MGN itself in causing the unfavorable outcome of the graft. PMID- 8346173 TI - Expert systems as an aid for the pathologist's role of clinical consultant: CANCER-STAGE. AB - The traditional role of the pathologist as a clinical consultant for various clinical specialists has become more difficult with the explosion of information that has taken place in the past decades. Rule-based expert systems offer the ability to store and quickly and efficiently retrieve information that is relevant to specific clinical situations. They are ideally suited for simple repetitive tasks such as the staging of patients with cancer and the retrieval of therapeutic and prognostic information. A microcomputer-based expert system, CANCER-STAGE, is described that allows a pathologist to perform these tasks with minimal computer training. The system was constructed by utilizing an inexpensive expert system development package (EXSYS). The knowledge base from the literature is stored in 370 IF-THEN rules that have notes with therapeutic information and references. The computer user interacting with the system answers questions and is quickly provided with the TNM stage of a particular patient and a short summary with therapeutic options. The conditions can be changed and the results of various WHAT-IF simulations compared for educational purposes. PMID- 8346174 TI - Image analysis versus flow cytometry for DNA ploidy quantitation of solid tumors: a comparison of six methods of sample preparation. AB - With the availability of user-friendly interactive image analysis instruments for DNA analysis, there is a growing need for comparison with the established methodology of flow cytometry. We have compared the results of DNA ploidy quantitation in 12 solid tumors prepared by six different techniques of sample preparation: flow cytometry of fresh cell suspensions and of nuclei isolated from formalin-fixed, paraffin-embedded tissue; and image analysis of touch preparations, of disaggregated cells from paraffin-embedded tissue as well as of 3- and 7-microns-thick tissue sections. Complete agreement in DNA ploidy results obtained by the six methods was found in six out of 12 solid tumors. Image analysis of touch preparations detected most tetraploid and multiple aneuploid peaks. Sections of 7-microns-thick tissue gave better histogram quality than 3 microns-thick sections, however tetraploid peaks were not resolved in one case. Image analysis of disaggregated paraffin-embedded tumor showed comparable ploidy to fresh touch preparations in seven out of 12 cases, the discrepancies being due to loss of tetraploid or multiple aneuploid peaks. Flow cytometry gave good histograms, but tetraploid and multiple aneuploid peaks were occasionally not detected. Each method presents advantages and disadvantages. Flow cytometry and image analysis are complementary methods for DNA quantitation, and more than one method may be necessary to confirm the DNA content of solid tumors. PMID- 8346175 TI - Adhesion onto and invasion into mammalian cells by mycoplasma penetrans: a newly isolated mycoplasma from patients with AIDS. AB - The newly identified mycoplasma, Mycoplasma pentrans shows remarkable pathobiologic properties: it adheres to cell surfaces, deeply penetrates into the cell, strongly hemadsorbs human red blood cells, and cytadsorbs human CD4+ lymphocytes and monocytes. These in vitro biologic activities of mycoplasmas have been previously shown to be associated with pathogenic virulence in vivo. Both adhesion and invasion clearly involve the organism's unique tip-like structure. Invading mycoplasmas often have their tip-like structure deeply buried in the cytoplasm of infected mammalian cells. Extensive invasion of the mycoplasma into the cytoplasm may kill the cells. The same pathobiologic processes of adhesion and invasion using the specialized tip-like structure are found on the epithelium in the patient's urogenital tract infected by M. penetrans. Both in vitro and in vivo findings suggest a possible pathogenic role of this newly discovered human mycoplasma and call for careful evaluation of its role in human diseases. PMID- 8346176 TI - Changes in the gastric mucosa following eradication of Helicobacter pylori. AB - Although most studies reporting on the examination of Helicobacter pylori infection have focused on the clearance of the bacteria and the rapid disappearance of the neutrophil infiltrates, the evolution of inflammatory and architectural changes in the antral and corporal mucosa following the eradication of H. pylori has not been addressed systematically. This study examines in detail the histopathologic appearance of the antral and corporal mucosa in a group of patients infected with H. pylori and follows the spectrum of morphologic changes in each of them after the eradication of the infection. At least 11 biopsies ("gastric mapping") were obtained from the antrum and body of each of 15 patients with H. pylori. Complete mapping was then repeated 1, 4, and 10 to 12 mo after the eradication of H. pylori by a course of "triple therapy." Each biopsy was assessed in a semi-quantitative fashion for presence of H. pylori, neutrophils, eosinophils, lymphocytes, lymphoid follicles, and intestinal metaplasia. Other features (integrity of surface epithelium, architecture, fibrosis) were evaluated descriptively. Results were compared with those obtained from a control group of 16 uninfected, healthy adult volunteers. H. pylori infection was eradicated in 11 subjects. The disappearance of neutrophils and the normalization of the surface epithelium closely paralleled that of H. pylori. Persistence of even small numbers of neutrophils was a predictor of relapse. Eosinophils and lymphocytes decreased slowly and did not return to normal levels within 1 yr. Lymphoid follicles decreased very slowly in all patients but were still present in all gastric locations at one year after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346177 TI - An immunophenotypic study of the inflammatory cell populations in colon adenomas and carcinomas. AB - There is increasing interest in the host immunologic response to colon carcinoma as immunotherapeutic techniques are being developed. We studied the inflammatory cells in 27 specimens of normal mucosa, 16 hyperplastic polyps, 21 tubular adenomas, 19 tubulovillous adenomas, 12 villous adenomas, and 17 invasive carcinomas using immunohistochemical techniques in paraffin-embedded tissue. UCHL 1-positive T-cells predominated in the lamina propria of all specimens. In polyps and carcinomas, reactive lymphoid follicles composed of L26-positive B-cells, and UCHL-1-positive T-cells were a prominent feature and UCHL-1-positive cells were increased in the epithelial compartment. Cells bearing surface immunoglobulins were widely distributed in all specimens, with IgA predominating. There was a relative increase in IgG-positive cells in the carcinomas. KP1-positive macrophages, S-100-positive dendritic cells, and HLA-DR-positive cells were oriented toward the lumenal surface in normal mucosa and hyperplastic polyps, suggesting a diffuse antigen presenting system. Macrophages and dendritic cells were increased and dispersed in the neoplasms. HLA-DR expression was increased in the neoplasms, mainly in the stromal cells. We conclude that there is an activated immune response in adenomas and carcinomas of the colon compared to normal mucosa. This is represented by expansion and reorganization of both the T- and B-cell compartments and the macrophage-cell systems. PMID- 8346178 TI - Immunohistologic evaluation of invasion-associated proteases in breast carcinoma. AB - Immunostaining of two invasion-associated proteolytic enzymes, cathepsin D (CD) and urokinase-type plasminogen activator (uPA), was assessed in cryostat sections of 86 stage-heterogeneous breast carcinomas using monoclonal antibodies. Most tumors displayed a focal and/or heterogeneous staining pattern. Overall, staining was more frequent in host-derived stromal and inflammatory cells (uPA 54%, CD 89%) than neoplastic epithelium per se (uPA 24%, CD 70%). Intense (i.e., 2+) stromal, but not neoplastic, CD was significantly correlated with nodal or systematic metastases (node negative--10% versus node positive/systemic--33%, p = 0.04). Further, cumulative staining of more than one enzyme (CD + uPA) or more than one tumor component (stroma + epithelium) correlated with metastatic disease (no metastases--35% versus metastatic--72%, p = 0.005). Neither stromal nor epithelial CD alone was significantly correlated with short-term recurrence free survival, however additive CD staining (i.e., stromal + epithelial) was strongly predictive, overall (both + -75% recurred versus both weak/negative--16% recurred, p = 0.0004) and in node positive patients (p = 0.02). We conclude that (a) enzymes putatively mediating extracellular matrix dissolution may be derived from multiple sources and (b) the metastatic capacity and/or clinical aggressiveness of breast carcinomas may reflect overall proteolytic enzyme expression, suggesting that cooperative enzyme interaction may be required for invasive growth and/or metastasis. PMID- 8346179 TI - The immunopathology and clinical relevance of lymphocyte cultures in liver transplantation. AB - Lymphocytes infiltrating human liver allograft biopsies were expanded in vitro for 3 to 5 days in recombinant IL-2 and then uniformly quantified and phenotypically characterized. The extent of proliferation was correlated with the degree and pattern of lymphocyte infiltration of the source biopsy as well as with the subsequent clinical outcome. Each of the 117 cases was assigned to one of three primary clinical outcome groups based on a retrospective evaluation of the clinical course before and after biopsy. The groups consisted of cases involving viral infection (n = 21), rejection (n = 40), or nonrejection-related allograft dysfunction (n = 56). The rejection group showed significantly greater in vitro expansion of lymphocytes (4201 +/- 685) compared to the nonrejection group (2720 +/- 408, P < 0.05). However, cases from the viral infection group showed the highest overall average lymphocyte growth (6655 +/- 2595, P < 0.05). Immunohistologic evaluation of the source liver transplant biopsy demonstrated increased T-cell infiltration of portal triads primarily by CD8+ T-cells in rejection compared to nonrejection cases (semiquantitative grade 1.3 +/- 0.1 versus 1.0 +/- 0.1, P < 0.05). The viral infection group demonstrated more significant T-cell infiltration (again predominantly CD8+) of the lobules compared to cases without viral infection (1.9 +/- 0.3 versus 1.3 +/- 0.1, P < 0.05). Immunohistologic evaluation of the cultured lymphocytes from the biopsies demonstrated a marked predominance (75% of cultures) of CD8+ T-cells compared to CD4+ T-cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346180 TI - Immunohistochemical profile and differential diagnosis of microglandular adenosis. AB - Twelve examples of microglandular adenosis (MA) were evaluated immunohistochemically using a panel of antibodies directed against actin, S-100 protein, collagen type IV, the c-erb-B2 gene product, and the progesterone receptor, as well as antibodies BER-EP4 and B72.3. The results were compared with the reactions observed in 15 cases of tubular carcinoma and 11 examples of sclerosing adenosis. Three examples of secretory adenosis were also evaluated, but only for S-100 protein and actin. The results confirmed the absence of a myoepithelial cell layer and the presence of basal laminar investiture in MA. Tubular carcinoma lacked a myoepithelial cell layer and basal laminar investiture. Sclerosing adenosis, in contrast, had both a myoepithelial cell layer and displayed basement membrane around the tubules. Secretory adenosis also had a myoepithelial cell layer; the presence of basement membrane could be confirmed easily using periodic acid-Schiff reaction in the three cases of secretory adenosis. An interesting and unexpected finding was the presence of an intensely positive reaction in the epithelial lining cells of the tubules in microglandular adenosis for S-100 protein. A far less intense positivity for S 100 protein was observed sporadically in many normal myoepithelial and some epithelial cells in the adjacent breast lobules. The intensely positive reaction suggests that the proliferating cells in MA correspond to an S-100-positive epithelial cell type that is often present in a small number and in a sporadic manner in the normal breast. The epithelial cells in tubular carcinoma, sclerosing and secretory adenosis were negative for S-100 protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346181 TI - HLA-DR expression in bile duct damage in hepatitis C. AB - Several investigations have demonstrated aberrant expression of HLA-DR on damaged bile duct epithelium of patients with primary biliary cirrhosis, liver allograft rejection, graft versus host disease, and AIDS. Since bile duct damage is a prominent feature of chronic hepatitis C, it may also be associated with HLA-DR induction. Therefore, we examined the expression of HLA-DR antigen in formalin fixed, paraffin-embedded liver biopsy sections of 30 patients with chronic hepatitis C by the avidin-biotin peroxidase complex method using a monoclonal antibody to HLA-DR. HLA-DR was not detected on bile duct epithelium in any of the cases, although bile duct damage of varying degree was observed in 90% of the cases. HLA-DR was expressed by Kupffer cells; inflammatory infiltrates in portal tracts, and in areas of piecemeal necrosis and lobular necrosis; dendritic cells in portal and periportal areas; and occasionally hepatocytes. These observations suggest that the mechanism of bile duct injury in chronic hepatitis C may be different from that of other conditions such as primary biliary cirrhosis, liver allograft rejection, and graft versus host disease. PMID- 8346182 TI - Mucoid vasculopathy: vascular lesions in an autopsy study. AB - Mucoid vasculopathy is a unique, idiopathic, vascular entity observed in autopsy material at the Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India. The vascular lesions are the most prominent manifestation of a pathologic condition characterized by a generalized mucopolysaccharidosis of connective tissues found, for example, within nerve bundles in the adventitia of blood vessels and in the interstitium of such organs as the heart, lung, and kidney. Tissue deposits are accompanied by a mastocytosis. The pathology of vascular lesions observed in 44% of 131 autopsies is described. In this group, mucoid vasculopathy occurred more commonly in young males of lower socioeconomic status. Both arteries and veins are affected, particularly muscular arteries. They present a uniform concentric thickening of the intima and media, causing an apparent reduction in luminal diameter. Significant histological features include (a) large quantities of glycosaminoglycans accompanied by smooth muscle hyperplasia in the intima and media and (b) degenerative changes with mineralization of the internal elastic lamina of arteries and of mucoid material in the media. Except for the mucoid arteriopathy described in popliteal vessels in cases of idiopathic peripheral gangrene from Central Africa, which mucoid vasculopathy resembles somewhat, the latter condition is not exactly comparable to any other known vascular or connective tissue disorder. PMID- 8346183 TI - Cytogenetic and ploidy analysis of prostatic adenocarcinoma. AB - The cytogenetic evaluation of prostatic adenocarcinoma has shown no consistent cytogenetic abnormalities. Despite manipulation of culture conditions, the majority of low-stage, untreated prostatic adenocarcinomas show a normal karyotype. We have performed cytogenetic analysis on eight primary prostate adenocarcinomas, using several control measures to increase the probability that any normal karyotype was derived from neoplastic cells rather than accompanying normal cells. Tumors were grown in media that encourages epithelial growth; DNA ploidy studies were performed before and after tissue culture; and immunohistochemical confirmation of the prostatic and epithelial nature of the cells was done following culture. Percentage of tumor on tissue sections adjacent to those submitted for culture was > 75% in all cases. Seven of eight cases were evaluable, and six cases showed no clonal abnormalities and were diploid. One tumor showed a population of tetraploid cells, without structural abnormalities. Three additional tumors showed evidence of tetraploidy by DNA analysis. One case showed nonclonal marker chromosomes and was aneuploid. This patient was pathologic Stage D. We conclude that the majority of prostatic adenocarcinomas at their inception may not show routinely detectable cytogenetic abnormalities. However, tetraploidy may play a role in the evolution of prostatic adenocarcinoma. PMID- 8346184 TI - Application of flow cytometry in diagnosis of hydatidiform moles. AB - We analyzed the nuclear DNA content of 219 hydropic placentas and 68 control (nonhydropic) placentas by flow cytometry (FCM) using formalin-fixed paraffin embedded tissues. Of 129 cases originally diagnosed as complete hydatidiform mole (CM), 91 were diploid, 25 tetraploid, one triploid, and 12 aneuploid. Of five invasive CM, two were diploid, and three (including one metastasizing mole) were tetraploid. Of 49 partial hydatidiform moles (PM), 36 were triploid and 13 were diploid. Of 41 hydropic abortuses (HA), 34 were diploid, one tetraploid, four triploid, and two aneuploid. Three control placentas were triploid, and the remaining 65 placentas were diploid. Based on FCM and review of the histology, 10 PM were reclassified as HA, and one PM was revised as CM. Four HA were reclassified as PM. One CM was revised as PM. These results show that the difficulty of histologic diagnosis of gestational trophoblastic diseases may lie in PM. Clinical follow-up information was available in 51 CM and 20 PM, and persistent trophoblastic disease followed 18% of CM and 0% of PM. Among diploid complete moles, DNA ploidy did not associate with persistent disease. A significant increase S-phase fraction (SPF) was detected in diploid CM when compared with HA and control placentas. However, among diploid CM, there was no significant difference of SPF between those with and without persistent disease. These findings suggest that DNA measurements by FCM may be an important aid in the diagnosis of hydropic placentas, but not a useful tool for predicting persistent disease. PMID- 8346185 TI - Proliferation of dendritic cells in the bronchioles of sudden infant death syndrome victims. AB - Sudden Infant Death Syndrome (SIDS) victims have significantly thickened bronchiolar walls with increased mononuclear cells in the adventitia. An immunohistochemical study was performed on 25 SIDS and 18 aged-matched control infants to characterize these cells. The panel of antibodies included alpha-1 antitrypsin, lysozyme, actin, vimentin, Leu M1, NSE, S-100, Leu 6, bombesin, serotonin, anti-substance P, vasoactive intestinal peptide, MAC 387, and Factor XIIIa. The bronchiolar cells stained with S-100 antibody and demonstrated slender processes similar to dendritic cells, such as Langerhans' cells, and interdigitating reticulum cells, present in normal tissues as well as in certain tumors and inflammatory diseases. Manual counting of the S-100 positive cells and fibers revealed both of these to be significantly increased in SIDS infants as compared to age-matched control infants. Morphologically, the bronchiolar dendritic cells closely resembled Langerhans' cells and therefore may have similar immunologic functions, such as antigen presentation and viral and neoantigen immunosurveillance. We hypothesize that the proliferation of these dendritic cells in SIDS victims is a result of exposure to environmental antigens, resulting in a thickening of the bronchiolar walls, narrowing of the lumen, and reduction in airflow, thus causing a chronic or persistent hypoxia. PMID- 8346186 TI - Evaluation of prognostic indicators in squamous carcinoma of the vulva including nuclear DNA content. AB - The prognostic value of clinical and pathologic features including tumor ploidy status was evaluated in 43 randomly selected primary invasive squamous carcinomas of the vulva in which the lesion was totally excised and a lymph node dissection performed. By both univariate and multivariate analysis, survival most closely correlated with the number of involved lymph nodes. In the subgroup of patients with negative lymph node dissections, outcome was also found to correlate with tumor diameter but not with any other feature studied including nuclear DNA content. Both the FIGO surgical staging system and stratification of patients by Gynecologic Oncology Group (GOG) risk groups provided valuable methods of estimating prognosis with survival rates of 100%, 80%, 59%, and 25% for FIGO stages I, II, III, and IV, respectively, and rates of 100%, 75%, 56%, and 42% for GOG groups of minimal, low, intermediate, and high risk. Subdivision of patients with FIGO Stage III disease based on tumor diameter and the number of involved lymph nodes appeared to be of prognostic value with a survival rate of 67% when tumor diameter was below 8 cm and less than three lymph nodes were involved but only 50% when either value was above the cut-off point. This study suggests that DNA ploidy status is not a prognostic value in vulvar squamous carcinoma, but the results support the value of utilizing the number of involved lymph nodes for prognosis assessment. The latter feature in combination with tumor size may be useful in the subdivision of FIGO Stage III patients into prognostic subgroups. PMID- 8346187 TI - Reactive states in lymph nodes resembling lymphomas or progressing to lymphomas: a selective review. PMID- 8346188 TI - Correspondence re: W. Lawrence Selby, Keith V. Nance, and H. Kim Park, CEA immunoreactivity in metastatic malignant melanoma. Mod. Pathol 5:415, 1992. PMID- 8346189 TI - Fluoride inhibition of yeast enolase: crystal structure of the enolase-Mg(2+)-F( )-Pi complex at 2.6 A resolution. AB - Enolase in the presence of its physiological cofactor Mg2+ is inhibited by fluoride and phosphate ions in a strongly cooperative manner (Nowak, T, Maurer, P. Biochemistry 20:6901, 1981). The structure of the quaternary complex yeast enolase-Mg(2+)-F(-)-Pi has been determined by X-ray diffraction and refined to an R = 16.9% for those data with F/sigma (F) > or = 3 to 2.6 A resolution with a good geometry of the model. The movable loops of Pro-35-Ala-45, Val-153-Phe-169, and Asp-255-Asn-266 are in the closed conformation found previously in the precatalytic substrate-enzyme complex. Calculations of molecular electrostatic potential show that this conformation stabilizes binding of negatively charged ligands at the Mg2+ ion more strongly than the open conformation observed in the native enolase. This closed conformation is complementary to the transition state, which also has a negatively charged ion, hydroxide, at Mg2+. The synergism of inhibition by F- and Pi most probably is due to the requirement of Pi for the closed conformation. It is possible that other Mg(2+)-dependent enzymes that have OH- ions bound to the metal ion in the transition state also will be inhibited by fluoride ions. PMID- 8346190 TI - Absolute and relative binding free energy calculations of the interaction of biotin and its analogs with streptavidin using molecular dynamics/free energy perturbation approaches. AB - We present calculations of the absolute and relative binding free energies of complexation of streptavidin with biotin and its analogs by means of a thermodynamic free energy perturbation method implemented with molecular dynamics. Using the recently solved crystal structure of the streptavidin-biotin complex, biotin was mutated into a dummy molecule as well as thiobiotin and iminobiotin both in the protein and in solution. The calculated absolute binding free energy was dependent on the simulation model used. Encouragingly, the "best models" provided a reasonable semiquantitative reproduction (-20 to -22 kcal/mol) of the experimental free energy (-18.3 kcal/mol). Furthermore, the calculated results give clear insights into the binding nature of the protein-ligand complex, showing that the van der Waals energy dominates the electrostatic and hydrogen bonding energies in the binding of biotin by streptavidin. Specifically, the mutation of biotin into a dummy molecule in solution has a delta G (van der Waals) approximately -4 kcal/mol, due to the cancellation of dispersion and repulsion "cavity" effects. On the other hand, in the protein, a very small free energy price must be paid to create a cavity since one already exists and the mutation of biotin into a dummy molecule has a delta G (van der Waals) approximately 15 kcal/mol. These results are also consistent with the interpretation that the entropy increase to be expected from hydrophobic interactions from desolvation of biotin is counterbalanced by a decrease in entropy accompanying the formation of buried hydrogen bonds, which have been derived from the apparently conflicting experimental data. They provide an alternative interpretation of the reason for the extremely high affinity of the biotin-streptavidin interaction than that recently proposed by Weber et al. (J. Am. Chem. Soc. 114:3197, 1992). In the case of the relative binding free energies, the calculated values of 3.8 +/- 0.6 and 7.2 +/- 0.6 kcal/mol compare well with the experimental values of 3.6 and 6.2 kcal/mol for the perturbation of biotin to thiobiotin and iminobiotin, respectively in the related protein avidin. The calculations indicate that desolvation of the ligand is important in understanding the relative affinity of the ligands with the protein. The above successful simulations suggest that the molecular dynamics/free energy perturbation method is useful for understanding the energetic features affecting the binding between proteins and ligands, since it is generally difficult to determine these factors unambiguously by experiment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8346191 TI - Principles and pitfalls in designing site-directed peptide ligands. AB - An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallographically refined structures of 14 peptide-protein complexes at 2.7 A resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change in conformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program an end-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligands were diffused into preexisting crystals. In such a large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints. PMID- 8346192 TI - A molecular dynamics study of solvent behavior around a protein. AB - The solvent structure and behavior around a protein were examined by analyzing a trajectory of molecular dynamics simulation of the trp-holorepressor in a periodic box of water. The calculated self diffusion coefficient indicated that the solvent within 10 A of the protein had lower mobility. Examination of the solvent diffusion around different atoms of different kinds of residues showed no general tendency. This fact suggested that the solvent mobility is not influenced significantly by the kind of the atom or residue they solvated. Distribution analysis around the protein revealed two peaks of water oxygen: a sharp one at 2.8 A around polar and charged atoms and a broad one at approximately 3.4 A around apolar atoms. The former was stabilized by water-protein hydrogen bonds, and the latter was stabilized by water-water hydrogen bonds, suggesting the existence of a hydrophobic shell. An analysis of protein atom-water radial distribution functions confirmed these shell structures around polar or charged atoms and apolar ones. PMID- 8346193 TI - The structure of a centrosymmetric protein crystal. AB - Crystals of racemic rubredoxin, prepared by independent chemical synthesis of the two enantiomers, have been grown and characterized. The unit cell contains two molecules, one of each enantiomer. Examination of the intensity distribution in the diffraction pattern revealed that the crystals are centrosymmetric. This was confirmed by solution of the structure to 2 A resolution via molecular replacement methods. The electron density maps are of very high quality due to the fact that the phase of each reflection must be exactly 0 degrees or exactly 180 degrees. These results demonstrate the feasibility of using synthetic racemic proteins to yield centrosymmetric protein crystals with electron density maps that have very low phase error and model bias. PMID- 8346194 TI - A comparison of the immunogenicity of a pair of enantiomeric proteins. AB - The immunogenicity of a folded, all D-amino acid protein, rubredoxin, has been compared with that for the corresponding L-protein enantiomer. Following multiple administrations with alum adjuvant, the L-protein induced a strong, specific IgG antibody response, whereas the D-protein did not. This relative lack of responsiveness to the D-protein cannot be attributed to rapid excretion, since it is retained at least 4 times longer than the natural L-protein. These observations provide the first direct evidence that a folded D-amino acid protein has low immunogenicity and is long lived in vivo. Proteins with such properties may be useful as molecular platforms in a variety of chemical and pharmacological applications. PMID- 8346195 TI - Are there ecological limits to population? AB - Policy on population and environment in the United States and abroad has been vacillating, unsure of its course; it would be more decisive if the several disciplines could agree on the nature of the problems and their urgency. The two disciplines principally concerned are biology and economics, and the contribution of this paper is to identify eight of the many axes or directions on which the methods and traditions of the two are different. For example, the first of the axes runs between contingency and orderly progress, with biology tending to seek out the former and economics the latter; thus biologists can more easily comprehend catastrophes, such as the demise of the dinosaurs or widespread desertification. The third axis concerns indefinite market-driven substitutability, seen by economists as resulting from scientific discovery; natural scientists, including biologists, whose discoveries make possible the substitutions, are skeptical. Axis 7 results from the fact that economics concentrates on goods that are on the market, and so deals with a truncated part of the commodity cycle, while ecology aims at the whole; because goods disappear from economic statistics once they pass into the hands of consumers many of their ecological effects are invisible. I believe that from similar further study of the two disciplines a common set of policy recommendations will ultimately emerge. PMID- 8346196 TI - E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product. AB - Previous studies have shown that the carboxyl-terminal region of E2F-1 (residues 368-437) can support transcriptional activation when linked to the DNA-binding domain of the yeast transcription factor GAL4. This region also contains an 18 residue retinoblastoma (RB)-binding sequence, raising the possibility that RB binding might inhibit the ability of E2F-1 to form protein-protein contacts required for activation. Here we report a further analysis of the E2F-1 activation domain. In addition, we show that overexpression of RB, but not the RB mutant, RBd22, can inhibit GAL4/E2F-1 activity in vivo. Moreover, expression of the simian virus 40 large tumor antigen (T antigen), but not the RB-binding defective T antigen point mutant, K1, can overcome this repression. Three different GAL4/E2F-1 mutants that activate transcription, but fail to bind to RB, are not significantly affected by overexpression of RB. These findings support a model wherein RB suppresses E2F-1-mediated transcriptional activation through direct physical association. PMID- 8346197 TI - Dominant lethality by expression of a catalytically inactive class I tRNA synthetase. AB - Alignment-guided mutagenesis was used to create an inactive, but toxic, aminoacyl tRNA synthetase. An Asp-96-->Ala (D96A) replacement in the nucleotide binding fold of the class I Escherichia coli isoleucyl-tRNA synthetase inactivates the enzyme without disrupting its competence for binding isoleucine tRNA. Expression of plasmid-encoded mutant enzyme in a cell with a wild-type ileS chromosomal allele resulted in cell death. Introduction of a second K732T substitution previously shown to weaken tRNA binding gives an inactive D96A/K732T double mutant. Expression of the double mutant is not lethal to E. coli. D96A but not the double mutant significantly inhibited in vitro charging of isoleucine tRNA by the wild-type enzyme. The results suggest a dominant tRNA binding-dependent arrest of cell growth caused by a reduction in the pool of a specific tRNA. Specific tRNA binding drugs may have therapeutic applications for treatment of microbial pathogens. PMID- 8346198 TI - Folding pathway mediated by an intramolecular chaperone. AB - The N-terminal propeptide of subtilisin, a serine protease, functions as an intramolecular chaperone which is crucial for proper folding of the active enzyme. This nascent N-terminal propeptide is removed after completion of the folding process. Here we present a possible pathway by which intramolecular chaperones mediate protein folding. Using circular dichroism to analyze acid denatured subtilisin we have identified a folding-competent state which can refold to an active conformation in the absence of the propeptide. Earlier work had shown that guanidine hydrochloride-denatured subtilisin was in a state incapable of folding in absence of its propeptide. Comparison of the folding incompetent and folding-competent states indicates that refolding is facilitated by the presence of residual structure present only in the folding-competent state. The analysis further indicates that the propeptide is essential for inducing this state. Therefore the folding-competent state may lie on--or be in rapid equilibrium with an intermediate on--the folding pathway of subtilisin. In the absence of the propeptide, formation of such a state--and hence refolding--is extremely slow. PMID- 8346199 TI - Properties and purification of an active biotinylated lactose permease from Escherichia coli. AB - A simplified approach for purification of functional lactose permease from Escherichia coli is described that is based on the construction of chimeras between the permease and a 100-amino acid residue polypeptide containing the biotin acceptor domain from the oxaloacetate decarboxylase of Klebsiella pneumoniae [Cronan, J. E., Jr. (1990) J. Biol. Chem. 265, 10327-10333]. Chimeras were constructed with a factor Xa protease site and the biotin acceptor domain in the middle cytoplasmic loop (loop 6) or at the C terminus of the permease. Each construct catalyzes active lactose transport in cells and right-side-out membrane vesicles. Moreover, the constructs are biotinylated in vivo, and in both chimeras, the factor Xa protease site is accessible from the cytoplasmic surface of the membrane. Both biotinylated permeases bind selectively to immobilized monomeric avidin and are eluted with free biotin in a high state of purity, and the loop 6 chimera catalyzes active transport after reconstitution into proteoliposomes. The methodology described should be applicable to other membrane proteins. PMID- 8346200 TI - Interferon alpha induces protein kinase C-epsilon (PKC-epsilon) gene expression and a 4.7-kb PKC-epsilon-related transcript. AB - Protein kinases play key roles in the induction by human interferon alpha (IFN alpha) of specific gene expression and biological activity in various human cell lines. We now report that IFN-alpha increased the 7-kb transcript for the epsilon isotype of protein kinase C (PKC-epsilon) and the cellular content of PKC-epsilon 24 and 48 hr after IFN-alpha addition (a 2-fold and 6-fold increase, respectively). Furthermore, IFN-alpha markedly induced a 4.7-kb transcript that hybridized to a PKC-epsilon-specific, but not to a PKC-eta-specific, cDNA probe. The induction of the 4.7-kb PKC-epsilon-related mRNA by IFN-alpha had the following properties reported for the classical IFN-alpha-stimulated genes: rapid kinetics of induction, high maintained levels in IFN-alpha-sensitive but not in IFN-alpha-resistant cell lines, protein synthesis-independent induction, and high sensitivity to inhibitors of protein tyrosine kinase activity. These results show that the regulation of gene expression by IFN-alpha include not only the classical IFN-alpha-stimulated genes but also the coordinated regulation of two PKC-epsilon-related transcripts that appeared to be highly relevant to the biological actions of IFN-alpha. PMID- 8346201 TI - Alloantibodies can discriminate class I major histocompatibility complex molecules associated with various endogenous peptides. AB - Molecules encoded by a single major histocompatibility complex class I gene can associate with any one of a large number of peptide ligands. T-cell receptors have the capacity to discriminate among these peptide-class I complexes and in many cases bind only a single peptide-class I complex with sufficient affinity to trigger effector function. In contrast, it is generally assumed that class I specific alloantibodies are indifferent to peptide heterogeneity, being directed toward allele-specific determinants on the molecule. In this report, three monoclonal antibodies were used to precipitate Kb molecules from cell lysates. Surprisingly, in each case a different set of peptides was found to be associated with Kb as detected by peptide-dependent Kb-specific alloreactive cytolytic T lymphocytes or by biochemical resolution. These results demonstrate that the affinity of binding by alloantibodies can be affected by the endogenous peptide ligand. PMID- 8346202 TI - Ethanol selectively blocks a noninactivating K+ current expressed in Xenopus oocytes. AB - There is presently a debate regarding the relative merits of lipid-based and protein-based theories of anesthesia and the action of ethanol in the central nervous system. Voltage-sensitive K+ channels play a key role as regulators of neuronal electrical activity and are potential targets of ethanol and other anesthetic agents. We investigated the action of low concentrations of ethanol on four structurally homologous cloned K+ channels expressed in Xenopus oocytes. We report that only the Drosophila Shaw2 channel, which does not inactivate upon prolonged depolarization, is rapidly and reversibly blocked by ethanol in a concentration-dependent manner (17-170 mM). The concentration dependence of the blockade can be explained by assuming a bimolecular interaction between ethanol and the channel. We also found that Shaw2 K+ channels were selectively blocked by halothane (1 mM). Our results support the "protein hypothesis" of ethanol and anesthetic action. These findings open ways to elucidate directly the molecular mechanism of interaction between general anesthetics and a voltage-sensitive K+ channel. PMID- 8346204 TI - Composite, large spirochetes from microbial mats: spirochete structure review. AB - Phenomena previously unknown in free-living spirochetes are reported: large-sized cells with variable diameter (length to 100 microns, width between 0.4 and 3.0 microns), composite structure (smaller spirochetes inside larger ones), and positive phototropic behavior. These bacteria, Spirosymplokos, are compared with all other spirochete genera. The large spirochete, grown in mixed culture, was studied live and by transmission EM. The protoplasmic cylinder was replete with spherical granules 20-32 nm in diameter, and three to six periplasmic 26-nm flagella were inserted subterminally. Comparably granulated and flagellated small spirochetes were located inside the protoplasmic cylinder and in the periplasm of the large ones. When exposed to air, movement became erratic, protoplasmic cylinders retracted to lie folded inside the outer membrane, and refractile membranous structures formed. From one to four structures per still-moving spirochete were seen. Spirosymplokos was enriched from laboratory samples exposed to oxygen-rich and desiccating, but not dry, conditions for at least 4 mo after removal of microbial mat from the field. PMID- 8346203 TI - hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus. AB - The six-cysteine P-domain motif forms the basic repeat unit of a growing family of mucin-associated peptides. A precursor for a human secretory polypeptide has been discovered by molecular cloning and deduced to have a single P-domain, termed hP1.B. The pre-pro-peptide has 67% amino acid identity with rat intestinal trefoil factor. We find, using the techniques of RNA analysis and in situ hybridization, that this P-domain peptide is expressed in the human gastrointestinal tract, where a number of pathological conditions affect its expression, and surprisingly find it is expressed in the uterus also. In the intestine, hP1.B is expressed by goblet cells, but in Crohn disease this peptide is synthesized and secreted additionally by the ulcer-associated cell lineage that is known to secrete two other trefoil peptides, pS2 and spasmolytic polypeptide (hSP). In the stomach, hP1.B mRNA is relatively scarce but is more abundant in foci of intestinal metaplasia and near to ulceration. Mucin-rich epithelial cells in hyperplastic polyps of the colon also express this peptide. The discovery of this P-domain peptide and its expression in association with mucins support the hypothesis that P-domains with mucins may subserve related functions in the maintenance and repair of mucosal function. PMID- 8346206 TI - Calsequestrinlike calcium-binding protein is expressed in calcium-accumulating cells of Pistia stratiotes. AB - To contend with high calcium (Ca) levels in the environment, many plant species contain crystal idioblasts, specialized cells which accumulate large amounts of Ca as oxalate crystals. The biochemical processes involved in the accumulation of Ca in crystal idioblasts are unknown, as these cells constitute only a minor proportion of the total plant tissue. To address how crystal idioblasts buffer cytosolic Ca during crystal formation, we purified these cells from water lettuce and assessed their biochemistry. We show here that crystal idioblast cells contain three Ca-binding proteins not detectable in mesophyll cells. One of the Ca-binding proteins shares antigenicity with rabbit calsequestrin, a high capacity low-affinity Ca-binding protein, and is encoded by related nucleotide sequences. Immunocytochemical localization studies further demonstrate that a calsequestrinlike protein is present primarily in crystal idioblasts and is preferentially localized in the endoplasmic reticulum, an organelle enriched in Ca as evidenced by vital staining. We thus conclude that crystal idioblasts possess a buffering system involving calsequestrinlike proteins, a process that likely plays an essential role in the bulk control of Ca in plant cells. PMID- 8346205 TI - Chlamydomonas mutants affected in the light-dependent step of sexual differentiation. AB - Sexual differentiation of Chlamydomonas reinhardtii is induced by the consecutive action of two extrinsic cues--nitrogen deprivation and blue light. The definition of a blue light-dependent step in gamete formation provided a basis for the isolation of mutants altered in the signal transduction pathway by which light controls sexual differentiation. In one mutant (lrg1), gamete formation has become light independent. In the other mutant (lrg2), perception or transduction of the light signal appears to be partially impaired. In both mutants, the expression of genes activated by light in the late phase of gamete formation is affected. Genetic analyses showed that genes LRG1 and LRG2 are linked. The recessive nature of the lrg1-1 mutation implies that the gene encodes a negative factor or a protein that controls the activity of a negative factor. In the case of lrg2-1, neither wild-type nor mutant allele was dominant. Rather, two copies of the lrg2-1 gene simulate a wild-type phenotype. The identification of genetic loci in the pathway for blue light-mediated differentiation provides a basis for the isolation of signal transduction genes in Chlamydomonas. PMID- 8346207 TI - Hammerhead ribozymes: importance of stem-loop II for activity. AB - The activity of several hammerhead ribozyme constructs with constant lengths of stems I and III of 5 nt each but with variously shortened stems II is reported. Stems with 2 bp rather than the conventional 4 bp show essentially unaltered catalytic activity, independent of the composition of the tetraloop. Further reduction in size to 1 bp or 0 bp decreases activity drastically. Inversion of the G10.1.C11.1 bp next to the invariant core leads to a loss in activity, even when the stem consists of 4 bp. Thus, the minimal structural requirement for stem loop II is a 2-bp stem with a conserved G.C bp. The reduction in catalytic activity is predominantly a result of a decrease of catalytic constant kcat, whereas Km is only slightly affected. Thus, the structural requirement for optimal activity in these constructs where the chemical-cleavage step is rate limiting is determined by the stabilization of the transition state. PMID- 8346208 TI - Determination of the phylogenetic relationships among Pacific salmonids by using short interspersed elements (SINEs) as temporal landmarks of evolution. AB - Several subfamilies of the salmonid Hpa I short interspersed element (SINE) family were isolated from salmonid genomes and were sequenced. For each genomic locus that represented the subfamily, amplification by PCR of the orthologous loci in the 12 fish allowed us to determine the order of branching of the Pacific salmonid species. The deduced phylogeny suggests three evolutionary lines, namely, a line of chum salmon, pink salmon, and kokanee; a line of coho salmon and chinook salmon; and a line of steelhead trout. Our data also support a change in the phylogenetic assignment of steelhead trout from Salmo to Oncorhynchus. We present here an extensive phylogenetic tree constructed from an analysis of differential insertion of SINEs, and we propose that SINE insertion analysis is one of the best available methods for clarifying the order of divergence of closely related species. PMID- 8346209 TI - The cAMP-response-element-binding protein interacts, but Fos protein does not interact, with the proenkephalin enhancer in rat striatum. AB - The proenkephalin gene is a well-studied model of transcription factor-target gene interaction in the nervous system and has been proposed as a regulatory target of the protein product of the immediate-early gene c-fos. This regulatory mechanism has been proposed, in part, because the cAMP response element 2 (CRE-2) site, the key DNA regulatory element within the proenkephalin second-messenger inducible enhancer, avidly binds AP-1 proteins, including Fos, in vitro. However, we observe a dissociation in the time course of activation of c-fos and proenkephalin mRNA in rat striatum after administration of the dopamine D2 receptor antagonist haloperidol. This result prompted us to investigate the composition of protein complexes in striatal nuclear extracts that bind to the CRE-2 site. Even though our striatal nuclear extracts had substantial basal and haloperidol-inducible AP-1-binding activities that contained Fos, we could not detect Fos in complexes bound to the CRE-2 element. Instead, as determined by antibody supershift analysis, we detect CRE-binding protein (CREB)-like proteins binding to CRE-2 in both basal and haloperidol-stimulated conditions. Finally, we show that haloperidol induces CREB protein phosphorylation in striatum. PMID- 8346210 TI - Genetic fusion of subunits of a dimeric protein substantially enhances its stability and rate of folding. AB - The gene V protein of bacteriophage f1 is a single-stranded DNA and RNA-binding protein composed of two identical subunits. We have constructed single-chain variants of the protein using short peptide linkers of five or six amino acids to connect the carboxyl terminus of one monomer to the amino terminus of the second monomer. The resulting subunit-fusion gene V proteins were found to bind single stranded DNA nearly as tightly as the wild-type protein. Denaturation measurements show that the subunit-fusion gene V proteins are 5 kcal/mol (1 kcal = 4.18 kJ) more stable than the wild-type protein at a protein concentration of 10 microM. The rate of unfolding of the protein is essentially unaffected by the fusion of monomeric subunits, whereas the rate of folding is greatly enhanced. Our results suggest a simple way of obtaining a substantial thermodynamic stabilization for some oligomeric proteins. PMID- 8346212 TI - Regression of established macroscopic liver metastases after in situ transduction of a suicide gene. AB - The herpes simplex virus type 1 thymidine kinase (HSV1-TK) converts nontoxic nucleoside analogs such as ganciclovir into phosphorylated compounds that act as chain terminators and specifically kill dividing cells. This property could be exploited for the treatment of tumors that are made up of rapidly dividing cells invading a nonproliferating tissue. For this purpose, specific expression of the suicide gene into dividing tumor cells can be further targeted by using retroviral-mediated gene transfer. We investigated whether the direct intratumoral transduction of a suicide gene might induce the elimination of malignant solid tumors. Rats with established macroscopic liver metastases were given an intratumoral injection of packaging cells producing either HSV1-TK- or lacZ-expressing recombinant retroviral particles. All rats were next treated with ganciclovir. A dramatic regression of the tumor volume was observed in the HSV1 TK-treated animals. The residual tumors were mostly made up of a massive fibrotic reaction, with the mean cancer cell mass being reduced approximately 60-fold compared to controls. In some animals, the residual tumors were devoid of cancer cells. This treatment efficacy appears in part due to a "bystander effect" in which phosphorylated ganciclovir could be transferred from cell to cell and to an active local immune reaction evidenced by massive infiltration of the tumors by macrophages and both CD4+ and CD8+ lymphocytes. This efficient therapeutic approach might be an ultimate treatment for disseminated liver metastases in humans and could also be applied to treatment of a large variety of solid tumors. PMID- 8346211 TI - Regional cerebral glucose metabolism in late-life depression and Alzheimer disease: a preliminary positron emission tomography study. AB - Eight subjects with late-life depression, eight subjects with probable Alzheimer disease, and eight healthy age-matched controls were studied using 2-[18F]fluoro 2-deoxy-D-glucose positron emission tomography in the resting state with their eyes open and ears unoccluded. The depressed subjects showed widespread reductions in the regional cerebral metabolic rate for glucose in most major neocortical, subcortical, and paralimbic regions that were significantly different from control values (P < 0.01). The metabolic decrements in the depressed group were comparable in magnitude to those seen in the Alzheimer disease group. These data demonstrate widespread nonfocal decline in glucose metabolism in late-life depression that is comparable to the hypometabolism seen in Alzheimer disease. These findings have pathophysiological implications in major depressive disorder in the elderly. PMID- 8346213 TI - Stabilization and ribosome association of unspliced pre-mRNAs in a yeast upf1- mutant. AB - Nonsense-mediated mRNA decay, the accelerated turnover of mRNAs transcribed from genes containing early nonsense mutations, is dependent on the product of the UPF1 gene in yeast. Mutations that inactivate UPF1 lead to the selective stabilization of mRNAs containing early nonsense mutations but have no effect on the half-lives of almost all other mRNAs. Since the transcripts of nonsense alleles are not typical cellular constituents, we sought to identify those RNAs that comprise normal substrates of the nonsense-mediated mRNA decay pathway. Many yeast pre-mRNAs contain early in-frame nonsense codons and we consider it possible that a role of this pathway is to accelerate the degradation of pre mRNAs present in the cytoplasm. Consistent with this hypothesis, we find that, in a strain lacking UPF1 function, the CYH2, RP51B, and MER2 pre-mRNAs are stabilized 2- to 5-fold and are associated with ribosomes. We conclude that a major source of early nonsense codon-containing cytoplasmic transcripts in yeast is pre-mRNAs and that the UPF1 protein may be part of a cellular system that ensures that potentially deleterious nonsense fragments of polypeptides do not accumulate. PMID- 8346214 TI - Expression of transduced tropomyosin 1 cDNA suppresses neoplastic growth of cells transformed by the ras oncogene. AB - Synthesis of certain members of the tropomyosin family of microfilament associated proteins is suppressed in fibroblasts neoplastically transformed by a number of retroviral oncogenes, by transforming growth factor alpha, and by chemical mutagens. To test whether tropomyosin suppression is a required event in neoplastic transformation, expression of one of two suppressed tropomyosins in NIH 3T3 mouse cells transformed by the ras oncogene was restored by retrovirally mediated cDNA transfer. Cells expressing the inserted cDNA showed partial restoration of microfilament bundle formation (which is typically deranged in transformed cells) together with increased cytoplasmic spreading. More importantly, they lost anchorage-independent growth capability, and the onset of tumor growth in athymic mice was delayed. When tumors arose they no longer expressed the inserted cDNA. These observations support the conclusion that tropomyosin suppression is a necessary event for the expression of components of the transformed phenotype, particularly with respect to anchorage-independent growth and tumorigenesis, which correlate closely with neoplastic potential. This potentially reversible requirement may link different initial events produced by a variety of oncogenic modalities to a common pathway leading to neoplastic growth. PMID- 8346215 TI - Identification of four murine cDNAs encoding putative protein kinases from primitive embryonic stem cells differentiated in vitro. AB - Protein kinases transduce signals from extracellular ligands in the hematopoietic and other systems through direct phosphorylation of tyrosine, serine, or threonine residues. Little is known about the ligands and receptors that are important in the earliest stages of development--i.e., stem cell self-renewal and lineage commitment. We have made use of the lineage differentiation potential of the murine embryonic stem cell system to clone partial cDNAs encoding four putative protein kinases. Three of the four genes contain the highly conserved residues Asp-Phe-Gly in domain VII of the protein kinase family. These genes are candidates for receptors or downstream effectors of cytokines that regulate self renewal and lineage commitment in embryogenesis. PMID- 8346216 TI - Duplication of the CD8 beta-chain gene as a marker of the man-gorilla-chimpanzee clade. AB - In earlier studies we have found that the gene encoding the CD8 beta chain is duplicated in man. We demonstrate here that the duplicated genes are both located on chromosome 2. We have also studied the moment of the duplication event relative to the evolution of higher primates by using genomic DNA of a panel of primates. Our data strongly suggest that duplication occurred after the orangutan lineage had split and before the chimpanzee, gorilla, and man clade diverged, some 8-9.5 million years ago. This result makes the CD8 beta-chain gene duplication a convenient marker for the study of the evolution of higher primates. PMID- 8346217 TI - Interleukin 1 induction of the c-jun promoter. AB - Interleukin 1 (IL-1) induces pleiotropic effects in many cell types during inflammation and immunity. We have recently shown how the IL-1 signal is transmitted to the nucleus: In T cells and in pituitary cells, IL-1 induced genes via activation of the nuclear factor AP-1. We now demonstrate how IL-1 activates the AP-1 factor in liver cells, which are a major target for IL-1 during the acute phase response in vivo. IL-1 induced gene transcription of both AP-1 components, c-jun and c-fos. IL-1 also increased the stability of c-jun mRNA. We define two enhancer sites in the jun promoter that are required for induction by IL-1. Although the binding sites share some similarity with the AP-1 binding site, the nuclear factors binding the jun motifs are not composed of Jun or Fos proteins. Thus these data identify two binding proteins that serve as one of the first nuclear targets for IL-1 signal transduction. PMID- 8346218 TI - Reproductive failure of dominant males in the poeciliid fish Limia perugiae determined by DNA fingerprinting. AB - Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behavior and access to the females. In general, social dominance requires large investments, which in turn then may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups (one or two males with one or two females) due to the difficulties of determining paternity by conventional methods. DNA fingerprinting overcomes these problems by offering the possibility to determine genetic relationships and mating patterns within larger groups [Burke, T. (1989) Trends Ecol. Evol. 4, 139-144]. We show here that in the poeciliid fish Limia perugiae, in small mating groups the dominant male has a mating success of 100%, whereas in larger groups its contribution to the offspring unexpectedly drops to zero. PMID- 8346220 TI - Habitat-dependent hybrid parentage and differential introgression between neighboringly sympatric Daphnia species. AB - Allozyme, morphological, and PCR-generated mtDNA markers were used to analyze hybrid parentage and introgression between the neighboringly sympatric crustaceans Daphnia galeata mendotae and Daphnia rosea. mtDNA analysis of D. galeata mendotae from 15 lakes and of D. rosea from 8 lakes revealed species specific fragment patterns resulting from TaqI and RsaI digestion. No individuals of one parent species possessed the typical mtDNA of the other parent species, suggesting that mtDNA introgression is rare or nonexistent. Hybrids from 18 lakes possessed either the mtDNA patterns of D. rosea or of D. galeata mendotae, indicating that reciprocal hybridization occurs. The mtDNA genome of the dominant parent species in a lake was overrepresented in the hybrids, suggesting that hybridization most often involves females of the common species and males of the rare species. Such a pattern is consistent with the differing importance of density to the environmental induction of males and sexual eggs in Daphnia. For the assessment of nuclear gene flow, eight sympatric populations of each parental taxon and seven allopatric populations of D. galeata were analyzed for allozyme variation at nine polymorphic loci. Our results provided evidence for asymmetric interspecific gene flow involving alleles at six loci that are unlikely to be convergent or symplesiomorphic. This reticulate evolution accounted for much of the genetic divergence between European and North American populations of D. galeata. PMID- 8346219 TI - Molecular cloning of the human kidney differentiation antigen gp160: human aminopeptidase A. AB - gp160 is a cell surface differentiation-related glycoprotein of 160 kDa expressed by epithelial cells of the glomerulus and proximal tubule cells of the human nephron but only by a subset of renal cell carcinomas (RCCs). We have reported that gp160 expression correlates with the resistance of cultured RCCs to the antiproliferative effects of alpha interferon, while lack of expression correlates with sensitivity to alpha interferon. In this study, we have purified gp160 protein, obtained partial sequences of random peptides, and isolated a full length cDNA. The gp160 cDNA possesses 78% homology to the murine BP-1/6C3 antigen, a B-lymphocyte differentiation protein that exhibits aminopeptidase A (APA; EC 3.4.11.7) activity. Enzymatic assays on human RCC cell lines indicated a 100% concordance between APA activity and gp160 expression. APA activity of gp160 expressing RCC cells was increased or decreased by a panel of APA activators or inhibitors, respectively. Furthermore, anti-gp160 monoclonal antibodies immunoprecipitate APA activity from RCC cell lysates and selectively deplete APA activity from RCC cell extracts. These data indicate that the gp160 human kidney/RCC glycoprotein is human APA. PMID- 8346221 TI - Broad-spectrum virus resistance in transgenic plants expressing pokeweed antiviral protein. AB - Exogenous application of pokeweed antiviral protein (PAP), a ribosome-inhibiting protein found in the cell walls of Phytolacca americana (pokeweed), protects heterologous plants from viral infection. A cDNA clone for PAP was isolated and introduced into tobacco and potato plants by transformation with Agrobacterium tumefaciens. Transgenic plants that expressed either PAP or a double mutant derivative of PAP showed resistance to infection by different viruses. Resistance was effective against both mechanical and aphid transmission. Analysis of the vacuum infiltrate of leaves expressing PAP showed that it is enriched in the intercellular fluid. Analysis of resistance in transgenic plants suggests that PAP confers viral resistance by inhibiting an early event in infection. Previous methods for creating virus-resistant plants have been specific for a particular virus or closely related viruses. To protect plants against more than one virus, multiple genes must be introduced and expressed in a single transgenic line. Expression of PAP in transgenic plants offers the possibility of developing resistance to a broad spectrum of plant viruses by expression of a single gene. PMID- 8346222 TI - Corticotropin-releasing factor mRNA in rat thymus and spleen. AB - Corticotropin-releasing factor (CRF) initiates stress-induced immunosuppression via the hypothalamic-pituitary-adrenal axis. CRF has also been shown to have direct stimulatory and suppressive effects on immune cells. We have previously detected immunoreactive and bioactive CRF in the rat spleen and thymus. To determine if CRF is synthesized in these tissues, we analyzed rat spleen and thymus for the presence of CRF mRNA. RNA was reverse transcribed, and the resulting cDNA was amplified by the polymerase chain reaction with CRF gene specific oligonucleotide primers. After Southern blotting and hybridization with an internal CRF gene probe, a product of the expected size was detected in the spleen, thymus, and hypothalamus (positive control) but not in liver or kidney (negative controls), indicating that CRF is synthesized in the spleen and thymus. Furthermore, CRF could be secreted from splenic and thymic adherent cells in culture. Secretion increased severalfold in response to nordihydroguaiaretic acid (NDGA), a lipoxygenase pathway inhibitor, whereas interleukin 1 had no effect, suggesting that regulation of CRF secretion may differ from that in the hypothalamus. CRF mRNA was detected in NDGA-stimulated thymic adherent cells and in both control and NDGA-stimulated splenic nonadherent cells. The finding that CRF is synthesized in the spleen and thymus suggests that locally synthesized "immune" CRF, acting as an autocrine or paracrine cytokine, may have direct regulatory effects on immune function. PMID- 8346223 TI - An erythromycin analog produced by reprogramming of polyketide synthesis. AB - The polyketide-derived macrolactone of the antibiotic erythromycin is made through successive condensation and processing of seven three-carbon units. The fourth cycle involves complete processing of the newly formed beta-keto group (beta-keto reduction, dehydration, and enoyl reduction) to yield the methylene that will appear at C-7 of the lactone ring. Synthesis of this molecule in Saccharopolyspora erythraea is determined by the three large eryA genes, organized in six modules, each governing one condensation cycle. Two amino acid substitutions were introduced in the putative NAD(P)H binding motif in the proposed enoyl reductase domain encoded by eryAII. The metabolite produced by the resulting strain was identified as delta 6,7-anhydroerythromycin C resulting from failure of enoyl reduction during the fourth cycle of synthesis of the macrolactone. This result demonstrates the involvement of at least the enoyl reductase from the fourth module in the fourth cycle and indicates that a virtually complete macrolide can be produced through reprogramming of polyketide synthesis. PMID- 8346224 TI - Single core polypeptide in the reaction center of the photosynthetic bacterium Heliobacillus mobilis: structural implications and relations to other photosystems. AB - The gene for a reaction center core polypeptide from the anoxygenic photosynthetic bacterium Heliobacillus mobilis was cloned and sequenced. The deduced amino acid sequence consists of 609 residues with a molecular mass of 68 kDa. An adjacent open reading frame is not transcribed under our experimental conditions. No evidence for a second related reaction center core gene was found. The primary sequence of the reaction center protein (P800 protein) shows a high percentage of sequence identity to photosystem I in a cysteine-containing loop, which is the putative binding site of the iron-sulfur center FX and in the preceding hydrophobic region. Our data imply a homodimeric organization of the reaction center. This is fundamentally different from photosystem I and most other photosynthetic reaction centers, where the reaction center core is composed of two similar but nonidentical subunits. PMID- 8346225 TI - Identification, cloning, and nucleotide sequencing of the ornithine decarboxylase antizyme gene of Escherichia coli. AB - The ornithine decarboxylase antizyme gene of Escherichia coli was identified by immunological screening of an E. coli genomic library. A 6.4-kilobase fragment containing the antizyme gene was subcloned and sequenced. The open reading frame encoding the antizyme was identified on the basis of its ability to direct the synthesis of immunoreactive antizyme. Antizyme shares significant homology with bacterial transcriptional activators of the two-component regulatory system family; these systems consist of a "sensor" kinase and a transcriptional regulator. The open reading frame next to antizyme is homologous to sensor kinases. Antizyme overproduction inhibits the activities of both ornithine and arginine decarboxylases without affecting their protein levels. Extracts from E. coli bearing an antizyme gene-containing plasmid exhibit increased antizyme activity. These data strongly suggest that (i) the cloned gene encodes the ornithine decarboxylase antizyme and (ii) antizyme is a bifunctional protein serving as both an inhibitor of polyamine biosynthesis as well as a transcriptional regulator of an as yet unknown set of genes. PMID- 8346226 TI - Early evolution of photosynthesis: clues from nitrogenase and chlorophyll iron proteins. AB - Chlorophyll (Chl) is often viewed as having preceded bacteriochlorophyll (BChl) as the primary photoreceptor pigment in early photosynthetic systems because synthesis of Chl requires one fewer enzymatic reduction than does synthesis of BChl. We have conducted statistical DNA sequence analyses of the two reductases involved in Chl and BChl synthesis, protochlorophyllide reductase and chlorin reductase. Both are three-subunit enzymes in which each subunit from one reductase shares significant amino acid identity with a subunit of the other, indicating that the two enzymes are derived from a common three-subunit ancestral reductase. The "chlorophyll iron protein" subunits, encoded by the bchL and bchX genes in the purple bacterium Rhodobacter capsulatus, also share amino acid sequence identity with the nitrogenase iron protein, encoded by nifH. When nitrogenase iron proteins are used as outgroups, the chlorophyll iron protein tree is rooted on the chlorine reductase lineage. This rooting suggests that the last common ancestor of all extant photosynthetic eubacteria contained BChl, not Chl, in its reaction center, and implies that Chl-containing reaction centers were a late invention unique to the cyanobacteria/chloroplast lineage. PMID- 8346227 TI - A base-pairing interaction between U2 and U6 small nuclear RNAs occurs in > 150S complexes in HeLa cell extracts: implications for the spliceosome assembly pathway. AB - In mammalian cells, base pairing between the U2 and U6 small nuclear RNAs is required during pre-RNA splicing. We show by psoralen crosslinking of HeLa nuclear extract that U2.U6 base pairing occurs within abundant ribonucleoprotein complexes that sediment at > 150 S in glycerol gradients. All of the spliceosomal RNAs (U1, U2, U4, U5, and U6) cosediment with these large complexes, suggesting that they may be related to small nuclear RNA-containing structures called speckles/coiled bodies or snurposomes, which have been visualized in mammalian or amphibian nuclei, respectively. In contrast to nuclear extract, S100 extract, which is splicing-defective and lacks the > 150S complexes, does not contain base paired U2.U6. However, U2.U6 base pairs form in S100 extract that has been made splicing-competent by supplementation with Ser/Arg-rich (SR) proteins, ATP, and an adenovirus splicing substrate. During splicing in supplemented S100 extract, U2.U6 base pairing precedes the appearance of splicing intermediates and occurs initially in an approximately 60S spliceosome complex but also in progressively larger (100-300 S) complexes. Possible functional relationships between the 60S spliceosome and the > 150S complexes are discussed. PMID- 8346228 TI - Molecular cloning and sequencing of a canine tracheobronchial mucin cDNA containing a cysteine-rich domain. AB - To date the complete sequence of only one mammalian mucin cDNA, MUC1, has been reported, although several mucin proteins have been partially characterized. Here we report the nucleotide sequence of a canine tracheal mucin cDNA containing two potential translation initiation codons, one translation termination codon and a poly(A) tail. A lambda gt11 cDNA library prepared from canine tracheal epithelial cells was screened with polyclonal anti-apo-canine tracheal mucin antibodies with the aim of obtaining the deduced amino acid sequence of the mucin core protein. Antibody-positive clones containing overlapping inserts of various lengths were purified and used for nucleotide sequencing. Based on the sequencing data, synthetic oligonucleotide primers were constructed and both ends (5' and 3') of the cDNA were determined. The complete sequence was 3.7 kb and included an open reading frame with coding capacity for 1118 aa, two translation initiation ATG codons in context with Kozak consensus sequences, one polyadenylylation site, and a poly(A) stretch. The protein was rich in Thr, Pro, Ser, Gly, and Ala and poor in Tyr, Phe, and Trp. Although tandem repeats of amino acids were absent in the deduced canine tracheal mucin sequence, motifs TPTPTP and TTTTPV appeared 13 and 19 times, respectively. The C-terminal region contained a Cys-rich domain (although a few Cys residues were also present in the middle of the protein) as has been reported for bovine submaxillary mucin, porcine submaxillary mucin, rat intestinal mucin, human intestinal mucin, and frog skin mucin. This suggested that a broad group of mucins contain such a Cys-rich domain whose functional significance is yet to be understood. Three potential N-glycosylation sites were present in canine tracheal mucin and the amino acid sequence showed homology with both human tracheal and intestinal mucins. The N-terminal domain showed more flexibility (probably due to a high number of Pro residues in this region) when analyzed by the University of Wisconsin Genetics Computer Group program package to determine the predicted secondary structure. Evaluation of the transcripts using the canine mucin cDNA as a probe indicated a polydisperse message with total RNA. PMID- 8346229 TI - The discriminator base influences tRNA structure at the end of the acceptor stem and possibly its interaction with proteins. AB - For many tRNAs, the discriminator base preceding the CCA sequence at the 3' end is important for aminoacylation. We show that the discriminator base influences the stability of the 1.72 base pair onto which it is stacked. Mutations of the discriminator base from adenosine to cytidine or uridine make the cytidine residue in the C1-G72 base pair of mutant Escherichia coli initiator tRNAs more reactive toward sodium bisulfite, the single-strand-specific reagent. The activity of the enzyme Met-tRNA transformylase toward these and other mutant initiator tRNAs is also consistent with destabilization of the 1.72 base pair in vitro and in vivo. By influencing the strength of the 1.72 base pair, the discriminator base could affect the energetic cost of opening the base pair and modulate the structure of the tRNA near the site of aminoacylation. For some aminoacyl-tRNA synthetases and other proteins that interact with tRNA, these factors could be important for specific recognition and/or formation of the transition state during catalysis. PMID- 8346230 TI - Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8. AB - The interaction of interleukin 8 (IL-8) with heparin was studied by using synthetic IL-8 analogs with C- and N-terminal truncations. Elimination of the N terminal region preceding the first cysteine, which constitutes the IL-8 receptor binding site, did not affect the affinity to heparin-Sepharose. Affinity, however, decreased with progressive truncation at the C terminus, and no binding was observed when the C-terminal alpha-helix was eliminated. The effect of heparin and other glycosaminoglycans on IL-8 activity was also tested. When IL-8 was applied together with heparan sulfate, neutrophil chemotaxis in vitro was enhanced up to 4-fold, and the stimulus-dependent increase in cytosolic free Ca2+ increased markedly in both rate and peak value. Heparin had a similar effect on the Ca2+ response but did not enhance chemotaxis. The glycosaminoglycans by themselves did not elicit neutrophil responses. Their enhancing effect was restricted to stimulation with IL-8 and was not observed when the unrelated chemoattractant fMet-Ile-Phe-Leu was used as the stimulus. Elastase released from stimulated neutrophils was inhibited by heparin, heparan sulfate, and, to a lesser extent, chondroitin sulfate B, confirming previous observations. Taken together, these results suggest that heparan sulfate, which is present on the endothelial cell surface and in the basement membrane, may have a dual function in diapedesis, promotion of IL-8-dependent transmigration of neutrophils, and protection of the tissue microenvironment from damage by lytic enzymes released from the migrating cells. PMID- 8346231 TI - Identification of an isoform of the estrogen receptor messenger RNA lacking exon four and present in the brain. AB - An isoform of the estrogen receptor messenger RNA (ER-mRNA) was identified in RNA from the brain of lizards and rats. Poly(A)+ RNA from brain and uteri was reverse transcribed using gene-specific primer for the ER. The resulting complementary DNA was amplified in a polymerase chain reaction followed by cloning and sequencing of the amplified products. This isoform lacks exon four and is designated delta 4 ER-mRNA. Although several isoforms of the ER have been described from cancerous cells, to our knowledge, none has been identified previously in the brain. Furthermore, the delta 4 isoform is the only isoform detected in normal tissue. The delta 4 isoform appeared most abundant in RNA from brain tissue, whereas uterine RNA contained only trace amounts of the isoform. Apparently, tissue-specific alternative splicing accounts for these differences in abundance. Because exon four encodes a part of the steroid-binding domain, we predict that the corresponding protein encoded by the isoform will not bind estradiol and may therefore belong to a growing subclass of the steroid/thyroid/vitamin superfamily known as orphan receptors. We predict that the putative delta 4 protein may function as a ligand-independent transcription factor that acts on the same DNA response elements as the conventional ER. The abundance of this isoform in the brain relative to the uterus raises fundamental questions regarding the regulation of estrogen-responsive genes in different tissues. PMID- 8346232 TI - Covariation of mutations in the V3 loop of human immunodeficiency virus type 1 envelope protein: an information theoretic analysis. AB - The V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein is a highly variable region that is both functionally and immunologically important. Using available amino acid sequences from the V3 region, we have used an information theoretic quantity called mutual information, a measure of covariation, to quantify dependence between mutations in the loop. Certain pairs of sites, including non-contiguous sites along the sequence, do not have independent mutations but display considerable, statistically significant, covarying mutations as measured by mutual information. For the pairs of sites with the highest mutual information, specific amino acids were identified that were highly predictive of amino acids in the linked site. The observed interdependence between variable sites may have implications for structural or functional relationships; separate experimental evidence indicates functional linkage between some of the pairs of sites with high mutual information. Further specific mutational studies of the V3 loop's role in determining viral phenotype are suggested by our analyses. Also, the implications of our results may be important to consider for V3 peptide vaccine design. The methods used here are generally applicable to the study of variable proteins. PMID- 8346233 TI - Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth. AB - Hepsin was previously identified as a putative cell-surface serine protease. When hepatoma cells were treated with anti-hepsin antibodies, their growth was substantially arrested, suggesting the requirement of hepsin molecules present at the cell surface for normal cell growth. This was further supported by a gross inhibition of cell growth with hepsin-specific antisense oligonucleotides. Upon treatment of cells with antisense oligonucleotides, rapid reduction in cellular hepsin was observed. This reduction in cellular hepsin levels was accompanied by drastic morphological changes. Various tissues in the developing mouse embryo showed greatly elevated hepsin levels in regions of active proliferation. These results indicate that hepsin plays an essential role in cell growth and maintenance of cell morphology. PMID- 8346234 TI - Inhibition of RNA polymerase II transcription by oligonucleotide-RecA protein filaments targeted to promoter sequences. AB - In the presence of RecA protein, which plays a major role in genetic recombination in Escherichia coli, an oligodeoxyribonucleotide can find its homologous counterpart in double-stranded DNA and form triple-stranded structures. A triple-stranded structure formed by an oligonucleotide with a sequence overlapping essential regulatory elements of a viral promoter, such as TATA or GC boxes, inhibited in vitro transcription driven by RNA polymerase II. An oligonucleotide with eight nucleotides homologous to its target suppressed RNA polymerase II activity in HeLa cell extracts. This procedure offers a potential alternative to the usual mutational analysis of transcriptional promoters. PMID- 8346235 TI - Engineering of stable and fast-folding sequences of model proteins. AB - The statistical mechanics of protein folding implies that the best-folding proteins are those that have the native conformation as a pronounced energy minimum. We show that this can be obtained by proper selection of protein sequences and suggest a simple practical way to find these sequences. The statistical mechanics of these proteins with optimized native structure is discussed. These concepts are tested with a simple lattice model of a protein with full enumeration of compact conformations. Selected sequences are shown to have a native state that is very stable and kinetically accessible. PMID- 8346236 TI - Isolation of x-ray-inducible transcripts from radioresistant human melanoma cells. AB - Twelve x-ray-induced transcripts (xips), differentially expressed 8- to 230-fold in x-irradiated versus unirradiated radioresistant human melanoma (U1-Mel) cells, were isolated as cDNA clones (xip1 through xip12) after four rounds of differential hybridization. Northern analyses revealed rare, medium, and abundant xips, ranging in size from 1.2 to 10 kb. All transcripts were transiently expressed and induced by low, but not by high (> 600 cGy), doses of radiation. Three transcripts (xip4, -7, and -12) were induced only by ionizing radiation, and many (i.e., xip1, -2, -3, -5, -6, -8, -9, -10, and -11) were also induced by UV irradiation or phorbol 12-myristate 13-acetate. Heat shock did not induce any of the xips, but it decreased basal levels of xip4, -7, -11, and -12. Three xip cDNA clones were identified as encoding thymidine kinase, DT diaphorase, and tissue-type plasminogen activator. The remaining nine cDNA clones showed little homology to known genes. Three clones contained regions homologous to c-fes/fps protooncogene, recombination activating gene 1, or the human angiogenesis factor gene. X-ray-inducible genes may function in damaged cells to regulate DNA repair, apoptosis, mutagenesis, and carcinogenesis. PMID- 8346237 TI - Integration of gene maps: chromosome 21. AB - Physical, cytogenetic, and genetic data including microsatellite markers and a covering sequence-tagged site (STS) map have been entered into a location database and integrated into a summary map that subsumes a composite physical location, sex-specific genetic locations, cytogenetic and regional assignments, mouse homology, rank, and references. With the omission of 52 loci whose location is known only from cytogenetic assignment to an interval greater than 10 megabases, there are 198 loci in the covering STS map and an additional 145 loci. The physical length is consistent with 11 megabases for 21p and 39 megabases for 21q. With error filtration and allowance for high interference, the genetic length in males corresponds to the chiasma map (54.7 centimorgans), and the genetic length in females is 76.5 centimorgans. The relation between map integration and the STS paradigm is illustrated and discussed. PMID- 8346239 TI - Reversal of muscle differentiation during urodele limb regeneration. AB - Recent studies suggest that maintenance of the differentiated state requires continuous regulation. Limb regeneration in urodele amphibians provides a context in which to address this issue, as limb regeneration may involve the dedifferentiation of multinucleate myotubes to yield mononucleate blastemal cells, which then proliferate and contribute to regenerate tissues. To evaluate this possibility, cultured newt limb myotubes were selectively microinjected with the lineage tracer rhodamine-dextran and introduced into regenerating limbs. In culture, such labeled myotubes were stable after 6-8 weeks, and transfer of the tracer to mononucleate cells was not observed. In contrast, after implantation of labeled myotubes under the wound epidermis of limb blastemas, strongly labeled mononucleate cells were observed after 1 week. These cells could be double labeled with the cytoplasmic lineage tracer and [3H]thymidine that had been incorporated into the nuclei of implanted myotubes. The number of labeled mononucleate cells increased significantly by 2-3 weeks after implantation, indicating that these cells proliferated. Although the fate of these cells at later times was uncertain, we provide evidence consistent with their subsequent differentiation. These results demonstrate reversal in the mononucleate-to multinucleate transition of vertebrate myogenesis. PMID- 8346238 TI - Identification of a precursor genomic segment that provided a sequence unique to glycophorin B and E genes. AB - Human glycophorin A, B, and E (GPA, GPB, and GPE) genes belong to a gene family located at the long arm of chromosome 4. These three genes are homologous from the 5'-flanking sequence to the Alu sequence, which is 1 kb downstream from the exon encoding the transmembrane domain. Analysis of the Alu sequence and flanking direct repeat sequences suggested that the GPA gene most closely resembles the ancestral gene, whereas the GPB and GPE genes arose by homologous recombination within the Alu sequence, acquiring 3' sequences from an unrelated precursor genomic segment. Here we describe the identification of this putative precursor genomic segment. A human genomic library was screened by using the sequence of the 3' region of the GPB gene as a probe. The genomic clones isolated were found to contain an Alu sequence that appeared to be involved in the recombination. Downstream from the Alu sequence, the nucleotide sequence of the precursor genomic segment is almost identical to that of the GPB or GPE gene. In contrast, the upstream sequence of the genomic segment differs entirely from that of the GPA, GPB, and GPE genes. Conservation of the direct repeats flanking the Alu sequence of the genomic segment strongly suggests that the sequence of this genomic segment has been maintained during evolution. This identified genomic segment was found to reside downstream from the GPA gene by both gene mapping and in situ chromosomal localization. The precursor genomic segment was also identified in the orangutan genome, which is known to lack GPB and GPE genes. These results indicate that one of the duplicated ancestral glycophorin genes acquired a unique 3' sequence by unequal crossing-over through its Alu sequence and the further downstream Alu sequence present in the duplicated gene. Further duplication and divergence of this gene yielded the GPB and GPE genes. PMID- 8346240 TI - Target-derived influences on axon growth modes in cultures of trigeminal neurons. AB - Cellular and molecular signals involved in axon elongation versus collateral and arbor formation may be intrinsic to developing neurons, or they may derive from targets. To identify signals regulating axon growth modes, we have developed a culture system in which trigeminal ganglion cells are challenged by various target tissues. Embryonic day 15 (E15) rat trigeminal ganglion explants were placed between peripheral (vibrissa pad) and central nervous system targets. Normally, bipolar trigeminal ganglion cells extend one process to the vibrissa pad and another to the brainstem trigeminal complex. Under coculture conditions, the peripheral processes invade the vibrissa pad explants and form a characteristic circumfollicular pattern. Central processes of E15 ganglion cells invade many, but not all, central nervous system tissues. In isochronic (E15) central nervous system explants such as brainstem, olfactory bulb, or neocortex, these central processes elongate and form a "tract" but have virtually no arbors. However, in more mature targets (e.g., a section from postnatal brainstem or neocortex), they form arbors instead of a tract. We conclude from these observations that whether trigeminal axons elongate to form a tract, or whether they begin to arborize, is dictated by the target tissue and not by an intrinsic developmental program of the ganglion cell body. The explant coculture system is an excellent model for analysis of the molecular basis of neuron-target interactions. PMID- 8346241 TI - The 31-kDa precursor of interleukin 1 alpha is myristoylated on specific lysines within the 16-kDa N-terminal propiece. AB - The cytokine interleukin 1 alpha (IL-1 alpha) is a critical mediator of the immune and inflammatory responses. A unique determinant of its activity as compared with IL-1 beta may be its association with the plasma membrane. While the biologic activity of "membrane IL-1" has been extensively reported, the mechanism of membrane binding remains unclear. We report that the N terminus of the 31-kDa IL-1 alpha precursor is myristoylated on specific internal lysine residues. Immunoprecipitation of [3H]myristic acid-radiolabeled human monocyte lysates with IgG antibodies to the 31-kDa IL-1 alpha precursor recovered a protein with the physicochemical properties of the IL-1 alpha N-terminal propiece (16 kDa, pI 4.45). Glycyl N-myristoylation of this protein is precluded by the absence of a glycine residue at position 2, suggesting that the propiece is myristoylated on epsilon-amino groups of lysine. To determine which lysine(s) are acylated, a series of synthetic peptides containing all lysines found in the IL-1 alpha N-terminal propiece were used in an in vitro myristoylation assay containing peptide, myristoyl-CoA, and monocyte lysate as enzyme source. Analysis of the reaction products by reverse-phase HPLC and gas-phase sequencing demonstrated the specific myristoylation of Lys-82 and Lys-83, yielding predominantly monoacylated product. A conserved sequence in the IL-1 beta propiece was myristoylated with at least 8-fold less efficiency. Acylation of the IL-1 alpha precursor by a previously unrecognized lysyl epsilon-amino N-myristoyl transferase activity may facilitate its specific membrane targeting. PMID- 8346242 TI - Protein oxidative damage is associated with life expectancy of houseflies. AB - The objective of this study was to test some of the predictions of the oxidative stress hypothesis of aging, which postulates that aging is causally associated with the molecular damage inflicted by reactive oxygen species. Protein carbonyl content was used as an index of molecular oxidative modifications. The carbonyl content was found to be associated with the physiological age or life expectancy of flies rather than with their chronological age. Exposure of flies to sublethal hyperoxia (100% oxygen) irreversibly enhanced the carbonyl content of the flies and decreased their rate of oxygen consumption. Results of this study indicate that protein carbonyl content may be a biomarker of aging and support the general concept that oxidative stress may be a causal factor in the aging process. PMID- 8346243 TI - Ultraviolet-induced mutations in Cockayne syndrome cells are primarily caused by cyclobutane dimer photoproducts while repair of other photoproducts is normal. AB - We compared the contribution to mutagenesis in Cockayne syndrome (CS) cells of the major class of UV photoproducts, the cyclobutane pyrimidine dimer, to that of other DNA photoproducts by using the mutagenesis shuttle vector pZ189. Lymphoblastoid cell lines from the DNA repair-deficient disorders CS and xeroderma pigmentosum (XP) and a normal line were transfected with UV-treated pZ189. Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact. After UV exposure and replication in CS and XP cells, plasmid survival was abnormally reduced and mutation frequency was abnormally elevated. After PR, plasmid survival increased and mutation frequency in CS cells decreased to normal levels but remained abnormal in XP cells. Sequence analysis of > 200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers. These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency. However, unlike XP, CS cells are proficient in repair of nondimer photoproducts. Since XP but not CS patients have a high frequency of UV-induced skin cancers, our data suggest that prevention of UV-induce skin cancers is associated with proficient repair of nondimer photoproducts. PMID- 8346245 TI - Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. AB - The existence of water-selective channels has been postulated to explain the high water permeability of erythrocytes and certain epithelial cells. The aquaporin CHIP (channel-forming integral membrane protein of 28 kDa), a molecular water channel, is abundant in erythrocytes and water-permeable segments of the nephron. To determine whether CHIP may mediate transmembrane water movement in other water permeable epithelia, membranes of multiple organs were studied by immunoblotting, immunohistochemistry, and immunoelectron microscopy using affinity-purified anti CHIP IgG. The apical membrane of the choroid plexus epithelium was densely stained, implying a role for CHIP in the secretion of cerebrospinal fluid. In the eye, CHIP was abundant in apical and basolateral domains of ciliary epithelium, the site of aqueous humor secretion, and also in lens epithelium and corneal endothelium. CHIP was detected in membranes of hepatic bile ducts and water resorptive epithelium of gall bladder, suggesting a role in bile secretion and concentration. CHIP was not detected in glandular epithelium of mammary, salivary, or lacrimal glands, suggesting the existence of other water-channel isoforms. CHIP was also not detected within the epithelium of the gastrointestinal mucosa. CHIP was abundant in membranes of intestinal lacteals and continuous capillaries in diverse tissues, including cardiac and skeletal muscle, thus providing a molecular explanation for the known water permeability of certain lymphatics and capillary beds. These studies underscore the hypothesis that CHIP plays a major role in transcellular water movement throughout the body. PMID- 8346244 TI - Rearrangement of sapA homologs with conserved and variable regions in Campylobacter fetus. AB - The Campylobacter fetus surface-layer (S-layer) proteins mediate both complement resistance and antigenic variation in mammalian hosts. Wild-type strain 23D possesses the sapA gene, which encodes a 97-kDa S-layer protein, and several sapA homologs are present in both wild-type and mutant strains. Here we report that a cloned silent gene (sapA1) in C. fetus can express a functional full-length S layer protein in Escherichia coli. Analysis of sapA and sapA1 and partial analysis of sapA2 indicate that a block of approximately 600 bp beginning upstream and continuing into the open reading frames is completely conserved, and then the sequences diverge completely, but immediately downstream of each gene is another conserved 50-bp sequence. Conservation of sapA1 among strains, the presence of a putative Chi (RecBCD recognition) site upstream of sapA, sapA1, and sapA2, and the sequence identities of the sapA genes suggest a system for homologous recombination. Comparison of the wild-type strain (23D) with a phenotypic variant (23D-11) indicates that variation is associated with removal of the divergent region of sapA from the expression locus and exchange with a corresponding region from a sapA homolog. We propose that site-specific reciprocal recombination between sapA homologs leads to expression of divergent S layer proteins as one of the mechanisms that C. fetus uses for antigenic variation. PMID- 8346246 TI - Characterization of an intronless collagen gene family in the marine sponge Microciona prolifera. AB - Two independent clones from the genomic DNA of a marine sponge Microciona prolifera were isolated by hybridization to the Caenorhabditis elegans Col-1 gene and one clone was obtained from genomic DNA by PCR. They contain open reading frames (MpCol1, MpCol2, MpCol3, MpCol4) capable of coding for a family of collagens different from those previously found in sponges. Southern blotting of genomic DNA suggested the presence of several other homologous genes. cDNA clones covering most of the triple-helical coding domain and the 3' untranslated region of MpCol1 were isolated by specific primers and reverse PCR. Two cDNA clones end in the middle of an AATAAA sequence 170 bp downstream from the translation stop codon of MpCol1. The putative NH2-terminal noncollagenous peptide is composed of only seven amino acid residues. The 1074-bp triple-helical coding region is not interrupted by intervening sequences. It codes for a polypeptide of 120 Gly-Xaa Yaa triplets with only one short interruption near the COOH terminus. A putative N-glycosylation sequence (Asn-Gly-Ser), three Arg-Gly-Asp triplets known as cell recognition peptides, frequent Lys residues in the Yaa position (which are templates for hydroxylation), several Lys-Gly-Asn/Xaa-Arg peptides known as the lysyl oxidase recognition site, and long stretches without imino acids could be found within the triple-helical domain. The short COOH-terminal noncollagenous domain closely resembles that of nematode cuticular collagens and vertebrate nonfibrillar collagens. Our results strongly support the idea that the diversity of collagen genes and gene families found in higher organisms already existed in sponge. PMID- 8346247 TI - NF-IL6-mediated transcriptional activation of the long terminal repeat of the human immunodeficiency virus type 1. AB - An upstream control region in the long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) includes a potential negative regulatory element (NRE1). Cotransfecting multimers of a sequence spanning this element with an LTR-CAT construct produced an increase in chloramphenicol acetyltransferase (CAT) activity in Jurkat and HepG2 cells, providing further evidence and support for the existence of an NRE. In screening experiments aimed at identifying those factors that regulate HIV-1 transcription through interactions with the NRE1 region, we isolated a cDNA for NF-IL6. Previous studies have shown that NF-IL6 is a key nuclear factor that activates gene expression in response to interleukin 6. By methylation interference analysis, we have localized the NF-IL6 binding site within the NRE1 region and found that it overlaps an E box that has previously been implicated as the binding element for a negative regulator of HIV-1 expression. Through a database search, we identified an additional consensus binding sequence for NF-IL6 in the LTR of many HIV-1 variants and found that over this sequence, purified NF-IL6 can produce an extended footprint that overlaps one of the binding sites for NF-kappa B. A product of the nf-il6 gene activated transcription from several LTR-CAT constructs in transient transfection assays. Thus, NF-IL6 could play a central role in the control of HIV-1 gene expression and this protein might be a key mediator in signaling pathways where HIV-1 is activated by interleukin 6. PMID- 8346249 TI - Photoaffinity labeling of Torpedo acetylcholine receptor at multiple sites. AB - The acetylcholine receptor from Torpedo californica electroplax was labeled with the photoaffinity reagent bis(3-azidopyridinium)decane perchlorate. All four receptor subunits (alpha, beta, gamma, and delta) were specifically labeled. In the presence of cholinergic agonists the gamma-, beta-, and delta-subunit labeling was decreased significantly, whereas labeling of the alpha subunit was minimally affected. Full occupancy of the two high-affinity sites involving the alpha subunits in the vicinity of alpha-Cys-192-Cys-193 by covalent reaction with bromoacetylcholine also caused a large decrease of gamma-subunit labeling by the photoaffinity reagent and lesser but significant decreases in beta- and delta subunit labeling. No decrease in labeling of the alpha subunit was seen. Labeling of the alpha subunit could, however, be inhibited by high concentrations of the agonist carbamoylcholine. We conclude that the binding sites of high-affinity reside at interfaces of the alpha subunit and other subunits and that the alpha subunit also contributes to formation of a low-affinity site(s) for cholinergic compounds. PMID- 8346248 TI - Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors. AB - The Tax protein, encoded by the human T-cell leukemia virus type I, is a potent activator of viral and cellular gene transcription. Tax does not bind DNA directly but appears to trans-activate through an interaction with host-cell transcription factors that recognize sequences within the promoters of Tax responsive genes. Cellular transcriptional activators implicated in mediating Tax trans-activation include members of the activating transcription factor/cAMP response element binding protein (ATF/CREB) family of proteins, serum response factor, Fos-Jun, and NF-kappa B. Recent evidence suggests that Tax may stimulate human T-cell leukemia virus type I transcription, at least in part, through enhanced binding of ATF/CREB proteins to their recognition elements within the Tax-responsive 21-bp repeats of the viral promoter. In this report, we demonstrate that Tax also enhances the site-specific DNA binding activity of serum response factor and Fos-Jun and modestly enhances the binding of the NF kappa B subunits, p50 and p65. We also show that Tax increases the DNA binding activity of the eukaryotic transcription factors ATF-1, Sp1, and GAL4. These results are consistent with the finding that Tax is highly pleiotropic and suggest that Tax trans-activation may involve enhancement in the DNA binding activity of target transcriptional regulatory proteins. In addition, we show that the mechanism of Tax-enhanced DNA binding activity does not involve an alteration in the redox state of the target protein. PMID- 8346250 TI - CCAAT/enhancer binding protein alpha (C/EBP alpha) undifferentiated protein: a developmentally regulated nuclear protein that binds to the C/EBP alpha gene promoter. AB - During differentiation of 3T3-L1 preadipocytes into adipocytes, transcription of the C/EBP alpha (CCA-AT/enhancer binding protein alpha) gene is activated. The promoter of the C/EBP alpha gene contains a bipartite cis element with binding sites for C/EBP alpha undifferentiated protein (CUP) and an Sp1-like GT box binding protein. Binding of CUP to this element is markedly enhanced by its interaction with the Sp1-like protein. CUP, purified approximately 100,000-fold from HeLa cell nuclear extracts, appears to be composed of at least two types of subunit. Evidence is presented that a CUP-containing protein complex bridges between the CUP/Sp1-like GT box element and a downstream cis element, which contains a C/EBP binding site. During differentiation of 3T3-L1 preadipocytes into adipocytes, CUP activity or expression decreases as expression of C/EBP alpha increases. It is suggested that bridging by the CUP-containing protein complex may play a role in transcriptional regulation of the C/EBP alpha gene. PMID- 8346251 TI - Thyroid hormone-dependent transcriptional regulation of exogenous genes transferred into Xenopus tadpole muscle in vivo. AB - Metamorphosis in amphibians is marked by dramatic thyroid hormone-induced changes that include tail regression. To examine thyroid hormone effects on gene transcription during the early stages of tail resorption, we injected exogenous genes directly into the caudal skeletal muscle of Xenopus tadpoles and followed their expression in vivo. Gene expression was both strong and reproducible, and it correlated with the amount of DNA injected. Moreover, expression continued as long as the animals were blocked in prometamorphosis by antithyroid drugs (for up to 4 months). Thyroid hormone-dependent effects on transcription were examined by using a palindromic thyroid hormone response element linked to a chloramphenicol acetyltransferase reporter gene. Reporter gene expressions were normalized for transfection efficiency by using a constitutively expressed luciferase construct. Physiological concentrations of 3,5,3' triiodo-L-thyronine (1 nM), applied for 120 hr, produced a 5-fold increase in transcription (P < 0.05) from the thyroid hormone response element but did not modify transcription from constitutive viral promoters. This study thus demonstrates that by directly expressing genes in Xenopus tadpole muscle in vivo, one can exploit the powerful experimental advantages of gene transfer systems in an intact, physiologically normal animal. PMID- 8346253 TI - Can a protein influence the fate of its own coding sequence?: the amino- and carboxyl-terminal regions of H1 histone. AB - The amino- and carboxyl-terminal regions of H1 histone are afforded an opportunity to bind to their own coding segments. While such binding is of no consequence to the type of H1 histone that is expressed only in terminally differentiated cells (here referred to as H5), the same binding occurring in H1 of proliferating cells might affect the course of evolution of its amino- and carboxyl-terminal regions. With the above in mind, amino acid sequences of H5 from three species were compared with those of H1 from five species. The spherical core was more conserved in H1 than in H5, whereas the amino- and carboxyl-terminal regions of both were hypervariable. A distinct evolutionary pattern, however, was observed only in these regions of H1 but not of H5. Tandem repeats of short palindromes often generated nearly identical long palindromes in distantly related species. Thus, as far as the 37-residue-long amino-terminal region was concerned, the greatest homology was between the rat and human rather than between the rat and the mouse. With regard to the last 25 residues in the carboxyl-terminal region, the greatest homology was between the chicken and the rainbow trout; the next was between the mouse and the trout. Successions of long palindromes populating the amino- and carboxyl-terminal regions of H1 might be the direct consequence of the autologous binding between peptides and their coding sequence. PMID- 8346252 TI - Increased tolerance to two oomycete pathogens in transgenic tobacco expressing pathogenesis-related protein 1a. AB - Expression of pathogenesis-related protein 1a (PR-1a), a protein of unknown biochemical function, is induced to high levels in tobacco in response to pathogen infection. The induction of PR-1a expression is tightly correlated with the onset of systemic acquired resistance (SAR), a defense response effective against a variety of fungal, viral, and bacterial pathogens. While PR-1a has been postulated to be involved in SAR, and is the most highly expressed of the PR proteins, evidence for its role is lacking. In this report, we demonstrate that constitutive high-level expression of PR-1a in transgenic tobacco results in tolerance to infection by two oomycete pathogens, Peronospora tabacina and Phytophthora parasitica var. nicotianae. PMID- 8346254 TI - Nonreciprocal homologous recombination between Agrobacterium transferred DNA and a plant chromosomal locus. AB - Previously, we demonstrated the occurrence of gene targeting in tobacco cells after Agrobacterium-mediated transformation. In these experiments a defective kanamycin resistance (Kmr) gene residing at a chromosomal location was restored via homologous recombination with an incoming transferred DNA (T-DNA) repair construct (pSDM101) containing a different defective Kmr gene. In this article we describe gene targeting experiments with the same target line, but using an improved repair construct, pSDM321. In one of the Kmr calli obtained after transformation with pSDM321 (line A) the product of homologous recombination was detected using PCR. Further molecular analysis revealed that the defective Kmr gene present on the incoming T-DNA had been restored via homologous recombination with the target locus. The target locus was left unchanged and the corrected T DNA was found to be inserted on the same chromosome but not close to the target locus. This paper presents molecular evidence in plants for the conversion of an introduced DNA molecule (in this case, T-DNA) by a homologous chromosomal locus. PMID- 8346255 TI - Molecular mechanisms of oncogenic mutations in tumors from patients with bilateral and unilateral retinoblastoma. AB - The RB1 gene from 12 human retinoblastoma tumors has been analyzed exon-by-exon with the single-strand conformation polymorphism technique. Mutations were found in all tumors, and one-third of the tumors had independent mutations in both alleles neither of which were found in the germ line, confirming their true sporadic nature. In the remaining two-thirds of the tumors only one mutation was found, consistent with the loss-of-heterozygosity theory of tumorigenesis. Point mutations, the majority of which were C-->T transitions, were the most common abnormality and usually resulted in the conversion of an arginine codon to a stop codon. Small deletions were the second most common abnormality and most often created a downstream stop codon as the result of a reading frameshift. Deletions and point mutations also affected splice junctions. Direct repeats were present at the breakpoint junctions in the majority of deletions, supporting a slipped mispairing mechanism. Point mutations generally produced DNA sequences which resulted in perfect homology with endogenous sequences which lay within 14 bp. PMID- 8346256 TI - Fractionated nuclear extracts from hamster cells catalyze cell-free recombination at selective sequences between adenovirus DNA and a hamster preinsertion site. AB - We have explored the mechanism of adenovirus type 12 (Ad12) DNA integration because of its importance for viral oncogenesis and as an example of insertional recombination. We have used a fractionated cell-free system from nuclear extracts of hamster cells and have partly purified nuclear proteins that could catalyze in vitro recombination. As recombination partners, the 20,880- to 24,049-nucleotide Pst I D fragment of Ad12 DNA and the hamster preinsertion sequence p7 from the Ad12-induced tumor CLAC1 have proven to recombine at higher frequencies than randomly selected adenoviral or cellular DNA sequences. A preinsertion sequence might carry elements essential in eliciting recombination. Patch homologies between the recombination partners seem to play a role in the selection of sites for recombination in vivo and in the cell-free system. Nuclear extracts from BHK21 cells were prepared by incubating the nuclei in 0.42 M (NH4)2SO4 and fractionated by Sephacryl S-300 gel filtration, followed by chromatography on Mono S and Mono Q columns. The purified products active in recombination contained a limited number of different protein bands, as determined by polyacrylamide gel electrophoresis and silver staining. The most highly purified fraction IV had helicase and topoisomerase I activities. We used two different methods to assess the in vitro generation of hamster DNA-Ad12 DNA recombinants upon incubation with the purified protein fractions: (i) transfection of the recombination products into recA- strains of Escherichia coli and (ii) the polymerase chain reaction by using amplification primers unique for each of the two recombination partners. In p7 hamster DNA, the nucleotide sequence 5' CCTCTCCG-3' or similar sequences served repeatedly as a preferred recombination target for Ad12 DNA in the tumor CLAC1 and in five independent cell-free recombination experiments. PMID- 8346257 TI - Detection of recombinations between c-myc and immunoglobulin switch alpha in murine plasma cell tumors and preneoplastic lesions by polymerase chain reaction. AB - Virtually all murine plasmacytomas carry chromosomal translocations that activate c-myc. The predominant (approximately 90%) c-myc-activating chromosomal translocation in pristane (2,6,10,14-tetramethylpentadecane)-induced plasmacytomas in BALB/c mice is a reciprocal translocation t(12;15) in which an immunoglobulin heavy-chain switch sequence is joined to the 5' region of c-myc. The most common switch region involved is S alpha. We developed a direct PCR method to screen for recombinations between c-myc and S alpha. The critical step in establishing the method was the cloning and sequencing of the 5' flank of C alpha, a region with a reduced number of switch repeats that is much more favorable for designing specific PCR primers than the highly repetitive S alpha region. In applying this PCR method, we detected translocation-specific junction fragments in transplanted (10/16, 63%) and primary (5/15, 33%) plasmacytomas. Moreover, the sensitivity of a nested version of that technique allowed us to discern rare t(12;15)s in BALB/c mice in the preneoplastic stage of plasmacytoma genesis (8/20 mice, 40%) as early as 30 days after administration of pristane. We conclude that t(12;15) is the probable primary, if not initiating, oncogenic step in plasmacytomagenesis. PMID- 8346258 TI - Isolation and transmission of the Lyme disease spirochete from the southeastern United States. AB - The isolation of the Lyme disease spirochete (Borrelia burgdorferi) from the southeastern United States is reported. Three isolates, two from cotton mice (Peromyscus gossypinus) and one from the black-legged tick (Ixodes scapularis), were recovered from Sapelo Island, Georgia, in July and September 1991. The spirochetes were characterized by indirect fluorescent antibody assay using a battery of five monoclonal antibodies, by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of whole cell lysates, and by the polymerase chain reaction (PCR) assay using primers for three DNA target sequences found in B. burgdorferi reference strain B-31. Transmission experiments indicate that the three Georgia isolates can infect experimentally inoculated hamsters and mice. Tick transmission of one of the isolates has been attempted so far; I. scapularis transmitted isolate SI-1 from hamsters to mice, but the lone-star tick, Amblyomma americanum, did not. PMID- 8346259 TI - Vpu protein of human immunodeficiency virus type 1 enhances the release of capsids produced by gag gene constructs of widely divergent retroviruses. AB - The Vpu protein of human immunodeficiency virus type 1 facilitates the release of virus particles from the surface of infected cells. The ability of the Vpu protein to facilitate release of Gag proteins from retroviruses that lack a Vpu like protein was examined. The results of these experiments show that Vpu significantly increases the release of the Gag proteins of human immunodeficiency virus type 2, visna virus, and Moloney murine leukemia virus from HeLa cells. The results indicate that Vpu-mediated enhancement of particle release requires neither amino-terminal myristoylation of the Gag precursor nor cleavage of the Gag precursor by the viral protease. The results raise the possibility that Vpu modifies a cellular pathway common to the release of all retroviruses from the cell surface. PMID- 8346260 TI - Long-term depression of glutamate-induced gamma-aminobutyric acid release in cerebellum by insulin-like growth factor I. AB - We tested the possibility that insulin-like growth factor I (IGF-I) acts as a neuromodulator in the adult cerebellar cortex since previous observations indicated that IGF-I is located in the olivo-cerebellar system encompassing the inferior olive and Purkinje cells. We found that conjoint administration of IGF-I and glutamate through a microdialysis probe stereotaxically implanted into the cerebellar cortex and deep cerebellar nuclei greatly depressed the release of gamma-aminobutyric acid (GABA), which normally follows a glutamate pulse. This inhibition was dose-dependent and long-lasting. Moreover, the effect was specific for glutamate since KCl-induced GABA release was not modified by IGF-I. Basic fibroblast growth factor, another growth-related peptide present in the cerebellum, did not alter the response of GABA to glutamate stimulation. In addition, electrical stimulation of the inferior olivary complex significantly raised IGF-I levels in the cerebellar cortex. Interestingly, when the inferior olive was stimulated in conjunction with glutamate administration, GABA release by cerebellar cells in response to subsequent glutamate pulses was depressed in a manner reminiscent of that seen after IGF-I. These findings indicate that IGF-I produces a long-lasting depression of GABA release by Purkinje cells in response to glutamate. IGF-I might be present in climbing fiber terminals and/or cells within the cerebellar cortex and thereby might affect Purkinje cell function. Whether this IGF-I-induced impairment of glutamate stimulation of Purkinje cells underlies functionally plastic processes such as long-term depression is open to question. PMID- 8346261 TI - Segregation of keratinocyte colony-forming cells in the bulge of the rat vibrissa. AB - The epidermis and its related appendages such as the hair follicle constitute the epithelial compartment of the skin. The exact location and distribution of the keratinocyte colony-forming cells within the epidermis or its appendages are unknown. We report that in the rat vibrissa, keratinocyte colony-forming cells are highly clustered in the bulge-containing region. Approximately 95% of the total colonies formed in culture from fractionated vibrissae were in this location and fewer than 4% were located in the matrix area of the follicle. Finer dissection of the bulge-containing region located the colony-forming cells in the small part containing the bulge itself. The segregation of keratinocyte colony forming cells in the bulge confirms the hypothesis that the bulge is the reservoir of the stem cells responsible for the long-term growth of the hair follicle and perhaps of the epidermis as well. PMID- 8346262 TI - Individual variation in contractile cost and recovery in a human skeletal muscle. AB - This study determined the variation among individuals in ATP use during contraction and ATP synthesis after stimulation in a human limb muscle. Muscle energetics were evaluated using a metabolic stress test that separates ATP utilization from synthesis by 31P NMR spectroscopy. Epicutaneous supramaximal twitch stimulation (1 Hz) of the median and ulnar nerves was applied in combination with ischemia of the finger and wrist flexors in eight normal subjects. The linear creatine phosphate (PCr) breakdown during ischemic stimulation defined ATP use (delta PCr per twitch or approximately P/twitch) and was highly reproducible as shown by the relative standard deviation [(standard deviation/mean) x 100] of 11% in three repeated measures. The time constant of the monoexponential PCr change during aerobic recovery represented ATP synthesis rate and also showed a low relative standard deviation (9%). Individuals were found to differ significantly in both mean approximately P/twitch (PCr breakdown rates, 0.29-0.45% PCr per sec or % PCr per twitch; ANOVA, p < 0.001) and in mean recovery time constants (41-74 sec; ANOVA, P < 0.001). This range of approximately P/twitch corresponded with the range of fiber types reported for a flexor muscle. In addition, approximately P/twitch was negatively correlated with a metabolite marker of slow-twitch fiber composition (Pi/ATP). The nearly 2-fold range of recovery time constants agreed with the range of mitochondrial volume densities found in human muscle biopsies. These results indicate that both components involved in the muscle energy balance--oxidative capacity and contractile costs--vary among individuals in human muscle and can be measured noninvasively by 31 P NMR. PMID- 8346263 TI - Change of apparent stoichiometry of proximal-tubule Na(+)-HCO3- cotransport upon experimental reversal of its orientation. AB - Electrogenic cotransport of Na+ with HCO3- has been reported in numerous tissues. It has always been shown with a net transfer of negative charge, but in some situations achieves net outward transport of both species with a stoichiometry of at least three HCO3- ions per Na+ ion (3:1), and in other situations achieves net inward transport of both species and has a stoichiometry of at most two HCO3- ions per Na+ ion (2:1). This suggests either that there may be more than one protein responsible for Na(+)-HCO3- cotransport in different tissues or that if there is a single protein, its stoichiometry may differ depending on the orientation of net transport. The present study, using conventional or double barreled ion-selective microelectrodes to follow basolateral membrane potential and intracellular pH or Na+ activity in Necturus proximal convoluted tubule in vivo, shows that the orientation of the basolateral Na(+)-HCO3- cotransporter can be reversed upon switching from a perfusate simulating normal acid-base conditions to one that imposes peritubular isohydric hypercapnia. Moreover, accompanying the reversal of orientation is a change of apparent stoichiometry from 3:1 to 2:1. Given that the observed change of orientation and accompanying change of apparent stoichiometry occur within seconds and in the same preparation, these results suggest that a single transport protein is responsible for both types of behavior. PMID- 8346264 TI - Cloning and characterization of cDNA encoding glyoxal oxidase, a H2O2-producing enzyme from the lignin-degrading basidiomycete Phanerochaete chrysosporium. AB - Glyoxal oxidase is produced by ligninolytic cultures of the white-rot fungus Phanerochaete chrysosporium and is a source of the extracellular H2O2 that is required by ligninolytic peroxidases. We report here the cloning and characterization of glx-1c cDNA, which encodes glyoxal oxidase. The deduced mature protein has 537 amino acids, a molecular size of 57 kDa, and a pI of 5.1. Five potential N-glycosylation sites are present. The predicted N-terminal sequence is identical to the experimentally determined sequence of purified enzyme and is preceded by a leader peptide of 22 amino acids. The sequence of glx 1c lacks significant homology with known sequences. Specific comparisons were made between the glx-1c translated sequence and that of galactose oxidase from Dactylium dendroides because of previously observed catalytic similarities of the enzyme. Although no significant homology is observed, in both cases extensive beta-sheet regions are predicted from the primary sequences. Glyoxal oxidase activity correlates with transcript levels and is also coordinate with the lignin peroxidases in nutrient nitrogen-starved cultures. PMID- 8346266 TI - A common language for a shared purpose. PMID- 8346265 TI - Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(-)-dependent taurine transporter that is regulated by hypertonicity. PMID- 8346267 TI - How do you put the client's needs first? Aspects of AIDS counselling in nursing. AB - While it is generally accepted that counselling should be client centred, that offered to people with Aids or who are HIV positive tends to be more prescriptive in approach. A study was therefore devised to determine Aids counsellors' concepts of their role and its requirements. PMID- 8346268 TI - Expectations they cannot meet: Understanding postnatal depression. AB - While many medical explanations have been presented to explain the cause of postnatal depression, there is a strong argument that it may be due to psychological distress. Offering mothers a less idealised image of motherhood and greater child care support may help to undermine feelings of dependence, isolation and low self-support, which are known to lead to depression. PMID- 8346269 TI - Improved coordination makes for faster work. Ergonomic analysis of a trauma resuscitation room. AB - It is essential that health professionals feel comfortable in a working environment which enables them to work effectively and efficiently. This study used an ergonomic approach to analyse whether the layout of equipment and materials in a trauma resuscitation unit met its users' needs. PMID- 8346270 TI - Reflexology--its place in modern healthcare. AB - 1. Reflexology is a safe treatment promoting homeostasis. 2. It is an ancient method of healing which is regaining popularity. 3. Reflexology has no side effects, only so-called healing crises--stepping stones to better health. 4. Reflexology is now an established branch of paramedical medicine, and should be available to NHS patients. PMID- 8346272 TI - Radiotherapy skin reactions and treatments. AB - 1. Radiotherapy can often lead to skin reactions of varying severity, yet there has been little research into how these should be treated. 2. A survey was undertaken to find the prevalence of skin reactions and the treatments used. 3. The centres participating in the study use a wide range of treatments for each level of skin reaction. 4. More controlled studies are required to ascertain which treatments are most suitable for each level of reaction. PMID- 8346271 TI - A basis for future action: applying clinical findings of trials on pressure relieving supports to practice. AB - Various research trials have been undertaken to assess the efficacy of pressure relieving aids. The last in a four-part series outlining such trials, this article suggests improvements that can be made to practice in the light of research findings. PMID- 8346273 TI - An issue of sensitivity. Use of analgesic gel in catheterizing women. AB - Catheterisation is an invasive, and often painful procedure for women, yet the use of analgesic gel does not appear to be the norm. It does, however, have a number of benefits for patient and nurse. PMID- 8346274 TI - Working at play. The role of recreation in healthcare. AB - The therapeutic effects of recreation for people with mental health problems in institutions are often ignored by carers and managers. However, with adequate planning, recreation can provide pleasure to both patients and carers, and for the former the benefits extend to their rehabilitation in the community. PMID- 8346275 TI - Bringing purpose to life. The relationship between unemployment and health. AB - It is a common assumption that a person's mental and physical health will suffer during or even under the threat of a period of unemployment. It is important that community healthcare professionals can diagnose to what extent the trauma of unemployment has affected their patients. Only then can appropriate treatment be designed and implemented. PMID- 8346276 TI - Informed choice leads to a satisfactory outcome. Guidelines for choosing a nursing home and residential care. AB - Choosing a nursing home or residential care can be stressful for all concerned. This article outlines the types of homes available, and the financial implications and levels of service to be taken into account. The right choice can only be made if the elderly person and his or her family are aware of all the available options. PMID- 8346277 TI - A right to be heard. PMID- 8346278 TI - A model for calculating tumour control probability in radiotherapy including the effects of inhomogeneous distributions of dose and clonogenic cell density. AB - Most calculations of the biological effect of radiation on tumours assume that the clonogenic cell density is uniform even if account is taken of non-uniform dose distribution. In practice tumours will almost certainly have a non-uniform clonogenic cell density. This paper extends one particular model of tumour control probability (TCP) to incorporate a variable clonogenic cell density while at the same time assuming a constant 2 Gy fraction size and a uniform radiosensitivity throughout the treatment. Since there are virtually no in vivo data on the variation of density we consider some model situations. One clear conclusion is that a large reduction in clonogenic cell density at the edges of a tumour would permit only a very modest decrease in dose if the TCP is not to be reduced. In general the effect on TCP is a complicated function of the variation in both dose and clonogenic cell density. We give the equations which enable both to be included. PMID- 8346280 TI - The measurement of silicon in a lung phantom--a comparison of two nuclear reactions for in vivo activation analysis. AB - The amount of silica in the human lung may be estimated by measurement of silicon using in vivo neutron activation analysis. A pulsed, fast neutron beam, produced with a 2 MV Van de Graaff generator using the 2H + 2H reaction, was used to irradiate a Si-doped chest phantom in order to determine minimum detection limits (MDL). Two 'in-beam' nuclear reactions on Si were studied; prompt fast neutron inelastic scatter 28Si (n,n' gamma)28Si reaction was measured during the beam burst and the slow neutron prompt capture reaction was measured between the fast neutron bursts. Although the latter reaction appeared less favourable due to neutron cross section and measurement efficiency considerations, it yielded an MDL of 1.8 g compared with 2.3 g for the 28Si(n,n' gamma)28Si reaction. A comparison was made with a 252Cf neutron irradiation system where a Si MDL of 6.3 g was obtained using the slow neutron capture reaction. The Van de Graaff system permits 'exposed' Si lung burdens to be measured but not normal levels. Improved measurement sensitivity may be achieved by reduction of high counting-rate losses and high background radiation. PMID- 8346279 TI - The application of correlated sampling to the computation of electron beam dose distributions in heterogeneous phantoms using the Monte Carlo method. AB - Although the Monte Carlo method is capable of computing the dose distribution in heterogeneous phantoms directly, there are some advantages to computing a heterogeneity correction factor. If this approach is adopted there are savings in time using correlated sampling. This technique forces histories to have the same energy, position, direction and random number seed as incident on both the heterogeneous and homogeneous water phantom. This ensures that a history that has, by chance, travelled through only water in the heterogeneous phantom will have the same path as it would have through the homogeneous phantom, resulting in a reduced variance when a ratio of heterogeneous dose to homogeneous dose is formed. Metrics to describe the distributions of uncertainty, efficiency, and degree of correlation are defined. EGS4 Monte Carlo calculation of the dose distribution from a 20 MeV electron beam on water phantoms containing aluminum or air slab heterogeneities illustrate that this technique is the most efficient when the heterogeneity is deep within the phantom, but that improved efficiency can be realized even when the heterogeneity is at or near the surface. This is because some correlation between the two histories is retained despite passage through the heterogeneity. PMID- 8346282 TI - A generalized Gibbs prior for maximum a posteriori reconstruction in SPECT. AB - In this paper, we introduce a Gibbs prior for use in MAP (maximum a posteriori) reconstruction in SPECT. This new prior, with three parameters, is able to approximate the results of previously-proposed priors with two parameters, as well as a continuum of others. Also, it allows the user increased flexibility in selecting the properties to be emphasized in the final reconstructed image estimate. The additional flexibility offered by the new prior is important in addressing the problem of selecting a prior and its associated parameters in a clinical situation. The paper demonstrates the importance of the derivative potential function (DPF) of the Gibbs distribution in determining which properties will be emphasized in the iterated image estimates. The effects of each of the three parameters are demonstrated on reconstructions from acquired SPECT data. We conclude that the parameters must be chosen carefully with consideration for the object distribution and the relative requirements for low contrast detail, smoothing and edge sharpness in the reconstructed image. PMID- 8346281 TI - Dielectric properties of lung tissue as a function of air content. AB - Dielectric measurements were made on lung samples with different electrode systems in the frequency range 5 kHz-100 kHz. In the case of plate electrodes and spot electrodes, the effects of electrode polarization were partly corrected. An air filling factor F is defined, which is determined from the mass and volume of the sample. The results indicate that the electrical properties of lung tissue are highly dependent on the condition of the tissue. Furthermore they show that the conductivity sigma as well as the relative permittivity epsilon r decreases with increasing F. This is discussed using histological material. Using a simple theoretical model, the decrease of sigma and epsilon r is explained by the thinning of the alveolar walls as well as by the deformation of the epithelial cells and blood vessels through the expansion of the alveoli. PMID- 8346283 TI - Determination of both mechanical and electronic shifts in cone beam SPECT. AB - The difference between the displacement of the centre of rotation (mechanical shift, MS) and the electronic centring misalignment (electronic shift, ES) in cone beam SPECT is evaluated. A method is proposed to determine both MS and ES using the centroid of a projected point source sampled over 360 degrees and the Marquardt non-linear fitting algorithm. Both shifts are characterized by two orthogonal components. This method is verified using Monte Carlo simulated point source data with different combinations of mechanical and electronic shifts. Both shifts can be determined correctly. We have also applied the proposed method to our cone beam SPECT system to determine both shifts as well as the focal length. The determined ES parameters are then used to correct the projections and the MS parameters are incorporated into a reconstruction algorithm. The point source images are reconstructed and the image resolutions with and without the shift corrections are measured. The experimental results demonstrate that the image resolution is improved after shift corrections. The experimental results also indicate that the shift parameters determined in the same experiment with the point source located at different places are consistent but change from time to time, suggesting that calibration of the system is needed on a periodic basis. PMID- 8346284 TI - Excision of a trabecular ROI from resin-embedded vertebrae: report on a computer assisted method. AB - A major problem when evaluating the accuracy of quantitative computed tomography (QCT) against chemical analysis of bone mineral is to ensure that the same region of interest (ROI) is measured with two techniques. The method described here attempts to reach this objective. Forty-nine lumbar vertebrae were scanned. The mid-vertebral portion was sawed and embedded in a polyester resin. The ROI defined with an automated contour detection was transmitted, using a Hewlett Packard scanjet, to a computer-assisted milling machine which excised a trabecular ROI sample. The volume of each trabecular sample was determined using an Archimedian method. ROI volumes assessed on QCT were highly correlated with those obtained with the Archimedian method (r = 0.98). The standard error of the estimate was 170 mm3 (4.5%). These results suggest that trabecular samples obtained with this method optimally agree with the ROIs selected on QCT examination. PMID- 8346285 TI - Circadian drinking rhythms in SHR and WKY rats: effects of increasing light intensity. AB - This study sought to define the generality of a previous finding that the spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rat strains differ in free-running circadian period when maintained in running-wheel cages under constant light. Circadian drinking rhythms were monitored in SHRs and WKYs housed without access to running wheels under an increasing series of light intensities beginning with constant darkness. Strain differences in circadian period were seen only at relatively high light intensities, indicating that SHRs and WKYs differ in circadian light sensitivity. Since SHRs and WKYs differ in circadian period with or without access to running wheels, this strain difference is not likely to depend on differential locomotor activity levels. SHRs and WKYs also differed in spectral profile and circadian waveform, but only under low light intensities. At higher intensities, dissociation of rhythmicity was seen in both strains. PMID- 8346286 TI - Effects of amygdaloid lesions on gastric erosion formation during exposure to activity-stress. AB - To examine the role of the amygdala in the production of gastric ulcers induced by activity-stress, electrolytic lesions were placed in the centromedial (CENT) and medial (MED) amygdaloid nuclei, as well as in the intra-amygdaloid division of the bed nucleus of the stria terminalis (BNST). As compared to sham-operated controls (CONT), gastric ulceration was attenuated in rats with CENT lesions and exacerbated in rats with lesions located in the BNST or MED. Wheel running did not differ significantly between control animals and lesioned rats, but did differ within lesioned groups. Rats with MED lesions ran more than rats with CENT or BNST lesions. Results support the view that the integrity of the centromedial amygdala is critical for the maintenance of the viscera and demonstrate that neurogenic factors contribute to the development of gastric erosions during exposure to activity-stress. PMID- 8346287 TI - Wheel running raises body temperature and changes the daily cycle in golden hamsters. AB - The purpose of this study was to characterize the influence of wheel-running activity on temperature circadian rhythm in golden hamsters. Amplitude of body temperature rhythm was significantly higher in animals that had access to the running wheel. Qualitatively, wheel running resulted in squaring of temperature rhythm waveform, a phenomenon that was independent of ambient illumination. When the hamsters had access to an immobilized wheel, the effect on temperature was no longer observed. Fast Fourier Transformation after subtracting 24-h sine waveforms (to rule out harmonics of the principal frequency), indicated distinct secondary components of the rhythms, i.e., a 12-h component in animals that had access to the wheels and an 8-h component in animals that did not. The rise in body temperature could be dissociated from the start of the activity period, body temperature augmenting before the time of light-dark transition, while activity increased about 12 min later. On the first night after presentation of an estrous female, the temperature cycle in male hamsters that did not access to the wheels was similar to that found in animals running on the wheels; the effect was no longer observed in subsequent nights. The results contribute to the view that the spontaneous locomotor activity in hamsters has a significant effect on temperature cycle. PMID- 8346288 TI - Antiaggressive and motor effects of haloperidol show different temporal patterns in the development of tolerance. AB - The study of the temporal course of tolerance development was used as a means to separate different aspects of the action of haloperidol on social behavior. Agonistic behavior was studied in isolated male mice that confronted standard opponents (anosmic and grouped conspecifics) in a neutral area. The aggressive and motor behaviors of the experimental animals were evaluated 30 min or 24 h either after a single injection of haloperidol (0.4 mg/kg) or following the last of a series of 15 or 30 injections. When animals were evaluated 30 min after the haloperidol injection, no tolerance to the antiaggressive effects was evident. The action on immobility, on the contrary, showed a clear tolerance development with repeated drug administration, both with 15 and 30 injections. When evaluated 24 h after the last injection, tolerance to the antiaggressive effects developed with repeated injections. Increased immobility was never found in the tests carried out after 24 h, not even in the single injection group. The clear divergence found in the temporal courses of tolerance to haloperidol in its antiaggressive and motor effects suggests that these actions are mediated through different neurophysiological mechanisms. A parallel with extrapyramidal and therapeutic effects is discussed. PMID- 8346289 TI - Sound levels in rooms housing laboratory animals: an uncontrolled daily variable. AB - High sound levels are known to have adverse effects on the behaviour and physiology of laboratory animals, yet their acoustic environment is rarely monitored. In particular, high-frequency sounds that are above the limit of human hearing, but are well within the limits of many laboratory species (i.e., ultrasounds), are usually ignored. In this study, the acoustic environment of laboratory animals was investigated in a variety of different animal facilities. Sound pressure levels (dB SPL) were monitored for periods up to 24 h over two frequency ranges: a relatively low range (0.01-12.5 kHz), and a high range (12.5 70 kHz). While background sound levels in undisturbed situations were generally low (i.e., below 50 dB SPL), marked increases in sound levels often occurred during the working day, producing characteristic daily variations in the sound profile. Peak SPLs commonly reached values of 80-95 dB in the low-frequency range and 50-75 dB in the higher range. In most cases, sound levels were low over weekends. The results suggested that human activities were a very important source of sound in most animal facilities. In a few situations (e.g., rabbits, marmosets, dogs), the animals themselves provided a significant contribution to the acoustic environment. It is clear that the acoustic environment of laboratory animals is a daily variable that is usually uncontrolled and that may have important implications for behavioural and physiological experiments and for animal welfare. PMID- 8346290 TI - The role of the lateral septum in anxiolysis. AB - Behavior of rats in the water-lick conflict test was examined during stimulation, and after lesions of the lateral septal nucleus. Continuous low-current stimulation resulted in an anxiolytic effect, an increase in the number of licks, and hence in the number of shocks, during a signaled, punished period. This effect is similar to the one seen with peripheral administration of benzodiazepine and other anxiolytic agents. Rewarding medial forebrain stimulation did not have this effect. Conversely, septal lesions resulted in an anxiogenic effect, a significant decrease in the number of licks during the punished period. Lesions had this effect when the conflict behavior was already well established. Septal lesions performed before acquisition of the conflict behavior resulted in initial retardation of acquisition. The results suggest an important role for the lateral septum in the inhibition of anxiety and in the acquisition of behaviors reinforced by alleviation of anxiety. PMID- 8346291 TI - Sex differences and gonadal hormones influence susceptibility to the activity stress paradigm. AB - The present study investigated the effect of gonadal hormones on activity, food consumption, severity of ulceration, weight loss, and survival duration in male and female rats exposed to the activity-stress (A-S) paradigm. Animals received either sham surgery or gonadectomy and were housed in activity wheels or standard suspended cages. Results indicated that gonadectomized animals were more likely to engage in high running levels in the A-S paradigm; in addition, castrated males developed significantly more ulceration than the other groups. Neither sex nor gonadectomy affected the survival duration of A-S animals. PMID- 8346292 TI - Deprivation alters rats' flavor preferences for carbohydrates and fats. AB - The effects of food deprivation on rats' preferences for the flavors of different macronutrients were investigated. To minimize postingestive influences on flavor preferences, brief test sessions (30 min) and calorically dilute (0.08 kcal/g) solutions or suspensions were used. The findings revealed that whereas nondeprived rats preferred sucrose (2%) to hyrolyzed starch (2% Polycose), food deprived rats strongly preferred Polycose to sucrose. Deprived rats also acquired a preference for a cue flavor paired with Polycose, while nondeprived rats preferred a sucrose-paired cue flavor. Food deprivation also caused rats to switch their preferences from sucrose to corn starch, and from sucrose to corn oil. Food deprivation did not, however, alter the rats' preference for Polycose over corn starch, and it blocked, but did not reverse, their preference for Polycose over corn oil. Taken together, the findings indicate that food deprivation enhances the preference for palatable nonsweet nutrients (Polycose, corn starch, corn oil) over a sweet nutrient (sucrose). This effect was specific to food deprivation; water deprivation did not reverse the rats' preference for sucrose to Polycose. PMID- 8346293 TI - Persistent plasma cholesterol elevations are produced by one or three stressor exposures in rats fed a normal laboratory diet. AB - Typically, stress-related elevations in rat plasma cholesterol (CHOL) require preexposure to diets high in fats or cholesterol and lengthy stressor protocols. We report on two studies in which we measured plasma CHOL 22-h poststressor in rats fed Purina Laboratory Rodent Chow and exposed to 3 (3-day) or 1 (1-day) daily stressor sessions [40, 2 mA tailshocks]. In the first study, both the 3-day and 1-day groups exhibited moderately elevated morning plasma CHOL 22-h poststressor compared to nonshocked controls. Along with the groups in the first study, a second study included a restricted food control, rats transferred to the stressor environment, and rats simply transferred to an adjacent room. Neither restricted feeding nor the room transfers had an effect on morning plasma CHOL. However, the 3-day and 1-day groups again exhibited moderately elevated CHOL. Previous reports did not find elevated plasma CHOL in rats given a single stressor exposure when sampled at the end of the stressor session. Thus, the persistently elevated morning CHOL exhibited by the 1-day group may develop over time. The relatively slow development of plasma CHOL elevations may be related to the time course of stressor-induced thyroid suppression. PMID- 8346294 TI - Evidence for a separate food-entrainable circadian oscillator in the pigeon. AB - In Experiment 1, four pigeons lived in a metabolic chamber on a 12h:12h LD cycle where they maintained a reduced body weight by consuming a daily ration of food presented at the eighth hour of the photophase. Body temperature (Tb) and oxygen consumption (Vo2) increased prior to the daily feeding. The possibility that a food-entrainable oscillator timed these anticipatory responses was tested by four manipulations, conducted in successive phases, each of which involved eliminating the regularly scheduled food presentation, which is the putative entraining stimulus for such an oscillator, while the 12h:12h LD cycle remained in effect. The manipulations, and their outcomes, were: when fasting was imposed for 3 days, the anticipatory responses continued to occur; when ad lib feeding was allowed for 11 days, the anticipatory responses were mostly eliminated; when fasting was reimposed for 5 days, there was evidence that the anticipatory responses reoccurred; and, when the time of the daily feeding was phase-shifted earlier in the photophase for 8 days, anticipatory responses persisted at the original feeding time and simultaneously developed at the new feeding time. In the first phase of Experiment 2, key pecking by two pigeons produced food only during hours 9-11 of the daily photophase (12h:12h LD). In this condition, Tb increased and key pecking occurred in anticipation of the daily period of food availability. Evidence for a food-entrained oscillator was sought in a second phase when constant dim light (LL) was imposed without changing the hours of food availability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346295 TI - Biotelemetry: adjustment of a telemetry system for simultaneous measurements of acute heart rate changes and behavioral events in unrestrained rats. AB - The radiotelemetry system described in this paper consists of an implantable transmitter and a receiver, connected to a microcomputer. The hardware and software belonging to Mini-Mitters, for the collection and analysis of heart rate (HR), core temperature (CT), and gross activity data, do not possess the flexibility to detect acute changes in HR nor to discriminate among simultaneously occurring different types of behavior. In order to study short term changes in HR in response to stress or drugs, in relation to behavioral responses, an inexpensive computer interface and a software program (CARDIAQ) were developed to collect data from Mini-Mitters. The interface conveys the QRS signal, which is converted to a TTL pulse train, to the parallel printer adapter (LPT1) of an IBM-compatible computer. Heart rate is determined by measuring single interbeat intervals (IBI). The software controls the sampling schedule and stores the collected data in a format compatible with a commercial spreadsheet package. The program calculates the median IBI per s, mean +/- SD IBI, variance, skewness, and kurtosis of the IBI distribution. In addition, it enables simultaneous recording of behavior by entering data through the keyboard at the occurrence of each event. In this paper, we describe the CARDIAQ program and provide examples of its application together with the implantable transmitters in freely moving rats. PMID- 8346296 TI - The effects of the spontaneous ingestion of particular foods or beverages on the meal pattern and overall nutrient intake of humans. AB - The influence of the ingestion of particular beverages and foods on the overall nutrient intakes and meal patterns of humans was investigated by paying 323 adults to maintain 7-day diaries of everything they ingested, time of ingestion, and subjective and social conditions. Ingestion of noncaloric beverages, diet sodas, and coffee or tea, were associated with low overall intakes but were not found to influence the amount eaten over the course of the day or in individual meals. Fifteen different caloric containing drink or food types were found, in general, to add to the total calories ingested in meals or over the day without displacing calories ingested in other forms. The results indicate that individual foods or beverages are ingested independent of other constituents and that intake within meals or over the entire day is elastic and readily influenced by nonregulatory factors. PMID- 8346297 TI - Effect of photoperiod on the development of wheel-running activity rhythms in LEW/Ztm rats. AB - Wheel-running activity of LEW/Ztm rats is characterized by a multimodal pattern consisting of two activity bouts about 3-5 h apart. In this study we investigated the development of activity rhythms in LEW rats born and raised under three different photoperiods (LD 18:6, LD 12:12, and LD 6:18). Wheel-running activity was measured for 6 weeks in LD and for another 6 weeks in constant darkness (DD). The length of the photoperiod influenced the phase relationship between the two activity bouts only during the first week after weaning. Then, the characteristic activity pattern was established independently of the length of the photoperiod. However, development under long photoperiods (LD 18:6) resulted in a temporary increase in the level of activity and a significant shortening of the free running period under DD. These results indicate that the multimodal activity pattern displayed by LEW rats is controlled by separate activity oscillators that establish their unique phase relationship early during development. PMID- 8346298 TI - Restoration of staggerer mouse maternal behavior following long-term breeding selection. AB - Two lines of staggerers from the C57BL/6 strain were tested for disturbances in maternal behavior and locomotion. One line, called Pasteur, included staggerers available at L'Institut Pasteur. The second line, called Selected, included staggerers that had been bred in our laboratory for several generations for their ability to reproduce. While none of the Pasteur animals showed any evidence of maternal behavior, most of the Selected mutant mice became maternal, carrying about 90% of the pups until weaning. No group differences were seen in locomotory behavior. It was concluded that a) as a result of long-term breeding selection, homozygous (sg/sg) animals of the C57BL/6 strain may be able to exhibit maternal behavior from birth on, even under standard laboratory conditions; b) the restoration of the maternal behavior does not equally affect all components of this behavior pattern; and c) the impairment of the maternal behavior showed by the staggerer females is not a necessary consequence of impaired locomotory capacity characteristic of the staggerer. PMID- 8346299 TI - Aggressive behaviour in immature captive Nile crocodiles, Crocodylus niloticus, in relation to feeding. AB - This study presents five aspects of aggressive behaviour in juvenile Nile crocodiles, Crocodylus niloticus, as observed in five cohorts of 6-18 month-old animals. During this period, the animals grew from a range of 35-55 cm, to a range of 65-115 cm. 1) Stock density related to aggression: decrease in density resulted in significant decrease in the frequency of agonistic events, with 0.64 events/100 crocodiles/min observed in a density of 6.7 crocodiles/m2, compared to 0.26 events/100 crocodiles/min observed in a density of 4.7 crocodiles/m2. 2) Aggression during feeding: in all five groups, there was a significantly higher level of aggression during feeding times. 3) Aggression related to body size: the largest crocodiles were the most aggressive group in agonistic events, mainly against the smallest ones. The largest group, the medium sized, was the least involved in agonistic events. 4) Aggression related to food preference: crocodile food preference was live fish > live chicks > dead fish > ground meat. Except for one food type (live chicks), a significant (p < 0.05) correlation was found between food preference and feeding related aggression in the prey diet groups. 5) Aggression related to an artificial selection for size: removal of the largest crocodiles (which formed 30% of the stock) from the population caused a dramatic decrease in all forms of aggressive behaviour. PMID- 8346300 TI - A noninvasive strategy for identifying and quantifying innocuous and nociceptive peripheral afferent activity evoked by nerve stimulation. AB - This study evaluated the utility of the compound nerve action potential (CAP) and spinal nociceptive withdrawal (R3) reflex in identifying and quantifying peripheral afferent activity evoked by sural nerve stimulation in humans. The results of this work demonstrate that currents less than or equal to that which elicits a just-maximal CAP can be considered purely innocuous; provide further evidence that the R3 is an objective means of identifying noxious stimulus levels; and suggest that current provides the best noninvasive quantitative estimate of afferent activity throughout the innocuous and noxious range. This work also demonstrates that some of the individual variability in the psychophysical function can be attributed to peripheral factors that affect the amount of current reaching the nerve. It is important, therefore, that these peripheral factors be considered when studying individual differences in the psychophysical function generated by electrical stimulation. PMID- 8346302 TI - Hypergastric acid secretion in rats with ventromedial hypothalamic lesions. AB - This study was designed to investigate abnormal gastric acid secretion in ventromedial hypothalamic (VMH)-lesioned rats. Basal secretion and secretion stimulated by pentagastrin (25 micrograms/kg, IP) or histamine (2 mg/kg/h, IV) were significantly higher in VMH-lesioned rats than in sham VMH-lesioned rats. Subdiaphragmatic vagotomy and methyl atropine treatment (5 mg/kg, IV) remarkably decreased both basal (about 36-44%) and stimulated secretion (about 36-67%) in VMH-lesioned rats, but did not completely reverse it to normal. Serum insulin and glucose levels were significantly higher in VMH-lesioned rats, but serum gastrin levels were not. VMH-lesioned rats showed significantly heavier gastric dry weight; however, no difference in the mucosal layer/total layer ratio of the gastric wall and the density of the parietal cells was observed between the two groups, indicating that the total number of parietal cells might have increased in VMH-lesioned rats because the increase of gastric dry weight can be presumed to be due to increase of the gastric mucosal layer as well as total layer. These results suggest that vagal activation is one of the main contributors to hypergastric acid secretion in VMH-lesioned rats, but that other factors such as increase of parietal oxyntic cell number may also contribute. PMID- 8346301 TI - Exercise endurance in rats: roles of type I and II corticosteroid receptors. AB - Intact and adrenalectomized (ADX) rats were mildly food deprived and administered dexamethasone (type II agonist), aldosterone (type I agonist), corticosterone (mixed agonist), or vehicle 24 and 2 h prior to forced exercise in a treadmill. The endurance of intact animals was unaffected by hormone treatments. Adrenalectomy greatly advanced the onset of fatigue, and aldosterone exacerbated the effect of adrenalectomy. Corticosterone improved endurance in ADX rats, and dexamethasone was even more potent in this respect. Aldosterone slowed deprivation-induced weight loss in ADXs, while corticosterone and especially dexamethasone accelerated loss. Thus, endurance was directly related to body weight loss, and presumably to the fuels released by such loss. The results extend the type I-type II functional dichotomy to the delivery of utilizable energy for metabolically active tissues. PMID- 8346303 TI - Responsiveness to testosterone of male gerbils from known intrauterine positions. AB - Following either a) castration or b) both castration and implantation with capsules releasing a constant, physiological dose of testosterone, adult male Mongolian gerbils that had matured in intrauterine positions between two male fetuses still scent marked with greater frequency than did male gerbils that had matured in intrauterine positions between two female fetuses. We also found significant positive correlations between the relative frequency of scent marking exhibited by individual male gerbils when intact, after castration and after both castration and implantation with capsules releasing testosterone. Each of these findings is consistent with the view that differential exposure to testosterone, as a consequence of fetal intrauterine position, has lasting effects on the organization of scent-marking by male gerbils. PMID- 8346304 TI - Validation study of a total body electrical conductive (TOBEC) instrument that measures fat-free body mass. AB - Validation of the model SA-2's (EM-SCAN, Inc.) ability to measure fat-free body mass (FFM) and indirectly predict body fat mass using total body electrical conductivity (TOBEC) methodology was investigated. To simulate changes in FFM (6.8 to 27.2 g) and fat mass (5 to 20 g), saline and oil, respectively, were injected into multiple sites of male Sprague-Dawley rats in separate trials. Two identical experiments were conducted; only the body weights differed. In Experiment 1 the rats' starting body weight averaged 171.8 +/- 3.4 g, while it averaged 214.0 +/- 2.8 g in Experiment 2. In Experiments 1 and 2, model SA-2 was used, and theoretical changes in FFM had correlations of r = 0.88 and r = 0.82, respectively. There was a tendency of the machine to consistently overpredict FFM as greater amounts of saline were injected. In Experiment 1, when oil was injected, FFM remained extremely stable, whereas in Experiment 2, it consistently overpredicted the amount of fat added in these heavier rats. Because the overpredictions in both the cases were consistent, an adjustment to the prediction equation can possibly correct these problems. Until this is done, caution must be used in interpreting data gather from the model SA-2. PMID- 8346305 TI - Measurement of body composition of live rats by electromagnetic conductance. AB - Measurement of body composition in vivo is important in many nutritional studies. One method for estimating body composition is total body electrical conductance (TOBEC). The TOBEC methodology is based on measuring changes of an electromagnetic field that are proportional to lean body mass (LBM). Sprague Dawley rats (n = 117) ranging in age from 49 to 105 days were measured by TOBEC, and the TOBEC results were compared with direct carcass chemical analyses. The rats ranged in weight from 155 to 500 g. Mean LBM was 92.4% of total body weight (b.wt.), and mean body fat was 7.4% of total b.wt. Mean hydration of LBM was 71.7% and decreased (r = -0.59, p < 0.0001) with age. Using the manufacturer's supplied equation, TOBEC measurement underestimated actual LBM by 12% (p < 0.0001). As a consequence of this error, a new prediction equation was generated using half of the data set, and this equation was cross-validated with the other half of the data set. The mean LBM calculated from the new prediction equation was not different from chemically determined LBM, but the estimated percent body fat of some rats was negative. Thus, TOBEC may be useful in predicting mean LBM of a population, but this indirect method may lack the sensitivity to provide accurate estimates of body composition of an individual. PMID- 8346306 TI - Electrophysiological and behavioral correlates of sleep in the blackbird (Turdus merula). AB - Sleep in five blackbirds was investigated by continuous 24-h recordings of EEG, EOG, EMG, HR, and behavior. Because these recordings were similar in many respects to those obtained previously in other species, it was possible to define the electrophysiological correlates of active wakefulness (AW), quiet wakefulness (QW), slow wave sleep (SWS), and paradoxical sleep (PS). The time spent in SWS and PS was 32.2% and 5.7% of the 24-h period, respectively. The amount of SWS decreased during the course of the dark period, whereas PS exhibited an increasing trend. In addition, SWS always preceded PS, as in mammals. Thus, homeotherms may share common mechanisms of sleep regulation. Blackbirds turned their heads so that their beaks pointed backwards only during darkness. This back posture was usually associated with sleep. Head nodding, which occurred only when the beak pointed forward, was observed during 13% of PS episodes. Eye closure was a reliable behavioral index of sleep. Detailed behavioral observations alone do not provide sufficient information for the accurate assessment of sleep stages in blackbirds. PMID- 8346307 TI - Lack of potassium-anion interaction in diet selection by captive meadow voles. AB - An experiment was conducted to test whether selective avoidance of high-potassium diets by captive meadow voles (Rodentia: Microtus pennsylvanicus) depends on the anions with which potassium is associated. Voles were presented simultaneously with a) low- and high-potassium diets formulated with either potassium sulfate, potassium chloride, or a mixture of potassium chloride and potassium citrate; or b) paired combinations of high-potassium diets containing different anions. In the first part of the experiment, voles preferentially selected the low-potassium diets, with the degree of selectivity virtually completely independent of the associated anion. These results confirm previous suggestions that potassium avoidance may be a component in diet selection by herbivores, especially during spring and summer. There is only weak indication that anion content affects selection of diets with fixed potassium content. PMID- 8346308 TI - A rat model for attention deficit-hyperactivity disorder. AB - A number of animal models for attention deficient-hyperactivity disorder (ADHD), a common childhood disorder, have been developed. However, none of these models are truly representative of naturally occurring developmental ADHD. In such models, hyperactivity is induced by electrical or chemical brain lesions, by pharmacological manipulation, or by genetic breeding that is coupled with hypertension. Based on the observation that some hyposexual rats also are hyperactive, we have studied these rats in order to determine whether they portray characteristics representative of ADHD. Results of open field testing, response to stimulant medication challenge, and measurement of the rat's ability to block irrelevant information in a conditioned avoidance response demonstrate three properties characteristic of ADHD: a) a high level of spontaneous motor activity; b) an attenuation of motor activity in response to amphetamine; and c) a deficit in selective attention. These data indicate that these rats may be a model for the study of ADHD. PMID- 8346310 TI - Effects of bombesin on temporal patterns of ingestion in the rat. AB - Bombesin, an analog to gastrin releasing peptide, has previously been shown to inhibit food intake in the rat. In order to further characterize the effects of bombesin on ingestive behavior, the present study examined licking patterns of rats drinking sweetened condensed milk following bombesin (4 micrograms/kg, IP) or vehicle injection under two levels of food deprivation (0 and 24 h). Both bombesin treatment and satiety (reducing food deprivation from 24 to 0 h) significantly decreased total milk consumption during a 1-h test. Analysis of licking patterns suggested that bombesin and satiety operate by similar but not identical mechanisms. Deprivation reduction tended to decrease ingestion by reducing the rate of drinking and size of the first meal. Bombesin, by contrast, reduced the total duration of drinking and the number of meals taken, but had no effect on lick rate. Cumulative intake records suggested that bombesin reduces the volume threshold for termination of drinking such that intake continues at a normal rate below this threshold but ceases above it. This bombesin-imposed threshold for cessation of drinking was between about 5 and 7 ml for individual animals under both food-deprived and nondeprived testing conditions. PMID- 8346309 TI - Effect of life in a constant light environment on the course of hypertension in Dahl rats. AB - An important goal for biobehavioral scientists is to evaluate treatments that might extend life in the presence and absence of disease. The prototypic example of such a treatment is food restriction. Importantly, we have shown that exposure to a life-long environment of constant light extends life in hamsters with severe, life-threatening heart disease. The purpose of this experiment was to determine whether constant light would also extend the life of rats with an inherited form of hypertension. Constant light neither delayed the progression of hypertension nor extended life in this model. These data suggest that constant light may have a more limited use as an experimental therapeutic modality to extend life as compared to food restriction. PMID- 8346311 TI - Context conditioning: positive reinforcing effects of various food-related stimuli. AB - Rats were subjected to context preference tests to investigate the degree to which various manipulations involving food stimuli can be used to appetitively condition contextual cues. One manipulation consisted of placing hungry rats in a context that contained food that they could consume. A second one involved exposure to a context containing food that could only be seen and smelled, without consumption being possible. A third type of manipulation consisted of exposing animals to a context after the consumption of a small meal in the home cage. Finally, hungry, control subjects were merely exposed to a context containing an empty food tray. Preference for the context was only enhanced after the first type of manipulation, indicating that the actual consummatory act constitutes the major source of reinforcement in the present procedure. Olfactory and visual food cues, as well as postingestional aftereffects in isolation, did not function as reinforces. PMID- 8346312 TI - Short-term oral sensory deprivation: possible cause of binge eating in sham feeding dogs. AB - Six mongrel dogs (18-20 kg) were prepared with gastric and esophageal fistulas. All dogs were studied under four experimental conditions. In conditions 1 and 3 the dogs were allowed to sham feed either a high-palatable or low-palatable meal on days 1-5 followed by a sham feed of a high-palatable or low-palatable meal on day 6. In conditions 2 and 4 the dogs were not sham fed (oral sensory deprived) on days 1-5 but were allowed to sham feed either a high-palatable or low palatable meal on day 6. Total caloric requirement during each 6-day study was given by infusion of a liquid diet (Isocal) through the gastric fistula following the experiment. In condition 4, dogs deprived of oral sensation on days 1-5, significantly overconsumed their low-palatable meal on day 6. In condition 2, dogs deprived of oral sensation on days 1-5 also overconsumed their high palatable meal on day 6, although this did not reach statistical significance. Dogs that received oral stimulation days 1-5 (conditions 1 and 3) did not overconsume their high- and low-palatable meals on day 6, suggesting that binge eating following short-term oral deprivation may be avoided if the diet provides adequate oral sensory stimulation. Body weights were well maintained throughout each study period and no changes were observed. PMID- 8346314 TI - Preoperative skin preparation of patients. PMID- 8346313 TI - Modulation of the satiety effect of cholecystokinin by estradiol. AB - Data obtained from a wide variety of mammalian species indicate that feeding behavior can be influenced by changes in endogenous estrogens and by exogenous estrogenic treatments. The present experiment represents an initial investigation of the hypothesis that the suppression of food intake by estradiol is mediated by an enhancement of the satiety effect of cholecystokinin (CCK). Twenty-four female rats were ovariectomized and implanted either with a 5% estradiol silastic capsule or an empty capsule on the day of surgery. Three weeks later, animals received IP injections of CCK-octapeptide (5.0 or 10.0 micrograms/kg) or saline after 24-h food deprivation. Food and water intake were measured 60 min after treatment. Although CCK suppressed feeding in all subjects, the effects on food intake were greater in estradiol-treated females. CCK injections also reduced water intake, but there was no interaction between estradiol and CCK on drinking. These findings indicate that the inhibitory effect of CCK on food intake is enhanced in females treated with a physiological dose of estradiol, and suggest that the effects of estradiol on feeding behavior may be mediated by a potentiation of the satiety effect of CCK. PMID- 8346315 TI - Making a video about facial disfigurement: a challenging process. PMID- 8346316 TI - Laser surgery. PMID- 8346317 TI - The American Disabilities Act: a guide to implementing in the plastic surgical setting. PMID- 8346318 TI - The role of the literature review in research. PMID- 8346319 TI - Psychological factors in cosmetic plastic surgery: recent developments in patient care. AB - The goal of cosmetic surgery is to facilitate improvement in the patient's psychological functioning primarily by modifying the patient's body image. This article updates the professional literature on recent developments in the study of the psychology of cosmetic plastic surgery. PMID- 8346320 TI - Psychological adjustment to hand injuries: nursing management. AB - Traumatic hand injuries can be devastating experiences both physically and psychologically. The plastic surgery nurse who can identify the various responses that routinely occur with hand injured patients is better prepared to normalize their experiences and implement the necessary interventions toward overall rehabilitation. This article will provide an overview of specific characteristics and emotional reactions following hand injuries, factors that influence adjustment, and nursing management that promotes optimal recovery. PMID- 8346321 TI - A woman's psychological response and adjustment to the breast cancer diagnosis. AB - The permanent loss of a breast from cancer brings forth a range of emotional and behavioral reactions. As more and more women opt for immediate breast reconstruction, plastic surgical nurses need to recognize the acute stress reactions these patients are experiencing. Not only should the disease itself be treated, but the individual suffering from the disease. This article provides an overview of women's psychological responses and adjustments to the breast cancer diagnosis that plastic surgical nurses need to consider. PMID- 8346322 TI - A less-than-perfect experience. AB - Plastic surgical nurses frequently work with pediatric patients who have physical or cognitive differences. In a society that puts such high value on physical appearance and perfection, these children are vulnerable to discrimination. Parents and children look to the plastic surgical nurse for support and acceptance. PMID- 8346323 TI - Social service collaboration: meeting the patient's psychosocial needs. AB - Plastic surgical nurses and social workers can collaborate to meet their patient's psychosocial needs. Patients and their families benefit from access to social services intervention and resources. PMID- 8346324 TI - The effects of dieting on eating behavior: a three-factor model. AB - I review and critique restraint theory and develop a 3-factor model of dieting behavior. The factors--frequency of dieting and overeating, current dieting, and weight suppression--are embedded within a 3-dimensional grid that also considers mechanisms mediating the effects of dieting and the influence of weight status. I argue that the eating behavior exhibited by restrained eaters stems from their frequent dieting and overeating in the past rather than from their current state of dietary or cognitive restraint. Evidence is reviewed, indicating that current dieting and weight suppression have different effects on eating than does restraint. The 3-factor model is used to reinterpret findings consistent with restraint theory and to explain findings inconsistent with restraint theory. Finally, clinical and research implications of the 3-factor model are discussed. PMID- 8346325 TI - Do people know how others view them? An empirical and theoretical account. AB - Meta-accuracy is the extent to which people know how others see them. Following D.A. Kenny and L. Albright (1987), we show how the social relations model (SRM) can be used to investigate meta-accuracy. The results from 8 SRM studies involving 569 subjects are reviewed. We argue that people determine how others view them not from the feedback that they receive from others but from their own self-perceptions. Consistent with this argument are the findings that (a) people overestimate the degree of consistency in the ways that different targets view them and (b) people are better at understanding how others generally view them than how they are uniquely viewed by specific individuals. PMID- 8346326 TI - The problem of equivalent models in applications of covariance structure analysis. AB - For any given covariance structure model, there will often be alternative models that are indistinguishable from the original model in terms of goodness of fit to data. The existence of such equivalent models is almost universally ignored in empirical studies. A study of 53 published applications showed that equivalent models exist routinely, often in large numbers. Detailed study of three applications showed that equivalent models may often offer substantively meaningful alternative explanations of data. The importance of the equivalent model phenomenon and recommendations for managing and confronting the problem in practice are discussed. PMID- 8346327 TI - Gender differences in sexuality: a meta-analysis. AB - This meta-analysis surveyed 177 usable sources that reported data on gender differences on 21 different measures of sexual attitudes and behaviors. The largest gender difference was in incidence of masturbation: Men had the greater incidence (d = .96). There was also a large gender difference in attitudes toward casual sex: Males had considerably more permissive attitudes (d = .81). There were no gender differences in attitudes toward homosexuality or in sexual satisfaction. Most other gender differences were in the small-to-moderate range. Gender differences narrowed from the 1960s to the 1980s for many variables. Chodorow's neoanalytic theory, sociobiology, social learning theory, social role theory, and script theory are discussed in relation to these findings. PMID- 8346328 TI - Source monitoring. AB - A framework for understanding source monitoring and relevant empirical evidence is described, and several related phenomena are discussed: old-new recognition, indirect tests, eyewitness testimony, misattributed familiarity, cryptomnesia, and incorporation of fiction into fact. Disruptions in source monitoring (e.g., from confabulation, amnesia, and aging) and the brain regions that are involved are also considered, and source monitoring within a general memory architecture is discussed. It is argued that source monitoring is based on qualities of experience resulting from combinations of perceptual and reflective processes, usually requires relatively differentiated phenomenal experience, and involves attributions varying in deliberateness. These judgments evaluate information according to flexible criteria and are subject to error and disruption. Furthermore, diencephalic and temporal regions may play different roles in source monitoring than do frontal regions of the brain. PMID- 8346329 TI - Long-term consequences of childhood physical abuse. AB - This article reviews the literature on the long-term consequences of childhood physical abuse. Empirical research is discussed within 7 topic areas: aggressive and violent behavior, nonviolent criminal behavior, substance abuse, self injurious and suicidal behavior, emotional problems, interpersonal problems, and academic and vocational difficulties. The studies reviewed involve primarily adult populations, although pertinent findings from literature on children and adolescents are briefly summarized. Some variables that affect the relation between physical abuse and long-term consequences are examined. These moderator variables include maltreatment characteristics, individual factors, family factors, and environmental factors. The article ends with suggestions for future research on long-term consequences and variables that may affect these outcomes. PMID- 8346330 TI - Context, time, and memory retrieval in the interference paradigms of Pavlovian learning. AB - In this article I review research and theory on the "interference paradigms" in Pavlovian learning. In these situations (e.g., extinction, counterconditioning, and latent inhibition), a conditioned stimulus (CS) is associated with different unconditioned stimuli (USs) or outcomes in different phases of the experiment; retroactive interference, proactive interference, or both are often observed. In all of the paradigms, contextual stimuli influence performance, and when information is available, so does the passage of time. Memories of both phases are retained, and performance may depend on which is retrieved. Despite the similarity of the paradigms, conditioning theories tend to explain them with separate mechanisms. They also do not provide an adequate account of the context's role, fail to predict the effects of time, and overemphasize the role of learning or storage deficits. By accepting 4 propositions about animal memory (i.e., contextual stimuli guide retrieval, time is a context, different memories are differentially dependent on context, and interference occurs at performance output), a memory retrieval framework can provide an integrated account of context, time, and performance in the various paradigms. PMID- 8346331 TI - Festschrift issue honoring Donald Oken, M.D. PMID- 8346332 TI - Coping theory and research: past, present, and future. PMID- 8346333 TI - Life events and affective disorder: replications and limitations. AB - Previously unpublished analyses from two longitudinal inquiries are presented that use a contextual approach to rating the meaning of life events based on intensive semistructured interviews. The studies concern the longstanding question of specific versus general susceptibility in disease causation. The first study is based on a general population sample of 400 women and deals with the specificity of meaning of events provoking clinical depression and anxiety disorders. The second is based on a study of 127 depressed women contacting psychiatric services in North London and deals with the role of positive events in recovery. Each of the studies replicate a prior one and confirm the importance of considering specific meaning. The first study demonstrates that loss is important in provoking depression, danger for anxiety, and danger and loss for the onset of mixed depressive and anxiety disorders. The second study suggests that positive events involving hope are particularly important for recovery in depression. PMID- 8346334 TI - Pathological grief: diagnosis and explanation. AB - Pathological grief deserves a place in the diagnostic nomenclature. Because posttraumatic stress disorder requires an event beyond the range of usual experience and bereavement is virtually a universal experience, a new diagnosis of signs and symptoms precipitated by a loss event is needed. Many varieties of pathological grief have been noted in clinical research studies, and multiple diagnoses of pathological grief would make research difficult. The authors advance a solution in a personality-based explanation of abnormal responses to loss events; this allows for a single diagnosis of pathological grief. The authors also present a predictive model to partially explain pathological grief by antecedent trait combinations. The hypothesis is that persons with a preloss combination of both contradictions in relational schemas about the deceased and tendencies toward excessive control to stifle unwanted affect will tend to have unsuccessful processes of mourning. Types of contradictions and overcontrol may vary, yielding personality-based varieties of response within a single diagnostic category. PMID- 8346335 TI - Control and intrusive memories as possible determinants of chronic stress. AB - Amidst confusion about the nature and usefulness of the stress construct and distinctions between acute and chronic stress, research has begun to identify mechanisms by which stress affects health and by which stress can persist beyond the physical presence of the stressor. In addition, research has begun to identify reasons for selective vulnerability to chronic stress. One of the possible reasons for chronic stress following traumatic events is the disorganizing effect of loss of control and violation of expectations for regulating aspects of one's life normally under control. Data from a longitudinal study of chronic stress at Three Mile Island in the wake of the nuclear accident there suggest that loss of control and frequent experience of intrusive memories about the accident and its aftermath were related to persistent stress responding several years after the accident. The relationships between stress responding and conditioning and consolidation of stressful memories are considered as a basis for persistent intrusive memories and chronic stress. PMID- 8346336 TI - Long-lasting hormonal alterations to extreme stress in humans: normative or maladaptive? AB - The biological consequences of stress have been studied for over half a decade, however, little is known about persistent biological alterations after extreme stress in humans. Posttraumatic stress disorder (PTSD) is a syndrome that occurs in some individuals after exposure to extreme stress. In this review, we summarize some of our studies of hypothalamic-pituitary-adrenal axis alterations in PTSD and compare and contrast these findings with knowledge concerning biological changes following stress. PMID- 8346337 TI - Psychosocial factors and immunity in nonhuman primates: a review. AB - This review summarizes research from several laboratories that has assessed the influence of psychosocial factors on immune responses in nonhuman primates. These studies have demonstrated that the formation and disruption of social relationships should be viewed as significant psychobiological events with many immunologic sequelae, especially for the young monkey. Prolonged changes in leukocyte numbers, in vitro measures of lymphocyte function, and antibody responses to antigenic challenge have been reliably observed. There is also evidence in infant monkeys suggesting that normal maternal care may be important for the development and maintenance of the physiological set points for certain immune responses. Similarly, immune responses in adult monkeys can be affected by the level of aggression occurring within the group. Collectively, this research reiterates the important influence that psychosocial variables can have on basic physiological responses, particularly when social relationships are in the process of change. PMID- 8346338 TI - Ambulatory stress psychophysiology: the study of "compensatory and defensive counterforces" and conflict in a natural setting. AB - Thirty years ago, Donald Oken raised basic questions about psychophysiological research strategies for the study of the "psychological stress response" in the laboratory. Is it possible to simulate in the laboratory the situations one normally encounters? Do laboratory stimuli provoke affective arousal? Are different classes of stress stimuli associated with specific physiological response patterns? How do one's characteristic "defenses" and coping styles modulate one's responses? This paper describes a novel ambulatory research strategy in which the laboratory is moved into the natural setting. The advantages of this strategy are exemplified in studies of paramedics in whom 24 hour recordings were made of ambulatory blood pressure and heart rate. The ambulatory physiological data were then related to information about specific work location and subjective ratings of stress made in a diary at the time of each reading, objective assessments of the different stressful situations encountered, and the role of individual differences in anger expression and defensiveness in modulating these relationships. The findings illustrate the ability of real-life stressors to bring out relationships not typically obtained in the laboratory. Moreover, the natural setting permits individuals to respond to behavioral challenges using their preferred mode of coping with stress, as opposed to the constraints imposed on them in the laboratory. This research strategy has also helped uncover the significance of conflict about the expression of hostility, rather than hostility per se, as a key factor in the "stress response." PMID- 8346339 TI - [Prolegomena to nonionizing radiative energies. Their biological effects and the protection elements. I]. PMID- 8346340 TI - [The mammographic images of the irradiated breast after conservative therapy for carcinoma]. AB - The mammographic patterns of the patients treated with conservative surgery (quadrantectomy) plus radiotherapy for early breast carcinoma were evaluated to assess treatment-induced changes over time and to improve the differential diagnosis between postirradiation effects and possible tumor recurrences. The mammographic examinations of 79 patients who had undergone quadrantectomy and radiotherapy for breast carcinoma (stage T1-T2) were examined. Skin thickening, edema, fibrosis, distortion and calcifications were considered and classified by comparing the radiographic patterns of the treated breast with those of the contralateral and untreated one. Pattern changes over time were also evaluated and quantified by comparing serial follow-up examinations of the same breast. The percentage of patients with irradiation-induced skin thickening steadily reduced from 100% at 6 months to just above 50% at 4 years. The number of patients showing diffuse irradiation-induced edema decreased from 56% at 6 months to 15% at 1 year and to 0% at 2 years, while the number of cases with localized edema decreased more slowly. The incidence of localized postirradiation breast fibrosis increased to 74% at 4 years, while diffuse fibrosis stabilized around 14%. The patients with no postoperative breast distortion accounted for nearly 33% of the examined cases, while those with minimal distortion approximated 58% and those with gross distortion 9%. In conclusion, the overall results confirmed the value of mammography in the follow-up of the patients treated with QUART. PMID- 8346341 TI - [CT in the diagnosis and treatment of lymphoceles following gynecologic cancer surgery]. AB - The staging of gynecologic cancers requires the knowledge of lymph node status and thus pelvic and/or lumbo-aortic lymphadenectomy remains, to date, a widely used procedure. Lymphoceles are a frequent complication of surgical lymph node dissection. They are lymph collections in the retroperitoneum following the continuous drainage of afferent lymph vessels. To assess the incidence of this complication, its CT features and the role of diagnostic imaging to treat lymphoceles, 140 patients were retrospectively evaluated. Forty of them had undergone pelvic and/or lumbo-aortic lymphadenectomy for proved endometrial carcinoma, 51/140 for proved carcinoma of the cervix uteri, and 49/140 for proved malignant epithelial cancer in the ovary. CT exams were performed during the follow-up, not on a systematic basis but only when a recurrence was clinically suspected (117 cases), or in the presence of surgery and/or irradiation complications (11 cases), or to assess the extent of residual lesion during chemo/radiotherapy (12 cases). Fifty-three lymphoceles were observed in 36 patients: they were monolateral in 18 cases and bilateral in 16; in 34 cases the lymphoceles were found in the iliac space and in 3 cases only in the median perivascular lumbo-aortic space. In the patients with clinically suspected recurrence (117 patients, 27 lymphoceles), lymphoceles were associated with the recurrence in 25 cases, while they were the only CT evidence of a mass in 2 patients. In the cases with clinically suspected complications of former irradiation and surgery (11 patients, 3 lymphoceles), lymphoceles were correctly differentiated from abscesses (2 cases), seroceles (1 case), and hematomas (2 cases). In the group of asymptomatic patients monitored for residual disease (12 patients, 5 lymphoceles), lymphoceles were an occasional finding and, since they caused no complications to the urinary and GI tracts, they were never treated. Four asymptomatic patients only, with no evidence of disease, were submitted to transcutaneous aspiration and drainage under CT-US guidance (1.7 procedures per patient), and lymphoceles resolved in 3/4 cases. The only lymphocele recurring more than once required another laparotomy. In our experience, lymphoceles appear as a common sequela of pelvic lymphadenectomy for gynecologic cancer. CT has proved to be a useful diagnostic tool to assess and characterize the lesions, which must be differentiated from other postoperative complications and from recurring tumors. Lymphoceles needed to treatment in most cases and thus only symptomatic patients, with no cancer, were submitted to aspiration and drainage under CT-US guidance; the maneuver was successful on 75% of cases. PMID- 8346342 TI - [Xeroradiography and digital luminescence radiography in the study of the technics of manufacturing ancient ceramics. The advantages and limits]. AB - This paper reports on the cooperative work of the Department of Radiology of the Catholic University, Rome, and of the Italian Institute for Middle and Far East. The study was aimed at using xeroradiography and digital luminescence radiography for the archeometric evaluation of ancient ceramics and at assessing the imaging potentials of the two techniques. Some manufacturing techniques are reported which were used in the ancient world and societies for pottery making--i.e., coil building (the superimposition of clay rings), paddle and anvil beating and throwing of the wheel. Such techniques leave, on the vessel's wall, clear traces which can be detected by X-ray imaging. After discussing the main semiologic features, we present 4 case studies from the project archive. Each vase underwent xeroradiography and digital luminescence radiography. The former technique was useful in detailing minor phase transitions--e.g., pores and inclusions--while the latter, thanks to both its wide dynamic range and its image processing potentials, was optimal in defining very gradual thickness transitions due to the different techniques used to join the clay parts. By combining the two techniques, the manufacturing technology of the artifacts could be defined. The interactive processing of radiographic images at the system console was seen to be of major importance: it allowed the best results to be obtained thanks to the integration of the radiologists' and archeologists' know-how during the actual analytical stages. PMID- 8346343 TI - [A new biological irradiator for the laboratory]. AB - The use of high doses (15-20 Gy) of X- or gamma-rays to irradiate blood-derived materials is a common practice by now. It is usual especially when materials must be transfused into non-immunocompetent patients. This is done to avoid the so called GVH disease. Nowadays, for this purpose, units containing radioactive gamma-emitting sources with high activity and long half-life (usually 137Cs) are on the market. The characteristics of these "irradiators" allow their implementation in any laboratory with no need of structural shieldings. In spite of it, serious accidents (e.g., fire, fallings, etc.) which could imply hazards for the operating staff and even the general population, cannot be excluded. At the same time, the problem of long-term disposal of exhausted sources cannot be neglected. For these reasons, a new type of self-shielded irradiator was designed. It is equipped with an X-ray tube, operating at nearly 200-kV voltage, with 12-mA anodic current. The system is water- and oil-cooled and can work for a long time without thermal overloads. In this paper, the environmental and dosimetric measurements for beam characterization are reported. The system can produce beams with satisfactory characteristics for this specific problem. Moreover, its use may greatly reduce administrative radioprotection problems. PMID- 8346344 TI - [The prognostic role of the parameters of cellular kinetics in head and neck tumors treated solely by radiotherapy]. AB - Cell cycle and cell population characteristics, as obtained for head and neck cancers by flow-cytometry analysis of a single tumor sample, after in vivo bromodeoxyuridine (Burd) infusion, were proposed for their prognostic value and for their potentials for radiotherapy planning (conventional vs accelerated) and monitoring. DNA ploidy, the S phase fraction labeling index (LI), and duration (Ts) as well as cell population potential doubling time (Tpot) were measured in 42 head and neck squamous cell carcinoma patients and analyzed along with histopathological and clinical data. Twenty-seven patients received standard radiotherapy (70 Gy/35 fractions/7 weeks) whereas 15 patients were treated with the concomitant boost technique (75 Gy/40 fr/6 weeks). The univariate analysis of 31 patients, for whom all the cell kinetic parameters were available, indicated that local control probability was strongly affected by lymph node status (p = 0.05) and by potential doubling time (p = 0.04). Patients having tumor Tpot < 5 days had markedly lower two-year local control rate (13%) than patients with Tpot > 5 days (68%). Furthermore, tumors with Tpot < or = 5 days exhibited a trend toward better local control after concomitant boost regimen compared with the patients treated with standard regimen (p = 0.06). These preliminary results point out that Tpot could play a role as additional prognostic factor influencing disease outcome in head and neck carcinomas treated by radiotherapy. In patients with fast growth-rate tumors (Tpot < or = 5 days) a more aggressive radiotherapy combination or chemo-radiotherapy should be suggested. PMID- 8346346 TI - [An intracranial arachnoid cyst with a repeated intracystic hemorrhagic complication]. PMID- 8346345 TI - [Anatomico-functional assessment by neuroimaging technics in a female patient with partial posttraumatic epilepsy]. PMID- 8346347 TI - [Altered ventilation of the right lung due to tubercular adenopathy treated by endoscopic laser surgery]. PMID- 8346348 TI - [The traumatic opening of a mediastinal bronchogenic cyst in the left primary bronchus]. PMID- 8346349 TI - [A case of leiomyoma of the breast]. PMID- 8346350 TI - [Bilateral galactoceles in an 18-month-old male infant]. PMID- 8346351 TI - [CT in tumors of the horseshoe kidney. A report of 2 cases of adenocarcinoma]. PMID- 8346352 TI - [Integrated imaging of the vessels of the neck]. PMID- 8346353 TI - [Ovarian carcinoma and intrasplenic metastases. A report of 4 cases]. PMID- 8346354 TI - [The echographic diagnosis of a sigmoid-bladder fistula. A case report]. PMID- 8346355 TI - [The quantitative assessment of pulmonary emphysema by computed tomography. The evolution of the methods and their possible applications]. PMID- 8346356 TI - [The radiological diagnosis of bronchiectasis today]. PMID- 8346357 TI - [The assessment of the severity of pulmonary edema by computed tomography. A comparison between high-resolution computed tomography, objective evaluation with density masks and functional tests]. AB - The results of high-resolution computed tomography (HRCT) were correlated with those of pulmonary function tests, chest films and CT expiratory density mask values in the evaluation of pulmonary emphysema in 33 symptomatic subjects. Emphysema was quantitated with both subjective and objective measurements. Conventional chest films were useful to diagnose severe emphysema but its actual extent was more reliably evaluated with CT scoring systems. HRCT and density mask correlated well with function tests, but the former method exhibited stronger correlation with carbon monoxide diffusion capacity. The opposite was true for hyperinflation and expiratory obstruction variables. Subjective CT estimates, which are quick and easy to perform, were seen to correspond more specifically to the pathophysiologic derangement and should therefore be used to evaluate the anatomic extent of disease. The functional severity of emphysema correlated only with the overall extent of disease and not with its regional distribution in the upper or lower lungs. Finally, in 4 cases (12.1%) with low CT scores, FEV1 was reduced but diffusion capacity values were normal. In one of these patients HRCT showed signs of bronchiolitis. In fact, small airway disease might be a more critical factor in determining functional impairment than the actual anatomical emphysema. PMID- 8346358 TI - [The diagnosis of lung inflammation in AIDS patients. The use of 99mTc-labelled human polyclonal immunoglobulins and a comparison with 67Ga citrate and high resolution computed tomography]. AB - Technetium-99m (99mTc) labelled polyclonal human immunoglobulin (HIG) is a new agent for the localization of active inflammatory diseases. The results obtained with HIG in 29 AIDS patients referred for suspected lung infections are reported (Table I). The patients also underwent Gallium-67 citrate scanning (GS), chest radiography (Rx), high-resolution thin-layer computed tomography (HRCT) and broncho-alveolar lavage (BAL). The study population was classified as follows: 12 patients (Table II) were studied before treatment for suspected Pneumocystis carinii pneumonia (PCP), 7 patients (Table III) had known PCP and were studied during medical therapy, and 10 patients (Table IV) had lung infections other than PCP. In all PCP patients studied before treatment, positive agreement was observed between HIG, Rx and HRCT findings. In 4 patients with final clinical diagnosis of no lung conditions, both nuclear and radiologic imaging were negative. 99mTc-HIG results in the PCP patients studied during therapy were consistent with clinical and radiologic improvement; there was disagreement with 67Ga findings in one case (no. 9). In lung infections other than PCP, HIG studies were often negative (always negative in mycobacteriosis), while they were positive in 3 pyogenic abscesses. In conclusion, as for PCP and abscesses, the results obtained with 99mTc-HIG are usually in agreement with GS findings, while HIG scans seem to be negative in mycobacterial infections. Moreover, HIG scintigraphy seems to be suitable for the evaluation of treatment results in PCP (this subject deserves further research). To assess respiratory impairment a semiquantitative index (ISQ) of 99mTc-HIG lung uptake is suggested, which showed a significant linear correlation with arterial pO2. PMID- 8346359 TI - [Echography, magnetic resonance and double-contrast arthrography of the rotator cuff. A prospective study in 30 patients]. AB - Shoulder pain is a common clinical problem with different etiologies. Without a specific diagnosis, treatment could be ineffective, causing functional limitation, chronic pain and atrophy. US and MRI allow in many cases to correctly define the different etiologies causing shoulder pain, often due to rotator cuff conditions. From June to September 1992, thirty patients with clinically suspected acute or chronic rotator cuff lesion were studied with US, MRI and double contrast arthrography. US and MRI findings were evaluated and compared using arthrography and surgery as the gold standard. The overall accuracy of MRI was 93%: the method yielded accurate information about size and number of rotator cuff tears, and about bursal, bone and muscle involvement. US accuracy was 83% in the diagnosis of large tears, 63% in the diagnosis of small and partial tears and only 11% in the diagnosis of tendinitis. Both MRI and arthrography exhibited high accuracy (respectively 91 and 100%) in the detection of rotator cuff tears when their results were compared with surgical findings. A flow chart to be used in the patients with acute or chronic shoulder pain was drawn from the critical analysis of the above results. PMID- 8346360 TI - [Reconstruction of the anterior cruciate ligament using the patellar tendon: its magnetic resonance evaluation]. AB - MRI of the knee was performed in 30 patients who had been submitted to arthroscopically-guided reconstruction of the anterior cruciate ligament from patellar tendon. The autograft structure was investigated and MR results were correlated with clinical findings. Partial/total meniscectomy had been carried out in 21/30 cases. The patients were imaged at various postoperative intervals (3-24 months) by means of an 0.5-T magnet (GE MR Max Plus) in full knee extension and internal rotation. Sagittal and axial T1-weighted images (slice thickness: 3 mm) were combined with real-time reconstruction which better demonstrated the whole graft. T2-weighted coronal images (slice thickness: 5 mm) were also acquired. In each patient the following clinical variables were considered: anterior drawer sign, Lachman test, pivot shift, degree of leg extension, and finally functional recovery. The following MR variables were then considered: structure and alignment of bone tunnels, structure and signal intensity of the graft, degree of synovial inflammation, structure and signal intensity of the posterior cruciate ligament and finally structure of the menisci and/or meniscal residues. Symptoms-MR correlation suggests that the different outcome of surgical reconstruction may depend on the correct alignment of the tibial and femoral bone tunnels and on good meniscal condition. Bone tunnels must be located on the same plane, posterior and parallel to the slope of the intercondylar roof, since angulation causes the latter to impact the graft during knee extension, with inflammation and risk for rupture. As for menisci, tiny residues or total ablation overload tha graft, whose signal increases and whose synovia becomes inflamed. The latter pattern is always distinguished from that of the autograft, whose signal intensity seems not to change in time. In conclusion, MR proved an accurate and non-invasive technique to image this kind of postoperative knee, since metallic artifacts do not reach the joint space. PMID- 8346362 TI - Hazards from pathogenic microorganisms in land-disposed sewage sludge. AB - Sewage sludge is a complex mixture of organic and inorganic compounds of biological and mineral origin that are precipitated from wastewater and sewage during primary, secondary, and tertiary sewage treatment. Present in these sludges are significant numbers of microorganisms that include viral, bacterial, protozoan, fungal, and helminth pathogens. The treatment of sludge to reduce biochemical oxygen demand, solids content, and odor is not always effective in reducing numbers of pathogens. This becomes a public health concern because the infectious dose for some of these pathogens may be as low as 1 particle (virus) to 50 organisms (Giardia). When sludge is applied to land for agricultural use and landfill compost, these pathogens can survive from days (bacteria) to months (viruses) to years (helminth eggs), depending on environmental conditions. Shallow aquifers can become contaminated with pathogens from sludge and, depending on groundwater flow, these organisms may travel significant distances from the disposal site. Communities that rely on groundwater for domestic use can become exposed to these pathogens, leading to a potential disease outbreak. Currently, methods to determine the risk of disease from pathogens in land disposed sludge are inadequate because the sensitivity of pathogen detection is poor. The application of recombinant DNA technology (gene probes and polymerase chain reaction) to environmental samples may provide increased sensitivity for detecting specific pathogens in land-disposed sludge and greatly improved risk assessment models for our exposure to these sources of pathogens. PMID- 8346361 TI - [Definition of the T parameter in nasosinusal neoplasms: a CT-MR comparison]. AB - This study was aimed at investigating the value of CT and MRI in the staging of sinonasal tumors. The authors report 22 cases of sinonasal tumors: 7 squamous cell carcinomas, 4 adenoid-cystic carcinomas, 1 mucoepidermoid carcinoma, 6 adenocarcinomas, 1 esthesioneuroblastoma, 1 osteosarcoma, 1 small-cell sarcoma and finally 1 non-Hodgkin lymphoma. No significant differences were observed between CT and MR staging: 2 T2 and 15 T4 lesions were diagnosed in the maxillary sinuses and 3 stage-II and 1 stage-III lesions in the naso-ethmoidal region. Tumor spread was similar in 20/22 cases: MRI excluded the involvement of maxillary and sphenoid sinuses in 2 cases. CT was superior in the assessment of bone destruction particularly at the base of the skull, but MRI better demonstrated intracranial spread. MRI detailed the intraorbital muscles and, in the infratemporal fossa, the pterygoid muscles better than CT. High agreement was observed between CT and histology in 5/7 cases and between MRI and histology in 6/7 cases undergoing craniofacial resection. Seventeen of 22 cases had low to intermediate signal intensity on T1-weighted, PD and T2-weighted MR images. Signal was hyperintense in 5 cases: 1 adenocarcinoma with mucinous features, 3 adenoid-cystic carcinomas and 1 esthesioneuroblastoma. In agreement with literature data, this study confirms CT as the examination of choice in staging sinonasal tumors: nonetheless, MRI yields valuable information in the cases with tumor spread to the muscles and soft tissues. PMID- 8346363 TI - [Pollution in the home interior and asthma]. PMID- 8346364 TI - [The pertinence of bronchial provocation tests to allergens]. AB - The contribution and the relevance of bronchial provocation tests to allergens have been evaluated in the realm of clinical research and in the diagnosis of the aetiology of asthma. These tests enable the recognition or to confirm the role of certain allergens in asthma, as well as to study the delayed reaction which occurs in some cases after the inhalation of an allergen as well as the relations existing between HRBNS and bronchial provocation tests to allergens. They also can show the preventative action of certain drugs on the immediate and/or delayed reaction induced by allergens. The methodology of bronchial provocation tests to allergens, notably their variability and their reproductibility, as well as the initial and maximal inhaled doses that can be realistically used, are discussed. The final point touched upon concerns the justification of bronchial provocation tests to allergens in the aetiological diagnosis of asthma. The indications of these tests have been restricted, they seen nonetheless always to be of interest in cases of discordance with the clinical history, cutaneous tests and/or measures of specific serum IgE. PMID- 8346365 TI - [Healing of bronchial anastomoses in single and double pulmonary transplantations]. AB - Bilateral single lung transplantation (BSLT) (the procedure of choice for double lung replacement) and single lung transplantation (SLT) have at present a low incidence of anastomotic problems. In our experience, we have recorded no death related to anastomotic problems and 4 complications occurred for 33 anastomoses with a follow up of at least 2 months. A stent was temporarily inserted for two patients. The decrease of anastomotic complications is confirmed in the literature. It is one of the reasons why the number of SLT and BSLT performed all over the world increases rapidily to the detriment of heart lung transplantation. PMID- 8346366 TI - [Severe late stage lesions of pulmonary histiocytosis X. Report of 3 transplantations]. AB - The anatomical lesions of three subjects suffering from pulmonary histiocytosis X and treated with lung transplantation were studied in order to detail the changes occurring in late stages of the disease; the early stages are known on account of lung biopsies done with a diagnostic aim. All the subjects were, at the time of transplantation, in a precarious clinical state and were practically bed-bound as a result of their dyspnoea with a history of histiocytosis X which had been known for 9, 7 and 3 years respectively; one patient had a cardiopulmonary bypass and two unilateral lung transplant. The results of the histological study produced data which was slightly discordant from the communly held ideas; the de Langerhans cells persist in large numbers and after many years of the evolution of the disease, even though other elements of the granuloma have practically disappeared. Fibrosis is absent playing no role in the genesis of the respiratory failure. The lesions are destructive, leading to a disappearance of the alveolar capillary bed which is the source of the dyspnea. The honeycomb cavities to the destroyed lung are varied in nature: most correspond to the disappearance of the dividing walls of the alveoli or the pulmonary acinus, some others related to dilated terminal bronchioles and finally others to hollowed out granulomas which have become cavities. The peculiar characteristic of the lung allows for destructive cavities to be produced by the airflow, submitted to a process of auto-aggravation by the elastic forces and the tension of the pulmonary parenchyma. PMID- 8346367 TI - [Asthma, urban atmospheric pollution and the weather]. AB - The aim of this study, which was carried out in an urban environment, was to research in to a possible relationship between temporal variations in the level of atmospheric pollution in the centre of Paris, compared to the frequency of acute dyspnoeic crises in which asthmatic patients had requested the emergency service (SOS Medecins). This study began in the first half of 1989; during this period there were 701 cases of acute asthma recorded within the Paris city boundary by "SOS Medecins". The pollutants recorded were sulphur dioxide (SO2), an index of black smoke (FN), oxides of nitrogen (NOx), ozone (O3) and soluble sulphate particles (SO4). In addition, the weather patterns were examined and pollen counts were recorded. In spite of a sub-acute episode of pollution in January and February, there was no definite increase noted in the number of emergency calls made for acute asthma. In the first three months, the number of crises were, on average, higher in association with high levels of the principal pollutants (SO2 FN, NOx, SO4) as well as with the periods of high atmospheric pressure; however, only the sulphate content and atmospheric pressure remained correlated with the daily number of asthmatic crises. In the second three months, there were some co-variations uniquely associated with sulphate particles, the atmospheric pressure, and above all the ozone level (allowing for a gap of one day). The influence of the daily variations in total pollen content or of grass pollens did not show up in this study. PMID- 8346368 TI - [Urban asthma and habitat]. AB - This study examines in urban area the housing conditions in asthma patients who called a first-aid association of doctors (SOS Medecins) and their relationships to symptoms. The patient population is compared with the non asthmatic population who called SOS Medecins during the same period. During the first six months of 1989, among 102,791 calls, 701 were related to acute asthma symptoms, and 100 non asthma patients were sorted at random as a control group. A telephonic questionnary has been carried out to asthmatic patients and to control group. A particular aspect of asthma in Paris is given in this study: the homogeneous distribution of asthma attacks in the different districts of Paris, (with a light prevalence in three districts of the city). Sex, age, occupation were non discriminant and no significant difference was established in housing conditions and indoor air pollution sources, between the two groups of asthma and non-asthma patients. PMID- 8346369 TI - [Surgery for bronchiectasis. Operative indications and results. 48 observations]. AB - Forty-eight patients: 27 women and 21 men, with mean age of 36 +/- 14 years were operated on for bronchiectasis from 1976 to 1989. In 20 cases bronchiectasis was the sequelae of acute bronchopathy of childhood, 6 cases of tuberculosis and 5 cases of inhalated foreign bodies. The bronchiectasis was apparently primitive in 12 occasions. Five varied etiologies were found of which 2 congenital hypogammaglobulinemias. The anatomic extension of the lesions was precised in 47 cases by bronchography and CT scan in 6 cases, in 1 case with CT scan only. The lesions were bilateral in 5 cases. One pneumonectomy, 42 lobectomies (of which 10 bilobectomies) and 5 segmentectomies were performed. The operative mortality was nil. The morbidity (14 cases among 48, i.e. 29%) was not negligible and was comparable with the literature data. The evalued results for 36 patients (mean post-operative follow-up: 54 +/- 58 months) showed that 24 patients (67%) were asymptomatic, 34 have taken their normal professional activities. PMID- 8346370 TI - [Chronic atrophic polychondritis. Clinical polymorphism and severity of respiratory lesions]. AB - The authors report the case of chronic destructive polychondritis (PCA) with extensive and predominant laryngo-tracheal involvement. The respiratory localisation of PCA is apparent in around 50% of cases. In a quarter of patients presenting with this type of localisation, the outcome is fatal. Tracheal disorders as the presenting feature is a rarity, as in the majority of cases it occurs either concomitantly or after the appearance of classic cartilagenous disease in the nose or ear. The diagnosis of the airways disease rests on the interpretation of the flow volume curve and the CT scan of the inspiration and expiration. Taking account of the absence of any correlation between the disturbed respiratory function and the laryngotracheal bronchial lesions, the authors stress the value of an endoscopic assessment with a fibroscope of reduced calibre. The narrowing of the laryngo-tracheal region is due to a thickening of the walls with oedema and inflammatory granulomas, and to collapse of the lumen caused by the destruction of cartilage and by fibrous scarring of the tracheal walls. Either general or local treatment is virtually non-existent and the prognosis of these extensive respiratory forms of the disease is very poor. PMID- 8346371 TI - [An uncommon thoracic tumor: an hour-glass shaped parietal lipoma. Contribution of MRI and CT]. AB - One case of transmural thoracic lipoma is reported. Thoracic lipomas are rare tumors. This report illustrates the usefulness of CT and MRI in the preoperative diagnosis and subsequent evaluation of transmural thoracic lipoma. PMID- 8346372 TI - [Multiple complications of a mycoplasma pneumoniae infection]. AB - We report the case of a patient who was admitted to hospital for a pneumonia in association with a Stevens-Johnson syndrome. The association of these conditions suggested a Mycoplasma pneumoniae infection, which was confirmed on serology. There were three other extra-respiratory complications discovered: cold agglutinins, a disturbance of liver function tests, and circulating anticoagulant; both the two latter and the Stevens-Johnson syndrome are rare complications. PMID- 8346373 TI - [Pulmonary and cerebral nocardiosis in a patient infected with HIV]. AB - We report a case of pulmonary and cerebral nocardiosis in a patient infected with HIV. On the basis of this observation, the authors review the frequency of nocardiosis during the course of an HIV infection and the diagnostic problems proposed, and finally the therapeutic difficulties encountered. PMID- 8346374 TI - [Atypical pulmonary hydatid cyst]. AB - An atypical form of a pulmonary hydatid cyst is described. This was a solitary super-infected pseudo-tumoral cyst and the membrane was incarcerated which has enabled us to propose as a description for this new morphological aspect of a cyst, with a filled margin of the proliferative membrane. We propose the term "Rosebud". PMID- 8346375 TI - [Acute bronchospasm due to periwinkle alkaloid and mitomycin association]. AB - We report six cases in which patients presented with acute dyspnoea following injections of either vindesine or vinorelbin. These patients were receiving chemotherapy in association with cisplatin, mitomycin, and vindesine or vinorelbin, for inoperable bronchial cancer. Three of the patients had evidence of airflow obstruction before these incidents. The clinical picture suggested bronchospasm and appeared in the two hours following an injection of the vinca alkaloid and a significant time away from the administration of the mitomycin. Additional respiratory support was necessary in one patient, the bronchial spasm stopped spontaneously in three cases, and following bronchodilator in two. The respiratory toxicity of vinca alkaloids (vindesine, vinblastin) was observed in 4% of the cases, uniquely when they were associated with mitomycin. Vinorelbin seems to possess the same respiratory toxicity. The bronchospasm, sometimes very severe, seems to occur in the two hours following the injection in the case of the cytotoxics and some time after the administration of mitomycin. The recurrence of the bronchospasm is a constant feature when the vinca alkaloid is readministered. This side effect is different to the pulmonary fibrosis due to mitomycin. Clinical follow up and spirometry is thus necessary in those patients receiving chemotherapy in which vinca alkaloids and mitomycin are associated and the regime should be followed after each administration of a vinca derivative. After the first episode of dyspnoea, it is probably wise to stop the administration of these anti-mitotics to prevent any further respiratory side effects which could be more severe. PMID- 8346376 TI - [Subpleural adenopathy]. PMID- 8346377 TI - [Mediastinal pseudo-tumor: 2 case reports]. PMID- 8346378 TI - [2000 asthma deaths in France each year: who are they?]. PMID- 8346379 TI - [Anti-tuberculous program in the Long-An province (South Vietnam). 5 year prospective study]. PMID- 8346380 TI - [What is your diagnosis? Reactive salmonella oligo-arthritis with bilateral involvement of the proximal ankle joint]. PMID- 8346381 TI - [Magnesium therapy of acute heart infarct--has its time come?]. PMID- 8346382 TI - [Is there a clinical indication for the determination of atrial natriuretic peptide?]. AB - Atrial natriuretic peptide (ANP) is a hormone produced, stored and secreted by atrial muscle cells. By its natriuretic, diuretic and blood pressure lowering activities ANP is possibly an endogenic antagonist for the sodium-retaining, vasopressor renin-angiotensin-aldosterone system (RAAS). In diseases associated with increased intravascular volume ANP plasma concentrations have been found elevated, in those associated with decreased volume ANP has been found decreased. In essential hypertension and chronic heart or renal failure diagnostic conclusions may be drawn from the ANP plasma concentration. This review summarizes the present knowledge about physiology and pathophysiology of ANP and values in addition the diagnostic power of ANP measurements for clinical routine in hypertension, heart and renal failure. PMID- 8346383 TI - [Tremors]. AB - Tremor can present a diagnostic problem in family practise. Systematic analysis of this symptom allows rapid classification of the problem without use of rigid definitions. Unilateral or very asymmetric tremor that disappears at the onset of a movement is for example a typical sign for parkinsonism without analysis and differentiation between tremor at rest or position-dependent tremor. Also one may assume, that a symmetric tremor that aggravates during standing or movement in most cases is essential and not of cerebellar origin. Different forms of tremor and their therapies and main tremor types are presented graphically. PMID- 8346384 TI - [Febrile status and micronodular changes of the lung parenchyma in HIV infection]. AB - This 49-year-old man with the acquired immunodeficiency syndrome (AIDS) was admitted to the hospital because of fever, weight loss and respiratory symptoms. The radiograph of the chest showed diffuse fine nodular opacities. Histology of lung and lymph node revealed a necrotising granulomatosis and yeasts suggesting histoplasmosis. It's identity was confirmed by positive cultures for Histoplasma capsulatum in blood, urine, lung specimen and lymph node. There was a successful induction treatment and a maintenance therapy with amphotericin B. We discuss disseminated histoplasmosis in the immunodeficiency syndrome. PMID- 8346385 TI - [A case from practice (271). Therapy-resistant leg ulcer of venous origin due to calcifications in the subcutaneous ulcer area]. PMID- 8346386 TI - [Vaccine against AIDS is being tested]. PMID- 8346387 TI - [Eating behavior. Contributions from anthropology]. PMID- 8346388 TI - [Anthropology and drug dependence]. PMID- 8346389 TI - [The medicalization of sex]. PMID- 8346391 TI - [Professional nursing]. PMID- 8346390 TI - [The anthropology of death]. PMID- 8346392 TI - [Anthropology and education for health]. PMID- 8346393 TI - [The use of anthropology for tackling care situations]. PMID- 8346394 TI - [The reorientation of the nursing activities in health centers]. PMID- 8346395 TI - [Continuing education. 81. Medical-surgical. Acute kidney failure]. PMID- 8346396 TI - [An anthropological "look" at health and disease]. PMID- 8346397 TI - [Epidemiological trends of primary lung cancers]. AB - Due to a dramatic increase in the present century, lung cancer is now undoubtedly the most frequent cancer in the world. Their principal risk factor for lung cancer is active smoking, but passive smoking is also responsible. Eighty to 90% of lung cancer cases in men and 50 to 75% in women are caused by tobacco smoke. The most effective prevention is cessation of smoking. PMID- 8346398 TI - [Mechanisms of lung oncogenesis]. AB - Precancerous lesions of the bronchial epithelium are dysplasias and in situ carcinomas. Squamous metaplasia has not yet been considered as a true malignant state. Epithelial cells, which are able to proliferate (non terminally differentiated) in bronchial tree and alveoli, are the candidates for malignant proliferation (basal cells, mucus cells, Clara cells and type II pneumonocytes). Their initial growth is probably promoted by deregulated autocrine growth factors (EGF, GRP, IGF1), or their receptors (EGF-R). Under continuous carcinogens exposition these proliferating cells accumulate multiple genetic abnormalities affecting dominant oncogenes such as myc and ras, and recessive tumor suppressor genes such as Rb and p53. Neither the order of intervention of these genetic factors nor their correlation with premalignant states have been demonstrated. PMID- 8346399 TI - [Anatomopathology of lung carcinoma: classic data and new concepts]. AB - The classification of lung cancers is based on that defined by the WHO in 1982. Electron microscopy and immunohistochemistry have put some tumours (carcinoids and small cell carcinomas) in the same neuroendocrine differentiation family. Between the two ends of the differentiation spectrum are tumours of intermediate malignancy, such as well-differentiated neuroendocrine carcinomas or atypical carcinoids. Numerous proposals of classification have been published, and in particular some large cell lung cancers have been included in the neuroendocrine carcinoma group. The type of lung cancer is sometimes difficult to diagnose on biopsy material; it is easier to determine with precision on surgical specimens. TNM evaluation is based on detailed macroscopic evaluation of local and regional lymph node invasion by the tumour. PMID- 8346400 TI - [Diagnosis of primary lung cancers]. AB - Symptoms of bronchial cancers are varied and misleading, source of late diagnosis which had to be avoided by systematic suspicion in front of all symptoms from a "high-smoker". Fiberoptic bronchoscopy is the best exam for anatomic diagnosis of central forms. It is normal in peripheral forms but may yet be useful by directed samplings. If negative, it may be necessary to perform thoracotomy or transthoracic needle punction if surgery is contra-indicated. Pretherapeutic assessment of loco-regional and metastatic extension has recently profited by new imaging and endoscopic techniques, useful to the best realisation of TNM classification. PMID- 8346401 TI - [Tomodensitometry imaging and MRI of primary lung cancers]. AB - Accurate determination of the extent of lung cancer is essential to decide on its surgical treatment and to evaluate its prognosis. Modern medical imaging is there to spare the patients an unnecessary thoracotomy, knowing that the only satisfactory treatment is surgical resection. Computed tomography (CT) and magnetic resonance imaging (MRI) are part of the preoperative evaluation, side by side with the patient's general condition, his cardiovascular and respiratory status and the histological type of his tumor. It seems rational to ask for these imaging methods for all tumors seemed to be operable after radiology and fibroscopy, except perhaps, for some authors, in cases of peripheral T1 NO tumors not in contact with the chest wall. CT remains the reference examination for preoperative evaluation of lung cancer extension, provided it is performed with technical rigor and is interpreted on the basis of strict criteria. The opposition of MRI in this field has not yet been definitely established, largely because of possible improvements of this new method in the years to come. In certain cases, it seems to be a useful complement to CT or even a possible alternative to this examination. PMID- 8346402 TI - [Effects of antibiotics of subinhibitory concentrations. New mechanisms of action for new indications]. PMID- 8346403 TI - [Mitochondrial diseases]. AB - Mitochondrial diseases are very complex. Their description, recent but still in progress, makes all classifications risky. In the first part of this article we present the original character of mitochondria, which is due to their functional structure aimed to produce energy, the respiratory chain being fundamental for the phosphorylation/oxidation and ATP production processes. Beside Mendelian transmission, mitochondria have their own DNA which codes for proteins that are few but play an essential role; the nuclear DNA probably has a regulatory effect. For these reasons, explorations of mitochondrial functioning, mainly by morphological, biochemical and genetic techniques, are specific. In the second, clinical part, we analyse the whole range of symptoms and syndromes which includes purely muscular lesions, predominantly nervous lesions and multisystemic lesions. Some syndromes can be individualized on a biochemical basis, whereas other are individualized on a genetic basis involving mainly mutations of mitochondrial DNA. Finally, we merely list lesions the origin of which might be mitochondrial but remains unknown. PMID- 8346404 TI - [Bacterial cutaneous infections: erysipelas. Etiology, diagnosis, clinical course amd treatment]. PMID- 8346405 TI - [Polyuria-polydipsia syndrome. Diagnostic orientation]. PMID- 8346406 TI - [Manic-depressive disease. Diagnosis, course, treatment]. PMID- 8346407 TI - [Renal colic. Diagnostic orientation and emergency treatment]. PMID- 8346408 TI - [Painful knee. Diagnostic orientation]. PMID- 8346409 TI - [Menopause. Diagnosis, treatment]. PMID- 8346410 TI - The specificity of alternative complement pathway-mediated lysis of erythrocytes: a survey of complement and target cells from 25 species. AB - Sera from 20 species of mammals were tested for their ability to lyse erythrocytes from 18 species of mammals and birds by the alternative complement pathway. Erythrocytes were not lysed by homologous complement, with one minor exception, but all erythrocytes tested were lysed by at least one complement source, and all sera tested except that of the horse lysed at least one type of erythrocyte. Control experiments indicated that lysis was via the alternative complement pathway and that antibodies were not involved. Complement from the various species could be ranked from most active to least active, and erythrocytes could be ranked from most susceptible to least susceptible. There was an inverse correlation between complement activity and erythrocyte susceptibility. The ranking of the orders of placental mammals, from strongest to weakest complement, was carnivore > artiodactyl (ruminants and swine) > primate = armadillo > rodent > rabbit > horse. Opossum serum had activity that placed it in the centre of this range. Ferret complement, the most potent tested, lysed all erythrocytes tested except for homologous erythrocytes, with APCH50 titres as high as 4000. Although the overall reactivity pattern was clear, there were several striking exceptions. For example, the only complement source which lysed ferret erythrocytes was sera of the mouse. The amount of sialic acid present on erythrocytes of 14 mammals was determined, and was, in general, directly correlated with resistance to alternative complement pathway lysis, although there were prominent exceptions to this correlation, involving erythrocytes of the horse, burro and human. All 20 types of complement were also tested for their ability to lyse antibody-coated human tumour cells, under conditions in which both the classical and alternative complement pathways were functional. The data obtained suggest that alternative pathway activation is, in some cases, a major factor determining the effectiveness of a particular complement source in the lysis of xenogeneic tumour cells. PMID- 8346411 TI - In vivo depletion of chicken T-cell subsets. AB - In the chicken three types of T-cell receptors can be defined by monoclonal antibodies TCR1, TCR2 and TCR3, which recognize gamma delta T cells, and V beta 1 and V beta 2-expressing alpha beta T cells, respectively. In the present report we have analysed means of selectively depleting the gamma delta T cells and the V beta 1+ alpha beta T cells. gamma delta T cells, which represent up to 66% of all T cells in blood of a 6-month-old chicken, can be effectively depleted by neonatal thymectomy (Tx) to levels as low as 1%. Immunohistology demonstrates a similar depletion in lymphoid organs while intestinal epithelium-associated gamma delta T cells are affected by Tx to a lesser extent. V beta 1-bearing alpha beta T cells, which comprise about 80% of the alpha beta T cells, were depleted by embryonic and neonatal injection of the TCR2 antibody. In the thymus such treatment depleted only the V beta 1+ alpha beta T cells with high density expression of T-cell receptor. Therefore, we thymectomized TCR2-treated animals in order to prevent development of mature V beta 1+ alpha beta T cells from the low density immature thymocytes. Treatment of chickens with a total of 22 mg of TCR2 antibody plus Tx reduced V beta 1+ alpha beta T cells from an average of 65% to 10% of all T cells. In these TCR2 antibody-treated animals the V beta 2 expressing alpha beta T cells become the predominant type of T cell (average 85%). PMID- 8346412 TI - Murine APC activation in the xenogeneic MLC. AB - Purified human T cells proliferate in response to direct and indirect presentation of human alloantigens. However, until recently it was believed that human T cells could respond only indirectly to murine xenoantigens. We recently used the mixed leucocyte culture (MLC) to demonstrate that purified human T cells proliferate in response to direct presentation of murine xenoantigens by murine antigen-presenting cells (APC) in the presence of human cytokines. We suggested that cytokines might function poorly across species barriers. In this study, we demonstrate that although proliferation occurs in the presence of exogenously added cytokines, the precursor frequency of responding human T cells is much lower in a xenogeneic than in an allogeneic MLC. We demonstrate that human T cells also proliferate in response to murine APC in the presence of murine cytokines, and murine cytokines augment the proliferative response seen in a human anti-human MLC, ruling out the possibility that an absolute cytokine incompatibility exists between these species. We show that exogenously added human IL-1 causes maximal proliferation of human T cells in response to murine xenoantigens only when added early in the culture. We further demonstrate that murine APC preincubated in human rIL-1, and washed extensively, prior to use as stimulating cells, cause human T-cell proliferation without the need for exogenously added cytokines. Finally, we noted that during interactions of human T cells and murine APC, little to no IL-1 is produced, whereas after the addition of exogenous IL-1, a marked increase in the production of IL-1 is seen. These data suggest that during interactions between human T cells and murine APC, the murine cells do not receive adequate stimulation to produce sufficient costimulatory signals to allow proliferation of the human T cells. PMID- 8346413 TI - Interleukin-6 is a mediator of TNF-alpha regulation of LAK cell function. AB - TNF-alpha at 50-100 U/ml synergizes with IL-2 in enhancing LAK activity and IL-6 production in low-dose IL-2 (1-10 U/ml) culture of human PBL. High-dose TNF-alpha (> or = 200 U/ml) has less effect and even sometimes resulted in lowering of both LAK activity and IL-6 production below control levels. TNF-alpha-mediated regulation of low-dose IL-2 activation occurs even at late stages (effector phase) of LAK development. IL-6, as previously reported, acts at late stages of low-dose IL-2 culture to enhance LAK, but does not stimulate TNF-alpha production. The combined addition of TNF-alpha and IL-6 to late stages of IL-2 culture does not produce any additive or synergistic effect on LAK. We tested for the relative roles of TNF-alpha and IL-6 in late stage regulation of LAK development with antibodies (Abs) to these cytokines. Anti-IL-6 Ab abrogates late phase LAK enhancement by TNF-alpha, while anti-TNF-alpha Ab has no effect on IL-6 augmentation of LAK cytotoxicity. IL-2 added to PBL culture at doses greater than 10 U/ml induces production of both TNF-alpha and IL-6. Addition of anti-TNF-alpha Ab at late stages of high-dose IL-2 (> or = 20 U/ml) culture decreases both LAK cytotoxicity and IL-6 production, and the inhibition of LAK is reversed by the addition of IL-6. By contrast, anti-IL-6 Ab decreases LAK cytotoxicity, but does not alter TNF-alpha production, and the inhibition of LAK is not reversed by addition of TNF-alpha. These data indicate that TNF-alpha is important for both LAK development and IL-6 secretion in PBL, and that IL-6 is the proximate mediator in TNF-alpha regulation of these cytotoxic cell functions. PMID- 8346414 TI - Development of B cells secreting endogenous or transgene-encoded immunoglobulins in H-chain transgenic mice. AB - The development of splenic B cells secreting transgene-encoded or endogenous immunoglobulin (Ig) was analysed in the mu heavy (H-)chain transgenic mouse line M54. The results show that cells secreting endogenous Ig are not detectable during the perinatal period, even after lipopolysaccharide stimulation in vitro. At this time, transgene-secreting cells are readily detectable and keep increasing with age of the animals. After a few weeks of age cells secreting endogenous Ig appear in the spleen and keep increasing with age, reaching numbers comparable to non-transgenic littermates by 5 weeks of age. Thereafter, the proportion of transgene-secreting B cells decreases. We conclude that the preferential expression of endogenous Igs by secreting B cells in the adult does not result from peculiar genetic features of those cells, but from age-dependent cellular selection operating on all B cells. PMID- 8346415 TI - Lactoferrin triggers in vitro proliferation of T cells of Lewis rats submitted to mycobacteria-induced adjuvant arthritis. AB - We have recently reported antigenic (B-cell) cross-reactivity between the mycobacterial 65 kDa heat shock protein (hsp65) and human lactoferrin (LF) and we suggested that this cross-reactivity might have a role in mycobacteria-associated autoimmune disease. Here, we have searched for anti-LF T-cell reactivity in Lewis rats submitted to a mycobacteria-triggered autoaggressive disorder (adjuvant arthritis, AA), an autoimmune disorder characterized by high anti-hsp65 reactivity. We have quantified the in vitro proliferative response to LF of lymph node and spleen cells of Lewis rats killed 9, 14 and 21 days after the immunization with the AA-triggering, mycobacteria-containing adjuvant (complete Freund's adjuvant, CFA). We found that LF induced significant proliferation of lymph node T cells of rats undergoing AA. This T-cell proliferation was not as marked as the one provoked by hsp65; it was, nevertheless, significantly higher (P < 0.05) than that produced by a non-arthritogenic antigen (i.e. albumin). T cells from naive or mineral oil (incomplete Freund's adjuvant, IFA) injected rats did not respond to LF or hsp65. These data indicate that LF may work as an accessory stimulatory factor of the T-cell autoreactivity associated with mycobacteria-induced arthritis. PMID- 8346416 TI - T-cell stimulation with purified mycobacterial antigens in patients and healthy subjects infected with Mycobacterium leprae: secreted antigen 85 is another immunodominant antigen. AB - Peripheral blood leucocytes from 9 paucibacillary and 12 multibacillary leprosy patients, from 18 healthy controls and from 34 healthy leprosy contacts were stimulated with three mycobacterial heat shock proteins with respective molecular weights of 70, 65 and 18 kDa and with the secreted 30-32 kDa protein, also called antigen 85. Antigen 85 was found to be the most powerful T-cell antigen (as measured by lymphoproliferation and IFN-gamma secretion), eliciting a positive response in all (100%) paucibacillary patients and in all lepromin-positive controls and contacts. The three heat shock proteins (hsp) were less active T cell stimuli. Reactivity to the 70 kDa hsp was found in only 44% of the paucibacillary patients, in 80% of the lepromin-positive controls and in 60% of the lepromin-positive leprosy contacts. The 65 kDa hsp stimulated T cells in 89% of the paucibacillary patients and in 80% of the lepromin-positive controls and contacts. Responsiveness to the 18 kDa hsp, finally, was clearly more frequent in tuberculoid leprosy patients (78%) than in lepromin-positive controls (40%) or lepromin-positive leprosy contacts (4%). T-cell reactivity of 8 lepromin-negative controls, of 9 lepromin-negative contacts and of 12 multibacillary leprosy patients was low to all the antigens tested. Although proliferative and IFN-gamma responses were generally closely related, some subjects demonstrated a dissociation of these two immune parameters. Our data confirm previous findings on the powerful T-cell stimulatory properties of antigen 85 during M. leprae infection and suggest that this antigen is indeed a potentially protective T-cell immunogen. PMID- 8346417 TI - Evidence for the role of CR1 (CD35), in addition to CR2 (CD21), in facilitating infection of human T cells with opsonized HIV. AB - Complement activation by HIV results in the binding of C3 fragments to the gp160 complex and enhanced infection of C3 receptor-bearing target cells. We have studied complement-mediated enhancement of infection of the human CD4-positive T cell line HPB-ALL which expresses the CR1 (CD35) and CR2 (CD21) receptors for C3. CR1 and CR2 are present on 15% and 40% of normal peripheral blood CD4-positive T lymphocytes respectively. Opsonization of the virus with complement resulted in a 3- to 10-fold enhancement of infection of HPB-ALL cells, as assessed by measuring the release of p24 antigen in culture supernatants throughout the culture period. Blockade of CR2 with cross-linked anti-CR2 monoclonal antibodies decreased infection to the level observed with unopsonized virus. Blocking CR1 reduced complement-mediated infection by 50-80%. Experiments using serum deficient in complement factor I demonstrated that CR1 mediates the interaction between opsonized virus and T cells in addition to its ability to serve as a cofactor for the cleavage of C3b into smaller fragments that interact with CR2. A requirement for CD4 in complement-mediated enhancement of infection was observed with HIV-1 Bru but not with HIV-1 RF. Thus, CR1 and CR2 contribute in an independent and complementary fashion to penetration of opsonized virus into complement receptor expressing T cells. Involvement of CD4 in infection with opsonized virus depends on the viral strain. PMID- 8346418 TI - Polyreactivity is a property of natural and disease-associated human autoantibodies. AB - Polyreactivity was earlier recognized as a feature of naturally expressed autoantibodies in serum. In the present study, we have compared the reactivity on a panel of self antigens of affinity-purified anti-DNA and anti-thyroglobulin (TG) IgG autoantibodies from the serum of patients with systemic lupus erythematosus (SLE) and autoimmune thyroiditis with their affinity-purified counterparts isolated from the serum of healthy individuals. Anti-DNA autoantibodies exhibited a similar degree of polyreactivity whether originating from patients or from healthy adults. Natural anti-TG autoantibodies were also found to be polyreactive. Anti-TG autoantibodies from patients with Hashimoto's thyroiditis showed little or no polyreactivity. Natural anti-TG autoantibodies were equally polyreactive whether or not they belonged to a fraction of normal IgG that is connected through V regions with other IgG molecules from the same source. These results indicate that polyreactivity of autoantibodies is a feature that does not allow one to distinguish between natural and disease-associated autoantibodies as well as between V-region-connected and unconnected autoantibodies. PMID- 8346419 TI - Interferon-gamma induces a phospholipase D-dependent release of arachidonic acid from endothelial cell membranes: a mechanism for protein kinase C activation. AB - Interferon-gamma (IFN-gamma) induces MHC class II expression on endothelial cells in a protein kinase C (PKC)-dependent manner. Here we show that IFN-gamma induces a sixfold arachidonic acid (AA) release from cultured rat microvascular endothelial cell membranes compared with non-treated cells. Since this result suggests that AA could act as a second messenger for IFN-gamma, we analysed its capacity to directly activate PKC. We have previously shown that IFN-gamma induces a transient, multiphasic activation of PKC via the action of the phospholipase D (PLD) pathway. Here we show that AA is able to activate PKC. In an attempt to characterize the source of the liberated AA after IFN-gamma induction in endothelial cells we used a panel of enzyme inhibitors. The IFN gamma-induced release of AA could not be modified by interfering either with the phospholipase A2 (PLA2) pathway using bromophenacyl bromide (BPB), or with the phospholipase C (PLC) pathway using neomycin. The phosphatidic acid phosphatase (PAPase) inhibitor propranolol, inhibiting the generation of diacylglycerol (DAG) and further AA from phosphatidic acid (PA), could totally down-regulate the IFN gamma-induced release of AA. Since PA is produced solely by the action of PLD from phosphatidylcholine (PC) we conclude that the AA originated from the cell membrane-associated PC. In summary, we show here that IFN-gamma causes the liberation of cell membrane-associated, PC-linked AA. This AA could directly activate PKC in a similar multiphasic manner to IFN-gamma, suggesting that it is a true second messenger for IFN-gamma in cultured endothelial cells. PMID- 8346420 TI - B-cell activation in duodenal mucosa after oral cholera vaccination in IgA deficient subjects with or without IgG subclass deficiency. AB - Alterations in duodenal Ig-producing cells induced by two oral cholera vaccinations were studied by two-colour immunofluorescence in mucosal tissue sections from adults with selective IgA deficiency (IgAD), either with (n = 7) or without (n = 9) frequent infections, infection-prone patients with combined IgAD and IgG subclass deficiency (IgGSD) (n = 7), and normal control subjects (n = 11). The proportion of IgG-producing cells prior to immunization tended to be lower in the symptomatic IgAD subjects than in the clinically healthy ones. In the first subgroup the absolute number of IgG cells per intestinal length unit was significantly increased after immunization (P < 0.04), and this tendency was also observed in the healthy IgAD subjects (6/9) and in those with combined deficiency (5/7). Very few IgAD subjects responded with an increase of IgM producing cells. The normal controls responded variably in all major immunocyte classes, in the order IgA > IgG > IgM. Compared with these controls, the patients with combined IgAD and IgGSD showed significantly increased IgG1 (P < 0.01) and reduced IgG2 (P < 0.006) proportions, which was in accordance with their serum subclass levels. Our study showed that oral cholera vaccination preferentially activates intestinal IgG-producing cells in IgAD subjects. This result agreed with data recently obtained by ELISPOT in the same patients with regard to antibody-forming cells specific for cholera toxin. Both methods suggested that IgG rather than IgM antibodies are elicited as compensation for a lacking IgA response. However, our overall results showed that intestinal B-cell activation is quite variable after oral cholera vaccination. Although such vaccination might be of importance for enhancing mucosal immunity also in IgAD patients, a concurrent gut disease could possibly be aggravated by IgG-mediated mucosal immunopathology in the absence of anti-inflammatory IgA antibodies. PMID- 8346421 TI - [Who should practice psychosomatic medicine?]. PMID- 8346422 TI - [Delay in management and treatment of patients with suspected acute myocardial infarction: role of the public, of extra- and intra-hospital structures and transportation methods]. AB - The potential impact of thrombolytic agents on mortality and morbidity from coronary artery disease is weakened by in- and out-of-hospital delays occurring in the management of acute myocardial infarction. The goals of this study were to review the situation 5 years after the publication of the GISSI study. From October 1, 1991 to March 31, 1992, all the events occurring between symptom onset and in-hospital treatment were analyzed for 620 consecutive patients with suspected myocardial infarction seen in the emergency ward of the University Hospital, Geneva. Among them, 189 (30.5%) had myocardial infarction and 144 (23%) unstable angina. Mean and median delay between symptom onset and hospital arrival for the 620 patients were 10 h 02 min and 2 h 55 min respectively; 117 (19%) patients came straight to the hospital alone, with the risk of arrhythmic complications en route to the emergency ward but with shorter time delays (mean delay: 6 h 13 min; median delay: 2 h 30 min) than the 503 (81%) patients who called out-of-hospital services (mean delay: 10 h 55 min; median delay: 3 h; p < 0.04). The latter patients accounted for 47% of mean out-of-hospital delay and the out-of-hospital services for 53%. Minimization or ignorance of symptoms, waiting for relief from medication and attempts to reach relatives were responsible for long patients' decision times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346424 TI - [Vertebral artery dissection following manipulation of the cervical vertebrae]. AB - We report on two patients who developed symptoms and signs of infarction of dorsolateral medulla oblongata (Wallenberg's syndrome) and the cerebellum respectively, following cervical manipulation for slight neck pain. Subsequent vertebral artery angiography and MRI showed the typical signs of vertebral artery dissection of the atlantoaxial and intracranial segment in one patient, and of the intertransverse segment in the second. The pathogenesis of vertebral artery injury following cervical manipulation is discussed and the literature is reviewed. The practical implications of this rare complication are discussed. PMID- 8346423 TI - [Alpha-interferon therapy in Crohn's disease: initial clinical results]. AB - 4 therapies in 3 patients (1 female, 2 male) suffering from steroid dependent Crohn's disease are described. Interferon alpha-2b was administered for 24 weeks (3 million I.U. per day for 4 weeks, and 3 x 3 million U.I. per week for 20 weeks). Prednisolone dosage at start of therapy depended on initial inflammatory activity (CDAI). The daily dose was reduced stepwise and omitted after 12 weeks. In two courses patients did not respond and therapy had to be halted after 12 and 14 weeks' duration because of increasing disease activity. During the other two treatments a decrease in disease activity of 118 and 70 CDAI units (in both cases after 8 weeks) could be achieved. In particular, the course in one patient with abundant intestinal and extraintestinal inflammatory activity was quite impressive: extraintestinal activity disappeared completely within 10 days, CDAI ameliorated substantially for 30 weeks and the patient could be treated without steroids for a total period of 18 weeks. As a preliminary conclusion from the cases described up to now, it can be speculated that females probably respond more favorably to a combined therapy with interferon alpha and corticosteroids. Moreover, we suggest that the potential of interferon in Crohn's disease might be to overcome a steroid refractory disease state rather than to allow omission of steroid medication which could not be further reduced without exacerbation. Clearly, present experience of interferon therapy in Crohn's disease is still too scarce and more work needs to be done to define the role of interferon in IBD. PMID- 8346425 TI - [Professional management of death--sociocultural aspects]. AB - During recent decades, treatment of death has been removed from the family and placed in the hands of experts and specialized institutions. More and more people die outside their homes. Our statistical analysis shows that in Switzerland between 1969 and 1986 the old people's home has replaced the private home. However the proportion of people dying in the hospital (55%) has not changed. Proceeding from these facts, we conducted a sociological research project with participant observation that explored attitudes, strategies and practices of professionals who deal closely with death and dying. Our case studies involved people working on the wards of a hospital, in a hospital mortuary, in an old people's home, in an autopsy department, in a funeral home and in a cemetery. The analysis showed that in the context of preservation of life (hospital), the consciously maintained attitude is ambivalence and an openness to various outcomes. In the context of applied science (autopsy department), the attitude is search for unequivocal exactness. In the context of loss (funeral home, cemetery), we find two different orientations among two different groups of actors. Those who deal with the practical side of death, such as the crematorium attendant, show a technical orientation, while those who deal with death's non practical side, such as the minister, show a social and a symbolic orientation. At the points of intersection between these contexts, the actors develop complex strategies: maintenance of the past, negation of the present and anticipation of the future. CONCLUSIONS: (1.) The fight against death in the university hospital is being more and more replaced by the development of a strategy of openness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346427 TI - Computing in science. PMID- 8346426 TI - [Concerning: Herzog Ch: quantification of mRNA using the polymerase chan reaction, cytokines in rheumatoid arthritis (Schweiz Med Wochenschr 1992; 122:229)]. PMID- 8346429 TI - Army to test only MicroGeneSys vaccine. PMID- 8346428 TI - Choose your poison. PMID- 8346430 TI - Varmus tapped to head NIH. PMID- 8346431 TI - How Varmus got the job. PMID- 8346433 TI - A Manhattan Project by any other name... PMID- 8346432 TI - Army clears Redfield--but fails to resolve controversy. PMID- 8346434 TI - New piece in Alzheimer's puzzle. PMID- 8346435 TI - Protein signals frog embryo to start getting a head. PMID- 8346436 TI - Beyond databases and E-mail. PMID- 8346437 TI - AI helps researchers find meaning in molecules. PMID- 8346438 TI - The collaboratory opportunity. PMID- 8346439 TI - Genetic algorithms: principles of natural selection applied to computation. AB - A genetic algorithm is a form of evolution that occurs on a computer. Genetic algorithms are a search method that can be used for both solving problems and modeling evolutionary systems. With various mapping techniques and an appropriate measure of fitness, a genetic algorithm can be tailored to evolve a solution for many types of problems, including optimization of a function of determination of the proper order of a sequence. Mathematical analysis has begun to explain how genetic algorithms work and how best to use them. Recently, genetic algorithms have been used to model several natural evolutionary systems, including immune systems. PMID- 8346440 TI - Metal ion-dependent modulation of the dynamics of a designed protein. AB - The peptide alpha 4 is a designed four-helix bundle that contains a highly simplified hydrophobic core composed exclusively of leucine residues; its tertiary structure is therefore largely dictated by hydrophobic forces. This small protein adopts a structure with properties intermediate between those of the native and molten globule states of proteins: it is compact, globular, and has very stable helices, but its apolar side chains are mobile and not as well packed as in many natural proteins. To induce a more native-like state, two Zn(2+)-binding sites were introduced into the protein, thereby replacing some of the non-specific hydrophobic interactions with more geometrically restrictive metal-ligand interactions. In the metal-bound state, this protein has properties that approach those of native proteins. Thus, hydrophobic interactions alone are sufficient to drive polypeptide chain folding nearly to completion, but specific interactions are required for a unique structure. PMID- 8346441 TI - Determinants of binding-site specificity among yeast C6 zinc cluster proteins. AB - Related DNA binding proteins often recognize similar DNA sites but can distinguish among them with the use of different protein-DNA contacts. Here, it is shown that members of the C6 zinc cluster family of yeast transcriptional activators distinguish related DNA sites by a different mechanism. The DNA binding site for each of these proteins contains identical nucleotide triplets (CGG ... CCG) but differs in the spacings between the triplets. It is shown that zinc clusters of these proteins work interchangeably to recognize the conserved triplets and that the region 19 amino acids to the carboxyl-terminal side of the zinc cluster, comprising the linker and the beginning of a dimerization element as inferred from the GAL4 crystal structure, directs the protein to its preferred site. PMID- 8346442 TI - Reconstitution of T cell receptor zeta-mediated calcium mobilization in nonlymphoid cells. AB - T cell antigen receptor (TCR) activation involves interactions between receptor subunits and nonreceptor protein tyrosine kinases (PTKs). Early steps in signaling through the zeta chain of the TCR were examined in transfected COS-1 cells. Coexpression of the PTK p59fynT, but not p56lck, with zeta or with a homodimeric TCR beta-zeta fusion protein produced tyrosine phosphorylation of both zeta and phospholipase C (PLC)-gamma 1, as well as calcium ion mobilization in response to receptor cross-linking. CD45 coexpression enhanced these effects. No requirement for the PTKZAP-70 was observed. Thus, p59fynT may link zeta directly to the PLC-gamma 1 activation pathway. PMID- 8346444 TI - Delegation. PMID- 8346445 TI - ANA concerned at growing RN layoffs. PMID- 8346443 TI - Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. AB - The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80. PMID- 8346446 TI - Black dog and nursing diagnosis. PMID- 8346447 TI - Primary health care: the nurse solution. PMID- 8346448 TI - Professional practice: standards, code, and accountability. PMID- 8346449 TI - Code for nurses. PMID- 8346450 TI - [Correction of double-outlet right ventricle using the Kawashima intraventricular tunnel procedure]. AB - Anatomical correction with an intraventricular tunnel, as suggested by Kawashima, was performed in 14 children with a double-outlet right ventricle and a subpulmonary (4) or non-committed (10) defect of the ventricular septum with one early and one late death. Nine children had previous palliative operations. Complications after radical surgery were residual ventricular defects (4), infectious endocarditis (2) and impaired rhythm (one sudden death). Twelve patients are after medium- term or long-term follow-up free from subjective complaints, ten children report good performance, in two the performance is slightly reduced. Anatomical intraventricular correction of double-outlet right ventricle restores the mitral valve and left ventricle to the systemic circulation. The prognosis of children with double-outlet right ventricle and subpulmonary or remote ventricular defect improves substantially. PMID- 8346451 TI - [Peroperative transluminal angioplasty as a supplementary procedure to arterial reconstruction surgery]. AB - Patients with affections of the vascular system of the lower extremities at several levels present a complicated problem for vascular surgery. The authors submit their experience with a combination of vascular reconstruction and peroperative transluminal angioplasty. In 25 patients, mean age 64 years, they performed 29 of these combined operations, 10 times on account of claudications, 11 times on account of pain at rest, 8 times on account of trophic defects. The pelvic vessels were dilated 6 times; the dilated vessels as well as the reconstruction remained patent. Peroperative angioplasty of the superficial femoral artery was performed 6 times, occlusion occurred once. Twelve times they dilated the distal portion of the popliteal artery or the vessels of the leg, 3 times the dilated portion became occluded. None of the patients lost the limb, one patient died from acute myocardial infarction shortly after operation. The authors describe the technique of peroperative transluminal angioplasty, evaluate the results and discuss the advantages and disadvantages of this method. PMID- 8346452 TI - [Injuries of the bile ducts and fundamentals of therapy]. AB - In the submitted paper the authors present an account on 88 patients with reconstructions of the biliary pathways, most frequently after iatrogenic damage. Check-up examinations revealed that the results in patients who survive for prolonged periods and were reoperated in time, unless they developed irreversible liver damage, are very satisfactory. 81.8% of the patients have no subjective complaints and the objective finding (laboratory examination, HIDA) is consistent with the subjective report. In the author's opinion a certain part in these satisfactory long-term results is played by short-term, or if necessary, long term drainage of the anastomosis. This problem is discussed in detail. PMID- 8346453 TI - [Changes in hemocoagulation in children with cranio-cerebral trauma]. AB - The authors monitored in children with craniocerebral injuries hospitalized in their department in the course of the more than one-year existence of the child ARO ward in addition to other vital parameters also changes of the haemocoagulation system. They describe the majority of commonly observed abnormalities as "latent consumption coagulopathy", where laboratory findings are not associated with clinical signs of coagulopathy. On the other end of the spectrum of coagulopathies after head injuries is the unit of disseminated consumption coagulopathy which is generally evaluated as a secondary phenomenon or as an intermediary mechanism of the disease which complicates various pathological conditions incl. craniocerebral injuries. The authors discuss the pathophysiology, diagnostic possibilities and their experience with the treatment of the mentioned disorders. PMID- 8346454 TI - [Treatment of peripheral nerves in a district hospital]. AB - The authors submit the results of 23 operations performed on peripheral nerves of the upper extremity in a district hospital. They emphasize the good cooperation of the surgeon with the neurologist, the importance of clinical and EMG examinations for diagnosis as well as during evaluation of the accomplished operation. In cooperation with the Physical Institute of the Czech Academy of Sciences it proved possible to reconstruct for surgical purposes a common colposcope so that it can be used for microsurgical operations. A brief description of the apparatus is given in the paper. From a total of 23 performed operations a satisfactory result was recorded in 87% of the operated patients. PMID- 8346455 TI - [Urologic complications in colorectal carcinoma]. AB - Urological complications of colorectal cancer during surgery of the large bowel are relatively frequent. Fortunately these complications are as a rule transient and recede either spontaneously or after a suitably selected therapeutic procedure. Permanent complications account in our group comprising 311 patients only for a fraction of a per cent. The problem of carcinoma of the colon and rectum and treatment, along with possible complications, is becoming increasingly important in particular in conjunction with an objectively assessed shift of the prevalence of the disease to younger age groups. The group of patients treated in the authors' department on account of colorectal carcinoma during the last five years was evaluated in detail and thus it was possible to detect why different complications developed. This evaluation of all recorded cases was made from the diagnostic aspect as well as with regard to therapeutic possibilities, taking into account the technique of surgical approaches. PMID- 8346456 TI - [Short-term hospitalization and ambulatory care of patients with advanced hemorrhoidal disease]. AB - The authors describe possible non-surgical treatment of extensive haemorrhoids grade 3 and 4, using Barron's rubber band ligation. To make comparison of therapeutic results possible Dennison's Sheffield classification is used. In the mentioned new approach indications for ambulatory treatment or short-term hospitalization in patients with an advanced grade of internal or external haemorrhoids are extended. From a group of 145 patients treated by this method 126 were free of subjective complains during a check-up 12 months after termination of treatment. PMID- 8346457 TI - [Excellent therapeutic results in an "apparently hopeless case"--an example of good interprofessional cooperation]. AB - The authors demonstrate on the example of a patient the correct procedure as regards collaboration between different departments with excellent results- survival and cure of the patient. It was a serious case where the patient with the basic diagnosis (acute phlegmon of the neck with an abscedent mediastinitis) and several serious associated complications theoretically did not have a chance of survival. The authors emphasize the importance of collaboration of different departments where each played in a certain stage of the disease a leading role in therapy. PMID- 8346459 TI - [2 comments on terminology relating to the large intestine]. PMID- 8346458 TI - [Fatal surgical complications in obstetrics]. PMID- 8346460 TI - [A years' experience in working with the General Health Insurance Company]. PMID- 8346461 TI - [Thinking about rheumatic diseases in childhood]. PMID- 8346462 TI - [Cause of death in autopsied RA patients]. AB - A mortality study was performed based on the data of Annual of the Pathological Autopsy Cases in Japan in 1985-1989. The average life span of the RA patients, revealing 66.5 years in male and 64.6 years in female, was shorter than that of general population in Japan. Of 1,246 autopsied RA cases, the most common causes of death were infections (26.6%), respiratory diseases including interstitial lung disease (17.5%) and amyloidosis (12.5%). Amyloidosis was common among RA cases (25.2%), and it was suggested that RA was the most important underlying disorder of the secondary amyloidosis: in 1985 to 1989, 316 cases of 515 secondary amyloidosis (61.4%) were associated with RA. PMID- 8346463 TI - [Clinicopathological evaluation and treatment of bucillamine induced membranous nephropathy]. AB - We discussed clinicopathological evaluation and treatment of bucillamine induced renal destruction. Thirteen cases of rheumatoid arthritis were investigated in whom proteinuria had developed while being treated with bucillamine. The dose of bucillamine ranged from 100 to 300 mg/day, and many of them were treated with a dose of 200-300 mg/day. The total dose was in the range of 9-57 g. Proteinuria had developed within 3 months after perceiving the efficacy of bucillamine in many of the cases. The details of renal histology revealed that membranous nephropathy was noted in all of the 13 cases and that mesangial proliferative gromerulonephritis was noted in eight cases (61.5%), thin basement membrane was noted in four cases (30.8%) and in one case (7.7%) amyloidosis were identified in parallel. After suspending further administration of bucillamine, the proteinuria was gradually reduced without any specific treatment or without increase in the dose of corticosteroid, and was eliminated in all cases within 10 months. There were some cases in whom proteinuria was eliminated within a short period of time by the administration of corticosteroid in a moderate dose (prednisolone 30 mg/day). It is necessary to initiate the administration of bucillamine from a small dose such as 100 mg/day and pay attention to onset of any side effect. It was also seemed necessary to confirm the renal histology by renal biopsy as far as feasible because a large variety of pathological findings are developed in the kidney of these cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346464 TI - [Terminal phalangeal osteosclerosis in rheumatoid arthritis]. AB - OBJECTIVE: Osteosclerosis of the terminal phalanges of the hand has been reported in the collagen diseases including rheumatoid arthritis (RA). The current study was made to clarify the significance of terminal phalangeal osteosclerosis in RA. METHODS: Hand x-ray films of 108 patients (male 13, female 95) with RA for more than 10 years were assessed by Halim's grading. Grade 2, (Distance between both cortices is < 1 mm but there is still an intermediate space discernible), and grade 3, (Complete fusion of both cortices, but the base of the terminal phalanx is open), were classified as the positive group. Grades 0 and 1 were classified as the negative group. Both groups were compared and sigma GS/D values was measured at terminal phalanges, middle phalanges and metacarpuses of right middle fingers using digital image processing method. sigma GS/D index was calculated as being equal to the ratio of sigma GS/D value of the terminal or middle phalanx to sigma GS/D value of the metacarpus. RESULTS: Thirty cases (28%) were positive (male 1, female 29). Osteosclerosis of terminal phalanges usually appeared in more than two digits bilaterally. It was located as follows; thumb-1 case, index 13 cases, middle-24 cases, ring-51 cases, little-58 cases. Obliteration of the medullary space of middle phalanges was seen in 5 cases. No difference was observed between the positive and negative groups about sex, age, the mean value of C-reactive protein, the incidence of Steinblocker's class classification and the rate of seropositive patients. Osteosclerosis of terminal phalanges was observed at first consultation in 93% of positive cases. Osteosclerosis is expected to appear in the early phase of RA and to last for more than 10 years. sigma GS/D index of the positive group (1.03 +/- 0.24, mean +/- SD) was greater than that of the negative group (0.63 +/- 0.25) (p < 0.05). PMID- 8346465 TI - [Soluble IL-2 receptor levels in rheumatic diseases]. AB - We measured soluble interleukin-2 receptors (sIL-2R) in plasma and/or joint fluid (JF) from patients with rheumatoid arthritis (RA: 16 patients), Sjogren's syndrome (SS: 24 patients) and Behcet's disease (BD: 23 patients). Plasma sIL-2R levels were significantly higher in RA patients (956 +/- 994 U/ml, p < 0.01) and SS patients (1025 +/- 1112 U/ml, p < 0.01) than 20 healthy subjects (338 +/- 159 U/ml), but not significantly increased in BD patients (408 +/- 329 U/ml). sIL-2R levels higher than the mean of healthy subjects +2 standard deviations were observed in 3 BD patients (13.0%), 7 RA patients (43.8%) and 10 SS patients (41.7%). sIL-2R levels positively correlated with erythrocyte sedimentation rates and C-reactive protein levels in RA patients, or IgM levels in SS. There was no significant correlation between plasma sIL-2R levels and disease activity, clinical symptoms, or other laboratory parameters in BD patients. However, sIL-2R concentrations in the JF from 4 BD patients (1644 +/- 198 U/ml: p < 0.05) or 16 RA patients (3946 +/- 5424 U/ml: p < 0.01) were significantly higher than corresponding plasma sIL-2R concentrations. Above results indicate that lymphocytes are being activated in patients with RA or SS and in the inflammatory lesions of BD patients, while the whole immunologic activation are relatively lower in BD than RA and SS. PMID- 8346466 TI - [Vasculitis-related acute abdomen in systemic lupus erythematosus--ultrasound appearances in lupus patients with intra-abdominal vasculitis]. AB - Although an acute abdomen often occurs in lupus patients, definitive treatment is commonly delayed due to the difficulty in diagnosis. We performed an abdominal ultrasound (US) in two patients with severe abdominal pain and recognized mural thickenings of intestinal walls. In the first case high dose prednisone was given for severe abdominal pain, with subsequent perforation of sigmoid colon. Pathological specimens showed a thrombotic vasculitis in the mesenteric artery and arteriole of intestinal walls. In the second case physical examination elicited a rebound tenderness. An abdominal X-ray demonstrated a gasless ileus and US also showed marked thickening of intestinal walls, 16 mm in thickness. A CT scan revealed the same findings in the entire bowel. After high dose methylprednisolone was administered, her symptoms markedly improved. The mural thickenings disappeared within 10 days as seen by abdominal ultrasound examination. The US is very useful in order to make an early diagnosis of intestinal vasculitis, showing as edema (but non-specific) of intestinal wall and we can use it safely and repetitively without exposure to radiation, compared with other examinations, such as CT scan and gastrointestinal contrast study etc. The US is not only useful in diagnosis, but also helpful for follow up of patients after the initiation of treatment. PMID- 8346467 TI - [Success of cyclosporine therapy in two patients with PSS]. AB - Two PSS patients, unresponsive to D-penicillamine, steroid, cyclophosphamide and plasma exchange therapy, were treated with cyclosporine. One patient complained scleroderma, dysphagia and dyspnea during movement after treatment with steroid, plasma exchange and cyclophosphamide. He showed a increased Leu3a/2a ratio (6.72). About 3 months after treatment with cyclosporine, these complain decreased with normalization of elevated Leu 3 a/2 a ratio. 1 year after treatment, %DLco increased 86% from 50% and pneumonitis findings of chest X-ray and chest CT were also improved. Another patient who complained Raynaud's phenomenon and scleroderma which had extended over his abdomen despite treatment with steroid and cyclophosphamide. 1 month after treatment with cyclosporine, improvement of these phenomenon were recognized. It is concluded that cyclosporine can be an effective agent in the treatment of PSS. PMID- 8346469 TI - [Allergic granulomatosis and angiitis associated with intestinal perforation and eye movement disorder]. AB - A perforation in the small intestine and one and a half syndrome were observed in 45-year-old male with allergic granulomatosis and angiitis (AGA). The patient was first admitted to our hospital in 1988 with complaints of bronchial asthma and an abnormal density on his chest X ray. The diagnosis of PIE syndrome was made based on marked peripheral blood eosinophilia. He was successfully treated with prednisolone and had been well on the maintenance therapy of small doses of it. In May 1990, peripheral neuropathy occurred in his bilateral lower legs and it was followed by nausea and vomiting. The laboratory findings on admission showed leukocytosis (19,300/mm3) with 43% eosinophilia and elevated blood level of IgE (3000 IU/ml). On the tenth day of admission, ileus symptom and subsequently a perforation of the small intestine were observed. The mesenterial specimens obtained during the emergency operation showed the findings compatible with AGA. Remission of AGA was induced by the treatment with 60 mg prednisolone and 100 mg cyclophosphamide per day following methylprednisolone pulse therapy. He was well on maintenance prednisolone until June 1991, when he suddenly developed one and a half syndrome. Although cranial CT scan and MRI showed no abnormal findings, cyclophosphamide therapy was resumed and prednisolone was increased because microangiopathy due to AGA was thought to be the cause of this central nervous system symptom. The one and a half syndrome improved with this therapy. This case suggests that the long term treatment with prednisolone and cyclophosphamide would be indicated in the severe AGA with close monitoring of the symptoms and peripheral blood eosinophilia. PMID- 8346468 TI - [A case of Sjogren's syndrome accompanied by lymphadenopathy and IgG4 hypergammaglobulinemia]. AB - A 78-year-old male patient suffered from slight dryness of his mouth and eyes, which was followed by swelling of the parotid and submandibular glands on both sides. Subsequently, he developed generalized lymphadenopathy accompanied by hypergammaglobulinemia IgG 7740 mg/dl, main subclass: IgG4, 5800 mg/dl. Histopathological examination of lymph nodes from his left neck showed follicular proliferation of plasma cells containing cytoplasmic kappa and lambda chains of IgG4, without destruction of the lymph node structure. His serum showed very low levels of complement: 0 U/ml of CH 50, 14 mg/ml of C3 and less than 11 mg/ml of C4. During treatment with prednisolone at 30 mg/day, the swelling of the salivary glands and lymph nodes reduced the IgG and IgG4 decreased and the complement increased. Finally, all lymph nodes, IgG and complement abnormalities were normalized. Anticomplementariness of IgG4 was demonstrated in this patient. PMID- 8346470 TI - [Anticardiolipin antibodies do not recognize cardiolipin antigen]. PMID- 8346471 TI - Some thoughts concerning the position of neurosurgery in the last decade of the 20th century. PMID- 8346472 TI - Distribution of intrathecally administered ACNU in mongrel dogs: pharmacokinetics and quantitative autoradiographic study. AB - The pharmacokinetics of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2 chloroethyl)-3-nitrosourea (ACNU) in the cerebrospinal fluid (CSF), were determined in dogs after ventriculolumbar perfusion (VLP, n = 6), and bolus injection into the ventricle (VB, n = 2), cisterna magna (MB, n = 5), and lumbar cistern (LB, n = 3), by high-performance liquid chromatography. The VLP method introduced effective amounts of ACNU into the lumbar cistern for cell kill in vitro. That is, the areas under the time concentration curve (AUC) of ACNU in the lumbar CSF for those receiving a 1.5 mg perfusion of ACNU were 481, 791, and 520 micrograms.min/ml and those receiving a 5 mg perfusion were 1,081, 2,048, and 1,215 micrograms.min/ml, respectively. These values were superior to 3-log cell kill condition of 9L gliosarcoma and 1.5-log cell kill of HU-126 human glioma cell line. Among the groups to which 5 mg of ACNU was administered, the VLP method attained significantly higher AUC values in the lumbar CSF than MB method. Quantitative autoradiography using an imaging plate system was performed in the VLP group (n = 2), VB group (n = 1), MB group (n = 2), and LB group (n = 2) using a 10 microCi/kg [ethylene-14C] ACNU dose which is thought to be related to the alkylating activity of ACNU. The VLP method attained a stable and abundant distribution of ACNU in the neural axis from the ventricular cavity to the lumbar cistern, but the cerebral convexity surface was devoid of a significant level of ACNU. When the MB method was used, the pharmacokinetic data varied in the cisterna magna and lumbar region, and again no significant level of ACNU was detected in the ventricular cavity. With the LB method, although a rich distribution was detected in the spinal cord, the concentration decreased abruptly at the upper cervical level. The VB method was unsatisfactory for obtaining an effective amount of ACNU in the lumbar region. The research and testing to date indicate that the VLP method is the procedure of choice in the treatment of meningeal dissemination. PMID- 8346473 TI - Role of hypervolemic hemodilution in focal cerebral ischemia of rats. AB - This study was designed to better define a protocol for hypervolemic hemodilution in acute cerebral ischemia and investigate the mechanism of action of this therapy. Anesthetized rats (n = 40) were subjected to 6 h of middle cerebral artery (MCA) occlusion. At 45 min after MCA occlusion, each rat received one of the following treatment modalities: (1) control, (2) isovolemic hemodilution, (3) hypervolemic nonhemodilution (whole blood), (4) hypervolemic hemodilution (normal saline), and (5) hypervolemic hemodilution (hetastarch). Local cerebral blood flow (CBF) was determined with hydrogen clearance technique, and cardiac output was assessed by measuring the descending aorta blood flow (DAF). Infarction volume was estimated by 2,3,5-triphenyltetrazolium chloride staining method. Hetastarch infusion increased both DAF and local CBF more than the other treatments, by 98% and by 89%, respectively. Hetastarch also reduced infarction volume the most to 71 +/- 19 mm3 (p < 0.01 versus control 117 +/- 32 mm3). A significant correlation between percent (%) changes in local CBF and % changes in DAF existed in ischemic brain regions, and the hetastarch infusion improved local CBF more prominently in profoundly ischemic regions in contrast to isovolemic hemodilution. These data demonstrated the superiority of hypervolemic hemodilution with hetastarch as compared to other similar treatment modalities for acute cerebral ischemia, and indicate that cardiac output augmentation may be more responsible than decreased blood viscosity for the beneficial effect of hypervolemic hemodilution on local CBF in profoundly ischemic regions, as such ischemic brain tissue can severely lose its regulatory control of CBF to alterations in cardiac output. PMID- 8346474 TI - Changes in epidemiology of acute spinal cord injury from 1947 to 1981. AB - The aim of this study was to determine whether there have been epidemiologic changes in acute spinal cord injury. Two groups of patients injured in the same geographic area were compared: the first group of 351 patients was injured between 1947 and 1973; and the second group of 201 patients between 1974 and 1981. The results showed that there were indeed major epidemiologic changes in spinal cord injury between the two study periods. Most importantly, the more recently injured group were younger, arrived sooner, had less severe cord injuries, and higher frequencies of motor vehicle, and sports and recreational accidents, but fewer work-related injuries. PMID- 8346475 TI - Correlation between somatosensory-evoked potentials and magnetic resonance imaging of focal cerebral ischemia in cats. AB - Serial measurements of somatosensory-evoked potentials (SEPs) and magnetic resonance imaging (MRI) were performed in 17 cats for 24 h after unilateral middle cerebral artery occlusion. Intravoxel incoherent motion (IVIM) imaging demonstrated ischemic cerebral injury 2 h post-occlusion in all cats, while T2 weighted imaging failed to show clear evidence of injury until 2-6 h. In the severely affected group of eight cats as determined by SEP criteria, ischemic injury evaluated by MR imaging was detected extensively in not only the basal ganglia but also the frontoparietal cortex including part of the somatosensory center. In contrast, in the mildly affected group of nine other cats, ischemic injury was limited to the basal ganglia with or without some involvement of the lower temporal cortex. The quantitative signal intensity ratios in the frontoparietal cortex were significantly greater in the severely affected group than in the mildly affected group, but showed no difference between them in the basal ganglia. PMID- 8346476 TI - Cytogenetic findings in pituitary adenoma: results of a pilot study. AB - Pituitary adenomas are the most common tumors of the sellar region and are, with rare exception, benign neoplasms. The natural history of these lesions is only poorly understood and, although histologic, immunocytologic, and ultrastructural characteristics have been well established, predicting the natural history of individual tumors is, at best, unreliable. In an effort to better characterize pituitary adenomas, we have analyzed the karyotypes of 18 surgical specimens and attempted to correlate with the morphologic appearance and the clinical data, for example, endocrinologic subtypes, histology, and tumor invasiveness. Most hormonal subtypes were studied including seven growth hormone-prolactin (GH-PRL), two Prolactin (PRL), two Adrenocorticotrophin (ACTH), seven nonsecretory (NULL). No correlations with morphology or invasiveness could be made. Of 7 null cell adenomas, five (71%) had normal karyotypes, whereas of 11 hormone-secreting adenomas three (28%) were normal. Of seven tumors with mixed GH-PRL activity, six had abnormal karyotypes. At least three chromosomes harbored abnormalities shared by more than two tumors. The results demonstrate that chromosome abnormalities are also found in benign tumors. These findings, however, suggest that hormone secreting adenomas may be more likely to be associated with karyotypic abnormalities especially those of the GH-PRL variety. Genetic abnormalities associated with chromosomes 1, 4, 7, and 19 were common and warrant further investigation. PMID- 8346477 TI - Aqueductal stenosis due to mesencephalic venous malformation: case report. AB - The authors report the case of a 43-year-old woman with a venous malformation of the mesencephalon occluding the sylvian aqueduct. Neuroradiological investigations suggested aqueductal stenosis, while the presence of a venous malformation was diagnosed by both magnetic resonance imaging and an angiogram, and was visualized using a neuroendoscope. This is the first reported instance of a venous malformation being observed in situ and the subependymal course taken. PMID- 8346478 TI - Syrinx-fourth ventricle and lateral ventricle-peritoneal shunts for congenital hydrocephalus with syringobulbia and syringomyelia: case report. AB - A case of congenital hydrocephalus with syringobulbia and syringomyelia was reported. Although his neurological condition had deteriorated because of shunt malfunction, progressing syringobulbia, and syringomyelia, he recovered because of the direct communication from the syrinx in the medulla to the fourth ventricle, the shunt from the syrinx in the cervical spinal cord to the fourth ventricle, and the lateral ventriculoperitoneal shunt. PMID- 8346479 TI - A case of vessel perforation during interventional neuroradiological procedure. Operative findings of the perforated vessel. AB - A case of vessel perforation by a guide wire during an interventional neuroradiological procedure is reported. The patient was a 59-year-old woman with a left frontal basal arteriovenous malformation (AVM) fed by the left anterior cerebral artery. Transarterial embolization of the AVM was attempted. During the procedure, vessel perforation by the guide wire occurred at the left A1-A2 junction and resulted in subarachnoid hemorrhage, which stopped spontaneously. The patient developed progressive obstructive hydrocephalus, and surgical treatment was performed. The AVM was totally removed after ventricular drainage, and the arterial perforation site was explored. When clot around the left A1-A2 junction was removed, hemorrhage recurred. This hemorrhage was similar to what has been observed when a small perforating artery was avulsed. The hemorrhage site was coagulated under temporary occlusion of both A1 segments. Surgical intervention was probably not necessary for this type of bleeding if it had stopped spontaneously, because the rebleeding from the small pinhole would be unlikely, and the operation was more hazardous than the usual aneurysmal surgery. PMID- 8346480 TI - Complex occipital arteriovenous fistula associated with neurofibromatosis treated by embolization and surgery. Case report. AB - It is well known that neurofibromatosis is associated with various types of arteriovenous fistulas (AVF), but association with an occipital AVF has not been reported. We are reporting this case which was successfully treated with a combination of embolization and surgery. Superselective angiography defines the anatomic details of the fistula and intraoperative digital subtraction angiography (DSA) facilitates the surgery to cure the fistula. It is important to identify the best therapeutic options using angiographic information to treat a complex arteriovenous fistula. PMID- 8346481 TI - Emergent aneurysmal surgery without preoperative angiography: usefulness of the intraoperative portable digital subtraction angiography. AB - A 42-year-old male with subarachnoid and large intracerebral hemorrhage in coma was operated without preoperative angiography because of impending cerebral herniation. After emergent decompressive craniotomy, intraoperative digital subtraction angiography (DSA) was performed and a middle cerebral artery aneurysm was demonstrated clearly. Aneurysmal neck clipping was successfully performed, and the patient made a good recovery and returned to almost independent activity with minimal hemiparesis. The prognosis of patients with ruptured aneurysm with large intracerebral hematoma is affected by early hematoma evacuation. Since the time spent for preoperative angiography may cause irreversible damage to the brain stem, in such case, early decompressive procedure and subsequent aneurysm diagnosis by intraoperative DSA may be used as alternative method to achieve a good outcome. PMID- 8346482 TI - Occipitocervical fixation in nontraumatic upper cervical spine instability. AB - Ten patients requiring occipitocervical fixation were reviewed: five were unstable secondary to rheumatoid arthritis, one had Klippel-Feil, and four had neoplastic disease. Patients with nonneoplastic disease improved, having decreased pain, decreased paresthesias, and increased ambulation. Patients with neoplastic disease improved significantly after the surgery, but eventually died from different tumors. The technique found to be most efficient was the placement of an intraoperatively contoured Luque rectangle wired from the occiput to appropriate cervical spine levels. PMID- 8346483 TI - Following the course of chronic subdurals in adults. PMID- 8346484 TI - Osteoporosis and cystic fibrosis. PMID- 8346485 TI - Bone mineral density and body composition in adult patients with cystic fibrosis. AB - BACKGROUND: Cystic fibrosis is a multisystem disease characterised by chronic pulmonary sepsis and malnutrition. To ascertain whether osteoporosis is a feature of cystic fibrosis in adult patients, total body and regional bone mineral density (BMD) was measured in a group of eight men and eight women aged 17-42 years. METHODS: Total body and regional BMD (lumbar spine L2-L4, femoral neck, trochanteric, and Ward's triangle), as well as total body fat and lean mass, were measured by dual energy x ray absorptiometry. A range of biochemical, lifestyle, and anthropometric variables was also assessed. RESULTS: Patients with cystic fibrosis had significantly reduced bone density at all sites compared with normal young adults. The mean reductions ranged from 7% at Ward's triangle to 13% at the trochanter. Body mass index (BMI) was positively correlated with BMD at four sites and disease severity negatively correlated with BMD at two sites. Other biochemical and anthropometric variables were not predictive of bone density. Total body fat mass was reduced by 30% compared with normal young adults. CONCLUSIONS: Bone density is decreased in adult patients with cystic fibrosis and BMI and disease severity are independent predictors of bone density. PMID- 8346486 TI - Effect of a platelet activating factor antagonist, WEB 2086, on allergen induced asthmatic responses. AB - BACKGROUND: Platelet activating factor (PAF) has been implicated in the pathogenesis of airway hyperresponsiveness in asthma. The purpose of this study was to evaluate the effects of a selective PAF antagonist (WEB 2086), given in doses known to antagonise the effects of inhaled PAF in human subjects, on allergen induced early and late asthmatic responses and on airway hyperresponsiveness. METHODS: Eight atopic, mildly asthmatic subjects were studied during a screening period and two treatment periods. During the screening period subjects inhaled an allergen to which they were known to be sensitised and the response was measured as the fall in the forced expired volume in one second (FEV1) to show the presence of early (0-1 h) and late (3-7 h) asthmatic responses. On another day the subjects inhaled allergen diluent. During the treatment periods subjects inhaled allergen after one week's pretreatment with WEB 2086 (100 mg three times a day) or placebo administered in a randomised, double blind, crossover fashion. Histamine airway responsiveness was measured 24 hours before and 24 hours after allergen and the results were expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). RESULTS: The maximal early asthmatic response after allergen with placebo treatment was 18.4% (SE 4.4%) and with WEB 2086 18.9% (4.4%). The maximal late response with placebo treatment was 21.7% (5.3%) and with WEB 2086 21.2% (3.0%). The log difference (before and after allergen) in histamine PC20 was 0.35 (0.06) after placebo treatment and 0.30 (0.1) after WEB 2086. CONCLUSIONS: These results indicate that one week of treatment with an orally administered PAF antagonist (WEB 2086) does not attenuate allergen induced early or late responses or airway hyperresponsiveness. PMID- 8346487 TI - Effects of high doses of inhaled corticosteroids on adrenal function in children with severe persistent asthma. AB - BACKGROUND: Childhood asthma generally responds well to inhaled corticosteroids within the dosage range recommended by the manufacturers, but it is sometimes necessary to use higher doses--that is, above 400 micrograms/day--a practice which has become more widespread recently. Whereas the lack of adrenal suppression in children given inhaled corticosteroids in normal doses is well documented, little is known about the effects of higher doses. METHODS: The effects on adrenal function of high dose (above 400 micrograms/day) inhaled corticosteroids were evaluated by measuring cortisol concentration in the morning and performing a short tetracosactrin test in 49 children taking budesonide (mean age 9.2 years (range 4 to 16 years) and 28 children taking beclomethasone dipropionate (10.2 years (5 to 13 years)). Twenty three non-asthmatic children (8.9 years (4.9 to 13 years)) who were under investigation for short stature served as controls for the study. RESULTS: Compared with controls mean basal cortisol concentration was lower in children taking budesonide and beclomethasone dipropionate (control 401 (26.8) nmol/l, budesonide 284 (22) nmol/l, beclomethasone dipropionate 279 (23.2) nmol/l). Sixteen of the 49 children taking budesonide had subnormal basal cortisol concentrations compared with seven of the 28 taking beclomethasone dipropionate. Mean stimulated cortisol concentrations were lower in children taking inhaled corticosteroids than in controls, with no difference between those taking budesonide or beclomethasone dipropionate. CONCLUSIONS: Adrenal suppression occurs in some children who are given inhaled corticosteroids in doses greater than 400 micrograms/day. It may therefore be advisable to try alternative treatments before such doses are used. PMID- 8346488 TI - Improvement in sodium cromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drug. AB - BACKGROUND: Aerosols generated from metered dose inhalers may be highly charged. The aim of this study was to determine whether lining the walls of a polycarbonate spacer device with an antistatic agent would result in an increase in drug output. The effects of multiple actuations of drug into the spacer device and increasing residence time of drug within the spacer were also determined. METHODS: The amount of sodium cromoglycate contained in particles of various size available for inhalation (per 5 mg actuation) from a 750 ml polycarbonate spacer was determined by impinger measurement and spectrophotometric assay. RESULTS: Lining the spacer with an antistatic agent increased the mean (SD) amount of sodium cromoglycate in particles < 5 microns available for inhalation (per 5 mg actuation) by 244% from (0.59 (0.03) to 1.44 (0.2) mg). When there was a 20 second interval between actuation into the spacer device and inhalation, sodium cromoglycate available for inhalation in particles < 5 micrograms decreased by 67% (from 0.59 (0.03) mg to 0.2 (0.01) mg). Use of the spacer device increased sodium cromoglycate available for inhalation in respirable particles (< 5 microns) by 18% compared with direct delivery by metered dose inhaler. Multiple actuations into the spacer decreased the amount of sodium cromoglycate available for inhalation in particles < 5 microns by 31% after two actuations and 56% after three acutations. CONCLUSIONS: Multiple actuations of sodium cromoglycate into a spacer device before inhalation should be avoided, and inhalation from spacer devices should take place immediately after actuation to ensure maximum dose. Lining of a standard spacer device with an antistatic agent significantly increased output of sodium cromoglycate. This may have implications for improved therapeutic response and drug cost. PMID- 8346489 TI - Investigations of an optimal inhaler technique with the use of urinary salbutamol excretion as a measure of relative bioavailability to the lung. AB - BACKGROUND: A simple non-invasive method, in which a urine sample is taken 30 minutes after drug administration, has previously been shown to be a measure of the relative bioavailability of salbutamol to the lungs. This technique has been used to determine an optimal inhaler technique with commercially available metered dose inhalers (MDI). METHODS: Ten healthy subjects were trained in the use of MDIs. Each inhaled 4 x 100 micrograms salbutamol in a series of experiments to examine the relative bioavailability to the lung after different respiratory manoeuvres. Urine collection intervals were 0-0.5 hours and 0.5-24 hours after administration. RESULTS: There was significantly greater elimination of unchanged salbutamol 30 minutes after administration, indicating a greater relative bioavailability of salbutamol to the lungs after (1) exhaling gently to residual volume rather than to functional residual capacity before inhalation; (2) slow inhalation (10 l/min) compared with fast inhalation (50 l/min); (3) breath holding for 10 seconds after inhalation compared with no breath holding. CONCLUSIONS: All patient information leaflets and healthcare personnel should standardise the instructions given to patients and should adopt the inhalation method proposed. PMID- 8346490 TI - Time course and duration of bronchodilatation with formoterol dry powder in patients with stable asthma. AB - BACKGROUND: Formoterol, a new beta 2 agonist, is long and fast acting when given as an aerosol. The aim was to determine the onset and duration of bronchodilatation with formoterol as a dry powder compared with salbutamol dry powder and with placebo. METHODS: Fifteen patients with stable asthma with a reversibility of 15% or more participated in a double blind, within patient study. On five different days the patients received formoterol 6 micrograms, 12 micrograms, or 24 micrograms, salbutamol 400 micrograms, or placebo in random order. Forced expiratory volume in one second (FEV1) was measured 10 minutes before, 30 minutes after, and then every hour for up to 12 hours after treatment. Specific airway resistance (sRaw) and specific airway conductance (sGaw) were measured immediately before and one, three, five, 10, 15, and 30 minutes after treatment. RESULTS: Formoterol 12 micrograms and 24 micrograms caused bronchodilatation as rapidly as salbutamol 400 micrograms. Peak values were not significantly different in the active treatments. The duration of action, calculated as median time with 20% or more of the maximum achieved increase in FEV1, was sustained for 9 hours and 16 minutes with salbutamol 400 micrograms, for 9 hours and 45 minutes with formoterol 6 micrograms, for 11 hours and 22 minutes with formoterol 12 micrograms, and for 11 hours and 42 minutes with formoterol 24 micrograms. CONCLUSIONS: Formoterol as a dry powder at doses of 12 micrograms and 24 micrograms produces a rapid onset of action and has a bronchodilator effect comparable with salbutamol 400 micrograms as a dry powder. The bronchodilatation was sustained for 11-12 hours. Formoterol 6 micrograms caused similar bronchodilatation but more slowly and for a shorter time. PMID- 8346491 TI - Effect of inhaled procaterol on cough receptor sensitivity to capsaicin in patients with asthma or chronic bronchitis and in normal subjects. AB - BACKGROUND: To evaluate the effect of inhaled beta 2 adrenergic agonists on the sensitivity of airway cough receptors, the effect of inhaled procaterol on cough induced by aerosolised capsaicin, a stimulant of C fibres, was studied in patients with asthma or chronic bronchitis and in normal subjects. METHOD: Eleven patients with asthma and 10 with chronic bronchitis and 14 normal subjects participated. Increasing concentrations of capsaicin solution were inhaled for 15 seconds by tidal breathing through the mouth at one minute intervals until five or more coughs were elicited, before and 30 minutes after inhalation of 20 micrograms procaterol or placebo (freon gas alone) through a metered dose inhaler. Cough threshold was defined as the lowest concentration of capsaicin that elicited five or more coughs. To evaluate the bronchodilator effect of procaterol and the bronchoconstrictor effect of inhaled capsaicin, forced expiratory volume in one second (FEV1) was measured before and one minute after a capsaicin provocation test. This test was carried out both before and 30 minutes after treatment with procaterol or placebo. RESULTS: The geometric mean value of cough threshold to capsaicin was significantly increased by procaterol and placebo in both groups of patients but not in the control subjects. The increment in the cough threshold was not significantly different between the treatments with procaterol and placebo in each group. FEV1 was significantly increased by procaterol but not by placebo in all three groups. CONCLUSIONS: Inhaled procaterol has no effect on airway cough receptor sensitivity to capsaicin. The attenuation of the cough sensitivity seen after inhalation of procaterol in patients with asthma and bronchitis may result from tachyphylaxis to capsaicin. PMID- 8346492 TI - Serum titres of Pneumocystis carinii antibody in health care workers caring for patients with AIDS. AB - BACKGROUND: Pneumocystis carinii pneumonia was thought to occur from reactivation of latent infection, but recent studies with the polymerase chain reaction have failed to detect P carinii in normal subjects. If pneumocystis pneumonia is therefore caused by new infection the source and mode of transmission of P carinii remains unknown. METHODS: Natural exposure to P carinii was detected by measuring antibodies by indirect immunofluorescence in 24 health care workers working continuously with patients with AIDS and 24 control health care workers exclusively treating elderly patients. RESULTS: P carinii antibody titres were significantly higher in the health care workers exposed to AIDS than in the control group (median titre 1:32 v 1:16 respectively). Three control subjects had no antibodies compared with none of the subjects exposed to AIDS, and 10 of the 12 highest titres came from the exposed group. CONCLUSIONS: Raised P carinii antibody titres in health care workers caring for patients with AIDS suggest that patients infected with HIV may be a potentially infectious source of P carinii for susceptible subjects. PMID- 8346493 TI - Ciliary beat frequency in transplanted lungs. AB - BACKGROUND: Patients with lung transplantation are prone to respiratory infections. Generally this is attributable to the effects of immunosuppressive drugs but mucociliary clearance has been found to be impaired in these subjects. A study was performed to determine whether this finding is accompanied by a reduction in ciliary beat frequency (CBF). METHODS: Six patients who had undergone single lung transplantation for fibrosing lung disease were investigated. CBF was measured in mucosal samples from native and transplanted bronchi by a videophotometry method. RESULTS: The CBF was reduced in the transplanted bronchi in all cases when both fastest and slowest beating cilia were examined. The fastest beating cilia on the native side had a mean (SD) CBF of 12.1 (1.3) Hz compared with 9.6 (2.0) Hz on the transplanted side. The slowest beating cilia also had reduced CBF on the transplanted side. CONCLUSION: In patients with fibrotic lung disease, CBF is reduced in transplanted bronchi in comparison with native bronchi. PMID- 8346494 TI - Percutaneous needle biopsy of the mediastinum: review of 94 procedures. AB - BACKGROUND: A number of reports of radiologically guided percutaneous biopsy of mediastinal masses have been described but techniques have varied, particularly the type of needle used. In this study mediastinal biopsies with fine aspiration needles and cutting needles have been compared, sometimes in the same patient. The results are reviewed with particular emphasis on the choice of biopsy needle and its influence on pathological diagnosis. METHODS: A retrospective review was undertaken of radiologically guided mediastinal biopsies performed between 1981 and 1991. RESULTS: Sixty fine needle aspiration biopsies (FNA) and 34 Tru-Cut biopsies of mediastinal masses were performed in 75 patients with fluoroscopic or computed tomographic guidance. Overall sensitivity and specificity in terms of diagnosis of malignant disease were 90% and 100% respectively for FNA biopsies, and 96% and 100% for Tru-Cut biopsies. Diagnostic accuracy in terms of precise diagnosis of the malignant or benign nature of a mass and its origin was 77% for FNA biopsies and 94% for Tru-Cut biopsies. For FNA biopsies sensitivity and accuracy were higher for carcinomatous lesions (96% and 88%) than for noncarcinomatous lesions (81% and 69%). The only significant complication encountered was a pneumothorax following a biopsy which required intercostal drainage. CONCLUSIONS: Radiologically guided percutaneous needle biopsy is a safe procedure which provides useful diagnostic information in the majority of cases. Fine needle aspiration techniques usually suffice for carcinomatous lesions but a cutting needle biopsy should be performed whenever possible when lymphoma, thymoma, or neural masses are suspected to obtain larger specimens for more accurate histological diagnosis. PMID- 8346495 TI - Effects of recombinant GM-CSF and IgA opsonisation on neutrophil phagocytosis of latex beads coated with P6 outer membrane protein from Haemophilus influenzae. AB - BACKGROUND: IgA is the major antibody class in mucosal secretions, yet its biological functions remain poorly understood and its role as an opsonin for neutrophils has been the subject of controversy. It has been reported that treatment of neutrophils with granulocyte-macrophage colony stimulating factor (GM-CSF) induces the cells to phagocytose particles opsonised with IgA. A study was performed to investigate the effects of GM-CSF and IgA opsonisation on the ability of human neutrophils to recognise and phagocytose latex beads coated with the P6 outer membrane protein of Haemophilus influenzae. METHODS: Human neutrophils with and without preincubation with 100 pmol/l GM-CSF, were incubated with non-opsonised P6-coated latex beads or beads opsonised with IgA purified from the blood of a bronchiectatic patient with high titres of IgA anti-P6. Phagocytosis was measured by counting internalised beads during microscopic examination. RESULTS: The phagocytosis of IgA opsonised beads by untreated neutrophils (mean (SE) 2.1 (0.43) beads/cell) was significantly greater than that of non-opsonised beads (mean (SE) 1.3 (0.30) beads/cell). Treatment of neutrophils with GM-CSF resulted in increased phagocytosis of non-opsonised beads (mean (SE) 2.1 (0.39) beads/cell) but opsonisation with IgA increased this further (mean (SE) 3.4 (0.53) beads/cell). CONCLUSIONS: Human neutrophils recognise and phagocytose non-opsonised particles coated with bacterial antigen. Antibodies of the IgA isotype opsonise for neutrophil phagocytosis of particles coated with bacterial antigen but this behaviour is enhanced, in an additive fashion, by treatment of the cells with GM-CSF. The results suggest that IgA and GM-CSF are important cofactors for neutrophil recognition and elimination of bacterial pathogens. PMID- 8346496 TI - Use of a combined oxygen and carbon dioxide transcutaneous electrode in the estimation of gas exchange during exercise. AB - BACKGROUND: Accurate and reliable measurement of gas exchange during exercise has traditionally involved arterial cannulation. Non-invasive devices to estimate arterial oxygen (O2) and carbon dioxide (CO2) tensions are now available. A method has been devised and evaluated for measuring gas exchange during exercise with a combined transcutaneous O2 and CO2 electrode. METHODS: Symptom limited exercise tests were carried out in 24 patients reporting effort intolerance and breathlessness. Exercise testing was performed by bicycle ergometry with a specifically designed protocol involving gradual two minute workload increments. Arterial O2 and CO2 tensions were measured at rest and during exercise by direct blood sampling from an indwelling arterial cannula and a combined transcutaneous electrode heated to 45 degrees C. The transcutaneous system was calibrated against values obtained by direct arterial sampling before each test. RESULTS: In all tests the trend of gas exchange measured by the transcutaneous system was true to the trend measured from direct arterial sampling. In the 140 measurements the mean difference between the O2 tensions estimated by direct sampling and the transcutaneous method was 0.08 kPa (0.62 mm Hg, limits of agreement 4.42 and 3.38 mm Hg). The mean difference between the methods for CO2 was 0.02 kPa (0.22 mm Hg, limits of agreement 2.20 and -1.70 mm Hg). There was no morbidity associated with the use of the transcutaneous electrode heated to 45 degrees C. CONCLUSIONS: A combined transcutaneous O2 and CO2 electrode heated to 45 degrees C can be used to provide a reliable estimate of gas exchange during gradual incremental exercise in adults. PMID- 8346497 TI - Effect of seasonal allergic rhinitis on airway mucosal absorption of chromium-51 labelled EDTA. AB - BACKGROUND: Hyperpermeability of the airway mucosa is thought to be characteristic of allergic rhinitis and asthma. Nine subjects with seasonal rhinitis caused by birch pollen were studied and the nasal mucosal absorption of chromium-51 labelled EDTA was examined both in an asymptomatic period before the season and late into the season when significant allergic rhinitis symptoms were present. METHODS: A nasal pool device was used to keep a concentration of the absorption tracer in contact with a larger part of the mucosa of the ipsilateral nasal cavity. Absorption was allowed for 15 minutes and measured as the radioactivity appearing in the 24 hour urine sample. RESULTS: The nasal absorption of 51Cr-EDTA in subjects with seasonal allergic rhinitis was less during active disease than before the season. CONCLUSIONS: An airway epithelial barrier that is subject to prolonged eosinophilic inflammation may not be disrupted but may rather increase its functional tightness. PMID- 8346498 TI - Effects of nicotine on the human nasal mucosa. AB - BACKGROUND: Topical application of nicotine and stimulation of tachykinin containing sensory nerves have been shown to produce mucosal exudation of plasma and derangement of the epithelial lining in guinea pig and rat airways. If this occurred in man these effects might contribute to the pathogenesis of airway disease. This study, performed in healthy volunteers without atopy, examined whether nicotine affects the plasma exudation response and the mucosal absorption permeability of the human nasal airway. METHODS: The acute effects of increasing topical doses of nicotine (0.08-2.0 mg) were examined (n = 8) on nasal symptoms (pain), mucosal exudation of plasma (albumin), mucosal secretion of mucin (fucose), and mucosal exudative responsiveness (histamine induced mucosal exudation of albumin). A separate placebo controlled study was carried out to determine whether frequent applications of the high dose of nicotine (2.0 mg given eight times daily for nine days) had any deleterious effects on the airway mucosa detectable as altered responses to histamine challenge. Both mucosal exudation of plasma (n = 12) and mucosal absorption of chromium-51 labelled EDTA (n = 8) were thus examined in nasal airways exposed to both nicotine and histamine. RESULTS: Nicotine caused nasal pain and produced dose dependent mucosal secretion of fucose but failed to produce any mucosal exudation of albumin. The exudative responsiveness to histamine was, indeed, decreased when the challenge was performed immediately after administration of acute doses of nicotine, whereas the responsiveness was unaffected when histamine challenges were carried out during prolonged treatment with nicotine. The nasal mucosal absorption of 51Cr-EDTA in the presence of histamine did not differ between subjects receiving either placebo or nicotine treatment for nine days. CONCLUSIONS: The results indicate that nicotine applied to the human airway mucosa produces pain and secretion of mucin, but inflammatory changes such as mucosal exudation of plasma and epithelial disruption may not be produced. Neurogenic inflammatory responses, which are so readily produced in guinea pig and rat airways, may not occur in human airways. PMID- 8346500 TI - Age related increase in the intra-alveolar macrophage population of non-smokers. AB - The alveolar macrophage population is higher in smokers than in non-smokers. An age related increase in the alveolar macrophage number in the lungs of non smokers has been found, whether expressed per unit lung volume or per unit lung surface area. PMID- 8346499 TI - Cytokines. 1. Overview. PMID- 8346501 TI - Mucosa associated lymphoma of the lung. AB - Two cases of mucosa associated lymphoma (pseudolymphoma) of the lung are described which highlight the varied clinical and radiological features of this rare pulmonary condition. Following chemotherapy with prednisolone and chlorambucil, both patients are disease free three years later. PMID- 8346502 TI - Culture of Mycobacterium kansasii in the blood of an HIV negative patient. AB - A 23 year old man with a congenital myelodysplastic disorder and fibrosing lung disease received treatment with prednisolone. After nine months his condition deteriorated and Mycobacterium kansasii was isolated from blood cultures and lymph node biopsy specimens. He responded to antituberculous treatment. M kansasii has not previously been isolated from the blood stream of HIV negative patients. PMID- 8346503 TI - Lung abscess: a neglected cause of life threatening haemoptysis. AB - Three cases who presented with life threatening haemoptysis are reported, all of whom required surgery to control the bleeding. In all three patients chronic lung abscess was responsible for the haemoptysis. Even in the absence of typical clinical or radiographic features of an abscess this diagnosis should be considered in any patient presenting with life threatening haemoptysis. PMID- 8346504 TI - Mitral valve replacement for an annular submitral aneurysm of the left ventricle. AB - Successful surgical repair of an annular submitral aneurysm of the left ventricle in two patients is described. In both cases the diagnosis was made at surgery and they were treated successfully by transatrial closure of the aneurysm with Teflon felted sutures and mitral valve replacement. This is the first report of the use of mitral valve replacement for this condition. PMID- 8346505 TI - Cohabiting with domestic mites. PMID- 8346506 TI - Tuberculin positive children. PMID- 8346507 TI - Estimating age, sex and period specific constant tar cigarette consumption in the UK. PMID- 8346508 TI - Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases. PMID- 8346509 TI - [Serological study of the occurrence of L. hardjo in sheep in The Netherlands]. AB - Sheep (3918) from 137 farms in the regions of North-, West- and Mid-Netherlands and Gelderland were serologically investigated for the presence of antibodies against Leptospira hardjo. Antibodies were detected in 3.3% of the sheep. There were large regional differences with respect to both the percentage of positive sheep and the percentage of positive flocks. All sera from sheep in Gelderland were negative. In West- en Mid-Netherlands there were 0.9 and 6.5% positive sera, respectively, and 19.4 and 32.7% positive flocks. The percentage of positive sheep per positive flocks varied from 1 tot 51.6. Serological positive sheep were from farms with and without cattle. On farms with cattle, there was no clear relationship between serologically sheep and the presence of hardjo antibodies in cattle. It thus seems plausible that sheep can be infected with hardjo independently of cattle. PMID- 8346512 TI - [Keeping pigs after the turn of the century; a healthy look forward and only when 'pigs will fly']. PMID- 8346510 TI - [A case of oleander poisoning in a cat]. AB - This case history describes clinical symptoms and pathological changes in a cat that are consistent with those of oleander intoxication. The clinical symptoms were characterized by vomiting, diarrhoea, and ventricular extrasystoles. On post mortem examination focal degeneration and necrosis of the myocardium was seen, as well as haemorrhage of myocardium and wall of the gastrointestinal tract. An overview is given of the literature on the diagnosis, pathogenesis, and treatment of oleander intoxication in different animals and in humans. PMID- 8346511 TI - [Analgesics; the use of aspirin in dogs; effects of tablet type and food intake on plasma salicylate level]. AB - Administration of acetylsalicylic acid (aspirin) in the dog may cause gastric mucosal damage. Enteric-coated tablets protect the canine stomach during oral aspirin medication. A therapeutic plasma salicylate concentration can be attained using enteric-coated aspirin tablets at a dosage of 25 mg/kg TID. In a series 4 of experiments using adult beagle and large mixed breed dogs and two types enteric-coated tablets, the influence of food intake on the plasma salicylate concentration was studied. Tablets were administered with 8h intervals and food intake was either once daily or three time daily with 8h intervals. Plasma salicylate concentrations were also studied during fasting. It is concluded that, when using enteric-coated tablets, the plasma salicylate concentration in the dog after oral medication is strongly influenced by the aspirin dosage, the tablet type and the feeding pattern. Large enteric-coated tablets may accumulate in the stomach over several days and are not suitable for use in the dog. The gastric accumulation is caused by the enteric-coating of the large tablets and not by the aspirin medication. PMID- 8346514 TI - [Specific gravity of urine]. PMID- 8346513 TI - [What is a rodent ulcer?]. PMID- 8346515 TI - [Low selenium status]. PMID- 8346516 TI - [United Europe and veterinary professional level. Lecture on the occasion of the celebration of the promotion of the veterinary faculty at Munich on February 26, 1993]. PMID- 8346517 TI - [The use of zinc oxide in piglets]. PMID- 8346518 TI - [The clinical case. Mixed breed bitch, 8 years old]. PMID- 8346519 TI - [An unusual combination of different organ and skeletal abnormalities in a black and white calf]. AB - This is a case report of a rare malformation in a calf: duplicitas posterior incompleta in combination with multiple malformations (diphallia, polymelia, polydactylism, lack of the bony floor of the pelvis, asymmetrical pelvis, asymmetrical sacral and coccygeal vertebrae, unilateral hypoplasia of the kidneys). A detailed description of the clinical and pathological findings is presented. PMID- 8346520 TI - [Oral aspergillosis in a goat--a stomatologic problem. Case report]. AB - This report describes a case of chronic and granulomatous proliferation in the lower jaw of a six-year-old female Saanen goat due to Aspergillae spp. Within the granulomatous lesion, foreign body and Langhans type giant cells were present in addition to the common granuloma components, such as lymphocytes, epithelioid cells and fibroblasts. Hyphae with a configuration typical of Aspergillae spp. could be demonstrated within the lesions by the use of special stains. The prognosis of this disease in the advanced stage is poor. PMID- 8346521 TI - [The forecasting of the time of calving using a rapid progesterone test]. AB - The rectal temperature and any alterations in eight different external signs of parturition were investigated twice daily in 22 "Deutsche Schwarzbunte" cows during the last 10 days of gestation. There was great variation in the externally detectable signs of parturition during the preparatory stages and short before labour. During the same time period, plasma progesterone and total oestrogens were determined using radioimmunology. From 60 hours to 12 hours prior to calving the progesterone levels fell rapidly to 0.77 +/- 0.22 ng/ml. Additionally, the plasma progesterone was determined semi-quantitatively in 31 cows using a rapid progesterone assay in order to predict the commencement of parturition within 36 hours. This allowed a more objective and reliable assessment of calving time than the evaluation of external signs of labour. PMID- 8346522 TI - [Observations on the maturity of stillborn calves]. AB - Organ weight and trace element analyses were performed on 75 stillborn calves from the same dairy cow herd. The elements Fe, Mn, Zn and Cu were measured in the livers of 66 of the calves. The calves ranged in age from 259 to 299 days of gestation, and in weight from 18 to 58 kg. Based on the quotients of organ and other body parts, stage of growth of the humerus and age, the animals were grouped as either preterm (P), term but light (TL), and term with appropriate weight (TA) calves. In P group calves the heart, lungs, liver, kidneys, thymus, spleen and thyroid glands were relatively heavy. In the TL group calves the brain, heart, lungs and thyroid glands were relatively heavy whereas the spleen and thymus were comparatively light. The liver Fe and Zn values were lower in this group than in the other 2 groups. PMID- 8346523 TI - [Analysis of the obstetrical situation in swine from the clinical point of view]. AB - In a study including 477 parturitions in sows the obstetrical situation of this species is analyzed from the clinical point of view. Obstetrical interventions before consulting the veterinary clinics led to partly severe lesions of soft tissues of the genital tract in 35.5% of all primiparous and in 12.6% of all pluriparous sows. So 3.1% of all obstetrical patients had to be slaughtered due to the enormous perforating lesions in vestibular-vaginal-cervical parts of the genital tract. In 71 cases parturition could not be completed because of stress, insufficiency of the cardiovascular system or economic reasons. In general, 76% of parturitions came to an end conservatively and 24% by caesarean section. In older sows the relation was 88% vs. 13%. During the recent years the loosing-rate by completed parturition could be reduced to 3.4% after conservative obstetrical intervention and to 20.6% after caesarean section in preinjured sows by compensation of the respiratory and metabolic acidosis, stabilizing of the cardiovascular system and the supply of warmth. Possibilities to diminish total losses are discusses, concerning the large number of animals with injuries due to inappropriate conservative obstetrics as well as the intensification of intra- and postoperative supportive therapy. PMID- 8346524 TI - [The occurrence of Chlamydia psittaci infections in raptors from wildlife preserves]. AB - 152 free-living raptors found in the area around Munich, Germany, were investigated for possible Chlamydia psittaci infections. Chlamydia psittaci was detected in 13.2% of these birds of prey (Strigiformes, Falconiformes and Accipitriformes) by examination of cloacal swabs with an antigen ELISA (IDEIA Chlamydia test kit). Chlamydia psittaci antibodies could be demonstrated in 85.1% of 121 birds by a Chlamydia antibody ELISA (Chlamydia-psittaci-AK-EIA). 29.7% of the samples investigated were positive, 55.4% showed strong positive reactions. The birds showed neither clinical nor pathological signs of chlamydial infections. The specificity and sensitivity of the Chlamydia antibody ELISA, as determined using positive sera and epidemiological criteria are discussed. Antigen ELISA and the cell culture method showed a consistency of 94%. The results and their consequences for diagnostic procedures and state regulations are discussed. PMID- 8346525 TI - [Bilateral blindness after injury in a riding horse]. AB - Bilateral blindness was diagnosed in a 5-year-old Hanoverian gelding presented for evaluation of a corneal opacity in one eye. About 12 months prior to the examination, the gelding had fallen head over, hitting his head and the cornea. Clinical and electroretinographic findings as well as pathohistologic and ultrastructural lesions of both eyes including the optic nerves are presented. Ophthalmoscopically visible pigment disruption of the non-tapetal fundus adjacent to the optic discs correlated morphologically with foci of degeneration and atrophy of the retina, whereas ophthalmoscopically visible accumulation of pigment was morphologically characterized by hypertrophy of the pigment epithelium, increased intracellular pigment accumulation and by migration of pigment cells into the inner lamina of the retina. Severe atrophy of the retinal neuronal layer was linked to traumatic optic nerve degeneration. PMID- 8346526 TI - [Foal diseases and foal loss]. AB - An investigation was carried out upon occurrence and course of infectious and non infectious diseases as well as the mortality in foals born and raised at the State Stud Marbach/Lauter between 1982 and 1991. The foals have been investigated from birth to weaning, they consisted of 177 Thoroughbred Arabians and 285 German Warmblood foals (total 462 foals). The diseases were divided into pre-, peri- and postnatal according to their known or assumed cause and onset. There was a preponderance of prenatal diseases (11.25%) whereas the perinatal rate was 1.30% and the postnatal rate of diseases was 8.66%. The rate of infectious diseases increased from the pre- to the postnatal period of life. A comparison between the two breeds showed that 9% of the Arabian foals suffered from infectious diseases whereas only 4.9% of the Warmblood foals were similarly affected. This is probably linked to the lower level of colostral immunoglobulins in the Arab herd, as previously shown by us. The measurement of mare colostral and foal serum IgG as well as the paramunisation of neonatal and weaned foals are important factors in the prevention of infectious diseases. PMID- 8346527 TI - [Symptoms: anorexia and emaciation]. AB - Anorexia and emaciation are symptoms which can be found in many diseases either singly or in combination with other unspecific clinical signs such as diarrhea and vomiting. Therefore accurately assessing the medical history, performing a thorough clinical examination and carrying out laboratory tests are all necessary steps in establishing a diagnosis. Further specific examinations such as radiography, ultrasonography or endoscopy may also have to be performed. Since anorexia and emaciation can result in severe consequences for the organism, establishing a definitive diagnosis is important to enable the appropriate therapy to be applied without delay. PMID- 8346528 TI - [Significance of bone marrow cytology in the diagnosis of leukosis in dogs]. AB - In the differential diagnosis of neoplastic diseases of blood cells or their precursors, cytological examination of bone marrow is a valuable diagnostic tool. Depending on the expected cell type, an aspiration followed by clinical cytological examination, or a biopsy followed by histopathological examination is indicated. In all unclear cases of cytopenia, if blood parasites or a lymphatic leukemia without tumors are suspected or in myeloproliferative diseases, bone marrow cytology can provide the diagnosis. If the aspiration of bone marrow is not possible in spite of correct technique (punctiosicca), myelofibrosis must be suspected. The diagnosis is confirmed by bone marrow biopsy. In the most common form of leukemia in dogs, the lymphosarcomatosis, a bone marrow biopsy can be helpful in assessment of the prognosis. PMID- 8346529 TI - [Stabilization of tracheal collapse in dogs]. AB - A surgical technique to stabilize collapsing trachea in dogs by implanting strips of porous polyethylene around the trachea is reported. PMID- 8346530 TI - [Feline ocular melanoma. Clinical and pathologico-anatomic findings in 37 cases]. AB - The clinical and pathological findings of 37 feline ocular melanomas are described. The majority of the tumors examined were diffuse iris-ciliary body melanomas of epithelioid and pleomorphic (anaplastic) cell type with numerous mitotic figures. The majority of the tumors showed invasion of the anterior sclera. Metastases were found in three cases predominantly in the abdominal viscera (liver). The clinical diagnostics as well as the differential diagnosis, therapy and prognosis of feline uveal melanoma are presented. The causal pathogenesis is discussed comparatively. PMID- 8346531 TI - [Functional and applied anatomy of the shoulder joint of the domestic cat]. AB - The freedom of movement of the feline shoulder joint corresponds to that of a ball-and-socket joint, although the humeral head is not ball-shaped. The profiles of the humeral head and glenoid fossa were analysed with respect to their lines of movement in three planes of motion. The incongruity of the joint surfaces allows the variety of movements. Of clinical relevance are the description of a shoulder joint injection site and of the extent of joint movement in degrees. PMID- 8346532 TI - [Monkey AIDS, a new zoonosis?]. AB - Monkeys may carry dangerous infectious diseases. Several studies have demonstrated frequent lentivirus infections in different monkey species. This report describes virological and epizootiological aspects of and the diagnostic procedure for the evaluation of SIV infections in African green monkeys. Recommendations for the prevention of transmission of SIV to humans are discussed. PMID- 8346533 TI - The toxicologic interactions resulting from inhalation of carbon black and acrolein on pulmonary antibacterial and antiviral defenses. AB - The goal of this study was to investigate whether coexposures to carbon black and acrolein result in a toxicologic interaction having effects on lung defenses against infectious agents. This aim was accomplished through in vivo studies with inhalation challenges of infectious agents that probe the functional integrity of the multicomponent system that comprises the integrated defenses of the lungs. Staphylococcus aureus was used for the alveolar macrophage (AM) surveillance phagocytic system, Proteus mirabilis for the dual phagocytic system composed of AMs and inflammatory polymorphonuclear leukocytes (PMNs), Listeria monocytogenes for the lymphokine-mediated arm of the acquired cellular immune response, and influenza A virus for the cytotoxic T-cell-mediated effector mechanism of cellular immunity. Exposures of Swiss mice to target concentrations of 10 mg/m3 of carbon black and 2.5 ppm acrolein for 4 hr/day for 4 days suppressed the intrapulmonary killing of S. aureus a day after exposure with a return to control levels by Day 7. In contrast, the coexposure enhanced the intrapulmonary killing of P. mirabilis which correlated with a significant increase in accessory phagocytic PMNs recovered from the lungs. Combined exposure to carbon black and acrolein also resulted in impaired elimination of L. monocytogenes and influenza A virus from the lungs. Neither exposure to carbon black alone nor exposure to acrolein alone had any effect on the functional integrity of lung defenses against the four infectious agents. These data demonstrate the effects of the toxicologic interaction of coexposures to an inert particle and acrolein on innate and acquired defenses of the lungs. The mechanism for the enhanced biologic effect may be that the carbon black particle acts as a carrier mechanism for acrolein to the deep lung. PMID- 8346534 TI - Transport and toxicity of methylmercury along the proximal tubule of the rabbit. AB - Toxicity and transport of methylmercury were studied in isolated perfused S1, S2, and S3 segments of the renal proximal tubule of the rabbit. Methylmercury (II) chloride, ranging from 1 nM-1 mM, was perfused through the lumen of the three segments for up to 60 min. Lumen-to-bath transport of methylmercury was studied when the concentration of methylmercury in the perfusing solution was 18.4 microM. S1 segments of the proximal tubule were most vulnerable to the toxic effects of methylmercury. Cellular swelling and blebbing occurred when the concentration of methylmercury in the perfusate was as low as 1 nM. In the S2 and S3 segments, morphologically discernable cellular injury did not occur until the concentration of methylmercury in the perfusate was greater than 100 nM. Due to severe cellular injury and luminal occlusion, transport data could not be obtained from S1 segments. However, transport could be measured in both S2 and S3 segments. Methylmercury (18.4 microM) disappeared from the luminal fluid across the luminal membrane (JD) very rapidly in both segments. The rate was so rapid that about 80% of the methylmercury that entered the luminal fluid was abstracted. Interestingly, the rate at which mercury appeared in the bathing solution (JA) was statistically equivalent to the JD. Since the predicted leak of methylmercury was very low, most of the JA represented actual transepithelial flux of methylmercury. When 80 microM glutathione (GSH) was added to the perfusate along with 18.4 microM methylmercury, the JD was decreased significantly in both S2 and S3 segments. Moreover, the addition of 80 microM GSH caused cellular injury to be exacerbated in the S3 segments. In conclusion, there are differences in the toxicity of methylmercury along the three segments of the proximal tubule when the methylmercury is delivered to the lumen of the segments in a simple electrolyte solution. Methylmercury is very avidly transported across the tubular epithelium in S2 and S3 segments of the proximal tubule. In addition, when 80 microM GSH is added to the perfusate, the toxicity and transport of methylmercury are modified. PMID- 8346535 TI - Alveolar and airway cell kinetics in the lungs of rats exposed to nitrogen dioxide, ozone, and a combination of the two gases. AB - Rats carrying minipumps filled with 5-bromo-2'deoxyuridine were exposed to ozone, NO2, or a mixture of the two gases using four different protocols: (A) ozone 0.2 ppm, NO2 3.6 ppm, or their mixture for 24 hr a day; (B) ozone 0.2 ppm, NO2 7.2 ppm, or their mixture for 12 hr per night; (C) ozone 0.6 ppm, NO2 10.8 ppm, or their mixture for 8 hr per night; and (D) ozone 0.8 ppm, NO2 14.4 ppm, or their mixture for 6 hr per night. After three consecutive daily exposures, the animals were returned to filtered air and killed 7 days after implantation of the minipump. Alveolar labeling indices were comparable to control values except in the group of animals exposed for 6 hr nightly to a combination of 0.8 ppm of ozone and 14.4 ppm of NO2. Labeling indices in the peripheral airways were the most sensitive exposure index since they were significantly increased over control values in all animals exposed to ozone, NO2, or a mixture of the two gases, regardless of concentration or exposure duration. Labeling indices increased with elevated dose rate, i.e., concentration of the gases in the inspired air. The response to the combined gases was greater than the calculated sum of the responses to the two individual gases for the three higher dose rates in the large airways and for the highest dose rate in the peripheral airways. The results led to the following conclusions: (1) By the criterion of analysis of cell kinetics in rat large and peripheral airways, neither ozone, NO2, nor their mixture follows Haber's law (c x t = k) over the concentration ranges studied; and (2) at the higher dose rates studied, there is a more than additive (synergistic) airway response to the combination of ozone and NO2. PMID- 8346536 TI - The genotoxic effects of arachidonic acid in V79 cells are mediated by peroxidation products. AB - Chinese hamster lung fibroblasts (V79 cells) were exposed to 2, 20, 160, and 200 microM arachidonic acid (AA). At 20 microM, a stimulatory effect on cell growth was observed, while at 200 microM, an inhibitory effect was found. AA at 160 and 200 microM induced a 10- to 12-fold increase of 6-thioguanine-resistant mutants in V79 cells, whereas increased alkaline labile sites on DNA were consistently produced only with 200 microM treatment doses. The induction of alkaline labile lesions was partially inhibited in the presence of an antioxidant NDGA. [3H]AA metabolism in cells was examined by HPLC analysis following reductive transmethylation of the cell lipid extracts. Two fractions corresponding to [3H]AA-derived peroxidation products were identified by HPLC-radiochromatography and analyzed by mass spectrometry. Quantitative evaluation of the radioactivity associated with these peaks revealed an increase in [3H]AA peroxidation products when cells were exposed to increasing amounts of AA. The AA-dependent stimulation of lipid peroxidation product formation was partially inhibited when cells were treated in the presence of NDGA. The results provide evidence that substantially enlarged AA pools in cells may induce genotoxic effects mediated through increased endogenous lipid peroxidation products. PMID- 8346537 TI - Cadmium uptake by primary cultures of rat renal cortical epithelial cells: influence of cell density and other metal ions. AB - The uptake and accumulation of 1-5 microM cadmium (Cd) was studied in primary cultures of rat renal cortical epithelial cells under protein-free conditions at 4 or 37 degrees C for up to 30 min. The cells were isolated from female rats by collagenase digestion and cultured for 3-7 days. Confluency of the culture, monitored morphologically as well as by total protein content, was achieved on Day 5. Cd accumulation at 1 microM concentration demonstrated an inverse relationship to the cell density; the Cd level in Day 5 culture was only 45% of that in Day 3 culture. In subconfluent cultures (Days 3 and 4) the Cd accumulation was temperature sensitive; on Day 3 the cells accumulated one-third less Cd at 4 degrees C than at 37 degrees C. In comparison, the confluent cells (Day 5) had the same Cd accumulation regardless of the incubation temperature. In these cells, preincubation with cyanide also had no significant effect on Cd accumulation, implying a lack of energy requirement for Cd uptake. As the transport of Cd may involve processes that exist for the essential metal ions, the effect of 30 microM zinc (Zn) and copper (Cu) on the accumulation of 1 microM Cd was studied in Day 5 cultures. Coincubation with Zn caused a 16% reduction in Cd levels at 37 degrees C and even greater reduction (44% of control) at 4 degrees C. Similarly, Cu inhibited Cd accumulation by 26 and 45% at 37 and 4 degrees C, respectively, as compared to the temperature-matched controls. The Vmax for the initial Cd uptake (1 min) was 125 pmol/mg protein/min and the Km was 7 microM. Both Zn and Cu exhibited competitive inhibition kinetics and doubled the Km for Cd uptake. The Ki for Zn and Cu was 23 and 30 microM, respectively. Mercury (Hg) and lead (Pb) were also tested for their ability to affect Cd accumulation. As compared to the controls, 1 microM Hg caused an 11% reduction in Cd level at 37 degrees C. In contrast, 1 microM Pb enhanced Cd accumulation by 20%. However, neither Hg nor Pb had any significant effect on Cd accumulation at 4 degrees C. All four metals had no significant effect on the efflux of Cd from the cells. Thus, these metals affected Cd accumulation by changing its uptake rather than its efflux.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8346538 TI - Effects of the bisphosphonate, alendronate, on parturition in the rat. AB - Alendronate is a bisphosphonate which inhibits bone resorption. In female fertility studies in rats, dosages of 10 and 15 mg/kg/day produced physical signs of toxicity at parturition, including tremors, dystocia, and death in the dams and these were associated with neonatal deaths. These effects were associated with hypocalcemia in the dams but the fetuses were normocalcemic. There was no one critical period of treatment during gestation for these effects; they were instead proportional to length of treatment. Neonatal deaths were due to protracted deliveries rather than a direct effect of alendronate on the pups. Intravenous calcium supplementation (9.3 mg/dam) prevented the above-described adverse effects on dams and pups. In rats, fetal skeletal ossification is at its greatest rate in late gestation, and during this period free calcium is preferentially transported to the fetal compartment. The females meet this increased demand by calcium mobilization via increased bone resorption. We conclude that the maternotoxicity of alendronate in rats is due to the designed pharmacologic activity of this bisphosphonate; the drug prevents bone resorption and thereby denies the dam an important source of calcium at a time when fetal demand for this mineral is at its peak. The alendronate-induced hypocalcemia adversely affects parturition because uterine muscle contraction is a calcium dependent process. PMID- 8346539 TI - Metabolism and toxicity of intravenously injected yttrium chloride in rats. AB - Although radioactive yttrium (Y) has been used for medical treatment, little attention has been directed toward the toxicity of Y. We report time-course and dose-related changes in tissue distribution, subcellular localization, clearance, and acute toxicity of iv-injected yttrium chloride (YCl3) in rats. Intravenously injected Y was predominantly distributed to plasma in the blood. At doses more than 0.2 mg Y/rat, most plasma Y appears to be in colloidal material which was composed of proteins and some minerals. Electron microscopic analyses revealed that the colloidal material was taken up by phagocytic cells in the liver and spleen. The liver Y was slowly cleared with a half-time of 144 days at a dose of 1 mg Y/rat. Glutamic-oxaloacetic and glutamic-pyruvate transaminase activities in blood plasma were increased with a peak at 20 hr postinjection at a dose of 1 mg Y/rat and returned to their control values at 170 hr postinjection, indicating that iv-injected YCl3 caused acute hepatic injury. Some of the plasma Ca was translocated to the colloidal material and plasma Ca concentration was increased transiently following injection of YCl3, probably because of resorption of bone. At a dose of 1 mg Y/rat, a significant and tremendous amount of Ca was deposited in the liver (over 10-fold) and spleen (over 100-fold), while Ca concentration was only slightly increased in the lung and kidney (less than 1.5-fold). These results indicate that the liver and spleen are primary target organs of iv injected YCl3. PMID- 8346540 TI - Comparative developmental toxicity and metabolism of nitrazepam in rats and mice. AB - This study was designed to evaluate the developmental toxicity of nitrazepam (NZ) in Sprague-Dawley rats and ICR mice and to determine the metabolic factors which modulate susceptibility to the developmental effects of NZ. Rats were treated orally with a single dose of NZ at 300 mg/kg on Day 12 of gestation. Mice received one dose of 300 mg/kg NZ via gavage between Days 9 and 14 of gestation. NZ administration resulted in a significant incidence of malformations in rats, while no evidence of teratogenic action was observed in mice. Pronounced species differences in the metabolism of NZ were observed. In rats, 7 acetylaminonitrazepam (AANZ) was detected as the major metabolite in plasma and embryos, whereas in mice, only small amounts of this product were found. The rate of N-acetylation of 7-aminonitrazepam (ANZ) to AANZ was 8.5-fold greater in rat liver cytosol than that in mouse liver cytosol. In contrast, the rate of deacetylation of AANZ to ANZ was 9-fold greater in mouse liver microsomes than that in rat liver microsomes. The developmental effects of authentic metabolites of NZ were studied in the two species. A single oral administration of 300 mg/kg ANZ to pregnant animals produced a significant incidence of malformations in rats, but not in mice. On the other hand, AANZ was teratogenic in both species. These results suggest that the difference in the susceptibility to NZ-induced teratogenicity between rats and mice may be related to differences in the levels of N-acetyltransferase and deacetylase, and that AANZ may be involved in the teratogenic mechanism. PMID- 8346541 TI - Pharmacokinetics of 2-methoxyethanol and 2-methoxyacetic acid in the pregnant mouse: a physiologically based mathematical model. AB - A physiologically based pharmacokinetic (PBPK) model was created to describe the disposition of 2-methoxyethanol (2-ME) and its teratogenic metabolite, 2 methoxyacetic acid (2-MAA), in the pregnant CD-1 mouse. The model's foundation is a mathematical description of the physiological changes that occur during gestation (O'Flaherty et al., Toxicol. Appl. Pharmacol. 112, 245-256, 1992). The PBPK model was developed and validated with data collected on Gestation Day (GD) 11. Absorption, distribution, and oxidation of 2-ME to 2-MAA and ethylene glycol (EG) were simulated. Flow-limited disposition of 2-ME in maternal tissues was described using in vitro-determined tissue partition coefficients (PCs). The maximum velocity (Vmax) of 2-ME oxidation to 2-MAA was calculated from literature based in vitro data. Vmax for EG formation, and Michaelis constants for 2-MAA and EG pathways, were estimated from optimized simulations of plasma 2-ME and metabolite levels obtained after intravenous injection of 5-600 mg 2-ME.kg-1.2 MAA disposition and elimination in the dam were described by a nonphysiological one-compartment model, which was linked to the 2-ME model, based on the volume of distribution (0.510 liters.kg-1) and overall elimination rate constant (0.124 hr 1) calculated from iv 2-MAA plasma concentration-time courses. Transfer of 2-MAA between the placenta and conceptus was described as a diffusion-limited process to more accurately simulate the higher concentrations of 2-MAA determined in embryonic compartments compared with maternal plasma levels. Subsequent 2-MAA disposition within the embryo proper and surrounding fluid of the GD 11 conceptus was adequately described using embryo/blood (0.94) and extraembryonic fluid/blood (1.33) PCs. Extension of the PBPK model to oral and subcutaneous 2-ME administrations required optimization of first-order absorption rates; model simulations agreed closely with measured 2-ME/2-MAA levels. With refinements and further validation, the PBPK model of 2-ME/2-MAA disposition should prove helpful for extrapolation throughout gestation and between species. PMID- 8346542 TI - Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat. AB - For certain inhaled air pollutants, such as reactive, water soluble gases, the distribution of nasal lesions observed in F344 rats may be closely related to regional gas uptake patterns in the nose. These uptake patterns can be influenced by the currents of air flowing through the upper respiratory tract during the breathing cycle. Since data on respiratory tract lesions in F344 rats are extrapolated to humans to make predictions of risk to human health, a better understanding of the factors affecting these responses is needed. To assess potential effects of nasal airflow on lesion location and severity, a methodology was developed for creation of computer simulations of steady-state airflow and gas transport using a three-dimensional finite element grid reconstructed from serial step-sections of the nasal passages of a male F344 rat. Simulations on a supercomputer used the computational fluid dynamics package FIDAP (FDI, Evanston, IL). Distinct streams of bulk flow evident in the simulations matched inspiratory streams reported for the F344 rat. Moreover, simulated regional flow velocities matched measured velocities in concurrent laboratory experiments with a hollow nasal mold. Computer-predicted flows were used in simulations of gas transport to nasal passage walls, with formaldehyde as a test case. Results from the uptake simulations were compared with the reported distribution of formaldehyde-induced nasal lesions observed in the F344 rat, and indicated that airflow-driven uptake patterns probably play an important role in determining the location of certain nasal lesions induced by formaldehyde. This work demonstrated the feasibility of applying computational fluid dynamics to airflow-driven dosimetry of inhaled chemicals in the upper respiratory tract. PMID- 8346543 TI - Automated counting of nuclei in series of conventional liver sections to differentiate hypertrophy and hyperplasia. AB - A method based on image analysis and applicable in pharmacology and toxicology is described that has been designed to meet the statistical requirements for the determination of liver hypertrophy or hyperplasia. An algorithm has been developed to detect and count fluorescent nuclei in Feulgen-stained liver sections (12,500 to 25,000 nuclei or 170 to 350 fields of observation per section within 2-4 hr) by means of fully automatic image analysis with the Leitz Texture Analysis System (TAS) (up to 23 sections in series on the microscope stage). The applicability of this method to conventionally derived, formaldehyde-fixed, tissue sections has been tested on 3-microns sections cut from archived paraplast blocks of already diagnosed materials. Alterations in the liver induced by eight different compounds administered perorally for 28 days to rats have been studied. The morphometric results were found to be specific for a given compound and revealed reproducible and statistically significant dose dependencies of hypertrophy or hyperplasia, or both. Increased frequencies of mitotic figures observed by eye correlated reasonably well with the morphometrically determined hyperplasia, but many hyperplastic livers revealed no mitotic figures. By contrast, the histological diagnoses of an increased degree of hypertrophy were only poorly correlated with the morphometric determinations and, in many instances, were made in livers showing no decrease in the frequency of nuclei. On the other hand, the results from electron microscopy agreed well with the corresponding morphometric analyses: in cases with predominant hypertrophy the proliferation of the smooth endoplasmic reticulum was distinct or striking, or the peroxisomes were altered and increased in number, whereas no obvious ultrastructural changes were seen in cases of morphometrically exclusive hyperplasia. PMID- 8346544 TI - Influence of the formamidine pesticide chlordimeform on ovulation in the female hamster: dissociable shifts in the luteinizing hormone surge and oocyte release. AB - The formamidine pesticide chlordimeform (CDF) has been found to interfere with the hormonal control of ovulation in the rat by a presumptive disruption in the catecholaminergic regulation of the midcycle surge of luteinizing hormone (LH). While the brain hypothalamic mechanisms underlying generation of the hamster surge have not been as well-defined, there is evidence for an adrenergic component. The present experiments were designed to investigate the effects of CDF on ovulation in the golden hamster and whether any observed alterations are associated with differences in the appearance of the surge. Intraperitoneal CDF injections (0, 75, 150, or 200 mg/kg) at 1400 hr on proestrus caused a dose related reduction in oocytes retrieved at 0700 hr on the day of estrus. Additional experiments demonstrated that this effect was due to a delay in ovulation and not a decrease in the complement of oocytes released. Doses of 150 or 200 mg/kg at 1100 hr or 200 mg/kg at 1600 hr were without a comparable ovulatory effect. Characterization of the LH surge indicated that there was a dose-related delay, but that this effect was not sufficient to account for the delay in ovulation. Animals dosed at 1100 hr (150 or 200 mg/kg) exhibited shifts in the surge identical to those animals injected at 1400 hr, but did not show any such detectable effects on the time of oocyte release. CDF administered at 1100 or 1400 hr also caused alterations in serum estradiol and progesterone, even at a relatively low dose of 37.5 mg/kg. The results indicate that CDF given at a time just prior to the preovulatory rise in LH is able to impede ovulation in the hamster by possibly influencing some ovulatory event(s) triggered by the surge. Also, the ability of CDF to alter the timing of LH release is consistent with catecholaminergic participation in the generation of the gonadotropin signal stimulating the final events leading to ovulation. Under the present conditions, this perturbation can be characterized as a delay in the LH trigger, rather than a blockade. PMID- 8346545 TI - Mechanism of trichloroethylene-induced elevation of individual serum bile acids. I. Correlation of trichloroethylene concentrations to bile acids in rat serum. AB - The temporal relationship between trichloroethylene (TRI) and individual serum bile acids (SBA) has been investigated to gain insight into the mechanism of solvent-induced increases in SBA. Male Sprague-Dawley rats were treated with 1 mmol/kg TRI in corn oil, while control rats received only corn oil. Blood samples were collected from the abdominal aorta at 2, 4, 8, and 16 hr after dosing. Individual SBA were determined by high-performance liquid chromatography (HPLC). Liver and blood concentrations of TRI and one of its metabolites, trichloroethanol (TCEOH), were determined by gas chromatography. SBA levels reached their peak at 4 hr and returned to control levels by 16 hr. There was a relationship between SBA levels and TRI concentrations, which were also at their peak 4 hr after dosing. By 16 hr the levels were undetectable. However, peak blood concentrations of TCEOH were reached 8 hr after dosing, and remained high at 16 hr. Cholic acid and taurocholic acid showed the highest levels of bile acids. Some other bile acids were also elevated, including deoxycholic acid, taurodeoxycholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and taurochenodeoxycholic acid. Determination of total bile acids in serum using an enzymatic/colorimetric method showed a similar pattern of response to that obtained with the HPLC analysis. The data are consistent with TRI having a rapid and specific effect on SBA levels by a mechanism other than liver cell damage. PMID- 8346546 TI - Mechanism of trichloroethylene-induced elevation of individual serum bile acids. II. In vitro and in vivo interference by trichloroethylene with bile acid transport in isolated rat hepatocytes. AB - The effects of trichloroethylene (TRI) on bile acid transport in isolated rat hepatocytes have been studied using doses ranging from 0.5 to 4.0 microliters/flask and a 20-min equilibration period. It was found that TRI caused a dose-related suppression of initial rates of uptake of cholic acid (CA) and taurocholic acid (TC) with no significant effect on enzyme leakage and intracellular potassium ion contents. Accumulation over 30 min for each of those two bile acids was also inhibited. A noncompetitive inhibition of bile acid uptake was shown as indicated by a decrease in maximum velocity (Vmax) and unchanged Michaelis constant (Km). Thirty minutes after cessation of TRI exposure in vitro the uptake of bile acids had gradually returned to normal levels. No significant interference of efflux was found in cells preloaded with either CA or TC. After dosing rats with 1 mmol/kg TRI in vivo the inhibition of uptake of CA and TC by subsequently isolated hepatocytes was not detected until 4 hr. By 16 hr uptake had returned to normal. The accumulation of bile acids was also suppressed at 4 and 8 hr. The inhibition of uptake after in vivo treatment was also noncompetitive. The data are consistent with the reversible increase of serum bile acids (SBA) in experimental animals after exposure to TRI. Furthermore, they support the contention that it is an interference with bile acid uptake, rather than actual cell damage, that is responsible for TRI-induced increases in SBA. Thus, the changes in SBA seem to be the result of interference with a physiological process rather than an event associated with significant pathological consequences. PMID- 8346547 TI - Epithelia hyperplasia in the renal papilla and pelvis but not the urinary bladder of male F344 rats associated with dietary sodium phosphates after uracil exposure. AB - Effects of the bladder tumor promoter Na3PO4 and the non-bladder-tumor promoter NaH2PO4 on development of hyperplastic lesions of urinary bladder and renal papilla/pelvis were investigated after exposure of male F344 rats to the nongenotoxic carcinogen uracil. Animals were administered with 3.0% uracil in the diet for 4 weeks and thereafter fed 3.0% Na3PO4 or 3.0% NaH2PO4 for 32 weeks. No enhancing effect of either phosphate salt on uracil-induced proliferative lesions of urinary bladder was observed. However, the sequential treatments gave rise to enhanced development of hyperplastic lesions in the renal papilla/pelvis compared to the case with uracil alone. In addition, a small number of renal pelvic papillomas were observed in the group given Na3PO4 after uracil. These phosphate salts also induced nephrocalcinosis in the papilla/pelvis concomitant with development of renal hyperplastic lesions in this location. A sequential study revealed calculus formation and proliferative lesions in both the urinary bladder and renal papilla/pelvis after 4 weeks dietary application of uracil. After cessation, calculi disappeared and the majority of hyperplastic lesions regressed, consistent with a decrease in DNA synthesis levels. Persistence of uracil-induced epithelial hyperplasia in renal papilla/pelvis under the influence of phosphate salts might have been directly due to chronic stimulation by nephrocalcinosis in these sites. PMID- 8346548 TI - Disposition of polycyclic aromatic hydrocarbons in the respiratory tract of the beagle dog. I. The alveolar region. AB - Clearance of polycyclic aromatic hydrocarbons (PAHs) from the respiratory tract follows a biphasic pattern, with a rapid clearance of most of the PAH followed by a slow clearance of a small fraction. In previously published models, it was predicted that the rapid phase represents clearance through the thin epithelial barriers in the alveoli, the slow clearance is through the thicker epithelium of the airways, and the rate of clearance from either region will be slowed if the PAH has a high degree of lipophilicity. The objective of this first study in a series of three was to validate model predictions for rates of alveolar clearance of PAHs of different lipophilicities. A new method was developed to expose dogs to a bolus of aerosolized crystals of either benzo[a]pyrene (BaP) or phenanthrene (Phe) in a single breath. A bolus of PAH crystals was formed by condensation from a heated vapor and was injected into the pulmonary region. The bloodborne clearance of the PAHs was monitored by repeatedly sampling blood through catheters in the ascending aorta and the right atrium of the dog. Half of the Phe and the BaP cleared within 1 min and 2.4 min, respectively. The data indicated that the clearance of the highly lipophilic BaP was limited by diffusion of the PAH through the alveolar septa, while clearance of the moderately lipophilic Phe was limited mostly by the rate of perfusion of the blood. The results indicate that inhaled PAHs of sufficient lipophilicity to limit diffusion through cells have a greater potential for toxicity to the lung than less lipophilic PAHs. Because of thicker epithelia, bronchi should be at greater risk than the alveoli for PAH-induced toxicity exerted at the portal of entry. PMID- 8346549 TI - Disposition of polycyclic aromatic hydrocarbons in the respiratory tract of the beagle dog. II. The conducting airways. AB - Physiological models have predicted that the lipophilicity of solutes such as polycyclic aromatic hydrocarbons (PAHs) will delay clearance from the respiratory tract. This clearance consists of a delayed penetration of the mucous lining layer (MLL), allowing mucociliary clearance, followed by a slow penetration of PAHs through walls of the conducting airways. To test this prediction, mucociliary clearance and retention in the mucosa of PAHs deposited in the conducting airways of the Beagle dog were measured. Mucociliary clearance of particles and dissolved PAHs was measured by instilling onto the MLL in a main stem bronchus or the distal trachea small volume of saline containing either dissolved benzo(a)pyrene (BaP) or phenanthrene (Phe), or a suspension of particulate solvent green (SG) or macroaggregated albumin (MAA). Sequential lavage of the mucous-retained materials followed the instillations. Retention of BaP in the airway walls of the bronchial tree was studied by instilling the hydrocarbon in an ethanol/saline solution at precise locations of the upper bronchial tree, and measuring the concentration of BaP and its major metabolites in the tissues. Results indicated that mucociliary clearance of SG and MAA particles in the trachea of the Beagle dog occurred at average rates of 27-30 mm/min. Of the two solutes, only the highly lipophilic BaP was sufficiently retained within the MLL to be transported with the mucociliary escalator. In addition, a fraction of the lipophilic materials cleared at a very rapid rate, in excess of 90 mm/min. This may indicate that one monolayer of pulmonary surfactant at the air interface is spreading out of the lungs on top of the MLL ata faster rate than mucociliary clearance. However, despite the protective properties of the MLL, fractions of BaP penetrating to the bronchial epithelium had a clearance half-time in the range of 1.4 hr, a period during which considerable metabolism of the PAH occurred. This long retention indicates a diffusion-limited uptake of BaP by the airways, and underscores the potential for local toxicity of highly lipophilic toxicants in the bronchial epithelium. PMID- 8346550 TI - Disposition of polycyclic aromatic hydrocarbons in the respiratory tract of the beagle dog. III. Mechanisms of the dosimetry. AB - The disposition of polycyclic aromatic hydrocarbons (PAHs) in the respiratory tract of the Beagle dog was measured and presented in two previous papers. In this paper, the data were used to demonstrate that highly lipophilic toxicants, such as PAHs, were diffusion-limited during clearance from the respiratory tract. Organic toxicants are usually regarded as perfusion-limited during clearance from the lungs. Within minutes after inhalation, the perfusion-limited substance is though to be cleared from all regions of the respiratory tract to the circulating blood. However, the length of time required for appearance of highly lipophilic PAHs in blood exiting the lungs following transient exposures of the alveolar region suggested that alveolar clearance of highly lipophilic PAHs was diffusion limited. But even though this transport was diffusion-limited, clearance of the highly lipophilic PAH benzo(a)pyrene (BaP) from the thin alveolar epithelium of the dog took only minutes, whereas clearance through the thicker epithelium of the conducting airways took hours. This phenomenon of slow airway clearance results from slower diffusion of highly lipophilic substances through the thicker air/blood barrier of the conducting airways compared to the thinner alveolar epithelium. A direct result of slowed clearance is a high concentration of BaP in the bronchial walls and an increased opportunity for metabolism to reactive forms. For this reason, the bronchial epithelium may become a preferential target of inhaled highly lipophilic toxicants. While the elevated dose during diffusion limited clearance involves only a few cell layers, the importance of this microdosimetry in contributing to local toxicity should not be overlooked. The findings suggest that bronchial cancer following inhalation exposures is more likely to be induced by highly lipophilic carcinogens such as PAHs than by less lipophilic carcinogens. PMID- 8346551 TI - Cyclins and cyclin-dependent kinases: take your partners. PMID- 8346552 TI - Reaction-induced infrared difference spectroscopy for the study of protein function and reaction mechanisms. AB - Infrared spectroscopic methods have been developed in the past decade to a sensitivity and selectivity which renders them useful for the study of enzyme function and enzyme reaction mechanisms. Originally developed as difference techniques for the investigation of light-induced reactions of photoreactive proteins, and matured in the field of bacteriorhodopsin and rhodopsin, they can now be used for the study of redox proteins by the use of electrochemical cells, or for the study of many different enzymes by the use of photolabile effector molecules. This brief review summarizes the currently available methods of infrared difference spectroscopy, the technical prerequisites, achievements and limitations. PMID- 8346553 TI - Multimeric complexes formed by DNA-binding proteins of low sequence specificity. AB - Some proteins bind to double-stranded DNA with low sequence specificity, forming regular multimeric complexes that extend over large regions of DNA, strongly distorting its conformation. Formation of these complexes at particular DNA sites usually depends on the structural ability of the DNA to follow the path imposed by the protein array. These complexes are found in both prokaryotic and eukaryotic organisms and participate in processes such as DNA replication, transcription and packaging. PMID- 8346554 TI - Lipocalins: do we taste with our tears? PMID- 8346555 TI - Ca(2+)-independent protein kinase Cs contain an amino-terminal domain similar to the C2 consensus sequence. PMID- 8346556 TI - The plant Golgi apparatus: a factory for complex polysaccharides and glycoproteins. AB - The Golgi apparatus of plant cells serves two major functions: it assembles and processes the oligosaccharide side chains of glycoproteins, and it synthesizes the complex polysaccharides of the cell wall matrix, the hemicelluloses and pectins. The first function is common to plant and animal cells while the second is unique to plants. The recent introduction of novel biochemical and electron microscopical techniques, as well as the production and the application of highly specific anti-glycan antibody probes have led to major advances in understanding the structural and functional organization of plant Golgi stacks. PMID- 8346557 TI - Lectin-carbohydrate complexes of plants and animals: an atomic view. AB - Lectins are a structurally diverse class of proteins, their only common features being the ability to bind carbohydrates specifically and reversibly, and to agglutinate cells. Some, however, can be grouped together into distinct families, such as those of the legumes or the cereals that are structurally similar, or the C-type (Ca(2+)-dependent) animal lectins that contain homologous carbohydrate recognition domains. Recent high-resolution X-ray crystallographic studies have revealed the structures of the sugar complexes of over half a dozen lectins. These studies demonstrate that the combining sites of lectins are also structurally diverse, although they may be similar in the same family. PMID- 8346558 TI - Screening for breast cancer: report of a population-based experience in the city of Milan, Italy. AB - AIMS AND BACKGROUND: Mammographic screening is recommended as a current health practice. The aim of the present study is to report the results of a new program which started in the city of Milan in 1989. METHODS: A total of 4882 women aged 50 to 61 years and resident in quarter no. 16 of Milan were invited by mail to attend the screening at the San Paolo Hospital based on two-view mammography and physical examination. RESULTS: A total of 2953 (60.5%) women attended the first screening round, and 18 cancers were detected (1 Tis, 8 T1, 9 T2). The detection rate was 6.9 x 1000, and the prevalence/incidence ratio was around 3.5. CONCLUSIONS: The study confirms the feasibility of breast cancer screening in an urban setting by using the existing general hospital facilities and should be considered as a possible model for other urban experiences. PMID- 8346560 TI - Is early gastric cancer, diffuse type, a forerunner of advanced gastric cancer. AB - AIMS AND BACKGROUND: Gastric cancer (GC) represents one of the most important causes of death by malignancy world wide. Our retrospective study was carried out on surgical stomach specimens obtained from a series of 552 consecutive cases of GC observed in the Departments of Surgical Pathology of the Public Hospitals of L'Aquila and Atri which cover the 17% of the entire population of the Italian Region Abruzzo. The aim of the study was to compare the anatomo-clinical characteristics of early GC (EGC) and advanced GC (AGC). METHODS: The diagnosis was achieved by the criteria of the Lauren's histopathological classification (intestinal and diffuse types). Our study also stratified the cases by sex, age, lymph node metastases and associated lesions such as chronic atrophic gastritis, intestinal metaplasia and dysplasia. RESULTS: On an average, patients affected by EGC were 8.1 years younger than those with AGC. This age gap could support the hypothesis that early lesions represent the first stage of AGC. However, when patients were subdivided according to Lauren's classification, the mean age of patients with EGC, diffuse type, was 12.2 years less than that of AGC patients of the corresponding histological type. Furthermore, the subset of patients with EGC, diffuse type, and lymph node metastases was 17.8 years younger than patients affected by AGC diffuse type, with lymph node metastases. CONCLUSIONS: The present study offers an original survey on GC in a defined Italian population. As far as the intestinal histotype is concerned, the slight age difference between EGC and AGC suggests that these tumors are different steps of the same process. On the contrary, the age distribution suggests that EGC, diffuse type, has a different biological behaviour. PMID- 8346559 TI - Secondary leukemia following treatment for Hodgkin's disease. AB - AIMS AND BACKGROUND: Patients treated for Hodgkin's disease with chemotherapy or with the association of chemotherapy and radiotherapy have an increased risk of secondary leukemia. The aim of this study was to evaluate the leukemogenic risk due to these treatment modalities. METHODS: We performed a case-control study on a population of 1410 patients treated for Hodgkin's disease from 1970 to 1990 in our Institute. Among these patients, we identified 25 cases of secondary leukemia and 3 cases of myelodysplasia, all occurring more than one year after the diagnosis of Hodgkin's disease. Three cases occurred among the patients treated with radiotherapy alone. When we analyzed the risk in relation to the type of treatment (radiotherapy, chemotherapy, or both), the comparisons were relative to patients treated with radiotherapy alone. RESULTS: We found that chemotherapy alone is associated with a fivefold increased risk (odds ratio = 5.4) compared with radiotherapy alone. When both treatments are used, the risk is not further increased (odds ratio = 4.4). Patients receiving more than 6 courses of chemotherapy have an excess risk (relative risk = 2.5) compared with those treated with 6 courses or less. No increased risk was observed after splenectomy. CONCLUSIONS: This study confirms an increased incidence of secondary leukemia occurring in patients treated for Hodgkin's disease. The increased risk seems to be correlated with the number of courses of alkylating agent therapy, whereas it is unaffected by the addition of radiotherapy. PMID- 8346561 TI - Infections in patients with acute non-lymphocytic leukemia nursed with central or peripheral venous access. AB - AIMS AND BACKGROUND: Infections are a major problem in patients undergoing induction chemotherapy for acute leukemia. Granulocytopenia is the single most important risk factor, but the pattern of infecting organisms can change according to nursing facilities or bacterial and fungal prophylaxis. METHODS: We reviewed the patterns and types of infections in 30 patients with acute non lymphocytic leukemia. Eighty-nine periods of neutropenia following chemotherapy were evaluated: in 60 courses patients had central and in 29 had peripheral venous access. RESULTS: Almost all patients (97%) became febrile after the 1st course of therapy, but one-third remained apyretic after the fourth course (P = 0.002). In this series, the incidence of gram-positive, gram-negative and mycotic isolations were respectively 76%, 18% and 6%. The need for antimicrobic treatment varied in relation to the course of chemotherapy. CONCLUSIONS: We conclude that in acute non-lymphocytic leukemia the first neutropenic period following the onset of disease is the most critical regarding infectious problems. Both quinolonic prophylaxis and central venous access could be responsible for the microbiologic findings. PMID- 8346562 TI - Fluorouracil plus folinic acid in metastatic adenocarcinoma of unknown primary site suggestive of a gastrointestinal primary. AB - AIMS AND BACKGROUND: The results of treatment strategies for carcinoma of an unknown primary location have been discouraging. Currently, no chemotherapeutic approach can be considered standard. METHODS: We therefore initiated a Phase II study in which fluorouracil (370 mg/m2, day 1 through 5) plus folinic acid (200 mg/m2 day 1 through 5) was administered in a subset of 17 patients (median age, 57 years) affected by histologically diagnosed adenocarcinoma of unknown primary location characterized by liver metastases and elevated CEA of CA 19.9. All of the patients had a performance status of 0-2 (ECOG Scale), and liver involvement was > 30% in 7 cases. RESULTS: No objective response was observed (4 cases of stabilization and 13 of disease progression). Median survival was 5 months. Toxicity was mild or moderate, and severe diarrhea was observed in only one case. CONCLUSIONS: The proposed regimen is inactive among this subset of patients and confirms that subdiaphragmatic metastases are related to a poor prognosis. Our results, in agreement with data published in the literature, suggest that patients affected by adenocarcinoma of an unknown primary origin metastatic to the liver and with a good performance status should be treated in an investigative setting. PMID- 8346563 TI - Antiemetic activity of oral lorazepam in addition to methylprednisolone and metoclopramide in the prophylactic treatment of vomiting induced by cisplatin. A double-blind, placebo-controlled study with crossover design. AB - AIMS AND BACKGROUND: It has been suggested that lorazepam has a definite role as an antiemetic drug in antiemetic cocktails. In this study we examined the antiemetic efficacy of metoclopramide (200 mg) and methylprednisolone (1000 mg) with or without lorazepam. METHODS: Sixty patients treated with cisplatin containing regimens were entered into a randomized, double-blind study with cross over. Lorazepam 2.5 mg or placebo were administered orally the evening before therapy and just after the beginning of fluid infusion for chemotherapy. Degree of nausea and number of vomiting episodes, together with somnolence, were recorded on a data flow sheet and visual-analogue scales. RESULTS: 100 cycles (50 patients) are evaluable. In 39 cycles there was no nausea and vomiting, in 74 cycles acceptable control of emesis was reached (0-2 episodes of vomiting), without significant differences among the two arms. However, nausea was shorter in lorazepam arm (p < 0.01), and 80% of the patients preferred treatment with lorazepam (p < 0.003). Anxiety was reduced in the patients treated with lorazepam (p < 0.4). CONCLUSIONS: Lorazepam improves tolerability to cisplatin-containing chemotherapy, mainly by influencing the psychological status of the patient and favoring the amnestic process. PMID- 8346564 TI - Nasopharyngeal carcinoma in children and adolescents successful role of retrieval therapy. AB - BACKGROUND: The nasopharyngeal carcinoma in children and adolescents usually presents in advanced locoregional stages. METHODS: Seventeen patients, below the age of 18 years, with the diagnosis of nasopharyngeal carcinoma were diagnosed and treated at the National Cancer Institute (NCI), Cairo, Egypt, during the period 1982-1987. These 17 patients were selected from 28 patients of the same age group to whom the diagnosis of nasopharyngeal malignancies were established. This diagnosis was confirmed morphologically and with immunostaining using antibodies against leucocyte common antigen (LCA), epithelial membrane antigen (EMA), cytokeratin and vimentin. RESULTS: Eighty two percent of our patients were in T3 + T4 and 94% had N 1-3 nodal status. The locoregional control was 94% with adequate conventional radiotherapy, while the distant metastasis rate was also high (81%). The 5-year actuarial survival rate was 47 +/- 11% and the survival worsened with the advancement in T stage. However, the present study did not show any influence of N stage on survival. The relatively high survival rate depended mainly upon successful retrieval therapy with radiochemotherapy. CONCLUSIONS: This emphasizes the role of combination chemotherapy in the treatment of relapsing nasopharyngeal carcinoma in young patients. PMID- 8346565 TI - The basement membranes in sarcomatoid carcinomas. An immunohistochemical study. AB - AIMS: Eight sarcomatoid carcinomas from various anatomical locations were investigated by immunohistochemical staining to laminin, type IV collagen and heparan sulfate proteoglycan, to study the characteristics of basement membranes at the interface between carcinomatous and sarcomatous tissues. METHODS: Paraffin wax embedded tissue sections from representative tumor samples have been stained with specific antibodies, using the peroxidase-antiperoxidase technique. RESULTS: In all cases several interruptions or discontinuities of the basement membrane staining pattern were seen. In 4 cases, larger defects or complete loss of staining was also noted. At these places, the boundaries between carcinomatous and sarcomatous tissue were often blurred. CONCLUSIONS: Disruption and loss of basement membranes at interface between carcinomatous and sarcomatous tissues is a frequent finding in sarcomatoid carcinomas. These changes could be consistent with an epithelial origin of the sarcomatous component in these tumors by means of an epithelial-mesenchymal conversion mechanism. PMID- 8346567 TI - Kasabach-Merritt syndrome associated to angiosarcoma of the breast. A case report and review of the literature. AB - INTRODUCTION: Kasabach-Merritt syndrome is characterized by the association of a consumptive thrombohemorrhagic disorder and angioma occurring usually in children. In the present study, a case of Kasabach-Merritt syndrome associated to an angiosarcoma of the breast is reported. CLINICAL HISTORY: The tumor together with the thrombohemorrhagic disorder manifested in a 28-year-old woman. The patient underwent mastectomy. The tumor recurred in the same site 2 years later. The patient died of severe anemia 8 years after the first appearance of the angiosarcoma. MATERIAL AND METHODS: Tissues were formalin fixed and paraffin embedded; in addition, selected sections were immunohistochemically stained. RESULTS AND CONCLUSIONS: A well-differentiated angiosarcoma was visible throughout the removed organ. A review of the literature showed that only 6 cases of Kasabach-Merritt syndrome associated to malignant vascular tumors have been previously reported. All these 6 cases occurred in adult patients. On the contrary, Kasabach-Merritt syndrome associated to benign vascular tumors affects children. This is the first case occurring in the breast. PMID- 8346566 TI - Study of the HLA-DP beta 1 locus by the polymerase chain reaction technique in patients with Hodgkin's disease. AB - BACKGROUND: A number of reports have studied associations between Hodgkin's disease and HLA. Some of them established correlation between several antigens and Hodgkin's disease, and others found no correlations. METHODS: The HLA DP locus was determined by the polymerase chain reaction method in 31 Hodgkin's disease patients and 58 healthy controls. RESULTS: No significant difference between patients and controls was noted. CONCLUSIONS: Further investigations are needed to confirm the hypothesis of a possible role of the HLA complex as one of the factors involved in Hodgkin's disease. PMID- 8346568 TI - Cavitation of lung metastases from bladder cancer. Report of two cases. AB - We describe 2 cases of cavitary lung metastasis from bladder cancer and retrospectively analyze the frequency of such an event in our environment. Although rare, this finding is not exceptional and should be taken into account when clinicians and oncologists face the differential diagnosis of pulmonary cavitation. Moreover, a cavitary pulmonary nodule may also be the presenting sign of bladder cancer. PMID- 8346569 TI - Epididymal lymphoma. A case report. AB - Primary epididymal lymphoma is an unusual observation. Only 2 cases of non Hodgkin's lymphoma of the epididymis have been previously reported. We describe the clinical and pathologic features and management of a primary high-grade malignant lymphoma of the epididymis in which a tentative diagnosis of lymphoma was made on the basis of cytologic examination and immunochemical staining of the material obtained from an aspiration needle biopsy. PMID- 8346571 TI - [Treatment of rheumatoid arthritis--are we good enough?]. PMID- 8346570 TI - Sarcomas involving the abdominal and pelvic cavity. AB - The principles of management of all sarcomas that involve the abdominal and pelvic cavity are presented. The anatomic sites for the primary malignancy include retroperitoneal sarcomas, pelvic side-wall sarcomas, sarcomas arising from the abdominal viscera, and sarcomas arising from the pelvic organs. All histologic types of sarcomas may be considered together when therapeutic options are being discussed. This presentation stresses surgical removal with an adequate margin of resection as the principal goal of management. The curative treatment of these cancers places great emphasis on the surgeon's knowledge of anatomy, technical skills, innovation, and surgical courage. Systemic chemotherapy and radiotherapy have not shown reproducible efficacy. Complete resection in the absence of tumor spillage remains the only reliable treatment option. Possible benefits of induction chemotherapy and intraperitoneal chemotherapy using cisplatin and doxorubicin in the early postoperative period are presented. PMID- 8346572 TI - [Methotrexate therapy of rheumatoid arthritis. An open observation study of 110 patients with median length of treatment of 17.8 month]. AB - Effects and side-effects of treating patients with rheumatoid arthritis with methotrexate given as weekly pulse-treatment are examined in an open observation study. One hundred and ten consecutive patients with active rheumatoid arthritis entered the study. Six criteria of remission were registered as effect variables. Median length of treatment at the time of investigation was 17.8 months. At this point, 34 patients were in complete remission, with a median effect score of five point five out of six possible points. Twenty-nine were in partial remission and 47 (42.7%) had not improved. The median effect score for all patients was three point 6 (95% confidence limits (2-4). Methotrexate treatment was stopped in 24 patients, in 15 of these because of a combination of side-effects and lack of therapeutic response. Prednisone treatment could be discontinued in 20 out of 57 patients during the course of methotrexate treatment. Side-effects were registered in 67 cases (62.7%), and led to treatment being discontinued in 21 cases. Nearly half the side-effects consisted of dyspepsia and rises in amino transferase levels (48 of 67 patients). Consistently raised amino-transferase levels were found in five cases, all returned to normal after methotrexate was stopped. Serious side-effect were registered in four cases, consisting of two cases of short-term pancytopenia following overdosage and two cases of severe hypoxia following methotrexate-induced alveolitis. PMID- 8346573 TI - [Experimental gastrointestinal motility]. AB - Gastrointestinal motility is a major field of research today; however, despite there being a huge amount of available data in the literature, its exact role as a diagnostic tool has yet to be defined. The purpose of this paper is to describe some of the existing experimental models and methods for conducting motility studies. PMID- 8346574 TI - [The Thule case. Mortality and hospitalization after the crash of an American B 52 bomber in 1968]. AB - In 1968, a B-52 bomber carrying nuclear bombs crashed near the Thule US Air-Base in Greenland. By 1986, many cases of disease had been reported among Danish workers employed at the base. A database has been constructed from staff files of workers employed from 1963 to 1971. Of 4,322 workers, 98.7% were identified in 1987. The study group consisted of 1,202 workers employed during the clean up period (from the time of the crash until the last of the contaminated material had been removed). The reference group consisted of 3,120 workers employed outside the clean up period. No differences were found in total mortality, or mortality from cancer, heart disease or accidents between the groups after adjusting for age, marital status and length of employment. Mortality from suicide was lower in the study group. The hospitalization rates for the period 1977-1985 also showed no differences between the two groups. The conclusion of the register surveys is that no harmful effect on health due to the crash can be established by measuring mortality or hospital admissions. PMID- 8346575 TI - [Tobacco, lung cancer and chronic obstructive lung disease. Results from the Osterbro study]. AB - Data from The Copenhagen City Heart Study, a prospective population study, were analysed to investigate the influence of the type of tobacco and inhalation on mortality from lung cancer and chronic obstructive pulmonary disease (COPD). The study sample comprised 2986 plain cigarette smokers, 3222 filter cigarette smokers, 1578 smokers of cheroots/cigars, 433 male pipe smokers and 773 smokers smoking more than one type of tobacco. From 1976 to the end of 1989 we observed 268 deaths from lung cancer and 195 deaths, where COPD was considered as either the main or the contributory cause of death. Current smokers of all types of tobacco had a significantly higher risk of mortality from the investigated diseases than never-smokers. In both sexes the risks of death from both lung cancer and COPD were lower in cheroot/cigar smokers and in pipe smokers than in cigarette smokers, but these differences were markedly diminished after an adjustment for the inhalation habit. The present study substantiates that tobacco smoking increases pulmonary mortality. The small differences between the various types of tobacco are probably caused by different inhalation patterns. PMID- 8346576 TI - [How much is lung function affected by smoking and occupation? Dichotomy of continuous variables can change the results]. AB - Data from a cross-sectional study of 1045 men comprising a random population sample (768 men) and a sample of cement workers (277 men) were analyzed in order to examine the effects of smoking and occupation on forced expiratory volume in one second (FEV1). The continuous FEV1 variable and five dichotomous FEV1 variables based on % of predicted were analyzed. Differences between the "relative importance" of smoking and occupation were found to depend on the choice of the FEV1 variable. The effects of occupation compared with the effects of smoking varied considerably with different FEV1 variables, continuous or dichotomized at different cut-off levels. We conclude that comparison of surveys utilizing different FEV1 variables must be made with caution. PMID- 8346577 TI - [Displaced proximal humeral fracture--conservative treatment]. AB - The results of 42 patients with displaced proximal humeral fractures treated by conservative methods were reviewed. Follow-up evaluation included clinical and radiographic examination median two years after the trauma. The results were assessed using Neer's protocol. The patients were asked to assess the results. The patients assessed the results better than the Neer score (p < 0.001). The patients' response to non-operative treatment was satisfactory. It is concluded that the Neer classification of the results underestimates the degree of satisfaction achieved by the patients. It is concluded that displaced proximal humeral fractures can be treated satisfactorily by non-operative methods. PMID- 8346578 TI - [Corticosteroid treatment of patients with AIDS and severe Pneumocystis carinii pneumonia. A European multicenter study. Danish-Dutch AIDS Study Group]. AB - Fifty-nine HIV-1 infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on: 1) survival to discharge, 2) need for mechanical ventilation (MV) and 3) survival at day 90. CS was given within 24 hours of standard therapy as intravenous methylprednisolone 2 mg/kg bodyweight daily for ten days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 < 9.0 kPa (67.5 mmHg) and/or a PaCO2 < 4.0 kPa (30.0 mmHg). During the acute episode of PCP nine (31%) of the 29 control patients died versus three (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and three (10%) in the KS group; p = 0.01. The 90-day survival was 69% in patients receiving cotrimoxazole alone versus 87% in patients receiving adjunctive KS; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS-patients reduces the acute mortality and the need for mechanical ventilation. PMID- 8346579 TI - [Use of bladder thermistor catheters in an intensive care unit. Comparative study of core temperature measurements with bladder thermometers and rectal thermometers in an intensive care unit]. AB - Bladder temperature measured by a thermistor tipped urinary catheter was compared to rectal temperature in 14 ICU patients. During a period of five days 2 x 232 measurements were recorded, and good correlation was found between rectal and bladder temperatures (R = 0.97). There did not seem to be any drift in the bladder thermistor. Measurement was accurate during periods of oliguria. We find that bladder temperature measurement is reliable, safe, convenient and accurate for routine use in the ICU. PMID- 8346580 TI - [Infections after insertion of epidural catheters]. AB - Three cases of iatrogenic infection following the insertion and subsequent use of an epidural catheter are described. The development, symptoms, diagnostic possibilities and treatment of epidural abscess are described. It is stressed that patients with decreased immunological defences are more prone to infection. Two patients with epidural abscesses are described. In both cases there was a "doctors-delay" before diagnosis was reached. Despite neurosurgical intervention both patients developed paralysis of the lower extremities, bladder and intestinal function, in one of them irreversibly. We also describe one patient who developed meningitis following eight attempts to insert an epidural catheter. The importance of quick diagnosis and intervention is stressed as well as the importance of strict sterility while inserting and using epidural catheters. PMID- 8346581 TI - [Spontaneous bladder perforation--a rare complication of neurogenic bladder dysfunction]. AB - Spontaneous rupture of the urinary bladder which is not associated with trauma is uncommon. A case of spontaneous bladder perforation (triggered by an episode of urinary retention) and peritonitis in a 69-year old male patient with neurogenic bladder dysfunction is reported. The latter was due to disseminated sclerosis and was complicated by recurrent urinary tract infection and two bladder calculi. The etiology, diagnosis and treatment of spontaneous bladder perforation is briefly discussed. The diagnosis spontaneous bladder perforation should be considered in patients with non-characteristic acute abdominal conditions and voiding symptoms, especially if they have neurogenic bladder dysfunction and a history of recurrent lower urinary tract infections and/or bladder calculi. We recommend that bladder stones should be removed--also in asymptomatic cases. PMID- 8346582 TI - [2 cases of lymphangioleiomyomatosis treated by hormonal manipulation]. AB - The course of disease in two women with bioptically verified lymphangioleiomyomatosis (LAM) is demonstrated. One was oestrogen- and progesterone-receptor negative, but responded promptly to hysterosalpingo oophorectomy and has had no symptoms later. The other was receptor positive, but in spite of hysterosalpingo-oophorectomy and hormonal manipulation with tamoxifen and medroxyprogesterone, has had a complicated course of the disease with symptoms for ten years. LAM is a hormone dependent disease, but our knowledge is still incomplete. Hormonal manipulation should be tried in receptor positive as well as negative patients. Tamoxifen seems to have deleterious effects on the course of disease. PMID- 8346583 TI - [Children in families with alcohol and drug problems]. PMID- 8346584 TI - [Complications of MMR vaccinations]. PMID- 8346585 TI - [Toxic epidermal necrolysis]. PMID- 8346586 TI - [Travelers' diarrhea]. PMID- 8346587 TI - [Ingestion of caustic agents. Epidemiology, pathogenesis, course, complications and prognosis]. AB - The incidence of caustic ingestion varies with the availability of caustic products and preventive measures. A transient increase was seen in the US round 1970, in Denmark in the late seventies. Diagnosis and treatment of caustic ingestion injuries remains controversial, and must to a high degree be based on retrospective studies and animal studies, especially concerning the pathology and clinical course of the disease. These subjects are reviewed together with complications and prognosis. It is stressed, that ingestion of alkalies and acids result in a variety of lesions, depending on a number of factors listed. Ingestion of alkalies occurs in approximately 85% of all cases, with oesophageal stricture as the most frequent complication, and tracheal necrosis as the most frequent cause of death. Ingestion of acid in large amounts may lead to early gastric perforation, massive metabolic acidosis, and eventual death. Pyloric stenosis is the most common complication of acid ingestion. Approximately 33% of all patients admitted with (suspected) caustic injury reveal oesophageal damage. This leads to subsequent oesophageal stricture in 10-15%. Mortality is less than 10% in unselected groups. PMID- 8346588 TI - [Salmon calcitonin in osteoporosis. The effect of intranasal application on bone mineral content and fracture frequency in postmenopausal women with manifest osteoporotic changes]. AB - The objective was to study the dose-related response of intranasal salmon calcitonin (Salcatonin) on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. A total of 208 healthy women aged 68-72 years, who had a bone mineral content (BMC) of the distal forearm 30% below the mean value for healthy premenopausal women, were examined in a double-blind, placebo-controlled, randomized group comparison study. They were randomized to a two-year daily treatment of either 50 IU, 100 IU, 200 IU Salcatonin or placebo. All received 500 mg calcium daily. In the calcium-(placebo)-treated group the BMC of the spine increased 1%, whereas an increase of 3% was seen in the 200 IU Salcatonin treated group. There was a dose related response to Salcatonin manifested by an increase in BMC of 1.0%/100 IU. The incidence of new fractures was significantly lower in the women treated with Salcatonin (about one third of that in the non-Salcatonin treated women). In conclusion the results suggest that, compared with calcium alone, Salcatonin given intranasally reduces the rate of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner. PMID- 8346589 TI - [No increase in the prevalence of vertebral fractures among postmenopausal women over a 10-year period]. AB - We examined whether the prevalence of vertebral fracture in otherwise healthy, 70 year-old Danish women had increased over a period of ten years. The population based, epidemiological study included two age-matched, representative samples of postmenopausal women. Group 1 (1979) consisted of 173 healthy women without secondary causes of osteoporosis, Group 2 (1989) of 387 women. X-rays of the thoraco-lumbar spine were assessed for vertebral fracture by five radiological methods. There was no significant difference between the two groups in the prevalence of vertebral fracture and the 95% confidence intervals overlapped completely in all methods. The prevalence rates varied by method from 35% to 80% but the distribution of fracture types was similar in the two groups. We conclude that the prevalence of vertebral fractures due to postmenopausal osteoporosis has not increased since 1979 in suburban Copenhagen, and that comparison of prevalences requires the same method of radiological assessment. PMID- 8346590 TI - [Significant prognostic factors for recurrence-free survival after surgical treatment of head-neck melanoma]. AB - The clinico-pathological and therapeutic data of 512 patients with clinical stage I invasive head and neck melanoma of the skin were re-evaluated. There were 287 females and 225 males. The median age at primary surgery was 65 years, range 18 to 96 years. The median observation period was 5 years, range 1 month to 25 years. Sex, age, ulcerated tumor and tumor thickness were found by Cox multivariate regression analysis to act as independent prognostic factors for recurrence-free survival. In addition, size of the excision margin was found of no significance for survival without relapse when adjusting for the independent risk factors. PMID- 8346591 TI - [Early complications of enterostomy. Importance of the type of suture]. AB - The frequency and character of early complications following creation of enterostomies, and their relation to the type of suture material used were studied in 50 consecutive patients. The stomas were matured by muco-cutaneous eversion, and were fixated with Maxon 4-0 and Vicryl 3-0 sutures. Half the stoma circumference was sutured with the one suture type, and the other half with the other. No statistically significant correlation was found between enterostomy type or surgical procedure and complications. The incidence of muco-cutaneous complications was significantly higher following fixation with Vicryl as compared to Maxon sutures. The cause of this difference is uncertain, however, the physical configuration of the sutures seems important, Maxin being monofile versus Vicryl being braided. Whether the chemical structure is significant as well remains undetermined at present. PMID- 8346593 TI - [Angiotensin I converting enzyme inhibitor enalapril in treatment of progressive chronic nephropathy. An open randomized controlled trial]. AB - In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomised in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least two years or until they needed dialysis. The therapeutic goal, was a blood pressure of 120 ti 140/80 to 90 mmHg. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to 7.11) mL/min/1.73 m2/month, and in the control group, it was -0.31 (+0.01 to 1.97) mL/min/1.73 m2/month (p < 0.05). There was no significant difference in blood pressure between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy. PMID- 8346592 TI - [Radioiodine therapy of recurrent hyperthyroidism in patients previously treated for diffuse toxic goiter with subtotal surgery]. AB - Radioiodine therapy is often employed for treatment of patients with relapse of hyperthyroidism due to Graves' disease, after previous thyroid surgery. Little is known about the outcome of this treatment compared to patients with no previous surgery. A total of 20 patients, who had received surgical treatment for Graves' hyperthyroidism 1-46 years previously and with relapse of hyperthyroidism, and 25 patients with hyperthyroidism due to Graves' disease and no previous thyroid surgery were treated with radioiodine, following the same protocol. Early after treatment the previously operated patients showed a higher sensitivity to radioiodine, with more cases of early hypothyroidism than non-operated patients. However, after 50 months of follow-up the outcome was identical. The results indicate that frequent assessment is necessary after radioiodine treatment of patients with previous thyroid surgery, since some patients develop early hypothyroidism. PMID- 8346595 TI - [Facial erysipelas]. AB - Facial erysipelas is quite uncommon today in Denmark. However, as the disease may be fatal without the proper treatment, the necessity for definite diagnosis is stressed on the basis of a case. PMID- 8346594 TI - [Diaphragm-like strictures of the small intestine after treatment with non steroidal anti-inflammatory agents]. AB - Although final proof of a causal relationship is missing, it is believed that NSAID-induced lesions in the distal gut are common. We present a case where nine years of NSAID treatment appears to have caused characteristic, membrane-like strictures of the small intestine, and give a brief discussion of the possible pathogenetic mechanisms. PMID- 8346596 TI - [Back pain in abdominal aortic aneurysm]. AB - Back pain is a typical symptom of abdominal aortic aneurysm. Symptoms of root compression may also be present if the aneurysm has caused changes to the vertebral column. A typical case is presented. The condition is life-threatening and requires vascular reconstruction. PMID- 8346598 TI - [Antidepressive therapy]. PMID- 8346597 TI - [Purulent arthritis after blockade treatment]. AB - Injections of local anaesthetics with or without steroids are widespread in the treatment of muscular pain. Occasionally, however, they are followed by serious bacterial infections. Three cases of septic arthritis, one localised to the hip, one to the knee and one to the sacroiliac joint are presented. One should offer great consideration to the possible complications following injections into or near joints. PMID- 8346599 TI - [Perinatal autopsy of stillborn infants]. PMID- 8346600 TI - Doppler color flow images of iliofemoral graft end-to-side distal anastomotic models. AB - Hemodynamics within the distal anastomoses of iliofemoral bypass grafts were simulated using Plexiglas models (2.5 cm ID) within a pulsatile flow loop system (Re(mean) = 92, Re(peak) = 459 and alpha = 3.56). End-to-side distal anastomoses were constructed with angles of 30 degrees, 45 degrees and 60 degrees to bypass proximal artery segments with stenoses of 60% and 100% diameter reduction. Velocities were obtained over a two-dimensional field within the artery using an ultrasonic Doppler color flow imager operating at 5 MHz at positions from 1.5 diameters upstream to 3 diameters downstream of the anastomosis. Flow patterns downstream of an occlusion demonstrated definite skewing effects toward the outer wall with resultant flow separation along the inner wall. Presence of a partial (60% diameter reduction) arterial stenosis upstream of the anastomosis produced flow separation along both artery walls and a more symmetric profile downstream. Measurement of a separation area index (SAI) along each arterial wall demonstrated a minimum area exposed to low velocities for the 30 degrees anastomotic angle compared to the 45 degrees and 60 degrees anastomotic angles and for the occluded proximal artery cases compared to corresponding stenotic artery cases. The SAI values were minimal at peak systole compared to successive quarter cycle intervals. The findings of this study provide further information regarding the relationship between local fluid mechanics and predominant sites for intimal hyperplasia formation. PMID- 8346601 TI - Doppler quantification of echo-contrast injections in vivo. AB - It is difficult to quantify myocardial perfusion using contrast echocardiography because the echogenicity of injected contrast is unknown. We propose that a measurement of Doppler amplitude from blood in a systemic artery during the passage of contrast could define the needed input function. Time-amplitude curves from pulsed Doppler cuffs on coronary and carotid arteries of 7 dogs were analyzed during aortic root and left atrial injections of Albunex. We found in individual animals that the areas under the Doppler time-amplitude curves were correlated to the amount of Albunex injected (R = 0.87-0.99), inversely correlated to cardiac output (R = 0.83), and uncorrelated to coronary flow (R = 0.18). Due to better mixing, the coronary and carotid response areas correlated better for left atrial injections (R = 0.96) than for aortic root injections (R = 0.56). We conclude that Doppler amplitude detection can be used to quantify the passage of echo-contrast agents, that the measurements comply with indicator dilution principles, and that systemic measurements in the carotid artery could be used to predict the coronary input function for injection sites with good systemic mixing. PMID- 8346602 TI - Quantification of transpulmonary echocontrast effects. AB - Videodensity of left heart and right heart were studied after intravenous injection of increasing dosages of 0.01-0.02 and 0.04 mL/kg bodyweight of Albunex in 10 healthy volunteers. The increase in videodensity in the left ventricle was always lower than in the right ventricle. Possible explanations are diffusion of gases caused by ambient pressures changes and change in microspheres distribution due to the sieving effect of the lung capillary bed. These phenomena were studied in vitro and were consistent with clinical observations. These limitations restrict a quantitative assessment of left heart echocontrast after intravenous injection. PMID- 8346603 TI - Quantitative echo contrast concentration measurement by Doppler sonography. AB - The hypothesis investigated in this study is that Doppler ultrasound can be used to make quantitative echo contrast concentration measurements in flow systems. Our motivation was to demonstrate the utility and some of the pitfalls of using scattered ultrasound intensity to quantify echo contrast in chambers and vessels. Doppler ultrasound was used rather than conventional imaging techniques because of its natural association with the assessment of flow in chambers and vessels. We compared the intensity of audio Doppler to various steady-state concentrations echo contrast in a carefully controlled in vitro flow system. A total of 62 paired audio Doppler intensity and echo contrast concentration measurements were made. A weak positive correlation was found between the absolute echo contrast concentration and audio Doppler intensity (r = 0.510, p = 0.001). The correlation was weak because of the many unknowns and effervescent nature of microbubble echo contrast agents. However, audio Doppler intensity was shown to correlate strongly with the relative concentration of echo contrast over short time periods (r = 0.958, p = 0.0001). The results show that Doppler intensity can be used to quantitatively measure the relative, but not the absolute concentration of echo contrast in in vitro flow systems. PMID- 8346604 TI - Ultrasonic tissue characterization of experimental venous intimal hyperplasia. AB - Ultrasonic tissue characterization (UTC) employing slope and Y-intercept parameters from the normalized power spectrum of backscattered echoes was employed in vivo to study compositional changes in the walls of pig jugular veins in which thrombi were experimentally induced. Light microscopy revealed these changes to be intimal hyperplasia with an early predominance of smooth muscle cells and a later mixture of smooth muscle cells and collagen deposits. UTC distinguished intimal hyperplasia from previously reported data from luminal thrombosis UTC. Furthermore, UTC was able to discriminate between early (predominantly smooth muscle cells) and older (smooth muscle cells plus collagen deposits) intimal hyperplasia. The study suggests that intimal hyperplasia in the experimental model used may be organized thrombus and that UTC may be able to follow both the development of wall changes as well as luminal changes occurring in venous thrombosis. PMID- 8346605 TI - Experimentally induced changes in heart rate alter umbilicoplacental hemodynamics in fetal sheep. AB - In the anesthetized sheep fetus, we have accelerated heart rate by atrial pacing (n = 6) or caused decelerations by stimulating the vagus nerve (n = 7). Alterations in heart rate were linearly related to changes in the ratio of the diastolic minimum (D) to systolic maximum (S) of flow and velocity, and to changes in the flow pulsatility index in the umbilical artery. Decelerations slightly increased vascular resistance, and decreased blood flow and mean arterial pressure, but accelerations had no significant effect. The index of impedance was unaltered by either intervention. The major factor mediating the influence of heart rate on blood flow pulsatility in the umbilical artery was the aortic blood pressure pulsatility. An equation was derived to adjust flow D/S to a standardized heart rate. Results showed that heart rate correction can affect the interpretation of experimental data. PMID- 8346606 TI - Estimation of in situ ultrasound exposure during obstetric examinations. AB - Layered tissue models are developed to estimate in situ ultrasound intensity during common obstetric examinations by incorporation of measured overlying tissue thicknesses with data on the attenuation properties of tissues. Results are compared with attenuation models recommended by the United States Food and Drug Administration (FDA) and National Council on Radiation Protection and Measurements (NCRP). For abdominal and transvaginal scanning in the first trimester, fixed attenuation models based on attenuation values of 1.2 dB/MHz and 0.6 dB/MHz, respectively, are representative of worst-case exposure conditions. For second and third trimesters, a fixed attenuation value of 0.8 dB/MHz is representative of worst-case exposure conditions. A fixed attenuation value of 1.0 dB/MHz is suggested for common Doppler examinations. The study suggests that the FDA-derating factor of 0.3 dB/cm.MHz may not give a conservative estimate of in situ intensity for certain obstetric examinations. PMID- 8346607 TI - Transient acoustic cavitation in gallstone fragmentation: a study of gallstones fragmented in vivo. AB - The mechanism of gallstone fragmentation by shock waves in vivo is uncertain. We used scanning electron microscopy to study 9 partially fragmented stones obtained from 6 patients who underwent lithotripsy and subsequently had surgery because of incomplete fragmentation. Surface characteristics of the stone were studied using scanning electron microscopy and compared to gallstones fragmented in degassed water in vitro and to control stones obtained from patients with uncomplicated cholelithiasis. Characteristic damage caused by transient acoustic cavitation was visible in all stones fragmented in vivo and in vitro as pits 10-100 microns diameter. In these pits, cholesterol crystals were fractured, and the symmetry of crystal boundaries was damaged. In areas of more severe damage, individual pits coalesced to form craters on the stone surface. High magnification of the pit walls revealed cracks, which in some instances radiated out onto the unpitted surface of the stone. We conclude that transient acoustic cavitation plays a role in gallstone fragmentation in vivo through the mechanism of surface pitting and the formation of cracks that radiate outward from the surface pits. Measures to enhance cavitation may improve the results of gallstone lithotripsy. PMID- 8346608 TI - Ultrasonic gas body activation in Elodea leaves and the mechanical index. AB - Membrane damage resulting from ultrasonic gas body activation was investigated in leaves of the aquatic plant Elodea using pulse-mode exposures from 0.745-15 MHz. The frequency response was similar to that previously observed for continuous exposures. Cell death thresholds were higher for the pulse modes; for example, at 6 MHz the threshold was 166 W/cm2 spatial-peak, pulse-average (SPPA) intensity for 1 microsecond pulses and 1 kHz pulse repetition frequency (PRF) for 60 s exposures, compared to 12 W/cm2 for 60 ms continuous exposure. Increasing the PRF for 2.5 MHz, 3 microseconds pulses from 10 Hz to 5 kHz resulted in a gradual decrease in the threshold. Increasing the pulse duration from 1 microsecond to 30 microseconds and PRF from 33 Hz to 1 kHz only weakly influenced the threshold, for the constant 60 ms total on-time. Decreasing the pulse duration for single 6 MHz pulses increased the threshold up to 1,540 W/cm2 at 30 microseconds. The gas body activity was modeled with linear theory for oscillation of the gas channel walls, and intracellular shear stress, which causes lethal damage to the plasma membranes, was modeled with theory for acoustic microstreaming. Theory and observation indicate that the minimum shear stress threshold as a function of resonance frequency has essentially the same form as the Mechanical Index (MI) in the 0.5 to 20 MHz range. Specifically, for 3 microseconds pulses with 0.2-2 kHz PRF and 60 ms total on-time, the pressure-amplitude threshold divided by the square root of the frequency was approximately constant at 0.95 MPa/MHz1/2. PMID- 8346609 TI - An efficient computer model of three-dimensional speckle patterns in dynamically focused annular array. AB - This paper describes an efficient computer method for generating three dimensional (3-D) ultrasonic speckle patterns for sector scans of an annular array with dynamic focusing in both transmit and receive. Assuming random scatterers in an attenuating medium, the system synthesizes the waveform for each scan line using echo data received at all annular elements of the transducer when short pulses are transmitted by one annulus after another. The amount of echo data needed to synthesize one waveform is tremendously reduced by reducing the 3 D distributions of scatterers to line distributions and by representing scatterers on a small line segment by a single equivalent scatterer taking into account the two-way travel time differences. Furthermore, by a judicious 3-D arrangement of the scatterer lines and scan lines, it is possible to synthesize the waveform for a new scan line with negligible computation overhead. The waveforms of the scan lines are detected to obtain a B-mode image or speckle patterns. The patterns obtained on several differently-oriented image planes showed a good statistical agreement with experimentally obtained patterns. PMID- 8346610 TI - Deconvolution of in-vivo ultrasound B-mode images. AB - An algorithm for deconvolution of medical ultrasound images is presented. The procedure involves estimation of the basic one-dimensional ultrasound pulse, determining the ratio of the covariance of the noise to the covariance of the reflection signal, and finally deconvolution of the rf signal from the transducer. Using pulse and covariance estimators makes the approach self calibrating, as all parameters for the procedure are estimated from the patient under investigation. An example of use on a clinical, in-vivo image is given. A 2 x 2 cm region of the portal vein in a liver is deconvolved. An increase in axial resolution by a factor of 2.4 is obtained. The procedure can also be applied to whole images, when it is ensured that the rf signal is properly measured. A method for doing that is outlined. PMID- 8346611 TI - Producing deep depth of field and depth-independent resolution in NDE with limited diffraction beams. AB - Limited diffraction beams, such as Durnin's J0 Bessel beam, are a class of nonspreading solutions to the isotropic/homogeneous scalar wave equation. These beams can be approximately produced with finite aperture and energy over a deep depth of field. In this paper, we report the application of a broadband J0 Bessel beam to nondestructive evaluation (NDE) of materials. Pulse-echo images of a stainless steel block phantom were obtained with both the J0 Bessel beam and a conventional focused Gaussian beam. Results show that uniformly high resolutions were obtained with the J0 Bessel beam over a large distance. In addition, the lateral resolution of the J0 Bessel beam is almost independent of the speed of sound of the materials inspected. In contrast, the lateral resolution of images obtained with the conventional focused Gaussian beam changes dramatically with the distance and the focal length of the beam in water is greatly reduced by the steel block. Therefore, limited diffraction beams could be useful for nondestructive evaluation of materials of different speeds of sound. Restoration of pulse-echo images obtained with these beams could be simplified. PMID- 8346612 TI - Elastography: elasticity imaging using ultrasound with application to muscle and breast in vivo. AB - Changes in tissue elasticity are generally correlated with its pathological state. In many cases, despite the difference in elasticity, the small size of a lesion or its location deep in the body preclude its detection by palpation. In general, such a lesion may or may not possess echogenic properties that would make it ultrasonically detectable. Elastography is an ultrasonic method for imaging the elasticity of compliant tissues. The method estimates the local longitudinal strain of tissue elements by ultrasonically assessing the one dimensional local displacements. This information can be combined with first order theoretical estimates of the local stress to yield a quantitative measure of the local elastic properties of tissue. The elasticity information is displayed in the form of a gray scale image called an elastogram. An experimental system for elastography in phantoms based on a single element transducer has been described previously [1]. Here we introduce a new elastography system based on a linear array transducer that is suitable for in vivo scanning. We describe tissue mimicking phantom experiments and preliminary in vivo breast and muscle elastograms confirming the feasibility of performing elastography in vivo. An elastogram of a breast containing an 8 mm palpable cancer nodule clearly shows the lesion. Elastograms and their corresponding sonograms show some similarities and differences in the depiction of tissue structures. PMID- 8346613 TI - Reduction of image noise in elastography. AB - Elastography is a method for imaging the elastic properties of compliant tissues which produces gray scale elasticity images called elastograms. The elastograms of phantoms with homogeneous elastic properties exhibit a noisy appearance. We demonstrate that this noisy appearance of the elastograms is due to the nonstationary relationship between the pre- and postcompression signals that results in an artifactual modulation of the strain estimates by the amplitude variations of the envelope of the rf signal. We have identified two methods to reduce the strain modulation artifact. The first method consists of reducing the signal amplitude swings within the observation windows by logarithmically or otherwise compressing the rf signal. The sensitivity of this method to amplitude compression strength and the ability to reduce the noise in the elastograms without affecting the spatial resolution are investigated through simulations. The second method to reduce the strain modulation artifact consists of temporal stretching of the signal obtained after physical compression to approximate the shape of the signal obtained before compression. In this paper, we discuss the first method. The results show that significant improvement in image noise can be obtained with logarithmic amplitude compression. This improvement is obtained in conjunction with improved spatial resolution. PMID- 8346614 TI - [Antagonistic activity of the rumen bacteria, Enterococcus faecium and Staphylococcus warneri]. AB - The bacterial strains E. faecium and S. warneri were tested for their antagonistic activities, and/or for the antimicrobial spectrum of bacteriocin like substances produced by these bacteria. Isolates of rumen and non-rumen origin were used as indicator strains (Tab. I). All the isolates (except the strains SW48 and EF24c as indicators of rumen origin) produced bacteriocin-like substances inhibiting the growth of at least one of the series of the nine indicators used while clear inhibition zones 2-10 mm prevailed (Tabs. II, III). Among the enterococci, the inhibition of non-rumen indicators was more intensive in comparison with the indicators of rumen origin, but the inhibition zones were only 2-5 mm. In general, the staphylococci showed the antagonistic activity with the lower antimicrobial spectrum in comparison with the enterococci. None of the tested strains inhibited the growth of the indicator E. faecium A26. The summary results show that the growth of both gram-positive and gram-negative bacteria was inhibited. The prolonged cultivation time did not influence the antagonistic activity of the tested strains. In the strains EF35, SW34 and SW98, the antagonistic activity was maintained after trypsin treatment. But in the other strains, this treatment led to the loss of the antagonistic activity. The use of pronase P resulted in the loss of the activity in the strains SW24, EF35 and EF26/142. The use of pronase P did not lead to the loss of the activity in the other tested isolates (Tab. IV).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346615 TI - [Long-term exposure to PCB in broiler chickens--metabolic and immunotoxic effects]. AB - Even though it has been forbidden to produce and commerically use polychlorinated biphenyls (PCB) in this country, their stocks and contaminated refuses continue to be a source of danger at present. Hence prevention of environment and food chain contamination is being focused on, along with their monitoring in various commodities. In the poultry operations random contacts of poultry with PCB containing materials may be expected (paints, plasters, litter). In our experiment we investigated metabolic and immunotoxic effects of low PCB doses on broiler chickens. A hundred and twenty sexed straight-run chicks randomly divided themselves into three departments on deep litter. Cockerels had an ad libitum access to feeds and water, and they were reared under a continuous lighting regime. A feed mix BR-2 (ME 12.8 i.u., crude protein 19.9%) was used as an experimental diet. The experimental groups received a contaminated mix (equal portions of original commercial PCB preparations--Delor 103 and Delor 105 manufactured by the firm Chemko Strazske) at doses of 5 and 50 mg/kg. Chick exposure to PCB lasted from the first to 42nd day of their life. Chick weight, relative organ weight and vitamin A and E levels in liver were determined at the end of the experiment (42 days). The concentrations of cholesterol, triglycerides, proteins, calcium and lysozyme were determined in the blood serum. The concentrations of antibodies to chick repeated immunization with a vaccine against Newcastle disease (AVIPEST) and the blood picture of chicks were also evaluated. Chronical PCB applications in broiler diet resulted in a significant decrease in the weight of broiler chicks at the age of 21 and 28 days (P < 0.01). The weight differences were compensated later on, and the chick weight of the different groups at the age of 42 days was not significantly affected by this treatment. Hepatitis and hydropericarditis were found in affected chicks at their dissection (age of 42 days). Liver weight significantly increased after administration of both PCB doses (P < 0.01), but the relative weight of lymphoreticular organs (thymus, spleen, bursa Fabricii) decreased (P < 0.05). There were serious metabolic disorders in the blood serum after 42-day PCB applications. Cholesterol and triglyceride concentrations (P < 0.01) were significantly increasing (P < 0.01), while the content of serum calcium significantly dropped (28 and 35 days of age). PCB exposed cockerels had the significantly lower titre of antibodies to repeated immunization against Newcastle disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8346616 TI - [Forms of xanthine oxidoreductase in the tissues of Japanese quail]. AB - The Japanese quail tissues--liver, kidney and pancreas were analysed for the presence of forms of xanthine oxidoreductase utilised cofactors NAD+, molecular oxygen or artificial acceptor--methylene blue, as well as for the validity of correlation between enzymatic activity and diet protein content. Four groups of animals with the experimental diets, the formulae of which are given in Tab. I, and control group with a commercial mash were fed for ten days. For enzyme preparation, the rough purification of cytoplasmic fraction with subsequent dialysis was used. The xanthine oxidoreductase utilised NAD+ (XOR-NAD) was detected in all examined tissues (Fig. 1), whereby the correlation of enzymatic activity with diet protein content was shown only in liver, according our previous findings (Jankela; 1978; Baranovska and Gazo, 1990). The values in liver and pancreas of animals fed a commercial mash were somewhat out of the range of linearity, probably because of the presence of nonprotein substances in mash, which affected the XOR activity in these organs (Jankela, 1992). The XOR utilised O2 (Fig. 2) was only detected in liver and kidney with certain activity in animals fed free protein diet. The percentage of this enzyme form was below 18% of the total activity (Fig. 5). The xanthine oxidoreductase utilised methylene blue (XOR-MM) was detected in liver, kidney and pancreas (Fig. 3). The correlation of enzymatic activity with diet protein content was linear in liver and kidney. The percentage of XOR-MM activity was very high, it amounted to 55% of the total activity (Fig. 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346617 TI - [The occurrence of avian mycobacteriosis in wild birds during various epizootic conditions of tuberculosis in poultry]. AB - The occurrence of tuberculosis in free-living birds was studied in relation to a certain epidemiological situation in a long-term study from 1966 to 1990. A total of 3210 birds were examined. Mycobacteria were isolated in five cases from free living birds in the environment of six poultry rearing farms where tuberculosis was found in domestic fowl. At individual localities, the occurrence of mycobacteria was 3.5-50.0%. Generalized tuberculosis was found in one case in house sparrow (Passer domesticus). On the investigated poultry rearing farms, the distribution of tuberculosis infection in free-living birds was directly related to the distribution and stage of tuberculosis in poultry or to the achieved extent of eradication. On a poultry rearing farm where no mycobacteria were isolated from free-living birds, a successful eradication of tuberculosis by flock exchange was in progress. During the examination of free-living birds on three farms, mycobacteria were found at two localities where poultry infected with tuberculosis was kept either on the farm or in its immediate vicinity. On the third farm, where no mycobacteria were found in free-living birds, only sporadic reactors to tuberculin were found during survey in spatially separated flocks. No mycobacteria were isolated from birds examined on two farms in whose vicinity poultry was not reared at all. Similarly, bacteriological cultures were negative in a group of 298 birds examined during five years in the environment of a poultry enterprise farm free from tuberculosis. No mycobacteria were found in a large group of 2303 free-living birds taken in the wild except four rooks (Corvus frugilegus). However, this is a migratory species which is noted for its considerable longevity. It is thus more probable that these birds were infected outside the locality which the specimens were taken from. Out of the isolated strains of mycobacteria that were further examined by a biological experiment, 86.6% were pathogenic to domestic fowl, serotype M. avium 2. The results of these examinations suggest that the presence of tuberculosis-infected poultry as a major source of M. avium is necessary for the infection of free-living birds. The infectious agent apparently does not persist and spread within the flocks of free living birds. PMID- 8346618 TI - [Steroid dominance, enzyme activity and morphological appearance of granulosa cells in the largest follicles in cows]. AB - The cyclic nature of the female reproduction process depends to a considerable degree on the unique capacity of ovarial follicles to change their structure and function. The differentiation process during folliculogenesis takes place in all parts of the follicle. Granulosa cells reflect a high degree of structural changes and play an important role in functional maturation of the inert follicle. Changes in the reaction to endocrine and paracrine effects from a unique environment that is inevitably necessary for oocyte growth and ovulation were reached by changes in the biochemical activity and the internal anatomic mutual relation of the follicle (Linder et al., 1976; Hsueh, 1976). This growth process and differentiation depend on gonadotropic stimulation of the follicles and the quantity of receptor sites able to bind them. The aim of this work was compare estradiol 17-beta and progesterone levels in the follicular fluid of the largest follicles with the morphological structure and enzymatic activity of membrana granulosa cells. Ovaries were obtained from 34 SS x LBS randomly chosen cows at the slaughter-house. Follicular fluid to estradiol 17-beta and progesterone level determination was obtained by aspiration of the largest follicles. Estradiol 17-beta and progesterone levels were determined by RIA sets from the URVJT (Institute of Radioecology and Use of Nuclear Techniques) in Kosice, type RIA-test-ESTRA (SI-125-129) and RIAA-test-Prog (SI-125-6), respectively. With the methods used the variation coefficient of intra- and interassay for the estradiol 17-beta of the RIA set were 10.1 and 13.3%, for progesterone of the RIA set these values were 11.4 and 13.7% respectively. Steroid dominance of follicles was determined by the method described by Callesen et al. (1986), based on the expression of the index of the mutual relation between progesterone levels and estradiol 17-beta was levels. Excisions from the follicular wall were examined under the scanning electron microscope JEOC 1200 Mx at an acceleration voltage of 20 kV. In granulosa cell smears acid phosphatase and non-specific esterase activity were determined by incubation in the incubation media according to Lojda et al. (1979). Steroid levels are given in nmol/l +/- SEM. Mean estradiol 17-beta levels in estrogen dominant follicles were proved to be 2170.0 +/- 1605.3 nmol/l, whereby individual concentrations ranged from 17.0 nmol/l to 10180.0 nmol/l.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8346619 TI - [The effect of bentazone, an herbicide produced in Czechoslovakia, on the invasiveness of intestinal nematodes in sheep]. AB - Possible anthelmintic effects of the Czechoslovak herbicide bentazone (Research Institute of Chemical Technology, Bratislava) on gastrointestinal tract strongylates of common occurrence were investigated in sheep of the Slovak Merino breed (housed on deep bedding and put out to grass daily) during the autumn and spring seasons. Our orientation to the investigation of anthelmintic effects of the mentioned herbicide resulted from the fact that its possible intervention in the energy metabolism of helminths could not be excluded, as it was indirectly indicated by our toxicological studies under the conditions of acute and subacute intoxication. Bentazone was administered at a dose of 250 mg/kg live weight in autumn and 500 mg/kg live weight in the spring season. It was administered per os as a single dose in sunflower oil. A control coprological examination on day 10 following the administration of the herbicide in question indicates the lower invasiveness of sheep in comparison with findings prior to its application (Tab. I) in both experiments (autumn, spring). No marked dose-dependent differences of bentazone efficiency were recorded. PMID- 8346620 TI - [Levels of total lipids, cholesterol and progesterone during estrus synchronization and pregnancy in sheep]. AB - Our investigations were concerned with dynamic changes in total lipids (CL), cholesterol (CHOL) and progesterone (P4) in blood serum of sheep in the period of oestrus synchronization treatment and during mating and gravidity. Our experiment was carried out using 10 animals housed under the conditions of productive rearing. Blood samples were taken from v. jugularis on day of swab application (day 0) and on days 3 and 7 of the action of Agelin vaginal swabs, on day of insemination, and on days 7, 14, 17 and in the 2nd, 3rd and 4th month of gravidity. Blood serum was used to determine total lipids and cholesterol by means of Bio-Lachema tests, and P4 concentrations employing RIA-test-Prog kits (URVJT, Kosice). A statistically significant decrease in concentrations of total lipids (Fig. 1, Tab. I) in sheep blood serum was recorded on day of insemination (P < 0.05) compared to day 0, with the value 1.59 +/- 0.31 g/l of serum, and in the 3rd month of gravidity (P < 0.01), at concentrations 1.36 +/- 0.38 g/l of serum. The determined decrease in their values in the mentioned period can be modulated by the mutually changing ratio of steroid hormones or by inhibition of synthesis of lipoproteins responsible for changes in total plasma lipids. Changes in cholesterol concentrations (Fig. 2, Tab. I) during the introduction of swabs were insignificant and ranged from 1.60 +/- 0.42 to 1.73 +/- 0.33 mmol/l of serum. An insignificant increase in cholesterol concentrations (P < 0.05), with its highest levels 1.98 +/- 0.43 mmol/l of serum, was recorded in the 3rd month of gravidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346621 TI - [Alkaline phosphatase during the puerperium in ewes and its relation to thyroid hormones and ovarian steroids]. AB - Triacylglycerols as the sources of cholesterol, the primary precursor of steroid synthesis, are one of the factors that limit the speed of steroidogenesis. Synthesis and resynthesis of triacylglycerols depend, in addition to other factors, on phosphatid hydrolysis that is controlled during pregnancy by placentary ALP (Sumikawa et al., 1987) and the FFA pool in the systemic blood stream. Enzymes participating in FFA release from the fat tissue are affected by thyroid hormones and TSH (Mayes, 1977). In view of the above facts, this work was aimed at the observation of changes in alkaline phosphatase (ALP), thyroxine (T4), triiodothyronine (T3), 17 beta-oestradiol (E2) and progesterone (P4) levels and their mutual correlations in the systemic blood stream of sheep from the first day after parturition to day 51 p.p. Our attention was paid to the possible delayed effects of placentary ALP and thyroid hormones on the synthesis of ovarian steroids in puerperal ewes. Nine merino sheep were included in the experiment; they lambed in the first decade of February and were kept together with their lambs in a classical sheep-cot on deep litter. The animals were fed according to the Czechoslovak State Standard CSN 46 7070. Blood samples were taken from the v. jugularis from 8 to 9 o'clock a.m. 24 hs (day -1) prior to parturition (a.p.), 36 hs and on days 4, 7, 14, 17, 21, 25, 34, 42 and 51 after parturition (p.p.). As compared with day -1 (2.6 +/- 1.08 mu kat/l), ALP concentrations showed a decrease with minimum values occurring on day 17 (1.34 +/ 0.97 mu kat/l, P < 0.05). T4 concentrations also decreased from day -1 (59.4 +/- 9.69 nmol/l) to day 21 (54.89 +/- 11.06 nmol/l, P < 0.05). A similar decrease (from 1.82 +/- 0.33 nmol/l on day 1 to 0.85 +/- 0.32 nmol/l on day 21) could also be observed in T3 levels. As early as 36 hs p.p., the concentrations of both steroid hormones, E2 and P4, significantly decreased [from 2.45 +/- 0.65 and 9.46 +/- 0.34 nmol/l on day -1 to 0.30 +/- 0.24 and 0.05 +/- 0.08 nmol/l, respectively (P < 0.001)]. Throughout the period of investigation, apart from an unsubstantial increase in E2 values on days 17 and 42 and an episodic increase in P4 levels on day 34, the concentrations of both steroids had the values that were significantly lower than those observed on day -1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8346622 TI - [Anthelmintic control of multiresistant nematodes in the gastrointestinal tract of imported goats]. AB - Multiple resistant strains of Ostertagia and Trichostrongylus were detected in a flock of cashmere and angora goats imported from New Zealand. The ED50 values detected by in vitro EHA test were from 0.27 to 0.36 micrograms/ml (while the reference value of sensitivity is 0.10 microgram/ml TBZ). Multiple resistance to all the types of currently used anthelmintics was confirmed by in vivo FECRT, when the efficacy of recommended doses was lower than 90% (albendazole 74%, levamisole 86%, ivermectin 83%). Two control schemes were investigated. In the simultaneous application of anthelmintics in the double or triple of recommended doses (0.4 mg/kg ivermectin s.c., 30 mg/kg levamisole and 20 mg/kg albendazole p.o.) was effective. Examination of goats 7 and 8 months after treatment revealed the repeated presence of multiple resistant gastrointestinal nematodes. It is the first published case of intercontinental transfer of resistant strains of nematodes when importing small ruminants. PMID- 8346623 TI - [Virologic detection of arboviruses in greater cormorants]. AB - Cormorants (Phalacrocorax carbo, Pelecaniformes) caught in southern Moravia (Czech Republic) in 1989-1990 were examined for arbovirus infections. Isolation experiments were carried out using blood samples of 56 birds. The results were negative. Serological examinations of 31 birds were performed by haemagglutination-inhibition test (HIT) using 5 arboviral antigens of the genera Alphavirus (Sindbis--SIN) and Flavivirus (tick-borne encephalitis--TBE, West Nile -WN) and of the family Bunyaviridae (Tahyna--TAH, Calovo--CVO). Antibodies were detected only to viruses SIN, WN and TAH at different frequencies: 9.7%, 9.7% and 22.6%. The titres ranged from 1:20 to 1:80. PMID- 8346624 TI - [The first finding of Giardia spp. in roebucks (Capreolus capreolus L.)]. AB - Roe deer (Capreolus capreolus L.) is a representative of the new host of an intestinal flagellate of the genus Giardia. Giardia spp. was found during autopsy in three dead head of roe deer (roe deer calf 7-8 months, doe, buck) sent for examination to the State Veterinary Institute, Praha, from three different localities of the Czech Republik. Localization of the Giardia spp. was studied in the intestinal tract of the roe deer calf in native preparations in the intestinal contents and in the smears of intestinal mucosa stained after Giemsa (at a distance of 30-40 cm along the whole length of the small intestine). Giardia trophozoites were found in the small intestine in the section of 280-770 cm from the caudal part of duodenum. The trophozoites occurred most intensively within the section of 350-420 cm. The trophozoites showed active, motility in this part of the small intestine as late as in more than 48 hours after the death of the row calf. Their size (obtained by measuring 30 trophozoites) was from 12.4 16.2 to 8-11.5 microns with the mean of 14.5 to 9.4 microns. In the contents of the caeca and colons of all three animals after death numerous Giardia cysts were found, in the caecum of the roe calf trophozoites were detected rarely. Most of the cysts were of ovoid shape. Their size, by measuring 50 cysts from each of the animals, was from 11.2-14.4 to 8-10.4 microns with the mean of 13.3 x 9.1 microns. Sporadically, nearly spherical cysts occurred (12.8-13.6 to 9.6-10.4 microns).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346625 TI - Special issue: Environmental impact of avermectin usage in livestock. PMID- 8346626 TI - Environmental effects of the usage of avermectins in livestock. AB - Abamectin (avermectin B1) and ivermectin (22,23-dihydroavermectin B1) are high molecular weight hydrophobic compounds, active against a variety of animal parasites and insects. Numerous environmental fate and effects studies have been carried out in the development of these two compounds as antiparasitic agents and for abamectin as a crop protection chemical. They were found to be immobile in soil (Koc > or = 4000), rapidly photodegraded in water (degradation half-life (t1/2) in the summer 0.5 days or less) and as thin films on surfaces (t1/2 < 1 day), and aerobically degraded in soil (ivermectin in soil/feces mixtures (t1/2) = 7-14 days; avermectin B1a in soils, t1/2 = 2-8 weeks) to less bioactive compounds. Abamectin is not taken up from the soil by plants, nor is it bioconcentrated by fish (calculated steady-state bioconcentration factor of 52, with rapid depuration). Daphnia magna is the fresh water species found to be most sensitive to ivermectin and abamectin (LC50 values of 0.025 and 0.34 ppb respectively); fish (e.g. rainbow trout) are much less sensitive to these compounds (LC50 values of 3.0 ppb and 3.2 ppb, respectively). In the presence of sediment, toxicity toward Daphnia is significantly reduced. The metabolism and degradation of ivermectin and abamectin result in reduced toxicity to Daphnia. Abamectin and ivermectin possess no significant antibacterial and antifungal activity. They display little toxicity to earthworms (LC50 values of 315 ppm and 28 ppm in soil for ivermectin and abamectin, respectively) or avians (abamectin dietary LC50 values for bobwhite quail and mallard duck of 3102 ppm and 383 ppm, respectively), and no phytotoxicity. Residues of the avermectins in feces of livestock affect some dung-associated insects, especially their larval forms. This does not delay degradation of naturally formed cattle pats under field conditions; however, in some cases, delays have been observed with artificially formed pats. Based on usage patterns, the availability of residue-free dung and insect mobility, overall effects on dung-associated insects will be limited. As abamectin and ivermectin undergo rapid degradation in light and soil, and bind tightly to soil and sediment, they will not accumulate and will not undergo translocation in the environment, minimizing any environmental impact on non target organisms resulting from their use. PMID- 8346627 TI - Effects of avermectin residues in cattle dung on dung beetle (Coleoptera: Scarabaeidae) reproduction and survival. AB - Scarabaeine dung beetles feeding on dung from cattle treated with an injection of avermectin at a therapeutic dose to control internal parasites, show larval mortality, mortality of immature adults, reduced egg production, and inhibited ovariole development for periods of 1-4 weeks following treatment. In winter rainfall regions of Australia, feeding by newly emerged adults of an introduced species, Onthophagus binodis, resulted in shredding of cattle dung between December and May. Production of brood masses and eggs resulted in dung being buried from September to November. Feeding by newly emerged adults of a native species, Onthophagus ferox, resulted in dung being buried in May and June, and production of brood masses for breeding resulted in dung burial between September and November. There are thus 2-6 months of the year when injection of cattle with avermectin would affect mortality of newly emerged beetles, and 3 months of the year when avermectin treatment of cattle would affect dung beetle oviposition or larval survival. Beetles were attracted to fresh dung for 2-4 days, and most had left the pad within a week. There are no data to indicate the effects of avermectin residues in dung on dung beetle populations and on beetle fitness. Tests should be done to determine if avermectins in slow release devices have a greater effect on dung beetles than injections, and to determine what effects both have on dung beetle populations. PMID- 8346628 TI - Effects of ivermectin residues in sheep dung on the development and survival of the bushfly, Musca vetustissima Walker and a scarabaeine dung beetle, Euoniticellus fulvus Goeze. AB - During produced by sheep for up to 1 week post-treatment (drenching) with ivermectin caused significant mortality to newly emerged larvae of the bushfly Musca vetustissima. Dung from sheep drenched with a mixture of levamisole and oxfendazole also resulted in larval mortality, but here the effect was limited to the first 48 h after treatment. Flies reared through to the adult stage on dung collected up to 32 days post-drenching were tested for evidence of fluctuating asymmetry, which is an indicator of developmental stress. None was found for either drench treatment, although there was evidence that ivermectin residues directly affected wing size. The introduced dung beetle, Euoniticellus fulvus was also found to be sensitive to ivermectin residues in sheep dung. Dung produced during the first day after drenching caused mortality among newly emerged beetles and delayed the reproductive development of survivors. However, beetles in which ovarian development was impaired regained their reproductive capacity following transfer to nontoxic dung. Day 1 dung caused no mortality among sexually mature beetles, although there was a significant reduction in their fecundity. Dung collected from 2 to 10 days post-drenching had no detectable effects on either the survival or reproductive development of adult beetles, regardless of age. Residues in dung collected 1-2 days post-drenching caused 100% mortality in beetle larvae, but by Day 5 there was no evidence of acute toxicity. These findings indicate that insects feeding on the dung of ivermectin-treated sheep display adverse effects similar in range to those reported for cattle dung. However, their duration is much more transient, owing probably to differences in drug formulation and route of administration. PMID- 8346629 TI - Attractiveness of dung from ivermectin-treated cattle to Danish and afrotropical scarabaeid dung beetles. AB - The effect of ivermectin treatment of cattle on the attractiveness of dung to scarabaeid dung beetles was assessed by pitfall trapping in Denmark, Tanzania and Zimbabwe. Traps were baited with dung collected at intervals after heifers were treated with ivermectin by subcutaneous injection (0.2 mg kg-1 body weight). In one Danish trial, beetles preferred control dung from untreated cattle, whereas no preference was found in two other experiments. In Tanzania, the overall tendency for beetles was also to prefer control dung. In Zimbabwe, two species (Euoniticellus intermedius and Liatongus militaris) were particularly attracted to dung from treated cattle, whereas three others did not discriminate between dung types. It is concluded that at least in some cases the attractiveness of cattle dung to scarabaeid beetles is affected by avermectin therapy. Beetle discrimination between dung types is probably attributable to some unknown side effect of the treatment rather than being a direct response to the drug itself. PMID- 8346630 TI - Effects of ivermectin on two afrotropical dung beetles, Onthophagus gazella and Diastellopalpus quinquedens (Coleoptera: Scarabaeidae). AB - Subcutaneous injection of 0.2 mg kg-1 ivermectin to heifers negatively affected larvae of the afrotropical dung beetles, Diastellopalpus quinquedens and Onthophagus gazella, developing in the dung. Although closely related, the two species seem to differ in susceptibility; 28% of brood masses made of dung voided 2 days after treatment contained third instar D. quinquedens, whereas O. gazella died as first instars in dung voided up to 8 days after treatment. Folding of the head capsules and lack of mandibular wear in the dead O. gazella larvae suggest that ivermectin could be absorbed through the integument and prevent normal feeding and distension of the head capsule. In addition, the surviving third instar O. gazella in dung voided 16 days after treatment had significantly reduced clypeal and mandibular widths. The dung burial activity, mainly by D. quinquedens, estimated in a field experiment was not affected by ivermectin residues in the dung. PMID- 8346631 TI - Some effects of ivermectin on the yellow dung fly, Scatophaga stercoraria. AB - Ivermectin was added to fresh cattle dung at a range of concentrations based on those found in faeces of livestock treated by injection. Newly hatched larvae of Scatophaga stercoraria were then reared in the dung as a bioassay. The EC50 values for 24 h and 48 h larval mortalities were 0.051 ppm and 0.036 ppm (wet wt.) respectively. When the dung concentration was 0.015 ppm, 50% of the insects failed to pupariate and a level of 0.001 ppm prevented adult emergence in 50% of the insects. When batches of larvae were reared in dung containing as little as 0.0005 ppm, the emerging adults showed developmental abnormalities in wing morphology. In addition to the significantly higher level of fluctuating asymmetry, 23% of the treated insects developed new veins and new cells in the wings. The observations are discussed in relation to previous work and attention is drawn to the practice of failing to observe the full impact of sublethal effects, which can be as serious as those of acute toxicity. PMID- 8346632 TI - A review of regional and temporal use of avermectins in cattle and horses worldwide. AB - Ivermectin and abamectin are two members of the group of parasiticides known as the avermectins; ivermectin was first registered as an injectable treatment for cattle in 1981. Since then, abamectin has been registered for cattle and ivermectin for horses. The relative popularity of the avermectins amongst farmers and veterinarians can be attributed to their spectrum of activity, convenience, wide margin of safety and the improved health and performance of stock following their use. Patterns of use in grazing animals apply equally to the avermectins as to other antiparasitics, particularly anthelmintics; these are based on a knowledge of epidemiology integrated with practical management considerations. For cattle, programs are commonly aimed at control of abomasal nematodes of the genera Ostertagia and Haemonchus. Use of avermectins is largely strategic in cattle, treatments being favored at the end of the period of transmission of these parasites; this frequently coincides with housing, entry into a feedlot or movement to another pasture. Simultaneous control of important ectoparasites at this time is an added benefit. Prophylactic use of avermectins at pasture is primarily targeted at the young first season grazing animal. In horses, a bimonthly treatment schedule during the period of risk has proved effective in helping prevent adverse effects of the main target parasites, including large and small strongyles and stomach bots. These patterns of use can be applied to the evaluation of the potential for avermectin residues in feces to have impact on pasture ecology. The evidence presented suggests that any effects are temporally and spatially limited. After more than a decade of practical use, there is no indication that avermectins have had a significant impact on pasture ecology and the environment. PMID- 8346633 TI - Reproductive development and survival of Lucilia cuprina Wiedemann when fed sheep dung containing ivermectin. AB - When fed dung from sheep treated with ivermectin 24 h previously, Lucilia cuprina adults exhibited reduced survival, delayed ovarian development and reduced egg production. These effects were absent in dung produced 2 or more days after ivermectin treatment. Such transient toxicity is ideal to restrict the evolution of resistance to this drug. This situation may change if the current practice of oral treatment is replaced by a slow-release system of administering avermectins. The avoidance of coincidental evolution of resistance is critical to the long term welfare of the Australian sheep industry as the avermectins represent an important, and as yet unexploited, insecticide for the treatment of flystrike caused by Lucilia cuprina. PMID- 8346634 TI - Effect of avermectin residues in sheep dung on mating of the Australian sheep blowfly Lucilia cuprina. AB - Male and female Lucilia cuprina adults were separated after emergence and then fed either dung excreted from sheep after an oral treatment with ivermectin (Ivomec) or non-treated sheep dung. Fresh dung (non-treated or ivermectin treated) was collected daily and fed to adults for 6 days after drenching. After this feeding period, males and females from each feeding treatment were paired and all aspects of mating behaviour recorded. Feeding on avermectin residues by adults had a significant effect on two components of mating: (1) males fed on ivermectin-treated dung directed less mating attempts at females compared with males fed on non-treated dung; (2) mating duration by males fed on ivermectin treated dung was longer compared with males fed on non-treated dung. There was no significant difference in the level of sexual receptivity (percentage mating) between females fed on either ivermectin-treated dung or non-treated dung, although subsequent oviposition by females fed ivermectin-treated dung was significantly delayed. Both female and male mortality was significantly greater when feeding on ivermectin-treated dung compared with non-treated dung. The effects on mating, when coupled with the deleterious effects on ovarian development and adult mortality, demonstrate the potential for avermectin usage in a control strategy against L. cuprina. PMID- 8346635 TI - The degradation of dung produced by cattle treated with an ivermectin slow release bolus. AB - Eight female calves of the Deutsches Fleckvieh breed, weighing 161-207 kg, were each treated at turnout on 16 May 1989 with one ivermectin sustained-release intraruminal bolus designed to release ivermectin at 12 mg day-1 for approximately 120 days. Eight animals remained as untreated controls. A third group of eight unmedicated tracer calves was not considered as part of this evaluation. All 24 animals grazed together on a single pasture throughout the study. On Days 21/22, 70 and 119, 15 faecal pats were selected from each treatment group and ranked according to surface area; within each group of three consecutively ranked pairs of pats, two pairs were randomly allocated as observation pats and the third as a sampling pat. The surface area of observation pats was measured, photographs taken, and dry matter, crude ash and organic matter determined at various intervals following deposition. A 1/4 sample collected from sampling pats 3, 7, 14 and 28 days after deposition was weighed and examined for Coleoptera (adults and larvae), Diptera larvae and nematodes. No differences between groups were seen in respect of organic matter content, numbers or frequency of adult Coleoptera species and soil nematodes. A decrease in numbers of Coleoptera larvae, Diptera larvae and dung-specific nematodes was observed in pats from ivermectin-treated cattle. Based on the evaluation of the surface area, a delay in the degradation rate of pats from treated compared with those from untreated animals was seen; however, the difference was statistically not significant (P > 0.05). PMID- 8346636 TI - Dung dispersal and grazing area following treatment of horses with a single dose of ivermectin. AB - Environmental consequences of treating horses with recommended dosages of ivermectin paste were studied in two controlled experiments with 29 horses in Ohio. In 1988, dung dispersal rates were measured by changes in dry weight over time of 48 copromes (300 g) formed from feces taken from four treatment and four control horses 3 days post ivermectin treatment. There was delayed dispersal of copromes from horses treated with ivermectin in June, resulting in significantly heavier ivermectin copromes compared with those of control horses by September. There was no difference in ivermectin or control copromes after treatment in August. In 1989, the effects of treating horses with oral ivermectin or oxibendazole compared with untreated controls were quantified in a study with 21 horses under natural grazing conditions after treatment on 7 June. Sequential measurements of dung pat circumferences from 20 June 1989 to 7 March 1990 showed highly significant differences between ivermectin and control pats and between ivermectin and oxibendazole pats. Reductions in mean dung pat diameters did not occur in ivermectin pats until 11 October, when there was a 4.1% reduction compared with 35.1% for control pats and 37.2% for oxibendazole pats. By the end of the study, there was a 24.7% reduction in ivermectin pats compared with 59.1% and 59.9% for control and oxibendazole pats respectively. In addition, there were significantly more pats showing complete dispersal in oxibendazole or control plots than in ivermectin plots. The calculated grazing area lost to feces was three times greater for ivermectin plots than for oxibendazole or control plots. It is suggested that environmental effects of the avermectins can be reduced by more rational use of anthelmintics. PMID- 8346637 TI - Ivermectin treatment of horses: effect on the distribution of lawns and roughs in horse pastures. AB - A study was carried out to assess the feasibility of determining the grazing patterns of horses bimonthly via aerial survey and standard cartographic techniques. The grazing patterns in pastures with equivalent stocking rates of horses treated bimonthly with 200 micrograms of ivermectin kg-1 or 10 mg of oxibendazole kg-1 was assessed using aerial survey mapping performed three times during a grazing season. The distribution patterns of lawns and roughs in pastures were similar at all times during the study. Aerial survey was determined to be a very efficient and objective method of determining the composition of pastures grazed by horses. PMID- 8346638 TI - Soil invertebrate/micro-invertebrate interactions: disproportionate effects of species on food web structure and function. AB - The preservation of biodiversity requires an appreciation of food web structure and an understanding of how disturbance alters their structure and function. Theoretical and empirical studies of food webs demonstrate that food webs possess a regular structure. Food chain length appears limited to three to four transfers, and, complexity and diversity are constrained. When ecosystem energetics are considered, species within food webs are seen to form interactive assemblages that process matter at different rates and respond to disturbance differently. Disturbance may affect the diversity of a system, or, may influence the relative importance of one species assemblage over another. Moreover, predicting the impact of disturbance on a system is difficult as species that comprise and process a small fraction of the system's biomass may control a disproportionate fraction of the system's biomass and diversity. Seven food webs at four sites were used in a modeling exercise to demonstrate this point. Field studies involving the role of mycorrhizal fungi yielded results consistent with the modeling studies as the types of plant species present, the level of production and the diversity of production were related to the levels of mycorrhizal fungi in the soils following disturbance. The results indicate that all species are important to ecosystem structure and function and that the monitoring of ecosystems and conservation efforts should expand their emphasis to the preservation of ecosystem integrity as well as that of individual species. PMID- 8346639 TI - The potential for avermectins to affect the nutrient economy of grazed pastures. AB - This examination of the potential ecotoxic effects of the avermectins in temperature pastures grazed by sheep is based on a community approach and is focussed on one important aspect of ecosystem function, the nutrient cycle. Data on the amount and distribution of sheep dung on pastures grazed at different stocking rates indicated that areas of high stocking and sheep camps would be affected by avermectin residues to the greatest extent. Mineral losses from sheep dung which does not contain ivermectin, have been examined to provide a background against which the potential effects of avermectins on nutrient cycling can be appraised. The source of the diet is important; for example, dung from sheep grazing on improved pasture loses sulphur faster, and has higher microbial activity, than that of native pasture, regardless of whether it is fresh or old. Dung-dwelling fauna such as dung beetles and microarthropods are most abundant in areas of high dung concentration and microbial activity is greatest in sheep camps where a large quantity of excreta is voided. However, while there is evidence that avermectin does affect certain of the larger dung-dwelling fauna, little is known of its effects on the smaller invertebrate biota such as free living nematodes and microarthropods. Calculations for phosphorus budgets on both native and improved pastures indicate that the amount of phosphorus recycled in these systems could be reduced by up to 5% the dosage levels currently recommended for the drug. PMID- 8346640 TI - The potential for avermectins to affect wildlife. AB - Avermectin residues in the dung from treated livestock are detrimental to dung insects. Rare insects could be put at risk by the use of avermectins, especially those which breed exclusively in the dung of the herbivores on which avermectins are used. Livestock dung is an important feeding habitat for a number of vertebrate species. The potential for direct poisoning of vertebrates through the accumulation of avermectins in the body, after consumption of invertebrates containing residues, would, on present knowledge, appear to be limited, but should not be disregarded. The use of avermectins may also indirectly affect some species of vertebrate by depleting the quality and quantity of important food resources. The effects of any reduction in invertebrate food in livestock dung would be expected to be especially severe if it occurred at critical times for the vertebrates, such as during the breeding season or when newly independent young animals were foraging and fending for themselves. Insects that develop in livestock dung therefore have important, additional roles in the ecology of pasture-lands, other than aiding dung degradation processes. It is essential that these other roles are taken into account when any assessment of the environmental consequences of using avermectins in livestock is being made. PMID- 8346641 TI - Environmental assessment of avermectins by the US Food and Drug Administration. AB - The Center of Veterinary Medicine (CVM) of the Food and Drug Administration (FDA) is required under the National Environmental Policy Act (NEPA) to include in its decision making, an objective consideration of the potential environmental impacts associated with each contemplated action. As part of the application process for new animal drugs, detailed data must be submitted in order to develop a prediction of the environmental fate and effects of the drug and/or its active metabolites. Ivermectin (22,23-dihydroavermectin B1) is a highly active antiparasitic animal drug utilized in a variety of injectable, oral and topical formulations. Residues of this drug may reach the environment through manufacturing and animal wastes and may potentially have effects on terrestrial and aquatic organisms. A comprehensive data base has been submitted to the FDA in support of the environmental assessments for ivermectin drug products. Detailed information has been submitted on the physical and chemical properties, introduction, fate and effects of the ivermectins in the environment. These data indicate that ivermectin binds tightly to soil and is subject to photodegradation and biotransformation to less active compounds. In contrast, ivermectin is highly toxic to certain aquatic organisms but would not be expected to partition into the aquatic environment. Much lower toxicity has been demonstrated toward bacteria, fungi, earthworms, plants and birds. CVM evaluated ivermectin products based on the use pattern of the product, the metabolism pattern in target animals, calculations of potential ivermectin residue concentrations in the environment and data on persistence, soil sorption and acute toxicity in aquatic and terrestrial environments. PMID- 8346642 TI - Regional and temporal use of avermectins for ruminants in Australia. AB - The avermectin class of anthelmintics has been available for approximately 4 years (sheep) and 7 years (cattle) in Australia. They are highly efficacious against a very broad spectrum of nematode parasites and certain ectoparasites of livestock. To date there are no field reports of resistance to these compounds in either the cattle or sheep industry, despite the fact that nematode parasites of sheep show high levels of resistance to other broad spectrum anthelmintics. The avermectins have gained rapid acceptance, but their share of the anthelmintic market is less than expected, owing to several factors such as drought and recession of the rural economy. Nevertheless, it can be expected that this class of compounds will assume greater importance, particularly in the sheep industry, when greater awareness of the widespread failure of alternative broad spectrum anthelmintics, and the value of regional worm control programs become accepted by producers. PMID- 8346643 TI - Towards sustainable nematode parasite control of livestock. AB - Farmers worldwide have come to expect, and rely almost exclusively on, broad spectrum anthelmintics to effectively control nematode parasites amongst their livestock. However, the threats of resistance, residues and ecotoxicity are of increasing concern to the future of chemotherapy. It is imperative that sustainable parasite control schemes be developed and implemented which will integrate a range of techniques to minimise anthelmintic use and still maintain high levels of profitability of the farming enterprise. At present, these need to focus on the better use of existing drugs to maximise their effectiveness and minimise the selection for resistance and impact on the environment. New drugs should also be used according to these principles. In the future it is expected that other non-chemotherapeutic options will become available, e.g. helminth vaccines, resistant hosts, biological control, nematode growth regulators, which will revolutionize the current thinking on nematode parasite control of livestock. PMID- 8346644 TI - Overview: the impact of avermectins on pastureland ecology. AB - Avermectins, a relatively new class of broad spectrum pesticides, are used widely to control livestock parasites. Following treatment, avermectins are eliminated in the livestock faeces where they also have a wide range of harmful affects upon certain characteristic insects that breed in dung, few of which are pests, and many of which are beneficial. The effects range from acute toxicity in larvae and adults, through disruption of metamorphosis, to interference with reproduction. Different methods of drug administration lead to different concentrations of drug residues in the faeces, which in turn influence the responses of non-target organisms. Higher Diptera are particularly sensitive to drug residues and show a wide range of responses from death of larvae to developmental abnormalities in the adults. Larvae and immature adults of Coleoptera show some mortality in the dung of recently treated animals, while delayed effects upon reproduction and physiology have been observed in adults feeding on dung at longer post-treatment times. Although the impact of lethal doses has been described in some species, the effects of sub-lethal doses have hardly been recognised at the present time. Correlated with the deleterious effect upon dung-breeding insects, a retardation in the rate of loss of biomass of dung pats from avermectin-treated cattle has been observed following the various forms of drug administration. Differences in methodology, inappropriate statistics, and/or extremes of climatic conditions prevailing at the time of testing, explain the results of those studies where such delays have not been observed. It is short-sighted to consider only dung dispersal in relation to avermectin usage, a practice that overlooks the impact on the insects themselves and their diverse roles in pastureland ecology. PMID- 8346645 TI - Biological control of nematode parasites in cattle with nematode-trapping fungi: a survey of Danish studies. AB - In Denmark two series of experiments have been performed to study the interactions between larvae of bovine gastrointestinal nematode parasites and nematode-trapping fungi. For practical reasons we were interested in the possibility of depositing nematode-trapping fungi in cattle faeces after passage through the gastrointestinal tract. In the first series, laboratory tests with the fungus Arthrobotrys oligospora showed that motile free-living larvae of a wide range of animal-parasitic nematodes and some soil-living nematodes effectively induce the formation of traps. Larvae of all parasitic nematodes are rapidly captured in these traps. The induction of nets was influenced by temperature, number of larvae, atmosphere, light, and media composition. Captured first- and second-stage larvae were quickly penetrated and killed while third stage larvae were killed slowly, perhaps because they are partially protected by an outer dead sheath. Laboratory and field studies showed that when A. oligospora material was directly mixed into dung a significant reduction in the number of infective parasite larvae in the dung and surrounding herbage occurs. This reduction was also reflected in the acquired worm burden of calves grazing on fungal treated pasture. However, the A. oligospora strain studied in the above mentioned experiments did not survive passage through the alimentary tract of cattle. This prompted us to start a second series of experiments to isolate fungi that could survive gut passage of cattle. Different soil and compost samples were screened by an in vitro stress selection technique. This simulated certain important stress factors which occur during passage through the alimentary tract of ruminants. Rumen exposure was found to be a major limiting factor, but some Arthrobotrys and Duddingtonia strains survived submersion in rumen fluid. In a subsequent in vivo experiment, some of these survivors were fed to calves, and it was hereby demonstrated that isolates of both genera, i.e. Arthrobotrys and Duddingtonia, were able to survive passage through calves and significantly reduce the number of developing preparasitic larvae in dung of fungal treated calves. In a controlled field experiment, isolates of Duddingtonia reduced the level of infective third-stage larvae in herbage by 74-85%. PMID- 8346646 TI - Control strategies for ruminant and equine parasites to counter resistance, encystment, and ecotoxicity in the USA. AB - The need for improved parasite control strategies to conserve anthelmintic efficacy and to avoid drug-related problems are addressed. Recent surveys have revealed a trend for sole dependence on ivermectin by livestock owners in the USA, with little regard for epidemiologic-based strategies, or the annual rotation of unrelated anthelmintic groups. Innovative parasite control strategies for cattle, sheep, and horses in northern USA are presented. The importance of closer monitoring and more rational use of anthelmintics is stressed. PMID- 8346647 TI - Research recommendations. AB - Delegates met on the final morning to identify areas where information is lacking and to highlight priority areas for future research. Five principal topics were discussed: veterinary usage, methodology, invertebrate populations, agricultural impact and integrated pest management. PMID- 8346648 TI - Pharmacokinetics and metabolism of avermectins in livestock. AB - The kinetics of avermectin disposition and metabolism in ruminant livestock and horses are reviewed with particular emphasis on the influence of route of administration and formulation on persistence of residues in tissues and excretion in faeces. Because information is not publicly available on other compounds in this class currently under development (e.g. moxidectin, doramectin), ivermectin only is considered. The biological half-life of ivermectin in plasma is similar in cattle and sheep but because of a larger volume of distribution, plasma clearance is more rapid in sheep. However, injection of the subcutaneous formulation of ivermectin prolongs plasma residence time and persistence of drug residues particularly in liver and fat. Increasing the organic solvent content of subcutaneous formulations slows the release of drug from the injection site and thereby prolongs its presence in the bloodstream. Because ivermectin and its metabolites are mainly excreted in bile, residues continue to appear in faeces for substantially longer following subcutaneous injection than after oral dosing. Aqueous based injectable formulations in cattle may therefore reduce the impact of ivermectin treatment on dung fauna. Binding of avermectins to digesta particulates during gut transit may potentially lower drug bioavailability and also contribute to faecal residues. Further research on formulation and dosage strategies is advocated to increase bioavailability at the gastrointestinal site of action so that both dose rate and faecal residues can be reduced. PMID- 8346650 TI - Changes with time after treatment in the concentrations of ivermectin in fresh cow dung and in cow pats aged in the field. AB - An analytical procedure for detection of ivermectin in plasma samples was modified and used for measuring ivermectin concentrations in dung samples. The residues were quantified by high-performance liquid chromatography and fluorescence detection after extraction, purification, and derivatization into fluorescent reaction products. The concentrations of ivermectin in dung were measured after dosing heifers with 0.2 mg kg-1 by subcutaneous injection or 0.5 mg kg-1 by pour-on. Despite the 2.5 times higher pour-on dose, this formulation did not result in excretion of detectable concentrations of ivermectin over a longer period of time than did the injection treatment. Dung pats with ivermectin residues were exposed on grazing pastures until they were no longer colonised by flies and beetles. In the experiments performed under temperate and tropical conditions, the aging of the pats did not lead to a significant lowering of the concentrations of ivermectin. Flies or beetles colonising the pats some time after deposition may therefore not be exposed to decreased levels of ivermectin. PMID- 8346649 TI - Chemical assay of avermectins by high performance liquid chromatography with fluorescence detection. AB - Chemical methods for determining the concentrations of the avermectins in feeds, dosage forms, and biological samples are reviewed. The earliest methods for measuring the avermectins made use of the intense ultraviolet absorption due to the conjugated diene (olefinic bonds between carbons 8 and 9 and carbons 9 and 10) that has an ultraviolet absorption maximum at 245 nm and a molar absorptivity of over 30,000 l mol-cm-1. High performance liquid chromatographic (HPLC) separation of the avermectins and photometric measurement of their absorption at 245 nm has permitted the determination of plasma or serum concentrations to approximately 10 ng ml-1. Increased sensitivity of detection has been achieved by dehydration of the dihydroxycyclohexene ring of the avermectins in the presence of various catalysts that produces an intensely fluorescent derivative with an absorption maximum at 365 nm and emission maximum at 475 nm. These derivatives have been separated by HPLC and detected by fluorescence detectors at concentrations less than 1.0 ng ml-1 of plasma or serum. Recent improvements in the use of more efficient catalysts to effect the dehydration have reduced analysis time and decreased the formation of by-products, thereby improving the performance of these methods. A method based on HPLC with fluorescence detection of the dehydrated derivative was developed to determine ivermectin in horse dung after oral ivermectin doses of 200 micrograms kg-1 of body weight. Ivermectin concentrations greater than 0.05 microgram g-1 of wet feces were detectable for 1 2 days after dosing. PMID- 8346651 TI - Assessment of disturbance on soil ecosystems. AB - Given the complexity of ecosystems, the high degree of interactions among species, and the numerous responses of systems to disturbance, it is unlikely that simple assays developed for other systems would adequately serve to monitor soil systems. Apart from the questionable applicability of non-soil techniques, protocols to monitor soil biota in a standardized manner have not been developed. To monitor soils, a five-phase plan is proposed. The plan involves: (1) a thorough survey of the systems biota; (2) laboratory toxicity trials on indicator species (Folsomia candida); (3) field tests on indicator processes (litter decomposition); (4) field monitoring of indicator functional groups (nematodes); (5) the development of standardized statistical techniques and simulation models. Each phase of the plan was designed to capture a different aspect of food web structure and function. PMID- 8346652 TI - Methods for assessing the impact of avermectins on the decomposer community of sheep pastures. AB - This paper outlines methods which can be used in the field assessment of potentially toxic chemicals such as the avermectins. The procedures focus on measuring the effects of the drug on decomposer organisms and the nutrient cycling process in pastures grazed by sheep. Measurements of decomposer activity are described along with methods for determining dry and organic matter loss and mineral loss from dung to the underlying soil. Sampling methods for both micro- and macro-invertebrates are discussed along with determination of the percentage infection of plant roots with vesicular-arbuscular mycorrhizal fungi. An integrated sampling unit for assessing the ecotoxicity of ivermectin in pastures grazed by sheep is presented. PMID- 8346653 TI - Importance of methodology in the interpretation of factors affecting degradation of dung. AB - Many factors affect dung degradation and colonization, including the location, composition, moisture content, weight, surface area and organic matter content of dung pats. Because of the number and variability of these factors, methodology plays a major role in studies using the dung pat as an experimental unit. For results of such studies to be meaningful, conditions should be standardized as much as possible and the sampling technique should be systematic and consistent. This paper reports the results of experiments or trials which pay particular attention to aspects of methodology. PMID- 8346654 TI - The strategy for treatment of helminth infections in domestic ruminants. PMID- 8346655 TI - [In memory of Professor Bronislaw M. Honigberg]. PMID- 8346656 TI - [Coccidiosis of rabbits and its control]. AB - The investigations were performed on 6 farm rabbitries in Wroclaw district. Average extensiveness of coccidia infection was 95%, while intensity ranged from 50 to 408,700 ocysts/g of faeces. Nine species of coccidia were identified. Eimeria perforans (84.5%) and E. stiedai (73.2%) dominated, E. coecicola was noticed most seldom (20.7%). In young rabbits up to 3 months of life the infections were caused by 5-9 species of coccidia. However, in animals from breeding herd there prevailed infections caused by 1-3 species. Congeneric infections were stated very rarely, i.e. in 5.7% of infected animals only. Dynamic changes in the intensity of coccidia infections in rabbits in the course of one year breeding cycle on one of the farms demonstrated the occurrence of two peaks in females used for reproduction: the first one in the perinatal period and the second one in the period preceding weaning. The letter one, higher than the first one, was caused by keeping young rabbits with mothers for 8-10 weeks. The studies on the effectiveness of anticoccidial drugs were carried out on California White rabbits (age 5-7 weeks), infected naturally with 9 species of coccidia. Rabbits were given for 5 weeks the following anticoccidials: lasalocid (Avatec), maduramycin (Cygro), robenidine (Cycostat), salinomycin (Sacox), monensin (Elancoban), clopidol + methylbenzoquate (Lerbek) and narasin (Monteban). The best results were obtained with salinomycin at the dosages of 35, 50, 25 ppm and maduramycin at 2 and 3 ppm. Equally effective, but characterized by lower production indices, were: clopidol + methylbenzoquate (216.7 ppm), lasalocid (90, 125 ppm) and monensin (20 ppm). Robenidine was very effective against intestinal coccidia at the dose of 66 ppm, however it had weak effect on E. stiedai's infection. Narasin and maduramycin (4.5 ppm) had toxic effect on animals. A field trial (anticoccidials applied for 6 weeks in does and their progeny) confirmed high effectiveness of salinomycin (25 ppm), maduramycin (1.5 ppm) and monensin (20 ppm). PMID- 8346657 TI - [Histochemical estimation of lipid amounts in cells of the hepato-pancreatic gland of Lymnaea stagnalis (L.) (Gastropoda, Pulmonata) naturally infected with digenetic larvae]. AB - Acid and neutral lipids in epithelial cells building tubules of the digestive gland of snails naturally infected with digenetic larvae were stained with nil blue sulphate. Strong decrease in number of phospholipids granules in secretory cells, as well as in calcium cells in the infected glands was observed. The larvae caused also decrease of number of neutral lipids in both types of cells, but these changes were much smaller and did not refer to small granules laying in top parts of the epithelial cells. Changes in number of lipids granules were limited only to the cells of tubules damaged by parasites. PMID- 8346659 TI - [Bird trematodes of lower Silesia. IV. Specimens from the genus Mosesia (Pleurogenidae, Trematoda)--new element of parasitic-fauna passeriform birds from lower Silesia]. AB - Illustrated descriptions of Mosesia pavlovskii, M. sittae and M. microsoma have been presented. These species have been described for the first time in Poland, and two of them--M. sittae and M. microsoma--have not been know in Europe until now. Motacilla flava, Turdus philomelos and T. merula are new hosts of these trematodes. M. sittae has been recognized as an autochthonous species--completing its life cycle in the climatic conditions of Lower Silesia. As for the other two species, the author supposes that their invasion has been connected with the birds' migrations or wintering. PMID- 8346658 TI - [Processes connected with hatching of larvae from eggs of parasitic nematodes]. AB - Influence of such factors as temperature, pH, CO2 level and oxidation- reduction potential value in the alimentary tract of host on the stimulation of invasive eggs was studied. Changes of these factors lead to change in permeability of inner layer of egg-shell. Then the hatching fluid is released and its enzymes digest the egg-shell. In the nematodes, which have the free-living larvae, the initiation process can depend on parasite or environmental agents. PMID- 8346660 TI - [Fecunditiy and reproductive activity of Argas (A.) reflexus (Fabricius, 1794) (Acari: Ixodida: Argasidae) under laboratory conditions]. AB - Fecundity and reproductive activity of 179 females of Argas (A.) reflexus in laboratory conditions, i.e. at temperature 23 +/- 1 degree C and 75% of relative humidity were observed. Under these conditions reproduction activity of females fed in spring lasted since March till August. However, most of females (63.0 91.8%) laid eggs in June and July. Disturbances in egg-laying process of Argas (A.) reflexus females fed in abnormal time, i.e., in autumn and kept in laboratory conditions, were stated. These females were active since December till July (maximum activity was observed in February-34.3% and March-40.0%). Pre oviposition and oviposition periods were observed in this study, too. PMID- 8346661 TI - Canestriniid mites (Acari, Astigmata, Canestriniidae) occurring on chrysomelidae (Insecta, Coleoptera) in neotropical region. II. Genera Ovarrothiana n. gen., Ennodithiana n. gen. AB - Two genera Ovarrothiana, Ennodithiana and 10 species are described as new: Ovarrothiana nikodemi from Peru, Brazil, O. erazmi from French Guiana, Brazil, O. ozannae from Peru, Brazil, Ecuador, O. ludomiri and O. leopoldi from Bolivia, Ennodithiana messalinae from Costa Rica, Cuba, E. maniusi from Brazil, Mexico, E. penelopae from Surinam, Brazil, E. medoni and E. megesi from Brazil. PMID- 8346662 TI - Responses of immune sheep to challenge and the periparturient egg rise. PMID- 8346663 TI - Haemonchus contortus: a challenging parasite from immunological point of view. PMID- 8346664 TI - Exchangeable body potassium as an in vivo indicator of changes in body composition of calves exposed to natural infection with gastrointestinal nematodes. PMID- 8346666 TI - Immunosuppression during infections with adult tapeworms. PMID- 8346665 TI - Effect of diet in immunity and local immune responses of rabbits to Obeliscoides cuniculi. PMID- 8346667 TI - The epidemiological situation of parasite infections in wild ruminants. PMID- 8346668 TI - The epidemiological situation of gastrointestinal nematode infections in domestic ruminants. PMID- 8346669 TI - The sequence of hepatitis E virus isolated directly from a single source during an outbreak in China. AB - In this study an IgM antibody-mediated antigen-capture procedure for direct extraction of hepatitis E virus (HEV) RNA from clinical specimens was developed and used with an efficient method for generating viral cDNA that was subsequently sequenced using the dideoxy chain termination method. This is the first time the complete HEV genome has been isolated directly from a single human clinical specimen obtained during an outbreak of enterically transmitted non-A, non-B hepatitis. When the Chinese-derived sequence was compared with the original isolate of Burmese HEV from an experimentally infected cynomolgus macaque, the homology between the two sequences was 94% and 98.5% at the nucleotide and amino acid levels, respectively. The methods we developed for generating and sequencing genomic HEV cDNA dramatically improved the efficiency of cloning the viral genome and should be helpful for continued analysis of this virus as well as other RNA viruses that have proven to be difficult to clone and sequence directly. PMID- 8346670 TI - The gene encoding the late nonstructural 36K protein of vaccinia virus is essential for virus reproduction. AB - Two genetic markers--the thymidine kinase gene of herpes simplex virus, and the beta-galactosidase gene of Escherichia coli--were incorporated into the 36K protein gene (IL1 gene according to the nomenclature of the Copenhagen strain of vaccinia virus; Goebel et al., 1990) from the HindIII-P DNA fragment of the LIVP strain (variant of Lister strain) of vaccinia virus (VV). After recombination of the obtained integration plasmid pVZ64-TK with the VV genome (tk-), it was found that the resultant TK+ viruses were unstable with respect to the Lac+ phenotype. On the basis of hybridization of DNA fragments of selected clones, a scheme for the formation of hybrid viruses is proposed, and an approach to a simple phenotypical discrimination between essential and non-essential genes for VV viability is described. PMID- 8346671 TI - The complete nucleotide sequence of African horsesickness virus serotype 4 (vaccine strain) segment 4, which encodes the minor core protein VP4. AB - The complete sequence of RNA segment 4 of African horsesickness virus serotype 4 (AHSV-4) vaccine strain was determined from the full-length cDNA clone inserted into pBR322. The RNA is 1978 bp long (M(r) 1.27 x 10(6)) and contains an open reading frame encoding a protein of 642 amino acids (M(r) 75826) with a net charge of +10 at neutral pH. The 5' and 3' termini of AHSV-4 segment 4,5'GTTTAT... and ...CCTTAC3', were different from orbivirus characteristic terminal sequences, being 5'GTTAAA... and ...ACTTAC3'. A comparison of the sequence of AHSV-4 segment 4 with that of bluetongue virus (BTV) serotype 10 revealed 55.4% nucleotide similarity and 48.5% amino acid similarity. In addition, Northern blot hybridization showed that the full-length AHSV-4 segment 4 cDNA cross-hybridized well with the corresponding genes of serotype 1, 2, 3, 4 and 7 but slightly with serotype 5, 6 and 8 of attenuated AHSV. PMID- 8346672 TI - Expression of HIV-1 nef in yeast: the 27 kDa Nef protein is myristylated and fractionates with the nucleus. AB - The nef gene of human immunodeficiency virus type 1 (HIV-1) has been expressed in the yeast Saccharomyces cerevisiae to produce native Nef proteins. The proteins of M(r) 27 kDa and 25 kDa, produced by translation from the first and second start codons of the nef gene react with human HIV-1 antisera. Under low-level steady-state expression conditions, Nef27 undergoes myristylation and is targeted to the nuclear fraction while Nef25 is not myristylated and not nuclear localized. When produced rapidly and to high levels, Nef27 is initially present in the cytoplasm as a soluble myristylated protein that later fractionates with the nucleus. PMID- 8346673 TI - Alteration of cell population structure due to cell lysis in Saccharomyces cerevisiae cells overexpressing the GAL4 gene. AB - Transformed Saccharomyces cerevisiae cells overexpressing the Escherichia coli LacZ gene and the transcriptional activator GAL4, release in the external medium a fraction (from 2 to 10%) of the total beta-galactosidase activity (Porro et al., 1992b). It is known that this abnormal release of a cytoplasmic protein is related to a partial cell lysis of the yeast population, which is likely to be caused by the overexpression of the transcriptional activator GAL4. In the present paper we have characterized the GAL4-induced cell lysis phenomenon. The expression of the GAL4 gene causes morphological modifications and alteration of the cell size distribution. The cell lysis is independent of the expression of the heterologous LacZ gene and occurs in a specific subpopulation of cells (the parent cells) independently of the genealogical age, growth phase conditions and cell cycle progression. Lysis is preceded by a loss of the plasma membrane integrity as indicated by the uptake of ethidium bromide in unfixed cells. Computer analysis of simulated protein distributions indicates that cell lysis takes place in a sizeable aliquot (about 50%) of the parent cells, therefore profoundly altering the age structure of the population. PMID- 8346674 TI - Known heat-shock proteins are not responsible for stress-induced rapid degradation of ribosomal protein mRNAs in yeast. AB - We have previously shown that the heat-induced enhanced decay of yeast mRNAs encoding ribosomal proteins (rp-mRNAs) requires ongoing transcription during the heat treatment [Herruer et al. (1988) Nucl. Acids Res. 16, 7917]. In order to determine whether this requirement reflects the need for heat-shock protein (hsp), we analysed the effect of heat shock on rp-mRNA levels in several yeast strains in which each of the heat-shock genes encoding hsp26, hsp35 or hsp83 had been individually disrupted. In all three strains we still observed increased degradation of rp-mRNAs immediately after the temperature shift, demonstrating that hsp26, hsp35 and hsp83 are not required for this effect. Accelerated turnover of rp-mRNA was also found to occur upon raising the growth temperature of a mutant strain that contains a disruption of the gene specifying the heat shock transcription factor and in wild-type yeast cells treated with canavanine, an arginine analogue that will be incorporated into all known hsps and that is known to cause misfolding of the polypeptide chain. Latter observation suggests that enhanced rp-mRNA decay is a more general stress-related phenomenon. Taken together, these data strongly indicate that the trans-acting factor required for the increase in the rate of degradation of rp-mRNAs upon stress is not one of the known yeast hsps. PMID- 8346675 TI - Absence of cell wall chitin in Saccharomyces cerevisiae leads to resistance to Kluyveromyces lactis killer toxin. AB - Kluyveromyces lactis killer toxin causes sensitive strains of a variety of yeasts to arrest at the G1 stage of the cell cycle, and to lose viability. We describe here the isolation and characterization of a class of recessive mutations in Saccharomyces cerevisiae that leads to toxin resistance and a temperature sensitive phenotype. These mutant cells arrest growth at 37 degrees C with a characteristic phenotype of elongated buds. Cloning of the gene complementing these defects revealed it to be CAL1, coding for chitin synthase 3 activity. Calcofluor staining of the mutant cells indicated that chitin is absent both at 23 degrees C and 37 degrees C. Given that the CAL1 activity is responsible for the synthesis of most of chitin in yeast cells, and that in its absence the cells are viable but resistant to the killer toxin, our results strongly suggest that chitin might represent the receptor for this killer toxin. PMID- 8346676 TI - A new promoter-probe vector for Saccharomyces cerevisiae using fungal glucoamylase cDNA as the reporter gene. AB - A system is described for the selection of DNA sequences showing promoter activity in the yeast Saccharomyces cerevisiae using a heterologous reporter enzyme which is efficiently secreted by the yeast host. A multicopy shuttle plasmid of the YEp-type was constructed so as to carry multiple unique cloning sites at the 5' end of the Aspergillus awamori glucoamylase cDNA. Glucoamylase can only be expressed upon insertion at one of these unique cloning sites of a DNA fragment from any source, provided it is endowed with promoter function in S. cerevisiae. As the glucoamylase signal-peptide is functional in S. cerevisiae, the enzyme is efficiently secreted by the yeast transformants. This phenotype can be very easily detected on plate assays and accurately quantified by spectrophotometric analysis of the culture supernatant. Since S. cerevisiae naturally lacks amylolytic activity, any wild-type strain can be used as a host in this system. To evaluate the system, a DNA pool of random fusions was created by ligating sau 3A digested S. cerevisiae genomic DNA to the BglII-linearized vector. The resulting hybrid plasmids were transformed into S. cerevisiae and several transformants secreting glucoamylase to varying degrees were obtained. PMID- 8346677 TI - Assay of trehalose with acid trehalase purified from Saccharomyces cerevisiae. AB - An enzymatic end-point assay of trehalose using acid trehalase from yeast is described. After quantitative hydrolysis of trehalose by acid trehalase, the resulting glucose is assayed with the commercially available glucose oxidase/peroxidase dye system. Pre-existing glucose is determined in a control reaction from which acid trehalase is omitted. When intact cells are analysed for trehalose, pre-existing glucose can be washed out with ice-cold water without reducing the trehalose content of the cells. A convenient method for extraction of trehalose from intact yeast cells is heating for 20 min at 95 degrees C followed by centrifugation. The specificity of the assay is determined by the specificity of the acid trehalase preparation used. As described previously (Mittenbuhler, K. and Holzer, H., 1988, J. Biol. Chem. 263, 8537-8543; Mittenbuhler, K., 1988, Thesis, University of Freiburg), the following sugars and sugar derivatives do not form glucose when incubated with purified acid trehalase: sucrose, cellobiose, mellobiose, raffinose, maltose, lactose, glucose 6-phosphate, glucose-1-phosphate, galactose. The application of the new trehalose assay to yeast cells grown to different growth stages and at various temperatures is presented. PMID- 8346679 TI - Expression of the glucose oxidase gene from Aspergillus niger in Hansenula polymorpha and its use as a reporter gene to isolate regulatory mutations. AB - The glucose oxidase gene (god) from Aspergillus niger was expressed in Hansenula polymorpha using the methanol oxidase promoter and transcription termination region and the MF-alpha leader sequence from Saccharomyces cerevisiae to direct secretion. The expression cassette was cloned into the S. cerevisiae vector YEp13 and used to transform H. polymorpha strain A16. In the initial transformants plasmid replication was unstable, but was stabilized by a growth regime consisting of alternating cycles of selective and non-selective growth. The stabilized strain was grown to high cell density by fed-batch fermentation. Upon induction of the MOX promoter, glucose oxidase synthesis was initiated. At the end of the fermentation, the culture density was 76 g dry weight/1 and 108 IU/ml (0.5 g/1 or 0.65% dry weight) glucose oxidase was found in the culture medium; a further 86 IU/ml (0.43 g/1 or 0.56% dry weight) was recovered from the cell lysate. A plate assay was used to monitor glucose oxidase levels in individual colonies. This was then used to isolate mutants which showed abnormal regulation of god expression or which showed an altered pattern of secretion. One mutant, which showed increased production of glucose oxidase, was grown to high cell density by fed-batch fermentation (100.6 g/l) and produced 445 IU/ml(2.25 g/l or 2.2% dry weight) extracellularly and 76 IU/ml (0.38 g/l or 0.4% dry weight) intracellularly. The mutant thus not only increased total production but exported 83% of the total enzyme made compared to 55% in the parent strain. PMID- 8346678 TI - Molecular analysis of HEM6 (HEM12) in Saccharomyces cerevisiae, the gene for uroporphyrinogen decarboxylase. AB - HEM6 (HEM12) in Saccharomyces cerevisiae encodes uroporphyrinogen decarboxylase, the fifth enzyme in the heme biosynthetic pathway. The HEM6 (HEM12) gene was cloned by complementation of heme auxotrophy of a hem6 mutant. Sequence analysis revealed an open reading frame of 1086 nucleotides. The predicted amino acid sequence of HEM6 (HEM12) shows extensive homology to those reported for uroporphyrinogen decarboxylase from mammalian sources. Expression of HEM6 (HEM12) was investigated and was found to increase two-fold in a non-fermentable carbon source. However, HEM6 (HEM12) transcription was unaffected by heme or by intermediates in the heme biosynthetic pathway. In addition, HEM6 (HEM12) expression is not regulated by the transcriptional activator complex HAP2-3-4, as has been shown for some genes encoding heme biosynthetic enzymes. PMID- 8346680 TI - Purification and characterization of aminopeptidase yspI from Schizosaccharomyces pombe. AB - Aminopeptidase yspI was purified to apparent homogeneity from the fission yeast Schizosaccharomyces pombe. The molecular mass of the native enzyme was estimated to be 184 kDa by gel filtration chromatography. A value of 92 kDa was calculated after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is thus a dimer with two identical subunits. Optimum pH for cleavage of synthetic aminoacyl-4-nitroanilides is 7.0. Mercury ions, EDTA and chloroquine were found to be potent inhibitors of aminopeptidase yspI activity. Substrate specificity studies indicate that the purified enzyme cleaves L-lysine-4-nitroanilide with high efficiency. PMID- 8346681 TI - RIM2, MSI1 and PGI1 are located within an 8 kb segment of Saccharomyces cerevisiae chromosome II, which also contains the putative ribosomal gene L21 and a new putative essential gene with a leucine zipper motif. AB - We report the DNA sequence of an 8 kb segment localized on the right arm of chromosome II from Saccharomyces cerevisiae. The sequence reveals the presence of eight open reading frames (ORFs). Three of them, YBR1402, YBR1405 and YBR1406 are previously sequenced genes, respectively the RIM2 (replication in mitochondria), MSI1 (multicopy suppressor of IRA1 gene) and PGI1 (phosphoglucoisomerase) genes. The predicted product of the ORF YBR1401 could be the putative yeast ribosomal protein L21. A new essential gene, YBR1403, has been identified by disruption; it possesses a leucine zipper motif. PMID- 8346683 TI - Cloning and sequencing of the URA3 gene of Kluyveromyces marxianus CBS 6556. AB - The URA3 gene, coding for orotidine-5'-phosphate decarboxylase, from Kluyveromyces marxianus CBS 6556, was isolated from a genomic DNA library. The K. marxianus URA3 gene encodes a protein of 267 amino acids with a calculated molecular weight of 29.3 kDa. Comparison of the K. marxianus protein with the corresponding enzymes of Saccharomyces cerevisiae and Kluyveromyces lactis showed amino acid sequence identities of 81% and 88%, respectively. Using contour clamped homogenous electric field gel electrophoresis, the genomic copy was found to be located on chromosome VI. We have used the cloned gene for the construction of a K. marxianus leu2 mutant. This mutant contains no heterologous sequences, which is essential to make it acceptable for application in the food industry. PMID- 8346682 TI - Para-aminobenzoate synthase gene of Saccharomyces cerevisiae encodes a bifunctional enzyme. AB - The Saccharomyces cerevisiae gene for para-aminobenzoate (PABA) synthase has been identified based upon its ability to confer sulfonamide resistance when present on a multicopy episomal vector. The 3840 bp DNA sequence fragment reported here contains a 2199 bp open reading frame encoding a 733 amino acid protein with similarity to the two components of PABA synthase described for prokaryotes (Escherichia coli PabA and PabB), suggesting that PABA synthase is bifunctional in yeast. The cloned sequence was confirmed to be PABA synthase by gene disruption. Chromosome gel analysis places the gene for PABA synthase on chromosome XIV. PMID- 8346684 TI - [Leg lengthening using callotasis. 2. Evaluation of a group of patients with surgical treatment, discussion, literature]. AB - In part 2 of the article the authors evaluate a group of 45 completed cases of lengthening of long bones, using the method of consecutive distraction according to Ilizarev. On average a lengthening of 5.4 cm was achieved. The authors evaluate the procedure of lengthening, the period taken by therapy in relation to the patients' age. The mean period of treatment was 5.7 weeks per 1 cm lengthening and it depends distinctly on the patient's age. In a total of 16 patients at the same time also correction of the axis of the leg was made. A major part of the investigation is devoted to evaluation of complications which, consistent with the literature, are classified as major, requiring further surgery, and minor ones which can be resolved without surgery during the lengthening procedure. Major complications were recorded 9 times, minor ones 8 times. Only in one instance the lengthening was terminated before the planed distraction was achieved. The authors evaluate these complications in relation to the length of distraction, the patient's age and the time when the lengthening was performed. At the same time they give instructions how to prevent complications and how to deal with them, if they arise. The conclusions and evaluation of the group of patients are dealt with in a detailed discussion where the authors compare their results with extensive references in the literature. PMID- 8346685 TI - [Locked nailing of fractures of the long bones. 1. Fractures of the leg]. AB - The authors present an account of their initial experience with the use of a method of locked nailing of fractures of the leg, applying the technique described by Grosse and Kempf. They use original implants of Howmedica Co. They indicated for osteosynthesis closed fractures of the leg in the middle three fifths of the bone length, without major damage of soft tissues (grade 0 and 1 of Tscherne's classification). In injuries with imminent compartment syndrome they operated after a delay, in all others they operated early after injury. Using the described method, the authors operated 16 patients. In three instances they used static locking of the nail, in 13 instances dynamic locking. The authors did not observe any delayed healing of the fractures. The only complication was partial paresis of the deep branch of the peroneal nerve. In all instances the patients were allowed to weight-bearing of the operated extremity soon--on average 3.5 weeks after operation. Recovery followed after 8-15 weeks. The authors consider this method with regard to the possible functional treatment, stability for weight-bearing, and rapid recovery of the fracture as the optimal therapeutic procedure for almost all types of closed fractures in the middle three fifths of the leg. PMID- 8346686 TI - [Complications after replacement of a knee joint endoprosthesis with a cementless "low contact stress" prosthesis]. AB - Total endoprosthesis of the knee joint of the LCS type reduce due to the mobile placement of the menisci and rotatable components the mechanical demands on anchoring in bone and thus contribute to satisfactory biological integration. During the period between June 1, 1989 and December 31, 1991 in the orthopaedic department of the general hospital in Zwettel 41 patients had 42 total endoprostheses (LCS) of the knee joint implanted. The group comprised 34 women and 7 men. All patients were checked and evaluated according to Hungerdorf's schema. The age range was 62 to 79 years with an average of 65.8 years. The follow-up period was 8 to 38 months, mean 21 months. The results as regards pain, stability, mobility, axis of the extremity and ability to walk were evaluated as very good and good. The authors discuss also postoperative complications. They did not observe loosening of cement-free components. PMID- 8346687 TI - [Technical problems in reoperation of hip joint prostheses]. AB - At the Orthopaedic Clinic of the Institute for Postgraduate Medical Training in the course of 10 years (1979-1989) 2340 primary implantations of total endoprostheses of the hip joint were performed. During the same period 168 total endoprostheses of the hip joint and 20 cervico-occipital prostheses were reoperated. The most frequent reason for reoperation was aseptic loosening of the acetabular component. The mean period between operation and reoperation in these patients was 98 months. In the group with loosening of the socket associated with mechanical destruction of the component the mean period which had elapsed since the primary operation was 43 months. In 87% small size sockets were involved. The most serious problem of reoperation of total endoprostheses of the hip joint is replacement of bone defects. During reoperation of acetabular components an isolated defect on the floor of the acetabulum was found in 26%, a defect of the margins in 38% and a combined defect of the margins in 26% of the patients. For treatment of the defects the authors used bone grafts in the majority allogenic grafts were involved which were used to reconstruct the margins and floor of the acetabulum. Metal implants should hold the bone grafts in the desired position and should not serve as a skeleton. Reoperation of the acetabular part of total endoprostheses of the hip joint is easier from the technical aspect; in defects of the upper portion of the femur it is essential to use a very careful procedure and to preserve the skeleton to a maximal extent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346688 TI - [Autofixation of the transposed tibial tuberosity in habitual patellar dislocation]. AB - Habitual luxation of the patella is as a rule considered an indication for a stabilizing operation. As regards approaches to the surgical solution of this problem we can differentiate between operations of the proximal part of the extension apparatus, i.e. operations of the soft tissues and operations on the distal part of the extension apparatus, above all plastic operations and transposition of the insertion of the lig. patellae on the tuberositas tibiae. In the present paper the authors submit their own modification of transposition of the tuberositas tibiae, suitable in severe affections after closure of the epiphyseal space. The described technique makes it possible to anchor the transposed tuberosity by an autofixation mechanism without using osteosynthetic material. The basis of the method is removal of a small block of bone with the insertion of the lig. patellae, size 2 x 4 cm, and its insertion beneath the corticalis at a site selected in advance into an opening 2 x 2 cm with subsequent covering and stitching of the periosteum. The extent of medialization depends on testing during flexion and extension. To prevent the development of the syndrome of patellar hyperpression it is important to avoid excessive distalization of the insertion of the ligament. During the preoperative period it is recommended to apply a plaster splint for two weeks, followed by functional rehabilitation and gradual burdening; complete burdening should be attained by the third month after operation. The surgical technique was tested in a group of 16 patients at the First Orthopaedic Clinic and with regard to its simplicity and reliability the method can be recommended. PMID- 8346690 TI - [Rehabilitation after total endoprosthesis replacement of the hip joint]. AB - The authors present an account on the rehabilitation programme used in patients after total endoprostheses, as practiced in their department. They draw attention to the importance of mutual collaboration of doctors and rehabilitation instructors. Without it even the best surgical operation would not produce the desirable effect. They also draw attention to the advantages of remedial exercise before operation and the necessity to start with remedial exercise immediately after surgery and continue after discharge from the hospital. In the conclusion they outline some problems they encountered during their work with patients after total endoprostheses. PMID- 8346689 TI - [Revitalization of bone transplants using vascular implants]. AB - For investigation of revascularization of free autogenous bone grafts by implantation of blood vessels the authors used rats as experimental material. The arteries or bundles of arteries were implanted into the spongiosa of the free bone transplant--a tall vertebra. It was revealed that capillary proliferation which promotes revascularization of the graft started in the adventitia of the implanted artery. Therefore it is not necessary to severe the artery, as recommended in methods used in previous studies. Revascularization occurs even when the implanted artery retains its original function. Implantation of blood vessels does not prevent extensive necrosis of the graft but indicates osteogenesis which results in substitution of the necrotic tissue. PMID- 8346691 TI - [Dual x-ray absorptiometry in the diagnosis of osteoporosis]. AB - The author presents a review providing information on contemporary modern radiological possibilities as regards the diagnosis of osteoporosis at the First Orthopaedic Clinic in Bratislava. At present this department possesses a densitometer LUNAR DPX-L. This apparatus assesses the bone density on the basis of double X-ray absorption. The software available at present makes it possible to assess the bone density of the lumbar spine in the anterio-posterior and lateral projection, as well as the proximal femur and whole body. The mean time required for assessment is 4 mins. 24 secs. to 16 mins. 30 secs. The mean radiation load of the patient is 1.5 mrem, the maximal load 3.5 mrem. The apparatus compares the assessed density values with mean values of the healthy population, it evaluates automatically statistical values of the Z and T score. These results are presented either as a coloured graph or as values of bone mineral density and bone mineral content. The author explains in more detail the principle of modern densitometry and its development during the past three decades. PMID- 8346692 TI - [Arteriovenous aneurysm--an uncommon complication in open fractures of the leg]. AB - The authors describe a less common complication of external osteosynthesis--a false arteriovenous aneurysm. On the case-history of a patient they demonstrate the risk associated with insertion of nails, the necessity of careful follow-up of patients after operation, and in case of suspicion, the necessity of accurate diagnosis and urgent surgical operation. PMID- 8346693 TI - Abuse in the workplace: a symptom that signs alone won't cure. PMID- 8346694 TI - Choosing nursing--an Edmonton perspective. PMID- 8346695 TI - The role of nursing research in the development of a knowledge base for practice. PMID- 8346697 TI - Holistic nursing. Reflexology. PMID- 8346696 TI - Boston: an education experience. PMID- 8346698 TI - Screen test Alberta. After the NBSS: has anything changed? PMID- 8346699 TI - Pain corner. The substance abuser with chronic malignant pain: nursing approaches. PMID- 8346700 TI - Health information: nursing components. PMID- 8346701 TI - Relationship between nursing practice and the practice of other health care professionals. PMID- 8346702 TI - [Reversible dementia and polyneuritis in an elderly woman: a case of late-onset disseminated lupus erythematosus]. AB - Reversible dementia and polyneuropathy in an elderly woman: a case of late onset systemic lupus erythematosus. We report the case of a 76-year-old woman with undiagnosed systemic lupus erythematosus. She presented with severe dementia. She was given prednisolone 20 mg daily with dramatic improvement occurring within one month. Electrophysiological study showed evidence of axonal neuropathy. PMID- 8346703 TI - Intranasal caffeine and amphetamine causing stroke. AB - A 37 year-old man with an ischaemic stroke after the nasal use of amphetamine and caffeine is reported. Transient arterial hypertension due to these agents may have been the mediator of the stroke. Mitral annular calcification was the only other abnormality found, and was thought not to play an important role in this patient. There was no evidence of a primary or secondary hypercoagulable state. Stroke due to nasal use of these agents appears not to have been previously reported (Medline literature search 1983-1993). PMID- 8346704 TI - Function of proteoglycans in the extracellular matrix. AB - Proteoglycans are glycosylated proteins which have covalently attached highly anionic glycosaminoglycans. Many forms of proteoglycans are present in virtually all extracellular matrices of connective tissues. The major biological function of proteoglycans derives from the physicochemical characteristics of the glycosaminoglycan component of the molecule, which provides hydration and swelling pressure to the tissue enabling it to withstand compressional forces. This function is best illustrated by the most abundant proteoglycan in cartilage tissues, aggrecan. During the past decade, diverse species of proteoglycans have been identified in many connective tissues, on cell surfaces and in intracellular compartments. These proteoglycans have distinct biological functions apart from their hydrodynamic functions, and their involvement in many aspects of cell and tissue activities has been demonstrated. For example, decorin, which is widely distributed in many connective tissues, may have functions in regulating collagen fibril formation and in modifying the activity of transforming growth factor beta; perlecan, the major heparan sulfate proteoglycan in the glomerular basement membrane, may play an important role as the major anionic site responsible for the charge selectivity in glomerular filtration. Specific interactions between proteoglycans (through both their glycosaminoglycan and core protein components) and macromolecules in the extracellular matrix are the key factors in the functions of proteoglycans. Exciting biological functions of proteoglycans are now gradually emerging. PMID- 8346705 TI - Consultations in surgical pathology. Association of Directors of Anatomic and Surgical Pathology. PMID- 8346706 TI - Immunohistochemical and ultrastructural characterization of autoimmune sialoadenitis in aging BDF1 mice. AB - To further the understanding of the immunopathologic mechanisms involved in spontaneous autoimmune sialoadenitis of aging BDF1 mice, immunohistochemical and ultrastructural studies were undertaken. Eighteen of 19 aging BDF1 mice, 23-27 months of age, developed sialoadenitis spontaneously. By light and electron microscopy, it was observed that the submandibular gland lesion was characterized by mononuclear cell infiltration in the periductal and perivascular areas often accompanied by parenchymal destruction. Immunohistochemically, T cells predominated. The ratio of CD4+ to CD8+ T cells ranged from 0.5:1 to 2.9:1, with an average of 1.4:1. It seems likely that not only CD4+ cells, but also CD8+ cells, play a major role in submandibular gland inflammatory reactions of aging BDF1 mice. PMID- 8346707 TI - Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy. AB - The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non uniform progression of massive fibrosis, which is closely related to small arterial lesions. PMID- 8346708 TI - Cell-cycle analysis detecting endogenous nuclear antigens: comparison with BrdU in vivo labeling and an application to lung tumors. AB - The versatility of non-radioactive cell-cycle analysis in detecting endogenous nuclear antigens of the proliferating cells was evaluated. Optimal conditions for immunostaining varied in fixation and pretreatment procedures among antigens, bromodeoxyuridine (BrdU), Ki-67 epitope, DNA polymerase alpha and PCNA. A significant correlation between BrdU labeling index (LI) was observed in each positive ratio (PR, positive/total neoplastic cells) for nuclear antigens in tumor-sections which had been labeled in vivo with BrdU. The best correlation was observed in Ki-67 PR (y = 1.26x + 2.5; y = Ki-67 PR; x = BrdU LI; r = 0.97). To determine its prognostic value, Ki-67 analysis was applied to the surgically resected lung tumors. Ki-67 PR were different according to the histologic types of the tumors: 47.8 +/- 3.4% in small cell carcinoma; 29.5 +/- 3.5% in squamous cell carcinoma; 28.3 +/- 4.7% in large cell carcinoma; 15.2 +/- 1.8% in adenocarcinoma and 0.1 +/- 0.1% in mature carcinoid tumor. When the mean value was used to divide each type to a higher or lower proliferative activity (15% Ki 67 PR for adenocarcinoma and 30% for squamous cell carcinoma), the group with the lower Ki-67 PR showed a significantly more favorable prognosis than that of a higher ratio. Ki-67 PR was not correlated with other pathologic factors such as size, lymph node metastasis or pleural involvement. Non-radioactive cell-cycle analysis was feasible and useful for detecting endogenous nuclear antigens even in the lung tumors, particularly when the analysis was coupled with histologic typing. PMID- 8346709 TI - Early stage of development in testicular choriocarcinomas. AB - Choriocarcinoma is the most malignant among germ cell tumors in the testis. However little is known about the early stage of its development. To understand the development of testicular choriocarcinomas, twenty cases of testicular choriocarcinoma were studied histologically and immunohistochemically. It was found that in the early stage of development, choriocarcinomas imitate the morphologic or functional differentiation of normal trophoblasts. It was also found that some choriocarcinomas regress spontaneously in the early stage. The majority of choriocarcinomas seemed to develop by first going through the embryonal carcinoma phase. However, there were some choriocarcinomas that showed no relationship with embryonal carcinoma. PMID- 8346710 TI - Protein-losing enteropathy due to secondary amyloidosis of the gastrointestinal tract. AB - A case of a 71 year old woman who experienced weight loss, diarrhea and edema due to protein-losing enteropathy caused by amyloidosis secondary to rheumatoid arthritis is described. Amyloid deposits were found in the systemic organs, specifically in the bowel. The arterioles were massively involved within the laminae propriae and many were narrowed considerably due to amyloid deposits. Ulcerative lesions, which were accompanied with the ruptured arterioles, were also found. Lymphangiectasia was present in the submucosa, subserosa and mesenterium. The mesenteric lymphatic vessels were deposited markedly with amyloid. The principal cause of the protein loss might be related to the increased capillary permeability to plasma proteins and the exudation through an inflamed mucosa. Functional disruption of the lymphatic flow in the bowel and mesenterium might also participate in the mechanisms of the protein loss. Evidence in this study supports the theory that lymphatic disorders in some patients with gastrointestinal amyloidosis are one of the important factors in the pathogenesis of protein-losing enteropathy. PMID- 8346711 TI - Myxoma of the breast: report of a case with unique histological and immunohistochemical appearances. AB - A case of myxoma of the breast is reported. The patient, a 19 year old Japanese woman, showed a lump in the left breast which had enlarged gradually over 3 years. A tumor measuring 5 x 5 x 4.5 cm was located mainly in the mammary parenchyma, but partially involved the overlying subcutaneous tissue. Histologically the tumor was multinodular and each nodule consisted of an abundant myxoid substance with a few spindle or stellate mesenchymal cells. The presence of hyaluronic acid was observed in the myxoid area, and a few constituent cells showed immunoreactivities for S-100 protein and alpha 1 antichymotrypsin. Electron microscopic studies revealed that some constituent cells looked like undifferentiated mesenchymal cells, while others showed a differentiation similar to fibroblast or histiocyte. These findings suggest that the constituent cells might derive from totipotential primitive mesenchymal cells. PMID- 8346712 TI - Mistletoe (viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review. AB - Therapy of cancer with a Viscum extract has been carried out in Europe for over six decades in thousands of patients with uncertain advantages. This approach has been bedeviled by major problems such as variable composition of the extract, lack of knowledge of active component(s) and mechanism of action, to cite a few. However the recent standardization of Viscumin in terms of galactoside-binding lectin activity has allowed to clarify that it can act as powerful inflammatory mediator able to stimulate the immune system. Merits and demerits of this approach have been reviewed and although the active component has probably not unique immunoenhancing properties, it may be useful as an adjuvant in the biological therapy of cancer and it should not be ignored any longer. As usual, medical progress depends upon experimentation and not exclusively on intuition and emotion. PMID- 8346713 TI - Cytokine regulation of iron metabolism: effect of low-dose interleukin-2 subcutaneous therapy on ferritin, transferrin and iron blood concentrations in cancer patients. AB - It is known that the anemias of chronic diseases, which often occur in neoplastic and in systemic inflammatory disorders, are characterized by high levels of ferritin associated with generally low iron concentrations, by suggesting an iron transfer defect due to unknown factors. Since both chronic inflammatory diseases and advanced neoplasms are characterized by alterations in the endogenous production of cytokines, a possible involvement of interleukins in chronic disease-related anomalies of iron metabolism cannot at present be excluded. The present study was carried out to investigate the effect of low-dose IL-2 subcutaneous immunotherapy (3 million IU/day for 6 days/week for 4 weeks) on ferritin, transferring and iron serum levels in cancer patients. Six patients with metastatic gastrointestinal carcinomas were evaluated. Ferritin mean levels significantly decreased during IL-2 treatment, and this finding was associated with a significant increase in transferrin values. Iron mean levels increased in response to IL-2, without, however, significant differences in respect to the pretreatment concentrations. These preliminary data, by showing changes in ferritin, transferrin and iron in cancer patients during the immunotherapy with IL-2, would suggest the existence of a cytokine regulation of iron transfer from tissues to blood, perhaps by modulating the macrophage function. PMID- 8346715 TI - Generalized occurrence of the broadly antiviral substance UTI beta in mammalian sera. AB - This study compares the characteristics of naturally occurring antiviral activities in nonhuman mammalian sera to UTI beta (University of Texas virus inhibitor beta), an innate, non-specific viral inhibitor found in human serum. The antiviral agent in sera from four different species appears to possess properties similar to those of UTI beta, e.g. molecular weight of 60 +/- 10 kDa, broad spectrum antiviral activity, glycoprotein structure with antiviral oligosaccharide moiety(s) attached to a carrier protein, and inhibition of most viruses by preventing their attachment to target cells. These findings suggest that UTI beta or UTI beta-like virus inhibitors are a normal component of the non specific immune defenses of mammals. PMID- 8346714 TI - Amplification of eosinophilia by melatonin during the immunotherapy of cancer with interleukin-2. AB - Eosinophilia, which occurs during IL-2 immunotherapy, has appeared to be due to an enhanced secretion of IL-5 and to be associated with a clinical response. Since our previous experimental studies showed that the pineal hormone MLT potentiates IL-2 efficacy, a study was started to evaluate the influence of a concomitant MLT administration on IL-2-induced eosinophilia. The study included 30 advanced solid tumor patients, 16 of whom received IL-2 alone (6 million IU/day) and the other 14 IL-2 plus MLT (10 mg/day orally at 8.00 P.M.). Eosinophil mean number was significantly enhanced during both treatments, but its increase in patients receiving IL-2 plus MLT was significantly higher than that seen in patients treated with IL-2 alone. These results show that MLT may enhance IL-2-induced eosinophilia, by suggesting that T helper lymphocyte- type 2, which is the source of IL-5, may be the target cell for MLT action. PMID- 8346717 TI - Unraveling the function of the retinoblastoma gene. PMID- 8346716 TI - Cancer prevention research trials. PMID- 8346718 TI - Oncogenic basis of radiation resistance. PMID- 8346720 TI - Molecular approaches to cancer therapy. PMID- 8346719 TI - Molecular genetic changes in human breast cancer. PMID- 8346721 TI - Regulation and mechanisms of mammalian gene amplification. PMID- 8346722 TI - Clinical pharmacokinetics of sotalol. AB - Sotalol is an antiarrhythmic agent with combined class II and III properties. It is nearly completely absorbed after oral administration and undergoes essentially no first-pass hepatic metabolism. As a result, its absolute bioavailability is 90 100%. Peak plasma concentrations are reached 2-4 hours after an oral dose. Administering sotalol with food reduces its bioavailability by approximately 20%. A 2-compartment model adequately describes the decline of sotalol plasma concentrations after intravenous or oral administration. The drug has an apparent volume of distribution of 1.2-2.4 liters/kg. Results of animal studies indicate that sotalol distributes into a number of tissues, including those of the heart, liver, and kidney, but it is hydrophilic and thus penetrates the central nervous system poorly. Sotalol does not bind to plasma proteins. No significant biotransformation of sotalol takes place in humans. Sotalol is primarily eliminated by renal excretion, with approximately 80-90% of a dose being excreted unchanged in the urine; a small amount is excreted unchanged in the feces. In subjects with normal renal function, total body clearance of sotalol averages 150 mL/min and the terminal elimination half-life is 10-20 hours. Long-term administration of sotalol does not alter its kinetics, and plasma concentrations following single or multiple doses are proportional to the dose. Sotalol is a racemic mixture of the d- and l-stereoisomers. d,l-Sotalol is excreted in the urine equally as d- and l-sotalol, and there is no evidence of racemization. The clearance of sotalol is reduced and its elimination half-life is prolonged in patients with renal insufficiency; as a result, dosage adjustment is necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346723 TI - Pharmacologic basis of the antiarrhythmic and hemodynamic effects of sotalol. AB - Sotalol is a competitive beta adrenoceptor antagonist devoid of membrane stabilizing activity and intrinsic sympathomimetic activity that has no preferential actions on beta 1 or beta 2 responses. No other tested receptor systems are affected by sotalol. In addition to having class II (beta blockade) effects, sotalol also has class III antiarrhythmic activity. It increases the action potential duration (APD) and prolongs atrial and ventricular repolarization. The effect on APD is independent of beta blockade; the same effect is seen with similar concentrations of the d stereoisomer of sotalol, which does not have beta-blocking activity. Sotalol prolongs the rate-corrected QT interval and ventricular and atrial refractoriness without affecting atrial, His-Purkinje, or ventricular conduction velocity. Atrioventricular nodal conduction is decreased, largely because of beta blockade. Sotalol increases the fibrillation threshold and decreases the defibrillation threshold. Sotalol is an effective antiarrhythmic in various animal models of arrhythmia (e.g., chloroform, hydrocarbon-catecholamine, ouabain, and coronary ligation). In addition, it reduces the severity and frequency of arrhythmias induced by programmed electrical simulation. By comparison, metoprolol is ineffective and d sotalol is as effective as the racemate in this model, indicating that this effect is independent of beta blockade. Sotalol causes concentration-dependent increases in the contractility of isolated ventricular tissue that is not blocked by previous beta or alpha blockade or catecholamine depletion. The positive inotropic effect may be related to inhibition of time-dependent K+ current responsible for the increase in APD. Like propranolol, sotalol decreases contractile force, heart rate, arterial blood pressure, left ventricular dP/dt, and cardiac output in intact animals due to blockade of circulating catecholamines. Sotalol consistently reduces the heart rate to a greater degree than propranolol and causes significantly less cardiac suppression than propranolol at a given heart rate. PMID- 8346724 TI - Indications for antiarrhythmic suppression of ventricular arrhythmias: a definition of life-threatening ventricular arrhythmias. AB - A surprising finding of the Cardiac Arrhythmia Suppression Trial (CAST), reported in 1989, is that well-tolerated and effective antiarrhythmic drugs may also be associated with an increase in mortality due to arrhythmia. Consequently, attention has been focused on the importance of the benefit-versus-risk assessment of such therapy. The benefits of antiarrhythmic therapy are reduction or elimination of arrhythmia-caused symptoms (both hemodynamic and nonhemodynamic) and of the associated risk of death. The risks of such treatment include not only noncardiac adverse effects and organ toxicity, but also early cardiac effects (proarrhythmia, heart failure, and conduction defects), as well as the newly recognized potential for late proarrhythmia or late arrhythmic death. Unfortunately, as the potential benefits of antiarrhythmic therapy increase in patients with poorer left ventricular function (owing to their being at greater risk for sudden death), the effectiveness of suppression decreases and the incidence of life-threatening complications increases. The impact of this benefit-risk profile is that the indication for most currently approved antiarrhythmic drugs needs to be limited to those patients with definite life threatening ventricular arrhythmias that take the form of sustained ventricular tachyarrhythmias with associated hemodynamic symptoms. Broadening this indication to include patients with probable life-threatening or even possible life threatening arrhythmias must await the availability of drugs with better benefit risk profiles. PMID- 8346725 TI - Effect of oral sotalol on systemic hemodynamics and programmed electrical stimulation in patients with ventricular arrhythmias and structural heart disease. AB - We explored the central hemodynamic responses to oral sotalol during dose titration in patients with ventricular arrhythmias who underwent programmed ventricular stimulation. Twelve patients were included in the study, 9 with a history of sustained ventricular tachyarrhythmias (6 postmyocardial infarction and 3 with cardiomyopathy) and 3 with a history of nonsustained ventricular tachycardia postmyocardial infarction. Left ventricular ejection fractions were < 45% in 10 patients, and < 35% in 5; the mean ejection fraction was 37% (range 20 51%). Sotalol prevented the induction of ventricular tachycardia in each of 3 patients with nonsustained ventricular tachycardia and in 6 of 9 with sustained ventricular tachycardia at baseline study. At peak action (2 hours) after sotalol loading (mean dose, 167 mg orally twice daily), the hemodynamic effects included bradycardia, decreased cardiac index, increased left ventricular filling pressure and systemic vascular resistance, and no change in stroke volume or stroke work index. One patient was not continued on sotalol, owing to an excessive increase in the pulmonary capillary wedge pressure, despite the lack of symptomatic heart failure. Congestive heart failure in association with marked bradycardia developed in another patient, who had suppression of inducible ventricular tachycardia after sotalol loading; this patient was managed with a reduction in the dose of sotalol and a regimen of digoxin and furosemide, and has been well compensated and without a recurrence of sustained ventricular tachycardia for more than 4 years. Ventricular tachycardia has been controlled with sotalol, without hemodynamic deterioration, in 6 of these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346726 TI - Clinical safety profile of sotalol in the treatment of arrhythmias. AB - The safety of sotalol was evaluated in 3,257 patients treated for cardiac arrhythmias in double-blind and open-label clinical trials that support United States registration of the drug. In this composite population, 80% of patients had structural heart disease and 42% had life-threatening ventricular arrhythmias, i.e., ventricular tachycardia (VT) or fibrillation (VF). Proarrhythmia was reported in 141 patients (4.3%). Of these, 78 (2.4%) had torsades de pointes and 26 (0.8%) had sustained VT or VF. The overall incidence was higher in patients treated for sustained VT or VF (6.5%). In these patients, serious proarrhythmia was predominantly torsades de pointes (4.1%) and was more prevalent in patients with congestive heart failure and low ejection fraction. Torsades de pointes was observed early in the course of treatment, and its occurrence was related to dose. The overall mortality in patients treated with sotalol was 4.3% (139 patients); in patients with life-threatening arrhythmias, cardiac mortality was 4.8%. In only 27 patients (0.8%) was the death thought to be potentially drug-related. The deaths were not related to dose. Data from a previously reported placebo-controlled postmyocardial infarction trial indicated no significant difference in mortality between sotalol and placebo. Heart failure was reported in 3.3% of patients and was most prevalent in those with a previous history of congestive heart failure, cardiomyopathy, or structural heart disease. The occurrence of heart failure was unrelated to dose or time on drug; in more than half of the patients, sotalol treatment was continued. On average, there was no decrease in ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346727 TI - Usefulness of sotalol for life-threatening ventricular arrhythmias. AB - Two trial designs have been used in evaluating sotalol in patients with sustained tachyarrhythmias: open-label dose escalation and randomized comparison with reference agents. At least 7 open-label studies (n = 16-65) have been reported from single centers in patients in whom trials of numerous other antiarrhythmic agents were unsuccessful. At the doses used, usually 320-640 mg/day, plasma concentrations were in the range associated with both beta blockade and class III antiarrhythmic activity (2-3 micrograms/mL). These concentrations produced electrophysiologic changes that were consistent across studies: 10-16% increase in right ventricular effective refractory period (ERP), 4-8% increase in corrected QT interval (QTc), and 17-30% increase in sinus cycle length (corresponding to a 15-23% decrease in heart rate). In these open-label trials, sotalol suppressed inducible ventricular tachyarrhythmias in 20-72% of patients; the higher degrees of efficacy were reported when induction protocols were confined to double extrastimuli. Side effects leading to discontinuation of sotalol in patients with sustained ventricular tachycardia or fibrillation include fatigue (4.0%), marked bradycardia (3.0%), torsades de pointes (3.0%), and heart failure or pulmonary edema (1.0%). A multicenter randomized trial compared intravenous sotalol with intravenous procainamide in a double-blind prospective fashion. Sotalol suppressed ventricular tachyarrhythmias inducible with triple extrastimuli in 15 (30%) of 50 patients, whereas procainamide was effective in 10 (20%) of 50. In this and other series, responsiveness to sotalol was prospectively identified by a particularly fast tachycardia at baseline (e.g., cycle length of < 270 msec), but not by the extent of changes in global indices of repolarization (QTc, ERP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346728 TI - Safety and efficacy of oral sotalol for sustained ventricular tachyarrhythmias refractory to other antiarrhythmic agents. AB - The safety and efficacy of oral sotalol were evaluated in 481 patients with drug refractory sustained ventricular tachyarrhythmias (VT) in an open-label multicenter study. After drug-free baseline evaluations, therapy was initiated at 80 mg every 12 hours, with upward dose titrations of 160 mg/day being allowed at intervals of 72 hours to a maximum dose of 480 mg every 12 hours. Efficacy determinations were made by either programmed electrical stimulation (PES) or Holter monitoring responses. Of the 481 patients enrolled, 473 underwent acute phase titration. Of the 269 patients assessable by PES, 94 (34.9%) exhibited complete response (suppression of inducible VT), with an additional 67 patients (24.9%) exhibiting partial response. Of the 109 patients assessable by Holter monitoring, 43 (39.4%) exhibited a complete response. There were no significant differences between responders and nonresponders with regard to left ventricular ejection fraction. Although response rates tended to improve as the sotalol dose was increased to 640 mg/day, efficacy was most commonly achieved at a sotalol dose of 320 mg/day. Sotalol was discontinued because of adverse effects in 42 (8.9%) of the acute-phase patients. The most common adverse effect was proarrhythmia, which was observed in 23 patients (4.9%). Proarrhythmia took the form of torsades de pointes in 12 patients and an increase in VT episodes in 11. In 3 acute-phase patients (0.6%), sotalol was discontinued because of the emergence of congestive heart failure. A total of 286 patients entered the long term phase. Life-table estimates of the proportion of patients who remained free of recurrence of arrhythmia at 12, 18, and 27 months were 0.76, 0.72, and 0.66, respectively. There were no significant differences in time to recurrence of arrhythmia as related to PES response, Holter monitor response, baseline left ventricular ejection fraction, or history of congestive heart failure. Among the 70 patients (24.5%) in whom there was recurrence of arrhythmia, sudden death occurred in 17 and sustained VT in 41. Sotalol was discontinued owing to presumed adverse effects in 21 (7.3%) of the long-term patients, including 8 with proarrhythmia; proarrhythmia consisted of torsades de pointes in 3 patients and increased episodes of VT in 5. These findings suggest that sotalol is an effective drug for the long-term treatment of patients with drug-refractory sustained VT. Proarrhythmia was observed in only 6.4% of the study population and tended to occur during the acute titration phase. The need to discontinue therapy because of congestive heart failure was uncommon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8346729 TI - Effect of sotalol on heart rate variability assessed by Holter monitoring in patients with ventricular arrhythmias. AB - Reduced vagal activity has been demonstrated to be associated with an increased risk of sudden death. Assessing the heart rate variability as a measure of the autonomic control of the heart has been established as a useful tool for the risk stratification of patients after myocardial infarction. In the current study, heart rate variability assessed by time- and frequency-domain measures was determined from Holter recordings before and during treatment with sotalol in 28 patients with chronic ventricular arrhythmias. The heart rate variability at baseline was independent of the presence or absence of spontaneous arrhythmias and of left ventricular function. Therapy with sotalol produced a significant improvement over control values in indices of parasympathetic tone (root mean square of the difference in successive RR intervals, proportion of adjacent RR intervals different by > 50 msec, high-frequency power spectrum). This improvement was not related to drug-induced changes in the mean heart rate or the suppression of ventricular ectopic activity. These effects on heart rate variability may contribute significantly to the overall efficacy profile of sotalol. PMID- 8346730 TI - Effect of sotalol on ventricular fibrillation and defibrillation in humans. AB - Antiarrhythmic drugs are frequently administered to patients receiving implanted cardioverter defibrillators. Some of these drugs may decrease the efficacy of defibrillation shocks from the defibrillator. Sotalol, a drug with beta-blocking and class III antiarrhythmic properties, lowers defibrillation energy requirements in experimental animals and may do so in humans. Oral sotalol 171 +/ 58 mg was administered before and after device implantation in 25 patients receiving implanted defibrillators. During sotalol therapy, the lowest energy required for successful defibrillation was 5.9 +/- 3.4 J (range 2-15J). In a concurrent nonrandomized comparison group of 23 patients, including 18 treated with amiodarone, the lowest successful energy was 16 +/- 10 J (p < 0.01). In 5 sotalol patients, ventricular fibrillation (VF) could not be induced at all (1 patient) or more than 2 or 3 times (4 patients) despite repeated 60 Hz stimulation. The induced VF had a pronounced tendency to terminate spontaneously, with the termination occurring at up to 23 seconds after the offset of 60 Hz stimulation. The cycle length of the VF was 236 +/- 34 msec, significantly greater than in patients not given drug therapy (191 +/- 21 msec, p < 0.01). In 10 patients, but none of the controls, intracardiac electrograms during surface electrocardiographic VF were regular, monoform, and without low-amplitude diastolic activity. In addition, monophasic action potentials during apparent VF showed maintenance of distinct and normal morphology. The ventricular effective refractory period increased after sotalol (249.4 +/- 19 to 278.4 +/- 24 msec; p < 0.03) and the maximum heart rate response to exercise was limited to 120 +/- 28 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346731 TI - Electrophysiologic basis for the antiarrhythmic actions of sotalol and comparison with other agents. AB - Although synthesized as a nonselective beta-adrenergic blocking compound, sotalol has emerged as the prototype of the so-called class III antiarrhythmic compounds. It delays cardiac repolarization by inhibiting the delayed rectifier potassium current, having a lesser effect on the inward rectifying potassium current with little or no effect on the inward calcium or sodium currents. This property of prolonging repolarization with an accompanying increase in the effective refractory period is not due to blockade of the beta-adrenergic receptors. The major electrophysiologic profile of sotalol constitutes the summed effects of beta blockade and prolonged repolarization. Sotalol exerts a potent antifibrillatory action modulated by its antiadrenergic effects. It suppresses premature ventricular contractions and nonsustained ventricular tachycardia while preventing inducible ventricular tachycardia and fibrillation in patients with advanced structural heart disease. The compound is therefore likely to exert a broad spectrum of antiarrhythmic actions in ventricular arrhythmias. PMID- 8346732 TI - Practical considerations in the use of sotalol for ventricular tachycardia and ventricular fibrillation. AB - Sotalol is a unique antiarrhythmic drug that combines beta-blocking effects with actions to prolong action potential duration. The net effect is a drug that is efficacious in the management of ventricular tachyarrhythmias. Although sotalol has effects on both heart rate and QT interval, these effects do not help predict the antiarrhythmic efficacy of the agent. Changes in QT dispersion may, however, prove to be relevant to both the antiarrhythmic effects and the arrhythmogenic effects of sotalol. Thus, although sotalol may occasionally cause torsades de pointes, this complication may be predictable and clinically controllable. Sotalol is well tolerated, and it may be used, with caution, in some patients with impaired myocardial contractile performance, despite its beta-blocking action. Sotalol has an important indication for the management of ventricular tachyarrhythmias. PMID- 8346733 TI - The biology of the clinical pathologist. PMID- 8346735 TI - Something old? Something new? Second primary or pulmonary metastasis in the patient with known extrathoracic carcinoma. PMID- 8346734 TI - Adenocarcinoma in the lung in patients with breast cancer. A prospective analysis of the discriminatory value of immunohistology. AB - In some patients with a history of breast cancer who also have masses in the lung, making a clinical distinction between primary pulmonary neoplasia and pulmonary metastasis of mammary carcinoma may be impossible. To ascertain whether immunohistologic studies could contribute to resolving this problem, the authors undertook a prospective study of 30 cases showing synchronous or metachronous adenocarcinomas in these two sites. A predefined panel of antibodies--as derived from published antigenic catalogs for breast and lung cancer--was applied to each case. Tumors were interpreted as metastases if they were positive for gross cystic disease fluid protein-15, estrogen receptor protein, or S-100 protein. Conversely, primary adenocarcinomas of the lung were defined by their expression of carcinoembryonic antigen and a lack of the other three determinants. Using these criteria, 15 lesions were classified as metastatic; 11 were categorized as primary pulmonary adenocarcinomas; and 4 cases were indeterminate in origin. Responses to corresponding therapeutic protocols generally supported the validity of the immunohistologic diagnoses; 8 of 15 patients treated for metastatic breast cancer were well at least contact, as were 5 of 11 patients who received therapy for primary carcinoma of the lung. These data suggest that immunohistology plays a useful role in distinguishing mammary from pulmonary adenocarcinomas. PMID- 8346736 TI - Emergence of antimicrobial resistance in gram-negative bacilli causing bacteremia during therapy. AB - Treatment of serious infections caused by gram-negative bacilli with beta-lactam antimicrobial agents can induce Class I beta-lactamase production. This phenomenon can result in resistant microorganisms, and has been postulated to be a cause of therapeutic failure. The charts of patients bacteremic with Pseudomonas aeruginosa, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii, Proteus vulgaris, and Providencia species (n = 120) during a 3-year period were reviewed to determine how common the emergence of resistance was, and to determine if in vitro susceptibility testing was a reliable therapeutic guide. Emergence of resistance was believed to occur when a subsequent bacteremic isolate showed at least a fourfold increase in minimum inhibitory concentration accompanied by a change of interpretive susceptibility category. In the group of patients who survived at least 48 hours that received beta-lactam therapy (n = 76), one case of emergence of resistance was identified (1.3%). Emergence of resistance to beta-lactam antimicrobial agents did not commonly cause therapeutic failure at our institution, and susceptibility testing of gram-negative bacilli by usual methods was a reliable guide to antimicrobial therapy. PMID- 8346737 TI - Disseminated bacillus Calmette-Guerin infections in patients with primary immunodeficiencies. AB - The pathologic findings from biopsy or autopsy material in four patients, who were vaccinated with bacillus Calmette-Guerin (BCG) at birth in Chile, are presented. Two patients had severe combined immunodeficiency, and two had more restricted cellular (T-cell) immunodeficiency with no evidence of human immunodeficiency virus infection. The patients had distinct skin nodules and nodular lesions in systemic organs and bone marrow. Three patients had regional BCG lymphadenitis. One patient with severe combined immunodeficiency, however, had disseminated BCG without any local reaction. In all cases BCG strains of Mycobacterium were identified in a reference mycobacteriology laboratory. The histologic lesions in most patients usually consisted of diffuse histiocytic infiltrates with poorly formed granulomas and variable or no necrosis. Histiocytes were plump and engorged with numerous acid-fast bacilli (AFB). In some areas the massive histiocytosis resembled a spindle cell neoplasm. Other histologic findings supported the underlying immunodeficiency. The pattern of histiocytic response and degree of microbial killing depend on the host's immunocompetence. In the later stages of disease or in severe immunodeficiency, there is a lack of granuloma formation and unimpeded proliferation of AFB. These findings are reminiscent of nontuberculous mycobacterial infections in AIDS patients. Bacillus Calmette-Guerin dissemination has to be considered in immunocompromised individuals when the patient comes from other countries in which such vaccinations are practiced. PMID- 8346738 TI - Marrow B-cell precursors are increased in lymphomas or systemic diseases associated with B-cell dysfunction. AB - Marrow regeneration is known to be associated with an increase in immature B cells, including CD10+ cells. A similar phenotype has been seen in some children with unusual cytopenias. This article describes 21 adult patients not recovering from chemotherapy, who had increased CD10+ cells in their marrows. These cells had the relatively uniform scatter properties of small lymphocytes by flow cytometry, and by multiparameter analysis were found to have a distinct phenotype in that they were CD19+, lacked surface immunoglobulin, and heterogeneity expressed CD20. In two of three patients tested, some but not all of these early B cells were TdT+. CD10+ cells accounted for 10-76% of total mononuclear cells. All 21 patients had some systemic illness. Thirteen patients had a diagnosis of lymphoma (three Hodgkin's, ten non-Hodgkin's); all ten of the latter were extranodal and seven of seven phenotyped cases were B-cell lymphomas. Seven patients had autoimmune disease (one also had lymphoma) and one had the acquired immunodeficiency syndrome with mycobacterial infection of the marrow. One patient with a history of a "viral illness" had a lymph node showing atypical lymphoid hyperplasia with progressive transformation of germinal centers. Examination of marrow core biopsies in these patients showed a proliferation of small lymphocytes ranging from a barely perceptible diffuse increase to numerous lymphoid aggregates. The extensive lymphocytosis seen in two marrows suggested a diagnosis of lymphoma on morphologic grounds alone, but neither these patients nor any others had B-cell clonal excess. The presence of this phenotype suggests nonspecific stimulation of marrow B-cell precursors associated with systemic B cell activation in either an immunologic or neoplastic disorder. Presence of this unusual phenotype does not imply involvement of marrow by B-cell neoplasia. PMID- 8346739 TI - Informatics. A subspecialty in pathology. AB - The emerging discipline of pathology informatics is reviewed, and its placement as a subspecialty within the broader field of pathology and laboratory medicine is proposed. Informatics concepts should guide the development of the next generation of laboratory information systems. Advanced laboratory systems will incorporate decision support leading to improvements in quality and in interpretive reporting providing support for clinical diagnosis and decision making. Training programs in pathology should take into account the need for expertise in informatics and develop fellowships in this area to adequately prepare junior faculty members for their future professional role. PMID- 8346740 TI - Limitations of the osmolal gap with toxin ingestion. PMID- 8346741 TI - Undertransfusion. PMID- 8346742 TI - Correction. PMID- 8346743 TI - Anabolic steroids--round 4. PMID- 8346744 TI - Effect of surgical timing on recovery and associated injuries after anterior cruciate ligament reconstruction. AB - This study was undertaken to determine the optimal time after injury for arthroscopically assisted anterior cruciate ligament reconstruction using a double semitendinosus graft. We analyzed 87 patients. Time from injury to surgery was established as acute, subacute, or chronic; the three groups were matched. Meniscal damage and treatment were categorized. Chondral lesions were graded, postoperative parameters of motion, strength recovery, and stability were tabulated at 3, 6, 12, and 18 months. Complications were compared. Six percent of the patients with chronic knee injuries had two normal menisci at surgery, compared with 29% of the acute and subacute groups. Reparable tears were found in 37.8% of the knees. Chondral lesions were found in the tibiofemoral joint in 17% of acute, 7% of subacute, and 44% of the chronic knees. Postoperative motion recovery was significantly less at all time intervals for the acute group. Quadriceps strength recovery was slower in the acute knees. Stability was similar in all groups. Arthrofibrosis was found in 22% of acute, 0 subacute, and 12.5% of the chronic knees. Patellofemoral pain was noted in 17% of the acute, 0 of the subacute, and 9.3% of the chronic knees. This study showed that surgery done within 6 months of injury does not jeopardize the knee. Recovery after acute anterior cruciate ligament reconstruction is significantly slower than after subacute or chronic reconstruction. PMID- 8346745 TI - Arthrography for the diagnosis of acute lateral ligament injuries of the ankle. AB - Arthrography was used for diagnosis of ruptures of lateral ligaments in 589 acutely injured ankles that were treated operatively. The accuracy of the method was tested comparing the findings of arthrography with those at operation. We found arthrography to be almost 100% reliable for diagnosing a fresh anterior talofibular ligament rupture. The best criterion for detecting calcaneofibular ligament rupture was filling of the peroneal tendon sheath with contrast medium. Leakage below and behind the lateral malleolus, when present with peroneal tendon sheath filling, confirms the diagnosis of calcaneofibular ligament rupture, but these findings without peroneal tendon sheath filling are too rare to base the diagnosis on them alone. PMID- 8346746 TI - Arthroscopic Bankart suture repair. AB - The purpose of this paper was to report our experience with an arthroscopic technique of repair for the Bankart lesion following shoulder instability. Twenty seven patients (average age, 21.7 years) were followed for an average of 36 months after arthroscopic suture stabilization of anterior shoulder instability. Patients were excluded if instability was multidirectional or voluntary and if there was radiographic evidence of a significant loss of glenoid bone stock. Clinical evaluation using a functional grading system showed that 10 patients were rated as excellent, 5 good, and 12 poor. Fourteen patients returned to their previous level of activity. There were 12 patients rated as failed; all had recurrent instability of the shoulder. Success was associated with a period of immobilization of 3 weeks or longer and a history of acute injury, especially subluxation. Failures were associated with shorter immobilization periods after surgery and in patients who had recurrent dislocations. The younger patient, who may not have complied with the immobilization protocol, also seemed to be associated with failure. Contact sports seems to leave a patient at high risk for recurrence. We recommend caution in the use of arthroscopic procedures for the competitive athlete in whom a second surgery and rehabilitation might mean loss of more sports participation. PMID- 8346747 TI - Longitudinal rupture of the peroneal tendons. AB - To determine more precisely the injury mechanism of the peroneal tendon longitudinal tear, we studied 15 cadaveric lower extremities. Our study was motivated by our observation from a retrospective study of athletes treated by one surgeon (FHB) over a 17-year period. Eight patients who sustained lateral ankle sprains by plantar flexion and inversion of the foot on the leg also had longitudinal tears (1 to 3 cm) of the peroneal tendon--five in the peroneus longus and three in the peroneus brevis. All of the lateral ankle sprains were successfully managed nonoperatively. However, even after a period of rehabilitation, when their ankles should have been asymptomatic, the patients continued to complain of persistent lateral ankle swelling, popping, and retrofibular pain. On physical examination, all ankles were clinically stable. Palpable retrofibular popping occurred with active foot rotation. There was no evidence of peroneal tendon instability. Radiographs were normal and tenograms were suggestive of peroneal tendon injury but did not have the specificity to reveal the rupture. Primary suture repair of this peroneal tendon split was performed and gave excellent long-term results. The cadaveric studies revealed that the tear of the tendon could occur in the 25 degrees to 15 degrees range of plantar flexion as the peroneus longus impinged against the tip of the fibula and as the peroneus brevis impinged against the lateral wall of the peroneal groove or against the longus tendon. PMID- 8346748 TI - Reconstruction of old anterior cruciate ligament tears with a Dacron prosthesis. A prospective study. AB - Seventy patients with chronic anterior instability underwent anterior cruciate ligament reconstruction with a Dacron prosthesis pretensioned to 60 N. Of these patients, 49% (34%) had combined medial instability, 32% (22) had failed previous anterior cruciate ligament surgery, and 37% (26) had previous meniscectomy. At reconstruction, 12 patients had their medial instability treated; 22 did not. Follow-up intervals were 3, 6, and 12 months and then each year to 5 years. The 5 year followup included 69 patients; the other 1 had the ligament removed because of a synovial fistula at 8 months. Results were 23% prosthesis ruptures, 3% poor, 17% fair, 16% good, and 39% excellent. The 2-year results showed the same distribution, but a lower rupture rate, which was affected by placement of the tibial tunnel within the anterior one-third of the tibia (9 times increase) and coexisting nonrepaired medial instability (5 times increase). Those patients with perfect placement of the ligament who also had good medial stability and no previous ligament surgery had no rupture at 5 years. The stability that was gained at surgery was gradually lost (-11.2% per year). At 5 years, the uninjured knee also had lost 41% of the preoperative stability; the mean laxity difference was within +/- 2 mm. The mean improvement in subjective knee function (Lysholm score 74.5 to 91.9) was maintained during the followup. The mean preoperative activity level improved significantly, but did not reach the preinjury level. These results show that the Dacron prosthesis will not give acceptable results in salvage cases where other instabilities are left untreated. PMID- 8346749 TI - The Dacron ligament prosthesis in anterior cruciate ligament reconstruction. A four-year review. AB - We studied 40 patients who underwent reconstruction for chronic anterior cruciate ligament deficiency with a Dacron ligament prosthesis using a modified MacIntosh over-the-top technique, augmented with iliotibial band. Thirty patients had undergone at least 1 prior surgical procedure on the affected knee, but only 7 patients had previous anterior cruciate ligament reconstruction. All patients were followed for a mean of 47.5 months. The results at final followup demonstrated an average side-to-side arthrometer difference of 1.0 mm. The Lysholm score improved from 65 preoperatively to 89 at the end of the review; the Tegner activity level score improved from 3 to 5. Objectively, 75% of the patients had a negative Lachman test result and 95.1% of the subjects had negative or trace pivot shift results at review. Mild knee pain was still present with day-to-day activity in 87.7% of the patients. Complications occurred in 27.5% of patients, including five who had implant ruptures and two who had their grafts removed. Synovitis was a significant problem. Based on our failure criteria, 47.5% (19) of the subjects had failed results. In this study, radiologic evidence of tracer separation greater than 1 cm was a criterion of failure. With inclusion of tracer separation, the failure rate increased to 60.0% (24). Multiple previous surgeries of any type had an adverse effect on results. Damage to secondary stabilizers in these cases increased failure rate. Based on the high complication and failure rates, and relatively poor end result in this retrospective review, we cannot recommend this procedure. PMID- 8346750 TI - Dacron ligament reconstruction for chronic anterior cruciate ligament insufficiency. AB - We report the 5-year follow-up results of a prospective, multicenter study evaluating the use of a Dacron prosthetic ligament in reconstruction of anterior cruciate-deficient knees. The study group consisted of 84 patients, followed for at least 5 years. The patients were divided into 2 groups: 50 patients with isolated anterior cruciate ligament laxity (Group 1) and 34 patients with a failed previous anterior cruciate ligament surgery or combined laxities (Group 2). Two surgical techniques were employed: reconstruction through drill holes in the tibia and femur (30 patients) and reconstruction using the over-the-top position with the Dacron ligament wrapped in a strip of iliotibial band (54 patients). The overall failure rate was 35.7% at 5 years. The failure rate at 2 years was 20%, illustrating a significant deterioration of results between the two follow-up intervals. Evaluation of subjective criteria using the Lysholm score showed an improvement from preoperative status at the 2-year followup; however, there was a slight decline when 5-year results were evaluated. Tegner activity levels increased from a mean of 2.9 +/- 2.1 at the preoperative visit, to a mean of 4.9 +/- 2.0 at the 2-year followup and a mean of 5.0 +/- 2.0 at the 5-year visit. These results show that the Dacron ligament prosthesis achieves the short-term goal of restoring stability and improving function and may be sufficient to provide long-term stability for the anterior cruciate-deficient knee. PMID- 8346751 TI - Surgical treatment of Freiberg's infraction in athletes. AB - Ten patients with 11 cases of Freiberg's infraction were studied retrospectively. The patients had varying amounts of sports participation. All cases were treated surgically, most after some form of nonoperative intervention. Surgery consisted of metatarsophalangeal joint debridement, except in 1 patient where the metatarsal head was resected. All patients had improvement of their symptoms and 80% of normal joint range of motion was restored. No patient had joint space narrowing or major arthritic changes on follow-up roentgenographic studies. PMID- 8346752 TI - Electromyographic analysis of the trunk in golfers. AB - Golf is a popular sport for both men and women. The trunk is the most common area of injury during the golf swing. The purpose of this study was to describe and compare the muscle firing patterns in the trunk during the golf swing. Twenty three golfers with handicaps of five or below volunteered for this study. Surface electromyographic electrodes were placed on the abdominal oblique and erector spinae muscles bilaterally. High-speed cinematography was used in conjunction with the electromyographic electrodes. The results demonstrated relatively low activity in all muscles during takeaway (below 30% of maximal muscle test), and relatively high and constant activity throughout the rest of the swing (above 30% maximal muscle test, with the exception of the contralateral erector spinae during late follow-through, which was 28% maximal muscle test). This high and constant activity demonstrated the importance of the trunk muscles during a golf swing. These results indicate the need for an effective preventive and rehabilitative exercise program for the golfer. PMID- 8346753 TI - Comparison of symptomatic versus nonsymptomatic patients with chronic anterior cruciate ligament insufficiency. Radiographic sagittal displacement during weightbearing. AB - The sagittal anterior displacement of the tibia, induced by weightbearing, in chronic anterior cruciate ligament-insufficient knees was measured radiographically in 2 groups of patients. All patients in both groups had an increased laxity when assessed with the Lachman and flexion-rotation-drawer test. Sixteen patients were functionally improved and were relatively asymptomatic after a neuromuscular rehabilitation program, while the second group consisted of another 16 patients with persistent functional instability, despite the same rehabilitation program, who eventually had ligament reconstruction. The mean radiographic anterior displacement during weightbearing in the nonsymptomatic group was 4.3 mm, and 8 patients had a displacement < or = 2 mm. In the symptomatic group, the corresponding value was 8.1 mm (P < 0.05), and 3 patients had a displacement < or = 2 mm. No correlations to meniscal injuries, age, or time from injury were found between the patients having a displacement >2 mm and those with < or = 2 mm. The findings should be explained by differences in neuromuscular control of the increased laxity in the injured knee. PMID- 8346754 TI - Electromyographic and cinematographic analysis of elbow function in tennis players using single- and double-handed backhand strokes. AB - It is generally believed that tennis players using a double-handed backhand rarely develop lateral epicondylitis since the helping arm appears to absorb more energy and changes the mechanics of the swing. The purpose of this paper was to compare muscle activity about the elbow in single- and double-handed backhand strokes in competitive tennis players. Muscle activity in 3 elbow extensors, a wrist flexor, and a forearm pronator of the dominant arm was compared during the single-handed (N = 14) and double-handed (N = 13) backhand ground strokes using indwelling electromyography and high-speed cinematography. Significantly higher activity was seen in the double-handed technique in the flexor carpi radialis muscle in the preparation phase and in the pronator teres muscle in the acceleration phase. Higher flexor carpi radialis muscle activity in preparation of the double-handed stroke appeared to be a function of the double-handed grip used on the racquet, and the increased pronator teres muscle activity in acceleration indicated maintenance of greater pronation provided by the grip of the non-dominant hand. The decreased occurrence of lateral epicondylitis in players using a double-handed backhand may not be caused by decreased extensor activity, but rather by factors associated with flawed stroke mechanics more often seen in the single-handed technique. PMID- 8346755 TI - Biceps tendon tenodesis for posterolateral instability of the knee. An in vitro study. AB - The effects of biceps tendon tenodesis on internal-external and varus-valgus laxity were measured using fresh-frozen cadaveric specimens that had undergone sequential sectioning of the posterolateral structures and of the fibular collateral ligament. Tenodesis (using 89 N graft tension and a fixation point located 1 cm anterior to the fibular collateral ligament's insertion on the femur) was effective in restoring external rotation and varus laxity; the procedure actually overconstrained external tibial rotation at all flexion positions and varus angulation at 60 degrees and 90 degrees of flexion. Internal rotation and valgus laxity were unaffected by the tenodesis procedure. The anterior fixation point was more effective in reducing laxity than a fixation point located 1 cm proximal to the fibular collateral ligament insertion. Tenodesis using the proximal fixation point, which was nonisometric, did not restore external rotation and varus laxities to intact values at 60 degrees and 90 degrees of knee flexion. Graft tension (45 or 89 N) had no measurable effect on the results of the tenodesis. This study has demonstrated that the biceps tenodesis procedure is effective for reducing static laxity in the knee with posterolateral instability. PMID- 8346756 TI - Posterior subluxations of the medial and lateral tibiofemoral compartments. An in vitro ligament sectioning study in cadaveric knees. AB - We report for the first time the abnormal increases in posterior subluxation of the medial and lateral tibial plateaus after sectioning the posterolateral structures and posterior cruciate ligament. We applied specific forces and moments to the knees of seven cadaveric whole lower limbs and measured the position of the tibia at which the ligaments and the geometry of the joint limited motion. Removal of only the posterolateral structures resulted in an average increase in posterior translation of the lateral tibial plateau of 8.0 mm (range, 5.7 to 10.6) at 30 degrees of flexion over the intact state (P < 0.01), but no significant increase at 90 degrees of flexion (mean, 2.7 mm). Knees with underlying physiologic cruciate ligament laxity (high anterior/posterior displacement in the intact knee) had the greatest lateral tibial plateau subluxation (P < 0.01). There was no abnormal posterior translation of the medial tibial plateau. After sectioning the posterior cruciate ligament and the posterolateral structures, statistically significant increases in posterior translation of both the medial and lateral tibial plateaus occurred at 30 degrees and 90 degrees of flexion (P < 0.01). The increase in posterior translation of the lateral tibial plateau over the intact state averaged 17.8 and 23.5 mm at 30 degrees and 90 degrees of flexion, respectively; for the medial tibial plateau this increase averaged 7.6 and 12.3 mm at 30 degrees and 90 degrees of flexion, respectively. The diagnosis of abnormal tibiofemoral rotatory subluxations requires knowledge of the anteroposterior direction and magnitude of each tibial plateau under both low flexion and high flexion knee angle positions. PMID- 8346757 TI - Anterior cruciate ligament reconstruction. The effect of tibial tunnel placement on range of motion. AB - In 111 patients who had anterior cruciate ligament reconstructions, postoperative radiographic measurements of anterior to posterior and medial to lateral location of the tibial tunnels were correlated with the final range of motion achieved. In the 25 patients with extension deficits of 10 degrees or more, placement of the tibial tunnel was more anterior (average, anterior 23% of the tibia) than in the remaining 86 patients with extension deficits of < 10 degrees (average, anterior 29% of tibia). This difference was statistically significant with P < 0.001. Logistic regression analysis revealed that the more anterior the placement of the tibial tunnel, the greater the loss of both flexion (P = 0.01) and extension (P = 0.002). In the 21 patients with full extension but flexion < 130 degrees, placement of the tibial tunnel tended to be more medial (average, medial 40% of the tibia) than in the 65 patients without flexion deficit (average, medial 45% of the tibia). We conclude that placement of the tibial tunnel in the "eccentric," anteromedial position may contribute to the development of flexion and extension deficits after anterior cruciate ligament reconstruction. PMID- 8346758 TI - Arthroscopic treatment of glenoid labral tears. AB - We reviewed 52 consecutive patients who had undergone arthroscopic labral debridement. The average age was 29 and there were 35 men and 17 women. At operation, 27 patients had superior labrum anterior and posterior (SLAP) lesions, 20 patients had anteroinferior labral lesions, and 5 patients had posterior labral lesions. Despite the fact that, preoperatively, none of these patients had a history of dislocations or clinically evident instability, 70% of the patients with superior labral lesions, and all of those with anteroinferior and posterior lesions had instability on examination under anesthesia. The average followup was 36 months. At 1 year after arthroscopy, 78% of the patients with superior lesions had excellent relief compared with 30% of the patients in the anteroinferior group. At 2 years followup, these results decreased to 63% and 25%, respectively, and only 45% of the patients with superior labral lesions and 25% of those with anteroinferior lesions had returned to their previous athletic performance level. Four patients required a reoperation: 2 for instability and 2 for impingement. We conclude that occult instability is frequently present in patients with glenoid labral tears. The overall results are not encouraging, but this procedure may have an indication for short-term goals in competitive athletes or those who are willing to accept some compromise in function. PMID- 8346760 TI - Biomechanical considerations in patellofemoral joint rehabilitation. AB - Patellofemoral joint biomechanics during leg press and leg extension exercises were compared in 20 normal subjects (10 men, 10 women) aged 18 to 45 years. Knee moment, patellofemoral joint reaction force, and patellofemoral joint stress were calculated for each subject at four knee flexion angles (0 degree, 30 degrees, 60 degrees, and 90 degrees) during leg press and leg extension exercises. All three parameters (knee moment, patellofemoral joint reaction force, and patellofemoral joint stress) were significantly greater in leg extension exercise than leg press exercise at 0 degree and 30 degrees of knee flexion (P < 0.001). At 60 degrees and 90 degrees of knee flexion, all three parameters were significantly greater in leg press exercise than leg extension exercise (P < 0.001). Patellofemoral joint stresses for leg press and leg extension exercises intersected at 48 degrees of knee flexion. This study demonstrates that patients with patellofemoral joint arthritis may tolerate rehabilitation with leg press exercise better than with leg extension exercise in functional ranges of motion because of lower patellofemoral joint stresses. PMID- 8346759 TI - Isolated arthroscopic partial meniscectomy. Functional radiographic evaluation at five years. AB - Fifty patients who underwent isolated arthroscopic partial meniscectomy with a minimum followup of 5 years were analyzed retrospectively. To analyze the factors associated with a satisfactory or an unsatisfactory clinical result, we looked at the patient's age, duration of symptoms, type of meniscal lesion, and articular cartilage abnormalities. The patients were graded with a functional knee score (Lysholm-Gillquist), and activity level before surgery and at followup was determined. The data also included radiographic evaluation of 29 of the 50 patients. Tibiofemoral alignment was measured, and osteoarthritic changes were graded and correlated with the type of meniscal abnormality and functional result. Eighty-two percent of our patients had satisfactory knee function, and the activity level was maintained. The factors associated with a satisfactory result after a partial meniscectomy included age less than 40 years, symptoms less than 12 months duration, type of tear, and chondromalacia less than grade II. Fairbank's changes were present in 50% of the patients, with significant grade III and IV changes identified in 30%. Although the radiographic changes did not necessarily correlate with the functional result, we felt that the changes were significant and indicative of abnormal stress transfer to articular cartilage and bone. PMID- 8346762 TI - Patellar tendon length change after anterior cruciate ligament reconstruction using the midthird patellar tendon. AB - The purpose of this study was to determine if use of the midthird patellar tendon autograft contributes to or causes patellar tendon shortening or patella baja in anterior cruciate ligament reconstruction. Thirty-six patients undergoing arthroscopically assisted midthird patellar tendon autograft anterior cruciate ligament reconstruction were studied prospectively. Intraoperative patellar tendon length changes were measured. Half of the patients had the tendon defect closed and half had it left open (closing peritenon only). Radiographic tendon length changes and patella baja were assessed using Insall-Salvati and Blackburne Peel ratios measured on 45 degrees lateral knee radiographs using an adjustable polypropylene jig. Bilateral films were obtained preoperatively and at 2 weeks, 3 months, and 6 months postoperatively. No patients demonstrated evidence of patellar tendon shortening greater than the 5.5% measurement error. Tendon defect closure resulted in negligible tendon shortening intraoperatively, averaging 2.28% (1.11 mm). Of the 18 patients whose defects were closed, 5 showed no shortening. The remaining 13 patients had measurable tendon shortening less than 4% (2 mm). No patients developed patella baja. PMID- 8346763 TI - Partial meniscectomy and anterior cruciate ligament rupture in soccer players. A study with a minimum 20-year followup. AB - A retrospective review of 77 soccer players with 91 affected knees that had undergone the same operation, a rim-preserving meniscectomy, was made with a minimum followup of 20 years and an average followup of 27 years. The patients were divided into groups based on the presence of an intact (Group 1) or ruptured (Group 2) anterior cruciate ligament. At 5 years after meniscectomy, 75% of Group 1 and 52% of Group 2 were still playing soccer, and 13% in Group 1 as opposed to 28% in Group 2 had given up sports. The sporting class assessment was good in 80% of the Group 1 knees and 62% in the Group 2 knees. By followup, 5% of Group 1 and 32% of Group 2 required further meniscectomies, and 2% of Group 1 and 16% of Group 2 required operations for osteoarthritis. Radiologically diagnosed osteoarthritis was present in 24% of Group 1 knees compared with 77% of Group 2. Functionally, 60% of the Group 1 knees were excellent at followup as opposed to 9% in Group 2 knees. In Group 1, 49% were still involved in sports compared with 22% in Group 2. However, 97% of Group 1 were satisfied with their knees compared with 74% of Group 2. All of these differences were statistically significant. PMID- 8346761 TI - Development of lower leg strength and flexibility with the strength shoe. AB - The Strength Shoe is a modified athletic shoe with a 4-cm thick rubber platform attached to the front half of the sole. It is promoted as an effective method of increasing "speed, quickness, and explosive power," as well as ankle flexibility and calf circumference, when used in a plyometrics-based training regimen. This study evaluates, in a prospective, randomized trial, the efficacy and safety of the Strength Shoe training regimen for increasing lower leg flexibility and strength in intercollegiate track and field participants. No enhancement of flexibility, strength, or performance was observed for participants wearing the Strength Shoe at the end of an 8-week training program, following the suggested regimen of the manufacturer. The use of the Strength Shoe cannot be recommended as a safe, effective training method for development of lower leg strength and flexibility. However, the use of plyometrics in a properly supervised setting may improve athletic performance and merits further investigation. PMID- 8346764 TI - Injuries in recreational adult fitness activities. AB - Volunteers (986) from fitness clubs and studios were recruited and followed for a 3-month period to document the injury consequences of adult recreational fitness participation. Participants were telephoned each week and their activities as well as any injuries that occurred were recorded. Of the 525 injuries and complaints reported during 60,629 hours of activity, 475 occurred as a result of sports participation for an overall rate of 7.83 per 1000 hours of participation. Seventy-six percent of these episodes caused the patient to alter or miss 1 or more activities, while 9.5% involved a physician visit. The rate for time-loss injuries was less than 2 per person per year (1.76 per 298 hours) or 5.92 per 1000 hours. Running had a higher risk of injury compared with most other individual sports. Cardiovascular fitness activities had low to medium rates, as did weight work; competitive sports were higher. For 6 of the most commonly injured areas, the reinjury rate was about twice that reported for those with no history of previous injury. The risks of injury from most recreational fitness activities were relatively modest, particularly if the activities were not competitive. Physicians might help patients reduce their risks of injury by encouraging suitable activities and by reducing the risks of reinjury by implementing appropriate rehabilitation programs. PMID- 8346765 TI - Anabolic steroids and growth hormone. AB - Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation. PMID- 8346766 TI - Rupture of the pectoralis major muscle in a collegiate football player. Use of magnetic resonance imaging in early diagnosis. AB - We have reported an unusual case of pectoralis major muscle rupture and repair. There were three interesting aspects of this case. First, the injury occurred in a football player with an unusual mechanism of injury. Second, MRI using special techniques was valuable in confirming the diagnosis acutely and in planning treatment. Finally, we reported on the use of suture anchors to secure the avulsed tendon. We recommend the early use of MRI for diagnosis and in planning treatment of suspected pectoralis major muscle ruptures. PMID- 8346767 TI - Nonunion of a medial malleolus stress fracture. A case report. PMID- 8346768 TI - Rupture of the triceps tendon associated with steroid injections. AB - Rupture of the triceps mechanism is an uncommon injury that has been recognized with increasing frequency in recent years. It has been proposed that such injuries commonly accompany fractures of the radial head and must be actively evaluated in the presence of such a fracture. We present a unique case of isolated rupture of the triceps tendon in an athlete who was lifting weights. This case was complicated by a history of olecranon bursitis that had been treated with numerous local steroid injections, as well as a history of anabolic steroid abuse. Both systemic steroids and local injections may predispose tendons to rupture. Triceps tendon ruptures may result in uniformly good to excellent results if recognized and treated surgically. This case also serves as a reminder of the risks of treating inflamed tissues with local steroid injections, especially in strength athletes who place high demands on their musculoskeletal structures. Finally, this case documents a second case of triceps mechanism rupture in an athlete who has abused anabolic steroids. A study by Hunter et al. suggests that oral steroid abuse may be associated with detrimental effects on the mechanical properties of connective tissue, demonstrating another negative effect of anabolic steroid use in athletes. PMID- 8346769 TI - An evaluation of anaesthetic loss from a closed breathing system. AB - We present the results of a laboratory study of the loss of isoflurane from a to and-fro system, ventilated with oxygen, using a standard ventilator connected to the system via a long corrugated tube (the trunk) in place of the reservoir bag. No conventional fresh gas supply is used and isoflurane is injected as a liquid directly into the soda lime canister. The loss of isoflurane from the system due to mixing in the trunk was generally less than that lost by absorption into rubber and plastic system components. Glass syringes used for injection of liquid isoflurane were found to be a potential source of much greater leaks. The results showed that a to-and-fro system ventilated with oxygen via an open trunk functions as a virtually completely closed anaesthetic breathing system. PMID- 8346770 TI - The nasopharyngeal airway. Assessment of position by fibreoptic laryngoscopy. AB - Artificial nasopharyngeal airway position and performance were assessed in 120 anaesthetised adult patients. Using a fibreoptic laryngoscope mean distances from nares to larynx were measured at 209 mm (SD 11) in males and 180 mm (SD 11) in females; those from nares to epiglottis were 159 mm (SD 12) in males and 140 mm (SD 11) in females. Nasopharyngeal airways were frequently misplaced, 60% lying beyond the tip of the epiglottis and 13% lodged in the vallecula. Forty-two percent of subjects had clinical evidence of respiratory obstruction. Nasopharyngeal airway compression in the nasopharynx and obstruction by the tongue and soft palate were common causes of respiratory obstruction. Regression analysis revealed that nares-epiglottis length correlated significantly with subject height (t = 3.9, p = 0.0002), but not with three external measurements made around the head and neck. Head flexion and extension resulted in comparatively little relative movement of the nasopharyngeal airway. Nasopharyngeal airway length and diameter should be standardised to optimise performance. PMID- 8346771 TI - Anxiety levels following anaesthesia for day-case surgery. A comparison of state anxiety levels following induction of anaesthesia with propofol or thiopentone. AB - The effect of different induction agents on postoperative state anxiety levels was investigated. Propofol produces statistically significant lower levels when compared with thiopentone. This finding suggests that propofol should remain the drug of choice for short duration anaesthesia. PMID- 8346772 TI - A comparison of diclofenac and ketorolac for postoperative analgesia following day-case arthroscopy of the knee joint. AB - Seventy-one patients presenting for day-case arthroscopy were randomly allocated to receive either intramuscular diclofenac 75 mg or ketorolac 30 mg immediately after induction of anaesthesia. One hour after operation visual analogue pain scores were significantly lower in the ketorolac group compared with those receiving diclofenac. Pain scores at 2 and 4 h postoperatively were not significantly different between the two groups although six of those receiving diclofenac required opioid analgesia compared with only one in the ketorolac group. Discomfort in the operated knee was similar for both groups on the day following surgery, but pain from the intramuscular injection site was significantly greater in the diclofenac group. Intramuscular ketorolac 30 mg provided better postoperative analgesia and less pain at the injection site than diclofenac 75 mg. PMID- 8346773 TI - The use of propofol in a child with hepatitis A. AB - Propofol was used for the induction and maintenance of anaesthesia in a 4-year old girl with hepatitis A and haematemesis. The anaesthetic was uneventful with no postoperative sequelae. PMID- 8346774 TI - The management of anaesthesia for caesarean section in a patient with paroxysmal ventricular tachycardia. AB - We describe the successful management of general anaesthesia for Caesarean section in a patient with poorly controlled paroxysmal ventricular tachycardia of pregnancy. The use of alfentanil before laryngoscopy and tracheal extubation ensured cardiostability without compromising maternal or fetal wellbeing. General anaesthesia allows prompt cardioversion. We believe that in the presence of a life-threatening unstable cardiac rhythm this consideration outweighs any theoretical advantage of regional blockade. PMID- 8346776 TI - The additional work of breathing imposed by Mapleson A systems. AB - The additional work attributable to breathing through five Mapleson A anaesthetic breathing systems (Magill, Lack, Parallel Lack, Humphrey ADE and Enclosed Magill) was studied using a lung model. With all five systems, the additional work was found to be a function of fresh gas flow, respiratory flow as well as system geometry. Within the range of fresh gas flow and respiratory flow studied, the additional work ranged between 80 mJ.l-1 and 182 mJ.l-1. Expiratory work was always greater than the inspiratory workload. Increasing fresh gas inflow into the system increases expiratory work, both resistive and elastic components. The Magill system posed the least work expenditure. The values for the additional work obtained with the lung model were of the same order of magnitude when measurements were taken in volunteers. PMID- 8346775 TI - Combined high frequency ventilation in the management of respiratory failure in late pregnancy. AB - We describe a pregnant patient with respiratory failure due to an atypical pneumonia and asthma that was successfully treated with the combination of high frequency oscillatory ventilation and intermittent positive pressure ventilation. This combined high frequency ventilatory technique is not commonly used in adults with respiratory failure and is largely contraindicated in patients with prolonged respiratory time constants such as occurs in asthma because of the risk of gas trapping. We suggest that this technique be considered in cases of respiratory failure refractory to conventional intermittent positive pressure ventilation and, that with appropriate monitoring of airways pressure, is worthy of a trial in patients with prolonged respiratory time constants. PMID- 8346777 TI - The genius infrared tympanic thermometer. An evaluation for clinical use. AB - A clinical tympanic thermometer was evaluated. In vitro it was found to be accurate over the temperature range 28 degrees C to 40 degrees C. Clinical assessment was made during the cooling and rewarming phases of patients undergoing surgery with the aid of cardiopulmonary bypass and compared with the results obtained with an Ellab thermocouple thermometer. It was also used in patients in the intensive care unit in whom core temperature was being measured using the thermistor incorporated in a pulmonary artery catheter. The infrared thermometer was found to be accurate, rapidly responding and easy to use. PMID- 8346778 TI - Noninvasive monitoring of respiratory volume. Experimental evaluation of a breath monitoring device. AB - The authors studied the accuracy of the noninvasive breath monitor (Voltek Enterprise, Willowdale, Ontario, Canada) in predicting the tidal volumes in five healthy human volunteers. The signals of the breath monitor were compared with the volumes estimated by a calibrated pneumotachograph. The results show that the breath monitor is considerably accurate and can be accepted as a reliable device for clinical applications. PMID- 8346779 TI - The Finapres 2300e finger cuff. The influence of cuff application on the accuracy of blood pressure measurement. AB - Blood pressure measurements associated with malapplication of a finger cuff were compared with contemporaneous intra-arterial pressure data in seven volunteers to determine the influence of cuff application on the accuracy of the Finapres 2300e. Systolic readings in all cuff positions differed from arterial line data by more than the recommended standard and tight and loose cuff applications under and over-read respectively, in all subjects. The results show the Finapres to be sensitive to small degrees of finger cuff malapplication which contribute to the bias on direct arterial comparison and limit the reliability of the instrument in clinical practice. PMID- 8346780 TI - Breast feeding and anaesthesia. AB - Anaesthetists require a good knowledge of the excretion of drugs in breast milk and the potential hazards to suckling infants of drug ingestion via breast milk. A brief account of the physiology of lactation is given. The mechanisms of drug passage into breast milk are discussed followed by a review of the excretion in breast milk of drugs used in anaesthetic practice. Suggestions for the management of anaesthesia in breast feeding mothers are offered. PMID- 8346781 TI - Myalgia and biochemical changes following suxamethonium after induction of anaesthesia with thiopentone or propofol. AB - The incidence and severity of muscle pains and changes in creatine kinase were assessed following administration of 1 mg.kg-1 suxamethonium either immediately or 2 min after induction of anaesthesia with propofol or thiopentone in patients undergoing elective dental and ophthalmic surgery. The incidence of muscle pains was 35 and 60% respectively in the groups given suxamethonium immediately and 2 min after propofol, and 35 and 55% when given immediately and 2 min after thiopentone, with no statistically significant differences among the groups. Creatine kinase levels increased in all the groups after operation with the least average increase in the group receiving suxamethonium immediately after propofol and the highest increase in the group receiving suxamethonium 2 min after thiopentone. There was no correlation between the incidence and severity of fasciculations, muscle pains and changes in creatine kinase within or between the groups. It is concluded that neither the induction agent nor the time between the induction agent and suxamethonium administration has any significant influence on the incidence of muscle pains or creatine kinase elevation following suxamethonium. PMID- 8346783 TI - More problems with the Selectatec system. PMID- 8346782 TI - Does a bloody tap prevent postdural puncture headache? AB - The regional anaesthesia records of 274 obstetric patients who had inadvertent dural puncture were reviewed to see whether a bloody dural tap resulted in a lower incidence of postdural puncture headache. No such influence was found. PMID- 8346784 TI - Stylet for reinforced laryngeal mask airway. PMID- 8346785 TI - Pattern of usage of the laryngeal mask airway. PMID- 8346787 TI - A method of fixing of laryngeal mask airways. PMID- 8346786 TI - The laryngeal mask airway and resuscitation. PMID- 8346788 TI - Alternative techniques for laryngeal mask airway insertion. PMID- 8346789 TI - The split laryngeal mask airway. PMID- 8346791 TI - General anaesthesia for caesarean section--noradrenaline response. PMID- 8346790 TI - Anesthetic drug allergies. PMID- 8346792 TI - Unexpectedly high spinal anaesthesia following failed extradural anaesthesia for caesarean section. PMID- 8346793 TI - Anaesthetic death of a child with a cold. PMID- 8346794 TI - Transverse myelitis following general anaesthesia. PMID- 8346795 TI - A source of artefact during general anaesthesia for magnetic resonance imaging. PMID- 8346796 TI - Infusion delays through multilumen catheters using standard syringe pumps. PMID- 8346797 TI - Reversal of atracurium after low dose tubocurarine. PMID- 8346798 TI - Increasing the likelihood of success of brachial plexus block. PMID- 8346799 TI - Prevention of bronchial intubation with RAE tube during adenotonsillectomy. PMID- 8346800 TI - Lignocaine sprays and cross infection. PMID- 8346802 TI - T-piece scavenging--the double-bag system. PMID- 8346803 TI - Confirmation of intravascular catheter placement by pulse oximetry following indocyanine green injection. PMID- 8346801 TI - The Whisperflow adjustable flow generator. PMID- 8346804 TI - The historic development of pain relief clinics. PMID- 8346805 TI - 1994 LabGuide. PMID- 8346806 TI - Histochemical identification of the striated muscle of the canine esophagus. AB - Histochemistry on the cervical, thoracic, and abdominal esophageal muscle of immature, young, and adult normal dogs revealed type IIA striated musculature in contrast to some other species. No other types or subtypes were observed. This suggests that esophageal muscle type is established at birth and does not vary or that any variation has been completed by 4 weeks-of-age unlike some canine limb musculature. PMID- 8346807 TI - An additional bone in the carpal region of raptorial birds. AB - In a series of 4 species of owls and 12 species of diurnal raptors, an additional bone was present bilaterally in the area of the carpus. Designating the bone as an "additional bone of the raptorial carpal region" is suggested pending appropriate embryological studies to determine the origin of the bone. Generally, the bone was present in owls and in diurnal raptors with relatively short, rounded wings, but was absent in species with longer, more tapered wings. The bone lies at the cranial edge of the carpal area near the radial carpal bone, and is fixed to the surrounding skeleton by ligaments. The tendon of the tensor patagium longus muscle has one slip that attaches to the additional bone and another that passes over its craniodorsal surface en route to insertion. Awareness of the occurrence of this bone in some raptors, but not others, is essential in clinical evaluation of wing injuries, as well as in forming a prognosis for the return to soundness, the potential for release, and, therefore, the life of an injured raptor. PMID- 8346808 TI - Ultrastructure of the rete testis in the cat (Felis domestica, L.). AB - The rete testis (RT) in the cat comprises three distinct and sequential parts: septal or adlobular; mediastinal and tunical parts. This last part is followed by the small extratesticular rete testis. The whole of the RT tubules and/or channels is lined by single low columnar and/or cuboidal epithelium with ultrastructural peculiarities of secretory and absorptive functions. The Golgi apparatus polarity (cis-trans surfaces), its relation with the long profiles of the ER, mainly with the rough ER, and presence of apical uncoated electrodense granules are suggestive of active release of macromolecules, probably glycoproteins. The absorptive function is proposed through the observation of a conspicuous microvacuolar-vesicular apical complex in epithelial cells. Moreover spermatozoa phagocytosis is also noticed, mainly in the septal part of the RT. PMID- 8346809 TI - [Anatomy of the development of the digestive tract and shape of the external body during the embryonic period of the goat (Capra hircus)]. AB - The purpose of this work has been to establish the pattern of prenatal growth and normal development of the digestive tract and annex glands during goat embryonic stages. 21 embryos with ages ranging from 14 to 34 days (1.69 to 5.90 cm CR) as determined by registering the mating time, were obtained by cesarean section. This material was histologically processed to obtain complete serial sections of the stomatodaeum, foregut, midgut, hindgut and cloaca. In this work, it is chronologically described the morphogenesis and histogenesis of the mouth, hypophysis, pharynx and its derivatives, stomach, intestine, liver, pancreas and cloaca. The results obtained establish chronological comparisons with the development of the lamb and gives information on the unitary origin of the gastric compartments in ruminants. PMID- 8346810 TI - Globule leukocytes and bovine parasitic bronchitis. AB - Globule leucocytes (GL) occur in the respiratory tract of cattle from foetuses to adult animals. Large numbers of this cell have been found in the lungs of cows both in normal lung and in the lungs of cows from various outbreaks of respiratory diseases, but the significance was not known. In the rat and in cattle, the occurrence of GL in the gastrointestinal and urinary tracts has been associated with parasitic infections. The relationship between the respiratory tract GL and Dictyocaulus viviparus infections in cattle was studied in three groups of parasite free calves experimentally infected with D. viviparus. Group 1 animals received single challenge infections. Group 2 had three subgroups (2a, 2b, 2c) which were either vaccinated and challenged (2a), given a single challenge (2b) or used as vaccinated controls (2c). Group 3 with four subgroups (3a, 3b, 3c, 3d) were either used as environmental controls (3a), vaccinated and repeatedly challenged (3b), given normal larvae of D. viviparus and repeatedly challenged (3c) or as a trickled group 3d. Although GL were found in infected calves, it was not possible to demonstrate a clear cut correlation between their presence or density and the method of exposure. PMID- 8346812 TI - [Mathematical models applied to the growth of the ovine stomach during intrauterine life]. AB - One hundred forty four ovine embryos and feti were used in an investigation to determine mathematical models describing the histomorphometric growth of tissues and compartments of the ruminant stomach. The results indicate that during prenatal life the diameter of the gastric chambers increase more slowly than the length. The tissue layers of the gastric walls, particularly the muscular tunic of all compartments demonstrated a uniform tendency toward more rapid development than the compartment walls proper. PMID- 8346811 TI - Actin filaments in the ruminal epithelium of cattle. AB - Phalloidin and immunogold labeling were used to localize actin filaments in the ruminal pilar epithelium of adult cattle on the light and electron microscopic level. Incubation with rhodaminyl-phalloidin permitted an overview of general actin distribution pattern. Distinct subcellular localization of actin was revealed with the biotin-streptavidin bridge technique in a postembedding procedure. Superior fixation of membranes and filaments was achieved with tannic acid-glutaraldehyde. Surface-etching prior to immunoincubation ensured restoration of actin immunoreactivity. Patterns of distribution in non keratinized and keratinized epithelial cells as well as in pericytes and endothelial cells point to cell-specific cytoskeletal and motile functions of actin filaments. PMID- 8346813 TI - [The topography of the skull and brain of the goat]. AB - This study, based on three goats, provides a radiographic projection of a median section of the brain and the skull. The method allows a topographic correlation of brain structures with the skull and surrounding osseous structures. A standard skull position, with the basic horizontal plane passing through the external acoustic meatus, and parallel to the floor of the skull, results in a method of localizing brain structures in specific transverse planes. This stereotaxic method allows investigators to account for variability in topography between animals in the localization of brain structures through external morphology. PMID- 8346814 TI - The structure of the harderian gland of the guinea fowl at embryonic and post embryonic stages. AB - The Harderian gland of the guinea fowl is a bright, pink and relatively large orbital organ situated at the ventromedial aspect of the orbit. It possesses a single duct that has its exit on the convex medial surface. The outline is irregular with its caudal half narrower than the rostral half, and possessing a slight constriction about the mid point. Histologically, the gland had been outlined with the existence of a large contorted lumen by day 18 of incubation. The surface epithelial lining showed two layers of cells all through and lymphocytes were also present. By day 19 of incubation, certain zones of the surface epithelium had become pseudostratified and some of these cells contained vacuoles indicative of secretory materials within their cytoplasm. By day 21, few definitive acini with lumina had been observed and at day 23, the epithelium had assumed only a single layer of cells that were tall columnar cells, except at the junctions of the folds. By day 24, the tunica propria seemed to have completely disappeared with the acini occupying every available space. Plasma cells were seen three days after hatching. PMID- 8346815 TI - Gross anatomy of the canine portal vein. AB - The gross anatomy of the portal vein of 21 dogs was studied by venous portography, corrosion casting, and gross dissection. The portal vein in all specimens originated by confluence of the cranial and caudal mesenteric veins. Its large tributaries were the splenic and gastroduodenal veins, which entered the portal vein between its origin and the hepatic porta. At the hepatic porta, the portal vein divided into a short right branch and a larger left branch. The right branch ramified in the caudate process of the caudate lobe and in the right lateral lobe of the liver. The left branch was essentially the continuation of the portal vein from which successive branches passed to each of the remaining lobes of the liver and the papillary process of the caudate lobe. PMID- 8346816 TI - Use of ketorolac and fentanyl during outpatient gynecologic surgery. AB - In healthy outpatients undergoing minor gynecologic surgery, the analgesic efficacy of ketorolac was compared to fentanyl and to a combination of the two analgesics. One hundred and nine patients were randomly selected to receive fentanyl 50-100 micrograms, ketorolac 30-60 mg, or a combination of fentanyl 50 100 micrograms and ketorolac 30-60 mg, intravenously (IV). Anesthesia was induced with midazolam 2 mg IV and propofol 1 mg/kg, IV, and maintained with propofol, 50 160 micrograms.kg-1.min-1, IV, and nitrous oxide 67% in oxygen via a face mask. Intraoperative anesthetic conditions, recovery times, and postoperative pain and side effects were evaluated. In the ketorolac group, 75% of patients required supplemental fentanyl intraoperatively (mean dose +/- SD, 47 +/- 54 micrograms), compared to only 19% (13 +/- 30 micrograms) and 18% (6 +/- 15 micrograms) of patients in the fentanyl and combination groups, respectively. In the ketorolac group, 74% of patients moved in response to surgical stimulation compared to only 16% and 19% of patients in the fentanyl and combination groups, respectively. Although there were no significant differences in intraoperative mean arterial pressure, heart rate, and oxygen saturation of hemoglobin values among the three treatment groups, the ketorolac group manifested significantly more rapid respiratory rates throughout the procedure compared with the fentanyl and combination groups. Recovery times, postoperative side effects, and pain scores, as well as postoperative analgesic and antiemetic requirements, were similar in all three treatment groups. However, the ketorolac group reported significantly higher pain scores in the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346817 TI - Isoflurane, compared to halothane or enflurane, causes increased lactate production but no transmural coronary steal during myocardial ischemia in swine. AB - We compared the effects of isoflurane, enflurane, and halothane on myocardial blood flow, function, and metabolism in normally perfused and ischemic regions of the swine heart. A model of single vessel incomplete occlusion was used so that the capacity of these anesthetics to cause transmural coronary steal could be tested. After median sternotomy, the left anterior descending coronary artery (LAD) was cannulated and autoperfused from the carotid artery. Systolic segment shortening was measured in the regions of the heart perfused by the LAD and left circumflex arteries. Regional myocardial blood flow was measured with radioactive microspheres. Blood was obtained from the anterior cardiac vein for measurement of lactate. Measurements were made during imposition of a stenosis on the perfusion circuit sufficient to decrease resting flow by 25%. The same stenosis was imposed during three treatment periods in a randomized and balanced cross over design. In one group of 12 swine, treatments were two doses of intracoronary adenosine and a control period. A second group of 12 were given 1.5% isoflurane, 2.18% enflurane, and 0.98% halothane. Heart rate, mean aortic pressure, and left atrial pressure were matched during the three treatments in each animal. Adenosine caused transmural steal resulting in diminished systolic segment shortening in the ischemic LAD region. During isoflurane, compared to halothane, the first derivative of left ventricular pressure with respect to time was greater by 28%, and systolic segment shortening in the normal left circumflex artery and ischemic LAD regions was greater by 27% and 31%, respectively. Subepicardial flow in the ischemic region was greater with isoflurane but subendocardial flow was unchanged. Lactate production during isoflurane was 52% and 76% greater than during halothane and enflurane, respectively. Our results indicate that isoflurane is not a sufficiently potent arteriolar vasodilator in swine to cause transmural steal. Although myocardial performance was superior with isoflurane in both ischemic and normally perfused regions, lactate production also increased, suggesting worsened ischemic metabolism. It is likely that the myocardial oxygen supply/demand ratio worsened with isoflurane because it caused less myocardial depression than the other anesthetics. PMID- 8346818 TI - Myocardial ischemia: a comparison between isoflurane and enflurane in coronary artery bypass patients. AB - Isoflurane may precipitate ischemia in patients with coronary artery disease, presumably via "coronary steal." We sought to examine whether myocardial ischemia is more common in patients with coronary artery disease receiving isoflurane (0.7%) than in a control group receiving enflurane (0.9%). Thirty-eight patients scheduled for coronary artery bypass surgery were randomly assigned one anesthetic and monitored for ischemia. All patients had ejection fractions of at least 45%. Extraneous causes of ischemia were controlled as much as possible: arterial blood pressure was maintained within 20% of baseline (primarily with phenylephrine), heart rate was maintained below 80 bpm, effects from endotracheal intubation were monitored, and measurements were made before incision. Electrocardiogram, transthoracic echocardiography, and coronary sinus lactate measurement were used to detect ischemia. Measurements were made after insertion of vascular catheters, after intubation, and after 20 min of breathing the inhaled anesthetic. During the awake period and after induction of anesthesia with fentanyl (25 micrograms/kg), there was no significant difference detected between the two groups in incidence of ischemia: 20% in the enflurane group and 22% in the isoflurane group (P = 0.38). After 20 min of receiving the inhaled anesthetic, the incidence of ischemia in the isoflurane group increased to 50%, whereas the incidence in the enflurane group was unchanged at 20% (P = 0.02). These results show that, even with strict control of hemodynamics, isoflurane is associated with more myocardial ischemia than is enflurane. PMID- 8346819 TI - The effect of phenylephrine bolus administration on left ventricular function during isoflurane-induced hypotension. AB - By using transesophageal echocardiography, we examined the effect of phenylephrine (PHE) bolus administration on left ventricular function in 16 patients with no known cardiovascular disease during isoflurane-induced hypotension. PHE was compared with norepinephrine (NE). The patients received an intravenous bolus of PHE (2 micrograms/kg) or NE (0.1 microgram/kg) in random order. The second substance was administered after levels of arterial blood pressure and heart rate returned to baseline levels. We determined fractional area change, end-systolic wall stress, and rate-corrected mean velocity of circumferential fiber shortening. Both substances effectively restored arterial blood pressure. However, after PHE, fractional area change decreased from 0.45 to 0.31 (mean) and rate corrected mean velocity of circumferential fiber shortening from 0.88 to 0.57 circumference/s, whereas both variables remained unchanged in response to NE. End-systolic wall stress increased after PHE and NE from 47.4 to 91.2 and from 54.0 to 65.2 10(3) dyne/cm2, respectively. We conclude that phenylephrine, given as intravenous bolus to patients under isoflurane hypotension, causes a transient impairment of left ventricular systolic performance. PMID- 8346820 TI - Nitrous oxide constricts epicardial coronary arteries in pigs: evidence suggesting inhibitory effects on the endothelium. AB - Nitrous oxide increases peripheral vascular tone in animals and humans and constricts epicardial coronary arteries in dogs. Current studies sought both to determine whether nitrous oxide caused epicardial coronary artery constriction in a second animal species, pigs, and to investigate mechanisms. Left anterior descending coronary artery diameters were measured by using computer-assisted angiography in intact pigs anesthetized with ketamine and fentanyl. In separate experiments, isolated porcine coronary arteries were used to assess nitrous oxide effects on both vascular tone and norepinephrine overflow. Agonist-induced increases in [Ca2+]i were estimated in cultured porcine coronary endothelial cells. Nitrous oxide caused epicardial coronary artery vasoconstriction in vivo by about 20%. Nitrous oxide did not affect endothelium-dependent relaxations and contractions in isolated vessels. Norepinephrine overflow was increased but only in vessels with endothelium. The anesthetic attenuated Ca2+ mobilization in endothelial cells. We conclude that nitrous oxide induces epicardial coronary artery constriction in pigs and suggest that the mechanism may involve the inhibition of endothelium-dependent norepinephrine turnover. PMID- 8346821 TI - Lower extremity hypothermia is beneficial during infra-renal aortic cross clamping in pigs. AB - The effects of lower extremity hypothermia during aortic cross-clamping are unknown. To compare the effects of lower extremity hypothermia with normothermia during aortic cross-clamping, two groups of six (25-40 kg) anesthetized pigs had their aortas cross-clamped below the renal arteries for 2 h. The cold group had their lower extremities cooled during cross-clamping to a quadriceps muscle temperature of 28 degrees C by using convective cooling. The warm group had the quadriceps muscle temperature maintained at 38 degrees C with convective warming. Saline, 0.9%, was used to maintain the pulmonary capillary wedge pressures at 5 mm Hg in both groups. Reperfusion of the lower extremities resulted in a small but significant decrease in the blood temperature from 36.6 +/- 0.3 degrees C (mean +/- SE) to 35.6 +/- 0.3 degrees C 1 min after reperfusion in the cold group, but did not change the blood temperature in the warm group. Both the cardiac output and the lower extremity arterial flow were greater in the cold group at 1 and 5 min after cross-clamp release. Also one pig in the warm group required resuscitation with 1 mg of epinephrine intravenously to treat severe hypotension and myocardial depression after cross-clamp release. We conclude that hypothermia of the lower extremities may be beneficial for surgery involving aortic cross-clamping. PMID- 8346822 TI - Separation of myocardial versus peripheral effects of calcium administration in normocalcemic and hypocalcemic states using pressure-volume (conductance) relationships. AB - This study used left ventricular pressure-volume (conductance) relationships to separate the effects of calcium administration on myocardial performance and peripheral vasoconstriction in normocalcemic and hypocalcemic states. Hypocalcemia was produced in anesthetized dogs with intravenous citrate-phosphate dextrose until serum [Ca2+] was approximately 0.7 mmol/L. Calcium (CaCl2) bolus (5 mg/kg) was administered during normocalcemia (n = 6) and hypocalcemia (n = 6), and data were collected at 1, 5 and 10 min after CaCl2 administration. During normocalcemia, CaCl2 administration increased [Ca2+] 19% at 1 min and was accompanied by a 47% (P < 0.05) decrease in left ventricular contractility (i.e., end-systolic elastance or E(lves)) and a 13% (P < 0.05) increase in systemic vascular resistance. At 5 and 10 min, serum [Ca2+] and the hemodynamic variables began to return to the baseline values. During hypocalcemia, E(lves) decreased 25% (P < 0.05), but after CaCl2 bolus, it increased to baseline levels and remained there during the 10-min period. Hypocalcemia and the CaCl2 bolus did not significantly affect SVR. In conclusion, these studies suggest that the indications for the use of calcium should depend on the initial serum level of ionized calcium. PMID- 8346823 TI - Parental knowledge and attitudes toward discussing the risk of death from anesthesia. AB - There is considerable debate as to the extent of disclosure of risks when obtaining informed consent for anesthesia, especially when discussing with parents the rare risk of death of healthy children about to undergo elective, outpatient surgery. In Part I, we attempted to determine parents' knowledge about the risks of anesthesia as well as their thoughts toward either hearing, or not hearing, about the risk of death. In the first part of our study, 115 parents completed questionnaires before speaking with the anesthesiologist. Ninety-six (87%) wanted to know the chances of death as a result of anesthesia, whereas 14 (13%) did not. Seventy-five (68%) parents knew that this risk was "extremely rare," 21 (19%) believed that it occurs "once in a while," and 14 (13%) thought there was "no chance." Eighty-two (74%) parents wanted to know "all possible risks," 26 (24%) wanted to know only "those that are likely to occur," and 3 (2%) wanted to know only about those that would "result in significant injury." Mothers were more likely to want to hear all possible risks, whereas fathers were more likely to want to know only about those that are likely to occur (P = 0.001). Otherwise, responses were not influenced by the sex of the parents, the age of the child, or whether the child or any siblings had had surgery in the past. In Part II, a separate group of 121 parents were surveyed after participating in the preanesthetic discussion with the anesthesiologist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346824 TI - Performance of pediatric resuscitation bags assessed with an infant lung simulator. AB - Many pediatric self-inflating bags are equipped with pressure relief (pop-off) valves to prevent barotrauma. We participated in a resuscitation in which a valve malfunction briefly caused inadequate ventilation. The pop-off valve was seated in an intermediate position between open and closed settings. To investigate this problem, we assessed the performance of several commonly used pediatric self inflating bags using an infant lung simulator (D, B & M, Redlands, CA). Bags were deflated using a range of inspiratory times (TI), delivered tidal volumes, peak proximal airway pressure (Pp), and peak distal pressure (lung pressure, Pd). When the pop-off valve was set in the open position, Pp ranged from 42 cm to 105 cm H2O, although P(d) never exceeded 45 cm H2O. The mean difference between Pp and P(d) decreased from 14.2 +/- 1.1 cm H2O at TI = 0.2 s to 6.1 +/- 0.5 cm H2O at TI = 1 s. Inflation of all DMR (disposable) and PMR (nondisposable) bags in the intermediate valve position produced marked air leakage through the valve, with delivered tidal volumes of only 92 +/- 13 mL (DMR) for TI < 0.5 s, and unrecordable tidal volumes (< 50 mL) for both DMR and PMR self-inflating bags for TI > 0.6 s. A wide range of delivered tidal volumes was observed among all bags examined. We conclude that both DMR and PMR bags can be placed inadvertently in an intermediate valve position that can produce disastrous hypoventilation during resuscitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346825 TI - Suppression of nociceptive responses by spinal mu opioid agonists: effects of stimulus intensity and agonist efficacy. AB - To determine the influence of stimulation intensity on dose-response curves of three analgesics in halothane-anesthetized rats, continued immersion of the tail in 52.5 degrees C or 60 degrees C water for 15 s results first in a nociceptive reflex tail movement (tail flick = 2.8 +/- 0.4 s and 1.4 +/- 0.2 s, respectively), and a progressive increase in arterial blood pressure (delta BP = 21 +/- 1 and 24 +/- 1 mm Hg) and heart rate (delta HR = 27 +/- 2 and 32 +/- 2 beats/min). Intrathecally administered mu opioids, morphine (MOR), sufentanil (SUF), and [D-Ala2-N-Phe4,Gly-ol]-enkephalin (DAG), produced a dose-dependent inhibition of the tail flick and BP response with the relative activity being SUF = DAG > MOR. Although the magnitude of the response evoked by increasing stimulus intensity from 52.5 degrees C to 60 degrees C was increased only mildly (suggesting that both represented essentially supramaximal stimuli), this increase in stimulus intensity resulted in a significant rightward shift in the dose-response curves (decrease in apparent potency) of the three agonists, with the magnitude of the shift being MOR > SUF = DAG. Thus, the dose ratio (ED50 at 60 degrees C/ED50 at 52.5 degrees C) for these three analgesics given intrathecally on the tail flick and BP response was, respectively, 3.7 +/- 0.9 and 6500 +/- 465 for MOR; 0.5 +/- 0.9 and 2.4 +/- 0.9 for SUF; and 0.5 +/- 1.2 and 7.0 +/- 0.9 for DAG. Unlike SUF and DAG, with the 60 degrees C stimulus, the highest dose of MOR failed to abolish the BP and heart rate response. Previous work with an irreversible antagonist to define receptor occupancy requirements showed that the relative efficacy was SUF = DAG >> MOR. The present studies thus confirm the pharmacodynamically based prediction that for a given change in stimulus intensity, anesthetics with a high efficacy (DAG and SUF) show less shift in their dose response curves with a given increase in stimulus intensity than an agonist with low efficacy (MOR). PMID- 8346826 TI - Continuous spinal anesthesia with a microcatheter and low-dose bupivacaine decreases the hemodynamic effects of centroneuraxis blocks in elderly patients. AB - This prospective randomized study was designed to investigate the hemodynamic effects and quality of continuous spinal anesthesia (CSA) after rapid injection of a low dose of 0.5% bupivacaine through a 32-gauge microcatheter. The method was compared with continuous epidural (CEA) and single-dose spinal anesthesia (SSA). Seventy-seven elderly patients (ASA II-III) ranging from 57 to 94 yr old and undergoing lower limb surgery were assigned to CSA (n = 26), CEA (n = 26), and SSA groups (n = 25). In all three groups, mean arterial pressure (MAP) and heart rate (HR) were assessed continuously for 30 min after initial injection, as well as after every reinjection of local anesthetic in the CSA and CEA groups. Bupivacaine (0.5%) was used as a local anesthetic. The initial doses were 1 mL of CSA, 10 mL of CEA, and 3 mL of SSA. The reinjection doses were 1 mL of CSA and 5 mL of CEA. In the CSA group, MAP did not decrease, whereas in the CEA group, the maximum decrease was 15% +/- 3% (mean +/- SEM) for the initial injection, 12% +/- 2% for the first repetition, and 13% +/- 2% for the second repetition. In the SSA group, the largest decrease of MAP was 19% +/- 2%. All changes of MAP in the CEA and SSA groups were significantly larger compared with CSA group (P < 0.05). A total of seven patients in these two groups needed vasopressors due to a decrease of MAP of more than 30% from baseline values. Heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346828 TI - Malignant hyperthermia: a review of published cases. AB - Malignant hyperthermia (MH) is triggered by many anesthetics. This study investigates the epidemiology of MH, its association with various drugs, and mortality rates. Five hundred three cases of MH were reported. MH patients were demographically similar worldwide. Pediatric (52.1%, age < 15 yr) and male (65.8%) MH patients exceed the general surgical population. Congenital defects and musculoskeletal surgical procedures were associated clearly with MH. Previous uneventful anesthesia (20.9%) and absence of positive family history (75.9%) were common. Case fatality rates have decreased with time to 10% since 1985. This decline is partly and independently due to dantrolene therapy, as well as to better vigilance and awareness on the part of the anesthetic community. PMID- 8346827 TI - Isoflurane-induced splanchnic sympathectomy. AB - To ascertain whether isoflurane produces a peripheral splanchnic sympathectomy as compared to fentanyl or pentobarbital anesthesia, 12 mongrel dogs (30-45 kg) were allocated randomly to one of three anesthetic test groups, tracheally intubated, surgically prepared, and subjected to unilateral electrical stimulation of the greater splanchnic nerve. Anesthetically, Group 1 animals (n = 4) received pentobarbital, Group 2 animals (n = 4) were administered fentanyl, and Group 3 animals (n = 4) received isoflurane. Stimulation continued for 90 min. Each second of stimulation consisted of 20 stimuli of 0.5 minimum alveolar anesthetic concentration duration and 5 V intensity, delivered during a 0.2-s interval, followed by an 0.8-s pause. To assess splanchnic sympathetic responses, mean arterial blood pressure, heart rate, pulmonary artery diastolic, cardiac output, adrenal blood flow, adrenal and arterial norepinephrine (N) and epinephrine (E) were obtained before and at 5, 10, 15, 30, 45, 60, and 90 min during stimulation. In Group 1 animals (pentobarbital), electrical stimulation elicited marked increases in mean arterial blood pressure, pulmonary artery diastolic, and cardiac output (P < 0.001). Examination of the adrenal effluent, which was exteriorized from the animal during the protocol, revealed that adrenal blood flow, adrenal vein N and E concentrations dramatically increased (P < 0.0001). Arterial N and E concentrations remained unchanged. Results of Group 2 animals (fentanyl) were similar to those of Group 1; mean arterial blood pressure, pulmonary artery diastolic, and cardiac output increased (P < 0.005). Adrenal blood flow, adrenal vein N and E increased dramatically (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346829 TI - A clinical comparison of bronchial cuff pressures in three different designs of left double-lumen tubes. AB - This study compared the bronchial cuff pressures and volumes required by three different designs of disposable left double-lumen tubes during clinical one-lung ventilation in 48 patients having right thoracotomies. Mallinckrodt, Rusch, and Sheridan design tubes (n = 16 for each) were studied in a randomized fashion using Fr# 35, 37, 39, and 41 sizes (n = 12 for each size). There were no pressure/volume differences between brands during bronchial cuff inflation before endotracheal intubation. Intraoperatively, the Sheridan design required significantly higher mean bronchial cuff pressures: [27.9 cm H2O +/- 17 cm H2O (SD)] than either the Mallinckrodt [17.6 cm H2O +/- 8.5 cm H2O (P = 0.012)] or Rusch [14.1 cm H2O +/- 8.6 cm H2O (P = 0.010)] to achieve one-lung isolation. During prolonged one-lung ventilation, the potential for trauma to the bronchus may be reduced with a Mallinckrodt or Rusch design of left double-lumen tube. PMID- 8346831 TI - The selection of a residency program: prospective anesthesiologists compared to others. AB - A study was undertaken to investigate factors important to senior medical students, particularly prospective anesthesiology residents, in selecting a residency program. A previously published questionnaire was used to determine whether previous findings could be replicated. One hundred ninety-seven senior medical students rated the importance of 22 items in their selection of a residency program. Factors were ranked nearly identically as in the previous study. Factors rated as most important were "diversity of training experience" as well as "house officer satisfaction," whereas items about treating patients with the acquired immunodeficiency syndrome were rated as least important. There were gender differences that showed women assigned more importance to having a manageable case load, call schedules, and geographic location. Prospective anesthesiology residents perceived "prestige" of the program, and the department as significantly more important than did prospective nonanesthesiology residents. The replication of results with regard to the overall ranking of factors demonstrates the reliability of the results. Resident selection committees need to focus on the issue of quality of training, the impression made by the interviewers, and include satisfied residents as part of the interview process. PMID- 8346830 TI - Intravenous lidocaine as a suppressant of coughing during tracheal intubation in elderly patients. AB - The effects of intravenously administered lidocaine on cough suppression in elderly patients over the age of 60 yr during tracheal intubation under general anesthesia were evaluated in two studies. In the first study, 100 patients received a placebo of either 0.5, 1.0, 1.5, or 2.0 mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1.5 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P < 0.01). In the second study, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in Study 1. The incidence of coughing decreased significantly (P < 0.01) when 2 mg/kg lidocaine was injected intravenously between 1 min and 3 min before attempting intubation. The cough reflex was almost entirely suppressed by plasma concentrations of lidocaine in excess of 4 micrograms/mL. The results suggest that intravenous administration of lidocaine is effective in suppressing the cough reflex during tracheal intubation in elderly patients under general anesthesia, but that relatively high plasma concentrations of lidocaine may be required for suppression of coughing. PMID- 8346832 TI - Diltiazem reduces the dose requirement for nitroprusside-induced hypotension. AB - The efficacy of diltiazem, a calcium channel blocker, for reducing the dose requirement for nitroprusside-induced hypotension was studied in 20 healthy patients during spine fusion for scoliosis. Anesthesia included methohexital (3 mg/kg followed by 3 mg.kg-1.h-1 intravenously), nitrous oxide, and alfentanil (40 micrograms/kg, followed by 0.7 microgram.kg-1.min-1 intravenously). Patients were assigned randomly to two groups, receiving either nitroprusside alone or nitroprusside and diltiazem (bolus of 80 micrograms/kg with two consecutive infusions of 4.5 micrograms.kg-1.min-1 during the first 30 min and then 1.3 micrograms.kg-1.min-1). Nitroprusside was used to maintain mean arterial pressure at 55-60 mm Hg in both groups. Hypotension was obtained in similar times, 4 min in the group receiving nitroprusside alone (range, 1-8 min) and 2 min in the group receiving nitroprusside and diltiazem (range, 1-8 min). Nitroprusside administration lasted 186 +/- 17 min (mean +/- SEM) in the group receiving nitroprusside alone and 214 +/- 26 min (mean +/- SEM) in the other group (NS). After hypotension, arterial blood pressure returned to its initial value in a time of 7 min in the group receiving nitroprusside alone (range, 5-9 min) and 9 min in the group receiving nitroprusside and diltiazem (range, 7-13 min) (NS). Cumulative doses of nitroprusside were larger in the group receiving nitroprusside alone (0.47 +/- 0.07 mg/kg; mean +/- SEM) than in the other group (0.24 +/- 0.05 mg/kg; mean +/- SEM) (P < 0.01). Significant increase in plasma thiocyanate concentration, cardiac index, and heart rate was observed only in the group receiving nitroprusside alone, but no intergroup differences were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346833 TI - Comparative myocardial depressive effects of propofol and thiopental. AB - To compare the direct myocardial effects of thiopental and propofol, concentration-contractility curves were determined by using an isolated guinea pig left atrial preparation. Contractility was measured as peak twitch tension, maximum rate of contraction (dT/dt), and maximum rate of relaxation (-dT/dt). Drug concentrations ranged from 56 microM (10 micrograms/mL) to 2800 microM (500 micrograms/mL) propofol and 3.8 microM (1 microgram/mL) to 190 microM (50 micrograms/mL) thiopental. Data were fitted to a sigmoidal inhibitory pharmacodynamic model in which an increasing incremental drug concentration is needed to cause a consistent incremental effect. Comparisons were then made of the drug concentrations at which a 50% inhibition in contractility was noted (IC50). To compare drugs on an equi-anesthetic basis, comparisons also were made between IC50 values normalized to anesthetic concentrations needed to produce anesthesia (67.8 microM and 28.1 microM for thiopental and propofol, respectively). Data from seven atrial preparations for thiopental and seven atrial preparations for propofol were analyzed. The IC50 (microM) for peak twitch tension were 20.9 +/- 6.3 and 96.6 +/- 10.1 (P < 0.05), for dT/dt were 21.1 +/- 5.9 and 86.9 +/- 8.3 (P < 0.05), and for -dT/dt were 21.0 +/- 6.1 and 84.3 +/- 9.2 (P < 0.05) for thiopental and propofol, respectively. When the normalized IC50 were compared, the differences between anesthetics became greater. For guinea pig left atria in vitro, thiopental is a more potent myocardial depressant than propofol, especially when compared relative to anesthetic potencies; neither anesthetic preferentially affects peak twitch tension, maximum rate of contraction, or maximum rate of relaxation. PMID- 8346834 TI - Effect of anesthetics on neuropathologic sequelae of status epilepticus in rats. AB - We compared the efficacy of four different classes of anesthetics to arrest the progression of brain damage after chemoconvulsant-induced seizures in rats. In two series of experiments, ventilated, paralyzed Long-Evans rats were subjected to 30 or 45 min of continuous seizures induced by intravenous (IV) mercaptopropionic acid (MPA) or inhaled flurothyl, respectively. In the first series, seizures produced with MPA were treated with: 1) thiopental, 15 mg/kg IV bolus (controls); 2) thiopental, 27 mg/kg IV followed by 20.9 mg.kg-1.h-1 for 2 h; 3) isoflurane 4% inhaled concentration for 1 min followed by 1%-2% for 2 h; 4) ketamine 30 mg/kg IV followed by 9.12 mg.kg-1.h-1 for 2 h; 5) midazolam 25 mg/kg IV followed by 9.7 mg.kg-1.h-1 for 2 h. In a second series, seizures were produced by flurothyl and, based on suggestive results in the MPA series, control rats were compared with rats receiving midazolam 25 mg/kg IV followed by 9.7 mg.kg-1.h-1. In all instances, seizure activity, recorded by electroencephalograph, stopped with anesthetic treatment. In MPA-treated rats extranigral damage was mild, with no differences apparent between anesthetics. Control animals sustained severe lesions in the substantia nigra pars reticulata (SNPR). No statistically significant differences between anesthetic groups were present, although an effect was suggested for midazolam to decrease SNPR lesional area (P = 0.06). In flurothyl-treated rats, there were significant reductions in SNPR neuropathologic grade (P = 0.025) and lesional area (P = 0.025) with midazolam. We conclude that midazolam attenuates postseizure SNPR damage in rats. PMID- 8346835 TI - High levels of carbon monoxide are produced by electro-cautery of tissue during laparoscopic cholecystectomy. AB - Pyrolysis of tissue in a hypoxic environment can produce carbon monoxide. The atmosphere of the peritoneal cavity is rendered hypoxic during laparoscopic cholecystectomy by insufflation with 100% carbon dioxide. To determine whether carbon monoxide is produced by electrocautery of tissue during laparoscopic cholecystectomy, nine patients undergoing this procedure had the insufflation gas after use of electrocautery analyzed for carbon monoxide. Blood was analyzed for carboxyhemoglobin in these same patients to determine whether carbon monoxide was being absorbed in dangerous amounts. Carbon monoxide was present in the peritoneal cavity 5 min after use of electrocautery was initiated at a median concentration of 345 ppm (range 25-1600 ppm), and at the end of surgery at a concentration of 475 ppm (range 100-1900 ppm). This was well in excess of the 35 ppm upper limit for a 1-h exposure set by the Environmental Protection Agency. The carboxyhemoglobin concentrations (mean +/- SD) were the same at the beginning (1.3% +/- 0.7%), end (1.2% +/- 0.7%), and the day after surgery (1.1% +/- 0.6%). Although there was no evidence of significant absorption of carbon monoxide in these patients, care should be taken to scavenge the gases produced by cautery of tissues to avoid operating room contamination during laparoscopic surgery. PMID- 8346837 TI - Influence of inhaled anesthetics on the pharmacokinetics and pharmacodynamics of morphine. AB - We determined the magnitude and duration of the effect of morphine (1.0 mg/kg intravenous bolus) on isoflurane and halothane minimum alveolar concentration (MAC) in six dogs anesthetized on two occasions in cross-over fashion. Plasma morphine concentration-time profiles and changes in PaCO2 were determined after morphine injection. After morphine injection, the end-tidal anesthetic dose was manipulated over the course of a 4-h observation period to account for the decline in plasma morphine concentration and to maintain an anesthetic level equivalent to 1.0 MAC isoflurane or halothane alone. Morphine decreased the MAC of halothane and isoflurane. The magnitude of MAC decrease was related to time after morphine injection and was similar for a given time with both halothane and isoflurane. For example, at 28.8 +/- 3.6 (mean +/- SE) and 34.8 +/- 6.3 min after morphine injection, the MAC for halothane and isoflurane were reduced by 35.7% +/ 4.5% and 39.3% +/- 3.4%, respectively. By 4 h after morphine injection, the MAC reduction for both anesthetics was less than 10% in most of the animals. Except for systemic clearance of morphine during halothane and isoflurane (40.1 +/- 6.1 and 53.7 +/- 5.6 mL.min-1.kg-1, respectively), there were no differences in disposition kinetics of free morphine associated with the two inhaled anesthetics. Morphine increased PaCO2 to a similar degree with both halothane (from 42.2 +/- 2.1 mm Hg to 55.6 +/- 2.3 mm Hg) and isoflurane (46.2 +/- 2.4 mm Hg to 55.3 +/- 2.1 mm Hg). Respiratory depression was abolished by noxious stimulation (tail clamp) and naloxone in all animals with both anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346836 TI - The impact of streptozotocin-induced diabetes on the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetics in the rat. AB - We designed experiments to examine the effects of insulin-dependent diabetes mellitus on the anesthetic requirements for volatile anesthetics. A standard tail clamp technique was used to determine minimum alveolar anesthetic concentrations for halothane, enflurane, and isoflurane in spontaneously breathing rats. Three groups of animals were used: 1) diabetic rats (12 wk after induction of diabetes with streptozotocin, 50 mg/kg, single dose, intravenously), 2) insulin-treated (7 U extended insulin zinc suspension per day, subcutaneously, beginning 5 wk after streptozotocin treatment) diabetic rats, and 3) control rats. The minimum alveolar anesthetic concentration values of the control animals were 1.16 +/- 0.02 vol% for halothane, 2.25 +/- 0.05 vol% for enflurane, and 1.42 +/- 0.04 vol% for isoflurane. Minimum alveolar anesthetic concentration was reduced by 23% for halothane (0.90 +/- 0.06 vol%), by 18% for enflurane (1.85 +/- 0.07 vol%), and by 17% for isoflurane (1.18 +/- 0.04 vol%) in diabetic rats. Insulin treatment restored the anesthetic requirement to control levels for all three anesthetics. These data from the rat model indicate that uncontrolled diabetes lowers anesthetic requirements significantly. PMID- 8346838 TI - Folinic acid protection against hematopoietic depression induced by nitrous oxide in rats. AB - We studied the degree of hematopoietic depression and spontaneous recovery of depressed hematopoietic cells with 50% nitrous oxide-oxygen inhalation for 6 or 12 h in 120 Sprague-Dawley rats. Bone marrow and blood were sampled serially immediately after, 1 day, 3 days, and 1 wk following nitrous oxide inhalation. After 1 wk of culturing of hematopoietic stem cells, the number of the colony forming units of granulocytes and monocytes and the colony-forming units of T lymphocytes grown from bone marrow and blood were counted. There was no change in the number of colonies immediately after inhalation compared with the control group, but there was a significant decrease in the number of colonies 1 and 3 days after inhalation (P < 0.001), and 1 wk after inhalation, there was spontaneous recovery without any treatment. Nitrous oxide may depress the early phase of differentiation of hematopoietic stem cells such as granulocytes, monocytes, and lymphocytes as well as erythrocytes. Also, the degree of suppression was more intense after 12 h than after 6 h of inhalation. That is, the length of inhalation time corresponds to the intensity and rapidity of suppression. To evaluate the protective effect of folinic acid against hematopoietic depression, folinic acid (0.1 mg/0.3 mL) was injected intraperitoneally before or after nitrous oxide inhalation. The groups injected with folinic acid showed significant increase in the number of colonies, especially in the group receiving folinic acid 12 h and 1 h before nitrous oxide inhalation (P < 0.001). Pretreatment with folinic acid may prevent the hematopoietic depression caused by the prolonged and repeated use of nitrous oxide. PMID- 8346839 TI - Preemptive analgesia--treating postoperative pain by preventing the establishment of central sensitization. PMID- 8346840 TI - Plasma cholinesterase: gene and variations. AB - The traditional tests that have been used for the past 30 yr to determine plasma cholinesterase phenotype--measurement of esterase activity with a variety of substrates, dibucaine inhibition, fluoride inhibition, and Ro2-0683 inhibition- are inadequate for identifying some variants of this enzyme and leave many cases of prolonged response to succinylcholine unexplained. The application of the techniques of molecular genetics has permitted precise identification of plasma cholinesterase variants and has resulted in the discovery of previously unrecognized variants. It is now possible, in cases of prolonged response to succinylcholine resulting from genetically determined alterations in plasma cholinesterase, to ascertain the nature of the mutations in the alleles, and from them to deduce the structural changes in the enzymes responsible for the impairment in drug metabolism. PMID- 8346841 TI - Reduction of jugular venous oxygen saturation coincidental with electroencephalographic abnormality. PMID- 8346842 TI - Fentanyl transdermal system overdose secondary to cutaneous hyperthermia. PMID- 8346843 TI - Is mivacurium chloride effective in electroconvulsive therapy? A report of four cases, including a patient with myasthenia gravis. PMID- 8346844 TI - Respiratory obstruction in a patient with Melkersson-Rosenthal syndrome. PMID- 8346845 TI - Continuous caudal epidural bupivacaine infusions in children. PMID- 8346846 TI - An algorithm for use of the laryngeal mask airway during failed intubation in the patient with a full stomach. PMID- 8346847 TI - Glass ampules. PMID- 8346848 TI - The esophageal detector device in the morbidly obese. PMID- 8346849 TI - The increase in plethysmographic amplitude due to the clipping of the vein of Galen aneurysm. PMID- 8346850 TI - Severe deformation of a small-gauge spinal needle. PMID- 8346851 TI - Perioperative serum bupivacaine levels after topical bladder anesthesia for bladder biopsy. PMID- 8346852 TI - Risk of cerebellar tonsillar herniation after diagnostic lumbar puncture in pseudotumor cerebri. PMID- 8346853 TI - Fiberoptic tracheal intubation through the laryngeal mask in an awake patient with cervical spine injury. PMID- 8346854 TI - Postoperative ulnar nerve palsy--is it an unpreventable complication? PMID- 8346855 TI - Peroneal palsy after epidural analgesia. PMID- 8346856 TI - Limitations of somatosensory evoked potentials for quantitating isolated nerve block. PMID- 8346857 TI - What is general anesthetic action? PMID- 8346858 TI - Intraoperative aspiration pneumonitis and the laryngeal mask airway. PMID- 8346859 TI - Intermittent throat tightness in a 37-year-old woman. AB - Intermittent throat tightness with dysphagia can be a complaint with numerous potential underlying causes. It was useful to think of this patient's complaints as secondary to an allergic, neuromuscular, or mechanical/structural disorder. Dysphagia can usually be separated into two broad categories according to location: oropharyngeal or esophageal. The patient typically can help one localize the area of involvement by pointing to the area where the difficulty in swallowing is felt to be present. This patient pointed to the throat area. Helpful diagnostic studies in the evaluation of oropharyngeal dysphagia include barium swallow with cine-esophagogram, rhinopharyngoscopy, or upper gastrointestinal endoscopy. It was interesting that this patient was referred to the Allergy Service because a physician felt that intermittent laryngeal angioedema was also a possible consideration. It is known that dysphagia, hoarseness, and sensations of throat tightness or closing frequently accompany this entity. The finding of a palpable thyroid was the clue that further evaluation of this organ was also indicated. Alfonso et al have reported on tracheal or esophageal compression secondary to benign thyroid disease. In their series, goiter, though previously felt to be associated with a low incidence, was reported to have an overall high incidence. Of the several types of thyroid disease encountered, they noted thyroiditis was associated with the highest likelihood of compression and a 67% frequency of associated obstruction. Our patient's scan and uptake findings are consistent with thyroiditis although multinodular goiter may occasionally show similar results. This case reminds us that in the differential of laryngeal angioedema and complaints associated with the throat or referred in the throat area, local extrinsic compression secondary to masses should be included. In this patient, a goiter, of which the extent of gland enlargement may not be fully appreciable on physical examination, was determined to be the etiology of her complaints. She was placed on a thyroid hormone suppression treatment regimen. At a followup visit several months later, she noted marked improvement of her symptoms with resolution of her dysphagia and episodes of throat tightness. PMID- 8346860 TI - Administration errors with a conventional metered dose inhaler versus a novel breath actuated device. AB - Metered dose inhalers are difficult for patients to use. A device that eliminates coordination and timing of actuation may simplify the use of metered dose inhalers. This trial compared (1) number of errors made and (2) specific errors made between the conventional press and breathe metered dose inhaler (MDI) and the novel breath actuated Autohaler inhalation device in 24 subjects. We studied the use of each device in 12 patients trained and experienced in using an MDI and in 12 volunteers who had never been exposed to any inhalation device. We observed that even experienced patients continue to have difficulty with the coordination and timing of metered dose inhalers. The volunteer group had equal difficulty with both devices but it appeared that it was easier for them to learn how to use the breath actuated device than the MDI. PMID- 8346861 TI - Food specific IgE antibodies: a comparative study of AlaSTAT and Pharmacia RAST Phadebas CAP systems in 49 patients with food allergies. AB - Forty-nine sera from patients with food allergies confirmed by challenge and of 14 with suspected allergy were assayed with the DPC AlaSTAT liquid phase EIA and the Phadebas RAST CAP radioimmunoassay (RIA). Twenty-two foods were tested (four animals, 18 vegetables). Controls were performed on nonatopic subjects (N = 8). Specificity was 100%. Concordance RAST CAP/AlaSTAT was 79.6%; prick tests/AlaSTAT: 76%; prick tests/RAST CAP: 73.9%. AlaSTAT detected specific IgE even in sera with low total IgE (< 60 KU/L), while RAST CAP was inconclusive. Dilution studies and reproducibility were excellent. AlaSTAT EIA compares favorably with the Phadebas RAST CAP RIA for measurement of food-specific IgE antibodies. PMID- 8346862 TI - Allergist influence on asthma care. AB - In 1989, the hospitalization rate for asthma at our institution had increased 23%. To evaluate possible reasons for this we examined all new patients seen in our clinic between June, 1985 and June, 1986. A second assessment of the same patients between June, 1987 and June, 1988 was also performed. Two-hundred nine patients were seen for asthma in 1986. Analyzed by follow-up care provider, care by an allergist (CA), and nonallergist care (NAC), at baseline patients had similar hospitalization (CA = 37%, NAC = 40%) and emergency room (CA = 61%, NAC = 45%) visit rates. At follow-up (1988), there was a significantly higher hospitalization rate in the NAC group (35%) than in the CA group (13%). Emergency room visits during the previous year were also significantly greater in the NAC group (47%) compared with the CA group (18%). Major differences in drug therapy between 1986 and 1988 included a marked increase in the utilization of inhaled corticosteroids and sodium cromolyn in the maintenance therapy of patients followed by an allergist. The use of spacer devices for inhalers and home peak flow meters also increased significantly in the CA group. Oral corticosteroid use increased similarly in both groups. Although there is an overall increase in admissions for asthma at our institution in 1989, these data suggest that continued follow-up care by an allergist is associated with a decreased hospital admission and emergency room visit rates when compared with care given by a generalist. PMID- 8346863 TI - Seasonal allergic rhinitis and antihistamine effects on children's learning. AB - Children suffering from seasonal allergic rhinitis and matched normals were instructed on the use of a didactic computer simulation in a realistic classroom situation. Groups of atopic children received different treatments before instruction; ie, sedating (diphenylhydramine HCl) or nonsedating (loratadine) antihistamines or placebo. All returned after 2 weeks for an examination measuring factual and conceptual knowledge and the application of a learned strategy. Examination results showed large and consistent impairing effects of the allergic reaction on prior learning. Both the placebo and diphenhydramine groups learned significantly less than normal controls. The loratadine group's learning performance was superior to either of the other atopic groups' but still inferior to the normals'. Our conclusions are that the allergic reaction reduces learning ability in children and that this effect is partially counteracted by treatment with loratadine and aggravated by diphenhydramine. PMID- 8346864 TI - Falafel burger anaphylaxis due to sesame seed allergy. AB - With the increasing demand for vegetarian food the consumption of vegetable burgers as an alternative to beef burgers has now become widespread. Since products of this kind are often not provided with a clear description of their components or ingredients, potential allergens generally cannot be identified by the consumer. Their ingestion, however, may lead to severe allergic reactions in sensitized individuals. Here we describe nine systemic allergic reactions to sesame seeds that were diagnosed at the Allergy Unit, Department of Dermatology, Zurich, Switzerland between 1978 and 1991. In 1991 alone, we registered three cases of anaphylactic reaction to falafel vegetable burgers in patients allergic to sesame seeds. A falafel is an oriental specialty consisting of a wheat flour bun filled with chickpea balls. It is served together with a white sauce containing freshly ground sesame seeds. Our cases highlight the potential danger of vegetarian food and underline the importance of a proper allergologic assessment to recognize food allergy promptly so that the patient can eliminate the causative allergen and use suitable medication in the event of a dietary indiscretion. PMID- 8346865 TI - Effect of economic status on the use of house dust mite avoidance measures in asthmatic children. AB - To assess the effect of socioeconomic status on compliance with house dust mite avoidance measures, we interviewed the parents of 60 mite-allergic, asthmatic children about mite avoidance. Thirty were of lower socioeconomic status and 30 were of higher socioeconomic status, as determined by the type of insurance. All had previously learned mite avoidance measures at the time of diagnosis. Twenty of 30 lower socioeconomic status parents had removed stuffed toys from the child's bedroom compared with only 12 of 30 higher socioeconomic status parents (P = .07). Twelve of 30 parents in the lower socioeconomic status group had obtained plastic mattress covers compared with 22 of the 30 higher socioeconomic status parents (P = .018). Eighteen parents in the lower socioeconomic status group expressed reasons for not obtaining plastic covers. Nine cited lack of funds, four did not know where to buy them, and four did not think it would help. Of the eight parents in the higher socioeconomic status group that did not obtain covers, six cited inconvenience and two thought it would not help. We conclude that education alone will not ensure compliance with house dust mite controls. Economic factors influence utilization. Access to free or low cost mite-proof pillow and mattress covers may improve asthma care for poor children. PMID- 8346866 TI - Heterogeneity of human Fc epsilon RI-bearing cells. AB - Basophils and mast cells (Fc epsilon RI-bearing cells) play important but clearly distinct roles in human inflammatory and allergic reactions. While many similarities have been described, it is increasingly evident that many more differences exist between these two cell types. These include maturational and ultrastructural as well as functional differences. Basophils and mast cells can be activated by different stimuli, produce different profiles of inflammatory mediators, and their response can be modulated in a different fashion. The heterogeneity of Fc epsilon RI-bearing cells has recently been extended by studies on mast cells isolated from different human tissues. These studies may suggest the existence of different human mast cell phenotypes the development of which may be regulated by microenvironmental factors. A better understanding of the heterogeneity of basophils and mast cells is a necessary step to define their respective roles in the pathophysiology of human inflammatory responses. PMID- 8346868 TI - Influence of hypoallergenic milk formula on the incidence of early allergic manifestations in infants predisposed to atopic diseases. AB - One hundred twenty-two infants at risk of atopy on the basis of IgE screening at birth and family history of atopy were studied. The occurrence of atopic manifestations was analyzed in relation to their diets during the first 3 months of age. Only the infants receiving hypoallergenic milk were protected effectively; all other regimens (humanized cow milk, hypoallergenic milk or humanized cow milk + supplements) increased the frequency of allergic symptoms (P < .07). After a 1-year follow-up, the infants fed strictly on hypoallergenic milk during their 3 first months presented allergic symptoms less frequently than other infants (P < .007). PMID- 8346867 TI - Time course of plasma histamine and tryptase following food challenges in children with suspected food allergy. AB - This study was undertaken to investigate the kinetics of histamine and tryptase in the circulation of patients with food allergy and to determine whether the measurements of plasma histamine and tryptase concentrations after food challenges provided additional predictive markers for the diagnosis and evaluation of food allergy. Twenty-one open food challenges were performed on 13 patients with suspected food allergy. Plasma histamine and tryptase concentrations were measured during 4 hours after challenge. In the group of patients with immediate reactions after challenges, the mean plasma histamine concentration rose significantly at 120 and 240 minutes after the challenge, and the mean plasma tryptase concentration was increased significantly at 240 minutes after challenge. Plasma histamine and tryptase concentrations were measured during 24 hours after 8 open food challenges in 7 other patients with suspected food allergy. In each patient with a nonimmediate reaction, plasma histamine concentrations were increased at the onset of symptoms after challenge, but no plasma tryptase concentrations increased. The elevation of plasma histamine and tryptase in patients with immediate reactions following food challenge indicates mast cell activation. On the other hand, the elevation of plasma histamine without elevated plasma tryptase in the patients with nonimmediate reactions following food challenge may indicate basophil activation rather than mast cell activation. Plasma histamine and tryptase measurements after food challenge may be useful in the detection and evaluation of food allergy. PMID- 8346869 TI - IgG and IgE antibody responses to dust mite allergens among children with asthma in Brazil. AB - We compared exposure and levels of IgE and IgG antibodies to inhalant allergens in 20 children with asthma and positive skin tests to Dermatophagoides pteronyssinus, living in Sao Paulo, to 20 control children without history of asthma or allergy and negative skin tests to D. pteronyssinus, D. farinae, and Blomia tropicalis. In 16/20 and 17/20 houses of asthmatic and control children, respectively, at least one sample was obtained which contained > 10 micrograms Der p I/g of dust. Serum IgE antibodies to D. pteronyssinus and Blomia tropicalis were > 200 RAST U/mL in 19/20 and in 16/20 asthmatic children, respectively. In the control group, IgE antibodies to either mite species were < 40 RAST U/mL in most cases. IgG anti-Der p I and anti-Der f I antibodies were detected in 17/20 asthmatics, as opposed to 3/20 controls. Neither cat nor cockroach allergens caused significant sensitization among asthmatic or control children. Although exposure to high levels of mite allergens was common in Sao Paulo, significant IgE and IgG antibody responses were detected only in children with asthma. PMID- 8346870 TI - Fish allergy in children. AB - Fish allergy is a relevant clinical problem in fish eating and/or processing communities but, because of the technologic advances of the preserved food industry, it may now be said to be a worldwide problem. Among 558 consecutive children referred for atopic diseases, 25 (4.48%) subjects skin test- and RAST- positive to cod were recorded and we extrapolated that about 4-5/1000 children have allergy to cod in our areas. As a group, children with cod allergy seem to manifest a higher atopic condition and more severe clinical manifestations. IgE level z-score (mean +/- SD) was significantly (P < .001) higher in 68 cod positive children (14.27 +/- 3.87) than in 533 children positive to other inhalant and/or food allergens (8.12 +/- 4.06). In spite of a smaller median age (59 months), cod-positive children had a higher frequency of asthma (41/68 = 60.2%) than children with other allergies, and age at the onset of asthma was significantly (P < .001) younger in the former (32 months) than in the latter (41 months) subjects. In addition, urticaria-angioedema was more frequently recorded in cod-allergic children (23/68 = 33.8%) than in patients with allergy to inhalants (26/410 = 6.3%; P < .01), inhalants and foods different from cod (11/74 = 14.8%; P < .01), or foods different from cod (6/49 = 12.2%; P < .01). The male:female ratio in cod-allergic children (3.53) was significantly higher than that observed in children with allergy to inhalants (1.78; P = .037) or foods (0.68; P < .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346871 TI - Methyldopa hypersensitivity syndrome. AB - A 74-year-old man developed an extensive erythematous skin eruption, fever, lymphadenopathy and eosinophilia probably due to methyldopa. The symptoms reappeared shortly after unintentional reexposure to the drug. The positive results of two in vitro tests for the detection of drug allergy not only give further support to the causal relationship between the drug and the symptoms, but also indicate the involvement of an immunologic, allergic mechanism. Although every individual symptom represented in our case has been reported in previous cases, the association of the symptoms together in one patient has never before been reported. An awareness that adverse reactions to methyldopa can mimic a variety of acute infectious diseases and lymphoproliferative disorders is the key to diagnosis and might prevent unnecessary hospitalizations, procedures, and use of potentially toxic antibiotics and chemotherapy. PMID- 8346872 TI - Practical issues in asthma management: correct use of inhalation devices. PMID- 8346873 TI - The need for early interventions in childhood asthma. PMID- 8346874 TI - A comprehensive evaluation of within- and between-worker components of occupational exposure to chemical agents. AB - A database of approximately 20,000 chemical exposures has been constructed in close co-operation between the School of Public Health of the University of North Carolina at Chapel Hill and the Department of Air Pollution of the Wageningen Agricultural University. A special feature of this database is that only multiple measurements of exposure from the same workers were included. This enabled estimation of within- and between-worker variance components of occupational exposure to chemical agents throughout industry. Most of the groups were not uniformly exposed as is generally assumed by occupational hygienists. In fact only 42 out of a total of 165 groups (25%), based on job title and factory, had 95% of individual mean exposures within a two-fold range. On the contrary, about 30% of the groups had 95% of individual mean exposures in a range which was greater than 10-fold. Environmental and production factors were shown to have distinct influences on the within-worker (day-to-day) variability, but not on the between-worker variability. Groups working outdoors and those working without local exhaust ventilation showed more day-to-day variability than groups working indoors and those working with local exhaust ventilation. Groups consisting of mobile workers, those working with an intermittent process and those where the source of contamination was either local or mobile also showed great day-to-day variability. In a multivariate regression model, environment (indoors-outdoors) and type of process (continuous-intermittent) explained 41% of the variability in the within-worker component of variance. Another model, in which only type of process (continuous-intermittent) had a significant effect, explained only 13% of the variability in the between-worker component of variance. PMID- 8346875 TI - Dust from cotton manufacture: changing from static to personal sampling. AB - Several designs of personal samplers were tested for use to collect cotton dust. The IOM personal inhalable-dust sampler was selected because: (1) collection of the whole inhalable fraction was preferred, since all inhaled sizes are under suspicion as contributing to respiratory symptoms in cotton exposure; (2) this sampler is well characterized; and (3) it was found to be practicable in the environments examined. Gauze shields to exclude 'fly' from the personal sampler were tried, but were rejected mainly because measurement of the whole inhalable fraction by a validated sampler was felt to be more appropriate. A range of processes at a representative selection of mills was assessed by a hygiene team, and classified as 'clean' or 'dirty' in terms of present standards of control. This classification agreed well with subsequent measurements using the present method, which uses a large static sampler. A personal sampling survey then showed that in about two-thirds of 'clean' processes personal exposure of at least 80% of those employed was less than about 2-2.5 mg m-3. Only one-tenth of 'dirty' processes met this standard. Personal exposure correlates poorly with the present static method, as expected, but comparison of the results suggested that a mean background level of 0.5 mg m-3 would correspond to a median personal exposure of about 2.2 mg m-3. Side-by-side measurements by the background method differed by less than 0.15 mg m-3 on about 95% of occasions. Niven et al. (to be published) have compared the IOM head used in this study with the Manchester University sampler previously used by Cinkotai et al. [Ann. occup. Hyg. 32, 103-113 (1988)] to derive a relationship between personal exposure and prevalence of byssinotic symptoms in spinners. According to Cinkotai et al.'s results the concentrations of 2-2.5 mg m-3 discussed would correspond to a prevalence of 3-5%. However, this prevalence probably reflects higher exposures in the past. PMID- 8346876 TI - Occupational health problems in processing of X-ray photographic films. AB - Hazards to health from exposure to chemicals in automatic processing of photographic film is well documented by ILO and others. In the early 1980s increasing reports of miscellaneous health problems including respiratory and skin effects in radiographers processing X-ray films were published. In some cases asthmatic type responses were reported to be so severe as to exclude the radiographer from further work. It has been suggested that the increased number of such cases coincided with process changes, in particular the increased addition of glutaraldehyde as a hardening agent in the developer to offset the softening of the film especially those of low silver content. Attention must also be focused however on other miscellaneous chemicals present and of the possibility of synergistic reactions. The major problems appear to be associated with heavy workloads, poorly designed and ill-ventilated darkrooms or processing rooms, and lack of appropriate safe handling techniques for the chemicals used. Several studies illustrate improvements by attention to good occupational hygiene practice. The necessity for a holistic approach to control of such a complex micro-environment is stressed. It is unlikely that a single causal agent can be identified. PMID- 8346877 TI - Asbestos induced oxidative injury to DNA. AB - DNA-damaging effects of asbestos in the presence of organic peroxides and hydroperoxides were investigated. The destabilization of the secondary structure of DNA, damage to deoxyribose sugar and DNA fidelity were measured, respectively, by S-1 nuclease hydrolysis, the formation of thiobarbituric acid (TBA)-reacting species and a melting temperature (Tm) profile using calf thymus DNA. S-1 nuclease hydrolysis and Tm determinations have shown that the presence of benzoylperoxide (BOOB), cumene hydroperoxide (COOH) or tertiary-butyl hydroperoxide (t-BOOH) increased asbestos-mediated DNA damage by a large factor compared either to asbestos alone or to peroxide or hydroperoxide alone. However, no formation of TBA-reacting species could be observed in this system. The quenchers of reactive oxygen species (ROS) afforded protection against DNA damage. These results suggest that asbestos in the presence of organic peroxides and hydroperoxides damage the DNA which is mediated by the generation of oxygen free radicals. The significance of these results in relation to the development of cancer of the respiratory tract among the asbestos exposed population is discussed. PMID- 8346878 TI - Education and training in occupational hygiene in the United Kingdom. AB - Occupational hygiene education and training is undergoing rapid changes both in the United Kingdom and elsewhere, developing closer links with safety and environmental matters whilst retaining the essential and well developed links with occupational medicine. At the same time major developments in the role of professional accreditation bodies including BEBOH are being reviewed. This paper identifies recurring themes on the scope of professionalism, accreditation and the requisite education and training for occupational hygienists. PMID- 8346879 TI - [Striated osteopathy]. AB - Striated osteopathy, a roentgenological entity characterized by longitudinal striations, can occur concomitantly with a number of disorders which should be routinely looked for. There are three types of striated osteopathy. The pure form without severe bone disorders is the form originally reported by Voorhoeve. In the second form, there is a concomitant fibrous dysplasia, such as Jaffe Lichtenstein-Uehlinger disease, Ollier enchondromatosis, sponastrism dysplasia, or osteopetrosis. This group also includes bone dysplasias with sclerosis such as melorheostosis, osteopecilia, and sclerosis of the base of the skull which is sometimes seen in patients with striated osteopathy. In the third form, striated osteopathy occurs concomitantly with a skin disease such as patchy dermal hypoplasia or hyperpigmented skin lesions. PMID- 8346882 TI - [Psychological approach to obesity in children and adolescents in a multidisciplinary consultation]. AB - Obesity is a multifactorial syndrome involving both a genetic susceptibility and environmental factors such as early eating experiences in infancy. Interviews, drawings, and a personality test (Rorschach) were used to classify obese children according to their personality. Results suggest that the eating disorder is only one component of a more global alteration in psychological organization. These data support the need for psychological intervention. PMID- 8346880 TI - [Energy metabolism in obese children]. AB - Childhood obesity results from excessive dietary intake as compared with energy expenditure. This imbalance can result from either overeating or a constitutional decrease in one or several of the components of energy expenditure: resting metabolic rate, diet-induced thermogenesis, or exercise-related thermogenesis. Decreased energy expenditure is probably at least partly genetic in origin, contributing to the significant clustering of obesity in families. Management aims at reducing the imbalance by decreasing the caloric intake. Once the desired weight is achieved, intake must be adjusted to expenditure to avoid weight regain. PMID- 8346881 TI - [Obesity in children: value of clinical evaluation criteria]. AB - To clarify risk factors for obesity in children and look for factors affecting prognosis, simple clinical parameters were analyzed in 113 obese children at the first visit and during treatment. Height and weight charts were constructed. The main risk factors were parental obesity, excess weight at the age of one and above all young age at the time of the rebound in body mass index (W/H2). Severity of obesity was unrelated to spontaneous caloric intake but was negatively correlated with age at the time of rebound in body mass index (r = 0.34; p = 0.017) and above all with age at onset of obesity (r = -0.53; p < 0.001). Closely spaced measurements of weight, stature, and body mass index in high risk children would allow appropriate preventive treatment before the phase of established obesity. Curative treatment is disappointing: only 28% of the study subjects achieved significant reductions in weight. PMID- 8346883 TI - [Deficiency in medium chain acyl coA dehydrogenase manifested as febrile coma]. AB - A 21-month-old infant developed coma with hypotonia during a viral infection. Acyl CoA dehydrogenase deficiency was diagnosed on the basis of results of the chromatographic study of organic acids performed on a urine specimen collected during the acute episode. However, other disorders of mitochondrial and fatty acid oxygenation can generate similar symptoms. Emphasis is put on the need for collecting urine specimens in patients who develop alterations in consciousness and hypoglycemia without ketonuria during prolonged fasting or repeated vomiting due to a viral infection. Urine chromatography can suggest which enzyme is defective, although the diagnosis should always be confirmed by a study of fatty acid oxygenation in lymphocytes or fibroblasts. PMID- 8346884 TI - [Histiocytosis X and sclerosing cholangitis]. AB - The case of a seven-year-old with multifocal (type II) Langheran's cell histiocytosis since the age of two years is reported. Despite therapy, biliary cirrhosis with portal hypertension developed gradually. Histologic studies of liver biopsy specimens, computed tomography, and transhepatic cholangiography disclosed dilatation of the bile ducts, suggesting sclerosing cholangitis, a specific complication of Langherans' cell histiocytosis which precipitates the development of biliary cirrhosis. PMID- 8346885 TI - [Neural sarcoidosis in children. A case report]. AB - A case of cerebral sarcoidosis of fortuitous discovery is reported in an adolescent. Neurosarcoidosis is exceedingly rare in the pediatric age groups. Clinical manifestations are widely variable and nonspecific, making diagnosis difficult in patients without extraneurologic involvement. The mainstay of management is early, prolonged corticosteroid therapy. Outcome varies with location of the lesions. PMID- 8346886 TI - [Type II primordial microcephalic dwarfism. Report of a patient with completed growth]. AB - Type II primordial microcephalic dwarfism is a rare form of bird-headed dwarfism individualized in 1982 by Majewski. A case in a female patent with completed growth illustrates the main features, which include severe growth retardation (greater than 4 SD reduction in height) of prenatal onset, short limbs, coxa vara with epiphysiolysis of the hips, metaphyseal flaring and, in some instances, shortness of the ulnas and curvature of the radiuses. A genetic cause (with autosomal recessive inheritance) is very likely. A number of features in the case reported herein may be of pathogenetic relevance: growth hormone levels were elevated before closure of the epiphyses and normal thereafter, no growth spurt occurred at puberty, polycystic ovaries with hirsutism developed after puberty, and surgical wound healing was unusually slow. PMID- 8346887 TI - [Pulmonary sequestration in an infant]. AB - A case of intralobar pulmonary sequestration in an infant is reported. The lesion presented as recurrent bronchopulmonary infections. The chest film showed a density in the right lower lobe, in which air-filled images and air-fluid levels developed rapidly. Aortography demonstrated systemic blood supply to the lesion from three arteries stemming from the thoracic aorta. The pathological study of the operative specimen confirmed the diagnosis. Postoperative outcome was satisfactory. PMID- 8346888 TI - [Measuring fecal lipid output in infants receiving a neonatal milk-based formula]. AB - Fecal fat output was measured over three days in ten infants aged 28 to 115 days fed an infant formula (SMA Comfort, Sodilac) containing 39.2% unsaturated fatty acids and 20.1% medium-chain triglycerides (C8, C10, and C12). Fat intake ranged from 59.32 to 136.80 g. Mean fat absorption coefficient was 96 +/- 2%. SMA Comfort offers a fat absorption coefficient comparable to that seen with breast milk. PMID- 8346889 TI - A practical approach to surgical training abroad. PMID- 8346890 TI - An audit of the surgical workload on a renal unit. AB - OBJECTIVE: To assess the surgical workload on a renal unit, with particular reference to non-transplant-related surgery and to assess the workload in relation to surgical staffing levels. DESIGN: Prospective audit of all surgical procedures carried out on patients in acute or chronic renal failure, and on transplanted patients, within a one year period. SETTING: A purpose-built renal unit serving a population of 1.7 million. MAIN OUTCOME MEASURES: The number of surgical procedures, both transplant and non-transplant-related, according to type and severity, with particular reference to the levels of surgical staffing. RESULTS: Transplant-related surgery accounted for only 6.5 per cent of the total surgical workload (general, vascular and renal) of the 'transplant surgeons'. Taking into account only the renal-related workload, transplant-related surgery accounted for just 16.5 per cent of the workload, the remainder being related to vascular access and peritoneal access for dialysis, and general surgical procedures on patients in renal failure and transplanted patients. The surgical workload undertaken by a relatively small number of staff was high, representing 531 Intermediate Equivalents per Service Equivalent Value per annum. CONCLUSIONS: When assessing workload and adequacy of surgical staffing on a Renal Unit, care should be taken to account for all surgical activity on renal patients and not just that related to transplantation since only 16.5 per cent of the surgical workload is transplant-related. PMID- 8346891 TI - What value is the patient's experience of surgery to surgeons?: the merits and demerits of patient satisfaction surveys. PMID- 8346892 TI - Portraits of a paradox: council room reflections. PMID- 8346894 TI - A test of a path model of biocultural transmission of fertility. AB - A model adapted to a general linear model of phenotypic transmission (two components: (1) genetic additive, (2) cultural [age at marriage]) has been used to analyse the familial correlations of fertility (number of children) born before the demographic transition at Arthez d'Asson (Bearn, 1744-1889). The model is rejected: chi 2 = 55.7 with 6d.f. In the ancient demographical regime, reproduction and nuptiality of a couple were not influenced by their parents but by their generation. PMID- 8346893 TI - Individual and community characteristics influencing breastfeeding duration in Vietnam. AB - This analysis of selected community and maternal characteristics influencing duration of breastfeeding in Vietnam utilized data from the 1988 Demographic and Health Survey and 1990 Accessibility of Contraceptives Survey available for the 4434 children born to 2769 women having their last birth between 1983-88. Explanatory variables included as covariates in the hazards model were mother's education, age of the mother at the time of the child's birth, birth order, and gender of the child, urban versus rural residence, infant mortality risk in the child's province, locality (mountains and highlands compared to delta and coastal), and region of the country (north, south). Indicators of development in the child's village included availability of electricity and public transportation. Breastfeeding duration was longer among the more highly educated women and among those women living in provinces with higher infant mortality. However, there were no significant differences in the duration of breastfeeding with variations among certain development characteristics of the village. Although there were regional differences in the duration of breastfeeding for the rural population, there were no regional differences for the overall population. There were no significant variations in the duration of breastfeeding by age of the mother, birth order or gender of the child. Although there were significant variations in duration of breastfeeding by some maternal and community characteristics, between 80-90 per cent of all women breastfeed for at least the first year of the child's life. PMID- 8346896 TI - Estimating inbreeding from the Faculty Office Registers, 1534-1540. AB - Estimates of inbreeding are rather scarce for British populations. A number of studies, especially of Scottish island populations, have focused on pedigree analysis, whilst others have used survey methods or inference from isonymy. By comparison with continental Europe, however, little is known of the historical development of inbreeding. This is undoubtedly due to the lack of evidence from dispensations to marry blood relatives, which are routinely available in the records of marriage of the Roman Catholic church. The paper uses as its data source the Faculty Office Registers, 1534-1540, which were the product of a new system of issuing dispensations following the Dispensations Act of 1533, and which are among the earliest administrative records of the Church of England, founded as a result of Henry VIII's breach with Rome. Dispensations are recorded in the Faculty Office until 1540, when all prohibitions on marriage beyond the proscribed relationships laid down in Leviticus were lifted. The data suggest surprisingly low levels of consanguineous marriage, including a lack of first cousin marriages. These findings are discussed in terms of the reliability of the archive, and of the social and religious views attending marriage between blood relatives in the medieval and early modern periods. PMID- 8346895 TI - Evidence for a secular trend in heights and weights of adults in Papua New Guinea. AB - Evidence for a secular change in heights and weights of adults of 13 populations in Papua New Guinea was sought by comparing data collected at two different times, using three types of source. These are: (1) values obtained from the literature; (2) previously unpublished measurements made by author; and (3) data found in the research notes of A.C. Haddon, and which were collected between 1897 and 1914. An increase in heights and weights has taken place in some, but not all, populations examined, whilst a decrease in adult body size has taken place in a smaller number of groups. PMID- 8346897 TI - Respiratory conditions, including asthma, and height in primary school. AB - The National Study of Health and Growth (NSHG) of primary school children has examined the relationships between height and each of six separate respiratory conditions, one of which was asthma, in children aged 5-11 years, allowing for a number of genetic and environmental confounding factors, in particular for parental height. The relationships were investigated in a 'representative' sample of 4974 Caucasian English children in 1984 and in an 'ethnic/inner city' sample of 3419 Afro-Caribbean/Indian and Pakistani/Caucasian English children in 1985. None of the respiratory conditions was found to be related to height except for 'wheeze most days', whether or not it was accompanied by an asthma attack in the last 12 months. The Caucasian children in the 'representative' sample who had 'wheeze most days', were 0.17 height standard deviation score (95% confidence interval 0.03 to 0.31) less (approximately 1 cm) than those with no wheeze. Comparisons with previous results for NSHG 'representative' Caucasian English children in 1973 showed good agreement except for children with three or more asthma attacks who were found to be shorter in 1973, but not in 1984, which may reflect improved treatment, or milder asthma being reported in 1984. It was concluded that, in the 1980s, the respiratory conditions were not related to height. The exception was 'wheeze most days'. It is suggested that this is an indicator of sickness, most likely asthma, which is being experienced with sufficient severity to affect growth slightly. PMID- 8346898 TI - A path analysis of some determinants of infant growth in Khartoum. AB - The interrelationships between some socioeconomic and behavioural characteristics of mothers and the growth and illness experience of their infants in poor Khartoum townships have been examined by path analysis. For both infant body weight and supine length it is shown that weaning age and illness experience are important determinants of growth. It is also shown that greater maternal income has disadvantageous effects through encouraging early weaning. Most importantly the infants of housewives have later weaning, less illness and greater weight and length at 1 year of age than the infants of mothers with jobs, showing the value of time for caring in the prevailing environmental circumstances. PMID- 8346899 TI - Inbreeding and developmental stability in a small human population. AB - Inbreeding coefficients are reported for all members of the isolated Havasupai tribe of northern Arizona (USA), based upon pedigrees which are as deep as eight generations. Because inbreeding has been repeatedly shown to reduce developmental homeostasis in a large number of species, we ask if the degree of inbreeding in the Havasupai is associated with reduced developmental stability. Fluctuating asymmetry in two dermatoglyphic traits suggests that inbreeding significantly compromises developmental homeostasis in this population. PMID- 8346900 TI - Maximal aerobic power in high-altitude runners. AB - Maximal aerobic power (VO2max) was assessed in seven male and one female middle- and long-distance recreational runners residing in La Paz, Bolivia (3600 m). All runners were born and raised at high altitudes (> 2500). Mean VO2max in the male runners was 60.8 ml/kg/min while VO2max in the female runner was 55.5 ml/kg/min. These values are higher than in any previously reported sample of either trained or untrained high-altitude natives. In addition, mean VO2max in the La Paz male runners and VO2max in the La Paz female runner were very similar to those found in comparable low-altitude samples of recreational athletes, suggesting that the cardiorespiratory systems of both normally active and highly active native Andean highlanders are capable of successfully responding to the stress of hypobaric hypoxia. This ability may have both developmental and genetic components. PMID- 8346902 TI - High-throughput microtiter plate-based chromogenic assays for glycosidase inhibitors. AB - Rapid microtiter plate-based colorimetric assays have been developed that allow the screening of large numbers of samples for the presence of inhibitors of alpha glucosidase, alpha-amylase, and beta-galactosidase. The assays are particularly useful for screening large numbers of microbial culture filtrates. PMID- 8346901 TI - Cellular and metabolic engineering. An overview. AB - Metabolic engineering is defined as the purposeful modification of intermediary metabolism using recombinant DNA techniques. Cellular engineering, a more inclusive term, is defined as the purposeful modification of cell properties using the same techniques. Examples of cellular and metabolic engineering are divided into five categories: 1. Improved production of chemicals already produced by the host organism; 2. Extended substrate range for growth and product formation; 3. Addition of new catabolic activities for degradation of toxic chemicals; 4. Production of chemicals new to the host organism; and 5. Modification of cell properties. Over 100 examples of cellular and metabolic engineering are summarized. Several molecular biological, analytical chemistry, and mathematical and computational tools of relevance to cellular and metabolic engineering are reviewed. The importance of host selection and gene selection is emphasized. Finally, some future directions and emerging areas are presented. PMID- 8346903 TI - DNA sequencing. Recent innovations and future trends. AB - Determination of the sequence of DNA is one of the most important aspects of modern molecular biology. New sequencing methods currently being developed enable DNA sequence to be determined increasingly faster and more efficiently. One of the major advances in sequencing technology is the development of automated DNA sequencers. These utilize fluorescent rather than radioactive labels. A laser beam excites the fluorescent dyes, the emitted fluorescence is collected by detectors, and the information analyzed by computer. Robotic work stations are being developed to perform template preparation and purification, and the sequencing reactions themselves. Research is currently in progress to develop the technology of mass spectrometry for DNA sequencing. Success in this endeavor would mean that the gel electrophoresis step in DNA sequencing could be eliminated. A major innovation has been the application of polymerase chain reaction (PCR) technology to DNA sequence determination, which has led to the development of linear amplification sequencing (cycle sequencing). This very powerful yet technically simple method of sequencing has many advantages over conventional techniques, and may be used in manual or automated methods. Other recent innovations proposed recently to increase speed and efficiency include multiplex sequencing. This consists of pooling a number of samples and processing them as pools. After electrophoresis, the DNA is transferred to a membrane, and sequence images of the individual samples are obtained by sequential hybridizations with specific labeled oligonucleotides. Multiplex DNA sequencing has been used in conjunction with direct blotting electrophoresis to facilitate transfer of the DNA to a membrane. Chemiluminescent detection can also be used in conjunction with multiplex DNA sequencing to visualize the image on the membrane. PMID- 8346904 TI - Methods for pulsed-field gel electrophoresis. AB - The term pulsed-field gel electrophoresis (PFGE) is used as an acronym to indicate any technique that resolves (large) DNA molecules by continuous reorientation. It bridges the resolution gap between cytogenetic methods (> 5 Mb) and DNA analysis (< 50 kb). Initially, PFGE was used to study the chromosomal content of unicellular eukaryotic organisms of interest to genetic research and population health. Later, PFGE was used to construct megabase maps of segments of the human genome. Successfull utilization of PFGE requires the availability of very high-molecular weight DNA. This article describes the modification of standard DNA protocols necessary to handle large DNA molecules, based on its encapsidation in agarose. PMID- 8346905 TI - Immobilization as a tool for the stabilization of lignin peroxidase produced by Phanerochaete chrysosporium INA-12. AB - Lignin peroxidase immobilization was achieved by covalent coupling on CNBr Sepharose 4B. Protein immobilization yield was around 80%. For veratryl alcohol oxidation, in the presence of hydrogen peroxide, both soluble and bound enzymes exhibited the same pH profile with an optimum near 2.5. Catalytic parameters (kc and Km) were seriously affected by immobilization. On the other hand, immobilization provided a noticeable stabilization of the enzyme against acidic pH and high temperatures. A 15-20 increase in the half-inactivation times at pH 2.2 and 2.7, respectively, could be observed. Bound enzyme was also much more thermostable than soluble. PMID- 8346907 TI - Salt-tolerant and thermostable alkaline protease from Bacillus subtilis NCIM no. 64. AB - The proteolytic activity produced by a Bacillus subtilis isolated from a hot spring was investigated. Maximum protease production was obtained after 38 h of fermentation. Effects of various carbon and nitrogen sources indicate the requirement of starch and bacteriological peptone to be the best inducers for maximum protease production. Requirement for phosphorus was very evident, and the protease was secreted over a wide range of pH 5-11. The partially purified enzyme was stable at 60 degrees C for 30 min. Calcium ions were effective in stabilizing the enzyme, especially at higher temperature. The enzyme was extremely salt tolerant and retained 100% activity in 5M NaCl over 96 h. The molecular weight of the purified enzymes as determined by SDS-PAGE was 28,000. The enzyme was completely inactivated by PMSF, but little affected by urea, sodium dodecyl sulfate, and sodium tripoly phosphate. PMID- 8346906 TI - Immobilization of Aspergillus niger NRC 107 Xylanase and beta-Xylosidase, and Properties of the Immobilzed Enzymes. AB - Aspergillus niger NRC 107 xylanase and beta-xylosidase were immobilized on various carriers by different methods of immobilization, including physical absorption, covalent binding, ionic binding, and entrapment. The immobilized enzymes were prepared by physical adsorption on tannin-chitosan, ionic binding onto Dowex-50W, covalent binding on chitosan beads through glutaraldehyde, and entrapment in polyacrylamide had the highest activities. In most cases, the optimum pH of the immobilized enzymes were shifted to lower than those of free enzymes. The optimum reaction temperature of immobilized xylanase was shifted from 50C to 52.5-65C, whereas that of immobilized beta-xylosidase was shifted from 45C to 50-60C. The Km values of immobilized enzymes were higher than those of native enzymes. The operational stability of the immobilized enzymes was evaluated in continuous operation in packed-bead column-type reactors. The enzymes covalently bounded to chitosan showed the highest operational stability. However, the enzymes immobilized by physical absorption or by ionic binding showed a low operational stability. The enzymes entrapped in polyacrylamide exhibited lower activity, but better operational stability. PMID- 8346908 TI - Filamentous aggregates of native titin and binding of C-protein and AMP deaminase. AB - In solutions of high ionic strength, native titin-2, a large extractable fragment of the sarcomere matrix protein titin, appears as extremely long, flexible, and slender beaded strings. We report here that in solutions of lower ionic strength near neutral pH, titin-2 assembles into higher-order aggregates with surface projections. Solid phase binding assays show that two myosin-binding proteins, C protein and AMP-deaminase, are also titin-binding proteins. Both proteins decorate titin aggregates, producing filaments of more uniform appearance. Numerical Fourier transforms of these decorated aggregates show approximately 12 nm periodicities. The interaction of titin with myosin-associated proteins such as C-protein may take part in the anchoring mechanism that prevents the stretching and extension of titin filaments in the A band. PMID- 8346909 TI - Adenine nucleotides and inhibition of protein synthesis in isolated hepatocytes incubated under different pO2 levels. AB - Hepatocytes incubated at a pO2 of 0 mm Hg (N2/CO2, 95%/5%) loose their intracellular ATP content and their ability to synthesize RNA and proteins. Protein synthesis is virtually inhibited from the beginning of the incubation, while ATP content is gradually lost, thus suggesting a primary response of the cell to the absence of O2 rather than to ATP depletion. Such an early decrease of protein synthesis (as estimated as the incorporation of [14C]Leu into cell proteins) is unlikely the result of inhibition of amino acids uptake, enhanced protein degradation, or decreased RNA synthesis. Reoxygenation of such previously hypoxic cells with O2/CO2 at 95%/5% (pO2 of 700 mm Hg), leads to the recovery of both ATP and protein synthesis, even better the hypoxic period is not longer than 30 min. In hepatocytes incubated for 30 min under a pO2 of 700, 80, or 50 mm Hg, cell survival and ADP content are almost identical. Incorporation of radiolabelled leucine is linear in cells incubated under 700 mm Hg O2, but it rather stops at a pO2 of 80 or 50 mm Hg. The time course of both ATP and GTP content behaves in a similar way: it is fairly constant at a pO2 of 700 mm Hg, but a depletion is initiated after 20 min of incubation at a pO2 of 50 or 80 mm Hg. Finally, incubation of hepatocytes either at 700 or 0 mm Hg O2, in the presence of fructose (10 mM), shows that ATP content is maintained at the same level whatever the pO2 level. AMP content is increased only in cells incubated at 0 mm Hg O2 in the absence of fructose. Incorporation of radiolabelled leucine is stopped in such hypoxic cells incubated or not in the presence of fructose. From these results it appears that the presence or the absence of O2 might represent a turn on/off signal to which hepatocytes respond immediately by important metabolic changes like the inhibition of protein synthesis. PMID- 8346910 TI - Application of quantitative structure-activity relationship modeling to the evaluation of the changes in enzymatic activity of carboxypeptidase Y upon chemical modifications. AB - A series of 18 phenacyl bromide and iodoacetamide analogues have been synthesized and used to alkylate Met-398 situated in the S'1 binding site of carboxypeptidase Y. The course of the reactions was monitored by measurements of the peptidase and esterase activities. All except four of the reagents reacted selectively, and from these preparations the modified enzymes were purified and kinetically characterized toward a methyl ester substrate and a peptide substrate with a large leaving group in the P'1 position. The Km, kcat, and kcat/Km for the hydrolysis of these substrates have been quantitatively correlated to parameters describing the properties of the modification reagents. The esterase activity depends only on the steric bulk of the para-substituents with the phenacyl modified enzymes, but on both steric and electronic factors of the N-alkyl substituents with the acetamide modified enzymes. The peptidase activity, on the other hand, is dependent on steric and electronic factors with both types of modified enzymes. PMID- 8346911 TI - Steady-state kinetic evaluation of the reverse reaction for Escherichia coli 5 enolpyruvoylshikimate-3-phosphate synthase. AB - Recently it has been found that the kinetic mechanism for Escherichia coli 5 enolpyruvoylshikimate-3-phosphate synthase (EPSPS) in the forward direction is random with synergistic binding of substrates and inhibitors (K. J. Gruys, M. C. Walker, and J. A. Sikorski, 1992, Biochemistry 31, 5534). This work, however, did not address the reverse reaction with 5-enolpyruvoylshikimate-3-phosphate (EPSP) and phosphate (Pi) as substrates where a similar question of random versus ordered addition of substrates remained. Previous transient-state kinetic results led to a proposal for an equilibrium-ordered mechanism, where binding of EPSP occurs first followed by Pi (K. S. Anderson, and K. A. Johnson, 1990, Chem. Rev. 90, 1131). Steady-state kinetic results of the reverse reaction presented here suggest that, like the forward reaction, addition of substrates occurs randomly. Initial velocity studies with EPSP and Pi show a normal intersecting pattern in the reciprocal plots, consistent with a random or steady-state-ordered mechanism, but not with equilibrium-ordered addition of substrates. Inhibition of the EPSPS reverse reaction by 5-amino-S3P or the S3P-glyphosate hybrid molecule gave the expected competitive patterns versus EPSP, but mixed noncompetitive patterns versus Pi. These results also disfavor an equilibrium-ordered model, but again are consistent with a random or steady-state-ordered mechanism. A more quantitative mechanistic analysis of the inhibition data to determine the true rather than apparent Ki values provides evidence for a random over a steady-state ordered addition of substrates. These results in combination with previous findings lead to the conclusion that the mechanism is random addition of EPSP and Pi since it is the only possible model for substrate addition that is consistent with the cumulative data from all kinetic (transient- as well as steady-state) and direct binding studies. PMID- 8346913 TI - The conserved methionines of the 1.3 S biotinyl subunit of transcarboxylase: effect of mutations on conformation and activity. AB - Transcarboxylase from Propionibacterium shermanii is a biotin-containing enzyme which catalyzes the reversible transfer of a carboxyl group from methylmalonyl CoA to pyruvate. Transcarboxylase 26 S complexes consist of a central, hexameric 12 S subunit with 6 outer, 5 S subunits attached by 12 1.3 S biotinyl subunits. Each of the subunits has been cloned and expressed in Escherichia coli in active form. We have used the cloned genes in mutagenic studies of the structure function interactions of these subunits. One particular target of our studies has been the evolutionarily conserved tetrapeptide Ala-Met-Bct-Met which surrounds the biotinyl lysine. We have investigated the properties of subunits containing leucine substitutions at each methionine (1.3 S M88L and 1.3 S M90L) by assaying their activity in the two partial reactions in which this subunit participates. Partial reaction assays demonstrate that leucine substitution at either position has a greater effect on the 12 S partial reaction than on the 5 S reaction and Met 88 is more significant catalytically than Met 90. To determine whether structural alterations in the 1.3 S mutants were responsible for the effects on activity, the conformations of these mutants were investigated. In vitro hydrolysis studies with trypsin and V8 protease demonstrated differences in the susceptibility of 1.3 S M88L relative to 1.3 S WT and 1.3 S M90L. Complexes of avidin with 1.3 S WT or mutant subunits, as monitored by fluorescence properties, indicated that the microenvironment of the biocytin of 1.3 S M88L was different from those of 1.3 S WT and 1.3 S M90L. By contrast, substrate binding (oxalacetate for 5 S and methylmalonyl-CoA for 12 S) was unaffected by any of the 1.3 S mutants. Taken together, these results indicate that the conserved tetrapeptide of the 1.3 S biotinyl subunit, particularly Met 88, is required to provide an essential conformation and proper binding properties for catalysis of the partial reactions and the overall reaction. PMID- 8346912 TI - Isolation and biochemical characterization of procathepsin E from human erythrocyte membranes. AB - Cathepsin E (CE) is an intracellular, nonlysosomal aspartic proteinase which consists of two identical subunits with a molecular weight of about 42 kDa (K. Yamamoto, M. Takeda, H. Yamamoto, M. Tatsumi, and Y. Kato, 1985, J. Biochem. 97, 821-830). In order to clarify its nature and proteolytic activation, the pro-CE and the mature enzyme were simultaneously purified from human erythrocyte membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the reduced proenzyme showed a single protein band, exhibiting an apparent molecular weight of 46 kDa. The proenzyme was found to be catalytically inactive, but it was rapidly converted into the active enzyme after brief acid treatment at pH 4.0, which was accompanied by a reduction in molecular size to 43 kDa. The activated form of pro-CE was essentially identical with the mature enzyme in enzymatic properties such as specific activities toward synthetic and protein substrates, and susceptibilities to various protease inhibitors. The N-terminal amino acid sequence analysis revealed that pro-CE started with the third amino acid residue, Ser3, of the sequence of human gastric CE predicted from its cDNA sequence and that the autocatalytic cleavage occurred at the Met36-Ile37 and Phe39-Thr40 bonds to produce two mature isozymic forms. The mature enzyme purified from human erythrocyte membranes also showed two different N-terminal sequences identical with those of the in vitro-activated form of pro-CE. The proenzyme, as well as the mature enzyme from human and rat erythrocyte membranes, was shown to be as an endo-beta-N-acetylglucosaminidase H-resistant form, whereas CE from rat spleen was N-glycosylated with a high-mannose-type oligosaccharide chain, suggesting that the carbohydrate modification of this protein varies with the cell type or the cellular localization. These data also suggest that the proenzyme in human erythrocytes is processed from the high-mannose type to the complex/hybrid type during its biosynthesis at early stages of erythroid differentiation, which precedes the proteolytic activation. PMID- 8346915 TI - Two purine biosynthetic enzymes that are required for cadmium tolerance in Schizosaccharomyces pombe utilize cysteine sulfinate in vitro. AB - In plants and in certain fungi, exposure to heavy metals induces the synthesis of metal-binding peptides commonly known as phytochelatins. With cadmium, phytochelatins can sequester the metal into a sulfide-containing complex. From genetic analysis of fission yeast mutants, we previously reported that two genes in purine biosynthesis, encoding adenylosuccinate synthetase and succinoaminoimidazole carboxamide ribonucleotide (SAICAR) synthetase, are required for the biogenesis of the phytochelatin-cadmium-sulfide complex in vivo. We suggested that a sulfur analog of aspartate, cysteine sulfinate, might be utilized by these enzymes and that the cysteine sulfinate-derived products would then become intermediates or carriers in a sulfur transfer pathway leading to the sulfide found within the metal chelate. In this paper, we report that partially purified adenylosuccinate synthetase and SAICAR synthetase are capable of utilizing cysteine sulfinate in vitro to form sulfur analog products. Adenylosuccinate lyase, however, fails to catalyze further conversion of these sulfur derivatives. These observations support the genetic data implicating a link among purine biosynthetic enzymes, sulfur metabolism, and cadmium tolerance. PMID- 8346914 TI - Alanine dehydrogenase from soybean nodule bacteroids: purification and properties. AB - Alanine dehydrogenase (ALADH) from soybean nodule bacteriods was purified 184 fold with 14% yield, using ammonium sulfate precipitation, hydroxylapatite, gel filtration, ion exchange, and dye affinity chromatography. The subunit molecular weight was 43,000 and the native molecular weight was approximately 190,000, suggesting that ALADH is a tetramer. ALADH was confined to the bacteroid cytosol fraction only. ALADH is specific for NAD(H) and does not use NADP(H) as a substrate, but it does use glyoxylate and hydroxypyruvate as substrates in lieu of pyruvate. The pH optimum was 8.5 for the amination reaction and 10.0 for the deamination reaction. The apparent Michaelis constants for NADH, NH4+, pyruvate, L-alanine, and NAD were 86 microM, 8.9 mM, 0.49 mM, 1 mM and 200 microM, respectively. High concentrations of pyruvate, L-alanine, or NH4+ caused inhibition of activity with Ki's of 8.6 mM, 6.5-15 mM, and 188 mM, respectively. The amination reaction of ALADH was 95-100% of the control at levels of NADH/NAD corresponding to those measured in isolated bacteroids. The deamination reaction, on the other hand, was only 35-40% of control. Thus, an aminating role for ALADH is possible. PMID- 8346916 TI - The signal for retention of the egasyn-glucuronidase complex within the endoplasmic reticulum. AB - Egasyn is localized within the lumen of the endoplasmic reticulum (ER) where it complexes with and thus causes sequestration of a considerable portion of beta glucuronidase. Egasyn has an HTEL sequence at its carboxyl terminus rather than the KDEL sequence that serves as a retention signal for many ER lumenal proteins. To determine whether the HTEL sequence acts as an ER retention signal and/or functions in complex formation, HTEL-deleted egasyn was expressed in mammalian cell lines. The majority of HTEL-deleted egasyn was secreted, while wild type egasyn was retained in the ER. Furthermore, the egasyn HTEL sequence, when added to the carboxyl termini of two secretory proteins, mouse esterase, Es-N, and rat alpha 1-acid glycoprotein (AGP), caused retention of both proteins within the ER, demonstrating that the HTEL sequence is both necessary and sufficient for retention of egasyn and, by extension, the egasyn-glucuronidase complex within the ER. Other carboxyl terminal tetrapeptides including HIEL and HVEL, naturally occurring in other ER lumenal proteins, were also sufficient for ER retention of AGP, while HTEHT and HTEHK were inefficient in ER retention. The HTEL sequence, in contrast, is not required for egasyn-glucuronidase complex formation. Further, the complex is apparently unstable outside the ER since it was not visible in the medium of cells transfected with egasyn lacking the HTEL sequence despite abundant secretion of this egasyn. These results show that it is possible to localize proteins within the lumen of the ER if they form complexes with ER lumenal proteins containing an intrinsic ER retention sequence. PMID- 8346917 TI - Overexpression in Escherichia coli of soluble aristolochene synthase from Penicillium roqueforti. AB - Aristolochene synthase, a fungal cyclase which has been isolated from Aspergillus terreus and Penicillium roqueforti, catalyzes the cyclization of farnesyl diphosphate to the sesquiterpene hydrocarbon aristolochene. The aristolochene synthase gene (Ari1) of P. roqueforti has previously been cloned and expressed at low levels as a protein A-aristolochene synthase fusion protein in Escherichia coli. We have now used the polymerase chain reaction to amplify the aristolochene synthase coding sequence using engineered primers which produced dsDNA carrying an EcoRI restriction site and the T7 gene 10 ribosome binding site and translational spacer element immediately upstream of the ATG start codon and a BamHI site adjacent to the TAA stop codon. The PCR product was digested with EcoRI and BamHI and inserted into the multiple cloning site of the expression vector pLM1 which carried the promoter and translational leader sequence from T7 gene 10 and the E. coli rrnBT1T2 tandem transcription terminator. Cloning of the resulting construct into E. coli XL1-Blue and subcloning into the expression host E. coli BL21 (DE3) gave transformants which expressed aristolochene synthase at levels up to 40% of soluble protein when induced with isopropyl beta-D thiogalactoside. Purification of the recombinant protein by ammonium sulfate precipitation, ion-exchange chromatography on Q Sepharose, and affinity dye chromatography on Reactive Blue 4-agarose gave homogenous aristolochene synthase which had the expected N-terminal sequence, ATSTE, mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and steady-state kinetic parameters when compared to native fungal protein. PMID- 8346918 TI - The effect of changes in iron redox state on the activity of enzymes sensitive to modification of SH groups. AB - Iron ions in micromolar concentrations induced a rapid and selective inhibition of the activity of skeletal muscle creatine kinase (CK), sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and pyruvate kinase (PK). This effect of iron was dependent on the presence of adenine nucleotides and on the redox state of iron. Changing the redox state of the media created different Fe2+/Fe3+ ratios which selectively depressed different enzymes: depression of PK activity occurred when iron was predominantly in its reduced form and, consequently, when there was a high Fe2+/Fe3+ ratio; depression of SR Ca2+ uptake and SR Ca(2+)-ATPase activity occurred when the Fe2+/Fe3+ ratio was close to 1; depression of CK activity occurred when iron was predominantly in its oxidized form and the Fe2+/Fe3+ ratio was low. All iron-sensitive enzymes possessed sulfhydryl groups, accessible to N ethylmaleimide (NEM), which were essential for their activity. The rate of inhibition of enzyme activity with NEM increased in the order PK < Ca(2+)-ATPase < CK. Iron-induced depression of CK and PK activities was reversible by dithiotreithol. Results suggest that changes in the redox state of cellular microenvironments, which inevitably occur during reperfusion of ischemic tissue or rapid increase in tissue oxygen consumption, may selectively depress the activity of several enzymes bearing SH groups that are sensitive to modifications and that are essential for their activity. Iron-induced depression of enzyme activity depends on the availability of iron bound to adenine nucleotides and possibly to other low molecular weight chelators and on the Fe2+/Fe3+ ratio generated by the induced redox change. PMID- 8346919 TI - The kinetics of multiphosphorylation of rhodopsin. AB - Rhodopsin kinase catalyzes the incorporation of up to seven phosphates into the carboxyl terminal region of freshly bleached rhodopsin. In order to study the mechanism of this reaction, we have separated different phosphorylated species of rhodopsin using Mono P FPLC chromatofocusing chromatography. The purity of the isolated species of rhodopsin was determined by isoelectric focusing. Separation yielded two forms of monophosphorylated and two diphosphorylated species of rhodopsin. Other species, containing up to five phosphates, were not fully separated. The phosphorylated forms of rhodopsin were characterized by competition enzyme-linked immunosorbent assay and immunoblotting using anti rhodopsin site-specific monoclonal antibodies. A combination of the above methods allowed quantitative determination of the formation of different phosphorylated species of rhodopsin. A computer model for the consecutive time course of rhodopsin phosphorylation was developed and employed to characterize this reaction. Our data suggest that the rate of incorporation of the first phosphates into rhodopsin is slower than the rate of formation of more highly phosphorylated species. These data are supported by results showing that some monophosphorylated synthetic peptides are phosphorylated significantly faster than control unphosphorylated peptides. PMID- 8346920 TI - Cloning, sequencing, and functional studies of phenobarbital-inducible forms of cytochrome P450 2B and 4B expressed in rabbit kidney. AB - Expression of several forms of cytochrome P450 2B and of P450 4B1 in rabbit kidney was investigated by cloning from cDNA libraries constructed with renal mRNA from animals treated with phenobarbital. Isolation and sequencing of several cDNAs demonstrated that: (i) cytochrome P450 2B-B0 can be found in rabbit kidney along with a newly discovered form of P450 2B termed "P450 2B-Bx." P450 2B-Bx differs from P450 2B-B0 at 25 nucleotide positions and at four positions in the derived sequence of 491 amino acids. Two previously identified forms of cytochrome P450 2B, 2B-B1 and 2B-B2, are not detected in rabbit kidney. cDNA encoding cytochrome P450 4B1 was also cloned from the kidney library and found to be identical in sequence to cDNAs cloned from rabbit hepatic and pulmonary libraries. Analysis of renal mRNA indicates that forms of cytochrome P450 2B and P450 4B1 are expressed in a number of species but induced by phenobarbital in rabbit only (4B1) or rabbit and hamster (2B). Relatively high levels of mRNA related to P450 4B1 were detected in samples from untreated and phenobarbital treated mice. Analysis of protein by immunoblotting was less sensitive but produced results consistent with those obtained by analysis of mRNA; protein related to cytochrome P450 2B was detected in renal microsomal samples from rabbit and hamster (phenobarbital > untreated), and protein related to P450 4B1 in samples from rabbits (phenobarbital > untreated) and mice (phenobarbital = untreated). The four forms of cytochrome P450 2B were expressed in COS-7 cells, and their activities were evaluated with androstenedione, testosterone, and 7 ethoxycoumarin as substrates. Three of the P450 2B forms, B0, B1, and Bx, metabolize these substrates in a manner characterized by preference for 16 beta hydroxylation of androstenedione, low testosterone 16-hydroxylation, and high ethoxycoumarin O-deethylation. The fourth form, P450 2B-B2, is catalytically distinct from the others, with activities characterized by high androstenedione 16 alpha- and 15 alpha-hydroxylation and high testosterone 16-hydroxylation. Since P450 2B-B2 is catalytically distinct from the other forms, the metabolic profiles of phenotypes that include P450 2B-B2 might differ significantly from those of phenotypes that lack P450 2B-B2. PMID- 8346921 TI - Ascorbic acid inhibition of cytochrome P450-catalyzed uroporphyrin accumulation. AB - Previous studies on the mechanism of the uroporphyria caused by polyhalogenated aromatic hydrocarbons have indicated a key role of cytochrome P450 of the 1A subfamily in catalyzing uroporphyrinogen (UROgen) oxidation. Here we report that ascorbic acid (ASC) inhibits UROgen oxidation in primary cultures of chick embryo hepatocytes and hepatic microsomes from chickens and mice. In hepatocyte cultures, 0.15 mM ASC totally prevented the accumulation of uroporphyrin (URO) induced by treatment of cells with the combination of 3,4,3',4' tetrachlorobiphenyl (TCB) and 2-propyl-2-isopropylacetamide (PIA), but had no effect on the induction of protoporphyrin accumulation by PIA and desferrioxamine. However, addition of 5-aminolevulinic acid (ALA) to cultures treated with PIA plus TCB decreased the ability of ASC to prevent URO accumulation, suggesting that the effectiveness of ASC was dependent on the intracellular concentration of ALA or its metabolites. Similarly, when chick hepatocyte cultures were treated with TCB plus exogenous ALA to produce URO accumulation, the effectiveness of ASC was also less than when ALA was produced endogenously. Under this condition, addition of piperonyl butoxide, a P450 inhibitor, increased ASC inhibition of URO accumulation. ASC competitively inhibited the oxidation of UROgen by hepatic microsomes from chicks or mice treated with 3-methylcholanthrene (MC) with Ki for ASC being about 0.1 mM. ASC prevented formation of a 500-nm absorbing compound, probably tetrahydrouroporphyrin, the first intermediate in UROgen oxidation. These results are consistent with ASC preventing URO accumulation in hepatocytes by competitive inhibition of the first step of UROgen oxidation and suggest a new physiological role of ASC, that of maintaining UROgen in the reduced state. PMID- 8346922 TI - Post-translational processing and membrane association of the two early endosome associated rab GTP-binding proteins (rab4 and rab5). AB - The two early endosome-associated rab GTP-binding proteins, rab4 and rab5, are suggested to regulate endocytosis. In this report, we examined post-translational processing and membrane association of the two rab proteins. Human rab4 and rab5 were expressed in chicken embryo fibroblasts using a Sindbis virus expression vector. Cells were labeled with either [35S]methionine or [3H]mevalonolactone. Cell lysates were immunoprecipitated with antisera specific for rab4 and rab5, respectively, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was found that both rab4 and rab5 contained at least three forms: the precursor form, the isoprenylated intermediate, and the isoprenylated mature form of faster mobility. The rab5 intermediate comigrated with the precursor form, whereas the rab4 intermediate migrated slightly faster than the precursor form. The intermediate form of rab4, but not rab5, accumulated in the presence of a chymotrypsin-like protease inhibitor (N-acetyl Tyr ethyl ester), suggesting that proteolysis was required for generation of the mature form. Furthermore, the intermediate and mature forms of rab4, but not rab5, were carboxyl-methylated as demonstrated by incorporation of alkali-labile counts from [methyl-3H]methionine. Membrane association of the distinct rab4 and rab5 forms was examined by subcellular fractionation and Triton X-114 partitioning. The precursor forms were found in the cytosol and partitioned into the aqueous phase. The mature forms were membrane-associated and partitioned into the detergent phase. Unexpectedly, the isoprenylated intermediate forms of both rab4 and rab5 partitioned exclusively into the aqueous phase. Taken together, the data indicate that the entire post-translational processing, which includes isoprenylation, carboxyl methylation (rab4), and possibly proteolysis, confers the competency for membrane association of rab4 and rab5. PMID- 8346923 TI - Alkaline lipase in rat intestinal mucosa: physiological parameters. AB - The present studies describe an alkaline active lipase in the rat intestinal mucosa. Alkaline lipase activity was determined using a glyceryl tri[14C]oleate emulsion at pH 8.0. Subcellular fractions were prepared from mucosal homogenates by differential centrifugation. Cells from villus to crypt were sequentially released using citrate and EDTA buffer. The enzyme was found to be most active in the proximal quarter of the intestine and in villus tips. Most of the activity was found in the cytosolic fraction. Bile salts stimulated the enzyme activity threefold. The presence of both Ca2+ and taurocholate was essential for optimal activity. Mucosal activity was greatly reduced on intraduodenal glyceryl trioleate infusion. Activity was restored when phosphatidylcholine was added to the glyceryl trioleate infusion. The fact that mucosal lipase has its greatest activity in the villus tips of the proximal intestine and in cytosol suggests that it may play an important role in mucosal glyceryltrioleate metabolism. PMID- 8346924 TI - Partial purification and characterization of phosphoenolpyruvate carboxylase protein-serine kinase from illuminated maize leaves. AB - Following in situ renaturation and assay of protein kinase activity after denaturing electrophoresis of relatively impure samples of maize phosphoenolpyruvate carboxylase (PEPC) kinase, a approximately 30-kDa polypeptide was implicated as the best candidate for the PEPC kinase catalytic subunit. This kinase's apparent native molecular weight was estimated at 28,000 by gel filtration on a calibrated Superose 12 column (HR 10/30), suggesting that the isolated PEPC kinase is monomeric. This protein-serine kinase was partially purified about 4000-fold from illuminated maize leaves by ammonium sulfate precipitation and sequential chromatography on Ultrogel AcA 54, hydroxylapatite, blue dextran-agarose, and an analytical AcA 54 column. Analysis by denaturing electrophoresis revealed that a 30-kDa polypeptide copurified with PEPC kinase activity during the final step. This highly purified kinase had an apparent Km (PEPC subunit) of 2.5 microM and a Km (total ATP) of 40 microM at pH 8.0, its pH optimum. Upon in vitro phosphorylation of darkform (dephospho) C4 PEPC at Ser-15 (maize PEPC) or Ser-8 (sorghum), the malate sensitivity of the target enzyme decreased significantly. The maize PEPC kinase activity was markedly inhibited by L-malate, a negative allosteric effector of its protein substrate, in a concentration- and pH-dependent manner. Comparative phosphorylation studies with the catalytic subunit of mammalian cAMP-dependent protein kinase and casein revealed that a significant part of the malate inhibition of PEPC kinase activity in vitro was due to this effector's interaction with PEPC. The activity of both the highly purified PEPC kinase and a less pure sample prepared rapidly in the presence of various protease inhibitors was insensitive to Ca2+ chelation or addition. It is concluded that the approximately 30-kDa maize PEPC kinase is a low abundance, Ca(2+)-independent protein-serine kinase that activates its target enzyme by the exclusive phosphorylation of the regulatory serine residue near the N terminus and the resulting decrease in feedback inhibition by L-malate. PMID- 8346925 TI - Hormonal regulation of platelet-activating factor-acetyltransferase activity in rat tissues. AB - Platelet-activating factor (PAF) plays a very important role in a number of physiological or pathological conditions. Recently, we and others have suggested that the PAF concentration in various tissues may be regulated by the enzyme that inactivates PAF, PAF acetylhydrolase (PAF-AH). Furthermore, it has been shown that the plasma isozyme of PAF-AH is regulated by various steroid hormone. Lyso PAF:acetyl-CoA acetyltransferase (PAF-AT) is a key enzyme in PAF biosynthesis by the remodeling pathway. In the present study, the hormonal effects on the tissue levels of PAF-AT activity were investigated in various organs of the rat. The microsomal fraction was prepared from the spleen, lung, uterus, and liver of female rats which had been pretreated with dexamethasone, 17 alpha ethynylestradiol, medroxyprogesterone-acetate, or vehicle and the PAF-AT activity was assayed. The rats treated with dexamethasone demonstrated significantly lower PAF-AT specific activity in the liver (P < 0.001) and spleen (P < 0.01), compared to the control group. A dose-dependent decrease of PAF-AT specific activity was demonstrated following dexamethasone treatment. Medroxyprogesterone injection also caused a significant decrease of PAF-AT activity in the liver (P < 0.01). No change of PAF-AT activity in any tissue was observed in the 17 alpha ethynylestradiol-injected animals. Plasma PAF-AH activity was increased significantly by the administration of dexamethasone (P < 0.001) or medroxyprogesterone (P < 0.001), and decreased by 17 alpha-ethynylestradiol (P < 0.001), as previously described. The observation that dexamethasone or medroxyprogesterone treatment decreases the activity of PAF-AT and increases the plasma PAF-AH activity provides a mechanism for the tight control of PAF in tissues. PMID- 8346926 TI - Purification and properties of laminaribiose phosphorylase (EC 2.4 1.31) from Euglena gracilis Z. AB - Three isoforms of laminaribiose phosphorylase, F0, F1, and F2, were purified to an electrophoretically homogeneous state from a cell free extract of Euglena gracilis Z (IAM E-6). F1 and F2 were the major components. The three enzymes showed very similar properties except their isoelectric points. They could also use laminaribiose as the glucosyl acceptor instead of glucose. The isoforms the same molecular mass of 120 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) or 200 kDa by the gel filtration method, suggesting that they have a dimer structure. They could not be distinguished on the Ouchterlony's double diffusion test with mouse antiserum against F1 or F2. The substrate specificities of F1 and F2 were determined to be essentially the same. Both of the reaction mechanisms of F1 and F2 were determined to be ordered bi-bi mechanisms, as in the case of cellobiose phosphorylase. A competitive substrate inhibition was observed in their synthetic reaction. Two other strains, E. gracilis var. bacillaris (IAM E-2) and E. gracilis (IAM E-3), had only one laminaribiose phosphorylase, which corresponded to F0 on native PAGE. PMID- 8346928 TI - [The functions of stress proteins in recent research]. AB - Stress proteins are highly conserved among all living organisms and play important roles in protection of cells against environmental stresses. At the same time, stress proteins function also in cells under normal conditions as molecular chaperones in assisting cellular proteins in folding and assembly. PMID- 8346927 TI - Glucose utilization by tumor cells: the enzyme hexokinase autophosphorylates both its N- and C-terminal halves. PMID- 8346929 TI - [Chemotherapy for the treatment of angiosarcoma]. AB - A common type of angiosarcoma in the dermatological field is Wilson-Jones type angiosarcoma arising on the head and neck of elderly. It is called malignant hemangioendothelioma (MHE) and its prognosis is extremely poor, even though treated with the present state of the art: surgical excision, radiation, chemotherapy, and immunotherapy. Recently, chemotherapy has been done with CYVADIC (CPM, VCR, ADM, DTIC), and in some cases intraarterial fusion of ADM and 5-FU has been tried in combination therapy. But older patients are particularly intolerant of this chemotherapy, because of its severe toxic effects. Unfortunately, there is no evidence that these chemotherapeutic trials have helped to improve the prognosis. PMID- 8346930 TI - [Intraperitoneal chemotherapy of CDDP and etoposide in patients with advanced ovarian cancer]. AB - Intraperitoneal disseminated ovarian cancer has a poor prognosis and its treatment is difficult. Recently, we undertook intraperitoneal chemotherapy (IP) of CDDP (Pt) and etoposide (Et) using an implantable reservoir. The subjects were 14 patients with advanced ovarian cancer. One hundred mg of Pt and 200 mg of Et were administered intraperitoneally through the reservoir, and the therapeutic results were evaluated. In 6 patients, levels of total platinum (t-Pt), free platinum (f-Pt) and Et were determined in the blood and intraperitoneal fluid by flameless atomic absorption spectrophotometry. 1. The 14 patients received 82 courses of IP. In 10 cases of IIIrd stage, no recurrence was detected in 5 radical operable cases, and 4 of 5 inoperable cases were able to undergo radical operation after IP. One case was inoperable even after IP. Recurrences were detected in 2 of 4 cases which subsequently became operable. In a case of IVth stage, remission was achieved, but the tumor markers began rising again 18 months after operation. No further recurrence was detected in a treated recurrence case. In 2 cases of metastatic cancer, recurrences were detected 3 and 7 months after operation, respectively. As a side effect, the incidence of gastrointestinal toxicities, anemia, leukocytopenia and alopecia was high, but the grade was almost 1 or 2. Intraperitoneal mean maximum concentrations were t-Pt: 21.98 +/- 5.78; f-Pt: 17.72 +/- 4.97; Et: 62.98 +/- 23.94 micrograms/ml. Blood mean maximum concentrations were t-Pt: 2.84 +/- 0.41; f-Pt: 0.84 +/- 0.22; Et: 11.38 +/- 2.12 micrograms/ml. Mean AUC of the blood were t-Pt: 57.76 +/- 6.62; f-Pt: 2.96 +/- 0.47; Et: 108.76 +/- 18.94 micrograms.h/ml. 2. IP is considered to be effective for advanced ovarian cancer not only as a local therapy but as a general therapy, and is feasible as maintenance therapy with the implantable reservoir and tolerable side effects. PMID- 8346931 TI - [Clinical results of repeated intraperitoneal administration of CDDP in patients with ovarian cancer]. AB - CDDP was intraperitoneally administered to 45 ovarian cancer patients (9 cases in Stage Ic, 9 cases in Stage II, 19 cases in Stage III and 8 cases in Stage IV) as the first line chemotherapy to examine response rates and cumulative survival rates by Kaplan-Meier method. Among 18 cases with measurable tumor, there were 5 CR cases, 6 PR cases, 4 NC cases and 3 PD cases. Eleven out of 18 responded, for a response rate of 61.1%. The 3- and 5-year survival rates were 88.9% and 88.9% in Stage I, 46.7% and 0% in Stage II, 48.6% and 41.7% in Stage III, and 0% and 0% in Stage IV, respectively. The 3- and 5-year survival rates in patients with residual tumor smaller than 2 cm in diameter after the first surgery in Stage III or IV were 76.9% and 61.4% respectively, in contrast to 11.5% and 11.5% in patients with residual tumor of 2 cm or larger in diameter. Thus, a significantly better prognosis was demonstrated in patients with residual tumor smaller than 2 cm. These results indicate that intraperitoneal administration of CDDP demonstrated high response rates and proved to be useful as the first line chemotherapy, yet did not manage to improve the long-term prognosis of patients with progressive cancer. PMID- 8346932 TI - [Clinical efficacy of cis-diamminedichloroplatinum [II] and 5-fluorouracil (UFT) in advanced cancer of the alimentary tract]. AB - A clinical study of the combination of cis-diamminedichloroplatinum [II] (CDDP) and 5-fluorouracil derivatives was conducted in advanced cancer of the alimentary tract. The regimen consisted of CDDP 50 mg/body/day (day 1-2, continuous infusion), 5-fluorouracil 500-750 mg/body/day (day 2-7, continuous infusion) and UFT 400 mg/day (day 8-28) on 1-3 courses. Thirty patients could be evaluated. The response rate was 25% (2/8) in cases of esophageal cancer, 31% (4/13) in gastric cancer and 33% (3/9) in colorectal cancer, with an overall response rate of 30% (9/30). A comparatively higher response rate was obtained in lymph node metastases (46%) and liver metastases (50%). Anorexia, nausea/vomiting and leukocytopenia were frequently observed, but almost all were well tolerated and recovered except two cases with severe leukocytopenia and nephrotoxicity. Based on these results, this combination chemotherapy seems to be useful for advanced cancer of the alimentary tract. PMID- 8346934 TI - [Prophylactic effect of methylprednisolone on cisplatin-induced nephrotoxicity in rats]. AB - Cis-diamminedichloroplatinum (II) (cisplatin) is a very effective antitumor drug, but It has an adverse effect of nephrotoxicity. There are many reports concerning protective agents against cisplatin nephrotoxicity, but clinically useful modalities are very few. In the present study, prophylactic effects of methylprednisolone (MP) on cisplatin-induced nephrotoxicity were examined. Male Sprague-Dawley rats were injected iv with 6.5 mg/kg of cisplatin combined with a subcutaneous MP given sc in various doses at various timing. Rats were killed 5 days after cisplatin injection to determine BUN and serum creatinine levels. BUN and serum creatinine levels in rats pretreated with MP 4 or 2 hr before cisplatin injection were significantly lower than those in rats received cisplatin alone. Our preliminary results suggest that pretreatment with MP is an effective means of protection against cisplatin-induced nephrotoxicity. PMID- 8346933 TI - [Tissue and serum levels of 5-FU in the patients with head and neck malignant tumors--influence of a streptococcal preparation OK-432]. AB - Concentrations of Tegafur, 5-FU, and Uracil were measured in the tissues and serum of 32 patients with malignant head and neck tumors after administration of UFT or UFT and OK-432. Of the 32 patients, 15 patients were treated with UFT alone and 17 patients with a combination of UFT and a clinical dose of OK-432. The level of 5-FU was higher in the tissues and serum in the patients who received the combined administration of UFT and OK-432 than in those the received UFT alone. In particular, levels of 5-FU in tumor tissue and metastatic lymph node tissue were higher than 0.05 micrograms/g even 14.6 hours after the last administration of UFT. No significant undesirable interactions between UFT and OK 432 were exhibited during combination therapy of these agents in clinically administered doses. From our satisfactory results, clinical cures would be expected by the combined immuno-chemotherapeutic action of these agents. PMID- 8346935 TI - [Photodynamic therapy (PDT) in roentgenographically occult lung cancer by photofrin II and excimer dye laser]. AB - Patients (pts) with hilar type early lung cancer from 5 hospitals served as the subjects to assess the complete response rate and toxicity of PDT with Photofrin II (PHE) and excimer dye laser (PDT EDL-1). ENTRY CRITERIA: 1. Histologically proven lung cancer with endoscopically superficial thickening or small protrusion. 2. All lesions that were located proximally from the subsegmental bronchus, were visible to the distal margin of the lesions. 3. N0M0. METHOD: All pts received PHE (2 mg/kg) i.v., 48 hours before PDT. Tumor lesions superficially photoradiated by an excimer dye laser via flexible bronchoscope. RESULTS: From September 1990 to March 1992, 39 pts with 46 carcinomas (CA) were enrolled. Thirty-three pts with 40 CA were evaluable. 1. RESPONSE: Thirty-five in 40 CA showed a complete response (CR) (87.5%, 95% confidence limit: 73.2-95.8%). All 32 cases of CA equal to or less than 1 cm of tumor length were CR, but 3 CA relapsed locally. Thirty-three of 35 CA visible to the distal margin were CR (91.7%, 95% confidence limit: 77.5-98.3%). 2. Toxicity (> WHO grade 2): Three pts (7.7%) had transient dermatitis and sunburn, while another pt (2.6%) had symptoms due to obstructive pneumonitis. CONCLUSIONS: Tumors equal to or less than 1 cm in length and visible to the distal margin are curable by PDT. PMID- 8346936 TI - [Six cases of therapy related leukemia; case reports and review of the literature]. AB - The following presents 6 cases of therapy related leukemia (TRL) along with discussion of their clinical features in comparison with those previously reported in Japan. Common primary malignancies were mammalian cancer, lung cancer and malignant lymphoma in both groups. It was observed that, 1) average age was higher (68 years), 2) average latent period from primary malignancy to leukemia was longer (10 years), particularly in patients treated solely with radiation, 3) in 4 out of 6 patients (67%) karyotype analysis of leukemia cells showed normal results, but in one case previously administered etoposide, translocation involving 15q+, 17q- was noted, and 4) the CR ratio in our cases was 83%; half the cases are still alive at 10 months of follow-up, while in previously reported cases the CR ratio was 41%, and the median survival time was 12 months according to Kaplan-Meier analysis. Although poor response to conventional chemotherapy has been reported in TRL patients, the present data indicated TRL in some cases to achieve complete response and long-term survival. Aggressive chemotherapy should be considered for such patients. PMID- 8346937 TI - [Growth rate analysis of pulmonary metastases in giant cell tumor of bone]. AB - We reviewed six cases with pulmonary metastases in giant cell tumor of bone. The growth rate and the doubling time of pulmonary metastases was measured and compared to the clinical course. The six cases were classified into two each of the following three types: 1) spontaneous remission, 2) continuously slow growing and 3) rapid growing. A favorable factor was a doubling time of more than 80 days in pulmonary metastases. A poor prognosis was indicated by a doubling time of around 30 days. Aggressive primary lesions should be excised widely. PMID- 8346938 TI - [Successful chronic daily administration of oral etoposide for a case of adult T cell leukemia]. AB - A 54-year-old woman with leucocytosis and skin lesion was hospitalized and diagnosed as chronic type adult T cell leukemia (ATL) in August 1989. Since her ATL cell count and LDH level increased after hospitalization, oral administration of etoposide was started at a dose of 100 mg/day for seven days. The oral administration of etoposide induced another chronic state of ATL. After 10 months without medication, she was readmitted because of an acute ATL crisis. After daily administration of etoposide at a dose of 50 mg/day, the white blood cell count and serum LDH level decreased to the normal range, and abnormal lymphocytes of peripheral blood disappeared. The low-dose daily administration of etoposide at a dose of 25 approximately 50 mg/day could be maintained over six months. No severe side effects except for alopecia and mild myelosuppression were noted during the treatment. Chronic daily administration of oral etoposide is one candidate for the treatment of ATL in an outpatient clinic. PMID- 8346940 TI - [Role in mucosal ornithine decarboxylase activity during dimethylhydrazine induced colonic carcinogenesis in the rat]. PMID- 8346939 TI - [Successful oral administration of etoposide therapy for refractory malignant lymphoma treated with frequent combination chemotherapy]. AB - A 67-year-old man was diagnosed as non-Hodgkin lymphoma (diffuse, mixed cell type, B cell) with clinical stage IV in March 1989. He had been treated many times with salvage chemotherapy on admission including CHOP-etoposide and ProMACE Cyta BOM. Recurrence, however, occurred in two or three months after any therapy. He had a therapeutic history of chronic daily administration of etoposide. In November 1991, recurrence was found in the peripheral lymph node and the colon. A new regimen of oral administration of etoposide, 50 mg/day four times a week, was employed. Two months later, the peripheral lymph node swelling disappeared. Seven months later, the patient showed no signs of recurrence by Ga-scintigraphy. This therapy is being continued. It is suggested that anti-neoplastic activity of etoposide is dependent on the schedule of administration. This regimen is suggested to be effective in the treatment of patients with refractory malignant lymphoma. PMID- 8346941 TI - [A comparison of 5-fluorouracil concentration of 5-fluorouracil drip infusion versus orally UFT in plasma of same patients]. PMID- 8346942 TI - [Endocrine therapy for breast cancer. Round table discussion]. PMID- 8346943 TI - [Functions of antioncogene products]. AB - Inactivation of antioncogenes result in the generation of tumor cells. Recent progress in molecular biology of antioncogenes enabled us to study the function of the products of RB, WT, p53, NF1, DCC, APC and MCC genes. Analyses of the function of these proteins will give us an insight into the mechanisms of cell transformation. PMID- 8346944 TI - Fetal activity, behaviour, and neurology: fact or fiction? PMID- 8346945 TI - Prospective surveillance of neonatal meningitis. AB - Neonatal meningitis is a serious problem with a high mortality and frequent neurological sequelae. The incidence of neonatal meningitis was calculated and the aetiology, clinical and laboratory features, and the treatment of cases recorded prospectively over a 7 year 8 month period was documented. It was further investigated whether secondary meningitis had occurred after lumbar puncture. The estimated incidence of bacterial, viral, and fungal meningitis was 0.25, 0.11, and 0.02 per 1000 live births respectively. There were eight cases of early onset meningitis (seven definite, one probable) and group B streptococci accounted for six (75%) of these. Blood cultures were negative in only one of seven cases of definite early bacterial meningitis. Of the 15 late onset cases, Gram negative organisms accounted for six of the seven bacterial cases. The overall mortality was 26%. Of the 11 survivors of bacterial meningitis, three (27%) had significant neurological sequelae at follow up (between three months to three years later). As in the first 48 hours after birth an initial blood culture is unlikely to be negative if bacterial meningitis is present, lumbar puncture can be deferred if the procedure might exacerbate respiratory distress. Although approximately 1880 infants had a lumbar puncture during the review period, only one case of meningitis was found where it was possible that lumbar puncture in a bacteraemic infant may have caused meningeal infection. The incidence of this potential complication must therefore be low. PMID- 8346946 TI - Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity. AB - The effectiveness of recombinant human erythropoietin (r-HuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the r HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose r HuEpo can produce significant gains in red cell production that may be clinically useful. PMID- 8346948 TI - Dilution kinetics of H(2)18O for the measurement of total body water in preterm babies in the first week after birth. AB - The aim of this study was to determine the kinetics of H(2)18O equilibration and elimination in preterm babies for the estimation of total body water. Thirteen, clinically stable, preterm babies of less than 32 weeks' gestation were studied in the first week after birth. Blood and urine samples were obtained for baseline measurement of 18O:16O ratio and 1 ml/kg of 10% H(2)18O (0.1 g/kg isotope) administered orally. Eleven blood samples were obtained over the next six hours and between one and four over the next 18 hours. During the same 24 hour period between three and eight urine samples were also obtained. The dilution space at zero time (volume of distribution or total body water) was estimated using double exponential curve fitting using all available points, from single samples and from linear regression on the log data using two or three samples. Equilibration time was variable and showed a significant correlation with percentage change in body weight from birth. For blood samples, the median time to equilibrium was 81 minutes (range 2 to 191). A plateau phase was not detected, with H(2)18O enrichment declining after the point of maximum enrichment. The median volume of distribution at time 0, based on double exponential curve fit analysis, was 859 ml/kg (range 755 to 995). The volume of distribution, estimated from linear regression on the log data using two serum samples obtained at three and six hours, approximated most closely to that based on exponential curve fit analysis with a median difference of -4 ml/kg (range -41 to 73). It was concluded that in most situations blood sampling at three and six hours may be acceptable. However, as equilibration time is variable and influenced by the state of expansion or depletion of body water compartments, when studying overhydration states, multiple sampling is advised in order to be certain that the elimination phase has been reached. PMID- 8346947 TI - Urea kinetics in neonates receiving total parenteral nutrition. AB - Urea kinetics were measured on 10 occasions in eight neonates who had not received an oral intake from birth and were maintained on total parenteral nutrition. After a prime/intermittent oral dose of 15N15N-urea over 14 hours urine was collected every three to four hours, urea isolated, and kinetics determined from the plateau level of enrichment in urea, measured by isotope ratio mass spectrometry. The total parenteral nutrition provided 393 kJ (94 kcal)/kg/day and 360 mg nitrogen/kg/day. Urea production was mean (SD) 84 (44) mg nitrogen/kg/day, or 50% of intake. Urinary excretion of urea, 39 (16) mg nitrogen/kg/day, was 40% of production. Therefore 54% of urea production was salvaged through the lower bowel, 45 (35) mg nitrogen/kg/day. It is concluded that even in infants who have never had a regular dietary intake the microflora of the lower bowel is sufficiently developed to salvage urea nitrogen for further metabolic interaction, however it is not clear whether the rate of salvage is adequate to satisfy the metabolic demand. PMID- 8346949 TI - Can brain impairment be detected by in utero behavioural patterns? AB - Fetal behavioural patterns were examined to test whether they could be used to localise sites of brain damage antenatally. Decreased fetal movement, persistent nonreactive fetal heart rate (FHR) pattern, and/or central nervous system malformation were used as indicators of possible neurological impairment. Ten fetuses tested in this way underwent further ultrasound examination observing movement of the extremities, chest wall (breathing), and eye and mouth, and active/quiet FHR patterns. Eight of these 10 fetuses were found on postnatal examination to have a brain impairment. The fetuses having potential in utero brain impairment were divided into four groups: those with (1) lesion sites at, or caudal to, the pons-medulla that were specifically identified by fetal behaviour, (2) diffuse lesions in the brain which, although resulting in abnormal behaviour, could not be localised by this behaviour, (3) lesions localised in the cerebral hemisphere(s) but with no abnormal behaviour and (4) temporally abnormal behaviour in utero, finally changing over to a normal pattern with no neonatal neurological abnormality. A screening system for the antenatal assessment of brain impairment is thus proposed. PMID- 8346950 TI - Ultrasonic assessment of gastric emptying in the preterm infant. AB - The study of gastric emptying in the preterm infant has been hampered by the absence of a suitable, valid technique. We have evaluated gastric antral clearance using serial ultrasonic measurement of the antral cross sectional area (ACSA). The study was easy to perform, providing successful results in 15 of 17 low birth-weight infants, with feed volumes of 8-31 ml/kg. ACSA was closely related to intragastric volume (mean (range) r = 0.96 (0.89-0.99)). Measurements were reproducible: mean (SE) coefficient of variation was 7.7% (1.1). Gastric antral clearance was observed as a fall in ACSA that began shortly after completion of the feed and returned to prefeed values at a variable rate. The pattern of gastric antral transit was entirely consistent with recognised patterns of gastric emptying and half gastric antral clearance times ranged from 20-63 minutes. Ultrasonic measurement of gastric antral clearance is a new technique allowing the study of gastric emptying in the preterm infant. PMID- 8346951 TI - The effect of intravenous ranitidine on the intragastric pH of preterm infants receiving dexamethasone. AB - Gastric perforation is a catastrophic, albeit uncommon, side effect of steroid treatment for premature infants with bronchopulmonary dysplasia (BPD). A reduction of intragastric acidity may protect against peptic ulceration. The effect of different doses of ranitidine, given as intravenous infusions, on intragastric acidity in premature neonates was therefore examined. Ten consecutive, enterally starved, infants receiving dexamethasone (0.6 mg/kg) for BPD were enrolled. Intragastric pH was continuously monitored on the day before steroid treatment and on the four following days, initially without H2 blockade and then using a continuous intravenous infusion of ranitidine at 0.031, 0.0625, and 0.125 mg/kg/hour. An infusion of 0.0625 mg/kg/hour of ranitidine was sufficient to increase and maintain gastric pH above 4; the authors therefore use this infusion during dexamethasone administration as possible prevention of gastric perforation. PMID- 8346952 TI - Inflammatory cells in the lungs of premature infants on the first day of life: perinatal risk factors and origin of cells. AB - Neither the origin of leucocytes in the premature newborn airway nor their relationship to perinatal factors has been adequately determined. In order to sample airway cells, modified bronchoalveolar lavage was performed on 74 intubated infants of < 32 weeks' gestation and < 24 hours of age. Cells were counted, stained and, in a small separate group of six infants, four boys and two girls, probed for the Y chromosome with suitable control samples. Perinatal risk factors for increased airway cellularity were analysed by multiple regression. Premature rupture of membranes of more than 24 hours' duration was independently associated with increased numbers of airway leucocytes (n = 74). More than 90% of airway leucocytes from four boys with pulmonary inflammation were positive for the Y chromosome indicating that the cells were of fetal rather than maternal origin. PMID- 8346953 TI - Pulmonary inflammatory cells in ventilated preterm infants: effect of surfactant treatment. AB - The aim of this study was to determine the effect of surfactant treatment on the number and distribution of inflammatory cells in bronchoalveolar lavage fluid (BALF) from mechanically ventilated preterm infants over the first week of life in relation to the subsequent development of chronic lung disease (CLD). The study included 25 babies who received surfactant on clinical grounds and 29 babies of similar severity who did not. BALF was collected on days 1, 3, 5, and 7 after birth. Cell counts were performed and differentials were calculated on 300 cells. CLD was equally common in both treatment groups. Of the 54 infants, 29 (53%) who developed CLD had a higher incidence of patent ductus arteriosus and air leak and needed a higher concentration of inspired oxygen on the fifth and seventh days of life. Babies who developed CLD had more polymorphonuclear leucocytes and fewer macrophages on days 5 and 7 than those who recovered. Surfactant treatment was associated with a higher total white cell count on day 3. Between days 3 and 7, macrophage numbers were higher in surfactant treated babies, whatever the pulmonary outcome. This data suggests that CLD was associated with persistence of high numbers of polymorphonuclear leucocytes in BALF at the end of the first week. Surfactant treatment caused a persistent increase in macrophage numbers. The association between persistent neutrophilia and CLD was unaffected by surfactant treatment. PMID- 8346954 TI - Bronchoalveolar lavage fluid glutathione in intubated premature infants. AB - Lower concentrations of uncorrected glutathione in the bronchoalveolar lavage fluid were found on the first day of life in seven infants who subsequently developed chronic lung disease when compared with 27 infants who did not require supplemental oxygen at 36 weeks' postconceptional age. The concentration of glutathione on the first day was independent of gestational age. These preliminary results suggest that glutathione accumulates in the lung epithelial lining fluid of preterm infants and that a relative deficiency may predispose to lung injury. PMID- 8346955 TI - Aminophylline and increased activity of peripheral chemoreceptors in newborn infants. AB - Peripheral chemoreceptor activity was studied in nine healthy, unsedated neonates (with a mean (SD) postconceptional age of 39 (2) weeks and birth weight of 3000 (400) g) by measuring the inhibition of ventilation elicited by five breaths of 100% oxygen (Dejours technique). Changes in tidal volume, frequency, and minute ventilation were measured before and after administration of aminophylline (10 mg/kg by mouth). Before aminophylline hyperoxia induced a decrease in minute ventilation (from a mean (SE) of 825 (55) to 520 (30) ml/kg/min) as result of reduction of tidal volume (from 12 (0.3) to 8 (0.3) ml/kg). After aminophylline administration the hyperoxia induced decrease in tidal volume (from 14 (0.7) to 6 (0.3) ml/kg) and minute ventilation (from 847 (57) to 386 (21) ml/kg/min) was significantly greater than before. It is concluded that in neonates peripheral chemoreceptors are more active in the presence of aminophylline. It is speculated that aminophylline increases the activity of peripheral chemoreceptors, reducing the breakdown of cAMP, which is a crucial mediator for peripheral chemoreceptor discharge. PMID- 8346956 TI - Pharmacokinetics of morphine infusion in premature neonates. AB - Morphine pharmacokinetics were studied in 17 premature neonates (26-34 weeks' gestation) after intravenous infusion during the first 24 hours of life. Infants received either standard dose morphine that comprised of a 100 micrograms/kg/hour loading infusion for 2 hours followed by a maintenance infusion of 12.5 micrograms/kg/hour, or a high dose of 200 micrograms/kg/hour for 2 hours followed by 50 micrograms/kg/hour. Mean plasma concentrations of morphine (SD) after 2 and 24 hours were 99 (12.9) and 96.4 (3.2) ng/ml, and 184.2 (37.7) and 319 (71.2) ng/ml for the standard and high dose regimens, respectively. Morphine-3 glucuronide plasma concentrations achieved about 20% and 80% of morphine values at 2 and 24 hours respectively. Morphine-6-glucuronide could not be detected at 2 hours, but attained 20-25% of morphine plasma concentrations by 24 hours. The population mean morphine clearance was 2.4 ml/min/kg, the elimination half life was 8.75 hours and the volume of distribution was 1.82 1/kg. High plasma concentrations of morphine appeared to be well tolerated. Although mean arterial blood pressure decreased during the first six hours of treatment, this was not statistically significant; two infants experienced transient muscle rigidity, but no evidence of seizures was noted. There appears to be no clinical advantage in using the high dose regimen. PMID- 8346957 TI - Response to dobutamine and dopamine in the hypotensive very preterm infant. AB - A randomised double blind study was designed to evaluate haemodynamic response to dobutamine and dopamine in 20 hypotensive preterm infants of less than 32 weeks' gestation. Neonates initially received dopamine or dobutamine 5 micrograms/kg/min. If mean arterial pressure (MAP) remained below 31 mm Hg, the infusion rate was increased in increments of 5 micrograms/kg/min. If 20 micrograms/kg/min of the initial drug failed to achieve a MAP above 30 mm Hg, it was discontinued and the other drug was administered at the same infusion rate. Left ventricular output (LVO) was measured by pulsed Doppler echocardiography. Mean (SE) MAP increased significantly from 24.4 (1.0) to 32.0 (1.4) mm Hg at a median dobutamine dosage of 20 micrograms/kg/min and from 25.6 (1.2) to 37.7 (1.5) mm Hg at a median dopamine dosage of 12.5 micrograms/kg/min. The percentage LVO increase was +21 (7)% with dobutamine compared with -14 (8)% with dopamine. Dobutamine failed to increase MAP above 30 mm Hg in six infants out of 10, whereas dopamine succeeded in all 10 infants. Six switches from dobutamine to dopamine were thus performed, providing a rise in MAP (29.2 (0.5) to 41.2 (2.0) mm Hg) and drop in LVO (356 (40) to 263 (36) ml/kg/min). These data indicate that dopamine is more effective than dobutamine in raising and maintaining MAP above 30 mm Hg; however dopamine does not increase LVO. PMID- 8346958 TI - Cyclical variation of blood pressure and heart rate in neonates. AB - Using a computerised physiological monitoring system a cyclical variation in blood pressure (waves), with associated changes in heart rate and transcutaneous oxygen, was observed. Twenty five episodes were seen in 10 neonates, with a median gestation of 33 weeks (range 28-42 weeks). Eight neonates had an asphyxial injury. Blood pressure waves had a mean (SD) amplitude of 11.6 (5.6) mm Hg with a mean wavelength of 9.0 (5.2) minutes. Both amplitude and frequency were independent of gestation. In neonates of less than 34 weeks an inverse phase relation existed between heart rate and blood pressure waves (blood pressure rose as heart rate fell); in infants with a gestation greater than 34 weeks a direct phase relationship occurred (blood pressure and heart rate rose together). It is postulated that hypertensive blood pressure waves may cause or exacerbate cerebral pathology in neonates with a pressure passive cerebral circulation. PMID- 8346959 TI - Is specialist centre delivery of gastroschisis beneficial? AB - This study aims to establish the usefulness of delivering neonates with gastroschisis in a regional obstetric and neonatal centre without the facility of on site surgery. A retrospective analysis was performed on the notes of 43 consecutive neonates with gastroschisis referred to Birmingham Children's Hospital over a 10 year period. Two groups were compared: those delivered at the regional obstetric centre (n = 9) and those delivered peripherally (n = 34). Both groups underwent postnatal transfer. There were no significant differences with regard to gestational age, birth weight, caesarean section rate, time to operation, and mortality. Primary closure rates were 89% for the regional centre group and 94% for the peripheral hospital group. Mean time to full enteral feeding was 24 days for the regional centre group and 23 days for those delivered peripherally. These data show that good results can be achieved with postnatal transfer. If on site surgery is not available, neonatal services are adequate peripherally, and the transfer distance is not too great, then delivery in a regional obstetric centre with subsequent postnatal transfer offers no advantage. PMID- 8346960 TI - Changes in cerebral artery blood flow velocity after intermittent cerebrospinal fluid drainage. AB - Doppler ultrasound was used to measure blood flow velocity in the anterior cerebral artery of six premature infants with posthaemorrhagic hydrocephalus, before and after intermittent cerebrospinal fluid (CSF) drainage, on 23 occasions. There was a significant increase in mean blood flow velocity after the drainage procedures (+5.6 cm/s, 95% confidence interval +2.9 to +8.3 cm/s), which was accompanied by a decrease in velocity waveform pulsatility. CSF pressure also fell significantly. In patients with posthaemorrhagic hydrocephalus, intermittent CSF drainage was associated with acute changes in cerebral haemodynamics. PMID- 8346961 TI - Measurement of ionised calcium concentration in neonates. AB - Whole blood ionised calcium concentration was measured simultaneously in capillary and arterial blood from neonates being nursed on an intensive care unit using an ion selective electrode. The mean arterio-capillary difference was 0.027 mmol/l (95% confidence intervals -0.041 to -0.012 mmol/l) and the limits of agreement between the two measurements were 0.034 and -0.088 mmol/l. Measurement of ionised calcium in capillary blood is acceptable for clinical purposes. PMID- 8346962 TI - Inadvertent brain penetration during neonatal nasotracheal intubation. AB - During routine nasal intubation of a premature infant, the endotracheal tube penetrated the brain. Bloodstained cerebrospinal fluid and neural tissue was apparent. Initial cranial sonography was normal, but the infant later developed extensive intracranial haemorrhage. Rotation of an endotracheal tube to facilitate insertion angles the bevel at the tip upwards, increasing risk of brain penetration. Great care is required during nasal intubation; use of a small feeding tube over which to slide an endotracheal tube may be helpful. PMID- 8346963 TI - Nasal endotracheal intubation in a premature infant with a nasal encephalocele. AB - After a difficult nasal intubation a premature infant leaked cerebrospinal fluid (CSF) from one nostril. After developing bacterial meningitis, the baby was referred for neurosurgical management of the CSF fistula. Transaxial computed tomograms demonstrated a nasal encephalocele, but coronal scans were needed to show the defect in the cribriform plate. PMID- 8346965 TI - A method for urine collection in infants. AB - A simple, inexpensive, non-invasive method for urine collection was used in 28 consecutive infants for periods of 48 hours (n = 10) and 72 hours (n = 18). The incidence of urine collector detachment was low on the first and second days (< 4%) and increased significantly on the third day (28%). Volume of urine leaked was < 4% of the total volume collected daily. This method is applicable to both sexes and is reliable for up to 48 hours. PMID- 8346964 TI - Urea salvage in a neonate with cloacal exstrophy. AB - Urea kinetics were measured in a child with congenital absence of the colon on days 15, 19, and 23 of age. Urea salvage was 5% of urea production in the first study, increasing to 79% by the third. This provides evidence that the colonic microflora play a more active part in urea salvage than the mucosa and that the establishment of an active lower ileal microflora takes over some of the metabolic functions of the intact colon. PMID- 8346966 TI - Sodium intake and preterm babies. PMID- 8346967 TI - Duration of periventricular densities in preterm infants and neurological outcome at 6 years of age. AB - Parenchymal echogenicities that break down into extensive cystic lesions are generally followed by severe motor deficit. However, the effect of echodensities in the periventricular white matter, so called 'flares', on later development is less well documented. The aim of the present study was to investigate the impact of neonatal flares in preterm infants on neurological status and motor competence at 6 years of age and to see to what extent outcome was related to duration of flares. Forty four children with flares, subdivided into three groups according to the duration of flares, and 62 children with normal scans were assessed on Touwen's neurological examination, the Movement ABC, and the British Ability Scales. No differences in cognitive abilities were found between the groups. The results of the motor assessments showed that performance decreased significantly with increasing duration of flares. In addition, there was a suggestion that this trend was stronger in measures assessing lower limb function than those of upper limb. Teachers were also able to identify differences between the groups of children on the basis of their motor performance in school. PMID- 8346968 TI - Spinal cord birth injury--diagnostic difficulties. PMID- 8346969 TI - Dr Alfred Hart (1888-1954) of Toronto and exsanguination transfusion of the newborn. PMID- 8346970 TI - Toxic potential of non-ortho and mono-ortho coplanar polychlorinated biphenyls in Aroclors, seals, and humans. AB - Mono-ortho and non-ortho coplanar polychlorinated biphenyls (PCBs) were analyzed in Aroclors, seals, and humans by graphitized carbon, a recently developed HPLC method (Hong et al. 1992b) and high-resolution gas chromatography with electron capture detection (HRGC/ECD). The concentration data were multiplied by potency factors derived from aryl hydrocarbon hydroxylase (AHH) induction to give 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) equivalents. The ability to separate coplanar PCBs from the majority of PCBs has allowed the use of TCDD toxicity equivalence to compare the relative dioxin-like potency of PCB residues in the complex mixtures. The most active mixtures, Aroclors 1254, 1248, and 1242, contained 42 54% by weight of chlorine. The results demonstrate that the apparent dioxin-like potency of PCB residues in Aroclors, seals, and humans is dominated by three congeners, 3,3',4,4'-tetra-, 2,3,3'-4,4'-, and 3,3',4,4',5-pentachlorobiphenyl (IUPAC nos. 77, 105, 126). PMID- 8346971 TI - Dentin as a possible bio-epidemiological measure of exposure to mercury. AB - The subtle human health effects from prolonged exposure to small amounts of mercury vapor are unknown. It has been difficult to study possible effects of low dose exposure for lack of a good measure of long-term exposure. Current methods which use blood, urine, hair, and nails reliably measure only recent exposures. Long-term exposure to lead has been measured using levels found in human dentin. The purpose of this study was to determine whether mercury also accumulates in dentin. In this study, dentin from 16 human teeth, all without dental amalgam restorations, was analyzed by thermal neutron activation analysis. The teeth were selected from people with and without dental mercury amalgam restorations elsewhere in their dentitions. Mercury was found in amounts up to 5.9 ppm. While the highest mercury level was from a sample from someone who had dental amalgam restorations elsewhere in their dentition, the second highest was from someone who had no amalgam restorations. Also, a sample which was not used for any statistical comparisons but which was analyzed because the tooth contained an amalgam restoration had one of the lowest levels of mercury. These results, while inconclusive due to a small sample size, suggest that inorganic mercury vapor is a relatively small contributor to the overall body burden of mercury. PMID- 8346972 TI - Exposure-excretion relationship of styrene and acetone in factory workers: a comparison of a lipophilic solvent and a hydrophilic solvent. AB - A factory survey was conducted in the second half of a working week on 41 exposed male workers, who were engaged in fiber-reinforced plastics work and exposed to the mixed vapors of styrene and acetone. Nonexposed workers, 20 men, were recruited from the same factory. Styrene and acetone in respiratory zone air were monitored for a 8-h shift with carbon cloth- and water-equipped personal diffusive samplers, respectively. Blood and urine samples were collected at the shift-end. Acetone and styrene concentrations in whole blood, serum and urine were measured by head-space gas chromatography, and phenylglyoxylic acid in urine by high-performance liquid chromatography. All biological exposure indicators analyzed correlated significantly with the intensity of exposure to the corresponding solvent during the shift. The slopes of the regression lines indicate that a very small fraction of styrene absorbed will be excreted into urine as styrene per se, and that styrene is quite effectively excreted into urine after metabolic conversion. In contrast, the slopes of regression lines for acetone suggest that acetone distributes both in the blood and urine quite evenly. When the distribution of the solvent in serum was compared with that in the whole blood, it was found that almost all of styrene in blood is present in the serum, whereas acetone distributed very evenly in the cellular and noncellular fractions of the blood. PMID- 8346973 TI - Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome. AB - In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was recognized in the United States. Physicians in New Mexico linked the epidemic to the ingestion of L tryptophan (LT). Results of studies indicated that one or more trace contaminants in LT were likely causes of the EMS epidemic. Investigators traced the LT that was taken by most patients with EMS to a single manufacturer, Showa Denko K.K. of Japan. We now report results of high performance liquid chromatographic analysis of LT samples from this manufacturer. Three sets of blind-coded samples were analyzed: the priority case lot set, which included 54 case-associated LT lots and 50 noncase-associated LT lots that were taken by case and control subjects who used only one brand of LT; the single lot case set, which included 73 case associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included LT tablets taken by case subjects (n = 26) and by control subjects (n = 52). We statistically compared the concentration of each contaminant in case associated, noncase-associated, and control samples of each sample set. The analyses showed that there were more than 60 minor contaminants in the LT from Showa Denko K.K., and that six of these contaminants were associated with EMS. The structures of three contaminants are known, but the identities of the other three contaminants are currently unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346974 TI - The effect of salinity on the acute toxicity of cadmium to the tropical, estuarine, hermaphroditic fish, Rivulus marmoratus: a comparison of Cd, Cu, and Zn tolerance with Fundulus heteroclitus. AB - The mangrove-dwelling fish, Rivulus marmoratus, is the only vertebrate that is a synchronous, internally self-fertilizing hermaphrodite. This unique reproductive mode yields offspring with little genetic variation, which offers significant advantages for the use of this species in bioassays. We conducted acute (96 h) LC50 tests of Cd toxicity under four different water chemistry conditions, representing fresh water (low [Ca+Mg] and low [Na+K]), 14 ppt sea water simulated with Cl salts (high [Ca+Mg] and high [Na+K]) and two artificial conditions (high [Ca+Mg], low [Na+K] and low [Ca+Mg], high [Na+K]). Two replicates were conducted at different times for each of the four treatments and the results were very reproducible. The mean LC50's as mg total Cd/L were 2.96 (fresh water), 21.12 (high [Ca+Mg], high [Na+K]), 17.86 (high [Ca+Mg], low [Na+K]) and 12.67 (low [Ca+Mg], high [Na+K]). An additional test in 14 ppt sea water (made up from Instant Ocean salts) yielded a 96h LC50 of 24.48 mg Cd/L, and was thus similar to the high [Ca+Mg]-high [Na+K] treatment, despite some differences in anion and cation concentrations. The degree to which [Ca+Mg], [Na+K] and [Cl] interact to determine Cd toxicity is still unclear, although the role of [Cl] is likely to be equal to or greater than that of [Ca+Mg]. When all solutes are high, it is likely that the formation of a Cd complex with Cl (248 mM) leads to the observed reduction in Cd toxicity in comparison with hard fresh water, not the increased divalent [Ca+Mg] levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346975 TI - Recent developments in the understanding of paediatric musculoskeletal pain syndromes. PMID- 8346976 TI - Joint hypermobility and fibromyalgia in schoolchildren. AB - OBJECTIVES: To test the hypothesis that joint hypermobility may play a part in the pathogenesis of pain in fibromyalgia, schoolchildren were examined for the coexistence of joint hypermobility and fibromyalgia. METHODS: The study group consisted of 338 children (179 boys, 159 girls; mean age 11.5 years, range 9-15 years) from one public school in Beer-Sheva, Israel. In the assessment of joint hypermobility, the criteria devised by Carter and Bird were used. Any child who met at least three of five criteria was considered to have joint hypermobility. Children were considered to have fibromyalgia if they fulfilled the 1990 American College of Rheumatology criteria for the diagnosis of fibromyalgia, namely, widespread pain in combination with tenderness of 11 or more of the 18 specific tender point sites. The blind assessments of joint hypermobility (by AG) and fibromyalgia (by DB) were carried out independently. RESULTS: Of the 338 children 43 (13%) were found to have joint hypermobility and 21 (6%) fibromyalgia; 17 (81%) of the 21 with fibromyalgia had joint hypermobility and 17 (40%) of the 43 with joint hypermobility had fibromyalgia. Using chi 2 statistical analysis, joint hypermobility and fibromyalgia were found to be highly associated. CONCLUSIONS: This study suggests that there is a strong association between joint hypermobility and fibromyalgia in schoolchildren. It is possible that joint hypermobility may play a part in the pathogenesis of pain in fibromyalgia. More studies are needed to establish the clinical significance of this observation. PMID- 8346977 TI - Self report functional disability scores and the use of devices: two distinct aspects of physical function in rheumatoid arthritis. AB - OBJECTIVES: Self report scores of physical disability and the use of devices or assistance in performing activities are sometimes integrated in one index of physical function, although they are aimed at measuring different dimensions of physical disability. The properties of both parameters were evaluated in two groups of patients with rheumatoid arthritis (RA). METHODS: A group of patients with RA of recent onset was compared with a group with established disease on four parameters of disability: use of devices, use of personal assistance, and scores on a validated Dutch version of the Health Assessment Questionnaire Disability Index, with and without integrating the use of devices or assistance. Correlation coefficients among disability parameters were calculated. In multiple regression analysis the influence of disease duration on the disability parameters was determined after disease activity, psychological wellbeing, and demographical characteristics had been controlled. RESULTS: Functional disability scores were mainly related to inflammatory activity and psychological wellbeing, whereas the uses of devices had a strong relation with disease duration, independent of current disease activity. Integrating these parameters of disability yielded a parameter that was still mainly associated with disease activity. CONCLUSION: Self report scores of functional disability and the use of devices represent distinct dimensions of physical function in RA. Integrating both parameters into one measure of physical disability does not provide an index adequately reflecting both dimensions. The use of both parameters to measure outcome in long term clinical studies is recommended. PMID- 8346978 TI - Small intestinal bacterial overgrowth in patients with rheumatoid arthritis. AB - OBJECTIVES: To examine the microflora of the upper small intestine in patients with seropositive rheumatoid arthritis (RA) using a combination of microbial cultivation and tests for microbial metabolic activity. METHODS: Twenty five patients with seropositive RA, 12 achlorhydric control subjects, and 11 control subjects with normal gastric acid secretion were investigated. Disease activity was evaluated in the patients with RA by three different indices. Eight (32%) of the patients with RA had hypochlorhydria or achlorhydria. The acid secretory capacity was determined with pentagastrin stimulation. A modified Crosby capsule was used to obtain biopsy specimens and samples of intestinal fluid from the proximal jejunum; aerobic and anaerobic microbial cultivation of mucosal specimens/intestinal fluid was carried out, and gas production and microflora associated characteristics in jejunal fluid were determined. Additionally, a bile acid deconjugation breath test was performed. RESULTS: Subjects with at least one of the following findings were considered to have bacterial overgrowth: positive bile acid deconjugation test; growth of Enterobacteriaceae; positive gas production; or low tryptic activity. By these criteria half of the patients with RA with hypochlorhydria or achlorhydria and half of the achlorhydric controls had bacterial overgrowth. Thirty five per cent of the patients with RA with normal gastric acid secretion had bacterial overgrowth compared with none of the normal controls. Disease activity indices and rheumatoid factor titres were significantly higher in patients with RA with bacterial overgrowth than in those without. CONCLUSIONS: A high frequency of small intestinal bacterial overgrowth was found in patients with RA; it was associated with a high disease activity and observed in patients with hypochlorhydria or achlorhydria and in those with normal acid secretion. PMID- 8346979 TI - Radiographic patterns and associations of osteoarthritis of the knee in patients referred to hospital. AB - OBJECTIVES: To investigate differing patterns and associations of osteoarthritis of the knee in patients referred to hospital. METHODS: Two hundred and fifty two consecutive patients (161 women, 91 men; mean age 70 years, range 34-91 years) referred to hospital with osteoarthritis of the knee underwent clinical, radiographic, and synovial fluid screening. RESULTS: Radiographic changes of osteoarthritis of the knee (definite narrowing with or without osteoarthritic features) were bilateral in 85% of patients. Of 470 knees affected, 277 (59%) were affected in two compartments and 28 (6%) in three compartments. Unilateral and isolated medial tibiofemoral osteoarthritis were more common in men. Calcium pyrophosphate crystal deposition was common (synovial fluid identification in 132 (28%) knees; knee chondrocalcinosis in 76 (30%) patients) and associated with disability, bilateral, multicompartmental and severe radiographic osteoarthritis, marked osteophytosis, attrition, and cysts. Multiple clinical nodes (58 (23%) patients) and radiographic polyarticular interphalangeal osteoarthritis (66 (26%) patients) were associated with a higher frequency of inactivity pain, disability, multicompartmental and severe radiographic change. Forestier's disease predominated in men but showed no other associations. CONCLUSIONS: In a group of patients referred to hospital osteoarthritis of the knee is usually bilateral and affects more than one compartment. Severe and multicompartmental radiographic changes are associated with calcium pyrophosphate crystal deposition, nodal change, and polyarticular interphalangeal osteoarthritis. PMID- 8346981 TI - Scleroderma and malignancy: an epidemiological study. AB - OBJECTIVES: Although case reports and some patient series suggest an increased risk of cancer among patients with scleroderma, there are no population based studies to support this association. A population based follow up study was therefore carried out of 233 patients with scleroderma from the six-county Uppsala health care region of Sweden for the time period 1955-84. METHODS: Using the inpatient registry for the Uppsala health care region, all patients with scleroderma were identified. Their unique identification codes were then used to perform a record linkage with the National Cancer Registry. Expected cancer rates were determined using the age and gender specific rates for the Uppsala health care region. RESULTS: The standardised incidence ratio (SIR) for all cancers among these patients was significantly increased (SIR = 2.4; 95% CI = 1.5 to 3.6). The SIRs for lung cancer (SIR = 7.8; 95% CI = 2.5 to 18.2) and non Hodgkin's lymphoma (SIR = 9.6; 95% CI = 1.1 to 34.5) were also significantly increased. Excluding patients who were diagnosed with cancer within a year of their scleroderma diagnosis resulted in similar findings, though the SIR for non Hodgkin's lymphoma was no longer statistically significant. CONCLUSIONS: Larger population based investigations of cancer risk among patients with scleroderma are needed to confirm these initial findings and to evaluate in greater detail possible cancer risk among these patients. PMID- 8346980 TI - Various rheumatic syndromes in adult patients associated with high antistreptolysin O titres and their differential diagnosis with rheumatic fever. AB - OBJECTIVES: The purpose of this study was to analyse retrospectively adult patients with acute joint or muscle symptoms and a high antistreptolysin O (ASO) titre to find out which syndromes of clinical arthritis are associated with serological evidence of streptococcal infection. METHODS: Seventy six adult patients with an acute arthritis syndrome or an exacerbation in their chronic rheumatic disease and simultaneously a high ASO titre (> or = 500 Todd units) were examined in two time periods in the 1980s. RESULTS: Twenty six patients had arthritis associated with a known rheumatic disease, 25 had non-specific arthralgia/myalgia, 20 had reactive arthritis, and five had septic arthritis. No case of classic rheumatic fever classified by two major criteria was found. Six patients fulfilled one major and at least two minor criteria. The frequency of HLA-B27 was significantly higher in the whole patient group than in the healthy Finnish population (30 v 14%). CONCLUSIONS: It is concluded that classic rheumatic fever is now rare, even in patients with arthritis with a high ASO titre. These results support the suggestion that beta haemolytic streptococci may trigger reactive arthritis as well as rheumatic fever. PMID- 8346982 TI - Absence of an association between HLA-DRB1*04 and rheumatoid arthritis in newly diagnosed cases from the community. AB - OBJECTIVES: To determine HLA-DR4 and DR1 allele frequencies in a series of patients with newly diagnosed early inflammatory arthritis. METHODS: HLA-DR1 and DR4 frequencies were determined by oligonucleotide typing of 208 patients classified as having either rheumatoid arthritis (RA) or undifferentiated inflammatory polyarthritis. RESULTS: The frequency of occurrence of DR4 in these patients with RA did not differ significantly from that in controls in the United Kingdom (42 v 37%). HLA-DR1 was increased in the group with inflammatory polyarthritis (25 v 18%). CONCLUSIONS: The frequency of DR4 is not increased in newly diagnosed community based patients with RA. This supports the hypothesis that DR4 is less important as a marker for susceptibility to RA than it is for disease persistence or severity. PMID- 8346984 TI - Clinical evolution of sacral stress fractures: influence of additional pelvic fractures. AB - OBJECTIVES: To evaluate the clinical evolution of sacral stress fractures in relation to the scintigraphic pattern and the presence of additional pelvic fractures. METHODS: This was a retrospective study of 14 patients with sacral fractures. RESULTS: Six patients had additional pelvic fractures. Four bone scintigraphic patterns were found. The resolution of symptoms was longer in patients with associated pelvic fractures (30 weeks v three weeks). No relation was found between the bone scintigraphic pattern and the time of evolution. CONCLUSION: Associated pelvic fractures delay the resolution of symptoms in patients with sacral fractures, regardless of scintigraphic pattern. PMID- 8346983 TI - Lack of association of increased antibody levels to mycobacterial hsp65 with rheumatoid arthritis: results from a study of disease discordant twin pairs. AB - OBJECTIVES: To investigate the role of humoral immunity to mycobacterial hsp65 in the aetiology of rheumatoid arthritis. METHODS: Levels of IgG antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples of 152 twin pairs discordant for RA and in serum samples from 62 normal blood donors. RESULTS: No significant differences between antibody levels in the subjects with RA compared either with their unaffected twins or with a group of normal blood donors was observed. In the monozygotic twins there was a strong but negative association between levels of antibody to hsp65 and disease status. Zygosity, sex, and HLA status did not significantly affect levels of antibody to hsp65. CONCLUSION: Previous reports of an association between hsp65 and RA were not confirmed. PMID- 8346985 TI - Long term follow up of radiosynovectomy with yttrium-90 silicate in haemophilic haemarthrosis. AB - OBJECTIVES: The aim of this study was to evaluate the long term effect of radiation synovectomy with yttrium-90 silicate in haemophiliac patients with recurrent haemarthrosis. METHODS: The bleeding frequency and the mobility of the joint were recorded in 16 joints of 14 patients 1 year before radiosynovectomy and during follow up, which ranged from 3 to 6 years. Patients evaluated the effect of their own treatment by completing a questionnaire. Radiographs of the joints were scored by an independent radiologist before treatment. RESULTS: A satisfactory reduction of the frequency of haemorrhage was achieved in 94% of joints during the first year after treatment and was maintained in 63% until the end of the follow up period. In general there was no decrease in mobility attributable to radiosynovectomy, and the patients' own evaluations agreed with the evaluations based on the frequencies of haemarthrosis in 75%. Patients who had only minor, or no, radiological abnormalities of the joints before treatment showed the best results. One patient developed synovitis as a complication of the radiosynovectomy. CONCLUSION: Radiosynovectomy is an effective and safe treatment for recurrent haemarthrosis in haemophiliac patients, especially in those who have joints with no or minor radiological damage. PMID- 8346986 TI - Visceral leishmaniasis. PMID- 8346987 TI - The chemotherapy of rodent malaria. XLVIII. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 1: Studies leading to the development of novel cis-fused cyclopenteno derivatives. AB - The new Chinese antimalarial blood schizontocide, artemisinin, derived from the plant Artemisia annua, displays a high level of activity against polyresistant Plasmodium falciparum. Several synthetic 1,2,4-trioxanes were examined in a search for compounds that exhibit a similar type of action against drug-resistant parasites. This paper, the first of a series, describes the examination of these trioxanes against drug-sensitive and drug-resistant malaria parasites in a rodent model, using artemisinin and arteether as comparison standards. Cis-fused cyclohexeno-1,2,4-trioxanes (10-17) substituted with various side-chains revealed for the most part variable but weak antimalarial activity. On the other hand, cis fused cyclopenteno-1,2,4-trioxanes (18-19) showed greater activity, 19 showing about 1/30th of the activity of arteether against drug-sensitive Plasmodium berghei in vivo, thereby providing a clue to the structure-activity relationship. PMID- 8346988 TI - Increased circulating levels of transcobalamin II in malarial patients with renal involvement. AB - Vitamin B12 and its binding proteins were measured in the serum and urine of four patients with Plasmodium falciparum who had renal insufficiency. The results showed that these patients had elevated serum transcobalamin II (TCII) levels which decreased to the normal level after recovery from azotaemia. There were direct relationships between serum TCII levels and blood urea-nitrogen or creatinine concentrations. The clearance and urinary excretion of vitamin B12 and TCII were significantly lower in the patients' group than in normal subjects. All these findings indicated that elevated serum TCII could occur in P. falciparum patients with renal insufficiency. This is probably caused by a reduction in renal plasma flow and glomerular filtration rate (GFR), secondary to a low or ineffective blood volume. The reduced GFR, in turn, reduces the TCII-B12 that filters through the glomeruli, resulting in decreased TCII-B12 uptake by the renal tubules, and thus slows down the TCII degradation by lysosomal enzymes. The decreased TCII catabolism therefore prolongs the TCII survival in the circulation and probably stimulates TCII synthesis and secretion in a feedback mechanism. PMID- 8346989 TI - Thermotherapy v. antimonials: what happens after the healing of cutaneous leishmaniasis lesions? AB - The long-term effects of meglumine antimoniate (chemotherapy) or exposure to an environmental temperature of 37 degrees C (thermotherapy) on the evolution of Leishmania mexicana infections and on the response to challenge infections six months after treatment were compared in susceptible (BALB/c) and partially resistant (C57BL/6) mice. Thermotherapy was better than chemotherapy in that it healed lesions quicker and prevented relapses in the partially resistant mice during the observation period. However, both treatments appeared equally effective in terms of clinical cure. Neither treatment cleared all parasites from the hosts and both impaired the hosts' immune response to a challenge infection. The results indicate that specific immunity fades with time post-infection and that the persistence of the parasite in a clinically cured host does not maintain protective immunity against challenge infections. PMID- 8346990 TI - Entamoeba histolytica: antibody response to recent and past invasive events. AB - Sero-epidemiological data from endemic amoebiasis areas are difficult to evaluate because the serology of individuals affected by an active process of Entamoeba histolytica tissue invasion is, at present, almost impossible to distinguish from that of individuals who have had an invasive event in the past. The present study compares serum antigenic recognition frequencies among three groups of individuals with different infective conditions: amoebic liver abscess patients; asymptomatic cyst passers; and individuals who have had amoebic liver abscess from one to three years before the study. Control groups consisted of Mexican and Canadian healthy adults. Western blots of E. histolytica membrane extract antigen were reacted with sera from the studied individuals, recognition frequency values were calculated and immunoplots of frequency differences were constructed. The results obtained suggest that the identification and purification of antigenic fractions, which are frequently recognized by sera of amoebic liver abscess patients (136, 132, 93, 70 and 62 kDa), or preferentially associated with past invasive events (144, 140 and 49 kDa), or related to the E. histolytica cyst passer condition (62 and 136 kDa), are important improvements in the use of serology for diagnosis and epidemiological studies in endemic areas of amoebiasis. PMID- 8346991 TI - Description of a computer model of forest onchocerciasis transmission and its application to field scenarios of vector control and chemotherapy. AB - This paper describes a computer simulation model for onchocerciasis (SIMON). Using epidemiological and entomological data from a specific hyperendemic village in the forest area of Sierra Leone, the model is used to examine the effect of vector and chemotherapeutic control strategies, both separately and in combination, as well as the risk to an uninfected population caused by immigrant, infected Simulium damnosum and humans. The model suggests that, in this village, the human population of about 420 requires an average annual input of about 200 mature fecund, female Onchocerca volvulus per year to maintain a skin-snip prevalence of just under 70%. SIMON also predicts that 99% effective vector control would lead to eradication of all adult worms in 18 years, and that abandoning control before 14 years could lead to recrudescence. Chemotherapy with ivermectin at six-month intervals reaching 90% of eligible persons (effective 66%) might take 29 years to achieve eradication because of continuing transmission, particularly in the early years, but it would probably be possible to abandon treatments after 18 years because the residual worm population would no longer be self-sustaining. Combined ivermectin and vector control, both at reduced levels, could be as effective as 99% vector control. Immigrant infected flies are likely to pose a greater threat to an uninfected human population than small numbers of infected persons. The model suggests that, at levels of infection undetectable by skin-snip, the parasite could linger in the human population for 30 or more years sustained by sporadic transmission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346992 TI - Multivariate morphotaxonomy in the identification of adult females of the Simulium damnosum Theobald complex (Diptera: Simuliidae) in the Onchocerciasis Control Programme area of West Africa. AB - Adult female Simulium damnosum s.l. flies obtained in nine countries of the Onchocerciasis Control Programme were examined for 14 morphological characters with the aim of selecting specific characters to identify the main species that form the complex. Two approaches were used, the first involved discriminant function analysis of the species groups using all the characters which were both qualitative (the colour of the fore coxa, the antennae, the wing tuft, the arculus, the ninth abdominal tergite setae and the scutellar setae) and quantitative (the lengths of thorax, antenna, and femur, tibia and first basitarsus of both the fore and hind legs) in nature. The second sought colour characters unique to the S. damnosum subcomplex and to S. yahense, to separate them from the rest, and progressively applied discriminant analyses in the dichotomous stepwise manner to within the subcomplex level. The combination of pale arculus and pale antennae with pale or dark fore coxae were unique to the S. damnosum subcomplex, whilst those of black arculus together with wholly dark or mixed ninth abdominal tergite setae and scutellar setae were unique to S. yahense. Further discrimination was achieved between subcomplexes and species by entering the qualitative and quantitative characters into discriminant function analysis. The two schemes were both successful at separating the main species subcomplexes of the S. damnosum complex, with 90-100% correct classification. Within the subcomplex level, correct identification of sibling species was 85 100% successful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8346993 TI - Check list and geographical distribution of phlebotomine sandflies in China. AB - A total of 42 species of sandflies, included in five genera, have been recorded from 31 of 32 provinces, municipalities and autonomous regions of China (excluding Heilongjiang Province). Five species, namely Phlebotomus alexandri, P. chinensis, P. longiductus, P. sichuanensis and P. smirnovi (syn. P. wui), are known to be vectors of human leishmaniasis. A list of these 42 phlebotomines is given, and their geographical distributions in China are described. PMID- 8346994 TI - The chemotherapy of rodent malaria. XLIX. The activities of some synthetic 1,2,4 trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 2: Structure-activity studies on cis-fused cyclopenteno-1,2,4-trioxanes (fenozans) against drug-sensitive and drug-resistant lines of Plasmodium berghei and P. yoelii ssp. NS in vivo. AB - The activity of 51 synthetic cis-fused cyclopenteno-1,2,4-trioxanes has been examined against drug-sensitive and chloroquine-resistant malaria parasites in vivo. Some of them display high levels of blood schizontocidal activity when administered orally or subcutaneously. They retain their activity against lines of parasites that are resistant to widely differing antimalarials such as 4 aminoquinolines, aminoalcohols, dihydrofolate reductase inhibitors and artemisinin. The most potent compound of the present series is cis-(+/-)-4a,7a dihydro-6,7a-di(p-fluorophenyl)spiro [cyclopentane-3,3'-7H-cyclopenta-1,2,4 trioxin], otherwise known as Fenozan-50F. PMID- 8346995 TI - Development of Theileria sergenti in vector ticks, Haemaphysalis longicornis, during blood sucking. PMID- 8346996 TI - Comparative evaluation of five diagnostic methods for demonstrating microsporidia in stool and intestinal biopsy specimens. PMID- 8346997 TI - Halfway technology takes another step forward. PMID- 8346998 TI - Electrical therapy of ventricular arrhythmias: the surgeon's approach. PMID- 8346999 TI - Heart-lung transplantation: consensus, experience, or both? PMID- 8347000 TI - Isolated single-lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection. AB - To investigate new modalities in the treatment of pulmonary metastases we developed a model of isolated single-lung perfusion in the rat. In this study we compare the pharmacokinetics of isolated lung perfusion and intravenous doxorubicin. In the first experiment, designed to evaluate lung tissue levels of doxorubicin, 35 rats were randomized into seven groups (n = 5). The first five groups underwent isolated lung perfusion with 72.1 +/- 6.9, 118.4 +/- 12.1, 255.2 +/- 12.8, 384.1 +/- 46.2, and 457.6 +/- 32.5 micrograms/mL of doxorubicin, respectively, for 10 minutes. Groups 6 and 7 received 5 mg/kg and 7 mg/kg of intravenous doxorubicin, respectively. A second study was designed to measure heart tissue level of doxorubicin in 3 groups of 5 rats each. Two groups received 5 or 7 mg/kg of intravenous doxorubicin and a third group underwent isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL of doxorubicin for 10 minutes. A third study, designed to evaluate toxicity in vivo, had a similar design, and the animals were followed up for 21 days after treatment. Lung doxorubicin concentration after isolated lung perfusion was significantly higher than after intravenous doxorubicin (p < 0.01). Tissue doxorubicin concentration was 25 and 20 times higher after isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL than after 5 or 7 mg/kg of intravenous doxorubicin, respectively. Heart concentration of doxorubicin was significantly lower after isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL of doxorubicin as compared with 5 or 7 mg/kg of intravenous doxorubicin (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347001 TI - Effects of triiodothyronine supplementation after myocardial ischemia. AB - Cardiopulmonary bypass causes a "euthyroid-sick" state characterized by low levels of circulating triiodothyronine. Triiodothyronine supplementation in this setting has been postulated to improve postischemic left ventricular function by increasing the availability of myocardial high-energy phosphates. These postulates have not been substantiated, however, using load-independent parameters of left ventricular function and analysis of high-energy phosphate metabolism. To test these hypotheses, 14 healthy pigs (30 to 40 kg) were placed on cardiopulmonary bypass and instrumented with left ventricular minor-axis ultrasonic crystals and micromanometer-tipped pressure catheters. Hearts were subjected to 30 minutes of global, normothermic ischemia. Triiodothyronine (0.1 mg/kg; n = 7) or placebo (n = 7) was administered in a random, investigator blinded fashion at the removal of the aortic cross-clamp and after 60 minutes of reperfusion. Hemodynamic, metabolic, and ultrastructural data were obtained before ischemia and after 30, 60, 90, and 120 minutes of reperfusion. By 90 minutes of reperfusion left ventricular contractility had returned to preischemic levels in hearts supplemented with triiodothyronine, despite postischemic myocardial adenosine triphosphate levels of 50% to 60% of baseline in both groups. Ultrastructurally, the sarcoplasmic reticulum and mitochondria were significantly better preserved in the group treated with triiodothyronine. This study suggests that triiodothyronine supplementation significantly enhances postischemic left ventricular functional recovery and that this recovery is due to mechanisms other than enhanced availability of myocardial high-energy phosphates. PMID- 8347002 TI - Thromboembolism in patients undergoing thoracotomy. AB - To determine the incidence of thromboembolism in relation to thoracotomy, 77 patients undergoing pulmonary resection were prospectively studied up to 30 days postoperatively for deep venous thrombosis and pulmonary embolism. Overall, 20 of 77 patients (26%) had thromboembolic events during their hospitalization. Four deep venous thromboses and 1 pulmonary embolism were detected in 5 of 77 patients preoperatively for an incidence of 6%. Postoperative thromboembolism was detected in 15 of 77 (19%): deep venous thrombosis in 11 (14%) and pulmonary embolism in 4 (5%). No postoperative thromboembolisms occurred in the 17 patients receiving preoperative aspirin or ibuprofen, whereas they did occur in 25% of the remainder (15/60). Thromboembolism after pulmonary resection was more frequent with bronchogenic carcinoma than with metastatic cancer or benign disease (15/59 [25%] versus 0/18 [0%]; p < 0.01), adenocarcinoma compared with other types of carcinoma (11/25 [44%] versus 4/34 [12%]; p < 0.0004), large primary lung cancer (> 3 cm in diameter) compared with smaller lesions (9/19 [47%] versus 6/40 [15%]; p < 0.0001), stage II compared with stage I (7/14 [50%] versus 7/34 [21%]; p < 0.04), and pneumonectomy or lobectomy compared with segmentectomy and wedge resection (14/49 [29%] versus 1/28 [4%]; p < 0.005). Three of 4 patients with thromboembolism detected preoperatively had operation within the previous year. Postoperative pulmonary embolism was fatal in 1 of 4 (25%) and accounted for the one death. These results suggest patients undergoing thoracotomy for lung cancer, especially adenocarcinoma, should be considered for thromboembolic prophylaxis. PMID- 8347003 TI - Replacement of the aortic valve with cryopreserved aortic allograft. AB - Replacement of the aortic valve with cryopreserved aortic allograft was performed in 88 patients during the period from July 1985 until January 1993. Age of patients ranged from 15 to 75 years (mean, 44 years). The cause of aortic valve disease was congenital in 39 (44%), rheumatic in 9 (10%), degenerative in 14 (16%), endocarditis in 11 (13%), and failed prosthesis in 15 (17%). The operation was performed by freehand allograft technique in 71 patients (81%). There were no perioperative deaths. Two patients died later at 4 months and 5 years after operation (actuarial survival = 94% at 7.5 years). Follow-up extending to 7.5 years shows 87% of patients are in New York Heart Association functional class I. No thromboembolism has been detected in any patient. Infection was cured in all patients with endocarditis. Mild aortic valve incompetence was detected by diastolic murmur in 45% of patients. Only three valves have been removed at reoperation: one was removed early for technical reasons, and two valves were removed for structural degeneration at 33 and 55 months; the latter was infected. Actuarial freedom from reoperation for any reason was 89%; for structural deterioration it was 93% at 7.5 years. Aortic valve replacement with cryopreserved aortic allograft can be safely performed in adult patients. Medium term results show excellent freedom from thromboembolism and cure of bacterial endocarditis. Mild aortic valve incompetence is often present, but reoperation for progressive incompetence is unusual. PMID- 8347004 TI - Endothelial cell replication in an in vivo model of aortic allografts. AB - Previous studies of aortic valve allograft viability have used in vitro assessments that may not reflect in vivo properties. This study evaluated in vivo endothelial cell replication in experimental valved aortic grafts and examined the consequences of histoincompatibility and cryopreservation. Valved aortic conduits were heterotopically transplanted into syngeneic or allogeneic rats. Tritiated thymidine was administered to graft recipients and control rats. After 72 hours, monolayers from the native aortas and the aortic portion of the grafts were prepared for autoradiography, with six or more silver grains per nucleus considered evidence of replication. Percentages of replicating cells in native aortas ranged from 0.3% to 2.3% (p = not significant). Percentages of replicating cells in the fresh isografts (12.4%) and allografts (12.2%) were not significantly different from each other, although each was significantly greater than the percentage in its native aorta (p < 0.04). Cryopreserved allografts and isografts displayed a few endothelial cells, none of which was replicating. Immunologic differences do not affect endothelial cell replication in this early period after fresh graft transplantation. Cryopreservation, however, results in the absence of replicating endothelium. PMID- 8347005 TI - Linear left ventricular aneurysmectomy: modern imaging studies reveal improved morphology and function. AB - It remains uncertain whether left ventricular aneurysmectomy (LVA) improves ventricular function and whether LVA improves or distorts left ventricular contour. We applied the powerful imaging techniques of multiple-gated acquisition scanning, intraoperative transesophageal echocardiography, and magnetic resonance imaging to assess functional and morphologic changes after LVA in 75 consecutive patients undergoing LVA by conventional resection and linear closure. Fifty-two patients (69%) underwent concomitant coronary artery bypass grafting, 25 (33%) had directed endocardial resection, and 4 (5%) had valve replacement. The hospital mortality rate was 6.7% (5/75). Actuarial survival rates were 86%, 80%, and 64% at 1 year, 2 years, and 5 years, respectively. Mean anginal class improved from 3.49 to 1.24 (p < 0.0001). Mean congestive heart failure class improved from 3.04 to 1.70 (p < 0.0001). By multiple-gated acquisition scan (48 patients), mean ejection fraction improved from 0.25 preoperatively to 0.33 postoperatively (p < 0.0001). Intraoperative transesophageal echocardiography (28 patients) revealed no cases of distortion and demonstrated normalization of left ventricular contour in 69% of patients. Mean wall motion score improved from 16.4 to 18.8 (p < 0.001). Mean cross-sectional area of the left ventricle decreased from 18.7 cm2 to 12.8 cm2 (p < 0.006). Magnetic resonance imaging confirmed normalization of left ventricular contour without distortion. We conclude that linear LVA is clinically effective and objectively improves left ventricular morphology and function. On this basis, we have extended application of LVA to include patients with at least moderate-sized aneurysms undergoing coronary artery bypass grafting, despite the absence of traditional indications of arrhythmia, embolism, and frank congestive heart failure. PMID- 8347006 TI - Pulmonary arteriovenous malformations: therapeutic options. AB - We have treated 21 patients (13 female, 8 male) with pulmonary arteriovenous malformations (PAVMs). Mean age at diagnosis was 37.5 years (range, 15 to 72 years). Presenting symptoms included dyspnea on exertion (67%), hereditary hemorrhagic telangiectasia (57%), and major neurologic events (33%). In our early experience, 8 patients had no specific treatment; their case histories illustrate the major neurologic complications of untreated PAVMs. Nine patients (8 primarily, 1 after recurrence) underwent conservative surgical excision; 4 had lobectomy, and 5 had segmentectomy or subsegmental excision. One patient underwent staged bilateral thoracotomies for multiple bilateral lesions. The arterial oxygen tension was found to increase after excision of large or solitary PAVMs. All surgically treated patients were relieved of dyspnea, and none had postoperative recurrence of PAVMs or neurologic complications related to PAVMs. Five patients underwent balloon occlusion of PAVMs. Two patients chose to have solitary PAVMs occluded rather than undergo thoracotomy. One underwent surgical excision 5 years later, and the other required repeat balloon embolization 4 years later when recanalization of the PAVMs was documented. Three patients with numerous PAVMs received palliation with multiple balloon embolizations. The high incidence of associated major neurologic complications mandates aggressive treatment of PAVMs whenever feasible. Conservative surgical resection remains the treatment of choice. Balloon embolization offers an alternative therapy for patients who are poor surgical risks or those whose lesions are too numerous to resect. PMID- 8347007 TI - Reoperations after operation on the thoracic aorta: etiology, surgical techniques, and prevention. AB - Recurrent aortic aneurysms, persistent or new dissection, new onset of valvular and coronary artery disease, graft infection, and prosthetic endocarditis are not rare after thoracic aortic operations; they can be difficult to diagnose and represent a formidable surgical challenge. Between 1977 and 1991, 876 operations were performed on the thoracic aorta in our institution: 340 in dissections, 299 in true aneurysms, 150 for aortic remodeling and external wall support during aortic valve replacement, and 87 for miscellaneous causes. During the same period, there were 193 additional reoperations. Vascular reoperations on abdominal aorta and peripheral arteries accounted for 73 cases and are not further discussed in this study. The reasons for reoperation (n = 130) in 120 patients were: failure of biologic valves (n = 23); aneurysm recurrence in a proximal or distal aortic segment (n = 21); pseudoaneurysm formation at suture lines (n = 13); new dissection or dilatation involving ascending aorta (n = 11), aortic arch (n = 13), and descending aorta (n = 10); aneurysm after aortic remodeling (n = 13); new onset of valvular disease (n = 5); and new onset of coronary disease (n = 5). Infected aortic graft and prosthetic endocarditis accounted for 10 reoperations, and a planned two-staged procedure was performed in 6 patients. Omitting the failed biologic valves, reoperations were performed on the aortic segment previously operated on in 69.3% of the cases and on other thoracic segments in 30.7%. Overall hospital mortality rate after reoperation was 5.8%. A significant decrease in operative mortality was observed in the most recent period (3.0% between 1989 and 1991). Reoperations are technically demanding, and some of them are preventable; therefore (1) graft inclusion technique should be abandoned in ascending aortic operation due to formation of false aneurysms; (2) in patients with Marfan syndrome, complete repair of the diseased aorta should be attempted during the initial operation; (3) aortic arch dissection should be repaired definitively during the first operation in low-risk patients; (4) biological valves should be avoided in aneurysm operations; and (5) homograft replacement is the treatment of choice in prosthetic endocarditis or in infected composite graft after an aortic valve or ascending aortic operation. PMID- 8347008 TI - Brain protection via cerebral retrograde perfusion during aortic arch aneurysm repair. AB - Eleven patients underwent resection and graft replacement of ascending and aortic arch aneurysms. Retrograde cerebral perfusion was used during the procedures to minimize cerebral ischemia. Retrograde cerebral perfusion (15 degrees to 24 degrees C) was administered through the superior vena cava. The mean cerebral ischemic time was .35 minutes (range, 11 to 71 minutes). Throughout retrograde cerebral perfusion, blood samples were drawn from the innominate and left carotid arteries at 1, 5, and every 10 minutes thereafter for analysis of arterial oxygen content, total creatine kinase level, and creatine kinase BB fraction. All patients survived. All except 1 awoke neurologically intact. In this patient, electroencephalogram and transcranial Doppler studies conducted before circulatory arrest were consistent with embolic phenomena. There was no significant difference between the current group's intraoperative electroencephalograms and those of a similar historical group. Postoperative complications included transient renal failure, myasthenia gravis, cholecystitis, premature atrial contractions, atrial fibrillation, and vocal cord paralysis. The creatine kinase BB fraction range was 1.8 to 13.4. The increase of total creatine kinase level was due to MM fraction. Retrograde cerebral perfusion during circulatory arrest is a valuable adjunct for protecting the brain. The creatine kinase BB band was not a good marker to detect brain injury. With continued use of this technique and accumulation of a larger series, we may better define the role of retrograde cerebral perfusion in brain protection. PMID- 8347009 TI - Failure of the Hemashield extension in right ventricle-to-pulmonary artery conduits. AB - Between 1989 and 1991, 17 children underwent 18 right ventricle-to-pulmonary artery conduit placement operations using a composite of an aortic or pulmonary valved homograft and a Hemashield extension to the ventricle. Hemashield is a collagen-coated knitted Dacron graft with excellent compliance and hemostatic properties. Diagnoses included tetralogy of Fallot with pulmonary atresia (7), truncus arteriosus (6), and complex transposition of the great arteries (4). Mean age at conduit placement was 4.9 +/- 4.2 years, and all patients survived. At a mean follow-up of 14 +/- 4 months, postoperative Doppler echocardiographic gradients between the ventricle and pulmonary artery ranged from less than 20 to 60 mm Hg. At cardiac catheterization 13 +/- 3 months postoperatively (6 patients), the systolic pressure gradient across the conduits ranged from 14 to 90 mm Hg (mean gradient, 59 +/- 29 mm Hg). Conduit obstruction, when present, was demonstrated angiographically to be in the Hemashield portion and led to early conduit replacement six times in 5 patients (33% of operations) within 10 to 18 months (mean time, 14 months) after insertion of the original conduit. Pathologic examination of the explanted conduits revealed the obstruction to be a thick neointimal peel that was impossible to separate from the Hemashield graft. Failure of the Hemashield as an extension for ventricle-to-pulmonary artery conduits secondary to accelerated neointimal formation has led us to abandon its use in clinical practice. PMID- 8347010 TI - Preliminary results with neoadjuvant therapy and resection for esophageal carcinoma. AB - Between December 1988 and August 1992, 68 patients with adenocarcinoma (n = 39) and squamous carcinoma (n = 29) of the esophagus were entered prospectively in a treatment protocol to receive two cycles of cisplatin, 5-fluorouracil, etoposide, leucovorin, and 3,000 cGy of radiation to the involved esophagus and adjacent mediastinum, followed by resection. There were four deaths during chemotherapy, and 7 patients had a decline in condition or were denied operation. Fifty-six patients have come to operation, and 1 awaits resection. Twenty-two patients had transhiatal esophagectomy and 29 patients had esophagogastrostomy with a combined abdominal and right thoracic approach. Five patients did not undergo resection at operation. There was one hospital death (2%). A complete response to preoperative therapy was seen in 12 patients (21%): 5 of 20 with squamous cancer (25%) and 7 of 36 with adenocarcinoma (19%). Average follow-up is 19 months. Median survival in these patients after entrance in the protocol is 24 months. Actuarial survival at 12, 18, and 24 months is 72% (confidence limits, 66% and 78%), 53% (confidence limits, 46% and 60%), and 51% (confidence limits, 44% and 58%). Significantly better survival was associated with adenocarcinoma (p = 0.041). There is no survival advantage based on complete response to preoperative therapy. This neoadjuvant regimen is effective in patients with squamous carcinoma and adenocarcinoma. These preliminary results demonstrate an improved median and actuarial survival compared with historical controls in 137 patients operated on between 1966 and 1985 at our institution. PMID- 8347011 TI - Aortic coarctation with hypoplastic arch in neonates: a spectrum of anatomic lesions requiring different surgical options. AB - Hypoplasia of the transverse aortic arch is frequently associated with isthmic coarctation in many patients referred for operation in early infancy, and the surgical technique should be adjusted to suit each type of anatomic lesion. Referring to the anatomic description of hypoplastic aortic arch reported by Moulaert and associates, between January 1988 and July 1991 we operated on 32 consecutive infants (< or = 3 months old) using a surgical approach based on the echocardiographic and angiographic findings; 20 patients (62%) were younger than 2 weeks of age and 20 patients (62%) had associated intracardiac lesions. According to the location, extension, and size of the hypoplasia of the aortic arch, we had three groups of patients: in group 1 (21 patients) we performed resection and extended end-to-end anastomosis, as previously described in 1985; in group 2 (5 patients) we performed resection, posterior end-to-end anastomosis, and anterior subclavian flap enlargement; and in group 3 (6 patients) we performed direct side-to-end anastomosis between ascending and descending aorta through a median sternotomy. One patient died during the postoperative course in group 3. With a mean follow-up time of 26 months we had 4 cases (13%) of "residual" or "recurrent" coarctation in group 1, successfully repaired at 2 months of age by an anterior approach in 2 patients and by percutaneous angioplasty in the others. In conclusion, hypoplastic aortic arch in neonates represents a common difficulty, and optimal reconstruction of the entire aortic arch is mandatory to reduce operative mortality and incidence of recoarctation, especially when there are complex associated intracardiac lesions or left ventricular dysfunction. PMID- 8347012 TI - Valve morphology in complete atrioventricular septal defect: variability relevant to operation. AB - The remodeling of the atrioventricular valves in patients with complete atrioventricular septal defects is the crucial part of surgical repair. Variability in valve morphology is an important factor. This study evaluates the variability in morphology of the anterior and posterior leaflets in 30 heart specimens. All hearts had an anterior bridging leaflet: Rastelli type A in 12, type B in 2, and type C in 16. The posterior leaflet revealed four morphologic patterns: a right- and left-sided posterior leaflet, both inserting directly onto the crest of the ventricular septum (5 hearts); a common posterior leaflet attached to the septal crest by a membrane (2 hearts); a common posterior leaflet attached to the septal crest by multiple chordae (13 hearts); and a virtually free-floating posterior leaflet (11 hearts). The categorization is surgically relevant in making a distinction between hearts with and without an interventricular communication underneath the posterior leaflet. Surgically relevant variations occurred also in arrangement and positioning of chordae originating from the right septal side. There was no relationship between the Rastelli classification of the anterior leaflet and that of the posterior leaflet. The variability in morphology of the posterior leaflet and its attachments to the ventricular septum appear equally crucial for successful repair as that of the anterior leaflet. PMID- 8347013 TI - Warm blood cardioplegia: ultrastructural and hemodynamic study. AB - Forty patients with coronary artery disease were included in this study. Half of them received cold crystalloid and cold blood cardioplegia (group 1), and half received normothermic blood cardioplegia (group 2). In group 1, left ventricular stroke work index was 24 +/- 3 g.m/m2 1 hour after the operation, 29 +/- 8 g.m/m2 12 hours after the operation, and 33 +/- 6 g.m/m2 24 hours after the operation. In group 2, left ventricular stroke work index was 37 +/- 4 g.m/m2 1 hour after the operation, 37 +/- 4 g.m/m2 12 hours after the operation, and 44 +/- 7 g.m/m2 24 hours after the operation. Myocardial oxygen extraction 20 minutes after the termination of cardiopulmonary bypass was 0.28 +/- 0.03 in group 1 and 0.44 +/- 0.08 in group 2. Myocardial lactate extraction at the same time was -0.09 +/- 0.02 in patients receiving cold blood cardioplegia and 0.17 +/- 0.07 in patients receiving normothermic blood cardioplegia. Electron microscopic study revealed no calcium accumulation in the mitochondria in group 2 patients, whereas calcium accumulation was present in the other group. PMID- 8347014 TI - Subxiphoid approach for insertion of ICDs after previous median sternotomy. AB - To avoid the risks both of repeat median sternotomy and of thoracotomy, the modified subxiphoid approach was adopted for insertion of implantable cardioverter-defibrillators in 10 patients who had previously undergone cardiac operations via median sternotomy. Effective implantable cardioverter defibrillator systems were implanted in all patients. There were no operative deaths and no hemorrhagic or respiratory complications. One patient underwent repositioning of a dislodged superior vena caval electrode, and an infected generator pocket developed in 1 patient. Early extubation was routine. Two patients were observed in the coronary care unit for the first postoperative night. Postoperative pain was controlled with oral analgesic agents. The subxiphoid approach is safe and effective, and it carries a substantially lower risk of complications than other techniques, even in this high-risk group of patients. By minimizing the need for admission to the intensive care unit, invasive monitoring, and prolonged ventilatory support, by reducing surgical complications, and by shortening the hospital stay, the subxiphoid approach saved an average of $3,295 per patient. PMID- 8347015 TI - Functional results of left ventricular reconstruction. AB - From 1988 to 1991, 48 patients with left ventricular aneurysm underwent endoventriculoplasty with a circular patch to preserve the left ventricular geometry. Of these patients, 98% underwent concomitant myocardial revascularization, and in 77% the left anterior descending coronary artery was bypassed. The overall operative mortality rate was 4.1%. The 3-year survival rate was 91%, and 67% of patients had no further cardiac complications. Cardiac performance was assessed postoperatively by ventriculography in 28 patients. The global ejection fraction rose from 0.39 +/- 0.11 to 0.57 +/- 0.14 (p < 0.001); the left ventricular end-diastolic pressure fell from 20 +/- 7.5 mm Hg to 15 +/- 7.8 mm Hg (p < 0.05). Computerized analysis of regional contraction revealed a significant improvement in the anterolateral and apical segments and in the transitional zone. In 61% of the patients, a normal contraction pattern resumed, whereas in the remaining 39%, a residual deformity of the left ventricular chamber was present. The best results were obtained in patients with a preserved proximal septum at echocardiography. PMID- 8347016 TI - Expandable prosthesis in right postpneumonectomy syndrome in childhood and adolescence. AB - Right pneumonectomy can lead to severe respiratory impairment due to stenosis of the left main bronchus. This syndrome is usually treated by inserting a fixed volume prosthesis but, in children, expandable prostheses have the advantage of being adaptable to growth and permit progressive recentering of the mediastinum. We report 3 such cases, with the results of pulmonary function tests. The patients were aged 11, 17, and 22 years at the time of implantation and had undergone pneumonectomy during childhood for either bronchiectasis or complete pulmonary sequestration. All 3 patients are doing well, with a follow-up of 1 to 3 1/2 years. Pulmonary function tests have shown a substantial improvement in the obstructive syndrome in 2 patients whereas, in the third patient, in whom the contralateral lung was not perfectly healthy, the functional improvement was only moderate. PMID- 8347017 TI - Phrenic nerve damage via a right thoracotomy in older children with secundum ASD. AB - Phrenic nerve damage (PND) in children after cardiac operations is now recognized as being more frequent than previously thought. In a prospective study on 400 children, we previously demonstrated electrophysiologic evidence of postoperative PND in approximately 16% of patients, with one third of cases occurring in children under 18 months. In the past 18 months, 30 children have had atrial septal defect (ASD) repairs as their only operative procedure. Fourteen children had ASD repairs via a midline incision, and 16 ASD repairs were via a right thoracotomy. No PND (assessed by phrenic nerve latency) was found after a midline approach. In the right thoracotomy group, 5 children had evidence of PND (31%; p = 0.05). Four of these 5 patients were female and more than 14 years of age. The incidence of damage in this pubescent group was 80% (p < 0.05). In the older age group the duration of ventilation was not prolonged, but affected patients had symptoms of fatigue and breathlessness postoperatively. These data suggest a strong association between right thoracotomies for ASD repairs and PND, especially in the female pubescent group when a low submammary skin incision (seventh to eighth space) is used with a fifth to sixth space entry into the thoracic cavity. In conclusion, the right thoracotomy approach for ASD repair appears to be a significant risk factor for PND in older children. PMID- 8347018 TI - Use of intraoperative mapping to optimize surgical ablation of atrial flutter. AB - The purpose of this study was to develop a surgical treatment for atrial flutter using intraoperative activation sequence mapping to minimize the surgical procedure necessary to ablate the flutter. A canine model (n = 10) of left atrial enlargement was developed by creating a shunt from the left subclavian artery to the left superior pulmonary vein. Sustained atrial flutter was easily induced in this model. The flutter consisted of a single reentrant circuit that rotated around one or two anatomic obstacles linked by a region of functional block. Epicardial templates, consisting of 252 bipolar electrodes, were used to record activation time maps. After localization of the reentrant circuit, surgical incisions were placed to interrupt the pathways. In all 10 animals, flutter could be induced and intraoperative mapping localized the reentrant circuit. Seven circuits were in the right atrium and three were in the left atrium. The operation ablated all of the preoperative circuits. However, in 5 of the animals, flutter originating from a new circuit could be induced. Activation sequence mapping before and after operation demonstrates that there are multiple potential reentrant pathways in this canine model of atrial flutter. Therefore, all potential pathways must be surgically interrupted to prevent inducibility of atrial flutter. PMID- 8347019 TI - Determinants of heart-lung transplantation outcomes: results of a consensus survey. AB - Substantial progress has been made in clinical heart-lung transplantation. Although outcomes vary across centers, 1-year patient survival is now 59%. This study was an attempt to assess consensus among transplant program directors regarding the major determinants of patient outcome. In the National Cooperative Transplantation Study we evaluated consensus through a survey of all heart-lung transplant programs active in 1988. Of the eligible programs, 23 (85%) returned completed surveys. Data on the medical and surgical determinants of outcome were analyzed. There was considerable consensus among program directors as to the importance of several factors. The three most critical predictors of favorable outcomes were periodic pulmonary function tests to detect rejection (85.7%), avoidance of use of prednisone during the first 14 days after transplantation (76.2%), and annual left and right heart catheterization with coronary arteriography (76.2%). Several approaches were considered undesirable or unnecessary. These included electrocardiogram as standard rejection monitoring technique (71.4%), cytoimmunological monitoring as standard rejection monitoring technique (66.7%), and routine steroid discontinuation after transplantation (66.7%). On various other treatment approaches there was little evidence of consensus. These included prophylaxis with acyclovir and severe bronchiolitis as a criterion for retransplantation. Although controversial, consensus conferences are one means by which to evaluate technological innovations. Based on their results, practice guidelines can be developed to better inform third-party payers on issues related to transplantation. PMID- 8347020 TI - Postcardiotomy shock: clinical evaluation of the BVS 5000 Biventricular Support System. AB - This prospective trial evaluated the safety and efficacy of a new pulsatile, temporary ventricular assist device, the BVS 5000. Patients were eligible for treatment if they were hemodynamically unstable despite maximal pharmacologic and intraaortic balloon pump therapy, were free of concomitant complications, and were less than 6 hours from the first attempt to separate from cardiopulmonary bypass. Fifty-five postcardiotomy patients were enrolled; 31 met all selection criteria and the remainder failed to meet criteria (n = 15) or were not successfully supported (n = 9). The BVS 5000 effectively restored hemodynamics: Mean arterial pressure increased (77.1 +/- 8.0 mm Hg on-support versus 50.1 +/- 15.3 mm Hg presupport; p = 0.0001). Cardiac index increased (2.3 +/- 0.3 L.min 1.m-2 on-support versus 1.6 +/- 0.6 L.min-1.m-2 presupport; p = 0.0013). Left ventricular filling pressure decreased (11.9 +/- 4.5 mm Hg on-support versus 23.8 +/- 8.7 mm Hg presupport; p = 0.0030). The most frequent complication was bleeding in 42 patients (76%). Of the patients meeting all criteria, 17 (55%) were weaned from support and 9 (29%) were discharged. Survival was significantly influenced by presupport cardiac arrest events. Survival among patients not experiencing arrest was 47%. Eight patients are long-term survivors and were asymptomatic in New York Heart Association class I or II at 1-year follow-up. The BVS 5000 restored hemodynamics, permitted myocardial recovery, and improved survival in a group of patients who would have otherwise died. PMID- 8347021 TI - Hemorrhage due to inflammatory erosion of the pulmonary artery stump in postpneumonectomy bronchopleural fistula. AB - Bleeding from the pulmonary artery in patients with a bronchopleural fistula after pneumonectomy is a rare but devastating complication. The incidence is unknown, but our data suggest an incidence of 4% in all postpneumonectomy bronchopleural fistulas. Two case histories are presented in which the anterior transpericardial approach was used to stop the pulmonary bleeding by direct suturing. Nevertheless, 1 patient died 5 days later because of irreversible brain damage; the other patient recovered well after a protracted convalescence. PMID- 8347022 TI - Transesophageal Doppler echocardiographic monitoring for malperfusion during aortic dissection repair. PMID- 8347023 TI - Mechanical assist device for right ventricular failure after acute aortic dissection. AB - Acute myocardial ischemia and infarction due to retrograde coronary artery dissection are uncommon complications after ascending aortic dissection. A case of acute aortic dissection with massive right ventricular failure successfully treated by replacement of the ascending aorta and postoperative right ventricular mechanical support is presented. Although mechanical assistance may be hazardous after ascending aortic replacement, because of the need of anticoagulation, it represents a valid therapeutic option when severe right ventricular failure due to acute myocardial infarction ensues. PMID- 8347024 TI - Combination gastric seromuscular patch and omental pedicle flap for bronchial fistula. AB - We report the successful closure of a recurrent bronchial fistula using a combination gastric seromuscular patch and omental pedicle flap. This new method provided an immediate airtight closure of the bronchial fistula. This technique appears superior to closure by omentum alone. PMID- 8347025 TI - Intraaortic balloon entrapment. AB - A review of intraaortic balloon pump use at the University of Miami/Jackson Memorial Medical Center over the past 21 years identified 2 cases where a balloon was found to be entrapped. The balloon catheters had been in place for approximately 10 days when this complication occurred. The retained balloons were torn, filled with clotted blood, and impacted in the vasculature. In our first case, forceful removal of the intraaortic balloon was complicated by unintentional extraction of the external iliac and common femoral arteries. In the second case, clot within the balloon was dissolved with tissue plasminogen activator injected into the drive lumen of the catheter before removal. The prevention and management of this rare but serious complication of intraaortic balloon pumping is reviewed. PMID- 8347026 TI - Bullet embolization to a coronary artery. AB - A rare case of coronary artery embolization is presented. A 48-year-old man arrived with multiple pellet wounds, severe chest pain, and an inferior myocardial infarction. Chest roentgenograms showed one of the pellets overlying the cardiac shadow, and coronary arteriography revealed complete occlusion of the posterior descending branch of the right coronary artery with a radiopaque foreign body, which corresponded exactly to the pellet first seen. Intravascular arterial embolization of small caliber bullets has been reported in the abdomen, lower extremities, and the carotid territory. Here we report such an event occurring in the coronary circulation. PMID- 8347027 TI - Management of giant coronary artery aneurysm with fistulization into the right atrium. AB - A giant right coronary artery aneurysm communicating with the right atrium is reported. Its diagnosis using echocardiography, computed tomography of the chest, and angiography is illustrated. The operative management of this rare cardiac pathology is described. The role of operation in such a large aneurysm is emphasized. PMID- 8347028 TI - Metastatic malignant schwannoma in the heart. AB - A rare case of metastatic malignant schwannoma is described. The secondary tumor in the right lung grew along the pulmonary vein and filled almost the whole of left atrium. Operation was later performed, and a large tumor extension from the left atrium was removed. PMID- 8347029 TI - Esophageal schwannoma. AB - A 56-year-old woman was seen with an abnormal shadow on chest radiogram. Evaluation revealed an esophageal tumor, which was resected. The tumor was found in the muscular layers of the esophagus; esophageal schwannoma was diagnosed by light microscopic and immunohistochemical studies. There was no relationship between the tumor and vagus nerve. The tumor demonstrated partially invasive growth, and mitotic figures were occasionally observed. PMID- 8347031 TI - Successful left ventricular assist after a first and second heart operation. AB - Progressive coronary artery disease and recurrent symptoms developed in a 57-year old man. Nine years earlier he had undergone coronary artery bypass grafting and was supported with a centrifugal left ventricular assist device. He underwent redo coronary artery bypass and again required left ventricular assistance. The patient recovered and was discharged on the 15th postoperative day. He is doing well 1 year after operation and has good left ventricular function. PMID- 8347030 TI - Management of an innominate artery aneurysm during an open heart operation. AB - A 76-year-old woman was found to have a 4 x 2.5-cm saccular aneurysm at the origin of the innominate artery at the time of a reoperative open heart operation. The operative procedure was modified to include repair of the aneurysm with a Dacron patch. During the period of innominate artery occlusion, the patient was cooled to 25 degrees C and the mean arterial pressure was maintained at 90 mm Hg to maximize cerebral protection. PMID- 8347032 TI - Use of cardioplegia delivery equipment for rapid warm volume replacement after cardiopulmonary bypass. AB - Often, after cardiopulmonary bypass involving aortic dissection, aortic root replacements, or valve conduits, rapid volume replacement with blood products is essential to obtain hemostasis and patient survival. We describe a method of using cardiopulmonary bypass equipment for rapid warm volume replacement and infusion of remaining residual volume in the cardiopulmonary bypass circuit after a cardiac operation. PMID- 8347034 TI - Saphenous vein preparation for coronary artery bypass grafting using a cardioplegia delivery set. AB - Many techniques of saphenous vein preparation for coronary artery bypass grafting and their relation to endothelial preservation and graft patency have been published. We describe a method for final preparation of saphenous vein segments that uses the patient's undiluted heparinized blood infused at physiologic arterial pressure with a standard cardioplegia delivery apparatus. This method provides excellent demonstration of vein caliber and allows for quick identification and control of any previously undetected side branches or leaks. No additional equipment or instruments are required, and preparation can be performed before or after the institution of cardiopulmonary bypass. PMID- 8347033 TI - Technical modification for anastomosis of low-lying coronary ostia in Bentall procedure. AB - Bentall procedure is not advisable when the origins of the coronary artery ostia cannot reach the composite valve graft at a satisfactory level for direct reimplantation. The other alternatives to coronary artery ostia reimplantation have some disadvantages. A technical modification of the Bentall procedure, successfully used in 3 patients and allowing direct coronary reimplantation without any tension on the suture line, is described. PMID- 8347035 TI - Intraoperative procurement of autologous fibrin glue. AB - A method of intraoperative procurement of autologous fibrin glue is described. The relative efficacy of our autologous preparation is compared with that of fibrin glue made with homologous cryoprecipitate. Experimentally, the fibrinogen content and the strength are less than those found in cryoprecipitate and appear related to the fibrinogen content of the autologous plasma used as substrate in the fibrin glue reaction. Clinically, no significant differences are noted in the performance of autologous fibrin glue. We believe the absence of the risk of blood-borne infection with the autologous product is a major advantage. PMID- 8347036 TI - Cardiac hemangiomas. AB - Cardiac hemangiomas are rare benign vascular tumors of the heart. To date, 23 cases have been reported. Symptoms are usually due to compression of cardiac structures or obstruction of outflow tracts. Echocardiography usually directs the diagnosis toward a cardiac mass. Enhanced-contrast computed tomographic scan or magnetic resonance imaging establishes the diagnosis of hypervascularized cardiac tumor. Coronary arteriography establishes the diagnosis by showing the characteristic tumor blush. Surgical resection is done using cardiopulmonary bypass. Long-term outcome is favorable. PMID- 8347037 TI - Preoperative glucose-insulin-K+ therapy for cardiac protection: what can be recommended? PMID- 8347038 TI - How to prevent pleural opening in harvesting the internal mammary arteries. PMID- 8347039 TI - Hypothermic thoracoabdominal aneurysm operation. PMID- 8347040 TI - Sense, antisense, nonsense, and missense. PMID- 8347041 TI - Release of vasoactive substances during cardiopulmonary bypass. PMID- 8347042 TI - Device-supported myocardial revascularization. PMID- 8347043 TI - Bronchial polyp secondary to foreign body. PMID- 8347044 TI - Septal myocardial infarction: a complication of coronary artery stay sutures. PMID- 8347045 TI - Adverse hemodynamic effects of pericardial closure soon after an open heart operation. PMID- 8347046 TI - Simple way to improve right ventricular flow distribution during continuous retrograde cardioplegia. PMID- 8347047 TI - [The 50th anniversary of the Secretaria de Salubridad y Asistencia Pblica, today the Secretaria de Salud (1943-1993). The year 1943 and the transformation of Mexican medicine]. PMID- 8347048 TI - [Coronary angioplasty in 40 patients with 518 stenoses: complications and surgical support]. AB - We analyze the outcome of 400 patients (pts) with coronary angioplasty in 518 stenosis (314 men, age 29 to 80). The clinical syndromes were unstable angina in 252 pts, acute myocardial infarction (MI) in 26, angina or residual ischemia after thrombolysis for MI in 34 and 18 pts with post-MI angina. Success was achieved in 478 of 518 segments (92%). Mean stenosis was reduced from 88 to 15%. Revascularization was complete in 92% of pts. Primary success was 74% in total occlusions. We had 25 major complications (6%): 8 emergency bypass surgery (2%), MI in 12 pts (3%) and 5 deaths (1%). The procedures were performed without surgical standby in 220 pts: in 68 it was an emergency and in 152 it was considered a low risk procedure. Major complications in emergency cases were 3 MI (4%) and 2 deaths (3%). In the low risk procedures there were no deaths, 3 MI (2%) and 1 aortic dissection. We conclude that in well selected patients coronary angioplasty gives a high success rate with very few complications. Furthermore, it is possible to identify a very low risk subset of patients in whom the procedure can be performed without having a surgical standby. PMID- 8347049 TI - [The treatment of severe mitral stenosis by percutaneous transvenous commissurotomy]. AB - In 110 adult selected patients, 87.1% female (average age 38.2 years, range 16 72) with symptomatic, severe mitral stenosis eligible for surgery, we performed balloon catheter transvenous mitral commissurotomy (BCTMC) as alternative treatment. Inoue's catheter was utilized in 80 cases (72.7%), and the double balloon technique in 30 (27.3%). The procedure was successful in 102 patients (92.7%, 2nd attempt in 5 cases), with optimal results in 96 (87.3%); and it was unsuccessful in one patient for a technical difficulty. Complications occurred in 3 cases due to perforation of a cardiac chamber (2.7%); and 4/106 patients developed severe mitral insufficiency (3.8%). The mitral valve area increased from 1.09 +/- 0.27 to 2.6 +/- 0.87 cm2 (p < 0.0001); the diastolic mitral gradient decreased from 18.9 +/- 5.9 to 3.6 +/- 2.8 mmHg (p < 0.0001); similar reduction was obtained in mean left atrial pressure from 26.2 +/- 6.5 to 12.5 +/- 4.2 mmHg (p < 0.0001), and mean pulmonary artery pressure from 38 +/- 17 to 26.2 +/- 10.4 mmHg (p < 0.005). New mitral insufficiency appeared or increased in more of one grade in 12/106 patients (11.3%), and it was not detectable in 86/106 patients. During long-term follow-up (average 10.4 months, range 5 to 24), all patients (100 cases) improved their functional class (83.1% asymptomatic), and maintained their 2D echocardiographic mitral valve area. In conclusion BCMTC is the treatment of choice for selected cases of acquired symptomatic mitral stenosis, with immediate and long term results comparable to surgical commissurotomy. PMID- 8347050 TI - [The absence of characteristics lesions in the microcirculation of non-insulin dependent diabetic patients]. AB - Diabetic cardiomyopathy apparently has an important role in the increased cardiovascular morbi-mortality of diabetic patients and its cause is likely to be secondary to small vessel disease. We undertook the present study to compare small and large vessel disease in hearts of patients who died with coronary disease, and determine how diabetes and/or hypertension correlates with these findings. The paraffin blocks of 52 hearts were used in this study. Cases were selected if they died from coronary artery disease and excluded if they had a previous angioplasty, revascularization surgery, congenital, rheumatic or other causes of heart disease. They were divided in two groups; diabetics and non diabetics and each group was subdivided in hypertensives an non hypertensives. They were matched by age and sex. DM duration was 11 +/- 6 years and known hypertension of 10 +/- 4 years with no significant differences between both groups. The results were recorded without knowledge of patients clinical findings. Atherosclerotic heart disease was more advanced in DM patients, with an increased prevalence of three vessels disease, and more extensive myocardial infarctions. Diabetic subjects had increased (non significant) basal membrane thickening of the capillaries. We could not find differences in parenchymal hypertrophy, interstitial edema, proliferative endothelial lesions and luminal width in middle and large size vessels. Hypertensive patients had increased perivascular fibrosis (NS). Our results suggest that advanced atherosclerotic heart disease is more common in diabetic patients and diabetic cardiomyopathy, if present, seems not to related to a particular structural microvascular disease. PMID- 8347051 TI - [Sudden death and the congenital long QT syndrome (Romano, Ward and Barlow)]. AB - We present four cases, a mother and three sons with Romano, Ward and Barlow syndrome (long QT without deaf-muteness) controlled over the past 20 years. The mother died suddenly at the age of 42, as did two sons at 24 and 17 years. A retrospective study was conducted comprising the three generations prior to the mother, and a high rate of sudden death was found. Possible causes were analyzed with a view to implementing proper prophylaxis treatment for ventricular tachycardia or fibrillation as causes for syncopal patterns and sudden death. Therefore, digital, left stellectomy and betablocker effects were analyzed. The anatomical study of the patient who died at 17 years is presented, and finally the new perspectives of the syndrome in terms of possible recognition of the responsible gene, as well as the convenience of implanting new defibrillating cardioverters, were evaluated. PMID- 8347052 TI - [High doses and the rapid infusion of streptokinase for the treatment of massive pulmonary thromboembolism]. AB - We report the case of a 65 year old woman with no prior cardiac or pulmonary disease, who suffered pulmonary embolism (PE); diagnosis was made on the basis of the existence of risk factors, clinical, radiographic and electrocardiographic features, and a lung scan with perfusion defects and normal ventilation. PE was considered massive because the patient developed acute respiratory failure that required tracheal intubation and mechanical ventilation as well as obstructive shock, electrocardiographic and echocardiographic data of right ventricle overload, and pulmonary hypertension, with pulmonary artery pressure of 38 mmHg. She received an initial treatment with high doses (1,500,000 UI) and rapid infusion (1 hr) of intravenous streptokinase (SK) followed by heparin anticoagulation. Thereafter the hemodynamic disturbances improved and pulmonary artery pressure post-thrombolysis was 23 mmHg. In this report SK at high doses and rapid infusion showed effectiveness and security. We emphasize the usefulness of echocardiography as a diagnostic aid in patients with a previously healthy cardiopulmonary system, as well as the possible role of electrocardiogram as an early indicator of pulmonary reperfusion. This could be the first report of successful thrombolysis with high doses and rapid infusion of SK in massive PE. PMID- 8347053 TI - [Variations in hemostasis and fibrinolysis during the treatment of acute myocardial infarct (AMI) with tissue-type plasminogen activator (TTPA). A study of 17 cases]. AB - The aim of this trial was to estimate changes in the coagulation and fibrinolysis systems during the thrombolytic treatment with recombinant human tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction and correlate with hemorrhagic complications. We studied 17 patients with a 3 hours continuous systemic infusion of 100 mg of rt-PA. Prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen splits products, plasminogen, alfa-2-antiplasmin (a-2AP) and antithrombin III (AT-III) were performed before, during and after infusion. Most patients showed lengthening coagulation times. Fibrinogen and plasminogen were decreased and PDF was increased. No variations in alpha-2AP or AT-III were observed. The recuperation of fibrinogen levels occurred in 3 hours and there was hyperfibrinogenemia after day 3. No hemorrhagic complication was observed in patients with abnormalities in these coagulation or fibrinolytic tests. PMID- 8347054 TI - [The anti-arrhythmia effect of carbamazepine in chagasic patients with advanced myocardial damage]. AB - Oral administration of 600 mg/day of carbamazepine to 14 arrhythmic chagasic patients with advanced myocardial damage and no signs of congestive heart failure did not alter the frequency of ventricular extrasystoles, but reduced the total number of supraventricular ectopic beats in 7/14 patients and the episodes of complex ventricular arrhythmias in up to 43% of patients. This assessment was made from 24 hour continuous Holter recording during the course of this double blind, placebo controlled, randomized crossover study. Serum levels of carbamazepine were also determined and found within therapeutic limits. Six patients complained of minor side effects. One patient presented with iatrogenic complete AV block, another case had proarrhythmic effect and one patient had to be withdrawn from the study because of gastric irritation. No instance of contractile depression was observed. Accordingly, carbamazepine is a therapeutic alternative for treatment of symptomatic complex ventricular or supraventricular arrhythmias in chronic chagasic patients without evidence of conduction system involvement or with intolerance to other antiarrhythmic drugs. PMID- 8347055 TI - [Cerebral ischemia: a complication in heart catheterization. An assessment in 2178 catheterizations]. AB - Cardiac catheterization is highly recognized as the more definitive test in several cardiac diseases. However it has a small but definite risk. Cerebral ischemia is an unusual complication of this procedure; the main recognized physiopathological mechanism is thromboembolism. We present the analysis of 7 cases observed in 2178 consecutive cardiac catheterizations. In all cases the neurological dysfunction developed during the procedure or in the few minutes after it. One patient had a complete cerebral infarct. All cases of cerebral infarct were confirmed with computed tomography scan or magnetic resonance imaging. The clinical profile supported an embolic mechanism. The early recognition and management of this complication can influence the prognosis of these patients and therefore emphasize the importance of the monitoring of the neurological function in the hemodynamic department. PMID- 8347057 TI - [The direction of Mexican electrovectorcardiography]. PMID- 8347056 TI - [Transesophageal electrophysiological study. A report of 2 cases]. AB - Intraesophageal electrocardiography and transesophageal atrial pacing are procedures used for the study of supraventricular arrhythmias. A systematic study and integration of these two techniques on the part of the author lead him to develop a methodology for noninvasive electrophysiological supraventricular studies. The methodology is based on low-energy transesophageal atrial pacing and on a simultaneous recording system with unipolar and bipolar intraesophageal leads, bipolar transthoracic leads and body surface leads. The frequency range, amplitude and velocity of the recording play an important role. A pharmacological protocol is studied for each patient. Aspects of the methodological contribution are briefly documented for two cases. This method is a good alternative for supraventricular electrophysiologic study but is limited when compared to invasive procedures. PMID- 8347058 TI - [The participation of the endothelium in physiopathological processes]. PMID- 8347059 TI - [Cyclic ureas. 2. Racemates and enantiomers of imidazolidin-2-ones: synthesis, configuration and sedative-hypnotic action]. AB - The racemates and the enantiomers of the imidazolidin-2-ones 2a and 2b, which can be considered as cyclic ureas, are obtained from the racemates and the enantiomers of the hydantoins 1a and 1b by reduction with LiAlH4/AlCl3. The enantiomers that are dextrorotating in ethanol possess S-configuration. In a study with Wistar-rats, 2a and 2b show sedative-hypnotic activity. The enantiomers exhibit marked enantioselective differences in their potency. PMID- 8347060 TI - [Synthesis and biological effects of new N,N-disubstituted 5-alkyliden- and 5 aralkyliden-3-aminorhodanines]. AB - Numerous novel N,N-disubstituted 5-alkyliden- or 5-aralkyliden-3-aminorhodanines 2 have been prepared by condensation of carbonyl compounds with 1. The effectiveness of some derivatives in an "akanthose test" with hairless mice was shown. PMID- 8347061 TI - High-performance liquid chromatographic analysis of cyclosporine A in human skin. AB - A three-dimensional high-performance liquid chromatography (HPLC) method is described for the determination of cyclosporine A in human skin. The method allows to determine at least 3 ng cyclosporine A in 10 mg skin (total sample amount needed) and is suitable for cyclosporine A level monitoring in the skin of psoriatic patients. PMID- 8347062 TI - Applying quantitative methods to the prediction of full functional recovery in adult rehabilitation patients. AB - The purpose of this project was to construct a pilot prognostic index for use in research and clinical practice that would predict functional recovery in adult rehabilitation patients at discharge using clinical characteristics at admission to rehabilitation (independent performance of seven activities of daily living and three basic mobility tasks). We constructed the index from retrospectively collected data on 1,020 adult rehabilitation patients who underwent rehabilitation between 1980 and 1986. Adjusting for patient characteristics, the odds of recovering independent function doubled for each ten-point increase in the 100-point functional status score measured at admission to rehabilitation (odds ratio = 2.1, 95% confidence interval [CI] = 1.9 to 2.4). The odds increased by a factor of 1.9 (95% CI = 1.1 to 3.2) in patients with an impairment considered more functionally reversible and by a factor of 2.1 (95% CI = 1.3 to 3.4) in patients transferred from an acute hospital. The odds of functional recovery decreased in those over 79 years of age, in those who were unemployed before hospitalization, and as the number of comorbid conditions increased. Our findings demonstrate the feasibility of developing quantitative estimates of functional prognosis. Prior to use, the index should be externally validated in different rehabilitation facilities. PMID- 8347063 TI - Does functional reach improve with rehabilitation? AB - Functional reach (FR, maximal safe standing forward reach) is a precise, reliable, clinically accessible, age-sensitive measure of balance that approximates center of pressure excursion and validly estimates physical frailty. We now test its ability to detect improvement in balance over time. Twenty-eight inpatient male veterans (age 40 to 105, mean, 67.3) undergoing physical rehabilitation and 13 nonrehabilitation controls were evaluated at baseline and every 4 weeks using FR (yardstick method), 10-foot walking time (WT), the Duke hierarchical mobility skills protocol (HMS) and a portion of the Functional Independence Measure (FIM). Their sensitivity to change was determined using the responsiveness index (RI). FR as well as the other physical performance instruments tested were found to be sensitive to change (RI for FR = 0.97, WT = 11.26, HMS = 4.63, FIM = 4.93) and therefore, appropriate measures for use in prospective clinical trials. PMID- 8347064 TI - Assessment of hand function in Duchenne muscular dystrophy. AB - Eighteen boys with Duchenne muscular dystrophy (DMD) were assessed for their ability to perform tasks involving wrist and hand function. Each subject was assessed using the Jebsen Test of Hand Function, range of motion measurements, and muscle strength tests. Writing and simulated page turning were performed successfully by boys in all age groups. Boys over age 15 had difficulty completing simulated feeding and picking up large and small objects. The muscle strength of the wrist extensors and the radial deviation range of motion at the wrist were found to be strongly correlated with six of the seven tasks assessed. These two clinical assessments appear to be good indicators of overall wrist and hand function. Life expectancy with DMD is increasing with advances in respiratory care making preservation of wrist and hand function, the major activity remaining with advanced disease, increasingly important. PMID- 8347065 TI - Elbow joint restriction: effect on functional upper limb motion during performance of three feeding activities. AB - This study was conducted to quantify and compare changes in upper limb joint motion during different feeding tasks when the elbow joint was restricted. Ten male and nine female volunteer subjects age 18 to 50 years participated; all were healthy, right dominant, with no upper limb pathology. A splint was used to restrict elbow joint motion. Three feeding tasks under both unrestricted and restricted conditions were randomly assigned; motion was recorded by a video based three-dimensional motion analysis system. Elbow restriction resulted in significantly (p < .05) larger arcs of motion in shoulder flexion and internal rotation. Differences between feeding types were similar during both unrestricted and restricted conditions. Increased shoulder joint motion resulting from elbow joint restriction may require greater activity of shoulder girdle muscles increasing the risk of soft tissue problems and degenerative joint disease. Decisions regarding elbow immobilization should take into consideration potential effects upon total upper limb motion. PMID- 8347066 TI - Behavior analysis and intervention during hospitalization for brain trauma rehabilitation. AB - Continued problematic behavior in children and adolescents after brain trauma is a major barrier to medical care, rehabilitation, and eventual independent living. The present study demonstrates the application of already well-developed behavior analysis techniques to the early posttrauma expression of behavior problems during hospital recovery. To satisfy concerns regarding both cost and individualized treatment, interventions were carried out primarily by regular hospital staff (nurses and therapists), medical record data were used to document gains, and time series, within subject designs were used to show experimental control. Four patients (three male and one female) ranging in age from 10 to 16 years, received intervention based on behavior analysis techniques, which reduced disruption and increased cooperation with therapy and medical care. Behavior analysis techniques will be relevant to future rehabilitation research to the extent that the posttrauma patient's behavior is effected by environmental consequences as demonstrated here. PMID- 8347067 TI - Attitudes of medical students and health-care professionals toward people with disabilities. AB - This study used the Attitude Towards Disabled Persons Scale (ATDP) to investigate differences in attitudes toward individuals with physical disabilities among first-year and fourth-year medical students and health-care professionals. Of 851 questionnaires sent out, 310 were returned, and 297 were used in the final analyses. The fourth-year medical students had significantly more positive attitudes toward people with physical disabilities when compared to the first year medical students. Differences between health-care professionals and fourth year medical students were nonsignificant. Across the sample, females, compared to males, and whites, compared to Asians, were found to hold significantly more positive attitudes toward people with physical disabilities. Contact with people with physical disabilities did not have to be on an equal-status basis to have a positive effect on attitudes toward people with physical disabilities. The need for health and educational disciplines to further the movement towards integration of people with physical disabilities was emphasized, and suggestions for future research were offered. PMID- 8347068 TI - Balance, reaction time, and muscle strength in exercising and nonexercising older women: a pilot study. AB - Twenty-one women, aged 57 to 75 years, who had been taking part in exercise programs for periods of 12 months or more underwent tests of muscle strength, reaction time, proprioception, and body sway. The performance of these women in the tests was compared with 21 women of the same age who were not taking part in any organized physical activity and were not exercising more than 30 minutes a day. The women who had been taking part in the exercise program performed significantly better in the tests of quadriceps strength, reaction time, and sway on a compliant surface than the nonexercising women. The exercisers also had lower body mass index scores. These pilot results suggest that exercise may play a role in improving a number of sensori-motor systems that contribute to stability, and that exercise of this nature may help prevent falls in older women. PMID- 8347069 TI - Quantitative effects of physical therapy on muscular and functional performance in subjects with osteoarthritis of the knees. AB - Osteoarthritis (OA) of the knees is a functionally limiting disability. Physical therapy (PT) is considered a useful treatment for OA, although evidence is qualitative. The purpose of this study was to quantitatively measure the effects of a 3-month PT program (n = 40; 20 men and 20 women) with knee OA. Muscle function and functional assessment parameters were measured. All data were analyzed by repeated measures analysis of variance (p < 0.05). There were no significant changes in handgrip strength and endurance, limb volume, or angular velocity after PT. Maximal muscle length was significantly increased. Muscle strength significantly increased for the hamstrings (9% and 19%) and quadriceps (8% and 24%) for the men and women, respectively. Endurance improved for the quadriceps (26% and 39%) and hamstrings (18% and 28%) for men and women, respectively. Functionally, there were significant improvements in the ability to climb stairs, rise from a chair, and walk. Walking time (50 ft) and the difficulty and pain of performing various activities decreased. Most improvements had occurred after 1 month of PT. For the first time, the effects of a PT program have been quantitatively measured for patients with knee OA. PMID- 8347070 TI - Reliability of isokinetic and isometric measurement of leg strength on men with mental retardation. AB - The purpose of this study was to determine the reliability of isokinetic and isometric measurement of strength for tests of knee extension and hip abduction on men with mental retardation (MR). In addition, the relationships between isokinetic measures of peak torque (PT) and total work (TW) and isometric peak torque were examined. Twenty-two men with mild to moderate MR were tested for isokinetic knee extension and hip abduction strength on a Musculoskeletal, Evaluation, Rehabilitation and Conditioning (MAREC) systems dynamometer at velocities of 60 and 30 degrees/sec, respectively. Isometric peak torque was determined by an examiner using a Nicholas Manual Muscle Tester (NMMT). Intrarater correlation coefficients for the isokinetic PT and TW scores ranged from .97 to .99, whereas coefficients for isometric NMMT scores ranged from .97 to .98. Pearson correlation coefficients between PT and TW scores ranged from .76 to .93. Coefficients between isokinetic and isometric scores ranged from .43 to .73. These results indicate that highly reliable isokinetic and isometric measurements can be obtained on men with MR. Also, the relatively simple measurement of PT may be the isokinetic parameter of choice at the clinical setting. Moderate relationships between NMMT and isokinetic scores were found, indicating that the generalization of test scores from one test modality to another is not warranted. PMID- 8347071 TI - Comprehensive analysis of dynamic elastic response feet: Seattle Ankle/Lite Foot versus SACH foot. AB - This study evaluated biomechanical and metabolic performance differences between two prosthetic foot designs in light of their mechanical properties. Ten unilateral below-knee amputee subjects, at least 1 year after amputation, capable of walking and running, were studied. Differences in heel and forefoot compliance explained differences in gait events and alignment. Increased efficiency of pushoff in the Seattle Ankle/Lite Foot exists as evidenced by the decrease loading on the opposite limb during double support and a less shortened step length on the sound side compared to the SACH foot. The natural frequency of oscillation for the prosthetic feet was determined to be too high to provide energy storage and release synchronized with kinematic requirements because neither metabolic cost savings nor differences in metabolic efficiency were found. Comfortable walking speed and the nadir of metabolic rate and efficiency are not different. Via accelerometer measurement, it was found that the more compliant and lossy SACH foot heel was less likely to transmit high frequency vibration. PMID- 8347072 TI - Prosthetic profile of people with lower extremity amputation: conception and design of a follow-up questionnaire. AB - A questionnaire, the Prosthetic Profile of the Amputee (PPA), is described both in terms of its conceptualization and design. The objectives of the questionnaire (mail and telephone versions) were to evaluate and to determine the factors potentially related to prosthetic use by a person with a lower extremity amputation after discharge from rehabilitation. The PRECEDE theoretical model (Predisposing Reinforcing and Enabling Causes in Educational Diagnosis and Evaluation) was adapted to the present study and served as a guide for the conceptual basis of the instrument. A multidisciplinary group of 13 experts and another group of eight persons with lower limb amputation were involved in the identification, classification, and priority rating of the factors related to prosthetic use. The design of the questionnaire was structured according to Dillman's Total Design Method. To ensure the content validity of the instrument, the pertinence of each question with regard to the questionnaire's objectives was assessed by the group of experts. Pretesting of the questionnaire was then conducted with a random sample of 26 people with lower extremity amputations. The preliminary version of the instrument has already demonstrated the potential for clinical and research use. PMID- 8347073 TI - Autotraction versus passive traction: an open controlled study in lumbar disc herniation. AB - Autotraction (AT) is a treatment for low-back pain syndrome of benign etiology that uses a specially designed traction table divided into two movable sections. While lying on the table, the pelvis secured, the patient controls the traction forces by grasping and pulling the bars at the head of the table. There are controls for the therapist to apply, through movable sections of the table, rotation and bending forces to help restore mobility to the lumbar spine without inducing pain. The present study is based upon a randomized treatment trial comparing conventional passive traction (PT) to AT. The following outcome indicators were used: (1) subjective response concerning overall improvement, (2) pain intensity (visual analog scale, 0-100), (3) qualitative pain severity (McGill Pain Questionnaire, short-form, 0-45), and (4) pain related disability (Oswestry Low Back Pain Disability Score, 0-100). The favorable response to AT was 75% (30 of the 40 patients) versus the 22% (6 of 27 patients) to PT (p < 0.001). After 3 months, 19 of the 30 responders to AT (63%) reported continued improvement. In these patients, pain ratings remained stable and the disability scores decreased to 0 to 23% of the pretreatment value (median and mean respectively, p < 0.001). PMID- 8347074 TI - Seating and wheeled mobility in the disabled elderly population. AB - Elderly persons constitute the largest among the populations regularly using wheelchairs. This is a review of the few studies specifically concerned with seating for the elderly; it identifies current problems, particularly in the seating for aged people who are in long-term care facilities. This review describes ways of matching currently available seating technology with the needs of disabled elderly persons. Two major barriers to greater use of newer seating technology are (1) the high cost of durable medical equipment and (2) the failure of most clinicians and institutional administrators to recognize the importance of posture and comfort to provide functional independence in wheelchair users. This review discusses seating for four groups of elderly persons: (1) the nonmobile, dependents who may be safety risks and are without energy or ability to wheel or walk by themselves; (2) mobile nonambulatory; and (3) ambulatory, but with special wheelchair needs. Research is needed in wheeled mobility in a number of areas: better matching of mobility to function, cheaper and more effective cushions, more modular seating systems, and better lifting and transfer devices. The American National Standards Institute in cooperation with Rehabilitation Engineering Society of North America has recently recommended standards for wheelchair performance that may be legislated in the next few years. PMID- 8347075 TI - Orthostatic tremor: delayed onset following head trauma. AB - Orthostatic tremor is a 14 to 16Hz (range 7 to 36Hz) tremor of uncertain etiology elicited within seconds of an isometric contraction. It is described as a shaking, cramping of the lower extremities upon standing and is relieved with movement or sitting. Typically patients are unable to stand in place for long periods of time secondary to instability and fatigue. A 73-year-old woman with orthostatic tremor following a history of head trauma is presented. Recognition of the characteristic history and electromyographic findings may lead to appropriate treatment for this annoying and sometimes incapacitating disorder. PMID- 8347076 TI - Analysis of influenza A virus nucleoproteins for the assessment of molecular genetic mechanisms leading to new phylogenetic virus lineages. AB - The nucleoprotein (NP) gene of influenza A viruses is decisive for separating two large individually evolving reservoirs in birds and humans. A phylogenetic analysis of the NP gene revealed that all mammalian influenza viruses originated- directly or indirectly--from an avian ancestor. The stable introduction of an avian influenza A virus into a mammalian species seems to be a relatively rare event, the latest one occurred in 1979 when such an avian virus was introduced into pigs in Northern Europe which gave rise to a new lineage. At least two concomitant events are required for such a new and stable introduction: (1) The new species has to become infected, and (2) a mutation in the polymerase complex has to establish a labile variant, which is prone to provide a large number of different variants, from which some can adapt rapidly to the new host (or to any unusual environments). Since such mutator mutations might be advantageous only during stress periods, variants with a less error prone polymerase might emerge again after adaptation. Examples for such fluctuations in terms of mutational and evolutionary rates are discussed in this brief review. PMID- 8347077 TI - A low oncogenic variant of Friend murine leukemia virus with strong immunosuppressive properties. AB - Friend leukemia complex (FLC) is known to induce immunosuppression but the use of FLC in studies of immune cells function is disadvantageous since the immunosuppression always is accompanied by an acute erythroleukemia. To obtain immunosuppressive variants of FLC with reduced leukemogenic potential, we isolated T-helper cells from FLC infected mice, and passed lysates of the cells to recipient uninfected mice. A group of these mice developed a condition distinct from the disease induced by FLC. A viral stock prepared from these mice, designated Fd-MIV for friend derived murine immunodeficiency virus, induced a profound suppression of the primary antibody response without acute transformation in adult NMRI mice. Terminally a wasting disease with weight loss, atrophy of the thymus and lymph nodes and renal disease was observed in some mice. Analysis of viral DNA and RNA from infected NIH 3T3 cells showed that Fd MIV contained at least two viral components, a 8.4 kb friend murine leukemia virus (F-MuLV) and a 7.4 kb mink cell focus (MCF)/xenotropic virus related genome. The 7.4 kb genome was not detected in Fd-MIV infected, immunocompromised mice indicating that the 8.4 kb genome might be responsible for the disease. PMID- 8347078 TI - Infection studies with canine distemper virus in harbour seals. AB - Infection studies in harbour seal (Phoca vitulina) were conducted with the Snyder Hill strain of canine distemper virus (CDV) that is virulent for dog and mink. The inoculated seals showed clinical symptoms which were to some degree similar to those observed in CDV infections of sensitive species of carnivores. Viral replication in lymphoid cells was followed by an extended period of immunosuppression. The results did not provide conclusive evidence for viral replication in surface epithelia of seals, and accordingly no spread of the infection to contact seals and mink was demonstrated. The pathogenicity of the infection did not increase upon a second viral passage in seal. The serological data showed that CDV-infected seals mounted an early virus specific antibody response. Overall, the results indicated that the harbour seal was not especially sensitive to CDV infection. The differences in the in vivo biological properties of CDV and PDV add to the distinction between these viruses at the genomic and antigenic levels. PMID- 8347080 TI - The intestine is a site of passage for potato leafroll virus from the gut lumen into the haemocoel in the aphid vector, Myzus persicae Sulz. AB - Four detection techniques, three of which gave reliable identification of the virus particles, were used to locate potato leafroll virus (PLRV) in the alimentary canal of its main aphid vector, Myzus persicae Sulz: immunofluorescence on cryostat sections, conventional transmission electron microscopy on ultrathin sections and immune electron microscopy with gold labeling, either prior to or after fixation-embedding. Each method clearly showed the presence of the virus in the intestine epithelium and its absence in cells of the other parts of the alimentary canal. Under the experimental conditions used, the intestinal cells seemed to be the pathway for PLRV transport from the gut lumen into the haemocoel. Electron microscopy examinations showed many virus particles close to the apical plasmalemma of the epithelial cells in the gut lumen of the intestine. Other particles were seen in shallow pit-like regions or surrounded by coated vesicles in the apical part of these cells. Thus the virus particles seemed to enter the epithelial cells of the intestine by a mechanism of endocytosis. In the cytoplasm of these cells, virions were also frequently observed in isolated--or more often aggregated--tubular vesicles. The latter could be involved in PLRV transport through the cell since they were observed fusing with different cell organelles. A few viral particles were also detected in lysosomes as well as in multivesicular bodies. Virus particles were observed between the plasmalemma and basal lamina of the intestine cells but not in the haemocoel, where probably they were quickly dispersed. Our results are discussed in relation to other reports which have shown hindgut and stomach as sites of passage from the gut lumen into the aphid's body cavity for PLRV and other circulative viruses. PMID- 8347082 TI - Parsnip yellow fleck and rice tungro spherical viruses resemble picornaviruses and represent two genera in a proposed new plant picornavirus family (Sequiviridae). AB - Parsnip yellow fleck and rice tungro spherical viruses, with monopartite ss RNA genomes, resemble picornaviruses in the polymerase and NTP-binding domains of their encoded polyproteins. Though in separate genera, they may comprise a new family. PMID- 8347081 TI - Productive expression state confers resistance of human immunodeficiency virus (HIV)-2-infected lymphoma cells against superinfection by HIV-1. AB - In the past, positive as well as negative results pertaining to HIV-1/HIV2 interference have been obtained. Therefore, in the present study attention was paid to the viral expression state of preinfected cells at the time of exposure to secondary virus. A clonal HIV-2 infected HUT-78 cell line was derived by endpoint dilution and subsequently inoculated with cell-free HIV-1. Superinfection with HIV-1 was ruled out by Western blot and PCR analysis. The chronically HIV-2 infected cells used for these studies showed a highly productive expression state, as evidenced by immunoperoxidase staining (IPS), Western blot profile and levels of reverse transcriptase (RT) activity. We discuss several mechanisms of interference in productively infected cells, which may confer resistance to superinfection with secondary virus. PMID- 8347079 TI - Taxonomic relationships between distinct potato virus Y isolates based on detailed comparisons of the viral coat proteins and 3'-nontranslated regions. AB - Detailed comparisons were made of the sequences of the coat protein (CP) cistrons and 3'-nontranslated regions (3'-NTR) of 21 (geographically) distinct isolates of potato virus Y (PVY) and a virus isolate initially described as pepper mottle virus (PepMoV). Multiple sequence alignments and phylogenetic relationships based on these alignments resulted into a subgrouping of virus isolates which largely corresponded with the historical strain differentiation based on biological criteria as host range, symptomatology and serology. Virus isolates belonging to the same subgroup shared a number of characteristic CP amino acid and 3'-NTR nucleotide residues indicating that, by using sequences from the 3'-terminal region of the potyvirus genome, a distinction could be made between different isolates of one virus species as well as between different virus species. RNA secondary structure analysis of the 3'-NTR of twelve PVY isolates revealed four major stem-loop structures of which, surprisingly, the loop sequences gave a similar clustering of isolates as resulting from the overall comparisons of CP and 3'-NTR sequences. This implies a biological significance of these structural elements. PMID- 8347083 TI - Comparative analysis of the NS 1 gene sequences of dengue-1 viruses prototype Hawaii strain and Thai isolate TH-Sman, and determination of the intratypic variation of NS 1 protein among dengue-1 viruses. AB - In view of a previous report on significant antigenic and biophysical differences between the purified soluble complement-fixing antigens of dengue-1 virus strains Hawaii and TH-Sman, the NS 1 genes of both virus isolates were cloned, sequenced, and compared in an attempt to define the genetic basis for the observed differences. Sequence comparison revealed ten encoded amino acid differences between the NS 1 genes of both viruses. Three of these amino acid differences, which are associated with a change in charge distribution, are clustered within the major antigenic region previously defined by studies of recombinant dengue-1 NS 1 protein expressed in E. coli. In parallel, the NS 1 sequences of both Hawaii and TH-Sman isolates were also aligned and compared with two other published dengue-1 NS 1 protein sequences to determine the intratypic variation of dengue-1 NS 1 antigen. Pairwise comparisons between the encoded amino acid sequences revealed a variability of 1.1% to 3.1% difference in the NS 1 protein among dengue-1 strains, which is comparable to that reported for dengue-1 envelope protein (0.2% to 3.6% difference) but less than that of dengue-2 NS 1 protein (0.6% to 7.4% difference). PMID- 8347084 TI - Characterization of monoclonal antibodies to bovine enteric coronavirus and antigenic variability among Quebec isolates. AB - Twenty monoclonal antibodies (MAbs) were prepared against the Mebus strain of bovine enteric coronavirus, 14 of them reacting with the peplomeric S (gp 100) glycoprotein. Competition binding assays allowed the definition of at least 4 distinct antigenic domains for the S glycoprotein, designated as A, B, C, and D; epitopes associated to neutralizing activity being located in sites A, B, and C. One MAb directed to the hemagglutinin HE (gp 140/gp 65) glycoprotein inhibited the hemagglutinating activity of the virus, but had no neutralizing activity. Comparison of Quebec enteropathogenic BCV isolates using polyclonal antiserum and MAbs directed to the S glycoprotein confirmed their close antigenic relationship, but also revealed the occurrence of at least three distinct antigenic subgroups. Antigenic domain D was highly conserved among BCV isolates, as well as non neutralizing epitopes assigned to antigenic domains A and C. The Minnesota strain of turkey enteric coronavirus could be distinguished from BCV isolates by MAbs directed to epitopes of antigenic domain C, whereas human coronavirus HCV-OC 43 could be distinguished by MAbs directed to epitopes of antigenic domain A. The porcine hemagglutinating encephalomyelitis virus could be distinguished from the other hemagglutinating coronaviruses by neutralizing epitopes located on antigenic domains A, B, and C. PMID- 8347085 TI - Watermelon mosaic virus-Morocco is a distinct potyvirus. AB - The relationship of the Morocco isolate of watermelon mosaic virus (WMV) to WMV2, soybean mosaic virus (a virus closely related to WMV2) and the W strain of papaya ringspot virus (PRSV-W), formerly WMV1, was examined by comparing tryptic peptide profiles using high performance liquid chromatography. The profiles indicated that the coat protein sequence of WMV-Morocco differed substantially from those of the other potyviruses. This conclusion was supported by sequence data from five tryptic peptides from the coat protein of WMV-Morocco, which showed only 61 68% identity to equivalent sequences in PRSV-W, WMV2 and zucchini yellow mosaic, another potyvirus infecting cucurbits. Based on the above data, and on known correlations between coat protein sequence similarities and potyvirus relationship, it is concluded that WMV-Morocco should be regarded as a distinct potyvirus. PMID- 8347086 TI - The skin, tongue, and brain as favorable organs for hog cholera diagnosis by immunofluorescence. AB - Hog cholera virus antigens were found densely distributed in skin and tongue of pigs experimentally infected with hog cholera virus. The finding described here warrants the usage of ear biopsies for hog cholera diagnosis on a herd basis. PMID- 8347087 TI - Proposed classification of the bipartite-genomed raspberry bushy dwarf idaeovirus, with tripartite-genomed viruses in the family Bromoviridae. AB - Raspberry bushy dwarf virus (RBDV) has an unusual combination of properties and has been classified as the sole member of a new plant virus genus, for which the name idaeovirus has been proposed. Particles of RBDV resemble those of ilarviruses (family Bromoviridae) in appearance and in being transmitted in association with pollen. RBDV has two genomic RNA species, RNA-1 (5,449 nt) and RNA-2 (2,231 nt). The particles also contain RNA-3 (946 nt), a subgenomic monocistronic coat protein mRNA which is derived from the 3' end of the bicistronic RNA-2. The single 190 K protein encoded by RNA-1 contains methyltransferase, helicase and polymerase domains. Evolutionary distance data obtained from multiple alignments of the amino acid sequence of the RBDV 190 K protein and corresponding proteins with replicative function from other plant viruses suggest that the closest affinities of RBDV are with the tripartite genomed viruses in the family Bromoviridae. We propose that the genus idaeovirus be included in the family Bromoviridae. PMID- 8347088 TI - [A study of sensitization and symptoms in adult asthmatics who keep cat and dog]. AB - We studied hypersensitivity to cats and dogs in three hundred adult asthmatics who kept them. Some findings were noted as follows. 1) The mean duration for which cats were kept was 6.2 +/- 10.1 (1 S.D.) years and that for dogs was 4.2 +/ 9.6 (1 S.D.) years. 2) The positive rate in intradermal tests to dog dander was 7% and to cat hair-epithelium 32%. The positive RAST (score > or = 2) rate to cat epithelium was 36.1%, to dog dander 31.6% and to dog epithelium 7.3% respectively. 3) Eleven to 18% of the dog keepers and 23 to 36% of the cat keepers whose RAST score were positive were aware of the relationship between pets and asthma, specifically concerning eye and nose symptoms. 4) Thirty percent of the cat and dog keepers had become sensitized to them after keeping them for under one year. The positive RAST rate was unchanged in those who kept Japanese native dogs but increased in those who kept foreign breeds after 3 to 6 years. The rate of sensitization rate to cats tended to increase along with the period for which they were kept. 5) Dog dander RAST scores among the foreign breed keepers were significantly higher than those among the native dog keepers. If the dog breed was the same, the RAST score was not higher if the dog was kept indoors than if it was kept outdoors. We concluded that a possible reason why the RAST scores were higher among those who kept foreign breeds was that foreign breeds have stronger allergenicity. PMID- 8347089 TI - [Clinical study of patients with nocturnal asthmatic attacks admitted to an emergency room]. AB - Over the periods of a year, we studied the patients who were admitted to the emergency room at our hospital at night with asthmatic attacks. From July 1991 to June 1992, 10,932 patients were admitted to the internal department of our emergency room, 707 (6.5%) of them because of asthmatic attacks. These 707 consisted of 364 patients (51.5%) with mild attacks, 242 (34.2%) with moderate attacks and 101 (14.3%) with severe attacks according to Mitsui's score. Most patients admitted before 23:00 and after 5:00, but more patients with severe attacks were admitted around midnight. A large part of the patients with moderate or severe attacks had chronic hypoxemia, and more than half of the patients' serum theophylline concentration was under the therapeutic rate. More than half patients were treated within 5 minutes. But within those who were not, 6 patients with mild attacks on admission needed hospitalization later. For prevention of life threatening attack, we should regard it as an important problem to follow up the patients who don't come to the hospital in the daytime in spite of frequent visits to the emergency room at night. PMID- 8347090 TI - [Study of serum phospholipase A2 activity in bronchial asthmatic patients]. AB - We examined serum PLA2, lipids and platelets in 133 bronchial asthma patients who had not taken any glucocorticoids. Serum PLA2 was measured by radioimmunoassay. Serum PLA2 activity in the bronchial asthma patients was 384.2 +/- 114.7 (pmol/ml/min), and in the control group (healthy subjects) it was 271.7 +/- 53.9; this is a statistically significant difference (p < 0.01). Serum PLA2 of the mixed type was higher than that of the atopic type (p < 0.05) with respect to age, those subjects in their 60s showed statistically higher serum PLA2 values than those in their 20s and 30s (p < 0.05). The serum PLA2 level was statistically higher in a patient with an attack (409.1 +/- 113.9) than without an attack (342.6 +/- 94.3) (p < 0.05). However, there was no significant difference in lipid and platelet levels according to attack status. In conclusion, the serum PLA2 level is not only higher in asthma patients with attacks, but is also higher in asthma patients without attacks when compared to the control group. Therefore, the measurement of serum PLA2 is significant in predicting attacks. PMID- 8347091 TI - [IgE, IgG1 and IgG4 antibodies against bodily and fecal extracts of Dermatophagoides farinae]. AB - IgE, IgG1 and IgG4 antibodies against bodily (Dfb) and fecal (Dff) extracts of Dermatophagoides farinae (Df) were measured by enzyme linked immunosorbent assay (ELISA) in 33 asthmatic patients (AP), 27 healthy control subjects (HCS) and clinically healthy subjects with mite allergy (HS-MA) shown by positive skin reactions to house dust. Serum total IgE measured by radioimmunosorbent test, and IgE against Df was measured by the CAP system simultaneously. AP showed the highest mean value of total IgE and IgE against Df, Dfb and Dff. HS-MA showed the second highest value and HCS showed the lowest one. There were significant differences among these 3 groups. AP showed a significantly higher mean value of IgG1 and IgG4 than the other 2 groups. However, there was no significant difference between HS-MA and HCS. Antibody titers against Dfb and Dff correlated well. IgE, IgG1 and IgG4 titers obtained by ELISA also correlated with each other well. However, the results from the CAP system and IgE-ELISA did not agree in some cases indicating character differences between the CAP system and ELISA. In AP, the CAP system results agreed with those of ELISA. In HS-MA, however, many cases exhibited negative reactions to IgE-ELISA in spite of exhibiting positive reactions in the CAP system. PMID- 8347092 TI - [Immunological and physicochemical properties of Cry j II, the second major allergen of Japanese cedar pollen (Cryptomeria japonica)]. AB - Cry j II, the second major allergen of Japanese cedar (sugi, Cryptomeria japonica) pollen was examined for the allergenicity by intradermal test and RAST. Nineteen of the 25 allergic patients examined, showed positive reaction to the Cry j II. Contents of Cry j II in the extracts of the pollen collected in various regions from 1977 to 1991 showed yearly variation ranging from 2.9 to 14 mg/100 g pollen, whereas the amount of Cry j I in the extract was comparatively stable at about 35 mg/100 g pollen. Physicochemical treatments of Cry j I and Cry j II suggested that specific human IgE antibodies and some mAbs bind to conformational epitopes which are denatured and destroyed by certain treatments. PMID- 8347093 TI - [The usefulness and limitations of the radioallergosorbent test in diagnosing food allergy in atopic dermatitis]. AB - To clarify the diagnostic value of the radioallergosorbent test (RAST), the relationship between RAST and the oral food challenge test was evaluated. 263 children with atopic dermatitis were challenged by egg, cow's milk or soy bean after their skin manifestations had been improved by elimination diet and environmental control. Of 200 cases with negative RAST results for egg white, 108 cases (54.0%) showed no reaction in egg challenge tests. However, 65 cases (31.5%) had non-immediate reactions, while 29 cases (14.5%) had immediate reactions (within 2 hours of challenge). Of 16 cases with RAST score of 1 for egg white, 11 cases (68.8%) had non-immediate reactions and 2 cases (12.5%) had immediate reactions in egg challenge tests. Of 19 cases with RAST scores of 2 for egg white, 2 cases (10.5%) had no reaction, 6 cases (31.6%) had non-immediate reactions and 11 cases (57.9%) had immediate reactions in egg challenge tests. Of 21 cases with RAST scores of 3 for egg white, 1 case (4.8%) had no reaction, 3 cases (14.3%) had non-immediate reactions and 17 cases (81.0%) had immediate reactions in egg challenge tests. All 7 cases with RAST scores of 4 for egg white had immediate reactions in egg challenge tests. Almost the same relationship between RAST and challenge tests were found in test using cow's milk or soy bean. In conclusion, false negative results were seen in 46.0% of RAST for egg white, 51.7% of RAST for cow's milk and 26.9% of RAST for soy bean.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347094 TI - [Skin reaction(s) to culture supernatant(s) from Dermatophagoides farinae (Df) stimulated lymphocytes, and their correlation with Df-induced interleukin 2 responsiveness by lymphocytes from patients with bronchial asthma]. AB - To investigate the inflammatory function of Dermatophagoides farinae (Df) activated lymphocytes, supernatants from cultures of the lymphocytes were intracutaneously injected into donors' forearms. Injection of the supernatants of Df-stimulated lymphocytes from mite-sensitized atopic individuals with such diseases as bronchial asthma induced a profound inflammatory reaction in the autologous skin, characterized by erythema extending more than 15 mm in mean diameter and edema. The inflammation was at its peak after approximately 20 min, which was followed by gradually re-growing erythema lasting for as long as 24 hours after injection. Supernatants of unstimulated lymphocytes were also capable of inducing the same reaction, indicating the presence of in vivo activated lymphocytes, although the extent of the response was always smaller. The induced response in normal individuals was erythema of less than 15 mm in mean diameter. The supernatants obtained from cultures at 4 degrees C failed to induce such inflammation. The culture supernatants of ovalbumin-restimulated lymphocytes were also incapable of augmenting the response. The combined data show that the production of inflammatory response-inducing factor(s) from Df-stimulated lymphocytes was antigen specific. Significant skin reactions was correlated with the IL2 responsiveness of Df-stimulated lymphocytes. The skin reaction induced by factor(s) derived from Df-stimulated lymphocytes, which might be similar to the bronchial hyperreactivity of patients with bronchial asthma. The in vitro assay for Df-induced IL2 responsiveness by lymphocytes might reflect the in vitro immediate, late and/or delayed type hypersensitivity. PMID- 8347095 TI - The dysfunction of peripheral blood dendritic cells in patients with mixed connective tissue disease. AB - The morphological findings and functions of peripheral blood dendritic cells (DC) from patients with mixed connective tissue disease (MCTD) were compared with those of DC from normal subjects. DC from both groups possessed typical dendritic processes and showed HLA-DR antigens and C3bi receptor. The autologous mixed lymphocyte reaction (MLR) and autologous concanavalin A (Con A)-induced T cell proliferation using DC as stimulating cells and accessory cells were significantly depressed in patients with MCTD. In the allogeneic MLR and allogeneic Con A responses, DC from patients with MCTD were poorer stimulating cells and accessory cells. The dysfunction of DC also, as one of the various immune abnormalities, must play a role in the appearance of clinical features. PMID- 8347096 TI - Lung functions and chest radiographs in shipyard workers exposed to asbestos. AB - Lung functions and diffusing capacity for carbon monoxide were examined in 299 shipyard workers occupationally exposed to asbestos, among whom there was an equal number of smokers and non-smokers. The workers were classified into groups according to the lung fibrosis profusion and the length and width of the pleural plaques in accordance with the 1980 ILO International Classifications of Pneumoconioses. With regard to the profusion of the parenchyma, workers classified in category 2 (subcategories 2/1 and 2/2) had significantly lower FVC and FEV1 values than the workers in categories 0 (P < 0.01) and 1 (P < 0.05). With an increase in the category of profusion there was a trend towards a fall in mean MEF25, MEF50 and MEF75 values, but it was not significant. Diffusing capacity for carbon monoxide was identical for all categories. There were no significant differences between the workers without pleural plaques and those with visible plaques in respect to lung function values. With an increase in the length and width of the plaques FVC, FEV1, MEF25 and MEF75 values tended to become lower. The results demonstrate that the changes detected on the radiographs of the lungs and pleura are the early indicators of possible asbestos disease in shipyard workers. PMID- 8347097 TI - Thoron activity level and radon measurement by a nuclear track detector. AB - Radon activity concentrations in the air were measured with LR-115 nuclear track detectors at three locations in Osijek. The respective equilibrium factors and the effective dose equivalents were determined. Indoor concentrations were from 9.8 to 58.2 Bq m-3 and relative errors of the track etching method were near 19 per cent. The indoor alpha potential energy of the radon and thoron progenies was measured with an ISD detector. Independent measurements, performed with a Radhome semiconductor detector, showed that the indoor thoron concentration was nearly 20 per cent of the radon one. PMID- 8347098 TI - A selection of biological indicators in occupational exposure to toluene and xylene. AB - Results of a comparative study of occupational exposure to toluene and xylene are presented. The study was carried out in a group of 24 workers from a paint factory and aimed to determine the most appropriate exposure indicators for use in biological monitoring. Measurements included toluene and xylene in blood and their metabolites in urine. Toluene in blood proved to be the best indicator of toluene exposure, and both xylene in blood and its only major metabolite methylhippuric acid in urine to be reliable indicators of xylene exposure. The validity of hippuric acid and o-cresol as toluene exposure indicators has not been confirmed. PMID- 8347099 TI - Some ecological characteristics of a brook water. AB - The water of a mountain brook was analysed and selected water quality parameters were determined. The pristine mountain brook water contained the smallest numbers of microorganisms whereas in the polluted water body downstream, the values of chemical oxygen demand, biochemical oxygen demand after five days and the count of specific indicator organisms (faecal coliforms) were increased. PMID- 8347101 TI - [Protection of the Croatian population from accidental radioactive contamination of the food chain]. AB - The paper indicates the importance of investigating radionuclide translocation in the human food chain, and the contribution of selected food components in total exposure of the population after accidental radioactive contamination. Data on radioactive contamination and risk assessment of the Croatian population after the Chernobyl nuclear accident are given and possibilities of decontamination of food chain components are discussed. Literature data on radionuclide removal from the human food chain are compared to the results of own investigations. Emphasis is placed on biologically most important radionuclides, 131I, 90Sr, 137Cs, and the most effective means of protection are sought. The preventive measures following a nuclear accident should be based on the cost-benefit principle i.e. the damage from applying radiation protection measures should not exceed the benefit from possible dose reduction. PMID- 8347100 TI - [Immunologic reactions, respiratory symptoms and ventilatory capacity in jute and sisal textile workers]. AB - Allergic reactions in relation to respiratory symptoms and ventilatory capacity were studied in 41 textile workers employed in the processing of jute and sisal. Only 5.0% of the jute workers and 9.5% of the sisal workers demonstrated positive skin reactions to jute or sisal allergens. Increased IgE was found in 9.8% of the textile workers. Among 35 control workers 11.4% reacted with a positive skin reaction to the jute or sisal allergen and 2.9% had increased IgE. Chronic respiratory symptoms as well as changes in ventilatory capacity were found in textile workers with positive and negative skin tests. Our data suggest that immunological reactions are not likely to be responsible for the development of respiratory impairment in textile workers exposed to jute and sisal dust. PMID- 8347102 TI - Delayed effects of lead on the kidney--factor analysis. AB - A late, i.e. delayed, effect of lead on kidney function and blood pressure was studied in 23 workers with a history of occupational lead poisoning. Twenty lead exposed workers with no known history of lead poisoning were a positive control. Four important factors out of 11 combined variables derived from 22 single variables were identified by factor analysis. The first factor comprised the variables kidney function, blood pressure, age, duration of lead exposure and the number of previous lead poisonings. The second factor comprised the variables duration of lead exposure and biological indicators of lead exposure. The third factor correlated the frequency of previous lead poisonings with the renal blood flow, erythrocytic protoporphyrin and age. The fourth factor comprised the variables length of work service, creatinine clearance and erythrocytic protoporphyrin. The results confirm the presence of the adverse late effect of previous occupational lead poisoning on kidney function regardless of treatment. The phenomenon is not a single event but a complex interplay of past lead poisoning, duration of exposure to lead, "normal" age effect on an increase in systolic and diastolic blood pressure and blood creatinine and a decrease in renal function as revealed by decreased creatinine clearance and a slow down in renal flow time. The complexity of dealing with the confounding variable of age and lack of appropriate classification of renal function impairment may account for the conflicting results of chronic lead effect upon kidney function in the past. The kidney appears to be a critical target organ, reflecting the total lead body burden in chronic lead exposure and poisoning. Therefore monitoring of kidney function in lead exposed workers needs to be mandatory. PMID- 8347103 TI - [Plasma amino acid levels in alcoholics]. AB - Plasma aromatic amino acid (AAA) and branched-chain amino acid (BCAA) concentrations were determined in 197 alcoholics. The BCAA/AAA molar ratio in patients with alcohol withdrawal symptoms was compared with the ratio in patients without such symptoms. The BCAA/AAA molar ratio in patients with emotional disturbance or with transient hallucination was significantly lower than that in patients without these symptoms. The BCAA/AAA molar ratio tended to be lower in patients with alcohol withdrawal convulsion or with delirium tremens as compared to patients without such symptoms. The BCAA/AAA molar ratio had a negative correlation with plasma total bilirubin and LDH and had a positive correlation with plasma choline esterase and albumin. Oral administration of amino acid preparations (Aminoleban EN) to the patients elevated the BCAA/AAA molar ratio and normalized liver function. These results indicate that abnormalities of amino acid metabolism caused by liver damage in alcohol dependence may have an important role in the pathogenesis of alcohol withdrawal syndrome. PMID- 8347104 TI - [Effect of ethanol on isometric tone of aorta from guinea pig]. AB - Using aortic strips isolated from guinea pig, effects of ethanol on vascular smooth muscle tone were studied. Low concentrations (5, 50, 100 mM) of ethanol potentiated norepinephrine and serotonin-induced contractions, but not KCl induced one. Ethanol (100 mM) potentiated calcium-induced contraction in the presence of norepinephrine, but not that in the presence of KCl. Ethanol (100 mM) showed no effects on norepinephrine-induced contraction in the calcium-free medium. Ethanol (100 mM) augmented 45Ca uptake stimulated with norepinephrine, but not that with KCl. Ethanol at the higher concentration of 600 mM by itself induced contraction, which was inhibited by trifluoperazine or in the calcium free medium, but not by phentolamine, diphenhydramine, methysergide, indomethacin or nifedipine. Ethanol (600 mM) directly increased 45Ca uptake, which was not affected by nifedipine. These findings indicate that the low concentrations of ethanol potentiate receptor-mediated vascular smooth muscle contraction and the higher concentration of ethanol directly contracts it via facilitation of transmembranous calcium influx. PMID- 8347105 TI - [Alcohol and sudden death: a survey on alcohol-related deaths at tokyo Metropolitan Medical Examiner's Office (1989)]. AB - Seven thousand three hundred seventy-six sudden or violent manner of deaths were inspected or autopsied at Tokyo Metropolitan Medical Examiner's Office in 1989. Out of these victims, 693 (9.4%) victims were regarded as heavy drinkers on the basis of the drinking habits and the autopsy reports and 196 (2.7%) victims without past problem drinking were thought to be drunk at death from the family statements or the blood alcohol analysis. The total 889 (12.1%) alcohol-related cases (autopsy was performed on the 489 cases) were studied from epidemiological and etiological viewpoints. The average age of the alcohol-related victims (male: 811, female: 78) was 52 +/- 11 years. In middle-aged (45-54 years) men, 34% of the all sudden or violent deaths were alcohol-related. About half of the alcohol related victims were living alone and jobless and they often died at home, particularly in the bed. In the alcohol-related victims, the blood alcohol concentration (BAC) analysis revealed that the average BAC of female was significantly higher than that of male. (2.12 +/- 1.73 mg/ml vs. 1.33 +/- 1.75, P < 0.01). This difference may be associated with sex difference in ethanol metabolism, body composition and drinking habits. Among the major causes of the alcohol-related deaths, alcoholic liver diseases accounted for 226 (25%), gastro intestinal bleedings for 115 (13%), cardiovascular diseases for 105 (12%) and violent deaths (e.g., acute alcohol intoxication, falls, traffic accidents, suicide) for 329 (37%). By histopathological examination of the liver, about 30% of the alcoholic liver disease cases showed mainly fatty metamorphosis and 48% showed liver cirrhosis. Only 12% of the cirrhotics had either jaundice or ascites, suggesting hepatic failure. Alcoholic cardiomyopathy was suspected in only 11 cases. In conclusion, many people, particularly middle-aged men, lose their lives due to heavy drinking and there are many pathologically unexplainable sudden deaths of alcoholics. PMID- 8347106 TI - Occupational health and safety learning on the job. PMID- 8347107 TI - Sorrow and strength. PMID- 8347108 TI - What did we learn from the federal election? PMID- 8347109 TI - A message to enrolled nurses covered by federal awards. PMID- 8347111 TI - Consent issues in psychiatric nursing. PMID- 8347110 TI - Health care economics. Part 2: The Australian health care "jigsaw". AB - In this article we look at how the health care industry is organised in Australia and make some international comparisons. First, we examine how Australia has reached the present, rather confusing set of arrangements--what the Macklin inquiry has called the health "jigsaw". Then we outline the current arrangements- how responsibilities are divided between local, state and federal governments; and the contribution of the private sector. Finally, we present international data to provide some comparative perspective on Australia's health care arrangements. PMID- 8347112 TI - Putting stress into words: health, linguistic, and therapeutic implications. AB - When individuals are asked to write or talk about personally upsetting experiences, significant improvements in physical health are found. Analyses of subjects' writing about traumas indicate that those whose health improves most tend to use a higher proportion of negative emotion words than positive emotion words. Independent of verbal emotion expression, the increasing use of insight, causal, and associated cognitive words over several days of writing is linked to health improvement. That is, the construction of a coherent story together with the expression of negative emotions work together in therapeutic writing. Evidence of these processes are also seen in specific links between word production and immediate autonomic nervous system activity. Implications for therapy and for considering the mind and body as fluid, dynamic systems are discussed. PMID- 8347113 TI - The effects of distraction during exposure to phobic stimuli. AB - Theoretical conceptualizations regarding the role of attentional focus during exposure-based treatments for fear and anxiety suggest that distraction interferes with the mechanisms required for fear reduction, typically by preventing emotional and/or cognitive processing of the phobic stimulus and response. The present discussion reviews the current literature and demonstrates the paucity of empirical evidence supporting such notions. Seemingly conflicting findings are integrated upon close examination of the various qualitative dimensions of the distracters employed. These characteristics, which differed substantially across studies, include the nature of the attentional demand posed by the distracter (e.g. cognitive vs sensory demand) as well as the distracter's affective quality (e.g. neutral vs relaxing). The effects of differing dimensions of distraction on fear reduction, in addition to interaction with aspects of the exposure situation, are discussed. The need for further investigation of the qualitative dimensions of distraction, including their operational specification, is recognized. Finally, recommendations for future research are made. PMID- 8347114 TI - Effects of anxiety and awareness on colour-identification latencies for emotional words. AB - A modified Stroop task was used to examine the interference effects of subliminal and supraliminal emotional words on the colour-identification latencies of high and low trait anxious subjects. The subjects were randomly allocated to either an anxiety or relaxation mood induction procedure (MIP) before the modified Stroop task. Increased trait anxiety was associated with relatively greater interference in colour-identification latencies for subliminal threat stimuli. Reduced state anxiety was associated with relatively more interference of subliminal positive stimuli (mood-congruent effect), but also with greater interference of supraliminal threat stimuli (mood-incongruent effect). The results suggest that mood-congruent effects may be mediated by automatic processes, whereas controlled processes may give rise to mood-incongruent effects. PMID- 8347115 TI - Is optimism heritable? A study of twins. AB - Is optimism heritable? We gave the Attributional Style Questionnaire (ASQ), a measure of optimism, to 115 monozygotic twin pairs (MZ) and 27 dizygotic twin pairs (DZ). The intraclass correlations of the ASQ scores were 0.48 for MZ twins (P < 0.0001) and 0 for DZ twins. Though the sample size of DZ twins is small, these results suggest that there may be a substantial genetic effect on optimism. We speculate, however, that the mechanism for the transmission of this, and other complex personality traits, may be highly indirect. PMID- 8347116 TI - Habituation and dishabituation of male sexual arousal. AB - Sixteen men were tested under conditions where they viewed the same segment of erotic film on many occasions or engaged repeatedly in the same erotic fantasy. Decrements in penile tumescence and subjective sexual arousal over trials were accompanied by reports from Ss that they felt less absorbed in the events depicted in film or fantasy (and in the case of fantasy, that the images they formed became less vivid). Analysis of covariance showed that habituation (reduction in physiological and subjective measures of sexual arousal over trials) was less when allowance was made for the manner in which absorption (and in vividness of imagery in the case of fantasy) changed during erotic stimulation. Increases in sexual arousal when novel erotic stimulation was introduced following habituation, as well as the dishabituation found when the original stimulus was reinstated, also correlated with the extent absorption and vividness of imagery shifted under these conditions. The results are discussed with reference to whether habituation of male sexual arousal is mediated by changes that occur in absorption and other aspects of information processing during repeated erotic stimulation. PMID- 8347117 TI - Prospective associations among family form, family processes, and adolescents' alcohol and drug use. AB - The present study was designed to disentangle and define the unique contributions of family form and family processes to substance use and association with deviant peers among adolescents. Eighty adolescents and their mothers participated in the study; half were from divorced single-parent families and half were from families in which the parents were still married. Maternal assessments of interparental conflict and the quality of the mother-adolescent relationship were used to prospectively forecast adolescent reports of substance use and affiliation with deviant peers one year later. The results revealed that mother-adolescent conflict predicted adolescent alcohol use, and maternal acceptance-rejection predicted both drug use and affiliation with deviant peers. These findings support the hypothesis that family processes rather than family form forecast adolescents' substance use and deviant peer affiliation. Clinical implications of the findings are discussed. PMID- 8347118 TI - The representation of feared outcomes. AB - A list of negative outcomes (harmful events) was constructed to investigate the nature and organization of outcome concerns in anxiety. In Study 1, analysis of worry frequency ratings for the 116 negative outcomes revealed two major correlated factors corresponding to physical outcomes (harm or misfortune) and social outcomes (negative evaluation). These higher-order factors could be further subdivided into smaller discrete categories of related concerns. Ratings of worry frequency were higher for social outcomes. Trait anxiety was associated with both physical and social concerns, but stress and depression were primarily associated with social concerns. In Study 2, aversiveness ratings for the 116 negative outcomes followed the same physical-social organization and formed similar lower-order categories. Unlike the worry frequency ratings, aversiveness ratings were higher for physical than social categories, and did not correlate substantially with trait measures of depression, anxiety or stress. In Study 3, a short (24-item) negative outcome questionnaire was developed to discriminate between concerns about physical and social outcomes. The Physical Scale correlated substantially with the Anxiety Sensitivity Index (ASI) but not the Fear of Negative Evaluation (FNE), whereas the Social Scale correlated with the FNE but not the ASI. The Penn State Worry Questionnaire (PSWQ), which assesses worry frequency but not content, correlated only with the Social Scale. Implications for theories of normal and clinical anxiety are discussed. PMID- 8347119 TI - Verbalization and environmental cuing in thought suppression. AB - Research on thought suppression has yielded a morass of conflicting results. While some studies show that suppression of a thought results in a rebound effect (i.e. a heightened frequency of this thought later on), other studies failed to demonstrate this phenomenon. The first aim of the present study was to investigate whether the method used to study stream of consciousness (verbalization vs thinking silently) affects the report of target thoughts in a thought suppression experiment. Second, the claim that environmental cuing (i.e. distraction by directing attention towards external cues) is the mechanism behind the recurrence of suppressed items was examined. Results indicated that the method used to monitor stream of consciousness did not modulate the report of target thoughts: in fact, no rebound effect occurred. However, results did support the suggestion that heightened frequencies of suppressed material are related to environmental cuing. PMID- 8347120 TI - Arousal training for children suffering from nocturnal enuresis: a 2 1/2 year follow-up. AB - Arousal Training is a fast, simple, and effective form of bibliotherapy for nocturnal enuresis with non-clinical children between 6 and 12 years of age. The parents act as therapists. They reward the operant behavior-pattern following the urine alarm. The success rate is 98% (N = 41), which is significantly high when compared to the control conditions (79%, N = 86). There was a response rate of 100% and no drop-out from therapy. All parents (N = 127) completed and returned the record. The results of a follow-up of this bibliotherapy (N = 113) 2 1/2 years later are presented. The success rate of Arousal Training was still significantly higher (92% continent) when compared to the urine device with specific instructions (77%) and urine alarm only (72%). Arousal Training is the treatment of choice for non-clinical enuretic children between 6 and 12 years of age. PMID- 8347121 TI - The utilisation of working memory by worry. AB - Sixty-eight undergraduate students were randomly allocated to one of four task conditions and required to worry about a topic of importance to them while simultaneously performing the task to which they had been allocated. The tasks differed in their ability to interfere with worrying. Generation of random letters was the only task to interfere significantly with the ability to worry. There was a nonsignificant tendency for articulatory suppression to produce some interference with worrying while visuo-spatial tasks did not affect the ability to worry. There was no difference in results between self-reported worriers and non-worriers. The results seem to indicate that worry primarily utilises the phonological aspect of the central executive of working memory. PMID- 8347122 TI - Preservation of the rate and profile of xenobiotic metabolism in rat hepatocytes stored in liquid nitrogen. AB - A simple procedure for cryopreservation of rat hepatocytes that allows recovery of viable cells retaining activities of phase I and phase II drug metabolism equivalent to freshly isolated cells is described. The cooling process was initiated 30 min after incubation of freshly isolated hepatocytes at 37 degrees in Krebs-Ringer bicarbonate buffer containing 15 mM glucose to allow for metabolic equilibration. At the end of this period, hepatocyte suspensions were supplemented with 1.7% albumin, 13.3% dimethyl sulfoxide, and the synthetic buffers, 3-[N-morpholino]propanesulfonic acid (MOPS) and N-[2 hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] (HEPES). Hepatocytes were cooled in a stepwise manner to -196 degrees by holding the cells for 1 hr at -20 degrees and then for 1 hr at -70 degrees before transfer into liquid nitrogen. After thawing and removal of damaged cells by centrifugation in Percoll, the total recovery of viable hepatocytes subjected to freezing was about 42%. The contents of ATP, ADP, and AMP were not altered significantly in cells stored in liquid nitrogen. The metabolic competence of cryopreserved hepatocytes was further confirmed by their ability to synthesize urea from NH4Cl and ornithine at the same high rate that was observed in freshly isolated cells (693 +/- 68 and 740 +/- 68 nmol.mg dry wt-1 x hr-1, respectively). Similarly, cryopreservation did not affect drug-metabolizing systems as indicated by the metabolism of benzo[a]pyrene and 7-ethoxycoumarin, two model substrates. In both freshly isolated and cryopreserved hepatocytes, 7-ethoxycoumarin was O-deethylated to 7 hydroxycoumarin at essentially the same rates (8.66 +/- 0.75 and 8.25 +/- 0.53 nmol.mg dry wt-1.hr-1, respectively) and 7-hydroxycoumarin accumulated in hepatocyte suspensions almost exclusively in the conjugated form. The storage of hepatocytes in liquid nitrogen also did not affect the complex metabolism of benzo[a]pyrene to total oxygenated metabolites and, more importantly, to metabolites conjugated with glutathione, glucuronic acid, and sulfuric acid. Thus, cryopreserved hepatocytes represent a valid and convenient model to study drug biotransformation in intact cells. PMID- 8347123 TI - Metabolic activation of n-butyraldoxime by rat liver microsomal cytochrome P450. A requirement for the inhibition of aldehyde dehydrogenase. AB - n-Butyraldoxime (n-BO) is known to cause a disulfiram/ethanol-like reaction in humans, a manifestation of the inhibition of hepatic aldehyde dehydrogenase (AIDH). As with a number of other in vivo inhibitors of AIDH, n-BO does not inhibit purified AIDH in vitro, suggesting that a metabolite of n-BO is the actual inhibitor of this enzyme. In re-examination of the effect of n-BO on blood acetaldehyde levels following ethanol in the Sprague-Dawley rat, we found that pretreatment with substrates and/or inhibitors of cytochrome P450 blocked the n BO-induced rise in blood acetaldehyde in the following order of decreasing potency: 1-benzylimidazole (0.1 mmol/kg) > 3-amino-1,2,4-triazole (1.0 g/kg) > ethanol (3.0 g/kg) > phenobarbital (0.1% in the drinking water, 7 days) > SKF 525A (40 mg/kg). Rat liver microsomes were shown to catalyze the conversion of n BO to an active metabolite that inhibited yeast AIDH. This reaction was dependent on NADPH and molecular oxygen and was inhibited by CO and 1-benzylimidazole. Hydroxylamine, postulated by others to be a metabolite of n-BO, inhibited AIDH via a catalase-mediated reaction and not through an NADPH-supported microsome catalyzed reaction. Using GLC-mass spectrometry, 1-nitrobutane (an N-oxidation product) and butyronitrile (a dehydration product) were identified as metabolites from microsomal incubations of n-BO. However, neither of these metabolic products inhibited AIDH directly or in the presence of liver microsomes and NADPH. We conclude that another NADPH-dependent, cytochrome P450-catalyzed metabolic product of n-BO is responsible for the inhibition of AIDH by n-BO. PMID- 8347124 TI - An investigation into the formation of stable, protein-reactive and cytotoxic metabolites from tacrine in vitro. Studies with human and rat liver microsomes. AB - Tacrine (1,2,3,4-tetrahydro-9-aminoacridine hydrochloride; THA) is known to undergo extensive oxidative metabolism to a variety of mono- and dihydroxylated metabolites in animals and humans. The potential for tacrine to undergo metabolism to stable, protein-reactive and cytotoxic metabolites has been investigated in incubations with human and rat liver microsomes. Using lymphocytes as sensitive markers to quantify cytotoxicity, THA (50 microM) underwent NADPH-dependent bioactivation to a cytotoxic metabolite(s). NADPH dependent cytotoxicity in the presence of rat and human microsomes was 9.8 +/- 3.1% (P < 0.05 cf. -NADPH control) and 6.2 +/- 2.0% (P < 0.05 cf. -NADPH control), respectively. Stable and protein-reactive metabolites were also formed in microsomes from both species. These accounted for 28.2 +/- 12.7% and 1.22 +/- 0.79% of incubated radioactivity in human microsomes and 6.4 +/- 2.2% and 0.4 +/- 0.1% of incubated radioactivity in rat microsomes. In microsomes pooled from six human livers the NADPH-dependent cytotoxicity was 9.4 +/- 1.1%. Formation of stable and protein-reactive metabolites accounted for 29.2 +/- 2.3% and 1.2 +/- 1.0% of incubated radioactivity. Reduced glutathione (500 microM) completely blocked NADPH-dependent cytotoxicity and inhibited protein-reactive metabolite formation by 60% (P < 0.05). Ascorbic acid (500 microM) inhibited the generation of cytotoxic and protein-reactive metabolites by 75% (P < 0.05) and 35% (P < 0.05), respectively. Cyclohexene oxide was without effect. Human serum albumin was found to protect the lymphocytes against toxicity. In microsomes prepared from the livers of four donors known to have been smokers there were no significant differences in the generation of metabolites from THA compared with microsomes prepared from livers of non-smokers. Enoxacin, a specific inhibitor of cytochrome P450 1A2 significantly inhibited all routes of THA metabolism. We have therefore demonstrated that THA may be oxidatively metabolized to stable, protein reactive and cytotoxic metabolites in human and rat liver microsomes. A number of inhibitors may affect these process, whilst inhibition by enoxacin indicates a role for cytochrome P450 1A2 in THA metabolism. PMID- 8347125 TI - Cytochrome P450 in trypanosomatids. AB - Post-mitochondrial supernatant extracts prepared from bloodstream forms of Trypanosoma brucei brucei, T. cruzi epimastigotes, Leishmania donovani promastigotes and Crithidia fasciculata have been found to catalyse cytochrome P450-dependent reactions. Appreciable ethoxycoumarin deethylase and ethoxyresorufin deethylase activities were found in all of the above trypanosomatids, with T. cruzi epimastigotes having the highest activity (57.1 and 10.7 pmol/min/mg protein, respectively). In all four species these reactions were inhibited by the cytochrome P450 inhibitors carbon monoxide, proadifen and metyrapone. In contrast to rat liver microsomes, the trypanosomatid extracts showed no detectable pentoxyresorufin depentylase or pentamidine hydroxylase activity. Both C. fasciculata and T. b. brucei post-mitochondrial supernatants showed carbon monoxide difference spectra consistent with the presence of cytochrome P450 (9.6 and 6.3 pmol/mg protein, respectively). An additional hemoprotein which gave a carbon monoxide difference peak at 420 nm was also detected in C. fasciculata and T. b. brucei microsomes and C. fasciculata mitochondria. Subcellular fractionation of both early and late log C. fasciculata showed that the ethoxycoumarin deethylase activity was enriched in the microsomal fraction. PMID- 8347126 TI - Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. AB - Although L-carnitine has been reported to have protective effects against ammonia toxicity, conflicting results have also been presented and the mechanisms underlying the protection, if any, are not clear. In the present study, we examined the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Administration of ammonium acetate (15 mmol/kg) to mice caused seizures, elevation of blood ammonia and urea concentrations, and marked alterations of brain energy metabolites. Pretreatment with either L-carnitine, D carnitine or acetyl-L-carnitine reduced the frequency of the seizures, prolonged the time until the first fit, lowered the levels of ammonia in the blood and brain, and suppressed the alterations of brain energy metabolites caused by hyperammonemia. there was no significant difference between L- and D-carnitine in the potency to inhibit the seizures. In addition, there was no difference between the two chemicals in the potency to decrease the ammonia contents in the blood and brain, or to suppress the alterations of energy metabolites in the brain. When compared with L-carnitine, however, acetyl-L-carnitine better preserved ATP in the brain, while it lowered ammonia in the blood and brain less markedly. These results show that L-carnitine and its analogues do have the potential to suppress the neurotoxicity of ammonia. Moreover, the results suggest that the protective effects of carnitine against the toxicity of ammonia are systemic, that the action of acetyl-L-carnitine may differ from that of L- or D-carnitine, and that the "classical" function of carnitine is not the sole mechanism underlying the suppression of the neurotoxicity of ammonia. PMID- 8347127 TI - An unexpected pathway for the metabolic degradation of 1,3-dialkyl-3 acyltriazenes. AB - In the presence of NADPH, rat liver microsomes catalyzed the degradation of a series of 1,3-dialkyl-3-acyltriazenes, and the extent of the reaction was correlated with compound lipophilicity. In the case of two methylcarbamoyltriazenes, 1-(2-chloroethyl)-3-benzyl-3- (methylcarbamoyl)triazene (CBzM) and 1-(2-chloroethyl)-3-methyl-3-(methylcarbamoyl)triazene (CMM), microsomal metabolites were isolated. Identification of the CBzM metabolites as 1 (2-chloroethyl)-3-benzyl-3-(hydroxymethylcarbamoyl)triazene and 1-(2-chloroethyl 3-benzyl-3-carbamoyltriazine, and the CMM metabolite as 1-(2-chloroethyl)-3 methyl-3-(hydroxymethylcarbamoyl)triazene indicated that the first metabolic step involves hydroxylation of the methylcarbamoyl substituent. Detailed studies of the metabolism of CBzM indicated that the Km for the reaction was 84 microM, and that metabolism was more efficient if microsomes were prepared from male than from female rats. During prolonged incubation, the metabolites of CBzM were also degraded. The degradation of CBzM and its metabolites was inhibited by SKF-525A and metyrapone, suggesting the involvement of a cytochrome P450 isozyme, and supporting the hypothesis that the process is oxidative rather than hydrolytic in both cases. Metabolic oxidation represents an alternative pathway to chemical or enzymatic hydrolysis for the in vivo decomposition of (methylcarbamoyl)triazenes. This mechanism may ultimately explain the antitumor efficacy and low acute toxicity of selected compounds. PMID- 8347128 TI - Highly cooperative inhibition of acetylcholinesterase by pentachlorophenol in human erythrocytes. AB - Pentachlorophenol (PCP) inhibited acetylcholinesterase (AchE) activity in human erythrocyte membranes with high cooperativity. The Hill coefficient for the inhibition was 4-5 in "untreated" membranes. Differences in the temperature (13, 25 and 37 degrees) or treatment with 1% Triton X-100 did not clearly affect the cooperativity which, however, increased after the erythrocyte membranes were treated with 2-mercaptoethanol and iodoacetatic acid, suggesting that higher cooperativity in the inhibition of AchE by PCP may reflect conformational changes of AchE. Thus, PCP may be useful for the study of AchE in human erythrocytes. PMID- 8347129 TI - Mitomycin C stimulates the expression of human immunodeficiency virus long terminal repeat sequences in rat and human fibroblasts. AB - We have employed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) sequences of the human immunodeficiency virus-1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (CAT) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 into rat 208F and human MRCSV40TGR fibroblasts and obtained stable geneticin resistant RFBHIV1-1 and SVTGHIV1-1 cells, respectively. Both transfectant cells express CAT activity from the HIV LTR promoter. The response to the antineoplastic drug mitomycin C was studied on the LTR regulated CAT activity in both cell lines. It was found that mitomycin C at 10 micrograms/mL concentration stimulates the expression of CAT from the HIV LTR 77-fold in rat RFBHIV1-1 and 3.1-fold in human SVTGHIV1-1 cells. PMID- 8347131 TI - Ascorbate-dependent elevation of mRNA levels for cytochrome P450s induced by polychlorinated biphenyls. AB - Trichlorobiphenyl induced only CYP1A2 mRNA, while pentachlorobiphenyl induced both CYP1A2 and CYP2B1 mRNAs in rat liver. The mRNA levels for these P450s were elevated when ascorbic acid-deficient ODS rats (mutant rats with a hereditary osteogenic disorder) were fed a diet supplemented with ascorbic acid. The amount of CYP2B1 mRNA increased rapidly and reached a maximum level of approximately double within 24 hr of injection of pentachlorobiphenyl. Thereafter, the amount of its mRNA decreased to a steady level. This pattern was roughly paralleled by changes in the amount of CYP1A2 mRNA. PMID- 8347132 TI - The effect of 2-substituted thiazolidine-4(R)-carboxylic acids on non-protein sulphydryl levels and sulphurtransferase activities in mouse liver and brain. AB - 2-Substituted thiazolidine-4(R)-carboxylic acids (TD) were found to increase the concentration of non-protein sulphydryls (NPSH) and the activity of rhodanese (thiosulphate sulphurtransferase, EC 2.8.1.1) and 3-mercaptopyruvate sulphurtransferase (EC 2.8.1.2) in mouse liver. These properties suggest TDs are potentially hepatoprotective compounds. However TDs also cause depletion of NPSH in the mouse brain and this may be the reason for their toxic side effects on the central nervous system. PMID- 8347130 TI - Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. AB - The diterpenes andrographolide (I), andrographiside (II) and neoandrographolide (III) isolated from Andrographis paniculata were investigated for their protective effects on hepatotoxicity induced in mice by carbon tetrachloride or tert-butylhydroperoxide (tBHP) intoxication. Pretreatment of mice with the diterpenes (I, II & III; 100 mg/kg, i.p.) for 3 consecutive days produced significant reduction in malondialdehyde formation, reduced glutathione (GSH) depletion and enzymatic leakage of glutamic-pyruvate transaminase (GPT) and alkaline phosphatase (AP) in either group of the toxin-treated animals. A comparison with the known hepatoprotective agent silymarin revealed that I exhibited a lower protective potential than II and III, which were as effective as silymarin with respect to their effects on the formation of the degradation products of lipid peroxidation and release of GPT and AP in the serum. GSH status was returned to normal only by III. The greater protective activity of II and III could be due to their glucoside groups which may act as strong antioxidants. PMID- 8347133 TI - Quantitative determination of human aldose reductase by enzyme-linked immunosorbent assay. Immunoassay of human aldose reductase. AB - An antibody-sandwich enzyme-linked immunosorbent assay (ELISA) for evaluating tissue levels of aldose reductase was developed using a polyclonal antibody prepared against the recombinant enzyme expressed in a baculovirus system. The specificity of this antibody to aldose reductase was verified by immunoprecipitation, immunoblotting and ELISA. The polyclonal antibody did not crossreact with human aldehyde reductase, an enzyme in the same aldo-keto reductase family structurally and functionally related to aldose reductase. The sensitivity and specificity of this assay method enabled direct determination of aldose reductase level in various human tissues including the erythrocyte. The highest level of aldose reductase was detected in the kidney medulla among tissues investigated. More than a 2-fold variability in the erythrocyte aldose reductase was demonstrated among healthy individuals, indicating the heterogeneity of this enzyme expression in a human population. This assay system may be useful for direct measurement of the level of tissue aldose reductase in conjunction with the evaluation of the efficacy of aldose reductase inhibitors prescribed for the treatment of diabetic complications. PMID- 8347134 TI - Alterations in rat hepatic drug metabolism during pregnancy and lactation. AB - The hepatic microsomal drug metabolism during pregnancy and lactation was studied. Four days post partum, the concentrations of cytochrome P450 and cytochrome b5 were reduced by 50% when compared with pregnant rats, at day 10 of gestation. Within this time period the N-demethylation of aminopyrine, the rate of aldrin epoxidation and the N-demethylation of demethylnitrosamine was reduced by 53, 74 and 21%, respectively. However, the rates of ethoxyresorufin-O deethylation did not differ amongst both groups and the deethylation of 4 nitroanisole and the 4-hydroxylation of aniline was increased by 71 and 31%, respectively in lactating rats. Furthermore, the activities of UDP glucuronyltransferase and glutathione S-transferase were increased by 21 and 27%, but those of epoxide hydrolase were reduced by 85%. Western immunoblot analysis of microsomal proteins obtained from pregnant and lactating rats shows that only proteins encoded by the genes of CYP2C6 and CYP3A1 are expressed at detectable levels, whereas the expression of CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1 and CYP4A1 was not detectable in pregnant and lactating rats at a protein loading of 3 micrograms total protein per well. In contrast, in northern blot hybridization experiments, detectable amounts of mRNA of the above named isoenzymes were measurable, but at varying intensities. Based on the northern blot hybridization analysis, an approximate 4-fold and 3-fold increase in CYP2A1 mRNA and CYP3A1 mRNA was found, when lactating rats were compared with female controls or pregnant rats, at day 10 of gestation. PMID- 8347135 TI - Modulation by drugs acting on the autonomic nervous system of platelet-activating factor in the stomach of rats. AB - Platelet-activating factor (PAF), an ether linked choline glycerophospholipid, is a potent initiator of diverse physiological and pathological processes. We have reported that gastric endogenous PAF levels were reduced and the contents of each of its molecular species changed during water-immersion stress in rats (Sugatani J et al., FASEB J 3: 65-70, 1989 and Sugatani J et al., Lipids 26: 1347-1353, 1991). In this study, we determined the effects of autonomic drugs on the level of gastric PAF, its molecular heterogeneity and formation of gastric erosions in unstressed rats and those subjected to water-immersion stress. Atropine, an anticholinergic drug, suppressed both the stress-induced changes and development of gastric lesions. 6-Hydroxydopamine-induced sympathectomy induced a small decrease in the gastric PAF levels and the addition of stress further decreased the PAF levels and development of gastric lesions. Carbamylcholine induced a transient decrease in the gastric PAF level of normal rats, which was not associated with gastric erosion formation. In contrast, the endogenous gastroprotective factor dopamine evoked transient dose- and time-dependent increases in the gastric PAF levels. These observations indicate that cholinergic muscarinic-receptor activation in rats led to decreases in gastric PAF levels and a prolonged and marked decrease in its level was associated with the development of gastric lesions, and that dopamine increases gastric PAF levels. Gastric endogenous PAF levels are closely associated with the autonomic nervous system and should be considered further in investigations of gastric function. PMID- 8347136 TI - Inhibition of melanogenesis in human melanoma cells by novel analogues of the partial histamine (H2) agonist nordimaprit. AB - A series of analogues of the weak histamine (H2) agonist S-[2-(N,N dimethylamine)ethyl] isothiourea (nordimaprit) was produced to investigate the possibility that bulky substituents on the tertiary amine of nordimaprit would enhance potency for depigmentation and killing of melanoma cells. Cell survival studies showed that neither an increase in lipophilicity nor an increase in size of these groups produced selective toxicity, with only the N,N-diisobutyl derivative being more effective than the N,N-diisopropyl derivative in killing the constitutively pigmented human melanoma cell line MM418. The most hydrophobic analogue, the N,N-dibenzyl derivative, was also the most toxic to all cell lines tested. The association of toxicity with lipophilicity was confirmed by the piperidine derivative having greater toxicity than the less hydrophobic morpholine analogue. The ability to decrease tyrosinase activity was lost when lipophilicity and size of the N-terminal groups were increased, but these analogues produced marked depigmentation, even greater than that found with either nordimaprit or the diisopropyl derivative. Surprisingly, an increase in tyrosinase activity was achieved, the most potent agent being the N-ethyl-N anilino analogue which caused complete depigmentation (0.6% of control) and elevated tyrosinase activity (148%) in MM418 cells after 1 month of treatment. This indicates that nordimaprit and its derivatives possess two different mechanisms of depigmentation, the first being tyrosinase dependent and the second being tyrosinase independent. The latter pathway is yet to be elucidated but appears to require a high degree of hydrophobicity. PMID- 8347139 TI - Studies on the effect of fenoprofen on the activation and oxidation of long chain and very long chain fatty acids in hepatocytes and subcellular fractions from rat liver. AB - We studied the effect of fenoprofen on the activation of palmitic acid (C16:0), lignoceric acid (C24:0) and cerotic acid (C26:0) in microsomal and peroxisomal fractions from rat liver. Fenoprofen was found to inhibit the formation of palmitoyl-CoA in both microsomal and peroxisomal fractions whereas the formation of lignoceroyl-CoA and cerotoyl-CoA was not inhibited at all. In freshly isolated rat hepatocytes palmitic acid beta-oxidation was progressively inhibited at increasing concentrations of fenoprofen, most probably due to its inhibitory effect on palmitoyl-CoA synthetase activity. On the other hand, fenoprofen was also found to inhibit the beta-oxidation of lignoceric acid and cerotic acid in rat hepatocytes. It is shown that the acyl-CoA oxidase activity with lignoceroyl CoA as substrate was inhibited by fenoprofen whereas the palmitoyl-CoA and pristanoyl-CoA oxidase activities were not inhibited by fenoprofen. This finding provides an explanation for the inhibitory effect of fenoprofen on lignocerate and cerotate beta-oxidation in hepatocytes. PMID- 8347137 TI - Differential role in lipid peroxidation between rat P450 1A1 and P450 1A2. AB - The role of cytochrome P450 (P450) in lipid peroxidation induced by NADPH or peroxide was investigated in a reconstituted system. When cumene hydroperoxide, t butyl hydroperoxide and hydrogen peroxide were used as initiators, the rates of malondialdehyde (MDA) formation were much higher in a reconstituted system containing P450 1A1 than those observed in a reconstituted system containing P450 1A2. In contrast to peroxide-induced lipid peroxidation, P450 1A2 catalysed NADPH induced lipid peroxidation more effectively than did P450 1A1 regardless of the presence of ADP-Fe(NO3)3. Carbon monoxide inhibited NADPH-induced formation of MDA in a reconstituted system containing P450 1A2, but not P450 1A1. In addition, superoxide dismutase (SOD) was an effective inhibitor in a NADPH-induced lipid peroxidation system catalysed by P450 1A2 but not by P450 1A1. These results suggest that a peroxide-induced reaction might proceed readily with P450 1A1, whereas P450 1A2 mainly functions in NADPH-induced lipid peroxidation via generation of an active oxygen species. It is furthermore indicated that the difference in the effect of SOD in NADPH-induced lipid peroxidation depends on the P450 used. PMID- 8347138 TI - Triazolobenzodiazepines: a new class of stimulators of tissue-type plasminogen activator synthesis in human endothelial cells. AB - In our search for compounds that can stimulate endogenous fibrinolysis, we have found that certain triazolobenzodiazepines enhance the production of tissue-type plasminogen activator (t-PA) by vascular endothelial cells maintained in vitro, with no or even a lowering effect on plasminogen activator inhibitor type-1 (PAI 1) production. The most active compounds tested, U-34599, U-46195 and U-51477, were studied in more detail and showed a time- and dose-dependent increase in the production of t-PA by human umbilical vein endothelial cells. At optimal stimulatory concentrations (about 10 microM), the three compounds stimulated t-PA expression about 2-fold after 24 hr and maximally about 4-fold after 48 hr of incubation; this maximal increase in t-PA synthesis was sustained at prolonged incubations of 72 or 96 hr. The triazolobenzodiazepine effects on t-PA production were accompanied by parallel increases in t-PA mRNA levels, without marked changes in PAI-1 or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA concentrations. Numerous analogues of the three lead compounds were then tested to determine the relationship between benzodiazepine structure and the ability to stimulate t-PA production. No positive correlation was found between the ability of the various triazolobenzodiazepines to stimulate t-PA production and their affinity for the benzodiazepine receptor. In agreement with this, no specific binding of [3H]flunitrazepam, a specific ligand for benzodiazepine receptors, to endothelial cell membrane preparations was observed. Thus, it is unlikely that the triazolobenzodiazepines act through central-type benzodiazepine receptors to stimulate t-PA production. Similarly, no evidence was found for the presence of peripheral-type benzodiazepine receptors on endothelial cell membranes. The ability of the benzodiazepines to stimulate t-PA production, however, appeared to be related to their platelet-activating factor (PAF) antagonist activity. Despite this finding, several non-benzodiazepine PAF antagonists did not stimulate t-PA production. While the precise mechanism of action is not yet clear, selected benzodiazepine analogues possessing PAF antagonist activity stimulate the production of t-PA by endothelial cells in vitro. PMID- 8347140 TI - Interaction of fluoroethane chlorofluorocarbon (CFC) substitutes with microsomal cytochrome P450. Stimulation of P450 activity and chlorodifluoroethene metabolism. AB - The abilities of halothane and the fluoroethane chlorofluorocarbon (CFC) substitutes, FC-123, FC-133a, FC-124, FC-134a and FC-125, to stimulate cytochrome P450 activities and 2-chloro-1,1-difluoroethene (CDE) defluorination in hepatic microsomes from phenobarbital-treated rabbits were compared. At 1% (v/v) each, halothane and FC-123 similarly increased the consumption of NADPH and O2 by 300 and 100%, respectively, over that in microsomes without substrate. FC-133a and FC 124 were less effective, increasing NADPH and O2 consumption by 150-200 and 70%. FC-134a and FC-125 were the least effective, increasing NADPH and O2 consumption by only 70 and 50%, respectively. No metabolism of any fluoroethane could be detected under the incubation conditions used. Halothane and FC-123 were most effective in stimulating CDE metabolism with increases of CDE defluorination ranging from 1.5- to 2-fold. FC-133a and FC-124 enhanced CDE oxidation 89 and 74%, respectively, and FC-134a and FC-125 had no effect. While CDE metabolism was enhanced in the presence of the fluoroethanes, no additional NADPH or O2 was consumed when halothane or FC-124 was incubated with CDE compared with incubations containing only halothane or FC-124. Log-log plots of NADPH consumption and CDE metabolism with the olive oil/gas partition coefficients of each fluoroethane showed linear relationships. These data demonstrate that the activity of the fluoroethanes in stimulating P450 activity and CDE metabolism is a function of their lipid solubility, and fluoroethane-enhanced CDE metabolism is related to the ability of these compounds to increase uncoupled P450 activity. PMID- 8347142 TI - Cytotoxic mechanisms of 5-fluoropyrimidines. Relationships with poly(ADP-ribose) polymerase activity, DNA strand breakage and incorporation into nucleic acids. AB - A comparative study of the cytotoxic mechanisms of 5-fluorouracil (FU) and 5 fluoro-2'-deoxyuridine (FdUrd) was carried out in Chinese hamster ovary K1 (CHO K1) cells. The poly(ADP-ribose) polymerase (PADPRP) inhibitor, 3-aminobenzamide (3AB, 3 mM) enhanced the cytotoxicity of FU with a dose enhancement factor at 10% survival of 2. This enhancement was also evident when cells were grown in dThd free medium, but the IC50 for FU was reduced from 50 to 35 microM. In contrast, 3AB did not enhance the cytotoxicity of FdUrd but exerted a small protective effect. The IC50 for FdUrd was reduced from 35 to 1.25 microM in dThd-free medium. A 55% reduction in NAD levels was seen within 6 hr of 5.0 microM FdUrd treatment in dThd-free medium, and this reduction persisted over 24 hr. This drop was prevented by co-incubation with 3AB, indicating that PADPRP activation was the cause of the NAD depletion. In contrast, FU treatment had little or no effect on NAD levels. Alkaline elution analysis of cells treated with up to 150 microM FU revealed no DNA strand breaks in mature DNA, but an increase in breaks in nascent DNA. Co-incubation with 3AB had little or no effect on strand break levels. FdUrd (up to 40 microM) produced a dose-dependent increase in both mature and nascent DNA strand breaks. Analysis using a "relative elution" formula demonstrated that 3AB increased the amount of FdUrd-induced strand breaks (at doses < or = 5-100 microM) in mature DNA. Whereas FU elution profiles for nascent DNA were biphasic, those for FdUrd were linear. Co-incubation with 3AB increased [3H]FU incorporation into both RNA (by 50%) and DNA (45%). 3AB also enhanced [3H]FdUrd incorporation (by 40%) into RNA but had no effect on incorporation into DNA. These data indicate that in addition to acting as an inhibitor of PADPRP, 3AB exerts other metabolic effects. PMID- 8347141 TI - Valproate and mitochondria. PMID- 8347143 TI - The effect of desferrioxamine on iron metabolism and lipid peroxidation in hepatocytes of C57BL/10 mice in experimental uroporphyria. AB - The effects of the iron chelator desferrioxamine (DFx) on liver iron accumulation, malondialdehyde (MDA) production, porphyrin accumulation and uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37) activity were investigated over a period of 14 weeks in C57BL/10 mice, made porphyric by the administration of hexachlorobenzene (HCB) and iron-dextran (Imferon, IMF) or IMF alone. In addition, we measured the amount of low molecular weight (LMW) iron in liver tissue to determine a possible correlation with MDA production. These experiments showed that combined treatment with HCB + IMF, as well as IMF alone, resulted in porphyrin accumulation, increased MDA production and reduced URO-D activity, whereas HCB alone had no effect. DFx caused a reduction in hepatic porphyrins, this reduction being more distinct in the IMF group than in the HCB + IMF group. The effect of DFx on MDA production and URO-D activity was in agreement with the results on porphyrin accumulation. LMW iron pool measurements at 11 weeks correlated well with data on MDA production in all treated groups in that period (r2 = 0.84), suggesting both variables are interdependent. In conclusion, these results suggest an important role for iron in porphyrin accumulation, probably through its catalytic role in the generation of oxygen-related free radicals, resulting in direct damage to URO-D. The effectiveness of DFx in reducing porphyrin accumulation is probably the result of a reduction in LMW iron, thus diminishing the amount of iron available for a catalytic role in the generation of oxygen-related free radicals. PMID- 8347144 TI - Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine. AB - The effects of piperine, a major ingredient of black pepper, on UDP-glucose dehydrogenase (UDP-GDH) and glucuronidation potentials of rat and guinea pig liver and intestine were studied. Piperine caused a concentration-related strong inhibition of UDP-GDH (50% at 10 microM) reversibly and equipotently, in both tissues. Partially purified rat liver UDP-GDH was used to obtain the kinetic values at pH optima of 9.4 and 8.6. At pH 9.4: KmUDP-glucose = 15 microM, Vmax = 5.2 nmol NADH/min/mg protein, Ki = 6 microM. With NAD, a Ki of 16 microM was obtained. At pH 8.6: Km = 35 microM, Vmax = 7.5 nmol, Ki = 15 microM. In all of these cases, piperine caused non-competitive inhibition. Data from structure activity comparisons of piperine analogs indicated that the presence of conjugated double bonds in the side chain of the molecule is a factor in piperine inhibition. However, the UDP-glucuronic acid (UDPGA) contents were decreased less effectively by piperine in isolated rat hepatocytes compared with enterocytes of guinea pig small intestine. Piperine at 50 microM caused a marginal decrease of UDPGA in hepatocytes when the rate of glucuronidation of 3-hydroxybenzo[a]pyrene (3-OH-BP) decreased by about 40%. The decrease obtained at 10 microM piperine in intestinal cells was comparable to that obtained at 50-100 microM in hepatocytes. UDP-glucuronosyltransferase (UGT) activities towards 3-OH-BP (UGT1A1) and 4-OH biphenyl (UGT2B1) were also determined. Piperine did not affect the rate of glucuronidation of 4-OH-biphenyl in rat liver, whereas that of 3-OH-BP was impaired significantly. In guinea pig small intestine, both these activities were inhibited significantly requiring less than 25 microM piperine to produce a more than 50% inhibition of UGT(s). The results suggested that (i) piperine is a potent inhibitor of UDP-GDH, (ii) inhibition is offered exclusively by the conjugated double bonds of the molecule, and (iii) piperine exerts stronger effects on intestinal glucuronidation than in rat liver. PMID- 8347145 TI - Trimethylamine N-oxygenation and N-demethylation in rat liver microsomes. AB - The in vitro oxidation of trimethylamine (TMA) to TMA N-oxide (TMAO) and dimethylamine (DMA) was studied in rat liver microsomes. Pretreatment of rats with phenobarbital, 3-methylcholanthrene, ethanol or pregnenolone 16 alpha carbonitrile had little or no effect on the liver microsomal metabolism of TMA to TMAO or DMA. Changing the atmosphere in the incubation vessel from 20% oxygen/80% nitrogen (air) to 100% oxygen had a selective stimulatory effect on the N oxygenation of TMA but did not affect TMA N-demethylation. In addition, the Km for TMA N-demethylation was 5-fold higher than for the N-oxygenation reaction. The results of these studies suggest that the enzyme systems responsible for N demethylation and N-oxygenation are different and that they are under different regulatory control. Carbon monoxide (CO/O2 = 80/20) had little or no inhibitory effect on either the N-demethylation or N-oxygenation of TMA by liver microsomes from control or pregnenolone 16 alpha-carbonitrile-treated rats. Additional studies indicated that methimazole, an inhibitor of FAD-containing monooxygenase (FMO), was a potent inhibitor of TMA oxidation. Preincubation of liver microsomes from control or pregnenolone 16 alpha-carbonitrile-treated rats at 37 degrees for 10 min without NADP(H) (a procedure that irreversibly inactivated FMO activity) resulted in > 95% inhibition of TMA N-demethylation and N-oxygenation, and this inhibition was prevented by including a NADPH-generating system in the preincubation medium (a procedure for preventing the thermal inactivation of FMO activity). The data suggest that FMOs are the major enzymes responsible for N demethylation and N-oxygenation of TMA in rat liver microsomes. PMID- 8347146 TI - Fish oil preparations rich in docosahexaenoic acid modify platelet responsiveness to prostaglandin-endoperoxide/thromboxane A2 receptor agonists. AB - The effects of daily dietary supplementation for 6 weeks with either 4.5 g eicosapentaenoic acid (EPA) and 3.35 g docosahexaenoic acid (DHA) (group I, EPA/DHA = 1.33) or 3.5 g EPA and 6.4 g DHA (group II, EPA/DHA = 0.54) on platelet responsiveness to the stable prostaglandin (PG)-endoperoxide analogue 9,11 dideoxy,9 alpha-11 alpha-methanoepoxy-PGF2 alpha (U 46619) were studied in healthy volunteers. Dose-response curves (DRC) of U 46619-induced platelet aggregation were analysed by computerized non-linear curve fitting. In group I, the concentration of U 46619 required for half-maximum platelet aggregation (EC50) remained unchanged, whereas the Hill coefficient decreased from 6.2 to 3.3 (P < 0.02). In group II, characterized by a high intake of DHA, a considerable increase of EC50 from 0.3 to 1.4 microM was found (P < 0.02). These results suggest different effects of EPA and DHA on the platelet thromboxane/endoperoxide amplifying system. The considerable shift of the DRC in group II suggests a direct effect of DHA on the presentation of the endoperoxide receptor and/or post receptoral events. PMID- 8347148 TI - Fasting-induced depletion of glutathione in the aging mouse. AB - Previous results indicate that aging is associated with a general deficiency of glutathione (GSH). As fasting is also known to lower hepatic GSH levels, we investigated the combined effects of aging and 24 hr of food deprivation on liver, kidney and blood GSH and cyst(e)ine levels in C57BL/6N mice of ages 6 (young), 12 (mature) and 24 (old) months. No age-related differences in baseline hepatic GSH were observed in these mice, consistent with previous findings where the deficiency in liver is not apparent until about 29 months of age. By 6 hr of fasting, an age-related reduction in hepatic GSH was evident, culminating in a 4 fold greater decrease during maturation, and a 5-fold greater decrease during aging (P < 0.001) compared to young animals. Liver weight also declined, decreasing total liver GSH content by 24% in young, 44% in mature, and 56% in old mice. Renal GSH and hepatic cyst(e)ine concentrations were unaffected by fasting. In young and mature mice, depletion of hepatic GSH was accompanied by a concomitant increase in blood GSH and kidney cyst(e)ine levels after 6 hr of fasting, suggesting enhancement of hepatic GSH efflux. However, in old animals, GSH depletion was associated with decreased blood GSH and kidney cyst(e)ine. Altogether, these results suggest that the stress of fasting reveals aging changes in hepatic GSH homeostasis occurring well before the GSH deficiency of aging is observed. These aging changes are likely due to decreased GSH turnover resulting from impaired biosynthesis. PMID- 8347147 TI - Anti-HIV-1 activity and cellular pharmacology of various analogs of gossypol. AB - We previously reported that the racemic mixture and both enantiomers of gossypol inhibit the replication of human immunodeficiency virus-type 1 (HIV-1) (Lin et al., Antimicrob Agents Chemother 33: 2149-2151, 1989). The present study evaluates the activities of a variety of analogs of gossypol as well as a few non gossypol analogs. Compounds 2, 3, 10, and 13 were slightly more inhibitory than ( )-gossypol to the replication of HIV-1 in cell culture. Compounds 4 and 8 were cytotoxic to human peripheral blood monocyte (PBM) cells, and compounds 2 and 3 were cytotoxic to Vero cells but not PBM cells. The effects of the two enantiomers of gossypol on the cell volume and migration of H9 cells through the cell cycle were evaluated during 72 hr of incubation. The (-)-enantiomer of gossypol was more toxic to H9 cells than the (+)-enantiomer of gossypol as evidenced by cell destruction. Prior to cell destruction, there appeared to be no significant effect on cell cycle distribution with either enantiomer. PMID- 8347149 TI - Permeation and metabolism of anti-HIV and endogenous nucleosides in human immune effector cells. AB - Numerous anti-HIV drugs are synthetic analogs of endogenous nucleosides. Therefore it is of interest to see if a facilitated nucleoside transport system exists to mediate their uptake into human immune effector cells that are known HIV targets. Nucleoside permeation and metabolism in lymphocytes, macrophages and bone marrow cells isolated from healthy human volunteers were studied, using uridine as the prototype endogenous nucleoside. There are saturable broad specificity nucleoside transport systems in all three cell types, all of which were inhibited by dipyridamole. The Vmax and Km values for uridine transport were 0.05 +/- 0.01 pmol/sec/10(6) cells and 18.4 +/- 4.2 microM, respectively, for lymphocytes, 0.04 +/- 0.01 pmol/sec/10(6) cells and 25.3 +/- 6.6 microM, respectively, for macrophages, and 0.03 +/- 0.01 pmol/sec/10(6) cells and 90.2 +/ 10.1 microM, respectively, for bone marrow mononuclear cells. Anti-HIV dideoxynucleosides such as azidothymidine (AZT), 2',3'-dideoxycytidine (DDC), 2',3'-dideoxyinosine (DDI), 2',3'-dideoxyadenosine (DDA), and 2',3' dideoxythymidine (DDT) are not substrates of this nucleotide transport system; hence, little or no drug accumulated inside the cells after 60 sec. Equilibration of cells with uridine or dideoxynucleosides for 2 hr resulted in high levels of cellular uridine and DDA, low levels of cellular AZT, but undetectable levels of the other analogs in all three cell types. Active metabolite levels in lymphocytes as assayed by HPLC correlated with the drug permeation results. Our data demonstrated that DDC, DDI, and DDT are not substrates for the nucleoside transporter and cannot diffuse readily across the cell membrane of human immune effector cells. Future anti-HIV drug development efforts should consider drugs that are substrates of the nucleotide transporter to ensure rapid and complete uptake into target cells. PMID- 8347150 TI - Effect of O6-benzylguanine on the sensitivity of human colon tumor xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). AB - A number of trials were conducted to determine the effect of O6-benzylguanine pretreatment on the sensitivity of human colon tumor xenografts to the antitumor effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). O6-Benzylguanine has been shown to inactivate the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), which is primarily responsible for resistance to alkylnitrosoureas including BCNU. Colon tumor xenografts carried in nude mice were analyzed for their AGT content, and tumors with low, intermediate and high levels were chosen for further study. The AGT activity of HC-1, GC-3, VRC-5 and CX-1 human colon tumor xenografts was 16, 113, 180 and 367 fmol/mg protein, respectively. Treatment of mice consisted of vehicle alone, 6.25 to 50 mg/kg BCNU administered alone or BCNU (6.25 to 25 mg/kg) 1 hr after 120 mg/kg O6-benzylguanine on days 7 and 14 post-inoculation. Toxicity studies revealed that pretreatment with O6 benzylguanine increased the toxicity of BCNU, requiring administration of about 4 fold less drug. The growth of the VRC-5 tumor at day 42 post-inoculation was inhibited by 39% following treatment with 12.5 mg/kg BCNU alone and 92% when BCNU was combined with O6-benzylguanine pretreatment. The combination of O6 benzylguanine and BCNU (12.5 mg/kg) at day 42 resulted in an inhibition of HC-1 and CX-1 tumor growth by 84 and 72%, whereas BCNU alone inhibited growth by 54 and 14%, respectively. Therefore, the degree to which the antitumor effect of BCNU was increased by O6-benzylguanine pretreatment was dependent on the AGT activity, with a greater effect in tumors of intermediate or high activity. These data suggest that there is a role for O6-benzylguanine combined with BCNU in the treatment of human colon tumors. PMID- 8347151 TI - Muscarinic receptors in isolated guinea pig pancreatic ducts. AB - Biochemical and pharmacological characteristics of muscarinic cholinergic receptors in isolated guinea pig pancreatic ducts were determined in the present study. Duct homogenates bound 6.82 +/- 0.69 fmol of [3H]N-methylscopolamine ([3H]NMS)/micrograms of DNA with a Kd of 0.73 +/- 0.05 nM. The density of [3H]NMS binding sites in the excretory ducts was seven times greater than that in acini from the same pancreases. Competition binding studies with atropine, pirenzepine, 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3 b] [1,4]benzodiazepine-6-one (AF-DX 116), and 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP) indicated that both M2 and M3 subtypes of muscarinic receptors are present in these preparations of isolated pancreatic ducts. Electrophoretic analysis of [3H]propylbenzilylcholine mustard-labeled unreduced and reduced duct muscarinic receptors provided molecular mass estimates of 62.6 +/- 2.5 and 58.0 +/- 1.6 kDa, respectively. Deglycosylation of ductal muscarinic receptors with N-glycanase decreased their apparent molecular mass by approximately 4 kDa. These results demonstrate that isolated pancreatic ducts express both M2 and M3 muscarinic receptors, with the former subtype predominating. PMID- 8347152 TI - Effects of NB-598, a potent squalene epoxidase inhibitor, on the apical membrane uptake of cholesterol and basolateral membrane secretion of lipids in Caco-2 cells. AB - Caco-2 cells grown on membrane filters were used as a model to study the effects of NB-598, an inhibitor of squalene epoxidase, on cholesterol absorption from the intestinal epithelia. NB-598 (10 microM) inhibited the synthesis of sterol and sterol ester from [14C]acetate without affecting the synthesis of other lipids such as phospholipids (PL), free fatty acids (FFA) and triacylglycerol (TG). When labeled lipid was apically loaded as a micellar lipid solution into Caco-2 cell cultures, NB-598 reduced basolaterally secreted radioactivity in cholesterol, cholesterol ester, PL and TG. Furthermore, NB-598 suppressed the basolateral secretion of apolipoprotein (apo) B. When microsomes prepared from control Caco-2 cells were incubated with 10 microM NB-598, acyl CoA:cholesterol acyltransferase (ACAT) activity was inhibited slightly. After incubating Caco-2 cells with 10 microM NB-598, a slight reduction in cellular ACAT activity was also observed. These results suggest that suppression of the secretion of particles containing apo B and reduction of cellular ACAT activity in the intestinal epithelia are part of the mechanism of the cholesterol-lowering effect of NB-598. PMID- 8347153 TI - Modulatory effect of hyperthermia on hepatic microsomal cytochrome P450 in mice. AB - It is widely known that the clearance of drugs is often compromised during episodes of infectious disease via a down-regulation of cytochrome P450 (P450) at a pre-translational step in enzyme synthesis. Etiocholanolone (ETC), a potent inflammatory agent, induces fever in humans and causes a decrease in the clearance of certain drugs that are metabolized by P450. On this basis it is widely believed that the fever per se rather than the immune modulation that occurs during infections may have a major role in depression of microsomal P450 enzymes during viral infections in humans. In the present study, we demonstrated that although ETC did not induce hyperthermia in mice, it still evoked a depression of the levels of P450 in hepatic microsomes. Ethoxyresorufin O deethylase (EROD) was also inhibited significantly when hepatic microsomes were incubated with various concentrations of ETC in vitro. P450 levels and EROD activities remained unchanged following hyperthermia that was induced by a non inflammatory procedure using 2,4-dinitrophenol. Provided the response in rodents is similar to humans, these results indicate that the depression of drug biotransformation by ETC in humans is more likely to be caused by the direct effects of this agent or other mechanisms rather than by the fever it produces. This may suggest that the loss of drug metabolism in humans during infections is due to the activation of host defence responses rather than to the febrile nature of the illness. PMID- 8347154 TI - Inhibition of rabbit aortic angiotensin II (AII) receptor by CV-11974, a new nonpeptide AII antagonist. AB - The angiotensin II (AII) antagonistic action of CV-11974 (2-ethoxy-1-[[2'-(1H tetrazol-5-yl)biphenyl-4-yl]methyl] benzimidazole-7-carboxylic acid) was investigated in an AII-receptor binding assay using rabbit aortic membranes and an AII-induced contraction assay using rabbit aortic strips. A single class of [125I]AII-(Sar1,Ile8) binding sites was found in the membranes with a dissociation constant (Kd) of 0.15 nM and a receptor concentration (Bmax) of 86.9 fmol/mg protein. CV-11974 markedly reduced Kd without affecting Bmax. The specific binding of [125I]AII-(Sar1,Ile8) in this preparation was inhibited completely by CV-11974 [the inhibition constant (Ki) = 0.64 nM], DuP 753 [an angiotensin II type I (AT1) receptor-selective antagonist] (Ki = 51 nM) and EXP3174 (an active metabolite of DuP 753) (Ki = 6.8 nM), but was not affected by PD123177 (an AT2 receptor-selective antagonist). These results suggest that the single binding site in rabbit aortic membranes is an AT1 receptor subtype. The affinity of CV-11974 to these AT1 receptors was approximately 80 and 10 times higher than that of DuP 753 and EXP3174, respectively. CV-11974 showed no appreciable affinity for the AT2 receptors found in bovine cerebellum. In the in vitro functional study, CV-11974 markedly reduced the AII-induced maximal contractile response of rabbit aortic strips (pD'2 = 9.97). In contrast, Compound 7-H, which lacks the carboxyl group at the benzimidazole ring of CV-11974, inhibited the contraction in a competitive manner. The inhibition by CV-11974 was long lasting. These results suggest that CV-11974 is a potent and long-acting AT1 receptor-selective, competitive antagonist. The carboxyl group at the benzimidazole ring plays an important role in the interaction between CV-11974 and the AT1 receptor. PMID- 8347155 TI - 13-cis-retinoic acid and hepatic steatosis in rats. AB - The effect of administration of 13-cis-retinoic acid (100 mg/kg diet) on lipid metabolism was examined in male rats fed either a 20% casein + 0.3% methionine diet, a 20% casein diet, a 10% casein + 0.3% methionine diet, or a 10% casein + 0.6% methionine diet for 10 days. Hepatic triglyceride concentrations of rats fed either 10% casein diet were 3-fold greater than animals receiving diets containing 20% casein. The addition of 13-cis-retinoic acid to the diet further increased the total hepatic lipid (43-56%) and triglyceride (approximately 2 fold) concentrations in rats fed the 10% casein diets. 13-cis-Retinoic acid supplementation did not alter the total liver lipid or triglyceride concentrations in rats fed either of the 20% casein diets. Thus, under specific dietary conditions, the administration of 13-cis-retinoic acid resulted in a marked accumulation of hepatic lipids which did not appear to be related to the total methionine content of the diet nor to the hepatic concentrations of S adenosylmethionine and glutathione. In addition, all four groups of 13-cis retinoic acid-fed rats exhibited elevations in the concentration of serum triglycerides, and 10-20% reductions in serum cholesterol concentrations. PMID- 8347156 TI - Polyclonal amanitin-specific antibodies: production and cytoprotective properties in vitro. AB - The amanitins found in several mushroom species are responsible for many deaths every year. Based on its successful application to cardiac glycoside overdose, immunotherapy could be applicable to amanitin toxicity. Therefore, we produced polyclonal amanitin antibodies by immunizing rabbits with a novel conjugate of alpha-amanitin. Purified antibodies had an average association constant for alpha amanitin of 1.3 x 10(9) M-1. A partially protective effect of the antibodies against amanitin toxicity in vitro in Chang cells was evident at a molar ratio of antibody binding sites to alpha-amanitin of 4:1. Together with reported studies in vivo, these investigations indicate the potential of immunotherapy for amanitin poisoning. PMID- 8347157 TI - Non-ionophoretic elevation of intracellular Ca2+ by Lonidamine. AB - Lonidamine is an antispermatogenic and anticancer drug that is believed to act by inhibition of energy metabolism. In this study, the effects of Lonidamine on the concentration of intracellular free Ca2+ of several tumor cell lines were assessed because of the important role that cytosolic Ca2+ plays in cell viability and proliferation. The presence of 300 microM Lonidamine resulted in large elevations of cytosolic Ca2+ (> 100 nM) in AS-30D rat ascites hepatoma cells and in cultured EMT6 murine mammary adenocarcinoma cells but had little effect on cultured NCI-H345 human small cell lung cancer cells. The apparent EC50 for Lonidamine was approximately 175 microM. The source of elevated cytosolic Ca2+ was primarily intracellular stores, and the effects of Lonidamine on Ca2+ efflux from these stores did not appear to be due to an ionophoretic action of this compound or to a decline in the level of cellular ATP. These results indicate that the Ca2+ homeostasis of certain lines of tumor cells is specifically altered by Lonidamine at concentrations known to affect cell proliferation. PMID- 8347158 TI - Maintenance of xenobiotic metabolism and toxicity in rat hepatocyte cultures after cell preservation at 4 degrees. AB - Isolated rat hepatocytes were stored at 4 degrees in modified University of Wisconsin solution for 22-24 hr and then placed into culture. Satisfactory viabilities were obtained for all preparations. No loss of alcohol dehydrogenase or 7-ethoxy-3,4-dimethylcoumarin O-deethylase activity was observed in the cold stored relative to the control cultures. The protein and glutathione contents, allyl alcohol and precocene II (PII) toxicities were also similar, as was the PII mediated glutathione depletion. For the parameters measured, cultures of cold stored hepatocytes were identical to normal cultures. PMID- 8347159 TI - Alkylation of human albumin by the antimalarial artemisinin. AB - The interaction between artemisinin and human serum was studied in vitro using [3H]dihydroartemisinin and [14C]artemisinin. Approximately 20% of added drug was covalently bound to albumin in 24 hr. The results of electrospray ionization mass spectra showed that albumin had an M(r) value of 66,745 +/- 35 and the drug-bound albumin had an M(r) of 67,223 +/- 34. The binding was blocked 15 and 58% by iodoacetamide (IA) and N-ethylmaleimide, respectively, and 80% by the combination of IA and succinic anhydride. Hemin and Fe2+ increased the binding by 40 and 10%, respectively, whereas deferoxamine inhibited the binding by 10%. Therefore, we conclude that the binding between artemisinin and albumin probably involves thiol and amino groups via both iron-dependent and -independent reactions. PMID- 8347160 TI - Effect of anthracyclines on phospholipase A2 activity and prostaglandin E2 production in rat gastric mucosa. AB - The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were investigated by analysis of the composition of fatty acids. Enzymatic activities involved in the turnover of membrane phospholipids such as lysophospholipase (LPase, EC 3.1.1.5) and acyl-CoA lysophosphatidylcholine: acyltransferase (ACLAT, EC 2.3.1.23), and in the detoxification of lipid hydroperoxides, selenium-dependent glutathione-peroxidase (GSH-PX, EC 1.11.1.9) were measured after injection of the drugs for 4 consecutive days. Pirarubicin does not give rise to any changes in these activities but doxorubicin and epirubicin decreased PGE2 production and the activities of PLA2, LPase and ACLAT. GSH-PX activity was not changed by any of the drugs. The decrease in PLA2 activity does not seem to be related to variations in membrane lipid composition because the total phospholipids content was unchanged. The P/S (polyunsaturated/saturated) ratio increased in the doxorubicin group and decreased in the epirubicin group, and the unsaturation index was moderately modified. Arachidonic acid was increased only in the doxorubicin group. In vitro, PLA2 activity was not inhibited by the three drugs in the micromolar range. A marked inhibition was observed at 2.5 mM for pirarubicin and at 1.0 mM for doxorubicin and epirubicin. The Lineweaver-Burk representation showed that these inhibitions were of an uncompetitive type. Pirarubicin may therefore be considered to be an anthracycline without marked side-effects on gastric mucosa. However, the in vitro inhibition of PLA2 activity by anthracyclines does not fully explain the in vitro decrease in PLA2 specific activity observed after doxorubicin and epirubicin treatment, and in this context membrane structure modifications unconnected with the lipid composition can not be excluded. In vivo these phenomena may affect PGE2 synthesis, whose level was lower in the doxorubicin and epirubicin groups than in control group. PMID- 8347161 TI - Studies on the in vitro reactivity of clofibryl and fenofibryl glucuronides. Evidence for protein binding via a Schiff's base mechanism. AB - Clofibryl and fenofibryl acyl (ester) glucuronides (CAG and FAG) are major metabolites in humans of the hypolipidaemic drugs clofibrate and fenofibrate, respectively. We have investigated three inter-related aspects of the reactivity of CAG and FAG in human serum albumin (HSA) solution, human plasma and in buffer at pH 7.0: namely (a) rearrangement via acyl migration to glucuronic acid esters of clofibric acid (CA) and fenofibric acid (FA), (b) hydrolysis of the parent glucuronide and rearrangement products to yield CA and FA and (c) the formation of covalent adducts with albumin and plasma protein. CAG was more reactive than FAG in all media, especially the protein solutions. The reactivity of both glucuronides was accelerated in protein solution compared with buffer and this was more marked in plasma than in HSA solution. The predominant reaction during the initial stages of the incubation was formation of isomeric rearrangement products. In the protein solutions, CA and FA were the major reaction products after 24 hr, compared to the rearranged isomers in buffer. Protein binding of 14C to HSA was markedly higher after incubation of CAG and FAG labelled on the glucuronyl moiety compared with the label on the aglycone. This is consistent with the covalent binding of CAG and FAG to protein proceeding via the formation of a Schiff's base rather than by transacylation. PMID- 8347162 TI - The susceptibility of the malarial parasite Plasmodium falciparum to quinoline containing drugs is correlated to the lipid composition of the infected erythrocyte membranes. AB - The anti-malarial action of quinoline-containing compounds depends on various membrane-related processes, and drug resistance could depend, among other factors, on the membrane lipid composition. To verify this hypothesis, the constitution of phospholipid classes and the content of cholesterol of various strains of Plasmodium falciparum-infected human erythrocytes grown in in vitro cultures have been assessed in conjunction with drug susceptibility. It was found that uninfected erythrocytes in the culture serve as a major source for the increased lipid content of malaria-infected cells. Alterations of the phospholipid composition of infected cells that result from parasite lipid metabolism are also reflected in the constitution of uninfected red cells, implying lipid exchange between infected and uninfected cells. An inverse relationship between the content of acidic phospholipids and cholesterol has been observed. Some strains resistant to chloroquine and quinine were sensitive to mefloquine, and vice versa. Resistance to chloroquine or quinine was found to be directly related to the content of acidic phospholipids, while that of mafloquine displayed an inverse correlation. Concomitantly, the resistance to chloroquine was inversely related to the content of cholesterol, while the sensitivity to mefloquine decreased with cholesterol concentration. The possible mechanisms that could account for these observations are briefly discussed. PMID- 8347163 TI - Simultaneous measurements of glutathione and activated sulphate (PAPS) synthesis rates and the effects of selective inhibition of glutathione conjugation or sulphation of acetaminophen. AB - The aim of the present study was to examine the effects of the hepatotoxic drug acetaminophen (AA) on the synthesis rates of glutathione (GSH), activated sulphate (PAPS; adenosine 3'-phosphate 5'-phosphosulphate) and the AA metabolites AA-GSH and AA-sulphate after selective inhibition of GSH biosynthesis or sulphation in isolated rat hepatocytes. Selective inhibition of the two interdependent metabolic pathways was accomplished by buthionine sulphoximine (BSO) and 2,6-dichloro-4-nitrophenol (DCNP). The synthesis rates of GSH and PAPS were determined simultaneously by a previously described method based on trapping of radioactivity (35S) in the pre-labelled GSH and PAPS pools. Pre-incubation with 10 mM BSO for 30 min depleted GSH by 38% (P < 0.05) and PAPS by 27% (P < 0.05). The depletion resulted in increased PAPS synthesis at low, non-toxic [5-19 nmol/(10(6) cells.min)] (P < 0.05) and at high, toxic [7-30 nmol/10(6) cells.min)] (P < 0.05) AA concentrations. In both cases sulphur is diverted from GSH biosynthesis to sulphoxidation and PAPS synthesis, thereby maintaining the PAPS pool and preserving the sulphation capacity. This corresponds to the finding that AA sulphation was unaffected by BSO irrespective of AA concentration [6 vs 5 and 20 vs 17 nmol/(10(6) cells.hr), respectively]. Even though the GSH synthesis was halved after BSO pre-incubation, the GSH conjugating capacity of AA was well preserved. Incubation with 200 microM DCNP and 5 mM AA diminished PAPS synthesis from 24 to 10 nmol/(10(6) cells.min) (P < 0.02) and reduced AA-sulphate synthesis by 67% compared to experiments without DCNP incubation [4.8 vs 14.7 nmol/(10(6) cells.hr)] (P < 0.05). GSH and AA-GSH synthesis rates did not change compared to control experiments in which sulphation was not inhibited [1165 vs 1487 nmol/(10(6) cells.min), respectively] and [1.7 vs 1.7 nmol/(10(6) cells.hr), respectively]. This indicates that increased sulphur availability due to decreased PAPS synthesis is unable to raise the cysteine pool and stimulate the gamma-glutamyl cycle and GSH synthesis. PMID- 8347164 TI - Monoclonal antibody-directed assessment of toluene induction of rat hepatic cytochrome P450 isozymes. AB - Cytochrome P450 isozymes induced in rat liver by a range of concentrations of toluene were studied with monoclonal antibodies (MAbs) to specific P450 isozymes and by enzyme assays. Nitrosodimethylamine demethylase activity was significantly increased in microsomes from rats exposed to more than 1000 ppm of toluene, an increase that was dose-dependent. Anti-CYP2E1 significantly inhibited the metabolism of toluene to benzyl alcohol (BA) by about 50%, in microsomes from 1000 to 4000 ppm toluene-exposed rats, at low substrate concentration (0.2 mM). With anti-CYP2B1/2, the rate of BA formation was decreased by 15-17% in microsomes from rats of 2000 and 4000 ppm toluene exposures at high substrate concentration (5.0 mM). On the other hand, anti-CYP2C11/6 inhibited the rate of formation of BA in all of the microsomes, but the extent of inhibition was progressively decreased from 55% in control to 33% in 4000 ppm exposure. Immunoblot analysis with anti-CYP2E1 and anti-CYP2B1/2 revealed stronger immunoreactive bands in microsomes from rats exposed to more than 1000 and 2000 ppm of toluene, respectively. Stronger bands were also observed in microsomes from rats of 2000-4000 ppm toluene exposures with anti-CYP3A1/2, but no immunoreactivity appeared with anti-CYP1A1/2. These results suggest that toluene induces CYP2E1, CYP2B1/2 and CYP3A1/2, but reduces CYP2C11/6, and has no effect on CYP1A1/2. PMID- 8347166 TI - The relative effects of phylloquinone and menaquinone-4 on the blood coagulation factor synthesis in vitamin K-deficient rats. AB - Rats were made vitamin K-deficient by feeding them a 1:1 (w/w) mixture of a commercial vitamin K-depleted diet and boiled white rice. After one week of treatment the rats had developed severe vitamin K deficiency, resulting in Thrombotest values of 5-10% of the initial values. In this experimental system the efficacy of phylloquinone (K1) was compared with that of menaquinone-4 (MK-4) by measuring the extent to which the Thrombotest was normalized after the administration of varying doses of the respective vitamins. Oral administration of the vitamins showed that the efficacy of K1 was at least two-fold higher than that of MK-4. As comparable results were obtained after subcutaneous administration of the vitamins, we conclude that after oral administration the intestinal absorption had been quick and nearly complete. A less pronounced effect of K1 and MK-4 was found after colorectal administration. For both forms of vitamin K relatively high amounts (well above the physiological concentration) were required before significant effects on the Thrombotest could be observed. Therefore these data demonstrate the importance of sufficient dietary vitamin K consumption in rats. The efficacy of other menaquinones may be investigated in the same experimental animal model system. PMID- 8347165 TI - Evaluation of human blood lymphocytes as a model to study the effects of drugs on human mitochondria. Effects of low concentrations of amiodarone on fatty acid oxidation, ATP levels and cell survival. AB - Human lymphocytes were assessed as a cellular model for determining the effects of drugs on human mitochondria. Formation of total oxidized 14C-products was maximal with 1 mM [U-14C]palmitic acid, was linear for 90 min, linear with the number of lymphocytes, and decreased by 95% and 77% in the presence of 30 microM rotenone and 2 mM KCN. Seven drugs were tested which had previously been shown to inhibit beta-oxidation in animals; all decreased formation of total oxidized 14C products by human lymphocytes, but with different IC50 values: 35 microM with amiodarone, 2.75 mM with tetracycline and amineptine, 3.75 mM with tianeptine, and more than 10 mM for valproic acid and the ibuprofen enantiomers. Formation of [14C]CO2 either increased or decreased, in relation to the various effects of these drugs on coupling, beta-oxidation, and the tricarboxylic acid cycle. There was a general trend for some relationship between inhibition of fatty acid oxidation and loss of cellular ATP. Those compounds, however, which uncoupled oxidative phosphorylation (2,4-dinitrophenol, amiodarone, ibuprofen) and/or inhibited the mitochondrial respiratory chain (amiodarone, rotenone, KCN) resulted in comparatively higher ATP depletion. Amiodarone, a drug which produces several effects (uncoupling, inhibition of beta-oxidation, of the tricarboxylic acid cycle and of the respiratory chain), caused a dramatic decrease in cellular ATP and cell viability at low concentrations (20-100 microM). Both these effects were prevented by the addition of 5 mM glucose, a substrate for anaerobic glycolysis. We conclude that human lymphocytes may be a useful model for assessing the effects of drugs on human mitochondrial function. IC50 values determined with this model may not necessarily apply, however, to other cells. PMID- 8347167 TI - Integrated system for the screening of the specificity of protein kinase inhibitors. AB - Tyrosine protein kinases (TPKs) play a major role in the transformation of cells. They are currently used as molecular targets for new generations of anticancer compounds. Numerous TPKs have been described from various tissues using either classical molecular biochemical techniques or cloning strategies. As a natural extension of these discoveries, a large number of "specific" inhibitors have been described in the literature. The major problem with these inhibitors is that there is no simple way to compare their specificity and/or selectivity from one report to another. We have set up a simple, straightforward technique to compare the inhibitory potency of 14 classical inhibitors towards six well-described and at least partially purified protein kinases. This technique is based on a new assay, easy to carry out and non-restrictive in terms of the type of protein substrate used. It permits direct comparisons between the results obtained from various sources. Data obtained showed that, when assessed in this integrated system, specificity and selectivity of many "classical" inhibitors are often weak, thus demonstrating that a universal technique such as ours is essential for the molecular screening of new protein kinase inhibitors. Compounds showing specificity for this panel of protein kinases will be more easily targeted to some defined types of oncogene and of transformed cells. PMID- 8347168 TI - The effects of imipramine on the methylation of phosphatidylethanolamine (PE) in the cortical membranes of Wistar rats. AB - This study investigates the effect of imipramine (IMI) on the methylation of phosphatidylethanolamine (PE) in crude cortical membranes of rat brain in vitro and ex vivo. It was found that IMI enhanced the formation of phosphatidyl-N monomethylethanolamine (PME) and phosphatidyl-N,N-dimethylethanolamine (PDE) and inhibited the formation of phosphatidylcholine (PC) in the cortical membranes of rats in vitro. The same effect i.e. increased incorporation of methyl groups in PE and PME and decreased formation of PC was found in the cortical membrane of rats killed 1 hr after intraperitoneal administration of IMI at a single dose of 10 mg/kg. Chronic treatment of rats with IMI for 14 days with a daily dose of 10 mg/kg i.p. led to further inhibition of PC formation but did not affect the formation of PME and PDE and abolished the stimulating effect of IMI on the formation of PME and PDE in vitro. PMID- 8347169 TI - The role of c-Jun protein in thrombin-stimulated expression of preproendothelin-1 mRNA in porcine aortic endothelial cells. AB - Treatment of porcine aortic endothelial cells with thrombin induced a time- and dose-dependent expression of preproendothelin-1 (PPET-1) mRNA. The thrombin induced expression of PPET-1 mRNA was markedly inhibited by calphostin C, a specific inhibitor of protein kinase C, and phorbol 12-myristate 13-acetate (TPA) induced the expression of PPET-1 mRNA dose-dependently, but 4 alpha-phorbol 12, 13-didecanoate, an inactive enantiomer of phorbol ester, had no effect on the expression of PPET-1 mRNA. On the other hand, challenge of the endothelial cells with thrombin induced a marked and time-dependent increase in the binding activity of nuclear extract to the TPA-responsive element. Furthermore, thrombin elicits synthesis of c-Jun protein as well as triggering its dephosphorylation. From these results, it is concluded that thrombin-stimulated expression of PPET-1 mRNA in porcine aortic endothelial cells can be induced not only by c-Jun protein synthesis but also by initial dephosphorylation in response to activation of protein kinase C. PMID- 8347170 TI - Inhibition of rat liver hydroxysteroid sulfotransferase activity by alkylamines. AB - Triethylamine, which was used as an elution solvent for column chromatography to purify chemically synthesized 3'-phosphoadenosine 5'-phosphosulfate (PAPS), was a potent inhibitor of rat liver sulfotransferase (ST) activities toward androsterone and dehydroepiandrosterone, but not ST activities toward cortisol and 2-naphthol. Examination of fourteen primary, secondary and tertiary amines revealed that a secondary amine, di-n-butylamine, and three tertiary amines, triethylamine, tri-n-propylamine and tri-n-butylamine, specifically inhibited ST activities toward androgen. PMID- 8347171 TI - Resistance to DL-alpha-difluoromethylornithine by clinical isolates of Trypanosoma brucei rhodesiense. Role of S-adenosylmethionine. AB - The ornithine decarboxylase (ODC) inhibitor DL-alpha-difluoromethylornithine (DFMO) has emerged as a new treatment for West African sleeping sickness but is less effective against East African sleeping sickness. We examined uncloned clinical isolates of Trypanosoma brucei rhodesiense, agent of the disease in East Africa, which were refractory to DFMO in laboratory infections, for characteristics that would explain their resistance. None of the isolates were from patients treated with DFMO. Two isolates took up [3H]DFMO at 50-70% lower rates than drug-sensitive strains but ODC activities, Ki values for DFMO, spermidine and spermine uptake rates, polyamine content and inhibition of polyamine metabolism by DFMO were statistically (P < 0.05) similar between sensitive and refractory isolates. One cloned strain, continuously passaged in vivo under DFMO pressure and included for comparison, had > 85% lower ODC activity and up to 14-fold higher putrescine uptake rates than sensitive controls. A statistically important trend was the metabolism of S adenosylmethionine (AdoMet): activities of AdoMet synthetase and AdoMet decarboxylase were 2- to 5-fold and 3- to 40-fold lower in resistant strains, respectively, while intracellular AdoMet pools (AdoMet + decarboxylated AdoMet) that were > 60-fold elevated in sensitive strains during DFMO treatment, increased only 9-fold in refractory isolates. The extreme elevation of the AdoMet pool in sensitive isolates from 0.7 to 44 nmol/mg protein and an intracellular pool concentration of approximately 5 mM may lead to an imbalance in methylation of proteins or other cell constituents as a consequence of DFMO action. These studies indicate that the metabolism of AdoMet is altered significantly in DFMO refractory isolates and suggest that differences in AdoMet metabolism may be responsible for increased tolerance to DFMO. PMID- 8347172 TI - Differing effects of the inhibition of poly(ADP-ribose) polymerase on the course of oxidative cell injury in hepatocytes and fibroblasts. AB - The effects of the two inhibitors of poly(ADP-ribose) polymerase, 3 aminobenzamide (ABA) and benzamide (BA), on the oxidative killing of L929 mouse fibroblasts and primary cultures of rat hepatocytes were studied. The killing of L929 cells by tert-butyl hydroperoxide (TBHP) occurred by two mechanisms, one sensitive and the other insensitive to the antioxidant N,N'-diphenylphenylene diamine (DPPD). Cell killing by either mechanism was prevented by the ferric iron chelator deferoxamine. ABA and BA prevented the killing of L929 cells that occurred in the presence, but not in the absence, of DPPD. ABA and BA inhibited the activity of poly(ADP-ribose) polymerase by 85%. Protection was accompanied by the sparing of the depletion of both NAD and ATP, but there was no effect of either ABA or BA on the iron-dependent appearance of single-strand breaks in DNA. Depletion of ATP by treating the fibroblasts with 2-deoxyglucose and sodium azide did not result in any loss of viability. H2O2 similarly killed the L929 cells by a mechanism that depended on a source of ferric iron. However, DPPD had no effect on the cell killing, and ABA and BA completely protected the cells in the presence or absence of DPPD. H2O2 caused the appearance of single-strand breaks that were prevented by deferoxamine, but again not by ABA or BA. ABA and deferoxamine reduced, but did not prevent, the depletion of both NAD and ATP occurring with H2O2. With the cultured hepatocytes, ABA and BA inhibited poly(ADP ribose) polymerase at concentrations that were without effect on either the extent of cell killing or the depletion of NAD occurring with either TBHP, H2O2, or menadione. These data indicate that the relationship between oxidative DNA damage and the genesis of lethal injury is very different in the two types of cells. In the fibroblasts, the appearance of single strand breaks in DNA was accompanied by depletion of NAD and ATP and subsequently by the death of the cells. These events were mediated by the activity of poly(ADP-ribose) polymerase, as inhibition of the enzyme prevented their development. In the hepatocytes, inhibition of poly(ADP-ribose) polymerase was without effect on the oxidative death of the cells. PMID- 8347173 TI - Interaction of caffeine with acetaminophen. 1. Correlation of the effect of caffeine on acetaminophen hepatotoxicity and acetaminophen bioactivation following treatment of mice with various cytochrome P450 inducing agents. AB - The combination of caffeine with acetaminophen (APAP) is used widely in the treatment of headache. The effects of caffeine on APAP-induced hepatotoxicity and APAP bioactivation by liver microsomes from uninduced mice and from mice pretreated with various agents that induce cytochrome P450 were studied. When 1 mM caffeine was included, the rate of glutathione-APAP conjugate (GS-APAP) formation was increased significantly by 33 and 39% in microsomes from phenobarbital (PB)- and dexamethasone (DEX)-treated mice, respectively, whereas this parameter was decreased 39 and 12% by caffeine in microsomes from beta naphthoflavone (beta NF)- and acetone-treated mice, respectively. A 5 mM concentration of caffeine increased GS-APAP formation by 47, 107 and 117% in microsomes from control, PB-, and DEX-treated mice, respectively, and decreased it 39 and 25% in microsomes from beta NF- and acetone-treated mice, respectively. Caffeine was a competitive inhibitor of APAP bioactivation in microsomes from beta NF- and acetone-treated mice. While caffeine increased APAP bioactivation in microsomes from uninduced, PB-, and DEX-treated mice, the apparent Km values for APAP were increased by caffeine, indicating that this enhancement was not due to a direct effect of caffeine on APAP binding to cytochrome P450 but may be due to an effect of caffeine on the substrate-enzyme complex. The variable effect of caffeine on APAP hepatotoxicity correlated with the effect of caffeine on APAP bioactivation by liver microsomes, regardless of pretreatment. Lack of correlation of aminopyrine N-demethylase, but good correlation of erythromycin N demethylase activity with the extent of caffeine enhancement of APAP bioactivation following PB or DEX treatment suggests that a murine P450 subfamily similar to the rat P450 3A subfamily may be the candidate in mediating the stimulatory effect of caffeine on APAP bioactivation and APAP-induced hepatotoxicity. PMID- 8347174 TI - Transport of 5-fluorouracil and uracil into human erythrocytes. AB - The transport of 5-fluorouracil (5-FU) and uracil into human erythrocytes has been investigated under initial velocity conditions with an "inhibitor-stop" assay using a cold papaverine solution to terminate influx. At 37 degrees and pH 7.3, 5-FU influx was nonconcentrative; was partially inhibited by adenine, hypoxanthine, thymine, and uracil; and was insensitive to inhibition by nucleosides or inhibitors of nucleoside transport. Inhibition of the influx of 5 FU or uracil by adenine (3.0 mM) did not increase when other pyrimidines or inhibitors of nucleoside transport were combined with adenine. 5-FU and uracil exhibited similar saturable (Km approximately 4 mM, Vmax approximately 500 pmol/sec/5 microL cells) and nonsaturable (rate constant approximately 80 pmol/sec/mM/5 microL cells) components of influx. 5-FU, uracil, adenine, and hypoxanthine were competitive inhibitors of each other's influx with Ki values matching their respective Km values for influx. We conclude that 5-FU and uracil enter human erythrocytes at similar rates via both nonfacilitated diffusion and the same carrier that transports adenine and hypoxanthine. PMID- 8347175 TI - Modulation of benzene induced toxicity by protein A. AB - Administration of benzene (i.p. 1.0 mL/kg body weight) for 3 consecutive days produced leucopenia and lymphocytopenia in female albino rats. In addition, the total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly (P < 0.001) increased. Low molecular weight (LMW) bleomycin-detectable iron accumulated only in bone marrow. Prior administration of Protein A (PA), a multipotent immunostimulant and interferon inducer (60 micrograms/kg body weight, i.v. twice weekly for 2 weeks), ameliorated most of the adverse effects of benzene. PA restored the changes in hepatic histological architecture, reversed leucopenia and superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content of bone marrow were normalized. Isozymes of glutathione-S-transferase (alpha, pi, mu) which decreased following benzene exposure increased in PA pretreated benzene exposed rats. This study suggests that pretreatment with PA modulates the toxicity of benzene. PMID- 8347176 TI - Interaction of the orally active dianionic cephalosporin cefixime with the uptake system for oligopeptides and alpha-amino-beta-lactam antibiotics in rabbit small intestine. AB - The uptake of two orally active beta-lactam antibiotics of different chemical structure, the zwitterionic alpha-aminocephalosporin cephalexin and the dianionic carboxymethoxyimino-cephalosporin cefixime, by brush border membrane vesicles obtained from rabbit small intestine and their molecular interaction with the H+/oligopeptide transport system were investigated. The uptake of both compounds was stimulated by an inwardly directed H(+)-gradient with a profound pH-maximum for cephalexin at pH 6outside and pH 7.4inside whereas cefixime uptake was maximal below pH 5outside. Modification of histidyl residues of membrane proteins led to a complete loss of pH dependence of transport of both cephalosporins. The uptake of cephalexin was competitively inhibited by cefixime and dipeptides and vice versa that of cefixime by cephalexin and dipeptides. The uptake of cefixime was trans-stimulated by cephalexin and glycyl-L-proline whereas cephalexin uptake could only be trans-stimulated by glycyl-L-proline, not by cefixime. Photoaffinity labeling with [3H]benzylpenicillin as a direct photoaffinity probe of the H+/oligopeptide transport system demonstrated a direct molecular interaction of both cephalexin and cefixime with this transporter in the pH range of 5-8. Thermal pretreatment of membrane vesicles inhibited the cephalexin transport system temperature-dependently, whereas cefixime uptake was not inhibited, but stimulated. Taken together we conclude that dianionic cephalosporins like cefixime bind to the transport system shared by oligopeptides and alpha-amino-beta-lactam antibiotics. Their transport across the enterocyte brush border membrane, however, may occur to a significant extent by a different transport system. PMID- 8347178 TI - Glutathione and bile acid synthesis. II. Effect of hepatic glutathione content on the activity and mRNA levels of cholesterol 7 alpha-hydroxylase in the rat. AB - Hepatic cholesterol 7 alpha-hydroxylase (CH-7 alpha) activity in intact rats depleted of glutathione (GSH) was reduced significantly (P < 0.007) compared with that in untreated controls. Northern blot analysis of poly A+ mRNA isolated from GSH-depleted and control rat livers showed that there was a reduction in mRNA for CH-7 alpha in treated rats that was commensurate with the reduction in CH-7 alpha activity. The fact that the level of transferrin mRNA was unaltered by the depletion of GSH suggests that the change in steady-state CH-7 alpha mRNA content is specifically sensitive to GSH content. This observation extends previous in vitro findings and provides strong justification for a more detailed biochemical investigation into the interaction between GSH levels and the regulation of CH-7 alpha mRNA levels. PMID- 8347177 TI - Reversal of 6-mercaptopurine and 6-methylmercaptopurine ribonucleoside cytotoxicity by amidoimidazole carboxamide ribonucleoside in Molt F4 human malignant T-lymphoblasts. AB - Cytotoxicity of 6-mercaptopurine (6MP) and 6-methylmercaptopurine ribonucleoside (Me-MPR) was studied in Molt F4 human malignant lymphoblasts. Both drugs are converted into methylthioIMP (Me-tIMP), which inhibits purine de novo synthesis. Addition of amidoimidazole carboxamide ribonucleoside (AICAR) circumvented inhibition of purine de novo synthesis, and thus partly prevented 6MP and Me-MPR cytotoxicity. Purine nucleotides, and especially adenine nucleotides, were recovered by addition of AICAR. Under these conditions, Me-tIMP formation decreased. The results of this study indicate that formation of Me-tIMP may be important for 6MP cytotoxicity in Molt F4 cells. These data suggest that depletion of adenine nucleotides is the main cause for Me-tIMP cytotoxicity. PMID- 8347179 TI - Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). AB - BACKGROUND: The Lennox-Gastaut syndrome is a childhood disorder characterized by multiple types of seizures, mental retardation, characteristic electroencephalographic abnormalities, and resistance to standard antiepileptic drugs. Felbamate is an investigational antiepileptic drug with a preclinical profile that suggests it would be effective in patients with multiple types of seizures. In controlled clinical trials, felbamate was superior to placebo in reducing the frequency of refractory partial-onset seizures. METHODS: We studied the efficacy of felbamate in 73 patients ranging in age from 4 to 36 years who had the Lennox-Gastaut syndrome. During a 28-day base-line phase, the patients received their usual antiepileptic therapies. At the end of this phase, felbamate or placebo was administered for 70 days in addition to the current antiepileptic medications. The dosage of felbamate was titrated during the first 14 days of the treatment phase to a maximum of 45 mg per kilogram of body weight per day or 3600 mg per day, whichever was less. The primary efficacy variables were the total number of seizures counted during a four-hour period of video recording, parents' or guardians' global evaluations of the patients' quality of life, and the total number of atonic seizures, as reported by parents or guardians. RESULTS: The patients treated with felbamate had a 34 percent decrease in the frequency of atonic seizures, as compared with a 9 percent decrease in the patients who received placebo (P = 0.01). The felbamate-treated patients had a 19 percent decrease in the total frequency of seizures, as compared with a 4 percent increase in the placebo group (P = 0.002). The global-evaluation scores were significantly higher in the felbamate group than in the placebo group from day 49 to the end of the study. There were no significant differences in the frequency of seizures occurring during video monitoring, but there was a significant reduction (P = 0.017) in the number of tonic-clonic seizures during the maintenance period in the felbamate group. The types and frequency of side effects were similar in the two treatment groups. CONCLUSIONS: Felbamate is beneficial in patients with the Lennox-Gastaut syndrome. PMID- 8347180 TI - Therapeutic choices in the patient with coronary artery disease and left ventricular dysfunction. PMID- 8347181 TI - Fraud and malpractice in the context of clinical research. Working Party of the Medical Committee of the Association of the British Pharmaceutical Industry in May 1992. PMID- 8347183 TI - Ontario's move to limit out-of-province health care spending pays off in big way. PMID- 8347182 TI - Heparin in coronary artery disease: new uses for an old drug. AB - The role of heparin in the treatment of coronary artery disease remains unclear. Although of benefit in unstable angina and the prevention of acute occlusion following angioplasty, its value as adjunctive therapy in myocardial infarction is limited. Further studies are needed to assess the effect of heparin on angioplasty restenosis and late venous graft occlusion. PMID- 8347184 TI - Does integration of food animal production bode well for the future? PMID- 8347185 TI - Hemorrhagic complications attributable to certain drugs. PMID- 8347186 TI - A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts. AB - We have examined the effect of a synthetic low-molecular-weight matrix metalloproteinase inhibitor, [4-(N-hydroxyamino)-2R-isobutyl-3S- (thiopen-2 ylthiomethyl)-succinyl]-L-phenylalanine-N-meth yla mide (BB-94), on human ovarian carcinoma xenografts growing in nude mice. The xenografts grew as thick intraperitoneal mucinous ascites containing free-floating tumor cell clumps. The ascites increased in volume, causing death approximately 3 weeks after introduction. Treatment with BB-94 caused resolution of ascitic disease. Tumor burden was dramatically reduced, and survival increased 5-6-fold. The increase in survival was dose dependent. The effects observed with BB-94 appeared to be due to its matrix metalloproteinase inhibiting effects, inasmuch as its inactive diastereoisomer had no effect on tumor biology. Following treatment with BB-94, free-floating clumps of tumor cells became surrounded by a capsule of host cells. These clumps of tumor cells typically formed one small (approximately 8 mm) avascular tumor of bright white appearance loosely attached to fat in the peritoneum. Tumor cells within these capsules often appeared to be necrotic. Gel substrate analysis demonstrated that activated Mr 92,000 type IV collagenase was present in the xenografts. We propose that inhibition of this enzyme causes the transition of ascites to solid tumors, concomitantly slowing tumor cell growth and allowing the development of tumor stroma. PMID- 8347187 TI - Glutaraldehyde for biopsy forceps. PMID- 8347188 TI - Unassisted peripheral nerve blocks. PMID- 8347189 TI - Thyroid eye disease. PMID- 8347191 TI - Outcome of patients with depressed left ventricular function. PMID- 8347192 TI - Treatment of Parkinson's disease. PMID- 8347193 TI - Low CSF pressure. PMID- 8347194 TI - Laparoscopic abdominoperineal resection of the rectum. PMID- 8347190 TI - Low back pain. AB - The studies reviewed here show that the duration and severity of individual episodes of back pain can be lessened, reducing recurrences and their cost in terms of suffering and lost work. Frank examines differential diagnosis; acute, chronic, and intractable pain; and service implications. Modern management emphasises self care, and bed rest should usually not be longer than 48 hours. A return to physical fitness and other activities, including employment, is actively encouraged. Medication has a role in facilitating these objectives. Two points are especially emphasised: strategies to manage low back pain must be long term and preventive; and the responsibility to keep fit, maintain an exercise programme, and remain relaxed so as to avoid physically stressing the spine is that of the individual, not of the professionals. PMID- 8347195 TI - Laparoscopic cholangiography: a simple inexpensive technique using readily available materials. PMID- 8347197 TI - Primary prevention of malignant melanoma: to know may not be enough. PMID- 8347196 TI - Galaptin-mediated adhesion of human ovarian carcinoma A121 cells and detection of cellular galaptin-binding glycoproteins. AB - Previously, we have shown that galaptin, an endogenous beta-galactoside-binding lectin, is present in extracellular matrix where it may participate in the adhesion of A121 human ovarian carcinoma cells to extracellular matrix via interaction with specific cell surface carbohydrate receptors. We now report that A121 cells adhere to polystyrene plates coated with polymerized human splenic galaptin. The carbohydrate-mediated specificity of this adhesive interaction was demonstrated by inhibition with lactose. Additionally, treatment of A121 cells with neuraminidase increased cellular adherence by 30%, while beta-galactosidase treatment of cells decreased adherence by 65%. These findings prompted us to isolate and identify the cell surface galaptin receptor. In a Western blot of A121 cell extracts separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, 125I-labeled polymerized galaptin bound [corrected] to a unique cellular protein having a molecular mass of 110 kDa. This receptor was enriched by affinity chromatography using polymerized galaptin-Sepharose. Treatment of this material with N-glycanase ablated its galaptin-binding activity. In related studies, A121 cells metabolically labeled with [3H]glucosamine demonstrated a radiolabeled polymerized galaptin-binding protein with an identical molecular mass of 110 kDa. These studies confirmed the glycoprotein nature of this putative endogenous cellular galaptin receptor. Further studies with antibodies directed against two lysosomal associated membrane proteins, lamp-1 and lamp-2, demonstrated specific reactivity in Western blots with the 110-kDa glycoprotein. Additionally, 125I-polymerized galaptin recognized a 110-kDa protein in Western blots of material immunoprecipitated from A121 cell lysates by lamp-1 and lamp-2 antibodies. Finally, indirect immunofluorescence using antibodies directed against lamps detected cell surface antigenicity. Therefore, lamp-1 and/or lamp-2 appear to be the putative cell surface receptors involved in the adhesion of ovarian carcinoma cells to extracellular matrix mediated by galaptin. PMID- 8347198 TI - HIV-related thrombocytopenia. PMID- 8347199 TI - The American Health Care System--Medicare. PMID- 8347200 TI - Postoperative pulmonary function abnormalities after coronary artery bypass surgery. PMID- 8347201 TI - Abruptio placentae and very high parity. PMID- 8347202 TI - Laparoscopic radical hysterectomy. PMID- 8347203 TI - Alpha-tocopherol levels in parkinsonian brains. PMID- 8347204 TI - Promoting healthy eating. PMID- 8347205 TI - Disagreeing on how to treat CFS patients. PMID- 8347206 TI - Bad teeth and myocardial infarction. Biological mechanisms for link. PMID- 8347207 TI - The thrifty genotype in non-insulin dependent diabetes. PMID- 8347208 TI - Non fund-holding a positive choice. PMID- 8347209 TI - Low back pain. Smoking linked to back pain. PMID- 8347210 TI - Nazi medicine. PMID- 8347211 TI - Nazi medicine. PMID- 8347212 TI - Aid to developing countries. PMID- 8347213 TI - Upper gastrointestinal bleeding in the critically ill. PMID- 8347214 TI - Primary pyogenic abscess of the psoas muscle. PMID- 8347215 TI - Cognitive neuropsychology is more than single-case studies. AB - S. M. Sokol et al. (1991) claim that "The Cognitive Neuropsychology Approach" (p. 355) is limited to the single-case study design. The present article takes issue with this claim. Contrary to the beliefs of Sokol et al., we argue (a) that cognitive modularity is best studied by group design, (b) that the possibility of neural reorganization in patients should be tested through converging evidence from different populations using various methods, and (c) that cognitive neuropsychology can benefit from being a part of cognitive neuroscience where both neural and cognitive mechanisms underlying normal cognition are relevant. PMID- 8347216 TI - The 'do not resuscitate' decision. PMID- 8347217 TI - Sympathetic-nerve activity during sleep. PMID- 8347218 TI - Diltiazem in the prevention of coronary artery disease in heart-transplant recipients. PMID- 8347219 TI - Skeptical about importance of low levels of lead. PMID- 8347220 TI - Single-payer system. PMID- 8347221 TI - Re: Asbestos and cancer, 1934-1965. PMID- 8347222 TI - The effect of repositioning error on serial magnetic resonance imaging scans. PMID- 8347223 TI - 'Rubber dam usage related to restoration quality and survival'. PMID- 8347224 TI - Microvascular abnormalities in the mucosal prolapse syndrome. PMID- 8347225 TI - Neurogenic pulmonary edema. PMID- 8347226 TI - Isolation of Mycobacterium malmoense from HIV-positive patients. PMID- 8347227 TI - Benign relapsing meningo-encephalomyelitis. PMID- 8347228 TI - Obstetrical lumbosacral plexus injury. PMID- 8347229 TI - Eradication of Helicobacter pylori in recurrent duodenal ulcer. PMID- 8347230 TI - Drowning. PMID- 8347231 TI - Vaginosonography and chorionic villus sampling (CVS) PMID- 8347232 TI - Response to Graber editorial. PMID- 8347233 TI - Issues that hamper efforts to integrate information systems. PMID- 8347234 TI - Respiratory home care: the importance of multidisciplinary collaboration. PMID- 8347235 TI - The law and control of tuberculosis. PMID- 8347236 TI - Early systolic compliance peak/reflective-wave complex. PMID- 8347237 TI - Intravenous oxygenator use in adult respiratory distress syndrome. PMID- 8347238 TI - Management of the severely anemic Jehovah's Witness. PMID- 8347239 TI - Fine-needle aspiration of salivary glands: its utility and tissue effects. PMID- 8347240 TI - Ventricular aneurysmectomy and coronary artery ligation: an alternative method of treatment of ALCAPA syndrome. PMID- 8347241 TI - Late-onset rhegmatogenous-traction retinal detachment due to Candida chorioretinitis. PMID- 8347242 TI - Treatment of oral cancer by interstitial irradiation using iridium-192. PMID- 8347243 TI - Semen cryobanking for men with cancer. PMID- 8347244 TI - Labial tumors in angelfish. PMID- 8347245 TI - Pruritic urticarial papules and plaques of pregnancy. PMID- 8347246 TI - Comments on halothane gene carriers in pigs. PMID- 8347247 TI - [Characteristics and mechanisms of action of leukocyte depletion filters]. AB - Since their creation, leukocyte depletion filters, used to prepare leukocyte-poor red cell or platelet concentrates, have been continuously evoluting: their volume has been reduced and their composition has been modified, polyester fibers have replaced cotton wool or cellulose acetate. In the same way, their capacity to remove leukocytes has increased. The mechanisms of cell separation are still unclear. Through published studies, different factors seem to be implicated, such as wetable surface of the filter, surface tension or charge density of fibers. It was also observed that removal of lymphocytes from red cell concentrates is rather based on trapping in the fiber network, and that removal of granulocytes, monocytes and platelets is partly due to activation and subsequent adhesion to the fibers. There have been few studies of the mechanism of leukocytes depletion from platelets concentrates. PMID- 8347249 TI - [Assessment of filtration performance]. AB - The technique of filtration which has constantly been improved over past years makes it possible to obtain highly pure blood products (the rate of leukocyte depletion can reach 3 to 5 log). Several study groups (BEST, PSL) and international committees of experts have defined a number of standards with which leukocyte depleted blood products must comply. Assessment of filtration procedures is thus made necessary, it applies to the different steps of the filtration procedure: preparation techniques of red cell or platelet suspension, priming and rinsing of the filter. Likewise a number of parameters have to be checked: filtration time, temperature, age of suspensions. Moreover quality control procedures must be implemented, using adapted and validated measuring methods (Nageotte hemacytometer, for instance). The parameters to be monitored include the number of residual leukocytes, (mean value: 1 x 10(6), i.e. about 4 WBCs/microliters), and the rate of hemoglobin or platelet recovery. Any new filtering equipment or material must satisfy strict requirements and standards including clinically acceptable limits as part of the same quality approach. Validation, in this case, consists in determining the maximal leukocyte content which the filter can absorb (capacity) and the average rate of leukocyte removal (efficacy). The constant monitoring of filtration performance contributes to improving the quality of red blood cell or platelet suspensions and thus meet clinicians' requirements for their patients. PMID- 8347248 TI - [Filtration technology]. AB - The leukocyte removal technology of platelet and red blood cell concentrates is now based on the only method: the filtration. In order to perfectly control this technology, it is necessary to know the different parameters that interfere in the quality of the leukocyte removal. These different parameters are studied here. They are classified in two types: the parameters that are related to the concentrate to filtrate: method used for the preparation, age, state (temperature, aggregates), concentration of red blood cells, platelets and leukocytes; the parameters that are related to the leukocyte removal technology and to the different steps of its carrying out: filter type (composition, size, geometry), prefilter, priming of the filter, flow rate during the filtration, rinsing and centrifugation after the filtration, elimination of the air inside the filter and the filtered concentrate, sterile connections, and finally good behavior in front of the difficulties and hitchs that could occur during the filtration procedure. PMID- 8347250 TI - [Filtration of platelet concentrates. Technical aspects, quantitative results. Group PSL]. AB - This work summarizes a multicentric study (20 Blood Transfusion Centers) concerning the use of different filters applied to platelet collection. The results are good with the different filters and platelets concentrates evaluation. Nevertheless, we have seen a great heterogeneity of platelet concentrates. This characteristic could explain the variability in filter performances. Maybe we have to adapt some type of filter with specific platelet concentrates. In conclusion, it is important to continue the evaluation of new platelet concentrate filters, in order to increase the performances and the filtration quality. Clinical trials seem to be useful in the future to appreciate the effects of filtered platelets on alloimmunization and CMV transmission. PMID- 8347251 TI - [Leukocyte depletion of blood products and anti-HLA immunization]. AB - HLA alloimmunization and subsequent refractoriness to platelet transfusions are frequent complications of transfusion therapy in patients with hematologic malignancies. Contaminating leukocytes in red cell and platelet concentrates are responsible for primary HLA alloimmunization. In many clinical trials, it has been demonstrated that the use of leukocyte-poor blood products prepared by filtration could reduce HLA-alloimmunization from 40% to 15%. The immunogenic level cannot be determined accurately, but the previous studies show that a residual contamination below 1.10(6) leukocytes was efficient to prevent primary alloimmunization. Leukocyte depletion does not avoid secondary responses in patients having an history of pregnancies or transfusions. The UV-B irradiation of platelet concentrates, in combination with filtration, should further reduce alloimmunization in these presensitized patients. PMID- 8347252 TI - [Leukocyte depletion of blood products and transfusion tolerance]. AB - Leukodepletion of red blood cell or platelet concentrates decreases significantly the number of febrile non hemolytic transfusion reactions. Filtration appears to be very efficient on red blood cell transfusion reactions while its effect with platelet concentrates remains variable. PMID- 8347253 TI - [Effect of leukocyte depletion on preservation of erythrocyte and platelet concentrates]. AB - Early leukocyte depletion suppresses metabolic or cellular changes which they involve during red blood cell or platelet concentrates storage. The evolution of the cellular alteration control parameters and of the storage media content is modified by leukocyte concentration of blood products. PMID- 8347254 TI - Comparative analysis of DNA ploidy and proliferative index in fine needle aspirates of non-Hodgkin's lymphomas by image analysis and flow cytometry. AB - To determine the application of image analysis (IA) to fine needle aspiration (FNA) of non-Hodgkin's lymphomas, 78 cases, categorized according to the Working Formulation, were analyzed and compared with those analyzed by flow cytometry (FCM). Aspirated material was immediately fixed in either IA fixative (31 cases) or acetone, stored at -70 degrees C (47 cases) for periods up to 48 months and postfixed in IA fixative. IA assessed DNA index (DI), ploidy balance, degree of hyperdiploidy and proliferation index (PI). DNA index, % S + G2M and RNA index were obtained by acridine orange FCM. There were no significant differences in measured variables between fresh and stored cases. Statistically significant differences between low, intermediate and high grade lymphomas were present in all evaluated variables except DNA ploidy (DI) (P = .074) measured by IA. DI, however, showed a very high correlation with the DI obtained by FCM (r = .94). PIs, although generally lower, also had a high correlation with S + G2M (r = .85). We conclude that results obtained by IA were comparable to results by FCM and that frozen material can be used to retrospectively evaluate ploidy and proliferation. IA is especially suitable for the evaluation of low-volume specimens obtained by FNA. PMID- 8347255 TI - Comparison of DNA content in primary and lymph node metastases in prostate adenocarcinoma. AB - There is increasing evidence that nuclear DNA content has significant prognostic value for adenocarcinoma of the prostate. There also appear to be considerable differences in cellular DNA content between patient cohorts when primary tumor or pelvic lymph node metastases are measured. In addition, prostate adenocarcinoma is heterogeneous in DNA measurements; that adds confusion to studies incorporating fine needle aspiration biopsy samples. We compared cellular DNA content in 34 patients with available needle biopsies and pelvic lymph node metastases. Four groups of patients were identified: diploid-range primaries and metastases (8 patients), diploid-range primaries and aneuploid metastases (13), aneuploid primaries and metastases (10), and aneuploid primaries and diploid range metastases (2). Patients with diploid-range primary tumors had a longer interval to progression and death than did patients with aneuploid primary tumors, although neither was significant in this small series. Patients with diploid-range lymph node metastasis had a longer interval to progression (P = .04) and survival (P = .09) than did individuals with aneuploid metastases. We conclude that the cellular DNA content of prostate cancer metastases in this series of stage D1 patients was more powerful in predicting time to progression and ultimate survival than evaluation of needle biopsy specimens of the primary cancer. PMID- 8347256 TI - Textural analysis of lymphoid cells in serous effusions. A mathematical morphologic approach. AB - Nuclear texture of reactive and well-differentiated neoplastic lymphocytes from serous effusions was studied by an approach based on principles of mathematical morphology. Density features were obtained before and after gray level nuclear image transformation by morphologic closing (dilation followed by erosion) and application of a top-hat function, which detects light or dense spots with a determined width and contrast. Five cases of benign reactive lymphocytic serous effusions and 11 cases of effusions in well-differentiated lymphocytic lymphomas were analyzed retrospectively. Each lymphoid cell was characterized by 24 densitometric features. Rank-order transformation was used for linear discriminant analysis given non-normal distributions of variables. In a first model formed by pooling all cells, discriminant function distinguished between 110 reactive and 216 malignant lymphocytes in the learning set and between 111 reactive and 226 malignant lymphocytes in the test set with better than 81% accuracy in both. In a second model, correct classification of cases as reactive or malignant was achieved in 5/5 reactive and 11/11 malignant lymphoid effusions. The results indicate that mathematical morphologic transformations of the gray level image may be an effective adjunct to other textural descriptors of cellular atypia, especially in the differential diagnosis of lymphoid serous effusions. PMID- 8347257 TI - Proliferation markers in non-Hodgkin's lymphoma. A comparative study between cytophotometric quantitation of Ki-67 and flow cytometric proliferation index on fine needle aspirates. AB - Proliferation markers appear to predict biologic behavior and responses to therapy in non-Hodgkin's lymphoma (NHL). We examined the value of the antibody against Ki-67, a marker for cycling cells, in 73 fine needle aspirates and compared these results with parameters of ploidy, DNA, RNA and proliferative index (PI) derived from acridine orange flow cytometry. NHLs were classified into three grades according to the Working Formulation. A fourth miscellaneous group, consisting of atypical lymphoid hyperplasia, was also analyzed. Ki-67 expression was quantitated on a single Cytospin sample from each FNA specimen using an image analysis quantitation software program based on measurement of optical density in the labeled structures. An average of 680 cells distributed through 10 random files was digitized per specimen. The mean Ki-67 positivity and PI calculated for each lymphoma grade were significantly different between grades (P < .0001), while the overall correlation between Ki-67 positivity and PI was high (r = .8). There was no correlation between grade and mean optical density of Ki-67, DNA and RNA, but Ki-67 positivity strongly correlated with PI (r = .8). These results are similar to those of previous studies performed on histologic sections of NHL in which the Ki-67-positive labeling index, measured by either visual scoring or image analysis, correlated positively with increasing grade of lymphoma according to both the Kiel classification and the Working Formulation. We conclude that Ki 67 staining of NHL provides information equivalent to that of PI and is useful for small specimens, such as fine needle aspirates. PMID- 8347258 TI - DNA ploidy in human colorectal adenocarcinomas. AB - Image cytometric determination of DNA content was performed on 207 colorectal adenocarcinomas surgically resected from 205 patients. Of these 207 tumors, 193 (93.2%) showed an aneuploid DNA distribution pattern, whereas the remaining 14 (6.8%) exhibited a DNA pattern corresponding to that found in proliferating diploid populations. The DNA content of 20 of these colorectal carcinomas was also studied by flow cytometric measurements on deparaffinized, disintegrated material. Flow cytometric measurement detected aneuploidy in only 9 of these 20 (45%) tumors, whereas 17 of the same 20 (85%) carcinomas showed aneuploidy when using image cytometric measurement on imprints. These results suggest that colorectal carcinomas are either aneuploid (vast majority) or proliferating diploid and that image cytometric DNA measurement on histologically controlled material is superior to flow cytometric measurement. PMID- 8347260 TI - Quantitative immunohistochemistry of parvalbumin expression in the rat diaphragm. AB - Parvalbumin is a calcium-binding protein involved in the mechanism of Ca++ exchange between sarcoplasmic reticulum and the myofibrils. This characteristic promotes a direct correlation between the amount of parvalbumin and the velocity of contraction-relaxation of skeletal muscle fibers. To quantify the expression of parvalbumin in the rat diaphragm, transverse paraffin sections of this muscle were processed immunohistochemically using antiparvalbumin monoclonal antibody. The stained sections were inspected on an image analysis device to evaluate the intensity of the immunoreaction and to make morphologic measurements of the muscle fibers. The immunoreaction intensity data allowed the division of fibers in fast- and slow-twitch types. The rat diaphragm was characterized as a fast twitch muscle due to the presence of 59.8% of fast-twitch fibers. The fibers' lesser diameter values showed that the slow-twitch fibers had a small diameter as compared to the fast-twitch ones (P < .001). The method used suggests that immunohistochemistry for parvalbumin assisted by image analysis is a feasible technique to separate fast- and slow-twitch skeletal muscle fibers in paraffin sections and to characterize their morphologic profiles. PMID- 8347259 TI - Variations associated with disaggregation methods in DNA flow cytometry. AB - We investigated the variations in DNA ploidy by flow cytometry (FC) among cell suspensions acquired by different disaggregation methods from the same tumor specimens. Cell suspensions (n = 121) of 40 solid tumors were obtained by mechanical mincing (n = 33), enzymatic digestion (n = 19), in vitro fine needle aspiration (FNA) (n = 34) or scraping (n = 35) of the tumor tissues. Mechanical disaggregation gave the highest cell yield, whereas enzymatic digestion provided the best cell viability. The mean values for the G0/G1 coefficient of variation, DNA indices and percent S phase were not significantly different in cell suspensions obtained with the four methods. However, the yield of malignant cells ranged from 60.4 +/- 5.3% (SEM) (enzymatic) to 82.3 +/- 3.1% (scraping). Tissue aliquots of 32 tumors were disaggregated by three to four methods, and the combined results of DNA ploidy obtained from different cell preparations showed that 22 tumors were nondiploid, but concordance with an abnormal DNA peak was found in only 27.3% (6/22) of the DNA nondiploid tumors. Our results indicate that scraping tumor tissue appears to be the best method for DNA FC since it has the highest percentage (61.3) of DNA nondiploid clones. Also, we believe the multiple samplings may provide comprehensive information on the DNA ploidy of solid tumors. PMID- 8347261 TI - Image cytophotometric DNA histogram heterogeneity in adenocarcinoma of the breast. AB - In 36 breast carcinomas, DNA histograms derived from the edge of an invasive primary tumor were compared with those of a second area in the invasive tumor (n = 10) or of corresponding in situ (n = 22) and/or (nodal) metastatic (n = 6) components using image cytophotometry on formalin-fixed, paraffin-embedded sections. DNA aneuploidy (defined by comparison with diploid host stroma cells) was identified in the invasive areas of 26/36 (72%), the noninvasive foci of 16/22 (73%) and the metastases of 5/6 (83%). Ploidy status of different areas of invasive tumor were concordant in all (10/10) cases; however, the in situ and invasive areas exhibited different DNA content determinations in 5/22 (23%), and metastases differed from the primary neoplasm in 3/6 (50%). Moreover clonal DNA content heterogeneity, defined as the presence of more than one discrete G0/G1 population, was observed in 20/36 (56%) tumors examined. Clonal heterogeneity was generally manifest as bimodal DNA histograms in one (n = 11) or both (n = 4) components of a tumor. Also, most DNA histogram heterogeneity was due to the presence of diploid range (n = 11) or near-tetraploid (n = 6) neoplastic populations accompanying DNA aneuploid clones. The remaining heterogeneous cases were unimodal in both components analyzed but exhibited aneuploid stemlines with different DNA indices (n = 2) or a diploid range population in one histogram and an aneuploid population in the other (n = 3). We conclude that DNA content heterogeneity is frequent in breast carcinoma and, in large part, may be accounted for by near-diploid or near-tetraploid stemlines, which are difficult to resolve from benign host elements in flow cytometric histograms. PMID- 8347262 TI - Quantitative effects of intercellular signals on computer-simulated tumor patterns. AB - The behavior of tumor cells within a particular in vivo microenvironment is considered to be regulated by intercellular signals. Previous studies of computer simulations of tumor growth demonstrated a qualitative effect of autocrine and paracrine signaling factors on the resulting morphologic patterns. We investigated the quantitative effect of these intercellular signals when the evolving patterns were evaluated by a set of pattern analysis procedures, yielding 18 quantitative morphologic features. The results show that both autocrine and paracrine factors regulating either tumor cell proliferation, motility or death influenced at least 10 of the 18 features significantly (linear regression analysis; n = 50 for each experiment; P = < .01). Furthermore, multivariate analysis of 600 simulated patterns also demonstrated highly significant relationships between intercellular signals and quantitative features of the evolving pattern (P = < .001). The study showed that various pattern measurement features indicate a direct influence of intercellular signals on tumor patterns in computer simulations. PMID- 8347263 TI - Fine needle aspiration diagnosis of renal oncocytoma. A mathematical morphologic approach. AB - Differentiation between renal oncocytomas and well-differentiated oxyphilic cell renal carcinomas from fine needle aspiration cytology smears may present considerable difficulties. To better define diagnostic criteria, we used high resolution architectural characteristics of nucleus and cytoplasm based on mathematical morphologic concepts. Particulate structural elements were selected for their size and optical density by the so-called top-hat function. Spatial density, size distribution and a function of distance between particles were computed. We quantitated cellular samples from fine needle aspirates obtained from 10 renal oncocytomas and 5 well-differentiated oxyphilic cell renal carcinomas. In two of the former, cytologic diagnosis was doubtful. Subsequent removal of the tumor and its histologic examination established the final diagnosis in all cases. Stepwise discriminant analysis correctly classified all cases as oncocytomas or renal carcinomas, although the results need to be considered with caution due to the necessarily limited number of observations. Multivariate graphic representation by star glyphs clearly depicted the differences between oncocytoma and oxyphilic cell renal carcinomas and the abnormal characteristics of two oncocytoma cases misclassified initially. PMID- 8347264 TI - Effect of cooling rate and its interaction with pre-freeze and post-thaw tissue culture on the in vitro and in vivo function of cryopreserved pancreatic islets. AB - Rapid cooling destroys passenger lymphoid cells during cryopreservation. We now describe improved in vivo survival of rat islets after rapid cooling by adding pre-freeze tissue culture. Islets were equilibrated with 2M dimethylsulphoxide, cooled at 0.3 degrees, 20 degrees, or 70 degrees C/min, and stored at -196 degrees C. The culture was kept at 37 degrees C for 2 or 72 h before and/or after preservation. When cooled at 0.3 degrees C/min, keeping the culture for 72 h gave the highest proportion of dye-excluding cells, but more than 50% were viable under all culture conditions. Islets cooled at 20 degrees or 70 degrees C/min (rapidly) required 72 h of culture for a survival rate of more than 50%. When islets were cultured for 72 h before cryopreservation, their in vitro insulin secretory ability was similar to that of slowly cooled islets and they were able to sustain normoglycaemia in diabetic animals, although more islets were needed. Extended tissue culture before freezing improves the survival of rapidly cooled islets and is therefore important for combined immunomodulation and cryopreservation. PMID- 8347265 TI - Transplantation of shipped donor livers. AB - Between September 1988 and November 1991, 201 donor hepatectomies and transplantations were performed. Fifty-four livers (26.9%) were harvested by other teams and shipped for transplantation; 147 livers (73.1%) were procured by teams from our transplant center. Comparing the maximal postoperative serum aminotransferases (s-AT), we evaluated the postischemic damage of shipped organs (AST 951 +/- 931 IU/l; ALT 820 +/- 666 IU/l) and nonshipped organs (AST 753 +/- 1256 IU/l; ALT 636 +/- 896 IU/l); this did not differ significantly. Donor related factors, such as critical parameters (i.e., cardiac arrest, arterial hypotension, age over 50 years, or elevated preoperative s-AT), length of stay in the intensive care unit before harvesting, and cause of death showed similar patterns in both groups. The mean cold ischemia time in the group of shipped livers (12 h 10 min +/- 4 h 22 min) and in the nonshipped livers (10 h 6 min +/- 3 h 53 min) did not differ significantly. Five cases (2.5%) of a primary non functioning graft presenting with significantly (P < 0.001) elevated s-AT (AST 4944 +/- 2280 IU/l; ALT 3186 +/- 1918 IU/l) necessitated an early retransplantation. One organ was shipped and four organs were nonshipped, thus corresponding to their portion of all grafts. These data indicate that the transplantation of shipped livers is a safe procedure procedure, provided that procurement is done by experienced centers. PMID- 8347266 TI - The influence of primary non-function on the accuracy of ultrasound measurements in the diagnosis of renal allograft rejection. AB - Daily ultrasonographic measurements of transplant cross-sectional area were used to quantify allograft swelling as a diagnostic test for acute rejection in a series of 120 renal transplants. Initial graft function (IF) occurred in 86 patients (72%) and primary non-function (PNF) occurred in the remaining 34 (28%). An increase in allograft cross-sectional area greater than or equal to 10% was defined as a positive ultrasound scan suggesting an acute rejection episode and was investigated by needle core biopsy. During periods of PNF, allografts with consistently negative ultrasound scans were submitted to needle core biopsy on a weekly basis. The diagnosis of rejection was based exclusively on the histological findings. In the IF group, agreement between ultrasound and histological diagnosis was good (k = 0.63, sensitivity 81%, specificity 83%, positive predictive value 76%, negative predictive value 86% and overall accuracy 82%). In the PNF group, agreement between ultrasound and histology was only fair (k = 0.46, sensitivity 77%, specificity 70%, positive predictive value 69%, negative predictive value 78% and overall accuracy 73%). It is concluded that a degree of allograft swelling is sometimes associated with acute tubular necrosis, and this makes ultrasound measurements of transplant size a less useful technique of monitoring kidneys with PNF. PMID- 8347267 TI - Effect of enalapril on proteinuria after kidney transplantation. AB - We studied the effect of enalapril, an inhibitor of angiotensin-converting enzyme (iACE), on proteinuria and renal function in recipients of renal allografts. Twenty-two patients with post-transplant nephrotic syndrome were treated with incremental doses of enalapril for 1 year. Urinary protein excretion decreased after 2 months of treatment from a mean of 8.9 g/day (range 4.0-18.9 g/day) to 4.5 g/day (range 0.4-10.0 g/day; P < 0.01) and remained significantly low for the rest of the study. However, in the same period, creatinine clearance did not change significantly; it went from 47.8 ml/min (range 17.1-110.3 ml/min) before treatment to 44.2 ml/min (range 16.5-88.5 ml/min) after 2 months of iACE therapy. Analysis of individual data showed that there was a significant reduction in proteinuria in 14 of the 22 patients and that the rate of deterioration of renal function did not increase in 17 of the 22 patients. We did not observe any serious side effects of enalapril administration. The results of our study prove that iACE can be used safely and effectively to reduce post-transplant proteinuria. PMID- 8347268 TI - Injury to cultured liver endothelial cells during cold preservation: energy dependent versus energy-deficiency injury. AB - Previously, we demonstrated an energy-dependent injury to cultured liver endothelial cells during cold incubation in University of Wisconsin (UW) solution. Here, the effects of Histidine-Tryptophan-Ketoglutarate (HTK) and Euro Collins (EC) solutions on these cells were studied. In HTK solution, 83% +/- 4% of the cells had lost viability after 9 h of incubation at 4 degrees C. The addition of cyanide (1 mM) to simulate hypoxic conditions protected the cells to the extent that only 9% +/- 1% of the cells lost viability over the same period; the addition of glucose (10 mM) led to increased cell injury. ATP levels were highest in the incubations with the most rapid loss of viability. In Krebs Henseleit buffer and EC solution, in contrast, cell injury increased upon addition of cyanide; the addition of glucose to Krebs-Henseleit buffer decreased injury. We conclude that the injury to cultured liver endothelial cells during cold incubation in HTK solution is energy-dependent, as it is in UW solution, whereas cells behave differently in EC solution and Krebs-Henseleit buffer. PMID- 8347269 TI - Is there an optimal time for the first cyclosporin dose in renal transplantation? AB - It is customary for patients undergoing kidney transplantation to receive their first dose of cyclosporin either just before or during the transplant operation. This ensures the early establishment of good levels of immunosuppression but might depress early graft function and contribute towards the development of acute tubular necrosis. In a controlled clinical trial, we have studied the effects of withholding cyclosporin for 12 h in patients undergoing cadaveric renal transplantation. Consecutive adult recipients of a cadaveric renal transplant were randomised to receive their first dose of cyclosporin (10 mg/kg p.o.) 6 h prior to transplant surgery or 12 h afterwards. All patients received azathioprine (1.5 mg/kg i.v.) and methylprednisolone (0.5 g i.v.) in addition during surgery. From the 2nd day onwards both groups were treated with an identical triple immunosuppressive regimen. The 27 patients who received their first dose of cyclosporin post-operatively had significantly better immediate and subsequent function than did the 26 patients who received their cyclosporin at the time of surgery. The delayed dosing was associated with improved graft survival and no increase in the frequency of rejection episodes. This regimen is recommended for all patients receiving triple therapy. PMID- 8347270 TI - Selection criteria for liver donation: a review. AB - An overview of the criteria that are currently being used for the selection of liver donors is presented. The validity of the different criteria is discussed. The potential benefits of introducing other modalities is dealt with. PMID- 8347272 TI - Percutaneous transhepatic embolization of an intrahepatic pseudoaneurysm following liver biopsy in a liver transplant patient. AB - A 41-year-old liver transplant patient had severe hemobilia from an intrahepatic pseudoaneurysm secondary to a liver biopsy. Selective intra-arterial embolization was not technically possible due to marked redundancy and tortuosity of the allograft hepatic artery. The pseudoaneurysm was localized by ultrasound and embolized using a direct percutaneous transhepatic approach. This is a novel way of approaching hemobilia in liver transplant patients after liver biopsy and may avoid the risks of arterial embolization. PMID- 8347271 TI - Protective effect of the PAF antagonist BN 52021 in an experimental renal warm ischemia model. AB - Platelet activating factor is involved in warm ischemic damage. We studied the effect of the PAF receptor antagonist BN 52021 in an experimental model of 60 min of renal warm ischemia in which the left kidney was flushed with Euro-Collins solution and a right nephrectomy was performed. Eighty Wistar rats were divided into a sham-operated group, two control groups, and four study groups, according to the dosage and route of BN 52021 administration. BN 52021 was used in the flush solution at concentrations of 0.1 and 0.5 mg/ml, or intravenously prior to ischemia at 5 and 10 mg/kg body weight. Creatinine clearance per 100 g body weight, fractional sodium excretion, and conventional histology were studied. Rats that received BN 52021 intravenously showed a significantly higher creatinine clearance than controls. Intravenous BN 52021 produced a higher acceleration of renal function recovery at 10 mg/kg than at 5 mg/kg body weight. Conventional histology was better in animals that received BN 52021 at 10 mg/kg body weight than in controls. Addition of BN 52021 to Euro-Collins flushing solution showed no protective effect. We conclude that intravenous BN 52021 shows a renal protective effect against warm ischemia. PMID- 8347273 TI - Homograft replacement of the aortic valve after liver transplantation. PMID- 8347274 TI - Copper and gene regulation in yeast. AB - The essential trace element copper is also highly toxic when accumulated at high intracellular levels. Copper detoxification in the yeasts S.cerevisiae and C.glabrata is carried out, in large part, by small, cysteine-rich metal binding proteins known as metallothioneins (MTs). The biosynthesis of yeast metallothioneins, the S.cerevisiae copper, zinc superoxide dismutase, and presumably other important copper homeostatic proteins, is transcriptionally induced by elevated environmental copper concentrations through the action of copper metalloregulatory transcription factors (MRTFs). Copper coordination drives the formation of a structure distinct from the apo-protein, whereupon the DNA binding function of MRTFs is activated. The copper MRTFs, ACE1 from S.cerevisiae and AMT1 from C.glabrata, directly interact with specific copper responsive cis-acting elements in the promotor regions of their respective target genes. The binding of copper, as a polynuclear cluster, to MRTFs provides a sensitive and rapid means of transducing the extracellular metal signal to activate gene transcription. PMID- 8347275 TI - An enzymatic method for zinc determination in serum. AB - In this study, serum Zn(2+) content was determined by a new enzymatic method. The method depends on the reactivation of apocarbonic anhydrase proportional to the Zn(2+) content of the sample. Carbonic anhydrase was purified from bovine erythrocytes by affinity chromatography. The Zn(2+) in its structure was removed by dialysis against pyridine 2,6-dicarboxylic acid, resulting in a pure apoenzyme with a yield of 100%. The activity of the enzyme was determined by its esterase effect on 4-nitrophenyl acetate. Zn(2+) levels were determined in the serum samples obtained from 100 healthy subjects, 10 patients with cirrhosis, 12 diabetic patients and 15 patients with chronic renal failure by this enzymatic method and by atomic absorption for comparison. There was a good correlation between the two methods in all patients and controls and intraassay CV% was 2.4 and 4.2 for enzymatic and atomic absorption methods, respectively and interassay CV% as 3.9 and 6.1 respectively. PMID- 8347276 TI - Synergistic bombesin and insulin stimulation of DNA synthesis in human fetal kidney in serum-free culture. AB - The respective influences of growth factors during kidney development can be directly evaluated using the chemically-defined serum-free culture system perfected in our laboratory. Since, in this culture model, conditions are minimal for growth and differentiation, DNA synthesis sharply decreases during the first 48 h. The addition of epidermal growth factor (EGF, 100 ng/ml), insulin (5 micrograms/ml) and transferrin (5 micrograms/ml) significantly restores this important cellular function. The objective of the present study was to determine the influence of bombesin, a potent mitogen, supplemented alone or in combination with insulin, transferrin and/or EGF. Cortical explants of human fetal kidneys (17-20 weeks) were maintained during 5 days in culture. When compared with 5 day controls (L-15 medium only), bombesin generated a maximal though weak effect on DNA synthesis at a concentration of 0.3 nM, corresponding to a stimulation index (SI) of 22%. When combined with either transferrin or EGF, or with transferrin plus EGF, bombesin did not alter the SI of individual factors. Insulin, in turn, greatly increased DNA synthesis (SI = 169%), while bombesin strongly potentiated this effect (SI = 275%). Transferrin also enhanced insulin SI from 169 to 240%. When added as a third factor, bombesin further potentiated the effectiveness (SI = 338%) of the combination insulin plus transferrin. These results indicate that bombesin controls cell proliferation in synergism with other regulators and hence may act as a competence growth factor during nephrogenesis. PMID- 8347277 TI - Transcriptional control of the platelet-derived growth factor subunit genes. AB - Platelet-derived growth factor (PDGF) is a potent mitogen consisting of heterodimers of two distinct but homologous polypeptide chains, denoted A and B. PDGF-like homodimers of the A- and B-chains have been isolated, as well as two distinct receptor types (alpha and beta), which discriminate among the PDGF isoforms. The PDGF A- and B-chains are encoded by distinct genes located on human chromosomes 7 and 22, respectively. Although PDGF has been implicated as an important participant in development, tissue repair, and numerous pathologic states including tumorigenesis, atherosclerosis and inflammation, the mechanisms which determine the rate of its synthesis are only beginning to be understood. Basal expression of the PDGF A- and B-chain genes has been characterized in a number of cell types and is directed in part by elements in the respective proximal promoter-regulatory regions of the two genes. In addition, the first intron of PDGF-B has been shown to contain both positive and negative regulatory elements. Transcription of the PDGF subunit genes is inducible by a wide variety of mitogenic growth factors, cytokines and other agonists. These agents produce a rapid increase in steady-state concentrations of PDGF A- and B-chain mRNAs, peaking within 4-8 h of stimulation. The inductive effects of protein kinase C activating phorbol 12-myristate 13-acetate (PMA), thrombin and transforming growth factor-beta (TGF-beta) are mediated through increases in the transcription rates of both genes. In addition, cAMP blocks the increases in transcription of the B-chain gene induced by thrombin and TGF-beta. Studies have demonstrated the importance of sequences immediately upstream of the B-chain transcription start site for induction in response to PMA-initiated megakaryocyte differentiation, an effect which is dependent on protein synthesis. However, cis-acting elements which mediate more rapid transcriptional induction seen in endothelial cells and astrocytes have yet to be identified in the proximal 5'-flanking sequences of either the A- or B-chain genes, suggesting that such events may be mediated by elements located outside of this region. PMID- 8347278 TI - Biological effects of saffron. AB - This review examines the literature data concerning the biological activities of saffron extract. Numerous studies have revealed that this substance possesses cytotoxic, anticarcinogenic and antitumor properties. A brief description of the other biological effects as well as chemical composition of the saffron extract is also included. Finally, these findings are interpreted and the possible mechanism of the antitumor effects of saffron extract are discussed. PMID- 8347279 TI - The IRE (iron regulatory element) family: structures which regulate mRNA translation or stability. AB - Iron regulatory elements (IREs) are a family of 28 nucleotide, non-coding elements which regulate the translation of ferritin mRNA (iron storage), erythroid delta-aminolevulinic acid synthase mRNA (heme synthesis) and the stability of the transferrin receptor (TfR) mRNA (iron uptake). IREs in the 5' end control translation (ribosome binding) and IREs in the 3' end control turnover (degradation). The specific regulator protein, the IRE-BP, is a member of the aconitase family but binds RNA only in the apo form without the Fe-S cluster. Cellular iron alters the IRE/IRE-BP interaction leading to translation of ferritin and eALAS mRNAs but degradation of the TfR mRNA. IRE function requires proximity to the 5' cap, achieved either by a short leader (eALAS) or a long, base-pairing flanking region (FL) (ferritin); a conserved triplet of FL base pairs enhances repression of ferritin mRNA. TfR mRNA has five AU-rich IREs which can also form an alternate structure with inter-IRE base pairs, in the absence of the IRE-BP. Ferritin IREs regulate both translation repression (negative control-IRE-BP dependent) and enhancement (positive control-initiation factor dependent); IRE-BP binding induces conformational changes in the FL. IREs use CAGUGU/C to form a hairpin loop with specific variations in the stem such as internal or bulge loops. A current structural model obtained using metallonucleases (1,10-phenanthroline-Cu, Fe-EDTA, Fe-bleomycin) and a preliminary analysis of the NMR spectrum, is a distorted helix with folds. The effect of cellular iron, Fe-S clusters and heme on the IRE-BP/RNA is not completely understood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347280 TI - Hypusine: its post-translational formation in eukaryotic initiation factor 5A and its potential role in cellular regulation. AB - The amino acid, hypusine [N epsilon-(4-amino-2-hydroxybutyl) lysine], a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology eIF-4D), is formed post-translationally in two enzymatic steps: (i) transfer of the 4-aminobutyl moiety of the polyamine spermidine to the epsilon-amino group of a single specific lysine residue in the eIF-5A precursor protein to form an intermediate, deoxyhypusine, and (ii) subsequent hydroxylation in this 4-aminobutyl portion. Hypusine is produced soon after the translation of eIF-5A mRNA; the modification is essentially irreversible. Hypusine is found in all eukaryotes examined as well as in archaebacteria; it does not occur in eubacteria. The protein containing hypusine from each species displays a high degree of amino acid identity; the sequence of amino acids surrounding the hypusine residue is strictly conserved, suggesting the importance of the hypusine modification throughout evolution. Expression of one of the two yeast eIF-5A genes is required for survival and the lysine codon at the site of hypusine synthesis is vital for yeast growth. The precise cellular function of eIF-5A remains to be elucidated; however, eIF-5A stimulates methionyl-puromycin synthesis in a model assay for translation initiation and eIF-5A precursors containing lysine in place of hypusine are inactive in this assay. This provides evidence that the hypusine modification is needed for eIF-5A activity. In view of the important role of hypusine in eIF-5A and because of the narrow specificities of the enzymes involved in formation of this unusual amino acid, the hypusine biosynthetic steps offer promising targets for intervention in cellular proliferation. Spermidine analogs that are inhibitors of deoxyhypusine synthase in vitro also cause inhibition of hypusine formation in cells, together with a reduction in protein synthesis and in cell growth. In addition, certain metal chelating inhibitors of deoxyhypusine hydroxylase exhibit anti-proliferative effects by arresting mammalian cells at the G1/S boundary of the cell cycle. These results lay the foundation for the potential regulation of cellular events through the application of specific and potent inhibitors of hypusine biosynthesis. PMID- 8347282 TI - Using pressure measurements to evaluate different technologies. AB - Despite ongoing efforts to improve the prediction, prevention, and treatment of pressure ulcers, clinicians continue to face an overwhelming array of confusing, and sometimes conflicting, information about the technologies used to lower pressure. The purpose of this article is to explain the fundamental differences among units of pressure measurement and those pressures (capillary closing, tissue interface, internal cushion, and hydrostatic) that are commonly described in research as well as sales literature. A clearer understanding of these parameters will help clinicians make informed evaluations of distinct technologies, set realistic expectations for different products, and achieve desired outcomes cost-effectively. PMID- 8347281 TI - The evaluation of five specialized support surfaces by use of a pressure sensitive mat. AB - This study used two full-size pressure-sensitive mats to evaluate five patient support surfaces. The mats, containing 1,536 and 2,340 pressure measurement sites, respectively, made it possible to quantify the entire interface pressure distribution of each support surface. Measurements for groups of 64 and 32 subjects were obtained in supine positions of 0 degree, 30 degrees, at maximal head elevations (50 degrees-60 degrees), and at lateral recumbency. Several statistical descriptors were calculated to characterize the interface pressure distributions. The support surfaces tested included: a powered-air overlay (ACUCAIR Continuous-Air-flow System), a low-airloss bed (FLEXICAIR MC3 Low Airloss Therapy), a continuous lateral-rotation low-airloss bed (RESTCUE Dynamic Air Therapy), an air-fluidized bed (CLINITRON II Air-Fluidized Therapy), and an integrated bed (prototype Advance 2000 Bed). An analysis of variance revealed that the interface pressure was significantly lower and weight-bearing area was significantly higher on the five surfaces, when compared to the standard hospital mattress. PMID- 8347283 TI - Lack of nutrition in AHCPR prevention guideline. PMID- 8347284 TI - A critique of the AHCPR's "Preventing pressure ulcers--a patient's guide" as a written instructional tool. AB - Preventing Pressure Ulcers--A patient's guide was released by the Agency for Health Care Policy and Research (AHCPR) in May 1992. Using criteria suggested by Falvo (1985), Redman (1988), Ruzicki (1989), and others, the guide was critiqued to determine how it compared to existing criteria for evaluating written tools. The AHCPR guidelines does not meet all the criteria; suggestions for improvement are provided. PMID- 8347285 TI - Exploring the validity of data-gathering instruments. AB - The validity of an instrument is another important issue for the clinician to consider when selecting a tool for use in data collection. Broadly defined, validity refers to the extent to which an instrument measures what it is supposed to be measuring. Although validity is a unitary concept, this article explores three common categories of validity: content, criterion-related, and construct validity. PMID- 8347286 TI - Kudos to Dr. Deloach for article on osteomyelitis. PMID- 8347287 TI - Collaboration produces results. PMID- 8347288 TI - Human immunodeficiency virus (HIV) infection. Does it increase susceptibility to adverse drug reactions? PMID- 8347289 TI - Oral contraceptives. Are drug interactions of clinical significance? AB - There is a large quantity of literature on drug interactions with oral contraceptive (OC) steroids although their incidence is not known. The potential clinical significance of some interactions makes it important for all prescribing doctors and dentists to have some knowledge of the topic. Interactions may be divided into those in which OC effectiveness is impaired, causing breakthrough bleeding or pregnancy, those in which OC activity is enhanced by other drugs and those in which OCs interfere with the metabolism or activity of other therapeutic agents. Consideration of their pharmacology indicates that impairment of OC effect is most likely to be due to interference with ethinylestradiol. This is because this compound is sulphated in the gut wall, hydroxylated and glucuronidated in the liver, and undergoes enterohepatic recirculation. The progestogens are only metabolised in the liver and have no significant enterohepatic recirculation. Protein binding interactions are rarely of clinical importance. OC plasma concentrations may be reduced by induction of hepatic metabolism in the case of griseofulvin, rifampicin (rifampin) and several anticonvulsant drugs; valproic acid (sodium valproate) does not have this effect. Antibiotics may interfere with enterohepatic recirculation of ethinylestradiol and reduce plasma levels of active hormone. This is probably only of significance in a subgroup of women who may sometimes be suspected on history, but cannot be identified by any diagnostic test. Reasons for differences between case reports and formal studies of interactions with antibiotics are discussed. Plasma concentrations of ethinylestradiol may be increased by ascorbic acid (vitamin C) and paracetamol (acetaminophen) which compete with it for sulphation in the gut wall. Theoretically, problems may arise if these agents are stopped suddenly. Imidazole antifungal agents can inhibit ethinylestradiol metabolism and increase its plasma concentrations but the clinical significance of this is unknown. OCs have been shown to inhibit metabolism of many therapeutic drugs and increase their plasma concentrations. This may be of clinical significance in the case of benzodiazepines which are hydroxylated in the liver, but clinical effects are less certain with the other agents. OCs may induce metabolism of other drugs which are glucuronidated, including some benzodiazepines and analgesics. The clinical significance of this type of interaction is also unknown. It is suggested that all prescribers should remember to ask about OCs when taking a drug history and to consider the possibility of interactions with other drugs. PMID- 8347290 TI - Risks and benefits of drugs used in the management of the hyperactive child. AB - Childhood hyperactivity is a common behavioural complaint. The therapeutic options for physicians caring for children with hyperactivity are considerable and varied; current recommendations call for a multidisciplinary approach, including when necessary the use of drug therapy. Central nervous system stimulants are the primary agents used in the therapy of hyperactivity. The majority of children with hyperactivity diagnosed using careful clinical criteria will demonstrate short term benefits in cognitive and behavioural terms, but long term efficacy remains controversial. There appears to be a subset of patients who do not demonstrate a beneficial response to stimulants, although there is controversy as to whether this may be dose dependent. The adverse effects of most concern are suppression of growth, the development of tics and the potential for abuse. Antidepressants and clonidine are useful agents for the therapy of patients resistant to stimulant therapy. Although the most frequent adverse events of antidepressant therapy are associated with the anticholinergic activity of these agents, the most common serious adverse events are associated with antidepressant overdose. Concern has been expressed because of case reports describing an association between antidepressant therapy for hyperactivity and sudden death. A number of other therapies have been used for hyperactivity. Although these therapies may be effective in subsets of patients with hyperactivity, there is little research detailing how to identify patients who might be expected to respond to such treatment. PMID- 8347291 TI - Epidemiology of drug-drug interactions as a cause of hospital admissions. AB - The purpose of this review was to focus on hospital admissions caused by a specific type of adverse drug reaction (ADR) that can be assumed to be avoidable in almost all cases: the drug-drug interaction (D-DI). To determine the epidemiology of D-DIs in hospital admissions, a review of the adverse drug reaction literature was undertaken to answer several questions: (a) what is the incidence of hospital admissions attributable to D-DIs?; (b) what percentage of drug-related hospital admissions are attributable to D-DIs?; (c) are there any patterns to the above findings, i.e. are some D-DIs or specific drugs more likely to have been associated with hospital admissions?; and (d) are there certain patient risk factors (e.g. age) that are associated with D-DIs that led to a hospital admission? Nine ADR studies were found that either included a D-DI category as a cause for hospital admissions, or provided sufficient information so that a causal relationship could be inferred. The incidence of hospital admissions due to D-DIs ranged from 0 to 2.8%. The data found in the studies we reviewed, however, were insufficient to allow meaningful quantification of specific drugs as usual causes for D-DI-related admissions, and because of the very small numbers of patients for which a D-DI was believed to be the cause it is not possible to provide a meaningful summary of risk factors specific for D-DI admissions. We cannot conclude that D-DIs are a significant problem. There is a need to view the quantification of D-DIs in relation to the number of medications prescribed by physicians, dispensed by pharmacists and taken by patients. PMID- 8347294 TI - Lymphocyte activation and effector functions. Editorial overview. The role of cell surface molecules. PMID- 8347295 TI - Transmembrane signalling through the T-cell-receptor-CD3 complex. AB - Recent data support the existence of activation motifs within different subunits of the T-cell-receptor-CD3 complex. This architecture generates a receptor composed of discrete modules, each capable of being coupled to an effector pathway. Although new T-cell specific protein tyrosine kinases have recently been identified, the nature of the proximal non-receptor protein tyrosine kinase linking the T-cell receptor complex to essential signalling effectors remains unknown. Developmentally regulated differences in T-cell-receptor-CD3 assembly or stability may lead to the expression of isoforms displaying different sets of activation motifs. Whether this may be the basis of differential signalling during T-cell development is still a matter of speculation. PMID- 8347293 TI - Inhaled corticosteroids in children. Is there a 'safe' dosage? AB - Inhaled corticosteroids are effective for the treatment of asthma. Because of the appreciation of the importance of airway inflammation in the pathogenesis of the disease, these drugs are being used more frequently not only in severe but also in moderate asthma. Treatment rarely has to be stopped because of topical adverse effects since oropharyngeal candidiasis and dysphonia are uncommon in children. However, paediatricians need to remain alert for the possibility of systemic adverse effects. With sensitive techniques, dose-dependent adrenal suppression has been documented in children treated with inhaled steroids but generally this effect has no clinical relevance. Although suppression of short term growth velocity has been reported, long term studies have shown that when growth impairment occurs in a child with asthma it is more likely to reflect poor asthma control than the administration of inhaled corticosteroids. Calcium supplementation may be necessary in children with asthma treated with inhaled steroids since this treatment may cause reduction in osteocalcin, a marker of osteoblast activity and bone formation. Other systemic adverse effects have been reported in case reports. The use of a large spacer device has been shown to reduce the incidence of both topical and systemic adverse effects from inhaled steroids and their use should be encouraged. In any child with asthma who really needs inhaled steroids, the lowest dose possible should be prescribed; however, the mistake of prescribing doses too low to be therapeutically effective should be avoided. PMID- 8347297 TI - The tyrosine kinase connection: how GPI-anchored proteins activate T cells. AB - How can crosslinking of cell-surface glycosylphosphatidylinositol-anchored proteins activate T cells when the proteins do not reach the cytosol? Recent results show that glycosylphosphatidylinositol-anchored proteins associate with tyrosine kinases of the src family. Kinase activity is stimulated when glycosylphosphatidylinositol-anchored proteins are crosslinked. How the proteins are linked across the membrane, however, remains an intriguing mystery. PMID- 8347296 TI - CD4, CD8 and the role of CD45 in T-cell activation. AB - CD4, CD8 and CD45 regulate the coupling of the T-cell receptor complex (CD3-TCR) to tyrosine kinase activation and phosphorylation of key substrates such as phospholipase C gamma 1. CD4 and CD8 contribute to activation signals through their cytoplasmic association with p56lck. Expression of the zeta-chain is required for functional synergy of the T-cell receptor with CD4 in the activation of phospholipase C gamma 1, which probably reflects an interaction between p56lck and zeta-associated kinase ZAP-70. CD45 expression is required for CD3-TCR signaling. CD45 may positively regulate signaling by dephosphorylating the carboxyl-terminal tyrosine of p56lck and p59fyn, and negatively regulate signaling by dephosphorylation of other TCR-associated substrates directly. One ligand for CD45 receptor has been identified as the B cell CD22 molecule. The positive and negative effects of CD45 are sensitive to the composition of CD45 in receptor complexes, and may be regulated by specific associations of CD45 isoforms with other receptors such as CD3-TCR, CD2 and CD4. PMID- 8347299 TI - Antigen-presenting cell types. AB - Different antigen-presenting cells elicit responses in different T-cell populations for primary activation, secondary stimulation and cytotoxic effector functions. Maturing bone marrow derived dendritic cells may acquire and process antigens, transport them to lymph nodes and activate naive T cells located there. By contrast, follicular dendritic cells, acquiring antigen-antibody complexes, maintain 'memory' via B-cell activation. Effector memory T cells recognize various tissue cells bearing antigen and we speculate that they may also target specialized antigen-presenting dendritic populations. PMID- 8347298 TI - Regulation of B-cell activation and antigen presentation by Fc receptors. AB - Fc receptors are a family of membrane-associated and soluble glycoproteins that mediate a vast array of functions triggered by immune complexes. The structures of murine and human Fc gamma and Fc epsilon receptors have been elucidated and the motifs involved in the activities that they mediate characterized during the past year. B-cell activation and differentiation may be enhanced by different Fc receptor isoforms either through an increased presentation of antigen associated with IgG (Fc gamma RIIb2, Fc gamma RIII, Fc epsilon RII), or the induction of cytokine synthesis by mast cells (Fc epsilon RI, Fc gamma RIII) and natural killer cells (Fc gamma RIII). Conversely, the crosslinking of Fc gamma RIIb1 to membrane Ig inhibits B-cell activation. Soluble forms of Fc receptor also regulate antibody production by enhancing interleukin-4-induced IgE synthesis (Fc epsilon RII) or inhibiting IgG synthesis (Fc gamma R). Different structural motifs are responsible for the different biological activities of each Fc receptor isoform. PMID- 8347292 TI - Genetically determined adverse drug reactions involving metabolism. AB - Genetic factors represent an important source of interindividual variation in drug response. Relatively few adverse drug effects with a pharmacodynamic basis are known, and most of the well characterised inherited traits take the form of genetic polymorphisms of drug metabolism. Monogenic control of N-acetylation, S methylation and cytochrome P450-catalysed oxidation of drugs can have important clinical consequences. Individuals who inherit an impaired ability to perform one or more of these reactions may be at an increased risk of concentration-related toxicity. There is a strong case for phenotyping before starting treatment with a small number of drugs that are polymorphically N-acetylated or S-methylated. However, the issue of clinical significance is perhaps most relevant for the debrisoquine oxidation polymorphism, which is mediated by cytochrome CYP2D6 and which determines the pharmacokinetics of many commonly used drugs. Phenotypic poor metabolisers of debrisoquine (8% of Caucasian populations) taking standard doses of some tricyclic antidepressants, neuroleptics or antiarrhythmic drugs may be particularly prone to adverse reactions. Similarly, clinically relevant drug interactions between these drugs and other substrates of cytochrome CYP2D6 may occur in the majority of the population who are extensive metabolisers. However, it is clear that in the majority of cases there is a need for controlled prospective studies to determine clinical significance. Accordingly, routine debrisoquine phenotyping or genotyping before beginning drug treatment is difficult to justify at present, although it may be helpful in individual cases. When prescribing drugs whose metabolism is polymorphic alone or in combination, careful titration of the dose in both phenotypic groups is prudent. In some cases it will be preferable to use alternative therapy to avoid the risk of adverse drug reactions. PMID- 8347300 TI - T cell mediated immunosuppression. AB - Suppressor T cells down-regulate the activity of other cells in the immune system, and, albeit controversial, are believed to play a role in immunological tolerance and immunoregulation. Significant progress has been made in characterizing suppressor T cells and their receptors, and in elucidating mechanisms of immunosuppression. This knowledge is important for understanding the immune system and certain disease states and for favorably manipulating immunity. PMID- 8347301 TI - Sites of B-cell activation in vivo. AB - Novel techniques have made possible in situ analyses of the lymphocyte populations responding to antigen. In the spleen, antigen-specific T and B cells are first observed in the periarteriolar lymphoid sheath. Following conjugate formation between specific T and B lymphocytes, B-cell proliferation and differentiation takes place in two distinct sites, the periarteriolar lymphoid sheath-associated foci and germinal centers. PMID- 8347302 TI - Homing of naive, memory and effector lymphocytes. AB - Lymphocyte subsets home in a particular manner depending on their class, state of activation and 'allegiance' to certain tissues. Naive lymphocytes home preferentially through lymphoid tissues, whereas effector and memory cells home preferentially through non-lymphoid tissues and exist as phenotypically distinct subsets with preferential localization to gut, skin or other tissues. These migration pathways, which correlate with different functional properties of lymphocyte subsets, increase the efficiency of the immune system. PMID- 8347303 TI - Immune privilege as the result of local tissue barriers and immunosuppressive microenvironments. AB - As the cellular and molecular bases of immune privilege are elucidated experimentally, the phenomenon emerges as an active and dynamic exercise in immune regulation. Local tissue factors play a key role in the establishment and maintenance of privilege, particularly tissue cytokines and mediators within the local microenvironment, which modify both the induction and expression of immunity to antigens that are introduced into, or arise within, privileged sites. PMID- 8347305 TI - Lymphocyte activation and effector functions. PMID- 8347304 TI - Lifespans of naive, memory and effector lymphocytes. AB - Typical T and B lymphocytes in the secondary lymphoid organs are long-lived cells that are selected from a large pool of short-lived precursor cells in the primary lymphoid organs. The bulk of mature T and B cells are immunologically naive and remain in interphase for prolonged periods. Contact with specific antigen causes these naive cells to proliferate rapidly and differentiate into a mixture of short-lived effector cells and long-lived memory cells. Memory cells have a rapid turnover, and the survival of these cells appears to require persistent contact with antigen. PMID- 8347306 TI - 7-Chloromethyl-12-methylbenz(a)anthracene. AB - C20H15Cl, M(r) = 290.8, monoclinic, P2(1)/c, a = 20.449 (4), b = 11.473 (2), c = 13.025 (2) A, beta = 108.91 (1)degree, V = 2890.9 A, Z = 8, Dx = 1.336 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 21.14 cm-1, F(000) = 1216, T = 294 K, R = 0.045, wR = 0.049, for 3471 diffractometer data [Io > or = 3 sigma (I)]. The ring system is puckered as a result of the bulkiness of the 12-methyl group. PMID- 8347307 TI - 3-[1-(Ethylamino)ethylidene]-6-methyl-3H-pyran-2,4-dione. AB - The structural results clearly indicate that 3-[1-(ethylamino)ethylidene]-6 methyl-3H-pyran-2,4-dione exists as a keto-enamine tautomer in the solid state. The H atom bonded to N(9) refines with a normal temperature factor and the bond distance of the keto group [C(4)--O(13)] of 1.263 (1) A is elongated due to resonance. This resonance is also indicated by an averaging of the single bonds [C(2)--C(3), C(3)--C(4), C(4)--C(5) and C(8)--N(9)] and double bonds [C(3)--C(8) and C(4)--O(13)] in the crystal structure and by the fact that not only is the pyran ring planar [r.m.s. deviation 0.0212 (9) A] but also there is planarity for the whole molecule [r.m.s. deviation 0.074 (1) A]. A strong intramolecular hydrogen bond is found between the 4-oxo group and the amine H atom. PMID- 8347308 TI - Deconvolution of disoriented fiber diffraction data using iterative convolution and local regression. AB - Computationally efficient procedures are described for the deconvolution of disoriented fiber diffraction data to the resolution limit of measurable intensity in the patterns. The methods can be applied to diffraction data from imperfectly parallel arrays of one-dimensionally periodic rods or two dimensionally periodic sheets, randomly rotated about their unique axes, to derive a representation of the intensity distribution corresponding to perfectly parallel orientation. With use of angular convolution and local angular regression, a set of uniform cylindrically averaged squared structure factors are iteratively adjusted, subject to a minimum-wavelength constraint, until they produce a disoriented pattern that fits the observed diffraction data. The results from this deconvolution provide a measure of the properly scaled cylindrically averaged squared structure factors, which can be used with other structural information to construct a physically plausible trial model suitable for further refinement. Sample deconvolutions of simulated X-ray patterns from partially oriented gap junction membranes are presented and the results from point-model deconvolutions are compared to those from constrained deconvolutions that began with the transform of a physically plausible trial model. PMID- 8347309 TI - Frequency statistical method for evaluating cosine invariants of three-phase relationships. AB - A new variation on the established procedure to evaluate three-phase structure invariants through quadrupole relationships is described. This method differs from earlier algebraic formulations in that the cosine-invariant estimates are based on a conditional observed frequency distribution of magnitude of E magnitudes for the quadrupole, rather than on the values of the magnitudes themselves. Successful applications of this method to a number of structures that ranged in size from 84 to 317 independent non-hydrogen light atoms are given. PMID- 8347311 TI - Determinants and consequences of the diurnal rhythm of blood pressure. AB - The diurnal rhythm of blood pressure (BP) is influenced by both extrinsic and intrinsic factors, with the former usually being of greater significance. Non dippers, in whom the normal nocturnal fall of pressure is diminished, have been reported to show more target organ damage (left ventricular hypertrophy (LVH)) than dippers, which may be explained by a higher average 24 h BP. Whether or not the pattern of BP (as opposed to the level) also is prognostically important is probable but unproven, given the known morning surge of the incidence of many acute cardiovascular events. The pathological significance of different diurnal patterns of BP change may depend both on the method of analysis and on the outcome measure used. PMID- 8347310 TI - Ambulatory blood pressure. A personal historical account. PMID- 8347312 TI - The influence of behavioral factors on the daily variation of blood pressure. AB - Blood pressure (BP) changes continually throughout the day and night in response to changes in activity and in the environment. Behavioral influences include posture, physical and mental activity, and emotional state. The absolute magnitude of these influences may show consistent differences according to demographic factors such as gender and environment (eg, at work or at home). Occupational stress appears to have a greater effect on the BP in men than in women, while domestic stress (eg, the number of children) influences BP more in women. Ambulatory BP recordings should be interpreted according to the behavioral setting in which they are made. PMID- 8347313 TI - Can simultaneous ambulatory blood pressure and activity monitoring improve the definition of blood pressure? AB - In this study we measured activity and sleep time, using a wrist actigraph, in a population of 319 patients referred for ambulatory blood pressure monitoring (ABPM). Mean waking and sleeping blood pressure (BP) and the diurnal BP variation derived with this technique were compared to daytime (defined variously as 7 AM to 8 PM, 7 AM to 10 PM, or 7 AM to midnight) and nighttime pressure. To study the relationship of actigraph-derived activity data to BP variability in more detail, 30 patients underwent paired monitoring 1 to 18 (mean 8) days apart. Mean waking BP was then corrected for activity to determine whether this technique could improve reproducibility. Statistically but not clinically significant differences between waking and daytime BP were seen, with larger and potentially clinically relevant differences between sleeping and nighttime BP. The midnight to 7 AM time period gave the best estimate of observed sleeping time and the nocturnal dip of BP. The average correlation between activity and BP was 0.25 for systolic and 0.34 for diastolic BP, but with wide variation in the strength of the relationship both between and within individual patients. On average, activity accounts for 20% of systolic and 26% of diastolic BP variation. Correcting the mean waking BP to a standard activity level reduced within-patient variation by 6%/9%. This made no significant difference to overall reproducibility, perhaps because variability in this sample was low before adjustment, with the standard deviation of the difference equal to 8/4 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347315 TI - Fourier analysis of blood pressure profiles. AB - This short review deals with the use of the Fourier technique to analyze diurnal blood pressure (BP) profiles obtained by noninvasive ambulatory monitoring. A Fourier series with four harmonics strikes an acceptable balance between the accuracy and complexity required to model the diurnal profile accurately in most subjects. A weighting procedure makes it possible to allow for the varying time intervals between consecutive pressure readings. Studies based on a single recording are insufficient to characterize an individual with respect to the statistical parameters describing the diurnal BP profile, regardless of whether they are obtained by Fourier analysis or by other methods. The Fourier approach provides the means to translate 24 h BP profiles into interpretable statistical parameters, such as the amplitude and acrophase of the overall model and the harmonics. These parameters can subsequently be used in further statistical analyses. In conclusion, the Fourier approach makes the description of complex, asymmetrical, and multiphasic BP profiles possible. By using the procedures of linear multiple regression, commonly provided by software packages, the calculations can be readily implemented on microcomputers without requiring advanced skills in mathematics or programming techniques. PMID- 8347316 TI - Spectral analysis of 24 h blood pressure recordings. AB - Spectral analysis of blood pressure and heart rate signals allows overall blood pressure and heart rate variabilities to be split into their different frequency components. When used to analyze 24 h discontinuous blood pressure recordings, the low sampling frequency that characterizes these devices allows only the slow fluctuations in day and night blood pressure to be adequately described by the spectral approach. Conversely, spectral analysis of continuous blood pressure recordings provides information both on fast and slow changes in blood pressure and heart rate. Because blood pressure and heart rate powers are characterized by a 1/f distribution over the 24 h, slow fluctuations in blood pressure and heart rate contribute most importantly to 24 h variance, while faster components provide only a minor contribution. However, spectral analysis of the latter has raised considerable interest due to the possible association of these components with cardiovascular regulatory mechanisms. It is now possible to perform 24 h dynamic spectral analysis of blood pressure and heart rate on continuous blood pressure recordings obtained noninvasively by a finger pressure device. PMID- 8347314 TI - Age-specific characteristics of nocturnal blood pressure in a general population in a community of northern Japan. AB - The age- and gender-specific profile of circadian blood pressure variation was examined by monitoring ambulatory blood pressure (ABP) in 477 untreated subjects in a rural community of northern Japan. Autoregressive spectral analysis demonstrated three major peaks at around 24, 12, and 8 h. We fitted a truncated Fourier series with three harmonics to the blood pressure (BP) data using least squares regression. More than half of the BP and pulse rate periodic curves were bimodal, one-third were trimodal, and the remainder were unimodal. The nadir of BP appeared between 00:00 and 01:30, and that of pulse rate occurred between 00:30 and 02:00. The nadir of systolic and diastolic BP, as well as pulse rate, appeared earlier with increasing age, and the difference between subjects in their 20s and those in their 70s was about 1 h. The amplitude of 24 h BP decreased with increasing age in men, but not in women. This type of information on the circadian BP profile of a general population is useful for the diagnosis and treatment of hypertension. PMID- 8347318 TI - Analysis of blood pressure variability. PMID- 8347317 TI - The clinical utility of blood pressure load in hypertension. AB - The variability of blood pressure and its consequences suggests that ambulatory blood pressure (ABP) data should be analyzed not only by mean ambulatory blood pressure (MABP), but also by looking at blood pressure load (BPL, the percentage of measurements > 140/90 mm Hg while awake and > 120/80 while asleep). In one study, several hypertensive patients whose ambulatory diastolic blood pressure was < 90 mm Hg had a diastolic load near 50%. Studies have reported strong correlations between BPL and indices of target-organ changes such as left ventricular mass index (LVMI). It was necessary to lower office blood pressure to < 85 mm Hg to reduce BPL to a normal range of 15 to 20%. To further investigate the usefulness of BPL in the study of hypertension, more longitudinal studies of cardiovascular disease and blood pressure variability are needed. PMID- 8347319 TI - Defining normal ambulatory blood pressure. AB - Providing normal reference values and the means to interpret such values in practice is an urgent issue requiring consensus. Five basic approaches to defining normalcy for 24 h blood pressures (BP) are considered: 1) the relationship of ambulatory blood pressure (ABP) to morbidity and mortality, 2) the relationship of ABP to end-organ involvement, 3) ABP levels in normal populations, 4) the relationship of ABP to clinic BP, and 5) the relationship of 24 h indices to risk. Although there now is considerable evidence demonstrating that ambulatory measurement correlates more strongly with end-organ damage, the first two approaches are scientifically the best. It will be some time before levels of normalcy can be derived. There is a large volume of data on population samples permitting derivation of normalcy for clinical practice. Rounded upper limits of normal can be calculated as 140/90 mm Hg for 24 h ambulatory pressure, 150/90 mm Hg for daytime pressure, and 130/80 mm Hg for nighttime pressure. There are, however, considerable differences for age and gender which need to be taken into consideration. PMID- 8347321 TI - What is normal blood pressure? Comparison of ambulatory pressure level and variability in patients with normal or abnormal left ventricular geometry. AB - To assess the level and pattern of normal ambulatory blood pressure (ABP) using a non-BP standard to identify normality, we examined the level and variability of ABP during the waking day, at work, at home, and during sleep and looked at physician and technician BP measurements in 191 adults whose left ventricular (LV) geometry was classified by echocardiography. Clinic BPs were similar in the 120 subjects with normal LV geometry and the 35 subjects with concentric LV remodeling. Pressures were only modestly higher in the 15 subjects with concentric LV hypertrophy than in the 21 with eccentric hypertrophy. In contrast, these subject groups differed with regard to their ABPs during the waking hours, at home, and especially at work. However, no difference in BP variability, as assessed by the standard deviation of awake systolic or diastolic BP, existed among the subject groups identified by LV geometric patterns. Comparison of patients with concentric LV hypertrophy, the LV pattern associated with the worst prognosis, with normotensive subjects with normal LV geometry suggests that awake ABPs in adults below 139/86 mm Hg might be considered normal, whereas values over 149/95 mm Hg might be considered pathologic. Verification of these conclusions is needed, however, in larger series and with the use of additional measures of preclinical hypertensive disease. PMID- 8347320 TI - Defining normal ambulatory blood pressure in relation to target organ damage and prognosis. AB - It is premature to state that ambulatory blood pressure (ABP) values below a given level should be considered normal, and those above it abnormal, in terms of prognostic implications on cardiovascular (CV) morbidity. We do not know whether CV morbidity in hypertensive subjects with apparently normal ABP (white coat hypertension) is less than that in patients with higher ABP levels and similar to that of healthy normotensive subjects, or whether the effects of antihypertensive drug treatment on CV morbidity are superior to placebo in white coat hypertension. It is important to achieve agreement on a temporary working definition of normal ABP to be used to test two main hypotheses: 1) in subjects with white coat hypertension, CV morbidity is less than that in patients with higher ABP levels; and 2) drug treatment is not superior to placebo in reducing CV morbidity in white coat hypertension. Normal ABP values can be derived empirically from population based samples, in selected groups of healthy subjects, or from meta-analyses. However, the significance of the definition of a normal ABP range is the identification of clinically hypertensive patients at low risk of future CV morbid events. Using echocardiographic left ventricular (LV) mass as a surrogate outcome measure, we found that the coexistence of mean daytime ABP levels < 134 mm Hg systolic and < 90 mm Hg diastolic, regardless of gender (< 136/87 mm Hg in men and 131/86 mm Hg in women) identifies a subgroup of clinically hypertensive subjects with echocardiographic LV mass, and associated prevalence of left ventricular hypertrophy (LVH) similar to those found in healthy normotensive control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347322 TI - Ambulatory blood pressure monitoring. Can a clinical role be defined? AB - Automated ambulatory blood pressure monitoring (ABPM) is a powerful research tool, but its clinical role has been difficult to define. This paper presents conclusions on the potential clinical benefits, risks, and costs of ABPM based on a comprehensive review of the scientific literature. Support is strongest for the uses of ABPM to improve blood pressure (BP) classification in suspected hypertensives and in patients with apparent drug resistance. Four policy options are discussed. Approval for limited clinical applications appears warranted provided it is accompanied by 1) quality control standards for ABPM laboratories, 2) decision thresholds for equating office, self-monitored, and ABPM BP levels, and 3) steps to limit profit incentives and the high risk of overutilization. PMID- 8347323 TI - Ambulatory blood pressure monitoring can improve cost-effective management of hypertension. AB - Detection and treatment of arterial hypertension is effective, as shown by clinical trials and downward trends in cardiovascular disease. This process causes expenditures that progressively have increased because of inclusion of more patients with minimally elevated pressure who incur a higher cost of treatment. Average daily pressure is a more accurate predictor of outcome and morbidity than initial screening or occasional clinic monitoring of pressure. Noninvasive ambulatory blood pressure monitoring (ABPM), as a secondary screening, reveals that 20% to 60% of those initially labeled as hypertensive have average daily pressures low enough to delay the initiation of drug therapy. These observations permit the development of forecasting models comparing strategies for management of hypertension. Preliminary estimates show that use of ABPM might reduce the number of patients requiring drug treatment over a 6 year period, with reduced cumulative and yearly costs for this interval. Forecasting models using ABPM now should be tested in comprehensive health care systems to determine their effect on overall cost-effectiveness in the management of hypertension. PMID- 8347324 TI - Clinical usefulness of ambulatory blood pressure monitoring. AB - During the last decade, ambulatory blood pressure monitoring (ABPM) made a transition from a method reserved for clinical investigators to a technique considered useful by practicing physicians in assessing certain problems in hypertension. Recent recommendations of the National High Blood Pressure Education Program (NHBPEP) Working Group on Ambulatory Blood Pressure Monitoring suggested using ABPM for a number of clinical problems, including borderline hypertension without target organ damage, evaluation of drug resistance, and white-coat hypertension. We evaluated the clinical indications for ordering ABPM by Connecticut physicians both in hospital and community-based practices. Through specific questionnaires, the clinical indications used by referring physicians to order ABPM and their inclinations for future use of the methodology were assessed. Forty-seven of 70 physicians (65%) responded to the questionnaire, basing their answers on 237 patients. The majority of physicians were internists (57%) or cardiologists (25%). Leading indications for patient referral for ABPM included borderline hypertension (27%), assessment of drug therapy/BP control (25%), and possible white-coat hypertension (22%). Far fewer referrals were observed for severe hypertension or as a routine test for the diagnosis of hypertension. These data suggest that practicing physicians have become aware of the usefulness of ambulatory blood pressure recordings and are following the NHBPEP guidelines on referral for the study. PMID- 8347325 TI - Reproducibility of ambulatory blood pressure and assessing treatment withdrawal in hypertension trial. AB - Ambulatory blood pressure monitoring (ABPM), like casual blood pressure (BP), is imperfectly reproducible between visits. The reproducibility of ABPM is less than the reproducibility predicted from a simple model of random variation of BP. This suggests either increased technical error in the technique, an element of increased biologic variability, or both. In addition, ABP shows a between-day variation (add about 6 to 7 mm Hg diastolic, similar in magnitude to what is observed with casual BP) which cannot be obviated by the average of many within day measurements. The reliability of ABPM, although conventionally judged excellent at about RI = 0.75, is insufficient to avoid misclassification errors and regression to the mean when BP cutpoints are employed. About 40% of patients apparently failing treatment withdrawal at a threshold of +2 SD, or about 95 mm Hg diastolic ABP, will be false-positive failures when categorized by a single ABP. Despite the inconvenience, obtaining an average of two or more ABP measurements on different days may be cost-saving to a clinical trial because of the improved reproducibility; other costs may exceed $1000 per entrant. PMID- 8347326 TI - Ambulatory blood pressure monitoring in the design of studies on antihypertensive drug efficacy. AB - Ambulatory blood pressure monitoring (ABPM) provides advantages for studies of the efficacy of antihypertensive drugs in addition to demonstrating antihypertensive effects in daily life conditions. For example, ABPM is devoid of the "white coat" effect and can thus more precisely estimate the relative proportion of responders and nonresponders to treatment. It also may reduce the study size because of the greater reproducibility of 24 h average blood pressure (BP) (as compared to clinic BP) and the lack of a substantial placebo effect, which eliminates the need for a placebo group. Some disadvantages exist, including the inability of automatic ABPM to consistently provide accurate BP readings and to estimate BP variability. Finally, hourly average BPs are less reproducible than their average 24 h counterpart, which may make it more difficult to statistically demonstrate an antihypertensive effect throughout the 24 h. Some of these disadvantages, however, may be reduced in the near future by new ABPM devices. PMID- 8347327 TI - Ambulatory blood pressure monitoring. A critique on clinical issues and clinical trials. PMID- 8347328 TI - A pilot clinical trial of the angiotensin-converting enzyme inhibitor ceranapril in Alzheimer disease. AB - This pilot clinical trial was a 15-week, double-blind, controlled, three-way crossover study evaluating cognitive effects of ceranapril in subjects with dementia of the Alzheimer type (age range 50-75 years). Computerized (CNTB) and noncomputerized cognitive test batteries revealed no significant results (p > 0.05). On further analysis of the data, however, a study of longer duration and/or higher dosages may be warranted. PMID- 8347329 TI - Alzheimer disease and physician-assisted suicide. PMID- 8347330 TI - Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson's and distinction from Alzheimer disease. AB - Senile dementia of Lewy body type or Lewy body dementia (LBD), characterized neuropathologically by the presence of Lewy bodies in the brainstem and cortex, and in most cases neocortical senile plaques (but few or no tangles), bears a closer resemblance to Parkinson's (PD) than to Alzheimer disease (AD) in its cholinergic neurochemical pathology. Thus, reductions in the biochemical activity of choline acetyltransferase were generally more extensive in neo- as opposed to archicortical regions in LBD (especially hallucinating cases) and in PD, whereas muscarinic receptor binding was significantly increased in LBD and PD but not in AD. Nerve growth factor receptor (P75) assessed immunocytochemically in the archicortex were decreased in PD and, to a lesser extent, in LBD in conjunction with reductions of neuronal numbers in the nucleus of Meynert (Ch4), but were relatively spared in AD. These observations indicate that although AD is primarily associated with dysfunction of cholinergic axonal input to the cortex, LBD and PD are more likely to involve degeneration of the basal forebrain cholinergic system. Relevance of the findings in terms of aetiopathology and cholinergic treatment strategies is discussed. PMID- 8347331 TI - Autopsy in dementing illness: who participates? AB - The frequency of occurrence of various types of dementing disorders has been ascertained primarily from autopsied series. Since autopsy is voluntary, it is unknown if these series are representative of the entire demented population. To assess this issue, all deaths occurring over a 5-year period in our Memory Disorders Clinic were reviewed, and clinical variables and diagnoses were compared between patients who were autopsied and those who were not. Sixty-nine patients died; 43% (n = 30) underwent autopsy, and 57% (n = 39) did not. Race (no black patients were autopsied), age of disease onset, age of presentation to the clinic, age of death, and interval between last clinic contact and death (significantly less for nonautopsied patients) were found to differ between the two groups. However, clinical diagnosis of dementia was similar in the two groups. The clinical diagnosis was confirmed in 84% of autopsied patients. These results suggest that there are no major differences between clinical diagnoses for autopsied and non-autopsied patients and that the frequency of occurrence of various dementias obtained through autopsied series are representative of the demented population. PMID- 8347332 TI - Lack of detectable radiation hypersensitivity in lymphoblastoid cells from multiple pedigrees of familial Alzheimer disease. AB - Recent reports suggest that cultivated nonneuronal cells from individuals with Alzheimer disease (AD) and other specific hereditary neurodegenerative disorders show hypersensitivity to DNA-damaging agents such as x-rays and radiomimetic chemicals. The hypothesis proposed is that a number of chronic neurologic degenerations, including AD, may be the result of accumulation of damaged DNA, resulting from a defect in DNA repair. We investigated this hypothesis by evaluating cells from individuals from pedigrees of familial Alzheimer disease (FAD) for hypersensitivity to x-irradiation. Sensitivity was assayed by viability measured by trypan blue dye exclusion and micronucleus formation. We tested B lymphoblastoid cell lines from nine patients and nine unaffected family members from pedigrees with FAD, three unrelated controls, three ataxia telangiectasia (AT) patients, and three Down syndrome individuals. The AT cell lines showed the expected reduced viability and increased micronucleus formation after x-ray treatment. The FAD and control lines showed marked heterogeneity with both assays. There was no significant differences between the FAD patients and controls. The wide variability in the response of cell lines from controls and patients indicates the need for more sensitive assays for detection of radiation sensitivity in cells from various neurologic disorders. PMID- 8347333 TI - A pilot study of oral physostigmine plus yohimbine in patients with Alzheimer disease. AB - Effective symptomatic treatment of Alzheimer's disease (AD) may require a combination of agents that augment cholinergic as well as noradrenergic neurotransmission. We conducted a pilot study of physostigmine plus oral yohimbine challenge in AD. Ten patients were enrolled in a 12-day double-blind protocol. Each patient received placebo q2h while awake for 5 days, followed by physostigmine 2 mg q2h while awake for 7 days. During each of these drug conditions, yohimbine challenges were administered at oral doses of 10 and 20 mg in a placebo-controlled manner. There was no significant improvement in Alzheimer's Disease Assessment Scale test performance for six patients for whom complete cognitive data were obtained for the 6 challenge days. Nine patients tolerated the protocol with no clinically significant changes in blood pressure, pulse, or electrocardiogram (ECG), and no cardiovascular, gastrointestinal, or autonomic toxicity. One patient complained of chest discomfort associated with tachycardia, a modest rise in blood pressure, and had t-wave inversion in a single precordial lead. These signs and symptoms resolved within a few hours. Serial ECG tracings and cardiac enzymes revealed no evidence of myocardial injury. This pilot study did not reveal major cognitive improvement with this regimen, but underscores the importance of careful cardiovascular monitoring during future combined cholinergic-noradrenergic therapies in AD. PMID- 8347334 TI - Magnetic resonance imaging of the spine in bone dysplasias and related disorders. AB - This article discusses the role of magnetic resonance imaging in orthopedic and neurosurgical complications of the spine in developmental disease of bone. The importance of a basic knowledge of spinal deformities in dysplasias and related disorders is stressed, and on the basis of a simple classification, a differential diagnostic list for each category is presented and illustrated with some common disorders. PMID- 8347335 TI - Congenital malformations of the spine. AB - The radiology of the congenital malformations of the spine has undergone significant advancement with the advent of newer modalities including computed tomography and, in particular, magnetic resonance imaging. Correlation with etiology and pathologic findings has improved. Congenital malformations have been classified according to neurulation and disjunction failures (dorsal) and those with persistent neurenteric connections with notochordal splitting (ventral). The most important benefit of the current state of imaging is the accurate morphologic representation of the malformation provided for the surgeon. PMID- 8347336 TI - Metabolic and degenerative diseases of childhood. AB - The metabolic and degenerative diseases of childhood are a diverse group of disorders with varied imaging features. Some of the disease processes have characteristic findings and some have no findings at all, but most present with nonspecific abnormalities in white matter. These patchy lesions, seen best on magnetic resonance scanning with T2 weighting, require a good history and a dialogue with the referring physicians to help in narrowing the differential possibilities. The major disease processes involving white matter are the dysmyelinating diseases, in which the abnormal white matter is the result of an inherited enzyme deficiency, and the demyelinating diseases, in which an acquired process such as infection destroys white matter. Several diseases result in gray matter abnormalities, including central pontine myelinolysis, MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like symptoms), Batten's disease, Leigh disease, and Wilson's disease. PMID- 8347337 TI - Magnetic resonance imaging of normal and abnormal brain development. AB - Magnetic resonance imaging (MRI) improves our ability to assess brain development and to detect anomalies of brain formation. MRI allows the assessment of brain development by analysis of the effects of myelination on the T1 and T2 relaxation times of the pediatric brain. This article discusses specific imaging strategies and the normal progression of signal intensity changes. Familiarity with this evolution of signal changes allows an estimation of the approximate stage of brain development. High-resolution multiplanar MRI provides good anatomic detail, with excellent distinction between gray and white matter. This technique allows improved detection of many classes of abnormalities of brain formation, some of which were previously detectable only at autopsy. These malformations and their imaging characteristics are discussed under the headings of: corpus callosal dysgenesis, intracranial lipomas, holoprosencephalies, septooptic dysplasia, the cephaloceles, the Chiari malformations, the Dandy-Walker complex, the cerebellar anomalies including Joubert's syndrome, and rhombencephalosynapsis, and the spectrum of neuronal migration anomalies. PMID- 8347338 TI - Intracranial infection in children. AB - This article discusses the neuroradiologic characteristics of central nervous system infections in children. These disorders are divided into two groups: those of congenital infections and those of infections in the infant and child. Congenital infections are referred to by the acronym TORCH. Inflammatory diseases in the infant and child encompass meningitis, cerebritis, and encephalitis. The heterogeneous etiologies often can be suggested by the neuroradiologic findings, as demonstrated with computed tomography and magnetic resonance imaging. This article also addresses the sequelae of destructive brain injuries. PMID- 8347339 TI - Neuroradiologic evaluation of pediatric craniocerebral trauma. AB - Although cranial computed tomography (CT) remains the initial diagnostic test in the evaluation and triage of the pediatric head-injury patient, magnetic resonance imagining (MRI) has become the next step in the diagnostic evaluation of those with focal or diffuse neurologic deficits. MRI is better able to demonstrate the extent and location of both hemorrhagic and nonhemorrhagic injury, thereby providing prognostic information. In nonaccidental head injury, MRI has proved valuable in detecting subtle subacute contusions and even not so subtle chronic subdural hematomas that may be difficult to see on CT or that can mimic enlargement of the subarachnoid space on CT. PMID- 8347340 TI - Magnetic resonance imaging of pediatric brain tumors. AB - When done with care, the visualization of brain tumors in children in most cases is easy. The challenge is in ability to predict tumor type and grade. Slightly less than half of pediatric brain tumors are in the posterior fossa. Astrocytomas, medulloblastomas, and ependymomas account for 95% of these tumors. Except for the large cysts and uniformly low T1 signal of pilocytic cerebellar astrocytomas, location and size are more important than specific imaging characteristics in predicting tumor type. Supratentorial tumors are even more variable in magnetic resonance imaging characteristics, and it is difficult to tell benign from malignant tumor in many cases. Although gadolinium enhancement is useful in defining tumor borders, it is not a completely reliable indicator of malignancy. As in the posterior fossa, location is important in deciding which type of tumor is more likely. Suprasellar tumors are usually craniopharyngiomas. Small temporal lobe tumors are often oligodendrogliomas or gangliogliomas. Astrocytomas are the most common tumor, and also variable, although most benign astrocytomas are near the midline. PMID- 8347341 TI - Pediatric spinal neoplasms. AB - Magnetic resonance imaging (MRI) is an accurate and noninvasive tool in the evaluation of children with spinal neoplasm. Localization and definition of site and extent of disease for treatment planning, the most important goals of neuroimaging in spinal neoplastic disease, have become more precise with MRI, because all spinal compartments can be seen without the need for subarachnoid puncture. Epidural and contiguous soft tissue disease, and associated vertebral abnormalities such as marrow replacement by metastatic processes, are readily confirmed during the same examination. In children, as in adults, gadolinium diethylenetriaminepentaacetic acid aids in separating intramedullary neoplasms from associated edema or syrinx, and is essential in the evaluation of intradural extramedullary spread of neoplasm. MRI is also useful in the exclusion of compressive lesions in children with systemic neoplasms and cord infarction or treatment-related transverse myelopathy. PMID- 8347342 TI - Structure of platelet-derived growth factor: implications for functional properties. PMID- 8347343 TI - A novel monoclonal antibody dependent on domain 5 of the platelet-derived growth factor beta receptor inhibits ligand binding and receptor activation. AB - Platelet derived growth factor (PDGF) induces activation of the protein tyrosine kinase domain of the PDGF receptor, resulting in receptor dimerization and the initiation of mitogenesis in responsive cells. In order to identify domains of the receptor involved in these processes, a panel of monoclonal antibodies (MAbs) against the extracellular region of the human PDGF receptor was developed and screened to identify which of these specifically block PDGF binding. One of these, MAb 2A1E2, binds PDGF beta receptor with high affinity and blocks PDGF BB binding in a whole cell binding assay with an IC 50 of 0.1 nM. Inhibition of binding results in the inhibition of ligand-induced receptor phosphorylation, dimerization and mitogenesis in cells expressing the PDGF beta receptor. MAb 2A1E2 has been mapped to the fifth Ig domain of the PDGF beta receptor, implying that this domain is important for ligand binding, dimerization and/or activation. The potency of MAb 2A1E2 for inhibiting PDGF BB binding indicates that this antibody is ideally suited to identify and characterize PDGF BB-induced biological responses. PMID- 8347344 TI - Expression and regulation of insulin-like growth factor-I in the rat incisor. AB - Growth factors play an important role in the regulation of cell growth, division and differentiation. In this study the distribution and regulation of insulin like growth factor-I (IGF-I) in the continuously erupting rat incisor was determined by immunohistochemistry. Results were evaluated both visually and with a computer-based image analysis system. The distribution and intensity of IGF-I immunoreactivity varied with developmental stage of the rat incisor. Strong IGF-I immunoreactivity was observed in differentiating odontoblasts and ameloblasts. The most intense immunoreactivity was observed in secretory ameloblasts, secretory odontoblasts and in maturation ameloblasts. Staining was weak or absent in post-secretory ameloblasts but persisted in post-secretory odontoblasts. Weak to moderate immunoreactivity was also seen in cells of the stratum intermedium and in the reduced enamel epithelium. Surrounding alveolar bone showed strong IGF I immunoreactivity in osteoblasts and in the stratum basale and stratum spinosum of the adjacent labial gingival epithelium. In order to assess the role of GH in IGF-I expression, GH (65 micrograms/100 g bw) was administered for six days to dwarf GH deficient rats, producing a significant increase in body weight (P < 0.01). Measurements at different stages of odontogenesis showed that the staining intensity of secretory ameloblasts (P < 0.01) and maturation ameloblasts (P < 0.001) was significantly different between untreated and treated animals. These results indicate that IGF-I is present in cell populations of the enamel organ of the rat incisor found previously to exhibit growth hormone receptors, and that expression of IGF is GH dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347345 TI - Increased basic fibroblast growth factor (bFGF) accumulation and distinct patterns of localization in isoproterenol-induced cardiomyocyte injury. AB - Basic FGF is a multifunctional protein which promotes regeneration in several tissues. To investigate involvement in cardiac injury-repair, bFGF accumulation and localization was examined in hearts of rats injected with a single high dose of isoproterenol. The bFGF content of cardiac extracts was analyzed at 6 and 24 hours as well as 1, 4, and 6 weeks by western blotting of heparin-sepharose-bound fractions. The 18 kilodalton bFGF species showed an approximately 2-fold increase in extracts from treated animals compared to non-treated controls. A transient rise in a 21-23 kilodalton bFGF species was seen at 24 hours after treatment. An induction of bFGF mRNA was also observed in treated animals. To localize bFGF in vivo, immunofluorescent labelling with specific antibodies was used at 4-24 hours and 1-4 weeks after treatment. Simultaneous labelling for the cytoskeletal proteins vinculin or vimentin was employed to identify viable myocytes or non muscle interstitial cells, respectively. Necrotic myocytes, identified by loss of vinculin, displayed a pronounced increase in cytoplasmic anti-bFGF staining compared to adjacent normal myocytes. This increase occurred prior to and may play a role in promoting mobile cell migration and proliferation in areas of necrosis. Viable cardiomyocytes adjacent to fibrotic regions displayed strong pericellular anti-bFGF staining and, occasionally, were also stained by anti vimentin antibodies, suggesting reexpression of an embryonic phenotype and thus an attempt for regeneration. These data showing increased accumulation and distinct patterns of localization of bFGF in the hearts of isoproterenol-treated animals suggest that this growth factor plays a role in short-term as well as long term response of the myocardium to injury. PMID- 8347346 TI - Dose responsive effects of PDGF-BB, PDGF-AA, EGF, and bFGF on granulation tissue in a guinea pig partial thickness skin excision model. AB - A guinea pig partial thickness skin excision model was used to evaluate the effects of recombinant human PDGF-BB, PDGF-AA, EGF, and bFGF on granulation tissue (neodermis) formation. These growth factors tended to increase the thickness of the granulation tissue bed when assessed histologically at day 7. Using only four animals per group, PDGF-BB at 30 and 100 micrograms/ml consistently and significantly increased the thickness of the granulation bed 2-3 times that of control. Except for the increased thickness, the granulation tissue appeared normal. PDGF-AA and EGF also significantly increased the granulation tissue thickness, and bFGF gave indications of an effect. There was no evidence of synergistic effects between PDGF-BB, EGF, and/or bFGF. PMID- 8347347 TI - Evaluation of PDGF-BB, PDGF-AA, bFGF, IL-1, and EGF dose responses in polyvinyl alcohol sponge implants assessed by a rapid histologic method. AB - Polyvinyl alcohol sponge implants were used in rats, mice, and guinea pigs to determine dose responses of growth factors. Eight differently treated sponges per rat or guinea pig (4/mouse) were injected with test material on alternate days and evaluated at day 8. Much of the observed response occurred in and around the capsule and was manifest as densely cellular granulation tissue. Including this capsular response in a single histologic slide ranking system provided a more sensitive and faster method of assessing growth factor effects than measurement of connective tissue ingrowth alone. Clear dose responsive effects were seen with recombinant human PDGF-BB, PDGF-AA, bFGF, and IL-1 beta, while EGF gave a lesser response. Lipopolysaccharide did not affect the connective tissue response, alone or in combination with PDGF-BB. PDGF-BB was tested in each species, and the dose response characteristics were qualitatively and quantitatively similar across species. PMID- 8347348 TI - Human macrophage colony-stimulating factor induces the differentiation of trophoblast. AB - When human cytotrophoblastic cells in the early stage of pregnancy were cultured in a serum-free medium in the presence of human macrophage colony-stimulating factor (M-CSF), the cytotrophoblastic cells fused and formed a typical syncytiotrophoblast which had a dense distribution of microvilli revealed under an electron microscope. On the other hand, cytotrophoblasts incubated with anti-M CSF antibody showed hardly any syncytiotrophoblast formation. Following this finding, we studied the differentiation of chorionic cells from the viewpoint of hormone secretion. When cytotrophoblasts were incubated in the presence of M-CSF, the supernatant of the culture showed an increase in human chorionic gonadotropin and human placental lactogen levels in proportion to the concentration of M-CSF added. When cytotrophoblasts were incubated in the presence of anti-M-CSF antibody or anti-fms antibody, human chorionic gonadotropin and human placental lactogen secretion were suppressed. Thus, M-CSF was morphologically and endocrinologically found to induce the differentiation of chorionic cells. PMID- 8347349 TI - Localization of the GTP-binding protein Gi alpha in myelomonocytic progenitor cells is regulated by proliferation (GM-CSF, IL-3) and differentiation (TNF) signals. AB - We have examined the role of Gi alpha in haemopoietic cells using the myelomonocytic progenitor cell lines FDC-P1 and WEHI-3B (JCS). During growth factor-dependent proliferation of FDC-P1 cells Gi alpha was found predominantly in the nucleus and associated with the plasma membrane. Following removal of growth factor, Gi alpha accumulated in the cytoplasm and at the plasma membrane. Treatment of FDC-P1 cells with pertussis toxin (PT) completely inhibited translocation of Gi alpha to the nucleus and reduced the sensitivity of FDC-P1 cells to the proliferative effects of growth factors, indicating that translocation of Gi alpha plays a regulatory role in, but may not be essential for, cell division. Gi alpha initially associated with DNA during S/G2 of the FDC P1 cell cycle but separated from condensing chromosomes during mitosis. In contrast to FDC-P1 cells, WEHI-3B (JCS) cells proliferate in the absence of added growth factors but can be induced to differentiate by TNF-alpha. In proliferating JCS cells Gi alpha was again associated with the nucleus but when proliferation was inhibited by TNF-alpha, Gi alpha accumulated in the cytoplasm with none detected in the nucleus. Thus the cytokine regulated accumulation of Gi alpha at different intracellular sites correlated with the ability of the cell to progress through the proliferative cycle. When the tyrosine kinase inhibitor genistein was added to FDC-P1 cells prior to stimulation with IL-3 or GM-CSF, proliferation was almost completely inhibited but translocation of Gi alpha was not affected, suggesting that tyrosine phosphorylation was not involved in G protein translocation but was essential for cytokine induced cell division. Cholera toxin (CT) also inhibited proliferation of FDC-P1 cells but had no effect on translocation of Gi alpha to the nucleus. The near complete inhibition of cell division by genistein and CT without a corresponding effect on Gi alpha movement indicates that Gi alpha can be regulated independently of tyrosine kinase and adenylyl cyclase activities, respectively. PMID- 8347350 TI - Characterization of a saporin mitotoxin specifically cytotoxic to cells bearing the granulocyte-macrophage colony-stimulating factor receptor. AB - When granulocyte-macrophage colony-stimulating factor (GM-CSF) is chemically conjugated to the ribosome-inactivating protein saporin, the resulting protein conjugate is highly toxic for cells expressing the GM-CSF receptor. Structural and Western blot analyses of the purified conjugate establish that it contains equimolar amounts of the starting materials and is free of any contamination by the non-conjugated components. The resulting bifunctional reagent is specifically cytotoxic to cells expressing the GM-CSF receptor, but is ineffective to cells that do not express the receptor. The cytotoxic activity is inhibited in a dose dependent manner by GM-CSF, but not by any one of five other peptide growth factors. This is the first report of a mitotoxin for cells that express the GM CSF receptor and which promises to be a valuable tool to study the expression of the GM-CSF receptor in normal and pathological states. PMID- 8347351 TI - Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. AB - C3H10T1/2 cells are an established mesenchymal stem cell line which can differentiate into muscle, fat and cartilage cells when treated with azacytidine. Bone morphogenetic protein-2 (BMP-2) caused a dose dependent differentiation of these cells into fat, cartilage and bone cells-low concentrations favoring adipocytes and high concentrations chondrocytes and osteoblasts. The differentiated phenotypes were stable in the absence of BMP-2. Furthermore, the addition of other growth factors during the differentiation process altered the frequency of the differentiated colony formation. Transfection of the C3H10T1/2 cells with a BMP-2 cDNA also induced a phenotypic change from the parental fibroblast to adipocytes and osteoblasts. Our results in this model system indicate that a single protein factor can cause differentiation of a stem cell line to multiple phenotypes, that phenotypes induced can be regulated by factor concentration, and that other factors can also influence BMP-2 induced differentiation. PMID- 8347352 TI - Enhanced bFGF gene expression in response to transforming growth factor-beta stimulation of AKR-2B cells. AB - Treatment of quiescent cultures of mouse embryo-derived AKR-2B cells with transforming growth factor beta resulted in an induction of basic fibroblast growth factor (bFGF) mRNA and bFGF protein in the stimulated cells. In contrast to bFGF, acidic fibroblast growth factor (aFGF) was not induced by TGF beta. The mitogenic effect of transforming growth factor beta on AKR-2B cells may be mediated by the induction of bFCF in these cells. PMID- 8347353 TI - Videothoracoscopic surgery. AB - Although thoracoscopy has been used for diagnostic and minor therapeutic procedures for many years, there have been few reports of its use in performing major intrathoracic procedures which have traditionally required formal thoracotomy. We report our initial experience in this field. Fifty patients (M:F = 1.63:1, mean +/- SD age = 41.8 +/- 20.4 years, range = 14-80) underwent 54 endoscopic intrathoracic operations. The procedures carried out included wedge excision of solid pulmonary mass (10), pleurectomy (25), lung biopsy (14), and miscellaneous procedures (5). Under general anaesthesia a laparoscope attached to a video monitor was introduced into the chest. One or two additional stab incisions were made as needed for the introduction of standard surgical or endoscopic instruments and staplers. There were no deaths. One patient developed a second pneumothorax 7 days after endoscopic pleurectomy, necessitating open pleurodesis. All patients were discharged home between 2 and 11 days after surgery (mean +/- SD = 3.8 +/- 2.0 days). Endoscopic thoracic surgery is a safe and useful technique for certain cases. It merits further investigation and assessment. PMID- 8347354 TI - Ischemic tolerance of the arrested heart during warm cardioplegia. AB - Normothermic blood cardioplegia has recently generated interest as an alternative method of myocardial protection during cardiopulmonary bypass (CPB) surgery. One disadvantage is the obligatory interruption of coronary flow during the distal coronary anastomosis. This study was designed to determine the safe normothermic ischemic time of the arrested and decompressed heart. Under normothermic CPB (37 degrees C), initial cardioplegic arrest was induced with 750 cc of warm (37 degrees C) hyperkalemic blood cardioplegia in 21 adult dogs. The heart then received warm blood cardioplegia either continuously (50 cc/min), every 5 min (250 cc each) or every 10 min (350 cc each) for a total equivalent ischemic time of 30 min (n = 7 in each group). Left ventricular pressure-volume (PV) loops were measured by micromanometer and conductance (volume) catheters before, at 60 and 90 min after aortic cross-clamping. Systolic function was measured as the preload recruitable stroke work area derived from the stroke work-end diastolic volume relationship, and the diastolic stiffness constant (k) was derived from the exponential diastolic PV relationship. The q5 min group sustained minor deterioration in diastolic function while its systolic function was well maintained during recovery. There were significant reductions in both the diastolic and systolic functions in the q10 min group. The maximum drops in the septal wall pH during aortic cross-clamping were 0.05 +/- 0.02 (not significant), 0.19 +/- 0.06 (P < 0.05), and 0.40 +/- 0.09 (P < 0.01) for the continuous, q5 min and q10 min groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347355 TI - Laryngotracheal resection and reconstruction for postintubation subglottic stenosis. Lessons learned. AB - Between 1981 and June 1992, 26 consecutive patients with a postintubation subglottic stenosis (21 circumferential, 2 anterolateral) underwent the Pearson operation. Subglottic stenosis resulted from a complication of mechanical ventilation with endotracheal intubation with (n = 14) or without (n = 12) tracheostomy (median placement: 25 days). One patient had an associated laryngopharyngeal and tracheoesophageal fistula. Overall, the upper limit of the stenoses lay 1.8 +/- 0.3 cm below the vocal cords, falling in the range of 1 to 2 cm in 88% of patients; they measured 2.9 +/- 0.8 cm in length and the diameter at the level of the maximum stenotic process was 0.5 +/- 0.1 cm. Operations were performed without dissection of the recurrent nerves and plicature of the membranous trachea. Because of scarred mucosa at a higher level, one vertical section of the posterior cricoid plate with interposition of autogenous costal cartilage and 2 subtotal cricoid plate resections with stenting were necessary. The mean length of resection was 3.6 +/- 0.8 cm (range: 2-5 cm) and 88% of them ranged within 2.8 and 5 cm. Twelve thyrohyoid and 3 supralaryngeal releases were performed. Six patients required postoperative tracheostomy, but all were extubated within 24 h. Good results were obtained in 24 (96%) surviving patients; 1 failure and 1 postoperative death (sudden myocardial infarction) occurred. The results confirm that the Pearson operation is an adequate treatment for subglottic stenosis extending up to 1 cm below the vocal cords and measuring up to 6 cm in length. Dissection of both the recurrent nerves, plicature of the membranous trachea, postoperative decompressive tracheostomy and stenting are not necessary. PMID- 8347356 TI - Disability and distress following cardiac surgery in patients over 70 years of age. AB - We have reviewed the outcome in a consecutive series of 254 patients over the age of 70 undergoing cardiac surgery between 1987-89. Of the patients, 62% were male and the median age was 73 years. Operations included: coronary bypass 57%, valve replacement 26%, combinations 14% and other procedures 3%. The hospital mortality was 7.5% and late mortality was 13.8%. Complications included: intraaortic balloon 6%, resternotomy for bleeding 4%, permanent pacing 3%, chest infection 14%, tracheostomy 5%, major cerebrovascular events 3% and minor 4%. Eighty-two percent left the intensive care unit within 24 h and 89% left hospital within 8 days. Two questionnaires (York University) were sent to 207 patients believed to be alive in order to evaluate the change in their quality of life following surgery. Of the 207 questionnaires 197 (95%) were returned, 7 of which were from relatives of patients who had died and 7 were incomplete. The responses of 183 assessable patients (at a mean follow-up of 36 months) were converted into Rosser disability (I-VIII) and distress (A-D) groups. There was a decrease in disability and distress in 60% and 67%, respectively, no change in 34% and 30% and deterioration in 6% and 3%. Cardiac surgery can be carried out in elderly patients with an acceptable early morbidity and mortality, and although many patients show sustained improvement in their quality of life, this was not demonstrated in about a third of patients. As the emphasis in the elderly should be on quality of life we ought to continue to concentrate on careful selection in this age group. PMID- 8347357 TI - Does modern cardiac surgery require conventional intensive care? AB - We considered that, with modern perfusion equipment and mildly hypothermic cardiopulmonary bypass, protracted post-operative ventilation in an intensive care unit (ITU) is no longer required after most cardiac operations. We used a three-bedded cardiac recovery area (CRA) within the operating suite for 1,000 patients between January 1990 and June 1991. Forty-five patients with special needs were managed in the ITU. The time to extubation (T50%; range) for coronary bypass, aortic valve, mitral valve, and double-valve patients was 2.0 (0-42), 2.5 (0-12), 3.0 (0-15), and 3.0 (1-36) hours, respectively. Recovery beds were re used allowing 5-6 operations daily. The difference in nursing staff complement for a CRA versus ITU bed was 4.5/7.8. Patient management was by nurse specialists supported by cardiac surgeons. Intervention by cardiac anaesthetists or intensivists was limited to specific ventilatory problems or renal failure. The early extubation policy failed in ten patients (five coronary, three aortic, one mitral and one double-valve patient) through poor pre-operative respiratory function, left ventricular failure or intra-operative events. The overall mortality in CRA was 1.4%. The mean duration of post-operative stay was 7 days (range 5-12). We conclude that a CRA staffed by nurse practitioners provides a safe and effective alternative to the anaesthetist-managed ITU. A rapid turnover of CRA beds removes the constraints of ITU bed availability. PMID- 8347358 TI - Chronic rejection following lung transplantation. Incidence, time pattern and consequences. AB - The long-term prognosis following lung transplantation (LTX) depends mainly on the development of chronic rejection which appears clinically as deterioration of the lung function while, histologically, obliterative bronchiolitis (OB) is found. However, it still remains questionable whether heart-lung (HL), double or single lung (DL/SL) transplants behave similarly with regard to incidence and time pattern. Eighty-two patients, transplanted until August 92, were analyzed. Early and late deaths within 180 days postoperatively were excluded. A total of 64 patients at risk could be evaluated. By repeated lung function tests, obstructive airway disease was defined by a drop of 25% or more of the forced expiratory volume in one second (FEV1) in percent of the inspiratory vital capacity. RESULTS: The functional optimum after transplantation was reached after a comparable time-span postoperatively in all groups. Chronic deterioration of the lung function developed earlier following DLTX compared to HLTX and SLTX. Obstructive airway disease was diagnosed in 9/20 (45%) HL, 7/19 (37%) DL, and 7/25 (28%) SL patients. Of these, 4 died and 4 had to be retransplanted for the disease while an additional 15 patients are currently under investigation. It is concluded that the development of obstructive airway disease represents a serious problem in all types of lung transplantation. There is a tendency to earlier development following DLTX--perhaps caused by the greatest immunological potential in this group of patients. PMID- 8347359 TI - Recovery of myocardial function. The ultimate target of coronary revascularization. AB - Recovery of myocardial contraction represents an important target of coronary revascularization and the preoperative recognition of viable akinetic (hibernating) myocardium is a crucial point of the preoperative investigation of patients with chronically depressed left ventricular function. In 14 patients dobutamine infusion during echocardiography was utilized to evoke the contractile reserve retained by viable akinetic segments. Redistribution of thallium(TI)-201 after the rest injection was also used to assess the viability of akinetic areas. The wall motion response to dobutamine infusion predicted immediate postoperative improvement in 85 of 93 segments (sensitivity 91.3%) and identified 25 of the 32 segments which did not exhibit early postoperative improvement (specificity 78.1%). Rest redistribution of TI-201 demonstrated high sensitivity (93.0%) but low specificity (43.7%) for predicting the early recovery of regional wall motion. When late recovery was also considered, the specificity of this method increased to 64.0%. Rest distribution of TI-201 identifies viability which is not necessarily associated with the early recovery of function postoperatively. When the echo-dobutamine test is positive, on the other hand, the recovery of function usually occurs immediately after revascularization and the operative risk is expected to be low even in the presence of severely compromised left ventricular function. PMID- 8347360 TI - Iatrogenic clubbing of the fingers. AB - We report on a 39-year-old female who had been operated on for an atrial septal defect at the age of 14 years. On operation the inferior vena cava was iatrogenically misdirected into the left atrium. The cyanotic patient, in functional group IV of the NYHA classification, with polyglobulia and clubbing of the fingers was successfully reoperated after 25 years. PMID- 8347361 TI - Left and right ventricular diverticula, ventricular septal defect and ectopia cordis in a patient with Cantrell's syndrome. AB - A patient with Cantrell's syndrome is presented with ectopia cordis, ventricular septal defect and a left ventricular as well as a right ventricular diverticulum. One-stage correction was performed with resection of both diverticula. Closure of the ventricular septal defect was complicated due to exposure problems as a result of the malposition of the heart. Although the presentation of Cantrell's syndrome can be variable, one-stage repair is technically feasible and should be considered as the treatment of choice in this rare syndrome. PMID- 8347362 TI - Is lung cancer resection justified in patients aged beyond 70 years? PMID- 8347363 TI - Breast and cervical cancer screening of poor, elderly, black women: clinical results and implications. Harlem Study Team. AB - Our objective is to describe the clinical findings from a nurse-practitioner based breast and cervical cancer screening program for poor, elderly, black women. We designed a cross-sectional descriptive study set at an urban public hospital medical clinic. All women 65 years of age and older were eligible to be screened. We measured these main outcomes: rates of participation, abnormal tests, and neoplasia. Women were offered screening during a routine visit. Of 689 women, 491 (71%) participated. Mammography was completed by 66% of women; one had stage 1 cancer, and 76% were negative. Among the women (24%) with abnormal mammograms, the overwhelming majority were diagnosed with benign lesions. For ten of 450 women completing Papanicolaou (Pap) smears, results were suspicious or positive for malignancy, for a prevalence rate of 22.2/1,000 (95% confidence interval [CI] = 8.6/1,000 to 35.8/1,000). Three were subsequently designated falsely positive; five had confirmed cervical neoplasia; and two had other reproductive malignancies. Two women with negative smears also had neoplasia: one with vulvar cancer and one with human papilloma virus (HPV) infection and cervical neoplasia, for a total of six cervical neoplasias. Interestingly, one fifth of women with a hysterectomy had an intact cervix, including one with cervical neoplasia. Nearly one-third of women with abnormal Paps or mammograms failed to complete follow-up. Success of screening programs for the elderly will depend on the risk group targeted, careful examination, degree of sensitivity and specificity of the tests, and acceptability of follow-up diagnosis and treatment. PMID- 8347364 TI - Cost-effectiveness of two nurse-led programs to teach breast self-examination. AB - The cost-effectiveness of breast cancer screening that includes breast self examination (BSE) has not been investigated, in part because the costs and effects of programs to teach BSE are not well known. I used data from a randomized, controlled trial and national surveys to compare the benefit, cost, and cost-effectiveness of two one-year, nurse-led programs to teach BSE in a medical practice setting. One program (Mammacare, or MAM) used manufactured silicone models to develop tactile skills; the other program (Traditional, or TRAD) stressed knowledge and examination techniques. I defined benefit as the marginal one-year increase in the number of women in an "average" adult primary care office practice who performed competent and frequent BSE. I defined cost as the marginal increase in the resources used to teach BSE and in the resources used as a result of performing BSE. Cost-effectiveness equaled the cost per competent, frequent BSE examiner added. The "average" practice was derived based on estimates from national surveys of physicians and medical practices. The MAM program's benefit was fivefold greater than the TRAD program's; its total cost was more than threefold greater; and its cost per competent, frequent examiner added was 32% lower. Yet, regardless of the program, one year following teaching only 15%-28% of women were competent, frequent performers. Cost-effectiveness was sensitive to the definition of benefit. Cost-effectiveness was also sensitive to some costs, but generally these sensitivities did not alter the relative cost effectiveness of the two programs. The cost of teaching BSE was substantial. Benefit, cost, and cost-effectiveness varied by program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347365 TI - Risk for cardiovascular disease in the elderly and associated Medicare costs: the Framingham Study. AB - Studies of young, employed populations have established an association between risk factors for cardiovascular disease and health care costs, but an association has never been demonstrated in an elderly population. For the surviving elderly cohort (63 to 93 years of age) of the Framingham Heart Study (n = 1,053), we estimated a model regressing Medicare reimbursements per beneficiary over two years (1984 and 1985) on the two-year probability of cardiovascular disease at Exam 17 (1982 or 1983), controlling for other risk factors and prior health services use. Using the coefficient for the two-year probability for cardiovascular disease, we estimated Medicare cost ratios and dollar values associated with elevated compared with nonelevated risk for 12 risk profiles for cardiovascular disease. The average level of risk for cardiovascular disease in the elderly is associated with Medicare claims costs that are 19% higher (95% confidence interval [CI] = 10%, 29%) than those for persons with no elevated risk, equivalent to an average of $371 per elderly beneficiary or $9.3 billion per year in Medicare expenditures. Smoking is associated with 16% (95% CI = 8%, 24%) higher Medicare costs than nonsmokers' costs. Systolic blood pressure of 160 mm Hg is associated with 11% (95% CI = 6%, 16%) higher Medicare costs, compared with a systolic blood pressure of 140 mm Hg. A total blood cholesterol level of 260 mg/dL is associated with 6% (95% CI = 3%, 9%) higher Medicare costs, compared with a total blood cholesterol of 180 mg/dL. Additional studies are needed to help calculate the cost-effectiveness of risk reduction for the elderly. PMID- 8347367 TI - Smokeless tobacco use among children: the New Hampshire Study. AB - Rural public school children initially in grades 4, 5, and 6 participated in a 36 month follow-up study of substance abuse prevention. Children completed self report questionnaires at baseline and annually for three years after the introduction of prevention programs. We compared outcomes of (1) a comprehensive school curriculum ("Here's Looking at You, 2000"), (2) the curriculum plus a parenting course ("Parent Communication Course") and a community task force (Johnson Institute Model), and (3) control condition. Neither the curriculum nor the curriculum plus parent and community intervention had any effect on smokeless tobacco use by this preadolescent and young adolescent population. We used stepwise logistic regression to determine prediction models for smokeless tobacco use. Initiation of smokeless tobacco use is associated with sex, grade, and having friends who use drugs. Although regular use increases with grade, poor family relations, and low school satisfaction, the greatest risk factor was ever trying smokeless tobacco. We describe the culture of smokeless tobacco use in this population, and we discuss the implications of our research for smokeless tobacco use prevention. PMID- 8347366 TI - Demographic and educational differences in smoking in a tobacco-growing state. AB - National studies have documented an excessive rate of cigarette smoking in black men; however, a 1987 survey conducted in two urban areas in South Carolina documents a high rate of smoking in young white men with fewer than 12 years of education (67%; 95% confidence interval [CI] = 58.3, 75.7). Differences in smoking rates by educational level were significant only for those younger than 40. Young blacks were less likely to smoke and smoked fewer cigarettes than whites. As a result, the population burden of cigarettes in young black men with fewer than 12 years of education was only 27% of the burden carried by their white peers. Television, physicians, and radio were all seen as likely sources of health information to prevent heart disease, but newspapers were less likely to be cited by those younger than 40 or by those with fewer than 12 years of education. Reported physician counseling for smoking cessation did not differ significantly by race, sex, or educational level of the patient, but reported counseling was higher for individuals with a personal history of cardiovascular disease (odds ratio [OR] = 2.32, CI = 1.27, 4.25) and somewhat lower for the elderly. We highlight the population burden of cigarettes, a predictor of the eventual disease burden attributable to smoking, as a useful priority measure for smoking intervention efforts. PMID- 8347369 TI - The costs and benefits of breast cancer screening. AB - The costs and benefits of breast cancer screening can be placed in the framework usually used for sensitivity and specificity. All those screened incur the costs associated with the test. In addition, only the segment of the true positives who, in the absence of screening, would die of their disease but with screening will survive to die of another cause truly benefit; all other true positives acquire lead time without benefit. In the Canadian National Breast Screening Study, simpler treatment of screen-detected cancer was not achieved. The true negatives benefited from reassurance, but the majority were not at risk of breast cancer anyway. The false negatives were disadvantaged from false reassurance, but in practice the percentage is low, and the consequences are not dire. There are major costs associated with the false positive state, including anxiety, unnecessary biopsies, and residual scarring; major endeavors are justified to reduce them and improve the specificity of screening. In practice, with no benefit demonstrated for women 40-49 years of age, the costs are too great to justify continuation of screening this age group merely in the hope that benefits will eventually be demonstrated. For women older than 50, the degree of benefit may have been overestimated, especially in an era when improvements in therapy affect screen-detected and nonscreen-detected cases alike. We may have overestimated the benefit-cost ratio of screening this age group also; thus, careful monitoring of the outcome of ongoing programs over the next few years is essential. PMID- 8347368 TI - Improvements in cholesterol-related knowledge and behavior and plasma cholesterol levels in youths during the 1980s. AB - This article examines cholesterol-related knowledge, cholesterol-related behaviors, and plasma cholesterol levels in 12-24-year-olds, using data collected from four community-based cross-sectional surveys conducted 1979-1980, 1981-1982, 1985-1986, and 1989-1990. Participants included 1,552 individuals from randomly sampled households in two control cities (San Luis Obispo and Modesto, California) of the Stanford Five-City Project. Over the eleven-year study period, cholesterol-related knowledge improved in both control cities (P < .0002). Cholesterol-related behavior (P < .0003) and plasma cholesterol levels (P < .002) significantly improved only in San Luis Obispo (a college city with more 19-24 year-olds and a better-educated population than Modesto). In general, knowledge and behavior scores and plasma cholesterol levels were lower in these 12-24-year olds than in 25-74-year-olds, although trends at all ages were similar over time and by demographic variables. Although the cholesterol-related interventions that began in the mid-1980s primarily targeted adults, these 12-24-year-olds' cholesterol-related knowledge improved (as did, to a lesser extent, their cholesterol-related behavior and plasma cholesterol levels). These findings have implications for upcoming youth-related cholesterol interventions. PMID- 8347370 TI - Mammography in West Virginia. AB - A questionnaire was sent in 1988 to all sites conducting mammographic studies registered with the radiologic licensing division of the West Virginia State Department of Health Laboratory Services to determine the number of women served and the costs of the procedures. The number of sites, 61, appears excessive in view of the small number of women many of them screened during the course of a year and the high charges. Copies of the report on the questionnaire results were sent to agencies and other groups within the state to urge initiation of a more cost-effective system; however, four years later the number of units had increased substantially, and no coherent plan had been formulated. The report was helpful to members of the state legislature in their decision to mandate insurance coverage for women according to the American Cancer Society guidelines. PMID- 8347371 TI - Mammography in the 1990s: a plea for objective doctors and informed patients. AB - Mammography screening is increasingly promoted as a means to avoid death from breast cancer. Although some randomized trials have shown a mortality benefit in the older screened groups, not all the results have been statistically significant; benefit has not been shown in younger age groups. Mammography detects smaller lesions than physical examination, but the only randomized trial comparing the mortality benefits of mammography and physical examination shows no benefit for mammography. The systemic nature of breast cancer raises questions about the theoretical mortality benefit of screening. Patients undergoing mammography may experience unexpected anxiety about the results. Candidates for screening should be routinely informed of these issues. PMID- 8347373 TI - Genetic metabolic disease: a paradigm for preventive health care. PMID- 8347372 TI - Preventing Vibrio vulnificus infections: who should bear responsibility? PMID- 8347374 TI - Inherited metabolic diseases: collaborating for the health of all children. PMID- 8347376 TI - Decrease of isoprene concentrations in blood during general anesthesia. AB - Isoprene is present in human breath and in human blood. The fact that isoprene concentrations in breath are linked to states of sleep and wakefulness led us to study its concentration in blood of 12 patients before, during, and after general anesthesia. Isoprene concentrations in blood of patients before anesthesia were 3.3 +/- 1.6 micrograms/liter. During anesthesia, isoprene concentrations decreased to 0.9 +/- 0.5 micrograms/liter. One hour after the end of anesthesia isoprene increased to levels similar to or higher than the preanesthetic ones. PMID- 8347375 TI - Molecular genetic aspects of cardiomyopathy. AB - Cardiomyopathies are a major cause of mortality and morbidity and this spectrum of disorders tops the list of diseases leading to cardiac transplantation. While significant gains have been made during the past decade clinically, knowledge of the molecular aspects of these disorders has taken longer to advance. During the past 5 years, however, molecular genetic information on a variety of primary cardiomyopathies, such as familial hypertrophic cardiomyopathy and X-linked dilated cardiomyopathy, has been obtained. Other primary and secondary myocardial diseases are now under study with advances occurring more regularly. The purpose of this review is to outline the major advances thus far described for some primary and secondary cardiomyopathies, as well as detailing the slower progress seen for others. PMID- 8347377 TI - A glucokinase-like enzyme carries out glucose phosphorylation in capillaries of normal and spontaneously hyperglycemic rabbits. AB - We have studied glucose phosphorylation at increasing glucose concentrations (1, 5, 10, 25, 50, and 100 mmol/liter) in capillaries of the choroidocapillary lamina from the eye of normal female albino rabbits (n = 10; body wt 1800-2000 g; mean +/- SEM morning glycemia: 147.77 +/- 4.02 mg/dl) and from the eye of spontaneously hyperglycemic rabbits (n = 5, body wt 1800-2000 g, mean +/- SEM morning glycemia; 211.00 +/- 10.76 mg/dl). In the 3000g supernatant of capillary homogenates, the glucose phosphorylating activity (NADP reduction measured as optical density change at 366 nm at pH 7.5) increased progressively with the rise of glucose concentration (r = 0.36; P < 0.05), approaching the peak at high glucose level (25 mmol/liter), with values ranging from 5.32 +/- 0.46 (SEM) nmol/min/mg protein to 7.14 +/- 0.74 (+34.21%, P < 0.01). When measured at a more alkaline pH (8.2) the glucose phosphorylation was higher than at pH 7.5 and retained the responsiveness to increasing glucose concentrations. These kinetic characteristics differ from those seen in most tissues and are somewhat reminiscent of those shown by hepatic glucokinase. Indeed, by subtracting the activity at 1 mmol/liter glucose from that at higher glucose concentrations, we calculated the "glucokinase component" which together with the "hexokinase component" form the total glucose phosphorylating activity. Glucose phosphorylation in capillaries from spontaneously hyperglycemic rabbits was lower than normal (values: 3.66 +/- 0.31 vs 5.32 +/- 0.46 of the normal rabbits; 31.20%; P < 0.05). This could contribute to the hyperglycemia by reducing glucose utilization. However, in these animals the enzyme activity retained the responsivity to increasing glucose concentrations (r = 0.41, P < 0.05). Therefore, the actual capillary glucose phosphorylation in these animals would depend upon both the enzyme level (which is reduced) and the glucose concentration (which is increased). Due to the in vivo inhibition of the hexokinase component, the glucokinase component may be predominant in vivo, making the stimulating effects of hyperglycemia much more pronounced than it would appear from our data in vitro. This may lead to glucose overutilization. These kinetic characteristics of glucose phosphorylation in capillaries might be relevant to the mechanisms leading to diabetic microangiopathy. PMID- 8347378 TI - Regulation of orotic acid biosynthesis and excretion induced by oral glutamine administration in mice. AB - Glutamine, the most abundant amino acid in blood and tissues, is degraded by the renal and splanchnic tissues, especially the small intestinal mucosa. Due to the activity of glutaminase, it may be broken down in these tissues and contribute to ammoniagenicity. Glutamine, either directly or through ammonia production, may act as a nitrogenous source for pyrimidine biosynthesis. We have evaluated the effect of glutamine on orotate metabolism in mice, by gavaging (ig) L-glutamine, 1.0 to 4.0 mmol/100 g of body wt/day, during 6 weeks of experimentation. Glutamine at doses of 2.5 to 4.0 mmol/100 g of body wt caused a significant increase in plasma ammonia and urinary orotate. The regulation of the orotic acid biosynthesis and excretion was studied by testing the effects of various inhibitors in mice force-fed with glutamine (4 mmol/100 g of body wt, ig). The orotic aciduria was insensitive to acivicin (1 and 5 mg/100 g of body wt, ip), a specific inhibitor of the cytoplasmic carbamyl phosphate synthetase-II, thus pointing toward the mitochondrion as the principal source of carbamyl phosphate. Cycloheximide (15 and 100 mg/kg of body wt, ip) caused a significant decrease in urinary orotate indicating that the induction of orotate synthesis by glutamine may be associated with the translation of a specific protein. However, orotate excretion was significantly decreased by N-(phosphonoacetyl)-L-aspartate (PALA) (5 mg/100 g of body wt, ip) due to its inhibitory effect on the aspartate transcarbamylase activity. There was a significant increase of urinary orotate following ingestion of adenine supplemented diets (0.1% and 0.2%), suggesting the blockage of the utilization of orotate for nucleotide biosynthesis by glutamine. Since orotate synthesis may also be influenced by ornithine metabolism, we evaluated the effect of glutamine administration on various ornithine metabolizing enzymes. There was a decrease in hepatic ornithine decarboxylase activity with no change in hepatic ornithine aminotransferase activity following the administration of glutamine. This observation indicates that an increased metabolic utilization of ornithine is not responsible for the increase in orotate excretion, which may be caused principally through an effect of glutamine on mitochondrial carbamyl phosphate synthesis. PMID- 8347379 TI - Assay of acyl-CoA dehydrogenase activity in frozen muscle biopsies: application to medium-chain acyl-CoA dehydrogenase deficiency. AB - The acyl-CoA dehydrogenases (ACDs) are mitochondrial enzymes that dehydrogenate acyl-coenzyme A esters of different chain lengths. Inherited deficiencies of these dehydrogenases are commonly associated with muscle weakness and lipid storage. Numerous assays including spectrophotometric, fluorometric, chemical, and radiochemical procedures have been used, but there is need for a rapid, reproducible assay for the different acyl-CoA dehydrogenases in small frozen samples of human muscle biopsies. We describe a comparative study of dye-linked spectrophotometric assays of the long, medium, and short chain acyl-CoA dehydrogenases in frozen rat and human muscle samples. An optimal procedure is described confirming the value of glass-glass homogenization and assay of a 600g supernatant. Higher activities for all acyl-CoA dehydrogenases, citrate synthase, and cytochrome c oxidase were obtained in rat in contrast to human. The substrate linked dye reduction method was found superior to the ferricenium or electron transfer flavoprotein acceptor systems. Application of the phenazine ethosulfate DCPIP-linked method to medium-chain acyl-CoA dehydrogenase (MCAD) was studied in detail and the effect of immunoprecipitation of MCAD allowed for the determination of substrate specificity and the degree of crossover between long-, medium-, and short-chain ACD activity following immunoprecipitation. Finally, a comparison of the specificity and validity of the assay in a patient with MCAD deficiency was performed. PMID- 8347381 TI - Effects of insulin on free amino acids in plasma and the role of the amino acid metabolism in the etiology of diabetic microangiopathy. AB - To investigate if alterations of the amino acid metabolism may play a more important role in the etiology of diabetic microangiopathy than hitherto recognized, free amino acids in plasma were measured by means of high-performance liquid chromatography (HPLC) in healthy individuals (REF) and patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Isoleucine and leucine in IDDM were within normal limits, whereas they were significantly higher in NIDDM (P < 0.01 and P < 0.001, respectively). This was not due to age differences. In order to evaluate the impact of insulin on amino acid metabolism, amino acids were also measured in pregnant women (PREG) undergoing glucose tolerance tests as a screening for pregnancy diabetes and in patients with polycystic ovary syndrome (PCO) undergoing euglycemic insulin clamp tests. Insulin considerably reduced the amino acid concentration. Isoleucine and leucine were particularly depressed. On the whole there was strong covariance between the three branched-chain amino acids, isoleucine, leucine, and valine (P < 0.0001). There was no covariance between amino acid and glucose or HbA1c concentrations. A protein meal strongly stimulated insulin production (+55 mIU/liter), whereas a galactose meal revealed only a minor increase in insulin response (+12 mIU/liter) in contrast to a tolerance test with the same amount of glucose (+67 mIU/liter). It is concluded that disturbed amino acid metabolism may be a more important causative factor in the etiology of diabetic microangiopathy than hitherto recognized and, in addition, that this may affect the therapeutic approach in both IDDM and NIDDM patients. PMID- 8347382 TI - In vivo kinetics of oxidatively modified HDL. AB - The kinetics of oxidatively modified high-density lipoprotein (HDL) in vivo were investigated. 125I-labeled oxidized (Ox) HDL and 131I-labeled native (N) HDL were injected simultaneously into control and WHHL rabbits. The fractional catabolic rates of 125I-labeled Ox-HDL were significantly greater than those of 131I labeled N-HDL in both control (2.52 +/- 0.36/day vs 0.94 +/- 0.02/day) and WHHL rabbits (4.07/day vs 1.32/day). Oxidized HDL was catabolized faster than native HDL and was taken up primarily by the liver, spleen, and kidney. PMID- 8347380 TI - Thiamin-responsive maple syrup urine disease in a patient antigenically missing dihydrolipoamide acyltransferase. AB - Maple syrup urine disease results from inherited defects in human nuclear genes for branched chain alpha-ketoacid dehydrogenase, a mitochondrial multienzyme complex. Thiamin pyrophosphate is necessary for complex activity and a thiamin responsive form of maple syrup urine disease is known. Here we demonstrate the use of [1-13C]leucine oxidation to [13C]O2 quantified in breath samples as a means of assessing whole body leucine oxidation. Analysis of cultured cells from this patient shows the antigenic lack of the E2 subunit, yet she gained branched chain alpha-ketoacid dehydrogenase activity in response to diet supplementation with pharmacologic doses of thiamin. These cultured cells were used to seek a molecular basis for the observed thiamin response. Despite normal thiamin transport in these cells, medium supplementation of up to 1000 thiamin/liter failed to increase complex activity or cause the antigenic appearance of the missing protein. This lack of response in cultured cells suggests that the observed whole body response to thiamin must be a tissue-specific effect in liver, muscle, or kidney. In addition, allele-specific detection of paternal and maternal mutations was used to genotype family members in this pedigree. PMID- 8347383 TI - Primary care and HIV infection in the 1990s. PMID- 8347384 TI - Dementia in general practice: the practical consequences of a more positive approach to diagnosis. AB - General practitioners are often reluctant to administer brief cognitive tests, and to question the relatives of patients who appear to be demented, for fear of causing distress. Diagnoses of dementia are therefore often based on guesswork, and non-demented patients may be rated as cognitively impaired in error. A randomly selected sample of 174 general practice patients aged 80 years and over were asked to complete a simple test of orientation and information in order to assess the usefulness and acceptability of such a procedure. If patients scored 10 points or less out of 12, a relative or other knowledgeable informant was questioned about their changes in mental state and behaviour. Assessments proved acceptable to patients, relatives and doctors; diagnoses were revised in 29 cases; and practical initiatives were proposed in 15 cases. Open discussions with patients and their families proved innocuous and have much to commend them. PMID- 8347386 TI - Does feedback improve the quality of cervical smears? A randomized controlled trial. AB - In a randomized controlled trial three methods of feedback of increasing intensity, directed at 183 doctors taking cervical smears, were compared with respect to their effects on the sampling quality of smears. Overall, feedback was found to have no influence on quality criteria in the crude data analysis. However, a significantly larger decrease in the percentage of smears lacking endocervical cells was found in the groups receiving monthly overviews of their results with peer comparison, when compared with the groups not receiving this type of feedback (odds ratio 0.75). Moreover, feedback appeared to have a clear effect on the presence of endocervical cells among doctors submitting a substantial number of smears in the intervention period, as opposed to those who submitted fewer smears. A positive correlation was also observed between the increase in the group mean of the proportions of smears containing pathological cells and the intensity of the feedback. However, this increase did not reach statistical significance. This study suggests that monthly feedback with peer comparison may have a positive relationship with some aspects of quality improvement in cervical screening. PMID- 8347385 TI - Elderly people's views of an annual screening assessment. AB - A survey was carried out in order to identify elderly patients' perceptions of their health status, their health worries and their opinions regarding health screening before and after the introduction of an annual screening programme. Pre and post-assessment self report, structured questionnaires and standardized, objectively scored, functional and medical assessments were used. The cohort was an age and sex stratified, 20% sample of those aged 75 years and over (133 patients). Results showed that 96% of patients before the assessment and 98% of patients afterwards, considered the annual assessment useful. The domiciliary visit by the health visitors resulted in one third of those patients who perceived themselves to be in good health and three quarters of those who perceived themselves to be in poor health becoming less worried about their health. Only two patients became more worried. Half of those objectively assessed as being in the medium health risk group and 68% of those in the high health risk group became less worried about their health after screening. Despite the majority of patients having welcomed the assessment their visit resulted in false, and potentially harmful, reassurance for a considerable number of individuals objectively assessed as being at medium and high health risk. An adverse consequence of health screening in elderly people may be inappropriate reassurance for those objectively assessed to be at risk. However, screening procedures are a means to an end, not an end in themselves. The identification of those at high risk should see subsequent implementation of services, investigations and increased support to relieve suffering, so it may have been that patients felt less anxious because they were anticipating relief of their problems. PMID- 8347387 TI - Skin biopsies of pigmented skin lesions performed by general practitioners and hospital specialists. AB - The performance of skin biopsies by general practitioners has been examined in several recent studies. The aim of this study was to examine the difference between skin biopsies of pigmented skin lesions taken by general practitioners and those taken by hospital specialists. Reviewing all histopathology records at one hospital over a five year period revealed that there were 1000 patients who had had skin biopsies. General practitioners had carried out skin biopsies for 55% of these patients. Hospital specialists excised significantly more lesions that had increased in size (P < 0.001) or changed in colour (P < 0.001). General practitioners excised more lesions that had bled (P < 0.001). Hospital specialists excised more of the 15 melanomas diagnosed (80%) (P < 0.05), and general practitioners excised more squamous papillomas (P < 0.01). Forty per cent of melanomas excised were not suspected by the clinician. General practitioners were able to detect the majority of suspicious lesions, but because of the uncertainty of clinical diagnosis, all specimen's should be submitted for histopathological diagnosis. It is important that future general practitioners are trained in both the diagnostic and technical aspects of skin biopsy if they intend to perform this minor operation. PMID- 8347388 TI - Analysis of referrals of mental health problems by general practitioners. AB - The majority of people in the community who have a psychiatric disorder will consult their general practitioner. Referrals from general practice to specialist services are, however, relatively rare. The filter between primary care and specialist care has been characterized by Goldberg and Huxley as the least permeable of the filters separating psychiatrists and other specialists from the populations they serve. These referrals form the subject of this study in the Netherlands. Using a large database of doctor-patient contacts, the proportion of mental health disorders resulting in a referral and the characteristics of the patient and general practitioner that are involved in such a referral have been determined. In addition, the type of mental health institution or specialist to which referrals were directed and the characteristics influencing this choice were examined. Only 6% of patients presenting with a psychiatric disorder during surgery hours were referred to specialist care. Younger patients, male patients and patients with severe diagnoses had a greater probability of being referred. The percentage of patients referred was higher in urban areas than in rural areas. Doctors with a limited task perception regarding mental treatment tended to refer more often. Although the diagnosis did have some relationship with the institutions to which patients were referred (psychotic conditions to psychiatric services and social/material problems to social workers), the most prevalent diagnoses (neurotic conditions and relationship problems) seemed to be more or less randomly distributed over the various possibilities. Preferences appeared to be related to the existence of regular meetings between general practitioners and specialists and a positive evaluation by general practitioners of the institution concerned. PMID- 8347389 TI - Continuing education for general practice. 1. Experience, competence and the media of self-directed learning for established general practitioners. AB - The arrangements under which continuing education for general practice is provided and attendance by general practitioners is rewarded have now been in operation for three years. More recently, reaccreditation has emerged as a significant issue for the profession. For these reasons it appears timely to review the whole basis of ongoing learning by established general practitioners. In this the first of two papers, learning by established professionals is considered in relation to the educational development of the learner, the role of experience and the goals of competence and performance. It is concluded that self directed learning based on experience should form the centre-piece of continuing education for general practice and that educational provision should adopt a complementary role in sustaining motivation to learn and by enabling learning from experience to be shared and enriched. A model of self-directed learning, connecting experience and competence through systematic application of three learning media, reading, reflection and audit, is proposed and related to appropriate educational participation by established general practitioners. PMID- 8347390 TI - Systematic care of diabetic patients. PMID- 8347391 TI - Heroin users on a methadone programme. PMID- 8347392 TI - Unrecognized ovarian failure after hysterectomy. PMID- 8347393 TI - Limited sequence divergence of HTLV-I of Indian HAM/TSP patients from a prototype Japanese isolate. AB - Nucleotide sequences of two HTLV-I proviruses isolated from Indian patients with HAM/TSP were analyzed. The sequence data of the env, pX, and LTR regions showed 98-99% homologies with the prototype HTLV-I, ATK-1, isolated from a Japanese ATL patient, indicating that HTLV-I isolates in India and Japan are similar, with minor variations. However, certain small sequences of noncoding regions in the pX and LTR showed differences of 6.1 and 7.2%, respectively, thus the conclusion could vary depending on the regions and length of the sequences used for comparison. PMID- 8347394 TI - HTLV-I-associated myelopathy in south India. PMID- 8347395 TI - The prevalence of antibodies to the human T lymphotropic virus (HTLV) in Ghana, West Africa. AB - We conducted a population-based serosurvey of urban areas and rural regions of southern Ghana, West Africa. Subjects (3763) of all ages were enrolled from 25 city and village sites and in studies of groups of special interest. "Positive" results were difficult to define because of a high frequency of results that were indeterminate on immunoblotting, the current standard for confirmation of HTLV-I. However, polymerase chain reaction results and HTLV type-specific discriminatory tests proved HTLV-I was present in Ghana. No HTLV-2 positivity was observed. By using strict criteria that considered indeterminate results as negative, the overall prevalence was found to be between 1 and 2% in all areas, with no difference by geographic location. Prevalence rose with age and was higher in adult women than men. However, in substudies of selected populations, we found HTLV prevalence among 124 persons with lymphomas and hematological malignancies was not different from that in the general population. Furthermore, the prevalence in prostitutes was similar to that in the general population and in pregnant women. HTLV-I is present in West Africa, but we were unable to associate HTLV-I seropositivity with malignancy or with prostitution. PMID- 8347396 TI - HIV-1 infection stimulates T cell invasiveness and synthesis of the 92-kDa type IV collagenase. AB - Tissue-specific localization of HIV-1-infected lymphoid cells may contribute to clinical manifestations of AIDS. Therefore we investigated the effect of HIV-1 infection on mechanisms of T lymphocyte invasion, a process required for movement of cells into and out of the circulation. In the present study, we demonstrate that HIV-1-infected human lymphocytes secrete increased amounts of the human 92 kDa type IV collagenase when compared to uninfected lymphocytes. Furthermore, HIV 1-infected lymphocytes degrade the extracellular matrix proteins collagen IV and fibronectin, and they are more invasive through a reconstituted basement membrane when compared to uninfected cells. The addition of either antibody to the 92-kDa collagenase or TIMP-2, a type IV collagenase inhibitor, abolishes invasive activity. These data suggest that HIV-1-infected lymphocytes express phenotypic characteristics that are consistent with an enhanced ability to leave the circulation and to localize in target tissues. Local viral infection or the release of viral proteins, cytokines, or proteolytic enzymes in tissues may contribute to pathogenesis. PMID- 8347397 TI - Adaptation of two primary human immunodeficiency virus type 1 isolates to growth in transformed T cell lines correlates with alterations in the responses of their envelope glycoproteins to soluble CD4. AB - Two sCD4-resistant, primary viruses (P-08 and P-17) were compared with two sCD4 sensitive, T cell line-adapted variants (C-08 and C-17) for their biochemical responses to sCD4. At 37 degrees C, neither primary virus shed gp120 within 8 hr at sCD4 concentrations of up to 500 nM, whereas C-08 and C-17 lost gp120 within minutes of addition of 5-10 nM sCD4. At 4 degrees C, however, P-17 and C-17 shed gp120 at similar rates in response to the same sCD4 concentration. Irrespective of the temperature, gp120 dissociation from both P-17 and C-17 was inhibited by CD4 MAbs 6H10 and 5A8, the latter of which blocks events subsequent to sCD4 binding. Binding of sCD4 to P-17 was greater at 4 degrees C than at 37 degrees C, whereas the converse was found for C-17. Consistent with this, P-17 was neutralized much more potently by sCD4 at 4 degrees C than at 37 degrees C, whereas C-17 was slightly more sensitive to sCD4 at 37 degrees C than at 4 degrees C. Resistance to neutralization by sCD4 is probably determined by kinetic parameters. We suggest that the acquisition of sCD4 neutralization sensitivity and the above biochemical responses to sCD4 are coincidental to the process by which some primary viruses adapt to growth in transformed T cells. Sequence data indicate that there are a limited number of amino acid differences between the Env glycoproteins of the primary viruses and their T cell line-adapted counterparts; the significance of the individual changes is under investigation, but both pairs of viruses have amino acid substitutions in a region of gp41 thought to contact gp120. PMID- 8347399 TI - Glucocorticoids synergize with tumor necrosis factor alpha in the induction of HIV expression from a chronically infected promonocytic cell line. AB - In this study we have investigated the effects of glucocorticoids (GCs) on the expression of human immunodeficiency virus (HIV) in a chronically infected promonocytic cell line, U1. Although no increase in virus production was observed in U1 cells stimulated with physiological concentrations of GC alone, costimulation with dexamethasone plus tumor necrosis factor alpha (TNF-alpha) synergistically enhanced TNF-alpha-dependent HIV expression. Molecular analysis demonstrated that GCs plus TNF-alpha resulted in an accumulation of steady state HIV RNA secondary to either an increase in transcription or an increase in message stability. These findings may be of physiological relevance because GCs are used in the treatment of certain disorders associated with HIV infection and TNF-alpha levels have been reported to be elevated in the plasma and cerebrospinal fluid of certain HIV-infected individuals. PMID- 8347400 TI - Kaposi's sarcoma in an Indian woman infected with HIV-1 and HIV-2. PMID- 8347401 TI - Physiologic effects of maternal smoking on breast-feeding infants. AB - Women who smoke and breast-feed pose an unknown threat to their infants' health. In this pilot study, relationships between ingestion of nicotine in breast milk and physiologic effects in the infant were investigated. Infant physiologic effects measured were temperature, pulse, respiration, systolic blood pressure, and oxygen saturation. Five smoking and five nonsmoking mother-infant pairs were studied. Breast milk was analyzed for nicotine using gas chromatography. Breast milk from smoking mothers contained a mean of 33.1 ng/mL of nicotine while the breast milk from nonsmoking mothers contained a mean of less than 6.45 ng/mL of nicotine. Infant physiologic measures were taken before and 20 min after breast feeding. After breast-feeding, infants of smoking mothers had a significant change in respirations and oxygen saturation while infants of nonsmoking mothers had a significant change in pulse only. Results provide a scientific basis for counseling smoking, breast-feeding mothers. PMID- 8347398 TI - Biological cloning of functionally diverse quasispecies of HIV-1. AB - Twenty putative clones of HIV-1, derived by biological cloning from two different individuals, were characterized in vitro for functional activity and genotypic diversity. Many of the biological clones isolated by this method were genetically distinct, and could be further distinguished by differences in replication kinetics, host cell range, and/or cytopathicity. Our findings indicate that biological cloning by limiting dilution cultures is an effective method for isolating replication-competent, functionally diverse quasispecies of HIV-1. PMID- 8347403 TI - Health care delivery to farmworkers in the Southwest: an innovative nursing clinic. AB - The migrant and seasonal farmworkers of the United States constitute a medically underserved population with many health care needs. Barriers to health care among farmworker families include financial constraints, cultural factors, restrictive labor practices, and absence of accessible clinics in rural areas. The Migrant Health Outreach Program is a federally funded mobile nursing clinic created to deliver health care to farmworkers where they live and work. The Migrant Health Outreach Team, composed of family nurse practitioners, registered nurses, and health care workers, offers primary care including health care maintenance and treatment of acute and chronic illness. The mobile nursing clinic serves the target population of farmworkers as a successful alternative to a traditional medical clinic. PMID- 8347402 TI - Physical health measurement of the older adult: new instrumentation. AB - The Georgia Centenarian Study examines the biologic, psychologic, and social factors contributing to life satisfaction and successful aging in late adulthood. Three age groups are included, 60 through 69 years, 80 through 89 years, and 100+ years. While the overall theoretical model includes multiple variables, physical health is viewed as critical to successful aging. This article presents an overview of physical health measurement for older persons. Some existing measures of physical health are included in the test battery for the Georgia Centenarian Study; however, the investigators determined the need for the inclusion of a new instrument. This article describes existing measures as well as the rationale and process of development of a new instrument. PMID- 8347404 TI - Facilitating the nurse practitioner's research role: using a microcomputer for data entry in clinical settings. AB - Data coding and entry can be a tedious and error-prone component of research. Statistical packages for a microcomputer are now available that enable the researcher to create data entry forms in a spread sheet format. In this article the use of software that can be used for data entry, manipulation, and analysis is discussed. In a practice setting these features are particularly useful, because the nurse practitioner can take the microcomputer to the clinical facility and enter data directly from client-provider interactions or from records. In clinical settings where client data are entered directly into a computer database as part of assessment and care giving, data can be downloaded onto this or similar programs for manipulation and analysis. PMID- 8347405 TI - Use of clozapine in primary care. AB - While clozapine represents a revolutionary advance in the treatment of schizophrenia, it carries with it a formidable side-effect profile. Agranulocytosis may indeed be life-threatening to a small number of patients. The nurse practitioner must be aware of this and other side effects in order to competently care for patients with psychiatric problems. It is also essential that there be a collaborative relationship between the nurse practitioner and a mental health provider. Only through appropriate consultation and referral will the needs of psychiatric patients be met in a timely and comprehensive manner. PMID- 8347406 TI - ERISA: a little discussed but formidable barrier to health care reform. Employment Retirement Income Security Act. PMID- 8347407 TI - Distinguishing between licensure proceedings and malpractice suits. PMID- 8347408 TI - 'Is half the profession apathetic to further learning?'. PMID- 8347409 TI - 'Images of your future'. PMID- 8347410 TI - The location of a disposable broken bur in the tongue. PMID- 8347411 TI - A retrospective study comparing duplication and conventionally made complete dentures for a group of elderly people. AB - The duplication technique is a well recognised method of replacing complete dentures. Advantages claimed for this technique are that patients adapt more easily to their new complete dentures and the numbers of treatment visits are reduced. The case notes of 100 patients were examined retrospectively, 50 of whom had had dentures constructed by undergraduates using a duplication technique and 50 with a conventional technique. In addition, a questionnaire was sent to the patients to obtain their views on the replacement dentures. The 'duplication group' required fewer visits for the delivery of the dentures, but there was no statistical difference between the numbers of post-insertion visits, for the two groups, needed to make the dentures comfortable. The only identifiable reason for selecting a duplication technique was the failure of construction of new dentures by a conventional method in 15 patients. Apart from this the two groups appeared remarkably similar when comparing age of dentures being replaced, period of edentulousness, number of previous complete dentures and medical histories. As judged by the questionnaire more patients in the duplication group continued to wear their new dentures compared to the conventional group. PMID- 8347412 TI - The future role of dental therapists in the UK: a survey of District Dental Officers and General Practitioners in England and Wales. AB - A postal questionnaire concerning the opinion of the dental profession as to the future role of dental therapists in the UK was sent to a random sample of 30 District Dental Officers and 70 General Dental Practitioners. In total 76 questionnaires were returned, 26 from DDOs, 50 from GDPs, giving corrected response rates of 86.7% and 57.1% respectively. Returns revealed that 69.2% of District Dental Officers predicted a future role for dental therapists in the Community Dental Service. A total of 47.5% of General Dental Practitioners stated they would like to see therapists working in general dental practice, with 40% of this group willing to employ a therapist providing the current legislation was changed. The most popular predicted role in both services appears to be an equal division between the provision of clinical care and dental health education. Recently qualified General Dental Practitioners were more in favour of the employment of therapists than older members of the profession, which suggest that with time, the demand for this auxiliary in general dental practice could increase. PMID- 8347413 TI - Allergic contact dermatitis associated with the use of an Interlandi headgear in a patient with a history of atopy. AB - An allergic contact dermatitis (ACD) reaction associated with the use of an orthodontic headgear is described in a patient with a history of atopy. The problems relating to the differential diagnosis between these two conditions are discussed. This case highlights that during medical history taking specific questioning relating to nickel sensitivity should be undertaken to identify those patients who may be at risk. PMID- 8347414 TI - Facial sinus formation secondary to a parotid duct calculus. AB - A case of facial sinus formation secondary to calculus obstruction of the parotid duct is reported. The aetiology and management of this condition are discussed. PMID- 8347415 TI - Stasis dermatitis: practical pearls for the dermatologic nurse. AB - Stasis dermatitis is a common, chronic skin condition. Treatment requires attention to local skin-care measures, systemic factors contributing to pedal edema, and surgical/mechanical approaches to promote venous outflow and decrease pooling. Compliance problems can result when patients have a poor understanding of their treatment program, have anxiety regarding costs, or experience the discomfort associated with therapy. Understanding the pathophysiology of stasis dermatitis, and treatment options with emphasis on practical treatment can improve patient compliance. PMID- 8347416 TI - What's your assessment? Candidiasis. PMID- 8347417 TI - Skin care: burn survivor case study. Part 2. AB - A clinical methodology involving consultation, assessment, planning, implementation, and evaluation is important in meeting patients' skin care and cosmetic needs. Part Two of this three-part series examines how this systematic and practical approach was used in improving a burn survivor's skin quality. PMID- 8347419 TI - Personal appearance overlooked in wound care. PMID- 8347418 TI - Nursing perspectives: aseptic techniques in wound care. AB - The availability and use of gloves and antibiotics contribute to a false sense of security in providing wound care. The significance of nurses' attention to the principles of aseptic technique need to be re-established in nursing practice. PMID- 8347420 TI - Plasma membrane p180, which insulin receptor phosphorylates in vivo, is not a tyrosine kinase. AB - The earliest substrates to the transmembrane insulin receptor tyrosine kinase, that would function in insulin signalling, are likely to be associated with the plasma membrane. Rat liver plasma membrane 180,000 M(r) protein (p180) is a substrate to the insulin receptor in vitro [Goren et al. (1990) Cellular Signalling 2, 537-555]. The question as to whether p180 is a substrate in vivo was addressed. Half ml 0.9% NaCl or 500 micrograms insulin was injected into rat livers. Purified plasma membrane glycoproteins from the livers were assayed for in vitro phosphorylation reaction products and endogenous tyrosine-phosphorylated proteins. Membranes from insulin-injected rat livers contained phosphorylated p180 and phosphorylated insulin receptor beta-subunit, whereas saline-injected rat liver membranes contained neither. These data suggested that p180 is an in vivo substrate to the insulin receptor. In vitro p180 is tyrosine-phosphorylated in the absence of insulin. p180, therefore, may be the epidermal growth factor (EGF) receptor or another tyrosine kinase that could be part of a phosphorylation cascade initiated by insulin. Two different experiments suggested that p180 is not the EGF receptor: (i) two-dimensional gel electrophoresis (first dimension- non-equilibrium pH-gradient gel electrophoresis) indicated that p180 is a more basic glycoprotein than EGF receptor; and (ii) based on reverse-phase high pressure liquid chromatography, the tryptic-phosphopeptides of carboxymethyl Sepharose-purified phosphorylated-p180 were different from those of A431 cell phosphorylated-EGF receptor. Similarly, two different experiments demonstrated that p180 is not a tyrosine kinase: (i) gel-permeation chromatography separated the insulin receptor from p180 and only insulin receptor was autophosphorylated in vitro; and (ii) membrane proteins not bound to immobilized ATP contained p180. Thus, p180 can associate with the insulin receptor and be phosphorylated in vitro and in vivo; however, p180 does not function in an insulin receptor-mediated phosphorylation cascade. PMID- 8347421 TI - GTP[S] stimulates migration of electropermeabilized neutrophils via a pertussis toxin-sensitive G-protein. AB - Electropermeabilized neutrophils were used to study the role of G-proteins in neutrophil migration. Rabbit neutrophils, under specific conditions, retained their ability to migrate after electropermeabilization. Introduction of guanosine 5'-[3-thio] triphosphate (GTP[S]) into the cell interior stimulated random migration and enhanced migration activated by a suboptimal concentration of formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) (10(-11) M). GTP[S] had no effect on random migration by intact cells, or on migration of intact cells activated with a suboptimal concentration of fMet-Leu-Phe, indicating that the effect of GTP[S] was intracellular. The effects of GTP[S] were inhibited by pertussis toxin and by guanosine-5'-[2-thio] diphosphate (GDP beta S) indicating that a pertussis toxin-sensitive G-protein was involved. GTP stimulated random migration to the same extent as GTP[S], but had only a small effect on migration activated by a suboptimal concentration of fMet-Leu-Phe (10(-11) M). Several other nucleotides tested had no effect on random migration or migration activated with 10(-11) M fMet-Leu-Phe. The results show that neutrophil migration can be potentiated by direct activation of a pertussis toxin-sensitive G-protein, and the results obtained with GTP suggest that possibly more than one G-protein is involved in this process. PMID- 8347423 TI - Workshop on risk assessment of human exposure to pathogenic micro-organisms. National Institute of Public Health & Environmental Protection. Bilthoven, The Netherlands. PMID- 8347424 TI - Use of microbial risk assessment in setting US drinking water standards. PMID- 8347422 TI - Activation of phospholipase D following perturbation of the human T lymphocyte antigen receptor/CD3 complex is dependent upon protein kinase C. AB - Perturbation of the T lymphocyte antigen receptor/CD3 complex or phorbol ester stimulation leads to activation of phospholipase D in the Jurkat T lymphocyte cell line. These observations suggested that phospholipase D activation might result from activation of protein kinase C. In other systems, phospholipase D activity has been shown to be under G-protein or protein kinase C control. Studies detailed here demonstrate that commonly used inhibitors of protein kinase C had unrelated, diverse effects on phospholipase D activity in T lymphocytes. However, protein kinase C down-regulation resulting from prolonged cellular exposure to phorbol esters led to abrogation of anti-CD3-stimulated phospholipase D activation. The results presented underline the complexity of studies employing inhibitors of protein kinase C, suggest interesting approaches to isolation of phospholipase D dependent signalling pathways, confirm that T cell antigen receptor-linked activation of phospholipase D is dependent upon protein kinase C activity and suggest that distant events of T lymphocyte activation are dependent upon the establishment of a positive feedback loop involving protein kinase C and phospholipase D which would result in the prolonged activation of protein kinase C required for certain lymphokine production. PMID- 8347425 TI - Fumonisins. AB - Fusarium moniliforme Sheldon is a common fungal contaminant of corn and produces a variety of mycotoxins. Among these are the recently discovered fumonisins, which are now known to cause certain animal diseases, namely leukoencephalomalacia in horses and pulmonary edema in swine. There is a significant association between their presence in corn and human esophageal cancer in southern Africa. Fumonisin B1 causes liver cancer in rats. Five other fumonisins--B2, B3, B4, A1 and A2, have been isolated; the last two are N acetates of fumonisins B1 and B2 and do not appear to be toxic. Several other Fusarium species are now known to produce fumonisins. Procedures for detection and determination of fumonisins include thin layer chromatography, liquid chromatography (with fluorescence derivatization), post-hydrolysis gas chromatography, immunochemical assay, and mass spectrometry. In addition to their natural occurrence in corn-based animal feeds and in home-grown African corn used for food, fumonisins are frequently found in commercial corn-based foods. Fumonisins are moderately heat-stable. No effective detoxification process has yet been developed for use with fumonisin-contaminated feeds. PMID- 8347426 TI - Heat and acid sensitivity of motile Aeromonas: a comparison with other food poisoning bacteria. AB - The present study was undertaken to compare the heat and acid sensitivity of aeromonads with those of other food-poisoning bacteria. It became obvious that aeromonads were more sensitive to heat than Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella typhimurium. Aeromonads were killed in peptone water within 2 min at 55 degrees C, while the other bacteria survived heating at 55 degrees C for more than 15 min. Aeromonas cells were also less resistant to heat in hamburger steaks. These findings suggest that Aeromonas infection can easily be prevented by heat treatment, although correct handling of food is required to avoid recontamination since aeromonads are very common in various kinds of food. E. coli, S. aureus and S. typhimurium cells survived in buffer at pH 3.2 and in foods seasoned with vinegar. By contrast, Aeromonas cells were found to be highly sensitive to acid. However, the resistance of Aeromonas to acid may be sufficient to allow it to infect the gastrointestinal tract since Vibrio parahaemolyticus, which causes numerous outbreaks of food-poisoning every year in Japan, was susceptible to acid to the same extent as Aeromonas. PMID- 8347427 TI - Characterization and frequency distribution of species of lactic acid bacteria involved in the processing of mawe, a fermented maize dough from Benin. AB - Lactic acid bacteria involved in the natural fermentation of both home-produced and commercial mawe were investigated during a 72 h fermentation period. Lactobacillus spp. constitute the majority (94%) of the strains of the lactic acid bacteria isolated, among which 89% represent the Betabacterium group. They include L. fermentum (biotype cellobiosus) (41%), L. fermentum or L. reuteri (19%), L. brevis (26%), L. confusus (less than 2%), L. curvatus (less than 1%) and L. buchneri (less than 1%). Other isolated lactic acid bacteria were L. salivarius, Lactococcus lactis, Pediococcus pentosaceus, Pediococcus acidilactici and Leuconostoc mesenteroides. Several species were detected at the early stage of fermentation, but the final stage was dominated by L. fermentum (biotype cellobiosus) and L. fermentum or L. reuteri totalling 90% of the isolated strains. The trend was the same for both home-produced and commercial mawe. No strains of L. plantarum, generally reported as dominating lactic acid bacteria at the final stage of fermentation of most plant foods, were isolated. PMID- 8347428 TI - Distribution of Listeria spp. in confectioners' pastries from western France: comparison of enrichment methods. AB - Three hundred samples of pastry from 100 different suppliers in western France, including butter-cream, whipped dairy cream and custard filled cakes from each supplier, were collected and tested for the occurrence of Listeria spp. in 25 g samples. Listeria spp. were detected in 21.7% of he samples: Listeria monocytogenes in 13.7%, Listeria innocua in 10% and Listeria seeligeri in 2.3%. Thirteen samples were contaminated with two species simultaneously. The frequency of contaminated samples was not related to the composition of the pastry filling used, but it seemed to increase with the number of aerobic contaminant microorganisms in the dairy cream-based samples. The contamination rate was dependent on the place of manufacture. The numbers of Listeria spp. and Listeria monocytogenes were estimated on positive samples at the 25 g level as follows: < 0.3/g, Listeria spp. in 47 samples, L monocytogenes in 27; 0.3-30/g, Listeria spp. in 13, L. monocytogenes in nine; 30-300/g, L. monocytogenes in one; 300 3000/g; L. monocytogenes in three; 700,000/g, L. monocytogenes in one. Various detection methods were tested, including two enrichments broths tested in parallel: a modified LEB broth using 10 mg/l acriflavine-HCl and the UVM 1 broth, with incubation at 30 degrees C and streaking onto PALCAM agar. The enrichment procedures were: (a) primary enrichment of 25 g sample and plating after 48 h and 7 days; (b) secondary enrichment by subculturing the primary enrichment broths incubated for 24 h and 6 days, into fresh enrichment broth, then plating after 24 h incubation; (c) pre-enrichment of 25 g sample for 24 h in the basal enrichment broths without inhibitors, followed by subculturing in complete broths which were plated after 24 h and 6 days incubation. In all cases, UVM performed better than the LEB broth. It was unnecessary to extend the primary enrichment period beyond 48 h. Secondary enrichments inoculated from 24-h incubated primary enrichments gave a slightly better isolation rate than primary enrichments. Secondary enrichments made from 6-day incubated primary enrichments gave no additional advantage. The pre-enrichment procedure had an efficiency higher than that obtained by primary enrichment. PMID- 8347429 TI - Characteristics and antagonistic activity of lactic acid bacteria isolated from chilled fish products. AB - In fish products, contrary to other foods, the commercial use of starter cultures is relatively unexploited. In this study, 61 isolates of lactic acid bacteria from lightly preserved, chilled fish products were characterized with special emphasis on their antagonistic activity and their possible use as starter cultures. The strains were phenotypically identified and characterized with regard to gas production, carbohydrate fermentations, production of off odours, H2O2-production, antagonistic activity and growth at 2, 5 and 10 degrees C. Growth at 10 degrees C was detected for all strains within 4 days. At 5 degrees C, 90% of the isolates were growing within 3-9 days. At 2 degrees C only 33% of the strains were growing within 9 days. Fourteen strains were selected for further testing of antagonistic activity against spoilage- and pathogenic bacteria at different pH in a disc assay. Two strains, a Leuconostoc spp. (V 6) and a Lactobacillus plantarum (LKE 5), differed from the other lactic acid bacteria by a very wide inhibitory spectrum for V 6 and by very distinct inhibition zones for LKE 5. The mechanisms of their inhibitory effects are discussed. PMID- 8347430 TI - Changes in the microflora on commercial beef trimmings during their collection, distribution and preparation for retail sale as ground beef. AB - A commercial process for ground meat production, from the collection of meat plant trimmings to the retailing of consumer packs of ground beef, was examined. The selected process compiled with current concepts of Good Manufacturing Practice. During storage for up to 18 days before grinding, most trimming developed a flora of lactobacilli, of up to 10(7) CFU/g. Numbers of coliforms and of Escherichia coli on stored trimmings increased little and not at all, respectively. Increased total counts, and numbers of both coliforms and E. coli in displayed product indicated loss of control of the temperature of the displayed packaged product. It appears that the need to store a product, taking into account the unpredictable fluctuations in supply and demand, will inevitably result in much ground beef carrying large numbers of spoilage bacteria. Furthermore, currently accepted Good Practice in the retail handling of ground beef does not adequately control either spoilage or the growth of pathogenic bacteria. PMID- 8347431 TI - Presence of Listeria monocytogenes, motile aeromonads and Yersinia enterocolitica in environmental samples taken from a supermarket delicatessen. AB - Environmental swab samples collected on three occasions from a supermarket delicatessen were examined for the presence of Listeria monocytogenes, motile aeromonads and Yersinia enterocolitica. Strains of Y. enterocolitica belonging to a pathogenic biotype were not recovered, but isolates of L. monocytogenes and motile aeromonads were found. Contaminated surfaces and items that came into direct contact with ready-to-eat food included a slicing machine, a knife and parsley that was to be used as a garnish. Most sites sampled near a display of processed meats requiring cooking, such as bacon and sausages, yielded positive results and could therefore act as a source of cross contamination for ready-to eat meats. PMID- 8347432 TI - Occurrence of Aeromonas spp. in samples of ground meat and chicken. AB - Aeromonas spp. was commonly isolated from ground meat and chicken samples at the retail level. The dominant species in ground meat were A. hydrophila and A. caviae. In chicken, A. sobria was common while A. caviae was isolated infrequently. Although A. hydrophila was isolated from 75% of ground meat samples and 62% of chicken samples, DL-lactate-positive A. hydrophila (genospecies 1) was isolated from only 25 or 37% or respective samples. Sorbitol-positive A. hydrophila (genospecies 3) was common in both ground meat and chicken. PMID- 8347433 TI - Local pharmacotherapy for impotence. PMID- 8347434 TI - Talking heads: a combined assault on atheroma. PMID- 8347435 TI - Hypothyroidism in the elderly: clinical assessment versus routine screening. AB - A total of 304 patients aged 65 years or over were prospectively studied over a four-month period to assess whether clinical findings or routine screening were more helpful in diagnosing biochemical hypothyroidism. The most useful symptom relevant to a possible diagnosis of hypothyroidism in the elderly was found to be dry skin. Dermatological signs and certain ECG abnormalities (especially atrial fibrillation) were helpful when querying a diagnosis of hypothyroidism. Almost 50% of patients receiving amiodarone had abnormal thyroid function tests (TFTs). Routine screening for hypothyroidism does not seem justifiable from our available data although this conclusion may have been different had hospital clinicians and general practitioners followed their patients up more closely after an initial abnormal result was obtained. PMID- 8347436 TI - An integrated haematuria clinic. AB - The prognosis of bladder cancer is worsened by delay in its management. To reduce such delay we have organised a clinic where intravenous urography and cystoscopy, using a flexible cystoscope, are carried out at the patient's first visit. In a two-year period 321 patients attended this clinic. The results of investigation in 305 patients are reported. A total of 6% of patients with microscopic haematuria (n = 52) and 15% of patients with macroscopic haematuria (n = 253) had transitional cell carcinomata. This difference was not significant (P = 0.08, chi squared). The delay between referral and trans-urethral resection of tumour for patients with bladder tumours was reduced from a mean of 60 days to a mean of 33 days by the institution of the clinic (P < 0.01, Mann-Whitney). We recommend that all patients referred to a urological service with haematuria, whether macroscopic or microscopic, should be investigated. The integration of that investigation in a single day decreases delays in diagnosis and management. PMID- 8347437 TI - The efficacy and sedative profile of astemizole and cetirizine in the treatment of grass pollen hayfever in general practice. AB - The antihistamines astemizole and cetirizine were compared for the treatment of grass pollen hayfever in 158 patients who received either astemizole (10 mg od) or cetirizine (10 mg od) for a four week period in a randomised double-blind, double-dummy, parallel group, comparative assessment. Patients visited their general practitioner (GP) on three occasions and at each visit the GP made an assessment of the severity of individual hayfever symptoms. Patients recorded daily throughout the study the severity of their hayfever symptoms and their level of daytime sedation on visual analogue scales in a diary card. The primary measure of efficacy was the overall symptom visual analogue scores recorded daily by the patients. The results demonstrate that these two antihistamines are equally effective treatments for hayfever, in terms of magnitude of symptom relief, speed of onset of symptom improvement and lack of sedative effect. PMID- 8347438 TI - The outcome of surgery of aneurysmal subarachnoid haemorrhage. AB - Aneurysmal subarachnoid haemorrhage is a challenging pathology which remains a cause of considerable mortality and morbidity. To demonstrate to general practitioners the results of surgery for this condition a retrospective study of 160 consecutive cases who had undergone aneurysmal surgery was carried out. On admission 57% of cases had a good Hunt and Hess grade (grades I and II) and 43% a poor grade (grades III, IV and V). Twelve per cent of cases had a pre-existing hypertension and 73% of cases were treated with nimodipine. Angiography was performed from 0 to 73 days (median 3 days) after the bleed. Early surgery (within the first three days after the bleed) was performed in 41% of cases. Twenty-two per cent of cases rebled before surgery from 1 to 69 days after initial presentation (median seven days). Delayed cerebral ischaemia was diagnosed in 38% of cases, but only 15% of cases had evidence of low density on the CT scan. The outcome was determined at six months using the 'Glasgow outcome scale'. Fifty-five per cent of cases made a good recovery (back to normality), 15% a fair recovery (moderately disabled but independent), 15% a poor recovery (severely disabled and dependent), and 15% died. The significant poor prognostic factors were: a poor pre-operative Hunt and Hess grade, the presence of an intracerebral haematoma or angiographic spasm, evidence of rebleeding and early surgery without treatment with nimodipine. Other factors which did not reach a statistical significance include: age, presence of subarachnoid and intraventricular blood on CT, timing of surgery, history of long-standing hypertension, intraoperative rupture, and the development of hydrocephalus or delayed ischaemia. PMID- 8347439 TI - Acarosan and the Acarex test in the control of house dust mite allergens in the home. AB - House dust mites are believed to be major triggers for allergic disease in atopic individuals. As part of a programme controlling dietary and aero-allergen exposure in high-risk infants, an acaricidal foam and powder (Acarosan) was applied to bedroom and main living room carpets, as well as upholstered furniture, on four occasions in the first year of life. Dust was assayed for mite antigen (Der p1) and these results compared with the semi-quantitative assay of guanine content (Acarex Test). After nine months mean Der p1 levels had decreased by 70% in the treatment group. Proportionally, the greatest fall occurred in those items that had the highest initial mite antigen content. The Acarex score does show a correlation with Der p1 levels, but cannot replace antigen assay when accurate data is required. A chemical acaricide may help reduce house dust mite antigen levels, but is not by itself sufficient to reduce levels below that considered critical for sensitisation. PMID- 8347440 TI - A survey of aspirin use in the pre-hospital treatment of suspected acute cardiac chest pain. AB - Recent large studies have demonstrated the value of early intervention with aspirin and thrombolysis in myocardial infarction for patients reaching hospital alive. Management of patients with suspected myocardial infarction prior to hospitalisation is an important area of acute cardiac care. Guidelines for good practice suggest the early administration of aspirin should be considered when an infarct seems likely. We have found aspirin less commonly used than other interventions prior to hospital admission in patients with suspected acute cardiac pain. PMID- 8347441 TI - Is there any relationship between pica and liver failure? AB - Pica is defined as the compulsive eating of anything and has been known for more than a hundred years. It is a worldwide problem which can be seen in every race, age, sex and geographic region. Its true incidence is not known and may be greater than expected. Although it is a widespread phenomenon, the causes and risk factors of pica are not well established. Clinical signs and symptoms of pica syndrome are numerous but liver disorder associated with this syndrome is not widely reported. We reported here liver disorder possibly related with pica. PMID- 8347442 TI - Potassium channel activators in the management of ischaemic heart disease: a focus on nicorandil. AB - The treatment of angina pectoris continues to pose challenges. Novel new compounds are a rarity, but the potassium channel activators represent a new class of drugs with novel mechanisms of action. Nicorandil will be the first available potassium channel modulator for treatment of angina, and the following review assesses its clinical potential. PMID- 8347443 TI - The management of rectal bleeding. AB - Rectal bleeding is a common symptom in the general population; it may signal the presence of serious gastrointestinal disease but more frequently is caused by minor and self-limiting local ano-rectal conditions. Appropriate and accurate evaluation of rectal bleeding requires an investigative approach which balances an appreciation of the need to provide an adequate explanation for the bleeding against over-investigation, excessive referral and wasted resources. As doctors of first contact, general practitioners (GPs) are frequently faced with difficult questions concerning the optimum management of rectal bleeding. This paper was prepared as a result of a series of interactive meetings with over 1,000 GPs from throughout the UK, which revealed wide variations in the possession and use of investigative equipment in the surgery, access to secondary care facilities, estimates of the prevalence and potential seriousness of rectal bleeding and the management strategies adopted in response to a series of case histories. We highlight a number of unresolved issues about the roles of GPs and hospital specialists in the management of rectal bleeding and the need for research directed at answering outstanding questions. In addition, a management strategy is proposed which might form the basis for a protocol for care, shared between general practice and the hospital. PMID- 8347445 TI - An unusual presentation of bilateral tubal ectopic pregnancy. AB - The diagnosis of ectopic pregnancy is sometimes difficult on clinical grounds because of the varied presentation. The clinical triad of amenorrhoea, abnormal vaginal bleeding and lower abdominal pain often raises the suspicion of the diagnosis. There are, however, instances where one or other feature of the triad may be absent. PMID- 8347444 TI - Endometriosis--the problems of intestinal obstruction. AB - Endometriosis is a relatively common condition in women of child-bearing age, and coincidental intestinal serosal involvement is frequently recognised. However, intestinal obstruction, although reported, is rare. We report what we believe is the first case with synchronous ileo-caecal and rectosigmoid obstructing endometriomas. Endometriosis as a cause of bowel obstruction is discussed and in particular the differential diagnosis from Crohn's disease and malignancy. PMID- 8347446 TI - Pericardial effusion--an uncommon complication of Salmonella enteritis. AB - A 62-year-old lady who was receiving corticosteroids for rheumatoid arthritis was admitted suffering from dehydration due to salmonella enteritis. Despite rehydration and appropriate chemotherapy she remained unwell and developed hypotension and elevation of her jugular venous pressure. Echocardiography and subsequent aspiration demonstrated a purulent pericardial effusion from which S typhimurium was cultured. Following aspiration and a change of antibiotic therapy, her condition improved dramatically. PMID- 8347447 TI - Gallstone cirrhosis: are we only seeing the tip of the iceberg? AB - Gallstones are common and their incidence increases with age. Fifty per cent of these stones are in the common bile duct (CBD) in the elderly. Most of them are silent but with time there is an increasing chance of developing symptoms which are more likely to be serious in the elderly. Failure to relieve mechanical obstruction of bile flow may lead to secondary biliary cirrhosis. It has been estimated that on average secondary biliary cirrhosis develops some seven years after the onset of obstruction from a stricture, four and half years after gallstone obstruction and 10 months after the onset of malignant stricture. The characteristic features are the pathological findings of portal-portal linkages, with a pattern of monolobular cirrhosis and the preservation of normal vascular relationships. Secondary biliary cirrhosis may lead to hepatic insufficiency and portal hypertension with the resultant complications, such as bleeding oesophageal varices, hypersplenism with pancytopenia, ascites and encephalopathy. We describe a patient in whom the diagnosis was not suspected until laparotomy and confirmed only at autopsy. PMID- 8347449 TI - Periorbital necrotizing fasciitis: trivial facial injury resulting in cardiac arrest. AB - Facial injuries in the context of alcohol abuse are a common presentation to casualty departments. While the majority are self limiting, the presence of periorbital or facial oedema should alert physicians to the development of periorbital necrotizing fasciitis. Here, a case illustrates this unusual manifestation of streptococcal infection, and emphasises the rapid onset and devastating systemic and local cosmetic consequences of this condition. PMID- 8347448 TI - Severe large and small bowel fibrosis clinically mimicking gross splenomegaly. AB - The case of an 18-year-old female, with mild left hypochondrial pain and an abdominal mass mimicking gross splenomegaly, with severe small and large bowel fibrosis and adhesions and numerous mononuclear cellular infiltrate on histology, is presented. A clear picture of intestinal obstruction only unfolded terminally. She died within 48 hours of presentation. Our patient illustrates the fact that severe intestinal adhesions may present with very mild symptoms and signs and therefore a high index of suspicion is necessary, to reduce the attendant high mortality in intestinal obstruction in our environment. PMID- 8347450 TI - The neuroleptic malignant syndrome: a missed diagnosis? AB - The neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction to major tranquilizer drugs characterised by hyperpyrexia, extrapyramidal disorders and altered consciousness. First described in 1968 by Delay and Deniker, early case reports suggested a mortality of between 20 and 30%. Though the syndrome is now more widely recognised, the diversity of its clinical features may not always be appreciated and may lead to diagnostic confusion with other, more common, disorders. We report on two severe cases of NMS: in the first the diagnosis was initially thought to be sepsis from a urinary tract infection, and in the second the primary clinical diagnosis was of a mid brain infarction. PMID- 8347453 TI - Experimental allergic encephalomyelitis raises betaine levels in the spinal cord of strain 13 guinea-pigs. AB - Chronic relapsing experimental allergic encephalomyelitis, an animal model of multiple sclerosis, was induced in Strain 13 guinea-pigs by subcutaneous injection of spinal cord homogenate and Freund's incomplete adjuvant supplemented with Mycobacterium tuberculosis. High resolution 1H NMR spectra of CNS tissue extracts indicated that the levels of choline metabolites, particularly betaine, were elevated in the spinal cord tissue, the principal site of lesion formation in this guinea-pig strain. The spectra also show that N-acetylated compounds are slightly depleted in the disease. The results are discussed in relation to the biochemical interpretation of NMR spectra obtained in vivo from patients with multiple sclerosis. PMID- 8347452 TI - Esophageal cancer phospholipid characterization by 31P NMR. AB - Phospholipid extracts of surgical tissue specimens from 18 patients, consisting of normal esophagus, distal esophageal tumor and normal stomach, were analyzed using 31P NMR. The prominent phospholipids detected in these tissues included cardiolipin (CL), phosphatidylethanolamine plasmalogen, phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SPH), phosphatidylinositol (PI), phosphatidylcholine plasmalogen and phosphatidylcholine (PC). Very small quantities of the phospholipids lysophosphatidylcholine, phosphatidic acid, phosphatidylglycerol, and an uncharacterized phospholipid at -0.13 delta also were detected in some of the 54 tissue specimens analyzed. The mean relative concentrations of these phospholipids, in mole percentages of total detected phosphorus, were determined from the acquired spectra and used to differentiate among the three tissue groups. The relative concentrations of the following phospholipids differed significantly (p < 0.001) among the respective tissue groups: normal esophagus vs esophageal tumor, PS, SPH, PI, PC; normal esophagus vs normal stomach, CL, PE, PS, SPH; esophageal tumor vs normal stomach, CL, PE. Membrane phospholipids implicated in modulating the growth and metastases of tumors of epithelial origin can be profiled to discriminate among normal esophagus, distal esophageal tumor and normal stomach using 31P NMR. PMID- 8347454 TI - A selective inversion recovery method for the improvement of 23Na NMR spectral resolution in isolated perfused rat hearts. AB - Shift-reagent-aided 23Na NMR spectroscopy allows differentiation of the intracellular (Na(i)) and extracellular sodium (Na(o)) signals. The goal of the present study has been to develop a 23Na NMR spectroscopic method to minimize the intensity of the shift-reagent-shifted Na(o) signal and thus increase Na(i) resolution. This is achieved by a selective inversion recovery (SIR) method which enhances the resolution between the Na(i) and Na(o) peaks in shift-reagent-aided 23Na NMR spectroscopy. The application of SIR with Dy(TTHA), Tm(DOTP), or with low concentrations of Dy(PPP)2 results in both good spectral resolution and physiologically acceptable contractile function in the isolated, perfused rat heart model. PMID- 8347451 TI - Controllable graded cerebral ischaemia in the gerbil: studies of cerebral blood flow and energy metabolism by hydrogen clearance and 31P NMR spectroscopy. AB - A technique for remotely controlling the degree of carotid artery occlusion in the gerbil model of cerebral ischaemia has been developed. The technique relies on manually adjustable nylon snares around the carotid arteries, in conjunction with a computer-based monitoring system, to control the degree of occlusion. This has allowed us to determine the dependence of energy metabolism (as assessed by 31P NMR spectroscopy) on blood flow in greater detail than was possible in our previous studies. Data obtained show that energy changes first appear at flows of 25-30 mL/100 g/min, while at flows below 20 mL/100 g/min there is a major derangement of energy metabolism. The model was used to determine the sensitivity of cerebral energy metabolism to reduced cerebral blood flow under normothermic conditions and in mild hypothermia (30 degrees C). Hypothermia had a protective effect in that energy metabolites were maintained at flows significantly below the normothermic threshold. PMID- 8347456 TI - Use of computer simulations for quantitation of 31P ISIS MRS results. AB - The difficulties in quantitation of in vivo 31P spectra are exacerbated by the fact that, in general, coils with inhomogeneous B1 fields are used with in vivo samples. A general method for quantitation of in vivo 31P MRS results obtained with the ISIS localization method was developed using computer simulations. The simulation calculates the preparation of the sample magnetization throughout the sample by the ISIS pulse sequence, as well as the sensitivity of signal reception. The calculation accounts for both the B1 field and the B0 gradients applied to the sample. The sensitivity of the experiment is expressed by integration of the simulated signal over the sample, assuming a homogeneous sample. The primary advantage of this approach is that a separate localization experiment on a phantom of known concentration is not required each time parameters of the localization experiment, such as dimensions or location of the localized volume, are altered. In addition, the simulations indicate the degree of contamination (signal from outside of the localized volume) that occurs, and provide a means of comparing different executions of the ISIS experiment. Experiments were performed on phantoms to verify the simulations, and experimental results on human brain and liver are reproduced to show that this approach provides reasonable estimates of metabolite levels in terms of molar concentrations. PMID- 8347455 TI - The effect of oestrogen ablation on the phospholipid metabolite content of primary and transplanted rat mammary tumours. AB - The concentration of phospholipid metabolites was determined in chemical extracts from two types of rat mammary tumours and compared with proliferation data (S phase fraction). One of the tumours was an oestrogen-sensitive transplanted tumour. In this tumour the concentration of phosphocholine (PC) and glycerophosphorylcholine (GPC) correlated strongly with the S-phase fraction but not with the number of cells actively synthesizing DNA. Oestrogen ablation resulted in tumour regression. Regressing tumours contained less PC and more GPC than those actively growing. The other tumour was induced in rats by intravenous administration of N-methyl N-nitrosourea. Phosphoethanolamine (PE), PC and GPC levels were not associated with the S-phase fraction in this tumour. Oestrogen ablation resulted in tumour regression. There was no significant difference between the regressing and growing tumours in PE, PC or GPC content. PMID- 8347457 TI - A comparative study of 1H NMR lineshape fitting analyses and biochemical lipid analyses of the lipoprotein fractions VLDL, LDL and HDL, and total human blood plasma. AB - The purpose of this work was two-fold. In the first instance, 1H NMR spectra of the ultracentrifuged lipoprotein fractions (VLDL, LDL and HDL) from six volunteers with different clinical conditions were measured. The methylene regions of the experimental spectra were modelled in the frequency domain using non-linear lineshape fitting analyses. In this way the resolvable Lorentzian component structures of the methylene regions of these lipoprotein fraction spectra could be determined. Second, the lipoprotein fraction analyses were used to construct simplified component structures, which interpreted the lipoprotein fraction spectra well, and were feasible to use in the total plasma spectra analyses. The considerable overlap problem of the resonances was properly handled in this way. The NMR-based relative amounts of the lipoproteins (relative integrated intensities of the lipoprotein model signals) obtained were compared to the biochemically resolved relative molar percentages of the lipoprotein fractions and also of the lipid contents between the lipoprotein complexes. It was noticed that nearly all correlations were extremely good. Thus, it is suggested that the developed methodology could be used as a fast method to predict the relative amounts of the lipoproteins and also possibly the relative lipid contents between the major lipoprotein categories directly from the proton NMR spectrum of a total blood plasma sample. Furthermore, if internal or external reference for the integrated intensities of the proton NMR resonances were used, it should also be possible to obtain the absolute amounts of these quantities. PMID- 8347458 TI - Autoimmune disease and silicone breast implants. AB - An association between crystalline silica and immune disease has long been recognized. However, despite ongoing case reports of systemic autoimmune disease in silicone implant recipients, the available data has not been sufficient to prove or disprove a causal relationship. Silicone has been shown to "bleed" from the implants and can migrate to distant sites. There is evidence of cellular and humoral immune responses to silicone in vivo, but the role of these responses in the development of connective tissue disorders has not been determined. Further studies are necessary to elucidate the role of silicone, if any, in the pathogenesis of autoimmune connective tissue disease. Meanwhile, the implant population needs to be closely monitored; their clinical management should be based on a case by case evaluation. PMID- 8347459 TI - Clinical trials referral resource. Clinical trials using edatrexate. PMID- 8347461 TI - New MRI techniques effective in detecting implant leaks. PMID- 8347460 TI - Use of positron emission tomography in oncology. AB - Positron emission tomography is an imaging technique that produces images reflective of tissue biochemistry rather than anatomy. Utilizing different isotopes, many biochemical processes can be studied repetitively and non invasively in cancers in vivo. Malignant tissue is characterized by an accelerated rate of glycolysis. This biochemical characteristic of malignancy can be exploited by PET imaging with the radiopharmaceutical FDG. PET with FDG has been successful in imaging primary and metastatic cancer of the breast, colon, lung, head and neck, as well as sarcomas and lymphomas. PET FDG imaging has potential as a screening, diagnostic and staging tool in cancer. Recently, whole body PET techniques have been developed which permit imaging of the entire body during a single scanning session. PET also has tremendous potential as a cancer research tool to study serial estimates of tumor glycolysis, DNA turnover, oxygen metabolism, protein synthesis, and blood. PMID- 8347462 TI - Management of advanced cancers of the external nose. AB - Advanced carcinoma of the external nose is almost always associated with prior inadequate therapy. The first principle, therefore, in managing cutaneous malignancies of the nose is to achieve adequate tumor-free removal at the initial treatment. Recurrent carcinoma of the nose may require either hemirhinectomy or total rhinectomy to achieve tumor control. PMID- 8347463 TI - Screening mammography as public policy: who and how often? PMID- 8347464 TI - Management of supratentorial low-grade gliomas. AB - Low-grade gliomas are a clinically, radiographically, and pathologically diverse group of central nervous system neoplasms. Treatment decisions are based primarily on histologic tumor type and patient age. Pilocytic astrocytomas tend to occur in younger patients, are circumscribed, and amenable to cure with gross total resection. There is no role for the routine use of postoperative radiotherapy in these patients. In contrast, infiltrative tumors, including ordinary (nonpilocytic) astrocytomas, mixed oligoastrocytomas, and oligodendrogliomas occur in middle-aged patients and are generally not curable, even with gross total resection. Postoperative radiotherapy of these infiltrative tumors appears to improve survival, particularly in adults. Several ongoing clinical trials are addressing two issues: Observation vs radiotherapy and low dose vs high-dose radiotherapy in patients with ordinary astrocytomas, oligoastrocytomas, and mixed oligoastrocytomas. PMID- 8347465 TI - Induction of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in genetically resistant mice. AB - Theiler's murine encephalomyelitis virus-induced demyelinating disease, a murine model for multiple sclerosis, is the result of persistent infection which leads to a T cell-mediated immunopathology. Susceptible strains develop virus-specific DTH responses while resistant strains do not, and this response has been proposed as the basis for inflammation and demyelination. (C57BL/6 x DBA/2)F1 hybrid animals, normally resistant to TMEV-induced demyelinating disease, become susceptible when treated in vivo prior to infection with low dose cyclophosphamide. Comparable pretreatment of other resistant animals, C57BL/6 and CB6 (BALB/c x C57BL/6) F1 hybrids, does not render them susceptible (despite the H-2 identity of CB6F1 and B6D2F1 hybrids). Thus the "latent" susceptibility in B6D2F1 hybrids must be attributed to non-H-2 genes from the susceptible D2 parent. Resistance can be restored to CY-treated B6D2F1 animals by the adoptive transfer of splenic cells (including T cell enriched populations) from non-CY treated donors. Resistance to TMEV-IDD in these animals, therefore, may involve active inhibition of a "latent" disease susceptibility. PMID- 8347467 TI - Characterization of an inhibitory factor derived from epithelial cells of the small intestine. AB - Rat small intestine epithelial cell (EC) culture conditioned media (ECCM) contains a factor that has inhibitory activity against: a) the response of freshly isolated lymphocytes to Concanavalin A (Con A) or IL-2, b) the proliferative response to antigen of primed lymphocytes, and c) the normal growth of transformed cell lines derived from several species. Inhibition is reversible, and not the result of a cytotoxic effect. The inhibitory activity is enterocyte derived, effective at low concentration (1-2% in growth media), and can be derived from freshly isolated EC. Biochemical analysis indicates the inhibitory activity is associated with a protein with an approximate molecular weight of 32 kd, and an isoelectric point (PI) in the range of 3-5. The protein is trypsin sensitive, and labile with prolonged heating at 56 degrees C. The described activity differs from previously reported mucosally-derived inhibitory activities on the basis of molecular weight, and its ability to inhibit the growth of several cell lines. We suggest that this factor can provide the immunomodulatory activity necessary to produce the low level of intestinal T cell reactivity that is observed in vivo. PMID- 8347466 TI - Measurement of tumor necrosis factor alpha mRNA in small numbers of cells by quantitative polymerase chain reaction. AB - We have developed a method to quantitate TNF alpha-mRNA in small numbers of cells by reverse transcription followed by competitive polymerase chain reaction (RT PCR). RT-PCR allowed the accurate quantitation of TNF alpha-mRNA over a 1000-fold range of concentration. The recovery of RNA isolated from 1000 to 10,000 cells was optimized by reducing sample volumes and by adding 1 microgram yeast RNA. Using these modifications we accurately measured TNF alpha-mRNA in as little as 10,000 U937 cells by RT-PCR. Then we measured TNF alpha-mRNA in lamina propria mononuclear cells isolated from uninflamed and inflamed colonic mucosa from patients with inflammatory bowel disease (IBD). A 9-fold increase (5.4 copies per cell) was found in mononuclear cells from the gut of the inflamed regions compared to those cells from the uninflamed regions (0.6 copies per cell). These findings demonstrated the utility of this method in measuring differences of expression of the TNF-alpha gene in small number of cells isolated from tissues. PMID- 8347468 TI - Distribution and quantitation of plasma cells, T lymphocyte subsets, and B lymphocytes in bronchus-associated lymphoid tissue of chickens: age-related differences. AB - Development of the lymphoid cell compartment in bronchus-associated lymphoid tissue (BALT) of specific pathogen free chickens was examined. Specifically, B lymphocytes, T cell subsets (CD4 and CD8), and IgA-, IgG-, and IgM-producing plasma cells were labeled using immunocytochemical methods. Immunoglobulin producing cells (IgPC) were quantitated, and comparisons of IgPC numbers were made among chickens of different ages, among immunoglobulin isotypes, and between lymphoid (BALT) and nonlymphoid (non-BALT) areas in the primary bronchus. At hatching, BALT was devoid of IgPC, but by 2 weeks of age cells producing IgA, IgG, and IgM were present. Initially, there were approximately equal numbers of IgA-, IgG-, and IgM-PC; after 2 weeks of age, however, IgG- and IgM-PC outnumbered IgA-PC. At all ages, IgPC were more numerous in non-BALT regions of the primary bronchus than in BALT regions. Small numbers of T and B lymphocytes were present in BALT from 1-day old chickens, but substantial populations of these cells were not seen until 1-2 weeks of age. T helper (CD4+) cells were found near B cell regions in BALT lymphoid nodules, while T cytotoxic/suppressor (CD8+) cells were more evenly distributed throughout the nodules and in the epithelium. B lymphocytes predominated in germinal centers and also overlapped CD4+ populations adjacent to germinal centers. Lymphocyte cell types needed to initiate and regulate immune responses are present in chicken BALT and may be involved in protecting poultry from respiratory pathogens. PMID- 8347469 TI - Immunoglobulin transfer from immune-reconstituted SCID mice to nursing neonates: blood distribution of antibody and association with perinatal virus protection. AB - Previous work in our laboratory has shown that fetal protection from maternal transmission of the murine lactate dehydrogenase-elevating virus (LDV) infection is mediated by adoptive transfer of maternal anti-viral immunity. In the present report, we have characterized reconstitution of immunity in immunodeficient SCID mice following transplantation with BALB/c spleen cells, and studied the fate and distribution of maternally-derived antibodies after passage to neonatal SCID mice by nursing. Immune-reconstituted SCID mice maintained stable immunity for up to 7 months post-transplantation, during which time they produced nonneutralizing IgG anti-LDV antibodies and protected their offspring from maternally-derived LDV infection. Using IgG isotype and allotype assays, it was found that maternal IgG antibodies transferred from breast milk to nursing neonatal mice and appeared in their circulation. Weaning of SCID mice from immunocompetent mothers permitted the determination of blood immunoglobulin isotype half-lives (3.6-10.6 days) in the absence of endogenous antibody production. LDV infection was transferred to nursing mice by nonimmune LDV-infected mothers, but protection from nursing acquired LDV infection was associated with maternal viral immunity, breast milk transfer of IgG anti-LDV to nursing mice, and reduced breast milk virus titers. These findings show a nursing pathway for LDV infection, and demonstrate the potential of immune protection from this infection pathway. PMID- 8347470 TI - Inhibition of antigen-induced secretion in the rat jejunum by interferon alpha/beta. AB - Intestine from rats sensitized to egg albumin (EA) antigen responds to EA challenge with an increase in short-circuit current (Isc), indicative of predominantly chloride secretion. Here, we have examined the role of interferon alpha/beta (IFN alpha/beta) in the control of this event. Muscle-stripped jejunal segments from sensitized rats, mounted in Ussing chambers, displayed a reduced response to EA-challenge in the presence of IFN alpha/beta (100-1000 U/ml), when the cytokine was incubated with the tissue for > or = 60 min; serosal and luminal responses were significantly reduced by ca.32-47% and ca.50-80%, respectively. Preabsorption with an anti-IFN alpha/beta antibody abolished this inhibition. IFN alpha/beta did not influence the secretory response of the tissues to histamine, serotonin, bethanechol, or forskolin, suggesting that IFN alpha/beta does not affect the epithelium directly. IFN alpha/beta had no effect on Isc changes induced by electrical transmural stimulation of mucosal nerves in the tissue, nor did neuronal blockade with tetrodotoxin influence the action of IFN alpha/beta. These data indicate that the effect of IFN alpha/beta is not neuronally mediated. The normal anti-secretory actions of diphenhydramine (H1-antagonist) and piroxicam (cylooxygenase inhibitor) upon antigen-activation of mast cells, were not apparent in the presence of IFN alpha/beta. This suggests that IFN alpha/beta inhibits intestinal hypersensitivity by acting directly on mast cells. This hypothesis was confirmed by inhibition of antigen-induced release of the specific mucosal mast cell marker, rat mast cell protease II, in tissues treated with IFN alpha/beta. These findings suggest that IFN alpha/beta can function as an intestinal anti-inflammatory agent by stabilizing mucosal mast cells. PMID- 8347471 TI - Regional dichotomy of interleukin-4 and -5 regulation of senescent B cell responses specific for cholera toxin in Peyer's patches, lamina propria, and mesenteric lymph nodes. AB - The capacity of exogenous interleukin-4 (IL-4) and IL-5 to augment the antigen specific senescent Peyer's patch (PP), lamina propria (LP), and mesenteric lymph nodes (MLN) B cells was investigated in the present studies. CTx-primed lymphocytes in the PP, LP, and MLN were obtained from 4-and 24-month old C57BL/6J male mice, 14 days after oral immunization with cholera toxin (CTx). Cells were cultured optimally for 4 days either alone, with lipopolysaccharide (LPS), with LPS plus recombinant IL-4 or IL-5, or with LPS plus IL-4 or IL-5 plus monoclonal antibodies specific for the respective interleukin. Culture supernantants were tested for IgA and IgG anti-CTx antibodies by an ELISA assay. The data indicated impaired antibody responses of aged PP and MLN B cells by the lack of LPS plus IL 4 induced enhancement of anti-CTx IgG antibody production as compared with the young group. For anti-CTx IgA production, aged LP and MLN B cells did not respond equally as well to LPS plus IL-5 stimulation as the young group. In contrast, aged PP B cells responded equally as well by anti-CTx IgA production to LPS plus IL-5 stimulation as the young group. Both anti-IL-4 and anti-IL-5 Mabs blocked the respective IL-4 and IL-5-induced enhancement of antigen-specific IgG or IgA antibody production. The findings suggest a regional dichotomy of IL-5 induced enhancement of aged IgA-producing B cells specific for CTx in the Peyer's patches, mesenteric lymph nodes, and lamina propria. PMID- 8347472 TI - Acquired immunodeficiency syndrome (AIDS)--data as at 30 June 1993. PMID- 8347473 TI - The current global situation of the HIV/AIDS pandemic. PMID- 8347474 TI - Molecular epidemiology studies of cancer in families. PMID- 8347475 TI - Fatigue in cancer patients. AB - In this paper an overview is presented on what is currently known of fatigue in cancer. Fatigue is considered to be a multi-dimensional concept, that should be measured as such. However, fatigue has been assessed mostly by single items in general symptom checklists. The few specific instruments that have been used in cancer patient populations are discussed. The majority of cancer patients, about 70%, report feelings of fatigue during radio- or chemotherapy. Follow-up results show that, at least for some diagnoses, patients remain fatigued long after treatment has ended. Somatic and psychological mechanisms that have been proposed to explain fatigue are discussed. It is argued that the significance of the results obtained on fatigue as a symptom in cancer depends on comparison with other patient and non-patient populations. Also the occurrence of a response shift has to be considered, leading to under reporting of fatigue. Finally, possible interventions to decrease feelings of fatigue are presented. PMID- 8347476 TI - Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster. AB - In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel 3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers. PMID- 8347477 TI - Glutathione S-transferase expression in benign and malignant ovarian tumours. AB - Glutathione S-transferase sub-types alpha, mu and pi were assessed by immunocytochemistry in 109 biopsies of ovarian tissue, comprising malignant epithelial tissue in 86 cases and tissue of ovarian origin considered to be normal in 23. Glutathione S-transferase pi was the most prevalent, being present in all except one malignant epithelium studied and 83% of non-malignant tissue. There were no significant differences in the overall distribution of positive staining for alpha, mu and pi in the malignant and non-malignant biopsies, although the intensity of staining was greater in the malignant epithelium. Stromal staining was in general more pronounced in the malignant biopsies, and this was particularly prominent in the case of the alpha sub-type. Positive staining was seen more frequently in the less well-differentiated tumours, and a diffuse cytoplasmic pattern was the most common observation in tumours of moderate and poor differentiation. There was no significant association between survival and the presence or absence of sub-type staining of alpha and mu sub type. For the sub-type pi, patient survival was found to correlate with the intensity of staining (on a 0-(+++) scale). Those patients showing resistance to cytotoxic chemotherapy were found to have a higher intensity of staining for GST pi than responding patients. PMID- 8347478 TI - In vitro platinum drug chemosensitivity of human cervical squamous cell carcinoma cell lines with intrinsic and acquired resistance to cisplatin. AB - The platinum drug chemosensitivity of five human cervical squamous cell carcinoma cell lines (HX/151, HX/155, HX/156, HX/160 and HX/171) derived from previously untreated patients has been determined. Compared to our data obtained previously using human ovarian carcinoma cell lines, all five lines were relatively resistant to cisplatin, carboplatin, iproplatin and tetraplatin. One of the lines (HX/156) was exceptionally sensitive to the novel platinum (IV) ammine/amine dicarboxylates JM216 [bis-acetatoammine dichloro (cyclohexylamine) platinum (IV)] and JM221 [ammine dibutyrato dichloro (cyclohexylamine) platinum (IV)]. The range in IC50 values across the five lines was approximately 2.5-fold for cisplatin, carboplatin and iproplatin, 13-fold for tetraplatin and JM216, and 25-fold for JM221. No significant correlation (P > 0.05) was observed between platinum drug chemosensitivity and either glutathione levels or cadmium chloride sensitivity, an indicator of metallothionein levels. In addition, there was no significant correlation (P > 0.05) between cisplatin cytotoxicity and intracellular cisplatin accumulation or JM216 cytotoxicity and intracellular JM216 accumulation over the dose range 5-100 microM (2 h exposure). The exceptional sensitivity of HX/156 to JM216 appears, at least partially, to be a result of enhanced accumulation of JM216. An 8.6-fold acquired cisplatin resistant stable variant of HX/155 has been generated in vitro. Intracellular cisplatin accumulation was reduced by 2.4 +/- 0.3-fold (mean +/- s.d.) in HX/155cisR across the dose range 1-100 microM (2 h exposure). Glutathione levels in HX/155cisR were elevated by 1.3-fold in terms of protein content and by 1.6-fold in terms of cell number. HX/155cisR was 1.9-fold resistant to cadmium chloride. Total platinum bound to DNA after cisplatin exposure (10, 25, 50 or 100 microM for 2 h) was 3.6 +/- 0.6-fold (mean +/- s.d.) lower in HX/155cisR. Hence the mechanism of acquired cisplatin resistance in HX/155cisR appears to be multifocal, with reduced intracellular drug accumulation and elevated glutathione and metallothionein levels combining to reduce DNA platination levels. While HX/155cisR was cross-resistant to tetraplatin and carboplatin, novel platinum (II) and (IV) ammine/amine complexes, including JM216 and JM221, partially circumvented resistance (resistance factors of 1.5-2). Non cross-resistance was observed to iproplatin and nine non-platinum anticancer agents. Intracellular tetraplatin accumulation was reduced by 1.8 +/- 0.1-fold (mean +/- s.d.) in HX/155cisR across the dose range 1-100 microM (2 h exposure). In contrast, after JM216 exposure (1-100 microM for 2 h), no significant difference in intracellular platinum levels between HX/155 and HX/155cisR was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8347479 TI - Sequence dependence of the hyperthermic potentiation of carboplatin-induced cytotoxicity and intracellular platinum accumulation in HeLa cells. AB - We have examined the enhancement of cytotoxic effects of cis-diammine-1,1 cyclobutane dicarboxylate platinum(II) (carboplatin) by hyperthermia in HeLa cells using different regimes of timing and sequence. The results were compared with those obtained with cis-diamminedichloroplatinum(II) (cisplatin). We found that cisplatin simultaneously combined with heat was the most cytotoxic toward HeLa cells of the various timing and sequencing conditions studied. On the other hand, for carboplatin, drug treatment immediately following or during heat exposure showed the greatest effect. Intracellular platinum concentration in HeLa cells treated with heat before carboplatin showed a 2.75-fold increase over that in cells treated with the drug alone. The ratios for carboplatin given before, or during heating, were 0.67 and 1.42 respectively. Simultaneous exposure of cells to cisplatin and heat led to a 1.64-fold enhancement in cisplatin accumulation, compared to 0.92- and 1.24-fold increase for cells treated with cisplatin before and after heat respectively. Although each drug exposure prior to heat was less cytotoxic toward HeLa cells than any other heat/drug combination sequences, the platinum concentration was less than seen with each drug alone. Even though heat exposure prior to and during carboplatin showed a similar toxicity, platinum concentration in cells treated with heat prior to carboplatin was higher than that in cells treated with heat and carboplatin simultaneously. Thus, increased cytotoxicity cannot always be explained on the basis of intracellular platinum concentration. It is clear however that, differing from cisplatin, exposure of cells to heat prior to or during carboplatin administration results in the greatest cell kill. PMID- 8347480 TI - Structural and functional contributions to the G1 blocking action of the retinoblastoma protein. (the 1992 Gordon Hamilton Fairley Memorial Lecture). AB - The retinoblastoma gene product (RB) contributes to normal cell growth control. One of its functions is manifest as a block to exit from G1, which is carried out by an RB subspecies which is un- or underphosphorylated. After RB phosphorylation, a process which occurs towards the end of G1 in cycling cells, the block is lifted allowing a cell to enter S. Here, we review a series of results which speak to the elements of RB structure which contribute to this activity. Included is its internal colinear protein receptor domain (i.e. the 'pocket'). PMID- 8347482 TI - Pharmacology and antitumour effects of intraportal pirarubicin on experimental liver metastases. AB - Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P < 0.02 b vs c). Intraportal pirarubicin seems to be well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination. PMID- 8347481 TI - Further evaluation of nicotinamide and carbogen as a strategy to reoxygenate hypoxic cells in vivo: importance of nicotinamide dose and pre-irradiation breathing time. AB - The combination of nicotinamide and carbogen breathing is awaiting clinical evaluation as a strategy to overcome tumour hypoxia and thus enhance radiation response. We have continued our evaluation of this approach in the murine SCCVII tumour with the aim of determining the importance of nicotinamide dose and the pre-irradiation breathing time (PIBT) for carbogen. For carbogen breathing alone maximal enhancement of radiation response was observed with PIBT's of between 5 and 30 min. When nicotinamide (1,000 mg kg-1 IP) was administered 60 min prior to irradiation little or no variation in radiation response was observed for all the PIBT's examined (5-90 min). Indeed at all PIBT's the cell survival obtained for the carbogen nicotinamide and radiation combination was indistinguishable from that expected for a fully aerobic response. For PIBT's of 15 and 60 min we examined the influence of nicotinamide doses between 50 and 1,000 mg kg-1. Significant radiosensitizing effects were observed for all nicotinamide doses tested above 50 mg kg-1. Moreover for doses of 250 mg kg-1 and above the cell survival data was consistent with that expected for a fully aerobic response. No additional benefit accrued from raising the nicotinamide dose above 250 mg kg-1. These results indicate that significant radiosensitization may be expected even with clinically achievable nicotinamide doses when it is combined with carbogen breathing. Furthermore, the use of nicotinamide may reduce the critical importance of PIBT on the radiosensitization observed with carbogen. PMID- 8347483 TI - Insulin-like growth factor I activates the invasion suppressor function of E cadherin in MCF-7 human mammary carcinoma cells in vitro. AB - The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells. PMID- 8347484 TI - Detection of an oestrogen receptor-like protein in human meningiomas by band shift assay using a synthetic oestrogen responsive element (ERE). AB - When a ligand binding or enzyme immunoassay is used, meningiomas are found to be rich in progestin receptors (PR) whereas oestrogen receptors (ER) are virtually undetectable. A protein that can bind to an oestrogen responsive element (ERE) was detected in meningiomas, by using the band-shift assay. The binding of ER to the ERE is inhibited by the anti-ER monoclonal antibody ER-P31, which is directed to the A/B domain of the ER, indicating that the binding protein is an ER-like protein. PMID- 8347486 TI - Mechanism of muscle protein degradation in cancer cachexia. AB - Depletion of skeletal muscle mass in animals bearing an experimental model of cachexia, the MAC16 adenocarcinoma, occurs by a reduction in protein synthesis accompanied by a large increase in protein degradation. Serum from mice bearing the MAC16 tumour produced an increased protein degradation in isolated gastrocnemius muscle, as measured by tyrosine release, with a maximal effect occurring with serum from animals with a weight loss of between 11 and 20%. The response was specific to the cachectic state, since serum from mice bearing the MAC13 adenocarcinoma, which does not produce weight loss, did not increase tyrosine release from gastrocnemius muscle above that observed with serum from non tumour-bearing animals. The circulatory proteolysis-inducing factor was stable to heating at 60 degrees C for 5 min and was not inhibited by phenylmethylsulfonyl fluoride, suggesting that it was not a serine protease. The level of prostaglandin E2 (PGE2) in gastrocnemius muscle was significantly elevated after incubation with serum from cachectic mice bearing the MAC16 tumour. Both indomethacin and the polyunsaturated fatty acid eicosapentaenoic acid (EPA) inhibited the rise in muscle PGE2 content in response to serum from cachectic mice and also inhibited muscle protein degradation. These results suggest that muscle protein degradation in cancer cachexia is associated with a rise in PGE2 content. PMID- 8347485 TI - Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour. AB - Engineering of a variety of rodent tumour cells to secrete either interleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to reduce their tumorigenicity. However the mechanisms of action of secreted IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 had reduced growth rate and in some cases was rejected by syngeneic animals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immunohistochemical analysis of tumour nodules undergoing regression showed stimulation of a largely lymphocytic infiltrate by IL-2 and a macrophage and granulocyte infiltrate, with a small number of lymphocytes by IL 4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines might mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixed, unmodified FS29 cells. The loss of cytokine secreting cells from such admixtures occurred more rapidly for IL-2-secreting cells. Injection of IL-4-secreting, but not IL-2-secreting FS29 cells could protect mice from a delayed challenge with unmodified FS29 cells. These data suggest that IL-4 secretion stimulates the better long-term host anti-tumour response. PMID- 8347488 TI - Detecting fatty acids of dietary origin in normal and cancerous human breast tissue by 13C nuclear magnetic resonance spectroscopy. AB - Natural abundance 13C NMR was used to determine relative amounts of fatty acid subclasses present in fibroadipose tissue from the human breast in healthy and cancer patients and in breast carcinoma tissue. Resonances corresponding to the carbon atoms of triacylglycerides were obtained when adipose tissue constituted more than 10% of the carcinoma. Resonances corresponding to phospholipids and proteins were also observed when the percentage of adipose tissue was lower. No significant difference between the levels of unsaturated fatty acids in adipose tissue from cancer and non-cancer patients was found. However, significant differences in the levels of monounsaturated and saturated fatty acids of carcinoma compared to non-cancerous tissue was found, as was a nearly significant difference for the levels of polyunsaturated fatty acids in these two tissue types. These findings suggest an alteration of cellular lipid composition in neoplastic mammary tissue. PMID- 8347487 TI - Low density lipoprotein for cytotoxic drug targeting: improved activity of elliptinium derivative against B16 melanoma in mice. AB - Significant low density lipoprotein (LDL) uptake by tumour cells led to the use of LDL as a discriminatory vehicle for the delivery of cytotoxic drugs. In the current study, the lipophilic elliptinium derivative, elliptinium-oleate (OL NME), was incorporated into LDL to reach an incorporation level of 400 molecules per LDL particle. The OL-NME-LDL complex showed cytotoxic effects on normal human fibroblasts while the cytotoxicity was not observed on receptor-defective human fibroblasts, indicating the ability of the complex to be preferentially metabolised by the LDL receptor. In vivo metabolism of the complex was related to the LDL receptor pathway. The metabolic clearance was the same for native LDL (17.1 ml h-1) and OL-NME-LDL complex (16.2 ml h-1). LDL incorporated OL-NME enhanced the anti-tumour activity against murine B16 melanoma model; this resulted from increased efficacy for OL-NME-LDL at doses equal to free 9-OH-NME (157 vs 76 of Increase Life Span (ILS) (%) values after intraperitoneal (i.p.) drug injection on i.p. implanted tumour model and 45 vs -2 ILS (%) values after intravenous drug injection on subcutaneous implanted tumour model). These data suggest that LDL improves the potency of lipophilic cytotoxic drugs against tumours that express LDL receptor activity. PMID- 8347489 TI - Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles. AB - The interaction of membrane-active amphiphiles with a series of MDR Chinese hamster ovary (CHO) cell lines was investigated. Cross-resistance to cationic amphiphiles was observed, which was effectively sensitised by verapamil. MDR cells showed collateral sensitivity to polyoxyethylene amphiphiles (Triton X 100/Nonidet P-40), which reached a maximum at 9-10 ethylene oxide units. Resistant lines were also highly collaterally sensitive (17-fold) to dibutylphthalate. mdrl transfectants showed cross-resistance to cationic amphiphiles, but no collateral sensitivity to nonionic species. Triton X 100/Nonidet P-40 inhibited 3H-azidopine photoaffinity labelling at low concentrations, perhaps reflecting a specific interaction with P-glycoprotein. Further investigation of the molecular basis of collateral sensitivity revealed that association of 3H-Triton X-100 with MDR cells reached steady state levels rapidly, and occurred by a non-mediated mechanism. The equilibrium level of X-100 uptake was inversely related to drug resistance. Collateral sensitivity is thus not a result of decreased Triton X-100 association with the cell. The fluorescent probe merocyanine 540 was used to examine the MDR plasma membrane microenvironment for physicochemical changes. Increasing levels of drug resistance correlated with a progressive shift in the mean cell fluorescence to lower levels, which suggests that the packing density in the outer leaflet of MDR cells is increased relative to that of the drug-sensitive parent. PMID- 8347490 TI - Interferon plus tamoxifen treatment for advanced breast cancer: in vivo biologic effects of two growth modulators. AB - The effects of interferon-alpha (IFN) plus tamoxifen (TMX) in the treatment of advanced breast cancer were assessed. Changes of in vivo biologic determinants including hormone receptors, P24 protein, Ki-67 and growth factor expression were evaluated. Seven patients with advanced, heavily pretreated, breast cancer with accessible disease, underwent biopsy prior to and after sequential treatment with IFN and IFN plus TMX. Clinically 4/7 patients responded to treatment with one complete and three partial remissions. Apart from the favourable response rate the sequential in vivo changes in expression of tumour variables were of considerable interest. IFN treatment consistently increased the expression of the estrogen receptor (ER) and of the estrogen regulated protein P24 while decreasing the expression of the proliferation associated antigen Ki-67. Addition of TMX on the other hand resulted in a reduction of ER expression to pre-IFN levels and a rise in progesterone receptor (PR) expression. When the effect of either IFN or IFN plus TMX on the expression of two growth factors was assessed they were found to be somewhat variable. While PDGF expression tended to be suppressed, there was no clinical correlation with response to therapy. TGF beta expression was found in all patients prior to treatment and while all non-responders showed reduction of TGF beta following treatment, the alterations were variable amongst responders (including two patients with increased expression, one with no change, and one with decreased expression). It is concluded that both IFN and TMX exert multiple effects on the expression of tumour biologic variables and that while the study confirmed some of the predictions from in vitro models, the in vivo effect are more complex than has been appreciated from the models. From the clinical point of view, it might be expected that treatment which enhances the expression of ER in tumours should have a positive effect on the response to TMX. PMID- 8347491 TI - Congenital abnormalities in children with cancer and their relatives: results from a case-control study (IRESCC). AB - Several studies have revealed an excess of malformations in children with certain malignancies. A few environmental causes have been identified which may damage the foetus and lead to malformation and cancer. However, most of the numerous recognised cancer/malformation syndromes are genetically determined. This report describes a case-control study of 555 newly diagnosed children with cancer and 1,110 matched controls, chosen from general practitioner lists (GP controls) and hospital admissions (H controls). Their parents were interviewed on topics of possible aetiological significance and medical records were checked to confirm reports at interview. The numbers of congenital malformations in the index and GP control children, and the relatives of the index children, the GP and H controls are described. There were more children with malformations among the cases (60/555) than among the GP controls (27/555), P < 0.001. The abnormalities in the cases included eight with specific chromosomal/genetic conditions (e.g. Down's syndrome, XY gonadal dysgenesis, Von Recklinghausen's neurofibromatosis, Goldenhar's syndrome) whereas only one GP control child had a chromosomal defect (P < 0.05). Five case children but no GP controls had neural tube defects; this is not statistically significant. No excess of malformations was found in the siblings of cases compared with GP and H control siblings. Case mothers had a small excess of malformations (22/555) compared with GP controls (8/555), P < 0.05. Among more distant relatives the results were difficult to interpret because of the relatively small numbers in the diagnostic subgroups and because of apparent under reporting in grandparents, but no striking differences were seen between case and control relatives. The excess of malformations found in children with cancer, compared with controls, without a similar excess of malformations in their close relatives may indicate that in some (perhaps very roughly one in 20) cases antenatal events may lead both to the malformation and the malignancy. PMID- 8347492 TI - Interleukin-2 receptor and ovarian cancer. AB - Interleukin-2 receptor (IL-2R) can be detected in serum. We estimated the IL-2R in the serum of 78 women, of whom 30 were diagnosed as having malignant ovarian tumours, five had non ovarian tumours, one had a negative second look laparotomy, 11 had benign ovarian tumours, three had uterine fibroids and 28 were age-matched controls. The results indicated that the serum IL-2R of these patients was significantly elevated in ovarian cancer patients compared to both controls (P < 0.0001) and benign ovarian tumours (P < 0.0002). There were no significant differences in IL-2R levels between stage of disease and degree of differentiation within the ovarian tumour group. PMID- 8347493 TI - Smear misclassification in a cervical cancer screening programme. AB - A nested case-control study was undertaken in the Maribo County cohort of 27,811 women with negative Pap smears. Sixty women who later developed invasive cervical cancer constituted the cases, and five matched controls were selected from the cohort for each case. A total of 633 previous, negative smears for the cases and controls were reviewed independently by two pathologists. The review showed misclassification to be frequent in these smears collected in the period 1966-82. Thirty-five smears were considered positive at the review. The misclassification was differential in respect to the women's later disease status. The odds ratio for patients compared with controls for having at least one positive smear was 22.12 (95% CI 7.54-64.94). We were unable to identify specific characteristics of misclassified smears coming from later cases. Koilocytosis/dyskeratosis, herpes virus changed cells and hyperkeratosis were equally rare in smears from patients and controls. The Maribo County data indicate that the fraction of preventable cases of invasive cervical cancer in women aged 30-64 within the first 5 years after a negative smear could be increased from 62-72% to 83-86%, if misclassification of true positive smears could be eliminated. As a rough estimate, this would be at the cost of a 2% increase in the work load. It should be remembered that there is a large element of extrapolation in applying these results based on relatively poor quality specimens from 1966-82 as compared to a modern screening service. PMID- 8347494 TI - PS2 in breast cancer--alternative or complementary tool to steroid receptor status? Evaluation of 446 cases. AB - The oestrogen induced pS2 protein was measured in the cytosol of 446 breast cancer samples by an immunoradiometric assay. The relationships between pS2 and several clinical and biological parameters were evaluated. pS2 was not correlated to age, pT and nodal status, while it was higher in pre- than in peri- and post menopausal women. A statistically significant positive association was found between pS2 and ER, PgR and cathepsin D. However, the frequency of pS2 negative values in ER+ (25.6%), PgR+ (21.7%) and cathepsin D-(19.0%) cases suggests that pS2 provides information independent of the above parameters in a fairly high percentage of patients. The prognostic role of pS2 was evaluated in 267 cases (follow up time 24-102 months). pS2+ showed longer RFS (P = 0.016) and OS (P = 0.004) than pS2-. pS2+ cases were significantly associated with a better prognosis in N+ but not in N- cases. Multivariate analysis showed that pS2 is an independent prognostic factor being the second most effective indicator for OS after nodal status and the third for RFS after nodal status and cathepsin D. From the present findings, we conclude that pS2 probably provides additional biological information to steroid receptor status and cathepsin D in patients with primary breast cancer. PMID- 8347495 TI - Failure to detect early breast cancer using in vitro nuclear magnetic resonance spectroscopy of plasma. AB - Water suppressed proton nuclear magnetic resonance (1H NMR) spectroscopy of human plasma has been described as successful in detection of malignancy. We designed a prospective study to test the hypothesis that in vitro NMR spectroscopy has a high sensitivity for detecting early breast cancer. One hundred and thirty-five women were referred for breast biopsy due to abnormal mammograms. One hundred of these were recruited through a population-based mammography screening project. Sixty-nine of 135 women were found to have breast cancer and their average line width of the methyl and methylene resonance in the plasma were compared to those women who had a benign or normal histopathology in the biopsy and to the line width for 100 healthy subjects from the same population. The mean line width at a half-height of the methyl and methylene resonances of the serum lipoprotein lipids in the NMR spectrum did not differ appreciably between the groups. The line width correlated highly with the serum triglycerides, but correction for the level of triglycerides did not improve the diagnostic accuracy of the line width. Receiver-operating characteristic analysis revealed a sensitivity of 61% and a false positive rate of 43% at the most beneficial cut-off of line width (39.7 Hz). In vitro NMR spectroscopy in our hands was thus not a useful diagnostic tool in patients with early breast cancer. PMID- 8347496 TI - p53 immunoreaction in endoscopic biopsy specimens of colorectal cancer, and its prognostic significance. AB - The expression of p53 protein was immunohistochemically studied in formalin-fixed paraffin-embedded biopsy specimens of 203 colorectal carcinomas by use of a monoclonal antibody specific for the p53 protein. PAb1801. p53 protein expression with its reactivity localised in nuclei was found in 121 (59.6%) of the cancers. There was no correlation of p53 immunoreactivity with histological classification, wall invasion, lymphatic invasion, venous invasion, lymph node metastases, or peritoneal metastases. p53-positive cancers were more frequently associated with liver metastasis than p53-negative ones. Patients with p53 positive tumours had significantly poorer prognoses than those with p53-negative tumours. The 5 year survival rate was 58.1% for patients with p53-positive tumours, and 76.3% for those with p53-negative tumours. In Dukes' stage C tumours, an especially good correlation was found between p53 immunoreactivity and prognosis. In addition, patients with p53-positive tumours had higher recurrence rates. The results indicate that p53 immunoreactivity may be a useful prognostic marker of colorectal cancers. PMID- 8347497 TI - Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody. AB - Fifty-two patients with epithelial ovarian cancer were treated with yttrium-90 labelled monoclonal antibody HMFG1 administered intraperitoneally following conventional surgery and chemotherapy as part of an extended phase I-II trial. The treatment was well tolerated and the only significant toxicity observed was reversible myelosuppression as previously described. Following conventional surgery and chemotherapy, 21 out of the 52 patients had no evidence of residual disease and were regarded as receiving treatment in an adjuvant setting. To date, two of these patients have died of their disease (follow-up 3-62 months, median follow-up 35 months). This extended phase I-II study suggests that patients with advanced ovarian cancer who achieve a complete remission following conventional therapy may benefit from further treatment with intraperitoneal radioactive monoclonal antibody. PMID- 8347498 TI - Over-expression of the c-myc proto-oncogene in colorectal carcinoma. AB - Alterations in the c-myc proto-oncogene in colorectal cancer were studied at the level of RNA expression, gene amplification and rearrangements. One hundred cases of colorectal cancer, stratified by Dukes' stage were examined. The level of messenger RNA expression was measured in tumours and matched normal mucosa from the same patient. Between 5 and 400 fold over-expression was found in 66% of tumours. Neither the presence nor the level of over-expression correlated with tumour staging. A significant correlation (P < 0.01) was found between over expression of c-myc in tumours and the presence of synchronous adenomas elsewhere in the colon. In contrast to other tumours, no rearrangements of the gene were found on Southern analysis of colorectal cancers. Similarly, amplification of the gene was not found in the cancers examined. PMID- 8347499 TI - Measurement of growth rate of lung metastases in 21 patients with bone or soft tissue sarcoma. AB - The volume doubling time (T2) of 52 lung metastases in 21 patients was calculated from measurements done on plain chest radiographs. Follow-up times ranged from 14 to 819 days. The measurements were fairly well reproducible in the majority of patients, although considerable discrepancies in T2 estimates made by two independent observers were found in a few patients. The median doubling time was 34.9 days (estimated 95% range 3.9 to 352 days). The variation of T2:s between patients was significantly (P = 0.0001) larger than that between T2: of multiple metastases in the same patients. The growth of the metastases seemed to be well described by a simple exponential function in all patients with more than two measurements, without evidence of Gompertzian growth. There seemed to be a linear correlation between the logarithm of T2 and log-survival time from diagnosis of metastatic disease, even if only one third of the variation of survival times between patients could be explained by differences in T2. T2 was not a significant factor for survival in Cox-analysis (P = 0.10). PMID- 8347501 TI - Tumours of the central nervous system and serum sialic acid concentration in men and women. AB - In a population-based study serum sialic acid level was examined in relation to subsequent development of central nervous system (CNS) tumours (229 cases). Significantly increased sialic acid concentration was found in men with a malignant CNS tumour diagnosed within 8 years of analysis, compared with corresponding matched controls. These findings suggest that the tumour existed at the time of examination which is supported by a negative linear association between sialic acid level and the time from screening to tumour diagnosis. PMID- 8347500 TI - A phase I study of intravenous bryostatin 1 in patients with advanced cancer. AB - Bryostatin 1 is a novel antitumour agent derived from Bugula neritina of the marine phylum Ectoprocta. Nineteen patients with advanced solid tumours were entered into a phase I study to evaluate the toxicity and biological effects of bryostatin 1. Bryostatin 1 was given as a one hour intravenous infusion at the beginning of each 2 week treatment cycle. A maximum of three treatment cycles were given. Doses were escalated in steps from 5 to 65 micrograms m-2 in successive patient groups. The maximum tolerated dose was 50 micrograms m-2. Myalgia was the dose limiting toxicity and was of WHO grade 3 in all three patients treated at 65 micrograms m-2. Flu-like symptoms were common but were of maximum WHO grade 2. Hypotension, of maximum WHO grade 1, occurred in six patients treated at doses up to and including 20 micrograms m-2 and may not have been attributable to treatment with bryostatin 1. Cellulitis and thrombophlebitis occurred at the bryostatin 1 infusion site of patients treated at all dose levels up to 50 micrograms m-2, attributable to the 60% ethanol diluent in the bryostatin 1 infusion. Subsequent patients treated at 50 and 65 micrograms m-2 received treatment with an intravenous normal saline flush and they did not develop these complications. Significant decreases of the platelet count and total leucocyte, neutrophil and lymphocyte counts were seen in the first 24 h after treatment at the dose of 65 micrograms m-2. Immediate decreases in haemoglobin of up to 1.9g dl-1 were also noted in patients treated with 65 micrograms m-2, in the absence of clinical evidence of bleeding or haemodynamic compromise. No effect was observed on the incidence of haemopoietic progenitor cells in the marrow. Some patients' neutrophils demonstrated enhanced superoxide radical formation in response to in vitro stimulation with opsonised zymosan (a bacterial polysaccharide) but in the absence of this additional stimulus, no bryostatin 1 effect was observed. Lymphocyte natural killing activity was decreased 2 h after treatment with bryostatin 1, but the effect was not consistently seen 24 h or 7 days later. With the dose schedule examined no antitumour effects were observed. We recommend that bryostatin 1 is used at a dose of 35 to 50 micrograms m-2 two weekly in phase II studies in patients with malignancies including lymphoma, leukaemia, melanoma or hypernephroma, for which pre-clinical investigations suggest antitumour activity. PMID- 8347503 TI - Phylogenetic analysis of some Aerococcus-like organisms from clinical sources: description of Helcococcus kunzii gen. nov., sp. nov. AB - 16S rRNA gene sequencing studies were performed on some unusual gram-positive catalase-negative cocci of unknown taxonomic position isolated from human clinical sources. Comparative analysis of the sequence data demonstrated that the clinical isolates represent a hitherto-unknown line of descent within the low-G+C content gram-positive bacteria. On the basis of the phylogenetic findings and the phenotypic distinctiveness of the organisms, it is proposed that they be classified in a new genus, Helcococcus, as Helcococcus kunzii sp. nov. The type strain of H. kunzii is NCFB 2900. PMID- 8347502 TI - Lymphocyte homing receptor (CD44) expression is associated with poor prognosis in gastrointestinal lymphoma. AB - Lymphocyte homing receptor (CD44) is involved in lymphocyte adhesion to endothelial cells of high endothelial venules (HEVs) and lymphocyte exit from the blood circulation, and it may be involved also in hematogenous dissemination of malignant lymphoma. Prognostic significance of lymphocyte homing receptor expression defined by Hermes-3 antibody was studied among 27 gastrointestinal lymphomas followed up for 8 to 20 years after the diagnosis. Lymphomas lacking or with very weak homing receptor expression (n = 14, 52%) were associated with 57% 10-year survival rate as compared with only 15% among lymphomas that expressed CD44 more strongly (P = 0.02). We conclude that lack of lymphocyte homing receptor expression is common in gastrointestinal lymphoma, and that CD44 expression is associated with unfavourable prognosis. PMID- 8347504 TI - Polyphasic taxonomy leading to the proposal of Moraxella canis sp. nov. for Moraxella catarrhalis-like strains. AB - The taxonomic position of a group of 16 Moraxella catarrhalis-like strains, isolated mainly from dogs, was examined by using morphological tests, biochemical tests, serology, ribotyping with oligonucleotide probes, polymerase chain reaction typing of the 16S rRNA gene and the 16S-23S rRNA gene spacer region, polyacrylamide gel electrophoresis of total proteins, fatty acid profiles, moles percent G+C, dot spot and in-solution DNA-DNA hybridizations, and DNA-rRNA hybridizations. It was found that these organisms constitute a distinct cluster within the genus Moraxella. Since they differ genotypically as well as phenotypically from previously described Moraxella species, a new species, Moraxella canis, is proposed to accommodate these isolates. The type strain is LMG 11194 (= N7 = CCUG 8415A). PMID- 8347505 TI - Phylogenetic diversity of phytopathogenic mycoplasmalike organisms. AB - By using specific primers, the 16S rRNA genes of Japanese mycoplasmalike organisms (MLOs) were amplified by polymerase chain reactions from MLO-enriched fractions of plants infected with each of six different MLOs. Each of the polymerase chain reaction fragments (length, 1,370 nucleotides) was directly sequenced in both strands by using 17 oligonucleotide primers. A phylogenetic tree constructed by using the sequence data showed that these Japanese MLOs are phylogenetically diverse microorganisms that fall into three groups, group I (onion yellows, tomato yellows, mulberry dwarf, and paulownia witches' broom MLOs), group II (tsuwabuki witches' broom MLO), and group III (rice yellow dwarf MLO). A high level of sequence homology (99%) between the Oenothera hookeri MLO and the severe strain of the western aster yellows MLO on the one hand and group I MLOs on the other indicates that the O. hookeri MLO and the severe strain of the western aster yellows MLO belong to group I and suggests that these MLOs, isolated from two geographically separated locations, descended from a very similar ancestor. Although group I contains phylogenetically identical MLOs, the organisms are transmitted by diverse insect vectors. The three MLO groups are more closely related to Acholeplasma laidlawii than to Mycoplasma gallisepticum. Thus, although MLOs are phylogenetically diverse, they are evolutionarily distant from other mollicutes. These data, together with other information (including phylogenetic relationships, vector specificity, plant-pathogenic properties, and habitat in plant phloem sieve tubes), suggest that MLOs could be classified into at least three phylogenetic groups (groups I through III). PMID- 8347506 TI - Molecular taxonomic studies of Actinomyces-like bacteria isolated from purulent lesions in pigs and description of Actinomyces hyovaginalis sp. nov. AB - The 16S rRNA gene sequence of some Actinomyces-like bacteria isolated from purulent lesions in pigs was determined. A comparative analysis of the rRNA sequence data revealed that the bacteria are members of the genus Actinomyces, but are phylogenetically distinct from Actinomyces suis. On the basis of our findings and the results of previous phenotypic studies it is formally proposed that the bacteria from pigs should be designated a new species, Actinomyces hyovaginalis. PMID- 8347507 TI - Moraxella lincolnii sp. nov., isolated from the human respiratory tract, and reevaluation of the taxonomic position of Moraxella osloensis. AB - A polyphasic taxonomic study was performed to determine the relationships of 10 Moraxella-like strains isolated mainly from the human respiratory tract in Sweden. Two of the strains formed a separate subgroup on the basis of both their protein contents and their fatty acid contents. However, the overall protein and fatty acid profiles revealed that all 10 strains were highly related. Representative strains of the two subgroups exhibited high DNA binding values (98%) with each other and had an identical DNA base ratio (44 mol% G+C). DNA-rRNA hybridizations revealed that this taxon can be included in the genus Moraxella, which is only distantly related to phenotypically similar genera, such as the genera Neisseria and Kingella. The results of an extensive phenotypic analysis indicated that the general biochemical profile of the 10 strains conforms with the description of the genus Moraxella given in Bergey's Manual of Systematic Bacteriology. We therefore consider these organisms members of a new Moraxella species, for which the name Moraxella lincolnii is proposed. Furthermore, we also conclude that Moraxella osloensis belongs, genotypically as well as phenotypically, to the genus Moraxella. PMID- 8347508 TI - Serovar determination and molecular taxonomic correlation in Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum: a cooperative study of the International Working Group on Mycobacterial Taxonomy. AB - A cooperative study was conducted by the International Working Group on Mycobacterial Taxonomy to correlate the agglutination serovar designations of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum strains with the species ascriptions of these organisms according to molecular criteria and cultural properties and to assess the reproducibility of serovar determinations for a set of 63 reference strains of these species. Among the molecular criteria, the level of agreement between results obtained with nucleic acid probes and T-catalase serology results was 94% for strains of M. avium and M. intracellulare. Nucleic acid probes were not available for M. scrofulaceum, but none of the 10 strains ascribed to this species on the basis of catalase serology data reacted with a nucleic acid probe for M. avium or M. intracellulare. Ascription to a species on the basis of mycolic acid high performance liquid chromatography patterns was in agreement with catalase serology results in 86% of the cases examined. Most strains belonging to serovars 1 through 6 and 8 through 11 were identified by molecular criteria as M. avium, most strains belonging to serovars 7, 12 through 20, 23, and 25 were identified as M. intracellulare, and most strains belonging to serovars 41 through 43 were identified as M. scrofulaceum, in agreement with common current practice. Evidence for assigning serovar 27 to M. scrofulaceum was obtained. However, two strains of a given serovar may, on occasion, be placed in different species. The dominant species assignments for strains belonging to serovars 21, 24, 26, and 28 remain unresolved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347509 TI - Phylogeny of species in the family Neisseriaceae isolated from human dental plaque and description of Kingella oralis sp. nov [corrected]. AB - Fourteen human periodontal isolates recovered from a purported Eikenella corrodens-selective medium containing 1 microgram of clindamycin per ml displayed biochemical traits which differed from those described for E. corrodens. These organisms were gram-negative rods which corroded agar. The isolates were oxidase positive and urease, indole, and esculin negative. They differed from E. corrodens in catalase, nitrate reduction, lysine decarboxylase, and ornithine decarboxylase activities. One isolate, strain UB-294, was presumptively identified as Kingella denitrificans. A second isolate, strain UB-204, differed from E. corrodens by being catalase positive and nitrate reduction negative. Twelve isolates, including strain UB-38T (T = type strain), were phenotypically similar to Kingella kingae except that they did not produce acid from maltose and were not beta-hemolytic. Essentially complete (1,480-base) 16S rRNA sequences were determined for strains UB-38T, UB-204, and UB-294 and the type strains of Neisseria animalis, Neisseria canis, Neisseria denitrificans, Neisseria elongata, Neisseria flavescens, Neisseria macaca, and Neisseria polysaccharea. These sequences were compared with the previously published sequences of six other species belonging to the family Neisseriaceae. On the basis of the results of the comparative sequence analysis, UB-294 was confirmed as a K. denitrificans strain, UB-204 was identified as a member of a new species which may belong in the genus Eikenella, and UB-38T was identified as a member of a new species of the genus Kingella, for which we propose the name Kingella oralis [corrected]. Since strain UB-204 was the only representative of a new species, it was not named.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347510 TI - Arhodomonas aquaeolei gen. nov., sp. nov., an aerobic, halophilic bacterium isolated from a subterranean brine. AB - Arhodomonas aquaeolei gen. nov., sp. nov., isolated from a petroleum reservoir production fluid, is described. The single isolate was an obligately halophilic, aerobic, gram-negative, oval rod-shaped bacterium that was actively motile by means of a single polar flagellum. It was catalase and oxidase positive. The isolate had a specific requirement for NaCl; growth occurred at NaCl concentrations between 6 and 20%, and optimal growth occurred in the presence of 15% NaCl. This species metabolized primarily organic acids and required biotin for growth. The name Arhodomonas is proposed for the new genus, which was placed in the gamma subclass of the Proteobacteria on the basis of the results of a 16S rRNA sequence analysis. Although A. aquaeolei is most closely related to purple sulfur bacteria (the genera Ectothiorhodospira and Chromatium), it is not a phototrophic microorganism, which is consistent with its isolation from a subterranean environment. The major components of its cellular fatty acids were C16:0, C18:1, C19:0, C16:1, and C18:0 acids. The DNA base composition of the type strain is 67 mol% G+C. The type and only strain is strain HA-1 (= ATCC 49307). PMID- 8347511 TI - A test for measuring growth responses of mollicutes to serum and polyoxyethylene sorbitan. AB - A test is described that is useful for characterizing mollicutes in terms of the ability to maintain growth in medium containing 15 to 20% fetal bovine serum or in serum-free media with or without 0.04% Tween 80 (polyoxyethylene sorbitan). Representative Acholeplasma species maintained growth in serum-free medium, and about half of the strains tested grew well in Tween 80-supplemented medium. Representative Mycoplasma and Entomoplasma species did not maintain growth in either serum-free medium alone or when Tween 80 was added. Spiroplasma species and group representatives generally failed to sustain growth in serum-free medium with or without Tween 80, but at least four of the spiroplasmas tested maintained growth in serum-free medium. The representative Mesoplasma species grew in serum free media only when Tween 80 was added, as did Mycoplasma lactucae. Although the test has obvious determinative uses for members of the class Mollicutes, it does not supplant the conventional methodology for assaying the cholesterol requirements of these organisms. PMID- 8347512 TI - Ileal symbiont intracellularis, an obligate intracellular bacterium of porcine intestines showing a relationship to Desulfovibrio species. AB - A new genus and species of obligate intracellular-bacteria found in porcine intestines are described. Growth on any bacteriological medium deprived of living cells has not been demonstrated. The organism has been grown intracellularly in cell culture. The 16S rRNA gene sequence data, DNA probe results, and microscopic observations provide evidence that these bacteria differ from those in other described genera and that they belong to the delta subdivision of the class Proteobacteria. We have amplified and sequenced the 16S ribosomal DNA of four preparations of the intracellular bacterium from pigs. For this, intracellular organisms were released and purified from the infected cells without culture techniques. After DNA purification, the polymerase chain reaction with primers complementary to highly conserved eubacterial sequences was used to amplify regions of 16S ribosomal DNA which were subsequently cloned (in some cases) and sequenced directly by standard techniques. The sequences obtained from each preparation were identical and were most similar to that of a sulfate-reducing proteobacterium, Desulfovibrio desulfuricans ATCC 27774 (91% similarity). An oligonucleotide probe complementary to a hypervariable region of the 16S rRNA sequence of the bacterium hybridized with intracellular organisms obtained from porcine intestines. The bacterium is a gram-negative, curved rod with tapered ends. It multiplies intracellularly in the cytoplasm of ileal epithelial cells by septation. The vernacular name Ileal symbiont (IS) intracellularis is proposed for this bacterium. The type strain of IS intracellularis is strain 1482/89 grown in cell culture from a pig affected by proliferative enteropathy. It is deposited in the National Collection of Type Cultures, Colindale, London, as NCTC 12656. PMID- 8347513 TI - Proposal of six new species in the genus Aureobacterium and transfer of Flavobacterium esteraromaticum Omelianski to the genus Aureobacterium as Aureobacterium esteraromaticum comb. nov. AB - Twelve strains placed in the genera Flavobacterium, Pseudomonas, and Aureobacterium, including soil isolates, were characterized taxonomically. On the basis of morphological, physiological, and chemotaxonomic data, as well as DNA DNA hybridization data, we propose that 11 of these strains should be classified in the genus Aureobacterium as new combinations or new species, as follows: Aureobacterium esteraromaticum comb. nov. (type strain, IFO 3751 [= ATCC 8091]), Aureobacterium arabinogalactanolyticum sp. nov. (type strain, IFO 14344), Aureobacterium keratanolyticum sp. nov. (type strain, IFO 13309), Aureobacterium luteolum sp. nov. (type strain, IFO 15074 [= DMS 20143]), Aureobacterium schleiferi sp. nov. (type strain, IFO 15075 [= DMS 20489]), Aureobacterium terrae sp. nov. (type strain, IFO 15300), and Aureobacterium trichothecenolyticum sp. nov. (type strain, IFO 15077 [= JCM 1358]). Whereas the peptidoglycan type of members of this genus is considered to be B2beta, the new species A. keratanolyticum was shown to have a new peptidoglycan type, murein variation B2alpha. An emended description of the genus Aureobacterium is presented. PMID- 8347514 TI - Phenotypic and genomic analyses of human strains belonging or related to Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium breve. AB - A numerical analysis based on phenotypic characteristics (89 enzymatic tests and 49 carbohydrate acidification tests), in which experimental strips from Biomerieux-API, La Balme les Grottes, France, were used, was performed to characterize 82 new isolates belonging or related to Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium breve. A total of 72 strains were isolated from child or adult feces, and the other strains were obtained from human vaginas and bronchi. In this study we also included 38 type and reference strains that were representative of all species of the genus Bifidobacterium and 6 strains belonging to the genus Lactobacillus. DNA-DNA relationships between B. longum and B. infantis were determined by using 19 strains related to these species, as determined by the numerical analysis. The degree of DNA binding was determined by the S1 nuclease method. The phenotypic study revealed that there were six main clusters, which were subdivided into nine subclusters. Subcluster Va contained the type strains of B. longum and B. infantis. The DNA-DNA relatedness values of some of the new isolates were very similar to the DNA-DNA relatedness values of the type strain of B. longum. On the basis of these data, it was difficult to isolate B. infantis strains and then to define B. infantis as a single species separated from B. longum. Subclusters IVb to IVf comprised reference strains of B. breve. Cluster III and subcluster Ia were not identified. PMID- 8347515 TI - Mycoplasma corogypsi sp. nov., a new species from the footpad abscess of a black vulture, Coragyps atratus. AB - Strain BV1 was isolated from the exudate of the footpad abscess of a black vulture (Coragyps atratus). The colonies had a "fried-egg" appearance consistent with that of mycoplasmal species. Electron microscopic examination of the cells revealed irregular elongated or elliptical forms and smaller circular budding processes. Profuse growth was observed in Frey medium supplemented with 20% swine serum at 37 degrees C in a humidified atmosphere of 10% CO2 and air. Typical of mycoplasma, strain BV1 required sterol for growth and catabolized glucose but did not hydrolyze arginine or urea. The guanine-plus-cytosine content of the DNA was 28 mol%. The organism demonstrated the ability to hemolyze, absorb onto, and agglutinate the erythrocytes from several animal species. Strain BV1 was serologically unrelated by the growth inhibition test to previously established Mycoplasma, Acholeplasma, Entomoplasma, and Mesoplasma species, as well as to strains belonging to these genera but not identified to species level. Moreover, BV1 had a 16S rRNA gene with a nucleotide sequence distinct from reported sequences of other mycoplasmas. This organism represents a new species for which the name Mycoplasma corogypsi is proposed. Strain BV1 (ATCC 51148T) is the type strain of Mycoplasma corogypsi sp. nov. PMID- 8347516 TI - DNA relatedness between field isolates of Mycoplasma F38 group, the agent of contagious caprine pleuropneumonia, and strains of Mycoplasma capricolum. AB - DNA-DNA hybridization experiments were carried out in order to clarify the taxonomic relationships between the F38 group of caprine mycoplasmas, the established etiologic agents of classical contagious caprine pleuropneumonia, and Mycoplasma capricolum, an organism associated with septicemia, arthritis, and mastitis in goats and sheep. The taxonomic status of the F38 group has been uncertain, principally because of the serological, genomic, and other properties which it shares with M. capricolum. Tritium-labeled DNAs from the M. capricolum type strain (California kid) and from prototype strain F38 were hybridized with unlabeled DNAs from these two strains and from four other isolates belonging to each group. The results showed consistent DNA relatedness values of about 70% between the F38 and M. capricolum groups, compared with levels of relatedness of about 90 and 85%, respectively, for the strains within each group. In addition, the results of comparisons of these 10 strains in which growth inhibition and immunofluorescence tests were used confirmed the previously reported serological relationships between the two groups and reinforced other observations concerning their shared genomic and cell membrane characteristics, indicating that there is a close taxonomic relationship. However, as the 70% DNA relatedness values between the M. capricolum and F38 groups also indicate a degree of genomic difference inconsistent with a relationship at the species level, we conclude that our findings support previous proposals for classification of the F38 group as a subspecies of M. capricolum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347517 TI - Proposal for designation of F38-type caprine mycoplasmas as Mycoplasma capricolum subsp. capripneumoniae subsp. nov. and consequent obligatory relegation of strains currently classified as M. capricolum (Tully, Barile, Edward, Theodore, and Erno 1974) to an additional new subspecies, M. capricolum subsp. capricolum subsp. nov. AB - A subspecies relationship with the existing species Mycoplasma capricolum is appropriate for the F38 group of mycoplasmas, the causative agent of classical contagious caprine pleuropneumonia. We believe that this classification is justified on the basis of the close DNA-DNA relationship recently reported for isolates belonging to the two groups and the other known serological and biological similarities and differences of these organisms. Strain F38T (T = type strain) and taxonomically indistinguishable strains are therefore proposed as members of a new subspecies of M. capricolum, M. capricolum subsp. capripneumoniae. Strain F38 (= NCTC 10192) is the type strain of M. capricolum subsp. capripneumoniae subsp. nov. As a consequence of this subdivision of the species M. capricolum, strains previously classified as M. capricolum are now necessarily relegated to subspecies status, as M. capricolum subsp. capricolum subsp. nov. Strain California kid (= ATCC 27343 = NCTC 10154) is the type strain of M. capricolum, as well as of M. capricolum subsp. capricolum. A taxonomic description of M. capricolum subsp. capripneumoniae and a brief amended description of M. capricolum subsp. capricolum are presented. PMID- 8347518 TI - Stenotrophomonas, a new bacterial genus for Xanthomonas maltophilia (Hugh 1980) Swings et al. 1983. AB - In consideration of the criticisms of the transfer of Pseudomonas maltophilia to the genus Xanthomonas proposed by J. Swings, P. De Vos, M. Van den Mooter, and J. De Ley (Int. J. Syst. Bacteriol. 33:409-413, 1983), a new generic name is created for this taxon. The name Stenotrophomonas is here proposed for the new genus, which includes a single species, Stenotrophomonas maltophilia. This proposal restores the genus Xanthomonas to its former definition (J. Bradbury, p. 199-210, in N. R. Krieg and J. G. Holt, ed., Bergey's Manual of Systematic Bacteriology, 1984) The arguments on which this proposal is based are presented. PMID- 8347519 TI - Phylogenetic relationship of Chlamydia pneumoniae to Chlamydia psittaci and Chlamydia trachomatis as determined by analysis of 16S ribosomal DNA sequences. AB - The 16S ribosomal DNA sequence of Chlamydia pneumoniae was determined and compared with the corresponding gene sequences of Chlamydia psittaci and Chlamydia trachomatis. C. pneumoniae has been reported to exhibit little chromosomal DNA homology with the other chlamydial species, and its phylogenetic relationships within the genus Chlamydia have not been described. A polymerase chain reaction was employed to determine the 16S rRNA gene sequence of C. pneumoniae. Ten primers from the C. psittaci sequences were used to amplify a C. pneumoniae template in overlapping segments of the gene. Sequence data for 1,554 bases indicated that the levels of homology of C. pneumoniae with C. psittaci and C. trachomatis were 96.19 and 94.07%, respectively. These data support the results of previous biochemical and developmental studies indicating that C. pneumoniae is more closely related to C. psittaci than to C. trachomatis. PMID- 8347520 TI - Phylogenetic position of Taylorella equigenitalis determined by analysis of amplified 16S ribosomal DNA sequences. AB - The 16S ribosomal DNA sequence of Taylorella equigenitalis (formerly Haemophilus equigenitalis), the causative organism of contagious equine metritis, was determined. A phylogenetic analysis of this sequence revealed a phylogenetic position of T. equigenitalis in the beta subclass of the class Proteobacteria apart from the position of Haemophilus influenzae, which belongs to the gamma subclass of Proteobacteria. A close phylogenetic relationship among T. equigenitalis, Alcaligenes xylosoxidans, and Bordetella bronchiseptica was detected; Spirillum volutans and Chromobacterium fluviatile (Iodobacter fluviatile) were in the same group but slightly removed. This relationship is surprising in view of the considerable differences in the G + C contents of the genomes of these bacteria. PMID- 8347522 TI - [Bone marrow transplantation]. PMID- 8347521 TI - Evidence from Aeromonas for genetic crossing-over in ribosomal sequences. PMID- 8347523 TI - [Care of patients before, during and after bone marrow transplantation]. PMID- 8347524 TI - [Psychosocial care on oncology]. PMID- 8347525 TI - [Rooming-in--is it meaningful also for chronically ill children?]. PMID- 8347526 TI - [The doctrine of healing children]. PMID- 8347527 TI - [Total parenteral nutrition of premature and newborn infants]. PMID- 8347528 TI - [New rules for education for the health care and nursing professions in Switzerland]. PMID- 8347529 TI - ["The Einbeck recommendations"--the revised "Einbeck recommendations" give advice as to the limits of obligation to medical treatment of severely disabled newborn infants]. PMID- 8347530 TI - [Poisonous and less poisonous plants. 8. Golden Rain (Laburnum anagyroides)]. PMID- 8347532 TI - [The registered association Sterntaler--for the support of the department of pediatric surgery at the Johannes Gutenberg University in Mainz]. PMID- 8347533 TI - Setting a standard. PMID- 8347531 TI - [Carl Gerhardt (1833-1902)]. PMID- 8347534 TI - Phase I/II study of concurrent weekly carboplatin and radiation therapy in advanced head and neck cancer. AB - Thirty-two patients with locally advanced head and neck cancer have been treated with concurrent weekly carboplatin and conventional radiation therapy (RT) (2 Gy fractions 4-5 days/week to a total dose of 64-70 Gy over 7-8 weeks) in a Phase I/II study. Carboplatin was administered weekly during RT at doses of 75-150 mg/m2/wk as a 1-hour infusion. The maximum tolerated dose of carboplatin was 130 mg/m2/wk, with myelosuppression, predominantly neutropenia, being dose limiting. Other systemic toxicities were insignificant and no overlapping toxicity was evident. Ultimate locoregional control and survival probabilities were disappointing. It is suggested that either further studies using radiation and carboplatin at the dose 130 mg/m2/wk, or variations on dose and scheduling be performed prior to the instigation of Phase III studies. PMID- 8347535 TI - Multiple fractions daily for head and neck cancer: spinal cord effects and other late results. AB - Reports of late spinal cord damage after multiple fractions daily radiotherapy regimens for head and neck cancer are infrequent, but increasing. We have reviewed our experience of head and neck cancers treated thrice daily to examine this problem. Between 1982 and 1990, 65 patients with advanced head and neck cancer were treated by primary radiotherapy using three small fractions delivered on 5 days per week, with an inter-fraction interval of 3-4 hours during normal working hours. In 25 patients, the cervical spinal cord received > 39 Gy. In 13 patients, 39.6 Gy was given in 1.1 Gy fractions, and five received 41.8 Gy in 1.1 Gy fractions, two received 45.1 Gy in 1.1 Gy fractions and five received 45 Gy in 1.5 Gy fractions. Eleven of these patients have survived over 2 years, and can be assessed for late spinal cord damage. Ten of these received 1.1 Gy fractions with no cord damage. The only 2-year survivor whose cord received 45 Gy in 1.5 Gy fractions has developed mild, non-progressive long tract signs. Other late side effects were equivalent to those after conventionally fractionated radiotherapy. Tumour control was good, especially for the larynx. We feel that, for radiotherapy given with three small fractions daily and an inter-fraction interval of 3-4 hours, the spinal dose should not exceed 40 Gy. PMID- 8347536 TI - Primary radiotherapy for subglottic carcinoma. AB - Between 1976 and 1990, 23 patients with subglottic carcinoma of the larynx were treated by one radiotherapist; these were reviewed. Primary radiotherapy was given using small parallel opposed wedged fields to the neck. No mediastinal radiotherapy was used. Mean follow up was 67 (9-165) months. Actuarial analysis showed a 2-year overall survival of 69.0% (78.3% excluding intercurrent deaths), and a 2-year disease free survival of 68.6%. Failure was due to persistent disease (5 patients) or recurrence (2 patients, both with disease T3, salvaged by surgery at 5 and 20 months). No patient developed clinical mediastinal relapse. These better than expected results support the use of primary radiotherapy to the neck alone avoiding conventional mediastinal radiotherapy. A national questionnaire sent to 67 consultant otolaryngologists sought information on perceived incidence, cure rate, and preferred mode of treatment and produced a 67% response rate. The results confirmed our belief that surgeons have a pessimistic perception of the value of radiotherapy in this condition. PMID- 8347537 TI - Incidence and survival of malignant parotid tumours in the West Midlands region 1977-1986. AB - The aim of this study was to describe the incidence and survival of patients with malignant parotid tumours resident in the West Midlands Regional Health Authority. The study population consisted of all patients with malignant tumours arising in the parotid gland and registered with the West Midlands Regional Cancer Registry between 1 January 1977 and 31 December 1986. Variables included in the analysis were: age, sex, date of diagnosis, side of origin, tumour histology, vital status and date of death. No temporal change in the incidence of parotid tumours was observed. More tumours originated within the left parotid gland (chi 2(1) = 4.0, P < 0.05). The 5-year actuarial survival for all tumours was 55.7%. When a Cox's proportional hazards regression model was fitted to the data, age at diagnosis (60-74 years) and histological type were found to be the critical determinants of outcome. PMID- 8347538 TI - Phase I study of hyperfractionated whole brain irradiation (HWBI) in the treatment of primary cerebral lymphoma. AB - The poor prognosis for primary cerebral lymphoma following conventional radiation therapy has generally been attributed to high local relapse rates despite initial local control. Hyperfractionated radiation therapy may improve the therapeutic ratio by allowing higher total radiation doses to be prescribed without exceeding the radiation tolerance of the central nervous system (CNS). Eight patients entered a study of hyperfractionated whole brain irradiation (HWBI) between October 1988 and May 1991. The prescribed dose was 64.8 Gy in 54 fractions over 5.5 weeks. All patients were followed clinically and with computed tomographic scanning. Additional investigations to discriminate between lymphoma recurrence and radionecrosis included magnetic resonance imaging (MRI), thallium-201 single photon emission computed tomography (SPECT), and immunocytological examination of the cerebrospinal fluid (CSF). A complete remission as seen on CT scan was achieved in all cases. The overall median survival was 102 weeks. Six patients initially deteriorated neurologically without evidence of tumour recurrence. Three patients have died without evidence of recurrence at 18, 62 and 128 weeks. As of 31 May 1992, three patients remain alive, two with radiation brain injury at 147 and 184 weeks. Treatment toxicity prompted study closure in September 1991. The hyperfractionation regimen used is reported by others to be free from significant morbidity. The pathogenesis of cerebral lymphomas (diffuse disease, angiotropism, subependymal involvement) may adversely affect CNS radiation tolerance. PMID- 8347539 TI - A phase II evaluation of human lymphoblastoid interferon (Wellferon) in relapsed high grade malignant glioma. Medical Research Council Brain Tumour Working Party. AB - During the 1980s a number of studies suggested there might be a role for interferon in the treatment of high grade gliomas. In the light of these reports a formal Phase II evaluation of human lymphoblastoid interferon (Wellferon) was undertaken in patients with high grade gliomas which had relapsed after conventional radiotherapy; 14 patients were treated and no objective clinical responses were seen. This indicates that the overall response rate to interferon therapy in this situation would be less than 20%. It is therefore concluded that interferon administration is unlikely to be of value in the management of relapsed high grade gliomas. PMID- 8347540 TI - Pelvic radiotherapy with concurrent 5-fluorouracil modulated by leucovorin for rectal cancer: a phase II study. AB - Combined modality treatment for cancer of the rectum has been shown to reduce recurrences and improve overall survival. We wished to find out if we could safely give concurrent radiotherapy and 5-fluorouracil (5-FU) modulated by leucovorin (LV) in 3 settings: pre-operatively, adjuvantly and in recurrent disease. A total of 39 patients were treated, 11 preoperatively, 17 adjuvantly and 11 with recurrent disease. There were 26 males and 13 females with a median age of 64 years. The median radiotherapy (RT) dose was 45 Gy/25 fractions/1.8 Gy per fraction (range 25-63 Gy). Chemotherapy consisted of LV 80 mg/m2 i.v. infusion over 1.5 hours followed by 5-FU 400 mg/m2 i.v. bolus, both given once a week. The median number of cycles was 8 (range 3-12). Diarrhoea was the main toxicity, and was encountered in 30 patients (77%): grade 1 in 3 (8%), grade 2 in 12 (30%), grade 3 in 11 (28%), and grade 4 in 4 (10%). This required 18 (46%) patients to have modifications to their RT (20% had breaks and 26% ceased at doses < 45 Gy). Nine patients (23%) had modifications in the chemotherapy (10% had breaks and 13% received < 6 cycles). Encouraging responses were seen in the preoperative setting. Concurrent RT and 5-FU/LV, as given in this schedule, results in an unacceptable incidence of diarrhoea, limiting both the total dose of RT and chemotherapy that can be delivered, particularly in patients who have had previous surgery. PMID- 8347541 TI - Follow-up in stage I cutaneous malignant melanoma: an audit. AB - In Southampton, follow-up of patients with malignant melanoma is carried out in a single dedicated clinic. An audit has been performed to assess its objective value in diagnosing and treating tumour relapse and its subjective value as perceived by patients. Over a 10-year period, of 331 patients with Stage I disease 65 (20%) have developed tumour recurrence. Fifty-five first relapses were either local or in regional lymph nodes, and thus potentially curable; half were found within 3 months of the previous clinic visit. Seventy-two per cent of local and 47% of nodal recurrences were either symptomatic or detected initially by the patient. Whilst doctor-diagnosed nodal recurrences tended to be smaller and to involve fewer histologically positive nodes, subsequent survival was identical in those with patient-diagnosed nodal recurrences. The clinic makes inefficient use of medical time. Questionnaire responses indicate that 54% of patients suffer anxiety prior to clinic visits. Nevertheless follow-up was considered worthwhile by 95% of patients and regular visits were preferred to a 'walk in when necessary' system. The clinic appears to have an important educational role. A series of changes to current follow-up practice are proposed including: more frequent visits for high risk patients, changes in clinic personnel, and greater emphasis on patient education and self examination. PMID- 8347542 TI - Pneumothorax as a complication of tumour response to chemotherapy. AB - A patient with extensive pulmonary involvement by disseminated adenocarcinoma is presented. Response to chemotherapy resulted in the direct rupture of necrotic tumour tissue into the pleural cavity leading to a pneumothorax. The condition failed to improve with chest drainage and suction, necessitating surgical intervention. The development of the pneumothorax proved to be a fatal complication of treatment. PMID- 8347543 TI - Testicular seminoma metastasizing to palatine tonsil. AB - Patients presenting with Stage I seminoma of the testis have an excellent prognosis after treatment by orchidectomy and prophylactic radiotherapy to the paraaortic and pelvic lymph nodes. Only 2% subsequently recur but relapse in these cases has been reported in unusual sites such as the prostate and mesentery. We report a case of Stage I seminoma relapsing in another rare site for secondary malignant deposits, the palatine tonsil. This case further illustrates the favourable prognosis for this tumour even in cases of distant recurrence. PMID- 8347544 TI - Vertebral haemangioma presenting as Kasabach-Merritt syndrome. AB - A case of spinal cord compression due to vertebral haemangioma is described as presenting as part of the Kasabach-Merritt syndrome, which is characterized by bleeding disorder, thrombocytopenia and leukopenia. A dramatic improvement in neurological status and coagulation profile following surgical decompression and postoperative radiotherapy is reported. A brief review of the literature on the usefulness of radiotherapy is discussed. PMID- 8347545 TI - Non-Hodgkin's lymphoma: an unusual cause of myocardial infarction and hypercalcaemia. AB - Cardiac involvement is reported in 10%-20% of patients with lymphoma, but it is characteristically difficult to detect clinically or by investigation. Hypercalcaemia is a rare complication. Both complications usually occur late in the natural history of lymphoma. We report a case of non-Hodgkin's lymphoma, who, within 2 weeks of presentation, developed symptomatic hypercalcaemia and, 3 days later, died of an acute myocardial infarction. Autopsy showed, unexpectedly, the unusual finding of coronary artery compression by lymphomatous deposits. PMID- 8347547 TI - Strive to keep alive? PMID- 8347546 TI - The interaction of cisplatin and radiotherapy. PMID- 8347548 TI - Perception of transparency in stationary and moving images. AB - If two neutral density (ND) filters overlap partially, the luminance of the overlapping region is given by a multiplicative relationship (e.g., if the filters have 50% transmittance then on a 100 cd m-2 background, the luminance of each filter would be 50 cd m-2 but the luminance of the overlapping region would be 50% of 50 cd m-2, i.e. 25 cd m-2). Does the visual system respect this relationship? Two grey rectangles were overlapped to form a 'cross' and the luminance of the intersection was randomly varied. Naive subjects' ratings of transparency showed a surprising consistency with physics. A similar relationship is seen if two moving square-wave gratings are superimposed. When the intersection luminances were close to the multiplicative (25 cd m-2) case, component motion was seen, and values less than 25 cd m-2 and higher than 50 cd m 2 caused a decline in perceived component motion. Two interpretations are offered. (a) The visual system has access to 'tacit knowledge' of transparency and shadows. (b) If you assume a log signal compression in the retina, then by multiplying the luminances you would null the Fourier energy from the 'blobs' (i.e. regions of overlap between the two gratings). This would prevent 'blob tracking' and lead to the perception of coherent motion. Since most researchers in the field had simply added the gratings linearly they would have inadvertently introduced extra Fourier energy in the blobs and this might account for all previous instances of coherent motion observed in such displays. Whatever the ultimate interpretation, the present results provide the first clear evidence that even the processing of certain primitive visual dimensions--such as motion- can be powerfully constrained by the perception of transparency (Ramachandran V. S. (1990) in: AI and the Eye, Wiley, Chichester; Stoner, G., Albright, T. and Ramachandran, V. S. (1990) Nature 344, 153-155). This is well in line with other recent results demonstrating that transparency can also constrain the processing of stereopsis (Nakayama, K., Shimojo, S. and Ramachandran, V. S. (1991) Perception 19, 497-513) and perceptual grouping (Ramachandran, V. S. (1990) in: AI and the Eye, Wiley, Chichester). PMID- 8347550 TI - The interaction of luminance, velocity, and shape information in the perception of motion transparency, coherence, and non-rigid motion. AB - The perception of luminance transparency for superimposed patterns depends on how luminance, figural, and topological conditions are simultaneously satisfied. Motion transparency or coherence for two superimposed patterns, which correspond to the perception of both patterns moving across one another or to the perception of compound motion of the regions of pattern intersection, depends on the relation between the local velocity, luminance, and shape information. This study analyzes how luminance, shape, and local velocity interact in the perception of motion transparency and coherence. Psychophysical experiments done with sinusoidally modulated bar patterns are presented which show that the perception of motion transparency or coherence can be described as the result of the interaction of two integration modules: the velocity-luminance and the velocity shape processes. The velocity-luminance process describes the integration of the local velocity with luminance information. When the luminance transparency rules are satisfied this process always generates the perception of motion transparency independently of the shape or contour information. On the other hand, when the luminance transparency rules are violated one can either perceive motion coherence or non-rigid motion; one perceives motion coherence when the patterns have small or zero amplitude, and non-rigid motion when the patterns have large amplitude. The velocity-shape process describes the integration of local velocity with shape information, and this depends on the relation between the error in the extraction of the local velocity and the magnitude of the contour amplitude. As a result of these experiments it is conjectured that the velocity-luminance and the velocity-shape processes do interact constructively or destructively. The constructive interaction occurs when the luminance transparency rules are satisfied. The destructive interaction occurs when the luminance transparency rules are violated, and such that, although the patterns contain sufficient shape information to solve the aperture problem and therefore generate the perception of motion transparency, one perceives non-rigid motion. This shows that global information describing the stratification of superimposed patterns can affect the integration of local velocity information with, for example, shape information, and this is not described by current motion theories. PMID- 8347549 TI - The role of early mechanisms in motion transparency and coherence. AB - Perceptual dissociation of moving plaid patterns into independently moving bar gratings occurs most readily when the grating signals are combined as if the bars were semi-transparent objects (Ramachandran, V. S. (1990) in: AI and the Eye. Wiley, Chichester, pp. 21-77. Stoner, G. R., Albright, T. D. and Ramachandran, V. S. (1990) Nature 344, 153-155). These and other examples of motion transparency are exploited to constrain the set of viable models for human motion processing. For example, one may exclude any fixed recombination of local motion signals into a plaid motion signal. Broad classes of linear and non-linear mechanisms for tracking blobs, corners, and other unambiguous plaid motion cues can also be ruled out because they fail to reproduce the experimental results even qualitatively. The shifting balance between the 'coherent plaid' and 'sliding gratings' percepts are attributed to processing stages before any integration or combination of local motion signals. The first essential stage is a roughly logarithmic nonlinearity before orientation filtering. In general, the resulting cross-products (at the intersections) code unambiguously for the true plaid motion vector, but these signals will be nulled for multiplicatively combined plaid components. Supporting evidence for this idea is obtained in our measurements of detection thresholds for the 'plaid' and 'sliding' percepts. The essential element of the second stage consists of 'end-stop' cells which detect the nullable intersection signal, and so produce a plaid-motion signal with the required characteristics. Finally, it is argued that the ecological role of the proposed mechanism lies in the ability to handle movement of patterned objects in lighting conditions dominated by complicated cast shadows. PMID- 8347551 TI - The computation of multiple matching doubly ambiguous stereograms with transparent planes. AB - Psychophysical experiments have been previously described Weinshall, D. (1989) Nature 341, 737-739; (1991) Vision Research 31, 1731-1748 that involved the perception of many transparent layers, corresponding to multiple matching, in doubly ambiguous random-dot stereograms. Additional experiments are described in the first part of this paper. In one experiment, subjects were required to report the density of dots on each transparent layer. In another experiment, the minimal density of dots on each layer, which is required for the subjects to perceive it as a distinct transparent layer, was measured. The difficulties encountered by stereo matching algorithms, when applied to doubly ambiguous stereograms, are described in the second part of this paper. Algorithms that can be modified to perform consistently with human perception, and the constraints imposed on their parameters by human perception, are discussed. PMID- 8347552 TI - Surface decomposition accompanying the perception of transparency. AB - At the retina, each location can have only one value of luminance or color. When transparency is perceived, however, different surface qualities can be redistributed to two or more apparently superimposed layers. The experiments described here explored the characteristics of this surface decomposition. It is shown that the surface decomposition occurs rapidly, it affects even early stages of visual processing, and it involves attributes such as texture and motion as well as color and brightness. In the first experiment, the recognition advantage for transparent overlapping digits demonstrated that the surface decomposition accompanying transparency occurs within 60 ms. In the second, the separation of overlying orthogonal grids due to surface decomposition was found to influence the strength of the McCollough effect, an effect attributed to early cortical processing. Finally, when a transparent surface appears to extend over areas that are physically identical to the background, qualities of the transparent overlay such as texture and motion, as well as color or brightness (e.g., the neon color effect) appear to spread to the illusory overlay. PMID- 8347553 TI - Analysis of somatic mutation activity in multiple V kappa genes involved in the response to 2-phenyl-5-oxazolone. AB - We have studied somatic mutation activity early in a response to 2-phenyl-5 oxazolone coupled to ovalbumin (phOx-OVA). Although the V kappa Ox1 gene rearranged to J kappa 5 is known to predominate in this response, other closely related V kappa genes are involved. We compared the introduction of point mutations into V kappa Ox1 genes and into a set of related V kappa genes rearranged to the same J kappa segment at two time points after primary immunization. The result showed that quantitation of mutations in a single rearrangement substrate leads to an underestimation of the total mutational activity. There is pronounced somatic mutation activity early within genes that may be absent later in the response. We also show that multiple somatic mutations can be detected in B cells from draining lymph nodes after foot-pad injection with phOx-OVA already at day 7 after immunization. The data suggest a system in which mutation acts early in the response on a wide range of substrates and that selection and expansion of high affinity paratopes occurs later. PMID- 8347554 TI - V region dependent selection of persistent resting peripheral B cells in normal mice. AB - In this study, we compare the VH gene family repertoire of persistent long-lived splenic B cells with that of the whole splenic B cell compartment. Persistent long-lived B cells were obtained by two independent strategies. Firstly, we studied cells that persist in the peripheral pools with or without cell division. We have transferred mature lipopolysaccharide (LPS)-reactive splenic B cells into LPS non-responder recipients and studied the donor population that could be recovered in host mice at differing time intervals after cell transfer. Secondly, we studied non-cycling resting long-lived B cells. These cells were obtained in normal mice after cytostatic treatment with hydroxyurea and in mice transgenic for the HSV-1 thymidine kinase gene after treatment with the anti-herpetic ganciclovir. Studying the VH gene family usage at the single level by in situ hybridization, we found that persistent B cells show an increased expression of the VHJ558 family and a diminished representation of the VH7183 family. These results demonstrate that in a normal non-immunized mouse, B cell survival and persistence in the resting state results from V region dependent selection. PMID- 8347555 TI - The immunoaugmenting properties of murine IgD reside in its C delta 1 and C delta 3 regions: potential role for IgD-associated glycans. AB - IgD receptor (IgD-R) bearing CD4+ T cells with immunoaugmenting properties in vivo are induced in mice within 24 h after a single injection of dimeric or aggregated IgD. In the present study, we sought to identify the region(s) of IgD responsible for upregulation of IgD-R and for the immunoaugmenting effect of IgD. IgD-R can be upregulated on CD4+ T cells in vitro and in vivo by glutaraldehyde aggregated mutant IgD or by fragments of enzymatically digested IgD molecules possessing either the C delta 1 domain (Fd delta) or the C delta 3 domain (Fc delta). Neoglycoproteins (D-galactose--BSA and N-acetyl-D-glucosamine--BSA), can competitively block upregulation of IgD-R by IgD in vitro. Furthermore, when injected 1 day before antigen, the aggregated IgD derived molecules, KWD1 (which lacks C delta 1), KWD6 (which lacks C delta 1 plus C delta-hinge), and Fab delta can all cause augmentation of antigen-specific primary and secondary antibody responses comparable to that achieved with intact aggregated IgD. Moreover, the immunoaugmenting effect of intact oligomeric IgD molecules in primary antibody responses is competitively blocked by simultaneous injection of monomeric forms of KWD6 and Fab delta. These results suggest that the binding of IgD to IgD-R, previously shown to be dependent on N-glycans present on Fd delta and Fc delta regions, also contributes to the upregulation of IgD-R and immunoagumentation. PMID- 8347556 TI - Functional and morphological characterization of 4F7+ spleen accessory dendritic cells. AB - Recently we have reported on the production of the mAb 4F7. This recognizes a molecule that is upregulated on dermal and epidermal dendritic cells after application of contact allergen. Furthermore, this antibody detects an antigen on spleen and lymph node dendritic cells. In this study, we characterize 4F7+ spleen dendritic cells and show that the mAb recognizes in situ few labeled cells in the white pulp of the spleen and approximately 1% of spleen single cell suspensions as evidenced by cell enrichment, immunoperoxidase staining and FACS analysis. Immunohistological characterization of the cells with mAbs revealed the expression of class II, class I MHC antigens, 33D1, CD11c, ICAM-1, and CD45 molecules. After enrichment and cultivation for approximately 3 days, these cells showed no adherent properties. The capacity of 4F7+ spleen dendritic cells to activate allogeneic T cells in the primary mixed lymphocyte reaction was similar to freshly isolated Ia+ Langerhans cells. With regard to the induction of a proliferative response of CD4+ naive T cells that were incubated with concanavalin A or anti-CD3 mAb, 4F7+ spleen dendritic cells were two to three times more potent than spleen microphages and B cells. Furthermore, 4F7+ cells efficiently stimulated the antigen dependent proliferation of a T helper cell line. The mAb 4F7 will be useful for the purification of dendritic cells and for functional and molecular biological studies. PMID- 8347557 TI - MHC class II molecules bind indiscriminately self and non-self peptide homologs: effect on the immunogenicity of non-self peptides. AB - Synthetic peptides spanning the entire sequence of both human and mouse beta 2 microglobulin (beta 2M) have been tested for their capacity to bind to three different mouse (I-Ad, I-Ed, and I-Ak) or human (DR1, DR2, and DR5) class II molecules. The results demonstrate that class II molecules do not discriminate between self and non-self peptides. When the immunogenicity of the human beta 2M peptides was measured by their ability to prime H-2d mice for in vitro T cell proliferation, it was found that peptides incapable of binding class II molecules in vitro were also non-immunogenic in vivo. Interestingly, however, several binders, including the human beta 2M peptide 1-16, the best binder in this series to Iad molecules, were found to be non-immunogenic. Since the corresponding mouse beta 2M peptide 1-16 was also capable of binding to Iad molecules, this suggested that lack of responsiveness to the non-self peptide could arise either from central or peripheral tolerance induced by the self homolog. Alternatively, lack of responsiveness could arise from other mechanisms, such as negative selection by other non-homolog sequences or lack of suitable T cell receptor genes. To discriminate between these possibilities, H-2d mice with disrupted beta 2M genes were immunized with the human beta 2M peptide 1-16. This peptide also failed to prime for T cell responsiveness in beta 2M-negative mice, suggesting that a hole in the T cell repertoire for this antigen was not mediated by negative selection or peripheral tolerance induced by self beta 2M peptides. PMID- 8347558 TI - Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. AB - B lymphocyte differentiation is characterized by an ordered series of Ig gene assembly and expression events. In the majority of normal B cells, assembly and expression of Ig heavy (H) chain genes precedes that of light (L) chain genes. To determine the role of the Ig heavy chain protein in B cell development and L chain gene rearrangement, we have generated mice that cannot assemble Ig H chain genes as a result of targeted deletion of the JH gene segments in embryonic stem cells. Mice homozygous for this deletion are devoid of slg+ B cells in the bone marrow and periphery. B cell differentiation in these mice is blocked at the large, CD43+ precursor stage. However, these precursor B cells do assemble kappa L chain genes at a low level in the absence of mu H chain proteins. These data demonstrate that rearrangement and expression of the mu H chain gene is not absolutely required for kappa L chain gene rearrangement in vivo. Expression of mu chains may facilitate either efficient L chain gene rearrangement or the survival of cells that have rearranged light chain genes by promoting the differentiation of large, CD43+ to small, CD43- pre-B cells. PMID- 8347559 TI - Expression of recombinant rabbit IL-8 in Escherichia coli and establishment of the essential involvement of IL-8 in recruiting neutrophils into lipopolysaccharide-induced inflammatory site of rabbit skin. AB - In order to establish the pathophysiological roles of IL-8, rabbit IL-8 was expressed in Escherichia coli and purified to homogeneity by sequential chromatography on heparin agarose, CM-HPLC, and RP-HPLC. The purified recombinant rabbit IL-8 was homogeneous on SDS-PAGE and the ED50 of neutrophil chemotactic activity for rabbit peritoneal neutrophils was 2 ng/ml. The binding of 125I labeled rabbit IL-8 to rabbit neutrophils was inhibited by unlabeled human IL-8 as well as rabbit IL-8 but not by another leucocyte chemotactic cytokine (chemokine), monocyte chemotactic and activating factor. Scatchard plot analysis of the binding of 125I-labeled rabbit IL-8 to rabbit peritoneal neutrophils revealed that the rabbit neutrophils have two affinity classes of receptors for IL-8 (Kd = 2.3 nM, 4.1 x 10(4) sites/cell; Kd = 18.0 nM, 11.4 x 10(4) sites/cell). It was found that a previously generated mouse anti-human IL-8 mAb, WS-4, inhibited the binding of 125I-labeled rabbit IL-8 to rabbit neutrophils, and blocked neutrophil chemotaxis in vitro in a specific and dose-dependent manner. An ELISA system for rabbit IL-8 was established using this mAb and guinea pig polyclonal antibodies to recombinant rabbit IL-8 to measure the levels of IL 8 in rabbit plasma. Intravenous administration of lipopolysaccharide (LPS) (100 micrograms) in rabbits caused the highest level of IL-8 in blood at around 2 h. Intravenous administration of WS-4 (10 mg) inhibited neutrophil infiltration at the site of LPS injection into the rabbit skin, suggesting that IL-8 is essential in the recruitment of neutrophils at sites of acute inflammation in vivo. PMID- 8347560 TI - Rapid acceleration of neutrophil apoptosis by tumor necrosis factor-alpha. AB - We demonstrate here that human necrosis factor-alpha, a potent neutrophil activator, induces rapid (within 3 h) apoptosis of these cells, i.e. neutrophils treated with this cytokine exhibit (i) light and electron microscopic changes characteristic to apoptotic cells, (ii) reduced propidium iodide binding to DNA, and (iii) the ladder form of DNA, as shown by agarose gel electrophoresis. These results suggest that apoptosis acceleration may be involved in processes by which neutrophils are prevented from damaging tissues. PMID- 8347561 TI - Mouse CD4 binds MHC class II with extremely low affinity. AB - Interaction of CD4 with MHC class II molecules plays a crucial role during thymic development and activation of single-positive CD4 T lymphocytes. The quantitation of this interaction is, therefore, important for understanding the role of CD4 during these events. To this end, we have developed a rosette assay, which enabled us to study this molecular interaction. By coupling soluble mouse CD4 onto beads, we could show specific binding of CD4 to MHC class II molecules on A20 B lymphoma cells. These binding studies revealed an extremely low affinity (Ka < or = 10(4) M-1) between CD4 and MHC class II molecules in mouse. PMID- 8347562 TI - MOUSE: a teachable program for learning in conformational analysis. AB - MOUSE is a teachable program which learns concepts of conformational analysis from examples obtained from WIZARD. The algorithms are presented, and a fully worked example is used to demonstrate how MOUSE learns about the so-called "pentane rule." PMID- 8347563 TI - Short-term learning in conformational analysis. AB - A method for learning short-term rules of conformational analysis is introduced. The technique works by discovering problems during the building of a conformation in Cartesian coordinate space, and builds an abstract critic suitable for reasoning in abstract symbolic space. The methods not only afford speed increases ranging from 1.0- to 2.3-fold in WIZARD (analysis completed in 100% to 43% of original run time), but can be modified to provide similar increases in other programs that use "template joining" and distance geometry. These methods also provide the basis for a long-term learning project. PMID- 8347564 TI - Cooperative effects in the transport of small molecules through an amorphous polymer matrix. AB - The transport of small molecules (penetrants) through polymer materials proceeds by a hopping mechanism: A penetrant typically dwells in a cavity of the polymer for a while and then performs a quick jump into an adjacent cavity. In this article we investigate a jump event in detail. Molecular graphics is used to identify if and how the motion of the penetrant is aided by the fluctuations of the polymer matrix. We employ both traditional molecular graphics techniques to show atomic motion and surface rendering methods to display the redistribution of penetrant-accessible volume in the polymer. PMID- 8347565 TI - A note on the low-dimensional display of multivariate data using neural networks. AB - A novel neural network technique has been proposed (Livingstone et al. J. Mol. Graphics 1991, 9, 115-118) which is useful for a low-dimensional display of multivariate data sets. The method makes use of the activity values of the hidden neurons in a trained three-layer feed-forward network to produce the low dimensional display. It was claimed that in contrast to conventional techniques, such as principal components analysis or nonlinear mapping, this technique could be used also to reconstruct, from a given point in the low-dimensional display, the corresponding multivariate input vector via the completely known weight matrices of a suitably trained network. We show here that this claim is unjustified in this general form. When previously unknown, grossly different input vectors are presented to the trained network, they can occupy, for example, exactly the same point in the low-dimensional display which is occupied also by a given training vector, if certain linear relationships between the vector components are fulfilled. Thus, an infinite set of different linearly dependent input vectors is projected onto one single point in the low-dimensional display. Reconstruction of a multivariate vector, starting from this point in the low dimensional display, is able to lead back to only one multivariate vector (in the example given, to the original training vector). PMID- 8347566 TI - SETOR: hardware-lighted three-dimensional solid model representations of macromolecules. AB - SETOR is designed to exploit the hardware lighting capabilities of the IRIS-4D series graphics workstations to render high-quality raster images of macromolecules that can undergo rotation and translation interactively. SETOR can render standard all-atom and backbone models of proteins or nucleic acids, but focuses on displaying protein molecules by highlighting elements of secondary structure. The program has a very friendly user interface that minimizes the number of input files by allowing the user to interactively edit parameters, such as colors, lighting coefficients, and descriptions of secondary structure via mouse activated dialogue boxes. The choice of polymer chain representation can be varied from standard vector models and van der Waal models, to a B-spline fit of polymer backbones that yields a smooth ribbon that approximates the polymer chain, to strict Cardinal splines that interpolate the smoothest curve possible that will precisely follow the polymer chain. The program provides a photograph mode, save/restore facilities, and efficient generation of symmetry-related molecules and packing diagrams. Additionally, SETOR is designed to accept commands and model coordinates from the standard input stream, and to control standard output. Ancillary programs provide a method to interactively edit hardcopy plots of all vector and many solid models generated by SETOR, and to produce standard HPGL or PostScript files. Examples of figures rendered by SETOR of a number of macromolecules of various classes are presented. PMID- 8347567 TI - The molecular surface package. AB - The Molecular Surface Package is a reimplementation, in C, of a set of earlier FORTRAN programs for computing analytical molecular surfaces, areas, volumes, polyhedral molecular surfaces, and surface curvatures. The software does not do interactive molecular graphics, but it will produce pixel maps of smooth molecular surfaces. The polyhedral molecular surfaces are suited to display on graphics systems with real-time rendering of polyhedra. PMID- 8347568 TI - Modeling and solution structure probing of the HIV-1 TAR stem-loop. AB - We present a model for the three-dimensional structure of the HIV TAR stem-loop, based on a modeling algorithm which makes use of the known X-ray coordinates of tRNAs to generate a model structure, which has then been tested experimentally in solution by enzymatic and chemical structure probing of ribo-oligonucleotides encompassing the TAR sequence. The modeling suggested that the structure of TAR was similar to that of the anti-codon loop of tRNA(Asp), having a loop of just three single-stranded residues with a mismatched adenine excluded from the helical stem on the 3' side of the loop. The structural probing is consistent with such a structure for the loop, and reveals an unusual structure around the 5' uridine-rich bulge, which is the binding target for the transactivator protein Tat. These data may be useful in understanding the interaction of TAR with the Tat protein and may aid in the design of anti-AIDS drugs. The coordinates of the model are available on request. PMID- 8347569 TI - Molecular surface comparison: application to drug design. AB - An interactive system for the display and manipulation of molecular surface properties is presented. The property at the molecular surface is mapped onto the sphere by gnomonic projection. This representation allows direct comparison of the surface properties of pairs of molecules. The system allows the user to explore the similarities between a pair of molecules in an interactive manner, and provides extensive visual (color-coded field and field difference maps) and numerical (rms difference value) aids to complement the user's chemical intuition. Examples of the use of the system to study beta-lactam compounds and phosphodiesterase inhibitors are presented. PMID- 8347570 TI - Helix stop signals in proteins and peptides: the capping box. AB - The alpha-helix [Pauling, L., Corey, R. B., & Branson, H. R. (1951) Proc. Natl. Acad. Sci. U.S.A. 37, 205-211] is a common motif in both proteins and peptides. Despite intense investigation, predictive understanding of helices is still lacking. A recent hypothesis [Presta, L. G., & Rose, G. D. (1988) Science 240, 1632-1641] proposed that the structural specificity of helices resides, in part, in those residues that flank helix termini. If so, then signals that arrest helix propagation--i.e., helix stop signals--should be found among these flanking residues. Evidence is presented for the existence of one such signal, a reciprocal backbone-side-chain hydrogen-bonding interaction, dubbed the capping box. In proteins, the capping box is found uniquely at helix N-termini. In peptides, the capping box can function as a helix stop signal, as shown in the work of Kallenbach and co-workers. PMID- 8347571 TI - A highly sensitive probe for guanine N7 in folded structures of RNA: application to tRNA(Phe) and Tetrahymena group I intron. AB - A nickel complex has been shown to promote conformation-specific oxidation of guanosine in polynucleotide RNA. In all cases, reaction was strictly dependent on the solvent exposure and surface properties of guanine N7. Modification of native tRNA(Phe) (yeast) was detected at G18, G19, G20, and Gm34 and concurred with predictions based on its crystal structure. Additional guanine derivatives became exposed to oxidation only after the tRNA unfolded in the absence of Mg2+. Reaction of the Tetrahymena group I intron RNA (L-21 ScaI) also compared favorably to its three-dimensional model by appropriately identifying guanosine residues in hairpin loops, duplex termini, and the essential cofactor binding site. These results complemented prior data generated by hydroxyl radical, and in combination they served to distinguish the solvent accessibility of sugar backbone and base positions in guanosine residues. Most importantly, this nickel complex exhibited greater selectivity than either dimethyl sulfate or RNase T1 for characterizing tRNA(Phe) and intron RNA. PMID- 8347572 TI - Expression of CheA fragments which define domains encoding kinase, phosphotransfer, and CheY binding activities. AB - The histidine protein kinase CheA is a central component of the Escherichia coli chemotaxis system. The autophosphorylation activity of CheA is controlled by membrane-bound chemoreceptors and by the CheW coupling protein. CheA phosphorylates the CheY and CheB proteins which respectively control the direction of flagellar rotation and the level of receptor adaptation, thereby regulating the cells' chemotactic response. Genes encoding three polypeptide fragments of CheA were constructed and expressed in order to better define the functional organization of the wild-type protein. These fragments allowed the identification of regions of the protein responsible for CheY binding, phosphotransfer, and kinase activity. The kinase domain was expressed as a 30-kDa polypeptide corresponding to the central portion of the wild-type protein which contains sequences homologous to other histidine kinases. It was able to phosphorylate a 15-kDa amino-terminal phosphotransfer domain which was separately expressed and purified. This latter domain is capable of phosphotransfer to CheY despite the fact that it lacks the ability to stably bind CheY. CheY was immobilized to a dextran matrix through a single cysteine residue which was introduced into the protein at a position far removed from the active site. A stable binding site for CheY was mapped to a segment between the site of autophosphorylation and the kinase domain by using surface plasmon resonance to detect binding to the immobilized CheY. The region of the kinase which tightly binds the unphosphorylated substrate may play an important role in regulating the specificity of the signal transducing system. PMID- 8347573 TI - Ligand binding and slow structural changes in chlorocruorin from Spirographis spallanzanii. AB - Chlorocruorin is a cooperative respiratory pigment found in the blood of polychaete worms; its prosthetic group is a derivative of the iron protoporphyrin IX, in which the vinyl group at position 2 is substituted by a formyl group. The quaternary structure of chlorocruorins is complex: myoglobin-like subunits are grouped in tetramers and tetramers in dodecamers; 12 dodecamers are assembled in the 3500-kDa particle. Chlorocruorin from Spirographis spallanzanii displays the following overall functional properties: (i) the oxygen affinity is lower than in human hemoglobin, while that of CO is similar if not higher; (ii) the rates of combination with oxygen and carbon monoxide are low; and (iii) the off rate of oxygen is comparable to that of human hemoglobin, while the off rate of CO is 10 times smaller. When CO is partially photolyzed with a long and powerful light flash (70 microseconds), rebinding is biphasic as in mammalian hemoglobins; however, the slowest rate is faster than that observed by stopped flow, suggesting that the unliganded protein decays from the liganded high affinity state (R) to an intermediate state before reaching the low affinity (T) state. Oxygen binding was followed by stopped-flow and flash photolysis. While partial photolysis yields a fast, second-order time course, stopped-flow experiments yield slow, biphasic, and non-second-order time courses. This pattern of reactivity was attributed to a slow conformational transition(s) which is (are) rare limiting with oxygen, but not with CO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347574 TI - Epsilon BP, a beta-galactoside-binding animal lectin, recognizes IgE receptor (Fc epsilon RI) and activates mast cells. AB - IgE-binding protein (epsilon BP) was originally identified in rat basophilic leukemia (RBL) cells by virtue of its affinity for IgE. epsilon BP is now known to be a beta-galactoside-binding lectin containing an S-type carbohydrate recognition domain. It is identical to a macrophage surface antigen, Mac-2, and lectins designated as CBP35, L-34, and RL-29, for which various functions have been suggested. Studies from other groups as well as ours have indicated that epsilon BP is secreted by cells such as macrophages and is present in extracellular fluids. We demonstrated previously that binding sites for epsilon BP are present on the surface of RBL cells. In this report, we show that epsilon BP binds to a small number of glycoprotein species on the surface of RBL cells. Significantly, one of these glycoproteins is the high-affinity IgE receptor (Fc epsilon RI). Preliminary studies showed that epsilon BP causes mediator release from RBL cells, possibly through cross-linking of Fc epsilon RI. The results suggest a function of epsilon BP as an activator of mast cells. PMID- 8347575 TI - Effects of mutations in the hinge region of serpins. AB - An expression system for alpha 1-antitrypsin in Escherichia coli was developed using a T7 RNA polymerase promoter. Addition of rifampicin to inhibit the E. coli RNA polymerase after induction of the T7 RNA polymerase gene resulted in about 30% of newly synthesized protein being alpha 1-antitrypsin. This expression system was then used to examine the effect of mutations in the hinge region of alpha 1-antitrypsin on its activity. The mutations were based on ones in antithrombin III that had previously been shown to have adverse effects on activity. Mutation of Ala347 to threonine in alpha 1-antitrypsin did not affect the kinetic behavior of the protein with trypsin or human leukocyte elastase. In contrast, mutation of Gly349 to proline converted the majority of the protein into a substrate for both proteinases. The small fraction of this mutant that was active, however, had kinetic parameters that were indistinguishable from wild type alpha 1-antitrypsin. Cleavage within the reactive-site loop of wild-type alpha 1-antitrypsin causes a conformational change in the molecules (the S-to-R transition) and results in a marked increase in heat stability. This increase in heat stability was also seen upon cleavage within the reactive-site loops of both of the alpha 1-antitrypsin mutants. The results are discussed in terms of a kinetic mechanism for serpin-proteinase interactions, in which after the formation of an initial complex the serpin partitions between the formation of a stable complex and a cleavage reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347576 TI - Structure-function relations in photosystem II. Effects of temperature and chaotropic agents on the period four oscillation of flash-induced oxygen evolution. AB - The characteristic period four oscillation patterns of oxygen evolution induced by a train of single-turnover flashes were measured in dark-adapted samples as a function of temperature and upon addition of chaotropic agents. The following results were obtained: (a) Within the range of 0 < theta < 35 degrees C, the ratio of the oxygen yield induced by the 4th and 3rd flashes of the train, Y4/Y3, and the oxygen yield induced by the 2nd flash, Y2, exhibit similar dependencies on the temperature in isolated thylakoids, PS II membrane fragments, and inside out vesicles. (b) Below a characteristic temperature theta c of 20-25 degrees C, the values of Y4/Y3 and Y2, which reflect (at constant S0 dark population) the probabilities of misses and double hits, respectively, remain virtually independent of temperature, whereas above theta c these parameters increase. (c) The dark decays of S2 and S3 via fast and slow kinetics due to reduction of the water oxidase by YD and other endogenous electron donor(s), respectively, exhibit comparatively strong temperature dependencies in thylakoids with the following activation energies: EA(S2fast) = 55 kJ/mol, EA(S3fast) = 50 kJ/mol, EA(S2slow) = 85 kJ/mol, and EA(S3slow) = 75 kJ/mol. The activation energy of S0 oxidation to S1 by YDox was found to be markedly smaller with a value of EA(S0) = 30 kJ/mol. (d) Incubation with chaotropic agents at concentrations which do not significantly impair the oxygen evolution capacity leads to modifications of the oscillation pattern with remarkable differences for various types of agents: Tris and urea are practically without effect; guanidine hydrochloride affects Y4/Y3 in a similar way as elevated temperature but without significant changes of Y2 and the decay kinetics of S2 and S3; and anions of the Hofmeister series (SCN-, ClO4 , I-) cause a drastic destabilization of YDox. Possible structure-function relations of the PS II complex are discussed on the basis of these findings. PMID- 8347577 TI - Pathway of proton uptake in the bacteriorhodopsin photocycle. AB - The time courses of chromophore reactions and proton uptake in the second half of the photocycle of the proton pump bacteriorhodopsin (BR) were examined. At pH > 8.5, the kinetics are simplified by the fact that only the M and N intermediates accumulate. The relaxation kinetics after perturbation of M with a second, blue flash confirm that M<==>N equilibration is the only significant cause of the biphasic M decay. With this feature, the analysis of time-resolved difference spectra yields a scheme which contains two sequential N states connected by a nearly unidirectional reaction. The proton uptake from the bulk, as measured with the pH-indicator dye pyranine, occurs during the decay of the first N rather than the recovery of BR. The results thus suggest the model M2(-1)<==>N(-1) + H+ (from the bulk)<==>N(0)-->BR, where the superscripts indicate the protonation state of the protein relative to BR. M2(-1)-->N(-1) is reprotonation of the Schiff base from D96, N(-1) + H+ (from the bulk)-->N(0) is uptake of proton from the cytoplasmic side, and N(0)-->BR represents 13-cis to all-trans reisomerization of the retinal and other relaxations which regenerate the initial state. R227, a residue near D96, affects the deprotonation of D96 more than the subsequent proton uptake. According to the changed [M2(-1)]/[N(-1)] equilibrium in the R227Q protein, interaction between R227 and D96 is responsible for about 1 pH unit of the decrease in the pKa of D96 during the reprotonation of the Schiff base. According to the pH dependencies of the rate constants in the N(-1)<==>N(0) equilibrium in wild-type and R227Q, interaction with R227 lowers the pKa for proton uptake from the bulk by 0.5 pH unit, to 11. We conclude from the proton uptake kinetics that at physiological pH free energy is converted to proton electrochemical potential in this pump not only as protons are released on the extracellular side [Zimanyi, L., Varo. G., Chang, M., Ni, B., Needleman, R., & Lanyi, J. K. (1992) Biochemistry 31, 8535-8543] but also as protons are taken up on the cytoplasmic side. PMID- 8347578 TI - Photoreaction of the N intermediate of bacteriorhodopsin, and its relationship to the decay kinetics of the M intermediate. AB - Because the M photointermediate of recombinant T46V bacteriorhodopsin decays more rapidly and the N intermediate more slowly than in wild-type, the photoreaction of N could be examined without interference from M. We found that between pH 6 and 9 the photoproducts of N included both earlier suggested M-like intermediate and red-shifted R state. However, when the photoexcitation of N was at wavelengths below 500 nm the amount of M-like product decreased with increasing pH, and at pH 9 virtually only R was produced. In the dark, T46V contains an N like conformer, in increasing amounts with increasing pH like wild-type but in 4 5 times greater concentrations. The photoreaction of this thermally produced state is much like that of the N intermediate. It is associated with the appearance of a slowly decaying M, but we calculate that under most conditions used to follow M in the wild-type photocycle the amount of N-like conformer, and therefore the amplitude of this slow component, will not be significant. The results confirm the suggestion [Fukuda & Kouyama (1992) Biochemistry 31, 11740 11747] that an M-like state is included among the photoproducts of N, but at the same time provide support to photocycle models in which the slow component of the biphasic M decay is attributed not to this secondary photoreaction or to a separate photocycle originating from a heterogeneous initial state, but to thermal equilibration between M and N in a single photocycle. PMID- 8347579 TI - Kinetic analysis of the induction period in lipoxygenase catalysis. AB - The dioxygenation of 50 microM linoleate at 0.1 microM (13S) hydroperoxylinoleate, 240 microM O2, pH 10, and 25 degrees C, catalyzed by varying amounts of soybean lipoxygenase-1, was studied with rapid kinetic techniques. The aim was to assess the effect of transient redistributions of the Fe(II) and Fe(III) enzyme forms on the shape of the reaction progress curves. Reactions initiated with iron(II) lipoxygenase show an initial increase in rate, the "kinetic lag phase" or "induction period". The duration of this induction period varies from approximately 1 s at [lipoxygenase] > 20 nM to 5 s at [lipoxygenase] = 3 nM. At [lipoxygenase] < 2 nM, the duration of the induction period in these curves is inversely proportional to [lipoxygenase]. The integrated steady-state rate equation for the single fatty acid binding site model of lipoxygenase catalysis [Schilstra et al. (1992) Biochemistry 31, 7692 7699] also shows an induction period whose duration is inversely proportional to [lipoxygenase]. These observations, in combination with non-steady-state numerical simulations, lead to the conclusion that, at [lipoxygenase] < 2 nM, pre steady-state redistributions of enzyme intermediates occur fast with respect to the rate at which the concentrations of substrates and products change. At higher lipoxygenase concentrations, the pre-steady-state redistributions contribute significantly to the induction period. From a nonlinear least-squares fit to the steady-state rate equation of data obtained at lipoxygenase concentrations of 0.5 and 1 nM, it was calculated that 1% of the linoleate radicals that are formed after hydrogen abstraction dissociate from the active site before enzymic oxygen insertion has occurred. PMID- 8347580 TI - Kinetic and equilibrium analysis of the interactions of actomyosin subfragment 1.ADP with beryllium fluoride. AB - The hypothesis that the stable ternary complex formed between myosin subfragment 1, MgADP and beryllium fluoride (BeF3-), denoted S-1 not equal to .ADP.BeF3-, is an analog of the intermediate state S-1**.ADP.P(i) has been tested in this work by examining the interactions of S-1 not equal to .ADP.BeF3- with actin. Equilibrium binding measurements revealed that actin bound weakly to the S-1 not equal to .ADP.BeF3- complex (Ka = 10(4) M-1) in the presence of 40 mM KCl. The stability of this complex was strongly salt-dependent. The association constant of BeF3- to the acto-S-1.ADP complex (KBe approximately 10(3) M-1) was 100-fold weaker than its binding to the S-1.ADP complex. While inhibiting the S-1 ATPase strongly, BeF3- had no effect on the Vmax value (10 +/- 1.0 s-1) of the actin activated ATPase of S-1. The rates of BeF3- binding and dissociation from the acto-S-1.ADP.BeF3- complex were determined by stopped-flow measurements. The hyperbolic dependence of the rates of BeF3- binding to acto-S-1.ADP (kobs) on BeF3- concentrations suggested that the acto-S-1.ADP.BeF3- complex was formed in at least two steps: binding followed by isomerization. The binding constant was 1.2 x 10(3) M-1, and the maximum kobs was 2.5 s-1. The dissociation of BeF3- from the acto-S-1.ADP.BeF3- complex was monitored via decrease in the fluorescence of 1-N6-ethenoadenosine diphosphate (epsilon ADP). The fluorescence decrease fitted two exponential terms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347581 TI - Orientation of functional and nonfunctional PTS permease signal sequences in lipid bilayers. A polarized attenuated total reflection infrared study. AB - Synthetic peptides corresponding to the N-terminal 23 and 22 residues, respectively, of two integral plasma membrane proteins of Escherichia coli, namely the mannitol- and glucitol-specific permeases of the bacterial sugar phosphotransferase system, were incorporated into single planar phospholipid bilayers supported on germanium plates. Polarized attenuated total reflection infrared spectra were recorded, and order parameters were derived from the measured dichroic ratios. The order parameters of the two wild-type peptides which form amphiphilic alpha-helices in membranes were -0.4 to -0.5, indicating a preferential alignment of the alpha-helix long axis parallel to the membrane surface. Nonfunctional mutant peptides of the mannitol permease sequence in which serine-3 or aspartate-4 were substituted with prolines (S3P and D4P) or lysine (D4K), but which were still largely alpha-helical, exhibited peptide order parameters close to zero, indicating a high degree of disorder of these peptides in the lipid bilayers. The lipid was well ordered at low concentrations of peptides in the membranes but became disordered at high peptide concentrations. This effect of lipid disordering was more pronounced for the D4K mutant than for the wild-type mannitol peptide. PMID- 8347582 TI - Cold denaturation-induced conformational changes in phosphoglycerate kinase from yeast. AB - The temperature-dependent conformational equilibrium of 3-phosphoglycerate kinase has been studied in the temperature range from 1 to 30 degrees C by means of dynamic light scattering, small-angle X-ray scattering, differential scanning calorimetry, circular dichroism spectroscopy, and fluorescence spectroscopy. At 28 degrees C and in the presence of 0.7 M guanidine hydrochloride (GuHCl), the radius of gyration (RG) and the Stokes radius (RS) are 2.44 and 3.09 nm, respectively. Decreasing the temperature effects unfolding of the molecule, a process that involves two stages. The two stages correspond to the successive unfolding of the N-terminal and C-terminal domains. The peak maxima of the excess heat capacity, determined from differential calorimetric scans, extrapolated to 0 scan rate, are positioned at 16.5 degrees C for the N-terminal domain and at 6.3 degrees C for the C-terminal domain. At 4.5 degrees C, the radius of gyration and the Stokes radius increase to 7.8 and 4.8 nm, respectively. The persistence length and the length of the statistical chain segment of the unfolded polypeptide chain are 1.74 and 3.48 nm, corresponding to five and ten amino acids, respectively. At 1 degrees C, the dimensions of the unfolded chain nearly agree with the predicted dimensions under theta conditions. Thus, the conformational changes upon cold denaturation can be described by a transition from a compactly folded molecule to a random coil. The conformation-dependent ratio rho = RGRS-1 increases from rho = 0.79 to rho = 1.63. The volume of the unfolded chain is 30 times larger than that of the folded chain in the native state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347583 TI - Cold denaturation of yeast phosphoglycerate kinase: kinetics of changes in secondary structure and compactness on unfolding and refolding. AB - Under mildly destabilizing conditions (0.7 M GuHCl), phosphoglycerate kinase from yeast undergoes a reversible two-step equilibrium unfolding transition when the temperature is lowered from 30 to 1 degree C (Griko, Y. V., Venyaminov, S. Y., & Privalov, P. L. (1989) FEBS Lett. 244, 276-278). The kinetics of the changes in compactness and secondary structure have been studied by means of dynamic light scattering and far-UV circular dichroism, respectively. It turned out that unfolding and refolding after an appropriate temperature jump (T-jump) was performed proceeded in substantially different ways. After a T-jump from 30 to 1 degree C, a multiphasic unfolding behavior was observed, reflecting the independent unfolding of the N-terminal and C-terminal domains with time constants of about 7 and 45 min, respectively. A remarkable feature of the unfolding process is the simultaneous change of compactness and secondary structure. Refolding after a T-jump from 1 degree C to higher temperatures occurs in two stages. At the first stage an appreciable amount of secondary structure is formed rapidly within the dead time of the T-jump, while the overall dimensions of the polypeptide chain remain essentially unchanged. Thus, an extended folding intermediate is formed at an early stage of folding. Further information of secondary structure proceeds slowly within a time range of minutes in parallel with the increase of compactness. At 30 degrees C, both domains refold simultaneously, while at 15 degrees C, independent folding can be observed. These findings are discussed with respect to predictions of existing models of folding. PMID- 8347584 TI - Fluorescence anisotropy assays implicate protein-protein interactions in regulating trp repressor DNA binding. AB - The study of interactions between proteins and nucleic acids is central to the understanding of the control of genetic expression. Fluorescence anisotropy has been used to measure, in solution, the equilibrium binding profiles of a bacterial repressor protein, the tryptophan repressor (TR), to a fluorescently labeled oligonucleotide containing one of its target operator sequences. Investigation of the effects of changing concentrations of corepressor, operator DNA, and protein implicate TR oligomers in the regulation of DNA binding. These studies also demonstrate that the relatively straightforward technique of fluorescence anisotropy can be applied to the study of the interactions between proteins and nucleic acids. The fluorescence technique exhibits sufficient sensitivity to replace radioactive methods of detection in most cases. In addition, since it is a solution-based methodology, it offers a true equilibrium measure of the protein-nucleic acid equilibria, and the effects of changes in solution conditions such as salt and ligand concentration, pH, and temperature can be readily evaluated. Data acquisition is relatively simple and rapid, and the data are of sufficient quality for detailed thermodynamic analyses of complex systems. Given these attributes, fluorescence anisotropy will find multiple applications in the area of genetic regulation. PMID- 8347585 TI - Thermal stability of the DNA-binding domain of the Myb oncoprotein. AB - The DNA-binding domain of the c-myb protooncogene product consists of three homologous tandem repeats of 51-52 amino acids (denoted as R1, R2, and R3 from the N-terminal side). In order to analyze conformational and thermodynamic characteristics of the homologous repeats, we have examined the DNA-binding domain by circular dichroism (CD) and differential scanning calorimetry (DSC). The CD spectra for the three individual repeats are significantly different in the fine profiles, indicating subtle differences in their conformations. The melting analyses for the fragments show that the thermal stability of each fragment is different from one another, with the following order of stability: R1(Tm = 61 degrees C) approximately greater than R3(57 degrees C) >> R2(43 degrees C), where R2 is much less stable than the other repeats. The denaturing process for the whole DNA-binding domain, measured by DSC, is characterized by a very broad transition ranging from 30 to 80 degrees C. The denaturation curve can be fit well by a three-state transition with one intermediate state. The transition temperature for the native-to-intermediate transition coincides with the melting temperature of R2, indicating that the intermediate state corresponds to the unfolding of unstable R2. The CD spectrum of the whole domain is almost identical to the sum of the individual spectra. Thus, these results suggest that the individual repeats in the whole DNA-binding domain behave independently in terms of conformation and stability. The addition of DNA to the DNA-binding fragment drastically changed the melting profile, in which the broad transition curve was replaced by a sharp peak at 58 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347587 TI - Specific glycosylation site mutations of the insulin receptor alpha subunit impair intracellular transport. AB - The insulin receptor is a transmembrane protein found on multiple cell types. This receptor is synthesized as a 190-kDa proreceptor which is cleaved to produce mature alpha and beta subunits. The proreceptor contains 18 potential sites for N linked glycosylation: 14 on the alpha subunit and 4 on the beta subunit. The codons for asparagine in the first four sites at the amino terminus of the alpha subunit were mutated to code for glutamine. This mutant receptor cDNA was stably transfected into NIH 3T3 cells. The insulin receptor produced in these cells remained in the proreceptor form; no mature alpha and beta subunits were produced. The proreceptor was slightly smaller on SDS-PAGE gels than the wild type proreceptor and contained four less oligosaccharide chains by tryptic peptide mapping. The carbohydrate chains on the mutant proreceptor remained endoglycosidase H sensitive. However, in the presence of brefeldin A, these oligosaccharide chains could be processed to endoglycosidase H resistant chains. By immunofluorescence, the mutant proreceptor was shown to be localized to the endoplasmic reticulum. No insulin receptors could be found on the cell-surface either with cell surface labeling with biotin or with 125I-insulin binding. Thus, glycosylation of the first four N-linked glycosylation sites of the insulin receptor is necessary for the proper processing and intracellular transport of the receptor. This is in contrast to glycosylation at the four sites on the beta subunit which appear not to be important for processing but necessary for signal transduction. Therefore, N-linked glycosylation of the insulin receptor at specific sites has multiple distinctive roles. PMID- 8347586 TI - A new function of S-adenosylmethionine: the ribosyl moiety of AdoMet is the precursor of the cyclopentenediol moiety of the tRNA wobble base queuine. AB - Queuosine (Q) [7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deaz agu anosine] usually occurs in the first position of the anticodon of tRNAs specifying the amino acids asparagine, aspartate, histidine, and tyrosine. The hypermodified nucleoside is found in eubacteria and eucaryotes. Q is synthesized de novo exclusively in eubacteria; for eucaryotes the compound is a nutrient factor. In Escherichia coli the Q precursor (oQ), carrying a 2,3-epoxy-4,5 dihydroxycyclopentane ring, is formed from tRNA precursors containing 7 (aminomethyl)-7-deazaguanine (preQ1) by the queA gene product. A genomic queA mutant accumulating preQ1 tRNA was constructed. The QueA enzyme was overexpressed as a fusion protein with the glutathione S-transferase from Schistosoma japonicum and purified to homogeneity by affinity and anion-exchange chromatography. The enzyme QueA synthesizes oQ from preQ1 in a single S-adenosylmethionine- (AdoMet-) requiring step, indicating that the ribosyl moiety of AdoMet is transferred and isomerized to the epoxycyclopentane residue of oQ. The identity of oQ was verified by HPLC and directly combined HPLC/mass spectrometry. The formation of oQ was reconstituted in vitro, applying a synthetic RNA. A 17-nucleotide microhelix (corresponding to the anticodon stem and loop of tRNA(Tyr) from E. coli) is sufficient to act as the RNA substrate for oQ synthesis. We propose that QueA is an S-adenosylmethionine:tRNA ribosyltransferase-isomerase. PMID- 8347588 TI - Lifetime of the histone octamer studied by continuous-flow quasielastic light scattering: test of a model for nucleosome transcription. AB - An instrument for continuous-flow quasielastic light scattering is described that allows the translational diffusion coefficient of macromolecules to be determined as a function of time after the initiation of some time-dependent process by mixing. Control experiments are carried out using the proteins lysozyme and BSA to verify that flow of the solution does not lead to erroneous results. The instrument is used to determine the lifetime of the histone octamer. A solution of octamer that is artificially stabilized in 2.0 M NaCl is rapidly diluted to physiological ionic strength, and the Stokes diameter is determined as a function of the time, delta t, after mixing. We find that the octamers dissociate into their component H2A-H2B heterodimers and H(3)2H4 tetramers on a time scale that is faster than the earliest time point for which data were obtained, 1 s after mixing. This result argues against a simple mechanism for the progression of RNA or DNA polymerase through chromatin. PMID- 8347589 TI - Forward electron transfer from phylloquinone A1 to iron-sulfur centers in spinach photosystem I. AB - Forward electron transfer at room temperature from the secondary acceptor A1 (phylloquinone) to the iron-sulfur centers FX, FB, and FA was studied by flash absorbance spectroscopy in different photosystem I (PSI) preparations in order to resolve the controversy concerning the kinetics of A1-reoxidation during forward electron transfer [half times of 15 ns [Mathis, P., & Setif, P. (1988) FEBS Lett. 237, 65-68] and 200 ns [Brettel, K. (1988) FEBS Lett. 239, 93-98] were reported for PSI particles from spinach and Synechococcus sp., respectively]. The monophasic kinetics with t1/2 approximately 200 ns could be reproduced with PSI particles from another cyanobacterium (Synechocystis sp. PCC 6803). In so-called PSI-beta particles from spinach, containing all membrane-bound electron carriers and approximately 65 antenna chlorophylls per reaction center, the flash-induced absorbance increase around 370 nm, which is indicative of the formation of A1-, decays biphasically with t1/2 approximately 25 and 150 ns and relative amplitudes of approximately 65 and 35%, respectively. The difference spectra of these two phases were determined between 330 and 500 nm; they agree well below 380 nm but deviate significantly at higher wavelengths. The spectrum of the sum of the two phases is similar to the spectrum of the 200-ns phase in cyanobacteria. Upon chemical reduction of the terminal acceptors FA and FB, only the 25-ns phase is conserved and the absorbance changes remaining after its completion decay with t1/2 approximately 250 microseconds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347590 TI - Interaction and influence of phenylalanine-198 and threonine-199 on catalysis by human carbonic anhydrase III. AB - Site-directed mutants of human carbonic anhydrase III were used to examine the role of Thr-199 and its interaction with Phe-198 in the catalyzed hydration of CO2. Threonine-199 is a hydrogen bond acceptor for the zinc-bound water, and Phe 198 forms part of the hydrophobic side of the active-site cavity of carbonic anhydrase III. Catalytic activity for a total of five single and double mutants at residues 198 and 199 was determined by stopped-flow spectrophotometry and 18O exchange between CO2 and water measured by mass spectrometry. The replacement Thr 199-->Ala resulted in a 4-fold decrease in the kcat/Km for hydration of CO2. We tested the hypothesis that the 25-fold increase in the kcat/Km for hydration of CO2 accompanying the replacement Phe-198-->Leu in isozyme III is caused by changes in the interaction of Thr-199 with the zinc-bound water or the transition state for catalysis. Comparison of hydration of CO2 by the single and double mutants of isozyme III containing the replacements Thr-199-->Ala and Phe-198- >Leu was consistent with an interaction between these two sites. PMID- 8347591 TI - Mutational effects on the cooperativity of Ca2+ binding in calmodulin. AB - The importance of the aspartate ligand in the +Y Ca2+ coordinating position of two EF-hands of calmodulin has been investigated. Synthetic calmodulin genes were used to produce engineered proteins with the wild-type bovine sequence as well as with aspartate 58 in Ca(2+)-binding site II and/or aspartate 95 in site III changed to asparagine. The macroscopic Ca(2+)-binding constants of the intact calmodulins and of tryptic fragments comprising the N- and C-terminal domains were determined from titrations with Ca2+ in the presence of 5,5'-Br2BAPTA. Substitution of aspartate by asparagine in Ca(2+)-binding site II led to a slight increase in the total free energy change on Ca2+ binding, and the cooperativity of Ca2+ binding to the N-terminal sites was substantially increased. The change from aspartate to asparagine in site III decreased the Ca2+ affinity and also appeared to decrease the positive cooperativity between the sites in the C terminal domain. Thus, identical mutations in sites II and III were found to result in opposite effects. The data imply that involvement of liganding side chains in interactions other than direct calcium attraction and calcium coordination is of considerable importance for the Ca(2+)-binding process, particularly for the cooperativity. PMID- 8347592 TI - Physical properties of apolipoprotein A-I from the chicken, Gallus domesticus. AB - The amphipathic alpha-helices of exchangeable apolipoproteins (apo) function to simultaneously facilitate interaction with lipid surfaces and the aqueous environment. In contrast to mammalian apoA-I's, which self-associate in the absence of lipid, chicken apoA-I, which shares 66% sequence homology with human apoA-I, exists as a monomeric protein when dissociated from high-density lipoprotein (HDL). Sedimentation equilibrium studies conducted in the analytical ultracentrifuge yielded a weight-average molecular weight of 28,170. Corresponding sedimentation velocity and diffusion experiments gave rise to s0(20,w) = 2.23 S and D0(20,w) = 6.39 x 10(-7) cm2/s. A translational frictional ratio (f/fmin) of 1.18 and an axial ratio of 4.0 were also determined from this data. The Stokes radius (Rs,sed = 2.80 nm) and translational frictional ratio were subsequently used to calculate estimated molecular dimensions of 25.2 x 100.8 A for chicken apoA-I. Circular dichroism (CD) studies revealed a highly alpha-helical structure predicted to be 74% by Provencher-Glockner analysis. Denaturation studies performed on lipid-free apoA-I and monitored by CD revealed a midpoint of denaturation of 0.64 M guanidine hydrochloride. From plots of delta G(app) versus guanidine hydrochloride concentration, a delta GDH2O of 1.86 kcal/mol was determined. In other studies, a midpoint of temperature-induced denaturation for apoA-I of 57 degrees C was obtained. The effect of solvent pH on the secondary structure content of apoA-I revealed a significant loss of alpha helix below pH 4.0 and above pH 10, suggesting that lipid-free apoA-I may by partially stabilized by the formation of intra- or interhelix salt bridges between oppositely charged amino acid side chains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347593 TI - Membrane interaction and self-assembly within phospholipid membranes of synthetic segments corresponding to the H-5 region of the shaker K+ channel. AB - The voltage-activated K+ channels are assumed to be formed by the coassembly of four polypeptide monomers. Each of these monomers is postulated to consist of six transmembrane segments (S1 to S6), and long N- and C-terminal domains. The highly conserved linker, H-5, between the fifth and the sixth transmembrane segments, is hypothesized to line the lumen of the K+ channel formed by the bundle of the transmembrane segments of the monomers. Herein we utilize the spectrofluorometric approach and investigate the interaction with phospholipid membranes of fluorescently-labeled synthetic peptides, whose sequences are derived from the H 5 region. Binding experiments reveal that the peptides can strongly bind to phospholipid membranes with partition coefficients on the order of 10(4) M-1. However, a truncated peptide without four amino acids within the most conserved region (amino acids 432-435) did not bind to the membranes at all. Moreover, the single substitution of a conserved tryptophan at position 435 to serine reduced the partition coefficient of the peptide approximately 5-fold, which may account for a mutated K+ channel with this substitution not producing functional channels (Yool & Schwarz, 1991). Structural characterization using circular dichroism spectroscopy (CD) reveals that H-5 can partially adopt an alpha-helix structure in hydrophobic environments. Resonance energy transfer (RET) experiments reveal that the H-5-derived segments can self-assemble within the membrane but cannot coassemble with other unrelated membrane-bound peptides. The results herein support the hypothesis that H-5 segments are packed in close proximity and might participate in mediating the appropriate assembly of the core region of K+ channel monomers. PMID- 8347594 TI - Cholesterol interacts with lactosyl and maltosyl cerebrosides but not with glucosyl or galactosyl cerebrosides in mixed monolayers. AB - Pure and mixed monolayers of mono- and dihexoside cerebrosides with cholesterol have been characterized at the air/water interface. Cholesterol oxidase was used as a reporter enzyme for the cholesterol-cerebroside interaction in the mixed monolayers. The cerebrosides either were derived from bovine brain extracts or were synthetic. The dihexoside cerebrosides were synthesized by coupling of the hepta-O-acetyl-alpha-lactosyl- or maltosylphosphoramidates with D-erythro-N acylceramides in dichloromethane, in the presence of trimethylsilyl triflate and molecular sieves, followed by hydrolysis of the acetate-protecting groups. All of the bovine-brain-derived cerebrosides [galactosyl cerebroside (GalCer, types I and II), glucosyl cerebroside (GlcCer), and lactosyl cerebroside (LacCer)] had very condensed force-area isotherms (compressibility values of 3-5 x 10(-3) m/mN at 20 mN/m), as did the synthetic N-stearoylmaltosylceramide (N-18:0 MaltCer). Shorter-chain synthetic cerebrosides (N-8:0 LacCer and N-8:0 MaltCer) had more expanded isotherms, with compressibility values of 15-17 x 10(-3) m/mN. When cholesterol was included in mixed monolayers of monohexoside cerebroside, it did not induce significant condensation of packing (indicating that cholesterol did not increase the order of the acyl chains). However, with dihexoside cerebrosides, a cholesterol-induced condensing effect was observed, which amounted to a 11-19% reduction in the observed mean molecular area. When cholesterol oxidase was used to titrate the stoichiometry of cholesterol/cerebroside in mixed monolayers, at which pure cholesterol clusters appeared, it was observed that in monohexoside cerebroside monolayers cholesterol clusters were present even below a 1:1 molar stoichiometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347595 TI - Activation of UDP-galactose:globotriaosylceramide alpha 1-3-galactosyltransferase during PC12D cell differentiation induced by galactosylceramide. AB - We measured the activities of UDP-galactose:globotriaosylceramide alpha 1-3 galactosyltransferase (alpha-GalTase) and protein kinase C (PKC) in PC12D pheochromocytoma (PC12D) cells which were induced to differentiation by nerve growth factor (NGF), forskolin (FRK), staurosporine (STP), retinoic acid (RA), 2 chloroadenosine (ClAd), and/or galactosylceramide (GalCer). NGF, STP, FRK, and RA were found to be stimulators for the PKC activity, whereas ClAd appeared to be an inhibitor of the enzyme. At the concentration of 25 microM, GalCer having normal fatty acids was found to be a stimulator, whereas GalCer having hydroxy fatty acids was ineffective in modulating the PKC activity. Interestingly, all stimulators of PKC activities, including GalCer having normal fatty acids, appeared to be activators for the alpha-GalTase activity. On the other hand, GalCer having alpha-hydroxy fatty acids had no effect and ClAd was found to be a potent inhibitor for the alpha-GalTase activity. These data suggest that alpha GalTase activity during PC12D cell differentiation may be regulated by a PKC dependent process. PMID- 8347596 TI - Affinity purification and binding analysis of the hemolymph juvenile hormone binding protein from Manduca sexta. AB - A high-affinity juvenile hormone binding protein was purified from the hemolymph of the tobacco hornworm, Manduca sexta, employing ammonium sulfate precipitation and affinity and size-separation chromatography. The naturally occurring enantiomer of juvenile hormone III (10R) was converted to juvenile hormone III acid and then covalently attached to aminohexyl-Sepharose 4B. Hemolymph from early fifth stadium (60 h postecdysis) larvae was used as the source of hJHBP. The yield of hJHBP was approximately 25% of the starting material, with 3.5 mg of highly purified, biologically active hJHBP recovered from 100 mL of hemolymph. Binding parameters were examined using equilibrium dialysis and highly purified, enantiomerically correct juvenile hormone I and II and racemic JH III. The equilibrium dissociation constants for juvenile hormone I and II were approximately 6 x 10(-10) M at 4 degrees C, while racemic juvenile hormone III displayed an equilibrium dissociation constant of 1.9 x 10(-9) M. At 25 degrees C the equilibrium dissociation constant for juvenile hormone I was 1.6 x 10(-9) M. Half-times of dissociation were also determined for the three homologs. The half time of dissociation was 30 s for juvenile hormone I, 20 s for juvenile hormone II, and 13 s for juvenile hormone III at either 4 or 25 degrees C. Using the new equilibrium dissociation constants, we calculate that better than 99% of the circulating juvenile hormone titer may be bound to this hemolymph protein. PMID- 8347597 TI - Expression and characterization of biologically active human hepatocyte growth factor (HGF) by insect cells infected with HGF-recombinant baculovirus. AB - A cDNA containing the entire coding sequence of human hepatocyte growth factor (HGF) [also known as scatter factor (SF)] was inserted into the genome of Autographa california nuclear polyhedrosis virus (baculovirus) adjacent to the polyhedrin promoter by homologous recombination. Insect cells (Spodoptera frugiperda) infected with the recombinant virus secrete relatively high levels (3 8 mg/L) of biologically active HGF into the culture medium. The recombinant HGF induces pronounced morphological changes and scattering of primary cultures of rat, mouse, and human hepatocytes within 24 h after plating and stimulates DNA synthesis in these cells with the same magnitude as native HGF derived from human placenta or rabbit serum. The human recombinant HGF produced by the insect cells is N-glycosylated, binds to heparin like native HGF, and is recognized by polyclonal antiserums raised against human or rabbit HGF as assessed by immunoblot, ELISA, and immunoneutralization experiments. Metabolic radiolabeling with L-[35S]methionine (pulse-chase experiments) as well as Western blot analysis indicates that the recombinant HGF is synthesized and secreted by the infected insect cells as the unprocessed single-chain form (pro-HGF) when the cells are cultured in serum-free medium. However, when the infected insect cells are cultured in insect culture medium (Grace's medium) containing fetal bovine serum, the secreted HGF is present mainly in the mature heterodimeric form. Addition of serum to the baculovirus-expressed single-chain [125I]HGF in a cell-free system results in conversion to the heterodimeric two-chain form, and the activation is prevented by the serine protease inhibitor PMSF. Incubation of 125I-labeled pro HGF with rat liver or spleen extracts resulted in conversion of pro-HGF to the heterodimeric two-chain form. A truncated form of HGF containing the N-terminal portion of HGF (kringles 1-3) was also produced in the same expression system. This deleted HGF, by itself, did not have any detectable biological activity; however, it abrogated the stimulatory effects of full-length HGF on hepatocytes. This is the first successful production of bioactive recombinant HGF in large quantities, which will allow purification on the milligram scale of pro-HGF and will permit future studies to elucidate pathways involved in HGF activation by its target tissues. PMID- 8347598 TI - Structural organization and chromosomal assignment of the gene encoding the human heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor. AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently identified, potent smooth muscle cell mitogen of macrophage origin. It is expressed in a highly regulated fashion in vascular endothelial and smooth muscle cells, indicating a potentially important role for this gene in atherosclerosis. In addition, the HB-EGF precursor has recently been found to function as a receptor for diphtheria toxin. Using an HB-EGF cDNA probe, we cloned the human gene encoding HB-EGF. The HB-EGF gene contains six exons and five intervening sequences spanning 14 kb of DNA. By primer extension and S1 nuclease analysis, we located a major transcription start site (corresponding to an A residue) 14 bp beyond the 5' end of the HB-EGF cDNA. There were no TATAAA or CCAAT consensus sequences upstream of the transcription start site. The density of primer extension bands generated by RNA from endothelial cells treated with tumor necrosis factor-alpha (TNF-alpha) was 10 times higher than that of bands generated by the control, indicating that TNF-alpha increased the level of HB-EGF mRNA. Using transient reporter gene transfection experiments, we show that 2.0 kb of HB-EGF 5'-flanking sequence has promoter activity in bovine aortic endothelial cells. By analysis of DNA isolated from human-mouse somatic hybrid cell lines, we assign the HB-EGF gene to chromosome 5. By functional study, chromosome 5 has been associated with diphtheria toxin susceptibility. PMID- 8347599 TI - In vitro protein engineering using synthetic tRNA(Ala) with different anticodons. AB - The use of synthetic tRNA for in vitro protein engineering was tested in a coupled transcription/translation system prepared from Escherichia coli. DNA sequences similar to the natural tRNA(Ala/UGC) gene from E. coli but with different anticodons were synthesized in vitro, cloned into a DNA plasmid, and then transcribed in vitro with T7 RNA polymerase. The UGC alanine anticodon was changed to CUA corresponding to the UAG stop codon, CCU corresponding to the rarely used AGG arginine codon, and two four-nucleotide anticodons used to suppress stop codons. Bacterial dihydrofolate reductase was the test protein. Its cloned coding sequence was mutagenized at the GUG codon for valine-75 to correspond to the anticodons of the tRNA constructs, and then the plasmids were used to direct the synthesis of dihydrofolate reductase in the coupled transcription/translation system containing the corresponding synthetic tRNA. The results indicate that all four synthetic tRNAs were functionally active in the synthesis of full-length, enzymatically active dihydrofolate reductase protein. PMID- 8347600 TI - Self-splicing of the group I intron from Anabaena pre-tRNA: requirement for base pairing of the exons in the anticodon stem. AB - In the cyanobacterium Anabaena, the precursor to tRNA(Leu) has a 249-nucleotide group I intron inserted between the wobble and second bases of the anticodon; the intron self-splices during transcription in vitro [Xu, M. Q., Kathe, S. D., Goodrich-Blair, H., Nierzwicki-Bauer, S. A., & Shub, D. A. (1990) Science 250, 1566-1570]. By studying splicing of isolated pre-tRNA, we confirm that splicing occurs by the two-step transesterification mechanism characteristic of group I introns, resulting in excision of the intron and accurate ligation of the 5' and 3' exons. The first step, guanosine-dependent cleavage of the phosphodiester bond at the 5' splice site, occurs with kcat congruent to 14 min-1 and kcat/Km = 5 x 10(4) M-1 min-1 (32 degrees C, 15 mM MgCl2), unexpectedly efficient for a small group I intron. (kcat/Km is comparable to that of the Tetrahymena pre-rRNA intron, and kcat is an order of magnitude higher than any previously reported for a group I intron). The second step, ligation of the exons, is so slow (k = 0.3 min-1) that it is rate-limiting for splicing in vitro except at very low guanosine concentrations. Disruption of the base pairs that make up the anticodon stem of the tRNA dramatically reduces the rate of the first step of splicing, while compensatory mutations that restore base pairing generally restore activity. We suggest that the very short P1 helix of this pre-tRNA, with only three base pairs preceding the 5' splice site, is unstable without the additional base pairs in the anticodon stem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347601 TI - Inhibition of human immunodeficiency virus-1 protease by a C2-symmetric phosphinate. Synthesis and crystallographic analysis. AB - The human immunodeficiency virus type 1 (HIV-1) protease is a potential target of acquired immune deficiency syndrome (AIDS) therapy. A highly potent, perfectly symmetrical phosphinate inhibitor of this enzyme, SB204144, has been synthesized. It is a competitive inhibitor of HIV-1 protease, with an apparent inhibition constant of 2.8 nM at pH 6.0. The three-dimensional structure of SB204144 bound to the enzyme has been determined at 2.3-A resolution by X-ray diffraction techniques and refined to a crystallographic discrepancy factor, R (= sigma parallel F(o) magnitude to - Fc parallel/sigma magnitude of F(o)), of 0.178. The inhibitor is held in the enzyme active site by a set of hydrophobic and hydrophilic interactions, including an interaction between Arg8 and the center of the terminal benzene rings of the inhibitor. The phosphinate establishes a novel interaction with the two catalytic aspartates; each oxygen of the central phosphinic acid moiety interacts with a single oxygen of one aspartic acid, establishing a very short (2.2-2.4 A) oxygen-oxygen contact. As with the structures of penicillopepsin bound to phosphinate and phosphonate inhibitors [Fraser, M. E., Strynadka, N. C., Bartlett, P. A., Hanson, J. E., & James, M. N. (1992) Biochemistry 31, 5201-14], we interpret this short distance and the stereochemical environment of each pair of oxygens in terms of a hydrogen bond that has a symmetric single-well potential energy curve with the proton located midway between the two atoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347602 TI - Time-resolved energy transfer measurements of donor-acceptor distance distributions and intramolecular flexibility of a CCHH zinc finger peptide. AB - Time-resolved frequency-domain fluorescence energy transfer measurements have been used to investigate the solution structure of a single-domain CCHH-type zinc finger peptide. These measurements reveal not only the range of accessible distances for a given donor-acceptor pair within the molecule but also the degree of conformational flexibility that occurs in solution. Two donor-acceptor (D-A) pair zinc finger peptides have been synthesized. A single tryptophan residue located at the midpoint of the sequence was the energy donor for two different acceptors. One acceptor, attached at the amino terminus was a 5-(dimethylamino)-1 naphthalenesulfonyl (DNS) group; the second acceptor was a 7-amino-4-methyl coumarin-3-acetyl (AMCA) group, attached to the epsilon-amino function of a carboxy-terminal lysine residue. Distance distributions and the mutual site-to site diffusion coefficients were determined for these two D-A-labeled peptides under zinc-bound, metal-free, and denatured conditions. The D-A distance distributions determined for these two peptides under metal-free and zinc-bound conditions indicated a shorter distance and a unique conformation (narrow distribution) when metal was bound and a longer distance with greater conformational flexibility when metal ion was absent. No site-to-site diffusion was detected for the zinc-bound peptide, whereas an appreciable amount of diffusion was measured for both metal-free and denatured peptide. Anisotropy measurements on the peptides indicated increased flexibility of all regions of the peptide chain in the absence of zinc and a more compact, less flexible structure when zinc was bound. It was concluded from these results that the metal bound conformation represents a unique, well-defined structure. Comparison of distance distributions measured for metal-free and denatured peptide indicated that there is some residual structure present in the metal-free peptide. PMID- 8347603 TI - Stabilization of a protein by guanidinium chloride. AB - Guanidinium chloride is a commonly used denaturant to unfold native proteins and to determine their Gibbs free energy of stabilization, delta Gstab. Here we show that this denaturant has a dual role for the stability and the folding of the model protein ribonuclease T1. When present at low concentration (0-0.3 M), guanidinium chloride stabilizes the folded protein toward thermal and urea induced unfolding and decreases the rate of unfolding. At high concentration the function of guanidinium chloride as a denaturant dominates and ribonuclease T1 is cooperatively unfolded. Ribonuclease T1 is also strongly stabilized by other salts, such as NaCl, at low concentrations, and the dependence of the thermal stability on salt concentration is not linear. Such a complex behavior was not found in control experiments with pancreatic ribonuclease A. The stabilization in the presence of low concentrations of guanidinium chloride originates probably from the binding of guanidinium ions to one or a few cation binding sites that exist in native ribonuclease T1. It is not observed when an additional salt, NaCl, is present simultaneously. The favorable interaction of guanidinium chloride with the native protein leads to increased values for delta Gstab, when unfolding transitions induced by guanidinium chloride are analyzed on the basis of the two-state model by the linear extrapolation procedure. The noncoincidence of these delta Gstab values with stability data derived from urea-induced or thermal unfolding transitions does not imply that the two-state model is not appropriate but that the linear extrapolation to zero molar denaturant is incorrect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347604 TI - Mobility at the TpA cleavage site in the T3A3-containing AhaIII and PmeI restriction sequences. AB - Lefevre et al. originally observed conformational transitions at the TpA step in the TTAA Pribnow box sequence of the trp promoter [Lefevre, J.-F., Lane, A. N., & Jardetzky, O. (1985) FEBS Lett. 190, 37-40]. In 500-MHz 1H NMR studies on the TnA(n)-containing DNA oligonucleotides [d(CGAGGTTTAAACCTCG)]2, [d(GCTCCTTTAAAGGAGC)]2, and [d(GCCGTTAACGGC)]2, we observe that, in addition to the H2 proton (which resides in the minor groove of DNA), the H8 proton of the first adenine (which resides in the major groove) is also broadened due to motion at the TpA junction. In analogous 16-mers where the T3A3 segment has been replaced by an A3T3 sequence, and therefore contains CA, GA, and AT steps (but no TA steps), all adenine proton resonances are narrow, indicating that the broadening occurs only at TpA steps. Assuming chemical exchange in the form of conformational dynamics, e.g., oscillation of the purine base about the glycosidic torsion angle, the experimental 500-MHz 1H T1 rho and 2D-NOESY data were used to constrain the correlation time of the internal motion to a range between the T1 and T1 rho minima. Calculated line shapes using a two-site exchange model indicate that the motion has an amplitude of 20-50 degrees with an associated tau c of ca. 1.6 x 10(-4) to 1.0 x 10(-5) s rad-1, respectively. The mobility appears to be a consequence of the structure at the TpA junction which is characterized by (1) a wide minor groove between two regions of narrow minor groove, (2) an unusual average orientation of the adenine heterocycle probably resulting from a poor base-stacking interaction of the adenine with the preceding thymine, and (3) a sharp discontinuity in the sugar conformation at the TpA step. PMID- 8347605 TI - Solution structure of cardiotoxin V from Naja naja atra. AB - Cardiotoxins are small proteins that are found in the venoms of snakes from the Elapidae family. These toxins are known to bind to and disrupt the organization, integrity, and function of the cell membrane. Most of the well-studied cardiotoxins cause depolarization of membrane potentials and/or lysis of red cells. In contrast, CTX V from Naja naja atra displays poor hemolytic activity but is proficient at inducing aggregation and fusion of sphingomyelin vesicles [Chien et al. (1991) J. Biol. Chem. 266, 3252-3259]. To determine whether the unique activity of this CTX is attributable to its tertiary structure, the solution structure of CTX V was determined by NMR methods. On the basis of these studies, this cardiotoxin has the same general topology as other members of the family, and thus its unusual properties do not arise from any gross structural differences that are detectable by solution NMR methods. Molecular dynamics calculations indicate that residues 36-50 show concerted fluctuations. On the basis of sequence similarity, we postulate that residues 30-34 are important in determining the specificity of cardiotoxins for fusion versus lysis of vesicles. PMID- 8347606 TI - Electrostatic calculations of side-chain pK(a) values in myoglobin and comparison with NMR data for histidines. AB - Site-specific titration curves for 12 histidine residues in carbon monoxy sperm whale myoglobin (MbCO) have been determined from two-dimensional (2D) double quantum NMR experiments. Eight of these histidine residues are observed to titrate over the accessible pH range, and pK(a) values have been determined; bounds on the titration midpoints of the remaining four histidines are also reported. Results for residues 48, 81, and 119 differ significantly from those estimated from earlier, one-dimensional studies, but they are in good agreement with values recently determined for metaquomyoglobin. These experimental values (plus those determined earlier for tyrosine titrations) are compared to predictions from crystal structures of myoglobin using a numerical Poisson Boltzmann model and a Monte Carlo treatment of the multiple-site titration. An extension of existing models is described that accounts for alternate tautomers for histidines. Calculations are reported using several choices for radii and charges, and for five crystal structures, in order to assess the sensitivity of the results to details of the calculations. In general, the agreement between calculated and observed titration behavior suggests that this theoretical model captures much of the electrostatic behavior in this system, even though it ignores conformational fluctuations and the differences in mean structures that may exist between crystal and solution. Interactions among titrating groups are often important; in general, these interactions lead to more gradual individual site titrations (the mean Hill coefficient is about 0.8), and in several cases the interactions are so strong that two side chains need to be considered as a unit and single residues may participate in two-step titrations. It is suggested that histidines involved in such two-step titrations and carboxylic acid residues with abnormally low pK(a) values in the native conformation may be involved in the acid-induced partial unfolding of MbCO. PMID- 8347607 TI - The G protein alpha s subunit incorporates [3H]palmitic acid and mutation of cysteine-3 prevents this modification. AB - We investigated whether alpha s could be acylated by palmitate by transfecting COS cells with the cDNA for the wild-type, long form of alpha s and metabolically labeling with [3H]palmitate or [35S]methionine. Cells were separated into particulate and soluble fractions and immunoprecipitated with a specific peptide antibody. [3H]Palmitate was incorporated into both endogenous and transfected alpha s. Inhibition of protein synthesis with cycloheximide did not block the radiolabeling of alpha s with [3H]palmitate. Hydroxylamine treatment caused a release of the tritium radiolabel, demonstrating that the incorporation was through a thioester bond. The tritium radiolabel was base-labile and comigrated with [3H]palmitate on thin-layer chromatography. The third residue of the wild type alpha s was mutated from a cysteine to an alanine by site-directed mutagenesis. This mutant was expressed in COS cells and localized to the particulate fraction as determined by immunoprecipitation of the [35S]methionine labeled cells. The cysteine-3 mutant did not undergo radiolabeling with [3H]palmitate, indicating that this residue is crucial for the modification. PMID- 8347608 TI - Structure of the altromycin B (N7-guanine)-DNA adduct. A proposed prototypic DNA adduct structure for the pluramycin antitumor antibiotics. AB - Altromycin B belongs to the pluramycin family of antitumor antibiotics, which also includes kidamycin, hedamycin, pluramycin, neopluramycin, DC92-B, and rubiflavin A. These potent antitumor compounds react with DNA in as yet imprecisely determined ways. In the present investigation, we have used gel electrophoresis methods in combination with nuclear magnetic resonance and mass spectrometry to determine the structure of the altromycin B-DNA adduct. High resolution gel electrophoresis demonstrated that guanine was the reactive base, and N7 was implicated from experiments in which N7-deazaguanine was used in place of guanine in a strand breakage assay. Experiments using supercoiled DNA demonstrated that altromycin B and related drugs intercalated into DNA, which implicated this as a common mechanism for binding of the pluramycin antibiotics to DNA. The altromycin B-guanine adduct was isolated from calf thymus DNA after thermal depurination of the alkylated DNA. Mass spectrometry confirmed that altromycin alkylated DNA through guanine, and 1H- and 13C-NMR was used to confirm the covalent linkage sites between altromycin B and guanine. On the basis of these results, we propose that altromycin B first intercalates into DNA via a threading mechanism, reminiscent of nogalamycin, to insert the disaccharide into the minor groove and position the epoxide in the major groove in proximity to N7 of guanine. Nucleophilic attack from N7 of guanine leads to an acid-catalyzed opening of the epoxide, resulting in the altromycin B-DNA adduct. On the basis of these results, a general mechanism for the interaction of the pluramycin family of antibiotics with DNA is proposed. PMID- 8347609 TI - Structure of the complex between pyridoxal 5'-phosphate and the tyrosine 225 to phenylalanine mutant of Escherichia coli aspartate aminotransferase determined by isotope-edited classical Raman difference spectroscopy. AB - The azomethine (Schiff base) linkage between the epsilon-amino group of active site lysine 258 and the carbonyl moiety of enzyme-bound pyridoxal 5'-phosphate (PLP) normally exhibits absorbance maxima at ca. 360 (high-pH form) or ca. 430 nm (low-pH form). However, the absorbance maximum is shifted from 358 to 386 nm, a value which is similar to that of free PLP (lambda max = 388 nm), in a mutant form of Escherichia coli aspartate aminotransferase (AATase) in which tyrosine 225, which normally donates a hydrogen bond to the phenolate function of PLP, has been replaced with phenylalanine (Y225F). This spectral shift suggested that PLP binds to Y225F as the free aldehyde. The following evidence from isotope-edited classical Raman spectroscopy proves conclusively that the near-UV spectrum is anomalous and that PLP is bound to Y225F as a Schiff base: (1) A strong cofactor peak at 1630 cm-1 in the holoenzyme-minus-apoenzyme difference spectrum of the unprotonated form of Y225F is red-shifted by 18 cm-1 in enzyme labeled with 15N at lysine 258 and other positions. (2) This isotope-induced red shift is similar to that observed in the unprotonated form of the model Schiff base, PLP-valine. (3) The Raman spectrum of Y225F is unchanged in H(2)18O, while peaks at ca. 1670 cm-1 in the spectrum of free PLP or in that of a mutant of AATase in which Lys 258 is replaced with Ala, are red-shifted by ca. 30 cm-1 in H(2)18O.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347610 TI - Influence of chemistry in immobilization of cobra venom phospholipase A2: implications as to mechanism. AB - Phospholipase A2 from Naja naja kaouthia venom was covalently coupled onto agarose beads using two different chemistries. The effect of micellar competitive inhibitors in the coupling media was evaluated. Enzyme bound to N hydroxysuccinimide-activated agarose, which is reactive primarily toward epsilon amino groups, had 20% activity retention against micellar diheptanoylphosphatidylcholine (DiC7-PC). Enzyme bound through carboxylic groups, using a modification of the carbodiimide method, had 50% retention. Similar relative activities were observed, for both conjugates, in monomeric dihexanoyl PC and in mixed micelles of Triton X-100 with dipalmitoyl-PC or dioleoylphosphatidylethanolamine. The soluble form of the enzyme showed premicellar activation against monomeric DiC7-PC, while the immobilized form showed interfacial recognition at concentrations around the critical micellar concentration. These results suggest that the enzyme activity lost upon immobilization is a result of the inherent chemical modification of the enzyme and that enzyme oligomerization and interfacial recognition are not cause-effect phenomena. PMID- 8347611 TI - Catalysis of a protein folding reaction: thermodynamic and kinetic analysis of subtilisin BPN' interactions with its propeptide fragment. AB - The in vivo folding of subtilisin is dependent on a 77 amino acid propeptide, which is eventually cleaved from the N-terminus of subtilisin to create the 275 amino acid mature form of the enzyme (Ikemura et al., 1987). We have cloned, expressed, and purified large quantities of the 77 amino acid subtilisin propeptide. This has enabled us to characterize its participation in the subtilisin folding reaction by spectroscopic and microcalorimetric methods. Unfolded subtilisin, when returned to native conditions, is kinetically isolated from its native state. Folding of subtilisin with the native calcium site-A is extremely slow even in the presence of a high concentration of isolated propeptide. The folding of a calcium-free mutant subtilisin, however, is readily catalyzed by the isolated propeptide. The propeptide-subtilisin folding reaction can be described as the following equilibrium: P(u) + S(u)<==>P-S<==>Pf Sf<==>P(u) + Sf, where S(u) and P(u) are subtilisin and propeptide, respectively, which are largely unstructured at the start of the reaction; P-S is a collision complex of unfolded subtilisin and propeptide; Pf-Sf is the complex of folded subtilisin and propeptide; and Sf is folded subtilisin. The rate-limiting step in the folding reaction of calcium-free mutant subtilisin is formation of the initial collision complex, P-S. The rate at which P(u) and S(u) form a productive collision complex is approximately 500 M-1 s-1. The collision complex appears to be an early folding unit which, once formed, results in rapid isomerization to the fully folded complex. The rate constant for isomerization of the collision complex to the folded complex is > or = 0.5 s-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347613 TI - Dimerization of Thermomonospora fusca beta-1,4-endoglucanase E2. AB - Unboiled Thermomonospora fusca endoglucanase E2 electrophoresed on SDS polyacrylamide gels migrated in the range of 80-90 kDa, but when boiled it migrated in the 40-42-kDa range. Sedimentation equilibrium centrifugation as well as chemical cross-linking experiments confirmed that E2 is a dimer. The dimer was reversibly dissociated at low pH. The E2 dimer was stable up to 70 degrees C, but began to dissociate at this temperature after a 30-60-min incubation. A nondimerizing mutant was obtained using region-specific chemical mutagenesis. DNA sequencing of this mutant revealed a single base change that substituted Gly for Glu-263. Chemical modification of carboxylic acid residues in E2 disrupted the dimer interaction. PMID- 8347612 TI - Specificity studies on the heparin lyases from Flavobacterium heparinum. AB - An understanding of the substrate specificity study of the heparin lyases (heparinase and heparitinases) is crucial for elucidation of the sequence of heparin and heparan sulfate. Four chemically modified heparins have been used to study the substrate specificity of the three heparin lyases. These modified heparins include the N- and O-desulfated and then specifically N-sulfated or N acetylated derivatives of heparin and a modified heparin containing L galactopyranosyluronic acid residues. These chemically modified heparins were degraded to various extents by the three heparin lyases. Differences in degree of sulfation have profound impact on the ease of cleavage of glycosidic linkages. Heparin lyase I (EC 4.2.2.7) is selective in cleaving highly sulfated polysaccharide chains containing linkages to 2-O-sulfated alpha-L idopyranosyluronic acid residues. Heparin lyase III (EC 4.2.2.8) cleaves linkages that have reduced density of sulfation and that contain beta-D glucopyranosyluronic acid residues. The ability of heparin lyase III to act on linkages to unsulfated alpha-L-idopyranosyluronic acid residues is observed for the first time. Heparin lyase II (no assigned EC number) demonstrates an unparalleled, wide specificity for substrates comprised of linkages containing both alpha-L-idopyranosyluronic and beta-D- glucopyranosyluronic acid residues. Heparin lyase II can also act on substrates containing linkages to unnatural alpha-L-galactopyranosyluronic acid residues. The high level of specificity of heparin lyase I makes it particularly suitable for use in the sequencing of heparin and heparan sulfate, while caution must be exercised in using heparin lyases II and III to sequence heparin and heparan sulfate because of their relatively broad specificity. PMID- 8347615 TI - Disulfide arrangement and functional domains of beta-1,4-endoglucanse E5 from Thermomonospora fusca. AB - Thermomonospora fusca cellulase E5 contains six cysteine residues. The number and location of the disulfide bonds and the effect of reduction of the disulfides and modification of the resulting half-cystine residues on enzymatic activity were determined. No free sulfhydryl groups were found in E5. Reduction and subsequent labeling with iodoacetamide of E5 and of an enzymatically active 32-kDa proteolytic derivative of E5 (E5cd) showed that one of the three disulfides is accessible to reduction under nondenatured conditions while the other two are not accessible. Full reduction of the disulfides and complete carboxymethylation of the six cysteines decrease the specific activity of E5 on CMC by more than half, but reduction of only the exposed disulfide bond does not affect enzymatic activity or binding of E5 to cellulose. A 14-kDa proteolytic fragment of E5 containing 120 amino acids from the N-terminus of the protein was shown to bind to crystalline cellulose. This confirms earlier evidence that the cellulose binding domain of E5 is located at the N-terminus of the protein. This 14-kDa fragment contains the accessible disulfide bond involving Cys93 and Cys100. The location of the two disulfide bonds in the other fragment (E5cd) was determined by cleaving it with cyanogen bromide under conditions that left the disulfide bonds intact. The resulting peptides were separated under both nonreducing and reducing conditions using RP-HPLC. Amino acid analysis of peptide peaks indicated that one disulfide linkage in E5cd joins Cys138 to Cys143 while the other joins Cys166 to Cys406. PMID- 8347614 TI - Disulfide arrangement and chemical modification of beta-1,4-endoglucanase E2 from Thermomonospora fusca. AB - Thermomonospora fusca endoglucanase E2 contains six cysteine residues scattered along the protein sequence. Four of the cysteine residues were shown to participate in two disulfide bonds while the last two form a third disulfide bond. Neither full reduction of the disulfides nor complete carboxymethylation of all six cysteines totally destroys enzymatic activity, but the activity of the reduced enzyme is much lower than the native enzyme and the iodoacetamide modified enzyme has very low activity. Reduction of only the accessible disulfides drastically decreases the enzyme's thermostability. One disulfide linkage joins Cys80 to Cys125, another joins Cys232 to Cys267, and the third joins Cys315 to Cys407. The first two bonds are similar to those in cellobiohydrolase II, which also belongs to cellulase family B (Rouvinen et al., 1990; Lao et al., 1991; Henrissat et al., 1989). Direct evidence for the involvement of carboxyl groups in catalysis by E2 was demonstrated by chemical modification with carbodiimide. PMID- 8347616 TI - The anion requirement for iron release from transferrin is preserved in the receptor-transferrin complex. AB - Rates of iron release from both sites of free transferrin at pH 7.4 are critically dependent upon ionic strength, because release appears to require binding of a simple nonchelating anion such as chloride to a kinetically active site of the protein. This site is distinct from the synergistic anion-binding site, occupancy of which is required for binding of iron to occur at all. Complexing of transferrin to its receptor also modulates release of iron, but in a more complex fashion. At extracellular pH, 7.4, receptor retards release, but at the pH of the endosome in which release occurs within the cell, 5.6, receptor accelerates release. The present study was undertaken to determine whether the kinetically active anion requirement is maintained at pH 5.6 and whether the effects of anion binding and receptor binding are independent of each other. A spectrofluorometric method was developed to monitor release of iron from C terminal monoferric human transferrin and its complex with the transferrin receptor. At pH 5.6, as at pH 7.4, profiles of iron release to pyrophosphate from free and from receptor-complexed monoferric transferrin show curvilinear dependence on pyrophosphate concentration, consistent with a previously described kinetic scheme and suggestive of a similar release mechanism in all cases. Furthermore, at pH 5.6 release rates depend upon anion (chloride) concentration in free and in receptor-complexed transferrin as in free transferrin at pH 7.4, extrapolating nearly to zero as chloride concentration approaches zero. The enhancing effect of receptor on release is displayed at all concentrations of chloride tested,indicating that the release-promoting effects of receptor and chloride are independent of each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347617 TI - Functional methionines in the collagen/gelatin binding domain of plasma fibronectin: effects of chemical modification by chloramine T. AB - Chemical modification of plasma fibronectin (pFn) or its 40-kDa collagen/gelatin binding (CGB) domain by low concentrations of chloramine T (CT), a methionine specific oxidant, caused decreased binding affinity between pFn or the isolated CGB domain and Sepharose-immobilized denatured collagen or a Texas Red-labeled CNBr fragment CB7 from the alpha 1 chain of type I collagen. Kds obtained by fluid-phase fluorescence polarization binding assays increased upon oxidation about 17-fold for pFn and by 4-fold for the CGB domain. Comparison of CT-oxidized and native CGB domains by endogenous tryptophan fluorescence and CD spectra gave no indication of conformational changes. delta GH2O, the free energy of unfolding at infinite denaturant dilution, derived from guanidinium chloride denaturation curves, differed by less than 0.7 kcal/mol for the oxidized and native CGB domains, indicating essentially equivalent conformational stabilities. We show here that methionyl residues found at positions 412, 432, and 446 are the sites of the oxidative modification. Modification protection experiments carried out in the presence of gelatin demonstrated specific protection of otherwise oxidizable methionyl residues and preservation of high-affinity binding. These results implicate methionyl residues as functional in contributing to high-affinity binding interaction between fibronectin and gelatin. PMID- 8347618 TI - Synthesis and processing of D2 dopamine receptors. AB - Dopamine receptors belong to a superfamily of neurotransmitter receptors that are functionally coupled to guanine nucleotide binding proteins. In this study, we have used Chinese hamster ovary (CHO) cells stably transfected with the rat D2L receptor, in conjunction with specific anti-peptide antibodies that we have developed, in order to visualize this protein and the course of its synthesis. The newly synthesized receptor exists as a 45-kDa protein which undergoes further processing to a 75-kDa glycosylated receptor in the CHO cells. In pulse-chase experiments it was noticed that a 35-kDa precursor was present which disappeared after 30 min. In order to determine whether this 35-kDa protein represents an unprocessed form of the receptor, we have employed an in vitro translation system with cDNA constructs coding for both the murine D2 and D3 dopamine receptor isoforms. In the absence of processing, the D2 and D3 receptors have an apparent molecular mass of 35 kDa. The translated proteins were shown to be the full length receptors by immunoprecipitation with various anti-peptide antibodies and by the demonstration that they can undergo glycosylation to apparent molecular masses of approximately 45 kDa in an in vitro system. PMID- 8347619 TI - Real-time measurements of kinetics of EGF binding to soluble EGF receptor monomers and dimers support the dimerization model for receptor activation. AB - We have tested one aspect of the allosteric dimerization model for the activation of EGF receptor (EGFR) by EGF: whether EGF binding favors dimerization of the receptor. For this to be true, EGF molecules must bind with higher affinity to dimeric receptors than to monomeric receptors. We have tested this directly in a defined system using the soluble, extracellular ligand binding domain of EGFR monomers (sEGFR) and sEGFR dimers stabilized by treatment with a covalent cross linking agent. We describe real-time kinetic measurements of EGF binding to receptor monomers and dimers employing the method of total internal reflection (surface plasmon resonance). Our data show that sEGFR dimers bound EGF with 30-40 fold higher affinity [KD = (2-3) x 10(-8) M] than did sEGFR monomers. The enhanced binding affinity of sEGFR dimers resulted mainly from a reduced off-rate with k(off) = 0.001 s-1 for sEGFR dimers as compared to k(off) = 0.06 s-1 for sEGFR monomers. These measurements indicate that dimerization of sEGFR increases its affinity for EGF by prolonging the amount of time that EGF remains bound to the receptor. This provides evidence that EGF binding stabilizes receptor dimerization and provides further support for the allosteric dimerization model as a mechanism for ligand induced receptor activation. PMID- 8347620 TI - Two upstream cysteines and the CAAX motif but not the polybasic domain are required for membrane association of Xlcaax in Xenopus oocytes. AB - We have analyzed the role of several protein motifs in controlling the membrane association of the xlcaax-1 protein in Xenopus oocytes. Xlcaax-1 is a maternally expressed protein that during development is associated with the basal lateral membrane of polarized epithelial cells. It is enriched in the tubule cells of the adult kidney and several other organs that are involved in osmoregulation. Xlcaax 1 has a C-terminal CAAX sequence (CVVM) identical to that of N-ras, followed by two cysteines that are potential palmitoylation sites and a polybasic domain. Mutants were constructed that either deleted specific domains or changed specific amino acids of the consensus sequences in or near the CAAX motif. Synthetic mRNAs were injected into Xenopus oocytes and their protein products analyzed for their ability to associate with the oocyte plasma membrane. A mutation changing cysteine-588 of the CAAX box to serine or the inhibition of prenylation by lovastatin eliminated the membrane association of the protein. Mutation of either of the upstream cysteines (either 585 or 587) also inhibited the association of xlcaax-1 with the membrane. Unlike Ras, however, deletion of the polybasic domain had no effect on membrane binding. In addition, we show that xlcaax-1 binds ATP but not GTP. PMID- 8347621 TI - pH-dependent association of chromogranin A with secretory vesicle membrane and a putative membrane binding region of chromogranin A. AB - Chromogranin A is a low-affinity, high-capacity Ca2+ binding protein, postulated to be responsible for the Ca2+ buffering role of secretory vesicles, and has been found only in the soluble portions of the vesicular proteins. Contrary to the generally accepted notion of chromogranin A existing as a soluble matrix protein, chromogranin A bound to the secretory vesicle membrane at the intravesicular pH of 5.5 and freed from the membrane when the pH was raised to a more physiological pH of 7.5. Trypsin digestion studies of the vesicle membrane suggested that chromogranin A interacts with the protein component(s) on the intravesicular side of the membrane. Furthermore, in a study using 14 synthetic chromogranin A peptides which represent various portions of chromogranin A, a segment in the N terminal region (residues 18-37) was shown to bind to the vesicle membrane in a pH-dependent manner. The pH-dependent vesicle membrane binding property of chromogranin A appears to be of fundamental physiological importance with regard to the potential roles of chromogranin A in secretory vesicle biogenesis, particularly in segregating secretory vesicle membranes from others in the trans Golgi network, and also in transmitting extravesicular signals such as inositol 1,4,5-trisphosphate or inositol 1,3,4,5-tetrakisphosphate for Ca2+ release or uptake to the inside of vesicles. PMID- 8347622 TI - Interactions of model human pulmonary surfactants with a mixed phospholipid bilayer assembly: Raman spectroscopic studies. AB - The temperature dependence and acyl chain packing properties of the binary lipid mixtures of dipalmitoylphosphatidylcholine-d62 (DPPC d62)/dipalmitoylphosphatidylglycerol (DPPG) multilayers, reconstituted with two synthetic peptides for modeling the membrane behavior of the SP-B protein associated with human pulmonary surfactant, were investigated by vibrational Raman spectroscopy. The synthetic peptides consisted of 21 amino acid residues representing repeating charged units of either lysine or aspartic acid separated by hydrophobic domains consisting of four leucines (KL4 or DL4, respectively). These peptides were designed to mimic the alternating hydrophobic and hydrophilic sequences defining the low molecular weight SP-B protein. Raman spectroscopic parameters consisting of integrated band intensities, line widths, and relative peak height intensity ratios were used to probe the bilayer order/disorder characteristics of the liposomal perturbations reflected by the reconstituted membrane assemblies. Temperature profiles derived from the various Raman intensity parameters for the 3100-2800-cm-1 carbon-hydrogen (C-H) and the 2000 2300-cm-1 carbon-deuterium (C-D) stretching mode regions, spectral intervals representative of acyl chain vibrations, reflected lipid reorganizations specific to peptide interactions with either the DPPC-d62 or DPPG component of the liposome. For the multilamellar surfactant systems composed of either KL4 or DL4 reconstituted with the binary DPPG/DPPC-d62 lipid mixture, the breadth of the gel to liquid crystalline phase transition temperatures TM, defined by acyl chain C-H and C-D stretching mode order/disorder parameters, increased from about 1 degree C in the peptide-free systems to over 10 degrees C. This breadth in TM indicates an increased lipid disorder and a distinct noncooperative chain melting process for the model liposomes. In comparing the interactions of the synthetic peptides with DPPG/DPPC mixtures and with DPPC liposomes alone, the negatively charged DL4 peptide perturbs the DPPG component of the lipid mixture more strongly than the DPPC-d62 component; moreover, the DL4 peptide disrupts the structure of the DPPG lipid domains in the binary mixture to a greater extent than the KL4 peptide. The microdomain heterogeneity of the binary lipid mixture arising from lipid-peptide interactions is discussed in terms of the Raman spectral properties of the multilayers. The Raman data in conjunction with previous bubble surfactometer and animal studies (Cochrane & Revak, 1991) suggest that lipid domain structures are present in functional surfactants and that the dynamic bilayer microheterogeneity induced by the surfactant peptide or protein is essential for pulmonary mechanics. PMID- 8347623 TI - Subunit interactions in the carboxy-terminal domain of phytochrome. AB - We have produced defined fragments of the oat PhyA AP3 protein using an in vitro translation system and analyzed the quaternary structure of these fragments by size exclusion chromatography. Sequences between amino acids S599 and L683 are shown to dimerize by this in vitro assay and by a lambda repressor-based in vivo assay. A subset of this dimerization region, V623-S673, which has previously been identified as being involved in interdomain interactions on the basis of the behavior of overlapping constructs in a lambda repressor assay for protein protein interaction, is shown by both assays to be necessary but insufficient for dimerization. Sequences between L685 and R815, which are unable to dimerize by themselves, are shown to interact with sequences between S599 and L683. Sequences E1069-Q1129, also previously suggested to be involved in dimerization, are shown here not to be required for phytochrome dimerization. These results based on an in vitro assay have confirmed some of the results previously obtained using an in vivo assay and extend these earlier results by revealing new protein-protein interactions. This dissection of sequences involved in phytochrome dimerization taken together with previous work has enabled us to propose a model for the behavior of the dimerization region where the core structure involved in dimerization is located on both sides of a region around residue 750 found at the surface. PMID- 8347624 TI - Rate of oxidation of P680 in isolated photosystem 2 reaction centers monitored by loss of chlorophyll stimulated emission. AB - We have continued our studies of the primary photochemistry of isolated photosystem 2 reaction centers using femtosecond transient absorption spectroscopy. Experiments were performed over a wide range of excitation and probe wavelengths, using several data collection time scales. This has enabled us to resolve five different lifetimes ranging between 100 fs and 200 ps plus a nanosecond component. We demonstrate here and elsewhere [e.g., Durrant, J.R., Hastings, G., Joseph, D. M., Barber, J., Porter, G., & Klug, D. R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11632-11636] that the kinetic spectra associated with all but two of these lifetimes are clearly distinguishable. We have previously reported that a 21-ps lifetime is associated with pheophytin reduction [Hastings, G., Durrant, J. R., Hong, Q., Barber, J., Porter, G., & Klug, D. R. (1992) Biochemistry 31, 7638-7647]. In this paper, we show that it is possible to spectrally and temporally resolve stimulated emission from PS2 reaction centers with great accuracy and that this stimulated emission is largely unaffected by those kinetic components which are faster than 21 ps. The observation of a distinct stimulated emission band allows us to distinguish charge-separated states from chlorin singlet states. In this way, we are able to show that the proportion of charge-separated states prior to the 21-ps component is between 0% and 25%. We also show that the shape of the spectrum which we obtain for the state P680+Ph- is essentially invariant between 100 ps and 9 ns, and is the same as that previously reported for P680+Ph- by other researchers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347625 TI - Synthesis and damage specificity of a novel probe for the detection of abasic sites in DNA. AB - The abasic site (apurinic/apyrimidinic site) is the most common lesion in DNA and is suggested to be an important intermediate in mutagenesis and carcinogenesis. We have recently reported a novel assay for the detection and quantitation of abasic sites in DNA [Kubo, K., Ide, H., Wallace, S. S., & Kow, Y. W. (1992) Biochemistry 31, 3703-3708]. In this assay, the aldehyde group in an abasic site is first modified by a probe bearing a biotin residue, called the Aldehyde Reactive Probe (ARP) and then the tagged biotin is quantified by an ELISA-like assay. However, in the previous study, ARP was prepared only in a crude form, and no solid chemical data concerning the structure and specificity of ARP were reported. In this study, an improved method for the preparative synthesis of ARP has been established, and its structure has been unambiguously characterized using spectroscopic means. In order to elucidate the specificity of ARP to DNA damages, ARP was incubated with a variety of damaged bases or nucleosides and the reaction mixtures were analyzed by HPLC. Of the 14 compounds tested for their reactivity to ARP, 2-deoxyribose (a model compound for an abasic site) and 5 formyluracil reacted with ARP. Interestingly, compounds bearing a formamide group such as formamidopyrimidine and deoxyribosylformamide did not react with ARP, indicating that ARP is specific to damages having an alkyl or allyl aldehyde group. Furthermore, the ability of ARP synthesized by the defined chemical route to detect abasic sites has been substantiated using natural DNA containing abasic sites. Potential applications and limitations of the ARP assay are discussed. PMID- 8347626 TI - Evidence for an imino intermediate in the T4 endonuclease V reaction. AB - Reductive methylation and site-directed mutagenesis experiments have implicated the N-terminal alpha-amino group of T4 endonuclease V in the glycosylase and abasic lyase activities of the enzyme. NMR studies have confirmed the involvement of the N-terminal alpha-amino group in the inhibition of enzyme activity by reductive methylation. A mechanism accounting for these results predicts that a (imino) covalent enzyme-substrate intermediate is formed between the protein N terminal alpha-amino group and C1' of the 5'-deoxyribose of the pyrimidine dimer substrate subsequent to (or concomitantly with) the glycosylase step. Experiments to verify the existence of this intermediate indicated that enzyme inhibition by cyanide was substrate-dependent, a result classically interpreted to imply an imino reaction intermediate. In addition, sodium borohydride reduction of the intermediate formed a stable dead-end enzyme-substrate product. This product was formed whether ultraviolet light-irradiated high molecular weight DNA or duplex oligonucleotides containing a defined thymine-thymine cyclobutane dimer were used as substrate. The duplex oligonucleotide substrates demonstrated a well-defined gel shift. This will facilitate high-resolution footprinting of the enzyme on the DNA substrate. PMID- 8347627 TI - Formation of a cleavasome: enhancer DNA-2 stabilizes an active conformation of NaeI dimer. AB - Cleavage of DNA by NaeI-type restriction enzymes is stimulated by a DNA element with affinity for the activator site of the enzyme: a cleavage-enhancer DNA element. Measurements of the mobility of NaeI activity in comparison with protein standards on gel permeation columns and glycerol gradients demonstrated that NaeI, without enhancer, can form a 70,000 MW dimer. The dimer, however, is inactive: it could not cleave the "resistant" NaeI site in M13mp18 DNA in the absence of enhancer. In cleavage assays, enhancer stimulated either DNA nicking or DNA cleavage, depending upon NaeI concentration, and reduced the NaeI concentration required for the transition from nicking to cleavage activity. A gel mobility-shift assay of the interaction of NaeI with enhancer showed the formation of two complexes. Results using different sized DNAs and different percentage acrylamide gels for gel mobility-shift analysis implied that the two complexes were caused by NaeI monomer and dimer structures rather than one and two DNA binding. Dimer formation increased with the affinity of enhancer for NaeI. UV cross-linking "captured" the NaeI-enhancer complex; electrophoretic analysis of the cross-linked products showed NaeI dimer bound to enhancer. These results imply a model for cleavage enhancement in which enhancer binding stabilizes an active NaeI dimer conformation ("cleavasome") that cleaves both DNA strands before dissociating. PMID- 8347628 TI - Assignment of 1H, 15N, and backbone 13C resonances in detergent-solubilized M13 coat protein via multinuclear multidimensional NMR: a model for the coat protein monomer. AB - The major coat protein (gVIIIp) of bacteriophage M13 complexed with SDS detergent micelles was used as a model system to study the lipid-bound conformation of the protein. Conditions were found that allowed the recording of good quality of NMR spectra. By making extensive use of three-dimensional heteronuclear (13C, 15N) NMR, we obtained a complete set of resonance assignments for 1HN, 1H alpha, 1H beta, 13C alpha, CO, and 15N and partially assigned the rest of the 1H spectrum. Analysis of NOE and chemical shift data reveals that gVIIIp is composed of two alpha-helical domains, one ranging from Pro-6 to Glu20 and the other ranging from Tyr-24 all the way to the C-terminus Ser-50. In contrast to the results reported by Henry and Sykes [Henry, G.D., & Sykes, B.D. (1992) Biochemistry 31, 5285 5297], at a high SDS to protein ratio the protein appears to be monomeric. PMID- 8347630 TI - Isoprenoid diphosphate utilization by recombinant human farnesyl:protein transferase: interactive binding between substrates and a preferred kinetic pathway. AB - The catalytic utilization of dimethylallyl, geranyl, farnesyl, and geranylgeranyl diphosphates in the reaction catalyzed by recombinant human farnesyl:protein transferase (hFPTase) has been examined in the presence of three different protein substrates, Ras-CVLS, Ras-CVIM, and Ras-CAIL. hFPTase catalyzed both farnesylation and geranylation of Ras-CVLS and of Ras-CVIM but not of Ras-CAIL. Geranylgeranylation was observed, but only when Ras-CVIM was the acceptor substrate. Steady-state initial velocity and dead-end inhibitor studies indicate that hFPTase-catalyzed geranylation, like bovine FPTase-catalyzed farnesylation, proceeds through a random order, sequential mechanism. Surprisingly, however, Michaelis constants for a given protein acceptor substrate varied depending upon which isoprenoid diphosphate was used as the donor substrate, showing that these substrates do not bind independently to the enzyme (under catalytic conditions). In addition, at very high concentrations of Ras-CVIM, substrate inhibition was observed in the presence of both FPP and GPP. Isotope partitioning studies showed that, at high concentrations of Ras-CVIM, more than 80% of the bound farnesyl diphosphate (FPP) can be trapped as product, suggesting that the binary complex is catalytically competent and that the ternary complex proceeds to product faster than it releases FPP. The release rate of FPP from the binary complex was calculated to be 0.05 s-1, which is only about eight times greater than kcat. Thus, the binding of FPP to the enzyme in the presence of the protein substrate is not an equilibrium situation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347629 TI - Novel heteronuclear methods of assignment transfer from a diamagnetic to a paramagnetic protein: application to rat cytochrome b5. AB - 15N and 1H resonance assignments for backbone and side-chain resonances of both equilibrium forms of rat ferricytochrome b5 have been obtained, using a combination of novel heteronuclear assignment transfer methods from the known assignments of the diamagnetic protein [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375] and computational methods which depend on an accurate determination of the orientation of the components of the susceptibility tensor. The transfer of amide proton resonance assignments takes advantage of the apparent insensitivity of amide 15N resonances to pseudocontact effects, evident in overlays of 15N-1H heteronuclear correlation spectra. Amide-proton resonance assignments tentatively transferred from the known diamagnetic assignments to the paramagnetic form of the protein were confirmed using conventional assignment strategies employing 600-MHz COSY, HOHAHA, and NOESY spectra of the oxidized protein. As was observed in rat ferrocytochrome b5, more than 40% of all residues exhibited NMR detectable heterogeneity due to the two different orientations of the heme. Complete assignment of both forms enabled accurate determination of the orientation of the susceptibility tensor for both conformations of the heme. The orientation of the z-component of the susceptibility tensors for the two forms are indistinguishable, while the in-plane components appear to differ by about 6 degrees. Differences in the orientation of the in-plane susceptibility components are undoubtedly due dominantly to the relative axial rotation of the heme of between 5 degrees and 10 degrees indicated by the NOESY contacts to the protein observed in the spectra of the ferrocytochrome [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375; Pochapsky, T. C., Sligar, S. G., McLachlan, S. J., & LaMar, G. N. (1990) J. Am. Chem. Soc. 112, 5258-5263]. PMID- 8347631 TI - Activation of the silent progesterone receptor gene by ectopic expression of estrogen receptors in a rat fibroblast cell line. AB - We describe the construction and characterization of a novel estrogen (E2) responsive cell line, Rat1+ER, which ectopically expresses estrogen receptor (ER). Human ER cDNA was introduced by retrovirus-mediated gene transfer into the Rat1 cell line, which does not express functional ER endogenously. Rat1+ER cells express functional ER based on radioreceptor assays, immunoblotting, and transient transfection experiments using E2-responsive reporter plasmids. The effects of this ectopic ER expression were studied on three endogenous E2 responsive genes, prolactin (PRL), progesterone receptor (PR), and epidermal growth factor receptor (EGFR). PRL, usually expressed in the lactotrophs of the pituitary, is not expressed at all in Rat1+ER cells, with or without E2 addition, and appears to require other factors for expression. In contrast, although PR is not expressed in Rat1 cells, it is induced in Rat1+ER cells upon the addition of E2. This induction appears to occur at the transcriptional level and is insensitive to cycloheximide treatment. This is one of the few examples where the expression of one gene activates an otherwise silent gene. Another contrasting observation is that, although EGFR is basally expressed in Rat1+ER cells, the addition of E2 has no effect. Our studies paint a complicated picture of E2 regulation of endogenous genes: the activation of the PR gene may only require the presence of E2 and ER, whereas EGFR and PRL genes require factors in addition to ER for basal as well as E2-regulated expression. PMID- 8347633 TI - Role of prenylation in the interaction of the a-factor mating pheromone with phospholipid bilayers. AB - We have studied the interaction between phospholipids and a-factor (YIIKGVFWDPAC [Farn]OMe), S-alkylated forms of a-factor with the farnesyl group substituted by methyl, hexadecanyl, or benzyl groups, and truncated forms of this lipopeptide. Circular dichroism studies suggest that, despite its lack of farnesylation, S methyl-a-factor is incorporated into vesicles of dimyristoylphosphatidylcholine in a conformation similar to that which a-factor adopts in this membrane. However, studies of the intrinsic fluorescence of the Trp residues of these peptides indicate that this residue is more deeply imbedded into the bilayer in the case of the farnesylated peptide. The a-factor is more effective in raising the bilayer to the hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine than is the S-methyl-a-factor. This bilayer stabilizing ability is also reflected in a-factor inhibiting leakage from vesicles of N-methyldioleoylphosphatidylethanolamine. Studies on a-factor analogs permit the conclusion that the bilayer-stabilizing effect of a-factor is not solely a consequence of its greater partitioning into the membrane but is also a consequence of the degree of penetration into the bilayer and the specific conformation of the peptide at the membrane interface. These results indicate that the farnesyl group alone, in the absence of cellular factors, bestows a particular physical interaction with membranes. PMID- 8347632 TI - The chemical step is not rate-limiting during the hydrolysis by phospholipase A2 of mixed micelles of phospholipid and detergent. AB - The effect of detergents on the overall catalytic turnover by secreted phospholipase A2 (PLA2) on codispersions of the substrate phospholipid is characterized. The overall rate of interfacial catalytic turnover depends on the effective substrate "concentration" (mole fraction) that the bound enzyme "sees" at the interface. Therefore, besides the intrinsic catalytic turnover rate determined by the Michaelis-Menten cycle in the interface [Berg et al. (1991) Biochemistry 30, 7283], two other interfacial processes significantly alter the overall effective rate of hydrolysis: first, the fraction of the total enzyme at the interface; second, the rate of replenishment of the substrate. At low mole fractions (< 0.3), bile salts promote the binding of pig pancreatic PLA2 to zwitterionic vesicles, and the rate of hydrolysis increases with the fraction of the enzyme in the interface. At higher (> 0.3) mole fractions of the detergent, the bilayer is disrupted, and the rate of hydrolysis decreases by more than a factor of 10. The detergent-dependent decrease in the rate of hydrolysis of the sn-2-oxyphospholipids is much larger than that of sn-2-thiophospholipid, and therefore the element effect (O/S ratio) decreases from about 10 in bilayers to less than 2 in mixed micelles. This loss of the element effect in mixed micelles shows that the chemical step is no longer rate-limiting during the hydrolysis of mixed micelles formed by the disruption of vesicles by the detergent. Such effects were observed with phospholipase A2 from several sources acting on substrates dispersed in a variety of detergents including bile salts, 2 deoxylysophosphatidylcholine, and Triton X-100.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347634 TI - Contributions of hydration and steric (entropic) pressures to the interactions between phosphatidylcholine bilayers: experiments with the subgel phase. AB - The total repulsive interaction between electrically neutral, fluid bilayer membranes is thought to have a number of components, including a hydration pressure, due to the reorientation of water by the bilayer, and steric (entropic) pressures due to bilayer undulations, head group motion, and molecular protrusions. For fully hydrated, crystalline bilayers these three steric pressures should be relatively small, and the major repulsive pressure present should be the hydration pressure. Therefore, to isolate the contribution of hydration pressure to the total interbilayer interaction, we have measured pressure-distance data by X-ray diffraction analysis of osmotically stressed dipalmitoylphosphatidylcholine (DPPC) multilayers in the subgel phase, where wide angle and low-angle X-ray data show the bilayers are crystalline. As applied pressure was increased from 0 to 1 x 10(6) dyn/cm2, the interbilayer fluid space (df) decreased less than 1 A from its value at full hydration of 8.4 A. As the pressure was increased from 1 x 10(6) to 3 x 10(7) dyn/cm2, df decreased from about 8 to 4 A. For this range of df, the repulsive pressure decayed exponentially with df with a decay length of 1.4 A. Further increases in applied pressure did not appreciably decrease df, so that there was a sharp upward break in the pressure-distance curve at an interbilayer spacing of about 3 A. In contrast, pressure-distance relations for gel (L beta') phase and liquid crystalline (L alpha) phase bilayers had much softer upward breaks at df < 5 A and extended to larger df at zero applied pressure. However, the pressure distance curves for all three phases decayed exponentially with approximately the same decay length for 4 < df < 8 A. We interpret these data to mean the following: (1) the repulsion observed for df < 5 A is primarily a steric pressure whose range depends on head group motion; (2) the steric undulation pressure plays an important role in determining the hydration properties and the range of the total repulsive pressure for fluid membranes; (3) the same underlying mechanisms govern the repulsive pressure for all phases for 4 < df < 8 A; (4) these mechanisms include a pressure due to reorientation of water molecules; and (5) the hydration pressure component extents a maximum of about two water molecules from the bilayer surface for the subgel phase. PMID- 8347635 TI - Does American acculturation affect outcome of Mexican-American teenage pregnancy? AB - The purpose of this study was to determine whether pregnant Mexican-American teenagers who are acculturated to American lifestyles have different medical and psychosocial problems from those who are more recent immigrants. Consecutive pregnant Mexican-American (or Mexican) teenagers attending a university obstetrics clinic for teenagers were divided into two groups based on country of birth of parents and teen, citizenship, preferred language, and years of U.S. residence. There were 60 in the acculturated group (G1) and 56 in the recent immigrant group (G2). Acculturated teenagers were younger at first sexual intercourse, completed more years of schooling, and sought earlier prenatal care (p < 0.05 for all above). Both groups delivered full-term singletons of average birth weight (mean = 3337 g +/- 477 g). All G2 fathers were Mexican, older (p < 0.05), more likely to be married to G2 teens (p < 0.001), and employed (p < 0.01). The G1 fathers completed more years of schooling (p < 0.05), and 10% were non-Mexican. These data underscore the need to consider acculturation, as well as ethnicity in understanding the experience of pregnant teenagers. PMID- 8347636 TI - Self-efficacy and intent to use condoms among entering college freshmen. AB - We examined self-efficacy theory's ability to explain adolescents' intent to use condoms. In this study, 673 males and 404 females (mean age, 17.8 years) about to begin college, completed health surveys measuring self-efficacy regarding condom use. Perceived self-efficacy differed by gender and sexual experience. Regression analysis demonstrated that frequency of past condom use, perceived ability to talk with new partner about condoms and to enjoy sex using condoms explained 16% of sexually active males' intent to use condoms (p < 0.05). For sexually active females, explanators included frequency of past use and perceived ability to enjoy sex with condoms (R2 = 29.8%, p < 0.05). For never sexually active males, perceived ability to convince partner to use condoms and to buy condoms explained 16.1% of intent (p < 0.05); among never sexually active females, only perceived ability to convince partner to use condoms was significant (R2 = 6.2%, p < 0.05). Efforts to increase condom use should enhance perceptions of ability to negotiate aspects of condom use. PMID- 8347637 TI - Contraceptive self-efficacy in college women. AB - We examined the relationship between the theory of self-efficacy and its effect on contraceptive use along with other variables in a predominantly white female college population. Written survey questionnaires were administered to 356 subjects in college classrooms; the study sample was limited to those 250 female subjects who were age 17-25 years unmarried, and sexually active. The questionnaire was designed to measure contraceptive use, contraceptive self efficacy, demographic variables, and other variables associated with the college psychosocial environment (i.e., alcohol use, history of sexual assault, and future orientation in education and career plans). Contraceptive self-efficacy (CSE) was highly correlated with effective use (r = .4, p < 0.01). Highly effective contraceptive users had a significantly higher mean CSE score (p < 0.01) than that of less effective users. Logistic regression analysis of effective contraceptive use resulted in a four-factor model that correctly classified 76.3% of users. Contraceptive self-efficacy was the most important predictor of contraceptive use for this sample. Lack of barriers to contraception was also important, with knowledge and length of time of sexual activity also included in the final regression model. Most demographic and future orientation variables were not significantly associated with effective use; variables measuring sexual experience and personal attitudes and perceptions about birth control were more significantly associated with effective use. A lack of interference from alcohol was highly associated with effective contraceptive use. Self-efficacy would seem to be important in predicting contraceptive use and effecting behavior change. PMID- 8347638 TI - Prevalence and longitudinal study of breast masses in adolescents. AB - This study examined the prevalence and outcome of breast masses in adolescent females and compared these teens to those without breast masses. A longitudinal study of adolescents with breast masses was conducted from October 1984 through January 1990. The prevalence of discrete breast masses in the 13-month study period was 13/400 (3.25%) among new female patients. The mean length and width of the masses were 2.8 and 1.9 cm; 86% had a solitary mass. Of 61 diagnosed with breast masses, 39 were followed for up to 40 months (mean, 7 months). Teens with a mass were older (16.8 versus 15.1 years, p < 0.001) and had a greater chance of a family history of breast disease (26% versus 10.5%, p < 0.05) than those without a breast mass. Of 39 teens returning for at least one follow-up visit, 10 had a clinical diagnosis of "fibrocystic changes." Of these, the lesions resolved in six. Of the 29 teens with a discrete mass on examination, 7 underwent surgery and were found to have fibroadenomas. Nine of the 29 teens had masses which resolved over 1-12 months, six teens had masses which remained unchanged over 3 40 months, while four had masses which became smaller, and two had masses which became larger. One teen with mastitis improved. Eighteen underwent ultrasonographic examination at the breast. Of the 12 teens found to have a solid mass on ultrasound, none had a mass that resolved on follow-up examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347639 TI - Risks among inner-city young teens: the prevalence of sexual activity, violence, drugs, and smoking. AB - Boston University's Youth at Risk (URISK) program is working to reduce five high risk behaviors: violence, sexual activity, drinking, illicit drug use, and smoking, among inner-city public middle-school students, grades 6-8. To set program priorities and for subsequent program evaluation, students in four schools completed a self-report questionnaire. Violence (physical fighting or carrying a knife or a gun) and sexual activity were the most commonly reported risks, 54% and 38%, respectively, for such activity within the past year. Four fifths of the students reported risk in at least one of the five risk categories at some time; two-thirds reported current risk in at least one category. Among those reporting two or more current risks, over 90% included violence, and over 80% included sexual activity. Except for smoking, risk rates were lower in females than in males. Risk rates for violence and drug use were similar among blacks and whites, while sexual activity was more common and drinking and smoking less common among blacks compared with whites. Rates for all high-risk behaviors were consistently lower for Hispanics than non-Hispanic whites. Risk rates for violence were similar for grades 6-8. Sexual activity increased mainly from the 7th to the 8th grade. Drinking increased both from the 6th to the 7th grade and again from the 7th to the 8th grade. Drug use and smoking increased only from the 6th to the 7th grade. PMID- 8347640 TI - Substance use among youth seen at a community-based health clinic. AB - Despite recent surveys reporting a decline in adolescents' use of alcohol and other drugs in the general population, substance abuse may actually be increasing among particular subgroups of high-risk youth. This study examined the prevalence of alcohol and other drug use reported by 1121 youth, ages 12-24 years, seen for an initial medical visit at a free community-based primary health clinic. The clinic, located in the Hollywood/Wilshire area of Los Angeles, serves both homeless (62%) and non-homeless (38%) youth. Bivariate and multivariate analyses revealed that the homeless youth were significantly more likely to report use of alcohol and illicit drugs (marijuana, stimulants, hallucinogens, and narcotics) and prior involvement in injecting drug use (IDU). Variables found to be significantly associated with substance use among the homeless youth included length of time homeless, an attempted suicide, physical and sexual abuse, and involvement in survival sex/prostitution. Among the non-homeless youth, age of first intercourse, a previous suicide attempt, and a history of physical and sexual abuse were significantly associated with substance use. These findings suggest that rates of alcohol and other drug use may be higher among youth seen at community-based primary health clinics, particularly homeless youth underscoring the need for screening for these risk variables. PMID- 8347642 TI - The evaluation of targeted outreach in an adolescent HIV/AIDS program. AB - PURPOSE: Most HIV infected youth are unaware of their serostatus. Among adolescents who know they are HIV positive, only a small percentage are currently receiving care in age-specific programs. Establishing effective links between prevention and service programs is critical in reaching this group of young people. METHODS: A specific outreach strategy was designed to develop more referrals from a wider variety of agencies to better serve youth at risk for HIV. A needs assessment of community-based agencies was the basis for: 1. overcoming barriers to care, 2. specifying the target population, 3. assessing existing referrals, and 4. selecting agencies for different levels of intensity of outreach. RESULTS: Six barriers faced by potential referring agencies were identified and corresponding solutions created which were incorporated into the outreach strategy. A comparison was made of referrals in the years before, during and after the outreach strategy was instituted. A significant difference by (chi 2 analysis) was noted in the number of agencies (p < 0.05), number of individuals (p < 0.01), number of appointments kept (p < 0.01), and the number of HIV+ youth enrolled (p < 0.01) during the year when the plan was fully implemented compared to previous and subsequent years. CONCLUSIONS: Systematic targeted outreach programs are an efficient way to maximize the time and effort of outreach staff. The result was an increase in the number and diversifity of referrals. This strategy could be used by groups caring for adults or younger children who want to expand services to include adolescents or by groups providing HIV/AIDS care who want to specifically serve adolescents. PMID- 8347641 TI - Crack cocaine use and high-risk behaviors among sexually active black adolescents. AB - The recent spread of crack cocaine use among inner-city teenagers has been accompanied by dramatic increases in juvenile delinquency and sexually transmitted diseases (STDs) among teenagers. This study examined the prevalence of five factors which promote STDs, including human immunodeficiency virus (HIV), among a sample of sexually active black adolescent crack users and non-users from the San Francisco Bay Area. Significant differences were observed between these groups with respect to history of engaging in sexual intercourse under the influence of drugs or alcohol, exchanging sexual favors for drugs or money, condom use in the most recent sexual encounter, and having five or more sexual partners in the last year. Approximately 63% of all respondents reported engaging in at least one of these risk behaviors. In multiple logistic regression analysis, reporting one or more of these STD/HIV risk behaviors was significantly associated with crack use and having one or more relatives who used drugs. Intervention efforts need to address both individual and environmental risk factors in order to reduce teens' risk for STDs, including HIV. PMID- 8347643 TI - Adolescent health services in North Carolina's local health departments. AB - The purpose of this study was to assess availability of clinical health services and special adolescent health programs for those aged 10-19 years administered by local health departments in North Carolina, and to evaluate factors that were associated with the existence of specialized adolescent programs, comprehensive services, and school services. We used self-report surveys mailed to 100 county health directors. All counties responded. One in five (21%) North Carolina youth received one or more health department service in 1990. Thirty-four health departments have programs or services specifically designed for adolescents; 7 health departments provide comprehensive services. The majority of health departments (85%) provide services in public schools, most often health education or counseling. Counties with more adolescents and with higher per capita income were more likely to have adolescent programs and more likely to provide comprehensive clinics. Health departments with school services served proportionally twice as many of their county's adolescents as those without school services. We concluded that few local health departments in North Carolina provide comprehensive health services to their youth. Community-wide participation and state support are needed to improve public sector access to comprehensive health care for adolescents in North Carolina and in other states with decentralized, county-controlled public health systems. PMID- 8347644 TI - Racial differences in blood pressure among urban adolescents. AB - The purpose of this study was to determine if there are racial differences in the blood pressure patterns among urban adolescents. Blood pressure (BP) was measured according to Task Force guidelines in health-screening and education sessions conducted in urban public and parochial high schools. The prevalence of BP > or = 95th% (HBP) on initial screening was determined in a population of 3,349 students. Differences in prevalence of HBP among race, sex, and age groups were tested for significance by chi 2 analysis. The overall prevalence of HBP in this urban adolescent population was 8.1%. Significant race differences were present in females (blacks = 6.6% versus non-Hispanics = 2.9%, p < 0.01). Within the black females, HBP occurred more frequently among the girls attending predominantly black public schools (7.7%) compared to an interracial parochial school (2.0%) p < 0.001. This difference could not be explained by weight, height, or the occurrence of obesity. The observed BP differences within black females, by school, may reflect a family-environment effect on cardiovascular risk. PMID- 8347646 TI - Anterior sacral meningocele presenting as a pelvic/abdominal mass in a patient with Marfan syndrome. PMID- 8347645 TI - Preliminary findings on the effects of sex hormones on bone metabolism in anorexia nervosa. AB - We performed tetracycline double-labeled bone biopsies and serial bone densitometry on four patients with anorexia nervosa to determine the effects of various conditions of sex hormone replacement and body weight status. We found negligible bone mineral apposition rate in two patients with anorexia nervosa who were taking estrogen and progestin pills while weighing only 79% of normal. However, bone mineral apposition rate was normal in two patients with anorexia nervosa who took no sex hormones and remained amenorrheic while weighing 87% of normal. Histomorphometric analysis revealed a decrease in intracortical trabecular area by 57% and an increase in active osteoblastic surface area by 300%, comparing the subjects who were taking hormone replacement to those who were not. There was no direct evidence of increased resorption in any subject. Six months after biopsy, the two subjects taking sex hormones decreased lumbar bone mineral density by 1.9%, while the two taking no sex hormones remained amenorrheic, but increased bone mineral density by 1.3%. Therefore, we propose that sex hormone therapy in the presence of persistently low body weight might be of limited benefit for bone mineral apposition and density. PMID- 8347647 TI - Pervasive developmental disorders: a hidden disability in adolescence. PMID- 8347648 TI - A study of the sexual behavior of teenagers in south Brazil. AB - A study of sexual behavior among teenagers was carried out in a random sample of 884 second degree school (high school) students of Porto Alegre (South Brazil) by means of a self-report questionnaire. The students' ages ranged from 13 to 22 years old, and 59% of them were females. The students believed themselves well informed about physiologic phenomena involved in human reproduction (95.2%; 95% confidence interval (CI):93.5-96.5) and sexually transmitted diseases (STD) (82.1%; 95% CI:79.1-84.7). In addition, 42.4% (95% CI:39.0-45.8) said that they has had a sexual relationship. However, 51.5% (95% CI:45.9-57.0) did not use contraceptive precautions systematically, and 12% (95% CI:7.2-19.0) of girls had already undergone an abortion. Considering these results, it is important to stimulate programs for sexual education strictly focused on teenagers. PMID- 8347649 TI - Factors associated with preterm delivery among pregnant adolescents. AB - The purpose was to identify characteristics of pregnant adolescents associated with preterm delivery. We studied 126 poor, black, 12 through 18-year-old pregnant adolescents and compared the prevalence of potentially high-risk maternal characteristics and obstetric complications in those who bore preterm and term infants. Of the adolescents studied, 12 (9.5%) delivered prematurely. Five maternal characteristics--conception within 3 years of menarche, a low body mass index, a past history of physical or sexual abuse, a socially deviant father of the baby, and vaginal bleeding during the first 8 weeks of gestation--were associated with preterm delivery. A theoretical model is proposed and the therapeutic implication of the study findings. PMID- 8347650 TI - Impact of computerization on nursing: automated order entry, care planning, and implications for recruitment. AB - Very few empirical studies have been completed which verify the actual benefits of automation for nursing. This article provides an overview of the results and implications of five research studies undertaken at a Canadian Hospital to ascertain the impact of computerization on selected aspects of nursing. These studies found that nurses perceived few positive benefits for direct care givers when order entry, results reporting and care planning were automated. This article will be of particular interest to nurse administrators who are embarking on automation within their hospitals. PMID- 8347651 TI - Computerized hospitals: an attraction or deterrent to recruitment in nursing? AB - This article describes a survey of 202 nursing recruits at an 850 bed hospital newly computerized with an Integrated Hospital Information System (IHIS). The nurses answered questions concerning their demographic characteristics, their experience with computers, their attitudes to computers and whether the fact that the hospital was computerized affected their decision to apply for employment. Results of this study suggest that the nurses' decision to apply to this setting for employment did not depend upon the factor of computerization. The majority of recruits held positive attitudes towards computers and it appeared that nurse recruits might be part of an ever increasing computer-literate population. Those having less experience with computers indicated greater anxiety. Implications for recruitment strategies and education are that while no major deterrents may exist for recruitment, new nurses with no computer experience require special attention because they may have higher levels of anxiety about computers. In orientation they may need clarification of what computers can be expected to do in a nursing environment so that they do not form unrealistic expectations. They may need to be informed as to whether a hospital is using a more general Hospital Information System which serves the needs of all departments, or a Nursing Information System which is more closely directed to the nurses' own daily work, since it is the latter which will most affect their degree of contact with computers. PMID- 8347652 TI - A risk management approach to the security of hospital information systems. AB - Risk management in today's technologically advanced health care system demands proactive rather than reactive strategies. Risk management is defined as a planned program for liability control and involves the identification, analysis and evaluation of legal risks followed by strategies to reduce or eliminate these risks. The concept of risk management is most often associated with quality assurance and direct patient care activities. For current purposes, the risk management concept is borrowed from arena of patient care and applied to the security measures surrounding hospital information systems. In this context, risk management/liability control is viewed as proactive activities designed to protect both the hospital information system and the confidentiality of patient information. PMID- 8347653 TI - The policy & procedure manual: development of a computer-assisted process for review. AB - This article documents the successful development of a computer-assisted process for systematic review of nursing policies and procedures at The Queen Elizabeth Hospital, Toronto, Ontario. Through broad staff input, policies and procedures are research-based yet grounded in the reality of the facility's nursing practice. Client-related standards are written as measurable, realistic statements of desired client outcomes, and as such are standards for client care. Policies and procedures have been rated according to the Canadian Council on Health Facilities Accreditation criteria (client centered, high risk, high volume, problem prone, interservice, outcome-related), so that important policies are easily identified to provide focus for quality assurance activities. The review process is structured so that over the course of a year, all policies are circulated for review by all levels of nursing staff. PMID- 8347654 TI - Nursing informatics can streamline nursing care. PMID- 8347655 TI - A Canadian nursing minimum data set: a major priority. AB - Through a selected review of existing hospital and health care minimum data sets in the United States, the United Kingdom and Canada, the authors expose the nursing data gaps in those data sets. Nurses in the United States have responded to these data gaps through the development of a Nursing Minimum Data Set (NMDS). The NMDS is a tool for abstracting a uniform collection of essential nursing data from the patient record usually at hospital discharge. The nursing care data elements in the NMDS include: nursing diagnosis, nursing intervention, nursing outcome, and intensity of nursing care. A major factor influencing the move to generate an NMDS in Canada is the response to the need to contain rising health care costs while maintaining quality health care. The NMDS has profound implications for nurses in all practice settings through use of these data in: costing of nursing services; defending resource allocation to nursing; defining nursing's contribution to patient care; defining outcomes of nursing care; developing nursing knowledge; and continued growth of nursing as a profession. Initiatives in Canada directed at the development of an NMDS indicate a heightened awareness of the need for the collection, storage and retrieval of nursing data. However, nurses in Canada have yet to define the essential nursing data elements for inclusion in a national health information system for use in Canada. PMID- 8347656 TI - Thyroid hormone action on mitochondrial energy transfer. PMID- 8347657 TI - The ferredoxin:sulphite reductase gene from Synechococcus PCC7942. AB - The structural gene of the ferredoxin:sulphite reductase (EC 1.8.7.1) from the cyanobacterium Synechococcus PCC7942 (formerly 'Anacystis nidulans') was cloned and sequenced. The gene termed 'sir' was detected by heterologous Southern hybridisation with the structural gene cysI from Escherichia coli encoding the iron-sulphur haemoprotein of the NADPH:sulphite reductase. The open reading frame is comprised of 1875 bp encoding for a polypeptide of M(r) 70.028. The deduced amino acid sequence is 35.6% identical with the enterobacterial iron-sulphur haemoprotein. This putative fd-dependent sulphite reductase is only distantly related to the fd-dependent nitrite reductase (binary matching coefficient SAB: 0.23) or with the NADPH-sulphite reductase (SAB: 0.32). Highly conserved residues are found within the two Cys clusters forming the reactive Fe4S4-sirohaem centre of the enzyme. Expression of the sir gene using a fusion vector gave a single gene product which is immunologically related with the fd-sulphite reductase from the wild-type bacterium. PMID- 8347658 TI - Functional stability of the a-subunit of the F0F1-ATPase from Escherichia coli is affected by mutations in three proline residues. AB - Site-directed mutagenesis was used to investigate the roles of three proline residues (Pro-103, Pro-122 and Pro-143) in the a-subunit of the E. coli F0F1 ATPase. All three were found to have a role in stabilizing the a-subunit structure in that removal of the F1-ATPase from membranes prepared from each of the mutant strains resulted in the loss of passive proton translocation activity. Pro-103 is predicted to be within a transmembrane helix. Pro-122 and Pro-143 are located just outside the membrane and near two residues (Asp-124 and Arg-140) previously proposed to form a charge pair. The phenotype of mutants in which Pro 122 or Pro-143 were replaced by alanine was similar to previously isolated mutants affected in Asp-124 and Arg-140. This suggested that the main effect of the mutations was to destroy the charge pair between Asp-124 and Arg-140. Double mutants resulting from all possible combinations of these four mutations were constructed and, with the exception of P122A + D124A, had a similar phenotype to the single mutants. This is consistent with the idea that all four single changes had the same effect on a-subunit structure. In contrast, combining the P122A or P143A changes with another mutation which caused a similar phenotype (D44N) resulted in a complete loss of oxidative phosphorylation. PMID- 8347659 TI - Each of three positively-charged amino acids in the C-terminal region of yeast mitochondrial ATP synthase subunit 8 is required for assembly. AB - Each of three conserved positively-charged residues in the C-terminal region of subunit 8 of yeast (Saccharomyces cerevisiae) mitochondrial ATP synthase was replaced with isoleucine. The assembly and functional properties of the resulting variants (substituted at Arg-37, Arg-42 and Lys-47) were examined using in-vitro systems to assay import into isolated mitochondria and to monitor assembly into ATP synthase, as well as an in-vivo rescue system using host yeast cells lacking endogenous subunit 8. Each such variant was found to be impaired in assembly in vitro, after import in the form of a chimaeric protein bearing a leader sequence with mitochondrial targeting function. Import precursors bearing a duplicated leader sequence, engendering enhanced delivery to mitochondria of the passenger variant subunit-8 proteins, enabled assembly of the (Lys-47-->Ile) variant to be detected in vitro but not that of (Arg-37-->Ile) or (Arg-42-->Ile) variants. The respiratory growth of subunit 8-deficient host cells could be rescued with the (Lys-47-->Ile) variant expressed allotopically in the nucleus. Such rescued cells were found to have an enhanced growth rate (comparable to that produced by non mutagenized parental subunit 8) when delivered to mitochondria with the duplicated-leader sequence, as compared to the single-leader sequence. This confirms that the impediment in the (Lys-47-->Ile) variant lies in the efficiency of its assembly, rather than a functional defect, as such, arising from the loss of that positive charge. In contrast, host cells were unable to be rescued by the (Arg-37-->Ile) and (Arg-42-->Ile) variants, even when they were endowed with the duplicated leader sequence. It is concluded that the positively-charged C terminal domain of subunit 8, common to fungal and mammalian homologues of this protein, plays a key role in its assembly into mitochondrial ATP synthase. PMID- 8347660 TI - Binding constants for a physiologic electron-transfer protein complex between methylamine dehydrogenase and amicyanin. Effects of ionic strength and bound copper on binding. AB - Two soluble proteins, methylamine dehydrogenase and amicyanin, form a physiologically relevant complex in which intermolecular electron transfer occurs. To characterize and quantitate the binding of these two weakly associating proteins, an ultrafiltration binding assay has been developed which involves brief centrifugation of mixtures of proteins in centrifuge concentrators followed by quantitation of proteins on each side of the filtration membrane by HPLC. Under low ionic strength conditions which are optimal for the redox reaction between these proteins, a Kd of 4.5 microM was measured for the methylamine dehydrogenase-amicyanin complex. The Kd increased by 8-fold in the presence of added salt. Apoamicyanin, which is known from crystallographic analysis to be structurally very similar to amicyanin, exhibited a much higher Kd and much less specific binding than did the holoprotein. Apoamicyanin also exhibited apparent self-association at low ionic strength which was not observed with amicyanin. These observations are correlated with the known crystal structures of these proteins, free and in complex, and with the available biochemical information on the interactions of these two proteins. PMID- 8347661 TI - Functional characterization of mitochondrial oxidative phosphorylation in saponin skinned human muscle fibers. AB - The conditions of treatment of human skeletal muscle fibers from M. vastus lateralis with saponin were optimized to achieve complete permeabilization of cell membrane at intact mitochondrial oxidative phosphorylation. After 30 min of incubation with saponin all lactate dehydrogenase, 50% of creatine kinase, 30% of adenylate kinase and less than 20% of citrate synthase was released into the permeabilization medium. These skinned fibers behave similar to isolated mitochondria from human skeletal muscle: (i) the respiration with mitochondrial substrates can be stimulated by ADP, (ii) inhibited by carboxyatractyloside and (iii) it is possible to detect fluorescence changes of mitochondrial NAD(P)H on additions of substrates, uncoupler and cyanide. From a comparison of rates of respiration per cytochrome aa3 content of isolated human skeletal muscle mitochondria and saponin-skinned muscle fibers it was possible to calculate that almost 85% of mitochondria in those fibers are accessible for the investigation of oxidative phosphorylation. As shown by the investigation of biopsy samples of two patients with undefined myopathies these fibers are a suitable object for the replacement of isolated mitochondria in the diagnosis of mitochondrial myopathies and encephalomyopathies. PMID- 8347662 TI - Inhibitory effect of NaN3 on the F0F1 ATPase of submitochondrial particles as related to nucleotide binding. AB - The inhibitory effects of NaN3 on the F0F1 ATPase of beef heart submitochondrial particles were investigated. It was shown that NaN3 inhibited the ATPase activity only in the presence of ATP or ADP and the inhibition proceeded slowly. Analysis of the time-course of the inhibition process lead to a conclusion that an ATP binding site which has an apparent Kd of 14.0 +/- 8.7 microM is responsible for the increase of NaN3 sensitivity. This value agreed well with the low Km of ATP hydrolysis characterized before (Muneyuki, E., and Hirata, H. (1988) FEBS Lett. 234, 455-458) and in the range of so-called bi-site catalysis. The same conclusion was derived as for isolated F1 ATPase. From similar analysis, the Kd of this site for ADP was deduced to be 1.34 +/- 0.45 microM, which also agreed with that reported by Pedersen (Pedersen, P.L. (1975) Biochem. Biophys. Res. Commun. 64, 610-616) and also in the same range as reported for the low Km of ATP synthesis by activated submitochondrial particles. These results suggest that hydrolysis through the low Km mode of ATPase reaction leads the enzyme NaN3 sensitive form and this reaction cycle corresponds to the low Km mode of ATP synthesis. PMID- 8347663 TI - Membrane-associated redox cycling of copper mediates hydroperoxide toxicity in Escherichia coli. AB - We are studying the action of tert-butylhydroperoxide (t-BOOH) on Escherichia coli as a model system for peroxide toxicity. In our previous report (De la Cruz Rodriguez, L.C., Farias, R.N. and Massa, E.M. (1990) Biochim. Biophys. Acta 1015, 510-516), the respiratory chain was identified as a major target of t-BOOH. In the present paper, we study further the effect of t-BOOH on the NADH oxidase of the E. coli respiratory chain to clarify the mechanism of damage, especially regarding the identity and role of the metal ion involved. The results are: (a) t BOOH toxicity is mediated by membrane-bound copper ions; (b) a small pool of the membrane-bound copper is reduced from Cu(II) to Cu(I) in the presence of NADH and other respiratory substrates (succinate, D-lactate); (c) this reduction of copper occurs at 37 degrees C but not at 0 degrees C or when the membranes are inactivated by previous heating; (d) the Cu(I) generated by reduction of Cu(II) during membrane preincubation with NADH, is oxidized by t-BOOH with simultaneous inactivation of the NADH oxidase, whereas treatment with only t-BOOH (without NADH) has no effect on the oxidase. It is concluded that the effect of t-BOOH on the respiratory chain is mediated by redox cycling of copper. It is proposed that the damage results from activation of the hydroperoxide through its interaction with Cu(I) in a site-specific Fenton-type reaction. PMID- 8347664 TI - Transport of organic cation in renal brush-border membrane from rats with renal ischemic injury. AB - Transport of tetraethylammonium, an organic cation has been studied using renal brush-border membrane vesicles isolated from rats with ischemic and ischemia reperfusion injury. H+ gradient-dependent uptake of tetraethylammonium slightly, but significantly, decreased in brush-border membrane vesicles from ischemic kidneys. When the kidney was reperfused after ischemia, the extent of the decrease of tetraethylammonium uptake was much greater than that after ischemia alone. The Vmax value of tetraethylammonium uptake by brush-border membrane vesicles from reperfused kidneys was decreased compared with control, without any change in the Km value. The tetraethylammonium uptake by the vesicles from reperfused kidneys was decreases both in the presence and absence of the outward H+ gradient (driving force). Uptake of D-glucose in renal brush-border membrane vesicles was also decreased by ischemia and again, reperfusion caused a further decrease of the uptake. Reperfusion also induced marked changes in the enrichment and recovery of marker enzymes in the isolated brush-border membrane fraction compared with ischemia. These findings suggest that renal ischemic injury altered the transport properties of tetraethylammonium as well as D-glucose, and that reperfusion after ischemia induced further damages on these functions in the brush-border membrane. PMID- 8347665 TI - Voltage-sensitive fluorescence of amphiphilic hemicyanine dyes in neuron membrane. AB - Fluorescent amphiphilic hemicyanine dyes were adsorbed to the plasma membrane of isolated Retzius neurons of the leech. Voltage steps were applied to the neuron by the patch-clamp technique in whole-cell configuration. The change of fluorescence was observed as induced by the voltage jump. The relative changes of the excitation spectrum and of the emission spectrum of fluorescence were recorded. The complete set of spectral data for each dye was fitted by five parameters: shifts of the emission and the excitation spectrum, a change of fluorescence quantum yield and changes of the widths of the excitation and of the emission spectrum. The only common feature for all dyes was a blue-shift of the excitation spectrum and a drop of the yield when the neuron was stained from the outside and a positive voltage was applied to the inside. With respect to the shift of the emission spectrum and the changes of width qualitatively different results were obtained for different dyes. It is not attempted to assign a physical mechanism--probably a superposition of several mechanisms--of voltage sensitivity. PMID- 8347666 TI - The anticancer drug tamoxifen induces changes in the physical properties of model and native membranes. AB - The interactions of tamoxifen with lipid bilayers of model and native membranes were investigated by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and by intramolecular excimer formation of 1,3-di(1-pyrenyl)propane (Py(3)Py). The effects of TAM of liposomes of DMPC, DPPC and DSPC are temperature dependent. In the fluid phase, TAM reduces dynamics of the upper bilayer region as observed by Py(3)Py and has no effect on the hydrophobic region as detected by DPH. In the gel phase, the effects of TAM evaluated by Py(3)Py are not discernible for DMPC and DPPC bilayers, whereas DSPC bilayers become more fluid. However, DPH detects a strong fluidizing effect of TAM in the hydrophobic region of the above membrane systems, where DPH distributes, as compared with the small effects detected by Py(3)Py. TAM decreases the main phase transition temperature but does not extensively broaden the transition thermotropic profile of pure lipids, except for bilayers of DMPC where TAM induces a significant broadening detected with the two probes. In fluid liposomes of sarcoplasmic reticulum lipids and native membranes, TAM induces an ordering effect, as evidenced by Py(3)Py, failing DPH to detect any apparent effect as observed for the fluid phase of liposomes of pure lipid bilayers. These findings confirm the hydrophobic nature of tamoxifen and suggest that the localization and effects of TAM are modulated by the order and fluidity of the bilayer. These changes in the dynamic properties of lipids and the non-specific interactions with membrane lipids, depending on the order or fluidity of the biomembrane, may be important for the multiple cellular effects and action mechanisms of tamoxifen. PMID- 8347667 TI - Induction of lipid-protein mismatch by xenobiotics with general membrane targets. AB - Many membrane-active xenobiotics, such as organic solvents or general anesthetics, are without specific target sites. A common, but as yet ill-defined physical mechanism of action is usually assumed. Displacement of 'boundary' lipid activators from functional membrane proteins by the induction of lipid/protein mismatch is now established as a candidate common physical mechanism. Multiple binding site kinetics demonstrate that xenobiotics can be strongly inhibitory at realistic membrane concentrations of below 4 mol%. A general equation for inhibition is derived. PMID- 8347668 TI - Effects of pH on the activity of the human red cell glucose transporter Glut 1: transport retention chromatography of D-glucose and L-glucose on immobilized Glut 1 liposomes. AB - The facilitative glucose transporter Glut 1 from human red cells was reconstituted into liposomes that were size-fractionated and immobilized in an octyl sulfide-Sephacryl S-1000 column. D-[14C]Glucose was eluted later than L [3H]glucose from the Glut 1 liposome column (by delta V microliters), apparently because the D-glucose was transported through the liposomes. The corresponding difference with protein-free liposomes was delta V0. The Glut 1 transport retention chromatographic effect, delta VG = delta V - delta V0, 40-50 microliters at pH 7, was nearly constant at pH 6-10 (400 mM NaCl, 23 degrees C, internal liposome volume approximately 240 microliters) but decreased steeply below pH 5 to become zero at pH 3.6. The decrease corresponded to a pKa of approximately 4.4 and was partly reversible above pH 4.7. Similarly, glucose exchange by non-immobilized freeze-thawed proteoliposomes with Glut 1 slowed down drastically as the pH was lowered from pH 5.5 to 4; and octyl glucoside solubilized Glut 1 lost half its activity in 15 min at pH 4.5 (low ionic strength, 2 degrees C) as shown by glucose exchange determinations at pH 7.2 The results suggest that Glut 1 is inactivated at low pH upon protonation of carboxylate groups of pKa approximately 4.4-4.8. It seems likely that carboxylate groups form hydrogen bonds to transported D-glucose. PMID- 8347669 TI - Destabilization of egg lecithin liposomes on the skin after topical application measured by perturbed gamma gamma angular correlation spectroscopy (PAC) with 111In. AB - Unilamellar and oligolamellar liposomes were topically applied to the skin of porcine ears. Perturbed angular correlation spectroscopy of 111In-DTPA, initially entrapped into the liposomes, was used to study the release kinetics of the hydrophilic probe. After drying of the liposomal suspensions, a decrease of the time-integrated perturbation factor within 30 min indicated destabilization of the liposomes and total marker release in the upper epidermal layers. PMID- 8347670 TI - Abscisic acid-lipid interactions: a phospholipid monolayer study. AB - Lipid monolayer studies were performed on a Langmuir trough in the absence and in the presence of the plant hormone abscisic acid (ABA). The ABA-induced effects on the lipid monolayers can be summarized as follows: (i) ABA as the free acid (pH below 5.3) increased the molecular area and slightly decreased the surface pressure in the collapse points of monolayers made of saturated, unsaturated and of mixed lipids; ABA as the anion showed only minor effects. (ii) The ABA-induced area increase of the lipid monolayers decreased when the surface pressure increased, but some ABA remained in the monolayers made of unsaturated phospholipids even at collapse pressure. (iii) The incorporation of ABA into the monolayers could be inhibited by adding the plant sterol beta-sitosterol to the monolayer forming phospholipids. (iv) There was no substantial difference of ABA action on plant phospholipids as compared with other phospholipids. (v) ABA had a much stronger influence on unsaturated phospholipids than on saturated ones. (vi) ABA decreased the phase-transition temperature of saturated phospholipids. These results, which agree with those obtained from phospholipid vesicle studies, indicate that the physical state of the lipid is important for the ability of ABA penetrating into the lipid monolayer. Finally, a possible relevance of these results is discussed in terms of the action of ABA on guard cell membranes of plants. PMID- 8347671 TI - Spin-label studies on phosphatidylcholine-polar carotenoid membranes: effects of alkyl-chain length and unsaturation. AB - Spin-labeling methods were used to study the structure and dynamic properties of phosphatidylcholine (PC)-dihydroxycarotenoid membranes as a function of phospholipid alkyl chain length, alkyl chain saturation, temperature and mol fraction of carotenoids. (1) Dihydroxycarotenoids, zeaxanthin and violaxanthin increase order and decrease motional freedom of the lipid alkyl chains in fluid phase PC membranes. The effect of carotenoids decreases as the alkyl chain length of saturated PC increases. (2) The abrupt changes of spin-label motion observed at the main-phase transition of the saturated PC membranes are broadened and shifted to lower temperatures. At a carotenoid concentration of 10 mol%, they disappear for short-chain PC membranes (12-14 carbons), but are still observed for long-chain PC membranes (18-22 carbons). (3) In fluid-phase PC membranes possessing short alkyl chains (12-14 carbons), the activation energy of the rotational diffusion of 16-doxylstearic acid spin label (16-SASL) is significantly lower at a carotenoid concentration of 10 mol%. The difference decreases as the alkyl-chain length increases. (4) The presence of unsaturated alkyl chains greatly reduces the effects of carotenoids on the mobility of the polar headgroups as observed with tempocholine dipalmitoylphosphatidic acid ester and on the order of alkyl chains near the polar headgroup region as observed with 5-doxylstearic acid spin label (5-SASL). The effect of unsaturation is, however, moderate in the membrane center as shown with 16-SASL. Also, the effect of carotenoids on the order and motion of the rigid and highly anisotropic molecules dissolved in the PC membranes is significantly greater in saturated PC membranes. PMID- 8347672 TI - Diffusivity and structural polymorphism in some model stratum corneum lipid systems. AB - Mixtures of model stratum corneum lipids were prepared in water from cholesterol, six fatty acids and ceramides. The influence of composition on the polymorphism of these mixtures and also on the diffusivity of a model drug within them, Dlip, was determined. The former was obtained from X-ray diffraction and Fourier transform infrared spectrometry, and the latter from a diffusional release model. An L beta structure was formed for the composition approximating that of the extracellular lipids in intact human abdominal stratum corneum. Dlip was independent of water content in the range 20-40% w/w, with the bilayers showing one dimensional swelling without lateral expansion. Although removal of the ceramides did not result in a significant alteration in Dlip, crystalline cholesterol now appeared. The ceramides were, therefore, necessary for solubilization within the fatty acid bilayers of the large proportion of cholesterol present in the lipid fraction of intact SC. They were also responsible for a thermal L alpha-HII transition observed at approx. 68 degrees. At the concentration in which it exists in intact SC, cholesterol also had only a minimal effect on Dlip, but was necessary to suppress HII phase formation within the fatty acids and ensure an L beta structure. All lipid mixtures that had an L beta structure presented a diffusional barrier approx. 1 order of magnitude greater than that of an unstructured, isotropic lipid mixture. HII structures formed at cholesterol/fatty acid proportions less than approx 8:92 mol% and appeared more permeable than L beta ones. All the results indicate that the diffusional barrier within the model lipid mixtures is guaranteed essentially by the presence of an L beta phase. Although the ceramides and cholesterol exert no intrinsic influence on the magnitude of Dlip, their presence in necessary for the existence of an L beta phase at 33 degrees that is free of both crystalline cholesterol and HII character. PMID- 8347673 TI - Intersecting polymers in lipid bilayers: cliques, static order parameters and lateral diffusion. AB - We have modelled a macrolipid polymer composed of lipid molecules (monomers) embedded in a lipid bilayer or monolayer and polymerized via their polar groups. Because of fluctuations perpendicular to the plane of the bilayer, the polar region occupied by the polymer chain possesses sufficient space so that the polymer might exhibit 'self-intersection' if its conformational state is projected onto the plane of the bilayer/monolayer. We represent the plane of the bilayer/monolayer by a triangular lattice. Each site can be occupied by a monomer or be empty (and thus occupied by one of the unpolymerizable lipids which make up the bilayer/monolayer). A macrolipid is represented by a sequence of N monomers connected by N-1 bonds. Bonds may be either short (connecting nearest neighbour monomers) or long (between second neighbour monomers), in accord with the average properties of the spacers between the polymerized lipids. We have carried out computer simulation of this system using the Carmesin-Kremer bond stretching algorithm. Although no two monomers can occupy the same site, bonds may cross each other. We analyzed the dependence of and approximately N2vc and + approximately N2 sigma c, where Nsc and Nmc are the number of bond crossings in the same macrolipid ('self-crossing') or in two different macrolipids ('mutual-crossing'). For single macrolipids, we confirmed that vc = 3/4 and have found that sigma c approximately 0.52, which we consider supports that sigma c = 1/2. For the dense case with monomer concentration, c = 0.72, we found that vc = 1/2 and that sigma c approximately 0.52 supports that sigma c = 1/2. In the semi-dilute regime (c = 0.2) we found crossover behaviour, although sigma c = 1/2. The total number of bond crossings thus scale like N, independent of concentration. We studied the connectivity of the system by calculating the weight averaged cluster, or 'clique', size. Cliques are defined as being composed of all macrolipids which exhibit at least one crossing bond with one other member of the clique. We found that while the average clique contains about two macrolipids at low concentrations, the clique size approaches the maximum possible value at high concentrations if the macrolipids are sufficiently long. In the latter case a transition appears to occur as the macrolipid length increases. This transition occurs at length = 40 when c = 0.72. These observations should have experimental consequences for the viscoelastic properties of the system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8347675 TI - Stress causes alteration in attachment of rat hepatocytes to matrix protein substratum. AB - The effect of different types of stress on the attachment of rat hepatocytes to various matrix protein substrata, such as collagen IV, fibronectin and laminin, was investigated. Study of the kinetics of attachment of adult hepatocytes subjected to heat-shock at 45 degrees C for 30 min showed significantly lower attachment to collagen IV, fibronectin and laminin substrata when compared to untreated controls. The alteration in attachment was observed after heat treatment for 10 min and the extent of alteration appeared to increase with duration of the heat-treatment, as well as with increase in temperature. Foetal rat hepatocytes, which appeared to attach much more readily than adult rat hepatocytes to these substrata, particularly to laminin, also showed significantly lower attachment to all three substrata after heat-treatment at 45 degrees C for 30 min. This alteration in attachment appeared to be specific for matrix proteins as there was no significant effect on interaction of cells with non-matrix proteins, such as Con A and asialoglycoproteins. While the attachment of adult hepatocytes appeared to attain near control levels in about 4 h, the foetal cells recovered in about 2 h after heat-shock, indicating that the heat shock effect is reversible and the recovery is faster in foetal hepatocytes. Other stress-causing agents, such as heavy metals, also caused an alteration in attachment of hepatocytes to these matrix proteins. Attachment of adult and foetal hepatocytes to collagen substratum was reduced by 100-microM concentrations of heavy metals in the order Zn > Cd > La > As > Cu for adult cells and La > Zn > As/Cu > Cd for foetal cells. These heavy metals also caused significant reduction in attachment of adult hepatocytes to fibronectin and laminin, although the extent of inhibition was less than that for collagen substrata. However, these heavy metals did not significantly affect the attachment of foetal hepatocytes to laminin substratum indicating that the effect of heavy metals appeared to vary with the nature of the matrix protein substratum. On heat-shock, incorporation of [3H]leucine into cytoskeletal proteins such as cytokeratins CK8 and CK18 was reduced and significant amounts of two new proteins having an average molecular mass of 80 kDa and 90 kDa were found to be tightly associated with cytoskeletal proteins. PMID- 8347674 TI - Increased susceptibility of stored erythrocytes to anti-band 3 IgG autoantibody binding. AB - When human blood was stored in a citrate-phosphate-dextrose (CPD) solution at 4 degrees C, the susceptibility of the erythrocytes to binding of autologous IgG increased. The autologous IgG binding was partially inhibited by purified Band 3 glycoprotein and its oligosaccharides. The susceptibility of the erythrocytes to binding of 125I-labeled anti-band 3 IgG autoantibody similarly increased. The results indicate that the anti-band 3 binding sites composed of Band 3 oligosaccharides were generated on the cell surface. The rate of the increase in the susceptibility of the stored cells to the antibody binding was lowered when blood was stored in a CPD solution containing L-ascorbic acid or erythorbic acid, suggesting involvement of an oxidative mechanism in the generation of the binding sites. The cytoplasmic glutathione level of erythrocytes gradually decreased during the blood storage. Storing blood in a CPD solution containing glutathione monoethylester or glutathione monoisopropylester resulted in partial prevention of the decrease in cytoplasmic glutathione level and of the increase in the IgG binding ability of the cells. Similar preventive effect of glutathione monoethylester was observed in the binding of 125I-labeled anti-band 3 autoantibody to the stored erythrocytes. Thus, the increase in the susceptibility of the stored erythrocytes to anti-band 3 binding may be caused, at least partially, by an oxidative stress resulting in a decreased cytoplasmic glutathione level. PMID- 8347676 TI - An analysis of autologous glucocorticoid receptor protein regulation in AtT-20 cells also reveals differential specificity of the BuGR2 monoclonal antibody. AB - When the anti-glucocorticoid receptor monoclonal antibody (BuGR2) was initially incorporated either into a new immunoassay strategy or into a traditional sedimentation analysis technique, both methods failed to reveal any change in the cellular content or distribution of BuGR2-reactive antigen following glucocorticoid treatment of AtT-20 cells. Furthermore, the immunoassay also generated strong positive signals with cytosol and nuclear extracts from a receptor-negative cell line (E8.2) derived from L929 cells. However, when the BuGR2 antibody was incorporated into a combined immunoprecipitation/Western blot analysis of AtT-20 cell extracts, only the glucocorticoid receptor protein produced a signal on the Western blot, even though other proteins had been specifically immunoprecipitated by BuGR2 antibody and were clearly present on the Western blot membrane. Applying the latter approach to AtT-20 cells chronically treated with glucocorticoid, we observed not only that the receptor protein rapidly and persistently (1-96 h) accumulated in the nucleus, but also that its total cellular content was first depleted (24 h) and then was progressively replenished (48-96 h). From these studies in AtT-20 cells we conclude: (i), the BuGR2 antibody can exhibit differential immunospecificity dependent upon whether antigen mixtures are denatured or not; (ii), glucocorticoid receptor protein resided almost exclusively in the nucleus during four days of glucocorticoid treatment and (iii), the same treatment regimen resulted in total receptor protein levels being regulated in a biphasic pattern. Together, these results suggest that receptor regulation in AtT-20 cells is a complex event, and that, since steroid was constantly present during our experiments, other factors are involved in regulation of receptor levels. PMID- 8347677 TI - An analysis of the substrate specificity of insulin-stimulated protein kinase-1, a mammalian homologue of S6 kinase-II. AB - The specificity determinants for insulin-stimulated protein kinase-I (ISPK-1) have been investigated with synthetic peptides based on naturally-occurring protein phosphoacceptor sequences. Peptides (Arg-Arg-Xaa-Ser-Xaa) that fulfill the consensus sequence for cyclic-AMP-dependent protein kinase (PK-A) are also phosphorylated readily by ISPK-1. The phosphorylation efficiency is improved by increasing the number of N-terminal arginine residues and by moving the arginyl cluster one residue further away from the serine, the nonapeptide (Arg)4-Ala-Ala Ser-Val-Ala being the best substrate among all the short peptides tested (Km = 15 microM). Conversely, the substitution of either Thr for Ser or Lys for Arg is detrimental. Likewise, two flanking Pro residues and an Arg immediately N terminal to the Ser act as negative specificity determinants. While the specificity of ISPK-1 shows several similarities to that of PK-A, including an absolute requirement for basic residues on the N-terminal side of the target Ser, it differs in several other respects including (1), the detrimental effect of a Lys for Arg substitution which is still compatible with some phosphorylation by ISPK-1, but not PK-A; (2), the presence of C-terminal acidic residues which are tolerated very well by ISPK-1, but are detrimental to PK-A; (3), the effect of substituting Phe for Val in the peptide Arg-Arg-Ala-Ser-Val-Ala, which improves the efficiency of phosphorylation by PK-A (lowering the Km 4-fold), but has no effect on phosphorylation by ISPK-1. These differences in peptide substrate specificity may account in part for the different rates of phosphorylation of physiological substrates for ISPK-1 and PK-A, such as the G subunit of protein phosphatase-1. PMID- 8347678 TI - Identification of the product of the murine ST2 gene. AB - The murine ST2 gene is expressed in growth-stimulated BALB/c-3T3 cells. This gene encodes a protein that is similar to the extracellular portions of the interleukin-1 receptors (types 1 and 2). In this study, we prepared a polyclonal antibody against the recombinant ST2 protein produced in Escherichia coli. This antibody detected recombinant ST2 protein in the culture fluid of COS7 cells transfected with a mammalian expression vector (pEF-BOS) carrying ST2 cDNA. Using this antibody, we could detect the ST2 protein in the culture fluid of growth stimulated BALB/c-3T3 cells, and in the medium of continuously growing cells, but not in that of growth-arrested cells. ST2 proteins produced in COS7 cells and BALB/c-3T3 cells were N-glycosylated as predicted from nine putative N glycosylation sites in its deduced amino-acid sequence. PMID- 8347679 TI - A variety of calpain/calpastatin systems in mammalian erythrocytes. AB - Calpain and its endogenous inhibitor, calpastatin, were isolated from erythrocytes of various mammals and their properties were compared. It has been widely believed that mammalian erythrocytes contain only mu-calpain. However, rat and human erythrocytes were found to contain two species of calpain, identified as mu-calpain and m-calpain from their elution positions on DEAE-cellulose column chromatography and their Ca(2+)-requirements. Thus, it is apparent that rat and human erythrocytes contain not only mu-calpain, but m-calpain as well. On the other hand, rabbit erythrocytes contain only mu-calpain. Western blot analysis showed that human and rabbit erythrocytes contain predominantly 70-kDa calpastatin (erythrocyte-type), but unnegligible amounts of 110-kDa calpastatin (tissue-type) are also present. Rat erythrocytes were shown to contain a calpastatin with a molecular mass of approx. 100 kDa almost exclusively; this molecular mass was in perfect coincidence with the mass of the calpastatin in rat lung. These results strongly suggest that rat erythrocytes contain a tissue-type calpastatin. No essential change in the calpain/calpastatin system during maturation of rabbit reticulocytes into mature erythrocytes was observed. PMID- 8347680 TI - The functions of thrombospondin and its involvement in physiology and pathophysiology. AB - The thrombospondin family of molecules is expressed in many different tissues. Its expression is highly regulated by different hormones and cytokines and is developmentally controlled. It can bind to many different cell types, probably via an array of receptors which are similarly regulated. The level of thrombospondins in body fluids and their distribution in tissue change in correlation with various pathological states. It is linked to the growth of primary tumors and to metastasis, to development of the atherosclerotic plaque, to malaria infection and other diseases. The role(s) of thrombospondin(s) are by and large unknown, though specific interaction seem to affect particular cell functions. The wide-spread spatial and temporal regulation, multiple interactions and correlation with major diseases imply important roles in cell function and call for concerted effort to unravel the mystery. PMID- 8347681 TI - Amyloid formation by salmon calcitonin. AB - It is demonstrated using three independent methods that salmon calcitonin can form amyloid fibrils in vitro. Large aggregates are shown to exhibit a blue-green birefringence in cross polarised light after staining with congo red. Individual fibrils were observed using electron microscopy. These fibrils are approx. 50-60 A in diameter and up to 20,000 A in length and are similar in appearance to those observed in Alzheimer's disease. Finally, X-ray diffraction studies of the large aggregates reveal the cross-beta conformation characteristics of the monomers in the fibre. PMID- 8347682 TI - Redox metabolism of vitamin C in blood of normal and malaria-infected mice. AB - As oxidative mechanisms have been suggested to be part of the host immune reaction against malarial parasites, we investigated the redox metabolism of the antioxidant vitamin C in the blood of control and malaria-infected mice. At the peak of infection (day 6) with the malaria parasite P. vinckei, plasma levels of ascorbate (AH-) were 10.8 +/- 0.9 micrograms/ml compared to 5.7 +/- 0.7 micrograms/ml in control mice, though no significant change was observed in the plasma concentration of dehydroascorbate (DHA). The plasma redox ratio of vitamin C, [AH-]:[DHA], was 7.4 in control mice and 18.5 in infected mice on day 6 post inoculation. The increased AH- level in plasma of P. vinckei-infected mice was not due to differences in stabilities of either AH- or DHA in plasmas from control or P. vinckei-infected mice. DHA added to plasma was lost rapidly. In contrast, when added to whole blood. DHA was rapidly taken up and reduced to AH by blood cells from both normal mice and P. vinckei-infected mice. Most of the intracellular AH- derived from the exogenously added DHA was released into the plasma by blood cells from the infected but not normal mice. The observed release of AH- into the plasma by blood cells from infected mice was not caused by a plasma factor. Depletion of leukocytes from erythrocytes had no effect on the uptake and reduction of DHA by red blood cells, but the subsequent release of intracellular AH- occurred more rapidly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347684 TI - Pan-sulfation of bile salts markedly increases hydrophilicity and essentially abolishes self- and hetero-association with lecithin. AB - In chronic liver disease, partially and to a lesser extent completely (pan )sulfated common bile salts are synthesized, yet little information is available concerning their physical-chemical characteristics. We studied solution properties of pan-sulfated common free, taurine and glycine-conjugated bile salts, and the interactions of taurodeoxycholate di-sulfate (TDC-S) with lecithin. By reverse-phase HPLC, pan-sulfated glycine and taurine-conjugated bile salts were very hydrophilic, with hydrophobic indices 1.7 to 2.5 units lower than their non-sulfated congeners. In contrast to non-sulfated species, pan-sulfated free and glycine-conjugated bile salts produced simple potentiometric titration curves without precipitation of bile salt below the pK'A of the carboxylic acids. By quasi-elastic light scattering, critical micellar concentrations of TDC-S fell from 28 mM in 0.15 M NaCl to 3 mM in 4.0 M NaCl, a value slightly higher than that of TDC. TDC-S formed very small micelles (hydrodynamic radii approx. 11A) that, in contrast to TDC, did not grow with increases in bile salt (7-66 mM) or NaCl (0.15-2.0 M) concentrations. TDC-S formed mixed micelles with lecithin in 0.15 M NaCl, but with a micellar zone drastically reduced compared with that of the non-sulfated congener. However, in 4 M NaCl, the micellar zone of TDC-S expanded and approached that of the non-sulfated parent compound. Therefore, under physiological conditions, pan-sulfation of common bile salts should largely eliminate their capacity to form mixed micelles with membrane lipids. PMID- 8347683 TI - Tangier disease: isolation and characterization of LpA-I, LpA-II, LpA-I: A-II and LpA-IV particles from plasma. AB - Tangier disease (TD) is characterized by extremely low plasma levels of HDL, apoA I and apoA-II due to very rapid catabolism. However, the risk of premature coronary heart disease (CHD) is not markedly increased in TD. In order to gain insight into reverse cholesterol transport in TD, we isolated LpA-I, LpA-I:A-II, LpA-II and LpA-IV particles from fasting plasma of 5 TD patients. LpA-I composition was similar to control LpA-I, but TD LpA-I had more LCAT and CETP activity (respectively, 0.35 +/- 0.14 and 0.14 +/- 0.04 mumol of cholesterol esterified/h/micrograms of protein, and 7 +/- 2.5 and 1.4 +/- 0.3 mumol of cholesteryl ester transferred/h/micrograms of protein). In contrast, TD LpA-I:A II had abnormal composition, with a low molar ratio of apoA-I to apoA-II (0.2 1.33). In addition, LpA-I:A-II in TD contained a substantial amount of apoA-IV compared with control, making this particle an LpA-I:A-II:A-IV complex. LpA-I:A II from normal plasma do not promote cholesterol efflux from adipocytes cells, whereas TD LpA-I:A-II:A-IV complexes promoted cholesterol efflux from these cells. Moreover LpA-I:A-II:A-IV complexes have more LCAT and CETP activity than control (respectively 1.2 +/- 0.16 and 0.05 +/- 0.01 mumol of cholesterol esterified/h/micrograms of protein and, 41 +/- 3.7 and 1 +/- 0.4 mumol of cholesteryl ester transferred/h/micrograms of protein). The LpA-II particle in TD represented in fact an LpA-II:A-IV complex (75% mol apoA-II and 22% mol apoA IV).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347686 TI - Production of macrophage colony-stimulating factor (M-CSF) by human articular cartilage and chondrocytes. Modulation by interleukin-1 and tumor necrosis factor alpha. AB - A specific radioimmunoassay was employed to demonstrate that human articular cartilage and chondrocyte monolayers in organ and cell culture, respectively, produce macrophage colony-stimulating factor (M-CSF) in response to stimulation with interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF alpha) and TNF beta. Optimum doses were 10-100 U/ml for IL-1 (0.06-0.6 nM IL 1 alpha; 0.02-0.2 nM IL-1 beta) and 1-10 nM for TNF alpha. Low levels of M-CSF were observed in the supernatants of nonstimulated cultures while increased levels of M-CSF in response to IL-1 alpha and TNF alpha were detected following 2 h exposure to the cytokines. IL-1 alpha and TNF alpha did not show synergy for the production of M-CSF when both cytokines were added to cultures. Actinomycin D and cycloheximide inhibited both the basal and IL-1 alpha-induced production of M CSF, suggesting a requirement for de novo RNA and protein synthesis. Cytokine induced M-CSF production was also inhibited by the antiinflammatory corticosteroid, dexamethasone, but not by the cyclooxygenase inhibitor, indomethacin. The cytokines IL-4, IL-6, platelet-derived growth factor, leukemia inhibitory factor, transforming growth factor-beta and interferons -alpha and gamma, each had little or no effect on M-CSF levels, while basic fibroblast growth factor, lipopolysaccharide, and retinoic acid were each weak stimuli. We propose that chondrocyte M-CSF production in response to IL-1 and TNF alpha, and the concurrent destruction of cartilage by these cytokines, could provide a mechanism for the chronic nature of rheumatoid disease. PMID- 8347685 TI - Albumin Hawkes Bay; a low level variant caused by loss of a sulphydryl group at position 177. AB - A slow migrating minor albumin component, representing 5% of total circulating albumin, was detected by routine serum protein electrophoresis and immunofixation. After treatment with 5 mM dithiothreitol the abnormal component was found to migrate normally suggesting the attachment of some component to the free thiol at position 34. However, purification and analysis by SDS-PAGE showed that the abnormal component had a slightly lower apparent molecular weight than normal albumin. Limited tryptic cleavage indicated the abnormal site to be in the N-terminal third of the molecule. HPLC analysis of tryptic peptides from this domain showed the presence of a new peptide of sequence Ala-Ala-Phe-Leu- Leu-Pro Lys, indicating either a point mutation of 177 Cys-->Phe or the deletion of residues 166-177. DNA sequencing of PCR-amplified DNA confirmed the former Cys- >Phe substitution by indicating a point mutation of C to A at nucleotide position 5185. It appears that the aberrant electrophoretic mobility of the variant might be due to a gross conformational change associated with the formation of a new disulphide bond between Cys-168 and Cys-124. PMID- 8347687 TI - Inhibition of protein kinase C activity in mucolipidosis type-4: a model for a new pathogenetic mechanism in inborn errors of metabolism. AB - Inhibition of protein kinase C [PK-C] activity by sphingosine and its derivatives has been suggested to play a role in the pathogenesis of sphingolipidoses. In the present study, PK-C activity and PK-C-mediated phosphorylation of endogenous substrates were studied in skin fibroblasts from patients with mucolipidosis type 4 [ML-4], in which there is accumulation of the phospholipids phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine as well as gangliosides. Cytosolic PK-C activity in 5 ML-4 cell lines was comparable to that in control cells. PK-C activity in the particulate fraction of these cells was 84 +/- 14 pmol 32P/mg protein per min compared with 267 +/- 26 in control cells. Increasing the concentrations of the activating lipids in the reaction mixture did not enhance PK-C activity in ML-4 cells, suggesting a non-competitive inhibition of the kinase. Following partial purification of the enzyme from the particulate fraction PK-C activity increased to 288 +/- 14 and 339 +/- 12 pmol 32P/mg protein per min in ML-4 and control cells, respectively. The phosphorylation pattern of endogenous substrates in the particulate fraction of ML-4 cells differed from that in control cells both in the absence and in the presence of calcium and activating lipids. We suggest that PK-C may be involved in the pathogenesis of sphingolipidoses and that this may represent an example for a new type of pathogenetic mechanisms in inborn errors of metabolism. PMID- 8347688 TI - Substratum acidification and proteinase activation by murine B16F10 melanoma cultures. AB - Murine B16F10 melanoma cells, cultured within 0.7% agarose gels containing the fluorescent proteinase substrate acetamidofluorescein-BSA, catalyze the hydrolysis of the substrate in the region immediately surrounding the cell. Fluorescence ratio measurements on hydrolyzed substrate correlate with an average pH of 5.5 +/- 0.2 in the adjacent substratum region. Enzymatic activity within the gel is partially inhibited by leupeptin, pepstatin, phenylmethylsulfonyl fluoride. EDTA and by anti-human cathepsin B, suggesting potential roles for thiol-, aspartic- and metalloproteinases. The time-course of fluorescence intensity, correlated with substratum pH measurements, suggest that substrate hydrolysis is catalyzed by enzymes with pH optima of < 5.5. Invasion by these cells through thin barriers of reconstituted basement membrane gel (Matrigel) is totally blocked by the thiol proteinase inhibitor, leupeptin. It is suggested that secreted or cell-surface acid proteinase enzymes, activated by the cell mediated local hyperacidity, are involved in substrate hydrolysis and that these enzymes may be important in invasiveness by this cell-line. PMID- 8347689 TI - Identification of two new LDL-receptor mutations causing homozygous familial hypercholesterolemia in a South African of Indian origin. AB - South Africans of Indian origin have a high frequency of Familial Hypercholesterolemia (FH). Fibroblasts from a South African Indian FH homozygote, D, expressed about 30% of the normal number of LDL receptors. These receptors showed defective LDL binding. Sequence and haplotype analysis revealed that D had two different mutant LDL receptor alleles: FH Durban-1 is a point mutation [asp69(GAT) to tyr(TAT)] in ligand-binding repeat 2 and FH Durban-2 is a point mutation [glu119(GAG) to lys(AAG)] in ligand-binding repeat three of the LDL receptor. Single-strand conformational polymorphism analysis, which was used in the initial detection of these mutations, was also employed for subsequent population screening assays. These mutations were not detected in any of the South African Indian FH or hypercholesterolemic patients that were screened. PMID- 8347691 TI - Effects of monoclonal antibodies on alpha-staphylotoxin action against erythrocytes and model phospholipid membranes. AB - It was found that one of twenty tested monoclonal antibodies (MABs) existed which drastically enhanced ability of Staphylococcus aureus alpha-toxin (ST) to both lysis of human erythrocytes and increase of planar phospholipid bilayer conductance more than 10 and 1,000 times respectively. Other 19 MABs possessed only neutralized effect. The activation could only be observed if the activating MAB (AMAB) interacted with ST in solution but not in membrane. The one molecule of AMAB was able to activate approximately 2-4 molecules of ST. It was assumed that this activation was a result of the AMAB-induced transition of ST from a hydrophilic to an amphiphilic form. The activation could not be observed when the activity of AMAB/ST mixtures was tested on highly sensitive rabbit erythrocytes. All the tested MABs (including AMAB) were able to inhibit the ST-induced lysis of rabbit erythrocytes. The activating effects of AMAB on ST action in BLM and in human erythrocytes as well as their inhibiting influence on the ability of toxin to cause a lysis of rabbit erythrocytes indicate the presence of an ST-specific receptor on the membrane of rabbit erythrocytes. PMID- 8347690 TI - Pseudomonal elastase injection causes low vascular resistant shock in guinea pigs. AB - An intravenous injection of culture supernatants obtained from an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa exhibited immediate fall of mean arterial blood pressure from 63.8 +/- 1.62 to 35.6 +/- 2.31 mmHg (P < 0.001), increased heart rate from 249.6 +/- 3.86 to 272.6 +/- 2.18 beats/min (P < 0.05), and increased respiratory rate from 44.8 +/- 2.33 to 68.6 +/- 1.60/min (P < 0.01) within 5 min in the anesthetized guinea pigs. In contrast, culture supernatants obtained from an elastase non-producing strain (PA-103) did not cause the cardio-respiratory alterations, even though the same dose of endotoxin was contained in the supernatants. Intravenous or intracardiac injection of purified Pseudomonas aeruginosa elastase (1.2 mg/kg) but not endotoxin (up to 2.0 mg/kg) reproduced the immediate shock followed by death within 45 min in anesthetized or in conscious guinea pigs. Consistently, the shock-inducing ability of pseudomonal elastase was prevented by pretreatment with anti pseudomonal elastase rabbit F(ab')2 antibodies or with a synthetic inhibitor of pseudomonal elastase. Furthermore, intravenous injection of a non-lethal dose of pseudomonal elastase (0.8 mg/kg) immediately decreased peripheral vascular resistance when estimated from a change of perfusion pressure at hindquarter circulation from 74.0 +/- 1.00 to 52.6 +/- 1.76 mmHg (P < 0.05) in association with fall of arterial blood pressure and of cardiac output which was estimated from a change of regional aortic flow. The same low-resistant shock was also observed in rats. We speculate, therefore, that bacterial proteinases may play an important role in human septic shock. PMID- 8347692 TI - Outcome research: the gold standard for professional practice. PMID- 8347693 TI - Silent experts. PMID- 8347694 TI - Accuracy and response time comparisons of four skin temperature-monitoring devices. AB - Although technological improvements in skin surface temperature-measurement devices have progressed since they were first used clinically, the question of their accuracy and reliability for skin temperature monitoring still remains. The purpose of this study was to compare the accuracy and response time to temperature change for four temperature-monitoring devices: liquid crystal (Crystaline ST, Sharn, Inc, Tampa, Fla), two different thermistor sensors (RSP, Respiratory Support Products, Inc, Irvine, Calif, and SHER-I-TEMP, Sheridan Catheter Corp, Argyle, NY), and one thermocouple-based temperature sensor (Mon-a therm, Mallinckrodt, Inc, St. Louis, Mo). A temperature-controlled steel surface plate was used as the reference temperature source for test comparisons. The results showed that Crystaline ST (liquid crystal device) performed better in the accuracy and response time tests than the electronic thermistor and thermocouple temperature-sensor devices tested. Regression analysis of the reference temperature comparisons showed that although all four devices had high correlation coefficients Crystaline ST had the highest correlation (R = 0.99685). Also, the regression equation for Crystaline ST was closest to a perfect fit with reference temperatures, ie, slope = 1.00267 and intercept = 0.20333 (P = .0000). Crystaline ST responded consistently faster than the other devices for each change in temperature setting (5, 10, 15, and 20 degrees F). Crystaline ST responded within 3.5 to 4.4 seconds for every temperature gradient change tested. All three of the other sensor devices had increasingly longer response times as the temperature gradient increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347696 TI - Outcome assessment in education programs. AB - This article describes the move toward outcome assessment as a tool to measure student achievement and overall program effectiveness. Methods are presented by which on-site accreditation reviewers can determine if nurse anesthesia faculty perform effective assessments and utilize the results of their findings to plan for improvement. Emphasis is placed on methods by which data from multiple sources are collected and analyzed by the faculty to enhance student learning. PMID- 8347695 TI - A system of airway risk management in obstetric anesthesia. AB - This article describes an airway management system designed to reduce the incidence of maternal and neonatal mortality and morbidity during cesarean section. This system was developed from a comprehensive topical review of the literature and implemented in a midwestern community hospital. The key features of the system include a strategy of early assessment and recognition of patients at risk for difficult intubation, and the establishment of management protocols designed to reduce the maternal risk associated with failed intubation. PMID- 8347697 TI - Intraoperative awareness and recall during total hip arthroplasty. AB - A case of intraoperative recall and awareness in a patient with sickle cell disease who had received midazolam, 10 mg at induction of anesthesia, is reported. The patient was on opioids which may also have caused tolerance. Although the use of midazolam may have been judged to provide adequate amnesia, this was clearly not the case. Upon analysis of the reasons for recall, we predicted from a two-compartment model that the estimated blood level was 88 ng/mL-1; this level would have provided no amnesia. This case illustrates that recall can occur with the use of midazolam, especially if levels become subtherapeutic, and other measures should be taken to provide adequate anesthesia and amnesia. PMID- 8347698 TI - Patients who are susceptible to malignant hyperthermia. PMID- 8347699 TI - [Tuberculosis as health problem at the doorstep of the year 2000]. PMID- 8347700 TI - [Colonization by Streptococcus group B in full term pregnancy and newborns in a community in Venezuela]. AB - BACKGROUND: The aim of this study was to define the incidence of cervico-vaginal colonization by group B Streptococcus (SGB) in full term pregnancy as well as vertical and horizontal transmission in newborns attended in two public hospitals in Valencia, Venezuela. METHODS: An study cervico-vaginal exudates from 171 full term pregnant women was performed together with general obstetric survey. Oropharyngeal and nasal exudate studies in 118 newborns of the mothers studied were carried out during the first 12 hours after birth as was a neonatologic survey. RESULTS: The global percentage of maternal colonization by SGB were 32.7% while in the NB it was 45.8%. Among the NB colonized by SGB 73.2% were considered to have acquired the bacteria from the mother (vertical) with no significant differences in the data found in the two hospitals. The rate of horizontal colonization of the newborns was 42.3% in one hospital and only 8% in the second. CONCLUSIONS: There were no significant statistical differences between the rate of cervico-vaginal colonization in women attended in two public hospitals in Venezuela. No differences were observed in the rate of vertical colonization of newborns but to the contrary, that of the horizontal (nosocomial) colonization was of 42.3% and 8% in the Charity and University Hospitals, respectively. PMID- 8347701 TI - [Sexually transmitted diseases in a high risk subpopulation from the province of Soria]. AB - BACKGROUND: Women who practise prostitution constitute a high risk group for acquiring sexually transmitted diseases (STD). The aim of this study was to know the frequency of these processes among prostitutes in the province of Soria. METHODS: A descriptive transversal study including 86 women who voluntarily went to a Family Planning Center (FPC) in Soria was carried out in the period between October 1986 to December 1991. Patients were submitted to: investigation of T. vaginalis, N. gonorrhoeae, G. vaginalis, C. trachomatis, S. agalactiae and yeast infections. Complete clinical history was obtained from all including sociodemographic variables and those of risk of infection. RESULTS: Of the 86 women studied 12 (14%) had positive syphilis tests (treponemic and reaginic). In 12 (14%) N. gonorrhoeae was isolated. The search for C. trachomatis was positive in 16 (18.60%). In 19 (22.10%) T. vaginalis was directly observed. Twenty-three (26.74%) presented some type of positive serology to B virus. Five (5.81%) were HIV-1 seropositive. Candida spp. was isolated in 27 (31.39%) as was G. vaginalis and S. agalactiae in 21 (24.41%). Clinical examination did not show any macroscopic lesion suggesting venereal disease. CONCLUSIONS: Infection by Candida spp. and G. vaginalis were found to be the most frequent. The seroprevalence of HIV-1 in this series was the lowest in the country having a clear relation with the use of intravenous drugs (IVDA). Sexually transmitted diseases maintain a high prevalence in high risk groups such as prostitutes thus requiring energic prevention plans, overall in the group of young IVDA prostitutes. PMID- 8347702 TI - [Microbiological characteristics and spectrum of infections of 108 Streptococcus anginosus isolated]. AB - BACKGROUND: The aim of the present study was to assess the key microbiologic characteristics aid in the identification of Streptococcus anginosus in the laboratory and know the spectrum of clinical infections it produces. METHODS: From March 1991 to April 1992 all the isolated strains of clinical significant samples were collected. For identification the API 20 STREP (BioMerieux) system was used. The histories of the patients with infection by S. anginosus were retrospectively reviewed to collect clinical and microbiologic data of interest. RESULTS: The 108 strains of St. anginosus isolated were diminute colonies on sheep blood agar with CO2 enrichment. They had a characteristic smell, were beta hemolitic or non hemolitic and of the Lancefield group A, C, F, G or not groupable. All had invariable biochemical features in the API 20 STREP: produced acetone and alkaline phosphatase, hydrolized arginine, did not hydrolize hypurate nor did they ferment ribose. Streptococcus anginosus produced purulent infections of different localization: abdominal, head-neck, pleuro-pulmonary, muscle skeletal, skin and soft tissues and miscellaneous. Most of these infections were polymicrobial (81.5%). CONCLUSIONS: St. anginosus was easily identified in the laboratory by its morphologic characteristics and biochemical reaction in the API 20 STREP. It produced a wide variety of supurative infections, some being severe: cerebral, pulmonary, hepatic, empyema abscess. The identification of this microorganism at a species level should contribute to better recognition as a pathogen of occassionally severe supurative infections. PMID- 8347703 TI - [Evaluation of intestinal pathogenicity of Yersinia spp. strains isolated from human feces]. AB - BACKGROUND: Yersinia enterocolitica is a human pathogen which an acts on the intestine by basically enteroinvasive mechanism. Its virulence has been related with the presence of a plasmid of 40-50 MD which codes a series of properties. There are strains of Y. enterocolitica and of other species assimilated to the Y. enterocolitica group which lack the virulence plasmid. In these cases there is a problem in evaluating the pathogenic ability on the intestine of these bacterias when isolated in faeces. METHODS: A study of 30 Yersinia spp. strains including growth in a magnesium oxalate medium, Reg-Congo and agar (CR-MOX), sculine hydrolisis (Sc), pyrazinamidase activity (Pyz) and salicine fermentation (Sal) was performed. In addition, the presence of virulence plasmid (VP) was determined. RESULTS: Twenty-two strains identified as Y. enterocolitica presented the virulence pattern (CR-MOX+, Pyz-, Sal/Sc-) and 21 were VP+. Seven strains isolated were CR-MOX-, Pyz+, Sal/Sc+ and VP- being typed as Y. fredericksenii (6) and Y. kristensenii (1). The remaining strain was CR-MOX- and VP- but Pyz, Sal/Sc were also negative, being identified as Y. enterocolitica. CONCLUSIONS: By the tests referred the authors were able to identify and evaluate the pathogenicity of Yersinia spp. isolated in faeces. These techniques may be used in the microbiology laboratory as a method which aids to evaluate the diagnosis of intestinal infections caused by Yersinia spp. PMID- 8347704 TI - [Conjunctival ophthalmomyiasis caused by Oestrus ovis]. AB - BACKGROUND: Microbiologic diagnosis of conjunctival ophthalmomyiasis. MATERIAL AND METHODS: Material extracted from three patients' conjunctiva who complained of sudden presence of foreign body and were diagnosed as conjunctival ophthalmomyiasis has been studied. Patients were recruited over two months from the Emergency Department. Diagnosis was performed through observation using the light microscope. RESULTS: Oestrus ovis first-instance larvas were observed in all the samples studied. CONCLUSIONS: This observation of similar cases in a short period of time and the low frequency of diseased people who lived in a urban environment makes necessary to think in this agent as cause of ophthalmomyiasis in our area and therefore perform an adequate differential diagnosis. PMID- 8347705 TI - [Pathogenesis, epidemiology, and microbiologic diagnosis of infections caused by verotoxin-producing enterohemorrhagic Escherichia coli]. PMID- 8347706 TI - [Chronic polyarthritis]. PMID- 8347707 TI - [Septicemia caused by capnophilic microorganism]. PMID- 8347708 TI - [Bacillus cereus infection in orthopedic surgery]. PMID- 8347709 TI - [Septicemia caused by Streptococcus agalactiae in a previously healthy adult]. PMID- 8347710 TI - [Brucella abortus and myocardial involvement]. PMID- 8347712 TI - [Detection of respiratory syncytial virus antigen in respiratory secretions]. PMID- 8347711 TI - [Oligoarthritis and tenosynovitis caused by Haemophilus influenzae in a patient with myeloma]. PMID- 8347713 TI - [Disseminated histoplasmosis in AIDS patient]. PMID- 8347714 TI - [Periorbital abscess and paranasal sinusitis caused by Eikenella corrodens]. PMID- 8347717 TI - Genomes and informatics. PMID- 8347715 TI - [Diarrhea following antibiotic treatment, Clostridium difficile, and quinolones]. PMID- 8347716 TI - [Endocarditis caused by Capnocytophaga spputigena]. PMID- 8347718 TI - An overview of human-computer interaction. AB - This article presents an overview of the field of human-computer interaction. This branch of computer science concerns the design, implementation and analysis of interactive computer systems. We show that this field is multidisciplinary in essence, involving social scientists as well as computer scientists, experts of application domains, graphics designers, etc. Once the fundamental aspects of human-computer interaction are presented, we take a practical approach in order to introduce the methods, tools and techniques that are available today for the design and implementation of interactive computer systems. Finally, we present the main directions of research in this domain. PMID- 8347719 TI - The fundamentals of object-oriented database management systems. AB - The purpose of this document is to characterize the two technologies (database and object-oriented technologies) which constitute the foundation of object oriented database management systems. The O2 Object-Oriented DataBase Management System is then described as an example of this type of system. PMID- 8347720 TI - Artificial intelligence approach in analysis of DNA sequences. AB - We present an approach for designing a knowledge-based system, called Sequence Acquisition In Context (SAIC), that will be able to cooperate with a biologist in the analysis of DNA sequences. The main task of the system is the acquisition of the expert knowledge that the biologist uses for solving ambiguities from gel autoradiograms, with the aim of re-using it later for solving similar ambiguities. The various types of expert knowledge constitute what we call the contextual knowledge of the sequence analysis. Contextual knowledge deals with the unavoidable problems that are common in the study of the living material (eg noise on data, difficulties of observations). Indeed, the analysis of DNA sequences from autoradiograms belongs to an emerging and promising area of investigation, namely reasoning with images. The SAIC project is developed in a theoretical framework that is shared with other applications. Not all tasks have the same importance in each application. We use this observation for designing an intelligent assistant system with three applications. In the SAIC project, we focus on knowledge acquisition, human-computer interaction and explanation. The project will benefit research in the two other applications. We also discuss our SAIC project in the context of large international projects that aim to re-use and share knowledge in a repository. PMID- 8347721 TI - An automatic approach for DNA sequencing. AB - Automation is perfectly suited to DNA sequencing, which requires many repetitive steps and the handling of many samples. It increases not only processing capability but also accuracy and reproducibility. We present an approach to automation of DNA sequencing that was developed at the level of a research laboratory, and describe several improvements to DNA sequencing methodology. PMID- 8347722 TI - Learning and alignment methods applied to protein structure prediction. AB - Learning techniques are able to extract structural knowledge specific to a selected set of proteins. We describe two algorithms that optimize scores expressing the propensity of a polypeptide sequence to adopt a local fold. The first algorithm generates secondary structure prediction rules based on a dictionary of geometrical patterns frequently found in the learning database. The second algorithm leads to scores that indicate the fit between an amino acid and a given local structural environment. Dynamic programming is then used to align structural information profiles by modifying the local mutation cost with the above learned functions. The main features of the system are exemplified on the structural prediction of the N-terminal domain of the CD4 antigen. Then the usefulness of additional 3-D information in the alignment is benchmarked on eight pairs of weakly homologous proteins. PMID- 8347723 TI - Inductive learning and biological sequence analysis. The PLAGE program. AB - Inductive learning, also called 'learning from examples', is a subfield of artificial intelligence. Inductive learning methods are able to deal with 'structural descriptions'. These portray objects as composite structures consisting of various components. The use of structural descriptions to represent biological objects is appealing. For instance, they have been used by Rawlings et al [1] for symbolically and comprehensively representing the folding of proteins. This paper shows how inductive learning techniques may be used for extracting information from biological objects. We briefly describe some general techniques for describing objects in a structural way and for learning from these descriptions. We present details of a program that we developed, PLAGE, and show the application of this program for a study on signal peptides, which was done in collaboration with A Danchin [2,3]. Finally, we survey some other approaches and applications of inductive learning to molecular biology. PMID- 8347724 TI - Local predictability in biological sequences, algorithm and applications. AB - The goal of this paper is to propose an algorithm based on the k nearest neighbours to compute a local predictability measure in biological sequences. Some ideas about the usefulness of this measure are discussed on the basis of preliminary experimentations. PMID- 8347726 TI - Identification and simulation of new non-random statistical properties common to different eukaryotic gene subpopulations. AB - The nucleotide distribution in protein coding genes, introns and transfer RNA genes of eukaryotic subpopulations (primates, rodent and mammals) is studied by autocorrelation functions. The autocorrelation function analysing the occurrence probability of the i-motif YRY(N)iYRY (YRY-function) in protein coding genes and transfer RNA genes of these three eukaryotic subpopulations retrieves the preferential occurrence of YRY(N)6YRY (R = purine = adenine or guanine, Y = pyrimidine = cytosine or thymine, N = R or Y). The autocorrelation functions analysing the occurrence probability of the i-motifs RRR(N)iRRR (RRR-function) and YYY(N)iYYY (YYY-function) identify new non-random genetic statistical properties in these three eukaryotic subpopulations, mainly: i) in their protein coding genes: local maxima for i identical to 6 [12] (peaks for i = 6, 18, 30, 42) with the RRR-function and local maxima for i identical to 8 [10] (peaks for i = 8, 18, 28) with the YYY-function; and ii) in their introns: local maxima for i identical to 3 [6] (peaks for i = 3, 9, 15) and a short linear decrease followed by a large exponential decrease both with the RRR- and YYY-functions. The non random properties identified in eukaryotic intron subpopulations are modelised with a process of random insertions and deletions of nucleotides simulating the RNA editing. PMID- 8347725 TI - Likelihood linkage analysis (LLA) classification method: an example treated by hand. AB - This paper describes a very general method of data analysis using a hierarchical classification. The data can be provided by observation, experiment or knowledge; their nature can be numerical, qualitative or logical. First, the classical view of the context of data representation, in which the algorithm of hierarchical ascendant construction of the classification tree is set, is treated in a synthetic manner. The main notion in our method is one of 'similarity'. This must be elaborated in the best way, taking into account the mathematical nature of the objects to be compared. Here we adopt a set of theoretical and combinatorial representation of the descriptive attributes, which are interpreted in terms of relations. Then we introduce a probability scale for similarity measurement by using a likelihood concept. The largest part of the paper concerns an illustrating example, moderately sized, detailing very minutely the different steps and the different calculations assumed by the method. The data structure handled with this example is the simplest possible. Then, general aspects and methodological extensions are evoked. We end by indicating the interest of the described approach in future works, in which we are involved, concerning typological organization of genetic sequences. We emphasize the 'explanation' aspect of the obtained results, with respect to a given description. For this purpose, classifications (on the object set and on the attribute set) on the one hand and machine learning techniques on the other, intervene efficiently. PMID- 8347727 TI - Analytical approaches to genomic evolution. AB - We model the non-local mechanisms of genomic evolution and propose methods for studying the evolutionary divergence of species based on these models. Mechanisms include the movement of segments of genomes within a single chromosome (transpositions), the reciprocal translocation of segments between two chromosomes, and the inversion of segments. Each of these is studied in the context of a different type of genomic data. We introduce the theory of phylogenetic invariants for evolutionary inference based on very long macromolecular sequences. PMID- 8347728 TI - ColiGene: object-centered representation for the study of E coli gene expressivity by sequence analysis. AB - ColiGene is an object-centered knowledge base for the study of gene expressivity in Escherichia coli by DNA sequence analysis. This system was developed with the knowledge base management system SHIRKA. Objects represented in ColiGene are biological structures such as genes or regulatory signals. They are organized in a hierarchical structure of classes, subclasses and instances. Navigation through the knowledge base and the building of queries are made using a graphical interface. The base is coupled with the data base ACNUC which structures a specialized collection of sequences: EcoSeq. Several tools are also associated to ColiGene, either for sequence analysis or for a more general purpose. Some biological results have been obtained using ColiGene which are summarized here. PMID- 8347729 TI - Interferon in chronic myeloid leukemia. A workshop report. AB - The therapeutic efficacy of interferon-alpha (IFN-alpha) in the treatment of chronic myeloid leukemia is currently being tested in a number of institutional, interinstitutional, and international trials. There is no doubt that responses are achieved in many patients, and in a small subset complete eradication of clonogenic cells may be possible. However, it has not yet been shown that overall survival of patients treated with IFN-alpha is better than that of those treated with conventional cytoreductive drugs. There are still controversial opinions on problems such as dosages and duration of treatment, combination with cytostatic agents, definition of responses, and relevance of cytogenic and molecular data. An international workshop discussed the data on interferon therapy and attempted to define the role of interferon today in the management of chronic myeloid leukemia. PMID- 8347730 TI - Primary thrombocythemia: diagnosis, clinical manifestations and management. PMID- 8347731 TI - Ubenimex in the treatment of acute nonlymphocytic leukemia in adults. AB - A multi-institutional randomized study for the evaluation of ubenimex (Bestatin) in the treatment of adult acute nonlymphocytic leukemia was performed. One hundred and ninety-five patients were registered from February 1988 to December 1990. Patients who had reached complete remission by one or two courses of remission induction chemotherapy were divided into the ubenimex group or the control group by randomization. Patients of the ubenimex group started to receive 30 mg ubenimex orally once a day when maintenance therapy began and continued as long as possible. Remission duration and survival were analyzed based on the data as of August 31, 1991. Remission duration of the ubenimex group was superior to that of the control group (generalized Wilcoxon test: p = 0.0338). Fifty percent remission duration was 508 days in the ubenimex group and 386 days in the control group. There has been no statistical difference in survival between the two groups as yet. PMID- 8347732 TI - IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-P). AB - Experimental animal and human in vivo studies have previously demonstrated the impact of exogenous administration of various cytokines on frequencies of circulating myeloid and LAK precursor cells. For the first time we investigated whether exogenous cytokines, in the absence of antigenic challenge, may also influence frequencies of circulating antigen-specific cytotoxic T-lymphocyte precursor cells. We further asked whether triggering of autoimmune pathways as has been reported for several cytokines can be confirmed on the cellular level by demonstration of induction of autoreactive CTL-p. Limiting dilution analysis was used to determine alloreactive CTL-p frequencies in 31 patients with nonhematologic diseases before and after short-term systemic treatment with either rIL-2 (4.8 x 10(6) IU/m2 bid), rIL-3 (2.5, 5.0 or 10.0 micrograms/kg qd), rGM-CSF (5 micrograms/kg qd), rIFN-gamma (200 or 400 micrograms qd), or IFN-alpha (3 or 5 x 10(6) IU qod). Simultaneously, autoreactive CTL-p frequencies were determined by split-well analysis in 25 of these patients. We found that rIL-2 significantly expands the circulating precursor pool of alloreactive CTL (p < 0.05). rIL-3 affected CTL-p frequencies in a dose-dependent fashion. Low and intermediate doses of rIL-3 did not exhibit significant effects, whereas 10 micrograms/kg rIL-3 led to expansion of alloreactive CTL-p in the same order of magnitude as did rIL-2. This effect was statistically significant when compared with rGM-CSF (p < 0.02), which apparently had no influence on alloreactive CTL-p frequencies. In contrast to rIL-2 and rIL-3, exogenous rIFN-gamma markedly reduced the circulating precursor pool of CTL. This again was statistically significant compared with rIFN-alpha (p < 0.03), which, like rGM-CSF, did not exhibit any effects on the level of alloreactive CTL-p. Frequencies of autoreactive CTL-p were invariably below the limit of detection in our system (< 1/300,000). In conclusion, these data demonstrate that (a) short-term systemic administration of rIL-2, rIL-3, and rIFN-gamma differently affects the clone size of circulating precursors of alloreactive CTL in man, while rGM-CSF and rIFN alpha do not exhibit measurable effects, and (b) none of the cytokines administered is capable of uncovering detectable frequencies of autoreactive CTL p. PMID- 8347733 TI - Comparison of 5 vs 10 micrograms/kg per day of GM-CSF following dose-intensified chemotherapy with cisplatin, etoposide, and ifosfamide in patients with advanced testicular cancer. AB - Despite the increasing use of granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of chemotherapy-induced neutropenia, few studies have focused on the activity and toxicity of the different clinically used dosages of GM-CSF. Forty-four patients with "poor-risk" (advanced disease, according to the Indiana University classification) testicular cancer were treated with a dose intensified chemotherapy regimen of cisplatin (30 mg/m2), etoposide (200 mg/m2), and ifosfamide (1.6 g/m2), given on days 1-5 for a total of four cycles at planned intervals of 21 days. Patients (pts) received GM-CSF, either 10 (22 pts; 70 cycles evaluable) or 5 micrograms/kg body wt. daily s.c. (22 pts; 72 cycles evaluable), starting the first day after chemotherapy for 10 consecutive days. Overall, 34 patients (78%) achieved a favorable response (CR or PR with negative tumor markers), six patients (14%) failed this chemotherapy regimen, and four patients (9%) died of therapy-related complications. The durations of both neutropenia and thrombocytopenia increased with the number of treatment cycles given. The duration of granulocytopenia after the fourth PEI cycle was significantly shorter for patients receiving 10 micrograms/kg than for those with 5 micrograms/kg per day of GM-CSF (9 vs 13 days; p < 0.05). The median duration of thrombocytopenia < 20,000/microliters after the fourth cycle of PEI was also significantly reduced in favor of patients receiving 10 micrograms/kg of GM-CSF (4 vs 9 days; p < 0.02). However, there were no differences in the frequency of severe infections or in the achieved dose intensity. Five patients (11%) discontinued GM-CSF due to side effects (three anaphylactoid-type reactions, one myalgia and fever, one cutaneous toxicity). No difference in the frequency of side effects was seen between patients receiving 5 and those receiving 10 micrograms/kg per day of GM-CSF. The dose of 5 micrograms/kg per day of GM-CSF may be sufficient to ameliorate neutropenia following standard-dose chemotherapy, while higher dosages of GM-CSF may be advantageous in patients receiving repetitive cycles of dose-intensified chemotherapy. PMID- 8347734 TI - Biotin labeling as an alternative nonradioactive approach to determination of red cell survival. AB - Biotin labeling of red cells was studied using different approaches to see if biotinylation is a useful label for determination of erythrocyte survival. Mouse red cells were labeled with biotin, either in vivo by injection or in vitro. In vivo labeled red cells were followed up in some mice without transfusing the labeled erythrocytes. Furthermore, in vivo labeled as well as in vitro labeled red cells were transfused into syngeneic mice. The biotin label allows an easy discrimination between labeled and unlabeled red cells during FACS analysis, and it is relatively stable for at least 50 days. All the three different approaches give similar results. Mean red cell life spans of in vivo or in vitro labeled red cells either transfused or followed up in vivo were between 44 and 52 days (T50 mean 23.9 days) when red cell destruction was assumed to be only a result of senescence. Mean red cell life spans were between 8 and 18 days (T50 mean 9.5 days) when a random destruction independent of red cell age was suggested. All the survival slopes are neither simple linear functions of time nor logarithmic functions, but they show an overlay of linear function by a logarithmic function where the components of both are unknown. PMID- 8347735 TI - Combined ankyrin and spectrin deficiency in hereditary spherocytosis. AB - Hereditary spherocytosis is characterized by a reduced spectrin content of the erythrocytes. However, the underlying primary defect remains unclear in the majority of cases. Genetic studies have revealed a linkage to the gene for ankyrin in some families. By means of ELISA we measured the ankyrin, spectrin, and band-3 contents in erythrocytes of 45 patients with typical spherocytosis. They were classified as having mild or moderate spherocytosis, according to clinical severity. Sixteen patients with mild spherocytosis showed slight reductions of ankyrin and spectrin contents. In contrast, 29 patients with moderate spherocytosis exhibited a clear reduction of both ankyrin and spectrin to about 60% of normal. Band 3 and lipid phosphorus, as measures for membrane surface area, were only slightly reduced to 85%. Our results, together with the molecular genetic data indicating the linkage between spherocytosis and the gene for ankyrin, suggest an ankyrin defect or deficiency as the primary lesion in most cases of spherocytosis. PMID- 8347737 TI - Pooling epidemiologic studies. PMID- 8347736 TI - Does depression cause heart disease? PMID- 8347738 TI - Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults. AB - Major depression has been associated with mortality from ischemic heart disease (IHD). In addition, a symptom of depression--hopelessness--has been suggested as a determinant of health status. We studied the relation of both depressed affect and hopelessness to IHD incidence using data from a cohort of 2,832 U.S. adults age 45-77 years who participated in the National Health Examination Follow-up Study (mean follow-up = 12.4 years) and had no history of IHD or serious illness at baseline. We used the depression subscale of the General Well-Being Schedule to define depressed affect and a single item from the scale to define hopelessness. At baseline, 11.1% of the cohort had depressed affect; 10.8% reported moderate hopelessness, and 2.9% reported severe hopelessness. Depressed affect and hopelessness were more common among women, blacks, and persons who were less educated, unmarried, smokers, or physically inactive. There were 189 cases of fatal IHD during the follow-up period. After we adjusted for demographic and risk factors, depressed affect was related to fatal IHD [relative risk = 1.5; 95% confidence interval (CI) = 1.0-2.3]; the relative risks of fatal IHD for moderate and severe levels of hopelessness were 1.6 (95% CI = 1.0-2.5) and 2.1 (95% CI = 1.1-3.9), respectively. Depressed affect and hopelessness were also associated with an increased risk of nonfatal IHD. These data indicate that depressed affect and hopelessness may play a causal role in the occurrence of both fatal and nonfatal IHD. PMID- 8347739 TI - Methods for pooled analyses of epidemiologic studies. AB - This paper presents a systematic methodology for the pooling and analysis of previously conducted epidemiologic studies. It discusses the methodologic issues to consider and the procedures to follow when conducting a pooled analysis of individual subject level data. I review random and fixed effects models to estimate pooled risks and the methods to examine whether heterogeneity in study specific effect estimates exists. Analytic strategies presented here can be used to assess sources of heterogeneity, particularly those originating from different study designs and methods. I describe methods for incorporating a qualitative assessment of the study design and data collection methods into the quantitative estimation of the overall effect. Finally, I make recommendations for future pooled analyses of epidemiologic studies. PMID- 8347740 TI - Gravidity, blood pressure, and hypertension among white women in the Second National Health and Nutrition Examination Survey. AB - Gravidity and parity have been hypothesized as possible protective factors for hypertension in women, but results of previous studies have been conflicting; none of three U.S. studies has clearly demonstrated this relation. We studied the association of number of pregnancies to blood pressure and hypertension in a cross-sectional study of 4,626 white women, ages 20-74 years, examined in the Second National Health and Nutrition Examination Survey. In univariate analyses, neither mean systolic blood pressure, mean diastolic blood pressure, nor prevalence of hypertension varied systematically with the number of pregnancies. In multivariate analyses that included age, body size, smoking, oral contraceptive use, education, poverty status, and alcohol use, systolic blood pressure declined modestly with greater gravidity. The association of gravidity with systolic blood pressure was stronger for younger premenopausal women. The odds of hypertension also declined with each additional pregnancy as compared with no pregnancies: there was an odds ratio of 0.90 (95% confidence interval = 0.81-0.99) for premenopausal women and an odds ratio of 0.95 (95% confidence interval = 0.92-0.98) for postmenopausal women. These findings indicate a slight negative relation of number of pregnancies to both blood pressure and hypertension. PMID- 8347741 TI - Interpreting model coefficients when the true model form is unknown. AB - In this paper, we critically examine mathematical modeling. We outline the major assumptions required by modeling methods used in epidemiology and discuss in detail one fundamental assumption that is usually violated in epidemiologic studies: the assumption that the structural model form is correctly specified. We apply concepts from the econometrics literature to examine how epidemiologic inference may be affected when the structural model form is incorrectly specified. Because the structural model is almost always misspecified in practice, tests and confidence intervals for model coefficients do not refer to "true population parameters" in the ordinary sense. Rather, these statistics concern parameters that depend on features of study design, as well as the effects under study. In cohort studies analyzed with multiplicative rate models, model parameters are interpretable as approximations to log standardized rate ratios; unfortunately, such interpretations are not as accurate for other models and designs. We therefore conclude that model coefficients can serve as reasonable effect summaries in some, but not all, situations. PMID- 8347742 TI - How well do prediction equations predict? Using receiver operating characteristic curves and accuracy curves to compare validity and generalizability. AB - Although morbidity and mortality prediction equations are widely used in planning, clinical practice, and health risk appraisal, their validity and generalizability have been tested only in a limited way. Previous attempts lacked an absolute standard of performance and looked only at the equations' ability to predict who would become ill (sensitivity), not the equally important ability to predict who would remain healthy (specificity). We compared six all-cause mortality prediction equations using receiver operating characteristic curves and accuracy curves, which overcome the limitations of earlier methods and provide a concise visual representation of the results. We used equations from five prospective studies conducted in the United States (Tecumseh at 8 and 12 years of follow-up, Framingham, Chicago Gas, Chicago Western Electric, and Albany), each of which included cholesterol, smoking, and blood pressure as independent variables, to predict 12-year mortality in Tecumseh males age 40-54 years. Previous studies suggested that these equations predict equally well. Our analysis found that, although all predict better than chance, Albany, Chicago Western Electric, and Tecumseh at 8 years underestimate mortality. Receiver operating characteristic and accuracy curves are a promising technique for assessment of prediction equations. PMID- 8347743 TI - Use of two data sources to estimate odds ratios in case-control studies. AB - Information bias is among the most serious and common problems in epidemiology. Approaches have been developed to reduce information bias by correcting for known amounts of misclassification. Unfortunately, in most studies, the extent of exposure misclassification cannot be easily estimated. We discuss the application to case-control studies of an approach originally proposed by Hui and Walter in 1980 to estimate the sensitivity and specificity of two independent classification schemes (Hui SL, Walter SD. Biometrics 1980;36:167-171). In this paper, we propose using the EM algorithm to provide a simple numeric technique for implementing their method that seems to converge for most real-world data. Our approach allows inclusion of a measure of non-independence of the two classification schemes, and we assess the influence of non-independence on the odds ratio. Finally, we provide a simple variance estimate for the odds ratio based on the delta method and maximum likelihood theory. We exemplify our results and method with data from a case-control study of sudden infant death syndrome in which data on some variables were obtained from both maternal interviews and medical records. PMID- 8347744 TI - Confounding by time since hire in internal comparisons of cumulative exposure in occupational cohort studies. AB - We use a simple, empirical model to describe the healthy worker effect mortality pattern. Under this simple model, internal comparisons of risk with increasing cumulative exposure will tend to be biased away from the null because of the healthy worker effect. We illustrate the potential magnitude of the bias in a simple situation and show that controlling for time since hire, by means of standard epidemiologic methods, eliminates the bias. Time since hire also is a concern of occupational epidemiologists because of the issue of induction time; sufficient time may not have elapsed among recently hired workers for an exposure to manifest its effect on disease occurrence. Provision for an adequate induction period can be addressed, like the concern raised in this paper, by restricting the analysis to workers first employed many years before the start of the follow up period. PMID- 8347745 TI - Physical activity and risk of endometrial cancer. AB - In a population-based case-control study of endometrial cancer, we interviewed 268 cases and an equal number of matched controls regarding physical activity at work and outside of work. We also obtained self-ratings of overall physical activity levels. The results showed that nonretired women holding sedentary jobs or those reporting sedentary life-styles were at somewhat increased risk of endometrial cancer. The associations remained unchanged after adjustment for caloric intake and body mass index. Although an effect of physical inactivity on endometrial cancer risk is biologically plausible, our results show some inconsistencies, such as a lack of elevation in risk among women who were physically inactive outside of work. PMID- 8347746 TI - The accuracy of parental reports of their children's intake of fruits and vegetables: validation of a food frequency questionnaire with serum levels of carotenoids and vitamins C, A, and E. AB - It has been recommended that U.S. children increase their dietary intake of fruits and vegetables. Measuring diets of children to support and evaluate nutritional interventions can be a difficult task, however. We administered to 97 parents of children age 6-10 years a food frequency questionnaire on their children's usual dietary intake over the previous 3 months. We then compared these reports by parents of their children's intakes of fruits and vegetables, and the derived estimates of intake of carotenoids and vitamins C, A, and E, with the children's serum levels of carotenoids and vitamins C, A, and E. The dietary reports of intakes of 35 fruits and vegetables showed Spearman rank-order correlations of 0.30 with serum carotenoids and 0.34 with serum vitamin C. Children in the highest quartile for intake of fruits and vegetables according to their parents' food frequency reports had 35% higher carotene levels and 31% higher vitamin C levels in their serum than did children in the lowest quartile for intake of fruits and vegetables. We conclude that parental reports of young children's diets using food frequency methods are accurate enough to be useful in nutritional screening and dietary surveillance of fruit and vegetable intake. PMID- 8347747 TI - The reproducibility and validity of a self-administered semiquantitative food frequency questionnaire in subjects from South Dakota and Wyoming. AB - Most validation studies of food frequency questionnaires have been done in populations capable of reporting their diet with unusual accuracy. In this study of ranchers and subjects selected at random, we compared nutrient intakes as assessed with multiple diet records with those assessed with a self-administered food frequency questionnaire (the Harvard-Willett instrument with 116 food items). One hundred thirty-eight subjects from South Dakota and Wyoming, 64 males and 74 females, completed at least one food frequency questionnaire and multiple 1-day diet records (mean = 5 days) during a 6-month to 1-year period. Of invited subjects, 88% participated; 59% of participants had a high school education or less. For 22 dietary nutrients (excluding supplements) and alcohol, the median crude correlation between intakes based on diet records and the food frequency questionnaire completed before the diet records was 0.42; after adjustment for energy, age, and sex, and after correction for attenuation in the correlation coefficients due to error from a limited number of diet records, the median correlation was 0.52. Correlations for men and women were similar. The validity of the food frequency questionnaire in this population was similar to that reported previously and supports the use of self-administered food frequency questionnaires in studies of general populations. PMID- 8347748 TI - A meta-analysis of coffee, myocardial infarction, and coronary death. AB - This paper presents a meta-analysis of 22 studies of coffee use and myocardial infarction or coronary death. In the eight case-control studies, a fairly homogeneous increased risk was found among coffee users (geometric mean rate ratio of 1.42 for 5 cups per day vs none, with 95% confidence limits of 1.30, 1.55, homogeneity P-value of 0.89). The 14 cohort studies tended to exhibit lower but very heterogeneous rate ratios, with a trend toward larger rate ratios in studies with longer follow-up periods and later publication dates (geometric mean rate ratio of 0.92 for the five cohort studies published up to 1981, 1.27 for the nine cohort studies published in 1986 or later; overall homogeneity P-value of 0.0008). The evidence thus remains ambiguous regarding both the existence and size of a coffee effect, and although a rate ratio of over 1.5 for 5 cups per day appears unlikely, stronger effects for 10-cup-per-day drinkers cannot be ruled out. PMID- 8347749 TI - Comparison of early and late respondents to a postal health survey questionnaire. AB - We mailed a health survey to the 18,408 residents of a California retirement community and compared the 11,550 respondents on a number of characteristics by time of response. Early respondents were more likely to be the "worried well," that is, healthy individuals who see their doctor regularly, receive disease detection screening, and follow healthful life-style practices. Late respondents tended to answer questions regarding their mental function and emotional status more negatively. Early and late respondents did not differ in the rates of death or hospitalization during the first 5 years of the study; nonrespondents had a higher incidence of hospitalization than respondents in year 1 and higher death rates in the first 3 years, but not thereafter. PMID- 8347750 TI - Telephone answering machines: the influence of leaving messages on telephone interviewing response rates. AB - We studied women 45-54 years of age from two communities who failed to return a mailed survey in an experiment to assess the impact on interviewing response rates of leaving messages on telephone answering machines at the time of telephone follow-up. There were 88 and 103 subjects assigned to the "message" and "no message" groups, respectively. After adjustment for age, interviewer, and community, leaving messages increased the rate of reaching a household by about 15% and improved the overall interviewing response rate by about 15% as well. This improvement was more apparent in women from the higher socioeconomic status community. PMID- 8347751 TI - Combined estrogen and progesterone use and endometrial cancer. PMID- 8347752 TI - Measures of effect based on the sufficient causes model. PMID- 8347753 TI - Measures of effect based on the sufficient causes model. PMID- 8347754 TI - A moment in time. PMID- 8347755 TI - The history and current status of paramedical support for the ostomy patient. PMID- 8347756 TI - Alcohol and other drug abuse in elders. AB - With the growing population of older persons, ET nurses can expect an increasing number of elderly clients in their practice settings. Elderly persons are not immune to alcohol and other drug abuse. Detection of substance abuse in this population is complex and often missed. The purposes of this article are as follows: (1) examine barriers that may prevent nurses from addressing substance abuse among the elderly population; (2) suggest risks for psychoactive substance abuse in this population; (3) identify warning signs that should alert nurses to the problem; and (4) outline treatment options for substance-abusing clients. PMID- 8347757 TI - Interface pressure measurements of support surfaces with subjects in the supine and 45-degree Fowler positions. AB - In the past 20 years there has been a dramatic increase in different types of support surfaces to reduce the incidence of pressure ulcers. The purpose of this study was to determine the effect of static air overlays (Sof-Care and Tendercloud), replacement mattresses (Dermarest and Therarest), and a standard hospital mattress on tissue interface pressures in healthy subjects. A convenience sample of 25 subjects had tissue interface measurements obtained under the sacrum and heel bony prominences on the five support surfaces in the supine and 45-degree Fowler's positions. A repeated measures analysis of variance (p < 0.05) indicated that the Dermarest, Therarest, Sof-Care, and Tendercloud support surfaces reduced pressure significantly under the sacral bony prominence compared with the standard hospital mattress. Heel interface pressure measurements were significantly higher than sacral interface pressure measurements. There was no significant difference between supine and 45-degree Fowler's positions with respect to tissue interface pressures. PMID- 8347758 TI - Use of computer technology in ET nursing. AB - ET nurses frequently share ideas and products that suddenly make our job and patient care much easier. But little has been discussed in the Journal of ET Nursing to shed light on the speed, accuracy, efficiency, improved communication, and long-term cost-effectiveness that computer technology can bring to our chosen specialty. This article identifies use of computer technology in practice, education, and research. Such applications will bring about a change in present practice methods. Everett Roger's change theory can assist in the change process. Our mission is to provide state-of-the-art health care for individuals with wounds, ostomies, and incontinence. Computer technology can assist in that mission by increasing productivity and effectiveness of the ET nurse. PMID- 8347759 TI - Purple ulcers. PMID- 8347760 TI - Air support therapy. PMID- 8347761 TI - Braden Scale and clinical judgment. PMID- 8347763 TI - Twenty-five years in colon and rectal surgery: changes and progressions. PMID- 8347762 TI - Ileostomy complications. PMID- 8347764 TI - Effect of various cytokine combinations on induction of non-MHC-restricted cytotoxicity. AB - Efforts were directed to achieve an increased lymphokine-activated non-MHC restricted killing (LAK) activity greater than that induced by rIL-2 alone. Human peripheral blood (PB) and bone marrow (BM)-derived mononuclear cells (MC) were exposed in vitro to multiple cytokine combinations, including rIL-6, rIL-7, rIFN alpha and rIFN-gamma in the presence of either suboptimal or optimal doses of rIL 2. Our results have shown that BMMC are a potential source for induction of increased LAK activity upon exposure to multiple cytokine combinations, whereas PBMC could not be successfully stimulated under the same conditions. Fifty-five to 62% of BM-derived samples stimulated with high dose rIL-2 + rIL-7 or rIL-2 + rIL-7 + rIL-6 + rIFN-gamma exhibited a higher degree of cytotoxicity than BM samples stimulated with rIL-2 alone. Exposure of PB-derived large granular lymphocytes (LGL) to various cytokine combinations led to increased proliferation after stimulation with suboptimal dose of rIL-2 in the presence of rIL-6 and rIL 7. This increase was not observed in induction of cytotoxicity. We suggest that BMMC activated by multiple cytokine combinations could play an active role in improving antitumor response in vivo by contributing to the control of minimal residual tumor cell growth, particularly post-BM transplantation. PMID- 8347765 TI - The effects of thermal injury on serum interleukin 1 activity in rats. AB - Interleukin 1 (IL-1) is present in the blood of burned patients but its pathophysiologic role is not fully understood. Rat models would be useful research tools, if this cytokine could be identified in a complex fluid like blood. We describe a methodology, which revealed IL-1 activity from the serum of burned rats. Serum was collected from 37 rats with 30% total body surface burns and 9 unburned controls. To vary the burn response, the wounds of 17 rats were seeded with nonvirulent Pseudomonas aeruginosa at the time of injury. IL-1 activity was assessed by its capacity to induce IL-2 secretion in murine lymphoma cells (LBRM-33-1A5). Only after the serum had been fractionated, concentrated, and dialyzed, was IL-1 activity uncovered. Sera from burned rats contained five times more IL-1 activity than those from control animals (p < 0.05). There was no difference in serum IL-1 activity between burned and burn-seeded animals. The IL 1 activity was heat labile, and not produced by P. aeruginosa endotoxin, TNF alpha, or endogenous IL-2 in rat serum. These results confirm that serum IL-1 levels are increased following thermal injury, and that there is no apparent relationship between IL-1 levels and infection. The serum preparation scheme presented in this study offers a reasonable approach to the measurement of serum IL-1 levels in rat models of disease and injury. PMID- 8347766 TI - Detection of oncostatin M in human plasma and serum by a sensitive enzyme immunoassay. AB - A sensitive and specific enzyme immunoassay was developed for detecting oncostatin M (OM) in human plasma and serum. The assay utilizes three anti-OM monoclonal antibodies that recognize mutually exclusive epitopes, including a neutralizing epitope. A sensitivity of 24 pg/ml was routinely obtainable. The assay showed no cross-reactivity with leukemia inhibitory factor (LIF) or interleukin-6 (IL-6), other members of the cytokine family that includes OM. The utility of the enzyme immunoassay (EIA) was demonstrated by detecting the time dependent accumulation of OM in plasma from lipopolysaccharide (LPS)-treated human whole blood. The concentration of OM in human sera from normal donors was generally below the detection limits of the assay. However, concentrations of OM greater than 25 pg/ml were found in 17 of 212 serum samples from apparently normal donors. The detection of OM in human plasma and serum demonstrates that the EIA could be a useful tool in examining the role of OM in physiologic and pathologic states. PMID- 8347768 TI - The distribution and nature of colour vision among the mammals. AB - 1. An oft-cited view, derived principally from the writings of Gordon L. Walls, is that relatively few mammalian species have a capacity for colour vision. This review has evaluated that proposition in the light of recent research on colour vision and its mechanisms in mammals. 2. To yield colour vision a retina must contain two or more spectrally discrete types of photopigment. While this is a necessary condition, it is not a sufficient one. This means, in particular, that inferences about the presence of colour vision drawn from studies of photopigments, the precursors of photopigments, or from nervous system signals must be accepted with due caution. 3. Conjoint signals from rods and cones may be exploited by mammalian nervous systems to yield behavioural discriminations consistent with the formal definition of colour vision. Many mammalian retinas are relatively cone-poor, and thus there are abundant opportunities for such rod/cone interactions. Several instances were cited in which animals having (apparently) only one type of cone photopigment succeed at colour discriminations using such a mechanism. it is suggested that the exploitation of such a mechanism may not be uncommon among mammals. 4. Based on ideas drawn from natural history, Walls (1942) proposed that the receptors and photopigments necessary to support colour vision were lost during the nocturnal phase of mammalian history and then re-acquired during the subsequent mammalian radiations. Contemporary examination of photopigment genes along with the utilization of better techniques for identifying rods and cones suggest a different view, that the earliest mammals had retinas containing some cones and two types of cone photopigment. Thus the baseline mammalian colour vision is argued to be dichromacy. 5. A consideration of the broad range of mammalian niches and activity cycles suggests that many mammals are active during photic periods that would make a colour vision capacity potentially useful. 6. A systematic survey was presented that summarized the evidence for colour vision in mammals. Indications of the presence and nature of colour vision were drawn both from direct studies of colour vision and from studies of those retinal mechanisms that are most closely associated with the possession of colour vision. Information about colour vision can be adduced for species drawn from nine mammalian orders.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8347767 TI - A coordinate-free approach to the analysis of growth patterns: models and theoretical considerations. AB - Developmental biology holds keys to our understanding of morphological pattern formation whether these patterns are expressed in the fossil record or among extant species. Though much is known about osseous growth at the cellular level (e.g. Hall, 1991), we have minimal understanding of the coordinated processes that combine to produce a complex, three-dimensional form. We have proposed a framework for the coordinate-free representation of form, a statistical method for comparing and modelling growth trajectories for complex morphologies, and a means for the eventual elucidation of the role of growth in the evolution of morphology. Our method uses the coordinate locations of biological landmarks to represent form as a matrix of all possible linear distances between landmarks, the form matrix. When two forms are expressed in this way, comparison of these forms is accomplished by computing the ratios of like linear distances, the form difference matrix. When the forms being compared are from a growth series, the matrix of ratios is called a growth matrix. Patterns of growth for two groups can be compared by computing the growth difference matrix. We applied growth difference matrix analysis to the study of sexual dimorphism of ontogeny in the M. fascicularis craniofacial skeleton. Growth matrices describing growth in male and female M. fascicularis were presented along with the growth difference matrix that describes sexual dimorphism of growth to underscore the detailed information available from this analytical technique. The method is quite general and can be applied to two- or three-dimensional data sets of landmark coordinates (cross sectional or longitudinal) collected from almost any developing structure. The methods that we propose enable us to go beyond a mathematical summary of the comparison of forms and the comparison of growth patterns. We provide examples of how growth patterns might be used in the study of phylogenetic relationships. Our plans for use of this method in the study of evolutionary change assumes that morphological change in the craniofacial skeleton results from evolutionary change in developmental units (as defined by Atchley & Hall, 1991) that underlie morphological structure. We believe we have the basic tools to ultimately propose informed phylogenies based solely on developmental data. This task requires the identification of 'growth features' and the polarization of these features as primitive or derived. It is also advisable to determine a set of primitive growth features for the groups of interest. This will necessitate the inclusion of outgroups in our growth analysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8347769 TI - Changes in subset specificity of anti-T cell autoantibodies in systemic lupus erythematosus. AB - Relative reactivity of anti-lymphocyte autoantibodies (ALA) from patients with systemic lupus erythematosus (SLE) against CD4+ and CD8+ T cells was studied using C-dependent microcytotoxicity assay. Of 46 SLE sera screened for anti-T cell autoantibodies, 27 sera (59%) showed significant cytotoxic reactivity. Of these, positive correlation between the titer of anti-T cell antibody and CD4/CD8 killing ratio (p < 0.01) was demonstrated. In time course study of individual patients, the CD4/CD8 killing ratio increased and decreased as the disease flared and subsided and was accompanied by parallel changes in the titer of anti-T cell antibody titer. Moreover, as sera were serially diluted, the CD4/CD8 killing ratio decreased in 5 out of 10 sera. These results suggest that discrepancy among reports concerning the subset specificity of anti-T cell antibodies may be due, in part, to differences in the titer of ALA in the sera studied and to the dilution of serum used. PMID- 8347770 TI - Morphological analysis of autoimmune disease in MRL-lpr,Yaa male mice with rapidly progressive systemic lupus erythematosus. AB - We analyzed morphologically autoimmune disease in MRL/MpJ mice bearing both the Yaa and lpr genes (MRL-lpr,Yaa mice), and compared it with that in MRL/MpJ lpr/lpr (MRL-lpr) mice, in order to examine the effect of the Yaa gene on lpr induced tissue-specific immunopathologies. MRL-lpr,Yaa male mice developed glomerulonephritis more rapidly than did MRL-lpr males. The glomerular damage in MRL-lpr,Yaa males, as evaluated by histologic and immunofluorescent methods, was significantly greater than that in age-matched MRL-lpr males. In contrast, no differences in the development of vasculitis and arthritis were noted between the two groups. Pathological examination of the dead mice revealed a similar incidence of lethal glomerulonephritis in the two groups. Lymphoid hyperplasia in the spleen consisted predominantly of unusual T cells (B220+, Thy-1+, CD4-, CD8-) in the two groups, and an increased number of B cells was not found in MRL lpr,Yaa mice. The histological nature of the autoimmune diseases was similar in MRL-lpr,Yaa and MRL-lpr males. These results indicate that the Yaa gene accelerates the development of glomerulonephritis but not that of vasculitis or arthritis, suggesting that the mechanisms underlying the initiation of glomerulonephritis are different from those leading to vasculitis or arthritis in MRL-lpr mice. PMID- 8347771 TI - Effect of syngeneic islet antigen administration on complement-dependent antibody mediated cytotoxicity to islet cells and diabetes onset in diabetes-prone BB/OK rats. AB - Diabetes-prone BB/OK rats aged 30 to 35 days were subjected to three sequential intrasplenic injections of unfractionated homogenate prepared from Langerhans' islets of newborn syngeneic BB/OK rats. Syngeneic islet antigen administration resulted in increased complement-dependent antibody-mediated cytotoxicity (C'AMC) to rat pancreatic islet cells in serum, compared to buffer-treated control animals as detected by 51Cr-release assay. However, the increase of anti-islet cell cytotoxicity neither impaired glucose tolerance nor affected the incidence of diabetes and the age at manifestation. In contrast to BB/OK rats developing diabetes, animals remaining long-term normoglycaemic did not show an enhancement of cytotoxicity to islet cells within twelve days after the first islet antigen injection as revealed retrospectively. In conclusion, humoral mediated anti-islet cell cytotoxicity is not decisively involved in pancreatic beta-cell destruction and promotion of diabetes development in BB/OK rats, but animals becoming diabetic seem to be characterized by a stronger immunological reactivity upon syngeneic islet antigen challenge as indicated by an increase of anti-islet C'AMC compared to long-term normoglycaemic rats. PMID- 8347772 TI - Molecular analysis of abnormal satellite I DNA from a BUF/Mna rat thymoma. AB - BUF/Mna rats develop spontaneous thymomas in an autosomal dominant manner. We constructed recombinant plasmid library of 90 and 185 base-paired (bp) satellite I DNA fragments isolated from BUF/Mna rat thymoma DNA. Four unusual clones containing 93, 95, 95, and 173 bp inserts were isolated by colony hybridization with Wistar rat satellite I DNA. Nucleotide sequence analysis of the inserts of the 4 clones revealed abnormal sequence organization and unusual subunit structure of the rat satellite I DNA. Sequence comparisons between normal and abnormal satellite I DNA suggested that the unusual subunit structure could be generated by the change of the Hinf I recognition sequence to an Eco RI cleavage site, in addition to random deletions, insertions and base substitutions. The heptanucleotide sequence TGGGAAC, which is strictly conserved in normal subunits, was completely lost in all these clones. Southern blot hybridization revealed the amplification of abnormal satellite I DNA in BUF/Mna rat thymomas. PMID- 8347773 TI - Autoantibodies in HIV-infected patients that modulate the cholinergic activity of heart and gut tissue. AB - In human immune deficiency virus (HIV) disease, direct infection of heart tissue with HIV and repeated intestinal infections with opportunistic pathogens are thought to be the main cause of cardiac disease and diarrhoea respectively. A role for autoimmune phenomena may also be involved in the pathogeny of HIV disease. In this study, we demonstrate that immunoglobulins from the A and G classes from HIV positive patients are able to interfere with the function of the muscarinic cholinergic receptors from heart and gut. Both IgA and IgG HIV+ preparations decreased the tension of isolated atria and increased the tension of isolated ileum. The mechanical effect of carbachol was inhibited in both atria and ileum preparations, when they were preincubated with either IgA or IgG HIV+ fractions. An inhibitor of muscarinic cholinergic receptors (atropine) impaired the negative inotropic action of HIV+ immunoglobulins (Ig) on the heart and prevented the positive inotropic effect of HIV+ Igs on ileum. HIV+ IgA fraction was approximately ten fold more potent to interfere with the cholinergic function as compared to the IgG fraction. These results suggest that antibodies present in HIV+ serum may also modulate muscle's cholinergic activity in the heart and ileum from HIV+patients. PMID- 8347774 TI - The induction of J11d antigen on double negative T cells of MRL/Mp-Lpr/Lpr mice by high dose calcium ionophore. AB - Mice homozygous for the lymphoproliferation (lpr) gene spontaneously develop autoimmune syndrome. These mice were characterized by the massive accumulation of double negative (DN) T cells. Although peripheral T cells in normal mice do not express J11d antigen, those abnormal DN T cells in autoimmune-prone mice express J11d antigen. In this study, the mechanisms that control the expression of J11d antigen are analyzed. High concentration of calcium ionophore alone induces the expression of J11d antigen, but not of CD4, CD8, and activation antigens such as interleukin 2 receptor as well as transferrin receptor by J11d- DN T cells from lpr mice. The expression of J11d antigen is primarily regulated at the transcription level rather than the post transcription level. Experiments using metabolic inhibitors reveal that the induction of J11d antigen requires the activation of not only a Ca2+/calmodulin- but also protein kinase C-dependent signaling pathway. Furthermore, J11d- DN thymocytes from control mice share the similar functional property with DN lpr T cells in J11d antigen inducibility. PMID- 8347775 TI - Adhesion of cerebral endothelial cells to lymphocytes from patients with multiple sclerosis. AB - To investigate the factors regulating the entry of lymphocytes into the brain, we assessed the adhesion in vitro of 51Cr labelled lymphocytes from peripheral blood of patients with multiple sclerosis (MS) to human cerebral endothelial cells, and evaluated the effect on the adhesion of endothelium activated by interferon-gamma (IFN-gamma), lipopolysaccharides (LPS), interleukin-1 (IL-1) and tumor necrosis factor (TNF). Patients with acute relapsing MS during an exacerbation showed significant increase in MNC adherence to cerebral endothelial cells as compared with controls (p < 0.001). MNC adherence to cerebral endothelial cells activated by IFN-gamma or LPS, was significantly increased as compared to the controls (p < 0.01). MNC adherence to endothelial cells was not blocked by antibodies against the intercellular adhesion molecule-1 (ICAM-1), but was blocked by lymphocyte function-associated antigen-1 (LFA-1). The increased adherence observed in patients with acute relapsing MS during an exacerbation would modulate the migration of lymphocytes across the blood-brain barrier (BBB). PMID- 8347776 TI - Silicone and autoimmunity. PMID- 8347777 TI - Insulin autoimmune syndrome; HLA genes may be a marker of disease heterogeneity. PMID- 8347778 TI - Helicobacter pylori, dietary factors, and atrophic gastritis in five Japanese populations with different gastric cancer mortality. AB - In a cross-sectional study of 634 men aged 40 to 49 years, randomly selected from five areas of Japan with different rates of gastric cancer mortality, 121 men of 624 evaluated were diagnosed as having atrophic gastritis through serum pepsinogen I < 70 ng/ml and the pepsinogen I (PGI)/pepsinogen II (PGII) ratio < 3.0. We examined the relation of Helicobacter pylori (H. pylori) antibodies and dietary factors, including plasma level of antioxidant micronutrients, to the presence of atrophic gastritis. Presence of H. pylori IgG antibodies was associated with increased risk of atrophic gastritis (odds ratio [OR] = 1.9, 95 percent confidence interval [CI] = 1.1-3.3). As the level of plasma beta-carotene increased, we found a steady decrease in the risk of atrophic gastritis (OR for second quartile = 0.7, third quartile = 0.6, fourth quartile = 0.4, with CI = 0.2 0.8). Frequent intake of yellow vegetables also was associated with lower risk, while frequent intake of soybean products was related to increased risk. Although H. pylori antibodies, beta-carotene level, and intake of soybean products were all significant in the multivariate analysis, these factors did not explain the differences in atrophic gastritis prevalence among the five regions. The analysis of these risk factors in relation to each pepsinogen marker showed that although both H. pylori infection and low plasma beta-carotene were associated with the decreased level of serum PGI/II ratio, the former was derived from the increase of PGII, which is common in early stage of atrophic gastritis, and the latter from the decrease of PGI, which is specific to severe atrophic gastritis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347779 TI - Helicobacter pylori infection and chronic atrophic gastritis among Japanese blood donors: a cross-sectional study. AB - To evaluate an association between Helicobacter pylori (H. pylori) infection and chronic atrophic gastritis (CAG), an established precursor of gastric cancer, we performed a cross-sectional study using IgG antibody against H. pylori and pepsinogens of blood donors in four prefectures in Japan. Although a geographic correlation between the age-adjusted prevalence rates for H. pylori infection and those for CAG was not seen, the age-adjusted odds ratios (OR) of H. pylori infection for CAG were high in each area (around five for men and from four to 12.6 for women). The association between them weakened with advancing age; the ORs in the youngest age group (16-29 yrs) and in the oldest age group (50-64 yrs) were 12.5 and 2.8 for men, and 11.5 and 5.2 for women, respectively. These findings suggest that H. pylori infection is strongly associated with CAG, while there are some other factors interacting in the development of CAG. A prospective cohort study in which CAG and H. pylori infection are taken into account will be necessary to assess the risks of gastric cancer. PMID- 8347780 TI - Occupational physical activity, socioeconomic status, and risks of 15 cancer sites in Turkey. AB - A multiple-site case-control study of 15 cancers (stomach; colon; rectum; larynx; lung; melanoma; skin; female breast; male breast; cervix; ovary; uterus; prostate; testis; and bladder) was conducted to evaluate their association with occupational physical activity and socioeconomic status (SES). A hospital-based study population (3,486 male cases and 379 female cases, and 2,127 male and 244 female controls) was established in an oncological treatment center in Istanbul, Turkey, from 1979-84. Assessment of physical activity and SES was based on job titles held by the study subjects. Two measures of physical activity were developed based on energy expenditure and 'sitting time' during working hours. Observed risks were adjusted for age, smoking, and SES. Elevated risks were observed among workers who held sedentary jobs for cancers of the colon (odds ratio [OR] = 1.6), rectum (OR = 1.3), melanoma (OR = 1.9), male breast (OR = 1.4), prostate (OR = 5.0), and ovary (OR = 2.0). Cancers of the cervix and uterus showed significantly decreasing risks with decreased activity. Risks of cancers of the colon, rectum, larynx, ovary, and melanoma were enhanced after risks for physical activity indices were adjusted for SES, while the associations between physical activity and cancers of the prostate, cervix, and uterus were weakened after SES adjustment. Risks of melanoma rose significantly with both activity indices after SES adjustment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347781 TI - Alcohol consumption and postmenopausal endometrial cancer: results from the Iowa Women's Health Study. AB - At least three case-control studies have examined the association between alcohol consumption and endometrial cancer; two studies showed inverse associations, and a third a positive association. To our knowledge, no prospective studies of this association have been reported. The association between alcohol and endometrial cancer was examined in the Iowa Women's Health Study (United States), a prospective study of postmenopausal women. Information on alcohol consumption and other variables was obtained through a mailed questionnaire in January 1986. Through December 1990, 167 incident endometrial cancer cases occurred in the at risk cohort of 25,170 women. Multivariate-adjusted relative risks (RR) and 95 percent confidence intervals (CI) were computed using Cox proportional hazards regression controlling for age, body mass index (BMI), parity, age at menopause, and noncontraceptive estrogen use, and to determine multiplicative interactions. The RRs of endometrial cancer associated with < 4.0 and > or = 4.0 g of alcohol per day compared with abstainers were 0.7 (CI = 0.5-1.1) and 1.0 (CI = 0.7-1.6), respectively. No statistically significant association between endometrial cancer and consumption of either beer, wine, or liquor was observed. There was no interaction between alcohol and any other endometrial cancer risk factors, including BMI or noncontraceptive estrogen use. These data do not support an association between alcohol and endometrial cancer among postmenopausal women. PMID- 8347782 TI - The association of height, weight, menstrual and reproductive events with breast cancer: results from two prospective studies on the island of Guernsey (United Kingdom). AB - The association with breast cancer of menstrual and reproductive events, family history of breast cancer, and body size have been studied on two cohorts of 6,706 volunteers on the island of Guernsey (United Kingdom), 168 of whom had breast cancer detected during follow-up. The median follow-up time of the non-cases was 21 years in the first study and 10 years in the second. A time-dependent Cox regression model was fitted to the data with age as the time-dependent variable in order to represent the effect of changing menopausal status. Other variables examined in the model were age at menarche, parity, age at first birth, family history of breast cancer, height, weight (both directly measured), relative weight (weight [kg]/height[m]), and Quetelet's body mass index (weight[kg]/height[m]2). Interactions between age and all other covariates also were examined. Family history was found to be the most important risk factor for women aged less than 51 years (relative risk [RR] = 3.5, 95 percent confidence interval [CI] = 2.0-6.0), and intervals between menarche and first birth longer than 14 years were found to increase significantly the risk of breast cancer in women older than 61 years (RR = 2.4, CI = 1.3-4.4). Height was the only indicator of body size which was associated significantly with risk of breast cancer, the estimated regression coefficient indicating an increase in risk of about 70 percent for women on the 90th centile of height relative to those on the 10th centile. A survey of the literature showed that the association between risk of breast cancer and height was found in those studies which used direct measurements of height but not in others which used self-reported values. PMID- 8347783 TI - Childhood leukemia incidence in the vicinity of La Hague nuclear-waste reprocessing facility (France). AB - The incidence of leukemia is examined in young people (aged under 25 years) living within a 35 km radius of the French nuclear-waste reprocessing plant operating in La Hague, Normandy. During the period 1978-90, a total of 23 cases was diagnosed, giving an incidence rate of 2.99 per 100,000 which is close to the expected rate. In the 'canton' in which the nuclear plant is located, three cases of leukemia were observed compared with 1.2 expected, giving a standardized incidence ratio of 2.5. This nonsignificant finding is compatible with no increased risk and also with a sevenfold excess risk. Therefore, it reinforces the necessity of conducting a case-control survey, which is now planned, to assess the part played by occupational radiation exposure in leukemia incidence for this French area. PMID- 8347784 TI - Alcoholic beverage consumption and risk of breast cancer in Spain. AB - The relation between alcoholic beverage consumption and risk of breast cancer was examined. We used data from a population-based, case-control study that included almost all incident cases occurring in five Spanish regions from February 1990 to July 1991. A total of 762 women between 18 and 75 years of age, with a histologically confirmed, first diagnosis of breast cancer, were compared with 988 control women. Alcoholic beverage intake was measured by an interviewer administered, semiquantitative food-frequency questionnaire. We used 'nondrinkers' as the reference category and divided the remainder into four categories according to alcohol intake. The multiple logistic analyses included not only alcohol intake but also possible confounding factors such as total caloric intake, age, socioeconomic status, and reproductive and medical histories. Even at moderate levels of alcohol intake (less than 8 g/day), a 50 percent increase in risk of breast cancer was found. The trend across categories of intake was statistically significant for wine and distilled drinks, as well as total alcohol intake. Consumption of 20 g or more of alcohol per day was associated with a 70 percent elevation in breast cancer risk compared with that of nondrinkers (adjusted relative risk (RR) = 1.7, 95 percent confidence interval = 1.3-2.3). Although the magnitude of the RR observed in our study was modest, our findings provide further support for a positive association between alcohol consumption and risk of breast cancer. PMID- 8347785 TI - Incidence trends for cancers of the breast, ovary, and corpus uteri in urban Shanghai, 1972-89. AB - Incidence data from the Shanghai (People's Republic of China) Cancer Registry were used to assess the temporal trends of three major female cancers during 1972 89. Rates for cancers of the breast, corpus uteri and, to a lesser extent, ovary rose over the study period. The increases in breast and ovarian cancer were most pronounced among women under age 50, whereas those for corpus uteri cancer were restricted generally to those aged 55 to 69 years. When considered by cohort year of birth, risk of breast and ovarian cancers rose among women born since 1925 and 1935, respectively, but little evidence of cohort effect was apparent for corpus uteri cancer. Potential explanations for these patterns are explored. PMID- 8347786 TI - Prior medical conditions and the risk of adult leukemia in Shanghai, People's Republic of China. AB - A population-based case-control interview study of 486 adult leukemia cases and 502 healthy controls was carried out in Shanghai, People's Republic of China during 1987-89 to evaluate the etiologic role of prior medical conditions, medications, and diagnostic X-rays. Risks were examined separately for 236 cases with acute non-lymphocytic leukemia (ANLL), 79 with chronic myeloid leukemia (CML), 81 with acute lymphocytic leukemia (ALL), and 21 with chronic lymphocytic leukemia (CLL). Little difference was found between cases and controls for prior history of diabetes, hypertension, allergic conditions, most medications, and diagnostic X-rays. A few significant associations were observed for appendectomy, tuberculosis, and for several other chronic disorders with specific leukemia cell types, but the odds ratio estimates for most of these ranged from two to three and, with the exception of the two specified above, were based generally on five or fewer exposed controls. In contrast to an association with childhood leukemia in Shanghai, prior use of chloramphenicol was not linked with ANLL or other forms of adult leukemia. Further research is needed to clarify the relation of specific medical conditions and exposures with particular subtypes of leukemia, and to examine reasons for the low incidence of CLL in China and other Asian populations. PMID- 8347789 TI - Oral contraceptives and malignant melanoma. PMID- 8347787 TI - Tobacco, ethanol, coffee, pancreatitis, diabetes mellitus, and cholelithiasis as risk factors for pancreatic carcinoma. AB - A hospital-based case-control study of pancreatic cancer was conducted in Athens in 1991-92. One hundred and eighty-one patients operated on for cancer of the exocrine pancreas in eight teaching hospitals formed the case series, whereas hospital patient controls and hospital visitor controls formed two independent comparison series. Cases and controls were matched by hospital, gender, and age in a 1:1:1 ratio, and every matched triplet was interviewed in person by the same researcher. Results indicate that tobacco smoking increased the risk of pancreatic cancer, whereas neither coffee drinking nor consumption of alcoholic beverages were associated with the disease. Diabetes mellitus, cholelithiasis, and pancreatitis were associated positively with risk of pancreatic cancer, whereas allergic asthma was inversely (but not significantly) related to the disease. There was a suggestion that earlier age at menarche was associated with increased risk of pancreatic cancer and that parous women were at lower risk. No consistent associations were noted with respect to gastrectomy, other medical conditions or operations, birth order, height, weight, broad occupational groups, or other reproductive variables. The two comparison series were remarkably similar with respect to the whole spectrum of the study variables. PMID- 8347788 TI - Smoking and bladder cancer risk in blacks and whites in the United States. AB - A population-based case-control study of bladder cancer (2,982 cases and 5,782 controls) conducted in 10 areas of the United States examined the effect of smoking as a risk factor among Blacks and Whites, after adjustment for occupation and other potential confounders. Although the overall risk for smoking was slightly higher in Blacks than Whites (relative risk = 2.7 and 2.2, respectively), this difference was not statistically significant. Estimation of risk by dose and currency of exposure revealed no consistent racial disparities in smoking-related risks. Race-specific, attributable risk estimates indicated that nearly half of bladder cancers among both Blacks and Whites could have been prevented by elimination of smoking. PMID- 8347790 TI - Influence of Mg2+ on the in vitro responsiveness of adenylate cyclase from hearts of aging rats. AB - The influence of [Mg2+] on the basal or stimulated activity of adenylate cyclase from the hearts of young (1 month old) and aged (24 months old) rats has been investigated in vitro. The basal activity of cardiac adenylate cyclase, and its responsiveness to stimulatory or inhibitory effectors, declined with age. This is probably due to alterations at the catalytic moiety of the signal transduction system, such as an impairment in the affinity of the catalytic moiety for ATP and a lower capacity of the catalytic moiety to bind activated stimulatory (Gs) or inhibitory (Gi) guanine nucleotide binding proteins. Compared to the enzyme from the heart of aged rats, unstimulated adenylate cyclase from the heart of young rats was more sensitive to an increase in [Mg2+] in the incubation mixture, as shown by a greater increase in basal activity and in the affinity of the enzyme for ATP. An increase in [Mg2+] counteracted the inhibitory effect of spermine on adenylate cyclase more effectively in young rats than in aged rats. On the other hand, an increase in [Mg2+] facilitated the stimulation of adenylate cyclase by Gpp(NH)p, isoproterenol and forskolin more in aged rats than in young rats. GDP beta S prevented the positive effect of high [Mg2+] on the stimulation of adenylate cyclase by forskolin, suggesting that an increased [Mg2+] favors the activation of Gs or the formation of functional complexes between the catalytic moiety and Gs. We suggest that aging leads to a higher requirement for Mg2+ at the allosteric site on the catalytic moiety whose occupancy is essential for the full expression of stimulated activity. PMID- 8347791 TI - Age-related changes in cardiac mitochondrial energetics under the influence of calcium in rat. AB - Mitochondria extracted from the hearts of Wistar rats aged 6 and 24 months showed similar values for the respiratory control index (RCI), state 3 oxygen consumption (QO2) and ADP/O measured using glutamate or succinate as substrates; with the exception that the QO2 of the aged rats was lower than that of the young rats in the presence of glutamate. The consumption of O2 induced by 2 oxoglutarate and ADP was similar in both age groups. Concentrations of external free Ca2+ ranging from 0.2 to 0.8 microM produced an increase in O2 consumption and ATP formation in the young mitochondria, with a maximum effect at 0.2 microM external free Ca2+. Little or no change in O2 consumption and ATP formation was evident in aged mitochondria following incubations in concentrations of external free Ca2+ ranging from 0.2 to 0.8 microM. The continuous rate of formation of ATP, measured in the presence of 0.2 microM external free Ca2+ using a luminescence method, confirmed the previous results. This study indicates that the cardiac mitochondrial phosphorylating system of aged rats is poorly sensitive to variations in external free calcium. PMID- 8347792 TI - Myocardial infarction, cardiac anatomy and ventricular loading. AB - To see whether the hypertrophic response of the surviving myocardium after infarction leads to a complete reconstitution of ventricular mass, the left coronary artery was ligated in rats and the animals killed one month later. In infarcts affecting an average of 38% of the free wall of the left ventricle, the ratio of wall thickness to chamber radius remained essentially constant. On the other hand, the ratio decreased significantly in the presence of infarcts involving an average of 60% of the ventricular wall. In addition, inadequate growth adaptations were detected in both groups of infarcts with respect to myocyte volume and length and to capillary volume and length. These defects in the regeneration of myocardial structures were associated with elevations in diastolic wall stress which were more prominent in the larger infarct group. The limited growth reaction of the myocyte and vascular compartments may be implicated in the persistence of cardiac dysfunction and failure late after infarction. PMID- 8347793 TI - Hibernating and stunned myocardium. AB - The term "hibernating" myocardium has been introduced to indicate the presence of regional asynergy due to persistent hypoperfusion, which can be reversed after revascularization. The mechanisms underlying the prolonged functional adaptation of myocardial cells to hypoperfusion are still not clear, although preliminary experimental data indicate that a reduced availability of intracellular Ca++ may play an important role. The identification of hibernating myocardium may have therapeutic implications, since it has been demonstrated that the revascularization of hibernating myocardial territories may lead to regional and global improvement of systolic left ventricular function. The noninvasive identification of hibernating myocardium can be accomplished by positron emission tomography, which demonstrates the presence of preserved metabolic activity in hibernating myocardial territories. However, exercise 201thallium scintigraphy, using the reinjection technique, with a quantitative regional analysis of 201thallium uptake, has also been reported to provide information comparable to that obtained by positron emission tomography. "Stunning" of the myocardium indicates a condition of transient impaired regional systolic function, following an episode of ischemia. The mechanisms determining the slow recovery of function after ischemia are still not completely understood. Experimental data suggest in this case a reduced Ca++ affinity of the myofibrils and a reduced maximal calcium activated force. PMID- 8347794 TI - Developmental changes in the myosin composition of guinea pig ventricular muscle. Relation to thyroid state and mechanical properties. AB - In a variety of mammalian species, thyroid hormone regulates the contractile properties of the heart as well as the expression of the alpha and beta heavy chains of myosin. We have previously shown that the plasma levels of thyroid hormone reach a peak immediately after birth in guinea pigs and decline with maturation. We therefore studied age-related changes in the expression of the myosin heavy chains in the guinea pig ventricle in relation to the ventricular mechanical properties and the levels of thyroid hormone. The composition of the myosin heavy chains was characterized by gel electrophoresis and immunoblotting. Anti-beta-chain antibody stained equally myosins from newborns (0-5 days) and adults (75-90 days), while anti-alpha-chain positively decorated only the myosins of euthyroid newborns or of hyperthyroid adults, but not myosins of embryos, hypothyroid newborns or hypothyroid adults. Myosin of euthyroid adults was faintly stained by anti-alpha-chain. The alterations in the composition of myosin corresponded with the "thyroid state" of these groups. The plasma levels of total T3 were 24.3 +/- 2.7, 9.04 +/- 1.2 and 139.0 +/- 9.3 ng/dl (mean +/- SEM) in the euthyroid, hypothyroid and hyperthyroid adults, respectively. In euthyroid and hypothyroid newborns, the plasma levels of T3 were 56.5 +/- 11.9 and 26.5 +/- 9.8 ng/dl, respectively. Within each age group the thyroid state corresponded with maximal twitch tension (Tmax), rates of development of tension and relaxation, time to peak tension and rate of activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347795 TI - Heterogeneity of smooth muscle in bovine coronary arteries. AB - The monoclonal antibodies TT-1 against troponin T and TI-1 against troponin I of cardiac muscle, together with Western blots and immunofluorescence techniques, were used to evaluate the presence of troponin-like antigens in the smooth muscle cells of bovine coronary arteries. The walls of the left coronary artery before the bifurcation, its circumflex and descending branches, the right coronary artery, and the small branches of coronary arteries and the intramural arterial vessels were found to be homogeneously stained by the TT-1 antibody. Conversely, with the TI-1 antibody, differences were observed in the distribution of the TnI like antigen among the smooth muscle cells of extramural and intramural vessels. Heterogeneity of the smooth muscle cells of the coronary artery was also evident in the medial layer of large vessels near the branching points, where an intimal thickening was consistently observed. Double immunofluorescence assays with anti troponin antibodies in vivo and in vitro indicated a distinct intracellular localization of troponin T and troponin I immunoreactivities in vascular smooth muscle cells. The data are compatible with the existence of distinct troponin like antigens in smooth muscle cells of bovine coronary arteries whose distribution is in part related to the extramural or intramural localization of blood vessels. PMID- 8347796 TI - Age-dependent changes in myocardial susceptibility to ischemic injury. AB - We studied the relation between age and the heart's ability to tolerate ischemia. Groups of 5-7 isolated Langendorff perfused hearts from neonatal (5 days old), immature (11-44 days old), and adult (54 days old) rats, were subjected to 60 minutes of global ischemia and 60 minutes of reperfusion at 37 degrees C. Pre ischemic left ventricular developed pressure was 54 +/- 1, 56 +/- 2, 59 +/- 4, 80 +/- 3, 91 +/- 9, 91 +/- 8, 94 +/- 3, 101 +/- 10, 107 +/- 8 and 132 +/- 4 mmHg in the 5, 11, 14, 18, 23, 26, 33, 40, 44, and 54 day old groups, respectively. Left ventricular developed pressure recovered to 65 +/- 13, 69 +/- 4, 103 +/- 14, 84 +/- 10, 81 +/- 3, 59 +/- 11, 42 +/- 10, 34 +/- 6, 34 +/- 6 and 25 +/- 7% respectively. Ischemia-induced contracture was greater in adult hearts and the time-to-onset and the time-to-peak contracture decreased with increasing age. Leakage of creatine kinase after ischemia correlated poorly with the recovery of contraction. Left ventricular end-diastolic pressure, at the end of 60 minutes of reperfusion, increased in an age-dependent manner from a pre-ischemic value which was set at 2-8 mmHg to 14 +/- 4, 22 +/- 2, 21 +/- 5, 27 +/- 3, 47 +/- 16, 52 +/- 7, 71 +/- 7, 81 +/- 9, 73 +/- 5, and 82 +/- 8 mmHg in the 5, 11, 14, 18, 23, 26, 33, 40, 44, and 54 day old groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347797 TI - Functional and molecular changes in FoF1 ATP-synthase of cardiac muscle during aging. AB - We have studied the functional and molecular changes of mitochondrial FoF1 ATP synthase of cardiac muscle during aging. ATP hydrolase activity was lower in sonic submitochondrial particles prepared from hearts of senescent rats (24 months) than in those prepared from hearts of adult rats (12 months). Oligomycin sensitive proton conduction of cardiac submitochondrial particles was greater in senescent rats than in adult rats. The beta subunit of F1, detected immunologically in submitochondrial particles, was less in senescent rats than in adult rats. Exposure of cardiac submitochondrial particles from adult rats to free radicals, generated by 60Co, resulted in inactivation of ATP hydrolase activity and a decreased content of F1. The structural and functional alterations of mitochondrial FoF1 ATP synthase during aging may be expected to affect energy metabolism, and our results suggest that they could originate from the action of free radicals generated in the inner mitochondrial membrane. PMID- 8347799 TI - British Society for Clinical Cytology. Programme and abstracts of the 32nd annual scientific meeting. Leeds, U.K., 11-15 September 1993. PMID- 8347798 TI - Coronary hemodynamics during isometric handgrip and atrial pacing in patients with angina pectoris compared to healthy men. AB - The responses in coronary blood flow and the relative myocardial extraction of oxygen to atrial pacing (causing mainly an increase in heart rate) and isometric handgrip (causing mainly an increase in pressure) were studied in patients with angina and in young and middle-aged healthy men. The myocardial extraction of oxygen and coronary sinus flow were measured by catheterizing the coronary sinus, using a catheter with thermistors for the measurement of flow by thermodilution and electrodes for atrial pacing. In the healthy men the increase in the consumption of oxygen was covered entirely by an increased coronary blood flow during both provocations, with no change in the arteriovenous oxygen difference during handgrip and a decrease during pacing. There was no significant difference in the reaction between younger and older men. In the patients with angina the increased consumption of oxygen during pacing was covered by an increased coronary blood flow with an unaltered arteriovenous oxygen difference, while during handgrip both the coronary blood flow and arteriovenous oxygen difference increased. It is concluded that during handgrip, compared to the artificial increase in heart rate, the myocardium is more dependent upon an increased relative extraction of oxygen to cover an increase in the requirement for oxygen. This may be due to a higher intramyocardial pressure. Patients with coronary heart disease are more dependent than healthy men on an increase in the relative myocardial extraction of oxygen. This may be related to a lower effective perfusion pressure because of the coronary arterial obstructions or to an increased intramyocardial pressure and a relatively shorter duration of diastole because of the impaired cardiac function. PMID- 8347801 TI - Lesions in four parts of the basal forebrain change basic behaviour in rats. AB - Subdivisions of the basal forebrain (BF) are postulated to be differently involved in the regulation of behavioural functions. We compared 16 parameters of rat open field behaviour before, 10 days and 60 days after lesions in four BF subdivisions, the anterior and the posterior nucleus basalis magnocellularis (NBMa, NBMp), the vertical and the horizontal diagonal band nucleus (VDB, HDB) with sham-operated control rats. Every lesion type caused a significantly different pattern of significant behavioural changes. VDB and NBMp lesions both produced different patterns of ambulatory and exploratory hyperactivity, whereas NBMa lesions caused hypoactivity. Changes after HDB lesions were relatively small. The rate of habituation also shared changes that differed according to the lesion site. These changes in basic unlearned behaviour are likely to interact with more complex functions such as cognitive processes, learning and memory. PMID- 8347802 TI - Nitric oxide activates buccal motor patterns in Lymnaea stagnalis. AB - The mollusc, Lymnaea stagnalis, has been used as a model to study the mechanisms of nitric oxide (NO)-dependent processes in the CNS. Putative NO-containing neurones in Lymnaea are localized in the buccal ganglia, predominantly in areas where sensory neurones known to regulate feeding are found. The NO-generating substance, S-nitrosocysteine (S-NC, 5 x 10(-5)-10(-3 M) activates feeding movements of the buccal mass and modulates the activity of buccal motoneurones. An inhibitor of NO synthase, NG-methyl-L-arginine (10(-4) M) decreases the frequency of background buccal movements and has opposite effects to S-NC on the buccal motoneurones. We suggest that NO is a messenger in the CNS of Lymnaea and may be involved in coordination of feeding motor patterns. PMID- 8347800 TI - Maternal nicotine exposure enhances cutaneous axon reflexes in the neonatal rat. AB - Chronic nicotine exposure enhances axon reflexes in adult rats. Since smoking mothers expose their infants to nicotine, this study investigated whether late gestational and or lactational maternal nicotine exposure affects neonatal axon reflexes. Osmotic pumps, implanted subcutaneously in adult female rats, delivered either nicotine (5 mg kg-1 day-1) or saline. Axon reflex responses of infant progeny, evoked by iontophoresis of 2 mC acetylcholine, were measured by laser Doppler flowmetry. Nicotine-exposed infants showed significantly enhanced axon reflexes during both gestational and lactational nicotine exposure, which recovered after exposure ceased. Controls did not exhibit these changes. Maternal nicotine exposure reversibly sensitized nicotinic cholinoceptors on infant cutaneous sensory nerves, but not muscarinic cholinoceptors on vascular endothelium. This may result from upregulation of cutaneous nicotinic cholinoceptors. PMID- 8347803 TI - The localization of cholecystokinin mRNA in embryonic striatal tissue grafts: further evidence for the presence of non-striatal cells. AB - We have studied by in situ hybridization histochemistry the mRNA expression of preprocholecystokinin (CCK) in grafts of foetal striatal tissue neurones implanted into the ibotenic acid lesioned adult rat neostriatum. Animals were studied at 30 and 90 days after implantation. Using a 35S-labelled 'antisense' oligonucleotide (45-mer) probe complementary to the rat CCK cDNA we observed a dense hybridization signal for CCK mRNA in the striatal eminence in developing embryos and in all the striatal grafts examined; no CCK mRNA expressing cells were found in the normal neonatal or adult rat neostriatum. However, CCK mRNA was heavily expressed in other areas of the host brain including the somatosensory cortex, the claustrum, primary olfactory cortex and endopiriform cortex. The germinal cell layer of the striatal eminence is the source of origin for these non-striatal cell groups as well as for cells destined to form the neostriatum. The present results suggest that CCK mRNA expression provides an unambiguous marker for many of the non-striatal cells in 'striatal' grafts. PMID- 8347804 TI - Age-related changes of DRG neuronal attachment to extracellular matrix proteins in vitro. AB - Attachment of dorsal root ganglion (DRG) neurones from 3-month-old (young adult) and 24-month-old (aged) mice to the following substrates was evaluated after 6 h in culture: (1) poly-L-lysine (PL), (2) PL + type I collagen (CL-I), (3) PL + type IV collagen (CL-IV), (4) PL + laminin (LM) and (5) PL + fibronectin (FN). In the young adult mice, each substrate coated onto PL, significantly increased the ratio of attachment, compared with PL alone. In the aged mice, CL-I and LM, but not CL-N or FN improved the attachment. There was no difference in cell survival or neurite extension after 48 h in culture between the two groups of mice. These results suggest that ageing causes selective changes of the neuronal cell-surface receptors respective to extracellular matrix proteins such as CL-IV and FN. PMID- 8347805 TI - Event-related potentials and recognition memory within the 'levels of processing' framework. AB - Event-related potentials (ERPs) were recorded from nine subjects during an incidental memory paradigm. During the study phase subjects were engaged in two tasks requiring semantic and rhyming decisions. During the test phase, subjects were required to decide on each of 320 trials if the word was 'new' (never before presented) or 'old' (seen previously). Results showed that semantic old words were more often recognized than rhyming ones. ERPs to new words were more negative than ERPs to old words in the 400-800 latency range. ERPs to semantic old words were more positive than ERPs to rhyming ones in the same latency range. The difference between ERPs to semantic and rhyming old words confirms a relationship between ERPs and memory. PMID- 8347806 TI - Functional magnetic resonance imaging of Broca's area during internal speech. AB - Conventional gradient-echo magnetic resonance imaging (MRI) at 4 Tesla was used successfully to study the activity of Broca's area during internal speech word generation in healthy right-handed volunteers. Activity was demonstrated in the internal gray matter surrounding the ascending ramus of the lateral sulcus, deep to the cortical surface representation of Broca's area, in all the subjects. These studies demonstrate the capability of functional MRI to non-invasively map language related cognitive functions. Such functional mapping has value for both the study of basic neuroscience and neurosurgical planning. PMID- 8347807 TI - Proconvulsant and anticonvulsant effects of Evans blue dye in rodents. AB - The effect of i.c.v. administration of Evans blue to sound sensitive DBA/2 mice and to genetically epilepsy-prone rats was studied. In mice, Evans blue (3.3-52 nmol) induced: hyperlocomotion, wild running, scratching, clonic muscle spasms, tonic seizure (latency 10-45 min), followed by death or recovery. The CD50 value for clonic seizures for Evans blue was 35(23-53) nmol. Pretreatment (45 min) with Evans blue (13-52 nmol, i.c.v.) dose-dependently reduced the incidence of sound induced seizures in DBA/2 mice (ED50 value against clonic seizures = 30 [15-58] nmol, i.c.v). In rats, Evans blue (104 nmol, i.c.v.) induced electroencephalographic seizures in the hippocampus and cortex and behavioural limbic seizures with a latency of 15-20 min. A reduction in the mean score (from 5 to 2-3) for behavioural seizures was observed which lasted for 4-5 days in rats electrically-kindled daily in the hippocampal CA3 subsector. Sound-induced clonic seizures in kindled and non-kindled rats were reduced for 3-4 days after administration of Evans blue (104 nmol, i.c.v.). PMID- 8347808 TI - Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists. AB - Four kinds of heteromeric N-methyl-D-aspartate (NMDA) receptor channels, the epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 3/zeta 1 and epsilon 4/zeta 1 channels, were expressed in Xenopus oocytes and their sensitivities to various non-competitive antagonists were examined. The epsilon 1/zeta 1 and epsilon 2/zeta 1 channels were more sensitive to (+)MK-801 (dizocilpine) than the epsilon 3/zeta 1 and epsilon 4/zeta 1 channels, whereas the sensitivities to phencyclidine (PCP), ketamine and N-allylnormetazocine (SKF-10,047) were only slightly variable among the four epsilon/zeta channels. Furthermore, the replacement by glutamine or arginine of the conserved asparagine residue in segment M2 of the epsilon 2 and zeta 1 NMDA receptor channel subunits reduced the sensitivities to PCP, ketamine and SKF-10,047, though to different extents. These results, together with previous findings, suggest that these non-competitive antagonists as well as (+)MK-801 and Mg2+ act on a common site. PMID- 8347809 TI - Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti heat shock protein-70 antibody. AB - To clarify the role of heat shock protein-70 (HSP70) in ischaemic tolerance following pretreatment with sublethal cerebral ischaemia, we examined whether the induction of tolerance in the gerbil hippocampus is inhibited by quercetin, an inhibitor of HSP70 expression, or anti-HSP70 antibody. A 3 min period of forebrain ischaemia was induced following pretreatment with 2 min of ischaemia and 3 days of reperfusion. Quercetin or anti-HSP70 antibody was continuously infused into the left lateral ventricle using an implanted osmotic minipump started 3 h after or 2 h before the first ischaemia. The animals were killed 4 days after the second ischaemia for histological observations. Both agents produced no neuronal damage in the brain following a single 2 min period of ischaemia. The neuronal density of the CA1 hippocampus in animals subjected to treatment with quercetin and anti-HSP70 antibody was significantly lower than vehicle-treated animals but were significantly higher than animals with a single 3 min period of ischaemia. Thus, the present study showed that quercetin and anti HSP70 antibody prevent the induction of ischaemic tolerance. The result suggests that HSP70 expression, at least in part, plays a role in the induction of ischaemic tolerance. PMID- 8347810 TI - Timing the excitotoxic induction of heat shock protein 70 transcription. AB - The time course of heat-shock protein 70 (HSP70) transcriptional induction was compared with neuronal- and non-neuronal-specific mRNAs following intrastriatal quinolinate (QA) injection. Within one hour of QA exposure, immediate-early gene (IEG; c-fos) activation preceded slight increases in glutamic acid decaroxylase (GAD) mRNA levels. However, glial fibrillary acid protein (GFAP) and HSP70 mRNA levels remained constant. After one hour, HSP70 mRNA levels surged 6 fold during a delayed transcriptional phase that was induced between 4-12 hours. This phase was characterized by massive increases in c-fos and GFAP mRNAs while GAD transcripts fell drastically suggestive of neuronal death. Therefore HSP70 genes may play an important role in glial/immune activation following rapid excitotoxic damage by direct injections of quinolinate. PMID- 8347811 TI - Apomorphine induced hypothermia, stereotypy and changes in dopamine D2 mRNA expression. AB - The changes in DA-D2 receptor mRNA expression following apomorphine induced hypothermia and stereotypy were determined. Rectal temperatures and stereotypy were measured daily after apomorphine injection to Sprague-Dawley rats for 7 days. DA-D2 mRNA expression was determined by Northern blot analysis. Apomorphine caused a dose dependent decrease and increase in rectal temperatures and stereotypy respectively. Northern blot analysis indicated a relative abundance of the DA-D2 receptor message at the high and a reduction at the lower dose of apomorphine. The result showed that the agonist activity could influence the expression of DA-D2 receptor mRNA. PMID- 8347812 TI - Correlation between peri-infarct DC shifts and ischaemic neuronal damage in rat. AB - The effect of peri-infarct depolarizations on ischaemic injury was studied in rats submitted to 3 h occlusion of the left middle cerebral artery (MCA). The number of depolarizations varied from 1 to 8 and infarct volume from 37 to 159 mm3. The correlation between the two variables revealed a highly significant linear relationship (r = 0.800; p < 0.005), each depolarization accounting for an increase in infarct volume by about 13 mm3. The aggravating effect of repeated depolarizations was also demonstrated by the gradual increase in cortical DC shift duration, in EEG amplitude recovery time, and in EEG delta power with increasing number of depolarizations. Suppression of peri-infarct depolarizations is a rational approach for reducing the severity of ischaemic stroke. PMID- 8347813 TI - Protein kinase A inhibitors prevent the maintenance of hippocampal long-term potentiation. AB - The possible involvement of cAMP-dependent protein kinase A (PKA) in mechanisms of long-term potentiation of the Schaffer collateral-commissural input of rat CA1 neurones was investigated using several inhibitors in vitro. If 10 microM H-8, 100 nM KT5720 or 50 microM Rp-cAMPs was applied to the bath before a triple 100 Hz/0.5 s tetanization, post-tetanic and short-term potentiation developed almost normally. However, from about 3 h after tetanization the long-term potentiation (LTP) of the field-EPSP declined with respect to the control in an irreversible manner. These data suggest that besides protein kinase C the synergistic activation of PKA is necessary for the maintenance of LTP. PMID- 8347814 TI - GABA-responses of CA3 neurones at epileptogenic threshold concentrations of convulsants. AB - Epileptogenic actions of convulsants are often attributed to weakened inhibitory synaptic mechanisms. This assumption was tested by studying GABA-induced postsynaptic membrane potential (MP) changes of CA3 neurones (guinea-pig) before and during exposure to bicuculline methoiodide (BMI), pentylenetetrazol (PTZ), penicillin (PEN) and caffeine (CAF). Under control conditions GABA ejections elicited polyphasic MP fluctuations (components I-III). After adding BMI, PTZ, PEN or CAF, early hyperpolarizations (component I) did not change at epileptogenic threshold concentrations. These convulsants, however, exerted differential effects on the depolarizing component II, but only threshold concentrations of penicillin strongly reduced the amplitude of this component. Simultaneously, component III was slightly accentuated. These findings indicate that changes of GABA responses are not an essential prerequisite for the generation of paroxysmal depolarizations. PMID- 8347815 TI - Electroencephalographic correlates of paced breathing. AB - Multichannel EEG, respiration, blood pressure and ECG were recorded during paced breathing at five frequencies in 18 subjects in order to elucidate the effects of paced breathing on power changes in alpha, beta and theta bands, and on rhythmical variability of these parameters. Mean power in the beta band and low frequency beta power variability (0.12-0.04 Hz) increased during paced breathing at frequencies of 0.25 and 0.20 Hz. The total variability of alpha power in the right parietal and occipital electrodes decreased during paced breathing at 0.1 Hz compared with initial rest. The results point to increased cortical excitability during paced breathing at eupnoeic frequencies and to diminished cortical sensitivity to desynchronizing influences during paced breathing at 0.1 Hz. PMID- 8347816 TI - Avian auditory pathways show met-enkephalin-like immunoreactivity. AB - Pathways associated with a recently defined region of the avian auditory thalamus, the shell of the nucleus ovoidalis (Ov), were examined for met enkephalin immunoreactivity. The presence of enkephalin-like immunoreactive (ELI) perikarya within the medial margin of the inferior colliculus (ICM), afferent to the Ov shell, implicated ICM as a source of ELI fibers within the Ov shell and tract. The shell also contained ELI perikarya and its targets, including the ventromedial hypothalamus and caudoventral paleostriatal complex, were characterized by ELI fields. These data suggest that enkephalinergic auditory pathways, in parallel with traditionally recognized auditory projections, target regions of the avian basal forebrain. PMID- 8347817 TI - Effects of formalin-induced pain on exploratory behaviour in rabbits. AB - We have used formalin to assess the long-term behavioural and hormonal effects of persistent pain in rabbits. Behaviour has been recorded over 10 min sessions both before and after 10 min, 4 and 24 hours after injection of formalin. A low dose of formalin (0.1 ml at 5%) elicited licking of the injected paw which lasted only a few minutes. Exploratory behaviour was greater than in the control (sham injected) animals in all post-injection sessions. Following a larger dose of formalin (0.5 ml at 8%) licking occurred in all post-injection sessions, while exploration was lower than the controls only immediately after injection. Twenty four hours after the formalin injection, testosterone levels were unaffected. Corticosterone levels increased over the course of the experiment but this increase was equal for the experimental and the control groups. Results suggest that different pain intensities and durations have opposite effects on exploratory behaviour in rabbits. PMID- 8347819 TI - Differential activation of c-fos in spinal neurones by distinct classes of noxious stimuli. AB - The laminar distribution of spinal cord neurones expressing immunoreactivity to the Fos protein was evaluated in the rat following chemical, thermal or mechanical noxious stimulation of the skin for 2 h. After stimulation by 20% or 5% formalin, Fos-immunoreactive neurones prevailed in lamina I where they accounted for 64% and 59%, respectively, of the entire population of Fos immunoreactive spinal cells. Values in the remaining laminae were low (2-10%). Following thermal stimulation by radiant heat at 65 degrees C or 58 degrees C, Fos cells were concentrated in laminae I and IIo, amounting to 57% and 62%, respectively, in lamina I, and to 26% and 29% in lamina IIo. Values were lower than 10% in the remaining laminae. Following mechanical stimulation by pinching or needle prick, Fos-positive cells were regularly distributed throughout laminae I-V amounting to 25-26% in lamina I, and 10-20% in each of the remaining laminae. These findings suggest that the spinal neuronal groups upon by prolonged noxious stimulation differ according to the nature of the stimulus. PMID- 8347818 TI - Simultaneous demonstration of central projections of different peripheral nerves by anti-choleragenoid immunoglobulin markers. AB - This study demonstrates a fluorescent antibody technique where immunoglobulins (IgG) can be used as transganglionic tracers for the simultaneous demonstration of different primary afferent nerve projections to the spinal cord. Antiserum against choleragenoid (CTB) raised in goat or rabbit was mixed with CTB to obtain a solution consisting of IgG bound to CTB. The mixtures of rabbit and goat IgG bound to CTB were subsequently injected into the sciatic or femoral nerves. Following transganglionic transport, goat and rabbit IgG staining were demonstrated simultaneously in different areas of the L4 dorsal root ganglion, in the spinal cord and in the brain stem, using an immunocytochemical technique. When only goat anti-CTB antibodies or only CTB were injected into the sciatic nerve, no goat IgG immunoreactivity could be detected in the spinal cord. PMID- 8347820 TI - Cholesterol metabolism and violence: a study of individuals convicted of violent crimes. AB - To examine the relationship between plasma lipoproteins and apolipoproteins in men with convictions for violent offences, blood was obtained from 15 men with a history of violence who were serving prison sentences for violent offences, and 25 age-matched male controls from the staff of the Argyll and Bute Psychiatric Hospital, who had no criminal records. The two groups did not differ in plasma total cholesterol concentrations, HDL-C, LDL-C, VLDL-C or in HDL subfractions. The most significant differences in the offenders were higher apoprotein AIV (3.62 vs 0.85: p = < 0.000001) and higher apoprotein E (7.70 vs 5.19: p = < 0.0002). PMID- 8347821 TI - Plasma amyloid precursor protein is decreased in Alzheimer's disease. AB - Alzheimer's disease is characterized by amyloid deposits whose major protein component is beta A4. beta A4 is a product of the amyloid precursor protein (APP). APP was assayed in partially purified plasma samples from 16 sporadic Alzheimer's disease patients, 12 age-matched controls, 15 Down's syndrome individuals aged 19-36 years and 8 young to middle-aged controls (22-51 years). 14 of the 16 Alzheimer's disease patients had decreased plasma APP when compared with age-matched controls. 14 of the 15 Down's syndrome individuals had similar levels of APP when compared with age-matched and elderly non-demented controls by immunoblotting, whereas one had levels of APP less than controls. Taken together with results from a previous report (Lancet 1992; 340: 453-454), the decreased plasma APP levels mirror the changes observed with cerebrospinal fluid APP levels in Alzheimer's disease. PMID- 8347823 TI - GangliosideGM1 expression during human spinal cord and neural crest development. AB - GangliosideGM1 represents a widespread component of the neural cell plasma membranes. Cholera toxin-B subunit binds selectively to GM1. Human spinal cords at post-conception (PC) weeks 6 to 11 were examined and early GM1 expression shown on the cell plasma membrane in the developing grey matter at PC week 6. GM1 was demonstrated also in the marginal layer (white matter); on neural crest derivative plasma membrane, i.e. dorsal root (DRG) and sympathetic ganglia; along emerging fibres from DRG and neurite terminals innervating skeletal muscle. GangliosideGM1 is highly expressed in spinal cord primary cultures and is a stringent neural cell marker. GangliosideGM1 represents an early marker of neural differentiation in both spinal cord and neural crest derivatives. PMID- 8347822 TI - Immunocytochemical localization of 5-HT1A receptors in the rat immature cerebellum. AB - The serotonin 5-HT1A receptors were visualized in the cerebellar vermis of 8-day old and adult rats by immunocytochemistry using anti-5-HT1A receptor antibodies raised against a synthetic peptide corresponding to a highly selective portion of the receptor amino acid sequence (El Mestikawy et al, Neurosci Lett 118, 189-192, 1990). The 5-HT1A receptor-like immunoreactivity was particularly abundant in the posterior lobules (IXB-X) of the immature vermis where it was found in the molecular-Purkinje cell layers. Immunostaining was confined to the plasmic membrane of the Purkinje cell somas, dendrites and perhaps axons (at their somatic emergence) suggesting that 5-HT receptors might participate in non junctional 5-HT neurotransmission in the immature cerebellum. PMID- 8347824 TI - Phosphorylated MAP1b, alias MAP5 and MAP1x, is involved in axonal growth and neuronal mitosis. AB - Microtubule-associated protein 1b, also named MAP5 and MAP1x, is essential for neuronal differentiation. In kitten cerebellum, this protein is partially phosphorylated. During early postnatal development, a phosphorylated form was localized prominently in growing parallel fibres and in mitotic spindles of neuroblasts in the germinal layer, whereas a non-phosphorylated MAP1b form was found in dendrites, perikarya and axons. The MAP1x epitope showed the same immunohistochemical distribution, as seen for phosphorylated MAP1b, while its recognition on immunoblots was independent of phosphorylation. It is concluded that post-translational modifications and conformation of MAP1b influence the immunological detection of MAP1b, and are essential in the neuronal growth processes and mitosis. The antibody against the phosphorylated MAP1b may represent a good marker to identify dividing neurones. PMID- 8347825 TI - CNTF promotes the survival of neonatal rat corticospinal neurons in vitro. AB - Corticospinal neurons were identified in cell cultures of neonatal rat cortex by immunostaining of cholera toxin B subunit (CTB), retrogradely transported from the cervical part of the spinal cord. The CTB-immunoreactive neurons were larger than the neurons in the overall (unstained) neuronal population and represented a small fraction of it (average of 0.3%) after 6 hours in vitro. The number of both total and CTB-labeled neurons declined progressively with time in culture. The neuronal death was, however, markedly faster in the CTB-labeled neuronal population than in the overall neuronal population. Ciliary neurotrophic factor (CNTF) promoted the survival of CTB-positive corticospinal neurons in a dose dependent manner; with CNTF, the death rate of the CTB-labeled neurons became identical to that of the overall population. PMID- 8347828 TI - Neuronal subpopulations in a reptilian thalamic reticular nucleus. AB - In reptiles, Caiman crocodilus, some neurons in the thalamic reticular nucleus are immunoreactive for parvalbumin. Utilizing double-labeling experiments with fluorescent tracers and indirect fluorescence immunocytochemistry, some of these parvalbumin immunoreactive neurons were found to project to the dorsal thalamus. Other thalamic reticular neurons not immunoreactive for parvalbumin were also found to terminate in the dorsal thalamus. These findings suggest that the thalamic reticular nucleus in Caiman contains at least two chemically, and perhaps functionally, distinct neuronal subpopulations. PMID- 8347826 TI - Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat. AB - The effects of acute and subchronic (7 days) administrations of the adrenocortical hormone corticosterone on basic fibroblast growth factor (bFGF, FGF-2) immunoreactivity were studied in the substantia nigra of the rat by semiquantitative immunocytochemistry coupled with image analysis. Corticosterone was able to increase FGF-2 immunoreactivity in different nigral subregions and cell types (astrocytes and neurones) depending on the duration of the treatment. These results open up the possibility that stress hormones can modulate the trophic state of the substantia nigra through an action on FGF-2. PMID- 8347827 TI - Iron(III) chloride injection increases nigral uric acid in guinea-pig. AB - The present study was carried out to determine if iron chloride (FeCl3) injections into the substantia nigra of guinea-pigs produced changes in nigro striatal uric acid levels. Two-weeks following unilateral injection of FeCl3 (185 nmol Fe3+), ipsilateral uric acid levels were increased 176% over contralateral levels in the substantia nigra. No effect on striatal uric acid levels was observed. Iron chloride injection produced a 74% depletion of dopamine levels in the ipsilateral striatum. Ipsilateral/contralateral ratios were significantly decreased for striatal dopamine and significantly increased for nigral uric acid when compared with saline-injected controls. The results of this work indicate that FeCl3 injections into the substantia nigra of guinea-pigs produce a significant, localized increase in tissue uric acid levels two weeks after treatment. PMID- 8347829 TI - A mitochondrial DNA deletion in normally aging and in Alzheimer brain tissue. AB - By quantitative polymerase chain reaction (PCR) of total cellular DNA, the known 4977 bp deletion in human mitochondrial DNA (mtDNA delta 4977) was not detected in rapidly dividing tissue such as placenta and lymphocytes, nor in brain tissue from fetuses and in frontal cortex from two individuals 24 and 56 years old. However, in frontal cortex from individuals 71-95 years 0.13% deleted/undeleted mtDNA was found, with no significant difference between Alzheimer patients (0.14%) and age-matched controls (0.12%). We hypothesize that the age-related accumulation of this deletion (and other expected deletions) contributes to the down-regulation of adenosine triphosphate (ATP) production in neurons and other non-dividing cells, a fundamental mechanism common to aging and Alzheimer's disease. PMID- 8347830 TI - Cellular localization of hydroxyindole-O-methyltransferase mRNA in the chicken pineal gland. AB - Hydroxyindole-O-methyltransferase (HIOMT), is the last enzyme of the melatonin biosynthesis pathway. We have applied immunocytochemistry and in situ hybridization to localize HIOMT producing cells, in the chicken epithalamus including the pineal gland. The selectivity of the hybridization signal over melatoninergic cells was ascertained by comparison with the immunolabelling. HIOMT transcripts could be observed in the two cell layers of the pineal follicles and in the pineal stalk, but not in other epithalamic regions. These results indicate that pineal modified photoreceptors and parafollicular pinealocyte-like cells represent the two populations of melatonin-producing cells of the chicken epithalamus. PMID- 8347831 TI - Induction of beta-amyloid precursor protein isoform mRNAs by bFGF in astrocytes. AB - All three major transcripts of beta-amyloid precursor protein (APP) were expressed in astrocytes. The ratio for APP695, APP751 and APP770 isoform mRNAs being 1:4:2. Treatment with bFGF and EGF produced upregulation of APP mRNAs in cultured astrocytes in varying proportions. In comparison with controls, increases in APP mRNAs in bFGF and EGF treated groups were about 4.5 and 2 fold, respectively. The elevation in mRNAs of KPI-containing isoforms APP751 and APP770 was relatively more than the elevation in mRNA of APP695 isoform. Our findings provide further evidence for the involvement of astrocytes in a cascade of events leading to the development of senile plaques in Alzheimer's disease and Down's syndrome. PMID- 8347833 TI - Modulation of epithelial morphogenesis and cell fate by cell-to-cell signals and regulated cell adhesion. AB - Cell-cell and cell-extracellular matrix (ECM) interactions control many developmental decisions of epithelial cell fate and morphogenesis. Protein tyrosine kinases are one class of regulatory molecules that have been implicated in the modulation of these processes. Several protein tyrosine kinases co localize with cell-cell (cadherin) and cell-ECM (integrin) adhesion molecules at specific adhesion domains of epithelial cells. Protein tyrosine kinases may regulate epithelial development by modulating cell-cell and cell-ECM interactions and by relaying signals initiated by these interactions to other cellular components that determine cell structure and function. PMID- 8347832 TI - Compensation of a sensory deficit inflicted upon newborn and adult animals. A behavioural study. AB - Somatosensory deprivation (bilateral vibrissa clipping) was performed on newborn (P1) and adult (P80) rats and, on 10 successive days starting on day 81, the effect of sensory deprivation was tested in a rectangular maze versus controls. The maze performance (the time to reach the goal-box with food reward) of the P80 animals was significantly poorer than that of P1 animals. The tests repeatedly demonstrated, however, that the maze performance achieved by the P1 animals was better than that of the controls. This behavioural study clearly revealed that early sensory deprivation induced (probably cross-modal) compensatory changes in other sensory systems. PMID- 8347834 TI - Transmembrane control of cadherin-mediated cell-cell adhesion. AB - The cadherin family of cell-cell adhesion molecules plays a central role in organization of cells into multicellular structures. An important feature of the action of cadherins is that they form a complex with cytoskeletal proteins, and the formation of this complex is crucial for their adhesive function. Cadherin mediated cell adhesion is thus controlled through the interaction with cytoplasmic proteins, and, for such control, phosphorylation of these proteins and also cadherins themselves might be involved. This regulatory mechanism of cell adhesion is perhaps fundamental to a variety of morphogenetic processes. PMID- 8347835 TI - Human cytotrophoblast invasion. AB - During early pregnancy, fetal chorionic villi that contact the uterine wall give rise to columns of mononuclear cytotrophoblasts that penetrate the superficial portion of the uterus. From these columns emanate cytotrophoblasts that invade deeply into the uterus and its arterioles. To investigate the molecular basis of this unusual, regulated invasive behavior, we used a combination of approaches that included an in vitro model of cytotrophoblast invasion and immunocytochemistry on uterine biopsy sections containing invading cytotrophoblasts. Our results showed interesting roles for: matrix-degrading metalloproteinases, adhesion receptors and their extracellular matrix ligands, and the class I molecule HLA-G. PMID- 8347836 TI - Extracellular matrix and gene expression in mammary epithelium. AB - Correct cellular environment is required for the differentiation of many cell types. In mammary epithelium the extracellular matrix as well as lactogenic hormones cooperate to direct accurate tissue-specific gene expression. Current evidence indicates that the promoters of milk protein genes contain elements that are regulated by both extracellular matrix and hormones. Some mechanisms by which the extracellular matrix might control transcription are considered. PMID- 8347837 TI - How to build a kidney. AB - Embryonic kidney is ideal for the study of epithelial morphogenesis--rich in developmental processes, accessible and clinically important. Interactions between mesenchyme and the epithelium invading it cause the epithelium to differentiate and branch to form the collecting ducts, and the mesenchyme to epithelialise into excretory nephrons. Molecular analyses reveal complex programmes of expression of transcription factors and morphoregulatory molecules, correlating with induction and morphogenesis. In developing nephrons especially, the detailed timing of this programme is now being explored and the functions of some molecules involved have been tested by inhibition experiments. New pharmacological methods of induction may also prove useful in solution of the mechanisms by which a kidney is formed. PMID- 8347838 TI - Heterotypic cellular cooperation in gut morphogenesis and differentiation. AB - The development of the gastrointestinal tract, like that of other organs, results from the association of intrinsic genetic endowment, endogenous regulatory mechanisms and environmental influences. The present chapter emphasizes the role of epithelial-mesenchymal interactions during development and crypt-villus migration. Arguments are given as to the role of basement membrane molecules as mediators for these cell interactions. Differential developmental expression of the various extracellular matrix components, which precedes the onset of differentiation markers, suggests that each of these molecules assumes a specific task. Yet, much work still remains to be done before knowing exactly how transfer of morphogenetic signals between epithelial and mesenchymal tissues occurs. PMID- 8347839 TI - Inter-organ communication between intestine and liver in vivo and in vitro. AB - The maintenance of body homeostasis requires a finely tuned system of interorgan communication. The intimate metabolic interrelation between intestine and liver is characterized by the unique anatomic position of both tissues using the portal vein as a private channel with the pancreas in optimal position to modulate hepatic metabolism. Gut-derived peptides (such as glucagon-like peptide-1) appear to be involved in the process of liver regeneration by regulating the release of pancreatic hormones (e.g. insulin). Extensive bowel resection or functional exclusion of small intestine may lead to severe liver dysfunction and even cirrhosis, which may be due to the lack of some intestine-derived and as yet unknown factor(s). Here a close cooperation between small intestinal mucosa and hepatocytes is demonstrated leading to the concept of a metabolic gut-liver unit. This metabolic interaction forms a wide spectrum ranging from the secretion of peptide hormones to changes in (portal-venous) substrate availability or hepatocyte cell volume. Further investigation and identification of the mechanisms of such regulatory processes may be facilitated by combined perfusion of isolated rat intestine and liver. Using this in vitro approach we could demonstrate the presence of metabolic interorgan communication between isolated perfused tissues independent of plasma borne hormones or extrinsic neural control. PMID- 8347840 TI - The acute retroviral syndrome and the pathogenesis of HIV-1 infection. AB - The acute retroviral syndrome associated with primary HIV-1 infection is characterized by clinical signs of immune activation, multi-system dysfunction, and high levels of cell-associated and plasma viremia, p24 antigenemia, and proviral burden. Clinical abnormalities associated with acute HIV-1 infection and measures of viral burden and replication generally decline in concert with seroconversion. Despite clearance of virus, patients experiencing severe forms of the acute retroviral syndrome appear to have a poorer prognosis than patients with asymptomatic primary infection. This accelerated natural history may be due to the virulence of strains causing symptomatic infection, sequelae of initial high-titer viremia and consequent high viral burden, or immune depletion through immunopathologic mechanisms accelerated by strong antigenic stimulus in primary infection. Early intervention with anti-retroviral and immune modulatory agents has the potential to alter the natural history of patients with this syndrome. PMID- 8347841 TI - The immune response to HIV: implications for vaccine development. AB - HIV infection is accompanied by a vigorous immune response to the virus consisting of humoral and cellular elements that effectively neutralize virus infectivity and lyse infected cells when analyzed in cell culture models. However, this immune response shows no evidence of being able to eliminate the infection. The inability to clear this infection places HIV in a category of viruses for which vaccines have yet to be successfully developed. Indeed, effective vaccines have emerged only for viruses where natural immunity is part of the pathogenic process; it is such immunity that became the guiding principle for the development of the respective vaccines. It follows that the unique features of HIV infection and pathogenesis are issues to consider carefully in formulating vaccine strategies, particularly those that relate to its susceptibility to immune attack on the one hand, and its mechanisms of immune escape on the other. PMID- 8347842 TI - Breast cancer surveillance--a cost-effective strategy. AB - The effectiveness of a surveillance program for breast cancer recurrence in extending survival is predicated on two assumptions: 1) most recurrences are detected at an early stage at surveillance visits; and 2) the early treatment of recurrence offers a better chance of cure or longer survival. However, the data suggest that neither of these two assumptions is correct, and that postoperative follow-up of patients with breast cancer is expensive and does not significantly extend survival. PMID- 8347843 TI - Cost-effectiveness of breast cancer screening: preliminary results of a systematic review of the literature. AB - There is now considerable concern that universal access to health care within realistic resource constraints requires some sort of cost-effectiveness analysis of given medical procedures and interventions. One such intervention is routine mammographic screening for breast cancer. Here, we report preliminary results from an ongoing project to conduct a systematic and comprehensive review and comparison of the published cost-effectiveness analyses of screening for the early detection of breast cancer. We examine 16 such studies, and compare two studies in detail to explain how differences in assumptions and in consideration of down-stream effects have caused the published results for apparently comparable breast cancer screening programs to span a broad range. PMID- 8347844 TI - Payment and coverage issues affecting medical oncology. AB - Medical oncologists continue to face significant issues in obtaining full payment for and coverage of their services by third-party payers. A number of issues raised by the Medicare fee schedule have, however, been at least partially resolved in a favorable manner. There continue to be problems in coverage of off label drug uses and services associated with clinical trials. The impending reform of the health care system may improve the situation or it may give rise to further difficulties. PMID- 8347846 TI - Human recombinant interferon-beta SER and tamoxifen: growth suppressive effects for the human breast carcinoma MCF-7 grown in the athymic mouse. AB - Tamoxifen is the endocrine treatment of choice for breast cancer. However, resistance to therapy and patient relapse inevitably occurs. In future treatment schedules, interferons could be administered with tamoxifen, in an attempt to prevent disease recurrence. Human recombinant interferon-beta SER (rIFN-beta SER) inhibited the growth in vitro of the estrogen receptor (ER) positive breast cancer cell line MCF-7 and the ER negative breast cancer cell line MDA-MB-231. This inhibitory effect was achieved at doses of 50 U/ml and above. The growth of MCF-7 tumors in estradiol-stimulated athymic mice was greatly inhibited by high dose rIFN-beta SER treatment (10(6)U/day). In spite of the impressive antitumor effects upon MCF-7 tumors, rIFN-beta SER had no effect upon ER levels within the tumors at either the RNA or protein level, as measured by Northern blotting and ER-EIA respectively. High dose rIFN-beta SER (10(6)U/day) did result in some inhibition in the growth in vivo of the tamoxifen-stimulated MCF-7 variant MCF-7 TAM, although not to the same extent as was observed with the estradiol stimulated MCF-7 tumors. rIFN-beta SER was also administered to animals bearing MCF-7 tumors and treated with estradiol and tamoxifen. In the animals undergoing high dose therapy (10(6)U/day), tumor growth was completely suppressed. Furthermore, tumor growth continued to be suppressed in those animals in which the rIFN-beta SER therapy was halted and the tamoxifen capsule removed. No tumors were observed in spite of the environment of estradiol stimulation. Thus, the combination of interferon and tamoxifen was totally growth suppressive for MCF-7 xenografts in nude mice. PMID- 8347845 TI - Predicting recurrence in axillary-node negative breast cancer patients. AB - This study attempted to identify the risk groups in axillary node negative breast cancer patients using validated first-generation prognostic clinical and pathologic factors. An updated 10-year follow-up in 407 such patients treated by surgery alone at Roswell Park between 1976-1987 showed a 10-year recurrence rate (RR) of 19% (95% confidence interval +/- 5%). Predictors of outcome were, in order of strength: (1) Tumor size (p = 0.0006); RR at 10 years was 2% +/- 4 for tumors < or = 0.5 cm, 6% +/- 7 for tumors 0.6-1.0 cm, 16% +/- 9 for 1.1-2 cm, 29% +/- 12 for 2.1-5 cm, and 40% +/- 31 over 5 cm; (2) Histologic differentiation (p = 0.017); poorly differentiated/anaplastic (P/A) tumors had a greater RR (24% +/- 8) than well or moderately differentiated (W/M) tumors (13% +/- 8); (3) Age (p = 0.046); patients < 35 showed a RR of 28% +/- 20, pts 35-50, 22% +/- 10, and pts > 50,17% +/- 7 (p = 0.046). Cox Model analysis showed tumor size (4 groups) significant at < 0.0001, histologic differentiation (2 groups) significant at < 0.0005 after allowing for size, and age (+/- 50) significant at < 0.05 after allowing for size and differentiation. Combining these variables into subgroups enables selecting groups at various risks of recurrence. Groups with low risk are: (1) patients with tumor < or = 1 cm, W/M (0% RR), (2) patients with ductal carcinoma in situ with microinvasion (0% RR), and (3) patients with tumors < or = 1 cm, P/A (8% RR). In a suggestive finding in this last group, those over age 50 achieved a RR of 3% +/- 6, while those age 50 or less had RR 14% +/- 15. With the exception of this last group, all should be considered highly curable using loco regional therapy alone, and might be spared the risks and costs of routine systemic adjuvant therapy. Groups with high risk are: (1) patients with tumors > 2 cm (RR 32% +/- 12), and (2) patients with tumors 1.1-2 cm, P/A (RR 21% +/- 14). These should receive adjuvant therapy. Groups with intermediate risk are patients with tumor 1.1-2 cm, W/M (RR 12% +/- 12). In a suggestive finding, those in this group over age 50 had a RR of 11% +/- 12, while those up to 50 had a RR of 17% +/ 30. These patients should be considered to be prime candidates for clinical trials.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8347848 TI - Candidate metastasis-associated genes of the rat 13762NF mammary adenocarcinoma. AB - Differential hybridization was used to isolate genes potentially involved in the process of metastasis. Ten complementary DNAs (cDNAs) that were differentially expressed between a highly metastatic (MTLn3) and a nonmetastatic (MTC.4) line of the rat 13762NF mammary adenocarcinoma were isolated and sequenced. Examination of the EMBL/GenBank database revealed that one of the genes had a high degree of homology (98.8%) to annexin I (also known as calpactin II). Quantitative analysis of Northern blot hybridizations showed that the annexin I-like sequence was expressed 4- to 7-fold higher in MTLn3 than in MTC.4 cells. Steady state mRNA levels were also low in MTLn2, a cell line of low metastatic potential closely related to MTLn3, but were not related to metastatic potential in colon adenocarcinoma or melanoma cells. Two of the cDNAs (designated 8.11 and 10.14) were found to be novel. The expression of 10.14 mRNA (3.2 kb) was 4-fold higher in MTLn3 than in MTC.4 cells. Sequencing of the 10.14 cDNA (2.2 kb) revealed a putative open reading frame of 583 amino acids that was also novel. Expression of 8.11 mRNA (> 7 kb) inversely correlated with metastatic potential. Another differentially transcribed gene was highly homologous to ERK2 (extracellular signal related kinase 2), a mitogen-activated protein kinase (MAPK). Northern analysis of ERK2 expression revealed 3-fold higher amounts of a 1.3 kb mRNA in MTLn3 than in MTC.4 cells. Higher levels of ERK2 mRNA were generally seen in the more metastatic human colon but not in melanoma cell lines. We also corroborated the work of Taniguchi (Nucl Acids Res 19:6949, 1991) by independently identifying EF-1 alpha as a putative metastasis-associated gene. PMID- 8347850 TI - Assessing the cost effectiveness of adjuvant therapies in early breast cancer using a decision analysis model. AB - BACKGROUND: We have developed a decision analysis model that uses the results of available randomized controlled trials to model the natural history of early breast cancer and assess the potential clinical and financial effects of using adjuvant therapies. PATIENTS AND METHODS: The original model was used to assess the impact of chemotherapy in hypothetical groups of 45-year-old and 60-year-old node-negative, estrogen receptor-negative women. Using the 1992 Early Breast Cancer Trialists' Collaborative Group report, we have expanded and revised the model to assess: 1) the role of tamoxifen alone, chemotherapy alone, or combined therapy in pre-menopausal women, and 2) chemotherapy in elderly women with node negative, estrogen receptor-negative cancer. RESULTS: For pre-menopausal women, we found that chemotherapy increases quality adjusted life expectancy and survival by a substantial amount at a cost less than most accepted medical interventions. Combined therapy is beneficial and cost-effective in estrogen receptor-positive cancer. For the elderly, chemotherapy prolongs survival but to a lesser extent compared to younger women. The cost of this benefit is high but within the range of commonly reimbursed procedures for women under age 75 without other co-existing conditions. CONCLUSIONS: For most patients some form of adjuvant therapy is beneficial and cost-effective. The model builds upon the data derived from collaborative efforts assessing the effectiveness of adjuvant therapies. The model highlights the need for an equal commitment to assessing the economic and quality of life impacts of breast cancer treatments. PMID- 8347851 TI - Role of granulocyte-macrophage colony stimulating factor (GM-CSF) after autologous bone marrow transplantation for Hodgkin's disease. AB - Use of growth factors to augment hematopoietic recovery after cytotoxic therapy is a useful method for dose intensification. We wanted to evaluate the clinical and cost-effectiveness of granulocyte-macrophage colony stimulating factor (GM CSF; Leucomax) in patients undergoing autologous bone marrow transplantation (ABMT) for Hodgkin's disease. Twenty-four patients with Hodgkin's disease were treated with high-dose chemotherapy and ABMT. Patients were then randomized in a double-blind manner to receive GM-CSF intravenously (10 micrograms/kg) over 6 h or placebo until the absolute neutrophil count (ANC) was greater than 1000/mm3 for 3 days. The study medication was stopped after 30 days. Patients treated with GM-CSF (n = 12) had shorter periods of neutropenia (median duration of an ANC of less than 1000 cells/mm3, 16 versus 27 days on placebo; p = 0.23), shorter periods of platelet-transfusion dependency (median duration, 13.5 versus 21 days on placebo; p = 0.03), shorter hospitalizations (median hospital stay, 32 versus 40.5 days on placebo; p = 0.0004). Other clinical outcomes, such as frequency and severity of toxicities, development of pneumonia or infection, in-hospital death, and response rate were similar in the two groups. Actuarial long-term disease free survival was 58% for patients treated with GM-CSF and 50% for patients who received placebo after 38 months of follow up (p = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347849 TI - Nm23 and breast cancer metastasis. AB - The majority of breast cancer patients succumb to metastatic disease. We summarize published and recent research concerning the nm23 gene in breast cancer metastasis. In a murine developmental study, nm23 expression increased with the functional differentiation of the mammary gland in nulliparous and pregnant animals. In human breast cancer, five studies have now demonstrated a significant association between reduced nm23 expression, at the RNA or protein levels, and aggressive tumor behavior. Nm23-negative tumor cells have been observed in comedo ductal carcinoma in situ lesions in two independent studies, indicating that decreases in nm23 expression begin prior to actual histologically identifiable invasion. Transfection studies, in which human nm23-H1 cDNA was expressed in the metastatic human MDA-MB-435 breast carcinoma cell line, indicate that nm23-H1 suppresses in vivo metastatic potential by 50-90%. Finally, our data in melanoma and breast carcinoma transfection systems suggest that the biochemical mechanism of nm23 suppressive activity is likely not due to its nucleoside diphosphate kinase activity, association with GAP proteins, or secretion from cells. PMID- 8347847 TI - Mechanisms involved in the metastasis of cancer to bone. AB - The metastasis of cancer to bone is a frequent outcome of common malignancies and is often associated with significant morbidity due to osteolysis. Bone metastasis is also selective in that a disproportionately small number of malignancies account for the majority of tumors which spread to bone. While the mechanisms of bone destruction have been studied, those responsible for the site-specific nature of bone metastasis are poorly understood. As a metastatic target, bone is unique in that it is continuously being remodelled under the influence of local and systemic growth factors, many of which are embedded in the bone matrix. This review summarizes evidence for the hypothesis that the formation of metastatic tumors in bone is the consequence of a unique microenvironment where metastatic cells can alter the metabolism of bone, thereby regulating the release of soluble bone-derived growth factors as a consequence of bone resorption. These, in turn, can modulate the malignant phenotypic properties of receptive cells. Transforming growth factor-beta is one factor which can promote the growth and motility of Walker 256 cells, a rat cell line with a propensity to metastasize spontaneously to bone. PMID- 8347853 TI - First experiences and perspectives for the use of cytokines in the treatment of non-Hodgkin's lymphoma. AB - Numerous clinical trials have been carried out to investigate the therapeutic potential of cytokines in the management of non-Hodgkin's lymphoma (NHL). Relevant interferon-alpha activity is restricted to low-grade malignant NHL of both B and T cell subtypes, provided the tumor mass is low. Granulocyte macrophage colony stimulating factor (GM-CSF) accelerates hematopoietic recovery following myelosuppressive therapy, and reduces the risk and severity of infection. Thus, GM-CSF support makes does intensification feasible and may thereby contribute to an improvement of response rates and long-term survival. Among interleukins (IL) studied, IL-2, with or without lymphocyte activated killer cells, so far has only achieved stabilization of refractory NHL but this approach may still require further refinement. IL-3 has already been successfully applied in the treatment of NHL, augmenting neutrophil and platelet recovery after conventional salvage therapy or following autologous bone marrow transplantation. On the basis of these findings promising applications for the use of cytokines in the treatment of NHL can be envisaged. PMID- 8347852 TI - Granulocyte-macrophage colony stimulating factor (GM-CSF) in the treatment of hematological malignancies. AB - Acute myeloid leukemic (AML) cells not only express receptors for various cytokines but also produce hemopoietic growth factors themselves. Thus, they are able to stimulate their own activation and proliferation, a phenomenon known as autocrine growth. The cell cycle kinetics of AML blast cells are susceptible to stimulation by a variety of cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-3, granulocyte colony stimulating factor and stem cell factor. GM-CSF and IL-3 can markedly enhance the cytotoxicity of chemotherapeutic agents by increasing the proportion of AML cells in S-phase at any given time and by altering the metabolic status of the AML cells. A number of clinical studies involving the use of GM-CSF in association with chemotherapy in patients with AML are currently ongoing. In the next few years the first clinical results will become available indicating whether the use of cytokines holds any benefit for patients with AML. PMID- 8347854 TI - Future outlook for growth factors. AB - In the future improvements in the efficacy and safety profiles of the various growth factors in clinical use should be achievable through optimization of dosage schedules. The use of combinations of growth factors to provide hemopoietic support should enable considerable advances to be made in the treatment of hematological and non-hematological malignancies. Growth factors, such as granulocyte-macrophage colony stimulating factor may be used not only to maximize neutrophil recovery after myeloablative therapy, but also to mobilize peripheral blood stem cells prior to harvesting by leukapheresis. Growth inhibitory cytokines such as transforming growth factor-beta and macrophage inflammatory protein-1 alpha may be used to protect normal cells in the bone marrow and other sites where dose-limiting toxicities occur. Therefore, in the next few years, the whole approach to chemoradiotherapy will need to be reconsidered in the light of the dose intensification made possible by improved bone marrow support techniques and advances in other areas of supportive care. PMID- 8347855 TI - The molecular control of hematopoiesis. AB - Experiments both in vitro and in vivo have increased our understanding of how cytokines can act to influence the maintenance of the primitive hemopoietic populations and the production of mature blood cells. Such understanding helps us to use cytokines as therapeutic agents in order to manipulate the hemopoietic response to disease and its treatment. PMID- 8347856 TI - Proteolytic processing of the vitellogenin precursor in the boll weevil, Anthonomus grandis. AB - The soluble proteins of the eggs of the coleopteran insect Anthonomus grandis Boheman, the cotton boll weevil, consist almost entirely of two vitellin types with M(r)s of 160,000 and 47,000. We sequenced their N-terminal ends and one internal cyanogen bromide fragment of the large vitellin and compared these sequences with the deduced amino acid sequence from the vitellogenin gene. The results suggest that both the boll weevil vitellin proteins are products of the proteolytic cleavage of a single precursor protein. The smaller 47,000 M(r) vitellin protein is derived from the N-terminal portion of the precursor adjacent to an 18 amino acid signal peptide. The cleavage site between the large and small vitellins at amino acid 362 is adjacent to a pentapeptide sequence containing two pairs of arginine residues. Comparison of the boll weevil sequences with limited known sequences from the single 180,000 M(r) honey bee protein show that the honey bee vitellin N-terminal exhibits sequence homology to the N-terminal of the 47,000 M(r) boll weevil vitellin. Treatment of the vitellins with an N glycosidase results in a decrease in molecular weight of both proteins, from 47,000 to 39,000 and from 160,000 to 145,000, indicating that about 10-15% of the molecular weight of each vitellin consists of N-linked carbohydrate. The molecular weight of the deglycosylated large vitellin is smaller than that predicted from the gene sequence, indicating possible further proteolytic processing at the C-terminal of that protein. PMID- 8347858 TI - [Current and future perspectives of medical information network systems for community health using personal computers and IC cards]. AB - Recent developments in computer and communication technology were studied in relation to medical information network systems, using computers and IC cards, to solve problems in community health. Trial use of personal computer network systems among physicians and IC card systems for personal health data management are already in existence in some parts of Japan. These trials were studied and analyzed based on a questionnaire survey of physicians and patients. Results of the study produced some useful points that should be considered when introducing these systems. These included: 1) details on expectations and specifications for these systems by physicians and patients, 2) easy access to valuable information is a key point for active network systems among physicians, 3) plausibility of improvement of communication between physicians and patients by using these systems, 4) recognition that an important problem concerns patient information privacy and must be considered before introducing these systems. A study of practical merits of these systems and methodology for realization indicates that participation by active and attractive providers of information can be expected to stimulate frequent use of the network system. The cost of introducing these systems can be partially borne by eliminating the large investment now allocated for processing requests for reimbursement of medical services. Investigation into the introduction of medical information systems provides a good opportunity to elucidate problems in the present medical systems. PMID- 8347857 TI - Comparison of two juvenile hormone radioimmunoassays. AB - Juvenile hormone from the hemolymph of adult worker honey bees of known age and behavioral status was extracted and analyzed by two different radioimmunoassays in two independent laboratories. The assays are different in hapten attachment, radiolabeled tracer, and the method by which bound and unbound hormone are separated. Despite these differences in the methods, hormone determinations were in excellent agreement at lower levels (0-50 ng/ml) but diverged as the hormone concentrations increased (> 50 ng/ml). The relative changes are in good agreement, with a correlation coefficient of 0.97. PMID- 8347859 TI - [Effectiveness of a nutritional education program in lowering blood cholesterol levels in a public health center]. AB - An educational program for persons found to have high blood cholesterol during health examinations at the Nerima Public Health Center was begun in April, 1989. This program was differed from the usual program in two areas. First, new educational material was developed consisting of a check list of 30 items to assess eating patterns. By checking these items, participants could gain an understanding of what they should change in their eating behavior. Secondly, the table of restricted foods was not used. Participants were advised to achieve healthy eating patterns and followed up with a nutritional consultation that was held after three months, at which time they were interviewed regarding compliance and had their blood cholesterol levels measured. The effectiveness of the new educational program and the relationship between achievement of healthy eating patterns and reduction in blood cholesterol levels were analyzed. The main results were as follows: 1) In subjects (n = 79) who received the new education program in 1989-1990, serum cholesterol levels showed significant reduction, as compared with controls (n = 38) who received the usual education program in 1988 1989. 2) Subjects were divided into three groups according to their changes in serum cholesterol levels,--normalized, improved and unimproved--and the number of items complied with were counted for analysis. The mean score of compliance was highest in the normalized group with significant difference between the normalized and the unimproved groups. 3) The items of the high compliance score in the normalized group were in order of high score "to decrease high-fat meats", "to decrease cakes", "to choose lean meats and poultry without skin" and "to eat vegetables at every meal". PMID- 8347860 TI - [A cross-sectional study on relationships between daily physical activity and concentration of serum cholesterol and body mass index in fifth grade elementary schoolchildren and their parents]. AB - The purpose of this study was to estimate the effects of daily physical activity on serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), body mass index (BMI) and atherogenic index (AI) in 240 fifth grade schoolchildren, their 174 fathers and 212 mothers. Information on daily physical activity was obtained by inquiry with a questionnaire and was also measured directly with a device sensing acceleration of physical movement. In schoolchildren, effect of physical activity on TC, HDL-C and AI was not apparent, but that on BMI was shown. In adult men, HDL-C differed by job classification and increased as the degree of physical labor increased from desk work to light and heavy work. Strength of physical activity using the quotient of total amount of measured physical activity divided by body weight had a significant positive correlation with serum HDL-C (r = 0.20, p < 0.05) and significant negative correlation with AI (r = -0.18, p < 0.05) in adult men. In adult women, daily physical activity did not have a significant correlation to TC, HDL-C, AI or BMI. These results appear to suggest that the effect of daily physical activity on serum cholesterol, AI, BMI of schoolchildren and adult women was smaller than that for adult men. PMID- 8347861 TI - [Effects of 12wk-exercise walking on serum lipids, lipoproteins and apolipoproteins in middle aged women--does menopause status influence training effects?]. AB - The present study examined the effects of 12wk-exercise walking on serum lipids in pre- and post-menopausal women, to elucidate the influence of menopausal status on the training effects. Twenty one premenopausal women (42.2 +/- 5.6 yr) and seventeen postmenopausal women (56.7 +/- 6.9 yr) participated in a 12 wk walking program. Self-monitored exercise walking was performed 3 or 4 times per week in sessions of 45 minutes. Average intensity of the exercise was 57% HRmax in the premenopausal group (Pre-M) and 65.5% HRmax in the postmenopausal group (Post-M), respectively. After adjustment for age, baseline value of apolipoprotein AI (Apo AI) was significantly lower and total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) were higher in Post-M than in Pre-M. After 12 weeks, percent body fat decreased significantly in both groups and BMI decreased in Pre-M. Physical fitness tended to increase only in Pre-M. The increase of high density lipoprotein cholesterol (HDLC) and the decrease of Apo AI, Apo B, TC/HDLC were significant in both groups. The decrease of TC, LDLC, Apo B and TG and the increase of HDLC were common changes in both groups, even after adjusting for baseline values, change in body composition, exercise intensity and total exercise time. Change volume of TG tended to be larger in Pre-M than in Post-M. Results of multiple regression analysis showed that the change in serum lipids, especially cholesterol, correlated to initial values, change in body composition and change in fitness, in Post-M but not in Pre-M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347862 TI - [Functional capacity of the elderly: measurement by the TMIG Index of Competence]. AB - The functional capacity of the elderly was assessed in a national representative sample of elderly community residents. A stratified multistage random sampling yielded, 2,240 eligible persons, and 80.8% of them (n = 1,810) were successfully interviewed. The respondents ranged in age from 65 to 96 years, and the average age was 72.5 years; 43.2% of them were men, and the remaining 56.8% were women. The TMIG Index of Competence, a standardized multidimensional 13-item index of competence, was used for measuring the functional capacity. The total score of the index (maximum 13 points) showed a negatively skewed leptokurtic distribution: 69.6% of the respondents scored 11 points or greater while the mean was 10.8 points. A multiple classification analysis of the total score utilizing age, gender, educational attainment, and size of community as independent variables showed significant effects of age and educational attainment; the score significantly decreased with age, and the highly educated elderly showed higher score than those with lower educational attainment. The results of this study show that the majority of the elderly living in the community are well in functional capacity though the capacity tends to decline with age. The distribution of total scores observed in this study can be considered as a national standard of distribution of functional capacity measured by the TMIG Index Competence. PMID- 8347863 TI - [Estimations of organ dose and health risk of the mass chest X-ray examinations in children]. AB - In Japan, mass chest X-ray examinations are mandated by law for schoolchildren and students. Recently, questions of the justification of such X-ray examination have arisen. In this study the absorbed doses of each organ, and the health detriments from the mass chest X-ray examinations to schoolchildren and students were estimated. The doses of organs were measured by the TLDs (Mg2SiO4), slab phantom, and anthropomorphic phantom. The probability of fatal cancer, and the resultant reduction in life expectancy induced by mass chest X-ray examinations were calculated by the multiplicative risk projection model of the ICRP-1990. The absorbed doses of lung, thyroid glands, esophagus, stomach, breast, and red bone marrow in first-year elementary schoolchildren were 90, 30, 90, 60, 90, and 30 muGy, respectively, and the doses in ovaries and testes were almost nil. Each organ dose of first-year students of junior high school was about 1.5 times that for elementary schoolchildren. The total radiation-induced lifetime cancer risk of schoolchildren and students was from 0.3 x 10(-5) to 0.9 x 10(-5) per person by the multiplicative risk projection model of the ICRP-1990 and a factor of 2 for the DDREF (dose and dose rate effectiveness factor). The reduction in life expectancy by radiation induced fatal cancer was from 15 x 10(-5) years to 50 x 10(-5) years per person. The results of this study suggest that subjects of mass chest X-ray examinations should be carefully selected from the viewpoint of radiation protection. PMID- 8347864 TI - [The effect of Habu toxoid--from the view point of public health center]. AB - In order to clarify the effect of Habu Toxoid, serum sampling was performed with from July 1990 to February 1991, on 503 vaccinated subjects living in Amami Islands by staff of Naze health center. Sera were analyzed by Enzyme Linked Immunosorbent Assay (ELISA) for levels of serum antitoxin to venom, both anti Hemorrhagic Factor 1 (anti-HR1) and anti-Hemorrhagic Factor 2 (anti-HR2). Information on vaccinated subjects-age, sex, occupation, vaccination date, frequency, period and interval of vaccinations, years after final vaccination and past history of Habu bites-was obtained and analyzed with relation to serum antitoxin levels. The following results were obtained: 1) Serum antitoxin levels, both anti-HR1 and anti-HR2, of the Habu bitten group (N = 47) were significantly higher than that of the unbitten group (N = 456). This finding suggests that crude Habu venom injected by bites elevated the levels. Regardless of past history of Habu bites, levels of antibody to HR2 was significantly lower than that to HR1. 2) Among the unbitten group, detection of antitoxin was related to subjects' attributes. Production of antitoxin was related to being male, high frequency of vaccinations, long period of vaccinations and short period after final vaccination. 3) Among the unbitten group, anti-HR2 was found in high levels with the following factors: high frequency of vaccinations and short period after final vaccination. However among the well-vaccinated group (N = 153), differences in antitoxin levels by vaccination frequency were not recognized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347865 TI - [Investigations on the quality of well water in the Sakata-Akumi areas of Yamagata-ken]. AB - Samples of well-waters were collected from 1988 through 1992 from 40 shallow wells (non-confined ground water), with samples taken from the well at 16 m depth from the ground surface up to the bottom of the well. Wells were located in the Sakata Akumi area of Yamagata-ken. The water quality was analyzed for 29 items and the results are as follows: 1) In the rural area on the coast of the Sea of Japan, the soil consists of sand, mud and gravel, and dry field farming with cultivation of fruit and vegetables is carried on. Concentrations of nitrate and nitrite nitrogen (NO2+3-N) in the well waters (n = 12) in this area were found to be in the range of 2.3-19 mg/l with the average of 8.2 mg/l, probably mainly derived from agriculture. On the other hand, in the rural area where the indigenous rock consists mainly of andesite and basalt and where rice crops are cultivated, the concentrations of NO2+3-N in the well water (n = 21) were found in the range of 0.15-2.9 mg/l with the average of 0.69 mg/l. 2) The concentrations of NO2+3-N were analyzed monthly for a total of 20 times between 1991 to 1992, from the Sea of Japan coastal region where the highest average of 19 mg/l from all samples was obtained. Analysis shows that a remarkable seasonal variation exists, with a range of 25-33 mg/l seen in both April and May during the two years observation, but only 14-17 mg/l in other months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347866 TI - [Correlating factors to physician utilization among elderly adults]. PMID- 8347867 TI - Quantitative aspects of the matrix-assisted laser desorption mass spectrometry of complex oligosaccharides. AB - Comparative studies of the matrix-assisted laser desorption ionization of complex oligosaccharides were made using a range of mono, di- and tri-substituted benzoic acids, substituted coumarins and cinnamic acids. The best results were obtained with 2,5-dihydroxybenzoic acid (2,5-DHB). Detection limits using this matrix were in the range of 100 fmol for complex and high mannose sugars, some 2-fold better than those obtained with alpha-cyano-4-hydroxycinnamic acid and 10-fold better than with an earlier oligosaccharide matrix, 3-amino-4-hydroxybenzoic acid. The strongest signals were achieved with a matrix-to-sample ratio of about 5000:1. Little correlation was found between the measured peak height and sample loading when 3-amino-4-hydroxybenzoic acid was used as the matrix and the signal appeared to saturate at a sample level of around 30 pmol. However, good correlation was found between the amount of sample loaded onto the target and the response when an analogous compound was used as an internal standard and peak ratios were measured. In contrast to this, the use of 2,5-dihydroxybenzoic acid as the matrix enabled the oligosaccharide to be measured over the range 100 fmol to at least 100 pmol with an excellent linear correlation between sample quantity and response and without the need of a standard. No evidence of saturation was found with this matrix. With 2,5-DHB (other matrices were not tested), the oligosaccharide signal strength was found to fall with increasing molecular weight in a linear manner and similar to that found previously with proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8347868 TI - Ion trap and quadrupole mass spectra of lignin pyrolysates: how well do they compare? AB - Lignin samples from wheat straw, orchard grass, red clover and a synthetic lignin were subjected to pyrolysis gas chromatography/mass spectrometry using both quadrupole (QMS) and ion-trap detector (ITD). ITD mass spectra were comparable with those presented in the National Bureau of Standards (NBS) library and with those obtained by QMS as evaluated by discrepancy factors. Computer-assisted library searches for ITD spectra were successful for 22 of 47 compounds. The other 25 compounds were not present in the library. A typical program and mass spectra are shown. Statistical data are discussed. PMID- 8347869 TI - Mass spectrometric discrimination between per-O-acetylated aldopentoses applied to an oligosaccharide. AB - Unimolecular decomposition spectra of oxonium ions from peracetylated pentoses can be used for identification purposes. The fast-atom bombardment mass spectra of an oligosaccharide with a pentose residue at the non-reducing terminus also contain this oxonium ion, which allows identification of this monosaccharide residue by a tandem mass spectrometry experiment. The applicability of this method is demonstrated using a xylopentaose. PMID- 8347870 TI - Cost effectiveness of laparoscopic surgery: from whose perspective? PMID- 8347871 TI - Complete abdominal exploration is unnecessary during the treatment of cholelithiasis. AB - The development of laparoscopic and non-operative methods for the management of cholelithiasis has been based on the premise that abdominal exploration during cholecystectomy is unnecessary. In the current study, 305 patients undergoing complete abdominal exploration during routine cholecystectomy were evaluated to assess the incidence and significance of intraabdominal pathology found at the time of exploration. While 41 patients (13.4%) were found to have additional diagnosis at the time of exploration, the majority of these were either minor in nature or would easily have been recognized utilizing laparoscopic techniques. Only one patient would have had significant intraabdominal pathology missed by laparoscopic techniques. It can be concluded that abdominal exploration at the time of treatment of cholelithiasis is unnecessary and that laparoscopic cholecystectomy will not compromise patient care in this regard. PMID- 8347872 TI - Comparison of results of KTP/532 laser versus monopolar electrosurgical dissection in laparoscopic cholecystectomy. AB - A total of 641 laparoscopic cholecystectomies performed between January 1, 1991 and December 31, 1991 were reviewed to compare the results of Potassium Titanyl Phosphate (KTP/532) laser versus monopolar electrosurgery in laparoscopic cholecystectomy. KTP laser dissection was used alone in 199 cases (31%), and monopolar cautery was used in 442 (69%). During this same time period, 41 additional procedures were excluded because of conversion to open cholecystectomy. Procedures in which both modalities (N = 24) were used were also excluded from the study. Modality choice was dependent upon operating surgeon's preference. Data were analyzed with student t-test, chi-square with Yates correction, stepwise linear regression analysis, and correlation matrices. Five (2.5%) patients had five major complications when KTP laser dissection was used and 34 (7.7%) patients had 42 major complications when monopolar electrosurgical dissection was used (p < 0.05). Postoperative hospital stay with the KTP/532 laser dissection group was 1.4 +/- 0.06 days and for the monopolar electrosurgical dissection group it was 1.7 +/- 0.08 days (p < 0.05). The duration of the procedures was identical with either modality. The use of the KTP laser for dissection of the gallbladder during laparoscopic cholecystectomy may be a safer procedure with significantly decreased complication rates and savings in length of hospital stay. Although initially a more expensive procedure, the savings in length of hospital stay and treatment of complications may offset the initial expenditure and be worthwhile. PMID- 8347873 TI - Laparoscopic cholecystectomy in patients aged 65 or older. AB - Laparoscopic cholecystectomy is replacing open cholecystectomy in the surgical management of gallstone disease in healthy individuals. However, the role of laparoscopic cholecystectomy in patients thought to be at higher risk for surgical morbidity is still being defined. The course of patients aged 65 or greater who underwent attempted and successful laparoscopic cholecystectomies were reviewed. Eleven patients (12%) were converted from laparoscopic to open cholecystectomy. For the 83 patients completing laparoscopic cholecystectomy, the median time of surgery was 115 min and the median length of postoperative stay was 1 day. Two patients required parenteral analgesia longer than 48 h. Seven patients were admitted and monitored postoperatively, although five of these were preoperatively planned. Five patients were readmitted within 30 days. One patient was admitted with a myocardial infarction, one a subphrenic abscess, one an incarcerated hernia, one with pyrexia and leukocytosis (for which no source was identified), and one for an elective urinary tract procedure. Laparoscopic cholecystectomy provides patients aged 65 or older the same benefits of shorter hospital stay and less pain than it provides younger patients. Age alone should not be a contraindication to attempted laparoscopic cholecystectomy. PMID- 8347874 TI - Stationary and automated laparoscopically assisted technologies. AB - The extent that laparoscopy may impact upon the practice of surgery remains to be clarified. One problem with these techniques is the maintenance of an adequate, stationary visual field in morphometrically different abdomens. This requires the attentive, trained, and skillful utilization of someone or something to operate the camera portal. Herein reported are the theory, advantages, disadvantages, and clinical utilization of mechanical and robotic arm systems to replace this second assistant during laparoscopic surgery. PMID- 8347875 TI - Digital blunt dissection technique to assist laparoscopic gonadectomy in inguinally located/adhered gonads. AB - Laparoscopic gonadal removal in two patients, one with XY gonadal dysgenesis and the other with complete androgen insensitivity is described. In both cases, the gonads were either located deep in the inguinal canal or adherent in that area. Digital blunt dissection using a finger passed through the lateral lower abdominal trocar incision site (12 mm) at the mid-clavicular line of the lower abdomen, combined with external palpation/elevation of the inguinal ring, allowed rapid dissection and isolation of the desired structures and vascular pedicles. PMID- 8347876 TI - Mechanical retraction in laparoscopic surgery: intraoperative cholangiography. AB - The utility of mechanical retraction in laparoscopic surgery is presented. The steps required for its utilization during intraoperative laparoscopic cholangiography are outlined. PMID- 8347877 TI - An overview of laparoscopic surgery. PMID- 8347878 TI - The impact of laparoscopic surgery on health care delivery. The learning curve: skills and privileges. PMID- 8347879 TI - The impact of laparoscopic surgery on health care delivery. Changes in the patterns of patient care. PMID- 8347880 TI - Patients' perspectives of laparoscopic surgery. PMID- 8347881 TI - Laparoscopic surgery: potential for health care cost reductions. PMID- 8347882 TI - The program on outcomes research in technology. PMID- 8347883 TI - Is laparoscopic technology developing too rapidly? Distinguishing experimental technology from state-of-the-art surgery: the industrial perspective. PMID- 8347884 TI - Is laparoscopic technology developing too rapidly? Distinguishing experimental technology from state-of-art surgery: the industrial perspective. PMID- 8347885 TI - Is laparoscopic technology developing too rapidly? Distinguishing experimental technology from state-of-art surgery: the industrial perspective. PMID- 8347886 TI - Is laparoscopic technology developing too rapidly? Distinguishing experimental technology from state-of-art surgery: the industrial perspective. PMID- 8347887 TI - Is laparoscopic technology developing too rapidly? Distinguishing experimental technology from state-of-the-art surgery: the clinician's viewpoint. PMID- 8347888 TI - Laparoscopic cholecystectomy and pregnancy. AB - The risk of operation during pregnancy is a concern to both patients and surgeons. Operative treatment for gallstone disease during pregnancy is therefore performed only when the severity of symptoms exceeds the tolerance of the patient. The insufflation of the abdomen during laparoscopy and the concerns regarding adequate exposure are significant in the performance of such operations. When the indications are appropriate, laparoscopic cholecystectomy can be conducted safely during the course of an intrauterine pregnancy. PMID- 8347889 TI - Laparoscopic excision of a mesenteric cyst. AB - Benign abdominal cystic tumors are rare. They include retroperitoneal, mesenteric, and omental cysts. Most of these lesions present with vague abdominal pain and nausea. Less commonly they will present with bowel obstruction due to external compression. The diagnosis of these tumors is by abdominal ultrasound or computed tomography. Surgical enucleation is the treatment of choice. Laparoscopic surgical techniques are replacing or complimenting open abdominal surgical procedures. As the indications for these techniques increase, newer applications will arise. Presented here is a case of laparoscopic excision of a mesenteric cyst. PMID- 8347890 TI - Laparoscopic treatment of an upper ureteral stone. AB - Extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous lithotripsy have become standard procedures for treatment of ureteral stones. Often, open surgery becomes necessary. A case of bilateral ureteral stones with chronic obstruction is presented in which the successful treatment with laparoscopic ureterolithotomy on one side is described. Laparoscopic ureterolithotomy can be used as an alternative method for stone removal in the upper and middle ureter. PMID- 8347891 TI - Laparoscopic adrenalectomy. AB - Presented is a case of a laparoscopic adrenalectomy and a small series of adrenalectomies performed by more traditional approaches both anterior and posterior. The laparoscopic adrenalectomy compares favorably with operating time and estimated blood loss and resulted in a shorter hospital stay and decreased total disability. PMID- 8347892 TI - Small bowel obstruction following laser laparoscopic cholecystectomy: a case study. PMID- 8347893 TI - The evolution of laparoscopic instruments. PMID- 8347894 TI - Enhancement of antigen-specific humoral and cell-mediated immunity by electric footshock stress in rats. AB - The effect of footshock stress on the induction phase of sensitization to keyhole limpet hemocyanin (KLH) introduced intraperitoneally was studied in adult male Sprague-Dawley rats. Rats were shocked at Days -1, 0, 1, and 3 relative to sensitization with 50 micrograms KLH and 14 days later were intradermally injected with 25 micrograms KLH or were noninjected. Anti-KLH IgG levels were measured in serum by ELISA and were enhanced in stressed versus control rats shocked on Days 0 or 1; splenocyte proliferation to KLH in vitro was also found to be enhanced in shocked rats compared to that in nonshocked rats. Skin at the challenge sites was removed and histologically examined for infiltrate density. There was an increased infiltrate in animals shocked on Days 0 or 1 in comparison to nonshocked controls. The increased humoral and cell-mediated anti-KLH immunity in stressed rats is evidence for enhanced immune function by exposure to footshock proximal to the induction phase of the immune response. The possibility of a generalized increase in immune function in stressed rats is doubtful since splenocyte proliferation to the T-cell mitogens concanavalin A (Con A) and phytohemagglutinin and the B-cell mitogen lipopolysaccharide showed no alteration between control and stressed rats at the time of sacrifice. PMID- 8347895 TI - Splenic norepinephrine is decreased in MRL-lpr/lpr mice. AB - The MRL-lpr/lpr mouse, a genetic model of the human autoimmune disease systemic lupus erythematosus, has been studied extensively to determine the etiology and the pathological course of the disease in lymphoid organs. At approximately 8 weeks of age, splenomegaly develops due to a massive increase in an abnormal population of T cells, resulting in a disruption of the normal splenic architecture. Part of the normal splenic architecture includes postganglionic noradrenergic sympathetic nerve fibers, which can exert influence on a variety of immunological functions. Noradrenergic innervation and norepinephrine content of spleens from both male and female MRL-lpr/lpr mice and MRL(-)+/+ congenic controls were examined at 6, 12, 18, and 24 weeks of age. Norepinephrine content is reduced in MRL-lpr/lpr male and female mice prior to the onset of observed splenomegaly and remains reduced at all ages examined. Remaining noradrenergic fibers are found in their usual compartments, but are greatly diminished compared with controls. PMID- 8347896 TI - Natural killer cell cytotoxicity and T-cell proliferation is enhanced by avoidance behavior. AB - Natural killer (NK) cell activity and mitogen-stimulated spleenocyte proliferation were measured in rats exposed to stress in the form of avoidable and unavoidable shock. Rats that could avoid shock exhibited higher NK activity than either unshocked controls or rats that could not avoid shock. The latter were yoked to the avoidance rats and thus received the same number and frequency of shocks as did the avoidance group. The increased NK activity in the avoidance group appears due to a higher number of NK cells in this group as compared with those in the control or unavoidable shock groups. Additionally, NK activity was found to be proportional to avoidance response rate, with a majority of animals exceeding the minimal temporal avoidance requirement. Mitogen-stimulated proliferation of spleenocytes was also increased several fold in the group that could avoid shock as compared with that which could not and controls. The difference in NK activity and mitogen-stimulated proliferation could not be ascribed to differences in cortisol levels. The results indicate that behavior which results in the avoidance of aversive stimuli can lead to significant enhancement of immune system competence. PMID- 8347897 TI - The inhibitory effect of interferon-alpha on the serotonin-induced impairment of human NK cell activity in whole blood. AB - Serotonin (5-HT) at a concentration of 10(-4) to 10(-10) M impaired the cytotoxicity of human natural killer cells in whole blood. 5-HT added at the onset of the short-term cytotoxic assay had a pronounced inhibitory effect. It is very likely that the 5-HT2 receptor is involved in the inhibition of cytotoxicity because ketanserin, an inhibitor of the 5-HT2 receptor, partially prevented the effect of 5-HT. Treatment with 10(2)-10(4) IU/ml of interferon-alpha before or after the application of 5-HT decreased its inhibitory effect on the cytotoxicity. Radioligand binding studies revealed that the antagonistic effect of interferon was not due to the competition for the 5-HT2 receptors. Cycloheximide, an inhibitor of protein synthesis, did not block the suppression of natural killer activity by 5-HT, but it exerted a blocking effect on the acquisition of resistance to 5-HT induced by interferon. PMID- 8347898 TI - Degradation of enkephalins by rat lymphocyte and purified rat natural killer cell surface aminopeptidases. AB - Enkephalins have been reported to induce an elevation in natural killer (NK) cell cytolytic function. In the central nervous system, the short-lasting biological activity of the enkephalins may be attributable to their rapid hydrolysis at the cell surface. In a similar manner, a potential mechanism for regulating the effects of enkephalins on NK cells is through their degradation at the cell surface. The purpose of this study was to determine if NK cells were capable of enzymatically degrading Met- and Leu-enkephalin and to determine the type(s) of enzymes responsible. We report that rat nylon wool enriched splenocytes, purified NK cells, and interleukin-2 activated NK (A-NK) cells were capable of hydrolyzing the N-terminal Tyr residue from Met- and Leu-enkephalin as determined by high performance liquid chromatography. The rate of Tyr cleavage from Met-enkephalin was approximately twice that of Leu-enkephalin for both splenocytes, NK, and A-NK cells. On a cellular basis, enkephalin degradation was four to five times greater with A-NK cells than with splenocytes. Only a Tyr cleavage product was detected, which suggested the possibility of an aminopeptidase activity. This was confirmed by the ability of bestatin, a specific inhibitor of cell surface aminopeptidases, to almost completely inhibit enkephalin degradation by splenocytes (85%) and A-NK cells (96%). A-NK cells were more sensitive to bestatin inhibition as indicated by their IC50 values (0.01 mM for splenocytes and 0.001 mM for A-NK cells). In addition, the chelator 1,10-phenanthroline was also capable of effectively inhibiting enkephalin degradation, suggesting that the enzyme responsible has the characteristics of a metalloprotease. In contrast to the effects of bestatin or phenanthroline, typical inhibitors of serine and thiol proteases were without effect. PMID- 8347899 TI - Comparative methylprednisolone pharmacokinetics in renal transplant patients receiving double- or triple-drug immunosuppression. AB - OBJECTIVE: To assess the pharmacokinetics of chronic methylprednisolone therapy in renal transplant patients receiving double-drug (methylprednisolone and azathioprine) and triple-drug (methylprednisolone, azathioprine, and cyclosporine) immunosuppression. DESIGN: Parallel, randomized trial. PATIENTS: Fourteen renal transplant recipients (aged 29-65 y) evaluated in a public, university-affiliated hospital clinic. INTERVENTIONS: All patients received their chronic oral dose of methylprednisolone via a 10-20-minute intravenous infusion. MAIN OUTCOME MEASURES: Serum methylprednisolone concentrations were determined by HPLC and were used to generate pharmacokinetic parameters for this drug. RESULTS: The mean daily methylprednisolone dosage was 19 +/- 19 mg in the double-drug group and 9 +/- 2 mg in the triple-drug group. Mean serum creatinine concentrations were 124 +/- 44 and 124 +/- 27 mumol/L, respectively. Mean methylprednisolone clearances were similar in both groups: 405 +/- 205 (double drug) and 373 +/- 365 mL/h/kg (triple-drug) (p > 0.05). Mean steady-state volume of distribution was 1.5 +/- 0.8 L/kg in the double-drug group and 1.3 +/- 0.8 L/kg in the triple-drug group (p > 0.05). Plasma half-life ranged from 1.7 to 4.3 h (mean 2.7) in the double-drug group versus 1.4 to 3.4 h (mean 2.6) in the triple-drug group (p > 0.05). CONCLUSIONS: These data indicate that cyclosporine had no definitive influence on methylprednisolone disposition. The results reveal a wide variation in methylprednisolone metabolism in renal transplant recipients receiving either a double- or triple-drug immunosuppressive regimen. Typically, methylprednisolone is prescribed according to a standardized dosing protocol that assumes minimal interpatient variation. Therefore, the pharmacokinetic variability noted in this study may have important clinical implications regarding the development of chronic toxicity (e.g., osteoporosis, hypothalamic pituitary-adrenal suppression) and the attainment of successful immunosuppression. PMID- 8347900 TI - Loss of efficacy during long-term cifenline therapy: development of antiarrhythmic resistance? AB - OBJECTIVE: To describe the possible development of antiarrhythmic resistance to cifenline, an investigational Class I agent. METHODS: Forty patients with chronic ventricular premature depolarizations (VPDs) underwent dose-ranging studies with cifenline, an investigational Class I antiarrhythmic agent. Patients had a minimum of 30 VPDs/h detected by ambulatory electrocardiographic (ECG) monitoring over a 48-hour baseline placebo lead-in period. Twenty-two patients (55 percent) who initially responded received long-term cifenline therapy. Ambulatory ECG monitoring over 24 hours was repeated during active cifenline therapy at three month intervals and during placebo reintroduction at six-month intervals. RESULTS: After an average follow-up of 28 months, VPD frequency during cifenline therapy was similar to that during initial baseline placebo therapy in 8 of the 22 patients (36 percent) who initially responded. Placebo reintroduction following cifenline failure showed a VPD frequency similar to that with active therapy. All patients had further cifenline dosage increases without success. Plasma cifenline concentrations increased in all patients and were in the high therapeutic range. All 8 patients were switched to other Class I antiarrhythmic agents with successful VPD suppression during treatment with the first alternative drug. CONCLUSIONS: We conclude that antiarrhythmic resistance occurred with cifenline in these patients as (1) initial efficacy was established for a minimum of two years, (2) VPD frequency was similar during cifenline therapy and placebo reintroduction, (3) cifenline therapy failure continued despite further dosage titration, and (4) alternative Class I antiarrhythmic therapy was successful in all patients. Repeat intermittent ambulatory ECG monitoring is necessary not only to assess the continued need for antiarrhythmic drug therapy, but also to establish continued long-term efficacy. PMID- 8347901 TI - Effectiveness of an ambulatory care clinical pharmacist: a controlled trial. AB - OBJECTIVE: To compare two general medicine clinics to determine the effectiveness of an ambulatory care clinical pharmacist in assisting recognition of drug therapy problems for physicians and decreasing drug therapy costs. DESIGN: Controlled trial. SETTING: Two general medicine ambulatory care clinics associated with a large, tertiary-care teaching hospital. PATIENTS: Those with scheduled and completed appointments in the clinics during the two-week study period. METHODS: Medication profiles of patients attending clinic A (pharmacist intervention) and clinic B (no pharmacist intervention) were reviewed by the pharmacist prior to clinic appointments. Potential drug therapy problems were identified at each clinic, but interventions were performed only at clinic A. Postappointment audits determined the number of recommendations implemented at clinic A versus the number of drug therapy problems (potential interventions) recognized and addressed by clinic B physicians independently of pharmacist intervention. Potential and actual savings were extrapolated to one year from the two-week study period. RESULTS: Implementation of interventions at clinic A was greater than at clinic B (p < 0.001). Drug therapy cost savings at clinic A were annualized to yield $185 per intervention. Potential cost savings of $176,724, or four times the pharmacist salary costs, is projected. CONCLUSIONS: An ambulatory care pharmacist is effective in identifying drug therapy problems, resulting in significant cost savings to the institution. PMID- 8347903 TI - Use of ondansetron for control of projectile vomiting in patients with neurosurgical trauma: two case reports. AB - OBJECTIVE: To describe two cases of projectile vomiting that were treated successfully with ondansetron in patients with neurosurgical trauma. Causes and pharmacologic treatments for nausea and emesis are also discussed. DATA SOURCES: Patient data and literature citations from published case reports, review articles, and clinical research reports as identified by MEDLINE. DATA SYNTHESIS: Ondansetron, a potent and highly selective antagonist of serotonin at the 5-HT3 (subtype 3)-receptor, possesses potent antiemetic effects. It has not been associated with the extrapyramidal adverse effects seen with traditional antiemetics. The occurrence of extrapyramidal reactions may limit the usefulness of conventional antiemetics in neurosurgical patients because such agents interfere with serial mental status examinations and lower the seizure threshold. Therefore, ondansetron may be preferable in this patient population. Two patients with head trauma and projectile vomiting were treated successfully with ondansetron following treatment failure with prochlorperazine. These represent the first reported cases of efficacious treatment with ondansetron in neurosurgical trauma patients. CONCLUSIONS: Ondansetron may be the preferred agent for controlling nausea and vomiting in patients with neurosurgical trauma. Controlled clinical trials are needed to evaluate its safety and efficacy in this patient population. PMID- 8347902 TI - Pharmacy practice acts: a five-year follow-up. AB - OBJECTIVE: To rereview the status of state pharmacy practice acts since 1987. Additionally, this report discusses adoption of the 1992 National Association of Boards of Pharmacy Model State Pharmacy Practice Act as the standard state pharmacy practice statute. DATA SOURCES: State codes for 50 states and the District of Columbia, with attention focused on the pharmacy practice acts; Puerto Rico and the Virgin Islands were excluded. CASE LAW SELECTION: Case law utilizing state pharmacy statutes was selected to demonstrate pharmacists' liability. DATA EXTRACTION: The focus on each statute was the statutory definition of the "practice of pharmacy." DATA SYNTHESIS: Twelve pharmacy laws (24 percent) contain no definition of the practice of pharmacy. Compounding (92 percent), dispensing (100 percent), interpretation and evaluation of prescriptions (72 percent), consultation (85 percent), drug utilization review (69 percent), drug product selection (54 percent), drug administration (21 percent), pharmacokinetic consultation and patient assessment (13 percent) were noted in the laws for the remaining 38 states and the District of Columbia. Significant pharmacy activities codified since 1987 include consultation, drug administration, pharmacokinetic consultation, and patient assessment. Statutes defining pharmacy practice impact the profession by affecting liability and by mirroring society's view of the role of the profession. CONCLUSIONS: States have enacted new statutes principally in the areas of progressive pharmacy practice functions since 1987. Enactment of the definition of professional practice contained in the National Association of Boards of Pharmacy Model State Pharmacy Practice Act would serve the pharmacy profession by: (1) creating a uniform professional purpose; (2) creating legal responsibility that reflects contemporary practice; (3) allowing pharmacists to enlarge the scope of their practice as the profession's societal role evolves; and (4) conserving revenues normally consumed by lobbying for constant legislative revisions. PMID- 8347904 TI - Cyclosporine-amiodarone interaction. AB - OBJECTIVE: To report a possible interaction between cyclosporine (CsA) and amiodarone in a kidney transplant recipient. CASE SUMMARY: A 66-year-old kidney transplant recipient with a history significant for hypertension, moderate mitral valve insufficiency, and decreased left ventricular function developed ventricular tachycardia posttransplant and was eventually treated with amiodarone. Maintenance immunosuppression included prednisone, azathioprine, and CsA. CsA concentrations before amiodarone initiation were stable (range 100-150 ng/mL). After amiodarone initiation, the CsA concentration increased more than twofold. Following CsA dosage reduction, concentrations returned to the desired range. The patient did not experience any toxicity with the increased concentration of CsA. DISCUSSION: The possible mechanisms of an interaction between CsA and amiodarone are reviewed. Reports of this interaction in heart transplant recipients are also reviewed. Changes in protein binding, changes in metabolism, or both may explain the interaction. Both CsA and amiodarone are protein bound and metabolized by the cytochrome P-450 enzyme system. CONCLUSIONS: It is likely that there is an interaction between CsA and amiodarone. The exact mechanism of this interaction has not been fully determined. When CsA is administered concurrently with amiodarone, CsA concentrations should be monitored closely and the CsA dosage should be adjusted as necessary. PMID- 8347905 TI - Pulmonary complications following tricyclic antidepressant overdose in an adolescent. AB - OBJECTIVE: To report a case of pulmonary edema following a tricyclic antidepressant (TCA) overdose in an adolescent. CASE SUMMARY: A 14-year-old girl with a history of prior suicide attempts ingested 54 50-mg desipramine hydrochloride tablets (45 mg/kg ingestion). The patient developed a cardiac dysrhythmia and hypotension, which were successfully treated. She subsequently developed pulmonary edema and a clinical picture suggestive of adult respiratory distress syndrome (ARDS). She was successfully managed with fluid restriction, tracheal intubation, application of positive end-expiratory pressure (PEEP), and vasopressors. The patient was discharged without any clinical sequelae. DISCUSSION: Pulmonary complications secondary to TCA overdose have rarely been reported in children. We reviewed literature pertaining to the etiology, epidemiology, pathophysiology, and management of TCA-induced lung injury, as well as other case reports. We discuss the potential relationship between sequelae resulting from TCA ingestion (e.g., cardiac disturbances, hypotension, acidosis, gastric aspiration, pneumonia) and the development of ARDS and pulmonary edema, and relate this association to our patient. CONCLUSIONS: Pulmonary edema and a clinical picture suggestive of ARDS was noted in an adolescent girl who ingested a large quantity of desipramine. Her lung injury may have been the result of a variety of factors including hypotension, metabolic acidosis, possible aspiration, or a direct action on the lung parenchyma by desipramine. We attribute her favorable clinical outcome to early intervention consisting of tracheal intubation, PEEP, fluid restriction, and vasopressor therapy. PMID- 8347906 TI - High transdermal fentanyl requirements in a patient with chronic cancer pain. AB - OBJECTIVE: To report a case of high transdermal fentanyl dosage requirements in a patient with chronic cancer pain. DATA SOURCES: Clinical studies, review articles, and relevant laboratory information. CASE SUMMARY: A 42-year-old woman with cervical cancer was admitted for control of her pain. Her outpatient analgesic regimen was a continuous intravenous infusion of morphine sulfate (MS) via an ambulatory infusion device. Upon admission, supplemental doses of intravenous MS were administered in an effort to eliminate the pain. Transdermal fentanyl therapy was initiated on hospital day 1 at 100 micrograms/h and the MS continuous intravenous infusion dosage was increased. Over the next four days, the patient experienced episodes of inadequate pain control and the transdermal fentanyl dosage was increased in increments of 100 micrograms/h. On hospital day 4 the MS continuous infusion was converted to patient-controlled analgesia (PCA). The patient reported acceptable pain control with a regimen of transdermal fentanyl 500 micrograms/h and MS via PCA and she was discharged home on hospital day 7. CONCLUSIONS: This patient's high transdermal fentanyl dosage requirement was related to disease progression. She experienced an acute pain episode that may have been effectively managed by increasing the dosage of her continuous intravenous MS infusion. PMID- 8347907 TI - Benzodiazepine withdrawal reaction in two children following discontinuation of sedation with midazolam. AB - OBJECTIVE: To report the occurrence of recurrent benzodiazepine withdrawal reactions in two very young children following discontinuation of sedation with midazolam. CASE SUMMARY: A 15-month-old boy with apneic episodes was sedated with midazolam for 12 days with constant infusion. Half a day after discontinuation of the midazolam the boy became restless, tachycardic, and hyperpyrexic. When midazolam was readministered, all symptoms disappeared. Four days later midazolam was again discontinued and within 12 hours the same signs and symptoms reappeared. Midazolam infusion was restarted, and the signs and symptoms disappeared for the second time. After thoracotomy, a 14-day-old boy received intravenous midazolam for sedation for 29 days. Within 12 hours after discontinuation of midazolam he became restless, developed a bulging stomach secondary to aerophagia, and was vomiting. Midazolam therapy was reinstituted and continued for another 2 months by constant infusion. Thereafter, the boy was successfully weaned from artificial ventilation in 5 days under sedation with midazolam. About 12 hours after discontinuation of midazolam the boy became restless, tachycardic, again developed a bulging stomach because of aerophagia, and vomited. When the child was sedated with clorazepate by continuous infusion, the signs and symptoms disappeared. DISCUSSION: Case reports describing benzodiazepine withdrawal reaction upon discontinuation of midazolam were reviewed and compared. The symptoms observed in the children we present resemble those mentioned in the three children and two adults reported previously. Unique in the very young children in this article is the occurrence of gastrointestinal symptoms, which most likely are the result of air being swallowed secondary to severe agitation. CONCLUSIONS: Midazolam withdrawal reactions in adults and children, particularly in an intensive care unit, can be significant. Considerable caution must be taken with relatively long-term administration and abrupt discontinuation of midazolam. PMID- 8347908 TI - Valproate-induced coma: case report and literature review. AB - OBJECTIVE: To report a case of hyperammonemia without hepatic dysfunction as a possible cause of lethargy, stupor, and coma in a woman after valproic acid (VPA) administration, and discuss the possible different mechanisms of ammonia elevation and coma. CASE SUMMARY: A woman diagnosed with complex partial seizures that secondarily generalize was treated with phenytoin (PHT) 250 mg/d for 18 years. Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB) 100 mg/d was added because the seizures were incompletely controlled. The patient developed a progressive inability to walk. She was diagnosed as having PHT intoxication. VPA therapy was begun while PHT was being tapered and progressive impairment of consciousness occurred. This evolved into a coma without focal neurologic signs, and was accompanied by isolated hyperammonemia without hepatic failure. DISCUSSION: Adverse effects attributable to VPA were reviewed in the literature. Occasionally, VPA may lead to severe secondary effects such as hepatic failure and coma. In these cases increased blood concentrations of transaminases, bilirubin, and ammonia have been found. Several reports have stressed the existence of hyperammonemic coma without biochemical evidence of hepatic failure, which is what occurred in our patient. This suggests that isolated hyperammonemia and hepatic failure after VPA treatment may have a different biochemical basis. CONCLUSIONS: VPA-induced coma with hyperammonemia and without evidence of hepatic failure should be considered in patients being treated with PHT or PB when VPA is administered concomitantly. This case report shows the importance of clinical monitoring and immediate drug discontinuation when drowsiness, gastrointestinal symptoms, or lethargy occur. PMID- 8347909 TI - Ondansetron in the treatment of intractable nausea associated with theophylline toxicity. AB - OBJECTIVE: To report the efficacy of ondansetron in the treatment of a patient poisoned with theophylline. PATIENT: A 36-year-old man who ingested 6 g of sustained-release theophylline. INTERVENTION: Ondansetron 8 mg intravenously after clinical failure of other antiemetics. RESULTS: Subjective relief of nausea within minutes, enabling the patient to tolerate multiple doses of activated charcoal and whole bowel irrigation. CONCLUSIONS: Ondansetron may offer an alternative to present antiemetic therapy in the poisoned patient. PMID- 8347910 TI - Effect of seven fluoroquinolones on the determination of serum creatinine by the picric acid and enzymatic methods. AB - OBJECTIVE: To investigate in vitro the interaction of seven fluoroquinolone antibiotics with the determination of serum creatinine by the picric acid and enzymatic methods. DESIGN: This blind, in vitro study assayed duplicate serum samples for creatinine by the picric acid and enzymatic methods with averaged spiked concentrations of 2.71, 13.56, 27.12, and 108.47 mumol/L of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, 1-ofloxacin, sparfloxacin, and temafloxacin. Cefoxitin (in concentrations of 233.9, 1169.6, 1754.4, and 2339.2 mumol/L) was used as a positive control for the picric acid assay. SETTING: University affiliated hospital, Department of Pharmaceutical Services and Clinical Chemistry section of the Department of Pathology. MAIN OUTCOME MEASURE: The serum creatinine samples spiked with the seven substituted fluoroquinolones and cefoxitin were assayed by both the picric acid and enzymatic assays. Statistical analysis compared the spiked samples with blank serum by Student's t-test and concentration ranges were compared by analysis of variance. A statistically significant interference with serum creatinine was p < 0.05. RESULTS: None of the substituted fluoroquinolones interfered significantly with the determination of serum creatinine by either method. Cefoxitin significantly interfered with the determination of serum creatinine by the picric acid method. CONCLUSIONS: Fluoroquinolones do not interfere with the determination of serum creatinine by either the picric acid or enzymatic method. PMID- 8347911 TI - Zinc lozenges for treatment of common colds. PMID- 8347912 TI - Use of hydroquinone as a bleaching cream. PMID- 8347914 TI - Natural products and the athlete: facts and folklore. AB - OBJECTIVE: To contrast scientific facts with suggested manufacturers' claims regarding food supplements (natural products) marketed for enhanced athletic prowess. DATA SOURCES: A MEDLINE search was performed to obtain documentation supporting the claims of natural-product manufacturers. In addition, several references pertaining to pharmacognosy, natural products, herbs, pharmacy practice, and sports medicine were reviewed. Claims were obtained from promotional advertisements in bodybuilding magazines, product labels, and fact sheets for sales representatives in nutrition and health-food stores. DATA EXTRACTION: We reviewed all of the clinical trials, published between 1966 and 1992, relative to the manufacturers' claims regarding these products. DATA SYNTHESIS: Pertinent human and/or animal studies supporting each natural product were compared with the manufacturers' claims. CONCLUSIONS: We found that there was no published scientific evidence to support the promotional claims for a large proportion of the products (8/19, 42 percent). Only 4 of 19 products (21 percent) were associated with any documented human clinical trials supporting their promotional claims. Six of 19 agents (32 percent) had some scientific documentation to support their promotional claims; however, these products were judged to be marketed in a misleading manner. PMID- 8347913 TI - Vancomycin therapeutic drug monitoring: is it necessary? AB - OBJECTIVE: To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients. DATA SOURCES: A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations. DATA SYNTHESIS: The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients. CONCLUSIONS: Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients. PMID- 8347915 TI - Medication compliance in elderly outpatients using twice-daily dosing and unit-of use packaging. AB - OBJECTIVE: To determine the effect of unit-of-use drug packaging of medications on compliance among elderly outpatients treated with complex medication regimens. DESIGN: Nonblind, randomized, clinical trial. SETTING: Geriatric outreach health centers in urban public housing units for independent-living elderly people. PATIENTS: Thirty-one patients (aged > or = 60 y), each taking three or more prescribed medications. Patients were randomly assigned to one of three study groups: group 1 (n = 12), no change in dosing or packaging; group 2 (n = 10), conventional packaging with twice-daily dosing; group 3 (n = 9), unit-of-use packaging with twice-daily dosing. INTERVENTION: A unit-of-use package consisting of a two-ounce plastic cup with a snap-on lid containing all medications to be taken at the time of dosing. MAIN OUTCOME MEASURES: Medication compliance was assessed monthly for six months using tablet counts. RESULTS: Medication compliance was significantly better in group 3 (92.6 percent) using unit-of-use packaging compared with either group 1 (79 percent) or group 2 (82.6 percent) (p = 0.017). Compliance did not differ between groups 1 and 2. CONCLUSIONS: In this small study of elderly outpatients taking three or more medications, unit-of-use packaging and twice-daily dosing improved medication compliance compared with conventional packaging. PMID- 8347916 TI - Drug-induced alterations in serum creatinine concentrations. AB - OBJECTIVE: To provide a comprehensive review of drug-induced alterations in serum creatinine concentrations (SCrs). DATA SOURCES: Information was obtained from a MEDLINE search, reference lists from articles identified in the search, review articles, and abstracts. STUDY SELECTION: Emphasis was placed on clinical studies of direct relevance to clinical practitioners. DATA EXTRACTION: Literature was assessed for its methodology, results, discussion, and conclusion. DATA SYNTHESIS: Two analytical systems to assay SCr are commonly employed in clinical practice--the Jaffe-based and enzymatic methods. Several drugs have been reported to interfere with SCr results obtained with both analytical systems by producing assay interference. In addition, trimethoprim, cimetidine, and salicylates produce elevations in the SCr by altering the normal elimination pathways of creatinine. Phenacemide has been reported to increase creatinine elimination, but the mechanism of this effect is unknown. CONCLUSIONS: Pharmacists should recognize the clinical significance of drug-induced interference with SCr and propose alternative methods of determining concentrations in selected patients. PMID- 8347917 TI - Crossover comparison of drug information online database vendors: Dialog and MEDLARS. AB - OBJECTIVE: To compare Dialog EMBASE with the National Library of Medicine's (NLM's) MEDLARS MEDLINE, TOXLINE, and TOXLIT to evaluate differences among the databases and vendors in a method consistent with routine drug information practice. DESIGN: Crossover comparison. METHODS: NLM MEDLARS databases MEDLINE, TOXLINE, and TOXLIT were searched directly. EMBASE was searched via Dialog Information Services. MEDLINE was searched back to 1980; TOXLINE and TOXLIT were searched back to 1981, reflecting the different database structures. EMBASE was searched back to 1980. To control bias, searches were randomized; identical strategies were used during the same session and were performed by the same trained searcher. RESULTS: Twenty-six drug information requests were compared. The MEDLARS and Dialog databases were generally similar, with no significant differences in the number of potentially relevant references, English references, clinically relevant references, available abstracts, unique citations, time online, and number of questions answered. EMBASE searches were more costly (p = 0.0005). TOXLIT was costlier than TOXLINE and MEDLINE (p = 0.0018). CONCLUSIONS: NLM MEDLARS databases were comparable to Dialog EMBASE. Although MEDLARS provided more total and English-language citations, the differences were small and did not influence the proportion of questions answered. The greatest difference between the vendors was the significantly lower cost of searching on MEDLARS. Although this difference may be partially offset by the significantly shorter search times on EMBASE, the mean 1.9 minutes saved would not recoup the mean $7.89 difference in cost. MEDLARS databases are less expensive for routine drug information requests. PMID- 8347919 TI - Omeprazole administration. PMID- 8347918 TI - Preventing and treating hypertension: can we do better? AB - Although controversy exists, the most recent reports from the NHBPEP provide new and beneficial facts and recommendations relative to hypertension. During the past 20 years, important advances have been made in this field, but there are still opportunities for improvement. PMID- 8347920 TI - Theophylline, ciprofloxacin, erythromycin: a potentially harmful regimen. PMID- 8347921 TI - Polynomial procedure for estimating first-order absorption rate constant. PMID- 8347922 TI - Comment: cefazolin versus ceftriaxone in lower respiratory tract infection. PMID- 8347923 TI - Comment: cefazolin versus ceftriaxone in lower respiratory tract infection. PMID- 8347924 TI - Role of the transcription activator virF and the histone-like protein YmoA in the thermoregulation of virulence functions in yersiniae. AB - The chromosome of Y. enterocolitica encodes a heat-stable enterotoxin, Yst, being related to STI. The capacity to produce Yst generally disappears during storage of the strains. In these strains, the yst gene is intact but remains silent. The pYV plasmid encodes the eleven secreted antihost proteins called Yops as well as the outer membrane protein YadA. The Yops are secreted by a novel, pYV-encoded secretion mechanism. This mechanism which does not involve the removal of an N terminal signal sequence, is encoded by the pYV virA and virC loci. The virC locus contains 13 genes called yscA-M. The virA locus encodes the LcrD membrane protein. The yop, yadA and ysc genes form the yop regulon controlled by transcriptional activator VirF. Transcription of the yop, yadA, ysc and virF genes is controlled by temperature. A chromosome-encoded histone-like protein, called YmoA, is involved in the thermoregulation of the yop regulon, which suggests that this thermoregulation could result from temperature-induced changes in DNA topology. The phenotype of ymoA mutants resembles that of osmZ or drdX mutants of E. coli but YmoA is not the Yersinia homologue of the E. coli histone H1. The YmoA histone is also involved in the silencing of the yst gene. PMID- 8347925 TI - Differential regulation of Bordetella pertussis virulence factors. AB - Bordetella pertussis, the causative agent of whooping cough, regulates its virulence factors coordinately according to environmental parameters such as temperature and certain chemicals. A regulatory locus has been characterized which is essential for this regulation. This bvg locus codes for a two-component regulatory system composed of the sensor protein BvgS and the transcriptional activator protein BvgA. It has been shown that the BvgA and BvgS proteins are sufficient for the transcriptional regulation of some virulence factors such as the filamentous haemagglutinin (FHA) involved in adhesion. The recent identification of new regulatory mutants demonstrates that the regulation of some virulence factors such as the pertussis toxin (PTX) and the adenylate cyclase toxin (CYA) is more complex and involves additional regulatory factor(s). This finding suggests that the regulation of the various virulence factors is coordinated at the highest level of regulation, but there may be differences in the fine regulation of some of the factors such as the adhesins and the toxins. PMID- 8347926 TI - Diffuse adherence of enteropathogenic Escherichia coli strains--processing of AIDA-I. AB - The adherence of pathogenic Escherichia coli to the mucosa of the small intestine is an important step in the development of diarrhoea. To study the molecular basis of the diffuse adherence (DA) pattern of E. coli strains expressing the classical serotypes of enteropathogenic E. coli (EPEC), strain 2787 (O126:H27) was investigated. By expression cloning, a plasmid-derived 6.0 kb DNA fragment was identified which conferred the DA phenotype on recipient K-12 strains. This fragment encoded the 100 kDa adhesin involved in diffuse adherence (AIDA-I) which by mild heat shock treatment was isolated from the surface of the wild-type and recombinant DA-positive strains. Analysis of the entire DNA fragment revealed two open reading frames coding for proteins of 45 kDa and 132 kDa, respectively. The 132 kDa protein has been identified as the AIDA-I precursor protein which after cleavage of the signal sequence undergoes additional C-terminal processing for maturation to AIDA-I. Though the function of the cytoplasmic 45 kDa protein is not known, preliminary evidence indicates that authentic expression of the protein is a prerequisite for the correct processing of the 132 kDa precursor to AIDA-I. The AIDA-I precursor exhibits significant homology to the virG (icsA) protein of Shigella flexneri which apparently plays a major role in the events leading to the intercellular spread of invasive Shigella organisms. PMID- 8347927 TI - The attaching and effacing virulence property of enteropathogenic Escherichia coli. AB - Enteropathogenic Escherichia coli (EPEC) remain an important cause of infant diarrhoea in many parts of the developing world. Essential for virulence is their ability to adhere to the small intestinal mucosa and produce a striking 'attaching and effacing' (AE) lesion characterised by localised destruction of brush border microvilli, intimate attachment of bacteria to the residual apical enterocyte membrane, often in a cuplike pedestal structure, and formation of a dense plaque of actin (and other) cytoskeletal filaments beneath adherent bacteria. Fluorescence actin staining (FAS test) has turned out to be a useful diagnostic test for the AE lesion and also led to the identification of a chromosomal gene, eae, which is necessary but, by itself, not sufficient to produce the AE lesion. The 94 kDa outer membrane protein encoded by eae may be the adhesin which promotes intimate bacterial attachment. The signal transduction pathway which leads to AE lesion formation has yet to be defined although EPEC induced increased levels in intracellular calcium and phosphorylation of specific cell proteins including myosin light chain suggest that EPEC, by binding to a specific host cell receptor, may be promoting a calcium second message which would a) activate the brush border protein villin to cause microvillar breakdown and b) stimulate protein kinase activity to cause the other cytoskeletal rearrangements. PMID- 8347928 TI - Identification of a fibronectin-binding protein as adhesin of Streptococcus pyogenes. AB - The role of streptococcal fibronectin-binding protein (Sfb protein) in the adherence of Streptococcus pyogenes to epithelial cells was analyzed by using a recombinant Sfb fusion protein which was constructed by fusion of the binding domain of Sfb protein to MS2 polymerase. Sfb fusion protein was overexpressed in Escherichia coli, purified from E. coli lysates by FPLC and analysed in binding experiments with 125I-labelled fibronectin and adherence studies with HEp2 epithelial cells. Lysates from E. coli expressing the fusion protein as well as purified Sfb protein competitively inhibited fibronectin binding and epithelial cell adherence of S. pyogenes, whereas streptococcal lipoteichoic acid (LTA), previously suggested to be the adhesin of S. pyogenes, had no effects. Southern blot analysis of chromosomal DNA from various streptococci revealed that the gene coding for the binding domain of Sfb protein was also present in other S. pyogenes strains. These results indicate that fibronectin-binding protein is the major adhesin of S. pyogenes. PMID- 8347929 TI - Polymorphism of the streptokinase gene: implications for the pathogenesis of post streptococcal glomerulonephritis. AB - Recent studies of streptokinase genes from epidemiologically and clinically defined streptococci of groups A, C and G have provided evidence of the polymorphism of the streptokinase locus in the chromosome of pathogenic streptococci. This review considers genetic and pathogenetic data suggesting that there exists a causal relationship between nephritis strain-associated streptokinase production and the initial stages of post-streptococcal glomerulonephritis (PSGN). Currently available sequence information allows to recognize, in the middle of the streptokinase molecule, a major variable region, V1, of about 70 amino acid residues in which sequence identity drops to below 50% when the proteins from nephritogenic and non-nephritogenic strains are compared. The V1 regions, although showing microheterogeneity within either protein category, appear to be more hydrophobic and possess a higher content of ordered secondary structures in the "nephritogenic" molecules. As a working hypothesis, they may be considered the nephrotropic domain(s) with which streptokinases from nephritogenic strains bind to glomerular structures and activate plasminogen in situ, thus triggering the cascade of proteolytic processes leading to PSGN. PMID- 8347930 TI - Identification and characterization of surface proteins from Staphylococcus saprophyticus. AB - Staphylococcus saprophyticus, a well known cause of urinary tract infections, possesses several properties, such as hemagglutination of sheep erythrocytes, adherence to various cell types and production of urease, which may be virulence factors. In this contribution, we summarise the present knowledge about recently discovered surface proteins of Staphylococcus saprophyticus, a 95 kDa surface associated protein (Ssp) and the hemagglutinin, a 160 kDa surface polypeptide. We describe culture conditions conducive to production of these surface proteins and discuss the molecular and clinical implications of our findings. PMID- 8347931 TI - Variation and genetic control of surface antigen expression in mycoplasmas: the Vlp system of Mycoplasma hyorhinis. AB - Surface antigenic diversity in the swine pathogen Mycoplasma hyorhinis is generated by random combinatorial expression and high-frequency phase variation of multiple, size-variant membrane surface lipoproteins (Vlps) which represent the major coat proteins of this wall-less procaryote. The distinctive structural basis for Vlp variation was revealed in a family of several related but divergent vlp genes. These occur in one cluster as single chromosomal copies, each encoding a conserved domain for membrane insertion and lipoprotein processing, and a divergent external domain that changes size by deletion or insertion of repetitive intragenic coding sequences while retaining a distinctive charge motif. Lack of detectable changes in restriction fragment patterns or DNA sequence of vlp structural genes during phase transitions between ON and OFF expression states ruled out long range genomic rearrangements and frameshift mutations as a means of controlling Vlp phase variation. However, highly homologous vlp promoter regions contain a homopolymeric tract of contiguous adenine residues [poly(A)] upstream of the transcriptional start site which is subject to frequent mutations altering its length. These mutations are the only sequence changes detected during phase transitions, and are highly correlated with the expression state of each vlp gene. This suggests a mechanism of transcriptional control regulating Vlp phase variation by critical changes within the poly(A) region affecting the spacing between the -10 and -35 hexamers or a putative regulator binding site. The multiple levels of structural and antigenic diversity embodied in the vlp gene family may provide essential adaptive capabilities for this wall-less microbial pathogen. PMID- 8347932 TI - The ORF6 gene product of the P1 operon of Mycoplasma pneumoniae. AB - The P1 attachment protein gene of Mycoplasma pneumoniae is flanked by two open reading frames with a coding capacity for two proteins of 28 kDa (ORF4) and 130 kDa (ORF6), respectively. An operon-like organization in the order ORF4-P1-ORF6 was proposed by Inamine et al. (11). Instead of an expected 130 kDa protein, two proteins of 40 and 90 kDa were identified as the gene product of ORF6 which might arise from cotranslational cleavage (18). After purification of both proteins, the N-terminal amino acid of the 90 kDa protein was determined. Thus, we identified the putative cotranslational cleavage site before amino acid position 455 (R) (15). Biochemical and immunological studies indicate that both proteins are membrane-associated, exhibiting surface-exposed regions (15). Since a wild type-derived mutant lacking the 40 as well as the 90 kDa protein shows reduced attachment to host cells we suggest that the ORF6 encodes for two proteins which contribute to proper adherence of M. pneumoniae to host cells. PMID- 8347933 TI - Entry of Shiga toxin into cells. AB - The effect of Shiga toxin with mutations in the A fragment has been tested on cells in order to get more information about the processing of the A fragment during entry into the cytosol. A mutant with a deletion between the A1 and A2 domain in the A fragment is resistant to cleavage by trypsin and is less toxic than wild type toxin on both Vero and A431 cells. The results support the view that processing of the A fragment is important for the high toxicity of the wild type toxin. A number of cell lines are resistant to Shiga toxin although they bind the toxin. However, A431 cells can be sensitized by butyric acid treatment, and transport of Shiga toxin to the Golgi apparatus seems to be required for the intoxication in the sensitized cells. The role of retrograde transport through the Golgi apparatus to the endoplasmic reticulum (ER) will be discussed. PMID- 8347934 TI - Activation and secretion of Serratia hemolysin. AB - The hemolysin of Serratia marcescens (ShlA) is secreted into the culture medium and forms small pores of a defined size in erythrocytes and in black lipid membranes. The protein is synthesized as an inactive precursor of 1608 residues which is translocated across the cytoplasmic membrane by the Sec-export system. In the absence of the outer membrane protein ShlB, the ShlA protein (designated ShlA*) stays in the periplasm and displays about 0.1% of the activity of the secreted form. Secretion of ShlA with the help of ShlB is accompanied by its conversion to the hemolytic form. A ShlA derivative consisting of the N-terminal 238 residues of ShlA is secreted by ShlB, showing that the secretion signal resides in the amino terminal part of ShlA. ShlA* can be activated in vitro by a cell lysate containing ShlB, the activated ShlA remains hemolytic upon removal of ShlB. The assumed covalent modification of ShlA* by ShlB occurs in the N-terminus of ShlA since an amino terminal fragment (M(r) 28,000) secreted by ShlB, and a trypsin fragment of ShlA (M(r) 15,000) are both able to convert ShlA* to a hemolytic protein. In contrast to the permanent modification of ShlA* by ShlB, ShlA activity achieved by complementation with the ShlA fragments is abolished upon removal of the fragments. Apparently, the N-terminal portion of ShlA contains the information for secretion through the outer membrane and for insertion into the erythrocyte membrane. This information is lacking in ShlA* formed in the absence of ShlB but contained in the ShlA fragments formed in the presence of ShlB. The latter bind to ShlA* and direct ShlA* into the erythrocyte membrane. The fragments themselves are too short to build pores. The HpmA hemolysin of Proteus mirabilis shows extensive homology to ShlA. In vitro activation of HpmA* by ShlB and complementation by the 28 kDa ShlA fragment indicates a common activation mechanism. PMID- 8347935 TI - The role of hemolysin(s) in the pathogenesis of Serpulina hyodysenteriae. AB - Serpulina (Treponema) hyodysenteriae, an anaerobic beta hemolytic spirochaete, is the etiologic agent of swine dysentery. Not much is known at present about the virulence factors of S. hyodysenteriae. However, the hemolysin production of this bacterium is generally accepted to be a virulence factor. To study the exact role of hemolysin production in the pathogenesis of swine dysentery, the gene encoding a hemolysin, tly, was cloned and its nucleotide sequence determined. After inactivation of this gene, the virulence of a tly-minus mutant in mice was tested. The mutant had reduced hemolysis indicating that the tly-encoded hemolysin was not the only hemolysin produced by S. hyodysenteriae. Mice infected with the tly-minus mutant had fewer cecal lesions than mice infected with the wild-type S. hyodysenteriae. It was concluded that the tly-encoded hemolysin might be an important virulence factor, but not the only one. Since it was demonstrated that spirochaetes can be transformed through electroporation, this has made a genetic approach to elucidate the pathogenesis of spirochaetal infections possible. PMID- 8347936 TI - Bordetella pertussis adenylate cyclase: a toxin with multiple talents. AB - The adenylate cyclase toxin of Bordetella pertussis is a secreted multifunctional protein, endowed with calmodulin-activated catalytic, haemolytic and cytotoxic activities. Residues and domains involved in different functions have been localized and several permissive sites, able to accommodate insertion of peptides without impairing the different functions of the toxin, have been identified. A 400-bp region in the promoter upstream region of the cyaA gene, encoding the toxin, has been defined as the target of transcriptional activation. PMID- 8347937 TI - Listeria monocytogenes--a model system for studying the pathomechanisms of an intracellular microorganism. AB - Virulence of Listeria monocytogenes is determined by a cluster of five genes in the order plcA, hly, mpl, actA and plcB, which are coordinately regulated by a transcriptional activator, termed PrfA. The gene for PrfA is located in front of plcA. Mutations within each of these genes reduce the virulence considerably and render the mutants unable to properly multiply and/or spread within the infected host cells. Under growth-limiting conditions PrfA-dependent proteins are preferentially synthesised. These studies indicate the existence of additional PrfA-regulated proteins in L. monocytogenes. The synthesis of catalase, superoxide dismutase, LmaA and p60 is not under the control of PrfA. These proteins seem to be also associated with virulence of L. monocytogenes. P60 related proteins are found as major extracellular proteins in all Listeria species but only p60 of L. monocytogenes is able to restore the failure of R mutants (exhibiting a drastically reduced synthesis of p60) to adhere to 3T6 mouse fibroblasts. Adherence of L. monocytogenes to the epithelial Caco-2 cells seem to be independent of p60. The p60 protein of L. monocytogenes differs characteristically from the p60-related proteins of the nonvirulent Listeria species. PMID- 8347939 TI - Bacterial adherence and epithelial cell cytokine production. AB - Epithelial cell lines produce the cytokines IL-1 alpha, IL-6 and IL-8 when stimulated with Escherichia coli. The cytokine response is enhanced by P fimbriae. The epithelial cell lines also respond to stimulation with other cytokines. These in vitro findings were confirmed in vivo in patients with E. coli infection who secreted IL-6 and IL-8 into the urine. The observations suggest that epithelial cells play a more active role in the mucosal immune response than previously recognized. PMID- 8347938 TI - Analysis of virulence factors of Legionella pneumophila. AB - Legionella pneumophila, the causative agent of Legionnaires' disease is a facultative intracellular bacterium, which in the course of human infection multiplies in lung macrophages predominantly manifesting as pneumonia. The natural habitat of Legionella is found in sweet water reservoirs and man-made water systems. Virulent L. pneumophila spontaneously convert to an avirulent status at a high frequency. Genetic approaches have led to the identification of various L. pneumophila genes. The mip (macrophage infectivity potentiator) determinant remains at present the sole established virulence factor. The Mip protein exhibits activity of a peptidyl prolyl cis trans isomerase (PPIase), an enzyme which is able to bind the immunosuppressant FK506 and is involved in protein folding. The recently cloned major outer membrane protein (MOMP) could play a role in the uptake of legionellae by macrophages. Cellular models are useful in studying the intracellular replication of legionellae in eukaryotic cells. Human cell lines and protozoan models are appropriate for this purpose. By using U 937 macrophage-like cells and Acanthamoeba castellanii as hosts, we could discriminate virulent and avirulent L. pneumophila variants since only the virulent strain was capable of intracellular growth at 37 degrees C. By using these systems we further demonstrated that a hemolytic factor cloned and characterized in our laboratory, legiolysin (lly), had no influence on the intracellular growth of L. pneumophila. PMID- 8347940 TI - Induction of heat-shock proteins by bacterial toxins, lipid mediators and cytokines in human leukocytes. AB - We studied the influence of a lipid mediator (12-hydroxyeicosatetraenoic acid, 12 HETE), cytokines (IL-6 and TNF-alpha) and different bacterial toxins (alveolysin; exfoliative toxin; toxic shock syndrome toxin 1, TSST-1 and erythrogenic toxin A, ETA) on the expression of heat shock proteins (hsps) in isolated human leucocytes. 12-HETE induces the expression of individual heat shock proteins (65- and 83 kDa) protein in human leukocytes (lymphocytes, monocytes, basophilic granulocytes; LMBs). As was shown by Western blotting (anti-hsp72), IL-6 or TNF alpha induced hsps preferentially in human LMBs and PMNs, respectively. Among the toxins, ETA and TSST-1 were potent inducers of hsps at low toxin concentrations (10 ng/ml). Alveolysin led to the expression of hsps at hemolytic concentrations (1 HU; 700 ng/ml) whereas at subhemolytic concentrations (7 ng/ml), no heat shock response was observed. The induction of heat shock proteins was also accompanied by increased mRNA levels for hsp70 as determined by PCR analysis. In contrast, exfoliative toxin led to a reduction of the hsp signal in PMNs as determined by Western blotting. Finally, it was demonstrated that PMNs which had been pretreated with TNF-alpha and therefore expressed intracellular hsps were more resistant to cytolytic attack by leukocidin than untreated cells. PMID- 8347941 TI - Possible role of bacterial heat-shock proteins in autoimmune diseases. AB - The immune system is continuously exposed to a variety of microbial antigens. It is unavoidable that such antigens may resemble autoantigens, being present in the host. It has appeared now that the immune system is accepting recognition of such "mimicry" antigens and even may have developed a tendency to focus its attention to such antigens. This paper discusses the findings of immune responses to heat shock proteins, as a family of proteins exhibiting extraordinary sequence conservation, creating a high degree of similarity between bacterial antigens and host antigens. On the basis of existing evidence, it is argued that immune responses directed at hsps are part of regulatory mechanisms which enable the immune system to safely contain potentially self-reactive lymphocytes. Furthermore, it is argued that by means of artificial immunization against hsps or selected determinants of hsps, a development of autoimmune diseases may be inhibited. PMID- 8347943 TI - Vaccines in salmonellosis control in animals. AB - 1. It has been demonstrated that it was possible, under the conditions of the former GDR (East Germany), to decisively decrease the occurrence of Salmonella in livestock by means of the consequent combination of a good management including hygienic measures and of immunoprophylactic measures. This is one of the most important conditions for reducing the risk of food poisoning in man. 2. If using Salmonella live vaccines, cross immunity can be put to use. 3. Amount and duration of Salmonella shedding by calves can be decreased using orally administered live vaccines. 4. The immunogenicity of the S. typhimurium mutant serving as vaccine strain for Zoosaloral "Dessau" was retained after its 60-MDa plasmid had been deleted. PMID- 8347942 TI - The cellular immune response against Yersinia enterocolitica in different inbred strains of mice: evidence for an important role of T lymphocytes. AB - Resistance of mice against infection with Yersinia enterocolitica has been shown to be related neither to the Ity locus coding for resistance against infection with Salmonella typhimurium and other pathogens nor to the H-2 locus. From other mouse infection models, e.g., murine leishmaniasis, there is evidence that a different T cell-dependent regulation of the host immune response in various inbred strains of mice determines the susceptibility to the infectious agent. However, until recently, little was known about the cellular immune response against Y. enterocolitica. Thus, in a first approach we used the highly virulent Y. enterocolitica strain WA of serotype O:8 and different inbred strains of mice (C57 BL/6, Balb/c and athymic T cell-deficient C57 BL/6 nude mice) to investigate the cell-mediated immunity against parenteral infection. Comparison of the median lethal dose and of the net-bacterial growth in the spleens of infected mice indicated that Balb/c mice could be considered as Yersinia-susceptible whereas C57 BL/6 mice were relatively resistant. However, in contrast to normal C57 BL/6, athymic T cell-deficient C57 BL/6 nude mice have proved to be highly susceptible to Yersinia infection suggesting that T cells are required for the elimination of the pathogen. This conclusion was supported by histomorphological and immunohistological results indicating that T lymphocytes were present in Yersinia induced tissue lesions. Moreover, the adoptive transfer of Yersinia-specific T cell lines and clones into naive animals mediated significant protection against the pathogen in both Yersinia-resistant C57 BL/6 and in Yersinia-susceptible Balb/c mice. These findings emphasize an important role of T lymphocytes in the host response against Y. enterocolitica infection. PMID- 8347945 TI - Dissection of pathogenetic determinants and their genomic positions for the evaluation of epidemic strains and infection routes. AB - The epidemiology of infectious diseases intends to disclose the infection routes and sources of the respective diseases in order to provide preventive measures. The success of such a task is directly dependent on the knowledge about the special biological quality and the environmental distribution of the causative agents. This will imply extensive laboratory analysis rather than statistical surveys. The laboratory analysis for epidemiological purposes comprises a set of sophisticated methods for the subdifferentiation of the isolates (e.g. serofermentative and electrotyping, genomic fingerprinting). These methods provide circumstantial evidence of genetic and thus, epidemiological relatedness. Also the dissection of the pathogenic personality of the respective infectious agents was shown to have epidemiologic implications. However, the virulence pattern and the pattern of the genomic position of the respective determinants were found to be well conserved. For this reason, the dissection of virulence factors in comparison to other clonal properties must be regarded only as an additional marker for epidemiological discrimination. Moreover, any form of epidemic virulence remains to be detected by future analysis. PMID- 8347944 TI - Survey on newly characterized iron uptake systems of Yersinia enterocolitica. AB - Iron assimilation systems have been shown to be important for virulence in Yersinia enterocolitica. In principle, iron transport in Y. enterocolitica is similarly organized as in Escherichia coli although some differences exist in the siderophores used. A TonB function was identified which in a tonB mutant was complemented by the E. coli tonB gene. Three outer membrane receptors for siderophores were cloned and sequenced: FoxA for ferrioxamine B and E, FcuA for ferrichrome and HemR for heme uptake. In addition, two receptors were identified by mutants: CccA for catechol cephalosporins and FyuA for yersiniabactin, the siderophore produced by virulent yersiniae. In addition, the FyuA protein is assumed to be the pesticin receptor. PMID- 8347946 TI - Properties of Vero cytotoxin-producing Escherichia coli isolated from human and non-human sources. AB - Vero cytotoxin-producing Escherichia coli (VTEC) are an important cause of disease in man and animals. In addition to the production of VT these strains may possess other properties that are required for full virulence. Examples of some recent molecular studies are reviewed. Use of oligonucleotide probes and the polymerase chain reaction provide methods for the identification and typing of different VT genes. Several VTEC have the ability to cause attaching and effacing lesions of the epithelial microvilli. Hybridization experiments with the eae probe (E. coli attaching and effacing) showed homology with VTEC of human origin of eight different O serogroups. Properties of VTEC from human infections have been compared to strains isolated from animals and foods. PMID- 8347948 TI - Variation in MR signal intensity across normal human knee cartilage. AB - Signal intensity (SI) of individual pixels on sagittal magnetic resonance (MR) images of normal human knee cartilage was quantified to investigate whether it was related to cartilage proteoglycan content. In five subjects, images were acquired with spin-echo sequences with a TR msec/TE msec of 1,000 or 700/20 and a three-dimensional gradient-echo (GRE) sequence (60/15). In a sixth subject, the GRE sequence alone was used with 15 degrees, 30 degrees, and 50 degrees flip angles. In all subjects, SI was maximal in pixel layers of the medial zone and minimal at both cartilage edges, resulting in the presence of a bell-shaped curve of interpixel (zonal) SI variation across the cartilage thickness. The magnitude of SI was dependent on the pulse sequence and flip angle, but the bell shape of the SI variation curve was independent of them. For example, in the medial tibial cartilage, the peak SI was highest with the 1,000/20 spin-echo sequence, intermediate with the 700/20 sequence, and lowest with the GRE sequence. The differences were statistically significant. The bell-shaped SI variation curve resembled the curve for zonal variation in cartilage proteoglycan content but not the curves for collagen or free water content. The physiologic basis for this resemblance and the potential usefulness of the findings for early diagnosis of diseases such as osteoarthritis are discussed. PMID- 8347947 TI - Hydrogen-1, sodium-23, and carbon-13 MR spectroscopy of cartilage degradation in vitro. AB - Viable bovine nasal cartilage was examined with magnetic resonance (MR) spectroscopy. Digestion of the proteoglycan matrix by papain or trypsin was accompanied by substantial changes in carbon-13, sodium-23, and hydrogen-1 MR spectra and relaxation parameters, with C-13 MR spectra showing the most pronounced changes. These results indicate the potential of MR spectroscopy (and imaging) for noninvasive evaluation of cartilage disease and monitoring of patients with degenerative joint diseases. PMID- 8347949 TI - Fatty replacement of bone marrow after radiation therapy for Hodgkin disease: quantification with chemical shift imaging. AB - The authors studied the long-term fatty replacement of bone marrow in 23 patients who had received radiation therapy for Hodgkin disease, with T1-weighted magnetic resonance imaging and quantitative chemical shift imaging. T1-weighted images revealed a mostly homogeneous high-signal-intensity pattern, in contrast to the hypointense pattern of nonirradiated marrow. The degree of fatty replacement was objectively assessed with chemical shift imaging, comparing patients to age matched healthy volunteers. The authors found an increase in relative fat signal of 37% in the thoracic spine and 34% in the lumbar spine. The relative fat signal of nonirradiated pelvic and femoral marrow was decreased by 8%, indicating marrow reconversion. No radiation dose dependence was found in the range from 25 to 50 Gy. No signs of marrow regeneration were observed 15-126 months after radiation therapy. With chemical shift imaging, the degree of long-term radiogenic fatty replacement of the bone marrow can be quantified, confirming the lack of regeneration after radiation therapy for Hodgkin disease. PMID- 8347950 TI - Characterization of focal fatty change in the liver with a fat-enhanced inversion recovery sequence. AB - A T1-weighted inversion-recovery (IR) sequence was used to study 15 patients with possible fatty change in the liver. The inversion time (TI) was calculated for optimal suppression of normal liver signal (t-null). Conventional spin-echo (SE) and short TI IR (STIR) sequences were also performed. For seven documented benign focal fatty liver lesions, the T1-weighted IR (fat-enhanced) sequence clearly enabled differentiation of normal from fat-infiltrated liver, whereas three of these lesions were isointense to normal liver with all other sequences. The livers of the other nine patients (two normal, one with diffuse fatty change, two with metastatic disease, one with hemangioma, one with focal nodular hyperplasia, one with simple cyst, and one with micronodular cirrhosis) showed homogeneous reduction of liver signal with the fat-enhanced IR sequence. PMID- 8347951 TI - Noise reduction in three-dimensional phase-contrast MR velocity measurements. AB - The authors have developed a method to reduce noise in three-dimensional (3D) phase-contrast magnetic resonance (MR) velocity measurements by exploiting the property that blood is incompressible and, therefore, the velocity field describing its flow must be divergence-free. The divergence-free condition is incorporated by a projection operation in Hilbert space. The velocity field obtained with 3D phase-contrast MR imaging is projected onto the space of divergence-free velocity fields. The reduction of noise is achieved because the projection operation eliminates the noise component that is not divergence-free. Signal-to-noise ratio (S/N) gains on the order of 15%-25% were observed. The immediate effect of this noise reduction manifests itself in higher-quality phase contrast MR angiograms. Alternatively, the S/N gain can be traded for a reduction in imaging time and/or improved spatial resolution. PMID- 8347952 TI - Renal cancer staging: comparison of contrast-enhanced CT and gadolinium-enhanced fat-suppressed spin-echo and gradient-echo MR imaging. AB - Fifty-three consecutive patients with 61 solid or complex non-fat-containing renal masses compatible with renal cancer were examined with contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging with pre- and postcontrast FLASH (fast low-angle shot) and fat-suppressed spin-echo sequences. CT and MR imaging were performed within a 1-month interval. CT and MR images were prospectively interpreted. Tumor detection and staging were determined in all patients. CT and MR imaging enabled detection of 54 and 58 of 61 renal tumors, respectively. CT and MR imaging showed 34 and 35 of 38 histologically proved renal tumors, respectively, in 31 patients. Tumor size on CT and MR images demonstrated good correlation and correlated well with the size of pathologic specimens of 34 of 38 resected tumors detected with CT and MR imaging (r = .99). Of the 31 tumors in 31 patients who underwent surgical resection, 24 were correctly staged with CT and 29 with MR imaging. CT and MR imaging both enabled correct staging of four of five additional tumors with biopsy proof of tumor stage. A moderate difference in staging was observed between CT and MR imaging (P = .05). CT showed 13 and MR imaging 15 of 15 tumor thrombi. CT and MR imaging both showed 11 of 11 cases of adenopathy. The results suggest that MR imaging is moderately better than CT for the detection and staging of renal cancer. PMID- 8347953 TI - Correlation of cine MR velocity measurements in the internal carotid artery with collateral flow in the circle of Willis: preliminary study. AB - The velocity-phase relationship intrinsic to phase-contrast magnetic resonance (MR) angiography permits the quantitative and qualitative assessment of blood flow. The ability to measure velocity and vessel cross-sectional area allows noninvasive assessment of volume flow rate (VFR) in the internal carotid artery (ICA). Phase-contrast techniques also demonstrate flow direction. Using two dimensional cine phase-contrast angiography, the authors evaluated VFR in the ICA and collateral flow about the circle of Willis in 15 patients with ischemic neurologic symptoms. The VFR in each carotid artery was correlated with the degree of stenosis and presence or absence of abnormal circle of Willis collateral flow. There was a correlation between a decrease in VFR and abnormal circle of Willis collateral flow. In addition, a correlation between severe stenosis and a decrease in VFR was found. In patients with ischemic neurologic symptoms without severe stenosis (< 70% diameter stenosis), no decrease in VFR was seen. It is hoped that flow quantification and directional flow imaging with phase-contrast angiography will help further characterize carotid artery occlusive disease by enabling assessment of VFR changes associated with ischemic neurologic symptoms. This study also supports the hypothesis that two mechanisms- hemodynamic and embolic--play a role in ischemic neurologic symptoms. PMID- 8347954 TI - Single-breath-hold venous or arterial flow-suppressed pulmonary vascular MR imaging with phased-array coils. AB - A method for acquiring pulmonary vascular magnetic resonance (MR) images with either venous or arterial flow suppression is described. The proposed method only marginally increases the overall imaging time compared with conventional flow suppression techniques. This enables an acquisition to be completed within a single breath hold with some selectivity as to flow direction. Instead of applying a spatially selective presaturation pulse before each radio-frequency (RF) excitation pulse, the flow presaturation pulse is applied once every 16-20 RF excitation pulses. To avoid image artifacts and to maintain a steady state, each presaturation pulse interval is followed by a normal imaging segment but with data acquisition turned off. Overall imaging time is increased by two TR intervals for each presaturation segment. For a 256 x 128 matrix acquisition, venous flow presaturation increases overall imaging time by approximately 14 TR intervals, while arterial flow suppression increases imaging time by 10 TR intervals. PMID- 8347956 TI - Pulsatile flow artifacts in two-dimensional time-of-flight MR angiography: initial studies in elastic models of human carotid arteries. AB - Initial experimental and numerical analysis of artifacts due to pulsatile flow in two-dimensional time-of-flight (2D-TOF) magnetic resonance (MR) angiography are presented. The experimental studies used elastic models of the carotid artery bifurcation cast from fresh cadavers and accurately reproducing the twisting and tapering of the human blood vessels, allowing direct comparison of images with and without flow. Prominent image artifacts, including periodic ghosts and signal loss, were produced by pulsatile flow even though flow-compensated gradient waveforms were used. The dependence of artifacts due to partial saturation on pulse sequence parameters (TR and flip angle) was investigated theoretically for a simple pulsatile velocity profile and compared with experimental results from a model of a normal carotid artery. Signal reduction was observed proximal and distal to the stenosis in a model with a 70% internal carotid artery (ICA) stenosis and a model with 90% stenoses in both the ICA and the external carotid artery. Although this study deals exclusively with 2D-TOF imaging, the methods can also be applied to evaluate other MR angiography techniques. PMID- 8347955 TI - Flow pattern analysis in the abdominal aorta with velocity-encoded cine MR imaging. AB - The sites of deposition of atherosclerotic plaque on the aortic wall are considered to be influenced by secondary and retrograde flow patterns that cause regions of altered shear stress. To detect secondary flow patterns and areas of retrograde flow in the abdominal aorta, velocity-encoded cine (VEC) magnetic resonance (MR) imaging was performed at five different levels of the abdominal aorta in nine healthy volunteers. Net retrograde flow (expressed as a percentage of antegrade flow) increased from proximal to distal levels and was maximal (13.8% +/- 11.8) just distal to the origin of the renal arteries. An increase in the duration of retrograde flow over the cardiac cycle was observed from proximal to distal levels. Whereas retrograde flow was present at end systole and early diastole in each volunteer at every level, the duration and amount of retrograde flow during diastole showed high interindividual variation. Such differences suggest the possibility of variable vascular geometric risk factors in the population for the development of atherosclerotic plaque. The location of retrograde flow in the abdominal aorta demonstrated in vivo with VEC MR imaging was close to that obtained with in vitro flow visualization studies in models of the abdominal aorta. PMID- 8347957 TI - Frequency dependence of MR relaxation times. I. Paramagnetic ions. AB - T1 and T2 of paramagnetic ions in free and chelated form were measured over the range of clinical magnetic resonance imaging field strengths (0.02-1.5 T). T1 values agreed with published data; however, to our knowledge, the field dependence of T2 has not been systematically studied before Mn2+, Cr3+, and Fe3+ all showed T2 reduction at high field strengths, although reduction due to Fe3+ was minimal. This is believed to be due to "contact" interactions, which have been previously noted for manganese. No such T2 reduction was seen in the chelates, except that dysprosium chelate (but not free ion) showed an anomalous decrease in T2 at high field strengths, which may possibly be explained by a dephasing effect caused by the large magnetic moment of Dy3+. PMID- 8347958 TI - Frequency dependence of MR relaxation times. II. Iron oxides. AB - The frequency dependence of T1 and T2 was measured for homogeneous suspensions of magnetite and iron oxyhydroxide particles in water with various concentrations of gelatin. The transverse relaxivity showed two types of behavior: (a) For magnetic particles, there was a rapid increase in T2 relaxivity with frequency, followed by a saturation plateau, which accorded with the Langevin magnetization function. From these curves, the magnetic moment of the particle domains was estimated to range from 0.8 to 6.3 x 10(4) Bohr magnetons. (b) For iron oxyhydroxide (ferritin, ferrihydrite, and akaganeite) particles, T2 relaxivity increased linearly with frequency, the slope of the increase characteristic for each particle. T2 relaxivity generally increased with increasing gelatin concentration, corresponding to the measured decrease in the water diffusion coefficient. For iron oxides, homogeneously distributed either as iatrogenic agents or endogenous biominerals, these findings may aid in the interpretation of in vivo relaxivity and the effect on MR imaging. PMID- 8347959 TI - Implementation of wavelet-encoded MR imaging. AB - Reconstructions of images from wavelet-encoded data are shown. The method of MR wavelet encoding in one dimension was proposed previously by Weaver and Healy. The technique relies on selective excitation with wavelet-shaped profiles generated by special radio-frequency waveforms. The result of the imaging sequence is a set of inner products of the image with orthogonal functions of the wavelet basis. Inversion of the wavelet data is accomplished with an efficient algorithm with processing times comparable with those of a fast Fourier transform. The experiments show that wavelet encoding by selective excitation of wavelet-shaped profiles is feasible. Wavelet-encoded images are compared with phase-encoded images that have a similar signal-to-noise ratio, and there is no discernible degradation in image quality due to the wavelet encoding. Potential benefits of wavelet encoding are briefly discussed. PMID- 8347961 TI - MR imaging of knee hyaline cartilage: evaluation of two- and three-dimensional sequences. AB - Magnetic resonance (MR) imaging of cadaveric knees was performed to determine optimal sequences for visualization of hyaline cartilage. Full-thickness cartilage lesions ranging in diameter from 1 to 5 mm and a partial-thickness cartilage lesion 15 mm in diameter were created in the femoral articular surfaces of three cadaveric knees. The knees were then imaged with a 1.5-T imager with various two-dimensional and high-resolution three-dimensional (3D) techniques. After imaging, the knee specimens were sectioned for evaluation. Measurements of cartilage thickness in fast spin-echo images correlated best with those in the gross specimen. Diffuse areas of cartilage thinning were also most accurately identified with fast spin-echo images. Small, focal cartilage defects were best delineated in 3D SPGR (spoiled GRASS [gradient-recalled acquisition in the steady state]) images. PMID- 8347962 TI - MR imaging of muscle and tender points in fibromyalgia. AB - Fibromyalgia is a syndrome manifested by chronic, diffuse musculoskeletal aching and soreness, palpable muscle tender points, and other symptoms. Standardized clinical diagnostic criteria have recently been developed. Skeletal muscle has been postulated as the end organ in this disease. Biochemical, histologic, electromyographic, and conventional radiographic studies have demonstrated no definitive abnormality. This study sought to establish whether magnetic resonance (MR) imaging could demonstrate any abnormality in these patients. Eighteen patients were entered in the study, 14 of whom were able to complete their examinations. T1-weighted, T2-weighted, gradient-echo, and STIR (short-tau inversion-recovery) sequences were performed in all patients, with selected patients examined with T1-weighted, gadopentetate dimeglumine-enhanced sequences. The trapezius and suboccipital regions were imaged in patients who, clinically, had active fibromyalgia. No abnormalities could be detected. The authors conclude that the conventional MR imaging used in this study was unable to depict any primary skeletal muscle abnormality in fibromyalgia. PMID- 8347960 TI - Three-dimensional MR imaging and display of intracranial disease: improvements with the MP-RAGE sequence and gadolinium. AB - Three-dimensional (3D) image rendering was performed in 14 patients who had undergone magnetic resonance (MR) imaging for focal brain lesions. The MR study included the magnetization-prepared rapid gradient-echo (MP-RAGE) sequence with 64 or 128 partitions. Resultant contiguous sections 2.5 or 1.25 mm thick, respectively, were obtained. Images were acquired before and after administration of gadopentetate dimeglumine. Resultant 3D data sets were processed on a commercially available workstation. Correlative surgical observation was performed in four cases. All data sets were successfully processed into 3D images. The precontrast images proved superior to gadolinium-enhanced images for brain surface rendering. Postcontrast images proved superior for reconstruction of tumors and vascular structures. The 64-partition data set proved sufficient for all postprocessing. Coronal orientation was preferred to sagittal orientation for surface rendering because it provided optimal orthogonal orientation of sulcal and gyral brain surface features. Three-dimensional rendition allowed easy superposition of lesion, brain, vessels, and scalp features--all useful for surgical planning. The central sulcus was easily recognized in the midline partitions and traced mediolaterally for projection on the cortical surface. MP RAGE provides a 3D data set that can be obtained in just over 3 minutes, from which clinically useful 3D renderings are possible. The rapidity of acquisition and capability for 3D rendering provides additional clinical utility. PMID- 8347963 TI - "Keyhole" method for accelerating imaging of contrast agent uptake. AB - Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeroes for the missing data is followed, blurring results. Substituting instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be usefully accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradient- and spin echo images are shown. The method is believed to be compatible with other acceleration methods such as half-Fourier reconstruction and reading of more than one line of k space per excitation. PMID- 8347964 TI - Phase-correction method for reduction of B0 instability artifacts. AB - View-to-view phase shifts due to B0 instability are corrected by applying a phase correction to the low-spatial-frequency views. The algorithm described herein assumes that the signal intensity in the space outside of an object represents only noise. A set of phases for the low-spatial-frequency views are calculated by minimizing, in the image, the intensity of the induced artifacts in the space outside of the object. PMID- 8347965 TI - On cerebral lactate production and blood flow in acute stroke. PMID- 8347966 TI - Overexertional lumbar and thoracic back pain among recruits: a prospective study of risk factors and treatment regimens. AB - A total of 395 male infantry recruits were evaluated in a prospective study of possible risk factors for overexertional back pain and the efficacy of drug treatment regimens for this syndrome. Recruits were classified into subgroups of lumbar or thoracic, and paraspinal or spinous process pain. Recruits were divided into three treatment groups: Ibuprofen, Paracetamol, and no drug treatment. Of the recruits, 18% were diagnosed as having overexertional back pain during the course of 14 weeks of training. By multivariate analysis low body mass index was found to be a risk factor for overexertional lumbar pain (p = 0.005) and increased lumbar lordosis a risk factor for overexertional thoracic pain (p = 0.005). Of recruits with overexertional back pain, 65% were asymptomatic by the end of basic training. There was no statistically significant difference between cure rates according to treatment groups. PMID- 8347967 TI - Correlation of motor-evoked potentials, somatosensory-evoked potentials, and the wake-up test in a case of kyphoscoliosis. AB - The ability to monitor the descending motor pathways of the spinal cord during surgery is an important goal in neurophysiologic monitoring of spinal deformities. This report describes a case of a severe spinal deformity for which instrumentation and reduction carried a significant risk of neurologic complications. During the procedure, changes in neurologic status were monitored simultaneously using both SSEPs and tcMMEPs. The reliability of these two complimentary modalities was then verified by concurrent wake-up tests. This case provides documentation of the reliability of tcMMEP responses when an accurate assessment of motor function was necessary. PMID- 8347968 TI - Salvage reconstruction in acute and late sequelae from pyogenic thoracolumbar infection. AB - Nine patients treated surgically for complicated pyogenic osteomyelitis of the thoracolumbar spine are reported. All patients were treated with anterior debridement and stabilization with nonvascularized autogenous fibular strut grafts. In addition, seven underwent a posterior spinal fusion with instrumentation. The average length of follow-up was 25 months. There was no recurrence of infection, no pseudoarthrosis, and the fibular struts appeared incorporated in all patients. Seven patients had postoperative improvement or resolution of their back pain. The use of nonvascularized autogenous fibular strut grafts for reconstruction of the spine following debridement for vertebral osteomyelitis is an effective procedure. The advantages of using the fibula for grafting are its strength and length for spanning several vertebral segments, and it can provide multiple grafts. PMID- 8347969 TI - A prospective study of diagnostic epidural blockade in the assessment of chronic back and leg pain. AB - A consecutive series of 100 patients with back and leg pain were evaluated prospectively. All had a detailed clinical assessment together with radiculography and computed tomography (CT) of the lumbosacral spine. In addition, each patient underwent diagnostic epidural blockade that identified three kinds of response. Injection of local anaesthetic into the epidural space relieved the symptomatic pain--the positive result (51 patients). Local anaesthetic injection had no effect on the symptomatic pain--the negative result (30 patients). In 19 patients, saline injection into the epidural space relieved the symptomatic pain--the placebo result. The results of this investigation were assessed in the light of the number of inappropriate physical signs found on clinical examination, together with the result of the radiculogram and CT scan. No statistical correlation was found with any of these parameters. PMID- 8347970 TI - Magnetic resonance imaging of the postoperative intervertebral disk: the first eight months--clinical and legal implications. AB - Ten patients were followed prospectively after lumbar discectomy, both clinically and with MR imaging, from 2 days to 8 months. The usefulness of MR imaging is limited during the first 2-3 months postsurgery because of severe disruption of the intraspinal anatomic definition. Thus, abnormal MRI findings during this initial period do not correlate with the clinical symptom-free state of patients postsurgery. The use of MR imaging in symptomatic patients is therefore limited. PMID- 8347971 TI - Herniated thoracic disks: treatment and outcome. AB - The optimal surgical approach for thoracic disk herniation is controversial, and long-term follow-up is poorly documented. We retrospectively reviewed the records of 31 patients who underwent surgery for herniated thoracic disks at our institution during a 17-year period (1975-1992). Two patients had multiple disk herniations; 16 of 33 herniated disks occurred at or below the T10-11 level. There were three surgical approaches to diskectomy: laminectomy in four patients, transpedicular surgery in 12, and costotransversectomy in 15. Weakness resolved postsurgery in nine of 18 patients. One patient transiently deteriorated neurologically after a laminectomy, three had wound infections, and two required second operations for their herniated disks. Postsurgery half the patients with symptoms continued to have pain or weakness. PMID- 8347972 TI - CT analysis of pedicles and screw tracts after implant removal in thoracolumbar fractures. AB - Twenty-one burst fractures of the thoracolumbar junction were stabilized with a transpedicular fixator by surgeons experienced in this technique. Screws 5 or 6 mm in diameter were used. After the removal of the device 1 year postsurgery, axial CT scans were obtained of the instrumented vertebrae. Eighty-two pedicles were examined. In 16 pedicles, medial or lateral cortical defects were found. Five screws had intruded into the spinal canal by a maximum of 3.5 mm. In 48 pedicles a correlative comparison with the preoperative examinations was possible. Compared with the dimensions of the pedicles on the preoperative CT scans, 31 had increased in width, and 14 showed deformation indicative of fractures of the lateral pedicle wall. When the screw diameter exceeded 65% of the pedicles' outer diameter, 85% of the pedicles expanded. One of four screws had penetrated the anterior wall of the vertebra. Pedicle screw penetration on the left side above L2 poses potential risk of erosion of the aorta. The use of pedicle screws at the thoracolumbar junction by experienced surgeons carries some risk for malplacement and neurological damage. Mismatch between pedicle dimension and screw size results in pedicle expansion and lateral wall fractures, probably during screw insertion. Preoperative CT examinations should be used to help in choosing appropriate screw diameter presurgery. PMID- 8347973 TI - Trumpet laminectomy for lumbar degenerative spinal stenosis. AB - The clinical and radiologic results of trumpet laminectomy, an improved method of extensive laminectomy preserving the facet joints (n = 35), and extensive laminectomy (n = 15) were compared in patients with degenerative lumbar spinal stenosis. The results were evaluated using a rating system and serial radiographs and a follow-up of 2 to 10 1/2 years (mean, 5.2 years). The overall results corroborate the advantage of the trumpet laminectomy, demonstrating a lower incidence and lower grade of postoperative lumbar scoliosis as well as less symptom recurrence in the trumpet laminectomy group than in the extensive laminectomy group. Risk factors for postoperative spinal instability and scoliosis appear to be facet joint destruction and elderly females with a high level of physical activity. PMID- 8347974 TI - Role of the surgical position in the development of postoperative low back pain. AB - The aetiology of postoperative back pain is contentious. Although the role of the surgical position has not been fully established, the lithotomy position is often implicated. In order to investigate this common surgical complication further, a prospective study has been performed on 101 hysterectomy patients. The supine (52 patients) and the lithotomy (49 patients) positions have been compared and contrasted within this series. Ten patients in the supine group (20%) and seven patients in the lithotomy group (14%) developed postoperative low back pain (p > 0.1). The mean duration of symptoms postoperatively for the whole series was 7 months. We conclude that postoperative backache is an under-estimated complication of surgery and that this problem occurs equally whether the supine or the lithotomy positions are used. PMID- 8347975 TI - Anterior lumbar interbody fusion for discogram concordant pain. AB - Twenty-two patients undergoing anterior lumbar interbody fusion (ALIF) for discogram concordant low-back pain were retrospectively evaluated by objective criteria. Results were poor in all two-level fusions. Among single-level fusions, there were 35% good, 18% fair, and 47% poor results. Patients with previous surgery or workmen's compensation did poorly as a group despite positive discography. Subjective results were difficult to assess. PMID- 8347976 TI - Cervical laminectomy and foraminotomy as surgical treatment of cervical spondylosis: a follow-up study with analysis of failures. AB - Ninety patients were followed after undergoing multilevel cervical laminectomy for cervical myeloradiculopathy secondary to cervical stenosis. Follow-up data was obtained by chart review and phone interview for all patients; 20% were examined at follow-up as well; 77% of patients were improved, 13% without change, and 10% worse at follow-up. No patients deteriorated in the immediate postoperative period. Greater than 50% of severely disabled patients had an excellent result, and 78% improved somewhat. It is concluded that cervical laminectomy is an effective procedure for treating patients with cervical spondylosis causing myeloradiculopathy. Reasons for failure of this procedure, although rarely identified on follow-up examination, are reviewed and briefly discussed. PMID- 8347977 TI - Short segment transpedicular Cotrel-Dubousset instrumentation: a porcine corpectomy model. AB - This study examines changes in stiffness in a three-level spinal construct utilizing transpedicular Cotrel-Dubousset instrumentation. In addition, we evaluated the effect of adding offset laminar hooks at the same level as the superior transpedicular fixation. Porcine lumbar spines (L-1 to L-5) were tested as: (a) intact spine, (b) intact spine with instrumentation, and (c) instrumented spine after L-3 corpectomy. Instrumented constructs were tested with and without laminar hooks placed at the level of superior transpedicular fixation. Constructs were tested in modes of axial compression and torsion in a MTS materials testing machine. The fully instrumented intact spines demonstrated a 28.0% stiffness increase over the intact spines in torsion (p < 0.005) and a 23.1% increase in the mode of axial compression (p < 0.0002). There was no statistically significant difference in axial or torsional stiffness in the instrumented intact spine constructs when hooks were added. In the corpectomy model, addition of the laminar hooks increased stiffness in axial compression an average of 26.9% (p < 0.002) and in torsion an average of 28.1% (p < 0.0005). This increase in stiffness may aid in preventing the postoperative progression of kyphosis noted in studies utilizing similar constructs in clinical application for the treatment of lumbar burst fractures. PMID- 8347978 TI - Late presentation of infection as a complication of Dwyer anterior spinal instrumentation. AB - Delayed presentation of infection is a rare complication of anterior instrumentation and fusion for scoliosis. Three cases that followed the Dwyer procedure are reported. Pain was absent in these patients, but mild constitutional symptoms were present. An elevated erythrocyte sedimentation rate (ESR) is an important indicator of this complication. Two patients developed groin abscesses and sinuses as the hallmark of deep infection. Infection resolved after removal of instrumentation and local debridement. PMID- 8347979 TI - Eosinophilic granuloma of the spine with and without vertebra plana: long-term follow-up of six cases. AB - Vertebral eosinophilic granuloma is a rare condition frequently associated with vertebra plana. In this paper we present six patients with eosinophilic granuloma of the spine; three were without vertebra plana, which represents a diagnostic problem. The mean follow-up was 9 years, (range 2 to 23) and the mean age was 10.8 years at diagnosis. All complained of pain with no neurological deficit. The lesions were located on the vertebral bodies of C4, T9, T10, L1, L2, and L5, respectively. Histologic confirmation of diagnosis was obtained in all patients, two by puncture and four by open biopsy. The patients with vertebra plana (T10, L1, and L5, respectively) were treated conservatively. Long-term follow-up demonstrated total healing of the vertebral body in two and partial rebuilding 8 years after diagnosis in one. Patients without vertebra plana (C4, T9, and L2, respectively) underwent curettage and bone grafting. In the patient with T9 location, a T8-10 anterior arthrodesis with autogenous rib graft was performed. The outcome was satisfactory in all. PMID- 8347980 TI - Lumbar stenosis with osteoporotic compression fracture and neurogenic claudication. PMID- 8347981 TI - Null red blood cell phenotypes: associated biological changes. PMID- 8347982 TI - Monoclonal antibodies against platelet glycoproteins. PMID- 8347983 TI - Fibrin glue in cardiothoracic surgery. PMID- 8347984 TI - Cryoprecipitate: uses and alternatives. PMID- 8347985 TI - Forensic identity testing using highly polymorphic DNA markers: current status and emerging technologies. PMID- 8347986 TI - Interaction of proteins with lipid headgroups: lessons from protein kinase C. PMID- 8347987 TI - Models of lipid-protein interactions in membranes. PMID- 8347989 TI - The effects of phosphorylation on the structure and function of proteins. PMID- 8347988 TI - Functional bases for interpreting amino acid sequences of voltage-dependent K+ channels. PMID- 8347990 TI - What does electron cryomicroscopy provide that X-ray crystallography and NMR spectroscopy cannot? PMID- 8347991 TI - The design of metal-binding sites in proteins. PMID- 8347992 TI - Artificial neural networks for pattern recognition in biochemical sequences. PMID- 8347993 TI - The structure of the four-way junction in DNA. PMID- 8347994 TI - Realistic simulations of native-protein dynamics in solution and beyond. PMID- 8347995 TI - Hydrogen bonding, hydrophobicity, packing, and protein folding. PMID- 8347996 TI - Glycoprotein motility and dynamic domains in fluid plasma membranes. AB - The diffusion measurements of glycoproteins have further supported a fluid mosaic model of membrane structure, but the basis of the lower apparent diffusion coefficients in biological membranes remains incompletely understood. In the specific case of glycoproteins with a single alpha-helix spanning the membrane, studies indicate that the major frictional drag is in the external protein layer and not the bilayer. Only in the erythrocyte membrane does the internal protein layer clearly control the lateral diffusion coefficient of a glycoprotein with a large cytoplasmic domain. In cultured cells, the barriers to lateral displacements over long distances are primarily on the cytoplasmic surface and not in the external matrix. Active movements of individual or small groups of glycoproteins both forward and rearward on cells appear to result from the interactions with moving cytoskeletal structures. Membrane turnover as well as transient attachment to the cytoskeleton can produce dynamic domains in the membrane that would depend on motile activity. Recent technological advances enable simultaneous monitoring of specific cell functions and glycoprotein motility, making it possible to correlate membrane fluidity and active glycoprotein movements with cell function. PMID- 8347997 TI - Mechanisms of membrane fusion. PMID- 8347998 TI - Fast crystallography and time-resolved structures. PMID- 8347999 TI - The control of protein stability and association by weak interactions with water: how do solvents affect these processes? PMID- 8348000 TI - The two-dimensional transferred nuclear Overhauser effect: theory and practice. PMID- 8348001 TI - Should nurses walk away from the scene of an accident? PMID- 8348002 TI - Nurses must improve their knowledge of pharmacology. PMID- 8348003 TI - Prevention of falls among older people at home. AB - The high incidence of falls among older people and the subsequent high rates of potentially preventable morbidity and mortality highlight the need for early identification of risk factors. This article discusses the major contributory factors and the role of community nurses in accident prevention assessment of older people. PMID- 8348004 TI - Smoking control and cessation. AB - Over the last 30 years the prevalence of cigarette smoking in adults in the UK has fallen to around 30%. Smoking will still kill 100,000 people each year well into the next century. Smoking in children is related to whether their parents smoke. Moves to reduce smoking in adults will therefore reduce smoking in children. The Government should be urged to raise taxes on cigarettes and ban advertising. Smoking should be banned from all health care premises. Hospitals should be encouraged to appoint smoking cessation counsellors to work with both staff and patients. PMID- 8348005 TI - Use of thrombolytic therapy in acute myocardial infarction. AB - The use of thrombolytic therapy in the treatment of acute myocardial infarction is now common practice. This article examines the physiological basis of thrombolytic therapy, the contraindications to its use and the nursing care of patients undergoing such therapy. PMID- 8348006 TI - Evaluation in practice. AB - If the benefits of professional nursing are to be effectively articulated, the process of evaluation in practice must be fully exploited. Nurses in the Mid Staffordshire General Hospitals have developed methods to help them evaluate their practice. In this article the principles underpinning these developments are described. PMID- 8348008 TI - Nurses must maintain higher standards in hygiene. PMID- 8348007 TI - Current developments in interprofessional education. AB - The educational services, the health services and the personal social services are complex multiprofessional organizations which depend on both intraprofessional and interprofessional relationships. Such relationships within and between professional groups are being encouraged to enhance teamwork and collaboration between staff in the delivery of services to clients. PMID- 8348009 TI - A moral dilemma: killing and letting die. AB - Most health care professionals believe that there is a clear difference between killing and letting die, i.e. between active and passive euthanasia. Philosophers, however, have repeatedly attacked the moral validity of their argument. This article explores various related issues and theoretical approaches to the distinction between acts and omissions. PMID- 8348010 TI - Legal aspects of first aid and emergency care: 1. AB - The decision whether or not to intervene in a first-aid situation carries certain implications for nurses. This article, the first in a 3-part series, examines nurses's duty to act at the scene of an accident and the legal implications of intervention. PMID- 8348011 TI - Task-oriented hospital workers threaten the role of nurses. PMID- 8348012 TI - Theatre nursing in Uganda. PMID- 8348013 TI - The Ladies' Home Journal Club. PMID- 8348014 TI - Testing for HIV. PMID- 8348015 TI - Can proper condom use be evaluated? PMID- 8348016 TI - Your patient's health and environmental pollution. Great Lakes Health Effects Program. PMID- 8348017 TI - Radiology rounds. Radiography of the right upper abdominal quadrant showing the removal of the common bile duct stone by a wire basket. PMID- 8348018 TI - Dermacase. Atopic dermatitis. PMID- 8348019 TI - Stress and residents' lifestyle. Survey of family medicine residents at McGill University. AB - To study the effects of training on quality of life and work satisfaction, we distributed questionnaires to all McGill family medicine residents. Residents lacked leisure time and were concerned that the heavy workload would affect subsequent quality of care. However, they adapted well to the stress of training. A spouse or partner was an important source of support. PMID- 8348020 TI - Mother, doctor, wife. AB - Women physicians often play a triple role: mother, doctor, and wife. This situation can be extremely stressful. Understanding the stresses of each role and setting priorities to help make each role more fulfilling are important for balancing career and personal life. PMID- 8348021 TI - AIDS, the female patient, and the family physician. AB - Women constitute the most rapidly growing population with human immunodeficiency virus infection in Canada. Problems unique to women and related to HIV include gynecological disorders such as recurrent candidiasis, cervical dysplasia, and neoplasia. Women also face unique psychosocial issues related to their socioeconomic status, pregnancy, and sex. This article addresses these issues. PMID- 8348023 TI - Recurrent urinary tract infections in children. AB - Urinary tract infections are common in children and present in various ways. Diagnosis is based on findings of pyuria and bacteriuria. Management includes adequate and timely investigation, appropriate antibiotics, treatment of underlying contributing factors, and follow-up advice. PMID- 8348022 TI - Anxiety disorders. Focus on obsessive-compulsive disorder. AB - Obsessive-compulsive disorder was once thought to be rare. Recent epidemiologic surveys reveal the lifetime prevalence rate to be as high as 3%. We now have greater understanding of the neurophysiologic and neurochemical basis of this very crippling disorder. Although obsessive-compulsive disorder often starts in adolescence or early adulthood and can last a lifetime, effective treatment enables most patients to lead relatively normal lives. PMID- 8348024 TI - Dyspnea in dying patients. AB - Dyspnea is common in terminally ill patients and is often fairly difficult to control. If specific causes cannot be identified or treated, general measures to relieve symptoms should be used. Nondrug measures (eg, discussion and explanation with the patient) and drug measures (eg, morphine) can be used to control the dyspnea, although side effects, such as sedation, can be problematic. PMID- 8348025 TI - Familial testicular cancer. What role does heredity play? PMID- 8348026 TI - [The effect of bromocryptin on rotational activity in rats]. AB - The experiments were made in rats with unilateral lesion to the nigrostriatal tract, which was induced by the highly active dopaminergic neurotoxin 1-methyl-4 phenyl-pyridinium. The rotational activity of rats was evaluated after intragastric and subcutaneous bromocryptine given in a single dose of 10 mg/kg and 25 mg/kg one, two, three and four times. The highest effect of the drug was seen when it was used in the maximum dose of 25 mg/kg, but when the agent is repeatedly given in the above dose, it failed to enhance the rotational activity of rats. The findings may provide evidence for possibilities of increasing the doses of bromocryptine in practical medicine, and for designing the injectable dosage form of the drug. PMID- 8348027 TI - [The effect of the calcium channel blockers cinnarizine and flunarizine on the duration of hexobarbital-induced sleep i rats]. AB - The effect of the calcium channel blockers cinnarizine (20 mg/kg) and flunarizine (10 mg/kg) on hexobarbital sleeping time in rats has been studied. We have found that cinnarizine when applied intraperitoneally once 1 h or 4 h before hexobarbital and repeatedly for 5 days once daily prolongs sleeping time significantly. When cinnarizine has been introduced simultaneously with phenobarbital (60 mg/kg) for 5 days once daily the sleeping time that was expected to be shortened by phenobarbital only has been obtained to return to control values. Flunarizine has not been found to affect sleeping time significantly either alone or in the presence of phenobarbital. Latencies have not been altered by any of both agents. PMID- 8348028 TI - [The effect of cerebrocrast and nicardipine on the blood supply and metabolism of the brain in cats with intracranial hemorrhage]. AB - Intravenous cerebrocrast, 1 g/kg/min, and nicardipine, 0.5 g/kg/min, given to cats during 60 min one day after cerebral hemorrhage were found to produce an improvement of cerebral blood supply and oxygen consumption along with a moderate fall of blood pressure. The favourable effect of cerebrocrast on brain oxygen and carbohydrate metabolism was mediated by increased brain blood supply. As compared to cerebrocrast, nicardipine induced a more prolonged antihypertensive response and more pronounced effects on cerebral tissue metabolism, by substantially decreasing brain lactate production. PMID- 8348030 TI - [The anti-arrhythmia action of low-molecular polyvinylpyrrolidone in experimental arrhythmias]. AB - The experiments on 258 albino rats and on 74 albino mice have established that low molecular polyvinylpyrrolidone (PVP) has antiarrhythmic effects. When administered intravenously on a adrenaline model of arrhythmia, PVP and ethmozine showed a very close activity, but PVP resulted in a lower incidence of mortality and proarrhythmia. The action of PVP was weaker than that of ethmozine when they were used in an aconitine model. Oral PVP acted on aconitine-induced arrhythmia stronger and longer than did ethmozine. It is advisable to study the mechanisms of antiarrhythmic activity of PVP. PMID- 8348029 TI - [Propofol suppresses sympathetic activity and inhibits the baroreceptor reflex in waking rats]. AB - The effects of propofol on sympathetic nerve activity and on the baroreceptor reflexes were examined in male Wistar rats. Sympathetic nerve activity was recorded directly from a renal nerve electrode placed earlier; baroreceptor reflex activity was estimated by changes in blood pressure (BP) and heart rate (HR) induced by the vasopressor phenylephrine, or the vasodilator, nitroprusside. Awake animals were anesthetized with propofol (10 mg/kg iv bolus, followed by approximately 35 mg/kg/hr by infusion) for 30 min. During the first 3 minutes, propofol increased sympathetic nerve activity by 113%, while mean arterial pressure was lowered to 85% of control. After 20 minutes, both sympathetic nerve activity and blood pressure had declined by 14% below baseline. Heart rate was stable at the level of approximately 110% throughout. Propofol also attenuated the sensitivity of chronotropic and sympathetic components of the baroreceptor reflex (i.e., to 23-43% and 25-34%, respectively). Thus, propofol lowers blood pressure by a central mechanism attenuating sympathetic nerve activity and sensitivity of baroreceptor reflex. PMID- 8348031 TI - [The anti-arrhythmic action of exogenous creatine phosphate and its effect on myocardial electrophysiological parameters in acute heart failure]. AB - The experiments on rats with overload heart failure have shown that creatine phosphate (CP) used in a single dose at the peak of severe signs of cardiac decompensation was found to produce a short-term normalization of rhythm and an increase in heart rate. With multiple doses, the agent slowed down the development of bradycardia, prevented arrhythmias and promoted the rise of longevity in the experimental animals. At the same time, exogenous CP failed to affect energy-dependent processes of re- and depolarization which were impaired in the myocardium in acute heart failure. PMID- 8348032 TI - [The use of L-DOPA for treating myocardial infarct patients]. AB - Clinical and experimental studies showed a high therapeutic activity of L-DOPA in combination with traditional methods of infarction treatment. L-DOPA promoted a rapid disappearance of heart failure symptoms and accelerated reparative processes by restoring the activity of the sympathetic nervous system. Correctness of the experimentally developed basically new scheme for administration of neurotropic drugs to patients with infarction depending on the disease stage has been validated. PMID- 8348033 TI - [The new antidepressant tetrindole]. AB - The antidepressive effects of tetrindole versus pyrazidole (pirlindole) and imipramine were studied in animal experiments. Tetrindole was found to be more active than pyrazidole and imipramine in a behavioral model of Porsolt, in antagonism with reserpine, in potentiation with 5-hydroxytryptophan, L-dopa and clonidine. The action of terindole is related to its ability to exert reversible inhibitory effects on MAO A activity. Tetrindole is less toxic than pyrazidole and imipramine. PMID- 8348034 TI - [Changes in left ventricular diastolic function and in tolerance to physical loading under the influence of finoptin in stenocardia patients]. AB - A total of 45 patients aged 53.6 +/- 6.1 years who had Functional Class II-IV angina pectoris were examined. In patients with stable angina and normal left ventricular diastolic pressure, a moderate antianginal effect of finoptin was shown to be associated with decreased myocardial afterload. The normalizing effects of finoptin on baseline left ventricular diastolic dysfunction along with lower myocardial afterload resulted in an increase in coronary reserve and a more pronounced antianginal effect. PMID- 8348035 TI - [The effect of the experimental androgenization of the male on the physical and sexual development of his progeny]. AB - The author estimated the impact of exogenous testosterone administration (1 mg/kg) to the male rats on the postnatal development of their offspring. The males were copulated with intact females 48 and 2 days after injection. The treatment of the male rats with testosterone 2 days before mating caused disorders in the sexual development and behavior formation of offspring of both sexes. The exogenous testosterone effects on spermatoblasts of the father promoted to the development of disorders in the formation of behavioral and emotional activities only in the female offspring. PMID- 8348036 TI - [The antiaggregant activity of the synthetic antioxidant emoxipin]. AB - The action of the synthetic antioxidant aemoxipin, 3-oxypyridime derivative on platelet aggregation was studied in 8 patients with ischemic heart disease and cardialgias. An hour later after an intravenous injection in a dose of 5-10 mg/kg, aemoxipin reduced platelet aggregation by 25% (p < 0.05), inhibited the reaction of "release" and spontaneous platelet aggregation. The same effect of the drug was demonstrated in the aggregation caused by ADP action on platelets preliminarily activated by minimum adrenaline concentrations in a tube. Our results are in agreement with the data of other investigators concerning a direct, non-specific nature of aemoxipin action on cellular membranes. PMID- 8348038 TI - [A combination of immunostimulants as a method for correcting secondary immunodeficiencies]. AB - The specific features of the action of combinations of immunostimulants (levamisole, prodigiozan, methyluracil) on a primary immune response to EB, GST and resistance to experimental infection have been studied. It has been shown that levamisole eliminates stimulation by methyluracil and prodigiozan of a primary immune response, lithium carbonate is also an antagonist of prodigiozan. Vitamin E increases the stimulating effect of prodigiozan rather than oxymethacil. The effect of vitamin A depends on the dose. Levamisole does not change the influence of prodigiozan and methyluracil on GST and, like prodigiozan, suppresses GST stimulated by lithium carbonate. The combination of prodigiozan and methyluracil to a large extent than the agent given alone increases resistance to an infection and efficiency of antibiotic therapy. The combination of methyluracil and levamisole increases only the effect of the antibiotic. PMID- 8348037 TI - [The effect of calcium antagonists on carbohydrate and lipid metabolism in diabetes mellitus]. AB - The effect of calcium antagonists: nifedipine (corinfar, cordapheg), sensit, finoptin, foridon on carbohydrate and lipid metabolism was studied in intact and "alloxaned" rats as well as in non-insulin-dependent diabetes patients. It was found that the calcium channel blockers did not change glucose tolerance, normalized carbohydrate metabolism in some patients and decreased the level of triglycerides, B and pro-B lipoproteins. In some cases in intact and alloxane rats treated with finophin (isoptin), lactate decrease in blood and a tendency to insulin increase were often observed. The lipid metabolism was unchanged. PMID- 8348039 TI - [The enhancement of immune suppression by local laser irradiation in rats exposed to cyclophosphane]. AB - The authors experimentally studied where low-energy laser radiation (LELR) can be used to enhance cyclophosphanum-induced immunodepression. Preliminary LELR of the adrenal region and cyclophosphanum, 4 mg/kg, resulted in a more profound decrease in the intensity of a primary immune response as compared to the controls received a pseudoradiation and the cytostatic in the same dosage. The findings suggest that laser radiation can be applied to the adrenal region in the clinical setting to reduce a dose of the cytostatic administered and hence adverse effects, by preserving the therapeutical level of immunodepression. PMID- 8348041 TI - [The pharmacokinetics and pharmacodynamics of trental in pregnant women with chronic placental insufficiency]. AB - Examining the relationship between the pharmacokinetic characteristics of trental, its effect on platelet aggregation and adverse effects in pregnant females with chronic placental failure has allowed the optimal dosage regimen to be recommended in the third trimester in this abnormality. Its daily dose was found to be 400 mg (100 mg x 4). PMID- 8348040 TI - [The effect of new biologically active substances on effector T-lymphocytes in vitro]. AB - Levamisole has been demonstrated to stimulate the activity of T effectors in patients with rheumatic arthritis directly and indirectly via production of the factors influencing effector functions. The organosilicon compound minval was beneficial both in patients and donors. Its activity was mediated by the production of factors in donors, whereas in patients it showed direct and indirect actions, being higher than that of levamisole. The bioflavonoid derived from the Rosa L. root was shown to exert no action on T-effector function. PMID- 8348042 TI - [The efficacy of hydroxycinnamic acids in toxic lesions of the liver]. AB - The albino rat experiments studied the pharmacological action of oxycinnamic acid derivatives in acute tetrachloromethane-induced hepatic dystrophy and combined CCl4-ethanol-induced hepatic lesion. The tested agents were found to produce cholagogic, membrane-protective, and antioxidative effects in these hepatic abnormalities, thus improving the functional (cholate- and glycogen-synthetic) parameters of the liver. PMID- 8348043 TI - [The effect of nooglutil and piracetam on different forms of operant learning]. AB - We studied effects of a new drug with nootropic action nooglutil (N-(5 hydroxynicotinoil)-L-glutaminic acid, OHK-10) on initial stages of different forms of operant behaviour in rats, namely avoidance learning in Shuttle box, in Skinner box and on T-maze reflex with water reward. Comparing dates resulted from these three methods permitted evaluation of effects of the drugs on learning. Both drugs had no effects on avoidance response in shuttle box and T-maze reflex with water reward. Nooglutil enhanced escape and avoidance responses meanwhile piracetam improved only escape response. PMID- 8348044 TI - [The effect of dimephosphon on the barrier protective function of the skin during long-term local use]. PMID- 8348045 TI - [The effect of nitroglycerin on the Ca2+ ion level in the cytoplasm of human lymphocytes]. AB - Fluorescence was used to examine the effects of nitroglycerin (60 microM) on basal and mitogen-induced (ConA, 25 micrograms/ml) Ca2+ levels in the human lymphocytic cytoplasm. Calcium-blocking effect of nitroglycerin was markedly shown in the medium containing 1 mM CaCl2 and virtually absent in calcium-free buffer. It is concluded that nitroglycerin affects cellular Ca2+ entry. A 120 minute preincubation led to a complete loss of the inhibitory effects of the drug on mitogen-induced Ca2+ responses of lymphocytes. Human lymphocytes are proposed as an experimental model for investigating the effects of nitrates and the mechanisms of their tolerance development. PMID- 8348046 TI - [The effect of antiparkinson preparations on the self-stimulation reaction of rabbits in a helium-oxygen environment under increased pressure]. AB - The authors studied hypothalamic self-stimulation of 30 rabbits in hyperbaric heliox after intraperitoneal injections of L-DOPA, melanostatin, and cyclodol. The frequency of self-stimulation was decreased with 40 atm of heliox. After L DOPA administration, a reduction of self-stimulation was twice less than that in heliox without pharmaceuticals. PMID- 8348047 TI - [Bradycardia preparations--a new class of antianginal agents]. PMID- 8348048 TI - [Aldehydes and brain functions]. PMID- 8348049 TI - [The spatial memory of animals studied by using the radial maze in psychopharmacology and neurotoxicology]. PMID- 8348050 TI - [The pharmacokinetic interaction of theophylline with preparations from other pharmacological groups]. PMID- 8348051 TI - [Lithium ion modulation of the neuronal responses evoked by monoaminergic receptor agonists]. AB - The authors studied the action of lithium ions on the responses of rat dorsal root ganglion neurons and frog spinal motoneurons evoked by monoamine agonists using the microelectrode technique. Lithium ions reversibly inhibit the depolarizing responses of spinal sensory neurons and motoneurons evoked by activation of muscarinic choline-, alpha 1-adreno-, and 5-hydroxytryptamine2 receptors, but enhance the hyperpolarizing neuronal responses evoked by activation of 5-hidroxytryptamine1A receptors. PMID- 8348052 TI - Misclassification of genetic susceptibility biomarkers: implications for case control studies and cross-population comparisons. AB - Phenotype and genotype markers of genetic susceptibility are of increasing interest in case-control studies of cancer. It is well established that bias to the odds ratio is caused by less-than-perfect assay sensitivity and specificity and varies with risk factor prevalence. As such, the observed variation in odds ratio between studies of genetic markers and cancer risk may be real, or may be attributed, in part, to variation in assay accuracy or in risk factor prevalence (e.g., prevalence differences between racial groups). The latter can be a particular concern when the prevalence of the "at risk" polymorphism in one or more populations is either very high (e.g., > 85%) or very low (e.g., < 15%). For example, even very high sensitivity (e.g., 98%) can produce substantial bias to the odds ratio when the risk factor prevalence is high. Under some prevalence conditions, however, assays with only moderate accuracy are sufficient and result in minimal bias to the odds ratio. Understanding misclassification in the context of marker prevalence may help to explain disparate findings in the literature and should assist investigators in selecting markers that are appropriate for future studies. PMID- 8348054 TI - Diversity in the association between occupation and lung cancer among black and white men. AB - A population-based case comparison study of incident lung cancer and occupational risk factors was conducted in the tricounty Detroit metropolitan area. Nearly 6000 lung cancer cases and a comparison group of 3600 colon cancer cases were interviewed. This report includes 3792 white and black male lung cancer cases and 1966 black and white colon cancer referents. Cigarette smoking, age at diagnosis, and lifetime work history were assessed to determine the relationship between length of employment in specific occupations and industries and lung cancer. Diverse patterns of association between work history and lung cancer were observed for black and white men. Significant associations were seen between lung cancer and increasing length of employment in the following occupations: for white men, concrete and terrazzo finishers, grinding machine operators, heat treating machine operators, miscellaneous machine operators, truck drivers, driver sales, and laborers; for black men, farm workers, automobile mechanics, painting machine operators, furnace operators, and garbage collectors; for both black and white men, farmers, slicing and cutting machine operators, and garbage collectors. Distinct patterns for black and white men also were observed for length of employment by industry. This study clearly demonstrates the need to include black men in studies of occupational cancer etiology and to evaluate black and white men separately. It also indicates the necessity for cigarette smoking history to accurately assess workplace cancer risks. We propose guidelines for incorporating the use of biomarkers into further studies of occupational cancer epidemiology. PMID- 8348053 TI - A case-control study of element levels and cancer of the upper aerodigestive tract. AB - A population-based case-control study was conducted in western Washington state to investigate possible dietary risk factors for laryngeal, esophageal, and oral cancers. Using results from a food frequency questionnaire, past dietary intakes of iron, zinc, and calcium were estimated for 661 cases and 466 controls. Clippings were also taken from the nails of both halluces to determine concentrations of iron, zinc, calcium, chromium, and cobalt in 507 of the cases and 434 of the controls. After adjustment for smoking, alcohol, and dietary beta carotene and vitamin C intake, individuals who reported dietary intakes of iron and zinc in the upper quartile were less likely to develop cancers of the larynx and esophagus than were individuals with intakes in the lowest quartile [odds ratios (OR), 0.5 for iron and 0.1 for zinc]. However, there were no significant differences in zinc concentrations in nail tissue between subjects with these types of cancer and controls. Esophageal cancer cases had higher nail concentrations of iron and calcium than did controls (OR, 2.9 for high versus low quartiles of iron; OR, 2.6 for high versus low quartiles of calcium). Individuals who developed esophageal or oral cancer were more likely to have elevated cobalt concentrations in their nail tissue than were individuals without cancer (OR, 9.0 and 1.9 respectively, for high versus low quartiles). The results of this study suggest that there may be differences in mineral intake or metabolism between individuals who develop some carcinomas of the upper aerodigestive tract and those who do not. PMID- 8348055 TI - Relation of endometrial cancer risk to past and contemporary body size and body fat distribution. AB - In a multicenter case-control study that included 403 cases and 297 controls, we examined the relation of past and contemporary body size, including body fat distribution, to the risk of endometrial cancer. The relative contributions of past and contemporary body size were assessed by examining weight and height histories provided by the subjects. Anthropometric indicators thought to reflect early environmental influences (e.g., height and sitting height), current weight, and fat distribution patterns were measured directly. Height was not a risk factor for endometrial cancer, but inexplicably, sitting height was inversely associated with risk. Weight during early adulthood appeared to be directly related to disease risk, but the association was explained by contemporary weight and thus weight gain during adulthood. While contemporary weight was associated with risk of endometrial cancer, the effect was restricted to those in the top quartile. Women whose measured weight at interview exceeded 78 kg had 2.3 times the risk of those weighing less than 58 kg (95% confidence interval, 1.4 to 3.7). Upper-body obesity (waist-to-thigh circumference ratio) was a risk factor independent of body weight. After adjustment for weight, the relative risks of endometrial cancer across increasing quartiles of upper-body obesity were 1.0, 1.5, 1.8, and 2.6 (P for trend < 0.001). These data indicate that both obesity and the distribution of adipose tissue accumulated during adult life increase endometrial cancer risk substantially. PMID- 8348057 TI - Contribution of occupation and diet to white blood cell polycyclic aromatic hydrocarbon-DNA adducts in wildland firefighters. AB - Wildland (forest) firefighters are exposed to a wide range of carcinogenic polycyclic aromatic hydrocarbons (PAH) in forest fire smoke. PAH undergo metabolic activation and can subsequently bind to DNA. In this study, we investigated the association between occupational and dietary PAH exposures and the formation of WBC PAH-DNA adducts in a population of wildland firefighters. An enzyme-linked immunosorbent assay using an antiserum elicited against benzo(a)pyrene-modified DNA was used to measure PAH-DNA adducts in WBC obtained from 47 California firefighters at two time points, early and late in the 1988 forest fire season. PAH-DNA adduct levels were not associated with cumulative hours of recent firefighting activity. However, firefighters who consumed charbroiled food within the previous week had elevated PAH-DNA adduct levels, which were related to frequency of charbroiled food intake. These findings suggest that dietary sources of PAH contribute to PAH-DNA adduct levels in peripheral WBC and should be evaluated when using this assay to assess occupational and environmental PAH exposure. PMID- 8348056 TI - Serum micronutrients and the subsequent risk of cervical cancer in a population based nested case-control study. AB - A nested case-control study was conducted in Washington County, MD, to determine whether low serum micronutrients are related to the subsequent risk of cervical cancer. Among the 15,161 women who donated blood for future cancer research during a serum collection campaign in 1974, 18 developed invasive cervical cancer and 32 developed carcinoma in situ during the period January 1975 through May 1990. For each of these 50 cases, two matched controls were selected from the same cohort. The frozen sera of the cases and their matched controls were analyzed for a number of nutrients. The mean serum levels of total carotenoids, alpha-carotene, beta-carotene, cryptoxanthin, and lycopene were lower among cases than they were among controls. When examined by tertiles, the risk of cervical cancer was significantly higher among women in the lower tertiles of total carotenoids (odds ratio 2.7; 95% confidence limit, 1.1-6.4), alpha-carotene (odds ratio, 3.1; 95% confidence limit, 1.3-7.6), and beta-carotene (odds ratio, 3.1; 95% confidence limit, 1.2-8.1) as compared to women in the upper tertiles and the trends were statistically significant. Cryptoxanthin was significantly associated with a lower risk of cervical cancer when examined as a continuous variable. Retinol, lutein, alpha- and gamma-tocopherol, and selenium were not related to cervical cancer risk. Smoking was also strongly associated with cervical cancer. These findings are suggestive of a protective role for total carotenoids, alpha carotene and beta-carotene in cervical carcinogenesis and possibly for cryptoxanthin and lycopene as well. PMID- 8348058 TI - Increased sensitivity for determination of polycyclic aromatic hydrocarbon-DNA adducts in human DNA samples by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). AB - A competitive enzyme-linked immunosorbent assay (ELISA), the most frequently used immunoassay for the determination of polycyclic aromatic hydrocarbon-DNA adducts in human tissues, has been modified to achieve approximately a 6-fold increase in sensitivity. The new assay, a competitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) has utilized the same rabbit antiserum as the ELISA, antiserum elicited against DNA modified with benzo[a]pyrene. However, the alkaline phosphatase conjugate has been replaced with a biotin-europium-labeled streptavidin signal amplification system, and the release of europium into the solution forms a highly fluorescent chelate complex that is measured by time resolved fluorometry. The DELFIA has achieved a 5- to 6-fold increase in sensitivity for measurement of DNA samples modified in vitro with benzo[a]pyrene, for cultured cells exposed to radiolabeled benzo[a]pyrene, and for human samples from occupationally exposed workers. The assay has been validated by comparison of adduct levels determined by DELFIA, ELISA, and radioactivity in DNA from mouse keratinocytes exposed to radiolabeled benzo[a]pyrene. Human lymphocyte DNA samples from 104 Hungarian aluminum plant workers were assayed by ELISA and compared to blood cell DNA samples from 69 Italian coke oven workers assayed by DELFIA. The standard curves demonstrated that the limit of detection of 4.0 adducts in 10(8) nucleotides for polycyclic aromatic hydrocarbon-DNA adducts by ELISA, using 35 micrograms of DNA/microtiter plate well, has been decreased to 1.3 adducts in 10(8) nucleotides by DELFIA, using 20 micrograms of DNA/microtiter well. If 35 micrograms of DNA were used in the DELFIA, the calculated detection limit would be 0.7 adducts in 10(8) nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348059 TI - Increased sister chromatid exchange frequencies observed in a cohort of inhabitants of a village located at the boundary of an industrial dumping ground: phase I. AB - Since the mid-eighties, a sand pit located at the boundary of Mellery, a small village in Belgium, has been used as a dumping ground for industrial waste. After a particularly dry summer, many people complained of very foul smells coming from the dumping ground. An analysis of the environmental atmosphere detected alkanes and chlorinated saturated and unsaturated hydrocarbons in various concentrations. Consequently, the Belgian Ministry of the Environment requested additional measurements from the dumping site and the surrounding regions. Given the hazards and possible ill health effects associated with simultaneous exposure to low levels of many chemicals, biomarkers of personal exposure were measured in a representative group of people living in this village. The cytogenetic consequences of daily exposure to a mixture of genotoxicants were measured by the Sister Chromatid Exchange assay. The study included a group of 51 environmentally exposed persons (including 11 children) and 52 controls. A significant increase in Sister Chromatid Exchange frequency was detected among the inhabitants of the village compared to that of the control group, especially among the children living in Mellery as compared to the matched control children. PMID- 8348060 TI - Ornithine decarboxylase and polyamines in colorectal neoplasia and mucosa. AB - Ornithine decarboxylase (ODC) and polyamines are intimately involved in normal cellular proliferation and are likely to play a role in carcinogenesis. ODC activity and polyamine content were measured in tissue samples obtained during colonoscopy from 48 benign neoplastic polyps (20 tubular adenomas; 28 villous adenomas), 18 cancers (including 5 malignant polyps), and adjacent mucosa. ODC activity in polyp and cancer tissue specimens was higher than in adjacent mucosa in 75 and 83% of pairs, respectively. Similarly, putrescine, spermidine, and spermine contents were higher in the majority of polyps and cancers compared to adjacent mucosa. ODC activity and polyamine content in colonic mucosa from 10 patients without a history of colorectal neoplasia were not different from adjacent mucosal values in the patients with neoplasia. In conclusion, ODC and polyamines are elevated in the majority of colorectal neoplasms, but amounts in normal mucosa do not differentiate between patients with cancer, benign neoplastic polyps, and normal subjects. PMID- 8348061 TI - Clinical and laboratory adverse effects associated with long-term, low-dose isotretinoin: incidence and risk factors. The Isotretinoin-Basal Cell Carcinomas Study Group. AB - Adverse effects associated with the long-term low-dose regimens of retinoids used in cancer chemoprevention studies are not well described. In order to examine the clinical and laboratory adverse effects of 3 years of intervention with isotretinoin (10 mg/day) and to assess potential risk factors for developing these, we collected adverse effect data on patients participating in a randomized, placebo-controlled trial designed to evaluate the effectiveness of isotretinoin in preventing the subsequent occurrence of new basal cell carcinoma. Our results showed a significantly higher incidence of adverse mucocutaneous effects and serum triglyceride elevations in the isotretinoin group (P < 0.001). Associated risk factors included male gender, very fair skin, and elevated pretreatment triglyceride levels. The toxicity observed, although less severe and less frequent, was similar to that seen with higher doses and should be weighed with adverse skeletal effects when considering long-term treatment of patients with moderate cancer risk. PMID- 8348063 TI - The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high risk populations: pilot study with cigarette smokers. AB - In preparation for a phase IV lung cancer chemoprevention trial, we conducted a pilot trial of beta-carotene and retinol in high-risk smokers. Eligibility criteria were ages of 50-69 years, a smoking history of at least 20 pack-years, and either being a current smoker or having quit within the past 6 years. Participants were recruited by mailing an interest survey to 29,928 age-selected members of King County Medical Blue Shield. We randomized 1,029 women and men to one of four intervention arms: placebo, retinol, 25,000 international units/day; beta-carotene, 30 mg/day; or retinol plus beta-carotene. Participants were followed for side effects and adherence every 2 months either by a telephone call or a clinic visit. Blood was sampled for retinoid, carotenoid, and liver function analyses annually. beta-carotene and retinol were well tolerated during the follow-up period, which had a median of 1.5 years and a maximum of 3.3 years. Yellowing of the skin was seen in both beta-carotene arms. No differences were seen among arms or over time in incidence or severity of the other 15 monitored symptoms and signs or in serum liver function tests. Adherence was good: 83% of participants remained active on study at 1 year and 75% at 2 years. Serum beta carotene increased from a prerandomization median concentration of 170 to 2100 ng/ml after 4 months of supplementation, and retinyl palmitate median levels more than tripled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348062 TI - The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high risk populations: pilot study with asbestos-exposed workers. AB - Pilot studies are an essential component for major chemoprevention trials. Prior to initiating the multicenter Carotene and Retinol Efficacy Trial to assess the effectiveness of beta-carotene and retinol for preventing lung cancer, we conducted pilot studies in Seattle between 1985 and 1988 in two high risk populations: current and former heavy smokers and asbestos-exposed workers. The Asbestos Workers Pilot Study for the Carotene and Retinol Efficacy Trial demonstrated that recruitment of asbestos-exposed participants with relevant risk factors was feasible from identified sources. We documented negligible toxicity and high adherence with the protocol, schedule, and intervention. Results from the pilot led to extension of the placebo run-in period, changes in the eligibility criteria, improvements in recruitment strategies and scheduling, elimination of stratification by risk factors in randomization, modifications of study vitamin dosage and of side effects monitoring, and refinement of trial design parameters for Carotene and Retinol Efficacy Trial. The Smokers Pilot is reported in the accompanying article (G. E. Goodman et al., Cancer Epidemiol., Biomarkers & Prev., 2: 389-396, 1993). PMID- 8348064 TI - Familial Barrett esophagus and adenocarcinoma of the gastroesophageal junction. AB - Barrett esophagus was found in seven members of a single family. Two of these patients also had adenocarcinoma of the gastroesophageal junction. Among family members who did not have Barrett epithelium, one had esophageal ulcerations with dysplasia in squamous epithelium and another had an esophageal stricture. The pattern of involvement suggests autosomal dominant inheritance of Barrett esophagus and/or gastroesophageal reflux disease in this family, with a strong predisposition for adenocarcinoma of the esophagus. PMID- 8348065 TI - Clinical review on features and cytogenetic patterns in adult acute myeloid leukemia with lymphoid markers. AB - Cytogenetic patterns in correlation with cytologic, biomolecular and clinical findings were studied in 45 adult patients with AML expressing at least one of the following lymphoid associated markers (LM): CD2, CD7, CD10, CD19, CD22, TdT. Four cytogenetic groups were recognized: group I, including 8 patients with 11q23 rearrangements; group II including 5 patients with the Ph chromosome; group III, with 19 patients and aberrations of the "myeloid type" including 4 cases with aberrations of chromosome 13, 3 cases with 1q and 7q anomalies, 2 cases with trisomy 11q; group IV, including 13 patients with normal karyotype. Patients showing extensive lineage infidelity were encountered more frequently in cytogenetic groups I and II than in groups III and IV. Two of 4 cases with aberrations of chromosome 13 showed two or more lymphoid features either at immunophenotyping or at biomolecular analysis of the configuration of lg and TCR genes. Patients with 11q23 rearrangements and with the Ph chromosome were generally young, presented with high WBC count and had low complete remission rate. Survival in Ph chromosome positive patients was uniformly short. We conclude that, although there is no cytogenetic anomaly specific for AML with LM, chromosome findings may be clinically relevant in AML with LM. A morphologic, immunologic and cytogenetic classification of AML with LM may constitute a working basis for future studies aimed at a better definition of clinicopathological features and optimal treatment strategy for these leukemias. PMID- 8348066 TI - Rationale for the clinical use of immunotoxins: monoclonal antibodies conjugated to ribosome-inactivating proteins. AB - The use of chemotherapeutic drugs in combination with bone marrow transplantation to treat cancer patients has markedly improved the disease-free survival and cure rate. Part of the tumor cells, however, can escape from therapy due to resistance. Tumor-specific delivery of toxins that do not interfere with conventional drugs and are not cell cycle dependent seems to be a reasonable approach to overcome this problem. Natural ribosome-inhibiting-proteins (RIPs) from plants, bacteria and fungi which are extremely toxic inhibitors of protein synthesis are isolated and coupled to monoclonal antibodies (MoAbs) and receptor specific ligands, immunotoxins (ITs), to fulfil this purpose. ITs are very suitable to eliminate malignant cells in vitro and in vivo. RIPs contain two or three active sites: a binding site which can be absent in a part of the RIPs and can be replaced by the MoAb; a translocation site that facilitates transport into the cytosol after internalization, and a cytotoxic site that enzymatically inhibits protein synthesis. Binding site containing toxins induce strong nonspecific cytotoxicity when coupled to MoAbs. Recent developments in recombinant DNA techniques enable genetic elimination of the binding site to reduce nonspecific cytotoxicity of these toxins. In this review the structures and mechanisms of action of RIPs as well as factors that influence cytotoxicity of immunotoxins are discussed. Moreover the problems dealing with in vivo application of ITs such as blood clearance by instability of the IT and hepatic entrapment, and production of antibodies directed against MoAb and toxin are reviewed. PMID- 8348067 TI - IgE, Reed-Sternberg cells, and eosinophilia in Hodgkin's disease. AB - Tissues containing Hodgkin's disease tumors of the nodular sclerosis and mixed cellularity subtypes are frequently infiltrated by numerous degranulating eosinophils that release granule proteins such as eosinophil peroxidase and major basic protein. Until recently, the causes of the eosinophil infiltration and degranulation in Hodgkin's disease tumors were unknown. Analysis of Hodgkin's disease tissues by a sensitive and specific immunoperoxidase technique has now demonstrated the extensive presence of IgE in the Reed-Sternberg cells and adjacent cells of Hodgkin's disease tumors. Because eosinophils express a cell surface receptor (CD23) for IgE and degranulate in the presence of IgE deposits, the extensive eosinophilia that is frequently present in Hodgkin's disease tumors is, at least in part, attributable to the IgE deposits within the tumor. In this review, we discuss the possible mechanisms and biological significance of IgE related eosinophilia in Hodgkin's disease. PMID- 8348068 TI - Growth factors of the future. AB - Hematopoietic growth factors stimulate proliferation and enhance functional activity of hematopoietic cells. Erythropoietin, recombinant human (rh) granulocyte colony stimulating factor (CSF), rh granulocyte macrophage CSF and rh interferon have been proven to be a clinically useful therapy. Several other cytokines with other unique effects are being developed for possible clinical usage. The purpose of this manuscript is to review novel uses of current approved cytokines and potential application of experimental growth factors. PMID- 8348069 TI - Second malignancies following treatment in non-Hodgkin's lymphoma. AB - Second malignancies represent an important iatrogenic complication of the treatment of hematologic and other neoplasms. In this review we summarize the literature relating specifically to malignancies developing in the wake of treated non-Hodgkin's lymphoma (NHL). In these patients, the risk of myelodysplastic syndrome (MDS) and acute non lymphocytic leukemia (ANLL) is reported to be increased 10-105 fold over that of the general population. Factors in the development of MDS and ANLL include basic defects in cellular immunity in NHL patients as well as treatment with alkylating agents and low dose total body irradiation. Biologically these secondary MDS and ANLLs are characterized by specific cytogenetic abnormalities and results of treatment are poor. Currently bone marrow transplantation offers the only potential cure. There is no clear statistical evidence that solid tumors occur more frequently after NHL. However, bladder carcinoma, in cyclophosphamide treated patients, and lung cancer have been reported by some to occur with an increased incidence. Further investigation of the molecular events leading to the occurrence of second malignancies in NHL patients and the role played by oncogenes and tumor suppressor genes in this process is still needed. PMID- 8348070 TI - Cerebrospinal fluid neopterin levels in children with central nervous system leukemia. AB - Cerebrospinal fluid (CSF) neopterin levels were determined by high-pressure liquid chromatography in 48 normal children and in 15 children with meningeal relapse of hematologic malignancies (13 acute lymphoblastic leukemia and 2 high grade lymphomas). When meningeal relapse was diagnosed, all patients had CSF neopterin levels higher than mean normal value +2 standard deviations. No significant correlation between the blast count in the CSF and neopterin levels was observed. CSF data before relapse were available in 10 children: the neopterin values at relapse were significantly higher than values observed at diagnosis. In 3 patients, elevated neopterin levels preceded the occurrence of neurologic signs and the detection of blast cells in CSF by 15 to 30 days. In the absence of infection, the rise of CSF neopterin levels in patients with hematologic malignancies indicates an active phase of the disease. This could reflect a cell-mediated immunologic process induced by malignant cells. The measurement of CSF neopterin should be helpful in the monitoring of patients to detect early meningeal relapse. PMID- 8348071 TI - Modalities of in vitro IgM and IgG production by peripheral blood lymphocytes of chronic lymphocytic leukemia patients and healthy volunteers. AB - In vitro spontaneous and mitogen (LPS, rIFN alpha and PWM) or cytokine (rIL-2) induced IgM and IgG production by peripheral blood lymphocytes of 15 CLL patients and 16 healthy volunteers has been determined. This study has shown: (1) that there is no difference between healthy donors and CLL patients in respect to level and variability of spontaneous immunoglobulin production by their lymphocyte cultures; (2) that there is no correlation between the percentage of B cells in individual cell cultures obtained from CLL patients and the amount of spontaneously produced IgM or IgG; (3) that there is a correlation between spontaneous in vitro IgM production and IgM content in the serum of the patient; (4) that in CLL patients selective augmentation of IgM production could be obtained after stimulation with PWM or rIL-2, but only in those cultures which spontaneously produce more than 35 ng/ml of IgM and (5) that the number of lymphocyte cultures able to be stimulated to IgM production is about 10 times smaller when they originate from CLL patients than from healthy volunteers. These findings are in line with the view that B cells in CLL patients often do not differentiate due to the insufficiency of factor(s) secreted by their own activated T-cells, but that in essence they follow the same differentiation pathway as normal B-cells. PMID- 8348072 TI - Classification of Hodgkin's disease biopsies by a panel of four histopathologists. Report of 1,140 patients from the German National Trial. AB - First results from reviewing the diagnostic biopsies of Hodgkin's lymphomas (HL) are reported. Biopsies from 1,140 patients were evaluated by consensus diagnoses according to an extended classification of the British National Lymphoma Investigation. 95 of the recruited cases (8.3%) were omitted and not approved as Hodgkin's lymphoma. The remaining 1,045 biopsies were classified as follows: Lymphocytic predominance 31 (2.7%); Nodular sclerosis (NS) 660 (57.9%), Mixed cellularity (MC) 159 (13.9%); Lymphocytic depletion 8 (0.7%); unclassifiable Hodgkin's 148 (13.0%). The unproved Hodgkin's cases [95 (8.3%)] were divided into non-Hodgkin's lymphomas 32 (1.9%), uncertain due to inadequate techniques 32 (2.8%), borderline between Hodgkin's- and Non-Hodgkin's lymphoma 23 (2.0%). Major dissent on this question involved 17 cases (1.5%) and 1 case which was non malignant. All unclassifiable, borderline or dissent cases were reassessed after the histologic techniques were improved, and immunophenotyping and clinical data reevaluated. The rate of agreement among the observers was about 81.6%, varying between 23.8% in grade 2 NS to 85.0% in both NS groups. Only 62.8% of all primary diagnoses were approved by the final diagnoses of the panel. Important differences in the classification of the British National Lymphoma Investigation concerns the NS-group and mainly its grade 2 subtype. MC was identical in both classifications. Clinico-pathologic correlation of actuarial survival times revealed a significantly worse outcome of MC vs NS, < 20% after 80 months observation. Only slightly significant better survivals were found in grade 1 vs grade 2 NS. Significant differences in unclear compared to all Hodgkin's, were found and the worst survival was in the NHL group. PMID- 8348073 TI - Interleukin 2- and interferon alpha induced natural killer cell activity as a marker of progression in hairy cell leukemia. AB - Hairy cell leukemia (HCL), a rare B-cell chronic lymphoproliferative disorder, is often accompanied by immune abnormalities. A marked impairment of the natural killer cell-mediated cytotoxicity (NK activity) has been reported in most patients at diagnosis. In the present report a long-term follow-up study of NK activity of splenectomized HCL patients is recorded. Among patients who persisted with stable disease two groups, one with normal NK activity, and another with low NK activity, could be recognized. Patients with progressive stage were characterized by a low NK cytotoxic activity. In vitro tests showed that interferon alpha (IFN-alpha) and interleukin 2 (IL2) could increase the NK activity to normal levels only in HCL patients with stable disease, while in progressive HCL these cytokines showed a significantly decreased effect. These results indicate that cytokine-induced NK cytotoxicity appears to be a valuable parameter in assessing the stage of HCL. PMID- 8348074 TI - Disseminated visceral fusariosis treated with amphotericin B-phospholipid complex. AB - Fusariosis, a rare infectious disease of the immunocompromised host, is relatively resistant to amphotericin B (AmB) or other antifungal agents. We describe a 5-year follow-up of a 40 year old woman with T-type acute lymphoblastic leukemia who following chemotherapy developed prolonged high fever, chills, night sweats, and severe weakness. Liver function tests were impaired and abdominal computerized tomography (CT) showed multiple lesions in the liver and abnormal structure of the spleen. A laparotomy revealed multiple granulomas containing Fusarium sp. in the liver, and the spleen was heavily infiltrated by the same fungus. The patient failed to respond to the conventional AmB dosage form (Fungizone) even after a total dose of 3.0 g was given, and developed significant renal impairment. AmB was complexed (in a mole ratio of 1:16) with a mixture of the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (mixed in 7:3 mole ratio). The resulting drug complex, AmB PLC, was then administered (1-4 mg/kg/day, total dose 4.2 g) and subsequently the patient was cured of all symptoms of fusariosis. There were only mild side effects and no nephrotoxicity was evident. On the contrary, marked improvement of the renal function tests occurred during AmB-PLC treatment. Eight months later, she developed a spinal lesion with dense consistency in L5 and S1, and after receiving another course of AmB-PLC (3.1 g) she recovered completely. In a 2 year follow-up period the patient had no further relapse of the fungal disease. Subsequent chemotherapy given for relapse of the leukemia was followed by a new fungal infection, which was treated with AmB-cholesteryl sulfate complex (Amphocil).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348075 TI - HTLV-I associated and non-associated primary T-cell lymphoma of gastrointestinal tract. AB - The gastrointestinal (GI) tract is the common extranodal site for non-Hodgkin's lymphoma (NHL), and primary lymphoma of GI tract are mostly of B-cell origin. We have treated 16 patients with primary lymphoma of GI tract between 1981 and 1991, of whom 10 (62%) were of B-cell origin, while 6 (38%) were of T-cell origin. The incidence of T-cell phenotype in our hospital was considered to be much higher than that of previous reports and these 6 patients with primary T-cell lymphoma of GI tract were carefully studied. The primary sites were stomach in 4, ileocecum in 1, and duodenum in 1 case. Their T-cell nature was confirmed by immunohistochemical methods. All were peripheral T-cell lymphomas; one was CD 3+ 4- 8- and the other 5 were CD 3+ 4+ 8-. The antibody against human T-cell leukemia virus type I (HTLV-I) was positive in 3 cases (HTLV-I associated), but negative in 3 (HTLV-I non-associated). The integration of HTLV-I proviral DNA in HTLV-I associated patients was demonstrated by Southern blot analysis after DNA amplification by means of polymerase chain reaction (PCR). The clinical features of the HTLV-I associated and HTLV-I non-associated primary T-cell lymphoma of the GI tract were quite different. HTLV-I associated patients showed leukemic manifestations and tumor involvement of the skin at a later stage of the disease. These observations indicated that HTLV-I can play an important role in the occurrence of primary T-cell lymphoma of GI tract. PMID- 8348077 TI - Unusual rheumatological and cardiological manifestations of acute myelogenous leukemia in a patient with Klinefelter's syndrome. AB - We report the case of a 40-year-old man with Klinefelter's syndrome who presented with a complex multisystem illness, the predominant manifestations of which were rheumatological and cardiological. This disorder coincided with a diagnosis of acute myelogenous leukemia evolving out of a myelodysplastic syndrome and resolved completely after chemotherapy. It is concluded that the hematological malignancy probably played a causal role in the development of this unusual illness which was likely immunologically mediated. PMID- 8348076 TI - Six Colombian patients with adult T-cell leukemia/lymphoma. AB - Six Colombian patients with adult T-cell leukemia/lymphoma (ATL) are presented. The clinical and hematological features, the familial clusters of human T lymphotropic virus type 1 (HTLV-I) carriers and the prognoses of the Colombian ATL patients were similar to those previously reported for Japanese ATL patients. The only difference was the mean age of onset, which was more than 20 years younger than in Japanese patients. Three patients with ATL were suffering from strongyloidiasis. In one patient it was suggested that ATL developed after horizontal transmission from his wife. In addition, there was a familial case of ATL and HAM/TSP. It seems that in some areas of Colombia, not only HTLV-I infection and HAM/TSP but also ATL are highly endemic. PMID- 8348078 TI - Progression of essential thrombocythemia to blastic crisis via idiopathic myelofibrosis. AB - We report a 61-year-old man with essential thrombocythemia (ET) whose clinical course was followed for 12 years. The ET evolved into true idiopathic myelofibrosis (IM) 6 years after the initial diagnosis and progressed to myeloid blastic transformation 6 years later. The cytogenetic analysis showed a normal karyotype during the ET phase but subsequent analysis revealed an abnormal karyotype during the IM phase which evolved clonally at blastic crisis with constant involvement of chromosome 13q and chromosome 7. The close monitoring of essential events, using clinical, morphologic, immunologic and cytogenetic parameters, allowed us to carefully identify the transition from one chronic myeloproliferative disease (MPD) to another. This is only the second case reported showing a clinical evolution of this nature. The clinical and biological aspects of the disease are briefly discussed. PMID- 8348079 TI - Ultrastructural observations on a variant of acute promyelocytic leukemia. AB - A patient with acute leukemia is presented in whom the leukemic cells, as seen by light microscopy were typical promyelocytes. The cells had normal or slightly invaginated nuclei with typical cytoplasmic granules and the diagnosis was confirmed by cytochemistry. The clinical course was rapid and the patient died of disseminated intravascular coagulation and urosepsis within a few days of diagnosis. However, electron microscopic examination showed cells with extremely convoluted and lobulated nuclei with nuclear pockets and cytoplasmic bridges as well as the complete absence of cytoplasmic granules in the majority of the cells. Furthermore, the urine lysozyme (muramidase) was elevated. These findings suggest that the leukemia in this patient may be classified as a hypogranular variant of acute promyelocytic leukemia (APL), with monocytoid ultrastructural appearances. PMID- 8348080 TI - Identification of a specific pattern of "immediate-early" gene activation induced by estrogen during mitogenic stimulation of rat uterine cells. AB - Estrogen hormones are potent mitogens for certain target tissues, where they stimulate cell growth by inducing recruitment of quiescent cells in cycle and by fostering cell cycle progression. To define the molecular bases of the mitogenic action of these steroid hormones, the pattern of "immediate-early" gene expression was monitored during the early phases of estrogen stimulation of rat uterine cells in vivo. Nuclear run-on transcription and/or Northern blot RNA analysis indicate that c-jun, junB, jun-D, c-fos, TIS 1 (also called NGFI-B or nur/77) and TIS 8 (zif-268, krox24, egr-1, or NGFI-A) genes are all transiently activated in the uterus (up to 20-fold) within 30-120 min after treatment of adult ovariectomized rats with a mitogenic dose of 17b-estradiol. Conversely, JE gene mRNA accumulates progressively in estrogen-stimulated uterine cells, whereas TIS 11 and 21 genes are only slightly responsive to the hormone (less than twofold induction) and fos B,fra-1,fra-2,krox20 (egr-2), TIS 7 and 10, KC, and c rel mRNAs are undetectable in rat uterus either before or after estrogen treatment. Stimulation in the presence of cycloheximide shows that only c-jun, jun-D, c-fos, and JE gene activations are primary responses to the hormone in rat uterine cells. These findings establish the direct mitogenic role of estrogen and identify for the first time a specific genetic program activated by these steroid hormones during stimulation of target cell proliferation. Furthermore, since most of the activated genes encode for transcription factors, these results enable us to envision how the mitogenic signal transmitted by the hormone can be elaborated and amplified within target cells by the products of estrogen-responsive genes, leading to a cascade of growth-dependent gene regulation, cell cycle progression, and, ultimately, cell division. PMID- 8348081 TI - Binding studies of RU486 in different Reuber hepatoma variants. AB - The synthetic steroid RU486, which displays antiprogestin and antiglucocorticoid properties in different systems, inhibits cell growth in dexamethasone-sensitive H56 cells containing glucocorticoid receptors, as well as in dexamethasone resistant S-H56-125 cells displaying a very low level of dexamethasone binding. In order to better understand the mechanism of the antiproliferative effect, the binding of RU486 to these hepatoma cells was examined. Results revealed the presence of two different kinds of binding sites for RU486 in dexamethasone sensitive H56 cells whereas only one type of site was detected in the dexamethasone-resistant cells. These peculiar sites were also recognized by cortivazol during competition experiments. Thus, it seems that S-H56-125 cells contain an altered glucocorticoid receptor that binds RU486 and cortivazol but virtually not dexamethasone. The ability of RU486 to inhibit the growth of dexamethasone-resistant cells suggests this steroid may be used to treat tumor cells that develop glucocorticoid resistance after long-term treatment. PMID- 8348083 TI - [Epidemiologic situation of tuberculosis in the world--actual state, threats and perspectives]. PMID- 8348082 TI - The stereochemistry of the recognition of nitrogen-containing heterocycles by hydrogen bonding and by metal ions. AB - An analysis of the stereochemistry of hydrogen bonding and metal binding to some nitrogen-containing heterocycles found in crystal structure determinations has shown that the interacting atom will generally lie in the plane of the heterocyclic ring system in a direction that approximately bisects the C-N-C angle of the heterocycle. The Cambridge Structural Database (CSD) of crystal structures of small molecules was used for this analysis because stereochemical data are available at high resolution and are amendable to comparative analysis. It was found that, for hydrogen bonding, a slight out-of-plane deviation of the binding atom is marginally more likely than an in-plane deviation. Metal ions appear to bind in a manner that is similar to that of hydrogen bonding to a protonated heterocycle, no matter what the chemical identity of the metal. The binding is more rigid, with less in-plane or out-of-plane deviation of the metal ion compared to the interaction with a hydrogen-bonding group. Some ab initio molecular orbital energy calculations give a measure of the energies involved when metal ions or hydrogen-bonding groups deviate from the plane of the ring system or from the line bisecting the C-N-C angle of the heterocycle. These results are compared with reported structural data (at lower resolution) for some acridine-oligonucleotide complexes and the surroundings of histidine rings in some protein crystal structures. PMID- 8348084 TI - [Evaluation of the epidemiologic situation of tuberculosis and effectiveness of the program for its control in Poland]. PMID- 8348085 TI - [Tuberculosis in the central register for tuberculosis]. AB - Applied methods and results of antituberculosis treatment of all registered patients in 1990 in Poland are presented. Tuberculosis prevention was achieved in 91.9% of sputum-positive patients similarly, diagnostic mistakes were detected in 10% patients with non-bacteriologically determined tuberculosis. In one year since registration 7.7% of sputum-positive patients and 3.9% of patients with non bacteriologically confirmed tuberculosis have been dying in one year since registration time. Majority of patients in Poland were treated too long because of tuberculosis. PMID- 8348086 TI - [Verification of tuberculosis prognosis in Poland to the year 2000]. AB - In 1978 year a tuberculosis prognosis in Poland up to 2000 year was prepared in the Institute of Tuberculosis and Lung Diseases in Warsaw, according to epidemiological and epidemiologic-metric model (efficacy of "diagnosis-therapy program" from 60 to 90% and efficacy of BCG vaccination to 60%). The aim of study was to compare epidemiological data for registered tuberculosis cases in 1980 1990 (incidence morbidity and mortality) with the same parameters presented in prognosis for 1980-1991). Efficacy of analyzed programme was similar to predicted values: for incidence of tuberculosis-64%, for morbidity-65% and for mortality 66%. PMID- 8348087 TI - [Case finding program for tuberculosis with special reference to chest x-ray examination]. AB - An analysis of tuberculosis case-finding programme in Poland in 1966-1991 was performed. The main methods applied in practice were--case-finding according to "symptoms" and according to results of "chest x-ray examination". About 90% of new cases were detected by above mentioned methods. Case-finding according to "symptoms" was increasing parallel to age of patients and reached 74% in group over 60 years. On the other hand, the efficacy of chest x-ray examination was decreasing parallel to age of patients one was calculated as 19%. The case finding method according to "symptoms" is suggested by authors as a basic and useful, especially in family doctor's practice. Chest x-ray examinations should be limited to high risk population. PMID- 8348088 TI - [Drug sensitivity of bacillus strains M. avium-intracellulare (MAIC), M. kansasii cultured from patients with mycobacteriosis before treatment]. AB - The aim of study was to evaluate a drug sensitivity of M. avium-intracellulare, M. xenopi and M. kansasii cultured from 55 patients with mycobacterioses. The identification of strains was performed with morphological and biochemical tests and thin-layer chromatography. Resistance tests were done on egg L-J and agar media for selected drugs. It was documented that MAIC strains were non-sensitive on isoniazid and rifampicin, and other ones. The most active drug was cycloserine inhibiting growth of 80% but rifabutine--50% of strains. M. xenopi strains were sensitive for tested drugs including isoniazid and rifampicin (about 30%). M. kansasii strains were in 100% sensitive for cyclosporine, rifabutine, Davercin and ofloxacin and partly for isoniazid, streptomycin and Augmentin. PMID- 8348089 TI - [Analysis of drug sensitivity of M. tuberculosis strains isolated from patients treated for tuberculosis in 1982-1991]. AB - Analysis of drug-sensitiveness of 822 M. tuberculosis strains isolated from patients with pulmonary tuberculosis treated in the Institute of Tuberculosis and Lung Diseases and in Pediatric Clinic of Medical Academy in Warsaw in 1982-1991 years was performed for isoniazid (INH), streptomycin (SM), rifampicin (RMP) and ethambutol (EMB). Drug sensitivity test was done on a basis of complexed proportional method according to Conethi and resistance index method according to Mitchinson. Examined strains were determined as resistant when the resistance index was 4 for INH, SM. RMP and EMB. During analysis the increase of resistance strains percentage (mean 25%) was observed in sputum-positive tuberculosis patients hospitalized in the Institute of Tuberculosis and Lung Diseases. The highest number of resistant strains was noticed in relation to CNH and RMP. PMID- 8348090 TI - [Coexistence of pulmonary tuberculosis and alcoholism in Poland]. AB - The aim of study was to determine a number of alcoholics in new diagnosed cases of bacteriological confirmed pulmonary tuberculosis in 1989-1990. Data were obtained from the Central Register of Tuberculosis. It was found that the number of alcoholics among new registered patients with tuberculosis increased from 8.8% to 10.5%. Young patients were more than 60% group. Results of treatment of severe types of pulmonary tuberculosis in alcoholics were also not so effective as in typical patients. PMID- 8348091 TI - [Tuberculosis as a cause of death in patients treated in the institute of tuberculosis in 1976-1991]. AB - This study aimed at assessing the reasons why tuberculosis-which can be successfully treated today-is still the cause of death in some patients treated at the Institute of Tuberculosis in the last 15 years. The material consisted of clinical documentation and the results of autopsy of 30 patients who died of tuberculosis between 1976-1991. It was found that 19 out of 30 patients were not treated with antituberculous drugs or were treated only during few days because tuberculosis was diagnosed too late (in 15 patients after death). In 6 patients the treatment failed due to side effects of drugs and in 5 immunosuppressed patients, disease progressed despite the treatment. Difficulties in tuberculosis diagnosis were caused by atypical appearance of the disease in the chest X-ray (localization in the middle and lower lobes in 15 cases, absence of cavities in 22 cases) and in the extrapulmonary regions (11 cases). The main obstacle was the failure to cultivate tubercle bacilli from numerous specimens of the sputum in 10 out of 23 patients in whom the cultures were done. PMID- 8348092 TI - [Tuberculosis found in autopsies done in the Institute of Tuberculosis and Lung Diseases 1972-1991]. AB - Between years 1972 and 1991 1500 autopsies were done in the Institute of Tuberculosis and Lung Diseases in Warsaw. Active tuberculosis was found in 119 cases (7.9%). 56 patients died of tuberculosis. Tuberculosis was not diagnosed during life in 37% of all cases and in 39% of that in whom it was the cause of death. Tuberculosis was undiagnosed significantly more often in the years 1982 1991 than in years 1972-1981. Tuberculosis was restricted to the lungs in 60.5% of cases, was found in the lungs and in the extrapulmonary sites in 37.8% and only outside lungs in 1.7%. This is in contrast with official polish statistics. The extrapulmonary tuberculosis was registered in only 4% of cases. PMID- 8348093 TI - [Tubercular meningitis and encephalitis in adults--own experience]. AB - Diagnostic, clinical and therapeutical problems of tuberculous meningitis and encephalitis have been discussed on a basis of clinical observation of 67 patients. In the early phase of disease the diagnosis is based on clinical parameters and results of cerebrospinal fluid examinations. Authors suggest a shortage of time treatment under 12 months. PMID- 8348094 TI - [Mycobacterial infection in patients with AIDS]. AB - Bacteriological diagnosis of tuberculosis was performed in 104 HIV-positive patients, in majority AIDS patients hospitalized in AIDS Clinic of Infections and Parasitic Diseases Institute of Medical Academy. 390 samples were examined, e.d. 3.75 from each patient (from 1 to 22 samples). M. Tuberculosis was diagnosed in 14 patients and all of them were clinically observed because of pulmonary tuberculosis. The highest percentage of positive results was obtained from bronchial fluid evacuated during bronchoscopy. PMID- 8348095 TI - [Two cases of tuberculous pericarditis--diagnostic difficulties]. AB - Some difficulties etiological diagnosis were presented in an example of two clinical cases. In the first patient with exudative pericarditis tuberculosis was determined in histopathological examination of lymph node (caseous necrosis). After antituberculotic treatment the majority of clinical symptoms was disappeared. In the second patient with chronic constrictive pericarditis the tuberculous etiology was accepted according to highly positive tuberculin reaction and signs of pericardial calcification. Patient was qualified to pericardiectomy. PMID- 8348096 TI - [Difficulties in interpreting values for PaO2, PaCO2 and pH values in arterialized capillary blood--case report]. AB - Measurements of PaO2, PaCO2 and pH in arterialized capillary blood in patient with angiogenic disturbances in upper and lower extremities were out of value. Correct evaluation above mentioned parameters was possible only in arterial and arterialized earlobe blood. PMID- 8348097 TI - [Difficulties in diagnosing a case of chronic necrotic aspergillosis with an unfavorable course]. AB - A case of chronic necrotic aspergillosis was discussed. Diagnostic and therapeutic difficulties were described in patient with an insufficiency of immune response mainly in polymorphonuclear leukocytes function. PMID- 8348098 TI - [Microbiological diagnosis of tuberculosis and lung diseases in the last 30 years]. PMID- 8348099 TI - [Role of the social committee against tuberculosis and lung diseases and the program for prevention of tuberculosis]. PMID- 8348100 TI - [Grzegorz Bagdasarian (28.VII.1902-21.X.1991)]. PMID- 8348101 TI - Consensus conference on measles. PMID- 8348102 TI - Food poisoning involving a chemical product--Quebec. PMID- 8348104 TI - Potential danger of placing dry ice into a commercial plastic screwcap biohazard safety shipping container. PMID- 8348103 TI - Decline in Haemophilus influenzae type B invasive infections at five Canadian pediatric centres. PMID- 8348105 TI - HIV antibody detection in oral fluids. PMID- 8348107 TI - Calcium phosphates in pharmaceutical tableting. 2. Comparison of tableting properties. AB - Ten calcium phosphates suitable for direct compression (dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydrous and hydroxylapatite) were investigated with respect to their compressional behaviour. Except for Di-Cafos A all products gave tablets with sufficient to good mechanical strength. Nevertheless, there were differences between the products. All tablets prepared from the different products showed a high friability. This seems to be a problem of the calcium phosphates in general. On the other hand, the influence of magnesium stearate on the mechanical strength of the tablets was negligible for all products investigated. Moreover, a considerable effect of the particle size on the tensile strength of the tablets was found. The ejection forces and residual pressures were high in general, but critical only in the case of hydroxylapatites. Heckel plots were used to differentiate between plastic deformation and brittle fracture of the particles. In the case of calcium phosphates the slope of the Heckel plots indicated the hardness of the particles rather than their deformation behaviour. PMID- 8348106 TI - Calcium phosphates in pharmaceutical tableting. 1. Physico-pharmaceutical properties. AB - Ten commercially available calcium phosphates used for direct tableting were evaluated. The particle size distributions, powder properties, sorption isotherms and pH values of aqueous slurries were compared. All samples showed good or at least sufficient flowability. Scanning electron micrographs illustrated the different kinds of manufacturing and gave hints on their expectable behaviour under compaction pressure. The sorption isotherms of identical chemical substances, which had been manufactured by different methods, differed strongly. This can be related to their specific surface areas. Most of the hydroxylapatites have large surface areas and can absorb up to more than 15% water at 93% relative humidity. Dibasic calcium phosphate dihydrate was non-hygroscopic and absorbed less than 1% water. With the exception of monobasic calcium phosphate monohydrate all calcium phosphates behaved quite neutral in water. Monobasic calcium phosphate monohydrate can be regarded as a solid acid. Although the calcium phosphates are usually stable substances, the role of crystal water in the case of dibasic calcium phosphate dihydrate and monobasic calcium phosphate monohydrate is problematic due to possible interactions with active ingredients. PMID- 8348108 TI - Kinetics and mechanism of the degradation of 1a-acetylmitomycin C in aqueous solution. AB - The acid-catalyzed degradation of mitomycin C is supposed to be governed, to a certain extent, by the protonation status of the aziridine nitrogen in the molecule as well as the protonation degree of the opened aziridine function in a key intermediate species, formed during mitomycin degradation. In order to obtain information about the contribution of the protonation degrees of these functions in controlling the degradation processes, we investigated the degradation of 1a acetylmitomycin C in acidic aqueous solutions. In the presence of 0.001 mol/l phosphate buffers five 1-hydroxy and mono-acetyl mitosenes are formed, whereas in 1.0 mol/l acetate buffers a total of eight products could be identified, two of them being diacetyl mitosenes. Over the whole pH range studied the formation of 1,2-Z-mitosenes prevails, indicating that, contrary to mitomycin C, a pH independent factor controls the ultimate 1,2-stereochemistry. PMID- 8348109 TI - The use of hypoglycaemic and cardiovascular drugs in 582 patients with diabetes mellitus. Description and quality assessment. AB - The medication of 582 patients taking insulin or oral hypoglycaemic agents has been analysed. A characterization is given of the patients and their antidiabetic medication. Subsequently, a description of the use of cardiovascular drugs, in comparison with an age-matched control group, is presented. The diabetic population investigated has an average age of 67 years. Most cardiovascular agents, with the exception of thiazide diuretics, are used to a larger extent in the diabetic group in comparison with the control group. Non-selective beta blockers, possibly hazardous in patients with diabetes mellitus, appear to be prescribed without restriction in the diabetic patients investigated. The results of this study suggest that the choice of drugs for the treatment of cardiovascular co-morbidity in patients with diabetes mellitus can be improved. PMID- 8348110 TI - Randomized double-blind study of nabumetone and piroxicam in the treatment of osteoarthritis in Dutch general practice: efficacy and tolerability. AB - To study nabumetone (1,000 mg once daily) by comparison with piroxicam (20 mg once daily) in patients with osteoarthritis, a randomized, double-blind trial was set up in 40 general practices. Evaluation was based on clinical outcome in 198 patients. There was some evidence that nabumetone is associated with a lower and less severe occurrence of gastric pain, and with more withdrawals due to lack of efficacy. Although the differences between nabumetone and piroxicam were small in this study, these were clinically relevant. The general practitioner should balance the respective benefits of greater safety and tolerance against greater efficacy in meeting the requirements of an individual patient with osteoarthritis. PMID- 8348111 TI - Effect of pH on absorption of sufentanil citrate in a portable pump reservoir during storage and administration under simulated epidural conditions. AB - Sufentanil (5 micrograms/ml as citrate) was investigated for its stability when diluted with sodium chloride 0.9%, in 100 ml polyvinyl chloride portable pump reservoirs during administration under simulated epidural conditions at 32 degrees C for 48 h. Sufentanil was absorbed into the polyvinyl chloride, resulting in a reduction of 10.9% of the concentration after 48 h. The absorption of sufentanil (5 micrograms/ml as citrate), alone and in combination with bupivacaine hydrochloride (2 mg/ml), was investigated when diluted with sodium chloride 0.9% in combination with a citrate buffer (pH 4.6), in the same reservoirs under similar conditions. There was no loss of sufentanil after 48 h in both experiments. The effect of the pH on the absorption of sufentanil in polyvinyl chloride was investigated at different pH values. After storage for 21 days at 32 degrees C there was 5.1% loss of sufentanil at pH 4 and 80.6% loss at pH 6. The citrate buffer at the optimum pH (4.6) has a low, acceptable buffer capacity for epidural administration. PMID- 8348112 TI - Quality of life 3. Rheumatoid arthritis. AB - It has increasingly been recognized that for the evaluation of interventions in patients with rheumatoid arthritis not only physician-oriented variables, like laboratory or radiographic assessments but also patient-oriented variables such as quality of life are of importance. Many different arthritis-specific quality of life instruments have been developed in recent years using different or no definition at all about the concept 'quality of life'. In this review a generally accepted definition of quality of life, existing of three components, is presented. The interrelationship between quality of life and all the different variables used in assessing disease activity in rheumatoid arthritis is discussed. PMID- 8348113 TI - Direct gradient reversed-phase HPLC analysis and preliminary pharmacokinetics of nalidixic acid, 7-hydroxymethylnalidixic acid, 7-carboxynalidixic acid, and their corresponding glucuronide conjugates in humans. AB - A gradient reversed-phase high pressure liquid chromatographic analysis was developed for the direct measurement of nalidixic acid with its acyl glucuronide, 7-hydroxymethylnalidixic acid with its acyl and ether glucuronides, and 7 carboxynalidixic acid in human plasma and urine. The glucuronides and 7 carboxynalidixic acid were not present in plasma after an oral dose of 1,000 mg nalidixic acid. The acyl glucuronides of 7-carboxynalidixic acid were not present in plasma and urine. The acyl glucuronides are stable in urine at pH 5.0-5.5. The subject's urine must therefore be acidified by the oral intake of 4 x 1 g of ammonium chloride per day. With acidic urine, hardly any nalidixic acid was excreted unchanged (0.2%). It was excreted as acyl glucuronide (53.4% of dose), 7 hydroxymethyl-nalidixic acid (10.0%), the latter's acyl glucuronide (30.9%), and 7-carboxynalidixic acid (4.2%). PMID- 8348114 TI - Effects of catechins on the mouse lung carcinoma cell adhesion to the endothelial cells. AB - We studied the effects of 5 kinds of catechins on the adhesion of mouse lung carcinoma 3LL cells to the monolayer of bovine lung endothelial cells. (-) Epicatechin gallate and (-)-epigallocatechin gallate were active in inhibiting the 3LL cell adhesion, while (+)-catechin and (-)-epicatechin were inactive. (-) Epigallocatechin showed a considerable cytotoxicity. These data suggest that the specific chemical structure is required to exert the inhibitory activity of catechins and the search for the cellular binding protein(s) bound to these inhibitory catechins would provide a clue to clarify the mechanism of interactions between tumor cells and endothelial cells. PMID- 8348115 TI - A cell cycle study of human mammary epithelial cells. AB - The growth regulation of human mammary epithelial cells (HMEC) cultured in a growth factor/hormone-enriched (e.g. EGF, insulin) medium with bovine pituitary extract as the only undefined supplement was studied. The doubling times of the cultures, in which the cells appear in colonies, was 55-72 h, and a considerable intercolonial heterogenecity in proliferative activity could be demonstrated. However, every colony, irrespective of the size of the growth fraction, comprised a sub-population of rapidly growing cells which had a mean generation time of approximately 22 h. When insulin was removed from the culture medium, HMEC proliferation was inhibited. This growth inhibition was shown to be a result of a cell cycle-specific block. PMID- 8348116 TI - Movement of cell-associated matrix during contact competition of cells in mixed cultures. AB - Co-cultured contacting heterotypic cell groups compete with one another for the attachment to the substratum. In the course of this competition one cell group can progressively push another from the substratum. Alterations to the distribution of cell-associated matrix structures in the course of contact competition were examined by immunomorphological methods in the paired cultures of two epithelial lines and those of fibroblasts and epithelia. It was found that matrix structures formed by the retreating cells withdrew from the substratum simultaneously with the cells. These results show that two forms of matrix structures should be distinguished: the usually immovable matrix upon which the cells crawl and the movable matrix that the cells carry with them when they move. PMID- 8348117 TI - The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid. AB - The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg/body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism. PMID- 8348118 TI - Suppression of DNA synthesis and induction of apoptosis in rat prostate by human seminal plasma inhibin (HSPI). AB - In vivo administration of HSPI (10.7 kDa FSH suppressing peptide of prostate) to intact adult male rats was found to suppress the basal levels of incorporation of 3H-thymidine into DNA of ventral and dorsolateral lobes of the prostate, in a dose-dependent manner. Interestingly, microscopic examination of the prostate histology of HSPI treated rats revealed a significantly increased incidence of apoptotic bodies which are indicative of cell death. In another experiment, HSPI was also found to suppress the active DNA synthesis in testosterone-induced regrowth of prostate in castrated rats. Thus HSPI can suppress the basal and stimulated DNA synthesis and also induce apoptotic cell death in rat prostate. PMID- 8348119 TI - In patients with common variable immunodeficiency, interleukin-6 and expression of its receptor on B-cells are normal. AB - In a group of patients suffering from common variable immunodeficiency (CVID), levels of interleukin-6 (IL6) were measured and found to be in the normal range or even increased, for single patients. IL6 production of peripheral blood mononuclear cells was shown to be in the normal range when corrected for monocyte number. To exclude the possibility that the Interleukin-6 receptor (IL6R) on B cells is missing, its expression was measured by assessing the binding of a Phycoerythrin-derivative of IL6 by flow cytometry and correlated with various markers for B-cells and T-cells. As compared with normal controls, no statistically significant deviation of the group as a whole nor for individual patients could be shown. It was concluded that lack of B cell differentiation in the presence of normal to high IL6 as shown for these patients is not due to inability of the B cells to detect IL6 in the serum. PMID- 8348120 TI - Association of plasmid pKT3 with cock spermatozoa in two different temperatures. PMID- 8348121 TI - Influence of recombinant bovine cytokines on proliferation of a bovine mammary epithelial cell line. PMID- 8348122 TI - A linear vector carrying human telomeres is replicated in unfertilized eggs of Xenopus laevis. PMID- 8348123 TI - Characterization of the major cytosolic glutathione transferase in two monkey kidney derived cell lines. PMID- 8348124 TI - The changing face of family care. PMID- 8348125 TI - Home management. Viability and liability. PMID- 8348126 TI - Cost cutting is out of place. PMID- 8348128 TI - The essence of aromatherapy. PMID- 8348127 TI - Safety first at bathtime. PMID- 8348129 TI - Visual care in old age. PMID- 8348130 TI - The painful truth. PMID- 8348131 TI - Volunteers across the years. PMID- 8348132 TI - As I was saying.... PMID- 8348133 TI - The personal cost of caring. PMID- 8348134 TI - Call systems. The solution's as clear as a bell. PMID- 8348135 TI - Functional anatomy of the shoulder complex. AB - Recent research findings are incorporated in this review of the functional anatomy of the shoulder complex. The scapulothoracic mechanism is described, including a review of scapular motion and the structure and function of the sternoclavicular and acromioclavicular joints. New information regarding the resting position of the scapula on the thorax and the effect of aging and spinal posture on position has been presented. In the second part of the paper, the anatomy of the glenohumeral joint is reviewed, with emphasis on the articular, periarticular, and muscular mechanisms responsible for stability of this articulation. The article concludes with a discussion of the integrated function of the scapulothoracic and glenohumeral articulations in upper extremity elevation. PMID- 8348136 TI - Applied MRI anatomy of the shoulder. AB - Magnetic resonance imaging (MRI) of the shoulder is rapidly evolving as the choice diagnostic procedure for management of shoulder derangement, particularly for soft tissue injuries not well delineated by conventional radiography. With application of appropriate MRI protocol/sequences and familiarity with applied shoulder MRI anatomy, valuable diagnostic information may be derived that can greatly assist management/therapy of common problems, such as rotator cuff tears, impingement, and instability as well as less frequent causes of shoulder pain and dysfunction. PMID- 8348137 TI - Neurovascular injuries to the shoulder. AB - The throwing athlete is at risk for neurovascular injuries of the shoulder because of the excessive demands placed upon the shoulder by repetitive throwing motions. The most commonly recognized neurovascular compression syndromes are axillary artery occlusion, effort thrombosis, quadrilateral space syndrome, and thoracic outlet syndrome. Diagnosis is aided by the use of the Adson's test, costoclavicular maneuver, and hyperabduction maneuver. Initial treatment usually is nonoperative. Anticoagulation or thrombolytic therapy can be used for vascular occlusion. Surgery usually is reserved for patients suffering acute or chronic symptoms despite nonoperative treatment. With proper treatment, most patients are able to resume their previous athletic activities in a timely manner with minimal disability. PMID- 8348138 TI - Current concepts in the rehabilitation of the athletic shoulder. AB - The rehabilitative process of the overhead athlete represents a significant challenge to the clinician. Overhead athletes (thrower, tennis player, swimmer) repetitively subject their shoulder joints to high microtraumatic stresses that, due to the accumulative effects, may lead to a variety of shoulder injuries. This type of athletic patient exhibits uniquely specific physical characteristics, such as hypermobility of the anterior shoulder capsule, excessive external rotation, hypomobility of the posterior capsule, limited internal rotation, and generalized ligamentous laxity of the glenohumeral joint. However, the overhead athlete must exhibit functional stability for pain-free sports participation. Functional stability is accomplished through the proficient balance of static (passive) and dynamic (active) stabilizers. During the rehabilitation process, various concepts, such as neuromuscular control, proprioception, force couple efficiency, plyometrics, eccentrics, and scapular stability, can enhance dynamic functional stability for the overhead athlete. The evaluation and treatment of the shoulder patient is in perpetual change, and the purpose of this paper is to discuss several current concepts in the rehabilitative treatment of the athletic shoulder patient. PMID- 8348139 TI - Clinical examination of the shoulder complex. AB - A comprehensive and systematic approach to physical examination of the shoulder is described, with particular emphasis on findings pertinent to an athletic population. The format consists of initial impression, inspection, palpation, range of motion and strength testing, stability assessment, special tests, vascular examination, and general physical examination. PMID- 8348140 TI - The role of the scapula. AB - The scapular musculature is often neglected in designing a rehabilitation protocol for the shoulder. Weakness of the scapular stabilizers and resultant altered biomechanics could result in: 1) abnormal stresses to the anterior capsular structures of the shoulder, 2) increased possibility of rotator cuff compression, and 3) decreased performance. This article presents known facts about the biomechanics of the scapula and surrounding muscles and suggests methods for evaluation of scapular muscle weakness. Exercise techniques to maximally strengthen the scapular musculature are also described. As our ability to document strength of these muscles improves, we will be able to determine the effect of scapular strengthening on improving symptoms related to impingement and instability. Scapular strengthening exercises are usually nonstressful to the rotator cuff and are easily implemented into a rehabilitation program for the shoulder. PMID- 8348141 TI - Pushing the brain initiative. PMID- 8348142 TI - Gene therapy on the Sly. PMID- 8348143 TI - Trinucleotide repeat instability: when and where? PMID- 8348144 TI - Erythropoietin receptor mutations and Olympic glory. PMID- 8348145 TI - Genomic imprinting and gene activation in cancer. PMID- 8348146 TI - Angiotensinogen: a candidate gene involved in preeclampsia? PMID- 8348147 TI - Enhanced Fmr-1 expression in testis. PMID- 8348148 TI - Transgenic mice containing a human heavy chain immunoglobulin gene fragment cloned in a yeast artificial chromosome. AB - We have developed a method for the introduction of yeast artificial chromosomes (YACs) into transgenic mice. An 85 kilobase (kb) fragment of the human heavy chain immunoglobulin gene was cloned as a YAC, and embryonic stem cell lines carrying intact, integrated YACs were derived by co-lipofection of the YAC with an unlinked selectable marker. Chimaeric founder animals were produced by blastocyst injection, and offspring transgenic for the YAC were obtained. Analysis of serum from these offspring for human heavy chain antibody subunits demonstrated expression of the YAC-borne immunoglobulin gene fragment. Co lipofection may prove to be a highly-successful means of producing transgenic mice containing large gene fragments in YACs. PMID- 8348149 TI - Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. AB - Mice with the recessive motheaten (me) or the allelic viable motheaten (mev) mutations express a severe autoimmune and immunodeficiency syndrome. We have shown that the basic defect in these mice involves lesions in the gene which encodes haematopoietic cell phosphatase (HCP). These mice thus provide excellent models for investigating the roles of phosphatases in haematopoiesis and the nature of the genetic and cellular events linking impaired haematopoiesis to severe immunodeficiency and expression of systemic autoimmunity. PMID- 8348150 TI - Direct detection of novel expanded trinucleotide repeats in the human genome. AB - Expansion of trinucleotide repeats can give rise to genetic disease. We have developed a technique, repeat expansion detection (RED), that can identify potentially pathological repeat expansion without prior knowledge of chromosomal location. Human genomic DNA is used as a template for a two-step cycling process that generates oligonucleotide multimers when expanded trinucleotide sequences are present at the level found in myotonic dystrophy and fragile-X patients. We have identified at least one new locus exhibiting trinucleotide expansion. Analysis of three families transmitting a long CTG repeat shows that the allele in these families corresponds to a locus on chromosome 18. RED constitutes a powerful tool to identify other diseases caused by this mechanism, particularly diseases associated with anticipation. PMID- 8348151 TI - Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion. AB - We demonstrate here that somatic variation of CGG repeat length is based on a mosaic of cells with different but stable FMR-1 alleles and does not reflect permanent mitotic instability. The length of a particular allele in an individual cell was maintained in progeny cells establishing a clone. The mutation patterns of multiple repeats in the DNA of fetal tissues were identical and did not significantly change during proliferation in vitro. It is proposed that genotype mosaicism and expansion to full mutation are generated post-conceptionally by the same molecular mechanism in a particular window of early development. PMID- 8348152 TI - The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. AB - Fragile X syndrome is characterized at the molecular level by amplification of a (CGG)n repeat and hypermethylation of a CpG island preceeding the open reading frame of the fragile X gene (FMR-1) located in Xq27.3. Anticipation in this syndrome is associated with progressive amplification of the (CGG)n repeat from a premutation to a full mutation through consecutive generations. Remarkably, expansion of the premutation to the full mutation is strictly maternal. To clarify this parental influence we studied FMR-1 in sperm of four male fragile X patients. This showed that only the premutation was present in their sperm, although they had a full mutation in peripheral lymphocytes. This might suggest that expansion of the premutation to the full mutation in FMR-1 does not occur in meiosis but in a postzygotic stage. PMID- 8348154 TI - Correction of lysosomal storage in the liver and spleen of MPS VII mice by implantation of genetically modified skin fibroblasts. AB - Genetic defects of lysosomal hydrolases result in severe storage diseases and treatments based on enzyme replacement have been proposed. In mice lacking beta glucuronidase, which develop a disease homologous to human mucopolysaccharidosis type VII (Sly syndrome), we have used autologous implants of genetically-modified skin fibroblasts for the continuous in vivo production of the enzyme. The human beta-glucuronidase cDNA was introduced with a retroviral vector into mutant mice skin fibroblasts grown in primary culture. Fourteen mutant mice were implanted intraperitoneally with these modified cells embedded into collagen lattices. All animals expressed beta-glucuronidase from the vascularized neo-organs that developed after implantation and accumulated the enzyme in their tissues. A complete disappearance of the lysosomal storage lesions was observed in their liver and spleen. PMID- 8348155 TI - Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1. AB - We have mapped the autosomal sex reversal locus, SRA1, associated with campomelic dysplasia (CMPD1) to 17q24.3-q25.1 by three independent apparently balanced de novo reciprocal translocations. Chromosome painting indicates that the translocated segment of 17q involves about 15% of chromosome 17 in all three translocations, corresponding to a breakpoint at the interphase between 17q24 q25. All three 17q breakpoints were localized distal to the growth hormone locus (GH), and proximal to thymidine kinase (TK1). Due to the distal location of the breakpoints, previously mentioned candidate genes, HOX2 and COL1A1, can be excluded as being involved in CMPD1/SRA1. The mouse mutant tail-short (Ts) which maps to the homologous syntenic region on mouse chromosome 11, displays some of the features of CMPD1. PMID- 8348153 TI - Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. AB - The expression of the FMR-1 gene, which is implicated in fragile-X syndrome was investigated in human fetuses by in situ hybridization. In 8 and 9 week-old fetuses, FMR-1 mRNAs are expressed in proliferating and migrating cells of the nervous system, in the retina, and in several non-nervous tissues. In the brain of 25 week-old fetuses, FMR-1 mRNAs are produced in all nearly differenciated structures, with the highest level in cholinergic neurons of the nucleus basalis magnocellularis and in pyramidal neurons of hippocampus. The early transcription of FMR-1 gene and the distribution of FMR-1 mRNAs in human fetuses suggest that alterations of FMR-1 gene expression may contribute to the pathogenesis of fragile-X syndrome and especially the mental retardation. PMID- 8348156 TI - A cosmid contig and high resolution restriction map of the 2 megabase region containing the Huntington's disease gene. AB - The quest for the mutation responsible for Huntington's disease (HD) has required an exceptionally detailed analysis of a large part of 4p16.3 by molecular genetic techniques, making this stretch of 2.2 megabases one of the best characterized regions of the human genome. Here we describe the construction of a cosmid and P1 clone contig spanning the region containing the HD gene, and the establishment of a detailed, high resolution restriction map. This ordered clone library has allowed the identification of several genes from the region, and has played a vital role in the recent identification of the Huntington's disease gene. The restriction map provides the framework for the detailed analysis of a region extremely rich in coding sequences. This study also exemplifies many of the strategies to be used in the analysis of larger regions of the human genome. PMID- 8348157 TI - A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews. AB - Fanconi anaemia is an autosomal recessive disease for which four known complementation groups exist. Recently, the gene defective in complementation group C (FACC) has been cloned. In order to determine the fraction of Fanconi anaemia caused by FACC mutations, we used reverse transcription PCR and chemical mismatch cleavage (CMC) to examine the FACC cDNA in 17 FA cell lines. 4/17 patients (23.5%) had mutations in this gene. Two Ashkenazi-Jewish individuals were homozygous for an identical splice mutation. Three additional Jewish patients bearing this allele were found upon screening 21 other families. We conclude that a common mutation in FACC accounts for the majority of Fanconi anaemia in Ashkenazi-Jewish families. PMID- 8348159 TI - International Continence Society. 23rd annual meeting, Rome, Italy, 8-11 September 1993. Abstracts. PMID- 8348158 TI - Microsatellite mapping of a gene affecting horn development in Bos taurus. AB - The presence or absence of horns in Bos taurus is thought to be under the genetic control of the autosomal polled locus, characterized by two alleles: P dominant over p, and causing the polled or hornless phenotype. We have demonstrated genetic linkage between the polled locus and two microsatellite markers, GMPOLL-1 and GMPOLL-2, and have assigned the corresponding linkage group to bovine chromosome 1. This confirms the existence of the postulated polled locus and the hypothesized inheritance pattern. It will allow marker assisted selection for the polledness trait in breeding programs and is a first step towards positional cloning and molecular study of a gene that has been subjected to both natural and artificial selection. PMID- 8348160 TI - An overview of the development of infertility research and treatment. AB - Before the invention of the microscope, knowledge of the anatomic factors in human reproduction was limited to the approximations available to the naked eye. Van Leeuwenhoek developed the microscope and also discovered the spermatozoa. With the availability of microscopy, and later biochemistry, the corpus luteum was described and the endocrine functions of the ovaries were partially elucidated. In recent times, too, imaging--by x-ray, sonography, and MRI, and through the laparoscope--has been the key to advances in our understanding of reproduction and, thus, of infertility and its treatment. PMID- 8348161 TI - Obesity affects circulating estradiol levels of premenopausal hirsute women receiving leuprolide acetate depot. AB - OBJECTIVE: To investigate the effect of premenopausal obesity on circulating levels of estradiol, estrone, free testosterone, androstenedione, DHEAS, and immuno- and bioactive FSH and LH. SETTING: University clinic. PATIENTS AND INTERVENTIONS: Premenopausal hirsute women, four obese and four nonobese, received leuprolide acetate depot [LD in monthly injections (7.5 mg, i.m.)] until estradiol levels decreased to menopausal values; single monthly injections of 15 and then 22.5 mg LD were given if estradiol remained higher than menopausal after 3 months. RESULTS: Estradiol levels of nonobese women reached menopausal values with the 7.5-mg dose, and those of obese women were not significantly reduced with any LD dose. Estrone declined to menopausal levels with 7.5 mg LD, while free testosterone and androstenedione were diminished with 7.5 mg, but not further with 15 or 22.5 mg. Bioactive LH and the bioactive/immunoactive LH ratio were maximally suppressed with 7.5 mg LD; however, LD did not change bioactive FSH levels or the bioactive/immunoactive FSH ratio. These findings were not related to adiposity. CONCLUSIONS: Premenopausal obesity affects circulating estradiol levels of hirsute women receiving LD. The effect does not reflect weight-related differences in circulating levels of androgens or bioactive gonadotropins. Premenopausal adiposity in hirsute women may influence the estrogenic milieu associated with desensitization to GnRH. PMID- 8348162 TI - Confidentiality and American semen donors. AB - Most American donor insemination programs include a policy of complete confidentiality concerning the donor of the semen. This is the result of a long legal tradition of American constitutional law. However, some slight abridgement of this body of legal decisions might be very much in the best interests of children arising from donor insemination, and even--in most cases, in fact--the donors themselves. With regard to the children, the factors involved are both those of genetic counseling, should the need arise, and psychological development. Of course, as at present, the donor must be relieved of all responsibility, both legal and financial. PMID- 8348164 TI - A comparative study of human chorionic gonadotropin, placebo, and bed rest for women with early threatened abortion. AB - OBJECTIVE: To compare the effect of hCG therapy with placebo or bed rest in women with threatened abortion. DESIGN: Random assignment, double-blind. SETTING: Community hospitals. PATIENTS AND INTERVENTIONS: Sixty-one women with viable pregnancies under 8 weeks' gestation on admission to hospital were randomly allocated to receive injections of hCG or placebo, or were advised to rest in bed. MAIN OUTCOME MEASURES: Abortion vs. continuation of pregnancy at 16 weeks' gestation. RESULTS: Thirty-one aborted: 6/20 on hCG, 10/21 on placebo, 15/20 on bed rest. hCG vs. bed rest, P < .01; placebo vs. bed rest, hCG vs. placebo--not significant. Plasma progesterone: continuing pregnancy > abortion, P < .01; continued with hCG vs. aborted on placebo, P < .001; continued with hCG vs. aborted with bed rest, P < .001. No significant differences in pregnancy/birth complications or infants' birth weight. Female/male ratio was 2:1. CONCLUSIONS: hCG is significantly better than bed rest. PMID- 8348163 TI - Ovulation induction with low doses of "pure" follicle stimulating hormone using a fixed protocol in patients with polycystic ovarian disease. AB - OBJECTIVE: Use of a low, fixed dose of purified FSH to induce ovulation in polycystic ovarian syndrome. DESIGN: Fixed protocol, using 75 IU/day of "pure" FSH starting on day 1-5 of menses. SETTING: University outpatient clinic. PATIENTS AND INTERVENTIONS: Seventeen patients, aged 18-38, with clomiphene resistant polycystic ovarian syndrome, for 23 cycles. All received 50 mg medroxyprogesterone to induce menstrual flow. "Pure" FSH given i.m. for eight to ten days. If follicle reached > or = 18 mm, hCG (5,000 IU) was given, in one-half of cases, in a single dose to induce rupture. MAIN OUTCOME MEASURES: Hormonal measurements (plasma LH, FSH, estradiol, testosterone, progesterone); daily, LH/FSH ratio; daily abdominal sonogram. RESULTS: I: No follicular growth (3 cycles; 13%); II: Inadequate follicular growth (< or = 14 mm--6 cycles; 26%); IIIa: Follicle > or = 18 mm, hCG given; 100% ovulatory; IIIb: Follicle > or = 18 mm, no hCG given; 2/7 ovulatory. Hyperstimulation: one (moderate) in IIIa; one (mild) in IIIb. CONCLUSIONS: Fixed protocol of low-dose, "pure" FSH produces good results, especially combined with hCG, which is effective up to 48 hours after last injection of FSH. PMID- 8348165 TI - Percentages of acrosome-reacted sperm in human semen close to liquefaction and following acrosome-reaction inducing treatment. AB - OBJECTIVES: To compare spermatozoa from normal and subnormal seminal specimens in their ability to undergo the acrosome reaction, as defined by the triple-staining method. METHODS: Normal (39) and abnormal (23) specimens were examined by staining promptly after liquefaction. In a total of 32 specimens, the reaction was examined before and after acrosome-reaction-inducing treatment, which was essentially incubation of isolated sperm in BWW containing 0.3% BSA and 4 mM calcium chloride. RESULTS: Percentage of vital acrosome-reacted sperm (true acrosome reaction) of untreated specimens: normal, 10.0 +/- 4.9%, abnormal, 5.3 +/- 3.6% (P < .001). After treatment: increase in reacted sperm from normal specimens, 9.0 +/- 7.1% to 22.7 +/- 14.0% (P = .005); abnormal specimens, 5.4 +/- 2.9% to 7.3 +/- 4.2% (NS). CONCLUSIONS: Low capability of sperm to undergo the acrosome reaction might be a decisive factor in the low fertility potential characterizing the majority of abnormal semen. Effort in infertility treatment should be directed to increasing the proportion of acrosome-reacted sperm. PMID- 8348167 TI - The umbilical cord: a study of 1,000 consecutive deliveries. AB - OBJECTIVE: To establish base-line data on cord length among Igbo parturients of Eastern Nigeria, especially relationship between age and parity, gestation length, sex and weight of newborn, placental weight. DESIGN: Retrospective analysis of 1,000 consecutive deliveries. SETTING: Mission hospital. MATERIALS AND METHODS: Placental length of umbilical cord, placental weight, and prenatal data. RESULTS: Cord length varied between 15 cm and 130 cm (mean, 51.5 cm). No relationship found to parity, maternal age, or sex of baby. Increase in cord length with birthweight and gestational age, up to term. Correlation between umbilical length and placental weight, with a variation according to lie of the fetus: longest in cord encirclement and unstable lie, shortest in breech presentation, transverse lie, and twin birth. PMID- 8348166 TI - A simple and efficacious criterion based on serum LH levels to time hCG administration for human in vitro fertilization. AB - OBJECTIVE: To test the efficacy of a simple criterion--LH level--for administration of hCG in an IVF program. DESIGN: Prospective, with retrospective analysis of other criteria for hCG administration. SETTING: University hospital IVF program. PATIENTS AND INTERVENTIONS: Eighty-four patients, in 110 cycles, were given 150-300 IU at 10-11 A.M. daily beginning on day 3 of the cycle. Serum LH measured daily 8:30-9:30 A.M., hCG administered on night of day LH level first exceeded J, defined as minimum value + (day 3 value-minimum) x 1/3. OUTCOME MEASURES: Pregnancy (after IVF + ET); serum concentrations of estradiol and LH. RESULTS: Total and ongoing pregnancy per cycle: 35% and 27% respectively. If hCG is administered one day early or late by the J criterion, the pregnancy rate is reduced. CONCLUSIONS: Pregnancies occurred over wide follicle diameter (14-21 mm) and estradiol level (229-2,050 pg/mL) ranges. LH is recommended for timing hCG administration. PMID- 8348168 TI - The importance of pre-freeze equilibration of glycerol in cryopreservation of human spermatozoa and the biochemical conversion of glycerol. AB - OBJECTIVE: To find optimal conditions for cryopreservation of human spermatozoa with glycerol as cryoprotectant. MATERIALS AND METHODS: Pooled semen from groups of three normal donors was allowed to liquefy for 30 minutes at 37 degrees C. Samples were subjected to a prefreeze equilibration interval of 0, 30, or 60 minutes, with 5% or 10% glycerol, at 0 degrees C, 22 degrees C, or 37 degrees C. Samples were frozen in liquid nitrogen for 24 hours, thawed, and assessed for post-thaw motility. Uptake and metabolism of glycerol were studied using [3H] glycerol. Thin-layer chromatography of ethanol extracts of washed spermatozoa that had been incubated with the labeled glycerol was used to determine metabolic products. RESULTS: Overall best cryopreservation was obtained at 37 degrees C with 5% glycerol and 30 minutes' prefreeze incubation. Labeled glycerol was incorporated into both polar and nonpolar metabolites. Two chromatographic peaks were found associated with the spermatozoa, and one peak was found in the incubation medium. PMID- 8348170 TI - Consumers will have the last word on reform. PMID- 8348169 TI - An approach to pathogenesis of male infertility with anti-sperm antibodies. AB - OBJECTIVE: To determine subsets and functional characteristics of peripheral blood lymphocytes in men with infertility associated with anti-sperm antibodies. SUBJECTS AND METHODS: Blood from 28 infertile men with anti-sperm antibodies and 34 fertile control males were tested for the lymphocyte subsets by indirect immunofluorescence and also for lymphocyte transformation responses to phytohemagglutinin (PHA), ConA, and pokeweed mitogen (PWM). Also studied were effects of seminal plasma on the lymphocyte transformation responses. RESULTS: Percentages of CD3, -4, and -8 cells and lymphocyte blastogenic responses to PHA and ConA were significantly lowered in patients. Percentage of B-cells, CD4/CD8 ratio, and blastogenic response to PWM were increased. All seminal plasmas suppressed lymphocyte blastogenesis induced by PHA, PWM, and ConA, but the suppressive effect on PHA and PWM by patients' plasma was less than that of controls. CONCLUSIONS: The results suggest that number and function of T lymphocytes, especially CD8 cells, are lessened and those of CD4 and B-cells enhanced in the infertile patients. These factors would be conducive to development of an immunologic response to sperm. PMID- 8348171 TI - Close to home. Interview by Terese Hudson. AB - The hospital is an integral part of the community, according to James May, CEO and president of Legacy Portland (OR) Hospitals. May has put this principle to work concretely by loaning employees money for initial costs on homes near Emanuel Hospital and Health Center in northeast Portland. Now in its second year, the program has already helped 25 employees purchase homes in a 19-square-mile area targeted for redevelopment. Loans of up to $5,000 for homes with a purchase price of $65,000 or lower are available. The loans can be used for down payments, pre-paid reserves or closing costs. Legacy forgives 20 percent of a loan's outstanding balance each year to employees in good standing. This encourages employees to stay for at least five years. Only the interest payments on the outstanding balance are paid back to Legacy. May spoke recently with Senior Editor Terese Hudson about the program's genesis. PMID- 8348172 TI - Prepared for uncertainty? AB - National health care reform legislation will affect hospitals in ways as dissimilar as hospitals themselves. How prepared are they? Hospitals & Health Networks, in conjunction with Premier Hospitals Alliance, Westchester, IL, surveyed 402 CEOs and chief operating officers to gauge their responses to anticipated changes and garner their opinions on how reform will affect their hospitals. PMID- 8348173 TI - Next steps for nursing. PMID- 8348174 TI - Breaking down barriers. Cambridge Hospital ensures access to care for diverse community groups. AB - The American Hospital Association and the Baxter Foundation present the Foster G. McGaw Prize annually to a hospital that distinguishes itself in meeting the diverse health and social needs of its community. The winner receives $75,000; the three finalists each receive $10,000. This year's winner and finalists were chosen from more than 100 entries. Applicants were judged by a panel of 77 hospital executives and a nine-member prize committee of health care experts. PMID- 8348175 TI - Constructive change. Strong strategic plans can help hospitals keep facility plans in line. PMID- 8348176 TI - Wake-up call. Many physicians don't become aware of managed care until it rolls into their neighborhood. AB - Though not yet embracing managed care with open arms, more physicians are realizing that it's a reality that they can't ignore. As a result, organizations both new and old are providing information on managed care for physicians. PMID- 8348177 TI - Linking their futures. Hospitals and physicians meet challenges posed by PHOs. AB - Attorneys and executives who have built PHOs say they aren't essential for risk contracting and integrated delivery systems, but are extremely helpful. But they add that skilled, careful planning is key to the ultimate success of any PHO. PMID- 8348178 TI - Albuquerque, New Mexico. Systems integration is prelude to development of AHPs (accountable health plans) PMID- 8348179 TI - Getting the message out. The AHA gears up to respond to the White House reform plan. PMID- 8348180 TI - Soviet crisis: a matter of perspective. PMID- 8348181 TI - Why so many women? Part 1. Systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that predominantly affects women. While numerous factors may account for the etiology of SLE, the influence of gender-based sex hormones on the prevalence of SLE and autoimmune disorders among women is currently being evaluated. PMID- 8348182 TI - Managing the patient with liver failure. AB - Liver failure affects virtually all aspects of body functioning, which challenges medical-surgical nurses to deliver effective comprehensive care. Managing patients with liver failure requires a thorough understanding of hepatic physiology and the pathophysiology of liver disease failure. PMID- 8348183 TI - Coping and emotion in women undergoing cardiac surgery: a preliminary study. AB - There is limited knowledge about how women manage the experience of cardiac surgery. This pilot study examined how women coped with surgery and their emotions in the perioperative period. There was no change in coping or emotion from the day before surgery to the fifth postoperative day, and coping was unrelated to emotion. Preoperative and postoperative confusion and distress were positively correlated. While preliminary, these results raise implications for medical-surgical nursing practice and research. PMID- 8348184 TI - Beating a path to nursing's door: scientific support for holistic practice. AB - Nursing has a long history of a holistic focus on patient care. The current emphasis on the need for holism indicates that the "world" is more aware of the value of nursing. To enhance this possibility, nurses need to use empirical evidence to support holistic practice. PMID- 8348185 TI - Post-anesthesia assessment: what medical-surgical nurses need to know. AB - Post-anesthesia patient assessment helps predict the acuity and nursing care needs of patients upon discharge to critical, general, or home care. The goals of postanesthesia assessment, with a focus on the potential respiratory, cardiovascular, neurologic, and other complications are discussed. PMID- 8348186 TI - Mourning: a concern for medical-surgical nurses. AB - Medical-surgical nurses working in a variety of settings with dying patients and their families play an important role in facilitating grieving. They can do much to help dying patients have a more peaceful death by listening to them. They can facilitate healing among families prior to death. They can help surviving family members begin a more healthy pattern of mourning. The tasks of mourning offer a useful guide for responding to the needs of the bereaved from a variety of cultural perspectives. Nurses can gain a greater sense of satisfaction in working with dying patients and grieving survivors by incorporating this framework into their practice. PMID- 8348187 TI - Surviving NCLEX-RN reexamination. PMID- 8348188 TI - Developing a nursing information systems department. Part I: Stating the vision. PMID- 8348189 TI - Independent contractor or employee? PMID- 8348190 TI - Understanding corticosteroids: pharmacologic and adverse effects. PMID- 8348192 TI - A comparison of ethical resources. PMID- 8348191 TI - Understanding corticosteroids. Estrogens' potential role in autoimmune diseases. PMID- 8348193 TI - Overcoming barriers to research utilization with researched-based practice guidelines. PMID- 8348195 TI - Tricyclic antidepressants versus electroconvulsive therapy: a review of the evidence for efficacy in depression. AB - The author examines the thesis that electroconvulsive therapy is superior to tricyclic antidepressants in treating nonpsychotic major depression. Every study published in English since 1960 comparing electroconvulsive therapy against tricyclics in treating this condition was reviewed. Because of numerous methodological weaknesses in the studies, the data is inadequate to support the claim that one treatment is superior to the other. PMID- 8348194 TI - Are controls in schizophrenia research "normal"? AB - The psychiatric assessment by structured interview and family history of mental disorder in normal volunteers recruited by advertisement for a study of brain structure and function in psychosis is described. Nine of 51 volunteers (17.6%) who passed a phone screen were excluded after a structured interview for major psychopathology. Of 35 completers, 10 (28.6%) had subthreshold mood or substance use but were included in the study. Only 16 subjects (45%) had a negative family history by FH-RDC. Diagnoses in family members included substance abuse (31%), mood disorder (11%), psychosis (9%), and other/undiagnosed (14%). Ventricular enlargement was evaluated by magnetic resonance imaging in two planes. Ventricular size was bimodally distributed in the males, and the group with larger ventricles was more educated and had higher scores on the 8 (Schizophrenia) scale of the MMPI (F = 5.44, p = .0099). Our results suggest that 'normal' volunteers for psychiatric research have personal or family psychopathology which motivates them to participate. As the sensitivity of biological instrumentation increases, the characteristics of the control group must be anticipated in the design and recruitment. PMID- 8348196 TI - Clinical correlates of valproate augmentation in refractory bipolar disorder. AB - We examined the clinical correlates of valproate (VPA) therapy in refractory bipolar disorder. Retrospective chart review was used to collect demographic and clinical data including present diagnosis, diagnosis at illness onset, duration of illness, number of hospitalizations, VPA dose, side effects, and maximum serum concentration. Global response was rated once patients serum VPA exceeded 50 mg/dL. The charts of all inpatients admitted over a two-year period and treated with VPA for acute episodes of bipolar disorder in manic, mixed, or depressed phase were reviewed. Seventeen of these patients began VPA augmentation while hospitalized and became the cohort for review. Patients were excluded if VPA was started prior to admission or the patient was discharged less than one week after drug initiation. Patients were not excluded on the basis of EEG, CT, or neurological exam findings. Overall, 12 of 17 (71%) of the patients showed a moderate or marked improvement while 5 of 17 (29%) showed mild or no response. Responders were older and had a longer duration of illness with an increased number of hospitalizations. There was a strong trend for responders to achieve a higher serum VPA level. A significant positive correlation was found between response in acute mania and psychotic symptoms at first episode of illness. PMID- 8348197 TI - Barbiturate anticonvulsants in refractory affective disorders. AB - Despite an increasing literature demonstrating both acute and long-term positive psychopharmacological effects of both valproate and carbamazepine, phenytoin has remained a controversial intervention, and barbiturate anticonvulsants have generally received poor press with regard to psychotropic effects. In the present investigation, 27 seizure-free, affectively ill patients who received therapeutic trials of primidone and/or mephobarbital after failing on antidepressants, lithium, carbamazepine, valproate, and phenytoin were analyzed with regard to effects on illness severity and affective cycle rate over a period of as long as four years. Nine (33%) of the patients had a sustained positive therapeutic effect on affective state and/or psychotic symptoms to primidone and three (11%) had positive effects on mephobarbital after primidone failure. Four (15%) had brief positive effects that were not sustained, and the remaining 11 (41%) had no effects or negative effects to these agents. The theoretical and practical implications of this new and unexpected finding are discussed. PMID- 8348198 TI - Clinical correlates of self-mutilation among psychiatric inpatients. AB - The charts of 660 consecutive admissions to a university psychiatric hospital were examined. After excluding those with mental retardation, 32 patients who had mutilated themselves and 88 patients admitted for unsuccessful suicide attempts were identified. Women were significantly overrepresented among the mutilators, but the groups did not differ with respect to age. Most analyses were restricted to women, of whom 27 were self-mutilators and 51 were nonmutilating suicide attempters. Mutilators were less likely to receive diagnoses of major depression or adjustment disorder but were more likely to have a history of substance abuse and receive Axis II diagnoses. The mutilative behavior was generally repetitive. The most common form was superficial cutting of the arms and wrists. Reports of lifetime sexual or physical abuse were more common among mutilators. Mutilators also had frequent histories of suicide attempts distinct from their mutilation behavior, multiple hospitalizations, and transfer to state hospitals for longer term care. These findings suggest a chronic course with significant morbidity and associated features which may be of clinical significance. PMID- 8348200 TI - An open trial of methyltetrahydrofolate in elderly depressed patients. AB - 5-methyltetrahydrofolate (MTHF) is a naturally occurring substance involved in the synthesis of s-adenosyl-l-methionine (SAMe), a major source of methyl groups in the brain. To assess the efficacy of a gastro-resistant, oral preparation of MTHF, 20 elderly patients with a DSM-III-R diagnosis of depressive disorder and a HAM-D-21 score > or = 18 underwent 6-weeks of open-label treatment with 50 mg per day of oral MTHF. Of these 20 patients, 16 completed at least 4 weeks of treatment and showed a markedly significant improvement in their depressive symptoms at endpoint, with 81% of them being considered responders. There were no clinically relevant changes in the routine laboratory tests during the study, and no adverse events considered to be definitely drug-related were reported. PMID- 8348199 TI - Antidepressant side effects and physician prescribing patterns. AB - We studied the following questions: (1) Do physicians preferentially prescribe antidepressants (ADs) with the least side effects (SEs) of sedation, orthostatic hypotension, and anticholinergic activity; (2) Have there been any recent changes in prescribing patterns; and (3) Do patterns differ for psychiatrists and nonpsychiatrists. Data on psychiatrist and non-psychiatrist outpatient prescribing of specific ADs were obtained from the National Prescription Audit (NPA) for 1986 and 1989. In 1986, physicians did not minimize the use of ADs with the most of these SEs. The 1989 data indicate that psychiatrists made a major change toward prescribing more low SE ADs and less ADs with the most SEs. The data for nonpsychiatrists also suggest some movement in this direction. The availability of fluoxetine and the concomitant focus on SEs may have contributed to this shift. Further investigation is needed to clarify factors that influence physicians' choices of ADs. PMID- 8348201 TI - Presence of psychiatric morbidity in prison population in Kuwait. AB - This paper surveys the prevalence of psychiatric morbidity in a Kuwaiti prison. The rate of major psychosis was considerably lower than the rate reported in other prison studies. Twenty-five percent of the sample had generalized anxiety disorder of a reactive nature which was most probably related to imprisonment itself. There was a preponderance of individuals suffering from personality disorder, alcoholism, and drug abuse problems. Prisoners with a diagnosis of major psychosis had very little exposure to psychiatrists and the large number of recidivists reflects the lack of a probation service. Financial embezzlement and drug/liquor smuggling remain the crimes of choice in Kuwait. Some underlying sociocultural factors are discussed and the need for an alternative prison-based therapeutic community service is emphasized. PMID- 8348202 TI - Relationships between thyroid indices and symptoms of anxiety in depressed outpatients. AB - Scores on rating scales measuring symptoms of depression, panic anxiety, state anxiety, trait anxiety, and agoraphobic avoidance were correlated, using multivariate statistics, with total thyroxine- and thyrotropin-releasing hormone concentrations in outpatients with major depression. A significant inverse relationship was demonstrated between agoraphobic avoidance and total thyroxine concentrations in female patients. No other symptom ratings were significantly associated with these thyroid indices. The depressed patients scored in the clinically significant range for agoraphobic symptoms. Assessment of agoraphobic avoidance may help identify a clinically and biologically distinct subgroup of depressed patients. PMID- 8348203 TI - Identification of treatment-resistant depressives who respond favorably to carbamazepine. AB - Thirteen depressed patients with documented histories of failure to respond to tricyclic antidepressant medications who reported multiple partial seizure like symptoms were given open trials of carbamazepine. Eleven of the 13 showed moderate to substantial improvement in affective status that was accompanied by significant mean changes on the Beck or Hamilton depression scales. In addition, the mean number of reported partial seizure-like symptoms decreased significantly with treatment. Dichotic word listening performance was the only neuropsychological variable that was impaired at baseline and was also the only cognitive performance that improved following treatment. These preliminary observations suggest that there is likely to be a subgroup of treatment resistant, carbamazepine-responsive depressives who can be identified by evaluating for the presence of multiple partial seizure-like symptoms. PMID- 8348204 TI - Phenobarbital versus clonazepam for sedative-hypnotic taper in chronic pain patients. A pilot study. AB - A randomized, double-blind controlled trial is reported comparing phenobarbital and clonazepam for the purpose of sedative-hypnotic taper in inpatients with chronic, nonmalignant pain. After receiving the Minnesota Multiphasic Personality Inventory (MMPI) and a standardized psychiatric diagnostic interview, patients' baseline sedative-hypnotic use was assessed over 48 hours. Baseline use was converted into phenobarbital or clonazepam equivalents and administered in four doses daily using a blinded liquid pain cocktail. Baseline dose was maintained for two days and then tapered by 10% per day. Over the first week of taper, differences in mean and maximum Beck Anxiety and Benzodiazepine Withdrawal scores were not significant. However, when scales 1, 3, or 8 of the MMPI were taken as covariates, differences on the Withdrawal Scale only increased to a trend level for mean scores and to a significant level for maximum scores. These findings support the superiority of benzodiazepines over barbiturates for sedative hypnotic taper for symptoms of withdrawal but not of recurrent or rebound anxiety. PMID- 8348205 TI - Multiple personality disorder and borderline personality disorder. Distinct entities or variations on a common theme? AB - We report data from a comparison of 14 subjects with multiple personality disorder (MPD) and 13 subjects with borderline personality disorder (BPD). There were few significant differences between the groups. The authors discuss the concept of MPD as an epiphenomenon of BPD, and argue their fundamental similarity. PMID- 8348206 TI - A calendar savant with autism and Tourette syndrome. Response to treatment and thoughts on the interrelationships of these conditions. AB - A case of a calendar savant with infantile autism and Tourette syndrome is presented. Pharmacotherapy and comorbidity issues are discussed in terms of the interrelationships of these conditions and obsessive-compulsive disorder. PMID- 8348207 TI - Rational polypharmacy in schizophrenia. AB - Approximately 10 to 30% of patients with schizophrenia show poor response to neuroleptics alone. An initial evaluative and treatment approach to these patients is outlined, and the literature on adjunctive treatments, which seek to augment neuroleptic effects, is reviewed. The greatest evidence for efficacy has been shown for lithium, benzodiazepines, carbamazepine, reserpine, and electroconvulsive therapy, although individual patients may also respond to propranolol, clonidine, valproic acid, and L-dopa. Antidepressants may also be useful for treating comorbid depression in nonacutely psychotic patients. One general theme is that no one adjunctive treatment benefits all patients; indeed, only a minority of patients responds to any given agent. Therefore, the choice of specific treatments is best guided by the clinical characteristics of the individual patient. These observations raise the possibility that subgroups of schizophrenia exist; delineation of differences in clinical response to biochemically distinct agents may help elucidate such underlying differences between patient groups. PMID- 8348209 TI - Effect of streptozotocin-induced diabetes on electrically evoked erection in the rat. AB - This study was designed to investigate whether experimental diabetes in rats could functionally affect reflexogenic erection. Erection was elicited by means of electrical stimulation of the dorsal nerves of the penis and recorded as intracorporeal pressure. Rats were examined 1, 3 and 6 months after diabetes induction by streptozotocin. Three and 6 month diabetes caused a significant decrease of latency for erection and a slower phase of detumescence when compared to age-matched controls. In addition, a trend for a lower developed intracorporeal pressure was present in the 6 month diabetes group. Our results indicate that experimental diabetes is associated with alterations of reflexogenic erection. PMID- 8348208 TI - Pelvi-perineal rehabilitation for dysfunctioning erections. A clinical and anatomo-physiologic study. AB - We have studied penile structure in 24 cadaver specimens and 155 patients have been treated for organic impotence by physiotherapy. Special attention has been focused on the closure mechanism of the corpora cavernosa during erection. We have found that the leakage factor of the corpora cavernosa is, among other things, influenced by the ischiocavernous muscles. Based on the above, we propose a model for the anatomic and physiologic basis of interference of the ischiocavernous muscles in venous occlusion during penile erection. Moreover we suggest that patients with erectile dysfunction should undergo pelvi-perineal rehabilitation in order to strengthen and control ischiocavernous muscles. PMID- 8348210 TI - Intracavernosal kinetics of eicosanoids and endothelin during erection. Data from human and animal studies on intrapenile and systemic prostaglandins. AB - The release of mediator substances of the arachidonic acid cascade is closely related to the functional state of the endothelium. A significant lower prostacyclin/thromboxane A2 ratio in penile plasma of organogenic impotent patients in comparison to patients with psychogenic erectile dysfunction has been described in the literature. We observed the time-related liberation of prostacyclin, thromboxane A2 and the vasoactive peptide endothelin for 16 minutes of a drug-induced erection. We compared kinetics of patients with penile deviation and transsexualism, to patients suffering from severe organogenic impotence. We assessed the usefulness of the prostacyclin-to-thromboxane A2 ratio as a possible indicator of corporal degeneration. An animal model has been created to observe differences between rabbits under 100 days of standard diet alimentation, rabbits under cholesterol enriched diet and rabbits with hereditary hyperlipidemia type II A. Hyperlipidemia is suspected to be one possible factor causing organogenic impotence. Enzyme-immuno-assays were used for the determination of all substances. The systemic prostacyclin-to-thromboxane A2 ratio differed significantly between control rabbits and rabbits with hyperlipidemia. Prostacyclin, thromboxane A2 and endothelin in corpus cavernosum plasma showed a typical profile during spontaneous and drug-induced erection. A significant difference between groups of patients suffering from organogenic or psychogenic impotence could not be found. The value of the determination of the studied substances in differential diagnosis seems to be dubious. PMID- 8348211 TI - Pudendal versus limb nerve electrophysiological abnormalities in diabetics with erectile dysfunction. AB - It is of some interest to diagnose polyneuropathy and/or sacral neuropathy in diabetic males with erectile dysfunction. Non-invasive electrophysiological measurements with surface electrodes, which are widely available, have been applied to determine the diagnostic yield of several electrophysiologic parameters for assessing polyneuropathy including the pudendal nerve in impotent diabetics. Latencies of the bulbocavernosus reflex and the pudendal somatosensory evoked potentials were measured in a group of 28 diabetic patients with an erectile dysfunction as their main complaint, as well as in a group of 20 potent males without systemic disease. In diabetic patients motor conduction measurements of one median and peroneal nerve and sensory conduction measurements of one median and sural nerve were also performed. In 15 patients abnormalities of the peripheral nerve conduction were demonstrated whereas abnormalities of the bulbocavernosus reflex and/or cortical somatosensory evoked potentials were demonstrated in eight. Five patients had both types of abnormalities. In the patient group no differences could be demonstrated between those with Type 1 or Type 2 diabetes. The only significant clinical/neurophysiological correlation was found between the absence of the bulbocavernosus reflex on clinical examination and its prolonged latencies on electrophysiological measurement. The study showed that a bigger yield of abnormal results was obtained when pudendal nerve function parameters were included in the evaluation of diabetics with erectile dysfunction. Considered separately, however, the battery of electrophysiological tests evaluating limb nerve function seems more sensitive in diagnosing neuropathy than electrophysiological assessment of pudendal nerve function alone. PMID- 8348213 TI - The success of microsurgical penile revascularization in treating arteriogenic impotence. AB - The treatment of arteriogenic erectile dysfunction with revascularization techniques has been controversial both in terms of its use and the type of surgical repair. Success rates reported in the literature are based almost exclusively on patient testimonial, without the use of objective post-operative criteria. At our institution from 7/88 through 8/91, 18 patients were treated for arteriogenic impotence using microsurgical penile revascularization. The patient population ranged in age from 23 to 64 years, and each patient underwent a complete history and physical examination, serum hormone testing, psychological evaluation of patient and partner, biothesiometry, penile plethysmography, nocturnal penile tumescence/rigidity testing with a Rigiscan device, and selective pudendal arteriography. One patient was status post a pelvic fracture, 2 lacked identifiable risk factors, 2 had diabetes, 6 were heavy smokers, and 7 had hypertension. Pre-operatively each patient had a suspicious medical history, abnormal plethysmography, abnormal Rigiscan testing, and a hemodynamically significant lesion on angiography. Revascularization was done by anastomosing the inferior epigastric artery to the deep dorsal veing and dorsal artery, or the deep dorsal vein alone if both arteries were atretic. Postoperatively, all 18 patients underwent a personal interview, repeat penile plethysmography, and repeat Rigiscan testing. Six patients reports successful coitus and an additional four were having coitus with the aid of intracavernous pharmacotherapy. Seventy eight percent (14/18) had improved tracings on penile plethysmography, and 56% (10/18) had normal erectile capability by Rigiscan testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348212 TI - Prostaglandin E1 diluted solution: preparation technique and stability evaluation. AB - The authors describe their prostaglandin E1 dilution method for the treatment of male erectile dysfunction. Preparation stability was investigated. Results suggest that PGE1 diluted solution can last as long as 90 days, while decreased concentrations of PGE1 are detected after three months. PMID- 8348214 TI - Current trends in corpus cavernosum EMG. Conclusions of the 'First International Workshop on Smooth Muscle EMG Recordings/Leiomyogram' April 15 to 17, 1993 in Mannheim, Germany. PMID- 8348215 TI - Criteria for examiner-independent nocturnal penile tumescence and rigidity monitoring (NPTR): correlations to invasive diagnostic methods. AB - 78 patients (pts.) with erectile dysfunction (ED) underwent conventional diagnostic evaluation including NPTR monitoring with the Rigiscan, intracavernous drug testing, dynamic cavernosometry, doppler evaluation, pharmaco-angiography and neurologic tests. Only erections of the best rigidity recorded over three nights served for classification into three classes of rigidity. Patients with neurogenic impotence showed significantly poorer and fewer erectile events per hour than vasculogenic impotent men. Patients with arteriogenic ED had better erections than patients with venogenic or mixed arterio-venogenic ED. Severity of organic ED during conventional diagnostic work-up correlated to loss of rigidity during NPTR recordings, but no differential diagnosis between arteriogenic, venogenic or neurogenic impotence could be made with NPTR data alone. The presented criteria for NPTR evaluation permit a time-saving, examiner-independent analysis. PMID- 8348216 TI - The performance of the Rigiscan in the measurement of penile tumescence and rigidity. AB - The validity of the Rigiscan as a measure of both penile circumference and rigidity was assessed. In the first study, the Rigiscan was used simultaneously with a mercury-in-rubber strain gauge to monitor nocturnal penile tumescence. The Rigiscan was found to underestimate the circumference proportional to the degree of erection. In a second study a calibration system was developed which allowed independent variation of circumference and rigidity. Assessment of the Rigiscan with this system confirmed that circumference was underestimated, particularly at lower levels of rigidity, and also that different devices consistently recorded different degrees of rigidity. The use of this type of system for regular calibration is recommended, and other potential improvements in the device for research purposes are discussed. PMID- 8348217 TI - Erectile dysfunction in men under 40: etiology and treatment choice. AB - We undertook a retrospective review of 100 impotent men under age 40 to determine the underlying etiologic factors in the group and to evaluate the role of surgery in their care. Although patients ranged in age from 18 to 40 (mean--32.2 years), the number of patients increased steadily with advancing years. The majority of patients (72) had vasculogenic impotence (arteriogenic--15, venogenic--46, mixed- 11), followed by psychogenic (13), neurogenic (12) and other causes (4). The differential diagnosis did not correlate with age. Contributing factors were present in 76%, trauma and substance abuse being most common. Essentially equal numbers of patients were treated surgically (40) and with intracavernous injection of vasoactive agents (39). Considerably fewer had a vacuum constriction device (5), oral medication (5), psychotherapy (4), other therapy (4), and none (3). The majority of patients referred to our tertiary urologic practice for treatment of vasculogenic impotence were sent by other urologists. Although the referral source did not appear to influence the choice of treatment, it probably has accounted for the preponderance of vasculogenic impotence in this series. PMID- 8348218 TI - Hypoglycemia in the neonate. AB - After a brief history of the development of neonatal hypoglycemia, this review emphasizes the current approach to the anticipation, diagnosis, and management of the neonate with a low plasma glucose concentration. Both transient and recurrent or persistent hypoglycemia are discussed. Current techniques for studying the neurophysiologic and endocrine-metabolic effects of significant hypoglycemia provide new approaches for establishing relevant definitions of significant hypoglycemia, its prognosis, and pathogenesis. The inadequacy of glucose oxidase strips for screening, the definition of high risk infants, new definitions for low plasma glucose concentrations and their treatment are discussed. New data concerning the hereditary aspects of hyperinsulinemia, the role of glucose transporters, and the ability of the neonate to respond to significantly low glucose values are presented as well. PMID- 8348219 TI - The evaluation of 24-hour spontaneous GH secretion in short children: relationship between mean concentration and pulsatile parameters. AB - In 116 short children (height < -1.6 SDs), the authors examined GH secretion over 24 hours, by taking blood samples every 20 min and performing an electroencephalographic sleep control. The following GH parameters were evaluated: 24-h mean GH concentration (MGHC); maximum GH peak during the initial cycle of sleep (iMGHP), the nocturnal 12 h (nMGHP) or diurnal 12 h (dMGHP), the number of GH pulses over 24 h (NP), or nocturnal 12 h (nNP) or diurnal 12 h (dNP), the mean pulse amplitude over 24 h (MPA), or nocturnal 12 h (nMPA) or diurnal 12 h (dMPA). The subjects were divided into 3 groups: group 1, 12 subjects with low responses to provocative tests and MGHC < 3 ng/ml; group 2, 36 subjects with normal responses to provocative tests and MGHC < 3 ng/ml; group 3, 68 subjects with MGHC > 3 ng/ml. MGHC was highly correlated (p < 0.001) with iMGHP (r = 0.80), nMGHP (r = 0.82), dMGHP (r = 0.59), MPA (r = 0.85), nMPA (r = 0.86), dMPA (r = 0.56), NP (r = 0.70), nNP (r = 0.68), dNP (r = 0.46). By the analysis of the regression equations, the values corresponding to 3 ng/ml for MGHC were 11.08 ng/ml for iMGHP, 11.66 ng/ml for nMGHP, 5.21 ng/ml for dMGHP, 7.29 ng/ml for MPA, 8.40 ng/ml for nMPA, 4.25 ng/ml for dMPA, 3.2 for NP, 2.41 for nNP and 0.78 for dNP. By using these values as cut-off points, the diagnostic accuracy yielded 83.6% for iMGHP, 84.5% for nMGHP, 69.8% for dMGHP, 92.2% for MPA, 90.5% for nMPA, 81.9% for dMPA, 80.2% for NP, 77.6% for nNP, 71.5% for dNP. In conclusion, we found a strong correlation between mean GH secretion over 24 h and the number or amplitude of pulses: particularly, nocturnal pulsatile GH parameters show a higher correlation in comparison with diurnal pulsatile GH parameters, so that the examination of GH values during nocturnal hours may be considered a reliable index of GH secretory status. PMID- 8348220 TI - Final heights in 45,X Turner's syndrome with spontaneous sexual development. Review of European and American reports. AB - STUDY OBJECTIVE: To assess the effect of endogenous estrogen secretion on the final heights of patients with 45,X Turner's syndrome. DESIGN: European and American reports of patients with 45,X Turner's syndrome and spontaneous sexual maturation in which final heights were available were analyzed and compared with existing norms for untreated patients with Turner's syndrome. Subgroups of patients were compared as a means of distinguishing low from normal endogenous estrogen exposure, and the effect of the age of menarche was assessed. PATIENTS: Twenty-three cases were collected, including eight who became pregnant. One had full somatic maturation but did not menstruate. RESULTS OF ANALYSES: Mean height of all 23 patients was 140.8 cm +/- 8.07 (s.d.) vs 143.1 cm +/- 6.0 (p = 0.035) for literature norms for Turner's syndrome. Mean height of those who achieved pregnancy was 138.6 cm +/- 8.21 (p = 0.035 vs literature norm); of those with normal gonadotropins 137.5 cm +/- 6.03; and of those with high gonadotropins 139.2 cm +/- 1.44 (p = 0.374). Age of menarche was available in 21 and showed no correlation with final height. CONCLUSIONS: Physiological and subphysiological endogenous secretion of estrogen in Turner's syndrome does not increase final height, suggesting that even low-dose exogenous estrogen would not increase ultimate stature in these patients. PMID- 8348221 TI - Auxological and biochemical parameters in assessing treatment of infants and toddlers with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. AB - We studied height velocity (HV), bone age progression (delta BA/delta CA), urinary pregnanetriol (PT) and plasma 17-hydroxyprogesterone (17-OH-P) during the first years of life in 12 patients with 21-hydroxylase deficiency, treated by cortisone acetate. In the well-controlled phases normal growth rate (SDS between 1 and +1), satisfactory bone age progression (delta BA/delta CA < or = 1) and no clinical sign of poor treatment were found; in the undertreatment phases enhanced growth rate, rapid bone age progression and, in some instances, signs of virilization were found; in the overtreatment phases, reduced growth rate was the only sign of poor treatment. Hormonal values were only weakly correlated to therapeutic control. Therefore, growth rate evaluation can represent the best method of monitoring treatment in very young patients with 21-hydroxylase deficiency. PMID- 8348222 TI - Growth hormone and insulin-like growth factor I plasma levels in patients with hypophosphatemic rickets. AB - The cause of the growth retardation present in patients with hypophosphatemic rickets has not been totally elucidated. There has been a previous report of a growth hormone deficit in a group of these patients. To verify this abnormality we studied two groups of patients with hypophosphatemic rickets, one with (n = 6) and the other without (n = 7) treatment with calcitriol and oral phosphates. All patients in both groups showed a normal growth hormone response (> 10 micrograms/l) to standard stimulatory tests and normal IGF-I plasma levels. Mean IGF-I plasma levels were not significantly different (untreated 1.46 +/- 0.80 U/ml, treated 1.25 +/- 0.69 U/ml) and the mean logarithmic deviation of IGF-I plasma levels from both groups did not differ from normal. In summary, we found no abnormalities of the growth hormone-IGF-I axis in our patients with hypophosphatemic rickets. PMID- 8348223 TI - A case report: familial hypoalphalipoproteinemia. AB - We studied an 8 year-old girl whose height was 129 cm (25-50th percentile), weight 30 kg (75th percentile), blood pressure 115/75 mm Hg (75th percentile) and had a calcified mass lesion in the left posterior mediastinum. In the histopathological investigation of this mass lesion, symptoms of complicated atherosclerosis, such as mural thrombus and diffused calcification, were observed. Lipid investigations were performed in this patient whose total cholesterol and triglyceride levels were in the normal ranges. HDL-cholesterol, apoprotein A-I and alpha band were low without any other lipid and lipoprotein abnormalities. During one year, in her monthly lipid analysis the mean levels of HDL-cholesterol, apoprotein A-I and alpha band were found to be 0.73 +/- 0.11 mmol/l, 90 +/- 20 mg/dl and 23 +/- 5% respectively. Studies of her family revealed low levels of HDL-cholesterol, apoprotein A-I and alpha band in her mother and sister. We describe our investigation of this rare case of familial hypoalphalipoproteinemia. PMID- 8348224 TI - A case of mixed gonadal dysgenesis with 45 X/46 XY karyotype and aortic coarctation. AB - We report a case of mixed gonadal dysgenesis with 45 X/46 XY karyotype and aortic coarctation. An eight month-old patient was admitted to our endocrinology department for evaluation of ambiguous genitalia. On physical examination, a wide neck with a low posterior hairline, bifid scrotum, small phallus, testis in the right labioscrotal fold, single orifice and typical findings of aortic coarctation were present. The chromosome karyotype of the patient was 45 X/46 XY. On the laparotomy there was an infantile uterus, fallopian tubes, and a streak gonad on the left. The follow-up of the patient included sex assignment, genital reconstruction and cardiovascular treatment. PMID- 8348225 TI - Vaginal bleeding: presenting symptom of acquired primary hypothyroidism in a seven year-old girl. AB - A seven year-old girl who presented with vaginal bleeding and a right ovarian cyst was diagnosed as having acquired primary hypothyroidism. She had menstruation in spite of a delayed bone age, absence of pubertal growth spurt and lack of adrenarche. Elevated levels (age-matched) of gonadotropins, normal levels of estradiol, and hyperprolactinemia were documented. The clinical and laboratory findings were reversed by thyroxin treatment. The clinical presentation in this case, and other similar descriptions in the literature, support the mechanism of pseudo-precocious puberty in untreated hypothyroidism. PMID- 8348226 TI - Cushing's disease presenting as pubertal arrest. AB - The clinical features of Cushing's disease in childhood are usually abnormal fat distribution, moon face, growth failure and hirsutism. Laboratory studies include evidence of cortisol and ACTH hypersecretion. This report concerns a boy who presented only with arrested puberty and growth failure as physical evidence of Cushing's syndrome and showed rapid progression of puberty once pituitary adenomas were removed. PMID- 8348227 TI - A general strategy for glycoprotein oligosaccharide analysis. PMID- 8348228 TI - Analysis of bacterial glycoproteins. PMID- 8348229 TI - Isolation and fractionation of glycoprotein glycans in small amounts. PMID- 8348230 TI - High-mannose chains of mammalian glycoproteins. PMID- 8348231 TI - Release of O-linked glycoprotein glycans by endo-alpha-N-acetylgalactosaminidase. PMID- 8348232 TI - Immunological detection of glycoproteins on blots based on labeling with digoxigenin. PMID- 8348233 TI - Analysis of asparagine-linked oligosaccharides by sequential lectin-affinity chromatography. AB - Various immobilized lectins can be successfully used for fractionation and for structural studies of asparagine-linked sugar chains of glycoproteins (see Note 9). This method needs < 10 ng of a radiolabeled oligosaccharide prepared from a glycoprotein by hydrazinolysis or by digestion with endo-beta-N acetylglucosaminidases. The fractionation and the structural assessment through the use of immobilized lectins make the subsequent structural studies much easier. PMID- 8348234 TI - Glycosyltransferases as tools in cell biological studies. PMID- 8348235 TI - Purification of the EGF receptor for oligosaccharide studies. PMID- 8348237 TI - Secreted mucus glycoproteins in cell and organ culture. PMID- 8348236 TI - Analysis of sulfated polysaccharide conjugates. PMID- 8348238 TI - Preparation of polyclonal antibodies to native and modified mucin antigens. PMID- 8348239 TI - The application of lectins to the study of mucosal glycoproteins. PMID- 8348241 TI - Scanning tunneling microscopy of biopolymers. PMID- 8348242 TI - Sequence and linkage analysis of N- and O-linked glycans by fast atom bombardment mass spectrometry. PMID- 8348240 TI - Detection of tumor-associated expression of carbohydrate-binding proteins (lectins). The use of neoglycoproteins and neoglycoenzymes in glycohistochemical and glycocytological studies. PMID- 8348243 TI - Gas chromatography and gas chromatography-mass spectrometry of glycoprotein oligosaccharides. PMID- 8348244 TI - Microscale sequencing of N-linked oligosaccharides of glycoproteins using hydrazinolysis, Bio-Gel P-4, and sequential exoglycosidase digestion. PMID- 8348245 TI - Analysis of sugar chains by pyridylamination. PMID- 8348246 TI - Analysis of carbohydrates in glycoproteins by high-performance liquid chromatography and high-performance capillary electrophoresis. PMID- 8348247 TI - The microanalysis of glycosyl-phosphatidylinositol glycans. PMID- 8348248 TI - Low IgG4 concentrations in infants with Haemophilus influenzae type b infections. AB - Haemophilus influenzae type b causes considerable morbidity and mortality in infants and young children. Immunity to this organism has been attributed in part to the formation, and increase with age, of antibodies to the capsular polysaccharide of the bacteria. A degree of immunodeficiency could explain why some infants and young children develop invasive haemophilus disease. In this study we investigated immunocompetence in ten infants with invasive haemophilus disease. We found normal lymphocyte mitogen responses, neutrophil iodination and bactericidal and fungicidal capacities in this group. While we found no deficiencies of any of the immunoglobulin classes, three patients had low concentrations of IgG4 and two of them had low concentrations of IgG2 as well. These findings suggest that in some infants who develop haemophilus infections, the measurement of IgG subclasses may reveal immune defects that would not otherwise be apparent. PMID- 8348249 TI - Increase in platelet count following short course therapy with recombinant alpha 2b-interferon in immune thrombocytopenic purpura in childhood. AB - Two boys, aged three and seven years with immune thrombocytopenic purpura continued to show platelet counts below 20,000/mm3 inspite of treatment with high dose gammaglobulin and steroids. Alpha-2b-interferon injections were followed by normalisation of platelet counts in both patients. No side effects were seen. Alpha-interferon may be a safe and effective treatment for childhood-ITP. PMID- 8348250 TI - Development of immune response markers in the trachea in the fetal period and the first year of life. AB - Immunoglobulin (Ig)-producing cells, T cells (CD3) and epithelial expression of secretory component (SC) and HLA class II determinants (DR, -DP, -DQ) were studied by immunohistochemistry in 16 fetal and 15 postnatal specimens from the tracheal wall. Small amounts of secretory component (SC) was present in the tracheal surface and gland epithelium in the fetal period and increased towards term. A few IgM-, IgD- and IgG-producing cells were present in some fetal specimens but no IgA- and IgE-producing cells were found. Only very few CD3+ T cells were present in fetal specimens and intraepithelial T-cells were virtually absent until after birth. Premature infants that lived for 1 week had less SC epithelial expression than mature infants of the same age. The density of CD3+ T cells, IgA-, IgM-producing cells as well as the epithelial SC expression increased rapidly after birth. Epithelial MHC class II expression was absent in fetal specimens. HLA-DR was detected on the apical border of the surface epithelium one week after birth and was extensively expressed throughout the remaining postnatal period. Epithelial DP and PQ expression were virtually absent during this same period. These features probably reflect local activation of the immune system in response to environmental factors. PMID- 8348251 TI - Serum immunoglobulin G subclasses and serum immunoglobulin A in acute bronchiolitis in infants. AB - Serum IgG subclasses and Serum IgA were studied in 43 infants with acute bronchiolitis and 20 healthy infants. IgG subclasses were determined by a capture ELISA and IgA was quantified by turbidimetry. IgG1 concentrations were significantly lower in infants with bronchiolitis than in normal infants. The other IgG subclasses and IgA did not differ between the groups. The subgroups of infants with bronchiolitis who had previously suffered from otitis media or bronchitis, had significantly lower IgG2 than the other infants with bronchiolitis. The same was found for infants with bronchiolitis who had suffered from three or more lower respiratory tract infections. In infants who had suffered from upper or lower respiratory infections before the acute bronchiolitis, IgA was significantly higher than in infants without previous respiratory infections. Ten infants with bronchiolitis (23%) had IgG1 deficiency, that is values below the lower reference limit calculated in a population of healthy Norwegian infants. No healthy infants had any IgG1 deficiency. No infant with bronchiolitis had IgG2 or IgG3 deficiency. The low IgG1 values found in infants with acute bronchiolitis, may be one cause for infants to be more susceptible to RS virus infections. PMID- 8348252 TI - Responses of plasma vasoactive intestinal polypeptide to methacholine and exercise loading in children and adolescents with bronchial asthma. AB - Responses of plasma vasoactive intestinal polypeptide (VIP) to methacholine inhalation and to exercise loading were studied in asthmatic patients to clarify a significant role of the peptide. The mean of basal VIP in asthmatics was not significantly different from the normals. The levels were increased after FEV (1.0) (forced expiratory volume in a second) decreased to 80% of the baseline following methacholine inhalation and were returned to values similar to the baseline when FEV (1.0) recovered to 100%. Thirty minutes after the exercise, mean VIP was significantly lower in patients with the lowest FEV (1.0). These results suggest that VIPergic system contributes, at least partly, to relax constricted bronchioles in some patients with bronchial asthma. PMID- 8348253 TI - IgE levels in cord and capillary blood at 5 days of age. AB - We have determined the correlation between IgE in cord blood and capillary serum from 98 mature children at 5 days of age. Sixty-six per cent had no family history of atopy, 29% had a single and 5% a double disposition. The study showed a good correlation, rho = 0.75, p < 10(-5), between IgE levels in cord blood and capillary blood samples drawn on the 5th day of life in children both with and without a heredity of atopic diseases. There was no correlation between the concentrations of cord blood IgE and IgA. PMID- 8348254 TI - Prediction of allergy from family history and cord blood IgE levels. A follow-up at the age of 5 years. Cord blood IgE. IV. AB - Screening of total IgE in 1189 cord blood samples was conducted by Phadebas IgE PRIST in a one-year birth cohort 1983-1984 in Viborg, Denmark. 113 children with cord blood IgE levels > or = 0.5 kU/l and 138 children chosen at random among those with cord blood IgE levels < 0.5 kU/l were seen at a follow-up at 5 years of age. Based upon history and physical examination a diagnosis of definite atopy or no atopy was established. Allergy (IgE mediated) was defined as atopic disease combined with increased total IgE levels at 5 years of age. The cumulative prevalence of atopic disease was not influenced by cord blood IgE levels or atopic predisposition. Cord blood IgE levels had a low sensitivity as a predictor of atopic disease. A statistically significant correlation between serum levels of IgE at birth and at 5 years was however found (p < 0.001), and a significantly greater number of children with elevated cord blood IgE levels developed allergic disease before 5 years of age (p < 0.01). A cut-off limit of 0.3 kU/l was superior to the originally suggested limit of 0.5 kU/l. A total IgE level > 63 kU/l (geometric mean + 1 SD) at the age of 5 years can be regarded as being an elevated level. A cord blood IgE level > or = 0.3 kU/l in combination with atopic predisposition was predictive of allergic disease, especially allergic bronchial asthma. With regard to allergic disease, the positive predictive value was 26%, the sensitivity 33% and the rate ratio for development of allergic disease 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348255 TI - Immune defense to dietary cow milk in healthy infants. AB - The healthy young infant is immunologically adapted to receiving vast amounts of antigens in diet. At the age of 6 months, nine infants were put on a CM elimination diet for 3 weeks and then challenged with CM. Gut immune response was evaluated indirectly with ELISPOT assay at 6 months, after CM elimination (Day 1) and challenge (Day 8), and at 11 months. CM elimination decreased the numbers of immunoglobulin secreting cells (ISC): in the IgM class from mean [95% CI] 4969 [2555, 9653] at 6 months to 1716 [1024, 2873]/10(6) cells on Day 1 (t = 3.14, p = 0.01); and in the IgG class from 5547 [3562, 8630] to 2684 [1383, 5208]/10(6) cells (t = 3.29, p = 0.01). CM challenge further reduced inter-individual variation, and at 11 months the scatter of ISC was comparable to that at 6 months. Specific antibody-secreting cells of the IgA and IgG class were seen at 6 months and again at 11 months, while specific IgM-secreting cells persisted throughout the dietary manipulation. The results indicate that diet profoundly affects the immune defense system, and further suggest that a focused immune response is vital in acquisition of tolerance to dietary antigens. PMID- 8348256 TI - Multicenter study with ketotifen (Zaditen) oral drop solution in the treatment of wheezy children aged 6 months to 3 years. AB - One hundred and seven chronically wheezing infants, aged 6 months to 3 years, completed a double-blind placebo controlled multicenter study. After a two-week baseline period the patients were randomized into two groups receiving twice daily either ketotifen or placebo for a period of 12 weeks. The ketotifen dosage was 0.5 mg for children younger than one year and 1 mg for the older. During the 12-week treatment period the patients from the two groups demonstrated gradual improvement of the disease severity parameters, as compared with the baseline period. The amelioration was more marked in the ketotifen treated patients and during the 0-4, and 4-8 weeks of treatment a significant decrease was achieved in the percentage of days with a cough (p < 0.04) and in the number of wheezing episodes (p = 0.02). Moreover, a 50% reduction of the days and nights with cough and in the number of wheezing episodes occurred earlier in the ketotifen than in the placebo treated patients, i.e. after 1.2 vs 4.6; 4.4 vs 8.6 and 5.2 vs 7.2 weeks, respectively. It should be stressed that the amelioration of the asthmatic morbidity in the ketotifen group was achieved with a significantly reduced need for the concomitant use of bronchodilators. The principal side effects observed were weight gain and transient sedation. It is concluded that ketotifen may be effective in the amelioration of asthma associated symptomatology and acceleration in the natural tendency for improvement in chronic wheezing infants. PMID- 8348257 TI - Systemic meningococcal infections in patients with acquired complement deficiency. AB - Congenital deficiency of the late components of the complement may predispose the individual to systemic meningococcal infection. Assuming that patients with acquired complement deficiencies may also have an increased risk of contracting meningococcal infections, a retrospective and prospective study to assess this association was conducted. Over 20 years (1970-1989), 30 patients with meningococcemia or meningococcal meningitis, proven by blood or CSF culture, were treated at the Beilinson Medical Center. Only one patient died of the infection. Risk factors were found in three patients (10%). One had a congenital deficiency of C7, and two had acquired complement deficiency due to systemic lupus erythematosus (SLE) and membranoproliferative glomerulonephritis (MPGN). These latter two patients had low serum concentration of C3 and C4 and reduced complement hemolytic activity before onset of the infection. Since the incidence of culture-proven systemic meningococcal infection in the Jewish population in central Israel is 1/100,000, and the prevalence of SLE and MPGN is, at most, 250/100,000, the finding of two patients with meningococcal infection and these rare disorders is over 100 times the expected incidence. We conclude that patients with acquired complement deficiency are at significant risk of meningococcal infection. PMID- 8348258 TI - Sensitization and development of tolerance via the gut. PMID- 8348260 TI - Mechanisms of mucosal immunology and gastrointestinal damage. PMID- 8348259 TI - Age-related antibody response to food antigens. PMID- 8348261 TI - Intestinal permeability in children of different ages and with different gastrointestinal diseases. PMID- 8348262 TI - Fibre-optic techniques for investigation of gastrointestinal diseases in children. PMID- 8348263 TI - The immune system of the gastrointestinal tract. PMID- 8348264 TI - Markers of endothelial perturbation and damage. PMID- 8348266 TI - Antiribosomal P protein antibodies in different populations of patients with systemic lupus erythematosus. AB - We report a significantly increased prevalence of antiribosomal P protein antibodies in Malaysian Chinese patients (38%) with SLE compared to white Caucasian (13%) and Afro-Caribbean (20%) patients. The increased prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients. PMID- 8348265 TI - Effects of glucocorticoids and chronic inflammatory stress upon anterior pituitary interleukin-6 mRNA expression in the rat. AB - During development of adjuvant arthritis (AA) in the rat, anterior pituitary interleukin-6 (IL-6) mRNA expression was increased. Following adrenalectomy and AA there was a further increase in the accumulation of pituitary IL-6 transcript. Corticosterone (B) replacement in adrenalectomized (ADX) animals resulted in a dose-dependent reduction in pituitary IL-6 mRNA accumulation, while in ADX plus AA animals these effects of B were less marked. Cyclosporine A (CsA) markedly reduced the AA-induced increase in IL-6 mRNA. These data are consistent with an immunologically-mediated activation of pituitary IL-6 mRNA in AA, which may contribute to the increased activity of the pituitary-adrenal axis seen in this condition. PMID- 8348267 TI - Lymphocyte subpopulations analysis in peripheral blood in polymyalgia rheumatica/giant cell arteritis. AB - The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations. PMID- 8348268 TI - Mast cells in the synovium and synovial fluid in osteoarthritis. AB - SF and synovium from normal individuals and patients with OA, RA and traumatic arthritis (TA) were studied for the presence of mast cells (MC). When compared with normals, patients with OA had large numbers of intact and degranulated MC in the synovium and SF of diseased joints. The numbers of MC are comparable with those in RA where they have been implicated in the pathogenesis of joint damage. These data raise the possibility that in OA too MC may participate in the pathological processes in articular and periarticular tissues. PMID- 8348269 TI - Hepatitis C virus and essential mixed cryoglobulinaemia. AB - Clinical and laboratory evidence of liver involvement are frequently found in essential mixed cryoglobulinaemia (EMC). We looked for evidence of hepatitis C virus (HCV) infection in 37 patients with EMC. Anti-HCV antibodies (Ab) were found in 16/37 (43%) patients with EMC using the ELISA 2 test and the RIBA 2 test. The 16 anti-HCV-Ab positive patients (group 1) were compared to the 21 anti HCV-Ab negative patients (group 2). Group 1 patients had more frequent cutaneous involvement (P = 0.02), clinical, biological and histologic hepatic involvement (P < 0.01), higher serum cryoglobulin and lower CH50 levels (P < 0.001). Serum hepatitis B virus markers were infrequent in both groups and no patient from either group had detectable serum HBV DNA. These preliminary results suggest that HCV may be another cause of mixed cryoglobulinaemia. PMID- 8348270 TI - A controlled study of sacroiliitis in Behcet's disease. AB - Radiographs of the sacroiliac joints of 34 patients with Behcet's disease were read blind by a senior radiologist. They were compared with those from 25 controls, 14 of whom were healthy. The remainder (11) had other rheumatological disorders including six who had AS. One patient with Behcet's disease had radiologically proven sacroiliitis only but her history was atypical and she was B27 positive. All patients with AS had definite sacroiliitis. Five out of 34 patients with Behcet's disease and four of 25 controls (three healthy, one with SLE) had equivocal sacroiliitis. Whilst appreciating that the numbers in this study are not large, we find no evidence of an increased prevalence of sacroiliitis in Behcet's disease. PMID- 8348271 TI - Pyogenic sacroiliitis in Qatar. AB - We describe our experience in handling six cases of pyogenic sacroiliitis. Two were males and four were females with a mean age of 24.9 years. None had a history of i.v. drug abuse. Blood cultures were positive in half of the patients. The sacroiliac joint aspirate was positive in one additional patient. Staphylococcus aureus was recovered from three of four culture positive cases. Bone and CT scans revealed abnormalities in all patients. Response to antibiotic therapy was satisfactory in all except one patient who had an early relapse. Early diagnoses and proper treatment would result in improved outcomes. PMID- 8348272 TI - Sacral stress fracture after liver transplantation. AB - Sacral insufficiency fractures have been related to osteoporosis and steroid therapy, however only one case has been reported following liver transplantation. We describe three patients who developed insufficiency fractures of the sacrum following liver transplantation, these fractures could be overlooked or confused with inflammatory processes involving the sacrum. PMID- 8348273 TI - Intra-articular inclusions of the cervical synovial joints. AB - Two hundred and ten cervical synovial joints from 15 adult vertebral columns were studied by dissection to determine the form, dispositions and prevalence of intra articular inclusions. Three types of inclusions were found. Fat pads occurred regularly in the atlanto-occipital joints but rarely in the zygapophysial joints. Capsular rims occurred occasionally at all levels. Fibro-adipose meniscoid occurred regularly in the atlanto-axial and zygapophysial joints. The function of fibroadipose meniscoids seems to be to protect the articular cartilages in gliding joints that subluxate during normal movement. Arguments are raised that these structures may act as a nidus for intra-articular fibrosis, and that meniscus extrapment may be a mechanism for torticollis. PMID- 8348274 TI - Normal paraspinal muscle electromyographic fatigue characteristics in patients with primary fibromyalgia. AB - Paraspinal muscle fatigue mechanisms were compared in 14 primary fibromyalgia patients and 14 age and sex matched normal subjects using a standardized 60-s isometric endurance test of the paraspinal muscles, during which surface integrated electromyographic (IEMG) activity was recorded. Fatigue-induced IEMG increases were similar for both groups during the initial 40 s (up to 112 +/- 20% and 111 +/- 6% of initial values in patients and normal subjects respectively). Thereafter, IEMG fell significantly in patients (P < 0.05) but only slightly in controls, so that at 58 s IEMG was 102 +/- 13% in patients and 109 +/- 12% in controls. If patients were divided according to body mass index (BMI, range 19-25 in controls) those with a BMI < 26 (n = 5) showed IEMG changes similar to those of control subjects throughout the test, while obese patients with BMI > 26 (n = 9) showed greater IEMG declines after 40 s than either normal subjects or in the fibromyalgia group as a whole. Paraspinal muscle fatigue mechanisms appear normal in primary fibromyalgia patients. Isometric force maintenance in overweight patients, despite IEMG declines, illustrates the action of intrinsic fatigue resistance mechanisms which were presumably utilized to a greater extent in these patients to cope with the extra load. PMID- 8348275 TI - Factors predicting death, survival and functional outcome in a prospective study of early rheumatoid disease over fifteen years. AB - Sixty-four survivors from a prospective study of early rheumatoid disease were assessed again at a mean of 15.2 years from presentation and their status compared with 29 patients who had died. Eleven of the dead and only two of the survivors had been treated with steroids. There was a small increase in mortality due to the disease itself but only one death was directly caused by it. As might be expected, those who died were older. In the first year of disease, they had lower haemoglobin levels, a lower body mass, higher sedimentation rates and higher levels of blood urea. One-fifth at entry to the study and two-fifths by the time of death, had poor functional capacity. Of 64 survivors, six had poor functional capacity at entry and nine after 15 years. Discriminant analysis was performed to identify the most powerful combination of early features predicting a poor functional outcome. A combination including early erosive change, seropositivity, poor grip strength and cervical subluxation predicted the outcome correctly in 73% of survivors. Almost 60% of survivors remained with or improved to normal function at 15 years suggesting that morbidity is not as bad as has been suggested in the past. PMID- 8348276 TI - An evaluation of the Health Assessment Questionnaire in long-term longitudinal follow-up of disability in rheumatoid arthritis. AB - We have used the Health Assessment Questionnaire (HAQ) to follow changes in disability in an unselected group of 245 patients with RA. The HAQ has been widely used in cross-sectional studies of disability in RA, but little is known about the dynamics of the change in HAQ score with long term follow-up. If it is to prove useful as a measure of health outcome it must not only be able to accommodate a wide range of disability but also show adequate sensitivity to change in disability. We administered the HAQ to 245 RA inpatients and outpatients at the beginning and end of a 5-yr period to address this important question. The mean change in individual HAQ score in the 175 patients for whom complete data was available was +0.18 (SD 0.66) over 5 yr, i.e. 0.03 units per year. It is likely that the observed rate of change in HAQ score is an under estimate of the true rate of progression of disability, as the scale failed to accommodate change in disability toward its upper limit. The inherent design of the HAQ creates several 'ceilings' in functional subcategories (such as lower limb function) which may be masked by the overall HAQ score. Longitudinal studies of disability using the HAQ as outcome measure should therefore be interpreted with caution, and close attention paid to the baseline HAQ score. PMID- 8348277 TI - Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the induction phase of chrysotherapy. AB - In a randomized double-blinded placebo-controlled trial, 41 patients with RA starting on i.m. sodium aurothiomalate (SAT) therapy were randomized to receive three doses of either 500 mg methylprednisolone (MP) orally and a placebo injection or 120 mg of i.m. depot methylprednisolone acetate (MPA) and oral placebo tablets at 4-weekly intervals. Disease activity was assessed by visual analogue scale (VAS) of pain, grip strength (GS), tender joint count (JC), and Health Assessment Questionnaire (HAQ). Laboratory assessment was by haemoglobin concentration (Hb) and ESR. A composite index of Disease Activity score (IDA) was constructed using all six measurements. The group receiving i.m. MPA showed greater improvement when compared with the group receiving oral MPA. These changes were statistically significant (P < 0.05) for ESR (weeks 2, 6, 8, 10, 12), VAS (week 4, 6, 8), JC (weeks 2, 4, 6, 8, 10) and HAQ (weeks 2, 8, 10). Statistically significantly (P < 0.05) greater improvement in Hb was seen throughout all time points in favour of the group treated with i.m. MPA. Using the IDA score to summarize the results, patients treated with i.m. MPA had better disease remission from weeks 2-12. In all measures, except Hb, no statistically significant difference between the two groups was seen by 16 weeks. We conclude that 120 mg i.m. depot MPA is more effective at inducing improvement in disease activity than 500 mg of oral MPA in RA patients starting on SAT therapy. PMID- 8348278 TI - A double-blind study of the effectiveness of low level laser treatment of rotator cuff tendinitis. AB - Thirty-five patients with rotator cuff tendinitis were randomly allocated to active (CB Medico Master III 830 nm Ga As AL diode) laser or dummy laser treatment twice weekly for 8 weeks. Movement range, painful arc score, resisted movement score and responses to visual analogue scales for night pain, rest pain, movement pain and functional limitation were measured second weekly. All responses improved from baseline but there was no difference between the two groups. These results fail to demonstrate the effectiveness of laser therapy in rotator cuff tendinitis. PMID- 8348279 TI - A double-blind trial comparing subacromial methylprednisolone and lignocaine in acute rotator cuff tendinitis. AB - Fifty-five patients with shoulder pain due to rotator cuff tendinitis of less than 12 weeks' duration were randomized to receive either 40 mg methylprednisolone and lignocaine or lignocaine alone. No statistically significant difference could be discerned between the two groups during 12 weeks of follow-up. PMID- 8348280 TI - A 6-month randomized dose range study of OM-8980 in rheumatoid arthritis. AB - Sixty patients with active RA were evaluated over 6 months in a double-blind randomized dose range multicentre study comparing the efficacy and tolerance of three different doses of the slow-acting anti-rheumatic bacterial extract OM-8980 (6, 24 and 48 mg of active principle). No patients were withdrawn during the study. At the end of the 6-month trial, significant improvements were observed for the different RA signs and symptoms (Ritchie index, morning stiffness, swollen joints, grip strength, ESR, pain scale and categories) as well as for the concomitant intake of symptomatic drugs in the 24-mg dose group with respect to the 6-mg group and without significant differences between the 24- and 48-mg groups. Tolerance was very good with nine minor and transient side effects (five itching and four diarrhoea) reported altogether by seven patients, without establishment of a dose-effect correlation. In conclusion, the two higher doses of OM-8980, 24 and 48 mg, were significantly more efficient than 6 mg, with the effect of the 24-mg dose being even slightly superior to the 48-mg dose, confirming the former as the optimal and well-tolerated dose for the treatment of RA. PMID- 8348282 TI - Recurrent polyarthritis in a young woman with an ileoanal pouch for ulcerative colitis. PMID- 8348281 TI - Methotrexate--the relationship between dose and clinical effect. AB - Methotrexate (MTX) is an effective anti-rheumatic drug. Despite its frequent use, the relationship between different MTX doses and clinical effects remain unclear. In a randomized double-blind study in patients with RA, the effects of four MTX doses (5 to 20 mg) was studied. MTX (5 mg) induced a significant effect on the Ritchie joint index, morning stiffness, pain, ESR and C-reactive protein. The effect of MTX on those variables was related to the dose in the range from 5 to 20 mg MTX weekly. Interindividual differences in dose-response curves were observed. The study shows that MTX doses should be adjusted individually for each patient in order to improve efficacy and decrease dose-dependent side effects. PMID- 8348283 TI - Chronic idiopathic mediastinal fibrosis presenting with malaise, pleuritis and thoracic back pain. AB - A patient with chronic idiopathic mediastinal fibrosis (MF) without concomitant retroperitoneal fibrosis is reported. He presented with pleuritis, malaise and pain and stiffness in the thoracic spine. During the 3.5 years of observation no clinical signs of obstruction of adjacent visceral structures in the chest cavity have developed. The diagnosis was made by CT, X-rays of the chest remained normal throughout the observation period, except for thickening of the involved pleura. The administration of high doses of oral corticosteroids did not appear to influence either clinical symptoms or the manifestations of MF as seen by CT. PMID- 8348284 TI - Sclerotherapy as treatment of recurrent bleeding from upper gastrointestinal telangiectasia in CREST syndrome. AB - A case of CREST syndrome is reported with recurrent bleeding from oesophageal telangiectasia which required repeated blood transfusions. No other cause for the haemorrhage was found. This complication was effectively treated by sclerotherapy with no recurrence of bleeding over a 12-month period of follow up. PMID- 8348285 TI - British Society for Rheumatology meeting report. Special interest group for orthopaedic medicine/soft tissue rheumatism. 26 March 1992. PMID- 8348286 TI - Differentiating persistent from self-limiting symmetrical synovitis in an early arthritis clinic. PMID- 8348287 TI - Abnormal fibrinolysis in chronic low back pain. PMID- 8348289 TI - Muscular involvement in systemic rheumatoid vasculitis. PMID- 8348288 TI - Necrotizing glomerulonephritis as a complication of rheumatoid arthritis vasculitis. PMID- 8348291 TI - Salmonella lomita spondylodiscitis. PMID- 8348290 TI - Effects of intravenous aminopropylidene bisphosphonate in patients with refractory Paget's disease. PMID- 8348292 TI - Metabotropic receptor stimulation coupled to weak tetanus leads to long-term potentiation and a rapid elevation of cytosolic protein kinase C activity. AB - We have previously shown that short-term potentiation (STP) inducing weak tetanus induces long-term potentiation (LTP) when it is coupled with activation of metabotropic glutamate (mGlu) receptors by trans-(+/-)-1-amino-1,3 cyclopentanedicarboxylic acid (t-ACPD) in rat CA1 slices. In the present study, we examined if this conversion of STP to LTP involves activation of protein kinase C (PKC). Two minutes but not 30 min after coupling, there was a significant increase in the activator-dependent PKC activity in the cytosolic fraction. STP induction or t-ACPD application did not change PKC activity. There was no activity increase in the membrane fraction. STP was also induced by a co application of gamma-amino-3-hydroxy-5-methyllisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA). Coupling this STP with t-ACPD, however, did not result in an LTP or PKC activity increase, indicating a requirement for synaptic activity. A rapid and transient (< 5 min) increase in cytosolic PKC activity was also seen after the induction of LTP by stronger tetanic stimulation. No LTP tested in the present study was accompanied by activator independent, persistent increases in PKC activity. STP induction depends on NMDA receptor activation, and the activation of mGlu receptors results in the production of intracellular second messengers. Our results therefore indicate that these separate components may add and bring about PKC activation and LTP. PMID- 8348294 TI - Regional and temporal variations in the accumulation of unesterified fatty acids and diacylglycerols in the rat brain during kainic acid induced limbic seizures. AB - These experiments tested the hypothesis that limbic seizures induced by kainic acid (KA) activate mechanisms (e.g. phospholipase) that degrade the cell membrane, causing a release and accumulation of free fatty acids (FFAs) and diacylglycerols (DGs) in brain areas susceptible to seizure-related damage. The possible link between these effects on lipids and the subsequent development of seizure-related brain damage was investigated by studying the temporal and regional relationship between alterations in lipids in the hippocampus, frontal cerebral cortex, amygdala, striatum and cerebellum, and the development and severity of seizures. Rats were treated with 10 mg/kg KA (s.c.) and sacrificed by head focused microwave irradiation at 1 h, 2 h, 24 h, or 7 days. Levels of FFAs and DGs were determined by gas liquid chromatography (GLC). Brain regions from control rats differed markedly in the content and composition of both FFA and DG pools. Changes in FFAs and DGs during KA-induced limbic seizures also varied from region to region and over time after drug treatment. The largest increases in FFAs in amygdala, striatum, cortex and hippocampus occurred during the peak of seizure activity. Although DG levels were altered in some areas at some time points, there was no apparent correlation between changes in DGs and seizure severity. However, increases in DGs occurred at later time points, coincident with the occurrence of neuronal cell loss in amygdala, cortex, hippocampus and striatum. These data indicate that limbic seizures activate the accumulation of FFAs through increased neuronal activity, while accumulation of DGs may be related to the development of seizure-related brain damage. PMID- 8348293 TI - Taurine transport in rat astrocytes adapted to hyperosmotic conditions. AB - [3H]Taurine uptake and release was characterized in astrocytes from rat cerebral cortex grown in normal and hyperosmotic culture conditions to investigate mechanisms of cell volume regulation and adaptation to states of altered osmolality. In high concentrations of taurine (1 mM), uptake was linear in both osmotic conditions for at least 30 min. The uptake rate in 1 mM taurine was not affected by exposure to hyperosmotic conditions. The mean +/- S.E.M. apparent binding constant for carrier-mediated taurine transport, Km, was not altered by hyperosmotic conditions (22.8 +/- 5.1 microM in iso-osmotic media, 21.3 +/- 11.9 microM in hyperosmotic media). However, maximal velocity of uptake, Vmax (mean +/ S.E.M.), of taurine was significantly lower in hyperosmotically treated astrocytes (0.175 +/- 0.035 nmol/mg protein.min) compared with the Vmax of iso osmotically treated astrocytes (0.299 +/- 0.026 nmol/mg protein.min). The diffusional transport rate, Kdiff, was not affected by growth in hyperosmotic conditions (0.221 +/- 0.033 microliter/mg protein.min in iso-osmotic media, 0.295 +/- 0.043 microliter/mg protein.min in hyperosmotic media). Taurine release rate, expressed as a percent of the total cell content, was not affected by hyperosmotic exposure. However, astrocytes grown in hyperosmotic conditions contain nearly 60% more taurine than control cells. Thus, the absolute rate of taurine release (mean +/- S.E.M.) was significantly larger (P < 0.05) in hyperosmotic cells (0.1592 +/- 0.0082 nmol/mg protein.min) compared with control cells (0.0943 +/- 0.0096 nmol/mg protein.min). Quantitative analysis of these data indicate that maintenance of elevated taurine contents by cultured cerebral astrocytes exposed to hyperosmotic conditions is not due to alterations in rates of transport. PMID- 8348295 TI - Neuronal 'differentiation' of murine neuroblastoma cells induced by neocarzinostatin: neural cell adhesion molecules. AB - Neural crest tumor cells which have been pharmacologically induced in culture to undergo neuronal 'differentiation' have been proposed as a model for normal neural crest cell differentiation. We have previously reported that murine neuroblastoma cells treated with the antineoplastic agent neocarzinostatin (NCS) adopt the light microscopic appearance of differentiated neurons. After undergoing morphologic change, the cells no longer divide. As part of an effort to compare the process of differentiation in these cells with what is known about normal neural crest cells, we have examined the cellular distribution and isoform complement of neural cell adhesion molecules (NCAMs) in native and NCS-treated neuroblastoma cells. Our studies show that NCS induces profound changes in NCAM distribution. Immunohistochemical staining indicates that, in contrast to native neuroblastoma cells, more than 80% of treated cells display surface NCAM by 4 days following treatment. Unlike the case for normal neurons, NCAM is uniformly distributed over the treated cell surface. Neuroblastoma cells treated with NCS are more avidly adherent to culture plates coated with NCAM than are control neuroblastoma cells, reflecting the homophilic binding characteristics of NCAM. Interestingly, Western blot analysis for NCAM demonstrates similar total cellular content of a single NCAM species in both control and treated neuroblastoma cells. Furthermore, this 120 kDa mol. wt. NCAM is an isoform of NCAM not found on normally differentiated cerebellar neurons. While the presence of NCAM on these treated murine neuroblastoma cells is evidence for 'differentiation' along neuronal lines, the isoform complement and cell surface distribution of NCAM in treated cells are not normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348296 TI - Interleukin-1 beta inhibits the endogenous expression of the early gene c-fos located within the nucleus of LH-RH neurons and interferes with hypothalamic LH RH release during proestrus in the rat. AB - The ability of central interleukin-1 beta (IL-1 beta) administration to modulate the hypothalamic LH-RH release as well as the endogenous expression of the c-fos protein located within the nucleus of LH-RH neurons was examined during the afternoon of proestrus in rats. In a first series of experiments, 50 or 100 ng IL 1 beta were infused into the lateral ventricle of the rat brain at either 08.30, 12.00, 14.30, or 17.00 h of proestrus. The animals were then perfused transcardially with a solution of 4% paraformaldehyde from 17.30 and 18.00 h. In a second series of experiments, the rats were equipped with an intracerebroventricular (i.c.v.) cannula in the lateral ventricle and a push-pull cannula into the median eminence (ME), and LH-RH secretion was measured during the afternoon of proestrus. The third experiment investigated the putative role of corticotropin-releasing factor (CRF) in modulating the inhibitory effect of IL 1 beta on LH secretion by infusing CRF antagonists before the i.c.v. administration of the cytokine to gonadectomized male and female rats. The central infusion of 50 or 100 ng IL-1 beta at 12.00 h completely blocked the spontaneous expression of c-fos protein which normally occurs in the nucleus of LH-RH neurons between 17.30 and 18.00 h on proestrus. In contrast, 50 ng IL-1 beta was less effective (P < 0.05) when administered at 08.30 h, and totally without effect when infused at 14.30 h. Infusion of 50 ng IL-1 beta also markedly suppressed the hypothalamic release of LH-RH in proestrus rats bearing a push pull cannula into the ME, and significantly decreased plasma LH levels in both gonadectomized male and female rats. Finally, we observed that the central administration of CRF antagonists did not modify the inhibitory effects of the cytokine on the activity of the hypothalamic-pituitary-gonadal (HPG) axis. These results provide the first direct evidence that IL-1 beta is a potent inhibitor of LH-RH neuronal activity during the proestrus LH surge in intact cycling rats. As central administration of this cytokine completely inhibited the endogenous expression of c-fos protein within the nucleus of LH-RH neurons, our findings also suggest that IL-1 beta acts at the level of LH-RH perikarya. PMID- 8348297 TI - Histamine phase shifts the circadian clock in a manner similar to light. AB - The mammalian circadian pacemaker in the suprachiasmatic nuclei (SCN) receives a dense input from histamine-containing neurons in the posterior basal hypothalamus. We applied histamine to SCN tissue in vitro and measured the subsequent rhythm in firing rate. Histamine caused a phase delay in the early subjective night and a phase advance in the late subjective night. The similarity of histamine- and photic-induced phase shifts indicates that histamine may play a role in the modulation of circadian clock photic input. PMID- 8348298 TI - Neurons in the inferior colliculus, auditory cortex and pontine nuclei of the FM bat, Eptesicus fucus respond to pulse repetition rate differently. AB - Single-neuron responses to pulse repetition rate in the inferior colliculus, auditory cortex and pontine nuclei of the FM bat, Eptesicus fuscus were studied under free-field stimulation conditions. The best frequency (BF) and minimum threshold (MT) of each neuron were first determined with a 4 ms pulse broadcast from a specific point (response center) of the bat's frontal auditory space at which the neuron had maximal spatial sensitivity. The neuron's intensity-rate function was then studied with a 4 ms BF pulse delivered at 10 dB increments above its MT in order to determine the best intensity to which the neuron discharged maximally. The neuron's discharge pattern and number of impulses to 32 trials of 300 ms train stimuli, which consisted of different number of 4 ms BF and best intensity pulses (1, 2, 3, 8, 12, 19, 24, 29 pulses/train) and delivered at an interpulse interval of 1000, 250, 170, 100, 40, 25, 15, 12 and 10 ms (i.e. at a pulse repetition rate of 1, 4, 6, 10, 25, 40, 67, 83, 100 pulses/s), were sequentially recorded. All neurons recorded from the inferior colliculus, auditory cortex and pontine nuclei discharged phasically (1-3 impulses) but they responded to the pulse repetition rate in different manners. More than 63% of 38 inferior collicular and 65 pontine neurons studied discharged impulses to each pulse within a train stimulus when the pulse repetition rate was up to 40 pulses/s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348299 TI - Changes in extracellular adenosine during chemical or electrical brain stimulation. AB - The purpose of this study was to determine the changes in adenosine and adenosine metabolites during graded electrical stimulation or kainic acid-induced activation and to assess the role of adenosine in the cerebral blood flow (CBF) response to increased brain activity. A modified brain microdialysis technique was used to sample cerebral interstitial fluid (ISF), deliver drugs locally to the brain, electrically stimulate the brain, and measure local CBF (H2 clearance). Microdialysis probes were implanted bilaterally in the caudate nuclei of ketamine-anesthetized rats. Graded electrical stimulation at 5, 15, and 30 Hz increased dialysate adenosine 1.5-fold, 2.3-fold, and 4.7-fold, respectively. Local infusion of kainic acid, an agonist of the excitatory amino acid neurotransmitter glutamate, produced a transient increase (2-fold) in dialysate adenosine and sustained increases in dialysate inosine (2-fold), hypoxanthine (4 fold) and CBF (2.4-fold). When the adenosine receptor antagonist 8(p sulphophenyl)-theophylline (SPT, 10(-3) M) was co-administered with kainic acid, CBF increased only 1.6-fold, while the increase in dialysate adenosine was augmented by 40%. These data demonstrate that ISF adenosine increases during brain activation and suggest that adenosine contributes to active hyperemia in the brain. PMID- 8348300 TI - Interleukin-1 beta, but not interleukin-6, impairs spatial navigation learning. AB - The effects of the cytokines interleukin-1 and -6 (IL1 beta, IL6; 100 ng) on spatial learning were examined in the Morris water maze. Intracerebroventricular injection of IL1 or IL6 before the training on day 1 did not influence the acquisition of spatial navigation. However, IL1 administered at 60 min, but not immediately before the training, resulted in impaired performance of spatial navigation the following day. In contrast, IL6 administered at both times had no effect. In a second experiment the same doses of IL1 and IL6 increased the body temperature of rats in a time-related fashion. The temperature effect of IL1 developed after a delay of 120 min, while the IL-6-effect was immediate. Comparable behavioral changes might accompany infections or inflammatory diseases and therapeutic cytokine administration. PMID- 8348301 TI - 2-Mercaptoethanol is a survival factor for olfactory, cortical and hippocampal neurons in short-term dissociated cell culture. AB - A medium originally designed for lymphocyte growth promoted robust survival of olfactory receptor neurons (ORNs) in short-term (4-day), dissociated cell culture. The key ingredient for survival of neurons in both serum and serum-free conditions was 2-mercaptoethanol (2-ME). Enhancement of survival may be thiol mediated because two other thiol compounds, 2-mercaptoethylamine and monothioglycerol, also increased ORN survival. Addition of 2-ME also significantly increased survival of embryonic cortical and hippocampal neurons in a serum-free medium, and embryonic cortical neurons in a serum-containing medium. After plating and growth in a serum-free medium containing 2-ME, survival of all three types of neurons was equivalent to, or greater than, survival in serum containing media. Thus, thiols such as 2-ME promote the survival of multiple types of neurons in short-term cell culture. PMID- 8348302 TI - The zitter rat: membranous abnormality in the Schwann cells of myelinated nerve fibers. AB - Ultrastructural alterations of the Schwann cells were chronologically examined in zitter and in control rats. The membranous abnormalities closely involving the nuclear membranes of the Schwann cells and mesaxons were constantly observed in the zitter rats. These structures consisted of scroll- or whirl-like unit membrane accumulations directly extending to the nuclear envelope. Occasionally, similar membranous structure were observed in association with the endoplasmic reticulum, lysosome or mitochondria in the cytoplasm of the Schwann cells. In the control rats, whirl-like membranous structures in the nuclear membranes of the Schwann cells were observed only intermittently at 1, 5 and at 7 days of age in the developing process. In conclusion, we postulate that the zitter rat, which is an established animal model for hypomyelination of the central nervous system (CNS), has some inherited abnormality related to the membrane biosynthesis and its regulation in Schwann cells as well as in oligodendrocytes. PMID- 8348303 TI - Electrotonic coupling between neurosecretory cells in the crayfish eyestalk. AB - Electrical coupling is described among neurosecretory cells in the crayfish X organ. By simultaneous impalements from pairs of neurons, only 30% were found to be coupled. All of them showed non-rectifying junctions. In all cases, electrical coupling corresponded to dye-coupling, as explored with intracellular injection of Lucifer yellow to one of the recorded cells. Some neurons were coupled to more than one neighbour. From dye fills it was apparent that the coupling site could be located far away from the cell body, immediately before the axonal branchings in the neuropile. The input resistance of the coupled neurons was consistently lower (24 +/- 16 M omega) than that of the non-coupled neurons (58 +/- 18 M omega). Synchronous synaptic activity was commonly recorded from coupled neurons, thus suggesting a functional significance of coupling in the integration of neurosecretory activity. PMID- 8348304 TI - Protein kinase inhibitors do not block the expression of established enhancement in identified Hermissenda B-photoreceptors. AB - One-trial conditioning of Hermissenda produces short- and long-term enhancement of generator potentials in identified type B-photoreceptors. The induction of short-term enhancement is blocked by kinase inhibitors and down-regulation of protein kinase C. We now report that established short- and long-term enhancement produced by one-trial conditioning is not reversed by the kinase inhibitors H-7 or sphingosine. These results indicate that persistent protein kinase C activity is not required in the maintenance or expression of enhancement. PMID- 8348305 TI - Regulation of astrocyte proliferation by prostaglandin E2 and the alpha subtype of protein kinase C. AB - We found that astrocytes expressed the alpha subtype of protein kinase C. Treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) caused cultured astrocytes to proliferate. This effect of TPA was blocked by staurosporine, a potent protein kinase C inhibitor, suggesting the involvement of protein kinase C in astrocyte proliferation. Indomethacin, an inhibitor of prostaglandin formation, enhanced both the normal and TPA-induced proliferation of astrocytes. Authentic prostaglandin E2 blocked this effect of indomethacin and also partially blocked the effect of TPA, suggesting that the intracellular mechanisms involved in prostaglandin E2-regulated astrocyte growth might differ from those acting in protein kinase-dependent growth. The effect of prostaglandin E2 was blocked by a specific anti-prostaglandin E2 polyclonal antibody. Cultured astrocytes and microglia produced and released prostaglandin E2 in response to stimulants such as lipopolysaccharide, TPA, and lymphokines. Since the sensitivity of astrocytes and microglia to these stimuli was different, prostaglandin E2 may differentially regulate astrocyte proliferation under different physiological conditions, acting in an autocrine fashion for astrocytes and in a paracrine fashion for microglia. PMID- 8348307 TI - Angiotensin II in the spinal cord of the rat and its sympatho-excitatory effects. AB - Immunohistochemical studies have shown there is a dense angiotensin-like immunoreactivity of terminals in the sympathetic region of the thoracic and lumbar spinal cord. In the present study measurements were made of the concentration of angiotensin in the spinal cord of rats using radioimmunoassay following two different extraction procedures. These gave concentrations of angiotensin as mean of 108 and 161 pg.g-1 tissue wet weight. Angiotensin II given intrathecally or microinjected into the spinal cord caused an increase in postganglionic sympathetic nerve activity which was blocked by prior application of saralasin. Angiotensin III was without effect. Intracellular recordings from sympathetic preganglionic neurones in-vitro in slices of neonate rat spinal cord showed that angiotensin II produced an increase of excitability of the neurones by a slow depolarisation without the generation of action potentials. This effect still occurred in the presence of TTX. Angiotensin II also could increase synaptic activity, both EPSPs and IPSPs as well as a synaptically induced slow depolarisation being observed suggesting that presympathetic interneurones are also sensitive to the peptide. The evidence indicates that if angiotensin is released from nerve terminals surrounding sympathetic neurones it will enhance the gain of the neurone so that it could more easily be discharged by other excitatory inputs. PMID- 8348306 TI - B-50 (GAP-43) in Onuf's nucleus of the adult cat. AB - The nucleus of Onuf in the sacral spinal cord contains motoneurons that innervate the pelvic floor muscles and possess somatic and autonomic characteristics. We show in this study that in the intact adult cat, the immunocytochemical labelling of the nervous tissue-specific growth-associated protein, B-50 (GAP-43), which persists in Onuf's nucleus, differs markedly from that in the remaining 'purely somatic' motor nuclei of the sacral spinal cord. At the light microscopic level, an intense B-50 (GAP-43) immunoreactivity (B-50-IR) in the neuropil of Onuf's nucleus contrasts with a faint staining in the other spinal motor nuclei. Ultrastructurally, B-50-IR is found in Onuf's nucleus within some unmyelinated small diameter nerve fibres and numerous axon terminals on dendritic and somatic surfaces. Conversely, in all other motor nuclei only a few of these structures are stained. No other cellular profiles show B-50-IR in the tissue examined. According to the proposed functions of B-50 (GAP-43), its persistence in mature spinal axon terminals may indicate a latent capability of functional and structural remodeling, as well as an involvement in long-term enhancement in synaptic transmission. If so, these properties would be considerably more pronounced in Onuf's nucleus as compared to purely somatic motor nuclei. PMID- 8348308 TI - p34cdc2 homologue is located in nucleoli of the nervous and endocrine systems. AB - p34cdc2 protein kinase is a component of M phase-promoting factor (MPF), which plays an important role in controlling the mitotic and meiotic cell cycle. p34cdc2 contains a unique 16 amino acid sequence (PSTAIR) that is conserved from fission yeast to human. Using polyclonal anti-PSTAIR antibody, we detected the p34cdc2 homologue in the central nervous system of adult mice by western blotting. By immunohistochemical technique, we found that the p34cdc2 homologue was located in the nucleoli of neurons and glia in the central and peripheral nervous systems. In the central nervous system, positive cells were widely distributed from the cerebral cortex to the spinal cord. Immunoreactive cells were also detected in retina and pituitary. The evidence that the p34cdc2 is present in neurons which have lost the ability of cell division predicts another function of p34cdc2 family proteins besides the one that has generally recognized. PMID- 8348310 TI - Elevated concentrations of nerve growth factor in heart and mesenteric arteries of spontaneously hypertensive rats. AB - Considerable evidence indicates an enhanced sympathetic innervation of muscular resistance arteries in the spontaneously hypertensive rat (SHR) compared with its normotensive Wistar-Kyoto (WKY) control. Since nerve growth factor (NGF) is known to affect the growth of sympathetic nerves, we have utilized a sensitive two-site enzyme linked immunoassay for NGF to compare the NGF content of hearts and mesenteric arteries of developing SHR and WKY rats. NGF levels in hearts revealed similar, although not identical, patterns of expression. In both strains, NGF levels declined from postnatal day 15, the earliest age examined, to stabilize at adult levels by postnatal day 32. Adult SHR concentrations were similar to those in age matched WKY controls. In contrast, in the mesenteric vascular bed, NGF levels of SHR were greater than those of WKY controls at all ages above 15 days. Moreover, these changes in NGF occurred concomitantly with increases in vascular mass and medial smooth muscle hyperplasia in the SHR. Whether abnormal NGF levels are a cause or consequence of vascular smooth muscle growth has yet to be determined. These results are consistent with the hypothesis that the hyper noradrenergic innervation of SHR vascular tissues results from an early elevation of NGF gene expression. PMID- 8348309 TI - Protection of the axonal cytoskeleton in anoxic optic nerve by decreased extracellular calcium. AB - Since CNS white matter tracts contain axons, oligodendrocytes and astrocytes but not synapses, it is likely that anoxic injury of white matter is mediated by cellular mechanisms that do not involve synapses. In order to test the hypothesis, that anoxic injury of white matter is mediated by an influx of Ca2+ into the intracellular compartment of axons, we compared the ultrastructure of axons in rat optic nerve exposed to 60 min of anoxia in artificial cerebrospinal fluid (aCSF) containing normal (2 mM) Ca2+, and in aCSF containing zero-Ca2+ together with 5 mM EGTA. Optic nerves fixed at the end of 60 min of anoxia in 2 mM Ca2+ exhibit extensive ultrastructural alterations including disruption of microtubules and neurofilaments within the axonal cytoskeleton, development of membranous profiles and empty spaces between the axon and the ensheathing myelin, and swelling of mitochondria with loss of cristae. Bathing the nerves in zero Ca2+ aCSF during anoxia protected the axons from cytoskeletal changes; after 60 min of anoxia, optic nerve axons retained normal-appearing microtubules and neurofilaments. Membranous profiles were rare, and empty spaces between axons and myelin did not develop in anoxic optic nerves bathed in zero-Ca2+ aCSF. Disorganization of cristae in axonal mitochondria was observed in anoxic optic nerves even when Ca2+ was omitted from the medium. Because Ca(2+)-mediated injury is known to disrupt the axonal cytoskeleton, these results support the hypothesis that anoxia triggers an abnormal influx of Ca2+ into myelinated axons in CNS white matter. PMID- 8348312 TI - The paraventricular nucleus is uniquely responsive to the feeding stimulatory effects of steroid hormones. AB - The paraventricular nucleus is uniquely responsive to the feeding stimulatory effects of steroid hormones (Tempel, D.L., Kim, T. and Leibowitz, S.F. Brain Research 00: 000-000). This study tested the effects of hypothalamic as well as extrahypothalamic implants of the adrenal steroids, corticosterone (CORT) and aldosterone (ALDO), on food intake and macronutrient selection in sham-operated and adrenalectomized (ADX) rats 1 h after administration. Consistent with a previous experiment, implants of CORT and ALDO in the hypothalamic paraventricular nucleus (PVN) were effective in stimulating food intake. These tests, conducted at the onset of the active feeding cycle, showed PVN implants of CORT to potentiate specifically carbohydrate intake in ADX rats, while having no effect in sham rats. This was in contrast to PVN ALDO which predominantly stimulated fat intake in sham as well as ADX rats. Neither CORT nor ALDO had any effect on food intake after implantation into other hypothalamic or extrahypothalamic sites tested. These unresponsive hypothalamic sites were the dorsomedial and ventromedial nuclei, perifornical lateral hypothalamus, and arcuate nucleus. Extrahypothalamic sites including the dorsal CA1 region of the hippocampus, the central nucleus of the amygdala and the lateral septum were also unresponsive to steroid implants. These results identify the PVN, and the steroid receptors located within it, as having a specific function in mediating the action of CORT and ALDO on carbohydrate and fat intake, respectively. PMID- 8348311 TI - Regional blood-brain lactate influx. AB - Regional blood-to-brain lactate transport was studied in chloral hydrate anesthetized rats using the single pass, dual-label, indicator fractionation, right atrial injection method. Lactate influx was resolved into two components, a saturable, stereospecific (to the L-enantiomer) component and a non-saturable, non-stereospecific diffusional component. The saturable component was found to have a low efficiency and moderate capacity with transport affinity coefficients between 6 and 14 mM and transport maxima of 23-40 mumol/100 g/min in the various brain regions. Lactate transport was not inhibited by probenecid. The diffusional component was determined from D-lactate influx measurements and the regional linear diffusion coefficients ranged from 0.020 to 0.036 ml/g/min. At the usual levels of plasma lactate (1-1.5 mM) these two influx components were about equal. The relative contribution of the non-stereospecific diffusional component was increased at higher plasma lactate concentrations. Lactate clearance, estimated by the total apparent permeability x surface area products was between 6 and 8 ml/100 g/min. PMID- 8348313 TI - Hyposmotic activation hyperpolarizes outer hair cells of guinea pig cochlea. AB - The electrophysiological responses of isolated guinea pig outer hair cells (OHCs) to hyposmotic activation were studied using the whole-cell patch-clamp technique. The cell swelling by hyposmotic activation hyperpolarized OHCs by 6.6 +/- 2.3 mV from the resting membrane potential of -58.5 +/- 5.9 mV (n = 48). This hyperpolarization was associated with an outward current (97.7 +/- 22.2 pA, n = 15). The hyperpolarization was inhibited by 300 microM quinine, 5 mN Ba2+ and increasing the extracellular K+ to 30 mM from 5 mM. In the absence of extracellular Ca2+ (1 mM EGTA), the hyperpolarization during hyposmotic activation was also abolished while the following depolarization was preserved. 50 microM GdCl3, which is known to block stretch-activated non-specific cation channels, inhibited the hyperpolarization reversibly. 50 microM GdCl3 also inhibited [Ca2+]i increase during hyposmotic activation as shown by the calcium sensitive dye fura-2. Simultaneously, the [Ca2+]i increase and the hyperpolarization during hyposmotic activation could be observed using the combined method of whole-cell patch clamp and fura-2 technique. It is concluded that the cell swelling by hyposmotic activation may activate the stretch activated non-specific cation channels in the OHCs which allow a Ca2+ influx. In turn, this [Ca2+]i increase leads to an activation of the Ca(2+)-activated K+ channels at the basolateral membrane of OHCs which results finally in a reversible hyperpolarization of OHCs by K+ efflux. PMID- 8348314 TI - Time course of fiber outgrowth from fetal anterior hypothalamic heterografts. AB - Fetal anterior hypothalamic (AH) heterografts can restore circadian rhythmicity to animals rendered arrhythmic following ablation of the suprachiasmatic nucleus (SCN). Behavioral restoration of circadian activity typically begins between two and six weeks post-implantation. The time course of fiber outgrowth from fetal AH heterografts was examined to determine whether neuronal outgrowth from the implants precedes the typically observed effects of such implants upon circadian behavior. Fetal mouse or rat AH tissue containing the SCN was implanted into the third ventricle of SCN-lesioned hamsters. Using species-specific monoclonal antibodies generated against mouse or rat neuronal elements, fiber outgrowth into the host hypothalamus was examined at 2, 4, 7, 14, 30 and 45 days after implantation. Fibers were observed to have emerged from the implant at the earliest time point examined. Four days after surgery, individual fibers had extended up to 0.6 mm into the host neuropil. By 14 days post-implantation, outgrowth from the implant had formed a dense fiber plexus in the host hypothalamus. This observation demonstrates that neuronal integration of the implant with the host brain begins within 48 hours of implantation, and is extensively established well before a restoration of rhythmicity is typically observed. Thus, on the basis of the time course of fiber outgrowth, it is clear that neuronal contact between graft and host may mediate the observed restoration of circadian rhythmicity. PMID- 8348315 TI - The dorsal hippocampus modifies the negative feedback effect of glucocorticoids on the adrenocortical and median eminence CRF-41 responses to photic stimulation. AB - In the present study we have evaluated the role of the dorsal hippocampus on the negative feedback effect of glucocorticoids (GC) following photic stimulation. In hippocampectomized rats the recovery of serum corticosterone (CS) to basal levels following photic stimulation, was significantly attenuated in relation to sham hippocampectomized rats. The inhibitory effect of either systemic dexamethasone administration or CS implanted in the paraventricular nucleus (PVN), on the adrenocortical responses to photic stimulation, was completely prevented in hippocampectomized rats in comparison to sham operated animals. In rats with sham operation, the depletion of median eminence CRF-41 induced by photic stimulation, was prevented by pretreatment with CS PVN implants or systemic dexamethasone. These effects were reversed in rats with dorsal hippocampectomy. The results suggest that the dorsal hippocampus modulates the negative feedback of GC on the adrenocortical response following photic stimulation at the PVN level and this effect is mediated by median eminence CRF-41. PMID- 8348316 TI - Delayed detyrosination of alpha-tubulin from parallel fibre axons and its correlation with impaired synaptogenesis in hypothyroid rat cerebellum. AB - The biochemical basis of retarded differentiation and maturation of microtubules and impaired synaptogenesis in hypothyroidism has been investigated by studying the temporal and spatial relationship between alpha-tubulin detyrosination in the parallel fibre axons of rat cerebellum and alterations in the activity of the detyrosinating enzyme, TTCP (tubulinyl tyrosine carboxypeptidase) with the progress of synaptogenesis in the molecular layer. Detyrosination was monitored by following the disappearance of stain from cerebellar sections, immunocytochemically labeled with a monoclonal antibody (20C6) specific for alpha tubulin, tyrosinated at the C-terminal end. With respect to normal controls, detyrosination of alpha-tubulin from the parallel fibres of the molecular layer during synaptogenesis was not only delayed by about 5 days but also prolonged in the hypothyroid cerebellum. Correspondingly, the increase of TTCP activity in the developing thyroid deficient cerebellum was also delayed by about 1 week. Comparison of the developmental profile of TTCP activity in the normal and hypothyroid cerebellum during synaptogenesis revealed that the overall activity of the enzyme in the thyroid deficient cerebellum was reduced to almost half of that of the normal controls. These results establish that thyroid hormones are essential for the induction of TTCP, which catalyses detyrosination during the normal ontogenic development of rat cerebellum. Since our data also suggest that detyrosination precedes synaptic contacts to generate a class of differentiated microtubules functionally competent for synaptogenesis, the delayed detyrosination in the hypothyroid cerebellum may desynchronize the normal developmental program resulting in incomplete synaptogenesis. PMID- 8348317 TI - Extracellular gamma-aminobutyric acid levels in the rat caudate-putamen: monitoring the neuronal and glial contribution by intracerebral microdialysis. AB - Intracerebral microdialysis with high pressure liquid chromatography (HPLC) coupled to electrochemical detection was employed to characterize gamma aminobutyric acid (GABA) release and the effects induced by a preceding neuron depleting ibotenic acid (IBO) lesion in the rat caudate-putamen (CPu). Extracellular GABA overflow was monitored in the intact and excitotoxically lesioned CPu, either 7-10 days (acute) or more than 3 months post-lesioning (chronic), using loop type dialysis probes perfused at a rate of 2 microliters/min. In the intact CPuu, basal GABA levels were 0.97 pmol/30 microliters of dialysate in the awake animals and 0.76 pmol/30 microliters under halothane anaesthesia. In both the acute and chronic IBO lesioned CPu the extracellular GABA levels were reduced by 80% and 67%, respectively, under halothane anaesthesia. KCl added to the perfusion fluid at a concentration of 100 mM resulted in dramatic increases in GABA overflow from baseline levels in the intact CPu (60- to 70-fold), which were almost totally abolished (> 95%) in the excitotoxically lesioned CPu. Veratridine administered at 75 microM, produced a 45-fold increase in GABA overflow in the intact CPu, but failed to produce any effect in the lesioned CPu. The addition of nipecotic acid (0.5 mM), a GABA uptake blocker, increased basal extracellular GABA levels 6-15-fold in the intact CPu, while GABA overflow in either the acute or chronic lesioned CPu was not significantly altered. Although Ca(2+)-free conditions (with 20 mM Mg2+ added) or tetrodotoxin (TTX, 1 microM) did not alter the basal GABA overflow in the intact CPU under halothane anaesthesia, the omission of Ca2+ resulted in a 47% reduction in basal extracellular GABA levels in awake, freely moving animals. Nipecotic acid-induced GABA overflow was reduced by 22% under Ca(2+)-free conditions, and by 33% in the presence of 1 microM TTX. Moreover, KCl-evoked GABA overflow was reduced by 86% in Ca(2+)-free conditions and by 40% when administered in the presence of 1 microM TTX. These results indicate that the extracellular GABA levels recorded by intracerebral microdialysis in the CPu are derived predominantly from neuronal sources. Under baseline resting conditions only a small fraction (up to 20-30%) of the neuronal release was Ca(2+)-dependent and TTX-sensitive (i.e. possessing the characteristics of impulse-dependent vesicular release).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8348318 TI - Induced resistance and susceptibility to cerebral ischemia in gerbil hippocampal neurons by prolonged but mild hypoperfusion. AB - Brief periods of non-lethal cerebral ischemia can induce resistance against subsequent lethal ischemia. In this study, asymptomatic gerbils after unilateral carotid artery ligation were subjected to 5 min of forebrain ischemia. The prolonged but mild hypoperfusion, by carotid occlusion, induced susceptibility at 1 day and tolerance at 30 days to lethal ischemia in the hippocampal neurons. The neuroprotective effect correlated well with induction of heat shock protein 72 in the hippocampal neurons. These results suggested that neuronal cells possess a cellular response to sublethal hypoperfusion and can survive forthcoming ischemic stress. PMID- 8348319 TI - Responses of neurons in thalamic ventrobasal complex of rats to graded distension of uterus and vagina and to uterine suprafusion with bradykinin and prostaglandin F2 alpha. AB - This study examined the responses of somatic-responsive neurons in and near the ventrobasal complex (VB) of halothane/nitrous oxide-anesthetized and paralyzed estrous virgin rats to increasing levels of distension of the uterine horn and vaginal canal and to uterine suprafusion with PGF2 alpha and bradykinin (BK). While individual responses of single neurons to uterine and vaginal distensions were idiosyncratic, as a group the neurons responded in a graded fashion to graded distensions, producing stimulus-responses functions nearly identical to those produced by conscious rats making escape responses to the same stimuli [Berkley and Wood, Soc. Neurosci, Abstr., 15 (1989) 979; Berkley et al., Soc. Neurosci. Abstr., 16 (1990) 416]. In addition, most neurons responded vigorously to PGF2 alpha and BK, with responses to BK but not PGF2 alpha, reliably preceding the 'giant' uterine contractions that were also produced by these algogenic agents. These results indicate that certain neurons in and near VB may as a group be involved in some aspect of pain arising from female reproductive organs. The responses of these neurons to somatic and possibly other visceral stimuli, however, point to their potential additional involvement in other aspects of visceral and somatic nociception. PMID- 8348320 TI - Traumatic brain injury produces impairments in long-term and recent memory. AB - Traumatic brain injury (TBI) in humans typically produces neurological suppression and a longer lasting impairment of memory clinically defined as post traumatic amnesia. An animal model that reliably reproduces the physiological changes associated with TBI was used to assess the memory deficits following brain injury. Prior to TBI, rats were trained to perform one of four tasks that assessed either motor performance, long-term or recent memory. Rats were randomly assigned to one of three groups (anesthesia only, sham operation or fluid percussion). Following fluid percussion, used to produce TBI, rats were tested for 6 test sessions. The first session occurred 1-2 min after the experimental manipulation. The next 5 sessions followed the training schedule maintained prior to experimental manipulation. Differences in long-term memory occurred only in the first post-operative test session. Differences in recent memory performance were found across all 6 test sessions. The memory deficits were clearly dissociated from motor deficits. The similar memory deficits observed following human head injury and the experimentally produced TBI injury demonstrate that fluid percussion is a useful approach to examine underlying neurobiological mechanisms involved in head injury and possible clinical interventions. PMID- 8348321 TI - A subpopulation of large calbindin-like immunopositive neurones is present in the hippocampal formation in food-storing but not in non-storing species of bird. AB - The avian hippocampal formation (HP) is thought to play a role in the processing of spatial memory related to food-storing behaviour. The HP of two food-storing species (marsh tit (Parus palustris) and magpie (Pica pica)) and two non-storing species (great tit (Parus major) and jackdaw (Corvus monedula)) were compared following calbindin-like immunostaining. In the dorsal hippocampal region, both species of food-storing birds had larger calbindin-immunoreactive cells than did the two non-storing species. The fact that this association between storing behaviour and cell morphology is seen in two unrelated families of birds, the Paridae (marsh tit versus great tit) and Corvidae (magpie versus jackdaw) suggests that there may be a direct link between food-storing behaviour and the dorsal hippocampal calbindin-immunoreactive cell population. PMID- 8348322 TI - Morphine-evoked release of adenosine from the spinal cord occurs via a nucleoside carrier with differential sensitivity to dipyridamole and nitrobenzylthioinosine. AB - We have investigated the potential role of a bi-directional nucleoside carrier in the release of endogenous adenosine from spinal cord synaptosomes by examining the effects of dipyridamole and nitrobenzylthioinosine (NBI) on evoked release of adenosine. When 40 pmol adenosine were added to synaptosomes, only 70 +/- 2% was recovered, suggesting 30% uptake of adenosine. Dipyridamole (0.1-10 microM) reduced this uptake and also increased basal adenosine release, probably due to inhibition of the re-uptake of adenosine derived from released nucleotide. In contrast, NBI (0.1-10 microM) had no effect on either uptake of added adenosine or on basal release of adenosine. Addition of K+ (24 mM) and morphine (10 microM) produced a 50-60% increase in the release of adenosine, and this was reduced 35 98% by both dipyridamole and NBI (0.01-10 microM). Dipyridamole (0.01-1 microM) had no effect on the release of nucleotides (detected as adenosine) induced by noradrenaline, 5-hydroxytryptamine (5-HT) and capsaicin (50 microM each), although 10 microM dipyridamole significantly reduced release evoked by noradrenaline and 5-HT. This latter effect of dipyridamole was determined not to be due to inhibition of ATP release when measured directly. Within the spinal cord, there is a removal system for adenosine which is dipyridamole-sensitive but NBI-insensitive. Release of adenosine, but not nucleotides, appears to occur via this carrier system. The inhibition of release by NBI, but its lack of effect on uptake, suggests the involvement of heterogeneous carrier molecules in adenosine uptake and release from the spinal cord. PMID- 8348323 TI - Cl-/HCO3- exchange function differs in adult and fetal rat hippocampal neurons. AB - We studied Cl-/HCO3- exchange function in acutely dissociated single hippocampal neurons from adult and fetal day 18 rat using a fluorescent intracellular pH (pHi) indicator dye. The presence of Cl-/HCO3- exchange activity was assayed by observing the elevation in pHi upon acute reversal of the Cl- gradient. Resting intracellular pH in acutely dissociated neurons of both adult and fetal tissue was significantly higher than that of cultured fetal hippocampal neurons (day 10 12 in culture). Acute removal of extracellular Cl- caused a rapid and reversible increase in pHi by 0.25 pH units in adult neurons but had virtually no effect in similarly dissociated fetal neurons. Cl-/HCO3- exchange activity was also undetectable in fetal cultured hippocampal neurons. The mRNA for the anion exchanger AE3 is expressed abundantly in adult rodent neurons. AE3 is a potential candidate molecule for the observed Cl-/HCO3- exchange activity. In situ hybridization was used to monitor expression of the AE3 gene in these two age groups. We found that both adult and fetal neurons express AE3 mRNA. These results indicate that AE3 may not function as a Cl-/HCO3- exchanger in fetal neurons, in contrast to its possible role in the adult brain. PMID- 8348324 TI - Effect of ibuprofen on regional eicosanoid production and neuronal injury after forebrain ischemia in rats. AB - Post-ischemic metabolism of arachidonic acid by cyclooxygenase results in the elaboration of numerous eicosanoids and in the generation of free radicals. Accordingly, the effect of cyclooxygenase inhibition by ibuprofen on post ischemic eicosanoid production and delayed neuronal death was evaluated in Wistar Kyoto rats subjected to incomplete forebrain ischemia. In control (C) and ibuprofen-treated groups (n = 5 each), pre- and post-ischemic eicosanoid production in the caudate nucleus (CN) and dorsal hippocampus (HPC) were evaluated by microdialysis. The ibuprofen-treated animals were given ibuprofen, 15 mg/kg i.v., prior to insertion of microdialysis probes. Forebrain ischemia was induced by bilateral carotid artery occlusion (BCAO) for 10 min with simultaneous hypotension to 35 Torr. The concentrations of thromboxane B2 (TxB2), 6-keto-PGF1 alpha and PGF2 alpha in the microdialysate were measured by radioimmunoassay. In two additional concurrent groups of rats (n = 10 each), neuronal injury in the HPC, CN and cortex (parietal, temporal and entorhinal regions) was evaluated histologically three days after 10 min of forebrain ischemia with and without pre ischemic ibuprofen administration. In the control microdialysis group, levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha increased in both CN and HPC after probe insertion. These probe related increases were substantially reduced in the ibuprofen group. After ischemia and reperfusion in the control group, the levels of TxB2 and PGF2 alpha increased in both CN and HPC. Levels of 6-keto-PGF1 alpha increased in the CN but not in the HPC. The administration of ibuprofen substantially reduced post-ischemic TxB2 and PGF2 alpha levels in both CN and HPC and decreased 6-keto-PGF1 alpha levels in the CN. The results of these initial microdialysis studies left the possibility that, in the ibuprofen group, the reduction in eicosanoid levels after probe penetration might have influenced the subsequent post-ischemic eicosanoid production. Therefore, in an additional group of animals (n = 5), ibuprofen was administered after probe insertion. Only PGF2 alpha levels were measured in this group. Increased levels of PGF2 alpha comparable to the original control group were detected after probe penetration. Nonetheless, after ibuprofen administration, the pre- and post-ischemic levels of PGF2 alpha were again significantly reduced. In the histologic evaluation groups, overall neuronal injury was significantly less in the ibuprofen treated animals. This protective effect of ibuprofen was most clearly evident in the CA3 sector of the HPC.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8348325 TI - Down-regulation of phosphatidylinositol response to BDNF and NT-3 in cultures of cortical neurons. AB - The hydrolysis of phosphatidyl 4,5-bisphosphate (PI), which is involved in the transduction mechanism of neurotransmitters and growth factors, is stimulated by brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in primary cultures of fetal brain neurons. In the present study we sought to examine the effect of pretreatment with these factors on their acute stimulation capabilities and, furthermore, to substantiate that the effects of BDNF and NT-3 reflect actions on neurons rather than glial cells. Pretreatment with BNDF and NT-3 for 4 days followed by 1 day without growth factor abolished the effect of an acute stimulation with these factors. The growth factors were mutually effective so that BDNF pretreatment abolished the acute response to NT-3 and vice versa. In contrast, the effects of bFGF (basic fibroblast growth factor, a non-neurotrophin growth factor) also stimulating PI hydrolysis in these culture systems, were not reduced by neurotrophin pretreatment. Pretreatment with K-252b, at concentrations known to inhibit trk receptors, did not alter the acute stimulation of PI hydrolysis induced by the neutrophins. PI hydrolysis stimulated by BDNF and NT-3 in cultures grown in presence of cytosine arabinoside C, containing > 95% neurons, was higher than in cultures containing non-neuronal cells, indicating that the neurotrophin stimulation occurs in neuronal cells. No stimulatory effect was detected in bFGF treated pure neuronal cultures. The findings suggest that prolonged exposure of responsive neurons to BDNF and NT-3 down-regulates their stimulatory effects on PI hydrolysis. PMID- 8348326 TI - Chronic exposure to environmental levels of lead impairs in vivo induction of long-term potentiation in rat hippocampal dentate. AB - This study examined the effects of chronic developmental lead (Pb) exposure in rats on hippocampal long-term potentiation (LTP). Male offspring were exposed to 0.2% Pb acetate continuously from birth until testing at 85-105 days. Excitatory postsynaptic potential (EPSP) and population spike amplitudes were measured in the dentate hilar region in response to stimulation applied to the lateral perforant path. LTP was induced in control animals with an average maximal EPSP potentiation of 41%, which was significantly greater than the increase in EPSP amplitudes (2%) in exposed animals after tetanizing stimulation. Current-voltage curves in controls demonstrated significant increases in EPSPs and population spikes after application of pulse trains to induce LTP, while exposed rats exhibited no discernible change in responses. These findings suggest that induction or development of LTP in the dentate hilar region in vivo is impaired by chronic developmental exposure to environmentally relevant levels of Pb. PMID- 8348327 TI - Short periods of hypoxia activate a K+ current in central neurons. AB - The effect of hypoxia on ionic currents was studied in acutely dissociated substantia nigra neurons. Using an external solution containing 0 mM Na+ and 0.5 mM Co2+, we found that overall whole-cell outward currents increased by 15-20% during 3-4 min of hypoxia. This current was voltage sensitive and could be completely blocked by TEA- and Cs+, suggesting that this is a K+ current. In cell attached patches with 150 mM K+ in the external solution, we recorded a large conductance outward current which was not observed during baseline and was reversibly activated by hypoxia. These results therefore provide the first direct evidence for the activation of K+ channels during O2 deprivation in central neurons. PMID- 8348328 TI - 5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala. AB - The density (Bmax) of 5-HT2 receptors labelled with [3H]ketanserin was significantly increased in prefrontal cortex (by 67%) and amygdala (by 97%) from suicide/depressives in comparison with controls. There were no differences in Kd of [3H]ketanserin binding between the two groups. The density (Bmax) and affinity (Kd) of [3H]paroxetine sites were not significantly different in the suicide/depressives and controls. The ratio between the density of presynaptic 5 HT uptake sites and postsynaptic 5-HT2 receptors in amygdala was significantly lower in suicide/depressives than in controls. The data confirm and extend some of the previous findings of increases in 5-HT2 receptors in post-mortem brains of suicide victims and depressives who died of natural causes and lend support to the view that an abnormality in brain serotonergic system is associated with depression and suicidal behaviour. PMID- 8348329 TI - Self-sustained spreading depressions in the chicken retina and short-term neuronal-glial interactions within the gray matter neuropil. AB - The chicken retina is an accessible piece of intact gray matter in which a self sustained form of the 'Spreading Depression' (SD) wave can be easily elicited and recorded for many hours with double barrel ion-sensitive electrodes in the extracellular space. The blockade of glial (Muller) cell potassium channels with barium chloride added to the perfusing Ringer depressed both the negative potential shift typical of SDs and the velocity of spread. Moreover, there was separation of the extracellular increase of potassium and the drop in the extracellular potential: the peak of the potassium wave was increased, as well as its duration whereas the potential wave could be depressed to zero or even inverted to positive. By contrast the transient extracellular calcium drop could not be separated from the extracellular potential wave but appeared related to it: no transient calcium drop was observed when the negative potential was completely depressed or inverted. Both, the amplitude of the extracellular potential and extracellular calcium activity appeared to be important factors controlling the velocity of spread. PMID- 8348330 TI - Strain-dependent differences in responsiveness of mice to nitrous oxide (N2O) antinociception. AB - N2O antinociception was assessed in eight inbred and two outbred mouse strains. Results indicated the following order of responsiveness among the 10 strains: A/J (most sensitive), C57BL/6ByJ, C57BL/6J, BALB/cByJ, C3H/HeJ, Swiss-Webster, CXBK/ByJ, ICR, CBA/J and DBA/2J (least sensitive). These results demonstrate significant strain-dependent differences in antinociceptive responsiveness to N2O. The weak antinociceptive response to N2O in the DBA/2J strain, which is sensitive to morphine and U-50, 488H, indicates some underlying neurobiological difference in the DBA/2J mouse that imparts resistance to N2O. The responsiveness of CXBK/ByJ mice to N2O indicates that mu-opioid receptors may not play an important role in N2O antinociception in mice. PMID- 8348331 TI - Radioimmunoligand characterization and immunohistochemical localization of dopamine D2 receptors on rods in the rat retina. AB - The retinal neurotransmitter dopamine (DA), elaborated from intrinsic dopaminergic neurons as amacrine and interplexiform cells, is known to modulate several complex functions mediated by D1 and D2 receptors in the vertebrate retina. In this paper, we characterized and localized DA receptors of the D2 family on rod outer segments (ROS) of the rat retina by a radioimmunoligand binding assay and by immunohistochemistry. Anti-anti-DA conjugated antibodies (or anti-idiotypic antibodies Ab2) were used as ligand; BSA-glutaraldehyde-conjugated spiperone, eticlopride (D2 antagonists) and DA were used as displacers. The linear Scatchard transformation indicated that data were best fit to the one-site model. By using the peroxidase-antiperoxidase technique, an intense labeling was located on rods. These results supported the paracrine action of DA on the photoreceptor cell. PMID- 8348333 TI - Hormonal and metabolic effects of neuroglucopenia. AB - We examined the role of central neuroglucopenia, induced by intracerebroventricular (i.c.v.) administration of 2-deoxyglucose (2-DG), on glucose and amino acid kinetics in conscious dogs. Group 1 received i.c.v. 2-DG at 2.5 mg.kg-1 x min-1 for 15 min. Group 2 received an equal intravenous (i.v.) amount of 2-DG. In the i.c.v. group, plasma glucose levels rose from 106 +/- 4 mg/dl to a peak of 204 +/- 12 mg/dl by 90 min. Blood lactate increased from 689 +/- 1 to 2,812 +/- 5 mumol/l and blood alanine not change from basal (256 +/- 41 mumol/l). The rate of hepatic glucose production, determined isotopically, was increased 2-fold over basal (P < 0.01). Significant increases (P < 0.001) over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon and cortisol. Leucine rate of appearance (Ra) showed a 30% decrease from basal to 2.4 +/- 0.05 mumol.kg-1 x min-1 (P < 0.01). In group 2 plasma glucose levels were not altered but plasma cortisol and glucagon showed a modest transient increase above basal (P < 0.05). No significant changes were noted in amino acid kinetics. These findings suggest that periventricular neuroglucopenia, in the absence of peripheral glucose deprivation, is accompanied by hyperglycemia secondary to enhanced hepatic glucose production with decreased glucose utilization and by increased hepatic uptake of gluconeogenic precursors. These, however, were not accompanied by increased whole body proteolysis as was previously seen with generalized glucopenia resulting from insulin-induced hypoglycemia. PMID- 8348332 TI - Mating activates androgen receptor-containing neurons in chemosensory pathways of the male Syrian hamster brain. AB - Fos-immunoreactivity is induced during mating in the male Syrian hamster in limbic areas that relay chemosensory information and contain receptors for gonadal steroid hormones. The induction of Fos is an index of neuronal activation. After mating, c-fos expression is greatest in subnuclei of the medial amygdaloid nucleus (Me), bed nucleus of the stria terminalis (BNST), and medial preoptic area (MPOA). The present study determined if individual neurons in these activated subnuclei contain androgen receptors. We aim to understand how essential chemosensory and hormonal signals are integrated to control copulation. Adult male hamsters (n = 6) were allowed to mate with a sexually receptive female for 30 min. They were perfused 1 h later with 4% paraformaldehyde and 40 microns frozen sections were processed for immunocytochemistry using antisera against Fos (Cambridge Research Biochemicals) and the androgen receptor (G.S. Prins). The brains of three non-mated males were also processed for Fos immunocytochemistry. Mating significantly increased the number of Fos-immunoreactive neurons within subnuclei of Me, BNST, and MPOA relative to non-mated males (P < 0.05). These nuclei contained abundant androgen receptors. In the corticomedial amygdala, 20 40% of Fos-immunoreactive neurons in mated hamsters expressed androgen receptors. Although few androgen receptors are found in the anteromedial and postero intermediate subdivisions of the BNST, these areas exhibited 26% and 47% co localization, respectively. In posteromedial BNST, which contains large numbers of steroid receptor-containing neurons, androgen receptors were identified in 48% of Fos-immunoreactive neurons. In the MPOA, 54% of Fos-immunoreactive neurons expressed the androgen receptor throughout the rostrocaudal extent of the medial preoptic nucleus (MPN).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348335 TI - Paired-pulse and frequency potentiation of cortical responses in developing rats. AB - The postnatal development of paired-pulse and frequency potentiations of the first positive and negative components (P1N1) of the cortical interhemispheric response (IHR) was studied in urethane anesthetized rats aged from 7 to 90 days. The paired-pulse potentiation appeared in the rat sensorimotor cortex starting from the age of 15 days. The magnitude of potentiation increased with age. The interpulse interval inducing maximum potentiation shortened from 125 ms in 15-day old rats to 70 ms in adult rats. Similar results concerning the paired-pulse responses were found for visual cortex but the maturation was somewhat delayed- potentiation first appeared at postnatal day (PND) 18. The frequency potentiation reached adult properties in the sensorimotor cortex by PND 25. There is no time coincidence in the development of the two potentiation phenomena studied, paired pulse potentiation appeared earlier than frequency potentiation. PMID- 8348334 TI - Effect of Pinellia ternata tuber on the efferent activity of the gastric vagus nerve in the rat. AB - Effect of intraduodenal infusion with the hot aqueous extract of Pinellia ternata tuber on the efferent discharges in the gastric branch of the vagus nerve was observed in the anesthetized rat. The infusion of the extract in doses of 2-15O mg per animal (c.a. 300 g, b.wt.) resulted in a dose-related increase in efferent activity of the vagal gastric nerve. The enhancement of the nerve activity following administration of 150 mg of this substance lasted longer than 90 min. It was observed that the suppressive effect on vagal gastric activity due to apomorphine and copper sulfate was antagonized by prior administration of the extract. From these observations it is suggested that Pinellia tuber acts as a facilitatory agent on gastric function. PMID- 8348336 TI - Stimulation-induced RSA-like field activity in region CA1 of the hippocampal slice: amplitude maxima and topography. AB - In the present experiment RSA-patterned stimulation was applied to afferents in the CA1 region of the hippocampal slice preparation and depth profiles of the resultant field activity were performed. RSA-patterned stimulation applied to the stratum lacunosum-moleculare region resulted in field activity through the CA1 region with similar morphology, phase, and amplitude profiles to the type 1 RSA profile found in vivo. In contrast, RSA-patterned stimulation applied to the stratum oriens and midstratum radiatum regions did not result in field profiles characteristic of the RSA recorded in vivo. The results of the present study confirm predictions made by previous modelling experiments and CSD analyses performed in the freely moving animal, which suggest that the type 1 RSA profile is primarily the result of distal excitation onto CA1 pyramidal cells. PMID- 8348338 TI - Differential effects of NE, CLON, and 5-HT on feeding and macronutrient selection in genetically obese (ob/ob) and lean mice. AB - The effects of central injection of norepinephrine (NE), clonidine (CLON), and 5 hydroxytryptamine (5-HT) on feeding and macronutrient selection in genetically obese (C57B1/6J, ob/ob) and lean mice (C57B1/6J, +/?) were examined. Mice were adapted to single-energy source diets of carbohydrate, protein, and fat and then injected with NE (20-80 nmol) or CLON (5-20 nmol) immediately prior to dark onset (17h00). Measurements of nutrient intake were determined 2 h postinjection. In a separate study, obese and lean mice were deprived of food for 1 h (1700-1800) and subsequently treated with 5-HT (35-140 nmol). The results of this study demonstrate that the hyperphagic effect of NE and CLON and the anorectic effect of 5-HT are dose dependent and nutrient selective. Specifically, at the onset of the nocturnal cycle, obese and lean mice exhibit a shift in diet choice resulting in an increased preference for carbohydrate and a reduction in the proportional intake of protein and fat. At this time, central injection of NE or CLON potentiates an already enhanced preference for carbohydrate; whereas injection of 5-HT suppresses carbohydrate intake (kcal) in both phenotypes without altering fat or protein intake. However, in comparison to lean mice, obese mice showed significantly augmented hyperphagic responses to NE and CLON administration but decreased inhibition of feeding after 5-HT injection. This suggests that the stimulatory effect of alpha 2-noradrenergic mechanisms controlling feeding and carbohydrate ingestion is enhanced in obese mice, while the inhibitory influence of serotonergic mechanisms is attenuated. PMID- 8348337 TI - Aromatic amino acid decarboxylase (AADC) immunohistochemistry in vertebrate brainstem with an antiserum raised against AADC made in E. coli. AB - Aromatic L-amino acid decarboxylase (AADC) is involved in the biosynthesis of catecholamines and indolamines. AADC is present in the nervous system, in the chromaffin cells, and in non-neuronal tissues. We tested the capacity of a new polyclonal antibody, obtained by immunization of rabbits with a recombinant protein beta-galactosidase-AADC, to detect monoaminergic neurons in the brainstem as well as monoaminergic paraneurons in the adrenal medulla from goldfish, frog, skink, quail, and mouse. In the adrenal gland we found an immunoreactivity that was consistent with the distributions of the chromaffin cells previously reported. In the brainstem, groups of immunoreactive neurons and several labelled fibers were observed in the five species studied. The raphe region showed cell bodies and processes similar to those previously identified as monoaminergic by other authors. In addition, in medulla oblongata and isthmic tegmentum we found, in goldfish, skink, and quail, neuronal groups similar to mammalian D groups which contain AADC but are devoided of serotonin and catecholamines. PMID- 8348339 TI - Sleep-inducing function of noradrenergic fibers in the medial preoptic area. AB - The aim of the investigation was to find out the role of noradrenergic (NE) terminals of the medial preoptic area (mPOA), in the regulation of sleep wakefulness. Studies were conducted on free-moving adult male rats with chronically implanted cannulae in the mPOA. Sleep-wakefulness was assessed on the basis of EEG, EMG, and EOG recordings along with behavioral observations. Lesioning of catecholamine terminals (with 6-hydroxydopamine) in the mPOA produced an increase in quiet wakefulness. Prevention of NE fiber destruction, by pretreating the rats with imipramine, prevented this effect. This demonstrated that the increased quiet wakefulness produced by 6-OHDA was the result of NE fiber destruction. Changes in sleep-wakefulness were also assessed after microinjection of NE into the mPOA, in normal and ventral noradrenergic bundle (VNA)-lesioned rats. NE administration induced sleep in VNA-lesioned rats, and arousal in normal rats. The findings suggest that the NE terminals in the mPOA, projecting via VNA, play a role in the induction of sleep. PMID- 8348340 TI - Development of monoamine systems after neonatal anoxia in rats. AB - Neurochemical and morphological effects of neonatal anoxia on monoamine systems were studied after 100% N2 exposure for 25 min at 30 h postnatally (postnatal day 2-P2). At 20 min after anoxia, reductions of tissue levels of cerebellar noradrenaline (NA) and striatal dopamine (DA) and metabolites were seen, while 5 hydroxyindoleacetic acid (5-HIAA) was increased in cortex and cerebellum. At P7, NA increased in cerebellum, while serotonin (5-HT) and 5-HIAA decreased in cortex and cerebellum. At P21, increased hippocampal NA and striatal homovanillic acid (HVA) were found, while striatal 5-HT decreased and 5-HIAA increased in striatum and hippocampus. At P60, striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and 5 HIAA levels were found to be enhanced. No effects were seen on 5-HT, tyrosine hydroxylase, or DARPP-32 immunostaining in cortex, hippocampus, and striatum. Thus, the neonatal anoxia induced both acute and persistent neurochemical abnormalities in monoamine systems that were not accompanied by morphological changes detectable with the methods used. The monoamine alterations found could be critically connected to the behavioral disturbances observed in rats after neonatal anoxia. The findings may also be of relevance to dysfunctions seen in humans after perinatal oxygen deficiency, e.g., the attention deficit hyperactivity disorder syndrome. PMID- 8348341 TI - Hippocampal and entorhinal glucose metabolism in relation to cholinergic theta rhythm. AB - Hippocampal and entorhinal cortex glucose metabolism were studied by 14C-2 deoxyglucose (2-DG) autoradiography in anesthetized rats with and without continuous theta rhythm (theta). 2-Deoxyglucose changes in specific cytoarchitectonic regions were precisely assessed by n innovative approach. In the absence of theta there were areas with a higher glucose metabolism corresponding to neuropile regions at CA3, dentate gyrus, and subiculum, while the cellular layers always showed lower values. In the presence of theta, provoked by intraventricular injections of anticholinesterases (i.e., physostigmine) or curarimimetics (i.e., d-tubocurarine), 2-DG uptake showed two opposite significant changes in relation to controls: a) it increased in the outer zone of the molecular layer (inner blade) of the dentate gyrus, and in the stratum lacunosum-moleculare of CA3, suggesting an increase in perforant path input during theta rhythm; b) it decreased in the hilar dentate region. This noteworthy decrease in metabolic activity probably reflects an hilar inhibition by local circuits during theta rhythm generation. PMID- 8348342 TI - Effect of systemic morphine on neurons in the lateral reticular nucleus area of the rat. AB - The present study is undertaken to investigate the effect of systemic morphine on neurons in the lateral reticular nucleus (LRN) using extracellular recording techniques. The spontaneous activities of 64 neurons in the LRN area were tested with morphine (3-5 mg/kg, IV). Morphine excited 23 and inhibited 28 neurons tested, and 13 neurons were not affected. Of the 28 neurons inhibited, 20 were identified as nociceptive and the remaining 6 were nonnociceptive. Of the 23 neurons excited by morphine, 18 were nociceptive and 5 were nonociceptive. Systemic naloxone (0.3-0.5 mg/kg) significantly reversed the morphine effect in 15 out of 19 neurons excited and 19 out of 20 neurons inhibited by morphine. Thirteen out of 64 neurons were further identified as reticulospinal neurons, of which four were excited and four were inhibited by morphine. The remaining five were not affected. The results demonstrate that a similar proportion of neurons in the LRN area were either excited or inhibited by systemic morphine, and the majority of them are nociceptive neurons. It is suggested that different types of neurons in the LRN area may have different functions in morphine analgesia. PMID- 8348343 TI - A sex comparison of serotonin immunoreactivity and content in the ferret preoptic area/anterior hypothalamus. AB - Previous studies with rats raised the possibility that sexually dimorphic features of the medial preoptic area/anterior hypothalamus (POA/AH) may result, in part, from a sex difference in the serotonergic innervation of this region. We asked whether a similar phenomenon may occur in a carnivore, the ferret. A sexually dimorphic male nucleus of the dorsal POA/AH (Mn-POA/AH) has previously been characterized in Nissl-stained sections of the male ferret forebrain; this nucleus is absent in females. A nondimorphic ventral nucleus of the POA/AH is found in both sexes. In the present study numerous serotonin (5-HT) immunoreactive (ir) fibers were observed in the dorsal POA/AH of gonadectomized adult ferrets of both sexes. By contrast, in both sexes the ventral nucleus of the POA/AH had many fewer 5-HTir fibers. A similar difference in the distribution of immunoreactivity between dorsal and ventral POA/AH was observed for tyrosine hydroxylase (TH) localized in cell bodies and in nerve fibers and for H222ir estrogen receptors localized in cell nuclei. Likewise, in both sexes the content of 5-HT and dopamine (DA), measured by high pressure liquid chromatography with electrochemical detection, were significantly higher in the dorsal than the ventral POA/AH, thereby corroborating observed regional differences in 5-HTir and THir fibers, respectively. The present findings provide no support for the notion that sexually dimorphic cytoarchitectonic features of the dorsal POA/AH in ferrets are associated with a sex difference in the serotonergic innervation of this region. PMID- 8348344 TI - Improved yield of obese rats using a double coordinate system to locate the ventromedial or paraventricular nucleus. AB - This article describes a highly efficient method for making VMH and PVN-lesioned obese rats by using a newly developed coordinate system. In previous methods, the coordinates for creating VMH and PVN lesions were determined from single point, either the interaural line or the bregma. Because skull size varies, the use of two reference points resulted in greater consistency. We therefore developed a system for making VMH- and PVN-lesioned obese rats using both the interaural line and the bregma. With this new double coordinate system the success rate for producing obese rats varied from 52% to 92% for VMH lesions and from 36% to 61% for PVN lesions. PMID- 8348345 TI - Topographic organization of efferent projections of medial frontal cortex. AB - By using fluorescent retrograde tracers, we compared efferent projections of the medial frontal cortex to two subcortical areas: the superior colliculus, a somatic motor area, and the laterodorsal tegmental nucleus, a visceral motor area. Neurons projecting to the superior colliculus originated in layer V of the cingulate (Cg1 area) and medial agranular cortex, while neurons projecting to the laterodorsal tegmental nucleus originated in layers V and VI of the cingulate (Cg3 area) and infralimbic cortex. Thus, within the medial frontal cortex, the ventral portion (the Cg3 and infralimbic areas) may be a visceral motor area while the dorsal portion is a somatic motor region. PMID- 8348346 TI - A simple cannula assembly for chronic bilateral brain infusion in freely moving rats. AB - Osmotic minipumps provide a means for the chronic infusion of agents into the brain of the awake unrestrained animal. This paper describes the construction of a simple and inexpensive cannula assembly to be used with an osmotic minipump for the bilateral infusion of brain regions in the rat. The cannula/catheter assembly employs the use of a Y-joint, thereby allowing the investigator to use only one osmotic minipump per animal. This reduces the flow rate and decreases the cost of an experiment. Chronic infusion of the ventral septal area with saline using this system failed to alter the circadian rhythm of body temperature, except for a significant decrease in the amplitude of the rhythm. PMID- 8348347 TI - Effects of chronic desipramine administration on the locus coeruleus neuronal activity in the learned helplessness paradigm. AB - One week after inescapable shock (IS) exposure, animals showed an increased number of escape failures in the shuttlebox and a decreased noradrenergic (NA) transmission. The latter was assessed by electric activity of locus coeruleus (LC) neurons. Seven daily injections of desipramine (DMI) were effective in reducing the number of escapes failures in the shuttlebox, but such treatment did not modify the decreased electric activity of LC NA neurons observed 7 days after IS. These results are discussed in terms of the action of DMI on NA terminals in reversing the behavioral deficit induced by IS. PMID- 8348348 TI - Sex differences in salt preference and taste reactivity in rats. AB - Previous studies have shown that female rats consume significantly more sodium chloride (NaCl) than do age-matched males. The gustatory contribution to this sex difference was examined in the following experiments. In Experiment 1, female rats demonstrated a higher two-bottle preference for NaCl ranging from 0.03 M to 1.0 M than did age-matched males. Next, to determine if the animal's sex modified gustatory sensitivity for NaCl, taste reactivity responses elicited by intraoral infusions (0.8 ml) of NaCl (0.03 M, 0.15 M, 0.3 M, and 1.0 M) were measured in age-matched male and female Sprague-Dawley rats. Intraoral infusions of NaCl were administered in ascending concentration order on successive days. During the intraoral infusion, the animal's oral motor taste reactivity responses were videotaped and subsequently analyzed to determine the number of ingestive and aversive responses. Intraoral infusions of 0.15 M and 0.3 M NaCl elicited reliably more ingestive responses and 1.0 M NaCl more aversive responses in females than in males. Because differences in taste reactivity were not found for all those concentrations for which female rats showed a higher preference than did males, changes in gustatory sensitivity contributes to, but does not appear to fully account for the female rats' preference for NaCl. PMID- 8348349 TI - Standards of practice for diagnostic radiology. PMID- 8348350 TI - Stenosis of the carotid bifurcation: subjective assessment compared with strict measurement guidelines. AB - Preliminary results of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) have shown that endarterectomy is highly effective in preventing stroke in patients with 70% to 99% stenosis of the carotid bifurcation. These results are based on specific linear measurement criteria comparing the residual diameter of the lumen with that of the normal carotid beyond the bulb. These criteria may differ from subjective assessments of the severity of stenosis. Angiograms from 125 NASCET patients were analysed independently by three groups of reviewers. The first group consisted of three neuroradiologists, the second of two neurologists and one neurosurgeon and the third of three radiologists with neuroradiologic experience. The degree of stenosis was estimated, without measurement, as mild (1% to 29%), moderate (30% to 69%) or severe (70% to 99%), or the vessel was said to be occluded. These assessments were compared with the degree of stenosis as determined by the NASCET neuroradiologist on the basis of measurement. The subjective assessment of stenosis produced false-positive rates (for assessing stenosis of less than 70% as severe) ranging from 5% among the neuroradiologists to 16% among the radiologists. The false-negative rates (for assessing stenosis of 70% or more as less than severe) ranged from 12% to 22%. Therefore, a subjective rating of carotid stenosis may lead to erroneous estimation of the severity of disease. This problem has therapeutic implications, because carotid endarterectomy has been shown to benefit only patients with stenosis of greater than 70%, as assessed according to strict measurement guidelines. PMID- 8348351 TI - [Antegrade puncture of the superficial femoral artery: a pilot project]. AB - Antegrade puncture of the femoral artery is often the first step in angioplasty or thrombolysis of the lower limb. Because of presumed complications, mostly from anecdotal literature, the common femoral artery is the preferred site of entry. From there, selective catheterization of the superficial femoral artery can be performed. This two-step procedure is sometimes long and difficult for both the patient and the radiologist. To improve the ease and the rapidity of this procedure, the author performed direct antegrade puncture of the superficial femoral artery during 25 consecutive antegrade approaches. The only local complication was hematoma, which developed in two patients but disappeared spontaneously. Aggravating factors were the size of the catheters used and fibrinolytic therapy in one of the affected patients. The results of this pilot study suggest strongly that direct antegrade puncture of the superficial femoral artery is safer than might be expected from the literature, which deals primarily with retrograde puncture. This approach must now be systematically compared with the "classic" common femoral artery approach. PMID- 8348352 TI - Excimer-laser-assisted angioplasty in chronic femoropopliteal occlusion: the significance of an intimal flap in predicting reocclusion. AB - Angioplasty assisted by excimer laser was performed on 27 chronic femoropopliteal occlusions, ranging from 2 to 30 cm in length, in 26 patients. Twenty-one (78%) of the procedures were successful initially. Of these, 12 (57% [44% of the total]) remained patent at follow-up 3 months later. In seven of the nine cases of reocclusion observed after 3 months (78%) a large intimal flap resulting from the angioplasty-induced dissection could be identified in the postprocedure angiogram. The authors stress the possible importance of such an intimal flap in limiting the success of laser-assisted angioplasty of long femoropopliteal occlusions. PMID- 8348353 TI - Same-day computed tomography during arterial portography and delayed high-dose iodine computed tomography: an efficient approach to imaging potentially resectable liver tumours. AB - Preoperative imaging in patients with potentially resectable liver tumours has traditionally been performed in specialized hepatobiliary centres. To assess the feasibility and value of establishing a same-day, pre-resectional hepatic imaging service, computed tomography during arterial portography (CTAP) and delayed high dose iodine computed tomography (DICT) were used to examine patients considered suitable for curative hepatic resection. The study group comprised 27 patients (14 from hospitals not affiliated with a university and 13 from two university affiliated hospitals) for whom pre-referral imaging showed tumour distribution amenable to resection. Among the patients from centres not affiliated with a university, seven had undergone ultrasonography (US) and equilibrium-phase CT, four had undergone US and unenhanced CT, two had undergone equilibrium-phase CT only and one had undergone bolus dynamic incremented CT (BDCT) only. For 12 of the patients coming from the university-affiliated centres, the pre-referral imaging had consisted of US and BDCT; the other had undergone US only. After CTAP and DICT, 20 (74%) of the 27 patients were reclassified as having unresectable disease: 7 (54%) of the 13 patients who had undergone BDCT before CTAP and DICT and 12 (92%) of the 13 patients who had undergone unenhanced or equilibrium-phase CT, as well as the patient who had undergone US only. By averting laparotomy in 20 of the patients, CTAP and DICT resulted in short-term health care savings of about $160,000. These findings suggest that BDCT was underused in the hospitals not affiliated with university centres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348354 TI - A limited, low-dose computed tomography protocol to examine the sacroiliac joints. AB - Limited, low-dose, three-scan computed tomography (CT) was shown to be as accurate as a complete CT series in examining the sacroiliac joints and is suggested as an effective alternative to plain radiography as the primary means to detect sacroiliitis. The advantages include the brevity of the examination, a 2-fold to 4-fold reduction in radiation exposure relative to conventional radiography and a 20-fold to 30-fold reduction relative to a full CT series. The technique was developed from studies of anatomic specimens in which the articular surfaces were covered with a film of barium to show clearly the synovial surfaces and allow the choice of the most appropriate levels of section. From the anteroposterior scout view the following levels were defined: at the first sacral foramen, between the first and second sacral foramina and at the third sacral foramen. In the superior section a quarter of the sacroiliac joint is synovial, whereas in the inferior section the entire joint is synovial. The three representative cuts and the anteroposterior scout view are displayed on a single 14 x 17 in. (36 x 43 cm) film. Comparative images at various current strengths showed that at lower currents than conventionally used no diagnostic information was lost, despite a slight increase in noise. The referring physicians at the authors' institution prefer this protocol to the imaging routine previously used. PMID- 8348355 TI - Ossification of the hyoid bone during childhood. AB - Normal ossification of the hyoid bone was studied on the basis of postpartum radiographs of 10 stillborn children and radiographs of the cervical spine or the lateral neck of 86 children ranging in age from newborn to 16 years old. None of the patients was suspected of having any abnormality of skeletal ossification. Ossification of the hyoid was seen only after 30 weeks' gestation. The body of the hyoid was ossified in all infants older than 4 months, and the greater cornua were ossified in all those older than 6 months. Ossification of the lesser cornua did not appear in children less than 15 years of age. Normal measurements for the body of the hyoid and the greater cornua were determined. PMID- 8348356 TI - Abnormal ossification of the hyoid bone in cleidocranial dysplasia. AB - Radiographs of the hyoid region of 13 patients with cleidocranial dysplasia were reviewed. In all but one the hyoid bone was less ossified than normal. Delayed ossification, affecting the skull, the teeth, the pelvis and the extremities, is a known, frequent manifestation of this abnormality. PMID- 8348357 TI - Congenital absence of a pedicle in a cervical vertebra: report of two cases. AB - Two cases of congenital absence of a cervical vertebral pedicle are reported. This condition includes hypoplasia of the ipsilateral posterior arch and may predispose to spinal cord injury. The radiographic and computed tomography (CT) findings are reviewed, and the importance of the ipsilateral oblique radiographic view and of CT in diagnosis is stressed. PMID- 8348359 TI - Carpal instability in rheumatoid arthritis. AB - The authors examined prospectively the prevalence of and relations among patterns of carpal instability in 52 patients with proven rheumatoid arthritis. Posteroanterior, lateral and oblique radiographs of both wrists were obtained. Nineteen patients exhibited one or more patterns of instability. The most common isolated pattern was volar intercalated segmental instability, apparent in six patients. Five patients showed more than one pattern, most commonly a combination of ulnar translocation and volar carpal subluxation. Patients with active erosions or changes in the distal radioulnar joint were more likely to exhibit instability than those without such findings. Carpal instability is a frequent mechanical complication of rheumatoid arthritis. The radiologist should be aware of this possibility, so that a diagnosis can be made promptly and appropriate clinical management begun. PMID- 8348358 TI - Parosteal lipoma with hyperostosis: report of two pathologically proven cases evaluated by magnetic resonance imaging. AB - The authors describe two cases of parosteal lipoma, an infrequent benign tumour, associated with hyperostosis. The first patient presented with a mass in the posterior neck, the other with one in the proximal forearm. Radiologic diagnosis was facilitated by magnetic resonance imaging (MRI). The MRI images showed the characteristic features of a parosteal lipoma, as well as hyperostotic areas that remained of low signal intensity in both T1-weighted and T2-weighted sequences. MRI is both sensitive and specific for diagnosing these lesions and provides excellent depiction of the anatomic features before surgery. PMID- 8348360 TI - Injected silicone: radiologic appearance. AB - The authors describe the radiologic appearance of fluid silicone in the soft tissues of the gluteal area in a transsexual man. Thickening and striation of the soft tissues was observed in the trochanteric area in plain films. Serpiginous hyper-attenuated bands infiltrating the subcutaneous fat were seen with computed tomography. The patient was asymptomatic in the gluteal area. PMID- 8348361 TI - Spontaneous perirenal urinoma secondary to cervical carcinoma: diagnosis and management. AB - Formation of a urinoma secondary to obstruction by a tumour is rare. The authors report a case of perirenal urinoma secondary to cervical carcinoma; the urinoma was drained percutaneously. The diagnosis and management of this problem are reviewed. PMID- 8348362 TI - Computed tomography and ultrasonography findings for an adult with Shwachman syndrome and pancreatic lipomatosis. AB - The authors present a case of pancreatic lipomatosis in an adult patient with exocrine pancreatic insufficiency and bone marrow dysfunction (Shwachman syndrome). Ultrasonography demonstrated a morphologically normal pancreas, whereas computed tomography revealed diffuse pancreatic lipomatosis. PMID- 8348363 TI - Communicating intraosseous ganglion of the lunate. AB - The authors describe a symptomatic intraosseous ganglion of the lunate communicating directly with the scapholunate joint. The communication was demonstrated by arthrography and computed tomography. This case is believed to be the first reported in which the communication was shown by arthrography. Demonstration of such a communication can obviate the need for further imaging to diagnose the lesion. A review of intraosseous ganglia of the hand and their treatment is presented. PMID- 8348364 TI - Magnetic resonance imaging in the diagnosis of suprascapular nerve syndrome. AB - The authors report the findings in a case of early suprascapular nerve syndrome caused by a ganglion in the spinoglenoid notch. The diagnosis was established by magnetic resonance imaging. The exquisite soft-tissue detail provided by this modality allows differentiation among many causes of shoulder pain. PMID- 8348366 TI - Computed tomography of the sacroiliac joints in children. AB - Clinical assessment of the sacroiliac joints is difficult. Conventional radiography and radionuclide scanning have not afforded optimal sensitivity and specificity in the diagnosis of sacroiliac involvement in spondyloarthropathies. This report describes a technique for computed tomography of the sacroiliac joints in children; the method involves coronal scanning and allows assessment of the entire surface of the joints. PMID- 8348365 TI - Ethanol sclerosis of a mediastinal cyst. AB - The authors report a mediastinal cyst treated by aspiration and ethanol sclerosis, which were performed under ultrasonographic guidance. Mediastinoscopy and thoracotomy were thus avoided. One year later there had been no recurrence of the cyst or any symptoms. PMID- 8348367 TI - Residents' corner. Answer to case of the month #20. Cecal volvulus. PMID- 8348368 TI - Residents' corner. Case of the month #21. PMID- 8348369 TI - Female reproductive physiology and endocrinology of cattle. AB - Maximizing reproductive efficiency is of major economic importance to dairy and beef producers. The development of new and improved methods of increasing reproductive performance depends on our understanding of the physiologic and endocrinologic mechanisms controlling the reproductive process. This article reviews the mechanisms associated with puberty, estrous cycles, pregnancy, parturition, and postpartum return to estrus. PMID- 8348370 TI - Estrous behavior and detection in cattle. AB - Hormonal events determine the timing and maximum duration of estrous behavior, whereas environmental and social factors modulate or completely inhibit the expression of estrus. The efficiency of estrous detection can be improved on most livestock farms if more effort is given to visual observations of estrous behavior. Heat detection aids can be of value if used as a supplement to visual observations. Knowledge of factors that inhibit estrus can help producers avoid or minimize situations that make estrous detection difficult or impossible. Each livestock enterprise should have a customized heat detection program in place because blanket recommendations often fail when applied to many operations. PMID- 8348371 TI - Environmental stress effects on bovine reproduction. AB - Environmental stress is not limited to climatic factors but extends to nutrition, housing, and any stimuli that demand a response from the animal to adapt to new circumstances. Low energy and low or excessive protein levels in the diet are detrimental to reproduction. Likewise, high ambient temperatures and humidity alter the intricate balance of endocrine profiles, leading to lower intensity of estrous behavior, anestrus, embryonic death, and subsequent infertility. Most of these stress factors can be managed with modern technologies to achieve maximum production. Further research in vitamins and minerals under heat stress may add to the knowledge of efficient livestock production. PMID- 8348372 TI - Factors affecting fertility with artificial insemination. AB - Man's intervention in the natural processes of reproduction with the use of AI has allowed rapid genetic improvement in beef and dairy herds and has resulted in a marked increase in livestock productivity. In today's tough economic climate, high reproductive efficiency is of utmost importance for livestock enterprises to remain viable. Many factors affect the success of AI programs; of particular importance are the health and nutritional management of the herd and accurate, efficient heat detection. Good management combined with knowledge, technical expertise and careful attention to detail in the timing of insemination in relation to the period of estrus, semen handling, and correct semen placement in the uterus ensure the successful use of AI. PMID- 8348373 TI - Infertility due to abnormalities of the ovaries in cattle. AB - A careful physical examination of a cow or heifer suspected of having an ovarian problem often results in a specific diagnosis (e.g., freemartinism) or a workable list of differentials. When the diagnosis is uncertain, techniques such as rapid progesterone assays, ultrasonographic imaging, ova or embryo recovery, and cytogenetic evaluation can provide critical information for a well-based diagnosis and prognosis. Despite the wide array of problems that can afflict the bovine ovary, cystic ovaries probably are the most commonly diagnosed and treated ovarian abnormality. Cysts have a variable life span and sometimes occurs together with a CL. Hormonal therapy with either GnRH followed by PG approximately 9 to 14 days later, or GnRH alone, followed by good heat detection is the treatment of choice for cows with cysts. Other conditions associated with ovarian dyfunction and infertility include adhesions, developmental anomalies, and tumors. The life span of a CL in the cow can be shortened unintentionally by attempting to correct other problems (e.g., multiple injections of oxytocin for milk let-down), or lengthened by uterine pathology (e.g., pyometra, or uterus unicornis). The administration of GnRH or hCG to improve ovarian function and pregnancy rates in cows may be beneficial in selected herds. PMID- 8348374 TI - Abnormalities of the tubular genital organs. AB - Abnormalities of the tubular reproductive tract are responsible for decreased fertility in the cow. Typically, these are related to congenital defects such as segmental aplasia or to acquired conditions resulting from infections or trauma caused during breeding or parturition. Infection of the tubular tract may result in vaginitis, cervicitis, metritis, endometritis, pyometra, or salpingitis. Trauma to the tract may result in urovagina, pneumovagina, or prolapse of the vagina or uterus. Retained placenta may result in metritis. Potentially, all of these conditions, unless properly treated, may result in reduced fertility or, in the extreme, sterility. Judicial and properly timed use of antibiotics and ecbolic agents should return the tract to proper function with little or no reduction in fertility. Some conditions, such as prolapse, retained placenta, and pneumovagina, may call for manual or surgical intervention for successful resolution. PMID- 8348375 TI - Abnormal bovine parturition. Obstetrics and fetotomy. AB - The veterinarian is in a unique position to assist and improve the profitability of producers by educating clients on proper intervention and delivery techniques. This paper describes some procedures for intervention, evaluation, and management of dystocia by mutation, forced extraction, and fetotomy. In addition, a brief summary of the factors influencing dystocia is presented. When these techniques are used properly, losses due to dystocia are minimized. PMID- 8348376 TI - Infectious diseases causing bovine abortion and fetal loss. AB - This article provides a review of the major infectious diseases responsible for bovine abortion and fetal loss. Parameters necessary for disease recognition and diagnosis are emphasized. PMID- 8348377 TI - Female urogenital surgery in cattle. AB - Surgical manipulation of the female reproductive tract is part of routine bovine clinical practice. Most indications for urogenital surgery in cattle are for alleviation of dystocia or correction of injuries sustained during parturition. Less frequently, surgery is indicated for ovarian tumor removal, embryo transfer, or spaying of feeding heifers. This article discusses clinical assessment for selection of various surgical procedures of the bovine female genital tract. PMID- 8348378 TI - Fertility and infertility assessment by review of records. AB - The assessment of fertility and infertility in dairy herds requires accurate and complete data that are collected in a timely manner. The data must be entered in a record system that provides easy accessibility. An understanding of terminology and statistical calculations, along with knowledge of industry standards, reproductive physiology, and pathology is essential if problem solving is to occur. Problem solving begins by developing an understanding of the events influencing past reproductive performance. Progress is made by establishing a detailed reproductive management plan to monitor the current breeding herd and to identify potential problems before they occur. The introduction of microcomputers and on-farm record systems has greatly enhanced the veterinarian's ability to access and process data. For the first time in history, cowside health data collection systems integrated with production records are being used. This provides the opportunity to collect and summarize and analyze reproductive and production data as the events occur. Successful reproductive performance depends on effective and efficient management. For veterinarians to effectively and positively influence the reproductive performance of the herd, they must influence management. This requires working with dairy management to make changes in job assignments and description. Taking time to assess records with managers is an invaluable tool to convince dairy management of the necessity for change. PMID- 8348379 TI - Production medicine considerations for enhanced reproductive performance in beef herds. AB - The purpose of this article is to provide considerations that must be included in a production medicine program. Although no two programs are the same, each of these areas must be addressed to be effective. Use of current knowledge and technology as well as emerging knowledge and technology to provide input into management practices for enhancing performance is the underlying goal of any production medicine program. The veterinary practitioner can serve as a participant in establishing and maintaining such a program as part of the complete management team. PMID- 8348380 TI - Effect of estrogen deficiency on IGF-I plasma levels: relationship with bone mineral density in perimenopausal women. AB - Bone tissue is a source of growth factors; among them, insulinlike growth factor I (IGF-I) is probably an important local regulator of bone formation. This study has been carried out in order to assess the effects of natural menopause on plasma concentrations of IGF-I in the first 6 years after the cessation of gonadal function independent of age. We also examined the relationship between plasma IGF-I levels and bone mineral density (BMD) measured at the lumbar spine (LS), at the ultradistal radius (UDR), and at the junction of the distal and middle thirds of the radius (MR). Sixty-seven healthy nonobese women, aged 45-55, were studied (premenopausal n = 21; postmenopausal n = 46, from 1 to 6 years since menopause). Plasma IGF-I levels were measured by RIA, after acid-ethanol extraction. BMD of the forearm was measured by dual-photon densitometer and BMD of the LS was assessed by quantitative digital radiography. Mean values of IGF-I plasma levels were significantly reduced in postmenopausal women compared to the premenopausal group. Menopausal duration did not influence IGF-I plasma levels in postmenopausal women. We also found a positive correlation between IGF-I levels and BMD measured at MR both in pre- and postmenopausal women, while a correlation with LS and UDR-BMD was found only in fertile subjects. The results show that IGF I plasma levels decrease immediately after menopause, since significantly lower levels are reached in the first years. The correlations found between plasma IGF I levels and BMD suggest a possible role of reduced IGF-I in bone loss at particular skeletal sites. PMID- 8348381 TI - Combined treatment with calcitonin and 1,25-dihydroxyvitamin D3 for osteoporosis in women. AB - Twenty-two middle-aged women with severe osteoporosis were treated for 2 years with either 0.5 mg of synthetic human calcitonin subcutaneously three times per week combined with 0.5 micrograms of calcitriol and 0.5 g of calcium per day orally or calcium only. The treatment with calcitonin plus calcitriol (12 patients) resulted in a significantly increased calcium absorption rate. The mean values for serum phosphate did not change during the treatment period and the mean values did not differ between the treatment groups, but the serum calcium and urinary Ca/Cr ratio increased somewhat in the group given the combined treatment. There was no evidence that the combined treatment improved the bone density in this study. It is possible that calcitriol, instead of increasing the effect of calcitonin by suppression of the parathyroid, might have counteracted its effect by increasing the bone resorption. PMID- 8348382 TI - Iron distribution in thalassemic bone by energy-loss spectroscopy and electron spectroscopic imaging. AB - Iron overload occurs frequently in thalassemia as a consequence of regular blood transfusions, and iron has been found to accumulate in bone, but skeletal toxicity of iron is not clearly established. In this study, bone biopsies of thalassemic patients were investigated by light (n = 6) and electron microscopy (n = 8) in order to analyze iron distribution and possible iron-associated cellular lesions. Sections (5 microns thick) were used for histomorphometry and iron histochemistry. Ultrathin sections were examined with an energy filtering transmission electron microscope. Iron was identified by electron energy loss spectroscopy (EELS), and iron distribution was visualized by electron spectroscopic imaging (ESI) associated with computer-assisted treatment (two window method). This study shows that EELS allows the detection of 4500-9000 iron atoms, and that computer-assisted image processing is essential to eliminate background and to obtain the net distribution of an element by ESI. This study shows also that stainable iron was present along trabecular surfaces, mineralizing surfaces, and on cement lines in the biopsies of all patients. Moreover, iron was detected by EELS in small granules (diffusely distributed or condensed in large clusters), in osteoid tissue, and in the cytoplasm of bone cells, but not in the mineralized matrix. The shape and size (9-13 nm) of these granules were similar to those reported for ferritin. As for iron toxicity, all patients had osteoid volume and thickness and osteoblast surface in the normal range. Stainable iron surfaces did not correlate with osteoblast surfaces, plasma ferritin concentrations, or the duration of transfusion therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348383 TI - Selective inhibition of collagen synthesis by fluoride in human pulp fibroblasts in vitro. AB - Human dental pulp cells were cultured in fluoridated mediums (0, 1, 10, 25 ppm) in order to study the biological effect of the ion regarding the cellular metabolism: cell growth, alkaline phosphatase (ALP) activity, and protein synthesis. The results indicated a decrease of the cell growth at 25 ppm and a dose-dependent decrease of the ALP activity. Type I collagen immunoperoxidase staining, radioimmunoassay quantitation, and analysis of type I and III collagens mRNA levels showed an inhibition of collagen production and gene expression. In contrast, fibronectin production and gene expression were not affected by fluoride. The treatment did not influence the qualitative pattern of the different mRNA species. Of the three collagen chains, the alpha 1(I) was the most affected. These data suggest that fluoride does not exert a general depletive effect on human dental pulp cells but rather a selective inhibition on collagen production. PMID- 8348385 TI - Effect of weight manipulation on bone loss due to ovariectomy and the protective effects of estrogen in the rat. AB - While characterizing the effects of estrogen on an ovariectomized (OVX) rat model of bone loss, we examined several weight-matching regimens [e.g., ad libitum (feed bins continually full), weight matched (rate of weight gain for OVX and Sham-OVX groups was equalized), and weight restricted (weight gain rates for all groups were equalized to that of estrogen-treated OVX rats)] for possible effects. Bone loss following ovariectomy is primarily the result of an increase in bone resorption and is extremely sensitive to the effects of estrogens. Thus, in all of our analyses, treatment with 17 beta-estradiol served as a positive control for the prevention of bone loss. Each weight-matching study had three groups: control (Sham-OVX), OVX, and OVX + 17 beta-estradiol (0.1 mg/kg/day), and lasted for either 2, 4, or 6 weeks. Throughout the study, each Sprague Dawley rat was weighed every other day, and following sacrifice, a femur was removed for bone mineral density (BMD) analysis at the distal metaphysis by single photon absorptiometry. Following 2 weeks of dietary modifications, no significant differences were detected in BMD among the ad lib or weight matched groups. However, an estradiol-preventable reduction in BMD in restricted OVX rats was detected at 2 weeks postovariectomy. Additionally, OVX rats in all three dietary regimens displayed an estrogen-preventable reduction in proximal femur BMD at 4 and 6 weeks postovariectomy. These results indicate that a 4-week rat ovariectomized model of bone loss, under conditions of ad libitum feeding, shows great potential for pharmacologic manipulation. PMID- 8348384 TI - Lack of change of cancellous bone volume with short-term use of the new immunosuppressant rapamycin in rats. AB - Immunosuppressants have adverse effects on bone mineral metabolism in animal and human studies, with corticosteroids producing low-turnover osteopenia, and cyclosporin-A (CsA) producing high-turnover osteopenia. Rapamycin (RAPA) is a new immunosuppressant reported to be at least 10 times more potent than CsA, and acts via a different pathway to CsA and the other new immunosuppressant FK506. This study investigated the effects of RAPA on bone mineral metabolism in the rat. Forty-two, 10-week-old, male Sprague Dawley rats were divided into three groups, and treated according to the following protocol: group A (control) received RAPA vehicle by daily gavage for 14 days (n = 12); group B (high dose RAPA) received RAPA 2.5 mg/kg/day by daily gavage for 14 days (n = 15); group C (low dose RAPA) received RAPA 1.25 mg/kg/day by daily gavage for 14 days (n = 15). Rats were weighed and bled on days 0, 7, and 14 for measurement of blood ionized calcium, bone Gla protein (BGP), parathyroid hormone (PTH), and 1,25(OH)2D. Tibial bone histomorphometry was determined on day 14 after double-calcein labeling. Weight gain was similar in the two groups treated with RAPA compared with control animals. High-dose RAPA (group B) transiently depressed serum BGP levels on day 7, with elevated blood ionized calcium levels on day 7, and lowered 1,25(OH)2D levels on day 14. Serum PTH levels were unchanged. Low-dose RAPA (group C) did not affect calciotropic hormones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348386 TI - Presence of lactate dehydrogenase-containing vesicles in an intramembranous ossifying tissue: new-born mouse calvaria. AB - Lactate dehydrogenase-containing vesicles have been isolated from the extracellular matrix of the calvaria of new-born mice. The calvariae, intramembranous ossification tissue, were removed from 2-day-old mice, followed by the separation of the extracellular matrix vesicle fraction after collagenase digestion. Lactate dehydrogenase-containing vesicles with a density different from that of matrix vesicles were detected in the matrix vesicle fraction. Lactate dehydrogenase in these vesicles did not result from cell lysis and vesicle capture during the preparation of the matrix vesicle fraction. The isoenzyme pattern of lactate dehydrogenase in lactate dehydrogenase-containing vesicles was nearly identical to that of cytosolic lactate dehydrogenase of the cell fraction. Other cytosolic enzymes were not detected in lactate dehydrogenase containing vesicles, suggesting the presence of a mechanism for specific uptake of cytosolic lactate dehydrogenase during the in vivo formation of the vesicles. This is the first report on the presence of lactate dehydrogenase-containing vesicles in the intramembranous ossification site. PMID- 8348387 TI - Regional and total body bone mineral content, bone mineral density, and total body tissue composition in children 8-16 years of age. AB - Normative values for total body bone mineral content (TBBM) and total body bone mineral density (TBMD) were derived from measurements on 234 children 8-16 years of age. In addition, bone mineral content (BMC) and bone mineral density (BMD) values for selected regions of interest and soft tissue (bone free lean and fat) for the total body are presented. Bone mineral and soft tissue values were determined by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-2000 in the array mode. Results of a stepwise multiple regression analysis revealed a significant correlation between bone-free lean tissue (BFLT) and BMD (r2 = 0.80) in girls. Adding age to the equation accounted for an additional 2% of the variance (P < 0.05) and height accounted for another 1% of the variance (P < 0.05). Body weight and fat tissue (FT) did not account for any additional variance. In boys BFLT correlated significantly with BMD (r2 = 0.75; P < 0.05); none of the other predictor variables accounted for additional variance. No significant differences were found in TBBM or TBMD between boys and girls at any age. There was a significant overall gender effect for only three regions of interest. Boys had greater BMC in the head region and had greater BMD in the upper limbs, but post hoc analysis revealed no significant differences for any specific age groups. Girls had greater overall BMD in the pelvis, but this difference was only significant at the 15-16-year age group. The changes in BFLT and FT over the age ranges were consistent with the growth literature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348389 TI - Cellular immunodeficiency in Paget's disease of bone. PMID- 8348388 TI - Lack of effect of ipriflavone on osteoclast motility and bone resorption in in vitro and ex vivo studies. PMID- 8348390 TI - Ethical issues for cardiovascular physicians. Ethics Committee, Canadian Cardiovascular Society. PMID- 8348391 TI - Calcium antagonists in heart transplant recipients: effects on cardiac and renal function and cyclosporine pharmacokinetics. AB - OBJECTIVE: Cyclosporine increases transmembrane calcium flux in mesangial and vascular smooth muscle cells, which may explain cyclosporine-induced decreases in renal bloodflow and glomerular filtration rate. Calcium antagonists, thus, may play a role in the prevention/reversal of cyclosporine nephrotoxicity. DESIGN: In a single-blind, randomized, cross-over study the authors evaluated the effects of a one-week treatment with nifedipine 20 mg bid, diltiazem 120 mg bid or placebo on cardiac and renal functions of six stable heart transplant recipients treated chronically with cyclosporine. RESULTS: Both calcium antagonists lowered blood pressure compared with placebo, but only nifedipine increased cardiac output and, therefore, decreased total peripheral resistance significantly more than diltiazem. Nifedipine induced a significant increase in effective renal plasma flow and an insignificant increase in glomerular filtration rate, whereas diltiazem caused a reduction in these parameters. Cyclosporine pharmacokinetics were not affected by either calcium antagonist to a clinically significant extent. CONCLUSIONS: Nifedipine and diltiazem exert distinctly different cardiac and renal hemodynamic effects in cardiac transplants, which may have clinical consequences. PMID- 8348392 TI - Comparison of the short term efficacy and tolerability of lovastatin and simvastatin in the management of primary hypercholesterolemia. AB - OBJECTIVES: To compare the safety and efficacy of lovastatin and simvastatin in patients with primary hypercholesterolemia. METHODS: Fourteen Canadian centres participated in this double-blind, randomized, parallel-design study with a six week screening period, a four-week placebo baseline period and an 18-week active treatment period. Patients were included in the study if their total cholesterol (TC) was at least 6.2 mmol/L and total triglycerides (TG) were 4.0 mmol/L or less at baseline. Half of the patients were in stratum I (TC 6.2 to 7.8 mmol/L at baseline and placebo period) and half in stratum II (TC greater than 7.8 mmol/L). The initial dose of lovastatin or simvastatin (20 and 10 mg/day, respectively) was doubled if the patient's cholesterol was greater than 5.2 mmol/L after six and/or 12 weeks, to a maximum of 80 mg/day lovastatin or 40 mg/day simvastatin. Of 298 randomized patients, two had baseline data only (and were excluded from the efficacy analysis), while 77 were treated with lovastatin and 74 with simvastatin in stratum I, and 72 were on lovastatin and 75 on simvastatin in stratum II. RESULTS: In stratum I, both lovastatin and simvastatin lowered TC ( 26.0% in both the lovastatin and simvastatin groups), low density lipoprotein (LDL) cholesterol (-33.4% in lovastatin and -34.4% in simvastatin), TG (-11.4% in lovastatin and -16.2% in simvastatin), apolipoprotein (apo)-B (-24.8% in lovastatin and -26.3% in simvastatin) and the TC:high density lipoprotein (HDL) cholesterol ratio (from 6.65 to 4.73 in lovastatin and from 6.45 to 4.46 in simvastatin), and increased HDL cholesterol (+3.6% in lovastatin and +7.8% in simvastatin) and apo-A1 (+6.3% in lovastatin and +9.0% in simvastatin) with P < 0.001 in all within-group tests except for HDL cholesterol (P < 0.05). Similar results were obtained in stratum II for TC (-30.7% in lovastatin and -30.3% in simvastatin), LDL cholesterol (-37.6% in lovastatin and -36.8% in simvastatin), TG (-21.9% in lovastatin and -16.9% in simvastatin), apo-B (-32.0% in lovastatin and -31.7% in simvastatin), TC:HDL cholesterol ratio (from 8.62 to 5.47 in lovastatin and from 8.96 to 5.77 in simvastatin), HDL cholesterol (+9.7% in lovastatin and +7.5% in simvastatin) and apo-A1 (+7.2% in lovastatin and +8.8% in simvastatin), with P < 0.001 in all within-group tests. Serious adverse events (clinical and laboratory) were reported in four patients in the lovastatin group and three in the simvastatin group. The most reported nonserious adverse effects were gastrointestinal tract (15 patients in the lovastatin group and 16 in the simvastatin group) and musculoskeletal (14 patients in the lovastatin group and 11 in the simvastatin group). Medication was withdrawn in eight patients. CONCLUSIONS: Both lovastatin and simvastatin were found to be effective and well tolerated in each stratum. However, there were no significant differences between lovastatin and simvastatin in the treatment of moderate or severe primary hypercholesterolemia. PMID- 8348393 TI - Long term clinical outcomes following isolated mitral valve replacement. AB - OBJECTIVE: This study reviews the short and long term outcomes of patients who underwent isolated mitral valve replacement at the University of Alberta Hospitals during the past decade. DESIGN: Data were obtained retrospectively by review of patients' hospital charts, cardiologists' follow-up charts, contact with patients' physicians, and direct telephone or mail contact with patients and/or their surviving relatives. RESULTS: The clinical outcomes of 198 consecutive patients (124 women and 74 men) who underwent isolated mitral valve replacement from January 1981 to December 1990 at the University of Alberta Hospital were reviewed. Overall early operative mortality was 11%. Deaths were mainly related to pump failure and previous mitral valve replacement. Late mortality was 17%. Follow-up data were available except in five patients. Average follow-up was 6.3 years. Overall cumulative survival was 72.9 +/- 3.4% at five years and 63.1 +/- 4.8% at 10 years. The cumulative freedom from complications was 64.3 +/- 3.9% and 36.4 +/- 4.9% at five and 10 years, respectively. Long term survival rates obtained after isolated mitral valve replacement are higher than those reported in series of medically treated patients with mitral valve disease. CONCLUSIONS: Mitral valve replacement can prolong survival as well as improve symptoms in patients with symptomatic mitral valve disease. PMID- 8348394 TI - Intractable ventricular arrhythmias during remodelling and healing after acute myocardial infarction. AB - A patient with extensive myocardial infarction, evidence of early ventricular remodelling, regional left ventricular (LV) dilation and aneurysm formation developed recurrent ventricular tachyarrhythmias and episodes of sudden death. The patient finally died 24 days post infarction despite effective anti remodelling therapy and appropriate anti-failure and anti-arrhythmic therapies. Remarkable findings at autopsy included normal LV size and a small LV apical aneurysm despite as much as 52% LV necrosis and further right ventricular necrosis. The case underscores the need for aggressive early infarct-limiting therapy to prevent early remodelling, LV aneurysm and possibly fatal ventricular tachyarrhythmias. PMID- 8348395 TI - Paradoxical embolism-in-transit: diagnosis and surgical treatment. AB - Paradoxical embolism-in-transit is an uncommon presentation of the thromboembolism complex. The advent of echocardiography has permitted its antemortem diagnosis and serves to guide treatment; this is illustrated by the case of a 51-year-old female who presented with paradoxical embolism-in-transit and pulmonary embolism following craniotomy. Echocardiography demonstrated mobile clot straddling the atrial septum and embolus in the right pulmonary artery. Surgery successfully removed all clots as demonstrated by intraoperative echocardiography, and the patient had an uneventful recovery. PMID- 8348396 TI - Right atrial myxoma originating from the eustachian valve. AB - An unusual case of multiple right atrial myxomas arising from the interatrial septum and the Eustachian valve is reported. The literature contains reports of only one other patient with a right atrial myxoma originating from the Eustachian valve. PMID- 8348397 TI - Unilateral "vanishing psoas": an anatomic variant. AB - We report five patients found to have obvious asymmetry of the psoas muscles on abdominal computed tomography (CT) examination. In all five patients, the upper portion of the psoas muscle was normal, but the lower portion was significantly reduced in size. In no patient was there neurological or other disease that might explain this finding. No patient exhibited signs or symptoms secondary to psoas asymmetry. Asymmetry of the psoas musculature is apparently a benign anatomical variant that may be recognized on CT examination and must be differentiated from pathological conditions. PMID- 8348398 TI - Cavernous hemangioma of the kidney. Case report. AB - Renal hemangiomas are rare neoplasms of the kidney, and the number of cases reported in the literature are about 200 since the original description by Virchow in 1867. Among these, only a few have been examined by the combination of ultrasound, computed tomography, and angiography. We present a demonstrative case diagnosed at our clinic and review the corresponding literature. PMID- 8348400 TI - Smooth muscle tumors of the inferior vena cava and right heart. AB - Four Chinese patients with extensive smooth muscle tumors of the inferior vena cava (IVC) and right heart are described. Two patients had primary IVC leiomyosarcomas and one had both IVC and cardiac metastases from uterine leiomyosarcoma. The remaining patient had extra-uterine intravenous leiomyomatosis, with extensive tumor calcification. Clinical presentation was variable, consisting of the Budd-Chiari syndrome, a new heart murmur, and signs of cerebral embolism. All the lesions were defined radiologically prior to surgical resection of cardiac tumors. PMID- 8348399 TI - Mesenteric panniculitis presenting as a multilocular cystic mesenteric mass: CT and MR evaluation. AB - Mesenteric panniculitis is a non-neoplastic, inflammatory process affecting the adipose tissue of the mesentery in adults with slight male predilection. Typical computed tomography (CT) or magnetic resonance imaging (MRI) findings are of either diffuse mesenteric infiltration or nodular mesenteric masses. We encountered a case of mesenteric panniculitis in a 26-year-old woman with the left upper quadrant pain and fullness, in which CT and MRI disclosed a large, ill defined, multilocular cystic mesenteric mass. After surgery, the diagnosis of mesenteric panniculitis was made. The cystic components were dilated lymphatics due to lymphatic and venous obstruction by the mesenteric panniculitis. PMID- 8348401 TI - Angulated needle placement in CT-guided percutaneous needle biopsy of the thorax. AB - Computed tomography (CT)-guided percutaneous needle biopsy is often necessary to evaluate small intrathoracic lesions. Not infrequently, an overlying structure such as a rib or vessel precludes insertion of the biopsy needle within the CT slice containing the lesion. Insertion and angulation of the needle at a site within an adjacent CT slice is then required. In order to determine the optimal skin-entry site and degree of angulation for biopsy needle insertion, we analyzed the geometric relationship between lesion depth, needle length, and needle angulation. PMID- 8348402 TI - Magnetic resonance imaging and computed tomography appearance of asymptomatic paravaginal cysts. AB - The magnetic resonance imaging (MRI) and computed tomography (CT) appearance of 18 paravaginal cysts was reviewed. On MRI, serious cysts were hypointense on T1 weighted and hyperintense on T2-weighted images. Cysts presumed to contain proteinaceous material were hyperintense on T1-weighted and T2-weighted sequences while hemorrhagic cysts exhibited varying stages of hemorrhage. On CT, a high attenuation cyst was presumed to contain proteinaceous material or hemorrhage. MRI and CT examination may reveal paravaginal cysts; their varied appearance must be recognized to avoid confusion with other lesions. PMID- 8348403 TI - Cranial magnetic resonance imaging in Lowe's syndrome. PMID- 8348405 TI - Magnetic resonance imaging of hemorrhagic acoustic neuroma. AB - A rare case report of a large hemorrhage acoustic neuroma is described with computed tomography and magnetic resonance imaging findings. Magnetic resonance imaging provides precise definition of the hemorrhage and relationship of the tumor to surrounding structures. PMID- 8348404 TI - Ossicles anterior to the proximal tibia. AB - Ossicles anterior to the anterior tibia are most usually seen in relation to the tibial tuberosity. While these are usually taken to represent sequelae of previous Osgood-Schlatter disease, they may, on occasion, represent normal variants in ossification of the tuberosity. Ossicles superior to the tuberosity may have similar origins. Representative examples are presented, as is a very large ossicle separated from the anterior tibia by a prolongation of the knee joint space. Theories of causation of such ossicles are discussed. PMID- 8348406 TI - Large epidermal cyst involving the ischiorectal fossa: MR demonstration. AB - A large subcutaneous mass was noted in the buttock of a 79-year-old man. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a thin-walled cystic mass that involved the ischiorectal fossa. The content appeared hyperintense on T1-weighted images. T2-weighted images demonstrated a considerable amount of debris. At surgery an epidermal cyst with markedly keratinized squamous epithelium was found. It contained much keratin and cholesterin. PMID- 8348407 TI - Retroperitoneal extraosseous Ewing's sarcoma with renal involvement: US and MRI findings. AB - A case of retroperitoneal extraosseous Ewing's sarcoma (EES) with renal involvement, which simulated an exophytic renal mass, is reported. EES is a rare soft tissue tumor that can occur anywhere in the soft tissues, but is seen most commonly in the extremities. Although EES is histologically similar to osseous Ewing's sarcoma, it is usually found in older patients. EES should be included in the differential diagnosis of soft tissue tumors, especially in the second and third decade of life. PMID- 8348408 TI - Giant cell tumor of the plantar tendon sheath: role of MR imaging in diagnosis. Case report. AB - Giant cell tumor of the tendon sheath with characteristic magnetic resonance imaging findings is reported. The tumor was low intensity on T1-weighted and T2 weighted images, and showed strong homogeneous enhancement. These findings were considered to represent the pathological features of fine hemosiderin granules and collagenization. PMID- 8348409 TI - Spectrum of CT and sonographic appearance of fatty infiltration of the liver. AB - This report presents the common and unusual appearances of fatty infiltration of the liver (FIL) on ultrasound (US) and computerized tomography (CT) from pathological, proven cases. Potential diagnostic pitfalls and methods of avoiding these pitfalls will be emphasized. Generalized and the geographic pattern of FIL are well recognized. Focal FIL and focal sparring of the liver have a number of atypical appearances. Focal sparring has several distinct patterns (pseudotumor, glove pattern and possible metastasis), which may be confused with other pathologies. Likewise, focal FIL may simulate a space-occupied mass. Among the more helpful features used to distinguish focal FIL from other abnormalities include its lack of mass effect, low density on CT combined with increased echogenicity on US. PMID- 8348410 TI - Normal anatomic variation: a never ending saga. PMID- 8348411 TI - Pancreatic adenocarcinoma presenting with ureteric metastases. Case report and review of literature. AB - We report a patient with pancreatic adenocarcinoma presenting with ureteric metastases. A low index of suspicion led to incomplete radiographic evaluation, and the etiology could not be established prior to laparotomy. The differential diagnosis of ureteric strictures is reviewed, with a view to providing a simple diagnostic flow chart that should prove satisfactory in all but the most exceptional cases. PMID- 8348412 TI - Canadian Ophthalmological Society. 56th Annual Meeting. June 27-29, 1993, Montreal, Quebec. Programme and abstracts. PMID- 8348413 TI - Heaven in the United States? PMID- 8348414 TI - Heaven in the United States. PMID- 8348415 TI - Ciprofloxacin advertising in CMAJ. PMID- 8348416 TI - Screening for genetic disease. PMID- 8348417 TI - Childhood sexual abuse. PMID- 8348418 TI - Vitamin D supplementation. PMID- 8348419 TI - CT scanning in meningitis. PMID- 8348420 TI - Nurse practitioners. PMID- 8348421 TI - Addressing the pharmaceutical industry's influence on professional behaviour. PMID- 8348422 TI - Development of residency program guidelines for interaction with the pharmaceutical industry. Education Council, Residency Training Programme in Internal Medicine, Department of Medicine, McMaster University, Hamilton, Ont. AB - Medical residency programs are likely to face increasing pressure to address their relations with the pharmaceutical industry. Our internal medicine residency program has developed guidelines that were adopted after extensive debate by residents and faculty members. The guidelines are based on the principles that residents and faculty should set the educational agenda and that the residency program should not allow gifts of any sort from industry to residents. Specific policies include obtaining and screening educational materials from the industry before residents are exposed to them, proscribing "drug lunches" and accepting industry sponsorship only when the residency program maintains complete control of the educational event being sponsored. The industry response to the guidelines was split; about half reacted negatively, and half found the guidelines acceptable. Our experience suggests that productive debate about guidelines for the interaction of residency programs with the pharmaceutical industry is possible and desirable and that explicit policies can clarify areas of ambiguity. PMID- 8348424 TI - Risk factors for extended disruption of family function after severe injury to a child. AB - OBJECTIVE: To identify risk factors for long-lasting disruption of family function following pediatric trauma that can be measured at the time of trauma. DESIGN: Prospective, exploratory study. Personal interviews were conducted at the time of admission and 6 months and 1 year after discharge. SETTING: Level I regional pediatric trauma centre. PARTICIPANTS: One hundred and five families (86% of those eligible) with a child admitted to hospital for severe trauma with an Abbreviated Injury Scale (AIS) score of 4 or higher or with two or more injuries in different body parts and AIS scores of 2 or higher were recruited; 13 families were lost to follow-up at 6 months or 1 year, so their data were not included in the analyses. MAIN OUTCOME MEASURES: Family function status (normal or abnormal compared with function before the injury), demographic characteristics of the parents and child, injury severity, presence of maternal psychologic disorder, presence of child behaviour abnormality and functional status of the child. MAIN RESULTS: At 6 months and at 1 year 41 families (45%) and 21 families (23%) respectively reported that their family lives had not returned to normal. The relative odds for disruption of family life were about five times higher (95% confidence limits [CL] 1.4 and 19.7) and four times higher (95% CL 1.1 and 14.0) for single-parent families than for families with married parents living together at 6 months and 1 year respectively. The presence of maternal psychologic disorders at admission and increased age of the injured child were also significantly associated with extended disruption of family function. Injury severity and functional status at discharge were not good predictors of family function. CONCLUSIONS: Severe injury to a child places a heavy strain on normal family function. In particular, single parents and parents experiencing mental or emotional problems at the acute stage of the injury need help in coping with their reactions to the trauma and may benefit from individual or group counseling. PMID- 8348426 TI - Neural regeneration research offers hope. PMID- 8348425 TI - Elective repeat cesarean sections: how many could be vaginal births? AB - OBJECTIVE: To determine (a) the proportion of women undergoing elective repeat cesarean section without a trial of labour who were eligible for such a trial by the 1986 guidelines of the panel of the National Consensus Conference on Aspects of Cesarean Birth, (b) whether vaginal birth after cesarean section (VBAC) was discussed with these women and (c) the reasons cited for not having a trial of labour. DESIGN: Chart audit. SETTING: Level 2 perinatal care centre in a general teaching hospital. PATIENTS: All 313 women with a history of previous cesarean section who gave birth at the centre during 1989. RESULTS: Only 93 (30%) of the 313 women underwent a trial of labour. According to the 1986 guidelines 71% were eligible. A further 13% would have been eligible according to the revised 1991 guidelines. Of the 220 women who underwent elective repeat cesarean section, only 24 (11%) had a discussion of VBAC noted in their hospital charts. However, of all 117 patients whose charts indicated discussion of VBAC 93 (79%) chose to try it. Most of the women had either questionable indications or no indication noted for undergoing repeat cesarean section. CONCLUSION: Most of the women who underwent repeat cesarean section were eligible for a trial of labour. However, few charts noted a discussion of VBAC. Further physician and patient education is necessary to promote the appropriate use of VBAC and repeat cesarean section. PMID- 8348427 TI - DNA typing has become an important police tool. PMID- 8348423 TI - Report of the Canadian Hypertension Society Consensus Conference: 2. Diagnosis of hypertension in adults. AB - OBJECTIVE: To update recommendations for the diagnosis of mild hypertension in adults and to assess the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring. DATA SOURCES: Literature reviews of previous consensus conferences were updated with searches of MEDLINE for the period Jan. 1, 1988, to Nov. 15, 1991, and supplemented by reference lists and personal files. STUDY SELECTION: Panel members selected relevant articles and rated them according to methodologic criteria. DATA EXTRACTION: The data extracted concerned the measurement of blood pressure, the diagnosis of hypertension, the treatment of mild hypertension, and the reliability and validity of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring in the diagnosis of mild hypertension. The recommendations made were graded according to the level of evidence available, circulated to many experts and approved at a consensus conference. MAIN RESULTS: Previous recommendations for the accurate measurement of blood pressure remain mostly unchanged. Antihypertensive treatment should be prescribed for patients (including the elderly) with an average diastolic blood pressure of at least 100 mm Hg, for those with isolated systolic hypertension (systolic blood pressure of at least 160 mm Hg and diastolic blood pressure of less than 90 mm Hg) and for patients with a diastolic blood pressure of 90 to 99 mm Hg and target-organ damage. Clinical judgement is required in treating patients with a diastolic blood pressure of 90 to 99 mm Hg without target-organ damage, and individual risk for cardiovascular disease must be taken into account. There is insufficient evidence to warrant the routine use of echocardiography, self-measurement of blood pressure or ambulatory blood pressure monitoring in diagnosis. CONCLUSIONS: Recent high-quality evidence supports several new recommendations for the diagnosis of mild hypertension in adults. Additional research is needed to determine the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring. PMID- 8348428 TI - SOGC says regulatory agencies stalling on approval of safe, effective contraceptives. PMID- 8348429 TI - Walk-jog prescription introduced by Toronto centre now a mainstay of cardiac rehabilitation. PMID- 8348430 TI - A Canadian doctor in Zaire. PMID- 8348431 TI - Canadian lawyer at Harvard a mainstay behind calls to change response to medical malpractice. PMID- 8348432 TI - Traditional Chinese medicine becoming another health care option for Canadians. PMID- 8348433 TI - The red face: historical considerations. PMID- 8348434 TI - The red face in domestic animals. PMID- 8348435 TI - The red face: flushing disorders. PMID- 8348436 TI - The red face: rosacea. PMID- 8348437 TI - The red face: atopic dermatitis. PMID- 8348439 TI - The red face: lupus erythematosus. PMID- 8348438 TI - The red face: seborrheic dermatitis. PMID- 8348440 TI - The red face: dermatomyositis. PMID- 8348441 TI - The red face: photogenodermatoses. PMID- 8348442 TI - The red face: physical erythemas. PMID- 8348443 TI - The red face: contact and photocontact dermatitis. PMID- 8348444 TI - The red face: chronic actinic dermatitis. PMID- 8348445 TI - The red face: erysipelas. PMID- 8348447 TI - The red face: cutaneous lymphomas. PMID- 8348446 TI - The red face: drugs, chemicals and other causes. PMID- 8348448 TI - Where are the transformational leaders? PMID- 8348449 TI - Development of a psychiatric home care program and the role of the CNS in the delivery of care. PMID- 8348450 TI - Response to Samulski. PMID- 8348451 TI - Mind-body connection: enhancing healing through imagery. PMID- 8348452 TI - Imagery: a strategic intervention to empower clients. Part I--Review of research literature. AB - This article is the first of a two-part series on the use of imagery in nursing practice. Imagery, an ancient healing technique, is a cognitive tool that acts as a communication mechanism among perception, emotion, and bodily change. Research has found that imagery can help reduce pain and stress, alter the course of disease, and improve clients' outlook on their illness. Imagery engenders a feeling of control and gives the client an effective tool for self-care. This article presents an overview of the history of imagery in medicine and nursing, discusses different types of imagery, and examines possible uses for imagery in a CNS's practice. Finally, recent research studies of imagery in nursing, psychology, and medicine are examined. The second article will help the nurse learn to use imagery in practice and will include a detailed imagery script. PMID- 8348454 TI - Informed consent and vulnerable subjects. PMID- 8348453 TI - Spiritual needs and interventions: comparing the views of patients, nurses, and chaplains. AB - Because of the current trend to use the term spiritual in a broad context that includes religious aspects as a component, along with others such as transcendence and relational aspects, it is essential to clarify what people mean when they use the term. The researchers designed a descriptive (qualitative) study to collect interview data to determine how patients, nurses, and chaplains currently are defining the phrases spiritual needs and spiritual interventions. The researcher interviewed and recorded the responses of 19 surgical patients, 12 nurses, and 7 chaplains to identify their definitions and the specific interventions they thought nurses and chaplains should use to meet spiritual needs. The interviews were analyzed and definitions of spiritual needs were classified according to six categories: religious, values, relationships, transcendence, affective feeling, and communication. Respondents identified five common nursing interventions: prayer, scripture, presence, listening, and referral. PMID- 8348455 TI - Group functioning of a collaborative family research team. AB - Collaborative research teams are an attractive means of conducting nursing research in the clinical setting because of the many opportunities that collaboration can supply. These opportunities include a chance to: (1) network with other nurses who have similar interests, (2) share knowledge and expertise for designing clinical studies that directly affect daily practice, (3) develop instruments, (4) write grant proposals, (5) collect and analyze data, and (6) prepare manuscripts for publication. The effectiveness of research teams, however, is strongly influenced by group functioning. This article describes the functioning of a collaborative family interventions research team of nursing faculty members and CNSs at a large Midwestern university setting. The formation of the group and membership characteristics are described, along with strategies used to identify the research focus and individual and group goals. Aspects related to the influence of the group on members and the internal operations of the group are also addressed. Future strategies to be explored will focus on the size of the group and joint authorship issues. The authors also set forth a number of recommendations for development of collaborative research groups. PMID- 8348456 TI - Identification of confusion among the elderly in an acute care setting. AB - An exploratory, descriptive study was conducted in a large acute care hospital to determine: (1) the indicator/descriptors used by staff nurses to arrive at the diagnosis of confusion, and (2) which indicators/descriptors are perceived as most significant in such a diagnosis. In addition, because the literature frequently cites the occurrence of nurses stereotyping patients as confused and thereby treating them as confused (Libow's self-fulfilling prophecy), the third question explored was the type and quantity of information that was given to nurses at intershift report. A self-constructed interview schedule was used on a sample of 25 staff nurses who were primary caregivers of a confused patient on a given day. Content analysis revealed emergent themes of confusion in two domains: cognitive and behavioral. The findings from this study revealed nurses used cognitive descriptors more frequently to diagnose confusion; however, a large majority of nurses used a combination of both cognitive and behavioral descriptors for diagnosis. Nurses also used independent assessment based on their own observations rather than those from the night nurse in arriving at a nursing diagnosis of confusion. This investigation responds to the need to "confirm defining characteristics of the phenomenon of confusion" posited by Foreman. In addition, results from this study will provide a basis for a taxonomy on the phenomenon of confusion. It is hoped that such a taxonomical classification will enable nurses to assess the confused patient more effectively. PMID- 8348458 TI - Divorced? PMID- 8348457 TI - Product evaluation for cost containment. PMID- 8348459 TI - Factors that influence CNSs' decision about specialization. AB - Few studies have explored nurses' decision making relative to advanced practice. The purposes of this study were to determine when the decision to prepare as a CNS in a particular specialty is made and to identify the factors that influence that decision. A survey was completed by 257 CNSs. Results indicated that more than half (69%) decided on their specialty after graduation from a basic nursing program. The factors that influenced choice of specialty included experience in first position (47%), clinical role model (37%), and student experience (35%). Critical care was rated the most desirable specialty and psychiatric nursing the least preferred. PMID- 8348461 TI - Reverence for the old. PMID- 8348460 TI - Validating a compendium of goals and objectives for educating CNS students in ambulatory care. AB - In fall 1990, the Department of Veterans Affairs launched a Pilot Ambulatory Care and Education program that has as its major goal the shift from a traditional inpatient specialty-based focus of patient care and health professional education to a more forward-looking outpatient generalist-based focus of care and education. The generalist and specialist focus of the CNS role has been introduced in this innovative ambulatory care program. Formal and informal educational opportunities for interdisciplinary team members and students abound. This article describes the development and validation of a compendium of goals and objectives for educating CNS students in ambulatory care. PMID- 8348462 TI - Executive practice. Transition is risky business. PMID- 8348463 TI - Strategies to limit CNS malpractice liability exposure. AB - The number of nurses named as defendants in medical malpractice cases is increasing. The CNS may be especially vulnerable in this legal climate. The complexity and diversity of the CNS role expose the CNS to an increased risk of malpractice liability in a variety of situations. Malpractice judgments and verdicts are used to describe the legal milieu that the CNS practicing in the various roles may encounter. The CNS roles examined are that of: clinician, educator, consultant, and researcher. The liabilities inherent in each of the CNS roles are defined, as well as strategies to limit malpractice liability exposure. PMID- 8348464 TI - Case management: a model of CNS practice. AB - Case management has been widely implemented as a new health care delivery model. The case manager has the pivotal role in the model. The CNS, having the clinical expertise, clinical judgment, and leadership, best suits the case manager's role. As a case manager, the CNS enacts the five role components: expert practitioner, educator, consultant, researcher, and manger. Case management, therefore, can be considered as a model of CNS advanced practice. PMID- 8348465 TI - Extrapyramidal symptoms: a challenge for the consultant. PMID- 8348466 TI - Bill C-30 and Canadian Psychiatry. PMID- 8348467 TI - Psychiatric networks in Canada. PMID- 8348468 TI - The Greater Vancouver Mental Health Service Society: 20 years' experience in urban community mental health. AB - Caring for people in the community with persistent and disabling mental illnesses presents a major challenge to government, planners and mental health professionals. The success with which mentally disabled people are integrated into community life says much about the society in which we live. This article describes the experience of the Greater Vancouver Mental Health Service Society in offering community-based mental health services to persons with schizophrenia and other major mental disorders over the past 20 years. The key to its success lies in a decentralized, relatively non hierarchical organizational structure which allows committed and skilled multidisciplinary teams to work with patients and their families in their community. The resulting services are fully integrated within the fabric of the community and are responsive to local needs. Partnerships among professionals, patients, families and community agencies result in work that is creative, productive and effective. PMID- 8348469 TI - The Hamilton (McMaster) psychiatric network: the evolution of an integrated network of psychiatric services. AB - For 25 years, the Hamilton-Wentworth region has had a well integrated network of psychiatric services. The initial impetus for its establishment came from the founders of the Department of Psychiatry at McMaster University in 1967. They envisaged a regional network of services that integrated the resources of a community-focused university department with those of local community agencies and other mental health care professionals. Over the years, the evolution of the network has been shaped by changes in the size and composition of the faculty, the emergence of additional clinical services and community programs, new directions in the field of psychiatry and changing economic forces and social values. PMID- 8348470 TI - Psychiatric networks: they make sense, but do they work? AB - With a trend toward coordinated networks of mental health services, it is necessary to be able to assess their impact. This paper outlines an approach to network analysis, using a variety of methodologies to come up with a composite picture. Areas to examine include the network processes, such as its goals, functions, structures, outcomes, and the satisfaction of all involved. PMID- 8348471 TI - New onset rapid cycling bipolar disorder in an 87 year old woman. AB - New onset rapid cycling bipolar disorder is rare in late life. The authors report the case of an 87 year old woman who first developed this disorder at age 82 and was successfully treated with valproate and L-thyroxine. The contribution of aging, hypothyroidism and stroke to the etiology of this woman's disorder is discussed. The pharmacological management of rapid cycling bipolar disorder in the elderly is also reviewed. PMID- 8348472 TI - [Elements for understanding "schizophrenic vulnerability"]. AB - Studies of the negative symptoms of schizophrenia seem to be of interest. However, the description of these symptoms is problematic. Some cognitive tests seem able to establish data that can be used to help discriminate among schizophrenic syndromes and to understand their different pathophysiology. Some of the main tests are described. Remarks concerning their value and the conditions of their interpretations are made. PMID- 8348473 TI - Clinical electroencephalography in a psychiatric service. AB - An audit of the use of clinical electroencephalography in a psychiatric service was carried out by examining the referrals for an EEG from the service over one year (11% of all referrals), comparing them with matched patient controls, rating the EEGs blindly and estimating the clinical value of the investigation for each patient; 37% were abnormal, 19% anomalous and 44% normal. The following two clusters of symptoms and signs were associated with EEG referral--the patients with "organic" mental state phenomena and/or CNS signs; EEG usually abnormal and the patients with behavioural changes that raise the suspicion of an organic process but, taken alone, are not compelling evidence of such (for example, impulsive behaviour, acute and atypical psychoses, perceptual or behavioural phenomena of the type associated with temporal lobe epilepsy in the absence of frank complex partial seizures); EEG usually normal or anomalous. Ninety-two percent of EEGs were judged to be of clinical value; 53% positive and 39% negative. Eight percent of referrals made no contribution to the clinical evaluation. PMID- 8348474 TI - [Psychological distress in a noninstitutionalized population of Quebec: normative results of the Quebec health survey]. PMID- 8348475 TI - The teaching of case formulation in Canada. AB - Prompted by the Council on Education and Professional Liaison of the Canadian Psychiatric Association, the authors surveyed the program directors and senior residents of departments of psychiatry on the teaching of case formulation skills in Canada. The results showed that case formulation is taught formally in most departments and that students are expected to demonstrate these skills throughout their training. However, less than one-half of the teaching programs provide guidelines for case formulation. The residents, who expected case formulation skills to be assessed in the oral examinations of the Royal College, were unanimous in their view that the process should be standardized and that guidelines be provided. Both the program directors and the residents favoured a biopsychosocial format for recording case formulation, but they did not agree on the content of an ideal formulation. PMID- 8348476 TI - Formulation: a multiperspective model. AB - This paper presents a model of formulation that can be used by psychiatrists and other mental health professionals. A review of the literature indicates a need for a more comprehensive approach that can accommodate a variety of perspectives, suggest treatment and can be easily recalled. These issues are addressed by the multiperspective grid presented in this paper. PMID- 8348477 TI - Teaching biopsychosocial integration and formulation. AB - This paper describes the mental processes by which the psychiatrist organizes and integrates data to produce a case formulation. The biopsychosocial formulation uses three perspectives (biological, psychological and social) to view the data and integrates these viewpoints into one broad, complex and dynamic appreciation of the patient. Guidelines for creating and communicating a case formulation are proposed. PMID- 8348478 TI - Alcohol abuse and schizophrenia. PMID- 8348479 TI - Depression and patients with rheumatoid arthritis. PMID- 8348480 TI - Emergency psychiatric consultation to a children's aid society. PMID- 8348481 TI - Is borderline personality disorder a post-traumatic stress disorder of early childhood? PMID- 8348482 TI - Syndrome of exchanged doubles. PMID- 8348483 TI - CT scan failure to confirm Pick's disease: a case report of "pseudo pseudodementia". PMID- 8348484 TI - The palpable breast nodule: a cost-effectiveness analysis of alternate diagnostic approaches. The role of the needle aspiration biopsy. PMID- 8348485 TI - CDw75 antigen expression in human gastric carcinoma and adjacent mucosa. AB - BACKGROUND: The amount of sialic acid correlates with the invasiveness and metastasizing potential of several human tumors. The CDw75 epitope is a sialylated carbohydrate determinant generated by the beta-galactosyl alpha 2,6 sialyltransferase, which can be viewed as a target for identifying biologically aggressive tumors. METHODS: The authors performed an immunohistochemical study of CDw75 epitope expression in 87 cases of gastric carcinoma and adjacent mucosa and 331 metastases (329 lymph node metastases and 2 liver metastases) with the monoclonal antibody HH2. RESULTS: Normal-appearing mucosa, foci of intestinal metaplasia, and foveolar hyperplasia, adjacent to the carcinomas, were mainly nonimmunoreactive. Only a few parietal cells of the body mucosa were stained with HH2. Two of 12 cases with dysplasia showed CDw75 antigen expression in dysplastic glands. Forty-one cases (47.1%) were immunoreactive for CDw75 antigen in the primary tumors or metastases. A very close relationship was found between the expression of the antigen in primary tumors and their respective metastases. The expression of the antigen was correlated with an infiltrative growth pattern, lymphatic invasiveness, and aneuploidy. All but two immunoreactive cases had lymph node metastases or lymphatic permeation. No relationship was found between CDw75 antigen expression and the morphologic types of gastric carcinoma, amount of lymphoid infiltrate, vascular invasion, and penetration of the gastric wall. CONCLUSIONS: The authors conclude that CDw75 antigen expression can be used as a marker of malignant transformation of gastric epithelium and is a good indicator of the biologic aggressiveness of gastric carcinoma. PMID- 8348486 TI - X-linked agammaglobulinemia and gastric adenocarcinoma. AB - BACKGROUND: The incidence and mortality rate for cancer in patients with primary immunodeficiency diseases have increased greatly. Lymphomas constitute more than 50% of tumors identified in the Immunodeficiency Cancer Registry, but solid tumors are frequent in these patients, especially gastric carcinomas. In addition to immunologic impairment, other local conditions such as chronic atrophic gastritis with intestinal metaplasia and pernicious anemia, usually observed in these patients, may play an important role in the genesis of gastrointestinal tumors. METHODS AND RESULTS: This report describes a 23-year-old patient with X linked agammaglobulinemia who had previously documented chronic atrophic gastritis with intestinal metaplasia, pernicious anemia, and parasitization with Giardia lamblia in whom an adenocarcinoma of the stomach developed. CONCLUSION: The authors believe that it may be useful to perform a periodic gastrointestinal evaluation for all patients with primary immunodeficiencies to establish early detection and treatment of these tumors. PMID- 8348487 TI - Clinical significance of dysplasia in gastric remnant biopsy specimens. AB - BACKGROUND: Dysplasia often is found in biopsy specimens from the gastric stump some 20 years after ulcer surgery. A high frequency of patients with severe dysplasia in the nonoperated stomach develop carcinoma but the clinical significance of dysplasia in the gastric stump is still confounding. METHODS: In the current study, two groups of patients were evaluated. One group of 22 patients, found at the first investigation in an endoscopic screening study with moderate dysplasia in the gastric stump, were regularly followed up to 18 years with endoscopy and biopsies. In the second part of the investigation, the authors evaluated 17 patients from the same endoscopic screening study, who at any instance during the 18 years were found to have severe dysplasia in biopsy specimens from the gastric remnant. RESULTS: In three of the 22 patients with moderate dysplasia, stump carcinoma was diagnosed 2, 2, and 6 years, respectively, after the first endoscopic examination. Severe dysplasia was found in two other patients at one occasion but later investigations only revealed moderate dysplasia. The remainder of the patients in this group had either persisting moderate dysplasia or mild dysplasia at follow-up. Seven (41%) of the 17 patients with severe dysplasia had stump carcinoma within a median time of 2 years (range, 1-11). Two other patients had surgery based on suspicion of carcinoma, but had only severe dysplasia in the surgical specimen. Finally, three men died (after 1, 2, and 17 years, respectively) of unrelated disease without suspicion of stump carcinoma and five patients were followed between 6 and 18 years without signs of malignant development. CONCLUSIONS: Patients with moderate and, especially, severe dysplasia in the gastric remnant are at high risk for gastric carcinoma. Severe dysplasia calls for endoscopic surveillance at short intervals. For patients with moderate dysplasia a close surveillance for 2 years followed by biannual evaluation appears sufficient. PMID- 8348488 TI - Clinicopathologically diagnosed residual tumor after resection for colorectal cancer. A 20-year prospective study. AB - BACKGROUND: A lack of comprehensive information exists on the nature, incidence, and prognostic significance of known residual tumor in colorectal cancer patients treated by bowel resection. This study aims to provide this information. METHODS: A prospective series of 1766 consecutive patients from the Concord Hospital Colorectal Cancer Registry (Concord, Australia) was used for the analysis. Residual tumor was defined as distant metastases diagnosed clinically or pathologically or tumor demonstrated histologically in a line of resection. The pathologic study was highly standardized. Patient follow-up ranged from 6 months to 20.5 years. Survival analysis was by the Kaplan-Meier method. Multivariate models were examined using Cox proportional hazards regression. RESULTS: The prevalence of residual tumor was 20.9% and the median survival was 11.6 months. In 4.5%, tumor transection alone occurred, 14.5% had distant metastases alone, and 1.9% had both. The difference in survival between the first two groups was at marginal statistical significance (P = 0.076). When each of these two groups was compared with the third group, significant differences were noticed (P = 0.001 and P = 0.004, respectively). Five of 14 pathology variables examined had a significant effect on survival using univariate analysis. On multivariate analysis only tumor transection and distant metastases had significant independent effects. CONCLUSIONS: Known residual tumor was common in this series: one in five resections. Survival studies show that tumor transection, as defined, is a valid criterion for residual tumor. Survival is significantly reduced when tumor transection and distant metastases both are present. These findings should be heeded when staging colorectal cancer and when stratifying patients for postoperative adjuvant therapy. PMID- 8348489 TI - Bowel rest, intravenous hydration, and continuous high-dose infusion of octreotide acetate for the treatment of chemotherapy-induced diarrhea in patients with colorectal carcinoma. AB - BACKGROUND: A prospective trial was conducted involving 16 patients with colorectal adenocarcinoma using a regimen of continuous-infusion octreotide acetate (Sandostatin [octreotide acetate], Sandoz, East Hanover, NJ for the treatment of severe diarrhea induced by the weekly schedule of 5-fluorouracil (5 FU) in combination with leucovorin who were refractory to opiate therapy. METHODS: Fifteen patients had tissue-documented metastatic colorectal adenocarcinoma. An additional patient was treated adjuvantly. Fifteen patients were treated with chemotherapy consisting of 5-FU and high-dose leucovorin. The octreotide acetate regimen used was a continuous infusion of 50 micrograms/h for 12 hours followed by 100 micrograms/h for 12 hours and subsequently 150 micrograms/h for 72 hours. All patients were previous failures of diphenoxylate atropine (Lomotil diphenoxalate], Searle, Chicago, IL) given 2.5 mg orally after each loose bowel movement, but no more than 20 mg in a 24-hour period. Opiate therapy was not continued beyond 48 hours. All patients also were treated with bowel rest (nothing by mouth) and intravenous fluid hydration as well as octreotide acetate. RESULTS: Complete resolution of diarrhea was seen in 15 of 16 patients (94%). In 4 patients this was accomplished during the 100 micrograms/h infusion, and in 11 patients during the 150 micrograms/h infusion. Recurrence of diarrhea was seen in two patients after a complete cycle of octreotide acetate. Both patients were restarted at 150 micrograms/h for 72 hours of octreotide acetate with resolution of the diarrhea within 36 hours of the infusion. No toxicity related to octreotide acetate was seen in this trial. CONCLUSION: The continuous-infusion regimen of octreotide acetate 150 micrograms/h is an effective and safe schedule for the treatment of chemotherapy-induced diarrhea together with bowel rest and intravenous fluid hydration in a group of patients in whom the majority were treated with the weekly schedule of 5-FU and high-dose leucovorin. PMID- 8348490 TI - Hepatic gastrinoma. AB - A solitary hepatic tumor in a 50-year-old woman, which was observed as a hemangioma, ultimately was resected because it increased in size. The tumor volume doubling time was 28.8 months over the observed period of 30 months. The histologic diagnosis was carcinoid tumor. Immunohistochemical staining showed strong focal reactivity for gastrin and diffuse reactivity for pancreatic polypeptide, vasointestinal polypeptide, calcitonin, and parathormone. Preoperative gastric hyperacidity with diarrhea and a body weight loss of 7 kg, moderately controlled by cimetidine on admission, suggested high serum gastrin levels produced by the tumor. Her symptoms resolved after surgery, and she had a normal serum gastrin level with negative secretin stimulation test results. A review of six cases of hepatic gastrinoma suggests that surgical resection, if feasible, would be the treatment of choice. PMID- 8348491 TI - Effect of age on survival in acute leukemia. 1950-1990. AB - BACKGROUND: Four decades ago, survival of patients with acute leukemia was brief at any age. Since 1950, survival of children has increased remarkably but has changed little for the elderly. The nature and magnitude of this age difference in survival are not understood. METHODS: Median survival was determined in 2364 Kansas residents diagnosed with acute leukemia from 1947 until 1990. Of this number, 1032 had acute lymphocytic leukemia and 1227 had acute myelocytic leukemia diagnosed between 1950 and 1989. These patients were stratified by age and decade of diagnosis. Survival was computed by life-table analysis with significance determined by log-rank, Wilcoxon, and Fisher exact tests. RESULTS: During the 40 years of the study, highly significant increases occurred in median survivals for all groups with either acute lymphocytic leukemia or acute myelocytic leukemia occurring in patients younger than 60 years of age (P < 0.0001 for some age groups), but no significant increases for those 61 to 80 years of age and those 81 years of age and older. Viewed in another dimension, for each decade from the 1960s to the present in acute lymphocytic leukemia and from the 1970s to the present in acute myelocytic leukemia, age at diagnosis was inversely correlated with median survival in a highly significant manner (P < 0.001). CONCLUSIONS: Increasing age is inversely related to survival in patients with acute leukemia. The lack of significant improvement in median survival in the last 40 years for those older than 60 years of age stands in stark contrast to the remarkable improvement for younger patients. Acute leukemia in older patients demands new and probably different therapeutic strategies. PMID- 8348492 TI - A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. AB - BACKGROUND: Few longitudinal studies have investigated the onset, duration, and resolution of ulcerative mucositis in bone marrow transplant recipients. This study prospectively followed a group of such patients on a daily basis to obtain data on the incidence of ulcerative mucositis, location and duration of lesions, severity with different conditioning regimens, and the relationship of such mucositis to the absolute neutrophil count. METHODS: Fifty-nine bone marrow transplant recipients on prophylactic acyclovir were examined daily for 26 days after marrow infusion, and all oral ulcerative lesions were recorded. RESULTS: Oral ulcers occurred in 76.3% of patients, began at a mean of 5 days after marrow infusion (day + 5), and lasted for a median of 6 days. More than 90% of patients showed complete resolution of ulcers on or before day + 15, and all showed resolution when the absolute neutrophil count was > 500 cells/ml. Persistence of ulcers was noticed in patients who had oral graft-versus-host disease and in some patients who initially developed more severe ulcerations. Ninety-six percent of ulcers were located on nonkeratinized mucosa. CONCLUSIONS: Ulcerative mucositis occurs in about 75% of bone marrow transplant recipients in the absence of herpes simplex virus infection. Most lesions occur on nonkeratinized mucosae which are vulnerable to trauma, especially if such mucosae are rendered atrophic by conditioning regimens. Oral ulcers may persist beyond day + 15 and after recovery of the neutrophil count in patients who initially develop more severe ulcerations or in patients who develop graft-versus-host disease. PMID- 8348493 TI - Giant basal cell carcinoma (T3). Who is at risk? AB - BACKGROUND: Giant basal cell carcinomas can cause extensive local invasion and disfigurement. This study determines in whom giant basal cell carcinomas develop. METHODS: Fifty patients with giant basal cell carcinomas (over 5 cm, T3) were compared with other groups of patients with small (< 2 cm, T1) or intermediate sized (2-5 cm, T2) basal cell carcinomas. The patients were treated at the Mayo Clinic between August 1986 and December 1990. RESULTS: Characteristics that were more common in giant basal cell carcinomas than in smaller lesions were duration, patient neglect, recurrence after previous treatment, aggressive histologic pattern, and history of radiation exposure. CONCLUSIONS: Patients who have a basal cell carcinoma with an aggressive histologic subtype, a recurrence after previous treatment, a history of radiation exposure, or a history of neglect are at risk for giant basal cell carcinoma. PMID- 8348494 TI - Evaluation of computed tomography in patients with peritoneal carcinomatosis. AB - BACKGROUND: Radiologic tests to determine the size and location of cancer on peritoneal surfaces are needed for patient management and for clinical research activity. METHODS: Computed tomography (CT) of the abdomen and pelvis were obtained on 45 patients with a diagnosis of peritoneal carcinomatosis before implementation of a complete exploratory laparotomy with biopsy or resection of all tissues suspicious of malignancy. CT findings and surgical findings were recorded and the data analyzed by dividing the abdomen into 9 regions or into 15 anatomic sites. RESULTS: In an overall patient analysis, the sensitivity was 79%. In the nine different abdominal regions, sensitivity was greater than 80% in the right flank, left flank, and right lower and left lower abdominal regions. Sensitivity was lowest in the pelvis (60%). Negative predictive value in the pelvis was 20%. The volume of tumor present within an abdominal region or anatomic site greatly influenced the sensitivity. A sensitivity of only 28% was recorded when tumor nodules were less than 0.5 cm in thickness. This increased to 90% when nodule thickness was greater than 5 cm. CONCLUSIONS: CT is not a reliable diagnostic test for low volume tumor on peritoneal surfaces, and the greatest inaccuracies were recorded in the pelvis. Its diagnostic value increased as tumor volume increased. PMID- 8348495 TI - Desmoid tumors of the trunk and extremity. AB - BACKGROUND: Twenty-six patients with desmoid tumors of the extremities (n = 20) or trunk (n = 6) have been treated since 1977. Nine of these were referred with primary tumors and 17 with recurrent tumors. METHODS: The tumor was removed in all patients, and 10 received adjuvant radiation. Five patients (19%) developed local recurrence; one of them was lost to follow-up, and the remaining four patients had the recurrence controlled with surgical resection or resection plus adjuvant radiation. RESULTS: All 25 patients who have been followed are alive and disease-free at a mean follow-up of 84 months (median, 81 months). None with extremity tumors (n = 20) required an amputation. The estimated survival rate for the entire group is 95% at 42 months. CONCLUSIONS: Desmoid tumor of the trunk or extremities treated with surgical resection, supplemented selectively by adjuvant radiation, can be controlled locally in the majority (96%) of patients. PMID- 8348496 TI - The palpable breast nodule. A cost-effectiveness analysis of alternate diagnostic approaches. AB - BACKGROUND: Traditionally, open biopsy has been considered the optimal procedure for the diagnosis of breast nodules. Fine-needle aspiration biopsy (FNAB) has been proposed as an alternate method for the diagnosis of many palpable breast lesions. METHODS: The authors compared the diagnostic utility of open biopsy and FNAB using decision tree and cost-effectiveness analyses. RESULTS: When compared with two-step excisional biopsy, FNAB achieved a savings of over $700 at the cost of 0.1% decrease in 10-year overall survival. CONCLUSIONS: These data indicate FNAB to be a reasonable alternative to open biopsy for the diagnosis of palpable breast lesions in many patients. PMID- 8348497 TI - Proliferative and nonproliferative breast disease in atomic bomb survivors. Results of a histopathologic review of autopsy breast tissue. AB - BACKGROUND: The risk of female breast cancer in association with radiation dose is well established, on the basis of follow-up studies of the atomic bomb survivors and other exposed populations. This association is especially strong for women exposed before 20 years of age and appears to be much weaker among women exposed after 40 years of age. METHODS: Breast tissue samples from 88 high dose and 225 low-dose autopsy cases from the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative and proliferative breast lesions are associated with radiation dose. RESULTS: Prevalence of proliferative disease in general and atypical hyperplasia in particular were positively associated with radiation dose. The associations were strongest for subjects who were between 40 and 49 years of age at the time of the bombing. CONCLUSIONS: It is hypothesized that the strongest association in women 40 to 49 years of age may be related to the age dependence of radiation-induced breast cancer, in that potential cancers induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers. PMID- 8348498 TI - Role of male behavior in cervical carcinogenesis among women with one lifetime sexual partner. AB - BACKGROUND: The role of male behavior in the genesis of cervical cancer was examined. In India, where the incidence of cervical cancer is among the highest in the world, promiscuity among women is virtually unknown. In this study, the authors investigated the role of male behavior in cervical carcinogenesis among Indian women who had one lifetime sexual partner. METHODS: A case-control study was used. RESULTS: Premarital sexual relationships (relative risk [RR], 1.9; confidence interval, 1.2-3.2) and extramarital sexual relationships (RR, 2.7; confidence interval, 1.5-4.9) of husbands were risk factors. When husbands had sexual relationships both before and during the marriage, their wives' risk of getting cervical cancer increased by 6.9 (CI, 2.3-20.7). Risk also increased with husbands having three or more extramarital sexual partners (RR, 3.05; CI, 1.25 12.6). Sexual contact with prostitutes before or after marriage, however, did not increase the risk. History of sexually transmitted disease before marriage (RR, 2.9) or after marriage (RR, 5.9) was an important risk factor, which persisted after controlling for other factors. Sexual abstinence for 40 or more days after a wife's giving birth or having an abortion provided protection. Sex with uncircumcised men or men circumcised after age 1 year increased the risk of cervical cancer (RR, 4.1). Bidi smoking (bidi is a cheap smoking stick of 4-8 cm, consisting of a rolled piece of dried temburni leaf [Diospyres melanoxylon] containing 0.15-0.25 g of coarsely ground tobacco) for more than 20 years was a significant risk factor (RR = 2.4), whereas cigarette smoking was not a risk factor. CONCLUSIONS: Male sexual partners play a role in cervical carcinogenesis. PMID- 8348499 TI - Plasminogen activator inhibitors in endometrial adenocarcinoma. AB - BACKGROUND: Plasminogen activators (PA) play an important role in the mediation of pathologic processes, including cancer invasion. Levels of urokinase are increased in malignant endometrium compared with normal endometrium. The role of PA inhibitors (PAI) in the malignant process is not known. METHODS: PAI-1 (endothelial type inhibitor) and PAI-2 (placental type inhibitor) in extracts of malignant (n = 14) and normal (n = 7) postmenopausal endometrium were measured. The results were correlated with the standard prognostic variables in endometrial carcinoma, namely, stage, histologic grade, depth of myometrial invasion, and estrogen receptor status of the tumor. RESULTS: PAI-1 was not detectable in normal endometrium and was present in small quantitities (0.11-1.54 ng PAI-1/mg protein) in 4 of 14 specimens of malignant endometrium. PAI-2 was present in 4 of 7 normal and all (14 of 14) malignant endometrial cytosols. PAI-2 levels were higher in Stage II and III compared with Stage I cancers (P < 0.05) and in malignant endometrium that invaded the myometrium to more than half its depth compared with those with less than 50% invasion (P < 0.05). No significant correlation was found between PAI-2 and estrogen receptor levels (r = -0.32). CONCLUSIONS: Endometrial adenocarcinoma has higher levels of PAI-2 than does normal postmenopausal endometrium. Highest levels of PAI-2 were found in the poorer prognostic categories of endometrial cancer. PMID- 8348500 TI - Prostatic acid phosphatase in strumal carcinoids of the ovary. An immunohistochemical study. AB - BACKGROUND: Strumal carcinoids (SC) are ovarian tumors containing thyroid parenchyma admixed with carcinoid elements. Microscopically, the carcinoid component of SC usually presents a ribbon or trabecular pattern similar to the pattern exhibited by hindgut carcinoids. The authors designed an immunohistochemical study to ascertain further similarities of the carcinoid component of SC to rectal carcinoids. METHODS: Five cases of SC were examined by light microscopic study with hematoxylin and eosin and immunoperoxidase staining with a group of neurohormonal peptides, thyroglobulin, prostatic acid phosphatase, and prostate specific antigen. RESULTS: All tumors were positive for thyroglobulin, chromogranin, prostatic acid phosphatase (PAP), and glucagon. They were consistently negative for prostate specific antigen and variably positive to the other antibodies. CONCLUSIONS: The consistent positivity of the carcinoid component of SC to PAP immunostaining is a further similarity of these tumors to rectal carcinoids, in which positive immunostaining to PAP has been observed. The similarity is not well understood, however, as all evidence points to the origin of SC from germ cells in mature cystic teratomas without any embryologic relationship to the hindgut. PMID- 8348501 TI - Organization of type III collagen in benign and malignant ovarian tumors. An immunohistochemical study. AB - BACKGROUND: Abnormal interaction with the extracellular matrix is a basic property of malignant cells. Type III collagen is a major constituent of the extracellular matrix of soft tissues. METHODS: Deposition of the aminoterminal propeptide of type III procollagen (PIIINP) was studied in benign (n = 41), borderline (n = 4), and malignant (n = 32) human ovarian tumors using the avidin biotin-immunoperoxidase technique and affinity-purified antibodies to human PIIINP: It was then compared with the serum PIIINP concentrations of the patients at the time of operation. RESULTS: In malignant tumors, the distribution of PIIINP was irregular both close to the epithelial cancer cells and further away, in the stroma. Another feature typical of malignant tumors was the varying staining intensity of the PIIINP-positive fibers. The benign tumors were characterized by a regular organization and an intensive staining of PIIINP: Borderline tumors showed a slightly decreased staining intensity and altered PIIINP distribution. A significant positive correlation was found between the PIIINP concentration in serum and the degree of irregularity in the distribution of PIIINP: CONCLUSIONS: These preliminary results indicate that malignant transformation in ovarian tumors is associated with disintegration of adjacent collagenous structures and with alterations in type III procollagen metabolism, which also leads to increased serum PIIINP levels. They suggest that biochemical or immunohistochemical detection of the PIIINP antigen could be clinically useful in ovarian tumors. PMID- 8348502 TI - Daily alternating administration of high-dose alpha-2b-interferon and interleukin 2 bolus infusion in metastatic renal cell cancer. A phase II study. AB - BACKGROUND: Both interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) have some efficacy in renal cell cancer (RCC) as single agents. Additionally, there is some evidence for additive or synergistic antitumoral activity of IL-2 and alpha-IFN in vitro and possibly in vivo. Based on these data, the authors initiated a Phase II trial with a combination of recombinant IL-2 (rIL-2) and recombinant alpha-IFN (alpha-rIFN) in advanced RCC. METHODS: Thirty-six assessable patients with metastatic RCC were entered in this Phase II trial using a daily alternating schedule of alpha-rIFN and rIL-2. Over a period of 14 days, the patients received daily alternating treatment with 10 x 10(6) IU/m2 of recombinant alpha-2b interferon subcutaneously and 18 x 10(6) IU/m2 of rIL-2 as a 1-hour intravenous infusion. This treatment schedule was repeated every sixth week up to a maximum of four cycles. After the second cycle, patients were examined for response. Patients with stable disease or better received two additional cycles of therapy. Patients with progressive disease were available for other strategies. RESULTS: Thirty-six patients entered the trial and were assessable for toxic effects. Thirty of 36 patients completed at least two cycles and were assessable for response. Nine patients achieved an objective response: 2 had complete responses (CR) and 7 had partial responses (PR). Three patients had a minor response. No effect was observed in patients with local relapse or bone metastases. A relapse free survival length of 6 months or longer was seen in both patients with CR (12, 23 + months) and in four of seven patients with PR (6, 7, 12, 12 months). The toxicity was moderate and included fever and nausea in most patients, and hypotension, fatigue, skin rash, and arthralgia in a minority of the patients. No Grade 4 and only occasionally Grade 3 toxicity was observed. Fluid retention was negligible. The monitoring of immunologic parameters showed a significant rebound lymphocytosis including cytotoxic (CD56+) cells; in responders the peak of lymphocytosis occurred up to 1 week later than in nonresponders. Peripheral lymphocytes obtained after therapy showed only a slight increase of natural killer cell and lymphokine-activated killer cell activity. During therapy, there was a great release of secondary cytokines as tumor necrosis factor-alpha, gamma interferon, and interleukin-6, with a peak level 2-4 hours after rIL-2 infusion. CONCLUSIONS: In conclusion, daily alternating administration of alpha-rIFN and rIL-2 is effective in RCC with less toxicity, and the response rate is comparable to those of other immunotherapeutic schedules, including adoptive immunotherapeutic schedules, including adoptive immunotherapy and combinations of high-dose IL-2 and alpha-IFN. PMID- 8348503 TI - Interferon-alpha-2b enhances the natural killer activity of patients with transitional cell carcinoma of the bladder. AB - BACKGROUND: Transitional cell carcinoma (TCC) of the bladder is associated with alterations in the immune system of the host. The authors demonstrated that in patients with bladder carcinoma there is a negative correlation between the levels of natural killer (NK) activity and the clinical evolution and pathologic stages of disease. METHODS: The authors investigated the effect of various doses of recombinant interferon-alpha-2b (IFN-alpha-2b) for variable periods of culture on the nonmajor histocompatibility-restricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) with or without CD16 and CD3-depleted populations from patients with superficial (confined to the mucosa or lamina propria) and infiltrative (those infiltrating beyond the lamina propria) TCC of the bladder using 4-hour 51-sodium chromate (51Cr)-release cytotoxicity assays against both NK-sensitive (K562) and NK-resistant (JY) tumor target cells. RESULTS: The normal NK activity detected in PBMNC from patients with superficial TCC of the bladder can be significantly enhanced by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). The depressed NK cytotoxic activity found in PBMNC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). Short-term recombinant IFN-alpha-incubated PBMNC from patients with superficial, but not infiltrative, TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. By selection with CD16 or CD3 monoclonal antibodies and complement, it was also found that the precursor and effector lymphocytes of this recombinant IFN-alpha-promoted cytotoxicity belong to NK lineage. In kinetic studies, it was found that the maximal levels of the recombinant IFN-alpha-promoted cytotoxic activity against NK-sensitive and NK resistant target cells in PBMNC from patients with TCC were reached after 18 hours of culture. CONCLUSION: Recombinant IFN-alpha can enhance the nonmajor histocompatibility-restricted cytotoxic activity of PBMNC from patients with TCC of the bladder. PMID- 8348504 TI - Intravesical 4'-epi-doxorubicin (epirubicin) versus bacillus Calmette-Guerin. A controlled prospective study on the prophylaxis of superficial bladder cancer. AB - BACKGROUND: The selection of the most appropriate antineoplastic agent and optimal treatment schedule for the prophylaxis of superficial bladder cancer against tumor recurrences is the subject of continual investigations. METHODS: A controlled prospective trial involving 161 patients evaluated and compared the efficacy of intravesical epirubicin and bacillus Calmette-Guerin (BCG) administration as prophylaxis against recurrences after complete transurethral resection of superficial bladder cancer. The treatment schedule, consisting of one 6- or 8-week course of instillations (50 mg epirubicin or 150 mg BCG per instillation) followed by single maintenance doses to the responders at follow-up examinations, was modified for those of the initial responders who were at high risk for recurrence and who received an additional separate 4-week course of treatment 6 months after the start of therapy. RESULTS: Sixty percent of the patients treated with epirubicin, 68% of the patients treated with BCG, and 41% of the control subjects, who underwent resection only, remained free of recurrences for a mean follow-up of 32.9 months. The only significant difference was found between patients treated with BCG and control subjects, in favor of the former. Conversely, recurrence rate per 100 patient-months and mean interval to recurrence showed both drugs to be superior to resection alone regarding several tumor characteristics. However, a significant benefit in favor of BCG when compared with epirubicin was shown in those patients who had Stage T1 and Grade 3 tumors at presentation. CONCLUSIONS: Intravesical epirubicin and BCG were superior to transurethral resection alone in the prophylaxis of superficial bladder cancer, but with respect to superficially invasive and high-grade tumors, BCG demonstrated a remarkable advantage. PMID- 8348505 TI - Squamous carcinoma presenting as an enlarged cervical lymph node. AB - BACKGROUND: Patients presenting with an enlarged cervical lymph node containing squamous cell carcinoma are a difficult problem for head and neck surgeons. In most cases, the primary site lies in the head and neck region. The advent of fine needle aspiration cytologic study means that this group of patients can be accurately identified in the clinic and investigated accordingly. METHODS: The current report studies the records of 267 such patients presenting to the Head and Neck Unit at The University of Liverpool over a 29-year period. RESULTS: The 5-year survival rate for all patients presenting with a cervical lymph node metastasis was 27%. The 5-year survival rate for patients with a detected primary in the head and neck was 31% and the primary site was identified during the patient's life time in all but 36 patients (13%). In 53% of patients, the primary site was discovered during routine clinical examination, and in a further 16% it was discovered at panendoscopy. Most diagnostic tests proved relatively unhelpful but 10 patients in our series had the primary site discovered by radiograph and 9 of these had carcinoma of the lung. In the current study when the primary site was discovered it was in the head and neck region in 74% of patients. Primary sites other than head and neck occurred in 11% of the patients and no 5-year survivors existed. Multivariate analysis suggested that open biopsy of the lymph node metastasis appeared to have an adverse effect on survival as did advanced age and advanced N stage. The late diagnosis of the primary site, if it proved to be in the head and neck region, on the other hand, had a positive association with survival. CONCLUSIONS: Patients presenting with a lymph node metastasis in the head and neck region from an unknown primary have a prognosis identical to that of other patients with head and neck squamous carcinoma with neck node metastases. The prognosis for patients in whom the primary site is never discovered or in whom the primary site is not head and neck, however, is disastrous. If the primary tumor proves to be in the head and neck region, treatment is worthwhile since almost a third of patients are cured of their disease. When the primary carcinoma is not in the head and neck region, treatment must be considered palliative. PMID- 8348506 TI - Clinicopathologic study of 212 cases of peripheral T-cell lymphoma among the Japanese. AB - BACKGROUND: Postthymic/peripheral T-cell malignancy shows significant histopathologic and clinical diversity, even in its prognosis, and the correlations remain to be debated. METHODS: The clinicopathologic features of 212 Japanese patients with these neoplasms were investigated. RESULTS: There were 131 male and 81 female patients, whose ages ranged from 2 to 90 years (mean, 51.7 years). Lymphadenopathy was the most frequent clinical presentation, and the patients also had frequent skin lesions, hyperimmunoglobulinemia, hypercalcemia, and a rapid clinical course. Furthermore, the differences in the histologic features of each subcategory reflected the clinical pictures. The immunophenotypic analysis was indispensable in establishing a correct diagnosis, and the high-grade tumors often showed loss of pan-T antigens. CONCLUSIONS: The histopathologic classification proposed by Suchi et al., which has been incorporated into the updated Kiel classification, showed a good prognostic correlation. PMID- 8348507 TI - Some occupational exposures as risk factors for malignant lymphomas. AB - BACKGROUND: Malignant lymphomas (Hodgkin disease [HD] and non-Hodgkin lymphoma [NHL]) have been subject to several epidemiologic studies and found to be associated with various environmental exposures, especially solvents, wood, and phenoxy herbicides. METHODS: Various determinants for HD and NHL were evaluated in a case-referent study encompassing 31 cases of HD, 93 cases of NHL, and 204 referents, all alive. Information on these determinants, mainly occupational exposures, was obtained by mailed questionnaires. RESULTS: Crude odds ratios were increased for various occupational exposures, i.e., exposures to solvents, pesticides, metal fumes, welding, and fresh wood, and nursing. Further analyses based on logistic regression indicated exposure to phenoxy herbicides and fresh wood among sawmill workers, lumberjacks, and paper pulp workers to be significant risk factors for HD. Welding, working as a lumberjack, nursing, and ex-smoking were associated with a significantly increased risk for NHL. Radiographic examinations were negatively associated with HD, as was office work for NHL. CONCLUSIONS: The results were mainly in agreement with the findings of earlier studies, but diverging associations also appeared. PMID- 8348508 TI - The appearance of Kaposi sarcoma during corticosteroid therapy. AB - BACKGROUND: Four epidemiologic types of Kaposi sarcoma (KS) are known: classic KS, endemic African KS, epidemic or acquired immunodeficiency syndrome-related KS, and KS associated with immunosuppressive therapy. In most of the latter patients, KS was reported to have developed after organ transplantation, particularly renal transplantation. Thirty-nine patients who have not had a transplant have been reported to have KS associated with corticosteroid therapy. METHODS: The authors studied 10 patients with the appearance of KS during corticosteroid therapy (6 men, 4 women; age range, 42-79 years) who were treated with corticosteroids for autoimmune disorders (5 patients), lymphoproliferative disorders (2 patients), and diseases unrelated to the immune system (3 patients). RESULTS: Genetically programmed susceptibility to corticosteroid-related KS was suggested by the descent of the study patients as well as most of those reported previously. The prognosis was guarded in all the study patients. CONCLUSIONS: Corticosteroids should be withdrawn to achieve clinical remission. PMID- 8348509 TI - Primary Hodgkin disease of the ileum complicating Crohn disease. AB - BACKGROUND: Primary gastrointestinal lymphoma currently is considered to be an uncommon complication of chronic inflammatory bowel disease. All tumors reported in which recently developed techniques, such as immunohistochemical markers, were used for lymphoma classification proved to be non-Hodgkin lymphomas. Gastrointestinal lymphomas developing in Crohn disease are a very heterogeneous group, with tumors of both B-cell and T-cell lineage represented, along with some tumors of equivocal phenotype. By contrast, gastrointestinal lymphomas complicating ulcerative colitis all have proved to be so-called polymorphic B cell lymphomas. METHODS: The current report describes another case of primary gastrointestinal lymphoma complicating chronic inflammatory bowel disease occurring in the ileum of a 34-year-old man with a 3-year history of Crohn disease. RESULTS: Histopathologic findings were in keeping with nodular sclerosing Hodgkin disease. Broad birefringent collagen bands divided the tumor into well-defined nodules consisting of typical Reed-Sternberg cells and lacunar variants admixed with a polymorphous lymphoid infiltrate. By immunohistochemical studies, Reed-Sternberg cells and lacunar variants stained positively for Leu-M1 (CD15) and Ber H2 (CD30). The background lymphocytes were primarily of T-cell phenotype. CONCLUSIONS: To the knowledge of the authors, this article reports the first case of primary gastrointestinal Hodgkin disease in association with chronic inflammatory bowel disease that has been confirmed by immunohistochemical studies. PMID- 8348510 TI - Ifosfamide with mesna uroprotection and etoposide in recurrent, refractory acute leukemia in childhood. A Pediatric Oncology Group Study. AB - BACKGROUND: Ifosfamide has previously been shown to be active as a single agent and in combination with doxorubicin, etoposide, and teniposide in pediatric solid tumors and adult acute leukemia. The authors performed a dose-escalation trial of ifosfamide with a fixed dosage of etoposide, with mesna uroprotection, in children with multiply recurrent acute leukemia. METHODS: Chemotherapy was administered daily for 5 days. Etoposide 100 mg/m2 was followed by ifosfamide at an initial dosage of 1.6 g/m2. The ifosfamide was escalated in 20% increments to the maximum tolerated dosage in cohorts of three patients. Mesna 400 mg/m2 was given immediately before the ifosfamide and then at 3 and 6 hours after ifosfamide in the initial patients. Subsequent patients were treated with mesna 400 mg/m2 just before ifosfamide, and then every 2 hours to a total dosage equal to the ifosfamide dosage. RESULTS: Forty-four heavily pretreated patients were entered on study. Forty were evaluable for toxicity and 36 for response as well. The maximum tolerated dosage of ifosfamide was 4.0 g/m2/d for 5 days (20 g/m2/course). Overall, 10 patients achieved complete remission, and 3 achieved partial remission. Remissions were brief, although four patients went on to bone marrow transplant while in remission. One patient is still alive. CONCLUSIONS: The combination of etoposide and ifosfamide with mesna uroprotection showed promising activity in children with multiply recurrent acute leukemia. PMID- 8348511 TI - Response to neoadjuvant chemotherapy in children with pineoblastoma. AB - BACKGROUND: The outlook of children with pineoblastoma treated with radiation therapy alone is extremely poor, but neoadjuvant chemotherapy has been tried only in a few cases of this rare childhood brain tumor with poor prognosis. METHODS: Three consecutive children 3 to 7 years of age received neoadjuvant chemotherapy consisting of etoposide 100 mg/m2 days 1 to 3, cisplatin 100 mg/m2 day 1, and vincristine 1.5 mg/m2 day 1, repeated every 4 weeks. After four courses of chemotherapy, patients underwent craniospinal irradiation. The radiation doses to the primary site ranged from 5040 to 5440 cGy and craniospinal axis radiation dose was 2520 to 3060 cGy. RESULTS: After chemotherapy, mild myelosuppression occurred in all three and mild to moderate bilateral high-frequency sensorineural hearing loss occurred in two of the three patients. One patient remains in near complete resolution of the tumor at 2 years after diagnosis and another remains in CR for 5 years. One patient achieved PR for 5 months but eventually died of progressive tumor. CONCLUSIONS: This study suggests that the neoadjuvant chemotherapy as used here is effective and has acceptable toxicity. PMID- 8348514 TI - For sale! Nursing services. PMID- 8348512 TI - Testicular angiocentric lymphoma of postthymic T-cell type in a child with T-cell acute lymphoblastic leukemia in remission. AB - BACKGROUND: Angiocentric lymphoma developed in a 6.5-year-old boy with acute lymphoblastic leukemia of thymic origin in remission. He presented with unilateral testicular enlargement 17 months after diagnosis. METHODS AND RESULTS: Biopsy of the testis revealed an angiocentric, angiodestructive polymorphous cellular infiltrate accompanied by necrosis. The lymphoid component showed a mature T-cell immunophenotype (positive for CD2, CD3, CD5, CD7, CD4, CD8). CONCLUSIONS: Angiocentric lymphoma is a rare entity included in the spectrum of angiocentric immunoproliferative lesions, which preferentially involves extranodal sites. Although four cases of angiocentric immunoproliferative lesions have been reported in pediatric patients with acute lymphoblastic leukemia, this is the first reported occurrence of testicular involvement. PMID- 8348513 TI - Surgical lateral clearance in resected rectal carcinomas: a multivariate analysis of clinicopathologic features. PMID- 8348515 TI - Obstetrical triage. PMID- 8348516 TI - The birth of an alternative delivery centre. PMID- 8348517 TI - Sick and tired. PMID- 8348519 TI - Beyond comprehension. PMID- 8348518 TI - "It's not in my head". PMID- 8348520 TI - Growing up with violence. PMID- 8348521 TI - Evaluating the collaborative approach. PMID- 8348522 TI - [Removing a femoral catheter]. AB - Nurses at the University of Ottawa Heart Institute are removing femoral sheaths on post-angioplasty patients. The authors describe this new technique and explain how nurses can benefit by doing it. They discuss practical considerations before delegating this sanctioned medical act to nurses. Prevention and management of complications are also discussed as are research projects to evaluate the technique. PMID- 8348523 TI - [Female student of a visible minority]. AB - This article is the second on visible minority groups in schools of nursing and the profession. The survey was conducted in three institutions in the Ottawa region. The goal was to discover whether statistics reflect the current college and university nursing population. Of this population, 73.7 per cent participated. Results show clearly that the following questions must be answered by health professionals responsible for community services: Is the goal of equal representation of all ethnic groups at the college and university level realistic? How can educators identify reasons why certain ethnic groups lean toward nursing? Will it be necessary to consider several factors in order to clearly identify the visible minority representation? These questions and others will guide the authors in their subsequent surveys of minority representation in the health care professions. PMID- 8348524 TI - Pain management at home. Struggle, comfort, and mission. AB - This article presents findings from an exploratory, descriptive study that investigated the experiences of pain in the home from the perspective of the patient, the primary family caregiver, and the home care nurse. The following research questions are addressed: What are the special problems associated with pain management at home as identified by patients, caregivers, and nurses? What are the similarities and differences among patients, caregivers, and nurses regarding issues of managing pain at home? Qualitative techniques were used to collect and analyze data. The sample included 10 cancer patients with pain and their respective caregivers and nurses. After the in-depth interviews were transcribed, a multidisciplinary research team performed content analysis on the data. Overall, the findings suggest that patients approach pain management with a struggle for control, whereas self-denying caregivers seek to provide comfort, and nurses attempt to fulfill an urgent mission to eradicate pain. PMID- 8348525 TI - Experienced nurses' narratives of their being in ethically difficult care situations. The problem to act in accordance with one's ethical reasoning and feelings. AB - In previous interviews, experienced nurses have reported that their decisions in ethical matters depended "on the situation at hand." We interviewed 18 good, experienced cancer nurses to determine how they handled ethical decisions. They were asked to give an account of difficult situations that required ethical decisions to be made. The 60 narrated situations were interpreted step-by-step departing from the following two questions: What do nurses experience when being in ethically difficult care situations? What does the expression "it depends on the situation at hand how I act" mean? In complex situations, the nurses reported that the ethical situations that arose were regarded either as overwhelming or at the other end of the spectrum, as possible to grasp, and they expressed either loneliness or togetherness, respectively. When reporting overwhelming situations, the nurses mostly referred to themselves by using the word "one," i.e., "one would" and used "they" when referring to their coactors. When narrating situations possible to grasp, they used the terms "I" and "we." The most important situational factor that was revealed in these narratives was whether or not the nurses had a support group in which to share their thoughts. Without the support group, they reported difficulties acting in accordance with their ethical reasoning and feelings. PMID- 8348526 TI - Immunotherapy and neuropsychiatric toxicity. Nursing clinical management consideration. AB - Ensuring the safety of patients who receive immunotherapy is an essential element of nursing care. Communicating changes in mental status to the medical team is important feedback for modifying or discontinuing the cycle of immunotherapy. These observations are even more crucial if neuropsychiatric toxicity (NPT) has been exhibited in a previous cycle of treatment. If nurses are aware of associative factors of NPT they can be more alert for emerging cognitive dysfunction. Early intervention will also mean the nurse will take additional measures to ensure patient safety, such as suggesting possible pharmacological alternatives and closer observation, and encouraging family members to help with orientation. The nurse can further assist by helping alleviate the patient's or family's feelings of helplessness by assuring them that the NPT will begin to subside once treatment has been terminated. PMID- 8348527 TI - A comparison of American and Egyptian cancer patients' attitudes and unmet needs. AB - The purpose of this descriptive study was to compare and contrast similarities and differences in statements made by American and Egyptian cancer patients who expressed their attitudes toward cancer and reported their unmet needs. A total of 61 American and 66 Egyptian patients, who were receiving chemotherapy or radiotherapy, or a combination of the two treatments at the time of data collection, participated in the study. The American sample was drawn from patients at a large midwestern hospital, whereas the Egyptian sample was drawn from patients at the largest university hospital in Cairo, Egypt. Data were collected through a structured interview method in both patient populations. Analyses of responses showed five categories of attitudes for the American patients: (a) fighting spirit and adaptation, (b) fear/anxiety/disbelief, (c) hope, (d) passivity in plan of care, and (e) faith. For Egyptian patients, seven categories emerged: (a) stoicism and fatalism, (b) dependency, (c) compliance with the medical regimen, (d) anxiety/fear/insecurity, (e) powerlessness, (f) hope and optimism, and (g) family support. American cancer patients reported their unmet needs as (a) information, (b) needs related to treatment side effects, and (c) psychological support. Egyptian cancer patients reported their unmet needs as (a) relief from dependency, (b) relief from physical symptoms, and (c) information. These findings have implications for international oncology nursing, and imply the need for further research to determine if attitudes and unmet needs affect coping effectiveness and quality of life among cancer patients. PMID- 8348528 TI - Autologous bone marrow transplantation. A review of the principles and complications. AB - High-dose chemotherapy and autologous bone marrow transplantation (ABMT) is now used routinely in an attempt to cure patients with poor-prognosis malignant diseases. This aggressive and intensive treatment requires a highly trained health-care team. Nurses specializing in the care of these patients are essential to maintain patient well-being and ensure a good outcome. High-dose therapy leads to myelosuppression and tissue damage, and the resultant infections, bleeding, and organ toxicities are frequently either unusual or more severe than those seen with conventional-dose antineoplastic therapies. Organ toxicities can affect both short-term and long-term functional status. Disabling or even fatal consequences of treatment can occur during the transplant or months or years later. A specialized knowledge base and an understanding of the way this therapy affects the patient is required not only for the acute inpatient period, but also for the long term. A team approach to these complex patients with a central role for the nurse clinician will lead to optimal patient care. PMID- 8348529 TI - Oral- and pharyngeal-cancer patients' perceived symptoms and health. AB - The purpose of this study was to describe the perceived eating problems, general symptoms, and general health of a group of oral- and pharyngeal- cancer patients before surgery in order to facilitate nursing care planning. A total of 29 patients (20 men and nine women) participated. Two groups were formed: in group 1, 13 patients participated before and, in group 2, 16 patients participated after the presurgical radiotherapy. Questionnaires were used to collect data. Eating disabilities were evident in both groups. The patients who had had their radiation therapy experienced problems such as bad taste function, mouth dryness, difficulties in chewing, and mouth pain more frequently than those who had not been treated. Only five patients in group 2 ate solid food, compared with 10 in group 1. Shoulder and back pain and feelings of worry and anxiety were perceived as the most frequent general symptoms. Most of the patients perceived their general health as being rather good, but some indicated poor health, several symptoms, poor appetite, and/or severe eating problems. Patients with oral and pharyngeal cancer should be carefully assessed before surgery because of their disparity of symptoms and disabilities so as to identify those who need specific nursing interventions. PMID- 8348530 TI - Psychosocial and functional status of breast cancer patients. The influence of diagnosis and treatment choice. AB - This exploratory study examined breast cancer patients' psychosocial and functional status at the time of diagnosis and during the initial phase of treatment. The purpose was to better understand the impact of diagnosis and treatment on patients' physical state and psychosocial well-being. A convenience sample was drawn from a population of newly diagnosed stage 1 and 2 breast cancer patients undergoing either modified radical mastectomy or lumpectomy with radiation. Subjects completed instruments designed to measure uncertainty, quality of life, functional status, and reaction to diagnosis on two separate occasions: at the time of diagnosis, but before treatment selection and then approximately 8 weeks after surgery. Data obtained from 52 subjects indicated that patients' perceptual uncertainty and various aspects of their functional status declined over the initial course of treatment, but that quality of life was unaffected. The results also showed no relationship between type of breast cancer treatment and patients' uncertainty, quality of life, and functional status. Mastectomy and lumpectomy patients also responded in similar ways to the cancer diagnosis. Both groups experienced the same amount of distress and used conformational coping strategies to similar degrees. Clinical implications are discussed and recommendations are made for future research. PMID- 8348531 TI - Dependent care, caregiver burden, and self-care agency of spouse caregivers. AB - A convenience sample of 113 spouse caregivers was used to examine the relationships between dependent care, caregiver burden, and self-care agency. Subjects were the spouses of radiation oncology or chemotherapy patients in a large metropolitan hospital. The Denyes Self-Care Agency Instrument was used to measure self-care agency. The Task Scale was used to operationalize dependent care, and the Burden Scales were used to measure caregiver burden. Demographic data were collected on the number of weeks in the caregiver role, presence of health problems in the caregiver, gender, age, income, and education. In the total sample, subjective burden was negatively and significantly related to self care agency and objective burden, in addition, dependent care and objective burden were also negatively related. When the data were divided into subsamples based on gender, several of the relationships were in opposite directions. The most notable of these were the relationships between dependent care and self-care agency. It is evident that interventions should take these gender differences into account. PMID- 8348532 TI - The molecular pathology of cancer. Introduction. PMID- 8348533 TI - Models of pancreatic cancer. AB - Progress has been made in recent years in defining the spectrum of molecular changes seen in human pancreatic cancer. A range of animal models of this disease exists, and the nitrosamine induced tumours in the hamster show "clinical", morphological, immunophenotypic and, importantly, molecular similarities with human disease. This may prove to be an important model for testing therapeutic stratagems. In vitro systems for assessing pancreatic carcinogenesis and neoplasia are much less well developed. Although many human pancreatic primary carcinoma cell lines exist, it is difficult to culture normal human pancreatic cells effectively. Future studies will probably need to concentrate on the development of rodent systems (especially hamster), which can be more easily maintained. Studies in transgenic mouse systems have given new insights into the genesis of pancreatic neoplasia, and taken with those studies of acinar to ductal transdifferentiation, they cast new light on the possible origin of the tumour. This important issue remains unresolved, and its further understanding will require the generation of new data on the kinetic and spatial organization of the pancreas where key questions remain unanswered--whether there is a stem cell compartment in the organ not least among them. Progress in the cellular and molecular aspects of the disease are essential; so too are some important morphogenetic issues. PMID- 8348534 TI - In vitro models of human colorectal cancer. AB - Epithelial cell lines that differentiate in vitro have been isolated from hereditary and sporadic colorectal adenomas representing different stages in tumour progression, from small adenomas with a low malignant potential to large adenomas with a relatively high malignant potential. The majority of cell cultures derived from small adenomas senesced, whereas the larger adenomas were more likely to give rise to an immortal cell line. Karyotypic analysis has shown that specific abnormalities of chromosomes 1, 6, 7, 13, 14, 17, 18 and 22 occur in these adenoma cell lines. Abnormalities of chromosome 1 have been implicated in tumour progression and the in vitro immortalization of colorectal adenomas. Molecular and cellular changes involving abnormalities of chromosomes 1 and 18, TP53 and ras gene mutations and reduced response to the growth inhibitory effects of TGFB and sodium butyrate, which occur during tumour progression, suggest that the in vitro model has relevance to in vivo carcinogenesis. PMID- 8348535 TI - Molecular pathology of lymphomas. AB - Chromosomal translocations appear to be the initiating step in the development of malignancy in both B cell and T cell lymphomas. These results in the juxtapositioning of proto-oncogenes and transcriptional factors to the IG or TCR genes and lead to the deregulation of their expression. A survival advantage is provided to the lymphoid cells and contributes to neoplasm by permitting a clone to persist until other oncogenes such as c-myc are activated. This suggests a multistep progression to tumorigenesis. The occurrence of these translocations is assisted by obligatory DNA breaks and rearrangements of IG and TCR that have to occur for B and T cells to mature and function. The molecular alterations specific to lymphomas provide a potential specific target for therapy, including molecular manipulations. Animal modelling of lymphoma will provide the greatest possibilities for investigating the pathogenesis of lymphoma and future treatment modalities. PMID- 8348536 TI - Oncogenes, growth factors and control of the cell cycle. AB - Recent advances in the field of cell cycle progression have extended our knowledge of the mechanism(s) of cellular proliferation and have placed it on a solid molecular basis. This survey highlights some of these findings, selecting the most intriguing in the hope of providing new insights on cell cycle controls. We have considered two large groups of factors involved in cell cycle control: extracellular (environmental signals, ie growth factors, and their cellular receptors) and intracellular (oncogenes and anti-oncogenes), indicating which, to us, may be the most promising areas of investigation. These include the events occurring after the IGF1 receptor is activated by its ligand, the role of anti oncogenes in preventing the activation of growth factor receptors, the mechanism(s) by which some proto-oncogenes may short circuit the cell cycle and the use of peptide analogues and the antisense strategy to study and to regulate cellular proliferation. PMID- 8348537 TI - Models of colorectal tumour differentiation. AB - In vitro models in which colorectal tumour cells express differentiated and undifferentiated phenotypes have been developed and used to identify the molecular mechanisms of cellular and morphological differentiation of colorectal epithelial cells. Our data indicate that both cell-cell and cell-collagen interactions are required for the induction and maintenance of the glandular differentiation of colon carcinoma cell lines in vitro. These interactions are primarily mediated by two classes of adhesion molecules, E-cadherin and alpha 2/beta 1 integrin. Both cell surface adhesion receptors are lost in poorly differentiated colorectal tumours, and these changes may explain in part the phenotype and behaviour in vivo. Further investigation of the molecular control of integrin and cadherin function, localization and level of cell surface expression will constitute the basis of new functional assessment of tumour differentiation and likely response to treatment in colorectal cancer. PMID- 8348538 TI - The molecular pathology of human breast cancer. AB - Perhaps one of the most exciting recent developments in breast cancer research is the steadily increasing number of small screen detected lesions which are available for study. These samples will allow a number of questions of key importance to the development and progression of breast cancer to be answered. For example, the relationship between a variety of benign and premalignant lesions and frankly invasive breast carcinomas can be examined to determine the sequence of progression, if indeed such a sequence exists. Subtypes of screen detected lesions may be identified in which different genetic events have occurred, and the relationship between these genetic events and progression may be established. Such studies could identify groups of women for whom no further treatment is required or those for whom adjuvant therapy, radiotherapy or further surgery is indicated. A number of genetic alterations have now been identified that seem to be independent indicators of prognosis. Such alterations include overexpression of c-erbB2 and mutation of TP53. Although there is still some debate about the statistical significance of data from a number of different groups, it seems certain that the status of a number of genes will provide prognostic information to augment existing criteria. There is an urgent need for an examination of a large panel of breast tumours for a number of key genetic alterations and for a critical evaluation of all the changes to existing clinical variables such as clinical stage, grade, survival and relapse times and growth factor receptors. Molecular pathology is providing new and exciting insights into the pathogenesis of human breast cancer, and molecular events associated with inherited breast disease, early stages, progression and metastasis of breast cancer are now becoming better understood. PMID- 8348539 TI - Human models of breast cancer. AB - Experimental systems using human mammary tissue, secretions and tumours may be based on in vitro culture or on growth of tissue or tumour fragments in the nude mouse. In the development of in vitro culture systems, a detailed characterization of the cultured cells within the framework of the epithelial cell lineages found in vivo is crucial. Monoclonal antibodies are useful tools for defining the profile of antigens expressed by the basal and luminal cells in the normal gland and in distinguishing subclasses between these two major groups. When these same reagents are used to characterize breast cancers, the majority are found to show the phenotype of luminal cells, with a small subset showing some evidence of basal markers. Luminal epithelial cells cultured from milk or reduction mammoplasty tissue have a short life span in vitro but can be immortalized using SV40TAg. Demonstrably malignant cells are difficult to culture from primary breast cancer, but ER+ and ER- cell lines showing the luminal phenotypes have been readily developed from metastases: some ER- breast cancer cell lines show a more undifferentiated phenotype, and these may have developed from tumours expressing basal markers. As with in vitro culture, it is difficult to obtain tumour growth in the nude mouse from primary breast cancer specimens, and established cell lines are also difficult to grow in this animal. We have focused our studies on cell lines with the luminal phenotype developed from milk. These non-tumorigenic cell lines differ from breast cancer cell lines (a) in being able to form organized three dimensional structures in the presence of an extracellular matrix and (b) in the correct glycosylation of the polymorphic epithelial mucin, which is expressed and aberrantly glycosylated in cancers. These cell lines are therefore being used to study the mechanisms underlying morphogenesis and the processing of PEM, and also as recipients for oncogenes and proto-oncogenes. PMID- 8348540 TI - Tissue reconstitution models of breast cancer. AB - Oncogenes have been expressed in mammary epithelium by reconstituting epithelium in vivo from mammary cells. Genetically manipulated primary cultures are transplanted into a mammary fat pad from which the natural epithelium has been removed, where they reform an epithelium in which a few cells express the oncogene. Genes can be expressed in other tissues in a similar way. A wide variety of oncogenes have a clearly observable effect on the pattern of growth of mammary epithelium. Expression of individual oncogenes usually produces stable, characteristic patterns of abnormal growth that can be regarded as preneoplastic states. Different oncogenes produce a very diverse variety of such growth patterns, by altering branching pattern, inducing formation of alveoli, causing epithelium to multilayer and/or altering hormone dependence. Myc and wnt1 seem to enable cells to overgrow neighbouring normal cells, suggesting that they promote clonal expansion, whereas others give focal lesions. Oncogene co-operation can be studied by introducing further oncogenes into preneoplastic epithelium, for example the introduction of ras into epithelium that already expresses activated myc gives tumours. The effects of both neu/c-erbB2 and myc on mouse mammary epithelium may mimic events in human breast, encouraging the hope that this will prove a way to model human breast cancer. The tissue reconstitution approach promises to reconstruct tumour development in more detail than the transgenic systems are able to, showing the development of focal lesions, the restraining effects of normal on transformed cells and the expansion of clones of hyperplastic cells at the expense of their normal neighbours. PMID- 8348541 TI - Influence of sulfate and carboxylate groups on the conformation of chondroitin sulfate related disaccharides. AB - 1H NMR and 13C NMR spectral parameters of eight sulfated uronic acid containing disaccharides 1-8 were used to determine the conformational preferences that depend on the pattern of sulfation. Three sulfated derivatives of benzyl beta-D Gal-(1-->4)-beta-D-GlcA (1), its 6'-sulfate 2, 4'-sulfate 3, and 4',6'-disulfate 4 were used as models for the beta-(1-->4) glycosidic linkage of chondroitin sulfates and three sulfated derivatives of benzyl beta-D-GlcA-(1-->3)-beta-D-Gal (5), its 6-sulfate 6, 4-sulfate 7, and 4,6-disulfate 8 were used as models for the beta-(1-->3) glycosidic linkage of chondroitin sulfates. To determine the dependence of conformational preferences on the charged groups, the sulfated disaccharides 2, 3, and 4 were compared to their unsulfated parent compound 1, and 6, 7, and 8 were compared to their parent compound 5. The 3JH-5,H-6 coupling constants were determined by high-order analysis of the spin systems, and from these the preferred populations of the hydroxymethyl groups were calculated. Selective 1D NOEs and ROEs were measured from H-1' across the glycosidic linkage to obtain the average distance of the protons adjacent to the glycosidic linkage. Derivatives of beta-D-Gal-(1-->4)-beta-D-GlcA carrying a sulfate group in the 6' position (2) and in the 4'- and 6'-position (4) show a slight repulsive effect between the 6'-sulfate groups and the carboxylate group as expressed in small changes of the preferred populations of the glycosidic linkage and the sulfonyloxymethyl group. The 4-sulfate groups in 3 and 4 do not show a significant influence on the glycosidic linkage. However, the two sulfate groups in 4 exhibit a repulsive effect leading to a very high population of the gt conformation of the sulfonyloxymethyl group. In contrast hereto, the sulfate group at C-4 of beta-D-GlcA-(1-->3)-beta-D-Gal disaccharides 7 and 8 and the carboxylate group exert an attractive interaction that leads to a change of the conformation of the glycosidic linkage in 7 and 8 by about 30 degrees. The 6 sulfate groups of the disaccharides 6 and 8 show a slight repulsive interaction with the carboxylate and/or 4-sulfate group. Changes in 13C NMR chemical shifts support the interpretation obtained from the NOE and ROE analysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8348542 TI - Synthesis and NMR spectroscopic investigation of oligosaccharides containing Kdo and L-glycero-D-manno-heptopyranosyl residues. AB - The disaccharides O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->8) sodium (allyl 3-deoxy-beta-D-manno-2-octulopyranosid)onate (8), O-L-glycero-alpha D-manno-heptopyranosyl-(1-->7)-sodium (allyl 3-deoxy-beta-D-manno-2 octulopyranosid)onate (12), and O-alpha-D-mannopyranosyl-(1-->7)-sodium (allyl 3 deoxy-beta-D-manno-2-octulopyranosid)onate (21) and the branched trisaccharides O L-glycero-alpha-D-manno-heptopyranosyl-(1-->7)-[O-(sodium 3-deoxy-alpha- and beta-D-manno-2-octulopyranosylonate)-(2-->8)]-sodium (allyl 3-deoxy-beta-D-manno 2-octulopyranosid)onate (15 and 16) and O-alpha-D-mannopyranosyl-(1-->7)-[O (sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->8)]-sodium (allyl 3 deoxy-beta-D-manno-2-octulopyranosid)onate (24) were prepared. Per-O-acetylated mannopyranosyl or Kdo bromide derivatives were employed for the glycosylation steps under Helferich conditions, whereas the imidate derivative 9 was used for the coupling of the L-glycero-D-manno-heptopyranosyl residues. The oligosaccharides were fully characterized by NMR spectroscopic data. Their structures correspond to an artificial linkage pattern providing a potential cross-reactive epitope for antibodies directed against the inner-core-region of enterobacterial as well as chlamydial lipopolysaccharides. PMID- 8348543 TI - Structures of the amylopectins of waxy, normal, amylose-extender, and wx:ae genotypes and of the phytoglycogen of maize. AB - Average chain lengths and beta-amylolysis limits have been determined for the waxy and ae/wx genotypes of mature maize starch, and for the amylopectin fractions of normal and amylose-extender starches (prepared by precipitation with concanavalin A), rabbit-liver glycogen, phytoglycogen, and waxy rice starch. All amylopectin samples had similar A:B chain ratios of > 1 and the two glycogens had ratios of < 1. This finding led to average frequencies of substitution of B chains over the whole molecule of > 2 for the amylopectins and < 2 for the glycogens. An equation for the number of tiers for a molecule with various frequencies of substitution of B chains and chain lengths has been used to determine the effect of variation in average frequency of branching and average chain length on structure. PMID- 8348544 TI - Isolation and characterisation of hemicelluloses from sunflower hulls. AB - The hemicelluloses extracted from sunflower hulls by repeated alternating oxidative and alkaline treatments were purified by precipitation with Cetavlon and then ion-exchange chromatography on DEAE-trisacryl. The resulting fractions were examined by hydrolysis, methylation, GLC-MS, and NMR spectroscopy. The hemicelluloses are of the glucuronoxylan type with the following structure -->4) beta-D-Xylp-(1-->4)-[4-O-Me-alpha-D-GlcpA-(1-->2)]-bet a-D-Xylp-(1-->. The polysaccharides differed in the amount of branching; the ratio of the main fraction 4-O-MeGlcA:Xyl was 1:8-9. PMID- 8348545 TI - Structural characterization of endo-glycanase-generated oligoglycosyl side chains of rhamnogalacturonan I. AB - Rhamnogalacturonan I (RG-I) has been isolated from the walls of suspension cultured sycamore cells (Acer pseudoplatanus), and additional structural features of the polysaccharide were elucidated. Treatment of RG-I with a purified endo-(1- >5)-alpha-L-arabinanase released a series of arabinose-containing oligosaccharides with degrees of polymerization (dp's) between 2 and 20. These oligosaccharides were shown, by glycosyl-linkage composition analysis, to contain terminal, 5-, and (3-->5)-linked Araf residues. These results provide evidence that a branched arabinan is attached to the backbone of RG-I. RG-I was freed of 95% of its arabinosyl residues by treating the polysaccharide with a combination of endo-(1-->5)-alpha-L-arabinanase and alpha-L-arabinosidase. No galacturonic acid was released by these enzymes, which is evidence that the arabinosyl containing portions of the side chains do not contain galactosyluronic acid residues. The galactose-containing portions of the side chains of RG-I were not fragmented by an endo-(1-->4)-beta-D-galactanase. However, approximately 85% of the galactose and small amounts of galacturonic acid were released by digestion of arabinose-depleted RG-I with a combination of endo- and exo-beta-D galactanases. The galacturonic acid may have been released by small amounts of an exo-alpha-galactosyluronidase contaminating the galactanases. Treatment of RG-I with this mixture of endo- and exo-glycanases resulted in a relatively size homogeneous, almost side chain-free backbone composed of the O-acetylated diglycosyl repeating unit -->4)-alpha-D-GalpA-(1-->2)-alpha-L-Rhap. A combination of 1H NMR spectroscopy and periodate oxidation established that the backbone repeating unit contained a single O-acetyl substituent on C-2 or C-3 of each galactosyluronic acid residue. PMID- 8348546 TI - The purification of commercially available endo-alpha-L-arabinanases and alpha-L arabinosidase for use in the structural analysis of pectic polysaccharides. PMID- 8348547 TI - NMR spectroscopy of nystose. PMID- 8348548 TI - A convenient synthesis of N-acetyllactosamine-linked oligosaccharides from phenyl 3,6,2',3',4',6'-hexa-O-acetyl-2-deoxy-2-phthalimido-1-thio-beta-lactopy ranoside . PMID- 8348549 TI - A practical synthesis of 2-azidoethyl alpha-glycosides: useful spacer-arm glycosides for the synthesis of neoglycoconjugates. PMID- 8348550 TI - FABMS/derivatisation strategies for the analysis of heparin-derived oligosaccharides. AB - Derivatisation/FABMS strategies applicable to the structure analysis of low microgram quantities of heparin-derived oligosaccharides are described. Negative and positive FAB data from permethyl derivatives and positive FAB data from the products of subsequent methanolysis are reported for sulfated tetrasaccharides prepared by nitrous acid degradation of heparin. The preparation and FAB behaviour of acetylated derivatives of sulfated oligosaccharides are described for the first time, and the stability of the sulfate groups to base-catalysed acetylation is demonstrated. The acetylation/FABMS methodology, which yields high quality data, shows promise for the characterisation of a wide range of sulfated glycoconjugates. PMID- 8348551 TI - Electrosyntheses of disaccharides from phenyl or ethyl 1-thioglycosides. AB - Constant current electrolyses of the glycosyl donors phenyl and ethyl 2,3,4,6 tetra-O-benzyl-1-thio-beta-D-glucopyranoside in dry acetonitrile in the presence of various primary and secondary sugar alcohols, performed in an undivided cell, gave beta-linked disaccharide derivatives selectively in good yields. Phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-beta-D-glucopyranoside gave the beta-glucosides exclusively in good to moderate yields. PMID- 8348552 TI - Synthesis of a tetrasaccharide donor corresponding to the O-specific polysaccharide of Shigella dysenteriae type 1. AB - O-(2,4-Di-O-benzoyl-3-O-chloroacetyl-alpha-L-rhamnopyranosyl)-(1--> 2)-O-(3,4,6 tri-O-benzoyl-alpha-D-galactopyranosyl)-(1--> 3)-O-(2-acetamido-4,6-di-O-acetyl-2 deoxy-alpha-D-glucopyranosyl)-(1--> 3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (1) was synthesized in a stepwise manner, using the following monosaccharide units: 2-(trimethylsilyl)ethyl 2,4-di-O-benzoyl-alpha-L rhamnopyranoside, 2-azido-4,6-O-benzylidene-3-O-chloroacetyl-2-deoxy-beta-D glucopyranosyl chloride, methyl 3,4,6-tri-O-benzoyl-2-O -(4-methoxybenzyl)-1-thio beta-D-galactopyranoside, and 2,4-di-O-benzoyl-3-O-chloroacetyl-alpha-L rhamnopyranosyl chloride. Compound 1 corresponds to a complete tetrasaccharide repeating unit of the O-specific polysaccharide of the lipopolysaccharide of Shigella dysenteriae type 1. PMID- 8348553 TI - Synthesis and antileukemic activity of certain D-fucopyranosyl nucleosides. AB - Based upon previously discovered antileukemic properties of 9-beta-D fucopyranosyladenine (1) in cell culture, four new nucleosides containing naturally occurring bases have been prepared from D-fucose. alpha-D-Fucopyranose tetraacetate was condensed with the silylated bases in either acetonitrile or 1,2 dichloroethane with tin(IV) chloride as the catalyst. The intermediate blocked nucleosides were obtained in crystalline form and deacetylated with methanolic sodium methoxide. 1-beta-D-Fucopyranosyluracil (8), 1-beta-D-fucopyranosylthymine (9), 1-beta-D-fucopyranosylcytosine (10) as the hydrochloride salt, and 7-beta-D fucopyranosylguanine (11) were crystallized, and their structures were verified by spectroscopic techniques. Nucleosides 8 and 9 had only borderline activity against leukemia L1210 cells grown in culture, whereas nucleoside 11 had activity equal to 1. However, nucleoside 10 proved to be twice as active as either 1 or 11. The antileukemic activity, which was due to the inhibition of cell division, was reversible by transfer of the arrested cells to fresh media or by the addition of cytidine. PMID- 8348555 TI - A convenient synthesis of beta-D-galactosyl disaccharide derivatives using the beta-D-galactosidase from Bacillus circulans. AB - beta-D-Gal-(1-->4)-beta-D-GlcNAc-OC6H4NO2-p (p-nitrophenyl N-acetyl-beta lactosaminide) and beta-D-Gal-(1-->6)-beta-D-GlcNAc-OC6H4NO2-p (p-nitrophenyl N acetyl-beta-isolactosaminide) were regioselectively synthesized from lactose and p-nitrophenyl 2-acetamido-2-deoxy-glucopyranoside, employing transglycosylation by the beta-D-galactosidase from Bacillus circulans and by controlling the concentration of organic solvent in the reaction system. The (1-->4)-linked disaccharide was formed exclusively when the concentration of organic solvent was high, whereas the (1-->6)-linked isomer was produced with a low concentration. Further utilization of the transglycosylation by the enzyme led to the regioselective formation of beta-D-Gal-(1-->4)-D-GalNAc and beta-D-Gal-(1-->4) beta-D-GalNAc-OC6H4NO2-p. With the enzyme, beta-D-galactosyl transfer occurred preferentially at the O-4 position of GlcNAc and GalNAc, regardless of the configuration of the hydroxyl group. PMID- 8348554 TI - Total synthesis of the carbohydrate-protein linkage region common to several mammalian proteoglycans. AB - A stereocontrolled synthesis of beta-D-GlcpA-(1--> 3)-beta-D-Galp-(1-->3)-beta-D Galp-(1-->4)-beta-D-Xylp-(1 --> O)-L-Ser-Gly, the common glycopeptide sequence of the carbohydrate-protein linkage region of most mammalian proteoglycans, was achieved by use of O-[2-(trimethylsilyl)ethyl 2,3,4-tri-O-benzoyl-beta-D glucopyranosyluronate] -(1-->3)-O-(2,4,6-tri-O-benzoyl-beta-D-galactopyranosyl) (1-->3)-O-(2,4, 6-tri -O-benzoyl-beta-D-galactopyranosyl)-(1-->4)-2,3-di-O benzoyl-alpha, beta-D- xylopyranosyl trichloroacetimidate as the key intermediate. Condensation of this glycosyl donor with suitably protected L-seryl glycine dipeptide segments, and peptide chain elongation, allowed the construction in high yield of complex structures of this linkage region. PMID- 8348556 TI - Structural investigation of the capsular polysaccharide produced by a novel Klebsiella serotype (SK1). Location of O-acetyl substituents using NMR and MS techniques. AB - The capsular polysaccharide of Klebsiella SK1 was investigated by methylation analysis, Smith degradation, and 1H NMR spectroscopy. The oligosaccharides (P1 and P2) obtained by bacteriophage phi SK1 degradation of the polymer were studied by methylation analysis, and 1D- and 2D-NMR spectroscopy. The resulting data showed that the parent repeating unit is a branched pentasaccharide having a structure identical to the revised structure recently proposed for Klebsiella serotype K8 capsular polysaccharide. [Formula: see text] The 2D-NMR data showed that one third of the glucuronic acid residues in the SK1 polymer are acetylated at O-2, O-3, or O-4. FABMS studies confirmed the presence of monoacetylated glucuronic acid residues. Thus, the relationship between the Klebsiella K8 and SK1 polymers is akin to that found for Klebsiella polysaccharides K30 and K33, which have been typed as serologically distinct yet their structures differ only in the degree of acetylation. PMID- 8348557 TI - Pyrolysis of inulin, glucose, and fructose. AB - The pyrolytic behavior of inulin, a (2-->1)-linked fructofuranan, is described. Parallel investigations of the pyrolysis of glucose and of fructose were conducted to supplement the inulin results and to aid comparison with previous results from glucans. Effects of neutral and basic additives are emphasized. As with glucans, the addition of such additives (especially basic) increases the yields of the one-, two-, and three-carbon products (as well as of hexosaccharinolactones), while generally decreasing the yields of anhydro sugar and furan derivatives. The former products include glycolaldehyde, acetol, dihydroxy-acetone, acetic acid, formic acid, and lactic acid. Mechanistic speculations are made regarding the origins of these compounds, as well as of furan derivatives and saccharinic acid lactones. Parallels with alkaline degradation are considered. PMID- 8348558 TI - Comparison of the activity of two chondroitin AC lyases on dermatan sulfate. PMID- 8348559 TI - Cytokine combinations in immunotherapy for solid tumors: a review. AB - The use of cytokines alone or in combination with other cytokines or cytotoxic drugs has had a profound effect upon widely metastatic disease in many cases. However, despite the encouraging results in early trials, there is much room for improvement. Few responses to these combinations are complete, and toxicity has in some cases been quite severe. Changes in dose, route, or schedule of administration of the drugs, or the development of cytokine analogs may lead to more efficacious and less toxic regimens. In addition, new cytokines such as interleukin(IL)-7 and IL-12 are currently under investigation for potential use in future immunotherapy trials. These prospects and the use of cytokine combinations are promising advances in the treatment of human cancer. PMID- 8348560 TI - Cytotoxic cell function and phenotypic analysis of peripheral blood mononuclear cells in cancer patients treated with low-dose interleukin-2 and mitomycin C. AB - We previously found that the ability of peripheral blood mononuclear cells (PBM) of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C administration. On the basis of the clinical findings, we designed a treatment regimen comprised of 12 mg/m2 mitomycin C i.v. on day 1 and 700 U/m2 recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Of 25 patients with advanced carcinoma, 9 had a partial response and 3 had a minor response. Cytotoxic cell function, including natural killer activity, lymphokine-activated killer (LAK) activity, and the ability to generate LAK cells, and lymphocyte subsets in PBM was measured 1 day before and after either the first or second course of this therapy. The relationship between these parameters and the clinical antitumor response to this treatment was examined. Although the cytotoxic activities were significantly augmented after either the first or second treatment course, no positive correlation was observed between the changes in these cytotoxic activities and the clinical response to this therapy, when patients who either showed a partial response or whose disease remission was partial or minor were defined as responders. Further, phenotypic analysis showed a significant increase in CD2+, CD3+, CD4+ and CD4+Leu8- cells after the first course, and CD25+ cells after either the first or second course of this treatment. The percentages of CD2+ and CD25+ cells were significantly elevated only in responders but not in nonresponders, suggesting the increase in these subsets was related to clinical response. PMID- 8348561 TI - Interleukin-5 induces tumor suppression by peritoneal exudate cells in mice. AB - The antitumor activity of peritoneal exudate cells (PEC) induced by murine interleukin-5 (mIL-5) was examined using Meth-A sarcoma cells transplanted into the peritoneal cavity of mice. Although in vitro treatment of Meth-A sarcoma cells with mIL-5 did not result in inhibition of their growth, treatment of mice intraperitoneally with mIL-5 (1 microgram/day) from day -5 to +5 (tumor cells were inoculated on day 0) led to a significant increase in survival or even rejection of tumor cells. This antitumor effect depended on the dose of mIL-5. Interestingly, there was identical therapeutic activity when the protocol of days -10 to -1 was used as opposed to -5 to +5. In addition, post-treatment with mIL-5 from day +1 to +10 was ineffective. This suggests that the therapeutic activity of IL-5 is largely prophylactic. Under the former condition, the number of PEC was found to increase over 50-fold when compared to levels in control mice. Moreover, the antitumor effect of mIL-5 was completely abolished by subcutaneous injection of anti-mIL-5 monoclonal antibodies. The treatment of mice injected intraperitoneally with human IL-2 also resulted in an increase in survival. Winn assay experiments using PEC recovered from mIL-5-treated mice (1 microgram/day, from day -10 to -1) revealed that these PEC could mediate antitumor activity against Meth-A sarcoma cells. Furthermore, when the cured mice were re-injected with Meth-A sarcoma cells or syngeneic MOPC104E cells, they could reject Meth-A sarcoma cells but not MOPC104E cells, indicating that immune memory had been generated. These results suggest that IL-5 augmented the PEC tumoricidal activity but we have no indication that the tumoricidal activity was mediated through a mIL-5-dependent mechanism. PMID- 8348562 TI - Effect of allogeneic tumor cells, interleukin-2 and interleukin-6, on the growth of subcutaneous syngeneic tumors. AB - In the present study we demonstrate the ability of allogeneic M3 tumor cells to induce an antitumor response against the syngeneic tumor, when injected locally together with syngeneic B16 melanoma cells. The replacement of the allogeneic tumor cells with either syngeneic or allogeneic splenocytes had no effect on the growth of the syngeneic tumor. Systemic administration of both interleukin-2 (IL 2) and IL-6 did not affect the antitumor response induced by allogeneic tumor cells. When mice, previously injected with B16 and M3 cells, were rechallenged subcutaneously with B16 tumor cells at a different anatomical site, an inhibitory effect in some, but not all, experiments was observed. Systemic injections of either IL-2 or IL-6 did not alter the antitumor effects of the allogeneic and syngeneic tumor-cell mixtures. The significance of our results in developing immunotherapy modalities based on active immunization with allogeneic tumor cells and selected cytokines is discussed. PMID- 8348563 TI - In vitro expansion and analysis of T lymphocyte microcultures obtained from the vaccination sites of cancer patients undergoing active specific immunization with autologous Newcastle-disease-virus-modified tumour cells. AB - In order to understand further the effects of Newcastle-disease-virus(NDV) modified tumour vaccines we investigated the feasibility of isolating lymphocytes from the site of injection of patients undergoing postoperative active specific immunization (ASI) with autologous NDV-modified tumour cells. Delayed-type hypersensitivity(DTH)-like reactions from five cancer patients were surgically removed, minced and the tissue particles were digested with collagenase and DNase. Lymphoid cells recovered were expanded in a highly efficient limiting dilution analysis system optimized for T cell growth [Moretta et al. (1983) J Exp Med 157: 743] and lymphocyte microcultures (clonal probability > 0.8) could be grown for up to 1 year. Analysis of the microcultures for phenotype and function showed that the majority were positive for CD4 (92%) and TCR alpha beta (96%). Concanavalin-A-induced production of interleukin-2 (IL-2), IL-6, interferon gamma and tumour necrosis factor alpha was detected in more than 70% of the microcultures. Lectin-dependent cytotoxicity was only very rarely observed. The general characteristics of the microcultures obtained support the notion of a DTH like reaction taking place at the site of tumour cell challenge. The possibility of in vitro expansion and cultivation of T lymphocytes from ASI vaccination sites should help to elucidate further the role of these cells in active specific immunization against autologous tumour cells. PMID- 8348564 TI - Synergetic effect of interleukin-2 and cellular cytotoxicity against a novel tumor-associated carbohydrate antigen Le(a)/Le(a) (dimeric Le(a)) mediated by monoclonal antibody NCC-ST-421 in adoptive immunization using SCID mice. AB - The murine IgG3 monoclonal antibody NCC-ST-421, raised against a human gastric cancer, shows strong reactivity with dimeric Le(a) (Le(a)/Le(a); V4FucIII4FucLc6Cer) expressed on gastrointestinal cancer cells. ST-421 reacted minimally with non-dimeric or simple Le(a) expressed on normal tissues. ST-421 is capable of mediating both antibody-dependent cellular cytotoxicity (ADCC) with human peripheral blood lymphocytes, and complement-dependent cytotoxicity with human complement. Interleukin-2 (IL-2) modulates the function of immunocytes, in particular inducing lymphokine-activated killer (LAK) cell activity and enhancing ADCC. We therefore employed combination immunotherapy with IL-2, LAK, and ST-421 induced ADCC in vitro and in mice with severe combined immunodeficiency (SCID), using target tumor cells expressing Le(a)/Le(a) antigen. ADCC against human colon cancer cell lines in vitro was enhanced three to four times after preincubation with IL-2. Addition of IL-2 reduced the amount of ST-421 required for efficient ADCC 10- to 100-fold. ADCC was activated by IL-2 earlier (1 day) than the generation of LAK cells (3-4 days), and at lower concentration of IL-2. These effects were specific for ST-421, as demonstrated by experiments with irrelevant antibody or irrelevant target cells. An anti-(Fc receptor) antibody blocked the ADCC but not the LAK activity in vitro. The enhancement of ADCC by IL-2 may be caused by activation of effector cells expressing Fc receptors. In vivo experiments using SCID mice inoculated with human colon cancer showed a significant tumor-growth-suppressive effect after combined therapy using human peripheral blood lymphocytes, LAK, IL-2, and ST-421. In summary, adoptive immunization with human lymphocytes activated by IL-2 and ST-421 effectively suppressed growth of gastrointestinal cancer cells expressing Le(a)/Le(a). PMID- 8348565 TI - Induction of an immune network cascade in cancer patients treated with monoclonal antibodies (ab1). I. May induction of ab1-reactive T cells and anti-anti idiotypic antibodies (ab3) lead to tumor regression after mAb therapy? AB - The antitumor effector functions of unconjugated monoclonal antibodies in cancer therapy are complex. Direct cytotoxic mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytolysis and apoptosis have been suggested. Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies as well as T cell (T2 and T3 respectively) responses have also been proposed to be of clinical importance. In this study induction of an immune network cascade in patients with colorectal carcinoma, treated with mAb 17-1A (ab1) was assessed. All patients developed anti-idiotypic antibodies (ab2) of the IgG class after treatment with ab1 and four of nine patients showed induction of mouse Ig reactive T cells [a proliferative response to F(ab')2 fragments of ab1]. Patients with such a T cell response developed anti-anti-idiotypic antibodies (ab3), while those lacking the T cell reactivity failed to mount an ab3 response. Three of four patients with a T cell response achieved a tumor response to mAb therapy. Thus, all responding patients belonged to the group of individuals developing ab3. Induction of mAb(ab1)-reactive T cells as well as an immune network cascade might be important antitumor effector functions of mAb and should be considered in the future design of mAb-based therapy protocols in cancer patients. PMID- 8348567 TI - Endogenous myocardial protective (antiarrhythmic) substances. PMID- 8348566 TI - Critical factors for liposome-incorporated tumour-associated antigens to induce protective tumour immunity to SL2 lymphoma cells in mice. AB - Physical and immunogenic properties of reconstituted membranes designed for the presentation of tumour-associated antigens (TAA) to the immune system are described. Proteins and lipids of crude membranes of SL2 murine lymphosarcoma cells were partially solubilized with octylglucoside. Reconstituted membranes, consisting mainly of unilamellar vesicles with a diameter of 0.03-0.15 microns, were formed by detergent removal and were purified by floatation in a discontinuous sucrose gradient to remove non-lipid-bound protein. Subcutaneous immunization of syngeneic mice with reconstituted membranes or with purified reconstituted membranes induced protection against an intraperitoneal challenge with 10(3) viable SL2 cells. Reconstituted membranes were more immunogenic than crude membranes in immunoprotection experiments when compared on the basis of protein dose. Detergent removal was required to obtain an immunogenic presentation form of SL2 membrane antigens and to avoid toxicity associated with the detergent. Reconstitution of SL2 membranes in the presence of exogenous phospholipid slightly increased the fraction of protein that associated with the reconstituted membranes. However, the immunogenicity of the solubilized membrane TAA was not significantly affected by the presence of exogenous phospholipid. The reconstitution procedure described may be useful in identifying membrane factors required for the induction of immune responses against TAA. The versatility of the system may be employed to develop safe alternatives for whole-cell vaccines. PMID- 8348568 TI - Endogenous chemical mediators of ventricular arrhythmias in ischaemic heart disease. AB - The causes of ventricular arrhythmias in the acute setting of coronary artery disease (myocardial ischaemia and reperfusion) may be approached using two paradigms. One, the electrophysiological paradigm (disturbance of ionic homeostasis, electrogenesis, and conduction) has not been addressed in detail here. Instead, we have focused on the concept of a chemical paradigm of arrhythmogenesis. Many endogenous chemical substances (derived from the myocardium, nerves, blood plasma, platelets, leucocytes, and endothelium) accumulate in the ischaemic tissue or are produced during reperfusion and many of these have been suggested to modulate ventricular arrhythmias. Some substances may be arrhythmogenic and others may be antiarrhythmic. Together they determine whether or not arrhythmias occur. Potentially arrhythmogenic substances include potassium, catecholamines, cAMP, histamine, 5-HT, lysophosphatidylcholine, palmitylcarnitine, platelet activating factor, prostaglandins, leukotrienes, thromboxane A2, angiotensin II, endothelin, opioids, protons, calcium, and free radicals. We have considered each of these, with the objective of evaluating which are important in arrhythmogenesis in acute ischaemia and reperfusion. Two alternative models of arrhythmogenesis are possible in the context of the chemical paradigm: a series model (where one substance or its effects determines the arrhythmogenicity of another) and a parallel model (where numerous substances operate independently to cause ventricular arrhythmias). It is not yet clear which model is most appropriate; a combination of the two is possible, so a working prototype has been constructed which accommodates both. A set of criteria (hitherto lacking) for establishing whether a substance is sufficient and necessary for arrhythmogenesis is proposed. Some generalisations are given on approaches to establishment of these criteria for putative arrhythmogenic substances. Finally, we have considered how arrhythmogenic drug development may be influenced by using the chemical paradigm as an alternative to the electrophysiological paradigm of arrhythmogenesis. PMID- 8348569 TI - Severe neutrophil depletion by leucocyte filters or cytotoxic drug does not improve recovery of contractile function in stunned porcine myocardium. AB - OBJECTIVE: The contribution of neutrophils to myocardial injury during stunning remains controversial because of conflicting results in neutropenic animals. The goal of this study was to compare the recovery of function in stunned myocardium using two distinct methods for inducing neutropenia in pigs. METHODS: Three groups of pigs were studied: control (n = 6), and made neutropenic by either Leukopak blood filters (n = 7), or cyclophosphamide (n = 7, 50 mg.kg-1 intravenously 4 d prior to study). In anaesthetised open chest pigs, with the heart paced at 110 beats.min-1, the left anterior descending coronary artery was perfused with an extracorporeal circuit at controlled coronary pressure (CP) and the regional coronary blood flow was measured. Systolic wall thickening was determined by sonomicrometry in the left anterior descending and circumflex coronary artery regions. The protocol consisted of 15 min of low flow ischaemia (CP = 40 mm Hg), followed by a staged reperfusion over 10 min back to baseline (CP = 90 mm Hg), and continued for 2 h. Blood filtration was initiated prior to ischaemia and stopped after 90 min reperfusion. RESULTS: In both treated groups during ischaemia and the initial 60 min of reperfusion the neutrophil count was severely depleted to < 5% compared to the control group. Aortic pressure, coronary blood flow during ischaemia, area at risk, and systolic wall thickening in the circumflex region were similar between groups. Recovery of systolic wall thickening in the left anterior descending region after reperfusion was equivalent in all three groups. In the filter group, arrhythmias during ischaemia and reperfusion were significantly less. CONCLUSION: As assessed in the pig model of myocardial stunning and using two different methods, severe neutropenia does not reduce the depression of contractile function. PMID- 8348570 TI - Role of neutrophils in myocardial stunning after brief ischaemia: the end of a six year old controversy (1987-1993) PMID- 8348571 TI - Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat. AB - OBJECTIVE: Activation of the intrarenal renin-angiotensin system may contribute to the pathophysiology of heart failure by accelerating the generation of angiotensin II at local sites within the kidneys. Activation of the local intrarenal renin-angiotensin system occurs in rats and with mild heart failure. The aim of the present study was to examine components of the circulating as well as the intrarenal renin-angiotensin system in rats with severe heart failure. METHODS: Six weeks after experimental myocardial infarction (heart failure, HF; n = 8) or sham operation (control, C; n = 6), haemodynamics and the circulating and intrarenal components of the renin-angiotensin system were studied. RESULTS: HF rats were characterised by large infarctions (scar tissue > 40% of the left ventricular circumference). In comparison to sham operated controls, large myocardial infarctions resulted in severe heart failure with decreased systolic [108(SEM 3) mm Hg v 132(3) in C; p < 0.001] and diastolic arterial blood pressure [83(3) mm Hg v 95(2) in C; p < 0.05], decreased left ventricular systolic pressure [109(3) mm Hg v 132(3) in C; p < 0.005] and increased left ventricular end diastolic pressure [27(2) mm Hg v 5(1) in C; p < 0.0001]. In rats with severe heart failure, the circulating renin-angiotensin system was activated, with an increase in plasma renin activity (3.5-fold, p < 0.05) and plasma angiotensin II concentration (threefold, p < 0.01). In parallel, the intrarenal renin angiotensin system was activated in severe heart failure. Increases occurred in renal renin mRNA level (1.7-fold, p < 0.01), renal angiotensinogen mRNA level (1.8-fold, p < 0.05), and renal angiotensin II concentration (twofold, p < 0.05) compared to C. Intrarenal angiotensin II concentrations exceeded plasma levels by a factor of 50 and were positively correlated with renal angiotensinogen mRNA levels (r = 0.874, p < 0.001), suggesting that local synthesis is the major source of angiotensin II found in the kidney. CONCLUSIONS: The intrarenal renin angiotensin system may be selectively activated in mild heart failure, while both circulating and intrarenal renin-angiotensin systems are induced as the extent of left ventricular function worsens. PMID- 8348572 TI - Reduction of experimental myocardial infarct size by infusion of lactosylphenyl Trolox. AB - OBJECTIVE: The aim was to determine if lactosylphenyl Trolox could improve myocardial resistance to ischaemia and reperfusion. Lactosylphenyl Trolox is derived by coupling p-aminophenyl-beta-D-lactopyranoside to Trolox. Trolox, a polar analogue of vitamin E, has been found to protect human cardiomyocytes against oxyradicals and to reduce myocardial damage by 66% in a canine ischaemia reperfusion model. METHODS: New Zealand white rabbits (weighing approximately 3.5 kg) were subjected to 1 h ischaemia by ligation of the main branch of the anterior ventricular coronary artery. Approximately 1-2 min before release of ischaemia, a 30 ml bolus of saline (placebo control) or saline containing lactosylphenyl Trolox was injected into the right external jugular vein, followed by 3 h reperfusion. The area at risk was identified by staining with Evans Blue. Area of necrosis was indicated by tetrazolium red staining, confirmed by histopathology and quantified by planimetry. RESULTS: The control group (n = 6) had 46.6(SD 10.0)% necrosis of the area at risk but the lactosylphenyl Trolox treated groups (n = 6 per group) had reduced necrosis: 34.0(6.5)%, 17.4(8.2)%, and 6.9(3.6)% at doses of 2.5, 5.0, and 10 mumol.kg-1, respectively (each with p < 0.05 v control value). These translated to 48.6(14.0)%, 62.7(17.6)%, and 85.3(7.8)% myocardial salvage, respectively. In contrast, the salvages achieved with 2.5 and 10 mumol.kg-1 of Trolox were 31.0(11.0)% and 62.1(18.9)% respectively (both p < 0.05 v lactosylphenyl Trolox). CONCLUSIONS: Lactosylphenyl Trolox reduces myocardial infarct size more effectively than Trolox in a rabbit model of ischaemia-reperfusion. PMID- 8348573 TI - Dobutamine restores the reduced efficiency of energy transfer from total mechanical work to external mechanical work in stunned porcine myocardium. AB - OBJECTIVE: In order to determine whether the relatively high oxygen consumption of stunned myocardium is related to decreased mechanical efficiency, myocardial oxygen consumption (MVO2) and its major determinants were studied in 10 open chest anaesthetised pigs. METHODS: According to the time varying elastance concept, MVO2 is determined by contractility (Emax) and total mechanical work (PLA), which is the sum of the external work (EW) and potential energy (PE). Mechanical efficiency (EW/MVO2) equals the product of EW/PLA (= efficiency of energy transfer or EET) and PLA/MVO2. Emax is the slope of the end systolic pressure-segment length relationship, determined by gradually clamping the aorta. PLA is the area enclosed by the end systolic pressure-segment length relationship and the pressure-segment length trajectory. EW is the area of the pressure segment length loop. Systemic haemodynamics, regional segment shortening, and MVO2 were determined at baseline, during stunning (two sequences of 10 min occlusion and 30 min of reperfusion), after a subsequent 50 beats.min-1 increase in heart rate by atrial pacing and additional infusion of 2 micrograms.kg-1.min-1 dobutamine. RESULTS: Stunning decreased segment shortening from 18.2(SEM 1.9)% to 10.2(1.5)%, MVO2 from 4.16(0.27) x 10(-2) to 2.84(0.25) x 10(-2) mumol.beat-1.g 1, and Emax from 47(9) to 23(3) mm Hg.mm-1 (all p < 0.05). PLA decreased by 13(4)%, as EW decreased by 42(6)%, and PE tended to increase. Although EET decreased from 0.58(0.04) to 0.40(0.03) (p < 0.05), there was no decrease in the mechanical efficiency, as an increase in PE caused an increase in PLA/MVO2 which compensated for the decrease in EET. Dobutamine infusion increased Emax and EW per beat to 120(23)% and 67(8)% of baseline, respectively, while MVO2 [4.12(0.53) mumol.beat-1.g-1] and EET [0.57(0.04)] returned to baseline. CONCLUSIONS: In stunned myocardium, mechanical efficiency is not decreased despite a decrease in EET. The increase in EET after dobutamine may explain the lack of the excessive increase in MVO2. PMID- 8348574 TI - Arteriovenous-shunt-mediated increase in venous return causes apparent right coronary arterial autoregulation. AB - OBJECTIVE: Reports of autoregulation in the right coronary vasculature have varied from non-existent to almost perfect. At least some of this discrepancy may be due to failure to account for changes in myocardial metabolism secondary to the method used to vary perfusion pressure. The aim of this study was to determine if the potent autoregulation reported when right coronary perfusion pressure was lowered by opening a large arteriovenous shunt was due to increased right ventricular myocardial oxygen consumption (MVO2) induced by augmented preload and afterload. METHODS: Two protocols were used to produce right coronary perfusion pressures of 100, 80, and 60 mm Hg in anaesthetised dogs. In both protocols the right coronary artery was cannulated and supplied with blood from a pressurised chamber. In protocol 1, right coronary perfusion pressure was decreased independently of aortic pressure, and in protocol 2, aortic pressure was decreased in parallel with right coronary perfusion pressure by opening a large arteriovenous shunt. Right coronary blood flow, central venous pressure, and pulmonary arterial pressure were measured, and right ventricular oxygen extraction and MVO2. Central venous pressure (right ventricular preload) and pulmonary arterial pressure (right ventricular afterload) did not change. In protocol 2, opening the arteriovenous shunt increased venous return, as shown by increased central venous pressure and pulmonary arterial pressure. This increased right ventricular MVO2 at the lower right coronary perfusion pressures and maintained right coronary blood flow at the level recorded when right coronary perfusion pressure was 100 mm Hg. CONCLUSIONS: This apparently potent autoregulation resulted from the shunt induced increase in oxygen consumption at low right coronary perfusion pressures, in contrast to the decreased right ventricular oxygen consumption and right coronary blood flow observed when right coronary perfusion pressure is selectively decreased. PMID- 8348575 TI - Interaction of sympathetic and parasympathetic nervous system on ventricular refractoriness assessed by local fibrillation intervals in the canine heart. AB - OBJECTIVE: The aim was to assess the effects of autonomic nerve stimulation on local ventricular refractoriness by measuring local ventricular fibrillation intervals. METHODS: In 10 dogs on cardiopulmonary bypass, ventricular fibrillation intervals were recorded simultaneously at up to 32 sites before and after neural stimulation. In four dogs (group 1) the response to bilateral stellate ganglion stimulation was measured before and after bilateral cervical vagotomy. In three dogs (group 2) bilateral stellate ganglion stimulation, vagal nerve stimulation, and combined vagal and stellate ganglia stimulation were performed. In three dogs (group 3) the same protocol was applied after total decentralisation of the autonomic nervous system. RESULTS: Bilateral stellate ganglion stimulation shortened the ventricular fibrillation interval at 44-50% of myocardial sites before and after vagotomy, whereas prolongation of the interval was observed at 14-18% of the sites. At higher stimulus strength shortening of the interval was measured at 85% of the sites in the intact and decentralised groups. No prolongation was observed. The shortening was largest in the decentralised group (11.1 ms). Dispersion in refractoriness increased in hearts from all groups, but not in each individual heart. Left, right, or bilateral vagal stimulation was without effect at about 75% of the tested sites. The fact that the response to autonomic nerve stimulation varies from site to site warrants our approach of simultaneous recordings at multiple sites. Dispersion in refractoriness was not affected by vagal stimulation. Combined autonomic stimulation had approximately the same effect on dispersion in refractoriness as bilateral stellate ganglion stimulation alone. However, vagal stimulation attenuated the responses to bilateral stellate ganglion stimulation by some 20% in the decentralised group. CONCLUSIONS: Vagal stimulation has minor effects on ventricular refractoriness, but this is not due to sparse innervation, since vagal stimulation is able to mitigate the effects of sympathetic stimulation in decentralised hearts. PMID- 8348576 TI - Differential cardiac responses induced by nicotine sensitive canine atrial and ventricular neurones. AB - OBJECTIVE: The aim was to study the locations and functions of atrial and ventricular nicotine sensitive neurones. METHODS: In anaesthetised open chest dogs, cardiovascular effects elicited by nicotine (100 micrograms in 0.1 ml 0.9% saline), administered at specific loci of in situ atrial and ventricular ganglionated plexi, were studied before and after decentralisation. RESULTS: Cardiovascular responses were elicited when 41% of atrial and 36% of ventricular ganglionated plexus loci were studied. Subsequently, ganglia were identified adjacent to active sites. When cardiovascular responses were elicited, either tachycardia or bradycardia was induced, depending on the locus investigated. When tachycardia occurred, atrial and/or ventricular forces were augmented. When bradycardia occurred, atrial forces were suppressed. Ventricular fibrillation was induced in two animals when ventricular ganglionated plexus loci were investigated. Cardiovascular responses were not elicited when up to 2000 micrograms of nicotine were administered adjacent to intrinsic cardiac axons, indicating that responses were not primarily due to axonal effects. Control injections of saline (0.1 ml) into active loci did not elicit cardiovascular responses. Following acute decentralisation, responses initiated by nicotine were attenuated or eliminated. Depressor responses were no longer elicited following atropine administration, nor augmentor ones following propranolol administration. CONCLUSIONS: (1) The canine heart contains nicotine sensitive neurones which can induce either augmentor or depressor cardiac effects. (2) Nicotine sensitive atrial neurones modify primarily, but not exclusively, atrial tissues, whereas ventricular ones modify primarily, but not exclusively, ventricular tissues. (3) Nicotine sensitive intrinsic cardiac neurones can interact with central neurones to modulate the heart. PMID- 8348577 TI - Contribution of each wall to biventricular function. AB - OBJECTIVE: Common muscle fibres encircle both ventricles and the ventricles share a common septal wall. This close anatomical association suggests that regional ischaemia and structural integrity may alter systolic function in both the right and the left ventricle. To examine this possibility, we investigated the contribution of each wall to biventricular function. METHODS: Isolated hearts, obtained from anaesthetised rabbits, were perfused with physiological salt solution under constant pressure. Balloons were placed in the right and left ventricles to measure isovolumetric pressure, and pressure-volume curves were obtained. In separate sets of experiments, the left ventricular free wall, right ventricular free wall, or septum was made ischaemic, incised, or injected with glutaraldehyde, respectively. Pressure-volume curves were obtained again. RESULTS: After left ventricular free wall ischaemia (n = 11), right ventricular developed pressure decreased significantly from 27.9(SD 8.9) to 14.1(6.6) mm Hg (p < 0.05), and remained depressed when the left ventricular free wall was further damaged by glutaraldehyde. Cutting the left ventricular free wall (n = 6) decreased right ventricular developed pressure from 28.9(8.6) to 17.8(4.8) mm Hg (p < 0.05), while reapproximating the left ventricular free wall by suturing re established right ventricular developed pressure. After right ventricular free wall ischaemia (n = 7), right ventricular developed pressure decreased from 26.8(6.6) to 24.1(5.7) mm Hg (NS) and left ventricular developed pressure was unaltered. Cutting the right ventricular free wall (n = 7) had no effect on left ventricular developed pressure. Cutting the septum (n = 7) had no obvious influence on right ventricular developed pressure, but dramatically decreased left ventricular developed pressure from 79.2(55.2) to 43.7(32.2) mm Hg (p < 0.05). Injecting glutaraldehyde into the septum (n = 7) decreased both right and left ventricular developed pressures from 22.1(8.5) to 14.0(8.8) and from 78.2(50.5) to 47.9(37.9), respectively. CONCLUSIONS: The results show that the heart should be viewed as a mechanical syncytium. The left ventricular free wall plays a critical role in right ventricular systolic function and may help to explain the right ventricular response to left ventricular ischaemia. On the other hand, in the isolated heart preparation, right ventricular free wall ischaemia has only a minimal effect on left ventricular systolic developed pressure. Altering ventricular septal function affects both right and left ventricular systolic function. PMID- 8348578 TI - Mechanical characteristics of the globally ischaemic heart. AB - OBJECTIVE: The aim was to study the effects of global ischaemia on the mechanical properties of the myocardium. METHODS: Myocardial ischaemia was achieved by incubating the hearts of 160 rats in normal saline at 37 degrees C for periods of up to 24 h. To obtain different degrees of contracture, excess pressure (up to 150 mm Hg) was created in the left ventricles of subgroups of hearts. After incubation the hearts underwent mechanical loading. RESULTS: Ischaemic contracture of cardiomyocytes led to increased rigidity and strength of the myocardium. A pressure of 50 mm Hg or higher blocked the increase in strength and rigidity of the ischaemic myocardium. CONCLUSIONS: It appears likely that in a functioning heart cardiomyocyte contracture in an ischaemic zone can only develop during the diastolic phase. A decrease in diastolic duration and/or an increase in diastolic pressure in the left ventricle may prevent increases in strength and rigidity of the ventricular wall after an infarct and promote the development of aneurysm and possible cardiac rupture. PMID- 8348579 TI - Acute effects of ethanol on cardiac function and intracellular calcium in perfused rat heart. AB - OBJECTIVE: The aim was to evaluate effects of ethanol on cardiac function and intracellular Ca2+ ([Ca2+]i) in perfused rat hearts. METHODS: A Langendorff perfused rat heart preparation was used. Changes in [Ca2+]i were evaluated by surface fluorometry in hearts loaded with Indo 1-AM. RESULTS: Clinically relevant concentrations of ethanol (0.2 or 0.4% vol/vol) had no significant haemodynamic effects. High concentrations of ethanol (1, 2, 3, and 4% vol/vol) showed dose dependent decreases in developed pressure and the systolic peak and overall amplitude of the Indo 1 fluorescence transients (identical to [Ca2+]i), that were partially antagonised by high extracellular Ca2+ ([Ca2+]o = 4 mM). The ethanol concentrations that decreased developed pressure by 50% were 1.4 and 2.6% in the low (1.5 mM) and high [Ca2+]o, respectively. Four per cent ethanol decreased the amplitude of Indo 1 fluorescence transients to 54.5(SD 3.1) and 64.6(7.9)% of control values in the low and high [Ca2+]o, respectively. A relationship between the amplitude of Indo 1 fluorescence and developed pressure was fitted to a single sigmoid curve irrespective of [Ca2+]o. During ethanol washout, there was a dose dependent overshoot of the fluorescence ratio. CONCLUSIONS: Only high concentrations of ethanol depressed left ventricular function in a dose dependent manner by decreasing the amplitude of [Ca2+]i transients. High [Ca2+]o partially antagonised acute alcoholic cardiac depression by increasing the amplitude of [Ca2+]i transients. [Ca2+]i is a mediator of the acute cardiac effects of ethanol in perfused intact rat hearts. PMID- 8348580 TI - Differential regional responses of myocardial interstitial noradrenaline levels to coronary occlusion. AB - OBJECTIVE: The aim was to investigate the influence of coronary occlusion on myocardial interstitial noradrenaline levels in the ischaemic and non-ischaemic regions, using the dialysis technique. METHODS: In nine anaesthetised cats, regional ischaemia was produced by occlusion of the left anterior descending coronary artery for 90 min. Using the dialysis technique, dialysates were sampled from both the ischaemic region and the nonischaemic left circumflex coronary artery region. Dialysate noradrenaline concentrations, as an index of myocardial interstitial noradrenaline content, were measured by high performance liquid chromatography. Myocardial blood flows in the ischaemic and non-ischaemic regions were measured by the hydrogen clearance method. RESULTS: In the non-ischaemic region, neither myocardial blood flow nor dialysate noradrenaline concentration showed significant change. In the ischaemic region, myocardial blood flow decreased significantly, from 117(SEM 12) at control to 23(3) ml.min-1 x 100 g-1, and dialysate noradrenaline concentration increased significantly, from 56.8(4.5) pg.ml-1 at control to 528.8(155.4) pg.ml-1 at 0-30 min of occlusion, 4212.0(1447.7) pg.ml-1 at 30-60 min, and 4179.8(1668.5) pg.ml-1 at 60-90 min. At 0-30 min of the reperfusion period, dialysate noradrenaline concentration in the postischaemic region decreased significantly to 420.2(152.1) pg.ml-1. CONCLUSIONS: Coronary occlusion increased myocardial interstitial noradrenaline levels in the ischaemic region, but not in the non-ischaemic region. PMID- 8348581 TI - Parasympathetic control of cycle length dependence of endocardial ventricular repolarisation in the intact feline heart during steady state conditions. AB - OBJECTIVE: Parasympathetic modulation of the rate dependence of ventricular repolarisation in vivo during steady state conditions was investigated by analysing the effects of removing vagal activity in three groups of anaesthetised cats. METHODS: Bilateral vagotomy was performed while different levels of background sympathetic tone were present in the control periods of each group: in group 1 (n = 6), cardiac sympathetic nerves were intact; in group 2 (n = 7), bilateral stellate ganglionectomy was performed; and in group 3 (n = 7), beta adrenergic blockade (propranolol, 0.5 mg.kg-1) was performed after stellate ganglionectomy. The duration of a left ventricular endocardial monophasic action potential (APD) was measured during atrial pacing at 7-10 cycle lengths (CL). The APD/CL relation was fitted to a hyperbolic function: APD = CL/[(axCL)+b]. Two parameters were considered: APDmax (1/a, ie, APD extrapolated at infinite cycle length, a rate-independent measure of APD) and CL50 (bxAPDmax, ie, the cycle length at which 50% of APDmax is reached). RESULTS: In control conditions, APDmax and CL50 were longer in groups 2 and 3, when cardiac sympathetic effects were reduced or absent. Vagotomy reduced APDmax and CL50 similarly in groups 1 and 2 (APDmax, -24% and -18%; CL50, -36% and -27%) (p < 0.05 v control). In group 3, vagotomy did not affect APDmax and CL50. CONCLUSIONS: No direct parasympathetic influence on the rate dependence of endocardial ventricular repolarisation was observed. The vagal modulation of sympathetic effects may take place either through vago-sympathetic reflexes or via the antagonism of circulating catecholamines distal to the beta receptor. PMID- 8348582 TI - Production of chronic congestive heart failure by rapid ventricular pacing in the rabbit. AB - OBJECTIVE: The aim was to produce a model of low output congestive heart failure by rapid pacing in rabbits. METHODS: To perform rapid pacing in rabbits, a custom made pacemaker was developed which is light (about 80 g) and can pace at up to 400 beats.min-1 for more than two weeks. A thoracotomy was done and two electrodes were sutured onto the left ventricle. A central venous pressure line was chronically implanted. With the use of this pacemaker, rabbits were paced at 350-400 beats.min-1 for several weeks. RESULTS: Central venous pressure increased from 1.4(SEM 0.2) to 6.4(0.5) mm Hg (p < 0.01, n = 14). After pacing for 16.1(1.6) d, haemodynamic studies were performed under anaesthesia with thiamylal sodium. Left ventricular end diastolic pressure was higher in the paced rabbits (n = 10) than in the control rabbits which underwent sham operation but were not paced (n = 6), at -0.6(0.6) v 19.3(2.0) mm Hg (p < 0.01). Cardiac output [673(56) v 536(45) ml.min-1, p < 0.10] and +dP/dt [1433(97) v 722(51) mm Hg.s-1, p < 0.01] were lower in the paced rabbits (n = 7-8) than in the control rabbits (n = 6). The paced rabbits had more ascites [1.9(1.0) v 45.9(18.9) ml, p < 0.05] and pleural effusion [0.4(0.3) v 12.9(6.7) ml, p < 0.10] than control rabbits. Plasma noradrenaline was higher in the paced rabbits (n = 11) than in the control rabbits (n = 7), at 1.59(0.43) v 0.60(0.05) ng.ml-1 (p < 0.05). The ratio of wet heart weight or lung weight to body weight was higher (p < 0.01) in the paced rabbits than in the control rabbits. CONCLUSIONS: Chronic biventricular congestive heart failure can be produced in rabbits by rapid pacing. PMID- 8348583 TI - Velocity profiles and phasic flow patterns in the non-stenotic human left anterior descending coronary artery during cardiac surgery. AB - OBJECTIVE: The aim was to investigate the phasic characteristics of normal human left coronary artery flow and velocity profiles across the vessel. METHODS: The phasic characteristics of flow in the human left anterior descending coronary artery, the centreline flow velocities, and the velocity profiles were measured in 10 patients during corrective surgery for atrial septal defect after closure of the defect. None of these patients had any detectable coronary artery stenosis or left ventricular hypertrophy. Measurements were made with a 20 MHz 80 channel pulsed Doppler velocimeter. RESULTS: The velocity waveform displayed a diastolic predominant pattern with a systolic to diastolic velocity ratio of 0.29(SD 0.17). Reverse flow was observed in early systole in five patients and in mid to late systole in six patients. The values of peak Reynolds number, unsteadiness parameter, and pulsatility index were 504(198), 2.5(0.6), and 5.9(4.4) respectively. The velocity profiles during diastole showed considerable variability in shape, ranging from symmetrical to skewed to M shaped patterns. The peak wall shear rate was 765(250) s-1 on the epicardial wall of the vessel and 712(301) s-1 on the myocardial wall; the difference was not statistically significant. CONCLUSIONS: The velocity waveform displayed a diastolic-predominant pattern. Considerable variability in shape of the velocity profile was found and was perhaps due to the time evolution of the velocity profile within the diastolic time period. PMID- 8348584 TI - Non-invasive assessment of ventricular damage in rats with myocardial infarction. AB - OBJECTIVE: The aim was to evaluate whether two dimensional echocardiographic/Doppler (echo/Doppler) techniques could be used to detect left ventricular damage rapidly, accurately, and non-invasively in rats with a myocardial infarction. METHODS: Female Wistar rats were initially subjected to either a sham operation or surgery to induce a myocardial infarct by ligating the left main coronary artery. Following a minimum of six weeks to recover from the surgery, all rats were re-anaesthetised and cardiac and stroke indexes were determined at similar heart rates, using echo/Doppler techniques. Postmortem histological assessment of myocardial infarct size was compared with the non invasive detection of left ventricular wall motion abnormalities, left ventricular dilatation, and the presence of a left ventricular aneurysm found in the living animal. RESULTS: Rats with myocardial infarction (n = 8) showed a 33(SEM 4)% reduction (p < 0.01) in cardiac index (due to a 33% reduction in stroke index) when compared to their non-infarcted counterparts (n = 5). In addition, a significant correlation (r = 0.84; n = 25; p < 0.01) was found between the assessment of left ventricular damage via non-invasive echo/Doppler measurements and the histological determination of infarct size. CONCLUSIONS: These results support the conclusion that two dimensional echo/Doppler techniques can be used to estimate rapidly and non-invasively the degree of left ventricular damage produced in living rats with myocardial infarction when compared to non infarcted controls. PMID- 8348585 TI - Electrophysiological and inotropic effects of H 234/09 (almokalant) in vitro: a comparison with two other novel IK blocking drugs, UK-68,798 (dofetilide) and E 4031. AB - OBJECTIVE: The aim was to compare the electrophysiological and inotropic effects of the novel class III agents H 234/09, UK-68,798, and E-4031 in vitro. METHODS: The electrophysiological effects were investigated by recording transmembrane action potentials in the isolated ventricular muscle and Purkinje fibres of the rabbit; effects on force (adjusted to the maximum isoprenaline response) and refractoriness were investigated in the isolated cat papillary muscle. RESULTS: It was shown that all the drugs induced a concentration dependent prolongation of the action potential duration, which was much more pronounced in the Purkinje fibres than in the ventricular muscle. However, when compared at concentrations giving a 15% increase of the action potential duration in ventricular muscle, H 234/09 was significantly less effective in the Purkinje fibres than the other two drugs. In the cat papillary muscle all drugs induced an increase in force development. This increase tended to parallel the increase in effective refractory period. However, at prolongations of effective refractory period of more than approximately 50% the increase in developed force levelled off. CONCLUSIONS: All the class III agents investigated showed a positive inotropic effect, which may be of advantage when compared to conventional class I antiarrhythmic agents, which have cardiodepressant actions. Compared to UK-68,798 and E-4031, H 234/09 showed a less unfavourable profile in terms of dispersion of repolarisation, which theoretically may reduce the risk of arrhythmias associated with delayed repolarisation. However, this less unfavourable profile must, like the positive inotropic effect, ultimately be investigated in clinical trials. PMID- 8348586 TI - Estimation of left ventricular elastance without altering preload or afterload in the conscious dog. AB - OBJECTIVE: The aim was to determine the slope (EES) of the left ventricular end systolic pressure-volume line (ESPVL) without altering preload or afterload in conscious dogs. METHODS: Dogs (n = 10) were instrumented to determine left ventricular volume from ultrasonic left ventricular internal dimensions, and to measure left ventricular pressure using a micromanometer. Studies were performed one to two weeks after instrumentation while the animals were conscious. ESPVL was determined from variably loaded left ventricular pressure-volume (P-V) loops generated by the vena caval occlusion. Contractile state was increased by intravenous dobutamine (8 micrograms.kg-1 x min-1) and decreased by intravenous verapamil (10 mg) given after autonomic blockade. From a single normally ejecting beat, we calculated EES-single beat (mm Hg.ml-1) as peak isovolumetric pressure (Pmax) minus end systolic pressure divided by stroke volume. Sunagawa's technique was used to estimate Pmax by fitting the pressure during the isovolumetric contraction and relaxation as: P(t) = 1/2 X Piso[1-cos(omega t+c)]+LVEDP, where Piso = peak isovolumetric developed pressure, LVEDP = left ventricular end diastolic pressure, c = constant accounting for variations in phase angle, and omega = 2 pi/T in which T is duration of contraction. RESULTS: After dobutamine, EES increased, from 8.9(SEM 0.8) to 12.5(1.0) mm Hg.ml-1 (p < 0.05), and EES single beat increased from 9.1(0.9) to 12.0(1.4) mm Hg.ml-1 (p < 0.05). Conversely, after verapamil, EES decreased, from 11.1(1.2) to 6.3(1.1) mm Hg.ml 1, (p < 0.05), and EES-single beat also decreased, from 9.6(1.0) to 7.3(1.2) mm Hg.ml-1, (p < 0.05). CONCLUSIONS: EES calculated from one beat is similar to EES determined from variably loaded left ventricular loops and responds appropriately to inotropic stimulation. This technique provides a reasonable method to calculate EES from left ventricular pressure and stroke volume without altering preload or afterload. PMID- 8348587 TI - Differences in ischaemia tolerance between hypertrophied hearts of adult and aged spontaneously hypertensive rats. AB - OBJECTIVE: The aim was to examine differences between the postischaemic functional and biochemical recovery of adult and aged hypertrophied hearts. METHODS: Isolated hypertrophied hearts of adult and aged spontaneously hypertensive rats (SHRadult; SHRaged) and normal hearts of age matched Wistar Kyoto rats (WKYadult; WKYaged) were perfused in an ejecting heart preparation. Haemodynamic function was monitored before and after 45 min of ischaemia. Coronary effluent samples and tissue biopsies were taken for biochemical analysis. RESULTS: After ischaemia, in SHRadult and WKYadult the maximum positive first derivative of the left ventricular pressure (dP/dtmax) was restored to 105% and 97% respectively of the preischaemic values. Left ventricular developed pressure recovered to 80% (SHRadult) and 97% (WKYadult), while cardiac output reached 71% (SHRadult) and 99% (WKYadult) of preischaemic levels. In SHRaged and WKYaged the dP/dtmax recovered to 26% and 60% respectively (both p < 0.05 compared to the preischaemic values). The left ventricular developed pressure recovered to 36% in SHRaged and to 73% in WKYaged (both p < 0.05), while cardiac output was restored to 6% in SHRaged and 38% in WKYaged (both p < 0.05). Throughout reperfusion, left ventricular end diastolic pressure remained significantly elevated in SHRaged, and was associated with a prominent subendocardial underperfusion, suggesting an impaired diastolic functional recovery. Overall haemodynamic recovery was significantly better in the WKYaged than in the SHRaged. The preischaemic total adenine nucleotides content was comparable in all groups, but creatine phosphate levels were significantly lower in both aged groups than in adult groups. In all but the WKYadult, the total adenine nucleotides were depressed upon reperfusion, while creatine phosphate normalised, except in SHRaged. SHRaged lost more lactate dehydrogenase and tended to lose more xanthine and uric acid than other groups. CONCLUSIONS: The aged hypertrophied heart shows a higher vulnerability to ischaemic damage than the adult hypertrophied heart. This phenomenon is associated with subendocardial underperfusion, increased membrane damage and inadequate recovery of creatine phosphate levels. PMID- 8348588 TI - Increased fibrinolytic activity in the intima of atheromatous coronary arteries: protection at a price. AB - OBJECTIVE: The aim was to quantify and compare the fibrinolytic activity of normal blood vessels (saphenous vein, internal mammary artery, and aorta) and atheromatous arteries (coronary endarterectomy specimens). METHODS: Fibrinolytic activity was measured by fibrin plate and colorimetric assays on fresh samples of coronary endarterectomy core, internal mammary artery, human aorta, and saphenous vein from patients undergoing coronary artery bypass surgery. RESULTS: Fibrinolytic activity on fibrin plates ranked in the order endarterectomy cores > internal mammary artery > saphenous vein. The increased activity of endarterectomy cores was associated with an increased content of extractable tissue plasminogen activator and was suppressed by monoclonal antibody to tissue plasmogen activator. Paired comparisons of tissues from the same patients confirmed this increased activity in endarterectomy specimens relative to normal artery or vein. Urokinase activity was also increased in some endarterectomy specimens, but was more variable than tissue plasmogen activator. CONCLUSIONS: The increased fibrinolytic activity of endarterectomy cores may help preserve patency in atheromatous vessels, but at the possible price of increased intimal instability and fibrous proliferation. PMID- 8348589 TI - Eponyms and acronyms. PMID- 8348590 TI - Alternative splicing generates diversity of VD1/RPD2 alpha peptides in the central nervous system of Lymnaea stagnalis. AB - 1. Two giant peptidergic neurons, VD1 and RPD2, of the visceral ganglion and right parietal ganglion of Lymnaea stagnalis, respectively, play an important role in the modulation of complex physiological and behavioral adjustments that occur as a result of changes in O2 availability. 2. By cDNA cloning, we have identified two types of VD1/RPD2 transcripts expressed in VD1 and RPD2. In addition, these transcripts are also expressed in other neurons. 3. Both transcripts encode distinct yet related VD1/RPD2 preprohormones that may be cleaved to yield distinct but overlapping sets of neuropeptides. 4. Using the polymerase chain reaction technique, we could show the existence of additional splice variants. 5. Analysis of the organization of the VD1/RPD2 gene indicates that the alpha peptide coding region is interrupted by a number of introns. 6. We concluded that the mRNA segment encoding the alpha peptide domain of the VD1/RPD2 preprohormones is alternatively spliced, thus generating different alpha peptides. PMID- 8348592 TI - The effect of osmotic gradients on the outward potassium current in dialyzed neurons of Helix pomatia. AB - 1. The effect of outward and inward water flows through the membrane on outward potassium currents of dialyzed Helix pomatia neurons was studied. 2. An outward water flow increased the peak and sustained outward potassium currents and accelerated the kinetics of their activation. An inward water flow had quite opposite effects--it decreased the peak and sustained potassium currents and delayed the kinetics of their activation. 3. The analysis of the effect of water flow on the conductance of potassium channels showed that an outward water flow increased both the potassium conductance at a given potential (gk) and the maximum potassium conductance (gkmax). An inward water flow again had the opposite effect--it decreased the potassium conductance at given potential and the maximum potassium conductance. 4. Neither an outward nor an inward water flow significantly affected the fraction of open potassium channels at a given potential [n infinity(V)]. 5. These data suggest that in dialyzed neurons the changes of outward potassium current during water flow through the membrane are due mainly to the changes in single-channel conductance and the time constant of current activation. PMID- 8348591 TI - Functional domains on chemically modified tau protein. AB - 1. Neurofibrillary tangles present in Alzheimer's disease and, in a lower proportion, in aged brains are formed mainly by paired helical filaments. The microtubule-associated protein tau is a major structural component of these filaments. In order to increase our understanding of the aberrant behaviour of tau protein leading to its assembly into paired helical filaments, studies were carried out using chemical modifications of brain tau protein. 2. Selective carbamoylation of tau with KCNO resulted in an irreversible modification of lysine residues on tau protein. The capacity of chemically modified tau protein to induce tubulin assembly, under standard in vitro microtubule polymerization conditions, decreased gradually in relation to the increase in concentration of the modifying reagent. 3. Interestingly, carbamoylated tau protein exhibited the capacity to self-assemble into polymeric structures resembling those of paired helical filaments, after incubating the modified protein at concentrations higher than 1.0 mg/ml, at 37 degrees C with KCNO. 4. The nature of polymers obtained from cabamoylated tau protein was analyzed by ultrastructural studies. The data provide new clues toward our understanding of the anomalous interactions of tau in Alzheimer's disease. PMID- 8348593 TI - Management of typical and dysplastic pulmonic stenosis, uncomplicated or associated with complex intracardiac defects, in juveniles and adults: use of percutaneous balloon pulmonary valvuloplasty with eight-month hemodynamic follow up. AB - To alleviate large fixed right ventricular (RV) outflow gradients, percutaneous balloon dilatation of pulmonic stenosis (PS) was performed in 38 patients with mean age of 14 +/- 14 years (median: 9 years, age range: 9 months to 63 years). There were 21 males and 17 females. Thirty-four patients had typical PS (5 of them also having other complex congenital cardiac anomalies, while 13 additional patients had a patent foramen ovale); 2 further subjects had subpulmonic, and 2 dysplastic pulmonary valvular obstructions. Sixteen patients were in the New York Heart Association (NYHA) Class I, 15 in Class II, 6 in Class III, and 1 in Class IV. Electrocardiographic (ECG) evidence of right ventricular hypertrophy (RVH) was present in 29 patients (76%); 3 patients had right bundle branch block (RBBB). For the entire group, there was a marked decrease in the mean systolic transpulmonic gradient in the immediate post-valvuloplasty period (from 97 +/- 43 to 26 +/- 17 mmHg; P < 0.0001). One patient expired 8 hours post-valvuloplasty (he was in the NYHA Class IV, and had severe RV failure). No other cardiovascular complications were encountered; the median hospital stay was 3 days (range: 1-10 days). At an 8-month follow-up, 12 patients who were reevaluated invasively had a median transpulmonic gradient of 27 mmHg (range: 5-92 mmHg) as compared to their pre-valvuloplasty values of 84 mmHg (range: 49-142 mmHg; P < 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348594 TI - Safety of cardiac catheterization via peripheral vascular grafts. AB - There are few data concerning the complications and technical difficulties encountered when cardiac catheterization is performed using peripheral bypass grafts for vascular access. All cardiac catheterizations performed at our institution from January 1, 1984 to April 1, 1991 were retrospectively reviewed to assess the in-hospital clinical outcomes in patients who had arterial access for catheterization achieved via prosthetic graft puncture. Seventeen procedures had percutaneous puncture of a vascular graft from a total of 2,929 arterial catheterizations performed. The interval from graft placement to catheterization was 7.5 +/- 1.1 years. Arterial sheaths were employed in all cases and corresponded to the catheter size, with 5F systems used in 53% and 7F or larger systems used in the remaining patients. No intraprocedural or postprocedural complications were recognized. Technical difficulties were limited to the inability to selectively cannulate a nondominant right coronary artery in 1 patient. We conclude that percutaneous introduction of an arterial sheath and left heart catheterization via remotely implanted vascular bypass grafts is not associated with an increased risk of procedural complications or technical difficulties. PMID- 8348596 TI - Assessment of thallium scintigraphy and echocardiography during dobutamine infusion for the detection of coronary artery disease. AB - Dobutamine infusion was performed in 16 patients following cardiac catheterization, and non-invasive assessment was performed with thallium SPECT and echocardiography. Dobutamine thallium scintigraphy was abnormal in 93% of patients with significant coronary artery disease. In addition, individual epicardial vessel involvement was identified by a corresponding perfusion defect with 88% sensitivity and 93% specificity. Dobutamine echocardiography revealed segmental wall motion abnormalities in 62% of patients with significant coronary disease. However, in six patients baseline segmental wall motion abnormalities on echocardiography improved during dobutamine infusion. Dobutamine thallium SPECT is a safe and useful test for the detection and localization of coronary artery disease. Dobutamine echocardiography is less useful in screening for coronary disease, but may detect areas of abnormally functioning myocardium having retained viability. PMID- 8348595 TI - Contrast echocardiography during cardiac catheterization in patients with congenital heart diseases. AB - Contrast echocardiography performed during cardiac catheterization has mostly been limited to a few published case reports. We studied 37 patients with congenital heart disease to assess the capability of the method to diagnose cardiac shunts and valve regurgitation. Injections of 5% dextrose in water through an angiographic catheter were made to evaluate septal integrity and valve competence compared with conventional contrast angiography. An overall sensitivity of 93% and specificity of 78% were found. In four cases of atrial septal defect and seven of mitral regurgitation, the sensitivity was 100%. It was slightly lower for eleven cases of ventricular septal defect (91%) and four of patent ductus arteriosus (75%). When assessing aortic, tricuspid and pulmonary valve competence, the method proved to be more sensitive than conventional angiography to detect mild regurgitation. Contrast echocardiography is a sensitive and safe technique that may be used in association with conventional angiography reducing the need for radiographic contrast and ionizing radiation time. PMID- 8348597 TI - Successful directional atherectomy of eccentric renal artery stenosis using the Simpson directional coronary atherocath as a primary therapy. AB - A 67-yr-old female patient with accelerated hypertension, severe peripheral vascular disease, diabetes mellitus, and coronary artery disease had an abnormal renal scan, renal angiogram, and renal vein renin determination with lateralization to the left kidney. Angiography demonstrated a very tight, eccentric plaque obstructing the left renal artery of approximately 99%. Because of the anatomy of the plaque, balloon dilatation was deemed inadvisable. Subsequently, a Simpson 7F graft DCA atherocath through a four-curved 10F right bypass graft guiding catheter was used to successfully debulk the left renal artery. After debulking, the artery was dilated with a 5 mm Meditech balloon on a wire through a Cobra guiding catheter. The patient's blood pressure responded immediately and there were no complications. A large amount of atherosclerotic plaque was removed from the renal artery. PMID- 8348598 TI - A unique scenario for coronary atherectomy. AB - Despite several attempts, balloon angioplasty of a slightly eccentric stenotic lesion in the proximal right coronary artery failed to result in any increase of luminal diameter. Following disruption and partial removal of a fibrous atherosclerotic cap using directional atherectomy, subsequent balloon angioplasty was highly successful. PMID- 8348599 TI - Early stent occlusion is not always caused by thrombosis. AB - Early occlusion of intracoronary stents has been exclusively attributed to thrombosis. Using intracoronary angioscopy, we have found 2 patients in whom this common and serious complication of coronary stenting was caused by obstructive intima dissection rather than thrombosis. PMID- 8348600 TI - Implantation of half Palmaz-Schatz stents in short aorto-ostial lesions of saphenous vein grafts. AB - Two cases are presented in which a half Palmaz-Schatz stent was implanted in a short lesion located in the ostium of a saphenous vein graft. Aorto-ostial stenoses are a technical challenge for balloon angioplasty and stenting. Short stents may offer several advantages as regards deployment, positioning, thrombogenicity, and restenosis. PMID- 8348601 TI - Diagnosis of stenosis in a pulmonary valve-conduit using an angioplasty guide and probing catheter. AB - A 42-year-old man who had undergone previous Blalock-Taussig anastomoses and placement of a homograft aortic valve-root conduit for tetralogy of Fallot presented with dyspnea at rest. Previous catheterization had shown homograft stenosis at the level of the pulmonic valve. Repeat catheterization necessitated the use of angioplasty guide and probing catheters to cross the stenosis, and pullback documented stenoses both across the homografted valve and within the homograft aortic root-native pulmonary artery conduit. PMID- 8348602 TI - Use of translesional coronary flow velocity for interventional decisions in a patient with multiple intermediately severe coronary stenoses. AB - Translesional pressure gradients are currently not performed routinely for most angioplasty procedures because of the technical limitations. With the use of an 0.18 inch Doppler flow velocity guidewire, coronary flow velocity, both proximal and distal to a lesion, can be easily assessed. In branching arteries, significant lesions are characterized by a ratio of proximal to distal flow velocity of > 1.7, loss of the normal phasic diastolic predominant flow velocity pattern, and/or loss of distal hyperemia. We describe the use of coronary flow velocity in assisting important decision making in a young patient with a recent myocardial infarction and multiple coronary lesions. The decision for angioplasty of the hemodynamically significant stenosis was confirmed by translesional flow velocity measurements. A rational approach to coronary intervention in patients with multiple stenoses of intermediate severity appears to be facilitated by direct measurement of translesional flow dynamics. PMID- 8348603 TI - Aortic dissection with aortopulmonary artery fistula. AB - A case of aortic dissection complicated by aortopulmonary artery fistula is reported. Aggressive diagnostic and surgical management was associated with a favorable, long-term outcome. PMID- 8348604 TI - Double-lumen catheter assessment of aortic stenosis: comparison with separate catheter technique. AB - Hemodynamic assessment of aortic stenosis in the catheterization laboratory accurate determination of the transvalvular gradient. A commercially available double-lumen pigtail catheter can be used to obtain this gradient via a single arterial puncture. The catheter has several advantages over other methods used to measure the gradient in aortic stenosis, but it has not been critically evaluated. In order to assess the performance of this catheter compared to the traditional standard of separate catheters above and across the aortic valve, we studied 10 patients with aortic stenosis using both catheter systems. Aortic valve areas ranged from 0.34 cm2 to 1.1 cm2. Linear regression analysis confirmed excellent correlation between the two methods in measurement of the mean transvalvular gradient (r = 0.98) and calculation of the aortic valve area (r = 0.99) using the Gorlin formula. We conclude that the double-lumen pigtail catheter provides accurate data in the hemodynamic evaluation of aortic stenosis. PMID- 8348605 TI - Endoluminal sealing of vascular wall disruptions with radiofrequency-heated balloon angioplasty. AB - Suboptimal luminal widening or acute closure secondary to arterial dissection remain significant risks of percutaneous transluminal balloon angioplasty. Non surgical techniques are often employed in an attempt to repair dissections either as temporary or definitive treatment. The aim of this study was to test the hypothesis that radiofrequency thermal balloon angioplasty at an operating temperature of 70 degrees C and low inflation pressure could seal dissections and perforations in a model of severe arterial wall damage. Dissections and perforations were created in renal (n = 4) and carotid (n = 4) arteries in four mongrel dogs. Endoluminal sealing was then attempted with conventional balloon angioplasty or radiofrequency thermal balloon angioplasty (2 atm at 70 degrees C). Contrast dye extravasation persisted in all cases following conventional balloon angioplasty but completely resolved with radiofrequency balloon angioplasty in all but one artery. Histologic examination of the arteries treated with radiofrequency balloon angioplasty showed extensive thermal injury, including transmural coagulation necrosis, flattening of the internal elastic lamina, and medial thinning. On the basis of these results, the utility of thermal balloon angioplasty for endoluminal sealing of dissections and perforations complicating angioplasty deserves further evaluation. PMID- 8348606 TI - Initial experience with a new balloon-on-a-wire catheter: the Bijou. AB - This paper presents our initial experience with a new low-profile balloon "on-a wire" catheter, the Bijou. The concept of this balloon is to provide an additional side lumen with the advantages of (1) the ability to measure pressure gradient, (2) the possibility of drug infusion, and (3) the ability to advance a steerable guidewire through this side lumen. The balloon has been tested in 15 patients; 14 underwent an elective procedure for stable angina pectoris (with 2 cases of restenosis) and one an emergency angioplasty in a case of acute myocardial infarction. The stenosis was located on the left anterior descending artery in 11 procedures, on the right in 3, on a marginal branch in 2, on the circumflex and a saphenous vein graft in 1. All stenoses could be dilated successfully (residual stenosis < 25%). The transstenotic pressure gradient felt from 49 +/- 13 mmHg to 7 +/- 4 mm Hg after angioplasty. Except for an uncomplicated dissection in 3 patients, no other complication was noted. With this new catheter, the double-lumen configuration adds the advantages of an "over the-wire" to an "on-a-wire" system. PMID- 8348607 TI - The use of a new wire in a 6-year-old coronary artery occlusion: the Jagwire recanalization guidewire. AB - Chronic total occlusions are difficult to treat, usually because they cannot be crossed with a guidewire or dilating catheter. A variety of angioplasty systems designed to facilitate coronary angioplasty of chronic total occlusions have been used. We report the case of a 6-year-old occlusion of the right coronary artery that was treated with the Jagwire, a new guidewire designed for use in challenging lesions. This device successfully crossed the lesion and resulted in a successful angioplasty. The patient's angina dramatically improved following the procedure. PMID- 8348608 TI - Caveat emptor: a clinician's guide to assessing the physiologic significance of arterial stenoses. PMID- 8348609 TI - Pulmonary valvuloplasty in adults using the Inoue balloon catheter. AB - This report describes a new balloon pulmonary valvuloplasty technique using the Inoue balloon catheter performed in 14 consecutive adult patients, aged 17-47 years (mean 27). The mean right ventricular systolic pressure and the pulmonary valvular peak-to-peak systolic gradient decreased from 102 +/- 41 to 52 +/- 19 mm Hg (p = 0.001) and 81 +/- 40 to 7 +/- 7 mm Hg (p = 0.0002), respectively. An infundibular peak-to-peak systolic gradient either developed (n = 13) or increased (n = 1). None of the patients were treated with beta-adrenergic blockers before or after the valvuloplasty. Eight patients underwent repeat hemodynamic study 12-30 months (mean 17) after treatment, and had no evidence of valvular restenosis. The mean right ventricular systolic pressure and the mean infundibular peak-to-peak systolic gradient decreased, compared to the values immediately after valvuloplasty (54 to 40 mm Hg, p = 0.03, and 28 to 10 mm Hg, p = 0.03, respectively). The study suggests that pulmonary valvuloplasty in adults using the Inoue balloon catheter technique is feasible, safe, and effective. PMID- 8348610 TI - Processed Vg1 protein is an axial mesoderm inducer in Xenopus. AB - Vg1 is a TGF beta-related growth factor encoded by a maternal mRNA localized to vegetal blastomeres in Xenopus embryos. Vg1 precursor protein is abundant in vegetal cells, but the processed mature form has not been readily detected and no activity has been demonstrated for the putative Vg1 mature protein. We have engineered a BMP2-Vg1 fusion (BVg1) that promotes formation of mature Vg1 protein in vivo. Injection of BVg1 mRNA induces dorsal mesoderm in animal cap cells, and BVg1 expression in ultraviolet-ventralized embryos fully restores a normal dorsal axis. Blastomeres expressing BVg1 act as a Nieuwkoop center, the region that induces the Spemann organizer. our results lead us to suggest that localized posttranslational processing of Vg1 precursor protein on the future dorsal side of the embryo is a key step in generating dorsal mesoderm and the body axis in Xenopus. PMID- 8348611 TI - The maternal gene skn-1 encodes a protein that is distributed unequally in early C. elegans embryos. AB - The autonomous or cell-intrinsic developmental properties of early embryonic blastomeres in nematodes are thought to result from the action of maternally provided determinants. After the first cleavage of the C. elegans embryo, only the posterior blastomere, P1, has a cell-intrinsic ability to produce pharyngeal cells. The product of the maternal gene skn-1 is required for P1 to produce pharyngeal cells. We show here that the Skn-1 protein is nuclear localized and that P1 appears to accumulate markedly higher levels of Skn-1 protein than its sister, the AB blastomere. We have examined the distribution of Skn-1 protein in embryos from mothers with maternal-effect mutations in the genes mex-1, par-1, and pie-1. These results suggest that mex-1(+) and par-1(+) activities are required for the unequal distribution of the Skn-1 protein and that pie-1(+) activity may function to regulate the activity of Skn-1 protein in the descendants of the posterior blastomere P1. PMID- 8348612 TI - Macrophages are required for cell death and tissue remodeling in the developing mouse eye. AB - To identify and characterize tissue remodeling processes mediated by macrophages, we have generated transgenic mice in which diphtheria toxin is expressed from a macrophage-specific transgene. Expression of the transgene disrupts subsets of mature macrophages in both the eye and the peritoneal cavity and results in the persistence of two normally transient ocular tissues, the hyaloid vasculature and the pupillary membrane. Furthermore, the cells comprising the pupillary membrane appear alive up to 14 days after the structure is normally remodeled, suggesting that the macrophage actively elicits target cell death. Thus, these transgenic mice provide direct evidence for the active involvement of macrophages in developmentally programmed tissue remodeling and identify the hyaloid vessels and the pupillary membrane in the eye as targets of macrophage-mediated remodeling. PMID- 8348613 TI - Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. AB - The wee1 tyrosine kinase and cdc25 tyrosine phosphatase of fission yeast play antagonistic roles in the induction of mitosis through cdc2 regulation. We show here that the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis in cells expressing otherwise catastrophic levels of cdc2 activators. Paradoxically, wee1-rescued cells display very high levels of mitotic cdc2 kinase activity. We account for this anomaly by our observation that the cdc2 activator, cdc25C, is a cytoplasmic protein that, like cyclin B1, enters the nucleus at the G2/M transition. Thus, cdc2 is likely to be activated in the cytoplasm and requires nuclear localization to initiate both cytoplasmic and nuclear mitotic transformations. The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase. PMID- 8348614 TI - tRNA as a positive regulator of transcription antitermination in B. subtilis. AB - Most Bacillus tRNA synthetase genes are regulated by a common transcription antitermination mechanism but respond individually to limitation for the cognate amino acid. The mRNA leader regions of these genes exhibit extensive structural conservation, with a single codon specific for the appropriate amino acid at the identical position in each structure. Alteration of this sequence in the tyrS gene from UAC (tyrosine) to UUC (phenylalanine) resulted in loss of induction by tyrosine limitation and a switch to induction by phenylalanine limitation. Insertion of an extra base immediately upstream of the codon did not alter regulation, indicating a nontranslational mechanism. A nonsense codon resulted in an uninducible phenotype that was suppressible in a lysyl-tRNA nonsense suppressor mutant, indicating that tRNA acts as an effector. PMID- 8348615 TI - The mitochondrial receptor complex: a central role of MOM22 in mediating preprotein transfer from receptors to the general insertion pore. AB - The receptor complex in the mitochondrial outer membrane, which consists of at least seven different proteins, is responsible for the recognition and translocation of cytosolically synthesized preproteins. Two of its subunits, MOM19 and MOM72, function as surface receptors for preproteins. Four other subunits (MOM38, MOM30, MOM8, and MOM7) have been suggested to constitute the general insertion pore (GIP). Here we report on the structure and function of MOM22. MOM22 is anchored in the outer membrane by a single transmembrane segment. The highly negatively charged N-terminal domain is exposed to the cytosol and the C-terminal domain to the intermembrane space. MOM22 appears to be a central component of the receptor complex, required for the transfer of preproteins from the receptors to the GIP. We speculate that the negatively charged domain of MOM22 is involved in the transfer of positively charged signal sequences of preproteins. PMID- 8348616 TI - Nuclear export of proteins: the role of nuclear retention. AB - Proteins that shuttle between nucleus and cytoplasm are implicated in transport and signal transduction processes. Using assays based on interspecies heterokaryons and microinjection of Xenopus oocytes, we examined what structural features determine nuclear export of shuttling proteins. Three classes of proteins were studied: first, wild-type and mutant forms of nucleolin, one of the first shuttling proteins identified; second, artificial nuclear reporter proteins derived from cytoplasmic pyruvate kinase; and third, wild-type and mutant lamins differing in their abilities to be incorporated into the lamina. Our results show that a protein does not require positively acting export signals to be transported from nucleus to cytoplasm; instead, its shuttling ability is limited primarily by intranuclear interactions. We conclude that nucleocytoplasmic shuttling is a general phenomenon not restricted to proteins involved in nucleocytoplasmic transport. PMID- 8348617 TI - A 5' element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. AB - We have characterized an element near the 5' boundary of the chicken beta-globin domain that insulates a reporter gene from the activating effects of a nearby beta-globin locus control region (5'HS2) when assayed in the human erythroid cell line K562. We show that the insulation mechanism is directional, that it operates at the level of transcription, and that it involves the alteration of chromatin structure over the promoter of the gene. The insulator has no significant stimulatory or inhibitory effects of its own. In transgenic Drosophila, the insulator protects the white minigene from position effects. The action of the insulator thus is not restricted to erythroid or mammalian cells, suggesting that such elements may serve an important and widely distributed function in the organization of chromatin structure. PMID- 8348618 TI - Odorant-selective genes and neurons mediate olfaction in C. elegans. AB - Olfaction is a versatile and sensitive mechanism for detecting volatile odorants. We show that the nematode C. elegans detects many volatile chemicals, which can be attractants, repellents, or attractants at low concentrations and repellents at high concentrations. Through laser ablation, we have identified chemosensory neurons that detect volatile odorants. Chemotaxis to volatile odorants requires different sensory neurons from chemotaxis to water-soluble attractants, indicating that C. elegans might have senses that correspond to smell and taste, respectively. Single neurons have complex sensory properties, since six distinguishable volatile odorants are sensed by only two types of sensory neurons. Chemotaxis to subsets of volatile odorants is disrupted by mutations in the odr genes, which might be involved in odorant sensation or signal transduction. PMID- 8348619 TI - Epidermal growth factor-induced actin remodeling is regulated by 5-lipoxygenase and cyclooxygenase products. AB - In a number of cell types, epidermal growth factor (EGF) evokes dramatic morphological changes, cortical actin polymerization, and stress fiber breakdown. The molecular processes by which increased EGF receptor tyrosine kinase activity results in actin reorganization and morphological changes are unresolved. Recently, we demonstrated that arachidonic acid metabolites function in EGF signal transduction. We now report that in A431 cells, HeLa cells, and rat-1 fibroblasts, the EGF-induced cortical actin polymerization is produced by lipoxygenase metabolism, whereas in these cells stress fiber breakdown is mediated by cyclooxygenase metabolites. Also, the EGF-provoked rounding up in A431 cells is dependent on arachidonic acid metabolism. We conclude that leukotrienes and prostaglandins act in concert, as second messengers, to produce morphological effects and actin reorganization, providing a novel mechanism for directing growth factor-induced cytoskeletal changes. PMID- 8348621 TI - [Comparison of 2 methods of detecting slime production by coagulase-negative staphylococci]. AB - In the series of 212 coagulase-negative staphylococci strains isolated from blood cultures, in which the slime production was tested by means of two methods--a method using agar with Congo red and a Christensen method--S. epidermidis, S. haemolyticus and S. hominis were identified most frequently (in 69.3%, 18.4% and 6.6%, respectively). The slime production was detected by both methods in 28 strains (13%) of four species, most often in S. epidermidis (in 17%). By comparing the Congo red agar method with the Christensen method the sensitivity and specificity of the former was determined (85% and 99%, respectively). Thus the Congo red agar method for the detection of slime production by staphylococci seems to be a reliable tool. PMID- 8348620 TI - TAP1-dependent peptide translocation in vitro is ATP dependent and peptide selective. AB - T cells detect infection of cells by recognizing peptide fragments of foreign proteins bound to class I molecules of the major histocompatibility complex (MHC) on the surface of the infected cell. MHC class I molecules bind peptide in the endoplasmic reticulum, and analysis of mutant cells has demonstrated that an adequate supply of peptides requires the presence of two genes in the MHC class II locus that encode proteins called transporters associated with antigen processing (TAP) 1 and 2. TAP1 and TAP2 are members of the ATP-binding cassette family of membrane translocators. In this study, we demonstrate in a cell-free system that TAP1 is part of an ATP-dependent, sequence-specific, peptide translocator. PMID- 8348622 TI - [Identification of reference strains of intestinal bacteria using the TNW, IDENTI and NIS 86 numeric identification systems]. AB - A total of 176 reference strains including 63 species of Enterobacteriaceae mainly of clinical origin were tested by commercial diagnostic kits ENTEROtest 1 & 2. The identification efficacy in both systems TNW and IDENTI was nearly in agreement 144 (81.8%), 142 (80.7%) respectively correctly identified strains. The NIS 86 system identified only 54 (30.7%) strains correctly. PMID- 8348623 TI - [Identification of mycobacteria species using genetic probes]. AB - Using commercially available probes Gen-Probe (Accu-Probe, Epignost, Austria) labelled with acridinium ester, the authors identified 102 cultures of mycobacteria which are the causal agents of classical tuberculosis or cause mycobacterioses which are difficult to control by therapeutic measures. The cultures were isolated from sputum or lymph nodes and cultivated on Lowenstein Jensen medium. The authors proved a 100% sensitivity of the probe for isolates of M. tuberculosis and M. kansasii. In a group of 36 strains sent as suspect M. avium 33 strains reacted with the probe for the M. avium complex, 28 strains with the M. avium probe and 4 strains with the M. intracellulare. One isolate hybridized only with the probe for the M. avium complex. In one isolate a positive hybridization value was recorded with the M. gordonae probe and in one pigmented strain with the M. kansasii probe. One isolate did not hybridize with any of the probes used. In one instance a mixed culture of M. tuberculosis and M. avium was involved. The results of hybridization were interpreted in RLU values (relative light unit). Isolates above 30,000 RLU were evaluated positively, as recommended by the manufacturer. PMID- 8348624 TI - [Determination of IgG toxoplasma antibodies using ELISA with uniform serum dilutions]. AB - The ELISA reaction with uniform serum dilution (1:400) for assessment of toxoplasmatic antibodies class IgG agreed in 100% when compared with commercial kits (VIRELISA and GULL Lab.). Both these tests disagreed with the standard complement fixation reaction in 7.5% of the specimens. This qualitative disagreement was confirmed also in a group of 400 sera where 7.14% of CFR negative specimens reacted positively in the described ELISA reaction. Quantitative correlation of results of CFR and ELISA IgG displays the usual scatter of values. Therefore individual CFR titres cannot be matched unequivocally with titres of optic density and thus it is not possible to assess empirically the stage of infection. To assess the stage of infection it is therefore necessary to make a supplementary assessment of IgM antibodies. In cases detected in time the decision can be based on a rise of IgG values in paired serum specimens examined in one reaction. Dynamics of formation of IgG antibodies and their chronological sequence with IgM antibodies displayed a typical course in patients with clinical toxoplasmosis. The described reaction is the basis of commercially manufactured kits ELISA IgG Toxo Micro II. PMID- 8348625 TI - [Transstadial transmission of Francisella tularensis in the tick, Ixodes ricinus, infected during the larval stage]. AB - Based on previous studies which proved the decisive importance of the degree of bacteraemia of experimentally infected white mice for the degree of infection of ticks Ixodes ricinus the authors confirmed the possibility of transstadial transmission of Francisella tularensis from larvae via nymphs to imagos by the detection of germs in the ticks and by experiments attempting their transmission to white mice. This applied to imagos even one year after the infection of larvae. Transmission was recorded even in imagos which did not transmit the infection in the nymphal stage. F. tularensis was repeatedly detected in the faeces of nymphs and imagos, which along with possible consumption of infected ticks by hosts, indicates further possibilities of transmission of the infection in nature. The results of quantitative examinations of the degree of infection of ticks enable us to conclude that the germs reproduce in the ticks after feeding on the host. PMID- 8348626 TI - [Differentiation of serologic group A streptococci from group C and G using disks with various bacitracin levels]. AB - It was revealed that a diameter of the inhibition zone of 10 mm or more surrounding a disk with 0.04 U bacitracin differentiates reliably strains of the serological group A form strains of group C and G with the exception of 7.3% strains of group C and G with a high susceptibility for bacitracin. The disks with a higher bacitracin content gives less reliable results. PMID- 8348627 TI - [Salmonella osteomyelitis in a 9-month-old infant]. AB - The authors describe a case of salmonella pyarthritis with subsequent osteomyelitis caused by Salmonella enteritidis in a 9-month-old infant. The strain was isolated from punctate drawn from the knee joint. PMID- 8348629 TI - [A case of coccidioidomycosis in Plzen]. AB - A case of the pulmonary form of coccidioidomycosis of a Czech patient infected in Arizona is described. The disease was diagnosed on the basis of serological tests. In addition to a review of the mycological, epidemiological and clinical picture of coccidioidomycosis criteria of laboratory mycological diagnostics are given. It is important to be aware of this mycosis in patients who have a history of recent visits to endemic areas in North, Central and South America. PMID- 8348628 TI - [Changes in the nomenclature of mycoses]. AB - The author gives an account of a report of the Nomenclature Committee of the International Society for Human and Animal Mycology making the present terminology of mycoses more precise and unified. Changes recommended by the Committee are designed to eliminate the instability of currently used terms influenced by new names of mycological taxonomy as well as by clinical aspects and the pathology of mycoses. The essential feature of the changes is a recommendation for fungal disease names not based on the word derived from the taxon of the causative fungal genus but providing, in a narrow or broader way, information on the clinical and pathological entity caused by the fungus. The individual recommendations are supplemented by explanatory examples and a list of accepted and rejected fungal disease names is tabulated. PMID- 8348630 TI - [Lyme borreliosis: review of present knowledge]. AB - The author reviews hitherto assembled knowledge on a bacterial disease, Lyme borreliosis transmitted by ticks. Initial information on Lyme borreliosis appeared at the beginning of the 20th century. In Czechoslovakia attention to the disease was paid since cca 1960. The infection occurs as a rule in the summer months during the period when ticks are parasitic and at that time the causal agent of the disease is transmitted to hosts. Information on the prevalence and incidence of Lyme borreliosis in Europe is not complete and so far we do not possess a standardized diagnostic method for assessment of circulating antibodies in the patients' serum and cerebrospinal fluid. The infectious disease is caused by the gram-negative spirochete Borrelia burgdorferi. The Borrelia cell has a similar morphological structure as cells of other gram-negative bacteria. Chemical analysis of the external membrane of B. burgdorferi revealed the presence of 46% proteins, 51% lipids and 3% carbohydrates. The typical shape of borrelias indicates marked ondulation of 8-14 periplasmatic flagellae along the cell body. Borrelias can be cultivated in vitro in modified Barbour-Stoenner Kelly medium at an optimal temperature of 30-37 degrees C. The change of morphology during cultivation is typical for B. burgdorferi. Clinically Lyme borreliosis is manifested in two stages. A typical manifestation of the early stage is a skin lesion--erythema migrans. The later stage is characterized above all by relapsing arthritis, CNS infection and chronic acrodermatitis chronica atrophicans. The disease is treated by administration of a number of antibiotics either by the oral route or by injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348631 TI - [Treatment of cellular immunodeficiency in diseases requiring surgery]. PMID- 8348632 TI - [Serum sperm antibodies in women hospitalized for threatened abortion]. AB - The authors examined the antispermatozoal activity of 123 sera of patients hospitalized at the Gynaecological and Obstetric Department in Plzen during the 8th-9th week with diagnosis of imminent abortion. They revealed markedly higher antibodies against spermatozoa in particular in IgG, but also in IgA and IgM in 17 (13%) patients, who eventually had spontaneous abortions. The authors investigated also the obstetric history in connection with the presence of antibodies against spermatozoa. The antibody levels were higher in primary pregnant women. PMID- 8348633 TI - [Selective reduction of multiple pregnancy in the 1st trimester: results and experience in 10 cases]. AB - Ten patients with multiple gestations, all resulting from in vitro fertilization, underwent multifoetal pregnancy reduction. In four cases transvaginal puncture was performed, six patients underwent transabdominal pregnancy reduction. Seven women delivered, all three pregnancy losses occurred in the transvaginal punction group--there was one early loss after the procedure and two abortions in the late second trimester. There were 5 sets of twins and two singletons were delivered. Multifoetal pregnancy reduction represents an important addition to the management of unplanned multifoetal pregnancy resulting from infertility treatment. The procedure is not without risks and these must be weighted against expected benefits. PMID- 8348634 TI - [Pharmacologic prevention of postoperative cystitis]. AB - For prevention of postoperative cystitis the authors tested currently used drugs which influence the adherence of bacteria to the urothelium, nitrofurantoin (FurantoinR), 3 x 1 tabl. per day and trimetroprim with clotrimoxazole (BiseptolR), one tablet in the evening before operation. They found that Furantoin reduced the frequency of the inflammation in patients subjected to abdominal operations from 12.3% in the control group to 2.3% and in those subjected to vaginal operations from 46.1% to 9.6%. The disadvantage of the drug is that it must be taken every day and that it is poorly tolerated by the patients. Biseptol is excreted more slowly and therefore 1 tablet before operation blocks the development for a maximum of 48 hours. In patients with abdominal operations the frequency of inflammation was similarly as in controls, 12%, in patients with vaginal operations the number of inflammations declined to 24.5%. Biseptol, 1 tablet before operation, is suitable only in patients where it is not assumed that the catheter will be inserted for a prolonged period. PMID- 8348635 TI - [Association of appendicitis with extra-uterine pregnancy]. PMID- 8348636 TI - [Simultaneous appendectomy and gynecologic surgery]. PMID- 8348637 TI - [The Lyon method of vaginal hysterectomy]. PMID- 8348638 TI - [Retroperitoneal liposarcoma after gynecologic surgery]. PMID- 8348639 TI - [Development and present status of diagnosis of incompetence of the uterine cervix]. PMID- 8348640 TI - [The role of inborn chromosomal aberrations in the etiology of infertility]. PMID- 8348641 TI - [Melatonin and oral contraception]. PMID- 8348642 TI - [History of women's health care in Czechoslovakia. VII]. PMID- 8348643 TI - [Czech senology--origins, traditions, development]. PMID- 8348644 TI - [Maternal hyperphenylalaninemia]. PMID- 8348645 TI - [Is restriction of physical activity indicated in the prevention of retinal detachment?]. AB - The author evaluates the importance of different vitreoretinal factors and the role of indirect injury in the pathogenesis of detachment of the retina/DR/and holds the following view as regards subjects inclined to pursue physical activity. Numerous and frequent vitreoretinal risk factors are a forecast of DR only in a small fraction of patients. Indirect injury is not recognized as a cause of DR. Risk factors incl. medium-grade and high-grade myopia are not an indication for restriction of physical activity nor for Caesarean section in pregnant women. Restriction of physical activity acts as a psychic trauma and does not prevent the development of DR. PMID- 8348646 TI - [Immunologic mechanisms and the effect of immunosuppressive therapy in ophthalmology]. AB - The authors mention some immunopathological mechanisms which participate in the beginning and maintenance of activity in so-called idiopathic endogenous uveitis. They draw attention to the possibility to influence these mechanisms by immunosuppressive treatment, mention its advantages and the feasibility of risk of undesirable side-effects. The authors assume that it is useful to use corticoids and cytotoxic substances as well as the more aimed action on immunity exerted by Cyclosporine A. PMID- 8348647 TI - [Personal experience with immunosuppressive therapy of endogenous uveitis]. AB - The authors investigated 43 patients with the original diagnosis of endogenous idiopathic uveitis for a period of one year. Comprehensive ophthalmological, immunological and rheumatological examination revealed that in all investigated cases either systemic disease was involved or diseases associated with impaired immunity or endogenous idiopathic uveitis. The patients were treated by immunosuppressive therapy either by Prednisone alone or by a combination of Prednisone and Cyclophosphamide. In all instances remission was achieved, contrary to previous therapy employed in these patients. In the majority of patients/21 of 23 and 12 of 18 resp./remission persisted for at least one year. The authors discuss indications and pitfalls of immunosuppressive therapy based on recommendations found in the literature. PMID- 8348648 TI - [Retinal vein occlusion. I. Pathogenesis of circulatory changes]. AB - In the pathogenesis of macular edema in venous occlusion of the retina, the majority of authors considers the high intracapillary pressure to be the decisive factor. The author's explanation is somewhat different and is based on two assumptions. The existence of the vascular autoregulatory mechanisms of the retina and the so-called disproportion between the arterial and the venous volume. When the critical level of the disproportion of the arterial and the venous volume is surpassed, the retinal autoregulation begins to fail which manifests itself by a marked retinal edema and an essential decrease in visual acuity. PMID- 8348649 TI - [Retinal vein occlusion. II. Collateral systems]. AB - During the period of 6-12 months, in the majority of patients with occlusion of the branch of the retinal vein, the macular edema regresses and the intraretinal hemorrhages are resorbed. According to the author, this restoration of the circulatory conditions in the retina takes place especially due to the development of the veno-venous collaterals. The author presents an explanation of the mechanism of the regulation of the circulatory conditions in the retina during the development of the collaterals on the basis of the new approach to the explanation of the pathogenesis of the circulatory changes in occlusion of the branch of the retinal vein. PMID- 8348650 TI - [Retinal vein occlusion. III. Arteriolar constriction]. AB - The author assumes that the process of the adjustment of the disproportion between the arterial and the venous volume can be favourably influenced by a decrease in the offered arterial volume to the venous occluded blood path. This can be achieved by a narrowing of the input arteriole with the help of the method of arteriolar constriction using the argon laser. The author is of the opinion that the method of arteriolar constriction finds its application especially in the treatment of severe prognostically unfavourable forms of occlusion of the branch of the retinal vein with presence of extensive hemorrhages in the retina. In such severe forms of occlusion, the author recommends to apply the arteriolar constriction already in the early acute phase of the disease. PMID- 8348651 TI - [Arteriolar constriction in the treatment of branch retinal vein occlusion. Initial experience]. AB - The authors describe their first experiences in the treatment of 12 eyes with prognostically unfavourable occlusion of the retinal branch of the vein by application of the laser technique of arteriolar constriction. They introduced photocoagulation 1 to 4 weeks after the onset of the occlusion. The resulting visual acuity 6/12 and better was achieved in 83%, the worst resulting acuity 6/18 in 17% two years after onset of the occlusion. In all the eyes, the achieved improvement was approximately by 4 lines of Snellens optotypes. PMID- 8348652 TI - [Local anesthesia in cataract surgery]. PMID- 8348653 TI - [Treatment of microbial eye infections with antibiotics]. PMID- 8348654 TI - [Use of lasers in ophthalmology. I. Laser diagnosis and non-photodisruptive therapy]. PMID- 8348656 TI - [Vision and the military service]. PMID- 8348655 TI - [Use of lasers in ophthalmology. II. Photodisruptive therapy]. PMID- 8348657 TI - [Physical development in patients with acute lymphoblastic leukemia in childhood]. AB - Acute lymphoblastic leukaemia (ALL) is one of the readily treatable neoplastic diseases of childhood. One of the late sequelae of treatment can be impaired growth. The authors followed up therefore a group of 63 patients where during childhood a diagnosis of ALL was made. The investigated group was treated according to two fundamental protocols--according to Pinkel's protocol and according to BMF protocols. All patients treated according to Pinkel's protocol had, as part of prevention of leukaemia of the CNS, radiotherapy of the skull, patients treated according to the BMF protocol only when the risk factor was higher than 0.8. The authors investigated in their patients the height and proportionality after termination of all antileukaemic therapy. They found that the height of children, adolescents and adults who suffered from ALL during childhood is average or less. A tendency towards obesity is typical. The authors did not observe a correlation with the total cumulative doses of cytostatics nor a marked correlation with radiotherapy. Impaired growth was more frequent when ALL was diagnosed before the age of 3 years and where the interval after completed therapy was shorter. PMID- 8348658 TI - [Bacterial meningitis in neonates. Retrospective study 1977-1991]. AB - In 1977-1991 at the Paediatric Clinic in Hradec Kralove 43 neonates with bacterial meningitis (BM) were hospitalized. In 31 (72%) risk factors for the development of perinatal infection were detected. The aetiological agent was proved in 40 neonates, most frequently E. coli (46.5%), Streptococcus agalactiae (16.2%), Proteus (11.6%). In the second half of the investigation period (1984 1991) there was a significantly higher ratio of G+ microorganisms, in particular Streptococcus agalactiae. In three neonates the diagnosis of BM was based on a positive cytological finding in cerebrospinal fluid. The total lethality was 60.4%. The lethality was not significantly influenced by early diagnosis and treatment (within 48 hours), correct selection of antibiotic before knowing the cultivation finding and sensitivity. The total incidence of BM during the investigation period in the Faculty Hospital in Hradec Kralove was 0.51/1000, in mature neonates 0.36/1000 and 1.8/1000 in neonates with a low birth weight. PMID- 8348659 TI - [The importance of clinical symptoms in the diagnosis of bacterial meningitis in neonates]. AB - In a group of 32 neonates with bacterial meningitis (BM) the authors investigated the frequency of clinical symptoms and compared it with the frequency in a control group of 27 neonates where BM was ruled out. The following were significantly more frequent in neonates with BM: elevated temperature (p < 0.01) and seizures (p < 0.05). In the control group impaired muscular tonus was significantly more frequent (p < 0.05). Temperature had the highest diagnostic sensitivity (93.7%), followed by seizures (62.5%); exanthema had the highest specificity (92.6%), followed by bulging (92%). Neither sensitivity nor specificity of any of the investigated clinical symptoms reached the required level of 96%. PMID- 8348660 TI - [Chronic recurrent parotitis in children--diagnosis and therapy]. AB - The author presents a report on a group of 11 children with chronic recurrent parotitis, treated at the ENT department in Cadca. The author emphasizes the importance of sialography for establishment of the diagnosis of this disease and draws attention to therapeutic possibilities. PMID- 8348661 TI - [The present health and nutritional status of the pediatric population in the area of Orava]. AB - 410 children aged 11-14 years and 311 adolescents aged 15-18 years were examined in the region Orava. This region was selected for the survey because of high unemployment rates. The survey was focused on changes in nutritional indices in children and adolescents, as a consequence of changed food consumption patterns, caused by increased food prices and global socio-economic regression. Biochemical markers showed negative trends in serum lipid levels, especially a high prevalence of hypercholesterolaemia as well as that of vitamin C hyposaturation. This finding is related to impaired structure of consumed food, intake of food items of lower nutritional value, low intakes of fruit and vegetables, as shown by the analysis of dietary data. PMID- 8348662 TI - [Severe Amanita phalloides poisoning in a 7-year-old girl]. AB - Authors describe a case of a very severe poisoning, the prothrombin-time was less than 10% of the normal value and the child developed hepatic coma. We suppose, the favourable outcome may have been influenced by the treatment with Silymarin in combination with high doses of G-Penicillin. PMID- 8348663 TI - [Disorders of thermoregulation in children and their therapy]. PMID- 8348664 TI - [Pulmonary surfactant factor--composition and metabolism. 1]. PMID- 8348666 TI - [Changes in perinatal mortality in twins]. AB - Perinatal mortality of twins born in South Moravian Region in the years 1983-1987 was compared with that observed in the years 1970-1976. The perinatal mortality of twins decreased from 119,35 per thousand to 64,21 per thousand (the corresponding numbers for the whole population of the region in question are 16.48 per thousand and 11.30 per thousand respectively). The mortality of twins shows no reasonable changes. The early neonatal mortality decreased from 98.32 per thousand to 41.23 per thousand (the corresponding numbers in the whole population are 10.25 per thousand and 6.05 per thousand respectively). As in other countries the most important cause is the decrease of prematurity. This was observed both in the evaluation according to the birth weight and according to the gestational age as well as when the main cause of death was evaluated. Nevertheless also in the second sample a higher mortality of twins B than that of twins A was observed. The results of the leading clinics in the perinatal care show no more higher mortality of twins B namely due to the decrease of the number of RDS deaths. To achieve such object will be the nearest task in our perinatal care for the twins pregnancies and neonates. PMID- 8348665 TI - [Regulation of the synthesis and secretion of pulmonary surfactant. 2]. PMID- 8348667 TI - [The intensive care unit in the pediatric department of a district hospital. Problems and experience]. PMID- 8348668 TI - [Air pollution and the occurrence of recurrent respiratory tract diseases in children in the first years of life. II]. AB - In 200 3-7-year-old children in two localities of Bratislava-city with different concentrations of NO2, SO2, dustiness with different bioclimatic factors and a different epidemiological position the authors investigated their effect on the frequency, incidence and types of relapsing respiratory diseases during different months in 1991. The different concentrations of the above substances in the atmosphere of the two localities did not affect the number of respiratory diseases nor their annual or monthly incidence. In the place with the increased NO2 concentration a significantly higher number of serious forms of respiratory diseases was found in the investigated group. In the locality with a more favourable oecological and epidemiological situation the adverse effect of monthly NO2 concentrations was manifested when it was potentiated by the SO2 concentration and combined with dustiness and dust fall-out. The authors found a significant correlation between the incidence of relapsing respiratory diseases and the atmospheric temperature and its relative humidity in the course of different months of the year. PMID- 8348669 TI - [The sick building syndrome]. PMID- 8348670 TI - [Problems of immunization in Europe]. PMID- 8348671 TI - [The computer in the pediatric department]. PMID- 8348672 TI - Quasi-elastic light scattering determination of the size distribution of extruded vesicles. AB - The size distribution of phospholipid vesicles prepared by the freeze thaw extrusion method were determined by the non-perturbing technique of quasi-elastic light scattering (QELS) and compared to latex particles of known size. Multiangle QELS experiments were performed to avoid errors due to the angular dependence of the scattering function of the particles. The experimentally determined autocorrelation function was analyzed by multiple mathematical procedures, i.e. single exponential, CUMULANT, exponential sampling, non-negatively constrained least square and CONTIN, in order to select suitable models for vesicle characterization. The most consistent results were obtained with CUMULANT, non negatively constrained least square and CONTIN. In many instances single exponential analysis gave comparable results to these procedures, which indicates the vesicles have a narrow distribution of sizes. The influence of filter pore size, extrusion pressure and lipid concentration on the size and size distribution of extruded vesicles was determined. Extrusion through 100-, 200- and 400-nm pore size filters produced a unimodal distribution of vesicles, with somewhat smaller diameters as the extrusion pressure increased. The larger the filter pore size, the more dependent the vesicle size was on applied pressure. The observed vesicle size was independent of the lipid concentration between 0.1 and 10 mg ml-1. PMID- 8348673 TI - Effect of unilamellar vesicle size on ethanol-induced interdigitation in dipalmitoylphosphatidylcholine. AB - Unilamellar liposomes are widely used as model membranes to represent and study the properties of biological membranes and as potential drug delivery systems. It is well established that ethanol and other amphiphiles induce the interdigitated L beta I phase in multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). However, all of the work on this phase has been performed using the hand shaken multilamellar preparations. In the present report, we have studied the induction of interdigitation in a series of unilamellar vesicles prepared by sonication and by extrusion. The methods used to characterize the vesicles were freeze fracture electron microscopy and quasielastic light scattering (QELS). Two fluorescence methods were used to detect interdigitation, the DPH fluorescence quenching method (Nambi, P., Rowe, E.S. and McIntosh, T.J. (1988) Biochemistry 27, 9175-9182) and the pyrene-PC fluorescence method (Komatsu, H. and Rowe, E.S. (1991) Biochemistry 30: 2463-2470). It was found that sonicated vesicles are not stable in the presence of interdigitating concentrations of ethanol; they form higher aggregates at all temperatures examined. The behavior of the extruded vesicles was different from that of the SUV; each size studied was stable in the presence of ethanol, although they exhibited an increase in size. It was shown that extruded vesicles having a 200-nm or greater diameter become interdigitated in the presence of ethanol. The threshold concentration for interdigitation in vesicles is greater than that for MLVs and it decreases with increasing vesicle size, approaching the MLV value for the largest vesicles. PMID- 8348674 TI - Dithionite penetration through phospholipid bilayers as a measure of defects in lipid molecular packing. AB - The permeability of dithionite through bilayers was utilized to probe the structural defects in the bilayers of these lipids through their respective gel fluid and bilayer-hexagonal phase transitions. The water soluble dithionite ion penetrates intact bilayers very slowly. The rate of irreversible quenching of the fluorescence of NBD-PE labelled liposomes may thus be used as an indicator of the permeability of this ion through bilayers. The quenching rate has a fast and a slow component, the fast one corresponds to the quenching of fluorophores immediately accessible to the quencher, i.e. those on the outer surface of liposomes. The slower component represents the average rate of penetration of the quencher through the bilayer, to quench those fluorophores at the inner shells of the multilamellar vesicles. Both rates may be approximated by a single exponential function. The slow exponent is simply related to the permeability. The permeability of DMPC as a function of temperature shows a peak at the gel fluid phase transition at 24 degrees C, but returns to about the pre-transition value at temperatures above the phase transition. The permeability of egg PE shows a hump at 45 degrees C before the hexagonal phase transition at 65 degrees C is reached and becomes infinite at the hexagonal phase transition as all fluorophores are immediately accessible to the quencher. We believe that the permeability measured by this method relates more to the molecular packing defects which maximizes at the gel-fluid phase transition temperatures just below the bilayer-hexagonal phase transition, rather than the general packing order which simply changes with structural phases. PMID- 8348675 TI - Phase separated anionic domains in ternary mixed lipid monolayers at the air water interface. AB - A series of ternary mixed monolayers containing varying amounts of 1,2 dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and equimolar additions of 1 palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (LYSO-PC) and palmitic acid (PA) were studied at the air-water interface. These mixed monolayers were used to model phospholipid biomembrane interfaces resulting from phospholipase A2 (PLA2) hydrolysis. Recent work [D.W. Grainger A. Reichert, H. Ringsdorf and C. Salesse (1989) Biochim. Biophys. Acta. 1023, 365-379] has shown that PLA2 hydrolysis of pure phospholipid monolayers results in formation of large PLA2 domains at the air-water interface. These domains are proposed to result from PLA2 adsorption to phase separated regions in the hydrolyzed monolayer. To elucidate the phase behaviour in these monolayer systems, surface pressure-area isotherms were measured for the ternary mixtures on pure water and buffered subphases. Fluorescence microscopy at the air-water interface was used to image fluorescent probe-doped monolayer mixtures during isothermal compressions. A water-soluble cationic carbocyanine dye was used to probe the interfacial properties of the mixed monolayers. Isotherm data do not provide unambiguous evidence for either phase separation or ideal mixing of monolayer components. Fluorescence microscopy is more revealing, showing that lateral phase separation of microstructures containing palmitic acid occurred only when monolayer subphases contained Ca2+ ions at alkaline pH. At either low pH or on Ca(2+)-free subphases, phase separation was not observed. PMID- 8348676 TI - Spectroscopical characteristics of galactosylceramide-pyrene and ceramide-pyrene incorporated in model and in clathrin coated vesicles. AB - In order to control the ability of two pyrene-sphingolipids (ceramide-pyrene (Cpyr) and galactosylceramide-pyrene (GCpyr)) to monitor the changes in the lipid bilayer dynamics of cellular membranes, their incorporation in three populations of clathrin coated vesicles which differ in their structural characteristics (Bomsel et al. (1988) Biochemistry 27, 6808-6812) was studied by both absorbance and fluorescence spectroscopy. The method of injection of an ethanolic solution of probe was used. The analysis of the spectra recorded after injection into a free-membrane buffer allowed to discriminate two dispersion states (micellar or aggregated) of the probes. The micellar state was identified as the one suitable for the incorporation within the bilayer. Rising the temperature up to 18 degrees C for a membrane labeling with GCpyr and to 37 degrees C for a membrane labeling with Cpyr was found to be necessary because it allowed to slow down the aggregation process which inhibited the incorporation within the lipid bilayer. The excimer/monomer (E/M) fluorescence intensities ratio of GCpyr was found to be characteristic of each population of coated vesicles. Cpyr could not be used as a diffusion probe because it partly aggregated during the cooling step necessary to establish the E/M versus temperature plot in the heating mode. An important point which arises from these data is that the use of absorbance spectroscopy can avoid misinterpretation of the pyrene derivatives fluorescence spectra in terms of diffusion. PMID- 8348677 TI - Improved synthesis of (5Z)-7-(3-endo-[(benzenesulfonamido) bicyclo[2.2.1]heptyl]hept-5-enoic acid (S-145) derivatives and their iodine-125 labeled radioligands for the study of thromboxane A2 receptor. AB - An improved synthetic scheme for (5Z)-7-(3-endo-[(benzenesulfonamido) bicyclo[2.2.1]heptyl)-h ept-5-enoic acid (S145) and its analogs has been designed. The procedure involves direct sulfonylation of 2-allyl-3 aminobicyclo[2.2.1]heptane intermediate followed by ozonolysis and addition of a C5 carboxyl unit. The yield of the final product was significantly improved. (5Z) 7-(3-endo-[(4-iodobenzenesulfonamido)-bicyclo [2.2.1]heptyl)hept-5-enoic acid (HS 145) and (5Z)-7-(3-endo-[(4-hydroxy-benzensulfonamido)-bicyclo [2.2.1]heptyl)hept 5-enoic acid (HS-145) were synthesized directly without any protection and deprotection steps. [125I](5Z)-7-(3-endo-[(4- iodobenzensulfonamido) bicyclo[2.2.1]heptyl)hept-5-enoic acid ([125I]HS-145) was prepared from IS-145 through an organotin intermediate and [125I]sodium iodide with high specific radioactivity and good recovery of radioactivity. [125I](5Z)-7-(3-endo-[(4 hydroxy 3-iodo-benzenesulfonamido)-bicyclo[2.2.1]-heptyl)hept-5-enoic acid ([125I]HS-145) was prepared by direct iodination with sodium iodide using a modified chloramine-T method. Both [125I]HS-145 and [125I]HS-145 were found to be valuable radioligands for studying thromboxane A2 (TXA2) receptor. PMID- 8348678 TI - Density fluctuations and rotational isomerization in phospholipid bilayers as studied by ultrasonic absorption spectroscopy. AB - Broadband ultrasonic absorption spectra are discussed for some aqueous solutions of single-walled phospholipid bilayer vesicles. It is shown that the excess absorption found with all samples can be represented by a sum of a Debye-type relaxation term with discrete relaxation time and a Fixman-Kawasaki term. The former term reflects the kinetics of structural isomerization of the hydrocarbon chains. The values of its relaxation time (0.09-0.56 ns) agree with those for pure n-alkanes of comparable length. The latter terms seems to be due to density fluctuations in the hydrocarbon part of the double layer. Fluctuation correlation lengths between 1 and 30 A result from the analysis of the ultrasonic spectra. PMID- 8348680 TI - Oxygen extraction is altered by endotoxin during tamponade-induced stagnant hypoxia in the dog. AB - The present study used a model of cardiac tamponade to investigate the effects of endotoxin on the oxygen extraction capabilities of the body during an acute reduction in blood flow, when blood volume and arterial oxygen content were maintained. In 21 pentobarbital anesthetized, mechanically ventilated dogs, two catheters were introduced into the pericardial space to induce cardiac tamponade, and simultaneously to measure the intrapericardial pressure. Oxygen uptake (VO2) was determined from the expired gases. Oxygen delivery (DO2) was calculated by the product of the thermodilution cardiac index and the arterial oxygen content. Eleven dogs received 2 mg/kg Escherichia coli endotoxin, followed by generous saline infusion (20 ml/kg.hr). Ten dogs served as a control group. In each dog, DO2 was progressively reduced by pericardial saline infusion at a rate of 40 ml/hr for the first hour and 30 ml/hr thereafter. Critical O2 delivery (DO2crit) and critical O2 extraction ratio (O2ERcrit) were determined from a plot of VO2/DO2 for each individual dog. The DO2crit was greater in the endotoxic than in the control group (12.1 +/- 3.1 ml/kg.min vs. 9.6 +/- 1.6 ml/kg.min; P < 0.05). Endotoxin at the dose used did not alter VO2 (or critical VO2). Accordingly, O2ERcrit was significantly lower in the endotoxic than in the control animals (47.2% +/- 5.7% vs. 60.3% +/- 10.6%; P < 0.01). The mixed venous PO2 levels at DO2crit were higher in the endotoxic than in the control group (30.6 +/- 6.1 mm Hg vs. 25.4 +/- 5.2 mm Hg; P < 0.05). Arterial blood lactate concentration was higher in the endotoxic than in the control dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348679 TI - Systemic hemodynamic and microvascular responses in spontaneously hypertensive rats during Escherichia coli bacteremia. AB - Renovascular hypertension profoundly alters skeletal muscle arteriolar responses to sepsis, yet systemic hemodynamics to sepsis are not affected by hypertension. In this study, we hypothesized that microvascular responses of skeletal muscle and systemic hemodynamics are changed during high- and low-cardiac-output Escherichia coli bacteremia in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). During high-cardiac-output bacteremia, blood pressure and heart rate increased in WKY, but blood pressure decreased in SHR. During low cardiac-output bacteremia, blood pressure initially decreased in WKY, while in SHR, pressure dropped significantly and remained severely depressed. Heart rate increased by 50% in SHR, but only by 10-15% in WKY during low-cardiac-output bacteremia. Large A1 and A2 arterioles constricted in both WKY and SHR during both phases of bacteremia. Small A3 and A4 arterioles dilated in WKY during bacteremia, but this small arteriole dilation was blunted in SHR. However, nitroprusside, an endothelium-derived relaxing factor (EDRF)-independently acting vasodilator, caused maximal dilation of these small arterioles of SHR. We conclude that there are profound changes and differences in systemic hemodynamics during bacteremia between the normotensive and the genetically hypertensive groups, whereas despite a possibly decreased endothelium-dependent vasodilator responsiveness in small arterioles of SHR during bacteremia, overall blood flow changes in skeletal muscle were similar among the two groups. PMID- 8348681 TI - Comparison of gastric luminal and gastric wall PCO2 during hemorrhagic shock. AB - Measurement of gastric wall PCO2 has emerged as a promising monitor of perfusion deficits during low-flow states of circulatory shock. In the present study, gastric luminal PCO2 measured with the gastric tonometer was compared with the PCO2, measured directly in the wall of the stomach during hemorrhagic shock in two groups of five Sprague-Dawley rats. One group was pretreated with the H2 blocker, ranitidine. During a 120-min interval of hemorrhage, tonometer PCO2 increased from 60 +/- 7 mmHg to 90 +/- 10 mmHg, and time-coincident gastric wall PCO2 from 52 +/- 5 mmHg to 131 +/- 14 mmHg. Following reinfusion of shed blood, tonometer PCO2 remained elevated for an interval exceeding 60 min, but gastric wall PCO2 returned to control levels within approximately 10 min. Ranitidine pretreatment did not alter the relationships between gastric wall PCO2 and tonometer PCO2. These observations indicate that gastric luminal PCO2 underestimates relatively rapid increases in gastric wall PCO2 during profound hemorrhagic shock in rats. PMID- 8348682 TI - (+)Naloxone potentiates the inotropic effect of epinephrine in the isolated dog heart. AB - Naloxone potentiates the inotropic effect of circulating catecholamines in the isolated canine heart. The stereospecificity of this response was evaluated with the aid of the less active (+)enantiomer of naloxone. The more common (-)isomer of naloxone increased the contractile response to epinephrine only at the higher dose tested (4 mg). This effect of naloxone was not observed at a tenfold lower dose (0.4 mg), indicating a very narrow dose-response range. (+)Naloxone was effective at the lower dose and was, therefore, equal to or better than ( )naloxone in potentiating the inotropic effect of epinephrine. When introduced afterward, (-)naloxone did not add to the effect of (+)naloxone. These data suggest that naloxone modifies cellular responsiveness to catecholamines through a nontraditional opiate receptor, through a nonopiate receptor, or through a nonreceptor mechanism. PMID- 8348683 TI - Reevaluation of the linkage between acute hemorrhagic shock and bacterial translocation in the rat. AB - The present study was undertaken to determine the conditions under which acute periods of hemorrhagic shock induce bacterial translocation. Rats (at least six per group) were anesthetized intraperitoneally with the barbiturate, pentobarbital (50 or 65 mg/kg), or the inhalation anesthetic methoxyflurane. Following anesthesia, the femoral artery was catheterized, from which blood was withdrawn to maintain a mean arterial blood pressure of 30 mmHg for 30, 60, or 90 min, followed by reinfusion of shed blood. Instrumented, but nonshocked animals served as controls. Rats were sacrificed at 0, 2, or 24 hr postshock, and quantitative bacterial cultures of the mesenteric lymph node complex (MLN), liver, and spleen were made. Within groups, the effects of heparinization were also determined. In pentobarbital-treated animals, regardless of the extent of heparinization, consistent translocation to both MLN and distant organs occurred when shock was prolonged for 90 min, and assessment of translocation was made 24 hr after reinfusion of shed blood. Furthermore, a mortality rate of approximately 30% was found in rats subjected to this protocol. The magnitude of translocation was less consistent, and did not differ from that in sham shock controls, under other conditions of shock and evaluation. In rats anesthetized with methoxyflurane, no mortality occurred, and no statistical significance between the incidence or degree of translocation in shocked animals vs. sham shock controls could be demonstrated, regardless of the shock protocol. In additional studies, effects of these anesthetics on intestinal morphology and superior mesenteric arterial (SMA) flow in the context of hemorrhagic shock were assessed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348684 TI - Extracorporeal circulation: in vivo and in vitro analysis of complement activation by heparin-bonded surfaces. AB - Complement activation was analyzed during extracorporeal CO2 removal to compare heparin-coated with standard surfaces where systemic heparinization was required. In vivo studies were performed in adult sheep for up to 5 days under standardized conditions using a capillary membrane oxygenator. Applying assays for hemolytic complement function (CH50, APH50) and C3-derived split products, we found that complement activation was markedly reduced in sheep connected to an extracorporeal circuit where heparin was covalently bound by end-point attachment. In addition, incubation of human serum in a miniaturized circulation system revealed less complement activation by heparin-bonded surfaces, as evaluated by enzyme-linked immunosorbent assays for C3a and the activation specific protein-protein complexes, C1rsC1 inhibitor (classical pathway) and C3b(Bb)P (alternative pathway). Our results provide further evidence that biocompatibility can be improved by end-point attachment of heparin to the surfaces of the extracorporeal circuit. PMID- 8348685 TI - Comparison of effects of dopamine hydrochloride and dopexamine hydrochloride on abdominal and femoral hemodynamics in anesthetized dogs. AB - The effects of dopamine and dopexamine administered in graded intravenous bolus injections (0.1-51.2 micrograms.kg-1) were compared in the renal and femoral, and in a number of splanchnic vessels at the organ level simultaneously in anesthetized dogs. Hemodynamic data are presented for each artery as conductance, which was obtained by dividing mean flow by mean arterial pressure. The data were analyzed in two different ways: 1) by responses at intervals of 3 sec to 12.8 micrograms dopamine or dopexamine during 1 min, and 2) by dose-response curves. Additionally, urine volume was measured during dopamine and dopexamine administration. During a period of 1 min after an injection of dopamine, early and late effects could be distinguished, while heart rate was unaltered. In the superior mesenteric, inferior mesenteric, splenic, common hepatic, renal, and femoral arteries, an early (at 18-21 sec) reduction in conductance was seen. The early reduction was often followed by an increase above the preinjection level. After dopexamine, the early reduction in conductance was not seen, except in the left gastric artery. In contrast to the effect of dopamine, dopexamine induced a more pronounced increase during the late phase. Contrary to dopamine, dopexamine increased the conductance in the common hepatic artery bed. It remains questionable whether dopaminergic receptors are present in this vascular bed. Dopamine raised blood pressure and urine production dose-dependently. Dopexamine decreased aortic pressure. Low dosages of dopexamine increased urine production, without raising renal blood flow. An advantage of dopexamine over dopamine could be that dopexamine does not stimulate alpha-adrenergic receptors. PMID- 8348686 TI - Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. AB - Increasing evidence suggests that angiotensin II (Ang II) may act as a growth factor for the heart. However, direct effects of Ang II on mammalian cardiac cells (myocytes and nonmyocytes), independent of secondary hemodynamic and neurohumoral effects, have not been well characterized. Therefore, we analyzed the molecular phenotype of cultured cardiac cells from neonatal rats in response to Ang II. In addition, we examined the effects of selective Ang II receptor subtype antagonists in mediating the biological effects of Ang II. In myocyte culture, Ang II caused an increase in protein synthesis without changing the rate of DNA synthesis. In contrast, Ang II induced increases in protein synthesis, DNA synthesis, and cell number in nonmyocyte cultures (mostly cardiac fibroblasts). The Ang II-induced hypertrophic response of myocytes and mitogenic response of fibroblasts were mediated primarily by the AT1 receptor. Ang II caused a rapid induction of many immediate-early genes (c-fos, c-jun, jun B, Egr-1, and c-myc) in myocyte and nonmyocyte cultures. Ang II induced "late" markers for cardiac hypertrophy, skeletal alpha-actin and atrial natriuretic factor expression, within 6 hours in myocytes. Ang II also caused upregulation of the angiotensinogen gene and transforming growth factor-beta 1 gene within 6 hours. Induction of immediate-early genes, late genes, and growth factor genes by Ang II was fully blocked by an AT1 receptor antagonist but not by an AT2 receptor antagonist. These results indicate that: (1) Ang II causes hypertrophy of cardiac myocytes and mitogenesis of cardiac fibroblasts, (2) the phenotypic changes of cardiac cells in response to Ang II in vitro closely mimic those of growth factor response in vitro and of load-induced hypertrophy in vivo, (3) all biological effects of Ang II examined here are mediated primarily by the AT1 receptor subtype, and (4) Ang II may initiate a positive-feedback regulation of cardiac hypertrophic response by inducing the angiotensinogen gene and transforming growth factor-beta 1 gene. PMID- 8348687 TI - Signal transduction pathways of angiotensin II--induced c-fos gene expression in cardiac myocytes in vitro. Roles of phospholipid-derived second messengers. AB - Angiotensin II (Ang II) causes a rapid induction of immediate-early genes and hypertrophy in the cardiac myocyte. However, the signaling mechanism of Ang II induced immediate-early gene expression in cardiac myocytes has not been characterized. Therefore, we examined signal transduction of Ang II in neonatal rat cardiac myocytes, using c-fos gene expression as a model system. Transient transfection of c-fos reporter gene constructs indicated that the serum response element is not only required but also sufficient for Ang II-induced activation of the c-fos promoter. Ang II is known to cause an increase in [Ca2+]i. We found that Ang II also causes a small increase in cAMP in cardiac myocytes. However, the Ca2+/cAMP response element of the c-fos gene was not sufficient to confer Ang II responsiveness to the c-fos promoter, and inhibitors of protein kinase A had no effects on Ang II-induced c-fos expression. On the other hand, chelating intracellular Ca2+ with BAPTA-AM inhibited Ang II-induced c-fos expression in a dose-dependent manner, suggesting that Ca2+ is required for Ang II-induced signaling. Measurements of phospholipid-derived second messengers revealed that Ang II increased production of inositol trisphosphate, diacylglycerol, phosphatidic acid, and arachidonic acids, resulting in a sustained increase in protein kinase C activity. This and other evidence suggest that Ang II activates phospholipase C, phospholipase D, and possibly phospholipase A2. All of these second-messenger systems are activated through the AT1 receptor. Pharmacological inhibition of phospholipase C or downregulation of protein kinase C significantly suppressed Ang II-induced c-fos expression. In conclusion, Ang II activates multiple phospholipid-derived second-messenger systems via the AT1 receptor in cardiac myocytes. Among these second-messenger systems, phospholipase C and protein kinase C seem essential for Ang II-induced c-fos gene expression, whereas Ca2+ may play a permissive role. Finally, the "Ang II response element" of the c fos gene maps to the protein kinase C-dependent portion of the serum response element. PMID- 8348688 TI - Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. AB - Two subtypes of angiotensin II (Ang II) receptors (AT1 and AT2) are distinguished by using the respective specific antagonists. In the present study, we report the regulation of cardiac AT1 type A (AT1A) receptor mRNA levels and the expression pattern of AT1 and AT2 receptors in the growth of the heart and the development and regression of cardiac hypertrophy. The ventricular AT1A mRNA level and the density of Ang II receptors at the neonatal period were significantly increased (3.5-fold and 2.5-fold, respectively) and then downregulated with maturation. The cardiac hypertrophy established in spontaneously hypertensive rats or two-kidney one-clip renovascular hypertensive rats resulted in substantial increases in ventricular AT1A mRNA levels (threefold) and Ang II receptor densities (twofold) as compared with those in respective control rats, whereas the receptor affinity was similar. The proportion of AT1 and AT2 subtypes in the specific Ang II binding in ventricular membranes prepared from normal adult rats was nearly equal. This proportion did not change significantly in the development of myocardial hypertrophy. The regression of cardiac hypertrophy by the normalization of elevated blood pressure completely reversed the increased levels of AT1A mRNA and the receptor density to the control level. Thus, AT1 and AT2 receptors are present in rat ventricular myocardium, and their expression is developmentally regulated and upregulated in response to hypertrophic change. Ang II action exerted through the increased number of Ang II receptors may contribute to the growth of the heart and thus to the maintenance of established hypertrophy as one of the hormones involved in hypertrophy development. PMID- 8348689 TI - Effects of adenosine and its analogues on isolated intracerebral arterioles. Extraluminal and intraluminal application. AB - We evaluated the responses of brain parenchymal arterioles to intraluminal and extraluminal application of adenosine and its analogues. Intracerebral arterioles (28.4- to 60.3-microns diameter) were isolated from Sprague-Dawley rats, cannulated with micropipettes, and perfused in vitro. Both extraluminal and intraluminal adenosine, 5'-(N-ethylcarboxamido)adenosine (NECA), R-N6 (phenylisopropyl)adenosine (R-PIA), and S-N6-(phenylisopropyl)adenosine (S-PIA) elicited concentration-dependent dilation of these arterioles, but intraluminal application was less potent and efficacious than extraluminal application. Inosine was not vasoactive. A common order of agonist potency (NECA > adenosine > R-PIA > or = S-PIA) was determined for both extraluminal and intraluminal application. Theophylline (10 microM) caused a rightward shift of the adenosine concentration-response curve and a 50-fold reduction in potency. Intraluminal theophylline was one sixth as effective as extraluminal theophylline in antagonizing the extraluminal adenosine response, whereas intraluminal 8 sulfophenyltheophylline, a polar theophylline derivative, was ineffective. Polyadenylic acid (PolyA, 1 microM), an adenosine polymer that does not penetrate the endothelium, induced a dilation of 44.2 +/- 5.3% when applied extraluminally but had no effect when infused intraluminally. The dilator effect of PolyA was antagonized by theophylline. We conclude that: (1) intraluminal adenosine and its analogues are effective dilators of intracerebral arterioles, (2) the dilator effects of both intraluminally and extraluminally applied adenosine are predominantly mediated by A2-type receptors, and (3) adenosine receptors mediating vasodilation are not present on the luminal surface of the endothelium. PMID- 8348690 TI - Myocardial oxygenation in dogs during partial and complete coronary artery occlusion. AB - Regional myocardial oxygenation was assessed during partial and complete coronary artery occlusion using near infrared spectroscopy. In eight open-chest dogs, partial occlusions resulting in an approximately 42% decrease in left anterior descending coronary artery (LAD) blood flow produced an approximately 21% decrease in tissue O2 stores (tissue oxyhemoglobin plus oxymyoglobin) and no change in the oxidation level of mitochondrial cytochrome aa3. An approximately 81% reduction in LAD blood flow produced nadir levels of tissue oxyhemoglobin plus oxymyoglobin, maximal levels of deoxyhemoglobin plus deoxymyoglobin, a decline in tissue blood volume, and an approximately 39% decrease in cytochrome aa3 oxidation level. These changes were associated with an approximately 52% decrease from the preischemic baseline in mean transmural myocardial blood flow, measured by radiolabeled microspheres, and an approximately 41% decrease in myocardial O2 consumption. Complete occlusion resulted in further decreases in myocardial blood flow, O2 consumption, tissue blood volume, and cytochrome aa3 oxidation state but also produced increases in tissue O2 stores to above the nadir levels noted during partial occlusion. These results indicate that decreases in O2 delivery during partial coronary occlusion increase O2 extraction to sustain mitochondrial O2 availability, but as little as a 52% reduction in myocardial blood flow produces maximal O2 extraction and depletion of tissue O2 stores. Mitochondrial O2 availability is restricted further during complete occlusion because of limited O2 delivery and, possibly, decreases in tissue blood volume and O2 extraction. PMID- 8348691 TI - Modification of myogenic intrinsic tone and [Ca2+]i of rat isolated arterioles by ryanodine and cyclopiazonic acid. AB - The role of the sarcoplasmic reticulum (SR) in regulating myogenic tone and [Ca2+]i was examined with ryanodine and cyclopiazonic acid (CPA) in the rat skeletal muscle arteriole (A(sk)) and mesenteric arteriole (Ams). Arterioles were cannulated at both ends to control luminal pressure in a tissue bath. Luminal diameter was measured with a video-monitored microscopic system. Fura 2-AM was loaded to measure [Ca2+]i using the fluorescence intensity ratio at excitation wavelengths of 340 to 380 nm (F340/380). The myogenic response (luminal pressure was increased from 40 to 100 mm Hg) and the intrinsic tone at 40 mm Hg were observed in A(sk) but not in Ams. Ryanodine (10(-5) M decreased the steady-state diameter of A(sk) from 138 +/- 8 to 85 +/- 9 microns (P < .05) and increased the F340/380 ratio; these effects were reversed by nifedipine or Ca(2+)-free solution. Ryanodine shifted the [Ca2+]o-contraction response curve upward. CPA (10(-5) M) also decreased the steady-state diameter of A(sk) from 131 +/- 7 to 98 +/- 11 microns (P < .05). In contrast, Ams responded to neither ryanodine nor CPA. Caffeine-induced contractions were significantly reduced by either ryanodine or CPA in both arterioles. These results indicate that SR dysfunction increased the susceptibility of the arteriolar tone to [Ca2+]o and enhanced the tone of A(sk). In conclusion, the SR function may play a critical role in regulating [Ca2+]i and the intrinsic tone of A(sk) that was myogenically active at physiological luminal pressure. PMID- 8348692 TI - ATP-dependent closure and reactivation of inward rectifier K+ channels in endothelial cells. AB - This report presents the results of a patch-clamp study examining the role of intracellular ATP in the regulation of endothelial inward rectifier K+ channels. Administration of ATP to the cytosolic surface of inside-out patches reversibly activated the K+ channel within seconds. ATP (1 mM) increased the mean open probability by a factor of 3.5, primarily by increasing the number of openings. Administration of the nonhydrolyzable ATP analogue ATP-gamma-S failed to modulate channel activity. Inhibition of ATP synthesis by administration of cyanide plus iodoacetate resulted in channel closure within 1 to 6 minutes. In experiments in which ATP was coadministered with the metabolic blockers, the channel activity continued unchanged for up to 30 minutes, but when ATP was removed, the activity rapidly decayed. We propose that normal functioning of the inward rectifier K+ channel is ATP dependent. Phosphorylation of the channel molecule is probably essential for maintaining activity. PMID- 8348693 TI - Repeated dipyridamole administration enhances collateral-dependent flow and regional function during exercise. A role for adenosine. AB - Two main hypotheses concerning the mechanisms responsible for coronary collateral growth suggest the involvement of chemical or mechanical factors. Since we recently demonstrated that the development of the coronary collateral circulation is not closely related to the extent or duration of myocardial ischemia, we hypothesized that chronic repeated vasodilation and increased myocardial blood flow using dipyridamole would enhance collateral development in miniswine with an ameroid-occluded left circumflex coronary artery (LCx). Two days after surgical instrumentation, the animals received dipyridamole (n = 9), diltiazem as an adenosine-independent vasodilator (n = 8), or control vehicle (n = 7) 90 minutes per day, 5 days per week for 8 weeks. At 5 and 8 weeks, transmural blood flow and systolic wall thickening were measured during infusion of dipyridamole, diltiazem, or vehicle. Transmural blood flow increased similarly in the LCx and nonoccluded regions at 30 and 60 minutes during infusion of either vasodilator. Thus, we believe that similar mechanical stimulation resulted from dipyridamole and diltiazem infusion. There was no change in blood flow during administration of the vehicle. Systolic wall thickening in the collateral-dependent region was not altered by infusion of dipyridamole, diltiazem, or vehicle. Therefore, both vasodilators increased blood flow without eliciting ischemia. After 8 weeks of repeated treatment with each pharmacological agent, at least 24 hours after the last drug infusion, near maximal physiological capacity of the coronary collateral vessels was assessed during treadmill running (approximately 240 beats per minute). Transmural myocardial blood flow ratios, expressed as flow in the LCx divided by flow in the nonoccluded region of the left ventricle, were similar at rest for animals treated with dipyridamole (0.90 +/- 0.03), diltiazem (0.97 +/ 0.05), and control vehicle (0.89 +/- 0.02). However, collateral-dependent myocardial blood flow during exercise was greater (P < .05) in the dipyridamole treated animals (0.78 +/- 0.04) than in either diltiazem-treated (0.63 +/- 0.09) or vehicle-treated (0.62 +/- 0.02) animals. LCx systolic wall thickening at rest was similar in animals treated with dipyridamole (44.4 +/- 6.3%), diltiazem (42.2 +/- 3.0%), and control vehicle (38.1 +/- 2.8%). During exercise, however, myocardial function in the collateral-dependent region was greater (P < .05) in the dipyridamole-treated (39.2 +/- 5.2%) compared with diltiazem-treated (23.9 +/ 4.0%) and vehicle-treated (26.9 +/- 2.9%) animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8348695 TI - Attenuation of ecto-5'-nucleotidase activity and adenosine release in activated human polymorphonuclear leukocytes. AB - To examine whether activation of polymorphonuclear leukocytes attenuates release of adenosine through attenuation of their own ecto-5'-nucleotidase activity, human polymorphonuclear leukocytes were incubated with and without exposure to either N-formyl-methionyl-leucyl-phenylalanine (FMLP) or complement C5a. Ecto-5' nucleotidase activity of polymorphonuclear leukocytes was attenuated by both FMLP and complement C5a (22.7 +/- 3.6 vs 9.7 +/- 2.6 nmol/min per 10(7) cells at 10( 6) M FMLP, P < .05; 21.5 +/- 2.2 vs 10.2 +/- 1.2 nmol/min per 10(7) cells at 5 x 10(-7) g/mL complement C5a, P < .001), whereas cytosolic 5'-nucleotidase activity was not affected by either FMLP or complement C5a. These reductions of ecto-5' nucleotidase activity that were caused by both FMLP and complement C5a were dose and time dependent and were inhibited by superoxide dismutase. Desferrioxamine did not inhibit the decreases in ecto-5'-nucleotidase. In accordance with the decreases in ecto-5'-nucleotidase activity, release of adenosine was attenuated in the FMLP-pretreated and complement C5a-pretreated polymorphonuclear leukocytes, which were restored by concomitant administration of superoxide dismutase. The viability of FMLP-pretreated and complement C5a-pretreated polymorphonuclear leukocytes was markedly decreased compared with the untreated group after 60 minutes of hypoxia followed by 60 minutes of reoxygenation. Thus, we conclude that: (1) activation of polymorphonuclear leukocytes attenuates their own ecto-5'-nucleotidase activity and thereby reduces adenosine release, (2) reduction of ecto-5'-nucleotidase activity is attributable to generated superoxide anion in polymorphonuclear leukocytes, and (3) viability of polymorphonuclear leukocytes after hypoxia and reoxygenation largely depends on the extents of decreases in ecto-5'-nucleotidase activity. PMID- 8348694 TI - Loss of asymmetric distribution of sarcolemmal phosphatidylethanolamine during simulated ischemia in the isolated neonatal rat cardiomyocyte. AB - In the present study we have investigated the reorganization of the sarcolemmal phospholipids during the first 60 minutes of simulated ischemia ("ischemia") as induced by anoxia, volume restriction, and nutrient deprivation. Experiments were carried out on [3H]acetate-labeled neonatal rat cardiomyocytes and isolated (nonradiolabeled) sarcolemmal membranes obtained from the same culture system. After 60 minutes of "ischemia," cellular high-energy phosphate (ATP) levels had decreased to approximately 40% of the control values, but no significant phospholipid hydrolysis was detected. Labeling experiments using the nonpermeant (primary amine-containing phospholipid) probe trinitrobenzenesulfonic acid and nonlytic treatment with (different) exogenous phospholipases A2 were both indicative of a shifted transbilayer distribution of the hexagonalII phase preferring and fusion-promoting sarcolemmal phosphatidylethanolamine in favor of the outer membrane leaflet. This specific change in sarcolemmal phospholipid asymmetry preceded the loss of integrity of the sarcolemma, monitored by the release of lactate dehydrogenase as well as by scanning electron microscopy. It is proposed that, in addition to the previously reported lateral phospholipid reorganization, uncontrolled transbilayer movement of the non-bilayer-preferring phosphatidylethanolamine from the inner to the outer leaflet of the sarcolemma is an additional factor in destabilizing the lipid bilayer, eventually leading to the irreversible membrane damage seen after a prolonged period of ischemia. PMID- 8348696 TI - Effects of brief repetitive ischemia on contractility, relaxation, and coronary flow. Exaggerated postischemic diastolic dysfunction in pressure-overload hypertrophy. AB - The recovery of systolic and diastolic function during unstable angina may be modified by the repetition of brief episodes of ischemia and by the presence of left ventricular hypertrophy (LVH). We studied the effects of six consecutive 5 minute cycles of no-flow ischemia and reperfusion followed by 25 minutes of recovery in isovolumic red blood cell-perfused hearts from aortic-banded rats with chronic LVH (n = 8) and sham-operated control rats (n = 8). At baseline (left ventricular end-diastolic pressure [LVEDP], 10 mm Hg), left ventricular developed pressure (123 +/- 5 versus 114 +/- 5 mm Hg/g) and coronary flow [2.5 +/ 0.3 versus 2.2 +/- 0.2 (mL/min)/g] were similar in LVH versus control rats. Repetitive ischemia was associated with progressive depression of postischemic recovery of left ventricular systolic function, and the recovery of left ventricular developed pressure after the final 25-minute reperfusion period was similar in LVH versus control rats (61 +/- 6% versus 72 +/- 4% of baseline, P = NS). Although there was no increase in isovolumic LVEDP during the initial cycle of transient ischemia, both groups showed a rapid and similar rise in LVEDP during subsequent ischemic cycles (delta 82 +/- 8 versus delta 89 +/- 7 mm Hg/g in response to the final ischemia cycle for LVH versus control rats, respectively; P = NS). The control hearts showed complete restoration of LVEDP to baseline during final reperfusion, whereas the LVH hearts showed prolonged and severe postischemic diastolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348697 TI - Development of the cardiac coronary vascular endothelium, studied with antiendothelial antibodies, in chicken-quail chimeras. AB - The endothelium of the coronary vascular system has been described in the literature as originating from different sources, varying from aortic endothelium for the main coronary stems, endocardium for the intramyocardial network, and sinus venosus lining for the venous part of the coronary system. Using an antibody against quail endothelial cells (alpha-MB1), we investigated the development of the coronary vascular system in the quail (Hamburger and Hamilton stages 15 to 35) and in a series of 36 quail-chicken chimeras. In the chimeras, pieces of quail epicardial primordium and/or liver tissue were transplanted into the pericardial cavity of a chicken host. The results showed that the coronary vascular endothelial distribution closely followed the formation of the epicardial covering of the heart. However, pure epicardial primordium transplants did not lead to endothelial cell formation, whereas a liver graft with or without an epicardial contribution did have this capacity. The first endothelial cells were seen to reach the heart at the sinus venosus region, subsequently spreading through the inner curvature to the atrioventricular sulcus and the outflow tract and, last of all, over the ventricular surfaces. At these sites, the precursor cells and small vessels were seen to invade the sinus venosus wall, the ventricular and atrial myocardium, and the mesenchymal border of the aortic orifice. Connections with the endocardium of the heart tube were only observed in the right ventricular outflow region. Initially, the connections with the aortic endothelium were multiple, but later in development only two of these connections persisted to form the proximal part of the two main coronary arteries. Connections to the pulmonary orifice were never observed. Our transplantation data showed that the entire coronary endothelial vasculature originated from an extracardiac source. Moreover, using the developing subepicardial layer as a matrix, we showed that the endothelial cells reached the heart from the liver region. Ingrowth into the various cardiac segments was also observed. Implications for the relation to specific congenital cardiac malformations are discussed. PMID- 8348698 TI - Expression of basic fibroblast growth factor and its receptor by smooth muscle cells and endothelium in injured rat arteries. An en face study. AB - Release of endogenous basic fibroblast growth factor (bFGF) has been shown to initiate smooth muscle cell (SMC) proliferation following balloon catheter denudation in rat arteries. The mechanisms that contribute to the continued replication of the cells that subsequently form the neointima are not well understood. We have examined expression of bFGF and fibroblast growth factor receptor 1 (FGFR-1) in luminal SMCs as well as endothelium at various times after injury, which allowed us to study both replicating as well as quiescent cells. Using in situ hybridization on en face preparations, we were able to detect mRNA in luminal cells that was not observed by analysis of artery cross sections. We demonstrate that mRNA for bFGF was found in replicating SMCs and endothelial cells. bFGF mRNA was not detectable in either cell type at quiescence despite nuclear staining for bFGF. Expression of FGFR-1 mRNA was observed in replicating endothelial and SMCs at similar times after injury. These data provide evidence that in injured arteries the ligand/receptor system of bFGF and FGFR-1 may be involved in the continued proliferative response of SMCs leading to neointima formation. Furthermore, our results suggest a role for bFGF in reestablishing the endothelial lining in denuded vessels. PMID- 8348699 TI - The impact of obesity on hyperandrogenism and polycystic ovary syndrome in premenopausal women. PMID- 8348700 TI - Interindividual differences in the pituitary-thyroid axis influence the interpretation of thyroid function tests. AB - OBJECTIVE: We investigated interindividual differences in the shape, slope and setpoint of the pituitary-thyroid axis (PTA) in normal persons. Based on these physiological data we propose a novel bivariate concept for the interpretation of thyroid function tests which is less biased by interindividual differences in the PTA than the currently used univariate approach. DESIGN: In two separate trials (A and B), healthy volunteers were given small, increasing doses of T3 (7.5-45 micrograms/day orally) over 5 days. The regulation characteristics of the individual PTAs and the effects of age and gender were assessed by general linear regression models. In addition, serum samples were collected from normal persons to establish the proposed bivariate approach for the interpretation of thyroid function tests. SUBJECTS: The regulatory characteristics of the PTA were determined in a total of 21 normal volunteers (eight females, 13 males; age 24-49 years). Single blood samples were collected from 257 normal volunteers. The participants had no history of pituitary or thyroid disease. MEASUREMENTS: Free and total thyroid hormone and TSH concentrations were determined in the serum. All samples from one person were analysed in the same assay in duplicate. RESULTS: A log-linear relationship between T3 and TSH was found to describe best the individual PTA (multiple r = 0.96). However, significant differences in the setpoint (P < 0.001) and to a lesser degree in the slope (P < or = 0.05) of the PTA were detected; this variability was not dependent on age or gender. Since these findings invalidate the assumptions on which the current univariate interpretation of thyroid function tests is based, we propose a novel model for the evaluation of thyroid function tests derived from the experimentally determined shape and average slope of the PTA. CONCLUSIONS: The presence of significant age and gender-independent interindividual variations in the setpoint of the pituitary-thyroid axis raises conceptual problems with the current approach for interpreting thyroid function tests. An easy to use graphical bivariate representation of the normal ranges for thyroid function tests is presented and exemplified by the thyroid hormone and TSH measurements in a large reference population. This concept should improve the diagnostic accuracy in the borderline-normal, and particularly subclinical hypothyroid region of these hormone measurements. PMID- 8348701 TI - Serious, prolonged hypoglycaemia with glibenclamide in a patient with Mendenhall's syndrome. AB - Mendenhall's syndrome, characterized by familial insulin resistant diabetes, pineal hyperplasia and multiple somatic abnormalities, is associated with defects involving the alpha-subunit of the insulin receptor. The associated insulin resistant diabetes is extremely difficult to treat; insulin is required in very large doses to control hyperglycaemia and oral hypoglycaemic agents are ineffective. We report a case of severe, prolonged hypoglycaemia that occurred in a 24-year-old patient with Mendenhall's syndrome following therapy with glibenclamide. He had glibenclamide 10 mg daily for 1 week following which he was admitted to hospital in hypoglycaemic coma with blood glucose levels < 1.0 mmol/l. This subject had undergone hypophysectomy at the age of 11 years. Prior to pituitary ablation, oral hypoglycaemic agents did not improve glycaemic control. Thus, previous hypophysectomy in this patient appears to have made it possible for glibenclamide to exert its hypoglycaemic effect. The occurrence of hypoglycaemia in this patient suggests alternative mechanisms for insulin action in conditions characterized by severe insulin resistance due to insulin receptor defects. PMID- 8348702 TI - Propranolol, diltiazem and cardiac and thyroid functions in hyperthyroidism. PMID- 8348703 TI - Glucokinase and non-insulin-dependent diabetes. PMID- 8348704 TI - Proinsulin, proinsulin intermediate and insulin in cystic fibrosis. AB - OBJECTIVE: We determined the changes in insulin, intact proinsulin and 32-33 split proinsulin as markers of beta cell damage in assessing the state of carbohydrate intolerance in patients with cystic fibrosis. DESIGN: Measurements of insulin, proinsulin and 32-33 proinsulin concentrations in cystic fibrosis following oral glucose tolerance test (OGTT). SUBJECTS: Sixteen cystic fibrosis patients attending the chest outpatient clinic for follow-up, age range 14-42 years, and 14 healthy controls matched for age and body mass index. MEASUREMENTS: Insulin, intact proinsulin and 32-33 split proinsulin were measured immunoradiometrically at 0, 30, 60, 90 and 120 minutes after an OGTT. Glucose and HbA1 were also measured. RESULTS: Cystic fibrosis patients were divided into two groups according to their OGTT results: those with diabetes mellitus or impaired glucose tolerance and those with normal glucose tolerance. Insulin concentrations and insulin/glucose ratios at 30 minutes were lower in both cystic fibrosis groups in comparison with the control. There was also a significant increase in the time to reach peak insulin levels in both cystic fibrosis groups. Fasting intact proinsulin concentrations and the proportion of proinsulin-like molecules were significantly higher in cystic fibrosis with diabetes mellitus or impaired glucose tolerance than in the control group, but not in the normal glucose tolerance cystic fibrosis group. There was no significant difference in the plasma concentrations of 32-33 split proinsulin amongst the three groups. CONCLUSIONS: Abnormal beta cell function in cystic fibrosis patients was reflected initially in a diminished 30-minute insulin response to oral glucose. A significant rise in fasting intact proinsulin and the proportion of proinsulin like molecules was seen only in cystic fibrosis patients who had progressed to impaired glucose tolerance or diabetes mellitus. Cystic fibrosis patients with normal glucose tolerance showed changes intermediate between the control and the other group. PMID- 8348705 TI - Elevated serum immunoreactive inhibin levels in peripubertal boys with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure (CSPCRF). AB - OBJECTIVE: Boys with chronic renal failure have delayed progress through puberty and have raised gonadotrophin and low testosterone levels indicative of disturbed hypothalamo-pituitary-testicular function. Most studies into the mechanisms underlying the dysfunction have concentrated on the LH-Leydig cell interaction. However, it is now possible to probe the FSH-Sertoli cell axis by measuring plasma immunoreactive inhibin, which is a marker of Sertoli cell function. This study investigated the FSH-Sertoli cell (immunoreactive inhibin) axis in boys with chronic renal failure on conservative and dialysis treatment as they progressed through puberty. The effect of renal transplantation in chronic renal failure was also investigated. DESIGN: Blood was drawn at 15-minute intervals between 2000 and 0700 h from 51 boys with chronic renal failure at various stages of puberty. The samples were divided into two pools, corresponding to the hormone secretion in the first and second part of the night. Single blood samples were drawn from a group of normal boys between 0800 and 1000 h. PATIENTS: A total of 37 normal boys and 51 boys with chronic renal failure were examined immediately before and during puberty. Of a total of 80 pulse profiles taken in chronic renal failure, 36 were from transplanted and 44 from non-transplanted uraemic subjects. MEASUREMENTS: Immunoreactive inhibin, FSH and testosterone were measured using standard radioimmunoassays. The subjects were pooled into pubertal stages I, II/III and IV/V for analysis of hormone data. RESULTS: Early morning levels of immunoreactive inhibin like molecules (i-Inh) rose steadily with pubertal progression for all subject groups, those for boys with chronic renal failure being significantly elevated over normal boys from pubertal stage II/III onwards. Uraemic boys had higher levels than those who had been transplanted at all pubertal stages (P < 0.05). Early morning levels of FSH were significantly higher in uraemic patients with pubertal stages IV/V compared to our normal boys. There were no differences in i-Inh levels in plasma pooled from the samples taken between 2000 and 0115 h and 0130 and 0700 h for either treatment group at any stage of puberty. Testosterone levels rose in the second part of the profile from pubertal stages II/III onwards for both treatment groups. The proportional increase of testosterone was lower by mid puberty in uraemic than in transplanted children (percentage increases of 92 +/- 29 and 569 +/- 190 respectively, mean +/ SEM). i-Inh failed to correlate with FSH at any Tanner stage or for any subject group. CONCLUSION: Peripubertal boys with chronic renal failure have highly elevated serum immunoreactive inhibin and FSH levels which are partially reduced by renal transplantation. There was no evidence of any relationship between i-Inh and FSH secretion in either normal boys or in uraemic or transplanted boys with the exception of a positive correlation in late pubertal patients after transplantation. Finally, despite problems associated with the current immunoassay for inhibin, this assay may still prove to be a useful marker of Sertoli cell function in testicular pathology. PMID- 8348706 TI - Premature ovarian failure: autoimmunity and natural history. AB - OBJECTIVE: We studied the association of clinical and latent autoimmune diseases with circulating steroid-producing cells autoantibodies (SCA) in patients with premature ovarian failure (Group I). We investigated the presence of SCA in patients with organ-specific autoimmune diseases but without hypogonadism (Group II). We assessed whether SCA can be considered markers of hypergonadotrophic hypogonadism. DESIGN: In Groups I and II blood samples were taken at diagnosis. In a subset of patients with SCA without hypogonadism blood samples were taken at least yearly for 6 years for immunological and functional tests. PATIENTS: Group I included 50 females, aged 16-39 years; Group II included 3677 patients, aged 6 79 years, divided into Subgroup IIA (99 with Addison's disease alone or associated with other endocrinopathies or with hypoparathyroidism) and Subgroup IIB (3578 with insulin-dependent diabetes mellitus or thyroid autoimmune diseases). The follow-up group included nine subjects, aged 5-31 years (seven females and two males). MEASUREMENTS: SCA and other organ-specific autoantibodies were detected by standard indirect immunofluorescence using normal human tissues or passive haemagglutination tests. Gonadal functional tests included evaluation of FSH and LH levels by a RIA method; adrenocortical function included evaluation of cortisol and ACTH plasma levels by a RIA method. RESULTS: Three subgroups were identified in Group I on the basis of clinical autoimmune disease. 9/50 (18%) patients were found to have an Addison's disease (Subgroup IA) and in this subgroup SCA were present in 7/9 (78%); 10/50 (20%) had other autoimmune diseases (Subgroup IB) and SCA were found in 1/10 (10%); 31/50 (62%) did not have other clinical autoimmune diseases (Subgroup IC) and 1/31 (3%) had SCA. SCA were significantly increased in Subgroup IA vs IB (P = 0.017) and vs IC (P = 0.00002). In Group II, SCA were found in 20/3677 (0.5%); in particular, SCA were detected in 18/99 (18%) of the patients in Subgroup IIA and in 2/3578 (0.06%) of the patients in Subgroup IIB. The frequency of SCA in Subgroup IIA was found to be significantly increased with respect to that found in Subgroup IIB (P = 0.001 x 10(-5)). During follow-up, 3/7 females (42.8%) but 0/2 males developed hypergonadotrophic hypogonadism with a latency period of 10, 13 and 15 years, respectively. Three females and two males lacked clinical Addison's disease at the beginning of the study, but during follow-up 1/3 female and 2/2 males developed clinical Addison's disease with a mean latency period of 13 months. CONCLUSIONS: The results confirm the strong relationship between premature ovarian failure and other clinical autoimmune diseases, as well as the strong link existing between primary ovarian failure, Addison's disease and antibodies to steroid-producing cells. The study also suggests that in females antibodies to steroid-producing cells are serological markers of both potential hypergonadotrophic hypogonadism, and Addison's disease; however, in males these antibodies may be considered only as markers of potential Addison's disease. PMID- 8348707 TI - Effect of varying concentrations of follicle stimulating hormone on the production of gonadotrophin surge attenuating factor (GnSAF) in women. AB - OBJECTIVE: We studied the time-course of production of gonadotrophin surge attenuating factor (GnSAF) in relation to varying serum concentrations of FSH in women. DESIGN: Normally cycling women were investigated in four cycles, i.e. a spontaneous cycle treated with placebo (cycle P) and three cycles treated with three different FSH dosages (1 ampoule, cycle 1; 3 ampoules, cycle 3 and 6 ampoules, cycle 6). Placebo or FSH were given as a single i.m. injection on cycle day 2 (0900 h). The response of LH to an i.v. injection of 10 micrograms GnRH (GnSAF bioactivity) was investigated 4, 8, 12 and 24 hours after the injection of placebo or FSH. PATIENTS: Six normally ovulating women with long-standing unexplained infertility were studied. The women were used as their own controls during the cycle treated with placebo. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in LH at 30 minutes (delta LH) above the basal value. RESULTS: Serum FSH concentrations increased after the injection of FSH in a dose dependent manner. Compared with cycle P, delta LH was significantly attenuated in cycle 3 and cycle 6 at 8, 12 and 24 hours and in cycle 1 at 12 hours after the injection of FSH. Basal concentrations of oestradiol (E2) and LH did not differ significantly among the four cycles at any point except in cycle 6 at 24 hours after the FSH injection when E2 values were significantly higher and LH values significantly lower than in cycle P. CONCLUSIONS: These results suggest that GnSAF bioactivity increases significantly as early as 8 hours from a single injection of FSH before any significant increase in serum E2 values. We conclude that in women the effect of FSH on the production of GnSAF in the early follicular phase is concentration dependent. PMID- 8348708 TI - Prevalence of subclinical hyperthyroidism and relationship between thyroid hormonal status and thyroid ultrasonographic parameters in patients with non toxic nodular goitre. AB - OBJECTIVE: Basal plasma T4, T3 and TSH concentrations are usually normal in patients presenting with non-toxic nodular goitre. Using the evaluation of TSH response to TRH in a large series of such patients living in an area with normal iodine intake, we evaluated the prevalence of subclinical hyperthyroidism and the relationship between thyroid hormonal status and ultrasonographic parameters. PATIENTS: A prospective study of 242 consecutive patients (group I), referred with non-autoimmune nodular goitre, normal plasma free T4, total T3 and TSH levels, without (subgroup IA, 222 patients) or with (subgroup IB, 20 patients) clear-cut autonomous area(s) on scintigraphy. These patients were compared to 135 controls (group II). MEASUREMENTS: Plasma free T4 (FT4), total T3 (T3T) and TSH measurements. Evaluation of TSH response to TRH (delta level of increased TSH = peak TSH level during TRH test-basal TSH level), thyroid scintigraphy and morphological characteristics (number and total volume of nodule(s) and volume of extranodular tissue) determined by ultrasonography. RESULTS: In subgroup IA, (1) the mean (+/- SEM) basal TSH level (0.94 +/- 0.04 mU/I) and the mean value of increased TSH after TRH (4.92 +/- 0.34 mU/I) were lower (P < 0.001) than in group II (1.28 +/- 0.05 mU/I and 7.24 +/- 0.25 mU/I, respectively). The prevalence of SH (delta level of increased TSH below the mean -3 SD in controls) was 17.2%; (2) the mean FT4 level and the mean T3T value were not different (P > 0.05) from those of group II. In subgroup IB, (1) the mean basal TSH level (0.57 +/- 0.11 mU/I) and the mean increment of TSH after TRH (2.81 +/- 0.62 mU/I) were lower (P < 0.001) than in subgroup IA. The prevalence of subclinical hyperthyroidism was 75.0%; (2) the mean FT4 level (17.2 +/- 0.9 pmol/I) was not different from that in group II. However, the mean T3T value (1.99 +/- 0.01 nmol/I) was higher (P < 0.001) than in group II (1.65 +/- 0.05). In group I, subgroup IA and IB, there were significant (P < 0.05, at least) correlations between the numbers of nodules and both basal TSH levels and delta values of increased TSH or FT4 levels or T3T values. No correlations were found between other ultrasonographic data and plasma thyroid parameters. CONCLUSIONS: This study demonstrates a high prevalence of subclinical hyperthyroidism in patients presenting with non-toxic nodular goitres and suggests that the number of nodules, but not their total volume, is an important factor in the development of this condition. PMID- 8348709 TI - Relation between phenotype and intra-cellular thyroid hormone effect in patients with altered peripheral thyroid hormone sensitivity. AB - OBJECTIVE: We wished to ascertain whether different phenotypic appearances in patients with altered cellular sensitivity to thyroid hormones were related to the type of altered intra-cellular thyroid hormone effect. DESIGN: Blood samples were obtained from two members of a family suffering from generalized thyroid hormone resistance (GTHR) for hormone assays and examination of the cellular thyroid hormone effect, and the results compared with results from other families with signs of altered peripheral thyroid hormone sensitivity. PATIENTS: Two members of a family with thyroid hormone resistance and nine normal persons were studied. MEASUREMENTS: Basal thyroid hormone function tests were measured. The thyroid hormone effect on mononuclear blood cells was determined by measuring the thyroid hormone stimulated oxygen consumption and glucose uptake. RESULTS: The two family members appeared phenotypically normal except for nodular goitre. Thyroid hormone stimulated glucose uptake was depressed whereas thyroid hormone stimulated oxygen consumption was normal. CONCLUSION: Comparison of the present results of the cellular examination in two patients with GTHR, with the results obtained in other families with altered peripheral thyroid hormone sensitivity, suggest that the classic GTHR (phenotype: normal or with goitre) is linked to impaired thyroid hormone stimulated glucose uptake, whereas in patients with osteopetrosis, the thyroid hormone insensitivity seems located at the mitochondrial level (impaired thyroid hormone stimulated oxygen consumption. PMID- 8348710 TI - Effects of growth hormone therapy on the developmental changes of follicle stimulating hormone and insulin-like growth factor-I serum concentrations in Turner's syndrome. AB - OBJECTIVE: The aim was to investigate whether, in the absence of gonads, GH could bring forward the age of neuroendocrine activation resulting in onset of puberty. DESIGN: In girls with Turner's syndrome, we evaluated the effects of GH therapy on developmental changes in FSH serum concentrations used as an indicator of neuroendocrine maturation in the absence of gonads. PATIENTS: Thirty-nine girls with Turner's syndrome aged 4.0-17.1 years were treated using GH (25 IU/m2 week) for 1 year. MEASUREMENTS: Serum levels of FSH and IGF-I were measured before initiation of GH therapy and 12 months later, after interruption of GH treatment for 2 days. RESULTS: Pretreatment FSH levels were low between 6 and 10 years and increased markedly at 10-11 years of age. This pattern was unchanged after 1 year of GH therapy. Pretreatment IGF-I levels were positively correlated with age and they were uniformly increased after 1 year of GH therapy. CONCLUSIONS: Our data suggest that GH and its effector, IGF-I, do not influence the timing of the onset of puberty through an effect on its neuroendocrine control. PMID- 8348711 TI - An audit of dynamic function tests: errors in the timing of blood specimens. AB - OBJECTIVE: The interpretation of dynamic endocrine investigations is dependent on the timing of blood sampled after a stimulus. We have studied the accuracy with which doctors adhered to a prescribed protocol. DESIGN: A new request form for dynamic tests was designed to include both the planned and the actual time of blood sampling in order to allow assessment of the variance of sample timing. MEASUREMENTS: We followed 152 investigation procedures comprising 791 planned specimens. A total number of 627 timing intervals could be analysed of which 366 timing intervals did not differ from the planned interval. Protocols were divided into long and short (greater or less than 6 hours) and into those governed by clock times or 'stopwatch', i.e. minutes elapsed, intervals. RESULTS: A total of 22% specimens were taken more than 10 minutes earlier or later than planned. Six per cent of specimens were taken more than 30 minutes earlier or later than planned. CONCLUSIONS: The data presented in this study suggest that in order to improve the interpretative accuracy of dynamic tests, it would appear prudent to pay more attention to the accuracy of sample timing. New dynamic test publications should include time tolerance for the normal response. PMID- 8348712 TI - Performing a factory visit. PMID- 8348713 TI - Development and isotype diversity of antibodies to inhalant and dietary antigens in childhood atopic eczema. AB - This study demonstrated that a major feature of childhood atopic eczema (AE) is the presence of serum IgG and IgE anti-house dust mite (anti-HDM) antibodies in almost all AE individuals. IgG anti-HDM antibodies, usually of the IgG1 isotype, became prevalent in AE children over the age of 4 years with the highest antibody levels in children in their early teens. In contrast, immunological sensitization to dietary antigens, notably milk and eggs, occurred in both AE children and age matched non-atopic control children, and was often associated with IgG4 antibodies during early childhood. These became less prevalent with increasing age in control children but persisted in AE children, sometimes together with IgE antibodies. The later occurrence of anti-HDM antibodies in AE children could reflect immunological sensitization following inhalation of antigen, whereas sensitization to dietary antigens appears to be a natural event in early childhood. PMID- 8348714 TI - A wound healing model with sonographic monitoring. AB - The methods used hitherto for quantification of skin repair processes only allow an examiner a two-dimensional assessment of superficial wound healing. With the recent advent of high frequency B-scan ultrasonography in dermatology it has become possible to follow the course of healing and evaluate the healing processes in deeper layers of the skin. In this investigation 80 patients received cryosurgery for treatment of basal cell carcinomas on the face or neck region. As the size of cryosurgical defects can be precisely controlled they are potentially useful as standardized wound healing models. The course of wound healing after cryosurgery using a digital ultrasound scanner (DUB 20, Taberna pro medicum, Luneburg, Germany) was monitored. The usable depth of penetration of the echo signal is approximately 7 mm. The lateral resolution is approximately 200 microns, the axial resolution approximately 80 microns. The cryolesion and the repair processes were examined ultrasonographically and clinically over a period of at least 3 weeks or until the wound had completely healed. The depth of invasion and lateral extent of the basal cell carcinoma as well as the size of the induced cryolesion can be determined by ultrasound. The exudative phase after cryosurgery, with developing oedema and necrosis, can be quantified on the basis of the reduced reflectivity in the corium. The repair processes taking place in the region of necrosis can be visualized in the ultrasound scan. The ultrasonically monitored wound healing model which we have demonstrated is particularly suitable for investigating the efficacy of drugs which promote healing. PMID- 8348715 TI - IgG subclasses in pemphigus in Indian and UK populations. AB - The autoimmune blistering disease pemphigus is more common in the Indian subcontinent than in the UK. This study of 19 patients from Oxford, UK and 39 patients from New Delhi, India demonstrates that the incidence of the disease subtypes is different in the two countries. In the UK the commonest subtypes are pemphigus vulgaris and foliaceus with equal prevalence (both eight of 19), but in India pemphigus vulgaris is the most frequent (31 of 39), while pemphigus foliaceus is uncommon (three of 39) and with equal prevalence to the other subtypes. These populations also differ with a younger age at onset in the Indian patients (36.9 India; 52.7 UK) though the sex distribution is the same. Study of the immunopathology shows that the antibodies produced by patients in the two countries do not differ significantly, and are predominantly of the IgG4 subclass. The antibody produced does not vary with the subtype of pemphigus or the age or sex of the patient. Although there are considerable differences between the two groups of patients this difference is not reflected by the subclass of auto-antibody response. PMID- 8348716 TI - Adherence of arthroconidia and germlings of anthropophilic and zoophilic varieties of Trichophyton mentagrophytes to human corneocytes as an early event in the pathogenesis of dermatophytosis. AB - The association (adherence) between human corneocytes and arthroconidia of Trichophyton mentagrophytes strains 121 and 126, and T. interdigitale strain 4 was studied in vitro. Adherence of arthroconidia to corneocytes from either the palm and sole occurred and increased with time up to 6 h, by which time germination of arthroconidia had started. Significant differences were seen between the T. mentagrophytes strains and T. interdigitale in their adherence to corneocytes from the palm. When adherence values for plantar corneocytes were compared, significant differences were found between T. mentagrophytes and T. interdigitale. Not all corneocytes from either site had adherent arthroconidia, although there was a time-dependent increase in the numbers of corneocytes with adherent fungal cells. By scanning and transmission electron microscopy it was seen that there was a loose association between arthroconidia and corneocytes with no apparent damage to the corneocyte membrane. Adherence of germlings of T. interdigitale to corneocytes from the palm appeared to be mediated by germling outer cell wall fibrils. Hyphal branches and secondary germlings were observed to enhance the attachment of the parent hypha to adjacent corneocytes. PMID- 8348717 TI - Modulation of morphological differentiation of human endothelial cells in culture by the synthetic peptide YIGSR and cytochalasin B. AB - Matrigel is a solubilized tissue basement membrane gel extracted from the mouse Engelbreth-Holm-Swarm sarcoma. Cultures of human endothelial cells could be induced to undergo extremely rapid morphological differentiation into capillary like structures by Matrigel. The present study demonstrates the following: (a) Matrigel-induced tube formation by endothelial cells is laminin-dependent and, particularly, the YIGSR peptide site in the B1 chain of laminin may be necessary for endothelial cell differentiation resulting in capillary formation; (b) endothelial cells may be preprogrammed for rapid differentiation into blood vessels and do not require DNA, RNA or protein synthesis in order to undergo tube formation on Matrigel; and (c) microfilament assembly and function is important for Matrigel-induced tube formation. PMID- 8348718 TI - On naevi and melanomas in dysplastic naevus syndrome patients. AB - Cutaneous melanoma may occur as isolated, so-called 'sporadic' cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20-39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12-66 years. Men had significantly more naevi of a size > or = 2 mm or > or = 5 mm on the back than women (P = 0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and site in familial DNS, analogous to earlier reports on sporadic melanoma. PMID- 8348719 TI - Aquagenic pruritus associated with juvenile xanthogranuloma. AB - While the relationship of aquagenic pruritus (AP) to haematoproliferative conditions is well-recognized, an association with histiocytic disorders has not previously been described. The case of a child with both AP and juvenile xanthogranulomata (JXG) is reported. The cutaneous lesions were typical of JXG, both clinically and histologically, and in addition there were radiological changes consistent with JXG in the lungs. AP is rare in childhood and the coincidental occurrence with unusually extensive JXG seems unlikely. PMID- 8348720 TI - Actinic comedonal plaque--a rare ectopic form of the Favre-Racouchot syndrome. AB - A 59-year-old woman with a single cuff-like plaque, consisting of multiple skin coloured to bluish cysts and comedones on her right forearm is reported. The solitary lesion resembled, morphologically and histologically, the Favre Racouchot syndrome. The above condition is another case of the previously described actinic comedonal plaque, which seems to be a rare entity within the spectrum of disease caused by actinic damage to the skin. PMID- 8348721 TI - Plane xanthomatosis with chronic lymphatic leukaemia. AB - A case of plane xanthomatosis in a 67-year-old woman, suffering from chronic lymphatic leukaemia, who developed asymptomatic yellow plaques on the neck, upper arms and chest is reported. Histology was suggestive of xanthelasma. Development of plane xanthomata has been reported in association with various haematological malignancies and with benign monoclonal gammopathies, but not previously with chronic lymphatic leukaemia. PMID- 8348722 TI - Multiple minute digitate hyperkeratoses. AB - A case of non-familial multiple digitate hyperkeratosis is reported. Digitate hyperkeratosis is a new, non-follicular disorder of keratinization and three different types have been distinguished in the literature: the familial type, with an autosomal dominant trait; the sporadic type; and the post-inflammatory type. PMID- 8348723 TI - Centroblastic transformation of chronic lymphocytic leukaemia with primary skin involvement--cutaneous presentation of Richter's syndrome. AB - The development of a large-cell non-Hodgkin's lymphoma in a patient suffering from chronic lymphocytic leukaemia is known as Richter's syndrome, representing one of the possible anaplastic transformations of the leukaemia. Cutaneous involvement is an extremely rare event. The case of a 45-year-old man with B-cell chronic lymphocytic leukaemia is reported. Five years later multiple cutaneous nodules developed on his extremities. Biopsies of the skin showed a diffuse large cell lymphoma, bearing the same cell surface immunoglobulin light chain isotype as the leukaemia, suggesting the original relationship between both neoplasms. PMID- 8348724 TI - Acquired ichthyosis and pyoderma gangrenosum in a patient with systemic lupus erythematosus. AB - A 25-year-old woman who was 20 weeks pregnant developed systemic lupus erythematosus with acquired ichthyosis and pyoderma gangrenosum. The course of these dermatoses suggests that an immunopathological mechanism was implicated in their pathogenesis. PMID- 8348725 TI - Neonatal lupus erythematosus with persistent telangiectasia and spastic paraparesis. AB - A case of neonatal lupus erythematosus with cutaneous and neurological features is reported. At 5 years of age, the patient retains residual telangiectatic lesions over the trunk and face and has mild spastic diplegia, originally detected at the age of 1 year. Persistent telangiectasia is now a recognized feature of neonatal lupus erythematosus. The pathogenesis of the neurological deficit is uncertain. PMID- 8348726 TI - Atypical Nekam's disease--keratosis lichenoides chronica associated with porokeratotic histology and amyloidosis. AB - A patient with atypical Nekam's disease is described. Although the histological appearances were lichenoid, the presence of porokeratosis and amyloid deposition, previously reported in this condition, argue against the view that Nekam's disease is a subset of lichen planus. PMID- 8348727 TI - Waldenstrom's macroglobulinaemia presenting with cold urticaria and cold purpura. AB - A case of Waldenstrom's macroglobulinaemia presenting with non-specific dermatological symptoms (cold urticaria and cold purpura) is described in a 37 year-old female patient. Progressive telangiectasia and spider naevi were also observed. Involvement of the skin may be explained by the presence of macroglobulins with cryoprotein-like qualities. This facilitated an early diagnosis. PMID- 8348728 TI - Benign cephalic histiocytosis--study of a case. AB - Benign cephalic histiocytosis is a rare, benign, self-healing form of non-X histiocytosis. A case in a 3-month-old girl is reported. The papular eruption involved her face, neck, shoulders and upper trunk. Light and electron microscopic findings and clinical evolution confirmed the diagnosis. The differential diagnosis with the micronodular form of juvenile xanthogranuloma is discussed. PMID- 8348729 TI - Familial erythromelanosis follicularis faciei et colli--an autosomal recessive mode of inheritance. AB - Two cases of erythromelanosis follicularis faciei et colli in one family, affecting a brother and sister are described. In these cases erythromelanosis follicularis faciei et colli, a process of unknown aetiology, seems to have a clear hereditary component--autosomal recessive mode of inheritance--a feature which, as far as we know, has not been reported in the literature. PMID- 8348730 TI - Secondary localized cutaneous amyloid in Bowen's disease. AB - A case of Bowen's disease is described in which striking quantities of amyloid were detected in the papillary dermis visualized easily by routine haematoxylin and eosin staining. The material showed positive labelling with an antikeratin monoclonal antibody consistent with the proposed origin of the amyloid as degenerate keratinocytes. The pathobiology of amyloid associated with dysplastic squamous lesions is discussed. PMID- 8348731 TI - Milia cysts along the nasal groove in a child. AB - The occurrence of transverse linear milia cysts over the dorsum of the nose in an 11-year-old girl is described. Two younger sisters of the proband had a conspicuous nasal groove at the same site without milia. The anatomical basis and the pathogenesis of the so-called 'transverse nasal crease' are reviewed. PMID- 8348732 TI - Bedding and eczema. PMID- 8348734 TI - Oral retinoids to treat black hairy tongue. PMID- 8348733 TI - How to reduce the discomfort caused by local anaesthetics. PMID- 8348735 TI - Phototoxicity at unusual sites during photochemotherapy. PMID- 8348736 TI - Bullous pemphigoid-like scabies. PMID- 8348737 TI - Twenty-nail dystrophy due to lichen planus in a patient with alopecia areata. PMID- 8348738 TI - Pitfalls in the measurement of soluble forms of cell surface receptors. PMID- 8348739 TI - Elevated serum levels of IL-8 in patients with HIV infection. AB - Serum levels of IL-8 were determined in HIV-infected individuals and the results were compared with those for HIV- controls. The IL-8 levels were measured by an ELISA with a MoAb and a polyclonal antibody to recombinant IL-8. The means and 95% confidence intervals of IL-8 in sera of 36 HIV-infected individuals and 32 matched controls were 275 and 216-349 pg/ml, and 8 and 4-14 pg/ml, respectively, showing a 34-fold increase in IL-8 in the circulation of HIV-infected individuals. This increase does not appear to be related to the disease state, infection or systemic medical agents. This finding suggests the possible involvement of IL-8 in the pathogenesis of HIV-induced disease. PMID- 8348740 TI - The acquisition of anti-pneumococcal capsular polysaccharide Haemophilus influenzae type b and tetanus toxoid antibodies, with age, in the UK. AB - Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and to tetanus toxoid (TT), were measured in serum samples of 750 age-stratified subjects from the UK. The study subjects comprised healthy adult volunteers and hospitalized children undergoing elective surgery, excluding those with a history of infection or under investigation for immunological or haematological disorders. These antibody levels were calibrated by comparison with serum pool obtained from healthy adult volunteers, who were immunized with Hib polyribose-phosphate vaccine (Merieux). The data are intended to provide reference ranges to assist in the interpretation of specific antibody measurements in the clinical setting. Maternal IgG pneumococcal capsular polysaccharide (PCP) specific antibody levels, geometric-mean titre (GMT) 1/22, were lost by 6 months of age (GMT of 1/9). They remained low until 3-5 years (GMT of 1/20), and consisted principally of IgG1. Thereafter, IgG anti-PCP antibody titres increased steadily to adult levels (GMT of 1/275), of which 80% was IgG2. Anti-PCP antibody titres of the IgM isotype rose steadily from a GMT 1/21 (0-6 months) to 1/420 (3-5 years), a level which was maintained until adulthood. Anti Hib antibody concentrations, determined by RABA, again demonstrated the decline in maternal antibody, from 0.18 micrograms/ml in the 0-6 month age cohort, to 0.09 microgram/ml between 6 and 12 months. Geometric-mean antibody concentrations remained below 0.2 micrograms/ml until 3-5 years, then increased with age, attaining the mean adult level of 1.02 micrograms/ml. Anti-TT antibody concentrations were measured in the same sera, by ELISA. Two peaks in anti-TT antibody levels were seen in children of 0.059 IU/ml and 0.166 IU/ml corresponding to the schedule of routine childhood immunization in the first year and at 5 years of age. PMID- 8348741 TI - Treatment of murine macrophages with murine interferon-gamma and tumour necrosis factor-alpha enhances uptake and intracellular killing of Pseudomonas aeruginosa. AB - Murine interferon-gamma (MuIFN-gamma) and murine tumour necrosis-alpha (MuTNF alpha) are known to be potent immunomodulators of several aspects of the immune response, and they have been shown to exert profound effects on macrophages and monocytes. The purpose of this study was to determine the effects of MuIFN-gamma and MuTNF-alpha on the phagocytosis (uptake and intracellular killing) of opsonized Pseudomonas aeruginosa. Unstimulated peritoneal macrophages obtained from CBA/c mice were exposed to different concentrations of recombinant forms of the cytokines (rMuIFN-gamma and rMuTNF-alpha) for different periods of time. Phagocytosis was assayed using different concentrations of opsonized Ps. aeruginosa. In all cases the pretreatment of the cells with the cytokines increased significantly the uptake and the intracellular killing of bacteria in a dose-dependent manner. rMuTNF-alpha was effective only at 1000 U/ml. Combined treatment with the cytokines showed a less than additive effect with rMuIFN-gamma and rMuTNF-alpha at concentrations of 10 U/ml and 100 U/ml. In the in vivo experiments, peritoneal macrophages obtained from rMuIFN-gamma- or rMuTNF-alpha treated mice showed enhancement of the intracellular killing of opsonized bacteria in a dose-dependent manner. PMID- 8348742 TI - Elevation of heat shock protein synthesis and hsp gene transcription during monocyte to macrophage differentiation of U937 cells. AB - During the phorbol myristate acetate (PMA)-induced differentiation of U937 cells to a macrophage-like phenotype, the levels of the heat shock proteins hsp90, hsp72 and hsp65 increased dramatically to a peak level following 24 h of treatment, and then declined. In contrast, no significant increase was observed in the level of the constitutive hsp73 protein in this process. The observed increases in hsp levels were preceded by an increase in the transcription of each of the genes encoding these hsps, including both of the two genes which encode hsp90. The mechanism of this effect and the possible role of the hsps in the function of differentiated macrophages and in the differentiation process are discussed. PMID- 8348743 TI - Tumour necrosis factor production in vivo and in vitro in response to Paracoccidioides brasiliensis and the cell wall fractions thereof. AB - Tumour necrosis factor (TNF) was detected in serum from mice challenged with Paracoccidioides brasiliensis. The serum TNF levels of mice challenged with an avirulent strain were significantly higher than those of mice challenged with a virulent strain, and the same was observed for the TNF levels of mice challenged with a cell wall fraction (F1) from the two fungal strains. Fraction F1 consisted of chitin and beta-glucan; but although the chitin contents were similar for the two strains, the avirulent strain allowed a greater content of beta-glucan. The beta-glucan, purified from both strains, increased serum TNF levels in an identical dose-dependent manner, whereas purified chitin did not induce serum TNF levels. P. brasiliensis, the F1 fractions and beta-glucan induced macrophages to secrete TNF in vitro. The differences in TNF levels, induced by the different fungal strains, were correlated with the beta-glucan concentrations in the cell walls of both the avirulent and virulent strains of P. brasiliensis. These findings support a role for TNF in the pathogenicity of P. brasiliensis. PMID- 8348744 TI - Determination of soluble CD21 as a parameter of B cell activation. AB - In this study we established a novel solid-phase immunoassay for CD21 using the time-resolved fluorescence of lanthanide chelates. The capture assay was able to detect concentrations of as low as 100 pg of CD21 antigen per millilitre of sample and was used for quantitative determination of CD21 in lysates of different cell lines as well as in patient serum specimens. CD21 was measured in lysates of tonsils and cell lines of B, T cell and myelomonocyte lineage, and appeared to consist of monomeric antigen under the detergent conditions used. Elevated levels of soluble CD21 were observed in serum of patients with Epstein Barr virus (EBV) infection, a disease known to be associated with polyclonal B cell activation, and in infection with the lymphotropic rubella virus. Significantly increased levels were also found in malignancies which are associated with EBV. In patients with nasopharyngeal carcinoma (NPC), a correlation with the titre of EBV-specific IgA was observed, thus supporting a possible role of soluble CD21 as a marker for disease activity in certain malignancies. Our data suggest that measurement of soluble CD21 could serve as a marker for activation of the immune system and diseases involving the B cell lymphoid system. Possible mechanisms and functions of soluble CD21 are discussed. PMID- 8348745 TI - Production of IL-1 and IL-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits. AB - Injection of lipopolysaccharide (LPS) into rabbit knee joints provoked leucocyte infiltration and loss of proteoglycan (PG) from the cartilage. We investigated the role of IL-1 and IL-1 receptor antagonist (IL-1Ra) and its significance in the pathogenesis of LPS-arthritis. Production of IL-1 beta peaked at 6 h (196.7 +/- 89.4 pg/joint) after injection of 10 ng of LPS, while IL-1Ra peaked at 9 h (34.5 +/- 13.4 ng/joint). The amount of IL-1Ra was 180-200-fold molar excess of IL-1, and a large amount of IL-1Ra was sustained for 1 week. Both IL-1 beta and IL-1Ra were mainly produced by synovial exudate cells. Arthritis was reproduced by rabbit IL-1 beta. LPS-induced leucocyte infiltration was inhibited 70-75% by rabbit IL-1Ra. Loss of PG in LPS-arthritis was prevented by IL-1Ra and also by neutrophil elastase inhibitor, and superoxide dismutase. In leucopenic rabbits, injection of LPS induced neither production of IL-1 beta nor loss of PG. Direct injection of inflammatory exudated cells in leucopenic rabbits reproduced loss of PG, and there was only a partial recovery by IL-1Ra. These results suggest that LPS-initiated IL-1 acts as a key mediator in LPS-arthritis and that endogenous IL 1Ra may suppress a part of IL-1 activity at the site, but its amount was too low for suppression of the produced IL-1. Loss of PG is a sequela of infiltrated leucocytes and leucocyte-derived elastase, and superoxide anion may play a pivotal role in the destruction of cartilage. PMID- 8348747 TI - Early induction of IL-1 receptor antagonist (IL-1Ra) in infants and children undergoing surgery. AB - The cytokine response to injury or trauma is of interest in terms of both its mediation of the acute phase response and its possible relation to the immunological depression observed after major surgery. In this study, the production of cytokines IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and the naturally occurring inhibitor of IL-1, IL-1Ra, have been investigated in infants and children undergoing Swenson's pull-through operation for Hirschsprung's disease. Samples of peripheral blood were taken before, during and after surgery for the measurement of cytokines. IL-1Ra levels increased significantly (P < 0.01) at 2 h after commencement of surgery, with maximal levels for individual patients being attained between 3 h and 5 h (range 7.6-67.9 ng/ml). The mean level of IL-1Ra was maximal (26.2 ng/ml) at 5 h and returned to baseline levels between 24 h and 72 h. There were no changes observed in the circulating levels of IL-1 beta in nine out of 11 patients following commencement of surgery. TNF-alpha levels did not increase in any of the patients studied. IL 6 levels increased significantly (P < 0.02) 3 h after commencement of surgery, reaching maximum concentrations at 24 h (range 20-670 pg/ml), with levels falling between 48 h and 72 h. This study demonstrates, in vivo, the independent induction of IL-1Ra without a concomitant increase of IL-1 beta levels after major surgery. It also shows that IL-1Ra is the earliest cytokine produced in response to surgical stress. PMID- 8348746 TI - IL-2 enhances polyclonal IgM but not IgM-rheumatoid factor synthesis by activated human peripheral blood B cells. AB - IgM-rheumatoid factor (RF) is thought to be involved in the pathogenesis of rheumatoid arthritis (RA). Several cytokines are known to regulate immunoglobulin synthesis. In this study the effects of IL-2 on polyclonal IgM and IgM RF synthesis were compared. Cytokines were added to peripheral blood B cells from normal subjects and patients with RA after activation by Staphylococcus aureus Cowan 1 (SAC). The addition of IL-2, but not IL-4 or IL-6, resulted in significant enhancement of IgM synthesis in cultures from both healthy subjects and patients with RA. Similar degrees of enhancement were seen in both peripheral blood mononuclear cell and highly purified B cell cultures. IgM-RF was synthesized after activation in cultures from healthy subjects and spontaneously in cultures from RA patients. In contrast to polyclonal IgM synthesis, IL-2 failed to augment IgM-RF synthesis in cell cultures from either healthy subjects or RA patients. This study demonstrates different effects of IL-2 on IgM and IgM RF synthesis. PMID- 8348748 TI - Immunohistochemical detection of co-localizing cytokine and antibody producing cells in the extrafollicular area of human palatine tonsils. AB - In vitro experiments have documented the role of cytokines in the regulation of the human humoral immune response. Which cytokines are operative in vivo and in which lymphoid compartment interactions between cytokine-producing T cells and antibody-forming B cells occur is still unclear. For that reason we studied human tonsils using immunohistochemical techniques. In tissue sections from tonsils in a resting stage after recurrent tonsillitis we observed cells producing IL-1 alpha and tumour necrosis factor-alpha (TNF-alpha) which were exclusively localized in the mantle zone of the follicle and in the extrafollicular area. Furthermore, a high frequency of interferon-gamma (IFN-gamma)-producing cells was detected in the extrafollicular area, but not inside the follicles. Occasional IL 2- and IL-4-producing cells were found in the extrafollicular area. Immunohistochemical detection of antibody isotypes revealed that B cells, IgM membrane-positive, were localized inside the follicles and mantle zones, whereas IgD-membrane-positive cells were mainly found in the mantle zones of secondary follicles. In contrast, plasma cells producing IgG1-4 and IgA1-2 were found in the extrafollicular area. No IgD and IgE antibody-forming cells were detected in tonsils, whereas IgM antibody-forming cells were detected in the extrafollicular area. The co-localization of cytokine-producing cells and antibody-forming cells in human tonsil suggests that T-B cell interactions, required for B cell differentiation and isotype switching, take place in the extrafollicular area. PMID- 8348749 TI - Effects of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and monocytes on lymphokine-activated killer (LAK) induction from natural killer (NK) cells and T lymphocytes. AB - Roles of monocytes and cytokines were investigated on LAK induction from T and NK cells. Monocytes augmented more T-LAK induction than did NK-LAK. Expression of IL 1 beta, TNF-alpha and interferon-gamma (IFN-gamma)-mRNA and their cytokine production were superior in NK cells compared with T cells in parallel with their LAK activities. An increase of TNF-alpha, IL-1 beta and IFN-gamma production was induced by co-culturing NK or T cells with autologous monocytes. The augmentation of T cell cytokine production and T-LAK activity by monocytes was more prominent than that of NK cells. TNF-alpha and IL-1 beta were generated 24 h after IL-2 stimulation, and these cytokines were able to almost substitute for monocytes in LAK induction. Conversely, LAK induction was almost completely suppressed by both anti-IL-1 beta and anti-TNF-alpha antibodies, if they were added within 24 h after the start of the LAK induction. IFN-gamma, which was produced at a later stage, scarcely affected LAK induction in spite of the cooperation with TNF alpha. The results obtained indicate conclusively that the superiority of NK-LAK depends on their superior productivity of both IL-1 beta and TNF-alpha, and that the up-regulation of LAK induction by monocytes is largely due to the enhanced generation of both cytokines. PMID- 8348750 TI - Clustering of neutrophil leucocytes in serum: possible role of C1q-containing immune complexes. AB - Clustering activity for neutrophil granulocytes was generated in pooled normal human serum (NHS) by incubation of the serum with preformed IgG aggregates, but not in heat-treated NHS (56 degrees C, 30 min), indicating that the function was complement-dependent. Judging from results of experiments with complement deficient sera, and serum depleted of C1q, factor D and properdin, recruitment of the complement system beyond C1 was not required for induction of the activity. Zymosan treatment of NHS resulted in some neutrophil clustering activity, but recombinant C5a had a limited effect. C1q added to heat-treated NHS in conjunction with performed IgG aggregates supported neutrophil clustering in a dose-dependent manner. The serum C1q inhibitor, a chondroitin 4-sulphate proteoglycan known to interact with the collagenous part of C1q, clearly reduced neutrophil clustering in heat-treated NHS supplemented with C1q and IgG aggregates. The C1q inhibitor also reduced the inherent neutrophil clustering activity of some sera from patients with systemic lupus erythematosus (SLE). Neutrophil clustering activity in SLE serum was earlier shown to be inversely related to the number of circulating neutrophils in vivo. Although the precise mechanisms remain unclear, we propose that C1q-containing immunoglobulin complexes mediate neutrophil clustering through C1q receptors, and that this might contribute to pathogenesis of immune complex diseases such as SLE. PMID- 8348751 TI - Elevated complement activities of sera from patients with high density lipoprotein deficiency (Tangier disease): the presence of normal level of clusterin and the possible implication in the atherosclerosis. AB - Clusterin (apolipoprotein J, SP-40,40), as well as apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II), are apolipoprotein components of high density lipoprotein (HDL), but not of low density lipoprotein. In spite of the deficiencies of apo A-I, apo A-II and HDL in the sera of patients with Tangier disease, clusterin was found in them at normal level. While clusterin was present as the component of HDL with apo A-I in sera of normal donors, it was present as a protein which did not form a complex in sera of Tangier patients. SC5b-9 made from the sera of Tangier patients contained normal amounts of clusterin and was deficient in apo A-I, indicating that clusterin could be incorporated into the SC5b-9 complex without apo A-I. The complement activities of the sera of the patients were higher than those of normal donors. These results may be explained by the deficiencies of apo A-I, apo A-II and HDL in the patients, because they were suggested to be the inhibitors of the reactive haemolysis of complement. The elevated complement activities of the patients might be related to the severe atherosclerotic lesions in Tangier disease. PMID- 8348752 TI - Trichosanthin, an initiator of the alternative complement activation pathway. AB - Trichosanthin (TCS), a protein purified from the plant Trichosanthes Kirilowii Maxim, activates normal human serum complement via the alternative pathway, as shown by TCS-induced C3 conversion in normal serum and its prevention by depletion of factor B, but not with the addition of EGTA. Injection of TCS to BALB/c mice consumed the complement alternative pathway (APC) activity in serum, implying in vivo activation of the alternative pathway by TCS. Elevation of peripheral blood leucocyte count as well as protein exudation and neutrophil accumulation in the peritoneal cavities could be induced by peritoneal injection of TCS. The main effect of complement activation by TCS was demonstrated to be induction of neutrophil accumulation. PMID- 8348753 TI - Antimitochondrial autoantibodies in anti-glomerular basement membrane disease. AB - Anti-glomerular basement membrane (GBM) disease is characterized by the production of an autoantibody with very restricted specificity, with no evidence of polyclonal B cell activation. It was therefore surprising to find that in a solid-phase ELISA a proportion of anti-GBM sera showed significant binding to pyruvate dehydrogenase (PDH), a reactivity usually associated with the antimitochondrial autoantibodies (AMA) found in primary biliary cirrhosis (PBC). The specificity of this reactivity was confirmed by inhibition and competition experiments. The AMA found in anti-GBM sera were of much lower affinity than those found in PBC sera, and recognized a more restricted set of species (mainly the 55-kD and occasionally the 74-kD component of PDH). However, it was possible to block the binding in a Western blot of an anti-GBM serum to both the 55-kD and 74-kD species with F(ab')2 fragments prepared from a PBC serum. Although AMA have been found in diseases other than PBC, such diseases have usually been characterized by polyclonal B cell activation. The stimulus to the production of AMA in anti-GBM disease, and their significance in pathogenesis (if any), are unknown. PMID- 8348754 TI - Inhibitor(s) of natural anti-cardiolipin autoantibodies. AB - IgG fractions were purified on Sepharose anti-human IgG column from eight sera of healthy donors, having no anti-cardiolipin (aCL) activity as measured by anti cardiolipin ELISA assay (aCL-ELISA). All the IgG fractions, after elution with 4.9 M MgCl2, reacted with CL. The antigen-binding characteristics of the IgG fractions purified from normal human serum (NHS) were similar to those of IgG fractions purified from sera of four patients with the anti-phospholipid syndrome (APLS). Competition assay confirmed the specificity of the binding of the purified IgG fractions to CL. The same results have been achieved with IgG fractions purified on Sepharose Protein-A column. The binding to CL was completely inhibited by either whole NHS and sera from various animal species, or by beta 2-glycoprotein I (beta 2-GPI). Our results support the notion of the existence of both natural anti-CL antibodies and serum inhibitor(s) in sera of healthy individuals. It is conceivable that in part the pathogenesis of APLS entails defects in the natural inhibitors of aCL antibodies. PMID- 8348755 TI - Induction of phospholipid-binding antibodies in mice and rabbits by immunization with human beta 2 glycoprotein 1 or anticardiolipin antibodies alone. AB - Anticardiolipin (aCL) antibodies are autoantibodies present in high concentrations in patients with the antiphospholipid syndrome (APS), a disorder of recurrent thrombosis and pregnancy loss. What induces aCL antibodies is uncertain, but a recent report suggested that immunization of mice with beta 2 glycoprotein 1 (beta 2 GP1) in Freund's complete adjuvant (FCA) resulted in aCL antibody production in the recipient mice. Since this observation might explain how autoantibodies might be induced by poor immunogens, such as phospholipids, we decided to explore the question further. In our first series of experiments, we found that aCL antibodies were induced in mice by beta 2GP1 mixed with adjuvants that did not contain lipids (Adju-Prime or aluminium hydroxide). This excluded the possibility that antibody induction occurred because beta 2GP1 formed complexes with lipids in FCA. We also found that aCL antibodies always appeared before anti-beta 2GP1 antibodies, excluding the possibility that aCL antibodies were directed to beta 2GP1 or were induced by formation of anti-idiotypic antibodies (to anti-beta 2GP1). In experiments, we found that immunization of mice with human IgG antibodies from patients with the APS (IgG-APS), also induced aCL antibodies. Immunization with pure bovine serum albumin (BSA) did not induce aCL antibodies. We propose that aCL antibodies are induced by proteins with high avidity for phospholipids. These proteins may be bound to phospholipids when introduced, or may bind circulating phospholipids, so transforming phospholipid molecules into immunogens. Similar mechanisms might explain autoantibody induction to other poor immunogens. PMID- 8348756 TI - Protection of islet cells from inflammatory cell death in vitro. AB - Islet cells cocultured with activated macrophages are lysed within 15 h in vitro. We showed previously that nitric oxide generated by macrophages is a major mediator of islet cell death. We have now probed several pathways to interfere with the chain of events leading to islet cell death. Scavenging of extracellular oxygen radicals by superoxide dismutase and catalase did not improve islet cell survival. Scavenging of extra- and intracellular oxygen radicals by two potent substances, citiolone and dimethyl-thiourea, also did not reduce islet cell lysis, while a lipid-soluble scavenger, probucol, provided partial protection. These findings argue against a synergistic action of nitric oxide and oxygen radicals in islet cell toxicity. The inhibition of poly(ADP-ribose)polymerase by 3-aminobenzamide significantly improved islet cell survival. Selective inhibitors of cyclooxygenase, such as indomethacin or acetylsalicylic acid, did not improve islet cell survival. Full protection was seen in the presence of NDGA, an inhibitor of lipoxygenase, and partial suppression was caused by BW755c, an inhibitor of both lipoxygenase and cyclooxygenase. We conclude that inflammatory islet cell death caused by activated macrophages involves the activation of arachidonic acid metabolism and of poly(ADP-ribose)polymerase, but that scavenging of oxygen free radicals provides little protection from lysis. PMID- 8348758 TI - Anatomy, histology, and pathology of the cardiac conduction system--Part III. PMID- 8348759 TI - Percutaneous mitral balloon valvotomy in a patient with coexistent mitral stenosis and hypertrophic cardiomyopathy. PMID- 8348757 TI - Surface expression of adenosine deaminase in mitogen-stimulated lymphocytes. AB - Adenosine deaminase (ADA) expression on the surface of mitogen-stimulated lymphocytes was studied by flow cytometry. The gate for lymphocytes was located by cell size (forward scatter), cytoplasmic complexity (side scatter) and by expression of the markers CD2, CD4, CD8 and CD19. After mitogenic proliferation two populations appeared, one corresponding to non-stimulated cells, and the other consisting of larger cells which showed relatively high expression of adenosine deaminase on their surface. The increase was similar to that observed for CD71 expression, and paralleled the increase in 3H-thymidine incorporation. There was a correlation between ADA and CD71 expression (r = 0.92 for phytohaemagglutinin (PHA) and 0.97 for pokeweed mitogen (PWM)). These results suggest a role for ecto-adenosine deaminase in lymphocyte proliferation and/or triggering. PMID- 8348760 TI - Stroke and atrial fibrillation: to anticoagulate or not. AB - After reviewing these published studies, I think one can conclude that in the patient population with chronic and/or paroxysmal atrial fibrillation, warfarin is beneficial and the benefits outweigh the risks. However, it is important to point out that patients at high risk for embolic disease, for example, dilated cardiomyopathy patients, were rarely included in these trials. The five trials mentioned above do not address this patient population. Current opinion is that these individuals should receive anticoagulation despite the lack of objective evidence that anticoagulation is beneficial if the risk of bleeding is not excessive. The five trials also do not address the population of patients categorized as having "lone atrial fibrillation," that is, atrial fibrillation occurring in patients with no structural heart disease. The general consensus in the low embolic risk patient, (i.e., the patient < 60 years of age who has lone atrial fibrillation) is that the risk of anticoagulation is greater than the benefit. My final thought on the subject concerns the risk of pulmonary emboli in this patient population. My guess is that this group of patients is at high risk for small pulmonary emboli, which in many instances may be subclinical--for example, clots too small to result in persistent tachypnea or tachycardia. As far as I can tell, there are no randomized trials on the prevention of pulmonary emboli in patients with chronic or paroxysmal atrial fibrillation using anticoagulation or aspirin. I guess the systemic emboli trial data are sufficient to indicate a protective effect on the lungs as well as on the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348761 TI - The noninvasive assessment of myocardial viability. AB - The major objective of noninvasive imaging for detection of myocardial viability is to assist in the improved selection of patients with coronary artery disease and severe left ventricular dysfunction who would benefit most from revascularization. The techniques most commonly used to identify viable myocardium are thallium-201 (201Tl) scintigraphy, positron emission tomography (PET) using a flow tracer in combination with a metabolic tracer, technetium-99m (99mTc) sestamibi imaging, and dobutamine echocardiography. On stress 201Tl scintigraphy, asynergic regions showing normal thallium uptake, an initial defect with delayed redistribution at 3-4 h, late redistribution at 24 h, or defect reversibility after reinjection of a second dose of 201Tl at rest all suggest preserved viability. The greater the final uptake of 201Tl in areas of regional myocardial dysfunction preoperatively, the greater the improvement in ejection fraction after coronary revascularization. Demonstration of uptake of fluoro-18 deoxyglucose (FDG) in regions of diminished blood flow on PET imaging also correlates well with improved systolic function after revascularization. 99mTc sestamibi may also be useful for assessment of myocardial viability, particularly after thrombolytic therapy for acute myocardial infarction. Dobutamine echocardiography has good positive predictive value for viability determination, but absence of systolic thickening in an akinetic zone in response to intravenous infusion of the drug may still be associated with viable myocardium in 25-50% of segments. Of all the techniques cited above, quantitative resting 201Tl scintigraphy may be the best approach for distinguishing between viable and irreversibly injured myocardium. PMID- 8348762 TI - Comparison between diurnal distribution of onset of infarction in patients with acute myocardial infarction and circadian variation of blood pressure in patients with coronary artery disease. AB - We analyzed the diurnal distribution of the onset of infarction in 636 patients with acute myocardial infarction (MI) and compared it with the circadian variation of blood pressure in 57 patients with coronary artery disease (CAD). In addition, we studied the modification of the circadian blood pressure variation during treatment with antianginal medications in 20 patients with CAD. A marked diurnal periodicity (p < 0.05) was observed for the onset of MI, with peaks seen in the late morning, late evening, and very early morning. The blood pressure in the patients with CAD was elevated in the morning, reduced in the late evening, and was the lowest in the very early morning. The peaks of onset of infarction temporally corresponded to the characteristic feature of blood pressure profile observed in the patients with CAD, that is, the morning rise, the late evening decline, and the very early morning reduction. Antianginal medications significantly reduced the blood pressure, not only during the day (p < 0.02) but also at night (p < 0.05). These observations suggest that the decline in blood pressure, as well as the morning surge in blood pressure, may be closely related to the onset of MI. Therefore, when treating patients with CAD with antianginal medications which can potentially reduce blood pressure, the effects on the circadian variation of blood pressure should be considered. PMID- 8348763 TI - Plasma level changes of fibrinopeptide A after uncomplicated coronary angioplasty. AB - Fibrinopeptide A (FPA) is a small polypeptide cleaved from fibrinogen by thrombin, has a short half-life, and is considered a sensitive biochemical marker of thrombin activity, fibrin generation, and ongoing thrombosis. Increased plasma levels of FPA have been reported in various procoagulable and thrombotic medical and cardiovascular disorders, including acute myocardial infarction, unstable angina, and sudden cardiac death. However, activation of thrombosis by the arterial injury incurred during coronary angioplasty has not been systematically examined with use of plasma FPA measurements. To detect and monitor activation of thrombosis by coronary angioplasty, plasma levels of FPA were obtained by venipuncture and measured by radioimmunoassay before, immediately after, 24 to 48 h later, and 1 and 3 months after uncomplicated coronary angioplasty. From December 1990 through June 1991, FPA was measured in 30 patients (28 men and 2 women, aged 54 +/- 9 years) with coronary artery disease who were undergoing coronary angioplasty. The mean left ventricular ejection fraction was 55 +/- 7%. The dilated vessel was the left anterior descending coronary artery in 20 patients (together with a second vessel in 2), the right coronary artery in 9, and the left circumflex in 1. The procedure was successful and free of major complications in all patients. Before angioplasty the FPA levels averaged 6.50 +/ 1.18 ng/ml. Shortly after angioplasty they rose to 20.20 +/- 7.91 ng/ml (p = 0.08) despite intravenous heparin. At 24 to 48 h and after heparin had been discontinued for at least 4 h, the mean FPA levels were significantly higher (32.33 +/- 10.86 ng/ml) compared with baseline values (p = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348764 TI - Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure. AB - The present study was designed to investigate whether brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations correlate with left ventricular end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP), diastolic pulmonary arterial pressure (DPAP), right atrial pressure (RAP), or ejection fraction (EF). Plasma BNP and ANP levels were determined by commercial radioimmunoassays (Peninsula) after Sep Pak C18 extraction in blood samples withdrawn from the pulmonary artery and the left ventricle or from the left ventricle and the femoral vein in 85 patients undergoing diagnostic cardiac catheterization. Linear and nonlinear regression analysis and the paired sample t-test were applied to the data. Pulmonary arterial plasma BNP and ANP levels showed a close nonlinear correlation with LVEDP (BNP: r = 0.94, p < 0.001; ANP: r = 0.81, p < 0.001), a significant linear correlation with PCWP, DPAP, and RAP, and a significant negative correlation with EF. ANP concentrations decreased significantly from the pulmonary artery to the left ventricle and from the left ventricle to the femoral vein (p < 0.001). BNP levels also decreased significantly between the left ventricle and the femoral vein (p < 0.001), but there was no significant difference between pulmonary arterial and left ventricular BNP concentrations. BNP and ANP concentrations correlated significantly between pulmonary arterial and left ventricular blood samples (BNP: r = 0.99, ANP: r = 0.93, p < 0.001) and between left ventricular and peripheral blood samples (BNP: r = 0.99, ANP: r = 0.94, p < 0.001). The present data suggest that peripheral plasma BNP and ANP levels are useful non invasive indices of cardiac performance. PMID- 8348765 TI - Prognosis in diabetics in whom the initial suspicion of acute myocardial infarction was not confirmed. AB - For 2,058 consecutive patients hospitalized for suspected acute myocardial infarction (AMI) but in whom AMI was later ruled out, we describe the prognosis with particular emphasis on diabetics. In all, a previous history of diabetes mellitus occurred in 290 (14%) of the patients. Compared with nondiabetics, they had a longer delay time between onset of symptoms and arrival in hospital. During 1 year of follow-up, their mortality rate was 28% compared with 14% for nondiabetics (p < 0.001), and their reinfarction rate was 20% compared with 10% for nondiabetics. More diabetics died in association with a fatal myocardial infarction and more frequently had ventricular fibrillation preceding death. With the exception of reinfarction, no clear difference in terms of morbidity was observed between the two groups. We conclude that the prognosis in diabetics in whom AMI is ruled out is poor, with between one-quarter and one-third not surviving 1 year. PMID- 8348766 TI - Anatomy, histology, and pathology of the cardiac conduction system--Part V. AB - Although morphologic findings in many of the cardiac arrhythmias of acute and chronic disease have been elusive, the correlates of heart block (particularly atrioventricular block) are abundant. Pathologic features of sinoatrial, atrioventricular, and bundle-branch block are reviewed. Lev and Lenegre diseases (idiopathic bilateral bundle-branch fibrosis) are also reviewed. PMID- 8348767 TI - Anomalous inferior vena cava mimicking aortic dissection on transesophageal echocardiography. AB - Transesophageal echocardiography (TEE) is considered an excellent method for the diagnosis of aortic dissection, especially that involving the descending aorta. It has also proved useful in the evaluation of conditions mimicking aortic dissection, usually disclosing in these situations other types of severe aortic disease. We are not aware of any report dealing with venous abnormalities which presented diagnostic problems in a patient evaluated with TEE because of a suspected aortic dissection. PMID- 8348768 TI - Late rupture of left ventricular true aneurysm after acute myocardial infarction. AB - Left ventricular (LV) free wall rupture complicated with acute myocardial infarction (AMI) usually occurs in the early phase of AMI. True aneurysm of the LV is sometimes a complication of AMI but rarely ruptures. In our patient, a 72 year-old woman, the LV free wall ruptured on Day 49 after the onset of AMI and the ruptured site was the thinnest wall of large true aneurysm of the LV. The large aneurysmal formation probably was due to corticosteroids used for pericarditis. More attention should be paid to late cardiac rupture and the use of corticosteroids. PMID- 8348769 TI - Richard Gorlin. PMID- 8348770 TI - Neuroscience of HIV infection: basic and clinical frontiers 1993. Vienna, June 2 5, 1993. Abstracts. PMID- 8348771 TI - 29th annual meeting of the Italian Neuropathological Association. Verona, June 17 19, 1993. Abstracts. PMID- 8348773 TI - Simultaneous analysis of cell surface antigens and DNA content by flow cytometry. AB - Cells obtained from the blood or bone marrow of patients with haematological malignancies can both be stained with fluorescent labelled monoclonal antibodies to determine an immunophenotype and permeabilized with 30% ethanol then stained with propidium iodide for simultaneous DNA analysis. In the technique described here, no evidence of selective depletion of the malignant cell population was demonstrated and decreases in the mean fluorescence intensity of the surface markers were insufficient to affect the sensitivity of flow cytometric analysis. The combined method is simple and robust enough to allow incorporation of DNA analysis into routine immunophenotyping of leukaemia and lymphoma cells. PMID- 8348774 TI - Use of a low pressure liquid chromatography system for haemoglobinopathy screening. AB - A closed low pressure liquid chromatography system (LPLC) is described which is suitable for haemoglobinopathy screening. The system (Glycomat) was originally developed for the quantitation of the glycated haemoglobin (HbA1). The same biochemical principles have been applied to the separation of haemoglobin A2 (HbA2) and haemoglobin variants. The instrument offers three modes of use including a fast haemoglobin elution, a variant screen and a HbA2 assay for thalassaemia screening. The fast screen isolates all of the common haemoglobin variants except HbE which elutes with HbA. This mode is a more rapid alternative to the Sickledex test. The variant screen produces a wider separation of abnormal variants giving an identification and quantitation for each. The HbA2 assay separates this minor fraction from all other haemoglobins giving an accurate percentage. Abnormal variants are also separated. To validate the HbA2 assay 252 samples were assayed by the cellulose acetate electrophoresis/elution method and LPLC with a correlation of 0.932. The system provides an accurate and sensitive alternative to traditional manual chromatography and electrophoresis methods. The automated sampler allows batches from 1-99 samples to be processed with significant savings in operator time. PMID- 8348775 TI - Bone marrow fibrosis: histomorphometric analysis and interobserver reproducibility of a simple optical method of assessing its intensity. AB - A histomorphometric analysis of the length of reticulin fibres per area of haemopoietic bone marrow was performed on 59 trephine iliac crest biopsies. The values obtained were found to correlate with the degree of fibrosis as determined by a simple optical method based on the degree of microscopic magnification required for recognition of the presence of reticulin fibres. The mean length of fibre (microns/10,000 micron2) for the three degrees of fibrosis defined by the optical method were: 241.8 +/- 16.6 for grade I, 713 +/- 85.6 for grade II, and 1827.9 +/- 230.4 for grade III (P < 0.001). In a series of 67 biopsies, the overall interobserver agreement of the optical method was found to be good (Spearman's r = 0.99; P < 0.001) and there was good individual agreement for each of the three degrees of fibrosis (improved kappa test). There was a small amount of overlap between the extreme values of adjacent optical degrees. These results suggest that the optical method described here can be recommended as a practical technique for the routine evaluation of myelofibrosis. PMID- 8348772 TI - Comparative evaluation of three flow cytometers for reticulocyte enumeration. AB - Flow cytometric determination of reticulocytosis is progressively replacing the manual microscopic method. We evaluated three flow cytometers (Becton Dickinson FACScan, Coulter EPICS Profile II, Ortho Cytoron Absolute) for reticulocyte enumeration, using thiazole orange. For each sample, 30,000 cells were analysed. In order to comparatively evaluate the three instruments, reticulocytes were counted by manually gating the erythroid population and evaluating the gated population for fluorescence characteristics. The different instruments showed good linearity and precision. No carry-over was observed. Orthogonal regression analysis of reticulocyte counts of 100 healthy blood donor samples and 108 haematological patient samples showed a good mutual comparability between all three instruments tested, although the paired t-test showed a significant difference between the Cytoron and both the FACScan and the Profile. Despite minor statistical differences, the three instruments can be considered equivalent for daily routine reticulocyte enumeration. PMID- 8348776 TI - Infectious mononucleosis complicated by haemolytic anaemia due to the Donath Landsteiner antibody and by severe neutropenia. AB - A young man developed infectious mononucleosis complicated by profound anaemia due to haemolysis. The Donath Landsteiner antibody was found in his serum. He was treated successfully by blood transfusion but subsequently developed severe neutropenia. Both complications have been reported previously but not in the same individual. No underlying immune deficiency could be identified. PMID- 8348777 TI - Multiple fungal infection in acute lymphoblastic leukaemia. PMID- 8348778 TI - Platelet cross matching. PMID- 8348779 TI - Severe thrombocytopenia in tuberculosis. PMID- 8348780 TI - Suppression of erythroid progenitor cells during malarial infection in Thai adults caused by serum inhibitor. AB - The bone marrows of 21 Thai adults infected with Plasmodium falciparum malaria were cultured for CFU-E and BFU-E by using AB serum, autologous serum (parasitaemia) and autologous serum (post-parasitaemia). Six patients had no complication and 15 patients had pulmonary, renal or haematologic complications. In the non-complicated cases, sera during parasitaemia did not suppress the post parasitaemia CFU-E and BFU-E. Post parasitaemia, there was suppression of CFU-E by parasitaemia sera. In the complicated cases, the autologous sera during parasitaemia suppressed the growth of both CFU-E and BFU-E both during and after parasitaemia (P < 0.05). The post-parasitaemia sera had neither a suppressive nor a stimulating effect. In the complicated cases, the progenitor cells cultured from the bone marrow post-parasitaemia were fewer in number than those cultured from the bone marrow during parasitaemia using the same sera. Two possible mechanisms of suppression are postulated, namely the reduction of erythropoietin or the increased tumour necrosis factor during malarial infection. Further studies to clarify this are being carried out. PMID- 8348781 TI - Alcohol induced burr cell (echinocytic) haemolytic anaemia and haemochromatosis. AB - A 51-year-old man with chronic alcoholic liver disease developed a severe haemolytic anaemia characterized by the presence of circulating burr-shaped cells (echinocytes). Several transfusions of packed red cells were ineffective in raising the haemoglobin concentration, showing that the abnormality was acquired by the transfused cells. Liver biopsies revealed haemochromatosis. Haematological parameters normalized four months after the patient stopped drinking alcohol, but burr cells were still present and erythrocyte life-span was still markedly shortened at one year follow-up. Since serum cholesterol, HDL-cholesterol, and Apo-AI and Apo-B lipoproteins were considerably decreased, the lipid composition of the red cell membrane was studied. Findings showed that echinocytosis occurred with no change in membrane cholesterol content, nor in cholesterol:phospholipid ratio, but with an alteration in the phosphatidylserine and phosphatidylinositol concentrations. While haemochromatosis was most likely the cause of the erythrocyte anomaly, alcohol intake was probably responsible for the acute onset of haemolytic anaemia with effects directly on the erythrocyte membrane as well as mediated by the progressive hepatic injury, with alterations in the plasma and successively in the intramembrane lipid composition. PMID- 8348782 TI - Should the drinking water of Truro, Nova Scotia, be fluoridated? Water fluoridation in the 1990s. AB - An epidemiological assessment of differences in caries and fluorosis prevalences between children in Truro (< 0.1 ppm) and Kentville (fluoridated at 1.1 ppm in 1991), Nova Scotia, Canada, was completed in 1991. Out of a total of 429 children, in grades 5 and 6, in the two towns in 1991, 219 (51%) were examined. Parents answered a self-administered questionnaire investigating the sources of drinking water used by the children since birth, residence history, use of fluoride supplements, dentifrices, and other fluoride products during the first 6 yr of the life. The examination criteria differentiated between non-cavitated and cavitated carious lesions. Dental fluorosis was measured using the TSIF index. Examiner agreement was excellent. Of the children examined, 80 (36.5%) drank water (fluoridated or non-fluoridated) from municipal water systems during the first 6 yr of life. The children were assigned into five groups based upon residence history and exposure to fluoridated water during the first 6 yr of life. The percentage difference in mean DMFS scores between children in the fluoridated and non-fluoridated groups is 17% (delta DMFS1 = 0.7) when non cavitated carious lesions are included and 39% (delta DMFS2 = 1.1) when they are excluded. The differences are not statistically significant. The significant risk factors associated with the DMFS1 and DMFS2 scores identified by a stepwise multiple regression analysis are: education level of the father, gender, and number of years of reported use of toothpaste during the first 6 yr of life. Dental fluorosis (mainly TSIF score of 1) was present in 41.5% and 69.2% of the children in the non-fluoridated and fluoridated groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348783 TI - Association between untreated caries and age, gender and dental attendance in adults. AB - The aim of the study was to examine the association between untreated caries on the crown and root of the tooth with the age, gender and dental attendance in a group of adult. Six general practitioners in the Greater Manchester area agreed to take part. Over a 6-week period they collected clinical and personal data on 270 of their adult patients. No association was found between the mean number of coronal surfaces with caries and age; however, there was more root caries in people over 55 yr. More recurrent caries associated with a restoration was diagnosed than primary caries. There were proportionally more female than male regular attenders, and once attendance has been taken into account there were no gender differences for either coronal or root caries. Both coronal and root caries were associated with attendance, with irregular attenders experiencing more. Irregular attenders were three and a half times more likely to have caries on the root surfaces than regular attenders. PMID- 8348784 TI - Perceived need and use of oral health services among adolescents and adults in Tanzania. AB - The perceived need and use of oral health services among adolescents and adults in Tanzania were studied. One region from each of the country's five zones was chosen at random. Final sample selection (n = 1061) was done in the main towns of the selected regions. Participants were interviewed using a structured questionnaire which dealt with perceived need for dental treatment and use of oral health services and several demographic variables. Frequency tables were computed and analyzed. Odds ratios were calculated based on 2 x 2 tables and logistic regression models. The majority, 82% (95% CI: 79-85%) had sought treatment due to pain or for tooth extraction. Perceived need, dissatisfaction with own oral health status and use of oral health services were slightly more frequent among women. Bleeding gums had no explanatory value on the dependent variables. The strongest explanatory variable in a logistic regression model for perceived need and dissatisfaction with own oral health status was previous dental treatment with an estimated odds ratio of 6.4 (95% CI: 4.7-8.7) and 7.2 (95% CI: 5.3-9.9), respectively. People living nearest a treatment facility tended to use the services more [odds ratio 1.3 (95% CI: 0.8-2.1)]. A very strong relation between previous dental problems and use of oral health services was found, namely an odds ratio of 68.8 (95% CI: 39.0-121.4). The findings in the study may be useful in the attempts to implement Tanzania's National Plan for Oral Health. PMID- 8348786 TI - Transmission of mutans streptococci to infants following short term application of an iodine-NaF solution to mothers' dentition. AB - In a randomized clinical trial, six applications of an I2-NaF or a placebo solution were administered to the mothers' dentition at the time of tooth emergence of her infant, to evaluate its effect on transmission of mutans streptococci (MS) to the infant. MS and other bacterial levels were periodically monitored in 48 mother-infant pairs until the child's third birthday. There were significant reductions in maternal salivary MS (P = 0.04), lactobacilli (P = 0.04), total streptococci (P = 0.002), and total cultivable organisms (P = 0.004) immediately following treatment. In children, 3-yr incidence of MS colonization and the time of acquisition of MS or the caries experience did not differ significantly between the two groups. We conclude that short-term application of I2-NaF to the maternal dentition of predentate infants significantly lowers MS, lactobacilli, total streptococci, and total cultivable bacteria in mothers' saliva, but does not influence the incidence and the time of acquisition of MS or the caries experience in children. PMID- 8348785 TI - Use of health care services in two rural communities in Tanzania. AB - This study was undertaken to investigate the pattern of utilization of medical and dental health care services in rural Tanzania. Two hundred adults, 91 men and 109 women aged 20 or over, were interviewed. Nearly all subjects reported using modern dental and medical health care services. Home remedy was the only indigenous method of treatment used for dental problems while for medical problems a traditional healer was the most commonly used indigenous alternative. The use of both indigenous and modern health care services was significantly lower for dental than for medical problems (P < 0.05). It seems that the pattern of utilization of health care services differs for medical and dental problems. This should be taken into account when planning comprehensive health care services for rural African societies. PMID- 8348787 TI - Simplified preventive dentistry program for Chilean refugees: effectiveness of one versus two instructional sessions. AB - A simplified dental health program for newly arrived refugees was evaluated. The efficacy of presenting the program in one instructional session or two was compared. 193 Chilean refugees, granted residency in Stockholm in Spring 1981 or in Spring 1982, participated. The subjects were divided into two groups. One group received a dental health program only at the first visit, in conjunction with the baseline examination, and the other group was recalled for a further session 3 months after the baseline examination. Both groups were recalled for evaluation 6 months after the initial visit. At follow-up the groups comprised 94 and 65 subjects respectively. The mean relative reductions in gingivitis (relating GBI reduction to baseline GBI) were 33.2% (95% < I: 29.1 to 37.3%) in the single-visit group and 40.5% (95% < I: 35.9 to 45.8%) in the two-visit group. The reduction in periodontal pocket depth was mainly a reduction of shallow pockets. The maximum effect was attained after one instructional session. PMID- 8348789 TI - Concern for dental appearance among Norwegian young adults in region with low uptake of orthodontic treatment. AB - The purpose of the present study was to examine orthodontic concern among orthodontically untreated young adults living in an area where the relative number of children receiving treatment was only 15-20% and to compare orthodontic concern among these individuals with that of untreated persons from an area with a higher treatment frequency. All the subjects were clinically examined and impressions for dental study casts, radiographs and photographs were taken. The subject's occlusion was classified according to two methods: 1) allocation to one of four groups according to the national Need for Orthodontic Treatment Index (NOTI), and 2) allocation to one of three groups according to presence or absence of six Anterior Occlusal Traits (AOT). Frequencies of NOTI scores demonstrated that in the study group more individuals were in need of treatment relative to the comparison group. Reported concern was at the same level in both groups, and significantly related to NOTI and AOT scores. The individuals in the area with the low treatment frequency were generally less aware of their anterior traits compared to the individuals in the area with a higher treatment frequency. The results indicated that a long-term low uptake of orthodontic treatment among children in the particular area was not accompanied by a similar increase in concern about own dental appearance in early adulthood. PMID- 8348788 TI - Cross validation of a Brazilian version of the Dental Fear Survey. AB - The Dental Fear Survey (DFS), a paper and pencil instrument for assessing dental fear and avoidance, has been widely used and validated in fear studies in the US. However, before such instruments are used in countries and cultures dissimilar to the one in which it was developed, they should be cross-validated in that culture. The present study is an examination of the DFS response characteristics in a group of 374 Brazilian university students. Factor analysis of the DFS revealed three factors essentially identical to those found among university students in the US and in Singapore, as well as among US adult dental patients. Higher DFS scores were significantly associated longer intervals since last dental visit. These results are taken as evidence that the DFS performs in this Brazilian sample very much as it does in other samples; and is thus, a valid indicator of dental fear at least among Brazilian university students. PMID- 8348791 TI - Congenitally missing permanent mandibular incisors and their association with missing primary teeth in the southern Chinese (Hong Kong). AB - A radiographic survey of a random sample of 454 girls aged 5.9 +/- 0.5 yr and 521 boys aged 5.8 +/- 0.4 y was undertaken to establish data on the incidence of congenitally missing mandibular incisor teeth amongst the Southern Chinese and to compare these figures with those of a similar previous study of 12-yr-olds so to eliminate factors such a trauma or extractions which may have artificially inflated the 12-yr-old incidence data. The proportion of 5-yr-old girls and boys affected by hypodontia in the permanent mandibular incisor region was 0.086 and 0.046 respectively (a significant difference between sexes, P < 0.02), compared with 0.047 and 0.034 for the 12-yr-olds (a non-significant difference) so other factors must have contributed to the discrepancy between the two groups of children. A very strong correlation (P < 10(-25)) between missing primary and missing permanent mandibular incisors is present in this group, and this has implications for prognosis and treatment planning. A fundamental developmental defect is implied. PMID- 8348790 TI - Gingival and periodontal health in systemic lupus erythematosus. AB - This study compared the periodontal health of patients with SLE with that of healthy controls. Patients with systemic lupus erythematosus had significantly lower periodontal probing depths compared with healthy controls. It is possible that systemic drugs such as corticosteroids and NSAIDS may be responsible for these reduced probing depths but this study did not reveal a statistically significant effect of drugs. There is thus no evidence for a predisposition to increased periodontal disease in SLE. PMID- 8348792 TI - Subjective reports of oral dryness in an older adult population. AB - In this study of an older adult population almost one-fifth reported oral dryness. It was the most common of 22 oral symptoms and complaints. In a logistic regression analysis of predictors of oral dryness three variables had significant independent effects: income, taking prescribed medications and experiencing a stressful life change within the previous 6 months. Subjects with oral dryness had more decayed crown surfaces than those without but there was no association with decayed root surfaces. Nor were there any significant associations between reports of oral dryness and a number of indicators of periodontal health. Those with dryness were more likely to report other oral symptoms such as unpleasant taste, a burning sensation in the tongue and other parts of the mouth and pain from dentures. They were also more likely to report problems chewing food, problems with eating and communication and were more likely to be dissatisfied with their oral health. Given its prevalence and effects, oral dryness constitutes an important health issue among older adults. PMID- 8348793 TI - Oral health and treatment needs among patients in psychiatric institutions for the elderly. AB - The purpose of the study was to assess oral health and treatment needs among elderly in psychiatric institutions in a Danish county. The study serves as baseline for the evaluation of a newly established oral health care program in the county. The study population comprised the residents in eight institutions (n = 407). Two thirds of the residents were edentulous, 34% of the dentate had one or more root remnants, and 55% had untreated decay. The dentate with regular dental visiting habits had significantly less untreated decay than the irregular users. The oral hygiene was poor, but was not related to whether or not the elderly were assisted in daily oral hygiene. The evaluation of the program will show to what extent treatment takes place, and whether or not oral hygiene improves. PMID- 8348794 TI - Tooth loss and dental caries in an adult population in Navarra, Spain. PMID- 8348796 TI - Stress measures as predictors of periodontal disease--a preliminary communication. PMID- 8348795 TI - Dental caries and prevalence of mutans streptococci in a group of Cambodian children. PMID- 8348797 TI - The referee process. PMID- 8348798 TI - Phenomenology and psychopathology: was there ever a relationship? AB - The philosophical doctrine known as phenomenology is believed by many to have provided during the early 20th century the conceptual basis of the new descriptive language of psychiatry, the very language that made possible the development of systems such as the DSM-III-R. To ascertain whether this is in fact the case is essential to the solution of technical problems affecting current psychopathological descriptions. This report argues against the above mentioned belief, and suggests that the alliance between phenomenology and descriptive psychopathology was just a marriage of convenience, and that it was Karl Jaspers who made it appear as if his own views were based on Husserlian phenomenology. Indeed, a comparison of the clinical meaning and usage of mental symptoms before and after 1913 shows that Jaspers borrowed a great deal from 19th century alienists, and that calling his views phenomenological added little to their meaning. PMID- 8348799 TI - Alogia, attentional impairment, and inappropriate affect: their status in the dimensions of schizophrenia. AB - Previous factor analyses have shown that at least three factors are needed to encompass the positive and negative symptoms of schizophrenia. Despite marked similarities across studies, it remains unclear whether certain symptoms such as alogia, attentional impairment, and inappropriate affect are more closely related to negative or positive symptoms. An exploratory analysis was undertaken of the separate items on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) that constitute the global rating of alogia, as well as the global ratings of attentional impairment and inappropriate affect in 90 schizophrenic patients. Findings indicate that inappropriate affect loads significantly with bizarre behavior and positive formal thought disorder on a disorganization factor, whereas attentional impairment loads significantly on psychotic, disorganization, and negative symptom factors. The global rating of alogia appears to comprise both positive and negative symptoms, with the item poverty of content of speech loading on the disorganization factor, and other items such as poverty of speech, blocking, and increased latency loading on the negative symptom factor. It is concluded that three dimensions are needed to characterize the symptoms of schizophrenia as measured by the SAPS/SANS. The use of three dimensions may be a robust way to further explore the relationship between signs and symptoms and their underlying mechanisms in schizophrenia. PMID- 8348800 TI - The relationship between DSM-III personality disorders and the five-factor model of personality. AB - Two hundred twenty-four first-degree relatives of patients with psychotic disorders were administered the Structured Interview for DSM-III Personality Disorders (SIDP) and completed a self-report instrument to assess dimensions of the five-factor model of personality. All of the DSM-III personality disorders were related to one or more dimensions of the five personality factors; however, the correlations were generally low. It seems that the five personality factors describe important features of DSM-III personality disorders, but are not sufficient to completely explain their characteristics. Future use of the five factor model in conjunction with personality disorder diagnoses may provide useful information for clinical work and research purposes. PMID- 8348801 TI - Attribution of antisocial symptoms in coexistent antisocial personality disorder and substance abuse. AB - Two methods for diagnosing antisocial personality disorder (ASPD) were compared based on whether antisocial symptoms that occurred when subjects also experienced alcohol- or other drug-related problems were counted toward the diagnosis of ASPD. From a family study of alcoholism and ASPD, 93 male subjects who met ASPD criteria in the absence of substance-related problems were contrasted with 312 subjects who were diagnosed with ASPD regardless of whether criterion symptoms occurred along with substance-related problems. Subjects did not differ in types of antisocial behaviors, age of onset of behaviors, or comorbid psychiatric disorders except for alcoholism and drug abuse. A subgroup was contrasted on family history of psychiatric illness, with no differences noted between groups. Counting antisocial symptoms toward the diagnosis of ASPD regardless of whether symptoms occur during periods of substance abuse increases the observed population prevalence of the disorder, but does not change the observed phenomenology of ASPD or affect commonly accepted indicators of validity of diagnosis. PMID- 8348802 TI - DSM-III personality disorders in generalized anxiety, panic/agoraphobia, and obsessive-compulsive disorders. AB - In an earlier report, we stated that personality profiles of patients with panic disorder/agoraphobia (n = 187) and obsessive-compulsive disorder ([ODC] n = 51) were similar, albeit more pronounced in OCD, suggesting that the link between panic disorder/agoraphobia and DSM-III personality disorders (PDs) or traits may be nonspecific. The present report extends the comparative study of DSM-III PDs/traits, as assessed by the Personality Diagnostic Questionnaire (PDQ), by adding a third diagnostic group of 39 patients with generalized anxiety disorder (GAD). The personality assessment of panic disorder/agoraphobia and GAD patients yielded virtually identical results on the PDQ and Eysenck Personality Inventory (EPI). Because GAD lacks the prominent panic, phobic, and obsessive-compulsive symptoms of other anxiety disorders, the present findings provide strong support for a nonspecific link between panic disorder/agoraphobia and DSM-III PDs/traits and for the presence of common personality characteristics in anxiety disorders. PMID- 8348803 TI - Psychometric validation of the Tridimensional Personality Questionnaire: application to subgroups of eating disorders. AB - Eating disorder patients show extremes of the personality characteristics measured by the Tridimensional Personality Questionnaire (TPQ). For this reason, the TPQ was tested in four subgroups of eating disorder patients. Patients completed the TPQ and their responses were compared with a normative sample of women. Results indicated that the TPQ is an internally consistent and valid instrument to use with eating disorder patients. PMID- 8348804 TI - Association between borderline personality structure and history of childhood abuse in adult volunteers. AB - Childhood abuse has been implicated as a leading factor in the development of borderline personality disorder (BPD). Data in this report, drawn from an ongoing study of the therapeutic effect of fluoxetine in BPD patients, were gathered in an attempt to replicate previous findings indicating a history of physical abuse in 71% and sexual abuse in 67% of adult BPD subjects. Thirty-one subjects for a study of the pharmacological treatment of BPD or BPD traits met criteria for the study. Those who had been previously hospitalized for a psychiatric disorder, who had recently been suicidal, or who had recent histories of self-mutilation were excluded. Specific information about childhood abuse was gathered using questions from a previous study of abuse histories in BPD patients. All subjects were then interviewed in greater depth regarding past experiences of abuse as part of the ongoing study of the relationship of childhood attachment experience and adult psychopathology. Six of 31 subjects (19.4%) reported a definite history of childhood physical and/or sexual abuse. Four of these subjects met criteria for full BPD, and two met criteria for BPD traits. Three of 31 subjects reported a history of physical abuse (9.7%); five reported a history of sexual abuse (16.1%). Two of the six who reported abuse reported both physical and sexual abuse. A history of childhood abuse is not necessarily linked to the development of BPD or BPD traits in all individuals. The following hypothesis is suggested: BPD may represent a spectrum of symptomatic severity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348805 TI - Correlates of dissociative symptomatology in patients with physical and sexual abuse histories. AB - Recent studies have demonstrated a high prevalence of sexual and physical abuse histories and high levels of dissociative symptoms in psychiatric inpatients. We examined whether severity, frequency, and age of onset of abuse correlated with subjects' levels of dissociative symptoms. Sixty-four women reporting a lifetime history of physical and/or sexual abuse were recruited from consecutive admissions to three wards of a psychiatric hospital. Subjects completed the Life Experiences Questionnaire (LEQ) and the Dissociative Experiences Scale (DES). Subjects' self-reports of severity, frequency, and age of onset of abuse were analyzed for correlations with DES score. More invasive sexual abuse was associated with more dissociation. Higher-frequency physical abuse was associated with more dissociation, but no conclusion could be drawn about the impact of frequent sexual abuse due to missing data. An inverse correlation was found between age of onset of abuse and degree of dissociative symptomatology. These preliminary findings are consistent with hypotheses linking more severe, more chronic, and earlier abuse to the greater development of dissociative symptoms. The findings further emphasize the importance of recognizing dissociative symptoms in the clinical setting, and of continued study into the effects of childhood trauma. PMID- 8348806 TI - Karen Horney's "resigned person" heralds DSM-III-R's borderline personality disorder. AB - It is shown here that what Karen Horney called the resignation solution to the problem of basic anxiety leads to psychopathology very similar to DSM-III-R's borderline personality disorder (BPD). Both the "resigned person" and the borderline personality show instability of self-image, social relationships, and mood, and live out the associated deficits with similar styles. While not specifically using the term "splitting", Horney showed how alternating expansive and self-effacing trends can coexist in the resigned person, and how these oscillations in self-other-world constitution influence the resigned person's behavior in a way similar to borderline splitting. Horney's descriptive and psychodynamic analysis of the resignation phenomenon elaborates and gives additional credibility to DSM-III-R's BPD as a diagnostic category. PMID- 8348807 TI - Reliability and validity of the Japanese version of the Tridimensional Personality Questionnaire among university students. AB - The Tridimensional Personality Questionnaire (TPQ) is a self-rating questionnaire, based on a general biosocial theory, for the clinical description and classification of both normal and abnormal personality variants. It was translated into Japanese and administered with the General Health Questionnaire (GHQ) and the 10-item version of the Social Desirability Scale (SDS) to 450 university students on two occasions 2 months apart. Pearson Product-Moment Correlation Coefficients and kappa-coefficients between TPQ scale scores for the two occasions were significantly high, as were Cronbach's alpha-coefficients of TPQ scales and subcategories at the first wave. Correlations between the TPQ scale score and GHQ and SDS scores were negligible. The TPQ thus appears to have test-retest reliability and content validity among a Japanese student population; it is uninfluenced by psychiatric morbidity or social desirability. PMID- 8348808 TI - Grading depression severity by symptom scores: is it a valid method for subclassifying depressive disorders? AB - Recent diagnostic criteria such as the DSM-III-R and the 10th Revision of the International Classification of Diseases (ICD-10) have proposed that depression should be subcategorized according to severity. Among 75 inpatients with Research Diagnostic Criteria (RDC) major depressive disorder, the total number of criterion B items (N = 8) used as the measure of severity was validated against the global assessment scale (GAS) score for the worst week of the episode; the correlation between the two was r = -.232. This suggests that even if the total number of identified diagnostic items reflects a different aspect of severity, there should be caution about its use unless validated by further study. PMID- 8348809 TI - [The computer in journal preparation. Desktop publishing]. PMID- 8348810 TI - [Prophylactic administration of anticoagulant therapy in electric cardioversion for atrial fibrillation or atrial flutter]. PMID- 8348811 TI - [Vaclav Libensky. 7 June 1877, Prague--30 December 1938, Prague. Vaclav Libensky and his contribution to Czech cardiology]. PMID- 8348812 TI - [Ischemic disease of the lower extremities (continued)]. PMID- 8348813 TI - [Transesophageal echocardiography]. PMID- 8348814 TI - Do preoperative branched-chain amino acids have a beneficial effect on the heart after cardiac surgery? AB - To verify the hypothesis, formulated on the basis of data emerging from animal experiments, that branched-chain amino acids (BCAA) exert a protective effect on the heart during ischaemia, eight patients immediately before aortocoronary reconstruction were provided 400 ml of a 3% BCAA solution. A control group comprised another eight patients. Per- and postoperative myocardial status and myocardial enzyme levels were assessed. Myocardial biopsy was performed during surgery to determine glycogen levels. Creatine kinase (CK) levels were invariably higher in the BCAA group, with statistically significant differences in samples obtained immediately after surgery (10.6 +/- 3.35 mu kat/l vs. 4.07 +/- 0.59, p < 0.0004), in the evening after surgery (14.2 +/- 5.92 vs. 5.91 +/- 2.21, p < 0.06) and in the morning of the first postoperative day (18.0 +/- 10.1 vs. 7.5 +/- 4.76, p < 0.025) when aspartate aminotransferase (AST) levels were likewise higher (1.35 +/- 0.28 vs. 1.00 +/- 0.26, p < 0.035). There were no differences between the groups in the number of defibrillations after ischaemia, myocardial glycogen content, peroperative ischaemia, incidence of arrhythmia and catecholamine support. We conclude that BCAA at the above indicated doses did not raise myocardial glycogen content or improve myocardial status after cardiac surgery. Their administration resulted in a rise in CK and AST in the postoperative period. PMID- 8348815 TI - The course of myocardial hypertrophy in hypertrophic cardiomyopathy. Results of a 10-year follow-up. AB - Sixty-nine patients with hypertrophic cardiomyopathy were followed up for a minimum period of 10 years, with detailed quantitation of myocardial hypertrophy using two-dimensional echocardiography at a two-year interval. The parameters determined included maximum myocardial wall thickness, mean myocardial wall thickness (defined as the arithmetic mean of myocardial wall thickness values measured in ten areas of approximately the same size the LV and septal myocardium had been divided into), and the extent of hypertrophy (percentage of the myocardium affected by hypertrophy). Other echocardiographic parameters as well as clinical, ECG and Holter data were also assessed. Seven patients (10%) showed a gradual increase in mean myocardial wall thickness (associated with an increase in maximum myocardial wall thickness and in the extent of hypertrophy in two). By contrast, a progressive decrease in hypertrophy was observed in six patients (9%). In either case, the observed changes tended to involve areas in segments outside the zone of maximum wall thickness. Generally, the changes in hypertrophy were not related to the development of clinical or Holter manifestations, and were unaffected by verapamil or beta-blocker therapy. There was no death among these patients unlike the five deaths in a group with stationary hypertrophy. Based on their results, the authors conclude that changes in myocardial hypertrophy (regardless of whether there is progression or regression) probably make part of natural variations in the course of the disease, and have no clinical or prognostic implications for the majority of patients. PMID- 8348816 TI - [Preventive cardiology in the Czech Republic. Present status and perspectives]. AB - Despite their proclaimed goals, prevention campaigns were little effective in the past. Now it is time to discard those highly publicized programmes. Preventive cardiology can be successful in reducing the incidence and mortality only on condition the endeavor of the public health system is combined with a well functioning service of general practitioners and family physicians. The nationwide model of prevention should be translated into practice by institutes of public health and hygiene and should improve, mainly by redefining the dietary habits and smoking cessation programmes, the risk profile of the entire population. It should be remembered that even a minor change in the risk profile in the whole population has society-wide implications and entails a significant decrease in the number of clinically manifest cases of the disease. While secondary prevention after myocardial infarction will continue to be the responsibility of the cardiologist, individualized intervention in persons at high risk, as part of primary prevention, can be provided generally only on condition it is performed by the general practitioner and the family physician. All multi-level models designed to refer patients and persons at risk step by step, according to the degree of risk, up the health system, as proposed by socialist health care, are not practicable. Today, the general practitioner can consult the expert directly should the need arise. Successful prevention will depend on the standard and education of the general practitioner on the one hand, and the performance of public health institutions on the other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348817 TI - [The Williams syndrome in adulthood]. AB - A case report of a 45-year-old woman with Williams syndrome who was indicated, because of increasing problems, for surgery of a supravalvular stenosis of the ascending aorta. In addition to lesions on the aorta, examination revealed multiple stenoses of branches of the pulmonary artery. The patient showed no facial changes or signs of mental retardation. The operation was performed in extracorporeal circulation by suturing a Dacron flap into the stenotic segment of the aorta, and reimplantation and reconstruction of the stenosed aortic arch branches. The procedure was uneventful and, four months after surgery, the patient is completely free of problems. PMID- 8348818 TI - The Victoria Declaration. PMID- 8348819 TI - Accelerated cholesterol synthesis in the monocytes of young myocardial infarction survivors. AB - The substantial role of monocytes in atherogenesis has been demonstrated recently. The feedback regulation of endogenous cholesterol synthesis in monocytes of young myocardial infarction survivors was determined and compared to that of age- and sex-matched controls. The cholesterol synthesis in monocytes of one half of patients was three times higher compared to that of controls whereas the other half showed a rate within the range of controls. PMID- 8348820 TI - The fuzzy boundaries of apperceptive agnosia. AB - Following a trauma that mainly involved the right hemisphere, a 21-year-old girl showed a profound impairment in visual object recognition, without language and intellectual deficit. Her elementary sensory functions were preserved and she performed in the normal range on visual matching tasks, on taks requiring to detect small differences between similar complex shapes and in copying drawings, without any evidence of a line by line approach. Her deficit emerged with tests that, though not implying identification of meaning, demanded to disentangle a form from a confused background and to achieve a highly structured description of the stimulus. In addition to this high-level perceptual processing disorder, there was a deficit in recovering from the visual store the shape of an object, also when the performance did not involve perceptual discrimination, e.g., in drawing from memory or telling the physical difference between two named stimuli. Knowledge of the semantic and contextual attributes of objects was intact. The case is taken as evidence that the borders of apperceptive agnosia may be ampler than usually thought and its distinction from associative agnosia less rigid, with some patients laying in-between the two syndromes. PMID- 8348821 TI - Focal retrograde amnesia in neurological disease: a critical review. AB - The condition of focal retrograde amnesia represents a new and challenging concept to our understanding of human memory disorders. Cases of both permanent and transient focal retrograde amnesia, dating from early clinical descriptions to more recent experimental reports, are critically reviewed. It is concluded that the condition of focal retrograde amnesia does represent a distinct and reliable neurological entity. Four sets of issues are discussed--methodological issues, conceptual issues, anatomical issues and therapeutic issues. Current evidence indicates an important role for temporal lobe structures in mediating focal retrograde amnesia. Both storage and retrieval deficits may contribute to the presence of focal retrograde amnesia, though available evidence points to a greater role for engram destruction/fragmentation rather than disruption of access mechanisms. In general, pharmacological and other therapies have had minimal effects in alleviating focal retrograde amnesia. PMID- 8348822 TI - Spatial memory in amnesia: evidence from Korsakoff patients. AB - Two experiments are reported which investigated a hypothesised disproportionate deficit in amnesic spatial memory. Korsakoff amnesic memory for the locations of objects or words placed on a grid was compared to control memory which had been attenuated by longer delays before testing. The effects of incidental versus intentional encoding of the locations were compared. No significant evidence of a disproportionate spatial memory deficit in Korsakoff amnesia was found, intentional instructions did not improve Korsakoff amnesic spatial memory scores, and there was no significant evidence of a trade-off of item memory and location memory specific to the Korsakoff amnesic group. Rather, intentional instructions significantly reduced item memory in both Korsakoff amnesics and normal controls, while having no effect on spatial memory. When location was scored by lenient criteria, there was no significant difference between groups for this measure, nor for recall and recognition memory for these items. Thus Korsakoff amnesic memory was very similar to that of control memory attenuated by longer delays before testing. The Korsakoff amnesic subjects' memory therefore differed quantitatively rather than qualitatively from that of control subjects' memory. PMID- 8348823 TI - Encoding deficits in untreated Parkinson's disease. AB - Short-term memory deficits are prominent in untreated Parkinson's Disease (PD) and speed of central processing is known to be abnormal. To investigate the relationship between these findings, a modification of the Brown-Peterson paradigm was given to newly diagnosed, untreated patients and healthy control subjects (HCS). The PD patients were impaired under conditions of long stimulus exposure but not when study time was short. Although patients displayed deficits in immediate recall, they were more impaired at longer test delays. They achieved fewer encoding operations per unit time, resulting in a divergence of group performance with increasing duration of stimulus exposure. Performance in the PD group did not associate with motor disability, disease duration or rating of depression. These results are discussed in terms of a unifying reduced central processing deficit that is evident in PD but is independent of physical symptoms. PMID- 8348824 TI - Impaired temporal context memory on anterograde but not retrograde tests in the absence of frontal pathology. AB - This study examined the memory performance of patient RK who developed substantial memory impairments due to a hypothalamic glioma but in the absence of any evidence of frontal disturbance. RK was evaluated on both tests of anterograde and retrograde memory for temporal context. In the first experiment he exhibited marked deficits on a list discrimination task even when recognition performance was well within control range. Experiment 2 confirmed this disproportionate impairment of temporal order memory and showed that RK's list discrimination deficit was as severe as that found in alcoholic Wernicke Korsakoff Syndrome patients. Experiment 3 showed that RK's temporal discrimination deficit was not a general deficit in discrimination because he performed normally on a spatial discrimination test of comparable difficulty to the temporal task. Experiment 4 examined RK's memory for deceased famous people and his ability to indicate the half decade in which they died. RK's performance was indistinguishable from controls whereas WKS patients were extremely impaired. This study adds to the view that frontal damage is not a necessary condition for impairment on anterograde measures of temporal context memory. However, further evidence from this study indicates that temporal judgments about pre-existing memories may depend on intact frontal lobe functioning. PMID- 8348825 TI - Selective impairment of retrieving people's names: a category specific disorder? AB - A patient with an extremely long-standing low grade glioma affecting the left temporal lobe is described. The patient was almost entirely unable to retrieve the names of current personalities, although in other respects identification was unimpaired and nominal functions were only mildly inefficient. In particular geographical features and historical figures were generally appropriately named. The problem was equally severe whether naming was to confrontation, from description or by generation. A similarly severe impairment was also found for the retrieval of new words that had come into the language in the last twenty years (eg. aids). The impairment of retrieving people's names was interpreted in terms of a long-standing inability to form new associations between meaning and phonological word-forms. PMID- 8348826 TI - A role for the hippocampus in card sorting? AB - This study examines the performance of three groups of patients with epilepsy on three measures typically used to assess the integrity of the frontal lobes: the Modified Wisconsin Card Sorting Test (MWCST), verbal fluency and the Stroop test. The groups comprised sixteen patients with clearly defined hippocampal sclerosis, thirteen patients with unilateral temporal lobe seizure onset and eighteen patients with unilateral frontal lobe onset. Results demonstrated that performance on the MWCST was most compromised by hippocampal sclerosis. These patients took longer to complete the task, achieved fewer categories and made more perseverative errors than patients in the other groups. In contrast, verbal fluency and performance on the Stroop test were less affected by the presence of hippocampal sclerosis. These results have both clinical and theoretical significance. It is argued that patients with hippocampal damage perform poorly on the MWCST because of the heavy working memory requirements of the test. Cautious use of this test as a tool to localise seizure origin in patients with complex partial seizures is therefore recommended. The findings are discussed in terms of Gray's (1982) model of the hippocampus as a comparator of actions. PMID- 8348827 TI - Factor analyses of pooled hand questionnaire data are of questionable value. AB - A number of researches have used factor analyses and principal components analyses on handedness questionnaire data in order to learn something about handedness. However, these researchers have analyzed pooled data from righthanders and lefthanders. The practice of pooling groups that are known in advance to be heterogeneous is highly questionable because it is not possible to disentangle the sources of variance that are contributed by within group differences from those that arise from between group differences. The factor structure and item loadings that result from pooled data are misleading and cannot inform meaningfully about the relation of hand preference to handedness. Similar problems can be anticipated in other neuropsychological applications of factor analysis, where data from heterogeneous groups is pooled. PMID- 8348828 TI - Operant conditioning after temporal lobe lesions in man: conditional and simple discrimination learning. AB - Temporal lobe lesions have been found to impair the acquisition of classical conditional discrimination learning in an eyelid conditioning paradigm, with sparing of simple eyelid conditioning. In the present study, subjects with left or right temporal resections were compared with normal controls on two operant conditioning tasks using a conditional and a simple discrimination paradigm analogous to the previously reported classical conditioning tasks. Subjects with right temporal lesions, and to a lesser extent those with left temporal lesions, were impaired relative to frontal lobe and control subjects in the acquisition of a conditional discrimination within an operant conditioning setting. A subsequent experiment showed that both left and right temporal lobe subjects were unimpaired on a simple operant discrimination task. These findings are compatible with theory relating hippocampal function to the learning of if-then rules. PMID- 8348829 TI - Laterality for facial expressions: does the sex of the subject interact with the sex of the stimulus face? AB - Seventy right-handed subjects (35 males and 35 females) were shown lateralized pictures of negative, neutral, and positive facial emotional expressions. For each emotional category, half of the pictures were of a male face showing the emotion, half were of a female face. The pictures were shown in the left visual half-field for half of the trials and in the right half-field for the other half of the trials. The question addressed was whether the sex of the stimulus face interacts with the sex of the subject for hemisphere differences in perception of facial emotions. Response accuracy and reaction time were measured. The pictures were shown from a slide projector with a high-speed shutter mounted to the lens to allow for tachistoscopic presentations. The results showed that the right hemisphere was more accurate and faster than the left in recognizing the stimulus faces, and that positive emotions were overall more easily recognized. The lack of a significant interaction between sex of the stimulus and sex of the subject indicates that these two factors are not interrelated or confounded in laterality research. PMID- 8348830 TI - Reaction time improvements with practice in brain-damaged patients. AB - This study investigated practice effects on reaction time (RT) in patients with unilateral brain damage and age-matched controls. Subjects performed a Sternberg type stimulus recognition task. Both RT and RT variability decreased in all subjects from a short initial session to a second session, 1 to 3 days later. Within the second session, however, RT remained constant in the controls, whereas it was further reduced in the patients. These findings argue against the assumption that brain-damaged patients generally show smaller practice effects on RT than controls, and instead suggest that it may be essential to provide patients with sufficient practice opportunities. To locate the processing stage where practice is effective, analyses were performed also on the intercept and slope parameters of the RT function. It is argued that the differential practice effects were due to the speeding of perceptual and/or response-related stages, rather than gains in memory search speed. PMID- 8348831 TI - Phonemic discrimination in callosal agenesis. AB - Children with callosal agenesis have congenital absence of the corpus callosum. Previous analyses of these subjects have shown that they have significant difficulty on rhyming tasks and tasks of explicit sound organisation. This study investigated whether such difficulties were also manifested on simpler tasks requiring the discrimination and repetition of similar sounding linguistic material. None of the acallosal children tested performed at a normal level across tasks. This suggests a possible impairment in the initial registration or analysis of auditory material and possible bases for this deficit are discussed. In cases of callosal agenesis in which impairments in auditory discrimination are more severe there may be a more profound impact upon language development. PMID- 8348832 TI - Evidence for an independent stimulus-centered spatial reference frame from a case of visual hemineglect. AB - Previous experiments with patients suffering from visual hemineglect have provided evidence relevant to the organization of the human spatial representation system. We examined the hypothesis that one reference frame used to represent the location of objects in the environment is based on the spatial extent of the stimulation that needs to be processed at a specific point in time; in current terminology, a stimulus-centered reference frame. The paradigm used was one of filtering, and variation of the location of the target within a horizontal array of items (stimulus-relative location) was independent of the target location relative to the subject and to stable reference points in the environment. Results showed that stimulus-relative target location provided an independent contribution to the magnitude of the neglect symptoms. This is taken as an indication that a stimulus-centered spatial reference frame contributes to the representation of the location of visual objects in human vision and that this representation may serve to direct visual attention. PMID- 8348833 TI - Interhemispheric integration of number stimuli: comparison of Arabic with Kanji numerals. AB - Thirty normal subjects were requested to add two numbers which were presented tachistoscopically. Two numbers were displayed either to one visual field or simultaneously one to the left and one to the right visual field. Arabic or Kanji numerals were used. Bilateral presentation was superior to unilateral presentation with both kinds of stimuli. In unilateral presentation, Arabic numbers were processed more proficiently in the left visual field and Kanji numbers in the right visual field. PMID- 8348834 TI - Silent myocardial ischemia. AB - The documentation of abnormalities related to myocardial ischemia, whether symptomatic or silent, is of central importance. Whenever this information is available, it should be used in the overall assessment of the patient at risk for adverse outcome. The level of concern for treatment of CAD should be based on the risk implications associated with the ischemia-related abnormalities detected during objective testing rather than on the presence or absence of pain. The exercise stress test is still the single most useful test to begin the evaluation of a patient with an analyzable ST segment. In persons suspected of having CAD, the detection of ischemic-type ST-segment depression, at a low workload (e.g., < 120 beats/min or < 6.5 METS) of > 2 mm magnitude or persisting for more than 6 min implies high risk for adverse outcome. Asymptomatic ischemia during everyday activities, detected by Holter monitoring, in the high-risk patient, most probably adds additional risk beyond the risk of an abnormal stress test alone. Left ventricular imaging by two-dimensional echocardiography, RNA, angiogram, vest, etc, showing an ejection fraction > or = 40%, reversible wall motion abnormalities in multiple regions and redistribution defects or a failure to increase ejection fraction during exercise even if the patient remains asymptomatic, also imply high risk. The presence of any of these abnormal findings, regardless of symptoms, should therefore prompt as high a degree of concern as with ischemia-related signals associated with pain. Thus any therapy chosen should be directed toward elimination of transient ischemia, not just relief of symptoms that may or may not be ischemia related. If this course is chosen, the efficacy of the therapeutic regimen and possible progression of CAD should be assessed with follow-up testing for ischemia. We believe that risk factor modification and aspirin should be considered for most, if not all, patients in whom ischemia, silent or symptomatic, is suspected or detected. If symptoms or ischemia suggesting low risk is present, anti-ischemic medical therapy may be considered, but follow-up is advised. If a high-risk ischemic signal, even without symptoms, is detected, medical therapy should be used to attempt to modify the signal. If the ischemic signal suggesting high risk persists despite medical therapy, revascularization should be considered. Until additional data from large clinical trials are available, this approach appears to have the greatest likelihood of modifying the adverse outcome of CAD. PMID- 8348835 TI - Current usefulness of the signal-averaged electrocardiogram. AB - Signal-averaged electrocardiography is a relatively simple, noninvasive technique by which valuable information can be gained to help in the management of patients with cardiovascular disease. The presence of late potentials on the SAECG is a good marker for the presence of an arrhythmogenic substrate that is believed to be the source of ventricular tachycardia in patients with coronary artery disease. The value of the detection of late potentials has been studied best after myocardial infarction, when the absence of late potentials makes the occurrence of an arrhythmic event very unlikely. The positive predictive value for an arrhythmic event to occur in the presence of late potentials is low, however, comparable to the predictive value of decreased left ventricular function, complex ventricular ectopy, or abnormal autonomic tone. This appears to have its explanation in the complex pathophysiology behind the occurrence of arrhythmic events. Improved accuracy for the SAECG is achieved when the result of the test is interpreted with consideration of the presence or absence of other predictive markers. A thorough understanding of the signal-averaged electrocardiogram makes optimal clinical use of the information gained from this easily acquired test possible. PMID- 8348836 TI - Mitral valve disease. PMID- 8348837 TI - Aortic valve replacement. PMID- 8348838 TI - Lateral inhibition and pattern formation in Dictyostelium. PMID- 8348839 TI - Cell cycle control during mammalian oogenesis. PMID- 8348840 TI - Axis determination in the avian embryo. PMID- 8348841 TI - Gene and enhancer trapping: mutagenic strategies for developmental studies. PMID- 8348842 TI - Genetic and molecular analysis of leaf development. PMID- 8348843 TI - Drosophila cell adhesion molecules. PMID- 8348845 TI - Racial inequality and child neglect: findings in a metropolitan area. AB - Despite contradictory evidence, child neglect is often believed to occur more frequently in the African American than in the Caucasian population. This article reports findings on the racial differences among 182 families referred for neglect in a large metropolitan area. Although almost all of the families were poor, African American families in the neglect sample suffered even more from economic inequality than those in the general population. Implications of the findings for social welfare policy and child welfare practice are discussed. PMID- 8348844 TI - Child welfare services for the catastrophically ill newborn: Part I--A confusion of responsibility. AB - The majority of these difficult bioethical decisions should properly be made by parents with input from physician and health care workers, utilizing the resources and guidance of infant ethics committees within the involved hospitals. The child protective service system should have the final authority, however, to assure that the decisions of the "caregivers" do not constitute abuse or neglect. This will require that the child welfare system sometimes walk the razor's edge between protecting the child's best interests and preserving, facilitating, and empowering families in these difficult circumstances. But this is an ethical dilemma the child welfare system negotiates daily, and is perhaps the reason used to justify assigning the child welfare system this responsibility. It will also require that the child welfare field have a consensus bioethical paradigm for treatment decision-making for children born with catastrophic illness. Consistent treatment decisions in the best interests of our most vulnerable children cannot be assured, or even expected, without such standardized guidelines. PMID- 8348846 TI - Development of an integrated case management program for vulnerable children. AB - Although case management is a recognized technique to organize and coordinate human services, its use with high-risk children is relatively new. This article describes the development of a case management program for children at the Center for the Vulnerable Child at Children's Hospital, Oakland, California, a health care setting that brings together health, social work, and child welfare services. Case management was introduced into multidisciplinary clinical programs for foster children, drug-exposed infants, and adolescent mothers and their infants. Case management activities differed in each of the clinical programs in relation to the unique characteristics of each population and the different obstacles encountered. A time management analysis indicated consequent differences in case management time allocations. The implications of these findings are discussed. PMID- 8348847 TI - Prognostic value of tumor "budding" in patients with colorectal cancer. AB - From 1970 to 1985, 663 patients underwent curative resection of colon and rectal adenocarcinomas. All surgical specimens were examined for tumor "budding," defined as small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion. Patients were divided into two groups according to degree of budding: none or mild (BD-1) and moderate or severe (BD-2). BD-1 occurred in 493 patients (74.4 percent), and BD-2 was found in 170 patients (25.6 percent). More severe budding was associated with worse outcome: 71.1 percent of BD-2 patients had recurrence, compared with 20.0 percent of BD-1 patients (P < 0.005). The five year survival rate was worse in BD-2 than in BD-1 (22.2 percent vs. 70.7 percent; P < 0.001). The 10-year survival rate was also worse in BD-2 than in BD-1 (13.8 percent vs. 50.6 percent; P < 0.001). The incidence of BD-2 rose with the Dukes stage. However, the five-year survival rate of Dukes B patients with BD-2 lesions was worse than that of Dukes C patients with BD-1 cancers (29.1 percent vs. 66.2 percent; P < 0.001). Moreover, there was no difference in five-year survival among BD-1 patients with either Dukes B or C lesions (68.3 percent vs. 66.2 percent). The presence of more severe budding appears to indicate a vigorous biologic activity of colorectal cancer. Thus, meticulous follow-up--and possibly adjuvant chemotherapy--may be beneficial for patients with marked budding, regardless of their Dukes stage. PMID- 8348848 TI - Is follow-up of colorectal cancer patients worthwhile? AB - Between 1978 and 1989, 1,045 of 1,399 patients (580 male and 474 female) underwent curative surgery for colorectal carcinoma. Of these patients, 350 (33 percent) had recurrences, another 16 (1.5 percent) developed a metachronous colorectal cancer, and 23 (2 percent) had cancers of other organs. An isolated locoregional recurrence was found in 75/350 (21 percent). The remaining 275/350 patients (79 percent) showed systemic dissemination of the carcinoma. Reoperations with curative intent were performed on 56/350 patients (16 percent). Only 21 of the 56 resected patients (38 percent), i.e., 21/350 (6 percent), were without recurrence at the end of the follow-up period on December 31, 1990. Despite a curative reoperation, 62 percent of the patients again developed recurrent growths. There is an imbalance between the efforts invested in tumor follow-up and the benefits gained. Further follow-up programs should be investigated in a controlled, prospective fashion. PMID- 8348849 TI - Adenocarcinoma complicating Crohn's disease. AB - We report on 14 cases of intestinal adenocarcinoma complicating Crohn's disease, seven occurring in the small bowel and seven in the large bowel. In both locations, two-thirds of patients were male. The average ages at the time of diagnosis of Crohn's disease and of cancer were similar between the two groups of patients: 28 and 48 years, respectively. The diagnosis of cancer was suspected or obtained preoperatively in only four cases of large bowel cancer; in two patients with large bowel cancer and five with small bowel cancer, the diagnosis was made at laparotomy. In the remaining cases, only careful histologic examination revealed the carcinoma. Six small bowel cancers were located in the ileum, and five colonic cancers were distal to the splenic flexure. Two small bowel and one large bowel cancer were multifocal and had surrounding mucosal dysplasia. All tumors, except one small bowel cancer, underwent resection. Survival correlated with stage of tumor at resection; no patient with regional or distant metastasis survived five years, in comparison with an 83 percent five-year actuarial survival rate of patients with tumor confined to the intestinal wall. Mean survival was six months for patients with small bowel cancer in comparison with 65 months for patients with large bowel cancer, reflecting a tendency toward more advanced lesions in the small bowel cancer group. PMID- 8348851 TI - Cinedefecography and electromyography in the diagnosis of nonrelaxing puborectalis syndrome. AB - A prospective study was undertaken to assess the correlation between electromyography (EMG) and cinedefecography (CD) for the diagnosis of nonrelaxing puborectalis syndrome (NRPR). Clinical criteria for NRPR included straining, incomplete evacuation, tenesmus, and the need for enemas, suppositories, or digitation. EMG criteria included failure to achieve a significant decrease in electrical activity of the puborectalis (PR) during attempted evacuation. CD criteria included either paradoxical contraction or failure of relaxation of the PR along with incomplete evacuation. In addition, other etiologies for incomplete evacuation, such as rectoanal intussusception or nonemptying rectocele, were excluded by proctoscopy and defecography in all cases. One hundred twelve patients with constipation, 81 females and 31 males, with a mean age of 59 (range, 12-83) years were studied by routine office evaluation, CD, and EMG. Forty-two patients (37 percent) had evidence of NRPR on CD (rectal emptying: none, 24; incomplete, 18). Twenty-eight of these patients (67 percent) also had evidence of NRPR on EMG. EMG findings of NRPR were present in 12 of 70 patients (17 percent) with normal rectal emptying. Conversely, 14 of 72 patients (19 percent) with normal PR relaxation on EMG had an NRPR pattern on CD. The sensitivity and specificity for the EMG diagnosis of NRPR were 67 percent and 83 percent, and the positive and negative predictive values were 70 percent and 80 percent, respectively. Conversely, if EMG is considered as the ideal test for the diagnosis of NRPR, CD had a sensitivity of 70 percent, a specificity of 80 percent, and positive and negative predictive values of 66 percent and 82 percent, respectively. In summary, sensitivity, specificity, and predictive values of EMG and CD are suboptimal. Therefore, a combination of these two tests is suggested for the diagnosis of NRPR. PMID- 8348850 TI - Polyamines, diamine oxidase, and ornithine decarboxylase activity in colorectal cancer and in normal surrounding mucosa. AB - We investigated the polyamine levels [putrescine (Put), spermidine (Spd), and spermine (Spm)] and their metabolism by simultaneously considering the ornithine decarboxylase (ODC) and diamine oxidase (DAO) activities in human colorectal cancer and in normal surrounding tissue. Single and total polyamine levels were significantly higher in the neoplastic tissue than in the surrounding mucosa from the same patients. Furthermore, the ODC activity was significantly higher and the DAO activity significantly lower in the neoplastic tissue than in the surrounding mucosa. Polyamine levels and enzymatic activities did not correlate with the clinical and histologic characteristics of patients. In normal tissue samples, no correlation was found between single and total polyamine levels and enzymatic activities (both DAO and ODC). On the contrary, in colorectal neoplastic samples, significant and positive correlations were found between the levels of total polyamines, Spd, and Spm and the ODC activity. In the same specimens, DAO activity was related to Spd levels and the Spd/Spm ratio, but, in those cases, the correlation was negative. Thus, our findings suggest that, during the neoplastic growth of the colorectal mucosa, the balance between polyamine degradation and biosynthesis is disengaged from the control exerted by the two enzymes. PMID- 8348852 TI - Risk of sphincter damage and anal incontinence after anal dilatation for fissure in-ano. An endosonographic study. AB - Follow-up was performed two to six years after anal dilatation for fissure-in-ano in 32 consecutive patients who had not undergone additional anal surgery. All patients were interviewed and asked specifically about impairment of flatus or fecal control and its possible relation to the anal dilatation. Anal dilatation was followed by minor anal incontinence in 12.5 percent of the patients. Anal endosonographic follow-up was accepted by 20 patients, and sphincteric defects were found in 13 (65 percent) of those. Two patients with anal incontinence had internal sphincter defects. Sphincteric defects were also found in 11 of the 18 continent patients who underwent sonography: internal sphincter defects in nine, external sphincter defect in one, and combined defects of both sphincter muscles in one. In conclusion, anal dilatation results in sphincter damage in more than half of patients, but few of them develop anal incontinence. PMID- 8348853 TI - Protective effect of RibCys following high-dose irradiation of the rectosigmoid. AB - Ribose-cysteine (RibCys) is a prodrug of L-cysteine that stimulates glutathione biosynthesis. Increased glutathione levels have been shown to have a protective effect against radiation-induced injury and oxidative stress. Surface oximetry has previously been used successfully to predict anastomotic leakage. PURPOSE: The following study was done to evaluate the protective effect of RibCys and the predictive value of PtO2 determinations in a swine model. METHODS: Domestic swine were divided into three groups: Group A served as a nonradiated control; Group B received 6,000 to 6,500 rad to the rectosigmoid; and Group C received RibCys (1 g/kg) prior to receiving 6,000 to 6,500 rad. Radiated animals and controls underwent rectosigmoid resection after a three-week rest period. Intraoperative anastomotic PtO2 was checked with a modified Clark electrode. Anastomoses were evaluated radiographically at three and seven days; animals were sacrificed, and bursting strength was recorded at 10 days. RESULTS: Mean bursting pressures were 243.8 +/- 59.4, 199.5 +/- 37.8, and 209.5 +/- 54.9 mmHg (NS) for Groups A, B, and C, respectively. Anastomotic PtO2 ranged from 19 to 98 mmHg and could not be correlated with anastomotic leaks or bursting pressure. There were 11/15 radiation-related deaths and leaks (eight deaths and three leaks) in the radiated group and 4/12 radiation-related deaths and leaks (three deaths and one leak) in the group receiving radiation and RibCys (P < 0.04). CONCLUSIONS: 1) RibCys protected animals against radiation-related deaths and anastomotic leaks following high doses of pelvic irradiation; 2) anastomotic PtO2 levels did not correlate with anastomotic healing in this model. PMID- 8348854 TI - Endoluminal ultrasound is preferable to electromyography in mapping anal sphincteric defects. AB - Assessment of complex sphincteric defects in patients with fecal incontinence by digital rectal examination and intraoperative dissection can be difficult in the presence of excessive scarring. Adjunctive investigation such as endoluminal ultrasound (ELUS) and needle electromyography (EMG) may provide objective evidence of the nature and extent of the sphincteric defects. In a series of 11 patients, ELUS of the anal canal with a 10-MHz transducer (focal zone of 1-4 cm) accurately detected defects in the external anal sphincter (EAS) in seven of seven patients, defects in the internal anal sphincter (IAS) in eight of eight patients, and integrity of both sphincters in two patients. These findings were confirmed by needle EMG of the EAS alone in five patients, by operative findings at a perineal sphincteroplasty operation in six patients, and by both in two patients. ELUS was associated with less pain than was needle EMG (pain score 4 vs. 10, 10 being most painful) and provided high-resolution radial images of both the EAS and the IAS. Thus, ELUS seems preferable to EMG in mapping anal sphincteric defects and can be a useful anatomic adjunct to physiologic studies of anorectal function in patients with fecal incontinence. PMID- 8348855 TI - Laparoscopic-assisted full-thickness endoscopic polypectomy. AB - PURPOSE: To describe the procedure for endoscopically removing sessile colonic polyps with laparoscopic assistance. METHODS: Technique description and retrospective review of experience. RESULTS: The technique has been used to successfully remove polypoid colonic lesions in three patients. CONCLUSIONS: Laparoscopic-assisted polypectomy allows complete excision of moderate-sized sessile polyps and may spare selected patients a colonic resection. PMID- 8348856 TI - Prokinetic agents for lower gastrointestinal motility disorders. AB - Prokinetic agents are currently being investigated as potential therapies for motility disorders of the lower gastrointestinal tract. Cholinergic agonists such as bethanechol are known to improve postoperative ileus but are limited because of side effects. Dopamine antagonists such as domperidone appear to have maximal prokinetic effect in the proximal gastrointestinal tract and are effective for such conditions as gastroparesis and gastroesophageal reflux, but they appear to have little physiologic effect in the colon or in colonic motility disorders. Naloxone, an opioid antagonist, appears to hold promise in patients with irritable bowel syndrome, small intestinal pseudo-obstruction, and constipation. Erythromycin exerts its prokinetic effect by acting as a motilin agonist; it has been used in the treatment of diabetic gastroparesis and appears to improve symptoms of colonic pseudo-obstruction and postoperative ileus. Metoclopramide, a combined cholinergic agonist and dopamine antagonist, is currently used exclusively for proximal motility dysfunction. Cisapride appears to hold the most promise for patients with colonic motility disorders. In patients with postoperative ileus, cisapride is associated with an increased return of bowel function compared with placebo. In patients with chronic constipation, cisapride increases stool frequency and decreases laxative abuse in both adults and children. Hopefully, as an understanding of gastrointestinal motility increases, effective prokinetic agents will be developed that will improve symptoms of patients with large bowel motility disorders and may also help to predict those patients who benefit from surgical management for constipation. PMID- 8348857 TI - Combined therapy for cancer of the anal canal: a preliminary report. 1974. PMID- 8348858 TI - The colorectal surgeon's scientific and economic responsibility. PMID- 8348859 TI - Electrogalvanic stimulation for levator syndrome: how effective is it in the long term? AB - Levator syndrome is a symptom complex of severe pain and pressure in the anorectal area. Electrogalvanic stimulation (EGS) has been proposed as a treatment for this condition. Several reports have described EGS as up to 90 percent "effective" in treating levator syndrome, but the length of follow-up was uncertain or short-term in these studies. The purpose of this study was to examine the long-term benefits of EGS in levator syndrome patients treated at one institution. All patients undergoing EGS for levator syndrome between 1985 and 1991 were studied. Initial complaints, physical examination, number of treatments, procedure tolerance, and long-term benefit were determined through personal interviews and chart reviews. There were 52 patients (63 percent females and 37 percent males) with a median age of 54 years (range, 24-84 years). All patients presented with anorectal pain. Tenderness was localized by examination to the left in 43 percent, to the right in 23 percent, and bilateral in 8.6 percent and was not localized in 2.6 percent. Fifty percent received fewer than four one-hour treatments, 33 percent received four to six treatments, and 17 percent received more than six treatments. Seventy-seven percent felt that the treatment was painless. Follow-up results were as follow: number, 52; percent follow-up, 88; mean follow-up, 28 months (range, 0-71 months); symptoms relieved, 19 percent; partial relief, 24 percent; no relief, 57 percent. Of four patients with a wrong diagnosis, three were ultimately diagnosed with recurrent pelvic cancer and one had an anal fissure. At our institution, EGS was a tolerable treatment, but a substantial number of patients received no benefit. An organic etiology of anorectal pain must always be excluded. PMID- 8348860 TI - Do general surgery residency programs adequately train surgeons to perform anorectal surgery? AB - The management of anorectal disease remains a major component in the practice of the general surgeon. To assess the adequacy of general surgery residencies in addressing this educational need, data were obtained from the Residency Review Committee (RRC) for surgery on the anorectal experience of all graduating residents in accredited United States programs for a recent five-year period (1987-1991). The mean number of anorectal procedures in which a resident participated throughout the residency was 30.0. This is then further subdivided by type of procedure. It is concluded that general surgery residency programs tend to provide an inadequate training experience in anorectal surgery. PMID- 8348861 TI - Incidence of surgical resection for Crohn's disease. AB - One hundred fifty-two of 399 Crohn's patients (38 percent) diagnosed over 20 years, who lived within a geographically defined area at the time of diagnosis, underwent at least one operation. One hundred seventy-one resections were performed in 160 operations during a mean follow-up of 60 months. Forty-eight percent of patients had undergone their first resection within 10 years of diagnosis, and 39 percent of these had undergone a second resection within 10 years of the first. There was no difference between smokers and nonsmokers in the timing of their surgery. PMID- 8348862 TI - Clinical assessment of the anal continence plug. AB - Recently, promising results with different modifications of an anal continence plug were reported in a pilot study. We have performed a clinical assessment of the plug preferred by the majority of patients in this study in an ambulatory group of patients incontinent to liquid and solid stool. Nine of 14 patients (64 percent; 95 percent confidence interval: 35-87 percent) were continent when they used the plug. In 43 percent (18-71 percent), the plug occasionally slipped out, and 71 percent (42-92 percent) experienced discomfort to a varying degree, which caused 11 patients to withdraw from the study before the end of the planned study period. No correlation was found between the results of anorectal physiology studies and the benefit or inconvenience of using the plug. The overall conclusion is that the majority of patients would use the plug under special circumstances because it eliminates the fear of fecal leakage but that local discomfort, possibly due to the material, would prevent its daily use. PMID- 8348863 TI - Outcome of delayed hemorrhage following surgical hemorrhoidectomy. AB - Delayed hemorrhage following surgical hemorrhoidectomy is a well-recognized complication. Emergency treatment may include suture ligation, anal packing, or other means of tamponade. At the Lehigh Valley Hospital, 27 patients were seen with the complication of delayed hemorrhage over an eight-year period from 1983 to 1990, for an incidence of 0.8 percent. Twenty-five patients (93 percent) underwent surgery primarily for hemorrhoidal disease; one patient had hemorrhoids removed in addition to a sphincterotomy for anal tissue, and the remaining patient had hemorrhoidectomy with fistulotomy. The mean interval from the operation to hemorrhage was six days. Treatment modalities included bedside anal packing in 20 patients (74 percent), observation alone in five patients (18 percent), and suture ligation in the operating room in two patients. Anal packing was successful in controlling postoperative hemorrhage in 20/20 patients, but late complications requiring reoperation developed in 15 percent. PMID- 8348864 TI - Laparoscopic-assisted bowel surgery. AB - The use of laparoscopic surgical techniques is now being applied to a variety of operations traditionally performed in an open fashion. Twenty patients underwent laparoscopic-guided large and small bowel surgery at our institution from March 1991 to April 1992. The indications for surgery included polyps, obstruction, bleeding, and perforation, and pathologic diagnoses included benign polyps, lipomas, inflammatory bowel disease, perforation of a jejunal diverticulum, colonic arteriovenous malformations, and adenocarcinoma. Mobilization of the colon, ligation of the mesentery, and closure of the mesenteric defect were performed using the laparoscopic equipment. One trocar site was enlarged to 3 cm to deliver the bowel through the abdominal wall. All anastomoses were hand-sewn. Postoperative hospitalization ranged from 2 to 31 days (median, five days). No mortality was noted, and morbidity was 20 percent. We conclude that laparoscopic guided bowel surgery is technically feasible and should translate into shorter hospitalization and less patient discomfort. PMID- 8348865 TI - Minimally invasive colectomy: are the potential benefits realized? AB - Laparoscopic surgical techniques have recently been applied to various types of colon resection. Early reports have focused on the technical feasibility of these procedures, and it has not yet been clearly shown that such procedures benefit the patient. We reviewed our experience with 28 attempted minimally invasive colectomies (MICs) performed over a nine-month period. Laparoscopic or laparoscopic-assisted resections were successfully completed in 24 of these patients. We compared the results of surgery in these 24 patients with a group of 33 patients undergoing similar procedures at the same institution by the same surgeon in the nine months preceding the laparoscopic experience. The two groups of patients were similar with respect to age, weight, and the types of procedures performed. However, the postoperative length of stay for patients undergoing MIC (4.8 days) was significantly shorter than for those undergoing open colectomies (8.2 days). Patients undergoing MIC also regained bowel function significantly earlier than those undergoing open colectomy. The operative times for the minimally invasive procedures were significantly longer than for those undergoing open colectomy. No surgically related deaths were encountered, and morbidity was 13 percent. None of the four patients converted from laparoscopic to open colectomy suffered complications as a result of the attempted laparoscopic procedure. We conclude that MIC can be safely performed and does appear to reduce the duration of postoperative ileus and decrease the length of postoperative hospitalization. PMID- 8348866 TI - Fecal diversion in the management of Crohn's disease of the colon. AB - The clinical course of 44 patients undergoing elective proximal fecal diversion for Crohn's disease of the colon is reported. Sustained disease remission was obtained in 31 patients (70 percent). Diversion was associated with a significant reduction in steroid requirements (P < 0.01) and a significant improvement in hemoglobin (P < 0.001), erythrocyte sedimentation rate (P < 0.001), and albumin (P < 0.05). Sixteen patients (36.4 percent) have required a proctocolectomy, 19 patients (43.2 percent) remain defunctioned, and four patients (9 percent) have died. Five patients have had intestinal continuity restored, which has remained intact in four patients for a mean follow-up of 99 (range 21-153) months. Fecal diversion for Crohn's disease of the colon produces a high incidence of sustained disease remission, but for the majority of patients the prospect of future restoration of intestinal continuity is limited. PMID- 8348867 TI - Diagnostic laparoscopy: reducing the number of normal appendectomies. AB - A prospective, controlled study was conducted to determine whether a selective policy of diagnostic laparoscopy could reduce the number of unnecessary normal appendectomies in patients with acute right iliac fossa pain. The cohort consisted of patients admitted with acute right iliac fossa pain by the emergency department. Of 102 patients in the study group, 28 subsequently required a diagnostic laparoscopy when a definite diagnosis could not be reached after 8 to 12 hours of observation. Of these, only 18 had inflamed appendices, which were removed. In the rest of the patients (10), the appendices were normal and unnecessary laparotomies were avoided. In the control group, wherein equivocal cases were laparotomized after a similar period of observation, there was a normal appendectomy rate of 15.7 percent (P < 0.05). There was no significant difference in the incidence of perforation between the control and study groups. Diagnostic laparoscopy in equivocal cases could thus significantly reduce the number of unnecessary appendectomies without compromising on the rate of perforation. PMID- 8348868 TI - Perineal rectosigmoidectomy in the elderly. AB - Between April 1989 and October 1991, 20 consecutive patients underwent perineal rectosigmoidectomy and coloanal anastomosis for full-thickness rectal prolapse. These 16 females and 4 males, with a mean age of 82 (range, 68-101) years, were evaluated by detailed functional assessment and physiologic testing. A grading scale from 0 to 24 was based upon the frequency and type of incontinence, 0 representing full continence. The mean preoperative continence score was 14.5, while the mean postoperative continence score was 8.4. The mean length of resected rectosigmoid was 23 cm. There was one postoperative death and one significant complication, a postoperative pelvic hematoma that required reoperation. There were no full-thickness recurrences at a mean follow-up of 26 months. Six of the 10 patients who underwent preoperative pudendal nerve terminal motor latency (PNTML) testing had evidence of severe neuropathy (latencies greater than 2.5 milliseconds). Prolonged PNTML, however, was not shown to be an accurate predictor of postoperative incontinence because four of the six patients with neuropathy regained excellent to good control. In conclusion, perineal rectosigmoidectomy is a safe operation for the treatment of full-thickness rectal prolapse in the elderly patient. Improved postoperative continence was noted in 90 percent of patients, with improvement seen even in those patients with severe pudendal neuropathy. PMID- 8348869 TI - Toxic epidermal necrolysis--an unusual cause of colonic perforation. Report of a case. AB - Toxic epidermal necrolysis (TEN) is a rare and severe reaction to certain drugs that results in full-thickness epidermal necrosis of the skin. Other mucosal surfaces such as the oropharynx, esophagus, conjunctiva, and genitalia may also be affected. Specific involvement of the colon is distinctly unusual. A case of TEN that resulted in complete small bowel necrosis and colonic perforation is reported. Early and aggressive surgical resection dealt successfully with this complication and, along with supportive care, allowed resolution of the systemic condition to occur. Five additional cases of colonic necrosis complicating TEN are reviewed. PMID- 8348870 TI - Simple technique for anvil insertion in stapled circular colorectal anastomoses. AB - The benefits of circular stapling devices are obvious. The introduction of staplers with detachable anvils has simplified the stapling procedure even more than the original instruments. A simple technique for placing the anvil and pursestring are described. PMID- 8348871 TI - Pharmacologic treatment of colonic pseudo-obstruction. PMID- 8348872 TI - Relationship between parity and anal manometry. PMID- 8348873 TI - Limits of habituation and extinction: implications for relapse prevention programs in addictions. AB - Problems in the application of exposure techniques to the management of long term dishabituation in addicts are discussed in the light of human and animal evidence. Extinction and habituation of responses to drug cues or drug aftereffects are unstable and strongly dependent on context, thus limiting the effectiveness of cue exposure treatments in the prevention of relapse. Several strategies are suggested to improve the stability of extinction and habituation in order to enduringly prevent relapse in addictions. (i) Warning patients about the episodic resurgence of unexpected urges or cravings precipitated by conditioned contexts and exposing them to such contexts. (ii) To obtain a maximum protection against relapse, extinction should 'recreate' all the original learning contexts (i.e. all possible drug cues). (iii) The behavioral chains involved in self administering drugs ought to be incorporated into cue exposure treatments (without permitting consummatory responses) in order to decrease their signal value as cues for drugs. PMID- 8348874 TI - Triazolam and ethanol effects on human matching-to-sample performance vary as a function of pattern size and discriminability. AB - The effects of placebo, triazolam (2.0, 4.0 and 8.0 micrograms/kg) and ethanol (0.25, 0.5, 1.0 g/kg) on perceptual-motor performance were examined using a visual pattern matching-to-sample procedure in which pattern size and comparison stimulus discriminability were systematically varied. Baseline response rates and accuracy increased as the discriminability of the comparison stimuli increased. At the highest dose, both drugs decreased response accuracy. This disruption of accuracy was attenuated by increasing the discriminability of non-matching stimuli. Triazolam produced dose-related decreases in response rate while ethanol produced only slight decreases at the highest baseline rates of responding. Thus, triazolam produced response rate slowing at relatively lower doses than ethanol. PMID- 8348875 TI - Caffeine self-administration and withdrawal: incidence, individual differences and interrelationships. AB - In four prior studies, caffeine (100 mg) self-administration was assessed by greater self-administration of caffeinated coffee than decaffeinated coffee and caffeine withdrawal was assessed by placebo substitution using six double-blind tests in each subject. This paper collates data across these studies to examine the incidence and predictors of the occurrence of caffeine self-administration and withdrawal. Caffeine self-administration occurred in 31% of subjects when a consistency criterion was used (n = 41) and 27% when a statistical criterion was used. Caffeine withdrawal occurred in 35% and 49% of subjects with each criteria (n = 37). Subjects who had withdrawal headaches and drowsiness were 2.3-2.6 times more likely to self-administer the caffeinated coffee. Several variables (e.g., average caffeine intake) did not predict caffeine self-administration or withdrawal. PMID- 8348877 TI - The dual use of opioids and temazepam by drug injectors in Glasgow (Scotland). AB - In recent years much attention has been drawn to the use of buprenorphine (Temgesic) by heroin injectors in Glasgow and elsewhere. Glasgow has also witnessed a parallel increase in use of the benzodiazapine temazepam, often used as a 'cocktail' with buprenorphine. This paper presents new evidence that, although buprenorphine use among Glasgow drug injectors may now be declining, the use of temazepam-opioid cocktails has continued. PMID- 8348876 TI - Tolerance to self-administration of cocaine in rats: time course and dose response determination using a multi-dose method. AB - To assess tolerance to cocaine in a self-administration paradigm, rats were trained to self-administer cocaine (0.25 mg/injection) on a fixed-ratio 2 (FR2) schedule of reinforcement. The development of tolerance was studied during chronic administration of cocaine (20 mg/kg per 8 h for 10 days), given either contingently (self-administered by the rats) or non-contingently (infused by the experimenter). Both contingent and non-contingent administration of cocaine produced comparable tolerance, as indicated by a faster rate of cocaine self administration (the average inter-reinforcer time, ISRT, decreased significantly). Tolerance developed by day 2 of the chronic regimen and reached a floor value (60% of baseline) from day 4 through day 10. Termination of chronic cocaine then resulted in recovery from tolerance, with ISRTs returning to baseline within 6 days of termination. A second set of experiments determined whether tolerance could be studied using a multi-dose method to obtain dose response data in a single session. A system of multiple pumps allowed testing of three doses of cocaine during a single experimental session. Cocaine dose response curves obtained from the multi-dose method: (i) did not differ from that obtained from a single-dose method; (ii) were reproducible; and (iii) were shifted to the right by Schering 23390. Rats were then subjected to a 7-day chronic regimen of infused cocaine (20 mg/kg per 8 h) or infused saline. At the end of this chronic cocaine period, they were tested with the multi-dose method. Chronic cocaine, as compared to chronic saline, shifted the cocaine dose-response curve to the right, indicating that the multi-dose method can be successfully applied to demonstrate tolerance to the effects of cocaine in a self administration paradigm. PMID- 8348878 TI - Street sale of heroin--a profitable way of making a living? AB - The aim of the study was to give an outline of the financial environment of heroin-sale at street level in Norway and the possibilities of making retail sale of heroin a living. Data were gathered through police records and interviews with informants at street level. Retail sale price has been nominally stable at 300 Nkr (28 pounds, i.e., 1 pound = 11 Nkr) per end-user dose since 1978. This price is coupled to the price of one standard service by street prostitutes. Both the end-users and retailers formally make their living from social welfare payments. The retailer purchases from a wholesaler batches of up to 10 g of heroin at a cost of 50,000 Nkr (4800 pounds). At monthly intervals of delivery this yields 120,000 Nkr (11,500 pounds) as net tax-free income per year, on top of the social welfare payments, even when the retailer and his accomplice consumes a third of the purchased quantity. Crime of gain on the part of the retailer is negligible, due to increased risk of also disclosing his drug trafficking. PMID- 8348879 TI - Helicobacter pylori infection--when and how to treat. PMID- 8348880 TI - Femidom--a condom for women. PMID- 8348881 TI - Slow-acting antirheumatic drugs. PMID- 8348882 TI - Gonadotropin releasing hormone analogues for endometriosis. PMID- 8348883 TI - Nebulisers in childhood asthma. PMID- 8348884 TI - Aldesleukin for metastatic renal cell carcinoma? PMID- 8348885 TI - Meters for measuring blood glucose at home. PMID- 8348886 TI - Clinical applications of endoscopic ultrasonography in gastroenterology--state of the art 1993. Results of a consensus conference, Orlando, Florida, 19 January 1993. PMID- 8348888 TI - Ergonomics in gastrointestinal endoscopy: what do we need for the future? PMID- 8348887 TI - Endoscopic therapy is wonderful (probably); success brings new challenges. PMID- 8348889 TI - Dieulafoy's lesion of the duodenum; successful endoscopic therapy. PMID- 8348890 TI - Sclerotherapy of duodenal varices using a fibrin tissue sealant. PMID- 8348891 TI - Hydrocele following laparoscopic cholecystectomy. PMID- 8348892 TI - Videolaparoscopic treatment of Meckel's diverticulum. PMID- 8348893 TI - Simple release of an impacted Dormia basket during endoscopic bile duct stone extraction. PMID- 8348894 TI - Removal of a press-through package in the thoracic esophagus using two flexible endoscopes. PMID- 8348895 TI - Management of endoscopic impaction during routine ERCP using "the gastric grip". PMID- 8348896 TI - Isolated gastric tuberculosis: a case report. PMID- 8348897 TI - Colonic tuberculosis. An unusual endoscopic diagnosis. PMID- 8348898 TI - Endoscopic diagnosis and removal of Ascaris lumbricoides from the stomach. PMID- 8348899 TI - Developing a model of quality of life in epilepsy: the contribution of neuropsychology. AB - Three specific issues must be considered in the development of a quality-of-life in epilepsy model and psychometric instrument. These issues are: (a) whether to adopt a narrow versus broad model of quality of life, (b) whether to rely on patient self-reports of quality of life or reports garnered from proxies, and (c) whether to develop a generic versus disease-specific measure of quality of life. In reviewing these issues the contributions of the health services research field, research pertaining to the psychological and social effects of epilepsy, and especially neuropsychology, are pertinent. PMID- 8348900 TI - A procedure for developing a quality-of-life measure for epilepsy surgery patients. AB - In 1990, the NIH Consensus Conference Panel on epilepsy surgery called for the development and use of reliable and valid health-related quality-of-life (HRQOL) measures in epilepsy surgery studies. A HRQOL measure for epilepsy surgery patients has been developed and evaluated. The procedure, which could also be used to develop HRQOL measures for other neurological diseases, entails the following steps: (a) specify desired characteristics of the measure; (b) identify relevant HRQOL areas by reviewing the literature; (c) assemble generic core items and disease-specific supplementary items; (d) pilot test and revise the measure; (e) administer revised measure items to a large sample of epilepsy surgery patients; (f) perform item analysis to evaluate hypothesized item placement within scales; and (g) assess the reliability and validity of the scales. The product of this process, the Epilepsy Surgery Inventory (ESI)-55, is a self report measure of 11 dimensions of HRQOL. It is brief, comprehensive, and reliable; preliminary evidence supports its validity. PMID- 8348901 TI - A new quality-of-life inventory for epilepsy patients: interim results. AB - The process for developing and evaluating a comprehensive, self-report measure of quality of life in epilepsy (QOLIE) is described, and interim results for 64 patients are reported. A test battery of 98 quality-of-life items was constructed with use of the RAND 36-Item Health Survey as a generic core and adding other quality-of-life items, the latter derived from a literature review and expert opinion on areas of importance to people with mild to moderate epilepsy. Seventeen scales tapping unique quality-of-life dimensions were identified from this QOLIE test battery. The battery was administered to 64 adults with mild to moderate epilepsy and their proxies (relative or close friend) on two separate visits 2-3 weeks apart. Patients also completed a neuropsychological test battery on the first visit. Interim analysis of these data demonstrated that 16 of 17 scales on the QOLIE test battery are sufficiently reliable for group comparison: Cronbach's alpha for the 16 scales ranged from 0.73 to 0.88; test-retest reliability ranged from 0.56 to 0.88. Preliminary evaluation of validity confirmed hypothesized correlations between selected QOLIE scales and Profile of Mood State scales. Correlations between patient and proxy scores ranged from 0.29 to 0.69 (all statistically significant at p < 0.005). A more detailed, final analysis of data for over 300 patients currently enrolled in the study will be published later. PMID- 8348902 TI - Research use of the new quality-of-life in epilepsy inventory. AB - Epilepsy is a heterogeneous disease with variable onset and prognosis. In general, patients with epilepsy have neuropsychological impairments. Their educational and occupational achievements may be lower than might be expected for their level of cognition. Some epilepsy patients suffer emotional distress, interictal behavioral disorders, and extreme social isolation. It is obvious that epilepsy and its sequelae impact on the patient's quality of life. What is not clear is the degree to which different factors contribute and the causes for extreme variance across patients. For example, the patients' perceptions of their disease affects quality of life more than actual seizure severity, but the mechanisms underlying this effect are not known. Quality-of-life research in epilepsy is in its infancy. In the future, such research will play an important role in assessing patient suffering, demonstrating the efficacy of treatments and interventions, and influencing medical economic decisions. PMID- 8348903 TI - Clinical uses of the quality-of-life in epilepsy inventory. AB - The quality-of-life in epilepsy (QOLIE) inventory was designed to assess adult epilepsy patients. Responses to a draft 99-question inventory administered to patients with low to moderate seizure frequency will be used to generate two or three separate instruments. The largest and most comprehensive of these will serve as a research tool for investigators and may be helpful in designing studies that compare the effects of approved or investigational antiepileptic drugs. This instrument may also be useful in documenting patient outcomes following expensive diagnostic studies, such as video-electroencephalogram monitoring, or other therapeutic interventions, such as epilepsy surgery. An intermediate-sized instrument may serve as a clinical tool for neurologists and epileptologists. A brief instrument may serve as a quick clinical survey for primary care physicians, neurologists, and specialists in epileptology. The abbreviated clinical inventories are intended to provide rapid assessment of quality-of-life issues in the office setting. Such assessments can help physicians and patients identify previously unrecognized problems and may lead to changes in care. PMID- 8348904 TI - Quality of life in epilepsy: the clinician's view. AB - Quality of life in patients with epilepsy may be impaired by seizures, side effects of medication, and psychosocial problems. Doctors tend to focus their attention on managing the seizures and the side effects, but may not be meeting all of the patient's needs because of differences between their perception of these concerns and the patient's. Further, psychosocial problems often are addressed only superficially or not at all during office visits. The challenge is to integrate quality-of-life issues into clinical practice and to better assess the patient's perception of the disorder, the seizures, and the medications, as they impact on cognitive function, emotional well-being, and social and economic functioning. PMID- 8348905 TI - A clinimetric approach to assessing quality of life in epilepsy. AB - Clinimetrics is a concept involving the use of rating scales for clinical phenomena ranging from physical examinations to functional performance. Clinimetric or rating scales can be used for defining patient status and changes that occur during long-term observation. The scores derived from such scales can be used as guidelines for intervention, treatment, or prediction of outcome. In epilepsy, clinimetric scales have been developed for assessing seizure frequency, seizure severity, adverse effects related to antiepileptic drugs (AEDs), and quality of life after surgery for epilepsy. The VA Epilepsy Cooperative Study seizure rating scale combines frequency and severity in a weighted scoring system for simple and complex partial and generalized tonic-clonic seizures, summing all items in a total seizure score. Similarly, the rating scales for systemic toxicity and neurotoxicity use scores weighted for severity for assessing specific adverse effects typically related to AEDs. A composite score, obtained by adding the scores for seizures, systemic toxicity, and neurotoxicity, represents the overall status of the patient at a given time. The Chalfont Seizure Severity Scale also applies scores relative to the impact of a given item on the patient, without factoring in seizure frequency. The Liverpool Seizure Severity Scale is a patient questionnaire covering perceived seizure severity and the impact of ictal and postictal events. The UCLA Epilepsy Surgery Inventory (ESI-55) assesses quality of life for patients who have undergone surgery for epilepsy using generic health status instruments with additional epilepsy specific items.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348906 TI - PACS and digital imaging--new directions. PMID- 8348907 TI - Image segmentation: methods and applications in diagnostic radiology and nuclear medicine. AB - We review and discuss different classes of image segmentation methods. The usefulness of these methods is illustrated by a number of clinical cases. Segmentation is the process of assigning labels to pixels in 2D images or voxels in 3D images. Typically the effect is that the image is split up into segments, also called regions or areas. In medical imaging it is essential for quantification of outlined structures and for 3D visualization of relevant image data. Based on the level of implemented model knowledge we have classified these methods into (1) manual delineation, (2) low-level segmentation, and (3) model based segmentation. Pure manual delineation of structures in a series of images is time-consuming and user-dependent and should therefore be restricted to quick experiments. Low-level segmentation analyzes the image locally at each pixel in the image and is practically limited to high-contrast images. Model-based segmentation uses knowledge of object structure such as global shape or semantic context. It typically requires an initialization, for example in the form of a rough approximation of the contour to be found. In practice it turns out that the use of high-level knowledge, e.g. anatomical knowledge, in the segmentation algorithm is quite complicated. Generally, the number of clinical applications decreases with the level and extent of prior knowledge needed by the segmentation algorithm. Most problems of segmentation inaccuracies can be overcome by human interaction. Promising segmentation methods for complex images are therefore user guided and thus semi-automatic. They require manual intervention and guidance and consist of fast and accurate refinement techniques to assist the human operator. PMID- 8348908 TI - Data fusion in medical imaging: merging multimodal and multipatient images, identification of structures and 3D display aspects. AB - Data fusion in medical imaging can be seen into two ways (i) multisensors fusion of anatomical and functional information and (ii) interpatient data fusion by means of warping models. These two aspects set the methodological framework necessary to perform anatomical modelling especially when concerning the modelling of brain structures. The major relevance of the work presented here concerns the interpretation of multimodal 3D neuro-anatomical data bases. Three types of data fusion problems are considered in this paper. The first one concerns the problem of data combination which includes multimodal registration (multisensor fusion applied to CT, MRI, DSA, PET, SPECT, or MEG). In particular, the problem of warping patient data to an anatomical atlas is reviewed and a solution is proposed. The second problem of data fusion addressed in this paper is the identification of anatomical structures by means of image analysis methods. Two techniques have been developed. The first one deals with the analysis of image geometrical features to end up with the determination of a fuzzy mask to label the structure of interest. The second technique consists of labelling major cerebral structures by means of statistical image features associated with relaxation techniques. Finally, the paper presents a review of up to date 3D display techniques with a special emphasis on volume rendering and 3D display of combined data. PMID- 8348909 TI - European standardization efforts: an important framework for medical imaging. AB - For several years now, users have been waiting for standards allowing medical images to be exchanged, managed, stored and manipulated. Standards are prerequisites for the development of PACS and IMACS systems. It is because of the lack of standards that PACS have not yet widely been implemented. The ACR-NEMA committee (American College of Radiology--National Electronical Manufactures Association) are developing an image communication standard: DICOM 3.0. This should allow interconnection of different imaging modalities and other PACS nodes. Part of the DICOM 3.0 work will be demonstrated at RSNA 93 with involvement of Europe. In the European Standardization Committee (CEN), the technical committee responsible for the standardization activities in Medical Informatics (CEN TC 251), has agreed upon the directions and the scopes to be followed in this field. They are described in the directory of the European standardization requirements for health care informatics and programme for the development of standard adopted on 28 February 1991 by CEN TC 251. Top-down objectives describe the common framework and items like terminology, security, while the more bottom-up oriented items describe fields like medical imaging and multi-media. Since CEN TC 251 started working, an important coordination took place between Europe and the US and Japan, resulting in a common future approach. CEN TC 251 is setting the scene for a more technologically independent standard on a mid term basis. This standard will first have to be proto-typed before it can be published, because it must be possible to implement the standard, too much complexity will not be accepted by the industry. The European imaging standardization work based on the ISO/IPI standard, will be briefly explained; as well as the general framework model and object oriented model; the interworking aspects, and the relation to ISO standards. One should realize be realised that a standard is needed, which is not too ambitious. Because DICOM 3.0 will be ready soon, Europe has decided to support these activities and will concentrate on the next step to be taken. PMID- 8348910 TI - Digital fluoroscopic radiology: evaluation of the clinical impact. AB - The use of digital image intensifier radiography (DIIR) for examinations in projection radiography is becoming more common. Fluoroscopic controlled contrast studies (barium- or iodine-based), particularly of the gastrointestinal tract, can be performed quickly and easily with a considerable decrease in radiation exposure. A wide dynamic range permits a constant high image quality with fewer incorrect exposures. The limited spatial resolution of large image intensifier input screens is the major drawback of DIIR. Digital image acquisition enables post-processing, digital storage and transfer of images, thus allowing an integration into PACS-systems. Imaging capabilities and clinical applications are described here. PMID- 8348912 TI - A personal-computer semiautomated report-coding system for diagnostic mammography. AB - A computerized report-coding system for diagnostic mammography using a personal computer was developed. Four years' experience with the radiologist-oriented system is presented. The data input time for report generation is in most cases less than 30 seconds by radiologists familiar with keyboard entry. Suspicious and malignant findings are dictated in the conventional way. About 80% of the mammographic examinations at the university Breast Imaging Center were suitable for standardized reporting. Radiologist-generated reports using a personal computer might be an alternative to transcriptionist-oriented systems. PMID- 8348911 TI - HIPIN--a generic HIS/RIS-PACS interface based on clinical radiodiagnostic procedures. AB - Within the EurIPACS HIPIN topic a generic HIS/RIS-PACS interface will be designed, implemented and evaluated. It is generally agreed that integration with the HIS/RIS is essential for the acceptance of PACS in a clinical environment. An interface between HIS/RIS and PACS allows more efficient usage of both systems, better integration of data, better consistency checking on shared data and better security and error handling. Also the PACS performance is improved by using HIS/RIS information to steer the image migration within the PACS. In this paper the functional specifications of the interface are described. These specifications are based on descriptions of clinical radiodiagnostic procedures. The generic interface consists of a common part, and of site specific adapters. The common part is identical for all incarnations and performs message scheduling, processing and logging. The adapters are specific for each communication standard, e.g. ACR-NEMA or HL7, and for each hospital. The interface will be implemented at the radiology department of the Philipps University Hospital in Marburg (Germany) and at the orthopaedic and neuroradiology departments of the hospital of the Free University in Brussels (Belgium). PMID- 8348913 TI - Digital image communication. AB - Networks for digital image communication are an essential prerequisite for picture archiving and communication systems (PACS). The scenario of a 'filmless' radiology is based on the assumption that complete sets of medical images can be transferred throughout the hospital without a noticeable delay even though digital images represent data volumes of a thousand-fold greater size than, for example, office documents. This paper deals with an in-depth analysis of the anticipated image communication requirements in a future PACS environment. It gives a survey of technologies for data communication with emphasis on the basic concepts of established local area networks (LAN) and their limiting factors with respect to the specific PACS demands. Likewise, a description of a network particularly developed to satisfy the users-to-be of PACS systems is included. Furthermore, this paper treats the connection of image data with patients' data, i.e. the interlinking of PACS and RIS/HIS structures. Another topic of interest is the extension of the PACS structure beyond the limits of the individual hospital (extramural PACS operation). Moreover, current standardization attempts are discussed here. PMID- 8348914 TI - Expert systems as a support for radiological diagnosis. AB - Given the fact that despite high expectations, expert systems have still an almost negligible impact on the practice of medicine, the present trends and methods for medical expert systems are discussed. An analysis of the diagnostic process in radiology leads to a discussion about possible computer support and on the conditions of use and acceptance of such systems. PMID- 8348915 TI - Magnetic resonance imaging of the central nervous system in Behcet's disease. AB - Magnetic resonance imaging (MRI) was performed in 25 patients with Behcet's disease, of whom 15 had clinical involvement of the central nervous system (CNS). Brain MRI was abnormal in 11/15 with and in 1/10 without CNS involvement. The most common sites of MR lesions were the cerebral white matter and brainstem. Lesions were also seen in the basal ganglia, cerebellum, optic nerves and spinal cord. The cerebral white matter lesions were always asymptomatic and usually small, whereas the brainstem lesions were often symptomatic and sometimes extensive. Follow-up MRI in 2 patients presenting with brainstem syndromes and treated with immunosuppression showed resolution of a large lesion in 1 patient in whom there was clinical remission, and the development of marked brainstem atrophy in the other who became severely disabled. The pattern of MRI abnormalities may assist the diagnosis and suggests a role for MRI in monitoring the effect of treatment in patients with neurological Behcet's disease. PMID- 8348916 TI - Transient global amnesia: neuropsychological findings after single and multiple attacks. AB - We examined by neuropsychological tests 41 patients who had presented attacks of transient global amnesia (TGA; 31 had single and 10 multiple episodes), comparing them with 41 matched normal controls. Patients with single attacks showed only two impaired memory tasks with respect to controls (immediate and long-term verbal memory), while patients with multiple attacks showed more impaired tasks in memory and visuoperceptual ability. These data confirm that TGA is a benign syndrome, but could leave a few subclinical memory deficits probably exacerbated by repeated attacks. PMID- 8348917 TI - Impact of prematurity and intrauterine growth retardation on neonatal hemorrhagic and ischemic brain damage. AB - Low birth weight and intrauterine growth retardation are well-recognized risk factors for increased mortality, morbidity and poor neurologic outcome. Risk assessment is different considering true preterm (appropriate-for-gestational age, AGA) or growth-retarded (small-for-gestational-age, SGA) infants. Therefore, we carried out a study on the incidence of hemorrhagic (peri-intraventricular hemorrhage, PIVH) and ischemic (periventricular leukomalacia) brain lesions in two groups of AGA and SGA very-low-birth-weight (VLBW) infants. In the study period (1987-1990), 111 VLBW babies (< 1,500 g body weight) were serially studied at days 1, 3 and 7 and weekly until discharge by cerebral ultrasonography (ATL, MK 4, 7.5 MHz). 57 were VLBW-AGA babies (mean gestational age 28 weeks, mean body weight 1,106 g). 54 were VLBW-SGA babies (mean gestational age 31 weeks, mean body weight 990 g). PIVH was graded according to the system of Papile et al. Periventricular leukomalacia was defined as an echodensity (> 3 mm) adjacent to the lateral border of the ventricular body. We noted a higher incidence of PIVH in the AGA group (36.8%) than in SGA babies (18.5%; p < 0.01, Fisher test). The AGA subgroup < 1,000 g body weight had 72.2% PIVH compared to AGA babies > 1,000 g (20.5%; p < 0.01). The same relationship was observed in SGA babies (34.8% in < 1,000 g and 6.4% in > 1,000 g babies). Ischemic brain lesions (periventricular leukomalacia) were equally distributed between AGA and SGA babies (10.5 vs. 3.7%, p > 0.5) independently of body weight category.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8348918 TI - Radiologic correlates of reaction time measurements in olivopontocerebellar atrophy. AB - We measured simple visual and auditory reaction time (RT) and movement time (MT) in 32 patients with olivopontocerebellar atrophy (OPCA) in comparison to 32 control subjects. In addition, we followed 2 approaches to radiologic assessment by computed tomographic scans: subjective (by inspection of films) and objective (by measurement of 4 radiologic ratios at the level of the posterior fossa and 1 ratio at the supratentorial level). All OPCA patients had various degrees of cerebellar atrophy and lengthened RT and MT in comparison to their controls. There were no significant differences in RT and MT performances in patients with mild-moderate versus those with severe cerebellar atrophy as assessed by inspection of their films. OPCA patients with severe versus mild-moderate atrophy evaluated by 3 measures, i.e., brainstem, brachium pontis and fourth ventricle ratios, presented few significantly lengthened RT and MT performances. In contrast, patients with severe atrophy revealed by the midbrain ratio had significantly lengthened RT and MT performances compared to those with mild moderate atrophy assessed by this ratio on 7 of 8 measures; the 8th measure showed a borderline significant difference. This could be explained by the fact that atrophy at the midbrain level is the only one which involves dopaminergic, noradrenergic and glutamatergic structures and pathways. PMID- 8348920 TI - Amyotrophic lateral sclerosis and frontal lobe dementia in Alzheimer's disease. Case report and review of the literature. AB - Clinicopathological data of a woman with a 3-year course of concurrent amyotrophic lateral sclerosis and dementia are presented. Dementia had occurred at time of onset of motor disturbances and presented as typical frontal lobe dementia. Pathology confirmed motor neuron disease of amyotrophic lateral sclerosis and frontal lobe atrophy. Multiple senile plaques were distributed cortically and in the hippocampus, where diffuse spread of neurofibrillary tangles was seen. Hence, this Alzheimer's dementia in a patient with sporadic amyotrophic lateral raises the question of a possible association between the two conditions. PMID- 8348919 TI - Botulinum toxin: preferred treatment for hemifacial spasm. AB - This paper retrospectively analyses the clinical data of 65 consecutive cases of hemifacial spasm. A benign etiology was clinically evident in the majority of cases. Neuroradiologic investigation ruled out serious intracranial pathology in atypical cases. Trials of oral medication in 26 patients were consistently unsuccessful. Fifty-one patients had repeated lid and facial muscle injections of botulinum toxin during a period of 8 years. The mean duration of effective relief from spasm following an initial treatment was 18.9 weeks. This effect did not diminish with repeated injections. PMID- 8348921 TI - Utilization behavior and concomitant motor neglect by bilateral frontal lobe damage. AB - We reported on a patient who had bilateral mesial frontal lesions, presumably of a primary cerebral malignant lymphoma. The patient presented with a combination of unusual behavioral disorders of the upper extremities, which has not yet been documented in the literature: bilateral utilization and imitation behaviors and motor neglect of the left arm. Utilization behavior was closely associated with bilateral manual grasping behavior and was caused by the bifrontal lesions. Damage to the right supplementary motor area resulted most likely in concomitant motor neglect of the left hand. Discussion includes differentiation from other related behavioral disorders. PMID- 8348922 TI - Kinesigenic dystonia as the first manifestation of multiple sclerosis with cervical and brainstem lesions. PMID- 8348923 TI - Pontine infarction with pure Millard-Gubler syndrome: precise localization with magnetic resonance imaging. PMID- 8348924 TI - Interrelationships between strains of Salmonella enteritidis. AB - In contrast to S. typhimurium [19], S. enteritidis is a serotype which has its primary food-animal reservoir in poultry. To date, phage typing has been of paramount importance in studying the epidemiology of this serotype and in particular, has demonstrated the involvement of both poultry meat and whole shell eggs in the transmission of S. enteritidis PT4 to humans. The findings discussed above describe various aspects of the serotype, particularly in relation to the involvement of both LPS and plasmids in its virulence and phage type identity (Fig. 2). These findings have led to an increased understanding of the biology of this serotype, which is of major importance in human food-poisoning in England and Wales at the present time. PMID- 8348925 TI - Levels of anti-pneumococcal antibodies in young children in Papua New Guinea. AB - Anti-pneumococcal polysaccharide antibody (anti-PPS) levels were measured in 153 serum samples collected from children aged between 2 and 47 months living in the highlands of Papua New Guinea (PNG). Fifty-seven of the samples were collected during acute episodes of lower respiratory tract infection (ALRI). Total IgA and IgG increased steadily with age; however, no association was found between the levels of these antibodies and the health status of the child. Total IgM levels showed little relationship to the age of the child but under 12 months of age levels were somewhat higher on average in children with pneumonia. For most of eight pneumococcal serotypes tested, specific IgG levels were found to decline rapidly in the first 6-8 months, reaching a minimum at approximately 12 months of age. Serotype 3 was exceptional in having very low titres in the youngest children. A separate analysis of 24 cord sera suggested that antibodies to this serotype do not usually cross the placenta in PNG. Children with pneumonia tended to have lower levels of specific IgG than healthy controls of the same age. Specific anti-PPS IgA levels were found to increase steadily with age, but were not associated with health status. PMID- 8348926 TI - Factors associated with Paracoccidiodes brasiliensis infection among permanent residents of three endemic areas in Colombia. AB - The natural habitat of Paracoccidioides brasiliensis, the aetiologic agent of paracoccidioidomycosis, has not been determined. Consequently, the events leading to the acquisition of infection remain controversial. To identify factors associated with infection in endemic areas we conducted a survey in three rural communities in Colombia where we had previously diagnosed paracoccidioidomycosis in children. Permanent residents were surveyed taking into consideration environmental and occupational variables. Skin tests were used to classify subjects as infected or non-infected. Variables found associated with infection were: (i) community A: previous residence around Porce river and agriculture in vegetable gardens; (ii) community C: frequent use of specific water sources; (iii) community V: housekeeping activities, and (iv) total group: age > 25 years and contact with bats. Residents in communities with higher prevalence of infection were older, had more complex residence history, and referred more contact with armadillos than residents of communities with lower infection. PMID- 8348927 TI - The haemagglutinins of influenza A (H1N1) viruses in the 'O' or 'D' phases exhibit biological and antigenic differences. AB - Influenza A (H1N1) viruses when initially isolated in mammalian cell cultures (MDCK cells) had different agglutination reactions with chicken and guinea-pig erythrocytes compared to the same viruses after passage. On first isolation the virus HA resembled the 'O' phase viruses described originally by Burnet and Bull and agglutinated mammalian but not avian erythrocytes. After passage, the virus HA resembled a classical 'D' phase virus and agglutinated both avian and mammalian erythrocytes. Monoclonal and polyclonal antisera detected antigenic differences between the HAs of the viruses in the 'O' and 'D' phases. The 'O' phase virus HA reacted preferentially with antibodies in post infection human antisera. Viruses in the 'O' phase replicated poorly in the allantoic cavity of embryonated hens' eggs whilst 'D' phase virus replicated in both MDCK cells and in embryonated hens' eggs. At least three distinguishable subpopulations of influenza A (H1N1) viruses may co-exist in clinical throat swab material, including viruses possessing HAs in the 'O' and 'D' phases and other 'D' phase viruses cultivable in embryonated hens' eggs but antigenically distinguishable from the corresponding 'D' phase virus in MDCK cells. PMID- 8348928 TI - Dengue epidemic in the stage of Rio de Janeiro, Brazil, 1990-1: co-circulation of dengue 1 and dengue 2 serotypes. AB - During 1990 and 1991, dengue fever was detected in the State of Rio de Janeiro, Brazil. It occurred in two epidemic waves; one, from January to August 1990, caused predominantly by dengue virus type 1 (DEN-1) the other from October 1990 to May 1991 caused by type 2 virus (DEN-2). Dengue was confirmed by virus isolation and/or IgM capture enzyme-linked immunosorbent assay (MAC-ELISA) in 2109/5964 (35.4%) of the cases. DEN-2 virus was isolated from 180 patients. HAI tests indicated that of these previous infection with DEN-1 had occurred in 130 (72%). The epidemic was classified as dengue fever, but severe and even fatal cases occurred in association with secondary infection. PMID- 8348929 TI - Protective efficacy of BCG vaccine against leprosy in southern Malawi. AB - This paper describes a matched case-control study to determine the efficacy of BCG vaccine in preventing the occurrence of leprosy in southern Malawi, a previously unstudied area. The BCG immunization rate amongst 145 individuals with leprosy was 44.8%, compared to 62.5% in 290 matched controls. The protective efficacy of BCG vaccine against leprosy in this region was estimated to be 63.6%; smallpox immunization had no effect. These findings support the view that BCG vaccine should be considered as a control measure in areas where leprosy is endemic. PMID- 8348930 TI - Acquisition and invasiveness of different serotypes of Streptococcus pneumoniae in young children. AB - Rates of acquisition and mean duration of nasal carriage of different serotypes of Streptococcus pneumoniae have been estimated by fitting a stochastic model to longitudinal carriage data in children from Papua New Guinea. Immunogenicity and two indices of relative invasiveness were determined for each serotype. Immunogenic serotypes were less frequently acquired and were carried for shorter periods, but no relationship between immunogenicity and invasiveness was apparent using either index of invasiveness. Frequent invasion was associated with a high acquisition rate and high frequency and prolonged duration of carriage. Carriage studies can provide a broad indication of which serotypes cause invasive disease but not the proportion of disease due to individual serotypes; some serotypes which cause invasive disease (e.g. serotype 46) are not found even in extensive carriage studies. The antibiotic resistance of carriage organisms, however, does approximate the resistance patterns of invasive organisms and thus may be used to monitor changing patterns of antimicrobial susceptibility in the community. PMID- 8348931 TI - Age-specific efficacy of pertussis vaccine during epidemic and non-epidemic periods. AB - A national survey was conducted of 3150 notified cases of whooping cough in order to determine age-specific pertussis vaccine efficacy by the 'screening' method. The cases were collected over two periods, one just prior to the start and one at the first peak of the whooping cough epidemic of 1989-90. Vaccination status was determined by a postal questionnaire to the reporting doctor and clinical data were also collected to provide efficacy estimates according to standardized case definitions. Overall, observed vaccine efficacy was high but differed between epidemic (87%) and non-epidemic (93%) periods (P = 0.03). Efficacy estimates were generally higher for typical or severe cases than for children with an atypical illness. Vaccine efficacy declined with age (P < 0.01) but estimates remained high up to the age of 8 years. This study will provide baseline data for comparison with efficacy observed from similar studies of children immunized at an accelerated schedule and from phase III studies of acellular pertussis vaccines performed elsewhere. PMID- 8348932 TI - High prevalence of thermostable direct hemolysin (TDH)-like toxin in Vibrio mimicus strains isolated from diarrhoeal patients. AB - A total of 17 isolates of Vibrio mimicus from patients, 29 from environment and 2 from food was examined for toxigenicity. Sixteen (94%) clinical isolates and one (50%) from food produced TDH-like toxin, whereas none of the environmental isolates did so. The food from which V. mimicus with TDH-like toxin production was isolated, was one which had caused food poisoning. Only one environmental strain produced CT-like toxin, whilst ST-like toxin was not detected from any strains tested. PMID- 8348933 TI - Outbreak of nosocomial infections with two different MRSA-strains involved: significance of genomic DNA fragment patterns in strains otherwise difficult to type. AB - Methicillin-resistant Staphylococcus aureus isolates from an outbreak of 17 cases of wound infection in a municipal hospital were typed by conventional methods, phage typing by three sets of phages, reverse phage typing and plasmid profiles, as well as by genomic DNA fragment patterns obtained after Sma-I digestion and pulsed-field electrophoresis. These isolates were non-typable by phages, only some were typable by reverse phage typing and were not uniform in plasmid profile. Only the genomic DNA fragment patterns resulted in a clear discrimination of 2 strains (12 isolates for the first and 7 isolates for the second). Both strains were disseminated in different wards of the same hospital and one strain had obviously spread to another clinic in the same city. PMID- 8348934 TI - Social and geographical risk factors in Helicobacter pylori infection. AB - A correlation between childhood crowding and the later development of gastric cancer has been demonstrated by Barker and colleagues, who proposed that the relationship was the consequence of infection by an organism such as Helicobacter pylori. In order to test this hypothesis the presence of IgG antibodies to H. pylori in sera from blood donors in North Wales has been investigated. During donation sessions, donors answered questions relating to social conditions and domicile in childhood (at age 10 years) and adult life (the preceding 2 years). A stepwise logistic regression analysis of the data demonstrated significant independent relationships between seropositivity and the following factors: sharing a bed in childhood, housing density, locality of birth, adult social class and age. PMID- 8348935 TI - A miniaturized biotyping system for strain discrimination in Escherichia coli. AB - A two-tier miniaturized scheme of eight tests was devised for biotyping strains of Escherichia coli in microwell plates. Primary biotypes were defined by positive and negative reactions in tests for fermentation of raffinose, sorbose, dulcitol and 2-deoxy-D-ribose and for decarboxylation of ornithine when read after specified periods of incubation; subtypes were identified within primary biotypes according to results in secondary tests for rhamnose fermentation, lysine decarboxylation and motility. The method gave reproducible results on different occasions of testing. Among 100 E. coli strains from various sources, 26 of the 32 possible primary biotypes and 56 full biotypes, as defined by results in both primary and secondary tests, were identified, thus demonstrating a high index of strain discrimination (D = 0.98). The scheme is recommended as a simple, reliable, inexpensive and efficient method of differentiating strains of E. coli. PMID- 8348937 TI - Mycobacterium bovis in the European badger (Meles meles): epidemiological findings in tuberculous badgers from a naturally infected population. AB - This study investigates the course of tuberculosis in a naturally infected badger population, its impact on the population and the risk of spread to other species in the light of capture data and post-mortem findings from 47 tuberculous badgers, stratified by age group and sex, accrued since 1975. The findings are compared with those for 260 badgers from the same population in whom no evidence of infection was detected. Detailed estimates of seasonal variations in bodyweight for uninfected male and female cub, yearling and adult badgers are presented and compared to the weights at post-mortem examination of the tuberculous badgers, in whom poor condition and weight loss were the principal presenting signs. Lesions were seen especially in the lungs and associated lymph nodes, and in the kidneys. Organisms were detected intermittently in faeces, urine, sputum and discharging bite wounds. Infected animals could survive for nearly 2 years and produce cubs successfully. PMID- 8348936 TI - An analysis of the diversity of Haemophilus parainfluenzae in the adult human respiratory tract by genomic DNA fingerprinting. AB - A method for typing Haemophilus species is described, based on the analysis of genomic DNA from Haemophilus parainfluenzae. The DNA was extracted by a rapid method and digested with the restriction enzyme BamHI to provide a characteristic 'fingerprint'. The pattern of fragments in the ranges 1-1.6 kb, 1.6-2 kb and 2-3 kb were used to produce a numerical profile of each isolate. In total 97 isolates were examined; 88 from throat swab material isolated from the 15 members of a British Antarctic Survey base and 9 type strains. Seventy-two of the 88 antarctic isolates were H. parainfluenzae and were found to be very diverse, comprising 41 identifiable strains with up to 5 strains being isolated from a single throat swab sample. There was evidence for both carriage and transmission within the isolated community. The technique provided a highly discriminatory method for characterizing Haemophilus strains which is suitable for epidemiological studies. PMID- 8348938 TI - Management of graft-versus-host disease. PMID- 8348939 TI - In vitro inhibition of interleukin-2-induced defective polymorphonuclear chemotaxis by TNF inhibitor. AB - Patients undergoing immunotherapy with interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed that a profound deficiency of neutrophil chemotaxis is induced by interleukin-2 therapy. Migration in response to N-formyl-methionyl-leucyl phenylalanine (FMLP), being normal before therapy, was markedly impaired after the first cycle and further decreased after the third cycle of treatment. A direct effect of interleukin-2 on neutrophil chemotaxis is controversial. However, peripheral blood cells exposed to interleukin-2 secrete secondary cytokines. In particular, the release of tumor necrosis factor after interleukin 2 injection has been proposed as an important regulatory mechanisms. When testing random migration and chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients, we found that this serum induced a defective chemotaxis similar to that of neutrophils from interleukin-2-treated patients. In order to assess the influence of tumor necrosis factor, we tested the effect of anti-tumor necrosis factor-alpha antibody on the chemotactic response of cells after incubation with the serum, and we observed a dose dependent reduction of neutrophil chemotaxis deficiency. These data suggest that TNF is counteracting the neutrophil chemotactic deficiency observed during IL-2 treatment. PMID- 8348940 TI - High-dose cyclophosphamide, etoposide and BCNU (CVB) with autologous stem cell rescue in malignant lymphomas. AB - Eighteen patients with malignant lymphoma, 10 non-Hodgkin's and 8 Hodgkin's, were treated with high-dose CVB (cyclophosphamide 4 x 1.5 g/m2, etoposide 4 x 250-400 mg/m2, carmustine 4 x 150-200 mg/m2), followed by autologous peripheral blood stem cells (PBSC, 13 patients) or bone marrow (BM, 5 patients) transplantation. At the time of autograft 6 patients were in complete remission (CR), 3 in partial remission (PR) and 5 in relapse (4 sensitive, 1 resistant), whereas 4 had progressive disease. All CR patients had poor prognostic features at presentation. PBSC were collected at the time of rapid hematologic recovery after intense chemotherapy by means of a cell separator. All patients engrafted. Median time to achieve > or = 0.5 x 10(9)/l polymorphonuclear cells (PMN) and > or = 50 x 10(9)/l platelets was 13 days for both cell types in PBSC autografted patients, versus 20 and 28 days respectively in BM autografted patients. A significant advantage of PBSC over BM was found in terms of time needed to recover either PMN > or = 0.5 and PMN > or = 1 x 10(9)/l (p = 0.01). Autograft-related toxicity consisted mainly of moderate severity interstitial pneumopathy (3 patients), and veno-occlusive disease (1 patient) that resolved completely. Of the 12 patients autografted with detectable disease, 6 (50%) obtained a CR. Seven out of 18 autografted patients (39%) had disease progression within 1 to 5 months of autograft. The projected progression-free survival is over 50% at 4 years and it was significantly longer in patients with sensitive disease than in those with resistant disease (p = 0.01). The efficacy and the low toxicity of CVB suggest that autograft with PBSC may be proposed for the primary treatment of poor prognosis malignant lymphomas. PMID- 8348941 TI - Cobalamin absorption and serum homocysteine and methylmalonic acid in elderly subjects with low serum cobalamin. AB - We prospectively studied 41 consecutive elderly patients with serum cobalamin (vitamin B12) levels lower than 125 pmol/l. The protein-bound cobalamin absorption test (PBAT) was performed in 34 of them and in 27 selected elderly control patients. The lower decision limit was 0.18% and an abnormal test was detected in only 9 (26%) of the 34 patients with low serum cobalamin level. When the PBAT was compared to the Schilling (Dicopac method) test, a concordant result was found in 80%. Serum methylmalonic acid and/or total homocysteine concentrations were elevated in 75% (26/35) of the patients with low serum cobalamin levels but also in 30% (5/17) of the control patients. Of the 12 and 9 cobalamin-deficient patients with elevated serum levels of methylmalonic acid and homocysteine, normalization after cobalamin therapy was obtained in 11 and 5 respectively. In conclusion, determination of serum metabolites and their response to cobalamin therapy are a sensitive index of significant cobalamin deficiency and a useful means of distinguishing between cobalamin and folate deficiency. The PBAT offers little advantage over the Schilling test in diagnosing cobalamin malabsorption in elderly patients. PMID- 8348942 TI - Quantitative and qualitative studies of red cell ferritin in refractory anemia of myelodysplastic syndrome. AB - The red cell ferritin (rFt) level in 10 patients with refractory anemia (RA) was measured and analyzed by column isoelectric focusing (IEF). The levels in 9 of the 10 patients (90.0%) were higher than the upper limit in healthy controls (MV +/- SD: male 14.3 +/- 10.3 ag/cell, female 7.5 +/- 3.6 ag/cell). The isoelectric point (pI) of rFt determined by IEF in healthy subjects ranged from 5.1 to 5.7. However, the pI ranges for RA patients varied widely; the pI value was thought to correlate with the severity of the morphological abnormalities of bone marrow (BM) erythroblasts. That is, the greater the proportion of morphologically abnormal erythroblasts with respect to all erythroid precursors, the lower the pI range for rFt. The rFt content was not related to serum iron, transferrin saturation, serum ferritin, reticulocyte count, red cell iron content, or BM erythroblast count. These data suggest that rFt synthesis in RA patients is influenced by factor(s) other than iron; this is considered an essential feature of erythropoiesis in myelodysplastic syndrome (MDS). PMID- 8348943 TI - Two new candidate mutations in type IIA von Willebrand's disease (Arg834-->Gly, Gly846-->Arg) and one polymorphism (Tyr821-->Cys) in the A2 region of the von Willebrand factor. AB - Recently, several von Willebrand factor gene mutations resulting in type IIA von Willebrand's disease have been reported. We examined 8 patients from Sweden and Denmark with this phenotype and found two new candidate mutations and a hitherto unknown amino acid polymorphism. One patient had a de novo occurring mutation resulting in substitution of glycine for arginine 834. Previous reports have demonstrated conversion of arginine 834 to tryptophan or glutamine in IIA patients. A 2nd patient had a G(4825)-->A transition, substituting arginine for glycine 846. The transition produces a sequence congruent with that of the pseudogene but several lines of evidence indicate that a sequencing error due to influence by the latter could be excluded. The remaining 6 patients had one of the earlier described substitution mutations: Ser743-->Leu and Ile865-->Thr. In addition, two sequence variations not linked to the phenotype were found, namely Tyr821-->Cys and Val802-->Leu. PMID- 8348945 TI - Philadelphia chromosome-positive chronic myelocytic leukemia with abnormal chromatin clumping (ACC) syndrome. PMID- 8348944 TI - Etoposide, doxorubicin, cyclophosphamide and high-dose betamethasone (EACB) as outpatient salvage therapy for refractory multiple myeloma. AB - Fifty-six patients with refractory multiple myeloma were treated with intermittent courses of etoposide, doxorubicin, cyclophosphamide and high-dose betamethasone (EACB) every 4th week. The overall response rate was 30%. Durable remissions exceeding 1 year were obtained in 12 of the 17 responding patients. A significant prolongation of the survival time was found for responding patients (median 13 months) compared to those patients who did not respond (median 9 months) to EACB therapy (p = 0.01). A low frequency of neutropenic fever episodes was noted compared to other salvage treatment regimens. The EACB regimen was usually well tolerated and could be administered safely on an out-patient basis. This regimen might be an alternative especially for elderly patients unresponsive to initial therapy. PMID- 8348946 TI - Bone-marrow biopsy of the iliac bone followed by severe retroperitoneal hemorrhage. PMID- 8348947 TI - Haem administration in myelodysplastic syndromes: a possible mechanism of action. PMID- 8348948 TI - Repeated continuous administration of low doses of intravenous iron in anemic patients with active rheumatoid arthritis. PMID- 8348949 TI - Increase in number of bone marrow macrophages in patients with myelodysplastic syndromes. PMID- 8348950 TI - Rise in heat-shock protein level confers tolerance to energy deprivation. AB - Heat shock (44 degrees C for 10 min) or ATP depletion by an uncoupler (CCCP for 20 min) is shown to result in stimulation of hsp68/70 synthesis in Ehrlich tumor cells. After 3 h of recovery, the cells become thermotolerant. Surprisingly, repeated ATP depletion caused by CCCP or rotenone (a respiratory inhibitor) treatment, had a much lower effect on cell viability. Both induction of tolerance to energy deprivation and hsp68/70 synthesis were totally suppressed by cycloheximide, an inhibitor of cytosolic protein synthesis. In tolerant cells, rotenone still induced ATP depletion; however, protein aggregation (the rise in Triton-insoluble proteins) was inhibited in these cells. It is suggested that cellular chaperones (e.g. hsp70) are involved in the protection of ischemic cells from necrosis, preventing protein aggregation under ATP deficiency. PMID- 8348951 TI - Molecular cloning and sequencing of the cDNA coding for a calcium-binding protein regucalcin from rat liver. AB - The cDNA of a Ca(2+)-binding protein regucalcin was cloned from a rat liver cDNA library which was constructed in lambda ZAPII by immunoscreening. Positive clones were obtained from which spanned the region of interest, and they gave a sequence of 1.7 kb by sequencing with the dideoxynucleotide method. Analysis of the sequence of the cloned cDNA showed that the cDNA encoded the complete amino acid sequence of the regucalcin molecule. Regucalcin was composed of 299 amino acid residues and its molecular weight was estimated to be 33,388 Da. The hydropathy profile of regucalcin showed a highly hydrophilic character. The nucleotide and amino acid sequences of regucalcin did not have statistically significant homology, as compared with the registered sequences which are found in the EMBL and GenBank databases containing several other Ca(2+)-binding proteins (calmodulin, calbindin-D28k and S-100 beta). The regucalcin molecule did not contain the EF-hand motif as a Ca(2+)-binding domain. The present study demonstrates that regucalcin is a unique Ca(2+)-binding protein in the liver of rats. PMID- 8348952 TI - Structure and dynamics of bacteriorhodopsin. Comparison of simulation and experiment. AB - Global features of the structure and dynamics of bacteriorhodopsin are investigated using molecular modelling, dynamical simulations and neutron scattering experiments. The simulations are performed on a model system consisting of one protein molecule plus intrinsic water molecules. The simulation derived structure is compared with neutron diffraction data on the location of water and with the available electron microscopy structure of highest resolution. The simulated water geometry is in good accord with the neutron data. The protein structure deviates slightly but significantly from the experiment. The low frequency vibrational frequency distribution of a low-hydration purple membrane is derived from inelastic neutron scattering data and compared with the corresponding simulation-derived quantity. PMID- 8348953 TI - Penetration of oligonucleotides into mouse organism through mucosa and skin. AB - Benzylamide 5'-32P-oligonucleotide derivatives were shown to penetrate into mice organism when administered by various routes; intranasally, per os, intravaginally and per rectum. In all cases, the compounds are rapidly accumulated in blood and guts. Analysis of the radioactive material from blood and pancreas revealed intact oligonucleotides. Although concentrations of oligonucleotides in tissues differ considerably by the various methods of administration, the efficiency of delivery is sufficient to consider all the routes as being of therapeutic value. Dose effect on the efficiency of oligonucleotide penetration into mice suggests the transport to be a saturable process. Application of an oligonucleotide lotion on mice ear helices results in reproducible accumulation of radioactivity in the animal tissues. Effectiveness of oligonucleotide delivery into mouse through skin can be improved by using electrophoretic procedure. PMID- 8348954 TI - Cyanide-reactive sites in cytochrome bd complex from E. coli. AB - Cyanide reacts with cytochrome bd from E. coli in an 'aerobically oxidized' state (mainly, an oxygenated complex b558(3+) b595(3+) d(2+)-O2), bringing about (i) decomposition of the heme d2+ oxycomplex (decay of the 648 nm absorption band) and (ii) extensive red shift in the Soret region accompanied by minor changes in the visible range assigned to ferric heme b595. MCD spectra show that the Soret red shift is associated with heme b595(3+) high-to low-spin transition. This is the first unambiguous demonstration that heme b595 can bind exogenous ligands. No reaction of cyanide with b558 is observed. In about 70% of the enzyme which forms the cyano complex, the spin-state transition of b595 decay of heme d oxycomplex match each other kinetically (keff ca. 0.002 s-1 at 50 mM KCN, pH 8.1, 25 degrees C). This points to an interaction between the two hemes. The concerted binding of cyanide to d3+ and b595(3+), perhaps as a bridging ligand, is probably rate limited by d2+ oxycomplex autoxidation. In the remaining 30% of the isolated bd, there is a rapid phase of cyanide-induced b595 spin-state transition which can be tentatively assigned to that proportion of the enzyme in which heme d is initially in the ferric rather than ferrous-oxy form. PMID- 8348955 TI - Agonist pharmacology of the neuronal alpha 7 nicotinic receptor expressed in Xenopus oocytes. AB - The potencies and efficacies of seven agonists at chick alpha 7 nicotinic receptors expressed in Xenopus oocytes were determined by whole cell recording. (+)-Anatoxin-a was the most potent agonist (EC50 = 0.58 microM) and acetylcholine was the least potent (EC50 = 320 microM). The rank order of agonist potencies was: (+)-anatoxin-a >> cytisine > (-)-nicotine > (+)-nicotine > DMPP > 1-acetyl-4 methylpiperazine methiodide > acetylcholine. DMPP evoked only very small currents: comparison of maximally effective agonist concentrations showed that DMPP was only one-fifth as efficacious as other agonists. Previously published IC50 values for rat brain [125I]alpha-bungarotoxin sites show a similar agonist profile, and the identity of homo-oligomeric alpha 7 receptors with native alpha bungarotoxin-sensitive neuronal nicotinic receptors is discussed. PMID- 8348956 TI - A gene homologous to the reg gene is expressed in the human pancreas. AB - We have determined the nucleotide sequence of regl a human genomic DNA fragment homologous to the reg gene which is expressed in the exocrine pancreas and regenerating islets. Sequence comparisons of reg and regl suggested similar exon intron organisation. Based on this assumption, specific oligonucleotides for regl exons were used to demonstrate expression of the regl gene in pancreas and liver. The proteins encoded by reg and regl comprise 166 amino acids and differ by 22 amino acids only. PMID- 8348957 TI - Mature carnitine palmitoyltransferase I retains the N-terminus of the nascent protein in rat liver. AB - Carnitine palmitoyltransferase I was isolated from octylglucoside extracts of rat liver mitochondrial outer membranes. This native enzyme was digested proteolytically with V8 protease. Five major peptides were obtained all of which were found in the amino acid sequence predicted from the full-length cDNA sequence of the protein. One peptide was found to correspond to the extreme N terminus of the deduced amino acid sequence. Therefore, the mature protein retains the N-terminus of the nascent protein after import into the mitochondrial membrane. Knowledge of the identity of the N-terminus of the mature protein allows a reappraisal of the role of the two main. N-terminal hydrophobic domains of the protein and of the possible topology of the protein within the membrane. PMID- 8348958 TI - Stimulation-induced expression of slow muscle myosin in a fast muscle of the rat. Evidence of an unrestricted adaptive capacity. AB - Fast muscles of the rat hind limb were stimulated continuously at 10 or 20 Hz for periods of 55-61 days by means of an implantable neuromuscular stimulator. Gel electrophoresis clearly demonstrated the presence in stimulated muscles of slow myosin light and heavy chains, although fast isoforms were still present in all cases. Thus, contrary to previous reports, induction of slow myosin isoforms does occur in this, as in other, mammalian species. The time course of the response to stimulation appears to be more extended than that seen in the rabbit. PMID- 8348960 TI - Purification of a novel factor which binds to the mouse alpha 2 (I) collagen promoter. AB - We have identified and purified a DNA binding protein which specifically binds to a segment of the mouse alpha 2 (I) collagen promoter between -420 and -399 bp upstream of the start of transcription. Purification included heparin-agarose and sequence-specific DNA-affinity chromatography, followed by SDS-PAGE and renaturation of the DNA binding activity after elution from SDS-polyacrylamide gel. The DNA binding activity resides in two species of 42 kDa and 40 kDa, respectively. The levels of DNA binding activity of this factor, which has been tentatively designated as ColF1, are considerably higher in nuclear extracts of NIH-3T3 fibroblasts than in nuclear extracts from epidermal cells, lymphoid cells and transformed NIH-3T3 fibroblasts. PMID- 8348961 TI - Reduced content of the quinone acceptor QA in photosystem II complexes isolated from thylakoid membranes after prolonged photoinhibition under anaerobic conditions. AB - The plastoquinone content of photosystem II complexes isolated from spinach photosystem II-enriched membranes subjected to strong photoinhibitory illumination under anaerobic conditions was determined by HPLC. A pronounced decrease of the plastoquinone content was found in the photoinactivated complexes. These results corroborate earlier models in which photoinhibitory illumination is suggested to eventually lead to release of doubly reduced and protonated QA from its site on the D2-protein. PMID- 8348959 TI - TRP-1 expression correlates with eumelanogenesis in human pigment cells in culture. AB - We have investigated the relationship in human cultured normal and malignant melanocytes between the accumulation of mRNAs encoding tyrosinase and tyrosinase related protein-1 (TRP-1), the activity of tyrosinase and the presence of melanin. Tyrosinase mRNA correlates with tyrosinase activity and with the presence of pheomelanin, eumelanin or both melanin types. In contrast TRP-1 mRNA is only detectable in cells containing eumelanin, which suggests a role for TRP-1 in the eumelanin synthesis pathway. PMID- 8348962 TI - Kinetics of CO binding to putative Na(+)-motive oxidases of the o-type from Bacillus FTU and of the d-type from Escherichia coli. AB - The kinetics of CO reassociation with isolated Bacillus FTU o-type oxidase and with solubilized membranes of Escherichia coli (GO102 strain) containing the d type oxidase only, upon laser flash photolysis under reducing conditions, were studied. In both cases, kinetics are shown to be composed of three phases (tau 35 70 microseconds, 0.25-0.5 ms and 2-5 ms). The spectra of the flash-induced absorbance changes of the first kinetic components proved to be characteristic of CO-o- and CO-b595 d-cytochrome complexes in Bac. FTU and E. coli, respectively. The spectra of the second and the third components appeared to be nearly the same in Bac. FTU and E. coli with peaks for the former at 436-437 and 590 nm and troughs at 419-420 and 569 nm; and for the latter with peaks at 436-437 and 558 560 nm and troughs at 419-420 and 575-578 nm. The similarity between the putative Na(+)-pumping Bac. FTU o- and E. coli d-type oxidases and their difference from the H(+)-motive Bac. FTU caa3- and E. coli o-type oxidases are discussed. PMID- 8348963 TI - Kinetics of CO binding to H(+)-motive oxidases of the caa3-type from Bacillus FTU and of the o-type from Escherichia coli. AB - The kinetics of CO rebinding with isolated Bacillus FTU caa3-type oxidase and with solubilized Escherichia coli membranes (GO103 strain) containing the o-type oxidase as the main O2-reducing enzyme were studied under reducing conditions by laser flash photolysis of the CO-oxidase complexes. The spectra of the optical absorbance changes upon photolysis were characteristic of CO-caa3- and CO-o oxidase complexes in Bac. FTU and E. coli, respectively. Small quantities of d type oxidase in E. coli GO103 membranes were detected. The kinetics of CO reassociation with reduced caa3- and o-type oxidases were monophasic with tau 25 30 ms in both cases. PMID- 8348964 TI - Model peptides to study the effects of P2 and P3 substitutions in statine containing HIV proteinase inhibitors. AB - Through a series of synthetic model peptides, we have examined the structural requirements of the P2 and P3 residues in statine-based HIV protease (PR) inhibitors. Results agree with the general observations that, the more bulky the P3 aromatic hydrophobic side chain, the more potent is the inhibitor. At P2, an isopropyl side chain is critical in maintaining potency. Three-dimensional modeling demonstrates that the steric bulk of a leucyl residue or the unfavorable energy transfer, from water to enzyme, for a basic amino acid residue at P2 markedly compromises activity. A naphthylalaninyl-valyl P3-P2 substituted analogue inhibits PR with an IC50 value of 6 nM, and was also effective as an antiviral agent. PMID- 8348965 TI - Crystal structure of apo-glycolate oxidase. AB - The crystal structure of the apoform of the alpha/beta-barrel enzyme glycolate oxidase has been determined to 2.6 A resolution. Removal of the tightly bound cofactor FMN has a very strong influence on the protein structure; it is converted into a very flexible state, verging on a molten globule type of structure. The asymmetric unit contains two subunits with different conformations to each other and to the holo-enzyme. The secondary structures are preserved, but their mutual arrangement has changed to some extent introducing cavities into the protein. The largest structural shifts are, however, found in the loops. PMID- 8348966 TI - Identification of a putative active site residue in the exo-beta-(1,3)-glucanase of Candida albicans. AB - Recombinant exo-beta-(1,3)-glucanase from Candida albicans was expressed in Saccharomyces cerevisiae and purified. The enzyme contains a number of short blocks of sequence homology with several genes for cellulases of the family A glucanases including the conserved sequence motif NEP which has previously been shown to be important in the catalytic function of several cellulases. Site directed mutagenesis of this glutamic acid residue in the 1,3 glucanase (E230D, E230Q) decreased the enzymatic activity 15,000- and 400-fold, respectively. This suggests that the E of the NEP participates in catalysis of the exoglucanase and other related glucanases. PMID- 8348967 TI - Enzymatic catalysis as a process controlled by protein conformational relaxation. AB - Great progress in studies of protein dynamics in the past decade propels an essential alteration in our understanding of the enzymatic catalysis phenomenon. A careful analysis of assumptions made by the hitherto used conventional theory of chemical reactions shows that neither of them is in fact satisfied. One of the reasons is the presence of a slow interconformational dynamics within the protein native state. In consequence, the simple classical statement "enzymes accelerate reactions by decreasing the free energy of activation" represents only half of the truth. Enzymatic reactions actually proceed through 'gates' of relatively low free energy but it is not the process of activated gate crossing that limits the reaction rate, but the process of generally non-activated gate opening, controlled by the conformational relaxation. Possible consequences of this fact are pointed out. PMID- 8348968 TI - Rapid alteration of c-myc and c-jun expression in leukemic cells induced to differentiate by a butyric acid prodrug. AB - The novel prodrug of butyric acid (BA), pivaloyloxymethyl butyrate, has been shown, in vitro, to induce differentiation and inhibit leukemic cell proliferation. The prodrug affects the cells in vitro at lower concentration and at least 100 times faster than does (BA). We have compared the ability of BA with that of its prodrug AN-9 to modulate the expression of the early regulating genes, c-myc and c-jun, in HL-60 cells. Exposure of HL-60 cells to the prodrug resulted in a decrease of c-myc and an increase of c-jun expression. The prodrug elicited this effect at lower concentrations and at least 100 times faster than BA. Since changes in the expression of c-myc and c-jun occur minutes after exposure of the cells to the prodrug, these genes are likely to play a major role in the early stages of the differentiation pathway. PMID- 8348970 TI - Cephalopod alcohol dehydrogenase: purification and enzymatic characterization. AB - Octopus, squid and cuttle-fish organs were examined for alcohol dehydrogenase activity. Only one form was detectable, with properties typical of mammalian class III alcohol dehydrogenase. The corresponding protein was purified from octopus and enzymatically characterized. Ion-exchange and affinity chromatography produced a pure protein in excellent yield (73%) after 1600-fold purification. Enzymatic parameters with several substrates were similar to those for the human class III alcohol dehydrogenase, demonstrating a largely conserved function of the enzyme through wide lines of divergence covering vertebrates, cephalopods and bacteria. The results establish the universal occurrence of class III alcohol dehydrogenase and its strictly conserved functional properties in separate living forms. The absence of other alcohol dehydrogenases in cephalopods is compatible with the emergence of the ethanol-active class I type at a later stage, in lineages leading to vertebrates. PMID- 8348969 TI - Cytoplasmic triacylglycerols and cholesteryl esters are degraded in two separate catabolic pools in cultured human fibroblasts. AB - The sources and the catabolic pathways of cytoplasmic pools of triacylglycerols and cholesteryl esters have been comparatively investigated in cultured fibroblasts from normal subjects and from patients affected with neutral lipid storage disease (NLSD) and Wolman disease (WD). (i) Endogenously biosynthesized triacylglycerols and cholesteryl esters were degraded extra-lysosomally since they were catabolized at similar rates in normal and in WD fibroblasts. In NLSD fibroblasts, the degradation of endogenous triacylglycerols was severely deficient, whereas that of endogenous cholesteryl esters was in the normal range. (ii) Reconstituted high density lipoproteins (HDL) containing radiolabelled [3H]triolein and cholesteryl [14C]oleate were taken up by cultured fibroblasts and rapidly degraded in a non-lysosomal compartment. In NLSD fibroblasts the degradation of HDL-[3H]triolein was blocked whereas that of HDL-[14C]cholesteryl oleate was in the normal range. These data suggest that: (i) the cytoplasmic pools of triacylglycerols and cholesteryl esters originate from HDL uptake and from endogenous biosynthesis as well; (ii) cytoplasmic (non-lysosomal) triacylglycerols and cholesteryl esters are degraded by two separate catabolic pathways. PMID- 8348971 TI - Identification of a second membrane-active 13-residue peptide segment in the antimicrobial protein, bovine seminalplasmin. AB - Seminalplasmin (SPLN) is a 47-residue protein from bovine seminalplasma having broad-spectrum antibacterial activity. The protein has no hemolytic activity. SPLN interacts with lipid vesicles and its antibacterial activity appears to stem from its ability to permeabilize the bacterial plasma membrane. Analysis of SPLN's primary structure, with respect to its relative hydrophobicity and hydrophilicity, revealed a segment, PKLLETFLSKWIG, more hydrophobic than the rest of the protein. A synthetic peptide corresponding to this region had not only antibacterial activity but also hemolytic properties. Analysis of the SPLN sequence based on hydrophobic moment plots has revealed a second segment, SLSRYAKLANRLA, which could be membrane active. A synthetic peptide corresponding to this region shows only antibacterial activity with no hemolytic activity. PMID- 8348972 TI - Cis-acting elements in the promoter region of the human aldolase C gene. AB - We investigated the cis-acting sequences involved in the expression of the human aldolase C gene by transient transfections into human neuroblastoma cells (SKNBE). We demonstrate that 420 bp of the 5'-flanking DNA direct at high efficiency the transcription of the CAT reporter gene. A deletion between -420 bp and -164 bp causes a 60% decrease of CAT activity. Gel shift and DNase I footprinting analyses revealed four protected elements: A, B, C and D. Competition analyses indicate that Sp1 or factors sharing a similar sequence specificity bind to elements A and B, but not to elements C and D. Sequence analysis shows a half palindromic ERE motif (GGTCA), in elements B and D. Region D binds a transactivating factor which appears also essential to stabilize the initiation complex. PMID- 8348973 TI - Endotoxin induces rat lung ribonuclease activity. AB - Lipopolysaccharide (endotoxin), a component of Gram-negative bacteria, causes marked alterations in eukaryotic gene expression and cellular physiology. We show that within one hour of injection of endotoxin into adult rats there is an induction of ribonuclease activity in the lung. The degradation of RNA was prevented by treatment of the lung extract from endotoxin-injected rats with ribonuclease inhibitor (RNasin). We suggest that induction by endotoxin of ribonuclease activity is a novel mechanism by which cells could alter gene expression to meet an environmental challenge and caution that the presence of ribonuclease can hinder molecular biological analyses of tissue extracts from endotoxin-treated rats. PMID- 8348974 TI - Novel surface functional properties of polymannosyl lysozyme constructed by genetic modification. AB - The surface functional properties of glycosylated lysozyme were investigated by using polymannosyl and oligomannosyl enzymes at the position 49 by genetic modification [Nakamura, S. et al. (1993) J. Biol. Chem. 268, in press]. The polymannosyl lysozyme exhibited excellent emulsifying properties superior to those of commercial emulsifiers in addition to heat stability, while the oligomannosyl lysozyme did not. The surface tension of the polymannosyl lysozyme was greatly decreased correspondingly to the enhanced emulsifying properties, although that of oligomannosyl protein was not. The emulsifying activity and the emulsion stability of the polymannosyl lysozyme were stable in acidic pH or high salt conditions; in addition, they were greatly enhanced also by preheating the polymannosyl lysozyme. Thus novel surface functional properties of polymannosyl lysozyme in addition to heat stability suggest the direction of the design of new functional proteins by genetic modification. PMID- 8348975 TI - A left-handed crossover involved in amidohydrolase catalysis. Crystal structure of Erwinia chrysanthemi L-asparaginase with bound L-aspartate. AB - The crystal structure of L-asparaginase from Erwinia chrysanthemi in the presence and absence of L-aspartate was determined at 1.8 A resolution. Conserved residues in a left-handed crossover (a rare occurrence in protein structures) link pairs of dimers into the catalytically active tetrameric form of the enzyme. The structure of ErA containing bound aspartic acid shows that this unusual strand connectivity is an essential part of the active site architecture, responsible for releasing the product of the enzymatic hydrolysis. The orientation of the bound aspartate indicates for the first time a threonine residue as a catalytic nucleophile. PMID- 8348976 TI - Possible role of Na+ influx in phorbol ester-induced down-regulation of protein kinase C in HL60 cells. AB - Amiloride, an inhibitor of Na+/H+ exchange, inhibited down-regulation of protein kinase C in HL60 cells induced by tumor-promoting phorbol ester in dose-dependent manner judging from immunoblot analysis. This inhibition was observed with regard to type I (gamma), type II (beta), and type III (alpha) isozymes of protein kinase C. On the other hand, monensin, a Na+ ionophore, accelerated the down regulation of protein kinase C induced by phorbol ester. When we examined 22Na+ uptake by HL60 cells, the higher uptake was observed after stimulation with phorbol ester compared to the control cells and this 22Na+ uptake was strongly inhibited by the addition of amiloride. However, monensin further stimulated the 22Na+ uptake observed in phorbol ester-treated cells. These data suggest that the increase in intracellular Na+ concentration may be one of the triggers for the induction of down regulation of protein kinase C. PMID- 8348977 TI - Determination of the disulphide bridge arrangement of bovine histidine-rich glycoprotein. AB - Histidine-rich glycoprotein (HRG) was purified from bovine plasma and the disulphide bridge arrangement established. Disulphide-bridged peptides were obtained from peptic and tryptic degradation of native bovine HRG. Twelve half cystine residues were found in bovine HRG (compared to sixteen cysteines in human HRG), all involved in the formation of six disulphide bridges connecting Cys-1 to Cys-12, Cys-2 to Cys-3, Cys-4 to Cys-5, Cys-6 to Cys-11, Cys-7 to Cys-8, and Cys 9 to Cys-10. Additional sequence analysis of 14C-carboxymethylated chymotryptic and Staphylococcus aureus V8 protease generated peptides and CNBr-fragments of bovine HRG yielded a partial amino acid sequence of bovine HRG constituting 78% of the sequence when compared to the human cDNA sequence. PMID- 8348978 TI - Properties of alpha 1-antitrypsin secreted by human adenocarcinoma cell lines. AB - alpha 1-Antitrypsin; (alpha 1-AT) produced by various human carcinoma (non hepatoma) cell lines were analyzed. Five out of eight cell lines secreted detectable amounts of alpha 1-AT into the conditioned media. All were adenocarcinoma cell lines. The tumor cell-derived alpha 1-ATs had higher molecular weights (MW) than the normal plasma form. Most of this difference was an overall reflection of altered N-glycosylation. As judged by binding of lectins, the glycosylation had shifted towards higher levels of triantennary oligosaccharides and higher levels of fucosylation. The conditioned media also contained lower MW alpha 1-AT species, possibly, proteolytically cleaved forms. PMID- 8348979 TI - Strontium binding to sarcoplasmic reticulum Ca(2+)-ATPase. Spectroscopic differentiation of the substeps involved. AB - We investigated the consequences of Sr2+ binding to the transport sites of sarcoplasmic reticulum (SR) Ca(2+)-ATPase for two fluorescent conformational probes located in different regions of the ATPase. Using SR vesicles in which Lys 515 in the ATPase had been previously labeled with fluorescein 5'-isothiocyanate (FITC), we found that the Sr(2+)-induced a drop in the fluorescein fluorescence of this FITC-labeled ATPase shifted toward lower Sr2+ concentrations than the Sr(2+)-induced rise in Trp fluorescence for the same FITC-labeled ATPase. The curve describing the Sr(2+)-dependent rise in Trp fluorescence had a characteristic asymmetric shape, and the changes in Trp fluorescence occurred in parallel with the activation by Sr2+ of pNPP hydrolysis by the ATPase. Analysis of these results in terms of the simplest scheme describing the sequential binding of the two Sr2+ ions suggests that under the conditions of these experiments, i.e. at neutral pH in the presence of potassium, the Sr(2+)-induced rise in the Trp fluorescence mainly reflected the formation of ATPase with two ions bound to the transport sites, whereas the binding of a single Sr2+ ion was virtually sufficient to reduce the fluorescence of bound FITC to its minimal level. PMID- 8348981 TI - Enhancement of interleukin-2 (IL-2) production by 6 different cytokines: heterogeneity among IL-2 producing T cell clones. AB - The production of interleukin-2 (IL-2) by phytohemagglutinin (PHA)-stimulated human leukemia T cell lines was significantly increased by 6 different cytokines. The most effective cytokines were interleukin-1 alpha (IL-1 alpha) and IL-1 beta; less effective were interferon-alpha (IFN-alpha), tumor necrosis factor-alpha (TNF-alpha), IFN-beta and TNF-beta. The combinations of two cytokines had synergistic or additive effects and increased IL-2 production to a greater extent than either cytokine alone. Other cytokines tested, such as IL-3, IL-4, IL-6, IL 7, IL-8 and IFN-gamma, had no effect on IL-2 production. However, a remarkable heterogeneity in sensitivity to the enhancing effects of the active cytokines was found among the IL-2-producing T cell lines studied. While IL-2 production in the most sensitive cell line, MOLT-16, was increased by all 6 active cytokines, other cell lines responded by increasing IL-2 production to stimulation with only some of the cytokines tested. The production of IL-2 in T cell line H9 was not enhanced by any of the cytokines used. These results show that several cytokines can increase IL-2 production by having a direct effect on the activated IL-2 producing T cells, but also that the outcome of the regulatory effects of individual cytokines depends considerably upon the individual IL-2-producing T cell clone. PMID- 8348980 TI - Effects of anions on the Ca2+, H+ and electrical gradients formed by the sarcoplasmic reticulum ATPase in reconstituted proteoliposomes. AB - The chaotropic character of several ions determines their partition on membrane interfaces with aqueous media as predicted by the Hofmeister series. However, specific characteristics of each individual ion determine its ability to cross the membrane and to influence Ca2+, H+ and electrical gradients produced by the sarcoplasmic reticulum (SR) Ca2+ pump in reconstituted proteoliposomal vesicles. Specific effects of this kind may be relevant to a variety of biological systems, including the excitation-contraction coupling of muscle fibers in which SR plays a prominent role. PMID- 8348982 TI - Artificial mineralization in vitro--a model of tissue mineralization. AB - Calcium chloride and sodium hydrogen phosphate form precipitation zones in gelatin gel, gel supplemented with cartilaginous extract, articular cartilage slices, and in demineralized bone. The cartilaginous extract exerts a marked inhibitory effect on the crystal quantity and clustering. The pretreatment of cartilage slices with hyaluronidase increases the crystal frequency. The morphology of crystals formed in gelatin and in cartilage was similar but quite different from the precipitation pattern found in demineralized bone. PMID- 8348983 TI - Inhibition of growth of the lymphocyte lines by deferoxamine under various iron supply conditions. AB - Inhibition of growth of the lymphocyte lines by iron-binding agent deferoxamine under various iron-supply conditions was studied. Three different defined culture media, representing three different iron-supply conditions, were used: (1) ferric citrate (500 microM) medium, (2) transferrin (5 micrograms/ml) medium, and (3) low-iron medium (this medium without any iron compound added contains 0.6 microM contaminative non-transferrin iron). Mouse B cell line PLV-01, human T cell line Jurkat, and human B cell lines Raji and HSCE- were employed. Raji and HSCE- cells are able to grow in low-iron medium but PLV-01 and Jurkat cells do not grow in the medium. For all cell lines tested in ferric citrate medium, a 50% growth inhibition was achieved with 440-500 microM deferoxamine. In transferrin medium, deferoxamine concentrations of 4.4-5.5 microM were required for a 50% inhibition of PLV-01, Jurkat and HSCE- cells. For the same degree of inhibition of Raji cells, 39 microM deferoxamine was required. In the case of low-iron medium, a 50% inhibition of Raji and HSCE- cells was achieved with about 1.4-2.1 microM deferoxamine. The data demonstrate that the sensitivity of the lymphocyte lines to deferoxamine depends on iron-supply conditions. Under the same iron-supply conditions, individual cell lines can exhibit different sensitivity. However, the sensitivity does not correlate with the ability of the cell lines to grow in low iron medium. PMID- 8348984 TI - Activity of PDGF (A) gene in the human cell line derived from a renal carcinoma metastasis. AB - PDGF-like activity was investigated in conditioned media of cell cultures derived from 4 human renal carcinomas. Transient production of PDGF-like factor was found only in the cell line derived from a subcutaneously growing metastasis. Further analysis of this cell line showed an increase of PDGF (A) gene activity in one cellular clone. PMID- 8348985 TI - Changes in vascular pattern of chicken chorioallantois after cartilaginous extract, chondroitin sulfate and dextran sulfate treatment. AB - Cartilaginous extract, chondroitin sulfate C as well as dextran sulfate in gelatin pellets have an inhibitory effect on the development of fine capillaries, in contrast to pure gelatin pellets or pellets with sucrose. These results suggest an unspecific inhibitory effect of anionic saccharidic polymers on the development of chorioallantoic membrane vessels, because the chemical structure of dextran sulfate is (except anionic groups) different from chondroitin sulfate in the pure form or in the form of proteoglycans (in cartilaginous extract). PMID- 8348986 TI - Disassembly of microtubules due to low intensity ultrasound. AB - HeLa and MCF cell monolayers growing on glass cover-slips were sonicated using continuous wave ultrasound at low intensity levels approaching diagnostic conditions. The disassembly of cytoplasmic microtubules immediately after sonication was demonstrated using indirect immunofluorescence. The recovery from exposure to ultrasound, i.e. the reassembly of microtubules, was observed in the cultured cells 2 h after the sonication was discontinued. PMID- 8348987 TI - Enrichment of estradiol receptor from calf uterus. AB - A three-step procedure to enrich estradiol receptor protein from calf uterus nearly 30,000-fold has been described. Over-all yield is 12%. Control of the single steps has been performed by sodium dodecyl sulfate-electrophoresis, sucrose density gradient centrifugation, gel filtration and determination of receptor quantity. Immunological properties of the preparation obtained have not been controlled. PMID- 8348988 TI - Maintaining infection control during restorative procedures. AB - This report has listed criteria, example products, and pertinent information to aid clinicians in performing infection control procedures using products and techniques with verified efficacy. The goal is to provide optimal protection of clinicians and patients from cross-contamination in the dental environment. Subjects reviewed were face masks, eye protection, gloves, hand antiseptics, uniforms, vaccines, instrument cleaning, sterilization, environmental surface management, and contaminated waste management. The criteria proposed and the products listed were not intended to be all-inclusive or absolute. The omission of a product from this article or from the examples of products that did meet the criteria listed is not intended to disparage the product. No endorsement or approval of any product is made or intended by the author, editors, or publisher. The intent is to provide some direction at this time. Many new products and concepts now in development will bring changes in the future. The products referenced have been evaluated by independent researchers and clinicians in laboratory and clinical-use tests, and data are available upon request to support all recommendations. PMID- 8348989 TI - Adhesion and its application with restorative materials. AB - Significant progress has been made in the area of adhesion and esthetic restorative materials. Each generation of product development aims to address many of the previous inadequacies. Current resin-based dentin bonding agents are miles ahead of agents introduced only 10 years ago. The glass ionomer cement has undergone considerable evolution and barely resembles the original formulation. Whether these modified cement-resins will become established in the restorative practice remains to be seen. Or possibly, the glass ionomer cement will evolve itself out of existence into a new "class" of restorative. Numerous questions still remain unanswered in the area of adhesive materials. In particular, the confirmation of preliminary laboratory results with controlled clinical research often never surfaces, or is delayed beyond the commercial life of proprietary adhesive systems. Without such data, little confidence in adhesive behavior can be gained. More importantly, without a thorough understanding of the performance of adhesives in vivo, knowledge will never be gained relative to adhesive mechanisms that are necessary to further technology in this area. PMID- 8348990 TI - The significance of occlusion in restorative dentistry. AB - All occlusal therapy relates ultimately to the hinge position of the mandible. By consensus, the optimum hinge position is centric relation, the most anterosuperior position of the condyles in the glenoid fossae, articulating against the eminences, with the disks properly interposed. Also by consensus, the optimum occlusal scheme is mutual protection, in which the posterior teeth contact simultaneously and equally in centric occlusion, the canines disclude the posterior teeth in lateral excursions, and the anterior teeth disclude the posterior teeth in protrusion. Whenever CR cannot be used as the starting point of occlusal treatment, or when sufficient canine support is lacking, the clinician may have to prescribe a treatment condylar position other than CR or modify the occlusal scheme. Mutual protection occlusion is the simplest to develop and CR is the simplest starting point. Departures from these ideals create added complexities for the dentist. The greater the number of excursive contacts in the occlusal scheme, the more involved the equilibration of those contacts. A treatment condylar position other than CR may not be repeatable when needed, and two studies suggest that it may change over time. Without a stable, repeatable foundation supporting it, the occlusion may be in jeopardy. The removal of occlusal interferences, although not warranted as a routine prophylactic measure, is indicated under certain conditions. When beginning a significant amount of occlusal treatment, the clinicians may remove closing interference to achieve CR at the desired vertical dimension. They may remove excursive interferences that they do not want to perpetuate in the new scheme. Selective removal may alleviate the signs of trauma from occlusion. There may be periodontal justification for axializing and equilibrating occlusal forces. Nonaxial forces on teeth with cervical erosion should be reduced as a means of limiting further erosion and protecting cervical restorations. When occlusal disharmony has been shown to reactivate a TMD, an equilibration or a more extensive rehabilitation may be necessary in the second phase of TMD treatment. In the symptomatic phase of a TMD, however, only reversible measures are appropriate. In this time of fast-moving change in restorative techniques and products, all operative dentists should raise their consciousness of occlusal principles. Occlusal forces set limits on the selection of materials and often prescribe the design features needed for a successful outcome. With structurally or periodontally compromised teeth, the occlusal planning to minimize nonaxial forces lies at the heart of the restoration. Virtually all restorative dentistry is affected by the occlusal forces of the teeth in function.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8348991 TI - Trouble shooting everyday restorative emergencies. AB - Restorative emergencies present themselves nearly every day in a general practice. Both patients and staff appreciate a designed triage protocol that is followed to route patients for treatment. Although most restorative emergencies do not require immediate attention, to patients, the problem is unsettling and they would want it evaluated as soon as possible. When the necessity for the immediate treatment of an emergency is confirmed, the office schedule is least disrupted when the practitioner and staff follow restorative treatment techniques that manage the dilemma. This article has attempted to provide the dentist with some methods of triage and treatment of restorative emergencies. There are other methods for treating patients with similar emergency needs. The manner that is chosen has to be the one that works at a clinically predictable level. PMID- 8348992 TI - Pins, dowels, and other retentive devices in posterior teeth. AB - Devices used to increase retention of restorations to severely damaged posterior teeth are described, with an emphasis on pins and dowels. Advantages and disadvantages of different techniques and measures to help prevent and correct problems are presented. PMID- 8348993 TI - Esthetic applications of restorative materials and techniques in the anterior dentition. AB - The esthetic expectations of our patients can be met by doing a thorough initial examination with emphasis on periodontal health, caries incidence, occlusion, possible orthodontic corrections, esthetic needs, and economic concerns. Through proper communication with the patient, a written treatment plan can be developed that uses the various techniques of bleaching, cosmetic recontouring, direct resin bonding, porcelain veneering, or crowning to meet the patient's restorative needs. The most conservative noninvasive techniques should be evaluated first. Often, bleaching and partial direct bonding are all that is needed. If the dentition is badly worn or discolored, then more extensive treatment is indicated. Patients frequently have concerns about longevity of restorations or require very high levels of esthetic correction, which can only be accomplished with more invasive techniques. When patients understand what can be accomplished and are involved in the treatment decision, then successful results are assured. Esthetic restorative dentistry is probably the most rewarding aspect of practice today, but it is also the most challenging. New materials appear and techniques change so rapidly that it is sometimes difficult to keep up. Practitioners should acquire a thorough knowledge of available methods and materials, learn the limitations of these materials and techniques, and master skills through continuing education (courses, journals, and newsletters) as well as chairside repetition as new procedures become available. PMID- 8348994 TI - Posterior composites. State-of-the-art clinical applications. AB - Composite resins have undergone a continuous evolution since the first patent developed by Bowen in the middle 1960s. Some current formulations are an order of magnitude more wear resistant than those first used in posterior teeth. In fact, some of them are nearly as wear resistant as amalgam with respect to generalized wear. Unfortunately, however, disproportionally little effort has been expended in improving the resins' manipulative characteristics. Consequently, posterior composite resins presently fall short as an overall substitute for amalgam as a restoration material. PMID- 8348995 TI - Dental amalgam. The state of the art and science. AB - When you balance the benefits and liabilities of a modern dental amalgam, it is one of the materials that comes closet to being an ideal restorative. Its numerous clinical advantages have, in the past, made it a standard in dental care. The profession's and public's awareness of the issues surrounding the mercury content, coupled with the biased reporting of the controversy by less than responsible journalists, have served to impung the material. The dental profession has used the material successfully in its present form for almost 100 years. There are still valid questions about the material that require further scientific investigation. Investigators continue to make improvements in the alloy's strength and handling properties while limiting the mercury-release potential of the material. As we move into the twenty-first century, we are again told we will soon have a suitable replacement for dental amalgam. That is an often repeated promise for this multifunctional product. Time and sound research into the longevity and liabilities of all restorative materials as applied in the office of the general practitioner will tell us if amalgam is or is not going to disappear from the dental armamentarium in the near future. PMID- 8348996 TI - Conservative indirect restorations for posterior teeth. Cast versus bonded ceramic. AB - The practitioner today has a number of alternative restorative modalities from which to chose when faced with the necessity of restoring posterior teeth. The primary options with extensively broken down posterior teeth are cast gold and bonded ceramic inlays, onlays, and partial veneer restorations. The dentist and informed patient should make the choice of which modality is appropriate based on a number of criteria. Certainly, based on the criteria of basic physical properties, potential for marginal integrity and stability of that integrity, cast gold is the material of choice. In terms of conservation of tooth structure and systemic biocompatibility, both restoration types are excellent. With regard to effects on long-term pulpal health, much remains unknown with many of the materials used with bonded restorations at the present time. Conservative cast gold restorations have proved to be very successful in this regard over the long term. The potential for tooth strengthening with bonded restorations is certainly an exciting, but as yet, unproven, clinical reality. Thus, until those clinical data are available, the most predictable means of restoration of extensively broken down posterior teeth is with partial-coverage cast gold, protecting cusps at risk as required (Fig. 9). As mentioned previously, cast gold inlays are also a very conservative and predictable restoration (Fig. 10). Both cast gold and bonded ceramic restorations are technically demanding, but the details required to produce excellent gold castings are well defined, and can be learned readily. Much remains to be learned regarding the materials and the techniques used to fabricate bonded ceramic restorations. Priority issues would seem to be reaching a consensus regarding the details of tooth preparation and the development of improved luting resins with improved wear resistance. Simplified techniques to improve the quality of the fit of these types of restoration also are of paramount importance. The requirement for an esthetic, or, more properly, use of a tooth-colored restoration in a posterior tooth, should be evaluated carefully for each individual restoration. Often it is possible to restore a tooth with cast gold with minimal or no display of metal. The patient will then receive the long-term benefit of cast gold and not compromise on esthetics. It is our obligation as diagnosticians to educate our patients so that they are in a position to choose, when indicated, this most cost effective of restorative options. PMID- 8348997 TI - Resin-bonded prosthodontics. An update. AB - First-generation designs that covered a large area of enamel but had minimal retentive features still provided sufficient longevity to be classified as "permanent" type restorations. The goal of long-term service can be realized more consistently by incorporating second-generation designs with the ease of adhesive bonding. PMID- 8348998 TI - Restorative dentistry. Interactions with periodontics. AB - The integration of periodontal considerations with restorative planning is now the standard of care. Instilling motivation toward prevention continues to be one of our most challenging goals. A stable healthy periodontium and minimum restorative needs are the resulting rewards. With the use of available knowledge and microbial testing for both periodontitis and caries susceptibility, we now can offer our patients a higher likelihood of success in retaining natural teeth and implants. PMID- 8348999 TI - Adjunctive orthodontic therapy in restorative dentistry. AB - This article focuses on the interaction between the orthodontist and other dental specialists to facilitate combined treatment of permanent dentition and mutilated dentition. The importance of careful and precise treatment planning of such malocclusions, including a thorough restorative and periodontal treatment plan, is emphasized. Clinical examples that range from adjunctive minor orthodontic therapy to combined orthognathic surgery treatment are presented. PMID- 8349000 TI - Restorative considerations for special needs patients. AB - Individuals are living longer with more chronic and disabling conditions than previous generations of adults. In addition, they are retaining more of their natural dentition than ever before. As a result, it will be common for a dentist in practice in the next 20 to 30 years to care for many patients with special needs. These individuals offer unique challenges to the dental practitioner. Dentists must be knowledgeable in the oral aspects of various medical conditions and the systemic manifestation of oral diseases. In addition to the oral medicine aspects of practice, dentists must be skilled clinically to care for the unique restorative needs with which these patients present. As individuals age or become chronically ill, people deserve the opportunity to select from all that modern dentistry has to offer. Patients must be involved intimately in the decision making process. No dental professional should assume because a patient is old or chronically ill that he or she lacks the financial resources or the desire to maintain his or her oral health. PMID- 8349001 TI - The implant-supported single-tooth restoration. Preoperative evaluation and clinical procedure. AB - The implant-supported restoration is a relatively new and promising treatment modality. The CeraOne system offers a complete set of easy-to-use prosthetic components plus the all-ceramic and ceramometal restorative alternatives. No clinical signs of loosening have been reported since the adjunct of a torque controller that provides a tightening force of 32 Ncm to the abutment gold fixation screw. Even with these developments, however, a meticulous presurgical evaluation of the periodontium and careful fixture placement are still imperative for a successful esthetic and functional result. PMID- 8349002 TI - High-technology innovations--and limitations--for restorative dentistry. AB - Technology has brought some exciting advances to dentistry--restorations that can be produced in one appointment and fit as well as cast restorations; laser procedures that arrest early caries, etch enamel, and that the patient finds more comfortable; and improved diagnostic capabilities through computer-enhanced images. Dental applications of these technologies are in their infancy and most of the limitations discussed in this article will be eliminated in the near future. More and more applications and possibilities are continually evolving. Technology promises to enhance dentistry for the clinician and patient alike. PMID- 8349003 TI - c-Fos and related immediate early gene products as markers of activity in neuroendocrine systems. AB - Expression of c-Fos, or other immediate early gene products, by individual neurons can be used as a marker of cell activation, making staining of these proteins an extremely useful technique for functional anatomical mapping of neuroendocrine systems. Because these proteins are located in the nucleus, identification of the phenotype of the activated neuron using substances located within the cytoplasm can be accomplished with standard double-labeling immunocytochemical techniques. Although it is clear that neurons have the capacity to express a number of immediate early gene products, what remains to be established is whether there is a different pattern of expression following various stimuli. In our studies, we focus primarily on expression of one immediate early gene product, the c-Fos protein. We also include some experiments using expression of other members of the Fos family and Jun proteins as markers for neuronal activation. Our studies describe uses of c-Fos expression in both parvocellular and magnocellular hypothalamic systems to address the following issues: (a) identification of neuroendocrine cells activated by specific treatments and conditions, (b) ascertainment of functional differences in subpopulations activated by specific stimuli, (c) evaluation of neuronal activity in complex areas containing multiple neuroendocrine systems, (d) identification of other brain areas activated in conjunction with neuroendocrine systems following specific stimuli, (e) analysis of connectivity of activated neuroendocrine systems with other parts of the brain, and (f) identification of stimuli that decrease neuronal activity. The neuroendocrine systems studied include those that secrete arginine vasopressin (AVP), oxytocin (OT), corticotropin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LHRH), and dopamine (DA). The use of c-Fos expression has permitted functional neuroanatomical mapping of these systems in response to specific stimuli such as cholecystokinin (CCK), hyperosmolality, and volume depletion, or during various physiological states such as the proestrous ovulatory luteinizing hormone (LH) surge and lactation. Although the use of c-Fos as a marker of neuronal activation will continue to be an extremely powerful technique, future studies will also be directed at relating immediate early gene expression to changes in neuroendocrine gene expression. To this end, we have shown that both c-Fos and c-Jun are expressed in neuroendocrine neurons in response to a number of stimuli, setting the stage for potential regulatory drive to genes containing AP-1 binding sites. PMID- 8349004 TI - Blood, pituitary, and brain renin-angiotensin systems and regulation of secretion of anterior pituitary gland. AB - In addition to increasing blood pressure, stimulating aldosterone and vasopressin secretion, and increasing water intake, angiotensin II affects the secretion of anterior pituitary hormones. Some of these effects are direct. There are angiotensin II receptors on lactotropes and corticotropes in rats, and there may be receptors on thyrotropes and other secretory cells. Circulating angiotensin II reaches these receptors, but angiotensin II is almost certainly generated locally by the pituitary renin-angiotensin system as well. There are also indirect effects produced by the effects of brain angiotensin II on the secretion of hypophyseotropic hormones. In the anterior pituitary of the rat, the gonadotropes contain renin, angiotensin II, and some angiotensin-converting enzyme. There is debate about whether these cells also contain small amounts of angiotensinogen, but most of the angiotensinogen is produced by a separate population of cells and appears to pass in a paracrine fashion to the gonadotropes. An analogous situation exists in the brain. Neurons contain angiotensin II and probably renin, but most angiotensin-converting enzyme is located elsewhere and angiotensinogen is primarily if not solely produced by astrocytes. Angiotensin II causes secretion of prolactin and adrenocorticotropic hormone (ACTH) when added to pituitary cells in vitro. Paracrine regulation of prolactin secretion by angiotensin II from the gonadotropes may occur in vitro under certain circumstances, but the effects of peripheral angiotensin II on ACTH secretion appear to be mediated via the brain and corticotropin-releasing hormone (CRH). In the brain, there is good evidence that locally generated angiotensin II causes release of norepinephrine that in turn stimulates gonadotropin-releasing hormone secreting neurons, increasing circulating luteinizing hormone. In addition, there is evidence that angiotensin II acts in the arcuate nuclei to increase the secretion of dopamine into the portal-hypophyseal vessels, inhibiting prolactin secretion. Central as well as peripheral angiotensin II increases CRH secretion, but there is little if any evidence that angiotensin II mediates the ACTH responses to other stressful stimuli. PMID- 8349005 TI - Activation of neutrophils NADPH oxidase by PMA: cytosol activity is translocated in phorbol-primed neutrophils. AB - 1. Translocation of cytosol activity in phorbol-primed neutrophils was studied. 2. Prior exposure of PMA or FMLP could potentiate the oxidative response by subsequent heterogeneous stimulus, FMLP or PMA. 3. In FMLP-primed neutrophils, the cytosol had almost the same activity as resting one and cytosol activity was not eluted from the membrane. 4. In PMA-primed neutrophils, however, the cytosol had less activity and cytosol activity was correspondingly eluted from the membrane. 5. These observations suggested that cytosol activity was translocated in PMA-primed cells. PMID- 8349006 TI - Hormonal regulation of human apolipoprotein E gene expression in HepG2 cells. AB - 1. Hormonal regulation of apolipoprotein E (apoE) gene expression by insulin and thyroid hormone was studied in a human hepatoma cell line, HepG2. 2. Changes at the mRNA level, mRNA translation, in vivo synthesis and secretion were monitored. 3. Both insulin and triiodothyronine were found to have no significant effect on apoE mRNA levels. 4. Insulin treatment caused an inhibition of: (a) the in vitro translation of endogenous apoE mRNA in a HepG2 cell-free system (25%), and (b) the incorporation of radioactivity into newly-synthesized apoE in an in vivo pulse-chase labeling experiment (32%). 5. Interestingly, apoE secretion rate was found to be significantly reduced with insulin (84%) suggesting that a major portion of newly-synthesized apoE may be shunted into a degradative pathway. 6. Using a similar experimental approach, triiodothyronine showed no significant effect on the rate of apoE synthesis or translation (6-15% decrease), however a slight reduction (20%) in secretion rate was shown. 7. Overall, apoE gene expression does not appear to be influenced by triiodothyronine significantly but is modulated by insulin at the translational and post-translational level. PMID- 8349007 TI - Isolation of chromaffin cell thapsigargin-sensitive Ca2+ store in light microsomes from bovine adrenal medulla. AB - 1. A subcellular fractionation procedure for bovine adrenal glands was designed with the aim to study the biochemical properties of Ca2+ stores in chromaffin cells. 2. The thapsigargin-sensitive compartment of Ca2+ stores was found to be highly enriched in a light microsomal fraction (LMF) on a 15-30% linear sucrose gradient, and was found to be essentially devoid of contamination by plasma, mitochondrial or secretory granule membranes. 3. A Ca(2+)-pumping ATPase was identified in this LMF as a 97 kDa protein forming an acid-stable, Ca(2+) dependent, thapsigargin-sensitive phosphorylated intermediate upon incubation with [gamma-32P]ATP, suggesting this protein to represent a SERCA-3 isoform of Ca2+ ATPases. 4. A major 162 kDa protein, previously demonstrated in the isolated chromaffin cells, was enriched in the LMF, distributing on sucrose gradients in parallel with the thapsigargin-sensitive Ca2+ uptake. 5. LMF appears to represent a part of the thapsigargin-sensitive Ca2+ store of chromaffin cells, and should be useful for further studies of the store properties at the subcellular and molecular level. PMID- 8349008 TI - Interaction of pyridoxal phosphate with thymidylate synthase: spectral and equilibrium dialysis studies. AB - 1. Changes in the spectrum of pyridoxal phosphate (PLP) were produced by adding an equimolar amount of native thymidylate synthase, but not by adding denatured enzyme or enzyme modified by sulfhydryl-blocking reagents. 2. The dissociation constant of the thymidylate synthase-PLP complex determined by equilibrium dialysis was 9 +/- 1.6 microM, the maximum number of PLP molecules bound per molecule of native thymidylate synthase was 2.5 +/- 0.4, and the Hill coefficient was 0.97. 3. No evidence of PLP binding was found with denatured thymidylate synthase, and only slight binding was observed when enzyme SH groups were blocked or when the active site was blocked with 5-fluorodeoxyuridylate (FdUMP) and methylene tetrahydrofolate. 4. The presence of dUMP, dTMP, or FdUMP interfered with the binding of PLP to thymidylate synthase, and the presence of equimolar amounts of PLP interfered with the binding of dUMP. PMID- 8349009 TI - Control of mucin molecular forms expression by salivary protease: differences with caries. AB - 1. A protease activity capable of degradation of the high mol. wt salivary mucus glycoprotein to a low mol. wt glycoprotein form was identified in human submandibular gland secretion. 2. The protease exhibited optimum activity at pH 7.0-7.4, and gave on SDS-PAGE under reducing conditions two major protein bands of 48 and 53 kDa. The enzyme showed susceptibility to PMSF, alpha 1antitrypsin, and egg white and soybean inhibitors, a characteristic typical to serine proteases. 3. The activity of the protease towards the high mol. wt mucus glycoprotein was found to be 3.8-fold higher in submandibular gland secretion of caries-resistant individuals than that of caries-susceptible. Furthermore, the enzyme from both groups displayed greater activity against the mucus glycoprotein of caries-resistant subjects. 4. Since the low mol. wt salivary mucus glycoprotein form is more efficient in bacterial clearance than the high mol. wt mucin, the enhanced expression of this indigenous salivary protease activity towards mucin may be the determining factor in the resistance to caries. PMID- 8349010 TI - Okadaic acid inhibits insulin stimulation of both ornithine decarboxylase and spermidine transport in hepatocyte cultures. AB - 1. Okadaic acid inhibited basal ODC activity in rat hepatocytes in culture and prevented any increase in ODC activity and in the rate of spermidine uptake promoted by both insulin and hypotonicity. 2. The increase promoted by AIB was not counteracted by okadaic acid. PMID- 8349011 TI - Diffusion limited component of mitochondrial F1-ATPase. AB - 1. The possibility that the rate of ATP hydrolysis by F1-ATPase approaches the diffusion-controlled limits was investigated by measuring the values of kcat and kl (kcat/Km) as a function of increasing viscosity. 2. The values of kcat/Km decrease significantly with increasing viscosity; further such decrease was lower when Fl-ATPase hydrolyzed poor substrate such as Ca- and Mg-ITP or when the hydrolysis rates were measured at temperatures below 20 degrees C. 3. Viscosity also decreases kcat, but only at high concentrations of viscosogenic agents. 4. These results suggest that ATP hydrolysis is at least partly diffusion controlled, although a general nonspecific perturbation in the enzyme structure is also effected by viscosity. PMID- 8349012 TI - Subcellular and developmental studies of the tyrosyl protein sulfotransferase in rat brain. AB - 1. Tyrosyl protein sulfotransferase (TPS) activity in the newborn and mature rat brain was studied using the cholecystokinin derivative terbutyloxycarbonyl-Asp Tyr-Met-Gly-Trp-Met-Asp-PheNH2, BocCCK-8(ns), as the peptide substrate. 2. TPS activity was enriched 4 times in the microsomal and synaptic vesicular enriched fractions of rat cerebral cortex. 3. CCK-8 content, in the subcellular fractions and the peptide sulfation activity distribution was in accord with the hypothesis that tyrosyl protein sulfotransferase plays a key role in the maturation process of bioactive CCK. 4. TPS activity measured in membranes from newborn brain was 2.5 times higher than the activity observed in the mature brain membranes with a Vmax = 0.83 +/- 0.05 and 0.31 +/- 0.02 respectively. The apparent KM for the sulfate donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), was similar, 94 +/- 4 nM and 90 +/- 6 nM and the KM for the peptide substrate, BocCCK-8(ns), was 234 +/- 16 microM and 160 +/- 12 microM in the newborn and adult brain membranes respectively. 5. TPS activity reached normal mature values within 20 days of age. 6. These data support the idea that tyrosyl protein sulfation is an important process in the secretion mechanism and in the CCK maturation. PMID- 8349013 TI - Characterization of sheep hepatocytes in primary culture. AB - 1. Primary cultures of isolated sheep hepatocytes were used to characterize metabolic functions of liver: gluconeogenesis, ureagenesis and protein synthesis. The rates of all three metabolic activities were linear over a 20 hr culture period. 2. Hepatocytes in the presence of glucagon increased the synthesis of urea by approx 30% (P < 0.05) and increased release of glucose into the medium by 60% (P < 0.05). 3. In the absence of insulin, significantly more (35%; P < 0.05) glucose was released in the medium than in the presence of insulin. 4. Results help evaluate the primary culture of sheep hepatocytes as an appropriate experimental model to study nutritional and hormonal regulation of liver in the ruminant species. PMID- 8349014 TI - Adenosine effect on lactate and pyruvate production in the hypoxic guinea pig heart. AB - 1. It has been shown that adenosine stimulates glycolysis in some cells and this ability of adenosine was tested in the hypoxic guinea pig heart. 2. Adenosine (10 microM) activated lactate production in the isolated perfused guinea pig heart under conditions of normoxia but did not under hypoxia. 3. Despite this, the nucleoside favorably influenced the energy metabolism of the hypoxic heart as revealed by the better posthypoxic functional recovery (98%) compared to the control without adenosine (78%). 4. Our findings suggest a role for the glycolytic pathway in this effect of the nucleoside as long as other cardiac energy-yielding pathways are strictly aerobic. PMID- 8349015 TI - Role of antiproteolytic heparin-binding serum protein(s) in modulating the levels of sialyl- and galactosyltransferase activity released during the incubation of rat jejunal slices. AB - 1. Sialyltransferase released into the medium during the incubation of rat jejunal slices in serum-free buffer, was susceptible to proteolytic degradation. Heat inactivated horse serum or its antiproteolytic heparin-binding fraction was found to be necessary in determining the activity of sialyltransferase released (Nadkarni et al., 1991). 2. In the present study, we have shown that heat inactivated rat serum (HRS) or its antiproteolytic heparin-binding fraction (HBF) had a role in determining the sialyltransferase activity released during jejunal slice incubations. 3. Galactosyltransferase was also released during incubations, but was not proteolytically degraded and the presence of HRS or HBF in incubations did not alter the levels of galactosyltransferase activity released. 4. Trypsin activity in serum-free incubation medium was higher compared to medium containing HRS. 5. Addition of serum-free medium obtained from 4 hr incubations of the jejunal slices, to medium obtained from parallel incubations done in the presence of HRS, caused inhibition of sialyl- but not galactosyltransferase activity. 6. In jejunal homogenates stored at -20 degrees C, sialyltransferase activity was decreased during 0-45 days of storage, whereas galactosyltransferase activity remained fairly stable for upto 56 days. 7. Inclusion of HRS or HBF in homogenates resulted in higher sialyl- but not galactosyltransferase activity compared to serum-free homogenate samples. 8. The results suggest that HRS or its antiproteolytic heparin-binding proteins have a role in determining the sialyltransferase activity released from the jejunal slices. In contrast galactosyltransferase released was not susceptible to proteolysis, and HRS or HBF was not required to express its activity. PMID- 8349016 TI - Binding of drugs to human plasma proteins, exemplified by Sn(IV)-etiopurpurin dichloride delivered in cremophor and DMSO. AB - 1. The mode-delivery-effect upon the binding of Sn(IV)-etiopurpurin dichloride (SnET2) in human plasma has been studied by ultracentrifugation, combined with absorption and fluorescence spectroscopy. SnET2 was delivered to plasma either in Cremophore EL (CRM) or in dimethyl sulfoxide (DMSO). To facilitate interpretation, optical, conductivity and aggregation properties of SnET2 were obtained for various solutions. 2. The second order rate constant for the aggregation of SnET2 monomers seemed to be remarkably small, of the order of 10(3) M-1 min-1. 3. SnET2 was bound as monomeric entities. Such entities had environmental-sensitive fluorescent properties dependent on the type of protein or solvent (DMSO, CRM, H2O) with which they interacted. 4. SnET2 showed saturable binding with high density subfraction(s) of high density lipoproteins and with one or more high density proteins. Complete or substantial saturation was achieved at the SnET2 level of 3.5 micrograms/ml. Such binding might be mediated by apolipoprotein D and alpha 1-acid glycoprotein. 5. There was little effect of SnET2 concentrations (3.5-35 micrograms SnET2/ml) upon the plasma binding of SnET2, irrespective of the mode of delivery. 6. The percentages of SnET2 bound to low density lipoproteins (LDL), high density lipoproteins (HDL), and high density proteins (HDP) were 10, 70 and 20%, respectively, for delivery in DMSO. The value for LDL also includes binding with very low density lipoproteins (VLDL). For delivery in CRM the corresponding values were 20, 50 and 30%. Apparently, CRM interacted with HDL entities and reduced their affinity for SnET2. 7. The distribution pattern of SnET2 among lipoproteins reflects interactions with apoproteins and/or with surface phospholipids rather than with core lipid constituents of lipoproteins. 8. Conductivity measurements showed that SnET2 was partly an ionic entity in water. 9. The plasma binding of SnET2 is compared with the corresponding binding of other drugs, both tetrapyrroles and nontetrapyrroles. PMID- 8349017 TI - Isolation and characterization of procoagulant from the venom of Vipera aspis aspis. AB - 1. A procoagulant protein was isolated from Vipera aspis aspis (Aspic viper) venom by Sephadex G-75, DEAE-Sephacel, Q-Sepharose and Sephadex G-150 column chromatography. 2. The purified protein has a molecular weight of 125,000 and an isoelectric point of 4.3. 3. This procoagulant decreased the clotting time of plasma from humans, however, direct fibrongen clotting activity was not detected. 4. Diisopropyl fluorophosphate, a serine-protease inhibitor affected coagulant activity of purified protein significantly, while a factor Xa inhibitor (3-ABPE) possessed a slight inhibitory effect. 5. Bovine prothrombin incubated with isolated protein, phospholipid emulsion, bovine factor V and calcium ions drastically decreased the clotting time of fibrinogen and expressed hydrolytic activity against synthetic arginine esterase substrates. However, no hydrolytic activity these substrates was detected with the procoagulant alone indicating that this protein might participate in activation of prothrombin. PMID- 8349018 TI - Characterization of immunotrap assays for urokinase plasminogen activator and its inhibitors and measurements of these molecules in human plasma and mouse macrophage in culture. AB - 1. Immunotrap assays that can measure the activities of urokinase-type plasminogen activator (uPA) and its inhibitors (PAIs) were characterized. 2. Both human plasma and mouse macrophages in culture were found to contain much higher inhibitor activity than uPA-like activity. 3. The balance between pro- and anti fibrinolytic activities was quantitatively changed in the murine macrophages after the injection of thioglycollate. uPA-like materials were synthesized by the macrophages and secreted to the conditioned medium continuously, while PAI activity was unchanged during the same time period. PMID- 8349019 TI - Mitogenic activity and immunological properties of bolesatine, a lectin isolated from the mushroom Boletus satanas Lenz. AB - 1. A lectin has been purified from the mushroom Boletus satanas Lenz. 2. The protein, called bolesatine, is mitogenic for human T lymphocytes in a dose- and time-dependent manner. 3. Optimal mitogenic doses induce the release of interleukin-1 alpha and interleukin-2 from mononuclear cell cultures. PMID- 8349021 TI - The sheep erythropoietin gene: molecular cloning and effect of hemorrhage on plasma erythropoietin and renal/liver messenger RNA in adult sheep. AB - Erythropoietin (Epo) production was studied in adult sheep. Nine ewes, body weight (BW) 39 +/- 1.3 kg, were hemorrhaged a volume of blood equivalent to 1.6% BW, and sampled at 0, 2, 4, 6, 24 h. Oxygen content (O2 CT) decreased by 2.7 +/- 0.6 ml/dl at 2 h. Plasma immunoreactive (IR) Epo was only significantly increased at 24 h, from 18.5 +/- 3.5 to 40 +/- 10.7 mU/ml (mean +/- SEM). A further 5 ewes were bled extensively (2793 +/- 82 ml) over 54 h, and killed for Epo mRNA determination. The O2 CT decreased from 12.3 +/- 1.6 to 4.1 +/- 0.6 ml/dl, and plasma Epo increased from 15 +/- 4 to 1675 +/- 287 mU/ml. The sequence of ovine Epo cDNA was derived from the kidney RNA of a severely bled sheep using reverse transcription/polymerase chain reaction (RT/PCR), and from an ovine Epo genomic clone. The cDNA encodes a peptide of 194 amino acids, including a 27 amino acid signal peptide. The deduced amino acid sequence of sheep Epo shows 82%, 78% and 80% homology with mature Epos of human, mouse and monkey, respectively. The gene structure resembles closely those of human and mouse, with 5 exons and 4 introns. The expression of the ovine Epo gene in tissues from normal and hemorrhaged sheep was analysed by a competitive RT/PCR method. Epo mRNA was difficult to detect in liver from normal sheep, but was detectable at 0.01-0.04 amol/microgram total RNA in kidney from normal sheep. In the kidneys of severely bled sheep, the Epo mRNA levels (per micrograms total RNA) increased 400-1500-fold compared to that of normal kidneys, and were approximately 60-fold greater than those in the livers of the hemorrhaged sheep. PMID- 8349020 TI - Molecular mechanisms regulating prostaglandin action. PMID- 8349022 TI - The secretion of transforming growth factor-beta by bovine luteal cells in vitro. AB - Transforming growth factor-beta (TGF-beta), a multifunctional polypeptide growth factor, is produced by follicular cells in the ovary. However, there is little information indicating that TGF-beta is produced in the post-ovulatory follicle, i.e. the corpus luteum. In the present communication we present evidence that bovine luteal cells secrete large amounts of TGF-beta when maintained in moderate term monolayer culture. Using TGF-beta 1 and TGF-beta 2 subtype-specific antibodies to neutralize the bioactivity it was found that 80-90% TGF-beta activity in luteal cell conditioned medium (LCCM) is due to TGF-beta 1, whereas < or = 10% TGF-beta activity in LCCM is due to TGF-beta 2. TGF-beta subtype nonspecific antibodies effectively and completely neutralized all TGF-beta activity in LCCM. The ratio of TGF-beta 1:TGF-beta 2 as estimated on the basis of neutralization studies was supported by visual observation of TGF-beta 1 and TGF beta 2 protein bands on Western blotting. Using a modified and rapid mink lung epithelial cell bioassay and authentic TGF-beta to generate standard curves, the amount of TGF-beta secreted by luteal cells in vitro was quantitated. The concentration of luteal cell secreted proteins in the medium increased with time during 7 days of culture. Likewise, the TGF-beta concentration in LCCM increased during 7 days. To study the effect of duration of culture on the rate of TGF-beta secretion by luteal cells, conditioned medium was collected at 24 h intervals and replaced with fresh nutrient medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349023 TI - Biphasic effect of exogenous testosterone on follicle-stimulating hormone gene expression and synthesis in the male rat. AB - Effects of 2-week treatments with increasing doses of testosterone (T) on gonadotropin gene expression and secretion were studied in intact and acutely castrated male rats. T was administered in silastic capsules with lengths of 2, 4, 8 or 16 cm, and control animals received empty capsules (eight per treatment). The treatments increased serum T up to 3-fold of control levels. In intact animals, the 2-8 cm capsules suppressed pituitary follicle-stimulating hormone beta (FSH beta) mRNA contents by 40-50% (p < 0.01), but 16 cm of T returned the levels back to control range. Castration alone increased the FSH beta mRNA level 2.3-fold (p < 0.01) and, after T treatment, the FSH beta message returned to control levels indistinguishable from intact controls but higher than in intact animals receiving the same T dose. Pituitary luteinizing hormone-beta (LH beta) mRNA displayed a dose-dependent suppression in response to T, to 32-35% of controls (p < 0.01) with the 8 and 16 cm capsules. Castration increased this message 10-fold, and additional T treatment suppressed the levels to the range of T-treated intact animals. Pituitary common-alpha mRNA decreased to 30-31% of controls by 2, 4 and 8 cm of T (p < 0.01), but the highest dose of T increased the common-alpha contents, in comparison to the other doses, to 54% of controls (p < 0.01). Castration alone increased the common-alpha contents 4.4-fold, and there was a dose-dependent suppression of this parameter by T down to the range of T-treated intact rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349024 TI - Calcitriol attenuates the thyrotropin-releasing hormone-stimulated inositol phosphate production in clonal rat pituitary (GH4C1) cells. AB - Three days pretreatment of the prolactin (PRL) secreting GH4C1 cells with 10 nM calcitriol attenuated both the basal and thyrotropin-releasing hormone (TRH) stimulated (1 microM, 5 s) inositol trisphosphate (IP3) production by 30 and 26%, respectively. The effect was detectable at 10 nM (basal) and 1 pM (TRH stimulated), and maximal at 1 microM (basal) and 10 nM (TRH), respectively. Calcitriol was at least 100 times more potent than calcidiol and 24 hydroxycalcidiol, and the effect was reversible upon cessation of pretreatment. Calcitriol pretreatment (1 microM, 5 days) also decreased the levels of phosphatidyl-inositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate by 23, 55 and 32%, respectively. GTP gamma S-stimulated (100 microM, 30 s) IP3 production was decreased by 45% after calcitriol pretreatment (10 nM, 5 days). Pertussis toxin (1 nM, 4 h) attenuated both the basal and TRH stimulated IP3 production, but this effect was omitted by calcitriol pretreatment. Thus, calcitriol specifically attenuates both the basal and TRH stimulated inositol phosphate production in GH4C1 cells. The mechanism, at least partly, involves decreased availability of phosphoinositides for phospholipase C. Calcitriol regulation of a pertussis toxin-sensitive G-protein might also play some role. PMID- 8349025 TI - Characterization of the ovine LH beta-subunit gene: the promoter directs gonadotrope-specific expression in transgenic mice. AB - The alpha- and beta-subunits of the gonadotropin hormones are expressed in the gonadotrope cells of the anterior pituitary. There are no adequate in vitro systems for the analysis of beta-subunit gene expression. In this study, therefore, transgenic mice have been used to investigate the regulation of expression of the ovine luteinizing hormone beta-gene (oLH beta) in vivo. oLH beta was isolated, characterized, and 1.9 kb of the promoter fused to the bacterial reporter chloramphenicol acetyl-transferase (CAT). Three lines of transgenic mice were generated. CAT enzyme was detected in the pituitary of two lines, whereas the third line did not express. Measurement of endogenous luteinizing hormone and follicle stimulating hormone levels in both expressing lines revealed small differences when compared to controls, but these did not affect the fertility of the animals. Immunostaining of the anterior pituitary revealed that the oLH beta CAT transgene was expressed specifically in gonadotrope cells. PMID- 8349026 TI - Gender-associated differences in the development of 5-aminolevulinate synthase gene expression in the harderian gland of Syrian hamsters. AB - The mRNA levels for aminolevulinate synthase (ALV-S), the rate-limiting enzyme in porphyrin synthesis, were studied in male and female Syrian hamsters during postnatal development. Sex-associated differences in the expression of ALV-S gene were evident at the end of the third week of postnatal development. Serum levels of luteinizing hormone (LH), testosterone, cortisol, thyroid hormones and insulin like growth factor were also studied in order to correlate their concentrations with the mRNA levels for ALV-S. Among these hormones, serum LH levels showed a positive correlation with the ALV-S mRNA levels. However, the expected negative correlation with testosterone levels was not clearly observed. Thus, in order to test the effects of testosterone on ALV-S gene expression, 11-day-old male and female Syrian hamsters and adult female hamsters were injected with 50 micrograms of testosterone for 4 days. Testosterone administration decreased the levels of ALV-S mRNA in the adult females but did not influence those of young females. The possible explanation for the insensitivity to testosterone during these postnatal stages might involve the maturational state of androgen receptors in the Harderian glands. PMID- 8349027 TI - The gill calcium transport cycle in rainbow trout is correlated with plasma levels of bioactive, not immunoreactive, stanniocalcin. AB - Stanniocalcin (STC) is an inhibitor of gill Ca2+ transport that is produced by the corpuscles of Stannius, endocrine glands in bony fish. In young rainbow trout (Oncorhynchus mykiss), there are cyclical changes in the rate of gill Ca2+ transport, with alternating phases of accelerated and reduced uptake every 14 days. Previous studies by our laboratory have established that the responsiveness of young trout to the inhibitory effects of exogenous STC is dependent on this cycle. Trout are highly responsive to STC at peaks of Ca2+ uptake and unresponsive at nadirs, which has led us to suggest that the gill Ca2+ transport cycle may be regulated by a reciprocal cycle in the levels of plasma STC. In this report, we have further characterized the gill Ca2+ transport cycle in salmonids and investigated the role of STC in its regulation. Our results showed that the cycle is synchronous and is likely a characteristic feature in all salmonids but that it varies in amplitude between species. Surprisingly, we observed no correlation between circulating levels of radioimmunoassayable STC and the rate of gill Ca2+ transport in trout. To address this apparent contradiction, trout fry were passively immunized with STC antiserum to determine if there were variable amounts of bioactive STC in the circulation, at times when trout were either more or less sensitive to exogenous STC. We observed that during the times when trout were responsive to STC treatment (i.e., cycle peaks), passive immunization had no effect on the rate of gill Ca2+ transport in fish from the same population, indicating that there were low levels of bioactive STC in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349028 TI - Pituitary and hypothalamic insulin-like growth factor-I (IGF-I) and IGF-I receptor expression in food-deprived rats. AB - The present study was designed to evaluate a possible role for the insulin-like growth factor-I (IGF-I) system in mediating the suppression of growth hormone (GH) secretion observed in food-deprived rats by measuring IGF-I mRNA, receptor concentration and receptor mRNA in neuroendocrine tissues (hypothalamus and pituitary). Rats were deprived of food (food-deprived) for 72 h or had free access to food (fed). Tissues were processed for measurement of steady-state levels of: (a) IGF-I and IGF-I receptor mRNA (by solution hybridization/RNase protection assay); (b) IGF-I in serum and tissue extracts (by RIA) and (c) IGF-I displaceable [125I]IGF-I binding to plasma membrane preparations. Food deprivation resulted in decreased serum and liver levels of IGF-I. Kidney IGF-I mRNA levels were reduced 80% in food-deprived rats with a concomitant increase in IGF-I receptor concentration and mRNA levels. Refeeding of food-deprived rats fully normalized these perturbations. Pituitary IGF-I content was reduced 50% in food-deprived rats while IGF-I mRNA levels were unaffected. A modest increase was seen in pituitary IGF-I receptor concentration; however, IGF-I receptor mRNA levels were not changed. Hypothalamic IGF-I mRNA content was reduced in 72 h food deprived rats while IGF-I receptor binding capacity and mRNA were unaffected. In conclusion, IGF-I mRNA levels are decreased in liver, kidney and hypothalamus together with a reduction in plasma IGF-I in food-deprived rats but is unaffected in anterior pituitary. IGF-I receptor gene expression and binding capacity are coordinately regulated in kidney and hypothalamus, but not in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349029 TI - Expression of human thyroid peroxidase in insect cells using recombinant baculovirus. AB - The baculovirus expression system was used to overexpress recombinant human thyroid peroxidase. Sf-9 cells infected with the recombinant virus AcMNPV-hTPO synthesized hTPO protein (hTPO-bac) immunogenic on Western blots when probed with either rabbit anti-TPO peptide sera or pooled human anti-TPO sera (MS12/89). hTPO bac was a major constituent of the membrane fraction from the infected cells, constituting 14.9% and 10.1% of the 1% deoxycholate-soluble and insoluble fractions, respectively, as judged by densitometry. Recombinant hTPO-bac was extracted from cellular membranes with 1% deoxycholate and partially purified by Sepharose 6B column chromatography. Specific immunoreactivity of MS12/89 to hTPO bac on microtiter plates was seen using ELISA. Detergent extract from wild-type virus-infected Sf-9 cells was used as background control antigen; no specific reactivity to either hTPO-bac or control antigen was seen with control sera. To determine antigenic potency, MS12/89 was incubated with increasing concentrations of various preparations of hTPO antigen and with ovalbumin as control. The capacity of the partially purified hTPO-bac to immunoneutralize human anti-hTPO standard at 50% inhibition of binding was 0.01 U/microgram hTPO-bac (NIBSC Units), compared with 0.5 U/microgram and 0.06 U/microgram for natural hTPO and CHO-hTPO, respectively. When ELISA was performed using clinical samples of human sera to detect hTPO autoantibodies, results using hTPO-bac correlated well with those using hTPO from Graves' thyroid tissue (r = 0.85, p = 0.02) and those using recombinant hTPO from Chinese hamster ovary cells (hTPO-CHO) (r = 0.85, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349030 TI - Thyrotropin regulates thyroglobulin mRNA splicing and differential processing. AB - Rat thyroid tissue and cultured rat thyrocyte lines contain two thyroglobulin (Tg) mRNAs: a 9 kb rTg-1 mRNA encoding the 330, kDa Tg monomer and a recently described 0.95 kb rTg-2 mRNA. These transcripts have identical 5' coding sequences (641 nucleotides); however, the 3' end of rTg-2 is comprised of coding and non-coding sequences not present in rTg-1. To determine if a single Tg gene encoded both mRNA species, a genomic clone was isolated which spanned the full length rTg-2 cDNA sequence. The promoter sequence and restriction map were the same as for the previously characterized rTg-1 gene, indicating that rTg-1 and rTg-2 mRNAs are splicing variants derived from the same Tg gene. The unique 3' end of rTg-2 mRNA comprised a single exon which was intronic with respect to rTg 1 mRNA formation. The level of rTg-2 in cultured rat thyrocytes was more sensitive to thyrotropin (TSH) regulation than was rTg-1. rTg-2 mRNA was rapidly (and reversibly) depleted to nearly undetectable levels after TSH removal, unlike rTg-1. Conversely, TSH rapidly restored control levels of rTg-2 mRNA in such depleted cells. The data thus support a model of TSH-induced splicing and regulation of the two Tg mRNAs in the rat. PMID- 8349031 TI - Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM. AB - Potentiation of glucose-induced insulin secretion by intestinal factors has been described for many years. Today, two major peptides with potent insulinotropic action have been recognized: gastric inhibitory peptide and truncated forms of glucagon-like peptide I, GLP-I(7-37) or the related GLP-I(7-36)amide. These hormones have specific beta-cell receptors that are coupled to production of cAMP and activation of cAMP-dependent protein kinase. Elevation in intracellular cAMP levels is required to mediate the glucoincretin effect of these hormones: the potentiation of insulin secretion in the presence of stimulatory concentrations of glucose. In addition, circulating glucoincretins maintain basal levels of cAMP, which are necessary to keep beta-cells in a glucose-competent state. Interactions between glucoincretin signaling and glucose-induced insulin secretion may result from the phosphorylation of key elements of the glucose signaling pathway by cAMP-dependent protein kinase. These include the ATP dependent K+ channel, the Ca++ channel, or elements of the secretory machinery itself. In NIDDM, the glucoincretin effect is reduced. However, basal or stimulated gastric inhibitory peptide and glucagon-like peptide I levels are normal or even elevated, suggesting that signals induced by these hormones on the beta-cells are probably altered. At pharmacological doses, infusion of glucagon like peptide I but not gastric inhibitory peptide, can ameliorate postprandial insulin secretory response in NIDDM patients. Agonists of the glucagon-like peptide I receptor have been proposed as new therapeutic agents in NIDDM. PMID- 8349032 TI - Impaired arteriolar myogenic reactivity in early experimental diabetes. AB - Hyperperfusion and an increase in capillary pressure has been implicated in the pathogenesis of diabetic microangiopathy. The existence of such alterations suggests that the myogenic response to increased intravascular pressure may be altered in diabetes. To examine this, in vivo studies were performed on the rat cremaster muscle microcirculation of age-matched control and STZ-induced (65 mg/kg) diabetic rats (3-4 wk of diabetes). Anesthetized rats were enclosed in an airtight Plexiglas box with the cremaster muscle exteriorized into an organ bath containing Krebs' solution. To study myogenic responsiveness, box pressure was increased in steps of 10 mmHg from 0 to 30 mmHg for 2 min. Third-order arterioles of the control animals (lumen diameter 18 +/- 2 microns) responded to increased pressure with a rapid onset vasoconstriction. In contrast, the rate of development of the constriction was markedly attenuated in similar vessels (15 +/ 1 micron) of the diabetic animals, despite their ability to exhibit a similar maximal arteriolar constriction to that of the control animals. When 20 mmHg pressure steps were applied for only 10 s, arterioles of the diabetic animals constricted minimally, whereas those of the control animals constricted to 75% of the maximal response expected for that pressure increase (P < 0.01). Second-order arterioles of both groups of animals responded with a primarily passive distension to increased intravascular pressure suggesting that the impaired responsiveness of the third-order arterioles is not compensated for by an increase in the myogenic responsiveness of upstream vessels. Basal intravascular pressures, measured in first-, second-, and third-order arterioles, were similar in control and diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349033 TI - Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia. AB - Hypoglycemia has been incriminated as a possible factor responsible for development of the hypoglycemia unawareness phenomenon in patients with type I diabetes. Many patients with this condition, however, do not have a history of recent hypoglycemia. Because asymptomatic nocturnal hypoglycemia commonly occurs in type I diabetes, we tested the hypothesis that such episodes might be capable of inducing this phenomenon. Accordingly, autonomic and neuroglycopenic symptoms, counterregulatory hormone responses, and cognitive function were assessed during standardized insulin-induced hypoglycemia in 10 normal volunteer subjects on two occasions--once after induction of asymptomatic nocturnal hypoglycemia and once after control studies in which saline rather than insulin was infused overnight. Compared with control experiments, asymptomatic nocturnal hypoglycemia increased the threshold (required greater hypoglycemia for initiation) and reduced the magnitude of autonomic and neuroglycopenic symptoms, counterregulatory hormone responses, and cognitive dysfunction during subsequent hypoglycemia (all, P < 0.05). These results indicate that asymptomatic hypoglycemia may induce hypoglycemia unawareness and, thus, may explain why not every patient with this condition has a history of prior hypoglycemia. Our results therefore support the concept that in type I diabetes this phenomenon may be largely attributable to antecedent hypoglycemia. PMID- 8349034 TI - Linkage analysis and molecular scanning of glucokinase gene in NIDDM families. AB - Mutations in the glucokinase gene are a major cause of maturity-onset diabetes of the young. To evaluate the contribution of this gene to the development of late onset NIDDM, linkage analyses between DNA polymorphisms at the glucokinase locus and NIDDM were performed in 79 multigenerational French families. In addition, all exons and the islet promoter region of glucokinase gene from 1 affected member from each family as well as from 17 unrelated women with previous gestational diabetes were amplified by polymerase chain reaction and screened for mutations by single-strand conformational polymorphism and DNA sequencing. Linkage of glucokinase and NIDDM was significantly rejected under all models tested. However, in 1 family, the lod score was 2.30, and we found a nucleotide substitution at the position -30 in the islet promoter region that cosegregated with diabetes. The proband of this family was a gestational diabetic individual. No other mutation in glucokinase was found in the 79 NIDDM families. We identified a missense mutation (TGG257-->CGG257) in exon 7 of glucokinase gene from 1 of 17 women with gestational diabetes, which was present in all diabetic members of her family. This family is likely to be a cryptic maturity-onset diabetes of the young, as 4 younger members, carrying this mutation, were subsequently found to be hyperglycemic. In conclusion, no evidence was obtained to incriminate glucokinase as a major gene for late age of onset NIDDM. Diabetic families with mutations in glucokinase must be carefully investigated, to differentiate cryptic maturity-onset diabetes of the young from late-onset NIDDM. Furthermore, pregnancy reveals diabetes in women carrying a glucokinase defect. PMID- 8349035 TI - Role of prostaglandin H2 as an endothelium-derived contracting factor in diabetic state. AB - This study investigated the possible involvement of prostaglandin H2, an acetylcholine-induced endothelium-derived contracting factor in rat aorta, in the development of abnormality of the vasculature in diabetes. Rings of thoracic aorta were prepared from control Wistar-Kyoto and STZ-induced diabetic rats to examine the changes in isometric tension. In 10(-7) M norepinephrine precontracted rings, acetylcholine induced relaxations, which were significantly impaired in diabetic rats. Inhibition of thromboxane A2-prostaglandin H2 receptors with ONO-3708 (10(-6) M) prevented the development of the impairment of relaxation in diabetic rats. Thromboxane A2 synthesis inhibition with OKY-046 (10(-5) M) did not affect the acetylcholine-induced relaxation in both control and diabetic rats. In aortic rings under resting tension, acetylcholine induced a contraction that was greater in diabetic than control rats, when the nitric oxide production was inhibited by NG-nitro-L-arginine methylester (10(-4) M). This acetylcholine-induced contraction was observed only in the rings with intact endothelium and was completely abolished by ONO-3708 (10(-6) M). The concentration of 6-keto-prostaglandin F1 alpha in the solution bathing diabetic rat aortic rings increased significantly after acetylcholine (10(-5) M) administration. Prostacyclin (10(-9)-10(-6) M) did not induce contractions at all. Prostacyclin is unlikely to mediate contractions because of its low contractile potency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349036 TI - Counterregulation during hypoglycemia is directed by widespread brain regions. AB - Previous studies have demonstrated the importance of the brain in directing counterregulation during insulin-induced hypoglycemia in dogs. The capability of selective carotid or vertebrobasilar hypoglycemia in triggering counterregulation was assessed in this study using overnight-fasted dogs. Insulin (21 pM.kg-1.min 1) was infused for 3 h to create peripheral hypoglycemia in the presence of 1) selective carotid hypoglycemia (vertebral glucose infusion, n = 5), 2) selective vertebrobasilar hypoglycemia (carotid glucose infusion, n = 5), 3) the absence of brain hypoglycemia (carotid and vertebral glucose infusion, n = 4), or 4) total brain hypoglycemia (no head glucose infusion, n = 5). Glucose was infused via a leg vein as needed in each group to minimize the differences in peripheral glucose levels (2.6 +/- 0.1, 3.0 +/- 0.2, 2.7 +/- 0.1, and 2.5 +/- 0.1 mM, respectively). The humoral responses (cortisol, glucagon, catecholamines, and pancreatic polypeptide) to hypoglycemia were minimally attenuated (< 40%) by selective carotid or vertebrobasilar euglycemia. In addition, the increase in hepatic glucose production, as assessed using [3-3H]glucose, was attenuated by only 41 and 34%, respectively, during selective carotid or vertebrobasilar hypoglycemia. These observations offer support for the hypothesis that more than one center is important in hypoglycemic counterregulation in the dog and that they are located in brain regions supplied by the carotid and vertebrobasilar arteries, because significant counterregulation occurred when hypoglycemia developed in either of these circulations. Counterregulation during hypoglycemia, therefore, is probably directed by widespread brain regions that contain glucose sensitive neurons such that the sensing sites are redundant. PMID- 8349037 TI - Insulin does not induce the hydrolysis of a glycosyl phosphatidylinositol in rat fetal hepatocytes. AB - An inositol phosphoglycan that is the polar head group of a glycosyl phosphatidylinositol has been considered as a putative mediator of insulin action. To gain insight into the functions of this hormone during development, the relationships between insulin, insulin receptors, glycosyl phosphatidylinositol, and inositol phosphoglycan were studied. Glycosyl phosphatidylinositol was isolated and characterized in fetal liver as early as day 15 of intrauterine life. In isolated hepatocytes from fetal and adult rats labeled with [3H]glucosamine, [3H]galactose, or [3H]myo-inositol, these molecules were incorporated into glycosyl phosphatidylinositol. In hepatocytes labeled with [3H]glucosamine and then allowed to react with [1-14C]IAI, the [3H]glycosyl phosphatidylinositol was purified as the 14C-labeled amidinated lipid. Glycosyl phosphatidylinositol molecules from fetal and adult cells were sensitive to hydrolysis by a phosphatidylinositol-specific phospholipase C from B. cereus. The product of this hydrolysis inhibits the activity of a cAMP-dependent protein kinase, whereas this effect was abolished by nitrous acid deamination. In isolated hepatocytes from adult animals, an inverse correlation between extracellular insulin and the number of insulin receptors and the cellular content of glycosyl phosphatidylinositol was observed. However, in fetal hepatocytes insulin failed to reduce the glycosyl-phosphatidylinositol content when labeled either with [1-14C]isethionyl acetimidate or [3H]glucosamine, whereas insulin-like growth factor I produced a significant hydrolysis of glycosyl phosphatidylinositol. Fetal and adult hepatocytes were incubated with insulin or inositol phosphoglycan after which glycogen phosphorylase activities were determined. Inositol phosphoglycan mimicked the action of insulin on both forms of the enzyme from adult hepatocytes, whereas in fetal cells insulin did not change, and purified inositol phosphoglycan reduced the activities of glycogen phosphorylase. These findings suggest a dissociation between insulin receptor occupancy and the expected hormonal effects in fetal hepatocytes. This could be related to alterations at a postreceptor level. PMID- 8349038 TI - Signals derived from glucose metabolism are required for glucose regulation of pancreatic islet GLUT2 mRNA and protein. AB - Pancreatic islet GLUT2 mRNA is known to be regulated in vitro and in vivo by glucose. We have investigated several potential mechanisms mediating the response of islet GLUT2 to glucose. GLUT2 mRNA and protein were measured from isolated rat islets cultured for up to 24 h under selected conditions. Glucose at 11 mM stimulated GLUT2 mRNA 10-fold compared with 2 mM glucose, with no additional increase at 16.7 mM glucose, whereas maximal 4-fold induction of the protein was attained with 16 mM glucose. Time course studies showed a 2.5-fold induction of GLUT2 mRNA apparent after only 8 h of culture at 16.7 mM glucose. Glycolysis inhibitor mannoheptulose suppressed the stimulatory effect of 16.7 mM glucose on GLUT2 mRNA and protein. Metabolizable sugars mannose and glyceraldehyde enhanced transporter mRNA levels, in contrast with the lack of stimulation by nonmetabolizable 2-deoxy-D-glucose. Stimulation by different sugars and glycolysis inhibition led to analogous changes of proinsulin mRNA, suggesting that common signaling mechanisms are shared in glucose regulation of proinsulin and GLUT2 gene expression. Preexposure to mannoheptulose, however, failed to suppress glucose-stimulated insulin release. Tunicamycin, a glycoprotein synthesis inhibitor, did not block the effect of 16 mM glucose on GLUT2 mRNA levels. RNA and protein synthesis inhibitors actinomycin and cycloheximide abolished the enhancing effects of high glucose on GLUT2 mRNA. These findings indicate that glucose metabolism, but not glycoprotein synthesis or substrate interaction with the transporter protein, is instrumental in the stimulatory effects of glucose on beta-cell GLUT2 mRNA accumulation. In addition, ongoing RNA and protein synthesis are required for this effect. PMID- 8349039 TI - Regulation of apolipoprotein A-I-containing lipoproteins in IDDM. AB - In IDDM patients, serum high-density lipoprotein cholesterol concentrations have been reported to be normal or elevated. The spectrum of high-density lipoprotein particles is highly heterogeneous, but no data are available on the subpopulations of high-density lipoprotein in IDDM. We, therefore, studied the spectrum of high-density lipoprotein particles in 86 IDDM patients (51 men and 35 women) 37 +/- 10 yr of age and in 74 sex-, age-, and body mass index-matched healthy nondiabetic subjects. The concentrations of high-density lipoprotein and HDL2 cholesterol were higher in the IDDM group than in the control subjects (P < 0.01). The apoA-I-to-apoA-II ratio was higher in the IDDM patients than in the nondiabetic subjects (P < 0.001) because of an increased concentration of LpA-I particles (61 +/- 17 vs. 53 +/- 15, P < 0.01). LpA-I particles correlated positively with high-density lipoprotein and HDL2 cholesterol in the two groups. Postheparin plasma lipoprotein lipase activity was significantly higher in the IDDM group than in the control group (P < 0.001), whereas postheparin plasma hepatic lipase activities were similar in both groups. Plasma cholesteryl ester transfer protein activity was estimated in an in vitro isotopic assay using exogenous labeled donor (low-density) and acceptor (high-density) lipoproteins in the absence of native lipoproteins. We observed no difference in cholesteryl ester transfer protein activity between the groups, and no significant correlations existed between cholesteryl ester transfer protein activity and high density lipoprotein subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349040 TI - Regulation of insulin-stimulated glycogen synthase activity by overexpression of glutamine: fructose-6-phosphate amidotransferase in rat-1 fibroblasts. AB - High glucose concentrations such as are seen in diabetes mellitus are known to have deleterious effects on cells, but the pathways by which glucose induces these effects are unknown. One hypothesis is that metabolism of glucose to glucosamine might be involved. For example, it has been shown that glucosamine is more potent than glucose in inducing insulin resistance in cultured adipocytes and in regulating the transcription of the growth factor transforming growth factor alpha in smooth muscle cells. The rate-limiting step in glucosamine synthesis is the conversion of fructose-6-phosphate to glucosamine-6-phosphate by the enzyme glutamine:fructose-6-phosphate amidotransferase. To test the hypothesis that this hexosamine biosynthesis pathway is involved in the induction of insulin resistance, we have overexpressed the enzyme glutamine:fructose-6 phosphate amidotransferase in Rat-1 fibroblasts and investigated its effects on insulin action in those cells. We electroporated Rat-1 fibroblasts with expression plasmids that did and did not contain the gene for glutamine:fructose 6-phosphate amidotransferase and measured glycogen synthase activity at varying insulin concentrations. Insulin stimulation was blunted in the glutamine:fructose 6-phosphate amidotransferase-transfected cells, resulting in decreased insulin sensitivity reflected by a rightward shift in the dose-response curve for activation of synthase (ED50 = 7.5 nM vs. 3.4 nM insulin, in glutamine:fructose-6 phosphate amidotransferase and control cells, respectively). Rat-1 fibroblasts incubated with 5.- mM glucosamine for 3 days exhibited a similar shift in the dose-response curve. The rightward shift in the dose-response curve is seen as early as 2 days after poration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349041 TI - Relationship of proinsulin and insulin to cardiovascular risk factors in nondiabetic subjects. AB - Recent data suggest that proinsulin is strongly associated with cardiovascular risk factors in diabetic subjects. However, this relationship has not been examined in nondiabetic subjects. Therefore, we examined the relation of proinsulin to lipids, obesity (body mass index), and waist-to-hip ratio in 260 nondiabetic individuals from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Proinsulin was measured by radioimmunoassay, and insulin was measured by a Linco radioimmunoassay that does not cross-react with proinsulin. Fasting insulin was significantly associated with body mass index (0.42), waist-to-hip ratio (r = 0.30), triglyceride (r = 0.29), high-density lipoprotein cholesterol (r = -0.20), and systolic blood pressure (r = 0.16) but not significantly related to diastolic blood pressure (r = 0.11). Fasting proinsulin was significantly associated with body mass index (r = 0.19), waist-to-hip ratio (r = 0.25), triglyceride (r = 0.41), systolic blood pressure (r = 0.19), and diastolic blood pressure (r = 0.15). Proinsulin was more strongly related to increased triglyceride than insulin despite its weaker relationship to obesity. In multivariate analyses, proinsulin continued to be significantly related to triglyceride concentrations (explaining 23.1% of the variance) and to systolic blood pressure (explaining 4.0% of the variance), even after adjusting for insulin. These observations suggest that proinsulin should be measured in addition to insulin in epidemiological studies. Proinsulin may be a marker for metabolic decompensation in prediabetic subjects. PMID- 8349042 TI - Pancreatic islet function in nondiabetic and diabetic BB rats. AB - A decreased acute insulin response to glucose in islet cell antibody positive humans predicts diabetes. Because the dominant mechanism leading to decreased in vivo acute insulin response to glucose remains unclear, perifused islets were examined before and after diabetes onset in BB rats to assess the role of glucose sensitivity on insulin secretion in individual islets. Islets from normal WF rats, diabetes-prone rats without inflamed islets, diabetes-prone rats with inflamed islets, and diabetic rats were studied at 2.0, 8.3, and 16.7 mM glucose. Immunoreactive insulin from WF islets at 16.7 mM glucose was 0.15 +/- 0.02 ng.0-7 min-1 x islet-1 for the first phase and 1.00 +/- 0.05 ng.7-20 min-1 x islet-1 for the second phase of biphasic secretion, compared with basal secretion of 0.10 +/- 0.03 ng.20 min-1 x islet-1 at 2 mM glucose. Diabetes-prone noninflamed islets showed a 0.20 +/- 0.03 ng first-phase secretion, a 1.32 +/- 0.13 ng second-phase secretion after 16.7 mM glucose, and 0.093 +/- 0.02 ng.20 min-1 x islet-1 at 2 mM glucose, indicating no intrinsic BB rat strain secretion abnormality. Diabetes prone inflamed islets had secretions of 0.35 +/- 0.02 ng during the first phase (P < 0.05 vs. WF) and 1.78 +/- 0.29 ng during the second phase (P < 0.05 vs. WF) after 16.7 mM glucose, with 0.24 +/- 0.08 ng.20 min-1 x islet-1 at 2 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349043 TI - Inositol glycan phosphate derived from human erythrocyte acetylcholinesterase glycolipid anchor and inositol cyclic 1,2-phosphate antagonize glucagon activation of glycogen phosphorylase. AB - In this study we examine the hypothesis that an inositol glycan phosphate can act similarly to insulin on intact cells. The inositol glycan phosphate used in this study (glycan alpha) was isolated previously from the glycoinositol phospholipid anchor of human erythrocyte acetylcholinesterase and was shown to have the structure glycine-ethanolamine-PO4-Man-Man-(N,N-dimethylethanolamine-PO4)Man- (N,N-dimethyl)GlcN-inositol-PO4. The cellular response investigated was the glucagon-stimulated activation of glycogen phosphorylase in rat hepatocytes. When hepatocytes were incubated with 20 nM glucagon for 4 min, the ratio of phosphorylase a activity to total phosphorylase increased from a basal value of 0.49 +/- 0.02 to 0.82 +/- 0.03 (mean +/- SE, n = 15). Inclusion of either 100 nM insulin or 3-10 microM glycan alpha during the glucagon incubation significantly decreased the glucagon-stimulated activity ratio to 0.74 +/- 0.03 for either agent. Furthermore, hepatocyte preparations differed in their response to insulin and were divided into insulin-responsive and -resistant groups. Glycan alpha had a significant effect only in the insulin-responsive group for which the observed activity ratio for 10 microM glycan alpha plus glucagon (0.68 +/- 0.05) compared closely with that for insulin plus glucagon (0.70 +/- 0.04). For the insulin resistant group, the activity ratio in the presence of 10 microM glycan alpha was 0.81 +/- 0.03, unchanged from the control with glucagon alone. Because glycan alpha contains an inositol phosphate group, the effect of inositol cyclic 1,2 phosphate on the glucagon-stimulated activity ratio was determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349044 TI - Insulin resistance and insulin secretion are determinants of oral glucose tolerance in normal individuals. AB - Plasma glucose values after oral glucose challenge vary widely in nondiabetic subjects. We have now evaluated the role of insulin resistance in determining the plasma glucose response to oral glucose in 74 volunteer subjects with normal glucose tolerance. In these subjects, we determined the plasma glucose and insulin responses over a 3-h period to a 75-g oral glucose challenge, and the steady-state plasma glucose concentration during a continuous infusion of somatostatin, glucose, and insulin (a quantitative measure of insulin resistance). The plasma glucose response was defined as the incremental increase in plasma glucose concentration above the fasting value for 3 h after the oral glucose challenge. Multiple regression analysis was used to define the relationship between the dependent variable (plasma glucose response) and various predictors of this response. These analyses indicated that both the steady-state plasma glucose and the incremental insulin response during the first 30 min after the glucose load were significant predictors of the plasma glucose response. In those individuals in whom insulin action was impaired and the 30-min plasma insulin response was decreased, plasma glucose values reached higher levels. When standardized regression coefficients were determined, the incremental glucose response was directly correlated with steady-state plasma glucose (r = 0.700, P < 0.001) and inversely with the insulin response during the first 30 min (r = 0.268, P = 0.023). Furthermore, the correlation between steady-state plasma glucose and glucose response was significantly greater (P < 0.005) than that between the glucose response and 30-min insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349045 TI - Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor. AB - Increased routing of glucose through the hexosamine-biosynthetic pathway has been implicated in the development of glucose-induced insulin resistance of glucose transport in cultured adipocytes. Because both glucosamine and glucose enter this pathway as glucosamine-6-phosphate, we examined the effects of preincubation with glucosamine in isolated rat diaphragms and in fibroblasts overexpressing the human insulin receptor (HIR-cells). In muscles, pre-exposure to glucosamine inhibited subsequent basal and, to a greater extent, insulin-stimulated glucose transport in a time- and dose-dependent manner and abolished the stimulation by insulin of glycogen synthesis. Insulin receptor number, activation of the insulin receptor tyrosine kinase in situ and after solubilization, and the total pool of glucose transporters (GLUT4) were unaffected, and glycogen synthase was activated by glucosamine pretreatment. In HIR-cells, which express GLUT1 and not GLUT4, basal and insulin-stimulated glucose transport were unaffected by glucosamine, but glycogen synthesis was markedly inhibited. Insulin-stimulated activation of protein kinases (MAP and S6) was unaffected, and the fractional velocity and apparent total activity of glycogen synthase was increased in glucosamine-treated HIR-cells. In pulse-labeling studies, addition of glucosamine during the chase prolonged processing of insulin proreceptors to receptors and altered the electrophoretic mobility of proreceptors and processed alpha-subunits, consistent with altered glycosylation. Glucosamine-induced insulin resistance of glucose transport appears to be restricted to GLUT4-expressing cells, i.e., skeletal muscle and adipocytes; it may reflect impaired translocation of GLUT4 to the plasmalemma. The glucosamine-induced imbalance in UDP sugars, i.e., increased UDP N-acetylhexosamines and decreased UDP-glucose, may alter glycosylation of critical proteins and limit the flux of glucose into glycogen. PMID- 8349046 TI - North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin. AB - In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk. PMID- 8349047 TI - Insulin resistance in spontaneously hypertensive rats. Difference in interpretation based on insulin infusion rate or on plasma insulin in glucose clamp studies. AB - Isotopic glucose turnover was measured during euglycemic glucose clamp studies in spontaneously hypertensive rats and normotensive Wistar-Kyoto control rats, under pentobarbital sodium anesthesia. At an insulin infusion rate of 4 mU.kg-1 x min 1, glucose disposal rate and hepatic glucose output were not significantly different in either group, at a plasma glucose of 6 mM. However, steady-state plasma insulin levels in spontaneously hypertensive rats were more than double those in Wistar-Kyoto rats (2.34 +/- 0.16 [mean +/- SE] vs. 6.78 +/- 0.58 nM, P < 0.00005, n = 7 in each group). Additional studies (n = 30 in spontaneously hypertensive rats and n = 32 in Wistar-Kyoto control rats) were conducted to match insulin levels in the two groups over a wide range, using infusion rates of 0.5-10 mU.kg-1 x min-1. When the responses of glucose disposal rate and hepatic glucose output to insulin were analyzed from the standpoint of plasma insulin levels, a highly significant difference was seen in the response to insulin between spontaneously hypertensive rats and Wistar-Kyoto rats, for both glucose disposal rate (P < 0.000005) and hepatic glucose output (P = 0.00007). The slope of the regression line for glucose disposal rate versus plasma insulin was lower in spontaneously hypertensive rats compared with Wistar-Kyoto rats (2.652 vs. 4.864, P < 0.001), indicating that insulin stimulation of glucose disposal rate was reduced by 50% in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349048 TI - No reason to regard a low number of bursts of muscle sympathetic nerve activity in IDDM as a sign of autonomic neuropathy. PMID- 8349049 TI - Corrigendum for limitations in the use of [2-14C]acetate for measuring gluconeogenesis in vivo. PMID- 8349051 TI - Teaching family medicine. PMID- 8349050 TI - Manuscript review in family medicine. PMID- 8349052 TI - Family medicine education: independent of specialists? PMID- 8349053 TI - Asserting our academic identity: diversity, quality, and scholarship. PMID- 8349054 TI - Identifying and communicating with patients who have poor literacy skills. PMID- 8349055 TI - Characteristics of strong departments of family medicine: results of a Delphi survey. AB - BACKGROUND: The establishment and support of strong university-based departments of family medicine is central to the success of family practice. The purpose of this study was to provide existing and developing departments of family medicine with information on the characteristics of strong established departments. METHODS: Chairs of existing departments were asked to identify the five strongest university-based departments in the country. Based on an 80% response rate, a select group of 24 chairs representing the strongest departments was surveyed using a Delphi technique. RESULTS: A systems and contingency model was used as the basis for organizing the Delphi responses. Seven core factors were identified and ranked by the chairs for each of the six systems and subsystems of the model describing university-based departments. CONCLUSIONS: Key ingredients that are common to most strong departments are the ability of the department to respond to the external environment, the presence of state and federal financial support, leadership and vision by the chair, strong clinically oriented faculty, management practices that keep everyone informed, and mutual support and respect within the department. PMID- 8349056 TI - Geriatric education and practice of family practice graduates: an alumni survey. AB - BACKGROUND: The goal of this research was to study the relationship between family practice residency training in geriatrics and subsequent postresidency geriatric practice patterns. METHODS: We surveyed all graduates of the University of Maryland Family Practice Residency Program through 1990 to determine their attitudes toward their geriatric training and the extent of their geriatric practice. Logistic regression analysis was used to identify factors associated with 1) making house calls, 2) making weekly nursing home visits, and 3) having a practice in which more than 25% of patients were older than age 65. RESULTS: The responses of 143 graduates were analyzed. Most respondents (58.8%) made house calls, and the majority (51%) saw nursing home patients weekly. Older respondents and those possessing Certificates of Added Qualifications in Geriatric Medicine (CAQGMs) were more likely to treat patients older than age 65. Respondents with larger nursing home practices rated their geriatric training more favorably. Multivariate logistic regression analysis found that the following factors were associated with making house calls: working in a group family practice (odds ratio [OR] = 3.88, 95% confidence interval [CI] = 2.58-5.84) and a rural practice location (OR = 2.71, 95% CI = 1.77-4.17). Physicians who had additional training after residency (OR = 0.16, 95% CI = 0.10-0.25) were less likely to make house calls. Factors associated with making weekly nursing home visits were: additional training after residency (OR = 0.31, 95% CI = 0.19-0.50) and working in a group family practice (OR = 2.43, 95% CI = 1.63-3.65). Attainment of a CAQGM was the only factor associated with having more than 25% geriatric patients in the office practice (OR = 6.00, 95% CI = 2.72-13.24). CONCLUSIONS: Most graduates of the University of Maryland Family Practice Residency Program maintain significant geriatric practices and value geriatric training, but whether favorable training experiences influence graduates' practices is unknown. Prospective studies of family practice residents are needed to clarify the influence of geriatric curricula on residents' future clinical practices. PMID- 8349057 TI - The family practice elective that saved two doctors. PMID- 8349058 TI - Satisfactions and dissatisfactions of graduating family practice residents. AB - BACKGROUND: This study was conducted to determine whether the types of professional satisfactions and dissatisfactions experienced by family practice residents in one program were characteristic of those experienced by residents from other programs. METHODS: Materials and procedures developed previously were used in a study of 23 residents from five family medicine programs. Respondents were interviewed in the spring of their graduation year. Transcripts of these interviews were examined for the presence of specific themes relating to professional satisfactions and dissatisfactions. RESULTS: Themes found in the interviews from all five programs were similar to each other and to the themes uncovered previously. Satisfactions were related to the interpersonal aspects of patient care, the intellectual aspects of medicine, the process of delivering care, and instances of intervention in critical situations. An additional source of satisfaction, not found previously, was derived from activities in certain specific content areas of family medicine. Dissatisfactions reflected concerns about the bureaucratic climate in which medicine is currently practiced, time demands of a medical career, frustrations with patient behavior, and negative feelings about the professional situation of the family practice resident. CONCLUSIONS: Having corroborated the existence of satisfaction and dissatisfaction themes found earlier, results of this research may provide information to educators about the professional identity of the family physicians they are training. PMID- 8349059 TI - Criteria for evaluating performance of third-year medical students. AB - BACKGROUND: Evaluating medical student performance in clinical settings is an aspect of teaching that educators sometimes find difficult. This study was conducted to determine evaluation criteria for clinical performance that were considered important by physician faculty. These criteria were subsequently used in the student evaluation process for a decentralized clerkship in family medicine. METHODS: In Phase I, physician faculty were surveyed to identify preferred criteria for evaluating student performance through an open-ended format. In Phase II, the identified items were refined. In Phase III, 45 items were presented to the faculty for rating importance on a visual analogue scale. RESULTS: Twenty-nine of 31 physicians responded. Factor analysis identified three factors that accounted for 76.6% of the variance: application of knowledge, relationship with patients, and therapeutics in family medicine. CONCLUSIONS: Results of the study suggest that physician faculty have internalized expectations of clinical competence in the discipline of family medicine that address the basic dimensions of cognitive ability, problem-solving skills, and interpersonal relationships. PMID- 8349060 TI - Rapid estimate of adult literacy in medicine: a shortened screening instrument. AB - BACKGROUND: This study was conducted to validate a shortened version of the Rapid Estimate of Adult Literacy in Medicine (REALM). This screening instrument is designed to be used in public health and primary care settings to identify patients with low reading levels. It provides reading grade estimates for patients who read below a ninth-grade level. The REALM can be administered in one to two minutes by personnel with minimal training. METHODS: Two hundred and three patients in four university hospital clinics (internal medicine, family practice, ambulatory care, and obstetrics/gynecology) were given the REALM and three other standardized reading tests: the reading recognition section of the Peabody Individual Achievement Test-Revised (PIAT-R), the Wide Range Achievement Test Revised (WRAT-R), and the Slosson Oral Reading Test-Revised (SORT-R). One hundred inmates at a state prison were also given the REALM twice, one week apart, to determine test-retest reliability. RESULTS: The REALM correlated well with the three other tests. (Correlation coefficients were 0.97 [PIAT-R], 0.96 [SORT-R], and 0.88 [WRAT-R].) All correlations were significant at P < .0001. Test-retest reliability was 0.99 (P < .001). CONCLUSIONS: The REALM provides an estimate of patient reading ability, displays excellent concurrent validity with standardized reading tests, and is a practical instrument for busy primary care settings. PMID- 8349061 TI - Abdominal obesity is associated with insulin resistance. AB - BACKGROUND: Recent evidence suggests that insulin resistance and hyperinsulinemia may account for many of the medical complications of obesity. This study was performed to determine whether a predominance of body fat in the abdominal region is associated with insulin resistance and hyperinsulinemia. METHODS: Two groups of nine obese women were matched for age and total obesity but differed significantly in the pattern of fat distribution as defined by the waist-to-hip circumference ratio (WHR). The high-WHR group had a WHR of 0.87 (+/- 0.01), and the low-WHR group had WHR of 0.77 (+/- 0.02) (P < .05). RESULTS: Plasma levels of glucose, free fatty acids, and insulin, measured hourly for eight hours while the subjects consumed a diet of regular food, were higher in the high-WHR group. CONCLUSION: The high-WHR group (abdominal obesity) was more resistant to the action of insulin. These results suggest that measurement of the WHR could help define the degree of medical risk for a given obese patient seeking treatment. PMID- 8349062 TI - Do family physicians treat obese patients? AB - BACKGROUND: The purpose of this study was to characterize what patient and physician factors increase the likelihood of physicians counseling weight loss in their overweight patients. METHODS: A retrospective chart survey of 418 outpatient charts from 50 family medicine residents and faculty was conducted. RESULTS: Of the 267 patients who were overweight based on a body mass index score of more than 27, only 29.6% had been instructed to lose weight. Overweight patients with hypertension, diabetes, hypercholesterolemia, or coronary artery disease were instructed to lose weight 32.9% of the time. Patient age or sex and physician age, sex, or level of training did not affect the frequency of treatment. CONCLUSION: Physicians need to be more aggressive in their counseling of overweight patients. PMID- 8349063 TI - Comparative cytologic yield and quality of three Pap smear instruments. AB - BACKGROUND: Various sampling techniques of the cervix have established false negative rates ranging from 18% to 45%. A number of studies suggest that this false negative rate can be reduced by sampling techniques that are associated with higher yields of endocervical cells. METHOD: This study enrolled 301 women, each of whom had a Pap smear obtained using three different sampling instruments (a cervical brush, a plastic spatula, and a cotton swab) in random order. RESULTS: The cervical brush yielded a better endocervical sample than either of the other instruments (P < .001), and there was no difference between the swab and spatula. In addition, the recovery of endocervical cells increased with each additional sample taken, regardless of instrument used (P < .001), although the difference in yield between the second and third samples was not significant. CONCLUSIONS: To enhance the yield of endocervical cells in Pap smear sampling, consideration should be given to using the cervical brush routinely as a sampling instrument and to taking more than one sample per screening. PMID- 8349064 TI - [Inhibitors of proton pump, a new target: the visible vessel]. PMID- 8349065 TI - [Use of an electronic barostat for measurement of motor response of the proximal stomach to feeding and different nervous stimuli in man]. AB - Electronic barostat allows to measure volume variations of an intragastric air filled bag maintained at a low constant pressure level, reflecting gastric tone variations. The aims of the present study were to record physiologic variations of gastric tone in humans a) in the fasting state, with and without different stimuli, and b) in the fed state. The bag was placed into the proximal stomach of healthy subjects and connected to the barostat. Volume variations were recorded in the basal state and in response to a) a balanced liquid meal (200 mL, 200 kcal, n = 8), b) sham feeding and sham feeding after cholinergic blockade (atropine 10 micrograms.kg-1 IV, n = 8), and c) graded antroduodenal distensions performed with a tandem balloon (n = 6). During fasting, the proximal stomach presented both a tonic and an intermittent phasic motor pattern (volume waves of 1.2 min maximal period). Meal ingestion was rapidly followed by a dramatic fall in proximal gastric tone (> 200% of preprandial volume within 11 +/- 5 min). After a meal, the intragastric bag returned to preprandial volume after 92 +/- 12 min (ranges: 75-110). Proximal gastric tone was not significantly modified by atropine or by sham feeding alone or after atropine. Antroduodenal distensions reproducibly induced volume dependent relaxations (r = 0.98, P < 0.001) with inhibition of the phasic activity. These results confirm the value of electronic barostat for the measurement of proximal gastric tone, and show that postprandial relaxation is not masked by a low volume liquid meal. Sham feeding does not appear to be an adequate stimulus to induce gastric relaxation. This suggests that vagal fibers involved in gastric relaxation are not the same (or have a higher stimulation threshold) than fibers involved in cephalic phase of gastric secretion. PMID- 8349066 TI - Orally administered omeprazole versus injection therapy in the prevention of rebleeding from peptic ulcer with visible vessel. A multicenter randomized study. AB - Endoscopic injection therapy significantly reduces the risk of bleeding relapse in patients with digestive hemorrhage due to peptic ulcers associated with a visible vessel. Profound and sustained acid inhibition by proton pump inhibitors may generate optimal conditions for clotting and prevent bleeding relapse. Over a one-year period, 52 patients presenting with digestive hemorrhage, in whom emergency endoscopy showed a peptic ulcer with a non-bleeding visible vessel, were enrolled in a multicenter randomized study comparing oral omeprazole, 40 mg per day (n = 31) vs adrenaline (1:10,000) plus polidocanol (1%) injection associated with oral ranitidine 300 mg per day (n = 21). Rebleeding occurred in 15/52 (29%) patients: 8/31 (26%) in the omeprazole group with 6 major hemorrhages (19%), and in 7/21 (33%) in the injection group with 3 major hemorrhages (14%); the differences were not significant. No difference was observed between omeprazole and injection group in terms of volume of transfused blood (2.03 +/- 1.5 vs 3.1 +/- 0.9 blood units), need for hemostatic surgery (9.6% vs 14.3%), mortality (19.3% vs 14.3%) and mean hospital stay (11.5 days both groups). This study suggests that oral omeprazole, 40 mg per day, has an efficacy comparable to injection therapy in reducing the bleeding relapse from non bleeding peptic ulcers associated with visible vessel. PMID- 8349067 TI - [Comparison of lansoprazole (30 mg) and omeprazole (20 mg) in the treatment of duodenal ulcer. A multicenter double-blind comparative trial]. AB - The efficacy of lansoprazole (30 mg/d) and omeprazole (20 mg/d) has been assessed in active duodenal ulcer disease in 144 patients included in a multicentric, randomized, double-blind trial. After two weeks, the healing rates were 74% and 58% in the lansoprazole and omeprazole groups, respectively (P = 0.049). After 4 weeks, the healing rates were 94% in each group (NS). The delay to pain relief was 2 days for lansoprazole and 3 days for omeprazole (NS). Minor side effects occurred in 12% of the lansoprazole treated patients and in 13% of the omeprazole treated patients. No severe adverse events were reported. A slight increase in serum gastrin level was observed, similar in both groups (+35 UI/L and +19 UI/L for lansoprazole and omeprazole respectively). This study confirms previous results concerning the efficacy of both treatments in duodenal ulcer disease. The statistical difference observed for healing rates after 2 weeks could correspond to a faster efficacy for lansoprazole (30 mg) than for omeprazole (20 mg). PMID- 8349068 TI - [Diagnostic modalities and treatment of cancer of the pancreas. Evolution in the population in the department of Cote d'Or from 1976 to 1988]. AB - There is no study establishing time trends for the diagnostic and therapeutic approaches to pancreatic cancer based on population data. The data of the Registry of Digestive Tumors of Cote-d'Or (France) were used to this end in 544 cancers diagnosed between 1976 and 1988. The proportion of the histologically confirmed cases increased annually by 13.4% (P < 0.001). This was mainly due to progress in percutaneous biopsy (+25.7% per year between 1983 and 1988, P < 0.001). As regards the diagnosis, ultrasonography was used more frequently (+21.9% per year, P < 0.001) as well as CT scan since its introduction in 1983 (+19.6% per year, P < 0.001). Pancreatic cancer was diagnosed by sonography in 16.7% of the cases in 1976 and 70.6% in 1988 (mean annual variation: +5.7%, P < 0.001). The proportions for CT scan were 12.8% in 1983 and 23.5% in 1988 (mean annual variation: +3.5%, NS). There was no significant change in the use of retrograde cholangiopancreatography over time. Other diagnosis criteria were less frequently used: laparoscopy was no longer used after 1983 and intraoperative diagnosis was made less frequently (-2.5% per year, P < 0.001). Endoscopy or radiographic data were rarely used as a diagnosis criterion. These changes in approaches to the diagnosis of pancreatic cancer were not accompanied by any progress in diagnosis stage, therapeutic approach or survival suggesting that when clinical symptoms become evident, pancreatic cancer is already advanced. Therapeutic advances, early diagnosis in patient at risk or identification or reasons for pancreatic cancer are the only means of progress in this problem. PMID- 8349069 TI - A multifunction and programmable computerized barostat. AB - A new computerized barostat allowing digestive tone measurement but also programmed distensions is described. The apparatus consists of a pump, driven by a computer, which injects or aspirates air in a flacid bag placed in a part of the gastrointestinal tract when relaxation or contraction occurs. Several parameters can be programmed for tone measurement: mean pressure, window pressure and air flow rate. Isovolumic or isobaric distensions can be performed using three modes: linear, stepwise or step by step with intermediate deflation. The height (mL or mmHg) of the steps and the duration of the distensions and the deflations can also be programmed. Three automatic and one manual safety systems are included. In comparison with previously described barostats the main feature of this apparatus is that it is entirely computerized and can be used for programmed distensions. PMID- 8349070 TI - [Artificial nutrition and Crohn disease]. PMID- 8349071 TI - [Liver regeneration]. PMID- 8349073 TI - [Evolution of delta bilirubin/conjugated bilirubins ratio in serum after live transplantation]. AB - Serum delta-bilirubin measured in relationship to total bilirubin could be a liver function test in hepatobiliary diseases and even a marker of early rejection after liver transplantation. Delta-bilirubin bound to albumin constitutes with mono and diglucuroconjugates, conjugated bilirubins. We determined the delta-bilirubin/conjugated bilirubins ratio and studied its value in various complications in 16 liver recipients. The results were compared with alanine aminotransferase activity and prothrombin index. Hyperbilirubinemia and a delta-bilirubin/conjugated bilirubins ratio lower than 40% were observed initially. After 15 days, the delta-bilirubin/conjugated bilirubins ratio evolved differently according to the functional state of the graft, which allowed to distinguish three patient groups: in patients with good graft function, the ratio increased regularly to reach 65% or more on the 30th day; in patients with dysfunctional episodes, the ratio was always less than or equal to 40% and did not increase after the 15th day; in other patients, the ratio was lower than 40% and dropped suddenly before death. After liver transplantation, the delta bilirubin/conjugated bilirubins ratio may be a simple liver function marker. Alone, however, it cannot be used to assess acute rejection. PMID- 8349072 TI - [Decrease of haptoglobin serum level in patients with chronic viral hepatitis C]. AB - Serum levels of haptoglobin, an acute phase protein, in usually increased in patients with inflammation and decreased in patients with intravascular hemolysis. Changes in haptoglobin serum levels were also observed in patients with liver disease. The aim of this study was to evaluate the serum level of haptoglobin in patients with chronic viral hepatitis C. Haptoglobin serum levels were measured by rate nephelometry in 34 patients with histologically proven chronic viral hepatitis C and in 30 controls. Haptoglobin serum levels were lower in patients than in controls (0.56 +/- 0.36 versus 0.90 +/- 0.35 g/L, P < 0.001). In patients with chronic hepatitis but without cirrhosis, haptoglobin serum levels were decreased as well. Haptoglobin serum levels were positively correlated to prothrombin index (P < 0.001) and negatively correlated to the histology activity index of Knodell (P < 0.001), and especially to scores of fibrosis (P < 0.001) and periportal necrosis (P < 0.05). Red cell count, indirect bilirubin level, and reticulocyte count, as markers of hemolysis, were similar in patients and controls. We conclude that determination of haptoglobin serum levels may be useful in the evaluation and the follow-up of patients with chronic viral hepatitis C. PMID- 8349074 TI - [Hepatocyte regeneration]. PMID- 8349076 TI - [Primary sclerosing cholangitis and autoimmune cochlear deafness: a new syndrome?]. AB - Association of autoimmune cochlear hearing loss with primary sclerosing cholangitis is reported in two patients. Endocochlear sensorineural hearing loss was associated with the presence of anti-cochlear antibodies in the serum directed against the walls of vessels in the stria vascularis. The hearing loss appeared at the same time or shortly after the diagnosis of cholangitis. This association, which has never been described, may reinforce the theory of the role of immunologic factors in the pathogenesis of primary sclerosing cholangitis, possibly linked to or initiated by vasculitis. PMID- 8349075 TI - [Churg-Strauss syndrome with rectal localization and exudative enteropathy]. AB - The authors report the case of a 61-year old patient with a Churg-Strauss syndrome revealed by abdominal pain. Investigations showed a diffuse inflammatory digestive tract involvement, documented by endoscopy associated with protein losing enteropathy. Deep rectal biopsy revealed vasculitis in an otherwise macroscopically normal rectum. Faced with acute and life-threatening course of disease, emergency medical treatment with steroids and cyclophosphamide led to rapid regression of clinical, biological and radiological abnormalities. PMID- 8349077 TI - [Reflexions on the diagnosis and treatment of common bile duct lithiasis at the time of laparoscopic surgery]. PMID- 8349078 TI - [Liver abscess after endoscopic sclerotherapy of hemorrhagic stomach ulcer]. PMID- 8349079 TI - ["Papillomatosis" or "adenomatosis" of the Wirsung duct]. PMID- 8349080 TI - [Sweet's syndrome revealing colonic cancer]. PMID- 8349081 TI - [Sic transit]. PMID- 8349082 TI - [Diarrhea syndrome associated with the presence of Cyanobacterium-like bodies]. PMID- 8349083 TI - [Prevention of hemorrhagic recurrences from rupture of esophageal varices by elastic ligations. Preliminary study]. PMID- 8349084 TI - [Disclosure of autoimmune hepatitis by interferon]. PMID- 8349085 TI - [Acute cytolytic hepatitis caused by amoxapine]. PMID- 8349086 TI - [Acute hepatitis during treatment with fluoxetine]. PMID- 8349087 TI - [Place of endorectal ultrasound endoscopy in the preoperative evaluation of villous tumors]. PMID- 8349088 TI - [Colonoscopic screening in first degree relatives of patients with colorectal cancer]. PMID- 8349089 TI - A rapid method for preparation of rough and smooth lipopolysaccharide from Bacteroides, Porphyromonas and Prevotella. AB - We describe a new method for lipopolysaccharide (LPS) preparation by water extraction at 100 degrees C and subsequent digestion with proteinase K. The crude LPS could be reliably used for immunoblotting since it retained a high level of antigenicity, and was free of SDS and proteinase K, both of which can cause problems. Two monoclonal antibodies which failed to react with LPS prepared by two conventional methods reacted well with our preparation. We used the new method to prepare LPS from 44 strains of bacteria formerly classified as Bacteroides, some of which have been reclassified as Porphyromonas or Prevotella. In general, yields were good, and electrophoretic profiles obtained with SDS-PAGE and silver staining enabled strains to be rated rough, semi-rough, or smooth. PMID- 8349090 TI - Neisseria meningitidis transferrin-binding protein 1 expressed in Escherichia coli is surface exposed and binds human transferrin. AB - A gene library of Neisseria meningitidis B15 P1.16 DNA was established in lambda Zap II and clones containing DNA encoding transferrin binding protein 1 (TBP-1) identified following hybridisation with a 63-bp DNA probe based on the codon assignment for the first 21 N-terminal amino acids of TBP-1. Sequencing of the cloned DNA demonstrated that all of the intergenic DNA (i.e. upstream of tbp-1 running through to the 3' end of the transferrin-binding protein 2 gene) and approx. 15% of tbp-1 had been cloned. The complete gene was generated using a polymerase chain reaction, with the primer for the 3' end being based on tbp-A of N. gonorrhoeae, and the approx. 2.9-kb DNA product cloned into pGem-3Z. The expressed protein (approx. 100 kDa) reacted with antiserum to an N-terminal peptide of TBP-1. In addition, the native product was surface-expressed by Escherichia coli and bound human transferrin. PMID- 8349091 TI - Effect of anti-TNF-alpha treatment in an antibiotic treated murine model of shock due to Streptococcus pyogenes. AB - Experimentally, Gram-negative septic shock can be prevented by the prophylactic use of an anti-TNF-alpha monoclonal antibody. The clinical similarity between Gram-negative and Gram-positive septic shock suggested that anti-TNF-alpha therapy might have a wide application. Increased levels of TNF-alpha were seen in a murine model of septic shock due to Streptococcus pyogenes but administration of an anti-TNF-alpha monoclonal antibody had no beneficial effect on the outcome. PMID- 8349092 TI - Alcohol dehydrogenase (ADH2) from a mutant strain of Candida guilliermondii A80 03: purification and characterization. AB - Alcohol dehydrogenase ADH2 was purified twice from Candida guilliermondii strain A80-03, by ion exchange column chromatography on DEAE-Toyopearl 650M. The enzyme was a dimer of M(r) 98,500. ADH2 had a broad substrate specificity, oxidizing secondary alcohols as well as primary alcohols. The enzyme was sensitive to several inhibitors, such as metal chelators and thiol reagents. Kinetic studies suggested that ADH2 oxidized ethanol by an iso ordered sequential mechanism. PMID- 8349093 TI - Degradation of meta-trifluoromethylbenzoate by sequential microbial and photochemical treatments. AB - m- and p-trifluoromethyl (TFM)-benzoates are incompletely degraded by aerobic bacteria that catabolize alkylbenzoates; biodegradation ceases after ring-fission with the accumulation of a trifluoromethyl muconate semialdehyde (2-hydroxy-6-oxo 7,7,7-trifluorohepta-2,4-dienoate, TFHOD) which is resistant to biochemical attack. A bacterium (Strain V-1), isolated from sea-water, grew aerobically on benzoate or m-toluate. Cells grown on benzoate or m-toluate oxidized both compounds at similar relative rates. Catabolism involved benzoate 1,2-dioxygenase (decarboxylating) and meta-cleavage to yield muconate semialdehydes. Cells grown on benzoate metabolized m-TFM-benzoate to TFHOD. The ring-fission products from m toluate and TFHOD were degraded by sunlight, and equimolar fluoride was released from TFHOD. Sequential biochemical and photochemical treatment allowed the destruction of m-TFM-benzoate beyond the biochemically recalcitrant intermediate TFHOD. PMID- 8349094 TI - Eimeria refractile body proteins contain two potentially functional characteristics: transhydrogenase and carbohydrate transport. AB - cDNA encoding an immunogenic protein from partially sporulated oocysts of Eimeria acervulina was cloned and used to search for the homologous counterpart in Eimeria tenella. Monospecific antibodies were raised against the recombinant expression product. Using these antibodies, the parasite proteins were found to be localised in the refractile bodies. The derived amino-acid sequences were compared by computer using the SWISSPROT protein database. In addition to high homology between the Eimeria species, extensive similarity was found with pyridine nucleotide transhydrogenase from Escherichia coli. Comparison with the sugar signature database also resulted in a possible sugar binding domain present only in the Eimeria proteins. It is possible that the corresponding parasite proteins play a role in the recently discovered mannitol cycle of Eimeria. PMID- 8349095 TI - luxAB gene fusions with the arsenic and cadmium resistance operons of Staphylococcus aureus plasmid pI258. AB - pC101, a novel shuttle vector between Escherichia coli and Staphylococcus aureus carrying the lux genes encoding luciferase from Vibrio harveyi, selectable ampicillin and chloramphenicol markers and origins of replication for Gram negative and Gram-positive bacteria has been constructed. The inducibility of the arsenic and cadmium operon from S. aureus plasmid pI258 to different ions has been tested in E. coli and in S. aureus with two fusions in pC101: an arsB-luxAB and a cadA-luxAB transcriptional gene fusion. Patterns of induction are influenced by the host strain and are slightly different from previous reports using the blaZ gene as reporter gene. PMID- 8349096 TI - The biosynthetic genes for clavulanic acid and cephamycin production occur as a 'super-cluster' in three Streptomyces. AB - The cosmid cloning vector pHC79 has been used to clone fragments of chromosomal DNA from the Streptomyces: S. clavuligerus, S. jumonjinensis and S. katsurahamanus. These strains all produce both the beta-lactam antibiotic, cephamycin and the beta-lactamase inhibitor, clavulanic acid. Although structurally related these two beta-lactams are known to be derived from different biosynthetic precursors. Hybridisation studies and restriction mapping have shown that the gene clusters encoding the two biosynthetic pathways are chromosomally adjacent in these strains, thus creating a 'super-cluster' of genes involved in both the production and enhancement of activity of a beta-lactam antibiotic. PMID- 8349097 TI - Distribution in the genus Streptomyces of a homolog to nusG, a gene encoding a transcriptional antiterminator. AB - The presence of the vbrA gene encoding the transcriptional antiterminator NusG equivalent protein of Streptomyces virginiae was tested for in 73 Streptomyces species by Southern hybridization. Fifty-five strains (75%) including S. griseus, S. lividans TK-21 and S. coelicolor A3(2) showed clear hybridization signals, indicating wide distribution of vbrA or vbrA homologs in Streptomyces species. With hybridization patterns against 3 different probes, i.e., probes covering vbrA alone, the downstream gene rplK alone, and both vbrA-rplK, the 55 strains were classified into 4 groups. In the groups I, II and III (total 50 strains) vbrA was found to be adjacent to rplK, indicating that the gene arrangement vbrA rplK is common in Streptomyces and that these genes may constitute a part of gene cluster encoding several components of the transcription and translation apparatus, as in Escherichia coli. PMID- 8349098 TI - Variance components/major locus likelihood approximation for quantitative, polychotomous, and multivariate data. AB - Pearson [Philos Trans R Soc Lond [A] 200:1-66, 1903], Mendell and Elston [Biometrics 30:41-57, 1974], and Rice et al. [Biometrics 35:451-459, 1979] approximated the likelihood of the multifactorial model on a dichotomous phenotype by a procedure of successive univariate computation and conditioning. Hasstedt [Pap: Pedigree Analysis Package, Rev. 3. 1989] and Demenais [Am J Hum Genet 49:773-785, 1991] extended the algorithm to include a major locus. Here I extend the algorithm to polychotomous, quantitative, and multivariate phenotypes, add a major locus to the model, and describe and evaluate the accuracy of an approximation of the resulting variance components/major locus model. PMID- 8349099 TI - Inheritance of plasma apolipoprotein B levels in families of patients undergoing coronary arteriography at an early age. AB - An elevated plasma level of apolipoprotein B (apoB), the major protein of low density lipoproteins, is a risk factor for coronary artery disease. This study tested the hypothesis, suggested by previous studies, that the apoB level is strongly influenced by a major gene. The study population included 832 family members of 116 subjects who had undergone elective coronary arteriography at an early age. The apoB level was adjusted for age, gender, body mass index, alcohol consumption, and cigarette smoking (R2 = 20%). ApoB levels revealed strong familial aggregation with correlations among spouses of 0.23, parent-offspring of 0.16, and siblings of 0.21. Regressive models were used to examine inter individual variation in adjusted apoB levels. In the total sample, familial aggregation of the apoB level was consistent with two models: (1) a major gene model and (2) a polygenic model with a mixture of non-transmitted "types". Comparison of these two models in each family showed that 57 families supported the first model over the second. Segregation analysis in these 57 families conclusively favored a major gene model with codominant transmission. Genotypic means were 124, 164, and 208 mg/dl with relative frequencies of 45%, 44%, and 11%. Linkage studies in these families can be used to clarify the molecular basis of apoB regulation. However, in the whole population the genetic control of apoB levels may be quite complex. PMID- 8349100 TI - Segregation analysis of autosomal dominant polycystic kidney disease. AB - The results of classical segregation analysis on 159 families with polycystic kidney disease (PKD) are presented. It had been previously estimated that about 95% of autosomal dominant PKD (ADPKD) families have PKD1, the gene localized to chromosome 16p. The main purpose of the study was to determine if PKD shows any segregation distortion and to obtain new estimates of the age-dependent penetrance. Penetrance at the early ages of onset has increased during the last decade, presumably because of improvements in renal imaging and consequent earlier age of diagnosis. In the current study, the mean age of diagnosis was estimated to be 20 years, with a standard deviation (SD) of 15.94. Under the best fitting model (autosomal dominant), over 70% penetrance was estimated by age 30 years, over 95% by 50 years, and 99% by 55 years. Thus, diagnosis of this disease at an early age is possible without total reliance on DNA typing. The segregation ratio defined through the transmission probability in our model was not significantly different from 0.50, but its confidence limits were broad: 0.36 to 0.64. Neither transmission probability nor penetrance was significantly influenced by gender. The mutation rate was estimated to be 6.9 x 10(-5), in accordance with the previously observed high mutation rate for PKD. However, the mutation rate in our study may be overestimated because it neglects low penetrance alleles and phenocopies. PMID- 8349101 TI - Genetic analysis of drinking behavior in World War II veteran twins. AB - The objective of the present study was to investigate longitudinal changes in drinking behaviors of adult male twins and model these changes as a function of genetic and environmental influences. Alcohol data available for World War II veteran twins, first surveyed in 1967-69 and followed up during 1983-85, were used to examine components of variability in measures of alcohol consumption. Multivariate biometric analysis of these data indicated 1) longitudinal stability of drinking behaviors in this cohort, 2) a significant contribution of genetic factors to the observed stability that accounted for more than 80% of the stable variation in frequency and in quantity of alcohol consumed per drinking occasion, and 3) evidence for a significant contribution of shared environmental influences to drinking of specific beverages (e.g., wine). The implications of these results for issues of health in the elderly are considered. PMID- 8349102 TI - MORGAN's hypothesis of the genetic control of development. PMID- 8349103 TI - Isolation and characterization of SGE1: a yeast gene that partially suppresses the gal11 mutation in multiple copies. AB - Recessive mutations of GAL11 in Saccharomyces cerevisiae cause pleiotropic defects that include weak fermentation of galactose, alpha-specific sterility and slow growth on nonfermentable carbon sources. Recent experiments suggest that Gal11P functions as a "co-activator" that links transcriptional activators, such as Gal4p and Grf1p/Rap1p/Tuf1p, with the basic transcription machinery. In the present experiments we isolated a gene, SGE1, that suppresses gal11 for growth on ethidium bromide/galactose agar when the gene was present in two or more copies. The other gal11 phenotypes were not suppressed by SGE1 in the multiple-copy state. Multiple copies of SGE1 increased expression of galactose-inducible genes in gal11 yeast, presumably at the level of transcription. When SGE1 was disrupted in wild-type yeast, the expression of galactose-inducible genes decreased to 50 60% of the wild-type level, presumably due to effect on transcription. Complete DNA sequence analysis revealed that SGE1 encodes a predicted protein of 543 amino acids. SGE1-specific mRNA of 1.8 kilonucleotides was detected by Northern analysis along the direction of the open reading frame. The gene mapped near RAD56, at the right end of chromosome 16. PMID- 8349104 TI - TSF1 to TSF6, required for silencing the Saccharomyces cerevisiae GAL genes, are global regulatory genes. AB - The Saccharomyces cerevisiae GAL1 and GAL10 genes are controlled in response to the availability of galactose and glucose by multiple activating and repressing proteins bound at adjacent or overlapping sites in UASG. Negative control elements in UASG, designated GAL operators GALO1 to GALO6, are required to silence basal level transcription of GAL1 and GAL10 when galactose is absent. We isolated and characterized recessive mutations in six nuclear genes, TSF1 to TSF6, that impair silencing of GAL1 and GAL10 gene expression. Surprisingly, the results of several experiments suggest that the TSF genes encode global regulatory factors. tsf1 to tsf6 mutations derepressed expression from yeast CYC GAL hybrid promoters (fused to lacZ) that harbor a variety of operator sequences, and caused pleiotropic defects in cell growth, mating, and sporulation. S1 mapping and Northern blot results for tsf3 suggest that the molecular defect is at the transcriptional level. Mutant phenotypes were additive in certain combinations of tsf double mutants, implying that more than one silencing pathway is involved in TSF1 to TSF6 function. Most significantly, mutations in all six TSF1 to TSF6 genes activated expression from GAL1 and CYC1 promoters (fused to lacZ) lacking upstream activating sequences. Combined, the simplest interpretation of these results is that TSF1 to TSF6 encode factors that control the function of the basic RNA polymerase II transcriptional machinery. PMID- 8349105 TI - Isogenic strain construction and gene mapping in Candida albicans. AB - Genetic manipulation of Candida albicans is constrained by its diploid genome and asexual life cycle. Recessive mutations are not expressed when heterozygous and undesired mutations introduced in the course of random mutagenesis cannot be removed by genetic back-crossing. To circumvent these problems, we developed a genotypic screen that permitted identification of a heterozygous recessive mutation at the URA3 locus. The mutation was introduced by targeted mutagenesis, homologous integration of transforming DNA, to avoid introduction of extraneous mutations. The ura3 mutation was rendered homozygous by a second round of transformation resulting in a Ura- strain otherwise isogenic with the parental clinical isolate. Subsequent mutation of the Ura- strain was achieved by targeted mutagenesis using the URA3 gene as a selectable marker. URA3 selection was used repeatedly for the sequential introduction of mutations by flanking the URA3 gene with direct repeats of the Salmonella typhimurium hisG gene. Spontaneous intrachromosomal recombination between the flanking repeats excised the URA3 gene restoring a Ura- phenotype. These Ura- segregants were selected on 5-fluoroorotic acid-containing medium and used in the next round of mutagenesis. To permit the physical mapping of disrupted genes, the 18-bp recognition sequence of the endonuclease I-SceI was incorporated into the hisG repeats. Site-specific cleavage of the chromosome with I-SceI revealed the position of the integrated sequences. PMID- 8349106 TI - Chromosome rearrangements recovered following transformation of Neurospora crassa. AB - New chromosome rearrangements were found in 10% or more of mitotically stable transformants. This was shown for transformations involving a variety of different markers, vectors and recipient strains. Breakpoints were randomly distributed among the seven linkage groups. Controls using untransformed protoplasts of the same strains contained almost no rearrangements. A study of molecularly characterized Am+ transformants showed that rearrangements are frequent when multiple ectopic integration events have occurred. In contrast, rearrangements are absent or infrequent when only the resident locus is restored to am+ by a homologous event. Sequences of the transforming vector were genetically linked to breakpoints in 6 of 10 translocations that were examined using Southern hybridization or colony blots. PMID- 8349107 TI - Two types of sites required for meiotic chromosome pairing in Caenorhabditis elegans. AB - Previous studies have shown that isolated portions of Caenorhabditis elegans chromosomes are not equally capable of meiotic exchange. These results led to the proposal that a homolog recognition region (HRR), defined as the region containing those sequences enabling homologous chromosomes to pair and recombine, is localized near one end of each chromosome. Using translocations and duplications we have localized the chromosome I HRR to the right end. Whereas the other half of chromosome I did not confer any ability for homologs to pair and recombine, deficiencies in this region dominantly suppressed recombination to the middle of the chromosome. These deletions may have disrupted pairing mechanisms that are secondary to and require an HRR. Thus, the processes of pairing and recombination appear to utilize at least two chromosomal elements, the HRR and other pairing sites. For example, terminal sequences from other chromosomes increase the ability of free duplications to recombine with their normal homologs, suggesting that telomere-associated sequences, homologous or nonhomologous, play a role in facilitating meiotic exchange. Recombination can also initiate at internal sites separated from the HRR by chromosome rearrangement, such as deletions of the unc-54 region of chromosome I. When crossing over was suppressed in a region of chromosome I, compensatory increases were observed in other regions. Thus, the presence of the HRR enabled recombination to occur but did not determine the distribution of the crossover events. It seems most likely that there are multiple initiation sites for recombination once homolog recognition has been achieved. PMID- 8349109 TI - Molecular characterization and rescue of acatalasemic mutants of Drosophila melanogaster. AB - The enzyme catalase protects aerobic organisms from oxygen-free radical damage by converting hydrogen peroxide to molecular oxygen and water before it can decompose to form the highly reactive hydroxyl radical. Hydroxyl radicals are the most deleterious of the activated oxygen intermediates found in aerobic organisms. If formed, they can react with biological molecules in their proximity; the ensuing damage has been implicated in the increasing risk of disease and death associated with aging. To study further the regulation and role of catalase we have undertaken a molecular characterization of the Drosophila catalase gene and two potentially acatalasemic alleles. We have demonstrated that a previously existing allele, Catn4, likely contains a null mutation, a mutation which blocks normal translation of the encoded mRNA. The Catn1 mutation appears to cause a significant change in the protein sequence; however, it is unclear why this change leads to a nonfunctioning protein. Viability of these acatalasemic flies can be restored by transformation with the wild-type catalase gene; hence, we conclude that the lethality of these genotypes is due solely to the lack of catalase. The availability of flies with transformed catalase genes has allowed us to address the effect of catalase levels on aging in Drosophila. Though lack of catalase activity caused decreased viability and life span, increasing catalase activity above wild-type levels had no effect on normal life span. PMID- 8349108 TI - Genetic and molecular characterization of the Caenorhabditis elegans spermatogenesis-defective gene spe-17. AB - Two self-sterile mutations that define the spermatogenesis-defective gene spe-17 have been analyzed. These mutations affect unc-22 and fail to complement each other for both Unc-22 and spermatogenesis defects. Both of these mutations are deficiencies (hcDf1 and hDf13) that affect more than one transcription unit. Genomic DNA adjacent to and including the region deleted by the smaller deficiency (hcDf1) has been sequenced and four mRNAs (including unc-22) have been localized to this sequenced region. The three non unc-22 mRNAs are shown to be sex-specific: a 1.2-kb mRNA that can be detected in sperm-free hermaphrodites and 1.2- and 0.56-kb mRNAs found in males. hDf13 deletes at least 55 kb of chromosome IV, including all of unc-22, both male-specific mRNAs and at least part of the female-specific mRNA. hcDf1, which is approximately 15.6 kb, deletes only the 5' end of unc-22 and the gene that encodes the 0.56-kb male-specific mRNA. The common defect that apparently accounts for the defective sperm in hcDf1 and hDf13 homozygotes is deletion of the spe-17 gene, which encodes the 0.56-kb mRNA. Strains carrying two copies of either deletion are self-fertile when they are transgenic for any of four extrachromosomal array that include spe-17. We have sequenced two spe-17 cDNAs, and the deduced 142 amino acid protein sequence is highly charged and rich in serine and threonine, but shows no significant homology to any previously determined protein sequence. PMID- 8349110 TI - Molecular variation of Adh and P6 genes in an African population of Drosophila melanogaster and its relation to chromosomal inversions. AB - Four-cutter molecular polymorphism of Adh and P6, and chromosome inversion polymorphism of chromosome II were investigated in 95 isogenic lines of an Ivory Coast population of Drosophila melanogaster, a species assumed to have recently spread throughout the world from a West African origin. The P6 gene showed little linkage disequilibrium with the In(2L)t inversion, although it is located within this inversion. This suggests that the inversion and the P6 locus have extensively exchanged genetic information through either double crossover or gene conversion. Allozymic variation in ADH was in linkage disequilibrium with In(2L)t and In(2R)NS inversions. Evidence suggests either that inversion linkage with the Fast allele is selectively maintained, or that this allele only recently appeared. Molecular polymorphism at the Adh locus in the Ivory Coast is not higher than in North American populations. New haplotypes specific to the African population were found, some of them connect the "WaS-like" haplotypes found at high frequencies in the United States to the other slow haplotypes. Their relation with In(2L)t supports the hypothesis that WaS recently recombined away from an In(2L)t chromosome which may be the cause of its divergence from the other haplotypes. PMID- 8349111 TI - The Drosophila sex determination gene snf is utilized for the establishment of the female-specific splicing pattern of Sex-lethal. AB - The Drosophila snf gene is a positive regulator of the sex determination gene Sex lethal in both the germline and the soma. Its role in the soma is only evident when the probability of Sex-lethal activation has been reduced. For instance, in an otherwise wild-type background, females homozygous for a weak snf mutation produce both male and female progeny; however, when mated to males hemizygous for a null allele of Sex-lethal, they produce only male progeny. We demonstrate that the lack of female progeny is due to aberrant Sex-lethal regulation in late embryogenesis. In these mutant embryos, there is little accumulation of the late female-specific spliced RNAs and proteins. In contrast, in early embryogenesis, Sex-lethal regulation is not affected. The accumulation of both the early Sex lethal transcripts and proteins is normal. These results suggest that the wild type product of snf plays an important role in establishing the female-specific RNA splicing pattern of Sex-lethal. Whether snf influences the female-specific splice site choice directly or indirectly remains to be determined. PMID- 8349113 TI - The genetic analysis of achiasmate segregation in Drosophila melanogaster. III. The wild-type product of the Axs gene is required for the meiotic segregation of achiasmate homologs. AB - The regular segregation of achiasmate chromosomes in Drosophila melanogaster females is ensured by two distinct segregational systems. The segregation of achiasmate homologs is assured by the maintenance of heterochromatic pairing; while the segregation of heterologous chromosomes is ensured by a separate mechanism that may not require physical association. AxsD (Aberrant X segregation) is a dominant mutation that specifically impairs the segregation of achiasmate homologs; heterologous achiasmate segregations are not affected. As a result, achiasmate homologs frequently participate in heterologous segregations at meiosis I. We report the isolation of two intragenic revertants of the AxsD mutation (Axsr2 and Axsr3) that exhibit a recessive meiotic phenotype identical to that observed in AxsD/AxsD females. A third revertant (Axsr1) exhibits no meiotic phenotype as a homozygote, but a meiotic defect is observed in Axsr1/Axsr2 females. Therefore mutations at the AxsD locus define a gene necessary and specific for homologous achiasmate segregation during meiosis. We also characterize the interactions of mutations at the Axs locus with two other meiotic mutations (ald and ncd). Finally, we propose a model in which Axs+ is required for the normal separation of paired achiasmate homologs. In the absence of Axs+ function, the homologs are often unable to separate from each other and behave as a single segregational unit that is free to segregate from heterologous chromosomes. PMID- 8349112 TI - The 3' regulatory region of the Abdominal-B gene: genetic analysis supports a model of reiterated and interchangeable regulatory elements. AB - The Abdominal-B (Abd-B) gene is one of three genes in the bithorax complex, a cluster of homeotic genes in Drosophila. During embryogenesis Abd-B is expressed in a complex pattern, producing four different transcript classes, each of which exhibits a unique spatial pattern of expression. Proper regulation of the class A transcripts is required for appropriate development of the fifth through eighth abdominal segments and is mediated, in part, by a 60-kb regulatory region located 3' of the gene. We have isolated a new mutation, designated Abd-BCorset, which is caused by a deletion that leaves 15 kb of the 3' regulatory sequences immediately adjacent to the gene, but removes 45 kb of the more distant 3' regulatory elements. This mutation produces an unexpected homeotic segmental transformation of the fourth through seventh abdominal segments, and has been analyzed by genetic and molecular techniques. In situ hybridization to Abd-BCorset embryos shows a uniform and moderate level of the Abd-B class A transcript in the posterior abdomen, rather than the normal graded pattern of expression. Our analysis of the Abd-BCorset mutation has prompted a model of the 3' regulatory region of Abd-B based on reiterated cell type-specific elements controlled by adjacent position-sensitive activating elements. The gradient of Abd-B expression normally observed in the posterior abdomen appears to be achieved by varying the number of reiterated elements that are active in each segment. PMID- 8349115 TI - Codon usage bias and base composition of nuclear genes in Drosophila. AB - The nuclear genes of Drosophila evolve at various rates. This variation seems to correlate with codon-usage bias. In order to elucidate the determining factors of the various evolutionary rates and codon-usage bias in the Drosophila nuclear genome, we compared patterns of codon-usage bias with base compositions of exons and introns. Our results clearly show the existence of selective constraints at the translational level for synonymous (silent) sites and, on the other hand, the neutrality or near neutrality of long stretches of nucleotide sequence within noncoding regions. These features were found for comparisons among nuclear genes in a particular species (Drosophila melanogaster, Drosophila pseudoobscura and Drosophila virilis) as well as in a particular gene (alcohol dehydrogenase) among different species in the genus Drosophila. The patterns of evolution of synonymous sites in Drosophila are more similar to those in the prokaryotes than they are to those in mammals. If a difference in the level of expression of each gene is a main reason for the difference in the degree of selective constraint, the evolution of synonymous sites of Drosophila genes would be sensitive to the level of expression among genes and would change as the level of expression becomes altered in different species. Our analysis verifies these predictions and also identifies additional selective constraints at the translational level in Drosophila. PMID- 8349116 TI - Detecting marker-QTL linkage and estimating QTL gene effect and map location using a saturated genetic map. AB - A simulation study was carried out on a backcross population in order to determine the effect of marker spacing, gene effect and population size on the power of marker-quantitative trait loci (QTL) linkage experiments and on the standard error of maximum likelihood estimates (MLE) of QTL gene effect and map location. Power of detecting a QTL was virtually the same for a marker spacing of 10 cM as for an infinite number of markers and was only slightly decreased for marker spacing of 20 or even 50 cM. The advantage of using interval mapping as compared to single-marker analysis was slight. "Resolving power" of a marker-QTL linkage experiment was defined as the 95% confidence interval for the QTL map location that would be obtained when scoring an infinite number of markers. It was found that reducing marker spacing below the resolving power did not add appreciably to narrowing the confidence interval. Thus, the 95% confidence interval with infinite markers sets the useful marker spacing for estimating QTL map location for a given population size and estimated gene effect. PMID- 8349114 TI - Compositional heterogeneity and patterns of molecular evolution in the Drosophila genome. AB - The rates and patterns of molecular evolution in many eukaryotic organisms have been shown to be influenced by the compartmentalization of their genomes into fractions of distinct base composition and mutational properties. We have examined the Drosophila genome to explore relationships between the nucleotide content of large chromosomal segments and the base composition and rate of evolution of genes within those segments. Direct determination of the G + C contents of yeast artificial chromosome clones containing inserts of Drosophila melanogaster DNA ranging from 140-340 kb revealed significant heterogeneity in base composition. The G + C content of the large segments studied ranged from 36.9% G + C for a clone containing the hunchback locus in polytene region 85, to 50.9% G + C for a clone that includes the rosy region in polytene region 87. Unlike other organisms, however, there was no significant correlation between the base composition of large chromosomal regions and the base composition at fourfold degenerate nucleotide sites of genes encompassed within those regions. Despite the situation seen in mammals, there was also no significant association between base composition and rate of nucleotide substitution. These results suggest that nucleotide sequence evolution in Drosophila differs from that of many vertebrates and does not reflect distinct mutational biases, as a function of base composition, in different genomic regions. Significant negative correlations between codon-usage bias and rates of synonymous site divergence, however, provide strong support for an argument that selection among alternative codons may be a major contributor to variability in evolutionary rates within Drosophila genomes. PMID- 8349117 TI - A class of population genetic questions formulated as the generalized occupancy problem. AB - In categorical genetic data analysis when the sampling units are classified into an arbitrary number of distinct classes, sometimes the sample size may not be large enough to apply large sample approximations for hypothesis testing purposes. Exact sampling distributions of several statistics are derived here, using combinatorial approaches parallel to the classical occupancy problem to help overcome this difficulty. Since the multinomial probabilities can be unequal, this situation is described as a generalized occupancy problem. The sampling properties derived are used to examine nonrandomness of occurrence of mutagen-induced mutations across loci, to devise tests of Hardy-Weinberg proportions of genotype frequencies in the presence of a large number of alleles, and to provide a global test of gametic phase disequilibrium of several restriction site polymorphisms. PMID- 8349118 TI - Empirical tests of some predictions from coalescent theory with applications to intraspecific phylogeny reconstruction. AB - Empirical data sets of intraspecific restriction site polymorphism in Drosophila have been gathered in order to test hypotheses derived from coalescent theory. Three main ideas are tested: (1) haplotype frequency in the sample contains information on the topological position of a given haplotype in a cladogram, (2) the frequency of a haplotype is related to the number of mutational connections to other haplotypes in the cladogram and (3) geographic location can be used to infer topological positioning of haplotypes in a cladogram. These relationships can then be used to better estimate intraspecific phylogenies in two ways: (1) rooting the phylogeny and (2) resolving ambiguities in a cladogram. This information will allow one to reduce the number of alternative phylogenies and incorporate the uncertainties involved in reconstructing intraspecific phylogenies into subsequent analyses that depend heavily on the topology of the tree. PMID- 8349119 TI - Substitution processes in molecular evolution. I. Uniform and clustered substitutions in a haploid model. AB - A computer simulation of the process of nucleotide substitutions in a finite haploid population subject to selection in a randomly fluctuating environment provides a number of unexpected results. For rapidly fluctuating environments, substitutions are more regular than random. A small mutation-rate approximation is used to explain the regularity. The explanation does not depend heavily on the particulars of the haploid model, leading to the conjecture that many symmetrical models of molecular evolution with rapidly changing parameters may exhibit substitutions that are more regular than random. When fitnesses change very slowly, the simulation shows that substitutions are more clumped than random. Here a small-mutation approximation shows that the clustering is due to the increase in fitness that accompanies each successive substitution with a consequent lowering of the effective mutation rate. The two observations taken together suggest that the common observation that amino acid substitutions are clustered in time is due to the presence of parameters that change very slowly. PMID- 8349121 TI - The effect of selection on the phenotypic variance. AB - We consider the within-generation changes of phenotypic variance caused by selection w(x) which acts on a quantitative trait x. If before selection the trait has Gaussian distribution, its variance decreases if the second derivative of the logarithm of w(x) is negative for all x, while if it is positive for all x, the variance increases. PMID- 8349120 TI - VNTR allele frequency distributions under the stepwise mutation model: a computer simulation approach. AB - Variable numbers of tandem repeats (VNTRs) are a class of highly informative and widely dispersed genetic markers. Despite their wide application in biological science, little is known about their mutational mechanisms or population dynamics. The objective of this work was to investigate four summary measures of VNTR allele frequency distributions: number of alleles, number of modes, range in allele size and heterozygosity, using computer simulations of the one-step stepwise mutation model (SMM). We estimated these measures and their probability distributions for a wide range of mutation rates and compared the simulation results with predictions from analytical formulations of the one-step SMM. The average heterozygosity from the simulations agreed with the analytical expectation under the SMM. The average number of alleles, however, was larger in the simulations than the analytical expectation of the SMM. We then compared our simulation expectations with actual data reported in the literature. We used the sample size and observed heterozygosity to determine the expected value, 5th and 95th percentiles for the other three summary measures, allelic size range, number of modes and number of alleles. The loci analyzed were classified into three groups based on the size of the repeat unit: microsatellites (1-2 base pair (bp) repeat unit), short tandem repeats [(STR) 3-5 bp repeat unit], and minisatellites (15-70 bp repeat unit). In general, STR loci were most similar to the simulation results under the SMM for the three summary measures (number of alleles, number of modes and range in allele size), followed by the microsatellite loci and then by the minisatellite loci, which showed deviations in the direction of the infinite allele model (IAM). Based on these differences, we hypothesize that these three classes of loci are subject to different mutational forces. PMID- 8349122 TI - Variability among members of the Hor-2 multigene family. AB - The hordeins comprise the major prolamin storage proteins of barley. Two major and one minor gene families encode these alcohol-soluble proteins. The Hor-2 gene family encoding the B-hordeins has been estimated to contain 15-30 copies. Although several genes encoding B-hordeins have been cloned and sequenced, little is known about the mechanisms responsible for the generation of the enormous genetic variability at this locus. Polymerase chain reaction sequence amplification provided a simple technique that permitted the amplification of the Hor-2 gene family members from the genomes of several barley genotypes. Sequence analysis of clones permitted the identification of a region within the Hor-2 structural gene that appears to undergo recombinational and slippage-like gene conversion events. In this report we describe variability of the B-hordein genes, possible mechanisms responsible for it, and implications this may have on the evolution of prolamin-encoding gene families. PMID- 8349123 TI - An AT-rich satellite DNA sequence, E180, in alfalfa (Medicago sativa). AB - A DNA fragment of approximately 750 bp was cloned from EcoRI-digested nuclear DNA of alfalfa (Medicago sativa). Southern blot and sequence analysis showed that the cloned DNA fragment represents a tetramer of a highly tandemly repeated DNA sequence of 185-188 bp (E180). The consensus sequence deduced from the four repeating units is 189 bp in length with an AT content of 67%. The copy number of the satellite DNA was estimated to be approximately 1.8 x 10(5) per genome and constitutes about 1% of the alfalfa genome. Sequence comparison revealed no identity to any repetitive DNA sequences that have been published to date. Digestion with HpaII and MspI indicated a high degree of methylation at the internal C of the restriction site CCGG within E180. PMID- 8349124 TI - Within-family selection at an otherwise unselected locus in dairy cattle. AB - Identification of allelic variants with economic importance is feasible via molecular genetic techniques. This information can be used to increase the frequency of favourable alleles in dairy cattle. The effect of selection on the genotype within families in the early stages of life is examined. Three different strategies are considered: (1) random mating of bull sires with bull dams and with cows, with embryo selection of young bulls and all cows; (2) random mating of bull sires with bull dams, with embryo selection of young bulls only; (3) minimizing or avoiding matings between homozygotes for the unfavourable allele, with embryo selection of young bulls. Selection strategies assume the use of reproductive technologies such as embryo transfer to produce large family sizes for within-family selection to be practiced. All the three strategies increase the frequency of the favourable allele rapidly. Strategy 1 gives the fastest increase in the frequency of the favourable allele. The increase in the frequency of the favourable allele is slower under random mating (strategy 2) than under a negative assortative mating (strategy 3). This is a novel example of increased selection response with negative assortative mating. PMID- 8349125 TI - Conservative genome size and rapid chromosomal evolution in the South American tuco-tucos (Rodentia: Ctenomyidae). AB - Genome size (the amount of DNA per cell) was measured by flow-cytometric analysis in seven species of a chromosomally variable rodent genus: Ctenomys boliviensis, C. conoveri, C. frater, C. leucodon, C. lewisi, C. opimus, and C. steinbachi. The mean genome size of these species was 7.19 pg DNA and little inter- and intra specific variation was observed. Genome size was not correlated with diploid number, suggesting that chromosomal evolution at this level is independent of total DNA content. A hypothetical taxonomic unit optimization procedure was carried out using genome size change on a Wagner tree derived from allozyme data. Allozyme evolution and genome size change are linked by a weak, but significant, negative correlation suggestive of preferential genic evolution in the absence of genome size evolution. PMID- 8349126 TI - Genetic maps of the sheep blowfly Lucilia cuprina: linkage-group correlations with other dipteran genera. AB - Linkage data and revised genetic maps for 72 autosomal loci in Lucilia cuprina are presented. Comparison of the linkage relationships of biochemically and morphologically similar mutations in Ceratitis capitata, Drosophila melanogaster, and Musca domestica supports the hypothesis that the major linkage elements have survived relatively intact during evolution of the higher Diptera. The relationship of the linkage groups of the mosquito Aedes aegypti to these species is less clear. PMID- 8349127 TI - Chromosomal rearrangements in rock wallabies, Petrogale (Marsupialia: Macropodidae). VIII. An investigation of the nonrandom nature of karyotypic change. AB - Although the nonrandom nature of many chromosome breaks is well known, few studies have investigated the potential significance of this breakage specificity in chromosome evolution. The macropod genus Petrogale is an ideal group in which to investigate this phenomenon, since it comprises a large number of chromosomal forms, many of which appear to have differentiated relatively recently. By exposing Petrogale cells to mutagenic agents it should be possible to compare the distribution and abundance of induced breaks with those that are known to have occurred in vivo during the chromosomal differentiation of the genus. In this study, breaks were induced in mitotic chromosomes from P. assimilis and P. mareeba by exposing synchronized cultured fibroblasts to low doses of gamma radiation. The results were remarkably similar for both species and the distribution of breaks among the chromosomes appeared to be nonrandom. It was found that chromosomes 5, 6, and (possibly) 10 had a substantially higher rate of breakage than expected. These are also the chromosomes that occur disproportionately among the rearrangements identified in Petrogale. While the distribution of breaks along the chromosome appeared uniform or normal for most chromosomes, a putative "hot spot" was identified near the centromere in chromosome 5 of P. mareeba and in a homologous position near the telomere of chromosome 5 in P. assimilis. In a further experiment, a 1- to 2-h pulse of mitomycin C was used to induce centric fusions in cultured fibroblasts of P. penicillata (2n = 22); 2408 cells were examined and 112 fusions were identified. While it was found that all chromosomes participated in forming fusions, chromosome 10 was found to be most frequently involved, being present in 28.6% of the identified fusions. This frequency is far greater than would be expected if fusions were to occur at random (10%). It is significant then that chromosome 10 has been involved in five of the eight centric fusions that have been identified in Petrogale and that it is also the chromosome that has been most frequently rearranged in Petrogale. These results suggest that features of the karyotype may influence the distribution and frequency of chromosome breaks and therefore the rate and nature of chromosome evolution. PMID- 8349128 TI - Random amplified polymorphic DNA markers for DNA fingerprinting and genetic variability assessment of minute parasitic wasp species (Hymenoptera: Mymaridae and Trichogrammatidae) used in biological control programs of phytophagous insects. AB - Biological control of insects that feed on our crops has become more practical in recent years by mass release of egg parasitoid microhymenoptera. Trichogramma species are now commercially reared and spread in commercial fields to control specific insect pests. Microhymenoptera species are, however, very small and morphologically indistinguishable within species, although strains of a given species differ in their efficiency to control specific insect pests. Traditional taxonomy is unable to differentiate microhymenoptera species at the strain level. It is becoming increasingly important to develop a reliable system to monitor genetic variations both within and between strains of commercially important microhymenoptera, to detect genetic drift occurring during several generations of multiplication, to protect patents, and to certify the lots of commercially released microhymenoptera. We have developed a system based on DNA markers to rapidly characterize individuals of five species of microhymenoptera from the genus Anaphes and Trichogramma including a new species of Anaphes not previously described. The main components of our system are a rapid and simple DNA micro extraction method and fast DNA polymorphism analyses based on random amplified polymorphic DNA markers. PMID- 8349129 TI - Molecular characterization of a mouse Y chromosomal repetitive sequence amplified in distantly related species in the genus Mus. AB - This report describes a 1.1 kb long mouse Y chromosomal sequence designated 142 4. It has a 42% GC content and is rich in short direct and inverted repeats. 142 4 related sequences are repeated about 200 times in the Mus musculus Y chromosome and their distribution was visualized by in situ hybridization. 142-4 detected a restriction fragment length polymorphism that differentiated between the M. m. musculus type and the M. m. domesticus type Y chromosome. Southern blot analysis of DNAs isolated from a panel of mouse species showed that 142-4 related sequences were amplified in the Y chromosomes of M. minutoides, M. musculus, M. saxicola, M. spicilegus, and M. spretus but not in those of M. caroli, M. cookii, and M. pahari. These results suggest that 142-4 related sequences are evolutionarily unstable and their accumulation patterns do not correlate with the known phylogenetic relationships of mouse species in the genus Mus. PMID- 8349130 TI - Potential of trispecies bridge crosses and random amplified polymorphic DNA markers for introgression of Medicago daghestanica and M. pironae germplasm into alfalfa (M. sativa). AB - This report describes the production and cytology of the first interspecific hybrids between cultivated alfalfa (Medicago sativa L.) at the diploid level (2n = x = 16) and the diploid (2n = 2x = 16) perennial species M. daghestanica and M. pironae. An ovule-embryo culture technique was required to rescue hybrid embryos and all hybrids were diploid. Predominately bivalent chromosome pairing was observed at meiotic metaphase. All F1 hybrids were male and female sterile and no species backcross progeny could be produced. We discovered that trispecies hybrids could be efficiently recovered via crossing diploid F1 interspecific hybrids of M. sativa x M. rupestris with either M. daghestanica or M. pironae. Ovule-embryo culture was also required to recover these trispecies hybrids with recovery efficiency of trispecies hybrids about 10 times greater than for bispecies hybrids. Most chromosomes paired as bivalents in the trispecies hybrids. Importantly, progeny can be recovered from crossing the trispecies hybrids with M. sativa. Therefore, the M. sativa x M. rupestris hybrids provide a bridge cross to potential introgression of M. daghestanica or M. pironae germplasm. Analysis of randomly amplified polymorphic DNA (RAPD) markers in the trispecies hybrids indicates that RAPD markers offer considerable potential for assaying germplasm introgression following complex hybridization of the type reported here. PMID- 8349131 TI - Application of the random amplified polymorphic DNA technique for the detection of polymorphism among wild and cultivated tetraploid wheats. AB - Development of a high-density genetic linkage map of cultivated wheats using conventional molecular markers has lagged behind the other major food crops such as rice and tomato because of the large genome size and limited levels of genetic polymorphisms. Recently, random amplified polymorphic DNAs (RAPDs) have been suggested to provide an alternative to visualize more polymorphism. For the construction of a genetic linkage map in tetraploid wheats, one can use a strategy of intersubspecific crosses between the most dissimilar wild and cultivated tetraploid wheats that are easy to hybridize and result in fertile progeny. An assessment of the level of RAPDs among different accessions and varieties of wild and cultivated tetraploid wheats is required to fulfill this objective. We present here the data obtained using RAPD analysis of 40 primers in 20 accessions of wild tetraploid emmer wheats (Triticum turgidum L. ssp. dicoccoides) and 10 genotypes of cultivated tetraploid durum wheats (Triticum turgidum L. ssp. durum) selected from geographically diverse locations. We have observed a higher level of polymorphism among different accessions of wild emmer wheat from Israel. Turkey, and Jordan than the group of cultivated American, Turkish, and Syrian durum wheats. These data have been used to generate a dendrogram suggesting the genetic relationships among these genotypes, and the most dissimilar genotypes are identified for future mapping and gene tagging work. PMID- 8349132 TI - [Acute myocardial infarct and pregnancy. Report of a case and review of the literature]. AB - We present the case of a 39 year old woman with 36 weeks pregnancy and acute myocardial infarction seen at the Hospital ABC. Acute myocardial infarction during pregnancy is not very common and it's incidence has been calculated in 1:10,000 pregnancies it takes place more often during the third trimester, so we have to keep it in mind for early diagnosis. Mortality increases when it occurs during the third trimester close to delivery, during labor or in the first 7 days post delivery. Initial management of this high risk patients has to be done in a intensive care unit and requires of the intervention of multiple specialists, to decrease maternal and fetal mortality. PMID- 8349133 TI - [McIndoe operation in a case of vaginal agenesis. Considerations on the subject]. AB - Congenital absence of the vagina depends on partial or complete failure of Mullerian duct development. The ovaries develop normally and the fimbrial ends of the tubes are vestigial but there is no uterus, cervix or vagina. The urinary and genital systems and some skeletal portions developing from Mullerian ducts are so closely linked embryologically that congenital abnormality of kidney and bones is said to accompany genital defects in approximately 20% of cases. Several surgical techniques have been proposed but the gynecologist can have sufficient experience to choose the most suitable treatment according to the pecularities of each case. McIndoe Operation offers the best possible result opening a space between the ureta and the rectum and placing within in a large penile shaped mold draped with a split skin graft. This operation can result in a vagina that looks and feels absolutely normal but the most discouraging however is the time required for the completion of the whole treatment. There are several photos illustrating the procedure. PMID- 8349135 TI - [Conservative therapy of ectopic pregnancy with methotrexate]. AB - Ectopic pregnancy (EP) treated by traditional methods, signifies an approximate lose of fertility capacity of the patient, of 50%. The early diagnosis allows conservative treatment with metotrexate (MTXE), with the objective of preserving the affected tube (salpynx) and its function. Early detection of EP, intact, was done, in 11 cases, with the following parameters: clinical picture, ultrasonography (Us) (empty uterus, adnexial mass and free fluid; adnexial ring or extrauterine embryo); quantitative determination of beta fraction of chorionic gonadotropin (CGH b) and laparoscopic observation, when the following characteristics were met: tubal pregnancy, no greater than 30 mm, intact tubarian serosa, lack of active bleeding and visualization of all pelvic cavity. MTXE 12.5 mg, intrasacularly via laparoscopy in eight patients, and three by laparotomy. The ulterior control of the procedure was: careful surveillance during eight days, Us daily and CGH b in two occasions; ten patients evolutionated satisfactorily, two of them required additional dosis of MTXE, parenterally, 0.5 mg/kg and citovorum factor, 0.1 mg/kg/4 days. The obtained conclusions are: 1. Conservative treatment with MTXE may be carried out provided the conditions established before, are met. 2. The patient's follow up must be precise and because of the high cost of the determination every third day of CGH b, Us may be used. Hysterosalpingography was done in five patients after six months of the procedure, and tubal permeability was seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349134 TI - [Ovulation induction with human menopausal gonadotropins in hypothalamic hypophyseal disfunction]. AB - This is a report on the institutional experience of the use of Human Menopausal Gonadotropins (HMG) in anovulatory women diagnosed as hypothalamic-hypophysiary dysfunction of Group II of WHO with previous failure to chlomifen citrate therapy. In a period of three years 180 patients were gathered with 420 cycle of treatment, obtaining ovulation in 340 cycles (81%). The ovarian hyperstimulation syndrome (OHS) was present in 15 cases (3.5%). There were 115 pregnancies that correspond to 33.8% of oculatory cycles and to 63.8% of the amount of patients. Multiple pregnancy incidence was 10.4%, and the gestational loses rate was 26%; these results are similar to what has been reported in literature. It is concluded that this medication is a good option of treatment for this type of patients, provided that there are the necessary means to expert and adequate surveillance. PMID- 8349136 TI - [Guillain-Barre syndrome and pregnancy]. AB - Guillain-Barre syndrome is a rare occurrence in pregnant women. We describe the case of a 21-year old woman, seen at "Nuevo Hospital Civil de Guadalajara" with a term pregnancy, who presented with limbs weakness and paresthesias, drowsiness and malaise. Her vital signs were normal but she was quadriparetic, there was muscular atrophy in the extremities and deep tendon reflexes were decreased. Spinal fluid analysis revealed a protein of 71.2 mg/dl, glucosa 48 mg/dl and no white cells and both Gram stain and routine cultures were negative. EMG studies reported poliradiculoneuritis; a C-section was done, and both the mother and a newborn girl did very well. Guillain-Barre syndrome should be suspected in similar cases in order to offer prompt intervention. PMID- 8349137 TI - Protection by vitamin E, selenium, and beta-carotene against oxidative damage in rat liver slices and homogenate. AB - Male Sprague-Dawley (SD) rats were fed a vitamin E and selenium deficient diet and diets supplemented with vitamin E, selenium, beta-carotene, and a combination of the three. Tissue slices and homogenate of liver were incubated at 37 degrees C with and without the presence of prooxidants. The effect of vitamin E, selenium, beta-carotene, and the combination of the three antioxidants on the oxidative damage to rat liver tissue was studied by measuring the production of oxidized heme proteins in both tissue slices and homogenate during spontaneous and prooxidant-induced oxidation. The diet with the combination of all three antioxidants showed a strong protective effect against oxidative damage to heme proteins in contrast to the antioxidant-deficient diet. In general, diets with vitamin E, selenium, and beta-carotene were less effective than the combination of all three antioxidants. The protective effect of antioxidants on the heme protein oxidation was correlated with their inhibitory effect on lipid peroxidation measured as the production of thiobarbituric acid-reactive substance (TBARS). The protection of antioxidants on heme proteins was also dependent on the type of oxidation inducer. Possible mechanisms of antioxidants against oxidation in liver tissues are discussed. PMID- 8349138 TI - Recognition of oxidized DNA bases by sera of patients with inflammatory diseases. AB - Chronic inflammatory conditions result from or contribute to many diseases. Prominent among them is systemic lupus erythematosus (SLE). Sera of SLE patients contain an array of various auto-antibodies (Ab), including antinuclear Ab of unknown etiologies. The most puzzling is formation of Ab directed against autologous DNA. Our hypothesis was that increased oxidant production causes oxidation of DNA bases, which provide antigenic determinants that elicit antioxidized DNA Ab. To test this hypothesis, we used oxidized DNA nucleoside (5 hydroxymethyl-2'-deoxyuridine [HMdU]) conjugated to bovine serum albumin (HMdU BSA) as the antigen. The results of the enzyme-linked immunosorbent assay showed that these Abs are sensitively detectable in SLE sera and sera of various other inflammatory autoimmune diseases. The titers of anti-HMdU Ab were significantly higher (p < .01) than those present in the control sera. Anti-HMdU Ab were predominantly of the IgM isotype, with low levels of IgG and no IgA. Anti-HMdU Ab bound to the HMdU-BSA-coated wells in a concentration- and time-dependent manner. That binding was inhibited by HMdU-BSA and to a lesser extent by thymidine-BSA, a normal nucleoside conjugate. The specific binding appears to be inversely related to the age of the patients, but no significant differences were observed between the sexes of the same age. PMID- 8349139 TI - Interaction of viable group A streptococci and hydrogen peroxide in killing of vascular endothelial cells. AB - Previous studies have shown that the streptococcal hemolysin, streptolysin S, is capable of interacting with hydrogen peroxide (H2O2) to injure vascular endothelial cells (Free Radic. Biol. Med. 7:369-376; 1989). To extend these observations, intact group A streptococci (strain 203S) were examined for ability to injure endothelial cells alone and for ability to injure the same cells in the presence of sublethal concentrations of H2O2 (generated from glucose/glucose oxidase). While neither control bacteria nor bacteria that had been pretreated with poly-L-histidine to render them cationic were cytotoxic to endothelial cells by themselves under the conditions of the experiment, endothelial cells were injured by combinations of streptococcal cells and sublytic amounts of H2O2. Taken together, these data suggest that the sequelae which often occur following primary infection with group A streptococci may be the result of a combined assault of host inflammatory cells and the invading bacteria on the vascular lining cells of the host. PMID- 8349140 TI - Oxidation of heme proteins as a measure of oxidative damage to liver tissue slices. AB - Oxidative damage to heme proteins in rat liver tissue slices was studied. Tissue slices were incubated in Krebs-Ringer phosphate (KRP) buffer at 37 degrees C with and without the presence of prooxidants. The absorbance spectra (500-640 nm) of heme proteins of tissue slices obtained from both spontaneous and prooxidant induced oxidation were analyzed with a heme protein spectra analysis program (HPSAP) developed in this laboratory. The dominant heme proteins in a fresh nonperfused tissue slice were hemoglobin and reduced cytochromes of mitochondria. In an oxidized tissue slice, the major oxidized product was hemichrome. Bromotrichloromethane, t-butyl hydroperoxide, and ferrous ion accelerated the oxidative reactions, and the amount of oxidized products was dependent on the incubation time as well as the type and concentration of prooxidants. PMID- 8349141 TI - Boomerang effect between [Met]-enkephalin derivatives and human polymorphonuclear leukocytes. AB - [Met]-enkephalin or its precursor, pre-[Met]-enkephalin, were exposed to activated oxygen species produced by human phorbol myristate acetate (PMA) stimulated polymorphonuclear leukocytes (PMNs) and then analyzed by high-pressure liquid chromatography (HPLC). The chromatograms recorded at the tyrosine maximum wavelength (lambda em 300 nm and lambda ex 280 nm) showed the formation of new peptides by oxidation of methionyl residue in position 5 and ortho, meta, or para hydroxylation of phenylalanyl residue in position 4. The chromatograms recorded at the dityrosine maximum wavelength (lambda em 400 nm and lambda ex 325 nm) showed the formation of new dimeric peptides which contained two [Met]-enkephalin derivatives linked by a dityrosyl group. These new peptides were tested for chemiluminescence response to PMA-stimulated PMNs. [Met]-enkephalin, pre-[Met] enkephalin, and the methionyl-oxidized derivatives suppressed the PMA-induced respiratory burst of PMNs. Conversely, after hydroxylation by activated oxygen species released by stimulated PMNs, these peptides enhanced the PMA-induced respiratory burst of PMNs. In the same conditions, dimeric peptides had no effect. PMID- 8349142 TI - Hyperoxic lung injury in Fischer-344 and Sprague-Dawley rats in vivo. AB - Supplemental oxygen remains an important therapy for pulmonary insufficiency, despite the potential adverse effects of hyperoxic exposures. Recently, He et al. reported that hyperoxic ventilation more readily damaged isolated perfused lungs from Fischer-344 rats than from Sprague-Dawley rats (Am. J. Physiol. 259:L451), which correlates with the previously reported strain differences in hepatic responses to diquat-induced oxidant stress in vivo (J. Pharmacol. Exp. Ther. 235:172). We therefore examined the differences in hyperoxic lung injury in Fischer-344 and Sprague-Dawley rats in vivo. Adult male rats were exposed to > 95% O2 and were sacrificed after 24, 48, or 60 h. Control animals were maintained in room air. Dramatically greater increases in pleural effusions and bronchoalveolar lavage protein concentrations in response to hyperoxia were observed in the Fischer-344 rats than in the Sprague-Dawley rats (p < .05 at both 48 and 60 h for both measurements). Additionally, the glutathione concentrations in alveolar lining fluid decreased from 800 microM to 115 microM in Fischer-344 rats after 60 h of > 95% O2, but did not change in Sprague-Dawley rats. We conclude that the greater susceptibility of Fischer-344 than of Sprague-Dawley rats to hyperoxic lung injury in vitro reported previously also is observed in vivo and that this strain difference offers unique opportunities to study mechanisms of hyperoxic lung injury. PMID- 8349143 TI - Toxicity, single-strand breaks, and 5-hydroxymethyl-2'-deoxyuridine formation in human breast epithelial cells treated with hydrogen peroxide. AB - DNA damage induced by oxidants includes formation of DNA strand breaks as well as oxidative damage to DNA bases. We quantified both forms of DNA damage concurrently in two model human breast epithelial cell lines treated with hydrogen peroxide to compare the dose-dependent induction of each form of DNA damage with growth inhibition. Antioxidant defenses also were quantified. MCF-7 breast cancer cells had relatively higher levels of non-protein thiols, oxidized glutathione (GSSG) reductase, catalase, and superoxide dismutase than did the MCF 10A line of immortalized, but not transformed, human breast epithelial cells. The levels of antioxidant defenses were not predictive of endogenous oxidative DNA damage levels nor of toxicity and DNA damage induced by hydrogen peroxide. The endogenous levels of 5-hydroxymethyl-2'-deoxyuridine were higher in MCF-7 than MCF-10A cells. The cells were treated with 10-200 microM hydrogen peroxide for 15 min at 37 degrees C in complete media. Low concentrations of hydrogen peroxide were growth stimulatory to both cell lines. At higher concentrations, growth inhibition by hydrogen peroxide was greater in MCF-7 than in MCF-10A cells. Accordingly, induction of both single-strand DNA breaks and 5-hydroxymethyl-2' deoxyuridine in DNA was greater in MCF-7 than MCF-10A cells. In both cell lines, the dose-dependent induction of single-strand breaks paralleled growth inhibition more closely than did formation of 5-hydroxymethyl-2'-deoxyuridine. PMID- 8349144 TI - Glutathione system of human retina: enzymatic conjugation of lipid peroxidation products. AB - The major aspects of the glutathione (GSH)-related antioxidant defense of human retina are presented. These include concentration of GSH and activities of some GSH-dependent enzymes: glutathione peroxidase, glutathione disulfide reductase, and glutathione S-transferase toward a broad spectrum substrate 1-chlor-2,4 dinitrobenzene and a toxic product of lipid peroxidation (4-hydroxynonenal). The presence of a relatively high GSH concentration, GSH peroxidase activity, and GSH S-transferase specific activity toward 4-hydroxynonenal in human retina might constitute a central defense mechanism in inflammation-promoted oxidative stress and subsequent lipid peroxidation. The use of different substrates for the determination of the GSH peroxidase activity showed no statistically significant difference, thus suggesting the lack of Se-independent GSH peroxidase in human retina. Large individual variations were obtained for GSH concentration and the different activities tested; the apparent correlation with age of these findings is currently under investigation. PMID- 8349145 TI - Richard O. Recknagel. PMID- 8349147 TI - Trevor F. Slater. PMID- 8349146 TI - 32P-postlabeling assay for free radical-induced DNA damage: the formamido remnant of thymine. AB - A prominent lesion in DNA exposed to oxidative free radicals results from the degradation of thymine leaving a formamido remnant. A 32P-postlabeling assay has been developed for the detection of the formamido lesion. The assay is based on the circumstance that the lesion prevents hydrolysis by nuclease P1 of the phosphoester bond 3' to the damaged nucleoside. Thus, a nuclease P1 plus acid phosphatase digest of DNA generates mostly nucleosides whereas the formamido lesion is rendered as a modified dinucleoside monophosphate. Dinucleoside monophosphates, but not nucleosides, are apt substrates for 32P-postlabeling by polynucleotide kinase. The assay was applied to calf thymus DNA X-irradiated in oxygenated solution. The formamido lesion could be detected down to a dose of a few Gy. PMID- 8349148 TI - Interaction between allopurinol and copper: possible role in myocardial protection. AB - Allopurinol, a potent inhibitor of xanthine oxidase, is known to effectively protect the heart against damage in patients undergoing cardiac bypass surgery. There is still an ambiguity concerning the presence of xanthine oxidase in the human heart. Thus, the mechanism underlying the protective effect of allopurinol is unclear. Transition metal ions, such as iron and copper, can participate in single-electron reactions and mediate the formation of oxygen-derived free radicals. In this study the interaction between allopurinol and Cu(II) was investigated. Spectrophotometric investigation shows that allopurinol (0-0.8 mM) form a 1:1 complex with Cu(II) ions (0-0.8 mM) with a specific absorbance peak at 364 nm. Also, the rate constant (k) for the copper-catalyzed aerobic oxidation of ascorbate was markedly decreased in the presence of allopurinol (from 0.068 min-1 to 0.014 min-1). Allopurinol substantially reduced the copper-mediated and ascorbate-driven DNA breakage. Spectrophotometric measurements did not indicate a specific interaction between iron ions and allopurinol. It is suggested that the beneficial effects of allopurinol during reperfusion of the heart could stem from its chelation of copper, yielding a complex with low redox activity. PMID- 8349149 TI - Color Doppler sonography of ovarian masses: the importance of a multiparameter approach. PMID- 8349150 TI - Evidence supporting the superiority of intraperitoneal cisplatin compared to intraperitoneal carboplatin for salvage therapy of small-volume residual ovarian cancer. AB - PURPOSE: To examine the relative efficacy of cisplatin-based intraperitoneal (IP) therapy versus carboplatin-based IP therapy as salvage treatment of small-volume residual ovarian cancer. PATIENTS AND METHODS: We retrospectively examined the surgically defined response rates of patients with ovarian cancer treated at the Memorial Sloan-Kettering Cancer Center on four organoplatinum-based salvage IP trials (cisplatin/etoposide, cisplatin/cytarabine, carboplatin/etoposide, carboplatin/etoposide + recombinant human erythropoietin). Additional criteria for inclusion in this analysis were: (a) small-volume residual disease (microscopic disease only or largest residual tumor mass < or = 0.5 cm) when IP therapy was initiated; (b) prior response to organoplatinum-based systemic therapy; (c) laparotomy evaluation for response to the IP salvage program. RESULTS: The surgically documented complete response rate for patients with microscopic disease treated with cisplatin-based or carboplatin-based therapy was 46% (6/13) versus 38% (6/16), respectively (P > 0.25). In contrast, the surgically documented overall and complete response rates for patients with small volume macroscopic disease treated with cisplatin or carboplatin were 71% (12/17) versus 32% (6/19) (P < 0.05, chi 2 test with Yates' correction), and 41% (6/17) versus 11% (2/19) (p < 0.1), respectively. CONCLUSION: In agreement with experimental data demonstrating that the concentration of platinum within tumor is higher following equimolar doses of cisplatin, compared to carboplatin, we have observed, in this retrospective analysis, a higher surgically documented response rate for patients with small-volume residual macroscopic ovarian cancer receiving salvage cisplatin-based IP therapy. While a randomized trial will be required to definitively address the question of the relative effectiveness of the two commercially available organoplatinum agents for IP treatment of ovarian cancer, our data suggest that cisplatin is the superior agent for regional therapy in this disease. PMID- 8349152 TI - Parovarian fibroma with heterotopic bone formation of probable wolffian origin. AB - Parovarian neoplasms of wolffian duct origin are very unusual. This article presents the first report of a case of parovarian fibroma with heterotopic bone formation of probable wolffian duct origin. The tumor cells present among mature collagen bundles were fibroblast-like cells, while those at the sites of cellular proliferation were either undifferentiated mesenchymal cells or had differentiated into osteoblasts. In the bone matrix, the tumor cells had differentiated into osteoblasts and connective tissue had ossified. PMID- 8349151 TI - Uterine leiomyosarcoma and endometrial stromal sarcoma: lymph node metastases and sites of recurrence. AB - This study was undertaken to examine the incidence and conditions under which lymph node metastases are present and patterns of recurrence in women with uterine leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS), excluding malignant mixed mesodermal tumors. From 1981 through 1991, 21 women with LMS and 10 women with ESS were treated. Retroperitoneal lymph node dissections were performed in 15 women with LMS and 7 women with ESS. In the women with LMS, 4/15 (26.7%) had lymph node metastases; in each there was disseminated intra-abdominal disease. In the 7 women with ESS, there were no lymph node metastases present. Ten women (47%) with LMS developed recurrences, and 3 (14%) had persistent disease. In the 10 women with ESS, 3 (30%) had recurrences, and 1 (10%) had persistent disease. In total, recurrences involved the lung in 84% of cases. Of the 13 women with recurrences, 7 had undergone lymph node sampling, and all were negative; 4 additional women had no evidence of adenopathy on abdominal-pelvic CT scan. Lymph node metastases were found only with extrauterine disease, and in all of these cases there was rapid progression of the sarcoma. Women without extrauterine disease did not have lymph node metastases detected; however, there was still a high rate (40%) of distant failure. Knowledge of lymph node status had minimal impact on the clinical management of women with uterine LMS and ESS. PMID- 8349153 TI - Complete hydatidiform mole coexistent with a twin live fetus: clinical course of four cases with complete cytogenetic analysis. AB - Twin gestations can occur in which one twin is a normal gestation (46 chromosomes: 23 maternal and 23 paternal origin) and in which the other twin is a complete hydatidiform mole (46 chromosomes all of paternal origin). Case reports of four such combined pregnancies that presented to a single institution are provided. All cases had documentation of clinical information, cytogenetic analysis, and fetal and placental pathology. Three of the four pregnancies were terminated for medical indications despite information documenting the presence of a normal fetus. All three of these patients required subsequent chemotherapy. The fourth case was followed conservatively and resulted in the birth of a normal infant at 38 weeks gestation. We speculate that the factors that led to the need for termination of the pregnancy (aggressive growth of trophoblast) may predict the need for further therapy. A true assessment of the antenatal and malignant sequelae risks associated with these rare gestations awaits the collection of a larger series of patients. PMID- 8349154 TI - Isolated parenchymal splenic metastasis in epithelial ovarian cancer. AB - Metastatic parenchymal splenic disease in patients with ovarian cancer is unusual. It is most commonly seen in the presence of large-volume upper abdominal disease when parenchymal involvement occurs by surface extension. A patient with isolated parenchymal splenic metastasis and no peritoneal disease in the abdomen at primary surgery is described. PMID- 8349155 TI - Ovarian carcinoma presenting with inguinal metastatic lymphadenopathy 33 months prior to intraabdominal disease. AB - Ovarian carcinoma normally presents at an advanced stage of disease, with symptoms of gastrointestinal disturbances. We report a case of ovarian carcinoma presenting with metastatic inguinal lymphadenopathy which preceded any evidence of intraabdominal disease by 33 months. This is the first report of such a case. It defies the expected presentation and course of ovarian malignancies. The case is all the more rare when the incidence of inguinal node involvement in ovarian cancer is considered. The management of this patient and theoretical explanations are discussed. PMID- 8349156 TI - Squamous cell carcinoma arising in a mature cystic teratoma with metastasis to the paraaortic nodes. AB - Accurate surgical staging is critical to the management of early ovarian cancers. A patient with squamous cell carcinoma arising from a mature cystic teratoma was found to have paraaortic nodal metastasis as her only evidence of extraovarian disease. Extended field radiation therapy to the pelvis and paraaortic nodes with concomitant cisplatin and adjuvant chemotherapy failed to control her disease. Inadequate surgical staging may explain the recurrences in apparent stage I disease. PMID- 8349157 TI - Genetic risk in ovarian cancer. PMID- 8349158 TI - Interleukin-6 (IL-6) functions as an autocrine growth factor in cervical carcinomas in vitro. AB - Many factors have been implicated in the etiology of cervical neoplasia, with human papilloma virus being the latest in a long line of agents that may on their own or in combination exert various initiating and promoting effects on cervical cells, resulting in their transformation. However, for such altered cells to become invasive, it is clear that they must undergo alterations in their rate of turnover, state of differentiation, and motility. We have investigated the production of the multifunctional cytokine interleukin-6 (IL-6) by five new cervical carcinoma cell lines (XH1, EH2, DE3, JE6, and SM7) and the commercially available CaSki cell line, and have studied the effects of this cytokine on the growth of the cells in vitro. All the cell lines produce biologically active IL-6 in amounts varying between 0.35 to 2.0 ng/ml. In the presence of goat anti-sera to IL-6 all the tumor cell lines showed inhibition of growth. IL-6 acts as an autocrine growth factor for in vitro cervical tumor cell growth. PMID- 8349159 TI - DNA flow cytometric analysis of clinical stage I endometrial carcinomas with lymph node metastases. AB - Twenty-one (8%) of 264 consecutive evaluable patients with clinical stage 1 endometrial carcinoma had histologic evidence of pelvic and/or para-aortic lymph node metastases. DNA flow cytometry was performed on both the primary tumor and nodal metastasis. Seventeen of 21 sets could be analyzed. Overall, 11 (65%) of the primary carcinomas were aneuploid. Nine of 17 (53%) had consistent ploidy patterns when the primary tumor and lymphatic metastasis were compared. The remaining 8 (47%) had aneuploid primaries with diploid nodal metastases. Five (83%) of the 6 patients with diploid primary tumors were alive without evidence of disease compared to 3 of 11 (27%) patients with aneuploid tumors (P < 0.05). Other predictors of disease outcome included tumor histology, lymph vascular space invasion, and depth of myometrial invasion. Ploidy status of the lymphatic metastasis was not important in terms of overall survival. All 8 patients with para-aortic nodal metastases had aneuploid primary carcinomas compared to 4 (44%) of 9 patients with pelvic node involvement only (P < 0.01). Mean survival was 31 months for patients with para-aortic node metastases compared to 51 months for patients with only pelvic node metastases. Comparison of survival curves among these two groups demonstrated a significant survival advantage in patients with regional nodal metastases (P = 0.032). S-phase fraction of both the primary tumor and lymphatic metastasis did not correlate with survival or predict disease outcome. DNA index of the primary tumor, as a continuous variable, was inversely proportional to survival, demonstrating poorer survivorship with incremental increases of DI. Ploidy status of the lymph node metastasis was an inconsistent reflection of the primary tumor's expression and behavior and, therefore, little additional information was gained by knowledge of the lymphatic ploidy status. PMID- 8349160 TI - Evaluation of DNA ploidy in endometrial cancer. AB - We performed a study to evaluate the relationships between the surgical stage (FIGO, 1989), histological tumor grade, myometrial invasion, peritoneal cytology, lymph node metastasis and prognosis, and DNA ploidy determined by flow cytometry in paraffin-embedded blocks of resected cancer lesions from 76 patients with uterine corpus cancer (adenocarcinoma endometrial type) who had been surgically treated in our hospital. The coefficient of variation was 5.00% on average (3.40 to 5.30%) in DNA histograms of the 76 patients. DNA aneuploid was detected in 18 patients (24%) and tended to be more frequently found in association with advanced surgical stage, higher histological tumor grade, deeper myometrial invasion, positive lymph node metastasis, and positive peritoneal cytology. Kaplan-Meier method was used to analyze the relationship between prognosis and DNA ploidy in 76 patients with uterine corpus cancer, in 36 with surgical stage III, and in 26 with surgical stage IIIa, resulting in prognosis which was significantly better in patients with DNA diploid. The results of multivariate analysis also indicate that DNA ploidy is an independent prognostic factor of uterine corpus cancer. These results suggest that DNA ploidy should be an important parameter for predicting prognosis of uterine corpus cancer. PMID- 8349161 TI - Mitomycin-C plus a 3-day continuous intravenous infusion of 5-fluorouracil: an inactive salvage regimen for platinum-resistant ovarian carcinoma. AB - In a Phase II trial, patients with refractory ovarian cancer were given 10 mg/m2 mitomycin-C i.v. every 8 weeks and 1000 mg/m2/day 5-fluorouracil for 3 consecutive days by continuous intravenous infusion repeated every 4 weeks. Sixteen heavily pretreated patients with platinum-resistant disease were treated and no major responses were observed. Only 2 patients required subsequent dose reduction for myelotoxicity. No sign of gastrointestinal toxicity was seen. This regimen is inactive as salvage treatment for refractory ovarian cancer. PMID- 8349163 TI - Failure to enhance the in vivo killing of human ovarian carcinoma by sequential treatment with dequalinium chloride and tumor necrosis factor. AB - Dequalinium chloride (DECA) is a cationic, lipophilic compound with structure similar to the dye rhodamine 123. DECA is selectively accumulated and retained within the mitochondria of carcinoma cells where it acts as a mitochondrial poison by blocking mitochondrial enzymes which can then disrupt cellular energy production, eventually resulting in cell death. In this manner it is similar to the antimitochondrial effects observed with tumor necrosis factor (TNF). We have previously shown that DECA can synergize the in vitro antitumor effects of TNF against a panel of human ovarian cancer cell lines. Those drug studies have been extended to a xenogenic tumor system with a resultant increase in animal survival. Athymic mice were injected intraperitoneally with 2.0 x 10(7) PA-1 human ovarian cancer cells and DECA +/- TNF treatments begun either on Days 3 or 7 postinjection. Peritoneal tumor implantation was not histologically confirmed by Day 3 postinjection but confirmed by Day 7 following tumor cell injection. Single-agent DECA (5 mg/kg; qod) increased animal survival by 37% (P = 0.002) whereas recombinant human TNF (0.5 micrograms/mouse; qod) only increased survival by 13% (P = 0.27) relative to control animals for those animals treated 3 days post-tumor-injection. Sequential DECA/TNF enhanced animal survival by 45% (P = 0.0002) in similarly treated animals. When drug treatment was initiated 7 days following tumor injection, DECA increased survival by 23% (P = 0.04) while TNF had no effect on prolonging animal survival (3% increase; P = 0.79). Combination DECA/TNF increased survival by 23% (P = 0.04). In the UCI-101 ovarian tumor model, single-agent DECA increased survival by 28% (P = 0.04) while TNF treatment stimulated tumor growth (11% decrease in survival; P = 0.006). Combination DECA + TNF resulted in a 41% increase in survival (P = 0.003). No statistical differences were detected between survival rates for single-agent DECA vs DECA + TNF except for the UCI-101 tumor which showed potentiation due to the in vivo stimulatory effects of TNF. PMID- 8349162 TI - Absence of prohibitin gene mutations in human epithelial ovarian tumors. AB - Multiple loss of heterozygosity (LOH) studies of ovarian cancers have found a high incidence of chromosome 17 loss in these tumors. Several authors have suggested that the region commonly deleted encompasses 17q12-21. In addition, this region has recently been reported to be linked to the familial breast/ovarian cancer syndrome. Recently the human prohibitin gene was mapped to region 17q12-22. Prohibitin causes arrest of DNA synthesis by fibroblast and HeLa cells and prohibitin shows significant homology to a gene (Cc) thought to be important for the regulation of development of Drosophila melanogaster. These findings have led many to consider the prohibitin gene a potential tumor suppressor gene. In addition, sequence analysis of exon 4 of human prohibitin gene revealed mutations in 4 of 23 sporadic breast carcinomas. Because of the proposed function for prohibitin, its alterations in breast cancers, and the fact that its location on 17q falls within a commonly deleted region in ovarian cancers, we have undertaken an analysis of the sequence of prohibitin in epithelial ovarian cancers. Using several polymorphic DNA probes, we identified 20 epithelial ovarian tumors which demonstrated LOH for the region that contains the prohibitin gene. To evaluate whether mutations of prohibitin may be important in ovarian carcinogenesis, we have sequenced exons 4 and 5 of this gene using the technique of genomic amplification with transcript sequencing. Only normal exon 4 and 5 sequence was observed among the 20 tumors screened. These results demonstrate that this region of the prohibitin gene is not mutated in epithelial ovarian cancers and suggest that the prohibitin gene does not play a role in ovarian carcinogenesis. Sequencing of further exons and introns are needed to confirm this latter hypothesis. PMID- 8349164 TI - The etiology and management of diarrhea in the gynecologic oncology patient. AB - PURPOSE: We determined the etiology and evaluated the usefulness of diagnostic tests in 42 gynecologic oncology patients with diarrhea. METHODS: All inpatients who developed diarrhea during treatment for gynecologic cancer were prospectively evaluated during the 12-month study period ending June 1992. Diarrhea was defined as five or more loose stools per 24 hr lasting for 48 hr or more. Diagnostic tests were complete blood cell count; electrolytes; stool for occult blood, white blood cells, and Clostridia difficile toxin; and stool culture for Shigella, Salmonella, Yersinia, and Campylobacter. RESULTS: During the study period 351 women with gynecologic cancer received inpatient care. Forty-two (12%) patients developed diarrhea. One patient had three episodes and another had two episodes of diarrhea. There were 39 evaluable patients; 3 patients were excluded due to incomplete tests. The only cause of bacterial-associated diarrhea was C. difficile, which occurred in 4 of 39 (10.3%) patients. No patient had community acquired diarrhea, and 1 patient had diarrhea due to Crohn's Disease. Surgery was performed on 265 patients; 29 of 265 (10.9%) developed postoperative diarrhea. Eighty-six patients had medical treatment and 13 (15.1%) developed diarrhea. The distribution by admission status of patients with diarrhea did not differ statistically from the patients without diarrhea. The four patients with C. difficile-associated diarrhea received appropriate therapy at the time of diagnosis. Nevertheless, the mean (SD) duration of C. difficile-associated diarrhea (342 (103) hr) was significantly longer than the mean (SD) duration of diarrhea not associated with this pathogen (79 (32) hr). The difference between the sample means is 263 hr with a 95% confidence interval for the difference between the means of 218 and 308 hr. Electrolyte abnormalities occurred in 20 patients (51%). Fecal leukocytes were present in 11 (28%) patients and occult blood in 5 (12.8%) of the 39 patients. Neither study was predictive for the presence of C. difficile. CONCLUSION: Hospital-acquired diarrhea in gynecologic oncology patients is common, although specific bacterial pathogens requiring antibiotic therapy account for only 10% of cases. Diagnostic tests for infectious causes besides C. difficile are infrequently useful and may be omitted unless the condition persists more than 72 hr. PMID- 8349165 TI - The role of DNA index as a prognostic factor in early cervical carcinoma. AB - The value of DNA index as a prognostic factor in early cervical cancers was investigated. A total of 124 patients who underwent radical hysterectomy for stages IB-IA cervical cancers from 1/1982 to 12/1985 were included. Paraffin blocks were available in only 98 patients for the analysis. After dewaxing, rehydrating, and enzyme disaggregation, cells were subjected to dual parameter flow cytometry. Tumor DNA index was calculated and the results were correlated with 5-year survival, stage, grade, tumor size, nodal metastasis, surgical margins, and lymphovascular invasion. There were 1% hypoploid, 7.3% diploid, 72.9% aneuploid, 16.7% tetraploid, and 2.1% hyperploid. At the end of 5 years, there were 69 alive and 27 dead patients with mean DNA indices of 1.50 +/- 0.3 and 1.70 +/- 0.3, respectively. t Test analysis revealed that mean DNA index of deceased patients was significantly higher than that of alive ones (P = 0.008). Survival analysis demonstrated the prognostic significance of DNA index 1.70 (P = 0.017). Median survival of patients with DNA index of 1.70 or greater was 36 months in contrast to 73.5 months for those with DNA index less than 1.70. Multivariate analysis subsequently confirmed DNA index of 1.70 as an independent prognostic indicator with a hazard ratio of 2.05. PMID- 8349166 TI - Intraperitoneal (ip) cisplatin-mitoxantrone-interferon-alpha 2b in ovarian cancer patients with minimal residual disease. AB - Forty-one ovarian cancer patients with less than 2 cm residual disease after systemic cisplatin-based chemotherapy received 4 courses of an ip regimen including cisplatin (75 mg/m2), mitoxantrone (20 mg/m2), and interferon-alpha 2b (30 mil IU/m2). The most important side effects were abdominal pain and fatigue. Overall 15/41 patients (37%) required narcotic analgesia for severe abdominal pain. In 1 case laparotomy was necessary due to bowel obstruction. Grade 3-4 myelotoxicity was observed in 18/41 patients (28 courses). No treatment-related death occurred. Pathological complete response (pCR) was achieved in 23/37 (62%) evaluable patients. Four-year disease-free survival was 50%, and no relapse occurred after 32 months. The estimated 4-year progression-free survival (PFS) and overall survival were 35 and 60%, respectively. Patients who achieved pCR showed significantly better survival than the others (P < 0.000). At multivariate Cox's analysis pCR achievement was the most important predictor of PFS (P < 0.005) and survival (P < 0.02). Age (< or = 60 vs > 60) and CA-125 serum levels at entry (normal vs increased) also showed independent predictive value. On the basis of multivariate analysis results we created a risk model for survival and PFS based on age and CA-125 at entry. We identified three subgroups of patients with significantly different outcomes. With this new ip combination long-term disease-free survival is achieved in a significant part of ovarian cancer patients with small tumor burden. A longer follow-up is needed to see whether it can cure some of these patients, and further comparisons with other ip or systemic regimens are needed to draw definitive conclusions about its role in these patients. PMID- 8349168 TI - A comparison between loop diathermy conization and cold-knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy. AB - Eighty-six women with cervical dysplasia and unsatisfactory colposcopy were managed with excisional conization--43 with outpatient loop diathermy conization under local anesthesia and 43 matched controls with cold-knife conization as inpatients under general anesthesia. Both groups were similar in terms of age, parity, and severity of dyskaryosis on initial cytology, treatment success rates, and completeness of excision. However, loop diathermy conization was significantly quicker (2.8 +/- 2.9 min vs 14 +/- 18.6 min) and associated with less intraoperative blood loss (3.3 +/- 2.8 ml vs 79.1 +/- 74.6 ml) (P < 0.01) than cold-knife conization. Furthermore, the proportion of women with at least one complication was significantly less following loop (4.7%) than cold-knife conization (20.9%) (P < 0.05). We conclude that outpatient loop diathermy conization performed under local anesthesia is quicker and causes less intraoperative blood loss and immediate postoperative complications than cold knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy. PMID- 8349167 TI - Comparison of antigen expression on fresh and cultured ascites cells and on solid tumors of patients with epithelial ovarian cancer. AB - The antigenic phenotype of malignant cells from ascites of patients with epithelial ovarian cancers was examined and compared to that of their primary and metastatic sites. Cell-surface antigens on frozen sections of primary and metastatic tumors and frozen cell pellets from ascites were analyzed with a panel of murine monoclonal antibodies using the indirect immunoperoxidase method. In addition, ascites cells cultured with and without autologous cell-free ascitic fluid were evaluated by immunofluorescence. The pattern of antigen expression detected on fresh and cultured ascitic epithelial cells was shown to be identical to the expression in autologous solid tumor tissues. When placed in culture, malignant epithelial cells generally persisted for a minimum of one, but no more than five, passages. Addition of autologous ascitic fluid to cultures of ascites cells did not alter the phenotype of the epithelial tumor cell population and did not enhance the growth of these cells. From one culture of ascites cells a permanent malignant epithelial ovarian cancer cell line (designated SK-OV-8) was established. The demonstration that epithelial tumor cells found in ascites of patients with epithelial ovarian cancer have the identical antigenic phenotype as their solid tumor counterpart, at least for the panel of antigens studied, may be useful in planning imaging and therapeutic trials with monoclonal antibodies. PMID- 8349169 TI - Aborted exenterative procedures in recurrent cervical cancer. AB - Preparation for pelvic exenteration is a traumatic experience for every patient, especially so when the procedure has to be aborted because of advanced disease. This occurred in 111 of 394 patients who underwent exploration for possible pelvic exenteration for recurrent cervical cancer at the University of Texas M. D. Anderson Cancer Center between 1970 and 1990. We reviewed these cases to better delineate preoperative factors predictive of unresectability. Distributions of initial stages and pathological diagnoses were similar to those for all cases of primary cervical cancer. The median time from primary therapy to recurrence was 12 months. The reasons for aborting the procedure included the presence of peritoneal disease in 49 patients (44%), for which the only preoperative finding with significant correlation was the presence of a pelvic mass (P = 0.03). Other reasons for aborting the procedure included nodal disease in 45 patients (40%), related to a short interval from primary therapy (P = 0.008) and the notation of fibrosis on preoperative exam (P = 0.01), parametrial fixation in 15 patients (13%), and hepatic lesions or bowel involvement in 5 patients (4.5%). Peritoneal cytology was negative in 61 of 79 patients (77.2%) and was of predictive value only in patients with adenocarcinoma. In conclusion, disseminated disease can seldom be detected during preoperative work-up. Evaluation of nodal status with computed tomography, lymphangiogram and directed fine-needle aspiration, and examination of peritoneal cytology in cases with adenocarcinoma, are the best available means of reducing the number of aborted procedures. PMID- 8349171 TI - Immunoreactive endothelins in human follicular fluid. AB - Endothelin levels were measured by means of [125I]endothelin-1,2,3 radioimmunoassay in the follicular fluids of 22 mature ovarian follicles of 11 patients, obtained during ovum pickup. In all but 1 of the follicles, endothelin levels were detectable and ranged between 0.2 and 3.6 pg/ml (mean 1.47 +/- 0.99). In this preliminary study, no correlation was found between follicular endothelin levels and oocyte fertilization or the hormonal ovarian response during the follicular phase. PMID- 8349170 TI - Relationship between mean arterial pressure and parameters derived from blood flow velocity waveforms in the systemic circulation of fetal sheep. AB - In 8 fetal sheep under anesthesia, we examined the relationship between the fetal aorta blood flow velocity waveform and fetal mean arterial pressure after administration of norepinephrine and angiotensin II. It was hypothesized that the pulsatility index (PI) of the waveform would change during fetal hypertension. Measurements were performed using a 20-MHz Doppler transducer on the aorta directly beneath the diaphragm and a catheter inserted via the femoral artery into the abdominal aorta. Further instrumentation included a Doppler transducer and an electromagnetic flowmeter on the common umbilical artery and a catheter in the inferior vena cava. Fetal hypertension was induced by bolus administration of either norepinephrine or angiotensin II or by infusion of norepinephrine. With the Doppler transducer on the common umbilical artery, it was possible to study external iliac artery blood velocity waveforms in 4 fetal lambs, whereas aorta blood velocity waveforms were recorded in 7 fetal lambs. The measurements of external iliac artery PI and mean arterial pressure were characterized by a linear regression with a correlation coefficient of 0.72, whereas the measurements of aorta PI and mean arterial blood pressure were characterized by a linear regression with a correlation coefficient of 0.40. However, notable changes were observed in the aorta blood velocity waveform, which were not expressed by a substantial increase in the aorta PI. These changes can be described as a narrowing of the systolic peak and an earlier occurrence of the first dicrotic notch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349172 TI - Ambivalence during early pregnancy among expectant mothers. AB - Ambivalence during the early stages of pregnancy is a known phenomenon, among expectant mothers as well as among applicants for abortion. The conflict of wanting or not wanting to have a child must be solved in the decision-making process that precedes the choice of whether to interrupt a pregnancy or carry it to full term. The time limit for this decision making process is reduced by the medical abortion methods now available. Hasty early abortions as well as delayed abortions create problems and should be avoided. The present Swedish study, based on 123 semistructured interviews conducted among expectant mothers, focuses on this ambivalence during early pregnancy. Fifty-five percent of the interviewees reported that the current pregnancy was planned, 14% had become pregnant in spite of using contraceptives. Fifteen percent had considered an abortion during the current pregnancy. Ten in-depth interviews revealed how women contemplating abortion dealt with their ambivalence and finally decided to continue the pregnancy. The study shows that no one but the pregnant woman herself can arrive at the informed analysis necessary for a well-considered decision about the future of her pregnancy. However, all pregnant women should be offered the opportunity to talk about their situation, their thoughts and feelings to a neutral listener, in order to make that decision. PMID- 8349173 TI - Collagenolytic effect of disintegrated bacterial cell extracts on the human amniotic membrane at term pregnancy. AB - Bacterial ascending from the cervix may infect the membranes and amniotic fluid, contributing to their premature rupture. In the present in vitro study, isolated amniotic membranes were exposed to different concentrations of disintegrated bacterial cells. Collagenolysis was estimated by the ratio of acid soluble/insoluble hydroxyproline. The amniotic membrane proteins were separated by electrophoresis after incubation with 14C proline and disintegrated bacterial cells. The proportion of soluble hydroxyproline increased with the bacterial concentration used, and the radioactivity decreased in proteins of the 30- to 80 kD range. The data support the notion that bacteria contain collagenolytic enzymes affecting human amniotic membranes. PMID- 8349174 TI - Serum levels of creatine kinase and its isoenzymes during the 1st postpartum day in healthy newborns delivered vaginally or by cesarean section. AB - The purpose of this study is to investigate the relationship of creatine kinase (CK) and its isoenzyme levels in the newborn to the mode of delivery, time interval from birth (divided in four 6-hour time periods), parity and sex of the neonates. During the 1st postpartum day, serum levels of CK and its isoenzymes (CK-MM, CK-MB, CK-BB) were determined from 115 healthy full-term neonates born consecutively either by spontaneous vaginal delivery (VD, n = 85) or by elective cesarean section (CS, n = 30). The multiple regression analysis was applied. Total CK levels were positively correlated with VD (p < 0.0003). This was mainly attributed to a rise in the CK-MM activity which presented a similar pattern to CK. CK-MB activity was also positively correlated with VD. In contrast, CK-BB was negatively correlated to the postpartum time period. Neonatal sex and parity did not influence CK and its isoenzyme levels significantly. In conclusion, VD contributes significantly to an increase in CK levels during the 1st day of extrauterine life. PMID- 8349175 TI - Effects of testosterone on the development of endometrial tumors in female rats. AB - Long-term treatment of mature virgin female rats with a high dose of testosterone (24 weeks at a total dose of 300 mg) was associated with the development of endometrial adenomatous hyperplasia and resulted in a high incidence of adenocarcinoma when administered in combination with 7,12-dimethyl benz[a]anthracene (DMBA; 2 mg in 0.1 ml sesame oil) introduced into the uterine cavity. Adenomatous hyperplasia occurred in all testosterone-treated rats, both with and without ovaries. Testosterone may promote the induction of endometrial tumors by DMBA. PMID- 8349176 TI - Developmental steps for radionuclide hysterosalpingography. AB - The active oviductal transportation capacity was studied in 73 infertile women by the use of a new deposition technique of radioactive particles into the internal cervical os. The main reason for this study was that a previous observation had shown that such a transportation capacity was lacking in 41% of the infertile patients with a normal hysterosalpingogram. The examination was performed in the immediate preovulatory phase, i.e. on days -3 to 0 before the ovulation, as measured by the basal body temperature during two preceding cycles. The deposition of 99mTc-labelled albumin particles of 0.2-1.0 micron at the internal cervical os and the interpretation of the radionuclide images are described in detail. The results show that the bilateral active tubal transportation capacity was present in 42 patients. An impaired transportation capacity was diagnosed in 22 patients. In 9 patients, the particles never reached the uterine cavity, or all activity leaked back to the vagina. PMID- 8349177 TI - Tumor necrosis factor in plasma and peritoneal fluid of women with and without endometriosis. AB - To determine whether in vivo levels of tumor necrosis factor a in plasma and peritoneal fluid differ in infertile subjects with and without endometriosis, peripheral blood and peritoneal fluid samples were collected in 94 women undergoing laparoscopy for infertility. Quantitative determinations of tumor necrosis factor a were performed by an enzyme immunoassay test. Tumor necrosis factor a levels were below the detection limit (10 pg/ml) in plasma and peritoneal fluid of 42 (91%) and 30 (90%) patients with endometriosis and 40 (83%) and 31 (91%) subjects without the disease, respectively. In our series, plasma and tumor necrosis factor a levels were not different in infertile women with and without endometriosis. PMID- 8349178 TI - Natural volume handwashing urethrocystometry: a physiological technique for the objective diagnosis of the unstable detrusor. AB - A group of 163 patients attending with a naturally full bladder had urethrocystometric assessment during provocation with a handwashing test. The results were compared with those from a similar group of 169 patients who were subjected to a handwashing test following the infusion of 500 ml of saline with fast-fill cystometry. The latter group was found to have an unacceptably high number of false-positive results. Also, the results appear to indicate that urine loss due to uncontrolled detrusor contraction may be mainly due to premature activation of the micturition reflex. A fall in the intraurethral pressure was found in 79% and a rise in detrusor pressure in 49% of the patients presenting with a prior history of an unstable bladder. Natural urethrocystometry appears to be a useful and informative technique for objectively assessing patients with a prior history of bladder instability. PMID- 8349179 TI - Effects of hyaluronate, strontium and prolonged incubation on different sperm parameters. AB - The aim of this study was to evaluate the effect of hyaluronate and strontium with short and prolonged incubation periods on different sperm parameters. For sperm intended for in vitro fertilization good progressive motility, a high percentage of normal form, a suitable linear velocity and a low acrosome-reacted proportion of sperm are required. The semen washing procedure in the self migration method with medium containing hyaluronate Ca2+ after 3 h of incubation complies better with these criteria. PMID- 8349180 TI - Magnetic resonance imaging angiography in a case of eclampsia. AB - We experienced a typical case of eclampsia. After the onset of eclampsia, we performed magnetic resonance imaging angiography (MRI angiography) to estimate the function of the cerebral artery. MRI angiography showed that spasm occurred in many cerebral arteries. The spasm was still observed in some arteries 13 day after the onset of eclampsia. Vasospasm of eclampsia was clearly, easily and noninvasively confirmed in this case by MRI angiography. This observation suggests that MRI angiography is very useful and informative for diagnosis and in treatment of eclampsia. PMID- 8349181 TI - Transvaginal sonography in the diagnosis and management of cervical incompetence. AB - Cervical incompetence remains a controversial area in obstetric management. The development of transvaginal sonography has resulted in a clearer image of the internal cervical os, a development which may indirectly have beneficial effects on outcome. However, the rapid development of cervical dilatation in some cases necessitates frequent ultrasound monitoring. PMID- 8349182 TI - Involvement of the local immune response in a case of advanced cervical cancer in a patient with systemic lupus erythematosus. AB - Although patients with systemic lupus erythematosus (SLE) have frequently accompanying malignancies, there are few documented cases in the literature of advanced cervical cancer patients with SLE. This report describes a case of advanced cervical cancer in a 39-year-old patient with a 20-year history of SLE (FIGO stage IIIb) and evaluates the immunological response of the tumor. The clinical course of this patient with SLE, with rapid growth of cervical cancer and a poor prognosis, may suggest that T cells play a key role in the growth of cancer. PMID- 8349183 TI - Effect of smoking on maternal glucose metabolism. AB - Maternal smoking, studied in late pregnancy, was found to be associated with lower blood glucose values, both during fasting and after an intravenous glucose load. As a correlation between blood glucose levels and infant birth weight has been reported, it is possible that smoking during pregnancy might reduce fetal growth through an effect on maternal glucose metabolism. PMID- 8349184 TI - Cryopreservation of human platelets using dimethyl sulfoxide and glycerol glucose: effects on "in vitro" platelet function. AB - BACKGROUND: The technique of freezing blood platelets could be very useful in the transfusion support of thrombocytopenic patients. The best method of platelet cryopreservation still remains an object of debate, though it has been suggested that dimethyl sulfoxide (DMSO) is more effective than glycerol-glucose as a cryopreservative. However, few studies have directly compared platelets cryopreserved with different methods. METHODS: We compared "in vitro" function of platelets cryopreserved with 5% dimethyl sulfoxide (DMSO) or 3% glycerol-glucose at -140 degrees C. Platelet aggregation and release reaction were studied with a Lumi aggregometer, thromboxane B2 (TxB2) production by radioimmunoassay, and Ca++ movement by the Fura 2 method. RESULTS: Cryopreservation with both of the methods dramatically reduced the ability of platelets to release ATP and to aggregate in response to single agonists. In contrast, cryopreserved platelets maintained their ability to aggregate after stimulation with paired agonists and to produce TxB2. Cytoplasmic Ca++ increase induced by thrombin was observed in the glycerol preserved platelets, while it was nearly absent in the DMSO-preserved ones. CONCLUSIONS: We suggest that cryopreservation with glycerol-glucose or DMSO induces similar defects of platelet function. The damage is severe, but platelets are still able to respond to strong stimulation. PMID- 8349186 TI - Use of recombinant human erythropoietin (rh-EPO) in the treatment of anemia in hemodialysis patients: a multicenter Italian experience. AB - BACKGROUND AND METHODS: After the phase I-II clinical trials in 1986, several studies on the use of rHuEPO in the treatment of anemia of renal failure have been carried out and the drug has been introduced into clinical practice. In the present article we analyze the results of recombinant human erythropoietin (rh EPO) therapy administered intravenously (i.v.) to 759 patients in several italian dialysis centers. RESULTS AND CONCLUSIONS: Data analysis confirms the erythropoietic efficacy of the drug (mean Hct increase from 22.1 +/- 2.8 to 31.5 +/- 3.0%) as well as the generalized Italian position toward a cautious correction of anemia (the increase is achieved in 6 months). Such a therapeutic approach is consistent with the chronic anemia of the dialysis patient. Low doses are widely used (40-100 IU/kg x three times a week). Analysis of adverse events seems to point out that some correlate directly with the drug and are therefore difficult to eliminate (flu-like syndrome). On the other hand, certain adverse events seem to correlate with the modalities of drug use (dosage, time required for the Hct increase). The possible advantages of subcutaneous administration are also described. PMID- 8349185 TI - Reduction of plasma fibrinolytic activity following high-dose cyclophosphamide is neutralized in vivo by GM-CSF administration. AB - BACKGROUND: GM-CSF has broad clinical applicability as a potent myelopoietic stimulator. However, its function is not restricted to the myelopoietic system and several observations suggest that GM-CSF may interfere with the hemostatic balance. In order to assess whether GM-CSF has any influence on hemostasis, we evaluated some coagulative and fibrinolytic parameters in patients treated with GM-CSF following chemotherapy. METHODS: Fibrinolytic activity (FA), fibrinogen and D-dimer were evaluated before and after high-dose cyclophosphamide in 6 patients additionally treated with GM-CSF and in 5 control patients; moreover, tissue plasminogen activator (tPA) was assayed in those treated with GM-CSF. Comparative in vitro analysis was performed on cultured endothelial cells before and after exposure to GM-CSF. RESULTS: Control patients showed a significant decrease in plasma FA after chemotherapy compared to basal values (FA/mm2: 15.6 +/- 2.1 at day + 2 and 20.8 +/- 19 at day + 4 vs. 103.8 +/- 64.2 at day 0; p < 0.005); conversely, no FA reduction was observed in GM-CSF-treated subjects. In this latter group a marked increase in tPA antigen was seen, consistent with enhanced FA. No significant changes in plasma D-dimer and fibrinogen values were detected in the two groups. tPA, urokinase-type plasminogen activator, PAI-1 and procoagulant activity were evaluated in vitro on cultured human endothelial cells and found to be unchanged following GM-CSF addition. CONCLUSIONS: The results demonstrate that high-dose chemotherapy may negatively influence plasma FA. This adverse side effect is neutralized by GM-CSF administration. The discrepancy found between in vitro and in vivo GM-CSF activity on hemostatic may be explained by in vivo GM-CSF stimulation of cell types other than endothelial cells. PMID- 8349187 TI - Serum erythropoietin level and marrow erythroid infiltration predict response to recombinant human erythropoietin in myelodysplastic syndromes. AB - BACKGROUND AND METHODS: In 38 patients with myelodysplastic syndromes (MDS) the values of serum erythropoietin were measured at diagnosis and compared with the haemoglobin level. A highly significant inverse relationship was found between these two parameters, suggesting that the physiologic mechanism of erythroid progenitor cell recruitment is preserved in MDS. Fourteen transfusion-dependent patients were treated with recombinant human erythropoietin at the dose of 150 U/Kg three times weekly for at least 2 months. RESULTS AND CONCLUSIONS: Under recombinant human erythropoietin, three patients became transfusion-independent and 5 had a transient decrease of their transfusion requirement. Two patients under prolonged treatment at the same dose of erythropoietin remain in complete remission after 12 and 15 months respectively. A direct relationship between response to erythropoietin treatment and degree of bone marrow erythroid hyperplasia, coupled to an inverse correlation between response to erythropoietin and baseline serum erythropoietin levels were noted. Based on these findings, recombinant human erythropoietin may represent an effective treatment modality for selected patients with MDS. PMID- 8349188 TI - Recombinant human erythropoietin in the treatment of myelodysplastic syndromes. An interim report. AB - BACKGROUND: It has recently been demonstrated that erythropoietin increases hemoglobin levels in anemia secondary to chronic renal failure. Some recent experiences have suggested a possible role in the treatment of anemia in patients with myelodysplastic syndrome (MDS). METHODS AND RESULTS: From April, 1990 to March, 1991, 16 patients (11 males and 5 females, median age 58.5 years) affected by low-risk myelodysplastic syndromes (MDS) were treated with recombinant human erythropoietin (rHuEPO) to ameliorate Hb levels and reduce transfusional requirement. All patients received high doses of rHuEPO (400 U/Kg s.c. twice weekly for 3 months). A partial response, defined as a stable increase in Hb levels > 1g/dL and/or a reduction in transfusional need > 50% lasting at least 3 months, was achieved by 5/16 patients. Those who responded received an additional course of treatment with rHuEPO at an increased dosage (600 U/Kg twice weekly for 3 months), and one of these five showed a progressive rise in Hb level up to normalization, while the other 4 remained stable. The treatment was well tolerated and no adverse reactions were observed. CONCLUSIONS: These results suggest that some patients with MDS may benefit from rHuEPO treatment. PMID- 8349189 TI - Transient aplasia preceding adult acute lymphoblastic leukemia. AB - A 62-year-old woman developed common acute lymphoblastic leukemia (ALL) after spontaneous recovery from transient marrow aplasia. Although the mechanisms underlying bone marrow suppression in acute leukemia are obscure, it is important to know that transient aplasia may be observed as a prodromal feature in ALL in adult patients as well as in children. PMID- 8349190 TI - Gaucher's disease associated with monoclonal gammapathy of undetermined significance: a case report. AB - We report a case of adult-type Gaucher's disease associated with monoclonal gammapathy of undetermined significance. Bone marrow infiltration by Gaucher's cells and spleen infiltration by Gaucher cells and plasma cells was observed on cytohistologic examination. Splenectomy induced complete recovery of cytopenias and a marked reduction of the monoclonal protein. PMID- 8349192 TI - Thrombocytopenic purpura and hepatitis C virus infection. PMID- 8349191 TI - Leukemic dermal infiltrate at the exit site of a central venous catheter. AB - This report describes the case of a minimally differentiated acute myeloid leukemia (FAB M0) diagnosed in a 55-year-old woman. During a second chemotherapy induced complete remission, a subcutaneous nodule appeared at the scar of a recently removed Hickman catheter, which when biopsied revealed leukemic infiltration of the dermis and hypodermis. The patient had a bone marrow relapse three weeks later. The authors review similar recent reports and emphasize the importance of recognizing this particular type of cutaneous leukemic relapse. PMID- 8349193 TI - Eosinophilic leukemia and classical Kaposi's sarcoma: a serious combination of illnesses. PMID- 8349194 TI - Immune reconstitution after bone marrow transplantation: expansion of primed/memory T cells rather than recapitulation of ontogeny. PMID- 8349195 TI - Control of erythropoietin production in man. PMID- 8349196 TI - Pyruvate kinase (PK) deficiency in Jordan. AB - BACKGROUND AND METHODS: The clinical and biochemical aspects of two cases of PK deficiency associated with chronic hemolytic anemia in two unrelated patients are reported. The residual erythrocyte PK enzymes in both patients were characterized by the recommended methods of the International Committee for Standardization in Hematology (ICSH). RESULTS AND CONCLUSIONS: Patient (W.Q.) had 60% residual PK activity and may be considered homozygous on the basis of consanguinity in the family. This patient suffered from moderate hemolytic anemia that improved after splenectomy. The enzymatic properties were: low activity, moderate thermal stability, reduced affinity for phosphoenol-pyruvate (PEP), and normal electrophoretic mobility. Patient (E.O.) had 42% residual PK activity and may be considered compound heterozygous since his parents are not related. He suffered from moderate hemolytic anemia. The enzymatic properties were: low activity, moderate thermal stability, reduced affinity for PEP and minimal retardation in electrophoretic migration. Theses two cases of PK deficiency are the first to be discovered in Jordan and probably the first in any Arab country. PMID- 8349197 TI - Vitamin B12 transport proteins in patients with HIV-1 infection and AIDS. AB - BACKGROUND: Low vitamin B12 levels (B12) are often observed in patients infected with human immunodeficiency virus type 1 (HIV-1). The causes underlying this finding are thought to be intestinal malabsorption and/or abnormalities in the vitamin plasma binding proteins (BP). MATERIAL AND METHODS: Serum levels of B12 and BP were studied in eighty HIV-1-positive patients, 55 of whom met the diagnostic criteria for AIDS. Subjects were divided into various subgroups: non AIDS HIV-1 positive versus AIDS; low serum B12 levels (DB12, < 150 pmol/L) versus normal serum B12 levels (NB12); and the results obtained were compared both between groups and with respect to a reference population (RF) of normal volunteers. RESULTS: Low levels of serum B12 were found in 14 patients (17.5%), without differences between the AIDS and non-AIDS subgroups. The levels of holohaptocorrin (holoHP) were lower in the DB12 group than in the NB12 and RF groups (p < 0.01), and no differences were found between the AIDS and non-AIDS groups. The levels of apotranscobalamin (apoTC) were higher in the AIDS group than in the non-AIDs and RF subjects (p < 0.01), but no differences were found between the DB12 and NB12 groups. Likewise, no differences were noted in the levels of holoTC between the DB12 and NB12 groups. A positive correlation between neutrophil counts and free serum haptocorrin levels (apoHP) (rs = 0.36; p = 0.002), and a negative one between the former and the levels of apoTC (rs = -0.3; p = 0.009) were observed. Furthermore, a positive correlation was detected between the erythrocyte sedimentation rate and the levels of apoHP and TC. CONCLUSIONS: Low serum levels of HP in HIV-1 positive patients could lead to the low levels of serum vitamin B12 frequently observed in this patient population, while the high levels of TC could merely represent a non-specific marker of inflammation (acute phase, reactant). PMID- 8349198 TI - A two-generation reproduction study in rats with methyl bromide-fumigated diets. AB - Crj:CD(SD) rats were fed basal (control) diet or methyl bromide-fumigated diet containing 80, 200 or 500 ppm total bromine for two successive generations (18 wk for each generation). Compared with controls, food consumption was significantly lower in F1 parental females of the 500-ppm group during the second half of the dosing period, and F2 female pups of the 500-ppm group showed lower body weights throughout the lactation period. No other treatment-related changes were found at any dietary level of total bromine in either parental animals (F0, F1) or their offspring (F1, F2) for any of the parameters studied (i.e. clinical signs, oestrous cycle, sperm count and morphology, mating, fertility, gestation, parturition, litter size, pup viability, organ weights, and gross or histopathological examination). It was concluded that residues of 200 and 500 ppm total bromine in diets fumigated with methyl bromide are the no-observed-effect level and the minimum toxic level, respectively, for both parental rats and their offspring, and that bromine residues do not affect reproductive performance at dietary levels of up to 500 ppm. PMID- 8349199 TI - Effect of oral aluminium citrate on short-term tissue distribution of aluminium. AB - Aluminium (Al) concentrations in the plasma, bone, lung, liver, kidney, spleen, duodenum and brain of rats were measured 2, 4 and 24 hr after a single oral dose of 0.46 mmol as Al citrate (1:5 molar ratio). Compared with control animals, very high concentrations were found at 2 hr post-administration in plasma (539 micrograms/litre) and in all tissues except the brain where Al did not change throughout the 24-hr period. The increased levels in the liver (161 ng/g) and lung (89.7 ng/g) at 2 hr were maintained until 4 hr and then decreased. At 24 hr the plasma value decreased to 24.6 micrograms/litre as compared with the peak value of 539 micrograms/litre. In a typical soft tissue such as the kidney the peak at 2 hr of 682 ng/g decreased to 241 ng/g, which was still more than 10-fold greater than the control level. Uniquely, in the case of bone Al increased throughout the period of the experiment. Our results indicate that Al in the citrate form is readily absorbed and that it appears to equilibrate rapidly between plasma and the intracellular compartments of most soft tissues but does not readily permeate the blood-brain barrier. In a group of rats previously given silicic acid in the drinking water and co-administered with the Al dose, the tissue Al distribution pattern at 4 hr post-administration was modified in comparison with the test animals not loaded with silicic acid. Al concentrations in plasma and soft tissues were significantly reduced except for the spleen, in which Al increased, and there was complete inhibition of the very high Al uptake/deposition in bone. PMID- 8349200 TI - Histological and serum biochemical effects of 1-isothiocyanato-3- (methylsulphinyl)-propane in the F344 rat. AB - 1-Isothiocyanato-3-(methylsulphinyl)-propane (IMSP or iberin) is one of the major glucosinolate hydrolysis products found in cruciferous vegetables. The toxicity of IMSP after oral administration is unknown. This study examined the histological lesions and serum biochemical alterations resulting from intragastric administration of IMSP to male Fischer F344 rats. Rats were administered IMSP in corn oil by gavage at concentrations of 0.1, 0.3, 0.6, 1.0 and 2.0 mmol/kg body weight. Rats were anaesthetized and exsanguinated, and perfusion fixed at 4, 24 and 72 hr after dosing. IMSP caused a dose-dependent decrease in body weight for the first 24 hr after dosing. Multifocal haemorrhages and erosions of the mucosal portion of the stomach were grossly and histologically evident after 4 hr in rats dosed with more than 0.3 mmol IMSP/kg body weight, with severity increasing with dose. Mucosal lesions resolved by 72 hr in all but the 2 mmol/kg group. No significant lesions were observed in the liver or kidney. No physiologically significant haematocrit, electrolyte, blood urea nitrogen, creatinine or serum enzyme activity changes were observed. Urine collected after a dose of 1 mmol IMSP/kg body weight accounted for 1% of the IMSP, demonstrating that the compound was absorbed from the gastro-intestinal tract. PMID- 8349201 TI - Contribution of phenolic and quinonoid structures in the mutagenicity of the edible mushroom Agaricus bisporus. AB - The objectives of this work were to establish the contribution of agaritine in the mutagenicity of ethanolic extracts from Agaricus bisporus and to examine the possible involvement of phenolic and quinonoid compounds in the mutagenic response to mushrooms. The mutagenic profile of agaritine in the Ames test, in the absence of an activation system, was different from that of the mushroom ethanolic extracts. Incorporation of rat hepatic cytosolic fractions as the activation system increased the mutagenicity of the mushroom ethanolic extracts in Salmonella typhimurium strain TA 104 but did not influence the mutagenicity of agaritine. It was concluded that agaritine is not the principal mutagenic component in the mushroom. The cytosol-induced mutagenicity of the mushroom extracts required NADPH, and was inhibited by dicoumarol and menadione. Moreover, the mutagenic response in the presence of cytosolic fractions was inhibited by superoxide dismutase, catalase, glutathione and dimethyl sulfoxide, thus implicating reactive oxygen species. Finally, tyrosinase, the enzyme converting mushroom phenols to quinones, increased the mutagenicity of the mushroom extracts. Collectively, the above results indicate that phenolic and quinonoid compounds, presumably through the generation of reactive oxygen species, may play a significant role in the mutagenicity of mushroom extracts. PMID- 8349202 TI - Percutaneous absorption of diazinon in humans. AB - Diazinon is an organophosphorus insecticide which, through general use, comes into contact with human skin. To investigate its percutaneous absorption, human volunteers were exposed for 24 hr to 14C-labelled diazinon applied in acetone solution (2 micrograms/cm2) to the forearm or abdomen, or in lanolin wool grease (1.47 micrograms/cm2) to the abdomen. Complete void urine samples were collected daily for 7 days. Percutaneous absorption ranged from 2.87 +/- 1.16% (mean +/- SD, n = 6) to 3.85 +/- 2.16% of the applied dose, and there were no statistically significant differences with regard to site or vehicle of application. In rhesus monkeys, over the 7 days after iv dosing (2.1 microCi [14C]diazinon, 31.8 micrograms) a total of 55.8 +/- 6.8% (n = 4) of the dose was excreted in the urine, and 22.6 +/- 5.2% was eliminated in the faeces (78.4% total accountability). In in vitro percutaneous absorption studies with human abdominal skin, 14.1 +/- 9.2% of the applied dose accumulated in the receptor fluid over 24 hr of exposure to 0.25 microgram/cm2 (acetone vehicle). The calculated mass absorbed was the same (0.035 microgram/cm2) for both in vitro and in vivo absorption through human skin. PMID- 8349203 TI - Effects of nivalenol on hepatic drug-metabolizing activity in rats. AB - Effects of nivalenol (NIV), a trichothecene mycotoxin, on hepatic drug metabolizing activity and aflatoxin B1 (AFB1) metabolism were investigated in male rats. In rats fed the diets containing 6-12 ppm NIV for 2 or 4 wk, decreases in initial feed uptake, terminal weight gain and organ weights were evident. An increase in cytochrome P-450 activity was observed in the hepatic microsomes, and Western blot analysis revealed a transient increase in P4502B1/2, together with a slight induction of P4501A2. The activity of cytosolic glutathione S-transferase (GST) enzymes was also enhanced in the rats, and Western blot analysis demonstrated an elevation of GST 1-2. The formation of aflatoxin B1-DNA adducts (AFB1-DNA) was increased in experiments using hepatic microsomal preparations from rats fed the NIV diet, whereas supplementation with cytosol prepared from NIV-treated rats reduced the microsomal potential for adduct formation. In in vivo experiments, the AFB1-DNA concentration in NIV-treated rats was lower than that in the controls. These results suggest that activities of cytochrome P-450 and GST enzymes were increased in rats fed NIV for several weeks. Alteration of these phase I and phase 2 enzyme levels resulted in the modulation of AFB1 adduction to DNA in vitro and in vivo. PMID- 8349204 TI - Effect of red palm oil on some hepatic drug-metabolizing enzymes in rats. AB - Red palm oil (RPO) from Elaeis guineensis is being considered for use as an edible oil in India as it is one of the richest natural sources of carotenoids. The effect of RPO on the host detoxification system, which is a vital mechanism in cancer prevention, was studied in three separate batches of Wistar/NIN inbred albino rats, and compared with controls, groundnut oil (GNO) and refined bleached deodorized palmolein oil (RBDPO). The first batch of 36 rats (12 from each group) comprised the adult males (26 wk old) of the third generation (F2b) from a multigeneration reproduction study in which three groups were fed 10% GNO or RPO or RBDPO for three generations continuously. Phase II glutathione-S-transferase (GSH-T) activity was measured in the liver cytosol of these rats after they had twice completed the process of mating, gestation, lactation and weaning, because GSH-T is one of the principal detoxifying enzymes involved in conjugating reactions of phase II metabolism. The fourth generation (F3b) weanling rats of the three groups, receiving GNO, RPO or RBDPO, were continued on the 10% oil diet for 9 wk, after which cytosolic GSH-T activity was measured. In the second experiment, eight male weanling Wistar/NIN inbred albino rats, 5 wk old, weighing 100-120 g, were fed 10% GNO, RPO or RBDPO for 4 wk in a 20% protein synthetic diet. Liver cytosolic GSH-T, reduced glutathione, microsomal total cytochrome P 450, aminopyrine N-demethylase and ethoxyresorufin-O-deethylase activity were measured to elucidate the effect of RPO on some phase I and phase II reactions. Significantly higher levels of GSH-T were observed in F2b and F3b rats given RPO than in those given GNO or RBDPO. In the second experiment, GSH-T induction was also noted, together with increased levels of reduced GSH. Phase I enzymes and total cytochrome P-450 levels were comparable between groups, indicating that no induction attributable to RPO had occurred. Thus, enhancement of one of the detoxifying phase II enzymes, in conjunction with the lack of induction of those activating phase I enzymes that are known to metabolize phenobarbitone and polycyclic aromatic hydrocarbons, suggests that RPO affords protection against chemical carcinogens, probably because of its carotenoid content. PMID- 8349205 TI - Cu(II)-dependent degradation of DNA by riboflavin. AB - Riboflavin, in the presence of Cu(II), caused breakage of calf thymus DNA and supercoiled pBR322 plasmid DNA. The rate of such DNA degradation was several times greater than that caused by riboflavin alone. The reaction was inhibited under anaerobic conditions, but oxygen could be replaced by the addition of H2O2. Riboflavin reduced Cu(II) to Cu(I), which was shown by using the Cu(I) sequestering reagent neocuproine, to be an essential intermediate in the DNA degradation reaction. Results obtained with scavengers of active oxygen species and their production by riboflavin and Cu(II) indicated that the species predominantly responsible for DNA breakage is singlet oxygen. PMID- 8349206 TI - Microdiffusion method with solid state detection of cyanogenic glycosides from cassava in human urine. AB - A method for quantitative determination of cyanogenic glycosides in human urine is described. It is based on enzymatic cleavage of the glycosides, microdiffusion of the hydrogen cyanide formed, solid state detection by colour formation on a picrate-impregnated sheet, and subsequent rating of the coloured spot by the absorption of transmitted light at 540 nm with a thin-layer (TLC) densitometer. The method has been tested using normal as well as pathological urines containing glucose, protein, leucocytes, blood and bacteria. The method allows quantification of urinary linamarin above 70 mumol/litre, in 40 microliters urine. In Mozambican subjects consuming insufficiently processed cassava the mean urinary linamarin levels were 211 mumol/litre, indicating for the first time that substantial amounts of the main cyanogenic glycoside in cassava may be absorbed from the human gut and excreted intact in the urine. PMID- 8349207 TI - Management of metatarsus adductovarus. AB - A retrospective analysis of 795 patients treated for metatarsus adductovarus by a standardized outpatient approach by one of the authors (D.S.W.) from 1970 to 1983 was conducted to evaluate the efficacy of a straight metal bar and attached reverse last shoe protocol. Criteria for inclusion were developed excluding those milder cases in which spontaneous resolution was expected and indeed occurred. Nearly uniform excellent results were encountered, with a 99% likelihood of obtaining a fully corrected foot. Surgical intervention was deemed necessary in under 1% of cases seen. The authors also examined birth weights and rank in relation to metatarsus adductovarus. Those children with the deformity had a mean birth weight of 7.6 pounds, without statistical variance from normal average birth weights. We were unable to establish any statistical association with birth rank. In light of the results of this study, which compare favorably with serial casting, we recommend this approach as a more economical and less disruptive and cumbersome technique for parent, patient, and physician. PMID- 8349208 TI - Distal blood pressure as a predictor for the level of amputation in diabetic patients with foot ulcer. AB - The predictive value of distal blood pressure measurements for the level of amputation was studied prospectively in 161 consecutive diabetic patients with foot ulcers. The patients were treated as outpatients except for periods of surgery and when complications requiring hospital care occurred. All patients were treated pre- and postoperatively by the same multidisciplinary foot care team. Either ankle or toe blood pressure measurement was available in 86% of the patients. Incompressible arteries, ulcer or gangrene at the measuring site, previous amputation, poor general condition, and an emergency situation were factors that excluded standardized ankle and toe blood pressure measurements in 24% and 27% of the patients, respectively. An absolute lower ankle pressure level of 50 mm Hg was found, below which a minor amputation was never sufficient to achieve healing. An ankle pressure below 75 mm Hg was seldom sufficient, and at or above that pressure level, the ankle pressure had no predictive value in this respect. At a toe pressure below 15 mm Hg, a minor amputation was seldom sufficient. Ankle and toe pressure indices gave no further information. PMID- 8349209 TI - Transcutaneous oxygen tension in the dysvascular foot with infection. AB - Eight adult insulin-requiring diabetics with peripheral vascular disease were admitted with foot infection and signs of systemic sepsis. Transcutaneous oxygen tension was measured at the foot and ankle prior to surgery. None of the values were sufficient to support wound healing. Four of the patients underwent open ray resection and four open midfoot amputation. After resolution of the local infections, transcutaneous oxygen tensions were repeated. Seven of the eight patients exhibited an appreciable increase in the value following decompression of the foot infection, sufficient to support wound healing. PMID- 8349210 TI - An anatomical study of the tarsal tunnel using low pressure compartmental infusion. AB - The anatomy of the tarsal tunnel is demonstrated using a low-pressure compartmental infusion technique. This is done by infusing colored radiopaque contrast material into three fresh cadaveric specimens. Thin section photography and computed tomography are then used to identify the boundaries and contents of the tarsal tunnel as it traverses the ankle, hindfoot, and midfoot. The tarsal tunnel is shown to communicate proximally with the deep posterior compartment of the leg and distally with the intermediate compartment of the forefoot. The relationships of the structures contained within the tarsal tunnel are shown in detail. PMID- 8349211 TI - Microvasculature of the tibialis anterior tendon. AB - Subcutaneous rupture of the tibialis anterior tendon is an uncommon condition for which the etiology is unclear. The existence of a hypovascular zone has been proposed as an etiology for rupture of the tibialis anterior tendon. To investigate this possibility, the microvascular anatomy of the tibialis anterior tendon was studied using a modified Spalteholz technique. The vascular supply to the tibialis anterior tendon arises from proximal and distal ventral vinculae. Muscular branches of the anterior tibial artery, proximally, and the medial tarsal arteries, distally, form an intratendinous, longitudinal, competent blood supply. The tendon also receives a rich vascular blood supply from the synovial sheath. The blood supply appears adequate throughout the course of the tibialis anterior tendon, and no hypovascular region was noted at the common site of rupture 1 to 3 cm proximal to its insertion. No relationship was noted between increasing age and alteration in blood supply. PMID- 8349212 TI - Management of giant cell tumor of the tarsal bones: a report of nine cases and a review of the literature. AB - Giant cell tumor of the tarsal bones is uncommon and therapeutic options are ill defined. We report on nine cases of giant cell tumors of the tarsal bones treated by excision of the complete bone in 6 cases, partial excision in 1 case, and curettage and bone grafting in two cases. There was no recurrence at an average 25.8-month follow-up. Function after calcanectomy was satisfactory. Excision of the talus may or may not be followed by arthrodesis, but arthrodesis is essential after excision of all the other tarsal bones except the calcaneus. We advocate aggressive surgical measures in these cases; amputation should be reserved for recurrences only. Satisfactory function may be expected after excision of tarsal bones. PMID- 8349213 TI - Reflex sympathetic dystrophy in an adolescent. AB - The clinical course of an adolescent with reflex sympathetic dystrophy of the foot is presented. The potential problems of establishing objective diagnostic criteria for reflex sympathetic dystrophy are related to the dynamic nature of the disorder. Serial radiographic studies, radionuclide scans, and quantitative densitometric measurements may be useful in combination; isolated cold stress testing and laser Doppler fluxmetry are useful in assessing thermoregulation and vasomotor instability. A regimen of amitriptyline and phenytoin plus physical therapy with stress loading was useful in this patient, but in many patients the course is progressive, leading to chronic pain and debilitation. PMID- 8349214 TI - The safety of the Esmarch tourniquet. AB - The use of an Esmarch bandage as a tourniquet in surgery has been criticized. Many authors claim that the pressures under the Esmarch are inconsistent and may be extremely high. We have seen few, if any, problems from the use of an Esmarch in surgery of the foot and ankle. The purpose of this study was to evaluate the pressures generated under the Esmarch tourniquet in a situation that mimics its clinical application, and to determine whether pressures of appropriate magnitude and consistency are obtained in order to recommend its continued use in surgery. Ten volunteers performed numerous applications of the Esmarch. The number of wraps and the width of the Esmarch bandage used were varied. The Esmarch was applied as it would be for a surgical case. Pressures directly beneath the Esmarch were recorded 8 cm proximal to the distal tip of the medial malleolus. Considering all volunteers and all pressures generated, a 3-in Esmarch applied with three wraps gave a mean pressure (+/- SD) of 225 +/- 46 mm Hg. A 3-in Esmarch applied with four wraps gave a mean pressure of 291 +/- 53 mm Hg. A 4-in Esmarch applied with three wraps gave a mean pressure of 233 +/- 35 mm Hg, and a 4-in Esmarch with four wraps gave a mean pressure of 284 +/- 42 mm Hg. The maximum pressures generated by any individual were as follows: 3-in three wraps, 321 mm Hg; 3-in four wraps, 413 mm Hg; 4-in three wraps, 328 mm Hg; and 4-in four wraps, 380 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349215 TI - Bilateral accessory soleus: a report on four patients with partial fasciectomy. AB - Four young adults (average age 24 years) presented with complaints of posterior ankle pain after running. Bilateral accessory soleus muscles were diagnosed using magnetic resonance imaging or CT scan. Symptoms were present an average of 3 years before diagnosis. Two patients had previous surgery (ankle arthroscopy, tarsal tunnel release, and leg compartment release) before diagnosis and treatment. Obliteration of Kager's triangle (posterior ankle fat pad) was present on six out of eight lateral ankle radiographs. Posteromedial prominence was present on four out of eight ankles. Operative exploration confirmed the presence of five muscles and fasciectomy was performed. Follow-up (17 to 29 months) showed good relief of symptoms in all patients and return to long-distance running for three patients. Dissection of 47 preserved cadavers revealed three accessory soleus muscles in the 94 extremities (two muscles were bilateral in one cadaver). PMID- 8349216 TI - Neurilemoma of the lateral plantar nerve producing tarsal tunnel syndrome: a case report. PMID- 8349217 TI - American Orthopaedic Foot and Ankle Society women's shoe survey. PMID- 8349218 TI - Forskolin and congeners. PMID- 8349219 TI - Steroidal oligoglycosides and polyhydroxysteroids from echinoderms. PMID- 8349220 TI - [Opening address of the elected president on the occasion of the 42d Congress of the German Society of Oro-, Maxillary- and Facial Surgery]. PMID- 8349221 TI - [Comparison of osteoplasty of the maxillary cleft with and without simultaneous osteotomy in patients with maxillary clefts]. PMID- 8349222 TI - [Special problems of Le-Fort-I osteotomy after bone repair of maxillary clefts]. PMID- 8349223 TI - [Dysgnathism operations in patients with previously operated lip-maxilla-palate clefts]. PMID- 8349224 TI - [Effect of bone repair after maxillary advancement surgery in cleft-induced forms of dysgnathism]. PMID- 8349225 TI - [Historical development and current status of osteoplasty of lip-jaw-palate clefts]. PMID- 8349226 TI - [Bone repair and secondary implant management of the maxillary cleft]. PMID- 8349227 TI - [Endosseous implants in maxillary bone repair]. PMID- 8349228 TI - [Assessment of cleft-induced maxillary segmental malocclusion by a "Dysgnathism Index" with further development of the 3D Dysgnathism Index based on 3D CT reconstruction]. PMID- 8349229 TI - [Has spongiosa bone repair produced good results?]. PMID- 8349230 TI - [Harvesting iliac crest bone spans in 172 maxillary cleft repairs: a retrospective study]. PMID- 8349231 TI - [Autogenous transplants for maxillary cleft repair: iliac crest or skull bone]. PMID- 8349232 TI - [Osteogenic value of the autologous skull bone transplant--comparative histologic and histomorphometric studies]. PMID- 8349233 TI - [Long-term results in adulthood after early childhood rib removal for primary bone repair of lip-maxillary-palatal clefts]. PMID- 8349234 TI - [Complications after removal of autologous bone transplants for repair of lip maxillary-palatal clefts]. PMID- 8349235 TI - [Spontaneous bone formation in the maxillary cleft--an alternative to bone repair?]. PMID- 8349236 TI - [Value of the laser in oro-maxillary-facial surgery]. PMID- 8349237 TI - [Photodynamic laser therapy and fluorescence diagnosis in squamous epithelial cancer of the oral cavity]. PMID- 8349238 TI - [Laser therapy of skin changes in the face and mouth mucosa]. PMID- 8349239 TI - [The CO2 laser in oro-maxillary-facial surgery]. PMID- 8349240 TI - [Osteotomy with the experimental laser system]. PMID- 8349241 TI - [Development, morphology and growth of alveolar stumps in maxillary clefts as the basic principles of osteoplasty]. PMID- 8349242 TI - [Principles of the laser technique for medicine]. PMID- 8349243 TI - [Opening address of the president on the occasion of the 42d Congress of the German Society of Oro-, Maxillary- and Facial Surgery in Munich]. PMID- 8349244 TI - [Effect of interdisciplinary cleft therapy on the nature and timing of maxillary cleft repair]. PMID- 8349245 TI - [Bone repair in unilateral cleft: when? With what?]. PMID- 8349246 TI - [A decade of maxillary cleft repair in an international comparison]. PMID- 8349247 TI - [15 years of surgical orthodontic experience with two types of maxillary cleft repair]. PMID- 8349248 TI - [Periodontal incision as surgical approach in maxillary cleft repair]. PMID- 8349249 TI - [Comparative results of tertiary repair with the Boyne flap or with the vestibular mucoperiosteal rotational flap]. PMID- 8349250 TI - [Bone selection in the area of the mandibular symphysis for secondary cleft repair]. PMID- 8349251 TI - [The discovery of individual physiognomy in modern art]. PMID- 8349252 TI - [Osteoplasty of lip-maxillary-palatal clefts with formed and compressed spongiosa]. PMID- 8349253 TI - [Long-term results of unilateral lip-maxillary-palatal clefts with primary osteoplasty]. PMID- 8349255 TI - [Evaluation of the growth of the facial skull after primary bone transplantation within the scope of bilateral maxilla-palate repair at the age of three years]. PMID- 8349254 TI - [Comparative long-term studies of growth behavior after lip-maxillary closure with and without primary osteoplasty]. PMID- 8349256 TI - [Clinical results of secondary osteoplasty of maxillary clefts in mixed dentition with lip-maxillary-palatal clefts]. PMID- 8349257 TI - [Roentgen findings after secondary and tertiary osteoplasty of lip-maxillary palatal clefts]. PMID- 8349258 TI - [Results of secondary maxillary cleft repair in patients with lip-maxillary palatal clefts with special reference to cleft-related small incisors]. PMID- 8349259 TI - [Maxillary bone repair as a portion of the total surgical concept in closure of lip-maxillary-palatal clefts]. PMID- 8349260 TI - [Bone repair of the maxillary cleft as a prerequisite for rhinoplasty]. PMID- 8349261 TI - [Resorption after bone repair of maxillary clefts--how to prevent it for the long term?]. PMID- 8349262 TI - [Transplant resorption in early and late bone repair with and without orthodontic closure of the space]. PMID- 8349263 TI - [Results of secondary bone repair in lip-maxillary-palatal clefts]. PMID- 8349264 TI - [Results of secondary maxilla-palate repair (4 years old) as residual defect osteoplasty]. PMID- 8349265 TI - [Growth of the facial skull in adult patients with unilateral lip-maxillary palatal clefts after early and late secondary bone repair of the maxillary cleft in comparison with normal probands of the same age]. PMID- 8349266 TI - [Bone repair of lip-maxillary-palatal cleft patients in adulthood]. PMID- 8349267 TI - [Indications for bone repair within the scope of revision osteotomy of the maxilla in patients with lip-maxillary-palatal clefts]. PMID- 8349268 TI - [Maxillary osteotomy and simultaneous osteoplasty in patients with lip-maxillary palatal clefts]. PMID- 8349269 TI - [Cervical intervertebral disk prolapse. Diagnosis, differential diagnosis and surgical therapy]. AB - Among the so-called cervical spine syndromes cervical disc prolapse represents a well defined disease entity which should be kept in mind considering treatment resistant painful neck and shoulder as well as neurological dysfunctions of this region. Differential therapy consists of conservative measures and especially a variety of surgical procedures for cervical disc syndromes. Under all circumstances decision for surgery has to take into consideration the individual psychological situation (e.g. expectations of the patient) and social factors (e.g. the patient's occupation). Therefore a close cooperation of the family doctor and the surgeon is required. The aim of this article is to point out the neurosurgical aspects as well as the point of view of the general practitioner at the same time. PMID- 8349270 TI - [Degree of familiarity with carcinoma in situ of the testis. A study of a representative selection of established urologists]. AB - METHOD: By a telephone poll conducted among 143 selected representative urologists in private practice throughout the west German Lander. BASIC REMARKS: Via a search for carcinoma in situ of the testicles (CIS, or testicular intra epithelial neoplasia, TIN), active early detection of testicular germ cell tumors is now possible. RESULTS: Among 143 urologists questioned, 62 claimed to be familiar with testicular CIS. However, only 52% were able correctly to answer one question as to its significance, and only 33% could correctly answer a question on the diagnosis of CIS. Only 28% of all those questioned were able to answer correctly 2 questions about CIS. Knowledge about CIS proved to be inversely correlated with the interval in years since obtaining a licence to practice as a specialist. CONCLUSION: The poll reveals that, at the present time, too few urologists are familiar with carcinoma in situ of the testicles, and the possibilities of active early detection of testicular tumors. PMID- 8349271 TI - [Obesity--how dangerous are the diets?]. PMID- 8349272 TI - [Weight reduction with alternative diets. Principles, philosophy, side effects, effectiveness. Part 1: Generally used reducing diets (as a comparison) and alternative diets A]. PMID- 8349273 TI - [Detection of occult blood in stool. Methodologic studies of the validity of this test principle with various test systems]. PMID- 8349274 TI - [The value of diuretics in monotherapy of hypertension]. AB - AIM: To represent the usefulness of thiazide diuretics as monotherapy of primary hypertension. MAIN POINTS: Moderate doses of thiazide diuretics can produce a reduction in blood pressure equal to that of beta blockers, calcium antagonists and ACE inhibitors, and achieve an equally high response rate. The advantages and disadvantages of the specific action profile of these diuretics are described. Discussions about the reduction in cardiovascular mortality is represented and practical conclusions drawn. The specific indications for monotherapy with thiazide diuretics include systolic, diastolic and isolated systolic hypertension in the elderly hypertensive, and hypertension in NYHA III and IV cardiac insufficiency. Suggestions for their use in practice are given. PMID- 8349275 TI - [Autotransfusion and concentrates or donor blood and fresh plasma? Legal pitfalls in the medical decision making paths (Part 1 of two)]. PMID- 8349276 TI - [Creutzfeldt-Jakob epidemic startles France. The cause is apparently a contaminated growth hormone--parallels to "bovine psychosis"]. PMID- 8349277 TI - Social recognition in ovariectomized and estradiol-treated female rats. AB - The behavioral phenomenon of social recognition has been extensively investigated in male rats. The present paper provides an insight into the recognition capacity of female rats studied throughout a sequence of hormonal states: after ovariectomy, after estradiol treatment, and several weeks after the termination of estradiol therapy. Investigatory behavior of the female oriented toward a juvenile male, 22-24 days old, was recorded during the 5-min exposure period. Reexposure was performed 30 or 120 min after the initial exposure. Reduction of the investigation time during reexposure to the same juvenile was used as a recognition criterion. It was found that: (a) Three weeks after ovariectomy, the investigation time of females was decreased upon reexposure to the same juvenile at 30 min. At this time point the investigation time of females reexposed to a novel juvenile was similar to that observed during the initial exposure. Both the same as well as a novel juvenile were thoroughly reinvestigated by females when 120 min elapsed between exposures. (b) Three weeks later, administration of estradiol dipropionate to ovariectomized animals (always 100 micrograms per animal at Days 10 and 3 before the testing) resulted in reduced investigation time during reexposure to the same juvenile at both 30 and 120 min. (c) Original time-response relations in the investigation appeared 6 weeks after the termination of estradiol treatment. These findings suggest that the presence of estradiol may be crucial for female recognition of males 120 min after a brief encounter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349278 TI - Effects of corticosterone on social behavior of male lizards. AB - Adrenal corticoid release is a major component of the stress response which can affect many body functions including behavior. The purpose of our studies was to examine the effects of corticosterone (B) on both the agonistic and courtship components of social behavior in male side-blotched lizards (Uta stansburiana). Of particular interest was the effect of B on plasma testosterone (T), a hormone known to influence aggression, and the importance of this action on the behavioral effects of B. Experiments included either castrated males, hormone (either B, T, or B + T)-implanted intact males, or sham males. Behavioral observations were recorded when these males were challenged with "immigrant" males; measurement of plasma steroids confirmed the efficacy of implants in elevating B and T. Castration, B implantation, and combined B and T implantation significantly reduced aggressive behavior to varying degrees, while T implants in intact animals had no effect. B implants significantly decreased plasma T levels (from 1.87 to 0.33 ng/ml), but this decrease was not essential for the inhibitory effect of B on aggression since B + T implantation also reduced aggression, even though plasma T was elevated above normal (67.6 ng/ml). In contrast, B implantation did not affect male courtship and copulatory behavior when males were presented with estrogenized females. These results suggest that the effect of B on social behavior is not through just a single route, that of decreasing plasma T, and that B can affect various intra- and intersexual behaviors differently. PMID- 8349279 TI - Effects of the nonsteroidal aromatase inhibitor, fadrozole, on the sexual behavior of male cynomolgus monkeys (Macaca fascicularis). AB - In many vertebrates, castration and hormone replacement and, more recently, the use of aromatase inhibitors, have shown that male sexual activity is mediated by the aromatization of testosterone (T) to estradiol (E2). In macaques, however, the systemic administration of E2, either alone or in combination with androgen, failed either to maintain or to restore the sexual activity of castrated males. The present study examines the effects of administering the nonsteroidal aromatase inhibitor, Fadrozole, either alone or combined with E2, to castrated, T treated male cynomolgus monkeys at a dose of 0.25 mg/kg/day. This dose inhibited by over 98% the conversion of T to E2 and the subsequent accumulation of the latter in hypothalamic cell nuclei. Castrated males bearing sc Silastic impants of T were each tested with an ovariectomized, E2-treated female partner before, during, and after being given minipumps delivering either Fadrozole or water (240 1-hr tests). Within 2 weeks, Fadrozole significantly reduced ejaculatory activity and male sexual motivation in the absence of changes in plasma T levels, which remained in the upper range for intact males. Additional estradiol treatment produced small but significant increases in ejaculations by three of the six males only, and measures of male sexual motivation remained unchanged (120 tests). The present results, which stand in contrast to our previous findings in macaques, support the view that aromatization of T is important for ejaculatory activity and sexual motivation in a male primate. They also suggest that exogenous E2, which reaches the brain from the systemic circulation, does not fully duplicate the behavioral effects of E2 produced locally in the brain by the aromatization of T. PMID- 8349280 TI - Effects of testosterone propionate upon the sexual and aggressive behavior of adult male marmosets (Callithrix jacchus) castrated as neonates. AB - In New World monkeys of the family Callitrichidae (marmosets and tamarins), females frequently give birth to dizygotic twins. Twins share a placental circulation throughout fetal development and are hemopoietic chimeras. Despite this, there is no masculinization (freemartinism) in females which develop next to a male co-twin. It has been suggested that the organizing effects of testicular androgen upon sexual differentiation of the brain occur mainly during early postnatal development in male callitrichids, rather than in utero. However, this report demonstrates activation of masculine copulatory behavior by testosterone propionate (TP) administered to adult male marmosets (N = 8) which were castrated in infancy (between Days 1-7). Effects of neonatal castration upon aggressive behavior during pair tests with females (high frequencies of aggression) and intact adult males (low frequencies of aggression) were also reversed by TP treatment in adulthood. While early postnatal androgen secretion plays an important role in behavioral development in marmosets, it appears that a substantial degree of neural sexual differentiation occurs in utero in males of this callitrichid species. PMID- 8349281 TI - Differential perinatal testosterone secretory capacity of wild house mice testes is related to aggressiveness in adulthood. AB - Testosterone secretory capacity of testicular Leydig cells was determined in fetal males of an aggressive and a nonaggressive genetic selection line of wild house mice. They were studied at Days 15-18 of gestation and on the first day after birth. A previously described morphometric method was used to quantify 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity, which may be considered to reflect circulating plasma testosterone in the fetus. The results of this study show that the testosterone secretory capacity of Leydig cells in the testis changes differentially during intrauterine development in males of the aggressive and nonaggressive selection lines. The peak secretory capacity is reached at Day 17 of gestation for the males of the aggressive selection line, while the peak for the nonaggressive males is reached on the first neonatal day. The larger anogenital distance observed in aggressive males suggests a higher prenatal testosterone level in these males. The importance of the difference in timing of the perinatal 3 beta-HSD peak top individual variation in adult aggressive behavior is discussed. PMID- 8349282 TI - Glucocorticoids facilitate mineralocorticoid-induced sodium intake in the rat. AB - We confirm and extend the finding that glucocorticoids facilitate mineralocorticoid-induced sodium intake in the rat. First, we report that subcutaneous injections of dexamethasone (DEX) increase deoxycorticosterone induced sodium intake. Second, we demonstrate that continuous intravenous infusions of either DEX or corticosterone or the TYPE II glucocorticoid receptor agonist RU28362 increases the sodium intake of aldosterone-treated rats. And third, we measured urine sodium loss and found that rats were in positive sodium balance while receiving aldosterone and the glucocorticoid agonist, suggesting that the increased intake of sodium was primary to renal sodium loss. When taken together with the fact that glucocorticoids can increase the TYPE I aldosterone preferring receptor population in the brain, the results suggests a role for the glucocorticoid hormones in the arousal of sodium appetite in the rat. PMID- 8349283 TI - Postpartum aggression in mice: the role of ovarian hormones. AB - The development of aggression during the immediate postpartum period was investigated in Rockland-Swiss albino female mice. Aggression was low immediately following delivery and increased with advancing lactation. The majority of females delivered during the dark cycle, however, whether females delivered or were tested during the light or dark cycle did not influence aggression. Females ovariectomized on Gestation Day 18 displayed aggression sooner than sham-operated controls. Estrogen treatment restored typical postpartum docility in prepartum ovariectomized females. Ovariectomy also increased the number of nursing bouts, but not total nursing time, when compared to sham-operated females. These findings suggest that peripartum estrogen stimulation, directly or through influencing nursing activity, prevents aggression in females immediately postpartum. PMID- 8349284 TI - Effects of progesterone and dihydrotestosterone on stimulation of androgen dependent sex behavior, accessory sex structures, and in vitro binding characteristics of cytosolic androgen receptors in male whiptail lizards (Cnemidophorus inornatus). AB - Progestins often act as potent antiandrogens in male birds and mammals. Experiments with lizards find that progestins can both inhibit (when given in high dosages) or stimulate (when given in low dosages) male-typical sex behavior in gonadectomized individuals. This study shows that in the little striped whiptail lizard exogenous progesterone (P) facilitates androgen-dependent sex behaviors in males yet fails to stimulate seasonal activation of androgen dependent accessory sex structures. Analysis of androgen receptors (AR) in brain and kidney cytosol of the little striped whiptail lizard reveals similarities with the AR of the mouse. The data indicate that despite the ability of P to mimic the actions of androgens in activating sex behaviors in males of this species, the characteristics of the AR are conserved with respect to other vertebrate species. PMID- 8349285 TI - Redundant use of luminance and flashing with shape and color as highlighting codes in symbolic displays. AB - Three visual search experiments evaluated the benefits and distracting effects of using luminance and flashing to highlight subclasses of symbols coded by shape and color. Each of three general shape/color classes (circular/blue, diamond/red, square/yellow) was divided into three subclasses by presenting the upper half, lower half, or entire symbol. Increasing the luminance of a subclass by a factor of two did not result in a significant improvement in search performance. Flashing a subclass at a rate of 3 Hz resulted in a significantly shorter mean search time (48% improvement). Increasing the luminance of one subclass (by a factor of five) while simultaneously flashing another significantly improved search times by 31% and 43% respectively, compared with nonhighlighted search conditions. In each experiment, the search times for nonhighlighted target subclasses were not affected by the presence of brighter and flashing targets. The failure of the initial experiment to find a significant performance improvement caused by increasing symbol luminance suggested that a larger luminance increase was necessary for this code to be effective. The overall results suggest that using luminance and flashing to highlight subclasses of color- and shape-coded symbols can reduce search times for these subclasses without producing a distraction effect by way of a concomitant increase in the search times for unhighlighted symbols. PMID- 8349286 TI - Disruption and maintenance of skilled visual search as a function of degree of consistency. AB - The present experiment was conducted to investigate the effects of varying degrees of task consistency on the performance and maintenance of skill in a semantic-category visual search task. Four groups of participants first received 6000 trials of consistent mapping (CM) training on two different categories. The participants then performed 4000 trials in which one of the previously trained categories remained 100% consistent, whereas the other previously trained category became either 100%, 67%, 50%, or 33% consistent. This second phase of the experiment allowed for the examination of disruption of the search skill as a function of degree of consistency. Subsequent to the degree of consistency manipulation, 100% consistency was restored and participants performed another 4200 CM trials. Results indicate that performance was disrupted by inconsistency and that disruption increased as consistency decreased. On the return of task consistency, performance improved rapidly to predisruption levels, though some performance disruption was evident. Theoretical and practical implications are discussed. PMID- 8349287 TI - Modeling strategic behavior in human-automation interaction: why an "aid" can (and should) go unused. AB - Task-offload aids (e.g., an autopilot, an "intelligent" assistant) can be selectively engaged by the human operator to dynamically delegate tasks to automation. Introducing such aids eliminates some task demands but creates new ones associated with programming, engaging, and disengaging the aiding device via an interface. The burdens associated with managing automation can sometimes outweigh the potential benefits of automation to improved system performance. Aid design parameters and features of the overall multitask context combine to determine whether or not a task-offload aid will effectively support the operator. A modeling and sensitivity analysis approach is presented that identifies effective strategies for human-automation interaction as a function of three task-context parameters and three aid design parameters. The analysis and modeling approaches provide resources for predicting how a well-adapted operator will use a given task-offload aid, and for specifying aid design features that ensure that automation will provide effective operator support in a multitask environment. PMID- 8349288 TI - Real-time expert systems interfaces, cognitive processes, and task performance: an empirical assessment. AB - In this experiment we investigated the effect of different real-time expert system interfaces on operators' cognitive processes and performance. The results supported the principle that a real-time expert system's interface should focus operators' attention on where it is required most. However following this principle resulted in unanticipated consequences. In particular, it led to inferior performance for less critical, yet important cases requiring operators' attention. For such cases operators performed better with an interface that let them select where they wanted to focus their attention. Having a rule generation capability improved performance with all interfaces but did so less than hypothesized. In all cases performance with different interfaces and a rule generation capability was explained by the effect of the interfaces on cognitive process measures. PMID- 8349289 TI - Repetitive motion disorders: the design of optimal rate-rest profiles. AB - Repetitive motion disorders of the upper extremities are the primary cause of lost time in hand-intensive industries. Typical remedies include the introduction of job aids and the redesign of the job. An alternative approach is considered here. Procedures are developed that can be used to determine the parameters of a job (e.g., the rate of work and the number and duration of the rest breaks) that minimize repetitive motion disorders and maximize productivity. It is shown that in theory the job parameters can be set so that one can achieve not only a decrease in repetitive motion disorders but also an increase in productivity. The application of the procedures to an actual manufacturing job requiring high repetitive, high-force hand motions is discussed in detail. PMID- 8349290 TI - Operation of controls on consumer products by physically impaired users. AB - The self-reliance of the physically impaired can be seriously jeopardized by their inability to operate everyday products, especially if both upper extremities are impaired. To determine the difficulties impaired users encounter in operating consumer product controls, on-site video recordings were made of subjects suffering from arthritis or a muscular disease. Subjects' force exertion was compared with that of a group of nonimpaired users. The resulting inventory allowed the analysis of the manipulation problems faced by impaired subjects and the development of design recommendations. In this study the force exerted by the subjects and that required to operate the controls were measured. A comparison of the results of these force measurements led to a number of conclusions. This study led to the following design recommendations: the amount of force required to operate controls should be kept as low as possible; the user should not be required to make two manipulations at the same time, such as simultaneously pushing and rotating a control device; pushing is preferable to rotating; and there should be a great degree of freedom to manipulate controls. PMID- 8349291 TI - Cognitive function at high altitude. AB - The effects of altitude on human performance and cognition were evaluated in a field study performed on Mount Denali in Alaska during the summer of 1990. Climbers performed a series of perceptual, cognitive, and sensory-motor tasks before, during, and after climbing the West Buttress route on Denali. Relative to a matched control group that performed the tasks at sea level, the climbers showed deficits of learning and retention in perceptual and memory tasks. Furthermore, climbers performed more slowly on most tasks than did the control group, suggesting long-term deficits that may be attributed to repeated forays to high altitudes. PMID- 8349292 TI - Headphone localization of speech. AB - Three-dimensional acoustic display systems have recently been developed that synthesize virtual sound sources over headphones based on filtering by head related transfer functions (HRTFs), the direction-dependent spectral changes caused primarily by the pinnae. In this study 11 inexperienced subjects judged the apparent spatial location of headphone-presented speech stimuli filtered with non-individualized HRTFs. About half of the subjects "pulled" their judgments toward either the median or the lateral-vertical planes, and estimates were almost always elevated. Individual differences were pronounced for the distance judgments; 15% to 46% of stimuli were heard inside the head, with the shortest estimates near the median plane. The results suggest that most listeners can obtain useful azimuth information from speech stimuli filtered by nonindividualized HRTFs. Measurements of localization error and reversal rates are comparable with a previous study that used broadband noise stimuli. PMID- 8349293 TI - Developmental maturation of the B-cell antigen receptor. PMID- 8349295 TI - Expression of protein tyrosine kinases in the Ig complex of anti-mu-sensitive and anti-mu-resistant B-cell lymphomas: role of the p55blk kinase in signaling growth arrest and apoptosis. AB - The src family of non-receptor protein tyrosine kinases (PTKs), including the blk, fyn, lyn and lck kinases, is expressed in B-lineage cells, may associate with the immunoglobulin receptor complex and, therefore, play a role in signal transduction via membrane IgM. To establish which of these PTKs is involved in growth inhibition of B-cell lymphomas by anti-mu, we examined the expression pattern and state of activation of these kinases in nine B-cell lymphomas. Tyrosine-phosphorylated p55blk was constitutively expressed in all growth inhibitable lymphomas; furthermore, anti-mu caused a relative increase of tyrosine phosphorylation in p55blk and a 2- to 3-fold increase in its kinase activity in these cells within minutes. In contrast, p55blk was not present in three of five anti-mu-resistant lymphomas and there was no detectable increase of blk activity in one of the resistant cell lines tested. Thus, we proposed that activatable blk kinase in the IgM complex is essential for the growth inhibitory effect of anti-mu. To test this hypothesis, CH31 lymphoma cells were treated with antisense oligos for the blk kinase and found to be resistant to anti-mu-mediated growth inhibition and subsequent apoptosis. These studies implicate the blk kinase as an integral part of the growth inhibitory pathway leading to arrest and apoptosis. Transfectants of blk gene constructs are being generated to further test this hypothesis. PMID- 8349294 TI - The mouse B-cell antigen receptor: definition and assembly of the core receptor of the five immunoglobulin isotypes. AB - We have shown that the core antigen receptor of all five isotypes is composed of immunoglobulin in association with a common heterodimeric alpha/beta sheath. The stoichiometry of the association is unknown although preliminary evidence points to it being an IgH2L2 [alpha/beta]2 association. Studies with chimaeric molecules indicate that much of the immunoglobulin-sheath interaction must occur through the carboxyterminal end of the molecule with particular importance being given to the linker-transmembrane region. The glycosylation of the alpha chain differs according to the isotype with which it is associated. There are two sites for N linked glycosylation on the alpha chain (Asn-30 and Asn-40); both sites are used. Mutation of Asn-30 alone decreases but does not abolish surface expression of the antigen receptor complex. Mutation of both sites prevents expression of the surface IgM[alpha/beta] complex but not of a surface IgD[alpha/beta] complex. Moreover, the pattern of alpha glycosylation is considerably affected by changes in the linker region between C mu 4 and the transmembrane, giving further support to the importance of this region in immunoglobulin-sheath interaction. Unlike IgM, IgD and IgG2b do not require alpha/beta for transport to the cell surface and can be expressed on the surface without either sheath or glycosyl phosphatidylinositol anchor. This finding may reflect that the IgD transmembrane region is significantly less hydrophobic than that of IgM; however, it should be noted that is not clear whether naked IgD exists in vivo. In fact, we have found that the alpha/beta sheath is necessary in order to facilitate efficient internalization and presentation of antigen by membrane immunoglobulin. The sheath presumably also plays a major role in potentiating transmembrane signalling. However, mutant receptors that do not associate with the alpha/beta sheath are nevertheless able to trigger phosphorylation of cellular proteins on tyrosine residues following cross-linking. Also, in addition to the alpha/beta sheath, other transmembrane proteins associate with the B-cell antigen receptor although they are not required in order to potentiate surface transport. It may be interaction with one of these other associated transmembrane proteins or, alternatively, interaction between the immunoglobulin cytoplasmic tail and, say, the cytoskeleton, that enables antigen receptors lacking the alpha/beta sheath to give rise to cellular signalling. PMID- 8349296 TI - Association of Src-family kinase Lyn with B-cell antigen receptor. AB - Antigen is thought to cross-link membrane-bound immunoglobulins (Igs) of B cells, causing proliferation and differentiation or the inhibition of growth. Compelling evidence suggests that protein-tyrosine phosphorylation is involved in signal transduction for cell proliferation and differentiation. Indeed cross-linking of membrane-bound IgM (mIgM) induced a rapid increase in tyrosine phosphorylation of at least 10 distinct proteins in B cells. The Src-family protein tyrosine kinase Lyn (p56lyn and p53lyn) is expressed preferentially in B cells. The Lyn protein and its kinase activity could be coimmunoprecipitated with both IgM and IgD from detergent lysates. Cross-linking of membrane-bound IgM with antibody induced down regulation of the Lyn protein. From these data we concluded that Lyn is physically associated with mIgs. Further evidence showed that cross-linking of mIgM induced rapid increase in the kinase activity of Lyn and association of Lyn with 85-kDa noncatalytic subunit of phosphatidylinositol 3-kinase. Thus, Lyn is likely to participate in B-cell antigen receptor-mediated signaling. As a novel signaling molecule downstream of Lyn, we identified src homology 3-containing, transcription factor-like molecule p75HS1. PMID- 8349297 TI - Antigen receptors on T and B lymphocytes: parallels in organization and function. PMID- 8349298 TI - Signal transduction pathways involved in B-cell induction. PMID- 8349299 TI - The B-cell antigen receptor: structure and function of primary, secondary, tertiary and quaternary components. PMID- 8349300 TI - Immunochemotherapy of human colon carcinoma xenografts in nude mice using combinations of idarubicin-monoclonal antibody conjugates. AB - Tumour cell heterogeneity is probably a principal cause of treatment failure and represents a formidable barrier for effective antibody-targeted chemotherapy. Idarubicin (Ida), a more potent and less cardiotoxic analogue of daunomycin, has been demonstrated to specifically target and eradicate homogeneous, cloned, murine tumour cell populations in vitro and in vivo when coupled to monoclonal antibodies (MoAb); however, the antitumour activity of Ida-MoAb conjugates against human tumour xenografts remains to be established. In this study, the value of cotargeting conjugates to different human tumour-associated antigens within a solid tumour has been assessed by comparing the effects of combinations of Ida-anti-colon carcinoma MoAb conjugates with any one Ida-anti-colon carcinoma MoAb conjugate used alone. Individual Ida-MoAb conjugates have previously been evaluated for their specific binding and cytotoxicity to one of two different human colon carcinoma xenografts (Colo 205 or LIM2210) in vitro, although their efficacy alone or in combination required assessment in vivo. Combinations of the most effective Ida-MoAb conjugates were demonstrated to enable a greater number of complete tumour regressions than the most efficacious Ida-MoAb conjugate administered alone in vivo; some combinations inhibited control tumour growth by up to 95%. This study suggests that Ida-MoAb conjugates can be effective against subcutaneous human tumours in nude mice, although it is unlikely that any single conjugate will eradicate all the tumour cells in a solid tumour, and the value of 'cocktails' of drug-MoAb conjugates against some xenografts (i.e. LIM2210) appears to be limited. PMID- 8349301 TI - Inhibition of burn-associated suppressor cell generation by glycyrrhizin through the induction of contrasuppressor T cells. AB - The inhibitory effect of glycyrrhizin (GR), an anti-inflammatory Chinese herbal drug extracted from licorice roots, on the generation of suppressor T cells in thermally injured mice (TI-mice) was investigated. The burn-associated suppressor T cell (BTs cell) activity was demonstrated in splenic mononuclear cells (SMNC) from mice 2 to 8 days after thermal injury when suppressor cell activity was assayed in a one-way mixed lymphocyte reaction. However, when TI-mice were treated with GR, SMNC harvested 6 days after thermal injury showed no suppressor cell activity. This activity of GR demonstrated a dose-response effect, with a dose of 10 mg/kg exhibiting peak levels of the activity. Since GR had no direct inactivating activities against BTs cells in vitro, the inhibitory effect of SMNC, derived from TI-mice treated with GR, on the activity of BTs cells was examined in the same mixed lymphocyte reaction system, and the results showed that the SMNC from GR-treated mice 6 days after thermal injury counteracted the activity of BTs cells. The type of cell responsible for this inhibition of BTs cell activities was a CD3+, L3T4+, Vicia villosa lectin-adherent T cell with the same phenotypic properties previously exhibited by contrasuppressor cells. These results suggest that GR may regulate the generation of BTs cells through the induction of contrasuppressor cells. Since there are many reports describing septic infections due to the appearance of BTs cells in postburn patients, it may be possible to apply GR or blood preparations containing contrasuppressor cell populations induced by GR in healthy volunteers into immunosuppressed burn patients to avoid infections. PMID- 8349302 TI - Killing by cytotoxic T cells and natural killer cells: multiple granule serine proteases as initiators of DNA fragmentation. AB - The vectorial secretion of the contents of highly specialized cytoplasmic granules is of pivotal importance to the killing by cytotoxic T cells and natural killer cells. The purification and biochemical characterization of some of the granule constituents, in particular the pore-forming protein perforin, had engendered the notion that the killing of cellular targets was largely an osmotic phenomenon analogous to the insult delivered by complement attack. However, the apparent absence of membrane perforation in various examples of lymphocyte mediated killing, and the observation that perforin alone could not account for apoptosis associated with programmed cell death, suggested that perforin activity represented, at best, only a part of the whole mechanism. More recently, the characterization of a large family of granule serine proteases (granzymes) has provided evidence that these molecules may collaborate in the killing process by inducing a 'suicide' pathway in target cells, resulting in DNA fragmentation. However, the serine proteases are inactive alone, their natural substrates have not been defined and they require access into the target cell cytoplasm via perforin-induced pores to exert their deleterious effects. Thus, we propose that the cytotoxic granule-mediated mechanism comprises at least two interdependent arms, perforin and serine proteases, that together are capable of inflicting cell death by osmotic shock and/or nuclear collapse. PMID- 8349303 TI - The maintenance of self-tolerance. AB - Two signal models for lymphocyte activation build on the Talmage/Burnet concept that receptor diversity is generated within the immune system by a random process, and that individual lymphocytes carry a single receptor on their surface that determines their specificity. Such models cannot use a concept of signal one anergy (or deletion) to explain the maintenance of self-tolerance in terms of the Bretscher/Cohn theory if they abandon the concept of associative recognition. PMID- 8349304 TI - Detection of mosaic protein mRNA in human astrocytes. AB - Mosaic proteins consist of a group of proteins that may be comprised of one or more types of a variety of different structural modules and have a diverse range of functions. We have examined primary human astrocyte cultures for the presence of three mosaic proteins, B2I and the complement proteins factor H and properdin. Using the polymerase chain reaction and an enhanced chemiluminescence detection technique, we were able to show that mRNA transcripts for each of these proteins are expressed in human astrocytes. PMID- 8349305 TI - Patterns of resistance to Candida albicans in inbred mouse strains. AB - Candida albicans infections were established in eight inbred strains of mice. Using established histological criteria, only two strains (AKR and CBA/CaH) were found to exhibit severe lesions. The remainder showed only mild tissue damage. Deaths occurred in three strains: CBA/CaH, A/J and DBA/2. The last two strains lack the important complement component C5. Colony counts in the brain varied widely between strains and showed no correlation with the extent or severity of tissue destruction. However, strains lacking C5 had a significantly greater fungal burden in the brain than C5-sufficient mice. The data are discussed in relation to concepts of susceptibility and resistance to C. albicans in experimental infections in mice. PMID- 8349306 TI - Origin and maintenance of germ-line V genes. AB - The distribution of nucleotide variability within the upstream of germ-line VH186.2-related variable genes was studied. The data in this report of work in progress indicate non-random selection for variability in the second antigen contact or complementarity-determining region (CDR2) for 12 such genes isolated using the polymerase chain reaction (PCR) technique from genomic C57BL/6 mouse liver DNA. The translated protein sequences of these and three additional previously published genes also display a pronounced Wu-Kabat peak of amino acid variability in CDR2. In the CDR1 and CDR2 regions of this set of related germ line genes, there are few [corrected] silent nucleotide changes, and most amino acid replacements (or non-synonymous changes) are non-conservative. In contrast, there is selection against amino acid replacement in the framework regions (FW), as indicated by the significant number of silent (or synonymous) mutational changes from the VH186.2 reference sequence. This is surprisingly similar to the Wu-Kabat variability patterns observed in somatically mutated immune response antibodies. These data could imply similar diversification mechanisms acting on B cell-expressed V genes in the soma (i.e. in a germinal centre) and in the germ line DNA of male and/or female germ cells. While always possible, we consider this unlikely. Similarly, we consider as unlikely an explanation based on a classical Darwinian model involving simple stepwise whole animal selection prior to reproduction for each VH and VL gene now phylogenetically stored in the V segment arrays of the genomic DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349307 TI - Manipulation of autoimmune diseases with T-suppressor cells: lessons from experimental SLE and EAE. PMID- 8349308 TI - Antibodies to carcinogen-DNA adducts in mice chronically exposed to polycyclic aromatic hydrocarbons. AB - Antibodies specific for polycyclic aromatic hydrocarbon (PAH)-DNA adducts have previously been reported in human sera. In this study, we examined the association between mixed PAH exposure and PAH-DNA adduct specific antibodies in BALB/c mice. Mice were treated either by i.p. injection or by intragastric (i.g.) intubation with a mixture of seven different PAHs [benzo(a)pyrene (BP), benz(a)anthracene (BA), fluoranthene (FA), dibenz(a,h)anthracene (DBA), 3-methyl cholanthrene (MC), chrysene (Ch), benzo(b)fluoranthene (BF)] at three doses (0, 15, 150 micrograms of each PAH) twice a week for 8 weeks. Sera were screened by direct ELISA for antibodies recognizing DNA modified by diolepoxides or epoxides of each PAH injected. In i.p. treated mice, the sera were slightly more reactive to DNAs modified with diolepoxides of BP, BA, or Ch or an epoxide of DBA than to unmodified DNA. In i.g. treated mice, the sera were more reactive to DNAs modified with diolepoxides of BA or BF than to unmodified DNA. For some PAHs, a dose-response effect was observed between sera reactivity to PAH metabolites and the dose of PAH administered. However, there was considerable variation in the immune responses among individual mice within each treatment group. When tested by competitive ELISA, none of the sera could discriminate between modified and unmodified DNA. This animal study suggests that an assessment of previous carcinogen exposure by measuring DNA adduct-specific antibodies requires further validation prior to its application to the human monitoring of carcinogen exposure. PMID- 8349309 TI - Production of a monoclonal antibody inhibiting the killer activity. AB - We established the hybridoma producing the monoclonal antibody (mAb) 3C3 by immunizing rats with mouse natural killer (NK)-like cells. The 3C3 mAb seemed to react mainly with T cells and T-lineage cell lines. The 3C3 antigen also seemed to be coincidentally expressed on a part of asialo GM1+ cells from nude mice, suggesting its expression on NK cells. Treatment of effector cells with 3C3 mAb markedly inhibited the killer activity against RL male-1 cells, but less so against YAC-1 cells, in vitro. It is suggested that the cell surface molecule defined by 3C3 mAb was closely associated with the killer activity of T cells and NK cells. PMID- 8349310 TI - The fate of protein antigen in earthworms: study in vivo. AB - Parenteral administration of antigen induces in the earthworms Lumbricus terrestris and Eisenia foetida the formation of antigen-binding protein. Labelled antigen was efficiently digested in the coelomic fluids of both species since the total amount of radioactivity in the coelomic fluids decreased. Antigen internalized in the free coelomocytes of both species was present in a TCA precipitable form, although the decline of total radioactivity was higher than in the coelomic fluid, indicating that the TCA-nonprecipitable fragments are rapidly released from coelomocytes into the coelomic fluid. Within the first 24 h after administration, labelled antigen was detected throughout all tissues except for the epidermis and cuticle, and after 4 days it was found in the chloragogenic tissue around the gut, dorsal vein and typhlosole. PMID- 8349311 TI - Inhibition of normal natural killer cytotoxicity by sera from hemophilic patients. AB - In this study we searched for circulating antibodies or other serum factors that could account for the natural killer (NK) defect observed in hemophiliacs (He) infected with the human immunodeficiency virus (HIV). We analyzed the effect of negative or positive sera for HIV from He on normal NK activity. We showed that sera from He interfered with normal NK cytotoxicity. The inhibitory activity was higher in HIV+ sera and increased as the HIV disease progressed. HIV- sera also inhibited NK function, although to a lesser extent than HIV+, and it was probably due to isoimmunization through replacement treatment with plasma-derived concentrates. For each individual, no direct correlation was found between NK inhibition (NK-INH) of sera and the NK activity of He peripheral blood mononuclear cells (PBMC). Furthermore, He serum was poorly inhibitory on autologous PBMC. Preincubation of allogenic effector or target cells with He sera revealed that the inhibitory effect was the result of the reaction with these cells. A positive correlation was found by comparing NK-INH of whole He sera with the serum levels of circulating immune complexes. When the NK-INH assay was performed using the same concentration of DEAE-purified IgG from N, HIV- or HIV+, we found that HIV+ AIDS IgG was more inhibitory than the others. PMID- 8349312 TI - Changes in the level of perforin and its transcript during effector and target cell interactions. AB - Perforin is a cytoplasmic granule protein expressed in cytotoxic lymphocytes, and is capable of lysing target cells. This protein is induced as cytotoxic T cells are activated, and the mRNA expression is modulated by various stimulators. These observations suggest possible changes in the level of perforin transcripts and protein when killer lymphocytes meet specific target cells leading to target cell death. To address this question, we examined three murine T-cell clones and primary human NK cells in perforin expression. When the cytotoxic lymphocytes were exposed to sensitive targets, perforin mRNA disappeared within 5 to 30 min and appeared within an hour thereafter. Among the murine T cell clones, L3 and OE4 showed two phases of mRNA decrease while human NK cells and the third murine T cell clone, AB.1, showed only one phase of mRNA loss during a 240 min period. The data indicate that when cytotoxic lymphocytes receive signals from a sensitive target, the cells rapidly degrade previously accumulated perforin mRNA and synthesize new transcripts. Interestingly, heat shock protein 70 mRNA was induced as the perforin mRNA levels recovered, while P55 Il-2 receptor mRNA was downregulated within 5 min after exposure to targets. The perforin protein level also rapidly decreased immediately after the interaction with the target, followed by a recovery, and then another decrease as seen in primary human NK cells, OE4 and L3 cells. However, in the AB.1 clone, no change in perforin content was detectable, despite the loss of perforin mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349313 TI - Anti-Mlsa-like effect of CBA/J anti DBA2 antibody in in vitro MLRs between Mls incompatible combinations. AB - Antisera from CBA/J (H-2k,Mlsa) mice hyperimmunised with DBA2 (H-2d,Mlsa) and/or AKR (H-2k,Mlsa) splenocytes, can block in vitro MLRs against Mlsa determinants. These two antisera are furthermore specifically cytotoxic against targets expressing H-2 components but not against Mlsa-bearing targets. In these experimental models the anti-Mlsa-like effects of CBA/J anti-DBA2 and CBA/J anti AKR antibodies seem to be associated with an autoreactive immune response in CBA/J mice elicited by DBA2 and AKR splenocytes, respectively. In this report we propose that anti-Mlsa antibodies can also be generated in a situation in which Mlsa is presented as 'altered self' in conjunction with allo-determinants. PMID- 8349314 TI - Increased expression of C1q receptors on neutrophils from inflammatory joint fluids. AB - C1q receptor (C1qR) expression was determined by immunofluorescence flow cytometry on neutrophils from paired peripheral blood and synovial fluid samples from 21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD). In both patient groups the levels of C1qR on circulating neutrophils were similar to that observed for normal control subjects, whereas on synovial fluid neutrophils significantly higher levels of receptor expression were observed. The mean percentage increases observed were: RA patients 47%, OAD patients 72%. C1q-bearing immune complexes were most prevalent in patients with RA, with the highest concentrations being found in synovial fluid samples. No correlation between immune complex levels and neutrophil C1qR expression was noted. Upregulation of C1qR expression is a feature of activated neutrophils from inflammatory joint fluids. PMID- 8349315 TI - A modified PABC immunoassay for the quantitation of DNA dependent RNA polymerase I: a procedure applicable to other proteins present in minute amounts and/or isoforms. AB - An indirect enzyme linked immunoassay (ELISA) has been developed to measure the amount of RNA polymerase I (E.C.2.7.7.6) in silkmoth tissue cell extracts. Subunit specific monoclonal antibodies (MABs) were immobilized on the solid substrate by a variation of the widely used Protein-Avidin-Biotin-Capture (PABC) technique. The use of the commercially available biotinylated anti-mouse antibody as a bridge to bind the monoclonal antibody eliminates the need for the biotinylation of the monoclonal antibody in the laboratory. The RNA polymerase in solution was captured by the monoclonal antibody and was measured by the successive binding of rabbit polyclonal antibody and alkaline phosphatase conjugated anti-rabbit antibody. This procedure is more reliable, reproducible and leads to greater sensitivity compared to the direct binding of the monoclonal antibody to the microtiter plate. RNA polymerase I captured by the antibodies from tissue extracts was measured at levels of 0.5 ng/well. This assay system can be utilized as a general procedure to quantitate the levels of proteins present at very low levels and that are found in different isoforms containing multiple and/or shared subunits. PMID- 8349316 TI - Distinct patterns of protective antibodies are generated against Borrelia burgdorferi in mice experimentally inoculated with high and low doses of antigen. AB - We have studied the development of clinical arthritis and the generation of protective antibodies in two normal, inbred strains of mice either infected by ticks or experimentally (subcutaneous) inoculated with increasing numbers of Borrelia burgdorferi organisms. AKR/N mice developed only mild and DBA/2 mice only marginal clinical arthritis irrespective of the route of infection or the numbers of spirochetes (10-10(8)) inoculated. In contrast, immunodeficient SCID mice developed severe chronic arthritis under similar conditions, but with a delayed onset at lower numbers of needle-inoculated spirochetes or after tick bite. AKR/N and DBA/2 mice inoculated with either 10(4) (and fewer) B. burgdorferi organisms or via experimentally infected ticks generated antibodies with specificities for a variety of B. burgdorferi antigens except those to the outer surface proteins A and B (OspA, OspB). In contrast, mice inoculated with more than 10(4) spirochetes (10(5)-10(8)) developed in addition antibodies to OspA and OspB. Most notably, all three types of immune sera taken from DBA/2 mice showed similar capacities to confer protection on SCID mice against subsequent challenge with viable B. burgdorferi organisms. The data not only demonstrate that the quality of humoral immune responses to B. burgdorferi in mice is determined by the antigenic load, they also indicate the existence of further protective antibodies with specificities distinct from OspA and OspB. PMID- 8349317 TI - Susceptibility to pristane-induced arthritis is altered with changes in bowel flora. AB - Pristane-induced arthritis (PIA) is unique among the animal arthritides in that a non-infectious, non-antigenic oil induces a chronic immune based arthritis with a prolonged delay between exposure to the inciting agent and development of the disease. Mice with pristane-induced arthritis have elevated T cell and humoral responses to the 65 kDa heat shock protein derived from Mycobacterium bovis (hsp65) and in common with several other models of autoimmune diseases the incidence of PIA is markedly suppressed by preimmunisation with hsp65 in Freund's incomplete adjuvant (Thompson et al. (1990) Eur. J. Immunol. 20, 2479). Recent studies have investigated how autoimmune reactions to heat shock proteins are involved in the development of arthritis. Arthritic CBA/Igb mice given pristane alone develop antibodies to both hsp65 and GroEl (bacterial 60 kDa heat shock proteins) and to hsp58 (the mammalian equivalent). Moreover, the splenic T cells of such mice proliferate vigorously in response to both bacterial and mammalian 60 kDa heat shock proteins. Remarkably, the anti-hsp65 antibody response in normal mice rises rapidly with age, directly correlating with the age related incidence of PIA. In addition, specific pathogen free mice (SPF) maintained in an isolator have negligible anti-hsp65 responses but these convert to positive responses if the animals are exposed to the open part of the animal facility (Thompson et al. (1992) Arthritis Rheum. 35, 139).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349318 TI - Flow regulation of vascular tone. Its sensitivity to changes in sodium and calcium. AB - Our hypothesis is that flow-through hydraulic drag or shear stresses the extracellular elements in the vascular wall. When the endothelium is intact, this results in the release of endothelium-derived relaxing factor and other substances, eg, prostanoids, from the endothelium. As in some reports, after inhibition of nitric oxide synthase, flow effects are still observed although diminished; the shear effect is extended mechanically to the subendothelial tissues. Shear causes conformational changes in the glycosaminoglycans by extending them from a randomly coiled aggregated state to a more elongated condition along the line of flow. This elongation and the consequent exposure of an increased number of cationic binding sites on the glycosaminoglycans lead to changes in sodium binding. The extent of the conformational change is influenced by the concentration of calcium, an ion that not only competes with sodium at specific binding sites but possibly cross-links the polysaccharide chains of the protein saccharide complex. These complex interactions might account for the cooperative, nonantagonistic interaction of sodium and calcium over the physiological concentration range. Sodium binding is influenced by changes in external sodium concentration, and this presumably accounts for the sodium sensitivity of the flow response. Although glycosaminoglycans are possibly the most studied in this regard, they are not the only candidates. Other extracellular proteins, either in conjunction with glycosaminoglycans or independently, might be involved. By mechanisms not yet identified, these changes are signaled to the cell. We have proposed that in part, at any rate, this may be related to the sodium concentration gradient. PMID- 8349319 TI - Possible genetic influence on the strength of human muscle nerve sympathetic activity at rest. AB - Large reproducible interindividual differences in the strength of human muscle nerve sympathetic activity have been demonstrated previously without satisfactory explanation. We undertook the present study to investigate whether a genetic influence may be a factor of importance. Microneurographic recordings of sympathetic impulse traffic were made in the peroneal nerve in nine pairs of monozygotic male twins and eight pairs of age-matched male subjects without family relationship. The strength of the sympathetic activity was quantitated as number of sympathetic bursts per 100 heart beats and bursts per minute. Group mean values of muscle sympathetic activity, heart rate, and blood pressure were similar in the two groups. Intrapair differences (mean +/- SEM) of sympathetic activity were 5.4 +/- 1.7 bursts per 100 heart beats (1.7 +/- 0.5 bursts per minute) for the twins and 19.4 +/- 3.2 bursts per 100 heart beats (11.8 +/- 2.5 bursts per minute) for the control subjects (P < .01 for both). The degree of reproducibility between twins is similar to that reported previously between repeated recordings in the same subject. The finding may indicate that the strength of sympathetic outflow to muscle is controlled genetically. If so, we speculate that this may contribute to the heritability of blood pressure in both normotensive and hypertensive subjects. PMID- 8349320 TI - Excitatory sympathetic reflex in NaCl-sensitive spontaneously hypertensive rats. AB - We have previously demonstrated blunted reflex responses of lumbar sympathetic nerve activity during volume expansion in NaCl-sensitive spontaneously hypertensive rats maintained on basal (1% NaCl) diets compared with NaCl resistant spontaneously hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats. The current study tested the hypothesis that chronic ingestion of a high (8%) NaCl diet further blunts cardiopulmonary reflex function in the NaCl sensitive spontaneously hypertensive rat. After 3 weeks of a 1% or 8% NaCl diet, male rats of all four strains were instrumented with femoral arterial and venous cannulas and lumbar nerve recording electrodes at 10 weeks of age. Two days later, conscious rats were infused with whole blood to expand blood volume. NaCl sensitive spontaneously hypertensive rats maintained on a 1% NaCl diet had blunted responses of nerve activity to acute volume expansion compared with control strains. NaCl-sensitive spontaneously hypertensive rats maintained on an 8% NaCl diet had increases in nerve activity responses to volume expansion. In a second experiment, the volume expansion protocol was repeated in anesthetized NaCl-sensitive spontaneously hypertensive rats that had been subjected to sinoaortic denervation after 3 weeks of a 1% or 8% NaCl diet. After sinoaortic denervation, an increase in nerve activity was again observed during volume expansion in animals fed the 8% NaCl diet. In animals fed the 1% NaCl diet, changes in nerve activity were variable. The excitatory response was significantly reduced after bilateral vagotomy. These studies suggest that blood pressure regulation in NaCl-sensitive spontaneously hypertensive rats is a complex interaction of excitatory and inhibitory sympathetic reflex systems that is altered by high dietary NaCl exposure. PMID- 8349322 TI - Enhancement of intracellular sodium by vasopressin in spontaneously hypertensive rats. AB - The arginine vasopressin-induced increase in intracellular sodium concentration was augmented in cultured rat vascular smooth muscle cells derived from 12-week old spontaneously hypertensive rats (SHR) compared with those from 12-week-old normotensive Wistar-Kyoto (WKY) rats. This difference was enhanced by treatment with a Na+,K(+)-ATPase inhibitor, ouabain. The calcium-free state did not affect the basal intracellular sodium concentration but completely blocked the arginine vasopressin-induced increase in intracellular sodium concentration in both cell groups. The arginine vasopressin-mobilized cytosolic free calcium was enhanced in SHR compared with WKY rats. This enhancement was diminished but not completely inhibited in the calcium-free state. Also, arginine vasopressin-produced intracellular alkalinization was augmented in SHR. Pretreatment of both cell groups with a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide, completely blocked arginine vasopressin-induced intracellular alkalinization and increased intracellular sodium concentration. Scatchard analysis showed that the V1 receptor number of either quiescent or proliferative cells of SHR was five to seven times greater than that of WKY rats, without any change in receptor affinity. These findings therefore indicate that the arginine vasopressin-induced increase in intracellular sodium concentration is augmented in vascular smooth muscle cells of SHR mediated through the enhancement of the mobilization of cytosolic free calcium and the activity of sodium-hydrogen exchange, which depends on an increase in V1 receptor number. PMID- 8349321 TI - Obesity-induced hypertension. Renal function and systemic hemodynamics. AB - This study examined the control of renal hemodynamics and tubular function, as well as systemic hemodynamics, during obesity-induced hypertension in chronically instrumented conscious dogs. Mean arterial pressure, cardiac output, and heart rate were monitored 24 hours a day using computerized methods, water and electrolyte balances were measured daily, and renal hemodynamics were measured each week during the control period and 5 weeks of a high-fat diet. After 7 to 10 days of control measurements, 0.5 to 0.9 kg of cooked beef fat was added to the regular diet, and sodium intake was maintained constant at 76 mmol/d throughout the study. After 5 weeks of the high-fat diet, body weight increased from 24.0 +/ 1.0 to 35.9 +/- 4.9 kg, mean arterial pressure increased from 83 +/- 5 to 100 +/ 4 mm Hg, cardiac output increased from 2.86 +/- 0.27 to 4.45 +/- 0.55 L/min, and heart rate rose from 68 +/- 5 to 107 +/- 9 beats per minute. Associated with the hypertension was an increase in cumulative sodium balance to 507 +/- 107 mmol after 35 days and a rise in sodium iothalamate space, an index of extracellular fluid volume, to 131 +/- 4% of control. Sodium retention was due to increased tubular reabsorption, because glomerular filtration rate and effective renal plasma flow increased throughout the 5 weeks of the high-fat diet, averaging 135 +/- 4% and 149 +/- 19% of control, respectively, during the fifth week of the high-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349323 TI - Rested-state contractions and rest potentiation in spontaneously hypertensive rats. AB - To gain further insight into the excitation-contraction coupling mechanisms in hypertrophy, we studied rested-state contractions, rest decay curves, and rest potentiation under different experimental conditions using papillary muscles of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar and Wistar-Kyoto (WKY) rats. Under constant stimulation at 1.1 Hz, contractility and relaxation were not significantly different in hypertensive when compared with normotensive animals. Rested-state contraction (the first beat after a rest interval of 15 minutes) increased to 159.2 +/- 23% and 123.5 +/- 7.5% of prerest values in Wistar and WKY rats, respectively, whereas in SHR it did not differ from prerest values (92.8 +/- 9.8%). Ryanodine, used to preferentially inhibit sarcoplasmic reticulum function, eliminated the differences in rested-state contractions observed between hypertensive and normotensive rats. Maximal rest potentiation (the first beat after a rest interval of 1 minute) was also significantly higher in Wistar and WKY rats than in SHR. These differences persisted at low extracellular Na+, when Ca2+ efflux via the Na(+)-Ca2+ exchanger was inhibited. Rest decay curves (the decay in contractility from maximal rest potentiation to rested-state contraction) showed a similar pattern in the three rat strains. The results suggest that the altered inotropic responses of the SHR arise from an alteration in calcium handling by the sarcoplasmic reticulum. Experiments on saponin-skinned trabeculae indicated that fractional calcium release induced by caffeine was significantly reduced in the SHR. We conclude that the altered inotropic response observed in SHR may reflect a diminished release of calcium from the sarcoplasmic reticulum. PMID- 8349324 TI - Potassium preserves endothelial function and enhances aortic compliance in Dahl rats. AB - It has recently been proposed that in rat models of genetic hypertension, supplemental dietary potassium preserves release of endothelium-derived relaxing factor independently of its capacity to either attenuate hypertension or increase plasma potassium. To test this hypothesis in Dahl salt-sensitive rats given sodium chloride (4%) for 3 weeks, we supplemented dietary potassium (2.1%) with either KCl (n = 16) or KHCO3 (n = 16). Compared with unsupplemented rats (n = 16), rats supplemented with either potassium salt had a lower mean arterial pressure and a greater release of endothelium-derived relaxing factor, as assessed from acetylcholine-induced relaxation of precontracted aortic rings. However, the maximum relaxation response to acetylcholine correlated inversely with blood pressure (r = -.82, P < .001), not only in the KCl (r = -.68, P < .002) and KHCO3 (r = -.77, P < .001) groups but also in unsupplemented rats (r = .86, P < .001). With potassium supplementation, plasma potassium concentrations measured between 4 and 6 PM did not increase, but those measured between 4 and 6 AM did increase (P < .05). In isolated ring segments, aortic compliance was greater in both the KCl and KHCO3 groups than in unsupplemented rats (0.015 and 0.017 vs 0.009 mm2/mm Hg) (P < .01). This greater compliance could not be related to differences in blood pressure, plasma potassium, or collagen or elastin content of the aortic wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349325 TI - Renal sodium excretion in sons of hypertensive parents. AB - The objective of this study was to evaluate whether renal excretion of sodium is impaired and whether tubular reabsorption of sodium is increased in normotensive white men with a familial predisposition to develop essential hypertension. We compared 11 normotensive sons of two hypertensive parents (SOHT) with 11 normotensive sons of two normotensive parents (SONT); renal sodium handling was assessed after 1 week of low-sodium diet (10 mmol/d) and after 1 week of high sodium diet (200 mmol/d). The SOHT were on average 5.5 years older than the SONT (46.9 +/- 5.2 [SD] vs 41.4 +/- 4.1, P = .012). On the sixth day of each diet, mean urinary sodium excretion did not differ between the two groups (12.9 +/- 6.3 vs 12.7 +/- 6.7 mmol/d on low-sodium diet, P = .930; 197 +/- 25 vs 200 +/- 27 mmol/d on high-sodium diet, P = .817). On the seventh day of each diet, baseline means for filtered load of sodium, absolute excretion of sodium, fractional excretion of sodium (an index of total tubular sodium reabsorption), and fractional excretion of lithium (an inverse index of proximal tubular sodium reabsorption) also did not differ between the groups. To assess renal sodium handling under non-steady-state conditions, we infused 2 L normal saline intravenously over a 2-hour period. The means for absolute excretion of sodium, fractional excretion of sodium, and fractional excretion of lithium increased from baseline, but the increases did not differ in magnitude between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349326 TI - Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects. AB - Blood pressure responses to 1 week of low-salt (20 mmol sodium/d) and high-salt (300 mmol sodium/d) intake were investigated in a single-blind randomized study in 163 white, nonobese normotensive subjects (65 women and 98 men; mean age, 38 +/- 1.2 years). The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake, as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counterregulator" when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet. Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible. Thirty subjects (18.4%) were classified as salt sensitive, 108 (66.3%) as salt resistant, and 25 (15.3%) as counterregulators. Multiple regression analysis revealed that age, body weight, and family history of hypertension contributed significantly to the change in blood pressure after the diets. Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension. An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension. Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects. The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects. Plasma norepinephrine concentrations were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349327 TI - Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects. AB - This study was designed to evaluate in healthy volunteers the renal hemodynamic and tubular effects of the orally active angiotensin II receptor antagonist losartan (DuP 753 or MK 954). Losartan or a placebo was administered to 23 subjects maintained on a high-sodium (200 mmol/d) or a low-sodium (50 mmol/d) diet in a randomized, double-blind, crossover study. The two 6-day diet periods were separated by a 5-day washout period. On day 6, the subjects were water loaded, and blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 6 hours after a single 100-mg oral dose of losartan (n = 16) or placebo (n = 7). Losartan induced no significant changes in blood pressure, glomerular filtration rate, or renal blood flow in these water-loaded subjects, whatever the sodium diet. In subjects on a low-salt diet, losartan markedly increased urinary sodium excretion from 115 +/- 9 to 207 +/- 21 mumol/min (P < .05). The fractional excretion of endogenous lithium was unchanged, suggesting no effect of losartan on the early proximal tubule in our experimental conditions. Losartan also increased urine flow rate (from 10.5 +/- 0.4 to 13.1 +/- 0.6 mL/min, P < .05); urinary potassium excretion (from 117 +/- 6.9 to 155 +/- 11 mumol/min); and the excretion of chloride, magnesium, calcium, and phosphate. In subjects on a high-salt diet, similar effects of losartan were observed, but the changes induced by the angiotensin II antagonist did not reach statistical significance. In addition, losartan demonstrated significant uricosuric properties with both sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349329 TI - Alcohol use and blood pressure in an unacculturated society. AB - Alcohol intake has been associated with higher blood pressure in acculturated populations but not in unacculturated societies. We performed a cross-sectional survey of a random community sample of 5023 male Yi rural farmers and 1656 Yi and 2173 Han men living in an urban setting. Average alcohol intake among drinkers was 36.4 g/d in Yi farmers, 56.5 g/d in Yi migrants, and 38.7 g/d in Han men. Age adjusted mean diastolic blood pressure was 66.9, 70.5, and 71.7 mm Hg, respectively. Diastolic blood pressure was higher at higher alcohol intakes in all three groups (all P < .001). After adjustment for age, body mass index, heart rate, smoking, and physical activity, the change (95% confidence interval) in diastolic blood pressure for each standard drink was 0.50 (0.38-0.62), 0.31 (0.18 0.43), and 0.24 (0.07-0.40) mm Hg for Yi farmers, Yi migrants, and Han men, respectively. The percentage of variance in diastolic blood pressure explained by alcohol intake was 5% for Yi farmers, 4% for Yi migrants, and 2% for Han men. In a random sample of 831 men, these associations were independent of urinary sodium, potassium, calcium, and magnesium and sodium-potassium ratio. In the Yi farmers, associations were less strong for systolic blood pressure and no longer significant after adjustment. Approximately 33% of hypertension could be attributed to daily alcohol use in the Yi groups compared with 9.5% in the Han people.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349328 TI - Elevated renovascular tone in young spontaneously hypertensive rats. Role of cytochrome P-450. AB - The present study examined the role of cytochrome P-450 metabolites of arachidonic acid in elevating renal vascular resistance in young spontaneously hypertensive rats (SHR). Differences in vascular tone were assessed in the preglomerular vasculature of 3- to 4-week-old prehypertensive SHR (n = 11) and normotensive Wistar-Kyoto (WKY, n = 10) and Wistar-Lewis (n = 10) rats. Pressure diameter relations to changes in renal perfusion pressure were compared using the juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution. At a pressure of 60 mm Hg, the basal diameters of the interlobular arteries and proximal and distal afferent arterioles of the SHR averaged 43 +/- 2, 17 +/- 0.3, and 11 +/- 0.4 microns, respectively. The diameters of the interlobular arteries and afferent arterioles were 9% to 14% smaller than those of corresponding vessels in WKY and Wistar-Lewis rats. Addition of P-450 inhibitors, ketoconazole (100 mumol/L) or 7-ethoxyresorufin (1 mumol/L), to the perfusate dilated the afferent arteriole of SHR by 7% to 12%, whereas it increased the diameter by only 0% to 6% in control rats and significantly reduced the differences in the pressure-diameter relation in the preglomerular vasculature of SHR and control rats. Inhibitors of P-450 eliminated the contractile response of afferent arterioles to increases in renal perfusion pressure in all three groups. Removal of calcium from the perfusate eliminated differences in the diameters of the preglomerular vasculature in SHR and normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349331 TI - Cardiac weight in hypertension induced by nitric oxide synthase blockade. AB - Wistar rats given a nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME), for 4 weeks develop time- and dose-dependent hypertension without cardiac hypertrophy. This initial study of the relation between left ventricular weight and L-NAME-induced hypertension has now been extended by giving 50 mg/kg per day L-NAME to Wistar rats (n = 30) for 8 weeks and comparing results with those from control rats (n = 10) and two-kidney, one clip rats (n = 14). Although L-NAME rats and two-kidney, one clip rats had increased systolic blood pressures during the last 3 weeks of the experiment (202 +/- 24 and 224 +/- 16 mm Hg, respectively), the ratio of left ventricular weight to body weight of L-NAME rats (2.12 +/- 0.32 mg/g) was not statistically different from that of control rats (1.93 +/- 0.13 mg/g), whereas that of two-kidney, one clip rats was increased (2.85 +/- 0.20 mg/g). The plasma renin activity of L-NAME rats was not significantly different from that of control rats. Two L-NAME rat subgroups were defined according to the presence of left ventricular hypertrophy (ratio of left ventricular weight to body weight > 2.19 mg/g, control mean +2 SD) (6 of 25) or its absence (19 of 25). Systolic blood pressure, plasma renin activity, and cardiac angiotensin converting enzyme activity of L-NAME rats with left ventricular hypertrophy were significantly higher than those of the subgroup without.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349330 TI - Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. AB - This study was conducted to compare the effects of omega 3 fatty acids, taken as fish or fish-oil supplements in the setting of a high- or low-fat dietary background, on blood pressure and heart rate in men with moderate cardiovascular risks. One hundred twenty men were randomly allocated to five high-fat (40% of daily energy) and two low-fat (30% of energy) groups to undertaken a 12-week dietary intervention period involving fish, fish oil, or a combination of these. Sodium intake was restricted to less than 90 mmol/d. The five high-fat groups were assigned to take either 6 or 12 fish-oil capsules daily, fish or a combination of fish oil and fish, or placebo capsules. The two low-fat groups took either fish or placebo capsules. Fish meals were devised to provide 1.3 g of eicosapentaenoic acid daily, equivalent to that contained in 6 fish-oil capsules. Subjects were instructed to eat a selection of fish that provided an average of 3.65 g/d (range, 3.2 to 4.1 g/d) of total omega 3 fatty acids. Subjects were seen at regular intervals during the baseline and dietary intervention periods for measurement of weight, blood pressure, heart rate, dietary compliance, urinary electrolyte excretion, platelet phospholipid fatty acids, blood glucose, and insulin concentration. There was a greater fall in both systolic and diastolic blood pressures in subjects allocated fish or fish oil, particularly in the low fat groups, compared with control subjects. However, there was no significant group effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349332 TI - Chlorothiazide. How the thiazides evolved as antihypertensive therapy. PMID- 8349333 TI - 1993 guidelines for the management of mild hypertension. Memorandum from a World Health Organization/International Society of Hypertension meeting. Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee. PMID- 8349334 TI - Paediatric trauma in the rural developing world: low cost measures to improve outcome. AB - We reviewed 181 injured children admitted to a rural African hospital from 1987 to 1990 to ascertain factors influencing survival and functional outcome. Burns were the most common (39 per cent), occurred in the youngest patients, and were due to domestic scalding in 54 per cent of cases. Of the patients, 65 per cent presented more than 24 h after injury and 81 per cent presented without any previous treatment. Major disability occurred in 14 per cent of survivors and was associated with Injury Severity Score (ISS), extremity injury, and delayed presentation. Mortality was associated with the ISS. The mean ISS was 6.3. An ISS of 20-25 was associated with 75 per cent mortality. Trauma caused 8 per cent of hospital deaths in the 5-19 years age group. To reduce the mortality and disability from paediatric trauma in the rural developing world, we recommend: (i) prevention strategies targeting domestic burns in younger children, (ii) increased attention to care of extremity injuries and burns, and (iii) increased use of non-medical health care providers in more remote areas. PMID- 8349336 TI - A simple and safe method for preservation of the injured spleen. AB - A total of 29 patients sustaining closed injuries of the spleen was evaluated after repair of the organ; 11 were children. The injuries were classified as grade II, 5; grade III, 22; and grade IV, 2. The spleens were repaired with figure-of-eight, 0 chromic catgut stitches placed at right-angles to the rupture using a liver needle. A thin layer of Surgicel was placed over the tear and each free side of the stitch. Haemorrhage from the spleen was controlled with this technique in 27 patients. Two patients with grade IV injury underwent ligation of the lower pole vessels and hemisplenectomy combined with patching and suture. Postoperative bleeding occurred in two patients with grade III injury, who then underwent splenectomy. The splenic function after splenorrhaphy was established to be perfect and there were no deaths. This modified technique of repair is a simple and safe method for preservation of the injured spleen. PMID- 8349335 TI - The paediatric cervical seat belt syndrome. AB - During a 9-year period, 541 children were admitted with injuries sustained as passengers in motor vehicle accidents. Of these, seven (1.3 per cent) had the cervical seat belt syndrome. Five children had fractures or fracture-subluxations of the proximal cervical spine, while two had injuries of the lower cervical spine. Head injuries occurred in four children, severe cervical spinal cord injuries in three, while a fracture of the larynx and recurrent laryngeal nerve palsies occurred in one child. All children were wearing three- or four-point restraints. In the former group, the neck injuries probably resulted from flexion of the neck over the poorly fitting sash of an adult-type lap-sash belt, while in the latter group, the injuries probably resulted from hyperflexion of the neck while the torso was securely restrained. One child died from a severe head injury and a complete cervical cord injury. Satisfactory spinal alignment and stability were achieved in the surviving children by non-operative treatment. However, only three children recovered completely from their injuries. Two require continuing care for cervical spinal cord damage and one has persistent tracheal stenosis and paralysis of the vocal cords. PMID- 8349337 TI - Hepatic trauma: experience of 110 cases. AB - A total of 110 patients with hepatic injuries was treated at a major urban trauma centre between June 1988 and December 1991. The mechanism of injury was blunt trauma in 86 patients (78 per cent). Non-operative treatment was given in six patients (5 per cent). Simple hepatorrhaphy, use of topical haemostatic agents or peritoneal drainage alone were performed in 79 (72 per cent) cases. Extensive hepatorrhaphy, hepatotomy with selective vascular ligation, resection and debridement or resection, perihepatic packing and major vascular ligation were undertaken, often in combination, in 25 (23 per cent) cases. Percutaneous arterial embolization was carried out in one case. The mortality rate was 18 per cent. The most frequent postoperative complications related to hepatic injury were intra-abdominal abscess (7 per cent) and coagulopathy (5 per cent); prolonged biliary leak (3 per cent), late haemorrhage (2 per cent) and hepatic necrosis (1 per cent) were also observed. PMID- 8349339 TI - The AO classification of long bone fractures: an early study of its use in clinical practice. AB - Over a period of 6 months, 543 long bone fractures were classified using the AO classification system. Factors important in determining the management of fractures occurring in three regions; hip, forearm and tibia, were identified. In hip fractures, we found that the anatomical configuration of the fracture, and therefore its classification, generally determined management. However, there were other factors that influenced the more specific form of surgical treatment used. In forearm fractures, the age of the patient was the most important factor determining treatment, while many factors, including consultant preference, determined the treatment of tibial fractures. While we found the system useful for audit purposes, we also found that it was unnecessarily complicated and often fell short of playing a useful role in the planning of management. PMID- 8349338 TI - Fractures of the scapula associated with traumatic paralysis: a pathomechanical indicator. AB - In this study, 25 cases of fracture of the scapula associated with traumatic paralysis were reviewed. The vast majority of the patients were young males, victims of high-speed traffic accidents. Of the vertebral injuries in this population, 76 per cent occurred in the thoracic region, 20 per cent in the lower cervical region and only one in the lumbar region. Complete paralysis was documented in 84 per cent of the patients. The characteristics of spinal column failure are determined by the anatomical configuration and the direction and energy of the impact. Important information about the latter can be extrapolated from careful analysis of the associated fractures. PMID- 8349340 TI - Valgus reduction of trochanteric fractures. AB - A total of 663 patients in whom a Dynamic Hip Screw was inserted for internal fixation of an intertrochanteric femoral fracture were studied prospectively to determine the optimum position of reduction. Results show that those fractures in which a valgus reduction was performed had a reduced incidence of fixation failure. For those fractures fixed in a varus position, 28 per cent of screws cut out from the femoral head. A valgus reduction is, therefore, to be recommended in preference to fixation in an anatomical position and a varus position must be avoided. PMID- 8349341 TI - Preoperative traction for hip fractures in the elderly: a clinical trial. AB - A consecutive series of 100 patients with femoral neck fractures were assessed by a mental test score on admission. The 67 scoring within the normal range were randomly assigned to skin traction or no traction between admission and operation. Using pain assessment scales and records of analgesic consumption, there was found to be little difference between the two groups. The conclusion was that skin traction offered no benefits in pain control for the patient and therefore should not be used routinely. PMID- 8349342 TI - Surgical treatment of acetabular posterior wall fractures. AB - This is an analysis of 52 fractures of the posterior wall of the acetabulum treated operatively and reviewed 2-15 years after injury. In 48 cases the fracture was associated with posterior dislocation of the hip, which was treated by closed reduction soon after the injury. In all but two of the cases there was a displaced single or comminuted fragment resulting in a large defect in the posterior acetabular wall; they were treated by open reduction and internal fixation to restore joint congruity and stability. In the remaining two cases, the fragment was small but trapped in the joint and was excised. A strict correlation was found between accurate reduction of the fracture and the clinical and radiological results, which were excellent or very good in 85 per cent and 87.5 per cent of the patients, respectively. Surgical and late complications were peroneal palsy in four patients, ectopic ossification restricting hip movement in two cases, aseptic necrosis in three, and osteoarthritis in another three cases. PMID- 8349343 TI - Operative treatment of displaced intra-articular glenoid fractures. AB - Operative treatment is indicated in displaced intra-articular glenoid fractures. We report the results of treating 14 such fractures with open reduction and stable internal fixation. With an average follow-up period of 30.5 months, all fractures healed. All shoulders are rated good according to Rowe's scoring system. Complication was minimal, apart from those which resulted from the concomitant chest injuries. We therefore conclude that the operative treatment for these fractures gives good and predictable results. Special attention should be paid to treat the complications resulting from the common association of chest injuries in these patients. PMID- 8349344 TI - Recurrent anterior glenohumeral joint dislocation and torsion of the humerus. AB - Two computerized axial tomographic sections, one taken just below the coracoid process and the other about 2.5 cm proximal to the interepicondylar line, were used to determine glenoid version and humeral torsion in 19 patients with recurrent anterior glenohumeral joint dislocation and in 23 controls. Analysis of interobserver variation revealed the method to be reliable. There was no difference in glenoid version between the two groups. However, humeral torsion was greater in patients (153 degrees) than in controls (144 degrees). It appears that increased humeral torsion may predispose to glenohumeral joint dislocation. PMID- 8349345 TI - Transfer of multiply-injured patients for neurosurgical opinion: a study of the adequacy of assessment and resuscitation. AB - A total of 21 consecutive referrals with multiple injuries (Injury Severity Score (ISS) 17-66), admitted into the Regional Neurosurgical Unit (RNSU) over a 1-year period from August 1989, was analysed to evaluate the risks associated with transfer of such patients from district general hospitals within the North West Thames Region. Injury assessment was deficient in nine cases. Four developed hypovolaemic shock during transfer, and in five resuscitation was inadequate. Four had minor head injuries and two had no head injury; of these cases, one died. There were four fatalities: the mean ISS in this group was 42, and in all cases deficiencies in resuscitation and assessment before transfer were identified. There were seven major missed injuries. All patients had musculoskeletal injuries and 16 required orthopaedic intervention within 6 h. Interhospital transfer of this group of patients carries significant risks, may be unnecessary, and may delay other surgical priorities. PMID- 8349346 TI - Selective conservatism in the management of penetrating abdominal bull-gore injuries. AB - In a retrospective analysis it was found that not all patients with penetrating bull-gore injuries of the abdomen need exploration by formal laparotomy. A policy of selective conservatism was followed in the management of 18 out of 20 patients with bull-gore injuries of the abdomen in whom peritoneal breach was established either on presentation or by digital exploration of the wound. Formal laparotomy was reserved for specific clinical indications. Out of the 18 cases, 14 (78 per cent) were successfully treated non-operatively with wound excision, simple closure of the wound, and careful repeated clinical evaluation. There was no mortality in this group. Four cases (22 per cent) were explored; three of these had indications for exploration on presentation and the fourth was explored 4 days after admission. The latter was the only death that occurred in the series; the cause of death was probably pulmonary embolism. Omental and/or bowel evisceration occurred in 11 out of 18 cases (61 per cent). However, this was not considered an indication for exploration and all 11 cases were treated by simple replacement of omentum or bowel into the abdominal cavity. Penetrating abdominal bull-gore injuries can be managed safely by a policy of selective conservatism, reserving formal laparotomy for specific clinical indications. PMID- 8349347 TI - Traumatic section of the median nerve: an unusual complication of Colles' fracture. PMID- 8349348 TI - Isolated cervical nerve root injury treated successfully by operative decompression. PMID- 8349349 TI - Simultaneous dislocations of the carpometacarpal and metacarpophalangeal joints of the thumb. PMID- 8349350 TI - Acinetobacter sp. osteomyelitis of the femur: a late sequel of unrecognized foreign body implantation. PMID- 8349351 TI - Fracture-dislocations of the spine that may spare the cord: an explanation. AB - The combination of severe fracture-dislocation of the spine with little or no damage to the spinal cord and its roots is rare. There is a characteristic pattern of bony injury that seems most likely to result from a combination of extension and longitudinal compression and may not endanger the neural tissue. The usual clinical features of severe injury of the spine may be lacking and the radiological interpretation is difficult. Although the reports suggest that these injuries are stable in deformity this may not always be so and the spine should be afforded the usual protection. PMID- 8349352 TI - Vascular injury by an intertrochanteric fracture fragment. PMID- 8349353 TI - Hidden dangers in apparently stable neck injuries. PMID- 8349354 TI - Balloon angioplasty catheters for endovascular tamponade after vascular trauma. PMID- 8349355 TI - Insertion of distal screws in interlocking intramedullary nails. PMID- 8349356 TI - A PC program to aid in the choice of the design matrix in multiple linear regression. AB - A PC program, DESIGN, which can be used to evaluate and compare alternative choices of the design matrix, X, in the general linear model y = X beta + epsilon is described, illustrated and made available to interested readers. Given X, the program (1) computes various measures of the 'stability' of X and X'X and (2) determines the precisions of estimates of the model parameters, beta, and of predicted values, y, at the given design points. Examples focusing on polynomial regression are given. PMID- 8349357 TI - Design and integration of a graphic interface for an expert system in oncology. AB - We describe a graphic user interface for an expert system in oncology. The main objectives of our work has been to facilitate the adaptation of the system to different clinical environments and potentiate the factors which more directly determine the acceptance of the system by its users. We present the design principles derived from the features of the clinical domain chosen and from the objectives of the system. These principles are reflected on the design of the screen and of the interaction and in the style of integration of the interface with the other components of the system. Underlying the application we describe is a graphic user interface management system which provides facilities for the fast prototyping and integration of interfaces. We describe here those features of this tool which make the practical application of the design principles we consider possible. PMID- 8349358 TI - An ACSL simulation of the respiratory system. AB - A simulation program for the respiratory system using ACSL (Advanced Continuous Simulation Language) is presented. The underlying model is based on the representation of ventilation as a phasic air movement in lungs during the respiratory cycle. The translation of the model with ACSL instructions is described in particular for continuous processes, such as respiratory gas exchanges, and discrete events, such as changes of respiratory phase. The advantages of using ACSL are discussed, and the utility of such a simulation program in both research and education is demonstrated. PMID- 8349359 TI - Interpretation of low kappa values. AB - The use of the kappa statistic is commonly accepted as a measure for interobserver variability. However, in some situations, the interpretation of kappa should be handled with care. In this study 21 obstetricians were asked to segment and classify 13 cardiotocographic recordings for the major fetal heart rate (FHR) patterns acceleration, baseline FHR level, deceleration and undefined segments. In two cases the kappa statistic showed a poor group agreement. These low kappa values, however, were mainly due to the high proportion of baseline segments indicated by the referees. This finding will be exemplified by a discussion of one of the cases. PMID- 8349360 TI - Modeling and simulating the evolution of resistance against antibiotics. AB - An epidemiological model is proposed for the spread of resistance against antibiotics in populations of bacterial pathogens. The host population, which is assumed to be constant, is divided into three compartments, viz. susceptible, hosts infected by an antibiotic-sensitive strain and hosts infected by a resistant strain. It is further assumed that susceptibles can be infected by either strain and that there is a possibility for cross-infection between hosts infected by the two strains. The rate of cross-infection can be enhanced by mutations or the transfer of plasmids conferring resistance. Equilibrium analysis was performed in order to determine which of the strain 'wins' the competition by the host. It is assumed that the eventual shift in the competition between the two strains is due to treatment by antibiotic (selective pressure). PMID- 8349361 TI - Heart failure. Unfinished business--a possible role for vasodilators. PMID- 8349362 TI - Balloon pulmonary valvoplasty: factors determining short- and long-term results. AB - Balloon pulmonary valvoplasty was performed in 139 patients (age 2-44 years) with pulmonary valve stenosis. The right ventricular peak systolic pressure decreased from 137.1 +/- 46.8 mmHg to 76 +/- 51.3 mmHg (P < 0.001) and the right ventricle to pulmonary artery peak systolic gradient decreased from 116.3 +/- 49 mmHg to 54.4 +/- 51.9 mmHg (p < 0.001). There was no significant change in systemic artery systolic pressure. The right ventricular peak systolic pressure to systemic artery systolic pressure ratio decreased from 1.13 +/- 0.41 to 0.63 +/- 0.42 (P < 0.001). Patients with incomplete immediate relief of obstruction (right ventricle to pulmonary artery peak systolic gradient > 35 mmHg) had higher pre dilatation right ventricular peak systolic pressure (161.1 +/- 45.3 mmHg vs. 93.9 +/- 38.8 mmHg, P < 0.001) and higher right ventricular peak systolic pressure to systemic artery systolic pressure ratio (1.31 +/- 0.42 vs 0.98 +/- 0.33, P < 0.001) pre-dilatation and were older (17.2 +/- 8.6 years vs. 12.8 +/- 9.7 years, P < 0.01). The residual right ventricle to pulmonary artery peak systolic gradients in the majority of patients were infundibular, which regressed at follow up even in patients who did not receive long-term oral beta blockers. Follow up catheterisation in 79 patients after 13 +/- 8.7 months showed a further fall in right ventricular peak systolic-pressure (P < 0.001) and right ventricle to-pulmonary artery peak systolic gradient (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349363 TI - Arterial duct morphology with reference to angioplasty and stenting. AB - We studied the angiographic morphology of the arterial duct in neonates with congenital heart diseases. We defined the variations in ducto-aortic angle, number of tortuosities and site of insertion into the aorta of the duct in five diagnostic groups: (i) patent arterial duct (unobstructed) (n = 27), (ii) coarctation of the aorta (n = 24), (iii) pulmonary stenosis (n = 23), (iv) pulmonary atresia (n = 19) with or without ventricular septal defect, (v) hypoplastic left heart syndrome (n = 3). In the patent arterial duct group the angles ranged from 80 to 139 degrees, mean 107 degrees; in the coarctation group, 76 to 136 degrees, mean 104 degrees; in the pulmonary stenosis group, -60 to 111 degrees, mean 43 degrees; in the pulmonary atresia group, -55 to 115 degrees, mean 25 degrees; in the hypoplastic left heart syndrome 92 to 105 degrees, mean 98 degrees. The angles for the pulmonary atresia and stenosis groups were significantly less than those for the coarctation and patent ductus groups (P < 0.001). A ventricular septal defect in patients with pulmonary atresia or pulmonary stenosis was significantly associated with a smaller angle, a more proximal and a more tortuous duct (P < 0.01). The varying morphology of the duct in neonates with congenital heart lesions, especially with right heart obstruction requires special attention when attempting catheter techniques of ductal stenting. In particular the angle of approach and the presence of tortuosities may increase the difficulty of endovacular stenting. PMID- 8349364 TI - Reliability and accuracy of measurement of transductal gradient by Doppler ultrasound. AB - Simultaneous continuous wave Doppler echocardiography, aortic and pulmonary artery pressure measurements were performed during cardiac catheterization in 46 patients with patent ductus arteriosus. Doppler-derived systolic, mean and diastolic transductal gradients correlated well with those measured by catheterization, respectively (r = 0.972, SEE = 6.8 mmHg; r = 0.965, SEE = 5.4 mmHg; r = 0.939, SEE = 6.2 mmHg), and there were clinically acceptable agreements between the two technical measurements. It is concluded that Doppler echocardiography is a reliable and accurate technique for noninvasive estimation of transductal gradients. PMID- 8349365 TI - Xamoterol in sinus node disease. AB - A pharmacological alternative to pace-maker implantation would be useful in some patients with sinoatrial disorder particularly since the single lead ventricular system usually fitted has disadvantages. Xamoterol, a cardioselective beta receptor partial agonist, has been shown to increase heart rate both in animals and in man. We, therefore, studied the effects of Xamoterol in patients with sinoatrial disease in a double blind, cross-over trial in 10 patients. Mean heart rates and number and duration of pauses were compared during the treatment phases of the trial with Holter monitoring. Mean heart rates were significantly increased between 01:00 h and 05:00 h (P < or = 0.02) and between 05:00 h and 09:00 h (P < or = 0.01) on Xamoterol. The number of sinus pauses were eliminated or reduced on Xamoterol in six patients, but there was an increased frequency in three patients. Xamoterol, therefore, does increase the heart rate and reduce the number of pauses in sinoatrial disorder, but only in some patients. PMID- 8349366 TI - Long-term efficacy of heparin exercise treatment for patients with chronic effort angina: evaluation by exercise Tl-201 myocardial scintigraphy. AB - To determine the effects of heparin exercise treatment on the coronary collateral flow reserve, exercise thallium-201 myocardial perfusion images were obtained with the same work-load before and late after heparin exercise treatment (17 +/- 2 months, mean +/- S.E.). In six patients with stable effort angina, to develop the collateral circulation, treadmill exercise was performed 20 times for 2-3 weeks with pretreatment with a single intravenous dose of heparin (5000 IU). The coronary collateral flow reserve was measured quantitatively as a severity score by analysis of exercise thallium-201 myocardial perfusion images. The severity score was decreased from 11,976 +/- 1722 to 5531 +/- 1967 (P < 0.05) long after heparin exercise treatment. The ST segment depression at the time of peak exercise was also decreased from 0.15 +/- 0.02 mV to 0.05 +/- 0.02 mV. In an additional five medically treated patients, these indexes remained unchanged during 18 +/- 3 months of follow-up period. These findings demonstrate that the coronary collateral flow reserve is significantly enhanced with heparin exercise treatment. These preliminary results lend support for heparin exercise treatment as one of the possible therapeutic modalities for treating patients with chronic stable effort angina. PMID- 8349367 TI - Peripartum versus idiopathic dilated cardiomyopathy in young women--a comparison of clinical, pathologic and prognostic features. AB - Clinicopathologic features of 13 women with peripartum cardiomyopathy were compared to 13 women aged 19 through 38 with idiopathic dilated cardiomyopathy. No presenting clinical or pathologic variable distinguished either group. However, the clinical course differed between the groups. Eleven of 13 patients with idiopathic dilated cardiomyopathy had a poor clinical outcome, defined as persistent heart failure or death. Patients in this group succumbed one year or more after disease onset. Five of 13 patients with peripartum cardiomyopathy had poor outcome, with death occurring 9 months or less after disease onset. The clinical course of peripartum cardiomyopathy appears distinct from that of idiopathic dilated cardiomyopathy in young women. PMID- 8349369 TI - Dissecting left subclavian artery aneurysm: an unusual presentation of coarctation of the aorta. AB - We report a patient with coarctation of the aorta who presented with acute dissection of a large left subclavian artery aneurysm. The patient underwent successful reconstructive surgery. PMID- 8349368 TI - Surgical removal of a lipoma of the heart. AB - In a 29-year-old woman echocardiography revealed a tumour originating from the anterior wall of the right ventricle. Noninvasive findings aroused suspicion of a lipoma. The tumour was removed under cardiopulmonary bypass, the resulting defect in the right ventricular wall being covered with a Goretex patch. Histological examination classified the tumour as a rhabdomyolipoma. PMID- 8349370 TI - Rapid progression of septal hypertrophy in an adult with hypertrophic cardiomyopathy and excimer laser-treated coronary artery disease. AB - We present the case of a 55-year-old man with rapid progression from asymmetrical septal hypertrophy to hypertrophic obstructive cardiomyopathy over a 1-year period leading to persistent anginal symptoms despite adequate treatment of his concomitant coronary artery disease. The potential mutagenic side effects of XeCl excimer laser-radiation that was used to remove the arteriosclerotic plaque from the left anterior descending coronary artery may have contributed to the sudden increase in septal thickness. PMID- 8349371 TI - Spectral Doppler flow profiles in neonates with obstructive lesions of the aortic arch. AB - The aim was to assess the value of continuous and pulsed wave Doppler ultrasound in the detection and differentiation of obstructive lesions of the aortic arch in neonates. In 31 neonates with proven arch obstruction (pre- or juxtaductal coarctation in 19 patients; postductal coarctation in five patients; interrupted aortic arch in four patients; aortic arch atresia in three patients), continuous wave Doppler interrogation of the descending aorta from the suprasternal notch revealed a high velocity jet (greater than 2.2 m/s) directed away from the transducer in 12 patients. Of these, four neonates had preductal coarctation, and five postductal coarctation. The remaining three patients had arch interruption or atresia. Image guided pulsed Doppler ultrasound recordings were obtained from the arch upstream from the obstruction, the descending aorta distal to the obstruction, and from the arterial duct. Patients with coarctation had a prominent diastolic flow directed away from the transducer in the arch upstream from the obstruction, representing a diastolic coarctation gradient, or diastolic steal either by the patent arterial duct or by collateral vessels. In contrast, patients with arch interruption or atresia had only a systolic flow signal in the proximal arch. Ductal flow was either bidirectional (preductal coarctation, arch interruption, arch atresia), continuous right to left flow from pulmonary artery to aorta (one case each of juxtaductal coarctation and arch atresia), or continuous left to right flow from aorta to pulmonary artery (postductal coarctation). In neonates wide patency of the duct often precludes the development of a large pressure drop across a coarctation. Conversely, a high velocity signal may be recorded from a patent but restrictive duct. In conjunction with imaging, pulsed Doppler velocity profiles from the arch and patent duct permit a meaningful interpretation of the haemodynamics of arch obstruction. PMID- 8349372 TI - Causes of syncope in children: a prospective study. AB - We prospectively evaluated 80 patients with syncope, between January 1991 and January 1992 to determine the causes of syncope in children. There were 35 male and 45 female patients, whose mean age was 10.5 years. A single syncopal attack had occurred in 30 patients and multiple attacks in 50. A cardiovascular cause was established in 22 (27.5%) patients and a noncardiovascular cause in 36 (45%). The cause remained unknown in 22 patients (27.5%). Vasovagal syncope was the leading cause of syncope in these patients with an incidence of 32.5%. These findings suggest that every patient who has even one syncopal attack should be promptly investigated since the underlying cause could be a life-threatening one. PMID- 8349373 TI - Primary cardiac sarcomas. A report of three cases and a review of the current literature. AB - Primary cardiac sarcomas are uncommon but they may mimic a wide range of common cardiac pathologies by their modes of presentation. Surgery is the mainstay of treatment for non-metastatic disease however, the incidence of tumour recurrence and late metastases is high. For metastatic disease, the response to chemotherapy and radiotherapy is poor and surgery should be reserved for palliation where appropriate. The emphasis should be on early diagnosis of primary cardiac sarcoma, enabling prompt and relevant management. PMID- 8349374 TI - Unilateral pulmonary artery agenesis: a rare cause of haemoptysis and pleuritic chest pain. AB - Haemoptysis and pleuritic chest pain are common presentations of cardiopulmonary disease. While a number of common disorders may explain these symptoms, occasionally unusual causes may emerge which should be considered in the differential diagnosis especially if pulmonary embolism is unlikely; so that inappropriate anticoagulation or thrombolytic therapy is avoided. We present a case of unilateral pulmonary artery agenesis, who presented with pleuritic chest pain and haemoptysis, and was initially treated as a case of pulmonary thromboembolism. PMID- 8349375 TI - Comparative study of gallopamil versus nifedipine in patients with ischemic heart disease. AB - In order to compare the anti-ischemic activity of gallopamil and nifedipine, a cross-over, double-blind, randomised trial was carried out in 30 male out patients with a history of stable exertional angina, proven coronary disease and a positive stress test (ST-segment depression > or = 1 mm). After a first 1-week wash-out period on placebo, the patients were randomised to gallopamil, 150 mg/day (50, 50 and 50) or nifedipine, 30 mg/day (10, 10 and 10) for 28 days. After a second 1-week wash-out period active treatments were crossed for another 28 days. At the end of each drug or placebo period, a physical examination, laboratory tests and a stress test were performed. Oral short-acting nitrates were permitted throughout the trial periods. Twenty-one patients finished all periods of the study. Both drugs reduced the maximum ST-segment depression during the exercise test: from 2.45 +/- 0.97 mm (placebo) to 1.95 +/- 0.82 mm (gallopamil, P < 0.05) and from 2.50 +/- 0.93 mm (placebo) to 1.75 +/- 0.84 mm (nifedipine, P < 0.05). Gallopamil but not nifedipine increased stress tolerance significantly: from 486 +/- 156 s (placebo) to 598 +/- 138 s (gallopamil, P < 0.05) and from 509 +/- 113 s (placebo) to 567 +/- 191 s (nifedipine, NS). No significant differences were found between drugs. Both calcium antagonists, gallopamil and nifedipine, showed similar efficacy in treating myocardial ischemia. PMID- 8349376 TI - Atenolol or nicardipine alone is as efficacious in stable angina as their combination: a double blind randomised trial. AB - BACKGROUND: Beta blockers and calcium antagonists are widely used in the management of angina pectoris in the belief that the combination is more efficacious than either drug alone. METHODS: This double blind randomised crossover placebo controlled study compares the effects of nicardipine, atenolol and their combination in 30 patients with chronic stable angina. Each treatment period lasted 6 weeks with dose titration after 3 weeks. Symptom limited treadmill exercise testing and radionuclide ventriculography at rest was carried out at the end of each treatment period. RESULTS: Total exercise duration and time to 1-mm ST-segment depression was significantly prolonged by nicardipine and atenolol when compared to placebo, the combination offered no additional benefit. Time to onset of angina was significantly prolonged by nicardipine and the combination but not by atenolol. Indices of left ventricular function were not significantly affected by any treatment other than an increase in left ventricular end diastolic volume on atenolol and the combination. CONCLUSIONS: Nicardipine and atenolol are equally effective in prolonging exercise duration and time to onset of ischemia in patients with chronic stable angina while the combination appeared to offer no additional benefit. Nicardipine prolonged the time to onset of angina significantly; again there was no further improvement with the combination. Neither drug appears to have an important effect on the parameters of diastolic function studied in patients with chronic stable angina. PMID- 8349377 TI - Effects of atenolol and diltiazem on exercise tolerance and ambulatory ischaemia. AB - Twenty-five normotensive patients with stable angina, angiographically documented coronary disease and normal left ventricular function were randomized to a crossover study comparing atenolol 100 mg x 1, sustained-release diltiazem 120 mg x 2, and their combination. A maximal symptom limited bicycle exercise test and a 24-h ambulatory electrocardiographic (ECG) monitoring were performed at the end of each treatment period. Exercise duration was increased equally in the different treatment groups. Time to onset of 1-mm ST-segment depression was longer with atenolol (P < 0.02) and combination therapy (P < 0.01) than with diltiazem. The maximal ST-segment depression was decreased with atenolol (P < 0.05) and combination therapy (P < 0.02), whereas, time to onset of angina was prolonged only with combination therapy (P < 0.03). The number of ischaemic episodes during ambulatory monitoring was lower with atenolol and combination therapy than with diltiazem (P < 0.01). The difference between atenolol and diltiazem was mainly due to lower ischaemic activity with atenolol between 06:00 h and 12:00 h (P < 0.05). Anginal frequency (P < 0.01) and nitroglycerin consumption (P < 0.05) were lower with combination therapy than with monotherapy. Thus, while comparable effects were achieved on clinical variables, atenolol appeared to be more effective than diltiazem, reducing myocardial ischaemia during exercise and ambulatory monitoring. With combination therapy, both clinical and electrocardiograph signs of ischaemia were improved. PMID- 8349378 TI - Coronary artery vasomotion in cardiac transplant patients with normal coronary angiograms. AB - In 18 consecutive transplant patients with normal coronary angiograms and without calcium blocker therapy, and in 20 controls, we measured the diameters of the left anterior descending artery using quantitative coronary angiography. Measurements were effected on the frames recorded 5 min or more after intravenous administration of 0.4 mg methylergometrine, and 2 min after subsequent 2 mg bolus intracoronary isosorbide dinitrate administration. The arterial vasodilatory capacity was defined as the ratio of the difference of the largest and smallest arterial diameters and the smallest diameter. We observed normal vasoconstriction of the different coronary arterial segments. Coronary arterial diameter decrease from basal state was about 8% and was more pronounced at the distal segments of the left anterior descending artery. There was no difference of vasodilatory capacity between transplant patients and controls for the proximal and middle portion of the left anterior descending artery, while the difference was highly significant for the distal portion. In eight patients, the decrease of the vasodilatory capacity was beyond the lower limit of the normal range of values. The significance of those quantitative angiographic abnormalities is still unproven. They could be due to early vasomotor capacity blunting after transplantation and to late structural alterations of distal coronary vessels in cardiac transplant patients. PMID- 8349379 TI - The effect of lorcainide on arrhythmias and survival in patients with acute myocardial infarction: an example of publication bias. AB - Ninety-five patients with suspected acute myocardial infarction were randomly allocated on admission to hospital on a double blind basis to treatment with lorcainide, a Class 1C anti-arrhythmic drug, or matching placebo. Treatment was continued for 6 weeks. Twenty-four-hour ECG tape recordings were made immediately on admission, on the sixth or seventh day after admission, and again just before the end of the treatment period. Lorcainide was shown to be an effective anti arrhythmic agent. The study was not designed to evaluate the effect of lorcainide on survival, but there were nine deaths among the 49 patients treated with lorcainide compared with only one in the patients given placebo. These findings are consistent with the results of the First and Second Cardiac Arrhythmia Suppression trials (CAST and CAST-II). This study was carried out in 1980 but was not published at the time: it now provides an interesting example of 'publication bias'. PMID- 8349380 TI - Electrocardiographic assessment of infarct size: comparison between QRS scoring of 12-lead electrocardiography and dynamic vectorcardiography. AB - Myocardial infarct size is one of the most important predictors of prognosis in patients suffering an acute myocardial infarction. It can be assessed by enzymatic and electrocardiographic methods. The present report compares dynamic vectorcardiographic monitoring, serial plasma enzyme activity measurements and QRS scoring according to Palmeri as techniques for infarct size estimation. We report the results from 74 patients with acute myocardial infarction, who participated in a randomized trial of treatment with alteplase. A good correlation was found between myocardial infarct size by estimation from enzymatic measurement and from dynamic vectorcardiography. Dynamic vectorcardiography correlated more closely with enzymatically estimated infarct size in patients with Q-wave infarction, regardless of infarct location, than did QRS scoring of the conventional 12-lead electrocardiogram. Furthermore, dynamic vectorcardiography requires no time-consuming analysis and can be used for on line monitoring of patients with ongoing infarction to estimate the size of an acute infarction while it is developing. PMID- 8349381 TI - Cardiomyopathy secondary to sinus tachycardia. AB - We describe a case of cardiomyopathy resulting from a tachycardia of high-right atrial origin indistinguishable from sinus tachycardia. The symptoms and angiographic appearances improved dramatically with beta blockade. PMID- 8349382 TI - Atrial permanent pacing for sinus node dysfunction with absent right superior vena cava. AB - In patients with sinus node dysfunction and normal atrioventricular conduction, single chamber atrial pacing (AAI or AAIR mode) represents the most physiological treatment. Sinus node dysfunction is recognised in association with an absent right superior vena cava, and we present a case in which complete resolution of symptoms was achieved with endocardial atrial permanent pacing. PMID- 8349383 TI - Anomalous coronary arteries. PMID- 8349384 TI - Percutaneous transluminal coronary angioplasty or coronary by-pass surgery in the management of chronic angina pectoris. AB - The treatment modalities for patients with chronic stable angina have expanded since the introduction of percutaneous revascularization procedures such as percutaneous transluminal coronary angioplasty. In selected patients, these percutaneous procedures provide an excellent alternative to surgical revascularization; in other patients, percutaneous transluminal coronary angioplasty is an excellent alternative to medical therapy. Selection of the optimal therapy depends on the specific coronary anatomy, left ventricular function, clinical setting, and the need for complete revascularization. Also, the availability of bailout devices, such as stents for the dilatation procedure, needs to be considered in higher risk patients or higher risk lesions. Currently, randomized trials that are being completed will allow comparison of surgical versus angioplasty approaches and will improve our ability to tailor therapy for specific subsets of patients. PMID- 8349385 TI - The anti-arrhythmic effect of D-Ala 2, Leu 5, Arg 6-enkephalin and its possible mechanism. AB - We studied antiarrhythmic action of D-Ala 2, Leu 5, Arg 6-enkephalin (dalargin) in experiments on male rats. Dalargin is reported to prevent heart rhythm disturbance and heart electrical stability decrease in experimental coronary occlusion, postinfarction, cardiosclerosis and emotional stress. Dalargin prevents acute myocardial ischaemia-induced increase of cAMP content in blood serum and cardiac muscle, as an indirect feature of its antiadrenergic activity. D-Ala 2, Leu 5, Arg 6-enkephalin leads to a decrease of cAMP content in myocardium and blood plasma, which presumably indicates a decrease of sympathetic tone. The data strongly suggest that cGMP content increase and somatostatin level decrease in cardiac muscle play a significant role in antiarrhythmic action of dalargin. PMID- 8349386 TI - Conceptions of alcoholism among Koreans and Americans. AB - Ethnographic research has occasionally reported the presence (or absence) of the disease concept of alcoholism in non-Western cultures. But the problem of differences in the nature of the concept of alcoholism between cultures in which it exists has not been seriously investigated. This study contrasts beliefs about alcoholism among samples of Koreans and Americans at a university in the United States. The findings suggest that the concept of alcoholism is present in both cultures, but Koreans tend to restrict their disease to the physiological consequences of long-term alcohol use, while Americans accept a definition which is couched largely in social and behavioral terms. It thus appears that, in contrast to America, alcohol consumption in Korea is relatively high, but alcoholism is rare. The implications of these findings for drinking behaviors, and the diagnosis and treatment of alcoholism, are discussed. PMID- 8349387 TI - Population estimates of intravenous drug users and HIV infection in Los Angeles County. AB - This study applies multiple-capture models to drug treatment data and the synthetic estimation method to arrestee data to provide estimates of the number of IVDUs in Los Angeles County in 1989. Based on the 5% HIV-prevalence rate currently found in IVDUs in Los Angeles, it is estimated that there could be as many as 9,500 HIV-infected IVDUs. The estimates of IVDUs are generally higher than those obtained by back-calculation methods which often undercount IVDU related AIDS cases and do not consider deaths for causes other than HIV infection. PMID- 8349388 TI - The characteristics of recovering chemically-dependent Manitoba nurses. AB - Information about potential risk factors and characteristics of chemically dependent nurses is imperative to the development of primary and secondary prevention strategies. However, little is known about nurses who become dependent on chemicals, especially outside of the United States. In Canada, there is a dearth of studies. The purpose of this descriptive replication study is to provide information about the characteristics of chemically-dependent nurses in Manitoba, Canada, and to determine whether these characteristics are unique to one Canadian province or resemble an international profile. The study utilized an anonymous mailed survey to collect quantitative data from 22 recovering nurses. The majority of characteristics of the Manitoba nurses were similar to those found in American studies, thus adding further support to patterns emerging in the data base. PMID- 8349389 TI - Worksite smoking control, discouragement, and cessation. AB - Smoking control, discouragement, and cessation were investigated at three comparable chemical plants. One plant was randomly assigned to smoking cessation only while the other two plants were assigned to a comprehensive program of smoking control, discouragement, and cessation. Three weeks later, smoking cessation was provided at all three sites. Results are consistent with a previous investigation of the comprehensive program carried out at two oil refineries. Not only was there a greater rate of participation in the smoking cessation program with the comprehensive program, 4 months after completion of smoking cessation treatment revealed significant changes on all outcome variables in the expected direction and suggest the superiority of a comprehensive program of smoking control, discouragement, and cessation over cessation alone. PMID- 8349390 TI - Sexual risk behavior among injection drug-using human immunodeficiency virus positive clients. AB - This study examined sexual risk behavior of 154 seropositive Hispanic injection drug-using clients who were a subsample of a larger study. The results revealed that while nearly 71% followed safe sex practices at a 6-month follow-up, the other 29% were following risky sexual behaviors. Among males who were 25 years of age or younger, slightly over 58% were practicing unsafe sex. Among females, those in the 31-35 age group were all following risky sexual behaviors. Generally, those who lived with their sexual partners, females, and younger clients tended to follow risky sexual behaviors. These findings are very significant in the light of the heterosexual transmission of Human Immunodeficiency Virus (HIV). Educational and case management programs are needed to provide such clients with an understanding of the possibility of HIV transmission to their sexual partners and to their children in case of pregnancies. PMID- 8349391 TI - Which lesson components mediate refusal assertion skill improvement in school based adolescent tobacco use prevention? AB - Any of three components of current school-based refusal assertion training might mediate improvement of seventh grade students' ability to refuse tobacco use offers: 1) teaching students knowledge of ways to say "no," 2) engaging students in the practice of refusal assertion, or 3) motivating students to perform refusal assertion in a socially skilled way. A 3-condition true field experimental "component study" of the differential effects of these three components yielded improvement in role-played behavioral skill to refuse tobacco offers that was evident in both the Knowledge and Practice conditions but not in the Motivation condition. In these same two conditions, skills training led to a significant decrease in students' intention to use smokeless tobacco in the future but not cigarettes. A focus on engaging students in Knowledge and Practice components of refusal assertion training appears warranted. PMID- 8349392 TI - Reasons given by college students for drinking: a discriminant analysis investigation. AB - Based on self-reported levels of alcohol consumption, 473 college students (295 female and 178 male) were placed into at-risk or not-at-risk groups. Using reasons given for drinking as the independent variables, discriminant analysis procedures were conducted separately on the males and females to determine if a function could be found which would discriminate between the groups. For the female group, 11 of 22 reasons defined a discriminant function which accounted for 36% of the variance between the groups (p < .001). This function was also able to correctly classify 71% of the holdout sample. For the males, five of the 22 reasons defined a discriminant function which accounted for 36% of the variance between the groups (p < .001). This function was able to correctly classify 69% of the holdout sample. PMID- 8349393 TI - Affect and outcome in short-term group therapy for loss. AB - Affect and work variables were monitored for 12 of 16 groups involved in a controlled outcome study of psychoanalytically oriented short-term group therapy. Groups were conducted by experienced therapists for outpatients who experienced difficulties adapting to personal losses through death, separation, or both. Postsessional ratings of positive and negative affect were provided by individual patients, therapists, and other patients. Psychodynamic work was rated independently using a content analysis system. Patients who had experienced separation were more inhibited in their affective expression. Rating sources agreed that positive affect increased over time. Direct relationships were found between positive affect and favorable outcome. Concerning negative affect, the strongest predictors of favorable outcome involved the interaction of affect and work. Implications of these findings are discussed in terms of the cathartic hypothesis. PMID- 8349395 TI - The impact of unstructured games of fantasy and role playing on an inpatient unit for adolescents. AB - Games of fantasy and role playing such as Dungeons and Dragons (1983) have become increasingly popular among adolescents and young adults. This article reviews the negative impact of such games on an adolescent inpatient treatment setting. The unrestricted play of such games contributed to the disruption of a treatment setting, resistances to treatment, reinforcement of character pathology, disruption of individual treatments, and to the normalization of violence. When such games begin to be played on a psychiatric inpatient unit or are prominent in discussions of individual patients, treaters should examine them in the context of their potential to reinforce and foster resistance and maladaptive patterns of relating to the environment. Treaters are also encouraged to attempt to understand the meaning and risks of such games in the context of an individual patient's psychiatric difficulties and of group dynamics, both within the patient group and between patients and treaters. PMID- 8349394 TI - Group psychotherapy with bipolar patients: a review and synthesis. AB - Contrary to traditional thinking, a review of the recent literature has suggested that bipolar patients can be treated in homogeneous therapy groups in conjunction with concomitant lithium management. Important psychodynamic and interpersonal features are reviewed that have received empirical support and have enhanced our understanding of these patients. Goals for bipolar groups include educating patients on the nature of the disease, helping them learn ways of coping with its symptoms, and encouraging them to discuss relevant psychodynamic and interpersonal issues. To achieve these goals, therapists have used techniques involving education, support, and facilitation of group discussions. Further clinical and empirical work needs to be done to evaluate the effectiveness and process of these bipolar groups, particularly in the inpatient setting. PMID- 8349396 TI - Varieties of learning in an experiential group. AB - Variously described as enhancing sentence, supporting professional identity, providing insight and introducing the resident to covert group processes, the experiential group has been a part of residency education for over 25 years. This article specifically focuses on and identifies the potential areas for learning about group process in such an experience. These areas are organized around the contribution of individual psychological, social-psychological, and group-as-a whole issues in the group. Actualization of the learning depends on the psychological state and level of emotional preparedness of the individual member, the consultant's orientation and style, the composition and development of the group, and its relationship to the organization in which it takes place. An example is provided to highlight the areas of potential learning, and there is a discussion of some applications to the patient role and the practice of group psychotherapy. PMID- 8349397 TI - Control and power in supervision. AB - This article explores the dynamics of the supervisory process focusing on the factors effecting the balance of power between the supervisor and supervise. The assignment of inherent roles, issues of transference, countertransference, and the parallel process with all the risks involved for both parties are reviewed. Recent developments in the shifting supervisory equilibrium are analyzed and specific suggestions are offered to avoid the common pitfalls present in many contemporary supervisor situations. PMID- 8349398 TI - Employment barriers and work motivation for Navajo rehabilitation clients. AB - The Navajo nation provides vocational rehabilitation (VR) services to Navajo clients residing on and off the Navajo reservation. To evaluate motivation among disabled Navajo workers participating in VR programs, this study investigated the sociocultural meanings of work and its importance in the self-identity of contemporary Navajo workers and clients who apply for these services. Selected sociocultural variables that focused on cultural identity and perceptions as well as attitudes towards work were included as part of an assessment designed to predict motivation for employment success. The results of this study suggest that VR counsellors who work with Native American clients should recognize sociocultural history and the cultural perceptions of work as important factors in the rehabilitation and vocational planning process. PMID- 8349400 TI - Community-based rehabilitation cadres: their motivation for volunteerism. AB - Volunteer workers, or cadres, are critical to the successful implementation of community-based rehabilitation (CBR) programmes. To date, relatively little research has examined the importance of motivation in health volunteers in general, and especially CBR workers. This paper reports the major findings of a field study in rural Indonesia. A multimethod design within a broad qualitative research framework which focused on the personal experiences of CBR volunteers was utilized. Descriptive data were obtained from written questionnaires, focus groups and key informant interviews. Research findings indicated that volunteer cadres perform considerable duties and face numerous difficulties in the course of their CBR activities. Incentives also play an important role in determining the motivation and ultimate performance of volunteer cadres. Developing an understanding of what it is like to be a volunteer CBR cadre has important implications for rehabilitationists interested in developing and sustaining CBR programmes and is clearly critical to any evaluation of CBR. PMID- 8349399 TI - Perceiving oneself as 'disabled' or as having a 'disabling condition': a discriminant function analysis. AB - Using discriminant function analysis, information obtained in telephone interviews with a national, random sample of 1000 Americans with self-ascribed disabling conditions was analysed to cast light on differences between individuals who did and did not consider themselves 'disabled'. Maximum separation between the two groups was attained by an equation of six descriptors. In the order of their importance they were (1) the belief that others who knew them well considered them disabled, (2) self-rated severity of disability, (3) identification with others with disabilities, (4) gender, (5) perceived extent of limitations, and (6) needing equipment to walk. Somewhat different equations were generated for sampled men and women. An appreciation of these results in terms of a person's fit with his or her environment is offered. PMID- 8349401 TI - Adults with physical disabilities in institutional care: do they have a choice? PMID- 8349402 TI - Clinical application of contact lens telescopes. PMID- 8349403 TI - Employment rates for compensatable spinal injuries in Australia. PMID- 8349404 TI - Handicapped parents with non-handicapped dependants. PMID- 8349405 TI - Facilitating discrimination learning for persons with developmental disabilities. PMID- 8349406 TI - Depression and anxiety in families with a mentally handicapped child. PMID- 8349407 TI - Disability and the law of employment. AB - Following disappointment in Canada with the results of human rights legislation and a revival of interest in quota systems for the employment of disabled people, the author made a study of the quota system operating in Japan. This article describes the system and some of its problems. The author then seeks to assess the potential of a quota law that includes strong financial incentives for compliance. The author concludes that laws to compel the employment of disabled people have little potential for achievement, and that they may well be counter productive. The most promising avenues for the improvement of employment opportunities for disabled people lie outside the use of the law. However, some legal changes could help, and these are mentioned in the conclusion. PMID- 8349408 TI - Parental attitudes to out-of-home placement of young children with developmental disabilities. AB - The study tested the research construct that parental inclination to apply for out-of-home placement for their young children with developmental disabilities (up to 5 years) was a function of their stress levels, sense of coherence, and social support received from formal and informal resources. Sixty-one parents (out of 80) of children diagnosed as developmentally disabled in the central western part of Israel participated in the study. The construct above was confirmed, as the sense of coherence and informal social support moderated the levels of stress and parental consideration of out-of-home placement for the young child. In brief, parents that favoured raising their developmentally disabled children at home had high levels of sense of coherence and a strong informal support system. Findings are interpreted with respect to practice and previous research. PMID- 8349409 TI - Comparison of 55% TFA/CH2Cl2 and 100% TFA for Boc group removal during solid phase peptide synthesis. AB - Two parallel syntheses of 40 C-terminal amide peptides, ranging in length from 4 to 20 residues, have been carried out using simultaneous multiple peptide synthesis. All synthetic steps, other than the removal of the Boc group, were performed simultaneously under identical experimental conditions. The two sets of peptides were deprotected with either 55% TFA/DCM for 30 min or 100% TFA for 5 min. The purity of the peptides obtained when deprotecting with 55% TFA/DCM was, on average, 9% higher than with 100% TFA. The major impurity obtained during synthesis when 100% TFA was used for Boc removal corresponded to the omission of the second amino-acid residue added. Volumetric measurements of the swelling of the resin in the different deprotection solvents were carried out. These showed that the omission analogs generated are probably due to insufficient swelling of the resin, resulting in limited solvent transfer of 100% TFA into the resin and, in turn, incomplete Boc removal. PMID- 8349410 TI - Synthesis and biological activity of a destruxin analogue: D-Lac-6 destruxin E. AB - A general strategy for the synthesis of destruxin analogues is described and applied to a particular example, D-Lac-6 destruxin E. The tetrapeptide Boc-Ile-N MeVal-N-MeAla-beta-Ala-OMe (2) was chosen as the basic starting compound, and its preparation was optimized. This fragment was then coupled with the compound (D)Lac-Pro, and the resulting peptide was cyclized by the DEPC or DPPA/HOBt/DMAP methods at 21 and 30% yield, respectively. The biological activity of the analogue obtained was established by injection to an insect host. PMID- 8349412 TI - Recombinant human brain-derived neurotrophic factor (rHuBDNF). Disulfide structure and characterization of BDNF expressed in CHO cells. AB - Three disulfide linkages of recombinant human brain-derived neurotrophic factor (BDNF) were determined by peptide sequence analysis and characterized by mass spectrometry. The three disulfide bonds for BDNF expressed in Chinese hamster ovary cells include Cys-13-Cys-80, Cys-58-Cys-109 and Cys-68-Cys-111, and the disulfide structure was homologous to that of nerve growth factor. PMID- 8349411 TI - Surface-induced conformational switching in amphiphilic peptide segments of apolipoproteins B and E and model peptides. AB - The conformational and surface-binding properties of a synthetic peptide corresponding to Tyr-apolipoprotein B-100(1000-1016) amide, SP-4, which was previously shown to mimic the focal accumulation pattern of LDL on the healing de endothelialized rabbit aorta [Shih et al. (1990) Proc. Natl. Acad. Sci. USA 87, 1436-1440], have been investigated. SP-4 behaves as an amphiphilic alpha-helical peptide at the air-water interface and bound to siliconized quartz slides. However, its N alpha-acetylated analogue formed beta-sheet structures at the air water interface. Nonhomologous peptide models of SP-4 also exhibited mixed alpha helical and beta-sheet surface-binding behavior. Peptides corresponding to the cationic apolipoprotein (apo) B/E receptor binding regions of apoE (SP-2) and apoB (SP-11) were also studied. SP-2 behaved as an amphiphilic alpha helix, but, surprisingly, SP-11 formed surface-induced beta-sheets. These results demonstrate that all of the peptides studied have surface-binding properties, and suggest further that either alpha-helical or beta-sheet peptide structures may determine the binding of LDL to the arterial wall or the apoB/E receptor. PMID- 8349413 TI - The beta-bend ribbon spiral. Synthesis and conformational analysis in solution and in the crystal state of depsipeptides containing alpha-hydroxyisobutyric acid. AB - The synthesis and conformational analysis in solution (by FTIR absorption and 1H NMR) and in the crystal state (by X-ray diffraction) of three Hib-containing depsipeptides have been performed. In the crystal state Z-Aib-Hib-Aib-OMe is folded into a type-III beta-bend, while the conformation adopted by Z-Aib-Hib)2 Aib-OMe is a beta-bend ribbon spiral, characterized by two type-III beta-bends with Aib(1)-Hib(2) and Aib(3)-Hib(4) as corner residues, respectively. Both independent molecules in the asymmetric unit of t-Boc-L-Ala-Hib-L-Ala-OMe crystals are folded into a type-II beta-bend. For the Aib-Hib depsipeptides the conformation adopted in the crystal state is also that largely prevailing in solution, whereas for t-Boc-L-Ala-Hib-L-Ala-OMe the beta-bend conformation is significantly less populated in solution. A comparison is also made with: (i) the published crystal-state conformations of fully protected -(Aib)3-, -(Aib)5-, and L-Ala-Aib-L-Ala- sequences and the beta-bend ribbon spiral generated by (Aib-L Pro)n oligomers, and (ii) with the herewith described solution preferred conformation of Z-L-Ala-Aib-L-Ala-OMe. The possible use of Hib as an isosteric replacement for Aib in the design of conformationally constrained depsipeptides is briefly discussed. PMID- 8349414 TI - H-Gly-His psi (NHCO)Lys-OH, partially modified retro-inverso analogue of the growth factor glycyl-L-histidyl-L-lysine with enhanced enzymatic stability. AB - A partially retro-inverso analogue of the natural growth factor GHK was synthesized, in which the -CONH- bond between histidine and lysine was modified as -NHCO-. This modification is not expected to perturb the spatial distribution of the side-chains, and therefore the binding processes, compared to the native peptide. In the synthesis of the analogue two possible systems for deblocking of N pi-Bom group of histidine have been applied and compared. An alternative method is also described for the incorporation of malonyllysine into the peptide chain. When evaluated with respect to resistance toward degradation by human plasma in vitro, the new peptide analogue showed approximately a ten-fold increase in stability versus the parent peptide. PMID- 8349415 TI - Binding of calcium to synthetic peptides containing gamma-carboxyglutamic acid. AB - The Ca2+ binding properties of various gamma-carboxyglutamic acid (gla) containing synthetic peptides with counterpart sequences in human protein C were investigated employing potentiometry with a Ca(2+)-selective electrode and titration calorimetric techniques. The shortest peptides, FL(gla)(gla)LR, DF(gla)(gla)AK, and the oxidized form of the cyclic hexapeptide CI(gla)(gla)IC, each of which contains one pair of gla residues, have a weak affinity for Ca2+, with some peptides probably involved in intermolecular bridging of the Ca2+. The best example of this is the oxidized form of the peptide, CI(gla)(gla)IC, where one g-atom of Ca2+ interacts with 2 mol of peptide (n = 0.5) with a Kd value of 1.6 mM. A second g-atom of Ca2+ interacts with 2 mol of this same peptide (n = 0.5) and is characterized by a Kd of 8.8 mM. A longer peptide containing this same sequence, viz. L(gla)R(gla)CI(gla)(gla)IC, possesses two binding sites (n = 2.0) for Ca2+ of Kd = 16.1 mM, as well as a tighter site (n = 1), of Kd = 0.4 mM. An increase in stoichiometry of tight binding sites as the peptide is elongated is observed from binding data obtained on a 38-residue peptide that possesses all nine of the gla-residues of protein C in their proper sequence positions. The strongest Ca2+ binding sites (n = 3-4) possess an average Kd of 0.4 mM, followed by another class of sites (n = 5-10, average Kd = 1.5-3.0 mM). The affinity and stoichiometry of these stronger sites mimic those observed for binding of Ca2+ to the gla region of prothrombin fragment 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349416 TI - Identification and suppression of decomposition during carbodiimide-mediated reactions of Boc-amino acids with phenols, hydroxylamines and amino acid ester hydrochlorides. AB - N-tert-Butoxycarbonylamino acids (Boc-Xaa-OH) were coupled with p-nitrophenol (HONp) in dichloromethane using N,N'-dicyclohexylcarbodiimide (DCC) and N-ethyl N'(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), and the products were identified and quantitated by high-performance liquid chromatography. Boc-Xaa-OH with Xaa = Val was coupled also with pentafluorophenol (HOPf) and hydroxy containing additives (HOR), and the products were similarly determined as the methylamides. EDC-mediated reactions of Boc-Xaa-OH gave 8-25% of Boc-Xaa-Xaa-OR as well as Boc-Xaa-OR for R = Ph, Np, Pf, benzotriazole (Bt) and 5-norbornene endo-2,3-dicarboxamide; DCC-mediated couplings, 5-7% for R = Np and Bt. No dimer was formed in couplings with N-hydroxysuccinimide or 3-hydroxy-4-oxo-3,4-dihydro 1,2,3-benzotriazine. Dimerization was eliminated from DCC-mediated reactions by the addition of 1 equiv. of N-methylmorpholine, from the EDC-mediated reactions by carrying them out in pyridine. Dimerization is attributed to formation of the intermediate 2-alkoxy-5(4H)-oxazolone that undergoes fragmentation to the N carboxyanhydride, which reacts with the alcohol giving amino acid ester. Ester produces dimer by aminolysis of the O-acylisourea. Decomposition (1.4%) was also detected by analysis for H-Val-Phe-OMe in DCC-mediated reactions of Boc-valine with H-Phe-OMe, and was demonstrated to be caused by the hydrochloride of the ester salt that had been neutralized with N-methylmorpholine. Decomposition was eliminated by the addition of 5% of pyridine, which also had the beneficial effect of suppressing N-acylurea formation. PMID- 8349417 TI - SCF-MO study of the polyhydration of N,N'-dimethylmalonamide. AB - The effect of hydration on the conformation of the N,3 nylons has been studied using AM1 SCF-MO on the model molecule N,N'-dimethylmalonamide (NNMA). The polyhydration model has been used, so that only the water molecules directly bonded to solute molecule are considered. The study reveals that, although hydration induces dramatic changes in the torsional angles of the molecule, the new conformation still remains in the helical region of the Ramachandran map. PMID- 8349418 TI - On the side-reaction of N-alkylation of amino groups during hydrogenolytic deprotection in alcohol-containing solvents. PMID- 8349419 TI - Infectious crystalline keratopathy. PMID- 8349420 TI - Ocular infections in the acquired immunodeficiency syndrome. PMID- 8349421 TI - Acute retinal necrosis and similar retinitis syndromes. PMID- 8349422 TI - Ocular microsporidiosis. PMID- 8349423 TI - Rapid diagnostic tests for infectious ocular disease. AB - There is a current and ongoing need for the rapid, accurate diagnosis of ocular infection and the prompt initiation of appropriate therapy to prevent visual loss, maximize use of health care resources, and reduce physicians' medicolegal liability. For the busy clinician, and ideal rapid diagnostic test to determine ocular pathogens would be one whose result is available before the patient leaves the doctor's office, so that optimal treatment can be promptly instituted. Today, the major rapid diagnostic tests available to the busy clinician are the clinical examination and the stained microscopical smear of conjunctival and corneal specimens. The latter technique is grossly underutilized and would contribute significantly to improved accuracy in early diagnosis of ocular infections. In the near future, improved enzyme immunoassays and simplified PCR kits will provide for highly sensitive and specific diagnostic capabilities for detecting ocular pathogens in the laboratory and, possibly, office settings. PMID- 8349424 TI - Role of the fluoroquinolones in ophthalmology. PMID- 8349425 TI - New horizons in antibacterial antibiotics. PMID- 8349426 TI - Contact lens-related infectious keratitis. AB - Infectious keratitis is the most serious complication of contact lens use. Virtually all contact lens wearers are at risk. Initial therapy consists of frequent broad-spectrum fortified antibiotic drops after appropriate laboratory workup. Pseudomonas and Acanthamoeba species are the most important causes of contact lens-associated ulcers. Acanthamoeba keratitis produces significant ocular morbidity, and treatment is not always effective. Recent studies have provided new insights regarding the incidence, risk factors, and pathogenesis of contact lens-related infectious keratitis. Extended-wear soft contact lens wearers are at greatest risk. With our present understanding of the pathogenesis and risk factors of contact lens-related infectious keratitis, daily-wear schedules are strongly advised. Even under the best of lens care conditions, infectious keratitis may still occur. It is therefore imperative that patients be informed to remove their lenses and seek medical evaluation if any discomfort develops. PMID- 8349427 TI - Postoperative endophthalmitis: pathogenesis, prophylaxis, and management. PMID- 8349428 TI - Postoperative chronic microbial endophthalmitis. PMID- 8349429 TI - The ocular manifestations of Lyme disease. AB - Lyme disease (with its ocular manifestations) is a worldwide disorder that is rapidly increasing in frequency. It is a treatable, multisystemic disease that presents in three stages of severity. It can present with unusual forms of conjunctivitis, keratitis, cranial nerve palsies, optic nerve disease, uveitis, vitritis, and other forms of posterior segment inflammatory disease. A patient with any of these ocular manifestations should be questioned for exposure to an area endemic for Lyme disease, tick bites, skin rash, or arthritis. Such patients should undergo serological testing. If the clinical presentation is suggestive of Lyme disease, a course of oral antibiotics should be used (unless the patient gives a history of adequate therapy). Topical corticosteroids can be used for anterior segment inflammation. An antibiotic therapeutic trial can be used for posterior segment or neuroophthalmic disease. Systemic corticosteroids without concomitant antibiotics should not be used in the treatment of ocular Lyme disease. If ocular Lyme disease is discovered and treated early, response to therapy is usually satisfactory. PMID- 8349430 TI - Chloroquinoxaline sulfonamide: a sulfanilamide antitumor agent entering clinical trials. AB - Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It does not appear to inhibit folate metabolism as does the structurally similar sulfaquinoxaline. Preclinical toxicology studies in dogs and rats have shown that CQS is toxic to lymphoid organs, bone marrow, gastrointestinal tract, pancreas, CNS, adrenal glands and testes. Toxicity was generally reversible with the exception of testicular atrophy in dogs and rats which occurred late and was not reversible within the study time frame. The pharmacokinetic data indicate that CQS binds to serum proteins in a dose and species specific manner. Terminal half lives appear to vary between species from 60 hours in mice, 15 hours in rats, and 45-132 hours in dogs. Preliminary data indicate a longer terminal half-life in humans. Two phase I trials are ongoing using a 60 min infusion schedule once every 28 days. The starting dose for each trial was 18 mg/m2. PMID- 8349431 TI - Cytotoxicity of crotoxin on murine erythroleukemia cells in vitro. AB - The cytotoxic effect of crotoxin, a heterodimeric phospholipase A2 from the venom of Crotalus durissus terrificus, was examined on murine erythroleukemia cells in vitro. Crotoxin cytocidal effect on cell growth had an EC50 of approximately 0.1 0.2 microM (3.0-5.0 micrograms/ml) in serum-free medium. Cytotoxicity was independent of cell growth since both quiescent and proliferating cells had similar sensitivities to the toxin. Dissociation of the crotoxin complex and phospholipase A2 activity of its subunit B are required for cytotoxicity, since the covalently linked crotoxin complex or the specific alkylation of the active site on the subunit B abolish the cytotoxic activity on murine erythroleukemia cells. Specific interaction between crotoxin and murine erythroleukemia cells appears to be required since the homologous phospholipase A2 from Crotalus atrox venom, with a higher phospholipase A2 specific activity than crotoxin, was 86 fold less potent than crotoxin. The data in this report show that the cytotoxic effect of crotoxin on murine erythroleukemia cells is consistent with the specific binding of the toxin resulting in cytocidal action mediated by the phospholipase A2 activity of crotoxin subunit B. PMID- 8349432 TI - A phase I clinical and pharmacokinetic study of the oral and the oral/intravenous administration of menogaril. AB - Thirty-five patients with advanced refractory cancer were enrolled on this phase I study of menogaril administered orally every 4 weeks at dosages ranging from 85 mg/m2 to 625 mg/m2. An additional 12 patients received alternating oral and IV doses of menogaril (250 mg/m2 IV; 250-500 mg/m2 oral) with accompanying blood and urine sampling for pharmacokinetics analysis. Nausea and vomiting were the dose limiting toxicities at the 625 mg/m2 dosage level; vomiting was inadequately relieved by prophylactic antiemetics at this dosage level. Other toxicities included sporadic leukopenia at all dosage levels; at dosages of 500 mg/m2 and 625 mg/m2, leukopenia < 3000/microliters occurred in 7 of 24 patients. Anemia and thrombocytopenia were much less frequent toxicities. Among the patients receiving IV menogaril, peripheral vein phlebitis, leukopenia and anemia were the predominant toxicities. No antitumor responses were observed, yet one patient with non-small cell lung cancer experienced a 30% reduction in metastatic tumor nodules. For the patients receiving alternating oral and IV menogaril, comparative pharmacokinetic analyses were performed by HPLC. After oral administration, maximum plasma concentrations were achieved in an average of 6 hours; maximum plasma concentrations were less than one-quarter of those achieved after intravenous administration. The harmonic mean (+/- SD) terminal disposition half-life after oral dosing was 29.3 +/- 9.2 hours; mean systemic bioavailability was 33.6 +/- 10.5% after oral dosing. Forty-eight hours after an oral dose, mean cumulative urinary excretions of menogaril and the primary metabolite, N demethylmenogaril, were 4.00 +/- 0.96% and 0.44 +/- 0.16%, respectively. Because of the poor tolerance of oral menogaril and minimal evidence of biological activity, this schedule of drug administration is not recommended for phase II evaluation. Based on this and other published studies of oral menogaril, frequent chronic low-intermediate dosages of the drug may be given orally with potentially better tolerance and antitumor activity. PMID- 8349433 TI - Phase I trial of dihydrolenperone in lung cancer patients: a novel compound with in vitro activity against lung cancer. AB - Antitumor activity of the butyrophenone dihydrolenperone in non-small cell lung cancer was initially suggested by in vitro screening against tumor cells derived from fresh surgical samples using the human tumor colony-forming assay. We have completed a directed phase I trial in patients with lung cancer. Thirty-two patients with lung cancer have completed 25 courses of therapy at doses of 10 to 60 mg/square meter orally on a twice daily schedule. Twenty-three men and 9 women with a median age of 55 (range 24-69) were entered. Twenty-four were performance status 0 or 1 and 8 were 2. The maximum tolerated dose was 50 mg/square meter orally twice daily and the dose limiting toxicity was somnolence. Of the 32 patients, 18 developed symptomatic hypotension (grade 1 or 2). There was no significant hematologic, renal, or hepatic toxicity. In vitro drug testing using the MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (thiazolyl blue)] assay confirmed 50% inhibition of non-small cell and small cell lung cancer cell line growth at 70-450 micromolar concentrations. Plasma dihydrolenperone levels were at least 75-fold less than levels at which in vitro activity was observed. We conclude: 1) the maximum tolerated dose in our study is 50 mg/square meter orally twice daily, 2) the dose-limiting side effect of dihydrolenperone is somnolence, and 3) the concentrations of dihydrolenperone observed in plasma are significantly lower than those associated with in vitro activity. PMID- 8349434 TI - Phase II study of alpha-interferon and 13-cis-retinoic acid in metastatic melanoma. AB - The combination of alpha-interferon and 13-cis-retinoic acid has shown significant activity against a number of human tumors. We conducted a phase II trial to test whether the combination would have a major response rate of 30% or more in patients with refractory, metastatic melanoma. Eleven patients were treated on the study. Alpha-interferon was administered subcutaneously three times a week at a dose of 10 million U/m2 and 13-cis-retinoic acid was administered orally at a dose of 1 mg/kg/day. No patient achieved a partial or complete remission. The combination of alpha-interferon and 13-cis-retinoic acid is unlikely to have significantly higher therapeutic activity than alpha interferon alone. PMID- 8349435 TI - Amonafide treatment of refractory esophageal cancer. A Southwest Oncology Group study. AB - Amonafide, a synthetic benzisoquinolinedione, was evaluated for treatment of squamous esophageal cancer. Eleven men and 5 women were eligible with a median performance status of 1 and median age of 63 years. Six had no prior treatment. All patients had measurable disease. Therapy consisted of amonafide 300 mg/m2d days 1-5 every 21 days. Thirty-five courses of therapy were delivered. The median number of courses received was two. Sixteen patients are evaluable for toxicity. Thirteen are evaluable for response. Toxicity was severe. Seven patients were hospitalized for toxicity. Six patients had grade IV granulocytopenia; two, grade IV thrombocytopenia. Angioedema developed in one patient; severe exfoliative dermatitis in another. A single partial response, with the decrease in size a supraclavicular node, was noted in a previously untreated patient. Amonafide, in this dose and schedule, is associated with occasionally severe toxicity precluding its likely use in squamous cell esophageal carcinoma. PMID- 8349436 TI - A phase II trial of deoxyspergualin in recurrent squamous cell head and neck cancer. AB - Fifteen patients with recurrent squamous cell head and neck cancer were treated with deoxyspergualin. There were no objective responses in 14 evaluable patients. The most common toxicity was reversible hypotension, which prompted dose reduction in nine patients. Deoxyspergualin is not recommended for the treatment of squamous cell head and neck cancer. PMID- 8349437 TI - Phase II trial of 13-cis-retinoic acid plus interferon-alpha in recurrent head and neck cancer. AB - 13-cis-retinoic acid (isotretinoin) and interferon-alpha have limited activity as single agents in advanced cancer. Preclinical data indicate that these agents have different mechanisms of action and, in combination have greater activity (that is, the ability to modulate growth and differentiation) in a number of malignant cell types than either agent alone. In clinical trials, the new biological regimen of 13-cis-retinoic acid and interferon-alpha was shown to have major activity in advanced squamous cell carcinoma of the skin and cervix. We conducted a phase II trial of this regimen in recurrent squamous cell carcinoma of the head and neck. Of the 21 evaluable patients, none had a complete response, and only one had a partial response (5%). Two patients had minor responses, four had stable disease, and 14 experienced disease progression. Five patients developed grade 3 toxic effects, including skin toxicity, fatigue, headache, and anorexia/weight loss. The median survival duration was 25.5 weeks (range, 4-95). The combination of 13-cis-retinoic acid and interferon-alpha at this dose and schedule is ineffective for the treatment of recurrent squamous cell carcinoma of the head and neck. PMID- 8349438 TI - Multicenter phase II study of brequinar sodium in patients with advanced gastrointestinal cancer. AB - Eighty-six patients with advanced colorectal, gastric or pancreatic carcinoma and no prior exposure to chemotherapy were treated with brequinar sodium. Brequinar was administered at a median weekly dose of 1200 mg/m2 intravenously. The toxicity was moderate, with thirty patients (35%) experiencing grade 3 or 4 toxicity. Objective responses were observed in 1/32 evaluable colorectal and 2/29 evaluable gastric carcinoma patients. There were no objective responses in 17 evaluable pancreatic cancer patients. We conclude that, at this dose and schedule, brequinar does not have sufficient activity in these gastrointestinal malignancies to warrant further evaluation. PMID- 8349440 TI - Phase II trial of doxorubicin and trifluoperazine in metastatic breast cancer. AB - Pre-clinical and clinical studies have shown that trifluoperazine (TFP) can modulate multidrug resistance. We have performed a Phase II trial of TFP and doxorubicin in doxorubicin-naive patients with metastatic breast cancer. We hypothesized that TFP would inhibit the development of doxorubicin resistance, resulting in an increased rate of complete response or a prolongation in response duration. Twenty patients with metastatic breast cancer were treated every 3 weeks with TFP 5 mg by mouth every 6 hours on days 0-5 and doxorubicin 60 mg/m2/96 hr on days 1-4 by continuous intravenous infusion. The first 5 patients were treated with TFP 15 mg by mouth every 6 hours, but the dose was reduced to 5 mg every 6 hours when grade 3-4 extrapyramidal toxicity was noted in 3 of the first 5 patients. Thereafter, neurologic toxicity was grade 0-2. No complete and 9 partial responses were produced in 20 patients (45%). The median response duration was 17 weeks (range 7-112). The combination of trifluoperazine and doxorubicin did not seem to produce a response rate or duration markedly different than that expected for doxorubicin alone in patients with metastatic breast cancer. Alternative trial designs may be necessary in future clinical trials investigating the inhibition of acquisition of drug resistance. PMID- 8349439 TI - Phase II study of etoposide and alpha-interferon in patients with advanced measurable colorectal carcinoma. AB - Based on encouraging in vitro and in vivo data, 14 consecutive patients with measurable metastatic previously untreated colorectal carcinoma were treated with a combination of intravenous etoposide and subcutaneous alpha-interferon. Etoposide was given at 60 mg/m2 intravenously on days 1-5 and alpha-interferon at 5 million units/m2 subcutaneously on days 1-5; courses were repeated every 21 days. All 14 patients were evaluable for response and toxicity. None of the patients achieved a complete or partial remission. Toxicity of this combination was moderate. Our data suggest that this combination is ineffective against colorectal carcinoma. PMID- 8349441 TI - New formulation intravenous melphalan in the treatment of patients with metastatic renal cancer. PMID- 8349442 TI - The Ethiopian immigrations to Israel--Medical, epidemiological and health aspects. PMID- 8349443 TI - The demography of the Ethiopian community in Israel. PMID- 8349444 TI - A medical care program for Ethiopian Jewish migrants in Addis Ababa. AB - In May 1990, the Ethiopian Jews--who for centuries had lived as peasants in isolated rural villages in northwestern Ethiopia--migrated en masse to Addis Ababa. In July, 39 deaths occurred in this community of approximately 22,000 people. When this was reported in Israel the Ethiopian Jews already living there staged a demonstration at the Knesset claiming that their relatives in Ethiopia were being neglected by the Jewish organizations providing aid to the Ethiopian people. In response, the American Jewish Joint Distribution Committee rapidly developed a comprehensive medical program during a 3-week period commencing on August 20. During the ensuing months there was a rapid fall in the mortality rate in the Jewish community. On 24-25 May 1991, as rebel armies were preparing to enter the city, almost the entire Jewish population remaining in Ethiopia was airlifted to Israel. PMID- 8349445 TI - Health profile of Ethiopian immigrants in Israel: an overview. AB - The health profile of two groups of Ethiopian immigrants in Israel was evaluated. Trichophytosis and active trachoma were observed in 5%-8.7% of prepubertal children. Among adults 13% had corneal opacities and 10.4% had cataracts. Goiter, spastic bronchitis, valvular heart disease, leprosy and onchocerciasis were prevalent. Malnutrition was common, with average body weights ranging from 72.4% to 85.2% of normal. Anemia was observed in 6.3% of young children and 70% of all immigrants. Fifty percent of children over 12 years and 98% of adults over 40 years of age had been exposed to hepatitis B virus; 9.8%-11.8% were HBsAg carriers. Tuberculin tests were positive in 9.8%-13%; and intestinal parasites were identified in 86%-98%. Hospitalization was required for 15.7% of immigrants arriving during the period 1978-90, and for 3.7% of those arriving in mid-1991 (Operation Solomon). PMID- 8349446 TI - Prevalence of diabetes mellitus in Ethiopian immigrants: comparison of Moses and Solomon immigrations. AB - The prevalence of diabetes mellitus and the distribution of serum glucose levels among 254 immigrant Ethiopian Jews (Operation Solomon) were studied immediately after their arrival in Israel in 1991. No case of diabetes was found. Although the body mass index of this population was higher than those obtained in Operation Moses, the serum glucose levels in almost all age-groups were significantly lower. PMID- 8349447 TI - Prevalence of glucose intolerance in young male Ethiopian immigrants. AB - The prevalence of intolerance to glucose was compared between young immigrant Ethiopian Jews shortly after their arrival to Israel, a similar group of Ethiopians 2-3 years after their arrival to Israel, and young Israeli students. A relatively high prevalence of glucose intolerance was found in both Ethiopian groups, but we could not demonstrate any deterioration in glucose tolerance after 2-3 years of Israeli life-style in the Ethiopian groups. In spite of high blood glucose levels in response to 75 g glucose load, when compared to Israeli students the Ethiopians' fasting insulin levels and insulin response to 75 g of glucose was relatively low, suggesting a higher glucose threshold for insulin secretion. However, in the Ethiopians, impaired glucose tolerance was associated with hyperinsulinemia, suggesting that similar to some other populations glucose intolerance is associated with insulin resistance. PMID- 8349448 TI - Comparison of glucose tolerance, lipids and blood pressure in young male Ethiopians from two different immigrations, 1989 and 1991. AB - The prevalence of glucose intolerance and hypertension was compared between a group of 87 young Ethiopian males (age 21.6 +/- 2.8 years) from the post Moses immigration of 1989 (group 1) and 89 age-matched Ethiopian males (age 21.4 +/- 3.1) from the Solomon immigration of 1991 (group 2). Both groups demonstrated a relatively high, for age, prevalence of glucose intolerance: 5% and 8% in groups 1 and 2 respectively (not significant). However, group 1 had a higher glucose level 2 h after an oral glucose tolerance test (P < 0.05) and a higher level of HbA1C (P < 0.05) and fructosamine (P = 0.07), concomitant with a lower fasting insulin (P < 0.005), when compared with group 2. Group 2 had a significant increase in both systolic and diastolic blood pressure when compared with group 1 (P < 0.05, P < 0.005 respectively). Group 2 had higher blood pressure levels and higher fasting insulin than group 1, suggesting a relationship between insulin levels and blood pressure in this population. PMID- 8349449 TI - Lipids and lipoproteins among Ethiopian immigrants: comparison of operations Solomon and Moses. AB - Lipid and lipoprotein levels and body mass index were compared between two immigrations of Ethiopian Jews to Israel. Those who came in Operation Moses in 1984-85 were survivors of a long trek across hundreds of kilometers and severe food deprivation. Those who immigrated in Operation Solomon in 1991 were bussed from their villages to Addis Ababa where public health care and food were provided and a few months later they were airlifted to Israel. Total cholesterol among the Operation Solomon immigrants was higher than those obtained in Operation Moses in the different age-groups studied, in both sexes. High density lipoprotein-cholesterol was significantly higher and triglycerides lower in Operation Solomon compared with those of Operation Moses. Body mass indices of the Ethiopians in both immigrations were significantly lower than in the Israeli born population but those who arrived in 1991 were heavier than those in the 1984 85 Operation Moses. The data on the Ethiopian Jews who arrived in Operation Solomon were not affected by the environmental hardships experienced by those who arrived in the 1984-85 Operation Moses. Therefore their exposure to a Western life-style, such as smoking, contraceptive use, change in diet and its effect on arteriosclerosis, diabetes mellitus and coronary heart disease will be of great interest. PMID- 8349450 TI - Blood pressure and body mass index in Ethiopian immigrants: comparison of operations Solomon and Moses. AB - Blood pressure, height and weight of 122 male and 143 female Ethiopian Jews who immigrated to Israel in Operation Solomon (1991) were measured and compared with those of Ethiopian immigrants who arrived in Israel in 1984-85 (Operation Moses). Although the body mass indices of the Operation Solomon immigrants were much higher than those of Operation Moses, no significant differences were found in blood pressure measurements in any age-group or in either sex. Blood pressure in Operation Solomon immigrants increased with age and correlated with body mass index and triglyceride serum levels among males, but not females. No correlation was found between cholesterol levels and blood pressure measurements. PMID- 8349451 TI - Descriptive epidemiology of malignant tumors in Ethiopian Jews immigrating to Israel, 1984-89. AB - This descriptive epidemiological study analyzes the frequency of cancer after the arrival of Ethiopian immigrants as reported to the Israel Cancer Registry from 1984 to 1989. The study cohort comprised 8,272 individuals (estimated 4,253 males and 4,019 females) with 27,966 and 26,848 person-years observed for males and females, respectively. Overall cancer incidence in this migrant cohort was low for both genders compared to cancer incidence among Jews born in Israel. The standardized incidence ratio (SIR) (in percentage) for cancers at all sites was 39 [95% confidence interval (CI) = 22-64] and 63 (95% CI = 41-92) for males and females, respectively. Male primary liver cancer and female thyroid cancer had high SIRs. All other sites had either average or low SIRs. No cases of neoplasms were reported in the respiratory system. Except for primary liver cancer, digestive neoplasms had an inverse male: female ratio. PMID- 8349452 TI - Endemic goiter in Ethiopian Jews--possible pathogenetic factors. AB - Goiter size, thyroid function tests and thyroid cytology were studied in 100 immigrant Ethiopian Jews, 1-12 months after arrival in Israel on Operation Solomon (1991), who were referred for evaluation of goiter. Female-to-male ratio was 2.2:1. Hypothyroidism was rare (1%) whereas hyperthyroidism was frequently diagnosed (11%). Elevated thyroglobulin (TG) serum levels were found in 36% of the patients. Antithyroid antibodies were not detected. Thyroid cytology revealed rich colloid goiters in all patients. Thyroid carcinomata and chronic lymphocytic thyroiditis were not diagnosed. Both hyperthyroidism and elevated TG levels were found only in female patients and were equally distributed in patients maintained on either Israeli or Ethiopian diets. It is suggested that the major factors in the pathogenesis of endemic goiter in Ethiopian Jews are genetic and/or food goiterogens, with only a minor role for iodine deficiency. PMID- 8349453 TI - The prevalence of ectoparasites in Ethiopian immigrants. AB - Newly arrived Ethiopian immigrants in Israel were screened for ectoparasitic insects and mites. Of 304 individuals examined 65.1% were infested with the head louse (Pediculus humanus capitis). The infestation rate among children varied between 65 and 100%. Children aged 6-11 years were the most infested group and no differences between girls and boys were found. The infestation rate in children was significantly higher than that found in adults. Approximately 39% of those examined were infested with the body louse (Pediculus humanus humanus). The rate of infestation with this parasite was higher in adults than in children and higher in females than males. Ten percent of the immigrants examined were infested with the scabies mite (Sarcoptes scabiei) and 4.3% with the human flea (Pulex irritans). PMID- 8349455 TI - Tuberculosis case finding and treatment in Ethiopian immigrants to Israel, 1989 91. AB - In addition to the immigrants from Ethiopia who arrived in Israel during the period 1980-90, a particularly large number immigrated in 1991 including a concentrated group (Operation Solomon). The procedures and problems involved in tuberculosis case-finding and treatment in Ethiopia and in Israel are described. The prevalence rate of cases of active tuberculosis in those who immigrated in 1991 was 1.3/100 persons as compared with 1.9/100 in the 1984-85 immigration (Operation Moses). Among the 1991 immigrants the number of cases reported was 261. In 89% the site was pulmonary. After screening and treatment in Israel there were very few cases of relapse or death and few contact cases in the host population. Follow-up of case reporting from 1983 is updated and demonstrates that the majority of cases are detected and treated within 2-3 years of immigration. Since 1980, 771 cases of tuberculosis were reported in all immigrants from Ethiopia. PMID- 8349454 TI - Intestinal parasitic infection in operation Solomon immigrants. AB - Previous studies have documented a high infection rate of intestinal parasites in Ethiopian immigrants to Israel. As a result, current treatment recommendations are for mass treatment without prior screening tests. However, the group of 15,400 Ethiopian immigrants who arrived in Israel in May 1991 (Operation Solomon) represents a somewhat different population from those who had immigrated earlier. The 1991 immigrants had spent 9-12 months in Addis Ababa before their evacuation; the conditions there, together with the provision of medical care, may have resulted in lower infection rates for intestinal parasites. The purpose of this study was to determine the prevalence of intestinal parasites in these recent immigrants to assess whether mass treatment would still be appropriate. Random stool specimens were obtained from 80 residents of a population of 650 Ethiopian immigrants who were cared for at a Jerusalem clinic. Specimens were examined at the Ministry of Health Laboratory. Of the 80 specimens 45 had sufficient quantity of stool to perform the standard Richie concentration method. Pooling results from all 80 individuals revealed 60 (75.0%) positive specimens, 53 (66.3%) with at least one pathogenic parasite, and 21 (26.3%) with multiple pathogenic parasites. These data provide the first systematic information on intestinal parasitosis in immigrants from Operation Solomon and suggest that mass treatment in this group is appropriate. PMID- 8349456 TI - Mycobacterium bovis lymphadenitis complicating BCG immunization in an infant with symptomatic HIV-1 infection. AB - A 3-month-old infant with HIV-1 infection who recently immigrated from Ethiopia developed regional lymphadenitis and systemic symptoms subsequent to BCG immunization. She was suffering from axillary lymphadenitis ipsilateral to the BCG vaccination site, failure to thrive, unresolving fever and hepatosplenomegaly. Acid-fast bacilli were seen on staining and Mycobacterium bovis was isolated from the regional lymph node. The infant responded promptly to triple antituberculous therapy but died 2 months later from overwhelming pneumonia and respiratory failure. This case emphasizes the iatrogenic hazards of BCG immunization in HIV-1 infected infants. With the increasing prevalence of pediatric HIV-1 infection, indiscriminate BCG immunization programs should be reconsidered. While infants with asymptomatic HIV-1 infection at risk for tuberculosis should be immunized, BCG immunization should be withheld in those with symptomatic disease. PMID- 8349457 TI - Imported malaria from Ethiopia--end of an era? AB - The immigration of Ethiopian Jews to Israel in the 1980s resulted in the importation of over 2,000 cases of malaria, a major challenge to clinicians and public health officials alike. In contrast, in the massive airlift from Ethiopia in May 1991 and in the sporadic immigration that followed it, malaria prevalence was extremely low, reflecting the routing of the more recent immigrants through nonendemic areas. The dramatic fall in the appearance of new imported malaria cases should not lead to complacency, however, as malaria may still appear in Ethiopians and other immigrants as well as in Israelis returning from regions of the world where the disease is still highly prevalent. A corollary of this caveat is that vigilance in finding and eliminating Anopheles breeding places in Israel must not be allowed to falter. PMID- 8349458 TI - Management of chloroquine-resistant Plasmodium falciparum malaria in a pregnant Ethiopian immigrant--a case report. AB - Plasmodium falciparum malaria is infrequently recognized in Israel as a cause of infection during pregnancy. We expect that with increasing frequency physicians in Israel will confront patients with malaria. Special concern should be given to malaria in pregnancy because of its serious complications. Thus, prompt diagnosis and treatment are essential. While chloroquine is safe for use in pregnancy, drug resistance is common, especially with Plasmodium falciparum. There is concern about the safety of other antimalarial agents during pregnancy. We recently observed a case of chloroquine-resistant Plasmodium falciparum malaria during pregnancy in a new immigrant primigravida from Ethiopia. Malaria in patients from endemic regions is less severe than in nonimmune hosts. Therefore, we elected to follow the patient's parasitemia periodically without additional antimalarial treatment until after delivery. PMID- 8349459 TI - Serological markers for hepatitis B and treponemal infection among HIV carriers from Ethiopia. AB - A group of 52 HIV carriers among immigrants who arrived in Israel from Ethiopia in Operation Solomon, 1991, is described. A control group was randomly chosen from the same population. HBV serology and treponemal antibodies were obtained from both groups. The frequency of HBV markers was similar in both groups (70% among the HIV carriers and 78.8% in the controls). HBsAg was more frequently found among HIV carriers (20%) than in the control group (8.6%). Treponemal antibodies were common among HIV carriers (31%), and infrequent in the controls (3%). These data indicate that HIV infection in this community is linked to treponemal infection and that these carriers handle HBV less efficiently then HIV negative subjects. PMID- 8349460 TI - Seroprevalence of antibodies against Toxoplasma gondii among recently immigrating Ethiopian Jews. AB - Sera from 144 Ethiopian immigrants who arrived in Operation Solomon, 1991, living in three absorption centers in the Jezreel Valley were tested for antibodies against Toxoplasma gondii. Antibodies were found in 34% of the test group, with a rise in prevalence with age from 0% in the first decade to 46% in the > 40 age groups. The prevalence in the Ethiopians was higher than in Jewish kibbutz members (22.8%) and lower than in Arab villagers (55.8%). During the reproductive years (age 20-39) the rate of seroconversion is 1% per year, and screening of pregnant Ethiopian women for antibodies to T. gondii should be considered. PMID- 8349461 TI - Plastic surgery findings in Ethiopian immigrants. AB - We have encountered infrequent and unfamiliar types of morbid conditions requiring plastic surgery. We present here our clinical experience with five illustrative cases and discuss the typical features of each condition and its treatment. PMID- 8349462 TI - Obstetric performance in Ethiopian immigrants compared with Israeli parturients. AB - It was the aim of this study to evaluate the obstetric performance of Ethiopian Jewish immigrants in comparison to the general Jewish obstetric population. The study was performed at the Soroka Medical Center, Beer Sheva, which manages the busiest delivery ward in Israel. Between 1988 and 1991 a total of 20,047 non Ethiopian women (Group N) and 431 parturients of Ethiopian origin (group E) delivered at the Soroka Medical Center. Group E included a significantly higher percentage of grandmultiparous women than group N. Among diseases complicating pregnancy there was a statistically significant higher incidence of severe pregnancy-induced hypertension (PIH) in group E than in group N. Mild PIH and chronic hypertension were of comparable prevalence in both groups. The prevalence of class A diabetes mellitus was significantly lower in group E than in group N; the same trend was also observed for diabetes class B but without reaching statistical significance. There was no significant difference between the groups in the prevalence of polyhydramnios, postdatism and poor obstetric history, or fetal distress, s/p cesarean section, and prolapse of cord. Statistical analysis indicated a tendency towards significance for higher prevalence of premature rupture of membranes in group N. Malpresentations and malpositions were of similar prevalence in both groups. The incidence of premature delivery in group E showed a higher relative risk, suggesting a tendency of significance. The incidence of meconium-stained amniotic fluid in group E was significantly higher than in group N. There was no significant difference in the prevalence rates of placental complications such as placenta previa and abruption of placenta between the groups. The mode of delivery, the prevalence of complications during the third stage of labor, birthweight of infants and perinatal mortality were similar for both groups. In conclusion, the obstetric performance in Ethiopian Jewish immigrants is surprisingly similar to that of Israeli Jewish parturients. The only prominent pathology that does not seem to be related to life-style and nutrition is pregnancy-induced hypertension. PMID- 8349463 TI - Periodontal status among adult immigrants from rural Ethiopia. AB - Dental research has emphasized the importance of understanding the epidemiology and etiology of periodontal disease, the second most prevalent dental pathology. The World Health Organization includes periodontal health prevalence, according to the Community Periodontal Index of Treatment Needs (CPITN), in its Global Oral Data Bank. Recent immigrants to Israel from Ethiopia offer a unique and important opportunity for investigation. Seventy adults aged 35-45 years were examined. Dividing the dentition into six sextants (according to CPITN), on average, two sextants were found to be healthy and only 1.18 sextants revealed shallow or deep pockets. These results demonstrate a relatively healthy periodontal status, as compared both to Israeli adults and data from the WHO Data Bank. Periodontal health has traditionally been related to regular dental visits (professional teeth cleaning) and home oral hygiene maintenance (toothbrushing and flossing). This population of immigrants had never visited dentists or hygienists nor used toothbrushes or dental floss. The periodontal health of this population is therefore of particular interest. PMID- 8349464 TI - Psychopathological aspects of the Ethiopian immigration to Israel. AB - Of the 352 adult Ethiopian Jews who live in the city of Netanya and who immigrated to Israel during the last few years, 87 were examined for evaluation of psychopathology symptoms and also to verify which factors of their immigration and which absorption conditions were related to their psychopathology. The Physician's Outpatient Psychopathology Scale (211-POPS), as well as three other self-rating scales--The Satisfaction Scale, The Events en route to Israel Scale, and The Frequency of Visits to Family Physician Clinics Scale--were completed with the assistance of well-trained Ethiopian interviewers in the homes of the Ethiopian immigrants. The results prove that a high incidence of psychopathology still existed even after 5 years of residence in Israel. The main topics of dissatisfaction (more than 60% of the sample), in order of severity, were their level of fluency in Hebrew, their financial situation, the attitude of the religious institutions towards the Ethiopian community, and the degree of observance of religious customs in Israel. It was found that a high level of psychopathology was related to a high level of suffering on the journey to Israel. It was also found that psychopathology usually declined with the length of residence in Israel. A high incidence of psychopathology was found to be related to an increase in age and to a low level of education. PMID- 8349465 TI - Psychiatric diagnoses in hospitalized adolescent and adult Ethiopian immigrants in Israel. AB - In 1984-85 Operation Moses brought a mass immigration of Jewish Ethiopians to Israel. Many of these immigrants were children and adolescents who came on their own having left their families behind. Since that time the adolescent department at the Geha Psychiatric Hospital has had the major responsibility of caring for those Ethiopian adolescents who required psychiatric hospitalization. The present study compares the diagnoses and reasons for admission of Ethiopian adolescents in Israel with those of Ethiopian adults and Israeli adolescents. The results of this comparison show that Ethiopian adolescents in hospital had significantly higher rates of dissociative disorders than the other two groups and significantly lower rates of the major functional psychoses than Ethiopian adults and Israeli adolescents. In addition the Ethiopian adolescents had relatively low levels of nonspecific depressive symptoms and anxiety symptoms and were hospitalized for significantly shorter periods of time than the other two groups. PMID- 8349466 TI - Health education for Ethiopian immigrants in Israel, 1991-92. AB - A health education program was developed to address the immediate needs of 20,000 Ethiopian immigrants to Israel in 1991. This modular program included: the use of health services, nutrition, prescription medication use, prevention of home accidents, first-aid and personal hygiene. Using an anthropological orientation, the program attempted to bridge the cultural gap regarding the health promotion skills of this population that had moved from a developing country to a new, Western society in Israel. The program was implemented throughout the country by specially trained veteran Ethiopian immigrants, some of whom were also health professionals, using newly developed visual tools. Over 4,300 adults participated in the program between August 1991 and August 1992. The program was positively accepted by the participants, who expressed their satisfaction with the content and materials. The tools developed were deemed successful in their cultural sensitivity, flexibility to local needs, and clarity. We suggest that various modules of the program continue to be implemented in order to address the rapidly changing health behavior needs of the Ethiopian immigrants in Israel, and that new modules be developed. PMID- 8349467 TI - Health education for the Ethiopian community in the Negev. AB - The importance of health education as part of health enhancement programs is well accepted. The encounter with the Ethiopian Jews introduced a new set of problems, requiring a novel approach to old concepts. A project that was carried out during the last decade is presented. Three target populations were identified: the Ethiopian population with 851 participants, medical and community teams with 843 participants, and 138 Ethiopian instructors. An effort was made to make the interaction between these groups more coherent. The project included 65 series of activities: lectures, workshops, staff meetings and conferences. The major topics included medical, emotional, anthropological and behavioral issues. The project was initiated for immigrants of Operation Moses (1984-85), and reinforced in Operation Solomon (1991). A follow-up is presently underway to aid in the absorption of this unique community. PMID- 8349468 TI - A culturally specific educational program to reduce the risk of HIV and HBV transmission among Ethiopian immigrants to Israel: a preliminary report on training veteran immigrants as health educators. AB - We describe an educational intervention project that was designed to lower the risk of transmission of human immunodeficiency virus and hepatitis B virus among the Ethiopian immigrants of the 1991 Operation Solomon. The importance and uniqueness of this program lies in its attempt to integrate into one program two different sets of traditions and concepts, in a culturally acceptable manner to the target population. On the one hand were the traditions of the Ethiopian community and its concepts about health and disease; on the other, were the biomedical model and empowering/participatory methods needed for intervening in this sensitive and difficult area. We also describe a model for training people from within the community to bridge the cultural gap in a relatively short period of time. PMID- 8349469 TI - Waves of immigration to Israel. PMID- 8349470 TI - MR-angiography during spontaneous attacks of cluster headache: a case report. AB - Magnetic resonance (MR) angiography was performed during and between two spontaneous and untreated attacks in a 24-year old male patient with episodic cluster headache. The ipsilateral ophthalmic artery was observed to be markedly dilated during both attacks. No changes were seen in the internal carotid artery or any of the main arterial branches on either side. A repeat MR-angiography two weeks later when the patient was in clinical remission showed no abnormalities. Our present case report suggests that the MR technique provides a useful method for non-invasive angiography during spontaneous attacks of cluster headache. PMID- 8349471 TI - Effectiveness of a piroxicam fast dissolving formulation sublingually administered in the symptomatic treatment of migraine without aura. AB - In this study we evaluated the efficacy of a new preparation (Fast Dissolving Dosage Form--FDDF) of piroxicam (40 mg in a single sublingual dose) in the acute treatment of migraine. The study plan was of single blind type versus placebo and involved 40 patients with migraine without aura (according to the IHS Classification criteria) who had to take Piroxicam FDDF (or placebo) within 2 hours from the beginning of a migraine attack. Pain intensity and associated symptoms were evaluated in the basal condition and then monitored at serial intervals for 24 hours. In the group of patients treated with the active drug (n = 20), a significant reduction of pain intensity (Visual Analogue Scale) was observed after only 15 minutes (P = 0.0034). After an hour, headache has disappeared in 15 patients, become mild in 4 and remained unchanged in only one subject. Associated symptoms also quickly disappeared after Piroxicam FDDF administration and headache recurred in only two patients within the 24 hour period. Sublingual administration of Piroxicam FDDF was well tolerated: no systemic side-effects were reported and only two subjects complained about mouth dysesthesias which were described as mild and short-lasting. In conclusion, Piroxicam FDDF has been shown in this preliminary study to have striking efficacy in the acute treatment of migraine. The treatment is characterized by quick onset, long duration and good tolerability. PMID- 8349472 TI - The role of life event stress, coping and social support in chronic headaches. AB - A group of chronic headache sufferers (migraine and tension-type headache) was compared with two individually matched control groups of nonheadache subjects in terms of life event stress, and the stress moderating factors of coping skills and social support. The headache group did not differ from the control groups on the measures of life event stress or coping but significant differences arose on the measure of social support with the headache group achieving lower scores than the control groups. The findings were interpreted as suggesting that clinicians and researchers should pay more attention to social aspects of headaches, and that interventions aimed at teaching headache sufferers to mobilize social support should be considered as components of treatment packages. PMID- 8349473 TI - The relationship between perceived stress, social support and chronic headaches. AB - A group of chronic headache sufferers (migraine and tension-type headache) was compared with a group of nonheadache control subjects in terms of two domains of social support (social integration and functional support), perceived social support, sources of social support, and perceived stress. Headache sufferers and controls were not differentiated with respect to number of social relationships, sources of support and availability of support. In contrast, headache sufferers were significantly less satisfied with the support available to them and scored lower on all four types of functional support measured (appraisal, esteem, belonging and tangible). Support measures did not show a linear relationship with headache chronicity, and were at their lowest at an intermediate point in the headache history rather than at an early or late point. Headache sufferers scored higher on perceived stress than control subjects and differences between the groups increased as a function of headache chronicity. The findings were interpreted as suggesting that clinicians and researchers should focus greater attention on the social dimension of headaches. PMID- 8349474 TI - Headache in the writings of Moses Maimonides and other Hebrew sages. AB - In the history of philosophy, theology, and medicine, Maimonides shares the limelight with Arabic scholars such as Ibn Rushd, Ibn Sinna and Ibn Zuhr, chronologically between the great intellectuals of classical Greece and Rome and those of the later Middle Ages and early Renaissance. Maimonides was a very great philosopher and theologian, usually underrated by the historians. He was also an outstanding medical practitioner and teacher. Moses Maimonides had an incredible literary ability and an encyclopedic knowledge. He wrote extensively in the fields of theology, mathematics, law, philosophy, astronomy, ethics, and, of course, medicine. His medical writings are varied, comprising extracts from Greek medicine, a series of monographs on health in general and several diseases in particular, and a pharmacopoiea. The present essay extracts, primarily from Maimonides' medical writings, his pronouncements dealing with headache. Since most of Maimonides' pronouncements about headache in his Medical Aphorisms were derived from Graeco-Roman medical writers such as Hippocrates, and especially Galen, in regard to these statements Maimonides was merely a compiler--not an innovator. Some of his concepts about the causes of headaches being related to a dysequilibrium of the body humors are clearly medieval in origin. Other statements demonstrate this concern with preventive medicine and the maintenance of a healthy regimen of daily living. Medications to treat illness should only be used if non-medicinal means such as diet and exercise are not effective. The heritage of Maimonides' writings is being more and more appreciated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349475 TI - Taurine levels in plasma and cerebrospinal fluid in migraine patients. AB - Taurine is the amino acid with the highest concentration in the human body. Its physiologic functions are not yet well understood. As a neurotransmitter or neuromodulator it may display inhibitory functions. We have measured taurine levels in plasma and cerebrospinal fluid of migraine patients during attacks, comparing them with controls. Patients with migraine had significantly higher concentrations than controls. No sex or age influence over the amino acid levels were observed. Plasma taurine levels in patients with classic migraine correlated negatively with severity of headache. Central taurine liberation during migraine crisis may be due to spontaneous depolarization or a defensive reaction in the context of cerebral homeostatic processes. PMID- 8349476 TI - Painful intervertebral dysfunction: Robert Maigne's original contribution to headache of cervical origin. The Quebec Headache Study Group. AB - Professor Robert Maigne, a French Orthopedic Medicine and Functional Rehabilitation specialist, has put forward new concepts leading to a better understanding of common pain of spinal origin. Maigne explains that pain in the spine is due to an intervertebral dysfunction of the mobile segment which consists of the intervertebral disc, ligaments and the facet joints. Any benign mechanical dysfunction of the mobile segment can induce a pain radiating in the dermatome at the same level as the vertebral problem. Maigne also described signs found in the skin (cellulalgia), in the muscles (myalgic bands) and in the bony insertions of tendons (tenalgia). These signs are to be found in the same dermatome, myotome and sclerotome as the spinal dysfunction. For headache of cervical origin due to painful intervertebral dysfunction, the most frequent dysfunctional mobile segment is located at the C2-C3 level. This induces pain mostly in the posterior parts of the head and cellulalgia in the C2 and C3 dermatomes. Painful tumefaction is also found over the posterior aspects of the facet joints on palpation at this level. These findings are key elements for the diagnosis of painful intervertebral dysfunction. The recognition of these signs is changing our understanding of the role of the cervical spine in headaches. Painful intervertebral dysfunction is very frequently found in chronic daily headaches. PMID- 8349477 TI - Comparison of the efficacy between flunarizine and nifedipine in the prophylaxis of migraine. AB - BACKGROUND: Several calcium channel blockers have been evaluated in controlled clinical studies and some hold considerable promise for future. Efficacy in migraine prophylaxis has been claimed for drugs belonging to all three classes of calcium channel blockers (nifedipine-like, verapamil-like, and flunarizine-like), but the extent and quality of the evidence varies, and a comparison of efficacy between different calcium channel blockers has not been reported. OBJECTIVE: The objective of the study is to assess the comparison of efficacy and safety of flunarizine and nifedipine in migraine prophylaxis. PATIENTS AND METHODS: The study was conducted in a prospective, double-blind, randomized controlled trial, parallel group design. 78 patients were studied for a 1-month period during which all patients received placebo followed by a 3-month experimental period. Headache response to medication was measured monthly by compilation of migraine-scores derived from quantitative data recorded by patients in a daily diary. Student's t test was used to compare results from the flunarizine (10 mg) and nifedipine (20 mg) group for each month. RESULTS: Both groups showed a significant reduction in the migraine-scores after 3-months. No significant differences were detected between groups, but there was a clinical significantly different reduction of migraine-scores between the groups in the first month after the run-in period (58% vs 38%). It shows that the beneficial effect of flunarizine was more rapidly manifest than that of flunarizine. Tachycardia more frequently occurred in the nifedipine group than in the flunarizine treatment group. CONCLUSION: It concluded that flunarizine is a potentially more useful agent in the prophylaxis of migraine headache. PMID- 8349478 TI - The potential effectiveness of moclobemide, the new monoamine oxidase inhibitor, in the prophylaxis of migraine. PMID- 8349480 TI - Investigating the role of osteopathic manipulation in the treatment of asthma. PMID- 8349479 TI - Helping-not hurting--residents with substance use disorders. PMID- 8349481 TI - To sleep, perchance... PMID- 8349482 TI - Diagnosis and management of asthma: a brief review of two asthma expert panel reports. AB - During the past decade, asthma morbidity and mortality have increased noticeably. Although the reasons for the increase are not clear, the prevalence of asthma has been reported to be increasing not only in the United States but also in other countries throughout the world, including the United Kingdom, New Zealand, and Australia. Asthma mortality rates and morbidity trends are increasing despite what appears to be major scientific advances in our understanding of asthma and in the face of a multitude of new therapeutic modalities. This article presents a brief overview of the pathogenesis and diagnosis of asthma, and highlights the major management recommendations of two expert panel reports. PMID- 8349483 TI - Research secures the future of osteopathic medicine: Part 2: Readdressing the function and structure of colleges of osteopathic medicine. AB - Many problems exist within the contemporary medical education process in general and the osteopathic medical profession in particular. Part 2 of this series suggests that the single greatest impediment to solving these problems is an institutional infrastructure that is not congruent with the institution's functions, as defined in its mission statement. (This mission statement generally entails two primary goals: education and research). Two major divisions within the core's infrastructure are suggested: medical education and medical research. By restructuring their infrastructure, colleges of osteopathic medicine can more effectively address and support their primary functions of education and research. PMID- 8349484 TI - 'Blueprint' for creating classroom facilities in teaching hospitals. AB - Classroom facilities in teaching hospitals have evolved from simple rooms with blackboards to sophisticated amphitheaters with high-tech audiovisual equipment. This article presents a "blueprint," which was used in an osteopathic hospital, to renovate existing space into classrooms that are conducive to learning. PMID- 8349485 TI - Unexpected adverse effects of Freon 11 and Freon 12 as medication propellants. AB - Metered-dose inhalers are frequently used in treating pulmonary diseases associated with bronchoconstriction, chiefly asthma and chronic bronchitis. These aerosolized medications are not without the potential for adverse effects. The author describes two patients who likely had adverse reactions to the Freon propellants used in the inhalers. These reactions are reported in order to alert physicians to their possible occurrence and to suggest a rational treatment approach. PMID- 8349487 TI - Freud's brain: toward a unified neuropsychodynamic model of personality and psychotherapy. AB - Neuropsychological findings and principles are not by themselves sufficient to provide definitive answers to broad questions of personality, psychopathology, or psychodynamics, nor should they be seen as attempting to usurp other approaches. This review has briefly noted some of the directions in which neuropsychology is being applied to psychoanalysis and psychodynamic personality theory, as well as to clinical practice. The purpose of any model is to try to weave disparate observations and findings into a coherent theoretical framework that can be productively employed for further clinical and research purposes. To this end, the neuropsychodynamic approach can contribute. Man--as Freud recognized--is neither "organic" or "functional." He is both, and our commitment to psychological knowledge must entail a search for unities. PMID- 8349486 TI - Insight, empathy, and internalization: elements of clinical change. PMID- 8349488 TI - The impact of incest on identity formation in women. AB - In conclusion, the purpose of this paper was to elucidate some of the long-term impacts of the incest trauma on women. This includes its impact on identity formation. The process of idealization and the creation of an idealized image as a defensive and adaptive strategy to cope with overwhelming trauma was highlighted. This initially successful coping mechanism later causes problems in limiting the individual's self-perception and restricting her relationships with others. This is frequently manifested in problems that the adult survivor presents in regard to interpersonal relationships, as well as revictimization and an inhibition in identifying and expressing certain aspects of herself. The goal of treatment is therefore twofold. I am in agreement with Alpert (1991), van der Kolk (1987), and others who stress the importance of the validation and integration of the trauma and related affects through the recovery and reliving of past memories. Additionally, an analysis of the character structure that the person developed to cope with overwhelming and damaging experiences is essential. The achievement of a more cohesive, integrated sense of self for an adult survivor of incest can only be accomplished through the working through of past traumas and the understanding of its effect on identity development and character structure. This aspect of the treatment process was best expressed by one of my patients, who said, "the first part of my analysis dealt with remembering and reliving what happened to me, the second part is dealing with who I had to become and not become as a result of it." She later added that she felt the second part is even more difficult and challenging. PMID- 8349489 TI - The application of the core conflictual relationship theme method to Japanese psychoanalytic psychotherapy. PMID- 8349490 TI - What constitutes our understanding of a patient? AB - A number of approaches to the search for methodology in the human sciences are reviewed. Heidegger's use of Husserl's phenomenology led to his exploration of the background practices on which he believed all our understanding is based. This use of phenomenology was adopted by Sartre and R. D. Laing, and existential psychiatrists and psychoanalysts in their emphasis on the here-and-now encounter between the patient and the therapist, along with various embellishments and emendations on Heidegger's notion of what it meant to live authentically or inauthentically. Foucault maintained that there is a politics embedded in all the human sciences such as psychiatry and psychoanalysis, and this politics revolves around the use of power and its operations, including the actual use of the human sciences in the culture and what the different theories imply in the way of an ideology. Lacan emphasized this when he challenged the prevailing ideology of United States psychoanalysis, in which adaptation was seen as the crucial task of the ego. The existence of background practices and outer horizons required for any understanding in the human sciences leads to a situation that questions the use of empirical methods to establish what is accepted as "truth" in the human sciences. A predominant alternative, that of hermeneutics, has gained acceptance by eminent analysts such as Gill and certain interpersonal theorists. But the term hermeneutics is used in many ways by many authors and runs the danger of a relativism and a nihilism. This leads to a discussion of the value of various philosophical positions in throwing light on our search for a methodology in the human sciences. A review of arguments invoking the "end of philosophy" such as those of Rorty reveals that they are paradoxical and based on premises which in turn represent a philosophy. This debate remains unresolved. In general the postmodern view sees "truth" as more relative and emphasizes the role of social and cultural aspects of prevailing ideologies in constituting and determining what we call truth and understanding, including the "understanding" of a patient in psychotherapy. An example of the postmodern blend of philosophy and psychoanalysis is presented by Arlow's emphasis on unconscious fantasies and his insightful comments on how these unconscious fantasies organize and determine what we experience from the very beginning of life. This I believe is most consistent with Rescher's philosophical notion of "conceptual idealism," also briefly reviewed in this paper.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8349491 TI - Separation-individuation issues in sister transference. PMID- 8349492 TI - Ferenczi, RN, and the struggle for equal ground. PMID- 8349493 TI - Unconscious communication in Birdy. PMID- 8349494 TI - Ivar Johansson, 1891-1988: a brief biography. PMID- 8349496 TI - Body dimensions and carcass measurements of cattle selected for postweaning gain fed two different diets. AB - Genetic and phenotypic parameters among nine body dimensions and two measures of growth rate were estimated from measurements on 709 Angus and Hereford bulls and heifers born in 1984 and 1985. Height and width at hips, height at withers, body length, girth, head length and width, muzzle width, and cannon bone circumference were measured at weaning and again after 168-d postweaning gain tests. The cattle were from the final two calf crops of a 20-yr study to examine the response to selection for postweaning gain when fed either a high-concentrate diet or an all hay diet. Sources of variation included year of birth, breed, sire within breed, diet, age of dam, and the linear regression on calf age. Parameter estimates among the body dimensions and carcass measurements were also calculated using a subsample of 318 Hereford and Angus bulls fed until they achieved > or = 7 mm of subcutaneous fat. Yearling measurements from calves fed the high-concentrate diet were larger than those from calves fed the all-hay diet. Sire within breed, age of dam, and the regression on age of calf affected all measurements (P < .001) at both measurement times. Dietary energy concentration influenced all body measurements taken at the end of test. Heritabilities of all body measurements were moderate to high. The highest genetic correlations with gain were for cannon bone circumference, body length, and heart girth. The heritabilities of all body dimensions were sufficient to indicate that selection progress was possible, but the low genetic correlations with gain and carcass traits suggested that this may not be desirable. PMID- 8349495 TI - Ruminal escape protein for lightweight feedlot calves. AB - Effects of supplemental ruminal escape protein (REP) were evaluated in an 84-d growth study involving 140 feedlot steers (198 kg) and in a site of digestion study involving four steers (149 kg). Dietary treatments were as follows: 1) basal diet; 2) basal diet plus 2% of a REP blend (1/3 blood meal, 1/3 meat and bone meal, and 1/3 feather meal); 3) basal diet plus 4% REP; and 4) basal diet plus 6% REP. The basal diet contained 18% alfalfa hay, 10% sudangrass hay, 61% steam-flaked corn, 2.5% yellow grease, 6% molasses, and 2.5% supplement. The basal diet contained 12.2% CP, and urea was the sole source of supplemental N. There was a quadratic effect (P < .05) of REP supplementation on rate and efficiency of gain. The greatest response was with 2% REP, which increased rate and efficiency of gain by 13.4 and 8.4%, respectively, over that of the basal diet. Protein supplementation had a quadratic effect (P < .05) on the NE value of the diet. The addition of 2% supplemental REP increased the NE of the diet by 6.6%. In the site of digestion trial, supplemental REP linearly increased (P < .01) passage of nonammonia and amino acid N to the small intestine. Compared with estimated amino acid requirements and with muscle composition, postruminal supplies of arginine, histidine, lysine, methionine, and phenylalanine were the limiting amino acids in the basal diet. Excess bypass protein, by placing an additional demand on arginine for detoxification of ammonia, may limit growth and performance. PMID- 8349497 TI - Carcass traits and the occurrence of dark cutters in pregnant and nonpregnant feedlot heifers. AB - The objective of this study was to determine whether the occurrence of dark cutters and selected carcass traits differ between pregnant and nonpregnant feedlot heifers. Feedlot heifers (n = 8,292) were identified at slaughter as being either nonpregnant, pregnant with a moderate-sized fetus (midgestation), or pregnant with a large fetus (late gestation). This was based on visual appraisal of a gravid uterus at the evisceration table. After chilling (24 to 72 h), carcass data were collected. Cattle originated from 23 different commercial feedyards located within a 350-km radius of a commercial slaughter facility located in southwest Kansas. Across slaughter lots, the incidence of pregnancy varied from 0 to 25% with an overall mean of 4.74%. Carcass traits of heifers with moderate or large fetuses did not differ (P > .15). Compared with carcasses from nonpregnant heifers, carcasses from pregnant heifers were 4.5 kg lighter (P < .01), had .11 cm more fat thickness (P < .01), and exceeded the number of carcasses that graded Choice or Prime by 6% (P < .01). Carcasses from pregnant heifers had higher maturity scores (P < .01) and there was no incidence of dark cutters (P < .01) compared with a 1.7% incidence of dark cutters in carcasses from nonpregnant heifers. Any economical advantage in the pregnant heifers due to their higher percentage of Choice carcasses and lower incidence of dark cutters may be offset by their increased carcass fat thickness and lower dressing percentage. PMID- 8349498 TI - Cow weights and reproduction on native rangeland and native rangeland complementary forage systems. AB - Replicated cow herds of 15 Angus x Hereford (AH) and 15 Brahman x Hereford (BH) F1 cows each were placed on native rangeland (NR) or native rangeland complementary forage (NRCF) systems. The NR was 8.1 ha of sagebrush-mixed prairie per cow-calf unit and the NRCF used the same mixed prairie complemented by .4 ha of double-cropped winter wheat and summer annual forage replacing about 30% of the mixed prairie for each cow unit. Calving seasons, spring for NR and fall for NRCF, were selected to complement the respective forage systems. Cow weights, reproductive performance, and population demographics were measured through seven calf crops to investigate their relationship to forage systems and cow breed types. Seasonal average cow weights increased from 484 +/- 7 (SE) kg during calf crop 1 to a peak weight of 568 +/- 8 kg at calf crop 5. Average weight of AH cows was 514 +/- 3 kg, compared with 539 +/- 3 kg for the BH cows (P < .01). Angus x Hereford and BH cows were 38 and 44 kg heavier, respectively, on the NRCF system than on the NR system. The average percentage of reproduction for AH cows was 90 +/- 2%, compared with 87 +/- 2% for the BH cows (P < .13). Both breeds had approximately 87 (AH) to 89% (BH) reproductive rate on the NR system. In contrast, AH cows had 94 +/- 2% reproduction on the NRCF system, compared with 84 +/- 2% for the BH cows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349499 TI - Linear body measurements of cattle before and after 20 years of selection for postweaning gain when fed two different diets. AB - At weaning and again after postweaning gain tests, height and width at hips, height at withers, body length, girth, head length and width, muzzle width, and cannon bone circumference measurements were obtained from Angus and Hereford bulls and heifers born in 1964, 1984, and 1985 (n = 989). The cattle were from the initial and final two calf crops selected for postweaning gain when fed either a high-concentrate diet or an all-hay diet. Analysis of variance and canonical discriminant analysis were used to examine the relationships among body measurements and major sources of variation (breed, year of birth, sire within breed and year, diet, sex of calf, age of dam, and the regression on age of calf). Canonical discriminant analysis indicated that one underlying variate explained nearly 90% of the total variation among the weaning measurements, whereas three variates were required to account for that proportion in the end-of test measurements. At both measurement times, the first canonical variate was associated with year of birth, the second with sex of calf, and the third with dietary energy. Correlations between each canonical variate and the original body measurements indicated that year of birth (variate 1) was most closely associated with body length and cannon bone circumference at weaning and with body length and height at hips (but not withers) at end of test. Sex of calf (variate 2) was associated most closely with width of muzzle and head. Diet (variate 3) was associated with heart girth. Faster-growing cattle were longer in body, but not necessarily taller. PMID- 8349500 TI - Paternal half-sib heritabilities and genetic, environmental, and phenotypic correlation estimates from randomly selected Hereford cattle. AB - Growth and carcass data were collected during 10 yr at the Fort Keogh Livestock and Range Research Laboratory in Miles City, MT from a Hereford herd selected at random. The objective was to compare genetic parameter estimates from this randomly selected herd with estimates from published selection studies. Only bulls were included in the data set. Bulls were slaughtered between 14 and 17 mo of age. Genetic parameters were estimated by the paternal half-sib procedure. Data were subdivided into three subgroups: 1) all bulls that had birth weights, 2) bulls with complete records for growth traits, and 3) bulls with complete carcass and growth records. The heritability estimate for birth weight on 736 progeny from 86 sires was .18. The second group included 616 progeny representing 85 sires and heritability estimates were weaning weight, .17; daily gain from birth to weaning, .20; final test weight, .42; and daily gain on test, .47. The third group included 401 progeny from 75 sires and heritability estimates were carcass weight, .38; longissimus muscle area, .51; marbling, .31; slaughter weight, .42; and dressing percentage, .25. Thus, these estimates of heritability were in quite good agreement with previously published values, with a tendency for these estimates to be lower for early growth weights. Phenotypic and environmental correlations were in good agreement and genetic correlations were in general agreement with the data reviewed. Estimates of heritabilities from this herd selected at random were not larger than previous estimates from selected herds. PMID- 8349501 TI - Genetic and environmental parameters for mature weight and other growth measures in Polled Hereford cattle. AB - Variances and covariances were estimated for birth weight (BWT), weaning weight (WW), yearling gain (YG), yearling weight (YW), yearling height (YH), relative growth from birth to weaning (RGW) and weaning to yearling (RGY), and mature weight (MW). Field records on 572,446 Polled Hereford cattle were analyzed. Because multiple dam weights were collected on a cow the MW used in the analysis was calculated using a nonlinear regression correction factor computed by fitting a quadratic with a plateau to the data. If the cow had an observation(s) beyond the inflection point (IP), the closest weight to that point was used. If the cow only had observation(s) before the IP the closest weight to that point was nonlinearly adjusted to the plateau. The IP for this data set was 1,506 d and the plateau was 554.7 kg. Heritabilities and genetic and environmental correlations were calculated from the appropriate (co)variances and phenotypic correlations were computed. Heritability estimates for BWT, WW, YG, YW, YH, RGW, RGY, and MW were .49, .24, .23, .30, .59, .24, .15, and .52, respectively. Genetic correlations between MW with BWT, WW, YG, YW, YH, RGW, and RGY were .64, .80, .76, .89, .73, -.29, and .35, respectively, environmental correlations were .15, .43, .05, .40, 1.03, .32, and -.10, respectively, and phenotypic correlations were .33, .32, .28, .46, .70, .00, and .07, respectively. PMID- 8349502 TI - Direct and correlated responses to divergent selection for serum cholesterol concentration on day 56 in swine. AB - Divergent selection for serum cholesterol concentration on d 56 was practiced in a four-breed, composite population for three generations. High and Low lines, representing high and low levels of serum cholesterol, respectively, were each maintained with approximately 10 males and 25 females per generation. Pigs from a contemporary Control line were evaluated only in the last generation. In the last generation, mean serum cholesterol concentration was significantly different among lines (107.1, 85.6, and 65.5 mg/dL for High, Control, and Low lines, respectively). Realized heritability was .31, .33, and .31 for high, low, and divergent selection (SE = .03), respectively. Terminal evaluation indicated that average birth and weaning (28 d of age) weight was lower (P < .05) for Low pigs (1.25 and 6.25 kg, respectively) than for High pigs (1.43 and 7.10 kg, respectively) and was intermediate for Control pigs (1.34 and 6.53 kg, respectively). At 56 d of age, High (15.1 kg) and Control (13.5 kg) pigs were heavier (P < .05) than Low pigs (11.9 kg). However, pigs sampled after 56 d did not differ (P > .05) in average daily gain, 164-d weight, feed consumption, or feed efficiency. Serum cholesterol concentration at 165 d of age was significantly different among lines (110.1, 98.5, and 85.6 mg/dL for High, Control, and Low pigs, respectively), although differences were smaller than at 56 d of age. When slaughtered at approximately 106 kg (188 to 195 d of age), Low pigs had significantly shorter carcasses than High and Control pigs (77.5 vs 78.7 and 78.9 cm, respectively). Low pigs had significantly more fat at the first rib (5.70 vs 5.28 cm) than High pigs. Lines did not differ significantly for fat thickness at the last rib, last lumbar vertebrae or 10th rib, or for longissimus muscle area. At 60 d of gestation, ovulation rate, measured as number of corpora lutea, was lower (P < .05) for High (9.84 eggs) than for Low (11.79 eggs) or Control (11.17 eggs) gilts. Differences in ovulation rate were reflected in smaller but nonsignificant differences in number of fetuses (7.97, 9.00, and 8.55 fetuses for High, Low, and Control, respectively). PMID- 8349503 TI - Energy metabolism of growing pigs after transportation, regrouping, and exposure to new housing conditions as affected by feeding level. AB - An experiment was performed to evaluate alterations of energy metabolism with time in 10 groups of 16 barrows just after transportation. Ten-week-old pigs were fed at once (four groups; LF) or twice (three groups; MF) maintenance level (35 and 75 g.kg-.75.d-1, respectively), or allowed ad libitum access to feed (three groups; HF). The 13.5-d experimental period was divided into two balance periods. Heat production (HP) decreased with time. The changes in HP with time were different among feeding level groups (P < .001); the LF group had the greatest decrease. Metabolizable energy intake remained constant with time for the LF and MF groups and decreased for the HF group. Requirements for maintenance energy and efficiency of ME for growth decreased with time. Feeding level influenced (P < .001) energy retention (ER) during the total experimental period. The LF group had a negative ER (-65 kJ.kg-.75.d-1), whereas in the MF and HF groups positive values for ER were obtained (346 and 757 kJ.kg-.75.d-1, respectively). At all feeding levels, animals had a positive protein gain. The level differed between feeding levels (P < .001). Differences among groups (P < .001) were observed in energy retained as fat. Data from the present experiment show that young pigs are not in a steady state of energy metabolism during the 2 wk after transportation. During this period, the relationship between metabolic rate and feed intake alters with time. PMID- 8349504 TI - Evidence of increasing thermal requirement in young, unadapted calves during 6 to 11 days of age. AB - Changes in thermal demand in restrictively fed, unadapted, young calves were studied during the first days after transportation. Twenty-three 6-d-old Holstein Friesian male calves were assigned to one of four ambient temperature treatments: 5, 9, 13, or 18 degrees C. Calves were fed at a constant level below the maintenance requirement (300 kJ of ME.kg-.75.d-1). After arrival, heat production (HP) and energy and nitrogen balance were measured for each calf for 5.5 d. At ambient temperatures of 5 and 9 degrees C, HP was increased compared with temperatures of 13 and 18 degrees C (P < .001). As a consequence, energy retention was decreased at low ambient temperatures (P < .05). At temperatures of 5 and 9 degrees C, body fat mobilization was increased compared with that at temperatures of 13 and 18 degrees C (P < .001). Energy retained as protein was not affected by ambient temperature. During the experimental period, HP decreased with time. Ambient temperature affected this decrease (P < .001), indicating that the relationship between HP and ambient temperature changed with time. The rate of increase in HP below the lower critical temperature was not affected by time, averaging 9.5 kJ.kg-.75.d-1.C degrees-1. Lower critical temperature, however, increased with time by .89 C degrees/d (P < .05). The changing relation between HP and ambient temperature with time in young, unadapted calves after transportation is thus reflected in an alteration in thermal requirement with time. PMID- 8349506 TI - Tissue-specific activity of pentose cycle oxidative enzymes during feeder lamb development. AB - Relationships between pentose cycle oxidative activity and differential fat growth were evaluated. Rambouillet wether lambs (n = 60) were slaughtered serially at 0, 40, 80, and 120 d on feed (15 lambs/group). Rack dissection and kidney fat weights were collected, and longissimus muscle i.m. fat content was determined. Postmortem longissimus muscle, s.c. fat, intermuscular fat (INT), and kidney fat (KP) samples were assayed in vitro for glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) activity (nanomoles.minute-1.gram of tissue-1), and samples were subjected to electrophoresis (PAGE) to separate tissue-specific isoforms. Allometric coefficients for rack components indicated that s.c. fat was the earliest maturing, slowest-growing depot, INT was the latest-maturing, fastest-growing depot, and i.m. fat was intermediate (P < .05). Kidney fat grew faster than carcass weight and, as carcass weight increased, the growth rate of KP accelerated (P < .05). Enzyme activities increased until 40 d on feed and declined thereafter. Activities differed across tissues and time on feed end points (P < .05). Ratios of G6PDH:6PGDH, reflecting flux through the oxidative phase of the pentose cycle and, therefore, lipogenic activity, suggested growth patterns similar to those indicated by allometric analysis, except in the i.m. fat depot. Development of i.m. fat initially was intermediate to KP and INT, but G6PDH:6PGDH ratios increased with time on feed, suggesting a different regulatory mechanism and maturing pattern. Multiple forms of G6PDH were detected with PAGE, and although polymorphism was not detected, a tissue-specific isoform was isolated for INT fat. PMID- 8349505 TI - Effects of exogenous porcine somatotropin on the carcass composition, hormonal and metabolic profiles, lipogenic capacity, and binding of insulin to erythrocyte receptors of fast- versus slow-growing swine. AB - Twenty barrows were designated as fast-growing (FG) and their littermates designated as slow-growing (SG) based on birth, weaning, and 56-d weight. Half of each group received 70 micrograms of porcine somatotropin (pST)/kg BW daily beginning at 40 kg BW. At 60 and 105 kg BW, blood was collected every .5 h for 12 h beginning 1 h before pST injection, fat biopsies were taken for in vitro lipogenic activity, and insulin erythrocytes were isolated for receptor binding. Swine treated with pST had elevated ADG (.95 vs .88 kg/d; P < .1) and reduced days to slaughter (61 vs 67; P < .1). The pST-treated pigs had less average backfat (2.73 vs 3.96 cm; P < .01), larger longissimus muscle areas (32.3 vs 28.2 cm2; P < .05), and a higher percentage of muscle (56.3 vs 50.3%; P < .01) than control pigs. Exogenous pST increased protein (17.4 vs 13.2%; P < .05) and decreased fat (22.9 vs 37.1%; P < .05). The FG pigs had higher ADG (.98 vs .86 kg/d; P < .01) and required fewer days to slaughter (57 vs 71; P < .01) than SG pigs. Administration of pST increased (P < .01) average pST levels (1.7 vs 14.0 ng/mL) in FG and SG pigs at 60 kg BW. At 105 kg BW, pST was higher (P < .01) in pST-FG than in pST-SG swine (46.0 vs 19.3 ng/mL) but was not different between FG and SG control swine (1.9 vs 1.8 ng/mL). Administration of pST increased concentrations of IGF-I (510.0 vs 160.0 ng/mL) and nonesterified fatty acids (182 vs 109 muEq/L, P < .01) in FG and SG swine. Over sample periods and growth rates, pST reduced (P < .05) CO2 production and lipid synthesis (.345 and 1.85 vs .575 and 2.71 mumol of glucose incorporated.g-1.2 h-1). At 60 kg BW, FG swine had less (P < .01) CO2 production and lipid synthesis (.299 and 1.83 vs .921 and 3.61 mumol.g-1.2 h-1) than did SG swine. Exogenous pST increased (P < .05) binding to insulin erythrocyte receptors (7.25 vs 6.34%). PMID- 8349507 TI - Foodservice industry market profile study: in-plant beef fat trim level survey and cutting yields. AB - Fifty foodservice purveying companies were sampled in 12 U.S. cities evenly distributed across six geographical regions. Beef whole muscle cuts (WMC) and portion control items (PCI) from the primal rib and loin were evaluated for surface fat levels. Fat thicknesses were measured on WMC before and after fabrication, whereas additional PCI were measured for fat trim levels before distribution. The average initial fat thickness was 11.9 mm (174 Short Loin and 180A Strip Loin) and 15.6 mm (184 Top Sirloin Butt); maximum fat thicknesses ranged from 16.2 mm (strip loin) to 22.2 mm (top sirloin butt). After fabrication, average fat thicknesses were 6.2, 5.1, and 4.0 mm for resulting products from the short loin, strip loin, and top sirloin butt, respectively. The average initial fat thickness for the strip loin was greater (P < .05) in Southeast and Northeast regions than in Mountain/Desert, Midwest, and Southwest regions. In contrast, average trimmed fat thicknesses for products from the strip loin and top sirloin butt were lower (P < .05) in the Southeast and Northeast than in all other regions. Average fat trim levels for PCI were 3.0 (1112A Ribeye Roll steak, Lip-On), 5.3 (1173B/1174B T-Bone/Porterhouse steak), 5.0 (1180A Strip Loin steak), and 4.0 mm (1184B Top Sirloin steak). Maximum fat trim levels were 4.4 (IMPS 1112A), 7.4 (IMPS 1173B/1174B), 6.9 (IMPS 1180A), and 5.5 mm (IMPS 1184B). The PCI had average and maximum fat trim levels in compliance with USDA (1988) recommendations for fat trim specifications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349508 TI - Dietary versus postmortem supplementation of vitamin E on pigment and lipid stability in ground beef. AB - Effects of dietary supplementation and postmortem addition of vitamin E on pigment and lipid stability in raw ground beef were examined in this study. Six Holstein steers were fed a control diet for 232 or 252 d and six Holstein steers were supplemented with 1,500 IU of vitamin E per animal daily for 232 or 252 d. Three aliquots of ground beef from each longissimus lumborum were allotted to the following postmortem treatments: no addition (NO), white mineral oil (OIL), and white mineral oil containing sufficient D-alpha-tocopherol to equal the mean difference of alpha-tocopherol concentration between beef from supplemented and control steers (OIL + E). Metmyoglobin percentages and 2-thiobarbituric acid reactive substances values were determined at d 1, 3, 5, 7, and 9 after postmortem treatment. Dietary vitamin E supplementation delayed metmyoglobin increase and highly suppressed lipid oxidation in ground beef during 9 d of display compared with the control. The postmortem addition of vitamin E (OIL + E) was slightly effective in retarding the oxidation of pigment and lipid, especially compared with the OIL treatments. Endogenous vitamin E improved pigment and lipid stability much better than exogenous vitamin E. PMID- 8349509 TI - Intramuscular collagen characteristics of ram, wether, and zeranol-implanted ram lambs. AB - Eighteen spring-born Columbia ram, wether, and zeranol-implanted ram lambs were studied to determine the influence of castration or zeranol implants on intramuscular collagen (IMC) properties and muscle shear force values. Warner Bratzler shear force values for longissimus muscle were greatest for ram lambs, intermediate for implanted rams, and least for wethers (P < .05). Nonreducible collagen crosslink concentration was greater in IMC of rams and implanted rams (P < .05). The IMC from rams compared with that from wethers contained proportionately more Type III than Type I collagen (P < .05); values for implanted rams were intermediate. Heat-soluble muscle collagen concentration was greater for rams and implanted rams than for wethers (P < .05); however, insoluble collagen concentration did not differ by treatment. Muscle collagen concentrations were not different for rams, wethers, or implanted rams. Increased shear force values in rams were associated with elevated collagen crosslink concentration and increased proportion of Type III collagen. Greater concentration of soluble collagen in ram IMC neither diminished nor diluted IMC crosslinking. The proportion of heat-labile collagen in the fractions did not reflect the IMC crosslinking profile for ram and wether lambs. Zeranol implantation modified IMC characteristics of rams such that shear force values and some collagen properties were similar to those of wethers. PMID- 8349510 TI - Enrichment of omega-3 fatty acids in suckling pigs by maternal dietary fish oil supplementation. AB - This study was designed to determine whether substituting menhaden fish oil (FO) for lard (LA) in a practical sow diet was a suitable method for enriching newborn pigs with omega-3 polyunsaturated fatty acids (n-3 PUFA). On d 107 of gestation, 18 crossbred sows were randomly allotted to one of three experimental diets, in which FO was substituted for LA at 0, 3.5, and 7% of the diet. On d 1, 7, 14, and 21 after farrowing samples of milk and serum from the sows and pig serum were collected for fatty acid analysis. The content of n-3 PUFA in the serum of sows fed FO increased six-fold over that in serum of LA-fed sows P < .0001). Feeding FO decreased the levels of arachidonic acid in maternal serum by approximately 50% (P < .0001). Similar changes were reflected in the fatty acid profiles of sow's milk. Pig serum n-3 PUFA levels were elevated over 5- and 10-fold within 24 h of birth in those litters born to sows fed 3.5 and 7% fish oil, respectively. Eicosapentaenoic acid levels in pig serum increased linearly (P < .01) during the first 2 wk postnatally in pigs suckling FO-feds sows and accounted for as much as 12% of the total fatty acids present on d 21. In conclusion, we have demonstrated that feeding FO to sows during late gestation and lactation enriches the newborn pig with n-3 PUFA. PMID- 8349511 TI - Effect of dietary lysine levels formulated by altering the ratio of corn:soybean meal with or without dried whey and L-lysine.HCl in diets for weanling pigs. NCR 42 Committee on Swine Nutrition. AB - A regional cooperative study (NCR-42 Committee) evaluated the efficacy of supplemental dried whey and L-lysine.HCl in a corn-soybean meal-based diet for weanling pigs. The experiment involved five research institutions using a total of 960 crossbred pigs weaned between 3 and 4 wk of age. The experiment was conducted as a randomized, complete block design in 15 replications with a minimum of two replicates per station. Two diets were formulated to contain either .95 or 1.10% lysine by altering the ratio of corn:soybean meal (C-SBM). Two other diets were formulated to the same lysine levels but with 20% dried whey (C-SBM-DW). Supplemental L-lysine.HCl was added to each diet mixture as another variable, increasing the lysine level of each diet by .15%. There were station effects (P < .01) for each trait, but no station x treatment interactions (P > .15). Feed intakes and weight gains were greater (P < .01) for pigs fed diets containing dried whey, and there was a greater response (26 vs 10%) to the C-SBM DW diet that contained 1.10% lysine than to the C-SBM-DW diet at the .95% lysine level. Performance was not improved when L-lysine.HCl was added to either the .95 or 1.10% lysine C-SBM diets, and it elicited a small, but nonsignificant, gain response when it was added to the C-SBM-DW diets. These results suggest that gain and feed performance responses of weanling pigs improved when diets contained dried whey. Lysine was not the limiting factor in either the C-SBM or C-SBM-DW diet formulated to either .95 or 1.10%. Another factor in dried whey was assumed to be responsible for its growth promotion effect. PMID- 8349512 TI - Evaluation of animal protein supplements in diets of early-weaned pigs. AB - Three growth assays were conducted to determine the efficacy of replacing dried skim milk and(or) dried whey in diets of starting pigs with commercially available spray-dried porcine plasma, spray-dried porcine blood, spray-dried bovine plasma, or spray-dried extracted meat protein. In Exp. 1, 236, 24-d-old crossbred pigs were fed diets containing either skim milk and whey or porcine plasma from 0 to 14 d postweaning and whey or porcine plasma from 14 to 28 d. Although pigs fed diets containing porcine plasma had greater ADFI and ADG than those fed milk products from 0 to 7 d, no differences were observed from d 0 to 14 or from 14 to 28 d postweaning. In Exp. 2, 204, 21-d-old pigs were fed corn soybean meal-based diets using the following supplemental protein source combinations: skim milk and whey; skim milk, whey, and casein; porcine plasma, whey, and lactose/starch (10%); porcine plasma and lactose/starch (24.4%); or whey. A common diet (1.25% lysine, 10% whey) was fed from 14 to 35 d postweaning. Pigs fed diets containing porcine plasma consumed more feed and had greater ADG than others (P < .05) from 0 to 14 d and from 0 to 35 d. Both ADG and ADFI were highest when the diet contained 10.3% porcine plasma, 20% whey, and 10% added lactose. Experiment 3 used 150, 21-d-old pigs to compare the inclusion of skim milk, porcine plasma, porcine blood, bovine plasma, or meat extract in diets fed from 0 to 14 d postweaning. A common diet (the same as in Exp. 2) was fed from 14 to 35 d. Pigs fed porcine plasma had greater ADFI (P < .05) from 0 to 14 d than pigs fed other treatments. Also, pigs fed porcine plasma had greater ADG (P < .05) from 0 to 14 d than pigs fed all other diets except porcine blood. Pigs fed porcine blood had the largest ADFI (P < .05) from 14 to 35 d compared with pigs fed other diets. These experiments indicate that porcine plasma is a protein supplement superior to skim milk in diets of starting pigs and that porcine blood has a positive influence on subsequent growth performance. PMID- 8349513 TI - Utilization of medium-chain triglycerides by neonatal pigs: effects of emulsification and dose delivered. AB - Four trials were conducted using 86, 24-h-old pigs to evaluate the utilization of medium-chain triglycerides (MCT). Effects of emulsification and amount of MCT fed were examined. After a 4-h period during which feed was withheld, pigs were force fed MCT (containing 75% octanoate and 25% decanoate), marking time 0 of the experiment. Blood samples were obtained at 1 and 2 h for subsequent medium-chain fatty acid (MCFA) analysis. In Trials 1 (six pigs/treatment) and 2 (four pigs/treatment) the response to three emulsifying agents was compared to a nonemulsified (NE) control. Twenty milliliters of a 30% (vol/vol) emulsion of MCT or 6 mL of NE MCT was administered. Concentrations of MCFA at 1 h in pigs receiving a Tween 80 (polyoxy-ethylene [20] sorbitan monooleate) emulsion were 3- to 19-fold higher than concentrations in animals administered a gum arabic/gum tragacanth emulsion, a lecithin emulsion, or NE MCT. Trials 3 (eight pigs/treatment) and 4 (six pigs/treatment) were conducted to determine the plasma MCFA concentrations resulting from feeding increasing levels of NE (3, 6, 9, or 12 mL of MCT) or emulsified MCT oil (2, 4, 6, or 8 mL in a 30% Tween 80 emulsion). Plasma octanoate concentrations measured at 1 h increased linearly (P < .05) with increasing MCT dosage through 9 mL of NE and 6 mL of emulsified MCT. A transient narcosis was observed in 8 of 12 animals that received 6 or 8 mL of emulsified MCT and was most pronounced 1 to 2 h after feeding, which roughly corresponded to peak plasma MCFA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349514 TI - Emulsification and fatty-acid chain length affect the utilization of medium-chain triglycerides by neonatal pigs. AB - Three experiments were conducted using 52 pigs between 22 and 35 h of birth to determine the effects of emulsification and fatty-acid chain length on utilization of medium-chain triglycerides (MCT). After a 4-h period during which feed was withheld, pigs were force-fed 6 mL of nonemulsified (NE) MCT or 20 mL of a 30% (vol/vol) Tween 80-(polyoxy-ethylene [20] sorbitan monooleate) MCT emulsion, marking time 0, and serial blood samples were drawn throughout 8 h for analysis of medium-chain fatty acid (MCFA) concentrations by HPLC. In Exp. 1, pigs received either NE or emulsified Tri-C4, -C5, -C6, or -C7. The emulsified treatments were discontinued due to deaths caused by coma resulting from high concentrations (up to 12 mM) of plasma MCFA. Concentrations in pigs fed emulsified MCT were 2.5-fold higher than those in pigs fed NE MCT. In pigs fed NE MCT, concentrations of even-chain-length MCFA were higher than those of odd-chain length MCFA (P < .001), with a tendency for C6 to be higher than C4 (P < .1). In Exp. 2 and 3, pigs received an equimolar mixture of MCT in either emulsified or NE form. In Exp. 2, the mixture contained Tri-C4 through Tri-C7; whereas, in Exp. 3 the mixture contained Tri-C4, -C6, -C8, and -C10. A three-way interaction (emulsion x fatty acid x sample time; P < .05) was observed in both experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349515 TI - Effects of the beta-adrenergic agonist clenbuterol in cows: lipid metabolism, milk production, pharmacokinetics, and residues. AB - The effects of the beta-adrenergic agonist clenbuterol on lipid metabolism, milk production, pharmacokinetics, and residues were studied in six lactating Brown Swiss cows. Four of these were treated with the growth-promoting dose of 5 micrograms of clenbuterol/kg of BW, mixed within the concentrate, and administered twice a day for 3 wk. The remaining two cows served as controls. All animals were in their third phase of lactation and were fed diets containing corn silage, hay, and concentrate according to individual milk production level and body weight. Milk and blood samples were collected for analysis following a rigid time schedule. Milk production and milk contents (triglycerides, protein, and lactose) were quantitatively identical in both treated and control animals, whereas significant qualitative changes occurred in the fatty acid composition of milk lipids in clenbuterol-treated animals. Compared with the controls, the relative amount (percentage of total fatty acids) of unsaturated fatty acids, particularly oleic acid (cis-delta 9-octadecaonate, 18:1), increased considerably with a simultaneous decrease of the transition chain length fatty acids (lauric acid [12:0] and myristic acid [14:0]). Plasma glucose and FFA concentrations were elevated. Concentrations of insulin-like growth factor I remained unchanged. We conclude that the physiological effect of clenbuterol is limited to the repartitioning effect in body composition, and that milk production is affected only slightly by clenbuterol. An immediate increase of clenbuterol concentrations in plasma (3.4 +/- 2.0 ng/mL) and milk (10.8 +/- 4.7 ng/mL) could be observed at the commencement of treatment. Clenbuterol concentration peaked after 10 d and remained constant until the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349516 TI - Effects of lactation on fetal survival and development in rabbit does mated shortly after parturition. AB - Primiparous rabbit does were mated within 12 h after parturition (d 0). They were immediately weaned (Group W; n = 31) or allowed to suckle 10 young rabbits (Group L; n = 32). Blood samples were collected at d 0, 7, 17, and 28. Feed intake and live weight were measured weekly and pregnant does (Group W, n = 24; Group L = 25) were slaughtered at d 28. Feed intake was 78% higher in L than in W females throughout gestation (P < .001). However, L females lost weight during the second half of gestation (-243 +/- 25 g) compared with W females, which gained weight (246 +/- 20 g). The weights of carcass, skin, and adipose tissues were severely reduced at d 28 in the L group (P < .01). Ovulation rate (11.0 +/- .3 corpora lutea) and early embryonic mortality (< d 15) were similar in both groups (12.3 +/- 2%), whereas late embryonic mortality (> or = d 15) was higher in L than in W does (13.9 +/- 3 vs 3.9 +/- 1%; P < .01). Fetal weight was reduced by nearly 20% in L compared with W females (P < .01). Plasma concentrations of progesterone were lower in L than in W females at d 7 and 17 (P < .001), whereas concentrations of estradiol were similar in both groups throughout gestation. These results indicate that fetal survival and development can be impaired in lactating females. PMID- 8349518 TI - Influence of initial length of uterus per embryo and gestation stage on prenatal survival, development, and sex ratio in the pig. AB - The effects of uterine length per embryo and stage of gestation on prenatal survival, development, and sex ratio were determined by systematically restricting embryos to 5, 10, 15, 20, 25, 30, 35, 40, 45, or > 50 cm of initial uterine length per potential embryo and examining the reproductive tracts at d 17, 23, 29, 35, or 41 of gestation. At d 3 the mean length of a uterine horn was 169 +/- 35 cm, with a range of 80 to 255 cm. The mean total number of corpora lutea (CL) was 12.4 +/- 2.34. Ovulation rate tended to be correlated with the length of uterine horns (r = .38; P > .1). Prenatal survival was highly correlated with initial assigned uterine space from 5 to 25 cm/CL (r = .95; P < .05). Prenatal survival was not affected by space (r = .53; P < .1) when space was > 25 cm/CL. In all groups, regardless of space available, some prenatal loss occurred before d 17. In sections with < 25 cm/CL, a second loss took place between d 29 and 35. Before d 35, there was no significant effect of restriction on either fetal length or weight, but after d 35, fetuses from sections with > 25 cm/CL were longer and heavier than those from sections with less space (P < .05). Greater uterine space was occupied by larger fetuses (P < .05). Male fetuses occupied more uterine space than female fetuses did in both crowded and roomy sections (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349517 TI - Metabolic and endocrine changes associated with undernutrition in the peripubertal gilt. AB - The effect of feed restriction on circulating metabolites and metabolic and gonadotropic hormones was determined in Large White gilts. From 25 kg BW and 80 d of age, control gilts (CTRL, n = 10) were fed close to ad libitum intake, whereas restricted-fed gilts (REST, n = 10) were offered approximately 50% of the CTRL diet. Estrus was detected with a mature boar. Serial blood samples were collected at approximately 160 and 210 d of age from 0800 to 2000. A meal was supplied at 0900, and an i.v. injection of GnRH (80 ng/kg BW) was given at 1600. The gilts were slaughtered at 220 d of age. No REST and four CTRL gilts exhibited their first estrus between the two series of blood samplings. Feed intake, daily gain, and fat content of the carcass were reduced by 50% in REST gilts (P < .001). Preprandial concentrations of free fatty acids were significantly lower in CTRL gilts at 210 d of age than at 160 d and than in REST gilts at both ages. Within the CTRL group, concentrations were lower (P < .05) at both ages in gilts pubertal before 210 d than in others. After the meal, plasma insulin and urea increased in all gilts, whereas glucose increased and free fatty acids decreased in all except the 210-d CTRL gilts. The afternoon concentration of cortisol was slightly higher (P = .09) in REST than in CTRL gilts. The number of pulses and mean and interpulse concentrations of growth hormone did not show any clear variation with feed level and age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349519 TI - The effect of thiopentone-sodium anesthesia and surgery, relocation, grouping, and hydrocortisone treatment on the blood levels of cortisol, corticosteroid binding globulin, and catecholamines in pigs. AB - Eight crossbred, ovariectomized gilts (Swedish Landrace x Swedish Yorkshire x Hampshire), with a mean age of 7.5 mo, were studied during anesthesia and surgery, control-sampling, relocation, and grouping during a period of 3 wk. Acute treatment with a hydrocortisone injection (5 mg, i.v.) was also given. Blood samples were taken frequently (every 10 min) during the intensive part of the experimental days. The blood samples were analyzed for catecholamines (CA), adrenaline (A) and noradrenaline (NA), cortisol, and corticosteroid-binding globulin (CBG). The surgical period with anesthesia and surgery showed significant effects on CA, cortisol, and CBG. The A level increased immediately after the surgery. A biphasic increase in the cortisol level was observed on the day of surgery; the greatest increase was seen when the animals had regained consciousness after surgery but still were drowsy and staggering. The CBG level decreased on the day after the surgery. The study showed that the levels of the analyzed substances were back to normal 2 d after surgery. During relocation and grouping there was a short, significant increase in CA and cortisol levels, whereas the CBG level was not affected. Treatment with hydrocortisone significantly increased the cortisol level, but no change was seen in plasma CA or CBG levels. In conclusion, anesthesia and surgery induced significant effects on the levels of CA, cortisol, and CBG in gilts and the animals needed 2 d to recover before regaining their normal condition. During relocation and a limited grouping period, the significant increases in CA and cortisol levels were of short duration and CBG did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349520 TI - Stimulation of development of in vitro-matured and in vitro-fertilized bovine embryos by platelets. AB - In vitro-fertilized bovine embryos were incubated in Menezo's B2 medium (MB2) supplemented with 2 mg/mL of BSA. In Exp. 1, eight-cell stage embryos were allotted to one of the following groups: control medium (MB2), MB2 with 20 ng/mL of platelet-activating factor (PAF), 1 x 10(7) bovine blood platelets (Platelets), oviductal cells (BOEC), BOEC and 20 ng/mL of PAF (BOEC+PAF), or BOEC and 1 x 10(7) platelets (BOEC+Platelets). In Exp. 2, eight-cell embryos were allotted to one of the following groups: control medium (MB2), MB2 with 1 x 10(7) platelets (Platelets), 1 x 10(7) platelets and 10 micrograms/mL of platelet derived growth factor antibody (Platelets+anti-PDGF), 1 x 10(7) platelets and 1 microgram/mL of indomethacin (Platelets+Indomethacin), or 1 x 10(7) platelets and 3 micrograms/mL of mianserin (Platelets+Mianserin). Embryos were incubated at 39 degrees C in 5% CO2 in groups of five until 8 d after in vitro fertilization (IVF). In Exp. 1, Platelets stimulated embryo development to the morula, blastocyst, and expanded blastocyst stages. Embryo development was greatest in the BOEC+Platelets group on d 7 and 8 after IVF. Only embryos incubated in the BOEC+Platelets treatment group reached the hatched blastocyst stage on d 8. In Exp. 2, embryos incubated in the Platelets treatment group had the greatest (P < .05) proportion develop beyond the eight-cell stage. Embryos incubated in the Platelets + anti-PDGF group had less (P < .05) development beyond the eight-cell stage and to the morula stage. These results indicate that the stimulatory effects of PDGF on bovine embryo development may be derived from both the oviductal epithelium and platelets. PMID- 8349521 TI - Assessment of protein quality in heat-treated soybean products using the growth responses of lambs and calves and a nylon bag-rooster assay. AB - Three studies were conducted to evaluate N and amino acid (AA) availability from processed soybean (SB) products. In Exp. 1 and 2, treatments consisted of corn cottonseed hull basal diets plus SB products including SB meal (SBM); ground, raw SB (RSB); or extruded SB (ESB). In Exp. 1, 15 Suffolk (28.6 kg) and 15 Louisiana native breed (16.3 kg) ewe lambs were used in a 35-d growth trial. Although breed affected (P < .10) DMI and ADG of lambs, the diets did not (P > .10). In Exp. 2, 12 Suffolk wether lambs (34.0 kg) were used in a 3 x 3 multiple-square Latin square design N metabolism trial. Lambs fed RSB tended (P = .13) to retain more N than those fed ESB, but N retained by lambs fed RSB and ESB was similar (P > .10) to that of lambs fed SBM. In Exp. 3, four crossbred steer calves (240 kg) were used in a 4 x 4 Latin square design N metabolism trial with the above treatments plus heat-damaged SB (HDSB). Calves fed RSB and ESB retained similar (P > .10) amounts of N. Compared with calves fed RSB and ESB, calves fed SBM retained more (P < .10) N. Calves fed HDSB retained less (P < .10) N than those fed other diets. The individual SB products and the total mixed diets used in Exp. 3 were incubated intraruminally in nylon bags and the residual DM recovered and precision-fed to cecectomized roosters to estimate its intestinal AA digestibility. Digestibility of residual AA seemed to be relatively uniform across AA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349522 TI - Combined analysis of tall fescue steer grazing studies in the Eastern United States. AB - The mixed-models procedure (MMP) was used to analyze pooled data sets from 12 independent studies conducted during the last 13 yr at nine locations in seven states to provide combined estimates of daily gains by beef steers (Bos taurus) grazing tall fescue (Festuca arundinacea Schreb.) pastures free of (E-) or infested (E+) at different levels with the endophytic fungus Acremonium coenophialum. Treatments included low-infestation (< or = 5% E+), moderate infestation (> or = 20 to < or = 35% E+), and high-infestation (> or = 50 to < or = 97% E+) tall fescue pastures, and, in tall fescue-clover (Trifolium spp.) mixtures, pastures at the same E+ levels with approximately 25 and 10% clover in spring and summer stands, respectively. Spring, summer, and combined spring+summer data were analyzed separately. The MMP permitted estimation of the fixed effects of treatments over a broad inference space of future years and different tall fescue pastures over a wide geographic range; detected relationships that had not been apparent in the individual studies, such as the interactions between clover presence and E+ infestation levels; and provided a more coherent body of information than did the results obtained from each discrete study. Logistical and financial constraints that force undesirable compromises in the conduct of future grazing and other expensive or time consuming research may be avoided by using MMP within the context of cooperative projects. PMID- 8349523 TI - Maintenance requirements in metabolizable energy of adult, nonpregnant, nonlactating Charolais cows. AB - The objective of this study was to determine the maintenance requirements in metabolizable energy (MEm) of adult, nonlactating, nonpregnant Charolais cows. A feeding trial was conducted using 12 cows fed at one of two feeding levels (75 [L] and 113 [H] kcal of ME.kg BW-.75.d-1) for 116 d. Body composition was estimated from subcutaneous adipocyte diameter. Body weight changes averaged -468 and +46 g/d, respectively. Diet DM digestibility averaged .496. The L cows spent less time eating and ruminating but had other behavioral characteristics similar to those of H cows. Estimates of MEm were calculated from BW or body composition changes and amounted to 109 and 124 kcal of ME.kg BW-.75.d-1, respectively. Heat production (HP) was then measured over 67 d in a second trial on two L and two H cows from the feeding trial and planes of feeding were switched after 14 d. Estimates of MEm varied from 112 to 105 kcal.kg BW-.75.d-1. Within animal, day-to day variations in heat production were high (4.6% on average) and prevented the detection of any precise changes of HP with time on treatment. None of the trials showed any significant effect of level of feeding on MEm. PMID- 8349524 TI - Regulation of fatty acid synthase gene expression: an approach for reducing fat accumulation. AB - Fatty acid synthase (FAS) catalyzes the last step in the fatty acid biosynthetic pathway. The tissue concentration of FAS, which is affected by a number of hormonal and dietary factors, is a key determinant for the maximal capacity of a tissue to synthesize fatty acids by the de novo pathway. The complete nucleotide sequence of the avian and rat FAS transcripts has been cloned. In addition, a 1.5 kb cDNA that represents the thioesterase domain of the pig FAS protein plus the entire 3'-untranslated region of the transcript was isolated from a porcine liver cDNA library. Using these FAS cDNA tools, FAS mRNA transcripts have been found in most tissues, including adipose, liver, lung, brain, kidney, and small intestine. Moreover, the abundance of FAS mRNA in a tissue determines the rate of FAS protein synthesis, and ultimately the tissue content of FAS protein. In the liver, the rate of FAS gene transcription dictates the level of FAS mRNA, whereas the FAS mRNA content of adipose tissue seems to be determined by factors that affect gene transcription and mRNA stability. Adaptive changes in the abundance of FAS mRNA seem to occur primarily in hepatic and adipose tissues, whereas FAS expression in other tissue types is resistant to nutritional and hormonal manipulations. This review presents the concept that the tissue-specific adaptation in FAS gene expression can be exploited to develop a tissue-specific inhibitor of FAS gene expression and, hence, reduce the tissue capacity for fat accretion through the de novo biosynthetic pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349525 TI - Improved cloning vectors and transformation procedure for Lactococcus lactis. AB - Four shuttle vectors (pMIG 1, 2, 2H and 3) have been constructed based on the broad host-range plasmid pCK1. All the pMIG vectors possess a multiple cloning site containing 12 or more unique restriction enzyme sites, and are stably maintained at either high or low copy number in Lactococcus lactis and in Escherichia coli. By cloning the E. coli pUC replicon into one of these vectors a plasmid was constructed which can replicate to high copy number in recA strains of E. coli. The broad host-range of the pCK1 replicon may enable these cloning vectors to be used in a number of Gram-positive bacteria. One of these vectors was used to optimize an electroporation procedure for transformation of a commonly used plasmid-cured strain MG1363 of L. lactis which routinely yielded 1 x 10(7) to 5 x 10(7) transformants micrograms-1 supercoiled DNA using stored, snap-frozen cells. This transformation efficiency was obtained by growing the cells in medium containing the cell wall weakening agent glycine, to an upper limit of 2.5% w/v. Although growth of L. lactis strain MG1363 was inhibited by the use of 0.5 mol l-1 sucrose as an osmotic stabilizer, the presence of sucrose in the electroporation buffer was critical for high transformation efficiency. Other variables which were tested for their effect on the efficiency of transformation were cell concentration, DNA concentration, pulse time and field strength. These results provide a model procedure which can be followed to optimize conditions for the genetic transformation of various strains of L. lactis. PMID- 8349526 TI - Potential problems in the use of oligonucleotide probes for staphylococcal enterotoxin genes. AB - Oligonucleotide probes unique to the five major enterotoxin genes of Staphylococcus aureus were synthesized and used to detect DNA sequences homologous to these genes in 27 non-clinical isolates of Staph. aureus isolated from nasal swabs of 74 healthy human volunteers. Genomic DNA from all 27 isolates reacted with at least one of the probes. In a phenotypic assay for toxin production by a reverse passive latex agglutination test however, only 15 of the 27 isolates produced enterotoxin in culture. The results raise the possibility that a number of Staph. aureus isolates harbour DNA sequences that are apparently silent or mutant copies of the enterotoxin genes. This complicates the identification of enterotoxin producers by tests which depend on oligonucleotide or DNA hybridization. PMID- 8349527 TI - A note on lactobacilli and beta-glucuronidase activity in the intestinal contents of mice. AB - A comparison was made of caecal beta-glucuronidase activity in the caecal contents of mice with or without lactobacilli as members of the normal microflora. Male mice that did not have lactobacilli as intestinal inhabitants had approximately 52% more caecal beta-glucuronidase activity than their female counterparts. Colonization of male mice by lactobacilli reduced the beta glucuronidase activity to that of female mice. PMID- 8349528 TI - The effects of transgalactosylated oligosaccharides on gut flora metabolism in rats associated with a human faecal microflora. AB - The effect on various caecal bacteria and their metabolic activities of feeding diet containing transgalactosylated oligosaccharides (TOS) with or without Bifidobacterium breve (administered in the drinking water) was investigated in rats colonized with a human faecal microflora. TOS (5% w/w in diet) or TOS plus B. breve, given for 4 weeks, induced increases in caecal concentration of total anaerobic bacteria, lactobacilli and bifidobacteria, and decreases in numbers of enterobacteria. Caecal pH was significantly reduced by feeding TOS, as were the activities of beta-glucuronidase and nitrate reductase. In contrast, beta glucosidase activity was increased in TOS-fed rats. Dietary TOS was also associated with decreased conversion, by caecal contents, of the dietary carcinogen 2-amino-3-methyl-3H-imidazo[4,5-f] quinoline (IQ) to its genotoxic 7 hydroxy derivative. PMID- 8349529 TI - Prokaryote envelope diversity. PMID- 8349530 TI - Composition of the envelope layers of Saccharomyces cerevisiae in relation to flocculation and ethanol tolerance. PMID- 8349531 TI - Cell envelope diversity and dynamics in yeasts and filamentous fungi. PMID- 8349532 TI - On mechanisms of oral microbial adhesion. PMID- 8349533 TI - Current trends and future prospects in prokaryotic envelope research: a microscopist's view. PMID- 8349534 TI - Envelope structure and the development of new vaccines. PMID- 8349535 TI - Formation and dispersal of bacterial biofilms in vivo and in situ. PMID- 8349536 TI - Coaggregation of human oral bacteria: potential role in the accretion of dental plaque. PMID- 8349537 TI - Sensitivity of biofilms to antimicrobial agents. PMID- 8349538 TI - LexA cleavage and other self-processing reactions. PMID- 8349539 TI - Coordinated regulation of amino sugar-synthesizing and -degrading enzymes in Escherichia coli K-12. AB - The intracellular concentration of the enzyme glucosamine-6-phosphate synthase, encoded by the gene glmS in Escherichia coli, is repressed about threefold by growth on the amino sugars glucosamine and N-acetylglucosamine. This regulation occurs at the level of glmS transcription. It is not due just to the presence of intracellular amino sugar phosphates, because mutations which derepress the genes of the nag regulon (coding for proteins involved in the uptake and metabolism of N-acetylglucosamine) also repress the expression of glmS in the absence of exogenous amino sugars. PMID- 8349540 TI - Minimum domain of the Shiga toxin A subunit required for enzymatic activity. AB - The minimum sequence of the enzymatic (A) subunit of Shiga toxin (STX) required for activity was investigated by introducing N-terminal and C-terminal deletions in the molecule. Enzymatic activity was assessed by using an in vitro translation system. A 253-amino-acid STX A polypeptide, which is recognized as the enzymatically active portion of the 293-amino-acid A subunit, expressed less than wild-type levels of activity. In addition, alteration of the proposed nicking site between Ala-253 and Ser-254 by site-directed mutagenesis apparently prevented proteolytic processing but had no effect on the enzymatic activity of the molecule. Therefore, deletion analysis was used to identify amino acid residue 271 as the C terminus of the enzymatically active portion of the STX A subunit. STX A polypeptides with N-terminal and C-terminal deletions were released into the periplasmic space of Escherichia coli by fusion to the signal peptide and the first 22 amino acids of Shiga-like toxin type II, a member of the STX family. Although these fusion proteins expressed less than wild-type levels of enzymatic activity, they confirmed the previous finding that Tyr-77 is an active-site residue. Therefore, the minimum domain of the A polypeptide which was required for the expression of enzymatic activity was defined as StxA residues 75 to 268. PMID- 8349541 TI - Isolation and characterization of an Escherichia coli strain with a high frequency of C-to-T mutations at 5-methylcytosines. AB - We used a genetic selection system to isolate a strain of Escherichia coli with a high frequency of C-to-T transition mutations at the second C of the sequence CCAGG. Cytosines in other sequences do not mutate to thymine at a high frequency in this strain, and the frequencies of other base substitution mutations are not increased to the same extent. The gene responsible for the mutator phenotype has been mapped to 43 min on the E. coli chromosome. Several lines of evidence indicate that this gene is distinct from the very short patch repair gene vsr. PMID- 8349542 TI - An oxygen-dependent coproporphyrinogen oxidase encoded by the hemF gene of Salmonella typhimurium. AB - The 8th step in the 10-step heme biosynthetic pathway of Salmonella typhimurium is the oxidation of coproporphyrinogen III to protoporphyrinogen IX. On the basis of genetic studies, we have suggested that this reaction may be catalyzed by either of two different enzymes, an oxygen-dependent one encoded by hemF or an oxygen-independent enzyme encoded by hemN. Here, we report the cloning of the S. typhimurium hemF gene and its DNA sequence. The predicted amino acid sequence of the HemF protein is 44% identical to that of the coproporphyrinogen oxidase encoded by the yeast HEM13 gene. The wild-type S. typhimurium strain LT-2 produces an oxygen-dependent coproporphyrinogen oxidase activity detectable in crude extracts, which is not found in hemF mutants and is overproduced in strains carrying the hemF gene on a multicopy plasmid. the hemF gene is the second gene in an operon with an upstream gene with an unknown function, whose amino acid sequence suggests a relation to amidases involved in cell wall synthesis or remodeling. The upstream gene and hemF are cotranscribed from a promoter which was mapped by primer extension. A weaker, hemF-specific promoter is inferred from the behavior of an omega-Cm insertion mutation in the upstream gene. Although this insertion decreases expression of beta-galactosidase about 7.5-fold when placed upstream of a hemF-lacZ operon fusion, it still allows sufficient HemF expression from an otherwise wild-type construct to confer a Hem+ phenotype. The hemF operon is transcribed clockwise with respect to the genetic map. PMID- 8349543 TI - Patterns of gene expression in Bacillus subtilis colonies. AB - Bacillus subtilis 5:7, a derivative of macrofiber-producing strain FJ7, carries the lacZ reporter gene within Tn917 at an unknown location in the host genome. Expression of the host gene carrying lacZ within colonies of 5:7 was observed by examining growth under different conditions in the presence of 5-bromo-4-chloro-3 indolyl-beta-D-galactopyranoside (X-Gal). At a high plating density small colonies arose that expressed the host gene early and throughout the colony, whereas at a low density large colonies were produced that expressed the host gene late in development and only in cells forming a ring pattern close to the colony periphery. A highly regulated spatial and temporal gene expression pattern was observed in growth from cross-streaks, suggesting that gene expression is responsive to concentration gradient fields established by neighboring growth. Colonies cultured on agar blocks revealed that expression was governed by depletion of a medium component and also by the geometry of the substrate upon which the colonies grew. At least three factors influenced the control of expression: (i) the concentration of a diffusible component of the medium exhausted by cell growth, (ii) a spatial-temporal factor related to growth within the colony, and (iii) the geometry of the growth substrate. PMID- 8349544 TI - Interplay between the membrane-associated UhpB and UhpC regulatory proteins. AB - Expression of the Escherichia coli uhpT gene, encoding the sugar phosphate transport protein, is induced by extracellular glucose-6-phosphate and requires the function of the uhpABC regulatory genes. The UhpA and UhpB proteins are related to the response-regulator and sensor-kinase proteins of two-component regulatory systems, whereas the UhpC protein is related to UhpT and homologous transport proteins. To investigate the role of segments of the membrane associated UhpB and UhpC regulatory proteins, a series of mutations were constructed in vitro by insertion of a 12- or 24-bp oligonucleotide linker at 44 sites within the uhpABCT locus. The effect of these mutations on regulation of a uhpT-lacZ transcriptional reporter was assayed with the mutated uhp alleles in single copy on the chromosome. All but one of the insertions in uhpA or uhpT were inactive for transcription activation or transport, respectively. In contrast, about half of the insertions in uhpB and uhpC retained Uhp expression, and insertions at four sites in uhpB and at one site in uhpC conferred high-level constitutive expression. The constitutive mutants in UhpB resulted from insertions in the nonpolar amino-terminal half of the protein, and all insertions in that half of UhpB affected Uhp expression in some manner, which suggests that the transmembrane segments of UhpB might negatively regulate the kinase activity of the carboxyl portion. The constitutive behavior of all but one of these uhpB alleles was dependent on the presence of active forms of both UhpA and UhpC, which suggests that UhpB and UhpC act jointly as a complex in the signaling process. PMID- 8349545 TI - Nucleotide sequence and characterization of the traABCD region of IncI1 plasmid R64. AB - A 3.6-kb BglII-SmaI segment of the transfer region of IncI1 plasmid R64drd-11 was sequenced and characterized. Analysis of the DNA sequence indicated the presence of four genes, traA, traB, traC, and traD, in this region. The expression of the traB, traC, and traD genes was examined by maxicell experiments and that of the traA gene was examined by constructing the traA-lacZ fusion gene. The introduction of frameshift mutations into the four genes indicated that the traB and traC genes are essential for conjugal transfer in liquid medium and on a solid surface. Both were also required for the formation of the thin pilus, which is the receptor for phages I alpha and PR64FS. Upstream of the traA gene, a promoter sequence for sigma 70 of E. coli RNA polymerase was identified by S1 nuclease mapping and primer extension experiments. PMID- 8349546 TI - OmpF assembly mutants of Escherichia coli K-12: isolation, characterization, and suppressor analysis. AB - This paper describes a novel genetic method used to isolate mutations that alter proper assembly of OmpF in the outer membrane. The thermolabile nature of assembly intermediates allowed selection of temperature-sensitive mutations within the ompF gene. A variant allele of ompF (ompF-Dex) was used because it provided a convenient selectable phenotype (Dex+). Assembly mutants were isolated in two steps. First, amber mutations were obtained that mapped in ompF-Dex. This resulted in a Dex- phenotype. Starting with these Dex- strains, Dex+ revertants were isolated. Mutants that displayed a temperature-sensitive Dex+ phenotype were further characterized. Three such mutants possessed a single substitution within ompF that reverted the nonsense codon to a sense codon which replaced W214 with either an E or Q and Y231 with a Q residue in the mature OmpF protein. All three mutant OmpF proteins showed an assembly defect. This defect led to a substantial reduction in the amount of stable OmpF trimers with the concomitant increase of a high-molecular-weight form of OmpF which migrated at the top of the gel. Suppressor mutations were sought that corrected the assembly defect of OmpF. These extragenic suppressor mutations were mapped at 45 min on the Escherichia coli chromosome. The suppressor mutations displayed no allele specificity and were recessive to the wild-type allele. In the presence of a suppressor, mutant stable trimers appeared in an almost normal manner. The appearance of stable trimers concurred with a substantial loss of the high-molecular-weight OmpF species. At this stage, it is not clear whether the high-molecular-weight species of OmpF is a normal assembly intermediate or a dead-end assembly product. The results presented in this study raise the intriguing possibility of a chaperone like activity for the wild-type suppressor gene product. PMID- 8349547 TI - Complementation analysis and regulation of CO2 fixation gene expression in a ribulose 1,5-bisphosphate carboxylase-oxygenase deletion strain of Rhodospirillum rubrum. AB - A ribulose 1,5-bisphosphate carboxylase-oxygenase (RubisCO) deletion strain of Rhodospirillum rubrum that was incapable of photolithoautotrophic growth was constructed. Photoheterotrophic growth, however, was possible for the R. rubrum RubisCO deletion strain when oxidized carbon compounds such as malate were supplied. The R. rubrum RubisCO-deficient strain was not complemented to photolithoautotrophic growth by various R. rubrum DNA fragments that contain the gene encoding RubisCO, cbbM. When the R. rubrum cbbM deletion strain harbored plasmids containing R. rubrum DNA inserts with at least 2.0 kb preceding the translational start site of the cbbM gene, RubisCO activity and RubisCO antigen were detected. Lack of RubisCO expression was therefore not the cause for the failure to complement the cbbM mutant strain. Interestingly, DNA fragments encoding either of two complete Calvin-Benson-Bassham CO2- fixation (cbb) gene operons from Rhodobacter sphaeroides were able to complement the R. rubrum RubisCO deletion strain to photolithoautotrophic growth. The same R. rubrum DNA fragments that failed to complement the R. rubrum cbbM deletion strain successfully complemented the RubisCO deletion strain of R. sphaeroides, pointing to distinct differences in the regulation of metabolism and the genetics of photolithoautotrophic growth in these two organisms. A number of cbb genes were identified by nucleotide sequence analysis of the region upstream of cbbM. Included among these was an open reading frame encoding a cbbR gene showing a high degree of sequence similarity to known lysR-type CO2 fixation transcriptional activator genes. The placement and orientation of the cbbR transcriptional regulator gene in R. rubrum are unique. PMID- 8349549 TI - Staphylococcus aureus has clustered tRNA genes. AB - The polymerase chain reaction (PCR) was used to detect large tRNA gene clusters in Bacillus subtilis, Bacillus badius, Bacillus megaterium, Lactobacillus brevis, Lactobacillus casei, and Staphylococcus aureus. The primers were based on conserved sequences of known gram-positive bacterial tRNA(Arg) and tRNA(Phe) genes. This PCR procedure detected an unusually large tRNA gene cluster in S. aureus. PCR-generated probes were used to identify a 4.5-kb EcoRI fragment that contained 27 tRNA genes immediately 3' to an rRNA operon. Some of these 27 tRNA genes are very similar, but only 1 is exactly repeated in the cluster. The 5' end of this cluster has a gene order similar to that found in the 9- and 21-tRNA gene clusters of B. subtilis. The 3' end of this S. aureus cluster exhibits more similarity to the 16-tRNA gene cluster of B. subtilis. The 24th, 25th, and 26th tRNA genes of this S. aureus tRNA gene cluster code for three similar, unusual Gly-tRNAs that may be used in the synthesis of the peptidoglycan in the cell wall but not in protein synthesis. Southern analysis of restriction digests of S. aureus DNA indicate that there are five to six rRNA operons in this bacterium's genome and that most or all may have large tRNA gene clusters at the 3' end. PMID- 8349548 TI - kil-kor regulon of promiscuous plasmid RK2: structure, products, and regulation of two operons that constitute the kilE locus. AB - The kil-kor regulon of IncP plasmid RK2 is a complex regulatory network that includes genes for replication and conjugal transfer, as well as for several potentially host-lethal proteins encoded by the kilA, kilB, and kilC loci. While kilB is known to be involved in conjugal transfer, the functions of kilA and kilC are unknown. The coregulation of kilA and kilC with replication and transfer genes indicates a possible role in the maintenance or broad host range of RK2. In this work, we found that a fourth kil locus, designated kilE, is located in the kb 2.4 to 4.5 region of RK2 and is regulated as part of the kil-kor regulon. The cloned kilE locus cannot be maintained in Escherichia coli host cells, unless korA or korC is also present in trans to control its expression. The nucleotide sequence of the kilE region revealed two potential multicistronic operons. The kleA operon consists of two genes, kleA and kleB, predicted to encode polypeptide products with molecular masses of 8.7 and 7.6 kDa, respectively. The kleC operon contains four genes, kleC, kleD, kleE, and kleF, with predicted products of 9.2, 8.0, 12.2, and 11.3 kDa, respectively. To identify the polypeptide products, each gene was cloned downstream of the phage T7 phi 10 promoter and expressed in vivo in the presence of T7 RNA polymerase. A polypeptide product of the expected size was observed for all six kle genes. In addition, kleF expressed a second polypeptide of 6 kDa that most likely results from the use of a predicted internal translational start site. The kleA and kleC genes are each preceded by sequences resembling strong sigma 70 promoters. Primer extension analysis revealed that the putative kleA and kleC promoters are functional in E. coli and that transcription is initiated at the expected nucleotides. The abundance of transcripts initiated in vivo from both the kleA and kleC promoters was reduced in cells containing korA or korC. When korA and korC were present together, they appeared to act synergistically in reducing the level of transcripts from both promoters. The kleA and kleC promoter regions are highly homologous and contain two palindromic sequences (A and C) that are the predicted targets for KorA and KorC proteins. DNA binding studies showed that protein extracts from korA containing E. coli cells specifically retarded the electrophoretic mobility of DNA fragments containing palindrome A. Extracts from korC-containing cells altered the mobility of DNA fragments containing palindrome C. These results show that KorA and KorC both act as repressors of the kleAand kleC promoters. In the absence of korA and korC, expression of the cloned kleA operon was lethal to E.coli cells, whereas the cloned kleC operon gave rise to slowly growing, unhealthy colonies. Both phenotypes depended on at least one structural gene in each operon, suggesting that the operons encode genes whose products interact with critical host functions required for normal growth and viability. Thus, the kilA, kilC, and kilE loci of RK2 constitute a cluster of at least 10 genes that are coregulated with the plasmid replication initiator and the conjugal transfer system. Their potential toxicity to the host cell indicates that RK2 is able to establish a variety of intimate plasmid-host interactions that may be important to its survival in nature. PMID- 8349551 TI - Physical genome map of the unicellular cyanobacterium Synechococcus sp. strain PCC 7002. AB - A physical restriction map of the genome of the cyanobacterium Synechococcus sp. strain PCC 7002 was assembled from AscI, NotI, SalI, and SfiI digests of intact genomic DNA separated on a contour-clamped homogeneous electric field pulsed field gel electrophoresis system. An average genome size of 2.7 x 10(6) bp was calculated from 21 NotI, 37 SalI, or 27 SfiI fragments obtained by the digestions. The genomic map was assembled by using three different strategies: linking clone analysis, pulsed-field fragment hybridization, and individual clone hybridization to singly and doubly restriction-digested large DNA fragments. The relative positions of 21 genes or operons were determined, and these data suggest that the gene order is not highly conserved between Synechococcus sp. strain PCC 7002 and Anabaena sp. strain PCC 7120. PMID- 8349550 TI - Purification and characterization of a primary-secondary alcohol dehydrogenase from two strains of Clostridium beijerinckii. AB - Two primary alcohols (1-butanol and ethanol) are major fermentation products of several clostridial species. In addition to these two alcohols, the secondary alcohol 2-propanol is produced to a concentration of about 100 mM by some strains of Clostridium beijerinckii. An alcohol dehydrogenase (ADH) has been purified to homogeneity from two strains (NRRL B593 and NESTE 255) of 2-propanol-producing C. beijerinckii. When exposed to air, the purified ADH was stable, whereas the partially purified ADH was inactivated. The ADHs from the two strains had similar structural and kinetic properties. Each had a native M(r) of between 90,000 and 100,000 and a subunit M(r) of between 38,000 and 40,000. The ADHs were NADP(H) dependent, but a low level of NAD(+)-linked activity was detected. They were equally active in reducing aldehydes and 2-ketones, but a much lower oxidizing activity was obtained with primary alcohols than with secondary alcohols. The kcat/Km value for the alcohol-forming reaction appears to be a function of the size of the larger alkyl substituent on the carbonyl group. ADH activities measured in the presence of both acetone and butyraldehyde did not exceed activities measured with either substrate present alone, indicating a common active site for both substrates. There was no similarity in the N-terminal amino acid sequence between that of the ADH and those of fungi and several other bacteria. However, the N-terminal sequence had 67% identity with those of two other anaerobes, Thermoanaerobium brockii and Methanobacterium palustre. Furthermore, conserved glycine and tryptophan residues are present in ADHs of these three anaerobic bacteria and ADHs of mammals and green plants. PMID- 8349552 TI - Roles of the GcvA and PurR proteins in negative regulation of the Escherichia coli glycine cleavage enzyme system. AB - When Escherichia coli was grown in medium containing both inosine and glycine, the PurR repressor protein was shown to be responsible for a twofold reduction from the fully induced glycine cleavage enzyme levels. This twofold repression was also seen by measuring beta-galactosidase levels in cells carrying a lambda gcvT-lacZ gene fusion. In this fusion, the synthesis of beta-galactosidase is under the control of the gcv regulatory region. A DNA fragment carrying the gcv control region was shown by gel mobility shift assay and DNase I footprinting to bind purified PurR protein, suggesting a direct involvement of the repressor in gcv regulation. A separate mechanism of purine-mediated regulation of gcv was shown to be independent of the purR gene product and resulted in an approximately 10-fold reduction of beta-galactosidase levels when cells were grown in medium containing inosine but lacking the inducer glycine. This additional repression was dependent upon a functional gcvA gene, a positive activator for the glycine cleavage enzyme system. A dual role for the GcvA protein as both an activator in the presence of glycine and a repressor in the presence of inosine is suggested. PMID- 8349553 TI - Surface properties of the conidiospores of Phanerochaete chrysosporium and their relevance to pellet formation. AB - The conidiospores of the white rot basidiomycete Phanerochaete chrysosporium tend to aggregate during swelling and germination in agitated liquid medium; as time passes, the initial aggregates tend to associate together and to capture conidiospores that remain isolated. The surface chemical compositions of the conidiospores and of developed hyphae were analyzed by X-ray photoelectron spectroscopy. The data were interpreted by modelling the surface in terms of proteins, polysaccharides and hydrocarbonlike compounds. The surface molecular composition of the dormant conidiospores was estimated to be about 45% proteins, 20% carbohydrates, and 35% hydrocarbonlike compounds. There was an increase in the polysaccharide content during germination. Later, when the hyphae were developed, the polysaccharide content became still higher, and the protein content dropped. The initial step of aggregation is attributed to polysaccharide bridging; its occurrence cannot be explained by a change of the overall hydrophobicity or electrical properties of the conidiospores. PMID- 8349554 TI - Expression analysis of cloned chromosomal segments of Escherichia coli. AB - The novel transcription system of bacteriophage T7 was used to express Escherichia coli genes preferentially with a new low-copy-number plasmid vector, pFN476, to minimize toxic gene effects. Selected E. coli chromosomal fragments from an ordered genomic library (Y. Kohara, K. Ikiyama, and K. Isono, Cell 50:495 508, 1987) were recloned into this vector, and their genes were preferentially expressed in vivo utilizing its T7 promoter. The protein products were analyzed by two-dimensional gel electrophoresis. By using DNA sequence information, the gel migration was predicted for the protein products of open reading frames from these segments, and this information was used to identify gene products visualized as spots on two-dimensional gels. Even in the absence of DNA sequence information, this approach offers the opportunity to identify all gene products of E. coli and map their genes to within 10 kb on the E. coli genome; with sequence information, this approach can produce a definitive expression map of the E. coli genome. PMID- 8349555 TI - Thioredoxin-thioredoxin reductase system of Streptomyces clavuligerus: sequences, expression, and organization of the genes. AB - The genes that encode thioredoxin and thioredoxin reductase of Streptomyces clavuligerus were cloned, and their DNA sequences were determined. Previously, we showed that S. clavuligerus possesses a disulfide reductase with broad substrate specificity that biochemically resembles the thioredoxin oxidoreductase system and may play a role in the biosynthesis of beta-lactam antibiotics. It consists consists of two components, a 70-kDa NADPH-dependent flavoprotein disulfide reductase with two identical subunits and a 12-kDa heat-stable protein general disulfide reductant. In this study, we found, by comparative analysis of their predicted amino acid sequences, that the 35-kDa protein is in fact thioredoxin reductase; it shares 48.7% amino acid sequence identity with Escherichia coli thioredoxin reductase, the 12-kDa protein is thioredoxin, and it shares 28 to 56% amino acid sequence identity with other thioredoxins. The streptomycete thioredoxin reductase has the identical cysteine redox-active region--Cys-Ala-Thr Cys--and essentially the same flavin adenine dinucleotide- and NADPH dinucleotide binding sites as E. coli thioredoxin reductase and is partially able to accept E. coli thioredoxin as a substrate. The streptomycete thioredoxin has the same cysteine redox-active segment--Trp-Cys-Gly-Pro-Cys--that is present in virtually all eucaryotic and procaryotic thioredoxins. However, in vivo it is unable to donate electrons to E. coli methionine sulfoxide reductase and does not serve as a substrate in vitro for E. coli thioredoxin reductase. The S. clavuligerus thioredoxin (trxA) and thioredoxin reductase (trxB) genes are organized in a cluster. They are transcribed in the same direction and separated by 33 nucleotides. In contrast, the trxA and trxB genes of E. coli, the only other organism in which both genes have been characterized, are physically widely separated. PMID- 8349556 TI - Integration and gene replacement in the Lactococcus lactis lac operon: induction of a cryptic phospho-beta-glucosidase in LacG-deficient strains. AB - Insertions, replacement mutations, and deletions were introduced via single or double crossover recombination into the lacE (enzyme IIlac) and lacG (phospho beta-galactosidase) genes of the Lactococcus lactis chromosomal lacABCDFEGX operon. LacG production was abolished in strains missing the lacG gene or carrying multicopy insertions in the lacE gene that affected expression of the lacG gene. However, these LacG-deficient strains could still ferment lactose slowly and were found to contain an enzymatic activity that hydrolyzed the chromogenic substrate o-nitrophenyl-beta-D-galactopyranoside phosphate. Induction of this phospho-beta-glycohydrolase activity coincided with the appearance of a new 55-kDa protein cross-reacting with anti-LacG antibodies that had a size similar to that of LacG but a higher isoelectric point (pI 5.2) and was not found in wild-type cells during growth on lactose. Since the phospho-beta glycohydrolase activity and this protein with a pI of 5.2 were highly induced in both mutant and wild-type cells during growth on cellobiose that is likely to be transported via a phosphoenolpyruvate-dependent phosphotransferase system, we propose that this induced activity is a phospho-beta-glucosidase that also hydrolyzes lactose-6-phosphate. PMID- 8349557 TI - Genetic analysis of double-strand break repair in Escherichia coli. AB - We had reported that a double-strand gap (ca. 300 bp long) in a duplex DNA is repaired through gene conversion copying a homologous duplex in a recB21 recC22 sbcA23 strain of Escherichia coli, as predicted on the basis of the double-strand break repair models. We have now examined various mutants for this repair capacity. (i) The recE159 mutation abolishes the reaction in the recB21C22 sbcA23 background. This result is consistent with the hypothesis that exonuclease VIII exposes a 3'-ended single strand from a double-strand break. (ii) Two recA alleles, including a complete deletion, fail to block the repair in this recBC sbcA background. (iii) Mutations in two more SOS-inducible genes, recN and recQ, do not decrease the repair. In addition, a lexA (Ind-) mutation, which blocks SOS induction, does not block the reaction. (iv) The recJ, recF, recO, and recR gene functions are nonessential in this background. (v) The RecBCD enzyme does not abolish the gap repair. We then examined genetic backgrounds other than recBC sbcA, in which the RecE pathway is not active. We failed to detect the double strand gap repair in a rec+, a recA1, or a recB21 C22 strain, nor did we find the gap repair activity in a recD mutant or in a recB21 C22 sbcB15 sbcC201 mutant. We also failed to detect conservative repair of a simple double-strand break, which was made by restriction cleavage of an inserted linker oligonucleotide, in these backgrounds. We conclude that the RecBCD, RecBCD-, and RecF pathways cannot promote conservative double-strand break repair as the RecE and lambda Red pathways can. PMID- 8349558 TI - Cloning and assessment of mycobacterial promoters by using a plasmid shuttle vector. AB - We have constructed a promoter selection vector for mycobacteria to analyze the sequences involved in mycobacterial transcriptional regulation. The vector pSD7 contains extrachromosomal origins of replication from Escherichia coli as well as from Mycobacterium fortuitum and a kanamycin resistance gene for positive selection in mycobacteria. The promoterless chloramphenicol acetyltransferase (CAT) reporter gene has been used to detect mycobacterial promoter elements in a homologous environment and to quantify their relative strengths. Using pSD7, we have isolated 125 promoter clones from the slowly growing pathogen Mycobacterium tuberculosis H37Rv and 350 clones from the fast-growing saprophyte Mycobacterium smegmatis. The promoters exhibited a wide range of strengths, as indicated by their corresponding CAT reporter activities (5 to 2,500 nmol/min/mg of protein). However, while most of the M. smegmatis promoters supported relatively higher CAT activities ranging from 100 to 2,500 nmol/min/mg of protein, a majority of those from M. tuberculosis supported CAT activities ranging from 5 to only about 100 nmol/min/mg of protein. Our results indicate that stronger promoters occur less frequently in the case of M. tuberculosis compared with M. smegmatis. To assess the extent of divergence of mycobacterial promoters vis-a-vis those of E. coli, the CAT activities supported by the promoters in E. coli were measured and compared with their corresponding activities in mycobacteria. Most of the mycobacterial promoter elements functioned poorly in E. coli. The homologous selection system that we have developed has thus enabled the identification of mycobacterial promoters that apparently function optimally only in a native environment. PMID- 8349559 TI - The Rhizobium meliloti rhizopine mos locus is a mosaic structure facilitating its symbiotic regulation. AB - The Rhizobium meliloti L5-30 mos locus, encoding biosynthesis of the rhizopine 3 O-methyl-scyllo-inosamine, is shown to be a mosaic structure. The mos locus consists of four open reading frames (ORFs) (ORF1 and mosABC) arranged in an operon structure. Within this locus, several domains of homology with other prokaryotic symbiotic genes (nifH, fixA, fixU, and nifT) are present, suggesting that this locus may represent a hot spot for rearrangement of symbiotic genes. Unusually, these domains are present in the coding as well as noncoding regions of the mos locus. Proteins corresponding to those encoded by mosABC, but not ORF1, have been detected in nodule extracts by using antibodies. As ORF1 shows extensive homology with the 5' region of the nifH gene (P.J. Murphy, N. Heycke, S.P. Trenz, P. Ratet, F.J. de Bruijn, and J. Schell, Proc. Natl. Acad. Sci. USA 85:9133-9137, 1988) and a frameshift mutation indicates that expression of this ORF is not required for mos activity, we propose that the mos locus has acquired a duplicated copy of nifH, including the promoter region, in order to become symbiotically regulated. Surprisingly, since the functions are likely different, MosA has an amino acid sequence similar to that of the DapA protein of Escherichia coli. The central domain of MosB has extensive homology with a range of diverse proteins involved with carbohydrate metabolism in either antibiotic or outer-cell-wall biosynthesis. This region is also common to the regulatory proteins DegT and DnrJ, suggesting a regulatory role for MosB. The structure of MosC is consistent with its being a membrane transport protein. PMID- 8349561 TI - Generation of restriction map of Enterococcus faecalis OG1 and investigation of growth requirements and regions encoding biosynthetic function. AB - A defined synthetic medium was used to determine the amino acid requirements of Enterococcus faecalis OG1 and to demonstrate the absence of a requirement for exogenous purines or pyrimidines. Genomic libraries prepared from strain OG1 were transduced into Escherichia coli auxotrophic mutants, and cloned DNAs which complemented pyrC, pyrD, purF, purL, and guaAB mutations were identified. These and other cloned DNAs with known functions were localized on a restriction map of OG1 which was generated with SfiI (5 fragments), AscI (9 fragments), and NotI (15 fragments); the size of the OG1 chromosome was revised from a previous estimate of approximately 2,750 kb to 2,825 kb. The synthetic medium and the restriction map should be useful for studying enterococcal metabolic functions and the relationships between chromosomally encoded genes. PMID- 8349560 TI - Characterization of genes for synthesis and catabolism of a new rhizopine induced in nodules by Rhizobium meliloti Rm220-3: extension of the rhizopine concept. AB - Rhizopines are selective growth substrates synthesized in nodules only by strains of rhizobia capable of their catabolism. We report the isolation and study of genes for the synthesis and catabolism of a new rhizopine, scyllo-inosamine (sIa), from alfalfa nodules induced by Rhizobium meliloti Rm220-3. This compound is similar in structure to the previously described rhizopine 3-O-methyl-scyllo inosamine from R. meliloti L5-30 (P.J. Murphy, N. Heycke, Z. Banfalvi, M.E. Tate, F.J. de Bruijn, A. Kondorosi, J. Tempe, and J. Schell, Proc. Natl. Acad. Sci. USA 84:493-497, 1987). The synthesis (mos) and catabolism (moc) genes for the Rm220-3 rhizopine are closely linked and located on the nod-nif Sym plasmid. The mos genes are directly controlled by the NifA/NtrA regulatory system. A comparison of the sequence of the 5' regions of the two mos loci shows very extensive conservation of sequence as well as strong homology to the nifH coding region. Restriction mapping and hybridization to DNA from the four open reading frames (ORFs) of the L5-30 mos locus indicate the absence of mosA and presence of the other three ORFs (ORF1 and mosB and -C) in Rm220-3. We suggest that the L5-30 mosA gene product is involved in the conversion of scyllo-inosamine to 3-O-methyl scyllo-inosamine. Restriction fragment length polymorphism analysis of the moc regions of both strains shows that they are very similar. Regulation studies indicate that the moc region is not controlled by the common regulatory gene nifA, ntrA, and ntrC. We discuss the striking similarities in gene structure, location, and regulation between these two rhizopine loci in relation to the rhizopine concept. PMID- 8349562 TI - Gene components responsible for discrete substrate specificity in the metabolism of biphenyl (bph operon) and toluene (tod operon). AB - bph operons coding for biphenyl-polychlorinated biphenyl degradation in Pseudomonas pseudoalcaligenes KF707 and Pseudomonas putida KF715 and tod operons coding for toluene-benzene metabolism in P. putida F1 are very similar in gene organization as well as size and homology of the corresponding enzymes (G. J. Zylstra and D. T. Gibson, J. Biol. Chem. 264:14940-14946, 1989; K. Taira, J. Hirose, S. Hayashida, and K. Furukawa, J. Biol. Chem. 267:4844-4853, 1992), despite their discrete substrate ranges for metabolism. The gene components responsible for substrate specificity between the bph and tod operons were investigated. The large subunit of the terminal dioxygenase (encoded by bphA1 and todC1) and the ring meta-cleavage compound hydrolase (bphD and todF) were critical for their discrete metabolic specificities, as shown by the following results. (i) Introduction of todC1C2 (coding for the large and small subunits of the terminal dioxygenase in toluene metabolism) or even only todC1 into biphenyl utilizing P. pseudoalcaligenes KF707 and P. putida KF715 allowed them to grow on toluene-benzene by coupling with the lower benzoate meta-cleavage pathway. Introduction of the bphD gene (coding for 2-hydroxy-6-oxo-6-phenylhexa-2,4 dienoate hydrolase) into toluene-utilizing P. putida F1 permitted growth on biphenyl. (ii) With various bph and tod mutant strains, it was shown that enzyme components of ferredoxin (encoded by bphA3 and todB), ferredoxin reductase (bphA4 and todA), and dihydrodiol dehydrogenase (bphB and todD) were complementary with one another. (iii) Escherichia coli cells carrying a hybrid gene cluster of todClbphA2A3A4BC (constructed by replacing bphA1 with todC1) converted toluene to a ring meta-cleavage 2-hydroxy-6-oxo-hepta-2,4-dienoic acid, indicating that TodC1 formed a functional multicomponent dioxygenase associated with BphA2 (a small subunit of the terminal dioxygenase in biphenyl metabolism), BphA3, and BphA4. PMID- 8349563 TI - Subcellular localization of seven VirB proteins of Agrobacterium tumefaciens: implications for the formation of a T-DNA transport structure. AB - Plant cell transformation by Agrobacterium tumefaciens involves the transfer of a single-stranded DNA-protein complex (T-complex) from the bacterium to the plant cell. One of the least understood and important aspects of this process is how the T-complex exits the bacterium. The eleven virB gene products have been proposed to specify the DNA export channel on the basis of their predicted hydrophobicity. To determine the cellular localization of the VirB proteins, two different cell fractionation methods were employed to separate inner and outer membranes. Seven VirB-specific antibodies were used on Western blots (immunoblots) to detect the proteins in the inner and outer membranes and soluble (containing cytoplasm and periplasm) fractions. VirB5 was in both the inner membrane and cytoplasm. Six of the VirB proteins were detected in the membrane fractions only. Three of these, VirB8, VirB9, and VirB10, were present in both inner and outer membrane fractions regardless of the fractionation method used. Three additional VirB proteins, VirB1, VirB4, and VirB11, were found mainly in the inner membrane fraction by one method and were found in both inner and outer membrane fractions by a second method. These results confirm the membrane localization of seven VirB proteins and strengthen the hypothesis that VirB proteins are involved in the formation of a T-DNA export channel or gate. That most of the VirB proteins analyzed are found in both inner and outer membrane fractions suggest that they form a complex pore structure that spans both membranes, and their relative amounts in the two membrane fractions reflect their differential sensitivity to the experimental conditions. PMID- 8349564 TI - Characterization of twenty-six new heat shock genes of Escherichia coli. AB - Most organisms respond to heat by substantial alteration of the pattern of gene expression. This has been particularly well studied with Escherichia coli although the response has by no means been completely characterized. Here we report the characterization of 26 new heat shock genes of E. coli, termed hsl, discovered by global transcription analysis with an overlapping lambda clone bank. We have measured the molecular weights of the corresponding heat shock proteins and mapped each of them to within a few kilobases on the E. coli genome. In vitro, 16 of them can be activated by the E sigma 32 RNA polymerase, which specifically transcribes heat shock genes. In vivo expression kinetics of seven of eight examined new proteins were found to be similar to those of the four most studied heat shock proteins, DnaK, DnaJ, GroEL (MopA), and GroES (MopB). In the course of this work, we confirmed that the catalytic subunit of the ATP-dependent Clp protease (also known as Ti protease), ClpP, is derived from a larger precursor protein. Possible assignments of some of the hsl genes to known proteins are discussed. PMID- 8349565 TI - Cloning and characterization of a region of the Enterococcus faecalis conjugative plasmid, pCF10, encoding a sex pheromone-binding function. AB - In order to investigate the mechanism by which peptide sex pheromones induce expression of the conjugation functions of certain Enterococcus faecalis plasmids, a biological assay was developed to measure the ability of cells carrying the conjugative plasmid pCF10 to bind the sex pheromone cCF10. The data indicated that pCF10 endows its host E. faecalis cell with the ability to specifically remove (apparently by irreversible binding) cCF10 activity from culture medium. The pCF10 DNA encoding this ability was localized to a 3.4-kb segment within a region involved in negative control of expression of conjugal transfer functions. This segment also encoded ability to bind the pheromone inhibitor peptide iCF10. DNA sequencing revealed three open reading frames, which have been denoted prgW (pheromone responsive gene W), prgZ, and prgY. The deduced product of prgW resembled regulatory proteins from other bacteria and eucaryotes, with a very high degree of identity within a putative DNA-binding domain. The prgY gene actually extended into an adjacent region of pCF10 and could encode a protein with significant similarity to a protein called TraB, believed to be involved in shutdown of pheromone cAD1 production by cells carrying the pheromone inducible hemolysin plasmid pAD1, according to F.Y. An and D.B. Clewell (Abstr. Gen. Meet. Am. Soc. Microbiol. 1992, H70, 1992). The prgZ gene product showed significant relatedness to binding proteins encoded by oligopeptide permease (opp) operons in gram-positive and gram-negative bacteria and is highly similar to a pAD1-encoded protein, TraC, which is believed to mediate sex pheromone cAD1 binding (K. Tanimoto, F. Y. An, and D. B. Clewell, submitted for publication). A Tn5 insertion into prgZ abolished cCF10 binding ability. PMID- 8349567 TI - The outer membranes of Brucella spp. are not barriers to hydrophobic permeants. AB - The patterns of susceptibility to hydrophobic and hydrophilic drugs and the uptake of the fluorescent probe N-phenyl-naphthylamine in Brucella spp., Haemophilus influenzae, Escherichia coli, and deep rough Salmonella minnesota mutants were compared. The results show that the outer membranes of smooth and naturally rough Brucella spp. do not represent barriers to hydrophobic permeants and that this absence of a barrier relates at least in part to the properties of Brucella lipopolysaccharide. PMID- 8349566 TI - Characterization of the traC determinant of the Enterococcus faecalis hemolysin bacteriocin plasmid pAD1: binding of sex pheromone. AB - pAD1, a conjugative, 60-kb, hemolysin-bacteriocin plasmid in Enterococcus faecalis, encodes a mating response to a small peptide sex pheromone, cAD1, secreted by potential recipient bacteria. A gene, traC, encoding a 60.7-kDa protein with a typical amino terminal signal peptide, was identified within a region that appears to encode a product that binds to exogenous pheromone. A cloned segment of DNA containing traC resulted in specific binding of cells to synthetic cAD1. The putative traC product has strong similarity to a product of the E. faecalis plasmid pCF10 as well as oligopeptide binding proteins of Escherichia coli, Salmonella typhimurium, and Bacillus subtilis. PMID- 8349568 TI - A 20-kilodalton protein preserves cell viability and promotes CytA crystal formation during sporulation in Bacillus thuringiensis. AB - The effect of a 20-kDa protein on cell viability and CytA crystal production in its natural host, Bacillus thuringiensis, was studied by expressing the cytA gene in the absence or presence of this protein. In the absence of the 20-kDa protein, B. thuringiensis cells either were killed during sporulation (strain cryB) or produced very small CytA crystals (strain 4Q7). Expression of cytA in the presence of the 20-kDa protein, however, preserved cell viability, especially in strain cryB, and in both strains yielded bipyramidal crystals of the CytA protein that were larger than those of wild-type B. thuringiensis. These results suggest that the 20-kDa protein promotes crystal formation, perhaps by chaperoning CytA molecules during synthesis and crystallization, concomitantly preventing the CytA protein from interacting lethally with the bacterial host cell. PMID- 8349569 TI - Identification of Mycoplasma pirum genes involved in the salvage pathways for nucleosides. AB - Genes encoding enzymes involved in the salvage pathway for nucleosides have been cloned and sequenced from the mollicute Mycoplasma pirum. One of them, encoding deoxyriboaldolase, was functionally identified by complementation of an Escherichia coli mutant. These genes are clustered, suggesting an operon organization, and they are immediately followed by the putative gene for the triose phosphate isomerase, an enzyme used during glycolysis. PMID- 8349570 TI - Genes for the establishment and maintenance of lysogeny by the temperate coliphage 186. AB - To identify the genes in coliphage 186 that are required for lysogeny, we isolated clear-plaque mutants. Complementation studies and DNA sequencing identified two genes, the cI gene for the immunity maintenance repressor and the cII gene, which is required only for the establishment of lysogeny. One mutant carried a change in the LexA-binding site controlling expression of the antirepression protein Tum. PMID- 8349571 TI - Immunocytochemical analysis of poly-beta-hydroxybutyrate (PHB) synthase in Alcaligenes eutrophus H16: localization of the synthase enzyme at the surface of PHB granules. AB - Antibodies raised against the Alcaligenes eutrophus poly-beta-hydroxybutyrate (PHB) synthase polypeptide were used for immunocytochemical localization of the synthase enzyme in whole cells and purified PHB granules. The data presented demonstrate for the first time that the synthase enzyme is located on the surface of the PHB granule rather than being incorporated inside the granule during its formation. From these basic observations and data from the recent literature, a model of granule assembly is proposed. PMID- 8349572 TI - Vi I typing phage for generalized transduction of Salmonella typhi. AB - Salmonella typhi Vi typing phages were used to transduce temperature-sensitive (Ts) mutants of Salmonella typhi. Antibiotic resistance and Ts+ markers were transduced at high frequency (> 10(-4) per virulent phage). Several markers were cotransduced by phage Vi I, suggesting that it may be useful for mapping studies of the S. typhi genome. PMID- 8349573 TI - Complementation of a Chlamydomonas reinhardtii mutant defective in the nuclear gene encoding the chloroplast coupling factor 1 (CF1) gamma-subunit (atpC). AB - Chlamydomonas reinhardtii strain atpC1 is a mutant defective in the nuclear gene that encodes the CF1 ATP synthase gamma-subunit polypeptide. Photoautotrophic growth was restored to atpC1 after it was transformed with wild-type DNA. Transformed strains were acetate-independent and arsenate-sensitive, similar in phenotype to the progenitor wild-type strain from which atpC1 was generated. Three transformed strains were examined in detail. Southern blot analyses demonstrated that the transformants were complements and not revertants. The transforming DNA integrated into the nuclear genome in a nonhomologous manner and at a low copy number. Northern blot analyses showed that the gamma-subunit mRNA in the complemented strains was expressed at the same relative level as that of wild-type. Western blots of total protein showed that whereas atpC1 was unable to synthesize any CF1 gamma-subunit, all three complemented strains could. Furthermore, the Western blot analyses demonstrated that the mutation in atpC1 had a pleiotropic effect on the accumulation of the CF1 beta-subunit which was relieved upon complementation. Cell extracts from atpC1 did not have any CF1 dependent catalytic activity, whereas extracts from all of the complemented strains and the wild-type strain had identical activities. PMID- 8349574 TI - Effects of Zn2+ on the activity and binding of the mitochondrial ATPase inhibitor protein, IF1. AB - Zn2+ caused a noninhibitory binding of IF1 to mitochondrial membranes in both rabbit heart SMP and intact rabbit heart mitochondria. This Zn(2+)-induced IF1 binding required the presence of at least trace amounts of MgATP and was essentially independent of pH between 6.2 and 8.2. Addition of Zn2+ after the formation of fully inhibited IF1-ATPase complexes very slowly reversed IF1 mediated ATPase inhibition without causing significant IF1 release from the membranes. When Zn2+ was added during the state 4 energization of ischemic mitochondria in which IF1 was already functionally bound, it slowed somewhat energy-driven ATPase activation. This slowing was probably due to the fairly large depressing effect Zn2+ had upon membrane potential development, but Zn2+ did not decrease the degree of ATPase activation eventually reached at 20 min of state 4 incubation. Zn2+ also preempted normal IF1 release from the membranes, causing what little inhibitor that was released to rebind to the enzyme in noninhibitory IF1-ATPase complexes. The data suggest that IF1 can interact with the ATPase in two ways of through two kinds of sites: (a) a noninhibitory interaction involving a non-inhibitory IF1 conformation and/or an IF1 docking site on the enzyme and (b) an inhibitory interaction involving an inhibitory IF1 conformation and/or a distinct ATPase activity regulatory site. Zn2+ appears to have the dual effect of stabilizing the noninhibitory IF1-ATPase interaction and possibly a noninhibitory IF1 conformation while concomitantly preventing the formation of an inhibitory IF1-ATPase interaction and possibly an inhibitory IF1 conformation, regardless of pH. While the data do not rule out direct effects of Zn2+ on either free IF1 or the free enzyme, they suggest that Zn2+ cannot interact readily with either the inhibitor or the enzyme once functional IF1 ATPase complexes are formed. PMID- 8349576 TI - Nucleotide excision repair, a tracking mechanism in search of damage. PMID- 8349575 TI - Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone. AB - Dehydroepiandrosterone (DHEA) treatment of rats decreases gain of body weight without affecting food intake; simultaneously, the activities of liver malic enzyme and cytosolic glycerol-3-P dehydrogenase are increased. In the present study experiments were conducted to test the possibility that DHEA enhances thermogenesis and decreases metabolic efficiency via transhydrogenation of cytosolic NADPH into mitochondrial FADH2 with a consequent loss of energy as heat. The following results provide evidence which supports the proposed hypothesis: (a) the activities of cytosolic enzymes involved in NADPH production (malic enzyme, cytosolic isocitrate dehydrogenase, and aconitase) are increased after DHEA treatment; (b) cytosolic glycerol-3-P dehydrogenase may use both NAD+ and NADP+ as coenzymes; (c) activities of both cytosolic and mitochondrial forms of glycerol-3-P dehydrogenase are increased by DHEA treatment; (d) cytosol obtained from DHEA-treated rats synthesizes more glycerol-3-P during incubation with fructose-1,6-P2 (used as source of dihydroxyacetone phosphate) and NADP+; the addition of citrate in vitro further increases this difference; (e) mitochondria prepared from DHEA-treated rats more rapidly consume glycerol-3-P added exogenously or formed endogenously in the cytosol in the presence of fructose-1,6-P2 and NADP+. PMID- 8349577 TI - Binding of wild type and chimeric arrestins to the m2 muscarinic cholinergic receptor. AB - Arrestins play an important role in regulating the activity of the G protein coupled receptors rhodopsin and the beta 2-adrenergic receptor. Recently, we described the expression and functional characterization of visual arrestin using an in vitro translation system. Here we report the expression of beta-arrestin and development of a direct binding assay to study the interaction of arrestins with a muscarinic cholinergic receptor. In vitro translated beta-arrestin was found to specifically bind to purified reconstituted human m2 muscarinic cholinergic receptor (hm2 mAChR) in an agonist- and phosphorylation-dependent manner. Visual arrestin also bound to the hm2 mAChR, albeit to a lesser extent and with lower affinity. In an attempt to dissect the major domains responsible for determining the receptor binding specificity of arrestin and beta-arrestin, we generated several chimeric arrestins. One contained the first 340 residues of beta-arrestin followed by residues 346-404 of arrestin (BRV4), another consisted of the first 207 residues of beta-arrestin and residues 214-404 of visual arrestin (BV3), and a third had residues 1-43 of beta-arrestin replaced by residues 1-47 of arrestin (VIN1). All of these arrestins were able to specifically bind to the activated and phosphorylated form of both the hm2 mAChR and rhodopsin, with a clear preference for the muscarinic receptor. The Kd values for beta-arrestin, BRV4, BV3, VIN1, and visual arrestin binding to the hm2 mAChR were 0.48 +/- 0.06, 0.51 +/- 0.19, 1.38 +/- 0.26, 1.13 +/- 0.26, and 7.2 +/- 1.2 nM, respectively. These data demonstrate that: 1) beta-arrestin binds to the hm2 mAChR in an activation- and phosphorylation-dependent fashion, 2) visual arrestin has 15-fold lower affinity for the hm2 mAChR as compared to beta-arrestin, and 3) the N-terminal half of beta-arrestin plays a key role in determining receptor binding specificity. The use of in vitro translated arrestins to directly assess receptor binding may serve as a viable approach for elucidating the specificity and molecular mechanisms involved in receptor-arrestin interaction. PMID- 8349578 TI - Myosin light chain phosphorylation does not increase during yeast phagocytosis by macrophages. AB - We have studied the role of myosin II light chain phosphorylation in yeast phagocytosis by J774 cells. J774 cells, which are mouse cells of monocyte/macrophage lineage, ingest opsonized yeast particles, and the rate of internalization is linear for 60 min at 37 degrees C. Immunoprecipitation of myosin II from cells labeled with 32P, using an affinity-purified antibody to myosin II purified from J774 cells, demonstrated phosphorylation of both the myosin heavy chain and the 20-kDa light chain (PMLC) prior to the addition of the opsonized yeast. However, the levels of heavy chain and PMLC phosphorylation did not change during the linear phase of yeast uptake by J774 cells. Other experiments demonstrated that the amount of myosin II associated with the cytoskeleton did not change during phagocytosis, further supporting the observation that PMLC phosphorylation does not increase during phagocytosis. In contrast, F-actin increased by 1.6-fold during the linear phase of phagocytosis. Two additional approaches were used to analyze in greater detail the role of myosin II phosphorylation in phagocytosis. First, antibodies to myosin light chain kinase (MLCK), the enzyme that phosphorylates PMLC, were electroinjected into J774 cells. These antibodies, which inhibit MLCK activity, inhibited chemotaxis as previously described but had no effect on phagocytosis. Second, quantitation of phagocytosis and chemotaxis following treatment with the phosphoprotein phosphatase inhibitor okadaic acid demonstrated that chemotaxis was much more sensitive than phagocytosis to okadaic acid treatment; at 0.3 microM okadaic acid, there is a substantial increase in myosin phosphorylation and chemotaxis is inhibited by 60%, whereas phagocytosis is unaffected. These data indicate that PMLC phosphorylation and, by implication, myosin II are not involved in yeast phagocytosis. They also suggest that PMLC phosphorylation displays a high degree of specificity with respect to mediating energy-dependent cellular processes in macrophages. PMID- 8349579 TI - The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells. AB - Mast cells release the mediators of the immediate hypersensitivity reaction. Adenosine is known to modulate this process, but the receptor responsible for this is not the classical A1 or A2 adenosine receptors. This study was undertaken to determine whether the unique adenosine receptor (AR) previously postulated in a cultured mast cell line (RBL-2H3 cells) is the recently cloned A3AR. The receptors were quantitated by the agonist 125I-labeled APNEA (aminophenylethyladenosine), an A3AR agonist, which yielded Bmax and Kd values of 826 fmol/mg protein and 34 nM, respectively. A variety of adenosine analogs competed for 125I-APNEA binding sites with the following potency series: (R) phenylisopropyladenosine = 5'-N-ethylcarboxamide adenosine > (S) phenylisopropyladenosine. 125I-APNEA binding was relatively insensitive to the xanthine amine congener (XAC, 1 microM), a selective antagonist for the A1AR. Functionally, activation of these A3AR stimulated the production of inositol 1,4,5-triphosphate, leading to an increase in the level of intracellular Ca2+. Furthermore, while activation of these receptors alone produced little secretory response in RBL-2H3 cells, it enhanced antigen-induced secretion by 2-2.5-fold. Northern blotting studies using poly(A+) RNA from RBL-2H3 cells detected two transcripts of 2.0 and 3.5 kilobases, which hybridized to an A3AR cDNA but not to the A1 or A2AR cDNA probes. These data indicate that the unique AR that potentiates the secretory response to antigen in RBL-2H3 cells is exclusively the A3AR. PMID- 8349580 TI - Inhibition of the cellular secretion of cholesteryl ester transfer protein by a variant protein formed by alternative splicing of mRNA. AB - Alternative splicing of mRNA is often used as a regulatory switch, determining whether a functional protein is made or not. The plasma cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high density lipoproteins to other lipoproteins. In addition to the mRNA encoding plasma CETP, human tissues contain an alternatively spliced variant in which exon 9-derived sequences are omitted. To determine a possible regulatory role of alternative splicing, COS cells were co-transfected with full-length and exon 9 deleted cDNAs. The exon 9-deleted protein was poorly secreted and inhibited the secretion of full-length CETP, due to formation of an intracellular heteromeric complex between full-length and exon 9-deleted proteins. The findings suggest a novel use of alternative splicing to generate a poorly secreted protein variant, which complexes with the active form and prevents its secretion by cells. PMID- 8349581 TI - Thrombin exosite for fibrinogen recognition is partially accessible in prothrombin. AB - The procoagulant alpha-thrombin is produced by the proteolytic cleavages of a minimum of two peptide bonds Arg274-Thr275 and Arg323-Ile324 in prothrombin. The Arg323-Ile324 cleavage is required for the expression of the active site of thrombin (Morita, T., Iwanaga, S. Suzuki, T. (1976) J. Biochem. (Tokyo) 79, 1089 1108; Hibbard, L. S., Nesheim, M. E., and Mann, K. G. (1982) Biochemistry 21, 2285-2292). It is not yet clear to what extent the proteolytic events are responsible for exposing protein recognition exosites on thrombin. We employed high resolution NMR spectroscopy to examine interactions of prothrombin and thrombin with synthetic hirudin peptides targeted toward the fibrinogen recognition exosite of thrombin. The hirudin tail synthetic analogues (acetyl Asp55-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-Gln65/G ly65-OH) exhibited similar NMR relaxation enhancements (line broadening patterns and transferred nuclear Overhauser effects) with human prothrombin as with human alpha-thrombin, indicating that both proteins bind the peptide in a similar manner. The protein induced relaxation enhancements are specific to the interaction of the hirudin peptides with the fibrinogen recognition exosite of thrombin since no significant effects were observed with either human serum albumin or with human gamma thrombin, which has an impaired recognition exosite. The binding affinities were determined from NMR relaxation time measurements, which gave approximate Kd values of 500 microM and < 100 microM for prothrombin and alpha-thrombin, respectively. Since the hirudin tail fragment binds specifically to the fibrinogen recognition exosite in alpha-thrombin, this exosite appears to be partially accessible in prothrombin in a proenzyme form. PMID- 8349582 TI - Human ABR encodes a protein with GAPrac activity and homology to the DBL nucleotide exchange factor domain. AB - We have previously cloned a segment of a gene, ABR, homologous to the BCR gene, which encodes a protein consisting of three distinct functional domains. In the present study, genomic ABR sequences were used to isolate human ABR cDNAs. Surprisingly, the two types of ABR cDNAs identified differed only in their most 5' coding sequences. These are predicted to encode proteins of 93.5 and 92.3 kDa molecular mass. ABR showed a differential expression pattern in various mouse tissues, analogous to that of BCR, and the highest level was found in brain. Similar to BCR, ABR contains a region with homology to DBL, vav, and CDC24, which are likely to or have been shown to encode GTP exchange factors. A domain of ABR with similarity to GAPrho was expressed as a fusion protein in Escherichia coli and was shown to have GAP activity toward rac. Although both ABR and BCR have GAP activity, ABR lacks homology to the serine/threonine kinase domain of BCR. Therefore, ABR is likely to have cellular functions overlapping with but also distinct from those of BCR. PMID- 8349583 TI - The tricarboxylic acid cycle in Dictyostelium discoideum. Systemic effects of including protein turnover in the current model. AB - The current model for the tricarboxylic acid cycle in Dictyostelium discoideum is based on extensive experimental studies of enzyme kinetics in vitro and of metabolite fluxes measured in vivo. In the previous papers (Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22912-22918; 22919-22925; 22926-22933; 22934-22943) of this series we have carried out extensive analyses of the current model within the framework of biochemical systems theory with a view toward understanding the behavior of the integrated system. The model was found to be ill determined with respect to at least three of its features. In this paper we propose a minimal modification in the model that is consistent with previous experimental data but also includes recycling of amino acids for protein synthesis, one of the neglected features identified as important in the previous analysis. We again perform an analysis within the framework of biochemical systems theory to determine the systemic consequences of this change. The results show that the robustness of the modified model, as determined by the parameter sensitivities, is improved by 2 orders of magnitude over that of the previous model. Analysis of the dynamics shows that the turnover times for the pools of alanine, glutamate, and aspartate are reduced by 2 orders of magnitude and made more physiologically realistic. The distribution of flux is no longer rigidly fixed, and problems previously centered on the metabolism of pyruvate have been partially alleviated. Continued discrepancies lead us to question the degree to which kinetic data obtained with purified enzymes in vitro faithfully reflect the kinetic behavior of the integrated enzyme system in vivo. We must continue to re examine the manner in which the kinetics of reactions in vivo are represented and to reassess the physical conditions that prevail in vitro and in vivo. Results in this paper direct our attention toward specific aspects of the system where these efforts should be focused. Thus, a minimal modification of the previous model has led to several improvements that make it more representative of the tricarboxylic acid cycle in D. discoideum, and the analysis in this paper leads to further predictions for improving the model. PMID- 8349584 TI - A vectorized sequence-coupling model for predicting HIV protease cleavage sites in proteins. AB - What kind of peptide sequences can be cleaved by HIV protease, and what kind cannot be? This is a crucially important problem in designing effective inhibitors against HIV protease as potential drugs for AIDS therapy. To tackle this problem, a sequence-coupling and vectorized model is proposed for predicting the cleavability of oligopeptides by proteases with multiple and extended specificity subsites. In comparison with existing methods, the new method has proved to be an improvement in both the accuracy of the model and the rationality of the statistical treatment. Meanwhile, the Monte Carlo sampling procedure introduced here has also proved to be very useful in dealing with the situation when the experimental data are insufficiently sampled for complete statistics. Owing to its very high rate of correct prediction, it is expected that the new method can be a useful technique for helping to find effective inhibitors of HIV protease, which is one of the targets in designing potential drugs against AIDS. The principle of the new method can also be applied to analyzing the specificity of any multi-subsite enzyme. PMID- 8349586 TI - Isolation and analysis of the gene and cDNA for a human Mu class glutathione S transferase, GSTM4. AB - We have isolated the human gene and cDNA that encode the fourth member of the Mu class glutathione S-transferases (GSTs). The complete gene sequence (GenBank M96233) and the cDNA sequence (M96234) are reported and named GSTM4. The gene, located on chromosome 1, is comprised of eight exons with an organization similar to that of other Mu class genes. GSTM4 differs from a partial gene sequence, termed GSTmu2 (Taylor, J. B., Oliver, J., Sherrington, R., and Pemble, S. E. (1991) Biochem. J. 274, 587-593), in exons 3 through 5 by only 11 nucleotides within introns. The cDNA for GSTM4 was isolated from a library derived from the cervical carcinoma cell line, HeLa. Northern blots demonstrate the presence of GSTM4 mRNA in human heart, placenta, lung, brain, liver, skeletal muscle, pancreas, testis, cerebral cortex, uterus, ovary, a lymphoblastoid cell line, and four carcinoma cell lines. The deduced amino acid sequence of GSTM4 is 87% (GSTM1), 83% (GSTM2), and 70% (GSTM3) identical to the previously described human Mu class GSTs. The polypeptide encoded by the GSTM4 cDNA, produced in a bacterial expression system, conjugates 1-chloro-2,4-dinitrobenzene to GSH with a specific activity of 1.39 +/- 0.21 mumol/min/mg. PMID- 8349585 TI - Detection and characterization of cellular EGR-1 binding to its recognition site. AB - Most of what is known of the Egr-1 DNA binding site GCGGGGGCG was originally identified by experiments using DNA sequences and bacterially expressed or in vitro translated EGR-1 protein. Here we report the binding of cellular EGR-1 protein derived from HeLa, mouse and human fibroblasts to its consensus sequence. Binding is strongly but transiently stimulated in these cells by serum, phorbol ester, or by okadaic acid, an inhibitor of protein serine/threonine phosphatases 1 and 2A, suggesting the regulation of this gene expression and its DNA binding activity to be under the control of protein kinase(s) and phosphatase(s). When EGR-1 synthesis is stimulated under the above conditions, binding of the transcription factor Sp1 to its recognition site in the Egr-1 promoter is reduced with a concomitant appearance of EGR-1 DNA binding. This is likely a result of competition between Sp1 and the newly synthesized EGR-1, since there is a partial overlap in the binding sequences recognized by these proteins. In cotransfection experiments EGR-1 activated transcription through multiple copies of GCGGGGGCG 5' to a minimum promoter of c-fos. Interestingly, EGR-1 is shown to down-regulate the transcription of its own gene expression, whereas Sp1 activated Egr-1 gene expression. The detection of cellular EGR-1 binding to the Egr-1 consensus sequence in the different cell types provides a model for studying the mechanism by which an immediate-early gene is regulated by various ligands. PMID- 8349587 TI - Microheterogeneity around the reactive lysine residue in the myosin heavy chain from rabbit skeletal muscle. AB - A molecule of myosin subfragment 1 (S1) from rabbit skeletal muscle has one highly reactive lysine residue, Lys-83 (RLR), in the heavy chain, which is rapidly and stoichiometrically modified by trinitrobenzenesulfonate. Our previous kinetic study (Komatsu, H., Emoto, Y., and Tawada K. (1993) J. Biol. Chem. 268, 7799-7808) showed that although MgPPi reduces the maximum number of trinitrophenylated RLR down to about 0.5 mol/mol of S1, this half-stoichiometric modification of RLR is not the result of any heterogeneity in the primary structure of S1. However, this result conflicts with a previous report in which the half-stoichiometric trinitrophenylation has been reported to be related to Pro/Ser microheterogeneity at the 78th residue position in the heavy chain of rabbit skeletal muscle myosin. To resolve the conflict, we isolated peptides containing both the 78th residue and RLR from the two different preparations of S1, one whose RLR was trinitrophenylated in the presence of MgPPi and the other whose RLR was not trinitrophenylated in the presence of MgPPi, and then we determined the amino acid sequences of the peptides. We found the same Pro/Ser microheterogeneity at the 78th position in the peptides from these S1s and thus concluded that this microheterogeneity has no correlation to the half stoichiometric trinitrophenylation of RLR. PMID- 8349588 TI - Abnormal regulation of low density lipoprotein-sensitive events in a cholesterol transport mutant. AB - We have isolated and characterized Chinese hamster ovary cell mutants defective in the intracellular transport of low density lipoprotein (LDL)-derived cholesterol (Dahl, N. K., Reed, K. L., Daunais, M. A., Faust, J. R., and Liscum, L. (1992) J. Biol. Chem. 267, 4889-4896). Mutant 2-2, which exhibits a cholesterol transport defect indistinguishable from the Niemann-Pick C phenotype, shows impaired but not absent LDL-mediated suppression of 3-hydroxy-3 methylglutaryl (HMG)-CoA reductase activity. In parental cells, LDL suppression of HMG-CoA reductase is modulated by two mechanisms, decreased gene transcription and accelerated protein turnover. Using the chimeric protein HMGal as a reporter protein for LDL-mediated turnover and Northern blot analysis to monitor HMG-CoA reductase mRNA levels, we have dissected the contributions of these two regulatory responses to LDL-mediated suppression of HMG-CoA reductase activity. Kinetic modeling using the kinlsq program showed the following. Mutant 2-2 exhibits normal LDL-mediated acceleration of HMGal degradation, coupled with relatively abnormal regulation of mRNA. This suggests that the LDL-cholesterol signaling pathway to the nucleus is defective relative to the signal that results in HMG-CoA reductase turnover. In addition, LDL-mediated acceleration of HMGal turnover occurs well before LDL stimulation of cholesterol esterification in mutant 2-2, whereas these events occur synchronously in the parental cell line. This suggests that more than one pathway or mechanism exists for LDL-cholesterol signaling to the endoplasmic reticulum. PMID- 8349589 TI - Kinetics of ligand binding to Pseudoterranova decipiens and Ascaris suum hemoglobins and to Leu-29-->Tyr sperm whale myoglobin mutant. AB - The kinetics of binding of O2, CO, and NO to the octameric, two-domain hemoglobins of the parasitic nematodes Pseudoterranova decipiens and Ascaris suum were determined on nanosecond and picosecond time scales using flash photolysis. The two nematode hemoglobins have very similar kinetic properties. On the picosecond time scale, they exhibit an unusual behavior in showing a geminate reaction with oxygen that is biphasic and dependent on the flash intensity. The geminate reaction with NO is also faster and more complete than for sperm whale myoglobin; however, in contrast to the O2 reaction, it is homogeneous. In addition, the oxygen dissociation rate of P. decipiens hemoglobin, 0.0035 s-1, is as low as that of A. suum hemoglobin, 0.004 s-1 (Gibson, Q. H., and Smith, M. H. (1965) Proc. R. Soc. Lond. B Biol. Sci. 163, 206-214). A mutant of sperm whale myoglobin suggested by sequence alignment of the nematode hemoglobins, Leu-29- >Tyr, did not have kinetic properties similar to them. PMID- 8349590 TI - Comparative studies of cardiac and skeletal sarcoplasmic reticulum ATPases. Effect of a phospholamban antibody on enzyme activation by Ca2+. AB - Vesicular fragments of skeletal (LSR) and cardiac (CSR) sarcoplasmic reticulum were compared with the aim of defining the effect of a monoclonal phospholamban (Pl) antibody (Ab). The Pl Ab has no effect on LSR, while enhancing the Ca2+ transport rates of CSR at Ca2+ concentrations below saturation. We found no direct effect of the Pl Ab on Ca2+ binding by the ATPase in the absence of ATP. Equilibrium measurements of Ca2+ binding yield positively cooperative isotherms which are best fit with a two-interacting sites equation. LSR and CSR display nearly identical affinities for Ca2+, and no effect of the Pl Ab is observed. Taking advantage of a stable CrATP-enzyme complex, we demonstrated that the stoichiometric ratio of occluded Ca2+ to catalytic sites is 2 in either LSR or CSR and that the addition of Pl Ab does not affect the Ca2+ concentration dependence of Ca2+ occluded after equilibration of the system. Interestingly, the cooperative interaction between the two Ca2+ sites is lost in the occluded state, with only one of the two sites acquiring lumenal exposure. The concentration dependence of Ca2+ inhibition of CSR ATPase phosphorylation with Pi is also unaffected by the Pl Ab. Contrary to the lack of Pl Ab effect on reactions measured at equilibrium, enhancement of phosphorylated intermediate formation by the Pl Ab is obtained in kinetic experiments in which nonsaturating Ca2+ and ATP are added to CSR preincubated with EGTA. Therefore, Ab binding to Pl reduces specifically the activation energy for a slow transition triggered by Ca2+ binding, with consequent enhancement of overall kinetics under conditions enhancing the rate-limiting contribution of this transition. PMID- 8349591 TI - Mechanism of inactivation of S-adenosylhomocysteine hydrolase by (Z)-4',5' didehydro-5'-deoxy-5'-fluoroadenosine. AB - S-Adenosyl-L-homocysteine (AdoHcy) hydrolase, an enzyme important in the regulation of biological methylation reactions, was shown by McCarthy et al. (McCarthy, J.R., Jarvi, E.T., Matthews, D.P., Edwards, M.L., Prakash, N.J., Bowlin, T.L., Mehdi, S., and Bey, P. (1989) J. Am. Chem. Soc. 111, 1127-1128) to be inactivated by (Z)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (ZDDFA). In this study we have shown that the mechanism of this inactivation of AdoHcy hydrolase (NAD+ form) includes a rapid addition of water to the 5'-position of ZDDFA and elimination of fluoride ion, resulting in the formation of the 5' carboxaldehydes 3 and 4. The 5'-carboxaldehydes 3 and 4 are then oxidized in a slower step to the 3'-keto-5'-carboxaldehydes 5 and 6 by reduction of the enzyme bound NAD+ to NADH. Evidence in support of this mechanism includes the observation that the first step in this mechanism (i.e. elimination of fluoride ion and formation of the 5'-carboxaldehydes 3 and 4) can be catalyzed by apo AdoHcy hydrolase and the NADH form of AdoHcy hydrolase. Incubation of ZDDFA with either the apo or NADH form of AdoHcy hydrolase resulted in rapid release of fluoride ion (determined by 19F NMR) and formation of the 5'-carboxyaldehydes 3 and 4 (determined by high performance liquid chromatography). The carboxaldehydes 3 and 4 were synthesized independently and were shown to be potent inhibitors of the NAD+ form of the enzyme. When the relative first-order rates of fluoride ion release (determined by 19F NMR) from ZDDFA, NAD+ reduction to NADH, and inactivation of the NAD+ form of the enzyme were compared, the release of fluoride ion was found to be approximately 20 times faster than NAD+ reduction or enzyme inactivation. Incubation of ZDDFA with the NAD+ form of AdoHcy hydrolase was shown to afford the 3'-keto-5'-carboxaldehydes 5 and 6, which were also formed upon incubation of the enzyme with the 5'-carboxaldehydes 3 and 4. The 3' keto-5'-carboxaldehydes 5 and 6 were shown to be tightly (but not covalently) bound to the enzyme, since these products could be released by treatment of the ZDDFA-inactivated enzyme with HClO4 or other denaturing agents. PMID- 8349592 TI - Orientation of cholera toxin bound to target cells. AB - Cholera toxin (CT) consists of a pentameric B subunit that binds to specific cell surface receptors identified as ganglioside GM1 and an A subunit that activates adenylylcyclase. The A subunit consists of A1 and A2 peptides linked by a disulfide bond; A2 acts to connect A to B, whereas A1 is an ADP ribosyltransferase that modifies the alpha subunit of the stimulatory G protein (Gs). How the toxin is oriented when it binds to the cell surface and the related issue of the mechanism by which A1 gains access to Gs alpha are not known. In the present study, we used subunit-specific antibodies and their corresponding Fab fragments to assess their affects on holotoxin binding to target cells and their immunoreactivity to cell-bound toxin. Our results suggest that CT binds with A1 facing away from the membrane. Our hypothesis is further supported by the ability to assemble active CT on the cell surface of cultured human intestinal and neurotumor cells by the sequential addition of purified B and A subunits. We also observed that when cells containing bound CT were incubated at 37 degrees C, both subunits rapidly became inaccessible to their respective antibodies. We propose that the holotoxin binds with its A subunit facing away from the membrane and must enter the cell in order for A1 to be released, gain access to Gs alpha, and activate adenylylcyclase. PMID- 8349593 TI - Transduction of mitogenic activity of platelet-derived growth factor (PDGF) AB by PDGF-beta receptor without participation of PDGF-alpha receptor in vascular smooth muscle cells. AB - In cultured rat vascular smooth muscle cells, platelet-derived growth factor (PDGF) beta receptor was expressed at a high level, whereas PDGF-alpha receptor was not detected. PDGF-BB showed a high binding activity at 4 degrees C in the cells and was not displaced by PDGF-AA or -AB. This result indicates that PDGF-AB as well as PDGF-AA does not bind to the cells lacking PDGF-alpha receptor at 4 degrees C. However, at 37 degrees C, PDGF-AB bound to the cells and induced the internalization of PDGF-beta receptor. DNA synthesis was also stimulated potentially by PDGF-AB as well as PDGF-BB in the cells, although PDGF-AA was completely inactive. At 37 degrees C, PDGF-AB caused tyrosine phosphorylation of a group of proteins including PDGF-beta receptor and phospholipase C-gamma 1, but at a slower rate than PDGF-BB. At 4 degrees C, PDGF-AB did not stimulate protein tyrosine phosphorylation, whereas PDGF-BB did. A chemical cross-linking experiment showed that PDGF-beta receptor was dimerized by PDGF-AB as well as PDGF-BB. These results indicate that PDGF-beta receptor binds PDGF-AB without participation of PDGF-alpha receptor at 37 degrees C (but not at 4 degrees C), and PDGF-AB as well as PDGF-BB acts as a potent mitogen in the vascular smooth muscle cells. PMID- 8349594 TI - Cloning, nucleotide sequence, and expression of a p-hydroxybenzoate hydroxylase isozyme gene from Pseudomonas fluorescens. AB - A gene encoding for a putative isozyme of p-hydroxy-benzoate hydroxylase (PHBH) has been isolated from Pseudomonas fluorescens (ATCC 13525). A comparison of the translated amino acid sequence with that of the known PHBH from P. fluorescens revealed that the new enzyme contains 3 additional amino acids and has 73% absolute homology to the previously known enzyme; conservation of secondary and active-site structures implied that the isozyme and known enzyme share the same general tertiary structure. Subsequent expression of the isozyme in Escherichia coli produced an enzyme with a specific activity about half that of the previously characterized PHBHs from P. fluorescens and Pseudomonas aeruginosa; in addition, somewhat weaker binding affinities for both NADPH and p-hydroxybenzoate were observed. Speculations are made on the reason for the existence of the isozyme, which does not appear to be expressed routinely in P. fluorescens. PMID- 8349595 TI - OmpF-Lpp signal sequence mutants with varying charge hydrophobicity ratios provide evidence for a phosphatidylglycerol-signal sequence interaction during protein translocation across the Escherichia coli inner membrane. AB - Using inverted Escherichia coli inner membrane vesicles we have analyzed the phosphatidylglycerol dependence of translocation of an OmpF-Lpp fusion protein carrying a signal sequence with varying positive charge at the N terminus and a hydrophobic core of varying length. It is shown that there is a direct relationship between the phosphatidylglycerol requirement of translocation and the requirement within the translocation process for positive charges on the signal sequence. This provides further evidence that the negative head group of the lipid is required for functional interaction with the positively charged N terminus of the signal sequence. PMID- 8349596 TI - The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common and distinct regulatory elements and protein complexes. AB - hXBP-1 is a transcription factor of the leucine zipper (b-zip) family important in the expression of the class II major histocompatibility complex gene, DRA. Studies with mouse-human hybrids have mapped hXBP-1 hybridizing fragments to human chromosomes 5 and 22 and the frequent detection of two mRNA transcripts suggested that hXBP-1 may be a member of a small gene family. To analyze the structure and regulation of hXBP-1 further, cosmid clones from both chromosomes were isolated. Mapping and sequence analyses reveal that chromosome 22 contains the functional hXBP-1 gene while chromosome 5 contains a processed pseudogene. hXBP-1 promoter analysis has revealed that cis-active elements within the 5' untranslated region of hXBP-1 are essential for full promoter activity. One such element, hX2, is identical to the hXBP-1 target sequence in the DRA promoter. Mutagenesis of the hX2 site substantially decreases promoter activity. This element interacts with four distinct protein complexes in mature B cells and cross-competition experiments show that two of these complexes (complex 1 and complex 4) also interact with the hXBP-1 target sequence (X2) from the DRA promoter. The similarities of the hXBP-1 promoter and of the DRA promoter (the gene that the hXBP-1 protein regulates) are further emphasized by the fact that a Y box element is located 3' of both hX2 and X2. PMID- 8349597 TI - Dissection of the human acetylcholinesterase active center determinants of substrate specificity. Identification of residues constituting the anionic site, the hydrophobic site, and the acyl pocket. AB - Substrate specificity determinants of human acetylcholinesterase (HuAChE) were identified by combination of molecular modeling and kinetic studies with enzymes mutated in residues Trp-86, Trp-286, Phe-295, Phe-297, Tyr-337, and Phe-338. The substitution of Trp-86 by alanine resulted in a 660-fold decrease in affinity for acetythiocholine but had no effect on affinity for the isosteric uncharged substrate (3,3-dimethylbutylthioacetate). The results demonstrate that residue Trp-86 is the anionic site which binds, through cation-pi interactions, the quaternary ammonium of choline, and that of active center inhibitors such as edrophonium. The results also suggest that in the non-covalent complex, charged and uncharged substrates with a common acyl moiety (acetyl) bind to different molecular environments. The hydrophobic site for the alcoholic portion of the covalent adduct (tetrahedral intermediate) includes residues Trp-86, Tyr-337, and Phe-338, which operate through nonpolar and/or stacking interactions, depending on the substrate. Substrates containing choline but differing in the acyl moiety (acetyl, propyl, and butyryl) revealed that residues Phe-295 and Phe-297 determine substrate specificity of the acyl pocket for the covalent adducts. Phe 295 also determines substrate specificity in the non-covalent enzyme substrate complex and thus, the HuAChE F295A mutant exhibits over 130-fold increase in the apparent bimolecular rate constant for butyrylthiocholine compared with wild type enzyme. Reactivity toward specific butyrylcholinesterase inhibitors is similarly dependent on the nature of residues at positions 295 and 297. Amino acid Trp-286 at the rim of the active site "gorge" and Trp-86, in the active center, are essential elements in the mechanism of inhibition by propidium, a peripheral anionic site ligand. Molecular modeling and kinetic data suggest that a cross talk between Trp-286 and Trp-86 can result in reorientation of Trp-86 which may then interfere with stabilization of substrate enzyme complexes. It is proposed that the conformational flexibility of aromatic residues generates a plasticity in the active center that contributes to the high efficiency of AChE and its ability to respond to external stimuli. PMID- 8349598 TI - Co-ordinate and restricted expression of the ProXaaArg/Lys-specific GalNAc transferase and the GalNAc beta 1,4GlcNAc beta 1,2Man alpha-4-sulfotransferase. AB - Asn-linked oligosaccharides terminating with the sequence SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha (S4GGnM) are present on the glycoprotein hormones lutropin and thyrotropin, pro-opiomelanocortin, and tissue factor pathway inhibitor. The peptide motif ProXaaArg/Lys (PXR/K), which is recognized by a PXR/K-specific GalNAc-transferase, is present in each of these glycoproteins 6-9 residues NH2-terminal to an Asn glycosylation site. Both the PXR/K-specific GalNAc-transferase and a GalNAc beta 1,4GlcNAc beta 1,2Man alpha (GGnM)-4 sulfotransferase are required for synthesis of the S4GGnM sequence. Glycoproteins which do not contain the PXR/K motif but bear Asn-linked oligosaccharides terminating with GGnM or sialic acid alpha 2,3/6GGnM have also been described, suggesting a distinct GalNAc-transferase may be responsible for their synthesis. We have examined a number of tissues and cultured cell lines for the transfer of sulfate to the trisaccharide acceptor GGnM and transfer of GalNAc to oligosaccharide acceptors on protein which do, human chorionic gonadotropin (hCG), and do not, transferrin (Trf), contain the PXR/K motif. The PXR/K-specific GalNAc-transferase and the GGnM-4-sulfo-transferase are expressed in salivary gland, pituitary, lacrimal gland, kidney, and brain, and in the cell lines AtT 20, 293, SHSY5Y, and alpha T3. In contrast Bowes, EL-4, and B16L6 cell extracts transferred GalNAc to oligosaccharides acceptors on Trf but not on hCG. A number of tissues and cell lines displayed transfer of GalNAc to both hCG and to Trf suggesting that two distinct GalNAc-transferases were present. The GGnM-4 sulfotransferase was expressed in tissues and cell lines which expressed the PXR/K-specific GalNAc-transferase but not in cell lines expressing exclusively the Trf-specific GalNAc-transferase. Thus, the PXR/K-specific GalNAc-transferase and the GGnM-4-sulfotransferase are coordinately expressed in a number of tissues other than pituitary. The Trf-specific GalNAc-transferase may account for the presence of beta 1,4-linked GalNAc on glycoproteins which do not contain the PXR/K motif. PMID- 8349599 TI - Purification and properties of selenoprotein W from rat muscle. AB - Following injection with [75Se]selenite, a low molecular weight 75Se selenocysteine containing protein was purified from rat muscle. The purification procedure involved ammonium sulfate fractionation, Sephadex G-50 gel filtration, cation exchange chromatography on CM-Sephadex, and reverse phase high pressure liquid chromatography using a C-18 Vydac column. Four forms of the protein were separated by the cation exchange and reverse phase chromatography steps. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry of the four proteins revealed masses of 9550 +/- 1, 9596 +/- 1.2, 9858 +/- 1.3, and 9898 +/- 1.1 daltons. Glutamate, glycine, lysine, leucine, and valine are the major amino acids in this protein. About 0.92 g atoms of selenium was found per g mol of protein, and this selenium was present as selenocysteine. Thus, this appears to be a new selenoprotein, and we have named it selenoprotein W. PMID- 8349600 TI - Phosphorylation of the human 46-kDa mannose 6-phosphate receptor in the cytoplasmic domain at serine 56. AB - The human 46-kDa mannose 6-phosphate receptor (MPR46) is phosphorylated in its cytoplasmic domain at serine residues. Substitution of cytoplasmic serines (at positions 35 and 56) with alanine, expression of mutant receptors in baby hamster kidney cells, and phosphopeptide mapping revealed that serine 56 is phosphorylated. Mutant MPR46 and wild-type MPR46 were found to be similarly distributed between the cell surface and intracellular membranes. Phosphate incorporation in the presence of cycloheximide indicates that phosphorylation occurred on pre-existing MPR46. Similar half-lives for the wild-type and mutant receptor proteins (approximately 43 h) and the receptor-associated phosphate (1.4 h) were found. The mutant receptors were internalized at the same rate as the wild-type receptors. Expression of mutant MPR46 and wild-type MPR46 in mouse L cells deficient in 300-kDa mannose 6-phosphate receptors did not affect the sorting of newly synthesized cathepsin D to lysosomes. Phosphorylation of cytoplasmic serine 56 is therefore essential neither for stability nor for cell surface expression and transport activities of MPR46. PMID- 8349601 TI - Charge pair interactions stabilizing ferredoxin-ferredoxin reductase complexes. Identification by complementary site-specific mutations. AB - Ferredoxin reductase (Fd-reductase) supplies electrons to mitochondrial steroid hydroxylase cytochrome P450 enzymes via a [2Fe-2S] ferredoxin. Chemical labeling studies with bovine Fd-reductase have implicated Lys-243 as important in binding to bovine ferredoxin (Hamamoto, I., Kazutaka, K., Tanaka, S., and Ichikawa, Y. (1988) Biochim. Biophys. Acta 953, 207-213). We have used site-directed mutagenesis to examine the role of charged residues in this region of human Fd reductase in ferredoxin binding. Mutant proteins were expressed in Escherichia coli and were assayed for activity by ferredoxin-mediated electron transfer to cytochrome c. Replacement of Lys-242 (homologous to Lys-243 in bovine Fd reductase) with Gln and replacement of Arg-241 with Ser had little effect (2.7- and 3.6-fold increased Km, respectively). In contrast, mutants at positions 239 and 243 (R239S and R243Q) exhibited markedly lower affinity for ferredoxin (17.5- and 1,600-fold increased Km, respectively). Studies were also carried out with two ferredoxin charge mutants shown previously to have lowered affinity for Fd reductase (Coghlan, V. M., and Vickery, L. E. (1991) J. Biol. Chem. 266, 18606 18612). Comparisons of the binding of ferredoxin mutants D76N and D79N to Fd reductase mutants R239S and R243Q suggest that Arg-239 and Arg-243 of Fd reductase each interact directly with both Asp-76 and Asp-79 of ferredoxin during formation of the complex between the two proteins. These results support the hypothesis that specific electrostatic interactions involving this region are important in stabilizing the ferredoxin-Fd-reductase complex. PMID- 8349602 TI - Regulation of tyrosine phosphorylation in neutrophils by the NADPH oxidase. Role of reactive oxygen intermediates. AB - Neutrophils possess a multicomponent NADPH-oxidase that produces large quantities of superoxide, which can in turn generate other reactive oxygen intermediates. Superoxide and its dismutation product, hydrogen peroxide, are powerful oxidants. Because the activity of certain tyrosine kinases and phosphatases can be affected by their redox state, we considered the possibility that endogenously generated reactive oxygen intermediates (ROI) may alter phosphotyrosine formation and thereby function as intra- or intercellular messengers in neutrophils. Exposure of human neutrophils to exogenous oxidants such as diamide induced marked tyrosine phosphorylation of several cellular proteins. More importantly, activation of the NADPH oxidase in permeabilized neutrophils, by direct stimulation of GTP-binding proteins, also resulted in enhanced tyrosine phosphorylation. The latter was NADPH-dependent, paralleled by production of superoxide, and was inhibited by diphenylene iodonium, an inhibitor of the flavoprotein component of the oxidase. Neutrophils, from a patient with chronic granulomatous disease, which are deficient in the production of ROI, demonstrated no such phosphotyrosine accumulation. We conclude that ROI produced by the NADPH oxidase can regulate tyrosine phosphorylation in granulocytes, possibly by effects of oxidation-sensitive tyrosine kinases and/or phosphatases. PMID- 8349603 TI - Generation and characterization of a competitive antagonist of human hepatocyte growth factor, HGF/NK1. AB - Our previous studies have suggested that a derivative of hepatocyte growth factor (HGF), HGF/NK2, containing the coding sequences for the N-terminal hairpin and first two kringle domains, is sufficient to mediate high affinity binding to the HGF receptor. Here, we wished to test directly whether HGF/NK1 (N-terminal hairpin and first kringle domains) could bind the receptor and/or mediate receptor signaling. HGF/NK1 was expressed in Escherichia coli and purified to homogeneity using heparin-affinity and fast protein liquid cation-exchange chromatography. Biological characterization of HGF/NK1 showed that it can compete for binding to the HGF receptor on human lung carcinoma A549 cells and to a soluble form of the HGF receptor. HGF/NK1 is inefficient at promoting autophosphorylation of the HGF receptor, although some activity was detected at very high concentrations. HGF/NK1 fails to exhibit mitogenic properties even at very high concentrations. However, HGF/NK1 can act as a potent competitive antagonist in this assay. Our data demonstrate directly that a receptor binding determinant of HGF is located within the N-terminal 32-212 residues of HGF. HGF/NK1 will serve as a powerful tool for (i) generating neutralizing antibodies, (ii) in determining x-ray crystallographic and nuclear magnetic resonance structures, and (iii) for in vivo studies as an HGF antagonist. PMID- 8349604 TI - Polyamine-like actions of peptides derived from conantokin-G, an N-methyl-D aspartate (NMDA) antagonist. AB - Conantokins-T and -G are highly conserved polypeptides derived from Conus venoms. The N-methyl-D-aspartate (NMDA) antagonist properties of these compounds have been attributed to a potent noncompetitive inhibition of polyamine responses. Substitution of the highly conserved gamma-carboxyglutamate residues as well as modification of the N and C termini of conantokin-G abolished the inhibition of polyamine responses at the NMDA receptor complex. However, several of these modified polypeptides closely mimicked the neurochemical profile of polyamines at the NMDA receptor complex. One of these derivatives, Tyr0-conantokin-G, was found to be the most potent compound exhibiting polyamine-like actions at the NMDA receptor complex described to date, approximately 7-fold more potent than spermine. Circular dichroism studies demonstrate a significant alpha-helical content in conantokin-G (27% in aqueous medium). However, this alpha-helicity is not sufficient for the NMDA antagonist action of the parent peptide and is neither necessary nor sufficient for the polyamine-like behavior of several conantokin-G analogs. The modified conantokin-G derivatives described in this report should be useful probes for examining the role of both polyamines and the polyamine recognition site in the operation of the NMDA receptor complex. PMID- 8349605 TI - Molecular cloning and characterization of cDNAs for the gamma- and epsilon subunits of mitochondrial F1F0 ATP synthase from the sweet potato. AB - Mitochondrial F1F0 ATP synthases purified from dicotyledonous plants contain six different subunits named alpha, beta, gamma, delta, delta', and epsilon. Our previous N-terminal amino acid sequence analyses indicated that the gamma- and epsilon-subunits of the sweet potato mitochondrial F1 correspond to the gamma- and epsilon-subunits of animal mitochondrial F1, respectively (Kimura, T., Nakamura, K., Kajiura, H., Hattori, H., Nelson, N., and Asahi, T. (1989) J. Biol. Chem. 264, 3183-3186). A cDNA clone for the gamma-subunit of the sweet potato mitochondrial F1 was identified by oligonucleotide hybridization selection of a cDNA library, and a cDNA clone for the epsilon-subunit was isolated by reverse polymerase chain reaction and hybridization selection of a cDNA library by the polymerase chain reaction product. The 1.4-kilobase long cDNA for the gamma subunit contained a 978-base pair open reading frame coding for a precursor for the gamma-subunit. The mature gamma-subunit is composed of 281 amino acids, and its sequence showed significantly higher similarities with the gamma-subunit of animal mitochondrial F1 and bacterial F1 compared with the gamma-subunit of chloroplast CF1 from plants. The precursor for the gamma-subunit contained N terminal presequence of 45 amino acid residues. By contrast, the 0.46-kilobase long cDNA for the epsilon-subunit contained a coding sequence of 207-base pairs for the mature epsilon-subunit of 69 amino acid residues that is preceded by an ATG codon suggesting that the epsilon-subunit is synthesized without the cleavable presequence for mitochondrial import. The amino acid sequence of the epsilon-subunit of sweet potato mitochondrial F1 showed similarities of 25 and 36% amino acid positional identity with the epsilon-subunits of mitochondrial F1 from yeast and bovine, respectively. PMID- 8349607 TI - A point mutation of alanine 163 to threonine is responsible for the defective secretion of high molecular weight kininogen by the liver of brown Norway Katholiek rats. AB - To clarify the mechanism of the secretion defect of high molecular weight kininogen (HK) and low molecular weight kininogen (LK) by the liver of Brown Norway (B/N) Katholiek rats causing plasma kininogen deficiency, we cloned cDNAs for HK from cDNA libraries of the livers of B/N Katholiek and B/N Kitasato rats. A point mutation of G to A at nucleotide 487 was found in the cDNA of B/N Katholiek rats by sequence analysis of the cDNAs (including the entire HK-coding region) obtained from both strains. Both B/N Katholiek and B/N Kitasato rat cDNA fragments were introduced into a eukaryotic vector, pRc/CMV, to construct their respective expression plasmid, which was used to transfect COS-1 cells. At 24 h of incubation, the culture medium of COS-1 cells transfected with the B/N Katholiek rat cDNA contained only 10% of the HK antigen that was found in COS-1 cells transfected with the B/N Kitasato rat cDNA. More HK antigen was retained in the former cells. Moreover, cells transfected with B/N Katholiek rat cDNA, in which the A at nucleotide 487 was artificially replaced by G, secreted a significant amount of HK into the medium. These results suggest that a point mutation of G to A at nucleotide 487, which causes a substitution of Ala163 to Thr in the heavy chain of HK and LK, is responsible for the defective secretion of HK and LK by the liver of B/N Katholiek rats. PMID- 8349606 TI - Effect of tethered peptidylchloromethylketone inhibitors on thermal stability and domain interactions of urokinase and other serine proteases. AB - The melting of several serine proteases that had been reacted with different peptidylchloromethylketone (cmk) inhibitors was studied by fluorescence spectroscopy and calorimetry. These inhibitors, which cross-link the two domains of the proteases, invariably increased the melting temperature by as much as 28.5 degrees C. The magnitude of the effect was dependent on the size and composition of the peptide moieties. The delta G of unfolding of tosyl-Phe-cmk-chymotrypsin was 13.5 kcal/mol compared to only 8.3 kcal/mol for chymotrypsin. Binding of cmk inhibitors also protected the two interacting domains of urokinase from acid induced decooperation and caused them to merge into a highly cooperative structure upon refolding at low pH. Fluorescence-detected melting curves of Glu Gly-Arg-cmk-urokinase indicated that unfolding/refolding at pH 4.5 is characterized by dramatic hysteresis; the cooling curves fell close to those obtained upon heating or cooling of the uninhibited enzyme. Upon second heating, the melting curves were similar to those of the original. The hysteresis effects are interpreted as follows. The tethered tripeptide binds to the active site, causing the protein to melt at much higher temperature in a single cooperative step, as if the two domains are merged into one cooperative unit. Upon cooling, the unfolded protein, with the inhibitor still attached, refolds at the same temperature as the underivatized protein. Only after the native structure is formed does the peptide moiety again bind and stabilize toward a second heating. At lower pH, second heating produced biphasic or triphasic melting curves that were attributed to differential protonation of acid-titratable groups on the enzyme and/or inhibitor at the time of refolding. Similar effects were observed with other trypsin-like proteases, indicating that the hysteresis and bi- and triphasic refolding at low pH are rather general for this class of enzyme. PMID- 8349608 TI - Rapid activation of GLUT-1 glucose transporter following inhibition of oxidative phosphorylation in clone 9 cells. AB - Exposure of Clone 9 cells to inhibitors of oxidative phosphorylation results in a rapid and striking stimulation of facilitated glucose transport (7.5-fold at 2 h) that is mediated by the GLUT-1 transporter. We have previously shown that this rapid stimulation of glucose transport occurs in the absence of any detectable increase in cell GLUT-1 or GLUT-1 mRNA content. To determine whether this early enhancement of transport is attributable to a translocation of glucose transporters to the plasma membrane, or instead to an activation of transporters already present in the plasma membrane, we have employed four different approaches to determine whether the stimulation of transport is accompanied by a corresponding increase in plasma membrane GLUT-1 sites: 1) immunofluorescence microscopy; 2) quantitation of GLUT-1 sites in plasma membrane fractions isolated by differential centrifugation and subsequent Western blotting; 3) cell surface biotinylated followed by isolation of plasma membranes and quantitation of GLUT-1 sites by Western blotting; and 4) quantitation of GLUT-1 sites in plasma membrane fractions by [3H]cytochalasin B binding. Each of these experimental approaches led to the same conclusion, namely that the large stimulation of glucose transport observed during the early phase of the response to azide is associated with only a slight increase in the abundance of GLUT-1 sites in the plasma membrane. These results strongly suggest that activation of GLUT-1 sites pre existing in the plasma membrane is the dominant mechanism mediating the early glucose transport response to inhibition of oxidative phosphorylation. PMID- 8349609 TI - Lipopolysaccharide stimulates both nuclear localization of the nuclear factor kappa B 50-kDa subunit and loss of the 105-kDa precursor in RAW264 macrophage like cells. AB - Nuclear factor kappa B (NF-kappa B) is an important regulator of gene expression in cells of the immune system. One such gene, tumor necrosis factor, is induced by bacterial lipopolysaccharide (LPS) in macrophages, and this induction has been shown to be mediated in part by NF-kappa B activation in murine macrophages. In this study, immunochemical analysis was used to follow LPS activation of the NF kappa B 50-kDa subunit in the RAW264 macrophage-like cell line. The recombinant NF-kappa B 50-kDa subunit was used as an immunogen to produce a rabbit antiserum, which was then affinity-purified using a portion of the NF-kappa B 50-kDa subunit that does not have homology to other members of the c-rel gene family. Untreated macrophages had little NF-kappa B in the nucleus as detected by Western immunoblotting. The protein was predominantly localized in the cytoplasmic fraction. Interestingly, NF-kappa B was found as the 50-kDa mature protein and 105-kDa precursor. After LPS treatment, there was a rapid nuclear translocation of NF-kappa B as detected by immunoblot analysis. There was also a rapid decrease in the amount of the cytoplasmic 105-kDa protein. This may indicate that the 105 kDa protein is a reservoir for the 50-kDa protein and that one of the actions of LPS is to increase the rate of 105-kDa precursor processing. PMID- 8349610 TI - Activation of dynamin GTPase by acidic phospholipids and endogenous rat brain vesicles. AB - Dynamin is a GTPase thought to play a role in endocytosis based on genetic analysis of its homolog in Drosophila melanogaster shibire. Previous studies have stressed an in vitro association with microtubules, though additional evidence suggests that dynamin associates with membranous organelles. In an analysis of the enzymatic and membrane binding properties of dynamin, we have found that the acidic phospholipids, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol, are able to stimulate GTP hydrolysis in a manner similar to activation previously shown with microtubules. A neutral phospholipid, phosphatidylcholine, had no effect on dynamin GTPase. Activation of dynamin was biphasic, with a decrease in activity back to basal levels with increased concentrations of either microtubules or liposomes. A comparison between GTPase stimulation induced by microtubules and that by phospholipids suggests that ionic interactions between the basic C-terminal domain of dynamin and the negatively charged microtubule or phospholipid head group are important. In support of this, GTPase stimulation by these agents in combination was not additive. A salt extracted membrane fraction from brain tissue also activated dynamin GTPase, though to a lower extent than pure phospholipids. These results suggest that membrane components could be responsible for some aspects of the regulation of dynamin function in vivo. PMID- 8349611 TI - Isolation and heterologous expression of cloned cDNAs for two rabbit nasal microsomal proteins, CYP2A10 and CYP2A11, that are related to nasal microsomal cytochrome P450 form a. AB - Nasal microsomal P450 form a (NMa), a major cytochrome P450 isozyme in rabbit olfactory and respiratory nasal mucosa with high activity toward a variety of odorants and environmental toxicants, was previously purified to electrophoretic homogeneity from rabbit nasal microsomes. In the present study, a cDNA library constructed from poly(A)+ RNA from rabbit respiratory nasal mucosa was screened with antibodies to P450 NMa, and five immunopositive clones were isolated and characterized. Sequence analysis indicated that the clones encode two highly similar P450s that contain 494 amino acid residues, with the first 20 corresponding to P450 NMa, and differ from each other in only 8 residues scattered throughout the polypeptide chains. On the basis of structural homology the two proteins are designated as CYP2A10 and CYP2A11 and are the first members of the P450 2A subfamily to be identified in nasal tissue. Genomic blot analysis indicated that 2A10 and 2A11 are apparently not allelic variants. Both genes are expressed in liver and lung as well as in nasal tissues, as judged by RNA blot analysis, but the relative levels of the two mRNAs differ. Both enzymes were partially purified after expression of the cDNAs in Escherichia coli and shown to catalyze the oxygenation of a variety of substrates, including ethanol and procarcinogens such as N-nitrosodiethylamine and phenacetin. P450 2A10 is generally more active than P450 2A11 and strikingly so in the conversion of testosterone to androstenedione. PMID- 8349612 TI - Structural organization and genomic sequence of mouse syndecan-1 gene. AB - Syndecan-1 is an integral membrane proteoglycan, which binds several extracellular matrix components and growth factors. Its expression follows morphogenetic rather than histological patterns during embryonic development and is regulated by epithelial-mesenchymal interactions during organogenesis. Malignant transformation has been shown to suppress syndecan-1 expression. In order to understand better the regulation of syndecan-1 expression, we have determined the structural organization of mouse syndecan-1 gene. Several genomic clones were isolated, covering the entire 23-kilobase (kb) syndecan-1 gene. All five exons, four introns, and the 5'- and 3'-flanking regions were sequenced. The first intron was very long (17,582 base pairs (bp)) if compared with the others that were only a few hundred nucleotides in length. The first exon contained only the signal sequence and exons II-IV all the glycosaminoglycan binding sites. The fifth exon resided both transmembrane and cytoplasmic domains, which are known to be conserved among the members of the syndecan family. This genomic structure explains why these members could have heterologous extracellular domains and homologous transmembrane and cytoplasmic domains. Syndecan-1 gene was shown by primer extension analysis to have three transcription initiation sites which were confirmed by polymerase chain reaction. These initiation sites were found to locate -217, -266, and -591 bp from described cDNA (Saunders, S., Jalkanen, M., O'Farrell, S., and Bernfield, M. (1989) J. Cell Biol. 108, 1547-1556). Within the 5'-end of the gene a 2000-bp-long CpG nucleotide-rich sequence resembling a CpG island was found, which started from the transcription initiation sites and ended in the first intron. At the 3'-end of the gene an other polyadenylation signal sequence was revealed 638 bp downstream from the first one. The two mRNAs (2.6 kb and 3.4 kb) were shown to be produced by alternative polyadenylation. PMID- 8349613 TI - Self-assembly and calcium-binding sites in laminin. A three-arm interaction model. AB - Laminin, a four-arm glycoprotein, polymerizes in vitro into networks similar to those found in basement membranes. We have dissected this calcium-dependent assembly by analyzing proteolytic fragment binding using equilibrium gel filtration, ultracentrifugation, and electron microscopy. The cathepsin G fragment C1-4 (three short arms) was found to aggregate with a critical concentration similar to that for laminin. Like laminin polymerization, this assembly was inhibited by the smaller elastase short arm fragments E4 (B1 domains VI and V) and E1' (A-B2 short arm complex). Fragment E4 bound directly to E1' in a calcium-dependent manner (KD = 1.4 microM). In contrast, homologous self interactions of short arm fragments and all interactions of long arm fragments were considerably weaker or nonexistent. While electron micrographs of E1' or E4 alone contained mostly monomers, those of E1'/E4 mixtures contained dimers and oligomers with E1' dimers connected to each other through their A and B2 arms, often with visible E4 molecules at their junctions. 45Ca2+ bound principally to fragment E1' with localization to the end of the B2 chain. These data support a model in which polymerization requires the interaction of all three ligands, one from each short arm, with calcium activating assembly by binding to the B2 short arm. PMID- 8349614 TI - Identification of the major phosphorylation sites of the Raf-1 kinase. AB - Treatment of cells with various growth factors and mitogens results in the rapid hyperphosphorylation and activation of the Raf-1 kinase. To determine if phosphorylation events affect Raf-1 activity, we have initiated experiments to identify the phosphorylation sites of Raf-1. In this report, we find that Ser43, Ser259, and Ser621 are the major sites of Raf-1 which are phosphorylated in mammalian cells and in Sf9 insect cells infected with a recombinant baculovirus encoding human Raf-1. Mutant Raf-1 proteins lacking kinase activity are also phosphorylated on these sites in vivo, indicating that these phosphorylation events are not a consequence of autophosphorylation. Furthermore, we find that Thr268 is the predominant Raf-1 residue phosphorylated in in vitro autokinase assays. In addition, we have examined the biochemical activity of baculovirus expressed Raf-1 proteins containing mutations at these phosphorylation sites. In in vitro protein kinase assays Ser259 mutant proteins were 2-fold more active than wild-type Raf-1 and Ser621 mutant proteins were inactive as kinases. Analysis of the residues surrounding Ser259 and Ser621 indicates that RSXSXP may be a consensus sequence for the kinase responsible for phosphorylation of Raf-1 at these sites. Interestingly, these RSXSXP sequences are completely conserved throughout evolution in all Raf family members. PMID- 8349615 TI - Stimulation of neutrophils with a chemoattractant activates several novel protein kinases that can catalyze the phosphorylation of peptides derived from the 47-kDa protein component of the phagocyte oxidase and myristoylated alanine-rich C kinase substrate. AB - Novel protein kinases that may participate in the signal transduction pathways of neutrophils were sought by a procedure based on the ability of these enzymes to undergo renaturation and catalyze the phosphorylation of a peptide substrate fixed in a gel. We report that neutrophils contain four uncharacterized protein kinases with molecular masses of about 69, 63, 49, and 40 kDa, which are rapidly activated upon stimulation of these cells with the chemoattractant fMet-Leu-Phe. These kinases can catalyze the phosphorylation of a peptide that corresponds to residues 297-331 of the 47-kDa subunit of the NADPH oxidase system (p47-phox). A peptide that corresponds to residues 153-178 of the human myristolyated alanine rich C kinase substrate (MARCKS) protein was also a substrate for the 69- and 63 kDa kinases. The time course for the activation of these enzymes was similar to the phosphorylation of p47-phox and MARCKS in intact neutrophils. In contrast, stimulation of these cells with 4 beta-phorbol 12-myristate 13-acetate, the calcium ionophore A23187, or the combination of these agonists did not activate these enzymes. Activation of the 63- and 40-kDa protein kinases was blocked by pertussis toxin, calyculin A, and staurosporine. Several other unidentified protein kinases were also active with these peptides but did not exhibit enhanced activity after cell stimulation with this method. PMID- 8349616 TI - Site-specific methylation inhibits transcriptional activity of platelet-derived growth factor A-chain promoter. AB - Expression of the platelet-derived growth factor (PDGF) A-chain gene is temporally and spatially restricted in development and highly regulated in selected normal and tumor cell lines. Because DNA methylation appears to be important in regulating tissue specific gene expression, we tested the influence of in vitro methylation of the human PDGF A-chain promotor on its activity in vivo in transient transfection assays. We now report that PDGF A-chain promoter activity is strongly repressed by DNA methylation in a DNA sequence-specific manner and that the repression of promoter activity by methylation requires a methyl CpG-binding protein(s). We also report that incubation of HeLa cells with 5-azacytidine sharply increases levels of endogenous PDGF A-chain gene transcripts. These results indicate that the promoter activity of the PDGF A chain gene is sharply and selectively reduced by in vitro DNA methylation and that DNA methylation in vivo also may reduce its function in selected cell lines. PMID- 8349617 TI - Cell type-specific regulation of SL-1 and SL-2 genes. Induction of the SL-2 gene but not the SL-1 gene by human keratinocytes in response to cytokines and phorbolesters. AB - The stromelysin-2 (SL-2) gene is transcriptionally active in normal human keratinocytes and encodes a secreted, catalytically competent but latent matrix metalloproteinase. Phorbolester induction resulted in the emergence of SL-2 (but not SL-1 transcripts), whereas the opposite was true for human mucosal fibroblasts. Expression of keratinocyte SL-2 was also induced by the two keratinocyte growth factors, transforming growth factor-alpha and epidermal growth factor, by the proinflammatory cytokine, tumor necrosis factor-alpha, but, somewhat surprisingly, not by interleukin-1 beta. The latent SL-2 proenzyme was isolated from 12-O-tetradecanoylphorbol-13-acetate-induced keratinocytes by immunoaffinity chromatography using a cross-reactive antibody raised against human SL-1. This procedure led to the recovery of a single M(r) 54,000 molecular species at a level of approximately 0.2 microgram/ml of culture medium. Amino terminal sequencing identified the protein as SL-2 and verified the predicted signal sequence cleavage site. Conformational activation of latent SL-2 precursor by SDS gave rise to a full-length, uncleaved (M(r) 54,000) active form and at the same time exposed a cryptic thiol group. By contrast, organomercurial activation resulted in autolytic truncation of the molecule with loss of M(r) approximately 10,000 propeptide. SL-2 shared with (human fibroblast) SL-1 the ability to cleave casein, to "superactivate" fibroblast type procollagenase, and to form apparently binary, SDS-resistant complexes with tissue inhibitor of metalloproteinases-1. PMID- 8349618 TI - Molecular and biochemical characterization of herbicide-resistant mutants of cyanobacteria reveals that phytoene desaturation is a rate-limiting step in carotenoid biosynthesis. AB - Mutant strains of the cyanobacterium Synechococcus sp. PCC 7942 that are resistant to the herbicides norflurazon and fluridone were analyzed. These herbicides inhibit phytoene desaturase, a key enzyme in the carotenoid biosynthetic pathway. In three mutants the phenotype was related to specific point mutations in pds, the gene encoding phytoene desaturase. Since the resistance was manifested in a cell-free carotenogenic assay, it is evident that the predicted amino acid changes in the target protein alter the enzyme-herbicide interactions. In addition, the mutations also reduced the in vitro activity of phytoene desaturase. Increased levels of the substrate phytoene, accompanied by a reduction in colored carotenoids, were detected in cells of each of the mutant strains. A correlation was established between the degree of increase in the steady-state levels of phytoene and the extent of reduction in total carotenoid content in the cells. These two phenomena in turn are correlated with the rate of enzymatic activity of phytoene desaturase that was measured in vitro. Hence we deduce that phytoene desaturation is a rate-limiting step in carotenogenesis in cyanobacteria. Support for this conclusion is obtained from analysis of cells of an additional mutant strain, which overexpress phytoene desaturase due to a deletion mutation in the promoter region of pds. Cells of this mutant contained more colored carotenoids than the wild-type and were resistant to herbicides that inhibit phytoene desaturase. PMID- 8349619 TI - Tumor-specific overexpression of a novel keratinocyte lipid-binding protein. Identification and characterization of a cloned sequence activated during multistage carcinogenesis in mouse skin. AB - Differential screening of cDNA libraries from chemically induced malignant mouse skin squamous cell carcinomas (SCCs) identified sequences, including one called mal1, that were up-regulated in their expression at both the benign papilloma and the malignant SCC stages during tumor development. The mal1 plasmid cDNA clone was used to screen lambda phage cDNA libraries made from chemically induced papillomas and SCCs. Two size classes (655 and 933 nucleotides excluding the poly(A) tail) of full-length cDNAs were isolated. The corresponding mRNAs differ in their 3'-untranslated region by 278 nucleotides as a result of utilizing two alternative polyadenylation signals. Both transcripts were expressed simultaneously, showing the same expression patterns, with the smaller one being the predominant species. Most tissues examined showed a weak expression of mal1 mRNA. High levels of mal1 transcripts could be detected in adipose and mammary tissues and tongue epithelia and predominantly in epidermis. The expression observed in epidermis was up-regulated dramatically during tumor formation. Computer-assisted sequence analysis revealed one open reading frame that encoded a protein of 135 amino acid residues with extensive homology to members of the lipid-binding protein family. Residues determining the proposed beta-clam structure of these proteins and the structure of the lipid-binding region were shown to be conserved in the mal1 gene. In vitro translation of mal1 RNA yielded a polypeptide of the predicted size of 15 kDa that was immunoprecipitable with an anti-rat liver fatty acid-binding protein antiserum. Based on the sequence analysis and antigenic properties of mal1, we conclude that it encodes a novel member of the lipid-binding protein family. PMID- 8349620 TI - Differential effect of brefeldin A on the biosynthesis of heparan sulfate and chondroitin/dermatan sulfate proteoglycans in rat ovarian granulosa cells in culture. AB - The subcellular localization of the enzymes involved in the glycosylation of proteoglycans was studied in rat ovarian granulosa cells by interfering with the normal traffic in the Golgi apparatus using brefeldin A. Cell cultures were metabolically labeled with [35S] sulfate and [3H]glucosamine, and the radiolabeled macromolecules were analyzed by ion-exchange and gel chromatography in combination with chondroitinase or heparitinase treatment. In the absence of brefeldin A, the cells synthesized both dermatan sulfate proteoglycans (DSPGs) and heparan sulfate proteoglycans (HSPGs) which were isolated from the culture medium, the plasma membrane, and intracellular compartments. However, in the presence of brefeldin A, the synthesized proteoglycans were almost exclusively HSPGs and were found only in the intracellular compartment. Analyses of HSPGs synthesized in the presence of brefeldin A indicated that: (i) the HS chains are synthesized on the same core protein as for the normal HSPGs, (ii) the chains are two to three times the normal molecular size; and (iii) a significant proportion of the HS chains are normally sulfated. Brefeldin A induces a disassembly of the proximal part of the Golgi complex, resulting in a redistribution of cis-, medial , and trans-Golgi resident enzymes back to the endoplasmic reticulum (ER), and blocks the transport of proteins to the trans-Golgi network. Our results indicate that the complete set of enzymes involved in the biosynthesis of HS chains are localized in the ER/proximal part of the Golgi complex, whereas the enzymes involved in the elongation/sulfation of DS chains are exclusively located in the trans-Golgi network. Furthermore, our results indicate that the enzymes involved in the biosynthesis of HS chains are specific to HS core proteins, since no DS core proteins were substituted with HS chains in the presence of brefeldin A. PMID- 8349621 TI - Expression of alternatively spliced epidermal growth factor-like domains in aggrecans of different species. Evidence for a novel module. AB - The carboxyl-terminal globular domain of human aggrecan has been shown previously to contain an alternatively spliced epidermal growth factor (EGF)-like module. We have used reverse transcription/polymerase chain reactions on cartilage-derived RNAs to investigate the heterogeneity in the EGF-like domain content of aggrecans from five species (mouse, rat, dog, bovine, and human). A novel alternatively spliced EGF-like module was detected in human aggrecan, establishing the presence of two of these domains. Highly homologous domains are present in aggrecans of other species, and the expression of these modules is identical (4-8%). They share significant homology with EGF-like domains of differentiation proteins and coagulation factors and have a putative calcium binding site. In contrast to this novel domain (EGF2), the previously described EGF-like module (EGF1) is expressed at a high level exclusively in human aggrecan. The expression of the two EGF-like domains in human aggrecan appears to be independent. Although the function of these domains is not understood, the uniform expression of the EGF2 domain may indicate a general role of this aggrecan module, while the expression of the EGF1 domain may reflect species specificity. PMID- 8349622 TI - Specific nuclear protein binding to a negative regulatory element on the human CYP1A1 gene. AB - Employing reporter gene/CYP1A1 chimeric plasmids, we previously identified a 275 base pair (bp) cis-element (-833 to -558; NRE275) that down-regulated the CYP1A1 promoter. In the present study, this negative regulatory activity was further localized to two subfragments of 105 bp (-833 to -728; NRE105) and 170 bp (-728 to -558; NRE170), each of which exhibited activity with a heterologous promoter/enhancer. Co-transfection studies demonstrated a dependence on cellular trans-acting factors present at limiting concentrations. Electrophoretic mobility shift assays revealed the presence of protein(s) that specifically bound to NRE275, NRE105, and NRE170. Based upon competition studies, the protein(s) that bound to NRE105 appeared to recognize sites similar to those recognized by the NRE170-binding proteins. DNase I footprint analysis of NRE105 demonstrated nuclear protein binding to a 21-bp palindrome (-794 to -774). Protection was also observed along conserved guanine/cytosine-rich sequences that flank the palindrome, but in a strand-specific manner. Guanine residues involved in protein binding were identified by methylation interference experiments. Based on transient expression assays with each of the three NRE105 components, all three appear to be necessary for complete negative regulatory activity. However, it is clear the palindrome is the most important sequence with the guanine/cytosine rich elements playing an ancillary role. PMID- 8349624 TI - Copurification of casein kinase II with 20 S proteasomes and phosphorylation of a 30-kDa proteasome subunit. AB - The 20 S proteasome is a multicatalytic protease that has been implicated in several processes including ATP/ubiquitin-dependent proteolysis. However, the ATP requirement(s) related to proteasome function is undefined. We demonstrate that a protein kinase activity copurifies through multiple steps utilized to isolate latent 20 S proteasomes from human erythrocytes. The kinase phosphorylates serine residues within a single 30-kDa proteasome subunit. The activity is not sensitive to cyclic AMP or protein kinase inhibitor, indicating that it is not a cyclic AMP dependent kinase. It is sensitive to nanomolar levels of heparin and is able to utilize both ATP and GTP as phosphodonors, similar to casein kinase II activity. Moreover, a polyclonal antibody specific for casein kinase II recognizes the alpha' subunit of casein kinase II in the 20 S preparation and specifically immunoprecipitates the proteasome-phosphorylating activity. These characteristics suggest that the proteasome kinase is similar or identical to casein kinase II. It is suggested that phosphorylation of the 30-kDa proteasome subunit by casein kinase II may be involved in regulating the activity and/or assembly of proteasome complexes. PMID- 8349623 TI - Thromboxane A2 stimulates vascular smooth muscle hypertrophy by up-regulating the synthesis and release of endogenous basic fibroblast growth factor. AB - We have shown previously that thromboxane A2 stimulates hypertrophy of cultured rat aortic smooth muscle cells defined as protooncogene expression and protein synthesis without DNA synthesis or cellular proliferation (Dorn, G.W., II, Becker, M.W., Davis, M.G. (1992) J. Biol. Chem. 267, 24897-24905). Since endogenous growth modulators could possibly regulate vascular smooth muscle growth to this vasoconstrictor, we tested the hypothesis that thromboxane stimulated vascular smooth muscle hypertrophy was due to increased expression of endogenously produced basic fibroblast growth factor (bFGF). The thromboxane mimetic (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619) (1 microM) increased cultured rat aorta derived smooth muscle cell immunoreactive bFGF content by 331 +/- 40% over untreated controls after 24 h. Co incubation of vascular smooth muscle cells with a specific antisense oligodeoxynucleotide (AS) against codon 60 of bFGF coding sequence reduced thromboxane-stimulated bFGF expression by 72 +/- 5% and prevented thromboxane stimulated hypertrophy (nonsense oligonucleotide had no effects). Addition of exogenous bFGF (20 ng/ml) restored growth to AS-treated/thromboxane-stimulated vascular smooth muscle cells. Furthermore, addition to the culture medium of neutralizing antibody against bFGF inhibited U46619-stimulated vascular smooth muscle hypertrophy by 69 +/- 17%, whereas nonimmune IgG had no effect. Since protein tyrosine phosphorylation is a cell signal associated with growth, thromboxane-stimulated tyrosine phosphorylation was also examined. Exposure to 1 microM U46619 for 10 min increased vascular smooth muscle immunoreactive phosphotyrosine content of 130-144-, 86-, 80-, 75-, and 58-kDa proteins. The tyrosine kinase inhibitor herbimycin A (5 microM) prevented thromboxane stimulated tyrosine phosphorylation, but not thromboxane-stimulated hypertrophy, suggesting that tyrosine phosphorylation was not required for thromboxane stimulated vascular smooth muscle growth. These results indicate that increased expression and release of endogenous bFGF, but not direct tyrosine phosphorylation, mediates the hypertrophic vascular smooth muscle response to thromboxane. PMID- 8349625 TI - Preferential formation of C3b-IgG complexes in vitro and in vivo from nascent C3b and naturally occurring anti-band 3 antibodies. AB - Naturally occurring anti-band 3 antibodies appear to have tissue homeostatic functions in the clearance of senescent red cells and in eliciting selective phagocytosis of oxidatively stressed red cells by mediating C3b deposition under conditions that favor the alternative complement pathway (Lutz, H. U., Bussolino, F., Flepp, R., Fasler, S., Stammler, P., Kazatchkine, M. D., and Arese, P. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 7368-7372). They overcome the notoriously low affinities of naturally occurring antibodies by having affinity for C3 which renders these antibodies preferred targets of nascent C3b. Anti-band 3 antibodies preferentially formed covalently linked C3b-IgG complexes, when C3 was activated randomly by trypsin. IgG depleted of anti-band 3 antibodies had almost lost the ability to form C3b-IgG complexes. Likewise, anti-band 3 antibodies, but not anti spectrin antibodies, preferentially formed C3b-IgG complexes on oxidatively stressed red cells in the presence of a 10(3)-fold excess of other serum IgG, when complement deposition was initiated by antibody binding in diluted serum. Moreover, anti-band 3 antibodies preferentially formed C3b-IgG complexes at a 10(5)-fold excess of other IgG on in vivo aging red cells, since C3b-IgG complexes from senescent red cells contained exclusively anti-band 3 antibodies with an affinity for C3. Thus, the low titer, low affinity naturally occurring antibody became functionally relevant by preferred generation of C3b-IgG complexes that can nucleate alternative complement pathway C3 convertases and represent the most effective opsonins (Fries, L. F., Siwik, S. A., Malbran, A., and Frank, M. M. (1987) Immunology 62, 45-51). PMID- 8349626 TI - Adenovirus DNA polymerase is phosphorylated by a stably associated histone H1 kinase. AB - Adenovirus DNA polymerase (AdPol) exists as a complex with the preterminal protein (pTP) and is essential for both initiation and elongation stages of viral DNA replication. Recent evidence from our laboratory indicates that AdPol is a phosphoprotein and that the major in vivo phosphorylation site, serine 67, occurs within the consensus substrate recognition sequence for cdc2 kinases. In this study, we found that a protein kinase which also exhibits histone H1 phosphorylation activity is stably associated with AdPol. AdPol forms a multimeric complex with this histone H1 kinase and pTP in HeLa cells infected with adenovirus or coinfected with recombinant vaccinia viruses encoding AdPol and pTP. The associated protein kinase and the p34cdc2 kinase phosphorylate AdPol at the same sites which are utilized in vivo, suggesting that the p34cdc2 kinase or a related kinase may be involved in the in vivo phosphorylation of AdPol. Serine 67 is also one of the major in vitro phosphorylation sites, and the substitution of alanine for serine at this position abolishes DNA replication initiation activity of AdPol. PMID- 8349627 TI - The human S mu bp-2, a DNA-binding protein specific to the single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region. AB - We have cloned the cDNA encoding the human homologue of S mu bp-2, which binds to single-stranded DNA with 5'-phosphorylated guanine-rich sequences related to the immunoglobulin mu chain switch (S mu) region. The deduced amino acid sequences of the mouse and human S mu bp-2 are 76.5% homologous and contain motifs conserved among helicases. We have identified a domain essential for DNA binding at residues 638-786. The binding domain is less conserved (63% homologous) than the putative catalytic domain of N-terminal half containing most of the helicase motifs (85% homologous). The human and mouse S mu bp-2 have similar, although slightly different, binding specificities. Although the mouse S mu bp-2 preferentially binds to the mouse S mu motif (GGGGT), the human S mu bp-2 binds equally well to the human (GGGCT) and mouse S mu motifs. The human S mu bp-2 gene was mapped to chromosome 11 q13.2-q13.4 by in situ hybridization. PMID- 8349628 TI - Cytokine regulation of low density lipoprotein receptor gene transcription in HepG2 cells. AB - Elevated plasma levels of cytokines have been demonstrated in inflammatory, malignant, and infectious diseases. These disease states are often associated with abnormal lipid metabolism and reductions in plasma cholesterol levels. To determine if inflammatory cytokines could influence hepatic lipid metabolism, we evaluated low density lipoprotein (LDL) receptor function and gene expression in cytokine stimulated HepG2 cells, a hepatoblastoma-derived cell line which shares many functional similarities with normal hepatocytes. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1) increased LDL binding to HepG2 cells in a dose-responsive manner. Other cytokines including macrophage-colony stimulating factor, granulocyte macrophage-colony stimulating factor, and gamma-interferon had no significant effects on LDL binding. Increased binding in response to TNF or IL-1 was paralleled by increased steady-state levels of LDL receptor mRNA. Evaluation of LDL receptor mRNA half-life revealed no significant change in mRNA stability between control and TNF- or IL-1-stimulated cells. A fusion gene construct consisting of 1563 base pairs of the 5'-flanking DNA of the human LDL receptor gene was coupled to a luciferase reporter gene, transfected into HepG2 cells, and promoter activity was assayed after TNF and IL-1 challenge to the cells. TNF and IL-1 increased promoter activity 200-400%, while treatment with LDL inhibited promoter activity by 70-85%. TNF or IL-1 co-incubation with LDL could not override transcriptional inhibition by LDL. Pretreatment with cycloheximide prevented induction of LDL receptor mRNA by TNF, but not by IL-1, suggesting stimulation of LDL receptor transcription by TNF requires protein synthesis. We propose that TNF and IL-1, acting via distinct signal transduction pathways, increase surface LDL receptors by increasing gene transcription. Our findings suggest that cytokine-induced hypocholesterolemia may be related to TNF and/or IL-1 stimulation of hepatic LDL receptor gene expression and function. PMID- 8349629 TI - Single amino acid substitutions affecting the substrate specificity of the Escherichia coli K-12 nucleoside-specific Tsx channel. AB - The Tsx protein from the Escherichia coli outer membrane is a channel-forming protein containing a nucleoside-specific binding site. The antibiotic albicidin enters the cell via this substrate-specific channel. Because albicidin is toxic for E. coli at a very low external substrate concentration, the Tsx channel is likely to contain a binding site for this antibiotic. To identify residues involved in the Tsx substrate-specific channel activity, we devised a selection scheme to isolate albicidin-resistant tsx mutants synthesizing Tsx proteins with defects in their nucleoside uptake function. We recovered seven distinct albicidin-resistant tsx alleles, six point mutations and a 39-base pair duplication. The mutants with a duplication of residues 21-33 of Tsx or with single amino acid substitutions of residue Gly28 (to Arg) and Ser217 (to Arg) are completely deficient in nucleoside uptake at a low substrate concentration. Substitutions of Phe27 to Leu, Gly28 to Glu, Gly239 to Asp, and Gly240 to Asp result in a Tsx protein partially defective in nucleoside transport. These mutant proteins still permit nonspecific diffusion of serine indicating that the mutations do not result in a block of the Tsx channel. Our results are discussed in terms of a model for the topological organization of the Tsx protein within the outer membrane of E. coli. PMID- 8349630 TI - A peptide from ICAM-2 binds to the leukocyte integrin CD11a/CD18 and inhibits endothelial cell adhesion. AB - Numerous leukocyte functions depend on adhesive intercellular interactions. The leukocyte-specific integrins CD11a/CD18 (lymphocyte function-associated antigen-1 (LFA-1)) and CD11b/CD18 (complement type 3 receptor (Mac-1)), which bind to the intercellular adhesion molecules ICAM-1 and ICAM-2, play a key role in adhesion. Little is known about the binding in molecular detail. We have now defined a peptide region from the first immunoglobulin domain of ICAM-2 that is specifically involved in binding to CD11a/CD18. A synthetic peptide from this part of ICAM-2, covering residues 21-42, bound to purified CD11a/CD18 and inhibited the adhesion of endothelial cells to this integrin. It also inhibited the binding of B lymphoblastoid cells to endothelial cells. Leukocytes bound to the peptide coated on plastic. Several shorter peptides from the same region showed less or no activity. PMID- 8349631 TI - Receptor accessory factor enhances specific DNA binding of androgen and glucocorticoid receptors. AB - Protein-protein interactions are common among transcriptional activators and may have important consequences for gene regulation. Using the mobility shift assay, we have identified a factor that enhances specific DNA binding of truncated rat androgen (AR) and glucocorticoid (GR) receptors by 25- and 6-fold, respectively, through the formation of heteromeric complexes. This factor, designated receptor accessory factor, or RAF, also potentiates DNA binding of full-length human GR. RAF is temperature and trypsin sensitive and is present in a variety of cultured mammalian cells. By gel filtration RAF has a predicted molecular mass of 130 kDa. RAF enhancement of AR-DNA binding is optimal with androgen response element DNA. RAF appears to interact directly with AR because 1) deoxycholate, which interferes with protein-protein but not protein-DNA interactions, prevents RAF.AR.DNA complex formation, 2) RAF activity is recovered from an androgen response element DNA affinity column only in the presence of AR, and 3) RAF increases the size of an AR.DNA complex by gel filtration. Mutagenesis of truncated AR fragments indicates that a region in the NH2-terminal domain is required for RAF to enhance AR-DNA binding. The interaction of RAF with AR and GR suggests that RAF might influence the ability of these nuclear receptors to activate transcription. PMID- 8349632 TI - Characterization of two allelic variants of a human pregnancy-specific glycoprotein gene. AB - The pregnancy-specific glycoproteins (PSGs) of the human placenta are a group of proteins that together with the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. To study the control of PSG expression, we isolated and characterized PSG genes and identified cis-acting DNA elements in the 5'-flanking gene regions essential for PSG expression. Two overlapping PSG cosmid clones, which contain two allelic variants of a PSG gene (PSG12 and PSG12 psi), were isolated from an unamplified library made from a single individual. Cosmid 1 contains exons 1 (5'/L) and 2 (L/N) of the PSG12 gene located downstream of a previously identified PSG1-I gene. Cosmid 6 contains a portion of the PSG1-I gene lacking exons 1 and 2 upstream of a complete PSG12 psi transcription unit. Sequence comparison indicates that exons 5'/L and L/N in PSG12 and PSG12 psi are 99% identical, except that the L/N exon in the PSG12 psi gene contains a stop codon. Both PSG12 and PSG12 psi transcripts were detected in the human placenta, indicating that both genes are actively transcribed. However, the PSG12 psi gene may represent an allelic pseudogene variant of the PSG12 gene, because all identified PSGs contain a functional N-domain. Primer extension analysis showed that the PSG12 gene starts at a cluster of sites located at -106 to -104 base pairs with respect to the translation start site. In transient transfection assays using a chloramphenicol acetyltransferase reporter gene, we demonstrated that the -835 to -34 DNA region upstream of the translation start site of PSG12 or PSG12 psi contained both positive and negative elements that control PSG expression. Deletion analysis showed that nucleotides -172 to -34 in the PSG12 gene could function as a promoter. Gel retardation analysis showed that protein factors in human placental cell extract formed four complexes (I, II, IIa, and III) with the PSG12(-172/-34) DNA. Site-directed mutagenesis that prevents protein factor binding to the PSG12 promoter resulted in a marked reduction in transcription activation, locating the core enhancers at nucleotides -148 to -141 and -60 to -55. Mutagenesis studies also showed that the ACAGC repeats at nucleotides -84 to -68 in the PSG12 5'-flanking are essential for expression of the PSG12 gene in human placental cells. PMID- 8349633 TI - Conserved cysteine residues are critical for the enzymatic function of the lymphocyte-specific tyrosine protein kinase p56lck. AB - We have evaluated the possibility that conserved cysteine residues are critical for the enzymatic function of p56lck. Through oligonucleotide-directed mutagenesis, 5 Lck residues (cysteines 217, 224, 378, 464, and 475) were individually mutated to alanines, and the effects of these substitutions were tested in various in vitro and in vivo assays. We found that mutation of either of 2 cysteines located in the carboxyl portion of the kinase domain (cysteines 464 and 475) abolished the catalytic function of Lck. In addition, it was noted that alteration of cysteine 475 resulted in a dramatic reduction of the half-life of p56lck. These cysteine residues are highly conserved throughout the tyrosine protein kinase family, suggesting that they may play important functions in catalysis and/or substrate recognition. PMID- 8349635 TI - Identification of the phosphorylated region responsible for the permissive activation of protein kinase C. AB - Protein kinase C (PKC) appears to require phosphorylation in order to function as an effector-dependent kinase (Pears, C., Stabel, S., Cazaubon, S., and Parker, P. J. (1992) Biochem. J. 283, 515-518). By site-directed mutagenesis of the PKC alpha cDNA, it has been shown that a region including 3 threonine residues (Thr 494, Thr-495, and Thr-497), present in the catalytic domain, is involved in controlling PKC activity. Substitution of these 3 threonine residues by alanine residues leads to the expression, in COS-1 cells, of an unphosphorylated protein with an apparent molecular mass of 76 kDa, similar to that determined for the primary translation product. The biochemical characterization of this PKC alpha mutant reveals that it is a functional phorbol ester-binding protein but retains no kinase activity. Coexpression of this PKC alpha mutant and wild type PKC beta demonstrates that the mutant has a dominant effect upon PKC beta phosphorylation. The location of this region and its phosphorylation in relation to PKC function are discussed. PMID- 8349634 TI - Identification of TFIID components required for transcriptional activation by upstream stimulatory factor. AB - A TATA box-binding initiation factor, TFIID, plays a central role in the transcriptional regulation by activators. Using anti-TFIID tau (a TATA box binding component of native TFIID) immunoaffinity chromatography, nine polypeptides (230, 110, 85, 62, 58, 42, 28, 22, and 21 kDa) were identified as native Drosophila TFIID components that are tightly associated with TFIID tau. To verify the functional activity of the purified TFIID complex, template DNA and other transcription factors were reconstituted with purified TFIID bound to the antibody-Sepharose matrix. Immobilized TFIID mediated not only basal transcription but transcriptional activation by upstream stimulatory factor (USF). On the other hand, recombinant TFIID tau immobilized on the same antibody Sepharose matrix could not mediate activation by USF. These results suggest that one or more of these additional polypeptides are required as functional TFIID subunits for activator-dependent transcription in conjunction with TFIID tau. As further evidence of the relevance of the Drosophila TFIID components identified in this analysis, including the previously unrecognized p230 (Dynlacht, B. D., Hoey, T., and Tjian, R. (1991) Cell 66, 563-576), protein blot analysis showed that TFIID tau interacts specifically and exclusively with p230. This suggests that p230 is an integral subunit of TFIID and that it may play a major role in tethering other subunits to TFIID tau. PMID- 8349636 TI - Mechanism of site-specific recombination. Logic of assembling recombinase catalytic site from fractional active sites. AB - The active nucleophilic species in the strand cleavage and strand exchange steps of site-specific recombination by the Flp protein are the active site tyrosine (Tyr-343) of Flp and the 5'-hydroxyl of Flp-nicked DNA, respectively. The target phosphodiester, activated by Flp, can be cleaved by an exogenous nucleophile derived, for example, from H2O2. Flp variants that are defective in the phosphate activation step and cannot sustain Tyr-343-mediated cleavage also fail to elicit H2O2-mediated cleavage. An Flp mutant lacking Tyr-343, (Flp(Y343F)), can carry out both the strand cleavage and strand exchange reactions in the presence of a age and strand exchange reactions in the presence of a tyrosine analog. These results are consistent with a cis-activation/trans-nucleophilic attack paradigm for strand breakage and strand union. The proposed model conceptually unifies the chemistry and enzymology of the two partial reactions of recombination. The mechanism of Flp action has strong implications for phosphoryl transfer reactions in other site-specific DNA recombination systems and in RNA splicing. PMID- 8349638 TI - Heterogeneity of recombinant human antithrombin III expressed in baby hamster kidney cells. Effect of glycosylation differences on heparin binding and structure. AB - To determine the effects of differences in glycosylation on the structure and functional properties of recombinant human antithrombin (rHAT), we have characterized the properties of the recombinant protein overexpressed by baby hamster kidney cells. Three forms of rHAT, I-III, were isolated which differed in affinity for heparin. Form I had the lowest affinity and contained a high proportion of highly branched complex carbohydrate. Form II had higher affinity and contained both complex and high mannose-type chains. Form III had the highest affinity and was similar to form II in the type of carbohydrate present, but had a lower level of glycosylation, consistent with the absence of carbohydrate at one of the four glycosylation sites. 1H NMR spectra of plasma HAT and rHAT forms I-III suggested very similar protein structures for all forms. Heparin pentasaccharide produced almost identical NMR perturbation difference spectra. The only functional difference found was in the rates of inactivation of factor Xa. Forms II and III gave second order rate constants similar to that of plasma HAT, whereas form I gave a biphasic inhibition, with the first phase having a rate about four times that of the other forms. We conclude that carbohydrate heterogeneity does not alter the structure of the HAT polypeptide or the heparin induced conformational change, but does affect the heparin affinity and can alter the rate of proteinase inhibition. PMID- 8349637 TI - RecA binding to bulge- and mismatch-containing DNAs. Certain single base mismatches provide strong signals for RecA binding equal to multiple base bulges. AB - Studies from several laboratories have demonstrated that RecA protein can recognize a variety of perturbations in the DNA helix. Here, using a nitrocellulose filter binding assay, it was observed that RecA bound to bulge containing DNAs more effectively than non-bulged DNA. The degree of binding of RecA protein to bulged DNA was dependent on the conformation of the bulged bases and the kinking angles produced by the bulges as determined by the type and number of bases in the bulge. Although a single base mismatch does not kink DNA, RecA protein showed preferential binding to DNAs containing certain single base mismatches. An A.C mismatch flanked by A.T base pairs in a 28-base pair (bp) DNA facilitated the binding of RecA protein to the same high level as when the 28-bp DNA contained a 4-base cytosine bulge. Chemical probing techniques were used to examine the structure of DNA within the RecA filament. It was found that upon binding of RecA protein, the DNA helix becomes accessible over at least 14 bp, and the degree of sensitivity agrees with the binding efficiency of RecA protein. PMID- 8349640 TI - Lysine 84 is at the subunit interface of lac repressor protein. AB - Mutations have been generated at the Lys84 site of the lac repressor to explore its predicted role in inducer binding and/or subunit interaction. Four single mutations, Lys84-->Ala, Lys84-->Leu, Lys84-->Arg, and Lys84-->Glu, have been generated by site-specific mutagenesis. In addition, the mutation Tyr282-->Asp, which results in a monomeric repressor, has been coupled with these four single mutants to generate the four corresponding double mutants. Unchanged inducer binding affinities in all Lys84 mutants except Lys84-->Arg suggest that Lys84 does not contribute energy to inducer binding and is not found in the inducer binding site as previously proposed (Sams, C. F., Vyas, N. K., Quiocho, F. A., and Matthews, K. S. (1984) Nature 310, 429-430). Interestingly, the double mutants with hydrophobic side chains at the Lys84 site are tetramers, while those with charged side chains remain monomers. This result agrees with the recent model of the lac repressor (Nichols, J. C., Vyas, N. K., Quiocho, F. A., and Matthews, K. S. (1993) J. Biol. Chem. 268, 17602-17612), in which Lys84 is mapped by sequence alignment to the same face of the subunit as Tyr282. More detailed inducer binding, operator binding, and immunoblotting studies show that all the mutations at Lys84 have quaternary structures that deviate from wild-type protein, providing supportive evidence for the model placing this residue on the surface of the monomer subunit. Substitution of Lys84 by Ala or Leu results in 100-200-fold decreased association and dissociation rate constants for inducer binding and biphasic character. This decrease can be rescued at least partially in the respective double mutants at elevated pH, at which wild-type repressor shows a 10-fold decrease in affinity and cooperativity in inducer binding. In all substitutions with Ala or Leu, immunoblotting patterns with monoclonal antibody, an assay sensitive to alterations in quaternary structure, are distinct from wild type repressor. Although substitution with Arg at position 84 yields a protein with 10-fold lower inducer binding affinity, the mutant shows decreased pH dependence of inducer binding. Substitution at this site with Glu results in cooperativity at neutral pH with no change in inducer binding at elevated pH. In addition, operator binding affinity of this mutant is affected by elevated pH, a phenomenon not observed in wild-type repressor. These changes in inducer and operator binding properties appear to be related to the altered quaternary structure of these mutants at Lys84. PMID- 8349639 TI - Model of lactose repressor core based on alignment with sugar-binding proteins is concordant with genetic and chemical data. AB - Using primary sequence similarity to arabinose-binding protein, D-glucose/D galactose-binding protein, and ribose-binding protein (Vyas, N. K., Vyas, M. N., and Quiocho, F. A. (1991) J. Biol. Chem. 266, 5226-5237; Mowbray, S. L., and Cole, L. B. (1992) J. Mol. Biol. 225, 155-175), the core domain (residues 62-323) of the bacterial regulatory protein lac repressor has been aligned to these sugar binding proteins of known structure. Although the sequence identity is not striking, there is strong overall homology based on two separate matrix scoring systems (minimum base change per codon (MBC/C) and amino acid homology per residue (AAH/R)) (mean score: MBC/C < 1.25, AAH/R > 5.50; random sequences: MBC/C = 1.45, AAH/R = 4.46). Similarly, the predicted secondary structure of the repressor exhibits excellent agreement with the known secondary structures of the sugar-binding proteins. Using this primary sequence alignment, the tertiary structure of the core domain of the lac repressor has been modeled based on the known structures of the sugar-binding proteins as templates. While the structure deduced for the repressor is hypothetical, the model generated allows a comparison between the predicted tertiary arrangement and the wealth of genetic and chemical data elucidated for the repressor. Important residues involved in operator and sugar binding and in protein assembly have been identified using genetic methods, and placement of these residues in the model is consistent with their known function. This approach, therefore, provides a means to visualize the core domain of the lac repressor that allows interpretation of genetic and chemical data for specific residues and rational design of future experiments. PMID- 8349641 TI - Isolation and characterization of a cDNA encoding rat liver cytosolic epoxide hydrolase and its functional expression in Escherichia coli. AB - A cDNA of 1992 base pairs encoding the complete rat liver cytosolic epoxide hydrolase has been isolated using a polymerase chain reaction-derived DNA fragment (Arand, M., Knehr, M., Thomas, H., Zeller, H. D., and Oesch, F. (1991) FEBS Lett. 294, 19-22) known to represent the 3'-end of the cytosolic epoxide hydrolase mRNA. Sequence analysis revealed an open reading frame of 1662 nucleotides corresponding to 554 amino acids (M(r) = 62,268). The DNA sequence obtained did not display significant homology to the sequences of microsomal epoxide hydrolase or leukotriene A4 hydrolase or to any other DNA included in the EMBL Data Bank (release 32). On Northern blotting of rat liver RNA, a single mRNA species was detected that was strongly induced on treatment of the animal with fenofibrate, a potent peroxisome proliferator. The most significant structure of the deduced protein is a modified peroxisomal targeting signal (Ser-Lys-Ile) at the carboxyl terminus that is regarded to be responsible for the unusual dual localization of the cytosolic epoxide hydrolase in peroxisomes as well as in the cytosol. In addition, a leucine zipper-like motif was identified at the amino terminus. Its possible implication for the observed dimeric structure of cytosolic epoxide hydrolase is discussed. The isolated cDNA was expressed in bacteria to yield a catalytically active enzyme. Specific activity of the crude lysate obtained exceeded that of rat liver cytosols from maximally induced animals by a factor of 8. PMID- 8349642 TI - Molecular cloning and expression of murine liver soluble epoxide hydrolase. AB - A clofibrate-induced mouse liver cDNA library was prepared and used to isolate the coding sequence for soluble epoxide hydrolase. A 1668-base pair (bp) clone was isolated and found to contain a 1269-bp open reading frame coding for 423 amino acids. Subsequent RNA polymerase chain reaction resulted in the isolation of 396 bp of additional 5'-sequence. Translation of the resulting 1659-bp open reading frame produced a 553-residue protein (62,527 Da) containing deduced peptide segments that matched the amino acid sequences of six peptide fragments isolated previously from CNBr digests of pure murine soluble epoxide hydrolase. Neither the DNA nor the protein sequence showed significant similarity to other currently published sequences. Structural analysis of the soluble epoxide hydrolase coding region suggested at least one potential regulatory motif. Expression of the composite cDNA in COS-7 cells resulted in a 5-10-fold increase in soluble epoxide hydrolase activity and a similar increase in soluble epoxide hydrolase protein amount compared to mock-transfected or vector control transfected cells. Treatment of C57BL/6J mice with clofibrate led to an approximately 4-fold increase in both soluble epoxide hydrolase enzyme activity and steady-state mRNA levels. PMID- 8349643 TI - Isolation and characterization of LIP5. A lipoate biosynthetic locus of Saccharomyces cerevisiae. AB - A number of mutants with pleiotropic effects on mitochondrial metabolism have been isolated in yeast Saccharomyces cerevisiae, and for many the biochemical function that is impaired is not yet known. We report here the isolation and characterization of the LIP5 gene involved in lipoic acid metabolism which complements the g189 mutant (Tzagoloff, A., and Dieckmann, C. L. (1990) Microbiol. Rev. 54, 211-225). DNA sequence analysis of complementing yeast genomic DNA revealed an open reading frame predicting a protein of 414 amino acids. The protein sequence deduced from the gene shares 43% identical residues with the product of the Escherichia coli lip gene, which codes an enzyme involved in lipoic acid synthesis. The LIP5 mutant is not capable of synthesizing lipoic acid but still possesses the activity necessary for attachment of lipoic acid to protein. Relative to the E. coli lip gene product, the LIP5 protein has an amino terminal extension with characteristics of mitochondrial targeting signals. Cells carrying a disrupted copy of the LIP5 gene show slow growth on ethanol-rich media and barely detectable growth on glycerol-rich media. Unlike other strains with defects in the tricarboxylic acid cycle, LIP5 mutants undergo a high frequency of mitochondrial DNA deletions. PMID- 8349644 TI - Separation of splicing factor SF3 into two components and purification of SF3a activity. AB - Components required for the splicing of nuclear messenger RNA precursors in vitro have been isolated from HeLa cells. Here we describe the separation of splicing factor SF3 into two components, SF3a and SF3b. Both activities are required together with several other protein factors and U1 and U2 small nuclear ribonucleoproteins for the assembly of a presplicing complex which represents the first ATP-dependent step in the assembly of the active spliceosome. SF3a has been purified to homogeneity by a combination of ion-exchange chromatography, gel filtration, and glycerol gradient sedimentation. It consists of a complex of three polypeptides of 60, 66, and 120 kDa. The association of SF3a activity with these polypeptides has been confirmed by immunoprecipitation and depletion experiments using a monoclonal antibody directed against the 66-kDa subunit. PMID- 8349645 TI - Cloning and expression of PTP-PEST. A novel, human, nontransmembrane protein tyrosine phosphatase. PMID- 8349646 TI - Modification of a free Fe-S cluster cysteine residue in the active iron responsive element-binding protein prevents RNA binding. AB - The iron-responsive element-binding protein (IRE-BP) binds to specific RNA stem loop structures called iron-responsive elements (IREs), which mediate the post transcriptional regulation of a variety of genes involved in iron metabolism. The IRE-BP is cytosolic aconitase, and a [4Fe-4S] cubane cluster is required for aconitase activity but is associated with loss of IRE binding affinity. Chemical modification of the IRE-BP can abrogate RNA binding and the 3 cysteines predicted to coordinate the Fe-S cluster in the IRE-BP could be targets for modification. We report the expression of recombinant IRE-BP in which the three putative cluster cysteines (Cys-437, Cys-503, and Cys-506) have been mutated to serine residues. Replacement of any or all of these cysteine residues results in a complete loss of aconitase activity. While all of the mutants bind RNA, substitution of Cys-437 specifically renders the IRE-BP resistant to inactivation by low concentrations of N-ethylmaleimide or diamide. These results identify Cys 437 as the target of in vitro regulation of RNA binding in the IRE-BP and suggest that, in the RNA-binding form of the protein, Cys-437 is free and therefore available for modifications that inhibit RNA binding. PMID- 8349647 TI - Targeting of histone tails by poly(ADP-ribose). AB - After Zn2+ finger-mediated binding to a DNA break, poly(ADP-ribose) polymerase becomes automodified with long polymers of ADP-ribose. These nucleic acid-like polymers may facilitate DNA repair by noncovalently interacting with neighboring proteins. Using a novel screening technique, we have identified histones as the predominant poly(ADP-ribose)-binding species in human keratinocytes, rat hepatocytes, frog eggs, and yeast. Polymer binding is confined specifically to the histone domains responsible for DNA condensation, i.e. histone tails. Our results indicate that polymers of ADP-ribose are targeted to sites of DNA strand breaks by poly(ADP-ribose) polymerase and subsequently function to alter chromatin conformation through noncovalent interactions with histone tails. PMID- 8349648 TI - Expression, characterization, and crystallization of oxygen-avid Ascaris hemoglobin domains. AB - The Ascaris perienteric hemoglobin is 10(4) times more oxygen-avid than mammalian hemoglobins. Inspection of its primary structure fails to explain this extraordinary association with oxygen. The Ascaris hemoglobin gene encodes a 40 kDa, two-domain globin; the two domains (D1 and D2) are 63% identical, and each is capable of binding a single heme. The native protein is an octamer. At the end of D2 is a highly charged carboxyl-terminal extension containing four direct repeats of HKEE. We have expressed the two domains separately in E. coli. Both individual domains are extremely oxygen-avid. D2, with attached COOH-terminal tail, is capable of multimerization, whereas D1 remains a monomer. Recombinant D1 readily forms diffractable, red, prismatic crystals. We conclude that: 1) the basis of the hemoglobin's oxygen avidity rests in an isolated heme pocket and does not involve inter-domain interactions and 2) multimerization is mediated through sequences in the second domain, most probably via the charged COOH terminal tail. PMID- 8349649 TI - Activation of recombinant murine cytotoxic cell proteinase-1 requires deletion of an amino-terminal dipeptide. AB - Murine cytotoxic cell proteinase-1 (granzyme B) is a member of a family of novel serine proteinases that have been implicated to participate in destruction of target cells by cytotoxic T lymphocytes. Comparison of the sequence of the cDNA with the sequence of the protein isolated from cytoplasmic granules of cytotoxic T lymphocytes suggested that this protein may be synthesized as a preproenzyme containing an amino-terminal activation dipeptide. Here we show that this activation dipeptide regulates the activity of the enzyme in hydrolysis of its preferred substrate tert-butyloxycarbonyl-Ala-Ala-Asp-thiobenzyl ester. Lysates of COS cells transfected with a vector expressing the unmodified cytotoxic cell proteinase-1 cDNA were unable to hydrolyze this substrate, whereas lysates of cells transfected with a construct in which the activation dipeptide codons has been deleted were able to hydrolyze the substrate. In each case Western blotting of the lysates revealed a form of the proteinase with an apparent molecular weight of 27,000. We conclude that the activation dipeptide regulates activity of the enzyme. This is the first report of production of an enzymatically active recombinant cytotoxic T cell serine proteinase. The strategy for successful expression of an activated form of cytotoxic cell proteinase-1 may be applicable to other members of this proteinase family. PMID- 8349650 TI - Kappa B site-dependent induction of gene expression by diverse inducers of nuclear factor kappa B requires Raf-1. AB - The transcription factor nuclear factor kappa B (NF-kappa B) is sequestered in the cytoplasm of most cell types where it is complexed with its inhibitor (I kappa B). A large variety of agents, including growth factors, the tumor promoter phorbol 12-myristate 13-acetate, and the cytokine tumor necrosis factor alpha, initiate signal transduction pathways that converge upon the NF-kappa B-I kappa B complex, resulting in the dissociation of I kappa B and the translocation of NF kappa B to the nucleus. It has been demonstrated that the phosphorylation of I kappa B is associated with NF-kappa B activation, although the kinase(s) responsible for this process in vivo remain unknown. Here we demonstrate that expression of activated forms of the GTP-binding protein Ras or of the serine/threonine kinase Raf-1 results in the activation of transcription specifically through kappa B sites. This activation appears to be dependent on NF kappa B, since co-expression of I kappa B alpha eliminates both Ras- and Raf-1 induced transcription. In addition, through the use of a dominant negative form of Raf-1, we show that Raf-1 is a common component utilized by multiple inducers in kappa B site-driven gene expression. These results illuminate a signal transduction pathway in which NF-kappa B/Rel family members participate and also implicate a pathway responsible for kappa B site-dependent gene expression during cell growth and in immune and inflammatory responses. PMID- 8349651 TI - Intramolecular electron transfer rate between active-site copper and topa quinone in pea seedling amine oxidase. AB - The equilibrium between the two substrate-reduced forms of pea seedling amine oxidase, one containing Cu(II) and reduced 3-(2,4,5-trihydroxyphenyl)-L-alanine (topa) cofactor and one containing Cu(I) and topa semi-quinone, was investigated by visible spectroscopy as a function of temperature. To determine the rate of interconversion between the two species, temperature jump relaxation studies were performed on the substrate-reduced enzyme near room temperature. The yellow radical species was found to approach its equilibrium concentration with a maximum rate constant of 43,000 +/- 3,000 s-1. This rapid equilibration is attributed to intramolecular electron transfer between copper and topa. The data indicate that the Cu(I)/topaSQ species is a kinetically competent intermediate in the reaction of amine oxidases with substrates. Furthermore, the extremely rapid electron transfer rate (kET congruent to 20,000 s-1) suggests that the topa cofactor is in close proximity to the copper atom. PMID- 8349652 TI - Phosphorylase kinase, a metal ion-dependent dual specificity kinase. AB - Phosphorylase kinase is shown to be a dual specificity kinase. The specificity of phosphorylation is determined by divalent cation. Mg2+ causes seryl phosphorylation of phosphorylase b, but Mn2+ activates tyrosine phosphorylation of angiotensin II. In contrast to seryl phosphorylation, the tyrosine kinase activity of holoenzyme is not regulated by Ca2+. Preincubation of the holoenzyme with Ca2+, Mg2+ and ATP that causes autophosphorylation activates tyrosine kinase activity. The tyrosyl kinase activity is a property of the gamma subunit. Addition of varying amounts of Mn2+ to a truncated form of the gamma subunit of phosphorylase kinase containing MgATP inhibits serine kinase but activates tyrosine kinase activity. This result along with an oxidative reaction caused by Cu2+ and site-directed mutagenesis of the putative catalytic base inhibiting both serine and tyrosine kinase activity suggest that one active site is involved in both activities. Kinetic studies with Mn2+ and ATP show that Km for nucleotide is not changed with a seryl or tyrosyl substrate. The Vm values are different, and the value for tyrosyl phosphorylation is similar to other tyrosyl kinases. We propose two conformations for the active site; one favors seryl phosphorylation, and the second tyrosyl phosphorylation is caused by the binding of divalent cation at a second metal ion binding site. PMID- 8349653 TI - Role reversal for substrates and inhibitors. Slow inactivation of D-amino acid transaminase by its normal substrates and protection by inhibitors. AB - D-Amino acid transaminase, which catalyzes the synthesis of D-alanine and D glutamate for the bacterial cell wall, is a candidate for the design of specific inhibitors that could be novel antimicrobial agents. Under the experimental conditions usually employed for enzyme assays, kinetic parameters for its substrates were determined for short incubation periods, when intermediates and products do not accumulate and the enzyme activity is linear with time. Such kinetic analyses indicate that the enzyme accepts most D-amino acids but D aspartate and D-glutamate are the best substrates. Under a different type of experimental conditions when the enzyme is exposed to D-alanine, intermediates, and products for periods of hours, it slowly becomes inactivated (Martinez del Pozo, A., Yoshimura, T., Bhatia, M. B., Futaki, S., and Manning, J. M. (1992) Biochemistry 31, 6018-6023). We now report that D-aspartate, D-glutamate, and L alanine also lead to slow inactivation. Methylation or amidation of the alpha COOH group of D-alanine prevents inactivation, indicating that decarboxylation is required for inactivation; the slow release of CO2 from substrate is demonstrated. The alpha-methyl analog of D-alanine, D-aspartate, and D-glutamate do not lead to inactivation, showing that the alpha-hydrogen of the substrate is required, i.e. that some processing is required. Lys145, which binds pyridoxal 5' phosphate in the wild-type enzyme, is not involved in the inactivation since two active site mutant enzymes, K145Q and K145N, are also inactivated. Reactivation of the inactive enzyme at acidic pH is accompanied by the release of ammonia corresponding to 1 mol/mol of dimeric enzyme. Competitive inhibitors, amine containing buffers, and thiols effectively impede the inactivation. This reversal in the roles of substrates and inhibitors, i.e. when a substrate can be an inactivator and an inhibitor can act as a protector, occurs during a time period not usually used to measure steady-state kinetics or initial velocities of enzyme reactions and could have physiological relevance in cells. PMID- 8349654 TI - Deamidation of HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system, involves asparagine 38 (HPr-1) and asparagine 12 (HPr 2) in isoaspartyl acid formation. AB - Histidine-containing protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli, when incubated at elevated temperatures forms many species of protein. The two major species are HPr-1 and HPr-2, which have been shown to lack one or two amides, respectively (Anderson, B., Weigel, N., Kundig, W., and Roseman, S. (1971) J. Biol. Chem. 246, 7023 7033). The formation of HPr-1 and HPr-2 is shown to be pH-dependent and does not occur readily below pH 6. Investigation of the identities and properties of the two residues that deamidate involved creation of site-directed mutants at the 6 glutamine and 2 asparagine residues of HPr; description of their deamidation species by isoelectric focusing; determination of their relative antibody binding properties; assay of their phosphoacceptor and phosphodonor activities; characterization of tryptic and V8-protease peptides; obtaining two-dimensional nuclear magnetic resonance spectra of HPr, HPr-1, and several mutants. It was determined that the sequential deamidation of Asn-38 and Asn-12 yields HPr-1 and HPr-2. Both residues exist as Asn-Gly pairs, and both deamidations probably form isoaspartyl acid. HPr from Bacillus subtilis and Staphylococcus carnosus which also have Asn-Gly at residues 38 and 39 form HPr-1 species presumably by deamidation. HPr from Streptococcus faecalis which does not have Asn-38 does not form a HPr-1 species. The E. coli mutant HPrs, N12D and Q51E, residues that may be involved in the active site, had impaired phosphohydrolysis properties and decreased phosphoenolpyruvate:sugar phosphotransferase system activity. PMID- 8349655 TI - Primary structure of alpha-tocopherol transfer protein from rat liver. Homology with cellular retinaldehyde-binding protein. AB - alpha-Tocopherol transfer protein (alpha TTP) present in rat liver cytosol specifically binds this vitamin and enhances its transfer between separate membranes. We previously reported purification of alpha TTP and showed that two isoforms exist in rat liver, of which the isoelectric points are 5.0 and 5.1, respectively (Sato, Y., Hagiwara, K., Arai, H., and Inoue, K. (1991) FEBS Lett. 288, 41-45). In the present paper, we have isolated a cDNA clone with 2194 base pairs encoding alpha TTP from a rat liver cDNA library. The amino acid sequence deduced from the cDNA contained all the sequences of the peptide fragments obtained by digestion of the purified protein with endoproteinase Lys-C. The isolated cDNA was found to encode the isoform with a pI of 5.0 on the basis of the cross-reactivity of the recombinant protein expressed in Escherichia coli with the isoform-specific monoclonal antibody. From the longest open reading frame of the cloned cDNA, one isoform of rat liver alpha TTP is predicted to be composed of 278 amino acid residues of calculated molecular weight 31,845. Both Western and Northern blot analyses revealed that alpha TTP is expressed exclusively in the liver in rats. alpha TTP has been found to exhibit a structural homology with the cellular retinaldehyde-binding protein present only in visual tissues. PMID- 8349656 TI - Effect of microbial and mite proteases on low and high molecular weight kininogens. Generation of kinin and inactivation of thiol protease inhibitory activity. AB - Kinin release from guinea pig plasma high molecular weight kininogen (HMWK) induced by various microbial and mite proteases has been demonstrated previously (Molla, A., Yamamoto, T., Akaike, T., Miyoshi, S., and Maeda, H. (1989) J. Biol. Chem. 264, 10589-10594; Maruo, K., Akaike, T., Matsumura, Y., Kohmoto, S., Inada, Y., Ono, T., Arao, T., and Maeda, H. (1991) Biochim. Biophys. Acta 1074, 62-68). In this paper, we describe the effects of various microbial and mite proteases on low molecular weight kininogen (LMWK) and HMWK from human plasma. A protease from the house dust mite Dermatophagoides farinae (Df-protease) directly liberated kinin from both LMWK and HMWK to a significant degree. The Km, kcat, and kcat/Km values for kinin generation from LMWK were 3.24 microM, 0.61 s-1, and 1.9 x 10(5) M-1 x s-1, respectively, and those for kinin generation from HMWK were 0.56 microM, 0.12 s-1, and 2.1 x 10(5) M-1 x s-1, respectively; kcat/Km values for Df protease were comparable with that for glandular kallikrein. In contrast, microbial proteases showed only weak kinin-releasing activity from both human plasma kininogens. Four of ten different microbial proteases liberated kinin from LMWK, and only serratial 56-kDa protease released kinin from HMWK. Furthermore, Df-protease markedly inactivated the thiol protease inhibitory activity of LMWK and HMWK, whereas all microbial proteases (as well as the endogenous protease trypsin) did not affect this inhibitory activity of both kininogens from human plasma. PMID- 8349657 TI - Age-dependent structural changes in intact human lenses detected by synchrotron radiation X-ray scattering. Correlation with Maillard reaction protein fluorescence. AB - To understand alterations in the spatial organization of the crystallins, the major determinant of lens transparency, the x-ray scattering by intact normal human lenses from individuals 6-82 years of age was measured using synchrotron radiation. The angular dependence of the integrated scattering intensity is consistent with short-range order within the crystallin assemblies. A significant change in the scattering patterns of the lenses occurs after 55 years of age, in parallel with an increase of the fluorescence of the urea-insoluble crystallin fraction. This correlation suggests a gradual derangement of the short-range order as a result of cross-linking of the crystallin subunits by advanced Maillard reaction products that are generated by the continuous reaction of sugars, such as glucose or fructose, with proteins. PMID- 8349658 TI - Tyrosine 69 of the first epidermal growth factor-like domain of human factor IX is essential for clotting activity. AB - Epidermal growth factor (EGF)-like domains are present in many extracellular proteins including clotting factor IX. Those EGF-like domains with the consensus amino acid residues Asp/Asn, Asp/Asn, Asp*/Asn*, Tyr/Phe (where * denotes a beta hydroxylated residue) bind calcium. Previous NMR studies of the isolated first EGF-like domain of human factor IX suggested that the first 3 consensus residues Asp-47, Asp-49, and Asp-64 were direct ligands for calcium. We now show from mutagenesis studies that Tyr-69 is not a direct ligand for calcium but is essential for the clotting activity of intact factor IX, specifically for the factor VIIIa-dependent activation of factor X. Surprisingly, Tyr-69 is not required for beta-hydroxylation of Asp-64. PMID- 8349659 TI - Hydrogen bonding interactions with the Schiff base of bacteriorhodopsin. Resonance Raman spectroscopy of the mutants D85N and D85A. AB - The bacteriorhodopsin (bR) mutants Asp-85-->Asn (D85N) and Asp-85-->Ala (D85A) have a red-shifted chromophore absorption and exhibit no proton pumping (Otto, H., Marti, T., Holz, M., Mogi, T., Stern, L., Engel, F., Khorana, H. G., and Heyn, M. P. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1018-1022) consistent with the hypothesis that Asp-85 functions as a counterion and proton acceptor for the retinal Schiff base (Braiman, M. S., Mogi, T., Marti, T., Stern, L. J., Khorana, H. G., and Rothschild, K. J. (1988) Biochemistry 27, 8516-8520). Resonance Raman spectroscopy reveals that these mutants contain a mixture of all-trans and 13 cis/C = N syn chromophores, similar to dark-adapted purple membrane and acid induced or deionized blue membrane. At high NaCl concentrations, both mutants adopt a predominantly all-trans chromophore structure similar to acid purple membrane. A comparison of the Schiff base C = NH+ stretch frequency (vC = N) and deuterium isotope shift for D85N, D85A as well as various forms of bR, including light-adapted bR, blue membrane, and acid purple membrane, provides information about hydrogen bonding interactions to the Schiff base. D85N has as strong a hydrogen bond as light-adapted bR despite the loss of the negative charge at residue 85. In contrast, D85A has a weaker hydrogen bond. These results can be explained if a direct interaction exists between the Schiff base and Asn-85 in D85N and between the Schiff base and a substituted water molecule in D85A. Many of the properties of wild type bR, D85N, D85A, blue membrane, and acid purple membrane can be explained on the basis of changes in the local hydrogen bonding near the Schiff base. PMID- 8349660 TI - Tumor necrosis factor-alpha (TNF-alpha) signal transduction through ceramide. Dissociation of growth inhibitory effects of TNF-alpha from activation of nuclear factor-kappa B. AB - Tumor necrosis factor-alpha (TNF-alpha) exerts pleiotropic biologic effects. Although TNF-alpha appears to activate a number of signal transduction pathways, the role of second messengers in mediating the different effects of TNF-alpha are not well defined. In this study, we investigated the role of ceramide as an intracellular mediator of TNF-alpha action. In Jurkat T cells, TNF-alpha caused early activation of the sphingomyelin cycle with peak hydrolysis of sphingomyelin observed at 30 min following addition of TNF-alpha. In this cell line, TNF-alpha caused potent activation of nuclear factor-kappa B (NF-kappa B) and exerted potent cytostatic/cytocidal activity. C2-ceramide mimicked the effects of TNF alpha on cell growth in a dose-dependent manner, but C2-ceramide was unable to induce activation of NF-kappa B under multiple conditions investigated. C2 ceramide, however, enhanced activation of NF-kappa B in response to TNF-alpha with peak effects observed at a concentration of C2-ceramide of 5 microM. Thus, ceramide functions as a selective mediator of the cytostatic/cytotoxic effects of TNF-alpha and plays a positive feedback role in activation of NF-kappa B. TNF alpha signaling, therefore, involves multiple second-messenger pathways that function independently or coordinately to transduce distinct functions of TNF alpha. PMID- 8349661 TI - Characterization, cloning, and in vitro expression of the extremely thermostable glutamate dehydrogenase from the hyperthermophilic Archaeon, ES4. AB - Glutamate dehydrogenase (GDH) from the hyperthermophilic Archaeon ES4 (optimal growth temperature 98 degrees C and maximum growth temperature 110 degrees C) was purified to homogeneity. The purified native enzyme had an M(r) of 270,000 +/- 5,000 and was shown by gel filtration and SDS-polyacrylamide gel electrophoresis to be a hexamer with identical subunits of M(r) = 46,000 +/- 3,000. The hexameric subunit composition was also evident from electron micrographs, which show a triangular antiprism structure very similar to that of bovine GDH. The enzyme is exceptionally thermostable, with a half-time of inactivation of 3.5 h at 105 degrees C. Differential scanning calorimetry revealed a tm for denaturation of 113 degrees C, and a tm for activation at 60 degrees C. Antigenic cross-reaction with ES4 GDH was observed with the purified GDH from the thermophilic Archaea, Pyrococcus furiosus and Thermococcus litoralis as well as with bovine and yeast GDHs. The genome of ES4 was shown to contain a single copy of the gdhA gene, and this was cloned and sequenced. The deduced amino acid sequence of the GDH from ES4 corresponded to the NH2-terminal amino acid sequence obtained from the pure protein. From the nucleotide sequence the ES4 protein is composed of 420 residues. It has a relatively high hydrophobicity and a low number of sulfur containing residues compared with mesophilic GDHs. Relatively high homology (52%) exists between the deduced amino acid sequence of ES4 GDH and Clostridium difficile GDH. Of the two distinct families of GDH sequences known, ES4 GDH belongs to the same family as vertebrates, C. difficile, and other Archaea. The gdhA gene of ES4 was expressed in vitro in a rabbit reticulocyte cell-free lysate, thus providing a system for structural studies of the mechanisms of thermostability in hyper-thermophilic proteins. PMID- 8349662 TI - Isotope effects and alternative substrate reactivities for tryptophan 2,3 dioxygenase. AB - Tryptophan 2,3-dioxygenase (EC 1.13.1.12) is a hemoprotein which catalyzes the first step in the oxidative degradation of tryptophan. The reaction is believed to proceed by addition of O2 across the 2,3-bond of the indole ring, followed by decomposition of the resultant dioxetane to give N-formylkynurenine. A primary D2O isotope effect of 4.4 on Vmax/Km was observed at the pH optimum, pH 7.0. This implies that abstraction of the indole proton is at least partially rate determining. An inverse secondary isotope effect of 0.96 was observed for L-[2 3H]tryptophan at this pH. The secondary isotope effect signals the formation of the C-O bond at C-2. As the rate of proton abstraction increased with increasing pH, the D2O isotope effect decreased to 1.2 at pH 8.5 and the secondary isotope effect increased to 0.92. The rate-determining steps therefore change with increasing pH, and bond formation at C-2 becomes more rate-limiting. The secondary isotope effect did not change significantly with varying O2 concentration so that substrate binding is primarily ordered with O2 binding first. The specificity of the enzyme towards substituted tryptophans shows that substitution of the phenyl ring of the indole is sterically unfavorable. Steric hindrance is highest at the 4- and 7-positions, while the 5- and 6-positions are less sensitive. 6-Fluoro-L-tryptophan was more reactive than tryptophan, and the increased reactivity can be explained by an electronic effect that enhances of the rate of C-O bond formation at C-2. PMID- 8349663 TI - Characterization of the effects of a thymine glycol residue on the structure, dynamics, and stability of duplex DNA by NMR. AB - A duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6 dihydrothymidine) has been studied by NMR and other methods. Oxidative stress, ionizing radiation, and other causes can induce the oxidation of thymine to thymine glycol. The presence of thymine glycol is known to have significant biological consequences, and there are repair enzymes for thymine glycol in a wide range of organisms. These studies have been carried out on the DNA duplex of d(C1G2C3A4G5Tg6C7A8G9C10C11) paired with d(G22C21G20T19C18A17G16T15C14G13G12), with Tg indicating thymine glycol. The presence of thymine glycol lowers the thermal stability of duplex DNA. The NMR results indicate that thymine glycol induces a large, localized structural change in duplex DNA with the thymine glycol base being extrahelical as well as the opposing base on the complementary strand. This structural information is consistent with the biological consequences of thymine glycol in DNA. PMID- 8349664 TI - Partial purification and characterization of a (glycosyl) inositol phospholipid specific phospholipase C from peanut. AB - We have isolated a glycosyl inositol phospholipid (GIP) anchor-hydrolyzing activity from peanut seeds by a series of column chromatographic steps. The activity has a pH optimum below 6.0, requires calcium, and is inhibited by sulfhydryl reagents. It cleaves the GIP anchors of solubilized acetylcholinesterase from bovine erythrocytes and variant surface glycoprotein from Trypanosoma brucei. On the other hand, it does not act on membrane-bound GIP anchored substrate or on inositol-acylated GIP anchor of human erythrocyte acetylcholinesterase. The only product released from [3H]myristate-labeled variant surface glycoprotein following treatment with the activity from peanut was 3H-labeled diacylglycerol. Together, these findings identify the activity from peanut seeds as a GIP anchor-hydrolyzing phospholipase C. The enzyme has been found to hydrolyze not only protein GIP anchors but also phosphatidylinositol, whereas it shows no activity against other phospholipids. The water-soluble products of phosphatidylinositol hydrolysis by peanut phospholipase C were characterized as a mixture of inositol 1,2-cyclic phosphate and inositol phosphate. PMID- 8349665 TI - Vaccinia virus ribonucleotide reductase expression and isolation of the recombinant large subunit. AB - The vaccinia virus gene encoding the 87-kDa protein that comprises the large subunit of ribonucleotide reductase (vvR1) was cloned into a bacterial expression vector under the control of an inducible promoter. Culture of Escherichia coli cells harboring the recombinant plasmid under standard induction conditions (0.4 mM isopropyl beta-D-thiogalactopyranoside, 37 degrees C) resulted in synthesis of a completely insoluble product. Production of soluble vvR1 was achieved by growing bacteria at low temperature (15 degrees C) during the induction period, initiating induction at low cell density, and using a low concentration (0.05 mM) of the inducer isopropyl beta-D-thiogalactopyranoside. Hydroxyurea, an inhibitor of ribonucleotide reductase, increased production of soluble vvR1 in a dose dependent manner. Recombinant vvR1 was purified from a high salt extract of the E. coli lysate in four steps, the last utilizing an affinity column consisting of the carboxyl-terminal seven amino acids of the vvR2 protein linked to an insoluble resin. Using purified recombinant vvR2 to reconstitute active enzyme, we determined that maximizing the rate of CDP reduction required pH 8.0-8.8, 50 mM dithiothreitol, and 2 mM ATP. Specific activity of purified vvR1 was 122 nmol/min/mg. Limited proteolysis of the vvR1 protein revealed protease-resistant fragments approximately 30 and 58 kDa in size. To our knowledge, this study represents the first expression, solubilization, and isolation of a recombinant "eukaryotic" form of ribonucleotide reductase large subunit. PMID- 8349666 TI - Use of bismannose photolabel to elucidate insulin-regulated GLUT4 subcellular trafficking kinetics in rat adipose cells. Evidence that exocytosis is a critical site of hormone action. AB - The subcellular trafficking of tracer-tagged GLUT4 between the plasma membranes and low-density microsomes of rat adipose cells has been studied. Cell-surface GLUT4 have been initially tracer-tagged in the insulin-stimulated state with the [3H]bismanose photolabel 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D mannos- 4-yloxy)-2- propylamine. The half-time for internalization of tracer tagged GLUT4 when insulin is removed by collagenase treatment is similar to that observed for the decrease in immunodetectable GLUT4 in the plasma membranes and the decrease in glucose transport activity in the intact cells. In contrast, internalization of tracer-tagged GLUT4 also occurs when cells are maintained in the continuous presence of insulin even though the plasma membrane level of immunodetectable GLUT4 and glucose transport activity in the intact cells are unaltered. These data show, for the first time, that insulin has little, if any, effect on the rate constant for GLUT4 endocytosis, but instead, primarily increases the rate constant for exocytosis. Tracer-tagged GLUT4 that is returned to the low-density microsomes can be restimulated with fresh insulin to recycle to the plasma membranes and to a steady-state distribution level that is the same as that observed in cells that are maintained in the continuous presence of insulin. These data suggest that the cells' entire complement of GLUT4 is involved in the recycling process. Following insulin stimulation of adipose cells initially in the basal state, the increase in immunodetectable GLUT4 in the plasma membranes precedes the increase in accessibility of GLUT4 to exofacial 2-N 4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2- propylamine photolabeling, and this in turn precedes the increase in cellular glucose transport activity. Such time course data suggest that there may be plasma membrane intermediate states in the GLUT4 trafficking pathway. The kinetic properties of GLUT4 translocation and its recycling have been interpreted in terms of a subcellular trafficking model that identifies exocytosis, possibly involving-hypothetical "docking" and "fusion" steps, as the critical site of hormone action. PMID- 8349667 TI - Cloning and site-directed mutagenesis of human ADP-ribosylarginine hydrolase. AB - Mono-ADP-ribosylation of arginine is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the opposing reactions in the cycle. ADP-ribosylarginine hydrolases differ in their dithiothreitol (DTT) requirements. Rat and mouse hydrolases require DTT for maximal activity, but calf, guinea pig, and human hydrolases are DTT-independent. To define the molecular basis for these differences, brain ADP ribosylarginine hydrolases were cloned. Deduced amino acid sequences of mouse and rat hydrolases were 94% identical with 5 conserved cysteines. The human hydrolase sequence was 83% identical to that of rat but contained only 4 cysteines with cysteine 108 in rat corresponding to serine 103 in human. To investigate the role of rat cysteine 108, human and rat wild-type hydrolases and mutants, in which serine 103 in human was replaced by cysteine (S103C) and cysteine 108 in rat was replaced by serine (C108S), were expressed in Escherichia coli. Affinity-purified anti-rat brain hydrolase antibodies reacted with recombinant wild-type rat hydrolase, but only weakly with the C108S mutant. They did not react with human wild-type or the S103C mutant. Human hydrolase and rat C108S were DTT independent; human S103C was, however, DTT-dependent. These data clearly show that cysteine 108 in rat hydrolase plays a critical role in DTT dependence and may be important in immunoreactivity. PMID- 8349668 TI - Steady state kinetics of mannitol phosphorylation catalyzed by enzyme IImtl of the Escherichia coli phosphoenolpyruvate-dependent phosphotransferase system. AB - The kinetics of mannitol phosphorylation catalyzed by enzyme IImtl of the bacterial P-enolpyruvate-dependent phosphotransferase system are described for three different physical conditions of the enzyme, (i) embedded in the membrane of inside-out (ISO) oriented vesicles, (ii) solubilized and assayed above the critical micellular concentration (cmc) of the detergent, and (iii) solubilized and assayed below the cmc of the detergent. The kinetic characteristics of enzyme IImtl, after solubilization of cytoplasmic membranes or after purification from these membranes are comparable. The mannitol-dependent kinetics at saturating concentration of P-HPr were biphasic both for the solubilized enzyme assayed above the cmc and for the enzyme in ISO vesicles. In contrast, the mannitol dependent kinetics was monophasic for the solubilized enzyme assayed below the cmc. In the latter case, the maximal rate was about twice as high as observed with the two other conditions. The contribution of the high affinity phase to the maximal rate is lower for enzyme IImtl in ISO vesicles than for the solubilized enzyme. At limiting concentrations of P-HPr, the kinetics is not according to the expected "ping-pong" mechanism. PMID- 8349669 TI - A method to study complex enzyme kinetics involving numerical analysis of enzymatic schemes. The mannitol permease of Escherichia coli as an example. AB - An analysis of complex kinetic mechanisms is proposed that consists of two steps, (i) building of an kinetic scheme from experimental data other than steady-state kinetics and (ii) numerical simulation and analysis of the kinetics of the proposed scheme in relation to the experimental kinetics. Procedures are introduced to deal with large numbers of enzymatic states and rate constants, and numerical tools are defined to support the analysis of the scheme. The approach is explored by taking the mannitol permease of Escherichia coli as an example. This enzyme catalyzes both the transport of mannitol across the cytoplasmic membrane and the phosphorylation of mannitol. The challenge is to deduce the transport properties of this dimeric enzyme from the phosphorylation kinetics. It is concluded that (i) the steady-state kinetic behavior is largely consistent with the proposed catalytic cycle of the monomeric subunit, (ii) the kinetics provide no direct support but also do not disprove a coupled translocation of the binding sites on the two monomeric subunits. The approach reveals the need for further experimentation where the implementation of experimental results in the scheme conflict with the experimental kinetics and where specific experimental characteristics do not show up in the simulations of the proposed kinetic scheme. PMID- 8349670 TI - Role of the COOH-terminal acidic region of A1 subunit in A2 subunit retention in human factor VIIIa. AB - Factor VIIIa is a heterotrimer of A1,A2 and A3-C1-C2 subunits which is labile due to a relatively weak affinity interaction between the A2 subunit and the Me(2+) linked A1/A3-C1-C2 dimer. Previously we speculated that the acidic region at the COOH terminus of the A1 subunit was involved with the A2 subunit retention. This region, delineated by factor VIII residues 337-372, was chemically synthesized. Both the peptide, designated FVIII337-372, and an IgG fraction prepared from rabbit anti-FVIII337-372 antiserum inhibited the reconstitution of factor VIIIa from A1/A3-C1-C2 dimer plus A2 subunit. A primary component of the inhibitory activity of the peptide was attributed to its acidic nature based upon similar inhibition of factor VIIIa reconstitution using a synthetic polymer of aspartic acid. Trypsin cleaved the peptide at Arg359 and the resultant two fragments were isolated. Inhibitory activity was associated with the NH2-terminal fragment which contained 10 of the 13 acidic residues present in the original peptide. The fluorescence of a dansylated FVIII337-372 was enhanced 2-fold by A2 subunit and this effect was reversed by addition of excess unmodified peptide. The inhibitory activity of FVIII337-372 was attenuated by the presence of Ca2+. Ca2+ also inhibited the reconstitution of factor VIIIa in the absence of peptide and increased the rate and extent of factor VIIIa decay, suggesting that Ca2+ effectively shielded charges important for the intersubunit interactions. The above results support a role for this acidic region in the association of A2 subunit with A1/A3-C1-C2 dimer. PMID- 8349671 TI - Analysis of microsomal cholesteryl ester hydrolases by radiation inactivation. AB - Radiation inactivation by high energy electrons, a method for determining the size of a protein without prior purification, was used to study the acid and neutral cholesteryl ester hydrolase (CEH) activities of rat liver microsomes. The same preparations were also assayed for the microsomal, "nonspecific" carboxylesterases using o-nitrophenyl acetate as substrate. Non-specific esterase activity surviving radiation could be fit to a single exponential function, the slope of which yielded a target size of 47 +/- 5 kDa (mean +/- S.D., n = 7). Surviving CEH activity assayed at pH 5 could also be fit to a single exponential that yielded a target size of 71 +/- 14 kDa (n = 5). In contrast, the surviving CEH activity assayed at pH 7 was more complex. The data from six experiments were described as the sum of two exponentials, indicating that most of the activity is due to an entity that is three to four times larger and a minor amount to one that is half the size of the pH 5 enzyme. The results are consistent with the suggestion that the acid and neutral microsomal CEH activities are due to distinct enzymes, which are not the "nonspecific" carboxylesterases. Their sizes also differ from those previously determined for lysosomal acid lipase and other lipases in the liver. PMID- 8349672 TI - Nitric oxide-independent, thiol-associated ADP-ribosylation inactivates aldehyde dehydrogenase. AB - Nitric oxide inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase and stimulates NAD-dependent automodification of a cysteine (Dimmeler, S., Lottspeich, F., and Brune, B. (1992) J. Biol. Chem. 267, 16771-16774). Another NAD-utilizing dehydrogenase that has a catalytic cysteine, aldehyde dehydrogenase (ALDH), was also inhibited by nitric oxide. Unlike glyceraldehyde-3-phosphate dehydrogenase, ALDH was modified in a nitric oxide-independent process by ADP ribose, but not by NAD. Modification, which proceeded to > 2 mol ADP-ribose.mol ALDH-1, was associated with an exponential decrease in enzyme activity to less than 10% of control. Two types of evidence suggested modification of the ALDH active site: 1) ADP-ribose inhibited ALDH competitively (Ki = 0.46 mM) with respect to NAD (Km = 0.11 mM) in brief incubations and 2) the presence of substrates protected ALDH from both modification and inhibition by ADP-ribose. The ALDH-ADP-ribose bond was sensitive to base and mercuric ion and stable to acid and neutral hydroxylamine, properties shared with the ADP-ribosylcysteine linkage synthesized enzymatically by pertussis toxin. These data demonstrate a novel means of inactivation of an NAD-dependent enzyme, namely the affinity-based modification of the enzyme NAD site by ADP-ribose, and suggest that nonenzymatic ADP-ribosylation may be responsible for modification of cysteine residues. PMID- 8349673 TI - Isolation of an autoinhibitory region from the regulatory beta-subunit of phosphorylase kinase. AB - An equimolar mixture of the regulatory alpha- and beta-subunits of phosphorylase kinase has been shown to inhibit its catalytic gamma-subunit (Paudel, H.K., and Carlson, G.M. (1987) J. Biol. Chem. 262, 11912-11915). The possible presence of an autoinhibitory sequence within those regulatory subunits has been evaluated by peptide isolation and characterization following chemical and proteolytic cleavage of an isolated equimolar mixture of those subunits; the peptides generated were tested for their ability to inhibit the activity of a complex of the gamma-subunit and calmodulin. An isolated inhibitory fragment, hereafter referred to as I-peptide, was sequenced and found to correspond to residues 420 436 of the beta-subunit (KRNPGSQKRFPSNCGRD). This sequence showed homology with the kinase's natural substrate, phosphorylase b. A synthetic peptide based on this sequence was constructed and used to study the mechanism of inhibition. Kinetic analysis of the inhibition of the gamma-subunit-calmodulin complex by the I-peptide revealed a competitive pattern versus the homologous substrate phosphorylase b and an uncompetitive pattern versus MgATP, suggesting an ordered binding of substrates, with the nucleotide binding first. In addition to its ability to inhibit, the I-peptide was also a substrate for the gamma-subunit calmodulin complex, with a relatively good Km but poor Vmax. The parallel inhibition of free gamma-subunit and the gamma-subunit-calmodulin complex by progressively increasing concentrations of I-peptide provided further evidence that the peptide inhibits by interacting directly with the catalytic subunit and not with the stimulatory calmodulin molecule. The results of this study are consistent with previous findings from this laboratory showing that the conformation of the beta-subunit changes following activation of phosphorylase kinase through a variety of mechanisms. PMID- 8349674 TI - The presence of UDP-N-acetylglucosamine:alpha-3-D-mannoside beta 1,2-N acetylglucosaminyltransferase I activity in Spodoptera frugiperda cells (IPLB-SF 21AE) and its enhancement as a result of baculovirus infection. AB - A Golgi preparation from Spodoptera frugiperda (IPLB-SF-21AE) cells was incubated in the presence of the mannosidase II inhibitor, swainsonine, with the oligosaccharide, M(alpha 1,3)[[M(alpha 1,3)[M(alpha 1,6)]M(alpha 1,6)]] M(beta 1,4)Gn(beta 1,4)Gn (M5Gn2), the preferred substrate for the enzyme, UDP-N acetylglucosamine:alpha-3-D-mannoside beta 1,2-N-acetylglucosaminyltransferase I (Gn-TI). This resulted in formation of the product, Gn(beta 1,2)M(alpha 1,3)[[M(alpha 1,3)[M(alpha 1,6)]M(alpha 1,6)]]- M(beta 1,4) Gn(beta 1,4)Gn (Gn(I)M5Gn2). A significantly increased (> 4-fold) rate of conversion of M5Gn2 to Gn(I)M5Gn2 occurred with insect cell-derived Golgi preparations that had been infected with a recombinant baculovirus for 66 h, a time at which significant amounts of complex-type oligosaccharides were assembled on a heterologous protein, human plasminogen, expressed in this system. Coupled with previous results (Davidson, D.J., Bretthauer, R.K., and Castellino, F.J. (1991) Biochemistry 30, 9811-9815) that demonstrated the occurrence of virally induced activation of a specific M6-mannosidase in IPLB-SF-21AE cells, it is clear that viral infection of lepidopteran insect cells makes available enzymes that provide and utilize the substrate, M5Gn2-protein. This is a key feature in the explanation of the previous original observations made by this laboratory, that lepidopteran insect cells are capable of assembly of complex-type oligosaccharides on glycoproteins. PMID- 8349675 TI - Molecular dynamics simulation of NO recombination to myoglobin mutants. AB - Molecular dynamics simulations on two coupled electronic surfaces are employed to investigate the geminate recombination of nitric oxide to mutants of sperm whale myoglobin. A model for the ground and the excited states is constructed based on experimental data. The crossing between the surfaces is treated using the Landau Zener formula. The reaction probability and the recombination curves are calculated directly by histogramming the results of an ensemble of trajectories. The experimental trend is reproduced in which the picosecond recombination rate of different mutants increases in the order Phe29 > Leu29 > Val29 > Ala29. Furthermore, in accord with the experiment on significantly longer time scales an opposite trend is obtained, in which the recombination rate for Ala29 is larger than for Phe29. These results are explained by constrained diffusion of the ligand in the heme pocket. The average and the transient volume of the heme pocket is modified by the 29 mutants. PMID- 8349676 TI - Overexpression of human lipoprotein lipase in transgenic mice. Resistance to diet induced hypertriglyceridemia and hypercholesterolemia. AB - Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. To determine the role of LPL in lipoprotein metabolism, we established three transgenic mouse lines overexpressing the human LPL gene; the highest expressor line, which transcribed human LPL mRNA in the heart, skeletal muscles, and adipose tissue, was used in this study. The transgenic mice had 5- and 1.7-fold higher LPL activity in adipose tissue and post-heparin plasma, respectively. Plasma triglyceride levels in transgenic mice were 24.2% of that in control mice, and gel filtration chromatography showed that very low density lipoprotein (VLDL) triglycerides were much reduced in transgenic mice. In the chemical analysis of plasma lipoproteins isolated by ultracentrifugation, we found that LDL particles were cholesterol-rich and HDL2 cholesterol was increased 1.4-fold in transgenic mice as compared to control mice. When we injected 125I VLDL intravenously into transgenic mice, the clearance of 125I-VLDL and the conversion of VLDL to LDL was markedly enhanced as compared to control mice. Furthermore, the clearance of chylomicrons, estimated by both the fat loading and retinyl palmitate loading tests, was significantly enhanced in transgenic mice. After sucrose feeding, no increase in VLDL was observed in transgenic mice. When fed a high cholesterol diet, the development of hypercholesterolemia was suppressed in transgenic mice. These results suggested that LPL determined not only hydrolysis of triglyceride-rich lipoproteins but also lipolytic conversion, and that overexpression of LPL acted to protect against diet-induced hypertriglyceridemia as well as hypercholesterolemia. PMID- 8349677 TI - Interactions between pyruvate carboxylase and other mitochondrial enzymes. AB - Although pyruvate carboxylase associated with both mitochondrial aspartate aminotransferase and malate dehydrogenase, it had a higher affinity for the amino transferase. Furthermore, the aminotransferase enhanced dissociation of malate dehydrogenase from pyruvate carboxylase. Glutamate dehydrogenase did not associate with pyruvate carboxylase alone, but it apparently associated with the pyruvate carboxylase-aminotransferase complex, and malate dehydrogenase associated with the resulting ternary complex. Citrate synthase and other proteins tested did not associate with pyruvate carboxylase. However, citrate synthase associated with the pyruvate carboxylase-malate dehydrogenase complex. Apparently as a consequence of these heteroenzyme interactions, the rate of the pyruvate carboxylase reaction was slightly greater when coupled with malate dehydrogenase or both malate dehydrogenase and citrate synthase than when coupled with citrate synthase alone. In addition, in the presence of both coupling enzymes, the rate of conversion of pyruvate to citrate was higher than predicted on the basis of the Michaelis-Menten relationship of the two coupling enzymes. Therefore, binding of malate dehydrogenase to pyruvate carboxylase enhances pyruvate carboxylase activity. Association of citrate synthase with the malate dehydrogenase-pyruvate carboxylase binary complex does not alter activation of pyruvate carboxylase but results in citrate synthase being more reactive than free citrate synthase with oxalacetate. PMID- 8349678 TI - Identification of the region on the class I histocompatibility molecule that interacts with the molecular chaperone, p88 (calnexin, IP90). AB - During early stages in their biogenesis, murine class I histocompatibility molecules interact transiently with a molecular chaperone of the endoplasmic reticulum designated p88. Using a series of mutant class I heavy chains we mapped the region of the heavy chain that interacts with p88. Domain deletion mutants of the H-2Db and H-2Kb molecules revealed that most of the extracellular portion of the heavy chain and the bulk of the cytoplasmic domain were not required for the association. However, replacement of the transmembrane segment and cytoplasmic domain with a glycosyl phosphatidylinositol anchor from Q7b resulted in a heavy chain that was incapable of interaction with p88. These results suggested that the primary site of interaction with p88 is within a region containing the transmembrane segment and several flanking amino acids of the class I heavy chain. This finding was supported by replacing the glycosyl phosphatidylinositol anchor of the noninteracting Q7b protein with segments of the Db heavy chain containing the putative interaction site and showing that the hybrids were capable of associating with p88. The apparent lack of interaction between segments of p88 and the class I heavy chain that are present within the lumen of the endoplasmic reticulum was also observed when the association between p88 and the alpha chain of the T cell receptor was examined. The full-length transmembrane alpha chain formed a complex with p88, whereas a soluble variant consisting of most of the luminal portion of the alpha chain exhibited only minimal interaction. Thus, p88 is capable of associating with nascent integral membrane proteins through transmembrane interactions that are unavailable to the major soluble chaperone of the endoplasmic reticulum, BiP (GRP78). PMID- 8349679 TI - Activity of both Raf and Ras is necessary for activation of transcription of the human T cell receptor beta gene by protein kinase C, Ras plays multiple roles. AB - Transcription of the T cell receptor beta gene is up-regulated during T cell activation. We have previously defined the elements within the TcR beta gene enhancer responsible for increased transcription in response to phorbol esters, which mimic part of the pathway for T cell activation. Using a reporter construct (beta E2 x 4) containing four copies of this inducible element, activation was achieved by the addition of phytohemagglutinin or phorbol esters. Activation was observed after 2 h of treatment, was maximal by 8 h, and could be blocked by the protein synthesis inhibitor cycloheximide. Coexpression of v-Ha-Ras-, v-Raf-, and v-Src-activated beta E2 x 4, and constitutively active mutants of protein kinase C also increased transcription from this construct. Calcium ionophore generated signals which synergized with both Ras and protein kinase C. Expression of a truncated Raf protein which has been shown to act in a dominant negative manner, was able to inhibit activation of beta E2 x 4, demonstrating that Raf plays an important role in T cell signaling. A dominant negative mutant of v-Ha-Ras inhibited all methods of activation tested, including transfection with v-Raf. Thus, Ras activity appears to be necessary at more than one point in the transduction of signals from T cell receptor to nucleus. PMID- 8349680 TI - The propeptide is required for in vivo formation of stable active yeast proteinase A and can function even when not covalently linked to the mature region. AB - The PEP4-encoded aspartate protease proteinase A from Saccharomyces cerevisiae is synthesized as a zymogen (Ammerer, G., Hunter, C. P., Rothman, J. H., Saari, G. C., Valls, L. A., and Stevens, T. H. (1986) Mol. Cell. Biol. 6, 2490-2499; Woolford, C. A., Daniels, L. B., Park, F. J., Jones, E. W., van Arsdell, J. N., and Innis, M. A. (1986) Mol. Cell. Biol. 6, 2500-2510). We constructed a mutant form, lacking the propeptide. This form, still containing the signal peptide, was translocated into the endoplasmic reticulum, but the mature region was subsequently completely degraded. When a plasmid encoding only the propeptide after the signal peptide was introduced into a strain producing the mature region, a subpopulation of mature region molecules was rescued from the degradation and gained activity. Increased activity was found when the mature region was co-produced with increased amounts of propeptide, whereas truncated propeptides, lacking residues at its C terminus, were less efficient in the interaction with the mature region. We propose that the mature region of proteinase A cannot fold into its stable active conformation in the absence of the propeptide and that the propeptide can promote folding of the mature region, even when the propeptide and the mature region are not covalently linked. PMID- 8349681 TI - Characterization of the molecularly cloned murine alpha-globin transcription factor CP2. AB - We recently cloned human and murine cDNAs that encode CP2, a transcription factor that interacts with the murine alpha-globin promoter. In this report, we exploited our ability to express CP2 in bacteria and eukaryotic cells to further investigate factor activities in vitro and in vivo. CP2 expressed in bacteria was significantly enriched and used in a series of DNase I footprinting and electrophoretic gel shift assays. The results suggest that CP2 binds a hyphenated recognition sequence motif that spans one DNA helix turn. In addition, the enriched bacterial protein activated transcription of alpha-globin promoter templates approximately 3- to 4-fold in vitro. We then tested the effect of elevating CP2 levels 2.5- to 5.5-fold in vivo using both transient and stable transformation assays. When a reporter construct comprised of the intact murine alpha-globin promoter driving the bacterial chloramphenicol acetyltransferase (CAT) gene was introduced into these overexpressing cells, we observed a 3- to 6 fold increase in CAT activity when compared to cells expressing normal levels of CP2. These results define the CP2 factor binding site in more detail and help characterize the activities of the factor in vivo. PMID- 8349682 TI - Histidine 296 is essential for the catalysis in Lactobacillus plantarum D-lactate dehydrogenase. AB - Two His residues, His-205 and His-296, in Lactobacillus plantarum D-lactate dehydrogenase are highly conserved in the D-isomer-specific 2-hydroxyacid dehydrogenase family, suggesting that they are candidates for the catalytic His in the enzyme. The substitution of His-296 with Tyr by means of site-directed mutagenesis induced a drastic decrease in the reaction rate, while a His-205 to Tyr substitution induced no large change in the catalytic properties. In pyruvate reduction, the Tyr-296 enzyme showed a slightly increased Km below pH 6.0 but no significant pH dependence above pH 6.0, where the wild-type enzyme showed an increased Km value. In D-lactate oxidation, in contrast, the Tyr-296 enzyme showed a greatly increased Km value for D-lactate and strong pH dependence. An additional substitution of His-296 with Gln induced more complete loss of the catalytic activity. In contrast to the Tyr-296 enzyme, the Gln-296 enzyme showed a greatly increased Km value and a strong pH-dependent reaction rate even in pyruvate reduction. Unlike the wild-type or His-205 enzyme, both the Tyr-296 and Gln-296 enzymes showed significant resistance against diethyl pyrocarbonate. These results clearly indicate that His-296 is essential for the catalysis by D lactate dehydrogenase, as in the case of His-195 in L-lactate dehydrogenase. PMID- 8349684 TI - Purification and characterization of active human interleukin-1 beta-converting enzyme from THP.1 monocytic cells. AB - Interleukin-1 beta-converting enzyme (ICE) was purified from dialyzed cytoplasmic extracts of THP.1 human monocytic cells by a combination of DEAE-5PW and SP-5PW ion exchange and C4 reverse phase high performance liquid chromatography. Sequence information from tryptic and Asp.N peptides on the isolated 20-kDa (p20) and a 10-kDa (p10) proteins enabled the subsequent cloning of ICE (Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., Kostura, M. J., Miller, D. K., Molineaux, S. M., Weidner, J. R., Aunins, J., Elliston, K. O., Ayala, J. M., Casano, F. J., Chin, J., Ding, G. J.-F., Egger, L. A., Gaffney, E. P., Limjuco, G., Palyha, O. C., Raju, S. M., Rolando, A. M., Salley, J. P., Yamin, T.-T., Lee, T. D., Shively, J. E., MacCross, M., Mumford, R. A., Schmidt, J. A., and Tocci, M. J. (1992) Nature 356, 768-774) and localized the active site Cys. Immunoblots with ICE specific antibodies and NH2-terminal sequencing indicated that ICE active column fractions contained in addition to p20 and p10 an alternatively processed form of the p20 protein (p22) containing an extra 16 amino acids NH2-terminal to the p20. Furthermore, immunoblot analysis of the ion exchange column effluent showed that p20 and p22 were found together in three separate fractions distinguished by differences in p10: an intact p10 with complete ICE activity, a COOH-terminally truncated form of p10 with decreased ICE activity, and an absence of p10 with no ICE activity. These results indicate that the p10 protein is essential for ICE activity and that the ICE holoenzyme contains an intact p10 subunit paired with a p20 or p22 catalytic subunit. PMID- 8349683 TI - Intestinal bile acid absorption. Na(+)-dependent bile acid transport activity in rabbit small intestine correlates with the coexpression of an integral 93-kDa and a peripheral 14-kDa bile acid-binding membrane protein along the duodenum-ileum axis. AB - The anatomical localization of the Na+/bile acid cotransport system from rabbit small intestine was determined using brush border membrane vesicles prepared from eight different segments of the small intestine. Na(+)-dependent transport activity for bile acids, both for [3H]taurocholate and [3H]cholate, was found in the distal segment 8 only representing the terminal 12% of the small intestine. In contrast, the Na(+)-dependent D-glucose transporter and the H(+)-dependent oligopeptide transporter were found over the whole length of rabbit small intestine in all segments. Photoaffinity labeling with 7,7-azo- and 3,3-azo derivatives of taurocholate with subsequent fluorographic detection of labeled polypeptides after one- and two-dimensional gel electrophoresis showed that an integral membrane polypeptide of M(r) 87,000 is present in the entire small intestine, whereas an integral membrane protein of M(r) 93,000 together with a peripheral membrane protein of M(r) 14,000 are exclusively expressed in the distal small intestine correlating with Na(+)-dependent bile acid transport activity. Photoaffinity labeling with the cationic bile acid derivative 1-(7,7 azo-3 alpha,12 alpha-dihydroxy-5 beta[3 beta-3H]cholan-24-oyl)-1,2- diaminoethane hydrochloride and 7,7-azo-3 alpha,12 beta-dihydroxy-5 beta[12 alpha-3H]cholan-24 oic acid did not result in a specific labeling of the above mentioned proteins, demonstrating their specificity for physiological bile acids. Photoaffinity labeling of the 93- and 14-kDa bile acid-binding proteins was strongly Na(+) dependent. Significant labeling of the 93- and 14-kDa proteins occurred only in the presence of Na+ ions with maximal labeling above 100 mM [Na+] showing a parallel [Na+] dependence to transport activity. Inactivation of Na(+)-dependent [3H]taurocholate uptake by treatment of ileal brush border membrane vesicles with 4-nitrobenzo-2-oxa-1,3-diazol chloride led to a parallel decrease in the extent of photoaffinity labeling of both the 93- and 14-kDa protein. Sequence analysis of the membrane-bound 14-kDa bile acid-binding protein surprisingly revealed its identity with gastrotropin, a hydrophobic ligand-binding protein exclusively found in the cytosol from ileocytes and thought to be involved in the intracellular transport of bile acids from the brush border membrane to the basolateral pole of the ileocyte. In conclusion, the present studies suggest that both an integral 93- and a peripheral 14-kDa membrane protein, identified as gastrotropin, and both exclusively expressed in the terminal ileum, are essential components of the Na+/bile acid cotransport system in rabbit terminal ileum. PMID- 8349685 TI - The sequence-specific high mobility group 1 box of TCF-1 adopts a predominantly alpha-helical conformation in solution. AB - The High Mobility Group (HMG) 1 box is a protein motif that mediates DNA binding in a novel family of transcription-regulating proteins. Several members of this family, including the lymphoid-specific proteins TCF-1 and LEF-1 and the mammalian sex-determining factor SRY, carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof. To initiate studies on the structural characteristics of the TCF-1 HMG box, we have expressed the 87-amino acid HMG box in milligram quantities in Escherichia coli and purified the soluble peptide to > 95% homogeneity. The peptide bound DNA with the same specificity as the complete protein and was capable of inducing DNA bending. Circular dichroism (CD) analysis revealed the TCF-1 HMG box to adopt an approximately 60% alpha-helix/40% random coil conformation in solution. In the presence of an equimolar amount of double-stranded DNA containing the cognate motif, the CD spectrum changed significantly, implying the induction of a structural modification upon DNA/protein association. PMID- 8349686 TI - A hinge region mutation in C1-inhibitor (Ala436-->Thr) results in nonsubstrate like behavior and in polymerization of the molecule. AB - C1-inhibitor(Mo), a dysfunctional C1-inhibitor molecule produced in two kindred with type II hereditary angioedema, has a mutation at the P10 position (Ala436 to Thr). Like most serpins with hinge region mutations (P14, P12, P10), C1 inhibitor(Mo) loses its inhibitory activity. However, unlike the other hinge region mutations, this mutant is not converted to a substrate. As shown by nondenaturing gel electrophoresis, gel filtration, sucrose density gradient ultracentrifugation, and electron microscopy, C1-inhibitor(Mo) exists in both monomeric and multimeric forms. Polymerization probably results from reactive center loop insertion into the A sheet of an adjacent molecule. Native C1 inhibitor(Mo) was shown to have a thermal stability profile intermediate to those of intact and of cleaved normal C1-inhibitor. Native C1-inhibitor(Mo) did not bind to monoclonal antibody KII, which binds only to reactive center-cleaved normal C1-inhibitor. It did, however, react with monoclonal antibody KOK12, which recognizes complexed or cleaved C1-inhibitor but not intact normal C1-inhibitor. Native C1-inhibitor(Mo), therefore, exists in a conformation similar to the complexed form of normal C1-inhibitor. PMID- 8349687 TI - Interferon-gamma induces receptor dimerization in solution and on cells. AB - The extracellular domain (ECD) of the human interferon-gamma (IFN gamma) receptor was stably expressed in Chinese hamster ovary cells and purified to homogeneity. Scatchard analysis of 125I-IFN gamma binding to ECD preparations revealed the formation of a ligand-receptor complex which displayed a Ka of 6.4 +/- 0.9 x 10(8) M-1. Two types of complexes were identified by sucrose density gradient ultracentrifugation. The stoichiometry of the major ECD-ligand complex was determined by high performance liquid chromatography gel filtration. When IFN gamma was incubated with a 2-fold molar excess of ECD, a 190-kDa complex was isolated that contained 2 mol of ECD per 1 mol of IFN gamma. IFN gamma also induced dimerization of IFN gamma receptors expressed at the cell surface as detected by chemically cross-linking receptor bound ligand and analyzing cell lysates by SDS-polyacrylamide gel electrophoresis and immunoblotting. Finally, labeled forms of ECD bound to cells preincubated at 4 degrees C with excess amounts of IFN gamma indicating that the ligand could associate with more than one receptor molecule in the absence of chemical cross-linking agents. These results demonstrate that IFN gamma effects dimerization of its receptor under physiologic conditions and suggest that IFN gamma receptor dimerization may be an important event in inducing IFN gamma-dependent biologic responses. PMID- 8349688 TI - Guanine nucleotide-specific phosphate transfer by guanine nucleotide-binding regulatory protein beta-subunits. Characterization of the phosphorylated amino acid. AB - One major substrate protein was phosphorylated with [gamma-32P]GTP in membranes of human leukemia (HL-60) cells. The phosphoprotein comigrated with beta-subunits of heterotrimeric GTP-binding proteins (G proteins) in different gel systems. Upon solubilization of the phosphorylated membranes, the phosphoprotein could be immunoprecipitated by a G protein beta-subunit-specific antiserum. The beta subunit phosphorylation was transient and was found to be specific for GTP and its analog, guanosine 5'-O-(gamma-thio)triphosphate. When phosphorylated membranes were incubated with various nucleotides, the bound phosphate was specifically removed by GDP, suggesting that the phosphate can be retransferred onto GDP. Divalent cations, preferentially Mg2+ and Mn2+, were required for both phosphorylation and dephosphorylation. The phosphorylation was stable against treatment with NaOH but sensitive to treatment with heat, HCl, and hydroxylamine. Moreover, treatment of the membranes with the histidine-modifying agent, diethyl pyrocarbonate, resulted in a loss in phosphate incorporation. The data suggest that G protein beta-subunits are involved in a guanine nucleotide-specific enzymatic activity transferring the gamma-phosphate from GTP to GDP, presumably at G protein alpha-subunits, via a phosphohistidine intermediate. PMID- 8349689 TI - Nonenzymatic glycation alters protein structure and stability. A study of two eye lens crystallins. AB - We have investigated the effect of nonenzymatic glycation (fructation) in vitro on the structure and stability of two proteins that are glycated in vivo as a consequence of high endogenous levels of sugar. We find that whereas fructation leads to the structural destabilization of the monomeric gamma-crystallin from the core of the eye lens, it leads to an increase in stability in the multimeric alpha-crystallin of the lens cortex. Thus, while glycated gamma-crystallin shows (a) a longer wavelength of fluorescent emission, indicating a greater exposure of its aromatic side chains to the medium; (b) a reduced secondary structural content; and (c) a more facile denaturation by thermodynamic and chemical means, alpha-crystallin displays the opposite behavior. Furthermore, alpha-crystallin shows an increased tendency toward multimeric aggregation upon fructation. We interpret these differences in the broad context of the effects of neutralization of positive charges on protein structure and stability. Fructation tends to destabilize gamma-crystallin, by effecting a significant reversal in the balance of charges in the protein, at physiological pH. alpha-Crystallin is a multimeric protein whose pI is lower than its pH of optimum stability. Fructation in this case effectively neutralizes the cationic charges and promotes conformational order. This study indicates that although glycation brings about similar changes in the covalent chemical structures of proteins, its influence on the three dimensional structures of different proteins can be different. PMID- 8349690 TI - Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. AB - Rab proteins comprise a family of small GTPases that serve a regulatory role in membrane traffic. These proteins are in part cytosolic and in part associated with the membranes of specific exocytic and endocytic organelles. Smg p25A/rab3A GDI, a cytosolic protein which inhibits the dissociation of GDP from smg p25A/rab3A, Sec4p, and rab11, has also been found to prevent association of rab3A with the membrane. In this study, we have used Madin-Darby canine kidney cells permeabilized with the bacterial toxin streptolysin O to test the general activity of rab3A GDI in modulating the membrane association of various small GTP binding proteins. Rab3A GDP dissociation inhibitor (GDI) removed from the membrane all rab proteins we have tested and inhibited the membrane binding of in vitro translated rab proteins. However, rab3A GDI had a limited effect on the membrane association of a mutant rab5 protein which contained a farnesylated cysteine motif. Finally, we found that, although rab3A GDI resides primarily in the cytosol, it is also associated with compartments of the exocytic and endocytic pathways. Since rab3A GDI can modulate the membrane association of various rab proteins, we propose to rename it rab GDI. PMID- 8349691 TI - Phosphorylation of the insulin receptor substrate IRS-1 by casein kinase II. AB - IRS-1, a principal substrate of the insulin receptor, is phosphorylated on serine, threonine, and tyrosine residues in a variety of tissues during insulin stimulation. Casein kinase II, an insulin-sensitive serine/threonine kinase, catalyzed the in vitro incorporation of 1 to 2 mol of phosphate/mol of recombinant rat IRS-1. Two-dimensional phosphopeptide mapping of IRS-1 phosphorylated by casein kinase II in vitro and IRS-1 immunoprecipitated from intact Chinese hamster ovary cells demonstrated multiple common phosphopeptides, suggesting that overexpressed IRS-1 is a substrate for casein kinase II in these cells. Moreover, the common phosphopeptides that appeared to be insulin-sensitive in intact cells comprised 22% of casein kinase II-catalyzed 32P incorporation into IRS-1 in vitro. These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. By using phosphoamino acid analysis, strong cation exchange analysis, manual Edman degradation, and automated amino acid sequencing, Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1. Furthermore, Ser-99, an additional site labeled at low yield, appeared to be contained in an insulin-sensitive phosphopeptide. Thus, casein kinase II catalyzed phosphorylation of IRS-1 may be a component of the intracellular insulin signalling cascade. PMID- 8349692 TI - Multiple domains of the N-formyl peptide receptor are required for high-affinity ligand binding. Construction and analysis of chimeric N-formyl peptide receptors. AB - Binding of the chemotactic tripeptide fMet-Leu-Phe (fMLP) to its receptor on phagocytes activates these cells through a G protein-coupled pathway. To delineate the structural requirement of the N-formyl peptide receptor (FPR) for ligand binding and signaling, we constructed chimeric receptors between FPR and a recently identified granulocyte receptor, FPR2 (Ye, R. D., Cavanagh, S. L., Quehenberger, O., Prossnitz, E. R., and Cochrane, C. G. (1992) Biochem. Biophys. Res. Commun. 184, 582-589). FPR2 shares 69% sequence homology with the FPR; yet it binds fMLP with a low affinity (Kd = 430 nM), as compared with the high affinity (Kd = 1 nM) displayed by the FPR. This property of the FPR2 was utilized for mapping the FPR ligand binding domains. Seven chimeric FPR/FPR2 receptors were generated by sequential replacement of the FPR segments with the corresponding regions from FPR2. Three reciprocal FPR2/FPR chimeric receptors were also constructed by selective substitution of the FPR segments into FPR2. These chimeric receptors were stably expressed in transfected fibroblasts and analyzed for their ligand binding and transmembrane signaling properties. Replacement of the FPR domains, including the first and the third extracellular loops, resulted in 275- and 85-fold decrease in ligand binding affinity, respectively. Introduction of both domains into the FPR2 significantly increased ligand binding affinity (Kd = 18 nM), whereas substitution of the domains containing the first or third extracellular loop alone improved ligand binding to a lesser degree (Kd = 90 and 372 nM, respectively). In contrast, substitution of either the amino or the carboxyl-terminal regions with those of the FPR2 had little effect on ligand binding affinity. An analysis of the sequences of the two receptors revealed several key residues in the first and the third extracellular loops of the FPR and their adjacent transmembrane domains that may be essential for binding of fMLP. We propose that multiple domains of the FPR are required for high-affinity ligand binding, with a major determinant located in the first extracellular loop and its adjacent transmembrane domains. PMID- 8349693 TI - Rhodopsin is the major in situ substrate of protein kinase C in rod outer segments of photoreceptors. AB - Phorbol ester treatment of 32P-labeled retinas results in a light-dependent alteration in the phosphorylation state of rhodopsin. Previously we reported that phorbol myristate acetate causes an increase in the phosphorylation state of rhodopsin in retinas exposed to a brief flash of light, with the greatest increase in phosphorylation observed at lower (< or = 10%) bleach levels (Newton, A. C., and Williams, D. S. (1991) J. Biol. Chem. 266, 17725-17728). Here we show that phorbol myristate acetate causes a decrease in the phosphorylation of rhodopsin after exposure to levels of illumination that result in maximal bleaching of the visual receptor. In contrast, no rhodopsin phosphorylation is detected in control or phorbol ester-treated retinas in the dark. Partial proteolysis revealed that phorbol esters alter the phosphorylation of the carboxyl-terminal domain of rhodopsin. Rhodopsin is the major protein whose phosphorylation state is affected significantly by phorbol esters in situ, although a number of rod outer segment cytosolic and membrane proteins are phosphorylated by protein kinase C in vitro. Our data indicate that a major target of protein kinase C in rod outer segments is rhodopsin. PMID- 8349694 TI - Platelet-derived growth factor increases the turnover of GTP/GDP on ras in permeabilized fibroblasts. AB - The potent mitogen platelet-derived growth factor (PDGF) induced a rapid increase in Ras.GTP in permeabilized human and murine fibroblasts. The effect was initiated by both PDGF-AA acting exclusively through PDGF alpha-receptors, and by PDGF-BB interacting with both alpha- and beta-type receptors. The dose-response curves suggest that both receptor types mediate the response. PDGF-dependent Ras activation, measured as increased formation of Ras.GTP, was rapid and reversible. At 37 degrees C the effect had a duration of around 10 min. The PDGF-dependent increase in Ras.GTP was followed by a simultaneous increase in Ras.GDP. Under no experimental condition could a relative increase in Ras.GTP be detected. 0.5 microM GDP and 0.5 microM GTP were equally potent competing for the formation of Ras.[alpha-32P]GTP upon PDGF stimulation. Furthermore, when the basal nucleotide exchange rate on Ras was elevated by omission of Mg2+ from the medium, PDGF had no further effect on the formation of Ras.GTP. We therefore conclude that PDGF activates Ras through a mechanism leading to an increased nucleotide exchange on Ras. PMID- 8349695 TI - Ebulin 1, a nontoxic novel type 2 ribosome-inactivating protein from Sambucus ebulus L. leaves. AB - A novel type 2 ribosome-inactivating protein (RIP) that we named ebulin 1 has been isolated from leaves of Sambucus ebulus L. (Caprifoliaceae). In vitro ebulin 1 strongly inhibited protein synthesis by rabbit reticulocyte lysates, rat brain, and rat liver cell-free systems but did not affect in vitro plant nor bacterial protein synthesis. Ebulin 1 is composed of two subunits, a catalytic A subunit (M(r) 26,000) and a D-galactose-binding lectin B subunit (M(r) 30,000). Amino terminal amino acid sequence homology revealed the novelty that the ebulin 1 A chain shares a high degree of homology not with the A-chain of other type 2 RIPs but rather with the Cucurbitaceae type 1 RIP briodin S and the anti-human immunodeficiency virus type I proteins trichosanthin and TAP 29. Upon treatment with acid aniline the rRNA from ebulin 1-treated rabbit reticulocyte ribosomes released the RNA fragment which is diagnostic of RIP catalytic action. Ebulin 1 was nontoxic to mice up to 2 mg/kg of body weight and did not inhibit protein synthesis in cultured NHC human epithelial cells which are highly sensitive to ricin. PMID- 8349696 TI - Regulation of atrial natriuretic peptide clearance receptors in mesangial cells by growth factors. AB - Rat mesangial cells can express both 130-kDa guanylyl cyclase-coupled and 66-kDa non-coupled atrial natriuretic peptide (ANP) receptors (ANPR-A and ANPR-C, respectively). Exposure of mesangial cells, grown in 20% fetal calf serum, to 0.1% serum for 24 h increased total ANP receptor density more than 2-fold (Bmax = 87 versus 37 fmol/mg of cell protein) without changing binding affinity (Kd = 94 versus 88 pM). Radioligand binding and cross-linking studies demonstrated that up regulation of ANP binding after serum deprivation was entirely due to an increase in ANPR-C, with little or no change in ANPR-A. Inhibition of protein synthesis with cycloheximide blocked up-regulation after serum deprivation. Steady-state ANPR-C mRNA level was increased 15-fold by serum deprivation, as judged by Northern blotting. There was no change in ANPR-A mRNA. Platelet-derived growth factor and phorbol myristate acetate, when added to low serum medium, blocked or reversed the effect of serum deprivation on ANPR-C. We conclude that synthesis and expression of ANPR-C but not ANPR-A is suppressed by serum, platelet-derived growth factor, and phorbol myristate acetate. Suppression of ANPR-C in vivo could contribute to mesangial cell proliferative responses to growth factors. PMID- 8349697 TI - Mutations in the carboxyl-terminal propeptide of the pro alpha 1(I) chain of type I collagen result in defective chain association and produce lethal osteogenesis imperfecta. AB - Fibroblast cell strains from three infants with perinatal lethal osteogenesis imperfecta (OI) carry unique mutations in COL1A1 (the gene encoding the pro alpha 1(I) chain of type I procollagen) that impair chain association. The three mutations are: substitution of arginine for leucine at position 170 in the carboxyl-terminal propeptide, substitution of histidine for aspartic acid at position 59 of the propeptide, and a 6-base pair deletion that results in loss of 2 amino acid residues, glutamic acid and tyrosine, at positions 119 and 120 of the propeptide. In each cell strain the rate of association of the abnormal chain into molecules is slowed and formation of interchain disulfide bonds is impaired. The substitution at residue 59 alters the most highly conserved region of the propeptide and has a much greater effect on the incorporation of pro alpha 2(I) chains into disulfide-bonded trimers than the other two mutations. The molecules that contain the abnormal chains are extensively overmodified by post translational modifying enzymes, yet have a normal thermal stability. These findings extend the range of lethal mutations in the type I collagen genes and help to identify regions of the carboxyl-terminal propeptide that may be important for chain-chain recognition and molecular assembly. PMID- 8349698 TI - BiP binds type I procollagen pro alpha chains with mutations in the carboxyl terminal propeptide synthesized by cells from patients with osteogenesis imperfecta. AB - Of 20 fibroblast cell strains from patients with osteogenesis imperfecta (OI), a disease caused by mutations in the genes encoding type I procollagen, three had increased synthesis of BiP (GRP78), an hsp70-related, endoplasmic reticulum resident protein. All three strains carry unique mutations in pro alpha 1(I) chains which impair type I procollagen chain association. Immunoprecipitation and pulse-chase experiments show that BiP (immunoglobulin heavy chain-binding protein) stably binds pro alpha 1(I) chains in these three cell strains after a brief lag. Ascorbate, which increases procollagen synthesis, increases BiP synthesis and content in these three strains and not in the others. In one of these three strains, BiP content is constitutively elevated prior to ascorbate treatment, and BiP is less inducible. This strain also has relatively high levels of synthesis and content of GRP94, another endoplasmic reticulum-resident stress protein. Pretreating each of the three cell strains to increase their BiP content reduces subsequent ascorbate-mediated BiP induction. BiP synthesis in the 17 other OI strains examined, which had a variety of type I procollagen mutations, was normal. These results suggest that BiP is induced by and binds procollagen with specific types of mutations: ones in the carboxyl-terminal propeptide that interfere with chain association. The recognition by BiP of such procollagen in OI cell strains shows that BiP plays a role in the physiological response to the production of some disease-producing abnormal proteins. PMID- 8349699 TI - N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their orientations in the endoplasmic reticulum. AB - Using site-directed mutagenesis, we have determined that Asn68, Asn144, and Asn410 of ovine prostaglandin endoperoxide (PGH) synthase-1 are N-glycosylated. A fourth consensus N-glycosylation sequence at Asn104 is not glycosylated. Glycosylation of PGH synthase-1 at Asn410 and at either Asn68 or Asn144 was required for expression of both the cyclooxygenase and the peroxidase activities of the enzyme. Inactive PGH synthase-1 glycosylation site mutant proteins do not appear to achieve their native conformations. However, the native enzyme, once in an active conformation, does not appear to require attached carbohydrate for cyclooxygenase or peroxidase activities. N-Glycosylation consensus sequences corresponding to the three glycosylation sites of ovine PGH synthase-1 are conserved in the deduced amino acid sequences of PGH synthases-2. Using site directed mutagenesis, we determined that there is an additional site of N glycosylation in murine PGH synthase-2 located at Asn580. This site is N glycosylated in about 50% of PGH synthase-2 molecules, resulting in two peptide bands on SDS-polyacrylamide gel electrophoresis (72 and 74 kDa). Glycosylation of PGH synthase-2 is necessary for expression of enzyme activity, but glycosylation of PGH synthase-2 at Asn580 per se does not affect activity. Assuming that the N glycosylation sites of PGH synthase-1 are on the luminal side of the endoplasmic reticulum (ER), and that the site of tryptic cleavage of ovine PGH synthase-1 (Arg277) is on the cytoplasmic side of the ER, we propose that both the NH2 and COOH termini of PGH synthase-1 are located in the lumen of the ER and that there are two transmembrane domains located between Asn144 and Arg277 and between Arg277 and Asn410, respectively. A similar orientation is predicted for PGH synthase-2. PMID- 8349700 TI - Covalent modification of proteins by arachidonate and eicosapentaenoate in platelets. AB - The posttranslational modification of proteins by fatty acids has been shown to involve long chain-saturated fatty acids, predominantly palmitate. In the present study, we demonstrated by metabolic labeling of human platelets with [3H]arachidonate and [3H]eicosapentaenoate that these polyunsaturated fatty acids can also become covalently linked to proteins. The extent of binding of arachidonate to proteins was somewhat less than that of palmitate. Arachidonate binding to platelet proteins was not significantly influenced by the inhibition of cyclooxygenase and lipoxygenase. This finding and the high performance liquid chromatography analysis of radiolabeled products removed from proteins by selective cleavage techniques established that arachidonate, and not its metabolic products, was the protein-linked radiolabeled moiety in [3H]arachidonate-labeled platelets. A 7.5-fold higher concentration of unlabeled palmitate competed to a small extent with [3H] arachidonate for protein labeling. Both arachidonate and eicosapentaenoate were bound to proteins almost exclusively through ester linkages. It was further demonstrated that 61 and 66% of total protein-linked arachidonate and eicosapentaenoate, respectively, were bound via thioester bonds. In contrast, 91% of the binding of palmitate to proteins occurred via thioester linkages. As demonstrated by SDS-polyacrylamide gel electrophoresis and fluorography, the patterns of palmitoylated and arachidonoylated proteins were similar but not identical, with selected proteins only palmitoylated or only arachidonoylated. [3H]Eicosapentaenoate labeled the same set of proteins as [3H]arachidonate. The fluorographic pattern of 3H arachidonoylated proteins was not changed by cyclooxygenase and lipoxygenase inhibitors. The binding of a polyunsaturated fatty acid to a protein in place of a saturated fatty acid could significantly influence the hydrophobic interactions of the protein and, thereby, have important functional implications. PMID- 8349701 TI - Specific binding of heterogeneous ribonucleoprotein particle protein K to the human c-myc promoter, in vitro. AB - A homopurine/homopyrimidine-like sequence is found 100-150 base pairs upstream of the human c-myc promoter P1. This element, termed the CT-element, has been shown to augment expression from P1, and it serves as a positive transcriptional element when coupled to a heterologous promoter in vivo and in vitro. Synthetic oligonucleotides comprising this element were used to form DNA-protein complexes in electrophoretic mobility shift assays. By using conventional and affinity methods, 61- and 34-kDa proteins were shown to be associated with these complexes. Amino acid sequence analysis and immunological methods have identified these proteins as heterogeneous ribonucleoprotein particle (hnRNP) proteins K and A1. Surprisingly, hnRNP protein K binds to the pyrimidine-rich strand of the CT element in a sequence-specific manner as well as to the double-stranded molecule. Cotransfection of vectors encoding hnRNP protein K in the sense or anti-sense orientations with reporter plasmids driven by wild-type or mutant CT-elements demonstrates that hnRNP protein K augments gene expression in a cis-element dependent manner. Taken together, these results suggest that hnRNP protein K may play a role in the transcriptional regulation of the human c-myc gene. PMID- 8349702 TI - Structure/function relationships in hexokinase. Site-directed mutational analyses and characterization of overexpressed fragments implicate different functions for the N- and C-terminal halves of the enzyme. AB - Hexokinases are comprised of two highly homologous approximately 50-kDa halves and are product-inhibited by glucose-6-P. Four amino acid residues, Ser603, Asp657, Glu708, and Glu742, located in the C-terminal half of the tumor mitochondrial enzyme have been shown to be essential for enzyme function (Arora, K. K., Filburn, C. R., and Pedersen, P. L. (1991) J. Biol. Chem. 266, 5359-5362). Here we have assessed also the role of the N-terminal half of the same enzyme. Site-directed mutagenesis of residues predicted to interact with glucose in the N terminal half, i.e. Ser155, Asp209, and Glu260, to Ala, have no effect on hexokinase activity. In addition, inhibition by hexose mono- and bisphosphates is unchanged for each of the mutant enzymes. Significantly, the overexpressed N terminal polypeptide is devoid of catalytic activity but does have the capacity to bind ATP-agarose and be released with ATP and glucose-6-P. In contrast, the overexpressed C-terminal polypeptide is catalytically active and shows the same product inhibition pattern as the complete 100-kDa parent enzyme. These results emphasize that the N-terminal half of tumor hexokinase is essential neither for catalysis nor product modulation. Rather, the N-terminal half may play another role, perhaps in modulation of the ATP/glucose-6-P-dependent binding of the enzyme to tumor mitochondria or by acting as a spacer between the outer mitochondrial membrane and the C-terminal catalytic unit. PMID- 8349703 TI - Requirement of phenylalanine 343 for the preferential delta 4-lyase versus delta 5-lyase activity of rat CYP17. AB - Site-directed mutagenesis of a domain (amino acids 343-348) within the conserved region of rat CYP17 was performed to investigate species-specific differences between rat and human/bovine delta 4-versus delta 5-lyase activity. This domain displays substantial deviations between the rat and human/bovine/pig sequences and includes Arg346, which is known to be essential for delta 4-lyase (Kitamura, M., Buczko, E., and Dufau, M. L. (1991) Mol. Endocrinol. 5, 1373-1380) and delta 5-lyase activities. Analysis of the delta 4-lyase activity of mutant rat CYP17 cDNA expressed in nonsteroidogenic COS-1 cells revealed that substitution of Phe at position 343 in the rat with Ile of the human/bovine sequence resulted in a reduction in delta 4-lyase activity to levels in the range of the delta 5 supported reaction. This Phe343-->Ile mutant CYP17 did not exhibit changes either in delta 5-supported lyase activity or in delta 4- and delta 5-hydroxylase activities. Substitution of Asn344, Ser347, and His348 in rat CYP17 with the corresponding bovine amino acids Ser, Asn, and Arg did not enhance this effect. Thus, the reduced activity of the bovine CYP17 delta 4-lyase reaction can be mimicked in part in the rat polypeptide by the substitution of Phe343 with the bovine counterpart, Ile. Unlike the bovine CYP17-catalyzed reaction, the rat Phe343-->Ile mutant exhibited a low level lyase activity (kcat) that did not discriminate between delta 4- and delta 5-substrates. These results suggest that the presence of Phe343 enhances the delta 4-supported lyase activity possibly through stabilization of a delta 4-specific interaction. PMID- 8349704 TI - VMA13 encodes a 54-kDa vacuolar H(+)-ATPase subunit required for activity but not assembly of the enzyme complex in Saccharomyces cerevisiae. AB - Previous purifications and characterizations of the Saccharomyces cerevisiae vacuolar proton-translocating ATPase (V-ATPase) have indicated that this enzyme is a multisubunit complex composed of at least eight subunits of 100-, 69-, 60-, 42-, 36-, 32-, 27-, and 17-kDa (Kane, P. M., Yamashiro, C. T., and Stevens, T. H. (1989) J. Biol. Chem. 264, 19236-19244). We report the cloning and characterization of an additional V-ATPase subunit, the 54-kDa subunit, which is encoded by the VMA13 gene. VMA13 was isolated by complementation of the growth phenotypes associated with the vma13 mutation, which was originally described as cls11 (Ohya, Y., Umemoto, N., Tanida, I., Ohta, A., Iida, H., and Anraku, Y. (1991) J. Biol. Chem. 266, 13971-13977). The nucleotide sequence of the VMA13 gene predicted a hydrophilic polypeptide with a calculated molecular mass of 54,415 daltons. The VMA13 54-kDa gene product resides on the vacuolar membrane and co-purified with the active V-ATPase complex. Characterization of a null vma13 mutant (delta vma13) revealed that the Vma13 polypeptide is essential for V ATPase activity. However, the Vma13 polypeptide is not required for targeting of the other V-ATPase subunits (100-, 69-, 60-, 42-, 27-, or 17-kDa subunits) to the vacuolar membrane as shown by the association of these subunits with vacuolar membranes isolated from delta vma13 cells. The nature of the V-ATPase "complex" in delta vma13 mutant is, nevertheless, fundamentally different from the wild type enzyme. This is evidenced by the fact that the inactive V-ATPase complex from delta vma13 cells is less stable than the wild-type enzyme. Taken together, these results indicate that VMA13 encodes the 54-kDa subunit of the V-ATPase and that this subunit is essential for activity, but not assembly, of the enzyme complex. PMID- 8349705 TI - Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin. AB - We have cloned a human brain cholecystokinin (CCK)-B receptor cDNA and characterized its function by introducing it into Chinese hamster ovary (CHO) cells. The deduced amino acid sequence was highly conserved as compared with those of the gastrin receptors in Mastomys enterochromaffin-like cells (90%) and canine parietal cells (89%). Human brain CCK-B receptors possessed slightly but significantly higher affinities for CCK-8 than for gastrin I, while both ligands bound equally to Mastomys enterochromaffin-like cell-derived gastrin receptors. Both CCK-8 and gastrin I markedly augmented phosphoinositide hydrolysis and cytosolic free calcium levels in the CHO transfectants, indicating that the cloned CCK-B receptor could functionally couple with intracellular signaling molecules. Moreover, CCK-8 and gastrin I dose-dependently increased [3H]thymidine incorporation of the CHO transfectants in serum-free medium and promoted cell growth. The CCK-B receptor mRNA was abundantly expressed in particular areas of the human brain and stomach, such as the cerebral cortex and mucosa of the gastric fundus. This is the first demonstration of trophic effects of CCK and gastrin through the normal human brain CCK-B receptor. The availability of this receptor cDNA will help to clarify the precise role of CCK in the central nervous system as well as digestive organs. PMID- 8349706 TI - Biosynthesis of reovirus-specified polypeptides. Analysis of ribosome pausing during translation of reovirus S1 and S4 mRNAs in virus-infected and vector transfected cells. AB - The steady-state distribution of translating ribosomes on the reovirus s1 and s4 mRNAs was determined using a sensitive primer extension inhibition assay and cDNA clones of the reovirus S1 and S4 genes. Positions of significant ribosome pausing included the sites of initiation and termination of translation, both in vivo in reovirus-infected mouse fibroblast L cells and in vitro in rabbit reticulocyte lysates. The patterns of ribosome pausing detected in vivo and in vitro were comparable. Ribosomes were far less uniformly distributed along the polycistronic s1 mRNA than they were along the monocistronic s4 mRNA. During reovirus infection, ribosome pausing was detected at the initiation codons of the s1 mRNA sigma 1 and sigma 1ns open reading frames and the s4 mRNA sigma 3 open reading frame, direct evidence that initiation is a slow step of translation in vivo. Quantitative analysis of reovirus mRNA translation in infected and transfected cells suggested that ribosomes paused longer at an AUG initiation codon present in strong context than one present in weak context. These results suggest that the dynamics of ribosome movement during translation of the reovirus s1 and s4 mRNAs are similar in vivo and in vitro and that the relative ribosome pause at an AUG initiation codon may be affected by the flanking nucleotide context of the AUG codon. PMID- 8349707 TI - An antigenic polysaccharide from Campylobacter coli serotype O:30. Structure of a teichoic acid-like antigenic polysaccharide associated with the lipopolysaccharide. AB - A water-soluble antigenic polysaccharide of high M(r) associated with the lipopolysaccharide has been isolated from phenol-water extraction of cells of Campylobacter coli serotype O:30. The polysaccharide and oligosaccharide degradation products formed on O-dephosphorylation and by periodate oxidation followed by reduction have been investigated by one- and two-dimensional 1H, 13C, and 31P NMR. It is concluded that the antigenic polysaccharide has a teichoic acid-like structure with a poly-Ribitol phosphate, [5-Ribitol-1-P]n, backbone with side chains at O-2 of O-(6-deoxy-beta-D-talo-heptopyranosyl)-(1-->4)-(2 acetylamino-2-deoxy-beta-D- glucopyranosyl) units. The structure is unusual in Gram-negative bacteria and is unique in possessing 6-deoxy-D-talo-heptose as a constituent sugar. Evidence for the relationship of the antigenic polysaccharide to the lipopolysaccharide of low M(r) is discussed. PMID- 8349709 TI - The anticodon and discriminator base are important for aminoacylation of Escherichia coli tRNA(Asn). AB - A gel shift assay that distinguishes the aminoacylated form from the deacylated form of tRNAs was used to study the requirements for aminoacylation of Escherichia coli tRNA(Asn) in vivo. tRNA(Asn) derivatives containing single base changes in their anticodons or discriminator bases were constructed, and the extent of in vivo aminoacylation was determined directly. Substitution of U35 with C35 or U36 with C36 abolished aminoacylation of the tRNA. Substitution of G34 with C34 converted tRNA(Asn) into a lysine acceptor. Thus, each of the anticodon nucleotides are important for aminoacylation of tRNA(Asn). Substitution of discriminator base G73 with A73 affected the extent of aminoacylation in vivo indicating that the discriminator base also contributes to aminoacylation of tRNA(Asn). PMID- 8349708 TI - Heparin-binding epidermal growth factor-like growth factor expression in cultured fetal human vascular smooth muscle cells. Induction of mRNA levels and secretion of active mitogen. AB - Heparin-binding EGF-like growth factor (HB-EGF) is a recently identified potent mitogen for smooth muscle cells (SMC). To explore whether SMC can also synthesize HB-EGF, cultured fetal human vascular SMC (FHVSMC) were analyzed for the production of HB-EGF mRNA and active growth factor. It was found that in FHVSMC, HB-EGF has the characteristics of an early response gene in that (i) the addition of fresh 10% fetal calf serum to serum-starved FHVSMC led to a rapid and transient rise in HB-EGF mRNA levels with a maximal induction of 12-14-fold occurring within 2-4 h, (ii) the phorbol ester, 12-O-tetradecanoylphorbol-13 acetate (TPA) also elevated HB-EGF mRNA levels rapidly and transiently with a maximal induction of 7-8-fold occurring at 2-4 h, and (iii) cyclohexamide at 40 micrograms/ml markedly increased basal, serum-, and TPA-induced HB-EGF mRNA levels. In addition, HB-EGF mRNA levels were increased 7-11-fold by addition of either HB-EGF itself, platelet-derived growth factor, or basic fibroblast growth factor, all potent SMC mitogens. Besides synthesizing HB-EGF mRNA, FHVSMC were found to release into conditioned medium a bioactive HB-EGF-like protein that cross-reacted with anti-HB-EGF antibody. PMID- 8349710 TI - Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. AB - Axial pattern formation is sustained in the mammalian gut epithelium despite rapid and continuous renewal of its four principal cell lineages. The mouse and rat liver fatty acid-binding protein (L-FABP) genes (Fabpl) represent an excellent model for understanding the mechanisms that determine differentiation dependent, cell lineage-specific, and distinct regional patterns of expression along the crypt-to-villus and duodenal-to-ileal axes of the gut, as well as within the liver acinus. We have used transgenic mice to map cis-acting elements in rat Fabpl that control these patterns of gene expression. Seven transgenes were analyzed, representing sequential deletions of the 5'-nontranscribed domain of Fabpl linked to the human growth hormone (hGH) gene beginning at its nucleotide +3 (L-FABP/hGH+3). Several pedigrees of mice containing each one of the L-FABP/hGH+3 transgenes were examined at the end of their 8th and 20th weeks of postnatal life using immunocytochemical and RNA hybridization analyses. A remarkably compact sequence spanning nucleotides -132 to +21 of Fabpl is sufficient to establish and maintain a distribution of reporter mRNA and protein in villus-associated enterocytes located along the duodenal-to-ileal axis of the gut that resembles the pattern of expression of the endogenous Fabpl gene. L-FABP 132 to +21/hGH+3 is also expressed in surface and pit mucous cells of gastric units and in enterocytes located in the colonic homologs of small intestinal villi, the surface epithelial cuffs. This pattern of transgene expression in the stomach and colon recapitulates that of the intact endogenous donor rat Fabpl but not that of mouse Fabpl, which is silent in these proximal and distal segments of the gastrointestinal tract. Analysis of mice containing L-FABP-4000 to +21/hGH+3, L-FABP-1600 to +21/hGH+3, L-FABP-596 to +21/hGH+3, L-FABP-246 to +21/hGH+3, and L FABP-186 to +21/hGH+3 indicate that Fabpl's cephalocaudal gradient is influenced by cis-acting suppressors of cecal and colonic expression located between nucleotides -4000 and -1600 and by cis-acting activators of cecal and colonic expression located between nucleotides -597 and -351. L-FABP-132 to +21/hGH+3 is precociously activated in proliferating and nonproliferating epithelial cells located in intestinal crypts. The suppressor(s) of L-FABP accumulation in crypt epithelial cell populations are not represented between nucleotides -4000 and +21, indicating that different cis-acting sequences regulate regional and differentiation-dependent patterns of Fabpl expression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8349711 TI - Functional consequences of alterations to hydrophobic amino acids located in the M4 transmembrane sector of the Ca(2+)-ATPase of sarcoplasmic reticulum. AB - Those hydrophobic residues between Ile298 and Ile315 in transmembrane segment M4 of the Ca(2+)-ATPase of sarcoplasmic reticulum, not previously mutated, were mutated systematically in ways that would alter their size or polarity, and functional consequences were measured. Fourteen residues in this sequence are organized as juxtapositions of large, hydrophobic (Val, Leu, Ile) and small (Ala, Gly) residues, and these were altered so that large residues were substituted for small and vice versa. Several mutants exhibited diminished Ca2+ transport, but mutants A305V and A306V lost all Ca2+ transport function. In both cases, the mutants were phosphorylated with ATP in the presence of Ca2+ and with inorganic phosphate only in the absence of Ca2+, indicating that the Ca(2+)-binding sites were intact. Reduced Ca2+ affinity, as measured by Ca2+ dependence of phosphorylation from ATP, was observed for mutant A305V. In both mutants, the ADP insensitive phosphoenzyme intermediate (E2P) decayed slowly relative to the wild type enzyme, suggesting that the E2P to E2 conformational transition was impaired, slowing the rate of the phosphatase reaction. Double mutants which reversed the order of Val304 and Ala305 and Ala306 and Ile307, resulted in the same phenotype as the single Ala mutations. These results, combined with our previous demonstration that Glu309 is a Ca2+ binding residue, that Pro312 is involved in E1P to E2P conformational changes, and that Gly310 is involved in E2P to E2 conformational changes, support the hypothesis that transmembrane segment M4 plays a key role in the Ca2+ transport function of the Ca(2+)-ATPase through its involvement in both the binding of Ca2+ and the subsequent conformational changes which bring about the translocation of Ca2+ to the lumen of the membrane. PMID- 8349713 TI - The multiple roles for ATP in the Escherichia coli UvrABC endonuclease-catalyzed incision reaction. AB - The biochemical properties of the Escherichia coli UvrA tandem ATPase site mutants in nucleotide excision repair have been studied. In these and earlier studies it was found that ATP binding is required for protein-protein and nucleoprotein association reactions, whereas the dissociation reactions are driven by the hydrolysis of ATP. The self-association of UvrA to form the reactive dimeric species UvrA2 is driven by nucleotide binding, but its dissociation from DNA requires ATP hydrolysis. Similarly, ATP binding drives those allosteric changes in DNA topology during UvrA2-nucleoprotein formation (Oh, E.Y., and Grossman, L. (1986) Nucleic Acids Res. 14, 8557-8571). The manifestation of the UvrB-associated cryptic ATPase requires UvrA and DNA in a helicase-catalyzed supercoiling reaction. The UvrA2B helicase activity requires ATP hydrolysis by the C-terminal ATPase site of UvrA in addition to UvrB. ATP hydrolysis by the C-terminal ATPase site of UvrA also participates in the localization of damaged sites contributing to the formation of damage-specific high affinity nucleoprotein complexes. The levels of complementation to UV survival by the ATPase site mutants of UvrA (Thiagalingam, S., and Grossman, L. (1991) J. Biol. Chem. 266, 11395-11403) correspond to its ability to self-bind and translocate in combination with the UvrB subunit in its search for damaged sites during the preincision mode of nucleotide excision. PMID- 8349712 TI - The structures and biological activities of the lipo-oligosaccharide nodulation signals produced by type I and II strains of Bradyrhizobium japonicum. AB - Bradyrhizobium japonicum produces lipo-oligosaccharide signal molecules that induce deformation of root hairs and meristematic activity on soybeans. B. japonicum USDA135 (a Type I strain) produces modified chitin pentasaccharide molecules with either a terminal N-C16:0- or N-C18:1-glucosamine with and without an O-acetyl group at C-6 and with 2-O-methylfucose linked to C-6 of the reducing N-acetylglucosamine. An additional molecule has N-C16:1-glucosamine and no O acetyl group. All of these molecules cause root hair deformation on Vicia sativa and Glycine soja. The C18:1-containing molecules were tested and found to induce meristem formation on G. soja. USDA61 (a Type II strain) produces eight additional molecules. Five have a carbamoyl group on the terminal N acylglucosamine. Six have chitin tetrasaccharide backbones. Three have a terminal N-acyl-N-methylglucosaminosyl residue. In four molecules, the reducing-end N acetylglucosamine is glycosidically linked to glycerol and has a branching fucosyl, rather than a 2-O-methylfucosyl, residue. One molecule has a terminal N acylglucosamine that has both acetyl and carbamoyl groups (one each). PMID- 8349714 TI - Role of microtubules in transferrin receptor transport from the cell surface to endosomes and the Golgi complex. AB - Transferrin receptor (TfR) follows complex pathways of transport after endocytosis from the cell surface. Most TfR is transported to endosomes and returns rapidly to the cell surface. In addition, approximately 10% of the internalized receptor recycles through the Golgi complex. To examine the role of microtubules in TfR traffic, K562 cultured human leukemia cells treated with nocodazole to depolymerize microtubules were studied. Nocodazole caused a 50% increase in the level of surface TfR, which was due to a change in receptor dynamics. The endocytosis rate in treated cells was 20% of control, indicating that TfR endocytosis via clathrin-coated vesicles was slowed, whereas the recycling of internalized receptors to the cell surface was unaffected. In contrast, nocodazole had little effect on the transport of TfR from the cell surface to the Golgi complex. Thus, the fragmentation and dispersal of the Golgi complex caused by microtubule depolymerization, which does not interrupt secretory traffic through this organelle, also does not block recycling through the Golgi. The decreased TfR endocytosis via coated vesicles and the increased TfR transport to the Golgi caused by nocodazole suggest that either (i) endocytosis via coated vesicles is not the rate-limiting step in transport to the Golgi or (ii) coated vesicles are not a part of this pathway. Finally, because nocodazole inhibits traffic from endosomes to lysosomes, surface-to-Golgi transport probably does not involve a lysosomal intermediate. PMID- 8349715 TI - A video-based system for the estimation of the inertial properties of body segments. AB - A system for the estimation of the inertial properties of human body segments using advanced video technology and computer image processing was developed. The system is based on the photogrammetric technique, where three-dimensional information is determined from two separate two-dimensional video images. The inertial properties are calculated using an image-processing algorithm which provides volumetric information, coupled with a database of anatomical densities provided in the literature. In order to determine the accuracy of the system and its limitations, the system estimates of the inertial properties of solid bodies were compared to theoretically calculated values. The application of the system to kinesiological studies is illustrated by measuring the inertial properties of the shank of three subjects, and comparing the results to data generated using regression equations provided in the literature. Human factors, such as segment boundaries identification and color thresholds selection, were found to introduce the largest errors. A proper selection of the optical setting can reduce the errors to levels of 5% or better. On the average, the system overestimated the inertial properties of solid objects by 2.51% for mass, 1.21% for center of mass, 4.53% for transverse moments of inertia and 3.65% for longitudinal moment of inertia. The video-based estimates of the mass and center of mass of the shank were comparable to values obtained from anthropometric-based regression equations. The predictions of the transverse moment of inertia of the shank varied considerably among the methods. The findings suggest that a video-based system represents a promising technique for estimating inertial properties of human body segments for individual subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349717 TI - Sagittal-plane mobility of the cat cervical spine. AB - The present study was conducted to evaluate the nature of sagittal-plane motion across cervical vertebral joints and to identify the centers of rotation for each joint in anaesthetized cats X-rayed in a range of head-neck postures. Relative positions of adjacent pairs of vertebrae were assessed by constructing transparent templates for each vertebra that could be overlaid onto different X rays, and then by digitizing the locations of three markers attached at a distance from each template. The finite centers of rotation for each joint were estimated using a rigid-body method. The errors associated with the estimates were quantified further by using a method in which the positions of digitized markers were fitted to concentric circles using a least-squares approach. The center of rotation between the skull and C1 was located at the cranial articular facets between the two bones. The center of rotation between C1 and C2 was situated near the tip of the odontoid process close to the site of attachment of the transverse ligaments. Centers of rotation for the other cervical vertebral joints were located in the region of the intervertebral disc. A similar range of values was obtained for centers of rotation when extended or flexed postures were used for the calculations, suggesting that the centers of rotation may not move markedly throughout a range of sagittal-plane rotations of approximately 90 degrees at the skull-C1 joint and about 15-30 degrees at the other cervical joints. These results showed that all cervical joints rotated during sagittal plane motion. A minimal representation of the musculoskeletal mechanics of the feline neck probably requires multiple segments, each corresponding to a single vertebral bone. PMID- 8349716 TI - Effects of arch height of the foot on angular motion of the lower extremities in running. AB - It has been suggested that a relationship exists between the height of the medial longitudinal arch of the foot and athletic injuries to the lower extremities. However, the functional significance of arch height in relation to injury is not well understood. The purpose of this study was to determine the influence of arch height on kinematic variables of the lower extremities that have been associated with the incidence of injury in running in an attempt to gain some insight into a functional relationship between arch height and injury. The three-dimensional kinematics of the lower extremities were measured during running for 30 subjects using high-speed video cameras. A joint coordinate system was used to calculate the three-dimensional orientation of the ankle joint complex for a single stance phase. Simple, linear regression analyses showed that arch height does not influence either maximal eversion movement or maximal internal leg rotation during running stance. However, assuming that knee pain in running can result from the transfer of foot eversion to internal rotation of the tibia, a functional relationship between arch height and injury may exist in that the transfer of foot eversion to internal leg rotation was found to increase significantly with increasing arch height. A substantial (27%), yet incomplete, amount of the variation in the transfer of movement between subjects was explained by arch height, indicating that there must be factors other than arch height that influence the kinematic coupling at the ankle joint complex. Additionally, the transfer of movement is only one factor of many associated with the etiology of knee pain in running.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349718 TI - Numerical simulation of leaflet flexure in bioprosthetic valves mounted on rigid and expansile stents. AB - Recent studies suggest that flexural stresses induced during the opening phase may be responsible for much of the mechanical failures of bioprosthetic heart valves. Sharp leaflet bending is promoted by the mounting of valves on rigid stents that do not mimic the systolic expansion of the natural aortic root. We, therefore, hypothesized that flexural stresses could be significantly reduced by incorporating a flexible or expansile supporting stent into the valve design. Using our own non-linear finite element code (INDAP) and the pre- and post processor modules of a commercial finite element package (PATRAN), we simulated the opening and closing behaviour a trileaflet bovine pericardial valve. The leaflets of this valve were assumed to be of uniform thickness, with a non-linear elastic behaviour adapted from experimentally obtained bending stiffness data. Our simulations have shown that during maximal systolic valve opening, sharp curvatures are induced in the leaflets near their commissural attachment to the supporting stent. These areas of sharp flexure experience compressive stresses of similar magnitude to the tensile stresses induced in the leaflets during valve closure. By incorporating a stent with posts that pivot about their base, such that a 10% expansion at the commissures is realized, we were able to reduce the compressive commissural stressing from 250 to 150 kPa. This was a reduction of 40%. Conversely, a simple pliable stent with stent posts that deflect inward and outward under load did not achieve a significant reduction of compressive stresses. This numerical analysis, therefore, supports the theory that (i) high flexural and compressive stresses exist at sites of sharp leaflet bending and may promote bioprosthetic valve failure, and (ii) that proper design of the supporting stent can significantly reduce such flexural stresses. PMID- 8349719 TI - Forces in gastrocnemius, soleus, and plantaris tendons of the freely moving cat. AB - The purpose of this study was to gain an insight into the mechanisms of force sharing among muscles in a functional group. Tendon force measurements were obtained simultaneously from gastrocnemius, soleus, and plantaris muscles of 10 cats during a variety of different locomotor tasks using strain gauge based force transducers. In particular, tendon forces were measured for conditions where movement speed was altered systematically, and where movement speed was kept constant but external resistance to walking was varied systematically. The results show that forces in the gastrocnemius and plantaris tendons increase with increasing intensities of movement, independent of intensity being altered by varying speed or external resistance. In contrast, peak soleus forces, on an average, remained nearly the same for all conditions; however, substantial modulations in soleus force were observed for consecutive stride cycles. These results suggest that soleus forces are not limited by peripheral (contractile) conditions but by central mechanisms and, further, that these central mechanisms depend on speed of movement and resistance to movement. PMID- 8349720 TI - Direct calculation of the surface-to-volume ratio for human cancellous bone. AB - There are many diseases which cause detrimental changes in the trabecular structure of cancellous bone, leading to mechanical failure of the tissue. One approach to understanding the mechanisms of these diseases is to create idealized models that recreate the morphology of the tissue. This paper presents a partial development of such a model. Further histological methods must be developed before a complete definition of morphologically valid models is possible. In a histological section of cancellous bone, the orientation and length of the trabecular surfaces determine how a line drawn across the bone section will intersect the bone-marrow interface. The distribution of the average length between intersections for a set of parallel lines is defined as the mean intercept length distribution. In this paper, the average surface morphology and volume of the average structure of cancellous bone is determined from an examination of the mean intercept length. The average structure of cancellous bone contains a repeated structural element (SE). As a result, the basic bone structure is analogous to a brick wall made from many similar bricks. For a group of 107 specimens, a strong relationship between structural element volume (SE.V) and bone volume fraction (BV/TV) is demonstrated, SE.V = 0.017 kappa (BV/TV)-2.05 mm3, R2 = 0.93, with kappa a model-dependent constant. For the same specimens, the structural element surface (SE.S) showed the relationship, SE.S = 0.144 kappa (BV/TV)-1.35, R2 = 0.92. As a result of the inverse square dependence of structural element volume on bone volume fraction, it is predicted that cancellous bone strength is inversely proportional to structural element volume. PMID- 8349721 TI - Hip joint loading during walking and running, measured in two patients. AB - The resultant hip joint force, its orientation and the moments were measured in two patients during walking and running using telemetering total hip prostheses. One patient underwent bilateral joint replacement and a second patient, additionally suffering from a neuropathic disease and atactic gait patterns, received one instrumented hip implant. The joint loading was observed over the first 30 and 18 months, respectively, following implantation. In the first patient the median peak forces increased with the walking speed from about 280% of the patient's body weight (BW) at 1 km h-1 to approximately 480% BW at 5 km h 1. Jogging and very fast walking both raised the forces to about 550% BW; stumbling on one occasion caused magnitudes of 720% BW. In the second patient median forces at 3 km h-1 were about 410% BW and a force of 870% BW was observed during stumbling. During all types of activities, the direction of the peak force in the frontal plane changed only slightly when the force magnitude was high. Perpendicular to the long femoral axis, the peak force acted predominantly from medial to lateral. The component from ventral to dorsal increased at higher force magnitudes. In one hip in the first patient and in the second patient the direction of large forces approximated the average anteversion of the natural femur. The torsional moments around the stem of the implant were 40.3 N m in the first patient and 24 N m in the second. PMID- 8349722 TI - Trabecular bone modulus and strength can depend on specimen geometry. AB - We performed a series of uniaxial compression tests on wet bovine trabecular bone to compare both modulus and strength when measured using 2:1 aspect ratio (10 mm long, 5 mm diameter) cylinders (n = 30) and 5 mm cubes (n = 29). We also compared the correlation coefficients in the resulting modulus-density and strength density regressions and the standard errors of the estimate. When comparing the mean values of modulus and strength for each group, the confounding variations in apparent density were accounted for with an analysis of covariance. The Fisher's Z transformation was used to compare the correlation coefficients statistically. Results from the analysis of covariance indicated that the modulus and strength of the cubes were higher by 36% (p < 0.01) and 18% (p < 0.05), respectively, with respect to the 2:1 cylinder values. The correlation coefficients in the modulus density and strength-density regressions were not sensitive to the regression model (linear versus power law). However, correlation coefficients for both modulus-density and strength-density regressions were higher (p < 0.05) for the 2:1 cylinders (r = 0.90, modulus; r = 0.94, strength) than for the cubes (r = 0.57, modulus; r = 0.82, strength). In addition, the standard errors of the estimate in both modulus and strength were substantially lower for the 2:1 cylinders. These data indicate that both modulus and strength can depend on the specimen geometry when using conventional compression testing techniques. We conclude, therefore, that inter-study comparisons of modulus and strength may be invalid if these confounding effects of different specimen geometries are not addressed. Our data also indicate that density can better explain the observed variance in modulus and strength when 2:1 cylinders are used as opposed to cubes. Using this phenomenon as a rationale for choosing a standard specimen gometry, we recommend that the 2:1 cylinder be used as a standard specimen in studies designed to determine the effects of various treatments on the uniaxial compressive modulus and strength of trabecular bone. PMID- 8349723 TI - Age and dose-dependent carcinogenic effects of N-nitrosomethylurea administered intraperitoneally in a single dose to young and adult female mice. AB - Female Swiss-derived SHR mice aged 3 ("young") and 12 months ("adult") were exposed to a single i.p. administration of N-nitrosomethylurea (NMU) at one of four doses: 0, 10, 20, or 50 mg/kg. The mean survival time of the young mice so treated was 440, 325, 398 and 182 days, and of the adult mice 221, 249, 191, and 168 days respectively. The incidence of all kinds of tumours in young mice was 40%, 64%, 77%, and 40%, of malignant tumours 33%, 43%, 57% and 20% of lung adenomas 7%, 14%, 40%, and 20% and of papillomas of the forestomach 0%, 14%, 23%, and 3% respectively. In adult mice these figures were for all kinds of tumours 52%, 52%, 56%, and 50%, for malignant tumours 44%, 52%, 52%, and 40%, for lung adenomas 7%, 0%, 8%, and 20%, for papillomas of the forestomach 0%, 0%, 12%, and 0% respectively. The exposure of adult female mice to various doses of NMU did not significantly increase the incidence of tumours or of malignant tumour incidence in comparison to age-matched controls. At the same time the latency of fatal tumours was shorter in the adult groups than in the young groups. Histoautoradiography of tissues of intact young and adult mice showed that there are no statistically significant age-related differences in the labelling index of forestomach epithelium, endometrium and lung alveolar wall epithelium. Only the labelling index of hepatocytes was decreased in the liver of adult mice in comparison to young ones. Comparison of the present experimental results with the data available on DNA synthesis and on O6-methylguanine repair in target tissues suggests a requirement for individual monitoring of age-related changes of biomarkers in exposure to carcinogenic agents. The analysis of data on the dose dependence of the carcinogenic effect of NMU against the background of a multistage model suggests an age-related accumulation of stochastically damaged cells for some tissues. PMID- 8349724 TI - Antiproliferative activity of casodex (ICI 176.334) in hormone-dependent tumours. AB - The nonsteroidal antiandrogen casodex has been described as a peripherally selective drug for the treatment of prostatic cancer. In this study we determined its activity in various models of hormone-dependent malignancies including those of the prostate and the breast. Analysis of endocrine effects in rats after 15 days of treatment revealed a strong reduction of the weights of prostates and seminal vesicles and a significant rise of testosterone serum levels as a result of the interference with central feedback mechanisms. The growth of androgen sensitive human LNCaP/FGC prostate cancer cells was strongly inhibited by casodex. Unlike hydroxyflutamide, casodex was also active in hormone-depleted medium. The inhibitory effect was overcome by addition of testosterone propionate, which indicates an androgen-receptor-mediated mode of action. In rats bearing Dunning R3327-G prostate carcinomas casodex exerted a strong antitumour effect at the beginning of therapy. However, after 4 weeks of treatment tumours resumed growth whereas diethylstilboestrol-treated tumours remained static. In MXT-M3.2 mouse mammary tumours with significant quantities of androgen receptors casodex was also effective in inhibiting tumour growth. After 6 weeks of treatment, tumour weights were reduced by 69% whereas uterine weights were significantly increased, possibly because of a progestin-like activity of the drug. Csodex is very active in various models of hormone-dependent carcinomas. However, the limited duration of action in prostatic tumours and the incomplete growth inhibition in mammary tumours suggest that it should be used only combination with other endocrine therapies. PMID- 8349725 TI - Expression of lectin-specific cellular glycoconjugates during oral carcinogenesis. AB - The binding pattern of two lectins, concanavalin A (ConA) and peanut agglutin (PNA), in various phases of tumour progression in the oral epithelium was studied. These included non-dysplastic, dysplastic and neoplastic lesions as well as normal tissue. ConA and PNA showed intense staining in the basement membrane of all types of lesions. Little difference was observed in the staining patterns between different stages of oral carcinogenesis, either with ConA or PNA. ConA showed mild cytoplasmic and membrane staining in all types of lesions while PNA showed moderate to intense staining in both the cytoplasm and membrane of lower layer cells in all histological groups. The present study therefore shows that these lectins have limited value in the elucidation of oral carcinogenesis and are of insignificant diagnostic value. PMID- 8349726 TI - Report from the 34th annual meeting of the American Society of Hematology, December 4-8, 1992. PMID- 8349727 TI - NDC1: a nuclear periphery component required for yeast spindle pole body duplication. AB - The spindle pole body (SPB) of Saccharomyces cerevisiae serves as the centrosome in this organism, undergoing duplication early in the cell cycle to generate the two poles of the mitotic spindle. The conditional lethal mutation ndc1-1 has previously been shown to cause asymmetric segregation, wherein all the chromosomes go to one pole of the mitotic spindle (Thomas, J. H., and D. Botstein. 1986. Cell. 44:65-76). Examination by electron microscopy of mutant cells subjected to the nonpermissive temperature reveals a defect in SPB duplication. Although duplication is seen to occur, the nascent SPB fails to undergo insertion into the nuclear envelope. The parental SPB remains functional, organizing a monopolar spindle to which all the chromosomes are presumably attached. Order-of-function experiments reveal that the NDC1 function is required in G1 after alpha-factor arrest but before the arrest caused by cdc34. Molecular analysis shows that the NDC1 gene is essential and that it encodes a 656 amino acid protein (74 kD) with six or seven putative transmembrane domains. This evidence for membrane association is further supported by immunofluorescent localization of the NDC1 product to the vicinity of the nuclear envelope. These findings suggest that the NDC1 protein acts within the nuclear envelope to mediate insertion of the nascent SPB. PMID- 8349728 TI - Identification and characterization of a sphere organelle protein. AB - Sphere organelles are nuclear structures in amphibian oocytes that are easily visible by light microscopy. These structures are up to 10 microns in diameter and have been described morphologically for decades, yet their function remains obscure. The present study defines a protein component of the sphere organelle, named SPH-1, which is recognized by a mAb raised against purified Xenopus laevis oocyte nucleoplasm. SPH-1 is an 80-kD protein which is localized specifically to spheres and is undetectable elsewhere on lampbrush chromosomes or in nucleoli. We show using confocal microscopy that SPH-1 is localized to the cortex of sphere organelles. Furthermore, we have isolated a cDNA that can encode SPH-1. When epitope-tagged forms of SPH-1 are expressed in X. laevis oocytes the protein specifically localizes to spheres, demonstrating that the cloned cDNA encodes the sphere antigen. Comparison of the predicted amino acid sequence with sequence databases shows SPH-1 is related to p80-coilin, a protein associated with coiled bodies; coiled bodies are nuclear structures found in plant and animal cells. The sphere-specific mAb stains X. laevis tissue culture cells in a punctate nuclear pattern, showing that spheres or sphere antigens are present in somatic cells as well as germ cells and suggesting a general and essential function for spheres in all nuclei. PMID- 8349729 TI - A cytosolic complex of p62 and rab6 associates with TGN38/41 and is involved in budding of exocytic vesicles from the trans-Golgi network. AB - TGN38/41, an integral membrane protein predominantly localized to the trans-Golgi network, has been shown to cycle to the plasma membrane and return to the TGN within 30 min. (Ladinsky, M. S., and K. E. Howell. 1992. Eur. J. Cell Biol. 59:92 105). In characterizing the proteins which associate with TGN38/41, a peripheral 62-kD protein, two forms of rab6 and two other small GTP-binding proteins were identified by coimmunoprecipitation. However, approximately 90% of the 62-kD protein is cytosolic and is associated with the same subset of small GTP-binding proteins. Both the membrane and cytoplasmic complexes were characterized by sizing column fractionation and velocity sedimentation. The membrane complex was approximately 250 kD (11.6 S) consisting of the cytosolic complex and a heterodimer of TGN38/41 (160 kD). The cytosolic complex was approximately 86 kD (6.1 S) consisting of p62 and one small GTP-binding protein. Preliminary evidence indicates that phosphorylation of the p62 molecule regulates the dissociation of the cytosolic complex from TGN38/41. Functionally the cytosolic p62 complex must bind to TGN38/41 for the budding of exocytic transport vesicles from the TGN as assayed in a cell-free system (Salamero, J., E. S. Sztul, and K. E. Howell. 1990. Proc. Natl. Acad. Sci. USA. 87:7717-7721). Interference with p62, rab6 or TGN38, and TGN41 cytoplasmic domains by immunodepletion or competing peptides completely inhibited the budding of exocytic transport vesicles. These results support an essential role for interaction of the cytosolic p62/rab6 complex with TGN38/41 in budding of exocytic vesicles from the TGN. PMID- 8349730 TI - Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. AB - GPI-linked protein molecules become Triton-insoluble during polarized sorting to the apical cell surface of epithelial cells. These insoluble complexes, enriched in cholesterol, glycolipids, and GPI-linked proteins, have been isolated by flotation on sucrose density gradients and are thought to contain the putative GPI-sorting machinery. As the cellular origin and molecular protein components of this complex remain unknown, we have begun to characterize these low-density insoluble complexes isolated from MDCK cells. We find that these complexes, which represent 0.4-0.8% of the plasma membrane, ultrastructurally resemble caveolae and are over 150-fold enriched in a model GPI-anchored protein and caveolin, a caveolar marker protein. However, they exclude many other plasma membrane associated molecules and organelle-specific marker enzymes, suggesting that they represent microdomains of the plasma membrane. In addition to caveolin, these insoluble complexes contain a subset of hydrophobic plasma membrane proteins and cytoplasmically-oriented signaling molecules, including: (a) GTP-binding proteins -both small and heterotrimeric; (b) annex II--an apical calcium-regulated phospholipid binding protein with a demonstrated role in exocytic fusion events; (c) c-Yes--an apically localized member of the Src family of non-receptor type protein-tyrosine kinases; and (d) an unidentified serine-kinase activity. As we demonstrate that caveolin is both a transmembrane molecule and a major phospho acceptor component of these complexes, we propose that caveolin could function as a transmembrane adaptor molecule that couples luminal GPI-linked proteins with cytoplasmically oriented signaling molecules during GPI-membrane trafficking or GPI-mediated signal transduction events. In addition, our results have implications for understanding v-Src transformation and the actions of cholera and pertussis toxins on hetero-trimeric G proteins. PMID- 8349732 TI - Beta and gamma actin mRNAs are differentially located within myoblasts. AB - Actin is of fundamental importance to all eukaryotic cells. Of the six mammalian actins, beta (beta) and gamma (gamma) cytoplasmic are the isoforms found in all nonmuscle cells and differ by only four amino acids at the amino-terminal region. Both genes are regulated temporally and spatially, though no differences in protein function have been described. Using fluorescent double in situ hybridization we describe the simultaneous intracellular localization of both beta and gamma actin mRNA. This study shows that myoblasts differentially segregate the beta and gamma actin mRNAs. The distribution of gamma actin mRNA, only to perinuclear and nearby cytoplasm, suggests a distribution based on diffusion or restriction to nearby cytoplasm. The distribution of beta actin mRNA, perinuclear and at the cell periphery, implicates a peripheral localizing signal which is unique to the beta isoform. The peripheral beta actin mRNA corresponded to cellular morphologies, extending processes, and ruffling edges that reflect cell movement. Total actin and gamma actin protein steady-state distributions were identified by specific antibodies. gamma actin protein was found in both stress fibers and at the cell plasma membrane and does not correspond to its mRNA distribution. We suggest that localized protein synthesis rather than steady-state distribution functionally differentiates between the actin isoforms. PMID- 8349731 TI - A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. AB - The dystrophin-glycoprotein complex was tested for interaction with several components of the extracellular matrix as well as actin. The 156-kD dystrophin associated glycoprotein (156-kD dystroglycan) specifically bound laminin in a calcium-dependent manner and was inhibited by NaCl (IC50 = 250 mM) but was not affected by 1,000-fold (wt/wt) excesses of lactose, IKVAV, or YIGSR peptides. Laminin binding was inhibited by heparin (IC50 = 100 micrograms/ml), suggesting that one of the heparin-binding domains of laminin is involved in binding dystroglycan while negatively charged oligosaccharide moieties on dystroglycan were found to be necessary for its laminin-binding activity. No interaction between any component of the dystrophin-glycoprotein complex and fibronectin, collagen I, collagen IV, entactin, or heparan sulfate proteoglycan was detected by 125I-protein overlay and/or extracellular matrix protein-Sepharose precipitation. In addition, laminin-Sepharose quantitatively precipitated purified dystrophin-glycoprotein complex, demonstrating that the laminin-binding site is accessible when dystroglycan is associated with the complex. Dystroglycan of nonmuscle tissues also bound laminin. However, the other proteins of the striated muscle dystrophin-glycoprotein complex appear to be absent, antigenically dissimilar or less tightly associated with dystroglycan in nonmuscle tissues. Finally, we show that the dystrophin-glycoprotein complex cosediments with F-actin but does not bind calcium or calmodulin. Our results support a role for the striated muscle dystrophin-glycoprotein complex in linking the actin-based cytoskeleton with the extracellular matrix. Furthermore, our results suggest that dystrophin and dystroglycan may play substantially different functional roles in nonmuscle tissues. PMID- 8349733 TI - Moving and stationary actin filaments are involved in spreading of postmitotic PtK2 cells. AB - We have investigated spreading of postmitotic PtK2 cells and the behavior of actin filaments in this system by time-lapse microscopy and photoactivation of fluorescence. During mitosis PtK2 cells round up and at cytokinesis the daughter cells spread back to regain their interphase morphology. Normal spreading edges are quite homogenous and are not comprised of two distinct areas (lamellae and lamellipodia) as found in moving edges of interphase motile cells. Spreading edges are connected to a network of long, thin, actin-rich fibers called retraction fibers. A role for retraction fibers in spreading was tested by mechanical disruption of fibers ahead of a spreading edge. Spreading is inhibited over the region of disruption, but not over neighboring intact fibers. Using photoactivation of fluorescence to mark actin filaments, we have determined that the majority of actin filaments move forward in spreading edges at the same rate as the edge. As far as we are aware, this is the first time that forward movement of a cell edge has been correlated with forward movement of actin filaments. In contrast, actin filaments in retraction fibers remain stationary with respect to the substrate. Thus there are at least two dynamic populations of actin polymer in spreading postmitotic cells. This is supported by the observation that actin filaments in some spreading edges not only move forward, but also separate into two fractions or broaden with time. A small fraction of postmitotic cells have a spreading edge with a distinct lamellipodium. In these edges, marked actin polymer fluxes backward with respect to substrate. We suggest that forward movement of actin filaments may participate in generating force for spreading in postmitotic cells and perhaps more generally for cell locomotion. PMID- 8349734 TI - Myosin and paramyosin of Caenorhabditis elegans embryos assemble into nascent structures distinct from thick filaments and multi-filament assemblages. AB - The organization of myosin heavy chains (mhc) A and B and paramyosin (pm) which are the major proteins of thick filaments in adult wild-type Caenorhabditis elegans were studied during embryonic development. As a probe of myosin paramyosin interaction, the unc-15 mutation e73 which produces a glu342lys charge change in pm and leads to the formation of large paracrystalline multi-filament assemblages was compared to wild type. These three proteins colocalized in wild type embryos from 300 to 550 min of development after first cleavage at 20 degrees C on the basis of immunofluorescence microscopy using specific monoclonal antibodies. Linear structures which were diversely oriented around the muscle cell peripheries appeared at 360 min and became progressively more aligned parallel to the embryonic long axis until distinct myofibrils were formed at 550 min. In the mutant, mhc A and pm were colocalized in the linear structures, but became progressively separated until they showed no spatial overlap at the myofibril stage. These results indicate that the linear structures represent nascent assemblies containing myosin and pm in which the proteins interact differently than in wild-type thick filaments of myofibrils. In e73, these nascent structures were distinct from the multi-filament assemblages. The overlapping of actin and mhc A in the nascent linear structures suggests their possible structural and functional relationship to the "stress fiber-like structures" of cultured vertebrate muscle cells. PMID- 8349735 TI - Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism. AB - Most models of mitotic congression and segregation assume that only poleward pulling forces occur at kinetochores. However, there are reports for several different cell types that both mono-oriented and bi-oriented chromosomes oscillate toward and away from the pole throughout mitosis. We used new methods of high resolution video microscopy and computer-assisted tracking techniques to measure the positions over time of individual kinetochores with respect to their poles during mitosis in living newt lung cells. The results show that kinetochores oscillate throughout mitosis when they are tethered to spindle poles by attachment to the plus-ends of kinetochore microtubules (kMTs). Oscillations were not sinusoidal. Instead, kinetochores abruptly (as quick as 6 s or less) switched between persistent (approximately 1.5 min average duration) phases of poleward (P) and away from the pole (AP) movement. This kinetochore "directional instability" was a property of motility at the plus-ends of kMTs since fluorescent marks on the lattice of kMTs have previously been observed to exhibit only relatively slow P movement. Each P and AP phase consisted of one or a few constant velocity domains (approximately 1.7 microns/min average velocity). Velocities of P and AP phases were similar from prometaphase through mid anaphase. Kinetochores occasionally switched to an indeterminant (N) phase of no or confused motion, which was usually brief compared to the durations of P and AP phases. Net chromosome displacements that occurred during congression to the equator or poleward movement during anaphase were primarily generated by differences in the durations and not the velocities of P and AP movements. Careful analysis of centromere deformation showed that kinetochore P movement produced pulling forces while kinetochore AP movement produced pushing forces. These data show that kinetochore directional instability is fundamental to the processes of chromosome congression and segregation. We argue that tension at the kinetochore attachment site is a key factor which controls the switching between P and AP phases of kinetochore motion. PMID- 8349736 TI - Phosphorylation of nuclear and flagellar basal apparatus proteins during flagellar regeneration in Chlamydomonas reinhardtii. AB - The antiphosphoprotein monoclonal antibody MPM-2 was used to investigate protein phosphorylation during flagellar regeneration in Chlamydomonas reinhardtii. MPM-2 recognizes a phosphorylated epitope and detects several Chlamydomonas proteins by Western immunoblot analysis. Two MPM-2 reactive proteins (34 and 90 kD) increase in Western immunoblot intensity after flagellar excision and decrease in intensity during flagellar regeneration. Immunofluorescence and immunogold labeling revealed MPM-2 staining within the nucleus, especially towards the nuclear periphery, the flagellar basal apparatus, and the nucleus-basal body connector after flagellar excision. Comparison of MPM-2 reactivity in wild-type cells and in the mutant bald-2, which lacks functional basal bodies, demonstrates that the 34-kD protein is localized in the nucleus and the 90-kD protein is localized in the flagellar basal region. MPM-2 reactivity is observed in cells competent for flagellar regeneration. However, when cells were treated with the kinase inhibitor, staurosporine, MPM-2 reactivity did not increase after flagellar excision and flagellar regeneration was impaired. These observations suggest that phosphorylation of the 34- and 90-kD proteins may be important for flagellar regrowth. Possible roles for phosphorylation in flagellar regeneration include transcriptional activation and transport of flagellar precursors to the base of the growing flagella. PMID- 8349737 TI - Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. AB - Hematopoietic stem cells (HSCs) are characterized by their ability to differentiate into all hematopoietic cell lineages while retaining their capacity for self renewal. One of the predictions of this model is the existence of a heterogeneous pool of HSCs, some members of which are destined to become lineage restricted progenitor cells while others function to renew the stem cell pool. To test whether HSCs are heterogeneous with respect to cell cycle status, we determined the fraction of phenotypically defined murine HSCs (Thy1.1lo Lin-/lo Sca-1+) that contain > 2n amount of DNA as measured by propidium iodide staining, Hoechst dye uptake and [3H]thymidine labeling; that fraction is 18-22%. In contrast, in the developing fetal liver, 40% of HSCs are in the S/G2/M phases of the cell cycle. Those HSCs which exhibit a low level of staining with rhodamine 123 are almost exclusively in G0/G1 (97%) whereas only 70% of HSCs which stain brightly for rhodamine 123 are in G0/G1. The injection of 100 G0/G1 HSCs rescued 90% of lethally irradiated mice in contrast to 100 S/G2/M HSCs, which protected only 25% of lethally irradiated recipients. Enhanced long-term donor-derived multilineage reconstitution of the peripheral blood was observed in recipients of 100 G0/G1 HSCs compared to recipients of 100 S/G2/M cells. These data indicate that a significant proportion of HSCs are actively proliferating during steady state hematopoiesis and that this subpopulation of cells exhibits reduced stem cell activity. PMID- 8349739 TI - Heparin-binding EGF-like growth factor stimulation of smooth muscle cell migration: dependence on interactions with cell surface heparan sulfate. AB - Heparin-binding EGF-like growth factor (HB-EGF), but not EGF, binds to cell surface heparan sulfate proteoglycan (HSPG). This was demonstrated in (a) the binding of 125I-HB-EGF to mutant CHO cells deficient in HS production was diminished by 70% compared to wild-type CHO cells, (b) the binding of 125I-HB-EGF to CHO cells and bovine aortic smooth muscle cells (BASMC) was diminished 80% by heparitinase or chlorate treatment, and (c) 125I-EGF did not bind to CHO cells and its binding to BASMC was not diminished at all by heparitinase and only slightly by chlorate treatment. Accordingly, the role of HB-EGF interactions with HSPG in modulating bioactivity was examined. Heparitinase or chlorate treatment of BASMC diminished the ability of HB-EGF to stimulate BASMC migration by 60-80%. A similar inhibition of migration occurred when BASMC were treated with a synthetic peptide (P21) corresponding to the sequence of the putative heparin binding domain of HB-EGF. As a control for BASMC viability, and for specificity, it was found that heparitinase and P21 did not inhibit at all and chlorate inhibited only slightly the stimulation of BASMC migration by PDGF AB. Since heparitinase, chlorate, and P21 treatment also diminished by 70-80% the cross linking of 125I-HB-EGF to the EGF receptor, it was concluded that the interaction of HB-EGF, via its heparin-binding domain, with cell surface HSPG was essential for its optimal binding to the EGF receptor on BASMC and hence for its optimal ability to stimulate migration. PMID- 8349738 TI - Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism. AB - Thrombospondin (TSP) forms specific complexes with transforming growth factor beta (TGF-beta) in the alpha granule releasate of platelets and these TSP-TGF beta complexes inhibit the growth of bovine aortic endothelial cells (BAE). In these studies, we report that TSP stripped of associated TGF-beta (sTSP) retained growth inhibitory activity which was partially reversed by a neutralizing antibody specific for TGF-beta. Since BAE cells secrete latent TGF-beta, we determined whether sTSP activates the latent TGF-beta secreted by BAE cells. Cells were cultured with or without sTSP and then the conditioned medium was tested for the ability to support TGF-beta-dependent normal rat kidney (NRK) colony formation in soft agar. Medium conditioned with sTSP showed a dose- and time-dependent ability to stimulate BAE-secreted TGF-beta activity, reaching maximal activation by 1-2 h with 0.4 micrograms/ml (0.9 nM) sTSP. The sTSP mediated stimulation of TGF-beta activity is not dependent on serum factors and is not a general property of extracellular matrix molecules. The sTSP-mediated stimulation of TGF-beta activity was blocked by a mAb specific for sTSP and by neutralizing antibodies to TGF-beta. Activation of BAE cell secreted latent TGF beta by sTSP can occur in the absence of cells and apparently does not require interactions with cell surface molecules, since in conditioned medium removed from cells and then incubated with sTSP, activation occurs with kinetics and at levels similar to what is seen when sTSP is incubated in the presence of cells. Serine proteases such as plasmin are not involved in sTSP-mediated activation of TGF-beta. Factors that regulate the conversion of latent to active TGF-beta are keys to controlling TGF-beta activity. These data suggest that TSP is a potent physiologic regulator of TGF-beta activation. PMID- 8349741 TI - Shape-selective separation of polycyclic aromatic hydrocarbons by reversed-phase liquid chromatography on tetraphenylporphyrin-based stationary phases. AB - The reversed-phase chromatographic behavior of planar and non-planar polycyclic aromatic hydrocarbons (PAHs) is investigated on tetraphenylporphyrin and two metallotetraphenylporphyrin [Sn(IV), In(III)] bonded stationary phases using methanol-water and acetonitrile-water as mixed solvent mobile phases. Large differences in the capacity factors of aromatic solute pairs having the same number of carbon atoms, but differing in three-dimensional shape (e.g., triphenylene/o-terphenyl and perylene/alpha, alpha'-binaphthyl), suggest that the three tetraphenylporphyrin-based supports possess shape selectivity toward small planar aromatic solutes. Capacity factors for planar PAH solutes on these supports are significantly greater than for non-planar polyaryls having the same number of carbon atoms. PMID- 8349740 TI - Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds. AB - Both carcinoembryonic antigen (CEA) and neural cell adhesion molecule (NCAM) belong to the immunoglobulin supergene family and have been demonstrated to function as homotypic Ca(++)-independent intercellular adhesion molecules. CEA and NCAM cannot associate heterotypically indicating that they have different binding specificities. To define the domains of CEA involved in homotypic interaction, hybrid cDNAs consisting of various domains from CEA and NCAM were constructed and were transfected into a CHO-derived cell line; stable transfectant clones showing cell surface expression of CEA/NCAM chimeric-proteins were assessed for their adhesive properties by homotypic and heterotypic aggregation assays. The results indicate that all five of the Ig(C)-like domains of NCAM are required for intercellular adhesion while the COOH-terminal domain containing the fibronectin-like repeats is dispensable. The results also show that adhesion mediated by CEA involves binding between the Ig(V)-like amino terminal domain and one of the Ig(C)-like internal repeat domains: thus while transfectants expressing constructs containing either the N domain or the internal domains alone were incapable of homotypic adhesion, they formed heterotypic aggregates when mixed. Furthermore, peptides consisting of both the N domain and the third internal repeat domain of CEA blocked CEA-mediated cell aggregation, thus providing direct evidence for the involvement of the two domains in adhesion. We therefore propose a novel model for interactions between immunoglobulin supergene family members in which especially strong binding is effected by double reciprocal interactions between the V-like domains and C-like domains of antiparallel CEA molecules on apposing cell surfaces. PMID- 8349742 TI - An efficient preparative chromatographic method for the separation and purification of low molecular weight naphthalenesulfonic acid mixtures. AB - These studies describe an efficient preparative method of separating and purifying polar mixtures of low molecular weight (mol wt) sulfonic acid derivatives containing one to six sulfonic acid moieties and possessing mol wt differences ranging from less than 100 and up to 650. This gel permeation chromatography procedure successfully separates materials with similar charges, requires no prepurification step, uses inexpensive apparatus, and employs water as the eluant. This technique has quantitative recovery and is potentially applicable to other anionic separations. PMID- 8349743 TI - Unrelatedness of groups of yeasts within the Candida haemulonii complex. AB - Isoenzyme and protein profiles of clinical isolates initially identified as Candida haemulonii demonstrated the presence of two distinct groups. DNA relatedness studies with representative cultures confirmed the presence of two species. Physiological features that can be used to separate two groups within C. haemulonii are reported. PMID- 8349744 TI - Direct detection of Mycobacterium tuberculosis in respiratory specimens in a clinical laboratory by polymerase chain reaction. AB - The emergence of epidemic multiple-drug-resistant (MDR) strains of Mycobacterium tuberculosis in conjunction with an increase in the number of reported cases of tuberculosis (TB) represents a major public health problem. In light of a recent outbreak of MDR M. tuberculosis at our center, we began the development of a polymerase chain reaction (PCR) assay for the rapid diagnosis of pulmonary TB using two sets of primers, one based on the IS6110 repeated sequence of M. tuberculosis and the other based on the protein antigen b (PAB). Reaction conditions were first optimized as to the appropriate extraction protocol and the concentrations of primer pairs, nucleotides, and MgCl2. Following a preliminary evaluation of the assay with clinical specimens, extraction and amplification procedures were further modified. PAB and IS6110 primers detected between 2 and 23 and 0.023 and 0.23 CFU of M. tuberculosis, respectively, in pooled, M. tuberculosis-negative sputa by our optimized PCR assay. After routine processing for mycobacteria, 734 specimens were subsequently amplified. DNA for amplification was obtained by boiling and beating the sediments with Tween 20. For each reaction, DNA (10 microliters) was added to an amplification mixture containing 12 pmol of IS6110 primers, 20 pmol of PAB primers, 2 mM MgCl2, 200 microM nucleotides, and 2.5 U of Taq polymerase and the mixture was then amplified for 40 cycles. The sensitivity and specificity of our PCR assay were 87.2 and 97.7%, respectively. We were unable to interpret the results for seven specimens (1%). In our experience, PCR proved to be a useful rapid diagnostic test for TB in a clinical setting and a valuable epidemiological tool for determining exposure groups in the hospital setting. Our findings also underscore the need for the systematic optimization of PCR assay conditions. PMID- 8349745 TI - Ability of clinical laboratories to detect antimicrobial agent-resistant enterococci. AB - To test the ability of clinical laboratories to detect antimicrobial resistance among enterococci, we sent four vancomycin-resistant enterococcal strains and one beta-lactamase-producing enterococcus to all 93 nongovernment, hospital-based clinical laboratories in New Jersey; 76 (82%) participated in the study. Each organism was tested by the laboratory's routine antimicrobial susceptibility testing method. The proportion of laboratories that correctly reported that an isolate was resistant to vancomycin varied according to the resistance level of the isolate: high-level resistance (MIC for Enterococcus faecium = 512 micrograms/ml), 96% of laboratories correct; moderate-level resistance (MIC for E. faecium = 64 micrograms/ml), 27% correct; low-level resistance (MIC for Enterococcus faecalis = 32 micrograms/ml), 16% correct; and intrinsic low-level resistance (MIC for Enterococcus gallinarum = 8 micrograms/ml), 74% correct. The beta-lactamase-producing E. faecalis isolate was identified as resistant to penicillin and ampicillin by 66 and 8% of laboratories, respectively, but only three laboratories recognized that it was a beta-lactamase producer. This survey suggests that many laboratories may fail to detect antimicrobial agent-resistant enterococci. PMID- 8349746 TI - Application of indirect immunofluorescence to detection of Dientamoeba fragilis trophozoites in fecal specimens. AB - An indirect fluorescent-antibody (IFA) assay was carried out to examine for the presence of Dientamoeba fragilis trophozoites in preserved fecal specimens. Antiserum to D. fragilis trophozoites was raised in a rabbit with a dixenic culture of D. fragilis (ATCC 30948) from the American Type Culture Collection. After absorption with Klebsiella pneumoniae and Bacteroides vulgatus, the immune rabbit serum was used for examination by the IFA assay. A total of 155 clinical samples were tested; 42 with no parasites, 9 with D. fragilis, and 104 with other parasites. The IFA assay identified seven D. fragilis organisms. Two specimens with doubtful IFA assay readings showed very scanty amounts of D. fragilis trophozoites on stained smears. There were no false-positive IFA assay readings. The IFA assay appeared to be a promising method because of its speed in screening. The specificity of the IFA assay indicates that other diagnostic tests such as an enzyme-linked immunosorbent assay could be developed to identify D. fragilis antigens in fecal specimens. PMID- 8349748 TI - Virulence-associated plasmids in Rhodococcus equi. AB - Twenty-three strains of Rhodococcus equi from independent clinical cases were analyzed for the presence of virulence plasmid DNA. Of the clinical isolates, 19 contained an 85-kb plasmid and the remaining 4 contained a 90-kb plasmid. All of the isolates expressed 15- to 17-kDa antigens and were virulent in mice. Restriction enzyme and Southern blot analyses showed large regions of DNA homology between the 85- and 90-kb virulence plasmids. It was concluded tentatively that there are at least two virulence plasmids in R. equi and that they have a common origin. PMID- 8349747 TI - Major outbreak of pertussis in northern Alberta, Canada: analysis of discrepant direct fluorescent-antibody and culture results by using polymerase chain reaction methodology. AB - A major outbreak of 5,683 cases of pertussis occurred in northern Alberta, Canada, from December 1989 to January 1991. The outbreak highlighted a number of problems with current methods of pertussis diagnosis. In particular, an exceptionally high proportion of direct fluorescent-antibody (DFA)-positive, culture-negative specimens (88.4%) was identified. We took this opportunity to use polymerase chain reaction (PCR) methodology to examine whether the low culture rates were due to specimens containing dead organisms or whether the DFA results represented high numbers of false-positive results. A set of primer sequences within a Bordetella pertussis-specific repetitive element was used to amplify proteinase K extracts of B. pertussis DNA recovered from 279 submitted slides inoculated at the point of collection with nasopharyngeal material obtained from pernasal swabs. The PCR data corroborated the culture results: 84.6% of DFA-positive, culture-negative specimens were similarly PCR negative. At least three different bacterial species that were significantly cross-reactive with the commercial DFA reagent were identified in clinical specimens and in pure culture, providing one possible explanation for the false-positive DFA results. These results and other limitations of current diagnostic techniques underline the urgent need for a new DFA reagent with improved specificity and a standardized means of measuring the patient antibody response for the diagnosis of pertussis. PMID- 8349749 TI - Preliminary evaluation of recombinant Onchocerca volvulus antigens for serodiagnosis of onchocerciasis. AB - Serodiagnostic assays for onchocerciasis based on native antigens are hampered by the scarcity of antigen, and they suffer from poor specificity. The present study was designed to evaluate the diagnostic utility of recently described recombinant Onchocerca volvulus antigens OC 3.6 and OC 9.3 in enzyme immunoassays. The recombinant proteins were expressed as glutathione S-transferase fusions and were tested in several enzyme immunoassay formats to measure immunoglobulin G (IgG) and IgG4 antibodies with sera from patients with onchocerciasis in Nigeria and with various types of control sera. The best results were obtained by measuring IgG4 antibodies to the fusion proteins. Forty of 42 (95%) serum specimens from patients with onchocerciasis were reactive with OC 3.6; the reactivity with OC 9.3 was 81%. Results obtained with sera from experimentally infected chimpanzees suggest that OC 3.6 might be especially useful for detecting prepatent infections in humans, while OC 9.3 mainly detects mature, patent infections. Sera from individuals in Nigeria and the United States residing in areas nonendemic for onchocerciasis were uniformly nonreactive with these antigens in IgG and IgG4 assays, as were sera from patients with bancroftian filariasis, brugian filariasis, loiasis, ascariasis, schistomiasis, and dracunculiasis. These results suggest that enzyme immunoassays based on the recombinant antigens OC 3.6 and OC 9.3 are useful for the diagnosis of onchocerciasis. PMID- 8349750 TI - Characterization of two DNA probes specific for Serpulina hyodysenteriae. AB - Two DNA probes, one 1.1- and one 0.75-kb probe, specific for Serpulina hyodysenteriae were isolated from a genomic library generated from virulent S. hyodysenteriae 5380. These probes are highly specific and react with all S. hyodysenteriae strains tested. Under stringent conditions, the DNA probes did not react with the nonpathogenic species Serpulina innocens or with other species of enteric bacteria, including Escherichia coli. Both probes are able to detect S. hyodysenteriae in colony blot hybridizations, and when applied to fecal specimens, they can detect 10(4) S. hyodysenteriae cells in 0.1 g of seeded fecal matter. Both probes can detect S. hyodysenteriae in fecal specimens from swine with clinical signs of swine dysentery after experimental challenge and from swine from a herd with an acute outbreak of swine dysentery. These probes have application as a diagnostic tool in veterinary microbiology. PMID- 8349751 TI - Routine application of high-performance liquid chromatography for identification of mycobacteria. AB - Mycolic acid analysis by high-performance liquid chromatography (HPLC) was introduced in our laboratory as the routine technique for identifying all clinical isolates of mycobacteria referred to us. HPLC identified 96.1% of the 1,103 strains analyzed, whereas the biochemical procedures and/or the commercial DNA probes identified 98.3% of strains, for an overall agreement of 94.4%. Compared with the probes, there was 100% specificity and 98.9% sensitivity for Mycobacterium tuberculosis identification. HPLC allowed early detection and identification of the rare mycobacterial species M. haemophilum, M. malmoense, M. shimoidei, and M. fallax as well as uncharacteristic strains of M. simiae. After 18 months of routine use, HPLC proved to be reliable, easy to perform, rapid, and less costly than other identification methods. PMID- 8349752 TI - Diagnosis of Helicobacter pylori infection in adults and children by using the Malakit Helicobacter pylori, a commercially available enzyme-linked immunosorbent assay. AB - Malakit Helicobacter pylori (Biolab, Limal, Belgium) is a second-generation enzyme-linked immunosorbent assay (ELISA) for the detection of Helicobacter pylori infection. We evaluated its ability to diagnose H. pylori infection in 489 asymptomatic pregnant women, 427 asymptomatic children, and 95 symptomatic children. 87 asymptomatic adults (17.8%), 31 asymptomatic children (7.3%), and 27 symptomatic children (28.4%) were seropositive. We observed an increase in H. pylori infection with age. 13C-urea breath tests were performed for all seropositive and 100 randomly selected seronegative asymptomatic adults. They were also performed for all seropositive and 65 randomly chosen seronegative asymptomatic children. Breath tests were positive for 86 of 87 (98.9%) seropositive adults, 30 of 31 seropositive children (96.8%), and no seronegative individual. Compared with those of culture, the sensitivity and specificity of the Malakit Helicobacter pylori were both 96%. We conclude that the Malakit Helicobacter pylori is equally suitable for adults and children. Therefore, this ELISA can be proposed as an important alternative to other more time-consuming and/or more expensive diagnostic tests for the detection of H. pylori. PMID- 8349753 TI - Direct detection of Mycobacterium tuberculosis in sputum by polymerase chain reaction and DNA hybridization. AB - A polymerase chain reaction (PCR) assay for the rapid diagnosis of pulmonary tuberculosis was developed by using oligonucleotide primers to amplify a fragment of IS6110, an insertion sequence repeated multiple times in the chromosome of Mycobacterium tuberculosis. Sediment obtained from sputa processed by the N acetyl-L-cysteine-NaOH method was suspended in a simple lysis buffer and was heated at 100 degrees C for 30 min prior to amplification. A dUTP-uracil N glycosylase PCR protocol was used to prevent false-positive test results because of the carryover of products from previous amplification reactions. The 317-bp amplicon was detected by direct gel analysis and Southern blotting and then hybridization with a biotin-labeled internal probe. Hybrid molecules were detected by using a commercially available avidin-alkaline phosphatase chemiluminescent substrate system (Tropix, Inc., Bedford, Mass.). The analytical sensitivity of the assay was 10 fg of purified mycobacterial DNA. The limits of detection by culture (Middlebrook 7H11 agar and Lowenstein-Jensen medium) and by PCR were equivalent in terminal dilution experiments for organism suspensions and positive sputa. An internal control was used to detect the presence of amplification inhibitors in each negative reaction mixture. DNA was purified from inhibitory specimens by phenol-chloroform extraction and ethanol precipitation. PCR results were compared with results of microscopy and conventional culture for the detection of M. tuberculosis in 313 sputum specimens. There were 124 specimens that were positive for M. tuberculosis by conventional methods and 113 (91%) that were positive by PCR. PCR detected 105 of 110 (95%) of the smear positive and 8 of 14 (57%) of the smear-negative specimens. There were no false positive results by PCR (specificity, 100%). This PCR assay innovations that make application of this new technology feasible in clinical microbiology laboratories. PMID- 8349754 TI - Evidence of multiple taxa within commercially available reference strains of Corynebacterium xerosis. AB - Attempts to identify coryneform isolates resembling Corynebacterium xerosis can lead clinical microbiologists to identification schemes with conflicting descriptions which result in confusing C. xerosis with Corynebacterium striatum. For the present study we purchased all available American Type Culture Collection and National Collection of Type Cultures reference cultures of C. xerosis (n = 10) and C. striatum (n = 4) and analyzed them as follows: (i) analysis of biochemical reactions in conventional tests and in the Rapid CORYNE system, (ii) whole-cell fatty acid analysis by using the gas-liquid chromatography research software of Microbial ID, Inc., and (iii) analysis of DNA homology in dot blot hybridizations. Three C. xerosis strains were indistinguishable from the C. striatum strains in whole-cell fatty acid analyses and DNA hybridizations and shared very similar biochemical reactions. The remaining seven strains of C. xerosis clustered into five groups on the basis of fatty acid patterns, DNA hybridizations, and biochemical tests. No reference strain of C. striatum fit the species description in Bergey's Manual of Systematic Bacteriology. The type strains of both C. striatum and C. xerosis fit their respective descriptions by the Centers for Disease Control and Prevention. This study suggests that the 10 commercially available reference strains of C. xerosis represent six different taxa which should be assigned to new species. PMID- 8349755 TI - Reproducibility of lysis-centrifugation cultures for quantification of Mycobacterium avium complex bacteremia. AB - While quantitative mycobacterial blood cultures have been accepted as the standard for evaluating response to various Mycobacterium avium complex (MAC) treatment regimens, variability in this methodology has not been evaluated in a rigorous fashion. We thus studied the reproducibility of quantitative MAC cultures by a lysis-centrifugation culture system within and among five institutions. To measure the intralaboratory variation in mycobacterial colony counts, colony counts from duplicate blood specimens collected from 52 AIDS patients with MAC bacteremia were determined. Colony counts ranged from 0 to 50,000 CFU/ml. Nonparametric analyses revealed there was no significant difference in colony counts between the 52 duplicate specimens. The agreement between the intralaboratory paired specimens, as measured by the intraclass correlation coefficient, was 0.997. To measure the interlaboratory variation, multiple 10-ml aliquots from 12 patients were distributed to five institutions and processed within 24 to 32 h by lysis-centrifugation. For the 12 specimens distributed to the five laboratories, two-way analysis of variance for repeated measures revealed no significant difference in an individual patient's colony counts between laboratories (P > 0.2). We conclude that quantitation of mycobacterial colony counts by the lysis-centrifugation system is reproducible within and between institutions. Clinical trials evaluating response to therapeutic interventions for MAC can use multiple laboratories for quantitation of mycobacteremia. Furthermore, a 24- to 32-h delay in processing appeared to have no impact on reproducibility. PMID- 8349756 TI - Effects of fixation and varying target length on the sensitivity of polymerase chain reaction for detection of human T-cell leukemia virus type I proviral DNA in formalin-fixed tissue sections. AB - In this study, the fixation condition most suitable for maintaining the sensitivity of the polymerase chain reaction (PCR) was investigated by using the alpha-tubulin gene sequence, and the PCR procedure most effective for detecting human T-cell leukemia virus type I (HTLV-I) proviral sequences in fixed, embedded tissues of adult T-cell leukemia patients was explored. First, the sensitivity of the PCR targeting a 286-bp alpha-tubulin sequence was studied in tissue sections fixed in several fixatives for various periods at 25 or 4 degrees C. For histological examination, fixation with 10% buffered formalin at a lower temperature for a shorter period was found to be preferable to retain the sensitivity. And the HTLV-I sequence was detected in only 7 of 18 specimens (38.9%) when the 374-bp sequence of the gag region was targeted, but the rate increased to 77.8% (14 of 18 specimens) when the length of the target sequence was reduced to 120 bp within the same region. Therefore, the one-round PCR targeting a shorter sequence is preferable for application of PCR to archival fixed tissue specimens, the fixation condition of which may not be ideal for DNA preservation. PMID- 8349757 TI - A phaeohyphomycotic cyst and peritonitis caused by Phialemonium species and a reevaluation of its taxonomy. AB - Two cases of human fungal infections caused by members of the genus Phialemonium, a genus proposed by Gams and McGinnis (1983) for fungi intermediate between the genera Acremonium and Phialophora, are presented. The first case was a phaeohyphomycotic cyst on the foot of a renal transplant recipient. The fungus was detected by direct examination and histopathology and was recovered by several procedures over 4 months. It was flat, glabrous, and white becoming yellow with the production of a diffusible yellow pigment; it had conidiophores that were mostly solitary and lateral and terminal phialides and adelophialides with distinct collarettes producing cylindrical to curved conidia. The isolate resembled both Phialemonium dimorphosporum and Phialemonium curvatum, although its characteristics were more consistent with those of the latter. The second case was peritonitis in a renal transplant recipient. The fungus was white-to cream colored and yeast like, but later became black with a green diffusible pigment, and produced obovoid conidia; it was easily identified as Phialemonium obovatum. Difficulties encountered in the identification and taxonomy of members of this genus highlight the need for standardized conditions, e.g., potato dextrose agar culture incubated at 24 to 25 degrees C for morphologic comparisons, to control significant variations due to culture conditions. PMID- 8349758 TI - Diagnosis of Mycobacterium avium bacteremia by polymerase chain reaction. AB - We describe a rapid polymerase chain reaction (PCR)-based test for diagnosing Mycobacterium avium directly from blood specimens. Blood was collected in anticoagulant (EDTA) from patients who also had blood cultures performed by the lysis-centrifugation method. Blood samples were centrifuged on a Ficoll-Hypaque gradient to purify peripheral blood mononuclear cells. The purified cells were washed and incubated in the presence of Chelex-100 (a divalent cation-binding resin), boiled to release mycobacterial DNA, and then amplified with M. avium specific PCR primers. Amplification was detected by hybridization with radiolabelled probe, and the results were compared with the culture results. The PCR assay gave positive results for 12 of 15 specimens that were taken from patients with positive cultures for M. avium complex (sensitivity, 80%). The three PCR-negative specimens in this group showed evidence of PCR inhibition. The PCR assay gave positive results for 32 of 228 specimens taken from patients with negative cultures (specificity, 86%). Of these 32 PCR-positive culture-negative specimens, 27 were also positive when amplified with primers specific for the genus Mycobacterium, suggesting that PCR may be more sensitive than culture. PMID- 8349759 TI - Antigen detection and immunological typing of Haemophilus ducreyi with a specific rabbit polyclonal serum. AB - A rabbit polyclonal serum was raised against the 29-kDa species-specific marker, as well as the 30- to 34-kDa immunotype-specific markers of Haemophilus ducreyi described elsewhere (E. Roggen, S. De Breucker, E. Van Dyck, and P. Piot, Infect. Immun. 60:590-595, 1992). These antigens were purified from a cocktail of H. ducreyi isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The immune serum reacted in enzyme-linked immunosorbent assay (ELISA) preferentially with H. ducreyi, at a titer as high as 50,000. To make it specific to H. ducreyi, nonspecific antibodies were removed by adsorption on a mixture of Haemophilus spp., Escherichia coli, Candida albicans, and Corynebacterium spp. In the 29- to 34-kDa region of immunoblot profiles from H. ducreyi isolates (n = 450), the adsorbed serum revealed essentially the same antigens as did a pool of well-characterized human sera. Yet, eight different immunotypes were observed. With this rabbit polyclonal serum, an ELISA-based antigen detection test was developed. The adsorbed serum reacted specifically with all H. ducreyi isolates tested (n = 450), but not with other bacterial species (n = 15). This test was evaluated with a limited number of clinical specimens from African patients with culture-proven chancroid and no evidence for any other ulcerating etiology (n = 10) and a number of chancroid-negative control patients from Belgium (n = 20). Within this context, the test yielded a sensitivity and specificity of 100%. PMID- 8349760 TI - Growth and survival of Serratia marcescens under aerobic and anaerobic conditions in the presence of materials from blood bags. AB - Several patients receiving blood transfusions during the summer of 1991 developed bacteremia after the transfusion. In all cases, the infection was caused by Serratia marcescens. The same strain of Serratia marcescens was isolated from the patients and from the outer surface of unfilled blood bags. The transport containers for the blood bags were made anoxic by using a catalyst in order to prevent microbial growth. The survival and growth of S. marcescens K202, which was isolated from the blood bags, was studied at different oxygen concentrations in deionized water containing materials derived from the blood bags. The rate of survival and growth of S. marcescens was highest under anaerobic conditions, in which growth occurred with all materials and even in deionized water alone. In contrast, S. marcescens did not survive in control cultures under semi-anaerobic and aerobic conditions. Growth was observed, however, under both aerobic and semi anaerobic conditions in the presence of each of the tested blood bag materials. These findings indicate that the conditions in the transport containers for the blood bags were favorable for the survival and growth of S. marcescens. PMID- 8349761 TI - Identification and characterization of Lyme disease spirochetes, Borrelia burgdorferi sensu lato, isolated in Korea. AB - Lyme disease spirochetes, Borrelia burgdorferi sensu lato, were identified and characterized for the first time in Korea. Four isolates, designated Konkuk-1, Konkuk-2, Kangwon-3, and KM-4, were made from midgut suspensions of three Ixodes ticks and heart tissue from one mouse, Apodemus agrarius, collected from Chungbuk and Kangwon provinces. The four Korean isolates and B. burgdorferi sensu lato from other geographic areas and biological sources were compared by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis for protein profiles, Western blot (immunoblot) analysis for reactivities with monoclonal and polyclonal antibodies, and agarose gel electrophoresis for plasmid profiles. Two typing schemes using polymerase chain reaction identified three of the isolates as members of group VS461 and one, Kangwon-3, as Borrelia garinii. These results demonstrate the potential for human Lyme disease to occur in some provinces of Korea. PMID- 8349762 TI - Cloning of a DNA sequence unique to Clostridium botulinum group I by selective hybridization. AB - Nucleic acid sequences were isolated from a strain of Clostridium botulinum type A by a selective hybridization method known as deletion enrichment. Nontoxigenic C. sporogenes was used to produce a C. botulinum type A sequence-enriched library. A probe, pCBM44, which showed specific hybridization to a 4.0-kb HindIII fragment present in all of the C. botulinum type A strains tested was isolated, and there was no hybridization to any strains of C. sporogenes. Upon further investigation, pCBM44 was found to hybridize to all of the group I proteolytic C. botulinum strains tested (toxin types A, B, and F) but not to hybridize to groups II, III, and IV (toxin types B, C, D, or E). The probe did not cross-react with nine other Clostridium spp. Such a probe, which differentiates between nontoxigenic C. sporogenes and neurotoxigenic C. botulinum group I strains, should prove extremely useful. PMID- 8349763 TI - Bacteroides fragilis strains express multiple capsular polysaccharides. AB - Previous studies by our group have demonstrated that the capsule of Bacteroides fragilis type strain NCTC 9343 consists of two chemically distinct polysaccharides, designated PS A and PS B. These polysaccharides can be isolated as an aggregate from the surface of the organism and give a complex multiprecipitin profile when they are reacted with homologous antiserum in an immunoelectrophoresis assay. Following structural analysis of PS A and PS B, we have determined that the complex precipitin profile is formed as a result of the differing electrophoretic and antigenic properties associated with each of these polymers. Presently, we have examined the capsular polysaccharides of 13 other strains of B. fragilis according to methods used for the prototype strain. The capsules of these strains were extracted, partially purified, and analyzed by immunoelectrophoresis at pH 7.3. Following reaction with homologous polyclonal antisera, each of the capsular preparations tested yielded a complex precipitin profile similar to that of the prototype strain. When reacted by immunoelectrophoresis with polyclonal antiserum to 9343 or with monoclonal antibodies to PS A and PS B, these capsular preparations appeared to be antigenically diverse; some preparations (50%) showed complete or partial cross reaction. These results suggest that the dual polysaccharide motif seen with the prototype strain is a common feature of B. fragilis strains. In addition, the antigenic heterogeneity of B. fragilis capsular polysaccharides could be used for the development of a serological typing scheme. PMID- 8349764 TI - Identification of Actinobacillus actinomycetemcomitans by leukotoxin gene specific hybridization and polymerase chain reaction assays. AB - Eleven strains of Actinobacillus actinomycetemcomitans isolated from cases of systemic infections, local abscesses, and periodontitis were identified by genetic assays using the leukotoxin gene as the target. We have developed a polymerase chain reaction (PCR) assay, based on the leukotoxin structural gene of this pathogen, which clearly identified all tested strains of A. actinomycetemcomitans and separated them from the closely related Haemophilus aphrophilus as well as other bacterial species. Furthermore, DNA-DNA hybridization was performed with the cloned partial leukotoxin structural gene (lktA) as a probe, which again clearly distinguished A. actinomycetemcomitans from H. aphrophilus, parts of the normal oral flora, and species harboring RTX (repeats in toxin) family-related cytotoxins. The PCR fragment amplified from the leukotoxin structural gene gave results similar to those given by the cloned leukotoxin gene when used as a probe in hybridization experiments. The hybridization and PCR assays described here are fundamental improvements for the identification of A. actinomycetemcomitans. PMID- 8349765 TI - Detection of Toxoplasma gondii in venous blood from AIDS patients by polymerase chain reaction. AB - Detection of Toxoplasma gondii in blood by means of the polymerase chain reaction (PCR) may facilitate the diagnosis and follow-up of cerebral toxoplasmosis in patients with AIDS. We evaluated this approach with seven patients with tissue culture-proven parasitemia, 14 patients with presumptive cerebral toxoplasmosis, and 17 healthy human immunodeficiency virus-positive controls. Each sample of blood was assayed on three different occasions by a PCR assay based on detection of the gene encoding the P30 surface protein. A positive PCR diagnosis required positivity in at least two of the three PCR tests. None of the controls had a positive PCR diagnosis, but six of the seven patients with parasitemia did. Cerebral toxoplasmosis was confirmed in 13 of the 14 patients with a presumptive diagnosis; diagnosis by PCR was positive before treatment for 9 of these 13 patients, whereas tissue culture was positive for only 1 patient. During treatment, blood samples were taken from 14 patients at regular intervals until day 12. PCR diagnosis became negative on ethidium-stained gels, but persistent signals were observed after hybridization, in some cases, for up to 12 days after initiation of therapy. PCR on venous blood could thus be a sensitive and noninvasive method for the diagnosis of cerebral and disseminated toxoplasmosis in AIDS patients and could be a potential tool for monitoring the effects of treatment. PMID- 8349766 TI - Curvilinear-gradient high-performance liquid chromatography for identification of mycobacteria. AB - Over a 1-year period, 502 mycobacterial cultures submitted to the Microbial Diseases Laboratory were identified by high-performance liquid chromatography (HPLC) in parallel with standard biochemical methods. Identification by HPLC using a curvilinear gradient was achieved by comparing the chromatograms of the unknown cultures to chromatograms for known reference strains, together with calculation of peak height or peak area ratios, as necessary. The overall agreement between HPLC and biochemical identification was 97.2%. In addition, 7 of 12 cultures of Mycobacterium bovis were identified by HPLC as the BCG strain. Of 111 cultures biochemically identified as members of the M. avium complex (MAC), 108 were confirmed as MAC by DNA probe and 106 were confirmed by HPLC. Of the latter 106, 58 probe-positive strains were identified as M. avium, 38 were identified as M. intracellulare, and 10 were identified as Mycobacterium sp. strain "X" by HPLC. Of the remaining five nonchromogenic cultures, four had MAC like chromatograms that did not match any in our library sufficiently to permit definitive identification. Of the latter four, two were confirmed as MAC strains by DNA probe and two were not. The last of the cultures biochemically identified as MAC (1 of 111) was a mixture of MAC and non-MAC strains. Overall, only 2 of 502 cultures yielded results by HPLC that differed from those obtained by standard biochemical methods. The HPLC result was confirmed in both cases by an independent national reference laboratory. In the 12 instances in which HPLC did not provide identification, the chromatograms were either uninterpretable or did not match available reference chromatograms. These findings show that the identification obtained by HPLC concurs well with that obtained by both the standard biochemical methods and the DNA probes. Thus, identification by HPLC provides mycobacteriology laboratories with a reproducible and specific method for accurate and timely identification of most medically important mycobacteria. PMID- 8349767 TI - Development and evaluation of a blood-free medium for determining growth curves and optimizing growth of Rochalimaea henselae. AB - Two strains of Rochalimaea henselae were used to optimize a blood-free growth medium. Seven agar bases, four broths, and combinations of eight supplements were evaluated. Acceptable growth was achieved in media containing Fildes solution and hemin, with the best growth demonstrated in brucella broth or on brucella agar with 6 to 8% Fildes solution and 250 micrograms of hemin per ml. R. henselae utilized hemin in concentrations six times that utilized by Rochalimaea quintana. Erythrocyte membrane was necessary to achieve the full growth-promoting effect of rabbit blood. PMID- 8349769 TI - Confirmation of positive results for chlamydial antigen by the Chlamydiazyme assay: value of repeated testing and a blocking antibody assay. AB - We studied the specificity of the Abbott Chlamydiazyme test for detection of Chlamydia trachomatis antigen by means of a specific blocking antibody test. A total of 457 previously positive specimens were tested; 22 did not block in the blocking antibody test, 39 did not repeat as positive, and 396 were confirmed as positive. The distribution of A492 values obtained with specimens which did not repeat as positive was nonrandom and was concentrated between the cutoff values and 0.400. The positive predictive value of the Chlamydiazyme assay after initial testing was 86.7% (396 of 457), but the positive predictive value increased to 94.7% (396 of 418) if specimens which were not repeatedly positive were considered negative. We recommend routinely repeating the Chlamydiazyme assay for all specimens which give A492 values between the cutoff and 0.400 to eliminate many false-positive results. Use of the blocking antibody reagent can then be reserved for confirming only specimens which are repeatedly positive. PMID- 8349768 TI - Detection of adenovirus in clinical specimens by polymerase chain reaction and liquid-phase hybridization quantitated by time-resolved fluorometry. AB - In addition to tests for the group-specific hexon antigen of adenoviruses, adenoviruses can be detected in clinical specimens by hybridization assays utilizing the widely shared base sequences of the region of the hexon gene that codes for the group-reactive determinants. We have developed a liquid-phase hybridization system with biotin- and europium-labeled probes which are reacted after DNA amplification of a 161-bp region of the hexon gene and which are quantitated by time-resolved (TR) fluorometry in streptavidin-coated microtiter wells. Polymerase chain reaction (PCR)-TR fluorometry is not a rapid test in the usual sense, but it is highly useful for specimens with inherent toxicity or with low virus yield, such as organ minces and specimens obtained late in the course of an illness. In a survey of 103 specimens tested by this method, including urine, stool, and tissue suspensions, the agreement with the hexon-specific TR fluoroimmunoassay antigen test for positive specimens was 100% and the sensitivity compared with that of virus culture was 91%. The PCR-TR fluorometry system was also shown to be advantageous as a quantitative measure of PCR products. PMID- 8349770 TI - Recovery of Borrelia burgdorferi by filtration. AB - Bacterial contamination frequently interferes with successful recovery of the Lyme spirochete from cultures of tissue from Borrelia burgdorferi-infected humans, rodents, or ticks. We used 0.20- and 0.45-microns-pore-size syringe-tip filters to recover spirochetes from cultures contaminated with other bacteria. Low concentrations (1 to 10/ml) of B. burgdorferi organisms could be recovered from cultures seeded with 1 x 10(8) to 4 x 10(8) Staphylococcus aureus, Streptococcus faecium, Escherichia coli, or Bacillus subtilis organisms per ml. We also used this technique to recover B. burgdorferi from contaminated environmental and clinical cultures of B. burgdorferi. We conclude the filtration is an efficient method for recovering Lyme spirochetes from contaminated samples and increasing the number of successful isolations of B. burgdorferi. PMID- 8349771 TI - Total cellular fatty acid composition of cultured Pneumocystis carinii. AB - Oleic acid makes up > 50% of the total fatty acids of Pneumocystis carinii grown on WI-38 cells. Oleic acid levels increased in parallel with increasing trophozoites over 7 days in culture. The fatty acid composition of P. carinii resembles that of certain fungi but differs from those of lung surfactant lipid, host cells, and fetal bovine serum. PMID- 8349772 TI - Inhibition of Acanthamoeba species by Pseudomonas aeruginosa: rationale for their selective exclusion in corneal ulcers and contact lens care systems. AB - Cocultivation of Acanthamoeba castellanii and Acanthamoeba polyphaga with live Pseudomonas aeruginosa and with broth filtrates of P. aeruginosa proved equally lethal to the Acanthamoeba spp. The P. aeruginosa-induced amebicidal activity is apparently toxin mediated and has two operative modes: it can function through binding of P. aeruginosa to the ameba membrane and in the presence of one or more P. aeruginosa exoproducts. PMID- 8349773 TI - Catheter-related Rahnella aquatilis bacteremia in a pediatric bone marrow transplant recipient. AB - Rahnella aquatilis, a rarely encountered member of the family Enterobacteriaceae, was twice isolated from the blood of a pediatric bone marrow transplant recipient. This is the first report of a pediatric case of R. aquatilis bacteremia, and it was probably related to inappropriate handling of a Hickman catheter. PMID- 8349774 TI - Novel Campylobacter-like organism resembling Helicobacter fennelliae isolated from a boy with gastroenteritis and from dogs. AB - We isolated a Campylobacter-like organism resembling Helicobacter fennelliae from a 5 1/2-year-old boy with gastroenteritis. Similar strains had been found previously in fecal specimens from healthy and diarrheic dogs. These isolates could be differentiated from H. fennelliae by a lack of catalase and arylsulfatase activities. This group of organisms seems to be homogeneous by a nonradioactive dot blot DNA hybridization assay. PMID- 8349775 TI - Sensitivity of culture compared with that of polymerase chain reaction for detection of Helicobacter pylori from antral biopsy samples. AB - Polymerase chain reaction (PCR) was used to test the sensitivity of standard bacteriological culture of Helicobacter pylori. The tests were concordant in 97% of cases. PCR did not detect more treatment failures after triple treatment than did the standard culture method. In the present study, culture was as sensitive as PCR for the detection of H. pylori. PMID- 8349776 TI - Synergy characterization for Enterococcus faecalis strains displaying moderately high-level gentamicin and streptomycin resistance. AB - Synergy of 14 Enterococcus faecalis strains displaying moderately high-level aminoglycoside resistance (MICs, 500 and 256 to 1,000 micrograms/ml for gentamicin and streptomycin, respectively) was characterized by time-kill studies. All strains proved resistant to penicillin plus the respective aminoglycoside. Strains with moderately high-level aminoglycoside resistance should be considered to exhibit high-level resistance in severe infections. PMID- 8349777 TI - Levofloxacin disk potency and tentative interpretive criteria for susceptibility tests. AB - Levofloxacin disk susceptibility test criteria were evaluated by testing 350 bacterial isolates. Either 5- or 10-micrograms disks could be used satisfactorily. A 5-micrograms levofloxacin disk with zone size breakpoints of < or = 12 mm for resistance (MIC, > or = 8.0 micrograms/ml) and > or = 16 mm for susceptibility (MIC, < or = 2.0 micrograms/ml) is recommended. PMID- 8349778 TI - Whole-cell repetitive element sequence-based polymerase chain reaction allows rapid assessment of clonal relationships of bacterial isolates. AB - Repetitive element sequence-based polymerase chain reaction (rep-PCR) enables the generation of DNA fingerprints which discriminate bacterial species and strains. We describe the application of whole-cell methods which allow specimens from broth cultures or colonies from agar plates to be utilized directly in the PCR mixture. The rep-PCR-generated DNA fingerprints obtained with whole-cell samples match results obtained with genomic DNA templates. Examples with different gram negative bacteria (e.g., Citrobacter diversus, Escherichia coli, and Pseudomonas aeruginosa) and gram-positive bacteria (e.g., Staphylococcus aureus and Streptococcus pneumoniae) are demonstrated. Rapid specimen preparation methods enable rep-PCR-based fingerprinting to be completed in several hours and, therefore, allows the timely analysis of epidemiological relationships. PMID- 8349779 TI - Ramoplanin susceptibility testing criteria. AB - Ramoplanin and mupirocin are two antimicrobial agents that may be applied topically. They had similar potencies against susceptible gram-positive cocci, but they differed in their spectra of activity. In plastic microdilution trays, the in vitro activity of ramoplanin was slightly diminished but that activity was restored by the addition of bovine serum albumin (0.02%). Susceptible strains were defined as those for which MICs of ramoplanin were < or = 2.0 micrograms/ml (without bovine serum albumin) and which had > or = 11-mm zones around 60 micrograms ramoplanin disks. Criteria for a resistant category cannot be defined at this time. PMID- 8349780 TI - Use of immunoelectron microscopy to demonstrate Francisella tularensis. AB - Three immunoelectron microscopy (IEM) methods were employed to show laboratory cultivated Francisella tularensis. By the IEM assays, F. tularensis was distinguished from four antigenically distinct gram-negative bacteria. IEM should be a valuable tool for confirming presumptive isolates of F. tularensis and may potentially be useful for demonstrating other medically important bacteria. PMID- 8349781 TI - Evaluation of the L-pyrrolidonyl-beta-naphthylamide hydrolysis test for the differentiation of members of the families Enterobacteriaceae and Vibrionaceae. AB - A simple, rapid, and inexpensive spot test incorporating the substrate pyrrolidonyl naphthylamide was used to examine pyrrolidonyl peptidase activity among 800 bacterial strains belonging to the families Enterobacteriaceae and Vibrionaceae. The pyrrolidonyl naphthylamide test was found to be particularly useful in separating Citrobacter spp. (100% positive) from Salmonella spp. (0.4% positive) and Escherichia coli (0% positive). Furthermore, it would appear to offer a safer alternative to the traditional potassium cyanide test for differentiating citrobacters from salmonellae. PMID- 8349782 TI - Analysis of serotype-specific antibodies to Trichosporon cutaneum types I and II in patients with summer-type hypersensitivity pneumonitis with monoclonal antibodies to serotype-related polysaccharide antigens. AB - Summer-type hypersensitivity pneumonitis is the most prevalent type of hypersensitivity pneumonitis in Japan. We constructed a sandwich enzyme-linked immunosorbent assay system for diagnosis of summer-type hypersensitivity pneumonitis in which monoclonal antibodies were used to bind serotype-related polysaccharides to plastic plates, and this system was proven to have sufficient sensitivity and specificity. PMID- 8349783 TI - Identification of M types of group A streptococci. PMID- 8349784 TI - Usefulness of DNA fingerprinting in combating tuberculosis. PMID- 8349785 TI - Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes. AB - Oxidatively modified low density lipoprotein (Ox-LDL) is a known chemoattractant for monocytes. Here we demonstrate, using a modified Boyden chamber assay, that human peripheral blood T lymphocytes, but not B lymphocytes, also respond chemotactically to Ox-LDL, showing a threefold increase over control and an optimum response at 10 micrograms/ml. Copper and endothelial cell-oxidized LDL and beta-VLDL were used and gave similar results. The activity was not chemokinetic and native LDL possessed no chemoattractant activity. The chemoattractant activity was found to reside in the lipid fraction of Ox-LDL. Lysophosphatidylcholine is a major phospholipid component of Ox-LDL and is known to be chemotactic for monocytes. We show that lysophosphatidylcholine is also chemotactic for T lymphocytes with a maximal fourfold increase at 10 microM. Nonmetabolizable analogues of lysophosphatidylcholine had no such chemotactic effect. Thus, Ox-LDL, by virtue of its lysophosphatidylcholine content, may contribute to the recruitment of both T lymphocytes and monocytes into developing atherosclerotic lesions. PMID- 8349788 TI - A circulating substance cross-reacting with antiimidazoline antibodies. Detection in serum in relation to essential hypertension. AB - It has been shown in various mammal species that clonidine, a well known centrally acting hypotensive agent, acts through the activation of imidazoline receptors (IRs) in the nucleus reticularis lateralis (NRL) of the brainstem. Specific binding sites sensitive to imidazolines and insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, other than catecholamines, should exist for these IRs. Such a ligand could play a role in the pathophysiology of human essential hypertension. Therefore, we developed two RIAs with polyclonal and monoclonal anticlonidine antibodies. These antibodies presented specificity spectra similar to that of the IRs: they bound imidazolines and not catecholamines at all. These RIAs were used to detect imidazoline-like immunoreactivity in the human serum. Immunoreactive substance was measured in 26 normotensive subjects' sera, and specificity of interaction between antibodies and sera was verified. None of the known endogenous substances tested so far were able to interact with the two antibodies. Immunoreactivity in 32 essential hypertensive patients' sera proved higher in approximately 30% of cases. Values of immunoreactivity positively correlated with the mean arterial pressure values. This study demonstrates the existence of an "imidazoline-like" immunoreactive substance in the human serum with high levels in some hypertensive patients. PMID- 8349786 TI - Rapid in vivo transport and catabolism of human apolipoprotein A-IV-1 and slower catabolism of the apoA-IV-2 isoprotein. AB - Apolipoprotein (apo) A-IV is a polymorphic, intestinally derived apolipoprotein that is genetically linked to and similar in structure to apoA-I, the major apolipoprotein in high density lipoproteins (HDL). ApoA-IV plays a potentially important role in lipoprotein metabolism and reverse cholesterol transport, but its in vivo metabolism is poorly understood. In order to gain insight into factors modulating apoA-IV metabolism in humans, the in vivo kinetics of the two major human apoA-IV isoproteins apoA-IV-1 and apoA-IV-2 were investigated in normolipidemic human subjects. 131I-apoA-IV-1 and 125I-apoA-IV-2 were reassociated with autologous plasma and injected into study subjects. Analysis of the kinetic data revealed a rapid mean fractional catabolic rate (FCR) for apoA IV-1 of 2.42 +/- 0.11 d-1. The mean production, or transport, rate of apoA-IV-1 was 16.3 +/- 1.4 mg/kg per d. Plasma apoA-IV concentrations were highly correlated with apoA-IV production rate (r = 0.84, P < 0.001) and not correlated with apoA-IV fractional catabolic rate (r = 0.25, P = NS). The mean FCR of apoA IV-2 was 2.21 +/- 0.10 d-1. In the ten subjects in whom 131I-apoA-IV-1 and 125I apoA-IV-2 were simultaneously injected, the FCR of apoA-IV-2 was significantly slower by paired t test (P = 0.003). The FCR of apoA-IV-2 in an apoA-IV-2/2 homozygote was only 1.49 d-1, substantially slower than in all other subjects. We conclude that: (a) apoA-IV is a rapidly catabolized apolipoprotein in humans, with a fractional catabolic rate more than 10 times greater than that of apoA-I; (b) apoA-IV has a high absolute transport rate similar to that of apoA-I; (c) plasma levels of apoA-IV are primarily determined by apoA-IV production rate in normolipidemic subjects; and (d) the fractional catabolic rate of the common variant apoA-IV-2 is slower than that of the wild-type apoA-IV-1. PMID- 8349787 TI - Identification of the fetal liver cytochrome CYP3A7 in human endometrium and placenta. AB - Placenta and endometrium carry out steroidogenic biotransformation reactions such as 6-beta-hydroxylation of cortisol, a reaction characteristic of the dominant family of cytochromes P450 in human liver, CYP3A. To investigate the possible role in these extrahepatic tissues of the CYP3A microsomal hemoproteins, we analyzed placental and endometrial microsomes on Western blots developed with an anti-human CYP3A antibody. We found an immunoreactive 51,500 D protein that migrated between CYP3A3 (HLp) and CYP3A5 (HLp2) identical with CYP3A7 (HFLa). CYP3A7, a form found prominently in human fetal liver microsomes, was first isolated as a liver 16-alpha-dehydroepiandrosterone-sulfate hydroxylase. Northern blot analysis of total RNA isolated from placenta or from endometrium demonstrated a single band that cross-hybridized with a CYP3A7 cDNA. Amplification of the same RNA samples with the use of primers specific for CYP3A7, produced a 552-bp segment that had the predicted size and the same DNA sequence as does liver CYP3A7 cDNA. Hybridizable endometrial CYP3A7 mRNA was detected more frequently (six of seven samples) and in higher amounts (approximately 12-fold higher) in pregnant compared with nonpregnant women (4 of 12 samples). In addition, during the secretory phase of the menstrual cycle CYP3A7 expression was sixfold higher than in the one sample from the proliferative phase that had detectable CYP3A7 mRNA. Moreover, the amounts of placental and endometrial CYP3A7 mRNA and protein increased substantially from the first to the second trimester of pregnancy. We conclude that placenta and endometrium express the same P450 as is found in fetal liver. These tissues represent a previously unrecognized and quantitatively important site for 6-beta hydroxylation and 16-alpha-hydroxylation of specific steroid precursors, possibly for protection of the fetus from the toxic effects of endogenous steroids and foreign substrates. PMID- 8349789 TI - Altered renal kallikrein and renin gene expression in nephrotic rats and modulation by converting enzyme inhibition. AB - Urinary kallikrein excretion (UKE) is decreased in rats with passive Heymann nephritis (PHN), but increases after converting enzyme inhibition (CEI). Although CEI potentiates bradykinin activity, neither the effect of CEI on kallikrein secretion nor the abnormal renal kallikrein metabolism in PHN has been examined previously. To determine the mechanism by which CEI increases UKE, normal rats and PHN received enalapril, 40 mg/kg per d orally for 4 d. UKE was 85% lower in PHN than in normals and increased in both groups after CEI, although UKE in PHN remained significantly less than in normals. Kallikrein mRNA was significantly lower in PHN compared to normals but not in PHN treated with CEI and did not change in normal rats. Renin mRNA was significantly lower in PHN, and was stimulated by CEI only in normals. Renal kallikrein and renin content were not different and were not altered by CEI. Both kallikrein and renin genes appear to be transcriptionally suppressed in rats with PHN and the depressed kallikrein mRNA levels can be reversed by CEI. The modest increase in UKE despite normalization of kallikrein mRNA after CEI suggests that there is also a posttranscriptional defect in synthesis and/or secretion of kallikrein. PMID- 8349790 TI - Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers. AB - Newly described distinct associations of HLA class II genes with ulcerative colitis (UC) (DR2) and Crohn's disease (CD) (DR1/DQ5) provide strong evidence for genetic heterogeneity of susceptibility between these two forms of inflammatory bowel disease. A familial distribution of antineutrophil cytoplasmic antibodies (ANCAs, a subclinical marker of UC) in UC families has further implied the existence of heterogeneity within UC. To test the hypothesis that the heterogeneity within UC indicated by ANCAs has a genetic basis that resides within the HLA region, we studied 89 UC cases and an ethnically matched control group (n = 50). Serological and molecular typing techniques were applied to define HLA class II genes (DR, DQ). ANCAs were detected using an enzyme-linked immunosorbent assay, and positive values were confirmed by indirect immunofluorescence. We observed that ANCA-positive UC patients (n = 70) had a significantly increased frequency of DR2 compared with ANCA-negative controls (n = 46) (44% vs 22%, P = 0.01). In contrast, the frequency of DR2 in ANCA-negative UC cases (21%) was virtually identical to that in controls (22%, P = 0.9). Furthermore, the ANCA-negative UC patients had an increase in the DR4 allele compared with ANCA-positive UC (P = 0.004). Thus, with the combination of a subclinical marker (ANCAs) and molecular genetic markers, genetic heterogeneity has been demonstrated within UC: ANCA-positive UC associated with DR2, and ANCA negative UC likely associated with DR4. PMID- 8349791 TI - Adenoviral-mediated gene transfer to rabbit synovium in vivo. AB - Currently, treatment for rheumatoid arthritis and other inflammatory arthropathies is often ineffective in ameliorating the progression of the disease, particularly the invasive destruction of cartilage and bone by rheumatoid synovium. Multiple aspects of this inflammatory process are mediated by the synovial lining cells (synoviocytes). Genetic modification of these cells in vivo represents a potential method for the treatment of these conditions. In this report, we describe a novel technique for the genetic transduction of synovial lining cells in vivo using recombinant adenoviral vectors and intraarticular injection techniques. Purified high titer suspensions of a recombinant adenoviral vector containing the gene for Escherichia coli beta galactosidase (AdCMVlacZ) were directly injected into the hind knees of New Zealand white rabbits. Synovial tissues were then examined for transgenic lacZ expression using a combination of in situ staining for beta-galactosidase activity, immunohistochemical staining, and transmission electron microscopy. High efficiency gene transfer and lacZ expression was observed in both type A and type B synoviocytes throughout the articular and periarticular synovium of the rabbit knee, with continued expression of transgenic lacZ detected for > or = 8 wk after infection. PMID- 8349792 TI - Evidence for the role of nitric oxide in macula densa control of glomerular hemodynamics. AB - There is evidence that nitric oxide, an endothelium-derived relaxing factor, may be produced by the macula densa, as well as by blood vessels, within the kidney. To examine the role of nitric oxide in macula densa control of glomerular hemodynamics directly, we performed in vitro microperfusions of both rabbit afferent arterioles (with the glomerulus intact) and adherent tubular segments consisting of portions of the thick ascending limb, macula densa, and early distal tubule. While keeping afferent arteriolar pressure constant at 60 mmHg, we examined the effect of Nw-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, added to a macula densa perfusate. When the macula densa perfusate was changed from low to high NaCl, the diameter of the arterioles decreased from 16.3 +/- 1.0 to 14.0 +/- 1.1 microns (n = 10; P < 0.001). Addition of 10(-5) M L-NAME to the high NaCl solution further decreased the diameter to 11.9 +/- 1.1 microns (P < 0.001). In contrast, when macula densa perfusion was maintained with the low NaCl solution, addition of L-NAME had no effect. L-NAME induced constriction was completely reversed by adding 10(-3) M L-arginine (the precursor of nitric oxide) but not D-arginine (an inactive isomer) to the macula densa perfusate. We confirmed that perfusing the macula densa with L-NAME did not affect the vasodilator action of acetylcholine added to the lumen of the afferent arteriole, indicating that NO synthesis by the arteriole was not altered. Thus, our findings suggest that the macula densa may produce nitric oxide, which in turn modulates the afferent arteriolar constriction induced by high concentrations of NaCl at the macula densa. PMID- 8349794 TI - Just (don't) do it. PMID- 8349793 TI - A gene differentially expressed in the kidney of the spontaneously hypertensive rat cosegregates with increased blood pressure. AB - The role of the kidney in initiating hypertension has been much debated. Here we demonstrate that a recently identified gene of yet unknown function, termed SA, which is differentially expressed in the kidney of the spontaneously hypertensive rat, cosegregates with an increase in blood pressure in F2 rats derived from a cross of the spontaneously hypertensive rat with normotensive Wistar-Kyoto rats, accounting for 28 and 21% of the genetic variability in systolic and diastolic blood pressures, respectively. Further, the genotype at this locus appears to determine the level of expression of the gene in the kidney. The findings provide strong evidence for a primary genetic involvement of the kidney in hypertension. PMID- 8349795 TI - Murine models for study of lipoprotein metabolism and atherosclerosis. PMID- 8349796 TI - Insulin-like growth factor-1 stimulation of lymphopoiesis. AB - We show that treatment of adult mice with recombinant human insulin-like growth factor 1 (rhIGF-1) induces striking modifications in lymphocyte number and function. 9-mo-old male mice received rhIGF-1 (4 mg/kg per d) or its excipient by subcutaneous infusion from osmotic minipumps for 7 or 14 d. Mice were weighed daily and bled at sacrifice; the spleen and thymus were harvested and single cell suspensions were made for analysis of cell phenotype and cell number. The responses of splenocytes to mitogens (concanavalin A, lipopolysaccharide, and pokeweed mitogen), alloantigens and dinitrophenyl ovalbumin were measured. After either 7 or 14 d of treatment, rhIGF-1 had an overall whole-body anabolic effect, resulting in increased body and organ weights with prominent increases in the weight of the spleen and thymus. Furthermore, the rhIGF-1 treated mice were normoglycemic but had reduced blood urea nitrogens, again reflecting the anabolic activity of rhIGF-1. The increased spleen and thymus weights were associated with a large increase in the number of lymphocytes in both organs. In addition to an increase in T cells, specifically CD4+ T cells, a dramatic increase in splenic B cells was also observed. This increase was accompanied by an enhanced responsiveness to dinitrophenyl ovalbumin resulting in increased immunoglobulin production. However, despite the increases in cellularity, there was a decrease in the in vitro responses of spleen cells to mitogens after 7 d of rhIGF-1 treatment. In contrast, treatment with rhIGF-1 for 14 d increased both the cell number and mitogenic responses of splenocytes suggesting that some time is required for the cells populating the peripheral organs to gain mitogenic responsiveness. It is clear from these data that rhIGF-1, at doses that have whole-body anabolic activity, can expand cell number in lymphoid tissue in a normal adult mouse. These dual effects of rhIGF-1, of increasing lymphocyte number and activity, indicate that, in a normal adult animal, rhIGF-1 can cause major changes in lymphoid tissues that are of potential benefit to the functioning of the immune system. PMID- 8349797 TI - Electrical properties of the rabbit cortical collecting duct from obstructed and contralateral kidneys after unilateral ureteral obstruction. AB - Electrophysiological techniques were used to determine the electrical properties of the collecting duct (CD) cell in the isolated cortical collecting duct from obstructed (UUOOK) and contralateral (UUOCK) kidneys in rabbits 24 h after unilateral ureteral obstruction (UUO); results were compared with those from sham operated kidneys. The lumen-negative transepithelial voltage and the basolateral membrane voltage (VB) were decreased in the UUOOK, and increased in the UUOCK. The transepithelial conductance (GT) was decreased in parallel with an increase in the fractional apical membrane resistance (fRA) and a decrease in apical membrane conductance in the UUOOK. By contrast, the GT was increased in parallel with increases in apical and basolateral membrane conductances in the UUOCK. The amiloride-sensitive changes in apical membrane voltage (VA), GT and fRA were lower in the UUOOK, but greater in the UUOCK. The changes in VA and GT upon raising the perfusate K+ concentration and upon addition of luminal Ba2+ were decreased in the UUOOK, and increased in the UUOCK. Addition of ouabain to the bath resulted in a smaller depolarization of VB in the UUOOK, but in a greater depolarization in the UUOCK. Upon lowering bath Cl-, the change in basolateral membrane electromotive force (delta EMF) was increased in the UUOOK, and decreased in the UUOCK. Reversely, upon raising bath K+, the delta EMF was decreased in the UUOOK, and increased in the UUOCK. We conclude: (a) the conductances of Na+ and K+ in the apical membrane, and active Na(+)-K+ pump activity and relative K+ conductance in the basolateral membrane are decreased in the UUOOK, and increased in the UUOCK; (b) the relative basolateral membrane Cl- conductance was increased in the UUOOK, and decreased in the UUOCK. PMID- 8349798 TI - An inbred line of transgenic mice expressing an internally deleted gene for type II procollagen (COL2A1). Young mice have a variable phenotype of a chondrodysplasia and older mice have osteoarthritic changes in joints. AB - Studies were carried out on a line of transgenic mice that expressed an internally deleted COL2A1 gene and developed a phenotype resembling human chondrodysplasias (Vandenberg et al. 1991. Proc. Natl. Acad. Sci. USA. 88:7640 7644. Marked differences in phenotype were observed with propagation of the mutated gene in an inbred strain of mice in that approximately 15% of the transgenic mice had a cleft palate and a lethal phenotype, whereas the remaining mice were difficult to distinguish from normal littermates. 1-d- and 3-mo-old transgenic mice that were viable showed microscopic signs of chondrodysplasia with reduced amounts of collagen fibrils in the cartilage matrix, dilatation of the rough surfaced endoplasmic reticulum in the chondrocytes, and decrease of optical path difference in polarized light microscopy. The transgenic mice also showed signs of disturbed growth as evidenced by lower body weight, lower length and weight of the femur, decreased bone collagen, decreased bone mineral, and decreased resistance of bone to breakage. Comparisons of mice ranging in age from 1 d to 15 mo demonstrated that there was decreasing evidence of a chondrodysplasia as the mice grew older. Instead, the most striking feature in the 15-mo-old mice were degenerative changes of articular cartilage similar to osteoarthritis. PMID- 8349799 TI - T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase. AB - Adenosine deaminase (ADA) deficiency causes severe combined immune deficiency (SCID) by interfering with the metabolism of deoxyadenosine, which is toxic to T lymphocytes at all stages of differentiation. Enzyme replacement with polyethylene glycol-modified ADA (PEG-ADA) has been previously shown to correct deoxyadenosine metabolism and improve mitogen-induced T lymphocyte proliferation. We studied the biochemical and immunologic effects of PEG-ADA in two infants with ADA-deficient SCID. While in a catabolic state, higher doses of PEG-ADA than previously described were required to normalize deoxyadenosine metabolism. After biochemical improvement, the patients recovered immune function in a pattern similar to that observed in normal thymic ontogeny and in patients with immunological reconstitution after bone marrow transplantation. Immune reconstitution was marked by the sequential appearance in the peripheral blood of phenotypic T lymphocytes corresponding to successive stages of thymic differentiation. Functional reconstitution was marked by the successive appearance of mitogen responses dependent on exogenous in vitro IL-2, mitogen responses not requiring exogenous IL-2, antigen-specific responses dependent on exogenous IL-2, and finally, antigen-specific responses not requiring exogenous IL-2. Natural killer function was tested in one patient and normalized with PEG ADA therapy. Optimal PEG-ADA therapy appears to normalize thymic differentiation in ADA-deficient SCID, resulting in normal antigen-specific immune function. PMID- 8349800 TI - Altered aldose reductase gene regulation in cultured human retinal pigment epithelial cells. AB - Aldose reductase (AR2), a putative "hypertonicity stress protein" whose gene is induced by hyperosmolarity, protects renal medullary cells against the interstitial hyperosmolarity of antidiuresis by catalyzing the synthesis of millimolar concentrations of intracellular sorbitol from glucose. Although AR2 gene induction has been noted in a variety of renal and nonrenal cells subjected to hypertonic stress in vitro, the functional significance of AR2 gene expression in cells not normally exposed to a hyperosmolar milieu is not fully understood. The physiological impact of basal AR2 expression in such cells may be limited to hyperglycemic states in which AR2 promotes pathological polyol accumulation, a mechanism invoked in the pathogenesis of diabetic complications. Since AR2 overexpression in the retinal pigment epithelium has been associated with diabetic retinopathy, the regulation of AR2 gene expression and associated changes in sorbitol and myo-inositol were studied in human retinal pigment epithelial cells in culture. The relative abundance of aldehyde reductase (AR1) and AR2 mRNA was quantitated by filter hybridization of RNA from several human retinal pigment epithelial cell lines exposed to hyperglycemic and hyperosmolar conditions in vitro. AR2 but not AR1 mRNA was significantly increased some 11- to 18-fold by hyperosmolarity in several retinal pigment epithelial cell lines. A single cell line with a 15-fold higher basal level of AR2 mRNA than other cell lines tested demonstrated no significant increase in AR2 mRNA in response to hypertonic stress. This cell line demonstrated accelerated and exaggerated production of sorbitol and depletion of myo-inositol upon exposure to 20 mM glucose. Therefore, abnormal AR2 expression may enhance the sensitivity of cells to the biochemical consequences of hyperglycemia potentiating the development of diabetic complications. PMID- 8349801 TI - Human neutrophil-mediated fungistasis against Histoplasma capsulatum. Localization of fungistatic activity to the azurophil granules. AB - Human neutrophils (PMN) demonstrated potent fungistatic activity against Histoplasma capsulatum (Hc) yeasts in a sensitive microassay that quantifies the growth of yeasts by the incorporation of [3H]leucine. At a PMN:yeast ratio of 1:2, PMN inhibited the growth of yeasts by 37%. Maximum inhibition of 85% to 95% was achieved at a PMN/yeast ratio of 10:1 to 50:1. Opsonization of the yeasts in fresh or heat-inactivated serum was required for PMN-mediated fungistasis, but ingestion of the yeasts was not required. Recognition and phagocytosis of opsonized yeasts was via PMN complement receptor (CR) type 1 (CR1), CR3, and FcRIII (CD16). PMN fungistatic activity was evident by 2 h, was maximum at 24 h, and persisted up to 5 d. In contrast, yeasts multiplied within monocytes to a greater extent than in culture medium alone. PMN from three patients with chronic granulomatous disease (CGD) inhibited the growth of Hc yeasts by an average of 97%, compared with 86% in three normal controls. Furthermore, preincubation of PMN with the lysosomotropic agent NH4Cl inhibited fungistatic activity in a concentration-dependent manner. Finally, experiments with subcellular fractions of PMN demonstrated that the principal component of the fungistatic activity of PMN was localized in the azurophil granules. These data demonstrate that human PMN possess potent fungistatic activity against Hc yeasts and further show that fungistasis is mediated by antimicrobial agents contained in the azurophil granules. PMID- 8349802 TI - The effect of oxidized lipids in the diet on serum lipoprotein peroxides in control and diabetic rats. AB - The levels of oxidized serum lipoproteins are increased in humans and animals with diabetes. We have examined the contribution of dietary oxidized lipids on the levels of oxidized lipoproteins. In both control and streptozocin induced diabetic rats, the oxidized lipid content of mesenteric lymph chylomicrons (CM) increased when increasing quantities of oxidized lipids were administered intragastrically. However, at all levels of administered oxidized lipids, the quantity of oxidized lipids in CM was greater in the diabetic animals. These results indicate that oxidized lipids are absorbed and packaged into CM and suggest that there is increased absorption of oxidized lipids in diabetic animals. In nondiabetic rats fed a fat-free diet, the levels of oxidized lipids in their serum lipoproteins were very low. When oxidized lipids were added to the diet, the quantity of peroxides in serum lipoproteins increased about fivefold. In diabetic animals fed a fat-free diet, there were also very low levels of oxidized lipids in their serum lipoproteins, and there was no difference between control and diabetic rats. However, when diabetic animals were fed a diet containing oxidized lipids, the quantity of oxidized lipids in their serum lipoproteins increased 16-fold and were significantly greater than in controls. Thus, in both control and diabetic rats the quantity of oxidized lipids in the diet largely determines the levels of oxidized lipids in circulating lipoproteins. However, in diabetic animals the effect of diet is more pronounced. Together with the CM studies, these results demonstrate that dietary oxidized lipids make a major contribution to the levels of oxidized lipids in circulating lipoproteins and indicate that increased absorption of oxidized lipids in diabetic animals may play a role in the elevation of oxidized lipoproteins observed in this disorder. PMID- 8349803 TI - Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. AB - We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a double-blind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Th1-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance. PMID- 8349804 TI - Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. AB - The effects of age, atherosclerosis, hypertension, and hypercholesterolemia on vascular function of the coronary circulation were studied by subselective intracoronary infusions of acetylcholine, which releases endothelium-derived relaxing factor, and papaverine, which directly relaxes vascular smooth muscle, in normal patients (n = 18; no risk factors for coronary artery disease), in patients with evidence of early atherosclerosis but normal cholesterol levels and normal blood pressure (n = 12), in patients with hypertension without left ventricular hypertrophy (n = 12), and in patients with hypercholesterolemia (n = 20). Papaverine-induced maximal increases in coronary blood flow were significantly greater in normals, but no differences were noted between the groups of patients with early atherosclerosis, with hypertension, and with hypercholesterolemia. The capacity of the coronary system to increase blood flow in response to acetylcholine was similar in normal and normocholesterolemic patients with epicardial atherosclerosis and/or hypertension but was significantly impaired in patients with hypercholesterolemia, irrespective of evidence of epicardial atherosclerotic lesions. Age (r = -0.62, P < 0.0001) and total serum cholesterol levels (r = -0.70; P < 0.0001) were the only significant independent predictors of a blunted coronary blood flow response to acetylcholine. Thus, hypercholesterolemia and advanced age selectively impair endothelium-mediated relaxation of the coronary microvasculature in response to acetylcholine, whereas endothelial dysfunction is restricted to epicardial arteries in age-matched normocholesterolemic patients with evidence of coronary atherosclerosis and/or hypertension. PMID- 8349805 TI - Human keratinocytes are a major source of cutaneous platelet-derived growth factor. AB - PDGF has been implicated as one of the principal mitogens involved in cutaneous wound healing. While it has been previously reported that both platelets and monocytes are a source of PDGF in human dermal wound repair, the production of PDGF by human keratinocytes has not yet been described. In this manuscript, we report the production of PDGF by cultured human keratinocytes. Both PDGF A and B chain mRNA can be detected in cultured cells. While only PDGF-AA polypeptide is found in significant levels in keratinocyte-conditioned culture media, all three PDGF isoforms (AA, AB, and BB) are present in detergent-solubilized cell extracts. No evidence of PDGF receptor expression was observed in cultured keratinocytes when analyzed for either mRNA levels or polypeptide expression, suggesting that PDGF does not play an autocrine role in keratinocyte growth. Analysis of cryosections of human cutaneous wounds by immunostaining for PDGF showed that both PDGF A and B chain is constitutively expressed in normal epidermis, as well as in newly reconstituted wound epidermis. No evidence for PDGF receptor polypeptide expression in the epidermis was detected by immunostaining of cryosections. PMID- 8349806 TI - Extracellular proteolysis in the adult murine brain. AB - Plasminogen activators are important mediators of extracellular metabolism. In the nervous system, plasminogen activators are thought to be involved in the remodeling events required for cell migration during development and regeneration. We have now explored the expression of the plasminogen activator/plasmin system in the adult murine central nervous system. Tissue-type plasminogen activator is synthesized by neurons of most brain regions, while prominent tissue-type plasminogen activator-catalyzed proteolysis is restricted to discrete areas, in particular within the hippocampus and hypothalamus. Our observations indicate that tissue-type plasminogen activator-catalyzed proteolysis in neural tissues is not limited to ontogeny, but may also contribute to adult central nervous system physiology, for instance by influencing neuronal plasticity and synaptic reorganization. The identification of an extracellular proteolytic system active in the adult central nervous system may also help gain insights into the pathogeny of neurodegenerative disorders associated with extracellular protein deposition. PMID- 8349807 TI - Glomerular filtration and tubular reabsorption of albumin in preproteinuric and proteinuric diabetic rats. AB - Microalbuminuria (26-250 mg/d) is considered to be an indicator of incipient diabetic nephropathy in humans in insulin-dependent diabetes (IDD). However, before microalbuminuria is observed, glomerular alterations, such as glycosylation of the glomerular basement membrane and glomerular hyperfiltration, in IDD may result in increased filtration of albumin before any observed increase in albumin excretion. Glomerular and tubular albumin kinetics were examined in streptozotocin (65 mg/kg body wt, i.v.) diabetic, Munich-Wistar rats at 7-10 (untreated) and 50-70 d (poorly controlled with small doses of insulin) after the onset of diabetes and compared with nondiabetic controls. Additional rats in each condition received acute lysine treatment to prevent tubular protein reabsorption. Urinary albumin excretion and nonvascular albumin distribution volumes were measured in the renal cortex and compared with morphometric measurements of interstitial space and the proximal tubule to assess intracellular uptake of albumin in the proximal tubule. Urinary albumin excretion under anesthesia was not different in 7-10-d IDD versus controls (19 +/- 3 vs. 20 +/- 3 micrograms/min) but increased in the 50-70-d IDD (118 +/- 13 micrograms/min, P < 0.05). Lysine treatment resulted in increased albumin excretion compared with respective nontreatment in 7-10-d IDD (67 +/- 10 micrograms/min, P < 0.05) but not in controls (30 +/- 6 micrograms/min) or in 50 70-d IDD (126 +/- 11 micrograms/min). Glomerular filtration rate was increased both in 7-10-d IDD (2.7 +/- 0.1 ml/min, P < 0.05) and in 50-70-d IDD (2.6 +/- 0.1 ml/min, P < 0.05) compared with control (2.2 +/- 0.1 ml/min). Calculated urinary space albumin concentrations increased early in IDD with 2.5 +/- 0.4 mg% in 7-10 d IDD and 4.9 +/- 0.6 mg% in 50-70-d IDD compared with control (1.4 +/- 0.3 mg%). The increase in filtration of albumin is in excess of that attributable to hyperfiltration before increased albumin excretion early in diabetes. In 50-70-d IDD, absolute tubular reabsorption of albumin is decreased, correlating to the decrease in brush border height of the proximal tubule. PMID- 8349808 TI - Suppression of growth hormone (GH) secretion by a selective GH-releasing hormone (GHRH) antagonist. Direct evidence for involvement of endogenous GHRH in the generation of GH pulses. AB - To study the potential involvement of growth hormone-releasing hormone (GHRH) in the generation of growth hormone (GH) pulses in humans we have used a competitive antagonist to the GHRH receptor, (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2(GHRH-Ant). Six healthy young men were given a bolus injection of GHRH-Ant 400 micrograms/kg body wt or vehicle at 2200 h and nocturnal GH concentrations were assessed by every 10 min blood sampling until 0800 h. Integrated total and pulsatile GH secretion were suppressed during GHRH-Ant treatment by 40 +/- 6 (SE) % and 75 +/- 5%, respectively. GHRH-Ant suppressed maximum (7.6 +/- 2.2 vs 1.8 +/- 0.5 micrograms/liter; P < 0.001) and mean (3.3 +/- 1.0 vs 1.1 +/- 0.2 micrograms/liter; P = 0.02) GH pulse amplitudes. There was no change in integrated nonpulsatile GH levels, pulse frequency, or interpulse GH concentration. GHRH-Ant 400 micrograms/kg also suppressed the GH responses to intravenous boluses of GHRH 0.33 micrograms/kg given 1, 6, 12, and 24 h later by 95, 81, 59, and 4%, respectively. In five healthy men, the responses to 10-fold larger GHRH boluses (3.3 micrograms/kg) were suppressed by 82 and 0%, 1 and 6 h after GHRH-Ant 400 micrograms/kg, respectively. These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans. PMID- 8349809 TI - Effects of carbonic anhydrase inhibition on ventilation-perfusion matching in the dog lung. AB - Lung carbonic anhydrase (CA) permits rapid pH responses when changes in regional ventilation or perfusion alter airway and alveolar PCO2. These pH changes affect airway and vascular resistances and lung compliance to optimize the balance of regional ventilation (VA) and perfusion (Q) in the lung. To test the hypothesis that these or other CA-dependent mechanisms contribute to VA/Q matching, we administered acetazolamide (25 mg/kg intravenously) to six anesthetized and paralyzed dogs and measured VA/Q relationships before and after CA inhibition by the multiple inert gas elimination technique. Four other groups of dogs were studied to control for possible confounding effects of time under anesthesia and nonselective CA inhibition by acetazolamide: (a) saline placebo as a control for duration of anesthesia, (b) 4% CO2 inhalation to mimic systemic CO2 retention, (c) 1 mg/kg benzolamide (a selective renal CA inhibitor) or 0.5 meq/kg HCl to mimic systemic metabolic acidosis, and (d) 500 mg/kg 4,4'-dinitrostilbene-2,2' disulfonate (an inhibitor of red cell band 3 protein) to mimic the respiratory acidosis arising from an intracapillary block to rapid mobilization of plasma HCO3- in CO2 exchange. Acetazolamide increased VA/Q mismatch and reduced arterial PO2 measured at equilibrium but these did not occur in the control group. There was no deterioration in VA/Q matching when systemic respiratory acidosis produced either by CO2 inhalation or 4,4'-dinitrostilbene-2,2'-disulfonate or metabolic acidosis (benzolamide or HCl) were imposed to mimic the effects of acetazolamide apart from its inhibition of lung CA. These results support the concept that lung CA subserves VA/Q matching in the normal lung. PMID- 8349810 TI - A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C. AB - Streptococcus pyogenes (group A Streptococcus) has re-emerged in recent years as a cause of severe human disease. Because extracellular products are involved in streptococcal pathogenesis, we explored the possibility that a disease isolate expresses an uncharacterized superantigen. We screened culture supernatants for superantigen activity with a major histocompatibility complex class II-dependent T cell proliferation assay. Initial fractionation with red dye A chromatography indicated production of a class II-dependent T cell mitogen by a toxic shock-like syndrome (TSLS) strain. The amino terminus of the purified streptococcal superantigen was more homologous to the amino termini of staphylococcal enterotoxins B, C1, and C3 (SEB, SEC1, and SEC3), than to those of pyrogenic exotoxins A, B, C or other streptococcal toxins. The molecule, designated SSA, had the same pattern of class II isotype usage as SEB in T cell proliferation assays. However, it differed in its pattern of human T cell activation, as measured by quantitative polymerase chain reaction with V beta-specific primers. SSA activated human T cells that express V beta 1, 3, 15 with a minor increase of V beta 5.2-bearing cells, whereas SEB activated V beta 3, 12, 15, and 17-bearing T cells. Immunoblot analysis of 75 disease isolates from several localities detected SSA production only in group A streptococci, and found that SSA is apparently confined to only three clonal lineages as defined by multilocus enzyme electrophoresis typing. Isolates of one of these lineages, (electrophoretic type 2) are strongly associated with TSLS. The data identify SSA as a novel streptococcal superantigen that appears to be more related structurally to staphylococcal enterotoxins than to streptococcal exotoxins. Because abundant SSA production is apparently confined to only three streptococcal clonal lineages, the data also suggest that the SSA gene has only recently been acquired by S. pyogenes. PMID- 8349811 TI - Angiotensin II increases glucose utilization during acute hyperinsulinemia via a hemodynamic mechanism. AB - To determine whether hemodynamic changes can modulate insulin action in vivo, we administered angiotensin II (AII) to normal men under three separate, euglycemic conditions. First, in the presence of physiological hyperinsulinemia (approximately 115 microU/ml), infusion of AII at rates of 2, 10, and 20 ng/min per kg caused significant elevations of blood pressure, whole-body glucose clearance, and plasma insulin concentrations in an AII dose-dependent manner. Second, in the presence of plasma insulin concentrations that stimulate glucose transport maximally (approximately 5,000 microU/ml), AII infusions increased whole-body glucose clearance without enhancing glucose extraction across the leg. Third, in the presence of basal insulin concentrations (approximately 13 microU/ml), AII infusions had no effect on whole-body glucose turnover or leg glucose extraction. Thus, AII enhanced whole-body glucose utilization without directly stimulating glucose transport in a major skeletal muscle bed. To evaluate a possible hemodynamic mechanism for the effects of AII on glucose utilization, we measured blood flow to two areas that differ in their sensitivity to insulin: the kidneys and the leg. We found that AII redistributed blood flow away from the predominantly insulin-independent tissues of the kidney and toward the insulin-sensitive tissues of the leg during both sham and hyperinsulinemic glucose clamps. The redistribution of flow had no effect on whole-body glucose turnover when leg glucose uptake was unstimulated (sham clamps). However, when leg glucose uptake was activated by insulin, the redistribution of flow caused a net increase in whole-body glucose utilization. Our findings indicate that hemodynamic factors can modulate insulin action in vivo. Furthermore, our results suggest that variable activity of the renin-angiotensin system may contribute to inconsistencies in the association between insulin resistance and hypertension. PMID- 8349812 TI - Parathyroid hormone-like protein is a secretory product of atrial myocytes. AB - Parathyroid hormone-like protein (PLP) was originally identified from tumors associated with hypercalcemia. Recently, it has been found to be expressed in a stretch-responsive manner in several types of smooth muscle. We studied adult rat heart muscle for the presence of the PLP. Using immunohistology and the PCR, we demonstrated the presence of PLP and its mRNA in all heart chambers. Immunoelectron microscopy demonstrated PLP in secretory vesicles of atrial mycocytes. Using immunoassay, we demonstrated that atria contained a higher concentration of PLP than ventricles. Furthermore, primary cultures of both chambers released PLP into conditioned medium, with atria secreting more than ventricles. Considered with studies of the role of PLP in other tissues, our observations suggest that the production and secretion of PLP by cardiac myocytes represents a calcium-related regulatory function for this stretch-responsive polypeptide in the cardiovascular system. PLP in the heart may be the calcium counterpart for the atrial natriuretic-sodium regulatory axis of the cardiovascular system. PMID- 8349813 TI - Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro. AB - Human airway smooth muscle possesses an inhibitory nonadrenergic noncholinergic neural bronchodilator response mediated by nitric oxide (NO). In guinea pig trachea both endogenous NO and vasoactive intestinal peptide (VIP) modulate cholinergic neural contractile responses. To identify whether endogenous NO or VIP can modulate cholinergic contractile responses in human airways in vitro, we studied the effects of specific NO synthase inhibitors and the peptidase alpha chymotrypsin on contractile responses evoked by electrical field stimulation (EFS) at three airway levels. Endogenous NO, but not VIP, was shown to inhibit cholinergic contractile responses at all airway levels but this inhibition was predominantly in trachea and main bronchus and less marked in segmental and subsegmental bronchi. To elucidate the mechanism of this modulation we then studied the effects of endogenous NO on acetylcholine (ACh) release evoked by EFS from tracheal smooth muscle strips. We confirmed that release was neural in origin, frequency dependent, and that endogenous NO did not affect ACh release. These findings show that endogenous NO, but not VIP, evoked by EFS can inhibit cholinergic neural responses via functional antagonism of ACh at the airway smooth muscle and that the contribution of this modulation is less marked in lower airways. PMID- 8349815 TI - Structural changes underlying compensatory increase of diffusing capacity after left pneumonectomy in adult dogs. AB - To determine if the functional compensation in diffusing capacity of the remaining lung following pneumonectomy is due to structural growth, we performed morphometric analysis of the right lung in three adult foxhounds approximately 2 yr after left pneumonectomy (removal of 42% of lung) and compared the results to those in normal adult dogs previously studied by the same techniques. Diffusing capacity was calculated by an established morphometric model and compared to physiologic estimates at peak exercise in the same dogs after pneumonectomy. The major structural changes after left pneumonectomy are hyperinflation of the right lung, alveolar enlargement, and thinning of the alveolar-capillary tissue barrier. These changes confer significant functional compensation for gas exchange by reducing the overall resistance to O2 diffusion. The magnitude of compensation in diffusing capacity estimated either morphometrically or physiologically is similar. In spite of morphometric and physiologic evidence of functional compensation, there is no evidence of significant growth of structural components. After pneumonectomy, morphometric estimates of diffusing capacity are on average 23% higher than physiologic estimates in the same dogs at peak exercise. We conclude that the previously reported large differences between morphometric and physiologic estimates of diffusing capacity reflects the presence of large physiologic reserves available for recruitment. PMID- 8349814 TI - Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels. AB - The concentration of LDL in plasma is strongly influenced by the amount and the type of lipid in the diet. Recent studies in the hamster have shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liver. To investigate the mechanistic basis of this effect, rates of receptor-dependent LDL transport in the liver were correlated with LDL receptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fed safflower oil at all levels of cholesterol intake (26, 53, and 61% lower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). These fatty acid induced changes in hepatic LDL receptor activity were accompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level. PMID- 8349817 TI - Interleukin-8 and the neutrophil response to mucosal gram-negative infection. AB - Urinary tract infections activate a mucosal inflammatory response, which includes cytokine secretion and neutrophil influx. The mechanisms involved in the neutrophil influx have not been identified. Interleukin-8, a potent chemoattractant for neutrophils, is produced by urinary tract epithelial cell lines in vitro. This study analyzed the human IL-8 response to deliberate Escherichia coli infection of the urinary tract. Urine and serum samples were obtained before and after intravesical instillation of E. coli. Neutrophil numbers were determined on uncentrifuged urine, and IL-8 levels were measured by ELISA. A urinary IL-8 response was found in all patients after bacterial instillation, but no serum IL-8 was detected. There was a strong correlation between urinary IL-8 levels and urinary neutrophil numbers. The same E. coli strains used to colonize the patients stimulated IL-8 production in urinary tract epithelial cells. The level of IL-8 secreted by epithelial cell lines was influenced by the fimbrial properties of the E. coli. These results demonstrated that E. coli elicit a mucosal IL-8 response in humans, and suggested that IL-8 is involved in the onset of pyuria. Epithelial cells may be an important source of IL-8 during urinary tract infection. PMID- 8349818 TI - A molecular map of G protein alpha chains in microdissected rat nephron segments. AB - Membrane-associated guanine nucleotide binding proteins regulate many receptor mediated signals. Heterogeneity of biochemical and functional properties in nephron segments could be due to differences in G protein expression. To ascertain whether such heterogeneity of G proteins is present in various nephron segments, this study examines the distribution and relative abundance of G protein alpha chains in microdissected medullary thick ascending limb, cortical collecting tubules, outer medullary collecting tubules, proximal inner medullary tubules, and distal inner medullary tubules. Reverse transcription and polymerase chain reactions were employed using oligonucleotides encoding highly conserved regions of all known alpha chains. The cDNA was sequenced for alpha chain identification. The alpha i2 versus alpha s distribution was different in the outer medullary collecting tubules, when compared with the medullary thick ascending limb (P < 0.001) or the cortical collecting tubule, the proximal inner medullary tubules, and the distal inner medullary tubules (P < 0.05). These latter four segments did not significantly differ from each other. A similar analysis was applied to the frequently used line of kidney cells, LLC-PK1, whose exact cellular origin remains unclear. Interestingly, we detected both alpha i2 and alpha i3, while only alpha i2 was detected in the rat distal nephron. No alpha o or alpha z reverse transcription PCR products were detected. In contrast alpha 11 and alpha 14 members of the more recently described alpha q family were detected in the outer medullary collecting tubules and the proximal inner medullary tubules, respectively. We conclude that the majority of nephron segments have a relatively constant distribution of G protein alpha chains. PMID- 8349816 TI - Coincidence of genetic loci for plasma cholesterol levels and obesity in a multifactorial mouse model. AB - We have examined backcross progeny derived from a cross of Mus spretus with C57BL/6J, that range from 1 to 50% carcass lipid (n = 215), and from 22 to 130 mg/dl plasma total cholesterol (n = 238). Statistical analysis revealed that distal mouse chromosome 7 exhibits significant linkage both to plasma total cholesterol (likelihood of the odds [LOD] 5.8) and to carcass lipid (LOD 3.8). A locus on chromosome 6 also shows significant linkage to plasma total cholesterol (LOD 5.6), but no linkage to carcass lipid. Neither chromosomal region contains any previously mapped genes likely to influence lipoprotein metabolism, indicating that novel genetic factors contributing to plasma lipoprotein levels have been identified. PMID- 8349820 TI - V3-specific neutralizing antibodies in sera from HIV-1 gp160-immunized volunteers block virus fusion and act synergistically with human monoclonal antibody to the conformation-dependent CD4 binding site of gp120. NIH-NIAID AIDS Vaccine Clinical Trials Network. AB - Sera from 11 volunteers immunized with a recombinant HIV-1 gp160-expressing vaccinia virus (HIVAC-1e; Oncogen/Bristol-Myers Squibb, Seattle, WA) and boosted with baculovirus-derived rgp160 (VaxSyn; MicroGeneSys, Inc., Meriden, CT) were evaluated for functional serum antibodies and their epitopes. Sera obtained prior to boosting had undetectable HIV-1-specific IgG and neutralizing activity, and did not block HIV-1 from binding or fusing to CD4+ MT-2 cells. 14 d after boosting, sera from each volunteer contained HIV-1-specific IgG titers of 1:40 to 1:1,280. Five of these sera also contained neutralizing antibodies, where most or all neutralizing activity was blocked by a synthetic peptide corresponding to amino acids 307-330 of the V3 loop of gp120, indicating that neutralizing antibodies were mostly V3 loop-specific. All sera obtained after boosting contained HIV-1 binding/fusion-inhibition antibodies, and a significant portion of their activity was blocked by the V3 loop peptide, a result consistent with the presence of antibodies against the region of the V3 loop that participates in fusion. Three sera with V3 loop-specific neutralizing and fusion-inhibition antibodies were studied further. In competitive antibody binding experiments, antibodies reactive with the conformation-dependent, CD4 binding site of gp120 were undetectable in each serum. When evaluated in combination with a monoclonal antibody to the CD4 binding site of gp120, two sera demonstrated synergism in neutralizing assays, and all three sera demonstrated synergism in binding/fusion inhibition assays, further indicating that the functional antibodies were primarily V3 loop-specific. The synergism also suggests that a vaccine that elicits strong serum antibody responses to both regions of gp120 may improve the potential for inducing protective immunity. PMID- 8349819 TI - The human 230-kD bullous pemphigoid antigen gene (BPAG1). Exon-intron organization and identification of regulatory tissue specific elements in the promoter region. AB - The 230-kD bullous pemphigoid antigen (BPAG1), a hemidesmosomal protein, is encoded by a gene at the human chromosomal locus 6p11-12. We have elucidated the exon-intron organization of the entire human BPAG1 gene, including approximately 2.6 kb of 5'-flanking DNA. Seven overlapping genomic clones, spanning approximately 20 kb, contained the entire approximately 9 kb coding sequence of BPAG1 and consisted of 22 separate exons, which varied from 78 to 2,810 bp in size. The 5' flanking region of DNA, upstream from the ATG initiation codon for translation, was found to contain several putative transcriptional response elements. Most interestingly, two motifs potentially conferring keratinocyte specific expression to the gene were detected. The presence of such elements was suggested by approximately 20-fold higher expression of a promoter/chloramphenicol acetyl transferase (CAT) construct in normal human epidermal keratinocytes that express the endogenous gene, as compared to several non-expressing cell types. Transient transfections with 5'-deletion clones of the promoter/reporter gene (CAT) constructs identified a region containing a putative tissue specific element, KRE2, which also conferred tissue specificity to the expression of the truncated promoter downstream from this element, however, a mutated derivative of KRE2 was not functional. Detailed knowledge of the structure and regulation of the BPAG1 gene will aid in further elucidation of diseases affecting the cutaneous basement membrane zone. PMID- 8349821 TI - Deficiency of dystrophin-associated proteins in Duchenne muscular dystrophy patients lacking COOH-terminal domains of dystrophin. AB - Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a cytoskeletal protein tightly associated with a large oligomeric complex of sarcolemmal glycoproteins including dystroglycan, which provides a linkage to the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins, causing the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix which, in turn, may render muscle cells susceptible to necrosis. The COOH-terminal domains (cysteine-rich and carboxyl-terminal) of dystrophin have been suggested to interact with the sarcolemmal glycoprotein complex. However, truncated dystrophin lacking these domains was reported to be localized to the sarcolemma in four DMD patients recently. Here we report that all of the dystrophin-associated proteins are drastically reduced in the sarcolemma of three DMD patients in whom dystrophin lacking the COOH-terminal domains was properly localized to the sarcolemma. Our results indicate that the COOH-terminal domains of dystrophin are required for the proper interaction of dystrophin with the dystrophin-associated proteins and also support our hypothesis that the loss of the dystrophin-associated proteins in the sarcolemma leads to severe muscular dystrophy even when truncated dystrophin is present in the subsarcolemmal cytoskeleton. PMID- 8349822 TI - Small elevations of glucose concentration redirect and amplify the synthesis of guanosine 5'-triphosphate in rat islets. AB - Recent studies suggest a permissive requirement for guanosine 5'-triphosphate (GTP) in insulin release, based on the use of GTP synthesis inhibitors (such as myocophenolic acid) acting at inosine monophosphate (IMP) dehydrogenase; herein, we examine the glucose dependency of GTP synthesis. Mycophenolic acid inhibited insulin secretion equally well after islet culture at 7.8 or 11.1 mM glucose (51% inhibition) but its effect was dramatically attenuated when provided at < or = 6.4 mM glucose (13% inhibition; P < 0.001). These observations were explicable by a stimulation of islet GTP synthesis derived from IMP since, at high glucose: (a) total GTP content was augmented; (b) a greater decrement in GTP (1.75 vs. 1.05 pmol/islet) was induced by mycophenolic acid; and (c) a smaller "pool" of residual GTP persisted after drug treatment. Glucose also accelerated GTP synthesis from exogenous guanine ("salvage" pathway) and increased content of a pyrimidine, uridine 5'-triphosphate (UTP), suggesting that glucose augments production of a common regulatory intermediate (probably 5-phosphoribosyl-1 pyrophosphate). Pathway-specific radiolabeling studies confirmed that glucose tripled both salvage and de novo synthesis of nucleotides. We conclude that steep changes in the biosynthesis of cytosolic pools of GTP occur at modest changes in glucose concentrations, a finding which may have relevance to the adaptive (patho) physiologic responses of islets to changes in ambient glucose levels. PMID- 8349823 TI - Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. AB - We employed homologous recombination in embryonic stem cells to produce mice lacking functional LDL receptor genes. Homozygous male and female mice lacking LDL receptors (LDLR-/- mice) were viable and fertile. Total plasma cholesterol levels were twofold higher than those of wild-type litter-mates, owing to a seven to ninefold increase in intermediate density lipoproteins (IDL) and LDL without a significant change in HDL. Plasma triglyceride levels were normal. The half lives for intravenously administered 125I-VLDL and 125I-LDL were prolonged by 30 fold and 2.5-fold, respectively, but the clearance of 125I-HDL was normal in the LDLR-/- mice. Unlike wild-type mice, LDLR-/- mice responded to moderate amounts of dietary cholesterol (0.2% cholesterol/10% coconut oil) with a major increase in the cholesterol content of IDL and LDL particles. The elevated IDL/LDL level of LDLR-/- mice was reduced to normal 4 d after the intravenous injection of a recombinant replication-defective adenovirus encoding the human LDL receptor driven by the cytomegalovirus promoter. The virus restored expression of LDL receptor protein in the liver and increased the clearance of 125I-VLDL. We conclude that the LDL receptor is responsible in part for the low levels of VLDL, IDL, and LDL in wild-type mice and that adenovirus-encoded LDL receptors can acutely reverse the hypercholesterolemic effects of LDL receptor deficiency. PMID- 8349824 TI - Dominant negative mutations of the scavenger receptor. Native receptor inactivation by expression of truncated variants. AB - The bovine scavenger receptor was truncated at amino acid 266 or 310 to delete either all or part, respectively, of the collagen-like domain. The truncated receptors were inactive in the binding and internalization of acetyl (Ac) low density lipoprotein (LDL). Coexpression of truncated receptor with the native receptor dramatically reduced the percentage of cells internalizing fluorescently labeled Ac LDL, compared with cells expressing the native receptor alone. The mutant truncated at amino acid 266 was most effective in receptor inactivation, resulting in a 42% or 80% decrease in the percentage of cells expressing active receptor when transfected in a 1:1 or 1:2 molar ratio (native:mutant), respectively, with native receptor. Degradation of 125I-Ac LDL was reduced up to 90% when the native and truncated mutant receptors were coexpressed. Scavenger receptor inhibition was specific because the activity of the LDL receptor was not altered. Transient transfection of the mouse macrophage cell line P388D1 with truncated scavenger receptor resulted in a 65% decrease in the uptake and degradation of Ac LDL but did not decrease the degradation of beta-migrating very low density lipoprotein, which is LDL receptor-mediated. These results demonstrate that expression of truncated bovine scavenger receptor inactivates both the native bovine and murine scavenger receptors, producing a dominant negative phenotype in vitro. PMID- 8349825 TI - Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects. AB - We measured biliary and fecal sterol outputs in 12 human subjects on a metabolic ward in four randomly allocated, 6-7 wk periods: (a) lovastatin (40 mg b.i.d.) + low cholesterol diet (mean 246 mg/d), (b) lovastatin + high cholesterol diet (mean 1,071 mg/d), (c) low cholesterol diet alone, (d) high cholesterol diet alone. In addition to lowering serum LDL cholesterol, lovastatin significantly lowered biliary secretion of cholesterol, fecal output of endogenous neutral sterols, cholesterol balance, and systemic cholesterol input (the sum of cholesterol synthesis and absorbed dietary cholesterol). The high cholesterol diet significantly lowered cholesterol balance, but significantly increased systemic cholesterol input and fecal output of acidic sterols. There was no significant interaction between lovastatin and dietary cholesterol for any parameter measured. Judging from these data, the primary action of lovastatin is to lower cholesterol synthesis and systemic cholesterol input, the main compensatory response being reduced biliary cholesterol secretion. Conversely, increased dietary cholesterol appears to increase systemic cholesterol input, the major compensatory response being increased bile acid synthesis. There appears to be no interaction between these two perturbations of systemic cholesterol input. PMID- 8349826 TI - 39-kD protein inhibits tissue-type plasminogen activator clearance in vivo. AB - Tissue-type plasminogen activator (t-PA) is a plasma serine protease that catalyzes the initial and rate-limiting step in the fibrinolytic cascade. t-PA is widely used as a thrombolytic agent in the treatment of acute myocardial infarction. However, its use has been impaired by its rapid hepatic clearance from the circulation following intravenous administration. Studies with both rat hepatoma MH1C1 cells (G. Bu, S. Williams, D. K. Strickland, and A. L. Schwartz, 1992. Proc. Natl. Acad. Sci. USA. 89:7427-7431) and human hepatoma HepG2 cells (G. Bu, E. A. Maksymovitch, and A. L. Schwartz. 1993. J. Biol. Chem. 28:13002 13009) have shown that binding of t-PA to its clearance receptor, the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor, is inhibited by a 39-kD protein that copurifies with this receptor. Herein we investigated whether administration of purified recombinant 39-kD protein would alter t-PA clearance in vivo. We found that intravenous administration of purified 39-kD protein to rats prolonged the plasma half-life of 125I-t-PA from 1 min to approximately 5-6 min. The plasma half-life of t-PA enzymatic activity was similarly prolonged following intravenous administration of purified 39-kD protein. In addition we found that the 39-kD protein itself was rapidly cleared from the circulation in vivo. Clearance of 125I-39-kD protein was a biphasic process with half-lives of 30 s and 9 min and the liver was the primary organ of clearance. Preadministration of excess unlabeled 39-kD protein slowed 125I-39-kD protein clearance in rats in a dose-dependent manner, suggesting that specific clearance receptors were responsible for this process. Administration of increasing doses of unlabeled 39-kD protein along with labeled 39-kD protein resulted in a decrease in the amount of labeled 39-kD protein associating with the liver and a concomitant increase in the amount of labeled 39-kD protein associating with the kidneys, indicating two clearance mechanisms exist for the 39-kD protein. PMID- 8349827 TI - Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) mucin is expressed by lactating mammary gland epithelial cells and is present in milk. AB - Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) is a mucinlike endothelial glycoprotein that acts as an adhesive ligand for L selectin by presenting one or more O-linked carbohydrates to the lectin domain of this leukocyte cell surface selectin. The GlyCAM 1 glycoprotein has been previously shown to be expressed specifically by the endothelial cells of peripheral and mesenteric lymph nodes and in an unknown site in lung. Here we report that this protein is also expressed during lactation by mammary epithelial cells. Northern blot analysis has shown that the mRNA for GlyCAM 1 appears to be induced during pregnancy in a manner similar to that previously described for hormonally induced milk proteins. In situ hybridization analysis reveals that the site of GlyCAM 1 synthesis in the mammary gland is in the epithelial cells that produce these same milk proteins. Immunohistochemistry of mammary glands using antisera directed against GlyCAM 1 peptides demonstrates that these epithelial cells contain GlyCAM 1 protein, and that this protein is also found lumenally in the milk of the secreting mammary gland. Analysis of murine milk shows that immunoreactive GlyCAM 1 is found in the soluble whey fraction. Finally, labeling analysis of milk GlyCAM 1 has demonstrated that this form of the glycoprotein lacks the sulfate modified carbohydrate that has recently been shown to be required for the ligand binding activity to L selectin. The nonsulfated mammary GlyCAM 1 is unable to interact with L selectin, consistent with the hypothesis that milk GlyCAM 1 has a different function than endothelial GlyCAM 1. These data thus suggest that milk GlyCAM 1 is a hormonally regulated milk protein that is part of the milk mucin complex. In addition, the finding that the mammary form of GlyCAM 1 contains different carbohydrate modifications than the endothelial form suggests that this glycoprotein may be a scaffold for carbohydrates that mediate functions in addition to cell adhesion. PMID- 8349828 TI - Immunochemical and molecular characterization of anti-RNA polymerase I autoantibodies produced by tight skin mouse. AB - Autoantibodies against nuclear proteins like RNA polymerase I (RNA pol I) are produced in a number of rheumatic autoimmune diseases. Production of antibodies specific for the 190-kD subunit of RNA pol I appears to be characteristic in the patients with systemic sclerosis. Previous investigations have shown that the tight skin (TSK) mouse is an experimental model for systemic sclerosis. In the present study we show that the TSK mice produce high titers of anti-RNA pol I antibodies, both of IgM and IgG classes. To characterize the immunochemical properties of these antibodies we obtained a large panel of hybridomas from these mice. Analysis of these hybridomas revealed that clonal frequency of autoreactive B cells specific for RNA pol I are higher in the TSK mice that in the controls. mAbs obtained from the TSK mice were specific for the 190-kD subunit and cross reacted with Escherichia coli and phage T7 RNA polymerases (155-, 150-, and 107 kD polypeptides). We have also demonstrated that these antibodies bind better to the phosphorylated enzymes. The anti-RNA pol I mAbs were divided into three groups in terms of their functional property. The first group of antibodies increased the catalytic activity of the enzyme whereas the antibodies of the second group inhibited the enzymatic activity. Competitive inhibition RIAs showed that these two groups of antibodies bound to distinct epitopes. The third group of antibodies was neutral and had no activity on the enzyme function. These results suggest that TSK mouse anti-RNA pol I antibodies recognize three or more conserved epitopes. To understand the molecular basis of the generation of such autoreactive antibodies we analyzed their V gene repertoire. Northern analysis of RNAs of 14 TSK hybridomas showed that the VH genes encoding these antibodies were mainly from VH J558 family. It is possible that these genes were derived from a single germline gene or from a set of related genes of a single subgroup. PMID- 8349830 TI - Assessment of pain in cervical dentinal sensitivity studies. A review. AB - Traditionally cervical dentinal sensitivity (CDS) has been evaluated mainly subjectively on the basis of the individual patient's subjective response, e.g., in the form of verbal rating and visual analogue scales and questionnaires. The stimuli used for evaluating this response can be grouped into 4 main categories: mechanical, chemical, electrical and thermal. This review of the literature, however, indicates that there are problems in evaluating patient subjective response to these various test stimuli used in the assessment and treatment of CDS. Opinions also vary as to the reliability of some of these methods of assessment, although recently, efforts have been made to develop controlled reproducible stimuli more suited to the evaluation of CDS. Currently no single method of eliciting and assessing CDS may be considered ideal. Further research is required to evaluate suitable methodology for the quantification of realistic test stimuli under controlled clinical conditions, whereby the subjective response may be objectively measured by the investigator. PMID- 8349829 TI - Bioenergetic abnormalities associated with severe left ventricular hypertrophy. AB - Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia. PMID- 8349831 TI - Suppression of subgingival Actinobacillus actinomycetemcomitans in localized juvenile periodontitis by systemic tetracycline. AB - The current study assessed the clinical and microbiological effects of systemic antimicrobial therapy alone in Actinobacillus actinomycetemcomitans-infected adolescents with periodontal disease. The study involved 6 localized juvenile periodontitis patients 13-18 years of age, who harbored high numbers of A. actinomycetemcomitans in subgingival plaque samples. The periodontal lesions were microbiologically monitored by selective culture, and clinically assessed for probing pocket depth and periodontal attachment level 3 months prior to baseline, and at 3, 6, 12, and 24 months posttreatment. Tetracycline-HCl (250 mg/QID) was prescribed until 1 week after subgingival A. actinomycetemcomitans was no longer detectable or for a maximum of 8 weeks. During 3 months prior to treatment, pocket depth was unchanged, and was then significantly reduced from an average of 7.1 mm to 5.1 mm 12 months after treatment (p = 0.02). The mean change in clinical attachment level was a gain of 1.4 mm between baseline and 12 months (p = 0.02). 3 of the 6 patients were still infected with A. actinomycetemcomitans after 8 weeks of antibiotic therapy and 4 subjects were infected at 12 months. Numbers of A. actinomycetemcomitans were still suppressed in most lesions. There was a strong association between mean numbers of A. actinomycetemcomitans in periodontal pockets and mean change in probing attachment level at any given time point. For 22 available comparisons, derived from all time points, there was a strong association (r = 0.68) between subgingival A. actinomycetemcomitans and change in probing attachment level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349832 TI - The periodontally-involved root surface. AB - Recent years have seen much research on the periodontally-involved root surface. Many of these studies have produced results which suggest that plaque contaminants of the root surface are only superficially placed, and capable of being removed by gentle means. Further research has attested to the difficulties in rendering periodontally-involved root surfaces free of calculus deposits by instrumentation, yet clinical studies show that periodontal disease can be managed by root planing. It is concluded that root surface debridement is best assessed on the basis of the healing response and that it should aim to disrupt plaque on and remove plaque from the periodontally-involved root surface rather than to remove part of the root surface itself. PMID- 8349833 TI - Treatment of periodontal furcation defects. Coronally positioned flap with or without citric acid root conditioning in class II defects. AB - A total of 27 mandibular, buccal class II furcation defects were treated in 16 subjects using a coronally positioned flap procedure, with or without citric acid conditioning of the root surfaces. The effect of the therapies was evaluated from a series of soft and hard tissue measurements. Mean improvements were slightly greater for acid treated than for non-acid treated defects. However, none of the mean differences reached statistical significance, indicating that citric acid conditioning may not be a necessary part of the regenerative, coronally positioned flap procedure in mandibular furcations. PMID- 8349835 TI - Periodontal attachment loss assessed by linear and area measurements in vitro. AB - The aim of the present study was to investigate the relationship between linear and area measurements of periodontal attachment loss, and to determine the root surface area on different tooth-types. Extracted permanent teeth were collected in a national survey including a systematic random sample of 500 Norwegian dentists. The response rate was 70%. Altogether 329 teeth were received, 81 of them (excluding 3rd molars) were subjected to both linear and area measurements of attachment loss. Using a dissecting microscope (10 x), 4 to 8 duplicate linear measurements were recorded per tooth. The areas of both lost and remaining periodontal attachment were measured by a method based on controlled release of Cu and Co metal ions from coatings applied to the root surface. Linear loss of attachment for single-rooted teeth (n = 63) was mean = 44.0% and the area loss mean = 49.2%. The corresponding measurements for multi-rooted teeth (n = 18) were mean = 30.3% and mean = 35.1%, respectively. The correlation between linear and area loss was r = 0.78 for single-rooted and r = 0.75 for multi-rooted teeth (p < 0.01). The lower correlation in multi-rooted teeth is probably due to the more complex root anatomy. It is concluded that there is a strong correlation between linear loss of attachment and area of periodontal support lost for teeth with early to moderate loss of attachment, and that linear measurements tend to underestimate the remaining periodontal attachment. PMID- 8349834 TI - Long-term control of diabetes mellitus and periodontitis. AB - The purpose of this study was to evaluate the association between long-term control of diabetes mellitus (DM) and periodontitis. A total of 75 diabetics (Type I or II) aged 20-70 years with long-term records of their diabetic control were selected for the study. The following periodontal variables were recorded in a randomized half-mouth examination: plaque, calculus (+/-), probing depth (pd) and attachment loss (al). The mean of glycosylated hemoglobin measurements (HbAlc) over the past 2-5 years was used to indicate the long-term control of DM. The study participants were divided into well-, moderately- and poorly-controlled diabetics. An increase in the prevalence, severity and extent of periodontitis with poorer control of diabetes was observed. The extent of calculus also increased with poorer control. In a multiple regression analysis, calculus and long-term control of diabetes were significant variables when pd > or = 4 mm was used as the dependent variable. Age was a significant predictor for al > or = 3 mm but not for pd > or = 4 mm. Sex, duration and type of DM were not significant variables in the regression models. Less than 2% of sites with no calculus demonstrated pd > or = 4 mm. When calculus was present, the frequency of pd > or = 4 mm increased from 6% in the well-controlled diabetics to 16% in the poorly controlled ones. We conclude that periodontitis in diabetics is associated with long-term metabolic control and presence of calculus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349836 TI - The immediate effects of smoking on gingival fluid flow. AB - The aim of the present study was to examine the immediate effect of smoking a cigarette on gingival crevice fluid (GCF) flow-rate. The study involved 17 healthy volunteers (6 male, 11 female) aged 19-57 years (mean 34.5 years) who regularly smoked cigarettes. All were periodontally healthy. GCF was collected at the mesio-buccal aspects of the right and left maxillary 2nd premolar teeth, using filter-paper strips left in place for 3 min. Samples were taken at baseline and subsequently at 10 min intervals for 70 min. Each subject sham smoked an unlit standard cigarette for 7 min after the 20 min recording, and smoked the same cigarette for 7 min to within 1 cm of the filter, following the 40 min recording. The results showed that following sham smoking (30 min recording) GCF volume increased by a mean of 16.7% (p = 0.057), and following smoking (50 min recording) GCF volume increased by a mean of 89.7%, over the previous recording (p < 0.0001). The increase following smoking was greater than that following sham smoking (p < 0.0001). Flow-rate returned to near resting levels within the experimental period. The results indicate that smoking produces a marked transient increase in GCF flow-rate, which might reflect changes in blood flow known to be produced by nicotine. PMID- 8349837 TI - A skin window study of neutrophil migration in subjects with localized juvenile periodontitis. AB - This study investigated the effect of a chemoattractant, N-formyl-methionyl leucyl-phenylalanine (FMLP), upon skin window migration of neutrophils into filters in 5 patients with a history of localized juvenile periodontitis (LJP) and 8 controls. On 2 occasions, each subject had 2 superficial skin abrasions made on the inner aspect of the forearm. Initial periodontal treatment was carried out on the disease group between the visits. On one skin window filters were placed that were soaked in physiological saline, and on the other filters soaked with FMLP. Leading fronts and cell densities were measured in each filter. At visit 1, LJP subjects had significantly lower leading fronts and cell densities. At visit 2, the differences were insignificant. The leading fronts for the LJP group were significantly improved on the second visit. No difference was observed between saline and FMLP. The findings of this study indicate that neutrophil migration is reduced in LJP patients where treatment is not involved, and that FMLP has no effect on neutrophil migration from the skin windows under the conditions of this study. PMID- 8349838 TI - The use of topical flurbiprofen as an adjunct to non-surgical management of periodontal disease. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) have been used as systemic and topical preparations to control chronic periodontal disease in both animal and clinical human trials. Equivocal findings have failed to confirm whether any one NSAID is particularly efficacious, although flurbiprofen appears to be one of the most promising. 49 patients were allocated at baseline to test (25) and control (24) groups in a 12-month, controlled clinical trial. The groups were of similar age and sex distributions. During the first 3 months, both groups were given oral hygiene instruction and received scaling and root planning. The test patients were prescribed a 1% w/w flurbiprofen toothpaste to use 2 x daily for the entire 12 months. Control subjects were prescribed a placebo dentifrice. Plaque scores, bleeding scores, crevicular fluid flow, probing pocket depths and attachment levels were assessed at baseline and at 3, 6, 9 and 12 months. Radiographs were taken at baseline and 12 months using a modified intraoral, repositionable film holder. Both the flurbiprofen and placebo showed significant improvements in the clinical parameters over 12 months and there were no significant differences between the groups. Flurbiprofen-treated patients however, demonstrated a significantly greater proportion of sites (8.0%) with bone gain when compared to the placebo group (3.3%). There were no significant differences between the groups in the number of sites showing bone loss or no change. It is concluded that the 1% w/w flurbiprofen toothpaste exerts a small, yet significant effect on bone metabolism in the absence of any apparent effects on clinical parameters. PMID- 8349839 TI - Evaluation of peri-implant sulcular temperature. AB - Sulcular temperatures were measured on 35 clinically stable and restored osseointegrated dental implants and compared to 50 remaining natural teeth in 9 partially-edentulous adults using the PerioTemp temperature probe (ABIO-DENT, Inc., Danvers, MA USA). Replicate peri-implant sulcular measurements showed a mean difference of 0.1 +/- 0.15 (SD) degrees C. Implant temperatures varied from 0.41 to 3.9 degrees C below sublingual temperatures measured on each patient, and maxillary implants were significantly cooler than mandibular implants (p < 0.001, t-test). A posterior-to-anterior temperature gradient was found in both the maxilla and mandible, with anterior implants significantly cooler than posterior fixtures. No significant differences were found in sulcular temperatures of osseointegrated dental implants and natural teeth located in anatomically equivalent oral sites. Similarly to natural teeth, sulcular temperature may serve as a valuable diagnostic tool in evaluating dental implant status. PMID- 8349840 TI - Immunocytochemical staining of AII-amacrine cells in the rat retina with antibodies against parvalbumin. AB - The rod dominated rodent retina is the preferred tissue for in vitro studies of mammalian retinal physiology and pharmacology. The rod pathway through the rat retina was investigated, therefore, in order to find out whether its organization follows the mammalian "plan." AII-amacrine cells of the rat retina were injected with Lucifer Yellow to characterize the morphology of this bistratified interneuron of the rod pathway. When sections or whole mounts of the rat retina were stained with antibodies against the calcium binding protein parvalbumin (PV), two different amacrine cell types were labeled: the AII-amacrine cell and a widefield amacrine cell. They occur at a ratio of 12:1. Weak label was also observed in ganglion cells. The density of PV-labeled AII-cells decreases from approximately 7,000 cells/mm2 in upper central retina to 2,000 cells/mm2 in peripheral retina. Their cell bodies form a regular mosaic, and the dendritic arbors of three neighbouring AII-amacrine cells overlap (coverage of 3). PMID- 8349842 TI - Contact-spacing among astrocytes is independent of neighbouring structures: in vivo and in vitro evidence. AB - We have examined the morphology of astrocytes and the arrays they form in two situations, in retinas from which ganglion cells and blood vessels have been caused to degenerate, and in vitro. These observations were made to test whether the regularity of the spacing of astrocytes within normal central nervous tissue results from interaction among astrocytes, or from interaction between astrocytes and other elements of that tissue. Both in the partially degenerated cat retina, and in cultures of astrocytes from neonatal rat cortex, astrocytes make and maintain contact with neighbouring astrocytes, yet space their somas apart, giving regularity to the arrays. These results support the hypothesis that the regularity observed in arrays of astrocytes in intact tissue results from an interaction among astrocytes, independent of neighbouring structures, and lead us to suggest that the cell-cell interactions involved in contact spacing serve to distribute astrocytes through the central nervous system, and may, in other tissues, underlie the formation of epithelia. PMID- 8349841 TI - Electron microscopic analysis of the rod pathway of the rat retina. AB - Two immunocytochemical markers were used to label the rod pathway of the rat retina. Rod bipolar cells were stained with antibodies against protein kinase C and AII-amacrine cells with antibodies against parvalbumin. The synaptic circuitry of rod bipolars in the inner plexiform layer (IPL) was studied. Rod bipolar cells make approximately 15 ribbon synapses (dyads) in the IPL. Both postsynaptic members of the dyads are amacrine cells; one is usually the process of an AII-amacrine cell and the other one frequently provides a reciprocal synapse. No direct output from rod bipolar cells into ganglion cells was found. AII-amacrine cells make chemical output synapses with cone bipolar cells and ganglion cells in sublamina a of the IPL. They make gap junctions with cone bipolar cells and other AII-amacrine cells in sublamina b of the IPL. The rod pathway of the rat retina is practically identical to that of the cat and of the rabbit retina. It is very likely that this circuitry is a general feature of mammalian retinal organization. PMID- 8349843 TI - Immunoelectron microscopic analysis of a novel carbohydrate differentiation antigen (CDA-3C2) in the developing rat olfactory and otic systems. AB - A carbohydrate differentiation antigen (CDA-3C2) exhibits a highly specific and restricted pattern of expression during rat embryogenesis. In the periphery of the embryo, this antigen is associated transiently with the lateral ectoderm but is retained only in the olfactory and otic epithelium throughout morphogenesis. At the light microscopic level, CDA-3C2 immunoreactivity appears mostly along cell periphery and in the extracellular matrix. The aim of the present study was to determine the specific cellular and subcellular distribution of CDA-3C2 in vivo in order to identify potential sites of cellular and tissue function of the antigen during embryogenesis. There was a strikingly similar subcellular distribution of CDA-3C2 in the developing otic and olfactory systems, found mostly along cell membranes, microvillar projections and acellular secretions of the epithelium. Mature sensory components of the epithelia were not immunoreactive, whereas supportive cells and their secreted structures were densely stained. The highly coincident nature of CDA-3C2 in both sensory epithelia suggests that this carbohydrate epitope, and possibly its carrier macromolecule, participate in a morphogenetic function common to these two sensory epithelia. PMID- 8349844 TI - Developmental plasticity in cerebellar tactile maps: fractured maps retain a fractured organization. AB - Plasticity following deafferentation has been repeatedly demonstrated in topographic sensory maps in the mammalian brain. In this paper we investigated the developmental plasticity of the fractured somatotopic map found in the tactile regions of the rat cerebellum. At various stages of postnatal development between postnatal days 1 and 30, we cauterized the infraorbital branch of the trigeminal nerve, which innervates the upper lip, furry buccal pad, and vibrissae that are represented within cerebellar folium crus IIa. The organization of the crus IIa map was then examined 2 to 3 months after denervation. We found that tactile receptive fields had reorganized throughout the denervated area but maintained a fractured somatotopy. Comparison of the reorganization in different animals showed that the denervated upper lip region was consistently and predominantly replaced by representation of the upper incisors. Analysis of evoked field potentials revealed an alteration, in denervated animals, of the response of the granule cell layer to brief tactile stimulation. This response in normal animals consists of two components at different latencies. Animals lesioned later in development were less likely to have the short latency component. This result suggests a difference in the developmental sensitivity of different cerebellum-related pathways to nerve lesions. PMID- 8349846 TI - Sequential differentiation of sensory innervation in the mystacial pad of the ferret. AB - The mystacial pad of the ferret has an elaborate sensory innervation provided by three types of terminal nerves that arise from the infraorbital branch of the trigeminal nerve. Deep and superficial vibrissal nerves innervate nearly exclusive targets in the large follicle-sinus complexes (F-SCs) at the base of each tactile vibrissa. Dermal plexus nerves innervate the fur between the vibrissae. Each type of nerve provides a similar variety of sensory endings, albeit to different targets. In this study, Winkelmann and Sevier-Munger reduced silver techniques revealed that most of the endings differentiate postnatally in an overlapping sequence like that observed previously in the rat. Afferents from the deep vibrissal nerves begin to differentiate first, followed successively by those from superficial vibrissal nerves and the dermal plexus. Within each type of nerve, Merkel endings begin to differentiate first, followed successively by lanceolate endings and circumferential endings. In the ferret, the differentiation of the intervibrissal fur and its innervation is slightly delayed but substantially overlaps the development of the vibrissal innervation, whereas in the rat it occurs almost entirely later. There was no evidence of a transient exuberant or misplaced innervation or other secondary remodeling. Differentiating afferents and endings are located only in the sites normally seen in the adult, suggesting a high degree of afferent-target specificity. In the ferret, innervation is virtually lacking in one target--the inner conical body of the F SCs, which is densely innervated in the rat. This lack was due to a failure of innervation to develop rather than to a secondary elimination of a transient innervation. PMID- 8349845 TI - Spatial distributions of chemically identified intrinsic neurons in relation to patch and matrix compartments of rat neostriatum. AB - The spatial distributions and dendritic branching patterns of chemically identified subpopulations of striatal intrinsic neurons, defined by immunoreactivity for choline acetyltransferase (ChAT), neuropeptide Y or parvalbumin, were studied in relation to patch and matrix compartments of rat neostriatum. ChAT-immunoreactive cells and fibers showed an uneven pattern of distribution in the striatum. ChAT immunoreactivity was higher in the dorsolateral part and lower in the ventromedial part of the striatum. This regional gradient pattern is the inverse of the overall pattern of calbindin D28k immunoreactivity. However, in small regions close to the lateral ventricle and globus pallidus, areas containing fewer ChAT-immunoreactive cells and fibers coincided with those containing low calbindin D28k immunoreactivity. Neuropeptide Y immunoreactivity was uniform in the neostriatum. Certain neuropeptide Y cells (about 20%) were also immunoreactive for calbindin D28k, indicating that at least a small population of calbindin D28k-immunoreactive cells are medium aspiny cells. Parvalbumin immunoreactivity was not uniform in the striatum. A higher density of parvalbumin immunoreactivity was found in the neuropil in lateral and caudal parts than in the medial part. Small regions with weaker parvalbumin immunoreactive neuropil partially corresponded to calbindin D28k poor patches. Larger cells immunoreactive for parvalbumin were preferentially located in lateral and caudal parts of the striatum. Cells immunoreactive for ChAT, neuropeptide Y or parvalbumin showed basically similar distribution patterns in relation to the patch and matrix compartments. Most stained cells were located in the matrix, but some were located at the borders of patches and a few were inside patches. Most primary dendrites of stained cells in the matrix or patches remained confined to these compartments, but cells on the borders invariably extended dendrites into both compartments. The striatal intrinsic neurons form chemically differentiated neuronal circuits within the matrix, and the patches and those whose dendrites cross the borders may contribute to associational interconnections between the two compartments, unlike the spiny projection neurons whose dendrites are confined to one or the other compartment. PMID- 8349847 TI - Distribution of transitory corpus callosum axons projecting to developing cat visual cortex revealed by DiI. AB - Functional studies of the development of the corpus callosum in the cat have shown that an intact callosum during postnatal month 1 is necessary for normal visual development. In vivo tracing techniques have not provided enough information on corpus callosum connectivity to fully evaluate the evidence for a morphological mechanism for the functional effects of neonatal callosum section. However, lipophilic in vitro membrane tracers permit a more detailed search for such evidence because the entire limit of many cells can be labeled simultaneously. To investigate the morphological basis for the observed functional results in cats, the corpus callosum was labeled in vitro with the carbocyanine dye, DiI. Crystals of DiI were placed in the midsagittal callosum in tissue from 2 to 277-day-old cats. Tissue was coronally sectioned 3-22 months later. Sections were photographed and reconstructed to show the overall distribution of corpus callosum projections, as well as the locations of individual corpus callosum axons and their presumed terminals. The distribution of corpus callosum projections, examined in cortical areas 17-19, 7, and posterior medial lateral suprasylvian cortex, changes significantly during development. During postnatal week 1, callosal axons extend throughout these cortical areas to layer I. Numerous varicosities on callosal axons are located en passant and at axon terminals in layer I. During postnatal week 2, the density of callosal projections is reduced in all cortical areas, although many axons still extend to layer I. By postnatal month 2, the callosal axons extending to layer I are predominantly near the border with adjacent cortical areas; in the nonborder regions of these areas, many axons extend to layer VI while a much smaller number of axons extend to layers II-V. By postnatal month 3, the callosal projections to supragranular layers are almost exclusively restricted to cytoarchitectonic border regions; in the remaining regions, including medial area 17, there are occasional axons extending to the supragranular layers and only a moderate number of axons extending to infragranular layers. Thus, a substantial number of elaborately formed transitory corpus callosum axons, distributed throughout visual cortex, exist for several weeks during postnatal development; in area 17, these axons are found in central through peripheral visual field representations. The transitory callosal axons appear to have axon terminals in layer I as well as en passant terminals while extending through layers II-VI. If some of these terminals were to form synapses, there would be extensive opportunities for the corpus callosum to provide input to layers I-VI throughout visual cortex during the period of development in which cortical microcircuitry is being established. PMID- 8349848 TI - Organization and synaptic connections of cholinergic fibers in the cat superior colliculus. AB - The cat superior colliculus (SC) receives a dense cholinergic input from three brainstem nuclei, the pedunculopontine tegmental nucleus, the lateral dorsal tegmental nucleus, and the parabigeminal nucleus (PBG). The tegmental inputs project densely to the intermediate gray layer (IGL) and sparsely to the superficial layers. The PBG input probably projects only to the superficial layers. In the present study, the morphology of choline acetyltransferase (ChAT) immunoreactive axons and synaptic endings in the superficial and deep layers of the SC was examined by light and electron microscopy to determine whether these cholinergic afferents form different types of synapses in the superficial and deep layers. Two types of fibers were found within the zonal (ZL) and upper superficial gray layers (SGL): small diameter fibers with few varicosities and larger diameter fibers with numerous varicosities. Quantitative analysis demonstrated a bimodal distribution of axon diameters, with one peak at approximately 0.3-0.5 micron and the other at 0.9-1.0 micron. On the other hand, ChAT-immunoreactive fibers in the IGL were almost all small and formed discrete patches within the IGL. Two types of ChAT-immunoreactive synaptic profiles were observed within the ZL and upper SGL using the electron microscope. The first type consisted of small terminals containing predominantly round synaptic vesicles and forming asymmetric synaptic contacts, mostly on dendrites. The second type was comprised of varicose profiles that also contained round synaptic vesicles. Their synaptic contacts were always symmetric in profile. ChAT immunoreactive terminals in the IGL patches contained round or pleomorphic synaptic vesicles, and the postsynaptic densities varied from symmetric to asymmetric, including intermediate forms. However, no large varicose profiles were observed. This study suggests that cholinergic fibers include at least two different synaptic morphologies: small terminals with asymmetric thickenings and large varicose profiles with symmetric terminals. The large varicose profile in the superficial layers is absent in the IGL. This result suggests that the cholinergic inputs that innervate the superficial layers and the patches in the IGL of the cat SC differ in their synaptic organization and possibly also in their physiological actions. PMID- 8349849 TI - Quantitative autoradiographic localization of [125I]insulin-like growth factor I, [125I]insulin-like growth factor II, and [125I]insulin receptor binding sites in developing and adult rat brain. AB - Insulin-like growth factors I and II (IGF I and IGF II) and insulin itself, which are structurally related polypeptides, play an important role in regulating brain growth and development as well as in the maintenance of its normal functions during adulthood. In order to provide a substrate for the better understanding of the roles of these growth factors, we have investigated the anatomical distribution as well as the variation in the density of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites in developing and adult rat brain by in vitro quantitative autoradiography. The distributional profile of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites showed a widespread but selective regional localization throughout the brain at all stages of development. The neuroanatomic regions which exhibited relatively high density of binding sites with each of these radioligands include the olfactory bulb, cortex, hippocampus, choroid plexus, and cerebellum. However, in any given region, receptor binding sites for IGF I, IGF II, or insulin are concentrated in anatomically distinct areas. In the cerebellum, for example, [125I]IGF II receptor binding sites are concentrated in the granular cell layer, [125I]insulin binding sites are localized primarily in the molecular layer, whereas [125I]IGF I receptor binding sites are noted in relatively high amounts in granular as well as molecular cell layers. The apparent density of sites recognized by each radioligand also undergoes remarkable variation in most brain nuclei, being relatively high either during late embryonic (i.e., IGF I and IGF II) or early postnatal (i.e., insulin) stages and then declining gradually to adult levels around the third week of postnatal development. These results, taken together, suggest that each receptor-ligand system is regulated differently during development and thus may have different roles in the process of cellular growth, differentiation, and maintenance of the nervous system. Furthermore, the localization of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites over a wide variety of physiologically distinct brain regions suggests possible involvement of these growth factors in a variety of functions associated with specific neuronal pathways. PMID- 8349851 TI - Impaired motor axon regeneration in the C57BL/Ola mouse. AB - The delayed Wallerian degeneration which occurs in the C57BL/Ola mouse is associated with impaired motor axon regeneration. Following sciatic nerve crush, recovery of the sciatic functional index was delayed and incomplete when compared with recovery in C57BL/6J mice. After facial nerve crush, recovery of whisker movement in Ola mice was also delayed, and there was a prolonged period of partial recovery, not seen in 6J mice. Regeneration rate of the motor axons was measured by the axonal transport technique in sciatic nerve and was approximately 0.7 mm/d for Ola mice, and 4.0 mm/d for 6J mice. Combining these results from our previous work, we conclude that regeneration of both sensory and motor axons is impaired when Wallerian degeneration does not follow its usual time course after injury. PMID- 8349850 TI - Distribution of GAP-43 mRNA in the adult rat brain. AB - Regional distribution of gene expression of the axonal growth-associated protein, GAP-43, was studied in adult rat brains by in situ hybridization autoradiography to determine the features of mature neuronal populations that synthesize GAP-43 protein. Such synthesis appears to correlate with axonal growth during maturation and regrowth after axotomy. In most adult neurons, the sharp decline in GAP-43 gene expression implies a reduced capacity for axonal growth. Neurons capable of extending axonal knobs in the absence of injury may indicate a "plasticity" underlying dynamic processes of interaction between neurons and their synaptic targets. Antisense and sense (control) riboprobes were used on serial sections in the three principal axes, and the magnitude of hybridization signal was examined to determine regional patterns. GAP-43 mRNA levels are pronounced in diverse neuronal groups including the locus coeruleus, raphe nn., dopaminergic nigral and ventral tegmental nn., mitral cells, hippocampal CA3, inferior olivary n., vagal motor n. and other parasympathetic preganglionic neurons, select thalamic midline and intralaminar nn., several specific nn. of the hypothalamus and basal forebrain, the granular layer of cerebellar cortex, the infragranular neocortex, and the granular olfactory paleocortex; there is a substantial range in the magnitude of expression. Regions revealing minimal signal include most thalamic sensory relay nuclei, the granule neurons of the olfactory bulb and dentate gyrus, and the caudate and putamen. Possible concomitants of GAP-43 expression include regulation of ion flux and neurotransmitter release. Those neurons with long, extensively dispersed and numerous synaptic connections display the strongest signals and may possess the greatest propensity for continuous growth and turnover of their axon terminals, in contrast to short-axon and specific projection neurons exhibiting minimal levels. These data may enable inferring which populations display normal or experimentally induced axonal growth. PMID- 8349852 TI - Localization and differential expression of FMRFamide-like immunoreactivity in the nematode Ascaris suum. AB - By immunocytochemical and immunohistochemical methods, FMRFamide-like immunoreactivity (FLI) was localized to many neurons and processes in the Ascaris nervous system, including the head, tail, and lateral lines. Some of these cells were identified; they included sensory neurons, interneurons, and motor neurons. FLI was also present in the pharyngeal neurons and in their varicosities near the surface of the pharynx. By HPLC analysis of extracts, only a subset of the FMRFamide-like peptides (FLPs) expressed in Ascaris heads, and heads from which the pharynx had been removed, were expressed in the pharynx. Furthermore, FLPs appeared to be differentially expressed in female heads and tails and male heads and tails. Acetone and acid methanol differentially extracted subforms of FLI from Ascaris heads and from C. elegans. PMID- 8349853 TI - Syndromes associated with melanocytic nevi. AB - Melanocytic nevi have been reported in association with several congenital syndromes. This review describes the clinical and cutaneous manifestations of six syndromes associated with congenital melanocytic nevi, two associated with acquired nevi, and six associated with melanocytic nevi in which insufficient evidence exists to classify them as congenital or acquired. It is important to recognize these associations to evaluate and counsel patients with melanocytic nevi. Early recognition will also facilitate timely intervention. PMID- 8349854 TI - Asymmetric periflexural exanthem of childhood. AB - BACKGROUND: We report an expanded series of patients with a distinctive childhood exanthem. OBJECTIVE: Our goal was to describe a new clinical entity. METHODS: This is a clinical study. Twenty-one patients, mostly seen in the spring and late fall, are described. RESULTS: The mean age at onset was 21 months. The eruption began in the periflexural area (close to the axilla, in which an enlarged lymph node was noted in most cases) and spread in an asymmetric pattern, leading to a more generalized eruption in 11 patients. Complete resolution occurred in 3 to 6 weeks. CONCLUSION: An inoculation disease was first suspected, but a systemic viral exanthem seems more probable. We propose to name this eruption asymmetric periflexural exanthem of childhood. PMID- 8349855 TI - Cutaneous T-cell lymphoma associated with HIV infection. AB - BACKGROUND: Mycosis fungoides-type cutaneous T-cell lymphoma is uncommon in association with human immunodeficiency virus type 1 (HIV-1) infection. Reported patients have a high incidence of CD8+ T-cell lymphomas and erythroderma, are usually severely immunocompromised, and rapidly die. Chronic, more typical patch plaque mycosis fungoides-type cutaneous T-cell lymphoma in association with HIV-1 infection has not been reported. OBJECTIVE: We report two cases of stage 1B epidermotropic mycosis fungoides-type cutaneous T-cell lymphoma in HIV-1-infected men with no history of the acquired immunodeficiency syndrome. METHODS: Clinical and laboratory data, including lesional immunophenotypic and immunogenotypic findings of two patients with HIV-1-associated cutaneous T-cell lymphoma, were studied. RESULTS: Immunohistochemical analysis of skin determined the lesional infiltrate of one patient to be CD8+ (Leu-2+), CD7- (Leu-9-), and Leu-8- with germline lesional skin and blood T-cell receptor genes. The other was CD4- (Leu 3+), CD2- (Leu-5-), CD7- (Leu-9-), and Leu-8- with beta-chain T-cell receptor gene rearrangement in lesional skin and blood. Circulating Sezary cells were not detected in either patient. Peripheral CD4/CD8 T lymphocyte numbers did not appear to correlate with cutaneous disease activity or the predominant lesional T cell subtype. Both patients were responsive to standard therapies and have experienced prolonged survival in excess of that generally reported for HIV-1 associated systemic peripheral and cutaneous T-cell lymphomas. CONCLUSION: In the absence of severe immunodeficiency, HIV-1-infected patients with concomitant cutaneous T-cell lymphoma may follow a more typical slowly progressive course. PMID- 8349856 TI - Cutaneous neoplasms in a military population of HIV-1-positive patients. Military Medical Consortium for the Advancement of Retroviral Research. AB - BACKGROUND: In HIV-1-positive patients there have been no prospective studies that show an increase in cutaneous neoplasms. OBJECTIVE: We observed HIV-1 positive patients to determine whether or not there was an increased incidence of cutaneous malignancies. METHODS: A total of 724 HIV-1-positive patients were examined during a 36-month period for the development of cutaneous malignancies. RESULTS: The most common cutaneous neoplasm found was Kaposi's sarcoma, especially in patients with late-stage disease. Basal cell carcinomas were the next most frequent tumor. We have also seen three malignant melanomas and two squamous cell carcinomas. Five patients had malignant lymphoma. One patient had a primary lymphoma of subcutaneous soft tissue; in one patient multiple cutaneous lesions developed. CONCLUSION: The distribution and prevalent types of cutaneous neoplasms in HIV-1-positive patients appear to differ from those found in other immunosuppressed populations. This may be the result of the different patterns and periods of immunosuppression in these patients and/or associated cocarcinogens to which these patients frequently are exposed. PMID- 8349857 TI - Cultured keratinocyte allografts and wound healing in severe recessive dystrophic epidermolysis bullosa. AB - BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) frequently have painful erosions that are slow to heal. There is no definitive treatment; therefore any therapy that improves wound healing would be beneficial to these patients. OBJECTIVE: Our purpose was to assess the effects of cultured allogeneic keratinocytes on wound healing in RDEB. METHODS: Ten patients with RDEB and dermatome-induced superficial dermal wounds were studied. Cultured keratinocyte grafts were applied to part of the wound, with another part left ungrafted. Both sites were assessed clinically and microscopically, particularly with regard to basement membrane zone reconstitution. RESULTS: Apart from minor differences in keratinocyte differentiation and a moderate analgesic effect induced by the graft, there were no other distinguishing findings in wound healing in the grafted and nongrafted sites. CONCLUSION: There was little clinical benefit from cultured keratinocyte allografts in wound healing in RDEB. However, this study showed that RDEB keratinocytes have an inherent capacity to express some type VII collagen epitopes transiently during wound healing, although this was not associated with the detection of anchoring fibrils. PMID- 8349858 TI - Lack of selective attendance of participants at skin cancer/melanoma screening clinics. AB - BACKGROUND: Whether persons who come for skin cancer/melanoma screening are those at highest risk for the disease remains a debatable issue. OBJECTIVE: Our purpose was to evaluate the appropriateness of self-selection of persons attending screening clinics. METHODS: We studied the frequency of malignant and/or premalignant clinical diagnoses according to certain demographic characteristics as a measure of selective attendance among 2463 persons screened in the regions of Arnhem and Eindhoven in 1990. RESULTS: The referral rates for tentative malignant and/or premalignant diagnoses were more or less similar in men (11.8%) and women (9.6%); in persons with symptoms (11.6%) and those who were symptom free (9.3%); in attendants from the towns in which the screenings were held (11.4%) and those coming from distant communities (9.0%); and in persons who attended for specific skin lesions (10.7%) and those who opted for general skin examination (8.8%). The referral rate was 9.2% in persons younger than 70 years of age against 18.5% in those 70 years of age or older (p < 0.001). Most presumptive melanoma diagnoses (15 of 22) were recorded in persons 50 years of age or older. CONCLUSION: Our findings suggest that participants of free skin cancer/melanoma screening clinics, on average, are unable to estimate their own risk profile properly. PMID- 8349859 TI - Psoriasis in Australian twins. AB - BACKGROUND: Occurrence of psoriasis has been found to be strongly genetically controlled in Northern European and U.S. twin and family studies. OBJECTIVE: Our purpose was to assess cumulative incidence and heritability of psoriasis in the Australian population. METHODS: Australian twins reporting psoriasis on a screening questionnaire received from 3808 pairs were mailed a detailed instrument designed to validate the diagnosis, supplemented by telephone interview and examination of medical records. RESULTS: Only 94 of 160 subjects who screened positive were confirmed to have psoriasis. The cumulative incidence of confirmed psoriasis was 2% in 30- to 60-year-old subjects. The monozygotic twin casewise concordance for confirmed psoriasis was 35% (12 of 34 pairs), and the dizygotic twin concordance 12% (5 of 43 pairs), giving an estimated heritability of 80%, was similar to that found in a genetic reanalysis of three previous twin studies. A case-control analysis of psoriasis-discordant twin pairs found no evidence for influences of alcohol or coffee intake, overweight, birth weight, or personality in the origin of psoriasis. CONCLUSION: Occurrence of psoriasis in the Australian population is highly heritable, but identical twins are often discordant; the factor responsible for the onset of disease in one twin and not the other is unclear. PMID- 8349860 TI - Hereditary palmoplantar keratoderma, type papulosa, in Croatia. AB - BACKGROUND: Hereditary palmoplantar keratoderma (HPPK), type papulosa, is rare, and epidemiologic data are sporadic and inconsistent. An epidemiologic population study of this disease has not been performed previously. OBJECTIVE: We performed a large population study on prevalence of HPPK, type papulosa, in Croatia. METHODS: The data were collected from medical records of dermatology departments throughout Croatia; 14 patients and their relatives were examined. Histopathologic studies were performed in 11 of these 14 patients. RESULTS: Fifty five patients were identified and the prevalence was 1.17 per 100,000 inhabitants. All 55 patients belonged to 20 different families. An autosomal dominant mode of inheritance was confirmed in 13 families. All 14 patients examined by the authors had both palmar and plantar lesions; the volar aspects of fingers were also involved. Thickened nails were observed in four patients, and no significant skin lesions were found elsewhere. CONCLUSION: HPPK, type papulosa, is rare, and its prevalence in Croatia is about four times lower than HPPK, Unna-Thost type. It should be considered a distinct entity. PMID- 8349861 TI - Topical treatment of New World cutaneous leishmaniasis in Belize: a clinical study. AB - BACKGROUND: Many studies have been performed during the past decade to find an effective topical therapy for cutaneous leishmaniasis (CL). OBJECTIVE: Our purpose was to evaluate the effect of paromomycin ointment (P-ointment) containing 15% paromomycin sulfate and 12% methylbenzethonium chloride on Belizean patients with New World CL. METHODS: Fifty-three patients were treated twice daily for 14 to 21 days with P-ointment. RESULTS: Sixty-eight percent of the patients healed, 6% had a delayed cure, and 26% did not respond. No toxic effects from the ointment were observed. CONCLUSION: Topical paromomycin is as efficacious in the treatment of New World CL as other currently accepted modalities that are potentially more toxic. PMID- 8349862 TI - Diet and dermatology. The role of dietary manipulation in the prevention and treatment of cutaneous disorders. AB - The role of dietary manipulation and vitamins in the prevention and treatment of certain skin diseases is reviewed. Manipulation of nutrition by either diet restriction or supplementation can effect cutaneous disorders such as skin cancer, wound healing, atopic dermatitis, psoriasis, and dermatitis herpetiformis. PMID- 8349863 TI - Cutaneous mucormycosis resembling superficial granulomatous pyoderma in an immunocompetent host. AB - Primary cutaneous mucormycosis is uncommon and occurs mainly in immunosuppressed or diabetic patients or after localized trauma. We report a case of cutaneous mucormycosis in an immunocompetent man in whom no definite precipitating factors could be identified; initially, superficial granulomatous pyoderma was suspected clinically. The lesion was successfully treated with debridement, local wound care, parenteral administration of amphotericin B, and ultimately by surgical excision and split-thickness skin grafting. PMID- 8349864 TI - Necrobiotic xanthogranuloma without periorbital lesions. AB - Cutaneous necrobiotic xanthogranuloma is rare and closely resembles widespread necrobiosis lipoidica. It is important to recognize this skin disorder because of its strong association with paraproteinemia and, in some cases, with a hematologic malignancy. We describe two patients with necrobiotic xanthogranuloma who are unusual in that they had no periorbital involvement, a feature previously believed to be diagnostic of this condition. PMID- 8349865 TI - Penile squamous cell carcinoma arising from balanitis xerotica obliterans. AB - Squamous cell carcinoma arising from balanitis xerotica obliterans is rarely reported. We describe an 83-year-old man in whom metastatic penile squamous cell carcinoma developed after 18 years of observation for balanitis xerotica obliterans. It is important to recognize the possibility of this uncommon complication of balanitis xerotica obliterans, because survival of patients with squamous cell carcinoma depends on early diagnosis and treatment. PMID- 8349866 TI - Vascular nodules and plaques resembling chronic mucocutaneous candidiasis in a patient with a low interleukin 2 level. AB - A 21-year-old woman had a lifelong history of widespread friable vascular nodules and plaques. Her condition had previously been diagnosed as chronic mucocutaneous candidiasis because of her clinical appearance. Routine studies of immune function were performed in addition to a comparison of cytokine secretion in mononuclear leukocytes of our patient and normal controls. Interleukin 2 secretion by phytohemagglutinin-stimulated mononuclear leukocytes was deficient when compared with six healthy donors (< 300 pg/ml vs 2108 +/- 336 pg/ml). Interleukin 2 deficiency may be a causative factor in cases of unusual vascular proliferation. Treatment with methotrexate, which increases interleukin 2 activity and inhibits neovascularization in vitro, was helpful in our patient. PMID- 8349868 TI - Neonatal pemphigus vulgaris in a child born to a woman in remission. AB - We describe the tenth reported case of neonatal pemphigus that mimicked Bart's syndrome and review previously published cases. Unlike previous cases, the child was born with significant blistering to a mother who was in complete remission throughout the pregnancy. High antepartum maternal titers of anti-intercellular space antibodies, increased maternal disease activity, and maternal disease that requires high doses of corticosteroids or use of combined therapy correlate with poor fetal outcome, including intrauterine death. PMID- 8349867 TI - Severe megaloblastic anemia in a patient receiving low-dose methotrexate for psoriasis. AB - Severe megaloblastic anemia with a normal white blood cell and platelet count developed in a patient with psoriasis vulgaris who was receiving long-term, low dose methotrexate. We believe she had methotrexate-induced folate deficiency anemia with isolated inhibition of the erythrocytic bone marrow line. We review hematologic toxicity from low-dose methotrexate. Physicians caring for patients who receive low-dose methotrexate should be aware that an increase in the erythrocyte mean corpuscular volume may be a useful indicator of folate deficiency and impending toxicity. In addition, folate supplementation may prevent this toxicity (even in patients who do not appear clinically to be folate deficient), although whether methotrexate efficacy diminishes is controversial. PMID- 8349869 TI - Linear Kaposi's sarcoma in HIV disease. PMID- 8349870 TI - Pigmented fungiform papillae of the tongue. PMID- 8349871 TI - Acute reversible central nervous system toxicity associated with low-dose oral cyclosporine therapy. PMID- 8349872 TI - Erythema gyratum repens: direct immunofluorescence microscopic findings. PMID- 8349874 TI - Fixed drug eruption caused by diphenhydramine. PMID- 8349873 TI - Paronychia: a sign heralding an exacerbation of pemphigus vulgaris. PMID- 8349875 TI - Mupirocin treatment of exudative venous ulcers. PMID- 8349876 TI - Hypothalamus-pituitary-adrenal axis suppression by superpotent topical steroids. PMID- 8349877 TI - Beta-adrenergic blocking drugs and psoriasis: the role of an immunologic mechanism. PMID- 8349878 TI - Ectrodactyly-ectodermal dysplasia-clefting syndrome with scalp dermatitis. PMID- 8349879 TI - The spectrum of dermal elastolysis. PMID- 8349880 TI - Sterility of refrigerated injectable collagen syringes. PMID- 8349881 TI - Sterility of refrigerated injectable collagen syringes. PMID- 8349882 TI - Metastatic signet-ring cell melanoma. PMID- 8349883 TI - Mechanisms of hyperosmotic acclimation in Xenopus laevis (salt, urea or mannitol). AB - The acclimation of the clawed toad Xenopus laevis to hyperosmotic solutions of NaCl (balanced solution of sea salt), urea or mannitol was studied. The animals could not be acclimated to salt solutions more concentrated than 400 mosm.1-1. Urea was tolerated till 500 mmol.1-1. Plasma osmolality was always hyperosmotic to the environmental solution, but with diminished osmotic gradient at the highest tolerated solutions. Plasma urea concentration approached 90 mmol.1-1, similar in the three solutions of acclimation. Urine volume was very small under all conditions. Serum aldosterone and corticosterone did not differ significantly, although there was a slight tendency towards lower aldosterone in the NaCl solution. In vivo water uptake in tap water acclimated animals was very small, and was higher in the other groups. Only the salt- and urea-acclimated, but not the tap water and mannitol-acclimated groups responded with a clear increase following injection of oxytocin or theophylline. In vitro urea fluxes were similar and invariable in both directions under all conditions. No significant effect of theophylline was observed. Sodium transport measured by the short-circuit technique in vitro was lower in salt- and mannitol-acclimation conditions, and was stimulated significantly under all conditions in response to serosal oxytocin or theophylline. It is concluded that Xenopus laevis can osmoregulate at a limited range of external solutions. It is limited in the increase of its plasma urea concentration; the transport properties of the skin do not change very much upon acclimation, except for the hydroosmotic response to oxytocin. PMID- 8349885 TI - Diurnal variation in thermal and metabolic parameters of the golden hamster (Mesocricetus auratus). AB - The purpose of this study is to examine diurnal variation in several thermal and metabolic parameters of the golden hamster, Mesocricetus auratus. Metabolic rate, core temperature, and evaporative water loss were measured during night and day at several ambient temperatures. Wet minimal thermal conductance, dry minimal thermal conductance, basal metabolic rate, minimal net heat production and the lower critical temperature difference were estimated from these measurements. Wet and dry minimal thermal conductance, evaporative water loss, core temperature, basal metabolic rate, and lower critical temperature difference were greater during the active phase than during the resting phase. The diurnal variation in wet minimal thermal conductance was much smaller than that predicted from published allometric equations. The diurnal variation in wet minimal thermal conductance was 9% of the 24-h mean. The diurnal variation in dry minimal thermal conductance was 26% of the 24-h mean. The higher active-phase core temperature and basal metabolic rate may function to enhance peak metabolic performance during the active phase. The lower resting phase metabolism and core temperature may reduce energetic costs. The greater active-phase lower critical temperature difference may be a result of the greater active-phase basal metabolic rate. Diurnal variation in minimal thermal conductance may be caused by changes in peripheral circulation. PMID- 8349884 TI - Contractile responses in rat extensor digitorum longus muscles at different times of postnatal development. AB - Some contractile properties of small bundles (100-200 microns diameter) of muscle fibres isolated from the extensor digitorum longus muscle of rats at different times of development were compared. An increase of resting potential was observed in these muscles from -26.9 mV at 1 day of age to -72.6 mV at 3 months. Twitch tension and duration of postnatal muscles 1-7 days were diminished by reducing [Ca]o (substituted by Mg2+) or adding inorganic cations (Ni2+, Cd2+, La3+), unlike in the oldest animals (14 days-3 months postnatal) where twitch responses were unaffected. In the latter, potentiation of the twitch tension was even recorded in the presence of Ni2+ (0.5-1 mmol.1-1) and Cd2+ (0.5-2 mmol.1-1). Properties of activation and inactivation of the developed tension following elevation of [K]o to 15-200 mmol.1-1 were analysed at the same stages of postnatal development. In contrast to the tension-membrane potential curves for activation, which presented an average negative shift of -17.6 mV between 1 day postnatal and 3 months of age, a voltage dependence of inactivation similar to that encountered in adult extensor digitorum longus muscles, was already reached at 7 days of age. These results suggest an asynchronism in the maturation of the potential-dependent characteristics of the depolarization-contraction coupling mechanism. Furthermore, during the first week postnatal, in relation with poorly developed membrane systems and low [Ca]i-recycling capability, [Ca]o plays a fundamental role in maintaining contraction by replenishing the intracellular calcium pool. PMID- 8349886 TI - Effects of water restriction on digestive function in two macropodid marsupials from divergent habitats and the feral goat. AB - The effects of water restriction on digestive function in the euro (Macropus robustus erubescens) found in the arid zone of inland Australia, the eastern wallaroo (M.r.robustus) from more mesic regions of eastern Australia, and the feral goat (Capra hircus) found throughout the range of M. robustus, were compared in order to examine some physiological adaptations required by herbivores for the exploitation of arid environments. Eight animals of each species were held in individual metabolism cages in temperature-moderated rooms and given a chopped hay diet ad libitum. Half the animals were restricted to 40 ml water.kg-0.80.day-1. This was 40%, 32% and 57% of voluntary drinking water intake in the euro, wallaroo and goat, respectively. All species responded to water restriction by reducing faecal, urinary and evaporative water losses in association with reductions in feed intake. All animals increased urine osmolality and electrolyte concentrations but not to maximal levels, while packed cell volume and plasma osmolality and electrolyte concentrations were unaffected by water restriction. The euro displayed a suite of characteristics that separated it from the wallaroo in terms of physiological adaptation, including lower voluntary water intake, an increase in fibre digestibility and maintenance of nitrogen balance during water restriction, and lower faecal water efflux associated with a consistently lower faecal water content (54% versus 59% water in the wallaroo during water restriction, P < 0.05). The euro's colon was 37% longer (P < 0.01) than that of the wallaroo. The goat had the lowest faecal water efflux (P < 0.05) and the longest colon (P < 0.001). Water restriction did not affect water content in digesta, nor short-chain fatty acid concentrations or production rates in vitro. Total body water, as a proportion of body mass, was depressed (P < 0.05) in the macropodids, but not in the goat. The reduction in dietary nitrogen intake, which accompanied water restriction, was partially compensated by an increase in urea degradation in the gut from 68% to 76% of urea synthesis water-restricted macropodids. These responses to water restriction are discussed in relation to those reported in other macropodid and ruminant species. PMID- 8349887 TI - Allied dental education: past, present, and future. PMID- 8349888 TI - Overview of allied health issues in contemporary health care. PMID- 8349889 TI - The future of allied dental education: creating a professional team. PMID- 8349890 TI - The future of allied health in higher education: where does it belong? PMID- 8349891 TI - Validation of a motor skills performance theory with applications for dental education. AB - While several investigations assessing applications of contemporary motor learning theory to preclinic laboratory instruction have been successful, they provide only indirect and incomplete validation of theoretical constructs. This study's purpose was to further evaluate the validity of salient constructs through the use of a validation technique called verbal self-reporting, and to describe applications for dental education. Subjects were videotaped completing a preparation. Later, the tape was replayed and a structured interview used to stimulate recall of mental processes that occurred during the preparation. Transcribed self-reports were classified by two calibrated raters into categories corresponding to the constructs of interest. Results confirm many of the constructs' characteristics. Subjects reported that they a) defined the desired outcome in detail before beginning production; b) defined performance strategies that would be useful for different aspects of the preparation; c) constantly generated knowledge of results during the course of production in order to directly assess the adequacy of the product; and d) generated knowledge of performance as an indirect assessment of product acceptability especially when visual access was impeded. These results support previous applications of the theory to dentistry and have important implications for the improvement of instruction in preclinic laboratory courses. PMID- 8349892 TI - The evolution of dental education--a European perspective. PMID- 8349893 TI - APEX: an experiential education program. PMID- 8349894 TI - A time for change of tooth numbering systems. AB - Tooth numbering provides dentists with an essential shortcut in clinical record keeping. Today, three systems are favored worldwide: the Zsigmondy/Palmer system, the universal system, and the FDI two-digit system. Histories of these tooth numbering methods are traced, and the strengths and deficiencies of each are discussed. The FDI two-digit system-used throughout the world, but not in the USA is the only method that makes visual sense, cognitive sense, and computer sense. It deserves consideration by American dentists as our official tooth numbering system. PMID- 8349895 TI - Curriculum guidelines for behavioral science. Section on Behavioral Sciences of the American Association of Dental Schools. PMID- 8349896 TI - Hair today, gone tomorrow. PMID- 8349898 TI - Navigating through tissue expansion terminology. PMID- 8349897 TI - Intracutaneous butterfly suture with absorbable synthetic suture material. Technique, tissue reactions, and results. AB - BACKGROUND: Tension on surgical wound edges is often an obstacle to proper closure and good cosmetic results in dermatologic surgery. OBJECTIVE: A buried, butterfly-shaped, interrupted suture has been developed to remedy this. The suture is anchored very broadly in the corium, the knot is below the corium. The butterfly suture can be supplemented by a temporary running suture or by close set, superficially placed interrupted sutures. METHODS: This technique was studied in a follow-up of 876 operations, with histologic study of 60 scars resulting from the suture. In particular, the specific advantages and disadvantages of two synthetic suture materials were compared: monofilament (polydioxanon) and polyfilament (polyglactin 910). RESULTS: Polydioxanon sutures were found to be clinically superior. It was important, however, that the suture knot be deeply anchored and that the surgeon be experienced. CONCLUSION: Cosmetic results of 18,000 procedures with this suture over a period of 6 years were found to be clearly better than those of surgery with conventional sutures. PMID- 8349899 TI - Scalp extension. AB - BACKGROUND: Surgery to correct extensive alopecia requires increasing the surface of hair-bearing scalp and removing bald scalp. Two commonly used methods, scalp expansion and scalp reduction, have disadvantages. OBJECTIVE: To describe a new method, scalp extension, that employs a thin sheet of bioplastic (an extender) stretched and attached with hooks to the galea after scalp reduction. METHODS: The surgical technique is described and the results compared with those of patients who have undergone scalp reduction and scalp expansion. A study of the first fifteen cases treated is presented. RESULTS: During the few weeks that the extender is implanted, the constant tension it exerts on the galea causes a progressive stretching of the scalp. Data from the first fifteen cases treated reveal eradication of more extensive bald areas than with scalp reduction, making it possible to cut the number of operations necessary in half while considerably shortening total treatment time. The absence of major side effects, along with the absence of any deformation of the scalp (unlike scalp expansion), explains the excellent acceptability of the instrument by patients. CONCLUSION: Scalp extension appears to be a useful adjunctive technique in hair replacement and reconstructive surgery, and has distinct advantages over standard scalp reduction and tissue expansion techniques. PMID- 8349900 TI - Transcranial eosinophilic granuloma manifested by a subcutaneous scalp mass. Differential diagnosis in children. AB - BACKGROUND: The differential diagnosis of nodular scalp lesions in a child is surprisingly extensive. OBJECTIVE: To present a case of eosinophilic granuloma that was manifested by a scalp mass in a pediatric patient. METHODS: The case is presented and the relevant literature is reviewed. CONCLUSIONS: The seriousness of some of these lesions requires a thorough evaluation, including noninvasive imaging, and carefully planned surgical intervention so that effective diagnosis and treatment are ensured. Surgical exposure of unsuspected central nervous system connections may lead to infection, hemorrhage, seizures, or other significant morbidity and mortality. PMID- 8349901 TI - Duplex scanning and light reflection rheography in the assessment of the severity of short saphenous vein incompetence. AB - BACKGROUND: Duplex ultrasound assessment of veins in the popliteal fossa is an accepted alternative to venography. Light reflection rheography provides additional quantitative information on venous reflux in chronic venous insufficiency. OBJECTIVE: To use duplex ultrasound and light reflection rheography to study the venous reflux patterns in the popliteal fossa in a group of patients. METHODS: Duplex ultrasound examination and light reflection rheography were used in the assessment of the severity of short saphenous vein incompetence. RESULTS: The study revealed that any associated deep venous reflux which was detectable beyond the saphenopopliteal junction represented a more advanced stage of superficial venous insufficiency. CONCLUSIONS: Light reflection rheography, as a semiquantitative test, provided useful additional information to duplex scan findings in assessing venous reflux of the popliteal fossa. Short saphenous vein reflux with functional deep venous incompetence was associated with shorter venous refilling times and clinically represented a more advanced stage of primary varicose vein disease. PMID- 8349902 TI - The prevention of cutaneous necrosis following extravasation of hypertonic saline and sodium tetradecyl sulfate. AB - BACKGROUND: Most authors have recommended treating extravasation during sclerotherapy by infiltrating the area with 0.9% sodium chloride and/or procaine. OBJECTIVE: To evaluate interventions in the prevention of necrosis following intradermal injection of 23.4% sodium chloride and 3% sodium tetradecyl sulfate. METHODS: Following intradermal 23.4% sodium chloride (Study I) or 3% sodium tetradecyl sulfate (Study II), subjects (Sprague-Dawley rats) received either no treatment or injections of 0.9% sodium chloride, sterile water, 1% procaine, or hyaluronidase. Groups were compared regarding incidence and size of necrosis. RESULTS: In study I, hyaluronidase treated groups had significantly fewer and smaller areas of necrosis than other groups. In study II, the hyaluronidase group developed significantly fewer ulcers than the 0.9% sodium chloride group. The 0.9% sodium chloride group had significantly larger ulcers than other groups. CONCLUSION: In the model studied, hyaluronidase was the only effective treatment in the prevention of necrosis. Following 3% sodium tetradecyl sulfate, 0.9% sodium chloride was associated with larger ulcers than other groups. PMID- 8349903 TI - Postsclerotherapy hyperpigmentations. Chromated glycerin as a screen for patients at risk (a retrospective study). AB - BACKGROUND: Chromated glycerin reportedly causes less post-sclerotherapy hyperpigmentations than polidocanol. OBJECTIVE: To investigate whether replacing polidocanol with chromated glycerin lowers the incidence of postsclerotherapy hyperpigmentation. METHODS: Retrospective study of 134 records of patients treated for leg telangiectasia. At the first session only chromated glycerin was injected. From the second session on treatment was continued--according to the response--either with chromated glycerin or with the stronger polidocanol. RESULTS: Chromated glycerin caused strong sclero-inflammatory reaction in 27% of patients, who were therefore treated with chromated glycerin only; in the remaining 73%, chromated glycerin was replaced with polidocanol, because of mild (or absent) reaction. Postsclerotherapy hyperpigmentation developed in three patients, all treated with chromated glycerin, while no postsclerotherapy hyperpigmentation developed in the patients treated with polidocanol. CONCLUSIONS: Single "trial" session with chromated glycerin permits to select patients at risk of developing postsclerotherapy hyperpigmentation, and treat these with a milder sclerosant. This approach also reduced the incidence of early postsclerotherapy hyperpigmentation compared with similar series treated with polidocanol alone. PMID- 8349904 TI - The effect of pre-education on patient compliance with full-body examination in a public skin cancer screening. AB - BACKGROUND: Public skin cancer screening has become increasingly common in recent years. However, currently there is no standardized procedure for these screenings. Full body skin examination as opposed to examination of sun-exposed areas offers several advantages, including the opportunity to diagnose early melanoma in areas normally covered by clothing. Disadvantages of full body skin examination include patient resistance because of inconvenience and concerns about privacy and modesty. The additional time involved in full body skin examination may also be an impediment. OBJECTIVE: In a randomized double-armed study, we studied whether patients were more likely to develop a positive attitude towards full body skin examination if they were advised beforehand, in writing, of the logic underlying the need for a complete examination. METHODS: Patients presenting to a public skin cancer screening were divided into two groups. Group A (N = 111) received a written explanation of the need for full body skin examination and Group B (N = 175) received no information. Patients were then surveyed, after the screening, about their attitudes towards full body skin examination. RESULTS: Those who received pre-education were less likely (P < .05) to be concerned about a genital examination. Those who were concerned about a genital exam were compared with those who were not concerned about a genital exam, the former patients were: 1) younger (P < .05); 2) more concerned about privacy (P < .001); and 3) preferred a physician of the same sex (P < .001). CONCLUSION: Providing patients with information about the need for full body skin examination decreases concern about undergoing a skin genital exam and may minimize resistance to full body skin examination in public skin cancer screenings. PMID- 8349905 TI - A visit to the office of Dr. Emanuel Marritt. PMID- 8349906 TI - Re: Acu-Guard. PMID- 8349907 TI - Re: Punch biopsy. PMID- 8349908 TI - Wound healing. An overview. PMID- 8349909 TI - Basics of cutaneous wound repair. AB - BACKGROUND: Cutaneous wound repair consists of multiple integrated networks of cell-matrix-cytokine interactions. It is generally believed that a better understanding of these networks will lead to improved care of cutaneous wounds, whether freshly made by the surgeon's scalpel or previously existing and not healing secondary to underlying abnormalities. OBJECTIVE: This review is intended to update the readership in some of the salient aspects of wound repair networks. METHODS: To facilitate the review of multiple integrated networks, cutaneous wound repair was arbitrarily divided into three phases: inflammation, tissue regeneration including re-epithelialization and granulation tissue formation, and tissue reorganization. RESULTS: Throughout the entire process of wound repair it is clear that cells produce or alter various cytokines and extracellular matrix. The cytokines and matrix in turn alter the behavior of the producer cells (autocrine response) or neighbor cells (paracrine response). CONCLUSION: The dynamic reciprocity among cells, cytokines, and matrix material helps explain how integrated wound healing networks are sequential as well as tightly controlled. PMID- 8349910 TI - Growth factors and wound healing. AB - BACKGROUND: Over the last decade, there has been an exponential increase in our knowledge of the biology of growth factors. The hope has been and remains that these potent biologic agents will effect a fundamental improvement in the way we treat wounds. OBJECTIVE: We will discuss the biology of growth factors and the dramatic effects these proteins have on cell proliferation, cell chemotaxis, and on the formation of extracellular matrix molecules. RESULTS: Growth factors are extremely potent biologic agents that show promise in accelerating wound repair in both animal and human studies. They improve granulation tissue, enhance tensile strength, and promote reepithelialization. Cosmetic effects are also to be expected by antagonizing and blocking the action of these peptides. CONCLUSION: Growth factors are likely to become an important therapeutic tool for the dermatologic surgeon. PMID- 8349911 TI - Occlusive dressings. AB - BACKGROUND: Although occlusive dressings speed epithelialization, reduce inflammation and tenderness, reduce the chance of infection, stimulate healing of chronic wounds, and produce less scarring, they are still underutilized by physicians and nurses. The principal reasons for their underutilization are fear of infection, the time needed for instructing patients in their use, a lack of knowledge about occlusive dressings, and the general unavailability and high cost of the dressings. METHODS: This chapter describes the principles which help in selection of the proper dressing, discusses the mechanisms of action of occlusive dressings, lists some novel new occlusive dressings, and emphasizes some of the drawbacks of occlusive dressings for chronic wounds. CONCLUSION: While occlusive dressings have become an important treatment protocol, their role in opening the minds of clinicians to the possibility of controlling the repair process may be their greatest contribution to medical science. PMID- 8349912 TI - Wound care after office procedures. AB - A knowledge of wound healing physiology and how it is influenced by wound dressings is valuable information for all dermatologists. Such knowledge enables the dermatologist to give authoritative advice on postoperative wound care and more importantly, to use wound dressings as a complement to good planning and surgical technique in order to optimize the conditions for rapid healing following office surgical procedures. PMID- 8349913 TI - A review of topical agents for wounds and methods of wounding. Guidelines for wound management. AB - This article reviews the effects of antiseptics, antimicrobials, hemostatic agents and surgical methods on the incidence of wound infection and the process of wound healing. A set of guidelines is provided to help decide what to apply topically to wounds and which method of wounding to select in order to achieve the best possible outcome in wound healing. PMID- 8349914 TI - Keloids and hypertrophic scars. AB - BACKGROUND: Keloids and hypertrophic scars are benign fibrous growths which usually occur after trauma in predisposed individuals. Their etiology, clinical manifestations and treatment are diverse. OBJECTIVE: The purpose of this article is to review the pertinent literature concerning keloids and hypertrophic scars as well as present my own perspective on the subject. It is my hope that the information contained herein will help both the dermatologist and dermatologic surgeon better understand and manage these vexing lesions. METHODS: Medline literature search as well as original material. RESULTS: There is no one right way to treat all keloids and hypertrophic scars. Treatment results have been variable. CONCLUSION: The management of keloids and hypertrophic scars can be difficult and frustrating for both patient and physician. A better understanding of keloid pathogenesis may lead to improved therapies by which keloid growth and regrowth may be obviated. PMID- 8349915 TI - Lasers for the stimulation or inhibition of wound healing. PMID- 8349916 TI - Electrical stimulation to heal dermal wounds. AB - BACKGROUND: Numerous human and animal efficacy studies have demonstrated that electrical stimulation of the correct charge, density and total energy causes dramatically improved healing of dermal wounds. The investigations of biological actions (in vitro, animal, and human) demonstrate several effects that go a long way to explaining why electrical stimulation works. OBJECTIVE: To discuss recent research and advances in electrical stimulation of wound healing. RESULTS: Based on the latest scientific understanding of the wound healing process, one would expect a beneficial outcome from a therapy what decreases edema, debrides necrotic tissue, attracts neutrophils and macrophages, stimulates receptor sites for growth factors, stimulates growth of fibroblasts and granulation tissue, increases blood flow, stimulates neurite growth, induces epidermal cell migration, prevents post-ischemic oxygen radical-mediated damage, inhibits bacteria, and reduces numbers of mast cells. CONCLUSION: Taken together, the efficacy studies and the "mechanism of action" studies provide compelling, scientific evidence that electrical stimulation is safe and effective for promoting the healing of dermal wounds. PMID- 8349917 TI - Essentials of pressure ulcer treatment. The diabetic experience. AB - BACKGROUND: Diabetes accounts for over half of the lower extremity amputations in the United States. However, ulcers of the diabetic foot can often be treated successfully and amputations avoided. OBJECTIVE: To review treatment of diabetic foot ulcers. RESULTS: Physicians must recognize the critical clinical and diagnostic features of ischemic and neuropathic ulcers. Therapy is directed towards vascular repair in the ischemic ulcer and relief of weight bearing through casting and shoes with molded insoles in the neuropathic ulcer. Sound principles of wound care apply to all ulcers. CONCLUSION: For successful preventive foot care patients and physicians need to understand how and why ulcers form and the rationale for the types of footwear and care necessary to prevent ulcers. PMID- 8349918 TI - Venous ulceration. AB - BACKGROUND: In the last few years, interest in the pathogenesis and treatment of venous ulceration has been rekindled by novel observations in fibrinolysis and an explosive growth in wound care products, respectively. OBJECTIVE: The purpose of this work is to summarize the salient clinical features of venous ulceration, its proposed pathogenesis, and conventional as well as future treatment modalities. RESULT: Venous ulceration is an increasingly common condition. Its pathogenesis is related to failure of the calf muscle pump, and treatment is directed at effective leg compression, avoidance of contact dermatitis, and proper wound care. CONCLUSION: There is increased interest in both the pathogenic steps involved in venous ulceration and in treatment modalities. We suspect that incremental progress will occur in these areas in the next few years. PMID- 8349919 TI - Inflammatory ulcers. AB - A large number of diseases can eventuate in cutaneous ulceration. This article will review inflammatory disorders which by their nature can directly produce cutaneous breakdown and ulcer formation. Major emphasis is given to those disorders where recent knowledge has improved our understanding of the condition or where new therapeutic agents or maneuvers have become available. This later group consists of vasculitis, disorders caused by small vessel thrombi or embolus and pyoderma gangrenosum. PMID- 8349920 TI - Topical hyperbaric therapy for problem skin wounds. AB - BACKGROUND: Hyperbaric oxygen remains the sole treatment capable of inducing growth of new blood vessels. However, systemic hyperbaric oxygen therapy risks central nervous system and pulmonary toxicity. OBJECTIVE: To describe topical hyperbaric oxygen therapy for the treatment of recalcitrant open wounds. METHODS: Topical and systemic hyperbaric oxygen treatments are described and contrasted from one another. Applications of topical hyperbaric oxygen therapy are described. CONCLUSION: Topical hyperbaric oxygen therapy is useful only for open wounds. The advantages of topical hyperbaric oxygen therapy include low cost, the lack of systemic oxygen toxicity, and effectiveness, allowing this treatment to be prescribed for many patients early in the course of their disease rather than as a last resort. PMID- 8349921 TI - Biologic skin substitutes. AB - BACKGROUND: The ideal skin substitute should closely approximate the skin in function. The substitute should be readily available, easily sterilized and stored, and relatively inexpensive. OBJECTIVE: To describe recent developments in the area of biologic skin substitutes. RESULTS: Considerable advances have been made in keratinocyte and fibroblast culturing when used in conjunction with a biodegradable material as a substrate. CONCLUSION: There is no skin substitute that perfectly mimics autologous skin. However, recent developments show promise. PMID- 8349922 TI - Perforating dermatoses: a review and report of four cases. AB - Perforating dermatoses, an often overlooked entity comprised of Kyrle's disease, perforating folliculitis, reactive perforating collagenosis, elastosis perforans serpiginosa, and acquired perforating dermatosis, are succinctly described, focusing attention on their clinical features, histopathology, treatment, and pathogenesis. The literature on these facets has been extensively reviewed. In addition, three fresh cases of Kyrle's and one of perforating folliculitis have been incorporated to illustrate these conditions. PMID- 8349924 TI - Double cross lip flaps for reconstruction of the lower lip. AB - Squamous cell carcinoma of the lower lip is a common tumor. Of the many methods available for reconstructing lower lip defects after radical excision, we found double cross lip flaps from each lateral side of the upper lip philtrum rotated into the defect of the lower lip to be an effective method, not only functionally but also cosmetically. The main reason why satisfactory results were obtained by this procedure is that the anatomical structure (skin-orbicularis oris muscle mucosa, vermilion) of the upper lip is very similar to that of the lower lip. Our experience is with double cross lip operations in the management of lower lip cancers are described. PMID- 8349923 TI - Significance of elevated serum squamous cell carcinoma (SCC)-related antigen and lactate dehydrogenase (LDH) levels in senile erythroderma following eczema. AB - Clinical and laboratory tests were used to evaluate fourteen patients with senile erythroderma following eczema, and the results were compared with those from four patients with psoriatic erythroderma, two with Sezary syndrome, and twelve with prurigo chronica multiformis or nummular dermatitis. Characteristic laboratory findings included elevated serum squamous cell carcinoma-related antigens (SCC RAg), high lactate dehydrogenase (LDH), peripheral-blood eosinophilia, and a decreased peripheral blood lymphocyte percentage. Following treatment, titers of SCC-RAg and LDH resumed normal levels with remission. In patients with senile erythroderma following eczema, serum IgE was quite high and varied but, in a few instances, was within the normal range. SCC-RAg and LDH may thus be considered useful as markers for evaluating disease conditions of the skin of patients with senile erythroderma following eczema. PMID- 8349926 TI - A case of CD8+ T cell lymphoma occurring during treatment for in situ malignant melanoma of the palate. AB - A 53-year-old Japanese male noticed pigmented lesions on his right upper gingiva and hard palate in February of 1986. Histological examination revealed in situ malignant melanoma. Chemotherapy, beta-interferon, and oral BCG were given. However, tumors subsequently developed in the nasal cavity in March of 1989. The patient died in April of 1990 after developing Garcin's syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Autopsy revealed aggressively infiltrating, whitish tumor masses invading the hard palate, the nasal cavity, the paranasal sinuses, the base of the skull, cranial nerves I-X, and the pituitary body, as well as severe necrosis of the soft palate. However, there was no evidence of malignant melanoma. Instead, these oval tumor cells had atypical nuclei and scanty cytoplasm. They contained no melanin granules, were negative for S-100 protein, and were also negative for various melanoma associated antigens. They were positive for CD2, CD3, and CD8 by avidin-biotin peroxidase complex immunohistochemistry. It was concluded that the patient had CD8+ non-Hodgkin's malignant lymphoma (diffuse, large cell type) of the nasopharyngeal region, which was preceded by in situ malignant melanoma of the palate. PMID- 8349925 TI - Trichilemmal carcinoma occurring in a lesion of solar keratosis. AB - A case of trichilemmal carcinoma occurring in a lesion of solar keratosis was reported. A 92-year-old woman had an erythematous plaque on her face that contained a reddish nodule. Histological examination of the nodule revealed typical features of trichilemmal carcinoma accompanied by those of solar keratosis in the marginal zone. The histological features of the erythematous plaque corresponded with those of solar keratosis. However, in situ the carcinoma developed in the epithelium of a hair follicle as well as in the interfollicular epidermis in the lesion of solar keratosis. We considered it likely that bowenoid malignant transformation occurred in both interadnexal and adnexal epithelium because of actinic damage, and a trichilemmal carcinoma arose. The paper also discussed the histogenesis of trichilemmal carcinoma. PMID- 8349927 TI - Warty dyskeratoma with multiple lesions. AB - A 63-year-old man with multiple nodules and pathological findings of acantholysis is reported as a case of warty dyskeratoma presenting with multiple lesions. The number of nodules is the highest in the records as far as we know. We conclude that warty dyskeratoma originates from the hair follicle. PMID- 8349928 TI - Necrotizing fasciitis appearing with petechiae as the first clinical sign. AB - A 64-year-old Japanese man with necrotizing fasciitis is reported. He developed an Enterobacter agglomerans infection in his left leg without any known causative surgery or trauma, although he had acute myelocytic leukemia as a predisposing condition. Uncommonly, the first clinical sign was petechiae. Surgical debridement could not be performed because of pancytopenia due to his original disease and chemotherapy. The patient died, and an autopsy was performed. Severe intravascular coagulation was observed in the cutaneous infected tissues, while little or no disseminated intravascular coagulation was observed in the major internal organs. The local microorganism factors such as necrotoxins were suspected to cause the intravascular coagulation in the infected tissues. PMID- 8349930 TI - References to contemporary papers on acoustics. PMID- 8349929 TI - Congenital giant pigmented nevus associated with angiolipoma. AB - We report a 20-year-old-Korean woman with a congenital giant pigmented nevus and angiolipoma. She was admitted our department with a large, dark, pigmented lesion on the right flank and abdomen and a slowly growing mass on the right flank area since birth. On biopsy, the specimen taken from the giant pigmented patch showed typical findings of compound nevus. The right flank mass was surgically removed. The specimen was composed of mature fat cells with an increased vascular component. These findings are compatible with angiolipoma. PMID- 8349931 TI - Emerging concepts in mold allergy: what is the role of immunotherapy? PMID- 8349932 TI - Inhaled corticosteroids and severe viral infections. Executive Committee. American Academy of Allergy and Immunology. PMID- 8349933 TI - A double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized cat extract. AB - BACKGROUND: In light of the controversial status of sublingual immunotherapy in patients with allergic rhinitis, we undertook a double-blind study of this form of treatment. METHODS: Forty-one subjects with cat allergy presenting as rhinoconjunctivitis underwent 105 days of sublingual immunotherapy, with 20 subjects receiving a standardized cat extract (total dose approximately 4,500,000 allergy units) and 21 a matching placebo. Effectiveness of treatment was assessed by changes in symptoms and nasal-blockage index during 90 minutes of exposure in an apartment containing cat dander, which was performed before and after the course of treatment. Changes in cat-specific IgG and IgE levels and skin-test reactions were also monitored. RESULTS: Although there were fewer symptoms and less nasal obstruction on cat dander exposure at the end of the study the changes were not significantly different in those receiving active or placebo treatment. Specific IgG and IgE levels and prick skin test results did not change significantly during the course of the study. CONCLUSIONS: We conclude that sublingual immunotherapy with high-dose standardized cat extract was no more effective than placebo in reducing symptoms or affecting immunologic measures of cat sensitivity. PMID- 8349934 TI - Assessment of risk factors for IgE-mediated sensitization to tetrachlorophthalic anhydride. AB - Two groups of workers with occupational asthma caused by tetrachlorophthalic anhydride (TCPA) have been reported on; in only one report was specific anti-TCPA antibody demonstrated. We received a request to investigate respiratory problems among workers at a plant where solenoid coils are manufactured with the use of epoxy resin and where a new TCPA hardener had been introduced in 1988. In response, we conducted a cross-sectional evaluation of 52 current workers and assayed serum samples from 49 workers for TCPA-human serum albumin-specific IgE and IgG by ELISA. Mean airborne TCPA concentrations ranged from 0.21 to 0.39 mg/m3 in 1989 and May 1990 but were considerably lower (less than 0.009 to 0.13 mg/m3) by July 1990 when ventilation was introduced. Workers were classified in four departments as molders (most directly working with TCPA), those intermittently exposed to TCPA, coil assemblers, and office workers. There was a high prevalence of reported work-related respiratory symptoms (from 27% to 39%). The mean decline in FEV1 over the shift in the molders (down 4.1%) was significantly different from the change in the office group (increased 2.5%). Intrashift change in FEV1 was inversely correlated with log personal TCPA concentration (r = -0.47). Of 49 current workers, 15 (31%) had elevated serum TCPA-human serum albumin-specific IgE antibody levels and 19 (39%) had elevated specific IgG levels. The prevalence of specific IgE was highest in the mold and intermittent groups (54%), in comparison with the coil assembly (25%) and office (0%) groups. Those workers who were IgE positive were significantly less likely to be current smokers and had worked significantly longer since 1988. Of those hired in 1988 or after, the proportion of workers who were IgE positive increased with duration of employment category (p value for trend 0.022). Since ventilation was installed and TCPA exposures reduced to less than 0.1 mg/m3, there has been a marked decrease in symptoms and no new cases of occupational asthma among newly hired workers at the plant. PMID- 8349935 TI - Release of chemical mediators and inflammatory cell influx during early allergic reaction in the nose: effect of furosemide. AB - BACKGROUND: We evaluated the effect of furosemide on allergen-induced rhinitis in a double-blind, crossover, placebo-controlled experiment. METHODS: Fourteen patients with rhinitis who were allergic to house dust were nebulized with an intranasal dose of 20 mg of furosemide or placebo before allergen challenge with an extract of Dermatophagoides pteronyssinus (100 BU). Clinical evaluation and nasal lavages with normal saline solution were performed at baseline; after placebo-furosemide nebulization, and at 10, 30, and 60 minutes after allergen challenge. Number of sneezes and a composite symptom score were recorded to evaluate clinical response. Prostaglandin E2 (PGE2), PGD2 peptide leukotrienes and 15-hydroxy, 5,8,11,13-eicosatetraenoic acid (15-HETE) were measured by radioimmunoassay in nasal lavages. Cells were counted and classified as epithelial cells, neutrophils, eosinophils, and others. RESULTS: No differences in either clinical symptoms or cell influx after allergen challenge were found between furosemide and placebo groups. PGE2 levels did not change after provocation, and furosemide had no effect on its production. Ten minutes after antigen challenge there was a marked increase of PGD2 (p < 0.01), peptide leukotrienes (p < 0.01), and 15-HETE (not significant) on both study days. However, no significant differences in the release of eicosanoids were found between furosemide and placebo groups. CONCLUSIONS: Our observations in the nasal mucosa suggest that furosemide has no effect on the release of proinflammatory and bronchoconstrictor metabolites (PGD2, peptide leukotrienes, and 15-HETE). In contrast to bronchial asthma, allergen-induced rhinitis was not effectively prevented by furosemide. PMID- 8349936 TI - Receiver operating characteristic analysis: a useful method for a comparison of the clinical relevance of two in vitro IgE tests. AB - BACKGROUND: The objectives of this study were to demonstrate the usefulness of Receiver Operating Characteristic (ROC) analysis in the definition of a positive threshold in the comparison of two in vitro tests for detecting IgE antibodies and to determine the clinical relevance of specific IgE tests according to the sensitivity and specificity determined by ROC analysis. METHODS: Specific IgE levels were compared with the use of both MATRIX (Abbott Laboratories, Chicago, Ill.) and PHADEZYM (Pharmacia, Uppsala, Sweden) tests in 109 patients: 86 allergic patients and 23 control subjects. All allergic patients had a clinical history of allergy to mite, cat, grass pollen, or birch pollen and positive skin prick test results to the suspected allergen. Using various levels of specific IgE, we determined the points of the ROC curves with the best ratio of true positives to false positives for four aeroallergens (i.e., mite, cat, grass pollen, and birch pollen). RESULTS: Except for mite allergen there was no correspondence between the positive threshold values determined by ROC analysis with MATRIX and PHADEZYM tests. In terms of class, when ROC analysis was used, the threshold was class III with the MATRIX test and class II with PHADEZYM test for cat, grass pollen, and birch pollen and class III for mite. According to the threshold value, sensitivity and specificity for MATRIX and PHADEZYM tests were similar except for cat, for which the PHADEZYM test had a lower sensitivity (0.71) than the MATRIX test (0.90). With mite allergen the predictive value of only one positive MATRIX test result was 0.96. The specificities of MATRIX and PHADEZYM tests were 100% in both nonatopic and atopic control groups. CONCLUSIONS: We conclude that ROC analysis is a reliable method for comparing IgE in vitro tests and that it emphasizes the lack of correspondence between arbitrary units given for each in vitro test. ROC analysis appears to be a good method for helping to standardize IgE in vitro tests. PMID- 8349937 TI - Diagnostic tests in enzyme allergy. AB - BACKGROUND: Allergies to enzymes occur frequently in enzyme manufacturing plants. In epidemiologic studies the number of exposed subjects with symptoms is considerably higher than the number of sensitizations as assessed by skin tests or RAST. It was the aim of this study to evaluate the sensitivity and specificity of skin prick tests, enzyme allergosorbent test, and immunoprint with enzymes by using the results of bronchial provocation tests as the "gold standard." METHODS: We performed 82 bronchial provocation tests with nine different enzymes in 42 chemical plant workers, all of whom had reported work-related symptoms. All tests with the exception of bronchial provocation tests were also performed in 10 atopic and 10 healthy control subjects. RESULTS: Thirteen workers showed positive results to bronchial provocation tests (50% or greater fall in specific airway conductance) with an enzyme at a maximal concentration of 10 mg/ml. Equivocal test results, that is, tests with a 30% or greater and less than 50% fall in specific airway conductance were seldom. Skin prick tests with nondialyzed aqueous enzyme extracts at a concentration of 10 mg/ml yielded a sensitivity of 100% and a specificity of 93%. Control subjects had no cutaneous reactions to enzymes. Discrepancies between skin tests and bronchial provocation tests occurred in 5 of 82 tests, all with a positive skin test and a negative bronchial provocation test. False-positive skin tests were considered more likely in four subjects and a false-negative bronchial challenge more likely in one case. Enzyme allergosorbent test was 62% sensitive and 96% specific, and atopic control subjects showed positive results in two cases. Results of immunoprint with amylase showed one main band at pH 3.4; this band was also found in exposed subjects without further signs of sensitization, but was not found in control subjects. All but one person with positive results to bronchial provocation tests with enzymes showed bronchial hyperresponsiveness. We identified 13 subjects with bronchial hyperresponsiveness, but without occupational allergy: five of these had sensitizations to nonoccupational allergens and the remainder showed bronchial hyperresponsiveness without any detectable cause. CONCLUSIONS: Occupation-related symptoms were not indicative of occupational allergy. Bronchial provocation tests and skin prick tests with nondialyzed aqueous enzyme extracts were appropriate techniques for the diagnosis of enzyme allergy. PMID- 8349938 TI - Nasal cholinergic hyperresponsiveness in atopic subjects studied out of season. AB - BACKGROUND: Atopic individuals have previously been shown to have an autonomic imbalance consisting of heightened cholinergic responsiveness in the lung, skin, and eyes, and beta-adrenergic hyporesponsiveness in the lungs, eyes, and vasculature. This array of abnormalities is often accompanied by nonspecific bronchial hyperresponsiveness, as well as alpha-adrenergic hyperresponsiveness in individuals with asthma. METHODS: To determine whether atopic individuals have intrinsic nasal airway hyperresponsiveness to methacholine, 21 nonatopic subjects and 37 subjects with allergic rhinitis were studied. All subjects were studied out of their allergy seasons, and all allergy-related medications were discontinued before the study began. Subjects underwent nasal challenge with methacholine (1 to 25 mg), and lavaged nasal secretions were analyzed for total protein, the plasma marker albumin, and the glandular marker lactoferrin. RESULTS: Atopic subjects demonstrated increased glandular responsiveness to methacholine as evidenced by an increase in the secretion of lactoferrin in response to individual doses of methacholine. Although the maximal lactoferrin secretion did not increase, glandular sensitivity to methacholine was heightened because the dose of methacholine required to induce lactoferrin secretion achievable by 60% of the study population was significantly lower in the atopic group. The volume of lavaged secretions recovered and congestion scores were also higher in the atopic group as compared with the normal control group. CONCLUSIONS: These data strongly suggest that atopic individuals have intrinsic nasal glandular hyperresponsiveness to cholinergic stimulation. PMID- 8349939 TI - Relative potencies and time course of changes in adenosine 5'-monophosphate airway responsiveness with inhaled furosemide and bumetanide in asthma. AB - A randomized, double-blind, placebo-controlled study was conducted to compare the effects of two chemically unrelated "loop" diuretics, furosemide (40 mg) and bumetanide (2 mg) on the bronchoconstrictor response to inhaled adenosine 5' monophosphate (AMP) in 12 subjects with asthma. In eight additional volunteers with asthma, we also carried out a separate randomized, double-blind study to examine in more detail the time course of change in bronchial reactivity to inhaled AMP after administration of nebulized furosemide and bumetanide. Inhaled loop diuretics significantly increased the provocative concentration of AMP causing a 20% fall in forced expiratory volume in 1 second (FEV1) from the value of 21.2 mg/ml (range, 2.5 to 96.9 mg/ml) after placebo administration to 83.4 mg/ml (range, 11.3 to 345.0 mg/ml) (p < 0.01) and 33.8 mg/ml (range, 4.7 to 120.9 mg/ml) (p < 0.05) after administration of furosemide and bumetanide, respectively. After placebo administration, the provocative concentration of AMP causing a 20% fall in FEV1 (PC20 AMP) at 10, 30, and 120 minutes did not differ significantly; their geometric mean (range) values were 57.8 mg/ml (10.9 to 341.0 mg/ml), 55.0 mg/ml (13.2 to 304.1 mg/ml), and 52.8 mg/ml (14.4 to 252.2 mg/ml), respectively. When compared with placebo, inhaled furosemide significantly reduced the airway responsiveness to AMP at all time points; the PC20 AMP values at 10, 30, and 120 minutes were 154.6 mg/ml (29.4 to 658.7 mg/ml) (p < 0.01), 142.6 mg/ml (25.5 to 639.9 mg/ml) (p < 0.01), and 103.9 mg/ml (12.5 to 605.5 mg/ml) (p < 0.05), respectively. The PC20 values for AMP after pretreatment with bumetanide were significantly increased up to 110.2 mg/ml (25.9 to 639.0 mg/ml) (p < 0.01) and to 92.0 mg/ml (21.6 to 531.7 mg/ml) (p < 0.05) at 10 and 30 minutes, respectively. At 120 minutes, inhaled bumetanide failed to affect AMP airway responsiveness; the PC20 AMP was not significantly different from that of placebo, with a value of 71.5 mg/ml (22.6 to 318.0 mg/ml). We conclude that comparable equidiuretic doses of furosemide and bumetanide are effective in attenuating the airway response to AMP, with furosemide being approximately 2.5 times more potent than bumetanide (p < 0.01). The time course of change in bronchial reactivity to AMP is similar for both drugs with a peak effect at 10 minutes. It is possible that the mechanism(s) underlying the protective effects of inhaled loop diuretics in asthma may be distinct from those responsible for their diuretic properties. PMID- 8349940 TI - Analysis of rat urine proteins and allergens by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. AB - BACKGROUND: In rats, urine has been identified as a major source of the allergens that cause laboratory animal allergy, an important occupational health problem. METHODS AND RESULTS: Urinary proteins and allergens of Wistar rats were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Proteins excreted by male and female rats during puberty were similar and of low molecular weight. In adulthood, moderate increases in diffuse staining of 26 and 21 kd occurred in female urine. In males the 17 kd protein increased dramatically and the 23 and 21 kd proteins moderately. The urine excretion of high-molecular weight proteins (75 to 63 kd) increased with age in males (females not studied). Immunoblot studies with six sera showed allergens in urine of male and female rats of all ages, three of which were present in all urine (75, 68, and 21 kd). Three allergens (17, 16, and 15 kd) in female urine may be allergenically similar to the 17 kd allergen in adult male urine. Adult male urine allergens were studied further with sera from 83 rat-hypersensitive subjects. Major allergens were identified at 23, 21, and 17 kd, and all sera had IgE to one or more of these proteins. Twenty-seven percent had IgE to 68 and 63 kd allergens. Minor allergens were identified at 75, 51, and 44 kd. CONCLUSIONS: Rat urine is an important source of the major allergens associated with rat hypersensitivity. Age and sex markedly influence the protein and allergenic constituents of rat urine. PMID- 8349941 TI - Basidiospore allergen release: elution from intact spores. AB - BACKGROUND: We sought to test the hypothesis that allergens are readily released by intact basidiospores in vitro and that different species release allergens in different patterns that are related to spore wall structure. METHODS: To assess basidiospore allergen releasability, basidiospore allergens were extracted from disrupted spores and eluted from intact spores, and the allergenic potency of the extracts and eluates was compared in Calvatia cyathiformis, Psilocybe cubensis, Lentinus edodes, and Pleurotus ostreatus. RESULTS: There was a significant species difference; on the basis of dry weight, the yield of extract and eluates from P1. ostreatus greatly exceeded the yield from C. cyathiformis extract and eluates. As measured by RAST inhibition, the allergenic potency of P1. ostreatus and L. edodes spore eluates reached the potency of disrupted spore extract in less than 4 hours. Allergen potency of Ps. cubensis and C. cyathiformis eluate approached the potency of disrupted spore extract only after 8 and 24 hours. Allergen staining intensity in sodium dodecyl sulfate polyacrylamide gel electrophoresis IgE immunoblot correlated with RAST activity. C. cyathiformis and Ps. cubensis spores have thick walls, whereas P1. ostreatus and L. edodes spore walls are thin and hyaline (nonpigmented). Thus spore allergen release may relate to spore wall characteristics. CONCLUSIONS: These studies indicate that intact basidiospores of all four species release allergens, but the release patterns differ by species, and these differences may be clinically significant. PMID- 8349942 TI - Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. AB - BACKGROUND: We have examined whether the local eosinophilia provoked by inhalational allergen challenge of patients with atopic asthma is associated with the appearance, in vivo, of activated TH2-type T helper lymphocytes. METHODS: Fifteen patients with atopic asthma had bronchial wash and bronchoalveolar lavage (BAL) 24 hours after allergen or diluent challenge separated by at least 21 days. RESULTS: There was an increase in eosinophils in both bronchial wash (p = 0.01) and BAL (p = 0.02) after allergen challenge but not after diluent challenge. Activation of CD4+ BAL T cells was suggested by an increase in the expression of CD25 shown by flow cytometry after allergen challenge, when compared with diluent (p = 0.02). There was no evidence of activation of CD8 T cells. By in situ hybridization after allergen challenge as compared with diluent, increases were shown in the numbers of cells expressing mRNA for interleukin-4 (IL-4) (p = 0.005), IL-5 (p = 0.01), and granulocyte-macrophage colony-stimulating factor (p = 0.03) but not IL-3, IL-2, or interferon-gamma. In situ hybridization of BAL cells after immunomagnetic separation of CD2-positive and CD2-negative cell populations showed that IL-4 and IL-5 mRNAs were associated with T lymphocytes after allergen challenge. BAL and bronchial wash eosinophilia closely correlated with maximal late fall in forced expiratory volume in 1 second after allergen challenge. CONCLUSION: Cytokines produced by activated TH2-type CD4+ T cells in the airway may contribute to late asthmatic responses by mechanisms that include eosinophil accumulation. PMID- 8349943 TI - Defective interleukin-2 and interferon-gamma gene expression in response to antigen in a subgroup of patients with common variable immunodeficiency. AB - Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestations of the disease and in the underlying mechanisms leading to the immunodeficiency. The impairment of B-cell function can be due to an intrinsic defect of the B cells, a deficiency in the function of the antigen presenting cell, or a dysfunction in the course of T-cell activation. In the present report we have focused our attention on T-lymphocyte activation in three patients with CVID. Numbers of T and B cells, as well as CD4 and CD8 T cell subsets, were within the normal range. The patients' B cells secreted IgM but did not secrete IgG and IgA in response to B-cell stimuli in vitro. Addition of allogeneic T cells was followed by an increase in IgM production but had no effect on the other immunoglobulin isotypes. Examination of T-cell function revealed impaired proliferative response, interleukin-2 (IL-2) and interferon gamma gene expression and IL-2 release after antigenic stimulation, whereas T cell proliferation, as well as IL-2 gene expression and release in response to stimulation via anti-CD3, were comparable to those of healthy control subjects. Anti-CD3-induced IFN-gamma gene activation in T cells from two patients was comparable to that of control subjects, whereas T cells from the third patient showed reduced expression of IFN-gamma mRNA. In contrast to the decreased IL-2 and IFN-gamma mRNA levels, IL-2R transcripts examined in parallel were normal in CVID T cells on stimulation with antigen. The defect in IL-2 and IFN-gamma mRNA expression after stimulation with antigen, but not with anti-CD3, suggests an abnormality confined to T-cell activation by the T-cell receptor. PMID- 8349945 TI - Reduction of allergic reactions in patients undergoing long-term hemodialysis. PMID- 8349944 TI - Therapy for patients with recurrent infections and low serum IgG3 levels. PMID- 8349946 TI - Anaphylaxis to latex in intravenous fluids. PMID- 8349947 TI - Effects of acetate on human immune system. AB - The immunopharmacologic effects of Ringer's acetate on healthy persons and cancer patients were investigated. Enhancement of in vivo polyclonal antibody production in peripheral blood lymphocytes from healthy subjects and cancer patients was elicited after the intravenous administration of 500 ml Ringer's acetate solution. Allogeneic mixed lymphocyte reaction(MLR) and natural killer(NK) activity were also increased in the majority of healthy individuals and cancer patients when administered Ringer's acetate solution but not Ringer's lactate solution. PMID- 8349948 TI - In vitro and in vivo comparative studies on immunosuppressive properties of cyclosporines A, C, D and metabolites M1, M17 and M21. AB - Cyclosporine A (CsA) and its major metabolites: M1, M17 and M21 and two analogues: cyclosporines C (CsC) and D (CsD), were studied for their capacity to interfere with different in vitro activation pathways. Their inhibition potentials against the reaction of Graft-versus-Host (GvH) were also studied. The results showed: CsA, CsC and metabolite M17 were the most active compounds upon the inhibition of lymphocyte proliferation induced by different mitogens (ConA, PHA, PWM) and also on the proliferation of mixed lymphocyte cultures (MLC). The same results were observed concerning the direct activation by protein kinase C using a combined action of phorbol ester + calcium ionophore. In vivo using local GvH reaction, CsA and CsC proved more active than M17 in the two different combinations: H-2d --> (H-2b x H-2d)F1 and H-2k --> (H-2b x H-2k)F1 CsD and two metabolites M1 and M21 showed no or weak immunosuppressive effects. Overall, the immunosuppressive potency of six compounds could be schematized as: CsA > or = CsC > M17 > M1 > or = CsD > M21. PMID- 8349949 TI - Inhibition of interleukin 2 driven proliferation of mouse CTLL2 cells, by selected carbamate and organophosphate insecticides and congeners of carbaryl. AB - The anticholinesterase (antiCHE) insecticides, a large family of pesticides used extensively throughout the world, inhibit serine hydrolases by carbamylating or phosphorylating a serine residue at the catalytic site. These insecticides are viewed as potential inhibitors of serine hydrolase-dependent immune functions including interleukin 2 (IL2) signalling. Previous studies in our laboratory have demonstrated that carbaryl (an antiCHE insecticide) produces a marked concentration-dependent inhibition of IL2 driven 1) proliferation of mouse CTLL2 cells, 2) proliferation of human natural killer (NK) cells, and 3) enhancement of target cell killing by human NK cells. In the present study, we examined the potential of 8 antiCHE insecticides (4 carbamates and 4 organophosphates) to inhibit IL2-dependent proliferation of mouse CTLL2 cells. The order of potency for T cell inhibition was carbaryl = dichlorvos > methiocarb > carbofuran > paraoxon > mevinphos > aldicarb = monocrotophos. In view of the relatively high inhibitory potency of carbaryl (a carbamate with low cholinergic toxicity), 3 metabolites and 5 congeners of carbaryl were tested for potency to inhibit CTLL2 proliferation. The data indicate a significant contribution of the 1-naphthol leaving group to inhibition of T cell proliferation by carbaryl, and are consistent with inhibition of a serine hydrolase(s) as a mechanism contributing to the observed inhibition of IL2-dependent proliferation. PMID- 8349950 TI - The effect of two glucan carboxymethyl derivatives with various substitution degrees on cyclophosphamide immunosuppression in mice. AB - Carboxymethylglucan (CMG) in two different degrees of substitution of carboxymethyl groups (0.56 and 0.89) was administered to cyclophosphamide (CY) treated (200 mg/kg) C57B1/6 mice in three doses (10, 50, and 100 mg/kg) 24 h after CY. The influence of CMG administration on the cell suppression caused by CY was observed in the subsequent days. The cellularity of spleen, bone marrow and peripheral blood was quantified on days 2, 5, 8, 11, 15, and 21 after CY treatment. CY treated mice developed a significant decrease in peripheral blood cell counts, and spleen and bone marrow cellularity during the initial 5 days, followed by recovery in the next 15 days, with an overshoot reaction in spleen cellularity and erythrocyte levels. The initial cellularity depression and the following recovery was modified by both carboxymethyl derivatives of glucan. Cyclophosphamide treated mice exhibited less pronounced immunosuppression and more rapid hematopoietic recovery when administered with CMG, although this reaction was only of a modest degree. The effects were not dose dependent and the differences between the two glucans were not significant. PMID- 8349951 TI - Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes. AB - The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10(-4)mol/l, ketanserin at 10(-4) and 10(-8)-10(-10)mol/l and methiotepine at 10(-4) and 10( 6)-10(-8)mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration. PMID- 8349952 TI - Enhancement of immunoglobulin A production in Peyer's patches by oral administration of a traditional Chinese medicine, xiao-chai-hu-tang (Shosaiko to). AB - The Peyer's patches contain a large number of precursor cells committed to the production of immunoglobulin A (IgA) and play an important role in IgA response in the mucosal immune system. We investigated the induction of IgA producing cells in Peyer's patches by plaque forming cell assay after oral administration of a traditional Chinese herbal medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to). The number of total IgA producing cells in the Peyer's patches detected by the protein-A plaque assay was increased about two-fold by Shosaiko to administration and the numbers of both anti-SRBC and anti-HRBC IgA producing cells were also increased by such a treatment. On the other hand, when SRBC alone were administered orally, only the number of anti-SRBC IgA producing cells was increased. Further, we examined T-cell subpopulations in the gut-associated lymphoid tissues after oral administration of Shosaiko-to by flowcytometry. Marked alternations in T cell subpopulations were not detected in the Peyer's patches, though TcR gamma delta+T-cells in the intraepithelial lymphocytes and Thy1.2-TcR alpha beta+T cells in the mesenteric lymph nodes were slight increased. These results showed that orally administered Shosaiko-to acts as a polyclonal B-cell activator which induces IgA production in the mucosal immune system. PMID- 8349954 TI - Influence of arecoline on immune system: III. Suppression of B cell-mediated immune response in mice after short-term exposure. AB - Arecoline, a major alkaloid of arecanut was examined to explore its modulatory influence on B cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at sub-toxic concentrations of arecoline. The number of primary antibody forming cells (AFC) and hemagglutinating and hemolysis antibody titers to Sheep Red Blood Cells (SRBC) were evaluated in male mice. Arecoline exposure for a week invoked dose-dependent effect on primary antibody forming cells to SRBC with a maximum reduction at the dosage of 20 mg/kg bw, a moderate reduction at 10 mg/kg bw and no effect at 5 mg/kg bw dose level. HA and HL antibody titers to SRBC were suppressed markedly at arecoline dosage of 20 mg/kg bw and moderately at a dose of 10 mg/kg bw, given daily for 1, 2 or 3 weeks. The inhibitory effect of arecoline was not dependent on the duration of treatment. Like the primary antibody response, the secondary HA and HL antibody titers were also decreased after arecoline exposure. The administration of arecoline dosages 10 and 20 mg/kg bw daily for 4 days following SRBC immunization also, exerted dose-dependent suppression of primary antibody response. Similarly, when treated after 12 h following immunization, significant reduction in response was observed with arecoline dosage of 20 mg/kg bw. While moderate suppression of antibody response was noticed at the dose level of 10 mg/kg bw, there was no alteration in response at a dosage of 5 mg/kg bw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349953 TI - Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content. AB - The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl2 as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl2 for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constant, or increased following exposure to mercury. GSH levels were also reduced in monocytes following exposure to HgCl2; in this case, GSSG levels remained constant and a decline in the GSH/GSSG ratio was observed. For all cell types, mercury did not inhibit the activities of GSH reductase and GSH peroxidase, enzymes responsible for oxidation/reduction of GSH and GSSG, respectively. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8349956 TI - Meetings on endocrinology at Pisa, 28-29 June 1993. Abstracts. PMID- 8349955 TI - Triazolobenzodiazepines exert immunopotentiating activities on normal human peripheral blood lymphocytes. AB - Previous studies have demonstrated that benzodiazepines (BDZ) (e.g. diazepam) inhibit immune responsiveness. Since these drugs are largely used in psychiatric patients it is of great importance to verify the existence of different types of BDZ, which are not suppressive for the immune system. In this framework, our results indicate that alprazolam and triazolam, two triazolo-BDZ, do not modify in vitro phagocytosis and killing exerted by normal human polimorphonuclear cells and monocytes. On the contrary, they significantly enhance T lymphocyte-dependent antibacterial activity in normal donors. These data support the concept that triazolo-BDZ and, in particular, alprazolam may represent more appropriate drugs for the treatment of psychiatric patients (e.g. patients with phobic disorders and/or migraine) who display immunodeficits. PMID- 8349957 TI - 21st annual meeting of the European Thyroid Association. Cardiff, Wales, U.K., July 4-9, 1993. Abstracts. PMID- 8349958 TI - Hand surgery and the medical liability issue. PMID- 8349960 TI - Dislocation of the distal phalanx epiphysis in toddlers. AB - Two cases of physeal fracture dislocation of the distal phalanx are reviewed. Each injury occurred in a toddler, was originally undiagnosed, and appeared years later as a dorsal mass in a fore-shortened digit with decreased distal interphalangeal joint motion. In each case x-ray films revealed a dislocated epiphysis, accounting for the enlarging dorsal prominence and the phalangeal growth disturbance. These cases demonstrate that dislocation of the distal phalanx epiphysis can occur with a crush injury and may be difficult to detect before development of the ossification center. Careful physical examination and a high index of suspicion will increase the likelihood of early diagnosis. Early open reduction may prevent the late complications of deformity and stiffness. PMID- 8349959 TI - Niebauer trapeziometacarpal arthroplasty: a long-term follow-up. AB - A retrospective review of long-term follow-up of Niebauer trapeziometacarpal arthroplasty for treatment of disabling arthritis of the basal joint was performed. Thirty implants in 27 patients were reviewed, with an average follow up of 9 years (minimum, 4 years). All surgical procedures were performed by the senior author. Eighty-eight percent of the patients were subjectively pleased and would undergo the procedure again. Postoperative subluxation occurred in 83% of the patients. This was not painful unless the prosthesis dislocated. Subluxation increased with time. One case of silicone synovitis necessitated implant removal; however, this was also after removal of a previous Eaton prosthesis. In the light of our results, we believe that the Niebauer trapeziometacarpal arthroplasty is a worthwhile procedure with a rare incidence of particulate synovitis. In 24 of 27 patients, pain was relieved and satisfactory motion and stability were achieved. PMID- 8349961 TI - Bilateral os centrale carpi: a rare congenital variant. PMID- 8349962 TI - Magnetic resonance imaging to visualize the internal anatomy in the Baller-Gerold syndrome. AB - The Baller-Gerold syndrome is identified by radial aplasia with craniosynostosis. Only 12 cases have been reported previously in the literature; none of the reports describe surgical treatment for the radial aplasia. We report the case of a 10-month-old female infant with this syndrome, including severe bilateral radial clubhands. A radial anlage, which was tethering growth of the ulna, was suspected on physical examination and confirmed with magnetic resonance imaging. Resection of the anlage resulted in dramatic improvement in elbow extension, but additional follow-up will be necessary to determine the complete functional effect of the procedure. PMID- 8349963 TI - Acute calcific tendinitis in a child: a case report. PMID- 8349964 TI - Distal unicondylar fractures of the proximal phalanx. AB - The records of 38 consecutive patients (38 fractures) who underwent treatment for distal unicondylar fractures of the proximal phalanx were reviewed to evaluate fracture characteristics, mechanism of injury, treatment options, and functional outcomes. Four classes of fracture pattern were defined radiographically. Most fractures occurred during ball sports and involved an axial splitting of extended digits, with the condyle closet to the midline of the hand fracturing most commonly. We believed that the fracture occurred as a result of tension loading due to a distraction force from the collateral ligament. All fractures healed. Follow-up examination averaged 3 years. Five of seven nondisplaced fractures treated with splinting and four of ten displaced fractures treated with reduction and single Kirschner wire fixation displaced. Fractures treated with multiple Kirschner wire fixation had the best final joint motion. Class IV fractures with a small palmar coronal fragment had the poorest final motion. A short period of post-operative immobilization did not adversely affect final proximal interphalangeal joint motion. We recommend multiple Kirschner wire or miniscrew fixation of these fractures as the most predictable method of treatment. Final proximal interphalangeal joint motion is not uniformly excellent in patients with these fractures. PMID- 8349965 TI - Biomechanical analysis of mallet finger fracture fixation techniques. AB - A biomechanical study was conducted to determine the best fixation technique for mallet finger fracture among four commonly used methods. Considerations were technical complications, biomechanical properties, and maintenance of reduction. Techniques tested included Kirshner wire, figure-of-eight wire, tension band wire, and tension band suture. Technical complications were frequent with both the Kirschner wire and tension band wire techniques. Biomechanical testing yielded significantly greater energy absorbed to failure and a trend toward greater peak loads to failure for both the figure-of-eight wire and tension band suture techniques. Irreversible loss of reduction during testing occurred in all of the Kirschner wire-fixed fractures, in 60% of the tension band wire-fixed fractures, and in 50% of the figure-of-eight wire-fixed fractures. No irreversible failure occurred in the tension band suture group. PMID- 8349966 TI - Primary non-Hodgkin's lymphoma presenting in the upper extremity: a case report. PMID- 8349967 TI - Treatment and prevention of "hook nail" deformity with anatomic correlation. AB - The hook nail deformity is a relatively common complication after fingertip amputation. It can be corrected or prevented with a carefully performed surgical procedure. The nail plate is removed. The redundant nail bed that is folded over the tip of the terminal phalanx is carefully removed with an additional 2 mm that is supported by the terminal phalanx so that wound healing will not draw the nail bed over the tip of the phalanx again. The fingertip is then resurfaced by a V-Y advancement flap, with precautions taken to avoid all tension in the flap. PMID- 8349968 TI - Color flow Doppler: imaging the upper extremity. AB - Dynamic values of key vessel diameter, blood velocity, and flow rate in the upper extremity were obtained in 20 healthy volunteers by means of color flow Doppler imaging with a 7.5 MHz transducer. Recordings were made of the brachial, radial, posterior radial recurrent, ulnar, and digital arteries. Radial and ulnar vessels were evaluated at both wrist and midcarpal levels. Diameter and velocity changes were followed throughout the cardiac cycle, and a true mean flow was computed. Mean diameters of the digital vessels ranged from 0.9 mm in the small finger to 1.3 mm in the thumb. Brachial flows ranged from 4.6 to 89.9 ml/min, radial flows from 0.9 to 15.3 ml/min, and ulnar flows from 0.6 to 79.9 ml/min. At the midcarpal level, flows ranged from 0.2 to 68.4 ml/min for the ulnar artery and from 0.8 to 42.9 ml/min for the radial artery. Variability between individuals was also demonstrated in artery dominance: eleven ulnar dominant, seven radial dominant, and two equal (within 25% of each other). The accuracy and ease of use of this technique in measurement of vessels are limited when vessels are less than 1.5 mm in diameter although the technique provides quantitative values to 0.5 mm. PMID- 8349969 TI - Radial and ulnar artery repairs: assessing patency rates with color Doppler ultrasonographic imaging. AB - This study was undertaken to evaluate the patency rate of radial and ulnar artery repairs performed with use of the magnification afforded by the operative microscope. Color Doppler ultrasonographic imaging was chosen as a reproducible, noninvasive technique to evaluate patency and graphically display vascular flow characteristics. Twenty-eight consecutive patients with 35 arterial injuries form the study group. Twenty-four patients with 31 arterial lacerations were available for enrollment in the protocol. Follow-up ranged from 1 to 40 months (average, 10 months). Eighteen male and six female patients sustained 13 radial and 18 ulnar artery lacerations, all sharp. Four patients required interposition vein grafting. Overall patency after repair was found to be 84%, with 82% of single vessels and 86% of double vessels patent. The patency of single vessels repaired without the use of vein grafts was 100%. These results indicate that microscope assisted repairs of the radial and ulnar arteries remain patent at a higher rate than is commonly cited. PMID- 8349970 TI - Ex vivo perfusion with anticoagulated blood decreases ischemia/reperfusion injury. AB - Rat muscle flaps (cutaneous maximus) were subjected to 4 hours of room temperature ischemia followed by 44 hours of cold (4 degrees C) ischemia before transplantation. Experimental flaps underwent a 15-minute ex vivo perfusion with heparinized-citrated blood between the warm and cold ischemic treatments; control flaps were not perfused. After 1 or 48 hours of recirculation, muscle dehydrogenase activity was found to be higher in the perfused flaps, indicating better muscle viability. Lipid peroxidation was lower in the perfused flaps, indicating a reduction in free radical generation. Histologic assessment revealed that perfused flaps underwent less injury than unperfused flaps. The findings of this study indicate that replacement of standing blood with anticoagulated blood, with the use of a brief ex vivo perfusion protocol, has a significant protective effect against ischemic injury. The experimental design mimics a realistic point of intervention and presents a paradigm for the clinical treatment of amputated extremities. PMID- 8349971 TI - Evaluation of sympathetic control of digital blood flow. AB - A noninvasive strain-gauge method of measuring blood flow in the digit was used to assess the influence of the sympathetic system in the digit. The sympathetic system was stimulated by the sudden application of ice to the neck, thus avoiding in the hand local reflexes and responses to cold. Seventeen normal subjects responded in similar fashion. Maximum flow reduction ranged from 26% to 92%, with a mean of 61%. This method should be useful diagnostically and for research when sympathetic reactivity, in contrast to basal sympathetic tone, needs to be determined. PMID- 8349972 TI - Sonographic evaluation of pseudoaneurysm of a digital artery: a case report. PMID- 8349973 TI - The functional significance of the long extensors and juncturae tendinum in finger extension. AB - To determine the role of the long extensors and soft tissues in the extension and interaction of the fingers, we applied traction to the extensors and measured the angles of the finger joints. The tendons, juncturae tendinum and intertendinous fascia, and the web between the fingers were sequentially sectioned, and the effects on the joints were again determined with tendon traction. Traction produced hyperextension of the metacarpophalangeal joints and some extension of the interphalangeal joints, although the latter remained partially flexed, producing a clawhand. Cutting the long extensor tendons had no effect on the interaction between adjacent fingers. Traction on the extensor digitorum communis to the index and the extensor indicis proprius produced the same extension of index finger joints and adjacent digits. Traction on the extensor digitorum communis to the index produced 32% of the maximal extension of the long finger MP joint. We reduced this to 22% by cutting the juncturae and intertendinous fascia and to 5% by cutting the web. The interaction between fingers was greater on the ulnar half of the hand because of the juncturae but was similarly reduced by ablative cuts of these structures. PMID- 8349974 TI - Extensor pollicis longus rupture at the tip of a prominent fixation screw: report of three cases. AB - Rupture of the extensor pollicis longus tendon at the tip of a prominent fixation screw occurred in two cases after fixation of fractures of the radial shaft and in one case after fixation of a fracture of the scaphoid. Patients were referred because of their inability to extend the thumb. Active thumb extension was restored in two patients by screw removal and tendon transfer. The third patient elected nonoperative care. Close scrutiny of good-quality intraoperative x-ray films after internal fixation about the wrist may detect screws that are too prominent and thereby prevent rupture of the extensor pollicis longus tendon. PMID- 8349975 TI - Factors affecting results after flexor tendon repair in zone II: a multivariate prospective analysis. AB - A stepwise multiple regression procedure was used to examine the influence of 12 to 13 independent variables on five outcome variables, 1 year after flexor tendon repair in zone II, in a consecutive series of 135 patients treated with early controlled motion. Of the included variables, controlled interphalangeal joint range of motion 3 weeks postoperatively was the single most influential factor with regard to final active interphalangeal joint range of motion. Together with age, swelling, the number of digits, and the number of tendons injured, it accounted for 18% to 19% of the total variance in active range of motion; 14% to 15% of the variance in extension deficits and 41% of the variance in grip strength could be accounted for by variables included in the study. A large part of the variance in all the outcome variables was probably related to the psychological and biologic characteristics of the patient. PMID- 8349976 TI - Osteoblastoma of the scaphoid: a case report. PMID- 8349977 TI - Intraosseous ganglion of carpal scaphoid: a case report. PMID- 8349978 TI - Acute carpal tunnel syndrome caused by tophaceous gout. PMID- 8349979 TI - The patchy configuration of scaphoid avascular necrosis. AB - The proximal poles of five patients with presumed avascular necrosis of the scaphoid, mostly the result of nonunion, were analyzed histologically for true, pathologically confirmed avascular necrosis of bone. Each specimen was reviewed both qualitatively by an experienced bone pathologist and quantitatively with the use of a computerized image analysis system. Avascular necrosis was found to be variable from one specimen to another as well as within each specimen. Midcentral levels showed a statistically significant greater degree of avascular necrosis than either adjacent palmar or dorsal zones. Both viable and nonviable areas of avascular bone were found in an unpredictable, irregular (patchy) distribution, often in direct apposition to one another. It is apparent from this study that random biopsy alone cannot accurately predict the histologic status of the entire specimen; the clinician must rely on other methods to determine scaphoid viability. PMID- 8349980 TI - Long-term follow-up of scaphoid-trapezium-trapezoid arthrodesis. AB - A series of 19 consecutive patients who underwent scaphoid-trapezium-trapezoid arthrodesis for chronic scapholunate instability or isolated arthrosis was reviewed. The average follow-up of 14 patients was 62 months. Eight of these 14 patients had significant residual symptoms and/or functional limitations at follow-up, and 11 had complications, including radiocarpal arthrosis (six patients), trapeziometacarpal arthrosis (four patients), and nonunion (three patients). Fusion without reduction of the scaphoid to a normal orientation was predictive of a poor result, but normal scaphoid positioning did not preclude development of arthrosis. Development of a painful degenerative thumb carpal metacarpal joint may occur as an isolated phenomenon after scaphoid-trapezium trapezoid arthrodesis. PMID- 8349981 TI - Asymptomatic SLAC wrist: does it exist? AB - Twenty-five patients (30 wrists) had x-ray evidence of scapholunate advanced collapse. Twenty-two wrists had no pain; 12 of these were diagnosed and treated for carpal tunnel syndrome. Eight wrists had mild pain. All patients were reevaluated an average of 2 years later. At that time, 20 wrists were totally free of symptoms and 10 had occasional pain, especially with increased activity (no patients required analgesics). No patient had undergone surgical management for the scapholunate advanced collapse. We believe that there are some patients (especially older and low-demand persons) in whom x-ray evidence of arthritis and clinical findings do not correlate. In these circumstances surgical intervention for treatment of the arthritis may not be warranted. PMID- 8349982 TI - Biomechanical analysis of radial wedge osteotomy for the treatment of Kienbock's disease. AB - Biomechanical analysis of force transmission through the lunate was performed with the use of a two-dimensional mathematical model to evaluate the usefulness of radial wedge osteotomy, a procedure that decreases radial inclination, in the treatment of Kienbock's disease. The forces acting on the carpal bones were compared before and after radial wedge osteotomy in 29 patients with Kienbock's disease. The average osteotomy angle was 9.6 degrees. The total force through the lunocapitate joint at the midcarpal level was decreased by 23%, while the total force through the radiolunate and ulnolunate joints at the radioulnocarpal level was decreased by 10% and 36%, respectively. These changes correlated directly with the osteotomy angle and demonstrate decompression of the lunate by radial wedge osteotomy. PMID- 8349983 TI - Preoperative factors and outcome after lunate decompression for Kienbock's disease. AB - Preoperative factors and outcome were studied after lunate decompression for Kienbock's disease. Twenty-three patients treated with radial shortening or scaphoid-trapezium-trapezoid fusion were evaluated. The mean follow-up was 59 months. Neither good nor excellent outcomes were found with either lunate preserving procedure when the preoperative radioscaphoid angle was greater than 60 degrees. Outcomes in the radial shortening osteotomy group were superior to those in the group treated with scaphoid-trapezium-trapezoid fusion. Lunate collapse was not prevented by either treatment method. Lunate index, carpal height, and staging did not correlate with outcome. Measurement of radioscaphoid angle provides predictive information regarding the outcome of stage III (Decoulx/Lichtman) Kienbock's disease treated with radial shortening or scaphoid trapezium-trapezoid fusion. PMID- 8349984 TI - A modified extensor carpi ulnaris tenodesis with the Darrach procedure. AB - Fourteen patients with pain and limited forearm rotation were treated with a modified Darrach procedure involving a distally based slip of the extensor carpi ulnaris tendon. Seven patients had Colles' fractures, four had rheumatoid arthritis, and three had primary osteoarthritis of the distal radioulnar joint. Patients were assigned to one of two groups: rheumatoid arthritis or Colles' fracture/osteoarthritis. The average age was 50 years. Follow-up averaged 54 months (range, 12 to 96 months). The average amount of ulnar resection was 10 mm (range, 6 to 20 mm). In the Colles' fracture/osteoarthritic group, average grip strength (a percentage of the uninvolved hand) improved from 26% preoperatively to 74% postoperatively, and in the rheumatoid arthritis group it improved from 67% to 144%. Distal ulnar instability of the dorsal side was not observed on x ray examination. Patients were satisfied with pain relief, and all returned to their original work. PMID- 8349985 TI - Treatment of posttraumatic radioulnar synostosis with excision and low-dose radiation. AB - Two cases of posttraumatic radioulnar synostosis treated with excision and low dose radiation are presented. Routine postoperative hand therapy was employed. Nearly full range of motion was restored in both cases. No wound healing problems were encountered. We suggest that low-dose radiation may be a useful method of prophylaxis against recurrence after excision of radioulnar synostosis. PMID- 8349986 TI - Intratendinous ganglia of the hand. AB - We report a series of seven patients with 10 intratendinous ganglia that were treated operatively. One ganglion was in the abductor pollicis longus tendon. The rest were in tendons of the fourth extensor compartment, and all of them were associated with tenosynovitis. The average age of the patients at operation was 55 years. One patient was treated by resection of the tendon with tendon transfer. The other patients were treated by excision of the ganglion with repair of the tendon or tenosynovectomy. The mean length of postoperative follow-up time was 6 years. One patient experienced a recurrence. Three of the six patients with preoperative dorsal tenosynovitis had tenosynovitis postoperatively. We speculate that the ganglia arose secondary to tenosynovitis. When an intratendinous ganglion is diagnosed, tenosynovectomy is recommended, with resection of the intratendinous ganglion and longitudinal tendon repair when needed. PMID- 8349987 TI - The influence of age and gender on radial height. AB - Radial height was measured on carefully standardized posteroanterior x-ray films of the wrist in 25 male and 25 female patients. The range of radial height (10 to 18 mm) was the same for both male and female patients, with slightly different means for each sex. In females the mean was at the upper limit of the previously reported range, whereas in males the mean was outside the reported range. Our results suggest that previously published measurements underestimate radial height. Inasmuch as radial height may be used in planning management of distal radial fractures, it is important to redefine these measurements. We also believe that the wide range of normal makes comparison with a noninjured contralateral wrist essential for accurate assessment of radial shortening in each individual patient. PMID- 8349988 TI - The change in ulnar variance with grip. AB - The effect of grip on ulnar variance was evaluated in 66 symptom-free wrists of 53 volunteers. Zero-rotation posteroanterior x-ray films were taken of each wrist before and after exertion of a grip force measured with a Jamar dynamometer. The volunteers were randomly divided into two groups. Group I subjects (35 wrists) were asked to exert a constant grip force of 11.3 kg. Group II subjects (31 wrists) were asked to exert a maximum grip effort, which resulted in a mean grip force of 30 kg (range, 22.8 kg to 53.6 kg). Group I demonstrated a mean increase in ulnar variance of 1.27 mm and group II showed a mean increase of 1.95 mm. The minimum increase in ulnar variance observed was 0.25 mm. The changes observed were statistically significant. The results confirm that a relative increase in ulnar variance occurs with grip. There may be an etiologic role for daily activities that involve repetitive grip and forearm rotation in development of the ulnar impaction syndrome. PMID- 8349989 TI - Anatomy of the oblique retinacular ligament of the index finger. AB - The available literature includes conflicting descriptions of the anatomy and function of the oblique retinacular ligament. We have studied this ligament in the index finger to better define its presence, configuration, points of attachment, length, and relationship to the proximal interphalangeal joint axis. Twenty fresh frozen index fingers were dissected. Five additional specimens were decalcified, mounted, sectioned transversely at 1 mm intervals and studied under the microscope. An oblique retinacular ligament was identified on the radial side of the index finger in 95% and on the ulnar side in 90% of the specimens. The radial oblique retinacular ligament was usually longer and more developed than the ulnar oblique retinacular ligament. Proximally, the ligament arose from the middle third of the proximal phalanx and the A-2 pulley whereas, distally, it inserted into the lateral extensor band with a fan-shaped expansion centered 4 to 6 mm distal to the proximal interphalangeal joint line. In 70% of the specimens, the oblique retinacular ligament was supplemented by a contribution from the proximal cruciform pulley (C-1). Histologic cross sections also confirmed the presence of the oblique retinacular ligament but not the supplemental contribution arising from the C-1 pulley. The relationship of the oblique retinacular ligament to the proximal interphalangeal joint axis is dependent on the proximal interphalangeal joint position; the ligament lies palmar to the proximal interphalangeal joint axis only when the proximal interphalangeal joint is flexed. PMID- 8349990 TI - Carpal Aspergillus osteomyelitis: case report and review of the literature. PMID- 8349991 TI - A technique for maximizing biceps recovery in brachial plexus reconstruction. AB - In 21 cadaver dissections the intramuscular anatomy of the musculocutaneous nerve and the relative relationship of the motor and sensory components of this nerve were evaluated. Nearly one half of the fibers entering the musculocutaneous nerve terminate in cutaneous receptors. We report five cases in which biceps reinnervation was performed by a surgical technique that minimizes the period of denervation by using motor nerves (medial pectoral nerves) very close to the biceps muscle. This technique also redirects the cutaneous portion (lateral antebrachial cutaneous nerve) of the musculocutaneous nerve into the biceps muscle to ensure that the motor fibers are not directed toward cutaneous receptors. PMID- 8349992 TI - Carpal tunnel syndrome: surgical and nonsurgical treatment. AB - A retrospective study was performed to evaluate treatment for carpal tunnel syndrome. Two hundred sixty-five patients were treated over a 4 1/2-year period. Only patients in whom studies showed abnormal nerve conduction (a median nerve sensory latency greater than 3.6 msec or a median distal motor latency greater than 4.3 msec) were included in the evaluation. Nonsurgical treatment consisted of patient education, wrist splinting, B vitamins, nonsteroidal anti-inflammatory medication, steroid injections, and job change or modification when possible. A follow-up history, physical examination, and repeat nerve conduction studies were performed at 3- to 9-month intervals, depending on the severity of symptoms and the degree of abnormal latencies. Surgery was performed on 77 patients and 95 hands. The remaining 188 patients were treated nonsurgically. Both surgically and nonsurgically treated patients considered the results to be satisfactory. PMID- 8349994 TI - Posterior interosseous nerve: an anatomic study of potential nerve grafts. AB - Anatomic dissection of the posterior interosseous nerve in 26 cadaver forearms was performed to assess variability in location, diameter, and branching patterns of the nerve. The purpose of our study was to determine the anatomic reliability of the posterior interosseous nerve at the distal forearm level as a potential donor nerve graft for segmental digital nerve loss. The nerve was located in a separate fascicle sheath in the deep radial aspect at the fourth dorsal compartment in all specimens. It ranged from 1 to 5 mm in diameter with one to five fascicles present (15 of 26 specimens had a single fascicle). Ten additional specimens were dissected for assessment of potential length of nerve available for grafting, and this ranged from 5 to 10 cm. These nerves were believed to be of sufficient diameter for grafting of digital-level nerve injuries. There is minimal morbidity when a donor graft is obtained in the same limb as the recipient area, and there is no known donor deficit as a result of posterior interosseous nerve procurement at wrist level. PMID- 8349993 TI - Recurrent carpal tunnel syndrome due to tuberculoid leprosy in an Asian immigrant. PMID- 8349995 TI - Is this scapholunate joint and its ligament abnormal? AB - There is confusion in the literature with respect to evaluation of the scapholunate joint space and ligament. Because routine x-ray films of the wrist commonly do not profile the scapholunate joint perfectly, determination of the joint space width often is inaccurate. One method that invariably will allow a good profile of the scapholunate joint involves the use of fluoroscopically controlled views in different positions of the wrist. However, when abnormal width is suspected, in all examinations the wrist in question should be compared with the opposite wrist and the findings carefully correlated with clinical symptoms. Additional arthrographic findings, which have not been discussed in the literature before, are described. Midcarpal arthrography identifies and illustrates a variety of appearances of the scapholunate ligament. The reason for these different appearances and whether they are normal variations or pathologic findings is not known. This article is designed to stimulate further clinical and x-ray research to clarify normal and abnormal features of the scapholunate joint and ligament. PMID- 8349996 TI - The markings of the Semmes-Weinstein nylon monofilaments. PMID- 8349997 TI - Dead languages in the living hand. PMID- 8349998 TI - Aspirin and coronary artery diseases. PMID- 8349999 TI - Medical liability--international scene. PMID- 8350000 TI - Maternal deaths--a ten-year study. AB - In a 10-year retrospective study of maternal deaths at RG Kar Medical College, Calcutta there were 651 maternal deaths with 410 in first 5-year period and 241 in second 5-year period. The leading causes of deaths were due to abortion, toxaemia, haemorrhage (antepartum and postpartum) and jaundice in pregnancy. Direct causes were responsible for death in 77.6% cases, indirect causes in 17.5% cases and unrelated causes in 4.9% cases. Majority (557) were unbooked and mostly multigravida (434) cases. Most of them (251) were in the age group of 20-25 years. Haemorrhage was the single most common cause to claim 188 lives. It was also noted that 155 deaths occurred within 12 hours of hospital admission. PMID- 8350001 TI - A prospective study of closure techniques of abdominal incisions in infants and children. AB - In a prospective study of layered versus mass closure of abdominal incisions in infants and children, 34 cases underwent wound closure by layered and mass closure technique on an alternate basis. All the patients were assessed for their nutritional status and haemoglobin level pre-operatively, and wound complications were compared with respect to closure technique, nutritional status and normal haemoglobin level. Presence of protein energy malnutrition and anaemia did not increase the risk of wound complications with either of the technique. PMID- 8350002 TI - Interrelationship among prognostic factors in carcinoma breast. AB - Presentation of breast cancer at an advanced stage is a rule than exception in rural West Bengal. It was observed that 65.6% of fresh cases presented with history of breast lump with a duration of over 12 months. Of the total 32 cases, 27 (84.4%) had breast lump of more than 5 cm size and had 4 or more pathologically positive axillary nodes. In 28 cases (87.5%) largest node measured was 2 cm or more. In histology of breast specimen, 12 (37.5%) showed high degree of lymph vessel invasion while 31 (96.9%) had at least some lymphatic invasion. Blood vessel invasion of high degree was observed in 18 cases (56.2%) while 29 cases (90.6%) showed at least some blood vessel invasion. PMID- 8350003 TI - Hypertension care in general practice: an opinion survey. AB - An opinion survey was conducted among 60 general practitioners from different parts of West Bengal with 6 prefixed questions covering some practical issues of hypertension. Fifty-eight doctors responded. In the opinion of the majority, 160 mm of Hg (systolic) and 90 mm of Hg (diastolic) are the cut off pressure to diagnose hypertension. Forty-eight per cent of the practitioners opined that a period of observation is necessary before antihypertensives were started. Eighty seven per cent of the practitioners would start their patients on antihypertensive drugs well before the blood pressure reached 160/104 mm of Hg. High diastolic pressure was thought to be dangerous by 50% doctors and both high systolic and diastolic pressures were thought to be dangerous by 43% doctors. Fifty-two per cent practitioners opined that 140/90 mm of Hg should be the target blood pressure after treatment. Most of them (63%) opined that antihypertensive treatment should be continued life long. Practitioner's opinion were analysed in the light of current international literatures on basic therapeutic approaches to hypertension with emphasis on certain issues of controversy. PMID- 8350004 TI - Myelodysplastic syndrome. PMID- 8350005 TI - Rare pelvic abdominal lump--a diagnostic dilemma. PMID- 8350006 TI - Extra-uterine pregnancy following uterine conception. PMID- 8350007 TI - Shigellosis--an overview. PMID- 8350008 TI - Cataract blindness--magnitude of the problem and its management in developing country like India. PMID- 8350009 TI - Elective term: should it be a requirement for undergraduate-medical education in India? PMID- 8350010 TI - Lymphangioma circumscriptum of the vulva. PMID- 8350011 TI - Eczema/dermatitis. PMID- 8350012 TI - [Reperfusion-induced arrhythmia and oxidative stress]. AB - Although recognized and reproduced in numerous animal models, reperfusion arrhythmias were not studied extensively in humans until the advent of methods of coronary reperfusion during the acute phase of myocardial infarction. Usually of ventricular origin, these arrhythmias are polymorphic and constitute imperfect but useful markers of coronary reperfusion. Their electrophysiologic mechanisms are complex and their molecular mechanisms unelucidated. Predisposing conditions are the duration and severity of the ischemia, biochemical modifications such as heterogeneous uptake of extracellular potassium, magnesium deficit, intracellular calcium overload and release of arrhythmogenic lipid metabolites or prostaglandins. The autonomic nervous system also plays a part by an increase in the number and response of alpha-adrenoceptors. Furthermore, experimental studies provide theoretical and pharmacologic arguments for the participation of free oxygen radicals (superoxide anion (02.-, hydroxyl radical OH.) in reperfusion arrhythmias in the animal. By its complexity, human myocardial infarction differs markedly from the animal models studied; it probably involves, apart from the free oxygen radicals, multiple thrombotic, humoral and nervous factors whose respective role in the production of reperfusion arrhythmias remains to be established. Some enlightenment should be obtained by analysis of rhythmic events during proposed controlled studies using anti-free radical agents to prevent these post-myocardial infarct acute events. PMID- 8350013 TI - [Primary aorto-digestive fistulas. Four cases and review of the literature]. AB - Four cases, three fatal and one with long term recovery, of patients treated surgically for primary aorto duodenal fistulas are reported. The involved lesion was an infrarenal aortic aneurysm. Two patients had an extra-anatomic vascular procedure and two patients an in situ repair. In connection with these cases, two hundred and fifty three primary aorto enteric fistulas were reviewed in the world's literature. The difficulties in the diagnosis and treatment are pointed out. Emergency operation should be performed in all cases of gastrointestinal bleeding associated with an abdominal aneurysm. The best diagnostic approach is CT scan combined to gastro-duodenoscopy. Overall mortality in our review of the literature was seventy one per cent. Closure of the enteric component should be performed with lateral repair. Management of the aortic component remains controversial: closure of the aorta and axillo-bi femoral by pass or in situ repair. The operative mortality in our review of the literature was thirty seven per cent. Interposition of viable tissue is necessary according to the risk of recurrent infection and bleeding with consequent death (twelve per cent). So, long term control is of paramount importance. PMID- 8350014 TI - [In vitro effects of ionic and non-ionic contrast media on erythrocyte aggregation]. AB - An in vitro model was designed to examine the effect of three contrast media (CM): two non ionic (Iohexol, Iopamidol) and one ionic (Ioxaglate) molecules on erythrocyte aggregation. Red blood cells were suspended in a chemically defined medium (Albumin: 10 g/l), Immunoglobulins: 12 g/l, Fibrinogen: 1.5 g/l) supplemented with various proportions of CM (10-25% V/V). Control samples contained NaCl or Saccharose solutions with a nearly similar osmolality. Erythrocyte aggregation at constant hematocrit (HT = 40%) was determined by the analysis of the light backscattered by blood suspension during the aggregation process. As compared to control samples, non ionic CM induced a weak decrease in erythrocyte aggregation, when the ionic molecule caused a marked increase in the aggregation, which was related to CM concentration. A different interaction of ionic and non ionic CM with erythrocyte membranes has been shown by fluorescence studies. After addition of CM, it was noted a fluorescence quenching of lipophilic probes (TMA-DPH and DPH) embedded in erythrocyte membranes. This quenching probably due to benzene ring and iodine atoms of contrast media markedly varied according to the used fluorescent probe and the CM. In the presence of ionic CM, the fluorescence quenching is more important than that induced by non ionic CM. Thus, besides osmolality and viscosity of CM which play a role in erythrocyte aggregation, some intrinsic properties of CM such as the ionic or non ionic nature could influence erythrocyte membrane-contrast medium interactions and consequently erythrocyte aggregation. PMID- 8350015 TI - [Arterial thrombosis of the arm and hemorrhagic rectocolitis. Report of a case]. AB - Several cases of arterial thrombosis associated with inflammatory enterocolitis affections have been reported. In all but one case reported in the literature the outcome was favorable. A 40 year old woman developed thrombosis of the radial and ulnar arteries during an acute episode of ulcerative colitis. The course of the thrombotic lesions was irreversible and all fingers of the right hand had to be amputated. The corticotherapy as a possible predisposing factor for these thromboses is discussed, but their onset during an inflammatory episode suggests a role for the inflammatory enterocolitis. A thrombocytosis (807,000 platelets/mm3) could have predisposed to their onset, and in this case the hemostatic disturbances and fibrinolysis associated with the ulcerative colitis could have played a major role. PMID- 8350017 TI - [Pulsatile vaginal expansion: Case report of an internal iliac aneurysm detected after an injury]. AB - After a pelvic trauma, in a 78 years old women, systematic radiograms showed a polycyclic mass in the left side of the pelvis. This finding was confirmed by B mode ultrasound echography. The vaginal touch found a pulsatile and expanding mass. At surgery, the diagnosis of a fissuring aneurysm of the internal iliac artery was confirmed, and a curative treatment was undertaken. Reviewing the literature, the authors emphasize the diagnostic usefulness of rectal and vaginal touch, and the importance of an early diagnosis using noninvasive imaging techniques. Surgery is the only treatment for isolated internal iliac aneurysms. PMID- 8350016 TI - [Ehlers-Danlos syndrome type IV, revealed by a primary dissecting aneurysm of the left subclavian artery]. AB - The authors report an unusual dissecting aneurysm of the left subclavian artery occurring in a patient suffering from the Ehlers-Danlos syndrome. Clinical history and skin biopsy permitted this diagnosis. Surgical treatment associated resection of the aneurysm, ligation of the proximal part of the subclavian artery and a prosthetic bypass between carotid and subclavian artery. Spontaneous dissecting aneurysm is a rare disease and one must think before surgery to arterial dysplasia. Technical features of the surgical treatment are discussed. PMID- 8350018 TI - [Presentation of a clinical hemoviscosimeter]. AB - A clinical hemoviscosiSImeter is presented. It is a Couette type viscometer which is automatic and driven by a microcomputer. It was designed and realized in the laboratory. The measurement of blood viscosity requires 1 ml of anticoagulated blood adjusted at 45% of hematocrit. Experiments are performed at a constant temperature (37 degrees C) according to a well-established protocol: gentle mixing of the blood sample followed by a 3 minute rest just before each of the following measurement modes begins. Under steady state flow conditions, 12 viscosity measurements are realized in a range of shear stress rate step of 1 s-1 is applied. The elastothixotropic response of the blood sample is then obtained. Such a hemorheological test, called "hemorheogram", requires 15 minutes. Given to the clinician, the hemorheogram results include the absolute blood viscosities at the shear stress rates of 0.1 s-1, 1 s-1, 10 s-1, 70 s-1, the thixotropy index and the plasma viscosity. Finally, results to be kept in the laboratory files consist of the whole data issued from the patient hemorheogram including the relative blood viscosities (blood viscosity/plasma viscosity) at the same shear strers rate values. PMID- 8350019 TI - [Medical editing]. PMID- 8350020 TI - [Evaluation of the risk of restenosis after peripheral angioplasty: critical reflections]. PMID- 8350021 TI - [Silent myocardial ischemia]. AB - The frequency of silent myocardial ischemia (SMI) is 2 to 5% in an asymptomatic population, 25 to 30% after a myocardial infarction and 40% in stable angina. Although the prognosis of coronary insufficiency is related to the number of stenosed vessels and to left ventricular function, the presence of a silent ischemia constitutes an additive risk factor. The beneficial effect bypass surgery in terms of survival has been demonstrated in high risk patients (main coronary artery stenosis, three branch lesions with left ventricular insufficiency), while in the absence of symptoms those of medical treatment, and coronary angioplasty, have still to be demonstrated. PMID- 8350022 TI - Freeze-fracture studies on the cross-bridge angle distribution at various states and the thin filament stiffness in single skinned frog muscle fibers. AB - To give information about the changes of cross-bridge (myosin head) orientation during muscle contraction, mechanically skinned frog muscle fibers were rapidly frozen at various states, and the cross-bridges were observed on freeze-etch replicas. The number of cross-bridges per unit length of thick filament in relaxed state was less than one-third of that in contracting and rigor states. The interval between adjacent cross-bridges was maximum around 35 nm, a value close to the crossover repeat of actin helix. The cross-bridge angle distribution, as measured with a digital image processor, showed a peak around 90 degrees in all the states examined. The proportion of cross-bridges with angles around 90 degrees decreased either after stretch or after release of fibers in rigor state. The axial spacing of actin monomers in the thin filament was found to increase with increasing rigor force, to give the thin filament stiffness (times unit length) of about 1.8 x 10(4) pN. These results are discussed in connection with the mechanical properties of cross-bridges. PMID- 8350023 TI - Morphometric studies on the juxta-insular and tele-insular acinar cells of the pancreas in normal and streptozotocin-induced diabetic rats. AB - In the present study on the exocrine pancreas, stereological techniques were applied at the level of electron microscopy to confirm morphological differences between juxta-insular and tele-insular acinar cells of normal rats and to evaluate the effect of B cell secretion on these differences in streptozotocin diabetic rats. As no similar data have been previously published, we conducted a systematic sampling analysis with special reference to the acinar cell volume, the granule content and the nuclear size. In the normal rats, the juxta-insular acinar cell had an average volume of 918 microns3 and contained 420 zymogen granules which occupied 10.2% of the cell. In tele-insular acini, the average cell volume was estimated at 755 microns3 and the cell contained 231 zymogen granules which amounted to 6.8% of the cell. The juxta-insular acinar cell was 18% larger in size and contained 45% more zymogen granules, but no difference was observed in the size of zymogen granules. In addition, the numerical density of cell nuclei was slightly larger in the tele-insular acini in spite of the similarity in the volume density and diameter of the nuclei in the cells of the two areas. In the streptozotocin-induced diabetic rats, no differences were observed in the cell volume and the zymogen granule content between the juxta- and tele-insular acini. These data suggest that the morphological inhomogeneity in the pancreatic acini is caused by the influence of B cell secretion on the activity of the juxta-insular acini. PMID- 8350024 TI - Institutes of public health and medical schools: grasping defeat from the jaws of victory? PMID- 8350025 TI - Assessing the scientific quality of review articles. PMID- 8350026 TI - Coffee and tea consumption and the prevalence of coronary heart disease in men and women: results from the Scottish Heart Health Study. AB - STUDY OBJECTIVES: The aim was to determine if there was a relationship between coffee or tea consumption and the prevalence of coronary heart disease in Scotland. DESIGN: The relationship between self reported coffee and tea consumption and the prevalence of coronary heart disease (history, symptoms, or electrocardiographic evidence) was investigated using multiple logistic regression analysis in the Scottish Heart Health Study (SHHS), a cross sectional study. SETTING: Twenty two Scottish districts were surveyed for the SHHS between 1984 and 1986. SUBJECTS: A total of 10,359 men and women aged 40-59 years were studied. MEASUREMENTS AND MAIN RESULTS: Of the 9740 subjects who were assigned a category, 21.8% (2122) were classified as having indications of coronary heart disease. Men and women were combined in the odds ratio analysis because they showed almost identical patterns in the prevalence of coronary heart disease across the coffee and tea quarters (grouped according to consumption). Those who did not drink coffee had a significantly higher (p < 0.05) prevalence of coronary heart disease than the three groups for coffee drinkers. Adjustments for risk factors including cigarette smoking, total blood cholesterol, and diastolic blood pressure did not remove the significance of the odds ratios. There was a positive dose-response effect between tea consumption and coronary heart disease which was removed after adjustment for various risk factors. CONCLUSIONS: These findings do not support a positive relationship between coffee or tea consumption and coronary heart disease in this British study where most coffee consumed is instant coffee. PMID- 8350027 TI - Impact of social network on cardiovascular mortality in middle aged Danish men. AB - STUDY OBJECTIVE: To estimate quantitatively (the aetiological fraction) the impact of poor social network on premature death from cardiovascular disease in middle aged, white men. DESIGN: The causality of the relationship has already been discussed in a large review, and it is assumed to be well documented. The numerical estimation of the impact was based on a review of all published cohort studies on the relationship between social network and mortality in white, middle aged men. RESULTS: The studies reviewed are all of high epidemiological quality and present a consistent and stable dose-response pattern. The aetiological fraction was estimated to be 30%, with a plausible range of 20-40%. CONCLUSIONS: Social network was an important, independent, risk factor for cardiovascular disease in white, middle aged men. It had a strong impact on mortality, comparable to that of traditional risk factors. Social network should have a more central role in future epidemiological research into cardiovascular disease. The factors that result in a strong social network should be identified and strategies applicable in preventive work should be developed. PMID- 8350028 TI - Negative social events, stress, and health in Hong Kong. AB - STUDY OBJECTIVE: To investigate the association, if any, between negative social events and physical illness. DESIGN: Comparison of major social events and indices of disease. SETTING-Hong Kong, 1962 to 1985. SUBJECTS: Patients treated in hospital for attempted suicide, coronary heart disease, and diabetes mellitus. MEASUREMENTS AND MAIN RESULTS: Major events were selected from the annual Hong Kong Year Book, and grouped in one of 18 categories by a panel of 10 assessors. Weights were assigned to each category according the likely stress produced. Individual events were then scored and multiplied by the category weights to produce an overall stress score from which a total stress score for each year was derived. Annual stress scores were then compared with hospital attendance rates for the three medical conditions. CONCLUSIONS: The study has shown that: (1) the stress induced in the community by major negative social events in Hong Kong had been increasing; and (2) this stress is associated with attempted suicide but not with diabetes mellitus or coronary heart disease. PMID- 8350029 TI - Time trends in mortality in forestry and construction workers in Finland 1970-85 and impact of adjustment for socioeconomic variables. AB - STUDY OBJECTIVE: This study aimed firstly to describe the development of cause specific mortality in forestry workers, farmer/forestry workers, and skilled and semiskilled construction workers between 1970 and 1985 in Finland, and to compare this with mortality in the total working male population. The second aim was to evaluate how well the cause-specific mortality differences between the occupations could be explained by differences in socioeconomic status, marital status, or in the region of residence. DESIGN AND SETTING: This is a follow up study based on the 1970, 1975, and 1980 census records in Finland linked with all death certificates for 1971-75, 1976-80, and 1981-85 respectively. Log-linear regression analysis was used. SUBJECTS: All economically active men in Finland aged between 35 and 64 years in 1971-85 were studied. The number of person-years in the period totals about 10 million. MAIN RESULTS: Semiskilled construction workers had the highest mortality rate almost independent of the cause of death. The mortality of forestry workers was the second highest. Compared with the reference population, however, the differences were small with regard to neoplasms and cardiovascular diseases. With regard to other diseases, only the mortality of semiskilled workers was fairly high. Differences in mortality as a result of accidents were the highest. Both suicide and accidental death rates were high in semi-skilled construction workers and forestry workers. During the study total mortality fell by about 30% but mortality differences between groups did not decline. CONCLUSIONS: The high mortality of forestry and semiskilled construction workers is partly explained by socioeconomic factors such as marital status and housing conditions. These factors do not, however, explain the high suicide and accident mortality rates of forestry workers or semiskilled construction workers. More research is needed to explain these findings. PMID- 8350030 TI - High mortality in lower salaried Norwegian men: the healthy worker effect? AB - STUDY OBJECTIVE: This study aimed to examine whether the high mortality in lower salaried men in Norway was related to an inflow into this group of unskilled workers with high mortality. DESIGN: Individual information on occupation was derived from the 1970 and the 1980 censuses and linked to mortality data for the period 1980-5 by the official, individual identification numbers. PARTICIPANTS: The study population included Norwegian men aged 20-64 years in 1980. All men enumerated in the 1980 census (and who were registered in the 1970 census) within the two occupational groups, unskilled workers and lower salaried employees, were included. MEASUREMENTS AND MAIN RESULTS: The subjects were allocated to the two occupational groups according to the official Norwegian classification of socioeconomic status. Mortality was measured by standardised mortality ratios (SMR). The findings suggest that a fairly large number of unskilled workers with high mortality move into the lower salaried employee group. This transition produces a higher SMR in lower salaried employees and, simultaneously, an artificially but modestly lower SMR in unskilled workers. The difference in SMR between the two groups is thereby exaggerated by 44%. The difference among the elderly was smaller. CONCLUSION: Occupational mobility consistent with "the healthy worker effect" increases the SMR of lower salaried men and, at the same time, reduces slightly the SMR of unskilled workers. PMID- 8350031 TI - Trends in body mass index and prevalence of obesity in Swedish women 1980-89. AB - STUDY OBJECTIVE: To assess changes in the body mass index (BMI, weight (kg)/height2 (m2)) and in the prevalence of obesity in Swedish women during the 1980s. DESIGN: Data from two successive cross sectional surveys were used. SETTING: The whole of Sweden. SUBJECTS: A total of 7419 women from a 1980-81 survey (response rate 84.6%) and 6306 women from a 1988-89 survey (response rate 80.3%), aged 16-84 years, and forming a representative sample of Swedish women. MEASUREMENTS AND MAIN RESULTS: The results were based on self reported weight and height during interview. The mean BMI of the whole population, adjusted for age, education level, socioeconomic group, region, and nationality, increased by 0.17 kg/m2 (p = 0.0056) over the eight year period. The increase was particularly pronounced in the group aged 25-34 years (0.74 kg/m2; p < 0.0001, which corresponds to more than 2 kg for a woman 168 cm tall). The higher mean BMI was also reflected in the relative increase in the prevalence of obesity (BMI > 28.6 kg/m2) by 19% (odds ratio (OR) = 1.19; 95% confidence interval (CI): 1.04, 1.37) and of the combination of overweight and obesity (BMI > 23.8 kg/m2) by 12% (OR = 1.12; 95% CI 1.03, 1.23) in the whole female population. CONCLUSIONS: During the 1980s the mean BMI and the prevalence of overweight and obesity in adult Swedish women increased. An influence of the sociocultural environment on the body weight in women was stronger than that in men. PMID- 8350033 TI - Evidence for longevity differences between left handed and right handed men: an archival study of cricketers. AB - STUDY OBJECTIVE: The aim was to examine the relationship between handedness and longevity. DESIGN: This was an archival (retrospective) survey of a cohort of adult men who had played 'first-class cricket'. SETTING: The United Kingdom PARTICIPANTS: The subjects consisted of all of the deceased players included in an encyclopedia of 'first-class cricket' whose bowling hand had been recorded (n = 3165). The study also considered a further 2314 players, born before 1951 but still alive at the time the book was published (1984). MEASUREMENTS AND MAIN RESULTS: Using the bowling hand as an indicator of handedness it was possible to compare the lifespans of 2580 right handed men and 585 left handed men. The average life spans of the two groups differed by 25 months (right = 65.62, left = 63.52), a highly significant difference (p = 0.006). An examination of cause of death (where noted) strongly indicated that the left handed men were more likely to die prematurely in accidents or in warfare. As a consequence, when these unnatural deaths were removed from the sample the longevity difference between the right handers and left handers was considerably reduced. There was no evidence that these results related to any longitudinal change in the proportion of right handers to left handers across the time course of the sample. CONCLUSION: The study found clear evidence that left handedness was associated with a decrease in longevity among a cohort of adult, athletic men. A major factor responsible for this result seemed to be a differential likelihood of accidental death or death during warfare. PMID- 8350032 TI - Magnitude and causes of mortality differences between married and unmarried men. AB - STUDY OBJECTIVE: To determine the effect of marital status on mortality for men. In particular, to examine whether subgroups of unmarried men (widowed, single, and divorced/separated men) have a similar mortality to married men. DESIGN: Cohort study. SETTING: Whitehall civil service, London, between 1967 and 1969. PARTICIPANTS: A total of 18,403 men aged 40-64 years with 18 years' follow up. MEASUREMENTS AND MAIN RESULTS: Cause-specific mortality rates and risk factors at baseline were determined. Overall mortality was greater for all groups of unmarried men. Patterns of mortality were different in the subgroups of unmarried men. Widowed men had a significantly greater risk of dying from ischaemic heart disease (relative risk (RR) 1.46, 95% confidence interval (CI) 1.08, 1.97) which persisted after exclusion of deaths that occurred in the first two years. Divorced men had greater cancer mortality (RR 1.49; 95% CI 1.06, 2.10) that could not be explained simply by their greater consumption of cigarettes. The initial increased mortality for single men was no longer evident after adjustment for other risk factors, suggesting that single status in itself may not increase the risk. The risk for single men may have been underestimated, however, by over adjustment for possible intermediary factors. CONCLUSIONS: Previous studies, which have examined total mortality only or have grouped all unmarried men, have masked interesting differences in the cause of death between subgroups of unmarried men. The extent to which the findings are explicable by psychosocial factors or the role of other environmental factors, which may also differ in relation to marital status, is unclear. Future work should not assume that all unmarried men have similar mortality risks and must examine the life course of each subgroup to advance our understanding of the possible causal role of marital status in disease aetiology. PMID- 8350034 TI - Paralytic poliomyelitis in children under 6 years in Pondicherry: a community survey. AB - STUDY OBJECTIVES: To assess the amount of poliomyelitis and its epidemiological features including risk factors. DESIGN: This was a retrospective study of cases of paralytic poliomyelitis among children 0-6 years of age. SETTING: Pondicherry, India, 1983-89. SUBJECTS: A total of 47,960 children aged less than 6 years. MEASUREMENTS AND MAIN RESULTS: In 1989, 469 field workers undertook a door to door survey of children 0-6 years old to identify those with limb paralysis. This was followed by clinical examination to establish the cause, supplemented by case notes held by the Child Development Services. Altogether 203 cases of limb paralysis were identified, 188 of which were judged a result of paralytic poliomyelitis. The prevalence of poliomyelitis in 1989 was 3.9/1000 among children below 6 years of age. There was a male preponderance with a male:female ratio of 1.4:1. The prevalence was least in infants (1/1000) and highest in children aged 2 to 3 years (6.4/1000). The age at onset was less than 12 months in 42% of cases and less than 3 years in 98%. The median age at onset was 13.4 months. Time series analysis showed a high occurrence of cases from May to September between 1983 and 1989. The legs were affected in 97%. About 41% of children had received three doses of oral polio vaccine. There was a history of intramuscular injection, possibly provoking a paralytic attack, in 54% of cases. CONCLUSION: This retrospective community study involving the staff of the Integrated Child Development Services provided valid data about poliomyelitis with little additional cost and minimum training. Because the study covered a whole population of children under 6 years, rather than a sample, the data will help in monitoring and surveillance of poliomyelitis and also in planning strategies for effective control. PMID- 8350035 TI - Economics of a reduction in smoking: case study from Heartbeat Wales. AB - STUDY OBJECTIVE: This study aims to apply economic principles and techniques in evaluating a health promotion programme. DESIGN: This study is an economic appraisal of the Heartbeat Wales no smoking intervention programme. The costs incurred over the four year period 1985-89 have been identified and estimates have been made of the likely future impact of the reduced smoking prevalence within Wales in terms of reduced morbidity and displaced mortality in three disease groups--coronary heart disease, lung cancer, and chronic bronchitis. SETTING: Wales, UK. RESULTS: The net present value of benefits is considerably greater than costs in terms of both the NHS and the economy as a whole in Wales. In addition, the net costs per life year saved shows that the programme generates additional working life years at relatively low cost. Because not all the benefits can be fully attributed to the programme 'impact rates' ranging from 100 to 10% have been applied to the level of benefits. The evidence suggests that even if only 10% of the benefits could be attributed to the programme there is still a positive net present value of benefits. The relative efficiency of this programme has not been considered here. CONCLUSION: Large scale benefits to the NHS and the economy as a whole can be derived from reductions in smoking. PMID- 8350036 TI - Factors affecting response to an invitation to attend for a health check. AB - OBJECTIVE: To describe the characteristics of general practice patients who fail to respond to an invitation to attend for a health check, in relation to demographic variables, risk factor status, health status, and attitudes to behaviour modification. DESIGN: Postal questionnaire before invitation to attend a health check and subsequent record of attendance. SETTING: Five urban general practices in Bedfordshire, UK. SUBJECTS: A total of 2678 patients aged 35-64 years were invited for a health check in 1989-90. RESULTS: The number of patients who did not attend was low overall but was higher among men than women (21 v 15%, p < 0.001), and in unmarried than married patients (24 v 16%, p < 0.001). Failure to attend was also higher among people in manual than in non-manual occupations (21 v 15%, p < 0.001), in people living in rented accommodation than in homeowners (29 v 16%, p < 0.001), and in those without access to a car than in car users (27 v 16%, p < 0.001). There was no difference in non-attendance rate according to age at completion of full time education. After adjustment for age, sex, marital state, and social class, the odds ratio for non-attendance was 1.74 (95% confidence interval (CI) 1.41, 2.14) for smokers; 1.07 (95% CI 0.76, 1.51) for heavy drinkers; 1.91 (95% CI 1.41, 2.58) for those with a less healthy diet; and 1.50 (95% CI 1.09, 2.07) for those who were obese. Patients who had visited their general practice more frequently and those who indicated a willingness to change their behaviour were significantly more likely to attend the health check. CONCLUSIONS: Health check attendance was lowest among patients who rarely attended the surgery and those who reported higher risk behaviour. Attendance was not, however, confined to the 'worried well'. Equal numbers of those with and without chest pain attended, as did at least three quarters of those in each risk group. This high rate of attendance reflects the time and effort invested in systematic recruitment. The development of a robust recruiting strategy is essential if substantial numbers, and particularly those at highest risk, are to be reached. PMID- 8350037 TI - Diagnostic delay, clinical stage, and social class: a hospital based study. AB - STUDY OBJECTIVE: To measure delay in admission to a large hospital and to study the role of social class and other potential determinants of delay. DESIGN: Interview of a 10% sample of newly diagnosed patients admitted to medical or surgical wards, and all those admitted for external hernia or colon cancer between June 1989 and May 1990. SETTING: The largest hospital in an Italian region of five million inhabitants. SUBJECTS: The study population consisted of 330 patients with a range of different medical and surgical conditions, 83 patients with external hernias, and 97 patients with colon cancers. MEASUREMENTS AND MAIN RESULTS: After patient interview and discharge from hospital, the clinical record was consulted for information on the length of stay and the diagnosis, and in particular for the staging of hernia or colon cancer (according to the protocol of the Jefferson Medical College). Multiple logistic regression was used to estimate odds ratios and 95% confidence intervals. There was an association between advanced disease at hospital admission and the patient's educational level. In each of the three groups of patients, those with the highest educational level had a 30% or lower probability of being admitted to hospital with advanced disease compared with those with the lowest education level (after allowance for sex, age, area of residence, and marital status). CONCLUSION: Lower social class was associated with a more advanced clinical stage of hernia or colon cancer, and with a higher probability of urgent admission to the hospital for a newly diagnosed disease. Delay in seeking care, did not however, seem to explain the social class differentials for disease stage. PMID- 8350038 TI - Patterns of hospital care for patients with HIV infection and AIDS. AB - OBJECTIVE: The aims were to describe the use of inpatient resources by patients with HIV infection and patients with AIDS; to examine trends in service use over time; and to provide data for planners concerned with service provision for HIV infection. SETTING: An inner London health district reporting 9% of AIDS cases nationally. DESIGN: Data on survival times and inpatient and day care use of resources were derived from existing patient records or collected prospectively between 1983 (when the first case of AIDS was diagnosed in the district) and 31 March 1990. SUBJECTS: A total of 488 HIV positive patients of whom 396 had been diagnosed as having AIDS were studied. MEASUREMENTS AND MAIN RESULTS: Inpatient days consumed per annum; trends in the number of bed days per person year with AIDS; the lifetime inpatient use per AIDS patient; and the influence of survival on service use estimates were determined. Altogether 16.4% of a total 17,785 hospital inpatient days were attributable to HIV positive patients who did not fulfil the criteria for AIDS. For patients with AIDS, there was an initial increase in the intensity of inpatient use in 1987 when a dedicated HIV ward was opened. After 1988, however, inpatient use fell to 30.8 bed days per person year with AIDS. Patients diagnosed after April 1987 had noticeably longer survival times than those diagnosed earlier (a median of 17-18 months compared with a median of 10-11 months). From 214 lifetime service use records, it was estimated that patients with short survival (less than six months) would consume 36 days of inpatient care, while those expected to survive longer would consume approximately twice that number of days, irrespective of how much longer they survived. CONCLUSIONS: The data indicate less intensive use of inpatient care by AIDS patients over time, and hence the apparent ability to manage an increasing AIDS patient workload without a comparable increase in occupied bed days. Increases in the size of that workload and changes in the survival profile of patients, together with a relatively constant rate of service demand by longer survivors, however, will continue to place increasing strains on finite inpatient resources. Further research is needed to establish the extent to which the greater use of outpatient and community services can offset this. PMID- 8350039 TI - Do inaccuracies in small area deprivation analyses matter? AB - OBJECTIVE: To assess the accuracy of computerised matching of postcode to enumeration district (ED) and to determine whether any mismatching reduces the validity of methods to distinguish socioeconomic differences in "small area" deprivation studies. DESIGN: Computerised and manual matching of postcodes to EDs were compared and the census based Townsend deprivation score was compared with socioeconomic data on individual families. SETTING: County of Northumberland, England, 1989. SUBJECTS: Random sample of 301 families with a child aged less than 15 months. MAIN RESULTS: With computerised matching only 47% of postcodes were matched to the correct ED. Eighty per cent of the deprivation scores of the computer matched EDs, however, approximated (+/- 2) to the deprivation score of the actual ED. When EDs were divided into quintiles according to the deprivation score, accurate manual matching showed that 75% of families in the most deprived EDs were classed as deprived compared with 4% in the most affluent EDs. With the inaccuracies introduced by computer matching of postcodes, the corresponding figures were 56% and 12% respectively. CONCLUSIONS: Computerised matching of postcodes to EDs is highly inaccurate, but this has little effect on the allocation of deprivation scores. The socioeconomic inequalities shown by the deprivation score are blunted, but not eradicated, by this mismatching. PMID- 8350040 TI - Multi method approach to the assessment of data quality in the Finnish Medical Birth Registry. AB - OBJECTIVE: To assess comprehensively the validity of the data in the Finnish Medical Birth Registry (MBR) by the combined use of several controls and internal analysis of the data. DESIGN: The MBR data were individually linked to a medical record sample (n = 775) and to all perinatal death certificates in 1987. The data were also compared with annual hospital statistics. The distributions of birth weights and gestational ages were examined. SUBJECTS: All stillborn and liveborn babies registered in the MBR in 1987 (n = 59,370). SETTING: The nationwide MBR data were compared with medical records from one third of the Finnish hospitals, with statistics for all hospitals, and with nationwide cause of death registry data. MEASUREMENTS AND MAIN RESULTS: With regard to most variables, the data quality was good or satisfactory (agreement with medical records 95% or more). Allowing for minor deviations in variables with continuous scales improved the agreement rates further. Explanations could be deduced for items with poor agreement values. For most variables, the amount of missing data was less than 1%. With the exception of caesarean sections, medical procedures were registered in only 30 to 72% of the cases, and the proportion varied strongly between the hospitals. Common diagnoses (32 to 86%) and primary causes of death (59 to 78%) were also poorly recorded. CONCLUSIONS: Combined use of several control materials and internal analyses was successful in investigating the whole data content. The data in the MBR were generally valid but diagnoses and most data on medical procedures were not of sufficiently good quality. PMID- 8350041 TI - Improving mortality data in South Africa: review of next of kin statements to determine cause of death in police certification. AB - STUDY OBJECTIVE: The study aimed to improve mortality data by finding ways of reducing the large number of deaths certified as being from "ill-defined" causes (ICD 780-798) in South Africa. This problem is attributable to the absence of cause of death information in many cases where the police issue the death certificate. DESIGN AND SETTING: A total of 600 consecutive death certification records at the Salt River State Mortuary, Cape Town were reviewed. MEASUREMENTS AND MAIN RESULTS: Altogether 347 (58%) deaths were from unnatural causes, 111 (18%) were certified by a doctor, 83 (14%) were certified as being the result of natural causes after a necropsy, and 59 (10%) were certified by the police as being from natural causes. Analysis of sworn statements obtained from the next of kin of all those certified dead by the police rather than a doctor provided a clear cause of death in 72.9%, and a history of recent contact with health services (less than one week previously) in 47.5%. All infants certified dead by the police had a history consistent with diarrhoeal disease. CONCLUSIONS: The method of death certification may be an indicator of access to health care and reviewing sworn statements to determine the cause of death should improve the quality of mortality data in the developing world. PMID- 8350042 TI - High frequency of normal DJH joints in B cell progenitors in severe combined immunodeficiency mice. AB - The severe combined immunodeficiency (scid) mouse has a defective V(D)J recombinase activity that results in arrested lymphoid development at the pro-B cell stage in the B lineage. The defect is not absolute and scid mice do attempt gene rearrangement. Indeed, approximately 15% of all scid mice develop detectable levels of oligoclonal serum immunoglobulin and T cell activity. To gain more insight into the scid defect and its effect on V(D)J rearrangement, we analyzed DJH recombination in scid bone marrow. We determined that DJH structures are present in scid bone marrow and occur at a frequency only 10-100 times less than C.B-17+/+. The scid DJH repertoire is limited and resembles fetal liver DJH junctions, with few N insertions and predominant usage of reading frame 1. Moreover, 70% of the DJH structures were potentially productive, indicating that normal V(D)J recombinants should be arising continually. PMID- 8350043 TI - Hck tyrosine kinase activity modulates tumor necrosis factor production by murine macrophages. AB - The hematopoietic cell kinase (hck) is a member of the src family of tyrosine kinases, and is primarily expressed in myeloid cells. Hck expression increases with terminal differentiation in both monocyte/macrophages and granulocytes and is further augmented during macrophage activation. Recent evidence has implicated src-related tyrosine kinases in critical signaling pathways in other hematopoietic lineages. Herein we demonstrate that manipulation of the level of hck expression in the murine macrophage cell line BAC1.2F5 alters the responsiveness of these cells to activation by bacterial lipopolysaccharide (LPS) but does not affect survival or proliferation. Overexpression of an activated mutant of hck in BAC1.2F5 cells augments tumor necrosis factor (TNF) production in response to LPS, whereas inhibition of endogenous hck expression, by antisense oligonucleotides, interferes with LPS-mediated TNF synthesis. Together, these observations suggest that hck is an important component of the signal transduction pathways in activated macrophages. PMID- 8350044 TI - The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell. AB - One of the distinguishing features of multiple myeloma (MM) is the proliferation of a clonal plasma cell population in the bone marrow (BM). It is of particular interest that the tumor plasma cells appear to be restricted to the microenvironment of the BM and are rarely detected in the peripheral system, yet the disease is found widely disseminated throughout the axial skeleton. Furthermore, isolation of MM tumor cell lines has proven to be quite problematic due to their slow growth rate. These observations have instigated the search for earlier cells in the B cell lineage that are clonally related to the plasma cell tumor and that may represent the growth fraction of the tumor. We used allele specific oligonucleotides (ASO) derived from the third complementarity determining region of the rearranged tumor immunoglobulin heavy chain gene to detect isotypes clonally related to the plasma cell tumor. By reverse transcribing RNA from the BM with a panel of CH primers (mu, delta, alpha, and gamma), followed by ASO-polymerase chain reaction amplification, we demonstrate the existence of preswitch isotype species that are clonally related to the myeloma tumor. Furthermore, we show that separation of the BM cells into CD45+ and CD38+ cell populations results in a lineage-specific expression of the clonally related RNA molecules, with the C mu and C delta in the CD45+, and C gamma in the CD38+ population. Interestingly, clonally related C alpha transcripts are also derived from the CD45+ fraction. These results confirm the presence of B cell populations clonally related to the plasma cell tumor and are consistent with models that propose the existence of myeloma precursors. PMID- 8350045 TI - Human natural killer (NK) alloreactivity and its association with the major histocompatibility complex: ancestral haplotypes encode particular NK-defined haplotypes. AB - As ancestral haplotypes of the major histocompatibility complex (MHC) appear to define identical MHC haplotypes in unrelated individuals, unrelated individuals sharing the same ancestral haplotype should also share the same NK-defined allospecificities that have recently been shown to map to the human MHC. To test this prediction, multiple cell lines from unrelated individuals sharing the same ancestral haplotypes were tested for the NK-defined allospecificities. It was found that cells sharing the same ancestral haplotypes do have the same NK defined specificities. Furthermore, the NK-defined phenotype of cells that possess two different ancestral haplotypes can be predicted from the NK-defined phenotypes of unrelated cells that are homozygous for the ancestral haplotypes concerned. Although the group 1 and 2 NK-defined allospecificities can be explained to some extent by HLA-C alleles, evidence is presented that additional genes may modify the phenotype conferred by HLA-C. PMID- 8350046 TI - IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo. AB - IP-10 is a member of the -C-X-C-chemokine superfamily of proinflammatory cytokines whose secretion is induced by interferon gamma (IFN-gamma) and lipopolysaccharide (LPS). To date no function has been described for IP-10. We have genetically engineered tumor cells to secrete high levels of murine IP-10 and demonstrate that while IP-10 has no effect on the growth of these tumor cells in culture, it elicits a powerful host-mediated antitumor effect in vivo. The IP 10 antitumor response is T lymphocyte dependent, non-cell autonomous, and appears to be mediated by the recruitment of an inflammatory infiltrate composed of lymphocytes, neutrophils, and monocytes. These results document an important biologic property of IP-10 and raise the possibility that some of the T cell directed effects of IFN-gamma and LPS may be mediated by this chemokine. PMID- 8350047 TI - Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia. AB - D factor, also known as leukemia inhibitory factor, is a pleiotropic cytokine whose role during acute injury and inflammation is not known. Intraperitoneal administration of Escherichia coli endotoxin induced D factor gene expression in mice, and passive immunization against D factor protected them from the lethal effects of endotoxin and blocked endotoxin-induced increases in serum levels of interleukin 1 and 6. Peak levels of tumor necrosis factor and interferon gamma were not affected. These results indicate that D factor is an essential early mediator of the inflammatory cytokine response and therefore may be important in the pathogenesis of the many inflammatory conditions, such as sepsis, arthritis, allograft rejection, and cancer immunotherapy. PMID- 8350048 TI - Evidence for a bone marrow B cell transcribing malignant plasma cell VDJ joined to C mu sequence in immunoglobulin (IgG)- and IgA-secreting multiple myelomas. AB - Multiple myeloma is a B cell malignancy characterized by the expansion of plasma cells producing monoclonal immunoglobulins (Ig). It has been regarded as a tumor arising at the B, pre-B lymphocyte, or even stem cell level. Precursor cells are presumed to proliferate and differentiate giving rise to the plasma cell clonal expansion. Antigenic features and specific Ig gene rearrangement shared by B lymphocytes and myeloma cells have supported this hypothesis. However, the existence of such a precursor is based upon indirect evidence and is still an open question. During differentiation, B cells rearrange variable (V) regions of Ig heavy chain genes, providing a specific marker of clonality. Using an anchor polymerase chain reaction assay, these rearranged regions from five patients with multiple myeloma were cloned and sequenced. The switch of the Ig constant (C) region was used to define the B cell differentiation stage: V regions are linked to C mu genes in pre-B and B lymphocytes (pre-switch B cells), but to C gamma or C alpha in post-switch B lymphocytes and plasma cells (post-switch B cells). Analysis of bone marrow cells at diagnosis revealed the presence of pre-switch B cells bearing plasma cell V regions still joined to the C mu gene. These cells were not identified in peripheral blood, where tumor post-switch B cells were detected. These pre-switch B cells may be regarded as potential myeloma cell precursors. PMID- 8350050 TI - Interleukin 7 is produced by murine and human keratinocytes. AB - Interleukin 7 (IL-7) was originally identified as a growth factor for B cell progenitors, and subsequently has been shown to exert proliferative effects on T cell progenitors and mature peripheral T cells as well. Constitutive IL-7 mRNA expression so far had been demonstrated in bone marrow stromal cell lines, thymus, spleen, and among nonlymphoid tissues in liver and kidney. Here we show that both murine and human keratinocytes express IL-7 mRNA and release IL-7 protein in biologically relevant amounts. The physiological or pathological relevance of keratinocyte-derived IL-7 is presently unknown. Our finding that keratinocytes can produce IL-7 in concert with reports that IL-7 is a growth factor for in vivo primed antigen-specific T cells, as well as for T lymphoma cells suggests, however, that keratinocyte-derived IL-7 is important in the pathogenesis of inflammatory skin diseases and cutaneous T cell lymphoma. PMID- 8350049 TI - Selective long-term elimination of natural killer cells in vivo by an anti interleukin 2 receptor beta chain monoclonal antibody in mice. AB - The interleukin 2 receptor beta chain (IL-2R beta) is preferentially expressed in natural killer (NK) cells, but is not detected in a majority of resting T and B cells. We recently established a novel monoclonal antibody (mAb) to murine IL-2R beta and examined in vivo the effect of the mAb in mice. We found that intraperitoneal injection of the anti-IL-2R beta mAb into adult mice resulted in a selective in vivo elimination of splenic NK function in various mouse strains. The reduction of NK cell function is associated with complete disappearance of NK1.1+ cells in C57BL/6 mice. Other lymphocyte subsets in the thymus and spleen were uncompromised. T cell function was not affected by the mAb treatment as judged by allogeneic cytotoxic T cell induction. The single injection of anti-IL 2R beta mAb caused a long-term elimination of splenic NK cells, lasting for at least 5 wk. We also found that NK and/or NK precursor cells become susceptible to the mAb treatment only after birth, suggesting that functional maturation of NK cells in terms of IL-2R beta expression is a later event in the course of NK cell development. The use of the anti-IL-2R beta mAb will be useful in defining the physiological role of NK cells in host defense as well as dissecting their developmental pathway in vivo. PMID- 8350051 TI - Human interferon-inducible protein 10: expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors. AB - Human interferon-inducible protein 10 (IP-10), a member of the family of the small secreted proteins called intercrine cytokines or chemokines, is secreted by interferon gamma-stimulated T cells, monocytes, endothelial cells, and keratinocytes. We have begun to explore the biological properties of IP-10 by cloning and overexpression in baculovirus and in bacterial protein expression systems. A 9.9-kD protein was secreted by infected insect cells, which on sodium dodecyl sulfate-polyacrilamide gel electrophoresis comigrated with keratinocyte IP-10 and with f(22-98), a bacterial recombinant fragment lacking the signal sequence but containing all other residues of IP-10. All three reacted with antibodies recognizing residues 10-98 (alpha IP-10) and 77-98 of IP-10 (alpha 22), demonstrating that it is secreted by keratinocytes and insect cells after removal of the signal sequence but without proteolysis of the COOH-terminal end. Purified rIP-10 suppresses in vitro colony formation by early human bone marrow progenitor cells which need r-steel factor (rSLF) and rGM-CSF or rSLF and r erythropoeitin (rEPO). The inhibition is dose dependent, is complete at concentrations > or = 50 ng/ml, is prevented by preincubation of rIP-10 with alpha IP-10, but not by alpha 22, and is seen with highly purified CD34+ cells, suggesting direct effect of rIP-10 on the progenitors. Combination of rIP-10 and other chemokines at inactive concentrations inhibited colony formation in a synergistic manner. rIP-10 did not affect colony formation in the absence of any growth factors or in the presence of rEPO or rGM-CSF but in absence of rSLF. The effects of IP-10 may be relevant to normal marrow function and might be harnessed to protect human hematopoietic progenitors from the cytotoxic effects of chemotherapy. PMID- 8350052 TI - Antibodies against major histocompatibility complex class II antigens directly inhibit the growth of T cells infected with Theileria parva without affecting their state of activation. AB - We have analyzed the effect of antibodies (Abs) directed against major histocompatibility complex (MHC) class II Abs on the proliferation of Theileria parva-infected (Tpi) T cells. Anti-MHC class II Abs exert a direct effect on Tpi T cells causing an acute block in their proliferation. The inhibition does not involve apoptosis and is also entirely reversible. The rapid arrest of DNA synthesis caused by anti-MHC class II Abs is not due to interference with the state of activation of the T cells since the transcriptional activator NF-kappa B remains activated in arrested cells. In addition, interleukin 2 (IL-2), IL-2R, and c-myc gene expression are also unaffected. By analyzing the cell-cycle phase distribution of inhibited cells, it could be shown that cells in all phases of the cell cycle are inhibited. The signal transduction pathway that results in inhibition was shown to be independent of protein kinase C and extracellular Ca2+. Tyrosine kinase inhibitors, however, partly reduced the level of inhibition and, conversely, phosphatase inhibitors enhanced it. The possible relevance of this phenomenon in other systems is discussed. PMID- 8350053 TI - Human keratinocytes release the endogenous beta-galactoside-binding soluble lectin immunoglobulin E (IgE-binding protein) which binds to Langerhans cells where it modulates their binding capacity for IgE glycoforms. AB - A better understanding of the pathophysiological role of Langerhans cells (LC) in atopic diseases is dictated by the characterization of the structures involved in immunoglobulin (IgE)-binding on their cell surface. We previously reported that human LC express the high affinity receptor for IgE (Fc epsilon RI), as well as the low affinity receptor for IgE (Fc epsilon RII/CD23). In the present study, we document the presence of a third IgE-binding structure on human LC, the IgE binding protein (epsilon BP), an endogenous soluble beta-galactoside binding lectin. Immunohistochemical studies performed on normal human skin revealed an anti-epsilon BP reactivity in the cytoplasm of keratinocytes and in that of acinous cells of eccrine sweat glands. epsilon BP was also found on the cell surface of LC, as shown by anti-epsilon BP/anti-CD1a double labeling and flow cytometric analysis. Anti-epsilon BP binding to the surface of LC was completely abolished by preincubation with lactose and restored by addition of recombinant human epsilon BP, indicating that epsilon BP binds to LC surface by virtue of its lectin property. Immunoblot analysis of anti-epsilon BP-reactive material in keratinocytes and purified LC disclosed a protein with an apparent molecular weight of 33,000 consistent with epsilon BP. Interestingly, mRNA transcripts for epsilon BP were detected only in keratinocytes but not in purified LC isolated from normal skin. epsilon BP was found to be released in culture supernatants of keratinocytes. Incubation of LC with these supernatants resulted in epsilon BP binding to LC surface via protein-carbohydrate interaction. Most importantly, we could show that binding of human myeloma IgE to LC was inhibited by epsilon BP. In contrast, neuraminidase-treated human myeloma IgE binds to LC only in the presence of epsilon BP. In situ binding studies revealed that keratinocytes, although containing epsilon BP intracytoplasmatically, failed to exhibit any IgE binding properties. Collectively, our results suggest that human keratinocytes produce the beta-galactoside-binding lectin epsilon BP, which subsequently binds to the surface of LC where it is functional in modulating their binding capacity for IgE glycoforms. PMID- 8350055 TI - Somatic variation precedes extensive diversification of germline sequences and combinatorial joining in the evolution of immunoglobulin heavy chain diversity. AB - In Heterodontus, a phylogenetically primitive shark species, the variable (VH), diversity (DH), joining (JH) segments, and constant (CH) exons are organized in individual approximately 18-20-kb "clusters." A single large VH family with > 90% nucleic acid homology and a monotypic second gene family are identified by extensive screening of a genomic DNA library. Little variation in the nucleotide sequences of DH segments from different germline gene clusters is evident, suggesting that the early role for DH was in promoting junctional diversity rather than contributing unique coding specificities. A gene-specific oligodeoxynucleotide screening method was used to relate specific transcription products (cDNAs) to individual gene clusters and showed that gene rearrangements are intra- rather than intercluster. This provides further evidence for restricted diversity in the immunoglobulin heavy chain of Heterodontus, from which it is inferred that combinatorial diversity is a more recently acquired means for generating diversity. The observed differences between cDNA sequences selected and the sequences of segmental elements derived from conventional genomic libraries as well as from VH segment-specific libraries generated by direct PCR amplification of genomic DNA indicate that the VH repertoire is diversified by both junctional diversity and somatic mutation. Taken together, these findings suggest a heretofore unrecognized contribution of somatic variation that preceded both extensive diversification of the germline repertoire and the combinatorial joining process in the evolution of humoral immunity. PMID- 8350054 TI - I-E+ nonobese diabetic mice develop insulitis and diabetes. AB - The development of type I diabetes in the nonobese diabetic (NOD) mouse is under the control of multiple genes, one or more of which is linked to the major histocompatibility complex (MHC). The MHC class II region has been implicated in disease development, with expression of an I-E transgene in NOD mice shown to provide protection from insulitis and diabetes. To examine the effect of expressing an I-E+ or I-E- non-NOD MHC on the NOD background, three I-E+ and three I-E- NOD MHC congenic strains (NOD.H-2i5, NOD.H-2k, and NOD.H-2h2, and NOD.H-2h4, NOD.H-2i7, and NOD.H-2b, respectively) were developed. Of these strains, both I-E+ NOD.H-2h2 and I-E- NOD.H-2h4 mice developed insulitis, but not diabetes. The remaining four congenic strains were free of insulitis and diabetes. These results indicate that in the absence of the NOD MHC, diabetes fails to develop. Each NOD MHC congenic strain was crossed with the NOD strain to produce I-E+ and I-E- F1 mice; these mice thus expressed one dose of the NOD MHC and one dose of a non-NOD MHC on the NOD background. While a single dose of a non NOD MHC provided a large degree of disease protection to all of the F1 strains, a proportion of I-E+ and I-E- F1 mice aged 5-12 mo developed insulitis and cyclophosphamide-induced diabetes. When I-E+ F1 mice were aged 9-17 mo, spontaneous diabetes developed as well. These data are the first to demonstrate that I-E+ NOD mice develop diabetes, indicating that expression of I-E in NOD mice is not in itself sufficient to prevent insulitis or diabetes. In fact, I-E- F1 strains were no more protected from diabetes than I-E+ F1 strains, suggesting that other non-NOD MHC-linked genes are important in protection from disease. Finally, transfer of NOD bone marrow into irradiated I-E+ F1 recipients resulted in high incidences of diabetes, indicating that expression of non-NOD MHC products in the thymus, in the absence of expression in bone marrow-derived cells, is not sufficient to provide protection from diabetes. PMID- 8350056 TI - Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome. AB - Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire. PMID- 8350057 TI - A first or dominant immunization. I. Suppression of simultaneous cytolytic T cell responses to unrelated alloantigens. AB - A first or dominant immunization with one antigen markedly inhibited specific cytolytic T lymphocyte (CTL) responses to a second unrelated alloantigen without suppressing antibody responses to other antigens. Suppression was induced rapidly, became systemic, and could be transferred passively with only serum. Suppression did not result from elimination of cells capable of responding to the second antigen. The mechanisms responsible for this "priority of the first response" may be the same that help protect the fetus during pregnancy, promote renal allograft survival after multiple blood transfusions, and prevent effective CTL-mediated immunity to variants of tumor cells or infectious agents that arise during tumor progression or chronic infections. PMID- 8350058 TI - A first or dominant immunization. II. Induced immunoglobulin carries transforming growth factor beta and suppresses cytolytic T cell responses to unrelated alloantigens. AB - Fresh sera from mice immunized by bearing an immunogenic tumor or by repeated injections of allogeneic spleen cells or xenogeneic erythrocytes powerfully suppress cytolytic T cell responses in one-way mixed lymphocyte cultures. Suppression is not antigen specific, though is mediated by immunoglobulin (Ig)G specific for the immunizing antigen. Suppression caused by IgG mimics that caused by active transforming growth factor beta (TGF-beta). IgG associates with or carries latent TGF-beta; however, suppression caused by the complex of IgG-TGF beta requires macrophages (M phi), whereas active TGF-beta alone does not. Also, IgG dissociated from TGF-beta does not cause suppression, suggesting that M phi may take up Ig-TGF-beta, process the complex, and deliver active TGF-beta to lymphocytes. Indeed, suppression by immune serum was prevented by antibody to Fc receptors, by saturating Fc receptors with heterologous IgGs, and by antibodies against TGF-beta. The overall findings reveal a previously unrecognized regulatory circuit whereby IgG produced in response to one antigen nonspecifically downregulates cytolytic T lymphocyte responses to unrelated antigens. The findings introduce the intriguing possibility that TGF-beta delivered by IgG and processed by M phi may mediate important biological effects in processes such as wound healing, tumor growth, and some autoimmune diseases. PMID- 8350059 TI - Human keratinocyte growth factor effects in a porcine model of epidermal wound healing. AB - Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family (hence the alternative designation FGF-7). It is produced by stromal cells, but acts as a mitogen for epithelial cells. We examined the effects of topically applied KGF on healing of wounds in a porcine model. In partial thickness wounds, KGF stimulated the rate of reepithelialization (p < 0.0002), associated with a thickening of the epidermis (p < 0.0001). Epidermis from KGF treated full-thickness wound sites was significantly thicker (0.31 +/- 0.22 mm) compared with mirror image control sites (0.18 +/- 0.12 mm) (p < 0.0001). Moreover, the majority (77%) of KGF-treated wounds exhibited epidermis with a deep rete ridge pattern as compared with control sites. These effects were observed as early as 14 d and persisted for at least 4 wk. KGF treatment also increased the number of serrated basal cells associated with increased deposition of collagen fibers in the superficial dermis adjacent to the acanthotic epidermis. Electron microscopy revealed better developed hemidesmosomes associated with thicker bundles of tonofilaments in the serrated cells. The pattern of epidermal thickening observed in KGF-treated wounds resembled psoriasis. Psoriasis is a disease associated with epidermal thickening, parakeratosis as well as hyperproliferation that extends beyond the basal layer. In striking contrast to psoriasis, KGF-treated wounds exhibited normal orthokeratotic maturation, and proliferation was localized to the basal cells. Our present findings have significant implications concerning the role of KGF as a paracrine modulator of epidermal proliferation and differentiation. PMID- 8350060 TI - Positive selection of V beta 8+ CD4-8- thymocytes by class I molecules expressed by hematopoietic cells. AB - A small subset of T cells of mature phenotype express the alpha/beta T cell receptor, but not CD4 and CD8 coreceptors (alpha/beta double-negative [DN] cells). The repertoire of V beta usage of alpha/beta DN cells is strongly biased towards V beta 8 expression, suggesting that the formation of the population is subject to selection. We now report that deficiency of class I expression leads to a strongly depressed frequency of V beta 8+ DN cells, but has little effect on V beta 8- DN cells. Studies of hematopoietic chimeras between class I+ and class I- mice demonstrated that expression of class I molecules by hematopoietic cells is necessary and sufficient for selection of most V beta 8 DN cells. The lack of a role for class I expression by thymic epithelial cells suggests that the mechanism of selection of these cells by class I differs significantly from the mechanism of selection of conventional T cells. Models to explain the selection of these cells as well as their possible function in vivo are discussed. PMID- 8350061 TI - Functional GATA-3 binding sites within murine CD8 alpha upstream regulatory sequences. AB - Genes encoding the accessory molecules CD8 and CD4 are activated early in thymocyte development, generating CD4+8+ double positive intermediates, which give rise to two functionally distinct mature T cell subsets that express either CD4 or CD8. The mechanisms that govern the activation or suppression of the CD8 gene are likely to be central to the T cell development program. To identify the key regulatory factors, we have initiated an analysis of the transcriptional regulation of the murine CD8 alpha gene. We have identified three CD8+ cell specific DNAase I hypersensitive sites (HSS) located upstream of the murine CD8 alpha gene. In vitro mobility shift analysis of the -4.0-kb HSS region has revealed multiple binding sites for the T cell-restricted transcription factor GATA-3. In vitro translated murine GATA-3 binds specifically to both CD8 GATA sites, and coexpression of this factor in transient transfection assays transactivates a reporter construct containing these sequences. These results provide the first evidence for the role of a T cell-restricted factor in the regulation of either CD8 or CD4 genes. PMID- 8350062 TI - The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. AB - The expression of B lineage associated genes during early B cell differentiation stages is not firmly established. Using cell surface markers and multiparameter flow cytometry, bone marrow (BM) cells can be resolved into six fractions, representing sequential stages of development; i.e., pre-Pro-B, early Pro-B, late Pro-B/large Pre-B, small Pre-B, immature B, and mature B cells. Here we quantitate the levels of several B lineage associated genes in each of these fractions by RT-PCR, demonstrating different patterns of expression. We find that expression of terminal deoxynucleotidyl transferase (TdT), lambda 5, and VpreB is predominantly restricted to the Pro-B stages. Rag-1 and Rag-2 expression is also tightly regulated, and is found largely in the Pro-B through small Pre-B stages. Mb-1 is present from Pro-B throughout the pathway at high levels. Finally, Bcl-2 is expressed at high levels only at the pre-Pro-B and mature B stages, whereas it is low during all the intermediate stages. We also correlate this expression data with an analysis of the onset of Ig gene rearrangement as assessed by amplifying D-JH, VH-DJH, and VK-JK. Finally, we report differences in gene expression during B lymphopoiesis at two distinct ontogenic timings, in fetal liver and adult BM: both TdT and the precursor lymphocyte regulated myosin-like light chain are expressed at high levels in the Pro-B cell stage in bone marrow, but are absent from the corresponding fraction in fetal liver. In contrast, lambda 5, VpreB, Rag 1, and Rag-2 are expressed at comparable levels. PMID- 8350063 TI - Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection. AB - Previous studies have reported an association of gamma/delta T cells with microbial infection in both human lesions and murine infectious disease models. In this study we provide a comprehensive analysis of the conditions under which the induction of gamma/delta T cells occurs at a site of infection. We found a site-specific induction of gamma/delta T cells after the injection of Listeria monocytogenes in the peritoneal cavity of C3H mice. No changes were seen in the splenic or lymph node populations after these injections. Both the proportion and the absolute number of gamma/delta T cells increased in the peritoneal cavity. Additionally, when peritoneal T cells from Listeria-immune mice were restimulated in vitro, the induced gamma/delta T cells exhibited a greater expansion potential than the alpha/beta T cells. Neither the induced gamma/delta T cells nor those from normal mice expressed CD4 or CD8 on the cell surface. Thy-1 was expressed on only 29% of normal peritoneal gamma/delta T cells, but after intraperitoneal Listeria injection 65% of induced gamma/delta T cells expressed. Thy-1, Pgp-1 and CD45R expression on both normal and induced gamma/delta T cells was consistent with an activation phenotype. Significant increases in peritoneal gamma/delta T cells were not seen until 5-7 d after Listeria injection. The proportion of the CD3+ population expressing the gamma/delta T cell receptor remained elevated for 6-7 wk, while the absolute numbers of peritoneal gamma/delta T cells declined gradually over this time period, reflecting a decrease in both the number of lymphocytes and the percentage of these that were CD3+. Peak numbers of gamma/delta T cells were seen at day 10 with live microbes such as Listeria. A variety of microbes, toxins, mitogens, antigens, cytokines, and nonspecific inflammatory agents were evaluated for their ability to induce gamma/delta T cells in the peritoneal cavity. Both Gram-positive and Gram-negative bacteria as well as Mycobacteria were able to induce gamma/delta T cells that showed increased in vitro expansion potential. An exotoxin from a Gram-positive organism, listeriolysin-o, and the lipopolysaccharide (LPS) endotoxin from a Gram negative organism were also effective. gamma/delta T cell responses to LPS were under lps gene control. Peak numbers of gamma/delta T cells were observed at day 3 after injection with exotoxins and endotoxins. Modifications that abrogated the virulence of a bacterial strain also eliminated the inductive effect for gamma/delta T cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350065 TI - Control of Aedes dorsalis with sustained-release methoprene pellets in a saltwater marsh. AB - The efficacy and persistence of sustained-release methoprene (Altosid) pellets were evaluated in a tidal, saltwater marsh primarily against Aedes dorsalis. Pellets were applied prior to marsh inundation at 3.4 kg/ha. They provided > 99% control through the July and August high tide series (up to 42 days posttreatment), 86.4% control during the November high tide series (131 days posttreatment) and 66.6% control during the February high tide series (240 days posttreatment). Proportions of partially emerged adults increased over the course of the study, constituting 0, 0.7, 16.2 and 18.9% of the unsuccessfully emerging mosquitoes in July, August, November and February, respectively. Sixty-six percent of the completely emerged mosquitoes from the treated region of the marsh were found dead on the water surface, compared with only 0.7% from the control region. This implies that exposure to low concentrations of methoprene impairs the ability of the completely emergent mosquito to fly. PMID- 8350064 TI - Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells. AB - Peritoneal gamma/delta T cells from Listeria-immune mice show an enhanced potential to expand when restimulated with antigens or mitogens in vitro (see companion paper [Skeen, M. J., and H. K. Ziegler. 1993. J. Exp. Med. 178:971]). When cocultured with peritoneal alpha/beta T cells, the gamma/delta T cell population expanded preferentially even when the in vitro stimulus was specific for the alpha/beta T cell population. Purified gamma/delta T cells did not respond to alpha/beta T cell-specific stimuli. If isolated T cell subsets were recombined in cell mixing experiments, the resulting proliferative response was greater than additive. Irradiated alpha/beta T cells could enhance the proliferation of responding gamma/delta T cells, but the effect was unidirectional; i.e., irradiated gamma/delta T cells did not stimulate responding gamma/delta T cells. This effect appeared to be cytokine mediated and did not require cell-cell contact. Both recombinant interleukin 2 (rIL-2) and rIL-7 could support the expansion of the gamma/delta T cells, while rIL-7 was only minimally stimulatory for the alpha/beta T cells. The magnitude of the response by gamma/delta T cells to rIL-7 exceeded the response to other in vitro stimuli, including immobilized anti-T cell receptor monoclonal antibody, and was 50-100 fold greater than the alpha/beta T cell response to IL-7. This unique sensitivity of gamma/delta T cells to IL-7 was strongly enhanced by the presence of accessory cells. These cells could be replaced by rIL-1, establishing a synergy for IL-1 and IL-7 as factors that could uniquely stimulate this gamma/delta T cell population. Isolated peritoneal gamma/delta T cells from Listeria-immune mice react to heat-killed Listeria preparations in the presence of macrophages accessory cells in a non-H-2-restricted manner. Considered collectively, these results suggest a potential mechanism by which gamma/delta T cells can predominate in epithelial tissues and at sites of infection. PMID- 8350067 TI - Anthropophilic and zoophilic phlebotomine sand flies (Diptera, Psychodidae) from Thailand. AB - As a result of extensive surveys of sand flies carried out during 1987-90 in Thailand, species including a man-biter, Phlebotomus hoepplii, and cattle-biters, P. argentipes and P. major major, were discovered in Kanchanaburi Province. The human-baited catches revealed a low density of P. hoepplii and the biting occurred during 2100-2300 hours. Phlebotomus hoepplii was also found feeding on buffalo and inhabiting Pha-Thai Cave, Lampang Province. Phlebotomus argentipes was also a common cave-dweller and therefore had a wider distribution than P. major major, which was only collected in Sara Buri and Kanchanaburi provinces. The 3 species inhabited forest environments close to foothills and on stream banks. Although there is yet no evidence that they are involved in leishmaniasis transmission, the bionomics of the species are of importance and should be studied further. PMID- 8350066 TI - Isolation of Jamestown Canyon and snowshoe hare viruses (California serogroup) from Aedes mosquitoes in western Massachusetts. AB - Three isolates of Jamestown Canyon virus and one isolate of snowshoe hare virus (California serogroup) were obtained from adult Aedes females collected in western Massachusetts in 1982. Jamestown Canyon virus was isolated from Aedes abserratus/punctor once, and from Aedes intrudens twice. Snowshoe hare virus was isolated from Aedes stimulans group mosquitoes. La Crosse encephalitis (LAC) virus was not isolated from 1,552 adult Aedes triseriatus, nor from 22,557 Aedes triseriatus larvae. However, sera from 1/178 eastern chipmunks, 5/31 gray squirrels, and 8/144 white-tailed deer had neutralizing antibody to LAC virus. No sentinel rabbits placed at sites yielding virus isolates seroconverted to CAL viruses in either year. PMID- 8350069 TI - In situ hybridization mapping of histone genes in Anopheles albimanus. AB - The histone genes of Anopheles albimanus were mapped by in situ hybridization to 6 bands in Region 34A on the right arm of chromosome 3. A genomic library was made by cloning fragments of 15 to 23 kb (derived from partial EcoRI digestion) into the phage vector, EMBL4, and probed with the histone gene repeat of Drosophila melanogaster. Thirty-two phages containing histone gene sequences were isolated from about 10(5) plaque-forming units (pfu). Complete EcoRI digestion of DNA from 5 of the 32 recombinant phages and the genomic DNA of An. albimanus yielded a single 3.84-kb fragment that contained sequences homologous to the 5 histone genes of D. melanogaster. This 3.84-kb unit of mosquito histone genes was subcloned into puc19 plasmid, and the resulting clone (palbi34A) was used for in situ hybridization to salivary gland chromosomes. PMID- 8350068 TI - Evaluation of 1-octen-3-ol and carbon dioxide as black fly (Diptera: Simuliidae) attractants in Arkansas. AB - Carbon dioxide and 1-octen-3-ol were evaluated individually and in combination as black fly attractants. Significantly greater numbers of Cnephia pecuarum were collected in traps baited with CO2 and CO2 + octenol as compared with octenol alone or no bait. While greater numbers of C. pecuarum were collected in traps baited with the combination of CO2 and octenol as opposed to CO2 alone, results were only significantly different (P > or = 0.05) in one test. In contrast, significantly (P > or = 0.05) more adults of Simulium meridionale were collected in traps baited with CO2 alone. Octenol alone was not an effective attractant for the black fly species collected in the course of this study. In addition, use of octenol in conjunction with CO2 may impair representative sampling of black fly species present in a given area. PMID- 8350070 TI - Compatibility of cyclopoid copepods with mosquito insecticides. AB - Larvivorous copepods (Macrocyclops, Mesocyclops and Acanthocyclops) were tested for their sensitivities to commonly used mosquito larvicides and adulticides. The cyclopoids were not harmed by Bacillus thuringiensis (H-14) (B.t.i.) or larviciding oil. Control of mosquito larvae in field trials was accelerated by applying B.t.i. at the same time cyclopoids were introduced to a breeding site. Among adulticides tested, the cyclopoids were least sensitive to permethrin. Field trials demonstrated that permethrin does not harm cyclopoids when applied at label specifications. PMID- 8350071 TI - Small plot evaluation of a sustained-release sand granule formulation of methoprene (SAN 810 I 1.3 GR) for control of Aedes Taeniorhynchus. AB - A sand granule formulation of methoprene (SAN 810 I 1.3 GR) was tested in outdoor intermittently flooded pools as a pre- and postflood treatment for the control of Aedes taeniorhynchus. In field test 1, pre- and postflood treatments were equally effective. Inhibition of emergence in mosquitoes exceeded 90% for one and 3 flood/dry cycles when SAN 810 I 1.3 GR was applied at rates of 2.8 and 5.6 kg/ha, respectively. In field test 2, > 90% inhibition of emergence was achieved only when SAN 810 I 1.3 GR was applied postflood at 5.6 kg/ha. PMID- 8350072 TI - Effect of photoperiod on longevity and metabolic rate in Anopheles quadrimaculatus. AB - The effect of photoperiod on longevity of nondiapausing members of a species in the mosquito species complex Anopheles quadrimaculatus was tested in laboratory experiments. First-generation adults reared from 2 field collections showed the same trends: those reared under short photoperiod (8 h light: 16 h dark) lived longer than did those reared under long photoperiod (16 h light: 8 h dark). Adult metabolic rates were not consistently related to longevity. In adults reared from the first collection, metabolic rates were higher in long-photoperiod individuals but in adults reared from the second collection, metabolic rates were higher in short-photoperiod individuals. Longevity appears to be another of many insect features that are affected similarly by temperature and photoperiod. PMID- 8350073 TI - Mating and nutritional state affect the reproduction of Aedes albopictus mosquitoes. AB - Mated female Aedes albopictus mosquitoes that were maintained after emergence without carbohydrate were more likely to develop eggs after a small blood meal than were unmated females maintained on the same diet. The effect was due to male accessory gland substances transferred to the female during mating. Neither the endogenous reserves of protein and lipid nor the number of eggs developed per volume of ingested blood differed between mated and unmated females, suggesting that the utilization of existing reserves was altered by mating. Methoprene administered to both mated and unmated females that ingested small blood meals reduced the likelihood that egg development would occur. Small volumes of blood were more likely to trigger oogenesis in both mated and unmated females if their abdomens were additionally distended. PMID- 8350074 TI - Runnelling to control saltmarsh mosquitoes: long-term efficacy and environmental impacts. AB - Aedes vigilax is a problem mosquito species prevalent in subtropical Australian coastal wetlands. We evaluate the long-term impacts of runnelling, an environmentally benign habitat modification method, on mosquitoes and the wetland environment. Runnelling uses shallow channels to enhance flushing of the marsh. The method successfully reduced larval numbers to below nuisance levels for the 6.5 year study period. We did not detect any significant difference in the wetland environment between runnelled and unmodified parts of the study area. However, the spatial extent of the effects may have extended beyond the modified area. PMID- 8350075 TI - Field evaluations in malaise and canopy traps of selected targets as attractants for tabanid species (Diptera: Tabanidae). AB - Various configurations of an inflated vinyl beach ball covered with black fabric were evaluated in Malaise and canopy (modified Manitoba) traps for possible use as an insecticide-impregnated visual target (T) for Tabanidae. In Malaise traps, T attracted 2x more flies than no T. When inflated with carbon dioxide, T was not significantly different from T filled with air, no matter which type of trap it was in. In canopy traps, 2 or 4 white spots applied to T did not increase its attractiveness to tabanids. When treated with octenol, T was 2-5x more attractive than an untreated T in canopy traps. However, when an octenol treatment was aged for 48 h, it was less effective than a fresh treatment. Overall, the 3 most frequently collected species, in order of abundance, were: Tabanus lineola hinellus, Hybomitra vicina and Chrysops atlanticus. Significantly more T. l. hinellus and H. vicina were collected at T with octenol than at T without octenol. Attempts to detect an insecticidal effect on flies captured in both types of trap that had been baited with Ts treated with permethrin were unsuccessful. PMID- 8350076 TI - Unreliable supply of potable water and elevated Aedes aegypti larval indices: a causal relationship? AB - We investigated the hypothesis that a deficient supply of piped water was causing a high prevalence of water storage containers, which in turn, become important aquatic habitats of Aedes aegypti in a small town in Venezuela. The House (71.2%) and Breteau indices (229) were considerably elevated. Prevalent positive containers were: metal drums, small disposable containers (bottles, tins, etc.), tires, house plants (flowers in vases and plants in pots with earth) and tanks. Most people reported frequent interruptions in the supply of piped water and considered it to be unreliable. The frequency of interruptions in the supply of water was positively correlated with the House and Container indices, and with the number of positive containers, water-storage devices and positive water storage devices per house. Even people who considered that they had an adequate supply of water kept numerous water storage containers. Most people (60%) said they would not stop storing water even in the event of the establishment of a reliable supply of piped water. PMID- 8350077 TI - Identification of blood meals in Aedes aegypti by antibody sandwich enzyme-linked immunosorbent assay. AB - A comparative study of 3 ELISA protocols was performed for host blood meal identification in Aedes aegypti. In the sandwich-B ELISA, which used a combination of heavy and heavy+light chain conjugates, specificity was improved to such a degree that conjugates no longer required cross-adsorption with heterologous sera. Using the sandwich-B assay, human blood meals in laboratory reared Ae. aegypti could be detected longer after feeding (100% at 32 h and 80% at 42 h) than with a direct assay (100% at 20 h). Efficacy of the sandwich-B and direct ELISAs in field analyses was studied in parallel) using 80 field collected mosquitoes from Thailand. The sandwich-B assay was superior (88% detection rate) to the direct assay (41% detection rate) and was thus selected as the method of choice for future field studies. PMID- 8350078 TI - Indoor low-volume insecticide spray for the control of Anopheles albimanus in southern Mexico. Village-scale trials of bendiocarb, deltamethrin and cyfluthrin. AB - A comparative insecticide village-scale trial was carried out to determine the efficacy of low-volume (LV) indoor spray of bendiocarb, deltamethrin and cyfluthrin for the control of Anopheles albimanus in a coastal plain of southern Mexico. Low-volume spray was conducted with knapsack mist-blowers, giving an average discharge rate of 215 ml/min, which deposited droplets of 50-100 microns. Using this technique, 25 houses were treated/sprayman/day as compared with 8 houses/sprayman/day using conventional hand compression pumps. Indicators of LV mortality showed a residual activity of 10 wk as compared with 13 wk of activity for wettable powder (WP) (bendiocarb). When comparing expenditures, LV spray costs were 43% less when using bendiocarb, 83% less with deltamethrin and 74% less with cyfluthrin with respect to the conventional WP spray of the same insecticides. Low-volume spray time was reduced by one-third, with respect to WP. Malaria incidence was reduced by 53 and 56%, respectively, in the bendiocarb LV and deltamethrin LV treated villages as compared with the untreated village. PMID- 8350079 TI - Investigations on possible resistance in Aedes vexans field populations after a 10-year application of Bacillus thuringiensis israelensis. AB - In the Upper Rhine Valley (Germany), Bacillus thuringiensis var. israelensis has been widely used against floodwater mosquitoes over an area of approximately 500 km2 for more than 10 years. The susceptibility of larvae of Aedes vexans field populations in 3 untreated (Lake Constance) and 3 treated areas (Upper Rhine Valley) was assessed by means of bioassays with B.t.i. (Bactimos WP, 6,000 AAU/mg), following WHO guidelines. Log-probit analyses and statistical evaluations of the data showed that the LC50 values as well as slopes of bioassays of the larvae deriving from the different areas showed no significant differences. Two populations in the treated area were even more susceptible than populations from the untreated areas. These results have been confirmed by resistance ratios, which were less than one in all tests carried out. PMID- 8350080 TI - Bloodfeeding behavior of Anopheles gambiae s.l. and Anopheles funestus in Kilifi District, Kenya. AB - Blood meal samples were tested by ELISA for 534 Anopheles gambiae s.l. and 76 Anopheles funestus collected from 25 sites in Kilifi District, Kenya. Human IgG was detected in 94.4% of the An. gambiae s.l. and in 90.8% of the An. funestus. No samples were positive for cow and only a few were positive for goat. Both species fed predominantly on humans irrespective of host availability. At these sites on the Kenyan coast, the high degree of human-feeding by malaria vectors contributes to the efficiency of malaria parasite transmission and the high incidence of severe malaria. PMID- 8350081 TI - Application of radar rainfall estimates for surveillance of Aedes taeniorhynchus larvae. AB - A preliminary investigation of land-based radar rainfall estimates for surveillance of Aedes taeniorhynchus larvae was conducted from January 1 to May 21, 1991 in Collier County, FL. Rainfall estimates from the National Weather Service RADAP II radar system, supplemented with tide gauge data, served as criteria for larval inspection. Rain, rain+tide and tide, respectively, triggered 48, 26 and 26% of the 14 proposed inspection trips. This system detected 7/8 larval broods found by Collier Mosquito Control District surveillance; the only brood not detected consisted of stragglers from an earlier brood exposed to cool weather and methoprene. A QUICKBASIC program that extracts Cartesian coordinates and rainfall estimates from RADAP II B-SCAN data was developed. PMID- 8350082 TI - Temperature and flow rate effects on mass median diameters of thermally generated malathion and naled fogs. AB - The effects of temperature and flow rate on mass median diameters (mmds) of thermally generated aerosol clouds were studied. Number 2 fuel oil alone, undiluted and diluted malathion 91, and undiluted naled were examined. There was a significant flow rate x temperature interaction on the mmds of diluted malathion fogs: i.e., differences among flow rates depended on temperature and vice versa. PMID- 8350083 TI - Survey of dirofilariasis in Arkansas. AB - A card survey was sent to 340 veterinarians in the Urban, Delta, Highland and Coastal Plain regions of Arkansas. Veterinarians were asked to indicate numbers of dogs tested, confirmed Dirofilaria immitis positive, diagnostic techniques, frequency and period tested. A significantly greater percentage of dogs tested D. immitis positive in the Delta region as compared with the Urban region. There were no significant differences in the percentage of treated dogs on prophylaxis or the types of diagnostic tests among regions. PMID- 8350084 TI - Aedes aegypti in New Jersey. PMID- 8350085 TI - Structures of sesquiterpene polyol esters from Celastrus stephanotiifolius with potential tumor-promotion inhibitor activity. AB - Esters of eight new ([1],[4-6], and [8-11]) and five known sesquiterpenenoid polyalcohols have been isolated from Celastrus stephanotiifolius. Their structures were established on the basis of chemical reactions and spectral analysis. The structural elucidation indicated that the structures of some related compounds should be revised. The isolated sesquiterpenes were observed to inhibit Epstein-Barr virus early antigen activation significantly at low doses. PMID- 8350086 TI - Studies on inhibitors of skin tumor promotion, XII. Rotenoids from Amorpha fruticosa. AB - As a part of screening studies for chemopreventive agents (anti-tumor-promoters), six North American plants belonging to the Amorpha genus were tested using an in vitro assay system. Of these plants, Amorpha fruticosa exhibited strong inhibitory effects on Epstein-Barr virus early antigen (EBA-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Also six rotenoids, amorphispironone [1], tephrosin [2], amorphigenin [3], 12a hydroxyamorphigenin [4], 12a-hydroxydalpanol [5], and 6'-O-D glucopyranosyldalpanol [6], were isolated from the leaves of A. fruticosa. Among these retenoids, 1 and 2 exhibited remarkable inhibitory effects of EBV-EA activation induced by TPA. Further, 1 and 2 exhibited significant anti-tumor promotion effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These investigations suggested that these rotenoids might be valuable anti-tumor-promoters. PMID- 8350087 TI - Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. AB - A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay. Artemisinin [1] had an IC50 value of 29.8 microM. Derivatives of dihydroartemisinin [2], being developed as antimalarial drugs (artemether [3], arteether [4], sodium artesunate [5], artelinic acid [6], and sodium artelinate [7]), exhibited a somewhat more potent cytotoxicity. Their IC50 values ranged from 12.2 to 19.9 microM. The presence of an exocyclic methylene fused to the lactone ring, as for artemisitene [9], led to higher cytotoxicity than 1. From the two epimeric 11-hydroxyartemisinin derivatives, the R form 12 showed a considerably higher cytotoxicity than the S form 13. Opening of the lactone ring of 1 dramatically reduced the cytotoxicity. The ether dimer 8 of 2 was the most potent cytotoxic agent, its IC50 being 1.4 microM. The variations in cytotoxicity between the structurally related compounds mostly correlated well with the theoretical capacity of radical formation and stabilization. In some cases lipophilicity or the presence of an electrophilic moiety seemed to have a determinant influence on cytotoxicity. The artemisinin-related endoperoxides showed cytotoxicity to EAT cells at higher concentrations than those needed for in vitro antimalarial activity, as reported in the literature. PMID- 8350088 TI - A novel amino acid glycoside and three amino acids from Allium sativum. AB - A novel amino acid glycoside (-)-N-(1'-deoxy-1'-beta-D-fructopyranosyl)-S-allyl-L cysteine sulfoxide [1], was isolated from a hydrophilic extract of the leaves of Allium sativum (Alliaceae), together with three known compounds: (+)-S-allyl-L cysteine sulfoxide [2],(+)-S-methyl-L-cysteine sulfoxide [3], and (+)-S-(trans-1 propenyl)-L-cysteine sulfoxide [4]. The latter two substances were isolated for the first time from garlic. The structure elucidation of 1 was performed by extensive chemical, spectroscopic (ir, fabms, 1D and 2D(1)H- and (13)C-nmr measurements) and chromatographic experiments. For the first time, detailed nmr data and the unambiguous assignment of all (13)C-nmr data for compounds 2-4 were reported. Compound 1, the amino acid glycoside, revealed a significant inhibition of in vitro platelet aggregation induced by ADP and epinephrine, whereas none of the amino acids tested displayed any activity. PMID- 8350089 TI - 30-, 31-, and 32-hydroxybullatacinones: bioactive terminally hydroxylated annonaceous acetogenins from Annona bullata. AB - From Annona bullata, three more pairs of new ketolactone Annonaceous acetogenins were isolated by bioactivity-directed isolation. They are hydroxylated adjacent bistetrahydrofuran (THF) acetogenins and are named (2,4-cis and trans)-32 hydroxybullatacinone (1 and 2), (2,4-cis and trans)-31-hydroxybullatacinone (3 and 4), and (2,4-cis and trans)-30-hydroxybullatacinone (5 and 6). The structures were elucidated by analysis of the 1H- and 13C-nmr spectra of 1-6 and their acetates and the ms of their tri-trimethylsilyl (TMSi) derivatives as compared with bullatacinone [7]. This is the first time that Annonaceous acetogenins with OH groups at successive positions near the end of the aliphatic chain have been reported. All of the new compounds showed potent activities in the brine shrimp lethality test and against human solid tumor cells in culture, with selectivities exhibited especially toward the colon cancer cell line (HT-29). PMID- 8350090 TI - Isolation of a dihydrobenzofuran lignan from South American dragon's blood (Croton spp.) as an inhibitor of cell proliferation. AB - Dragon's blood is a red viscous latex extracted from the cortex of various Croton spp. (Euphorbiaceae), most commonly Croton lechleri, Croton draconoides (or Croton palanostigma), and Croton erythrochilus. It is used in South American popular medicine for several purposes, including wound healing. Bioassay-guided fractionation of dragon's blood, using an in vitro test system for the stimulation of human umbilical vein endothelial cells, has resulted in the isolation of a dihydrobenzofuran lignan, 3',4-O-dimethylcedrusin or 4-O methyldihydrodehydrodiconiferyl alcohol [2-(3',4'-dimethoxyphenyl)-3 hydroxymethyl-2,3-dihydro-7-methoxybenzo furan-5- propan-1-ol] [1] as the biologically active principle. A related compound, 4-O-methylcedrusin [2-(3',4' dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzo furan-5- propan-1-ol] [2], and the alkaloid taspine [3], also isolated from dragon's blood, were not active in the same assay. A cell proliferation assay, measuring the incorporation of tritiated thymidine in endothelial cells, showed that compound 1 did not stimulate cell proliferation, but rather inhibited thymidine incorporation, while protecting cells against degradation in a starvation medium. PMID- 8350091 TI - The structures of aplysinamisines I, II, and III; new bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina cauliformis. AB - Three new bromotyrosine-derived alkaloids, aplysinamisines I [4], II [5], and III [6], were isolated from the sponge Aplysina cauliformis collected in Puerto Rico and their chemical structures elucidated on the basis of spectroscopic methods. Compounds 4-6 showed marginal antimicrobial activity, and aplysinamisines II [5] and III [6] displayed modest cytotoxicity. PMID- 8350092 TI - Evaluation of marine sponge metabolites for cytotoxicity and signal transduction activity. AB - Twenty-four metabolites derived from marine sponges were evaluated for their cytotoxicities against two human tumor cell lines, non-small cell lung carcinoma A549 and colon adenocarcinoma HT-29, and against one murine leukemia cell line, P 388, and evaluated for their ability to effect signal transduction in a newly developed cell adhesion assay using an EL-4 cell line. The compounds included latrunculin A [1], batzelline A [2], chondrillin [3], aureol [4], epihippuristanol, theonellamine B, discorhabdins A and C, kabiramide C, dercitin, meridine, manzamines A, B, and C, 8,15-diisocyano-11(20)-amphilectene and the corresponding C-15 formamide, a 20-carbon acetylenic alcohol, 4,5-dihydro-6" deoxybromotopsentin, epispongiadiol, isospongiadiol, puupehenone, reiswigin A, and demethyl- and demethyloxyaaptamine. Latrunculin A [1], batzelline A [2], chondrillin [3], and aureol [4] expressed the desired profile of a greater than five-fold level of cytotoxicity against A549 relative to P-388, and an effect in the cell adhesion assay. In this group of compounds, cytotoxicity toward A549 was equal to or more pronounced than against HT-29. Latrunculin A was evaluated in an sc-implanted human A549 lung tumor xenograft mouse model and yielded a T/C of 146%. Batzelline A was evaluated in the cancer cell line panel at the National Cancer Institute and found to express selective cytotoxicity against several melanoma cancer cell lines. PMID- 8350093 TI - Bioactive and other sesquiterpenoids from Porella cordeana. AB - Bioassay-directed fractionation of the MeCOEt extract of Porella cordeana yielded drimenin [1] and aristolone [4], which were moderately toxic towards DNA-repair deficient mutants of Saccharomyces cerevisiae. Three inactive sesquiterpenes, 7 ketoisodrimenin [2], 7-ketoisodrimenin-5-ene [3], and norpinguisanolide, were also obtained. Compounds 2 and 3 are new. PMID- 8350095 TI - Two novel steroidal glycoside sulfates from the starfish Cosmasterias lurida. AB - Two novel steroidal monoglycoside sulfates, luridosides A [1] and B [2], have been isolated from the starfish Cosmasterias lurida. These compounds co-occur with one known steroidal monoglycoside, pycnopodioside C [3]. The structures of the new metabolites were determined from spectral data and comparison with those of related steroids. PMID- 8350094 TI - Antiplatelet effects and vasorelaxing action of some constituents of Formosan plants. AB - Various xanthones as well as quercetin have been shown to exhibit antiplatelet activity. A series of anthraquinones analogues structurally related to xanthones and a series of quercetin-related compounds were tested for their antiplatelet effects. Emodin, frangulin B, kaempferol tetraacetate, quercetin-3-O-galactoside octaacetate, rhamnazin triacetate, and rhamnetin tetraacetate were found to be potent antiplatelet agents, and 1,8-dihydroxy-6-methoxy-3-methylanthraquinone 8-O rhamnosyl-(1-->2)-glucoside, rhamnustrioside undecaacetate, rutin decaacetate, and quercetin-3-O-(6-O-alpha-L-arabinopyranosyl)-beta-D-galactopyranos ide decaacetate showed significant antiplatelet effects. Quercetin showed vasorelaxing action in rat thoracic aorta. PMID- 8350096 TI - Flavonoids from Koelreuteria henryi and other sources as protein-tyrosine kinase inhibitors. AB - The EtOH extract of Koelreuteria henryi was investigated in a search for natural products with potential protein-tryrosine kinase (PTK) inhibitory activity. The PTK inhibitory activity of the crude fractions was determined by measuring their inhibition of p56lck partially purified from bovine thymus using angiotensin I as a substrate. Analysis of those fractions that exhibited significant activity led to the isolation of kaempferol and quercetin, in addition to two kaempferol glycosides, kaempferol-O3-alpha-rhamnopyranoside [1] and kaempferol-O3-alpha arabinopyranoside [2]. This study represents the first report on the isolation of flavonols and their PTK inhibitory activities from the genus Koelreuteria. Eight other flavonoids were also examined to study the role of the hydroxy groups on the B ring on PTK inhibitory activity. PMID- 8350098 TI - Pieter Camper (1721-89). PMID- 8350097 TI - A combined clinical and neurophysiological approach to the study of patients with tremor. PMID- 8350100 TI - Reductions in parietal and temporal cerebral metabolic rates for glucose are not specific for Alzheimer's disease. AB - Reduction in the regional cerebral metabolic rate for glucose (rCMRglc) in the parietal and temporal regions has been shown in Alzheimer's disease (AD). The specificity of these findings for this disease state is uncertain. We repeatedly measured rCMRglc with positron emission tomography and [18F]2-fluoro-2-deoxy-D glucose in the resting state in a 68 year old man with slowly progressive dementia who, during life, was initially diagnosed as having dementia of the Alzheimer type, then Parkinson disease with dementia, but was found to have only Parkinson's disease at necropsy. Metabolic ratios (rCMRglc/mean grey CMRglc) were significantly (p < 0.05) reduced in parietal and temporal regions, as well as in the prefrontal and premotor areas. This pattern was similar in regional distribution and magnitude of the defect to that seen in patients with probable AD. These results suggest that reductions of glucose metabolism in association neocortex in AD are not specific to the disease process, but may be related to the dementia state. PMID- 8350101 TI - Successful treatment of childhood onset symptomatic dystonia with levodopa. AB - Three patients with childhood onset symptomatic dystonia responded to levodopa. None fulfilled criteria for a diagnosis of "dopa responsive dystonia" (Segawa's disease). One may have had athetoid cerebral palsy for almost 25 years. All obtained dramatic and sustained benefit from levodopa therapy. A therapeutic trial of levodopa is advised in all patients in whom dystonia has developed in childhood or early adult life, regardless of suspected aetiology or duration of symptoms. PMID- 8350099 TI - Management of raised intracranial pressure. AB - This review has been written at an unfortunate time. Novel questions are being asked of the old therapies and there is an abundance of new strategies both to lower ICP and protect the brain against cerebral ischaemia. In the United Kingdom, the problem is to ensure that appropriate patients continue to be referred to centres where clinical trials of high quality can be undertaken. One of the success stories of the past decade has been the decline in the number of road accidents as a result of seat belt legislation, improvements in car design and the drink/driving laws. Hence, fortunately there are fewer patients with head injuries to treat and it is even more important that patients are appropriately referred if studies to assess efficacy of the new strategies are not to be thwarted. The nihilistic concept that intensive investigation with ICP monitoring for patients with diffuse head injury or brain swelling following evacuation of a haematoma or a contusion has no proven beneficial effect on outcome, requires revision. A cocktail of therapies may be required that can be created only when patients are monitored in sufficient detail to reveal the mechanisms underlying their individual ICP problem. Ethical problems may arise over how aggressively therapy for intracranial hypertension should be pursued and for how long. There has always been the concern that cranial decompression or prolonged barbiturate coma may preserve patients but with unacceptably severe disability. Some patients may be salvaged from herniating with massive cerebral infarction with the use of osmotherapy but is the outcome acceptable? Similar considerations apply to some children with metabolic encephalopathies. Where such considerations have been scrutinised in patients with severe head injury, the whole spectrum of outcomes appears to be shifted so that the number of severe disabilities and persistent vegetative states are not increased. However, it is important to be sensitive to such issues based on experience of the particular cause of raised intracranial pressure in a given age group. PMID- 8350102 TI - Assessing tremor severity. AB - A clinical rating scale which measured the severity of tremor in 20 patients (12 with essential tremor and 8 with "dystonic" tremor) was assessed at specific anatomical sites for both inter and intra-rater reliability using four raters. The scores obtained with the scale were compared with the results of upper limb accelerometry, an activity of daily living self-questionnaire and estimates of the tremor induced impairment in writing and drawing specimens. The results show that, for the purposes of routine assessment and therapeutic trials, a clinical rating scale can produce reliable results which are a more valid index of tremor induced disability than standard postural accelerometry. PMID- 8350103 TI - Diurnal effects of motor activity and fatigue in Parkinson's disease. AB - Wrist motor activity was monitored continuously in 65 patients with Parkinson's disease (PD) to assess the influence of disease severity and excessive fatigue on the diurnal motor activity pattern. Mildly or moderately affected PD patients had a similar diurnal pattern to that of 68 healthy controls, with a late morning peak; however, mean levels of motor activity were lower. The most severely affected patients showed an overall flattened diurnal pattern. Results refute the existence of end of day deterioration, but instead suggest a "depressed morning start" in the most severely affected patients with PD. Excessive fatigue was not reported at a particular time of day and did not influence the diurnal motor activity pattern. PMID- 8350104 TI - Neuropsychological abnormalities in AIDS and asymptomatic HIV seropositive patients. AB - Neuropsychological and immunological parameters were studied in 36 AIDS patients with early disease and without clinical, laboratory, and neuroradiological signs of CNS impairment, and also in 33 asymptomatic HIV seropositive subjects. Many AIDS patients performed abnormally on timed psychomotor tasks, tasks involving sequencing and "set-shifting", and memory tasks stressing attention, learning, active retrieval, and monitoring of information. Asymptomatic HIV seropositive subjects as a group did not perform significantly worse than controls. However, on the basis of a cut off number of pathological performances on neuropsychological tasks, 52.8% of AIDS and 30.3% of asymptomatic HIV seropositive subjects had cognitive impairment, compared with 3.9% of HIV seronegative controls. Low values of CD4+ cells and of CD4+/CD8+ ratio and high titres of P-24 antigen in the blood prevailed among subjects with cognitive impairment, especially in the asymptomatic HIV seropositive group. PMID- 8350105 TI - Bilateral occipital calcification, epilepsy and coeliac disease: clinical and neuroimaging features of a new syndrome. AB - Twenty patients affected by bilateral occipital cortical-subcortical calcification (BOC) are described, 19 (95%) had epilepsy. In 8 of 16 cases studied, intestinal biopsy revealed coeliac disease. Fourteen patients had occipital partial epilepsy with a relatively benign outcome, while 4 patients were affected by a severe form of epilepsy, with very frequent, drug-resistant, generalised and partial seizures with mental deterioration. One patient had a single episode of convulsive status epilepticus at four months of age. The neurological examination was normal in all patients. CT showed flocculo-nodular, cortico-subcortical BOC, without enhancement and without lobar or hemispheric atrophy. MRI was normal. The clinical and neuroimaging features of these patients are different therefore from those with the Sturge-Weber Syndrome. The study confirms a high prevalence of coliac disease in patients with BOC, but the relationship between these two pathologies still needs to be clarified. PMID- 8350106 TI - Compressive radial nerve palsy induced by military shooting training: clinical and electrophysiological study. AB - Ten recruited soldiers developed acute left wrist drop and numbness on the back of the thumb after a three hour military shooting training. Neurological examination disclosed decreased muscle power (0-2/5) of left wrist dorsiflexion, hypalgesia and hypaesthesia on the radial side of the left hand, and diminished brachioradialis reflex. Electrophysiological studies showed prolonged distal latency, reduced amplitude and slowness of left radial nerve motor conduction velocity between the axilla and elbow. Electromyography (EMG) revealed fibrillation potentials at rest, polyphasic motor unit and an incomplete interference pattern at volition over the extensor digitorum communis and brachioradialis. Nine patients recovered completely clinically and electrophysiologically between nine and 12 weeks after the onset of the palsy. Sensation recovered faster than the weakness. One patient failed to recover after three months, possibly because of the longer duration of nerve compression. Longer nerve compression time and sustained, decreased muscle power with signs of active denervation in EMG are indicators of poor prognosis. PMID- 8350107 TI - Excessive closure of the right eye: a new sign of infarction in the territory of the ipsilateral right middle cerebral artery. AB - In right middle cerebral territory infarction a new sign, excessive closure of the right eye ipsilateral to the lesion and mild closure of the left eye on command, was noted. The excessive ipsilateral eye closure was not observed on spontaneous eye closure. PMID- 8350108 TI - Horner's syndrome in Wegener's granulomatosis: report of four cases. AB - Four patients with active Wegener's granulomatosis had Horner's syndrome, which was the only neurological involvement in one. Two others had multiple mononeuropathy and one a multiple cranial neuropathy. Horner's syndrome occurred in the active stage and improved with treatment of Wegener's granulomatosis. PMID- 8350109 TI - Mitochondrial encephalomyopathy: variable clinical expression within a single kindred. AB - The clinical manifestations of mitochondrial encephalomyopathy are described in four generations of a single kindred. The age of onset of major neurological disturbance varied from 3-70 years. In some patients, deafness was the only manifestation; in others, recurrent bouts of status epilepticus associated with focal neurological deficits and headache, caused severe disability or death. Examples of all three adult forms of mitochondrial encephalomyopathy: MELAS, MERFF and Kearns Sayre syndrome, were represented within the kindred. Associated features included deafness, short stature, non-insulin-dependent diabetes mellitus, migraine, peptic ulceration and severe constipation. The nt 3243 A-G MELAS mutation was detected in two members of the kindred. This study highlights the diversity of clinical expression of a mitochondrial mutation within a single kindred. PMID- 8350110 TI - Transcranial Doppler detection of anterior cerebral artery vasospasm. AB - The performance of transcranial Doppler in the detection of anterior cerebral artery vasospasm and vasospasm in patients after subarachnoid haemorrhage was analysed. Transcranial Doppler and cerebral angiography were performed within the same 24 hours on each of 41 patients with acute subarachnoid haemorrhage. Sensitivity and specificity of transcranial Doppler to classify middle cerebral arteries, anterior cerebral arteries, and patients with angiographic vasospasm were determined at mean velocities of 120 and 140 cm/s. Accuracy of transcranial Doppler was better at 140 than at 120 cm/s. For the middle cerebral artery, sensitivity was 86%, specificity 98%. For the anterior cerebral artery, sensitivity was 13%, specificity 100%. Among all patients, sensitivity was 45%, specificity 96%. Among patients with anterior communicating artery aneurysms, sensitivity was 14%, specificity 90%. Therefore, transcranial Doppler accurately differentiates between middle cerebral arteries with and without vasospasm on angiography, but has a very low sensitivity for detecting anterior cerebral artery vasospasm and vasospasm in patients with anterior communicating artery aneurysms. Since vasospasm may involve anterior cerebral arteries while sparing middle cerebral arteries, especially after rupture of an anterior communicating artery aneurysm, caution should be exercised in using negative transcranial Doppler results to make treatment decisions based on the assumed absence of vasospasm. PMID- 8350111 TI - Sir Charles Bell 1774-1842. PMID- 8350112 TI - Angiotropic intravascular large-cell lymphoma with massive cerebral extension. AB - Angiotropic intravascular large-cell lymphoma (AILL) is a rare, generally fatal disease characterised by a multifocal proliferation of neoplastic mononuclear cells within small blood vessels. The diagnosis of a patient was made at necropsy. The malignant cells had infiltrated the periventricular areas of the brain. PMID- 8350113 TI - Acute disseminated encephalomyelitis presenting as a solitary brainstem mass. AB - A 36 year old woman presented with a subacute brainstem syndrome. MRI showed a solitary, gadolinium enhancing brainstem mass, which on biopsy showed perivenous inflammation and demyelination compatible with acute disseminated encephalomyelitis. PMID- 8350114 TI - Pure progressive aphemia. AB - Aphemia, also called anarthria or severe apraxia of speech, is a rare disorder of speech production usually resulting from vascular lesions affecting the inferior premotor cortex of the left hemisphere. A patient presenting with aphemia as the sole manifestation of primary progressive aphasia (PPA) is reported. PMID- 8350115 TI - Vigabatrin and depression. AB - Ten patients who developed a major depressive episode in association with vigabatrin treatment for intractable epilepsy are reported. The depression usually occurred early in the course of treatment, but when delayed followed a recent increase in dose. Depressive symptoms occurred at doses varying between 1.5 g and 4 g a day, often but not always when patients were experiencing a decrease in their seizure frequency. Most patients had a history of affective disturbance, sometimes in association with other GABAergic drugs. The observations support a possible role for GABAergic mechanisms in the biology of mood disorders. PMID- 8350116 TI - Dementia with leucoaraiosis and dural arteriovenous malformation: clinical and PET case study. AB - A case of rapidly progressive dementia with diffuse leucoaraiosis on CT was attributable to a supratentorial dural arteriovenous malformation. Positron emission tomography (PET) showed low cerebral blood flow and high oxygen extraction ratio throughout the cerebral hemispheres indicating a state of chronic haemodynamic compromise which could predispose to the development of a vascular dementia. CT images of dilated intracerebral veins suggested that a venous drainage overload rather than a vascular steal phenomenon might be involved in the pathophysiology of the dementia of vascular origin. PMID- 8350117 TI - Syndrome of transtentorial herniation: is vertical displacement necessary? AB - MRI from a comatose patient with a massive acute subdural haematoma showed most of the features of transtentorial herniation described in the classic pathology literature. In addition to encroachment on the perimesencephalic cisterns, infarction in the anterior and posterior cerebral artery territories, ischaemic change in the lower diencephalon, and ventricular enlargement were visualised. Despite the clinical syndrome and these secondary changes due to compression, there was only approximately 2 mm of downward displacement of the upper brainstem compared with 13 mm horizontal displacement. Although tissue shifts adjacent to the tentorial aperture cause brainstem and vascular compression, these changes may occur with minimal downward herniation. PMID- 8350118 TI - 'Pinocchio syndrome': a peculiar form of reflex epilepsy? PMID- 8350119 TI - Acute non-lymphoblast leukaemia presenting as a Guillain-Barre syndrome. PMID- 8350120 TI - Polyunsaturated fatty acids in peroxisomal disorders: a hypothesis and a proposal for treatment. PMID- 8350121 TI - Herpes simplex encephalitis in a patient with complex partial epilepsy: confirmation by the polymerase chain reaction with necropsy studies. PMID- 8350122 TI - Accuracy of clinical diagnosis of idiopathic Parkinson's disease. PMID- 8350123 TI - Memory representations underlying motor commands used during manipulation of common and novel objects. AB - 1. While subjects lifted a variety of commonly handled objects of different shapes, weights, and densities, the isometric vertical lifting force opposing the object's weight was recorded from an analog weight scale, which was instrumented with high-stiffness strain gauge transducers. 2. The force output was scaled differently for the various objects from the first lift, before sensory information related to the object's weight was available. The force output was successfully specified from information in memory related to the weight of common objects, because only small changes in the force-rate profiles occurred across 10 consecutive lifts. This information was retrieved during a process related to visual identification of the target object. 3. The amount of practice necessary to appropriately scale the vertical lifting and grip (pinch) force was also studied when novel objects (equipped with force transducers at the grip surfaces) of different densities were encountered. The mass of a test object that subjects had not seen previously was adjusted to either 300 or 1,000 g by inserting an appropriate mass in the object's base without altering its appearance. This resulted in either a density that was in the range of most common objects (1.2 kg/l) or a density that was unusually high (4.0 kg/l). 4. Low vertical-lifting and grip-force rates were used initially with the high-density object, as if a lighter object had been expected. However, within the first few trials, the duration of the loading phase (period of isometric force increase before lift off) was reduced by nearly 50% and the employed force-rate profiles were targeted for the weight of the object.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350125 TI - Gustatory neural coding in the amygdala of the alert macaque monkey. AB - 1. Neurons in the amygdala are implicated in mediating hedonic appreciation, emotional expression, and conditioning, particularly as these relate to feeding. The amygdala receives projections from the primary taste cortex in monkeys, offering a route by which it could gain access to the gustatory information required to guide feeding behavior. We recorded the activity of 35 neurons in the amygdala of alert rhesus macaques in response to a range of gustatory intensities and qualities to characterize taste-evoked activity in this area. 2. The stimulus array comprised 26 chemicals, including four concentrations of each of the four basic taste stimuli, a series of other sugars, salts, and acids, monosodium glutamate, and orange juice. 3. Neurons responsive to taste stimulation could be found in a 76-mm3 region of the amygdala, centered 9.1 mm lateral to the midline, 14.9 mm anterior to the interaural line, and 25.7 mm below the surface of the dura. They composed 7.2% (35/484) of the cells tested for gustatory sensitivity in the amygdala. 4. The mean spontaneous activity of taste cells was 8.2 +/- 2.3 (SE) spikes per second. This rather high level provided an opportunity for reductions from spontaneous rate that was used regularly in the amygdala. When these negative response rates were included, the mean breadth-of-tuning coefficient of this sample of taste cells was 0.82. There was no strong evidence for gustatory neuron types, nor were functionally similar cells located together in a chemotopic arrangement. 5. Responses across 1.5 log units of stimulus concentration were nearly flat, with increasing excitation in some neurons largely offset by increasing inhibition in others. Taking the absolute value of the evoked activity, concentration-response functions rose monotonically to all basic stimuli except HCl, but were not sufficiently steep to account for human psychophysical data. The neural response to HCl did not rise with stimulus concentration within the range used. 6. Neural patterns representing the taste qualities of the basic stimuli were less sharply separated in the amygdala than at lower-order gustatory relays. Glucose elicited activity patterns that were most distinct from those of the nonsweet chemicals; those associated with NaCl were next most distinct. There was no clear separation between the patterns generated by chemicals that humans describe as sour and bitter. Monosodium glutamate evoked responses that did not correlate well with those of any basic stimulus, implying that its quality cannot be subsumed under the four basic tastes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350124 TI - Converging influences from visual, auditory, and somatosensory cortices onto output neurons of the superior colliculus. AB - 1. Physiological methods were used to examine the pattern of inputs from different sensory cortices onto individual superior colliculus neurons. 2. Visual, auditory, and somatosensory influences from anterior ectosylvian sulcus (AES) and visual influences from lateral suprasylvian (LS) cortex were found to converge onto individual multisensory neurons in the cat superior colliculus. An excellent topographic relationship was found between the different sensory cortices and their target neurons in the superior colliculus. 3. Corticotectal inputs were derived solely from unimodal neurons. Multisensory neurons in AES and LS were not antidromically activated from the superior colliculus. 4. Orthodromic and antidromic latencies were consistent with monosynaptic corticotectal inputs arising from LS and the three subdivisions of AES (SIV, Field AES, and AEV). 5. Superior colliculus neurons that received convergent cortical inputs formed a principal component of the tecto-reticulospinal tract. Thus there appears to be extensive cortical control over the output neurons through which the superior colliculus mediates attentive and orientation behaviors. 6. Two other multisensory circuits were identified. A population of multisensory superior colliculus neurons was found, which neither received convergent cortical input nor projected into the tecto-reticulo-spinal tract. In addition, multisensory neurons in AES and LS proved to be independent of the superior colliculus (i.e., they were not corticotectal). While it is likely that these three distinct multisensory neural circuits have different functional roles, their constituent neurons appear to integrate their various sensory inputs in much the same way. PMID- 8350126 TI - Electrophysiological characterization of different types of neurons recorded in vivo in the motor cortex of the cat. I. Patterns of firing activity and synaptic responses. AB - 1. Patterns of firing activity and characteristics of antidromic and synaptic responses to stimulation of the pyramidal tract at peduncular level [peduncular pyramidal tract (PP)] and the ventrolateral thalamic nucleus (VL) were studied in neurons of area 4 gamma of the motor cortex of awake, chronic cats using intracellular microelectrode techniques. The results offer a new functional classification of neocortical neurons based on electrophysiological properties of the 640 recorded cells. 2. Four classes of neurons were distinguished: (class i) inactivating bursting (ib) neurons (n = 60) including fast antidromic response PP (fPP) (n = 0), slow antidromic response PP (sPP) (n = 11), and no antidromic response PP cells (nPP) (n = 49); (class ii) noninactivating bursting (nib) neurons (n = 79), including fPP (n = 23), sPP (n = 0), and nPP cells (n = 56); (class iii) fast-spiking (fsp) neurons (n = 56), including fPP (n = 0), sPP (n = 0), and nPP cells (n = 56); and (class iv) regular-spiking (rsp) neurons (n = 445), including fPP (n = 96), sPP (n = 38), and nPP cells (n = 311). (Neurons in each classification were further separated by their antidromic responses to PP stimulation: fast PP (fPP) slow PP (sPP), or nPP cells, the latter not responding antidromically to electrical stimulation of the peduncle.) 3. Recurrent monosynaptic excitatory postsynaptic potentials (EPSPs) followed antidromic spikes elicited by PP stimulation in most (96%) fPP but much fewer (24%) sPP cells. In fPP cells, it was possible to separate the PP EPSPs into two monosynaptic EPSP components that were generated by other fPP and sPP cells, respectively. VL stimulation evoked monosynaptic EPSPs in 100% of fPP cells (vs. 63% of sPP cells) and antidromic action potentials in 16% of fPP cells (vs. 12% of sPP cells). 4. Firing activity consisted of single spike discharges in most PP cells; however, noninactivating bursting was observed in 19% of fPP cells, and inactivating bursting was observed in 23% of sPP cells (see below). In 18% of ib and 11% of nib/nPP neurons, VL stimulation elicited antidromic action potentials. Other bursting neurons proved to be PP cells with characteristic differences in axonal conduction velocity (see above). All PP cells among the nib cells were fPP, and all PP cells among the ib cells were sPP cells. All fsp neurons were found to be nPP cells, and none could be activated antidromically by VL stimulation. Thus the fsp pattern of discharge distinguished a unique class of nPP cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350128 TI - The relationship of monkey frontal eye field activity to saccade dynamics. AB - 1. In this study, we compared the temporal waveforms of the activity of monkey frontal eye field movement neurons with the dynamics of saccadic eye movements. 2. Movement neurons in the frontal eye field were selected according to previously published criteria. They had little or no response to visual stimuli in a fixation task, and equivalent activity before visually guided and memory guided saccades. We studied corticotectal neurons and corticopontine neurons identified by antidromic excitation, as well as neurons whose projections were not identified. 3. These neurons had a peak activation at a mean of 13 ms before the saccade began. However, rather than falling off rapidly as the saccade ended, most neurons continued to fire after the saccade, returning to baseline at a mean of 93 ms after the end of the saccade. 4. We measured the decrement in activity for these neurons during the saccade. Although a few neurons showed decrements of > 60% of their peak activity level, the average activity dropped only 16.9%, with some neurons actually showing a rise in activity during the saccade. If we ignored the latency between peak in activity and saccade start and measured the fall in activity for a period equal to one saccade duration after the peak, the average drop in activity was still only 34.9%. Thus the activity of these neurons did not appear to be closely related to dynamic motor error, which falls from its maximum value to zero over the time course of a saccade. 5. These results suggest that a focus of movement activity within the topographic map in the frontal eye field specifies the amplitude and direction for an impending saccade, whereas the peak of movement activity signals the time to initiate a saccade. 6. Unlike the superior colliculus, the activity of frontal eye field movement neurons does not appear to be related to dynamic events that occur during the saccade, such as motor error. PMID- 8350127 TI - Electrophysiological characterization of different types of neurons recorded in vivo in the motor cortex of the cat. II. Membrane parameters, action potentials, current-induced voltage responses and electrotonic structures. AB - 1. Electrical properties of four functional classes [inactivating bursting (ib), noninactivating bursting (nib), fast spiking (fsp), and regular spiking (rsp)] of neurons in the motor cortex of conscious cats were studied with the use of intracellular voltage recording and single-electrode voltage-clamp (SEVC) techniques. Evaluations were made of action potentials and afterpotentials, current-voltage (I-V) relationships, and passive cable properties. Values of membrane potential (Vm), input resistance (RN), membrane time constant (T0), and firing threshold (T50) were also measured. The data were used to extend the electrophysiological classifications of neurons described in the companion paper. 2. Average values of Vm (from -63 to -66 mV), action-potential amplitudes (from 72 to 77 mV), and firing threshold (-54 mV) were not statistically different in different types of neurons. However, the magnitude of intracellularly injected depolarizing current required to induce spike discharge at 50% probability varied significantly (from 0.6 to 1.1 nA) among cell types. The mean RN and T0 measured at Vm varied between 8.3 and 19.8 M omega, and 7.2 and 15.1 ms, respectively, in the cell classes. 3. Action potentials were overshooting. Their mean duration at half amplitude varied from 0.25 to 0.73 ms among different cell types. Three types of action-potential configurations were distinguished. Type I action potentials found in nib and rsp neurons were relatively fast and had a depolarizing afterpotential (DAP) as well as fast and slow after hyperpolarizations (fAHPs, sAHPs). Type II action potentials found in ib and rsp cells had relatively slow rise and decay phases, DAPs, and sAHPs. Their fAHPs were small or absent. Type III action potentials were found exclusively in fsp cells, had very short durations, prominent fAHPs, but no sAHPs. 4. Steady-state I V relationships were determined by measuring voltage responses to 0.2- to 1.0-nA hyperpolarizing, rectangular current pulses at different membrane potentials. Both RN and T0 exhibited nonlinear behavior over wide ranges of membrane potential; however, between -65 and -75 mV, the I-V relationships varied little, and they appeared constant in most cells. The steady-state values of RN increased with decreasing, and decreased with increasing the membrane potential in all but fsp cells. The I-V relationships were virtually linear in fsp neurons. 5. Transient I-V relationships were studied by measuring voltage responses to depolarizing and hyperpolarizing, rectangular current pulses of increasing amplitude from a preset membrane potential of -70 mV.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350129 TI - Nociceptive responses in the neostriatum and globus pallidus of the anesthetized rat. AB - 1. Extracellular recordings were made from neurons in the neostriatum (caudate nucleus-putamen, CPu) and globus pallidus (GP) of anesthetized rats. Few cells (3%) were classified as low-threshold-mechanoreceptive (LTM) neurons. The majority (97%) of somatosensory CPu and GP neurons responded differentially or exclusively to noxious mechanical stimulation of the skin. Nociceptive neurons were classified into the following three groups on the basis of their response properties to noxious mechanical stimulation: wide-dynamic-range (WDR) neurons (21%); nociceptive-specific (NS) neurons (67%); and inhibited (INH) neurons (13%). 2. No differences in the response properties or in the proportions of WDR, NS, and INH neurons were found in the CPu compared with the GP. Nociceptive neurons were located most often along the CPu-GP border. Additionally, neurons of similar functional classification were often clustered within 200-400 microns of each other along a single microelectrode track. 3. The receptive fields of nociceptive CPu and GP neurons were often large and bilateral; some receptive fields encompassed the entire body. The trigeminal region, especially the perioral area, was included in the receptive fields of nociceptive neurons more often (62 of 63 cells) than any other part of the body. However, no preference for any particular division of the trigeminal nerve was observed in the receptive fields. Some neurons had receptive fields that were discontinuous. 4. Noxious pinching of the skin significantly increased the spontaneous neuronal discharge of WDR and NS neurons by an average of 482 and 221%, respectively. There were no significant differences between the discharge adaptation rates of WDR and NS neurons. Afterdischarge activity was observed in some WDR and NS neurons. INH neurons decreased their resting activity levels by an average of 43% after a noxious pinch. 5. The von Frey stimulus threshold of WDR neurons (11.0 g/mm2) was significantly lower than that of NS neurons (33.6 g/mm2) and INH neurons (32.6 g/mm2). Mean stimulus thresholds of WDR, NS, and INH neurons determined by using calibrated forceps were 1.6, 4.8, and 2.2 g/mm2, respectively. 6. Individual stimulus-response functions of nociceptive neurons were best fit by a negatively accelerating (logarithmic) curves. However, WDR neurons had significantly steeper slopes than NS neurons. 7. The results demonstrate that a large proportion of somatosensory neurons within the neostriatum and globus pallidus (especially along the CPu-GP border) receive nociceptive information. These data are discussed in relation to several putative afferent nociceptive pathways projecting to the CPu and GP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350130 TI - Dynamics of reflex cocontraction in hermit crab abdomen: experiments and a systems model. AB - 1. Both stretch and release of the ventral superficial muscles (VSM) in the abdomen of the hermit crab, Pagurus pollicarus, activate the VSM motoneurons in the intact animal and in the isolated abdomen. 2. This reflex was studied by recording intracellularly from muscle fibers innervated by single motoneurons during stretch and release of the VSM. The three motoneurons of the right fourth segment respond to both stretch and release with a phasic burst lasting approximately 250 ms. The burst in the two tonic motoneurons has two components, a short burst lasting 10-20 ms, with a latency from the beginning of stretch of 60-90 ms, and a longer burst of variable length, with a latency of 120 ms. Ramp stretches of different amplitudes and velocities were used to show that the first component is proportional to the absolute value of the second derivative of force and the second component to the absolute value of the first derivative of force. 3. Stretch and release of the VSM also simultaneously evoke phasic bursts in the motoneurons of the dorsal superficial muscles and the VSM circular muscles (functional antagonists of the longitudinal VSM), as well as in contralateral homologues of the same segment and in ipsilateral homologues of the next anterior segment. The effect of this coactivation is to stiffen the abdomen in response to perturbations in any direction. 4. Stretch or release of phasic mechanoreceptors in the VSM evokes this reflex. Isometric electrical stimulation of the isolated muscle also activates them, showing that they are transducing changes in force and suggesting that they operate to increase muscle stiffness by positive feedback. 5. A mathematical systems model of this reflex, composed of two parallel pathways activating the motoneurons, was constructed. The first pathway produces a signal proportional to the absolute value of the second derivative of force, the second pathway a signal proportional to the first derivative of force. The sum of the signals from the two pathways is filtered by an adaptation process, which is followed by a low-pass filter representing muscle activation kinetics. The muscle activation signal is then fed back to multiple muscle force. 6. Simulations using this model generate the phasic bursts to stretch and release as well as reproducing the frequency dependence of this reflex. The predominant action of this reflex is to enhance muscle stiffness. PMID- 8350131 TI - The representation of stimulus familiarity in anterior inferior temporal cortex. AB - 1. The inferior temporal (IT) cortex plays an important role in both short- and long-term memory for visual patterns. Most previous studies of IT neurons have tested their responses in recency memory tasks, which require that the memory lasts only the length of a single behavioral trial, which may be < 1 s. To determine the role of IT neurons in longer lasting memories, we measured their responses to initially novel stimuli as the stimuli gradually became familiar to the animal. 2. Two rhesus monkeys were trained on a delayed matching to sample (DMS) task with several intervening stimuli between the sample and the final matching stimulus on each trial. The purpose of the task was to ensure that the animal attended to the stimuli and held them in memory, at least temporarily. Unlike in several previous studies, the focus was not on within-trial effects but rather on the incidental memories that built up across trials as the stimuli became familiar. Each cell was tested with a set of 20 novel stimuli (digitized pictures of objects) that the monkey had not seen before. These stimuli were used in a fixed order over the course of an hour-long recording session, and the number of intervening trials between repetitions of a given sample stimulus was varied. 3. The responses of about one-third of the cells recorded in anterior ventral IT cortex declined systematically as the novel stimuli became familiar. After six to eight repetitions, responses reached a plateau that was approximately 40% of the peak response. Virtually all of these cells also showed selectivity for particular visual stimuli and thus were not "novelty detectors" in the sense of cells that respond to any novel stimulus. Rather, the responses of these cells were a joint function of familiarity and specific object features such as shape and color. A few cells showed increasing responses with repetition over the recording session, but these changes were accompanied by changes in baseline firing rate, suggesting that they were caused by nonspecific effects. 4. The decrement in response with familiarity was stimulus specific and bridged > 150 presentations of other stimuli, the maximum tested. For some cells the maximum decrement in response occurred for those stimuli that initially elicited the largest response. There was no significant change in response to stimuli that were already familiar. 5. The same cells that showed familiarity effects also showed reduced responses to the matching stimuli at the end of each trial, compared with the responses to the samples.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350132 TI - Encoding of head acceleration in vestibular neurons. I. Spatiotemporal response properties to linear acceleration. AB - 1. Extracellular recordings were made in and around the medial vestibular nuclei in decerebrated rats. Neurons were functionally identified according to their semicircular canal input on the basis of their responses to angular head rotations around the yaw, pitch, and roll head axes. Those cells responding to angular acceleration were classified as either horizontal semicircular canal related (HC) or vertical semicircular canal-related (VC) neurons. The HC neurons were further characterized as either type I or type II, depending on the direction of rotation producing excitation. Cells that lacked a response to angular head acceleration, but exhibited sensitivity to a change in head position, were classified as purely otolith organ-related (OTO) neurons. All vestibular neurons were then tested for their response to sinusoidal linear translation in the horizontal head plane. 2. Convergence of macular and canal inputs onto central vestibular nuclei neurons occurred in 73% of the type I HC, 79% of the type II HC, and 86% of the VC neurons. Out of the 223 neurons identified as receiving macular input, 94 neurons were further studied, and their spatiotemporal response properties to sinusoidal stimulation with pure linear acceleration were quantified. Data were obtained from 33 type I HC, 22 type II HC, 22 VC, and 17 OTO neurons. 3. For each neuron the angle of the translational stimulus vector was varied by 15, 30, or 45 degrees increments in the horizontal head plane. In all tested neurons, a direction of maximum sensitivity was identified. An interesting difference among neurons was their response to translation along the direction perpendicular to that that produced the maximum response ("null" direction). For the majority of neurons tested, it was possible to evoke a nonzero response during stimulation along the null direction always had response phases that varied as a function of stimulus direction. 4. These spatiotemporal response properties were quantified in two independent ways. First, the data were evaluated on the basis of the traditional one-dimensional principle governed by the "cosine gain rule" and constant response phase at different stimulus orientations. Second, the response gain and phase values that were empirically determined for each orientation of the applied linear stimulus vector were fitted on the basis of a newly developed formalism that treats neuronal responses as exhibiting two-dimensional spatial sensitivity. Thus two response vectors were determined for each neuron on the basis of its response gain and phase at different stimulus directions in the horizontal head plane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350133 TI - Relative contribution of rod and cone inputs to bipolar cells and ganglion cells in the tiger salamander retina. AB - 1. The relative contribution of rod and cone inputs to bipolar and ganglion cells were studied by comparing the response-irradiance relations, spectral sensitivities, and response waveforms of these neurons recorded from the isolated, flat-mounted tiger salamander retina under dark-adapted conditions. 2. Bipolar cells could be differentiated both on the basis of the polarity of the light response and on their relative rod/cone input. Thus some depolarizing bipolar cells appeared more strongly influenced by rod input (DBCR), whereas others were more influenced by cone input (DBCC). Similarly, hyperpolarizing bipolar cells could be divided into those that received rod-dominant input (HBCR) or cone-dominant input (HBCC). 3. The light onset response of sustained-ON ganglion cells reflected both rod-dominant input from DBCRs and cone-dominant input from DBCCs. 4. OFF ganglion cells displayed both a rod-dominant sustained light offset response and a cone-dominant transient light offset response, suggesting input from both HBCRs and HBCCs. 5. In ON-OFF ganglion cells, the light onset response was strongly rod dominated and was presumably mediated by DBCRs, whereas the light offset response displayed both rod and cone influence, suggesting input from HBCRs and HBCCs. The contribution of cones to the light onset response of ON-OFF ganglion cells was only observed in the presence of a rod-adapting background light. 6. A suppression of the light offset responses of OFF and ON-OFF ganglion cells was observed, which was dependent both on the wavelength and irradiance of the light stimulus. 7. These results indicate that the photoreceptor inputs to bipolar cells in the tiger salamander retina are segregated such that they form separate rod-dominant and cone-dominant pathways. Thus the response properties of the different types of ganglion cells are influenced not only by the excitatory and inhibitory inputs they receive from the bipolar and amacrine cells but also whether these inputs are provided through rod dominant or cone-dominant pathways. The functional implications of these findings are discussed. PMID- 8350134 TI - Reduced control of motor output in a human hand muscle of elderly subjects during submaximal contractions. AB - 1. The effect of age on the motor output of the first dorsal interosseous muscle of 22 (6 female, 16 male) human subjects was investigated. The purpose of the study was to determine the effect of age on the control of muscle force and the associated changes in the discharge behavior and mechanical properties of single motor units. 2. Each subject performed three tasks requiring isometric abduction of the left index finger: a maximum voluntary contraction (MVC), a constant-force task, and a threshold task. The ability to control force was assessed during the constant-force task by quantifying the variation in isometric force about four submaximal target forces (5, 20, 35, and 50% MVC). The threshold task involved sustaining the discharge of the isolated motor unit at a low, steady rate for approximately 3 min. 3. The discharge behavior and the mechanical properties of single motor units were determined during the threshold task by measuring the interimpulse intervals and the peak amplitude and time to peak of the spike triggered average force. 4. The data indicated that age had an effect on the variation of force about submaximal target forces (range: 5-50% MVC), and that these force variations, when calculated relative to the target force, were greater at lower force levels in the elderly subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350135 TI - Small-caliber afferent inputs produce a heterosynaptic facilitation of the synaptic responses evoked by primary afferent A-fibers in the neonatal rat spinal cord in vitro. AB - 1. The effect of brief primary afferent inputs on the amplitude and duration of the synaptic potentials evoked in ventral horn (VH) neurons by the activation of other unconditioned primary afferents was studied by current-clamp intracellular recording in the neonatal rat hemisected spinal cord in vitro. Low-frequency (1 Hz) trains of stimulation were applied to a lumbar dorsal root (Conditioning root) for 20-30 s. Test excitatory synaptic potentials (EPSPs) were evoked by single electrical shocks applied to an adjacent Test dorsal root. 2. Test and Conditioning inputs were generated at stimulation strengths sufficient to activate A beta-, A delta- and C-afferent fibers successively. At A delta- and C fiber strength the EPSPs lasted for 4-6 s, and, during the repetitive Conditioning inputs, these summated to produce a progressively incrementing cumulative depolarization that slowly decayed back to the control Vm over tens of seconds. 3. Dorsal root conditioning produced heterosynaptic facilitation, defined as an enhancement of Test EPSPs above their DC matched controls, in 7 out of 20 neurons. To facilitate the unconditioned afferent input, the intensity of conditioning stimulation had to exceed the threshold for the activation of thin myelinated (A delta) afferents: conditioning at A beta-fiber strength had no effect, whereas A delta- and C-fiber strength conditioning were equally effective. 4. Heterosynaptic facilitation of only A beta- or A delta-fiber-evoked Test EPSPs was observed, no enhancement of C-fiber strength Test EPSPs could be demonstrated. The facilitation manifested as increases in the EPSP peak amplitude, area or the number of action potentials evoked. 5. Conditioning trials that produced heterosynaptic facilitation generated cumulative depolarizations larger than those produced by ineffective conditioning trials (9.1 +/- 3.1 vs. 3.3 +/- 0.5 mV after 20 s conditioning at resting Vm, mean +/- SE, n = 6 and 13, respectively; P < 0.05). The slope of the Vm trajectory during the summation of the conditioning EPSPs was higher in trials resulting in heterosynaptic facilitation, at 0.31 +/- 0.10 mV/s in neurons with heterosynaptic facilitation and 0.06 +/- 0.02 mV/s in cells without heterosynaptic facilitation (P < 0.05). 5. Four of the 20 VH neurons in our sample responded to A delta/C-fiber conditioning with action-potential windup: all 4 also displayed heterosynaptic facilitation. 6. Heterosynaptic facilitation decayed after the completion of the conditioning stimulus with a time course that was parallel to but not superimposable on that of the slow Vm depolarization evoked by the conditioning.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350137 TI - Inhibition in ON-OFF directionally selective ganglion cells of the rabbit retina. AB - 1. We have investigated the inhibitory mechanisms modulating the extracellularly recorded responses of ON-OFF directionally selective (DS) ganglion cells of the rabbit retina. Our investigations used both moving spots and apparent motion. The latter was produced by both prolonged light steps, which simulate movement of an edge, and light flashes, which simulate movement of a spot or slit. 2. Within the excitatory receptive-field center of DS ganglion cells, apparent motion with prolonged light steps elicits null-direction inhibition whose strength rises to 90% of maximum in 160 +/- 110 ms (7 cells) and then decays slowly, remaining above baseline longer than 2,000 ms for short interslit distances. 3. Prolonged light steps are generally effective for inhibiting any given excitatory receptive field locus from an ovate-shaped area that extends asymmetrically in the direction that would be previously traversed by null-direction moving objects. This inhibitory area is typically larger than one-half the size of the receptive field center. The strength of the inhibition is greater at short than long distances within this area. 4. The rise and fall times of the null-direction inhibition elicited by apparent motion using prolonged light steps are somewhat faster at large than short interslit distances. 5. Short light flashes (at sufficiently long interslit delays) elicit inhibition not only from the same asymmetric, ovate-shaped inhibitory field as long steps of light, but also from loci completely surrounding the second slit. This implies that the asymmetric, null-direction-specific inhibition is due to a temporally sustained mechanism. The symmetric inhibition elicited by short flashes may be due to the presence of the antagonistic surround mechanism within the receptive-field center. The apparent absence of this surround inhibition for preferred-direction apparent motion during prolonged light steps may be due to masking by facilitation that is strongly evoked by long steps, but not flashes of light (see accompanying paper). 6. The relatively slow rise time and sustained time course of the inhibition elicited by null-direction apparent motion within the excitatory receptive field center appears to distinguish it from the inhibition elicited by stimulation within the receptive field surround, which has a much faster rise time and more transient time course. However, the sustained, null-direction inhibitory mechanism that can be elicited by prolonged light steps within the excitatory receptive field center extends into the surround on the side of the receptive field center previously traversed during null-direction motion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350136 TI - Multiple potassium conductances and their role in action potential repolarization and repetitive firing behavior of neonatal rat hypoglossal motoneurons. AB - 1. The role of multiple potassium conductances in action potential repolarization and repetitive firing behavior of hypoglossal motoneurons was investigated using intracellular recording techniques in a brain stem slice preparation of the neonatal rat (0-15 days old). 2. The action potential was followed by two distinct afterhyperpolarizations (AHPs). The early one was of short duration and is termed the fAHP; the later AHP was of longer duration and is termed the mAHP. The amplitudes of both AHPs were enhanced by membrane potential depolarization (further from EK). In addition, their amplitudes were reduced by high extracellular K+ concentration, suggesting that activation of potassium conductances underlies both phases of the AHP. 3. Prolongation of the action potential and blockade of the fAHP were observed after application of 1) tetraethylammonium (TEA) (1-10 mM) and 2) 4-aminopyridine (4-AP) (0.1-0.5 mM). Calcium channel blockers had little or no effect on the fAHP or action potential duration. 4. The size of the mAHP was diminished by 1) manganese, 2) lowering external Ca2+, 3) apamin, and 4) intracellular injection of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) suggesting that influx of calcium activates the potassium conductance that underlies the mAHP. 5. The mAHP was unaffected by nifedipine (20 microM), but was strongly reduced by focal application of omega-conotoxin GVIA, suggesting that N-type calcium channels represent the major calcium influx pathway for activation of the calcium dependent K+ conductance underlying the mAHP. 6. Repetitive firing properties were investigated by injecting long-duration depolarizing current pulses. Steady state firing rose linearly with injected current amplitude. The slope of the firing frequency-current (f-I) relationship averaged approximately 30 Hz/nA in control conditions. Blockade of the conductance underlying the mAHP caused a marked increase in the minimal repetitive firing frequency and in the slope of the f-I plot, indicating a prominent role for the conductance underlying the mAHP in controlling repetitive firing behavior. 7. We conclude that action potential repolarization and AHPs are due to activation of pharmacologically distinct potassium conductances. Whereas repolarization of the action potential and the fAHP involves primarily a voltage-dependent, calcium-independent potassium conductance that is TEA- and 4-AP-sensitive, the mAHP requires the influx of extracellular calcium and is apamin sensitive. Activation of the calcium activated potassium conductance greatly influences the normal repetitive firing of neonatal hypoglossal motoneurons. PMID- 8350138 TI - Facilitation in ON-OFF directionally selective ganglion cells of the rabbit retina. AB - 1. We have investigated the facilitation of extracellularly recorded responses of ON-OFF directionally selective (DS) ganglion cells of the rabbit retina to two slit preferred-direction apparent motion produced by both prolonged light steps, which simulate movement of an edge past two apertures, and light flashes, which simulate movement of a spot or slit. 2. Within the excitatory receptive-field center of DS ganglion cells, apparent motion with prolonged light steps elicits preferred-direction facilitation whose rise time (220 +/- 150 ms, average rise to 90% of maximum for 6 cells) is typically longer than the rise time of the excitatory response elicited by each slit. The decay time to baseline of facilitation during prolonged light steps is generally longer than 500 ms and hence greatly exceeds the typical duration of the excitatory response elicited by the slits. 3. Prolonged light steps are generally effective for facilitating any given excitatory receptive-field locus from a roughly ovoid area that typically extends on the order of 100-200 microns in the preferred direction, which is less than one-half the size of the excitatory receptive-field center. Within 100 microns, facilitation can occur for motion diagonal to the preferred-null axis as long as the projection of the motion on the preferred-null axis points in the preferred direction. 4. The time course of preferred-direction facilitation between two slits does not appear to have a strong systematical dependence on the interslit distance over the range in which facilitation is effective. 5. Short light flashes are ineffective for eliciting facilitation and, at sufficiently long interslit delays, elicit inhibition all around the test slit. This inhibition may be due to the antagonistic surround mechanism within the receptive field center, which is effectively elicited by short-duration stimuli. 6. The effect of preferred-direction facilitation is addition-like, rather than multiplication-like. That is, the facilitatory effect of the first slit appears as the addition of a fixed value to the response-versus-contrast curve of the second slit, rather than a multiplication of the curve by a constant factor. The functional relationship between strength of facilitation and contrast of the first slit is sigmoidal, however, and thus nonlinear. 7. Experiments with long light steps show that the interaction between excitation and preferred-direction facilitation is largely segregated between the ON and OFF pathways.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350139 TI - CA3 neuron excitation and epileptiform discharge are sensitive to osmolality. AB - 1. The clinical signs of rapidly developing overhydration commonly include generalized tonic-clonic seizure, which can be combatted by raising plasma osmolality. How cortical neurons respond to osmotic imbalance has been addressed only recently. In the CA3 cell region of hippocampal slices, lowered osmolality ( 40 mOsm) rapidly swelled cells, increasing field potential amplitude over a period of 8 min and thereby elevating field effects and associated neuronal synchronization. 2. Over a longer time course (10-30 min), spontaneous excitatory postsynaptic potential (EPSP) amplitude gradually increased in 7 of 10 CA3 neurons recorded intracellularly. In nine additional CA3 cells, hyposmolality gradually induced combinations of action potential discharge, endogenous bursting, and increased synchronized synaptic input. All of these effects reversed in normosmotic ACSF. 3. Hyperosmotic artificial cerebrospinal fluid (ACSF) using mannitol reduced field potentials and dramatically lowered CA3 excitability by reducing spontaneous EPSP amplitude and associated bursting. Again, the gradual onset (10-30 min) of changes in spontaneous EPSP amplitude appeared independent of field potential changes, which were already maximal by 8 min. 4. Cutting mossy fibers did not affect the excitability changes induced by osmotic stress noted above. The EPSP/inhibitory postsynaptic potential (IPSP) sequence evoked from mossy fibers or stratum oriens was unaltered by osmotic change and so did not represent osmosensitive afferent input to CA3 neurons. Furthermore, as measured at the soma, resting membrane potential, cell input resistance, and the action potential threshold were unchanged in all cells. It followed that, because the CA3 neurons themselves were not responsive, a recurrent excitatory pathway could not represent the osmosensitive input.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350140 TI - Position-specific adaptation in complex cell receptive fields of the cat striate cortex. AB - 1. Responses of complex cells in cat striate cortex were studied with flashed light slit stimuli. The responses to slits flashed in different positions in the receptive field were assessed quantitatively before and after periods of prolonged stimulation of one small region of the receptive field. This type of prolonged stimulation resulted in reduced responsivity over a limited zone within the complex cell receptive field. 2. The adaptation-induced responsivity decrement was generally observed in both the ON and OFF response profiles but could also be restricted to one or the other. In general, the magnitude of the response decrements was greatest in the ON response profiles. The adaptation induced response decrement did not necessarily spread throughout the receptive field but was restricted to a small region surrounding the adapted receptive field position (RFP). Adaptation spread equally widely across the ON and OFF response profiles despite the smaller adaptation effects in the OFF profile. 3. The adaptation effects from repeated stimulation at a single RFP did not spread symmetrically across the receptive field, and a given cell's preferred direction of motion indicated the direction of the asymmetric spread of the adaptation. RFPs that would be stimulated by a light slit originating at the point of adaptation and moving in the preferred direction (preferred side) showed greater adaptation-induced response decrements than did RFPs that would be stimulated by a light slit moving in the opposite direction from the point of adaptation (nonpreferred side). There was significant enhancement of responses at some RFPs on the non-preferred side of the point of adaptation. This asymmetric spread of adaptation could be caused by adaptation of inhibitory connections that contribute to complex cell direction selectivity. 4. The asymmetry of adaptation was significantly different for the ON and OFF response profiles. The asymmetric spread of adaptation for the ON response profile was similar to that observed previously in simple cells with greater decrements in the preferred direction side of the point of adaptation. However, the OFF response profiles showed less directional asymmetry in the spread of adaptation and showed greater decrements at RFPs in the nonpreferred direction side of the point of adaptation. 5. The similarity between the spread of adaptation in simple and complex cells suggests that the adaptation in these cells is occurring through a common mechanism. The directional asymmetry of the spread of adaptation is likely due to a local postsynaptic mechanism of adaptation rather than presynaptic transmitter depletion. PMID- 8350141 TI - Activity of medullary reticulospinal neurons during fictive locomotion. AB - 1. The pattern of discharge of medullary reticulospinal neurons, identified by antidromic stimulation applied at the L1-L2 segment of the spinal cord, was studied during fictive locomotion, occurring spontaneously, or evoked by stimulation of the mesencephalic locomotor region in high-decerebrate, paralyzed cats. Unitary recordings were made in the medial reticular formation (P5.0-14.0 mm; L0.5-2.0 mm), and the fictive locomotor pattern was monitored by recording the electroneurogram (ENG) of representative flexor and extensor muscle nerves from each of the four limbs. 2. In total, 117 reticulospinal neurons were recorded in 15 cats. Among these, 73.5% (86/117) modified their discharge at the onset of locomotion. These cells were divided into three subpopulations: 34/86 of the cells always maintained a fixed temporal relationship with the activity of one of the recorded nerves (ENG-related = 39.6%); the pattern of discharge of 42/86 cells was related to the locomotor rhythm [(LR-related-48%)] but was not temporally correlated with any of the recorded nerves; and the remaining 10 cells increased their firing frequency at the onset of locomotion but remained tonic (TONIC-11.6%). 3. Of the ENG-related neurons, 64.8% were temporally correlated to extensor nerve activity, whereas the remaining 35.2% were correlated to flexor nerves. These neurons were either related to forelimb (55.9%) or hindlimb (44.1%) nerves lying either ipsilateral (38.2%) or contralateral (61.8%) to the recording site. A few neurons (n = 3; 8.8%) were related to nerve activity of more than one limb. 4. The pattern of discharge of the LR-related neurons, although not correlated to the activity of any one recorded nerve, could be preferentially related to the locomotor rhythm in either the forelimbs (12/23) or hindlimbs (11/23). 5. ENG- and LR-related reticulospinal neurons were intermingled in the medial reticular formation. In both cases, cells related to the forelimbs were located more dorsally than those related to the hindlimbs. It is suggested that both the ENG- and LR-related neurons represent a single functional population of reticulospinal neurons that is part of an intrinsically organized reticulospinal system that functions to coordinate the activity of the skeletal musculature. 6. The present results show that the majority of reticular neurons projecting as far as the lumbar spinal cord are phasically modulated during locomotion, even in the absence of phasic peripheral afferent inputs. Moreover, the complexity of the discharge patterns in paralyzed animals was found to be similar to that observed in the intact cat.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350142 TI - Nonlinear dynamics in a model neuron provide a novel mechanism for transient synaptic inputs to produce long-term alterations of postsynaptic activity. AB - 1. A mathematical model of a bursting molluscan neuron has been found to possess multiple modes of electrical activity, such as periodic beating (tonic firing), periodic bursting (bursts of action potentials separated by quiescent periods), and potentially chaotic bursting, all at a single set of parameters. The multiple modes correspond to multiple stable attractors, whose existence is an emergent property of the nonlinear dynamics of the system. 2. Transient synaptic inputs can switch the activity of the neuron between different modes. These mode transitions, which do not require any changes in the biochemical or biophysical parameters of the neuron, provide an enduring response to a transient input, as well as a mechanism for phasic sensitivity (i.e., temporal specificity). 3. These results provide new insights into the role of nonlinear dynamics in information processing and storage at the level of the single neuron. PMID- 8350143 TI - Responses of neurons in primary visual cortex are modulated by eye position. AB - 1. We tested the effects of eye position on the visual excitability of 88 neurons in the primary visual cortex of awake cats trained in oculomotor tasks. For most cells, we examined responses evoked by retinotopically identical stimuli for centered gaze, 8 degrees to the left of center, and 8 degrees to the right of center. 2. An effect of eye position was observed for 40% of the cells. For 13%, responsiveness varied by a factor of 2 or more. Most commonly, response was maximal with gaze shifted to one side, minimal when shifted to the opposite side, and intermediate for centered fixation. The exceptions were four cells for which excitability varied symmetrically with fixations to either side of center. 3. Variability in excitability associated with eye position is a wide-spread phenomenon, having been observed in the lateral geniculate nucleus, V1, and extrastriate cortex. These results are consistent with the belief that such variability is utilized in constructing a head-centered frame of reference from a retinotopic input. PMID- 8350144 TI - Effect of spatial configuration on motion aftereffects. AB - Sensitivity to motion was measured by the percentage of trials on which an observer reported seeing motion of briefly presented high-contrast sinusoidal gratings moving over a range of velocities. The psychometric curve was remeasured following adaptation to a grating moving in one direction for an extended period of time. Adaptation shifted the minimum of the psychometric curve toward the direction of the direction of the adapting stimulus. The shift was smaller when the adapting field was larger than the test. In a second set of experiments we measured the effect of motion adaptation on contrast thresholds for moving gratings of different sizes. Threshold elevation was maximal when adapting and test sizes matched. We present a mechanistic model of the motion aftereffect that consists of independent multiplicative gain controls in motion-sensing mechanisms tuned to different rates of motion. In addition, we discuss a model of size effects in motion adaptation that invokes diffuse inhibitory connections among motion-sensing mechanisms. PMID- 8350145 TI - Signal sampling and propagation through multiple cell layers in the retina: modeling and analysis with multirate filtering. AB - The retina is a multilayered structure. Each layer consists of one or more classes of cell, each at its own density and with its own anatomic and physiologic properties. Signals converge from many cells in one layer onto single cells in another layer, and a signal from a single cell diverges to many cells in the next layer. In this methods paper we develop a general approach to retinal analysis and modeling that incorporates multiple cell classes, their densities, and related anatomic properties. The method is based on multirate filtering, a branch of signal processing in which signals of different sampling rates are manipulated. By drawing a correspondence between cell density and signal sampling rate, we define multirate models that incorporate different cell densities, convergence, divergence, variation in dendritic field shape, cell-to-cell variation in synaptic weights, and other anatomic features. We develop the multirate approach and apply it to the cat cone-->cone bipolar CBb1-->on-beta ganglion cell pathway as an example. We calculate the spatial frequency responses of the CBb1 and on-beta cells based on the cone spatial frequency response and find that the attenuation of high frequencies in the cones prevents aliasing that would otherwise occur in CBb1 and on-beta cells. We compare the calculations with cat psychophysics. We show that the optics of the cat eye are insufficient in themselves for the prevention of aliasing in these cells; additional attenuation by the cone-cone gap junctions and the cone aperture is necessary. By including this postreceptoral filtering, we demonstrate that the highest spatial frequency that can be passed by the retina without aliasing is determined not always only by the densities of cones, bipolar cells, and ganglion cells but also by the synaptic and the dendritic weighting between these cells. PMID- 8350146 TI - Optics of the harbor porpoise eye in water. AB - A two-dimensional ray-tracing model for the harbor porpoise eye is constructed from new measurements, mainly on two enucleated eyes, and from data found in the literature. Model calculations show that the crystalline lens has too much refractive power to focus light on the retina. The cornea has a high refractive index and acts as a diverging lens of considerable refractive power. The cornea corrects the eye to near emmetropia for axial and temporal (caudal) directions of view. The eye is approximately 5-D myopic for nasal (frontal) directions of view. The iris serves a dual role as a stop: the iris determines the shapes of bundles of light that enter the lens and the iris blocks light that leaves the lens anterior to its equator. PMID- 8350147 TI - Loci of achromatic points throughout the life span. AB - Mixtures of monochromatic lights that appear achromatic were measured for 50 normal, trichromatic observers ranging in age from 11 to 78 years. Stimuli were presented to one eye as a 1 degree-diameter, 1-s flash (10-s interstimulus interval) in Maxwellian view. We found the achromatic locus by varying the intensity ratio of each observer's spectral unique blue and unique yellow while maintaining constant overall retinal illuminance. Measurements were made for three levels of retinal illuminance (10, 100, 1000 trolands). Additional verification of the position of the achromatic locus in color space was obtained for 23 subjects with the use of a mixture composed of 600-nm light and its spectral complement. There were no significant changes in the achromatic loci as a function of age. The mean achromatic locus in CIE chromaticity space was x, y = 0.31, 0.31 or u',v' = 0.21, 0.46. These results suggest that partial compensation for age-related changes in visual mechanisms occurs in a way that preserves constancy of the achromatic locus across the life span. PMID- 8350148 TI - Modeling the contrast-sensitivity functions of older adults. AB - To determine whether a parabolic template is a good description of the contrast sensitivity functions (CSF's) exhibited by older adults, the curve-fitting method of Pelli et al. [J. Opt. Soc. Am. A 3(13), P56 (1986)] was applied to contrast sensitivity data from 100 older subjects (ages 53-85 years). Although the method resulted in reasonable fits for most subjects, closer inspection revealed that this technique may be problematic. A significant number of observers had functions that were nonparabolic, and for many subjects the error tended to be concentrated at the peak of the CSF. In addition, in contrast to the study of Pelli et al., the peak contrast sensitivities of the subjects were only weakly related to Pelli-Robson contrast sensitivity and letter acuity. The data were also fitted with an asymmetric function of variable shape. Whereas this function provided a better fit to the nonparabolic CSF's, it resulted in inferior fits to most of the remaining data. These results demonstrate that the spatial CSF's of older adults cannot be described by a single parametric curve such as a parabola or a function of an exponential and that Pelli-Robson contrast sensitivity and letter acuity are not adequate predictors of their peak contrast sensitivities. PMID- 8350149 TI - Phenomenological model for interpreting the clinical significance of the in vitro optical transfer function. AB - We describe a methodology to predict the outcome of clinical tests caused by changes made to the optical elements of the human eye. This formalism, called the expected visual outcome model, is based on in vitro measurements of the optical transfer function and takes into account a simple model of human threshold performance. The clinical tests under consideration are high-contrast visual acuity and contrast sensitivity. Using the expected visual outcome, we describe a useful performance index called the predicted visual acuity graph, which can be measured clinically. The theoretical results are compared with visual function measured in patients with pseudophakic (multifocal and monofocal) implants. PMID- 8350150 TI - Parametric representation of Stiles-Crawford functions: normal variation of peak location and directionality. AB - Evidence suggests that the psychophysically determined Stiles-Crawford effect of the first kind (SCE) reflects waveguide properties of human photoreceptors. The peak of the SCE data set is assumed to reflect the principal alignment tendencies, and the spread (e.g., rho value, the curvature or width at half height) is assumed to reflect the directionality (i.e., interreceptor differences in alignment) of the population of photoreceptors being tested. As such, disruption of the normal SCE can be used and/or has been used (1) to document early natural history of retinal pathology involving the photoreceptors, (2) to provide a firm rationale for therapeutic intervention, and (3) to provide a method for monitoring therapies designed to alter the natural course of retinal disease processes. We report large-sample norms for foveal SCE peak location and spread (horizontal peak location, nasal 0.51 +/- 0.72, horizontal rho value 0.047 +/- 0.013, vertical peak location, superior 0.20 +/- 0.64, vertical rho value 0.053 +/- 0.012), compare these norms with values determined in other laboratories, and discuss the various mathematical forms used for the empirical description of SCE data sets. PMID- 8350151 TI - Heterogeneity in retinal disease and the computational model of the human-rod response. AB - Abnormal rod-receptor activity can be quantitatively assessed in humans by fitting a computational model of the rod's response to the leading edge of the a wave of the electroretinogram. One purpose of the present study was to compare two procedures for fitting the model to the electroretinogram. A computationally simpler method gives comparable results to the more labor-intensive method used previously. This finding holds for both normal observers and patients with retinodegenerative disease that affects the receptors unevenly. A second purpose of the present study was to consider the effects of a heterogeneous disease process on the parameters of the model. a waves from a heterogeneous retina are computer simulated and are fitted with the receptor model. This analysis suggests that the model will overestimate the change in the healthiest rods and will underestimate the percentage of the rods that are significantly affected. PMID- 8350152 TI - Temporal properties of letter identification in retinitis pigmentosa. AB - The effect of stimulus duration on the visual acuity of individuals with retinitis pigmentosa (RP) was assessed by using Sloan letters of 100% contrast and durations ranging from 15 ms to 3.8 s. In addition, contrast thresholds for identifying Sloan letters (0.7 log minimum angle of resolution; 20/100 Snellen equivalent) were measured over the same range of durations in the same subjects with RP. Compared with results from a control group of subjects with normal vision, the subjects with RP showed losses in visual acuity at all stimulus durations, with a slightly though significantly greater reduction in visual acuity at short durations. The letter-contrast thresholds of the subjects with RP were elevated above the normal range to the same degree at all durations. Analysis of the results in the format of letter contrast sensitivity functions indicates that temporal summation for letter identification was normal for these subjects with RP and that their relatively greater acuity loss at short exposure durations was most likely related to their elevated letter contrast thresholds. PMID- 8350153 TI - Fractal analysis of steady-state-flicker visual evoked potentials: feasibility. AB - Electrophysiological models of visual evoked potential recording have assumed that response variability is caused predominantly by random noise added to a true steady signal. Since neuronal geometry has a fractal structure, neural activity may demonstrate deterministic nonlinear dynamics, i.e., chaos. We recorded several-minute time-series traces of the visual evoked potential magnitude in response to full-field flicker from three glaucoma patients and one normal subject. When plotted in phase space, the steady-state response derived from a lock-in amplifier shows an apparent so-called strange attractor (extended nonrepeating loops) rather than the pattern expected from a signal-plus-noise model (a fuzzy dot). The fractal dimension of this attractor may be a more sensitive indicator of early optic-nerve damage than are visual evoked potential latency or amplitude measures. PMID- 8350154 TI - Axial eye-length measurement by wavelength-shift interferometry. AB - A simplified noncontact measuring technique for axial eye length was developed. According to this method, the wavelength shift of a single-mode laser-diode beam that is irradiated onto the eyeball causes a phase shift in the interference fringes of reflections from the retina and the cornea. Then the optical distance between the cornea and the retina is obtained from the phase-shift measurement. High-speed axial eye-length measurements can be performed by using a laser diode on a pulse-modulation drive and signals from the reference light path as an analog-to-digital-conversion trigger. Compared with the technique that uses partially coherent light, this technique is inferior in terms of measurement accuracy but superior in its wide, measurable range of 16-32 mm. The results of measurements of 21 adults showed that 2 standard deviations of measurement was 2 sigma = +/- 0.11 mm. PMID- 8350155 TI - Effects of aging in retinal image quality. AB - The retinal image quality characterized by the modulation-transfer function of the eye was measured for two groups of subjects aged in the late twenties and mid sixties, respectively. In both groups, we obtained modulation transfer functions by using a double-pass method under the same experimental conditions: 4-mm artificial pupil, paralyzed accommodation, and objective control of the refractive state and centering. Results showed lower values of modulation in the retinal image for older subjects compared with the younger subjects. The modulation transfer function ratio is similar to that previously found for contrast-sensitivity measurements with subjects in the same age groups. These results suggest that a significant fraction of the loss in spatial vision with age has an optical origin. Apart from the well-known increase in intraocular scattering, there also appears to be an increment in ocular aberration that causes an additional reduction in the contrast of retinal images. PMID- 8350156 TI - Eye-tracking laser Doppler velocimeter stabilized in two dimensions: principle, design, and construction. AB - We developed an eye-tracking laser Doppler velocimeter to minimize eye-movement artifacts in the study of ocular hemodynamics in humans. The instrument compensates for both horizontal and vertical eye motions by using galvanometer mirrors controlled by a dual-Purkinje eye tracker. The performance of the instrument is demonstrated in a preliminary study of retinal arterial blood velocity in a normal subject. The subject's fixation point was adjusted manually to oscillate through a 2.3-deg span at 0.3 Hz. In spite of this motion the pulsatile velocity waveform of the heart cycle could be continuously recorded. Without eye tracking the velocity waveform was lost after the initiation of movement. PMID- 8350157 TI - Clinical microscopy of the cornea utilizing optical sectioning and a high numerical-aperture objective. AB - A doublet contact element was added to a long-working-distance objective to increase the numerical aperture to 0.75 and to maintain the focus during in vivo examination of the eye. Optical sectioning by use of confocal slits permits visualization of weakly scattering structures within the cornea. With photographic film and a 1/60-s exposure time to limit the effect of eye movement, an effective optical section half-thickness of approximately 20 microns was realized. Structures observed in the cornea include epithelial cells (surface, wing, and basal cells), nerve-fiber bundles in the subepithelial region, keratocytes and inflammatory cells in the stroma, and endothelial cells. PMID- 8350159 TI - Hybrid model of Monte Carlo simulation and diffusion theory for light reflectance by turbid media. AB - Light reflectance by semi-infinite turbid media is modeled by a hybrid of Monte Carlo simulation and diffusion theory, which combines the accuracy of Monte Carlo simulation near the source and the speed of diffusion theory distant from the source. For example, when the turbid medium has the following optical properties- absorption coefficient 1 cm-1, scattering coefficient 100 cm-1, anisotropy 0.9, and refractive-index-matched boundary--the hybrid simulation is 7 times faster than the pure Monte Carlo simulation (100,000 photon packets were traced), and the difference between the two simulations is within 2 standard deviations of the Monte Carlo simulation. PMID- 8350158 TI - Method for measuring visual resolution at the retinal level. AB - To measure the intrinsic resolving capacity of the retinal and neural levels of vision, we devised a method that creates two lines with controllable contrast on the retina. The line separation can be varied at will, down to values below those achievable with conventional optical techniques. Implementation of the method with use of a He-Ne laser leads to a procedure that permits analysis of the performance of the human visual apparatus. PMID- 8350160 TI - Pigment tests evaluated by a model of chromatic discrimination. AB - Clinical color-vision tests are evaluated within the framework of a model of chromatic discrimination in terms of cone excitation. The motivation for this study was to derive a method for evaluation of test design, test sensitivity, and observer performance. The discrimination model is based on the assumption that chromatic discrimination is mediated in two independent channels, one for short wavelength cones and one for long- and middle-wavelength cones. Luminance dependent templates are derived for each channel, and they describe chromatic discrimination behavior of the young color-normal observer. The templates incorporate receptor- and opponent-level gain controls. We show how the chromaticities of clinical tests can be calculated in cone-excitation units and how discrimination behavior on the tests can be plotted on the templates. The tests include the Farnsworth-Munsell 100-hue, the Farnsworth Panel D-15, the Farnsworth Panel D-15 desaturated, the American Optical Hardy-Rand-Rittler, the Farnsworth F2 plate, the Standard Pseudoisochromatic Plates, Part II, the Ishihara, and the Minimalist tests. Clinical-test data collected on young color normal observers at different illumination levels show the validity of the techniques. PMID- 8350161 TI - Chromatic and luminance sensitivity in diabetes and glaucoma. AB - The effects of glaucoma and diabetes on the sensitivities of the opponent and achromatic systems were investigated by measuring thresholds along theoretically defined axes in a three-dimensional color space. Thresholds were measured along two equiluminant chromatic axes and one achromatic axis in patients with diabetes or glaucoma and in glaucoma suspects. The results were compared with measures of sensitivities of short- and middle-wavelength-sensitive-cone pathways [S (Stiles pi 1) and M (Stiles pi 4), respectively] and with measures of hue discrimination by use of the Farnsworth-Munsell 100-hue test. The glaucoma suspects and diabetic patients showed preferential S-cone-pathway sensitivity losses. For glaucoma patients, however, these losses were associated with significant decreases in the sensitivity of the L-M opponent system and with decreased sensitivity to achromatic contrast. PMID- 8350162 TI - Longitudinal comparison of temporal-modulation perimetry with white-on-white and blue-on-yellow perimetry in ocular hypertension and early glaucoma. AB - We obtained data over 3 years on temporal-modulation perimetry (TMP), standard automated [white-on-white (W/W)] perimetry, and short-wavelength-sensitive [blue on-yellow (B/Y)] perimetry in ocular hypertensive (OH) patients and patients with early glaucomatous visual-field loss (EG). Evidence of visual-field defects was obtained with the use of both B/Y perimetry and TMP in the majority of OH and EG eyes that demonstrated progression on W/W perimetry as well as in all stable EG eyes. Using the nerve-fiber-bundle pattern to compare testing procedures, we determined that these defects were generally as extensive or more extensive than the concurrent W/W abnormalities. In terms of location over the 3 years of testing, TMP and B/Y defects were reasonably consistent in the EG eyes, somewhat less consistent in the OH eyes demonstrating progression, and both inconsistent and infrequent in the stable OH eyes. The greatest degree of overlap occurred between the location of defects obtained by use of the higher TMP frequencies (8 and 16 Hz) and that of defects obtained by use of B/Y perimetry. Since these two methods are thought to isolate different visual mechanisms subserved by different visual pathways, these results suggest that early glaucomatous visual-field damage as revealed by TMP and B/Y perimetry may not be specific to a single visual pathway. PMID- 8350163 TI - Analysis of Rayleigh match data with psychometric functions. AB - Color matches have been used for a variety of purposes, yet the psychometric properties of color-matching data have not been thoroughly investigated. A method is given for generating psychometric functions for the two ends of the color matching range by use of a perceptual dimension for stimulus magnitude based on ratios of cone quantal catches. The analysis was applied to Rayleigh match data gathered from 250 naive observers with an automated protocol. Slopes of the psychometric functions were significantly shallower for anomalous trichromats than for normal trichromats, consistent with the assumption that stimulus magnitude is based on ratios of cone quantal catches. These results indicate that the tester's criterion for response consistency can strongly affect Rayleigh match widths. The analysis may also be useful for other perceptual tasks, such as contrast matching and spatial alignment. PMID- 8350164 TI - Application of the spatiochromatic visual evoked potential to detection of congenital and acquired color-vision deficiencies. AB - Visual evoked potentials were recorded in response to spatiochromatic stimuli modulated in different directions in cone-activation color space from subjects with congenital and acquired color defects. This technique was effective for detection and classification of both mild and severe forms of congenital deficits. Results suggest that the visual evoked potential is useful for early identification of color abnormalities in acquired deficits such as diabetes and that it is sensitive enough to detect regional retinal losses of sensitivity (e.g., as in central serous choroidopathy). The spatiochromatic visual evoked potential provides a systematic and sensitive indication of different color vision anomalies. PMID- 8350165 TI - Multivariate assessment of computer-analyzed corneal topographers. AB - Methodological aspects of multivariate statistical models to describe and to assess data from computer-analyzed corneal topographers (CACT) are considered. The data generated by repeated curvature mappings of calibrated steel balls are discussed in detail with the objective of formulating the basic questions and suggesting directions to assess data from clinical applications of CACT. The interpretation of seemingly straightforward concepts such as accuracy and precision is revisited with the objective of understanding its meaning in future clinical and experimental applications of CACT. Some of the statistical problems related to the analysis of corneal astigmatism based on CACT data are also discussed. PMID- 8350166 TI - Quantification of monocular optokinetic nystagmus asymmetries and motion perception with motion-nulling techniques. AB - When tested monocularly, strabismic and amblyopic subjects often show asymmetries of optokinetic nystagmus (OKN), with OKN being more readily elicited by temporal to-nasal than by nasal-to-temporal stimulus motion. We tested five visually normal subjects and ten strabismic and/or amblyopic subjects by use of motion nulling stimuli, which consisted of superimposed temporal-to-nasal and nasal-to temporal sinusoidal-grating components with a summed contrast of 100%. Both the direction of OKN and the subject's perceived direction of motion (PDM) were tested. Most normal subjects showed symmetrical OKN and PDM, but a rightward OKN bias was observed in one of the visually normal subjects. Temporal-to-nasal eye movement biases were seen in most strabismic and amblyopic subjects, whereas PDM biases were smaller and less frequent. The primary purpose of this study was to demonstrate the feasibility of quantifying OKN and PDM asymmetries in a diverse group of visually abnormal adults by use of the motion-nulling technique. Application of this technique to larger and more homogeneous clinical populations may contribute to the continued differentiation and characterization of variants of the visual disorders associated with strabismus and amblyopia and with other defects of binocular vision. PMID- 8350167 TI - Binocular enhancement of visual acuity. AB - Using a computerized test system, we compared binocular and monocular visual optotype acuity, varying both contrast and contrast disparity between the two eyes. When contrast was the same in the two eyes, binocular acuity was better than best monocular acuity by an average of 0.045 log minimum angle of resolution, or 11%. When contrast differed in the two eyes, binocular acuity in most but not all cases was still better than the monocular acuity of the eye that received the higher contrast. This binocular advantage became smaller but remained significant as contrast disparity became larger. These results are most simply explained by threshold contrast summation of high-spatial-frequency letter components. PMID- 8350168 TI - Contrast sensitivity and disability glare in the middle years. AB - Spatial contrast sensitivity and disability glare were measured in a large sample (n = 90, 30 per decade) of middle-aged subjects, aged 21-50 years, who had clear media and were ophthalmologically normal. We found no significant differences in the contrast sensitivities as a function of age in the middle years for (1) gratings generated on a monitor; (2) interference gratings generated in the retinal plane; (3) gratings in the presence of glare; and (4) mesopic increment thresholds with and without glare. The large sample size provides sufficient statistical power (0.8) for one to conclude that contrast sensitivity, optical quality, and foveal neural sensitivity are unlikely to vary more than 0.1 log unit between the ages of 21 and 50 in ophthalmologically normal subjects with clear media. PMID- 8350170 TI - The stability of temporary prosthetic base materials. I: Introduction, angular changes and dimensional stability. AB - The bases of occlusal rims and trial dentures should fit both the cast and the mouth accurately. The retention of shape and dimension of strips and sheets of grey and pink shellac, filled cold cure acrylic resin and wax were tested following moulding over stylised upper edentulous casts. The thermoplastic materials were softened over a flame or in a water bath. Specimens were prepared with and without folding along the long axes of the strips. The angles formed by the strips, the gap between the palate of the baseplates and casts and the linear dimension of the sheets were measured after moulding, after immersion in water at 37 and 45 degrees C and after 24 h at room temperature. The least angular change was shown by unfolded grey shellac, softened over a flame and moulded by finger pressure over an unwarmed cast, followed by folded specimens softened in water and moulded with the fingers over a prewarmed cast. The least gap developed beneath pink shellac softened in water and moulded by finger pressure over a warmed cast. The smallest dimensional change was shown by grey shellac softened in water and moulded by finger pressure over a warmed cast. Thus, optimally manipulated shellac materials exhibit less change after moulding than cold cure acrylic resin or modelling wax. PMID- 8350169 TI - Acoustic myography in the assessment of human masseter muscle. AB - The feasibility of examining electro-mechanical activity of the human masseter muscles using non-invasive recording techniques was examined in six healthy dentate adults (aged 34-57 years). Electrical activity of the muscle was examined by surface electromyography (EMG) and the mechanical activity, in the form of muscle sounds, was examined by acoustic myography (AMG). Bilateral recordings of EMG and AMG were made simultaneously using composite probes which were placed on the skin over the masseter muscles. A standardized pressure was applied to the probes via adjustable rods attached to a safety helmet. Pressures were monitored by strain gauges placed between the ends of the rods and the probes. With the subject seated, recordings of AMG and EMG were obtained during maximal jaw clenching for 4 s and the raw signals were stored on a computer. Of three maximal contractions performed, the last two were used in the analysis. The raw amplified signals underwent frequency analysis by fast Fourier Transform. Total activity was also assessed after amplification, full-wave rectification and integration, and repeatability of the results was assessed. The AMG frequency range was 6-15 Hz and was similar to values for other human skeletal muscles. The integrated values for EMG and AMG were repeatable on both sides of the face (IEMG, right r = 0.99, left r = 0.99; IAMG right r = 0.70, left r = 0.71). Simultaneous recordings of AMG and EMG from the masseter muscles may be useful for assessing electro mechanical muscle function but further validation studies are required before the technique can be used clinically. PMID- 8350171 TI - Elementary identification of a gnathosonic classification using an autoregressive model. AB - This was an investigation to determine the feasibility of an autoregressive (AR) model for establishing characteristic parameters from recorded occlusal sounds and develop their classification. Thirty four normal subjects with intact natural dentitions were selected for the study. The subjects' occlusal sounds from both sides of their faces respectively were sampled, and the gnathosonic classification (Class A, B and C) was established by observing the original recorded wave pattern and measuring the duration. Then, a 20 order AR model was calculated with the collected data, and the AR model coefficients were found to be similar to the indices of Bayes' discriminatory analysis. The total conformation rates of the modelled left and right occlusal sounds to the classification, estimated by Bayes' discriminant functions were 97.06% and 88.24% respectively. AR coefficients representing the characteristics of human occlusal sounds can be helpful in their classification and allow computer diagnosis of occlusal disorders. PMID- 8350172 TI - Measurement of the viscosity of irreversible hydrocolloids. AB - Three techniques have been used to assess the shear rate dependence of the viscosity of mixed alginate impression materials prior to setting. Two methods used a cone-plate viscometer, and one method was a capillary extrusion technique. Data from the three sets of experiments have been critically compared. It has been shown that an unset alginate material exhibits Bingham behaviour. PMID- 8350173 TI - Longitudinal study on occlusal force distribution in lower distal-extension removable partial dentures with conus crown telescopic system. AB - The purpose of this study was to examine longitudinal changes of the occlusal force distribution in lower distal-extension removable partial dentures with the conus crown telescopic system. Occlusal force applied to the denture and forces transmitted to the retainers were measured on several separate occasions from the insertion of new dentures to about 3 months after. The occlusal force distribution ratio to the retainers was calculated when a load of 20 N was applied to the denture. The results are summarized as follows: (i) The more posterior the loading point of occlusal force, the smaller was the ratio. When the occlusal force was applied to the most anterior artificial tooth, the ratio was 65-100% of the occlusal force. (ii) As the denture wearing time proceeded, the ratio was decreased. The smaller the ratio, the greater was the rate of its decrease. PMID- 8350174 TI - The production of shellac and its general and dental uses: a review. AB - An historical review of the general uses of shellac is presented and the various manufacturing processes, properties and chemical composition are discussed. The applications, advantages and disadvantages of shellac and its uses in dentistry are outlined. PMID- 8350175 TI - Taurodontism and length of teeth in patients with oligodontia. AB - Taurodontism and a reduced tooth length are reported to occur in patients with oligondontia. The aim of this study was to evaluate the occurrence of these factors in Dutch patients with oligodontia. Panoramic radiographs of 117 patients with oligodontia and 91 controls were collected. Taurodontism of the mandibular first molars was recorded and the length of cuspids, bicuspids and first molars of the mandible were measured. In patients with oligodontia 28.9% showed taurodontism of one or two mandibular first molars. The prevalence of taurodontism in normal Dutch subjects was 9.9%. No significant differences were found between the two sexes in both groups. Neither was there a significant difference in the unilateral and bilateral occurrence of taurodontism. The present findings supported the hypothesis that taurodontism may be the result of an ectodermal defect and a manifestation of developmental instability in patients with oligodontia. The length of mandibular cuspids and first molars in females were significantly reduced. In males only the lower right first molar was significantly reduced. The reduced length of the teeth may also be the result of a defect in ectodermal cells. Both taurodontism and a reduced length are of importance considering dental therapy. PMID- 8350176 TI - Complications in the tissue integrated prostheses components: clinical and mechanical evaluation. AB - Cases demonstrating complications in osseointegrated implant supported prostheses are described. These complications occurred in the prostheses framework or veneer, in the fixation screw, in the abutment post or screw as well as in the implant body. The two main reasons for the complications were lack of passive fitting between the restoration and the abutment; and destructive occlusal contacts. The destructive occlusal contacts may develop during the time of wear of the prostheses material or by changes in the opposite restoration. Overloading or bending moments exerted on the prostheses via these occlusal contacts resulted in loosening or fracture in one of the implant-prostheses components. The benefit of acrylic resin or composite material in reducing stresses in the light of the possible long-term, harmful occlusal changes that might develop as a result of their wear should be considered. PMID- 8350177 TI - Variables affecting the fracture toughness of resin-based inlay/onlay systems. AB - The fracture toughness of five different resin-based inlay/onlay materials was investigated by means of critical stress intensity factor (KIC) using the SEN three-point bending test procedure (BS 5447: 1977). KIC values were determined from specimens prepared by both the direct and indirect techniques. Tests were performed immediately, after 1 day, 1 month and 3 month time intervals. Also, fractured surfaces of specimens were observed using SEM photographs. PMID- 8350178 TI - Anterior digastric muscle responses to sudden unloading of the mandibular elevator muscles in younger and older adults. AB - The digastric motor responses in the unloading reflex were investigated in a sample of 10 younger and eight older dentate subjects. The occurrence of the pre collapse digastric activity (PDA) and the reflex events (burst of activity) following the mandibular unloading (DB) were studied separately. PDA was nearly consistent in half of the subjects of both groups. DB was clearly identified in 60% of the younger subjects, but in 54.2% of the older subjects. The mean latency of DB found in the younger subjects was 32.4 +/- 9.5 ms but 34.5 +/- 8.8 ms in the older subjects. For the latencies found we can infer that they are related to polysynaptic pathways. Also a slight tendency for decreased frequency of occurrence and increased latencies of DB is observed in the older age group. PMID- 8350179 TI - Reproducibility of tooth tapping rhythm in young and elderly dentate subjects. AB - The reproducibility of tooth tapping frequencies was measured in young and elderly dentate subjects. Six rates of tapping, i.e. 40, 60, 90, 120, 160 and 200 times per min, were practised to the accompaniment of a metronome for 15 s before recording. After a 15-s break, subjects were asked to reproduce the same rate of tapping without metronome accompaniment, and these movements were recorded. It was determined that the young subjects regulated tooth tapping frequencies by controlling velocity of mandibular movement. On the other hand, the elderly subjects regulated tooth tapping frequency by controlling opening width. PMID- 8350180 TI - Electrochromic behaviour of carotenoid molecules in nerve cell membranes: a resonance Raman study. AB - It was found that, following the depolarization of cell membranes of frog sciatic nerve, the 1521 and 1156 cm-1 resonance Raman (RR) bands of carotenoids showed an increase in intensity of 20%, 15% and 4% at excitation wavelengths of 488, 496.5 and 514.5 nm respectively. None of the bands revealed any change with excitation at 441.6, 457.9, 472.7 and 476.5 nm. These results can be explained by an electrochromic shift of the excitation profile of the RR bands by about 0.5 nm to the red. A dependence of the 1521 cm-1 band intensity on transmembrane potential was obtained. Under the effect of lanthanum ions, which are known to modify the surface charge of the membrane, the intensity of the Raman bands decreased by 15% 20% (excitation, 488.0 nm). The results obtained indicate that RR spectroscopy of carotenoids can be used to monitor changes in the transmembrane potential and surface charge of nerve cell membranes. PMID- 8350181 TI - Photosensitization with anticancer agents. 16. The photo-oxidation of hypocrellin A. A mechanism study using 18O labelling. AB - Hypocrellin A was selected as a representative structure to investigate the mechanism of photo-oxidation of perylenequinonoid pigments (PQPs). It was found that singlet oxygen plays a key role in the photo-oxidation of PQPs. The following processes were determined to be involved in the photo-oxidation of PQPs using 18O atom labelling. After the PQP is photoexcited, it tautomerizes and dissociates to produce the anion, which reacts with singlet oxygen generated during irradiation, resulting in the formation of an endoperoxide. The endoperoxide then rearranges to form a dioxetane which undergoes cycloreversion to produce the final product, a di-alpha-naphthoquinone. The factors affecting the photo-oxidation of hypocrellin A were also investigated, including the pH of the solution, nature of the solvent, irradiation wavelength and hydration phenomena. Of these factors, the extremely strong effect of pH on the photo oxidation of hypocrellin A may be used as a basis for the selective localization of hypocrellin A in tumor tissue. On the basis of the proposed mechanism for the photo-oxidation of PQPs, it may be possible to design and synthesize an optimal tumor-selective PQP photosensitizer for the photodynamic therapy of human tumors. PMID- 8350182 TI - Photoinduced proton transport mechanism in merocyanine-dye-probed planar lipid membranes. AB - Planar lipid membranes were used to study photovoltage generation after the incorporation of various merocyanine dyes. These dyes undergo photochemical isomerization on illumination and can act as a photon-driven facilitated proton transport system under suitable conditions. This system has the advantage of preventing back recombination of the photodissociated charges, thus improving its storage capacity. A sufficiently high photovoltage, with a long storage time and good reproducibility, was obtained with these dyes. The spectral studies indicate the formation of a 1:1 complex between dye and lipid molecules. Our results show that the strength and stability of complex formation increase with the hydrophobicity of the dye which, in turn, increase the magnitude and storage of the photovoltage generated in the system. PMID- 8350183 TI - Experimental studies on the mechanisms of tiaprofenic acid photosensitization. AB - Red blood cell lysis and histidine degradation, photosensitized by tiaprofenic acid (TIA), were investigated. Photohaemolysis was markedly enhanced in oxygenated solutions, but was also intense in the presence of nitrogen. Photohaemolysis was inhibited by butylated hydroxyanisole and reduced glutathione, but was unaffected by sodium azide, superoxide dismutase and mannitol. The TIA-induced photo-oxidation of histidine was greatly enhanced in the presence of oxygen and almost completely inhibited in solutions bubbled with nitrogen. Sodium azide, butylated hydroxyanisole and reduced glutathione inhibited the photodegradation of histidine. Phototoxicity to histidine was unaffected by mannitol and superoxide dismutase. The overall results suggest that molecular mechanisms involving free radicals and singlet oxygen are responsible for TIA-photosensitized reactions. These two in vitro models (photohaemolysis and histidine degradation) represent different mechanisms of phototoxicity, but complement one another in the investigation of potential phototoxic substances. PMID- 8350185 TI - Stereochemical factors in the transport and binding of photosensitizers in biological systems and in photodynamic therapy. AB - The uptake and biological activity of porphyrins and phthalocyanines in tumours were correlated with the geometrical features of the photosensitizer molecules. The data suggest that a critical distance of approximately 1.2 nm between oxygen atoms (originating in SO3-, COO- or OH substituents) characterizes a biologically active photosensitizer for photodynamic therapy. We propose that tubulin, which is available in large amounts during mitosis, is the main receptor molecule which binds these photosensitizers. Basic amino acid residues or tightly bound cations in tubulin or homologous proteins may act as binding sites on the receptor molecule. PMID- 8350184 TI - Photosensitization with methylene-linked porphyrin dimers. AB - The photodynamic therapy (PDT) efficacy of a series of porphyrin dimers linked by methylene groups was evaluated using the radiation-induced fibrosarcoma (RIF) tumor model. Longer chain length led to greater efficacy and increased dimer hydrophobicity. This result was correlated with the persistence of porphyrins in plasma, but not with tissue levels. PMID- 8350186 TI - Biochemical and morphological changes in Escherichia coli irradiated by coherent and non-coherent 632.8 nm light. AB - Irradiation of Escherichia coli cells with either coherent or non-coherent 632.8 nm light (4 J cm-2) causes a transient acceleration of cell proliferation, which is maximal about 60 min after the end of the phototreatment. The stimulatory effect is dose dependent and is especially evident in the case of defective E. coli strains which are in the logarithmic phase of growth, while it becomes less important when cells are exposed to non-coherent 600-700 nm light. Stimulated cells exhibit biochemical and morphological changes, such as an intensified synthesis of cytoplasmic membrane proteins, increased cell volume and ribosomal content, which are suggestive of an enhanced cell metabolism. PMID- 8350187 TI - Quantum yield and skin filtering effects on the formation rate of lumirubin. AB - Photocyclization of bilirubin to lumirubin in the skin of jaundiced infants exposed to blue-green light irradiation is considered to be the most important process for bilirubin elimination from the organism. The quantum yield phi LR of the bilirubin-->lumirubin photoreaction has been recently measured and found to vary with the excitation wavelength, with a peak at about 520 nm. The quantum yield phi ZE for the strongly competing reversible configurational photoisomerization of bilirubin has also been recently shown to be wavelength dependent and to decrease significantly in the long-wavelength part of the absorption band of bilirubin. These new data are taken into account to model the bilirubin photochemistry in vivo by using a simplified skin optical model based on the Kubelka-Munk theory. The rate kappa LR of formation of lumirubin has been evaluated for the case of a four-layer skin and for monochromatic and narrow-band coloured fluorescent lamps. The effects of long-wavelength increase in phi LR, decrease in phi ZE and skin optical losses all combine to shift significantly the optimal rate of formation of lumirubin towards the green. These results suggest that a significant improvement in phototherapy might be obtained with the introduction of new lamps emitting in the blue-green spectral region between 490 and 510 nm. PMID- 8350188 TI - Inhibition of dimer excision in repeatedly UV-irradiated Escherichia coli: its requirement for RecA protein and de novo protein synthesis. AB - In UV-irradiated Escherichia coli dimer excision was found to be inhibited by predamage (M. Sedliakova, F. Masek and J. Brozmanova, FEBS Lett., 23 (1972) 325 326) or overproduction of RecA protein, which suggests that the coating of the dimers by this protein may make them inaccessible to the excision nuclease (M. Sedliakova, K. Kleibl and F. Masek, Mutat. Res., 191 (1987) 13-16). We measured the levels of RecA protein and dimer excision in cells irradiated with (i) a single dose of 50 J m-2, (ii) two separate doses of 30 and 50 J m-2, post incubated with chloramphenicol; (iii) two separate doses of 30 and 50 J m-2, post incubated without chloramphenicol. Dimer excision was complete in the first two cases, but in the latter it was inhibited by 40%. At the time of active dimer excision, there were marked differences in RecA protein content between the cells irradiated with a single dose and cells irradiated with two separate doses (both post-incubated without chloramphenicol), which might account for the differences in dimer excision. However, relatively small differences in RecA protein content were found in cells irradiated with two doses and post-incubated with or without chloramphenicol, which could therefore not account for the differences in dimer excision. The data suggest that the inhibition of dimer excision involves some short-lived component(s) other than RecA protein. PMID- 8350189 TI - Studies on pharmacokinetics of sulfonated aluminum phthalocyanine in a transplantable mouse tumor by in vivo fluorescence. AB - The pharmacokinetic properties of sulfonated aluminum phthalocyanine (A1PCS) in mouse bearing transplantable S180 tumors were determined by an in vivo method. In vivo fluorescence measurements were made on the hind legs of mice, one leg bearing a tumor and the other, without a tumor, being used as a control. These in vivo data were compared with the results obtained from in vitro extraction fluorescence experiments. The results obtained by the two methods showed remarkable agreement, both procedures demonstrating that the concentration of A1PCS in the tumor was substantially higher than that in muscle. In both cases, the maximum tumor to muscle A1PCS concentration ratio occurred at 24-36 h after drug administration. The agreement between the in vivo and in vitro measurements shows that the in vivo fluorescence technique can be used successfully in pharmacokinetic studies of metallo-phthalocyanines in a superficial tumor model. The in vivo technique has the advantages of being rapid and convenient. PMID- 8350190 TI - Functional identification of al-3 from Neurospora crassa as the gene for geranylgeranyl pyrophosphate synthase by complementation with crt genes, in vitro characterization of the gene product and mutant analysis. AB - In this work the Neurospora crassa al-3 gene function was determined. Geranylgeranyl pyrophosphate (GGPP) synthase activity was measured in al-2 FGSC 313 and al-3 RP100 FGSC 2082 mutant strains by in vitro synthesis methods. This experiment showed that al-3 RP100 mutant expresses a reduced GGPP synthase activity. The mutated al-3 gene was cloned and sequenced; a single missense mutation was found changing serine into asparagine. Genetic complementation was performed by Escherichia coli transformation, with clusters of crt genes from Erwinia uredovora. Carotenoid accumulation was observed in E. coli transformants when the N. crassa al-3 gene substitutes the GGPP synthase gene (crtE) in the carotenogenic crt cluster. Cell-free studies with E. coli transformants gave direct evidence of the function of the al-3 protein as GGPP synthase and indicated that a short-chain prenylpyrophosphate, such as dimethylallyl pyrophosphate, is the genuine substrate. PMID- 8350191 TI - Phototransformations of porphyrins in aqueous and micellar media. AB - Porphyrin photoproducts with absorption maxima at 640 and 660 nm are formed in aqueous and micellar solutions during light exposure. Changes in the dimethoxyhaematoporphyrin (DMHp) Soret band on irradiation suggest that the photoproduct (640 nm) formation is conditioned by the "sandwich"-type self associates. The formation of the photoproduct (660 nm) in micellar haematoporphyrin (Hp) and photosan-3 (PS) solutions and its formation in small amounts in phosphate-buffered solution (PBS), is related to the presence of covalently linked porphyrin structures and/or interaction with surfactant molecules. PS is the most photostable of the three investigated porphyrins. Its photostability is probably due to the presence of covalently linked "sandwich" type aggregates. PMID- 8350192 TI - Fluorescence properties of subtilisins and related proteinases (subtilases): relation to X-ray models. AB - The fluorescence properties of six subtilases with known X-ray structure were determined using the same experimental conditions and instrumentation. The steady state and nanosecond lifetime measurements were performed on purified samples of phenylmethanesulphonyl-inhibited proteinases in the presence of 20 mM CaCl2 which stabilizes the molecules. The tryptophan emission quantum yield strongly depends on the local environment and varies from 0.02 to 0.10. The efficiency of tyrosine to-tryptophan energy transfer also varies (0%-70%) in the different enzymes; the most efficient transfer was observed for thermitase. Experiments with nanosecond excitation indicated that the tryptophan fluorescence of subtilases decays with two exponential components. The X-ray models of the six proteinases were analysed in the region of the tryptophyl residues and were used to explain the observed properties. PMID- 8350193 TI - Artificial sunlight irradiation induces ultraweak photon emission in human skin fibroblasts. AB - Photons participate in many atomic and molecular interactions and changes in the physical universe. In recent years sophisticated detection procedures for the measurement of ultraweak photons in a variety of different cells have been performed leading to the conclusion that plant, animal and human cells emit ultraweak photons. Using an extremely low-noise, high-sensitive photon-counting system, which allows maximal exploitation of the potential capabilities of a photomultiplier tube, ultraweak photons were quantitated in human skin fibroblasts. It was found that light from an artificial sunlight source induces ultraweak photon emission in these cells. However, the results demonstrate that this induction is significantly lower in normal fibroblasts compared with those obtained from a donor suffering from xeroderma pigmentosum disease group A, a disease characterized by deficient repair of DNA. The largest increase in ultraweak photon emission after UV exposure was measured in mitomycin-C-induced post-mitotic xeroderma pigmentosum cells which showed 10-20 times higher ultraweak photon intensities than mitotic UV-irradiated normal cells. These data suggest that xeroderma pigmentosum cells tend to lose the capacity of efficient storage of ultraweak photons, indicating the existence of an efficient intracellular photon trapping system within human cells. PMID- 8350194 TI - In vivo photoproduct formation during PDT with ALA-induced endogenous porphyrins. AB - The administration of 5-aminolevulinic acid (ALA) in tumor-bearing nude mice leads to the formation of the fluorescent, photounstable photosensitizer protoporphyrin IX in tumor tissue. On-line fluorescence spectroscopy during photodynamic therapy (PDT) shows the in vivo formation of chlorintype photoproducts of protoporphyrin. The fluorescence of protoporphyrin as well as its photoproducts is bleached completely at the end of the PDT (100 J cm-2, 630 nm). These findings were also verified using ultrashort laser pulses and time correlated single-photon counting. A photinduced shortening of the decay times and decrease in the integral fluorescence intensity were measured in vivo due to the photodestruction of the endogenous photosensitizer protoporphyrin IX in the tumor. PMID- 8350195 TI - Effect of in vivo He-Ne laser irradiation on biogenic amine levels in rat brain. AB - In order to elucidate the metabolic modifications induced in rat brain by low power He-Ne laser irradiation in vivo, the variations in the biogenic amine levels in cortex, striatum and hippocampus were studied. Noradrenaline (NA), dopamine (DA) and serotonin (5-HT) were evaluated by HPLC-EC on irradiated rats, untreated rats (controls) and rats which had undergone restraint stress (stressed). The results obtained on groups of four to eight rats assayed individually showed that irradiation caused a strong increase in 5-HT in striatum and hippocampus, a small but significant decrease in NA in cortex, and DA levels were not significantly affected. Restraint stress per se led to a considerable decrease in 5-HT and DA in striatum and hippocampus, but did not significantly alter the NA levels. PMID- 8350196 TI - The cationic meso-substituted porphyrins: an interesting group of photosensitizers. PMID- 8350197 TI - Reflections on type I photodynamic damage. PMID- 8350198 TI - Nontransplant surgical options for management of the short bowel syndrome. PMID- 8350199 TI - Gastric volvulus after anterior gastropexy. PMID- 8350201 TI - Repaired peroxisome assembly: the future begins now. PMID- 8350200 TI - Candy bezoar: an unusual cause of food bolus bezoar. PMID- 8350202 TI - DNA-based diagnosis of Wilson disease. PMID- 8350203 TI - Corticosteroid drugs and inflammation: the endothelial-leukocyte interface as a target for therapeutics. PMID- 8350204 TI - Rectal polyps in Proteus syndrome. PMID- 8350205 TI - Incidence of gastroesophageal reflux with casein and whey-based formulas. PMID- 8350206 TI - Helicobacter pylori infection in children. PMID- 8350207 TI - Portal hypertensive gastropathy in children. AB - We endeavored to determine the frequency and clinical characteristics of portal hypertensive gastropathy (PHG) in children with cirrhotic and noncirrhotic portal hypertension. Medical records of all patients with portal hypertension undergoing upper GI endoscopy during a 7-year period were retrospectively reviewed. PHG was defined as absent, mild, or severe by previously established criteria. Twenty-two patients with portal hypertension (17 cirrhotic, 5 noncirrhotic) were identified. In the group of 17 cirrhotic patients, PHG was noted in four at initial endoscopy (three mild, one severe) and in seven (two mild, five severe) during follow-up. Severe PHG was seen in one patient with noncirrhotic portal hypertension at presentation; in two patients, mild PHG developed during follow-up. In the 14 patients in whom PHG was noted, gastric mucosal disease developed in nine in whom no sclerotherapy was performed and in five patients treated with sclerotherapy. The size of varices, history of variceal bleeding, and presence or absence of hypersplenism did not appear to be related to the development of PHG. None of seven patients with mild PHG and two of seven patients with severe PHG bled from their gastric mucosa. We conclude that PHG is commonly observed in children with cirrhotic and noncirrhotic portal hypertension. Mild PHG appears to have little clinical significance, while severe PHG may cause bleeding. PHG may develop with or without sclerotherapy. PMID- 8350208 TI - The diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography in children. AB - We performed 121 endoscopic retrograde cholangiopancreatographies (ERCPs) in 92 patients (60 girls and 32 boys), aged 4 months to 19 years, as part of diagnostic evaluation for suspected pancreatic or biliary tract disease or as therapeutic intervention. ERCP was successful in 116 attempts. The most common indications were recurrent pancreatitis (35 children), nonresolving acute pancreatitis (20), unexplained elevated amylase or lipase (19), postcholecystectomy syndrome (14), and elevated biliary tract enzymes (12). One hundred and one ERCPs were performed for more than one indication. The most common findings included chronic pancreatitis (26 cases), pancreas divisum (14), dilated pancreatic duct (10), gallstones or sludge (8), and abnormal common bile duct (8). Complications were uncommon and usually minor. ERCP is a safe and helpful procedure in the evaluation of suspected pancreatic and biliary tract disease in children and frequently allows for nonoperative treatment of these disorders. PMID- 8350209 TI - Ulcerative colitis in children 10 years old or younger. AB - The onset and course of ulcerative colitis diagnosed in 38 children at or before 10 years of age were reviewed. The mean age at onset was 5.9 years. A family history of inflammatory bowel disease was present in 24% of patients, and 13% had a history of cow milk allergy in infancy. Initially, by radiologic or colonoscopic studies, 71% had total colonic disease, 13% had left-sided colitis, and 6% had proctitis; extensive examination was not performed in 4 patients. Four patients (11%) presented with severe colitis, 14 (37%) with moderate colitis, and 20 (53%) with mild colitis. The most frequent symptoms were abdominal pain (94%), diarrhea (84%), and rectal bleeding (84%). Between 2 and 10 years after diagnosis, 89% of children had total colonic disease and 11% had left-sided disease. All four patients with severe disease at onset responded to medical therapy with one having a colectomy 15 years later with pathology consistent with Crohn's disease. Of those with moderate disease, half had infrequent moderate recurrences and half had intermittent mild disease. One patient had colectomy at 21 years for intractable disease. Of the 20 with mild disease, 16 continued to have intermittent mild recurrences, 1 had chronic mild disease, 2 had moderate recurrent disease, and 1 has remained asymptomatic for 5 years. Psychiatric disturbances requiring therapy were identified in 5 (13%) children. Results are encouraging: after the first 2 years of illness, two thirds of the children have had subsequent mild colitis with infrequent relapses and three quarters consider their life to be of good quality. PMID- 8350210 TI - Effects of cerulein and epidermal growth factor on pancreatic growth in the reserpinized rat model. AB - This study was undertaken to determine the effect of reserpine on rat pancreatic growth, to evaluate if reserpine-caused alterations can be prevented by epidermal growth factor (EGF) and/or cerulein treatment, to evaluate the time course of rat pancreas recovery after reserpine, and to determine if EGF and/or cerulein treatment can accelerate such a recovery. In the first experiment, three groups of male Sprague-Dawley rats (250-265 g) were used. Ad libitum-fed control animals received the reserpine vehicle, and one experimental group received reserpine (1 mg kg-1 day-1 for 7 days) while the other, pair-fed group received the reserpine vehicle with a reduced amount of food to result in malnourishment. Rats from each of these three groups were also assigned to one of four treatments consisting of saline, EGF (10 micrograms kg-1), cerulein (1 microgram kg-1), or a combination (same doses) twice a day for 7 days. In the morning of the 8th day, after an overnight fat, rats were killed. In the second experiment, rats were selected and treated with reserpine or the vehicle as described in experiment 1; after the 7 day treatment, a first cohort of animals was allowed a 30-day recovery period. Three other groups (an ad libitum-fed control, a pair-fed, and a reserpine group) were allowed a 6-day recovery period during which they were treated subcutaneously, twice a day, with either saline, EGF (10 micrograms kg-1), cerulein (1 microgram kg-1), or a combination (same doses). On the morning of the 31st or 7th day, after an overnight fat, rats were killed. After death, all pancreata were examined for weight and protein, amylase, chymotrypsinogen, RNA, and DNA content. In the ad libitum-fed control group, EGF caused pancreatic hypertrophy, whereas cerulein was associated with hypertrophy and hyperplasia. In the pair-fed malnourished group, the EGF effect was limited to slight increases in pancreatic weight and cell mass whereas cerulein caused hypertrophy; EGF plus cerulein caused pancreatic hyperplasia. In the reserpine group, EGF had no effect, whereas cerulein caused pancreatic hypertrophy and an increase in DNA content above the reserpine control. After 30 days of recovery, pancreata of pair fed animals and those of reserpine-treated animals were comparable with those of the ad libitum-fed control rats with the exception of amylase levels, which remained reduced in the reserpine group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350211 TI - Influence of orally administered epidermal growth factor on normal and damaged intestinal mucosa in rats. AB - The effect of orally administered epidermal growth factor (EGF) on the mucosal growth and hydrolase activity of normal and damaged small intestine was examined in rats. Adult rats fed EGF daily at 10 times the estimated daily intake of EGF from human milk showed increases in specific activity but not total activity of various brush-border hydrolases with unaffected mucosal protein content and villus-to-crypt ratios through day 9. Ingestion of EGF for 13 days resulted in significant decreases in mucosal protein content without changes in villus height or hydrolase activity. The effect of oral EGF on recovery of damaged intestine was studied in rats fed a liquid diet supplemented with EGF at 0, 1, 10, or 20 times the estimated daily intake from human milk after treatment with methotrexate (MTX) to induce acute intestinal injury. Animals treated with MTX showed significant reductions in body weight and small intestinal villus height, mucosal protein content, and hydrolase activities through day 6 posttreatment. Daily ingestion of EGF did not affect the MTX-induced reductions in mucosal protein content and hydrolase activity by day 3 but caused significant increases in mucosal disaccharidase and leucine aminopeptidase activity by day 6 at the 1- or 10-times human milk EGF levels. Similar changes were not observed in MTX treated rats fed the 20-times human milk level of EGF. These studies suggest that oral EGF is capable of modulating mucosal protein levels and stimulating enterocyte hydrolase expression during repair of the intestinal mucosa. PMID- 8350212 TI - Is histological diagnosis of neuronal intestinal dysplasia related to clinical and manometric findings in constipated children? Results of a pilot study. AB - Neuronal intestinal dysplasia (NID) of the colon has been reported in adults and children with chronic constipation. However, it is unknown whether these histological abnormalities are related to the severity of symptomatology or the findings of anorectal manometry. We studied 57 children (2 weeks to 17 years old, 33 boys) who had chronic constipation and/or soiling or obstructive symptoms early in life and evaluated anamnestic data, symptoms, outcome after 6 months of conventional therapy, rectal biopsies for signs of dysganglionosis, and results of anorectal manometry. In cooperative patients, defectaion dynamics were recorded during manometry with simultaneous surface electromyogram of the external anal sphincter. In 30 older patients, severity of constipation was assessed by measurement of colonic transit time with radiopaque markers. Histology confirmed Hirschsprung's disease in nine (excluded from further analysis), hyperganglionosis of the plexus submucosus (classic NID) in six, heterotopic ganglion cells without hyperganglionosis (abortive NID) in 18, and no signs of dysganglionosis in 24 patients. The rectoanal inhibitory reflex was more often absent or abnormal in children with classic NID (six of six) and abortive NID (11 of 17) compared with children with normal histology (four of 22) (p < 0.001). All other manometric parameters analyzed, colonic transit times, and clinical outcomes were not related to histological diagnosis. In contrast, the severity of constipation and outcome was significantly worse in children with abnormal defecation dynamics. These results suggest that histological signs of NID in the submucous plexus are of uncertain value in assessing the clinical picture and should not influence decisions concerning further treatment, especially surgical interventions. PMID- 8350213 TI - Feeding resistance and gastroesophageal reflux in infancy. AB - Resistance to oral feedings occurring during the course of chronic gastroesophageal reflux (GER) in infants has received little attention in the literature. Accordingly, we reviewed the clinical courses of 600 infants of < 24 months of age with GER seen over an 8-year period to determine the prevalence and course of this problem. After excluding infants with severe neurologic disease, craniofacial disorders, or a history of esophageal surgery, 25 infants were found to have resistance to oral feedings that was severe enough to warrant tube feedings for nutritional support. Sixteen of these 25 infants had a history of resistance to oral feeding antedating a diagnosis of GER, whereas nine developed resistance to feeding during the course of therapy. Gestational age, age at onset of GER symptoms, severity of GER, presence/severity of esophagitis, type of medical therapy, need for fundoplication, or postfundoplication complications were similar in these two groups. When the clinical records of these 25 infants were compared to an age- and sex-matched infant population with GER but without feeding resistance, no differences were noted in severity of GER or the presence/severity of esophagitis. However, failure to thrive and the need for fundoplication were significantly more common in the feeding resistance group (p < 0.001). Among those infants with neurodevelopmental evaluation, mild delay was seen more commonly in the infants with feeding resistance but fell short of statistical significance (p = 0.08). Our observations suggest that resistance to oral feedings is an uncommon but severe problem associated with GER in infancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350214 TI - Chromium and parenteral nutrition in children. AB - Chromium (Cr) dosage was assayed in i.v. nutrition, serum, and losses of five children on total parenteral nutrition for > or = 4 weeks. The Cr supply (4.7 +/- 1.2 micrograms/kg/day) was above recommended levels (0.5 microgram/kg/day). Serum (18.2 +/- 1.8 micrograms/L) and urine (37.4 +/- 10.5 micrograms/L) were also higher than control values (0.7-0.9 microgram/L and 0.2-0.8 microgram/L, respectively). Serum and urine Cr concentrations displayed a positive correlation. Serum Cr and Fe showed a negative correlation. These results confirm the potential toxicity of Cr previously reported in animals. Cr levels of i.v. nutrition solutes should be checked thoroughly. PMID- 8350215 TI - Dietary intake and nutritional treatment in childhood Crohn's disease. AB - Dietary intake was assessed in 24 children with active Crohn's disease. Seventeen of the children were sex and height matched with healthy siblings of other patients. The mean energy intake was 1,764 KJ/day (420 kcal/day) lower in patients during relapse than controls (p < 0.05). All 24 children entered a randomised controlled trial of high-dose steroids compared to an elemental diet. The elemental diet was well tolerated orally in most cases; only one patient required nasogastric administration. There was a similar improvement in disease activity and duration of remission in both groups regardless of the site of disease. Subsequent growth velocity was significantly better in the group treated with the elemental diet despite a greater and more sustained increase in energy intake in the group treated with steroids. Reintroduction of specific foods in the elemental diet group initially caused symptoms in three children but were subsequently tolerated. During remission, there was no significant difference in energy intake, but vegetables were consumed significantly less frequently (p < 0.01) and confectionery significantly more frequently (p < 0.05) when patients were compared with their own siblings. PMID- 8350216 TI - Relationship between plasma triglycerides and apolipoprotein CII in infants during the first year of life. AB - Plasma triglyceride and apolipoprotein CII (apo CII) levels were measured in normal full-term infants and low-birth-weight infants at birth (from umbilical cord blood at 0 weeks), as well as at 2, 3, 4, 8, 24, and 48 weeks of age, and the relationship between plasma triglyceride and apo CII levels was studied. In both full-term and low-birth-weight infants, the plasma triglyceride and apoprotein CII levels were very low at birth, but they increased rapidly thereafter in the full-term infants and somewhat more slowly in the low-birth weight infants. Both triglyceride and apoprotein CII levels became stable from 3 weeks of age in full-term infants and from 8 weeks in low-birth-weight infants. When the logarithmic values of triglyceride and apoprotein CII levels were compared, they showed a close correlation, and slopes of regression lines were 0.62 in full-term infants aged 0-2 weeks, 1.04 in full-term infants aged 3-48 weeks, 0.56 in low-birth-weight infants aged 0-4 weeks, and 1.04 in low-birth weight infants aged 8-48 weeks. These results suggest that there may be some differences in triglyceride transport between full-term infants aged 0-2 weeks and 3-48 weeks as well as between low-birth-weight infants aged 0-4 weeks and 8 48 weeks. PMID- 8350217 TI - Breast-feeding habits among Jewish and Arab mothers in Hadera County, Israel. AB - A survey of breast-feeding habits of Jewish and Arab mothers was carried out in Hadera county in Israel. Jewish mothers breast-fed their babies approximately 3 months, while Arab mothers did so for 5 months. The rate of breast-feeding among Jewish and Arab mothers was 84% and 94.4%, respectively. The results indicated that education, previous experience, enjoyment, husband's encouragement, previous information about the importance of breast-feeding, belief that breast-feeding strengthens the mother-child relationship, and the convenience of breast- over bottle-feeding were all factors that had an impact on breast-feeding habits among Jewish but not Arab mothers. Breast-feeding as a means of birth control, religion, and impairment of the breast's shape were factors that had no effect on either Arab or Jewish mothers. Complications during pregnancy and cesarean delivery decrease the probability of breast-feeding in Arab and Jewish mothers. Jewish mothers stopped breast-feeding because of insufficient milk, fatigue, work obligations, and physician's recommendation. Among Arab mothers the main reasons were insufficient milk, physician's recommendation, baby's refusal, and nipple problems. Jewish mothers who decided not to breast-feed stated that the reasons were previous experience with insufficient milk, nipple problems, and unpleasant feelings. The few Arab mothers who did not breast-feed cited medical or nipple problems. PMID- 8350218 TI - The nutritional value of a whey hydrolysate formula compared with a whey predominant formula in healthy infants. AB - Forty-five healthy infants were included in a double-blind randomized prospective study comparing the nutritional value of two formulas. One group received a whey predominant formula (n = 20); the other group received a whey hydrolysate formula (n = 25). Four infants of the whey hydrolysate group were dropped because they refused the formula. Although the mean daily volume intake was smaller with the whey hydrolysate formula compared with the whey-predominant formula (p < 0.001), the weight gain in the two groups after 13 weeks was identical (27.2 g/day in both groups; the mean difference in weight gain between the groups after 13 weeks was only 8 g). Length gain at 13 weeks was 10.4 cm in the whey-predominant formula group and 10.8 cm in the whey hydrolysate formula group (p = NS). After 13 weeks, blood was sampled for hemoglobin, hematocrit, red blood cell count, white blood cell count, lymphocytes, glycemia, proteins, albumin, prealbumin, calcium, phosphorus, urea, creatinine, iron, iron-binding capacity, zinc, and vitamins A and E. Except for the iron-binding capacity, zinc, urea (in plasma as well as in urine) (all three were higher in the whey hydrolysate group), no significant differences were found. According to these results, exclusive feeding of the whey hydrolysate formula from birth to 3 months of age to healthy infants appears to result in an adequate nutritional status, as assessed at 3 months of age. PMID- 8350219 TI - Zinc supplementation in very-low-birth-weight infants. AB - Inadequate zinc intake may lead to poor growth and developmental outcome in very low-birth-weight (VLBW; < 1,500 g) infants. Fifty-two infants (mean birth weight, 1,117 +/- 287 g; mean gestational age, 29 +/- 2.9 weeks) were randomly allocated to two groups. SUPP infants received a regular term formula plus zinc supplements (4.4 mg/L; final content, 11 mg/L); PLAC infants received the same formula plus placebo (final content, 6.7 mg/L). Infants started their formula at 1,853 +/- 109 g and consumed the formula for 6 months. All subjects were evaluated at 3, 6, 9, and 12 +/- 0.75 months corrected-for-gestational-age. At each evaluation, weight, length, and head circumference were measured, a Griffiths developmental assessment was performed, and a blood sample was taken. Higher plasma zinc levels (p < 0.05) were found in the SUPP group at 1 and 3 months, and improved linear growth velocity was found in the SUPP group over the study period for the whole group as well as for girls alone. Maximum motor development scores were higher (p = 0.018) in the SUPP (98 +/- 10) than the PLAC (90 +/- 8) group, indicating that increased zinc intake in early infancy may be beneficial to VLBW infants. PMID- 8350220 TI - Ocular implications of long-term prednisone therapy in children. AB - We compared 23 patients (ages 4 to 18 years) who were receiving long-term oral prednisone therapy with 31 normal controls (ages 7 to 16 years). Indications for corticosteroid treatment included renal transplant in 11 patients, nephrotic syndrome in 7, glomerulonephritis in 4, and vasculitis without renal disease in 1. The mean duration of prednisone therapy was 5.0 +/- 3.5 years, and the mean dose at the time of examination was 0.29 +/- 0.18 mg/kg/day. Mean intraocular pressure was 16.0 +/- 3.0 mm Hg (range, 12 to 25 mm Hg) in the prednisone group and 15.4 +/- 2.1 mm Hg (range, 12 to 20 mm Hg) in the control group. The difference between the means was 0.6 mm Hg (P = 0.35). Posterior subcapsular cataracts were present in seven (30%) of the prednisone patients, but in none of the controls (P = .001). None of the cataracts were visually significant. We found no evidence that pediatric patients on long-term, low-dose prednisone have higher intraocular pressures (IOPs) than normal children, although they are more likely to develop posterior subcapsular cataracts. PMID- 8350221 TI - Progressive overcorrection after inferior rectus recession. AB - We reviewed 67 cases of inferior rectus muscle recession. In 14 cases, the hypotropia was corrected to a satisfactory alignment in the immediate postoperative period followed by a progressive overcorrection (hypertropia). Patients with thyroid eye disease were at highest risk for progressive overcorrection, as 9 of 18 (50%) developed the problem. Patients undergoing adjustable suture were at a higher risk for development of the overcorrection, as 1 of 35 (3%) surgeries done with standard techniques had the overcorrection while 13 of 32 (41%) done on an adjustable suture had the problem. However, the actual act of adjustment was found not to be a predisposing factor. Also, operating upon multiple muscles was found not to be a risk factor for the complication. Once progressive overcorrection occurred, it was more difficult to correct when the patient had thyroid eye disease. We also reviewed 77 consecutive cases of superior, lateral, and medial rectus muscle recessions and found no cases of progressive overcorrection. PMID- 8350222 TI - Conjunctival reaction using adjustable sutures: a comparison of the cinch and bow knot methods. PMID- 8350223 TI - The effect of torsional muscle dysfunction and surgery on eye position under general anesthesia. AB - Under general anesthesia, normal eyes exhibit 2.0 degrees to 2.5 degrees of extorsion. To investigate the effect of torsional muscle dysfunction and surgery on eye position under general anesthesia, we measured the torsional change before and after torsional muscle surgery in 26 eyes of 18 patients with clinical torsional muscle dysfunction. Under general anesthesia, compared with normals, eyes with preoperative intorter overaction or extorter underaction demonstrated a significant intorsional change (P < .01). However, eyes with intorter underaction or extorter overaction did not demonstrate a significant extorsional change. Postoperatively, while patients remained under general anesthesia, intorter weakening procedures produced measurable extorsion while intorter strengthening procedures and extorter weakening procedures produced measurable intorsion. Superior oblique tenotomy produced a greater net torsional change than inferior oblique weakening surgery (P < .01). Under general anesthesia, eyes with preoperative torsional muscle dysfunction exhibit torsion in the direction consistent with the dysfunction. After surgery on the torsional muscles, a measurable torsional effect can be demonstrated while the patient is still under general anesthesia. PMID- 8350224 TI - A comparison of the success rates of resident and attending strabismus surgery: discussion. AB - Residency training involves surgery by resident surgeons at various levels of experience and proficiency, supervised by an experienced attending physician. We reviewed the results of strabismus surgery performed at four institutions with two residency training programs. Five hundred twenty-two cases with follow up greater than 6 weeks were evaluated. These cases included 315 attending procedures and 207 resident procedures under direct attending supervision. Success was defined as a strabismic deviation of 8 prism diopters or less. Average postoperative follow up was 57 weeks and did not differ between groups. There was no statistical difference between the resident success rate of 58% (121/207) and the attending success rate of 69% (217/315) after adjusting for population differences. The average final deviation of the patients postoperatively was 7 delta for the attending group and 10 delta for the resident group. Amblyopia was significantly more frequent in the resident cases (P < .001). Adjustable sutures were used significantly more often in attending cases (P < .0001). This study supports the premise that resident strabismus surgery is as successful as attending surgery. (Abstract reproduced from Wisnicki HJ, Repka MX, Raab E, et al. A comparison of the success rates of resident and attending strabismus surgery. PMID- 8350225 TI - Secondary exotropia: a retrospective analysis of matched cases. AB - Secondary exotropia, that is exotropia following surgery for esotropia, remains frustratingly common, even among experienced strabismologists. In this study, we have compared a group of secondary exotropia cases with a matched group of cases of residual esotropia. Of the factors analyzed, only the presence of an A- or V pattern preoperatively (P = .0077), the presence of limited postoperative adduction (P < .001), and postoperative binocular function (P = .0073) identified the secondary exotropes. The presence of reduced adduction postoperatively in subjects with secondary exotropia was a poor prognostic sign with 11 of the 13 cases requiring further surgery for poor cosmesis. The authors suggest two subclassifications of secondary exotropia. PMID- 8350226 TI - Augmented surgery for esotropia associated with high hypermetropia. AB - Historically, surgical formulas for the management of accommodative esotropia have been based on the residual deviation with full hypermetropic correction. This "standard surgery" has resulted in a high incidence of undercorrection. In response to the large number of undercorrections with standard surgery, the authors have devised a formula for augmenting the amount of rectus recession based on the average of the near deviation with and without correction. In this study, we compare augmented surgery to standard surgery in patients who underwent bilateral medial rectus recessions for residual esotropia after prescribing full hypermetropic spectacle correction. Seventy patients with acquired esotropia after 6 months of age, and hypermetropia of +3.00 or more, were retrospectively studied. Thirty of these patients had undergone standard surgery, while 40 had augmented surgery. The follow up on each group was at least 1 year. Of the 30 patients in the nonaugmented group, 22 (74%) had postoperative deviations of 10 prism diopters or less with 8 (26%) showing a significant undercorrection. Of the 40 patients who received augmented surgery, 35 (88%) had postoperative deviations of 10 delta or less and 5 (12%) were exotropic while wearing full hypermetropic correction. Of the 5 patients with a consecutive exodeviation while wearing full hypermetropic correction, 2 corrected to orthotropia by reducing the spectacle correction by +1.50 diopters and +1.25 D (93% success), 2 were converted to orthotropia by removing +3.00 spectacle correction (97% success), and 1 continued to have an intermittent exodeviation even after removing spectacle correction. This brought the overall success rate for augmented surgery to 98%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350228 TI - Macular hypoplasia in familial cataracts. PMID- 8350227 TI - Posterior lenticonus: clinical patterns and genetics. AB - Posterior lenticonus is an uncommon abnormality in the shape of the crystalline lens, characterized by a spheroidal or conical protuberance affecting the posterior lens surface. It may be unilateral or bilateral. A male infant with bilateral posterior lenticonus is described, whose mother was found to have bilateral sutural cataracts. The association of cataracts with posterior lenticonus and the genetics of the condition are discussed. PMID- 8350229 TI - Ocular and systemic characteristics of Duane syndrome. AB - The clinical features of 63 patients with Duane syndrome are described in this report. All data in the study were gathered retrospectively except for measurements of vertical palpebral fissure and axial eye length, which were investigated prospectively. The following new aspects of the syndrome are emphasized: 1) In most cases with heterotropia, the angle of deviation was not large (< or = 25 prism diopters). 2) Visual acuity of 0.66 (20/30) or better was recorded in 94% of the affected eyes. 3) Smaller palpebral fissure (by 1 mm or more) of the affected eye was measured in primary position among 9 of 40 (22%) unilateral cases. 4) The axial length of the affected eye (mean, 22.8 +/- 0.6 mm) was not significantly different from the uninvolved eye. 5) Two cases of heterochromia iridis (3.2%) were found among the Duane syndrome patients. 6) A 4.8% prevalence of high-tone hearing loss was detected, in addition to 4.8% of sensorineural deafness. PMID- 8350230 TI - Insertion site dynamics and histology in a rabbit model after conventional or suspension rectus recession combined with ipsilateral antagonist resection. AB - We have used a rabbit model to study insertion movement, rotational forces, disinsertion forces, and histology of the surgically created insertion site after recession of the inferior rectus (IR) using a conventional (CONV) or suspension (SUS) technique combined with an ipsilateral superior rectus (SR) resection. During the 5-week observation period, the CONV and SUS recessed IR showed an initial posterior movement followed by an anterior movement while all resected SR had an initial posterior movement which remained stable. SR rotational forces increased and IR remained constant throughout the 5-week observation period. There were no rotation force differences between the SUS and CONV recession techniques. Disinsertion forces showed an initial large decrease in force followed by a gradual increase to preoperative levels by 3 postoperative weeks. Disinsertion force differences between the CONV and SUS recessions were observed for 5 weeks after surgery. Histologic analysis showed a delayed inflammatory response on the SUS recession compared to the CONV recession and at the middle of the insertion compared to the poles which was minimized by 3 weeks after surgery. PMID- 8350232 TI - Visual loss in infantile osteopetrosis. AB - Osteopetrosis should be considered in an infant with unexplained visual loss. In particular, the possibility of this diagnosis must be intimated to the radiologist involved in the investigation of the child. PMID- 8350231 TI - Aneurysmal bone cyst: report of a case mimicking orbital tumor. AB - Aneurysmal bone cysts are rare bone tumors which normally affect the vertebral region or long bones. Involvement of facial bones is uncommon. Although nonneoplastic, these lesions are expansile and may cause local destruction of bone and soft tissues. When making the diagnosis, it is imperative to consider the clinical, radiologic, and histologic features of the entity to avoid confusion with other possibly malignant giant cell tumors. We report an unusual case involving the orbit in a 2 1/2-year-old girl. PMID- 8350233 TI - Pseudodistichiasis as a manifestation of anhidrotic ectodermal dysplasia. PMID- 8350234 TI - Caution, nurse practitioners. PMID- 8350235 TI - The eyes have it: visual attention as an index of infant cognition. AB - The purpose of this article is to provide the pediatric nurse practitioner with an introduction to the literature on the use of visual-attention measures to screen for cognitive deficits in the infant. These measures rely on an infant's preference for novelty, that is, the tendency to look at a new stimulus rather than a stimulus the infant has already seen. Individual differences in novelty preference among infants are related to later intelligence. Novelty preference measures may be particularly useful as an adjunct to developmental assessment of infants with motor impairment, because these infants may not have the motor skills to perform tasks of traditional sensorimotor-based assessments. PMID- 8350236 TI - Anemia as an indicator of nutrition in children enrolled in a Head Start program. AB - A retrospective chart review was conducted on the records of 467 children who were enrolled in the Head Start program in Alachua County, Florida, which is one of four counties in Florida cited among the 150 worst "hunger counties" in the United States by the Harvard University School of Public Health. The children were examined in the 1989-1990 school year by a team of nurse practitioners, and the data were analyzed to determine the incidence and distribution of anemia. Twenty-five percent of the sample was white, and 75% was black. One half of the white children and 20% of the black children attended schools in rural areas. The mean sample hematocrit value was 35.7%. Twenty-one percent of the sample had hematocrit values of less than 34.0%. More black children were anemic in both rural and urban groups. Black males had the highest rate of anemia at 27.3%; white females had the lowest rate of anemia at 9.8%. These data show that anemia is a serious problem among children from low-income families and suggest that government nutrition programs such as food stamps and WIC are not meeting the needs of these children. PMID- 8350237 TI - Developmental issues in deaf children. AB - This article presents an overview of the development of deaf children. The central difficulty for these children is acquiring language; however, delays in language development are not inevitable. Deaf children of deaf parents are less likely to experience problems in this and other areas of development than are deaf children of hearing parents, although this latter group represents 90% of the population of deaf children. Much more needs to be known about the development of deaf children and the environmental strategies that maximize the development of children with a major sensory deficit. The implications for caregiving to deaf children and their families are discussed. PMID- 8350238 TI - Values, knowledge, and attitudes about acquired immunodeficiency syndrome in rural adolescents. AB - Adolescents are prone to participate in high-risk behaviors, thus placing themselves at greater risk for human immunodeficiency virus/acquired immunodeficiency syndrome. This study describes knowledge, attitudes, values, health locus of control, and risk-taking potential of 1,048 rural adolescents. The subjects had more correct knowledge than incorrect knowledge about human immunodeficiency virus/acquired immunodeficiency syndrome. The adolescents' personal values of an exciting life and pleasure were related to their likelihood of participating in high-risk behaviors; their attitude score was negatively related to their likelihood of participating in risk behaviors. PMID- 8350239 TI - Pica. PMID- 8350240 TI - Menstrual disorders during adolescence. PMID- 8350241 TI - Knee pain in school-aged girls. PMID- 8350242 TI - Health care reform--the current debate. PMID- 8350243 TI - Fermenter cultivation of intestinal spirochaetes. AB - We cultivated 6 strains of intestinal spirochaetes in a laboratory fermenter under constant conditions (medium, physical-chemical parameters) in a permanent gas flow. It has been possible to demonstrate that the application of the fermenter technique for the cultivation of spirochaetes is a suitable method which can be easily standardized. PMID- 8350244 TI - Taxonomy of lactic acid bacteria from spoiled, vacuum packaged vienna sausages by total soluble protein profiles. AB - To resolve the taxonomic status of sixty-one lactic acid bacteria isolated from spoiled, vacuum packaged vienna sausages, a computer assisted analysis of total soluble protein profiles was undertaken. Sixty-two% of the strains in the study were recovered in fourteen clusters at the 72% similarity level, indicating high degree of heterogeneity among the strains examined. Two clusters representing Leuconostoc species were the largest and most homogeneous, containing twenty strains between them. One cluster contained both typical Lactobacillus sake and Lactobacillus curvatus strains, indicating the inability of protein profiles to consistently differentiate between all strains of these two species. The presence of an independent Lactobacillus curvatus grouping and the clustering of some atypical strains with Lactobacillus sake isolates, however, indicated that the atypical strains may be closely related to Lactobacillus sake. PMID- 8350245 TI - Physical and functional characterization of the cloned lys1+ gene of Schizosaccharomyces pombe. AB - The alpha-aminoadipate pathway for the biosynthesis of lysine is present in yeast and other higher fungi. The lys2 and lys5 mutants of Saccharomyces cerevisiae as well as the lys1- and lys7-mutants of Schizosacharomyces pombe are blocked at the alpha-aminoadipate reductase step of this pathway. The cloned lys1+ gene in the plasmid pLYS1 isolated from a S. pombe genomic library complemented lys1-mutant of S. pombe. The cloned LYS2 gene in the plasmid YEp620 and the LYS5 gene in the plasmid pSC5 of S. cerevisiae exhibited heterologous complementation of lys1- and lys7-mutants, respectively, of S. pombe. The homologous lys1+ transformed cells exhibited five fold higher alpha-aminoadipate reductase activity while the heterologous lys1+ and lys7+ transformed cells exhibited much less activity than the wild type cells. The DNA insert of the plasmid pLYS1 was determined to be 16.7 kb long and the lys1+ gene has been subcloned within a 9.1 kb Clal-Clal DNA insert of the recombinant plasmids pLYS1B and pLYS1C. The restriction pattern for 12 enzymes of the 9.1 kb DNA insert, (Apal, Aval, BamHI, Clal, EcoRI, EcoRV, HindIII, Hpal, Pstl, Pvull, Sphl, and Xbal), exhibited no obvious similarity to that of the LYS2 gene of S. cerevisiae. A 1.7 kb EcoRI-HindIII DNA fragment of pLYS1B and pLYS1C complemented the lys1-131 mutation in an integrative transformation. Although the lys1+ gene of S. pombe is isofunctional to the LYS2 gene of S. cerevisiae, the restriction sites, and expression of these two genes exhibited considerable divergence. PMID- 8350246 TI - Occurrence and characterization of lectins in actinomycetes. AB - 25 species of actinomycetes were tested for the occurrence of lectins. Using a battery of normal and desialized erythrocytes, each species was screened for 3 types of lectin activity i.e. surface bound, extracellular and intracellular. As many as 13 species showed one or more types of activity; some of them were characterized with regard to their biological action spectrum and sugar specificity. PMID- 8350247 TI - Influence of the different amino acid substitutions in Escherichia coli thioredoxin on the growth of bacteriophages T7 and f1. AB - We have constructed three mutants in the thioredoxin (trxA) gene changing its catalytic core between Cys-32 and Cys-35. Oligonucleotide-directed mutagenesis was carried out to replace conservative Gly-33 or Pro-34 by leucine, lysine, glutamine, phenylalanine or tryptophane. The mutants were characterized using an in vivo assay based on the ability of cell (mutants in the chromosomal trxA gene) to support growth of T7 and filamentous f1 phages. The results indicate that the smaller group side-chain in the position 33 and 34 of amino acid residues are indispensable for the growth of phages. PMID- 8350248 TI - Brachymetatarsia. Axial lengthening by using the callus distraction technique. AB - The authors present a modified approach to the ilizarov callus distraction technique for bone lengthening on a patient with brachymetatarsia. This approach has certain advantages and disadvantages that will be discussed along with historical methods of treating brachymetatarsia. The actual case history, surgical technique, and perioperative care of the patient are described in detail. PMID- 8350249 TI - Talonavicular coalition. Objective gait analysis. AB - Talonavicular coalitions, a rarely reported fusion between the talus and navicular, are often an incidental radiographic finding that may be asymptomatic or associated with peroneal spasm. The authors present a review of literature and case report based on clinical evaluation and instrumented gait analysis. Specifically, a patient presenting with a bilateral talonavicular coalition was objectively evaluated with kinetic, kinematic, muscle dynamometry, and pedobarographic testing to understand the biomechanical limitations related to this pathology. An excessive passive component of ankle torque, a high first metatarsophangeal joint plantar pressure, and a diminished time in the midstance portion of stance phase were measured and compared to those of healthy individuals. PMID- 8350250 TI - Efficacy of disinfectants against fungi isolated from skin and nail infections. AB - Commercial disinfectants classified as fungicides may not be effective against commonly encountered fungi within reasonable periods. Cell suspensions of clinical fungal isolates were exposed to use-dilutions of various disinfectants. Quaternary ammonium compounds, iodophors, and phenolics were not fungicidal against all test fungi within 60 min of exposure. Trichophyton mentagrophytes, Epidermophyton floccosum, and Aspergillus fumigatus were among the more resistant fungi. Disinfectants that possess low-level activity should not be used for disinfection of medical instruments that come in contact with the patient. The only reliable and safe measure is to use high-level disinfectants such as the glutaraldehydes, which are fungicidal in 15 to 30 min. PMID- 8350251 TI - Reducing two-dimensional rearfoot motion variability during walking. AB - Although three-dimensional movement analysis is the preferred method of assessing rearfoot motion during gait, the high cost of equipment and the time required to use it often make it unreasonable or impractical in a clinical setting. The authors discuss a method of minimizing the variability of rearfoot motion measurements during walking, using two-dimensional analysis when three dimensional is not available to the clinician. PMID- 8350252 TI - Antimicrobial therapy of skin and soft tissue infection in children. AB - Skin and soft tissue infection and cutaneous abscesses are common in children. They may be polymicrobial in nature, especially when located proximal to mucous membranes. A general knowledge of the common causative bacterial organisms in these infections enables the physician to empirically institute antimicrobial therapy before culture results are available. This review assesses the number and types of aerobic and anaerobic bacteria that occur in skin and soft tissue infections in children. Staphylococcus aureus and Streptococcus pyogenes were recovered from infections occurring at all body sites, but predominated in infections of the leg, neck, and hand. Group D streptococci, Enterobacteriaceae, Neisseria gonorrhoeae, Bacteroides fragilis, and Prevotella species were isolated mostly from infections of the external genitalia and perirectal areas; pigmented Prevotella and Porphyromonas and Haemophilus influenzae can be isolated from infections of the head and neck. Management of skin and soft tissue infections in children should include surgical and medical therapy. PMID- 8350253 TI - Metatarsus proximus and digital divergence. Association with intermetatarsal neuromas. AB - A retrospective radiologic study was performed to determine whether there is an increased finding of metatarsus proximus and digital divergence in patients with a confirmed diagnosis of intermetatarsal neuroma when compared with an asymptomatic group. The study included 48 patients with pathologic confirmation of neuroma and 100 asymptomatic patients. Results of the study revealed no statistical relationship between the radiologic findings of metatarsus proximus and digital divergence and the physical occurrence of neuromas. An unexpected finding was an increased intermetatarsal angle of the affected interspace in the neuroma group. PMID- 8350254 TI - Fibromyalgia. Part I. Review of the literature. AB - Fibromyalgia presents with generalized body pain, multiple tender points, and associated ancillary symptoms, including fatigue and nonrestorative sleep. The abnormal sleep pattern is the most common accepted etiology for this condition. The diagnosis may be made on the basis of a classic presentation of symptoms and clinical findings. The treatment of fibromyalgia includes aerobic exercise and the use of tricyclic antidepressants to modulate the sleep disorder with less than excellent results. In spite of the frustrations in treating this condition successfully, many patients are relieved to be provided with a diagnosis and to obtain sympathetic and supportive care from their physicians. PMID- 8350255 TI - Fibromyalgia. Part II. Prevalence in the podiatric patient population. AB - This study was designed to determine the prevalence of fibromyalgia in the podiatric patient population. A total of 355 consecutive patients in a podiatric outpatient clinic were evaluated to determine whether they met the criteria for this condition. Eight of the 355 patients were diagnosed with the condition. Thirty-five of 355 patients presented with plantar heel or arch pain. Seven of these 35 patients satisfied the criteria for fibromyalgia. This small study indicates that fibromyalgia may be more prevalent in podiatric patients than previously realized and must be considered in patients presenting with foot pain, especially if that pain is in the area of the plantar aspect of the heel or arch. PMID- 8350256 TI - Magnetic resonance imaging of tendon pathology about the foot and ankle. Part I. Achilles tendon. PMID- 8350257 TI - Survey of diabetic patients in a podiatric clinical setting. PMID- 8350258 TI - Alternative treatment for diabetic neuropathic ulcerations. PMID- 8350259 TI - The role of the motor cortex in the control of accuracy of locomotor movements in the cat. AB - 1. The impulse activity of single neurones in the motor cortex (MC) was recorded extracellularly, using movable varnish-insulated tungsten microelectrodes, in six adult, freely moving cats. Neuronal activity was recorded while the cats walked on a flat floor, as they stepped over a series of barriers, and as they walked on the flat rungs of a horizontal ladder. The mean discharge rate (mR) and the depth of frequency modulation (dM) in each cell were estimated over 10-100 steps. 2. The activity of ninety-eight MC cells (Including thirteen pyramidal tract neurones (PTNs)) was recorded during stepping over barriers 25 cm apart. The mR in 66% and the dM in 61% of these cells changed by more than 20% during locomotion with barriers compared to locomotion on the flat (an increase was more often the case). 3. The activity of nine cells was recorded during stepping over barriers 12 cm apart, and the activity of twenty-seven cells (including five PTNs) during walking with barriers only 6 cm apart. The mR in 67% and in 59% of the cells, respectively, and the dM in 56% and in 67% of the cells, respectively, were greater in these locomotor tasks than during locomotion on the flat. 4. The activity of twenty cells was recorded during walking and compared in experiments with different distances between barriers. The mR in 50% and the dM in 75% of the neurones progressively increased when the distance between successive barriers was diminished. 5. The discharge rates of thirteen cells were compared in two different locomotor tasks: (i) when the cat stepped over barriers requiring hyperflexion of the limbs and (ii) when it walked on the flat with loads attached to the distal forelimbs causing a hyperactivity of flexor muscles. The activity of nine cells was different during stepping over the barriers compared to locomotion with loadings on the forelimbs. 6. The activity of 108 cells (twenty four PTNs) was recorded during walking along a horizontal ladder with flat rungs. The mR of 61% and the dM of 72% of cells changed by more than 20% during locomotion on the ladder compared with that on the flat (most often they increased). 7. The position of the peak rate relative to the step cycle did not differ in the majority of cells (in 78-91% depending on the task) during locomotion on the flat, with the barriers or on the ladder.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350260 TI - Spatial facilitation and depression within one motor nerve terminal of frogs. AB - 1. Perfused macropatch electrodes were used to stimulate and simultaneously measure release from two sites on the same terminal of the frog cutaneous pectoris muscle. 2. It was found that release occurring at one site often affected release at an adjacent site 50 microns away, either enhancing it ('spatial facilitation') or depressing it ('spatial depression'). Spatial facilitation (or depression) was defined as the release produced by a test pulse at the second site (test electrode) when preceded by a pulse at the first site (prepulse electrode) divided by the release produced by the test pulse alone. 3. Spatial facilitation varied with the time interval between the prepulse and the test pulse. Peak spatial facilitation, which on the average was 2.14, occurred with an interval of 1-3 ms. With longer intervals spatial facilitation decayed with a time constant between 3-6 ms. When the time interval between the prepulse and the test pulse was zero (no delay), the release after the test pulse was always depressed. 4. When Ca2+ was omitted from the perfusate of the prepulse electrode, spatial facilitation was abolished. When a brief hyperpolarizing pulse followed the depolarizing prepulse with zero delay spatial facilitation was also abolished. 5. Electrotonic spread or Ca2+ diffusion within the axon terminal are excluded as coupling agents for spatial facilitation. It is suggested that the coupling agent may possibly be related to a hypothetical release-promoting factor. PMID- 8350261 TI - Confocal microfluorimetry of Ca2+ signals evoked in Xenopus oocytes by photoreleased inositol trisphosphate. AB - 1. The subcellular characteristics of inositol 1,4,5-trisphosphate (InsP3) induced Ca2+ liberation were studied in Xenopus oocytes by the use of confocal microfluorimetry to monitor Ca2+ signals from minutely localized region of the cell in response to photorelease of InsP3 from a caged precursor. 2. Photorelease of increasing amounts of InsP3 by progressively longer light flashes evoked transient Ca2+ responses that appeared abruptly at a certain threshold duration, and then grew steeply over a narrow range of flash durations to reach a maximum. Further lengthening of flash duration gave no increase in size of the Ca2+ signals, but their rate of rise continued to increase and their duration became longer. Simultaneous measurements of Ca(2+)-activated Cl- currents showed a slightly higher threshold than the Ca2+ signal, and a more graded dependence upon flash duration. 3. The threshold flash durations required to evoke Ca2+ and membrane current signals grew by more than 100-fold as the area of the oocyte exposed to photolysis light was reduced from a square of 140 microns to 5 microns. 4. Ca2+ signals evoked by photoreleased InsP3 began following a dose dependent latency that was as long as several seconds with low intensity light, but shortened to about 50 ms at maximum intensity. The extrapolated minimum latency with infinite photorelease of InsP3 was about 30 ms. 5. InsP3-evoked membrane currents began 30 ms or longer after the corresponding Ca2+ signals, whereas currents evoked by photorelease of Ca2+ from a caged precursor began within 5 ms of the onset of the light flash. 6. No differences in duration of InsP3-evoked Ca2+ signals were apparent when the confocal measuring spot was positioned close to the plasma membrane or about 10 microns more deeply into the oocyte. At both locations the Ca2+ signals were more prolonged than the associated membrane current signals. 7. Ca2+ signals to a test light flash were suppressed for about 2 s following a conditioning suprathreshold flash, but recovered almost completely after 6 s. The associated membrane current signals were facilitated at short intervals, suppressed at intervals between 0.5 and 3 s, and subsequently recovered more slowly than the Ca2+ signals. 8. Photorelease of InsP3 during 30 s exposures of low intensity evoked trains of repetitive Ca2+ spikes. The overall amplitudes of these responses changed little with increasing in frequency, and became smaller and superimposed on a more sustained elevation of Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350262 TI - Modulation of respiratory activity of neonatal rat phrenic motoneurones by serotonin. AB - 1. The effects of serotonin on phrenic motoneurones were studied in an in vitro preparation of the isolated brainstem and spinal cord from neonatal rats. 2. Serotonin (5-HT; > or = 5-10 microM) increased inspiratory-modulated phrenic nerve activity and produced a small amount of tonic activity during expiration. Inspiratory-modulated activity of the fourth cervical ventral root also increased, but was accompanied by robust tonic activity, which often obscured the rhythmic activity. 3. Serotonin, in both normal and tetrodotoxin-containing medium, depolarized phrenic motoneurones and increased cell input resistance. Serotonin also increased inspriatory-modulated firing as well as the response of phrenic motoneurones to injected current. The y-intercept of the relationship between firing frequency and injected current (f-I) was increased, but the slope was not affected. There was no bistable firing behaviour. 4. Under voltage clamp conditions, 5-HT produced a tonic inward current of 0.07-0.37 nA. This current increased with less negative holding potentials and decreased with more negative holding potentials (-75 to -90 mV) but did not reverse. 5. In addition, 5-HT decreased inspiratory-modulated synaptic current by 23 +/- 6%. The degree of attenuation was not affected by holding potential. The time course of the decrease in inspiratory-modulated synaptic current was similar to the changes seen in tonic inward current and input resistance. 6. Depolarization, tonic inward current, and shift in the f-I relationship produced by 5-HT were antagonized by the 5-HT2/1C receptor antagonist ketanserin and mimicked by the 5 HT2/1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). However, the 5-HT induced decrease in inspiratory-modulated synaptic current was not reduced by ketanserin nor mimicked by DOI. 7. We conclude that exogenously applied 5-HT simultaneously increases cell excitability and decreases inspiratory modulated synaptic current in phrenic motoneurones via different types of receptors. When these responses occurred simultaneously, the increase in excitability predominated and the net effect was an augmentation of inspiratory modulated phrenic motoneurone activity. PMID- 8350263 TI - Spatial integration and sensitivity changes in the human rod visual system. AB - 1. The factor by which increment threshold rises with increasing background intensity is less if the target is small than if it is large. The difference is usually attributed to a reduction in the area over which visual signals are integrated as the visual system light adapts. Recently, however, it has been argued that the difference in slope may instead be caused by an increase in the gain of the local response function with light adaptation. 2. To test this hypothesis in the rod-driven visual system, we compared monoptic, small and large target increment thresholds, and dichoptic, large target brightness matches, measured as a function of background intensity in a typical, complete achromat, who has no cone vision. 3. The dichoptic brightness matches were made using a large target of a similar intensity to the threshold intensity of the small target. If local intensity is important, the large target brightness matching curve should be more similar to the shallow, small target threshold curve. But, if changes in spatial integration are important, the brightness matching curve should be similar to the steeper, large target threshold curve. 4. The slope of the large (1.85 deg) target increment threshold functions measured with either 200 or 50 ms test flashes were steeper than those of the small (10 min of arc) target functions by 0.10 (on logarithmic co-ordinates) or about 15%. 5. The logarithmic slopes of the dichoptic brightness curves were also slightly steeper than the small target increment functions. This is contrary to the local response (only) hypothesis, which predicts that the brightness curve should have the same slope as the small target function because the luminance of the targets in the two cases is the same. 6. We conclude that there must be a change in spatial integration in the rod visual system during light adaptation, over and above that due to local gain changes. PMID- 8350264 TI - Long-term changes in synaptic strength along specific intrinsic pathways in the cat visual cortex. AB - 1. The dense system of horizontal connections that arise and course within the striate cortex are thought to inform single cells about stimuli arising in disparate points in visual space and to modulate responses evoked from within the receptive field. To learn whether or not the strength of the horizontal connections could vary over the long term, and if such changes could affect the integration of vertical, interlaminar inputs, we have recorded intracellularly from the superficial layers in slices of the adult cat's visual cortex. 2. The monosynaptic EPSP evoked by stimulating horizontal fibres showed long-term facilitation in twelve of the twenty cells that were conditioned by repetitively pairing synaptic responses with depolarizing pulses of current; the maximum increase observed was 200%. Strong inhibition present in the postsynaptic response usually indicated that facilitation would not occur. 3. In instances where horizontal input evoked both mono- and polysynaptic EPSPs, both early and late events showed facilitation, with the most dramatic enhancement contributed by the polysynaptic components. 4. For the twenty-eight cells whose responses to stimulation of interlaminar as well as horizontal pathways were assessed, all were found to receive non-overlapping inputs from each source. Conditioning produced long-term changes in the strength of the interlaminar inputs. 5. Changes in synaptic strength were usually confined to the conditioned pathway, though in four out of twenty-six times we observed heterosynaptic facilitation of polysynaptic EPSPs. 6. The conditioning protocol led to lasting depression rather than facilitation in three out of eleven instances; the reduction was only observed in the multisynaptic components. 7. We suggest that the synaptic changes observed here may be related to certain dynamic changes in receptive field properties that have been characterized in vivo. PMID- 8350265 TI - Activation of muscarinic K+ current in guinea-pig atrial myocytes by a serum factor. AB - 1. Atrial myocytes obtained by enzymatic perfusion of hearts from adult guinea pigs and cultured for 0-14 days were studied using the whole-cell voltage-clamp technique. 2. Superfusion of the myocytes with diluted sera (1:100 to 1:10,000) from different species (human, horse, guinea-pig) evoked an inward rectifying K+ current. The voltage-dependent properties of this current were identical to those of the K+ current activated by acetylcholine (IK(ACh)). Current density in the presence of horse serum (1:100) approximately corresponded to the non desensitizing fraction of IK(ACh) during superfusion with 1-2 x 10(-6) M ACh. 3. During a maximal serum-evoked current, application of ACh (10(-6) M) failed to evoke additional K+ current. After switching superfusion from serum-containing to serum-free solution, the K+ current decayed 1-2 orders of magnitude slower than ACh-activated IK(ACh). During the decay of the serum-evoked current, a proportional increase in responsiveness to ACh was recorded. During submaximal activation of K+ current by serum, a saturating concentration of ACh resulted in a total current that was identical to the current evoked by ACh alone minus the desensitizing component. Thus, activation of K+ current by serum caused desensitization of IK(ACh). From these results it is concluded that sera contain a factor that activates the same population of K+ channels as ACh. 4. Irreversible activation of IK(ACh) by ACh in myocytes dialysed with the GTP analogue GTP-gamma-S abolished sensitivity to serum and vice versa. 5. The effect of serum was not modified by atropine (10(-6) M) which completely blocked the response to 2 x 10(-6) M ACh. Furthermore, theophylline (1 mM), which completely inhibited IK(ACh) activation by adenosine (100 microM), failed to inhibit the effect of serum. Thus, neither muscarinic nor purinergic (A1) receptors are involved. 6. The peptide somatostatin (10(-6) M) and the alpha 1-agonist phenylephrine (1 microM) which previously have been shown to cause activation of IK(ACh) channels, in the present study failed to evoke any measurable current, which excludes the involvement of the corresponding receptors. 7. Pre-incubation of the cells with pertussis toxin completely abolished IK(ACh) evoked by ACh, adenosine and serum, suggesting that the activating factor, like the classical agonists, causes opening of IK(ACh) channels via a G protein (Gi, GK). 8. The potency of serum to activate IK(ACh) was not reduced by dialysis, suggesting the molecular mass of the unknown factor to be > or = 5 kDa. No activating potency was found in the dialysing solutions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350266 TI - The role of the motor cortex in the control of vigour of locomotor movements in the cat. AB - 1. The impulse activity of single neurones in the motor cortex (MC) was recorded extracellularly using movable varnish-insulated tungsten microelectrodes in four adult freely moving cats. The cats walked inside the experimental box with various loadings in the swing or stance phases of the step cycle. The mean discharge rate (mR) and the depth of frequency modulation (dM) in each neurone were estimated over 10-100 steps. 2. The activity of thirty-one cells (including eighteen pyramidal tract neurones (PTNs)) was recorded during uphill walking on a 10 deg inclined floor. The mR in 68%, and the dM in 77% of neurones changed by less than 20% during uphill locomotion compared to walking on a level surface. 3. The activity of the same neurones was also recorded during downhill walking, also on a 10 deg inclined plane. The mR in 69% and the dM in 78% of neurones changed by less than 20% during downhill locomotion compared with walking on a level surface. 4. The activity of twenty-three (the left hemisphere) cells (sixteen PTNs) during walking with the floor swaying to the right (R) and to the left (L) was compared to activity during locomotion on a stable surface. The mR in 83% and the dM in 83% of cells in R-steps, and in 82 and 77% of cells, respectively, in L steps changed by less than 20%. 5. The activity of thirty-seven cells was studied during locomotion at various speeds. The mR in 68% and the dM in 38% of cells changed by less than 20% during fast and slow locomotion compared to middle-speed locomotion. The dM in 46% of neurones increased with the transfer from slow to fast walking. 6. The activity of thirty-one MC cells was recorded during locomotion with loads of 85 g attached to the distal part of each elbow. The mR in 52% and the dM in 48% of neurones changed by more than 20%. 7. The activity of twenty-eight cells (six PTNs) was studied in steps when an animal turned. The swing of the limb contralateral to the recorded MC was shorter (condition 1) in turning steps in one direction, and was longer (condition 2) in turning steps in the opposite direction. The mR in 50% and the dM in 50% of cells in condition 1 and in 52% and 59%, respectively, of cells in condition 2 changed by more than 20%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350267 TI - Inter-individual variability in the dynamics of natural accommodation in humans: relation to age and refractive errors. AB - 1. To study the relationship between accommodation under natural viewing conditions, age and refractive errors, we have measured time courses of accommodation in thirty-nine human subjects aged 5-49 years using a newly developed technique. The technique is based on infrared photoretinoscopy and involves fully automated on-line image processing of digitized video images of the eyes with a sampling rate of 5.3 Hz. 2. The distance between the subject and the video camera was about 1.3 m. Head movements of the subject required little restriction because the eyes were automatically tracked in the video image by the computer program. All subjects were tested under binocular viewing conditions. 3. Both refraction of the right eye and pupil diameter were measured with a precision of 0.2-0.4 dioptres (D) and 0.1 mm, respectively, and were plotted on line. The data were subsequently automatically analysed. 4. Automated infrared photoretinoscopy proved to be very convenient and easy to handle in both children and adults. 5. The maximal speed of accommodation for a target at a distance of 5 D declined in the subjects with age (from up to 21.7 D s-1 for accommodation and 32.7 D s-1 for subsequent accommodation to a distant target ('near to far accommodation') in children down to 2-18 D s-1 in adults). There was a striking inter-individual variability in the maximum possible speed of accommodation and near to far accommodation. 6. Speed of accommodation and of near to far accommodation was correlated for each subject. However, in most of the subjects, the process of near to far accommodation was faster than accommodation (P < 0.005, if averaged over all subjects). This correlation was independent of age. 7. The accommodation-induced pupillary constriction (pupillary near response) was absent in children for a 4 D target; even at 10 D, there was no reliable pupillary response. The pupillary near response increased to about 1.6 mm D-1 of accommodation at the age of 47. Since a pupillary near response could still be elicited in presbyopic subjects unable to accommodate, the ratio of pupillary constriction per dioptre of accommodation approached infinity. 8. The magnitude of the pupillary near response was highly variable even among subjects of the same age but was typical for each subject. There was a correlation (P < 0.01) to refractive error: corrected myopes had weaker pupillary near responses than emmetropes or hyperopes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350268 TI - Phase-dependent dynamic responses of respiratory motor activities following perturbation of the cycle in the cat. AB - 1. Electroneurographical (ENG) activities of a phrenic nerve, a thyroarytenoid (TA) branch of a recurrent laryngeal nerve, and a triangularis sterni (TS) branch of an internal intercostal nerve were recorded in decerebrate, vagotomized and paralysed cats. A superior laryngeal nerve (SLN) was stimulated electrically. Our objective was to evaluate transient changes in motor activity following a brief perturbation of the respiratory cycle by SLN stimulation. 2. Each motor nerve recorded represents a separate phase of the respiratory cycle. We measured the duration of phrenic ENG activity for inspiratory phase duration (TI) and similarly the duration of TA and TS ENG activity for the duration of stages I and II of expiration, respectively. Changes in the duration of the total respiratory cycle (TTOT) were also measured. Therefore, the changes in TTOT were accounted for directly by changes in each phase of the respiratory cycle. 3. Perturbation during the inspiratory phase inhibited phrenic activity either reversibly or irreversibly (premature termination of inspiration) depending on the strength and timing of the stimulus. Reversible inhibition of inspiration was associated with a transient activation (< 100 ms) of the TA nerve followed by a reactivation of the phrenic nerve, but the duration of the subsequent stages I and II of expiration remained the same. Thus, the prolongation of TTOT was completely accounted for by the lengthening of TI. 4. Premature termination of inspiration was followed by either a shortening (the first half of inspiration) or a lengthening (the second half of inspiration) of the duration of stage I expiration and consistently by a shortening of the duration of stage II expiration. The magnitude of these changes in the durations of stages I and II of expiration was phase dependent. Changes in the duration of all three phases of motor activity contributed to the changes in TTOT. 5. Perturbation during stage I expiration prolonged this stage but did not affect the duration of the succeeding stage (stage II expiration). The increase in the duration of stage I expiration appeared constant and not dependent on the time when the perturbation was delivered in stage I expiration. Thus, the change in TTOT was less phase dependent during stage I expiration than during inspiration and stage II expiration and was accounted for by changes in the duration of TA activity alone. 6. Perturbation during stage II expiration inhibited TS activity and evoked TA activity transiently.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350269 TI - A statistical analysis of acetylcholine receptor activation in Xenopus myocytes: stepwise versus concerted models of gating. AB - 1. The kinetic properties of single channel currents from fetal-type acetylcholine receptors in embryonic Xenopus myocytes (60 h old) have been analysed by a maximum-likelihood method. 2. At very high acetylcholine (ACh) concentrations (up to 5 mM) the effective opening rate appears to saturate at approximately 30,000 s-1. 3. The kinetics were analysed according to the standard concerted scheme that postulates a single channel-opening conformational change after two agonists are bound, and a rarely invoked stepwise scheme that postulates semi-independent conformational changes in two distinct gating domains. Both models assume that agonist cannot escape from a channel (or domain) that is in its activated conformation. 4. With either activation scheme the kinetic analyses indicate that ACh binds at a rate of approximately 2 x 10(8) s-1 M-1 and dissociates from doubly liganded receptors at a rate of approximately 28,000 s-1, and that the activation process is asymmetric, i.e. the binding (concerted model) or gating (stepwise model) transitions are not equal and independent. 5. In eighteen of twenty-seven file-by-file comparisons, the likelihood of the stepwise model was greater than that of the concerted model. In seven such comparisons, the likelihood of the concerted model was greater than that of the stepwise model, and in two there was no difference. Log likelihood ratio distributions were obtained from three files (those with the most events) by multiple cycles of resampling and fitting. The means of these distributions were significantly greater than zero, indicating that the stepwise scheme was as good as, or better than, the concerted scheme in describing receptor activation. 6. According to the stepwise view, two binding sites must be occupied and two 'gates' activated for conduction to occur. Although equivalent binding is not an essential aspect of stepwise activation, the binding sites can be identical and have a low affinity for ACh (Kd approximately 130 microM). Either the isomerization rates of the gating domains are different, or they are influenced by the conformational status of its counterpart, with activation increasing approximately 3-fold and deactivation decreasing approximately 10-fold if the complementary domain is in the active conformation. Stepwise activation predicts that the decay of the endplate current is determined by five rates. PMID- 8350270 TI - Responses to sympathetic nerve stimulation of the sinus venosus of the toad. AB - 1. The changes in membrane potential produced by sympathetic nerve stimulation were recorded from sinus venosus preparations of the toad, Bufo marinus, in which beating had been prevented by the dihydropyridine calcium antagonist, nifedipine. 2. Supramaximal sympathetic stimuli initiated long-lasting excitatory junction potentials which started with the same latencies, some 1 to 2 s, as did sympathetic tachycardias recorded from beating preparations. 3. Brief trains of stimuli increased the amplitude of excitatory junction potentials and shortened their latency of onset. Similarly when excitatory junction potentials were facilitated their latency of onset was shortened. 4. The time courses of excitatory junction potentials were prolonged by cooling the preparation but unchanged when the neuronal uptake of catecholamines was inhibited. 5. In arrested preparations, beta-adrenoceptor activation causes a hyperpolarization, as did the inhibition of phosphodiesterases or the activation of adenylate cyclase. This contrasts with the depolarization produced by sympathetic nerve stimulation which could be mimicked by the rapid application of either adrenaline or noradrenaline but not by beta-adrenoceptor activation, phosphodiesterase inhibition or by adenylate cyclase activation. 6. The results are discussed in relation to the idea that neuronally released adrenaline activates a set of adrenoceptors which are linked to a set of channels by a pathway that does not involve cyclic AMP. PMID- 8350271 TI - Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. AB - 1. We studied the effects of acute isocapnic hypoxia on arterial and central venous pressures, carotid and femoral blood flows and heart rate in intact and carotid denervated fetal sheep between 118 and 125 days gestation, after pre treatment with either saline, atropine or phentolamine. Electrocortical activity (ECoG) and the incidence of fetal breathing movements (FBM) were also compared between intact and carotid denervated fetuses. 2. There were no significant differences between intact and denervated fetuses in any variable measured during normoxia. Soon after the onset of hypoxia a marked bradycardia occurred in intact, but not in denervated fetuses. Femoral blood flow and femoral vascular resistance (perfusion pressure/femoral blood flow) increased in intact, but not in denervated fetuses. Carotid blood flow increased in both groups of fetuses during hypoxia, but carotid vascular resistance did not change. During hypoxia, the incidence of FBM and low-voltage ECoG was similarly reduced in both groups of fetuses. 3. Atropine produced a rise in fetal heart rate during the control period in intact but not in denervated fetuses. At the onset of hypoxia atropine prevented the initial bradycardia seen in intact fetuses. In denervated fetuses a further increase in heart rate occurred throughout the hypoxia. 4. All denervated fetuses treated with phentolamine died during the hypoxic challenge, but nine out of fourteen intact fetuses treated with phentolamine survived. 5. In intact fetuses which survived hypoxia after treatment with phentolamine, the increase in arterial blood pressure was smaller and the increase in femoral resistance did not occur. In these fetuses a rise in heart rate occurred in hypoxia. Carotid vascular resistance decreased during hypoxia after administration of phentolamine. 6. Our results indicate that the initial cardiovascular responses of the late gestation sheep fetus to hypoxia are reflex, and that the carotid chemoreceptors provide the afferent limb of this reflex. The bradycardia is mediated through a muscarinic pathway, as it is blocked by atropine. The femoral vasoconstriction is mediated through an alpha-adrenergic mechanism, mediated both neurally by a carotid chemoreflex and via catecholamines released directly from the adrenal medulla. Both these components are blocked by phentolamine. 7. The differences in survival between intact and denervated fetuses during hypoxia after phentolamine suggest that the carotid chemoreflex response to hypoxia involves mechanisms in addition to vagal efferents to the heart and alpha adrenergic actions at peripheral blood vessels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350272 TI - Metabolic acidosis and breathlessness during exercise and hypercapnia in man. AB - 1. A previous study showed that when combined with exercise in normal subjects, hypercapnic and hypoxic ventilatory stimuli did not have a specific effect on the intensity of the sensation of breathlessness in addition to their stimulation of ventilation. The aim of the present study was to assess the significance of another reflex ventilatory stimulus, metabolic acidosis, in the genesis of this sensation. 2. Six subjects performed progressive exercise tests (mean workload, 103 W; range, 88-125 W) with normal acid-base status. Following NH4Cl-induced metabolic acidosis (mean change in base excess, -3.6 mmol l-1; range, -0.3 to 6.8 mmol l-1) exercise was repeated (mean workload, 91 W; range, 53-116 W) such that the combined ventilatory stimulation resulted in levels of ventilation (mean maximum, 65 l min-1) 'matched' to those resulting from exercise alone. A third, 'matched ventilation', exercise test was performed during metabolic acidosis but with end-tidal PCO2 controlled to a normal level (mean workload, 56 W; range, 17 103 W). Breathlessness was assessed using a visual analogue scale (VAS). 3. Progressive hypercapnic ventilatory stimulation was given before (mean maximum end-tidal PCO2 (PET,CO2), 61 mmHg) and during metabolic acidosis (mean maximum PET,CO2, 57 mmHg) to achieve the same peak level of ventilation (mean maximum, 59 l min-1). Breathlessness was assessed with the VAS. 4. As ventilation increased during a test, there were no statistically significant differences in the increasing breathlessness scores with metabolic acidosis compared to control, for either exercise (mean VAS, 22 mm vs. 24 mm) or progressive hypercapnia (mean peak VAS, 31 mm vs. 32 mm). 5. These results do not support the idea that metabolic acidosis is associated with a change in the relationship between the intensity of breathlessness and ventilation; this is similar to results found with other reflex ventilatory stimuli. 6. These findings are consistent with the hypothesis that the degree of reflex ventilatory activation is an important determinant of the intensity of the sensation of breathlessness in healthy humans, irrespective of the exact nature of ventilatory stimulus. PMID- 8350273 TI - Effect of endothelin-3 on vasopressin release in vitro and water excretion in vivo in Long-Evans rats. AB - 1. The endothlins (ETs) are a family of homologous peptides originally isolated and purified from cultured porcine endothelial cells. Although initial studies focused on the ETs as potent vasoconstrictor substances, recent findings support a role for ET in vasopressin (AVP) secretion and action. We used cultured explants of the hypothalamo-neurohypophysial complex (HNC) to examine the effects of ET-3 on AVP release. 2. ET-3 produced a significant and concentration dependent rise in AVP release from the explants of Long-Evans rats at 48 h, independent of medium osmolality. AVP release during two sequential control periods did not differ, and osmotically stimulated AVP release was comparable to that exhibited by HNC explants from Sprague-Dawley rats. ET-3 (1 nM) induced a 3 fold rise in AVP that was completely blocked by rabbit antiET serum, which did not alter basal AVP secretion. 3. Clearance experiments were performed in anaesthetized water-loaded rats given a non-pressor dose of ET-3 (0.40 nmol (kg body weight)-1 intravenously). The means of body weight, arterial blood pressure, plasma Na+ concentrations, and plasma osmolalities did not differ between the first and second periods nor among the groups. Despite no changes in renal plasma flow and inulin clearance, free water clearance significantly increased in the ET treated group. This response could not be attributed to changes in osmolal clearances or Na+ reabsorption. The concurrent administration of antiET serum not only blocked this effect, but was associated with the free water clearance falling significantly below the pretreatment level. 4. Taken together, our in vivo and in vitro findings support the hypothesis that ET-3 stimulates AVP secretion. Furthermore, our data are consistent with the site of action of ET-3 residing within the blood-brain barrier, though an independent effect by a higher concentration of ET at neural loci outside the barrier cannot be totally excluded. Finally, the subpressor dose of ET-3 amplifies free water excretion independent of systemic and renal haemodynamics, Na+ excretion, osmolal clearance, or circulating AVP levels. PMID- 8350275 TI - Changes in contractile properties by androgen hormones in sexually dimorphic muscles of male frogs (Xenopus laevis). AB - 1. Male frogs (Xenopus laevis) were castrated then given either empty or testosterone-filled implants to produce animals with low or high levels of circulating testosterone. Eight weeks later the contractile properties of an androgen-sensitive forelimb flexor, the flexor carpi radialis muscle (FCR), were measured in vitro. Another forelimb flexor muscle, the coracoradialis, and a hindlimb muscle, the iliofibularis, were analysed similarly. 2. Plasma testosterone levels were 0.9 +/- 0.3 ng/ml (+/- S.E.M.) in castrated frogs with blank implants (C) and 61.3 +/- 4.7 ng/ml in castrates with testosterone implants (CT). Unoperated males, sampled at various times of the year, ranged between 10.8 and 51.0 ng/ml. 3. With direct electrical stimulation of the FCR, contraction time of the isometric twitch was not affected by testosterone levels. Relaxation times were affected, however. Half- and 90% relaxation times were 27 and 42% longer, respectively, for CT compared to C muscles. 4. Testosterone also had no effect on the contraction time of twitches elicited by stimulation of the FCR nerve. Half- and 90% relaxation times were 51 and 76% longer, respectively, for CT compared to C muscles. 5. Tetanus tension, elicited by direct stimulation of the FCR at 50 Hz, was 86% greater in CT compared to C muscles. The average cross sectional area of FCR muscle fibres was 84% greater in CT muscles. These results implied that testosterone treatment had no effect on specific muscle tension. 6. Stimulation of the FCR nerve at 50 Hz resulted in 53% less tension than the same stimulus applied directly to CT muscles. In C muscles the difference was only 14%. This suggested that testosterone treatment reduced synaptic efficacy. 7. In CT muscles, direct or nerve stimulation of fibres in the shoulder region of the FCR elicited twitches that contracted and relaxed more slowly than fibres in the elbow region. In C muscles there was no difference in contraction or relaxation time between fibres in the shoulder and elbow regions. 8. Testosterone treatment had little effect on contraction and relaxation times or tension levels of coracoradialis or iliofibularis muscles. PMID- 8350274 TI - Synaptic and intrinsic conductances shape picrotoxin-induced synchronized after discharges in the guinea-pig hippocampal slice. AB - 1. A computer model was constructed of the guinea-pig hippocampal region in vitro, containing 100 pyramidal neurones. This approach has contributed to the understanding of brief (usually less than 100 ms) epileptic events known as 'interictal spikes'. The present study addresses the cellular mechanisms of more prolonged epileptic events, lasting 200 ms and more, that may represent short duration seizures. Each neurone was simulated with a nineteen-compartment model using six voltage-dependent ionic conductances. The neurones were randomly interconnected with excitatory synapses, each synapse exerting a fast voltage independent alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) component and a slower voltage-dependent N-methyl-D-aspartate (NMDA) component. Each neurone received input from twenty other neurones. 2. This model was able to generate, in response to synaptic noise or to stimulation of one neurone, a series of synchronized population bursts, the initial (primary) burst being longer than later (secondary) bursts, terminating in a prolonged after hyperpolarization. The simulated after-discharge potentials resemble those recorded experimentally from pyramidal neurones during perfusion of the hippocampal slice with media containing picrotoxin, a blocker of synaptic inhibition mediated by GABAA receptors. 3. Simulated after-discharges agree with the following experiments: over a certain range of total NMDA conductance, blockade of AMPA receptors will prevent the occurrence of synchronized firing, whereas, blockade of NMDA receptors will, in contrast, abolish the secondary bursts, leaving a shortened and somewhat smaller primary burst. Dendritic potential oscillations occur in phase with somatic oscillations. When interneurones (some generating GABAA-mediated IPSPs, others generating GABAB IPSPS) are included in the model, the occurrence of synchronized events was suppressed, the most significant suppressant effect coming from GABAA IPSPS. 4. The model predicts that: a dendritic calcium spike occurs during each secondary burst; AMPA receptors serve to maintain the synchrony of secondary bursts, as well as to initiate the primary burst; and that with sufficient total NMDA conductance, synchronized firing can occur even with AMPA receptors blocked. 5. The model suggests, in addition, that the duration of the initial burst is determined in part by the experimentally observed delay between Ca2+ entry and peaking of the after-hyperpolarization (AHP) conductance, and hence reflects properties of the individual pyramidal neurones. Specifically, a pattern of a long initial burst followed by brief secondary bursts is elicited in single-cell simulations by injection of a steady depolarizing current into the apical dendrite. The same pattern is produced when the single-cell model includes only calcium and calcium-dependent conductances.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350276 TI - Permeability of disrupted cerebral microvessels in the frog. AB - 1. This study reports the results of varying the hydrostatic pressure on measurements of permeability coefficient to the low molecular weight impermeant dye carboxyfluorescein (MW = 376) in single leaky cerebral microvessels. A mathematical model, that solved the convective diffusion equations used to analyse the measurements, showed that the measurements were consistent with leakiness being due to 22 nm wide parallel-sided slits between endothelial cells. 2. Microvessels on the surface of the frog's brain were cannulated with a micropipette and perfused with an artificial cerebrospinal fluid containing the dye. Vessels were occluded with a glass microneedle and the rate of change in dye concentration in a 12 microns length section was measured using video-intensified microscopy. 3. It was found that the rate of dye loss at all points along the occluded microvessel segment could be accounted for by a model for convection and diffusion, and that changes in dye concentration at a point remote from the segment entrance can give a good measure of diffusive permeability. 4. When series of measurements were carried out on a single vessel, permeability rose over the course of 20 min. Mean permeability for all measurements was 3.01 x 10( 5) cm sec-1, n = 64 (mode, 2.0; range, 0.48-9.6). The hydrostatic pressure applied during the perfusion had no effect on the measured permeability. 5. The dye concentration along the vessel axis was measured at the steady state and was shown to respond to changes in hydrostatic perfusion pressure in a way predicted by the model. This indicates that hydrostatically driven bulk flow can be important, and thus convection may account for effects previously ascribed to vesicular transcytosis. 6. The possible anatomical basis for the porous pathway is discussed in the light of recent observations on the presence of 0.5 microns perijunctional gaps, the possibility of transendothelial channels, and the unzipping of tight junctions to leave a 22 nm wide slit. PMID- 8350277 TI - Calcium accumulation by organelles within Myxicola axoplasm. AB - 1. 45Ca2+ accumulation into inulin-inaccessible compartments within cytoplasm from the giant axon of Myxicola infundibulum was measured as a function of free calcium, pH, and time. Accumulation reached a maximum after 1 h and remained stable for at least 3 h. 2. At 0.5, 5, and 50 microM [Ca2+], in the presence of 1 mM ATP or 5 mM succinate, steady-state calcium uptake had a bell-shaped dependence on pH with a maximum near pH 7. Uptake was abolished by the proton uncoupling reagent carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP, 4 micrograms ml-1). 3. Uptake of the membrane permeant cation, [14C] tetraphenylphosphonium (TPP+), also had a bell-shaped dependence on pH with a maximum pH approximately 7, suggesting a pH dependence of the electrical potential of a membrane enclosed cytoplasmic compartment. Cyanide (2 mM) inhibited TPP+ uptake. 4. Inositol 1,4,5-trisphosphate (IP3, 10 microM), reduced steady-state calcium accumulation by 20-22% at 0.5 microM free calcium, pH 7 (P < 0.01, n = 16) and at 5 microM free calcium, pH 8 (P < 0.0005, n = 35). No effects of IP3 were found at other pH or calcium concentrations. 5. Neither guanosine 5' triphosphate (GTP) nor inositol 1,3,4,5-tetrakisphosphate (IP4) had an effect on calcium uptake (5 microM [Ca2+], pH 8). 6. At 0.5 microM free calcium; vanadate (10 microM) inhibited 20-30%, of the 45Ca2+ accumulation, thapsigargin (33 nM) inhibited 20-30%, and cyanide (2 mM) plus oligomycin B (2 micrograms ml-1), or valinomycin (1 microM), inhibited 70-80%. The fraction of uptake sensitive to thapsigargin fell as the free calcium increased; however, the sensitivity of uptake to cyanide plus oligomycin B was approximately 80% for 0.5, 5.0, and 50 microM [Ca2+]. 7. Thapsigargin had no additional inhibiting effect in the presence of cyanide plus oligomycin B. IP3 had no effect in the presence of cyanide plus oligomycin B or other mitochondrial inhibitors. 8. Results suggest the presence of both mitochondrial (70-80%) and non-mitochondrial (20-30%) calcium pools in this system (at 0.5-5.0 microM Ca2+). The apparent non mitochondrial uptake (sensitive to thapsigargin, or IP3) is not detectable in the presence of mitochondrial inhibitors. We interpret these results as evidence of functional communication between mitochondrial and non-mitochondrial calcium stores. PMID- 8350278 TI - Contralateral projections of thoracic respiratory interneurones in the cat. AB - 1. Retrograde neuronal transport following small iontophoretic injections of horseradish peroxidase was used to investigate the location of neurones projecting to the thoracic ventral horn of the cat. 2. A concentration of labelled neurones was seen in the contralateral medial ventral horn at the immediately opposite rostrocaudal position. 3. The participation of respiratory interneurones in the projection was investigated by means of spike-triggered averaging, as follows. 4. Spike trains of single interneurones whose firing patterns were related to the central respiratory cycle were recorded extracellularly in the thoracic ventral horn of anaesthetized, paralysed cats. Firing patterns were defined by the construction of cycle-triggered histograms. 5. Spike-triggered averaging of the signal from an extracellular tungsten microelectrode in the opposite ventral horn was performed to test for the presence of axonal, terminal or focal synaptic potentials. 6. At least one of these types of potential was found for 34/55 units. Terminal potentials were found for thirty-one units, accompanied by focal synaptic potentials for twenty seven units. Potentials were found for units with all types of firing patterns. Units whose activity elicited these potentials were generally located in the medial half of the ventral horn. 7. We conclude that at least 60% of the respiratory interneurones project to the immediately opposite ventral horn. PMID- 8350279 TI - Functional identities of thoracic respiratory interneurones in the cat. AB - 1. Spike-triggered averaging was used to reveal focal synaptic potentials (FSPs) in the thoracic ventral horn resulting from impulses in individual respiratory interneurones situated in the contralateral ventral horn of the same segment (T6 or T7) in anaesthetized paralysed cats. 2. FSPs were of two types, negative-going or positive-going, and were of the same sign at each of several sites for each unit. These two types were interpreted as indicating excitatory or inhibitory actions respectively. 3. The positive-going FSPs were almost all the result of activity in the most strongly modulated, phasic respiratory interneurones, whereas most of the negative-going ones were derived from neurones with a continuous tonic component in their firing patterns. 4. Positive-going FSPs (particularly those from inspiratory neurones) were generally found at more ventral sites in the ventral horn than negative-going ones. 5. It is suggested that an important role for the phasically active interneurones is to provide phasic inhibition, which is combined with largely tonic excitation to produce strong respiratory modulation in the activity of other neurones in the thoracic spinal cord, particularly in motoneurones. However, some groups of respiratory interneurones, such as a group of tonic inspiratory ones which are located more dorsally than the phasic inspiratory ones, may not receive such phasic inhibition. PMID- 8350281 TI - The effect of endotoxin-induced fever on thermoregulation in the newborn rabbit. AB - 1. Metabolic responses of endotoxin-injected newborn rabbits were measured in a closed circuit calorimeter at a constant environmental temperature within their thermoneutral range. Oxygen consumption and colonic temperatures were then measured over a range of environmental temperatures from 21.0 to 40.0 degrees C and the responses of endotoxin-injected rabbits compared with non-injected litter mates. 2. To measure their preferred thermal environment, endotoxin-injected and non-injected litter mates were allowed to settle on a thermal gradient and their colonic temperatures measured. 3. In a constant environmental temperature of 37 degrees C, rises in oxygen consumption and colonic temperature following endotoxin injection were found to be biphasic. Oxygen consumption rose from 21 ml kg-1 min-1 to a maximum 35 ml kg-1 min-1 and colonic temperature rose from 39.0 to 39.8 degrees C. 4. The maximal rate of oxygen consumption was the same in both injected and non-injected animals, 53 ml kg-1 min-1, being provoked at the same environmental temperature of 24 degrees C. Minimal rates of oxygen consumption were also similar for the two groups but in the injected animals they were achieved at an environmental temperature of 39 degrees C, 2 degrees C higher than for non-injected animals. 5. We conclude that newborn rabbits challenged with a pyrogen have both behavioural and physiological responses. The thermogenic response is consistent with a change in sensitivity to feedback information rather than a simple shift in the central thermoregulatory set point. We find no evidence to support the view that in the febrile response a higher body temperature necessitates an increase in metabolic rate, the so-called Q10 effect. PMID- 8350280 TI - Agonist-independent effects of muscarinic antagonists on Ca2+ and K+ currents in frog and rat cardiac cells. AB - 1. The whole-cell patch clamp and intracellular perfusion techniques were used for studying the effects of atropine and other muscarinic acetylcholine receptor (mAChR) antagonists on the L-type calcium currents (ICa) in frog and rat ventricular myocytes, and on the mAChR-activated K+ current (IK(ACh)) in frog atrial myocytes. 2. In frog ventricular myocytes, atropine (0.1 nM to 1 microM) reversed the inhibitory effect of acetylcholine (ACh, 1 nM) on ICa previously stimulated by isoprenaline (Iso, 2 microM), a beta-adrenergic agonist. However, in the concomitant presence of Iso, ACh and atropine, ICa was > 50% larger than in Iso alone. 3. The effects of atropine were then examined in the absence of mAChR agonists. After a preliminary stimulation of ICa with Iso (0.1 or 2 microM), atropine induced a dose-dependent stimulation of ICa. EC50 (i.e. the concentration of atropine at which the response was 50% of the maximum) and Emax (i.e. maximal stimulation of ICa expressed as percentage increase in ICa with respect to the level in Iso alone) were respectively 0.6 nM and 35%. The stimulatory effect of atropine on ICa was not voltage dependent. 4. Atropine (1 microM) had no effect on frog ICa (i) under basal conditions, (ii) upon stimulation of ICa by the dihydropyridine agonist (-)-Bay K 8644 (1 microM), or (iii) when ICa had been previously stimulated by intracellular perfusion with cyclic AMP (3 microM). However, atropine increased ICa after a stimulation by forskolin (0.3 microM). Therefore, an increased adenylyl cyclase activity was required for atropine to produce its stimulatory effect on ICa. 5. The order of potency of mAChR antagonists to reverse the inhibitory effect of ACh on Iso elevated ICa in frog ventricle was atropine > AF-DX 116 >> pirenzepine. In the absence of ACh, mAChR antagonists produced their stimulatory effect on Iso elevated ICa with the same order of potency. 6. Intracellular substitution of Gpp(NH)p (5'-guanylylimidiphosphate) for GTP (420 microM) induced a strong inhibition of frog ICa in the presence of Iso (2 microM). This effect was attributed earlier to the spontaneous and irreversible activation of the GTP binding regulatory protein (G protein), Gi, responsible for adenylyl cyclase inhibition. Atropine (1 microM) slowed down by a factor of 2 the rate of ICa inhibition induced by Gpp(NH)p. 7. In frog atrial myocytes, intracellular perfusion with 1 mM Gpp(NH)p induces spontaneous activation of IK(ACh). This effect was attributed earlier to the spontaneous and irreversible activation of the G protein, GK.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350282 TI - Regional cerebral blood flow during volitional expiration in man: a comparison with volitional inspiration. AB - 1. Positron emission tomographic (PET) imaging of regional cerebral blood flow (rCBF), using a new 3-dimensional technique of data collection, was used to identify areas of neuronal activation associated with volitional inspiration and separately with volitional expiration in five normal male subjects. A comparison of the activated areas was also undertaken to isolate regions specific for one or other active task. 2. Scans were performed during intravenous infusion of H2(15)O under conditions of (a) volitional inspiration with passive expiration, (b) passive inspiration with volitional expiration and (c) passive inspiration with passive expiration. Four measurements in these three conditions were performed in each subject. Breathing pattern was well matched between conditions. 3. Regional increases in brain blood flow, due to increased neural activity associated with either active inspiration or active expiration, were derived using a pixel by pixel comparison of images obtained during the volitional and passive ventilation phases. Data were pooled from all runs in all subjects and were then processed to detect statistically significant (P < 0.05) increases in rCBF comparing active inspiration with passive inspiration and active expiration with passive expiration. 4. During active inspiration significant increases in rCBF were found bilaterally in the primary motor cortex dorsally just lateral to the vertex, in the supplementary motor area, in the right lateral pre-motor cortex and in the left ventrolateral thalamus. 5. In active expiration significant increases in rCBF were found in the right and left primary motor cortices dorsally just lateral to the vertex, the right and left primary motor cortices more ventrolaterally, the supplementary motor area, the right lateral pre-motor cortex, the ventrolateral thalamus bilaterally, and the cerebellum. 6. Using this modified and more sensitive PET technique, these findings essentially replicate those for volitional inspiration obtained in a previous study. For volitional expiration the areas activated are more extensive, but overlap with those involved in volitional inspiration. 7. The technique used has been successful in demonstrating the regions of the brain involved in the generation of volitional breathing, and probably in the volitional modulation of automatic breathing patterns such as would be required for the production of speech. PMID- 8350283 TI - Sound and vibration sensitivity of VIIIth nerve fibers in the frogs Leptodactylus albilabris and Rana pipiens pipiens. AB - 1. Responses of 73 fibers to dorso-ventral vibration were recorded in the saccular and utricular branchlets of Rana pipiens pipiens using a ventral approach. The saccular branchlet contained nearly exclusively vibration-sensitive fibers (33 out of 36) with best frequencies (BFs) between 10 and 70 Hz, whereas none of the 37 fibers encountered in the utricular branchlet responded to dorso ventral vibrations. 2. Using a dorsal approach we recorded from the VIIIth nerve near its entry in the brainstem and analyzed responses to both sound and vibration stimuli for 65 fibers in R. pipiens pipiens and 25 fibers in Leptodactylus albilabris. The fibers were classified as amphibian papilla (AP), basilar papilla (BP), saccular or vestibular fibers based on their location in the nerve. Only AP and saccular fibers responded to vibrations. The AP-fibers responded to vibrations from 0.01 cm/s2 and to sound from 40 dB SPL by increasing their spike rate. Best frequencies (BFs) ranged from 60 to 900 Hz, and only fibers with BFs below 500 Hz responded to vibrations. The fibers had identical BF's for sound and vibration. The saccular fibers had BFs ranging from 10 to 80 Hz with 22 fibers having BFs at 40-50 Hz. The fibers responded to sound from 70 dB SPL and to vibrations from 0.01 cm/s2. 3. No differences in sensitivity, tuning or phase-locking were found between the two species, except that most BP fibers in R. pipiens pipiens had BFs from 1.2 to 1.4 kHz, whereas those in L. albilabris had BFs from 2.0 to 2.2 kHz (matching the energy peak of L. albilabris' mating call). 4. The finding that the low-frequency amphibian papilla fibers are extremely sensitive to vibrations raises questions regarding their function in the behaving animal. They may be substrate vibration receptors, respond to sound-induced vibrations or bone-conducted sound. PMID- 8350284 TI - Visual performance of the toad (Bufo bufo) at low light levels: retinal ganglion cell responses and prey-catching accuracy. AB - The accuracy of toad snapping towards moving worm dummies under various levels of dim illumination (from absolute threshold to "moonlight") was video-recorded and related to spike responses of retinal ganglion cells exposed to equivalent stimuli. Some toads (at ca. 16 degrees C) successfully snapped at dummies that produced only one photoisomerization per 50 rods per second in the retina, in good agreement with thresholds of sensitive retinal ganglion cells. One factor underlying such high sensitivity is extensive temporal summation by the ganglion cells. This, however, is inevitably accompanied by very long response latencies (around 3 s near threshold), whereby the information reaching the brain shows the dummy in a position where it was several seconds earlier. Indeed, as the light was dimmed, snaps were displaced successively further to the rear of the dummy, finally missing it. The results in weak but clearly supra-threshold illumination indicate that snaps were aimed at the advancing head as seen by the brain, but landed further backwards in proportion to the retinal latency. Near absolute threshold, however, accuracy was "too good", suggesting that the animal had recourse to a neural representation of the regularly moving dummies to correct for the slowness of vision. PMID- 8350285 TI - Amine modulation of electrical coupling in the pyloric network of the lobster stomatogastric ganglion. AB - 1. The neurons of the pyloric network of the lobster (Panulirus interruptus) stomatogastric ganglion organize their rhythmic motor output using both chemical and electrical synapses. The 6 electrical synapses within this network help set the firing phases of the pyloric neurons during each rhythmic cycle. We examined the modulatory effects of the amines dopamine (DA), serotonin (5HT) and octopamine (Oct) on coupling at all the electrical synapses of the pyloric network. 2. Electrical coupling within the pacemaker group [anterior burster (AB) to pyloric dilator (PD), and PD-PD] was non-rectifying, while coupling at the other electrical synapses [AB to ventral dilator (VD), PD-VD, lateral pyloric (LP) to pyloric (PY), and PY-PY] was rectifying. 3. Dopamine decreased or increased the coupling strength of all the pyloric electrical synapses: the sign of the effect depended upon which neuron was the target of current injection. For example, DA decreased AB-->PD coupling (i.e., when current was injected into the AB) but increased coupling in the other direction, PD-->AB. Dopamine decreased AB to VD coupling when current was injected into either neuron. Serotonin also had mixed effects; it enhanced PD-->AB coupling but decreased AB to VD and PD to VD coupling in both directions. Octopamine's only effect was to reduce PD-->VD coupling. 4. Dopamine increased the input resistance of the AB neuron but decreased the input resistance of the PD and VD neurons. Serotonin reduced the input resistance of the VD and PY neurons, while Oct did not significantly change the input resistance of any pyloric neuron. 5. The characteristic modulation of electrical coupling by each amine may contribute to the unique motor pattern that DA, 5HT and Oct each elicit from the pyloric motor network. PMID- 8350286 TI - Reaction to surface waves by Xenopus laevis Daudin. Are sensory systems other than the lateral line involved? AB - The turning response to surface waves of clawed toads (Xenopus laevis) with an inactivated lateral line was reinvestigated to examine whether sensory systems other than the lateral line ("second systems") are involved. Two methods were used to block the lateral line input: selective and reversible inactivation of the lateral line periphery using CoCl2 or chronic destruction with thermocautery. The time-course of the response recovery (response frequency, turning accuracy and reaction time) was recorded. Following CoCl2 inactivation 10 out of 13 animals did not respond to surface waves for at least 2 days. The remaining 3 animals gave sporadic turning responses. It is assumed that in these individuals a "second system" is permanently involved in the detection of surface waves parallel to the lateral line. Five days after the chronic destruction of the lateral line all animals again turned to the centre of surface waves. It is suggested that by this time the "second system" had become capable of substituting for the missing lateral line input. The response frequency and the accuracy of the turning response of lesioned animals varied considerably among individuals but was always lower than in untreated animals (tested up to 120 days). PMID- 8350287 TI - Theoretical and empirical considerations on the relation between 'body image', body scheme and somatosensation. AB - The authors first discuss possible interactions between the hitherto neglected neurophysiological and neuropsychological factors and the traditionally accepted cognitive and affective factors in 'body image' formation. They then report on a study of the relation between body size perception (video distortion technique, image marking procedure, kinaesthetic size estimation apparatus) and somatosensation (thermal, pain and vibration thresholds) in young women. Included in the study were questionnaires on eating behaviour and motivation, body attitude or body satisfaction, and depressive mood and thoughts. Neither the somatosensory nor the questionnaire variables explained the difference between 'overestimators' and 'underestimators' of body size. However, these variables did explain the difference between 'good perceivers' and 'poor perceivers' (degree of deviation from actual body size) in the video distortion technique, with a somewhat larger contribution by the somatosensory variables. The latter finding, although clearly preliminary, should stimulate further investigations of the relationship between somatosensory variables and body size perception. PMID- 8350288 TI - Beta-endorphin response to exercise and mental stress in patients with ischemic heart disease. AB - We compared symptomatic, hemodynamic and opioid responses of heart disease patients to exercise testing and a stressful public speaking task. Plasma beta endorphins were measured at rest and immediately post stress. Nineteen of 50 patients had angina during exercise; 31 had asymptomatic ischemia. No patient had angina during the speech, but two had ECG changes and 39% had radionuclide changes indicating ischemia. Patients with asymptomatic ischemia on exercise had a significantly greater beta-endorphin response than those with angina. Public speaking elicited a significantly larger beta-endorphin increase relative to change in double product (an index of stress) than did exercise. CONCLUSIONS: (1) Patients with silent vs painful ischemia experience a greater beta-endorphin response to exercise. (2) beta-endorphin response to a speech stressor is greater than to exercise when controlled for an index of stress. (3) Increased beta endorphin response to a speech stressor may partially explain the predominance of silent ischemia during psychological stress. PMID- 8350289 TI - The physiological stress response and the role of cognitive coping in migraine patients and non-headache controls. AB - Our study investigated physiological response specificity and cognitive coping in migrainous patients during an achievement task situation. Thirty-three migrainous subjects and thirty-two non-headache controls were subjected to 40 min of demanding cognitive tasks and 20 min of recovery during which cranial and peripheral vasomotor responses were registered as well as electrodermal and myographic activity. Subjects of both groups were randomly assigned to two experimental conditions, a so-called 'spontaneous processing condition' and the 'positive coping treatment'. In this treatment condition subjects received a short training in the conscious use of positive self-statements in stress situations. Though a specific pattern of cranial vasomotor responses in migraine subjects could be verified by group statistics, this pattern was only found in very few individuals. Reliable differences between groups could not be identified in other physiological variables either. The hypothesis that the predicted cranial vasomotor specificity in migraine subjects correlates with negative cognitive coping habits in migraine subjects best revealed in the 'spontaneous processing' condition, was not corroborated. The treatment variation regarding coping produced somewhat paradoxical effects, more relaxed and positive self evaluation (subjective level) and more arousal (physiological level). Results are discussed for their impact on the psycho-biological model of migraine. PMID- 8350291 TI - Measurement reliability of cardiovascular reactivity change scores: a comparison of intermittent and continuous methods of assessment. AB - Cardiovascular reactivity testing is a widely used measure of risk for hypertension and coronary heart disease. Evidence for the reliability of the measures, however, is weak. If the measures (usually change scores) are unreliable, the usefulness of testing is limited, since relationships with other measures, such as disease outcomes, may be obscured. This study examines the reliability of blood pressure change, using both a traditional method of assessment (Colin ABPM) which provides intermittent readings, and a non-invasive method that samples the complete distribution of pressures (Ohmeda Finapres). While the reliability for the Colin was found to be good for absolute level of individual measurements, it was extremely poor for change scores. The Finapres, however, yielded high reliabilities for change scores as well as absolute levels, due to the large number of readings taken during baseline and stressor conditions. Implications for reactivity testing methodology are discussed. PMID- 8350290 TI - Mood state as a predictor of treatment outcome after in vitro fertilization/embryo transfer technology (IVF/ET). AB - The association between mood state and treatment outcome after In Vitro Fertilization/Embryo Transfer (IVF/ET) was assessed in a prospective sample of 330 women, of whom 113 were first time participants (inductees) and 217 were repeat cycle women (veterans). Initial evaluation of mood state indicated a significantly higher level of depression amongst veterans than inductees and a significantly greater proportion of veterans (25%) with clinically elevated depression scores compared with inductees (15%) and community norms (approx. 12%). Up to 12 months after initial assessment and after controlling for the number of treatment cycles, a significant difference was observed in the course of pregnancy over time between depressed and non-depressed women. Depressed women exhibited a lower pregnancy rate for the first treatment cycles than non depressed women. The results and their implications are discussed. PMID- 8350292 TI - Anger inhibition and family history as modulators of cardiovascular responses to mental stress in adolescent boys. AB - Sixty boys aged 12-16 took part in an experiment in which physiological and subjective measures were obtained at rest and in response to mental arithmetic and mirror drawing tasks. Blood pressure was recorded from biological parents, and subjects were subsequently categorized as being at high family risk for cardiovascular disease if either parent had a history of coronary heart disease or hypertension, or a resting blood pressure > or = 140/85 mmHg. Twenty boys were classified as high family risk and forty as low risk. A significant interaction between family risk and a disposition towards anger inhibition was observed, with the greatest systolic blood pressure responses to tasks being recorded in high risk boys who reported high levels of anger inhibition. This effect was maintained after controlling for initial blood pressure level, age and body mass. The cardiac baroreceptor reflex was inhibited during tasks, and was lower in high than low family risk subjects. The results suggest that the tendency to inhibit anger expression interacts with familial factors in determining reactivity patterns that may be indicative of raised risk of future cardiovascular disease. PMID- 8350293 TI - The Asthma Symptom Profile: a psychophysically based scale for assessment of asthma symptoms. AB - The Asthma Symptom Profile (ASP) assesses phasic changes in three dimensions of asthma symptoms: intensity, unpleasantness, and quality of sensations. Quantification data on verbal descriptors were gathered from 46 adult asthmatics for each of these scales, using bimodality scaling: i.e., with numerical estimates and drawing lines varying length. Close agreement was obtained between these two modalities. The ASP was analyzed before and after a bronchodilator in 44 asthmatics using ipratropium bromide (IB). Forty of these subjects were also tested in a placebo condition. Although ASP changes produced by IB were no greater than those produced by the placebo, correlations with changes in spirometry variables were significant. There were no significant differences in correlations with line drawings vs. numerical ratings. The ASP appears to be useful measure of phasic changes in asthma symptoms. Asthmatics with mild airway obstruction do not appear to be able to discriminate small changes in airway function. PMID- 8350294 TI - Coping with breast cancer over time and situation. AB - This study examines the variability and stability of coping in cancer subjects over time and situation. In a prospective longitudinal design 74 breastcancer patients have been followed for 3-5 yr at 3-6 monthly intervals. A variety of measures related to coping and adjustment were taken. This report limits itself to the findings of an instrument developed for this study, the Bernese Coping Modes in which 26 coping modes were rated by observers. Results confirm arguments in favour of both variability and stability in coping activity over time and situation. Two measures support stability: rank values and a multivariate measure (MDS) with three constant dimensions: (1) support and acceptance; (2) denial; (3) diversion by thought and action. Evidence for variability is: the potential range of coping modes and a large variety of additional modes at most observation times. Subsequently time measures of coping were attributed to eight predefined illness stages as distinct clinical situations. Thus variability or richness of coping further increased. The implications of these findings for measurement in coping research are discussed. PMID- 8350295 TI - Investigation of the reliability and factor structure of a questionnaire for assessment of the premenstrual syndrome. AB - Data are presented from 696 women who completed a 35-item retrospective self report PMS questionnaire. Item analysis resulted in the elimination of six items which predominantly reflected physical symptomatology. The resultant (29-item) questionnaire demonstrated a coefficient alpha value of 0.94 corresponding to a very high level of internal consistency and split-half reliability. It is argued that discrepancies in previous PMS research based on questionnaire data may, in part, be due to inadequate attention being devoted to achieving homogeneity of the PMS construct. A high level of internal consistency is a necessary condition for global PMS scores to be meaningful. Factor analysis of the revised questionnaire resulted in a two factor model corresponding to 'dysphoria' and 'dysfunction'. This leads to a simple four quadrant typology of PMS which may further understanding of this 'purer' PMS construct. PMID- 8350296 TI - 6-month aerobic exercise training program had no effect on cardiovascular responsivity to a mental arithmetic test in healthy middle-aged adults. PMID- 8350297 TI - Psychosocial factors in the progression of cervical intraepithelial neoplasia- CIN. PMID- 8350299 TI - Regulation of parental alloreactivity by reciprocal F1 hybrids. The role of lactation. AB - Adult reciprocal F1 hybrids differ in their susceptibility to parental graft versus host (GvH) reactions. These reactions were lower when the donor strain was syngeneic with the maternal one. Splenocytes from the member of the reciprocal pair in which the GvH reactions were lower also induced a decreased response of parental cells in cytotoxicity assays and in mixed lymphocyte reactions (MLR). The treatment with anti-CD8 plus complement was able to abrogate the different stimulatory ability of the reciprocal F1 spleen populations. Foster-nursing of F1 hybrids on mothers from the paternal strain was able to induce permanent alterations in the ability of their splenocytes to induce both parental anti-F1 MLR and CTL. The stimulatory ability was indistinguishable from that observed in the reciprocal F1 combination nursed on its own mother. Moreover, lactation was able to alter the ability of CD8+ spleen cells to regulate CTL and parental anti F1 MLR. The results reported herein show the existence of a maternal effect acting though milk capable of altering the regulation of parental alloreactive T reactions towards self histocompatibility antigens. PMID- 8350298 TI - An immunohistologic analysis of murine uterine T cells between birth and puberty. AB - Murine uterine T cells were analysed on the basis of surface phenotype expression from birth to adulthood. T cells were rare in the uterus from birth until 2 weeks of age. In genetically immunocompetent mice, mature T cells expressing either TCR alpha/beta or TCR gamma/delta were first present as a major cell population at 3 weeks of age. The ratio of TCR alpha/beta to TCR gamma/delta was 1:1 at 3 weeks of age and this ratio did not change during sexual maturation. Almost all uterine T cells were CD8+ and the majority of these cells expressed CD8 alpha/beta rather than CD8 alpha/alpha. Cells expressing Thy1.2 were less frequent than cells expressing CD3 while cells expressing CD5 were rare. No major changes in T cell subsets occurred at puberty. Further, the microbial flora of the mice did not alter the time of appearance, frequency or subset distribution of uterine TCR+ cells. In the uteri of immunodeficient mice of genotype scid/scid TCR+ cells were found in low numbers and the initial appearance of TCR+ cells was delayed until 5 weeks of age. PMID- 8350300 TI - Apical expression of an antigen common to rabbit yolk sac endoderm and kidney proximal tubule epithelium. AB - The tissue distribution, molecular weight, and biochemical nature of an antigen detected by a mouse monoclonal antibody designated 283D3 and raised against rabbit visceral yolk sac endodermal cells, has been investigated. The antigen is located on the luminal side of apical tubules and large sub-apical vesicles in rabbit yolk sac endoderm and proximal kidney tubule epithelial cells. It is expressed in a similar polarised fashion in epithelial cells lining the epididymis. Western blotting showed the antigen to comprise proteins of molecular weight 330-380 kDa. The antigen has been affinity purified from yolk sac and kidney and is predominantly protein in nature with a small percentage of N-linked carbohydrate. In terms of tissue distribution and molecular weight it has close similarity to Heymann nephritis antigen but differs in not being confined to coated pits. Its function is not known, but the association with endocytic elements implies a possible role in non-specific protein absorption. PMID- 8350301 TI - Impaired antibody diffusion within the cytoplasmic membrane-fibrous sheath interspace of the human sperm tail. AB - Monoclonal and polyclonal antibodies specific for the fibrous sheath (FS) were used to assess their diffusion within the subcytoplasmic membrane space of the human sperm tail. Using indirect immunofluorescence (IIF) and immunogold electron microscopy (IEM), the staining of the entire FS with these antibodies was observed only when the spermatozoa were completely demembranated by detergents or dried onto slides. Partial damage to sperm cytoplasmic membranes by freezing and thawing resulted in segmental staining of the FS. The IEM of such spermatozoa with the antibodies revealed the distribution of gold particles on the FS in denuded areas only and adjacent segments which retained their cytoplasmic membrane were not stained. These results indicate that partial disruption of the sperm plasma membranes does not lead to free diffusion of antibodies within the cytoplasmic membrane-FS interspace. This property appears to be unique to sperm cells and is due to their specialized structural organization. PMID- 8350302 TI - Paternity patterns and risk of preeclampsia in the last pregnancy in multiparae. AB - Few authors have published investigations regarding a possible association between preeclampsia and changing paternity. This study employs an epidemiological approach to explore the relationship between severe preeclampsia and changes in paternity patterns among multigravidae in a Caribbean community (Guadeloupe, French West Indies). Multiparae who were diagnosed with preeclampsia or eclampsia with fetal complications (transfer of their infants in the Neonatal Department) and controls were examined (134 mothers' interviews). Information concerning paternity for the index and previous pregnancies was collected from three groups: women with pregnancy-induced hypertension (PIH); women with chronic hypertension (CH); and a control group consisting of women without hypertension during pregnancy. In 21/34 (61.7%) of PIH mothers, the father of the current pregnancy was different than that of the former, compared to 4/40 (10%) among CH and 10/60 (16.6%) in the controls (P < 0.0001). Moreover, considering three and four consecutive pregnancies, there was a significant trend (P < 0.005 and P < 0.02) for an increase in PIH with having a different father in each successive pregnancy. Patterns of changing paternity were significantly correlated with pregnancy-induced hypertension in multiparae but not with chronic hypertension and controls. PMID- 8350303 TI - Secretory monoclonal IgA antibody to human sperm produced by gastrointestinal immunization inhibits human sperm activity and mouse in vitro fertilization. AB - BALB/c mice were immunized intragastrically with human sperm. Cells from the Peyer's patches and spleens of the immunized mice were for the preparation of hybridomas secreting antisperm monoclonal IgA (mcIgA). The specific ratio of IgA secreting cells in Peyer's patches was much higher than that in spleen. The binding site on human sperm of 9 of 19 mcIgA was in the post-acrosomal region using an immunofluorescent assay. Two of eight selected mcIgA caused strong human sperm agglutination and three of them produced significant inhibition of mouse in vitro fertilization. No mcIgA tested caused obvious human sperm immobilization or inhibited mouse in vivo fertilization. In vitro assembly of selected mcIgA in ascites with mouse secretory component (SC) caused no significant changes in effects on sperm function and in vitro fertilization. By use of Western blotting, dimer or higher polymers were demonstrated in all selected mcIgAs and corresponding protein antigens in 6 of 8 selected mcIgAs. These results suggest that human sperm function may be inhibited and fertilization rate reduced by specific secretory IgA to human sperm and that secretory immunity to protein antigens of human sperm could be induced by intragastrointestinal immunization. PMID- 8350304 TI - Effect of prostaglandin synthesis inhibitors on spontaneous and endotoxin-induced abortion in mice. AB - The putative role of prostaglandin E2 (PGE2) in suppressing rejection of the 'fetal allograft' (resorption) in C3H/HeJ and CBA/J allopregnant mice was tested by administration of the prostaglandin synthesis inhibitors indomethacin (INDO) and acetylsalicylic acid (ASA). When the resorption rate was low, INDO fed at a dose of 15 micrograms/ml in drinking water after implantation had a slight augmenting effect when the endogenous resorption rate was < 30%, but had no effect when the endogenous rate was higher or when bacterial lipopolysaccharide (LPS) was given. ASA fed at 50 micrograms/ml had no augmenting effect and did not increase sensitivity to the abortogen LPS in either CBA/J (LPS sensitive) or C3H/HeJ (LPS resistant) mice. Both INDO and ASA fed to CBA/J mice significantly reduced endogenous PGE2 extractable from the uteri of hormonally pseudopregnant mice after deciduoma induction. Feeding INDO at doses up to 30 micrograms/ml from day 2.5 of pregnancy impaired but failed to completely block implantation in CBA/J mice, and with daily administration, some of the mice became sick: all of the implants in sick mice resorbed. INDO at doses of 150-200 micrograms per day known to inhibit implantation in vivo by sufficiently blocking PGE2 synthesis, was injected on one or more days beginning after the time of implantation. This failed to cause abortion in CBA/J mice and although some mice became ill, provided this happened after day 8.5 of pregnancy when sensitivity to the abortogenic effects of injected LPS decreased substantially in these mice, all implants in the sick mice were 'healthy' (i.e. non-resorbing). We were unable to increase the rate of resorption in syngeneically pregnant CD1 mice above 13% with 15 ml INDO in drinking water. Our data do not support the view that PGE2 represents an important intrauterine suppressor molecular blocking the processes mediating embryo death at the time of abortion. Spontaneous abortion in DBA/2 mated CBA/J mice appears to be determined by the level of bacterial LPS (endotoxin) and treatment with antibiotics or intralipid (which enhances endotoxin clearance), reduces the abortion rate. A sufficient dose of INDO may cause abortion, but the data taken together suggest this may be due to effects on the gut whereby permeability to bacterial LPS is increased. PMID- 8350305 TI - Graves' autoimmune serum inhibits gonadal steroidogenesis: development of a Leydig cell bioassay to identify broad spectrum anti-endocrine autoantibodies. AB - In order to establish an assay for the detection of autoimmune sera with broad spectrum activity, we have investigated the effect of unselected normal and Graves' disease sera upon steroidogenesis by gonadal cells. Steroidogenesis was enhanced by the addition of normal serum in a 3-h primary Leydig cell bioassay, but was inhibited by the majority of Graves' sera. The inhibition was not related to clinical thyroid parameters, such as the severity of the TSH-binding inhibition index, and was not overcome by other agonists or second messenger supplements. Although pituitary TSH preparations bound to and stimulated Leydig cells, TSH receptor mRNA was not detectable and pure recombinant TSH failed to bind or stimulate, indicating contamination of pituitary TSH with LH. The binding of hCG to the Leydig cell luteinizing hormone receptor was not perturbed by the Graves' autoimmune sera, indicating that cross-reactive anti-TSH receptor antibodies were not responsible for the inhibition. By use of intermediates in the stimulatory pathway, the site of Graves' serum inhibition was identified to be distal to hormone receptor/adenylate cyclase coupled responses and proximal to supply of cholesterol for steroidogenesis. PMID- 8350306 TI - The relationship between spinal and peripheral osteoarthritis and bone density measurements. AB - OBJECTIVE: To determine the influence of osteoarthritis (OA) on bone density measurements and whether OA at one site is associated with OA at other sites. METHODS: Nonrandomized, cross sectional observational study; secondary analysis of a general population database. Sixty-four subjects derived from a longitudinal study of long distance runners and community controls had a complete peripheral radiographic evaluation for osteoarthritic changes in hands, knees, and lumbar spine. Forty-four of these were studied in 1984 with quantitative computed tomography (QCT) of L1, and 54 were studied in 1988 with 153-Gd dual photon absorptiometry (DPA) in the spine and total body. Thirty-four subjects had all measurements done. RESULTS: Total body and lumbar spine DPA were positively correlated with radiological scores of OA in the spine and knees, with coefficients ranging between 0.467 to 0.530 (p < 0.001 in all cases). This correlation was principally associated with spinal spurs and knee sclerosis. Results of stepwise multiple linear regression modeling for QCT included age, spine sclerosis, knee sclerosis and knee spurs as the main predictors of bone mineral density (BMD). For DPA measurements, spine spur score was a useful regressor for all the models. Altogether, the percentage of variance accounted for by individual radiological OA variables was 27.4% for lumbar QCT, 27.3% for lumbar BMD, 7.3% for total spine BMD, and 45.2% for total body BMD. OA scores at different sites were not correlated, although repeated assessment at the same site showed very close correlation. CONCLUSIONS: All methods used to determine BMD showed a highly significant positive correlation between lumbar and knee radiological OA and bone mineral content both in the spine and the total body. Thus, our results support the hypothesis that OA is negatively correlated with osteopenia. OA, as seen in this population, was not a generalized condition, but rather, was site specific. PMID- 8350307 TI - The inhibitory effect of tenidap on leukocyte-endothelial cell adhesion. AB - OBJECTIVE: Adhesion of neutrophils to vascular endothelial cells (EC) and neutrophil chemotaxis are essential processes which enable neutrophils to infiltrate the tissues. They represent potentially important targets for therapeutic intervention in inflammatory diseases. This study was conducted to test the effect of tenidap sodium on neutrophil adhesion and chemotaxis. METHODS: Adhesion of 51Cr sodium chromate labelled neutrophils to umbilical vein EC monolayers was assayed in 96-well microtiter plates. Neutrophil chemotaxis was measured in Boyden microchemotaxis chambers. RESULTS: Tenidap sodium caused a dose related inhibition of neutrophil adhesion to EC, with 50 microM tenidap resulting in 51.8 +/- 4.0% (mean +/- SEM) inhibition of unstimulated adhesion and 46.1 +/- 2.6% inhibition of formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated adhesion. A marked reduction in neutrophil chemotaxis in response to FMLP was also observed, with 50 microM and 100 microM tenidap leading to 83.4 +/- 8.5% and 92.1 +/- 8.5% (mean +/- SEM) inhibition respectively. The effect of tenidap on neutrophil adhesion to EC was not seen when neutrophils were preincubated with tenidap and then washed before adding to EC monolayers, suggesting an action upon surface molecules or in the cell membrane. Aspirin, indomethacin and phenylbutazone did not inhibit leukocyte adhesion, indicating that this action of tenidap may not be a consequence of inhibition of cyclooxygenase. The potency of tenidap was reduced by inclusion of serum or plasma in the culture medium, presumably due to protein binding. CONCLUSION: It is possible that inhibition of leukocyte-EC adhesion by tenidap sodium may contribute to the antiinflammatory effects of the drug. PMID- 8350308 TI - Influence of interferon-gamma on isolated chondrocytes from human articular cartilage. Dose dependent inhibition of cell proliferation and proteoglycan synthesis. AB - The effect of human recombinant interferon-gamma (IFN-gamma) on cultured human cartilage cells was studied by 2 variables: cell proliferation and proteoglycan synthesis. Cell proliferation was determined from 3H-thymidine incorporation rates in monolayer cultured chondrocytes. Proteoglycan synthesis was determined from 35S incorporation rates in monolayers and in chondrocytes cultured in agarose gel. IFN-gamma concentrations used in these experiments ranged from 10( 6) micrograms/ml (0.025 U/ml) to 10(-2) micrograms/ml (250 U/ml). The lowest concentrations are comparable with the synovial fluid levels in inflamed joints of patients with rheumatoid arthritis. At these concentrations, IFN-gamma was found to induce a dose dependent decrease of cell proliferation and of proteoglycan synthesis in monolayer cultured human chondrocytes. The decrease of proteoglycan synthesis was ascribed both to an inhibition of the proteoglycan protein core production and to a downregulation of the glycosaminoglycan chain elongation. PMID- 8350310 TI - The use of outcome measures to evaluate clinical rheumatology curriculum changes. AB - OBJECTIVE: Five years ago we sought to change the comprehensive educational program of our rheumatology clinical training period for internal medicine residents and develop a model to measure the outcome of the curriculum change. METHODS: During the month-long clinical training period in rheumatology, internal medicine residents participated in 10 interactive lectures on basic rheumatology with the faculty and worked through 26 case studies and radiographs of different rheumatic diseases with the faculty. Separate pre and posttests were developed and administered to the residents, both as evaluative and educational tools. Residents' performance on the rheumatology questions on the American Board of Internal Medicine (ABIM) examination were compared before and after the curriculum change. RESULTS: Comparison of pre to posttest results documented significant (p < 0.0001) improvement in the average resident score. Resident performance on the rheumatology questions of the ABIM examination improved markedly (average percentile rank for the 3 years before this change--55.7% versus the first 4 years after the change--82.5%; p < 0.05). CONCLUSION: This comprehensive educational program for internal medicine residents during the rheumatology clinical training period resulted in significant short and longterm increases in rheumatology knowledge base. PMID- 8350309 TI - A randomized trial of physicians and physical therapists as instructors of the musculoskeletal examination. AB - OBJECTIVE: To evaluate the effectiveness of physicians vs physical therapists as instructors of the musculoskeletal examination to second year medical students. METHODS: A randomized trial conducted over 3 consecutive years in a physical diagnosis course at The University of North Carolina. During the first (baseline) year, medical students received education about the musculoskeletal examination from a lecture and supervision by clinical preceptors. This increased in the second and third (intervention) years where random halves of each class received supplementary clinical instruction which included a structured manual, a videotape, and supervised practice with either general internal medicine physicians or physical therapists. Outcomes were measured from student performance on a practical test of clinical skills, and by written student evaluations of the supplementary instruction. RESULTS: As measured on the clinical examination, performance during the intervention years improved over that during the baseline year in both intervention groups. Measures of medical students' clinical skills did not correlate with measures of academic aptitude. CONCLUSIONS: Clinical education about the musculoskeletal examination should be structured and systematic. Medical students prefer clinical education that is active, provides clear directions, and gives them performance feedback. PMID- 8350311 TI - Modelling the population health impact of musculoskeletal diseases: arthritis. AB - OBJECTIVE: A model adjusting for reductions in quality and quantity of life was developed to estimate the population health impact of musculoskeletal diseases. METHODS: Using arthritis as the prototype, prevalence, mortality, and severity data from a variety of sources were combined to model a hypothetical cohort of 1,000 individuals through life. Quality adjusted life years and population health expectancy were calculated for those with arthritis and compared to the general population. RESULTS: Without adjusting for quality of life, a cohort of 1,000 women and 1,000 men at age 15 years could expect 65,010 and 58,735 life years, respectively. Adjusting for quality of life, women with arthritis could expect 61,719 life years, and men 57,123 life years. The unadjusted population health expectancy was 65.0 for girls and 58.7 for boys (at age 15 years). Adjusting for quality of life, the population health expectancies were 61.7 and 57.1, years for women and men, respectively. CONCLUSION: Using this model, the typical adult woman with arthritis can expect to lose 3.3 healthy years of life, and a man, 1.6 healthy years of life. Overall, the model provided a general methodology for determining the population health impact of musculoskeletal diseases. In addition, it is hoped that the methodology will stimulate further research into this area, raise awareness about the uses and limitations of currently available data, and provide a useful model for monitoring the impact of interventions. PMID- 8350312 TI - The development of systemic sclerosis (scleroderma) following augmentation mammoplasty. AB - We describe 3 patients developing systemic sclerosis (scleroderma) following breast augmentation with paraffin injections, and saline and silicone gel filled implants. Although previously considered inert, silicone appears capable of inducing human adjuvant disease including scleroderma in the susceptible individual. The occurrence of systemic sclerosis following the use of silicone implants however, appears to be uncommon. PMID- 8350313 TI - Primary pulmonary hypertension in a patient with systemic lupus erythematosus: partial improvement with cyclophosphamide. AB - Pulmonary hypertension was diagnosed in a patient with SLE after her 5th delivery. Time of onset and absence of thromboembolism and severe interstitial lung disease suggested primary pulmonary hypertension. Administration of vasodilators did not decrease pulmonary artery pressure which amounted to 82/30 mm Hg. Cyclophosphamide infusions, 0.5 g/m2 monthly for 6 months followed by once/3 months, in combination with 7.5 mg prednisolone daily resulted in decrease of pulmonary artery pressure to 66/34 mm Hg after 6 months of treatment persisting for 30 months. Intermittent infusions of cyclophosphamide with low dose prednisolone may be effective in primary pulmonary hypertension in SLE, suggesting an immune mediated pathogenesis. PMID- 8350314 TI - Reactive arthritis induced by Vibrio parahaemolyticus. AB - We describe a case of reactive arthritis after Vibrio parahaemolyticus infection. V. parahaemolyticus is the principal bacteria involved in the causation of foodborne gastroenterocolitis outbreaks in Japan. Several bacteria have been recognized as being involved in the development of reactive arthritis and this is the first report of reactive arthritis induced by V. parahaemolyticus. PMID- 8350315 TI - Vascular steal mimicking compression myelopathy in Paget's disease of bone: rapid reversal with calcitonin and systemic steroids. AB - Neurologic manifestations of Paget's disease of bone are primarily a result of mechanical compression on cranial nerves, spinal cord and roots. Less recognized is a myelopathy from "vascular steal" to highly vascularized and hypermetabolic pagetic bone. We describe a case of presumed ischemic myelitis in a patient with Paget's disease and aortic stenosis that was rapidly reversed with subcutaneous calcitonin and intravenous dexamethasone. PMID- 8350316 TI - Axillary lymphadenopathy due to Swanson implants. AB - We describe a case of unilateral axillary lymphadenopathy in an elderly woman with a long history of rheumatoid arthritis, 7 years status post placement of Swanson silastic elastomer implants in her right hand with good surgical outcome and with no outward reason for adenopathy. Though there was concern for malignancy, pathologic evaluation of the lymph node revealed foreign body giant cells reacting to silastic from her hand implants and no evidence of malignancy. This is only the 10th such case reported, despite the number of implants placed. PMID- 8350317 TI - Chronic diffuse sclerosing osteomyelitis of the humerus: novel treatment with calcitonin. AB - We describe a 51-year-old woman with a 20-year history of pain and swelling in her left upper arm. Radiographic appearance was suggestive of chronic osteomyelitis but confirmation necessitated surgical exploration. A diagnosis of sclerosing osteomyelitis was made on histology which responded poorly to the prolonged antibiotics. She subsequently made a dramatic symptomatic and radiological improvement after starting to take calcitonin, even in low dosage. PMID- 8350318 TI - Acute calcific periarthritis of the finger joints: a syndrome of women. AB - We describe a 33-year-old woman with acute calcific periarthritis (ACP) of the interphalangeal joint of the thumb and review 42 reported cases of ACP involving the finger joints. A computer assisted literature search for reported cases of ACP involving the finger joints was performed. Clinical features of our case and those fulfilling the criteria for entry into this study were analyzed. PMID- 8350319 TI - Photopheresis for scleroderma? Let's abandon the innuendos and get to the data. PMID- 8350320 TI - Microfocal radiography with macroradiographs in osteoarthritis. PMID- 8350321 TI - Hypersensitivity vasculitis and Henoch-Schonlein purpura: a comparison between the 2 disorders. PMID- 8350322 TI - Behcet's disease presenting as mediastinal mass. PMID- 8350323 TI - Specific increase of IgG antibody to 65 kDa heat shock protein but not to crude mycobacterial extract in RA. PMID- 8350324 TI - Augmentation mammoplasty: beauty or the beast? PMID- 8350325 TI - Folic acid supplementation during methotrexate therapy: it makes sense. PMID- 8350326 TI - Issues in rheumatology education: challenges for the nineties. PMID- 8350327 TI - Serial soluble interleukin 2 receptor levels in rheumatoid arthritis: differences in response to glucocorticoid treatment and chrysotherapy. AB - OBJECTIVE: To analyze the changes in soluble interleukin 2 receptor (sIL-2R) levels following treatment of patients with rheumatoid arthritis (RA). METHODS: Serial measurements of sIL-2R levels were made over 24 weeks in 40 patients with RA, treated with intramuscular (im) gold plus 3 im injections of either 120 mg methylprednisolone acetate or placebo. RESULTS: sIL-2R levels were reduced in the glucocorticoid treated group in contrast to the gold only group, where levels initially increased. At 24 weeks, mean sIL-2R levels did not significantly differ from pretreatment levels in either group, despite improvements in clinical measures. CONCLUSIONS: In our study, sIL-2R levels do not correlate with short term clinical measures of disease activity. Their significance for longer term prognostic use remains to be determined. PMID- 8350328 TI - Variability of immunologic and clinical features in patients with rheumatoid arthritis studied over 24 hours. AB - Disease activity measures in patients with rheumatoid arthritis (RA) are influenced by many factors. Bedrest has been long recognized to effect decreased disease activity. In addition, most patients note maximal levels of pain and stiffness in the early morning hours with improvement in the afternoon. Cytokines and hormones with circadian rhythms may also contribute to variability in disease status during the day. Our purpose was to investigate variability of clinical and immunologic measures over a 24-h period of hospitalization in patients with RA. Production of rheumatoid factors and immunoglobulins, joint counts and questionnaire evaluations were measured 3 to 6 times over a 24-h period of hospitalization in 10 patients with RA who were not receiving steroids or second line drugs. Total joint counts were significantly decreased as soon as 4 h after admission, and continued to decrease during the 24-h period of observation. Significant decreases in mononuclear cell proliferation and antibody synthesis were also observed. Our findings are consistent with the presence of decreased levels of immunostimulatory mediators in hospitalized patients especially during late afternoon or evening hours. PMID- 8350329 TI - Low dose leucovorin does not interfere with the efficacy of methotrexate in rheumatoid arthritis: an 8 week randomized placebo controlled trial. AB - OBJECTIVE: To determine if simultaneously administered low dose leucovorin interferes with the efficacy of methotrexate (MTX). METHODS: An 8-week double blind placebo controlled study of leucovorin (1 mg) in 16 patients with rheumatoid arthritis receiving chronic MTX was performed at a single academic center. RESULTS: A flare of disease activity was not observed. Clinical variables of arthritis activity did not change in the leucovorin treated population. CONCLUSIONS: Low dose leucovorin when taken simultaneously with MTX did not interfere with the efficacy of MTX in a short term 8 week trial. PMID- 8350330 TI - Immunosuppression by the disease modifying antirheumatic drug bucillamine: inhibition of human T lymphocyte function by bucillamine and its metabolites. AB - OBJECTIVE: Bucillamine: N-(2-mercapto-2-methyl-propanoyl)-L-cysteine has recently been suggested to be effective in the treatment of rheumatoid arthritis (RA). The molecular structure of this compound is similar to that of D-penicillamine, except that bucillamine has 2 free sulfhydryl groups in its structure whereas D penicillamine has only one. The goal of our studies was to determine whether bucillamine exerted immunosuppressive effects in vitro. METHODS: The effect of bucillamine and its metabolites on mitogen induced proliferation and IL-2 production by human T cells was examined. RESULTS: Bucillamine, and its metabolites SA 679, and SA 981 inhibited mitogen induced T cell responses. The inhibitory effect of bucillamine and SA 679, in which one sulfhydryl group is S methylated, was markedly augmented in the presence of CuSO4, and the effect was completely prevented by the addition of catalase. The capacity of SA 981, the internal disulfide of bucillamine, to inhibit T lymphocyte responses was not dependent on the presence of CuSO4. SA 672, in which both sulfhydryl groups are S methylated, did not inhibit T cell proliferation. CONCLUSION: Our results suggest that bucillamine has 2 distinct inhibitory effects on T cell function. One is the ability to generate H2O2 in the presence of CuSO4 and is attributable to its free thiol groups. The other is related to a separate inhibitory mechanism, that is not dependent on CuSO4 or the reduced thiol groups. These 2 immunosuppressive effects may account for the potency of bucillamine in suppressing rheumatoid inflammation. PMID- 8350332 TI - Bone marrow microenvironment of patients with systemic lupus erythematosus. AB - In an attempt to clarify the hematologic abnormality in systemic lupus erythematosus (SLE), we studied the bone marrow microenvironment of 8 women with this disease. The number of fibroblast colonies was similar to that of healthy control individuals. Culture supernatants of monocytes obtained from the patients with SLE showed a diminished production of the hemopoietic growth factor required to stimulate bone marrow fibroblasts. As the activity of the humoral factor released from SLE monocytes was diminished, such a reduction may play a role in the pathogenesis of the hematologic abnormality seen in SLE. PMID- 8350331 TI - Sjogren's syndrome in patients with interstitial cystitis. AB - OBJECTIVE: Patients with interstitial cystitis, a chronic nonbacterial inflammation of the bladder, were investigated for the presence of systemic autoimmune diseases, in particular for Sjogren's syndrome (SS). METHODS: Ten patients were included in the study on the basis of a diagnosis of interstitial cystitis according to usual criteria. They underwent clinical and laboratory investigations including those for keratoconjunctivitis (KCS) and focal lymphocytic sialoadenitis (FLS). RESULTS: In 2 patients both KCS and FLS were present allowing the diagnosis of primary SS according to classification criteria. Additionally, in 6 patients one of the 2 hallmarks of primary SS was present, KCS in 3 and FLS in 3. CONCLUSION: Interstitial cystitis is a new example of a disease that occurs in association with SS, supporting the concept that interstitial cystitis is an autoimmune cystitis. The clinical relevance of the finding is that a high index of suspicion for SS is indicated in patients with interstitial cystitis. PMID- 8350333 TI - An assessment of the Health Assessment Questionnaire functional ability index among women with systemic lupus erythematosus. AB - The validity of the Health Assessment Questionnaire (HAQ) functional ability instrument was tested in 120 women with definite systemic lupus erythematosus (SLE) from rheumatology clinics at 2 local tertiary care institutions. Reliability and validity results for this population of women (mean age: 41 years +/- 13; age at diagnosis 33 years +/- 13) indicate that (1) the HAQ was internally reliable (standardized alpha = 0.9443) with no interitem correlation exceeding (r = 0.75); (2) confirmatory factor analysis identified 2 predominant factors among the HAQ components suggestive of large limb gross movements (e.g., walking, arising) and small limb fine movements (e.g., the ability to eat and firmly grip objects). Cumulatively, the 2 factors accounted for 64% of the variation in HAQ ability response. The HAQ response was also valid when compared to the overall disability index (r = 0.65 to 0.82) and other common disease variables that were reported by the patient and collected by the physician at the time of clinical examination. In addition, when stratified by active and inactive disease as defined by the Lupus Activity Criteria Count, inactive patients reported lower disability components (dress, arise, eat, walk, hygiene, reach, grip and activity) than active patients. These findings confirm the valid use of the HAQ as a measure of disability, when compared with other clinical measures of disease status and activity, in female patients with SLE. PMID- 8350334 TI - Quality of life of women with systemic lupus erythematosus: a comparison with women with rheumatoid arthritis. AB - We assessed the quality of life and health status of 50 women with systemic lupus erythematosus (SLE) and compared them with 50 age matched women with rheumatoid arthritis (RA) using open ended questions, the Quality of Life Scale (QOLS-S), Arthritis Impact Measurement Scales (AIMS), Rheumatology Attitudes Index, and 2 measures of disease activity. The patients with SLE expressed more concerns about their disease and potential for managing it than the patients with RA. However, there were no differences between the groups on the QOLS-S. Both were highly satisfied with many aspects of their lives. The best predictor of life quality in both groups was psychological distress followed by social and physical functioning in the group with RA and perception of global impact of the disease in the group with SLE. PMID- 8350335 TI - Gamma delta + T cells from patients with psoriatic and rheumatoid arthritis respond to streptococcal antigen. AB - OBJECTIVE: To investigate cellular immune responses to streptococcal antigens in patients with psoriatic arthritis (PsA). To specifically examine responses of the gamma delta + T cell subset. METHODS: Proliferation of PsA synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) cultured with streptococcal antigen was measured using a 3H thymidine (3HTdr) uptake assay system. gamma delta + T cells from PsA PBL and SFL were phenotyped by flow cytometry. Following culture with streptococcal antigen, gamma delta + enriched SFL were sorted by automated flow cytometry and 3HTdr uptake measured. RESULTS: Patients with PsA and the control group did not differ significantly in their PBL responses to 2 strains of streptococci, one of which was isolated from a patient with guttate psoriasis (Strep 1) and the other from a patient with rheumatic fever (Strep 2). There was also no difference in their responses to a cell wall preparation derived from the former strain. SFL from 8 of 9 patients with PsA responded to both streptococcal strains as did SFL from 3 patients with rheumatoid arthritis (RA). gamma delta + SFL from 7 patients with PsA 3 patients with RA responded only to the psoriasis associated strain. CONCLUSIONS: PsA PBL and SFL responded to stimulation by streptococcal antigen but this reactivity was not disease specific. We have demonstrated that gamma delta + T cells from PsA SF proliferated when cultured with a psoriasis associated strain of streptococcus (Strep 1). However, RA gamma delta + SFL responded similarly suggesting that gamma delta + T cell reactivity to streptococcal antigen may be a feature of inflammatory arthritis. PMID- 8350336 TI - Higher relative risk of spondyloarthropathies among B27 positive Indonesian Chinese than native Indonesians. AB - We assessed the prevalence of HLA-B27 among ethnic Indonesian and Indonesian Chinese patients with ankylosing spondylitis (AS) or related spondyloarthropathies, and also among healthy controls. HLA-B27 was found in 23 (62.2%) of 37 Chinese patients and 4% of 176 Chinese healthy controls (p < 0.001). In contrasts only 2 (8.3%) of 24 native Indonesian patients and 13 (9%) of 145 healthy controls were HLA-B27+, indicating the lack of association of HLA B27 with spondyloarthropathies in native Indonesians. These findings also suggest that HLA-B27 Chinese Indonesians carry a greater relative risk of developing AS and related spondyloarthropathies than native Indonesians, although the prevalence of HLA-B27 in the general population is more than 2 times higher in native Indonesians. PMID- 8350337 TI - Fatigue in ankylosing spondylitis--why is it ignored? AB - OBJECTIVE: Fatigue in ankylosing spondylitis (AS) is largely ignored by physicians and classical texts. By contrast, patients frequently allude to it as a major complaint. METHODS: To address the situation, 3 studies were performed: (1) Symptoms were defined in a cross sectional evaluation of 1950 consecutive patients with AS. (2) From each of the 3 groups who specified a particular main symptom (pain, stiffness or fatigue), a random cohort of 20 was selected and all 60 were prospectively followed over a 14-day period. (3) An additional 100 patients [50 randomly selected with AS and 50 with rheumatoid arthritis (RA)] took part in a comparative prospective study. RESULTS: In the first study for those with a definitive major symptom, 34% (n = 670) described pain while stiffness and fatigue were reported by 25% (n = 492) and 6% (n = 124), respectively. Thirty-two percent (n = 616) could not distinguish between the 3. Strikingly, when prospectively studied over a 2-week period, over 50% of the patients revealed that fatigue was the main symptom. Moreover, in the cohort which expressed pain as their major problem initially, fatigue had the highest prevalence (mean fatigue value versus mean stiffness, p = 0.009; fatigue versus pain, p < 0.001). In the direct comparison between patients with RA and those with AS, the RA cohort had statistically more fatigue and pain than the AS cohort (p = 0.002, p = 0.007, respectively) with a similar amount of stiffness expressed by both groups (n = 0.149). In both subsets, pain had the least impact on the patients (mean 2.60 and 1.87, respectively). CONCLUSION: Our data reveal that fatigue should be considered a major problem for patients with AS, worthy of further exploration in terms of both etiology and therapy. PMID- 8350338 TI - Serial measurement of soluble interleukin 2 receptor levels: an early indicator of treatment response for Lyme disease. AB - Detection of antibodies produced in response to infection with Borrelia burgdorferi provides a valuable aid for diagnosing Lyme disease. However, anti Borrelial antibody titers are of little value in determining treatment success or providing evidence of persistent infection as levels of specific antibodies can remain elevated even after successful treatment. Pretreatment and posttreatment measurement of soluble interleukin 2 receptor (sIL-2R) levels was evaluated for use in predicting treatment response in Lyme disease. Results indicate that serial measurement of serum sIL-2R levels can provide an early indicator of response to treatment and outcome. PMID- 8350339 TI - A multicenter study of tenoxicam and diclofenac in patients with osteoarthritis of the knee. AB - OBJECTIVE: To conduct the first Canadian study of the comparative efficacy and safety of tenoxicam and diclofenac in patients with primary osteoarthritis (OA) of the knee. METHODS: Tenoxicam 20 mg per os once daily (po od) was compared to diclofenac (Voltaren) 50 mg per os 3 times a day (po tid) in a 12-week, double blind, randomized, controlled, multicenter, parallel trial. The primary outcome measure was the pain dimension of the WOMAC OA Index. Following an initial screening visit and a 3 to 7 day NSAID-free washout period (i.e., baseline), patients were assessed at Weeks 2, 4 and 12; assessments including some 15 efficacy variables and safety variables. RESULTS: Ninety-eight patients [tenoxicam (n = 48), diclofenac (n = 50)] participated in the trial. Statistically significant (p < or = 0.05) improvements in all 3 dimensions of the WOMAC OA Index and six efficacy variables were noted in both treatment groups. No significant between drug differences were noted on any efficacy variable. Significantly fewer patients reported adverse events in the tenoxicam group (21 vs 33, p = 0.03). CONCLUSION: Tenoxicam is efficacious and well tolerated in patients with OA of the knee. In this group of patients it was similar in efficacy and superior in tolerability to diclofenac 150 mg/day (50 mg tid). Thus the benefit/risk ratio of tenoxicam was superior to that of diclofenac in this study. PMID- 8350340 TI - Heritability of hostility-related emotions, attitudes, and behaviors. AB - Hostility-related variables have been categorized as to kinds of emotions, attitudes, and behaviors. Relatively few studies have explored whether genetic factors contribute to individual differences in these variables. Moreover, the majority of this research has involved male subjects. The present study utilized the twin method to evaluate the influence of genetic factors on hostility-related emotions, namely, trait anger and irritability, hostility-related attitudes, namely cynical hostility and suspiciousness, and hostility-related behaviors, namely, physical, verbal, and indirect aggression in adult women. Responses on the measure of trait anger showed evidence of significant heritability. However, evidence for a genetic component to responses on the irritability scale was less clear. There was no support for the notion of a genetic component to the measure of suspiciousness, and the evidence of a genetic contribution for cynical hostility was not significant. It was expected that due to environmental influences for women, only certain forms of aggression would show genetic variance, namely, verbal and indirect as opposed to physical forms. The results were generally congruent with these expectations. PMID- 8350341 TI - An analysis of relationships among environmental noise, annoyance and sensitivity to noise, and the consequences for health and sleep. AB - The complex relationship among long-term exposure to environmental noise, self reports of health, and sleep was investigated in a multifactorial design. Forty seven women and 35 men living beside a street with moderate to heavy traffic took part. They answered questions concerning health complaints, usual sleep patterns, sleep the actual week of testing, their subjective responses to noise, psychosocial relations, anxiety, stressful life events, type A behavior, and attitudinal factors that could explain their responses to noise. No detrimental relations among objective noise levels, health, and sleep could be shown. There were, however, strong correlations between the subjective noise responses of annoyance and sensitivity and health complaints. Only women revealed a relationship between poor sleep quality and sensitivity. The stronger relationship among noise sensitivity, health complaints, and poor sleep quality for women than for men could be explained by the degree of exposure to noise as evidenced by their longer residence and greater time spent at home. PMID- 8350342 TI - Cognitive function and cardiovascular responsivity in subjects with a parental history of hypertension. AB - College-age subjects with and without a parental history of hypertension completed a battery of tests of cognitive function on two separate occasions. Pulse rate and blood pressure were measured during performance of each task. In one session, subjects were told that their performance was being evaluated and videotaped from behind an observation mirror (Evaluation Condition). In the other session, subjects were told that their performance was not being observed (Nonevaluation Condition). Regardless of Evaluation Condition, Parental History subjects exhibited slower search of short-term memory than Non-Family History subjects during the first but not the second testing session. Parental History subjects displayed greater elevations in pulse rate than Nonparental History subjects during task performance. The results were interpreted as providing evidence that pathophysiological mechanisms associated with essential hypertension are not the only viable explanations of lower levels of cognitive performance exhibited by hypertensive subjects. PMID- 8350343 TI - Chemical analyses as validators in smoking cessation programs. AB - This review addresses the use of chemical analyses to validate the smoking status of a participant in a smoking cessation program. Pharmacokinetic and chemical validation literature leads to the conclusion that chemical analyses are most reliably used to confirm abstinence from smoking rather than as quantitative measures of nicotine intake or smoking activity. Analytical methodologies used in smoking validation studies are reviewed with their advantages and disadvantages. Close collaboration of behavioral scientists and analytical chemists is encouraged to validate the smoking status of participants in a smoking cessation program. PMID- 8350344 TI - Stress caused by rheumatoid arthritis: relation among subjective stressors of the disease, disease status, and well-being. AB - Two integrated studies, examining the chronic stressors specific to the disease rheumatoid arthritis, are described. Pain, limitation, and dependence were rated as the most annoying chronic stressors of the disease. Pain was measured with the Visual Analog Scale and the McGill Pain Questionnaire. Both pain scores were only weakly related to the medical assessment variables. New scales were developed to measure perceived limitation and dependence. Perceived limitation was inversely related to both mobility and self-care, but this association was not strong. Perceived dependence was unrelated to any of the health status measures. All three stressors were associated with indicators of quality of life even after controlling for interaction with clinical assessment and functional status variables. It was concluded from these studies that patients with rheumatoid arthritis must cope simultaneously with pain, limitation, and dependence. PMID- 8350345 TI - Factors related to the adoption of exercise among older women. AB - The role of exercise in promoting health is well documented; however, older women have the lowest rates of aerobic exercise of any community group. This paper examines psychological variables relevant to women's initial adoption of exercise. While the evidence is limited, it appears that middle-aged and older women have positive attitudes to exercise but seem unable or unwilling to take action. The influence of practical barriers and of broader social attitudes is considered. It is concluded that social psychological variables have had limited success in explaining sex differences in physical activity. An understanding of practical and societal constraints on behavior choice in a broader social context may provide direction for the development of strategies to improve the exercise levels of this community group. PMID- 8350346 TI - The evolution of the thrombospondin gene family. AB - Thrombospondin-1 is an adhesive glycoprotein that is involved in cellular attachment, spreading, migration, and proliferation. To date, four genes have been identified that encode for the members of the thrombospondin gene family. These four genes are homologous to each other in the EGF-like (type 2) repeats, the calcium-binding (type 3) motifs, and the COOH-terminal. The latter has been reported to be a cell-binding domain in thrombospondin-1. Phylogenetic trees have been constructed from the multisequence alignment of thrombospondin sequences from human, mouse, chicken, and frog. Two different algorithms generate comparable results in terms of the topology and the branch lengths. The analysis indicates that an early form of the thrombospondin gene duplicated about 925 million years ago. The gene duplication that produced the thrombospondin-1 and -2 branches of the family is predicted to have occurred 583 million years ago, whereas the gene duplication that produced the thrombospondin-3 and -4 branches of the family is predicted to have occurred 644 million years ago. These results indicate that the members of the thrombospondin gene family have existed throughout the evolution of the animal kingdom and thus probably participate in functions that are common to most of its members. PMID- 8350347 TI - Distribution of polymorphic gene duplication at the Gpdh locus in natural populations of Drosophila melanogaster. AB - The glycerol-3-phosphate dehydrogenase (GPDH, E.C. 1.1.1.8) gene of Drosophila melanogaster contains a tandem duplication of a 4.5-kb-long DNA fragment. Survey of the Gpdh gene region by the Southern blot analysis revealed the following features of this gene duplication: (1) The duplication was not observed in chromosome lines that carry In(2L)t, a cosmopolitan chromosomal inversion in this species. The duplication and the inversion are in linkage disequilibrium. (2) The duplication is polymorphic in the Japan and US natural populations examined. Its frequency is 0.26 on an average in In(2L)t-free chromosomes. (3) Triplication is absent or has not become frequent in the populations surveyed. Possible evolutionary factors of this duplication polymorphism are discussed. PMID- 8350348 TI - Evolution of the dec-1 eggshell locus in Drosophila. II. Intraspecific DNA sequence analysis reveals length mutations in a repetitive region in D. melanogaster. AB - The dec-1 eggshell gene in Drosophila melanogaster encodes follicle cell proteins required for proper eggshell assembly. As shown by Southern and Northern analyses the dec-1 gene occurs in four alleles (Fc1-4) among wild-type strains. Its second exon has a distinct feature in the form of 12 repeats with 78-91 nucleotides; the first five show nearly 100% homology. DNA sequence comparison of the repeated region of the alleles revealed that the length polymorphisms are caused by changes in the numbers of the first five repeats. The results suggest that the alleles have been generated by unequal intragenic crossing-over and/or slippage during DNA replication and that the allelic length variants have arisen independently. The possibility that the most common allele, FC1, has a selective advantage over the other alleles is discussed. PMID- 8350349 TI - The phylogeny of echinoderm classes based on mitochondrial gene arrangements. AB - Previous analyses have demonstrated that, among the echinoderms, the sea star (class: Asteroidea) mitochondrial genome contains a large inversion in comparison to the mitochondrial DNA of sea urchins (class: Echinoidea). Polymerase chain reaction amplification, DNA cloning, and sequencing have been used to examine the relationships of the brittle stars (class: Ophiuroidea) and sea cucumbers (class: Holothuroidea) to the sea stars and sea urchins. The DNA sequence of the regions spanning potential inversion junctions in both brittle stars and sea cucumbers has been determined. This study has also revealed a highly modified tRNA cluster in the ophiuroid mitochondrial genome. Our data indicate mitochondrial gene arrangement patterns that group the sea cucumbers with sea urchins and sea stars with brittle stars. This use of molecular characters clarifies the relationships among these classes. PMID- 8350350 TI - Domains within the mammalian ornithine decarboxylase messenger RNA have evolved independently and episodically. AB - Ornithine decarboxylase (ODC) is the first enzyme in the polyamine biosynthetic pathway. We have studied the evolutionary history of the mammalian ODC mRNA, focusing on the rate of accumulation of sequence divergence within specific subregions of the molecule. The phylogenetic relationships among the mRNAs from several mammalian species, including two mouse species, rat, hamster, and human, were determined based upon the numbers of synonymous substitutions in pairwise comparisons of mRNA coding regions. The separation times for the mRNAs were very similar to those for the corresponding species, suggesting that ODC is encoded by orthologous genes in the different species. Analysis of divergence patterns in four subregions, or domains, of the mRNA (the 5'-untranslated region, the coding region, and two domains of the 3'-untranslated region) showed that the domains have evolved in a noncoordinate fashion. Furthermore, evolution of each subregion has been episodic, with periods of both rapid and slow sequence divergence. We suggest that the episodic pattern of ODC mRNA evolution may indicate the existence of selection pressures that were exerted in a time- and domain-specific manner during mammalian speciation. PMID- 8350351 TI - Molecular analysis of ependymins from the cerebrospinal fluid of the orders Clupeiformes and Salmoniformes: no indication for the existence of an euteleost infradivision. AB - Ependymins represent the predominant protein constituents in the cerebrospinal fluid of many teleost fish and they are synthesized in meningeal fibroblasts. Here, we present the ependymin sequences from the herring (Clupea harengus) and the pike (Esox lucius). A comparison of ependymin homologous sequences from three different orders of teleost fish (Salmoniformes, Cypriniformes, and Clupeiformes) revealed the highest similarity between Clupeiformes and Cypriniformes. This result is unexpected because it does not reflect current systematics, in which Clupeiformes belong to a separate infradivision (Clupeomorpha) than Salmoniformes and Cypriniformes (Euteleostei). Furthermore, in Salmoniformes the evolutionary rate of ependymins seems to be accelerated mainly on the protein level. However, considering these inconstant rates, neither neighbor-joining trees nor DNA parsimony methods gave any indication that a separate euteleost infradivision exists. PMID- 8350353 TI - Sequence homology between a bacterial metalloproteinase and eukaryotic matrix metalloproteinases. AB - The origin and evolution of matrix metalloproteinases represent an exciting subject of study. Recently, various reports have searched for a relationship between bacterial and eukaryotic metalloproteinases. In this report, we constructed a phylogenetic tree using the amino acid sequence of one bacterial metalloproteinase and eight eukaryotic matrix metalloproteinases and performed multiple alignments with some of these sequences. We concluded that there is a familial relationship between members of the four major branches represented in the tree. PMID- 8350352 TI - Development of artificial neural filters for pattern recognition in protein sequences. AB - Four different artificial neural network architectures have been tested for their suitability to extract and predict sequence features. For optimization of the network weights an evolutionary computing method has been applied. The networks have feedforward architecture and provide adaptive neural filter systems for pattern recognition in primary structures and sequence classification. The recognition and prediction of signal peptidase cleavage sites of E. coli periplasmic protein precursors serves as an example for filter development. The primary structures are represented by seven physicochemical residue properties. This amino acid description provides the feature space for network optimization. The properties hydrophobicity, hydrophilicity, side-chain volume, and polarity allowed an accurate classification of the data. A three-layer network architecture reached a learning success of 100%; the highest prediction accuracy in an independent test set of sequences was 97%. This network architecture appears to be most suited for the analysis of E. coli signal peptidase cleavage sites. Further suggestions about the design and future applications of artificial neural networks for protein sequence analysis are made. PMID- 8350354 TI - A differential molecular clock in enolase isoprotein evolution. PMID- 8350355 TI - Tamoxifen: how boldly to go where no women have gone before. PMID- 8350356 TI - Breast cancer and silicone implants: psychological consequences for women. PMID- 8350357 TI - Media coverage of cancer risks may mislead. PMID- 8350359 TI - European Cancer Center links basic and clinical science. PMID- 8350358 TI - AIDS-related cancers emerging as a second epidemic. PMID- 8350360 TI - Dutch cancer care is (was?) well supported. PMID- 8350361 TI - Scientists gain insight into cancer gene relationships. PMID- 8350362 TI - AIDS-related malignancies: the emerging epidemic. AB - The incidence of three malignancies has increased in conjunction with the epidemic of human immunodeficiency virus (HIV) disease, and they are currently considered acquired immunodeficiency syndrome (AIDS)-defining conditions. These are Kaposi's sarcoma, associated with AIDS since the onset of the epidemic in 1981; intermediate or high-grade B-cell lymphoma, which became AIDS-defining in 1985; and cervical carcinoma in HIV-infected women, formally recognized as an AIDS-defining diagnosis on January 1, 1993. Approximately 40% of all patients with AIDS have developed cancer during the course of HIV infection. Further, as survival has improved in HIV disease, the incidence of these malignancies has increased. It is thus expected that greater numbers of patients with AIDS-related lymphoma and cervical cancer will be diagnosed in the years ahead. The epidemiologic factors associated with neoplastic disease differ among patients with the three AIDS-related malignancies. The pathogenesis of neoplastic disease also differs. The specific etiologic steps in the development of AIDS-related Kaposi's sarcoma and lymphoma are currently unknown. However, a great deal of information has already been acquired, which may have bearing on the pathogenesis of malignant disease in general, as well as the elucidation of future therapeutic modalities. The specific epidemiologic, etiologic, and clinical characteristics of the AIDS-related malignancies will be described herein. It is hoped that this review will serve to outline our current understanding of this area, to introduce the questions and controversies which are apparent in the field, and to mention those areas in which future research might be focused. PMID- 8350363 TI - Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. The Stockholm Breast Cancer Study Group. AB - BACKGROUND: Tamoxifen, which binds to estrogen receptors, is widely used as adjuvant therapy after surgery for early-stage breast cancer. Our previous randomized trial of adjuvant tamoxifen therapy for breast cancer showed a significant decrease of new, contralateral breast cancers in patients who received tamoxifen. Tamoxifen may also influence risk factors for cardiac and thromboembolic disease (e.g., serum cholesterol and antithrombin III). PURPOSE: The purpose of this study was to assess morbidity from cardiac and thromboembolic disease among 2365 postmenopausal patients with early-stage breast cancer in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus no adjuvant endocrine therapy. Patients were entered in the study from November 1976 through December 1988. METHODS: In our retrospective study, the analysis of morbidity was based on data from a computerized, population-based register of hospital admissions and discharge diagnoses. Mortality data were obtained from the Swedish National Central Bureau of Statistics. In the Stockholm study, treatment with tamoxifen was initiated within 4-6 weeks of modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection and postoperative radiation therapy to the breast. In that randomized trial, 755 patients at low risk of death from breast cancer received adjuvant tamoxifen only; 760 received no treatment. In addition, 628 high-risk patients were randomly assigned to receive adjuvant chemotherapy plus tamoxifen (173 patients) or postoperative radiotherapy plus tamoxifen (151) or, as a control, to receive chemotherapy (171) or postoperative radiation therapy (133), both without tamoxifen or other endocrine therapy. Median follow-up was 6 years. RESULTS: Tamoxifen therapy resulted in a statistically significant reduced incidence of hospital admissions due to cardiac disease. The relative hazard (tamoxifen for 2 or 5 years versus control) was 0.68 (95% confidence interval [CI] = 0.48-0.97; P = .03). In the randomized comparison of 5 versus 2 years of tamoxifen, there was a statistically significant difference favoring the longer treatment (relative hazard = 0.37; 95% CI = 0.15-0.92; P = .03). There was little difference between the tamoxifen and control groups in terms of admissions due to thromboembolic disease. CONCLUSIONS: These findings suggest that long-term adjuvant treatment with tamoxifen may result in substantial reduction of cardiac morbidity in patients with low risk of death from breast cancer as well as in women in chemopreventive studies who have high risk of developing breast cancer. IMPLICATIONS: Our results support continuation of ongoing trials of tamoxifen therapy in these two groups of subjects. PMID- 8350364 TI - Silicone controversy: a survey of women with breast cancer and silicone implants. AB - BACKGROUND: During the past 3 years, there has been a highly publicized debate concerning the potential medical complications of silicone breast implants. There have been no studies that have addressed the effect of this controversy on women with a history of breast cancer who have undergone breast reconstruction with silicone implants. PURPOSE: This study was undertaken to understand the concerns of such women regarding their breast reconstructions and to assess what impact the silicone implant controversy had on them. METHODS: One hundred seventy-four randomly selected women who had undergone reconstructive surgery with silicone implants subsequent to mastectomy for treatment of breast cancer were interviewed by telephone from February through May 1992. (A moratorium on use of silicone breast implants, imposed by the Food and Drug Administration, extended from January through April 1992.) These women, a subset of 359 mastectomy/reconstruction patients of one university-based plastic surgeon, had their first permanent prostheses placed between 1985 and 1990. The interview included questions designed to elicit information about women's experiences with reconstruction and reactions to the controversy. RESULTS: All study participants were aware of the controversy surrounding silicone implants. Seventy-six percent stated that breast reconstruction helped them cope with cancer, and only 16% had regrets about reconstruction. Many respondents had misconceptions about the nature of possible complications from silicone implants. Fifty-five percent were worried about the implants, yet only 13% considered having them removed as a result of the controversy. Only 27% indicated they would be completely likely to choose silicone implants again. The majority of women were unwilling to accept substantial risks of complications from implants, but there was variability in the level of risk that respondents would tolerate. CONCLUSIONS: A majority of women who have had breast reconstruction using silicone implants after treatment of breast cancer believe that implants helped them cope with the cancer. However, a sizeable proportion of such women are worried about possible medical complications that may develop as a consequence of silicone breast implants. Many would likely not choose these implants today. IMPLICATIONS: The true risks associated with silicone implants will ultimately be known. In the meantime, health care providers need to address patients' concerns about these implants. Information and guidance regarding the potential benefits and risks of breast implant devices should be provided to women with breast cancer who are considering treatment options. PMID- 8350365 TI - Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro. AB - BACKGROUND: Antiestrogens inhibit the stimulative effects of estrogens on breast cancer growth, but the mechanism(s) by which they trigger tumor regression are not completely understood. Growth retardation and tumor regression can be achieved by enhanced cell death and/or arrested cell proliferation. PURPOSE: Our aim was to investigate the effect of a new antiestrogen, toremifene, on human breast cancer cells grown either in culture or as tumors in nude mice. METHODS: The growth and morphology of in vitro cultured cells of the human breast cancer cell line MCF-7 were monitored by time-lapse video. MCF-7 cells and ZR-75-1 human breast cancer cells were grown as tumors in nude mice and subsequently examined by electron microscopy. The integrity of DNA isolated from these cells was determined by standard gel electrophoretic techniques. Northern blot hybridization analysis was used to determine the steady-state levels of the mRNAs for testosterone-repressed prostatic message-2 (TRPM-2), tumor growth factor beta 1 (TGF beta 1), and pS2 (a small, cysteine-rich protein of unknown function). RESULTS: Time-lapse video microscopy of the cell cultures indicated that treatment with 7.5 microM toremifene for 3 days caused approximately 60% of the cells to exhibit morphologic characteristics typical of cells undergoing programmed death, or apoptosis. The number of mitoses gradually decreased to zero over a 3- to 4-day period. Estrogen withdrawal for the same length of time resulted in an approximately equal number of apoptoses and mitoses. These changes were not associated with the pattern of DNA fragmentation, detectable as ladders in agarose gels, that is characteristic of the DNA of cells undergoing apoptosis. Elevated levels of TRPM-2 and TGF beta 1 mRNAs were observed in in vitro or in vivo grown tumor cells treated with 5-10 microM toremifene. Elevated levels of TRPM-2, but not TGF beta 1, mRNA were observed in the tumor cells after estrogen withdrawal. The steady-state level of pS2 mRNA in the tumor cells dropped in response to either toremifene treatment or estrogen withdrawal. CONCLUSION: Toremifene causes growth inhibition of estrogen-sensitive breast cancer cells by inducing some cells to undergo apoptosis and by inhibiting other cells from entering mitosis. The higher than normal amounts of TRPM-2 and TGF beta 1 protein that would likely result from the elevated levels of TRPM-2 and TGF beta 1 mRNAs measured in these cells after toremifene treatment may have an important role in the growth inhibition process. IMPLICATION: Apoptosis as an active, targeted process provides a potential new therapeutic approach for treating breast cancer. PMID- 8350366 TI - Unregulated and independent expression of collagenase and transin related to tumor progression. PMID- 8350367 TI - Videos as an educational intervention for childhood asthma among urban blacks. PMID- 8350369 TI - Depression in primary care: guideline overview. Agency for Health Care Policy and Research. PMID- 8350368 TI - Cold preservation of enteric free flaps. PMID- 8350370 TI - Managed care now and forever. PMID- 8350371 TI - The NIH agenda for women's health. PMID- 8350372 TI - Low birthweight in African Americans: does intergenerational well-being improve outcome? AB - The primary antecedent of infant mortality is low birthweight. Vital statistics data have shown that women of low socioeconomic status, regardless of race, are at greater risk for delivering low birthweight infants; however, prevailing data show that black women of the same socioeconomic status as white women have a twofold higher risk of giving birth to an infant weighing < 2500 g and a threefold risk of delivering a very low birthweight infant weighing < 1500 g. There is also evidence that intergenerational effects on birth outcome exist. However, virtually all studies of the effect of socioeconomic status on perinatal outcome have been cross-sectional; the effect of sustained intergenerational well being has not been measured. To address this gap, this study was designed to demonstrate that in an African-American population with sustained high socioeconomic status and equal risk factors, the birthweight distribution and other reproductive outcomes are the same as those for comparable US white populations. Preliminary findings are reported here. PMID- 8350373 TI - The health status of African-American elderly. AB - This article reviews the health status of African-American elderly, based on a computerized search of the medical literature from 1987 to 1991, as well as careful review of the report of the Secretary of Health's Task Force on Black and Minority Health. Black Americans have a higher prevalence of malignancies, diabetes, hypertension, obesity, homicide, and unintentional injury than white Americans. These problems contribute to a high mortality rate in young blacks and a greater prevalence of problems with activities of daily living in elderly blacks. Despite the high disease burden among young blacks, blacks are living progressively longer. As the number of elderly blacks increases, health-care practitioners will need to increase risk factor reduction in young-old blacks. Additionally, there will be a need for increased support of physical functioning in elderly African American. PMID- 8350374 TI - Retention of traditional premedical students in a medical career pathway compared with students in a combined baccalaureate-medical degree program. AB - This study compared the retention in medical career pathways of students enrolled in a combined baccalaureate-medical degree program to traditional premedical students at Brown University. Whereas 84% of the combined-degree students went on to medical school, only 36% of the traditional premedical students did. Among underrepresented minority students, the proportions were 74% and 39%, respectively. Scholastic Aptitude Test (SAT) scores accounted for some of the difference, yet even when SAT scores were controlled using a multiple logistic regression model, students enrolled in the combined-degree program were more than eight times as likely to continue in a medical career pathway. PMID- 8350375 TI - Risk and outcome of aspiration pneumonia in a city hospital. AB - Because aspiration pneumonia contributes significantly to morbidity and mortality in hospitalized patients, this study was undertaken to identify risk factors for morbidity and mortality associated with aspiration pneumonia. Patients with a discharge diagnosis of aspiration pneumonia in 1985 and 1990 were studied. Factors associated with death from aspiration pneumonia were: altered mental status, cerebrovascular accident, endotracheal intubation, tachycardia, and hypoxemia. Fever, cough, and unilateral infiltrates on chest radiograph were associated with survival. Attention to proper positioning of comatose patients, aggressive treatment of gastroesophageal reflux, and strict attention to endotracheal tubes and tracheostomies should decrease the morbidity and mortality associated with aspiration pneumonia. PMID- 8350376 TI - Diabetes-related complications of pregnancy. AB - Diabetes mellitus is a major medical complication of pregnancy and is associated with an increased risk of maternal and perinatal morbidity and mortality. Although recent advances have improved outcomes dramatically, the increased incidence of congenital malformations remains a significant problem. In the past, it was believed that pregnancy worsened microvascular complications, and women with vasculopathy were counseled to avoid or terminate pregnancies. Recent evidence suggests that normalization of blood glucose levels and current management strategies can lead to improved outcomes even in women with vasculopathy. Today, with the exception of coronary artery disease, women with diabetes may be counseled toward a more favorable outcome. This article discusses preconception planning and contemporary treatment methods. PMID- 8350377 TI - The clinical and radiological evaluation of primary brain neoplasms in children, Part II: Radiological evaluation. AB - Data collected over the past 8 years on the radiological appearance of common pediatric primary brain neoplasms are presented. An emphasis is placed on the newer radiological imaging modality of magnetic resonance imaging (MRI). Part I of this article emphasized the clinical evaluation of these brain neoplasms. Three hundred eighty-five children with known brain neoplasms ranging in age from newborn to 18 years were evaluated with one or all of the following radiological modalities: MRI, computed tomography (CT), water-soluble myelography (WSM), WSM with CT, and angiography. Contrast-enhanced MRI and CT scans both were accurate in delineating these brain neoplasms although MRI provided better resolution and delineation than CT. Angiography provided information on the vascularity of the neoplasms and their relationship to prominent arterial and venous structures. Water-soluble myelography with CT and gadolinium-enhanced MRI of the spine were equally accurate in demonstrating metastatic spread to the spinal canal and spinal cord. Magnetic resonance imaging with gadolinium was more accurate than CT with contrast in demonstrating recurrent or residual neoplasm at the operative site and metastatic spread to the brain. Magnetic resonance imaging with gadolinium is the best radiological modality to fully evaluate pediatric brain neoplasms. PMID- 8350378 TI - Assessed diversity within a regional organization of student representatives group. AB - This pilot study assessed diversity within an Organization of Student Representatives (OSR) group attending the 1990 Annual Meeting of the Southern Region Group on Student Affairs. In contrast to the Southern Region medical student population, the OSR group had a higher rate of students who were older, female, non-science majors in college, and in preclinical years of medical school. While the findings suggest that barriers are being overcome, underrepresented minority students also were underrepresented in the OSR group. A larger study should be conducted to determine OSR minority representation nationwide. PMID- 8350379 TI - Purtscher's retinopathy: a case of visual impairment associated with multiple trauma. AB - This case study describes a patient with multiple trauma associated with acute visual impairment. Funduscopic examination revealed scattered and confluent cotton wool exudates bilaterally. This retinopathy was first described by Othmar Purtscher, an Austrian ophthalmologist, in 1910, which he later referred to as "angiopathia retinae traumatica." PMID- 8350380 TI - Idiopathic peripheral gangrene in Nigeria. AB - A severe, acutely evolving peripheral gangrene of unknown etiology has been reported sporadically from different parts of Africa. This case report describes such a case of fulminant gangrene of the extremities following a febrile diarrheal illness associated with abdominal pain, polyarthropathy, and altered hemostatic function in a black adolescent male. A model of autoimmune causation for this uncommon clinical syndrome is proposed with guidelines for therapy. PMID- 8350381 TI - Genotoxicity studies in semiconductor industry. 1. In vitro mutagenicity and genotoxicity studies of waste samples resulting from plasma etching. AB - Solid waste samples taken from the etching reactor, the turbo pump, and the waste air system of a plasma etching technology line in semiconductor production were studied as to their genotoxic properties in a bacterial repair test, in the Ames/Salmonella microsome assay, in the SOS chromotest, in primary mouse hepatocytes, and in Chinese hamster V79 cell cultures. All three waste samples were found to be active by inducing of unscheduled DNA-synthesis in mouse hepatocytes in vitro. In the bacterial rec-type repair test with Proteus mirabilis, waste samples taken from the turbo pump and the vacuum pipe system were not genotoxic. The waste sample taken from the chlorine-mediated plasma reactor was clearly positive in the bacterial repair assay and in the SOS chromotest wit Escherichia coli. Mutagenic activity was demonstrated for all samples in the presence and absence of S9 mix made from mouse liver homogenate. Again, highest mutagenic activity was recorded for the waste sample taken from the plasma reactor, while samples collected from the turbo pump and from the waste air system before dilution and liberation of the air were less mutagenic. For all samples chromosomal damage in V79 cells was not detected, indicating absence of clastogenic activity in vitro. Altogether, these results indicate generation of genotoxic and mutagenic products as a consequence of chlorine mediated plasma etching in the microelectronics industry and the presence of genotoxins even in places distant from the plasma reactor. Occupational exposure can be expected both from the precipitated wastes and from chemicals reaching the environment with the air stream. PMID- 8350382 TI - Immunoelectrophoretic pattern of native mucosal intracellular glycoproteins of hog healthy and drug-intoxicated stomachs and of hog body fluids. AB - Naturally occurring glycoproteins have been extracted from fundic and antral mucosal tissue of the hog stomach by means of nondegrading techniques. Major and retarded glycoprotein fractions separated by gel filtration were further dissociated from appreciable amounts of noncovalently bound proteins by CsCl density gradient centrifugation. Antisera to glycoprotein fractions of fundic and antral regions of the stomach were prepared in rabbits. The major fractions from both gastric regions have similar molecular mass (approximately 2 x 10(6)), sedimentation coefficient (approximately 31.5 s), and specific viscosity (approximately 1.6). Purified fractions from each region were further separated into two subfractions by affinity chromatography on wheat germ lectin. Glycoprotein subfractions from antrum and fundus differ appreciably in their carbohydrate and amino acids content, share antigenic determinants, but do not cross-react with anti-hog serum protein antisera. Further diversity in native mucin glycoproteins was observed by the use of one-(D) and two-dimensional (2D) immunoelectrophoresis; subfractions that cross-react with specific anti-hog gastric glycoproteins were found to contain three or more components. D Immunoelectrophoretic analyses demonstrated (1) in vivo degradation of glycoprotein components of the major fundic fraction isolated from mucosal tissue of alcohol/acetyl salicylate-intoxicated hog stomachs and (2) in vitro catabolism of major fundic glycoproteins by corresponding mitochondrial lysosomal (ML) acid hydrolases. Furthermore, 2D-immunoelectrophoretic analyses showed that (1) hog synovial fluid and plasma proteins have similar prosthetic moieties as either reacted with anti-hog serum proteins antisera. Nonetheless, locations, shapes, and staining intensities of the immunoprecipitate lines differed, which is indicative of different structures of the carbohydrate moieties of components of synovial fluid and plasma proteins, and (2) only a minor fraction of hog cerebrospinal fluid cross-reacted with anti-hog serum protein antisera. This is contrary to the generally accepted deduction based on high-resolution 2D electrophoresis, indicative of different compositional patterns of plasma and cerebrospinal fluids. PMID- 8350383 TI - Percutaneous absorption of PCBs from soil: in vivo rhesus monkey, in vitro human skin, and binding to powdered human stratum corneum. AB - Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental pollutants. The major resident site for these PCBs is the soil, and human skin is frequently in contact with soil. Our objective was to determine the percutaneous absorption of the PCBs Aroclor 1242 and Aroclor 1254 from soil. PCB-contaminated soil was prepared at levels of 44 ppm Aroclor 1242 and 23 ppm Aroclor 1254. PCB concentrations on skin were 1.75 micrograms/cm2 for Aroclor 1242 and 0.91 microgram/cm2 for Aroclor 1254. In vivo percutaneous absorption in the rhesus monkey was determined by urinary and fecal [14C]-PCB excretion for a 5-wk period following topical dosing. Absorption of Aroclor 1242 was determined in vitro with human skin for comparative purposes. In vivo in the rhesus monkey the percutaneous absorption of Aroclor 1242 was 13.8 +/- 2.7 (SD)% of the dose and the absorption of Aroclor 1254 was 14.1 +/- 1.0%. These absorption amounts are similar to the absorption of Aroclor 1242 and 1254 from other vehicles (mineral oil, trichlorobenzene, acetone). With in vitro percutaneous absorption through human skin, most of the Aroclor 1242 and Aroclor 1254 resided in the skin and the amounts were dependent upon dosing vehicle (water > mineral oil > soil). Both PCBs readily partitioned from water into soil and human powdered stratum corneum. By difference the partitioning favored both PCBs going from soil into stratum corneum. These data emphasize the role of soil in percutaneous absorption and provide information for appropriate risk assessment. PMID- 8350384 TI - Toxicity of 1,1,1-trichloro-2-propanone in Sprague-Dawley rats. AB - 1,1,1-Trichloro-2-propanone (1,1,1-TCP) has been identified as a chlorination by product in finished drinking water supplies. Since little was known of its oral toxicity, exposure studies were conducted with male and female Sprague-Dawley rats (10 males and 10 females/group) exposed by corn oil gavage at 0, 16, 48, 161, or 483 mg/kg for 10 d or 0, 30, 90, or 270 mg/kg for 90 d. Evaluations included mortality, clinical signs, body weight, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, gross pathology, and histopathology. In the 10-d study, severe toxicity was observed at the highest dose level, since most treated animals (8/10 males and 7/10 females) died. Toxicity was also noted at 161 and 48 mg/kg. At 161 mg/kg, 2 males died and an increase in liver weights in both sexes was observed. Acanthosis and hyperkeratosis of the forestomach was present in males and females at 48 mg/kg and above. In the 90-d study, toxicity was significant at 270 mg/kg, with acanthosis and hyperkeratosis of the forestomach evident in most animals and ataxia in about one-half of them. Retinal degeneration, increased serum potassium, and increased blood urea nitrogen were present in females and increased blood calcium in males at that same dose level. Acanthosis and hyperkeratosis were observed in both sexes, and retinal degeneration was prominent in 2 females at 90 mg/kg. It was concluded that 16 mg/kg was the NOAEL (no observed adverse effect level) for the 10-d study while 30 mg/kg was the NOAEL for the 90-d exposure of Sprague-Dawley rats to 1,1,1,-trichloro-2 propanone. PMID- 8350385 TI - Down-regulation of muscarinic receptors and the m3 subtype in white-footed mice by dietary exposure to parathion. AB - The effect of ad libitum dietary exposure (as occurs in the field) to parathion for 14 d was investigated on the muscarinic acetylcholine receptor (mAChR) in brains and submaxillary glands of adults of a field species, the white-footed mouse Peromyscus leucopus. Immunoprecipitation using subtype selective antibodies revealed that the relative ratios of the m1-m5 mAChR subtypes in Peromyscus brain were similar to those in rat brain. There was little variability in acetylcholinesterase (AChE) activity in control mice brains but large variability in 39 exposed mice, resulting from differences in food ingestion and parathion metabolism. Accordingly, data on radioligand binding to mAChRs in each mouse brain were correlated with brain AChE activity in the same mouse, and AChE inhibition served as a biomarker of exposure reflecting in situ paraoxon concentrations. Exposure to parathion for 14 d reduced maximal binding (Bmax) of [3H]quinuclidinyl benzilate ([3H]QNB), [3H]-N-methylscopolamine ([3H]NMS), and [3H]-4-diphenylacetoxy-N-methylpiperidine methiodide ([3H]-4-DAMP) by up to approximately 58% without affecting receptor affinities for these ligands. Maximal reduction in Bmax of [3H]QNB and [3H]-4-DAMP binding occurred in mice with highest AChE inhibition, while equivalent maximal reduction in Bmax of [3H]NMS occurred in mice with only approximately 10% AChE inhibition, without further change at higher parathion doses. This is believed to be due to the hydrophilicity of [3H]NMS, which limits its accessibility to internalized desensitized receptors. In submaxillary glands (mAChRs are predominantly m3 subtype), there were significant dose-dependent reductions in [3H]QNB binding and m3 mRNA levels in exposed mice, revealed by Northern blot analyses. The reduction in m3 receptors is suggested to result mostly from reduced synthesis at the transcription level, rather than from translational or posttranslational events. The data suggest that down-regulation of mAChRs occurs after dietary exposure for 14 d to sublethal concentrations of parathion in a field rodent species, and that significant though incomplete recovery in AChE and mAChRs occurs in 7 d following termination of exposure. PMID- 8350386 TI - 110/140 laminin-binding protein immunoreactivity in spinal dorsal root ganglia: a capsaicin-insensitive reduction induced by constriction injury of the sciatic nerve in rats. AB - The distribution of 110/140 laminin-binding protein (110/140 LBP) in the spinal dorsal root ganglia (DRG) and its regulation by partial constriction of the sciatic nerve was studied in adult rats. The cross-sectional area of neurons with 110/140 LBP-immunoreactivity (-I) showed an approximately normal frequency distribution. The 110/140 LBP-I was observed in neuronal cell bodies exclusive of the nucleus. Following sciatic nerve constriction, the 110/140 LBP-I was downregulated in the ipsilateral L4-5 DRG. DRG neurons with a cross-sectional area > or = 1600 microns 2 were preferentially affected. Neonatal capsaicin treatment, a procedure that selectively destroys a subpopulation of DRG neurons with fine unmyelinated axons, had no effect on the reduction of 110/140 LBP in the DRG induced by sciatic nerve constriction. Western immunoblot analysis confirmed a reduction of 110/140 LBP on the side ipsilateral to the constriction. These results demonstrate a LBP within primary sensory neurons and its suppression by peripheral nerve injury. The data support a role for LBP in the adult nervous system. PMID- 8350387 TI - Microtubule-associated protein MAP1B expression precedes the morphological differentiation of oligodendrocytes. AB - The microtubule-associated protein MAP1B is believed to play an important role in the outgrowth of neurites from neurons (Tucker and Matus, Dev Biol 130: 423-434, 1988). We have investigated the possibility that MAP1B might participate in the formation of processes in cultured oligodendrocytes by an analysis of the expression of MAP1B during oligodendrocyte progenitor development. The appearance of the antigens recognized by the monoclonal antibodies A2B5, O4, and O1 which define distinct stages in the maturation of progenitors, was compared with the developmental expression of MAP1B. MAP1B is first detectable in O4+ preoligodendrocytes prior to the acquisition of galactocerebroside and immediately before they develop the complex process-bearing morphology characteristic of terminally differentiated myelin-forming oligodendrocytes in the CNS. In contrast, astrocytes have negligible amounts of MAP1B. These results demonstrate that the expression of MAP1B precedes the development of the mature oligodendrocyte phenotype and suggest that interactions between microtubules and MAP1B might have a role in the formation and stabilization of myelin-forming processes. PMID- 8350388 TI - Testosterone regulation of the regenerative properties of injured rat sciatic motor neurons. AB - We have previously demonstrated that systemic administration of testosterone differentially regulates the regenerative properties of injured hamster facial motor neurons, which are androgen receptor-containing cranial motor neurons. In this investigation, the hypothesis that testosterone alters the regenerative properties of rat sciatic motor neurons, which are androgen receptor-containing spinal motor neurons, was tested using fast axonal transport of radioactively labeled proteins to assess sciatic nerve regeneration. Adult castrated male rats were subjected to crush axotomy of the sciatic nerve at the level of the gemelli tendons (mid-thigh). One-half of the axotomized animals received subcutaneous implants of testosterone propionate (TP), with the remainder of the animals sham implanted with blank capsules. The outgrowth distances of the leading axons were measured at 5, 6, 7, and 11 days postoperative. Linear regression analysis was accomplished, with the slope of the line representing the regeneration rate and the x-intercept the initial delay of sprout formation. Systemic administration of testosterone resulted in a 13% increase in the rate of regeneration, relative to the control, -TP group. Outgrowth distances were significantly increased in the +TP group only in the later stages of regeneration. However, TP did not shorten the delay in sprout formation in regenerating sciatic motor neurons, but instead produced a small prolongation in the delay time. This pattern of hormonal regulation of the regenerative properties of spinal motoneurons is similar to that previously found in cranial motoneurons. The prolongation of the initial delay may have been a factor in the lack of significant outgrowth distances during the early stages of regeneration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350389 TI - Glial progenitor cells of the nerve fiber layer of the olfactory bulb: effect of astrocyte growth media. AB - There are two morphologically distinct types of glial cells (i.e., ensheathing cells and astrocytes) in the nerve fiber layer (NFL) of the adult mammalian olfactory bulb. Ensheathing cells provide ensheathment for olfactory axons, whereas astrocytes occupy the interfascicular spaces of the olfactory NFL. During embryonic development, however, only one type of glial cell is found in this layer of the olfactory bulb, namely, the ensheathing cell. Even though ensheathing cells take up residence within the CNS, they are actually derived from the olfactory placode. Far less is known about the developmental origin of interfascicular astrocytes, which arise either from the glial progenitor cells that give rise to ensheathing cells or from astrocyte precursor cells that migrate into the NFL from deeper layers of the bulb primordium. In the present study, enriched populations of ensheathing cells were grown in vitro in media known to promote the growth and differentiation of astrocytes to determine whether ensheathing cell progenitors could differentiate into astrocytes. These media failed to induce the appearance of astrocytes in the ensheathing cell cultures. It was concluded that the astrocytes of the NFL most likely arise from progenitor cells that migrate into this layer from deeper parts of the developing bulb. PMID- 8350390 TI - Protease production by cultured microglia: substrate gel analysis and immobilized matrix degradation. AB - The production of collagen-degrading proteases by cultured neonatal rat microglia was examined using an immobilized fibronectin-gelatin matrix coupled to a fluorescent marker and by substrate gel analysis. When microglia were plated onto the surface of the matrix and incubated under resting (nonstimulated) conditions, a small but visible amount of immobilized matrix was degraded. Treatment with lipopolysaccharide (LPS) or interleukin-1 (IL-1) significantly increased the number of microglia demonstrating substrate degradation. Substrate-SDS polyacrylamide gel electrophoresis of samples of supernatants from untreated cultured microglia indicated the presence of a 72 and a 92 kD metalloproteinase with characteristics corresponding to collagenases. Supernatants from untreated astrocyte cultures were shown to have primarily a 72 kD metalloproteinase. Proteinase activity increased on stimulation of the microglia with LPS and IL-1 in a dose-dependent fashion. These results indicate that cultured microglia release active proteases capable of degrading the extracellular matrix in a localized region. The production of proteases by activated microglia may have important physiological and pathophysiological consequences within the restricted extracellular matrix of the CNS. PMID- 8350391 TI - Interleukin-2 as a neurotrophic factor for supporting the survival of neurons cultured from various regions of fetal rat brain. AB - Interleukin(IL)-2 supported the survival and enhanced neurite extension of cultured hippocampal neurons prepared from embryonic 18-day-old rats. This neurotrophic effect was observed at concentrations of 2 to 200 U/ml, and almost all the neurons could survive for more than 2 days in the presence of 200 U/ml of IL-2. This viability-promoting effect of IL-2 on the neurons was completely blocked with anti-IL-2 antibodies. IL-2 also supported the survival of cultured cortical, striatal, and septal neurons. These results indicate that IL-2 has a survival-promoting effect on a wide variety of neurons. On the other hand, IL-2 did not affect the choline acetyltransferase (ChAT) activity of striatal neurons, suggesting that this cytokine does not act as a differentiation factor for striatal cholinergic neurons. PMID- 8350392 TI - Acylation of lysophosphatidylcholine by brain membranes. AB - Brain microsomes catalyze the acylation of lysophosphatidylcholine (lysoPtdCho) in the presence and absence of added CoA derivatives. The catalytic activity is distributed widely in various subcellular fractions from rat or bovine cerebral cortex as measured by the conversion of 1-[14C]palmitoyl-sn-glycero-3 phosphocholine to [14C]PtdCho. Analysis of this latter compound revealed that the dipalmitoyl derivative is the predominant molecular species, which is formed in this reaction by transacylation between two [14C]lysoPtdCho molecules. This lysoPtdCho: lysoPtdCho transacylation reaction was enhanced several-fold by the addition of oleoyl-CoA, which also is an effective donor of acyl groups in the acyl-CoA: lysoPtdCho acyltransferase-catalyzed reaction. Measurements of the initial velocity of the transacylation reaction were used to determine kinetic constants. Apparent Km values for lysoPtdCho in the presence and absence of oleoyl-CoA were 29 microM and 104 microM, respectively, and the corresponding maximal velocities were 0.11 and 1.06 nmol.min-1.mg-1, respectively. Oleoyl-CoA at 4 microM produced half-maximal stimulation of the transacylation reaction. CoA also stimulated the rate of conversion of [14C]lysoPtdCho to [14C]PtdCho, either in the presence or absence of oleoyl-CoA, with a half-maximal effect of CoA at 80 microM. These results may be important in understanding the regulation of PtdCho synthesis and the mechanism by which acyl group composition of this compound is controlled. PMID- 8350393 TI - Axon growth is enhanced by NCAM lacking the VASE exon when expressed in either the growth substrate or the growing axon. AB - The neural cell adhesion molecule NCAM exists as several related peptides formed by alternative splicing of the single NCAM gene. Here the ability of NCAM containing and lacking the alternatively spliced VASE exon to act as a permissive growth substrate was tested by examining retinal axon outgrowth on normal L cell fibroblasts and L cells expressing stably transfected 140 kD NCAM +/- VASE. L cells expressing either NCAM form were a more permissive substrate than control L cells. At higher substrate cell densities, greater axon outgrowth occurred on substrate cells expressing NCAM - VASE than on those expressing NCAM + VASE. Similar experiments tested retinal axon growth on neuronal substrates by utilizing clonal B35 cells, C3 cells that are NCAM lacking variants of B35, and C3 cells into which 140 kD NCAM +/- VASE has been restored by transfection. Axon growth on C3 cells transfected with NCAM - VASE was greater than that on all other substrates including cells transfected with NCAM + VASE. In these experiments C3 cells and transfected C3 expressing NCAM + VASE cell promoted similar outgrowth. The influence on neurite growth of the NCAM isoform of the neurite itself was tested by examining neurite formation using combinations of C3 cells and C3 NCAM transfectants both in the growth monolayer and as responding cells. C3 cells were able to extend neurites, indicating NCAM is not required for neurite growth. However, C3 derivatives transfected with NCAM +/- VASE had greater neurite outgrowth. The most extensive neurite growth was found when NCAM VASE was expressed by both substrate cells and the responding neurite growing cells. Thus NCAM enhances axon or neurite outgrowth when present either in the growth substrate or on the growing axon. NCAM - VASE has a significantly greater growth promoting capability than NCAM + VASE. The expression of NCAM + VASE by more mature neural cells could thus be a significant factor in the reduced axonation capabilities of mature neurons. PMID- 8350394 TI - Assembly and composition of intracellular particles formed by Moloney murine leukemia virus. AB - Assembly of type C retroviruses such as Moloney murine leukemia virus (M-MuLV) ordinarily occurs at the plasma membranes of infected cells and absolutely requires the particle core precursor protein, Pr65gag. Previously we have shown that Pr65gag is membrane associated and that at least a portion of intracellular Pr65gag protein appears to be routed to the plasma membrane by a vesicular transport pathway. Here we show that intracellular particle formation can occur in M-MuLV-infected cells. M-MuLV immature particles were observed by electron microscopy budding into and within rough endoplasmic reticulum, Golgi, and vacuolar compartments. Biochemical fractionation studies indicated that intracellular Pr65gag was present in nonionic detergent-resistant complexes of greater than 150S. Additionally, viral RNA and polymerase functions appeared to be associated with intracellular particles, as were Gag-beta-galactosidase fusion proteins which have the capacity to be incorporated into virions. Immature intracellular particles in postnuclear lysates could be proteolytically processed in vitro to mature forms, while extracellular immature M-MuLV particles remained immature as long as 10 h during incubations. The occurrence of M-MuLV-derived intracellular particles demonstrates that Pr65gag can associate with intracellular membranes and indicates that if a plasma membrane Pr65gag receptor exists, it also can be found in other membrane compartments. These results support the hypothesis that intracellular particles may serve as a virus reservoir during in vivo infections. PMID- 8350395 TI - Mutations that alter an Arg-Gly-Asp (RGD) sequence in the adenovirus type 2 penton base protein abolish its cell-rounding activity and delay virus reproduction in flat cells. AB - The adenovirus penton base protein has a cell rounding activity and may lyse endosomes during virus entry into the cytoplasm. We found that penton base that was expressed in Escherichia coli also caused cell rounding and that cells adhered to polystyrene wells that were coated with the protein. Mutant analysis showed that both properties required an Arg-Gly-Asp (RGD) sequence at residues 340 to 342 of penton base. In flat adherent cells, virus mutants with amino acid substitutions in the RGD sequence were delayed in virus reproduction and in the onset of viral DNA synthesis. In nonadherent or poorly spread cells, the kinetics of mutant virus reproduction were similar to those of wild-type adenovirus type 2. Expression of the mutant phenotype exclusively in the flat cells that we tested supports a model in which penton base interacts with an RGD-directed cell adhesion molecule during adenovirus uptake or uncoating. PMID- 8350397 TI - Identification, sequence, and transcriptional mapping of lef-3, a baculovirus gene involved in late and very late gene expression. AB - A trans-acting gene required for late viral gene expression in transient expression assays was identified in the genome of Autographa californica nuclear polyhedrosis virus. A genomic library of A. californica nuclear polyhedrosis virus DNA lacking a clone spanning the region from 43 to 48 map units (mu) was unable to activate gene expression from a reporter plasmid when the reporter gene was driven by a baculovirus late or very late promoter in transient expression assays. The genomic region responsible for activating reporter gene expression was further mapped to 43.4 to 45.2 mu of the viral genome. The nucleotide sequence of this region was determined and shown to contain several small open reading frames (ORFs) and one major ORF, named lef-3, for late expression factor 3. The lef-3 ORF was predicted to encode a polypeptide of 385 amino acids and with a molecular mass of 44,529 daltons. No homolog to the lef-3 ORF was found in existing data bases. Further analysis showed that only the lef-3 ORF in the region from 43.4 to 45.2 mu was necessary for late gene activation in the assays used. The temporal regulation of lef-3 transcription was studied by Northern (RNA) blot hybridization; lef-3 was found to be an early gene that was transcribed primarily as a 2.0-kb mRNA. Primer extension analysis and S1 nuclease protection assays revealed that lef-3 transcription initiated about 280 bp upstream of the first ATG codon and terminated near a polyadenylation signal, 130 bp downstream of the last codon of the lef-3 ORF. PMID- 8350396 TI - Large E1B proteins of adenovirus types 5 and 12 have different effects on p53 and distinct roles in cell transformation. AB - The formation of complexes between oncoproteins of DNA tumor viruses and the cellular protein p53 is thought to result in inactivation of the growth suppressor function of p53. In cells transformed by nononcogenic human adenovirus type 5 (Ad5), the 55-kDa protein encoded by E1B forms a stable complex with p53 and sequesters it in the cytoplasm. However, the homologous 54-kDa protein of highly oncogenic Ad12 does not detectably associate with p53. Yet in Ad12 transformed cells, p53 is metabolically stable, is present at high levels in the nucleus, and contributes to the oncogenicity of the cells. Such properties have previously been described for mutant forms of p53. Here, we show that stable p53 in Ad12-transformed cells is wild type rather than mutant and that stabilization of p53 is a direct consequence of the expression of the Ad12 E1B protein. We also compared the effects of the E1B proteins on transformation of rodent cells by different combinations of oncogenes. A synergistic interaction was observed for the gene encoding the 54-kDa E1B protein of Ad12 with myc plus ras oncogenes, resembling the effect of mutant p53 on myc plus ras. In contrast, the Ad5 55-kDa E1B protein strongly inhibited transformation by myc plus ras but stimulated transformation by E1A plus ras. The data are explained in terms of different interactions of the two E1B proteins with endogenous p53. The results suggest that in cultured rat cells, endogenous wild-type p53 plays an essential role in cell proliferation, even in the presence of myc plus ras. The dependence on p53 is lost, however, when the adenovirus E1A oncogene is present. PMID- 8350399 TI - Effects of the tom1 mutation of Arabidopsis thaliana on the multiplication of tobacco mosaic virus RNA in protoplasts. AB - For the multiplication of RNA viruses, specific host factors are considered essential, but as of yet little is known about this aspect of virus multiplication. To identify such host factors, we previously isolated PD114, a mutant of Arabidopsis thaliana, in which the accumulation of the coat protein of tobacco mosaic virus (TMV) in uninoculated leaves of an infected plant was reduced to low levels. The causal mutation, designated tom1, was single, nuclear, and recessive. Here, we demonstrate that the tom1 mutation affects the amplification of TMV-related RNAs in a single cell. When protoplasts were inoculated with TMV RNA by electroporation, the percentage of TMV-positive protoplasts (detected by indirect immunofluorescence staining with anti-TMV antibodies) was lower (about 1/5 to 1/10) among PD114 protoplasts than among wild type protoplasts. In TMV-positive PD114 protoplasts, the amounts of the positive strand RNAs (the genomic RNA and subgenomic mRNAs) and coat protein reached levels similar to, or slightly lower than, those reached in TMV-positive wild type protoplasts, but the accumulation of the positive-strand RNAs and coat protein occurred more slowly than with the wild-type protoplasts. The parallel decrease in the amounts of the coat protein and its mRNA suggests that the coat protein is translated from its mRNA with normal efficiency. These observations support the idea that the TOM1 gene encodes a host factor necessary for the efficient amplification of TMV RNA in an infected cell. Furthermore, we show that TMV multiplication in PD114 protoplasts is severely affected by the coinoculation of cucumber mosaic virus (CMV) RNA. When PD114 protoplasts were inoculated with a mixture of TMV and CMV RNAs by electroporation, the accumulation of TMV-related molecules was approximately one-fifth of that in PD114 protoplasts inoculated with TMV RNA alone. No such reduction in the accumulation of TMV-related molecules was observed when wild-type protoplasts were inoculated with a mixture of TMV and CMV RNAs or when wild-type and PD114 protoplasts were inoculated with a mixture of TMV and turnip crinkle virus RNAs. These observations are compatible with a hypothetical model in which a gene(s) that is distinct from the TOM1 gene is involved in both TMV and CMV multiplication. PMID- 8350398 TI - Deletion mutation analysis of the adenovirus type 2 E3-gp19K protein: identification of sequences within the endoplasmic reticulum lumenal domain that are required for class I antigen binding and protection from adenovirus-specific cytotoxic T lymphocytes. AB - Adenovirus E3-gp19K is a transmembrane glycoprotein, localized in the endoplasmic reticulum (ER), which forms a complex with major histocompatibility complex (MHC) class I antigens and retains them in the ER, thereby preventing cytolysis by cytotoxic T lymphocytes (CTL). The ER lumenal domain of gp19K, residues 1 to 107, is known to be sufficient for binding to class I antigens; the transmembrane and cytoplasmic ER retention domains are located at residues ca. 108 to 127 and 128 to 142, respectively. To identify more precisely which gp19K regions are involved in binding to class I antigens, we constructed 13 in-frame virus deletion mutants (4 to 12 amino acids deleted) in the ER lumenal domain of gp19K, and we analyzed the ability of the mutant proteins to form a complex with class I antigens, retain them in the ER, and prevent cytolysis by adenovirus-specific CTL. All mutant proteins except one (residues 102 to 107 deleted) were defective for these properties, indicating that the ability of gp19K to bind to class I antigens is highly sensitive to mutation. All mutant proteins were stable and were retained in the ER. Sequence comparisons among adenovirus serotypes reveal that the ER lumenal domain of gp19K consists of a variable region (residues 1 to 76) and a conserved region (residues 77 to 98). We show, using the mutant proteins, that the gp19K-specific monoclonal antibody Tw1.3 recognizes a noncontiguous epitope in the variable region and that disruption of the variable region by deletion destroys the epitope. The monoclonal antibody and class I antigen binding results, together with the serotype sequence comparisons, are consistent with the idea that the ER lumenal domain of gp19K has three subdomains that we have termed the ER lumenal variable domain (residues 1 to ca. 77 to 83), the ER lumenal conserved domain (residues ca. 84 to 98), and the ER lumenal spacer domain (residues 99 to 107). We suggest that the ER lumenal variable domain of gp19K has a specific tertiary structure that is important for binding to the polymorphic alpha 1 and alpha 2 domains of class I heavy (alpha) chains. We suggest that the ER lumenal conserved domain of gp19K may interact with some conserved protein, perhaps the highly conserved alpha 3 domain of class I heavy chains. Finally, the ER lumenal spacer domain may allow the ER lumenal variable and conserved domains to extend out from the ER membrane so that they can interact with class I heavy chains. PMID- 8350400 TI - Reovirus M2 gene is associated with chromium release from mouse L cells. AB - In this study, we investigated the interaction of reovirus particles with cell membranes by using a 51Cr release assay. We confirmed prior observations (J. Borsa, B. D. Morash, M. D. Sargent, T. P. Copps, P. A. Lievaart, and J. G. Szekely, J. Gen. Virol. 45:161-170, 1979) that intermediate subviral particles (ISVPs) of reovirus type 3 strain Abney (T3A) induced the release of 51Cr from preloaded L cells and showed that the intact virion and core forms did not. Reovirus type 1 strain Lang (T1L) ISVPs were found to be less efficient at 51Cr release than T3A ISVPs. Reassortants between these strains indicated that the 51Cr release phenotype segregates with the M2 gene segment. Biochemical studies indicated that the ISVPs' acquisition of the capacity to induce 51Cr release followed the cleavage of the viral M2 gene product mu 1/mu 1C to fragments delta and phi during virion conversion to ISVP but did not directly correlate with this cleavage. These studies suggest that the reovirus M2 gene product (in its cleaved form) plays a role in interacting with cell membranes. PMID- 8350401 TI - A new regulatory element that augments the Tax-dependent enhancer of human T-cell leukemia virus type 1 and cloning of cDNAs encoding its binding proteins. AB - The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) trans activates the 21-bp enhancer of HTLV-1. A sequence of more than two copies of the 21-bp enhancer is efficiently activated by Tax, but one copy is not activated extensively. Another sequence (TRE-2, positions -163 to -117) adjacent to the 21 bp enhancer in the long terminal repeat of HTLV-1 can enhance a single copy of the 21-bp enhancer activity in trans activation by Tax. This sequence contains motifs related to the Ets- and NF-kappa B-binding sequences, but mutations at these sites indicated that neither is responsive to cooperation with the 21-bp enhancer. A deletion mutation of TRE-2 identified 25 bases at positions -158 to 134 (TRE-2S) as an essential sequence, and TRE-2S was sufficient to give maximum cooperation with one copy of the 21-bp enhancer in trans activation by Tax protein. Using TRE-2S as a probe, we screened a cDNA library of HUT102 cells by the Southwestern (DNA-protein) procedure and isolated two cDNA clones, THP-1 and 2. These two clones encode TRE-2S-binding proteins, and they differ by only an extra 17 amino acids in THP-2. Both THP proteins contain five zinc finger motifs which are strikingly similar to those of the GLI family, an amplified gene product in glyoma cells. The binding site of THP-1 and -2 was GAACCACCCA in TRE 2S, which is highly homologous to the GLI-binding site. These results suggest that binding of THP to TRE-2S may be involved in cooperation with one copy of the 21-bp enhancer in responding to Tax trans activation. PMID- 8350402 TI - Reactivation of transcription from a vaccinia virus early promoter late in infection. AB - We have studied the kinetics of RNA synthesis from the vaccinia virus 7,500 molecular-weight gene (7.5K gene) which is regulated by early and late promoters arranged in tandem. Unexpectedly, after a first burst of RNA synthesis early in infection, transcription was reactivated late in infection. Reactivation was not dependent on the location of the promoter in the genome or on the presence of the upstream late regulatory sequences. The mRNA synthesized from the reactivated promoter in the late phase had the same 5' and 3' ends as the molecules transcribed in the early phase. Interestingly, these molecules were efficiently translated despite the absence of the poly(A) leader characteristic of late mRNAs. Reactivation appears to be dependent on virus assembly since it is prevented by rifampin, a specific inhibitor of morphogenesis. Finally, analysis of various other early genes showed that reactivation is not unique to the 7.5K early promoter. PMID- 8350403 TI - Hepatitis B virus genotype A rarely circulates as an HBe-minus mutant: possible contribution of a single nucleotide in the precore region. AB - The emergence of HBe-minus hepatitis B virus (HBV) mutants, usually through a UAG nonsense mutation at codon 28 of the precore region, helps the virus to survive the anti-HBe immune response of the host. Host and viral factors that predispose to the emergence of such mutants are not well characterized. The fact that the precore region forms a hairpin structure essential for the packaging of viral pregenomic RNA may explain the extremely high prevalence of the UAG mutation at codon 28. It converts a wobble U-G pair in the packaging signal between nucleotide 3 of codon 15 (CCU) and nucleotide 2 of codon 28 (UGG) into a U-A pair. Since genotype A of HBV has a CCC sequence at codon 15, the UAG mutation would, instead, disrupt a C-G pair present in the wild-type virus. This alteration was shown by transfection experiments to greatly compromise the packaging of pregenomic RNA. The implication of this finding was elucidated by molecular epidemiological studies. Genotype A was found to be the most prevalent genotype in the wild-type virus populations in France but was found in only 1 of the 46 isolates of HBe-minus mutants found there. These mutants were contributed chiefly by genotype D, the second most prevalent genotype in France, which is characterized by a CCU sequence at codon 15. The role of the single nucleotide at codon 15 was confirmed by the finding of the single genotype A isolate in which both wild-type and mutant viruses were present. Interestingly, nearly all of the mutants had a codon 15 sequence of CCU instead of the CCC present in the wild type viruses. Our results suggest that genotype A of HBV rarely circulates as HBe minus mutants, probably because of a requirement for a simultaneous sequence change at codon 15. These data, together with the virtual absence of genotype A in the Chinese samples examined, may provide some insights into the uneven prevalence of HBe-minus mutants in the world. PMID- 8350404 TI - Glycoprotein E1 of hog cholera virus expressed in insect cells protects swine from hog cholera. AB - The processing and protective capacity of E1, an envelope glycoprotein of hog cholera virus (HCV), were investigated after expression of different versions of the protein in insect cells by using a baculovirus vector. Recombinant virus BacE1[+] expressed E1, including its C-terminal transmembrane region (TMR), and generated a protein which was similar in size (51 to 54 kDa) to the size of E1 expressed in swine kidney cells infected with HCV. The protein was not secreted from the insect cells, and like wild-type E1, it remained sensitive to endo-beta N-acetyl-D-glucosaminidase H (endo H). This indicates that E1 with a TMR accumulates in the endoplasmic reticulum or cis-Golgi region of the cell. In contrast, recombinant virus BacE1[-], which expressed E1 without a C-terminal TMR, generated a protein that was secreted from the cells. The fraction of this protein that was found to be cell associated had a slightly lower molecular mass (49 to 52 kDa) than wild-type E1 and remained endo H sensitive. The high-mannose units of the secreted protein were trimmed during transport through the exocytotic pathway to endo H-resistant glycans, resulting in a protein with a lower molecular mass (46 to 48 kDa). Secreted E1 accumulated in the medium to about 30 micrograms/10(6) cells. This amount was about 3-fold higher than that of cell-associated E1 in BacE1[-] and 10-fold higher than that of cell-associated E1 in BacE1[+]-infected Sf21 cells. Intramuscular vaccination of pigs with immunoaffinity-purified E1 in a double water-oil emulsion elicited high titers of neutralizing antibodies between 2 and 4 weeks after vaccination at the lowest dose tested (20 micrograms). The vaccinated pigs were completely protected against intranasal challenge with 100 50% lethal doses of HCV strain Brescia, indicating that E1 expressed in insect cells is an excellent candidate for development of a new, safe, and effective HCV subunit vaccine. PMID- 8350405 TI - Maturation of dimeric viral RNA of Moloney murine leukemia virus. AB - We have analyzed the dimeric RNA present in Moloney murine leukemia virus (MoMuLV) particles. We found that the RNA in newly released virions is in a conformation different from that in mature virions, since it has a different electrophoretic mobility in nondenaturing agarose gels and dissociates into monomers at a lower temperature. On the basis of these results, we suggest that the RNA initially packaged into nascent virions is already dimeric but that the dimer undergoes a maturation process after the virus is released from the cell. In further experiments, we tested the possibility that this maturation event is linked to the maturation cleavage of the virion proteins, which is catalyzed by the viral protease (PR). We found that the dimeric RNA isolated from PR- mutant virions resembles that from immature virions: it has a lower electrophoretic mobility and a lower sedimentation rate, and it also dissociates at a lower temperature than does RNA from mature wild-type virions. When Kirsten sarcoma virus is rescued by a PR- mutant or by a somewhat leaky cysteine array mutant of MoMuLV, its RNA also exhibits a electrophoretic mobility lower than that in the wild-type pseudotype. These results suggest that the maturation of dimeric RNA in released virus particles requires the cleavage of the Gag precursor and the presence of an intact cysteine array in the released nucleocapsid protein. PMID- 8350406 TI - Inhibition of African swine fever virus binding and infectivity by purified recombinant virus attachment protein p12. AB - The African swine fever virus protein p12, involved in virus attachment to the host cell, has an apparent molecular mass of 17 kDa in sodium dodecyl sulfate polyacrylamide gel electrophoresis under nonreducing conditions. We have also identified 12- and 10-kDa forms of the p12 protein in infected Vero cells and found that the mature 17-kDa protein is the only form present in virus particles. The p12 protein has been produced in large amounts in Spodoptera frugiperda insect cells infected with a recombinant baculovirus. A 17-kDa protein that possessed the biological properties of the viral protein was produced, since it bound to susceptible Vero cells and not to receptor-negative L cells, which do not support virus replication. The binding of the baculovirus-expressed protein p12 to Vero cells was specifically blocked by virus particles. In addition, the recombinant protein purified by immunoaffinity chromatography blocked the specific binding of virus particles to susceptible cells and prevented infection, demonstrating that the p12 protein mediates the attachment of virions to specific receptors and indicating that blocking the p12-mediated interaction between African swine fever virus and receptors in Vero cells can inhibit infection. However, although antibodies specific for protein p12 are induced in natural infections and in animals inoculated with inactivated virus or recombinant protein p12, these antisera did not inhibit virus binding to the host cell or neutralize virus infectivity. PMID- 8350407 TI - Sequences responsible for the distinctive hemolytic potentials of Friend and Moloney murine leukemia viruses are dispersed but confined to the psi-gag-PR region. AB - Friend and Moloney murine leukemia viruses (F- and M-MuLV) induce distinct diseases in hematopoietic tissues following inoculation of newborn mice of susceptible strains. F-MuLV induces erythroleukemia preceded by severe early hemolytic anemia; M-MuLV induces thymomas and only very mild hemolysis. The major viral determinant of severe early hemolytic anemia residues in the env gene, but sequences located outside this gene can modulate this effect. By means of genetic chimeras of F- and M-MuLV, we have found that although they are confined to the 5' portion of the env gene intron, sequences that determine the distinctive hemolytic potentials of F- and M-MuLV are widely distributed over a region spanning the RNA encapsidation domain, the gag gene, and the portion of the pol gene encoding the viral protease. Within this large region, two fragments of M MuLV, a 1.3-kb region encoding the matrix, pp12, and capsid proteins and a 0.8-kb region encoding the nucleocapsid and the viral protease, were capable, individually, of partially attenuating the capacity of F-MuLV for induction of severe early hemolytic anemia. In association, these two fragments conferred complete attenuation. Moreover, a second pair of adjacent fragments within this large region appeared to behave cooperatively to confer complete attenuation; a 0.36-kb region roughly corresponding to the encapsidation domain, although not detectably altering hemolytic potential on its own, deepened the attenuation conferred by the adjacent 1.3-kb region. Whether capable of inducing severe early hemolytic anemia or not and despite different efficiencies of induction of recombinant polytropic viruses, all chimeric viruses retained the erythroleukemogenicity of the F-MuLV parent. PMID- 8350409 TI - Sindbis virus membrane fusion is mediated by reduction of glycoprotein disulfide bridges at the cell surface. AB - We have examined the role of thiol-disulfide exchange reactions during the penetration of cells by Sindbis virus. The protein-protein association that form the rigid icosahedral lattice of the Sindbis virus envelope have been shown to be stabilized by disulfide bridges, and reduction of these critical disulfide bridges during cell penetration may be the mechanism by which the rigid protein lattice is disrupted prior to fusion (R. Anthony and D. T. Brown, J. Virol. 65:1187-1194, 1991; R. Anthony, A. Paredes, and D. T. Brown, Virology 190:330 336, 1992). Reduction of disulfide bridges occurs at near neutral pHs via thiol disulfide exchange reactions, and these reactions can be blocked by covalent modification of the thiol involved. In this study, the effects of the reducing agent 2-mercaptoethanol on Sindbis virus-mediated cell-cell fusion from without and the effects of the membrane-impermeable thiol-alkylating reagent 5,5' dithiobis(2-nitrobenzoic acid) on Sindbis virus penetration were determined. The presence of exogenous reducing agent was found to induce fusion from without under conditions unfavorable to both typical Sindbis virus-mediated fusion from without and cysteine-mediated thiol-disulfide exchange reactions. In addition, the thiol-alkylating reagent was found to inhibit Sindbis virus entry when present during infection. These results are consistent with a model for Sindbis virus entry in which reduction of critical disulfide bridges at the cell surface disrupts the rigid protein-protein associations of the envelope, allowing membrane fusion and release of the viral genome into the cell. PMID- 8350408 TI - Transformation by the fos or jun oncogene does not increase AP-1 DNA-binding activity. AB - The c-fos and c-jun proto-oncogenes encode components of the transcription factor AP-1. To determine whether transformation by the v-fos or v-jun oncogene results in alterations in the level or regulation of this factor, we have characterized AP-1 DNA-binding activity in nuclear extracts prepared from v-fos- and c-fos transformed rat fibroblast cell lines and v-jun-transformed chicken embryo fibroblasts under various growth conditions. During proliferation, the level of AP-1 DNA-binding activity does not differ among the v-fos, c-fos, or v-jun transformed cells and their normal progenitors, despite constitutive overexpression of the corresponding oncoproteins. Therefore, although necessary, it is not likely that an increase in DNA binding is sufficient for fos or jun transformation. Normal rat and chicken fibroblasts demonstrate very low levels of AP-1 DNA-binding activity when quiescent, and upon serum stimulation a biphasic increase is observed. A similar cyclical pattern is seen in v-fos-transformed cells, but in v-jun-transformed cells AP-1 DNA-binding activity does not fluctuate in response to serum stimulation, which suggests that this level of control may be exerted through the Jun component of the AP-1 complex. PMID- 8350410 TI - Activation of the human T-cell leukemia virus type I enhancer is mediated by binding sites for Elf-1 and the pets factor. AB - Infection with human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell lymphoma/leukemia. This disease occurs in only a small minority of people infected with HTLV-I and manifests itself many years after infection. Therefore, it appears that a fine balance exists between HTLV-I and the host T cell factors with which it interacts. HTLV-I encodes a transactivating protein, Tax, which activates viral transcription via cellular mechanisms which are incompletely understood. As viral gene expression is negligible during latency, it is doubtful that Tax controls the initial transition to the replicative state. Tax-independent cellular factors which control HTLV-I transcription, and presumably latency, have received little study. Recently, the product of the chicken proto-oncogene ets-1 has been shown to bind to the HTLV-I enhancer and modestly activate transcription in certain cell types (S. C. Gitlin, R. Bosselut, A. Gegonne, J. Ghysdael, and J. N. Brady, J. Virol. 65:5513-5523, 1991). However, the functional significance of the ets-binding site in the intact enhancer has not previously been shown. We now demonstrate that site-specific mutation of the purine-rich ets-binding site significantly diminishes inducible enhancer function, but not Tax response, in the human Jurkat T-cell line. Similarly, mutation of the peri-ets (pets) site, not previously noted in the HTLV-I enhancer, markedly inhibits inducible enhancer function but not Tax response. Further, we show that the predominant protein binding the purine-rich HTLV-I enhancer element in human T cells is not ets-1 but Elf-1, a member of the ets family which is very similar to the Drosophila morphogen E74. Regulation of HTLV I through Elf-1/pets enhancer motifs resembles that seen with human immunodeficiency virus type 2 (D. M. Markovitz, M. Smith, J. Hilfinger, M. C. Hannibal, B. Petryniak, and G. J. Nabel, J. Virol. 66:5479-5484, 1992; J. M. Leiden, C.-W. Wang, B. Petryniak, M. Smith, D. M. Markovitz, G. J. Nabel, and C. B. Thompson, J. Virol. 66:5890-5897, 1992), another human pathogenic retrovirus with a relatively long incubation period. PMID- 8350411 TI - Human immunodeficiency virus type 1 Vpu protein induces degradation of chimeric envelope glycoproteins bearing the cytoplasmic and anchor domains of CD4: role of the cytoplasmic domain in Vpu-induced degradation in the endoplasmic reticulum. AB - The human immunodeficiency virus type 1 (HIV-1) Vpu protein is a transmembrane phosphoprotein which induces rapid degradation of CD4 in the endoplasmic reticulum (ER). To identify sequences in CD4 for Vpu-induced degradation, we generated four chimeric envelope glycoproteins having the ectodomain of HIV-1 gp160, the anchor domain of CD4, and 38, 25, 24, and 18 amino acids (aa) of the CD4 cytoplasmic domain. Using the vaccinia virus-T7 RNA polymerase expression system, we analyzed the expression of chimeric proteins in the presence and absence of Vpu. In singly transfected cells, the chimeric envelope glycoproteins having 38, 24, and 18 aa of the CD4 cytoplasmic domain were endoproteolytically cleaved and biologically active in the fusion of HeLa CD4+ cells. However, one of the chimeras having 25 aa of the CD4 cytoplasmic tail was retained in the ER using the transmembrane ER retention signal and was defective in membrane fusion. Furthermore, biochemical analyses of the coexpressing cells revealed that the Vpu protein induced degradation of the envelope glycoproteins having 38, 25, and 24 aa of the CD4 cytoplasmic tail and degradation occurred in the ER. Consequently, the fusion-competent glycoproteins did not induce the formation of syncytia in HeLa CD4+ cells expressing Vpu. However, the HIV-1 gp160 and chimeric envelope glycoprotein having the membrane-proximal 18 aa of the CD4 cytoplasmic tail were stable and fusion competent in cells expressing Vpu. In addition, we examined the stability of CD4 molecules in the presence of Vpu. Coexpression analyses revealed that the Vpu protein induced degradation of CD4 whereas mutant CD4 having the membrane-proximal 18 aa of the cytoplasmic domain was relatively stable in the presence of Vpu. Taken together, these studies have elucidated that the Vpu protein requires sequences or sequence determinants in the cytoplasmic domain of CD4 to induce degradation of the glycoproteins in the cell. PMID- 8350412 TI - Role of the His-Cys finger of Moloney murine leukemia virus integrase protein in integration and disintegration. AB - Retroviral integrases mediate site-specific endonuclease and transesterification reactions in the absence of exogenous energy. The basis for the sequence specificity in these integrase-viral DNA recognition processes is unknown. Structural analogs of the disintegration substrate were made to analyze the disintegration reaction mechanism for the Moloney murine leukemia virus (M-MuLV) integrase (IN). Modifications in the target DNA portion of the disintegration substrate decreased enzymatic activity, while substitution of the highly conserved CA in the viral long terminal repeat portion had no effect on activity. The role of the His-Cys finger region in catalysis was addressed by N ethylmaleimide (NEM) modification of the cysteine residues of M-MuLV IN as well as by mutations. Both integration activities, 3' processing, and strand transfer, were completely inhibited by NEM modification of M-MuLV IN, while disintegration activity was only partially sensitive. However, structural analogs of the disintegration substrates that were modified in the target DNA and had the conserved CA removed were not active with NEM-treated M-MuLV IN. In addition, mutants made in the His-Cys region of M-MuLV IN were examined and found to also be completely blocked in integration but not disintegration activity. These data suggest that the domains of M-MuLV IN that are required for the forward integration reaction substrate differ from those required for the reverse disintegration reaction substrate. PMID- 8350413 TI - A heptanucleotide sequence mediates ribosomal frameshifting in mammalian cells. AB - Ribosomal frameshifting is an essential requirement for replication of many viruses and retrovirus-like elements. It is regarded as a potential target for antiretroviral therapy. It has been shown that the frameshifting event takes place in the -1 direction within a sequence, the slippery sequence, which is usually followed by structured RNA. To distinguish between the basic sequence requirements and the modulating elements in intact cells, we have established a sensitive assay system for quantitative determination of ribosomal frameshifting in mammalian cell culture. In this assay system, the gag and pol genes of human immunodeficiency virus type 1 are replaced by the genes for the functional enzymes beta-galactosidase and luciferase, respectively. The sensitivity of the test system allows us to demonstrate for the first time that the slippery sequence, a heptanucleotide, is sufficient to mediate a basal level of ribosomal frameshifting independent of its position within a gene. The stem-loop sequence serves only as a positive modulator. These data indicate that frameshifting could also occur during translation of cellular genes in which a slippery sequence is present within the reading frame. The resulting putative transframe proteins might have a functional importance for cellular processes. PMID- 8350414 TI - Functional analysis of interactions between Tat and the trans-activation response element of human immunodeficiency virus type 1 in cells. AB - Transcriptional trans-activation of the human immunodeficiency virus type 1 long terminal repeat requires that the virally encoded Tat effector interacts with its target trans-activation response element (TAR) RNA stem-loop. Although the arginine-rich region of Tat from amino acids 49 to 59 is sufficient to bind to TAR RNA in vitro, the RNA-binding domain of Tat has not been defined in vivo. Human immunodeficiency virus type 1 also encodes the Rev protein, which acts through an RNA stem-loop called the Rev-response element to transport unspliced and singly spliced viral RNA species from the nucleus to the cytoplasm. To map the RNA-binding domain of Tat, we performed assays that relied on Rev function using the heterologous RNA-tethering mechanism of Tat and the TAR. By examining the effects of selected targeted mutations of Tat on the abilities of hybrid Tat/Rev proteins to rescue the expression of unspliced mRNA via the TAR, we demonstrated that residues throughout the N-terminal 59 amino acids of Tat are required for binding of Tat and TAR RNA in vivo. PMID- 8350416 TI - Evidence that the structural conformation of envelope gp120 affects human immunodeficiency virus type 1 infectivity, host range, and syncytium-forming ability. AB - We investigated how amino acid changes within and outside the V3 loop of the envelope glycoprotein of human immunodeficiency virus type 1 influence the infectivity, host range, and syncytium-forming ability of the virus. Our studies show that on the genomic backgrounds of the human immunodeficiency virus type 1 strains SF2 and SF13, a reciprocal exchange of full-loop sequences does not alter the syncytium-forming ability of the viruses, indicating that a determinant(s) for this biological property maps outside the loop. However, specific amino acid substitutions, both within and outside the V3 loop, resulted in loss of infectivity, host range, and syncytium-forming potential of the virus. Furthermore, it appears that a functional interaction of the V3 loop with regions in the C2 domain of envelope gp120 plays a role in determining these biological properties. Structural studies of mutant glycoproteins show that the mutations introduced affect the proper association of gp120 with the transmembrane glycoprotein gp41. Our results suggest that mutations that alter the structure of the V3 loop can affect the overall conformation of gp120 and that, reciprocally, the structure of the V3 loop is influenced by the conformation of other regions of gp120. Since the changes in the replicative potential, host range, and fusogenic ability of the mutant viruses correlate well with the changes in gp120 conformation, as monitored by the association of gp120 with gp41, our results support a close relationship between envelope gp120 structural conformation and the biological phenotype of the virus. PMID- 8350415 TI - V3 loop of the human immunodeficiency virus type 1 Env protein: interpreting sequence variability. AB - Two different states of human immunodeficiency virus type 1 are apparent in the asymptomatic and late stages of infection. Important determinants associated with these two states have been found within the V3 loop of the viral Env protein. In this study, two large data sets of published V3 sequences were analyzed to identify patterns of sequence variability that would correspond to these two states of the virus. We were especially interested in the pattern of basic amino acid substitutions, since the presence of basic amino acids in V3 has been shown to change virus tropism in cell culture. Four features of the sequence heterogeneity in V3 were observed: (i) approximately 70% of all nonconservative basic substitutions occur at four positions in V3, and V3 sequences with a basic substitution in at least one of these four positions contain approximately 95% of all nonconservative basic substitutions; (ii) substitution patterns within V3 are influenced by the identity of the amino acid at position 25; (iii) sequence polymorphisms account for a significant fraction of uncharged amino acid substitutions at several positions in V3, and sequence heterogeneity other than these polymorphisms is most significant at two positions near the tip of V3; and (iv) sequence heterogeneity in V3 (in addition to the basic amino acid substitutions) is approximately twofold greater in V3 sequences that contain basic amino acid substitutions. By using this sequence analysis, we were able to identify distinct groups of V3 sequences in infected patients that appear to correspond to these two virus states. The identification of these discrete sequence patterns in vivo demonstrates how the V3 sequence can be used as a genetic marker for studying the two states of human immunodeficiency virus type 1. PMID- 8350417 TI - Detection of Leishmania RNA virus 1 proteins. AB - Polyclonal antiserum was raised against the peak viral fraction of a sucrose gradient from LRV1-4-infected cells and used in Western immunoblot analysis to identify viral proteins from various isolates. Consistent with this result, in vitro-translated protein from cloned RNA was immunoprecipitated with the same antiserum. The putative capsid at times appeared as a doublet; relative amounts of the two species varied, depending on the method of purification. PMID- 8350418 TI - Evidence for a base-paired region of hepatitis B virus pregenome encapsidation signal which influences the patterns of precore mutations abolishing HBe protein expression. AB - In two natural HBe-minus hepatitis B virus mutants, expression of HBe protein was abrogated by a nonsense mutation at precore codon 28 and a frameshift mutation at codon 29, respectively. Both mutants contained an additional nucleotide substitution(s) which was found by transfection experiments to be required for efficient packaging of pregenomic RNA. The observed mutational profiles were consistent with the presence of a base-paired region of the pregenome encapsidation signal overlapping the HBe-coding sequence. Results obtained with artificial mutants with significant changes in the primary sequence suggested that base pairing is required but insufficient for efficient pregenome packaging. However, the predicted first four base pairs of the stem are dispensable. PMID- 8350419 TI - The major capsid protein VP2 of minute virus of mice (MVM) can form particles which bind to the 3'-terminal hairpin of MVM replicative-form DNA and package single-stranded viral progeny DNA. AB - The capsids of minute virus of mice (MVM) consist of two closely related proteins, VP1 and VP2. We inactivated the VP1 gene in an infectious clone of MVM DNA by frameshift mutation. After transfection of mutated DNA, capsids consisting of VP2 only were made. They can package negative-strand DNA, and they specifically bind MVM 3'-terminal hairpin DNA. PMID- 8350420 TI - Bovine herpesvirus 1: immune responses in mice and cattle injected with plasmid DNA. AB - Mice and cattle injected with plasmids encoding bovine herpesvirus 1 (BHV-1) glycoproteins developed gene-specific antibody responses capable of neutralizing BHV-1. The ability of animals to respond serologically to DNA injections was in part dependent on the quantity of DNA injected and was also negatively affected by carrier DNA. Calves injected with a plasmid encoding BHV-1 gIV developed significant antibody titers to gIV and shed less virus than did the control calf after challenge. This report indicates the potential of DNA injection as a method of vaccination. PMID- 8350421 TI - The small subunit of the vaccinia virus early transcription factor contacts the transcription promoter DNA. AB - The vaccinia virus early transcription factor (VETF), in addition to the viral RNA polymerase, is required for efficient transcription of early genes in vitro. VETF is a heterodimeric protein that binds specifically to early gene promoters. In order to localize the VETF DNA binding domain, we have used photoreactive oligonucleotide probes with the sequence of the vaccinia virus growth factor promoter. The probes consisted of double-stranded oligonucleotides incorporating radiolabeled dAMP and 5-bromo-dUMP into sequences of the promoter known to contact VETF. Irradiation of a DNA probe having these nucleotides located upstream of the transcription start site in the presence of VETF resulted in the transfer of label to a polypeptide that comigrated with the small subunit of VETF. The label transfer reaction was shown to occur with the recombinant VETF small subunit in the absence of the large subunit. These results indicate that the small subunit comprises at least part of the VETF DNA binding domain and contacts the promoter in the region upstream of the transcription start site. PMID- 8350423 TI - Regional adenosine attenuates postischemic spinal cord injury. AB - PURPOSE: Operations on the thoracic and thoracoabdominal aorta are associated with postoperative paraplegia rates as high as 20% to 30%. Attempts to reduce this complication have focused on decreasing the energy needs of the spinal cord with protective agents such as hypothermia and barbiturates or on increasing blood flow with various shunts. This study explores the hypothesis that perfusion of the spinal cord with hypothermic solutions or with adenosine will prevent or ameliorate paraplegia. METHODS: New Zealand white rabbits underwent 40 minutes of infrarenal aortic isolation. The infrarenal aorta is the primary source of spinal cord blood supply in the New Zealand white rabbit. Control rabbits sustained aortic occlusion without any protective measures. The remaining animals were randomized into three groups that underwent aortic cross-clamping with various protective adjuncts. Group I received regional aortic hypothermia perfusion, group II received systemic adenosine, and group III received regional aortic perfusion with high-dose adenosine. RESULTS: Neurologic function was graded according to the Tarlov scale (0 = no movement, 1 = slight movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop). After 96 hours animals were euthanized, and spinal cords were harvested for histologic examination. The nonparaplegic animals in group I had a mean Tarlov score of 1.5, whereas those in group III had a mean score of 3.4. Histologic studies on spinal cord tissue revealed no significant differences between the study groups. CONCLUSIONS: These data demonstrate that administration of regional adenosine attenuates ischemic injury associated with aortic occlusion in this experimental model. PMID- 8350422 TI - Transcomplementation of simian immunodeficiency virus Rev with human T-cell leukemia virus type I Rex. AB - A molecular clone of the simian immunodeficiency virus SIVSMM isolate PBj14, lacking the ATG initiation codon for Rev protein (PBj-1.5), did not produce virus or large unspliced or singly spliced viral RNA upon transfection of HeLa cells. Low but significant levels of virus and large viral RNA production were observed upon transfection of PBj-1.5 into HeLa Rev cells expressing the rev gene of human immunodeficiency virus type 1. Furthermore, abundant virus and large viral RNA production occurred upon transfection of PBj-1.5 into HeLa Rex cells expressing the rex gene of human T-cell leukemia virus type I. Virus produced from HeLa Rex and HeLa Rev transfections was infectious, produced large amounts of virus, and was cytopathic for Rex-producing MT-4 cells. In contrast, no or only low levels of virus production were observed upon infection of H9 cells. These studies show that a defective SIV rev gene can be transcomplemented with human immunodeficiency virus type 1 Rev and with high efficiency by human T-cell leukemia virus type I Rex, and they suggest that rev-defective viruses could serve as a source for production of a live attenuated SIV vaccine. PMID- 8350424 TI - Cigarette smoke alters chylomicron metabolism in rats. AB - PURPOSE: Cigarette smoking may exert its atherogenic effect by delaying the plasma clearance of dietary fat and cholesterol, allowing more time for their interaction with the artery wall. To study the effects of smoke on chylomicron metabolism in rats, we examined the metabolic effects of smoke on both whole animals and chylomicron particles in vitro. METHODS: Carbon 14- and hydrogen 3 labeled chylomicrons were injected intravenously into smoke-treated rats and control rats that were not exposed to smoke (sham smoked). Plasma clearance, hepatic uptake, and heart binding were measured. In a second set of experiments, chylomicron particles were exposed to cigarette smoke in vitro by either: (1) passing smoke through chylomicrons suspended in saline solution (SCM) or (2) passing smoke through saline solution alone, then mixing the saline solution with chylomicrons (CM + SS). Normal (non-smoke exposed) rats were infused with either SCM, CM + SS, or control chylomicrons (CCM). Plasma clearance, hepatic uptake, and heart binding were again measured. RESULTS: The initial plasma clearance time of labeled chylomicrons did not differ between smoke-treated and control animals. However, hepatic uptake of chylomicron cholesterol was slower in smoke-treated animals (46.1% +/- 0.9% of injected dose) than in controls (61.5% +/- 2.1%, p < 0.001). In contrast, more labeled chylomicrons remained in the heart of smoke treated rats than controls (0.89% +/- 0.18% vs 0.45% +/- 0.05%, p < 0.05). Disappearance of 14C-labeled cholesterol from blood was delayed in rats injected with SCM (half-life = 9.0 +/- 0.4 minutes) and CM + SS (half-life = 8.0 +/- 0.4 minutes), compared with the time in rats injected with CCM (6.6 +/- 0.3 minutes, p < 0.05). Hepatic uptake of SCM (40.6% +/- 1.9% of injected dose) and CM + SS (45.0% +/- 1.9%) was less than that of CCM (60.7% +/- 4.4%, p < 0.05). In addition, the binding to the heart increased from 0.97% +/- 0.29% (CCM) to 2.45% +/- 0.30% with the infusion of SCM (p < 0.05). The binding in the heart of CM + SS (0.95% +/- 0.04%) was not different from that of CCM. CONCLUSIONS: These data demonstrate for the first time that cigarette smoke exposure prolongs chylomicron residence time in tissues (heart) and delays hepatic uptake of chylomicron cholesterol in rats. The effect is present when either the animal or the chylomicron particle is exposed to smoke. We hypothesize that prolonged binding of relatively cholesterol-rich chylomicron remnants to endothelial surfaces could create a more atherogenic postprandial milieu. PMID- 8350425 TI - Distribution of c-myc oncoprotein in healthy and atherosclerotic human carotid arteries. AB - PURPOSE: Smooth muscle cell (SMC) proliferation is a central event in the development of arteriosclerotic plaque. Regulation of this proliferative process is controlled in part by the action of specific peptide growth factors that may influence early cell-cycle regulatory gene expression. Such "early" response genes include the protooncogene c-myc, which has been implicated in the induction of cell proliferation and differentiation. We compared the distribution of the c myc protooncogene product in healthy and atherosclerotic human carotid arteries to determine its cellular and tissue localization. METHODS: Samples of six carotid artery plaques from six patients were rapidly frozen in liquid nitrogen at the time of carotid endarterectomy. Three nondiseased human carotid arteries obtained at organ harvest from brain-dead organ donors were similarly prepared. Frozen sections were labeled with a polyclonal rabbit anti-c-myc antibody that recognizes the 64 kd c-myc human protein. The percentages of cells positive for c myc (c-myc index) and the intensity of antibody labeling were determined. RESULTS: Normal human carotid artery demonstrated minimal, isolated cell staining, with single scattered grains of immunocytochemical staining product seen in SMC nuclei. The myc index was 14.7% +/- 3.5% positive cells. In comparison, SMCs from carotid plaque showed a significant predominance of c-myc immunoreactive cells (89.8% +/- 4%; p < 0.001). The intensity of c-myc staining was greater in plaque SMCs, with many of the cells demonstrating confluence of immunocytochemical precipitate throughout 50% of SMC nuclei. CONCLUSIONS: Although the exact role of enhanced expression of the c-myc protooncogene in atherosclerosis is unclear, a cooperative influence of abnormal early cell-cycle gene expression and humoral factors may initiate the atherogenic process. The c myc gene and other protooncogenes are early molecular markers of cell-cycle activity, which may be important in the development of atherosclerosis and occlusive vascular disease. PMID- 8350426 TI - Endothelin production by hypoxic human endothelium. AB - PURPOSE: The physiologic significance of endothelin remains incompletely defined. Procoagulant and antifibrinolytic activities are increased in hypoxic cultured human umbilical venous endothelial cells (HUVEC). We examined the effect of hypoxia on HUVEC endothelin-1 production in vitro to determine whether a correlation existed between the procoagulant and antifibrinolytic response to hypoxia previously observed and an increase in vasoconstrictor peptide secretion by hypoxic HUVEC. METHODS: Cultured HUVEC were rendered hypoxic (PO2 = 40 mm Hg) or control (PO2 = 120 mm Hg) for 24 hours. Media were either standard, 5 gm glucose/L (high glucose), or contained 500 units superoxide dismutase/ml (SOD). Endothelin-like immunoreactivity for endothelin-1 (ET-IR) in conditioned media was measured by radioimmunoassay and expressed as mean femtomoles per milliliter (+/- SD) per 100,000 cells. Viability of HUVEC was assessed by trypan blue exclusion. Significance was determined by use of Student's t test. RESULTS: Conditioned media from hypoxic cells contained 76% more ET-IR than was found in control counterparts (p < 0.004). The addition of high glucose or SOD did not diminish ET-IR; a trend to higher ET-IR was present in both these groups versus standard media (303% and 226%, respectively, p < 0.03). CONCLUSIONS: Thus 24 hours of hypoxia caused an increase in conditioned-media ET-IR in cultured HUVEC. Because SOD or greater substrate availability did not diminish endothelin presence in conditioned media, it seems that hypoxic induction of endothelin-1 production or secretion is signaled in a fashion unrelated to cell toxicity from the hypoxic period. PMID- 8350427 TI - Transfemoral endovascular aortic graft placement. AB - PURPOSE: The purpose of this study was to develop an endovascular system for transfemoral placement of straight aortic grafts and bifurcated aortoiliac grafts. METHODS: Both types of graft consist of barbed, self-expanding stents attached to a woven polyester fabric. Survival studies of straight-graft function were performed in six large mongrel dogs. Digital subtraction fluoroscopic equipment was used to guide insertion and record angiograms at 0, 1, and 3 months. Bifurcated grafts were inserted in an additional eight dogs, four with distal stents and four without. Straight grafts were inserted into six cadaveric aortas (five atherosclerotic and one aneurysmal; age 68.7 + 5.7 years) to assess stent attachment. RESULTS: Angiograms obtained immediately after straight-graft insertion showed placement to be within 4.6 + 1.6 mm of the intended level. Follow-up angiograms at 1 and 3 months showed no migration, no leakage, and patency of all six grafts. After bifurcated graft insertion there were no angiographic signs of perigraft leakage, with or without distal stents. The mean force required to displace straight grafts 10 mm from their original position in cadaveric aortas was 1388 + 127 g. CONCLUSION: These preliminary results show that straight and bifurcated endovascular grafts can be positioned accurately and securely in the abdominal aorta. PMID- 8350428 TI - Saphenous vein angioscopy: a valuable method to detect unsuspected venous disease. AB - PURPOSE: The presence of preexisting saphenous vein lesions adversely affects graft patency. Despite careful preoperative venous duplex examination and meticulous intraoperative evaluation, clinically significant saphenous vein disease may remain undetected. We evaluated angioscopy as a means to better detect these vein lesions. METHODS: Ninety saphenous vein remnants, obtained at bypass surgery, were perfusion fixed for subsequent angioscopic and histologic evaluation. The specimens were categorized by independent examiners on the basis of the angioscopic or light microscopic findings. Of the 90 vein remnants, 66 were normal by angioscopic criteria. Fifty-three (80%) of these angioscopically normal vein segments were normal histologically, and all 24 angioscopically abnormal saphenous vein remnants showed disease on microscopic examination. RESULTS: Angioscopy correctly identified sclerotic vein segments (n = 20) by irregular white plaques, whereas postphlebitic veins (n = 3) demonstrated multiple lumens, fibrous strands, and thickened opaque valve cusps on angioscopic evaluation. Absence of an angioscopic lumen was confirmed histologically in occluded veins (n = 2). Angioscopy failed to identify thick-walled (n = 10) and varicose (n = 2) vein segments as abnormal; one sclerotic segment was normal angioscopically, thereby lowering the sensitivity of angioscopy. CONCLUSIONS: Angioscopy detected unsuspected preexisting saphenous vein disease in five patients undergoing arterial reconstruction with saphenous vein. Because the use of angioscopy is a reliable means of prospectively assessing the vein for most preexisting lesions, its routine use may ultimately improve graft patency. PMID- 8350429 TI - Periodic hemodynamics (flow motion) in peripheral arterial occlusive disease. AB - PURPOSE: The occurrence of periodic blood flow variations (flow motion) in health and disease is controversially discussed. This is partly due to not reporting the incidence and to performing the analysis solely visually. We have therefore studied flow motion with computerized methods. METHODS: We used a computerized Prony spectral line estimator program to analyze the frequencies of resting skin blood flow variations, as determined by laser Doppler flowmetry on the thumb and great toe, in 50 male control subjects (group a), in 50 patients with mild peripheral arterial occlusive disease (PAOD stages I and II; group b), and in 25 patients with severe PAOD (stages III and IV; group c). RESULTS: The median ankle/arm pressure ratio was 1.10 in the control group, 0.72 in the mild PAOD group, and 0.66 in the severe PAOD group. Slow wave flow motion was detected in 19% of all thumbs from groups a and b (systolic arm pressures > 100 mm Hg) and in 12% of the toes in the control group. Patients with mild PAOD exhibited slow wave flow motion in 46% of the toes. Patients with severe PAOD showed slow waves in 77% of the toes. The median flow motion frequencies were about 1.6 cycles/min for groups a and b, when present. The median frequency in group c was significantly higher at 4.0 cycles/min, though still in the range of slow waves. The median peak-to-through amplitude was between 17% and 20% of mean flow for all groups. CONCLUSIONS: We conclude that evaluation of flow motion requires computerized frequency analysis and that slow wave flow motion is a perfusion pattern characteristic of PAOD rather than of normal perfusion states. This finding has potential implications for diagnostic and therapeutic approaches in arterial occlusive disease. PMID- 8350430 TI - Cryopreserved venous allografts: effects of immunosuppression and antiplatelet therapy on patency and function. AB - PURPOSE: Experiments were designed to determine the function of the endothelium and smooth muscle in cryopreserved and fresh canine saphenous vein allografts. METHODS: Reversed interposition saphenous vein grafts were implanted into the femoral arteries of two groups of dogs: group 1 received one freshly harvested saphenous vein allograft and group 2 received one cryopreserved saphenous vein allograft. The contralateral femoral artery in each group was replaced with a freshly harvested autogenous saphenous vein. Animals received oral cyclosporine alone (n = 3) or in combination with aspirin (325 mg/day; n = 20). RESULTS: Four weeks after surgery, none of the cryopreserved grafts was patent in the group treated with cyclosporine alone. All grafts were patent in animals treated with cyclosporine and aspirin. At 4 weeks, blood flow through cryopreserved allografts was significantly greater than in freshly harvested allografts. Platelet deposition was comparable in cryopreserved and freshly harvested allografts immediately after implantation and at 4 weeks. Rings cut from the grafts were suspended for the measurement of isometric force in organ chambers. alpha Adrenergic agonists and endothelin caused concentration-dependent contractions in fresh autografts and allografts. After submaximal contraction with prostaglandin F2 alpha in these same grafts, calcium ionophore and thrombin caused relaxations in rings with endothelium, and nitric oxide caused relaxations in rings without endothelium. Cryopreserved allografts did not respond to any of the agonists tested. Histologic examination of the tissue indicated smooth muscle cells in cryopreserved grafts; evidence of rejection was observed in all allografts. CONCLUSION: These results indicate that cryopreserved allografts remain patent with antiplatelet and immunosuppressive therapy in spite of loss of functional smooth muscle. PMID- 8350431 TI - Alloxan diabetes alters the rabbit transarterial wall oxygen gradient. AB - PURPOSE: Atherosclerotic vascular occlusive disease is the most common complication of diabetes mellitus and accounts for 75% of deaths in diabetic patients. Determining the initiator and continuing stimulus for the cellular events in the formation of atherosclerotic lesions in diabetic patients could lead to the prevention of this common and deadly complication. Diabetes-induced arterial wall hypoxia is proposed as an initiator and continuing stimulus for atherosclerotic vascular occlusive disease. METHODS: Transarterial wall oxygen gradient measurements were performed on the infrarenal aorta with an oxygen microelectrode 14 to 16 weeks after the induction of alloxan diabetes in rabbits. RESULTS: Both insulin-treated and untreated alloxan diabetic rabbits revealed significantly decreased oxygen tensions throughout the arterial wall compared with control rabbits. There was no significant difference in the transarterial wall oxygen gradient between the two groups of diabetic rabbits. This effect was noted despite no difference in the partial pressure of oxygen in arterial blood or visual evidence of atherosclerotic lesion formation in the three groups. CONCLUSIONS: These findings suggest that diabetes induces arterial wall hypoxia independent of insulin therapy and before the formation of atherosclerotic lesions. Diabetes-induced arterial wall hypoxia may contribute to the formation of atherosclerotic lesions. PMID- 8350433 TI - Persistent sciatic artery: embryology, pathology, and treatment. AB - PURPOSE: The purpose of this article is to describe the embryologic development and anomalous persistence of the sciatic artery, pathologic changes that may occur in the persistent sciatic artery, and management of complications related to these pathologic changes. METHODS: Two patients with persistence of the sciatic artery treated in the authors' experience are reported. In addition, the computerized data base of the University of Mississippi Medical Center was searched for patients with other lower extremity arterial aneurysms, and their records were reviewed for possible aneurysm of a persistent sciatic artery. A review of the literature was undertaken to determine the embryologic development of the persistent sciatic artery, the pathologic changes that have been observed in the sciatic artery, clinical findings associated with these pathologic changes, and methods of treatment. RESULTS: Two patients with persistence of the sciatic artery were treated by the authors. No other cases were identified in 43 patients with 66 lower extremity aneurysms treated at our institution. The first patient presented with acute lower extremity ischemia caused by thrombosis of a sciatic artery aneurysm and was treated successfully with intraarterial thrombolytic therapy followed by interposition graft repair. In the second case an incidental unilateral persistent sciatic artery was identified in a patient with bilateral Buerger's disease presenting with digital gangrene of the contralateral extremity in whom below-knee amputation was eventually required. Bilateral tibial artery occlusion was observed on arteriography. Histologic examination of the amputated limb confirmed findings typical of Buerger's disease, and no microemboli were seen. DISCUSSION: The sciatic artery is a continuation of the internal iliac artery and is the primary blood supply to the lower limb bud during early fetal development. The sciatic artery normally involutes during fetal development, but remnants persist as the popliteal and peroneal arteries after the superficial femoral artery develops and establishes continuity with the popliteal artery. Persistence of the sciatic artery as the major blood supply to the lower extremity in adults is a rare vascular anomaly that may be of surgical significance. Failure to appreciate the persistent sciatic artery as the major inflow into the lower extremity may lead to inappropriate bypass of apparent occlusive disease of the superficial femoral artery. The persistent sciatic artery is also frequently aneurysmal, which may cause critical limb ischemia resulting from thrombosis or embolization of aneurysm thrombus. Options for vascular reconstruction include interposition graft replacement and standard femoropopliteal bypass grafting if the common femoral artery is sufficiently developed to provide adequate inflow. As with other peripheral arterial aneurysms resulting in thrombosis and extensive distal arterial embolization and thrombosis, intraarterial thrombolytic therapy may be useful in selected cases before definitive surgical revascularization. PMID- 8350432 TI - The preferential use of the external iliac artery as an inflow source for redo femoropopliteal and infrapopliteal bypass. AB - PURPOSE: It is believed that secondary operations involving the inguinal region are associated with a significant morbidity that includes infection, lymphatic obstruction, lymphorrhea, and neurovascular injury. To prevent these potentially important complications we have avoided a redo groin incision in 38 patients with severely symptomatic disease who had primary (23 cases) or secondary (15 cases) femoropopliteal bypass thrombosis during the past 3 years. METHODS: All patients were candidates for prosthetic bypasses because of lack of a suitable vein. Twenty-nine external iliac-to-popliteal bypasses (18 above-knee; 11 below-knee) and nine external iliac-to-infrapopliteal bypasses (five anterior tibial; two posterior tibial; two peroneal) were performed with 6 mm polytetrafluoroethylene ringed grafts in 38 patients. Adjunctive distal arteriovenous fistulas were constructed in all infrapopliteal bypasses. The external iliac artery was exposed via a retroperitoneal approach. The second incision was placed just below the scarred area and deepened to the level of the medial border of the sartorius muscle. A tunnel that connected both incisions was easily created by blunt dissection alongside the anterolateral border of the femoral artery. RESULTS: Four popliteal bypasses occluded at 4, 6, 10, and 28 months after operation. The remaining 25 grafts are patent (mean 14 months). Three of the infrapopliteal bypasses occluded at 0, 2, and 3 months after operation. The remaining six grafts are patent with follow-up from 4 to 18 months (mean 12 months). Only one patient had a superficial wound infection at the below-knee popliteal incision, which healed with local treatment. All other patients had an uneventful postoperative course. CONCLUSIONS: Thus we believe this approach to be simple, safe, and durable and should be used preferentially to avoid the difficult and hazardous dissection of a previously operated groin. PMID- 8350434 TI - Late nonfatal and fatal cardiac events after infrainguinal bypass for femoropopliteal occlusive disease during a thirty-one-year period. AB - PURPOSE AND METHODS: In patients with peripheral vascular disease the complications of associated coronary artery disease have always been a leading cause of morbidity and mortality. Therefore we evaluated the risk for late cardiac morbidity and mortality in 376 consecutive patients after infrainguinal bypass. Follow-up was complete for 373 patients (99.3%) with a mean follow-up period of 5.9 years. After operation all but four patients were treated with lifelong warfarin (Coumadin therapy.) RESULTS: During follow-up 129 patients (34.3%) had 183 late cardiac events. Of these patients, 79 (61.2%) died of late cardiac events and 13 (10.0%) required either coronary angioplasty or bypass. The risk of late cardiac events was 34% at 5 years and increased to 56% at 15 years. Multivariate analysis demonstrated that age, cardiac disease, and impaired renal function at the time of operation were associated with an increased risk of cardiac events during follow-up. Independent predictors of cardiac death were age, cardiac disease, hypertension, diabetes, and impaired renal function. Morbidity and mortality was particularly high in patients with critical ischemia. The subset of patients with claudication had a life expectancy that appeared to be similar to that of a matched sample of the normal population. CONCLUSIONS: Our findings clearly demonstrate that some patients undergoing infrainguinal bypass are at high risk for late cardiac events of which many are fatal, whereas others may have an almost normal life expectancy. Most important, the occurrence of cardiac events may be predicted by simple and readily obtainable clinical variables at the time of the initial infrainguinal bypass procedure. Because these events were related to late cardiac death, this may be the key for angiographic evaluation and possible prevention of cardiac death. PMID- 8350435 TI - Should the Cell Saver Autotransfusion Device be used routinely in all infrarenal abdominal aortic bypass operations? AB - PURPOSE: The purpose of this study was to attempt to identify a group of patients undergoing infrarenal aortic bypass in whom blood loss is consistently less than 2 units, making the routine use of autotransfusion devices unnecessary. METHODS: Four groups of patients were prospectively studied as follows: abdominal aortic aneurysm (AAA) repair with tube graft (n = 21), AAA repair with bifemoral or biiliac bypass (n = 19), and aortobifemoral bypass (AFB) or biiliac bypass for occlusive disease either with Cell Saver Autotransfusion Device (Haemonetics Corp., Braintree, Mass.) (n = 18) or without Cell Saver (n = 18). The latter two groups were randomized on an alternating basis. RESULTS: The following parameters were obtained on all patients: preoperative hemoglobin values, estimated blood loss, Cell Saver return volumes, intraoperative and postoperative homologous blood transfused, postoperative hemoglobin values on the day of surgery and on postoperative days 1 and 4, complications, and length of hospital stay. In comparing the groups undergoing AFB with Cell Saver and AFB without Cell Saver by the above parameters, we found no statistically significant differences, except for a higher hemoglobin level on postoperative day 1 in the group undergoing AFB with Cell Saver (mean 11.86 vs 10.74, p = 0.02). The estimated blood loss and Cell Saver return volumes were less for those patients undergoing AFB for occlusive disease compared with those undergoing AFB for aneurysmal disease. Interestingly, estimated blood loss and Cell Saver return volumes for patients with AAA with tube graft and patients undergoing AFB with Cell Saver were similar. CONCLUSIONS: We conclude that routine setup and use of rapid autotransfusion devices may not be necessary in every patient undergoing routine aortofemoral bypass for occlusive disease. Furthermore, the possibility that some patients may undergo AAA repair with tube grafts without use of the Cell Saver may be deserving of further investigation. PMID- 8350436 TI - Expression and sequence of the gene for tissue inhibitor of metalloproteinases in patients with abdominal aortic aneurysms. AB - PURPOSE: The tissue inhibitors of metalloproteinases (TIMPs) are major inhibitors of several enzymes that are destructive to connective tissue, and TIMP-1 has been reported to be deficient in the wall of abdominal aortic aneurysms. This deficiency could represent failure of expression resulting from either local tissue conditions or mutation in the primary structure of the gene (or one of its regulatory elements). METHODS: Southern blotting techniques were used to examine the possibility of global deletions or inserts in the gene (14 patients); Northern blot techniques were performed to examine the expression of the mRNAs in cultured fibroblasts under basal conditions (six patients); and sequence analysis of the cDNA derived from fibroblast mRNAs was done after amplification by polymerase chain reaction (six patients). RESULTS: The Southern blots revealed a normal distribution of the known alleles of the gene without unique restriction length polymorphisms. Fibroblast expression of TIMP mRNA was normal under basal conditions. Sequence analysis of the cDNAs revealed an identical-point polymorphism in two of the six patients (a single base pair substitution of C-->T at the third position in codon 101), but the amino acid was conserved. CONCLUSION: The studies reported here do not support the hypothesis that deficiency of TIMP-1 in specimens of aorta of patients with abdominal aortic aneurysms results from a primary genetic defect. PMID- 8350437 TI - Long-term results of semiclosed endarterectomy of the superficial femoral artery and the outcome of failed reconstructions. AB - PURPOSE: The optimal method of treatment of superficial femoral artery occlusive disease has yet to be established. Therapeutic options include percutaneous transluminal angioplasty for short lesions and reversed or in situ autologous saphenous vein bypass for long lesions. Currently, staged revascularization with polytetrafluoroethylene as an initial conduit and autologous vein for secondary procedures is suggested. An alternative to these procedures is endarterectomy of the occluded superficial femoral artery, followed by a femoropopliteal bypass in cases of endarterectomy failure. Our results with this procedure are reviewed in this article. METHODS: From 1980 until 1990, 259 endarterectomies of the superficial femoral artery were attempted, 231 of which were successfully performed in 197 patients (145 men and 52 women), with an average age of 64 years (range 40 to 82 years). The indication for successfully performed endarterectomy was claudication in 186 patients (80%), rest pain in 21 (9%), and gangrene in 24 (11%). The postoperative mortality rate was 0.8% with a complication rate of 10%. RESULTS: Eighty-two failures occurred during follow-up, of which 33 were treated with peripheral bypass. Five additional bypasses were performed because of occlusions distal from the endarterectomized segment. The 5-year primary overall patency rate of successfully performed endarterectomy was 71% (SE 3.6). The 5 year overall secondary bypass patency rate was 61% (SE 11.3). The combined endarterectomy and bypass patency rate (tertiary patency) was 79% (SE 3.3) after 5 years and 45% (SE 7.6) after 10 years. The overall amputation rate was 5.6% and the amputation rate was 1.6% in patients treated for claudication. CONCLUSIONS: The combination of endarterectomy and peripheral bypass provides a valuable alternative to the current treatment of superficial femoral artery occlusive disease. PMID- 8350438 TI - Practice guidelines: lower extremity revascularization. PMID- 8350439 TI - Percutaneous transfemoral insertion of a stented graft to repair a traumatic femoral arteriovenous fistula. AB - This case report describes a new approach to repair a femoral arteriovenous fistula with a transluminally placed intraarterial graft-covered stent. A balloon expandable stented polytetrafluoroethylene graft was inserted percutaneously to obliterate an arteriovenous fistula after a bullet injured the left superficial femoral artery and vein of an 18-year-old man. Follow-up duplex ultrasonography at 5 months demonstrated patency and luminal integrity of the involved artery and vein, with resolution of the associated pseudoaneurysm. Additional follow-up will be needed to further substantiate the utility of this minimally invasive procedure in the treatment of traumatic arterial injuries. PMID- 8350440 TI - Penetration of the wall of an abdominal aortic aneurysm by a Greenfield filter prong: a late complication. AB - This is a case report of a 68-year-old woman in whom a late and previously unreported complication developed that resulted from penetration of an aortic aneurysm by the prong of a stainless steel Greenfield filter. This complication came into view 7 years after placement of the filter, at the time of aneurysm resection. Enlargement of the aneurysm had occurred at a rapid rate. The patient was symptom free before surgery. PMID- 8350441 TI - Abdominal aortic pseudoaneurysm after blunt trauma. AB - A 4-year-old male child was admitted with a large 12 x 15 cm suprarenal abdominal aortic pseudoaneurysm 7 months after an episode of blunt abdominal trauma. Aneurysmorrhaphy was performed through a left thoracoabdominal approach with Dacron patch aortoplasty. This report summarizes this case and reviews the literature on abdominal aortic pseudoaneurysms after blunt abdominal trauma. PMID- 8350442 TI - Aorta-left renal vein fistula syndrome caused by rupture of a juxtarenal abdominal aortic aneurysm: novel pathologic mechanism for a unique clinical entity. AB - Spontaneous aorta-left renal vein fistula (ALRVF) caused by abdominal aortic aneurysm (AAA) is a rare form of intravascular aneurysm rupture. The literature series of ALRVF, updated here to 19 reported cases, demonstrates that patients with ALRVF present with a unique clinical syndrome characterized by abdominal or left flank pain (84%), a pulsatile abdominal mass (63%), abdominal bruit or murmur (63%), hematuria (100%), and nonfunction of the left kidney on functional imaging studies (100% of patients studied). Operative findings in ALRVF syndrome have included a large AAA (mean diameter 9.2 cm), with frank rupture in only three; in 17 of 19 patients (89%) the ALRVF was associated with a retroaortic left renal vein anomaly. The patient presented here had a large juxtarenal AAA with rupture into the left retroperitoneal space. The wide aneurysm neck and expanding hematoma created an avulsion of the second left lumbar vein from its junction with an anatomically normal (preaortic) left renal vein; the resulting renal vein tear allowed development of an arteriovenous communication that was responsible for the clinical presentation of ALRVF syndrome. The disease found here demonstrates a novel mechanism for the production of ALRVF syndrome in patients with juxtarenal AAA and otherwise normal pararenal venous anatomy. PMID- 8350443 TI - A piece of my mind. Primary caring. PMID- 8350444 TI - Preparedness for practice. Young physicians' views of their professional education. AB - OBJECTIVE: To describe the views of young physicians (younger than age 45 years) regarding the appropriateness of specific aspects of medical training that have often been criticized as inadequate. DESIGN: Proportional analysis of survey data, stratified by medical school type and graduate medical education specialty and adjusted for demographics. SETTING: National sample of 4756 allopathic and osteopathic physicians trained in allopathic residencies representing a variety of practice settings. DEPENDENT VARIABLES: Overall satisfaction with medical training, including medical school through residency and fellowship; satisfaction with preparedness for five aspects of practice and six types of patients; and satisfaction with the amount of time spent in each of six training settings. RESULTS: Eighty percent of young physicians reported that their formal medical training did an excellent or good job of preparing them for medical practice. Much smaller proportions (21% to 78%) reported excellent or good preparation to treat specific conditions or types of patients, and few (3%) reported being well prepared to manage business aspects of practice. Large proportions (35% to 63%) would prefer to have received more training in settings outside of hospitals, including managed care settings (67%). Significant differences in preparedness were observed by type of training; those trained in general and family practice reported better preparedness along many dimensions than did those trained in general internal medicine. CONCLUSIONS: Young physicians generally confirm critiques of medical training noted by scholars and commissions. Health care reform is likely to increase the urgency for remedial action. PMID- 8350445 TI - ECFMG assessment of clinical competence of graduates of foreign medical schools. Educational Commission for Foreign Medical Graduates. AB - OBJECTIVE: To develop an assessment of clinical competence of graduates of foreign medical schools and to determine the reliability and validity of the assessment and the feasibility of large-scale administration. DESIGN: The Educational Commission for Foreign Medical Graduates (ECFMG) clinical competence study included (1) clinical encounters with standardized patients to assess history taking, physical examination, and communication skills; (2) laser videodisk pictorials to assess identification and interpretation of diagnostic procedures; (3) written clinical vignettes to assess diagnosis and management skills; and (4) assessment of spoken English. A uniform method of operating the test centers and of training the standardized patients was developed. SETTING: Medical schools and their primary teaching hospitals and affiliated hospitals. PARTICIPANTS: Six hundred twenty-four first-year residents, of whom 525 are graduates of foreign medical schools. MAIN OUTCOME MEASURES: Scores, reliability coefficients, validity measures, feasibility of multisite administration, trends of scores over time, and acceptability by examinees. RESULTS: The ECFMG clinical competence assessment was conducted at four geographically separate test centers. Reliability coefficients were high (.85) for the integrated clinical encounter and were in a reasonable range (.71 to .82) for all test components. The assessment adds to the predictability of the residents' performance in the hospital over that of current ECFMG certification examinations. Test security was addressed by demonstrating no consistent pattern of change in scores over testing dates. Virtually all examinees thought the assessment was appropriate. Standardized patients were able to assess spoken English accurately. CONCLUSION: The feasibility of conducting a reliable and valid test of clinical competence for graduates of foreign medical schools was demonstrated for this test population. PMID- 8350446 TI - Competency assessment of primary care physicians as part of a peer review program. AB - OBJECTIVE: To design and test a program that assesses clinical competence as a second stage in a peer review process and to determine the program's reliability. DESIGN AND SETTING: A three-cohort study of Ontario primary care physicians. PARTICIPANTS: Reference physicians (n = 26) randomly drawn from the Hamilton, Ontario, area; volunteer, self-referred physicians (n = 20); and physicians referred by the licensing body (n = 37) as a result of a disciplinary hearing or peer review. MAIN OUTCOME MEASURES: Standardized patients, structured oral examinations, chart-stimulated recall, objective structured clinical examination, and multiple-choice examination. RESULTS: Test reliability was high, ranging from 0.73 to 0.91, and all tests discriminated among subgroups. Demographic variables relating to the final category were age, Canadian or foreign graduates, and whether or not participants were certified in family medicine. CONCLUSIONS: The study demonstrated the feasibility, reliability, and validity of a multicomponent examination in the peer review process. PMID- 8350447 TI - Institutional responsibility in graduate medical education and highlights of historical data. PMID- 8350448 TI - Educational programs in US medical schools. AB - As described in the introduction, the data presented in this report can be viewed in both a historical and an environmental context. From a historical perspective, there has been change in many areas of medical education. The number of applicants to medical schools has risen sharply in the past few years, a result seemingly inconsistent with the dissatisfaction with medicine expressed by many physicians and with the uncertainties about the eventual outcomes of health system reform. The number of minority applicants and enrollees is slowly rising, but at rates below the goals identified by such initiatives as the Association of American Medical Colleges' "Project 3000 by 2000." Even with the expansion of the applicant pool, however, most medical schools do not anticipate enrollment increases. Medical school tuition also continues to increase significantly, in both public and private schools. The number of faculty members in the clinical disciplines also has continued to rise, although the rate of increase has become less marked. The decrease in the number of basic science faculty members that occurred this year will need to be monitored to ensure that appropriate faculty resources are available for teaching, especially with the initiatives to introduce more active learning formats during the basic science years. The medical curriculum continues to evolve at differing rates across schools. Many "innovations" have become part of the curricular repertoire; for example, medical schools have incorporated educational formats, such as problem-based learning or computer-assisted instruction, which emphasize active student learning, although in a number of cases they are limited to a small portion of the curriculum. In addition, the availability of clinical experiences during the first 2 years of the curriculum, especially those located in ambulatory settings, gives students an early glimpse of the world of actual medical practice. The use of standardized patients provides system and structure in the teaching and evaluation of clinical skills. Therefore, a look at medical education as a whole in the historical context reveals many positive changes (for example, an increase in student diversity over time, the introduction of alternative instructional formats, and attempts to evaluate student clinical competence more reliably). Within the context of environmental expectations, however, many challenges still remain. Medical schools are experiencing pressure to solve perceived problems with the specialty distribution of their graduates and with the specialty distribution of the general physician population, even though factors outside the control of the medical school, such as reimbursement and the practice environment, also influence specialty choice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8350450 TI - Improving access to health care through physician workforce reform. Directions for the 21st century. PMID- 8350449 TI - The elusive generalist physician. Can we reach a 50% goal? AB - National attention has focused on the goal of attaining 50% primary care practitioners to facilitate patient access and cost-effectiveness. To determine how long it might take to achieve this goal, we used the Bureau of Health Professions' aggregate physician supply model to forecast the generalist specialist balance. Assuming that 30% of graduates will enter generalist practice after 1993 (the percentage in the mid-1980s), the number of generalists would increase from 174,940 in 1990 to 232,000 in 2040 (77 per 100,000 population), but the percentage would remain at about 30%; specialists would continue to make up about 70% of all active physicians, but their total number would grow from 345,600 to 537,000 (178 per 100,000 population). If 50% of graduates were to enter generalist practices, by the year 2040 the number of generalists would grow to 373,000, or 124 per 100,000 (48.4% of all physicians). If entry into generalist practice falls to 20%, as suggested by recent medical student preferences, the number of generalists would peak at 192,000 (26.4%) in 2010 and would fall to 160,000 (21%) by 2040, resulting in 53 generalists and 201 specialists per 100,000 population. We discuss the implications of these findings on aggregate physician supply and on policy initiative affecting the ratio of generalists to specialists. Reform proposals affecting the specialty mix should clearly identify the desired future ratio of generalists and specialists per capita. PMID- 8350451 TI - Reforming graduate medical education. Summary report of the Physician Payment Review Commission. PMID- 8350452 TI - Comparing physician workforce reform recommendations. PMID- 8350453 TI - US medical school finances. PMID- 8350454 TI - 25 years in continuing medical education. The silver anniversary of the AMA PRA. PMID- 8350455 TI - The Maintenance of Competence Program of the Royal College of Physicians and Surgeons of Canada. PMID- 8350456 TI - Allied health accreditation faces major changes. PMID- 8350457 TI - The mammalian medical center for the 21st century. PMID- 8350458 TI - Potential impact of health system reform on medical education. Task Force on Health Systems and Medical Education. PMID- 8350459 TI - Medical workforce planning and medical education. Attaining consensus. PMID- 8350461 TI - Medical education and financial assistance programs sponsored by US government agencies. PMID- 8350460 TI - Medical schools in the United States and Canada. PMID- 8350462 TI - The lesson. PMID- 8350463 TI - How to avoid being manipulated by patients: notes from the county jail. PMID- 8350464 TI - [Evaluation of the renal function during hypotensive anesthesia induced by nitroglycerin, prostaglandin E1 or nitroglycerin+prostaglandin E1]. AB - We investigated the renal function perioperatively in 32 female patients who underwent mastectomy with hypotensive general anesthesia induced by nitroglycerin (NG), prostaglandin E1 (PGE1) and NG+PGE1. Urine output in PGE1 group (11 patients) was significantly larger than that in NG group (9 patients). It could be attributed to the increase of glomerular filtration rate. On the other hand, the value of beta 2-microglobulin in urine in NG group and the value of N-acetyl beta-D-glucosaminidase in urine in NG+PGE1 group (12 patient) were abnormal in some patients. These changes were not significant, but the disturbance of renal tubule could be possible. In summary, PGE1 was effective in the maintenance of the renal function. PMID- 8350466 TI - [Effects of prostaglandin E1 on temperature gradients between hand and foot during epidural anesthesia]. AB - We studied the effects of prostaglandin E1 (PGE1) on hand-foot temperature gradients (foot temperature-hand temperature) induced by lumbar epidural anesthesia. Thirty-six ASA class 1 patients undergoing rotatory acetabular osteotomy were randomly assigned to receive 0 gamma (n = 13), 0.005 gamma (n = 10) and 0.02 gamma (n = 13) of PGE1. Thermometric probes were placed on the palm and sole of each patient. Bladder temperature was also monitored to evaluate the change of core temperature. Epidural catheter was indwelled at the level between L2 and L3 prior to induction and 2 % lidocaine was administered epidurally. All patients were warmed by water blanket at 37 degrees C and fluids for infusion warmed at 37 degrees C. Humidity and moisture exchanger was placed in breathing circuit. Hand-foot temperature gradients of patients given 0 and 0.005 gamma of PGE1 increased to 2.8 +/- 1.5 and 2.3 +/- 2.3 degrees C at extubation, respectively. In contrast, temperature gradient of patients given 0.02 gamma of PGE1 was 0.0 +/- 1.8 degrees C (P < 0.01). There was no difference among the values of bladder temperature in each group. The effects of PGE1 on mean arterial pressure, heart rate and central venous pressure were minimal. These data suggest that 0.02 gamma of PGE1 administration is effective to reduce hand-foot temperature gradient during epidural anesthesia. PMID- 8350465 TI - [Does rate of urine flow influence the difference between bladder temperature and nasopharyngeal temperature during cardiac surgery with cardiopulmonary bypass?]. AB - Recently, bladder temperature (BT) monitoring is employed instead of rectal temperature because it is possible to keep the probe clean. The relationship between BT and core temperature is different in patients with steady state compared with those with rapid changes in temperatures. This study evaluated BT compared with nasopharyngeal temperature (NPT) reflecting brain temperature during cardiac surgery with induced hypothermia using cardiopulmonary bypass. During the steady state, after induction of anesthesia and immediately before cooling or rewarming, BT was equivalent to NPT independent of urine flow rate. In rapid cooling or rewarming phase of cardiopulmonary bypass, BT was not equivalent to NPT. BT preceded NPT in case of a very high urine flow rate, and with a lower urine flow rate delayed BT lagged behind NPT. During rapid changes in core temperature during cardiopulmonary bypass, the difference of BT to NPT depends on urine flow rate. PMID- 8350467 TI - [Interaction of midazolam and thiopental in amnestic effect]. AB - Interaction of midazolam and thiopental in amnestic effect was studied in 30 adult patients who underwent elective surgery of lower extremities under epidural or spinal anesthesia in combination with oxygen, nitrous oxide and low concentration of sevoflurane. Combination of midazolam 2.0-3.0 mg (0.041 +/- 0.006 mg.kg-1) and thiopental 3-5 mg.kg-1 produced amnestic effect in 87% of patients. No side effects, such as decrease in O2 saturation, upper airway obstruction, cardiovascular depression and delayed emergence were observed with this small dose of midazolam. Administration of midazolam 2.0-3.0 mg before epidural, or spinal anesthesia in the operating room under observation of anesthesiologists, followed by thiopental 3-5 mg.kg-1, was safe and comfortable to the patients. PMID- 8350468 TI - [Left ventricular function during hypoxia--II: Effects of intramyocardial pH]. AB - We investigated the effects of intramyocardial acidosis on cardiac function during hypoxia in mongrel dogs (n = 50). Intramyocardial pH in subendocardium of left ventricle was measured continuously using a pH electrode. During hypoxia (PaO2 = 20 mmHg) caused by inhalation of low oxygen fraction, intramyocardial pH decreased significantly following initial enhancement. Intramyocardial pH correlated significantly with arterial pH, base excess, lactic acid (LA) levels, coronary venous PcO2, and coronary venous-arterial PcO2 difference. There were significant correlations between intramyocardial pH with maximum rate of rise of left ventricular pressure (LV dp/dt max), left ventricular end-diastolic pressure (LVEDP), LVEDP/LVP and the time constant of exponential isovolumic left ventricular pressure fall. High arterial LA levels tended to cease myocardial LA uptake and production, turning LA balance into zero. LV dp/dt max was low in such a condition. Myocardial LA production decreased intramyocardial pH, but LV dp/dt max was maintained at high levels of LA production. These observations suggest that myocardial LA production maintains left ventricular function with the increase of ATP by acceleration of anaerobic glycolysis. In conclusion, during hypoxia, intramyocardial acidosis was caused by the increase of arterial LA level, myocardial anaerobic glycolysis and ATP breakdown, and it worsened left ventricular contractile function and relaxation. Arterial LA levels can play a major part in intramyocardial acidosis, but the increase in myocardial LA production might be beneficial to left ventricular contractile function. PMID- 8350469 TI - [Influence of bilateral stellate ganglion block on hemodynamics]. AB - This study was designed to investigate the influence of bilateral stellate ganglion block (SGB) on hemodynamics in 15 mongrel dogs. Following general anesthesia, each dog received SGB with 1.5% mepivacaine. Cardiovascular effect of bilateral SGB was assessed by measuring mean artery pressure (MAP), heart rate (HR), cardiac output (CO), right atrial pressure (RAP), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP) and common carotid arterial blood flow (CCAF). These were measured directly by a Swan-Ganz catheter and ultrasonic blood flow meter, during the first 15 minutes after SGB. A decrease of MAP and HR was observed after bilateral SGB. CO decreased for 13% compared with the control value. However, this change was not statistically significant. There was a significant increase in the bilateral CCAF, but the degree of the increase of CCAF was greater after unilateral SGB than after the bilateral SGB. PMID- 8350470 TI - [Influences of anesthetic method on post-cholecystectomy pain--a comparison between epidural and general anesthesia]. AB - This study was designed to compare the influence of epidural anesthesia with that of general anesthesia on postoperative pain state and management. We studied 16 patients who underwent elective laparotomy-cholecystectomy with epidural anesthesia without general anesthesia or with general anesthesia (nitrous oxide isoflurane). Following bolus epidural injection with 3 micrograms.kg-1 of buprenorphine in 0.25% bupivacaine 4-7 ml at the end of surgery, all patients received continuous epidural buprenorphine administration at the rate of 12 micrograms.h-1 for 48 hours. Pain relief was assessed for 72 hours after surgery using visual analogue scale. Postoperative rest pain of the epidural group remained at a lower state of pain than that of the general anesthesia group not only for 48 hours (P < 0.005) but also until 72 hours (P < 0.005) after surgery. We concluded that the epidural anesthesia produces a greater postoperative pain relief than general anesthesia. PMID- 8350471 TI - [Anesthetic management of a patient with Alzheimer's disease]. AB - We gave anesthesia to a 60-year-old female patient in stage III (end stage) of Alzheimer's disease for sigmoidectomy. She had myoclonus and parkinsonism and it was not possible to communicate with her verbally. After induction of anesthesia with thiopental, she had a catheter inserted into epidural space. Without endotracheal intubation, anesthesia was maintained with nitrous oxide, oxygen and isoflurane under spontaneous ventilation supplemented with mepivacaine from the epidural catheter. No muscle relaxant was used. Recovery from the anesthesia was uneventful. No complication was observed during anesthesia and postoperatively. PMID- 8350472 TI - [Anesthetic management of a patient with carcinoid syndrome]. AB - Anesthetic management of a 75-year-old female with carcinoid syndrome is reported. She had a tumor on the ileum and multiple metastatic tumors in the both lobes of the liver. Levels of both plasma serotonin and urinary 5-hydroxyindole acetic acid (5-HIAA) were significantly elevated before the operation. Although she was treated with somatostatin-analogue percutaneously, the levels of these hormones did not decrease significantly. The partial resection of the small intestine was scheduled under general anesthesia. Before induction of general anesthesia, hydrocortisone and ulinastatin were administered intravenously to prevent the release of chemical mediators. Anesthesia was induced with ketamine, diazepam, and vecuronium, and maintained with nitrous oxide, oxygen and enflurane. There was mild bronchospasm at the beginning of the surgery and the blood pressure was unstable during the operation, but anesthetic course was relatively uneventful. Although the patient recovered from anesthesia smoothly, she developed respiratory acidosis 45 minutes after extubation. She was intubated again and ventilated artificially with pressure support ventilation whose support level was 15 cmH2O for only three hours. We conclude that we should pay much attention not only during anesthesia but also after surgery, especially to respiratory system in patients with carcinoid syndrome. PMID- 8350473 TI - [A case of abortive malignant hyperthermia during funnel chest surgery]. AB - We experienced a case of abortive malignant hyperthermia during funnel chest surgery. Although a 5-year-old boy had muscle rigidity after the intravenous injection of succinylcholine chloride, the tracheal intubation was easy. The boy had high body temperature, metabolic acidosis, hyperkalemia and myoglobinuria during nitrous oxide-oxygen-sevoflurane anesthesia. We immediately came to the diagnosis of abortive malignant hyperthermia, gave intravenous injection of dantrolene sodium and started body surface cooling. Postoperative course was uneventful. It is necessary to pay a particular attention to possible malignant hyperthermia in patients with funnel chest surgery. PMID- 8350474 TI - [Perioperative management of patients on long-term administration of psychotropic drugs]. AB - We experienced perioperative management of thirty two surgical patients complicated with either schizophrenia or depression on long-term administration of psychotropic drugs during a period of three years from 1989 through 1991. They underwent various operative procedures under either general anesthesia or epidural anesthesia. Mental confusion was most frequently encountered in immediate postoperative period. The longer the patients had been treated with psychotropic drugs, the more postoperative complications were observed. We lost four patients within two weeks postoperatively. They all underwent laparotomy and had been treated with psychotropic drugs for a prolonged period. No significant association between the types of anesthesia and postoperative complications was observed. Surgical patients on long-term administration of psychotropic drugs should be managed carefully particularly during postoperative period. PMID- 8350475 TI - [A case of pulmonary alveolar proteinosis--evaluation of a Swan-Ganz catheter in bilateral lung lavage]. AB - Lung lavage, known to be effective for alveolar proteinosis, brings about significant hypoxemia immediately after evacuation of lavage fluid. Impeding blood flow of even a distal branch of a pulmonary artery by using a Swan-Ganz catheter (SGC) successfully prevented this hypoxemia. And this SGC procedure could be safely carried out to make lavage of each lung successively in one day. PMID- 8350476 TI - [Anesthetic management of a patient for giant pulmonary bulla drainage]. AB - Recently it is claimed that the drainage procedure may be a useful method for giant pulmonary bulla in compromised patients. We reported the anesthetic managements of three patients with giant bulla for these procedures. We chose epidural anesthesia in order to prepare for the postoperative analgesia and the expansion of surgical procedure. In selecting circulatory support method, care was taken to choose dobutamine that would cause no suppression of hypoxic ventilatory drive. There is no doubt that right ventricular function is particularly important in patients with chronic obstructive lung disease. We measured right ventricular ejection fraction by thermodilution method and end tidal CO2 by nasal cannula. These measurements may be useful methods for perioperative monitoring. PMID- 8350477 TI - [A severe case of reexpansion pulmonary edema in an asthmatic patient]. AB - A 60-year-old man with poorly controlled bronchial asthma was proposed for an emergency appendectomy. His preoperative chest X-P revealed that his left lung was completely collapsed with pneumothorax, but its onset was unclear. Following the left thoracocentesis, appendectomy was performed under general anesthesia (oxygen-halothane). About one hour after the thoracocentesis, pinkish foamy tracheal secretion was massively drained and its protein concentration was 3.8 g.dl-1.PaCO2 was 95 mmHg and PaO2 was 69 mmHg (FIO2 1.0). His chest X-P showed signs of pulmonary edema in his left lung and infiltrating shadow was observed in his right lung. IMV with PEEP, aminophylline and prednisolone improved his respiratory status and on the 11 th day he was weaned from the respirator. In a case of pneumothorax with unclear duration like ours, it is necessary to consider the possibility of the reexpansion pulmonary edema. PMID- 8350478 TI - [Severe theophylline toxicity in a pregnant asthmatic patient]. AB - A 32 year old pregnant woman who had taken large doses of theophylline for asthmatic attack was brought to our emergency medical center with convulsion and respiratory disturbance. Serum theophylline concentration was 52 micrograms.dl-1 on admission. We intubated the patient to control convulsion and respiration and performed cesarean section. Serum theophylline concentration of the newborn was almost at the same level as that of her mother. Baby was placed on ventilator for several days and discharged without trouble. We must consider the pregnancy as a major risk factor of theophylline toxicity. PMID- 8350479 TI - [The anesthetic management of cesarean section for multiple pregnant patients]. AB - Anesthetic management of cesarean section for twenty multiple pregnant patients, who were pregnant with triplet or quadruplet, was compared with that for 325 single pregnant patients and 21 twin pregnant patients. For anesthetic methods, spinal anesthesia was chosen most frequently in the multiple pregnant patients, as in single and twin (more than 75 percent). In multiple pregnant patients, the incidence of emergency operation was less. In multiple pregnant patients who received spinal anesthesia, gestational age was lower; birth weight was lighter; length of fundus uteri was longer; and blood loss including amniotic fluid was larger. In triplets, the third infants' UID-time was prolonged and their Apgar score was lower. PMID- 8350480 TI - [The sprotte needle decreases the incidence of postspinal headache]. AB - Postspinal headache (PSH) is the most frequent complication of spinal anesthesia. The factors responsible for the development of PSH include needle size, shape of the needle tip, patient's age, sex, infusion volume and period of resting. The purpose of this study is to compare the incidence of PSH between two different types of needle, Sprotte needle and Quincke needle. The Sprotte needle is characterized by a round profiled tip equipped with a lateral orifice. Our investigation by questionnaires revealed that the incidences of PSH after using either 22G Sprotte needle or 21-25G Quincke needle were 0% and 38.8%, respectively. We conclude that the Sprotte needle decrease the incidence of PSH. PMID- 8350481 TI - [A newly devised bandage for hemostasis after vascular puncture]. PMID- 8350482 TI - [A suggestion to prevent misuse of drugs]. PMID- 8350483 TI - [Reevaluation of spinal anesthesia in elderly people--an evaluation of circulatory changes]. AB - Appropriate methods of anesthesia for the elderly people are being discussed as the ratio of elderly people in our society increases. During spinal anesthesia, hypotension was frequently observed in patients with hypertension, arteriosclerosis, coronary deficiency, and so on. It is also difficult to pass the needle between degenerated vertebrae. However, general inhaled anesthesia accompanies the respiratory complications and consciousness derangement after surgical operations more frequently than after spinal anesthesia. In this study, circulatory conditions during spinal anesthesia in elderly people (30-91 years old) were analyzed in 109 cases of spinal anesthesia. Hypotension occurred about 10 minutes and 40-60 minutes after injection of anesthetics and was frequent in patients of high aged group, but tachycardia was not observed among them. In addition, their blood pressure in the recovery room could not recover to the level before anesthesia. It is thought that hypotension during spinal anesthesia was induced by the vascular dilatation caused by sympathetic nerve block and the deficiency of reflective venous constriction in upper extremities and abdominal organs. Tachycardia may also produce hypotension. However, the reflexive vasoconstriction and tachycardia are thought to be poor on account of arteriosclerosis and down regulation of beta-receptor in elderly people. Therefore, during spinal anesthesia in the elderly people, the catecholamine released by the surgical stimulation could not increase blood pressure effectively. To prevent hypotension during spinal anesthesia in elderly people, it is advisable to employ the treatment for upregulation of beta-receptor before anesthesia and the administration of alpha . beta-receptor, epinephrine and dopamine for control of blood pressure during spinal anesthesia. PMID- 8350485 TI - [Anesthesia with epidural spinal cord stimulation--I). Its application to general anesthesia]. AB - Epidural spinal cord stimulation (SCS) has been used for the relief of pain. We tried to apply SCS for general anesthesia. The subjects were 76 patients, undergoing thoracotomy (3 cases), thoraco-laparotomy (4), laparotomy (57) and others (12). A monopolar electrode was introduced to the epidural space via a Touhy needle. The conditions of the electrical stimulation were 12.5-50 Hz, 1.0 ms and 2-8 V. The voltage was adjusted to give comfortable sensation to the patients. After the electrode had been introduced, induction of anesthesia and tracheal intubation were performed with thiopental, diazepam and pancuronium or vecuronium. Anesthesia was maintained with nitrous oxide (70%-50%) and SCS. Nine patients inhaled low concentrations of enflurane in addition to nitrous oxide, and 39 patients received injection of vasodilators because of hypertension. All the patients were not awake during operation, and recovered their consciousness soon after the end of operations. SCS was continued for 17 hrs after operation. During 24 hrs after operation, 16 patients required no analgesics, 32 patients once and others twice or more. We conclude that SCS added to general anesthesia is useful to control pain, not only intraoperatively, but also postoperatively. PMID- 8350484 TI - [Combined spinal and epidural analgesia for caesarean section]. AB - We compared the combined spinal and thoracic epidural analgesia with 2% lidocaine for caesarean section, with spinal analgesia using 2% lidocaine, tetracaine or dibucaine, and also with lumbar epidural analgesia. The analgesia at high thoracic level could be achieved with combined spinal and epidural analgesia more easily than with others. The frequency of side effects with the combined spinal and epidural analgesia, such as hypotension, decrease of fetal heart rate and so on, was less than that with others. In conclusion, the combined spinal and thoracic epidural analgesia with 2% lidocaine is more useful for caesarean section, than the spinal analgesia or the lumbar epidural analgesia alone. PMID- 8350486 TI - [Heart rate response to intravenous atropine during cervical and lumbar epidural anesthesia]. AB - The authors evaluated the effect of cervical and lumbar epidural anesthesia on the heart rate response to intravenous atropine 0.01 mg.kg-1 in conscious humans with cervical epidural anesthesia (n = 40), with lumbar epidural anesthesia (n = 15) and without epidural anesthesia (n = 25). During cervical and lumbar epidural anesthesia using 1.5% lidocaine, levels of loss of cold sensation were C3-T7 and T7-S1, respectively. Heart rate increased by 14 +/- 10% (mean +/- SD) and 20 +/- 14% after intravenous atropine 0.01 mg.kg-1 in the patients with cervical and lumbar epidural anesthesia, respectively. These magnitudes of positive chronotropic effects were significantly less as compared with those in the patients without epidural anesthesia (32 +/- 11%). Nine of 40 patients (23%) with cervical epidural anesthesia showed heart rate increases of less than 3 beats.min 1 following atropine 0.01 mg.kg-1. And 30 of 40 patients (75%) required supplementary atropine 0.01 mg.kg-1 to increase heart rate for more than 20 beats.min-1 from baseline values. The present study suggests that the heart rate response to intravenous atropine is blunted in patients during cervical and lumbar epidural anesthesia, and that a larger dose of intravenous atropine may be required to accelerate the heart rate in most patients during cervical epidural anesthesia. PMID- 8350487 TI - Electron-equivalent dose for the effect of gadolinium neutron capture therapy on the growth of subcutaneously-inoculated Ehrlich tumor cells in mice. AB - The present in vivo study estimates the dose resulting from the gadolinium neutron capture reaction and the gadolinium enhancement extent of the thermal neutron effect. The assay is based on the time required from cell inoculation to the formation of tumors with an arbitrary size of 200 mm2. Mice were inoculated subcutaneously with Ehrlich tumor cells with or without meglumine gadopentetate (1.2 mg 157Gd/0.2 ml), and were exposed to 1.1 x 10(12) thermal neutrons cm-2(n 8), or 3 MeV electrons at three dose levels (each n 10). To reach 200 mm2 in size, it took 18.8 days for tumors treated with neutrons only and 34.7 days for those treated with gadolinium and neutrons. From the time-dose relation obtained with 3 MeV electrons, the equivalent doses corresponding to delays of 34.7 and 18.8 days were 15.0 and 7.4 Gy, respectively. Thus, gadolinium enhanced the thermal neutron effect two-fold (15.0/7.4) in the present study. PMID- 8350488 TI - Expressions of N-myc and ras oncogene products in neuroblastoma and their correlations with prognosis. AB - Thirty-six neuroblastomas were studied to determine the clinical significance of the N-myc gene product, N-myc, and the ras gene product, p21. The expressions of both gene products were analyzed immunohistochemically using formalin-fixed paraffin sections. Neuroblastoma cells were positive for N-myc expression in 13 cases and for p21 expression in 19 cases. N-myc expressions showed no significant relation to any clinical prognostic factor, whereas p21 expression was well correlated with clinical staging and Shimada's classification. There was a tendency for p21 expression to be low in N-myc(+) tumors, whereas p21 expression was frequently detected when N-myc expression was absent. The survival rate for N myc(-) patients was significantly higher than for N-myc(+) patients (P < 0.01). The survival rate for p21(+) patients was significantly higher than for p21(-) patients (P < 0.001). In addition, N-myc(+) and p21(-) patients showed a strong tendency towards a poor prognosis, whereas a combination of p21(+) and N-myc(-) indicated a good prognosis (P < 0.01). The results suggest that expressions of N myc and p21 detected by immunohistochemical staining could be among the most reliable prognostic indicators in neuroblastoma patients. PMID- 8350489 TI - A study of pharyngeal symptoms caused by bronchofiberscopy. AB - We investigated the occurrence of pharyngeal symptoms in 100 patients who had undergone bronchofiberscopies by conducting a post-examination survey of the patients. Eighty-four patients complained of having a problem. Seventy-five patients, including 26 with dysphagia, complained of pharyngeal symptoms. The proportion with pharyngeal symptoms whose symptoms appeared on the day of examination was a high 89.4%. In 70.6% of cases, the duration of symptoms was less than four days. The pharyngeal symptoms were particularly common among patients who had undergone a bronchofiberscopy on a previous occasion or whose examination lasted for 15 min or more. A greater dysphagia incidence was noted among patients who had required an endotracheal tube (P = 0.03) and among those whose examination had lasted for 15 min or more (P = 0.01). Based on the results, we are now studying methods of alleviating pharyngeal symptoms, including dysphagia. PMID- 8350490 TI - Bone marrow transplantation for hematological diseases in Hokkaido--June 1985 to December 1991. AB - Bone marrow transplantation (BMT) was started in Hokkaido in 1985. In the present report we have reviewed the clinical outcome of patients treated with BMT for hematological diseases in Hokkaido. Fifty-eight allogeneic and 19 autologous transplants were registered by December 1991. The underlying diseases consisted of 47 leukemias, 14 lymphomas, 10 aplastic anemias and six myelodysplastic syndromes. Among the allogeneic BMT cases, 55 were human leucocyte antigen (HLA) identical and three were mismatched. Among the autologous BMT patients, two received their marrow purged with 4-hydroperoxycyclophosphamide and five, with monoclonal antibodies and complements. The conditioning regimens used for malignancies were chiefly cyclophosphamide (CY) plus total body irradiation, or busulfan plus CY. In many cases, cytokines were used for rapid recovery of decreased leukocytes. Engraftment was observed in 50 out of 52 evaluated allogeneic and 18 out of 19 autologous transplants. Ten allogeneic patients suffered from severe acute graft-versus-host diseases (GVHD), and extensive chronic GVHD appeared in 16 patients. Relapses were observed in four cases of allogeneic BMT and six of autologous BMT. The major complications were interstitial pneumonitis (IP) and severe infections. Long-term survival rates were almost 60% in both allogeneic and autologous transplants. Mild acute GVHD and limited chronic GVHD increased the survival rates. The results indicated that substantial problems such as GVHD, IP and relapses must be controlled in the near future for an improved outcome to be made possible. PMID- 8350492 TI - Interhospital differences in cancer survivals in Japan. The Research Group for Population-based Cancer Registration in Japan. AB - The present study was an investigation of variations in cancer survival rates among hospitals in Japan, focusing in particular on the number of hospital beds as an institutional characteristic. Using data from 11 population-based cancer registries, the three-year survival rates for stomach cancer (n 1665), colorectal cancer (n 1090) and lung cancer (n 895) patients diagnosed in 1985 were calculated according to three different hospital categories (100-299, 300-499, 500+ beds). Cox's proportional hazards model was conducted, with adjustments for sex, age, clinical stage at diagnosis and treatment status, excluding patients who had been detected by screening (asymptomatic cases). The stomach and lung cancer patients treated in small hospitals (100-299 beds) were at a significantly higher risk of death than those treated in large hospitals (500+ beds) (hazard ratio (HR) = 1.36, 95% confidence interval (CI) = 1.11-1.65; HR = 1.41, 95% CI = 1.13-1.77, respectively). Similar findings were observed among colorectal cancer patients although they were not statistically significant. The findings can provide some information useful for the development of future public health policies aimed at controlling cancer mortality rates in our country. PMID- 8350494 TI - [An approach to evaluation methods for laboratory work]. AB - Evaluation methods were proposed for quality control, normal range calculation and laboratory diagnosis. As a quality control method, the Xbar-R control chart should be evaluated with an error detection chart or with operating characteristic functions. Normal range calculation was evaluated by three parameters, accuracy, precision and robustness which represents stability against abnormal data contamination. Prior to evaluating the laboratory diagnosis, patient data were plotted on a three dimensional chart, a star map, to determine whether apparent clusters were formed. Laboratory diagnosis is a process of reduction of multivariate medical information, and it develops new parameters related to the pathological state of the patient. The method was evaluated using entropy calculation or average count of abnormal parameters. PMID- 8350491 TI - Anticarcinogenic activity of green tea polyphenols. AB - The main physiologically active polyphenol in green tea extract is (-) epigallocatechin gallate (EGCG). Green tea extract has an advantage over EGCG as a cancer chemopreventive agent for humans, as is apparent from the Japanese custom of injesting green tea on a daily basis. Green tea extract similarly inhibited protein kinase C activation by teleocidin, a tumor promoter, as did EGCG. In addition, EGCG and green tea extract showed inhibitory effects on the growth of lung and mammary cancer cell lines with similar potencies. An experiment using the estrogen-dependent MCF-7 cell line showed the mechanisms of action of these compounds to be inhibiting the interaction of estrogen with its receptors. Considering our previous results of a single application of EGCG to mouse skin inhibiting the specific binding of 3H-12-0-tetradecanoylphorbol-13 acetate (3H-TPA) and 3H-okadaic acid, we postulated that EGCG and compounds in green tea extracts would block the interaction of tumor promoters, hormones and growth factors with their receptors: a kind of sealing effect. The sealing effect would account for reversible growth arrest, and may be induced by various kinds of compound. PMID- 8350493 TI - Laryngeal metastasis from a pulmonary papillary adenocarcinoma: a case report. AB - Metastases to the larynx from distant primaries are very rare. The present article reports a case of metastatic papillary adenocarcinoma of the larynx of lung origin. The patient was a 59-year-old female non-smoker, who had a history of adenocarcinoma of the right lung. For the laryngeal tumor, we performed a partial laryngectomy following biopsy. The tumor of the larynx was a papillary adenocarcinoma resembling the lung tumor, both demonstrating positive immunohistochemical staining for pulmonary surfactant apoprotein. The findings emphatically indicated the laryngeal tumor to be metastasis from the primary papillary adenocarcinoma of the lung. The present case report presents the clinical findings, course of disease and histopathological findings with brief reviews of the literature. PMID- 8350495 TI - [Standardization in clinical laboratory--its national and international activities]. AB - In order to obtain comparability among laboratory results obtained by different laboratories, standardization is necessary in all steps related to clinical laboratory practice. Standardization in clinical laboratory is a consensus process among professional, industrial and governmental organizations. Everyone concerned in clinical laboratory practice should try to follow those consensus proposed. The International Organization for Standardization (ISO) is a key international body which is represented by many different national organizations. World Health Organization (WHO) plays an important role in medical field, but many non-governmental organizations (NGO) such as the World Association of Societies of Pathology (WASP), the International Federation for Clinical Chemistry (IFCC) and others also contribute significantly. In 1975, the National Committee for Clinical Laboratory Standards (NCCLS) was established in USA and has been the most active. In 1985, The Japanese Committee for Clinical Laboratory Standards (JCCLS) was established as some other CCLS in different European countries. National activity for establishing many reference materials in Japan is briefly reviewed. PMID- 8350496 TI - [Thyroid diseases after Chernobyl accident]. AB - Radioactive iodine is released at every atomic-bomb testings and nuclear plants accidents and radioactive iodine is taken up by thyroid glands (internal radiation). In addition to the internal radiation, radioactive fallout causes the external radiation and thyroid glands are known to be sensitive to the external radiation. Furthermore, patients with radiation-induced thyroid disease can survive for a long time regardless of the treatment. The survey of thyroid diseases, therefore, is very sensitive and reliable ways to investigate the effects of radiation caused by atomic bomb explosion, testing and various types of nuclear plants' accidents. Our group from Nagasaki University was asked investigate the thyroid diseases and joined to the Sasakawa Project. In order to investigate the effects of radiation on thyroid disease, it is essential 1) to make a correct diagnosis in each subject, 2) to calculate a correct radiation dose in each subject and finally, 3) to find out the correlation between the radiation dose and thyroid diseases including age-, sex- and area-matched controls. We have established 5 centers (1 in Russia, 2 in Belarus, 2 in Ukraine) and supplied the most valuable ultrasonography instruments, commercial kits for the determination of serum free T4 and TSH level and for the autoantibodies, instrument for urinary iodine measurements, syringes, tubes, refrigerators, etc. We visit each center often and asked peoples at centers to come to Japan for training. Protocol of investigation is essentially the same as that in Nagasaki, and we are planning to investigate more than 50,000 children within 5 years. We are hoping to show a definite conclusion in the near future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350497 TI - [Basis of cytokines--history and present status]. AB - Cytokines are high molecular-weight substances which actively promote homeostasis and defend from exogenous agents. In 1965, Kasakura, et al, and Gordon, et al independently published articles describing an unknown substance (blastogenic factor) which was produced in the cultured media of lymphocytes and stimulated lymphocytic proliferation. In those days, since almost all immunologists believed that only antigens stimulated lymphocytic proliferation, the idea that this soluble factor actually had a positive role in lymphocytic proliferation was viewed suspiciously. Later, it was found that immune responses are constructed of mutual intercellular stimulations between T and B lymphocytes and macrophages. In the 1970s, several kinds of cytokines were found. Cytokines include lymphokines and monokines. These were named for substances produced from lymphocytes and monocytes, respectively. In 1972, at the second lymphokine workshop in Switzerland, a new term, "interleukin", was accepted as the name of an active substance which reacts mutually among leukocytes. Specific interleukins (IL) are numbered, e.g. IL-1, 2, 3 and so on. Later, a new term, BRM (biological responsive modifiers), was added to denote substances including not only cytokines but also other high weight molecules acting on various kinds of cells and tissues. Among the various kinds of cytokines, CSF (colony stimulating factor), Epo (erythropoietin), IL, TNF, and interferon are well known. In particular, CSF and Epo have been widely used for granulopenia and renal anemia with remarkable effects. PMID- 8350498 TI - [Erythropoietin determination in clinical medicine]. AB - Erythropoietin (EPO) is a prime stimulating factor for red cell production. EPO is a glycoprotein which has a molecular weight of 34,000, and is mainly produced by the kidney. EPO stimulates the differentiation and proliferation of erythroid progenitor cells in the bone marrow. The rate of production of EPO is regulated primarily by renal oxygen availability. Because anemia reduces renal oxygen availability, anemic stress accelerates EPO production in the kidney. Recently, EPO has mainly been determined by radioimmunoassay. Serum EPO titer is usually inversely correlated with hemoglobin concentration, as typically shown in iron deficiency anemia. Serum EPO titers in aplastic anemia are much higher than those in iron deficiency anemia relative to the hemoglobin concentration. Serum EPO titers in anemia caused by malignancies sometimes differ considerably among patients. Serum EPO in renal anemia usually show low titers irrespective of the degree of anemia. Serum EPO titers in untreated polycythemia vera are lower than those in treated polycythemia vera or secondary polycythemia. Determination of serum EPO is useful in differential diagnosis of polycythemia vera. Recombinant human EPO has been used to treat various anemias including renal anemia, refractory anemia, anemia in malignancies and secondary anemia. Determination of serum EPO titers is also valuable in many other situations of clinical medicine. PMID- 8350499 TI - [Clinical application of new cytokines]. AB - Recent progress of molecular biology and gene technology has developed a novel approach of clinical treatment. Several recombinant cytokines are already applied to clinical field. In this symposium, I introduced clinical application of some cytokines including GM-CSF, interleukin (IL)-1 and IL-3. The clinical benefits of IL-1 are; 1) IL-1 has an anti-tumor effect especially on cutaneous lymphoma and brain tumors, and 2) IL-1 has a function as hematopoietic growth factor for very immature hematopoietic stem cells. In the clinical Phase I/II study, IL-1 has been shown to have anti-tumor effect on cutaneous T-lymphoma via immune mechanisms. The side effects of IL-1 were variable including fever, fatigue, skin redness and so on, but they were all tolerable. The clinical phase studies of GM CSF and IL-3 are now on going. The preliminary studies show that GM-CSF has granulo-poietic activity but not thrombo-poietic activity, and that IL-3 has multi-hematopoietic activity. These cytokines may be useful for treatment of disorders of hematopoietic stem cells such as aplastic anemia and myelodysplastic syndrome. The side effects of both cytokines are resemble, but all are tolerable. PMID- 8350500 TI - [Cellular electrophysiological basis of proarrhythmic and antiarrhythmic effects of ischemia-related lipid metabolites]. AB - Lysophosphatidylcholine, an amphiphilic lipid metabolite, accumulates in the ischemic myocardium and plays a pivotal role in the production of arrhythmias. To clarify its cellular ionic mechanism(s), we investigated the effect of 1 palmitoyl-lysophosphatidylcholine (LPC) on the guinea pig ventricular myocytes, using whole cell- and patch-voltage clamp methods. In whole cell recordings, extracellular application of LPC (20-100 microM) depolarized the resting potential within several minutes and produced automatic action potential discharges from the resting and plateau potentials. Such effects were attributed mostly to the decrease in inward going rectifier K current (Ik1). Single channel recordings in the cell attached mode revealed that this decrease in Ik1 is secondary to the reduction of the single channel conductance and not due to decreased open probability. LPC (5-50 microM) also decreased the excitatory Na+ current (INa) in an all-or-nothing manner, depending upon the concentration used. Such decreases in the resting potential and peak INa could be responsible for the marked retardation of conduction velocity and therefore production of reentry. Another amphiphilic lipid metabolite, a long-chain acylcarnitine or 1 palmitoylcarnitine (PALC), had LPC-like depressant effects on INa, albeit the effect was reversible in the majority of cells tested. On the other hand, a short chain acylcarnitine, 1-propionylcarnitine (PROC) did not affect the INa by itself even at a high concentration (50-500 microM), whereas it prevented the LPC's depressant effect on INa. Like PROC, the middle-chain acylcarnitine, e.g., 1 hexanoylcarnitine (HEXC) did not decrease the INa, but prevented the LPC's deleterious effects on INa, albeit the latter effect was much weaker than that of PROC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350502 TI - [Physiology of cardiac performance]. AB - We previously proposed i) Emax (end-systolic maximum elastance of the ventricle) as an index of contractility independent of preload and afterload and ii) PVA (systolic pressure-volume area of the ventricle) as a measure of the total mechanical energy generated by the ventricular contraction. Emax is defined as the slope of the end-systolic pressure-volume relation, which is relatively linear within the normal working range of the left ventricle. A working pressure volume point starts from the end-diastolic pressure-volume curve, comes close to or slightly exceeds the end-systolic pressure-volume line, and returns to the end diastolic curve. Thus, the end-diastolic and end-systolic pressure-volume curves envelop a family of pressure-volume trajectories of variously loaded contractions in a stable contractility. Emax increases with enhanced contractility and decreases with depressed contractility. PVA is an area between the end-diastolic and end-systolic pressure-volume curves on the origin side of the systolic pressure-volume trajectory. PVA linearly correlates with myocardial oxygen consumption regardless of ventricular loading conditions in a given Emax and this load-independent oxygen consumption-PVA relation is elevated with an enhanced Emax. Consequently, Emax and PVA have proved to be key measures and concepts in the physiology of cardiac performance. PMID- 8350501 TI - [Molecular basis for cardiac functions]. AB - Cardiac functions are regulated by both contractile proteins and calcium regulatory proteins. Alterations of these are considered involved in impaired contractile and diastolic functions in hypertrophied hearts. In this study, we analyzed molecular changes during the development of cardiac hypertrophy. Cardiac hypertrophy was induced by constricting the pulmonary artery in rabbits or the aorta in rats. In rabbit right ventricular hypertrophy, protein synthesis was increased to 1.8 times the control 2-4 days after pulmonary constriction. This increase in protein synthesis could be classified as an increase in both capacity and efficiency of synthesis. beta-cardiac myosin heavy chain (beta-MHC) isoform was predominantly expressed and alpha-MHC was suppressed in pressure overload hypertrophy. The switch from alpha- to beta-MHC occurred at the mRNA level. Ca(2+)-ATPase of sarcoplasmic reticulum (SR) is important because it regulates intracellular Ca2+ levels during relaxation. In pressure-overload hypertrophy, the SR Ca(2+)-ATPase was markedly decreased in both the enzyme activities and mRNA levels, while in thyrotoxic hearts both were increased. Interstitial cells also undergo phenotypic modulation which was demonstrated by the induction of nonmuscle-type MHC in pressure-overload hypertrophy. The signal transduction system in cardiac hypertrophy was examined by stretching cardiac myocytes grown on deformable membranes. In our analysis, stretching myocytes stimulated protein kinase C, MAP-II kinase and S6 kinase, all of which may lead to the induction of fetal-type cardiac genes and accelerated protein synthesis. These analyses of subcellular adaptation in cardiac hypertrophy provide important insights into understanding molecular mechanisms of cardiac functions. PMID- 8350503 TI - [Morphological and functional study by echocardiography]. AB - Echocardiography can measure various parameters of left and right ventricle function during either systolic or diastolic phase. Many parameters of cardiac function are obtained by B-mode, M-mode and Doppler images. Recently, invasive techniques, such as trans-esophageal echography, intra-luminal echography, contrast echography of the left ventricular muscle and stress echography were developed. In the future, 3-dimensional echography and acoustic tissue characterization will be developed for quantitative measurement of cardiac functions. PMID- 8350504 TI - [A trial approach to the ideal control-management and systematization of clinical laboratory]. AB - Clinical laboratory examinations have continued to expand with the increase in demand for medical care. However, recent high-technology, medical care has made introduction of a new system of quality control in the clinical laboratory indispensable. First, regarding personnel (clinical laboratory technicians), reducing staff hours led to a drop in the employment of newcomers and subsequent aging of the staff. Next, introducing a system to save labor is extremely expensive, making the cost effectiveness very poor and consequently making it difficult to introduce such a system in many laboratories. This symposium was initiated to assist the search for ways in which the present clinical laboratory can survive despite rising personnel expenses and reagent costs, while reducing medical expenses. And at the same time developing a guide to establishing our ideal for the clinical laboratory of the 21st century. PMID- 8350505 TI - [The present situation of the computer system for the clinical laboratory in Japan]. AB - We report the present situation of the computer system utilization for the Clinical Laboratory in Japan. For this studies, the data were calculated to our purpose from the materials for statistics published by the Ministry of Health and Welfare, Japan Society of Medical Technologist, and so on. The results were as follows, 1) computer systems were used on the 85% of all hospitals, and the most of them were used for the medical office work included the payment office. At clinical laboratory, there was very few use the computer systems, which account for 25%. 2) In the field of the clinical laboratory, there was mostly used at clinical chemistry, next field was hematology, serology, urinalysis, and microbiology, respectively. 3) Total system for the hospital, including ordering system were used only 0.06% (208 cases) of all hospitals in Japan. We calculated the number of beds with a hundred thousand population, the spread of the computer system, the number of the out-patients, in-patients, and the utilization ratio of beds, then we compared with that data for all of the prefecture included Tokyo, Osaka and Kyoto. As a result of the calculation, the prefecture which the number of bed with a hundred thousand population was much more than another zone were the utilization ratio of beds was less than another area, and there was worth at the spread of computer system. We think there areas had the smaller hospitals than that of having highly spread of computer system. PMID- 8350506 TI - [Hardware]. AB - For effective management of clinical laboratory in spite of a shortage of medical technologists, we modified conventional analytical instruments on the market, and developed the automatic transport mechanism and the robotic analytical instruments to suit the operational needs of our laboratory. Consequently, we succeeded in designing a system in which the results for 89% of all the tests ordered were reported within 60 minutes after the time when the specimens were received at the laboratory. As a result of this laboratory automation system, medical technologists were spared from their routine work, and their expertise was now diverted to the other duties like examination for microbes in hospital facilities, evaluation for sterilization of surgical instruments, and maintenance of measuring apparatuses in the operating rooms. In addition, the technologists also became involved in preventive health activities for university personnel such as: periodical healthy check, and screening programs for adult diseases, and the like. Some became engaged in the health management programs for radiological department workers. Thus, the introduction of this laboratory automation system, enabled the medical technologists to cooperate in hospital operation activities and to contribute to the prevention of iatrogenic disorders. PMID- 8350507 TI - [Perspective for clinical laboratory management and its systematization--effects of the systematization of clinical laboratory management]. AB - There are a large number of ideas concerning the systematization of clinical laboratory management. Therefore many types of laboratory systems have been constructed. As our hospital is not large, we adopted a small scale laboratory system. In introducing it, we expected not only an increase in value-added labor productivity by automating laboratory tests, but also an improvement in technologist's cost awareness. Consequently, new system equipment has itself performed the former in many sections, but not the latter. Improvement in cost awareness was caused by the technologist's routine work in managing reagent and material stocks. We found that this soft-type systematization has been more important than the advanced hard-type system. PMID- 8350508 TI - [Future of administration and management in clinical laboratory]. AB - Some problems in administering and managing clinical laboratories relate to technology, safety and health. Total systematization will help resolve these problems, and includes several new ideas, such as total investigation, total automation, total safety, total flexibility, total standardization, total estimation and a totally open-door. Patient-orientation is also important. In our physiological department, this aim was obtained to some extent by the introduction of computerization, optical data filing system and personnel arrangement. PMID- 8350510 TI - [A clue for discovery and recent progress in gene abnormalities]. AB - With the striking progress in analytic technology for detecting gene abnormalities, genetic analysis, such as polymerase chain reaction (PCR), has become a routine procedure in laboratory medicine. Consequently, the role of laboratory medicine in detecting genetic disease is increasing. However, in the process of genetic analysis maintaining consistency with clinical expression is necessary. In this symposium, the discussion includes the following items: (1) Genetic analysis of Maple Syrup Urine Disease (MSUD), (2) Analytic study of abnormal antithrombin III (TOYAMA), (3) Diagnostic procedures for anemia attributed to RBC membrane protein abnormality, (4) Genetic analysis of LDH-M subunit deficiency, (5) Development of a new prospect for hereditary hyperlipidemia, (6) Genetic analysis of hormone resistance syndromes: T3 receptor abnormality, and (7) Etiologic genetic analysis of pituitary cretinism. In general, DNA analysis in these cases can demonstrate wide variations in gene structural abnormalities. In MSUD, for instance, enzyme abnormalities, which occur in enzyme complex of various kinds include E1 alpha, beta, or E2. Currently, the cell fusion method, and PCR-SSCP method, miss-match PCR-DGGE method and so on are commonly used analytic methods. To sum up the issues discussed at this symposium, the most important function of genetic analysis is to clarify the relationship between the many clinical phenotypic expressions and the essential abnormality in the structure of the gene and/or function of the controlling proteins. PMID- 8350509 TI - [Assay of erythropoietin in serum with short term enzyme linked immunosorbent assay method--the clinical significance: Part 2--:Relation to serum iron, UIBC and ferritin in renal failure and hematological disorders]. AB - With a newly developed short term enzyme linked immunosorbent assay kit (TOYOBO Co.), in which 2 kinds of anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from patients with renal failure and hematological disorders. In this report, the EPO data were analysed in relation to serum iron concentrations, with ferritin and UIBC. In the patients with renal failure, there was no significant correlation between EPO concentration and serum iron, ferritin, nor UIBC concentration. On the other hand, in the patients with hematological disorders, there were two types. One was in patients with iron deficiency anemia, whose serum EPO was negatively correlated to serum iron (r = 0.64) and ferritin (r = -0.59), but positively related to UIBC (r = 0.27). The another was the pattern in patients with aplastic anemia, leukemia and MDS, whose serum EPO positively correlated to iron and ferritin but negatively correlated to UIBC. In the patients with aplastic anemia serum EPO had good correlation to serum iron (r = 0.62), ferritin (r = 0.60) and UIBC (r = -0.46). The relationship of EPO to iron in the patients with leukemia (r = 0.54), and EPO to ferritin in the patients with MDS (r = 0.42) show significantly positive correlation coefficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350511 TI - [Gene analysis of maple syrup urine disease (MSUD)]. AB - Maple syrup urine disease (MSUD), an autosomal recessive hereditary metabolic disorder, is due to defective oxidative decarboxylation of the branched-chain alpha-ketoacids (BCKAs) derived from transamination of the three branched-chain amino acids, valine, leucine and isoleucine. The oxidative decarboxylation of three BCKAs is catalysed by the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. BCKDH consists of three catalytic components: E1, E2 and E3. The E1 component is further composed of two subunits, E1 alpha and E1 beta. To clarify the mechanisms involved in MSUD, measurements of the enzyme activity in cultured cells, measurements of the generation time in cultured cells, complementation analysis and immunoblot analysis were performed. To further elucidate the molecular mechanisms of MSUD, we and others isolated and characterized cDNAs encoding BCKDH-E1 alpha, E1 beta, E2 and E3. The human genome structures of BCKDH -E1 alpha, E1 beta and E2 were also characterized. Gene mutations in E1 alpha, E1 beta and E2, respectively, were identified at the molecular level in three cases of classical MSUD. It became clear that the molecular mechanisms of MSUD involved not only the function of each subunit but also the protein-protein interactions between each subunit. In an attempt to further analyse the molecular basis of MSUD, we carried out complementation analyses by somatic cell hybridization, and identified the affected component of BCKDH complex in the MSUD patient. Furthermore, to rapidly screen for gene mutations, we used PCR-SSCP analysis. Seventeen patients with MSUD were examined using these methods. Defects of E1 alpha, E1 beta and E2 subunits were suspected in 8, 5, and 4 patients, respectively, by complementation analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350512 TI - [Abnormal antithrombin III: abnormalities of heparin or protease binding domain]. AB - Two patients with abnormal antithrombin III manifested abnormality in heparin binding activity (abnormal antithrombin III "Toyma") or protease binding activity (abnormal antithrombin III "Aomori"). Antithrombin III "Toyama" is hereditarily homozygous with Arg47 to Cys47 (TGC-->TGT) mutation, and antithrombin III "Aomori" is hereditarily heterozygous with Arg393 to His393 (CGT-->CAT). The former is classified as type II-c, and the latter as type II-b according to Lane's classification2). Both patients showed cerebral thrombosis after age 20. Heparin cofactor II activity in the former case was slightly higher than normal. Oral anticoagulant therapy was used in the both cases. These cases were examined by biological and immunological assay, heparin sepharose column chromatography, binding activity to cultured porcine endothelial cells, restriction fragment length polymorphysm and polymerase chain reaction. The authors developed an antithrombin III assay method to be able to estimate real activity without the influence of heparin cofactor II activity11), and to apply the low molecular weight heparin to prevent relapse of thrombosis, and finally to find an anticoagulant substance in an interesting case of hepatocellular carcinoma (Edmondson type 1) producing normal antithrombin III30). PMID- 8350513 TI - [Erythrocyte membrane abnormality and hemolytic anemias]. AB - Screening for hemolytic anemia was established in Fukuoka University Hospital based on automated analyses of enzymes and glycolytic intermediates in suspicious blood specimens. Using the screening system, we found more than ten hemolytic anemias due to abnormalities of membrane proteins, glycolytic enzymes and hemoglobin in the last two years. In the present report, we summarize the screening system for hemolytic anemias and present two types of hemolytic anemia due to abnormalities of band 3 protein and deficiencies in band 4.2 protein. PMID- 8350514 TI - [Diagnostic clue and genomic analysis of LDH-M subunit deficiency]. AB - Lactate dehydrogenase (LDH) M(A) subunit deficiency was first discovered by urinary discoloration and a discrepancy of laboratory data. Since then, five other families with this disorder have been reported in the Japanese population. The response of pyruvate concentration after forearm ischemic work is specific for LDH-M subunit deficiency. During strenuous exercise ATP production is significantly impaired and muscle tissue is damaged. A genetic study revealed a deletion of 20 base-pairs in exon 6 of the LDH-M gene in four families that were homozygous and one family that was heterozygous for LDH-M subunit deficiency. This mutation results in a frame-shift translation and premature termination. In addition to this mutation, we found a nonsense mutation at codon 328 in exon 7 in an individual heterozygous for LDH-M subunit deficiency, and a deletion of 3 base pairs, TGT at codon 127 in exon 3 in a proposita who was homozygous and in her parents who were heterozygous for LDH-M subunit deficiency in the fifth family. Therefore, molecular heterogeneities were revealed in genetic mutations of LDH-M subunit deficiency. PMID- 8350515 TI - [New approach to pathogenesis of genetic hyperlipoproteinemias]. AB - Genetic hyperlipoproteinemias are produced by defects or abnormalities of several enzymes, apolipoproteins and transfer proteins relating to lipoprotein metabolism. Abnormalities of the LDL receptor cause familial hypercholesterolemia (FH) and the deficiency of cholesteryl-ester transfer protein (CETP) causes familial hyperalphalipoproteinemia. Here, abnormalities of the LDL-receptor genes and CETP gene are described. More than 70 mutants of LDL-receptor gene have been reported, and we discovered 4 mutants in the Hokuriku district of Japan. Compared with FH-Tonami-1, FH-Tonami-2 showing a partial defect of the LDL-binding domain of the receptor, is a genetically determined mild type of FH. Only 10% of the LDL receptor abnormalities in FH have been clarified, and the causes of the remaining 90% are unknown at present. CETP catalyzes the transfer of cholesteryl ester from HDL to other lipoproteins. We found a familial hyperalphalipoproteinemia produced by the CETP deficiency. A point mutation in the splice donor site of intron 14 in the CETP gene was found in all Japanese patients with CETP deficiency. CETP deficiency produces an antiatherogenic lipoprotein profile in high HDL cholesterol level and low IDL- and LDL-cholesterol levels. We developed a rapid screening method for the splicing defect of CETP gene, by means of primer specific restriction map modification. The frequency of the mutated allele in the general population was estimated to be 0.81%, and the mutant was frequent in Japanese subjects with hyperalphalipoproteinemia. In summary, the detection of gene abnormalities is essential for understanding lipoprotein abnormalities and clinical manifestations in genetic hyperlipoproteinemias. PMID- 8350516 TI - [Genetic analysis of hormone resistance]. AB - Thyroid hormone resistance is a syndrome defined as impaired tissue response to thyroid hormone which would be excessive under normal circumstances. Although it has long been speculated that this defect was caused by an abnormality at the site of the nuclear receptor for thyroid hormone, isolation of complementary DNA encoding thyroid hormone receptors has only recently enabled us to directly examine this hypothesis. Thyroid hormone receptors are coded on two separate genes, THRA and THRB. Both genes give rise to multiple receptor subtypes through alternative splicing or different usage of promoters. Tight linkage between THRB locus and resistant phenotype was demonstrated in one affected family, and subsequently, more than 30 genetic abnormalities of the THRB gene were isolated. No abnormalities have been demonstrated on the THRA gene. Denaturing gradient gel electrophoresis was used to screen abnormalities on the THRB gene of affected families, and the results also strongly supported the hypothesis that thyroid hormone resistance is caused by an abnormal THRB gene. Molecular analysis of thyroid hormone resistance will facilitate understanding of the pathophysiology of this syndrome and the molecular mechanism of thyroid hormone action. PMID- 8350517 TI - [Molecular pathology of congenital pituitary hypothyroidism--discovery of new clinical entities]. AB - Congenital pituitary hypothyroidism (pituitary cretinism) results in severe mental and growth retardation when it is not treated soon after birth. Since the introduction of neonatal mass screening of thyrotropin (TSH), most congenital hypothyroidism has been detected except for pituitary and hypothalamic hypothyroidism. In 1971, we reported the first familial case of congenital isolated TSH deficiency and thereafter began intensively investigating the molecular pathology of congenital pituitary hypothyroidism. After determining the entire structure of the human TSH beta gene, we identified the molecular pathology in this patient. Recently, we reported a familial case of congenital combined pituitary hormone deficiency (PIT1 abnormality). To examine the PIT1 gene, which encodes pituitary specific transcription factor, Pit-1/GHF-1, we determined its genomic structure. Sequence comparisons using PCR amplified PIT1 gene sequences revealed only one nonsense mutation in the patient, and established that this alteration caused the combined deficiencies of TSH, GH and PRL. We also discuss other recent progress in molecular pathology of congenital pituitary hypothyroidism. PMID- 8350518 TI - [The past and future of the clinical microbiology]. AB - The purpose of clinical microbiology is to provide accurate information about microorganisms in a given specimen. This information is of significance to the patient as well as to the clinician. In this symposium, we discussed ways in which the microbiological laboratory has contributed to controlling infectious diseases as well as the advanced technology needed in the laboratory of the to future to quickly identify suitable chemotherapy. First, Dr. Kudo reviewed the past activities of microbiological laboratories. Then Dr. Machida, Dr. Okada and Dr. Kanno discussed the current situation and existing problems in clinical microbiology. Following that, Dr. Inamatsu presented a paper on the clinician's view of which microbiological examinations are useful inpatient treatment. Lastly, Mr. Sugahara discussed advanced technology in the field of clinical microbiology, and Dr. Kobayashi described the activity of microbiological laboratory as a part of an infection control unit in the hospital. PMID- 8350519 TI - [The role of the clinical microbiology laboratory in the past]. AB - Over the past 150 years, since Koch first isolated the tubercle bacillus, clinical microbiologists have used culturing techniques to demonstrate of the presence of pathogenic microorganisms associated with infectious diseases in clinical specimens. The development of medicine and chemotherapy and the improvement of sanitary conditions resulted in a marked decrease in infectious diseases. In stead of infections due to virulent pathogens, opportunistic infections in the compromised hosts by non-virulent or weakly virulent bacteria have been on the rise. As a result, determining the pathogenicity of an isolated bacteria becomes important. The past two decades have seen extensive efforts to exploit the potential of automation in clinical microbiology and to develop increasingly rapid procedures. New technology, such as molecular genetics, has also been introduced into clinical microbiology. For more correct and precise diagnoses of infectious diseases, the clinical microbiology laboratory should be enlarged as an "Infectious Disease Laboratory" to include an extended work on not only the detection of pathogens from the specimens of infectious disease, but also serodiagnostic tests and immunological tests of hosts. The "Infectious Disease Laboratory" would also play a key role in the control of nosocomial infection working with the infection control committee and infectious disease clinicians. PMID- 8350520 TI - [Current state and problems in the microbiology laboratory--organizing the laboratory]. AB - The microbiological laboratory in the hospital has many roles including the rapid and precise identification of pathogenic bacteria in specimens, their antimicrobial susceptibility tests, microbial antigen detection using immunological methods and DNA hybridization methods, surveillance of bacterial milieu of the hospital environment, monitoring quality control of microbiological methods, to educate microbiological skills of staffs, the economical management of laboratory and so on. The last two issues are our major concerns. Improvement of the microbiological skills of the staff is most important in the laboratory, but is a time-consuming. From our experience, a technical expert, intermediately skilled technicians and beginners should always work in the laboratory, together. On the other hand, the economical management of the microbiological laboratory is also another concern. Although the mechanization of procedures comes to mind, it is hard to improve the economical conditions in the laboratory. Because of the control of the machines is not completely automatic and requires the knowledges and decisions of technical experts, the work force and running cost can not be reduced. As the technical expert can economize in the use of media or tests for identification of pathogens, good training of beginners into skillful successors, is important. PMID- 8350521 TI - [Changes in causative agents and the limitations of microbiological technique]. PMID- 8350522 TI - [Usefulness of microbiological test in clinical decision making--from the view point of clinician]. AB - During the last 50 years, there have been changes in the types of infectious diseases causing death in Japan. Endemic diseases have decreased and nosocomial infection during the therapeutic course of various diseases have increased. Progress of various new medical technology for cancer therapy and transplantation are supported by developed infection control, and the target of microbiological tests has changed from endemic organisms to resident organisms. To manage infectious diseases, clinicians collect considerable information. Microbiological tests are only one part and sometimes are used to assess therapeutic results. In this situation, microbiological tests sometimes only reconfirm or guide changes in therapeutic strategy if the initial empiric therapy was inappropriate. Then, well designed statistical data are necessary for appropriate empiric therapy. Surveillance of hospital infection is another important role of the microbiological laboratory. To improve the functioning of the microbiological laboratory, we need not only automatic and rapid systems, but also effective communication with clinicians to respond to their needs with clinically useful data. PMID- 8350523 TI - [The development of an information network for new techniques in clinical microbiology]. AB - In accordance with changes in our life styles and our social and biological environment, the techniques and methods of clinical microbiology must change and develop. New techniques, such as selected zone culture, direct drug susceptibility test, ATP bio-luminescence assay on membrane filter and expiratory gas analysis are among these developments. To ensure equal development among medical laboratories, an information network concerning these new microbiological methods in needed. An enormous quality of information can be contained and managed usefully by a two dimensional bar-code system. Clinical microbiology must not only contribute to clinical medicine but also respond to changes in the social and biological environment, and must include cost effectiveness, and preservation of natural resources. Using the new techniques effectively and introducing automatic systems will facilitate practical, useful and rapid clinical microbiological diagnoses. PMID- 8350524 TI - [Clinical microbiology in the 21 century]. AB - The number of compromised patients has remarkably increased, with the recent advancement of medical treatment. This fact may account for the increase in the rate of hospital infection. Occupational infection of health care workers from blood-borne virus is another problem. During the recent increase in hospital infections, clinical microbiology laboratories in many countries performed expanded routine work and research. These situations were studied through questionnaires sent to countries with membership in the Hospital Infection Society. An inquiry into the tasks of clinical microbiology in the 21 century was made in order to establish more effective and useful system of the laboratories. PMID- 8350525 TI - [Turning point in quality control in Japan--current status & problems and future issues]. AB - Some authorities suggest that quality control in Japan is now at a turning point. During the 30 years since its introduction in the 1960s, quality control has improved dramatically, and a number of new quality control techniques have been designed and applied to routine examination. In actual practice, however, people tend to become insensitive to abnormalities or to ignore them, causing an increase in the number of abnormal results. This article will review a survey of quality control and describe the current status, problems and future issues in quality assurance. PMID- 8350526 TI - [Turning point in quality control: problems at present and themes in future]. AB - Quality control in clinical laboratory has a longer than forty-year history after its introduction. At present, quality control has been considered as one of essential tools to evaluate the quality of clinical laboratory data. However, several problems to be solved have still remained. I clarify the problems at present and declare the themes in future. Problems of internal quality control (IQC): Analytical precision of clinical laboratory test has remarkably improved recent years because of the advancement of technologies including analytical procedures and instruments. However, analytical accuracy has not attained the subjects. Furthermore, QC procedures have been converting into subjects and it has been generally considered that using a lot of QC material and QC method is a good manner. As a result, fundamental control procedures such as material control, reagent control and instrument maintenance have been ignored. Problems of external quality control (EQC): It has been considered that EQC serves as an indicator of analytical accuracy and shows the average analytical performance of all participants. However, some problems have remained as follows: (1) Problem of samples for proficiency testing. (2) Problem of classification of peer group. (3) Problem of target value. (4) Problem of evaluation criteria. In general, various IQC methods have been used without careful consideration. However, I would like to emphasize that we have to select the best QC method which can detect the error to be checked according to the method performance. For this reason, we have to grasp the purpose of QC and be careful to not change the subjects into the QC procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350527 TI - [Review of quality control program for clinical microbiology developed by the Tokyo Metropolitan Government]. AB - There are limitations or disadvantages in previous nation wide external quality control (QC) programs. Therefore, the Tokyo Metropolitan Government and the Tokyo Medical Association (TMA) initiated the first regional annual external QC program in 1982. The QC results in chemistry, hematology and immunology have shown rapid improvement. By contrast, some serious problems in microbiology have been revealed. METHODS AND RESULTS: The Tokyo Metropolitan external QC programs consist of so-called "open" and "blind" surveys. Simulated specimens were prepared for open and blind surveys and all laboratories were asked to examine the specimens using routine procedures. All participants were required to report not only their test results such as codes for computer analysis, but also to describe the process. Written answers included the following subjects, procedures, culture characteristics and others: number and type of selective media, incubation conditions, colonial morphology, microscopic and biochemical characteristics of the microorganisms, etc. The survey reports on the identification of some kinds of pathologic organism were inaccurate. Discrepancies between the number of media used for routine procedures and the number used in open survey were detected. CONCLUSIONS: Previous nationwide external QC programs using frozen-dried organisms have been valuable in promoting general improvement in clinical microbiology in Japan, but they have revealed only gross errors. Our 10-year experience has convinced us that additional important information is obtained when using simulated specimens for open and blind surveys. The turnaround time and other aspects of the reporting of results should be monitored. Due to possible legal ramifications of QC surveys, laboratories are now more afraid of making errors than before. The continuing education of laboratory personnel is essential. PMID- 8350528 TI - [Difficulties and problems in external quality control of immunoassay]. AB - Present status and problems in external quality control of immunoassays were described. Despite the increasing popularity of these methods, there are many difficulties in achieving good analytical performance. Consequently, immunoassay results demonstrate poor interlaboratory comparability. To exclude these difficulties, several changes should be made, for example, preparation of common reference standards, consent methods to give values to laboratory working standards, reference methods, matrix of test samples similar to actual clinical samples etc, before constructing suitable external quality control systems. PMID- 8350529 TI - [Significance and availability of small scale quality control programs]. AB - Characteristics of small scale or regional quality control (QC) programs are quick responses to resolving QC problems and cooperation. In this paper, we illustrated and discussed the positive results of the regional QC program in Shizuoka prefecture as a model for small scale QC assurance programs. Kitamura's allowable limitations for analytical error in internal QC were estimated from the physiological and technical variation of individual assays and compared with the coefficient of variation (CV) of each analyte in clinical laboratories. CV of analytes in 80% of the laboratories cleared Kitamura's allowable limitation with the exception of alkaline phosphatase and calcium. Many laboratories are now making extensive efforts toward clearing the allowable limitation in these two items. Many working groups (WG), such as enzymes, immunochemistry, and ion selective electrode WG, are very active in resolving problems found by QC programs. The results obtained in these working groups were effectively communicated to the clinical laboratories and bedside physicians. These responses in small QC program are surely complementary to large scale QC programs such as the QC program of the Japan Medical Association. PMID- 8350531 TI - [Quality assurance for histodiagnosis and cytodiagnosis with a model of proficiency testing]. AB - A quality assurance (QA) program for histopathology and cytology has not yet been completed although an inhouse quality control for technical standardization is being tested. The fact that a strict Performance Improvement Program of CAP (College of American Pathologists) for cytology is required separately from other laboratory tests emphasizes the importance of cytology, since erroneous cytology reports would directly cause incorrect clinical diagnosis. The results of questionnaires gathered by the QA Committee of the Japan Association of Registered Clinical Laboratories on preparation techniques, workload limits of pathologists and technologists, double diagnostic systems, error detection programs, and specialization of personnel are presented. In addition to pathology and cytology proficiency testing provided by CAP survey, a model of blind QC (quality control) in our laboratory is discussed; for diagnostic standardization of histopathology, reexamination of randomly selected cases by another pathologist and reexamination of previously diagnosed cases by the same doctor are periodically performed. For error detection of cytoscreening, cytologists are obligated to reexamine random samples of 1 to 10% of negative gynecological slides. Evaluation of sufficiency of slides as required by the Bethesda System is referred to diagnostic interpretation. PMID- 8350530 TI - [Standardization in hematology and the use of the data in clinical laboratories]. AB - Recently developed automated blood cell counters provide accurate and precise data on complete blood count (CBC). The results of nationwide surveys obtained using them are usually better than those obtained by biochemical tests. The precision of CBC counting has been improved owing to the efforts of laboratories and manufacturers. As for hemoglobinometry, the cyanmethemoglobin and oxyhemoglobin methods used in blood cell counters gave different results for fresh and artificial blood in control surveys. Now instead of the oxyhemoglobin method, the sodium lauryl sulfate-hemoglobin method is used to minimize the variation among different counters. The biggest problem at present is the lack of control blood which can be used for any blood cell counter. Another problem is the laboratory report sent to clinicians, which gives only numerical data. However, other comments and normal reference values should also be presented. Sufficient care may not be taken for normal reference values; they vary considerably among different laboratories. Also, most laboratories and manufacturers now use various conventional units for CBC, but the SI unit should be used for comparison of the data. In conclusion, nationwide unification of CBC values should be established in the near future with cooperative efforts by laboratories and manufacturers. PMID- 8350532 TI - [Problems of survey materials in external quality control survey]. AB - In the past over twenty years the Japan Medical Association Quality Control Survey Committee has experienced various types of problems in preparing a large amount of different control survey materials with some matrix effects. This may have caused inappropriate evaluation for some of the participated laboratory. Not only the participated laboratories but also some industrial companies should participate to identify the exact matrix effects, so that the Committee may be able to avoid some inappropriate decisions on evaluation of the reported results. However, at the present time, no standard is available for the identification of matrix effects. The Japanese Committee for Clinical Laboratory Standards, in 1991, organized the research group on external quality control, and suggested a proposal to identify some matrix effects of survey materials for a particular assay system. PMID- 8350533 TI - [Who manages medical machines and tools in the home? Control of these medical devices is difficult under the cost containment plan of the health insurance system]. AB - In 1978, on the 30th anniversary of WHO, Dr. H. Maller who was the Secretary General said, "Down with HIGH BLOOD PRESSURE" in the elderly social welfare. Since then, many kinds of sphygmomanometers and blood sugar testers have been produced and sold on a commercial basis. However, there is no one controls the quality standards of these devices. Eighty practitioners from all over the country tested the blood pressure of 13,000 patients, using 6 kinds of electric sphygmomanometer, such as MATUSITADENKOU EW-252, MATUSITASANGYOU ZH881-A, OMURON HEM703C, SHARPE NB-650, TERUMO ES-P100 and TAKEDA MEDICAL US-731. Results of the examination were not good. Fifty to 75% of the devices were accurate, but difficult for many patients to use. Data from blood sugar testers, ANTSENSE, GULTEST, GULCO. SYSTEM and GULUCOTEX, were compared. In one test, there was a 110 mg/dl difference between ANTSENSE (it's constantly high) and GULCO. SYSTEM (it's generally low); the difference was 33.7mg/dl on average, but no accidents have happened. Recently, to economize health insurance costs in Japan, the government has cut the fee paid for biochemical devices. As a result, we are concerned that incorrect management of these machines and tools may occur. PMID- 8350534 TI - [A proposal to convert our view from precision into accuracy in routine analysis]. AB - Recently, measurement systems in clinical chemistry have been improved to be more precise in analysis than those in 1980s. As a result, several advances in instruments and reagents have been brought such as incorporating microprocessors into hardwares of instruments and developing ready-to-use reagents, and the precision level of measurement systems is now sufficient for routine analysis. In the near future, however, we will have to focus on the accuracy of measurement systems to obtain accurate and commutable laboratory data. We report a present status of the precision in routine analysis and our activity in data maintenance for accurate analysis by reference methods. PMID- 8350535 TI - [Granule-accumulation in VERO cells used for determination of antitoxin titration by micro cell culture method: II. Nature of granules and influence on the potency testing of diphtheria toxoid]. AB - Accumulation of granules occurs in VERO cells when mouse serum was added in high concentration. The nature of the granule and influence of the granule accumulation on the potency testing of diphtheria antitoxin were studied. The concentration of triglyceride in VERO cells increased 15 folds after 24 hours of incubation by the addition of undiluted mouse serum. Kinetical study of the increase of triglyceride and electron microscope observation suggested that the accumulated granules might be oil droplets with an average diameter of 0.27 micron. The end point reaction of neutralization of diphtheria toxin by the standard antitoxin was analyzed by the addition of mouse serum to the micro cell culture using VERO cells. The mean values of the end point reactions in the cell cultures added with high concentrations of mouse serum were -2.324, -2.338 and 2.346, while that of the control group was -2.343. The variance of these mean values in the experiment and control groups were 0.0017, 0.0024, 0.0017 and 0.0021, respectively. A test of homogeneity of variance for these data showed no significant difference between them. Furthermore, antitoxin titer of the serum specimens of mouse immunized with diphtheria toxoids determined by the micro cell culture method were compared with that obtained by rabbit skin test; a high correlation between the antitoxin titers by the two techniques was recognized. The results were comparable with those of guinea-pig sera. From these results it is evident that little influence, if any, was observed in the potency testing of diphtheria antitoxin using VERO cells, in spite of the remarkable accumulation of granules. PMID- 8350536 TI - Timing is everything: the growing need for emergency nurse practitioners. PMID- 8350537 TI - Cost consciousness and the emergency nurse. PMID- 8350538 TI - Daddy's little girl. PMID- 8350539 TI - More on family presence during resuscitation. PMID- 8350540 TI - Violence in the emergency department: a daily challenge. PMID- 8350541 TI - Introduction of standardized protocols into one pediatric emergency department. PMID- 8350542 TI - Greetings from the "Trauma Center of Somalia". PMID- 8350543 TI - A 31-year-old woman with acute inferior myocardial infarction, cardiac arrest, and subsequent thrombolysis. PMID- 8350544 TI - Diagnosis of ventricular tachycardia: a case presentation. PMID- 8350545 TI - Driving practices, risk-taking motivations, and alcohol use among adolescent drivers: a pilot study. AB - OBJECTIVE: To explore risk-taking motivations, driving practices, and alcohol use in rural adolescent drivers. DESIGN: Descriptive correlational study, that used three self-administered questionnaires: Risk Taking Questionnaire, Driving Practices Questionnaire, and Short Michigan Alcohol Screening Test. METHODS: Test instruments were administered to 23 adolescent drivers, aged 16 to 18 years, recruited by school guidance counselors. RESULTS: Risky driving practices were associated with alcohol use (r = 0.73) and greater risk-taking motivations (r = 0.75). The mean score on the Short Michigan Alcohol Screening Test (4.23) reflected alcoholic tendencies. Male gender was moderately associated with risky driving practice (r = 0.54). CONCLUSION: Drinking alcohol and risky driving may represent a broader risk-taking syndrome. In identifying injury-susceptible individuals, gender may be less useful than identification of driving practices. Injury alone may an indicator of risk-taking behavior, but when injury is combined with alcohol use the index of suspicion increases. Emergency nurses can screen injured adolescents for risk-taking motivations and discuss injury history and perceived injury susceptibility. Awareness is the first step in initiating self-protective measures. PMID- 8350546 TI - Psychosocial support of trauma patients in the emergency department by nurses, as indicated by communication. AB - OBJECTIVE: To test the hypothesis that a difference exists between the perception of the nurse and that of the observer regarding the extent of verbal and nonverbal communication that occurs between nurses and trauma victims (and their families) in the emergency setting. DESIGN AND SETTING: Typical descriptive design study completed in a large metropolitan emergency and trauma center in central Michigan. METHODS: Verbal and nonverbal interaction between nurses and trauma victims and their families were observed by one of two researchers and scored with the Moore-Schwartz Data Collection Tool. The nurses then self reported these same items. RESULTS: Significant differences existed between the researchers' scores and the nurses' self-report scores. This was demonstrated by the Spearman Rank Correlation Coefficient (0.2361, p = 0.05), the Wilcoxon Signed Ranks Test (61.50, p = 0.0004), and the test (-3.35, p = 0.01). The Spearman Rank Correlation Coefficient also demonstrated significant relationships between the nurses' self-report scores and age (0.3716, p = 0.05), gender (-0.360, p = 0.05), and educational level (-0.4209, p = 0.05). No relationship was found between the nurses' self-report scores and the trauma score or age of the patient, or years of emergency department nursing experience. CONCLUSION: Nurses report that they are communicating verbally and nonverbally with trauma victims and their families in the emergency setting, but often were not observed to be doing so. Emergency nurses may not be delivering the holistic care and psychosocial support that they believe they are. PMID- 8350547 TI - Emergency nursing on the Kenyan-Somali border. PMID- 8350548 TI - The forgotten vital sign: temperature patterns and associations in 642 trauma patients at an urban level I trauma center. AB - OBJECTIVES: (1) Identify compliance with the standard of practice that trauma patients have body temperature measurement recorded. (2) Describe the range of temperatures in a sample of trauma patients. (3) Identify associations between temperature and other clinical and trauma variables. DESIGN: Descriptive analysis of a cohort of trauma victims. METHODS: We identified patients with traumatic injuries during a 14-month period with a computer-based trauma registry. Patient charts were reviewed for demographic information, injury data, assessment data, and outcomes. The ED chart, nursing notes, and trauma flow sheets were reviewed in search of a documented temperature assessment. RESULTS: A cohort of 642 trauma patients was identified during the study period. Thirty-two percent were admitted to an ICU; 17% went directly to surgery. The mortality rate was 3.4% (n = 22). Most patients were male (65%), young (mean age, 34 +/- 18 years), and victims of blunt trauma (93%). Seventy-seven percent of patients had a temperature measurement recorded in the emergency department. Patients with minor injuries were more likely to have had their temperature measured (79%) than those with moderate (64%) or severe (64%) injuries (p = 0.0009). Among the 495 patients with recorded temperatures, temperatures ranged from 26.5 degrees to 39 degrees C, with a mean of 36.7 degrees +/- 1.1 degrees C. Ten percent of the patients had temperatures less than 36 degrees C. Temperature correlated negatively with ISS (r = -0.20; p = 0.0001) and positively with RTS (r = 0.37; p < 0.0001). CONCLUSIONS: We conclude that a significant proportion of trauma patients brought to a level I trauma center are hypothermic, with temperatures lower in patients more severely injured and in patients who die. Yet temperature measurement, a simple and standard nursing procedure, is often ignored in trauma resuscitation. PMID- 8350549 TI - Changing from heparin to saline flush solutions: a research utilization model for implementation. PMID- 8350550 TI - Development of a criteria-based performance appraisal for emergency department staff nurses. AB - Developing a criteria-based performance appraisal tool is a rewarding effort, but not one to be taken lightly. It took weeks. At times, the project loomed as "mission impossible." A reflection of its success is the fact that other ED staff members (e.g., charge nurses, clerks, triageurs, and lab assistants) now want criteria-based performance appraisals for their positions. We have just finished a job description and criteria-based appraisal for laboratory assistants. PMID- 8350551 TI - From the emergency department to the telemetry unit: is a registered nurse needed to transport? PMID- 8350552 TI - Evaluation of two reusable wound irrigation systems. PMID- 8350553 TI - Triage form and body charts. PMID- 8350554 TI - A tPA ninety-minute protocol. PMID- 8350555 TI - Triage assessment and nursing record. PMID- 8350556 TI - Massive transfusion protocols. PMID- 8350557 TI - The "discovery doctrine" in nursing malpractice. PMID- 8350559 TI - Weekly educational conferences. PMID- 8350558 TI - Warm-weather injuries. PMID- 8350560 TI - The febrile child in the emergency department. PMID- 8350561 TI - Trauma quality management: closing the loop. PMID- 8350562 TI - A 3-year-old with bradycardia. PMID- 8350564 TI - Code blue perspectives. PMID- 8350563 TI - Emergency nurses' response to Hurricane Andrew's devastation in southern Florida. PMID- 8350565 TI - A tourist's view of emergency care "al' Italia": lessons learned. PMID- 8350566 TI - A look at our new emergency department: Soldiers and Sailors Memorial Hospital, Penn Yan, New York. PMID- 8350567 TI - [In Egypt mothers trust in Daya. Interview by Arja Laiho]. PMID- 8350568 TI - [Dear midwives]. PMID- 8350569 TI - [Teamwork of clients at Lapinlahti maternity counseling center--experiences from the ITU-project]. PMID- 8350570 TI - [Assessment of the current status of maternity care. Interview by Arja Laiho]. PMID- 8350571 TI - [Report of water bubbles relieving pain of women in labor]. PMID- 8350572 TI - [Artificial intraocular lenses in patients with cataracts and glaucoma]. AB - The authors evaluated 52 glaucomatous eyes in which, after the extracapsular cataract extraction, artificial posterior lens has been implanted. In 32 patients glaucoma has been treated for 2-6 years. In 7 patients of this group, it was not possible to control the intraocular pressure before surgery and in these cases simultaneous trabeculectomy, extracapsular cataract extraction and the implantation of artificial posterior lens were performed. In 13 patients, anti glaucomatous surgery had been performed before, and in 7 cases, glaucoma was diagnosed in the preoperative period. We considered our results as satisfactory since in 67% visual acuity was over 0.5; 29% of the patients did not require anti glaucomatous treatment, whereas 71% took anti-glaucomatous drugs in reduced doses. In our opinion, glaucoma is not a contraindication for artificial lens implantation, although surgery can be technically more difficult. PMID- 8350573 TI - [Intraocular lens implantation in the glaucomatous eye]. AB - Cataract extraction with intraocular lens implantation was performed in 32 eyes of 32 patients in the years 1990-1992. Surgery was performed in 10 eyes with well controlled intraocular pressure without any antiglaucomatous operation, in 10 because of inadequate control with simultaneous trabeculectomy, in 7 after earlier filtering procedures and in 5 with secondary glaucoma. Surgical technics, intra- and postoperative complications and the results are discussed. Visual acuity in 18 eyes was 0.5-1.0, in 10 eyes 0.1-0.4 and in 2 it was 0.05. The follow-up for all the eyes yielded normal intraocular pressure, in most cases without additional pharmacological treatment. PMID- 8350574 TI - [Early and late observations of intraocular pressure in patients with implanted intraocular lens]. AB - The aim of the paper was to evaluate intraocular pressure changes that follow the implantation of posterior intraocular lens. In two examined groups of patients (I group--sulcus ciliaris, II group--intracapsular implantation) the decrease of average intraocular pressure values was observed in the early days after surgery, then during 3 months, it gradually returned to the initial values. This decrease was less marked in the first group of patients. Long-term observation showed the stabilization of intraocular pressure at a level similar to the mean values before surgery. PMID- 8350575 TI - [Possible advantages of visual evoked potentials and computerized static perimetry in early diagnosis of glaucoma]. AB - Aim of the studies was to evaluate usefulness of the visual evoked potentials and static perimetry in diagnosis of an early glaucoma. There were 12 examined cases, divided into 3 equal groups: 1) patients suspected for glaucoma basing on the characteristic picture of the optic disc, 2) patients after acute glaucoma in one eye with no history of the disease in the fellow eye, 3) patients with open angle glaucoma diagnosed in one eye. Abnormal results of the examinations were found only in the second group. The authors concluded that visual evoked potentials and static perimetry could be helpful in proper diagnosis of many difficult cases suspected for glaucoma. PMID- 8350576 TI - [Diagnostic and therapeutic problems of juvenile glaucoma]. AB - The material comprised 27 patients, aged 6-15 years, treated for juvenile glaucoma. Non-typical first symptoms, good visual acuity in the majority of the cases, the lack of anatomical changes of anterior segment of the eye and the elongation of the anatomic axis, difficulties in the evaluation of optic disc changes, especially in myopic eyes, and the lack of correlation of these changes with the results of visual field examination, little reliable in children, and also very often the normal intraocular pressure values, delay the diagnosis and make it much more difficult. The repetition of tests and the indication of the C factor make the diagnosis much easier. During the follow-up, intraocular pressure was well-controlled in 87% of the cases, 10% of them with additional optic treatment. PMID- 8350577 TI - [Glaucoma after congenital cataract extraction in children]. AB - The clinical material comprised 45 eyes in 33 children aged from 5 months to 8 years. In the period of 5 days to 7 years after congenital cataract surgery, an increased intraocular pressure has been observed. Antiinflammatory treatment, optic, cyclocryotherapy, synechia-lysis, anterior vitrectomy, YAG-laser and trabeculectomy were applied, depending on the mechanisms that caused the increase of intraocular pressure. In 1-5 years follow-up, the control of intraocular pressure, using the pharmacological treatment and/or surgery, was obtained in 88.4% of the cases. On admission, the enlargement of the eyeball was observed in 26.6% of children, whereas in every fifth of them the cupping of the optic disc was recorded. PMID- 8350578 TI - [Trabeculotomy and goniotomy in congenital glaucoma]. AB - The authors evaluated efficiency of antiglaucomatous surgery in 73 eyes of 50 children, staying under clinical control in the years 1969-1991. It was showed that after trabeculectomy, as the primary procedure, intraocular pressure was normalized much more often (40.9%) than after goniotomy (20.2%). In cases operated many times using different technics, more effective was goniotomy. Better visual acuity was found in cases with intraocular pressure well controlled after one surgical procedure. The most common complications connected with surgery were discussed. PMID- 8350579 TI - Trabeculectomy with 5-fluorouracil in complicated glaucoma. PMID- 8350580 TI - [Laser trabeculoplasty in open-angle glaucoma treatment--long term results of treatment]. AB - The authors present the results of open-angle glaucoma treatment, in the cases where laser trabeculoplasty was the basic treatment. The follow-up of 53 treated patients (72 eyes) was approximately a little more than 3 years. The stabilization of the basic eye functions, i.e. the visual acuity in 76.4% and the visual field in 84.7% of the cases, was obtained. As a result of the treatment, a decrease of intraocular pressure below 21 mm Hg was obtained in 84.7% of the cases whereas the outflow facility factor c > 0.15 was observed in 72.2% of the examined eyes. The low outflow facility factor is one of the causes of the failures. PMID- 8350581 TI - [Surgical treatment of absolute and secondary glaucoma with rubeosis iridis]. AB - An analysis of 52 cases of patients operated with cyclo-diathermy under the scleral flap has been presented. The scleral flap was situated depending on the changes in the angle of the anterior chamber of the eye. The thickness of the prepared flap was 3/4 of thickness of the sclera. The flap was over ciliary body, in one third of the eyeball. Diathermic puncture was performed in 3 rows while perforating puncture, draining off the aqueous humor from the posterior chamber, was performed 2 mm from the limbus. In 45 cases, intraocular pressure was normalized after the first operation, in 4 cases after the second one, whereas in 3 cases the pressure was kept at the level of 30-40 mm Hg. PMID- 8350582 TI - [Microsurgical modification of Allen's glaucoma operation]. AB - The modified anti-glaucomatous operation, introduced its classical version by Allen, has been presented in this paper. The microsurgical version could be defined as micro-cyclodialysis with basal iridectomy, combined with the restoration of the anterior chamber. The surgery was performed in simple glaucoma and glaucoma in aphakic eyes. The details of the surgery and the illustrations of its respective phases have been presented. The results were based on clinical observation of 41 patients. The satisfactory results, up to 6 months, were obtained in 85.3% of the patients. Later the percentage decreases to 78%. For 10 aphakic eyes stabilization was obtained in 9 cases. PMID- 8350583 TI - [Doctor of medicine Maria Stankiewicz-Strozewska (1935-1992). Obituary]. PMID- 8350584 TI - [Preventive antibiotic administration for prevention of nosocomial septicemia in very small premature infants (VLBW infants)--preventive vancomycin administration against infections with coagulase negative streptococci--prevention of translocation with oral cefixime therapy in intestinal colonization with pathogenic gram-negative pathogens]. AB - VLBW-infants below 1500 g of birth weight have a quite high risk to acquire a nosocomial sepsis. 20-40% of all infants exhibit signs of nosocomial infection once during neonatal intensive care. The rate of infection is related to technique and amount of used invasive devices as to gestational age. Coagulase negative staphylococci (CONS) and gram-negative organisms contribute most to these cases of sepsis. In a three phase study we tried to demonstrate the efficacy of different mechanisms to change the rate of nosocomial sepsis. During the first phase a strict hygienical protocol was enforced as isolation, care with sterile gloves and aseptic techniques in introducing and maintaining i.v. lines. In a second phase we started a randomized controlled study of prophylactic vancomycin (10 mg/kg/day in two doses). In a third phase we added an oral antibiotic regime with cefixime for all patients with positive cultures for gramnegative organisms under the hypothesis of translocation from the gut as the way of infection. During the first phase 23.7% of 76 patients enrolled acquired CONS-sepsis, 0.52% gramnegative sepsis. During the second phase (41 patients) 6 patients in the control group acquired CONS-sepsis, none in the vancomycin-group. The rate of gramnegative infections was not different (4 and 3 cases). During the third phase (vancomycin plus cefixime eventually in cases of positive stool cultures) no case of nosocomial sepsis occurred (35 patients, 11 positive cultures). The management used in phase 3 reduced the rate of nosocomial infections in VLBW-infants drastically. PMID- 8350585 TI - [Effect of body position and positioning changes on lung function of ventilated premature and newborn infants]. AB - We studied 21 intubated premature infants (wts 800-2800 g) with respiratory distress syndrome between day 2 and 10 to evaluate the effect of body position on lung mechanics and gas exchange. The dynamic compliance of the total respiratory system was similar in the prone and supine position. When the infant was turned from the supine or the prone position to the other one, a significant improvement of oxygenation was seen temporarily. Positioning did not significantly affect the dynamic compliance, the minute volume or pCO2. In circulatory stable premature infants a change of the body position probably alters the regional ventilation to perfusion ratio and leads to a reduction of intrapulmonary venous admixture. PMID- 8350586 TI - [Which therapy is necessary for prenatally diagnosed multicystic kidney dysplasia?]. AB - Multicystic dysplastic kidneys (MCD) were found in 17 of 114 neonates with prenatal diagnosis of urinary tract malformations. Distribution of side and of sex was not different. Contralateral malformations were present in 3 infants. One of them with contralateral renal dysplasia and cardiac malformation died at the age of 4 weeks. All other children so far have a normal renal function. Three neonates presented with a palpable abdominal mass, 2 infants had urinary infections during the first year of life. Two neonates had obstruction of the contralateral kidney caused by the giant MCD which relieved after nephrectomy. Hypertension or development of malignancy were not noted. Nephrectomy was performed in 10 infants at the mean age of 3.2 months. Six infants had conservative treatment and a complete regression was noted in 5 of them within a period of 8 to 18 months. Prenatal diagnosis of MCD enables early recognition of contralateral urinary malformations and of problems caused by the MCD itself. Conservative treatment is recommended in all asymptomatic patients. Studies of the natural history may show that regression of MCD is the rule and could account for many cases with apparent unilateral renal agenesis. PMID- 8350587 TI - [Protracted croup syndrome. Bacteriologic findings and therapeutic consequences]. AB - BACKGROUND: Croup normally is characterized by acute onset and a self limited course of only few days. In 1990 and 1991 at the University Children's Hospital Freiburg an unexpected high number of patients were hospitalized for prolonged Croup syndrome. Expanded microbiological investigations were used to uncover etiologic factors. METHODS: Of a total of 138 inpatients with Croup 60 (17 in their first year of life, 21 in the second year of life and 22 infants older than 2 years) had bacteriological (37 nasopharyngeal-, 4 tracheal-aspirates or 19 throat swabs), and virological (antigen detection in nasopharyngeal aspirates, n = 28) tests. Of these patients 48% were hospitalized longer than 3 days (mean 4,7; range 1-18 days). RESULTS: Bacteria found: B. catarrhalis 24/11 (total/pure culture), S. pneumoniae 15/6, H. influenzae 10/3, S. group A 5/4 and S. aureus 4/1. Sixteen specimen yielded more than one pathogen, one specimen was sterile. Nasopharyngeal secretions had the most reliable results: Pure cultures (72%) and associations of two pathogens (87%) were found in these aspirates, and only 26% of the unspecific mixed findings (p < 0.005; chi 2-Test). Of the patients hospitalized longer than 3 days 27.6% had positive cultures for H. influenzae, whereas only 6.5% of those hospitalized shorter (p < 0.05; chi 2-Test). The only microorganism with an age-bound distribution was B. catarrhalis found predominantly (54.2%) in the 2nd year of life, with 62% of patients positive (p < 0.05; chi 2-Test). Virus found: RSV (n = 3), Parainfluenza 2 (1) and Parainfluenza 3 (1). CONCLUSIONS: Nasopharyngeal aspirate is the most reliable specimen for a bacteriologic diagnosis in Croup. In the second year of life B. catarrhalis is present in most Croup cases, and H. influenzae was associated with a prolonged course of the disease. An appropriate antibiotic therapy therefore must cover these two pathogens. PMID- 8350588 TI - [Sedation versus general anesthesia in pediatric endoscopy]. AB - Upper endoscopy was performed in 567 patients: 237 under general anesthesia, 261 in intravenous sedation with midazolam and etomidat (mean dosage 0.26 mg/kg bodyweight), 69 without any premedication. In these many patients defended strongly and some investigations have to been interrupted. On the other hand general anaesthesia needed much more time and personnel and produced more costs. In our experience sedation with midazolam and etomidat is most comfortable for patient and endoscopist and the time needed is shorter than in general anaesthesia. Therefore we recommend this method even in therapeutic endoscopy, except only in sclerotherapy of esophageal varices. PMID- 8350589 TI - Constitutional interstitial deletion of 17(p11.2) (Smith-Magenis syndrome): a clinically recognizable microdeletion syndrome. Report of two cases and review of the literature. AB - We present two patients, a 12 year old Turkish and a 7 year old Italian girl, with severe mental retardation, multiple congenital malformations and a constitutional interstitial deletion of the short arm of chromosome 17, del(17) (11.2). The main clinical features of this syndrome which is also referred to as the Smith-Magenis syndrome consist of a broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, hoarse deep voice and peripheral neuropathy. Behavioural abnormalities include hypermotility, self mutilation and sleep disturbances. The remarkable consistency of the main clinical features of the 59 patients documented so far permits the clinical diagnosis of this syndrome; a fact which is of importance, since many of the reported patients- including ours--were considered normal on earlier cytogenetic studies. PMID- 8350590 TI - [Echocardiographic diagnosis of congenital diverticuli of the right and left ventricle]. AB - A congenital diverticulum of the ventricle is a very rare cardiac lesion which is almost always associated with additional cardiovascular anomalies. In the majority of cases a diverticulum of the heart has been diagnosed during cardiac catheterization for evaluation of additional cardiovascular anomalies. We report noninvasive echocardiographic diagnosis of a congenital cardiac diverticulum in two patients. Noninvasive imaging of the diverticulum facilities planning of cardiac catheterization, angiographic imaging and surgical treatment of this rare anomaly. PMID- 8350591 TI - Respiration and heart rate variation in normal infants during quiet sleep in the first year of life. AB - Forty-three all-night sleep recordings have been performed on 19 control infants of the ages 6 weeks, 6 months and 1 year. During eight hour periods 22 physiological parameters were sampled by a personal computer based monitoring system and stored on an optical disk. This paper reports on spectral analysis of breathing and heart rate patterns during the first and last episode of quiet sleep at three different age groups. The results demonstrate that the respiratory rate during quiet sleep decreases (6 weeks: 37.2 +/- 5.4; 6 months: 30.1 +/- 4.9; 1 year: 24.1 +/- 1.8; adults (mean age 25.1 +/- 2.8 years; n = 10): 14.8 +/- 1.8; values are means +/- one standard deviation in breaths/min) and the respiratory coefficient Pm/Ps (higher values of Pm/Ps indicate lower respiratory variability) increases with age (6 weeks: 2.3 +/- 0.7; 6 months: 3.2 +/- 1.1; 1 year: 3.4 +/- 1.0; adults: 4.5 +/- 1.0). The calculation of the heart rate in beats per minute (bpm) and heart rate variability (%) revealed the following results: 6 weeks: 127.4 +/- 11.5 bpm, 3.8 +/- 1.5%; 6 months: 119.4 +/- 17.3 bpm, 4.2 +/- 1.7%; 1 year: 110.3 +/- 21.5 bpm, 5.8 +/- 2.3%; adults: 59.2 +/- 8.5 bpm, 4.3 +/- 2.2%. A comparison of the cardiorespiratory data from the first and last quiet sleep period showed no significant differences within either age group. PMID- 8350592 TI - [Variability of corticosterone methyl oxidase (type II) deficiency. Presentation of three case reports]. AB - We report on three cases of Corticosterone Methyl Oxidase Typ II deficiency in two siblings and one boy. All three children were presented with typical symptoms of a saltlosing syndrome (vomiting, poor drinking, weight loss, hypotonia). Hyponatremia and hyperkalemia, low plasma aldosterone concentrations when related to high plasma-renin-activities suggested deficiency in the final steps of aldosterone biosynthesis. Variable degrees of enzyme deficiency and no relation of biochemical findings to the clinical symptoms were observed. Clinical symptoms became less severe with age. Diagnosis of CMO II-deficiency was established by an abnormal high ratio of 18-hydroxycorticosterone to aldosterone, by measurement of their precursors and metabolites in plasma and urine. In one sibling negative values may have been caused by suppression of the renin-angiotensin-system due to high sodium replacement therapy. PMID- 8350593 TI - [Holt-Oram syndrome in combination with reciprocal translocation, lung hypoplasia and cardiomyopathy]. AB - A now two years old girl had developed respiratory insufficiency shortly after birth requiring prolonged artificial ventilation. A hypo- and dysplasia of the right lung was identified as the underlying cause. Further diagnostic evaluation revealed a malformation of bones, i.e. shortness of the humerus, aplasia of the radius, shortness of the ulna and a congenital anlage of four metacarpal bones in fixed malposition. In addition, an atrial septal defect of the sinus venous type with left-to-right shunting was present. This, in combination with the sceletal abnormalities pointed to the diagnosis of Holt-Oram syndrome. In her first year of life the patient also developed a hypertrophic non-obstructive cardiomyopathy. Cytogenetic analysis of her family revealed a reciporke translocation between chromosome 1 and 11 (t -1, -11 (1p13, 11q13)) in the patient herself, her father and the father and a sister of her father. However, this finding as well as the hypertrophic cardiomyopathy has to be regarded as being independent from Holt Oram syndrome. PMID- 8350594 TI - [Persistent pulmonary hypertension in the newborn infant caused by aneurysm of the vein of Galen]. AB - A male full-term neonate is described in whom cardiac insufficiency developed within 24 hours post partum. Ultrasound revealed an arterio-venous fistula of the vein of Galen. The patient's condition did not allow surgical correction and he died on the 22nd day of life. Persistent pulmonary hypertension was an important accompanying feature. The literature is reviewed with respect to the prognosis and the up to now seldom reported complication of persistent pulmonary hypertension of the newborn (PPHN). PMID- 8350595 TI - Cell-cell and cell-matrix interactions in the skin. PMID- 8350596 TI - Cellular selection in the genesis of multicellular organization. PMID- 8350597 TI - Undifferentiated keratinocytes control growth, morphology, and antigen expression of normal melanocytes through cell-cell contact. AB - BACKGROUND: Melanocytes in the normal human epidermis are generally dendritic and neither proliferate nor express melanoma-associated antigens. In culture, on the other hand, melanocytes are bi- to tripolar, proliferate with 2 to 4 day doubling times, and express melanoma-associated antigens. This observation prompted us to investigate the regulatory role of keratinocytes for growth, morphology, and antigen expression of melanocytes. EXPERIMENTAL DESIGN: Melanocytes and keratinocytes were cultured under three different co-culture conditions: (a) separated by a semiporous membrane, (b) in monolayer cultures allowing direct contact between cells, and (c) in three-dimensional epidermal reconstructs. RESULTS: Melanocytes separated from keratinocytes by semiporous membranes remained di- and tripolar and could not proliferate in medium optimal for keratinocytes. When cell-cell contact was established between melanocytes and undifferentiated, but not differentiated, keratinocytes, melanocytes proliferated at a rate similar to keratinocytes and they developed multiple dendrites. In co cultures allowing the multi-layered growth of keratinocytes, melanocytes were nonproliferative when juxtaposed to undifferentiated keratinocytes in the basal layer, but proliferated when surrounded by differentiated keratinocytes in the intermediate and upper layers. Expression of melanoma-associated antigens on melanocytes decreased to similar levels as in normal skin when melanocytes were in direct contact with undifferentiated, but not differentiated, keratinocytes. CONCLUSIONS: Undifferentiated, but not differentiated, keratinocytes control growth, morphology, and antigen expression of melanocytes through direct cell cell contact. These results suggest that the phenotypic characteristics of nevus and melanoma cells in the dermis, i.e., proliferation and expression of tumor associated antigens, may be due to their loss of contact with undifferentiation keratinocytes. PMID- 8350598 TI - A potential role for N-cadherin in mediating endothelial cell-smooth muscle cell interactions in the rat vasculature. AB - BACKGROUND: The cadherins are a family of calcium-dependent cell adhesion molecules that play a critical role in morphogenetic cell interactions in the embryo. N-cadherin has been identified in neural and non-neural tissues, including developing muscle; however, there are few reports of N-cadherin expression in adult mammals. We attempted to identify N-cadherin in the rat vasculature and to ask whether it has a role in mediating vascular cell interactions. EXPERIMENTAL DESIGN: Vascular tissues were isolated from Fischer rats and analyzed immunohistochemically and by Western blotting using pan cadherin and N-cadherin antibodies. Anti-N-cadherin antibodies were used in an in vitro cell adhesion assay to determine if N-cadherin mediates interactions between smooth muscle cells (SMC) and endothelial cells (EC). RESULTS: Western blot analysis of vascular tissues reveals a 135 kilodalton (kd) band that is recognized by anti-N-cadherin antibodies. N-cadherin localizes in the rat aorta to the endothelium and to the smooth muscle cell layer beneath the internal elastic membrane. A cell adhesion assay demonstrates that rat SMCs and ECs adhere to each other in a Ca(2+)-dependent manner, and an anti-N-cadherin antibody inhibits approximately 25% of this adhesion. CONCLUSIONS: Our data indicate that N-cadherin is expressed in large vessels of the rat and is capable of mediating EC-SMC adhesion in vitro. It is noteworthy that N-cadherin localizes to a population of SMCs in the rat aorta adjacent to ECs suggesting that N-cadherin may mediate EC-SMC interactions in vivo. PMID- 8350599 TI - Clinicopathologic study of dextran sulfate sodium experimental murine colitis. AB - BACKGROUND: We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. EXPERIMENTAL DESIGN: Acute colitis was induced in Swiss Webster mice by 7 days of oral DSS with animals sacrificed daily. Chronic colitis was induced by: (a) 7 days of oral DSS followed by 7 days of H2O (for 1, 2, and 3 cycles) and (b) 7 days of oral DSS followed by 14 and 21 days of H2O. In each experimental group, the entire colons were examined histologically and correlated with clinical symptoms. RESULTS: Acute clinical symptoms (diarrhea and/or grossly bloody stool) were associated with the presence of erosions and inflammation. More importantly, the earliest histologic changes which predated clinical colitis was loss of the basal one-third of the crypt (day 3), which progressed with time to loss of the entire crypt resulting in erosions on day 5. The earliest changes were very focal and not associated with inflammation. Inflammation was a secondary phenomena and only became significant after erosions appeared. Animals treated with only 7 days of DSS followed by 14 and 21 days of H2O developed a chronic colitis with the following histologic features: areas of activity (erosions and inflammation), inactivity, crypt distortion, florid epithelial proliferation and possible dysplasia. These changes were similar to animals given 3 cycles of DSS. The clinical disease activity index correlated significantly with pathologic changes in both the acute and chronic phases of the disease. CONCLUSIONS: The mechanism of DSS colitis is presently unknown. However, the finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena. This may be a good model to study how early mucosal changes lead to inflammation and the biology of the colonic enterocyte. Chronic colitis induced after only 7 days of DSS may serve as a useful model to study the effects of pharmacologic agents in human inflammatory disease and mechanisms of perpetuation of inflammation. Finally, we believe that this model has the potential to study the dysplasia cancer sequence in inflammatory disease. PMID- 8350600 TI - Origin of urinary fibronectin. AB - BACKGROUND: Fibronectin (FN) is a major component of the glomerular extracellular matrix and it is also abundant in plasma. In physiologic conditions, FN fragments are excreted into urine. Increased urinary FN excretion has been observed in renal diseases raising the question whether urinary FN could reflect changes in the renal extracellular matrix. This study examines whether urinary FN is filtered from plasma or derived from the kidney and it attempts to specify the potential renal source of urinary FN. EXPERIMENTAL DESIGN: (a) To investigate whether urinary FN is filtered from plasma, labeled, biotinylated FN (b-FN) was injected into rats and urine samples were specifically analyzed for b-FN by an immunoblot procedure. (b) To specify the renal source of urinary FN and to evaluate possible alterations of this protein during passage into final urine, tubular fluid was collected from distinct localizations of the nephron by micropuncture techniques. The samples were analyzed for endogenous FN by a highly sensitive immunoblot system, and the pattern was compared with that normally found in final urine. RESULTS: (a) Urine samples collected over a period of 5 days after injection of b-FN contained no labeled FN. Control experiments in rats with highly elevated glomerular permeability confirmed that the plasma levels of injected b-FN were sufficiently high since b-FN was detected in urine in this condition. (b) The FN fragment pattern, with two protein bands at 75 and 45 kilodaltons, that is normally found in final urine, was already present in samples taken from the early proximal tubule and the distal tubule. CONCLUSIONS: The fibronectin fragments normally found in urine originate from the kidney and are not derived from plasma. Since these fragments are already observed in early proximal tubular fluid, the glomerulus is the probable source of urinary FN. The FN fragment pattern of early proximal tubular fluid is not substantially altered during passage into final urine, thus reflecting glomerular FN release in urine. It is suggested that examination of urinary FN excretion could be helpful in the assessment of altered glomerular extracellular matrix in pathologic conditions. PMID- 8350601 TI - Contemporary perspectives on sport psychology. PMID- 8350602 TI - Blood lactate accumulation in top level swimmers following competition. AB - The purposes of this study were to evaluate the significance of blood lactate values after competitions and the blood lactate-swimming speed relationship to swimming performances. Auricular blood samples (N = 421) were collected in 203 top level Italian swimmers (116 males and 87 females) at the end of competitions performed in a 25 m swimming pool. The distribution of all lactate values differed between males and females. The lowest lactate values occurred in swimmers performing the longest distances both in males (1500 m) and females (800 m). In swimmers performing freestyle events a relationship between V-4 mM (swimming speed at 4 mmol/l blood lactate value) and competition velocities was observed, in males, at 200, 400 and 1500 m and, in females, at 400 and 800 m. The predicted velocity corresponding to the competition lactate value assessed by the individual blood lactate-swimming speed relationship was found to be highly related to the actual competition velocity. Results suggest that blood lactate values in swimmers are a useful indication of individual aptitudes. PMID- 8350603 TI - Changes in physical fitness profile in female basketball players during the competitive season including explosive type strength training. AB - Ten female basketball players served as subjects in order to examine changes in a physical fitness profile during a 22-week official competitive season. Specific explosive type strength training (1-2 sessions per week) was utilized throughout the season. The present findings showed that the entire competitive season led to no systematic changes in the maximum oxygen uptake (from 48.0 +/- 6.6 to 47.0 +/- 6.0 ml.kg-1.min-1), in anthropometric characteristics or in maximal isometric force of the leg extensor muscles (from 2567 +/- 490 to 2622 +/- 747 N). However, significant (p < 0.05) increases occurred during the season both in the average power output during the first 15 s work in an anaerobic jumping test and in the maximal vertical jumping heights in the squat jump (from 21.7 +/- 2.3 to 24.2 +/- 2.4 cm) and in the counter movement jump (from 24.9 +/- 2.6 to 26.3 +/- 2.9 cm). A considerable change occurred also in the shape of the isometric force-time curve of the leg extensor muscles so that the times to produce submaximal force level shortened (p < 0.05). The individual changes during the competitive season both in the power output and in the times of rapid force production correlated negatively (p < 0.05) with the individual initial values recorded before the season. The present findings suggest that the prolonged competitive season in the present female basketball players seemingly placed sufficient demands on the athletes in energy production through aerobic processes to maintain their level of VO2max.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350604 TI - Effect of water temperature on performance, lactate production and heart rate at swimming of maximal and submaximal intensity. AB - The effect of water temperature on performance effort, monitored heart rate and lactate production during freestyle swimming at maximal and submaximal speed has been studied. Fifteen male sprint swimmers performing 100 m swimming and fifteen comparable endurance competitors performing 30 min swimming at submaximal speed served as subjects. Water temperature in separate events was 20, 26 and 32 degrees C. At maximal performance there was a direct relationship between any two of the following parameters: water temperature, average swimming speed, heart rate during the competition and plasma lactate concentration after the event. Thus, the best effort (speed 1.704 m/s), the highest peak heart rate (185 beats/min) and the highest lactate level (19.8 mmol/l) were observed at 32 degrees C (all mean values). In contrast, these values were markedly lower at 20 degrees C. At the submaximal effort, water temperature was related to peak heart rate only. The highest peak heart rate (144 beats/min) was again obtained at 32 degrees C, while the lactate concentration (4.2-5.2 mmol/l) was independent of temperature. Water temperature appears to have a direct effect on performance effort, heart rate and lactate production during swimming at maximal intensity, whereas this effect seems to fade at submaximal efforts. PMID- 8350605 TI - Predictions of maximum oxygen uptake from treadmill walking and running. AB - The purpose of this study was to determine if maximal oxygen uptake (VO2 max) could be accurately predicted with the Astrand-Ryhming (AR) method in conjunction with equations reported by the American College of Sports Medicine (ACSM) that estimate the oxygen cost of submaximal walking and running. Fifty-three subjects (28 males and 25 females) performed three treadmill tests to determine VO2 max and heart rate and oxygen costs of submaximal walking and running. The results indicated that when ACSM estimates of the oxygen cost of walking and running were used with the AR method, reasonably accurate predictions of VO2 max were obtained for the present group of subjects. Correlations between actual and predicted VO2 max values of r = 0.82 and r = 0.86 and standard errors of estimate 0.47 and 0.53 L.min-1 were determined for treadmill walking and running, respectively. These errors are similar to others reported using the AR method with different exercise modes. PMID- 8350606 TI - Cardiorespiratory response to walking in trained and sedentary pregnant women. AB - In order to test whether trained (n = 10) and sedentary (n = 29) pregnant women have different responses to weight-bearing exercise in the second trimester (range 23 to 28 weeks of gestation), subjects walked continuously on a treadmill for 26 minutes: at low intensity for 10 minutes, then an intermediate stage, followed by moderate intensity for 10 minutes. In the trained group, the mean heart rate was lower (p < 0.02) with both low [104.0 +/- 4.5 (SD) versus 117.4 +/ 2.3 bpm] and moderate intensity exercise (128.4 +/- 5.7 versus 145.2 +/- 2.9 bpm) and the associated mean stroke volume was higher (105 +/- 16 versus 84 +/- 17 ml; 103 +/- 15 versus 86 +/- 18 ml, respectively) (p < 0.02). The mean cardiac output, blood pressure and oxygen consumption were the same in the two groups (p > 0.02) at the same absolute workloads. The potential implications of these findings for exercise prescriptions for pregnant women, research evaluation and exercise testing are discussed. PMID- 8350607 TI - Spectral analysis of heart rate variability in athletes. AB - The objectives of the study were to characterize power spectrum pattern of the heart rate variability and assessment of the relative contributions of sympathetic and parasympathetic cardiac nervous system control in athletes. Thirty-three male athletes, swimming (1), canoeing (10), cycling (6), athletics (4), football (3), roller-skating (2) and volleyball (7) aged 23.4 +/- 5.5 years, with a mean athletic level of 18 hours/week (8-45) and 33 sedentary healthy control subjects were included. Ecg signals were recorded after a period of 15 minutes in supine rest with controlled breathing at 15 cycles/min. Signal acquisition was done at 300 samples/sec. From 512 consecutive heart beats, we calculated mean average, standard deviation, maximum and minimum R-R intervals and, after computing the fast Fourier transform, total spectrum power, low frequency (LF), high frequency (HF) components and its ratio (LF/HF). The average R-R interval was 987.7 +/- 168.8 ms and 762.7 +/- 125.3 ms, the variance was 5.44 and 2.51 ms2 and ratio of R-R interval maximum/minimum (E/I ratio) 1.53 +/- 0.16 and 1.41 +/- 0.16, respectively for athletes and control group. Differences between groups were significant (p < 0.01) for all parameters, with higher variability in the athletes. Both spectral bands (LF and HF) had higher power in athletes (LF = 925 +/- 920 and HF = 2258 +/- 2349 ms2) than in the control group (LF = 442 +/- 446 and HF = 1179 +/- 1542 ms2) (p < 0.01). There were no significant differences for LF/HF ratio, or normalized LF (LF%) or normalized HF (HF%) between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350608 TI - The effects of a walking program on body composition and serum lipids and lipoproteins in overweight women. AB - Few prospective studies have been conducted with women to examine the effects of walking on body composition and serum lipid profiles. Overweight women were randomly assigned to either an exercise EX (no. 18) or a nonexercise NEX (no. 18) group. The EX group participated in five 45 min sessions/week of brisk walking at 62 +/- 2% VO2max for 15 weeks. Statistical analysis (2 x 3 repeated measures ANOVA) revealed that the pattern of change in total body weight [F(2.68) = 6.65, p = 0.002] but not body fat percentage, was significantly different between EX and NEX groups; NEX subjects had a 1.6 +/- 0.5 kg gain in contrast to no change in EX subjects. The pattern of change in serum triglycerides, total cholesterol, and LDL-C was not significantly different between groups. The interaction statistic for HDL-C, however, was significant [Pillais Trace (2.33) = 3.73, p = 0.035] with HDL-C tending to rise in the NEX group in contrast to a small decrease in the EX group. Change in kilocalorie intake was positively correlated with change in HDL-C, total cholesterol, and body weight. Change in body weight also correlated positively with change in HDL-C. Our findings suggest that moderate exercise training alone may not be a sufficient stimulus to affect body composition and serum lipid profiles favorably in overweight women. PMID- 8350609 TI - Effect of a protein-sparing diet on responses to exercise in obese subjects. AB - We have studied muscular work efficiency and VO2 peak in seven obese individuals (body mass index: 38.9 +/- 5.8 kg.m-2) before and after twelve days of a low caloric diet (protein-sparing modified fast) providing about 2460 kJ/day. Respiratory gas exchanges were measured at rest and during an exercise protocol through a rubber mask connected to a pneumotachograph and a mass spectrometer. A significant reduction in body mass was observed with the diet therapy (109 +/- 12 vs 105 +/- 14 kg; p < 0.02). No significant differences were observed in VO2 peak (1.78 +/- 0.32 vs 1.88 +/- 0.43 l/min, p > 0.05) and work efficiency (26 +/- 5 vs 24 +/- 4%, p > 0.05), after the diet protocol. It is concluded that the low caloric diet used had no effect on muscular work efficiency. PMID- 8350610 TI - Somatotype of Italian rugby players. AB - Our aim was to collect lacking first-hand data on Italian rugby players. The Heath/Carter anthropometric somatotype method was applied to 28 "A" League performers (RP) aged 25 +/- 3.9 years of age. Their somatotypes and dimensions were compared with those found in previous studies on athletes involved in the same sporting activity, with data collected on 25 "sedentary" young Italians, and with Bailey et al.'s study on Canadians (1982). On average, the RP group resulted as being endomorphic mesomorphs (3.1 +/- 1.1 - 5.6 +/- 1.3 - 1.4 +/- 1.1), a result that is congruent with international data. They differed significantly from the balanced mesomorph CG (2.3 +/- 1.0 - 4.5 +/- 1.2 - 2.5 +/- 1.4) for all the measurements taken, apart from bi-epycondylar width. The peculiar somatotype scores found are congruent with the needs of rugby, an aerobic-anaerobic discipline which requires performers with great muscular power associated with a capacity to furnish energy, mainly through the anaerobic metabolism. PMID- 8350611 TI - Triathlon competition induced a transient immunosuppressive change in the peripheral blood of athletes. AB - This study was designed to determine whether or not physical and psychological stress of triathlon competition causes an immunosuppressive change in the peripheral blood of athletes, if it does occur, how long does it take to recover. Fifteen healthy men, aged 19 to 40, volunteered for this study. Peripheral blood was drawn four times at approximately the same time on the following days; one day before the race, immediately after, one day and eight days after, and served for determining circulating leucocyte and lymphocyte subset counts, in vitro lymphocyte proliferative response and natural killer activity. The results showed that triathlon competition caused considerable changes in the cell counts of peripheral blood leucocyte and lymphocyte subsets, and a transient reduction in vitro lymphocyte proliferative response and natural killer activity, all of which returned to pre-race levels in one to eight days after the race. PMID- 8350612 TI - No effect of endurance exercise on serum bilirubin in healthy athletes and with congenital hyperbilirubinemia (Gilbert's syndrome). AB - Twenty male athletes, mean age 26 years, were studied by a work load test with cycle-ergometer, with increasing power output for 60 minutes until an intensity corresponding to 70% of the individual maximal heart rate was achieved. Ten of them had familial hyperbilirubinemia (Gilbert's syndrome) and ten had been considered as healthy controls. The diagnosis of Gilbert's syndrome was made using the following criteria: unconjugated hyperbilirubinemia, no systemic symptoms, no overt or clinically recognizable haemolysis, normal liver function tests. Blood levels of free fatty acids (FFA) showed a progressive significant increase after muscular exercise in both healthy and Gilbert's syndrome subjects (p < 0.001). The increase was more evident in controls compared to Gilbert's syndrome subjects (p < 0.05). Total and fractionated bilirubin showed no change in both groups. In conclusion, a competitive mechanism between bilirubin and FFA is probably responsible for the lower increase in plasma FFA in Gilbert's syndrome. PMID- 8350613 TI - The stages of exercise behavior. AB - The stages of change model has shown promise in advancing knowledge about smoking behavior change and other negative addictive behaviors. The model was applied to the study of exercise, a healthy rather than unhealthy behavior. A stages of exercise behavior questionnaire was administered to a sample of 235 employees. Next, the ability of a second questionnaire measuring physical activity behavior to differentiate employees according to stage of exercise was tested. Results revealed that 51% of employees were participating in no physical activity (Precontemplation, Contemplatation) and 49% were participating in occasional or regular physical activity (Preparation, Action, Maintenance). Scores on physical activity behavior items significantly differentiated employees among the stages. This model developed on smoking and other behaviors can be generalized to exercise behavior. Understanding the stages of exercise behavior could yield important information for enhancing rates of participation in physical activity. PMID- 8350614 TI - Interleukin-4 and its receptor; modulating effects on immature and mature hematopoietic cells. PMID- 8350615 TI - Retinoid acid supports granulocytic but not erythroid differentiation of myeloid progenitors in normal bone marrow cells. AB - In the new context of the use of retinoic acid (RA) therapy as an inducer of leukemic differentiation and a selective inhibitor of human myeloid leukemia cell growth, we undertook to explore the potential physiological role of retinoids on the proliferation and differentiation of normal bone marrow myeloid progenitors. The effects of continuous exposure of all-trans-RA, its naturally occurring isomer, 13-cis-RA, and its metabolite 4-oxo-all-trans-RA were studied on the growth of normal human bone marrow cells in soft agar, directly and after liquid culture. Retinoids enhanced the total number of granulocytic colony and macrocluster formation in the presence of exogenous colony-stimulating factor (n = 9). Dose-response curve were bell-shaped, with a maximal increment between concentration of 0.5 and 0.05 nM. In all cases, a concomitant decrease of macrophagic colonies was noted. The positive effect on granulocytic colony formation was observed with each of the retinoids tested (all-trans, 13-cis and 4 oxo-all-trans) (n = 5). On erythroid colony formation, all-trans-RA had the opposite effect. Constant suppression of CFU-E and BFU-E colony formation and coloring was observed in a dose-related fashion from 0.1 to 10 microM (n = 5). Thus, in granulocytic, as in erythroid colony formation, retinoids affected both proliferation and differentiation parameters. However, after short-term suspension culture in the presence of all-trans-RA, an increase of both CFU-GM and BFU-E colonies, was observed. These results suggest a specific effect of retinoids on late myeloid precursors and places retinoids as possible candidates for enhancement of normal granulocytic differentiation. PMID- 8350617 TI - Detection of P210bcr-abl in mature granulocytes from Ph1-positive chronic myelogenous leukemia patients by an immunoblotting method. AB - Previously, p210bcr-abl has been detected in Philadelphia-chromosome-positive chronic myelogenous leukemia (CML) blast crisis and established cells originating from blasts. It has not been detected in mature granulocytes in the chronic phase. Protein degradation tends to occur during protein extraction, due to the activities of protease and phosphatase within these cells. Protein was, therefore, extracted in a cell lysis buffer containing alpha 1-antitrypsin and a high concentration of Na3VO4 as inhibitors. In mature granulocytes in the chronic phase, p210bcr-abl was detected and the level of tyrosine phosphorylation estimated by immunoblotting, using the enzyme-labeled antibody method with anti-c abl and anti-phosphotyrosine antibodies. p210bcr-abl was phosphorylated on tyrosine residues in blast crisis cells and K562 cells derived from CML blast crisis, whereas it was dephosphorylated in mature granulocytes from chronic phase CML patients. This suggests that p210bcr-abl in mature granulocytes has no tyrosine kinase activity, or it is extremely weak, and dephosphorylation of p210bcr-abl is associated with differential maturation of immature cells in the chronic phase of CML. PMID- 8350616 TI - Further evidence for the existence of a clonal Ph-negative stage in some cases of Ph-positive chronic myelocytic leukemia. AB - The Ph chromosome abnormality is involved in the pathogenesis of almost all patients with chronic myelocytic leukemia (CML). Previous studies on the B lymphoid cell lineage in two patients with Ph-positive CML suggest that there may also be a clonal Ph-negative stage in CML and that the Ph-positive stage arises by subclonal expansion. To determine whether this is a frequent or a rare occurrence, 14 additional glucose-6-phosphate dehydrogenase (G6PD)-heterozygous patients with CML were studied. In five of these patients there was a statistically significant excess of Ph-negative B-lymphoid cell lines expressing the same G6PD type expressed in the corresponding CML clone. In no case was an excess of B-lymphoid lines expressing the opposite G6PD type recovered. These data provide further evidence that in some patients the Ph chromosome arises in a pluripotent stem cell from a pre-existing Ph-negative clone that enjoys a growth advantage. PMID- 8350618 TI - Human acute myeloid leukaemia cells express adhesion proteins and bind to bone marrow fibroblast monolayers and extracellular matrix proteins. AB - Adhesion protein expression by acute myeloid leukaemia (AML) cells may affect bone marrow stromal localization and determine exposure of leukaemic cells to stromal derived myeloid growth factors. We have analysed the surface expression by myeloid leukaemic cells of proteins with known adhesive function and the ability of AML cells to adhere to bone marrow fibroblasts and the extracellular matrix proteins fibronectin and laminin. Cells from all six patients tested adhered to bone marrow fibroblast monolayers (mean binding 28.8 +/- 12.8%) and to purified fibronectin in five cases studied (mean binding 33.8 +/- 15.3%). Cells from four patients with AML also adhered to laminin (mean binding 20.9 +/- 4.0%). AML cells from the majority of patients with leukaemia at diagnosis or relapse expressed the ligand pair LFA-1 and ICAM-1, the CD2 ligand LFA-3, alpha and beta chains of the integrins VLA-4, VLA-5 and VLA-6, and the hyaluronate receptor CD44. Antibodies to CD11a, CD18, VLA-4 alpha, and VLA-5 alpha failed to inhibit binding of AML cells to bone marrow fibroblasts but anti-VLA-5 alpha antibodies inhibited AML cell binding to fibronectin by approximately 50%. The ability of AML cells to adhere to bone marrow fibroblasts and extracellular matrix proteins such as fibronectin and laminin may to help explain the capacity of AML cells to persist in the marrow during periods of apparent complete remission and to subsequently proliferate under the influence of locally secreted myeloid growth factors. PMID- 8350619 TI - SIL-TAL1 deletion in T-cell acute lymphoblastic leukemia. AB - The TAL1 gene on chromosome 1 encodes a hematopoietic transcription factor. Disruption of TAL1 via chromosomal translocation or a site-specific deletion has been reported in up to 30% of T-cell acute lymphoblastic leukemias (T-ALL). Here we used a polymerase chain reaction (PCR) assay to identify the 90 kb SIL-TAL1 deletion in a group of 19 cutaneous T-cell lymphomas and a series of 142 T-ALL patients (76 children, 66 adults). While none of the T-cell lymphoma exhibited a SIL-TAL1 recombination, seven T-ALL cases showed a type d1 and two patients a type d2 deletion. Of pediatric T-ALL, 9% (7/76) and of adult patients only 3% (2/66) were characterized by this genomic lesion. The deletion correlated with commitment to the T-cell receptor (TCR) alpha beta lineage, but lacked association with a distinct maturation stage. Sequence analysis of SIL-TAL1 breakpoints revealed marked heterogeneity at the junctional region among the nine patients due to random deletion and insertion of N-region nucleotides or templated P-nucleotide addition mediated via illegitimate V(D)J recombinase action. Clonospecific oligomer probes in conjunction with PCR allowed the detection of minimal residual disease in one out of four patients monitored during complete hematologic remission. PMID- 8350620 TI - Constitutive expression of GM-CSF mRNA by CML blast cells is correlated with endogenous megakaryocytic colony formation. AB - Purified blast cells from peripheral blood of 12 patients, with chronic myelogenous leukemia (CML) in chronic phase, were analyzed for the constitutive expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) transcript. Seven out 12 patients exhibited the specific 1.0 kb GM-CSF mRNA. Six from these patients presented an increased level of spontaneous megakaryocytic colony formation. Using an immunocytochemical procedure, the presence of GM-CSF was detected in a large proportion (52% to 72%) of the blast cells of the three patients studied, who were selected for the high expression of GM-CSF mRNA transcripts. Because the role of GM-CSF in the regulation of human megakaryocytopoiesis is well documented, we investigated the inhibiting effect of anti-GM-CSF antibodies on the spontaneous megakaryocytic colony growth of three of the patients expressing the GM-CSF transcript. Addition of anti-GM-CSF had a high neutralizing effect ranging from 60% to 70% inhibition of endogenous megakaryocytic colony growth. As the GM-CSF synthesis by leukemic cells is often induced by interleukin-1 (IL-1), we also investigated the effect of anti-IL-1 antibody on the spontaneous megakaryocytic colony growth of the same three patients. No significant inhibiting effect was observed, showing that the role of GM-CSF in the spontaneous colony formation is not mediated by IL-1. In addition, patients who constitutively expressed the GM-CSF transcript and showed endogenous megakaryocytic colony growth were those having a significantly higher platelet count than the group of patients without GM-CSF transcript and with no endogenous megakaryocytic colonies. In conclusion, these results suggest that GM-CSF, but not IL-1, participates in the production of spontaneous megakaryocytic colony formation observed in some CML patients. The true autocrine or paracrine nature of this stimulation remains to be established. PMID- 8350621 TI - Dynamics of interaction between DNA-specific antitumor agents and serum-contained cytokines in the initiation of ML-1 human myeloblastic leukemia cell differentiation. AB - When added to RPMI-1640 medium containing fetal bovine serum, DNA-directed antineoplastic agents such as cytosine arabinoside (araC), daunorubicin, and actinomycin D induce the monocytic differentiation of ML-1 human myeloblastic leukemia cell populations to an extent that depends upon both drug and serum concentration. Differentiation is not induced in the absence of serum or when antibodies to tumor necrosis factor-alpha and transforming growth factor-beta are added to the cultures, indicating that these serum-contained cytokines participate in initiating the differentiation process. The drug- and cytokine dependent cell maturation, which results in the inhibition of leukemic cell growth, is achieved at much lower concentrations of drug than is required for growth-inhibition through drug-mediated cell kill. RNA- and protein-targeted agents cannot replace DNA-specific agents in the process of differentiation induction. The DNA-specific agents render the leukemic cells responsive to the low concentrations of differentiation-inducing cytokines that are present in serum, causing them to mature, and subsequently, to cease growth. This sensitization may be a component of the clinically selective action of DNA specific antitumor agents. PMID- 8350622 TI - Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia. AB - We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA. PMID- 8350623 TI - Prognostic features and survival in young adults with early/intermediate chronic lymphocytic leukemia (B-CLL): a single institution study. AB - Information regarding natural history and prognostic factors for early/intermediate B-cell chronic lymphocytic leukemia (B-CLL) in young adults is limited. We analysed 62 young adults (< or = 50 years old) with early/intermediate B-CLL who were seen at our institution during initial diagnosis over a 15-year period. These patients had been followed for a median duration of 7 years. Median age for the entire group was 44 years and 72% were > or = 40 years old. Actuarial median survival from initial diagnosis for the entire group was 140 months. Upon univariate analysis, significant survival advantage was observed in patients with Rai stages 0 and 1 versus stage II disease (median survival 140 versus 60 months, p = 0.01) and in those with lymphocyte doubling time (LDT) of > 1 year versus < or = 1 year (median survival 150+ versus 94 months, p = 0.06). Similarly there was a trend towards longer survival in patients with a leucocyte count of < or = 50,000/microliters when compared to those with higher counts although the difference was not statistically significant. The bone marrow infiltration pattern was not prognostically useful. Upon multivariate analysis, only Rai stage and LDT were prognostically useful. Patients who did not respond to initial therapy with alkylating agents had the worst prognosis, with a median survival of only 19 months. Assessment of presenting clinical stage, LDT, and degree of initial treatment response may prompt earlier consideration of alternative therapeutic modalities such as purine nucleoside analogs or bone marrow transplantation in younger patients with early/intermediate B-CLL. PMID- 8350624 TI - Long-term follow-up of treatment and potential cure of adult acute lymphocytic leukemia with MOAD: a non-anthracycline containing regimen. AB - A total of 55 previously untreated adults with acute lymphocytic leukemia (ALL), median age 38 years (range 15-73 years), were treated with MOAD (methotrexate, vincristine, L-asparaginase, and dexamethasone). This regimen includes five phases--induction, consolidation, cytoreduction, maintenance, and central nervous system (CNS) prophylaxis with parenteral high-dose methotrexate. Of the 55 evaluable patients, 42 achieved complete remission 76%), with a median CR duration of 12+ months (range 0.5-195+ months). The median survival in remission is 22+ months (range 1-198+ months), with 33% of remitters continuing in long term remissions (> 5 years). Two out of four patients who developed CNS leukemia did so without marrow relapse, were successfully treated for that complication, and continue in total complete remission at 8+ and 16+ years. Another patient with extramedullary relapse (breast) was treated with radiation to that site and remains in total CR at 16+ years. Expected toxicities included myelosuppression during the induction phase of treatment, with 65% of patients requiring intravenous antibiotics. Mucositis was the next most frequent toxicity and required dose-reduction in seven patients. Minimal toxicity was seen during the post-remission phases of treatment. L-Asparaginase toxicity was more prominent during intravenous administration (24 patients) than when the intramuscular route of administration (30 patients) was used. The remission rate and long-term survivorship achieved with this regimen, without the use of an anthracycline, is comparable to that of other regimens for adult ALL. MOAD was well-tolerated by young and old adults with ALL. Aseptic necrosis of bone, successfully treated in each instance, occurred in four long-term disease-free survivors. The effect of this complication and its treatment on quality of life has been negligible. PMID- 8350625 TI - Soluble Fc gamma RIII is present in lower concentrations in the serum of patients with acute myelogenous leukemia (AML): a retrospective study. AB - Fc gamma RIII is a low affinity immunoglobulin G receptor expressed by neutrophils, natural killer cells, and macrophages. Soluble forms of Fc gamma RIII have been identified in serum, plasma, and other body fluids. Previous studies showed that Fc gamma RIII appeared late in myeloid differentiation. This retrospective study was designed to measure the concentration of soluble Fc gamma RIII in serum from patients with acute myelogenous leukemia (AML), a disease generally characterized by granulocytopenia and an increase in circulating myeloblasts and occasionally promyelocytes. Frozen serum samples from patients with AML and from age-matched normal donors were obtained from the Biological Carcinogenesis Branch Repository of the National Cancer Institute. We used an ELISA to measure the concentration of soluble Fc gamma RIII in these serum samples and observed significantly lower concentrations of soluble Fc gamma RIII in the serum of AML patients. The mean concentration of soluble Fc gamma RIII was 9.5 nM in normals (n = 48) and 5.4 nM in AML patients (n = 46), (p < 0.0005). Whether this difference is due to defects in granulopoiesis in these patients or to other parameters of the disease is unknown at this time. Our retrospective study should provide the basis for subsequent investigation of patients with AML to correlate soluble Fc gamma RIII concentrations with the clinical status of the patients. PMID- 8350627 TI - Efficacy and toxicity of 9-beta-D-arabinofuranosylguanine (araG) as an agent to purge malignant T cells from murine bone marrow: application to an in vivo T leukemia model. AB - 9-beta-D-Arabinofuranosylguanine (araG), an analog of deoxyguanosine which is not degraded by purine nucleoside phosphorylase, has been previously shown in in vitro studies by our laboratory to be effective in purging malignant T cells from human bone marrow (1). We now describe studies in a murine model of T-cell acute lymphoblastic leukemia (ALL) in which we tested whether bone marrow, contaminated with malignant T cells and purged ex vivo with araG, could reconstitute both the lymphoid and myeloerythroid lineages in the absence of leukemic relapse. The model utilized 6C3HED tumor cells, derived from a Thy 1.2+ malignant murine T cell line, which were shown to cause lethal leukemia in C3H/HeN mice. Intravenous injection of 10(6) 6C3HED cells resulted in 100% mortality within 18 days, with autopsy revealing tumor infiltration of multiple organs. 100% of non-leukemia bearing lethally irradiated C3H/HeN mice transplanted with syngeneic bone marrow, treated ex vivo with 100 microM of araG for 18 hours, survived > 365 days post transplant with full lymphohematopoietic reconstitution. Evidence of araG's ability to purge bone marrow of malignant tumor cells without causing significant toxicity to normal marrow derived hematopoietic progenitor cells was documented in experiments in which 75% of lethally irradiated mice transplanted with syngeneic bone marrow, contaminated with 6C3HED tumor cells and treated ex vivo with 100 microM araG for 18 hours, survived for > 250 to > 400 days. Death in 25% of mice was secondary to infection which developed before marrow reconstitution occurred. Reconstitution of the lymphoid, myeloid, and erythroid lineages with donor cells in surviving mice was documented. The data presented indicate that araG may effectively purge bone marrow of malignant T cells without irreversible toxicity to hematopoietic stem cells. This purging regimen is recommended for consideration for clinical trials in patients with T-cell malignancies undergoing autologous bone marrow transplantation and may also be a viable option for T-cell depletion as a strategy to prevent graft-versus-host disease. PMID- 8350626 TI - Mixed phenotype murine leukemias. AB - Cell lines were derived from eight individual leukemias induced by X-rays in NFS mice. First typed as null cells (surface immunoglobulin negative, Thy-1 negative), they turned out to have a mixed phenotype with myeloid cytochemical markers, pre-B surface antigens and molecular markers of pro-B lymphocytes. They represent murine models for mixed phenotype (pro-pre-B-myeloid) leukemias. PMID- 8350628 TI - New xenografts of human megakaryoblastic cell line (MEG-01) for evaluating anti tumor agents. AB - A human megakaryoblastic cell line (MEG-01) was successfully transplanted into athymic nude mice. MEG-01 cells (5 x 10(7)) were inoculated subcutaneously in KSN nu/nu mice, none of which were pretreated with irradiation or chemotherapeutic agents. All mice developed solid tumors at the site of injection after incubation for 10-14 days reaching a size of 200-400 mm2 (product of cross-sectional diameters) after 30 days. These tumors, designated as MEG-01/nu, were transplanted into other nude mice. The transplanted tumors infiltrated the liver and spleen, and leukemic megakaryoblastic cells appeared in the blood of some transplanted mice. Cells resuspended from MEG-01/nu tumors exhibited almost the same megakaryocytic characteristics as the original MEG-01 cells, and underwent in vitro differentiation to a mature form of megakaryocyte upon addition of phorbol diesters. MEG-01/nu was evaluated for sensitivity to cytosine arabinoside, vincristine, and daunorubicin in vitro and in vivo. Daunorubicin exhibited significant anti-tumor activity against MEG-01/nu in vivo, while cytosine arabinoside did so in vitro. Vincristine showed no activity against these cells. This cell line may provide a useful model for testing the in vivo efficacy of anti-tumor agents and immunotoxins, and for studying the pathophysiological mechanisms of human megakaryoblastic leukemia. PMID- 8350629 TI - In vivo development of an acetyldinaline resistant subline of the BN rat acute myelocytic leukemia (BNML). AB - The cytostatic drug acetyldinaline [ACD, CI-994, 4-acetylamine-N-(2-aminophenyl) benzamide] shows an extreme antileukemic effect in the Brown Norway (BN) rate model for acute myelocytic leukemia (BNML) with only minor toxicity for normal pluripotent hemopoietic stem cells. So far, the mode of action is unknown. A resistant subline (BNML/ACD-R) was developed in vivo in the BNML model. Leukemic rats received repeated oral administrations of ACD. When the leukemia relapsed after initial remission-induction with ACD, the cells were transferred to new recipients which were again treated. In total, the animals received 247 oral administrations of ACD (33 x 2 mg/kg per day and 214 x 5 mg/kg per day) before full resistance was reached. The cell line was transferred 17 times in total. Treatment of the final resistant cell line with therapeutically highly active doses of 23.7 mg/kg per day and 11.85 mg/kg per day ACD for 5 days, that resulted in an increase of life span (ILS) of 57 and 18 days, respectively, when applied to the sensitive parent BNML line (BNML/S), resulted in only 10 and 3 days ILS, respectively. These results indicate that a significant degree of resistance has been achieved, which can be overcome partially by increasing the dose of ACD. Whether the development of a resistant subpopulation of the BNML is a result of acquired resistance or whether a naturally resistant subpopulation has been selected out after prolonged treatment with ACD remains to be established. The currently available resistant subline BNML/ACD-R now offers the possibility for further studies on the mechanism of action of ACD. PMID- 8350630 TI - Absence of amplification of MDM2 gene, a regulator of p53 function, in myelodysplastic syndromes. AB - The MDM2 gene is a gene whose product binds to p53 and regulates its function. Amplification of MDM2 has been found in human sarcomas, where it leads to inactivation of p53. In 64 cases of generally advanced myelodysplastic syndromes, we found no amplification or rearrangement of MDM2 gene by Southern analysis. MDM2 RNA was also normal in the 15 cases where Northern analysis was made. Thus, amplification of MDM2 is not seen or must be very rare in myelodysplastic syndrome (MDS). Because P53 gene mutations are not frequent in MDS, inactivation of p53 seems to be, overall, a rare pathogenetic event in MDS. PMID- 8350631 TI - Identification of an altered immunoglobulin heavy-chain gene rearrangement in the central nervous system in B-precursor acute lymphoblastic leukemia. AB - In B-precursor acute lymphoblastic leukemia (ALL), the nucleotide sequence of the complementarity determining region III (CDRIII) in the rearranged immunoglobulin heavy chain gene (IgH) has been used as a molecular fingerprint to identify the leukemic cells. In a child with B-precursor ALL without central nervous system (CNS) disease at diagnosis and a subsequent isolated CNS relapse, we examined the stability of the rearranged IgH by comparing the nucleotide sequences of the CDRIII in the leukemic cells from the marrow at diagnosis to the sequences in the leukemic cells from the cerebrospinal fluid at relapse. Whereas two of the three IgH sequences isolated from the leukemic cells at CNS relapse were identical to sequences originally isolated from the marrow lymphoblasts at diagnosis, the third CNS sequence was similar but not identical to the third marrow sequence. The third IgH sequence identified in the CNS differed from the marrow sequence only at the variable gene segment adjoining the CDRIII. Using a detection method based on the polymerase chain reaction, the altered IgH sequence identified in the leukemic cells from the cerebrospinal fluid was noted to be present in the CNS at a higher frequency than the related diagnostic sequence and was not detected in the marrow either at diagnosis or at CNS relapse. These findings indicate that the clonal pattern of leukemia in the CNS may differ from that in the marrow. PMID- 8350632 TI - Interferon alpha and gamma alter the binding of progenitor cells to fibronectin of patients with CML. PMID- 8350633 TI - Molecular evidence of minimal residual disease after treatment for leukaemia and lymphoma: an updated meeting report and review. AB - The very rapid development in the last few years of techniques based on use of the polymerase chain reaction (PCR) for characterizing molecular lesions in leukaemia and lymphoma now offers the opportunity for monitoring residual disease at a sensitivity of one malignant cell in 10(5) or 10(6) normal cells. Maximal specificity is presumably achieved when the DNA sequences amplified are truly leukaemia-specific, such as BCR/ABL in chronic myelogenous leukemia, RARA PML/RARA in t(15;17) acute myelogenous leukemia, DEK/CAN in t(6;9) AML, PBX1/E2A in t(1;19) acute lymphoblastic leukemia (ALL), or TAL-1 deletions in other T ALLs. Comparable sensitivity may be achieved by using immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) gene rearrangements if a clonospecific probe can be generated. However, the presence of similar sequences in IgH genes from normal B lymphocytes may decrease the specificity. For clinical purposes the crucial issues are the following. Can PCR techniques be used for confirmation of diagnosis and evaluation of extent of disease? Can PCR data obtained in remission provide information about the probability of cure or of relapse? Can techniques be developed to quantitate the PCR product and thereby increase its predictive value? These and other issues were addressed at the 4th Workshop of the Molecular Biology/BMT Study Group that took place in Bristol UK on 9-10 May 1992. PMID- 8350634 TI - Dr. Melvin C. Millet, early Mayo partner and urologist. PMID- 8350635 TI - Oligodendrocyte injury is an early event in lesions of multiple sclerosis. AB - The ultrastructural features of 11 stereotaxic brain biopsy specimens that demonstrated inflammatory primary demyelination consistent with acute multiple sclerosis were examined. Uniform widening of inner myelin lamellae (biphasic myelinopathy) and degeneration of inner glial loops ("dying-back" oligodendrogliopathy) were early pathologic abnormalities that antedated complete destruction of myelin sheaths. Perivascular inflammatory cells (lymphocytes, macrophages, and occasional plasma cells) were in intimate contact with degenerating myelin sheaths. The response of astrocytes was prominent, even in areas of minimal demyelination. Oligodendrocytes were morphologically preserved in early lesions but proliferated at the periphery of active lesions. Thinly myelinated axons indicative of central nervous system-type remyelination by oligodendrocytes were observed primarily at the edge of plaques. Disturbances of the myelinating function of oligodendrocytes--unaccompanied by death of these cells--may be among the earliest pathologic features in multiple sclerosis. PMID- 8350636 TI - Myocardial revascularization before abdominal aortic aneurysmorrhaphy: effect of coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty (PTCA) has assumed an increasing role in the preoperative preparation of patients with an abdominal aortic aneurysm (AAA). The influence of this modality on perioperative morbidity and long-term outcome has not been substantiated. To determine the effect of PTCA, we analyzed a cohort of 2,452 patients who underwent repair of an AAA between 1980 and 1990 at our institution. We compared the cardiac morbidity, mortality, and survival of patients who had preoperative coronary revascularization by PTCA or coronary artery bypass grafting (CABG). The overall perioperative mortality for the 2,452 patients was 2.9%. Preoperative coronary revascularization was necessary in 100 patients (4.1%)--86 had CABG and 14 had PTCA. Of these 100 patients, 95% had cardiac symptoms. Patients selected for PTCA, in comparison with CABG, had significantly less three-vessel disease but not significant differences in cardiac history or ejection fraction. During the study period, the use of PTCA increased significantly. The perioperative rate of myocardial infarction for patients with prior CABG was 5.8% in comparison with 0% for those with prior PTCA. No hospital deaths occurred in either group. The median interval between coronary revascularization and repair of an AAA was 10 days for PTCA and 68 days for CABG. The 3-year survival was not statistically different between CABG (82.8%) and PTCA (92.3%) groups. The rate of late cardiac events (at 3 years) was 56.5% in the PTCA group and 27.3% in the CABG group. We conclude that PTCA as part of a highly selective approach to coronary revascularization before repair of an AAA minimizes cardiac-related events and death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350637 TI - Clinical features and differential diagnosis of aortic dissection: experience with 236 cases (1980 through 1990). AB - Acute aortic dissection is the most common fatal condition that involves the aorta; nevertheless, despite major advances in noninvasive diagnosis, the correct antemortem diagnosis is made in less than half the cases. To promote continued improvement in the prompt recognition of aortic dissection, we present a review of the Mayo Clinic experience with 235 patients who had 236 substantiated aortic dissections. At the time of initial assessment, 158 patients (67%) had acute and 78 patients (33%) had chronic aortic dissection. Hypertension was the most common predisposing factor (78% of patients overall). The acute onset of severe chest pain was the most common initial complaint (74%), but 33 patients (15%) had painless aortic dissection and abnormal chest roentgenographic findings. Less common manifestations included congestive heart failure, syncope, cerebrovascular accident, shock, paraplegia, and lower extremity ischemia. The initial clinical impression was aortic dissection in 62% of patients overall. In 17 patients (28%), the correct diagnosis was not made before postmortem examination. Although the clinical features of aortic dissection have gained wider appreciation, the diagnosis still remains unsuspected in a substantial number of patients. In a patient who has a catastrophic illness and unexplained symptoms that could be of vascular origin, especially in the presence of chest pain, aortic dissection should always be included in the differential diagnosis. PMID- 8350638 TI - Herpes zoster-associated meningoencephalitis in patients with systemic cancer. AB - We reviewed the experience at the Mayo Clinic with neurologic complications related to herpes zoster in patients with systemic cancer. Aside from pain, the most common neurologic complication was zoster-associated meningoencephalitis, which occurred in 9 of 1,125 patients. In these nine patients, the most common underlying malignant lesions were chronic lymphocytic leukemia and lymphoma. All patients in whom meningoencephalitis developed had trigeminal zoster or disseminated zoster. The primary neurologic symptoms were headache, confusion, and somnolence. Nuchal rigidity and fever were uncommon. The response to treatment with acyclovir was generally favorable. PMID- 8350639 TI - Quantification of human plasma apolipoproteins C-I, C-II, and C-III by radioimmunoassays. AB - We have developed radioimmunoassays for the quantification of apolipoproteins (apo) C-I, C-II, and C-III in human plasma. The apo C proteins were isolated from very low-density lipoproteins of patients with hypertriglyceridemia, fractionated on a Sephacryl column, and purified by diethylaminoethyl cellulose anion-exchange chromatography followed by reverse-phase fast protein liquid chromatography. The assays were sensitive, specific, and reproducible, and the standards demonstrated parallel immunoreactivity with plasma samples. Patients with hypertriglyceridemia (triglyceride level more than 2,200 mg/liter)--14 patients with diabetes and 12 with type V hyperlipoproteinemia--were compared with age- and sex-matched control subjects. In comparison with the control groups, levels of apoproteins C-I, C-II, and C-III were significantly increased in both disease groups, but the ratios of the C peptides to triglycerides were significantly lower, an indication of a relative deficiency of C apoproteins in hypertriglyceridemic states. Independent radioimmunoassays for each of the C apolipoproteins would help to study their individual roles in triglyceride-rich lipoprotein metabolism. PMID- 8350640 TI - Postoperative irradiation for tonsillar carcinoma. AB - From January 1975 through July 1987 at the Mayo Clinic, 16 patients received postoperative adjuvant radiation therapy for squamous cell carcinoma of the tonsil (pathologic stage I in 4 patients, stage III in 3, and stage IV in 9). Follow-up was continued for a minimum of 2 years or until death. At 5 years, overall survival was 74% and disease-free survival was 68% for the entire group of patients. The local-regional control rate at 5 years was 83% for 12 patients with pathologic stage III or IV disease; the 5-year disease-free survival rate was 74%. The results with use of postoperative irradiation for stage III or IV tonsillar cancer seem superior to those for a similar historical group of patients who underwent surgical treatment only. Because the number of patients was small and the analysis was retrospective, our study may have included some undetected bias. PMID- 8350641 TI - Ancillary therapies in the management of lung cancer: photodynamic therapy, laser therapy, and endobronchial prosthetic devices. AB - Endoscopic therapy for cancer that involves the tracheobronchial tree is currently available for two distinct types of lesions: radiographically occult superficial squamous cell carcinoma and advanced malignant tumors that cause severe airway obstruction. Photodynamic therapy, which uses a photosensitizing agent, is effective for managing early superficial squamous cell carcinoma. Neodymium:yttrium-aluminum-garnet laser therapy has been effective in the palliative management of patients with advanced or recurrent malignant obstructive airway lesions, either alone or in combination with intraluminal radiation therapy. Most recently, endobronchial prosthetic devices (stents) have been used in patients with advanced airway obstruction. The use of each of these modalities in the management of lung cancer is reviewed. PMID- 8350642 TI - Chronic diarrhea in diabetes mellitus: mechanisms and an approach to diagnosis and treatment. AB - In this study, our aim was to develop a practical strategy to facilitate the management of patients with diabetes mellitus and chronic diarrhea in a tertiary referral practice. We reviewed the pertinent English-language literature of the past 30 years that described the pathophysiologic mechanisms and treatment of patients with diabetic diarrhea and retrospectively reviewed the medical records of all patients with diabetic diarrhea examined at the Mayo Clinic during 1990. Three typical case studies are described to illustrate the diverse mechanisms that lead to chronic diarrhea in patients with diabetes. No report in the literature has systematically evaluated all the putative mechanisms of chronic diarrhea in any group of patients with diabetes. In our tertiary referral practice, diabetic diarrhea was frequently due to celiac sprue, bacterial overgrowth in the small bowel, or fecal incontinence in conjunction with anorectal dysfunction; however, in almost 50% of the patients, these causes were excluded, and abnormal intestinal motility or secretion was postulated to be one of the likely causes of the diarrhea. These data suggest a practical algorithm based on three sequential assessments: first, tests of blood and stool specimens and flexible sigmoidoscopy to detect evidence of malabsorption or disease in the distal colon; second, small bowel aspirate and biopsy if the results of initial blood or stool tests are abnormal or anorectal function tests if those test results are normal; and, finally, measurement of gastrointestinal transit or therapeutic trials with opioids, clonidine hydrochloride, and, rarely, cholestyramine resin or octreotide acetate (or both methods). The mechanisms whereby abnormal neural function due to diabetes results in altered digestive, secretory, absorptive, or motor function necessitate further elucidation. The management of chronic diarrhea in patients in a tertiary referral practice, however, can be based on a practical algorithm to determine the cause and to adopt specific treatment to correct it. PMID- 8350643 TI - Early thrombotic stenosis of aortic bioprosthetic valves: report of two cases. AB - Thrombotic stenosis of a Carpentier-Edwards porcine bioprosthesis occurred in two patients within 3 months after aortic valve replacement. Both patients underwent successful replacement of the aortic prosthesis. Although previously reported, this complication of aortic porcine bioprostheses is uncommon. PMID- 8350644 TI - Georg von Bekesy--audiology and the cochlea. PMID- 8350645 TI - Giant pseudodiverticulum of the sigmoid colon. PMID- 8350646 TI - Near the conflagration: the wide duty to warn. AB - The "duty to warn" has become fixed in US law since the 1976 case of Tarasoff v Regents of the University of California. In that case, the California Supreme Court decided that psychotherapists whose patients make a specific, serious threat of violence against a specific, clearly identifiable potential victim have a duty to warn the intended victim, directly or indirectly, of the threat. Tarasoff inspired several successful and unsuccessful lawsuits. A recent Vermont case has extended the duty to warn in that state to a threat of damage to property when persons may be physically harmed. The duty to warn is explicitly based on considerations of social utility and, as such, is attractive for courts to expand because an apparently minimal effort by therapists will often prevent substantial harm to victims. Some states have codified the duty to warn in a statute, but other states have refused to adopt the Tarasoff reasoning. In the absence of clear legal decisions to the contrary, psychotherapists may well anticipate that the duty to warn operates in their states. PMID- 8350647 TI - Multiple sclerosis: new insights from old tools. PMID- 8350648 TI - Myocardial revascularization before repair of an aortic aneurysm. PMID- 8350649 TI - Percutaneous endoscopic gastrostomy. PMID- 8350650 TI - The radiation-sensitive mutant rad-8 of Caenorhabditis elegans is hypersensitive to the effects of oxygen on aging and development. AB - A mutant of rad-8, originally isolated on the basis of its hypersensitivity to ultraviolet radiation, is also hypersensitive to oxygen and methyl viologen, a superoxide-anion generator. Oxygen also retarded development and reduced fecundity in a concentration-dependent fashion in rad-8 but not in wild type. In addition, the mean life span of rad-8 (but not wild type) was progressively shortened when animals incubated in increasing oxygen concentrations. This cross hypersensitivity to both UV radiation and free radicals provides further evidence that DNA damage may be important in the aging process. PMID- 8350651 TI - Estimation of reference intervals from a SENIEUR protocol compatible aged population for immunogerontological studies. AB - Because many laboratory values change with age, the study of healthy aging as well as diagnosis of disease in geriatric patients requires specific age corrected reference intervals. We have established such reference intervals for a healthy population aged 65-74 years by selection of a sample group applying the clinical criteria of the SENIEUR protocol and we have compared them with those of a young control group (20-33 years) fulfilling the same criteria. Significant or minor elevations were seen, e.g. for plasma concentrations of fasting glucose, urea, total and LDL-cholesterol, triglycerides, gamma-glutamyl-transferase, alkaline phosphatase, erythrocyte sedimentation rate and serum neopterin levels. These reference intervals can be used for selecting a SENIEUR compatible population aged between 65 and 74 years. Additionally, plasma lipid parameters (cholesterol, triglycerides) are proposed to be included in the SENIEUR protocol. PMID- 8350652 TI - Influence of electrical stimulation on enzymatic activity of old rat muscles during hindlimb suspension. AB - 1. The purpose of this study was to determine the effects of electrical stimulation on the muscles of older rats (21-24 months old) during suspension hypokinesia/hypodynamia. The rats' hindlimbs were suspended for three weeks, after which the activities of three enzymes were measured in the extensor digitorum longus, the medial gastrocnemius and the soleus muscles. 2. The activity of phosphofructokinase decreased in the soleus muscle and in the white part of the medial gastrocnemius muscle. Malate dehydrogenase and beta hydroxyacyl-CoA-dehydrogenase showed decreased activity in the red part of the medial gastrocnemius muscle. 3. When electrical stimulation was applied, the activity of the glycolytic enzyme phosphofructokinase increased substantially in all studied muscles. The activity of the malate dehydrogenase and beta hydroxyacyl-CoA-dehydrogenase enzymes was not influenced by electrical stimulation in the majority of the studied muscles. 4. These results suggest that our electrical stimulation model not only prevents loss of phosphofructokinase activity of aged muscles but increases the activity of anaerobic glycolysis metabolism without affecting the oxidative and fatty acid pathways. PMID- 8350653 TI - Phencyclidine-binding sites in mouse cerebral cortex during development and ageing: effects of inhibitory amino acids. AB - The binding of N-[1-(2-thienyl)cyclohexyl]-[3H]piperidine ([3H]TCP) to the phencyclidine-binding sites in the N-methyl-D-aspartate (NMDA) receptor complex associated ion channel was characterized in cerebral cortical membranes from 3 day-old to 24-month-old mice. The binding was saturable, exhibiting only one binding component during the whole life-span studied. The maximal binding capacity Bmax, calculated per protein content, decreased during postnatal development until 3 months of age, remaining thereafter constant in ageing mice, thus indicating the greatest availability of phencyclidine-binding sites in the immature cerebral cortex. The binding constant KD increased during the first postnatal week, remained thereafter unchanged and increased again during the second year of life, indicating a decreased affinity of the receptor sites for the ligand. The general properties of the binding; potentiation by glutamate and NMDA, as well as by glycine in a strychnine-insensitive manner, prevailed during development and ageing, certain of these effects being however less pronounced in the immature brain. Taurine and beta-alanine stimulated TCP binding, acting probably at the glycine modulatory site. The actions of these inhibitory amino acids were weak and inconsistent when compared to that of glycine. Since NMDA receptors have been suggested to be involved in neuronal plasticity and learning and memory processes, these modifications in the properties of cortical phencyclidine-binding sites might be of importance in the regulation of excitatory amino acid functions during development and ageing. PMID- 8350654 TI - Cross-sectional Gompertzian analysis: the development of a Gompertz mortality ratio (GMR) and its applicability. AB - Many conventional epidemiological analyses of the distribution and aetiology of disease employ standardised mortality ratios (SMRs) as a basis upon which to evaluate comparative studies of disease in populations. However SMRs, whilst constructed to control for age and sex, are not capable of incorporating other variables such as life expectancy which has been demonstrated to be of crucial importance in understanding the changing relationships between mortality from different causes. The development of a Gompertz mortality ratio (GMR) and its application to recent mortality from amyotrophic lateral sclerosis (ALS) in the Counties of England and Wales illustrates the value of substituting GMRs for SMRs in the analysis of competitive relationships between conditions, especially those associated with enhanced life expectancy. PMID- 8350656 TI - Ageing in the autonomic nervous system: a result of nerve-target interactions? A review. AB - There are few generalisations that can be made regarding the changes that occur in autonomic nerves during ageing. Old age has different effects, including loss of neurones, loss of axon branches and alterations in neurotransmitters and other intracellular features. However, these age-related events are associated with particular and often small groups of neurones and are frequently species specific. Changes occur at different periods during development and maturity without any obvious age-stage at which neurodegenerative changes come to predominate. Some of the observations regarding neuronal changes in old age can be interpreted as the result of altered interactions between neurones and their peripheral target tissues. Recent studies in my laboratory support this contention. The neurotrophic theory has been used to explain such interactions during early development and it seems possible that, for example, alterations in the access of neurones to target-derived growth factors may underlie some of the changes that have been observed in old age. Plasticity in the mature autonomic nervous system may also be governed by similar relationships between nerves and their target tissues. PMID- 8350655 TI - Cell proliferation by cell cycle analysis in young and old dietary restricted mice. AB - The effect of dietary restriction (DR) on cell proliferation determined by cell cycle analysis in tissues of young and old mice was investigated. Using the percentage of S-phase cells as an index of cell proliferation, we found that DR inhibited cell proliferation in spleen and thymus in young mice. No significant changes were found in bone marrow and kidney in the ad libitum (AL) or DR mice regardless of age. In old mice, the DR effect was observed in spleen only. When age increased, a parallel decline in cell proliferation was evidenced by a reduced % of S-phase cells. DR produces a greater cell cycle effect in the young mice than in the old mice. The present data suggests that inhibition of cell proliferation by DR may be affected by type of tissue, age, length of DR, and capacity or rate of cell proliferation. PMID- 8350657 TI - Influence of photosensitizers and light on the life span of Drosophila. AB - The life span of adult Drosophila melanogaster fruit flies changed when they were fed two different photosensitizers. Methylene blue decreased the median life span by 49% when present in the food at a concentration of 0.001 M. Another photosensitizer, riboflavin, produced no changes in life span under the same conditions of a 12:12 h light/dark cycle at a daytime light intensity of 1000 lux. Flies exposed to constant darkness lived 43.2% longer than those exposed to constant light at a light intensity of 2000 lux. Under these conditions, riboflavin increased the life span of the flies exposed to constant light by as much as 25%. We conclude that riboflavin confers some degree of protection against the effects of constant light exposure. The completely different results obtained with riboflavin and methylene blue suggest a possible mechanism for photoageing involving photodynamic action mediated through the production of singlet oxygen. PMID- 8350658 TI - Energy restriction suppresses microsomal Ca(2+)-ATPase activities in various organs in C57BL/6 female mice in both euthermic and torpor states. AB - C57BL/6 female mice were fed a daily control diet (n = 5, 3.9 g/day, 95 kcal/week) or ER diet (n = 5, 2.3 g/day, 48 kcal/week) at 1800 h from 6 weeks of age. Telemetry, conducted at 6 months of age, confirmed that all ER mice entered daily torpor (core body temperature less than 31 degrees C) for 6.63 +/- 2.34 h/day while control mice were euthermic (> 35 degrees C). In vitro activities of microsomal Ca(2+)-ATPase were determined in the brain, liver, salivary gland and kidney from these mice at 6 months of age. Assays were performed at three incubation temperatures of 37 degrees C, 31 degrees C and 25 degrees C. In assays at 37 degrees C, the activities of Ca(2+)-ATPase in the brain and salivary gland from ER mice were lower than those in corresponding organs from control mice. The suppression became profound as the incubation temperature decreased. On the other hand, at 37 degrees C Ca(2+)-ATPase activities in the liver and kidney from ER mice were not lower than those in corresponding organs from control mice, but decreased significantly at low temperatures. Microsomal Ca(2+)-ATPase activities thus appeared to be reduced in ER mice, although it remains unknown whether the present results represent reduced in vivo capacities to regulate cytosolic Ca2+ concentrations. PMID- 8350659 TI - The effects of age on immune responses in the antigen-instilled dog lung. Antibody responses in the lung and lymphoid tissues following primary and secondary antigen instillation. AB - To evaluate the effects of age on immunity induced by lung immunization, 11 aged (12-17 years; median age = 14) and 12 young (2-5 years) male Beagle dogs were instilled with 10 mg of keyhole limpet hemocyanin (KLH) in the right cardiac lung lobe and 10(10) sheep red blood cells (SRBC) in the left cardiac lung lobe. Five aged and six young dogs were sacrificed at day 9 after primary antigen instillation. The remainder were given challenge antigen instillations of KLH and SRBC at day 21 and sacrificed 7 days later. Serum, bronchoalveolar lavage fluid and lung tissue from immunized and control lobes, tracheobronchial, mesenteric and popliteal lymph nodes, spleen, and blood were taken at sacrifice. Anti-KLH IgA, IgG and IgM antibody production by cells in lung tissue and lavage fluid from the KLH-exposed lobe was lower at primary immunization and challenge in aged than young dogs. Lavage fluid IgA and IgG levels from the KLH exposed lobe at primary immunization and challenge were lower in aged versus young dogs, while IgM levels were lower only after primary immunization. Localized lung immune memory responses were also markedly lower in aged dogs when compared with young dogs. Anti-SRBC responses were similar to the anti-KLH responses. Our data show that systemic immune responses are significantly lower in aged dogs following primary antigen instillation, but not after antigen challenge in the lung. This was not the case for localized lung immune responses, which were significantly lower in aged dogs even following antigen challenge. The data also show that antibody production by lavage cells is a good index of interstitial lung cell antibody production. PMID- 8350660 TI - Hypotonic fragility of outer membrane and activation of external pathway of NADH oxidation in rat liver mitochondria are increased with age. AB - Great importance is attached to structural and functional deterioration of mitochondria as a reason for ageing of an organism; the attention of many scientists has been concentrated on such questions as age changes in the system of oxidative phosphorylation, damage of mitochondrial DNA by free radicals generated in the respiratory chain and inclusion of some fragments of mitochondrial DNA into the nuclear genome. Mitochondrial high amplitude swelling in a cell under some extreme conditions can possibly play a very important role in mechanisms of deterioration of energy transformation function, in activation of lipid peroxidation and mitochondrial DNA damage as a result of outer membrane disruption and release of enzymes from the intermembrane space (e.g. superoxide dismutase amd adenylate kinase). In this work the age changes of the hypotonic fragility of the outer membrane of rat liver mitochondria and the activation of the external, rotenone-insensitive pathway of NADH oxidation have been examined. It is shown that the obligatory condition for activation of rotenone-insensitive NADH oxidation is a break in the outer membrane and that the rate of NADH oxidation substantially increases in the presence of physiological concentrations of Mg2+ which cause a multiple increase in the affinity of the inner membrane to cytochrome c. Research on the rate of rotenone-insensitive NADH oxidation with respect to the osmotic pressure, the ionic strength of the medium, the presence of Mg2+ ions and cytochrome c in the medium has demonstrated a considerable increase in the hypotonic fragility of the outer membrane of liver mitochondria with age in male rats. In female rats the age changes were insignificant. It is supposed that the damage to the outer membrane of mitochondria in cells can serve as one of the possible explanations of both decrease in the reliability of an aged organism under extreme conditions and sex differences of life-span. PMID- 8350661 TI - Stimulation by the antioxidant thioproline of the lymphocyte functions of old mice. AB - Diet supplementation with thioproline (thiazolidine-4-carboxylic acid), an intracellular sulfhydryl antioxidant and free radical scavenger, may slow the aging process of metazoans and prolongs their life span. In the present experiment Swiss mice fed thioproline (0.07%, w/w) from 13 to 22 months of age were used. Six- and 22-month-old mice fed standard diet were used as controls. Two important functions of lymphocytes, the proliferative response to the mitogen Concanavalin A (Con A) and the mobility, both spontaneous and directed to a chemoattractant gradient (chemotaxis), were analyzed in lymphocytes from axillary nodes, spleen and thymus. Mobility and chemotaxis were studied by Boyden's technique, using filters of 3 microns pore diameter, 3 h of incubation and fmet leu-phe at 10(-8) M as chemoattractant. The proliferative response was estimated as 3H-thymidine incorporation in lymphocytes incubated for 72 h in the presence of Con A (1 and 5 micrograms/ml). The results show a decrease in mobility, chemotaxis and lymphoproliferative response in old mice in comparison to adults. However, a significant increase in these functions was observed in old mice fed thioproline. The advantage of using this antioxidant for immunostimulation during aging, a stage of life characterized by a decreased immune response, is discussed. PMID- 8350662 TI - Fructose 2,6-bisphosphate: changes during neonatal maturation and aging of rat and potential role in regulation of glucose utilization. AB - During the 6 days following birth, tissue levels of fructose-2,6-P2 in rat brain, liver, muscle, heart and kidney did not significantly change. However, by the tenth day postpartum fructose-2,6-P2 levels in brain, heart, and skeletal muscle increased approximately 50% and attained adult values. During maturation of liver, adult levels of fructose-2,6-P2 were not achieved until 3-4 weeks after birth or approximately at the time of maximum rates of gluconeogenesis. Renal fructose-2,6-P2 levels in the neonate were initially elevated and 2-3 weeks after birth decreased approximately 2.5-fold to adult values. With the exception of the pons-medulla, which showed no significant changes in fructose-2,6-P2 amounts, levels of this regulatory sugar from aging brain regions were generally decreased. The fructose-2,6-P2 levels from heart atria of old rats (24-30 month) were also significantly decreased. In diaphragm, the fructose-2,6-P2 levels were increased at 12 months of age and at 27 months of age were twice the level at 3 months. The fructose-2,6-P2 levels during the aging of liver, skeletal muscle (EDL and soleus), spleen, thymus, kidney, testis and lung were not significantly altered. PMID- 8350663 TI - Developmental aspects of Bufo bufo embryo glutathione transferases. AB - The expression of glutathione transferase isoenzymes has been studied during the development of Bufo bufo embryo. By analysing the GSH-affinity purified materials in terms of substrate specificities, SDS-PAGE pattern, HPLC elution profile, we conclude that, up to stage 22, no significant changes in the expression of glutathione transferases isoenzymes occurred during Bufo bufo embryo development. At stage 25 the distribution of glutathione transferases was found to be slightly different from those of all other foregoing stages. A marked decrease of embryonic glutathione transferases subunits with a parallel appearance of new structurally and immunologically different subunits was noted in toad liver and kidney. Toad ovary continued to express embryonic glutathione transferase subunits. PMID- 8350664 TI - Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: lessons from transgenic animal models. AB - In this study, we characterize transgenic mice carrying fusion genes, in which the genes coding for human (h) or bovine (b) growth hormone (GH) have been put under the transcriptional control of the mouse metallothionein I (MT) or the rat phosphoenolpyruvate carboxykinase (PCK) promoter as models for investigating the long-term effects of elevated GH on life expectancy. Circulating GH concentrations ranged from 3000 to 900,000 ng/ml, from 320 to 2960 ng/ml and from 34 to 1050 ng/ml in transgenic mice belonging to the MThGH, the PCKbGH and the MTbGH groups, respectively, and were high on a short-, medium-, and long-term basis. As a consequence of excess GH in their serum, GH transgenic mice exhibited drastically reduced life span which was primarily due to severe kidney lesions (glomerular hypertrophy, sclerosis and hyalinosis associated with tubulo interstitial changes) consistently found in these animals. Alterations of the liver observed in transgenic mice included both hepatocellular megaly and various degrees of regressive, regenerative and fibrotic changes. In older MTbGH and PCKbGH transgenic mice, hepatocellular neoplasms including both adenoma and carcinoma were frequently found in addition to non-neoplastic changes. Our study points out the suitability of GH transgenic mice to evaluate the effects of various levels of GH in long-term studies without having to take antibody production against the heterologous hormone into account. Findings in GH transgenic animals suggest that the long-term benefits and risks of GH therapy should be carefully evaluated. PMID- 8350665 TI - Endothelin-1-induced gastric ulcer is attenuated by cetraxate. AB - We investigated the effect of the anti-ulcer drug cetraxate on the development of the gastric ulcer induced by the submucosal injection of endothelin-1 in the rat gastric body, and its effects on gastric mucosal hemodynamics and tissue oxygenation by Laser doppler flowmetry and tissue spectrophotometry. Endothelin-1 induced gastric ulcer (ulcer length: 11.85 +/- 0.89 mm, mean +/- SEM, n = 4) which was strongly attenuated by cetraxate (ulcer length: 3.27 +/- 0.3 mm, mean +/- SEM, n = 8, p < 0.0001). Cetraxate maintained also tissue oxygenation without causing any significant effect on the endothelin-1-induced changes in gastric mucosal blood flow and volume. These results show that cetraxate exerts its cytoprotective action partly by maintaining mucosal oxygenation. PMID- 8350666 TI - Identification of specific pathways of communication between the CNS and NK cell system. AB - The specific signals and pathways utilized by the natural killer (NK) cell system and the central nervous system (CNS) that results in the conditioned response (CR) is not clearly understood. Single trial conditioning of the NK cell activity provides us with a model to probe the mechanisms of communication between two major systems (Immune and CNS) which are involved in the health and disease of the individual. The studies show that the IFN-beta molecules possess the properties attributed to the unconditioned stimulus (US). IFN-beta can penetrate the CNS and evoke the elevation of NK cell activity in the spleen. This unconditioned response (UR) can be linked to a specific conditioned stimulus (CS). Specific odors such as camphor provide a neural pathway for the CS to associate with the US. Evidence is presented that in conditioning there are two locations where memory develops. The CS/US association is made centrally and its memory is stored at a central location, but the memory for the specificity of the odor is presumably stored in the olfactory bulbs. The CS recalls the CR by triggering the olfactory neural pathway which, in turn, signals the hypothalamic pituitary axis to release mediators that modulate the activity of NK cells in the spleen. These results imply that through conditioning one has direct input into the regulatory hypothalamus that controls the internal environment of the organism and the health and disease of the individual. Consequently, it is not inconceivable that through this approach we might be able to alter the course of a disease process. PMID- 8350667 TI - Atrial natriuretic factor enhances the hydroosmotic response of toad bladder to submaximal doses of vasopressin. AB - Using the toad urinary bladder, we examined the effects of submaximal levels of atrial natriuretic factor (ANF) upon the hydroosmotic water flux caused by physiologic concentrations of vasopressin (VP). Pretreatment with ANF prior to the addition of VP (10(-9)M) significantly enhanced water transport (123 +/- 23%) compared to tissues exposed to VP alone. Pre-treatment with ANF also significantly enhanced the hydroosmotic response (143 +/- 43%) to cyclic-3',5' adenosine monophosphate (cyclic-AMP). When the concentration of VP was progressively increased during time course experiments, an inhibitory effect of ANF on water transport followed the early stimulatory response to this peptide. The data support a novel, dose-dependent modulatory role for ANF early in the response of transporting epithelia to VP. Moreover, the stimulatory effect of submaximal doses of ANF to cyclic-AMP mediated water transport suggest the possibility that modulation by ANF may occur at a site following the VP receptor linked adenylate cyclase system. PMID- 8350668 TI - External ions and direct membrane effects of enkephalins on Amoeba proteus. AB - We have shown that amphiphilic hormones like vasopressins and endorphins increase water permeability and activate the contractile vacuole (CV) in Amoeba by direct action on the plasma membrane. Using our standard CV assay, the effects of nine opioids, morphine, naloxone and 7 enkephalin derivatives, have been compared in normal, ion-containing growth medium (Chalkley's) and in glass-distilled water. While the absence of external ions does not affect the activity of molecules with net positive charges, opioids with no net charge are devoid of action in glass distilled water. This shows that, in addition to amphiphilicity, which permits insertion into the lipid core of the membrane, electrostatic interactions with ions and with negative charges of phospholipids membrane and glycocalyx, the thick glycoproteic cell coat of Amoeba, are important in the direct action of these compounds. PMID- 8350669 TI - Effects of a short term hindlimb suspension on central and peripheral norepinephrine turnover in rats. AB - The loss of appropriate cardiovascular reflexes which contributes to the cardiovascular deconditioning observed after an exposure to actual or simulated microgravity (in man or animals) is well known, but the mechanisms responsible remain unclear. This protocol, a 2.5 h hindlimb suspension in rats, was undertaken to study the early adaptation of the sympathetic neurons involved in arterial pressure regulation: we determined central norepinephrine (NE) turnover in the brainstem catecholaminergic cell groups responsible for the central cardiovascular regulation i.e. A1, A2 (rostral and caudal), A5 and A6 cell groups and peripheral NE turnover in target organs (heart and kidneys). The NE turnover in suspended rats significantly decreased in rostral A2 (48% p < 0.001), caudal A2 (52% p < 0.001) and A5 (40% p < 0.05) cell groups while it was unchanged in A1 and A6 cell groups compared with rats attached to the suspension device but maintained in the horizontal position. The short term hindlimb suspension did not alter the NE turnover in cardiac atria and ventricles or in kidneys nor did it alter the blood variables studied (hematocrit, osmolality, plasma sodium, potassium, proteins and renin concentration). We concluded that a 2.5 h hindlimb suspension reduced noradrenergic neuron activity in A2 and A5 cell groups involved in the central control of arterial pressure and particularly in the baroreceptor reflex mechanisms. This duration was probably not sufficient to modify the NE turnover in the two peripheral organs studied. PMID- 8350670 TI - Serotonin stimulates steroidogenesis in rat preovulatory follicles: involvement of 5-HT2 receptor. AB - The role of serotonin (5-HT) in the regulation of steroidogenesis in the ovary via 5-HT2 receptor was studied in normal cycling rats and their preovulatory follicles. Oral administration of ketanserin (KET), a selective 5-HT2 antagonist, at 10 mg/kg BW at 1100h on the day of proestrus resulted in a marked decrease in serum estradiol levels immediately after the administration. 5-HT stimulated estradiol secretion by preovulatory follicles incubated for 5 hrs in Krebs-Ringer bicarbonate buffer. 5-HT (2.5 microM) -enhanced estradiol secretion was inhibited by KET (1-100 microM) in a dose-dependent manner. Secretion of progesterone and testosterone was also inhibited by about the same order of magnitude as estradiol. Addition of pregnenolone (1 microgram/ml) prevented the KET-inhibited progesterone production. Both testosterone and estradiol increased at the same ratio by the addition of progesterone (1 microgram/ml). The inhibition of secretion of these hormones was overcome by dbcAMP (0.1 mM). The present study suggests that 5-HT stimulates steroidogenesis in the metabolic pathway prior to pregnenolone in rat preovulatory follicles and the action of 5-HT could possibly be mediated by a 5-HT2 receptor. PMID- 8350672 TI - Isotonic and hypertonic saline act as stressful stimuli for oxytocinergic system of the pituitary, hypothalamus and spinal cord. AB - We have recently demonstrated that immobilization stress leads to an increase in the spinal cord oxytocin content in the rat. The current experiments were undertaken to determine if other stressors have similar effect on the spinal cord oxytocin levels. Male Long Evans rats were injected either with isotonic or hypertonic saline and sacrificed either 15 minutes or 3 hours after saline injection. Oxytocin content of the neurohypophysis, hypothalamus and spinal cord were determined by specific radioimmunoassay in Sep-pak extracted samples. The results demonstrate that both isotonic and hypertonic saline act as stressful stimuli and reduce oxytocin content of the pituitary and hypothalamus when the rats were sacrificed within 15 minute following the injection. Spinal cord oxytocin content was also affected by isotonic and hypertonic saline administration; oxytocin content decreased if rats were sacrificed after a short period (15 min) and increased if rats were sacrificed after a long period (3 hours). These results, together with those reported earlier, support the hypothesis that stressors, in general, affect the spinal cord oxytocin content. PMID- 8350671 TI - Hemolytic mechanism of cytolysin produced from V. vulnificus. AB - The characteristics of hemolytic action of cytolysin produced from V. vulnificus were investigated in mouse erythrocytes. The cytolysin bound erythrocyte membranes in temperature-independent manner and then lysed cells temperature dependently. Hemoglobin release by the cytolysin was completely inhibited by the presence of raffinose or melezitose, but K+ release was not affected. The cytolysin-induced hemolysis was always accompanied with the conversion of membrane-bound cytolysin into an oligomer of 210 kDa, corresponding to a tetramer of native cytolysins. Nonesterified cholesterol inactivated the cytolysin by converting active monomeric cytolysin into inactive oligomer. The results suggest that the cytolysin lyses erythrocytes due to the formation of small pores on erythrocyte membrane by cholesterol-mediated oligomerization of the cytolysin. PMID- 8350673 TI - Chronopharmacology of amlodipine in rats. AB - The present study was undertaken to examine whether plasma concentrations of amlodipine, a calcium antagonist, and its diuretic effects vary with the time of dosage. Pharmacokinetic study; 20 mg/kg of amlodipine was given orally to rats at 10 am (day trial) or 10 pm (night trial), and blood samples were obtained during a 24-hour period. Pharmacodynamic study; two doses (10 and 20 mg/kg) of amlodipine were given orally at 10 am or 10 pm by a cross-over design, and urine was collected for 12 hours after dosage. Rats were maintained under condition of light from 7 am to 7 pm. The following results were obtained; The tmax of amlodipine was shorter and the Cmax was greater in the night trial than in the day trial. Its diuretic effects were greater in the night trial. These results suggest that the pharmacokinetic and pharmacodynamic profiles of amlodipine vary with its time of dosage. PMID- 8350674 TI - Predictability of the covalent binding of acidic drugs in man. AB - Although metabolism via glucuronide conjugation has generally been considered a detoxification route for carboxylic acids, the newly discovered chemical reactivity of these conjugates, leading to covalent binding with proteins, is consistent with the toxicity observed for drugs containing the carboxylic acid moiety. Here we report that degradation rates (intramolecular rearrangement and hydrolysis) for 9 drug glucuronide metabolites show an excellent correlation (r2 = 0.995) with the extents of drug covalent binding to albumin in vitro. Furthermore, this binding capacity is predictable based on chemical structure of the acid and depends on the degree of substitution at the carbon alpha to the carboxylic acid. The in vivo covalent binding in humans for these drugs is also predictable (r2 = 0.873) when the extent of adduct formation is corrected for the measured plasma glucuronide concentrations. These results suggest that the structure of a carboxylic acid drug may predict the degree to which the corresponding acyl glucuronides will form covalent adducts that probably/possibly lead to toxicity. This information could be a useful adjunct in drug design. PMID- 8350675 TI - In vitro hepatic thyroid hormone deiodination in iron-deficient rats: effect of dietary fat. AB - The effects of different dietary fats on thyroid indices were studied in weanling iron-deficient rats. Rats were fed one of five different diets (safflower oil with a casein protein source, safflower oil with defatted beef as the protein source, prime rib, beef tallow with casein and stearate with casein). Both dietary fat and iron status (adequate, CN; deficient, ID; or iron-deficient replete, ID-replete) had significant effects on body weight and hemoglobin concentrations. The tallow-fed animals weighed the least relative to animals fed the other fats; ID rats were smaller than CN rats. The tallow- and stearate-fed animals had the highest hemoglobin concentrations. Type of dietary fat affected plasma thyroxine (T4), but not plasma triiodothyronine (T3) or rate of deiodination of reverse T3 (rT3). Iron deficiency decreased plasma concentrations of T3 and T4 and increased in vitro hepatic rT3 deiodination, suggesting that the ID animals tend to metabolize thyroid hormones via deactivating pathways. The alterations in thyroid hormone metabolism associated with iron deficiency are reversible with iron repletion. PMID- 8350676 TI - A method for continuous blood sampling during cold water immersion. AB - A technique, consisting of a pre-calibrated, catheter-peristaltic pump combination, for continuous blood sampling was tested using six volunteers during a 20 min immersion in cold water at 14.7 +/- 0.9 degrees C. The device offered the advantage of continued collection of blood samples from an antecubital vein during the experiment with little discomfort for the subjects and in sufficient volume for assay of plasma constituents eg. catecholamines. PMID- 8350677 TI - Decreased nocturnal plasma melatonin levels in patients with recurrent acute intermittent porphyria attacks. AB - Acute intermittent porphyria (AIP) is a hereditary disease characterized biochemically by a defect in the heme pathway enzyme porphobilinogen deaminase. There is wide variability in the neurologic clinical expression of AIP, and the disorder remains latent in most gene carriers. The natural history of the disease and results in a porphyric rat model suggest a significant relationship between tryptophan metabolites and clinical expression of the disease. In the present study, we examined urine and blood tryptophan metabolite levels in AIP women before, during and after acute attacks and treatment by heme arginate. Heme arginate treatment promptly decreased total tryptophan levels (from 69 +/- 9, to 44 +/- 5, mean +/- SEM, mumole/l, p < 0.001), serotonin blood levels (from 629 +/ 103, to 356 +/- 80, nmole/l, p < 0.01) and the urinary excretion of 5-HIAA (from 3.9 +/- 0.6, to 2.2 +/- 0.4, mumole/mmole creatinine, p < 0.01). The plasma level of melatonin was found much lower than the normal control level at night (86.2 +/ 70.3, vs the normal range, 409 +/- 78.9, pmole/l +/- SEM) and day time (38.8 +/- 22.0, vs 75 +/- 13.7). Heme arginate treatment did not influence melatonin levels. Our results support the involvement of abnormal tryptophan metabolism in the pathophysiology of AIP acute attacks. Low melatonin plasma levels in porphyric women suggest that the defect of the pineal hormone may be responsible for the recurrent aspect of porphyric attacks. A desynchronization of biological rhythms in AIP patients may increase the inducibility of hepatic ALA synthase to environmental risk factors and, specially, to sex steroid hormones. PMID- 8350678 TI - EDTA-insensitive deacylation of phosphatidylinositol in porcine platelet membranes. AB - Pathways for EDTA-insensitive degradation of phosphatidylinositol (PI) were investigated in porcine platelet membranes and cytosol. The incubation of platelet membranes with [3H]glycerol-labeled PI in the presence of 2mM EDTA produced [3H]lysoPI and aqueous radioactive products, but not radioactive neutral lipids. The degradation in the membranes was optimal at pH8.0-9.0, while EDTA insensitive hydrolysis was also observed in cytosol with optimal pH at pH7.0-9.0. The major water-soluble product was identified as glycerophosphoinositol. Under the conditions, [14C]arachidonate was released from 1-stearoyl-2-[14C]arachidonyl PI without accumulation of [14C]lysoPI. The deacylation activity preferred PI to phosphatidylcholine and phosphatidylethanolamine. Collectively, these results suggest that PI can be converted to lysoPI by phospholipase A2 in the absence of free Ca2+, providing the substrates for lysoPI-specific phospholipase C characterized earlier in porcine platelet membranes (Murase and Okuyama (1985) J.Biol.Chem. 260, 262-265). PMID- 8350679 TI - Stimulation or inhibition of A431 cell growth by EGF is directly correlated with receptor tyrosine kinase concentration but not with PLC gamma activity. AB - EGF-induced hydrolysis of phosphatidylinositol 4, 5, biphosphate was compared in A431 cells with respect to their growth response to EGF. A431 cells which express 4- to 5-fold more EGF receptors than A431-4 cells were growth inhibited, while A431-4 cells were growth stimulated by EGF within the same dose range. Treatment of A431 cells with EGF resulted in a 2-fold increase in cellular IP3 levels and the effect in A431-4 cells was not as obvious. In the presence of tyrosine kinase inhibitor coumaric acid (0.2 approximately 2 microM), A431 cell growth was stimulated, rather than inhibited, by EGF in a dose-dependent manner. In contrast, the stimulation of A431-4 cell growth by EGF was reduced under the same conditions. Furthermore, in the presence of coumaric acid (up to 0.5 microM), EGF induced production of inositol phosphates in A431 cells was not obviously affected. Taken together, the results suggest that EGF-induced growth inhibition of A431 cells may be due to a quantitative changes of EGF-receptor tyrosine kinase activity in areas other than the recruitment and activation of phosphatidylinositol-specific phospholipase C gamma. PMID- 8350681 TI - Electric shock: a potentially hazardous approach to treating venomous snakebites. PMID- 8350680 TI - Cerebrospinal fluid dynorphin-converting enzyme activity is increased by voluntary exercise in the spontaneously hypertensive rat. AB - The activity in cerebrospinal fluid (CSF) of dynorphin-converting enzyme (DCE) has been studied after voluntary exercise in the spontaneously hypertensive (SH) rat. The exercise consisted of spontaneous running in wheels for 4-5 weeks and the average running distance during the last two weeks was 4.0 km/24h. CSF samples were obtained under anaesthesia from the cisterna magna after penetration of the atlanto-occipital membrane. DCE transforms the members of the dynorphin family of opioid peptides into Leu-enkephalin-Arg6. In the present investigation a radioimmunoassay was used for quantitation of Leu-enkephalin-Arg6 release from dynorphin A1-17 and dynorphin B1-13. The rats that were running had a DCE activity (vs. both substrates) in CSF that was approximately 6-12 times higher than in animals not given the running opportunity. A statistically significant correlation between the two prodynorphin-derived substrate peptides was found in terms of DCE activity. We therefore propose that a single enzyme activity may be responsible for the hydrolysis of dynorphin B1-13 and dynorphin A1-17. Furthermore, a significant correlation was also found between running activity and DCE activity 12-14 h before the CSF was withdrawn. Besides measurement of DCE activity by radioimmunoassay, the formation of Leu-enkephalin-Arg6 was identified by reversed-phase micro-column liquid chromatography and plasma desorption mass spectrometry. The experiment shows that voluntary exercise affects opioid peptidergic mechanisms. PMID- 8350682 TI - Medicine and the performing arts. PMID- 8350683 TI - Odyssey: the history of performing arts medicine. AB - The first publication to summarize the occupational diseases of musicians was Ramazzini's Diseases of Tradesmen in 1713. While there was sporadic interest in performing arts medicine during the 1800s, the first book devoted to the subject, Singer's Diseases of the Musical Profession, was published in 1932. During the 1960s and 1970s, both physicians and performers became more interested in arts medicine. When pianists Gary Graffman and Leon Fleisher publicly discussed their career-ending hand problems in the early 1980s, a huge, previously unknown group of injured musicians was brought to light. Since that time, publication in the field has dramatically increased, numerous conferences have been held, and clinics catering to the needs to performers have been set up in various large cities. Although we still do not have all the answers to the problems faced by performing artists, arts medicine is now a recognized discipline, reaching out to performers, arts educators, arts administrators, and instrument manufacturers. PMID- 8350684 TI - Upper extremity disorders in performing artists. AB - Studies in the past decade have shown that a significant proportion of instrumentalists report musculoskeletal problems severely affecting their musical performance. Musicians endure daily intensive use of their upper extremities, frequently placing them in bizarre positions. Their training schedules are rigorous and long term Predisposing factors to, and treatment for, overuse syndromes, tendinitis, and tendon trauma commonly encountered by musical performers are discussed at length. Nerve entrapment has also surfaced as a major problem in musicians, and the means of evaluation and treatment and the role of surgery are put forth. Techniques for studying and analyzing the difficulties faced by instrumentalists are summarized. PMID- 8350685 TI - Myofascial pain: the great mimicker and potentiator of other diseases in the performing artist. AB - The performing artist often sustains a variety of neuromusculoskeletal problems that interfere with the ability to play or perform. Although many of these conditions occur as a result of overuse or misuse; other causes should be kept in mind--particularly when pain problems persist, recur, or do not respond to usual therapeutic measures. Chief among these are myofascial pain syndromes. These are quite common but are often overlooked, despite the fact that they can cause, potentiate the dysfunction of, and mimic other conditions. This article presents an overview of myofascial pain and dysfunction--particularly as it pertains to neuromusculoskeletal pain and disability in musicians and performing artists. PMID- 8350686 TI - Applied ergonomics: adaptive equipment and instrument modification for musicians. AB - Failure or difficulty in treating musicians' overuse injuries is often due to overlooking aggravating roles of activities of daily living. Numerous devices are available for people with limited or painful hand function to protect joints and minimize stress of daily activities. The occupational therapist can evaluate the patient and determine which adaptations are appropriate. Instruments may be modified to render them more ergonomic and less likely to cause injuries; this is especially true for wind instruments. Biomechanically and ergonomically correct seating can minimize back and neck strain. Orthotics, such as modified chin and shoulder rests for the violin, may minimize the stress and strain of holding an instrument. Just as there is a drive to make buildings and public transportation barrier-free to the physically disabled, musical instruments can be made barrier free with adaptations like terminal devices for upper extremity prostheses. Principles of industrial and occupational medicine, especially regarding ergonomics and adaptive equipment, can be applied to the musical patient for treatment and prevention of injuries. PMID- 8350687 TI - The treatment of overuse injury syndrome. AB - The emphasis on performance injury has shifted from epidemiology to prevention. Rest treatment, modified or radical, followed by rehabilitation, remains the cornerstone of treatment. The basic features, details of management, and side effects of these treatment phases are discussed at length, followed by a detailed description of the author's experience with 176 musicians seen for overuse injury syndrome. Forty-one patients were not prescribed rest treatment, refused rest treatment, or quit rest treatment early; 45 patients were prescribed a modified rest treatment program, of whom 87% were cured of symptoms; and 90 patients were prescribed radical rest treatment, with a final success rate of 87% also. PMID- 8350688 TI - Addressing stress-related illness in professional musicians. AB - The health profession has become increasingly aware of the frequent incidence of work-related injuries and illnesses occurring among professional musicians. Although all workers run risks of stress-related health problems, performers must work under especially stressful conditions. Musicians must perform before the public; they must perform under the constant critical scrutiny of conductors; and they are expected to perform perfectly. Stressors, some unique to the music profession, some shared with other working populations, can come from the environment in which musicians must work, from psychological pressures, and from factors intrinsic to a performing career. In response to the increasing incidence and awareness of the health problems of professional musicians, music medicine, a new medical specialty, has come into being. Physicians who treat performers can act as resources to educate their patients about work-related stress and to refer them to appropriate mental health professionals. They can be instrumental in helping musician patients return to performing careers with a new ability to handle work-related injuries and stress. PMID- 8350689 TI - Life in the orchestra. AB - The concert soloist and conductor are prominent figures within the orchestra. Their roles make extraordinary demands on them--demands that must often be fulfilled while dealing with the problems of travel. Maintaining one's skill is a constant concern. The orchestra musician is also constantly on guard to maintain performance excellence. Unusual work patterns, obsession with the job, and job stress can put pressure on home life. The strong emotional personality of the orchestra musician must adapt to the conductor's desires and musical tradition. The player must coordinate performance with other group members. Other factors contribute to an environment with rigid boundaries and to the isolation of orchestra members as a group. With the development of performing arts medicine, injuries are less stigmatized and better treated, and performance stress is better managed. A patient's view of medicine is offered here. PMID- 8350690 TI - Consent to treatment: application to performing arts medicine. AB - Because treatment outcomes may have an effect on performing artists' livelihood, physicians should involve these patients in the treatment planning phase by obtaining informed consent. Treatment without consent is a battery. Physicians have several available lines of defense against an allegation of failure to obtain informed consent, including reasonable documentation of treatment plan discussions with patients; the "so what!" defense, which states that the patient would have agreed to treatment despite the risks; and the "unduly alarming" defense, which contends that based on past experience with a particular patient, proper disclosure would cause undue emotional distress. Alert compliance with the laws governing consent for treatment and sound medical judgment are every physicians' legal, ethical, and moral duty. PMID- 8350691 TI - Foot care for the patient with diabetes. PMID- 8350692 TI - Imaging case of the month. Tuberculous osteomyelitis, discitis, and epidural abscess. PMID- 8350693 TI - Treatment of panic disorder: summary of the NIH consensus statement. PMID- 8350694 TI - Panic disorder: a commentary. PMID- 8350695 TI - Epidemiology & Disease Control Program. March, 1993. Tips for vaccine administration. PMID- 8350697 TI - The female athlete triad: disordered eating, amenorrhea, osteoporosis. PMID- 8350696 TI - Mitochondrial DNA sequence polymorphism, VO2max, and response to endurance training. AB - Mitochondrial DNA sequence variation was determined in 46 sedentary young adult males who took part in ergocycle endurance training programs in two laboratories to assess whether mitochondrial DNA variants were associated with individual differences in maximal oxygen uptake (VO2max) and its response to training. VO2max was obtained from a progressive ergocycle test to exhaustion. White blood cell mitochondrial DNA was characterized with the restriction fragment length polymorphism (RFLP) technique using 22 restriction enzymes and human mitochondrial DNA as a probe for hybridization. Multiple mitochondrial DNA variants were detected with 15 of the enzymes. Some subjects exhibited many RFLPs, while others showed no variation. These RFLPs (morphs) were generated by base substitutions located in gene regions coding for mitochondrial proteins as well as in the noncoding regions. Carriers of three mitochondrial DNA morphs, two in the subunit 5 of the NADH dehydrogenase gene and one in the tRNA for threonine, had a VO2max (ml.kg-1.min-1) in the untrained state significantly higher than noncarriers, while carriers of one mitochondrial DNA morph in subunit 2 of NADH dehydrogenase had a lower initial VO2max. Endurance training increased VO2max by a mean of 0.5 l of O2, with individual differences ranging from gains of 0.06 to 1.03. After adjustment for training site and initial VO2max, a lower response was observed for three carriers of a variant in subunit 5 of the NADH dehydrogenase detected with HincII (mean gain of 0.28 l; P < 0.05). These results suggest that sequence variation in mitochondrial DNA may contribute to individual difference in VO2max and its response to training. PMID- 8350698 TI - The effect of intense interval exercise on iron status parameters in trained men. AB - Iron and iron-binding proteins play a critical role in the physiology of many human systems, including the immune system. Intense interval exercise in trained men (mean [SD] age = 31.5 [4.5] yr; VO2max = 64.3 [3.8] ml.kg-1.min-1) is associated with significant modulation of iron status parameters. The concentration of red blood cells, hemoglobin, and transferrin all increased significantly immediately post-test (P < 0.01), increases which can largely be attributed to hemoconcentration. Serum iron was elevated by approximately 25% both immediately and 1 h post-test (P < 0.08). Maximum post-test serum iron values (either immediately or 1 h post-test) were significantly elevated with respect to rest (P < 0.01). Transferrin concentration was also significantly elevated at 24 h post-test (P < 0.05). Transferrin saturation was not significantly altered by this protocol (P > 0.10). Despite a trend toward elevation at 24 h post-test, ferritin concentration was not significantly different from the resting value at any sampling point. Intense interval exercise appears to be associated with significant modulation of iron status, the biological importance of which remains to be determined. PMID- 8350699 TI - Fatigability of human quadriceps femoris muscle following anterior cruciate ligament reconstruction. AB - The responses of quadriceps femoris muscles to an electrically elicited fatigue test were recorded from both lower extremities of 18 patients who had recently undergone unilateral, anterior cruciate ligament reconstruction. The fatigue test consisted of 40 pps, 13-pulse electrical trains that were repeated once per second for 3 min. The intensity of stimulation was set for each extremity to produce 20% of the maximum voluntary isometric contraction of the uninvolved muscle. The uninvolved quadriceps femoris muscle showed a significantly greater rate of decline in force over the first minute than the involved muscle (0.803%.s 1 for uninvolved muscle vs 0.620%.s-1 for involved muscle). Similarly, the average forces produced over the last minute were significantly lower for the uninvolved than the involved quadriceps femoris muscle (uninvolved = 42.6%, involved = 50.4% of their original forces). These surprising results showed that the involved quadriceps femoris muscles were more endurant than the uninvolved muscles. It is suggested that the increases in endurance of the involved muscle may have been due, in part, to greater recruitment of Type I fibers with electrical stimulation or selective Type II fiber atrophy in the involved muscle. PMID- 8350701 TI - Iron status and diet in athletes. AB - Plasma ferritin (F) concentrations were measured (range 12-245 ng.ml-1) as an indicator of iron status in 24 male and 45 female healthy, nonanemic athletes. Usual food intake was assessed using a self-completed but supervised food frequency questionnaire. Linear regression was applied to determine the relationship between log F (as data was skewed) and average daily intake of iron (Fe), meat (M), protein (Pr), carbohydrate (CHO), fat (Fa), fiber (Fi), and kilojoules (Kj). There were negative correlations between F and each of Kj (P < 0.01) and CHO (P < 0.001), and a positive correlation between F and Pr/Kj (P < 0.01). No significant relationship existed between F and any of Fe, M, Fa, or Fi. These data suggest that iron or meat intake may not be important determinants of iron status in these athletes. Instead, the percentage of protein in the diet may be more influential on F, as may the (negative) effect of Kj and CHO intake, or at least their reflection of energy expenditure. PMID- 8350700 TI - Physiologic responses to shoveling and thermal stress in men with cardiac disease. AB - To investigate the effect of temperature stress on responses to static-dynamic work in patients with ischemic heart disease (IHD), 10 men with IHD shoveled gravel for 30 min in a warm (29 degrees C), neutral (24 degrees C), and cold (-8 degrees C) environment (on separate days). A pace of 15 lifts.min-1 was set, and the load per lift approximated 5.5 kg. Heart rate (HR), oxygen consumption (VO2), and systolic (SBP) and diastolic blood pressures (DBP) were evaluated at 5-min intervals. Arrhythmias and ST-segment depression were evaluated by ambulatory electrocardiographic monitoring. At 30 min, VO2, SBP, and DBP were higher (P < 0.05) in the cold environment, and HR was higher (P < 0.05) in the warm environment compared with the neutral environment. HR increased (P < 0.05) from 5 to 30 min in all three conditions. The increase in HR was greater (P < 0.05) in the warm environment. None of the subjects reported angina or demonstrated electrocardiographic ST-segment changes during shoveling in any environment. The results indicate that low-risk patients with stable IHD show modest temperature induced alterations in hemodynamic and VO2 responses during 30 min of moderate intensity (50-60% of peak VO2) static-dynamic work without adverse electrocardiographic responses or symptomatology. PMID- 8350702 TI - Fractures, physical activity, and growth velocity in adolescent Belgian boys. AB - The relationship of fractures to physical activity and growth velocity in stature and metacarpal II bone dimensions was investigated in adolescent Belgian boys. Peak fracture incidence occurred between 12 and 14 yr of age and preceded the age at peak height velocity. The peak fracture rate occurred during mid adolescence (+/- 2 SD of the age at peak height velocity) and was twice as high as the rates before and after this period. The majority of fractures occurred during active participation in sports and general physical activities. The age at peak growth velocity for metacarpal cortical thickness, an indirect measure of bone mineral content, was about 6 months later than the ages at peak height velocity and peak growth velocity for metacarpal length. Peak fracture incidence occurred during a period when the amount of time spent in sports physical activity was low compared with later years. A lag in cortical bone thickness and mineralization, relative to linear skeletal growth, and unknown factors associated with active participation in sports, rather than an increase in the amount of physical activity, appear to be the predominant factors associated with the increased fracture incidence in Belgian boys during the growth spurt. PMID- 8350703 TI - Effects of prior exercise or ammonium chloride ingestion on muscular strength and endurance. AB - Previous studies linked muscular fatigue with a decrease in blood pH. This study investigated if the means of altering pH affected the extent of muscular fatigue. Drug-induced and exercise-induced acidosis were compared to test the hypothesis that exercise-induced acidosis impairs subsequent muscular performance more than chemically induced acidosis. In eight male subjects acidosis was induced by ingesting 0.3 g.kg-1 ammonium chloride (AC) for one trial, by upper body exercise (UBE) for another trial, and after placebo (PL) treatment. They then completed a performance test (PT) of 50 maximal, bilateral isokinetic knee extensions. Whole blood pH before (pHpre) and after (pHpost) the PT was 7.412, 7.264, and 7.261 for PL, UBE, and AC, respectively; both AC and UBE decreased pH similarly compared with PL. Peak torque and total work during the PT were similar for PL and AC, and were significantly greater than after UBE. Six subjects performed a fourth trial after combined AC and UBE treatments causing a pHpre of 7.081, but there was no greater performance impairment than that caused by UBE alone. The results dissociate the extent of the impairment from the magnitude of the disruption in blood pH. PMID- 8350705 TI - Physical activity and immune function in elderly women. AB - The relationship between cardiorespiratory exercise, immune function, and upper respiratory tract infection (URTI) was studied in elderly women utilizing a randomized controlled experimental design with a follow-up of 12 wk. Thirty-two sedentary, elderly Caucasian women, 67-85 yr of age, who met specific selection criteria, were randomized to either a walking or calisthenic group; 30 completed the study. Twelve highly conditioned elderly women, 65-84 yr of age, who were active in endurance competitions, were recruited at baseline for cross-sectional comparisons. Intervention groups exercised 30-40 min, 5 d.wk-1, for 12 wk, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. At baseline, the highly conditioned subjects exhibited superior NK (119 +/- 13 vs 77 +/- 8 lytic units, P < 0.01) and T (33.3 +/- 4.9 vs 21.4 +/- 2.1 cpm x 10(-3) using PHA, P < 0.05) cell function, despite no differences in circulating levels of lymphocyte subpopulations. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6%, but did not result in any improvement in NK cell activity or T cell function. Incidence of URTI was lowest in the highly conditioned group and highest in the calisthenic control group during the 12-wk study, with the walkers in an intermediate position (chi-square = 6.36, P = 0.042). In conclusion, the highly conditioned elderly women in this study had superior NK and T cell function when compared with their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350704 TI - Effect of training and anabolic-androgenic steroids on drug metabolism in rat liver. AB - The effects of anabolic-androgenic steroid administration and exercise training on various aspects of hepatic function were investigated in sedentary and trained (treadmill for 12 wk) male and female rats treated orally with fluoxymesterone or methylandrostanolone (2 mg.kg-1 body weight, 5 d.wk-1 for 8 wk). The mean values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, and total- and high-density lipoprotein cholesterol remained within normal range in all groups of male animals. The same is true for female rats, except for an increase in alkaline phosphatase activity in the steroid-treated groups. Hepatic microsomal aniline p-hydroxylase activity was reduced in male and increased in female rats by either steroid, whereas no significant effect was detected on 7-ethoxycoumarin deethylase activity. The levels of cytochrome P-450 and cytochrome b5 were markedly decreased by the anabolic-androgenic steroid treatment in male rat microsomes, but neither the steroid administration nor exercise training induced significant changes in the cytochrome levels of female rat livers. Taking into account the significant increase in microsomal protein yield elicited by fluoxymesterone or methylandrostanolone treatment both in males and females, it is noteworthy that the total monooxygenase activities and cytochrome P-450 content, expressed on a per gram liver basis, were significantly increased in female whereas they were apparently unchanged in male rats. In conclusion, the present data show that the prolonged ingestion of high doses of anabolic-androgenic steroids, either with or without concurrent exercise training, can modify in a sex-dependent manner the capacity of rat liver to metabolize drugs without affecting classical serum indicators of hepatic function. PMID- 8350706 TI - Changes of vinculin and extracellular matrix components following blunt trauma to rat skeletal muscle. AB - The purpose of the present study was to determine changes in the localization of vinculin, Type IV collagen, laminin, and fibronectin during the damage-repair process in the skeletal muscle over several days following acute blunt trauma. A single blunt trauma to the gastrocnemius muscle of the rat was induced by applying 1.57 J of kinetic energy to one leg. By day 2 after trauma, vinculin had disappeared rapidly from the intracellular submembraneous region corresponding to the costamere, whereas Type IV collagen and laminin persisted around the degenerating myofibers (corresponding to the basement membrane). Fibronectin could be observed filling the widened endomysium and in the ruptured myofibers. In the early phase of muscle regeneration (day 5 after trauma), newly synthesized vinculin, Type IV collagen, and laminin formed ring-like structures around the regenerating myotubes. Fibronectin could also be observed filling the widened endomysium around the regenerating myotubes. Further, when small newly formed or splitted myofibers were observed in the areas of regenerating myofibers (day 10 after trauma), vinculin, Type IV collagen, laminin, and fibronectin were localized in specialized regions corresponding to the costamere, basement membrane, and endomysium. These results demonstrated that restoration of the costamere, basement membrane, and endomysium are essential to the maturation of regenerating myofibers after injury. PMID- 8350707 TI - Training effects on maternal and fetal glucose uptake following acute exercise in the rat. AB - The purpose of the present study was to determine the effects of chronic maternal exercise on glucose uptake in maternal tissues after one bout of treadmill running during late gestation in the rat and to determine the effects on glucose accumulation in the fetus and placenta. Trained pregnant animals (PR) ran at 30 m.min-1, on a 10 degrees incline for 1 h on day 20 of gestation with a similarly treated trained nonpregnant group (NPR). Immediately after the run the animals were infused with a bolus of 1 g.kg-1 body wt as a 50% dextrose solution mixed with 2-deoxy-D-[1-3H] glucose through a carotid catheter. Sedentary pregnant (P) and nonpregnant animals (C) were also infused with the solution after no food and water for the same time frame. After 60 min, tissues were analyzed for radioactivity. Radioactive tracer was augmented in the red gastrocnemius and soleus of the PR group and the soleus of P rats. However, tracer accumulation in the fetus and placenta of the trained animals was not different than P animals. These results indicate that acute exercise in trained animals increased glucose uptake in maternal skeletal muscles without compromising conceptus glucose accumulation. PMID- 8350709 TI - Overtraining in endurance athletes: a brief review. AB - Overtraining is an imbalance between training and recovery, exercise and exercise capacity, stress and stress tolerance. Stress is the sum of training and nontraining stress factors. Peripheral (short-term overtraining, STO) or peripheral and central fatigue may result (long-term overtraining, LTO). STO lasting a few days up to 2 wk is termed overreaching. STO is associated with fatigue, reduction, or stagnation of the 4 LT performance capacity (performance at 4 mmol lactate or comparable criterion), reduction of maximum performance capacity, and brief competitive incompetence. Recovery is achieved within days, so the prognosis is favorable. LTO lasting weeks or months causes overtraining syndrome or staleness. The symptomatology associated with overtraining syndrome has changed over the last 50 yr from excitation and restlessness (so-called sympathetic form) to phlegmatic behavior and inhibition (so-called parasympathetic form). Increased volume of training at a high-intensity level is likely the culprit. The parasympathetic form of overtraining syndrome dominates in endurance sports. Accumulation of exercise and nonexercise fatigue, stagnation, or reduction of the 4 LT performance capacity, reduction in maximum performance capacity, mood state disturbances, muscle soreness/stiffness, and long-term competitive incompetence can be expected. Complete recovery requires weeks and months, so the prognosis is unfavorable. Other optional or further confirmation requiring findings include changes in blood chemistry variables, hormone levels, and nocturnal urinary catecholamine excretion. Based on the findings reported, recommendations for training monitoring can be made, but their relevance in the practice must still be clarified. PMID- 8350708 TI - The epidemiology of leisure physical activity in an adolescent population. AB - A cohort of 1245 adolescents, 12-16 yr old and participating in a prospective study of risk factors for injury, were surveyed annually to assess past year leisure physical activity. This report describes the development and reproducibility of the questionnaire and provides the descriptive epidemiology of leisure physical activity in adolescents. The questionnaire was self-administered twice, a year apart, and had a 1 yr test-retest rank order correlation of 0.55. The past year estimate of leisure activity was also shown to be related to fitness (rho = -0.37), which was defined as the time needed to complete a 1-mile run. Males reported significantly more activity than females (P < 0.05) and whites reported more activity than nonwhites (P < 0.05). However, socioeconomic status was not found to be a determinant of activity levels in either males or females. In females, a negative association between activity and age was found (P < 0.05); however, this association was not evident in males. In summary, an activity questionnaire has been developed and was shown to be both reproducible and feasible. Therefore, it was used to examine habitual leisure physical activity patterns of adolescents. PMID- 8350710 TI - Isometric strength, sprint power, and aerobic power in individuals with a spinal cord injury. AB - This study investigated in rather specific wheelchair tests the relationships among estimates of isometric upper-body strength (Fiso), sprint power (P30), aerobic power (VO2peak), and maximal power output (POaer) in a group of 44 men (age 34 +/- 12 yr) with longstanding spinal cord injuries ranging from C4/C5 to L5. Fiso was defined as the maximum force that could be exerted on the blocked rims of a stationary wheelchair ergometer. The estimation of P30 involved the measurement of the mean power during a 30-s all-out sprint test on the same wheelchair ergometer. VO2peak and POaer were determined as the peak oxygen uptake and highest sustained power output during a discontinuous progressive maximal exercise test on a motorized treadmill, while subjects used their own daily use wheelchair. Fiso ranged from 1.5 N.kg-1 (mean of both arms) in the group with quadriplegia to 3.4 N.kg-1 in the group with lowest-lesions, and P30 ranged from 0.5 to 1.5 W.kg-1 among the subjects. VO2peak ranged from 13.6 ml.kg-1.min-1 in the group with quadriplegia to 31.3 ml.kg-1.min-1 in the group with lowest lesions, and POaer ranged from 0.4 to 1.1 W.kg-1. Strong positive relationships (r = 0.81-0.92) were demonstrated among all variables. Regression equations among variables were calculated: P30 = 0.51 Fiso - 0.18 (R2 = 0.75); POaer = 0.34 Fiso 0.02 (R2 = 0.66); POaer = 0.67 P30 + 0.11 (R2 = 0.81); VO2peak = 6.52 Fiso + 4.15 (R2 = 0.76); VO2peak = 12.03 P30 + 7.43 (R2 = 0.77); VO2peak = 16.81 POaer + 6.44 (R2 = 0.84).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350711 TI - Physiological predictors of short-course triathlon performance. AB - The purpose of this study was to investigate if selected physiological variables were related to triathlon performance. Eighteen male and seven female triathletes competed in a short-course triathlon (1-km swim, 30-km cycle, 9-km run) and underwent physiological testing within 14 d. VO2max and ventilatory threshold (VT) were measured on a cycle ergometer, treadmill, and tethered swim apparatus. Leg flexion and extension strength were measured on a Cybex II isokinetic dynamometer. Multiple linear regression did not improve the prediction of triathlon performance over that provided by simple correlations. Swim performance was related to relative swim VO2max in both males (r = -0.48) and females (r = 0.93) as well as the resistance pulled at swim VT (r = -0.81) and absolute leg flexion strength (r = -0.77) in females. No physiological variables were significantly related to cycling time in either gender. Running time was related to relative VO2max (r = -0.88) in females and velocity at run VT in both females (r = -0.88) and males (r = -0.73). Relative swim VO2max (r = -0.98), velocity at run VT (r = -0.89), and absolute leg flexion strength (r = -0.80) were related to overall performance in female triathletes. The only significant predictor of overall triathlon time for males was velocity at run VT (r = -0.78). It therefore appears that in short-course triathletes physiological variables in swimming and running are important to overall performance. Differences in sample size, group variability, and level of performance between males and females may account for the reported differences in the physiological predictors of performance between genders. PMID- 8350712 TI - Physiological responses during simulated competition. AB - Laboratory studies with competitive athletes often use graded exercise protocols to elicit physiologic responses. This pattern of power output is different than ordinarily employed by athletes during competition. To understand the physiologic responses during competition, we studied 24 athletes (speed skaters, cyclists, triathletes) during simulated competition, a 5-km time trial on a racing bicycle attached to a windload simulator, and during cycle ergometer graded exercise testing (N = 8). During the time trial the velocity pattern was similar to real world competitions, and the subjects indicated that the time trial was perceptually similar to competition. Physiologic responses were of significantly greater magnitude vs graded exercise (VO2max: 3.46 +/- 0.73 vs 3.27 +/- 0.79 l.min-1; VEmax: 138 +/- 27 vs 119 +/- 22 l.min-1; HRmax 184 +/- 11 vs 175 +/- 11 beats x min-1; HLa 14.8 +/- 3.7 vs 11.9 +/- 2.1 mM). All physiologic measures increased steadily throughout the time trial (km 0, 1, 2, 3, 4, and 5: VO2 = 1.03, 2.95, 3.42, 3.69, 3.82, and 3.92 l.min-1; HR = 93, 175, 181, 185, 189, and 194 beats.min-1; VE = 31, 99, 120, 129, 145, and 156 l.min-1; HLa = 2.9, 5.6, 7.2, 9.2, 10.6, and 13.5 mM). In six subjects (speed skaters), the peak values observed during time trial for HR (188 +/- 6 vs 191 +/- 5 beats.min-1) and HLa (16.4 +/- 3.1 vs 17.0 +/- 4.2 mM) were not significantly different than observed during real world competition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350713 TI - Tilt table testing in the evaluation and management of athletes with recurrent exercise-induced syncope. PMID- 8350714 TI - Metabolic changes in the rat brain after acute and chronic ethanol intoxication: a 31P NMR spectroscopy study. AB - In this work, 31P phosphorus NMR (31P NMR) studies of the brain have been conducted in rats acutely and chronically intoxicated with ethanol. In both groups, changes in levels of high-energy phosphates were observed: increase of phosphocreatinine (PCr)/beta AaTP and PCr/inorganic phosphate (Pi) in acute and long-term ethanol exposure, and decrease of Pi/beta ATP after acute ethanol administration. These changes in high-energy phosphates, indicative of a reduction of adenosine triphosphate (ATP) and PCr consumption (PCr+ ADP+ H+ ATP+ Cr; ATP ADP+ Pi), suggest a reduction of cerebral metabolism both in acute and chronic ethanol exposure. In addition, in the group of rats chronically intoxicated with ethanol, there were variations in phosphodiester peak intensities (decrease of phosphomonoester (PME)/phosphodiester (PDE), increase of PDE/beta ATP), suggesting increased breakdown of membrane phospholipids. These changes could provide a metabolic explanation for the development of cerebral atrophy in chronic alcoholism. PMID- 8350715 TI - Resolution of phospholipid molecular species by 31P NMR. AB - Phosphorus-31 NMR chemical shifts of phospholipids (PLs) solubilized in bile salts were studied with respect to variations in the structure of the acyl substituents. The presence of double bonds in the acyl chains of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and phosphatidic acid (PA) induced small but consistent upfield shifts relative to the corresponding disaturated acyl PL signals. The magnitudes of the unsaturation-related upfield shifts were approximately twice as large in sodium cholate as in sodium deoxycholate. Chemical shift separations of PC, PE, and PG dipalmitoyl-dioleoyl species pairs increased slightly at lower temperatures. Resolution of the PC species pair was maximized and nearly independent of cholate to-PL ratio at values greater than about 100 in 2% cholate. Only the PA species resolution varied significantly over the pH range 6.5 to 9.5, in the vicinity of its pK2. Shift differences for a homologous series of disaturated acyl PCs showed a logarithmic dependence on chain length. Spectra for a variety of PC standards were used to interpret the composite PC signals from egg yolk extract, soybean extract and whole human amniotic fluid. The 31P NMR analyses were consistent with published chromatographic studies. Interpretation of composite PL signals in the cholate system is simplified for mixtures having restricted acyl chain length and degree of unsaturation. PMID- 8350716 TI - The proton NMR spectrum in acute EAE: the significance of the change in the Cho:Cr ratio. AB - We have studied by nuclear magnetic resonance spectroscopy the evolution of the proton spectral changes in acute experimental allergic encephalomyelitis. We found an in vivo elevation in the ratio between the peaks assigned to "choline containing compounds" (Cho) and creatine plus phosphocreatine (Cr). This was associated with an increase in choline, betaine, and phosphorylcholine (PC) as well as a reduction in N-acetylaspartate (NAA), aspartate, N acetylaspartatylglutamate and inositol in vitro. Histological examination revealed inflammation with no evidence of demyelination or neuronal loss. We conclude that the increase in the ratio of Cho:Cr was due to an increase in the concentrations of PC, betaine, and choline in association with inflammation, and not as others have suggested, with demyelination. The reported reduction in NAA may be due to dysfunction of neurones rather than their loss. PMID- 8350717 TI - Limits to neural stimulation in echo-planar imaging. AB - Simple electrical circuits are used to model neural stimulation. The stimulation current is evaluated for a variety of magnetically induced waveforms and for sinusoidal stimulation as a function of frequency. Experimental results obtained using a small scale magnetic stimulator show that the transient response rather than the steady-state behavior determines the stimulation characteristics thus suggesting a nonlinear model. We show that a nonlinear circuit changes a steady state current solution into a repeated transient solution and thereby better explains our experimental results. Our model also shows that for very short times and high frequencies, contrary to the current widely held view, neural stimulation is independent of the magnetic field switching rate dB/dt, but depends on the final magnetic field value, Bm. At lower frequencies and rise times, there may be a small advantage in using square wave over sine wave gradient modulation for whole body echo-planar imaging (EPI). It is found that the peak stimulation fields Bm, for both sinusoidal and trapezoidal waveforms are equal for equal risetimes. This means that for a given image array size and imaging time, trapezoidal modulation EPI ultimately can be made to operate below the neural triggering threshold while the equivalent sine modulation EPI version transcends the threshold. PMID- 8350718 TI - Quantitative interpretation of magnetization transfer. AB - Magnetization transfer contrast (MTC) experiments using off-resonance irradiation have been performed with an agar gel model by systematically varying offset frequency, amplitude of the RF irradiation and gel concentration. The experimental results are shown to be quantitatively modelled by a two-pool system consisting of a liquid pool with a Lorentzian line shape and a small semisolid pool with a Gaussian lineshape. The fitted model yields physically realistic fundamental parameters with a T2 of the semisolid pool of 13 microseconds. Further analysis shows that the off-resonance irradiation MTC experiment had significant limitations in its ability to saturate the semisolid pool without directly affecting the liquid component. PMID- 8350719 TI - Spin-spin relaxation in experimental allergic encephalomyelitis. Analysis of CPMG data using a non-linear least squares method and linear inverse theory. AB - We have used the CPMG pulse sequence to measure proton T2 values and water content in spinal cord and brain samples from Hartley guinea pigs inoculated to produce experimental allergic encephalomyelitis (EAE). Relaxation data were fitted using minuit, a non-linear curve fitting routine. Three exponentials provided the best fit to spinal cord data (10 ms (13%), 76 ms (57%), 215 ms (30%)) and two exponentials for brain tissue (10 ms (4%), 92 ms (96%)). Least squares algorithms were also used to analyse the spinal cord data in terms of discrete and smooth distributions of relaxation times. The discrete least squares solutions consisted of three to five isolated spikes between 0.010 and 0.300 s. This type of solution was difficult to interpret in terms of water reservoirs. Smooth solutions consisted of two broad peaks, a small peak with a T2 near 0.010 s and a larger peak near 0.100 s. The integral ratio of the larger to the smaller peak was 7.092 +/- 1.782 for normal tissue, and increased to a maximum of 16 with increasing parenchymal cellular infiltration and demyelination. The short T2 peak has been assigned to water in the hydration layers of the myelin sheath. The width of the longer T2 peak was sensitive to tissue heterogeneity. The least squares and smooth distribution analysis models could be used to distinguish samples with extensive parenchymal infiltration from normal tissue, even though only a maximum of 60% of the tissue was affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350720 TI - Echo-planar spin-echo and inversion pulses. AB - The echo-planar k-space trajectory can be used as the basis for any two dimensional selective pulse. The main application is spectral-spatial pulses, which must be based on the echo-planar trajectory. In this paper we show how echo planar spin-echo (EPSE) pulses may be designed. PMID- 8350721 TI - An asymmetric slice profile: spatial alteration of flow signal response in 3D time-of-flight NMR angiography. AB - We introduce an asymmetric slice profile technique, which alters the spatial response of the flow signal in 3D time-of-flight NMR angiography. By gradually increasing the flip angle from the inflow to the outflow portions of the slab, the inflow refreshment effect is distributed over a wide slab thickness. The asymmetric slice profile is simply produced by using a Gaussian RF excitation with an overlapping presaturation. The spatial distribution of steady flow signal in a phantom study demonstrated an essential agreement with a numerical simulation. 3D time-of-flight NMR angiography of volunteers' heads using this technique provided a smooth vascular depiction over a wide slab thickness. PMID- 8350722 TI - Blood flow measurement using variable velocity encoding in the RR interval. AB - Velocity-encoded phase imaging using asynchronous gating requires input of a velocity encoding value to set the velocity sensitivity of the pulse sequence. The raw data interpolation and reconstruction scheme that the pulse sequence uses forces the encoding value to be constant throughout the RR interval. The sequence and the raw data interpolation scheme were modified to allow two velocity encodings during the RR interval. Two-hundred cm/s encoding was used in systole, and 30 cm/s in diastole. Changing the encoding in diastole significantly improved the accuracy and precision of ascending aorta flow measurements. PMID- 8350724 TI - Automatic, localized in vivo adjustment of all first- and second-order shim coils. AB - The implementation of a "fast, automatic shimming technique by mapping along projections" (FASTMAP) on a 2.1-Tesla whole-body system is described. The method provides a localized adjustment of all first- (X, Y, Z) and second-order (Z2, ZX, ZY, X2-Y2, 2XY) coils in 2 min. The time savings are achieved by mapping the magnetic field along six projections rather than from whole-imaging data sets. An analysis of noise error propagation suggests that in 64-ml volumes the residual linewidths obtained with the method are negligible when the signal-to-rms-noise ratio is above 30. The initial application of the method to localized 13C, 31P, and 1H spectroscopy of the human brain resulted in linewidths of approximately 2 Hz for 13C (144-ml volume), approximately 2.5 Hz for 31P (36-ml volume) and approximately 4 Hz for 1H (36-ml volume) with symmetric and reproducible lineshapes. PMID- 8350723 TI - Nonaxial whole-body instant imaging. AB - We demonstrate that whole-body, single-shot imaging is practical for imaging out of the central plane, including oblique axes. The technique is illustrated by images of the heart in the cardiac long- and short-axis and by coronal images of the brain. Secondary gradients can produce additional image distortion and ghosting in these images. These artifacts are a direct consequence, predictable by Maxwell's equations, of the large gradients used in echo planar imaging. We show that these effects are, in general, made smaller by working at a high magnetic field. PMID- 8350725 TI - Nonmagnetic hyperbaric chamber for in vivo NMR spectroscopy studies of small animals. AB - A description is given of the design, construction, and initial use of a polycarbonate resin hyperbaric chamber for in vivo NMR spectroscopy studies of anesthetized, ventilated rats in a horizontal bore 4.7 Tesla magnet. The chamber and its associated equipment, initially used for hyperbaric studies of rats in states of extreme hypercapnia, are also well suited for conventional hyperbaric studies, such as those related to hyperbaric oxygen therapy, oxygen toxicity, and diving. Basic technical challenges that required innovations involved: a) preservation of magnetic field homogeneity; b) avoidance of a metallic chamber body that would overload gradient and RF coils; c) physiological monitoring; and, d) remote control and stabilization of electromagnetic and physiologic factors (especially ventilatory stability) during pressure changes. A small paramagnetic bulk magnetic susceptibility shift from chamber-associated hyperbaric oxygen was observed when chamber oxygen tensions were only one atmosphere. High-quality NMR imaging and spectroscopy were demonstrated during hyperbaric conditions. PMID- 8350726 TI - Gadolinium-DTPA enhanced MRI demonstrates uterine vascular changes associated with artificially induced decidualization and ovoimplantation in rats. AB - Gadolinium-DTPA enhanced magnetic resonance (MR) imaging has been used to demonstrate uterine vascular changes during ovoimplantation and artificially induced decidualization in rats. Evans blue dye and Gd-DTPA were injected i.v. into rats 10 h after unilateral decidualization was induced by injection of sesame oil into the lumen of one uterine horn. Animals were killed various times later and uteri were removed, T1-weighted proton imaging was performed, and mean image intensities for stimulated and control uterine horns were calculated by computer-assisted image analysis. Macroscopic bluing confined to stimulated horns was apparent 5 min after tracer injection and increased in intensity until the experiment was terminated at 320 min. Analysis of MR images showed that mean image intensity of control horns did not change significantly at any time after injection of the Gd-DTPA and Evans blue whereas mean image intensity of stimulated horns increased significantly by 5 min after injection, peaked at 20 min, and returned to values not different from controls by 320 min. T1-weighted images of day 6 pregnant rats injected with Gd-DTPA and Evans blue revealed patterns of image enhancement that matched those of macroscopic bluing. Uterine concentrations of radioactivity after injection of 153Gd-DTPA indicated that increased extracellular fluid volume (ECFV) produces the image enhancement of stimulated horns since the tracer permeates the extracellular fluid of both horns. Gd-DTPA-enhanced MR imaging of uteri after deciduogenic stimulation revealed significant image enhancement for stimulated horns at both 9 and 27 h after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350727 TI - Spatially localized 31P NMR measurements of longitudinal relaxation rates in the canine myocardium. AB - FLAX-ISIS spatial localization was combined with inversion recovery to enable the measurement of spatially localized T1 values. This approach was applied to the transmural determination of creatine phosphate longitudinal relaxation times in the canine myocardium. By examining five voxels spanning the left myocardial wall, we observed that transmural T1 values for creatine phosphate ranged from 3.61 +/- 0.20 in the endocardium to 4.00 +/- 0.20 in the epicardium at 4.7 Tesla. As such, the canine myocardium exhibits no transmural variation in the T1 values of creatine phosphate. This simple approach can be extended to enable the in vivo measurement of transmural enzymatic rates. PMID- 8350728 TI - Stability and nonreactivity of ergothioneine in human erythrocytes studied by 1H NMR. AB - The N(CH3)3 resonance of ergothioneine in 1H spin-echo Fourier transform (SEFT) NMR spectra of red blood cells is usually a large singlet and it has been common practice to use this apparently unchanging resonance as an intensity reference. Recently, Reglinski et al. (Magn. Reson. Med. 6, 217-223 (1988)) have questioned this practice, reporting changes seen in the resonance in response to oxidative stress induced by arsenicals. We propose that the changes in the ergothioneine resonance that were reported are artifacts due to alterations in osmolality and magnetic susceptibility induced by the addition of nonisotonic solutions to red blood cell suspensions. These factors change the specific intensity of the intracellular resonances of all compounds. Ergothioneine was observed not to take part in any chemical reactions with arsenicals in free solution or in intact erythrocytes, and we conclude that ergothioneine may still be used as an internal intensity reference in 1H SEFT NMR spectra, bearing in mind the above physical factors. PMID- 8350729 TI - K-space substitution: a novel dynamic imaging technique. AB - A rapid dynamic imaging sequence has been developed in which only the 32 phase encoding steps that encode low spatial frequencies are collected for each dynamic image. These are substituted into a previously acquired, 128 x 128 raw data set prior to image reconstruction. In this way the dynamic information is retained while the overall appearance is improved in comparison with images obtained by zero filling to 128 x 128, leading to better qualitative evaluation. The limited k-space sampling means that the technique is most effective for large homogeneous areas of signal change since fine changes in contrast are imperfectly recorded. PMID- 8350730 TI - Use of a projection reconstruction method to decrease motion sensitivity in diffusion-weighted MRI. AB - Diffusion-weighted MRI is a clinically useful technique, but its utility is compromised by high sensitivity to patient motion. Use of radial-scan data acquisition and projection reconstruction, rather than the conventional Fourier imaging method, can substantially reduce the sensitivity to global translational motion of the object. The basis of this concept and a demonstration of the technique in an animal imaging experiment are presented. PMID- 8350731 TI - In vivo degradation of silicones. AB - 29Si nuclear magnetic resonance (NMR) spectroscopy is applied to study the degradation of polysiloxanes (silicones) in vivo. Our results with animal models show that silicone migrates from the implant to the liver (29Si resonance at -20 ppm) and new silicon containing compounds form after the silicones are introduced into the rats. The new 29Si resonances in the chemical shift range of -40 to -85 ppm are related to hydrolyzed silicone, those at -90 to -115 ppm are indicative of the presence of silica (SiO2), and the peaks observed at -120 to -150 are related to high coordinated silicon complexes. These resonances are not present in the 29Si spectra of the silicones before implantation. Our findings demonstrate that silicones are not metabolically inert. PMID- 8350732 TI - Incorporating prior biases in network models of conceptual rule learning. AB - A series of simulations is reported in which extant formal categorization models are applied to human rule-learning data (Salatas & Bourne, 1974). These data show that there are clear differences in the ease with which humans learn rules, with the conjunctive the easiest and the biconditional the hardest. The original ALCOVE model (an exemplar-based model), a configural-cue model, and two-layer backpropagation models did not fit the rule-learning data. ALCOVE successfully fit the data, however, when prior biases observed in human rule learning were implemented into weights of the network. Thus, current empirical learning models may not fare well in situations in which learners enter the concept-formation situation with preconceived biases regarding the kinds of concepts that are possible, but such biases might nevertheless be captured within these models. By incorporating preexperimental biases, ALCOVE may hold promise as a comprehensive category-learning model. PMID- 8350733 TI - Declarative and nondeclarative memory in opposition: when prior events influence amnesic patients more than normal subjects. AB - Amnesic patients and normal subjects read the names of nonfamous persons. Then, after being told that all the names were nonfamous, subjects judged the fame of names on a mixed list of new famous names, old nonfamous names, and new nonfamous names. Finally, they took a recognition memory test involving old and new nonfamous names. In this way, declarative (explicit) memory and nondeclarative (implicit) memory were placed in opposition. That is, recollection that a name had been recently presented (and was therefore nonfamous) opposed the facilitatory effect by which prior presentation ordinarily increases the tendency to judge that name as famous. Normal subjects exhibited good recognition memory and no fame-judgment effect--that is, no difference in fame judgments for new and old nonfamous names. By contrast, for the amnesic patients recognition memory was poor, but a strong fame-judgment effect occurred--that is, amnesic patients judged old nonfamous names as famous. The results provide additional evidence that the fame-judgment effect is supported fully by nondeclarative (implicit) memory and is independent of the limbic/diencephalic brain structures damaged in amnesia. PMID- 8350734 TI - Evidence for implicit scaling in comparative judgment. AB - In two experiments, we examined the effects of manipulating the density of stimuli on comparison difficulty in a comparative judgment task. In Experiment 1, subjects was slower at judging the relative size of a pair when the members were adjacent items in the linear order than when the members were separated by items of intervening magnitudes. In Experiment 2, the advantage of choosing the larger rather than the smaller of two large stimuli (e.g., the congruity effect) increased when the linear order included many small items. In contrast, the advantage of choosing the smaller of two small items increased when the linear order included many large items. The applicability of the range-frequency theory (Parducci, 1965) to these results is discussed. PMID- 8350735 TI - The separability of space and time: dimensional interaction in the memory trace. AB - The speeded-classification paradigm, adapted from the study of perceptual interactions, was used to examine interactions among features of the short-term memory trace. In each of four experiments, a trial began with the presentation of a pair of stimuli, each member of which occurred either first or second in time and above or below a fixation point. One of the two stimuli was then presented again, and the task was to classify its prior temporal (Experiments 1 and 3) or spatial (Experiments 2 and 4) position. The main question of interest asked whether subjects could selectively attend to one of these occurrence dimensions while ignoring irrelevant variation along the other. The results suggested that whereas subjects can selectively ignore temporal or spatial variation when no recall of the irrelevant dimensions value is required, they suffer interference when values on both dimensions must be remembered. The obtained patterns of interference are consistent with postperceptual interactions of the spatial and temporal components of the memory trace. PMID- 8350737 TI - How apparent motion affects mental rotation: push or pull? AB - Subjects were timed as they judged whether a small bar perpendicular to one side of a clockhand would point left or right if the hand was pointing upward (i.e., at the 12:00 position). The clockhand was shown in two successive orientations 30 degrees apart, so that it was perceived to jump from one to the other, but the bar was included at only one of the two orientations. Analysis of reaction times as a function of angular orientation showed that the subjects "mentally rotated" the clockhand to the upright position before making their decisions. When the bar appeared on the second presentation, the jump had no significant influence on mental rotation but when it appeared on the first presentation, the estimated orientation from which the clockhand was mentally rotated was "dragged" in the direction of the jump. PMID- 8350736 TI - Memory for position and dynamic representations. AB - Memory for the position of an object is biased. When asked to judge whether an object has changed its position with respect to a position shown a few milliseconds before, observers tend to detect the displacement more often when the displacement is not in the expected direction (downward for a falling object). The hypothesis proposed by Freyd (1983, 1987) states that the internal representation of an object is intrinsically dynamic. Therefore, the forces perceived as acting on the object affect the representation. Quantitative predictions of this model were tested in three experiments by measuring memory distortion for the position of an object on an inclined plane. Angle of inclination and retention interval were varied. The results for different inclinations support the physical model. The time course of the memory distortion suggests a new view about the relation between this phenomenon and very short term memory. PMID- 8350738 TI - Rate of imagery processing in two versus three dimensions. AB - A series of five experiments was conducted to test the optimal speed for performing two- and three-dimensional imagery tasks. Subjects were required to keep track of the location of a pathway in an imagined matrix, as the directions of its successive movements were described verbally. Matrices varied in size and in number of spatial dimensions, with two-dimensional matrices drawn on cardboard and three-dimensional ones built from wooden blocks. When subjects were able to dictate the rate of presentation of the terms describing the pathway, they preferred slower rates for three-dimensional than for two-dimensional stimuli. In subsequent experiments, very fast presentation rates had a larger detrimental effect on performance with three-dimensional matrices than with two-dimensional matrices. A comparison of the patterns of performance for subjects who generally scored high with the patterns for those who scored low showed a stronger effect of dimensionality for poor performers, suggesting that individual differences mediate performance on the task. PMID- 8350739 TI - A case study of anomaly detection: shallow semantic processing and cohesion establishment. AB - Although the establishment of a coherent mental representation depends on semantic analysis, such analysis is not necessarily complete. This is illustrated by failures to notice the anomaly in questions such as, "When an airplane crashes, where should the survivors be buried?" Four experiments were carried out to extend knowledge of what determines the incidental detection of the critical item. Detection is a function of the goodness of global fit of the item (Experiments 1 and 2) and the extent to which the scenario predicts the item (Experiment 3). Global good fit appears to result in shallow processing of details. In Experiment 4, it is shown that if satisfactory coherence can be established without detailed semantic analysis, through the recruitment of suitable information from a sentence, then processing is indeed shallow. The studies also show that a text is not understood by first producing a local semantic representation and then incorporating this into a global model, and that semantic processing is not strictly incremental. PMID- 8350740 TI - A translation-based generation effect in bilingual recall and recognition. AB - Two experiments were performed with incidental study procedures in which generation effects were observed for relatively balanced French-English bilingual subjects on measures of both free recall and recognition. Experiment 1 used a within-subject design, and Experiment 2 used a between-subject design. In both experiments, reading translations and reading same-language repetitions generally resulted in similar amounts of retention. Experiment 2 and Experiment 3 also showed that the generation effect was abolished under intentional study procedures because of an enhancement of reading-based retention. The results suggested that previous failures to obtain a translation-based generation effect may have been due to the use of intentional study procedures. The pattern of effects was explained in terms of a single-code model of bilingual linguistic representation and an individual-item processing interpretation of the generation effect. PMID- 8350742 TI - "That man's father is my father's son": the roles of structure, strategy, and working memory in solving convoluted verbal problems. AB - Normative data (N = 896) collected on solutions to the traditional reasoning problem "Brothers and sisters have I none,/That man's father is my father's son" was the platform for a set of experiments to investigate the roles of problem structure, subject strategy, and working memory in error making in a class of verbal problems. The normative data revealed that the modal, but incorrect response to the brothers and sisters problem was "himself," whereas the correct response of "son" was given by only 17% of subjects for the traditional version above, rising to 40% for a reordered novel version. This problem's structure, identified as a double-modifier structure, was found to produce similar response patterns across a range of verbal problems. Results from (1) syntactical structure manipulations (e.g., "My father's son is the father of that man"), and (2) efforts to teach subjects to use a linear strategy (a sequence of steps), interpreted within a framework of Just and Carpenter's (1992) capacity theory of comprehension, suggested that working memory overload varies across within structure modifications and subjects. Furthermore, this overload may be compounded by subjects' choices of strategy. PMID- 8350741 TI - Checklist procedures and the cost of automaticity. AB - Automaticity is usually discussed in terms of its benefits. Automaticity has, however, a cost that manifests itself in procedures that are highly routinized but require close attention, such as verbal checklist procedures. In such procedures, errors occur because the routine leads to automaticity. In three paper-and-pen experiments, we tested this manifestation and investigated ways to decrease automaticity in verbal checklist procedures. In the experiments, subjects proofread sets of multiplication problems to detect erroneous operations, simulating the checklist procedure. In Experiments 1 and 2, two conditions were compared: a fixed-order condition (in which each set contained operations in the same order) and a varied-order condition (in which the operations were in a different order in each set). In Experiment 1, proofreading times were measured to establish the role of fixed sequential order as a consistent environment promoting the emergence of automaticity. In Experiment 2, we introduced errors into the material, and in Experiment 3 we introduced "alerting" conditions to interfere with the development of automaticity. The results indicated that the subjects in the varied-order and alert conditions detected significantly more errors than did those in the fixed-order condition. The implications of the findings for current theories of automaticity are discussed as well as those for the design of checklist procedures. PMID- 8350744 TI - Influence of manipulated category knowledge on prototype classification and recognition. AB - The recognition and classification of category members was explored, following a variable number of learning trials. In Experiment 1, subjects received 1 or 9 learning trials, followed by a recognition-then-classification test containing old, new, prototype, and foil patterns. In Experiment 2, subjects received 1, 6, or 12 trials, and made either classification or recognition judgments. In each experiment, classification accuracy for all item types was at near-chance performance after a single trial but steadily increased with increased learning trials. On the transfer test, oldness judgments were highest for the category prototype after a single trial. However, with increased learning trials, oldness judgments increased for old instances and decreased for the category prototype and new instances. We suggest that false recognition of the category prototype, especially after a single learning trial, need not reflect an abstraction process. We discuss the possibility that an abstracted prototype may emerge with additional learning as an unfamiliar, ideal point. PMID- 8350743 TI - Why do pictures produce priming on the word-fragment completion test? A study of encoding and retrieval factors. AB - Three experiments examined why pictures produce priming on the word-fragment completion test, despite the fact that there is no match between the physical features of the picture and the word fragment. Pictures and words were presented as primers, and performance on the word-fragment completion test was measured; encoding and retrieval conditions were varied. Experiments 1 and 2 examined the role of picture labeling by increasing the presentation rate and by introducing a shadowing task during encoding; labeling appears to play a role in priming. In Experiment 3, the word fragments were presented for 500 msec, and subjects were required to provide a solution immediately. Word priming was unaffected, but picture priming was eliminated, suggesting that word fragments enable efficient recovery of perceptually similar primes (i.e., words), but slower and less direct recovery of conceptually similar but physically dissimilar primes (i.e., pictures). PMID- 8350745 TI - Effects of phonological similarity and concurrent irrelevant articulation on short-term-memory recall of repeated and novel word lists. AB - The extent to which phonological similarity of list words impairs short-term memory recall was investigated in two experiments. Experiment 1 showed that the phonological-similarity effect occurred both when list words were repeatedly sampled from a small set and when they were new on every trial, both when word order information was required and when it was not. Furthermore, the adverse effect of phonological similarity on recall was apparent on the initial lists recalled, did not change over trials, and cannot be attributed to increasing levels of proactive inhibition across lists. In Experiment 2, subjects were required to count repeatedly to six during list presentation. Concurrent irrelevant articulation lowered recall and abolished the phonological-similarity effect for both repeated and novel word lists. PMID- 8350747 TI - Membrane fusion techniques. Part A. PMID- 8350746 TI - Choosing versus rejecting: why some options are both better and worse than others. AB - A previously unobserved pattern of choice behavior is predicted and corroborated. In line with the principle of compatibility, according to which the weighting of inputs is enhanced by their compatibility with output, the positive and negative dimensions of options (their pros and cons) are expected to loom larger when one is choosing and when one is rejecting, respectively. Subjects are presented with pairs of options, one of which--the enriched option--has more positive as well as more negative dimensions than does the other, impoverished, option. Because positive dimensions are weighted more heavily in choosing than in rejecting, and negative dimensions are weighted more heavily in rejecting than in choosing, the enriched option tends to be chosen and rejected relatively more often than the impoverished option. These findings are extended to nonbinary decision problems, and their implications for the rational theory of choice and for everyday decisions are discussed. PMID- 8350748 TI - Fusion of semispherical membranes. PMID- 8350749 TI - Measurement of interbilayer adhesion energies. PMID- 8350750 TI - Forces between phospholipid bilayers and relationship to membrane fusion. PMID- 8350751 TI - Lipid mixing assays to determine fusion in liposome systems. PMID- 8350753 TI - Electrofusion. PMID- 8350754 TI - Membrane electrofusion: a paradigm for study of membrane fusion mechanisms. PMID- 8350752 TI - Chemically induced fusion of erythrocyte membranes. PMID- 8350756 TI - Polyethylene glycol and electric field-mediated cell fusion for formation of hybridomas. PMID- 8350755 TI - Electrofusion of cells: hybridoma production by electrofusion and polyethylene glycol. PMID- 8350757 TI - Selective B lymphocyte--myeloma cell fusion. PMID- 8350758 TI - Biochemical and morphological assays of virus entry. PMID- 8350759 TI - Fusion assays monitoring intermixing of aqueous contents. PMID- 8350760 TI - Preparation, properties, and applications of reconstituted influenza virus envelopes (virosomes). PMID- 8350761 TI - Intermembrane lipid-mixing assays using acyl chain-labeled coumarinyl phospholipids. PMID- 8350762 TI - Electron microscopy of virus--liposome fusion. PMID- 8350764 TI - Phosphorus-31 nuclear magnetic resonance in membrane fusion studies. PMID- 8350763 TI - Fluorescence lifetime measurements to monitor membrane lipid mixing. PMID- 8350765 TI - Fusion of spherical membranes. PMID- 8350766 TI - Surface chemical techniques in membrane fusion. PMID- 8350767 TI - Extrathymic pathways of T-cell differentiation: a primitive and fundamental immune system. AB - In addition to an intrathymic pathway of T-cell differentiation, extrathymic pathways of T-cell differentiation have recently been demonstrated to occur in multiple sites in mice. Such sites include the sinusoids of the liver, the intraepithelial region of the intestine, and the omentum of the peritoneal cavity. Although these extrathymic pathways are minimal at a young age, they become predominant with aging. Extrathymically differentiated T cells display many properties distinct from those of regular T cells of thymic origin. For instance, they consist of a considerably large proportion of gamma delta T cells as well as alpha beta T cells, contain double-negative CD4-CD8- cells and self reactive oligoclones, constitutively express the II-2 receptor beta-chain, and have an alpha alpha homodimer of CD8 if they carry it. Cumulative evidence reveals that the extrathymic pathways comprise a primitive and fundamental immune system in the body and play a pivotal role in immune reactions under conditions of aging, bacterial infections, malignancies, autoimmune diseases, and pregnancy. PMID- 8350769 TI - Cytotoxic effect of hemolytic culture supernatant from Enterococcus faecalis on mouse polymorphonuclear neutrophils and macrophages. AB - We reconfirmed that the LD50s of hemolytic Enterococcus faecalis strains were significantly less than those of nonhemolytic E. faecalis strains in normal mice. Hemolysin produced by E. faecalis lysed human, horse, rabbit, and mouse erythrocytes, but not cow and sheep erythrocytes. Sphingomyelin comprises a part of the lipid composition of the erythrocyte membrane of all mammalian species tested. But phosphatidylcholine exists only in human, horse, rabbit, and mouse. These two lipids inhibited lysis of horse erythrocytes by hemolytic E. faecalis. Phosphatidylcholine is probably the binding component on the membrane of erythrocytes for E. faecalis hemolysin. The hemolytic culture supernatant lysed not only erythrocytes but also mouse polymorphonuclear neutrophils (PMNs) and macrophages. PMID- 8350768 TI - Comparison of the virulence for mice of Mycobacterium avium and Mycobacterium intracellulare identified by DNA probe test. AB - The virulence of various serovars of Mycobacterium avium and M. intracellulare identified by DNA probe test was compared with each other. We found species- and serovar-dependencies of M. avium complex (MAC) virulence to mice in terms of mortality, incidence of lung lesions and bacterial load in the visceral organs, as follows. First, human- or environment-derived M. intracellulare was more virulent for mice, as compared to M. avium isolated from patients or environmental sources. Second, the virulence of MAC isolates belonging to serovars 1, 8, 9 (M. avium), 14 and 16 (M. intracellulare) is in the order of serovars 16 > 14 > 8 > 1 > 9. These aspects were different from those for MAC virulence to human and bird, swine and cattle. PMID- 8350770 TI - Development and evaluation of capture enzyme-linked immunosorbent assays for detection of immunoglobulin G and M antibodies to group A streptococcal antigens. AB - Capture enzyme-linked immunosorbent assays (ELISAs) were developed to detect immunoglobulin G and M antibodies to group A streptococcal (GAS) antigens, streptolysin O, streptokinase, and group A carbohydrate. The sensitivities and the specificities of the IgM capture ELISAs to each GAS antigen were high enough to distinguish the patients with GAS infections (diagnosed as GAS pharyngitis or scarlet fever) from the control groups (healthy people and patients with pharyngitis from whom GAS could not be isolated). On the other hand, the specificities of the IgG capture ELISAs were not very effective in diagnosis of GAS infections. When the capture ELISA and an indirect ELISA detecting IgM antibodies to group A carbohydrate were compared, false-positive reactions due to rheumatoid factor occurred in the indirect ELISA, but did not occur in the capture ELISA. These results indicate that the capture ELISA works better than the indirect ELISA in detecting the IgM antibody, and that the IgM capture ELISA to GAS antigen provides a rapid and highly reliable serodiagnosis for GAS infections employing only a single serum. PMID- 8350771 TI - Isolation of scrapie agent from the placenta of sheep with natural scrapie in Japan. AB - A five-month-pregnant Suffolk sheep histologically diagnosed as spontaneous scrapie was studied. Western blot analysis was performed with rabbit serum against the sheep scrapie-associated fibrils (SAF). In the proteinase K (pk) treated parental brain and spleen samples, three major bands (15 K, 18 K, and 23 K) were detected. These major bands were not detected from the placenta. Infectious agents were isolated in mice from the brain samples but not from the placental homogenates. In another case of a three-month-pregnant Corriedale sheep without any clinical sign of, but histologically diagnosed as scrapie, was also studied in a similar approach. In the parental brain samples, three major bands (15 K, 18 K and 23 K) were detected. SAF protein was not detected in the parental spleen and placenta. No bands reactive with the antiserum were detected in any other samples from the fetal brain and spleen in both cases. However, infectious agents were isolated in mice from both brain and placental homogenates. Since the placenta is an important site of natural infection, it is worthwhile to study these tissues for the epidemiological study of scrapie infection. PMID- 8350773 TI - Neurologic abnormalities in two dogs suspected Lyme disease. AB - A 2-year-old mongrel dog developed neurological signs following tick bite. These included astasia, persistent tonic convulsions and hyper-reflexia. Both serum IgG and IgM antibody titers against Borrelia burgdorferi were positive in enzyme linked immunosorbent assay (ELISA). The neurological signs subsided after high dose penicillin and streptomycin treatment. A strain of spirochetes (P427a) was isolated from the midgut of Ixodes persulcatus feeding on the dog. Morphological characteristic, immunological property and protein profile revealed that the isolate was B. burgdorferi. Similarly, a 2-year-old Labrador retriever dog developed neurological signs after tick bite and showed a positive IgG antibody titer against B. burgdorferi. Antibiotic treatment was effective also in this case. These findings suggest that neurological symptoms shown in both dogs were caused by infection with B. burgdorferi. PMID- 8350772 TI - Cholera toxin inhibits lethal hit stage of natural killer cell-mediated cytotoxicity. AB - Cytolytic process which was affected by cholera toxin (CT) resulting in the loss of natural killer (NK) cell activity was analyzed. Conjugate formation assay, membrane phospholipid methylation assay and serine esterase (granzyme A) release assay were used to determine the stage of the CT-induced inhibition of NK cell mediated cytotoxicity. A human NK cell line YT cell-mediated cytotoxicity was completely abolished by CT pretreatment or addition of CT to the assay system. The conjugate formation assay revealed that the binding between YT cells and target cells was not affected by CT. The defined triggering stage which is coupled with membrane phospholipid methylation was not affected by CT treatment, either. On the other hand, the lethal hit stage which is represented by serine esterase (SE) release was completely inhibited by CT treatment of YT cells. Therefore, CT inhibits the stage after binding and triggering--i.e., lethal hit stage of NK cell-mediated cytotoxicity. The results also suggest that there exists a CT-sensitive negative cytotoxic signal transduction pathway as well as usual positive signal transduction pathway and these pathways might cross talk each other in the NK cell cytotoxic process. PMID- 8350774 TI - Diabetes and its complications may be caused by inadequate circulation. A new concept. AB - Students of diabetes have noted that the so-called vascular complications of the disease appear with little or no consistency. Uncontrolled patients may have no vascular problems. Contrarywise obsessive compulsive individuals who follow every dietary regimen perfectly and take their prescriptions faithfully may have horrendous vascular difficulties. These experiences brought me to the conclusion that the 'complications' were really a component of the disease rather than the result of it. In an effort to find a unified concept of the disease it seemed reasonable to conclude that inadequate circulation to the islets may be a cause of the chemical constellation that we call diabetes. Vascular pathology may appear haphazardly in various arteries. Thus some will develop cerebrovascular disease, others coronary manifestations while still other patients will experience peripheral vascular symptoms. Is it not possible that defective circulation to the pancreas might be an aetiological factor in the development of diabetes? These observations lend credence to the concept that arterial pathology may actually precede the appearance of clinical diabetes. PMID- 8350775 TI - The glutathione cycle is the creative reaction of life and cancer. Cancer causes oncogenes and not vice versa. AB - Life is definable as a chemical reaction which obeys exponential growth and dies if reversed. Such a reaction must be the commencement of all life so that every evolved form of it inherits these characteristics. As no single reaction known has these two features, life must be a combination of two or more reactions which whilst obeying all the classical laws of physics and chemistry assume an exponential form and effectively act as being irreversible. The reactions of glutathione--oxidation and reduction--when combined in sequence as a cyclical process fulfill these criteria. The cyclic changes of glutathione from reduced to oxidised to reduced forms must therefore be the reaction which creates life and is responsible for cancer's growth. 434 mHz electromagnetic radiation stimulates cancer growth rate by forcing this cycle into activity. Proof of this hypothesis is the long-term control of cancer in 11 patients treated with oxidised glutathione and 434 mHz radiation. Genetic material does not contain any energy system with exponential form, neither is it self-replicating. Genetic material will only reproduce if placed within an immortal cell in which all controls of the glutathione system have been lost, as in a cancer cell. Oncogenes must be the product of cancer and not the reverse. PMID- 8350776 TI - DNA triboluminescence and carcinogenesis. PMID- 8350777 TI - Stimulation causing the double effect as in dyspraxia, a universal mechanism of disease, and auto-electrocution, the fatal factor. AB - Almost every action in the body involves the nervous system which uses electricity for its speed and versatility. Operating and controlling muscular activity is a major function of the nervous system. Muscles are paired so every normal contraction requires a reciprocal relaxation of its doppelganger (Newton said 'Equal and opposite'). Minor failures of co-operation, i.e. neuromuscular dysfunction make common survivable diseases. Multiple and major stimuli can create chaotic conflicts within these couplings and lead to fatalities. Excessive, abnormal, even ordinary stimulation will cause the (irritable?) partner(s) which should relax also to contract. Thus function is impaired or impossible. In the limbs faulty neuromuscular co-ordination is obvious as stiffness, Parkinson's Disease, Erb's Palsy etc. Less evident, it is even more important in the cardiovascular, gastrointestinal, genitourinary and respiratory systems. PMID- 8350778 TI - Could development of malignant mesothelioma be induced by Yersinia enterocolitica infection? AB - Two out of 458 hospitalized patients with Yersinia enterocolitica infection developed malignant mesothelioma of pleura viz. pericard; both died after a few months. Malignant mesothelioma of the pleura is commonly related to asbestos exposure, whereas pericardiac mesothelioma is an extremely uncommon neoplasm. The possible promotion of malignant mesothelioma by the Yersinia enterocolitica infection should not be disregarded, as the infection may launch chronic immunological reactions resembling those observed among asbestos workers. PMID- 8350779 TI - Dorsal root ganglia may be reservoirs of viral infection in multiple sclerosis. AB - There are presently two competitive theories that attempt to explain the etiology of multiple sclerosis (MS). Briefly summarized, they are: 1. An infection, probably of viral type, may attack the oligodendroglia of the central nervous system; or, 2. An autoimmune process may begin with an infection of the peripheral lymphatic immune system, producing antibodies that cross the blood brain barrier, leading to myelinoclasia. Since 1935, research has been directed toward myelin of the central nervous system and the myelin sheaths of peripheral nerve; however, dorsal root and cranial sensory ganglia (DRG) have apparently not been studied. The present hypothesis states that an infectious agent (probably viral) finds privileged sanctuary in the dorsal root and cranial sensory ganglia (DRG): thereafter periodically invading the spinal cord, brain, or peripheral nerve. Previously reported erratic spinal fluid viral titers and cultures can be explained by differences in the anatomy of the DRG in which there is a variable and limited contact of spinal fluid with sensory ganglia. Clues to this hypothesis were noted by the author during routine neurological examinations of patients with MS, in which sensory signs and symptoms were frequently encountered. This clinical observation has also been reported by others who found such symptoms in 75% of MS patients, ranking second only to incoordination. PMID- 8350780 TI - Abnormal fluctuations of acetylcholine and serotonin. AB - Abnormal fluctuations of acetylcholine and serotonin might cause, or be correlated with, a variety of symptoms. This communication cites evidence which suggests that fluctuations of serotonin might have a causative role in migraine, mania, and depression and that fluctuations of acetylcholine might have a causative role in epilepsy, catalepsy, and Kleine-Levin attacks. PMID- 8350781 TI - Louis Bolk revisited: I. Is the human lung a retarded organ? AB - The human lung shows permanent retention of certain features (such as the absence of an infracardiac lobe, or the subdivision of the lobes in lobules) found in most mammal fetuses or youngsters. This phenomenon seems to be in line with the fetalization theory of Louis Bolk, who considered man as a retarded and unspecialized mammal. Moreover, the retention of certain fetal or unspecialized traits in the human lung favors a body configuration suited to an upright stance. This suggests that the generalized mammalian body plan is that of a bipedal being. PMID- 8350782 TI - Future impact of molecular biology and biotechnology on bacterial and viral diseases. AB - The advent of recombinant DNA technology has already made a significant impact on various aspects related to the basic understanding of pathogenic mechanisms in infectious diseases, as well as practical applications related to diagnostics and prevention. The present paper discusses recent technological innovations and increased analytical capabilities which promise to have an even more significant impact on the control of viral and bacterial diseases. PMID- 8350784 TI - A study of primary drug resistance in pulmonary tuberculosis in west Malaysia 1984-1987. AB - Eight hundred and fifty-six strains of Mycobacterium tuberculosis from previously untreated patients with pulmonary tuberculosis from various states in West Malaysia were studied during the period 1984 to 1987. All the strains were tested for in vitro susceptibility to the anti-tuberculosis drugs isoniazid (INH), streptomycin (SM), rifampicin (RMP) and ethambutol (ETB). One hundred and twenty one of the isolates (14.18%) were resistant to 1 drug while 17 (1.97%) were resistant to 2 drugs. No strain was found to be resistant to more than 2 drugs. The prevalence of primary resistance to INH was 4.20%, SM was 7.59%, RMP was 0.95% and ETB was 1.44%. In 1.86% of isolates, resistance was noted to both INH and SM, while 0.11% were resistant to both RMP and ETB. There was no significant difference in distribution of resistant bacilli between the sexes (p > 0.01). PMID- 8350783 TI - Cholesterol reduction therapy: a double-edged knife. AB - Cholesterol reduction reduces ischaemic cardiovascular morbidity and mortality in the asymptomatic healthy population as well as in those with known coronary artery disease. Angiographic studies have also demonstrated regression of atherosclerotic plaques as well as retardation of new atheroma formation with such therapy. Yet, there is a consistent inability to reduce overall mortality in cholesterol-lowering drug trials. An excess of suicide, homicide and violence has been attributed to cholesterol reduction interfering with membrane lipids and receptors, leading to aggressive behaviour. The risk and benefits of cholesterol reduction must thus be weighed in the individual patient; it is more useful in those with known coronary artery disease who are at high risk of subsequent ischaemic cardiovascular events. PMID- 8350785 TI - Risk behaviour associated with HIV infection among drug abusers seen at the general Hospital, Kota Bharu, Kelantan. AB - Sixty-one serologically positive HIV infected drug abusers admitted to the Drug Ward, General Hospital, Kota Bharu, were interviewed for possible risk behaviour and AIDS awareness. Fifty-eight subjects were IV abusers while the other 3 were non-IV abusers. All the IV abusers had shared injecting equipment with no regard for sterility. There was non-usage of condoms among those sexually active. Though AIDS awareness was high, there was a lack of risk behaviour change. The drug abusers appear to be a problem group in HIV control measures. Educating the drug abusers and commitment by them to alter risk behaviour is needed. PMID- 8350786 TI - Prevalence of sexually transmitted diseases among female drug abusers in Malaysia. AB - The prevalence of sexually transmitted diseases (STD) among female drug abusers was determined by screening 130 new inmates of a rehabilitation centre. The majority of the subjects (77.7%) were self-confessed sex workers. A high prevalence of syphilis (50.8%), hepatitis B (52.2%), moniliasis (23.8%) and trichomoniasis (19.2%) were noted. Gonorrhoea vaginitis was seen in 8.5%, which was low compared to previous studies. Six subjects were seropositive for human immunodeficiency virus (HIV), with 5 of them admitting to needle sharing and working as prostitutes. More than half of them harboured 2 or more STD. A rich reservoir of STD was seen among the drug abusers. With more evidence now available concerning the ease of HIV transmission associated with ulcerative STD, a stage could be set for greater heterosexual HIV transmission. As part of the rehabilitation process, female drug abusers need a thorough screening for STD followed by aggressive treatment regimens. PMID- 8350787 TI - Pattern of alcoholism in the General Hospital, Kuala Lumpur. AB - This study establishes the prevalence rate for alcoholism among the inpatients of the General Hospital, Kuala Lumpur, as 11%, but as 25% among the drinking population. It also describes the demographic profile of the alcoholic as compared to the non-alcoholic drinker and the non-drinker and suggests that certain vulnerability factors could contribute to the development of alcoholism. A trend noted is also the changing racial trends in the use of alcohol. PMID- 8350789 TI - Phenomenological differences of hallucinations between schizophrenic patients in Penang & Kelantan. AB - Two hundred and seventy patients with schizophrenia (104 patients in Kelantan and 166 patients in Penang) were interviewed using the Present State Examination to elicit the differences in the phenomenology of their hallucinations. The results indicate that there are significant differences in the phenomenology of hallucinations between the Malays of Penang and Kelantan and also among some Chinese patients. These findings indicate that culture does affect the phenomenology of schizophrenia, even among people of the same race but of different regions. PMID- 8350788 TI - Characteristics of psychiatric admissions and aspects of overcrowding at the general Hospital, Kuala Lumpur. AB - This study examined admissions, final diagnoses and mean duration of stay of patients in the Psychiatric Wards at the General Hospital, Kuala Lumpur. The male ward was severely overcrowded by 125% over the maximum bed capacity. The majority were psychotic, mainly schizophrenic. The female ward had 76% occupancy, also mainly psychotic. Neurotics, alcohol dependents and personality disorders formed less than 5% of the admissions. There was no difference in the mean duration of stay of patients of both UKM and GHKL Units stratified for diagnosis and disposal except for newly diagnosed schizophrenics. There is an urgent need for more male psychiatric beds/wards. PMID- 8350790 TI - The EEG and epilepsy in Kelantan--a hospital/laboratory-based study. AB - Five hundred and ninety three cases of clinically diagnosed and suspected epilepsy were analysed as regards to the EEG (standard scalp electrode recording) features for confirmation and typing. Fifty-five per cent of all clinically diagnosed adult epileptics were confirmed by the EEG with the initial record, and the EEG confirmatory rate in children was higher at 92%. The frequency of generalised epilepsy as confirmed by the EEG was found to be 86% in adults and 92% in children, reflecting a higher proportion of generalised epilepsy in the population than reported elsewhere. Clinical diagnosis of partial epilepsy was often subsequently shown to be of generalised type on EEG. PMID- 8350792 TI - Lung function in Malay children. AB - We conducted a study to measure the peak expiratory flow rate (PEFR), forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in a group of normal Malay primary school children aged 7 to 12 years. PEFR was measured in 920 children (482 boys and 438 girls) while FVC and FEV1 were measured in 292 of them (168 boys and 124 girls). In agreement with previous studies, we found that PEFR was correlated with age and height of the subjects but FVC and FEV1 were correlated with height only. Prediction equations for all 3 lung function indices for Malay boys and girls were formulated. In comparison with the lung function values from Western and Chinese subjects, the lung function values in our subjects are lower. PMID- 8350791 TI - Computed tomography (CT) of orbital pseudotumour. AB - Orbital pseudotumour is a non-specific inflammatory disease. Its highly variable clinical and radiographic presentation makes specific diagnosis difficult. This study on 31 proven cases of pseudotumour shows that unilateral involvement, retroorbital fat infiltration and enlargement of multiple extraocular muscles with involvement of the tendinous insertions are key computed tomography CT features which help to establish the diagnosis of orbital pseudotumour. PMID- 8350793 TI - Spirometric studies in Malaysians between 13 and 69 years of age. AB - Spirometry was performed on 1,999 subjects (1,385 males and 614 females) ranging in age from 13 to 69 years and comprising of all the main races in Malaysia. They were divided into 6 age groups. Mean forced vital capacity (FVC) in the males and females was 3.49 +/- 0.02 L and 2.51 +/- 0.02 L respectively. Both FVC and FEV1 correlated negatively with age. Regression analysis on data between the ages of 20 to 69 years revealed an age-related decline in FVC of about 30 ml per year of life in the males and 22 ml per year in the females. Multiple stepwise regression of the data for the prediction of an individual's FVC above the age of 20 years gave an equation for the males: FVC = 0.0407 (height)-0.0296 (age)-2.343 L and for the females: FVC = 0.031 (height)-0.022 (age)-1.64 L. Predicted FVC values derived from equations based on other populations were considerably higher than the observed mean in this study, re-emphasizing the need to be cautious when applying formulae derived from one population to another. Grossly erroneous conclusions may be reached unless predicted equations for lung-function tests for a given population group are derived from studies based upon the same population group. PMID- 8350794 TI - A registry of patients with end stage renal disease--the experience at hospital Sultanah Aminah, Johor Baru. AB - A registry of patients with end stage renal disease was started from 1st January 1990 at Hospital Sultanah Aminah, Johor Baru. There were 126 patients in 1990 and 129 in 1991. The peak age was 31 to 60 years old; males outnumbered females 1.5:1. Forty-three to fifty-six percent presented with small kidneys. Seventeen to twenty percent of patients had diabetes mellitus. In 1991, the racial distribution of patients was Malay: 50.4%, Chinese: 39.5%, Indian: 7.8% and others: 2.3%. The incidence of end stage renal disease in Johor Baru district was 79 per million per year in 1990 and 86 per million in 1991. PMID- 8350795 TI - Occurrence of human rabies in peninsular Malaysia. AB - The occurrence of a case of human rabies in Peninsular Malaysia is reported. Despite the various control measures taken, sporadic cases of rabies have continued to occur in Peninsular Malaysia, especially in the northern states. Clinical awareness of the occurrence of rabies is therefore important and effective post-exposure prophylaxis should be instituted as soon as possible to prevent the possible occurrence of this dreaded disease. PMID- 8350796 TI - Fibreoptic intubation--a case series and brief review. AB - Fibreoptic intubation has been established as a major advance in the management of difficult or failed intubation in the awake patient. If necessary, it may be performed under general anaesthesia with either spontaneous or controlled ventilation. This should be considered early in the management of failed intubation, before multiple attempts with other techniques lead to haemorrhage and oedema in the airway. We describe here selected case reports to illustrate this in 8 different situations. This is followed by a brief review of the technique and indications of fibreoptic intubation. PMID- 8350797 TI - Epidural buprenorphine and bupivacaine in major gynaecological operations. AB - Eight patients underwent major gynaecological operations. Their post-operative analgesia was provided by epidural buprenorphine 0.15 mg and bupivacaine 0.5%. The efficacy and side-effects of this combination were assessed. All patients had satisfactory analgesia ranging in duration from 10 hours to greater than 36 hours after a single dose injection. No significant side-effect was noted. PMID- 8350798 TI - Changing patterns in the treatment of early breast cancer: a historical perspective and a review of changing local trends. AB - Over the past 50 years, a variety of surgical procedures have been advocated for the treatment of operable breast cancer, ranging from local excision to supraradical mastectomy. Today, the surgical treatment of breast cancer remains highly contentious. We review the historical development of breast cancer surgery and analyse the available evidence supporting conservative procedures. We also express our opinions on the treatment of early breast cancer and illustrate the changing patterns of surgery with our experience at National University Hospital. PMID- 8350799 TI - Antegrade intraoperative colonic lavage. AB - Emergency left-sided colonic resections have traditionally been dealt with by employing staged resections due to the dangers of an anastomosis in unprepared bowel. A small series of 6 patients with left-sided colonic obstruction is presented in which a single stage primary anastomosis was done after an antegrade intraoperative colonic lavage. There were no deaths, infective complications or anastomotic leaks. Major series in the last decade using intraoperative colonic lavage are reviewed as well, to confirm that the method is safe, effective and warrants wider usage locally. PMID- 8350800 TI - Experience with sublabial transseptal transsphenoidal hypophysectomy at the Universiti Kebangsaan Malaysia. AB - The transseptal transsphenoidal hypophysectomy has become a relatively frequent procedure in recent years. We performed 20 such procedures between January 1984 and December 1987 for various pituitary disorders. Significant complications such as CSF rhinorrhea, meningitis, diabetes insipidus, haemorrhage and septal perforation are discussed. The mortality rate for the series was 5%. In analysing the data, we feel that this technique of hypophysectomy is a safe procedure. PMID- 8350801 TI - Fertility following reversal of female sterilization. AB - This retrospective study presents data from 26 women who underwent a reversal of female sterilization. The intrauterine pregnancy rate and ectopic pregnancy rate were 38.5% and 7.7% respectively. The most successful site of tubal anastomosis was isthmic-isthmic anastomosis. The importance of proper patient selection and factors that affect the success rate in attempted reversals are emphasised. The importance of microsurgical approach is highlighted. PMID- 8350802 TI - Actinomycosis of the accessory breast treated with cotrimoxazole. AB - Actinomycosis is a chronic suppurative granulomatous disease caused by the filamentous bacteria, Actinomyces israelii, which was once thought to be a fungus. It is a Gram-positive, aerobic or microaerophillic, non acid-fast hyphal organism which fragments into coccoid or bacillary forms and, unlike the fungus, does not form conidia. Accessory breast tissue usually occurs along the milk lines, frequently in the axilla and rarely in the thighs. Actinomycosis of the breast is very uncommon and we report the case of a multiparous woman who had a painful lump in the axilla which, on histopathologic examination, showed actinomycosis within the accessory breast tissue. PMID- 8350803 TI - Human immunodeficiency virus infection in recipients of living unrelated donor renal transplants--a report of 4 cases. AB - Four cases of Human Immunodeficiency Virus (HIV-1) infection, probably following living unrelated donor renal transplantation done in India, are reported. One of them subsequently developed Acquired Immunodeficiency Syndrome (AIDS). PMID- 8350804 TI - Pain relief with intravenous regional guanethedine in post-traumatic reflex sympathetic dystrophy--a case report. AB - Intravenous regional guanethedine (IVRG), using the Bier's block technique, was given to relieve pain in a 62 year old Indian woman suffering from reflex sympathetic dystrophy. The patient obtained complete pain relief with 2 injections and has remained pain-free for 18 months. PMID- 8350805 TI - Haemophagocytosis in typhoid fever. AB - This report deals with a young man who developed features of haemophogocytosis during the course of typhoid fever. The pertinent clinical and laboratory features of typhoid-associated haemophagocytosis are discussed. The need for blood component replacement therapy in addition to specific anti-microbials to treat haemophagocytosis complicating typhoid fever is stressed. PMID- 8350806 TI - Diagnosis and management of blunt pancreatic trauma: a case report with review of the literature. AB - Details of a young logger who sustained a clean prevertebral transection of the pancreas to the left of the superior mesenteric vessels and a crush injury in segments 2 and 3 of the liver are presented. CT scan was not done but ultrasound scan revealed free intraperitoneal fluid and no comment was made about the pancreas. The pancreatic injury was discovered at laparotomy carried out 24 hours after admission and treated by resection. PMID- 8350807 TI - Septicaemic pulmonary melioidosis with cutaneous pustules. PMID- 8350808 TI - Teronac and teratogenecity. PMID- 8350809 TI - Handwashing at University Hospital. PMID- 8350810 TI - Drug resistant Mycobacterium tuberculosis. PMID- 8350811 TI - Substance abuse and the doctor. PMID- 8350812 TI - Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation. AB - A biologically based model is developed to predict radiation-induced normal tissue complication probability (NTCP) in inhomogeneously irradiated organs such as the lung or the kidney. The organ is assumed to be composed of independent functional subunits (FSUs) organized with a parallel architecture and it is assumed that the complication is produced only if a sufficiently large number of FSUs (the "functional reserve") are destroyed. A general expression for NTCP is derived, as well as simple expressions for the mean and standard deviation of the radiation damage to the FSUs. It is demonstrated that these results for inhomogeneous irradiation reproduce those of the serial and tumor control models when the functional reserve consists of one or all of the FSUs, respectively. When the number of FSUs is large, the dose response for organs with identical characteristics is very steep. Since clinical dose-response curves may arise from populations with varying functional reserves and radiosensitivities, we derive expressions for the NTCP for inhomogeneously irradiated organs that incorporate such variations. PMID- 8350813 TI - Implementation of the ETAR method for 3D inhomogeneity correction using FFT. AB - The equivalent tissue-air-ratio (ETAR) method employs three-dimensional (3D) CT pixel information to approximate scatter dose contribution for inhomogeneity correction. In general, the calculation provides better agreement with measurements than the one-dimensional (1D) methods typically used in commercial treatment planning systems. In its original implementation, the 3D formulation of the ETAR method is modified empirically as a 2D calculation in order to reduce computation time. The modification compromises the use of the method in several treatment geometries. An examination of the ETAR formulation shows that the calculation can be expressed as a convolution and thus can be performed in 3D using fast Fourier transform (FFT) techniques. The algorithm has been implemented as a 3D FFT convolution. Making use of the symmetric properties of the FFT, the new approach shows significant savings in computation time without excessive memory requirement. Despite its fundamental limitations when applied to regions of electronic disequilibrium, the ETAR method offers a practical solution to improving current dose calculation in 3D treatment planning, particularly when the more advanced scatter ray-tracing dose calculation algorithms remain impractical for clinical use. Recent work to extend the method to approximate electron transport is also encouraging. PMID- 8350814 TI - Pressure wave generated by the passage of a heavy charged particle in water. AB - Energy deposition around the trajectories of ionizing particles with linear energy transfer (LET) of 4, 40, and 400 keV/microns in water and subsequent diffusion of deposited heat is calculated using computational fluid dynamics. Immediately after the deposition of energy by the charged particle, the temperature and pressure in the vicinity of the particle track both increase dramatically, leading to the formation of a thermal spike and a pressure wave. Initially, the region of heat deposition is primarily localized to a region called the "thermal core," which has dimensions of 0.3, 1, and 3 nm for particles with LETs of 4, 40, and 400 keV/microns, respectively. Instantaneous peak temperatures within the thermal core were 800 degrees C-2000 degrees C and peak pressures were about 25,000 atm. This sudden deposition of heat in a localized region leads to a very strong shock wave around the particle trajectory, which is shown to last for a duration of 10(-9)-10(-8) s. Even at distances beyond 10 nm away from the particle trajectory, pressures above 100 atm could exist for a duration of up to 10(-11) s. This local and transient environment, created by the passage of a charged particle in a medium, may lead to new mechanisms of radiation action leading to cell damage, as well as to the development of new radiation detectors. PMID- 8350815 TI - Application of fast simulated annealing to optimization of conformal radiation treatments. AB - Applications of simulated annealing to the optimization of radiation treatment plans, in which a set of beam weights are iteratively adjusted so as to minimize a cost function, have been motivated by its potential for finding the global or near-global minimum among multiple minima. However, the method has been found to be slow, requiring several tens of thousands of iterations to optimize 50 to 100 variables. A technique to improve the efficiency for finding a solution is reported, which is generally applicable to the optimization of continuous variables. In previous applications of simulated annealing to treatment planning optimization, only one or two weights are varied each iteration. This approach is to change all weights simultaneously, using random changes that are initially large to coarsely sample the cost function, then are reduced with iteration to probe finer structure. The performance of different methods are compared in optimizing a plan for treatment of the prostate, in which the search space consists of 54 noncoplanar beams and the cost function is based on tumor control and normal tissue complication probabilities. The proposed method yields solutions with similar values of the cost function in only a fraction of the iterations compared either to a fixed single weight adjustment technique, or to a method which combines the Nelder and Mead downhill simplex simulated annealing. PMID- 8350816 TI - "Coordinate transformation as a primary representation of radiotherapy beam geometry" by G. W. Sherouse [Med. Phys. 19(1), 175-179 (1992)]. PMID- 8350817 TI - Low-energy imaging with high-energy bremsstrahlung beams: analysis and scatter reduction. AB - The contrast and zero spatial frequency signal-to-noise ratio produced by a method for radiation therapy portal imaging known as low-energy imaging with high energy bremsstrahlung beams have been mathematically analyzed. The analysis makes extensive use of Monte Carlo techniques and incorporates the detector, the spectrum, phantom, and geometry. The analysis is validated through comparison with measured data including subject contrast measurements and the attenuation of the beam with lead. Scatter reduction is found to be potentially the most effective method to improve contrast and SNR for a film based system. A large fraction of the scatter detected is of a much higher energy than that found in diagnostic radiology. Hence, traditional antiscatter grids, such as those used in diagnostic radiology, are ineffective. The analysis and theory from the literature are applied to design a new grid which is more appropriate for this application. The grid produces a modest improvement according to a contrast detail study. PMID- 8350818 TI - Automatic on-line inspection of patient setup in radiation therapy using digital portal images. AB - A new method is presented for inspection of patient setup in radiation therapy by automatic comparison of the patient position relative to the beam position in portal and simulator images. Quantification of patient-setup errors in terms of translation, rotation, and magnification is achieved by chamfer matching, a robust technique to match drawings and images, which is applied to both anatomy outlines and field edges. Applied to field edges, chamfer matching detects and visualizes deviations in field shape. Applied to anatomy outlines, the matching procedure quantifies and visualizes deviations in patient position relative to the radiation field. To test the method and to judge its feasibility, its behavior for four hundred different patient-setup deviations, which were simulated in four clinical images, was examined. These images show a top view of the pelvic region. The performance was measured in terms of accuracy and success rate for numerous cost functions and distance codings associated with the chamfer matching procedure. An average accuracy of 1.8 mm was found, a success rate of 90%, and an average overall computation time of 3 s on a 486 microcomputer. The whole analysis procedure is fast enough to allow on-line application. PMID- 8350819 TI - Uncertainty analysis of field placement error measurements using digital portal and simulation image correlations. AB - An uncertainty analysis of a field placement error measurement method using correlations between digital portal and simulation images has been performed. This analysis used the Monte Carlo method to simulate random uncertainties arising in image registration and portal field edge detection. The uncertainty analysis used data from a field placement error study to predict the dependences of the measurement method upon image matchpoint number and spatial distribution, image registration, and uncertainties arising in the detection and description of the field edge in a portal image. It was shown that the uncertainty in the field registration had the most significant effect upon the measurement uncertainty, whereas the number of matchpoints had an extremely limited effect (beyond the minimum required for the mathematical procedure used in registration). In contrast, it was shown that an accurate field placement error measurement required that the number of pixels describing a field edge used for comparisons should exceed 20, thus automatically setting a minimum field length necessary for field placement comparisons. It was also shown that the spatial uniformity of the matchpoints in an image pair had a limited effect upon the field placement error measurement, provided that the points are distributed over about 15% of the image area. PMID- 8350820 TI - Verification of radiotherapy treatments: computerized analysis of the size and shape of radiation fields. AB - An automated technique has been developed for the verification of treatment field size and shape in external beam radiation therapy. Portal images from film or digital on-line imaging system are analyzed, and basic parameters are derived to describe the field size and shape from the contour points on the field boundary. The initial set of parameters included length of the perimeter, area, aspect ratio, and orientation angle. The parameters found for the actual field in the portal image are compared against those calculated for the prescribed field and any discrepancies indicated to the operator. The accuracy of the field parameterization scheme has been tested on a number of on-line portal images with varying fields. The relative error did not exceed a few percent in perimeter and area or 2 degrees in the angle, which should be sufficiently low for the detection of major errors in field shaping. PMID- 8350821 TI - Energy distributions from a racetrack microtron measured with a magnetic spectrometer. AB - Energy spectra of accelerated electron beams from a racetrack microtron were measured using a magnetic spectrometer. The spectrometer utilized a 90 degrees dipole magnet. A ray-tracing program was developed to determine the slit positions of the spectrometer based on a detailed map of the magnetic field measured at field strengths corresponding to about 20 and 50 MeV. The total a priori uncertainty (previously often called systematic or class B uncertainty) of the measured most probable energy Ep is 0.22% (one approximate standard deviation) and the a posteriori uncertainty (previously often called random or class A uncertainty) is 0.04% (1 sigma). The estimated energy resolution (delta E/E) of the spectrometer is 4 x 10(-4). Spectral energy distributions of the electron beam were measured at a Ep = 21.1 and 51.6 MeV, and the obtained full width at half-maximum of the energy distributions were 53 and 34 keV, respectively. All the measurements were performed in vacuum to minimize the influence of electron energy loss and scatter. PMID- 8350822 TI - X-ray surface dose measurements using TLD extrapolation. AB - Surface dose measurements in therapeutic x-ray beams are of importance in determining the dose to the skin of patients undergoing radiotherapy. Measurements were performed in the 6-MV beam of a medical linear accelerator with LiF thermoluminescence dosimeters (TLD) using a solid water phantom. TLD chips (surface area 3.17 x 3.17 cm2) of three different thicknesses (0.230, 0.099, and 0.038 g/cm2) were used to extrapolate dose readings to an infinitesimally thin layer of LiF. This surface dose was measured for field sizes ranging from 1 x 1 cm2 to 40 x 40 cm2. The surface dose relative to maximum dose was found to be 10.0% for a field size of 5 x 5 cm2, 16.3% for 10 x 10 cm2, and 26.9% for 20 x 20 cm2. Using a 6-mm Perspex block tray in the beam increased the surface dose in these fields to 10.7%, 17.7%, and 34.2% respectively. Due to the small size of the TLD chips, TLD extrapolation is applicable also for intracavity and exit dose determinations. The technique used for in vivo dosimetry could provide clinicians information about the build up of dose up to 1-mm depth in addition to an extrapolated surface dose measurement. PMID- 8350823 TI - A technique for the evaluation of a missing tissue compensator system. AB - A two dimensional approach to the evaluation of a missing tissue compensator system has been developed and implemented. Quantitative descriptors of the dose area histograms generated by scanning films irradiated under a variety of compensated and uncompensated conditions are proposed. The method has been found to be useful during the acceptance testing of a commercial compensator system and the results of this exercise are presented. PMID- 8350825 TI - On the cause of the variation in tissue-maximum ratio values with source-to detector distance. AB - While tissue-maximum ratios (TMR) for 60cobalt treatment units have been shown to be independent of source-to-axis distance (SAD), high-energy photon beams demonstrate variations in their TMR as a function of SAD. Some authors have asserted that the distance dependence of the TMR stems from electron contamination in the beams, while others have suggested low-energy, scattered photons as the cause. Using a magnet to sweep contaminant electrons out of the photon treatment beam eliminates any variation in TMR with distance. Thus, electron contamination accounts for all of the distance dependence, and any low energy, scattered photons behave indistinguishably like the high-energy photons. PMID- 8350824 TI - Characteristics of a spoiled 6-MV beam from a dual-energy linear accelerator. AB - A beam spoiler for a 6-MV x-ray beam was designed and spoiled beam dosimetry performed. The spoiled beam quality was similar to that of the unspoiled beam. The percentage depth doses at 5 mm were at least 90% for all field sizes except 4 x 4 cm, while the surface dose at 0 mm varied from 22.5% for a 4 x 4-cm field to 85.8% for a 22 x 22-cm field. The spoiled beam showed degraded beam flatness for small field size at superficial depths; the beam flatness at 6 mm for a 4 x 4-cm field was +/- 9.0%. The beam flatness improved as the field size increased, e.g., at same depth, the beam flatness was +/- 2.5% for a 22 x 22-cm field. The penumbra width (90%-10%) of the spoiled beam was greater than that of the unspoiled beam for all field sizes and at all depths; e.g., at 0-mm depth, for a 22 x 22-cm field, the penumbra width was 3.8 cm for the unspoiled beam and 7.2 cm for the spoiled beam. Beyond dmax the difference in the penumbra widths between the spoiled and unspoiled beam was about 3-4 mm for all field sizes and at all depths. The peripheral dose was larger for the spoiled beam. PMID- 8350826 TI - Thermoluminescent characteristics of LiF:Mg,Ti from three manufacturers. AB - LiF:Mg,Ti thermoluminescent dosimeters (TLD's) were obtained from three manufacturers with the specification that they all lie within +/- 5% of the mean. All were chips of size 3 mm x 3 mm x 1 mm. The three sample groups were compared on the basis of their energy response, linearity of the thermoluminescent (TL) response with increasing exposure, sensitivity, and reproducibility of TL response. All TLD groups showed similar characteristics in energy response and linearity. This is to be expected since the base material and dopants were the same. However, the sensitivity varied among the three groups by as much as 40% and reproducibility measurements gave standard deviations ranging from 7% to 14% among the groups. Annealing procedures were identical in all cases, as were irradiation and readout conditions. PMID- 8350827 TI - An equivalent-square formula for head-scatter factors. AB - A simple formula is evaluated for calculating the equivalent square collimator setting that gives the same headscatter factor as a given rectangular field. The expression requires that one parameter is determined experimentally. It is found that one single value of this parameter can be used for the six x-ray beams studied (two accelerators, two energies, with and without wedge). PMID- 8350828 TI - Application of a commercial solid-water plane-parallel ionization chamber to the AAPM TG-21 protocol. PMID- 8350829 TI - Comments on the experimental determination of the replacement correction factor for parallel-plate ionization chambers in high-energy electron beams. PMID- 8350830 TI - Comments on the experimental determination of the polarity effect of two parallel plate ionization chambers in high-energy electron beams. PMID- 8350832 TI - Dose-volume histogram computations for small intracranial volumes. AB - A sampling formalism is presented to accurately compute the absolute volumes and integral dose-volume histograms of small volumes treated in stereotactic radiosurgery. The presence of small volumes and sharp dose gradients places special constraints on the computational formalism and the accuracy required to compute the dose-volume relationships. We use a spatially nonuniform random sampling method to allow an efficient and accurate computation of the dose-volume histograms for an arbitrary number of volumes. The computation of absolute volume vs dose allows intercomparison of dose delivered to target and dose-critical volumes and allows a quantitative trade-off analysis often critical to an optimal treatment of the lesion. PMID- 8350831 TI - Calculation of beta dosimetry in radiation synovectomy using Monte Carlo simulation (EGS4). AB - Using the EGS4 Monte Carlo code, absorbed dose rate factors were estimated for four radionuclides of interest in radiation synovectomy, an intra-articular radiation therapy to treat rheumatoid arthritis. The treatment consists of the injection of a beta-emitting radionuclide into the joint capsule in order to eliminate diseased synovium through irradiation. The radionuclides investigated are 32P, 90Y, 165Dy, and 198Au. Calculations reveal the absorbed dose factor (cGy cm2/MBq s) as a function of distance (mm) in an EGS4 model of the rheumatic joint. The model incorporates bone, articular cartilage, joint capsule, and tissue (synovium) components found in all synovial joints, with dimensions in the model corresponding to dimensions typically found in larger joints, e.g., the knee, shoulder, or hip. Results are compared with previous, analytical approaches to beta dosimetry in radiation synovectomy. In addition, radiation backscatter due to the presence of bone is investigated and determined to have a negligible enhancement effect on absorbed dose to synovium. PMID- 8350833 TI - Buildup region of high-energy x-ray beams in radiosurgery. AB - The depths of dose maxima of radiosurgical x-ray beams increase with the field diameter in the range from 10-30 mm. Furthermore, the degree of the increase is proportional to the photon beam energy. This behavior is in contrast to that of large radiotherapeutic fields, where the depths of dose maxima decrease with increasing field size. The surface doses, depths of dose maxima, and collimator scatter factors for radiosurgical beams with energies between 6 and 18 MV are presented. It is shown that the change in dmax for radiosurgical beams is a result of photon scatter in the phantom rather than in the collimator. Monte Carlo simulations of the radiosurgical beams are used to separate the total dose into two components: the primary dose and the scattered dose. Calculations indicate that buildup region characteristics are governed by the primary dose deposition in the medium. The scattered dose has a minimal effect on the total dose deposited in media by radiosurgical beams. PMID- 8350834 TI - Dosimetry of 125I sources in a low-density material using scaling. AB - One may apply O'Connor's scaling theorem to dose measurements with brachytherapy sources in order to overcome the difficulties associated with the need for high spatial accuracy. This possibility has been evaluated by measuring the dose distribution around 125I sources in a low-density styrofoam phantom and comparing it with the dose distributions in water and solid water. Some generalization of the scaling theorem is proposed to allow for the minor differences in atomic composition between styrofoam and water, and the distances are scaled according to the ratio of the linear attenuation coefficients, instead of the physical densities, of the two media. The validity of this application of the scaling theorem has also been tested using Monte Carlo calculations. The results indicate that the scaling of the styrofoam measurements to water is a useful approximation in brachytherapy dosimetry. PMID- 8350835 TI - Tumor localization using fundus view photography for episcleral plaque therapy. AB - The accurate localization of ophthalmic tumors on the scleral surface is important when calculating radiation dose to the tumor and adjacent structures from episcleral I-125 plaques. This is particularly true for tumors close to the fovea or optic nerve. A fundus view diagram of the eye is often used by ophthalmologists to describe the size and shape of the tumor perimeter as well as its geographical location on the retinal surface. There is, however, an inherent inaccuracy associated with the use of a hand drawn diagram to obtain physical measurements. A computer planning program has been developed which uses CT and a digitized photographic montage of the posterior hemisphere to estimate the size and location of posteriorly located tumors. A simple phantom was constructed to test the software and a direct comparison made between planned versus measured tumor size and location in an excised eye. PMID- 8350836 TI - Comments on dose measurements for a narrow beam in radiosurgery. PMID- 8350837 TI - Superheated drop detector for determination of neutron dose equivalent to patients undergoing high-energy x-ray and electron radiotherapy. AB - The superheated drop detector (SDD) consists of thousands of superheated drops dispersed in a small vial of gel, which vaporize upon exposure to high LET radiation, thereby providing a directly observable indication of neutron dose. This detector possesses high sensitivity to neutrons and insensitivity to high energy photons and electrons, making it suitable for the determination of neutron dose equivalent rates around high-energy photon and electron radiotherapy beams. In the present work, the SDD was used to measure the neutron dose equivalent in and around the radiotherapy beams produced by a 32-MeV linear accelerator. For both x-ray and electron beams, the neutron dose profiles were observed to follow the photon/electron radiotherapy beam profiles. For 25-MV x rays, the neutron dose equivalent per photon dose on the central axis increased by a factor of about 3 as field size increased from 5 x 5 to 30 x 30 cm. However, the neutron dose equivalent rate at 50 cm off-axis in the patient plane was essentially independent of field size. The neutron dose equivalent per electron dose was essentially zero for electron beams with energies below 15 MeV, but increased rapidly above 15 MeV. For 25-MeV electrons, neutron dose equivalent on the central axis was about 1/5 that for 25-MV x rays. Analogous to the data for 25-MV x rays, the neutron dose equivalent rate on the central axis of a 25-MeV electron beam exhibited a similar field size dependence and outside the beam it was essentially independent of field size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350838 TI - A survey of fluoroscopic exposure rates: AAPM Task Group No. 11 Report. AB - Fluoroscopic procedures, in general, result in much higher exposures to patients than do most types of radiographic procedures [National Council on Radiation Protection, Report 100, p. 31 (1989)]. In spite of this, fluoroscopic exposure rates can vary widely between systems, and often for no apparent reason. The charge of AAPM Task Group No. 11 was to evaluate fluoroscopic exposure rates at the entrant surface of the x-ray image intensifier, and to disseminate this information so that medical physicists could compare their own exposure rate measurements with typical values. The measurement protocol was defined for various system configurations. Sheets of copper were used to attenuate the x-ray beam, and the input exposure rate at the image intensifier (at the input mode closest to 23-cm diameter) in the absence of a scattering medium was determined. With 2 mm of copper as x-ray beam filtration, the median fluoroscopic exposure rate at the image intensifier was found to be 16.5 nC/kg/s (64.0 microR/s), with an average kV of 77 and mA of 2.0 (n = 62). PMID- 8350839 TI - Measurement of absolute blood iodine concentration during digital subtraction ventriculography. AB - A system to measure the absolute iodine concentration (mg iodine/milliliter blood) in the left ventricle (LV) during digital subtraction ventriculography has been developed. The technique uses a catheter to draw blood from the LV through a detection cell. This occurs as the iodine bolus passes through the heart. The cell determines iodine concentration by measuring x-ray attenuation as the iodinated blood passes between a low-power x-ray tube and a diode detector. In vitro and in vivo testing of the system was conducted. The system response was linear (r = 0.99) with respect to iodine concentration. This response was independent of hematocrit. Dispersion of contrast medium in the catheter caused distortion of the shape of the time-concentration curve. The impulse response of the system was measured and found to be independent of hematocrit. A correction algorithm based on Wiener filter deconvolution was developed. In vitro testing using simulated time-concentration curves demonstrated that the rms error in the iodine measurement after dispersion correction did not exceed 4% over the region of the time-concentration curve extending from the peak to the point on the tail where the signal fell to 50% of its peak value. Cardiac output was measured from the time-concentration curve via the indicator-dilution method in an animal model. This cardiac output measurement (COI) agreed closely with cardiac output measured simultaneously with an aortic flow probe (CO(P)), namely, COI = 1.02 CO(P)-0.03 L/min, r = 0.95, SEE = 10%, p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350840 TI - Comparison of ROC and AFC methods in a visual detection task. AB - The visual observer performance for detecting low-contrast patterns by employing both the receiver operating characteristic (ROC) and the 9-alternative forced choice (9-AFC) method is investigated. For each observer and each experimental technique, the results were reproducible with respect to a repeated observation. When the results of different observers for each method are compared, a strong variation of values is found. From the ROC data obtained, the expected percentages of correct detection in a 9-AFC experiment is calculated and compared with the corresponding values of the actual 9-AFC experiment. For some observers, the latter values were significantly higher than the computed ones, whereas for others the results showed good agreement with predictions from theory. PMID- 8350841 TI - Patient dose and image quality in five standard x-ray examinations. AB - Patient doses and image quality in five standard x-ray examination projections (22-36 measurements per each projection) have been measured, using homogeneous phantoms. The means and range of variation for the entrance skin air kerma values were: abdomen AP 5.2 mGy (1.1-21 mGy), chest PA 0.27 mGy (0.035-0.84 mGy), lumbar spine AP 8.4 mGy (2.9-28 mGy), skull LAT 3.1 mGy (1.1-7.7 mGy), and thoracic spine AP 7.9 mGy (1.3-22 mGy). Considerable variation was found in image quality parameters: film optical densities, image contrasts, and resolutions as well as in exposure values, tube voltages, exposure times, and in half-value thicknesses. The study indicated the need to standardize medical x-ray examination techniques in different x-ray departments. The measuring method can be used for comparing the patient dose and image quality of an individual x-ray unit to the doses and image quality in general use. The results can be used as the reference values for quality control of x-ray equipment. PMID- 8350842 TI - Evaluation of mammographic viewbox luminance, illuminance, and color. AB - Twenty-three viewboxes were evaluated in six mammography facilities. Luminance and illuminance measurements were made with a recently calibrated photometer. Color temperatures were measured with a Minolta color meter. The average luminance for the 23 viewboxes was 2920 nit (lumen/Sr/m2), the lowest value was 1610 nit, and the highest value was 3630 nit. The average illuminance was 40 lux (lumen/m2), with 6 lux as the lowest value, and 97 lux as the highest. The average color temperature was 8400 K with the lowest value of 4900 K, and the highest of 10,900 K. PMID- 8350843 TI - The evaluation of a clinical thermometer for measuring developer temperature in automatic film processors. AB - In medical imaging, the temperature of the developer solution in the film processor affects film speed (radiation dose), film contrast, and film base plus fog. The National Council on Radiation Protection and Measurement (NCRP) Report 99 on Quality Assurance, and the American College of Radiology (ACR) Mammography Quality Control Manual for Radiologic Technologists, indicate that the developer temperature should be within +/- 0.5 degree F (+/- 0.3 degree C) of that recommended by the manufacturer for the specific film/developer combination being used. The accuracy and repeatability of the thermometer is most important. This paper describes the requirements of a thermometer for measuring the temperature of the developer solution and suggests an inexpensive but accurate device for doing so. PMID- 8350844 TI - Adenosine administration for neonatal SVT. AB - Adenosine is a purine nucleoside that impairs conduction through the AV node and is thus effective in terminating tachycardias involving the AV node. Gaining acceptance as the drug of choice for neonatal supraventricular tachycardia (SVT), it is given IV as a rapid bolus with an initial dose of 0.05 mg/kg and can be increased in increments of 0.05 mg/kg every one to two minutes until termination of SVT (to a maximum of 0.25 mg/kg). Because of its half-life of 0.6 to 10 seconds, adenosine will not prevent reinitiation of SVT, therefore other medications should be considered if prophylaxis is required. An advantage of the short half-life is the transient nature of adverse effects, which can include flushing, nondistressing alterations in respiratory pattern, irritability, sinus bradycardia, and varying degrees of AV block. Administration to critically ill infants, including those requiring mechanical ventilation, has been reported. The infant's blood pressure, electrocardiogram, respiratory status, and capillary refill should be monitored before, during, and after adenosine administration. PMID- 8350845 TI - The effects of a pressure relief mattress on postnatal head molding in very low birth weight infants. AB - Very low birth weight (VLBW) infants often develop postnatal head molding (PHM)- an elongation of the skull--when a standard, firm mattress is used. This study was undertaken to determine if a pressure relief mattress (PRM) might reduce the severity of PHM. One hundred twenty-eight infants (birth weight range 567-1,490 gm, mean 1,084; gestational age range 24-36 weeks, mean 28.5) with no congenital or acquired anomalies affecting head growth were randomly assigned to a control group (standard, firm mattress) or a study group (PRM). Study infants were placed on the PRM within 72 hours of birth. Occipitofrontal circumference (OFC) and anterior-posterior (AP) and biparietal (BP) diameters were measured at day four, seven, and then at one week intervals of life until the infant reached 2,000 gm or was discharged. An electronic digital caliper with an accuracy of 0.025 mm was used to obtain the AP and BP measurements. T-tests revealed no significant differences in head shape between the two groups. In conclusion, the pressure relief mattress did not reduce PHM in VLBW infants. PMID- 8350846 TI - Perinatal grief: response to the loss of an infant. AB - The grief response of parents following loss of an infant from a multiple gestation pregnancy was explored to describe the experience, compare and contrast mother's and father's responses, and analyze the properties of the Perinatal Grief Scale. Twenty-seven parents participated. Parental responses were complex and variable. Most parents disagreed with experiencing difficulty coping and despair. Confrontive, self reliant, and supportant coping strategies were used most frequently, while supportant, confrontive and optimistic strategies were reported the most effective. Anxiety, depression and alterations in activities of daily living were reported. The total impact of life events was slightly positive for this group. Although the instruments were reliable in this population of parents, sensitivity was reduced. A model of grief associated with multiple gestation perinatal loss was generated. Selection and effectiveness of coping strategies appear to be not only interrelated, but dependent on the time since the infants death and the length of the infants life. The length of an infant's life and time since death were affirmed as related to both the strength and type of relationship between variables associated with the grief response and to use and effectiveness of coping strategies. Responses of mothers and fathers appear to be similar. PMID- 8350847 TI - Comparison of percutaneous venous catheters and teflon catheters for intravenous therapy in neonates. AB - The purpose of this study was to compare the average duration of catheterization of percutaneous venous catheters (PVCs) with Teflon catheters placed in peripheral veins of neonates, and to describe the incidence of mechanical or infectious complications associated with their use. The sample consisted of twelve subjects with a total of 52 catheters--17 PVCs and 35 Teflon catheters. The results of the study indicated both a significant increase in the duration of catheterization (p = .001) and a significant reduction in the incidence of complications (p = .004) when PVCs were used. The mean duration of catheterization for PVCs was 178.6 hours and for Teflon catheters 41.9 hours. Although 80.8 percent of all the neonates studied suffered some complication leading to early catheter removal, such complications were observed most frequently with Teflon catheters (91 versus 59 percent of PVCs). However, the one subject who experienced the complication of catheter-related sepsis did have a PVC in situ for 313.5 hours. For this sample of neonates, the PVC was the most efficacious mode of IV therapy. PMID- 8350848 TI - Advocacy in action. AB - This article uses a paradigm case from clinical practice to isolate an abstract nursing concept. After identifying the concept, active advocacy, the article first defines it and then analyzes it in depth. The purpose of the article is to show how understanding abstract nursing concepts contributes to greater insight into the nuances of providing bedside care and contributes to the development of expert clinical practice. The article demonstrates how nurses in clinical practice can relate their own paradigm cases to other nurses as a way of sharing knowledge and information. PMID- 8350849 TI - Proctor & Gamble. PMID- 8350851 TI - Puzzles as learning tools. PMID- 8350850 TI - Kangaroo care. PMID- 8350852 TI - Procedural flow chart job aid for the exchange transfusion. PMID- 8350853 TI - Hepatitis B vaccine. PMID- 8350854 TI - The effect of environmental lighting on the oxygen saturation of preterm infants in the NICU. AB - The premature infant is more vulnerable to the NICU environment than a full-term infant due to neurologic immaturity and physiologic instability. Studies have been done on the effects of long-term decreases in environmental light, but none have been done on the immediate effects. The purpose of this study was to determine the relationship between immediate changes in environmental illumination and oxygen saturation in preterm neonates and whether these were affected by gestational and postnatal age. The oxygen saturations of 27 sleeping infants (2 to 56 days of age) between 26 and 37 weeks gestation were continuously recorded for 40 minutes utilizing a Nellcor N200 oximeter. After recording baseline saturations for 5 minutes with the room lights at 100 footcandles, the illumination level was lowered to 5 footcandles. At the end of 30 minutes, lights were increased to the previous level. Oxygen saturations were recorded at one and five minutes after illumination decreases and increases. There was a statistically significant interaction between repeated measures of saturation at baseline and one and five minutes after lights were increased and covariates gestational, corrected gestational, and postnatal age (p = .02, p = .008, p = .005). Repeated measure analysis of covariance (ANCOVA) revealed no statistically significant changes in oxygen saturations after the lights had been lowered for babies who were younger in gestational or postnatal age. The results of this study suggest that rapidly increasing illumination may be a cause of stress to the younger gestationally and postnatally preterm neonate. PMID- 8350855 TI - Jin bu huan toxicity in children--Colorado, 1993. AB - The consumption of traditional ethnic remedies can have adverse health effects, especially among children. Life-threatening bradycardia with rapid onset and central nervous system (CNS) and respiratory depression developed in three unrelated children in Colorado during 1993 following ingestion of Jin Bu Huan tablets, a Chinese herbal medicine used for relieving pain. This report summarizes the investigations of these cases. PMID- 8350856 TI - Surveillance for cholera--Cochabamba Department, Bolivia, January-June 1992. PMID- 8350857 TI - Cigarette smoking-attributable mortality and years of potential life lost--United States, 1990. AB - Cigarette smoking is the single most preventable cause of premature death in the United States. An estimated 390,000 smoking-attributable deaths in the United States occurred in 1985, and more than 434,000 deaths occurred in 1988; in 1988, an estimated 1,198,887 years of potential life lost (YPLL) before age 65 were attributed to smoking. To estimate the national impact of cigarette smoking on mortality and YPLL, calculations were performed using the Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC) software. This report summarizes the results of this analysis. PMID- 8350858 TI - Public health consequences of a flood disaster--Iowa, 1993. AB - Unprecedented amounts of rain in the spring and summer of 1993 led to disastrous flooding and crop damage in nine Midwestern states. In Iowa (1990 population: 2,777,000), extensive flood damage occurred in all 99 countries. On July 11, 1993, the Iowa Department of Public Health (IDPH) requested assistance from CDC to assess the adverse public health impact of the flooding and to plan the public health response to the disaster. CDC assisted IDPH in performing an initial rapid statewide public health assessment and establishing weekly surveillance to monitor ongoing or anticipated flood-related health problems. This report summarizes the methods of the assessment and surveillance and preliminary findings. PMID- 8350859 TI - Tuberculosis in Philippine National World War II Veterans immigrating to Hawaii, 1992-1993. AB - The Immigration Act of 1990* allows World War II veterans who are Philippine nationals to be naturalized as U.S. citizens and to enter the United States without any medical screening or restrictions. Following the diagnosis of tuberculosis (TB) in February 1992 in a Philippine national veteran who had recently arrived in Hawaii, the Hawaii Department of Health (HDOH) initiated efforts to assist veterans who had already arrived in Hawaii to receive TB testing and appropriate treatment and monitoring. This report describes the first case of TB identified in a veteran who entered Hawaii from the Philippines under this act and summarizes efforts by HDOH to detect and treat TB among Philippine national veterans. PMID- 8350860 TI - State-specific changes in cholesterol screening--behavioral risk factor surveillance system, 1988-1991. AB - High blood cholesterol (HBC) is an important risk factor for coronary heart disease (1)--the leading cause of death in the United States. To reduce the prevalence of elevated cholesterol levels in the United States, in 1985 the National Heart, Lung, and Blood Institute initiated the National Cholesterol Education Program (NCEP). The NCEP recommends that all adults aged > or = 20 years be screened for HBC at least once every 5 years. One of the national health objectives for the year 2000 is to increase to 75% the percentage of adults screened for HBC within the preceding 5 years (objective 15.14). To measure progress toward this objective, data from CDC's Behavioral Risk Factor Surveillance System (BRFSS) were used to examine state-specific trends in cholesterol screening from 1988 through 1991. This report summarizes the results of this analysis and provides a projected estimate of the 1994 screening rates for HBC in each state. PMID- 8350861 TI - Control of glycolytic enzyme binding: effect of changing enzyme substrate concentrations on in vivo enzyme distributions. AB - The effect of changing concentrations of glycolytic intermediates on the binding of phosphofructokinase, aldolase and pyruvate kinase to cellular particulate matter was investigated. Concentrations of glycolytic intermediates were altered by adding 2 mM iodoacetic acid (IAA) to an incubation medium containing tissues isolated from the channelled whelk Busycon canaliculatum. Iodoacetic acid inhibited glyceraldehyde 3-phosphate dehydrogenase activity causing a 100-400 fold increase in the concentration of fructose 1,6-bisphosphate as well as 3-20 fold increases in glucose 6-phosphate, fructose 6-phosphate, and dihydroxyacetone phosphate levels depending on the experimental protocol. Cellular pH values were not statistically different in the presence of IAA. Measurement of enzyme binding to particulate matter showed that the binding of phosphofructokinase, aldolase and pyruvate kinase was unaffected by iodoacetic acid under any experimental condition. These results show that changes in the tissue concentrations of enzyme substrates and products do not regulate enzyme binding to particulate matter in the cell. PMID- 8350862 TI - Kinetic study of the cytotoxic effect of alpha-sarcin, a ribosome inactivating protein from Aspergillus giganteus, on tumour cell lines: protein biosynthesis inhibition and cell binding. AB - alpha-Sarcin is a ribosome inactivating protein produced by the mould Aspergillus giganteus. The effect of this protein on eight different tumour cell lines has been studied in the absence of any agent affecting membrane permeability. The protein is cytotoxic for all the tumour cell lines considered. alpha-Sarcin modifies the cell proliferation pattern by inhibiting the protein biosynthesis of the cultured cells. No membrane damage produced by alpha-sarcin has been observed by measuring lactic dehydrogenase leakage. Alteration on the cell mitochondrial activity has not been detected upon treatment with alpha-sarcin. Differences on the extent of the protein binding to the cells have been observed by flow cytometric measurements. The kinetic analysis of the protein biosynthesis inhibition produced by alpha-sarcin reveals an alpha-sarcin concentration dependent lag phase followed by a first order decrease of the protein synthesis rate. This parameter is dependent on the external alpha-sarcin concentration. A saturable component for the action of alpha-sarcin is also deduced from these experiments. Results are discussed in terms of the protein passage across the cell membrane as the potential rate-limiting step for the action of alpha-sarcin. PMID- 8350863 TI - Effects of saturated fatty acids on n-6 fatty acid metabolism in cultured human monocyte-like cells (U937). AB - Effects of supplementation of saturated fatty acids (16:0 and 18:0) on metabolism of the cytotoxic n-6 fatty acids in cultured human monocyte-like cells (U937) have been examined. U937 cells were incubated in 5% delipidated fetal bovine serum containing 16:0 and 18:0. Supplementation of either 16:0 or 18:0 has no significant effect on the uptake of 18:2n-6 and 18:3n-6. However, addition of 16:0 to the medium increased whereas 18:0 suppressed the cytotoxic effects of 18:2n-6 and 18:3n-6. In addition, 16:0 supplementation reduced the incorporation of n-6 fatty acids in cellular phospholipid fraction, and enhanced the metabolism of n-6 fatty acids, particularly the conversion of 20:3n-6 to 20:4n-6 in U937 cells. Results with microsomes prepared from U937 cells also showed that 16:0 supplementation increased the delta 5 desaturase activity. This may be related in part to an increase in the availability of 20:3n-6, since results obtained in a separate study have shown that 16:0 competed with 20:3n-6 for incorporation into the phospholipid molecule at sn-2 position. Increasing the availability and formation of long chain n-6 fatty acids, which are cytotoxic, might also be responsible for increasing cytotoxicity of 16:0 supplementation. PMID- 8350864 TI - Stimulatory effect of beta-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells. AB - The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in osteoblastic MC3T3-E1 cells. Cells were cultured for 3 days at 37 degrees C in a CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further for appropriate periods of time. The presence of AHZ (10(-7)-10(-5) M) stimulated the proliferation of cells. AHZ (10(-6) and 10(-5) M) increased deoxyribonucleic acid (DNA) content in the cells with 48 hr-culture. This increase was completely blocked by the presence of cycloheximide (10(-6) M) or hydroxyurea (10(-3) M). Also, the presence of cycloheximide (10(-6) M) completely inhibited the AHZ (10(-5) M)-induced increase in the proliferation of cells. Meanwhile, parathyroid hormone (10(-7) M), estrogen (10(-9) M) and insulin (10( 8) M) significantly increased cellular DNA content. However, these hormonal effects clearly lowered in comparison with that of AHZ (10(-5) M). Dibutyryl cyclic AMP (10(-4) M) and zinc sulfate (10(-5) M) did not cause a significant increase in cellular DNA content. The present results support the view that AHZ has a direct specific proliferative effect on osteoblastic cells in vitro and that this effect is dependent on protein synthesis. PMID- 8350865 TI - Tissue concentration of calcium-binding protein regucalcin in rats by enzyme linked immunoadsorbent assay. AB - The concentration of calcium-binding protein regucalcin in the tissues of rats was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti regucalcin IgG. In male rats (5 weeks old), regucalcin was most pronounced in the liver. Liver regulcalcin concentration was about 0.1 microM, when it was calculated with regucalcin molecular weight of 28,800. The relatively higher level of regucalcin was also found in the kidney as compared with that of the skeletal muscle, duodenum, testis, lung, heart, spleen, cerebral cortex and hippocampus. Similarly in female rats, regucalcin was remarkable in the liver, and appeared only slightly in the kidney. Thus, the tissue distribution of regucalcin in rats was specific in the liver. The concentration of regucalcin in the liver was altered with increasing age of rats; liver regucalcin level linearly increased during 5 weeks old after birth of male rats, and then began to decrease gradually. The results coincided with the previous observation of Northern blot analyses by using liver regucalcin cDNA as a probe. The present finding clearly demonstrates that regucalcin is specifically synthesized in the liver of rats. PMID- 8350866 TI - Effects of vanadate administration on the high sucrose diet-induced aberrations in normal rats. AB - Effects of feeding sucrose rich diet supplemented with and without the insulinmimetic agent vanadate for a period of six weeks were studied in rats. Sucrose diet caused hypertriglyceridemia (140% increase), hyperinsulinemia (120% increase) and significant elevations in the levels of glucose (p < 0.001) and cholesterol (p < 0.05) in plasma as compared to control starch fed rats. Activities of hepatic lipogenic enzymes, ATP-citrate lyase, glucose 6-phosphate dehydrogenase and malic enzyme increased by 100-150% as a result of sucrose feeding. However, glycogen content and the activities of glycogen synthase and phosphorylase in liver remained unaltered in these animals. The plasma levels of triacylglycerols and insulin in the rats fed on vanadate supplemented sucrose diet were 65% and 85% less, respectively as compared to rats on sucrose diet without vanadate. The concentrations of glucose and cholesterol in plasma and the activities of lipogenic enzymes in liver did not show any elevation in sucrose fed rats when supplemented with vanadate. These data indicate that the sucrose diet-induced metabolic aberrations can be prevented by the insulin-mimetic agent, vanadate. PMID- 8350867 TI - Effects of high sucrose diet on insulin-like effects of vanadate in diabetic rats. AB - The insulin-like effects of vanadate were compared in streptozotocin-induced diabetic rats fed on high starch control and high sucrose diets for a period of six weeks. Diabetic rats in both diet groups were characterized by hypoinsulinemia, hyperglycemia (6.8-7.0 fold increase) and significant decreases (p < 0.001) in the activities of glycogen synthase, phosphorylase and lipogenic enzymes, ATP-citrate lyase, glucose 6-phosphate dehydrogenase and malic enzyme in liver. There were no diet-dependent differences in these abnormalities. However, the insulin-mimetic agent vanadate was more effective in diabetic rats fed sucrose diet as compared to animals fed control starch diet. Vanadate administration resulted in 30% and 64% decreases in plasma glucose levels in diabetic rats fed control and sucrose diets, respectively. The activities of glycogen synthase (active) and phosphorylase (active and total) were restored significantly by vanadate in control (p < 0.05-0.01) and sucrose (p < 0.001) diets fed diabetic rats. This insulin-mimetic agent increased the activities of hepatic lipogenic enzymes in control diet fed rats to 38-47% of normal levels whereas in sucrose fed group it completely restored the activities. Sucrose diet caused a distinct effect on the plasma levels of triacylglycerol (4-fold increase) and apolipoprotein B (2.8-fold increase) in diabetic rats and vanadate supplementation decreased their levels by 65-75%. These data indicate that vanadate exerts insulin-like effects in diabetic rats more effectively in sucrose fed group than the animals fed control diet. In addition, vanadate also prevents sucrose-induced hypertriglyceridemia. PMID- 8350868 TI - Induction of N-acetylglucosaminyltransferase V by elevated expression of activated or proto-Ha-ras oncogenes. AB - Viral infection of cultured cells with transforming viruses causes an increase in cell-surface N-linked beta 1-6 (GlcNAc beta 1-6Man) branching of complex-type oligosaccharides. Similar observations have been made after transfection of cells with activated oncogenes, which is associated with an induction of tumorigenic and metastatic properties. In this study, the effects of transfection of both activated and proto-Ha-ras oncogenes into NIH3T3 cells were analyzed. The results showed that, in comparison with NIH3T3 cells, both ras transfectants have increased sensitivity to the cytotoxic action of L-PHA. An increase in beta 1-6 branching and an increased level of N-acetylglucosaminyltransferase V (GlcNAc-T V), the enzyme which initiates the beta 1-6 branching were also observed. The levels of GlcNAc-T I and beta 1-4 Gal-T remained unchanged in activated Ha-ras transfected NIH3T3 cells. These data suggest that a specific induction of GlcNAc T V occurs after transfection with either the proto- or activated Ha-ras oncogenes, which is responsible for the increased beta 1-6 branching previously observed. PMID- 8350869 TI - Role of protein kinase C in oxidant--mediated activation of phospholipase A2 in rabbit pulmonary arterial smooth muscle cells. AB - The present study was undertaken to test the hypothesis that activation of cell membrane associated protein kinase C (PKC) plays a role in stimulating cell membrane associated phospholipase A2 (PLA2) activity, and subsequent liberation of arachidonic acid (AA) under exposure of rabbit pulmonary arterial smooth muscle cells to the oxidant hydrogen peroxide (H2O2). Exposure of the smooth muscle cells to H2O2 dose-dependently stimulates [14C] AA release, and enhances the cell membrane associated PLA2 activity. Pretreatment of the cells with protein kinase C (PKC) inhibitors H7 and sphingosine prevent the cell membrane associated PLA2 activity, and AA release caused by H2O2. Treatment of the smooth muscle cells with H2O2 stimulates the cell membrane associated PKC activity. Pretreatment of the cells with an antioxidant vitamin E prevents H2O2 caused stimulation of the cell membrane associated PKC activity. The cell membrane associated PLA2 and PKC activities correlate linearly. These results suggest that H2O2 caused stimulation of the smooth muscle cell membrane associated PLA2 activity, and subsequent liberation of AA can occur through an increase in the activity of the cell membrane associated PKC. PMID- 8350870 TI - Elicitation of distinct populations of monoclonal antibodies specific for the variable domains of monoclonal anti-fluorescein antibody 4-4-20. AB - Armenian hamsters were immunized with non-liganded, partially liganded or affinity-labeled anti-fluorescein Mab 4-4-20. Seventeen hybridoma producing monoclonal anti-4-4-20 antibodies were characterized from chemically-mediated fusions of immune hamster lymphocytes with murine Sp2/O-Ag14 myeloma cells. Distinct populations of anti-4-4-20 monoclonal antibodies were isolated from hamsters receiving immunizations with partially liganded Mab 4-4-20 relative to those receiving affinity-labeled 4-4-20. Two of the three monoclonal antibodies produced in response to partially liganded 4-4-20 were inhibited in their interaction with 4-4-20 by fluorescyl ligand. These two clones, 1F4 and 1B7, recognized unique epitopes on the 4-4-20 molecules, as demonstrated by non reactivity with members of the 4-4-20 idiotype family. Additionally, 1F4 and 1B7 demonstrated the ability to delay the association of fluorescein with Mab 4-4-20. The 14 characterized non-ligand-inhibitable Mabs elicited to affinity-labeled 4-4 20 were classified into four separate groups based on various binding properties with members of the 4-4-20 idiotype family and binding to resolved H- and L chains in a western blot. Members of three of the four groups showed strong reactivity with both 04-01 Ig and 04-01 SCA, which utilizes the same L-chain as Mab 4-4-20. Six non-ligand-inhibitable Mabs, 4A6, P1E11, 3A5-1, 2C3, 2C4, and 1A4, delayed the dissociation rate of ligand from Mab 4-4-20 and mutant 4-4-20 SCA L32phe. PMID- 8350871 TI - Defining the structural correlates responsible for loss of arsonate affinity in an IDCR antibody isolated from an autoimmune mouse. AB - Immunization of the autoimmune mouse strain (M x A) Id/lpr with Ars-KLH, has been shown to elicit a prolonged anti-Ars IdCR response similar to that found in A/J mice. Cell fusion of splenocytes from a diseased mouse previously immunized with Ars-KLH resulted in a monoclonal antibody, 1-52.30, that was found to express the strain A major cross-reactive idiotype, but failed to bind Ars. Nucleotide sequence analysis demonstrated that 1-52.30: (a) used the "canonical" combination of gene segments associated with this idiotype, and (b) exhibited a pattern of somatic mutation consistent with selection for high affinity Ars binding. Two amino acids, VL 91 and 93, were mutated in 36-65, the germline equivalent of the IdCR antibodies, to 1-52.30-like residues (91G-->D, 93T-->M). The results of the mutagenesis showed that changing a single light chain residue, VL 91, from glycine to aspartic acid, resulted in a dramatic loss of Ars binding activity. PMID- 8350872 TI - Recombination activating genes-1 and -2 of the rabbit: cloning and characterization of germline and expressed genes. AB - The recombination activating genes RAG-1 and RAG-2 appear to be necessary components of the machinery needed for the Ig or TCR gene rearrangements that occur in developing B and T lymphocytes. In addition RAG-2 has been implicated in the process of V-gene diversification by somatic gene conversion in the chicken. Because gene conversion may be an important mechanism for V-gene diversification in the rabbit, we cloned the rabbit RAG locus and characterized the coding regions of the genomic RAG-1 and RAG-2. In addition, we sequenced cDNAs encompassing the RAG-2 coding region, part of the RAG-2 5' untranslated region and a 967 bp fragment of cDNA from the RAG-1 coding region. Northern analysis revealed a RAG-1 mRNA of 6.6 kb which is similar in size to the RAG-1 mRNA reported previously for other species, and a major species of RAG-2 mRNA of 4.4 kb, which is larger than that from the mouse (2.2 kb). Analysis of the genomic clones showed that, as in other species, the RAG-1 and RAG-2 genes are oriented so as to be convergently transcribed. The DNA sequence analysis showed that the rabbit RAG-1 coding region is 91, 85 and 72% identical to human, mouse and chicken, respectively. The deduced RAG-1 protein sequence for rabbit is 93, 90 and 78% identical to human, mouse and chicken. Comparison of the rabbit RAG-2 coding region revealed 90, 87 and 71% identity to human, mouse and chicken, respectively, at the nucleotide level, and 91, 90 and 72% at the protein level. Although there is considerable conservation of sequence between species, we obtained evidence for allelic forms of the rabbit RAG locus both by Southern analyses and by sequencing. A remarkable degree of polymorphism was found in our rabbit colonies, particularly in the region 3' of the rabbit RAG-2 coding region. A 5' cDNA probe hybridized with one or more additional fragments that are not detected with the coding region probes, suggesting that the 5' cDNA sequence results from splicing of one or more upstream exons. PMID- 8350873 TI - Major involvement of cathepsin B in the intracellular proteolytic processing of exogenous IgGs in U937 cells. AB - Monoclonal antibodies used for diagnostic and therapeutic purposes behave as antigens when injected into patients. They are recognized by T cells in a processed form and in a major histocompatibility complex class II restricted fashion. Monoclonal murine IgG2a were used as a model to analyse the early phase of antigen processing in U937 cells. IgG2a prebound to cell surface Fc receptors were rapidly internalized in the cells. During internalization, they were proteolysed with a time-dependent intracellular accumulation of 26, 25, 24, 22 and 14 kDa fragments. Comparison of in vitro IgG2a proteolysis by U937 subcellular fractions or by purified cathepsin B and their intracellular processing indicated that a major cathepsin B like protease is responsible for IgG2a intracellular processing in endo-lysosomal compartments of U937 cells. PMID- 8350874 TI - Immobilized IL-2 preserves the viability of an IL-2 dependent cell line. AB - The mouse T-cell line CTLL-2 is known to be dependent on interleukin-2 (IL-2) for both growth and viability. These cells possess high affinity IL-2 receptors and have been shown to internalize IL-2 after binding. To determine if internalization of IL-2 is required for the mediation of its signal, IL-2 was covalently coupled to an insoluble matrix via glutaraldehyde cross-linking and CTLL-2 cells were incubated with the immobilized lymphokine matrix. This covalent cross-linking prevents the free lateral diffusion and internalization of the bound IL-2 receptors (IL-2R) while still permitting specific binding between the cells and the immobilized ligands. Although only very limited proliferation was observed during the incubation as assessed by 3H-thymidine incorporation, the viability of the CTLL-2 cells on the immobilized IL-2 matrix was preserved. Cells incubated on the immobilized IL-2 surface could proliferate in response to exogenous soluble IL-2 that was added to the cultures after 36 hours whereas control cultures incubated with an immobilized BSA matrix had died. This indicates that immobilized IL-2 can mediate some of the activity of soluble IL-2 and that internalization of the IL-2 receptor may not be required for at least part of the IL-2 mediated effect. PMID- 8350875 TI - Mu switch region deletion is associated with both T cell independent and T cell dependent responses. AB - Isotype switching is a process by which immunoglobulin variable gene regions initially proximal to and expressed with the mu constant region gene (C mu) can rearrange downstream to other constant region genes. Thus the same antigen binding site can be expressed with each of the other constant region isotypes and perform the full panoply of effector functions. Although isotype switching is thought to involve highly reiterated 'switch site' sequences located 5' to constant region genes, the exact role of these switch sites is unknown. It has been reported that prior to switching, the 'donor' switch site 5' of C mu occasionally undergoes deletions, but it is not known whether this is an adventitious event or one which predisposes to or prevents isotype switching. Since T cell independent (TI) immune responses are dominated by IgM while T cell dependent (TD) responses are associated with switching to IgG, we have examined the state of the mu switch site in 51 IgM-producing hybridomas isolated from a variety of TI and TD responses. Although more hybridomas from the TI responses studied exhibited S mu deletions, deletion of S mu also occurred in hybridomas isolated from TD responses. Analysis of a well-characterized clonally related subset of IgM hybridomas also revealed that mu switch region deletion can be associated with the productive allele. PMID- 8350876 TI - Nucleotide sequences of Abb mRNA in mutant mouse S-27 resisting cancer metastasis and affecting responses to tuberculosis. PMID- 8350877 TI - [PreS-sequence of the hepatitis B virus envelope: molecular biology and immunology]. AB - Current data on molecular biology and immunology of the proteins of hepatitis B viral capsid encoded by the preS-region of HBV genome are reviewed. Main attention is paid to study of the immune properties of the capsid proteins, to search of immune dominant epitopes encoded in preS-sequences. The medical and biological significance of the research is shown as exemplified by search of preS antigens and anti-preS-antibodies in serum from patients suffering hepatitis B. The use of preS-sequences as components of vaccine preparations is discussed. PMID- 8350879 TI - A method for isolation of sequences missing in one of two related genomes. AB - We describe a novel technique for isolation of sequences that are present in one genome (tracer), but absent in another (driver). Tracer DNA, cleaved with Sau 3A and capped with a single stranded PCR adapter, is allowed to hybridize with an excess of sheared biotinylated driver; biotinylated DNA and its hybrids with the tracer are removed by phenol/chloroform extraction after incubation with streptavidin. After several rounds of subtraction the ends of self-annealed tracer molecules from the nonextractable fraction are filled-in with Tag polymerase and amplified, using the single stranded PCR adapter as a primer. The method has been applied to purification of fragments from a 2.9 kb plasmid added to E. coli DNA at equimolar quantity. Plasmid derived fragments (250-1000 bp), initially comprising 1/1400th part of tracer DNA, were purified to homogeneity after two rounds of subtraction followed by PCR. PMID- 8350878 TI - [Isolation and properties of BstBSI restriction endonuclease from the thermophilic soil bacteria Bacillus stearothermophilus BS]. AB - A new restriction endonuclease BstBSI was isolated and purified from the thermophilic soil bacterium Bacillus stearothermophilus BS by the blue sepharose and hydroxyapatite chromatographies. The enzyme is an isoschizomer of SnaI from Sphaerotilus natans C. It recognizes the hexanucleotide GTATAC and cleaves DNA in the center of the sequence. The maximal catalytic activity of the endonuclease is registered in 50 mM tris-HCl (pH 9.0) buffer with the high ionic strength (100 mM NaCl) in the presence of 10 mM MgCl2 at 45 degrees C. Glucosylated DNA of the phage T4 is not cleaved by the enzyme. PMID- 8350880 TI - [HIV lipids--biological role and target for antiviral agents]. PMID- 8350881 TI - [Induction of synthesis of extracellular DNAase from Proteus mirabilis under the effect of compounds, blocking DNA replication]. AB - The effects of mitomycin C and nalidixic acid on the biosynthesis of extracellular endodeoxyribonuclease in Proteus mirabilis have been studied. The presence of both antibiotics in the periodic and short-time cultures of washed off cells has increased both the activity of the DNAse and protein yield in cultural liquid and bacterial cells. PAGE-electrophoresis has shown the effect of mitomycin C to increase or induce the synthesis a large number of Proteus mirabilis extracellular proteins. PMID- 8350882 TI - [Association of DNA with the nuclear skeleton]. AB - A significant functional role is ascribed to DNA association with the nuclear skeleton. Specific proteins tightly bound to DNA have been discovered. According to one point of view these proteins perform constant attachment of DNA to the nuclear matrix, however, according to other authors this complex exists in transcribed genes only. In proliferating cell DNA is anchored by DNA topoisomerase II and DNA-polymerase alpha. Except for proteins this function is performed by glycoproteins, neutral and phospholipids, RNA. Three types of specific DNA sequences have been elucidated: 1. AT-rich enhancers (SAR); 2. GC rich origins of replication; 3. centromere and satellite DNA. In places of binding to the nuclear matrix DNA bears the numerous defects of secondary structure. Based on different criteria several types of DNA complexes with nuclear matrix proteins are distinguished: 1. resistant (lamina) and sensitive (intramolecular fibrils) to chelating agents; 2. formed by transcriptional complexes (transitory) and origins of replication (constant); 3. tight (resistant to salt-urea solutions, formed by replicative complex proteins) and weak (sensitive). PMID- 8350883 TI - A two-year trial of oleic and erucic acids ("Lorenzo's oil") as treatment for adrenomyeloneuropathy. AB - BACKGROUND: Adrenomyeloneuropathy is an X-linked recessive disorder characterized by myelopathy, peripheral neuropathy, and cerebral demyelination, which develop in association with the accumulation of very-long-chain fatty acids. The administration of oleic and erucic acids inhibits the synthesis of very-long chain fatty acids. Recently such dietary treatment has been widely publicized as a possible cure for this disease. METHODS: We conducted an open trial in 14 men with adrenomyeloneuropathy, 5 symptomatic heterozygous women, and 5 boys (mean age, 13 years) with preclinical adrenomyeloneuropathy. The patients ate a low-fat diet and received daily doses of glycerol trioleate oil (1.7 g per kilogram of body weight) and glycerol trierucate oil (0.3 g per kilogram). Clinical manifestations, cerebral and spinal cord magnetic resonance imaging (MRI) scans, nerve conduction, and brain-stem auditory and somatosensory evoked potentials were studied prospectively over 18 to 48 months. Plasma levels of very-long-chain fatty acids and the side effects of erucic acid were monitored monthly. RESULTS: By week 10, plasma very-long-chain fatty acid levels declined nearly to normal. Nonetheless, over a mean follow-up of 33 months none of the 14 men with adrenomyeloneuropathy improved. In nine men there was functional deterioration, coincident in four with new cerebral lesions on MRI. In a single patient there was a reduction in cerebellar demyelination, but without clinical improvement. In one of the five asymptomatic boys signs of myelopathy developed. There were no changes in the symptomatic heterozygous women. There was some improvement in peroneal-nerve conduction, but no detectable clinical improvement. Conduction to the parietal cortex (T12-P37 interpeak latency) worsened in both the symptomatic men and the boys with preclinical adrenomyeloneuropathy. There was no change in other somatosensory evoked potentials or in brain-stem auditory evoked potentials. Asymptomatic thrombocytopenia (< 100,000 cells per cubic millimeter) was noted in six patients. CONCLUSIONS: In this open trial we found no evidence of a clinically relevant benefit from dietary treatment with oleic and erucic acids ("Lorenzo's oil") in patients with adrenomyeloneuropathy. PMID- 8350885 TI - A preliminary study of cardiopulmonary resuscitation by circumferential compression of the chest with use of a pneumatic vest. AB - BACKGROUND: More than 300,000 people die each year of cardiac arrest. Studies have shown that raising vascular pressures during cardiopulmonary resuscitation (CPR) can improve survival and that vascular pressures can be raised by increasing intrathoracic pressure. METHODS: To produce periodic increases in intrathoracic pressure, we developed a pneumatically cycled circumferential thoracic vest system and compared the results of the use of this system in CPR (vest CPR) with those of manual CPR. In phase 1 of the study, aortic and right atrial pressures were measured during both vest CPR (60 inflations per minute) and manual CPR in 15 patients in whom a mean (+/- SD) of 42 +/- 16 minutes of initial manual CPR had been unsuccessful. Vest CPR was also carried out on 14 other patients in whom pressure measurements were not made. In phase 2 of the study, short-term survival was assessed in 34 additional patients randomly assigned to undergo vest CPR (17 patients) or continued manual CPR (17 patients) after initial manual CPR (duration, 11 +/- 4 minutes) had been unsuccessful. RESULTS: In phase 1 of the study, vest CPR increased the peak aortic pressure from 78 +/- 26 mm Hg to 138 +/- 28 mm Hg (P < 0.001) and the coronary perfusion pressure from 15 +/- 8 mm Hg to 23 +/- 11 mm Hg (P < 0.003). Despite prolonged unsuccessful manual CPR, spontaneous circulation returned with vest CPR in 4 of the 29 patients. In phase 2 of the study, spontaneous circulation returned in 8 of the 17 patients who underwent vest CPR as compared with only 3 of the 17 patients who received continued manual CPR (P = 0.14). More patients in the vest CPR group than in the manual-CPR group were alive 6 hours after attempted resuscitation (6 of 17 vs. 1 of 17) and 24 hours after attempted resuscitation (3 of 17 vs. 1 of 17), but none survived to leave the hospital. CONCLUSIONS: In this preliminary study, vest CPR, despite its late application, successfully increased aortic pressure and coronary perfusion pressure, and there was an insignificant trend toward a greater likelihood of the return of spontaneous circulation with vest CPR than with continued manual CPR. The effect of vest CPR on survival, however, is currently unknown and will require further study. PMID- 8350884 TI - A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. AB - BACKGROUND: Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections. METHODS: We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up. RESULTS: The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment. CONCLUSIONS: The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora. PMID- 8350886 TI - Effect of dietary fish oil on renal function and rejection in cyclosporine treated recipients of renal transplants. AB - BACKGROUND: Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in cyclosporine-treated recipients of renal transplants. METHODS: In a randomized, double-blind trial, 33 recipients of first cadaveric kidney transplants who were treated with cyclosporine and prednisolone ingested 6 g of fish oil daily during the first postoperative year (the fish-oil group), whereas another 33 renal-graft recipients treated with cyclosporine and prednisolone ingested 6 g of coconut oil daily for three months after which time it was stopped (the control group). RESULTS: One year after transplantation, the fish-oil group had higher median values than the controls for glomerular filtration rate (53 vs. 40 ml per minute per 1.73 m2, P = 0.038) and effective renal plasma flow (214 vs. 178 ml per minute per 1.73 m2, P = 0.023) and lower mean arterial pressure (103 vs. 118 mm Hg, P = 0.0011). The cyclosporine doses in the two groups were similar. The cumulative number of rejection episodes was 20 in the controls, as compared with 8 in the fish-oil group (P = 0.029). One-year graft survival also tended to be better in the fish-oil group, (97 vs. 84 percent, P = 0.097). CONCLUSIONS: The daily administration of 6 g of fish oil during the first postoperative year has a beneficial effect on renal hemodynamics and blood pressure in renal-transplant recipients treated with cyclosporine. Although the fish-oil group had significantly fewer rejection episodes than the control group, graft survival at one year was not significantly better in the fish-oil group. PMID- 8350887 TI - Images in Clinical Medicine: Peutz-Jeghers syndrome. PMID- 8350888 TI - Nuclear cardiology (1). PMID- 8350889 TI - Treatment of multidrug-resistant tuberculosis. AB - The frequency of infections with M. tuberculosis resistant to antituberculous drugs is increasing in the United States and globally. This increase is a major threat to tuberculosis treatment and control programs. To prevent this situation from worsening, initial treatment programs that entail directly observed therapy supported by effective inducements or enforcements must be used. Retreatment of patients who have multidrug-resistant tuberculosis should be carried out in programs with comprehensive microbiologic, pharmacokinetic, psychosocial, and nutritional support systems. Regimens of multiple drugs, which generally are poorly tolerated and more toxic than traditional regimens, must be administered for 18 to 36 months. Resectional surgery may be required for substantial numbers of patients. For patients with AIDS who acquire tuberculosis caused by multiply resistant strains, the disease may prove lethal before effective therapy can be implemented. Ultraviolet irradiation systems should be used to protect health care personnel and other patients in high-risk environments. Enhanced federal, state, and local programs for prevention and control are urgently needed, and research to identify new medications and systems for their delivery is essential. PMID- 8350890 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 36-1993. A 28-year-old man with AIDS, persistent pancytopenia, and lymphoma. PMID- 8350891 TI - Resistance to urinary tract infection. PMID- 8350892 TI - A declaration of independence for health system reform. PMID- 8350893 TI - Reforming our health care system. PMID- 8350894 TI - Reforming our health care system. PMID- 8350895 TI - Reforming our health care system. PMID- 8350896 TI - Reforming our health care system. PMID- 8350897 TI - Reforming our health care system. PMID- 8350898 TI - Reforming our health care system. PMID- 8350899 TI - Reforming our health care system. PMID- 8350900 TI - Physician-payment reform. PMID- 8350901 TI - Physician-payment reform. PMID- 8350902 TI - Physician-payment reform. PMID- 8350904 TI - Physician-payment reform. PMID- 8350903 TI - Physician-payment reform. PMID- 8350905 TI - Vaccine-associated paralytic poliomyelitis. PMID- 8350906 TI - Reinfection with multidrug-resistant tuberculosis. PMID- 8350907 TI - Reinfection with multidrug-resistant tuberculosis. PMID- 8350908 TI - Death in a patient with primary pulmonary hypertension after 20 mg of nifedipine. PMID- 8350909 TI - Case 8-1993: cysticercosis. PMID- 8350910 TI - Varmus reassuring for NIH. PMID- 8350911 TI - Fidia fall-out. PMID- 8350912 TI - Prospects for growth hormone turn sour. PMID- 8350913 TI - US doctors campaign to support rbGH. PMID- 8350914 TI - Varmus nominated to head NIH. PMID- 8350916 TI - Neurotransmission and secretion. PMID- 8350915 TI - Cortical space race. PMID- 8350917 TI - Neurotransmission and secretion. PMID- 8350918 TI - Function of vertebrate T gene. PMID- 8350919 TI - ALS, SOD and peroxynitrite. PMID- 8350920 TI - A possible neuronal basis for representation of acoustic scenes in auditory cortex of the big brown bat. AB - Behavioural studies and field observations demonstrate that echolocating bats simultaneously perceive range, direction and shape of multiple objects in the environment as acoustic images derived from echoes. Cortical echo delay-tuned neurons contribute to the perception of object range, because focal inactivation of these neurons disrupts behavioural discrimination of range. We report here that response properties of delay-tuned neurons in the cortical tonotopic area of the bat, Eptesicus, transform the sequential arrival times of echoes with different delays into a concurrent, accumulating neural representation of multiple objects at different ranges. The sharpness of delay tuning systematically increases at each best delay in a subpopulation of these neurons while responses to echoes at different delays are accumulated. The resulting concurrent, multiresolution representation of echo delay corresponds to neural implementation of a common representation of images used in computational vision and may provide the basis for representing acoustic images of multiple objects as acoustic 'scenes'. PMID- 8350921 TI - Control of cell fate in C. elegans by a GLP-1 peptide consisting primarily of ankyrin repeats. AB - The homologous proteins GLP-1 and LIN-12 are required for cell interactions during nematode development. glp-1 and lin-12 are members of a gene family that includes Drosophila Notch and several vertebrate homologues. The members of this family have a single transmembrane domain and a similar arrangement of repeated amino-acid motifs (see Fig. 1). The mechanism by which proteins in this family function is not understood. One hypothesis is that these proteins are receptors, each with an extracellular domain that binds a ligand and an intracellular domain that influences the activity of downstream cell fate regulators. Here we report that a region of the GLP-1 intracellular domain, consisting primarily of six ankyrin repeats, is sufficient to direct cell fate. The cell fate transformations seen are similar to transformations caused by gain-of-function mutations in either glp-1 or lin-12 and do not rely on endogenous lin-12 or glp-1 activity. We propose that the ankyrin repeat region of GLP-1 is responsible for controlling downstream regulators of cell fate. PMID- 8350922 TI - Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria. AB - Ruffles are specialized plasma membrane ultrastructures of mammalian cells though to be integral to growth, development and locomotion. Induced by growth factors, mitogens or oncogene expression, ruffles are sites of filamentous actin rearrangement and are temporally associated with enhanced pinocytosis. But the function of ruffles, their mechanism of induction and their role in pinocytosis are not understood. We have observed formation of structures resembling ruffles associated with the site of entry of invasive Salmonella typhimurium. Here we report that ruffles elicited by invasive Salmonella directly mediate internalization of non-invasive bacteria in a macropinocytotic fashion, a phenomenon we term 'passive entry'. Furthermore, ruffles induced in the absence of Salmonella also facilitate passive entry. We present evidence that ruffles, common to many signalling events, comprise the macropinocytotic machinery mediating pinocytosis and are subverted by Salmonella so as to enter mammalian cells. PMID- 8350923 TI - Positive selection of T lymphocytes on fibroblasts. AB - Thymocytes are selected for expression of alpha beta T-cell antigen receptors (TCR) which recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. In the thymus the restriction element is imprinted on radioresistant stromal elements and on cells of haematopoietic origin. In mice negative for beta 2-microglobulin that are devoid of mature cytotoxic T lymphocytes, we find that intrathymic injection of different fibroblasts causes the maturation of CD4-CD8+TCRhigh thymocytes with distinct patterns of TCR V beta distribution. Here we show that in TCR-transgenic mice, intrathymic injection of L cells expressing the selecting H-2Kb molecule (L-Kb cells) reconstitutes the maturation of thymocytes bearing the transgenic TCR, and that in normal B10.BR (H 2k) mice, H-2Kb molecules expressed on L-Kb cells lead to the development of T lymphocytes with recognition restricted to H-2Kb. A class I MHC restriction element can thus be selected by interaction with fibroblasts, that is, cells of other than epithelial or haematopoietic origin. PMID- 8350924 TI - A retinoblastoma-binding protein related to a negative regulator of Ras in yeast. AB - The growth suppression function of the retinoblastoma protein (Rb) is though to be mediated by Rb binding to cellular proteins. p48 is one of the major proteins that binds to a putative functional domain at the carboxy terminus of the Rb protein. Here we report the isolation of a full-length complementary DNA (RbAp48) encoding p48. Complex formation between p48 and Rb occurs in vitro and in vivo, and apparently involves direct interaction between the proteins. Like Rb, p48 is a ubiquitously expressed nuclear protein. RbAp48 share sequence homology with MSI1, a negative regulator of the Ras-cyclic AMP pathway in the yeast Saccharomyces cerevisiae. Furthermore, like MSI1, human RbAp48 suppresses the heat-shock sensitivity of the yeast ira1 strains and RAS2Val19 strains. Interaction with p48 may be one of the mechanisms for suppression of growth mediated by Rb. PMID- 8350925 TI - Readers respond to "Mammoscam revisited". PMID- 8350927 TI - Sensitivity vs. specificity. PMID- 8350926 TI - Readers respond to "Mammoscam revisited". PMID- 8350929 TI - Abstracting journal articles. A personal experience. PMID- 8350928 TI - Cat germs! Pleuropulmonary pasteurella infection in an old man. PMID- 8350930 TI - Child abuse. PMID- 8350931 TI - Screening for cervical cancer. Pap smears can save lives. PMID- 8350932 TI - Durham, City of Medicine, USA. Part 3: The City of Medicine Awards Program and the future. PMID- 8350933 TI - Doctors, lawyers, and personal injury. Separating myth from fact. PMID- 8350934 TI - [Spontaneous lumbar epidural abscess]. PMID- 8350935 TI - [Increasing psychological morbidity]. PMID- 8350936 TI - [Paraneoplastic neurological syndromes, current diagnostic possibilities using antibody measurements]. PMID- 8350937 TI - [Taking blood along on travels, sense or nonsense?]. PMID- 8350938 TI - [Percutaneous endoscopic gastrostomy]. PMID- 8350939 TI - [Compared to whole body scanning thyroglobulin assay is reliable in the follow-up of thyroidectomized patients with thyroid carcinoma]. AB - OBJECTIVE: To determine whether it is reliable to do thyroglobulin measurements during thyroid hormone substitution (Tg ON) alone or whether it is also necessary to do 131I total body scanning (TBS) and Tg measurements after withdrawal of thyroid hormone substitution (Tg OFF) in the follow-up of patients with differentiated thyroid carcinoma. DESIGN: Retrospective. SETTING: University Hospital Nijmegen. METHODS: 202 Patients (151 females and 51 males, mean age 50.6 years) with differentiated thyroid carcinoma were examined in the period 1970-90. All patients had undergone total thyroidectomy and if necessary 131I ablation. 27 Patients with Tg antibodies were excluded (13.4%). In 175 patients Tg OFF levels were compared with TBS and clinical and radiological data. In 81 of them Tg ON levels were also compared. RESULTS: Specificity of Tg OFF and Tg ON measurement was 83 and 88%. Sensitivity of Tg OFF and Tg ON measurement was 100 and 92%. In detecting local residual thyroid tissue Tg OFF was superior to Tg ON. In detecting metastases Tg OFF and Tg ON were both superior to TBS. CONCLUSION: In the follow-up of patients with differentiated thyroid carcinoma it is reliable to do Tg measurements during thyroid hormone suppression. When Tg ON is detectable (> 3 pmol/l) TBS and Tg OFF measurement and if necessary further investigations have to be performed. PMID- 8350940 TI - [Microalbuminuria as risk factor for nephropathy in children with insulin dependent diabetes mellitus]. AB - OBJECTIVE: To assess the prevalence of microalbuminuria (> or = 30 mg/24 h) in children with insulin dependent diabetes mellitus (IDDM). DESIGN: Retrospective. SETTING: Department of Pediatrics, University Hospital, Free University of Amsterdam. METHODS: Albumin excretion rate was assessed in 24-hour voiding volumes in 71 children, mean age 11.8 yrs (range 3.5-17.9; 27 boys and 43 girls). Mean duration of IDDM was 5.4 yrs (1.0-5.0). Patients with albuminuria were compared with patients without microalbuminuria. Results of angiotensin converting enzyme inhibition (n = 4) are presented. RESULTS: The prevalence of microalbuminuria was 16% (n = 11). In 7% (n = 5) the microalbuminuria was persistent; in 9% (n = 6) it was intermittent. The mean age of the children with microalbuminuria (14.0 years; 8.9-17.4) was significantly higher than the age of the children without this disorder (11.7 years; 3.5-17.9). Two prepubertal children had developed microalbuminuria. The group with microalbuminuria had a significantly higher age at onset of the disease (8.1 years; 1.9-13.0) than the group without microalbuminuria (5.8 jaar; 0.9-14.5). The daily dose of insulin in the group with microalbuminuria was significantly higher (1.15 U/kg; 0.6-1.56) than in the group without microalbuminuria (0.97 U/kg; 0.20-1.87). There was no correlation between microalbuminuria and the duration of the disease. CONCLUSION: Microalbuminuria may exist as early as the prepuberal period, but is found more frequently in children with IDDM who have entered puberty. There is a correlation between microalbuminuria and the age which it develops, the age at onset of the IDDM and the daily dose of insulin. Secondary prevention of diabetic nephropathy with ACE inhibition appears to be possible. PMID- 8350941 TI - [Necrotizing fasciitis caused by Group-A beta-hemolytic streptococci]. PMID- 8350942 TI - [Results of allogeneic bone transplantation in spondylodesis of the spine]. PMID- 8350943 TI - Characterization of lymphokine-activated killer cells from peripheral blood and lymph nodes of non-Hodgkin's lymphoma patients. AB - Peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) from non Hodgkin's lymphoma patients were tested for LAK cell cytotoxicity using appropriate targets in a short-term 51chromium-release assay. The results showed a significant depression in LNL-LAK activity suggesting the reduced capacity of LNL to generate LAK cells. LNL-LAK cells demonstrated significantly low percentages of cells expressing CD16, CD56 and CD25 as compared to PBL-LAK of patients and healthy donors. The reduced capacity to generate LAK cells in lymph nodes could be due to the presence of low numbers of NK cells which are thought to be the main precursors of LAK cells. The IL-2 producing ability of lymph node mononuclear cells was found to be significantly higher than that of peripheral blood mononuclear cells from both healthy donors and NHL patients. PMID- 8350945 TI - Interleukin-2 production by human leukemia cell lines of pre-B cell origin. AB - Cells of 7 tested human leukemia cell lines of pre-B cell origin (as characterized by immunophenotyping and by the expression of cytoplasmic mu chains, but not by surface immunoglobulins) produced after stimulation with bacterial lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) a lymphokine activity which supported the growth of the interleukin-2 (IL-2) dependent CTLL-2 cell line. Three pieces of evidence indicate that the secreted lymphokine was functionally and antigenically very similar, if not identical, to human IL-2: (1) The lymphokine supported the growth of murine IL-2-dependent CTLL 2 cells, which did not respond to human lymphokines other than IL-2, but it did not stimulate the growth of murine IL-3-dependent FDC-P2 cells, (2) the biological activity of the lymphokine was inhibited by monoclonal antibody (mAb) anti-human-IL-2, and (3) the proliferation of IL-2-dependent cells in the presence of the active material was completely inhibited by the inclusion of the anti-mouse-IL-2 receptor (IL-2R) mAb. Since leukemia cells of immature B-cell origin also synthesize IL-2R, the human pre-B cell leukemias could represent another type of hematological malignancy where the autocrine processes of IL-2 production and utilization are involved in the expansion of the disease. PMID- 8350944 TI - Protective role of vanadium in the survival of hosts during the growth of a transplantable murine lymphoma and its profound effects on the rates and patterns of biotransformation. AB - Vanadium, as ammonium mononium monovanadate, has been found to have anticarcinogenic effect in host mice bearing a transplantable ascitic lymphoma. The potentiating effect of vanadium was supported by biochemical analysis of autopsies relating to markers like microsomal cytochrome P-450, UDP glucuronyl transferase (UDPGT) and cytosolic glutathione-S-transferase (GSHT) in the hepatic tissue of the hosts, which showed substantial alterations in the extent of tumor regression as compared to their lymphoma and normal counterparts, prolonging the survival of the hosts. PMID- 8350946 TI - Characterization of ferritin from spleens of patients with Hodgkin's disease (HD). AB - Ferritin, an iron-storing protein, was isolated from disease-involved and uninvolved regions of spleen biopsies obtained from patients with Hodgkin's disease (HD). Ferritin from all human spleen biopsies showed a major band of polypeptide of M(r) around 20 kDa in 1D-SDS-PAGE analysis. The corresponding bands for horse spleen ferritin and apoferritin (Sigma) were at a slightly lower M(r) level. In isoelectrofocusing (IEF) studies, the pI values of human spleen ferritin from the uninvolved and involved regions were 4.55 and 4.14, respectively. These were more acidic than that of horse spleen ferritin (4.79). Human spleen ferritin from the involved region also differed from that of the uninvolved region in the pattern of CNBr-generated peptide maps in 1D-SDS-PAGE. These results suggest that the presence of Hodgkin's disease in human spleen is associated with some physiochemical changes in the tissue ferritin. PMID- 8350948 TI - Importance of tumor size and repopulation for radiocurability of skin cancer. AB - Data on 946 skin cancers treated by radiation were used to estimate the importance of repopulation. Six different treatment regimes were used from a single dose to 74 Gy given in 47 fractions. High local control of the small skin cancers (L 1 cm) was independent of dose fractionation. For large tumors, only 74 Gy in 47 fractions was the optimal treatment. Time factor analysis showed a steep increase in the NTD50 values between day 28 and 65 of treatment. This implies that tumor clonogen repopulation starts around 4 weeks of treatment. The present results showed a three-component dose response curve instead of the two-component curves which were found for head and neck and bladder cancer. PMID- 8350947 TI - Teratogenicity of cyclophosphamide in New Zealand white rabbits. AB - Pregnant rabbit does received daily oral doses of 6.2 or 18.6 mg/kg cyclophosphamide (CP) on days 6-20 of gestation. On day 29, shortly before term, the uterine content was removed by Caesarean section. At the dose of 6.2 mg/kg CP maternal mortality was 2/9 does and at 18.6 mg/kg CP one abortion was recorded. Body weight gain of pregnant females was essentially unaffected by CP treatment. Both doses of CP elicited significant dose-dependent decrease of fetal body, organ (heart, lung, liver, kidney) as well as placental weight. After treatment with 18.6 mg/kg CP, gross examination of fetuses revealed significantly increased incidence of exophthalmos, cleft palate/lip, syndactyly, and brachycardia. Skeletal anomalies and malformations, significantly increased after the higher CP dose, included sternebrae, back-bone and limb defects. Oral administration of CP to rabbits in the dose of 18.6 mg/kg during organogenesis resulted in pronounced embryotoxic and teratogenic changes. PMID- 8350949 TI - Estradiol receptor and prognosis in human breast cancer and its metastases. AB - Follow-up of 86 patients for at least 40 months confirmed age dependency of receptor binding capacity in primary breast tumors but not in lymph node metastases. In most cases receptor binding capacity was higher in lymph node metastases than in primary tumors. Prognosis of the disease expressed as percentage of patients who survived and had a disease-free interval is related to receptor binding capacity of the primary tumors investigated. In our investigation, a value of 60 fmol/mg protein seems to be a suitable cut-off value to distinguish between breast cancer patients with good and bad prognosis. Receptor levels of lymph node metastases showed a similar behaviour as those of primary tumors related to percentage of patients who survived, but not to disease free interval. PMID- 8350950 TI - IgD paraproteinemias. AB - In a series of 2038 paraproteinemic sera, 9 IgD paraproteins (0.44%) were found. Clinical diagnosis of all the 9 was multiple myeloma. One patient had an IgD lambda plasmacytoma which developed into plasmocellular leukemia. Our series of IgD paraproteins consisted of 6 females and 3 males with a mean age of 58.5 years. The mean concentrations of IgD paraproteins were 6.7 +/- 4.26 g/l and the mean proteinuria was 5.1 +/- 4.76 g/24 h. Eight IgD paraproteins had light chains lambda and one had light chains kappa. PMID- 8350951 TI - Geographic variation of secular trends of breast cancer mortality in Spain. AB - Breast cancer mortality information contained in the available statistics derived from the Spanish death certificates has been reviewed. Mortality from breast neoplasms was grouped into three five-year periods: 1903-1907, 1931-1935 and 1975 1979. Age-adjusted rates were estimated for every province (n = 49) in each period, and confidence intervals for the standardized mortality ratios and adjusted rates were calculated. Results are presented with maps of Spain that illustrate provincial contrasts in each period. Secular breast cancer mortality trends in the provinces are discussed in comparison with those of other countries. Furthermore, values are compared with the geographical distribution of risk factors, the aim being to formulate hypothesis explaining the observed contrasts and suggesting some future research lines. PMID- 8350952 TI - Modulation of leukosialin (sialophorin, CD43 antigen) on the cell surface of human hematopoietic cell lines induced by cytokins, retinoic acid and 1,25(OH)2 vitamin D3. AB - Cell surface expression of leukosialin (sialophorin, CD43 antigen) on human neoplastic hematopoietic cell lines K-562, U-937, HL-60 and REH was determined with the aid of a new CD43 monoclonal antibody (Bra7G) by the immunochemical (radioimmunoprecipitation, immunoblotting) and immunocytofluorometric techniques. Interferon-gamma and TNF-alpha were utilized as the "physiological" inducers of differentiation-associated markers. The "non-physiological" inducer phorbol ester PMA induced down-regulation of leukosialin cell surface expression on immature erythroid-myeloid leukemia cell line K-562, but up-regulation of CD43 antigen on the promyelocyte leukemia cell line HL-60 and, to a lesser extent on the monocyte like U-937 and CALLA+ ALL cell line REH. Retinoic acid down-regulated leukosialin on both U-937 monocyte-like cells and the CALLA+ ALL cell line REH. In contrast to these data, interferon-gamma, TNF-alpha, retinoic acid and 1,25(OH)2-vitamin D3 induced the up-regulation of leukosialin in a promyelocytic leukemia cell line HL-60. PMID- 8350953 TI - Ceftriaxone versus ceftazidime plus aminoglycoside therapy for infections in patients with neutropenia after cytotoxic chemotherapy. Short communication. AB - One hundred and one patients undergoing anticancer chemotherapy due to hematologic malignancy were retrospectively divided into two groups: 67 patients were treated with ceftriaxone plus amikacin, receiving once daily (od) 2-4 g ceftriaxone, 1-1.5 g amikacin (those without a peripheral or central venous catheter) and 34 patients with central or peripheral venous catheter (CPVC) receiving ceftizidime 2 g three times daily (tid) plus amikacin 0.5 g tid i.v. Both groups were similar as to their isolated pathogens, localization of infection, and basic diagnoses of hematologic malignancies. There was no significant difference in efficacy between ceftriaxone plus amikacin versus ceftazidime plus amikacin, but the toxicity was lower in once daily ceftriaxone plus amikacin group. PMID- 8350954 TI - Erythrocyte glutathione peroxidase in patients with colon cancer. AB - Erythrocyte activity of glutathione peroxidase (GSH-Px) was measured in 26 patients with colon cancer and in 26 sex, age, height and weight matched controls. The patient group had a lower mean GSH-Px activity than the control group (p < 0.001). No correlation was found between glutathione peroxidase activity and sex, age, height, or weight, or between glutathione peroxidase activity and duration of the disease. The inverse correlation between the activity of this enzyme and the extent of the disease may be caused by a decreased absorption of selenium from the diseased colon. The significance of decreased GSH-Px in patients with this disease is unknown, but the possibility exists that this may further increase their risk of developing colonic cancer. PMID- 8350955 TI - Blood transfusion and survival after surgery for stage I and II breast cancer. AB - The records of 690 Stage I and II breast cancer patients (31% of them with transfusions), who underwent mastectomy with axillary dissection were examined whether perioperative blood transfusion might be detrimental to survival. The overall 5- and 10-year survival rates for 477 patients who had not received transfusions were 75% and 63% respectively, compared with 66% and 49% for those who had transfusions (p = 0.005). There was no significant difference between the groups in any other of the most important prognostic factors. An analysis of the subpopulation of patients with favorable prognostic factors yielded similar results. A multivariate analysis indicated that blood transfusion was one of the four variables significantly related to survival. PMID- 8350957 TI - Long-term results in hairy cell leukemia treated by splenectomy. AB - Splenectomy as a therapeutic modality has been evaluated in a group of 24 consecutive patients. Before and after splenectomy only supportive therapy was applied with the exception of two patients in whom corticosteroids were administered because of vasculitis. Radiation therapy was applied in one patient because of massive retroperitoneal lymphadenopathy. One patient received Leukeran shortly before the fatal outcome because his response to splenectomy was poor. Out of 24 patients 14 patients died. The median survival for the partial responders and non-responders was 6 months only. Patients with a complete response did not reach median survival yet and 8 of them (33% of the whole group) have been alive for more than 9 years, one patient for more than 20 years. Two distinct groups of patients with respect to the outcome of splenectomy can be distinguished: The first group is characterized by a rapid fatal outcome mostly within two years after splenectomy, the second group has a more favorable course with a plateau and only occasional deaths after the fourth year. PMID- 8350956 TI - Estrogen and progesterone receptor status in breast cancer in Kuwait female population. AB - The levels cytosol estrogen (ERc) and progesterone (PRc) receptors were determined in 315 primary breast cancers of female Arab patients aged 23-80 years. Most of breast cancers (78%) occurred in women aged 21-50 years, and only 22% were in women aged 51-80 years. Breast cancers containing ERc and PRc concentrations in the range 5-50 fmol/mg of cytosol protein (mg c.p.) were found with similar frequency in women aged under or over 50 years (53% for ERc and 43% for PRc, respectively). On the other hand, breast cancers with ERc values of > 50 and > 100 fmol/mg c.p. were twice as frequent in women aged over 50 years as in women aged under 50 years. The frequency of breast cancers with PRc level of over 50 fmol/mg c.p. in women aged over 50 years was only half that in those aged under 50 years. In breast cancers of Kuwait Arab women the higher values of ERc (> 100 fmol/mg c.p.) and PRc (> 50 fmol/mg c.p.) were less frequent than in other populations reported in literature. The low frequency of breast cancer in postmenopausal Kuwait women is associated with low proportions of tumors with higher ERc and PRc contents. In contrast to this, data from literature indicate that in the North Western European and American populations the postmenopausal incidence rise of breast cancers is associated with increased proportions of tumors with higher ERc and PRc levels. PMID- 8350958 TI - Regulatory role of T lymphocytes and NK cells in tumor allograft development. AB - In the present study, the respective roles of T cells and their subpopulations as well as of NK (natural killer) cells in antitumor immune responses were followed using the SaI (H-2a) allograft model. The development of this tumor in B10 (H-2b) mice was evaluated after pretreatment of the recipients with xenogeneic antithymocyte serum (ATS). Anti-Thy 1.2, anti-Lyt 2.2 and anti-L3T4 monoclonal antibodies were used in order to determine T lymphocyte phenotypes and to assess the frequency of TC/S and TH subpopulations at various periods of tumor development. Rabbit polyclonal anti-asialo GM1 antiserum was used for the identification of NK cells. In a previous work it was suggested that the first week following transplantation, the cells predominantly involved in the growth regulation of SaI belong to the TS subclass. Our results based on the use of anti Lyt 2.2 monoclonal antibodies have further supported this finding. The application of anti-Thy 1.2 on the 3rd and 5th day has hampered a secondary tumor growth while anti-Lyt 2.2 was effective when given on day 5. The depletion of Lyt. 2.2+ cells on day 3 resulted in the inhibition of both primary and secondary tumor development. On the other hand, when anti-Thy 1.2 was applied on day 7 after transplantation, the primary and secondary tumor growth was strikingly enhanced. It appears that Thy 1.2+ lymphocytes display at this period effector functions and contribute, in conjunction with macrophages, to subsequent tumor regression. The depletion of L3T4 cells on days 3 and 5 after tumor inoculation has resulted in primary tumor growth enhancement. This suggests that cells of the L3T4+ phenotype display at this time helper functions contributing to CTL proliferation and maturation. A further indication, supporting the possible suppressor effect of L3T4+ cells, counts from the finding that anti-L3T4 treatment results in an inhibition of secondary tumor growth. The anti-asialo GM1 treatment has not enhanced, at least significantly, primary tumor development but has partially or totally inhibited the growth of secondary tumors. It appears that cells of the GM1+ (NK cells) phenotype do not participate in any substantial way in the early phases of SaI tumor development in ATS treated allogeneic recipients. PMID- 8350959 TI - Stage dependence of NK cell activity and its modulation by interleukin 2 in patients with breast cancer. AB - NK cell activity was evaluated in breast cancer patients with different clinical stages of disease prior to surgery. In 58 patients with Stages I-III of breast cancer the peripheral blood NK cell activity was significantly reduced as compared to controls, and NK activity of 11 patients with Stage IV and metastases was significantly reduced as compared to both controls and patients with locoregional disease. In vitro treatment of peripheral blood lymphocytes (PBL) in medium with 10% fetal bovine serum (FBS) alone significantly increased NK cell activity in patients with Stages I-III and Stage IV of disease, although the level of NK cell activity of patients with Stage IV remained below that for less advanced disease. In vitro treatment of PBL of some Stages I-III patients (n = 41) with interleukin 2 (IL 2) gave a significant, dose-dependent enhancement of their NK cell activity so that it was significantly higher than basic NK activity of healthy controls. The results showed decrease of NK cell activity in breast cancer patients especially in advanced disease and enhancement with IL 2 indicating the possibility of immunotherapy in this neoplasm. PMID- 8350960 TI - Circulating immune complexes in Hodgkin's disease. Reactivity of IgG isolated from circulating immune complexes. AB - In our earlier report on circulating immune complexes (CIC) from sera of patients with Hodgkin's disease (HD), we demonstrated disease-associated increase in the intensity of a 40kD (pl 5.6) polypeptide in the CIC. In extension of these investigations, we now report that the 40kD moiety exists in CIC as a complex with IgG, and that IgG isolated from such CIC samples from sera of patients with HD shows preferential reactivity with the typical large binucleate Reed-Sternberg (R-S) cells in the sections of disease-involved lymph nodes from HD patients. PMID- 8350961 TI - Expression of p43 associated placental isoferritin (PLF) correlates inversely with cell growth in breast cancer cell lines MCF-7 and T47-D. AB - We have previously demonstrated that the expression of the recently described immunosuppressive antigen p43 in breast cancer patients correlates with early stages of the disease and a low degree of proliferation of the tumors. Attempts were made to evaluate the expression of p43 in two breast cancer cell lines (MCF 7 and T47-D) stimulated to proliferation by 17-beta estradiol and fetal bovine serum (FBS). p43 expression was determined by RIA technique using the new monoclonal antibody CM-H-9, the rate of proliferation was assessed by [3H]thymidine incorporation during 72 hours of incubation. Induction of proliferation by addition of 17-beta estradiol and FBS to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. The level of p43 expression in nonstimulated cells was low in comparison to that in cells cultivated routinely (15% FBS, no estrogen). However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen stimulated proliferation. Our in vitro results confirmed previous clinical observations describing an inverse correlation between p43 synthesis and degree of proliferation and differentiation in breast cancer for the first time. However, the pathologic mechanisms leading to this phenomenon need to be elucidated. PMID- 8350962 TI - In vitro cytotoxicity and mode of action of 1-alkylpyrrolidine N-oxides. AB - A new class of nonaromatic amine oxides was synthesized and tested for cytotoxic activity in vitro. The aim of this study was to find if there is any correlation between the cytotoxic activity of the investigated 1-alkylpyrrolidine N-oxides and their structure (as a structural parameter the number of carbon atoms m in the alkyl chain was used). Maximum activity was achieved with 1 tetradecylpyrrolidine N-oxide (C14) which was chosen for further biochemical studies. Further lengthening led to decrease in activity. The drug inhibited the incorporation rate of [14C] precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of Ehrlich ascites cells, the extent of inhibition being dependent on both time and concentration of the compound in the incubation medium. PMID- 8350963 TI - Effects of daunomycin and its macromolecular analog daunophilin on the proliferation of mammalian cells. AB - Effects of daunomycin and daunomycin bound to an HPMA copolymer (daunophilin) on the proliferation of mammalian cells cultivated in vitro were compared. One line of non-tumor cells (LEP human cells) and two tumor cell lines (human HeLa cells and C6 rat cells) were used. It was found that both daunomycin and daunophilin had an inhibitory effect on the proliferation of the three cell lines and that the effect was irreversible. Daunophilin had to be used in concentrations by two orders of magnitude higher (> 1 micrograms/ml) than daunomycin (> 0.01 micrograms/ml) to produce comparable effect on cell growth. PMID- 8350964 TI - Involvement of NOR-bearing chromosome in Rb-fusion: evidence from an in vivo murine sarcoma cell line. AB - The involvement of NOR-bearing chromosome in the formation of two stable and transmissible Robertsonian markers is reported in ascitic form of mouse Sarcoma 180 (S180) adapted in vivo to outbred strain of Swiss albino mice. The chromosomes involved in Robertsonian fusion included t(8;12) and t(16;17). PMID- 8350965 TI - Correlation of steroid receptors in synchronous tissues with survival in breast cancer patients. AB - Estrogen and progesterone receptors (ER and PR) were estimated in 129 synchronous (primary and metastatic lymph node) breast cancer tissues, of which 40% were premenopausal and 60% were postmenopausal. ER and PR accordance was seen in 68% and 70% patients, and ER and PR discordance was seen in 32% and 30%, respectively. The mean level of ER in patients having ER accordance was higher in responders than in nonresponders. In patients having steroid receptors in accordance, there was a trend towards gain of receptors (type II) in responders, and loss of receptors (type I) in nonresponders. In ER discordant cases 48% were of type I while in PR discordant cases 46% were of type I. In postmenopausal patients, survival was lower in patients showing accordance than in those showing discordance. In nonresponders showing loss of receptors in lymph node, the survival was shorter than in those who showed gain of receptors in lymph node. No such trend was seen in premenopausal patients. Our study suggests that in postmenopausal patients, survival was better related to ER accordance than ER discordance and PR accordance or discordance. However, a larger patient series is needed for confirmation. PMID- 8350966 TI - ROC analysis of benefit and limitation in radiotherapy for cancer of the oral cavity. AB - The ROC analysis of optimalization of radiation treatment of cancer of the oral cavity was carried out. Material of 210 patients with squamous cell carcinoma (SCC) of the oral cavity was included into the study. Based on dose-response curves for tumor and late mucosal reactions, iso-utility curves and optimal k values were estimated. Optimal k values decreased from 0.792 to 0.584 with extension of overall treatment time from 35 to 49 days. It may suggest that the planning of additional dose to compensate tumor clonogens repopulation during prolonged treatment time does not improve therapeutic gain in radiotherapy for cancer of the oral cavity. The ROC is a useful model to estimate optimal radiation treatment for a given tumor because it is independent of any arbitrary consensus or theoretical assumption. PMID- 8350967 TI - Effectiveness of moderate dose combination chemotherapy in Burkitt's lymphoma. AB - Twenty-five evaluable pediatric patients with histologically proven Burkitt's lymphoma were treated with moderate dose combination chemotherapy consisting of cyclophosphamide, vincristine, methotrexate and cytosine arabinoside (COMA regime) without central nervous system prophylaxis. Complete remission was achieved in 94.1% (16/17) of patients with Stage I, I R, II and III A disease, with disease-free survival of more than 3 years. This protocol was attended by minimal chemotherapeutic toxicity. This combination chemotherapy was ineffective in more advanced disease (Stages III B, IV), major cause of failure being progressive disease with central nervous system involvement. This study showed the effectiveness of moderate dose chemotherapy without CNS prophylaxis in early stage Burkitt's lymphoma including Stage III A and needs for aggressive chemotherapy with CNS prophylaxis in more advanced disease. PMID- 8350968 TI - Role of sputum cytology in the diagnosis of mediastinal germ cell tumor. AB - A rare case of germ cell tumor of the mediastinum infiltrating the lung and metastasizing to the supraclavicular lymph node in a 25-year-old male is presented. The patient presented with a history of superior vena cava syndrome and chest roentgenograms revealed an abnormal mediastinum. Primary positive diagnosis was made cytologically on sputum specimens. The peculiar cell type found in the Papanicolaou stained sputum smears were correlated with fine needle aspiration cytology of lung and lymph node, and confirmed the histologic pattern of the tumor metastasizing to the lymph node. To our knowledge, the present case is the first report of a primary mediastinal seminoma (germinoma) infiltrating the lung and diagnosed by sputum cytology. These results suggest the usefulness of sputum examination as an adjunctive diagnostic procedure in the detection of patients with possible lung infiltrated germinal neoplasms. PMID- 8350969 TI - Cigarette smoke exposure of school children: effect of passive smoking and vitamin E supplementation on blood antioxidant status. AB - Despite similar vitamin E concentrations, erythrocytes of 25 children of smoking parents had an increased tendency (p < 0.01) to peroxidize in vitro as compared with those of 28 children of nonsmoking parents. This difference was abolished by vitamin E supplementation (100 mg alpha-tocopherol acetate/day for 14 days). The increased susceptibility to erythrocyte peroxidation in the smokers may reflect lower erythrocyte glucose-6-phosphate dehydrogenase, glutathione peroxidase and superoxide dismutase activities (p < 0.001, p < 0.005, and p < 0.02, respectively) in children of smoking parents. Children of smoking parents seem to be under sustained oxidant stress with increased plasma-conjugated dienes (p < 0.01) and dehydroascorbate (p < 0.002) concentrations. Total plasma cholesterol was similar in children of smoking and nonsmoking parents, and was unaffected by vitamin E supplementation. Indices of sustained oxidant stress in children of smoking parents were partially ameliorated by vitamin E supplementation. PMID- 8350970 TI - [Photoablation using Excimer laser irradiation--a suitable concept for microneurosurgery?]. AB - The suitability of Excimer laser beam for microneurosurgery was investigated in an animal experimental study. Cranial bones, cortex and the nervus ischiadicus of the rat were irradiated with 193 nm argon fluoride, 248 nm krypton fluoride, 308 nm xenon chloride and 351 nm xenon fluoride. After survival times of up to 30 days microscopic and electron optic findings of laser lesions at the tissues mentioned above, were studied. By means of the Excimer laser beam high precision tissue effects without or with only low thermal damage to the surrounding tissue were produced with any desired depth of penetration or extension. In analogy with the experiences gathered from animal experiments, a possible use is discussed for the removal of bone tissue around cranial nerves or vascular structures, of epileptogenic foci, or for cutting off pathways in pain surgery (e.g. the zone of entry of the dorsal root of spinal nerves). PMID- 8350971 TI - [The prognostic value of AEP and SEP values in subarachnoid hemorrhage. An analysis of 64 patients]. AB - In 64 patients with confirmed subarachnoid haemorrhage the clinical grading according to Hunt and Hess was compared to the initial findings of BAEP und SEP to elicit possible prognostic statements. Clinical and electrodiagnostic findings showed a high correlation. Patients without or with only slight alterations of amplitude and/or latency generally showed a favourable course. Recurrent haemorrhages or internal complications which can be decisive for outcome cannot be predicted by clinical or electrodiagnostic findings. The alterations of BAEP and SEP increase parallel to severity of clinical findings. Bilateral loss of BAEP or SEP indicates poor prognosis. Prognostic statements can be made with certainty only in cases with primary poor clinical condition (Hunt-Hess Grade IV V) and marked alterations of evoked potentials. PMID- 8350973 TI - [Embolization of cerebral arteriovenous malformations--methods and clinical results]. AB - Interventional treatment by neuroradiological embolisation of cerebral arteriovenous angiomas has become an alternative to surgical exstirpation especially in problematic localisations and large-size malformations. Clinical results showing a marked reduction in attacks and recurrent haemorrhages, evident from a three-year report on 17 patients, confirm the value of the method even in case of only subtotal occlusion of the malformation. PMID- 8350972 TI - [Fiberoptic intubation of neurosurgical patients]. AB - Patients with cervical spine injury presenting with respiratory distress require airway management that does not compromise integrity of the atlanto-occipital joint. Endotracheal intubation by means of direct laryngoscopy is not suitable. The method of choice is nasotracheal intubation of the awake patient, using a flexible fibre bronchoscope. If anatomy or surgical access render the nasal approach impossible, fibre optic intubation can be performed orotracheally, utilising specific technical aids. Flexible fibrescopes are available in different sizes (length and diameter): selection is base on the patient's anatomical requirements. Aids to orotracheal intubation are constructed with a bore wide enough to accommodate an endotracheal tube, and a face mask equipped with an extra intubation port allowing introduction of an endotracheal tube, slipped over a fibrescope. Premedication of the patients consists of an orally administered benzodiazepine. Topical anaesthesia and vasoconstriction of the nasal passages are achieved by cocaine (5-10%), or a local anaesthetic, combined with a vasoconstrictor. The selected nostril is prepared by means of introducing a nasopharyngeal airway, which--lubricated with xylocaine gel and left in place for few minutes--widens the nostril and facilitates passage of the endotracheal tube. Through the other nostril, oxygen is administered. Systemic analgo-sedation is strictly limited to fentanyl, 0.1 mg i.v. Topical anaesthesia of the larynx and cranial trachea is achieved by xylocaine, 2%, administered under direct vision through the instrumentation channel of the fibrescope.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350974 TI - Three-dimensional videomonitor in microsurgery. AB - The operation microscope was equipped with two small camera heads on both sides, with a 35-mm still camera, and with or without a binocular observer tube. These camera heads were connected with a 3-dimensional (3D) converter. The operator can observe the 3D images of the operation field on a TV monitor through polarization glasses. The microscope with two camera heads is easy to handle because these camera heads are small and light. This is a promising monitoring system for microsurgery. PMID- 8350975 TI - [Solitary intracranial late metastasis of a granulosa cell tumor of the ovary. Case report and review of the literature]. AB - A 75-year old patient was admitted to hospital in June 1989. She was suffering from headache since three months. In the neurological examination a mild hemiparesis on the left side, personal changes and apractic disturbances could be found. 10 years before a granulosa-cell tumour of the left ovary was extirpated, postoperatively the patient received radiation and polychemotherapy. CT-scan and MRI of the head showed a tumour parieto-occipital on the right hemisphere with multiple cystic and solid areas. The tumour was extirpated in toto. The postoperative course was uneventful. Primary tumour of the left ovary and intracranial metastasis showed the same histological findings. PMID- 8350976 TI - Lumbar radiculopathy caused by a lost silverclip. AB - The case of an adult patient with lumbar radiculopathy (L:4) caused by a migrated silverclip, which was probably lost during the successful extirpation of a cerebellar tumor many years before is presented. The clip was removed surgically and the nerve root was submitted to a partial neurolysis. Increased tension in the root due to corrosion of the clip and scar formation is the proposed pathophysiological mechanism in this case. PMID- 8350977 TI - [An unusual case of a blow-out fracture. Entrance of a bone fragment into the frontal lobe after a ski accident]. AB - Due to a ski accident a 16-year old girl suffered from headache, periorbital hematoma and ptosis of the right eyelid. No penetrating injury could be seen, but in the CT scan a blow-out fracture of the orbital roof and floor was verified. Since there was no evident lesion of the eye muscles, an operative indication could only be a neurosurgical one. Because of the traumatic connection between frontal cerebrum and sinus maxillaris we expected a CSF rhinorrhoea, which could not be confirmed. PMID- 8350978 TI - Current bibliographies of neuropeptides prepared by The University of Sheffield Biomedical Information Service. PMID- 8350979 TI - Immunocytochemistry of sequence-related neuropeptides in Drosophila. AB - Based on structure, activity, and expression, the Drosophila drosulfakinin I peptide (DSK I; FDDY(OSO3H)GHMRFamide) is similar to the vertebrate peptide, cholecystokinin. Dromyosuppressin (DMS; TDVDHVFLRFamide) is an abundant peptide isolated from adult Drosophila which shares a high degree of sequence homology with peptides isolated from chicken, cockroach, fleshfly, and locust. DSK I and DMS, encoded by different precursors, have similar expression patterns in larval brain tissue; each localizes to cells in the anterior and medial protocerebrum. Because of the precedence for coexistence of neural messengers, it was of interest to determine the cellular expression patterns relative to one another. The question of whether the two peptides were expressed in the same cells was resolved using an immunofluorescent double-labeling technique developed for sequence-specific antisera raised in separate animals of the same species. Double labeling was done using a combination of indirect and direct immunofluorescence. DSK I and DMS were shown to localize to different cells in close proximity to one another in the larval brain. The non-overlapping expression patterns of these peptides illustrate the complete lack of cross-staining with this technique. PMID- 8350980 TI - Interleukin-1 beta measured by radioimmunoassay in the rat spleen and thymus is increased during chronic inflammatory stress. AB - We have developed an extraction method and radioimmunoassay for the measurement of interleukin-1 beta (IL-1 beta) in rat tissues, using an antibody specific for IL-1 beta, IL-1 beta was detected in the spleen and thymus of control rats. Adrenalectomy (ADX) had no effect upon control levels of IL-1 beta. In animals with adjuvant-induced arthritis, IL-1 beta content in the spleen and thymus increased after 14 days. These increases in tissue IL-1 beta contents were not evident in ADX arthritic animals. We conclude that IL-1 beta synthesis is stimulated in tissues of the immune system following the development of adjuvant induced arthritis. Failure to observe elevated levels of tissue IL-1 beta in ADX arthritic rats may be evidence for tissue depletion due to increased IL-1 beta release in the absence of circulating corticosteroids. PMID- 8350981 TI - Partial reconstruction of the adult Lurcher cerebellar circuitry by neural grafting. AB - Solid cerebellar grafts, taken from normal mouse embryos (gestational day 12-14), were transplanted into the cerebellum of adult Lurcher mice. The degree of Purkinje cell replacement was analysed one to three months after transplantation by means of immunocytochemistry (antibodies against calbindin, cGMP-dependent protein kinase and neurofilament proteins) and electron microscopy. Grafted Purkinje cells succeed in moving out of the graft and migrate into the host cerebellar cortex. They are present next to the graft in the granule cell and molecular layers, and far from the graft remnant, only in the molecular layer, indicating that, although both layers subserve Purkinje cell migration, the molecular layer is the ultimate target. In the host molecular layer, axons of transplanted Purkinje cells form thick bundles running in the frontal plane over long distances. Most of them terminate in the upper granule cell layer by enlarged bulbs resembling collapsed growth cones. Axons reaching their normal targets (the neurons of the deep cerebellar nuclei) are observed only in cases where the granule cell layer is disrupted and/or grafted Purkinje cells remain in the white matter. The projection is massive only from grafts lying in the close vicinity of the target neurons. Electron-microscopic analysis of grafted Purkinje cells populating the host cerebellar cortex reveals that their synaptic investment is abnormal. In the molecular layer, where the normal inputs are reduced, the compartmentation in proximal and distal dendritic segments is severely affected, climbing fibre synapses only form on a minority of grafted cells and "pinceau" formations are absent. In the granule cell layer, the synaptic investment is similar to that of Purkinje cells in agranular cerebellum, and even heterelogous synapses with mossy fibres have been observed. These results, compared to those previously obtained with grafting experiments in Purkinje cell degeneration mutant mouse, allow us to conclude that: (i) the Purkinje cell-deficient molecular layer of the host, despite its severe atrophy and reactive gliosis, still exerts a positive neurotropism specific for grafted Purkinje cells; (ii) the unlesioned host granule cell layer underlying the molecular layer containing grafted Purkinje cells, even if almost depleted of granule cells, remains an obstacle for the re-establishment of a corticonuclear projection; and (iii) the degree of synaptic integration of grafted Purkinje cells is directly related to the nearby presence of available host axon terminals. Hence, owing to the atrophy of the Lurcher cerebellum, the postgrafting restoration of the cerebellar cortical circuit is much less complete in this mutant. PMID- 8350982 TI - Hippocampal localization of 5'-nucleotidase as revealed by immunocytochemistry. AB - The distribution of binding sites for an antibody against ecto-5'-nucleotidase was investigated in the mouse hippocampus by light microscopical immunocytochemistry. The antibody selectively labels a band corresponding to the innervation area of mossy fibre terminals within area CA3. Area CA1 as well as the dendate gyrus are negative. In area CA3 only the proximal but not the distal parts of the apical dendrites of pyramidal cells are labelled. Labelling is in the form of large dots around dendrites of pyramidal cells suggesting that mossy fibre terminals are immunopositive. In contrast, an antibody against the ubiquitous synaptic vesicle protein SV2 labels the large mossy fibre terminals as well as fine and punctate structures in the dendritic and somatic regions throughout the hippocampus. Labelled astrocytes can be found in the entire hippocampus and are frequent in the stratum radiatum and stratum oriens of the CA1 region. Immunopositive astrocytic processes can be found in association with capillary walls. Our results suggest that ecto-5'-nucleotidase may play a crucial role in the hydrolysis of AMP to adenosine at the mossy fibre synapses. Thus, at these synapses, 5'-nucleotidases could function both in completing the extracellular hydrolysis of synaptically released ATP as well as in the extracellular formation of adenosine. PMID- 8350983 TI - Localization of dynamin: widespread distribution in mature neurons and association with membranous organelles. AB - Tissue distribution and intracellular localization of dynamin by immunoblotting and immunocytochemistry is investigated in this study. Dynamin was widely expressed in all the neurons we examined, and was especially abundant in the central nervous system after maturation, although its expression presented regional heterogeneity. Dynamin was present most abundantly in cerebellar Purkinje cells and hippocampal pyramidal cells, and to a lesser extent in motor neurons and peripheral nerves. However, dynamin was nearly absent in cells such as anterior pituitary cells and adrenal medullary cells which secrete mainly dense cored vesicles. Dynamin was localized not only in cell bodies, axons, and synapses but also in dendrites. Subcellular fractionation indicated that dynamin existed in the membrane fraction as well as in the soluble fraction. In ligated peripheral nerves, dynamin colocalized with tubulovesicular membranous organelles transported mainly anterogradely. By transfection of dynamin cDNA into mouse fibroblast L-cells, we showed it colocalized with some membranous organelles but not with microtubules. Our results show that dynamin is associated with membranous organelles in vivo, although a certain amount of dynamin also exists in the soluble fraction and is distributed diffusely throughout mature neurons. The data suggest that dynamin's fundamental role involves membrane trafficking in neurons in the central nervous system rather than in sliding microtubules as a motor protein. PMID- 8350984 TI - Ionic mechanisms underlying the depolarizing and hyperpolarizing afterpotentials of single spike in guinea-pig cingulate cortical neurons. AB - Intracellular recordings and hybrid single-microelectrode voltage-clamp techniques were used to study the ionic mechanisms underlying the afterdepolarization and the subsequent slow afterhyperpolarization that followed a single action potential in layers V/VI neurons of the guinea-pig anterior cingulate cortex in in vitro slices. Both the afterdepolarization and afterhyperpolarization were markedly suppressed in size by addition of Co2+ or Cd2+, reduction in extracellular Ca2+, and intracellular EGTA injection. On the other hand, elevation of extracellular Ca2+ concentration augmented the amplitudes of the afterpotentials. The afterdepolarization amplitude was selectively depressed by the stilbene derivatives, 4-acetamido-4' isothiocyanatostilbene-2,2'-disulphonate, disodium 3H2O, and 4,4' diisothiocyanatostilbene-2,2'-disulphonic acid, disodium salt. Reduction in external Cl- and intracellular Cl- injection enhanced the afterdepolarization amplitude without affecting the afterhyperpolarization. The null potentials for the afterdepolarizations recorded with K acetate- and Cs acetate-electrodes were 68 and -63 mV, respectively. The slope of the null potential obtained with K acetate electrodes or Cs acetate electrodes was 49 and 53 mV, respectively, per log unit of the external Cl- concentration. Reduction in external K+ markedly depressed the afterdepolarization and augmented the afterhyperpolarization in size, whereas rise in external K+ markedly augmented the afterdepolarization and depressed the afterhyperpolarization. The null potential for the afterhyperpolarization recorded with K acetate electrodes was -94 mV. The slope of the null potential was 57 mV per log unit of the external K+ concentration. Reduction in extracellular Na+ concentration slightly depressed both the amplitudes of the afterdepolarization and afterhyperpolarization. A hybrid voltage-clamp analysis revealed a slow decaying inward current and a subsequent outward current that followed an action potential. Both the amplitudes of the inward current corresponding to afterdepolarization and the outward current corresponding to afterhyperpolarization were suppressed by addition of Co2+. Reduction in extracellular Cl- concentration augmented the inward current amplitude without significantly affecting the outward current. These results indicate that the afterdepolarization is mainly due to an increase in a Ca(2+) activated Cl- conductance, while the afterhyperpolarization is mainly generated by an activation of Ca(2+)-mediated K+ conductance. PMID- 8350985 TI - Preferential expression of superoxide dismutase messenger RNA in melanized neurons in human mesencephalon. AB - The copper-zinc-dependent superoxide dismutase messenger RNA expression was studied at cellular level by in situ hybridization, using a 35S-labelled complementary DNA probe homologous to human copper-zinc-dependent superoxide dismutase messenger RNA, in the dopaminergic neuron-containing areas of the human mesencephalon (the substantia nigra pars compacta, ventral tegmental area, central gray substance and peri- and retrorubral region corresponding to catecholaminergic cell group A8). The autoradiographic labelling signal was localized in neurons. No detectable hybridization signal could be found in the glial cells. Copper-zinc-dependent superoxide dismutase messenger RNA was detected in melanin-containing neurons as well as in non-melanized neurons. Quantification at cellular level, taking the autoradiographic silver grain density as an index of the abundance of copper-zinc-dependent superoxide dismutase messenger RNA, indicated that hybridization level was higher in the melanized than in the non-melanized neurons within a region. Among melanized neurons, cellular copper-zinc-dependent superoxide dismutase messenger RNA content was lowest in the neurons of the substantia nigra. No significant difference in levels of transcripts was evidenced between the groups of non melanized neurons. The data suggest that the abundance of copper-zinc-dependent superoxide dismutase messenger RNA is higher in the mesencephalic neurons containing neuromelanin compared to other neurons. Thus, the melanized neurons have a particular defence system against oxygen toxicity, which may represent a basis for their preferential vulnerability to Parkinson's disease. PMID- 8350987 TI - Serotonergic innervation of the mature and developing lateral septum of the rat: a light and electron microscopic immunocytochemical analysis. AB - The serotonergic innervation of the adult and developing lateral septum of the rat was studied with immunocytochemical techniques at the light and electron microscopic levels. A few, relatively thick serotonergic fibres are found in the lateral septum at the time of birth, but they are restricted to its medial part. They subsequently extend towards the lateral ventricle, increase in number and attain their final distribution pattern by the end of the first postnatal week. Thereafter they become finer, with regularly spaced varicosities, show a higher density, and generally exhibit features, density, and pattern of innervation comparable to the adult at the end of the third postnatal week. In the dorsal portion of the lateral septum, serotonergic fibres form characteristic pericellular basket-like arrangements around cell somata and their primary dendrites. These baskets are first observed at P7, and subsequently increase both in number and in terms of the number of serotonergic terminals which they comprise. The present findings suggest that the development of serotonergic innervation of the lateral septum parallels the neuronal differentiation in this area. Ultrastructural analysis has shown that the vast majority (congruent to 95%) of serotonin varicosities make symmetrical synapses with somata, dendritic shafts and spines. These varicosities in new-born animals are in close association with neuronal elements, without any intervening neuroglial processes, but towards the end of the first postnatal week they exhibit well-defined synaptic specializations. The mean diameter of serotonergic varicosities making synapses does not change substantially with age. Serotonin-receptive neurons have several morphological features in common with the type I cells described in a previous Golgi study of the lateral septum [Alonso and Frotscher (1989) J. comp. Neurol. 286, 472-487]. Some speculations on the chemical identity of the serotonin-receptive cells have been put forward in the present study but double labelling studies will certainly shed more light on the organization of the serotonergic innervation of the lateral septum. PMID- 8350986 TI - Characterization of human brain kynurenine aminotransferases using [3H]kynurenine as a substrate. AB - The brain metabolite kynurenic acid is an established broad-spectrum antagonist at ionotropic excitatory amino acid receptors. In the human brain, two distinct enzymes are capable of synthesizing kynurenic acid from its bioprecursor L kynurenine. Using [3H]kynurenine as the substrate, the two kynurenine aminotransferases (kynurenine aminotransferase I and kynurenine aminotransferase II) are now characterized using partially purified enzyme preparations. When assayed at its pH optimum of 10.0, kynurenine aminotransferase I showed pronounced oxo acid specificity (pyruvate >> 2-oxoglutarate). This co-substrate selectivity was lost when assays were performed at pH 7.4. Kynurenine aminotransferase I activity was potently inhibited by 2 mM glutamine, tryptophan or phenylalanine, but not by 2 mM alpha-aminoadipate or glutamate. In contrast to kynurenine aminotransferase I, kynurenine aminotransferase II showed a shallow pH curve with an optimum of about 7.4, displayed virtually equal activity with all of the nine 2-oxo acids tested and was not susceptible to inhibition by any of 10 amino acids (2 mM) which are known to serve as substrates for enzymatic transamination. Kinetic analyses, performed at pH 7.4 (kynurenine aminotransferases I and II) and 10.0 (kynurenine aminotransferase I), and using various concentrations of kynurenine, pyruvate or 2-oxoglutarate, respectively, substantiated the differences between the two enzymes and further elucidated the pH dependence of kynurenine aminotransferase I activity [apparent Km values for kynurenine with 1 mM 2-oxoglutarate: 515 microM (pH 7.4) and 22 microM (pH 10.0)]. Taken together, these data suggest that under physiological conditions, human brain kynurenic acid may derive preferentially from kynurenine aminotransferase II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8350988 TI - Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia. AB - Changes in nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 messenger RNA expression in the rat hippocampus following 20 min of transient forebrain ischemia were evaluated using Northern blot analysis and in situ hybridization histochemistry. Twelve hours after the insult, the level of nerve growth factor messenger RNA increased markedly in the granular cell layer of the dentate gyrus and by day 2 returned to control levels. The level of brain derived neurotrophic factor messenger RNA showed a persistent and moderate increase. The highest expression of brain-derived neurotrophic factor messenger RNA was seen in the dentate granule cells on day 2 after the insult, and then the expression returned to the control levels. At 2 days post-ischemia, contents of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor were reduced in the CA1 region, which may represent delayed loss of vulnerable CA1 pyramidal neurons. In contrast to brain-derived neurotrophic factor and nerve growth factor messenger RNA expression, the level of neurotrophin-3 messenger RNA declined in the CA1, the CA2 and the dentate granular layer immediately after ischemic insult. In the CA1 region, the reduced expression persisted for at least seven days, but in the dentate gyrus, neurotrophin-3 messenger RNA expression returned to the control levels after two days of post-ischemic recovery. These results suggest that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 genes are differentially regulated and that each of their gene products may play different roles in the central nervous system under pathophysiological conditions. PMID- 8350989 TI - Autoradiographic localization of 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1C/2 binding sites in the rat spinal cord. AB - Autoradiographic techniques revealed that 5-hydroxytryptamine1A, 5 hydroxytryptamine1B and 5-hydroxytryptamine1C/2 binding sites are differentially distributed in the spinal cords of adult male rats. In the dorsal horn, 5 hydroxytryptamine1A sites were dense in all laminae; 5-hydroxytryptamine1B sites were more dense in laminae I, III and IV than in lamina II; while 5 hydroxytryptamine1C/2 sites were very sparse. The dorsal commissure gray matter also exhibited very dense 5-hydroxytryptamine1A and 5-hydroxytryptamine1B binding. In the intermediate and central gray matter, all three sites were moderately dense at autonomic levels, with exceptionally dense1C/2 binding restricted to the intermediolateral nucleus at rostral thoracic levels. In the ventral horn, 5-hydroxytryptamine1A and 5-hydroxytryptamine1B sites were very sparse (except for very dense 5-hydroxytryptamine1A sites located in the dorsolateral nucleus of the pudendal nerve), while 5-hydroxytryptamine1C/2 sites were relatively dense in motor nuclei. Surprisingly, 5-hydroxytryptamine1B sites were moderately dense in the dorsal column corticospinal tract. These studies will provide an anatomical perspective for interpretation of the complex role of 5-hydroxytryptamine in regulating spinal cord function. PMID- 8350990 TI - Peptide YY: a neuropeptide in the gut. Immunocytochemical and immunochemical evidence. AB - Peptide YY immunoreactivity was detected in neuronal elements in the upper digestive tract of the rat, cat, ferret and pig by immunocytochemistry and radioimmunoassay combined with high-performance liquid chromatography. The two peptide YY antisera used do not recognize the related peptides neuropeptide Y and pancreatic polypeptide. In the rat peptide YY-immunoreactive nerve fibres were virtually restricted to the stomach smooth muscle of the minor curvature where they were numerous. Peptide YY-immunoreactive nerve cell bodies occurred in small ganglia on the serosal surface of the minor curvature. In the cat and ferret peptide YY-immunoreactive nerve fibres occurred in the circular smooth muscle layer of both the minor and major curvatures of the stomach and also in the upper small intestine; such fibres were numerous also in myenteric ganglia in these regions. In the pig, they were few but had roughly the same distribution as in the cat and ferret, except that they were quite numerous in thick muscle bundles close to the oesophagogastric junction. The presence of peptide YY-immunoreactive nerve cell bodies within the myenteric ganglia along the upper digestive tract of cat, ferret and pig, and in serosal ganglia of the rat stomach, indicates that at least some of the peptide YY-immunoreactive fibres demonstrated originate in or close to the gut wall. Double-staining experiments revealed that virtually all peptide YY-containing neurons and nerve fibres were distinct from those storing neuropeptide Y. Peptide YY-immunoreactive endocrine cells were encountered not only in the lower intestines but also in the stomach of the four species studied. In the antrum such cells were numerous and constituted a subpopulation of the gastrin-containing cells. In the oxyntic mucosa they were few and contained somatostatin. Radioimmunoassay revealed peptide YY-like peptides in gastric mucosa and smooth muscle from the upper digestive tract of all four species examined. The results of high-performance liquid chromatography suggest that the peptide YY-like material in the upper digestive tract is distinct from neuropeptide Y and pancreatic polypeptide and identical with authentic peptide YY except in the antral mucosa where only a small proportion of the peptide YY immunoreactive material eluted like authentic peptide YY. PMID- 8350991 TI - The role of Muller cells in the formation of the blood-retinal barrier. AB - We have compared the ability of Muller cells and astrocytes to induce the formation of barrier properties in blood vessels. Muller cells cultured from the rabbit retina, and astrocytes and meningeal cells cultured from the rat cerebral cortex, were injected into the anterior chamber of the rat eye, where they formed aggregates on the iris. We have examined the barrier properties of the vessels in those aggregates and, for comparison, the barrier properties of vessels in the retina, ciliary processes and iris. Two tracers were perfused intravascularly to test barrier properties. The movement of Evans Blue was assessed by light microscopy, and the movement of horseradish peroxidase by light and electron microscopy. Our results indicate that Muller cells share the ability of astrocytes to induce the formation of barrier properties by vascular endothelial cells, and we suggest that Muller cells play a major role in the formation of barrier properties in retinal vessels. PMID- 8350992 TI - Parvalbumin immunoreactivity in the hippocampus of the gerbil after transient forebrain ischaemia: a qualitative and quantitative sequential study. AB - Parvalbumin immunoreactivity is examined in the hippocampus of the Mongolian gerbil (Meriones unguiculatus) in controls and in animals subjected to 20 min of forebrain ischaemia produced by bilateral clipping of the carotids. In comparison with other species, the hippocampus of the gerbil is characterized by strong immunoreactivity of the (presumably excitatory) perforant pathway, and weak immunoreactivity (low numbers of neurons and scarce dendritic arbors) in nonpyramidal nerve cells (inhibitory neurons) of the CA1 area. These properties may play some role in the development and maintenance of seizures in this susceptible species. Parvalbumin immunoreactivity is rapidly and ephemerally increased in the hippocampus 15 min after reperfusion. Later on, there is a transitory decrease of parvalbumin immunoreactivity which is followed by an increase 6 h later in the stratum granulare hilus and CA3 area, and not until the first and second days in the CA1 area. This increase significantly surpasses the number of immunoreactive neurons in control animals in CA1 and CA3 from 48 h after reperfusion onwards. The effect is similar using different anaesthetics and does not occur in sham-operated animals. In contrast with these findings, the number of parvalbumin-immunoreactive neurons in the somatosensory cortex is not affected in our model of forebrain ischaemia. On the other hand, GABA immunoreactive neurons in CA1 are preserved during the first week after reperfusion, although an increase in the number of these cells occurs at the end of this period. Delayed neuronal death occurs in the CA1 area 48 h after ischaemia, and marked reduction in the number of CA1 neurons is found by the end of the first week. Eighty per cent of the remaining cells in CA1 at day 7, and 83% at day 15, are parvalbumin-immunoreactive nonpyramidal neurons in contrast to 3% parvalbumin-immunoreactive cells in control animals. These findings indicate that GABAergic neurons in CA1 are preserved after forebrain ischaemia, and that parvalbumin in CA1 neurons is associated with survival. PMID- 8350993 TI - Entorhinal cortex lesion induces differential responses in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in the rat hippocampal formation. AB - The hippocampus can be induced by deafferentation to selectively reorganize its neuronal input. Entorhinal cortex lesion, which causes degeneration of the perforant pathway, evokes sprouting of septal afferents as well as glutamatergic commissural/associational fibers in the deafferentated zone of the molecular layer of the dentate gyrus. Although the process of reactive synaptogenesis that follows deafferentation has been extensively studied, at present little is known about its molecular basis and the mechanism of initiation. In this study, following unilateral lesion of the entorhinal cortex, the time-course of possible alterations of insulin-like growth factors I and II, and insulin binding sites were evaluated by in vitro quantitative receptor autoradiography. [125I]Insulin like growth factor I receptor binding sites did not exhibit any significant variation between the contralateral and ipsilateral hippocampal formation at any time periods following lesion except in the molecular layer of the dentate gyrus (P < 0.05) at day 8. However, when compared with the unlesioned animals, a differential time-dependent response of [125I]insulin-like growth factor I binding sites was noted in selective layers of the hippocampus. [125I]Insulin like growth factor II receptor binding sites showed a significant decrease (P < 0.05) in the ipsilateral granular cell layer of the dentate gyrus only at day 14 post lesion. Interestingly, compared to controls, a dramatic bilateral increase (P < 0.05) in [125I]insulin-like growth factor II binding was evident between days 1 and 8 in most layers of the hippocampal formation. A lesion-induced bilateral increase (P < 0.05) in [125I]insulin binding sites was evident in all layers of the hippocampus between two to eight days and at 30 days post lesion. In selective layers, however, a significant increase (P < 0.05) in [125I]insulin binding sites was also observed at days 1 and 14 after lesion. These results, which are compatible with the process of degeneration and/or sprouting of the terminal fibers, suggest possible involvement of insulin-like growth factors and insulin in the sequence of molecular events that occur to facilitate neuronal repair and to promote neuronal survival following entorhinal cortex lesion. PMID- 8350994 TI - Cholesterol synthesis and lipoprotein reuptake during synaptic remodelling in hippocampus in adult rats. AB - Apolipoprotein E is synthesized and secreted by astrocytes in the hippocampus following lesions of the entorhinal cortex. It was proposed that apolipoprotein E, by analogy to its role in cholesterol transport in circulation, could be involved in the salvage and reutilization of non-esterified cholesterol released during terminal breakdown. The salvaged cholesterol could then be transported to neurons by apolipoprotein E-complexes and taken up via the apolipoprotein E/apolipoprotein B (low-density lipoprotein) receptor. To test this hypothesis, we have examined low-density lipoprotein receptor binding in brain sections of rats undergoing hippocampal reinnervation. The number of neuronal cells labelled by fluorescent Dil-low-density lipoprotein as well as the density of [125I]low density lipoprotein binding sites in the dentate gyrus were found to increase in parallel with the extent of cholinergic reinnervation occurring in the deafferented hippocampus. In contrast, hippocampal cholesterol synthesis fell by more than 60% at eight days post-lesion, but eventually returned to control levels at 30 days post-lesion. The transient loss of cholesterol synthesis coincided with a peak in hippocampal apolipoprotein E expression. A concomitant accumulation of sudanophilic lipids (cholesterol esters and phospholipids) was detected in the outer molecular layer of the dentate gyrus and in the hilar region. The present findings suggest that non-esterified cholesterol released during terminal breakdown is esterified, transported via the apolipoprotein E transport system to neurons undergoing reinnervation, and take-up through the low density lipoprotein receptor pathway where it is presumably used as a precursor molecule for the synthesis of new synapses and terminals. PMID- 8350995 TI - Acetylcholinesterase activity and post-lesional plasticity in the hippocampus of young and aged rats. AB - Applying quantitative microscopic histochemistry, the activity of acetylcholinesterase was determined in the various layers of the rat hippocampus at three different levels along the rostrocaudal extent. Two age groups of animals were examined: young adults (two to three months old) and aged subjects (26 months old). Young adults were divided into controls, and animals killed eight and 35 days following bilateral ibotenate lesioning of the medial septum diagonal band complex. Aged rats were divided into controls and animals 35 days post-lesion. Analysis of variance revealed that the mean acetylcholinesterase activities of the entire hippocampus of individuals were not significantly different between young and aged rats when averaged across controls and 35 days post-lesion. There was a significant decrease of acetylcholinesterase activity ( 52%) in young adults eight days post-lesion as compared to controls, but a significant increase (+63%) took place until 35 days post-lesion as compared to eight days post-lesion. Significantly lower activities existed, however, in young (-22%) and aged rats (-18%) 35 days post-lesion as compared to controls. This decrease in mean activity was not age dependent. As acetylcholinesterase is considered to be a good cholinergic indicator in the hippocampus, the results suggest a homotypic collateral sprouting from spared cholinergic afferents following ibotenate lesion of the medial septum-diagonal band complex in young and aged rats. Based on the data obtained, it is reasonable to assume that there was no difference in the post-lesional plasticity of neuronal acetylcholinesterase between young adult and aged rats. PMID- 8350996 TI - The spectrum of levodopa-related fluctuations in Parkinson's disease. PMID- 8350997 TI - Accuracy of diagnosis of persistent vegetative state. AB - We reviewed pre-admission diagnosis in all patients referred for inpatient brain injury neurorehabilitation over a 5-year period (n = 193). All patients more than 1 month postinjury with diagnosis of coma or persistent vegetative state were selected for review (n = 49). We found that 18 (37%) of these patients were diagnosed inaccurately. Inaccurate diagnosis was more likely if the injury was more than 3 months before admission and the etiology of injury was trauma (48%). Results were statistically significant when traumatic injuries were compared with anoxic injuries (p < 0.10). Errors in diagnosis may result from confusion in terminology, lack of extended observation of patients, and lack of skill or training in the assessment of neurologically devastated patients. PMID- 8350999 TI - Status epilepticus: the interaction of epilepsy and acute brain disease. AB - We identified 217 patients with status epilepticus (SE), including all seizure types from all etiologies, over a 3-year period. There was a significant interaction between organic brain disease and a history of epilepsy in the development of SE. The majority of patients (59%) had no history of epilepsy. These patients were more likely to have acute precipitants associated with SE and less likely to have had prior brain disease. They were older, were more likely to have generalized convulsive seizures, and had a high proportionate mortality. Among the 88 patients with a history of epilepsy, a higher proportion had prior brain insults, but fewer had acute precipitants. These patients were younger and their mortality was low, but they often had recurrent SE before and after the identified episode. Significant acute or prior brain disease is an important factor in the development of SE, even in patients with a history of epilepsy. PMID- 8350998 TI - Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. AB - Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon 4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/- standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon 4 allele (0.40 +/- 0.026, p < or = 0.00001). These data support the involvement of ApoE epsilon 4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon 4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD. PMID- 8351000 TI - Progression after chronic manganese exposure. AB - We report a longitudinal follow-up study on six patients with chronic manganese induced parkinsonism following cessation of manganese exposure. Compared with the 1987 study, their parkinsonian symptoms showed a slow progression, particularly in gait disturbances such as freezing during turning and walking backward with retropulsion. The mean disability scores on the King's College Hospital Rating Scale were 15.0 +/- 4.2 in 1987 and 28.3 +/- 6.7 in 1991 (p = 0.003, paired t test). Review of the video records also confirmed a worsening of parkinsonism, especially in difficulty turning. Three of six patients receiving levodopa treatment had an initial improvement. The response decreased after 2 to 3 years. During the therapy, they did not develop on-off fluctuation or dyskinesia. We conclude that patients with manganese-induced parkinsonism may develop increasing neurologic dysfunction long after cessation of exposure and that their responses to levodopa are different from those of patients with Parkinson's disease. PMID- 8351001 TI - HIV-1-associated cognitive/motor complex: absence of neuronal loss in the cerebral neocortex. AB - We performed a postmortem morphometric study in six AIDS patients and six controls to determine if a neocortical neuronal loss occurs in HIV-1-associated cognitive/motor complex. Patients were selected during a prospective study including psychometric evaluation and neuroimaging, and none had focal lesions. Two had HIV-1-associated myelopathy with mild cognitive impairment, and four had HIV-1-associated dementia complex. Planimetry did not show any cerebral atrophy. Cortical thickness, mean neuronal size, and mean neuronal densities in Brodmann's areas 4, 9, and 40 were not statistically different in patients and controls. There were no significant changes in neuronal densities of columnar and laminar samples, indicating that there was neither global nor selective neuronal loss. HIV-1-associated cognitive/motor complex is not necessarily related to neocortical neuronal loss, but could be due to subcortical lesions or metabolic dysfunction. PMID- 8351002 TI - Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors. AB - We recently found that vibratory detection threshold is greatly influenced by the algorithm of testing. Here, we study the influence of stimulus characteristics and algorithm of testing and estimating threshold on cool (CDT), warm (WDT), and heat-pain (HPDT) detection thresholds. We show that continuously decreasing (for CDT) or increasing (for WDT) thermode temperature to the point at which cooling or warming is perceived and signaled by depressing a response key ("appearance" threshold) overestimates threshold with rapid rates of thermal change. The mean of the appearance and disappearance thresholds also does not perform well for insensitive sites and patients. Pyramidal (or flat-topped pyramidal) stimuli ranging in magnitude, in 25 steps, from near skin temperature to 9 degrees C for 10 seconds (for CDT), from near skin temperature to 45 degrees C for 10 seconds (for WDT), and from near skin temperature to 49 degrees C for 10 seconds (for HPDT) provide ideal stimuli for use in several algorithms of testing and estimating threshold. Near threshold, only the initial direction of thermal change from skin temperature is perceived, and not its return to baseline. Use of steps of stimulus intensity allows the subject or patient to take the needed time to decide whether the stimulus was felt or not (in 4, 2, and 1 stepping algorithms), or whether it occurred in stimulus interval 1 or 2 (in two alternative forced-choice testing). Thermal thresholds were generally significantly lower with a large (10 cm2) than with a small (2.7 cm2) thermode.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351004 TI - X-linked adrenoleukodystrophy: adult cerebral variant. AB - We report a unique case of a 43-year-old architect with adult-onset adrenoleukodystrophy who presented primarily with intellectual decline and no evidence of adrenal insufficiency. Serial MRIs taken over a number of months demonstrated the evolution of demyelination starting in the frontal white matter then shifting to the occipital white matter and finally resolving without any therapeutic intervention. Clinically, over this same period of time, the patient's symptoms resolved and he was able to return to work. The proband, his brother, and his nephew were found to have a color-vision defect. Each of these individuals had a red/green gene array that contained a 5' green-red 3' hybrid known to be associated with deutan color-vision defects. The proband's brother and nephew were otherwise normal. The gene that causes adrenoleukodystrophy appears not to be as close to the red/green color vision gene array on the X chromosome as previously reported. PMID- 8351003 TI - A 4, 2, and 1 stepping algorithm for quick and accurate estimation of cutaneous sensation threshold. AB - In quantitative sensory testing, certain methods may lead to incorrect estimates of vibratory (VDT), cool (CDT), or warm (WDT) detection thresholds. We have shown that the specific forced-choice algorithm of testing employed in our Computer Assisted Sensory Examination (CASE IV) system, when compared with other tests of nerve dysfunction, provides accurate and reproducible estimates of these thresholds. Because this forced-choice algorithm is time consuming and performance might be made worse by drowsiness or boredom, we explored other algorithms that might provide estimates of threshold similar to those obtained with the forced-choice algorithm, but more quickly. In a trial of 25 healthy subjects and 25 patients with neuropathy, the 4, 2, and 1 stepping algorithm with null stimuli, based in part on comparative data from computer simulation and insights from patient decision making, provides an accurate estimate of threshold. On average, the time needed for forced-choice testing was 12.8 +/- 2.9 minutes (mean +/- SD). For 4, 2, and 1 stepping testing, it was 2.7 +/- 2.5 minutes--a large saving of time. Since null stimuli were employed in the 4, 2, and 1 stepping algorithm, it was possible to monitor for spurious responses and repeat the test if they occurred at an excessive rate. The algorithm appears to be sufficiently robust to be recommended for clinical use and for some controlled clinical and epidemiologic trials. PMID- 8351005 TI - Third-nerve palsy due to penetrating trauma. AB - Penetrating trauma is an unusual etiology of third-nerve palsy. Of 815 hospitalized patients with third-nerve palsies, 20 had such an etiology, with gunshot wounds being the usual cause. PMID- 8351006 TI - The etiology of posterior circulation infarcts: a prospective study using magnetic resonance imaging and magnetic resonance angiography. AB - In a prospective study of 70 patients with infarcts in the posterior circulation admitted consecutively to a population-based primary-care center, we assessed infarct location and etiology using magnetic resonance imaging, three-dimensional time-of-flight magnetic resonance angiography, and noninvasive cardiac tests. The brainstem (mainly the paramedian pons) was the most commonly infarcted site (41/70, 59%), followed by the cerebellum (33/70, 47%). Combined supra- and infratentorial multiple vertebrobasilar infarcts occurred in 11 patients (16%). Overall, 27 patients (39%) had > or = 50% stenosis or occlusion of the basilar artery. There were other large-artery lesions in 19 patients (27%), including vertebral (V2-V4) stenosis or occlusion (in seven) and dolichoectatic vertebral/basilar arteries (in 12). Fifteen of the 70 patients had a potential cardiac source of embolism, which coexisted with large-artery disease in more than one-third of the cases. Cerebellar infarct without concomitant brainstem or occipital infarct was associated with cardioembolism (67%), while isolated paramedian pontine or midbrain infarct was associated with basilar artery stenosis (71%), suggesting in situ occlusion of the mouth of the perforators off the stenosed basilar artery. After exclusion of other potential causes of stroke, presumed small-artery disease associated with chronic hypertension remained the likely etiology in only 11 patients (16%), but these infarcts were not associated with any of the classical lacunar syndromes. Our findings emphasize the high frequency of severe intracranial large-artery disease in posterior circulation infarcts. PMID- 8351007 TI - Vascular distribution of paradoxical emboli by transcranial Doppler. AB - BACKGROUND AND PURPOSE: Paradoxical embolism through a patent foramen ovale is a contributory mechanism to stroke and may be diagnosed by contrast echocardiography. The intracranial distribution of these emboli has not been previously reported. METHODS: We used transcranial Doppler combined with agitated saline contrast injection to determine whether there was a preferential distribution of the contrast into the anterior or posterior intracranial circulation of patients with an acute stroke or transient ischemic attack. RESULTS: Forty-nine patients were studied--27 men and 22 women, with a mean age of 62.7 +/- 13.3 years (range, 29 to 85 years). Microcavitations were detected in the proximal right middle cerebral artery in 12 of 49 patients (24%). A patent foramen ovale was confirmed in all cases by simultaneous transesophageal echocardiography. Of the 12 patients, microcavitations were also detected in the proximal basilar artery in nine (75%). CONCLUSIONS: While paradoxical embolism appears to occur more frequently in the anterior circulation, the high rate of detection of microcavitations in the basilar artery suggests that paradoxical embolism to the posterior intracranial circulation may be more frequent than generally believed. PMID- 8351008 TI - Memory in patients with cerebellar degeneration. AB - Eleven patients with relatively selective cerebellar degeneration and 11 normal control subjects underwent a comprehensive neurologic and neuropsychological examination. The neuropsychological tests assessed general intellectual ability, different aspects of memory (effortful, automatic, and implicit memory processes), speed of information processing, and verbal fluency (using both category and letter fluency tasks). The results indicated that cerebellar patients were significantly impaired only on tasks requiring the use of executive functions, such as the initiation/perseveration subtest of the Mattis Dementia Rating Scale or the fluency tests, and on memory measures requiring greater processing effort. They performed normally on automatic and implicit measures of memory. Performance on the effortful memory and executive measures was not associated with neurologic variables or mood state. After controlling for the initiation/perseveration deficit, the effortful memory scores of the cerebellar patients were no longer different from those of controls. The present study suggests that memory in patients with relatively pure cerebellar dysfunction is only partially compromised and that the impairment is secondary to a deficit in executive functions. PMID- 8351009 TI - Suppression of dyskinesias in advanced Parkinson's disease. I. Continuous intravenous levodopa shifts dose response for production of dyskinesias but not for relief of parkinsonism in patients with advanced Parkinson's disease. AB - We characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's disease (PD) and fluctuating responses to oral levodopa/carbidopa. Dose response to ramped intravenous levodopa infusion was measured after overnight drug withdrawal on two occasions: first after chronic, intermittent oral levodopa/carbidopa, and second after 3 to 5 days of continuous intravenous levodopa. Continuous intravenous levodopa shifted the dyskinesia dose-response curve to the right, reduced maximum dyskinesia activity, but did not significantly alter dose response for relief of parkinsonism. Improvement in dyskinesia was apparent by the second day of continuous levodopa, during which ratios of plasma dopa/3-O-methyldopa remained constant. Our results support the hypothesis that relief of parkinsonism and production of dyskinesia by levodopa occur by separate mechanisms. PMID- 8351011 TI - Repeated exposure to the Mini-Mental State Examination and the Information-Memory Concentration Test results in a practice effect in Alzheimer's disease. AB - We analyzed short-term variation of Mini-Mental State Examination (MMSE) and Information-Memory-Concentration (IMC) Test scores in 39 patients with Alzheimer's disease (AD), tested four times over 6 weeks. Although analysis of variance had failed to show a significant "learning" effect or other trends, we reexamined the data using repeated measures models, with and without a learning effect. In the model without a learning effect, mean MMSE scores decreased minimally and mean IMC scores decreased by 0.84 points over 6 weeks. In the model that allowed a potential learning effect between the first and second test sessions, scores increased significantly, by 1.12 +/- 0.47 points for the MMSE and 1.04 +/- 0.43 points for the IMC Test. Patients' test scores predicted from the models had less variability than did their raw scores. The short-term practice effect, although small, should be considered in interpreting changes in scores, especially in therapeutic studies in AD. PMID- 8351010 TI - Phenotypic expression of X-linked dystonia-parkinsonism (lubag) in two women. AB - Lubag (X-linked dystonia-parkinsonism) has been considered a sex-linked recessive trait and has been mapped to the pericentromeric region of the X chromosome. We studied a 54-year-old man with lubag and two of his female first cousins. Genetic typing was carried out using X chromosome markers. Fluorodopa PET was performed on the man and one of the women. The man had moderately severe parkinsonism and dystonia. A 61-year-old female first cousin had mild left-sided dystonia and her 54-year-old sister had mild generalized chorea. Genetic typing data revealed that all three inherited an X chromosome with marker alleles strongly associated with lubag. Cytologic analysis did not reveal evidence of X chromosomal deletion. Fluorodopa PET in both the man and one affected cousin revealed reduced striatal uptake rate constants consistent with nigrostriatal involvement. These observations suggest that lubag may be a codominant disorder and that it is possible for women to be affected. PMID- 8351012 TI - Comparison of striatal 18F-dopa uptake in adult-onset dystonia-parkinsonism, Parkinson's disease, and dopa-responsive dystonia. AB - We studied six patients with adult-onset dystonia-parkinsonism (DYS-P) with 18F-6 fluoro-dopa (18F-dopa) positron emission tomography and compared their influx constants (Ki values) with those of six patients with classical childhood-onset dopa-responsive dystonia (DRD), 12 age-matched Parkinson's disease (PD) patients without dystonia, and 21 normal controls. The DYS-P group had significantly reduced mean caudate (67% of normal) and putamen (45% of normal) 18F-dopa uptake. These Ki values were similar to mean caudate and putamen Ki values obtained for the PD group. In contrast, the DRD group showed minor reductions in mean caudate (9%) and putamen (18%) 18F-dopa uptake when compared with normals. The mean caudate:putamen Ki ratio was 1.7 in the DYS-P group and 2.1 in the PD group. In the DRD and normal groups, the caudate:putamen ratios were close to unity. The findings of this study are that adult-onset DYS-P targets the nigrostriatal dopaminergic projections in a pattern similar to PD, with the putamen being more affected. This provides support for the hypothesis that DYS-P may be a phenotypic variant of Lewy body disease. DYS-P seems distinct from childhood-onset DRD, in which striatal 18F-dopa uptake is either normal or only mildly reduced. PMID- 8351013 TI - Single-photon emission computed tomographic investigation of patients with motor neuron disease. AB - To investigate the correlation between involvement of the CNS in motor neuron disease (MND) and neuroimaging abnormalities, we studied 18 patients with MND by single-photon emission computed tomography (SPECT) and MRI. Patients were divided into four groups according to the results of SPECT. Group 1 consisted of four patients with reduced isotope uptake in the frontal lobe, including the motor area, and in the anterior part of the temporal lobe; group 2 consisted of two patients with reduced isotope uptake in the motor area spreading to the adjacent frontal lobe; group 3 consisted of eight patients with reduced isotope uptake confined to the motor area; and group 4 consisted of four patients without reduced isotope uptake. We found dementia in group 1, borderline dementia in group 2, and no cognitive deficit in group 3 or four. MRI demonstrated enhanced T2-weighted signals along the pyramidal tract in eight patients, but this finding also existed in some control subjects. SPECT appears useful in identifying the location of cortical neuronal degeneration in patients with MND. PMID- 8351014 TI - Prevalence of myotonic dystrophy in Guipuzcoa (Basque Country, Spain). AB - Prevalence figures for inherited neuromuscular disorders are important both for health care planning purposes and for evaluating the need for DNA diagnostic services for eugenic approaches. We screened for the prevalence of myotonic dystrophy (MyD) through extensive inquiry of neurologic and primary health services of Guipuzcoa (Basque Country, northern Spain) between 1989 and 1991. Typical adult-onset and neonatal cases and relatives at risk; suffering from a partial syndrome, were included. In the latter, molecular typing was performed with DNA probes close to the MyD gene to demonstrate the MyD gene carrier status. The high prevalence detected (26.5 cases per 100,000 population) could be explained by methodological factors, but intrinsic factors, such as a possible founder genetic effect or the quick growth of the Guipuzcoa population since the last century may contribute to one of the highest MyD prevalence in the world. In the future, the methodological basis for epidemiologic surveys of MyD must combine molecular technology with more-extensive family inquiries. PMID- 8351015 TI - Acute elevation and recovery of intracellular [Mg2+] following human focal cerebral ischemia. AB - We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 +/- 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 +/- 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 +/- 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr+Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 +/- 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 +/- 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 +/- 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 +/- 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury. PMID- 8351016 TI - Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin. AB - Approximately 15% of patients with myasthenia gravis (MG) have thymus neoplasia. These MG with thymoma (MGT) patients show autoantibodies to striated muscle as well as autoantibodies to acetylcholine receptor. To characterize these thymoma associated muscle antigens, we cloned a number of immunopositive cDNAs by immunoscreening muscle cDNA libraries with sera from MGT patients. Analysis of the isolated cDNAs show that all share a common sequence encoding a distinct region of the titin gene. We expressed this main immunogenic region (MIR) of titin in Escherichia coli, and determined autoantibody serum titers directed against the obtained recombinant antigen in a variety of patients. We could detect titin MIR autoantibodies in 97% of sera from MGT patients but not in control sera from healthy blood donors. Therefore, expressed titin from the MIR of the molecule is a sensitive marker antigen for evaluating the presence of thymoma in MG. PMID- 8351017 TI - Variable distribution of mutant mitochondrial DNAs (tRNA(Leu[3243])) in tissues of symptomatic relatives with MELAS: the role of mitotic segregation. AB - We studied multiple different postmortem tissue samples from a woman and two of her daughters with the MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) tRNA(Leu(UUR)) mutation at nucleotide 3243 in mitochondrial DNA (mtDNA). All tissues examined were heteroplasmic for the mutation. The mean proportion of mutant mtDNAs in the mother's tissues (0.30 +/- 0.10) was significantly lower than that of each of her daughters' (0.76 +/- 0.11, p < 0.03, and 0.72 +/- 0.13, p < 0.001); there was no difference in the fraction of mutant mtDNAs between the daughters (p < 0.71). This difference in the mean proportion of mtDNA mutants between family members correlates with their clinical profiles; the mother had the latest onset of disease and lived longest, while the two daughters had a strikingly similar clinical course. In individual patients, the mean proportion of mutant mtDNAs was not different in tissues deriving from ectodermal, mesodermal, and endodermal germ layers. Variance in the mutant:wild type mtDNA ratio was normally distributed about the mean, both when all tissues were considered together and when different regions of the CNS were considered separately. Thus, the proportion of mtDNAs carrying the tRNA(Leu(3243)) mutation was not uniform in members of this pedigree and did not undergo rapid mitotic segregation along germ-layer divisions. These findings are consistent with the hypothesis that the overall proportion of mtDNAs carrying this mutation is primarily determined by segregation during oogenesis or early embryologic development and that random replicative (mitotic) segregation, subsequent to the establishment of primary germ layers, is responsible for the variation between tissues. PMID- 8351018 TI - Asymmetry of forearm rolling as a sign of unilateral cerebral dysfunction. AB - We compared the reliability of asymmetry of forearm rolling (rotation of one forearm around the other in front of the torso) as a sign of unilateral cerebral dysfunction with that of other standard clinical tests. We studied 62 patients with radiologically confirmed unilateral cerebral lesions and 20 control subjects with normal imaging. Asymmetric forearm rolling was the most sensitive indicator of unilateral hemispheric disease (85%). This simple test is a useful addition to the neurologic examination. PMID- 8351019 TI - Effect of cranial irradiation on seizure frequency in adults with low-grade astrocytoma and medically intractable epilepsy. AB - We report the effect of cranial irradiation on seizure frequency in five adults with unresected (biopsy-proven) cerebral hemisphere low-grade astrocytoma and medically intractable epilepsy. Seizures were refractory to standard antiepileptic drugs for 7 months to 27 years. Treatment with 5,400 cGy to 6,120 cGy focal radiation reduced seizure frequency by more than 90% in three patients (one of whom became seizure-free) and by more than 75% (but less than 90%) in one patient. One patient had no response. Brain CT or MRI showed a partial tumor response to radiation in three of the four patients with reduced seizure frequency. In three patients, the reduced seizure frequency continued to the most recent follow-up of 1 to 1.5 years. In the patient who became seizure-free, seizures recurred at 8.2 years and were associated with tumor progression. Irradiation can reduce seizure frequency in some patients with unresected cerebral hemisphere low-grade astrocytoma and medically intractable epilepsy. PMID- 8351020 TI - Seronegative, non-neoplastic acute cerebellar degeneration. AB - Five women are presented with a subacute pure pancerebellar syndrome of ataxia and dysarthria to emphasize that this illness may occur without anti-Purkinje cell or anti-Yo antibodies, or associated systemic cancer. The syndrome evolved over weeks or less and stabilized in four of the patients. Three had had a preceding infection and one, a rash, but there was no inflammatory response in the spinal fluid. Over the 5-year period during which these patients appeared in an individual general neurology practice, there was only one patient with paraneoplastic cerebellar degeneration. Despite the association of this syndrome with cancer, particularly in women, clinicians will still commonly confront the idiopathic variety. PMID- 8351021 TI - Anti-Ri-associated paraneoplastic neurologic disorder without opsoclonus in a patient with breast cancer. AB - A 59-year-old woman with breast cancer and anti-Ri antibodies developed a neurologic paraneoplastic disorder characterized by nausea, vomiting, vertigo, paresis of upward gaze, and gait ataxia, without opsoclonus. The absence of opsoclonus does not rule out the possibility of an anti-Ri-associated paraneoplastic neurologic disorder. PMID- 8351022 TI - Retinal disease masquerading as spasmus nutans. AB - Two children with congenital stationary night blindness were originally diagnosed as having spasmus nutans. Both children had the typical features of spasmus nutans including asymmetric nystagmus, head shaking, and torticollis. The diagnosis of congenital stationary night blindness was established only after each child underwent electroretinography. The nystagmus associated with retinal disease can mimic many of the features of spasmus nutans. Children suspected of having spasmus nutans should undergo complete ophthalmologic examination and electroretinography if they are myopic. PMID- 8351023 TI - Clinical trial of indomethacin in Alzheimer's disease. AB - In a 6-month, double-blind, placebo-controlled study, 100 to 150 mg/d indomethacin appeared to protect mild to moderately impaired Alzheimer's disease patients from the degree of cognitive decline exhibited by a well-matched, placebo-treated group. Over a battery of cognitive tests, indomethacin patients improved 1.3% (+/- 1.8%), whereas placebo patients declined 8.4% (+/- 2.3%)--a significant difference (p < 0.003). Caveats include adverse reactions to indomethacin and the limited scale of the trial. PMID- 8351024 TI - Hepatitis B transmission by neurologic pin testing. PMID- 8351026 TI - Hysterical hemiparesis accompanying Bell's palsy. PMID- 8351025 TI - 'Essential tremor' and CAG repeats in the androgen receptor gene. PMID- 8351027 TI - Ciprofloxacin-induced complex partial status epilepticus manifesting as an acute confusional state. PMID- 8351028 TI - Pentoxifylline-induced musical hallucinations. PMID- 8351029 TI - Neurology in family practice. PMID- 8351030 TI - Aging and Alzheimer's. PMID- 8351031 TI - Serotonin, depression, and PD. PMID- 8351032 TI - Centrum ovale infarcts. PMID- 8351033 TI - Neurolymphomatosis. PMID- 8351034 TI - Neurolymphomatosis. PMID- 8351035 TI - Late-onset MS. PMID- 8351036 TI - Diagnosis of PD. PMID- 8351037 TI - Withholding therapy. PMID- 8351038 TI - Withholding therapy. PMID- 8351039 TI - Stress and hemorrhages. PMID- 8351041 TI - Delayed hemorrhage. PMID- 8351040 TI - Delayed hemorrhage. PMID- 8351042 TI - A longitudinal study of infections and injuries of Ranger students. AB - Causes of medical attrition and their implications for medical support for the U.S. Army Ranger course are considered, based on data collected from 190 students in a summer class. In the second half of the course, an increase in documented infection rates, notably cellulitis of the lower extremities and Streptococcus carriage prevalence, coincided with indications of compromised immune function. The authors suggest that aggressive treatment in the field, including liberal use of antibiotics, and periodic examination of each student by medical personnel are critical factors which will minimize medical attrition and ensure safe participation of soldiers in this and other stressful and sustained field exercises. PMID- 8351044 TI - Helping the helpers: family support for social workers mobilized during Desert Storm/Shield. AB - This study identifies the types of social support available to the families of social work officers activated during Operation Desert Storm/Shield and determines which social supports were utilized by these families and the degree of perceived satisfaction with those social supports. This is a post-event assessment on a one-time basis. A Social Support Questionnaire was sent to the spouses of all activated Social Work Officers. Findings suggest no correlation between amount of social support and perceived effectiveness. Findings also suggest a need to assist families of military social work officers with informal and formal social support connections. PMID- 8351045 TI - Clinical practice guidelines: enhancing quality of care. PMID- 8351043 TI - Effect of chewable antiplaque preparation on plaque and gingival index scores in military academy cadets during their two-week winter camp. AB - Dental emergencies in the military are mostly due to infections of the teeth. Practising normal oral hygiene is very difficult during terrain maneuvers, for example. Therefore, a chewable antiplaque preparation was developed to inhibit the growth of dental plaque. The preparation contains chlorhexidine, fluoride, and xylitol and it can be easily added to the soldier's kit. This paper presents results on the efficacy of the preparation in maintaining satisfactory oral hygiene in military academy cadets during a 2-week winter camp. The preparation was found significantly more effective in reducing gingivitis than conventional brushing of the teeth (p < 0.001). PMID- 8351046 TI - Evolution of America's pioneer bacteriologist: George M. Sternberg's formative years. AB - George M. Sternberg, 1838-1915, M. D., USA, activated modern American bacteriology. He produced the first general bacteriology book in the English language in 1880. His first publications on chemical disinfection (1879) preceded Koch's Sternberg discovered the pneumococcus (1880) before Pasteur did and speculated about phagocytosis (1881) before Metchnikoff. As an experimentalist and author, Sternberg stood "at the head of the American school of working bacteriologists" by the early 1880s. Our essay on Sternberg's evolution as a scientist explains what motivated him and why his early achievements as a bacteriologist, praised by contemporaries, have been underestimated more recently. PMID- 8351047 TI - Cold weather field evaluation of the 18-Man Arctic Tray Pack Ration Module, the meal, ready-to-eat, and the Long Life Ration Packet. AB - The Army Field Feeding System was evaluated for its ability to provide adequate nutrition and hydration during a 10-day cold weather field exercise. Soldiers consumed the 18-Man Arctic Tray Pack Ratio Module with either a wet-pack (Meal, Ready-to-Eat) or a dehydrated (Long Life Ration Packet) individual ration. Both feeding regimens were acceptable, meeting protein and micronutrients requirements. However, the soldiers consumed only 70% of their energy requirement, thus losing an average of 0.9% of body weight. This weight loss, although not excessive, underscores the importance of maintaining an adequate food intake during extended cold weather military field operations. PMID- 8351049 TI - A one-year look at the impact of cholesterol screening, education, and counseling. AB - During 1989 and 1990, we offered cholesterol screening in conjunction with National Medical Laboratory Week. The proportions of subjects categorized as hypercholesterolemic decreased in 1990 in each eligibility category except family members. Active duty subjects decreased from 39% to 30%, retired subjects from 60% to 55%, and civilian subjects from 51% to 43%. These changes were also reflected in significant decreases in the mean cholesterol levels for retired and civilian subjects. The data suggest a downward trend that we hope will continue with active screening, education, and counseling. PMID- 8351048 TI - Children's reactions to the Desert Storm deployment: initial findings from a survey of Army families. AB - Psychological symptom profiles were obtained on 1,601 children of soldiers deployed during Operation Desert Storm (ODS). The profiles were obtained from reports of the parents who stayed at home with the children. Certain symptoms such as sadness were common, but very few parents considered their children's problems serious enough to require counseling. The strongest predictor of children's receiving counseling during ODS was a previous history of being in counseling for emotional problems. PMID- 8351050 TI - Indications for internal stenting in intestinal obstruction. AB - Internal stenting (sutureless plication) for intestinal adhesions was performed operatively in 16 patients. Subsequent recurrent obstruction occurred in four patients. Other complications occurred in three patients and included retained tube, jejunostomy-site abscess, and intestinal fistulization. Four patients died for an in-hospital mortality of 25%. Internal stenting for adhesions should be used cautiously. Its use should probably be restricted to the setting of severe adhesive small bowel obstruction particularly when numerous enterotomies are incurred during the course of adhesiolysis. PMID- 8351051 TI - The effects of alcohol and tobacco use on troop readiness. AB - Prior studies have documented the ill effects of cigarette smoking on soldier athletic performance. We examined the effects, if any, of cigarette smoking and alcohol use on troop readiness. A group of 510 soldiers was examined. They answered an initial questionnaire and then were followed in sick call for a 2 month period. The results of the study confirmed that cigarette smoking impacted adversely on athletic performance. However, we were unable to quantitate increased time off or away from duty as a result of cigarette smoking and alcohol use. PMID- 8351052 TI - NAMRU-3: forty-six years of infectious disease research. AB - The United States Naval Medical Research Unit No. 3 (NAMRU-3), Cairo, Egypt, has been in continuous operation studying infectious diseases of military importance since its establishment in 1946, even during the lapse in diplomatic relations from 1967-1974. Other overseas research laboratories of the Naval Medical Research and Development Command include NAMRU-2 in Jakarta, Indonesia, with a detachment in Manila, and the Naval Medical Research Institute Detachment Lima, Peru. Comparable U.S. Army overseas research laboratories are located in Thailand, Brazil, Korea, and Kenya. Department of Defense overseas laboratories conduct research on infectious diseases endemic to their respective geographic regions which could adversely impact on the health of deployed military forces. This article describes the history of one such laboratory, NAMRU-3, and the important infectious disease research it conducts to enhance the health of military forces deployed to its strategic geographical region of the world. PMID- 8351053 TI - Association between an excessive body mass index and coronary heart disease risk factors in military personnel. AB - The purpose of this study was to document the extent of coronary heart disease (CHD) risk factors in military personnel (412 men, 50 women) classified as seriously overweight (body mass index [BMI] 27.0-29.9 kg/m2) or obese (BMI > or = 30 kg/m2) and to evaluate the utility of the BMI to discriminate among individuals with an adverse CHD risk profile. Mean body weight and BMI greatly exceeded Canadian norms, whereas mean heights were average. There were low but significant correlations between BMI and resting and submaximal exercise (stage A of the Canadian Aerobic Fitness Test) heart rates and blood pressures, while the correlation with predicted VO2max was negative. Except for blood glucose level (GLU) in men, there were no significant correlations between BMI and various biochemical indices. Compared to "overweight" men, the percentage of "obese" men with abnormal values for risk factors were higher, particularly for an adverse exercise blood pressure response and low predicted VO2max. In summary, the correlations between BMI and the various CHD risk factors, except for GLU and the exercise parameters, were minimal or moderate at best. It was concluded that in overweight and obese individuals, BMI does not appear to be a particularly sensitive indicator of body fat and risk factors. PMID- 8351054 TI - Pharmacotherapy for recently evacuated military casualties. AB - In late 1990 during the massive Operation Desert Shield/Storm (ODS) deployment of United Nations troops, the VA/DoD Joint Contingency Plan was activated. Worst case scenarios projected tens of thousands of medical evacuees from the Persian Gulf and predicted that U.S. Military Communication Zone and CONUS bed capacity would quickly be saturated. As a result, a massive educational program was rapidly implemented to prepare 80 VA hospitals to receive ODS personnel within 1 3 weeks of their evacuation from battalion aid stations or other front-echelon medical facilities. This article was written as part of this educational effort. Noting that there were no published articles on pharmacotherapy for recently evacuated military casualties, the authors wrote the present manuscript for inclusion in the ODS Clinical Packet prepared by the VA's National Center for PTSD and circulated to VA mental health professionals. Since the published literature still lacks an article on this subject and since we believe that our comments on pharmacotherapy apply to survivors of most acute traumatic events, we present our observations and recommendations with the hope that they may be useful to military, VA, and civilian practitioners. PMID- 8351055 TI - Antepartum diagnosis of arthrogryposis associated with trisomy 18. AB - The discovery of a fetal abnormality during ultrasonography is a widely acknowledged indication for genetic amniocentesis. We present a case in which the early diagnosis of severe arthrogryposis led to the diagnosis of trisomy 18. PMID- 8351056 TI - A persistent left lower lobe infiltrate and chronic cough following chest wounds sustained in Vietnam twenty-four years earlier. PMID- 8351057 TI - Spine injuries in combat troops--Panama, 1989. AB - Operation Just Cause was until recently the largest American combat operation since Vietnam, and remains the largest nighttime parachute operation since World War II. All 252 casualties were airlifted to San Antonio, Texas, for medical treatment. Greater than 80% sustained orthopedic injuries. Sixteen patients were admitted for injuries to the back or neck. Three of the four patients with significant fractures or fracture-dislocations were paraplegic. Two of the three patients with gunshot wounds to the back required extensive reconstruction for wound management. In addition to the 252 casualties, there were 23 fatalities, among whom 7 suffered major injuries to the spine. Spine injuries represented the most significant source of long-term morbidity among those soldiers wounded in combat in Panama, and were common among the fatalities. Noteworthy in these cases was the high percentage of severe neurologic injuries in patients with significant fractures (75%), particularly fractures associated with gunshot wounds. Also of interest were the cases of major soft tissue injury associated with high-velocity gunshot wounds (66%) and the extensive soft tissue surgery needed to treat these injuries. PMID- 8351058 TI - Parathyroid carcinoma: case report. AB - Parathyroid carcinoma is a rare entity, representing less than 1% to 5% of patients with primary hyperparathyroidism. Parathyroid carcinomas are often symptomatic, have markedly elevated calcium levels, have palpable masses, are equally distributed between the sexes, and present 10 years younger than their benign counterparts. Parathyroid carcinoma is often undiagnosed preoperatively, suspected intraoperatively, and only confirmed postoperatively. When diagnosed, the treatment of choice is an en-bloc resection of the tumor. PMID- 8351059 TI - [Hysteroscopic evaluation of female infertility]. AB - Three-hundred-seventy-one infertile patients underwent hysteroscopic evaluation. The test was performed in an outpatient setting without any form of anesthesia. A comparison has been made among this technique, the hysterosalpingography and ultrasounds: hysteroscopy showed to be more accurate in the evaluation of intracavitary pathology, because of its capability to obtain a direct view of the uterine cavity. We can evaluate hysteroscopically nature, dimension and localization of the lesions. However HSG remains the best technique for the study of tubal factors of infertility. We think that hysteroscopy should be used besides other diagnostic methods, in order to obtain a better evaluation of the infertile patients. PMID- 8351060 TI - [Pre-menopausal dysfunctional menometrorrhagia: therapeutic approach]. AB - Approximately 10% of premenopausal women suffer from dysfunctional menometrorrhagia. The correct therapeutic approach to this pathology above all requires a precise diagnostic framework. For this purpose the doctor can employ a number of laboratory and instrumental tests, both invasive and non-invasive, in order to differentiate the dysfunctional forms from those supported by organic pathologies or non-gynecological diseases. Once the diagnostic iter has been completed, the choice of therapy can be directed towards surgical or medical treatment; the latter may be symptomatic or causal. This review focuses on the most commonly used treatments for dysfunctional menometrorrhagia in premenopausal women and proposes clinical protocols for a correct diagnostic and therapeutic approach. PMID- 8351061 TI - [Role of the second look in ovarian neoplasia]. AB - The indications for the execution of a second look in patients affected with ovarian cancers and the possible benefits of this procedure, related to the stage of the neoplastic disease, are examined. The second look, at first largely used in patients in which had been performed adjuvant chemotherapy with drugs containing platinum and with no evidence of residual disease, has been later strongly criticized and the effective usefulness of this invasive procedure discussed. At the moment, we think that the indications for its execution are still large because with the second look it is also possible to put into the abdomen a catheter which can be used for locoregional chemotherapy and there is now the opportunity to perform this procedure also in video-laparoscopy. PMID- 8351062 TI - [Minimal celiosurgery in endometriosis]. AB - After a brief consideration of the recent therapeutic approaches to endometriosis, the Authors suggest their laparoscopic method which includes drainage by aspiration of the endometrioma using a wide biopsy, followed by careful lavage of the cystic cavity and abdomen and partial thermocoagulation of the same capsule and any visible residual implants. The patients were admitted for infertility in 47% of cases, chorionic pelvic pain in 16% of cases and pelvic mass in 10%. By using this procedure symptomatic relief was seen in 72% of cases and a pregnancy rate of 81% obtained with encouraging results even in moderate and severe endometriosis. PMID- 8351063 TI - [Modifications induced on thrombin and plasmin activity by voluntary interruption of pregnancy]. AB - Pregnancy is characterized by plasmatic variations of coagulative factors' concentration and by different haemostatic-fibrinolytic balance. At present it is possible, with EIA methods, to measure fibrinogen (FgDP) and fibrin (FbDP) degradation products with precision and accuracy, as direct indexes of fibrinolysis and the thrombin-antithrombin III complex (TAT) as indirect index of thrombophilia. We have considered the course of those indexes in 61 pregnant women within the tenth week of gestation, before and after voluntary pregnancy interruption (VPI) resulted without complications. The results don't show any peculiar variation of the examined parameters between the pregnant women before VPI and a control group. Comparing the basal data with those obtained three hours after VPI, all indexes are increased, particularly FbDP. After 24 hours the concentration of FgDP, FbDP and TDP decreased in comparison with the three hours control drawing, nevertheless staying higher than the values obtained in the basal drawing. The evolution of FDP and of TAT, in our study, points out that, in the first weeks of pregnancy, the haemostatic-fibrinolytic balance does not differ significantly from the physiological balance. Three hours after VPI fibrinolytic mechanisms prevail as regards the fibrinogenolytic ones. TAT increases after 3 hours and returns to the rules after 24 hours, proposing itself as an indirect index of thrombinic activation and as a direct index of antithrombinic activity. PMID- 8351064 TI - [Treatment of endometrial hyperplasia with Goserelin depot, an LH-RH analog]. AB - Nineteen patients with simple endometrial hyperplasia presenting metrorrhagia or menometrorrhagia were treated with 4 injections of Goserelin depot, one every 4 weeks. 12/19 patients were refractory after previous medical therapy. The treatment with Goserelin depot resulted in a complete remission of the symptoms, occurring within the first month of treatment and still present after a median follow-up of 12 months, and in the normalization of the histological profile. No patient experienced clinically relevant side effects. PMID- 8351065 TI - [Meigs syndrome with bilateral hydrothorax]. AB - The co-existence of pelvic tumor, hydrothorax and ascites has been known since the last century. The features of this disease were described by Meigs and Cass in 1937; in the same year Roads named it Meigs syndrome. According to the original description this syndrome only included, as pelvic involvement, an ovarian neoplasm; at present it is accepted that hydrothorax and the ascites can also be associated with a uterine tumor, like a fibroma. The existence of either an ovarian or a uterine neoplasm distinguishes the typical Meigs syndrome from a pseudo-Meigs syndrome. The most likely pathogenesis of Meigs syndrome ascribes the formation of the peritoneal and pleural effusion to the filtration of interstitial fluid in the peritoneum through the tumor capsule, and the diffusion to the pleural space, generally at the right side, through the diaphragm lymphatic vessels and the foramen of Bochdalek. Dockerty reported that at least 40% of ovarian tumors had a diameter of more than 6 cm when associated with hydrothorax and ascites. The entity of pleural and peritoneal effusion can be moderate or massive. The effusions generally derive from a transudative process, but they can occasionally contain blood cells. The connection between the pelvic tumor and the effusion is demonstrated by the regression of the latter when the neoplasm is excised. When the pelvic tumor has an ovarian location it derives from the connective tissue of the hilus, it appears during fertile age and has a slow growth, the clinical signs becoming evident in elder age. PMID- 8351066 TI - [Acute pancreatitis in pregnancy]. AB - This paper describes a case of acute pancreatitis occurring in a patient immediately after delivery and in primigravida. The patient had a family case history of dyslipidemia (Type IV). The pregnancy had been complicated by preeclampsia treated at home with nifedipine tablets (one tablet three times a day) with good results on pressure values; lipidic values were high despite dietary measures taken. The baby at birth weighed 3830 g after physiologic labour and a natural delivery. Acute pancreatitis was diagnosed after observation of epigastralgia with irradiation on the left shoulder, vomiting, symptoms of acute abdomen such as sweating, increased pulse rate, hypotension, abdominal pain on palpation, and absence of peristalsis. An analysis of the blood showed high levels of amylase and hyperglycemia, an increase in XDP, and leucocytosis. Instrumental tests such as pancreatic echography revealed an increase in pancreatic volume, uneven structure of the parenchyma and higher levels of liquid in the peritoneum. The patient was moved to intensive-care, a nasal gastric probe inserted, hydroelectrolytic treatment was begun, vital functions monitored, pain kept under control by medical therapy, and antibiotics administered. Subsequent tests showed an improvement in the parameters of pancreatic functions (amylase, lipase, calcium hematic) and their gradual return to normal values. The computerized tomography of abdomen additionally revealed the presence of pancreatic pseudo-cysts and effusion of peritoneal liquid near the right kidney. The patient was discharged after two weeks in the surgical ward. There are many caused of acute abdomen during and immediately after pregnancy, and one of these is acute pancreatitis, though rare (occurring between 1:3800 and 11.467 according to Rabkin).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351067 TI - Nurses in the front lines. PMID- 8351069 TI - We've come a long way, maybe. Women's health and the 103rd Congress. PMID- 8351070 TI - The term is "health care". PMID- 8351068 TI - Nursing & society--the unfinished agenda for the 21st century. PMID- 8351071 TI - Nursing education: staying on track. PMID- 8351072 TI - An immodest proposal. PMID- 8351074 TI - The secret Munchausen epidemic. PMID- 8351073 TI - Medical hucksterism is still with us. PMID- 8351076 TI - Baccalaureate and master's degree programs in nursing accredited by the NLN 1993 94. PMID- 8351075 TI - President's message: an extraordinary moment in history. PMID- 8351077 TI - NMR of proteins. PMID- 8351078 TI - The biosynthesis of shikimate metabolites. PMID- 8351079 TI - Biological variation of microbial metabolites by precursor-directed biosynthesis. PMID- 8351080 TI - Stevioside and related sweet diterpenoid glycosides. PMID- 8351081 TI - Direct and indirect care in a multidisciplinary collaborative practice model. PMID- 8351082 TI - Women and health care. PMID- 8351083 TI - Marie Osborn and the Salmon River Emergency Clinic. PMID- 8351085 TI - Combination sulfonylurea and insulin therapy in non-insulin-dependent diabetes mellitus. AB - Clinicians are frequently faced with treating non-insulin-dependent diabetics (NIDDM) who do not exhibit optimal glycemic control on maximal dosages of oral sulfonylurea agents or large dosages of insulin. Sustained hyperglycemia is implicated in the onset and progression of retinopathy, nephropathy, and neuropathy. Recent studies also suggest that hyperinsulinemia contributes to hypertension and altered lipid levels. Hence, the maintenance of euglycemia with minimal circulating insulin concentrations is the prime goal of therapy. Most studies document that the efficacy of combination therapy requires smaller insulin doses, enhances glycemic control without adverse effects on body weight or lipids, and decreases hypoglycemic episodes compared with insulin monotherapy. Therefore, combination therapy may be the optimal therapeutic option in NIDDM clients manifesting secondary failure to oral agents or insulin resistance. PMID- 8351084 TI - Intensive insulin therapy in insulin dependent diabetes and combination therapy. AB - Intensive insulin therapy (IIT) and combination therapy using sulfonylurea and insulin are two insulin regimens being used more frequently to improve glycemic control. For those patients with insulin-dependent diabetes, IIT or multiple daily injection therapy mimics normal pancreatic function by its timing of insulin delivery. The improvement in glycemic control carries with it the risk of a two- to threefold increase in episodes of hypoglycemia. For those with non insulin-dependent diabetes, combination therapy attempts to provide a bridge between maximal dose oral hypoglycemic agents and aggressive insulin therapy. Although this therapy remains controversial, it has proved useful in select patient groups. This article discusses the rationale for IIT, and its implementation. Variables that affect IIT are discussed. The combination therapy section provides guidelines for patient selection and insulin protocols for evening insulin administration. The health care provider is familiarized with these alternative therapies and their successful applications. PMID- 8351086 TI - Early detection and intervention for hazardous ethanol use. AB - Alcohol use is prevalent throughout our culture and produces costly, staggering results. Excessive alcohol consumption has extensive implications for the user's health, economic well-being, psychological equilibrium, and family and social relationships. The resulting consequences add to the spiraling health care costs encountered in the United States. Recognition of the pervasiveness of this problem is key to primary prevention. This article seeks to encourage clinicians to identify high risk alcohol users. Health care providers have potentially a great impact on clients and are in a position not only to identify alcohol abusers early in the course of their alcohol use, but also to mobilize interventions and make referrals. Parameters for recognizing progression of use and evaluating the impact of regular consumption are discussed and a protocol for rapid, accurate assessment are presented. Low cost interventions will be suggested as well as referral guidelines. PMID- 8351088 TI - The escalator phenomenon and health care. PMID- 8351087 TI - Interpretation of laboratory values in older adults. AB - This article describes age-related physiologic changes in the older adult and the effect of these changes, if any, on commonly ordered laboratory tests. As reported in selected research studies and literature reviews, some laboratory parameters change minimally or not at all with age, still remaining within recommended reference ranges, while others are altered with age. Misinterpretation of an abnormal laboratory value as an aging change can lead to underdiagnosis and undertreatment in some instances (such as anemia). Failure to appreciate age-related changes can lead to overdiagnosis and overtreatment in others (such as hyperglycemia). The results from ongoing national studies are needed to establish uniform older adult reference intervals. PMID- 8351089 TI - Scleral buckle removal following retinal reattachment surgery: clinical and microbiologic aspects. AB - Scleral buckle infection following retinal reattachment surgery is infrequent but not rare. We identified 45 cases among approximately 3000 scleral buckling procedures performed at our institution between July 1, 1985 and July 1, 1991. The scleral buckle was exposed in all 45, and the subsequent microbiologic culture was positive in 33. The most common causative organism was coagulase negative staphylococci (17 of 33 cases with positive cultures). Risk factors for an adverse outcome included positive culture, preoperative vision < or = 20/200, and preoperative retinal detachment. Broad spectrum antibiotics covered organism sensitivity profiles in 16 of the 18 cases tested. Prompt removal of infected buckles and treatment with broad-spectrum topical antibiotics are important for maintaining vision. PMID- 8351090 TI - Combined extracapsular cataract extraction, posterior chamber intraocular lens implantation, and pars plana vitrectomy. AB - The surgical management of coexisting cataract and vitreoretinal disease has been controversial, particularly for eyes with a history of proliferative diabetic retinopathy (PDR) or chronic uveitis. We retrospectively studied the results of combined extracapsular cataract extraction (ECCE), posterior chamber intraocular lens (PC-IOL) implantation, and pars plana vitrectomy in 20 eyes of 16 patients. The indications for combined vitrectomy included dense, nonclearing vitreous hemorrhage attributed to PDR in 10 eyes, age-related macular degeneration in 2, and trauma in 1. The remaining 7 eyes had pars plana vitrectomy to remove inflammatory vitreous cell and debris associated with chronic uveitis. Follow up ranged from 4 to 32 months (average, 17.4 months). Visual acuity improved in 19 eyes (95%)--to 20/100 or better in 12 (60%). The improvement ranged from 1 to 13 Snellen lines (average, 4.9 lines). Postoperative visual acuity improvement averaged 7.5 Snellen lines for eyes with chronic uveitis, 7.0 lines for those with age-related macular degeneration, and 3.3 lines for those with a history of PDR. Postoperative visual acuity was less than 20/100 in 8 eyes (40%). In most cases, these latter results were attributed to macular changes associated with the underlying ocular disease. Our results confirm previous studies that have shown that combined ECCE/PC-IOL implantation and pars plana vitrectomy is a well tolerated surgical procedure for diabetics, which can provide clear anterior and posterior segment media. In addition, our results suggest that this combined procedure can be useful in restoring vision in certain eyes with uveitis in the short-term postoperative period. PMID- 8351091 TI - Intraocular dexamethasone penetration via subconjunctival or retrobulbar injections in rabbits. AB - Using high-performance liquid chromatography, we compared tissue levels of dexamethasone in the aqueous, vitreous, retina, and choroid of rabbits, 1 and 4 hours following subconjunctival or retrobulbar injection. One hour following injection, dexamethasone levels in all of these tissues were similar in both the subconjunctival and retrobulbar groups. Four hours following injection, the concentrations in the two groups also were similar, except in the choroid, in which the subconjunctival injection yielded significantly lower dexamethasone levels than the retrobulbar injection. Tissue steroid levels were comparable ipsilateral and contralateral to the injected eyes in both treatment groups after 4 hours, except in the retina, in which the levels were lower in the contralateral eye after subconjunctival injection. These data suggest that dexamethasone absorption and delivery is predominantly hematogenous following both subconjunctival and retrobulbar injection, especially in highly vascular tissues, such as the choroid. Hematogenous delivery of dexamethasone appears to peak earlier in the choroid and presumably in other intraocular tissues following subconjunctival injections, while retrobulbar injections provide more steady, long-term delivery. PMID- 8351092 TI - Unilateral lateral rectus recessions in exotropia. AB - For the past several years, we have been performing unilateral lateral rectus recessions in patients with small- to moderate-angle intermittent or constant exotropia. We report a 73% success rate in 45 patients undergoing 6- to 10 millimeter unilateral lateral rectus recessions in exotropia with a minimum of 6 months' follow up. The success rate increased to 89% for patients under 4 years of age. The advantages of this procedure include operating on only one eye and virtual elimination of overcorrections, thereby preventing early postoperative consecutive esotropia, which occasionally can result in amblyopia or diminished stereopsis in very young children. PMID- 8351094 TI - Eye growth after cataract extraction and intraocular lens implantation in children. AB - We studied the effect of cataract extraction and intraocular lens (IOL) implantation (14 unilateral and 2 bilateral cases) on eye growth in 16 children. Visual acuity, refractive power, axial length, corneal curvature, and anterior chamber depth in both the operated and unoperated eyes were measured before and after surgery. The operated eyes tended to become myopic (maximum, -11.00 diopters). However, though the axial length of two eyes increased significantly after surgery, there was no significant difference between the postoperative increase in axial length in the operated and in the unoperated eyes. The anterior chambers of the unoperated eyes tended to be deeper. We suggest that the tendency to become myopic in the operated eyes occurred because, as axial length increases with growth, the proportion occupied by the vitreous body, ie, the part posterior to the IOL, also increases. PMID- 8351093 TI - Reformation of the anterior chamber following trabeculectomy. AB - Sixteen eyes requiring surgical reformation of the anterior chamber (AC) in our Unit from December 1987 to August 1991 were studied retrospectively to determine the incidence of the problem in our hospital and to evaluate the operative measures used to restore the AC. The mean preoperative AC depth of these 16 eyes was 1.92 mm (range, 1.50 to 2.50 mm). Nine had a history of angle-closure glaucoma. Poor surgical technique was a contributing factor in the development of a flat AC in 3. Of the remaining 13 eyes, 11 had a trabeculectomy with a fornix based, and 2 with a limbus-based, conjunctival flap. Wound leaks occurred in 10 eyes with fornix-based flaps, but in none of the eyes with limbus-based flaps. Factors associated significantly with the development of flat AC following trabeculectomy were: a preoperative shallow AC, a history of angle-closure glaucoma, and the use of a fornix-based conjunctival flap. Avoiding wound leakage when performing trabeculectomy in eyes with a shallow AC or a history of angle closure glaucoma by using a limbus-based flap may help prevent postoperative flat AC. PMID- 8351095 TI - A closed chamber technique for repair of iridodialysis. AB - We have developed a surgical technique for repair of traumatic iridodialysis, in which a 25-gauge hypodermic needle is used to place a 10-0 polypropylene suture in sewing-machine fashion through a closed anterior chamber. The technique also can be modified to secure a posterior capsule with a partial zonular dialysis, such as may occur during phacoemulsification or cortical clean-up. PMID- 8351097 TI - Use of a silicone sheet for delayed adjustable strabismus surgery. AB - Adjustable strabismus surgery sometimes fails because of changes in the angle of deviation developing a few days after surgery. A thin silicone sheet placed between the muscle and sclera prevents postoperative adhesions between these tissues, allowing adjustment to be delayed for up to 11 days after surgery. Once the final adjustment is made, the silicone sheet is removed. PMID- 8351096 TI - A new technique for combined cataract/glaucoma procedures in patients on chronic miotics. AB - We describe a combined cataract/glaucoma procedure for patients on chronic miotics that includes small-incision phacoemulsification to provide increased predictability of visual outcome and early visual rehabilitation, and an inferior pupilloplasty to facilitate intraoperative visualization. To date, 42 procedures have been performed with excellent results. Complications, although minimal, have included iridolenticular/iridocapsular adhesions, diplopia, rupture of 10-0 polypropylene sutures, peripheral anterior synechia, hyphema, and fibrinoid aqueous. PMID- 8351098 TI - Size of the lens nucleus separated by hydrodissection. AB - We measured the extracted central nucleus (diameter and thickness) of 88 eyes (average patient age, 72 years) undergoing extracapsular cataract extraction (ECCE). The average diameter was 6.51 +/- 0.75 mm; the average thickness, 2.96 +/ 0.33 mm. Since the average lens diameter is approximately 10 mm, a corneoscleral incision of 7 to 8 mm in chord length should be sufficient for its removal in most ECCE cases. Accumulation of these data and further analysis correlating them with age and degree and type of cataract in larger series will be useful in determining the smallest possible incision size required for individual patients. PMID- 8351099 TI - The lower-lid retractors in congenital entropion and epiblepharon. AB - A case of congenital entropion is presented in which the lower-lid crease was lost during entropion surgery, yielding a postoperative condition resembling an epiblepharon. The case suggests that deficiencies in the lower-lid retractor fibers are a key factor in the pathogenesis of both congenital entropion and epiblepharon. PMID- 8351100 TI - Orbital retractors for posterior segment surgery. AB - Successful retinal detachment surgery is greatly aided by proper visualization of and access to the intended surgical field. Two retractors, one having a single blade and the other a double blade, have been developed to aid retinal detachment surgery. PMID- 8351101 TI - Eye movement restrictions after Molteno implant surgery. PMID- 8351102 TI - Perfluoroperhydrophenanthrene (Vitreon) is radiopaque. PMID- 8351103 TI - Adjunctive viscoelastic therapy for postoperative ciliary block glaucoma. PMID- 8351104 TI - The use of fibrin glue in mucous membrane grafting of the fornix. PMID- 8351105 TI - Let's say what we cut. PMID- 8351106 TI - Detector response and exposure control of the RadioVisioGraphy system (RVG 32000 ZHR). AB - The RadioVisioGraphy system (RVG 32000 ZHR) was studied with respect to some physical properties including the precision and linearity of the exposure control and the detector response to x-rays. The x-ray unit was found to yield repetitive exposures that are precisely controlled by the CCX timer. A "preheat" and an "after exposure" period were noticed, and their resulting x-ray exposures were measured. Two RVG detectors were compared for their responses with x-rays. The differences between the detectors were insignificant. However, inhomogeneous detector responses were found in both of the detectors; with the same exposure, the central parts of the detectors yielded lower pixel values than the peripheral parts. A calibration equation was developed to correct for the inhomogeneity. PMID- 8351107 TI - Microbiologic contamination during dental radiographic film processing. AB - This study investigated microbiologic contamination of an automatic dental radiograph processor and daylight loader during a week of simulated clinical use. Pure cultures of Candida albicans, Streptococcus pneumoniae, Staphylococcus aureus, or Klebsiella pneumoniae were used to contaminate 320 vinyl intraoral radiograph packets. Each end of the films was deliberately contaminated during opening. These films and 24 uncontaminated control films were processed. Daylight loader ports, inlet and outlet rollers, fixer and developer samples, and 12 processed films were cultured daily. To simulate a weekend, the processor sites were cultured during 72 hours of inactivity after the contaminated runs. The results showed that contamination of the processor and daylight loader occurred and remained even after 48 hours of inactivity. Films remained contaminated after processing. In addition, cross-contamination of films occurred in the processor. PMID- 8351108 TI - Dense bone island. A review of 107 patients. AB - The dense bone island is an asymptomatic radiopacity of unknown origin and is known under many synonyms when it occurs in the jaw. This article discusses 113 dense bone islands in 107 patients with a review of the literature and comparison with previous reports. The average age of the patient at discovery was 36 years with a women to men ratio of 2:1. The mandible was involved in 109 of the 113 DBIs, with only 4 in the maxilla. The most common site affected was the mandibular first molar region, the premolar region was the second most common site affected. Resorption occurred in 11 (9.7%) cases, the first permanent molar was the most commonly affected. PMID- 8351109 TI - Transposition and microdontia. PMID- 8351110 TI - Vertical root fracture. PMID- 8351111 TI - Multiple impacted teeth in the maxilla. PMID- 8351112 TI - Radiographic artifact mimicking root fracture. PMID- 8351114 TI - A new method for drain stabilization. PMID- 8351113 TI - Recurrent giant cell reaction to residual Proplast in the temporomandibular joint. AB - Exuberant foreign-body inflammatory reaction to polytetrafluoroethylene implants of the temporomandibular joint, marketed as Proplast-Teflon implants, has been widely recognized. Presently, removal of these implants is generally advised. Extensive damage of the joint and surrounding structures has been reported, including severe bony degeneration, perforation into the middle cranial fossa, and cerebrospinal fluid leak. However, recurrent foreign-body giant cell reaction, presumably as a result of residual Proplast material, has not been reported. We review our experience with Proplast-Teflon implant removal from 112 joints in 71 patients over a 6-year period, including four joints with recurrent giant cell reaction at various times after removal. Emphasis is placed on the phenomenon of recurrence and on microsurgical techniques to facilitate implant removal. PMID- 8351115 TI - More on the contraindications to vasoconstrictors in dentistry. PMID- 8351116 TI - Osteomyelitis of the mandible in Tehran, Iran. Analysis of 88 cases. AB - This study involved 88 cases of different types of osteomyelitis of the mandible. Sixty-nine patients had osteomyelitis after trauma, eight patients after radiotherapy, six after dental infection, and six had other causes. Thirty-three patients had septicemic infection. Multiple types of aerobic and nonaerobic microorganisms were isolated from the infection sites. Types of treatment and their results are discussed. PMID- 8351117 TI - Epstein's syndrome. Implications for oral surgery. AB - Epstein's syndrome is a rare inherited disorder that appears principally as nephritis and deafness with thrombocytopathic thrombocytopenia producing a bleeding tendency. Management of the disorder for oral surgical procedures is discussed and highlighted by a case report. PMID- 8351118 TI - Comparative trial of fluconazole and amphotericin in the treatment of denture stomatitis. AB - The efficacy of fluconazole and amphotericin in the management of denture stomatitis was investigated in a comparative trial. Patients were assessed clinically, hematologically, and mycologically at the time of entry into the study and at 1, 4, and 12 weeks thereafter. A total of 29 patients were selected at random to receive 50 mg of fluconazole daily for 14 days; 30 patients were selected to receive amphotericin lozenges and cream for 28 days. Clinical response rates were similar in both treatment groups throughout the study. The best mycologic response was noted after 1 week whereas the best clinical response was observed after 4 weeks. Clinical evidence of relapse and recurrence at 12 weeks was a common finding irrespective of treatment. Side effects were uncommon in both groups. PMID- 8351119 TI - Old age in health and disease. Lessons from the oral cavity. AB - It is not clear if aging distinctions can be made at the level of an organ or organism. The purpose of this study was to determine if a general definition of systemic aging, primary aging (influence of the passage of time), versus secondary aging (influence of extrinsic factors), can be used to discriminate the functional status of an individual organ system, the oral cavity. Thirty healthy, nonmedicated subjects (that is, those who exhibit primary aging) and 42 persons being treated for medical problems and taking prescription medications (that is, those who exhibit secondary aging), aged 75 to 96 years, from the oral physiology component of the Baltimore Longitudinal Study of Aging were evaluated. A standardized examination assessed gingival, periodontal, dental, and oral mucosal tissues. There were few substantive differences in oral health and function between primary and secondary aging subjects. Thus use of broad definitions of aging in an organism did not lead to meaningful predictions of the health or function of an individual organ system. Furthermore, the similarity in the oral condition between both groups studied here suggests substantial resiliency of the oral cavity during aging. PMID- 8351120 TI - Assessment of the need for treatment of postendodontic asymptomatic periapical radiolucencies in bone marrow transplant recipients. AB - Oral screening and treatment of existing oral disease before bone marrow transplantation have been reported to decrease the incidence of infectious complications during bone marrow transplantation. Information about the adverse sequelae of specific preexisting oral diseases during bone marrow transplantation is lacking. The presence of postendodontic periapical radiolucencies may suggest recurrent or latent infection. The purpose of this study was to compare the effect of endodontic treatment with nontreatment of asymptomatic postendodontic periapical radiolucencies on the frequency of infectious oral complications during bone marrow transplantation. The records of 276 patients undergoing bone marrow transplantation examined between July 1988 and June 1991 were reviewed retrospectively. Twenty-three postendodontic periapical radiolucencies were identified in 8 women and 15 men. The mean age of patients was 41 years (range, 25 to 58 years). Fourteen of the lesions were untreated, and nine were treated before bone marrow transplantation. When outcomes of transplant complications were compared, neither increased systemic infection as measured by neutropenic days febrile nor local oral infectious complications were significantly different. These results suggest that nontreatment of asymptomatic postendodontic periapical radiolucencies does not increase the incidence of infectious complications during bone marrow transplantation. PMID- 8351121 TI - Gingival Kaposi's sarcoma and periodontitis. A case report and suggested treatment approach to the combined lesions. AB - Kaposi's sarcoma is frequently observed in patients with the acquired immunodeficiency syndrome, and the mouth is a common site for these lesions. Gingival Kaposi's sarcoma lesions can often be exacerbated by coexisting periodontal disease. To obtain the best treatment results, it is important to recognize and treat the gingival Kaposi's sarcoma lesion and the associated periodontitis concomitantly. In this report we describe a case of oral Kaposi's sarcoma in which gingival debridement, root planning and scaling, and monitored oral hygiene were used in conjunction with intralesional and systemic chemotherapy. These combined therapies significantly reduced the size of the lesions and dramatically improved the symptoms. PMID- 8351122 TI - Oral T-cell lymphoma associated with celiac sprue. A case report. AB - Celiac sprue, also called nontropical sprue, is a malabsorption syndrome with symptoms that are triggered mainly by gluten ingestion. Non-Hodgkin's lymphoma of the gastrointestinal tract has been reported in patients with a long history of celiac sprue. This case report describes the occurrence of primary oral lymphoma in such a patient. This case is unusual because lymphomas associated with celiac sprue usually develop in the small intestine or in the stomach, and primary lymphoma in the mouth is itself uncommon. PMID- 8351123 TI - Oral melanotic macules. A review of 353 cases. AB - Clinical and histopathologic data were obtained on 353 cases of oral melanotic macules. The mean age at the time of diagnosis for all sites was 43.1 years. A significant predilection for females (p < 0.001) was noted and the most common location was the lower lip (33.0%). The mean size of the lesions was 6.8 mm. Brown was the most common color (64.9%), and most (66.0%) of the lesions were described as flat. Melanin was evident in both the basal cell layer and lamina propria in 93.5% of the cases. PMID- 8351124 TI - Rigid fixation of mandibular condyle fractures. AB - This article reviews the anatomy and surgical approaches for treating fractures of the mandibular condyle with plate and screw fixation. Advantages and disadvantages of the preauricular, submandibular, intraoral, retromandibular, and rhytidectomy approaches are presented. PMID- 8351125 TI - Primary alveolar soft part sarcoma of the tongue of an elderly man. A case report and review of the literature. AB - A 64-year-old black man had a primary alveolar soft part sarcoma of the tongue. It is unusual for this rare tumor to develop in this site in the elderly age group. The patient survived nearly 3 years with disease. When the patient expired, a complete autopsy was performed. The biopsy material of the primary tumor showed characteristic light microscopic appearance, intracellular periodic acid-Schiff positive inclusions after diastase reaction, and electron microscopic presence of crystals. Immunohistochemistry for neuron-specific enolase was positive. The autopsy confirmed widespread visceral and lymphatic metastases. The atypical features of this case, including the site of the primary lesion, age of the patient at diagnosis, immunohistochemistry of the tumor, and natural history of this neoplasm, suggest that alveolar soft part sarcoma may behave differently when arising in an extraskeletal site, and could possibly have a different histogenesis from the typical alveolar soft part sarcoma found in a younger population. PMID- 8351126 TI - Diagnosis and treatment of subpontic osseous hyperplasia. Report of a case. AB - This report describes a case of subpontic osseous hyperplasia that occurred in the posterior mandible of a healthy 67-year-old woman. The two hard masses, which were removed from beneath a fixed partial denture that was placed 35 years ago and spanned the lower left first premolar and the first and second molars, consisted of normal viable dense cortical bone. Only 30 cases of this phenomenon defined as a slow-growing, benign osseous proliferation occurring on the crest of the alveolar ridge beneath the pontic of a fixed partial denture have been described in the literature. Possible causes, including genetic programming, functional stimulus, and mild chronic irritation are discussed, as well as rationale for treatment of this anomaly. PMID- 8351127 TI - Clear cell odontogenic carcinoma with lymph node metastasis. AB - Clear cell odontogenic tumors are rare. Review of the literature showed 9 cases with a prominent clear cell component. These lesions have exhibited an aggressive behavior characterized by an infiltrative local growth pattern, recurrence, or metastases. We report a case of an odontogenic tumor that exhibited a biphasic pattern and was characterized by lymph node involvement identical histologically to the primary tumor. We conclude that the presence of a clear cell component in an ameloblastomatous tumor should be viewed as a sign of de-differentiation, and that a malignancy with or without metastases should be considered and ruled out in such cases. PMID- 8351128 TI - In vitro study of the penetration of three bacterial strains into root dentine. AB - The purpose of this study was to assess in vitro migration of the following three bacterial species into dentinal tubules: Streptococcus sanguis, Actinomyces naeslundii and Prevotella intermedia. Twenty-seven bovine incisors were randomly divided into three groups. Only the root dentin was used for the experiment. Within each group, the nine incisors were sectioned into 36 dentin blocks that were incubated with one of the tested bacterial suspensions. Twelve samples were taken after 10, 20, and 28 days. Half the samples were observed with scanning electron microscopy and the others with light microscopy after standard histologic procedures, and the depth of bacterial penetration was measured. Analysis of the examinations showed that whatever the technique used, only one strain on this experimental model migrated into dentinal tubules. S. sanguis was observed at a depth of 792 microns, but no migration was observed for either A.naeslundii or P.intermedia. The differences in migration of the bacteria tested appear to be related to their morphologic factors and cellular arrangement. PMID- 8351129 TI - [Spontaneous abortion and genetic natural selection]. AB - Author reviews the recent researches related to the genetic causes of spontaneous abortions as well as the results of the cytogenetic examinations of gametes, early embryos and clinical miscarriages. In the background of more than half of first trimester spontaneous pregnancy losses severe chromosomal aberration of the fetus can be found. About 60% of abnormal karyotypes is formed by autosomal trisomies, the rest is divided among polyploidies, X-monosomy and different structural anomalies. The incidence of fetal trisomies correlates with maternal age, besides balanced translocations of parents and delayed fertilisation can also play a role in the etiology of fetal chromosomal abnormalities. Regarding that most of these abnormalities accidentally develop because of meiotic or mitotic error there is no great risk of recurrence. Women who have had one spontaneous abortion will soon get pregnant again and give birth to a healthy child. The abortion of fetuses with abnormal karyotype is the appearance of natural genetic selection. PMID- 8351130 TI - [Surgical management of liver echinococcosis]. AB - In the last ten years 62 patients were operated on by the authors because of liver echinococcosis. Each of the infections caused by echinococcus granulosus. In the course of the examination ultrasonography, abdominal X-ray, Casoni test and ELISA were used. Angiography and ERCP were applied only to answer special questions. The echinococcus cysts were removed in 15 cases by atypical liver resection, in 42 cases by pericystectomy and in 5 cases by partial cystectomy using the Pringle's manoeuvre in all of them. Operative mortality was 3.22%. Jaundice was observed in three cases, fever in five cases, wound infection in two cases. Reoperations had to be performed in two cases. All of the patients were treated postoperatively with mebendasol (Vermox). Recurrence of the infection could not be observed. PMID- 8351131 TI - [First experience with the use of granulocyte-macrophage colony stimulating factor in pediatric oncology]. AB - Authors report their first experiences with the application of granulocyte macrophage colony stimulating factor in 12 pediatric cancer patients (14 cases). The drug was given in a 5 micrograms/kg single daily dose subcutaneously. Patients were divided into three main indication groups: 1. Severe neutropenia (white blood cell count < 1.0 G/l) and sepsis (6 patients); 2. Prolonged neutropenia (white blood cell count: 1.0-2.0 G/l) and delay in treatment (3 patients); 3. Dose-escalation of chemotherapy in therapy-resistant cases (4 patients). Authors report that in all cases a substantial raise in white blood cell count could be achieved after 5-6 days of granulocyte-macrophage colony stimulating factor treatment. No side effects were detected except of a moderate local pain at the site of the injection. Authors suggest that in the above described dose and way of administration granulocyte-macrophage colony stimulating factor can be an effective agent in the treatment of chemotherapy induced neutropenia in paediatric oncology. PMID- 8351132 TI - [Dual-chamber rate responsive cardiac pacing]. AB - The authors describe in this report their first experience with the implantation of a rate responsive, dual chamber pacemaker. They emphasize the advantages of this type of pacemakers: the maintenance of AV-synchrony and the rate increase in response to exercise. Meanwhile they call attention on the complexity of the ECG interpretation. PMID- 8351133 TI - [Massive colorectal hemorrhage in adult Schonlein-Henoch purpura]. AB - Schonlein-Henoch purpura is a well known syndrome, rare in adults, and is seldom accompanied with extensive colorectal haemorrhage. In abdominal purpura, the small bowel is more frequently involved, but cases of oesophageal, gastroduodenal and colorectal localisation also have been reported. The cases with colorectal bleeding, appearing in adulthood and elderly patients, could cause differential diagnostic problems. Described endoscopic features of one patient, who was referred to our department, because of colorectal bleeding. The treatment, course of disease and endoscopic follow-up is presented. No previous endoscopic documentation of this type of localisation has been reported in Hungarian literature, so far. PMID- 8351135 TI - [Disposal of medical refuse by burning. Procedures and possibilities]. PMID- 8351134 TI - [Position of the management of the ETT (Scientific Council on Health) on the esterin campaign]. PMID- 8351136 TI - [AUDIT--control of the quality of surgery in Great Britain]. PMID- 8351137 TI - [Significance of varicella zoster infection in pregnancy and labor]. AB - The authors observed 25 pregnant or delivering women with varicella and their offsprings from 1986 to 1991. The course of varicella of the pregnant and delivering mothers was generally benign, only one progressive case was observed with pneumonitis after delivery; this woman also recovered upon acyclovir treatment. All but one woman delivered on term, in one case the varicella developed on the 27th gestational week; this woman gave birth to a premature baby of 1180 g who died from a cerebral and lung hemorrhage. No sign of varicella zoster virus infection was found at the autopsy. No congenital varicella syndrome was observed during the investigation period. Varicella-zoster immunoglobulin was given to 21 newborn babies, immediately after birth. Eight of the newborns developed varicella, the course of the disease was mild in seven cases. One baby who was given no varicella-zoster immunoglobulin and developed progressive varicella recovered after acyclovir therapy. During the investigation period the authors observed three cases of zoster in infants whose mothers had had varicella during pregnancy. The authors discuss the possibilities of prevention of varicella-zoster virus infection of newborns and infants. PMID- 8351138 TI - [The importance of capnometry and pulse oximetry in laparoscopic cholecystectomy]. AB - Recently the number of surgical and gynaecological operations performed via laparoscope has increased. The authors looked for the answer whether the carbon dioxide insufflated into the abdominal cavity during laparoscopy could cause significant change in the amount of carbon dioxide expired per minute. They measured the concentrations of carbon dioxide at the end of expiration, the amount of carbon dioxide produced per minute and the oxygen saturation during ataranaesthesia, muscle relaxation, intratracheal intubation and controlled mechanical ventilation in 20 cases of laparoscopic cholecystectomy. According to the results the amount of carbon dioxide exhaled per minute increased 1-3 minutes after insufflation and its maximum value was reached within 15-30 minutes (120 140% of the basic value). The continuous pulsoxymetrical examination showed that the constant intraperitoneal pressure equal or higher than 13-15 Hgmm could lead to the increase of the intrapulmonal shunt-circulation due to dystelectasis of the pulmonary bases. This could be prevented by increasing the respiratory pause pressure to the level corresponding to the intraperitoneal pressure. In order to decrease the intraoperative anaesthesiological risks associated with the procedure the authors propose the use of capnometer and pulsoxymeter for the mentioned operation; this will keep level up with the relatively small risks associated with the postoperative period of the laparoscopic operations. PMID- 8351139 TI - [Leukocyte adhesion defect--a rare form of congenital immune deficiency]. AB - Leukocyte adhesion defect (LAD) is an inherited defect of phagocytic function. This disorder is characterised by delayed separation of the umbilical cord, severe recurrent bacterial infections, impaired formation of pus, and high leukocyte counts. The granulocytes have severe defect in their chemotactic mobility and endocytosis. The disease is attributed to the absence of the leukocyte adhesion molecules. (CD11/CD18), which can be verified with monoclonal antibodies. The authors describe the disease-process of the first patient diagnosed in Hungary. Perinatally the omphalitis, periumbilical abscess and periproctal abscess leading to rectovaginal fistula, in the first months the otitis, mastoiditis, and expressed leukocytosis referred to the impaired function of phagocytic cells, which was verified by laboratory tests as well. The decreased inflammation and cicatrization were also striking. This severe form of LAD can be cured only by bone marrow transplantation with preliminary sanitation of the foci of infection. It took about six months. Unfortunately, the patient died of sepsis immediately before transplantation. PMID- 8351141 TI - [The activities of Jozsef Lenhossek as museologist and anatomist]. PMID- 8351140 TI - [Antioxidant effect of vitamin E in experimental hyperlipidemia]. AB - The effect of Vitamin E treatment was studied in experimental hyperlipidaemia. The male Wistar rats got control diet and parallel fat rich diet contained 2% cholesterol, 0.5% cholic acid and 20% sunflower oil added into LATI food during 9 days. The treated hyperlipidemic animals got vitamin E for 9 days in daily 8.56 mg/b.w.kg dose mixed in food. The effect of antioxidant treatment on changes of lipid peroxidation, content of diene conjugates, thiobarbituric acid reactive products and natural scavenger capacity of rat liver homogenates and microsome fractions were measured by spectrophotometric and luminometric methods. Fatty acid composition of lipid fraction of samples was determined by capillary gas chromatography. Vitamin E in hyperlipidemia increased the natural scavenger capacity of liver and decreased the level of thiobarbituric acid reactive products and dien conjugates. There was no change in fatty acid composition of samples on effect of vitamin E antioxidant treatment. PMID- 8351143 TI - [Licensing rules on private medical practice]. PMID- 8351142 TI - [Aladar Petz, M. D. (1888-1956), world famous surgeon and inventor from the city of Gyor]. PMID- 8351144 TI - [Halothane hepatitis]. AB - The greatest disadvantage of the halothane, widely used in the anaesthesiology is its ability to cause liver damage. After halothane anaesthesia mild liver enzyme elevation in the one fifth of the patients was detected. The incidence of fatal halothane hepatitis is rare. It depends on several risk factors: on the genetic predisposition, repeated halothane anaesthetics, female sex, age of patient, obesity, intrahepatic hypoxia and enzyme induction. In the pathophysiology of liver toxicity the metabolism of halothane and immune functions play an important role. In this review the last results of researches concerning to the hepatotoxicity of halothane are summarised and the authors call the attention on the opportunity of its effective prevention. PMID- 8351145 TI - [Correlation between tumor regression and survival time after chemotherapy in cancer of the oral cavity]. AB - The examinations were performed on thirty patients with biopsy-confirmed squamous cell carcinoma of the oral cavity in clinical stage T2-3No-2M0. The aim of the present study was to perform a histological evaluation of the effect of preoperative intra-arterial treatment of surgically removed tumours and to analyse the correlations with the survival of the patients. The tumour regression (R) was evaluated quantitatively on a scale ranging between 1 and 4 points. The evaluation yielded a value of R1 in 8/30 cases (residual tumour was not found histologically). A tumour of microscopic size (R2) was found in 5/30 cases. Partial regression (R3) was established in 12/30 cases, and a slight response (R4) in 5/30 patients. The histologic picture was evaluated qualitatively on the basis of three arbitrarily chosen parameters. Examinations were made on the morphological picture of the residual cancer (C), the inflammatory reaction of the stroma (S) and the demarcation tendency of the tumour (D) and the sum of these values (A). The higher this point score, the poorer the tumour in question responds. Tumours with a score of A3-5 proved to have a very favourable prognosis in contrast with those with a score of A8-9. For the borderline scores of A6-7 the subsequent fate of the patient was decided by the extent of the original tumour and by the occurrence or not metastases. It is noteworthy that, with a comparatively small number of patients, a significant correlation was demonstrated between the survival and the total qualitative point count (A), the S value and the D value. PMID- 8351147 TI - [Possibilities and limitations of minimally invasive methods in thoracic surgery]. AB - First experiences with minimal invasive thoracic surgery are presented. Between November 1991 and September 1992 37 intrathoracic operations--3 lobectomies among them--have been performed by their modified method. A special surgical thoracoscope was inserted through a 6-7 cm-s incision into the thorax. This instrument provides a direct view with excellent distal illumination and it also can be applied by video-thoracoscopic system. It is emphasized that their method needs further development. It's practical value and result depend on the appropriate consideration of possibilities and limits, and on careful selection of the patients. PMID- 8351146 TI - [Immunohistochemical study of hepatitis B surface and core antigens in HBsAg seronegative and seropositive organ and tissue donors]. AB - Hepatitis B virus antigen screening in the liver of organ and tissue donors was performed. The results of a 4-year period are compared with the serological findings. The immunohistochemical and serological data altered in two out of 15 organ donors. HBV antigen could be detected in the liver, however the serological examination was negative in these persons. The author emphasize the risk of a possible hepatitis B virus transmission through organ and tissue transplantation. A detailed examination of the donors is suggested. PMID- 8351148 TI - [Genetic counseling and successful pregnancy in patient with Wilson disease]. AB - The principles of genetic counselling are summarized in a female with Wilson's disease. Pregnancy after appropriate treatment during gestation had a successful outcome: a healthy boy. PMID- 8351151 TI - [Sr. Philomena Schmidt: "I want to be the mouthpiece for basics!". Interview by Harald Verworner]. PMID- 8351149 TI - [He who wants to learn to die, first must learn to live]. PMID- 8351150 TI - [Care and stay healthy]. PMID- 8351152 TI - [Reading behavior and leasure time]. PMID- 8351153 TI - George Washington Crile, anoci-association, and pre-emptive analgesia. PMID- 8351154 TI - The tail-flick and formalin tests in rodents: changes in skin temperature as a confounding factor. AB - In the tail-flick test as well as in the late phase in the formalin test skin temperature may in an important way influence the response. A reduced skin temperature may be misinterpreted as analgesia, and an increased skin temperature as hyperalgesia. These effects and the mechanisms that cause them are discussed. It is of particular importance to be aware of these confounding factors when using drugs or making lesions that influence blood flow or temperature regulation. It is important that all variables influencing the test results are kept constant throughout the experiment. This includes not only the ambient temperature, but also factors that may influence the vasomotor tone of the animals. PMID- 8351155 TI - Sex differences in responsiveness to painful and non-painful stimuli are dependent upon the stimulation method. AB - Sex differences in thermo- and electrocutaneous responsiveness to painful and non painful stimuli were investigated in 20 women and 20 men. Heat pain, warmth, and cold thresholds were assessed on the hand and foot with a Peltier thermode system. In addition, subjects used magnitude estimation to judge the sensation intensity evoked by temperatures ranging from 38 degrees C to 48 degrees C applied to the forearm. To measure detection, pain, and tolerance thresholds of electrocutaneous sensitivity, electrical pulses were administered to the hand. Magnitude estimates of sensation intensity were assessed for stimuli ranging from 0.5 mA to 4.0 mA. There were no sex differences in heat pain, warmth and cold thresholds. There were significant sex differences in electrical detection, pain and tolerance thresholds, with lower thresholds in women. Correspondingly, magnitude estimates were similar in women and men when using thermal stimuli while women judged stimuli from 2.5 mA on as more intense than men when using electrical stimuli. Despite these discrepancies, the measures for pain responsiveness from the two stimulation methods correlated significantly. In contrast, no significant correlations between the methods were found when considering the responsiveness to non-painful stimuli. The findings help to clarify controversies in the pain literature about sex differences. Results affirming and denying such differences could be obtained within a single sample, with stimulation method as the critical variable. PMID- 8351156 TI - A clinical and experimental investigation of the effects of tizanidine in trigeminal neuralgia. AB - Experiments in cats anesthetized with alpha-chloralose showed that tizanidine (TZD: 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiodiazole) partly resembled carbamazepine (CBZ) and baclofen (BCF) in that it depressed excitatory transmission and facilitated segmental inhibition of neurons in the spinal trigeminal nucleus oralis which responded to tapping but did not affect the response of neurons which responded to light stroking of the skin or bending the whiskers. In a double-blind crossover study of TZD in refractory trigeminal neuralgia, 8 of 10 patients had fewer painful paroxysms while on TZD. However, the 6 patients who elected to continue taking TZD experienced a recurrence of their attacks of trigeminal neuralgia within 1-3 months. The limited efficacy of TZD in the treatment of trigeminal neuralgia may be related to the fact that it has no effect on neuronal responses to low-threshold mechanoceptive stimuli, suggesting that low-threshold mechanoceptive neurons play an important role in the pathogenesis of trigeminal neuralgia. PMID- 8351157 TI - Temporal factors in the enhancement of morphine analgesia by desipramine. AB - Administration of desipramine, the tricyclic noradrenergic agent, for 7 days pre operatively, had been found to potentiate postoperative morphine analgesia. In this study we investigated the necessary timing of administration of desipramine in its action to potentiate morphine analgesia. We report that the administration of desipramine for only 3 days, starting 7 days before surgery, also potentiated postoperative morphine analgesia and that the analgesia observed was not different from that in patients receiving a full 7 days of desipramine pre operatively. The potentiation of morphine analgesia observed was most evident as a prolongation of the analgesic response. Patients who also received desipramine for only 3 days, but starting 3 days pre-operatively had an analgesic response to postoperative morphine that was the same as that in patients receiving placebo. The ability of the administration of desipramine early in the pre-operative week to interact with postoperative morphine and the lack of response when desipramine was given late in the week does not have an explanation at present. However, it may reflect the known latency in humans to the onset of the central effects of tricyclic antidepressants (TCAs). PMID- 8351158 TI - Magnesium sulphate injected subcutaneously suppresses autotomy in peripherally deafferented rats. AB - In rats, recent evidence suggests that injury discharge caused by peripheral nerve section releases excitatory amino acids into the spinal cord which in turn influences decisively the development of autotomy, a self-mutilation behaviour directed towards the denervated areas. Autotomy has been proposed as a behavioural correlate of the neuropathic pain which occurs in humans after complete nerve lesions. Mg2+ ions have been shown to offer protection from neurological and degenerative disorders in which excitatory amino acids are putatively involved. To ascertain the preventive value of Mg2+ administration on autotomy, male rats underwent unilateral ligation and transection of the sciatic and saphenous nerves 30 min after being injected subcutaneously (s.c.) with 300 or 600 mg/kg MgSO4 or saline. Thereafter, autotomy was monitored for 8 weeks. Serum, lumbosacral (L1-S1) and brain magnesium levels were analyzed 0, 30, 60, 120, 180, 240, 360 min and 24 h after the s.c. injection of 600 mg/kg MgSO4. Serum magnesium levels increased quickly from 1.02 mM (0 time) to 4.52 mM (at 60 min) and dropped afterwards to reach physiological levels at 6 h. Peak increments in L1-S1 and brain Mg2+ levels were smaller (32% and 30%, respectively) although maintained for at least 6 h. Magnesium pretreatment in a significant and dose dependent manner (1) largely suppressed autotomy, (2) decreased final autotomy scores, (3) delayed autotomy onset, and (4) decreased the percentage of animals engaged in high autotomy behaviors. The data support a role for excitatory amino acids in determining susceptibility to autotomy and suggest a hopeful way to prevent neuropathic pain in humans after peripheral deafferentation. PMID- 8351159 TI - The roles of spatial recruitment and discharge frequency in spinal cord coding of pain: a combined electrophysiological and imaging investigation. AB - An investigation was conducted to examine both temporal and spatial factors likely to be involved in spinal cord nociceptive coding by wide cord nociceptive neurons. Three separate methodologies were employed. First, the impulse frequency responses of L4 spinal cord wide-dynamic-range (WDR) neurons to gentle mechanical stimulation, vigorous but innocuous brushing, warmth (43 degrees C), and nociceptive thermal stimuli (45-49 degrees C) were electrophysiologically characterized in unanesthetized, spinal cord-transected rats. Second, the spatial distribution of evoked activity in response to the same types of mechanical and thermal stimuli was examined utilizing the 14C-2-deoxyglucose (2-DG) metabolic mapping method in the same type of animal preparation. Finally, the contributions of impulse frequency and numbers of neurons activated to encoding the distinction between painful and non-painful sensations were directly evaluated by electrically stimulating axons within the spinal cord anterolateral quadrant (ALQ) of conscious human subjects. Electrophysiological findings revealed that vigorous but innocuous brushing produced intermediate rates of impulse discharge significantly greater than those produced by 35 and 43 degrees C stimuli, yet indistinguishable from those produced by relatively low nociceptive temperatures (45-47 degrees C). Thus, the discharge frequencies of individual dorsal horn WDR neurons alone do not provide sufficient information to encode the distinction between innocuous and low intensity nociceptive stimuli. Mapping of spinal cord activity by the 2-DG method revealed that nociceptive stimuli activated extensive rostro-caudal regions extending from L1-L5. In contrast, vigorous but innocuous brushing evoked metabolic activity that was confined to a narrow zone within L3. Thus, as predicted from previous studies, the distinction between nociceptive and non-nociceptive sensory events may be encoded, in part, by differences in the spatial distribution, and hence, the relative numbers of spinal cord neurons activated by nociceptive and innocuous stimuli. The responses of conscious human subjects to varying frequencies and intensities of electrical ALQ stimulation clarify the significance of the large numbers of spinal cord neurons activated by nociceptive stimuli. With stimulus frequency held constant at 50 Hz, low stimulus currents, sufficient to activate only small numbers of ALQ axons, produced innocuous sensations. Higher stimulus currents, sufficient to activate larger numbers of neurons, consistently produced painful sensations. Increasing ALQ stimulus frequency at currents subthreshold for pain or increasing stimulus currents at frequencies subthreshold for pain resulted in painful sensations, thus indicating that both discharge frequency and numbers of neurons activated are both important factors in the encoding of pain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8351160 TI - Chronic effects of topical application of capsaicin to the sciatic nerve on responses of primate spinothalamic neurons. AB - The responses of 144 spinothalamic tract (STT) cells were recorded in 15 anesthetized macaque monkeys (Macaca fascicularis). Three to 4 weeks prior to the acute experiment, the sciatic nerve was surgically exposed on one or both sides so that capsaicin or vehicle could be applied. Responses of STT cells recorded in 3 experimental groups were compared: untreated (21 cells), vehicle-treated (40 cells), and capsaicin-treated (83 cells). The background activity of cells in the vehicle- and capsaicin-treated groups was the same as in the untreated group (that is, cells on the side contralateral to surgery). Responses to innocuous (BRUSH) and noxious (PINCH) mechanical stimuli were unchanged by vehicle or by capsaicin treatment. However, responses to other noxious (PRESSURE and SQUEEZE) mechanical stimuli were significantly increased in the vehicle-treated group. Compared with a large reference population, all experimental groups showed a significant increase in overall responsiveness to mechanical stimuli (as determined by cluster analysis), greatest in the vehicle-treated group. Responses to noxious heat stimuli were significantly reduced in the capsaicin-treated group for 45 degrees C and 47 degrees C stimuli. Volleys in A fibers, probably A delta fibers, evoked prolonged responses in many STT cells of all treatment groups. Electron microscopic counts of axons in the sciatic nerves of animals treated with capsaicin showed a reduced number of C fibers but no appreciable loss of myelinated axons. This loss of unmyelinated sensory fibers was presumably responsible for the reduction in the responses of the STT cells to noxious heat stimuli. Increased responses to some noxious mechanical stimuli and to A fiber volleys may have been the consequence of several factors, including surgical manipulation, a chemical action of vehicle and a contralateral action of capsaicin treatment. PMID- 8351161 TI - The sensory response to capsaicin during repeated topical exposures: differential effects on sensations of itching and pungency. AB - Changes in sensory irritation were measured during repeated topical exposures to capsaicin over 2 days. The perceived intensities of itching and pungent sensations, predominantly burning and stinging/pricking, were assessed every 60 sec during 5 applications of capsaicin at inter-stimulus intervals (ISI) of 90 min (Exp. 1) or 15 min (Exp. 2) and in follow-up tests 24 h later. Psychophysical measurements were obtained with a hand-held dynamometer in conjunction with the method of magnitude production. When the ISI was 90 min, itching and pungency were both significantly reduced (i.e., desensitization occurred) by the fifth exposure; however, the reduction occurred more rapidly and dramatically for itching. After 24 h, desensitization remained significant only for itching. When the ISI was 15 min, the sensations on day 1 first intensified in a manner consistent with sensitization, then declined in a manner consistent with desensitization; compared to pungency, itch exhibited less sensitization and more desensitization. On day 2, overall intensity was less for both categories of sensation, primarily because of a reduction in sensitization. Marked individual differences were observed in the overall sensitivity to capsaicin, the time course of sensation, the susceptibility to capsaicin-induced itch, and the rate and duration of sensitization and desensitization. The results are discussed in terms of current hypotheses about the sensory mechanisms that underlie chemically induced itch and the use of capsaicin as a topical analgesic and antipruritic. PMID- 8351163 TI - Enhancement of the epidural morphine-induced analgesia by systemic nifedipine. AB - We evaluated postoperative pain relief and incidence of side effects of the combination of epidural morphine (0.5 mg) and sublingual nifedipine (10 mg). Thirty-six patients were submitted to elective operations and divided into 4 groups receiving placebo (groups A and B) or morphine (groups C and D) by the epidural route, followed by sublingual placebo (groups A and C) or nifedipine (groups B and D) administered in a double-blind fashion. The mean (+/- S.E.M.) periods of analgesia were 16.6 +/- 1.6 (A), 15 (B) 105 +/- 77.0 (C), and 428.8 +/ 72.0 (D) min. No patient had pruritus, excessive sedation or respiratory depression. Episodes of nausea and/or vomiting requiring no specific therapy were observed in groups A, B and D. Nifedipine-treated groups also had a significant fall in blood pressure which was controlled by rehydration. These results indicate that epidural morphine-induced postoperative pain relief may be enhanced by systemic administration of nifedipine, with easily controlled side effects. PMID- 8351162 TI - Are poor metabolisers of sparteine/debrisoquine less pain tolerant than extensive metabolisers? AB - It has recently been shown that O-demethylation of the opioid drug codeine to morphine depends on the sparteine/debrisoquine oxygenase (CYP2D6) which in man exhibits genetic polymorphism. Morphine may be an endogenously formed substance in mammalians. Therefore, it may be hypothesized that the final step in an endogenous synthesis of morphine from codeine also depends on CYP2D6. CYP2D6, which is present in the liver and presumably also in the brain, is not expressed in subjects who are poor metabolisers of the sparteine/debrisoquine type. We have determined sensitivity to painful stimuli in 94 extensive metabolisers and 82 poor metabolisers of sparteine in 2 phasic (pain thresholds to heat and pressure) and 1 tonic (cold pressor test) experimental pain model. Extensive and poor metabolisers did not differ significantly in the 2 phasic pain models neither with respect to pain detection nor pain tolerance thresholds. However, for the cold pressor test, peak pain ratings and area under the pain rating-time curve during 2 min were significantly higher in poor than in extensive metabolisers (P = 0.0024 and 0.044). Furthermore, a substantially higher fraction of poor metabolisers prematurely withdrew their hand from the ice water during the cold pressor test due to intolerable pain (32 vs. 18%, P = 0.0545). We conclude that poor metabolisers of sparteine may be less tolerant to tonic pain than extensive metabolisers, and we hypothesize that this may be related to an inherited defect in endogenous synthesis of morphine via CYP2D6 in the brain. PMID- 8351164 TI - Pain assessment with interactive computer animation. AB - A method of assessing pain using interactive computer animation is described. This method provides quantitative measurements of different qualitative aspects of pain experience without reliance on fine verbal distinctions. A clinical comparison of this procedure and the Short-Form McGill Pain Questionnaire (SF MPQ) is reported. Correlations between paper and animated visual analogue scales (VAS) showed that animated measurements can be reliably compared to traditional paper-based reporting. Measurements using animations designed to assess different qualities of pain experience correlated significantly with SF-MPQ measures, providing good concurrent validity. A difference was found between patients who chose only one quality-of-pain animation and those who chose more than one, possibly indicating a difference in patients' verbal fluency. Patients overwhelmingly preferred the interactive animations to the paper-based method. PMID- 8351165 TI - Analysis of variance in the study of drug interactions. PMID- 8351166 TI - The effect of CPP in neurogenic pain: inhibition of spinal or cortical NMDA receptors? PMID- 8351167 TI - Is intrathecal octreotide analgesic or what? PMID- 8351168 TI - Stress riser fractures of the hip after sliding screw plate fixation. PMID- 8351169 TI - Do no harm? PMID- 8351170 TI - The basic science of anterior cruciate ligament surgery. AB - Surgery for ligamentous injuries of the knee continues to be one of the most common procedures performed by orthopaedists. Anterior cruciate ligament (ACL) reconstructions are addressed specifically. Basic science and laboratory research have had a dramatic effect on our understanding of the underlying pathology of the injury, and this information has been used in the development of the clinical procedures most commonly used today. The classic stages of ligament healing are contrasted with the limited potential of the ACL. Surgical options using autografts, allografts, augmentation devices, and primary repair are discussed. Present research is examined for possible future directions in the treatment of ligament injuries. PMID- 8351171 TI - The basic science of meniscus repair. AB - The meniscus transmits load and reduces stress and compression of the articular cartilage and subchondral bone of the knee during weight bearing. Removal of even small portions of the meniscus may increase joint contact forces dramatically and lead to early degenerative changes in the knee. The goal of meniscus surgery is to preserve as much functional meniscus tissue as possible in the hope of decreasing the risk of late degenerative sequelae and still relieve the symptoms associated with the tear. The indication for repair of any meniscus tear should depend solely on the ability to technically stabilize and coaptate the tear. This article reviews the basic treatment principles of meniscal tears. PMID- 8351173 TI - Complications associated with the Seidel nail. AB - The Seidel nail is an intramedullary locking device available for the treatment of humeral shaft fractures that require operative fixation. A retrospective review of 13 consecutive patients treated with the Seidel nail was undertaken to evaluate results, with attention to complications. No nerve palsies or infections occurred. Complications occurred in 46% of the patients and included intraoperative comminution associated with lateral placement of the pilot hole, instrumentation failure, and underreaming of the canal, resulting in iatrogenic fracture. PMID- 8351172 TI - Rush rods versus plate osteosyntheses for unstable ankle fractures in the elderly. AB - Fifty patients with unstable fibular fracture were randomized into two groups. Twenty-five were treated with Rush rods and 25 with AO plates. Eighty-eight percent of patients treated with intramedullary rods had good or fair functional results, compared with 76% of patients undergoing plate and screw fixation. Full weight bearing was possible 6 weeks earlier with Rush rods than with AO plates, and there was less morbidity in the intramedullary group than in the AO group. This study indicates that Rush rods are a useful tool in elderly patients with soft bone, who are at risk for complications with plate and screw fixation. PMID- 8351174 TI - Preoperative diagnosis of a forearm peripheral schwannoma. AB - A 34-year-old man had a right distal forearm mass of unknown etiology for 6 years. Magnetic resonance imaging showed a tumor in continuity with the median nerve. Fine-needle biopsy revealed it to be a schwannoma. Surgical excision was performed by separating the nerve fascicles from the tumor. The patient was asymptomatic at 12-month follow-up. PMID- 8351175 TI - Failure of a well-fixed bone-ingrown titanium hip prosthesis. AB - A cementless titanium femoral stem was revised 5 years after implantation because of acute pain and progressive osteolysis. Substantial amounts of titanium and polyethylene wear debris were found in the surrounding tissues. Multiple sources of this debris were found as well as detachment of titanium fiber-mesh pads from the body of the femoral stem. PMID- 8351176 TI - Disruption of the anterior cruciate ligament in a 4-year-old child. AB - Anterior cruciate ligament (ACL) injuries in children are rare. Thus, the natural history of ACL injuries in skeletally immature patients is unknown. This case represents the longest follow-up (11 years) reported in the literature of an ACL injury in a child of less than 5 years old. PMID- 8351177 TI - Failure of the polyethylene liner leading to notching of the femoral component in bipolar prostheses. AB - Polyethylene wear is an increasingly recognized problem in joint replacement surgery. Three cases of polyethylene wear in bipolar hip prostheses are presented. Owing to failure of the polyethylene liner, impingement of the metal shell produced notching of the femoral component. PMID- 8351178 TI - A 54-year-old woman with a 15-year history of pain in both legs and back. PMID- 8351179 TI - Simple surgical techniques to protect the soft tissues during total knee arthroplasty. AB - The surgical techniques involved in total knee arthroplasty are often overshadowed by implant design, metallurgy, and fixation methods. This is especially true when considering the handling of the soft tissues rather than the bony cuts. The authors believe that protection of the soft-tissue structures around the knee is of paramount importance and describe six surgical techniques that they use to accomplish this during total knee arthroplasty. PMID- 8351180 TI - Properties of spatial representations: data from sighted and blind subjects. AB - Five questions concerning the properties of spatial representations are explored. (1) How accurately does a spatial representation correspond to the true scene? (2) If inaccurate, how does it differ? (3) Are representations of a familiar scene more accurate than those of an unfamiliar one? (4) Do representations of a scene currently in view differ from those retained in memory? (5) Do the representations of the blind have properties comparable to those of the sighted? Seven sighted and 7 highly mobile blind subjects, all familiar with a room, and 6 sighted subjects unfamiliar with it, were asked to estimate the absolute distances between 10 salient objects in the room. The 14 familiar subjects made their estimates twice: while they were in the room, and while they were remote from it. Regression analyses showed that the estimates of all subjects had strong metric properties, being linearly related to true distance, with a true zero point; and multidimensional scaling showed that all subjects produced distance estimates that could be scaled in two dimensions to closely match the actual locations of the objects. Familiarity had no effect. The effect of location of testing was the same for both the sighted and the blind: all subjects displayed better spatial knowledge when tested in the room; and all subjects underestimated true distance substantially when tested out of the room. The results showed no qualitative differences as a function of blindness, at least for these highly skilled blind travelers. PMID- 8351181 TI - Localization of electrocutaneous stimuli on the fingers and forearm: effects of electrode configuration and body axis. AB - Four experiments were done on the effects of electrode configuration (concentric vs. unifocal) and body axis (longitudinal vs. transverse) on localization of electrocutaneous pulse stimuli at the fingers and forearm. Subjects pointed to the apparent location of current pulses. For the transverse placement of electrodes, pulses were localized correctly, whatever the configuration and the body site might be. In addition, intrasubject variability at the forearm was smaller for the transverse axis than for the longitudinal axis. For the longitudinal placement of electrodes, pulses were localized as a function of configuration and body site. At the fingers, concentric electrodes provided precise localization but unifocal electrodes provided a great mislocalization; and intrasubject variability of localization was larger for the unifocal electrodes than for the concentric electrodes. At the forearm, whatever the configuration might be, the pulses were localized more proximally than the stimulus site; and intrasubject variability of localization did not differ between the configurations. These results are related to Boring's anchor theory, apparent distance between two points, and the localization of other somatosensory stimuli. PMID- 8351182 TI - When acoustic sequences are not perceptual sequences: the global perception of auditory patterns. AB - Warren, Bashford, and Gardner (1990) found that when sequences consisting of 10 40-msec steady-state vowels were presented in recycled format, minimal changes in order (interchanging the position of two adjacent phonemes) produced easily recognizable differences in verbal organization, even though the vowel durations were well below the threshold for identification of order. The present study was designed to determine if this ability to discriminate between different arrangements of components is limited to speech sounds subject to verbal organization, or if it reflects a more general auditory ability. In the first experiment, 10 40-msec sinusoidal tones were substituted for the vowels; it was found that the easy discrimination of minimal changes in order is not limited to speech sounds. A second experiment substituted 10 40-msec frozen noise segments for the vowels. The succession of noise segments formed a 400-msec frozen noise pattern that cannot be considered as a sequence of individual sounds, as can the succession of vowels or tones. Nevertheless, listeners again could discriminate between patterns differing only in the order of two adjacent 40-msec segments. These results, together with other evidence, indicate that it is not necessary for acoustic sequences of brief items (such as phonemes and tones) to be processed as perceptual sequences (that is, as a succession of discrete identifiable sounds) for different arrangements to be discriminated. Instead, component acoustic elements form distinctive "temporal compounds," which permit listeners to distinguish between different arrangements of portions of an acoustic pattern without the need for segmentation into an ordered series of component items.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351183 TI - Covert effects of alcohol revealed by event-related potentials. AB - Contradictory evidence as to the effects of alcohol on early information processing stages has been obtained from behavioral and psychophysiological investigations. In the present study, choice reaction times, error rates, and event-related potentials (ERPs) were recorded in a task in which variations in stimulus discriminability and of the (task irrelevant) correspondence between stimulus location and response location were orthogonally combined. Both discriminability and stimulus-response correspondence affected reaction time and electrophysiological chronometric measures as expected. However, no behavioral effects of alcohol were observed, possibly because of strategic adjustments. Psychophysiological chronometric measures indicated that alcohol leaves the initial flow of perceptual evidence to motor stages unimpaired, whereas it appears to increase the duration of stimulus evaluation. Interestingly, a number of alcohol effects appeared in the ERP amplitudes. Decrements in early ERP components indicate alcohol-induced impairments of involuntary visual attention and/or the automatic stimulus location-dependent activation of response channels. In contrast, a strong enhancement of a late slow-wave component under alcohol may reflect the investment of processing resources in order to maintain normal performance levels. PMID- 8351185 TI - A reexamination of duplex perception evoked by intensity differences. AB - Duplex perception is a term used to describe the simultaneous evocation of phonetic and nonphonetic percepts, a phenomenon held by some to reveal the operation of a specialized module for phonetic perception. In a widely cited experiment by Whalen and Liberman (1987), duplex percepts were created by replacing the third format transition in a synthetic syllable with a sinusoidal tone glide and manipulating the level of the glide relative to the rest of the syllable. We discuss this study, and report four experiments. The first two made a systematic estimate of the "duplexity threshold"--the tone glide level at which a chirp-like sound could be heard as well as the speech-like syllable. In the third and fourth experiments, we used the results of the first to repeat and extend the experimental procedures in the original Whalen and Liberman study. We discuss the differences in outcome, and conclude that our results may be explained without the need to invoke a specialized phonetic module. PMID- 8351184 TI - The gap between rod and frame influences the rod-and-frame effect with small and large inducing displays. AB - The role of the spatial separation between the ends of a rod and a frame's inner edge (gap) in modulating the rod-and-frame effect (RFE) has been studied here with frames subtending either large or small retinal angles. With a large frame, rod settings were always in the direction of frame tilt (direct effects) and varied inversely with gap size. With a small frame, rod settings were in the direction of frame tilt for tilts between 7.5 degrees and 15 degrees; with larger frame tilts, rod settings in the direction opposite that of the frame were observed (indirect effects). Increasing gap size produced a tendency toward negativity (away from frame tilt). Consequently, direct effects were larger for small gaps, while the opposite was true for indirect effects. Overall, these results point to the importance of gap size in modulating the RFE, for both large and small displays. PMID- 8351186 TI - Concurrent processes: the affect-cognition relationship within the context of the "mere exposure" phenomenon. AB - The affect-cognition relationship and Zajonc's (1968) "mere exposure" hypothesis were examined in two studies that involved ratings of: (1) preference and familiarity for geometric forms previously scaled for complexity and (2) preference or height and familiarity for male yearbook pictures previously scaled for attractiveness or height. Two exceptions to his hypothesis were noted: simple geometric forms and unattractive faces showed satiation, and faces seen once before were rated more attractive than both novel faces and faces seen twice before. Moreover, mere exposure effects were noted with a nonaffective dimension (height). The major finding was that presentation frequency generally manifested independent relations to affect and rated familiarity, as well as to height and rated familiarity, therefore evoking a concurrent response process (Eriksen, 1960). PMID- 8351187 TI - Tensorial basis to the constancy of perceived object extent over variations of dynamic touch. AB - Subjects wielded occluded rods, with or without attached masses, and reported the distances reachable with their distal tips. Experiments 1-3 compared wielding about the wrist, the elbow, and the shoulder. Experiments 4 and 5 compared free wielding, using the whole arm, with wielding only about the wrist. The two comparisons, respectively, were of spatial and temporal variations in the rod's rotational inertia. Perceived extent was found to be constant in both comparisons. This constancy was tied to the inertia tensor Iij defined about a point that remains a fixed distance from the object during wielding--an invariant of the spatially and temporally dependent patterning of mechanical energy impressed upon the tissues of the body. Discussion focused on the reciprocal action and perception capabilities of multisegmented limbs, the tensorial relations in the neurobiology of dynamic touch, and the strategy of understanding perceptual constancy through invariants. PMID- 8351188 TI - Revisitation of the luminance conditions for the occurrence of the achromatic neon color spreading illusion. AB - This paper develops the idea (Bressan, 1993) that neon spreading derives from the perceptual scissioning of ordinary assimilation color, a process identical to that occurring with nonillusory colors in phenomenal transparency. It is commonly held that the critical elements in achromatic neon spreading patterns must be of luminance intermediate between that of the embedding lines and of the background. The interpretation of neon spreading on the basis of color scissioning, however, predicts that neon spreading should also be observed for different luminance hierarchies, provided that these are compatible with transparency. This prediction found experimental support in the present work. The results suggest that (1) the widespread notion that chromatic and achromatic neon spreading must be mediated by separate mechanisms is unwarranted; (2) the widespread notion that color spreading in ordinary assimilation patterns and color spreading in neon patterns must be mediated by separate mechanisms is unwarranted; and (3) other than pointing to the way in which the overall organization of a scene affects the mode of color appearance, the neon spreading effect may not convey any extra theoretical relevance. PMID- 8351189 TI - Interocular suppression in normal and amblyopic subjects: the effect of unilateral attenuation with neutral density filters. AB - In normal subjects, binocular rivalry suppression takes time to build up (Wolfe, 1986a). The time courses of interocular suppression are different and heterogeneous in amblyopic subjects (de Belsunce & Sireteanu, 1991). In the present study, we found that, in normal observers, progressive reduction of one eye's stimulus luminance with neutral density filters produces time courses similar to those of amblyopic subjects. Conversely, in amblyopes, attenuation of the dominant eye's stimulus produces time courses similar to those of normal observers. Under conditions of balancing of the two eyes, amblyopes experience alternating suppression, similarly to binocular rivalry of normals. PMID- 8351190 TI - Realism of confidence in sensory discrimination: the underconfidence phenomenon. AB - This paper documents a very pervasive underconfidence bias in the area of sensory discrimination. In order to account for this phenomenon, a subjective distance theory of confidence in sensory discrimination is proposed. This theory, based on the law of comparative judgment and the assumption of confidence as an increasing function of the perceived distance between stimuli, predicts underconfidence- that is, that people should perform better than they express in their confidence assessments. Due to the fixed sensitivity of the sensory system, this underconfidence bias is practically impossible to avoid. The results of Experiment 1 confirmed the prediction of underconfidence with the help of present day calibration methods and indicated a good quantitative fit of the theory. The results of Experiment 2 showed that prolonged experience of outcome feedback (160 trials) had no effect on underconfidence. It is concluded that the subjective distance theory provides a better explanation of the underconfidence phenomenon than do previous accounts in terms of subconscious processes. PMID- 8351191 TI - The normal distribution in scaling subjective stimulus differences: less "normal" than we think? AB - The Gaussian, or "normal," distribution is routinely used to model distributions of subjective quantities. This practice rests on a trust in the central limit theorem, yet this theorem does not cover the case of a mixture of Gaussian distributions with different standard deviations, which yields a distribution that is heavier tailed than the Gaussian. In psychophysical judgment experiments, this may result, for example, from fluctuating or interindividually varying attention. Two candidates for describing this commonly encountered type of distribution are the logistic distribution and the t distribution with a small number of degrees of freedom. In reanalyses of experimental data on three category loudness comparisons, as well as in a Monte Carlo simulation, t(4) was found to model the underlying mixed inter- and intraindividual distribution of subjective loudness differences quite satisfactorily. PMID- 8351192 TI - The effects of background visual roll stimulation on postural and manual control and self-motion perception. AB - The effects of background visual roll stimulation on postural control, manual control, and self-motion perception were investigated in this study. In the main experiment, 8 subjects were exposed to wide field-of-view background scenes that were tilted and static, continuously rotating, or sinusoidally rotating at frequencies between 0.03 and 0.50 Hz, as well as a baseline condition. The subjects performed either a postural control task (maintain an upright stance) or a manual control task (keep an unstable central display horizontally level). Root mean square (RMS) error in both the postural and manual control tasks was low in the static tilt condition and extremely high in response to continuous rotation. Although the phases of the postural and manual responses were highly similar, the power and RMS error generated by the sinusoidal visual background stimulation peaked at a lower frequency in the postural task. Vection ratings recorded at the end of the postural and manual trials somewhat paralleled the frequency tuning differences between tasks, which a subsequent experiment showed to be the result of the differential motion of the central display rather than the differential positioning of the subject. In general, these results show that the dynamic characteristics of visual orientation systems vary according to the specific motor and/or perceptual system investigated. PMID- 8351194 TI - Development and application of a urodilatin (CDD/ANP-95-126)-specific radioimmunoassay. AB - Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [alpha-ANP(99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide. PMID- 8351193 TI - Oxygen-dependent expression of the erythropoietin gene in rat hepatocytes in vitro. AB - Since in juvenile rats the liver is the predominant site of erythropoietin (EPO) gene expression, we have used primary cultures of juvenile rat hepatocytes to establish and in vitro system for investigation of oxygen-dependent EPO formation. When isolated hepatocytes were incubated at reduced oxygen tensions for 18-48 h, we found increased secretion of EPO protein and elevated levels of EPO mRNA, as determined by RNas protection. This increase was maximal at 3% O2, where EPO mRNA levels after 18 h were approximately 15-fold higher than at 20% O2. The increase in EPO mRNA at low oxygen tensions was specific insofar as [3H]uridine incorporation, as a measure of total RNA synthesis, was reduced by approximately 50% at 3% O2, and it appeared to involve gene transcription since it was abolished in the presence of actinomycin D (35 microM). Significant increases in EPO mRNA were also observed in cells kept at 20% oxygen in the presence of cobalt chloride (50 microM) and nickel chloride (400 microM), but EPO mRNA levels achieved under these conditions were less than 7% of those in cells incubated at 3% oxygen. No increase in EPO mRNA levels was observed in cultures incubated at 20% O2 in the presence of cyclic dibutyryl-AMP (10 microM-3 mM), cyclic 8-bromoGMP (10 microM-1 mM), cyclohexyladenosine (1 microM), 5'-N ethylcarboxamidoadenosine (1 microM) and phorbol 12-myristate 13-acetate (3 nM). In the presence of 10% carbon monoxide, used to block haem proteins in their oxy conformation, EPO mRNA levels in hepatocytes incubated at low oxygen tensions were reduced to 63%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351195 TI - Hormonal stimulation of Ca2+ and Mg2+ transport in the cortical thick ascending limb of Henle's loop of the mouse: evidence for a change in the paracellular pathway permeability. AB - Recent studies from our laboratory have shown that in the cortical thick ascending limb of Henle's loop of the mouse (cTAL) Ca2+ and Mg2+ are reabsorbed passively, via the paracellular shunt pathway. In the present study, cellular mechanisms responsible for the hormone-stimulated Ca2+ and Mg2+ transport were investigated. Transepithelial voltages (PDte) and transepithelial ion net fluxes (JNa, JCl, JK, JCa, JMg) were measured in isolated perfused mouse cTAL segments. Whether parathyroid hormone (PTH) is able to stimulate Ca2+ and Mg2+ reabsorption when active NaCl reabsorption and thus PDte, is abolished by luminal furosemide was first tested. With symmetrical lumen and bath Ringer's solutions, no Ca2+ and Mg2+ net transport was detectable, either in the absence or in the presence of PTH. In the presence of luminal furosemide and a chemically imposed lumen-to-bath directed NaCl gradient, which generates a lumen-negative PDte, PTH slightly but significantly increased Ca2+ and Mg2+ net secretion. In the presence of luminal furosemide and a chemically imposed bath-to-lumen-directed NaCl gradient, which generates a lumen-positive PDte, PTH slightly but significantly increased Ca2+ and Mg2+ net reabsorption. In view of the observed small effect of PTH on passive Ca2+ and Mg2+ movement, a possible interference of furosemide with the hormonal response was considered. To investigate this possibility, Ca2+ and Mg2+ transport was first stimulated with PTH in tubules under control conditions. Then active NaCl reabsorption was abolished by furosemide and the effect of PTH on JCa and JMg measured. In the absence of PDte and under symmetrical conditions, no Ca2+ and Mg2+ transport was detectable, either in the presence or absence of PTH. In the presence of a bath-to-lumen-directed NaCl gradient, Ca2+ and Mg2+ reabsorption was significantly higher in the presence than in the absence of PTH. Finally, when active NaCl transport was not inhibited by furosemide, but reduced by a bath-to-lumen-directed NaCl gradient, PTH strongly increased JCa and JMg, whereas only a small increase in PDte was noted. In conclusion, these data suggest that PTH exerts a dual action on Ca2+ and Mg2+ transport in the mouse cTAL by increasing the transepithelial driving force for Ca2+ and Mg2+ reabsorption through hormone-mediated PDte alterations and by modifying the passive permeability for Ca2+ and Mg2+ of the epithelium, very probably at the level of the paracellular shunt pathway. PMID- 8351196 TI - Expression of myosin heavy and light chains changes during pregnancy in the rat uterus. AB - We investigated the in vivo expression of myosin heavy chains (MHC) and myosin light chains (MLC) in the rat uterus during pregnancy and post partum (p. p.). According to their antigenic reactivity, we observed two smooth-muscle-specific MHC (SM-MHC) of 204 kDa and 200 kDa (SM1 and SM2 respectively) and one non-muscle specific MHC band of 198 kDa (NM-MHC). Adult virgin female rats expressed SM1 and NM-MHC (65/35) but no SM2. During the first pregnancy NM-MHC expression decreased in favour of the SM1 form, the SM1/NM-MHC ratio being 82/12 after 20 days of pregnancy. SM2 is newly expressed in the first p. p. state, the SM1/SM2/NM-MHC ratio being 58/28/14 between 3 and 33 days p. p. During the second pregnancy, starting 34 days p. p., both SM2 and NM-MHC expression decreased, the SM1/SM2/NM MHC ratio being 85/0/15 after 20 days of pregnancy. Two protein bands of approximately 154 kDa and 145 kDa (sodium dodecylsulphate electrophoresis), designated SMP1 and SMP2 respectively, with the same immunoreactivity as the SM MHC were observed in vivo in the pregnant but not in the non-pregnant uterus. In addition, a Ca(2+)-independent protease, which uses MHC as substrate, is expressed in the pregnant but not in the non-pregnant rat uterus. Two isoforms of the 17-kDa MLC (LC17a and LC17b) exist in the rat uterus. Expression of the LC17a isoform increased during the first pregnancy from 46% in virgin rats to 65% in uteri of rats 20 days pregnant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351197 TI - Left ventricular pressure transmission to myocardial lymph vessels is different during systole and diastole. AB - In six open-thorax-anaesthetized dogs with paced hearts and a retrogradely cannulated epicardial lymph vessel, the sensitivity of myocardial lymph pressure to left ventricular pressure during systole and during diastole was determined. The lymph vessels were cannulated using PE-90 tubing, and lymph pressure was measured by connecting the cannula to a microtip pressure transducer. To obtain the systolic sensitivity, left ventricular pressure was changed by clamping the descending aorta, which caused left ventricular pressure to increase. The diastolic sensitivity was obtained from natural variation to left ventricular pressure caused by atrial contractions during induced long diastoles. The mean ratio of the pulse in lymph pressure to the pulse in left ventricular pressure was determined: systole: 0.069 +/- 0.013, n = 213, diastole: 0.76 +/- 0.16, n = 249 and, if possible, linear regression analysis between lymph and left ventricular pressure was performed. The systolic regression coefficients could be determined in six dogs and the diastolic coefficients in three dogs. During long diastoles lymph pressure variations are on average 76 per cent of those in the left ventricle. However, during systole, the sensitivity of lymph pressure to left ventricular pressure is more than ten times lower. It is not unlikely that the structural embedment of lymph vessels within the myocardium is such that volume variations by cardiac contraction are limited. PMID- 8351198 TI - Contractile protein gene expression in serum-free cultured adult rat cardiac myocytes. AB - The effects of two adhesion substrates (serum and laminin) and time in culture on the expression of genes encoding myosin heavy chain (MHC) isoforms and alpha skeletal actin were analysed in myocytes isolated from adult rat heart and maintained in serum-free culture. Relative messenger ribonucleic acid (mRNA) abundances were quantitated by dot-blot analysis. Gene expression was not influenced by the substrate used. Time in culture induced a decrease in total mRNA abundance and an up-regulation of beta-MHC and alpha-skeletal actin genes. It is proposed that atrophy of adult myocytes is associated with a pattern of gene expression similar to the fetal program. PMID- 8351199 TI - Neuropeptide Y potentiates calcium-channel currents in single vascular smooth muscle cells. AB - The effect of neuropeptide Y (NPY) on Ca(2+)-channel currents in isolated vascular smooth muscle cells was studied with the perforated-patch recording technique. Using Ba2+ (10 mM) as the charge carrier, inward currents sensitive to Cd2+ and nifedipine were potentiated by NPY in a concentration-dependent manner. The threshold concentration for the potentiating effect of NPY was 50 nM and reached a maximum at 150 nM. NPY shifted the steady-state activation curve to less positive membrane potentials by about 6 mV so that the potentiating effect was most prominent near the activation threshold of the current. It had no effect on steady-state inactivation of the current. These results suggest that NPY may potentiate vasoconstriction by promoting calcium entry through L-type voltage dependent Ca(2+)-channels. PMID- 8351200 TI - Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. AB - A description is given of the implementation of infrared differential interference contrast (IR-DIC) video microscopy to an upright compound microscope. Using the improved resolution offered by IR-DIC a procedure is described for making patch-pipette recordings from visually identified neuronal somata and dendrites in brain slices. As an example of the application of this technique to electrophysiological recordings from small neuronal processes in brain slices we describe whole-cell current-clamp and cell-attached and excised patch-clamp recordings from the apical dendrites of layer V pyramidal neurons in slices of rat neocortex. PMID- 8351201 TI - Agonist-induced intracellular Ca2+ transients in HT29 cells. AB - In the present study we have investigated the mechanism of intracellular Ca2+ activity ([Ca2+]i) changes in HT29 cells induced by adenosine triphosphate (ATP), carbachol (CCH), and neurotensin (NT). [Ca2+]i was measured with the fluorescent Ca2+ indicator fura-2 at the single-cell level or in small cell plaques with high time resolution (1-40Hz). ATP and CCH induced not only a dose-dependent [Ca2+]i peak response, but also changes of the plateau phase. The [Ca2+]i plateau was inversely dependent on the ATP concentration, whereas the CCH-induced [Ca2+]i plateau increased at higher CCH concentrations. NT showed (from 10(-10) to 10(-7) mol/l) in most cases only a [Ca2+]i spike lasting 2-3 min. The [Ca2+]i plateau induced by ATP (10(-6) mol/l) and CCH (10(-5) mol/l) was abolished by reducing the Ca2+ activity in the bath from 10(-3) to 10(-4) mol/l (n = 7). In Ca(2+)-free bathing solution the [Ca2+]i peak value for all three agonists was not altered. Using fura-2 quenching by Mn2+ as an indicator of Ca2+ influx the [Ca2+]i peak was always reached before Mn2+ influx started. Every agonist showed this delayed stimulation of the Ca2+ influx with a lag time of 23 +/- 1.5 s (n = 15) indicating a similar mechanism in each case. Verapamil (10(-6)-10(-4) mol/l) blocked dose dependently both phases (peak and plateau) of the CCH-induced [Ca2+]i increase. Short pre-incubation with verapamil augmented the effect on the [Ca2+]i peak, whereas no further influence on the plateau was observed. Ni2+ (10( 3) mol/l) reduced the plateau value by 70%. PMID- 8351202 TI - Simultaneous measurement of intracellular pH and contraction in uterine smooth muscle. AB - Changes in intracellular pH (pHi) are thought to produce large changes in force production in the uterus. There have however, been no simultaneous measurements of pHi and force in the uterus and therefore no direct information is available about the relation between the two. We have used carboxy-SNARF (a pH-sensitive fluorophore) in small strips of longitudinal myometrium and obtained simultaneous measurements of pHi and force. SNARF did not alter contractile function, and continuous measurements of pHi could be made for 2 hours. The mean resting pHi (7.16) was similar to that reported previously. Application of weak bases rapidly raised pHi, in a concentration-dependent manner, followed by a gradual restoration of pHi to resting levels. Alkalinization greatly increased the frequency of contractions, often accompanied by a small increase in their amplitude. Removal of base produced a rebound acidification which transiently abolished contractions. Direct acidification of the cytoplasm, by application of weak acid, also abolished contractions. However the alkalinization which accompanied removal of acid, produced variable effects on force. PMID- 8351203 TI - Effects of divalent cations on the activation of a calcium-dependent potassium channel in hippocampal neurons. AB - The activation of a calcium-dependent K+ channel K(Ca) in cultured hippocampal neurons has been studied after the addition, to the internal solution, of the divalent cations magnesium (Mg2+), strontium (Sr2+) or barium (Ba2+). With physiological K+ across inside-out patches and Ca2+ present at 0.2 mM in the bath solution, a 90-pS channel was activated with an open probability in excess of 75%. When the internal Ca2+ was reduced to levels near 5 microM, the channel-open probability was significantly diminished. However, if 0.2 mM concentrations of either Mg2+ or Sr2+ were added to the internal solution, the open probability was increased to a value close to original level. In the presence of internal Ca2+ at 0.1 microM, the K(Ca) channel was not active and was not activated with the addition of 0.2 mM Mg2+ or Sr2+ to the internal solution. Thus, Mg2+ or Sr2+ were not able to active K(Ca) in the absence of Ca2+; however, both of these divalent cations could potentiate the Ca(2+)-induced activation of K(Ca) if internal Ca2+ was near 5 microM. The results indicate that Mg2+ could have a role as an internal modulator of K(Ca) in the Ca(2+)-dependent regulation of excitability in nerve membrane. Replacement of Ca2+ with Ba2+, or addition of Ba2+ to Ca containing solutions, caused significant decreases in the channel-open probability for K(Ca). The action of Ba2+ was primarily mediated by a decrease in the frequency of channel opening. At a concentration of 5 microM, Ba2+ diminished the channel-open probability by one-half. PMID- 8351204 TI - Endogenous MLC2 phosphorylation and Ca(2+)-activated force in mechanically skinned skeletal muscle fibres of the rat. AB - A method has been developed for measuring the level of phosphorylation of myosin regulatory light chains (MLC2) by the endogenous myosin light chain kinase in mechanically skinned skeletal muscle fibres. The method was used to characterize the endogeous MLC2 phosphorylation capacity of single fast-twitch fibres from the rat and to investigate the relationship between the endogenous MLC2 phosphorylation and the Ca(2+)-activated force. The results show that (1) about 50% of MLC2 were 32P-phosphorylated after activation of the skinned fibre preparation by 30 microM [Ca2+] for longer than 30 s, but that there was variability between fibres; (2) most of the endogenous phosphorylating system diffused out of the skinned fibre preparation after 5 min exposure to an aqueous solution; (3) the MLC2 phosphorylation by the endogenous phosphorylating system followed with a delay of the order of 1-2 s after the sudden rise in [Ca2+] from below 10 nM to 30 microM; and (4) the sensitivity of the contractile apparatus to Ca2+ was markedly increased when the MLC2 were phosphorylated by the endogenous phosphorylating system following a rise in [Ca2+]. The Kd for MgATP of the endogenous MLC2 phosphorylating system was estimated to be less than 300 microM. These results unequivocally demonstrate that prolonged activation of the fast twitch muscle fibre leads to increased Ca2+ sensitivity of the contractile apparatus and that mechanically skinned fibres can be successfully used to study the regulation of the endogenous MLC2 phosphorylation capacity at single muscle fibre level. PMID- 8351205 TI - Potentiation of sarcoplasmic reticulum Ca2+ release by 2,3-butanedione monoxime in crustacean muscle. AB - The effect of the chemical phosphatase 2,3-butanedione monoxime (BDM) on various aspects of excitation/contraction coupling in crustacean muscle was investigated. Despite having a depressant effect on vertebrate skeletal and cardiac muscle, BDM was a potentiator of contraction in crustacean muscle. At concentrations of 1-3 mM BDM caused an increase of potassium contractures in bundles of fibers isolated from crayfish muscle. At higher concentrations BDM caused oscillatory contractions by itself. In single voltage-clamped cut muscle fibers loaded with rhod-2, BDM (0.5-2 mM) potentiated the magnitude and duration of intracellular Ca2+ transients elicited by depolarization. At the same time BDM did not affect the rate of Ca2+ removal from the myoplasm under conditions where Ca2+ release was blocked by tetracaine. Nor did BDM increase Ca2+ entry; in fact it caused a decrease in the amplitude of the inward Ca2+ current (ICa). In microsomes isolated from lobster muscle, BDM also potentiated Ca2+ release induced by caffeine and at higher concentrations (above 3 mM) induced release by itself. At the same time it had little effect on Ca2+ uptake. These results indicate that BDM potentiates Ca2+ release in crustacean muscle possibly by dephosphorylation of the Ca(2+)-release channel. PMID- 8351206 TI - Modification of K-ATP channels in pancreatic beta-cells by trypsin. AB - The inside-out configuration of the patch-clamp method was used to study the effects of trypsin on the activity of ATP-sensitive potassium (K-ATP) channels from isolated mouse pancreatic beta-cells. Trypsin (20 micrograms/ml) irreversibly enhanced channel activity around twofold by reducing the interburst intervals without altering the burst kinetics. No effect on the single channel conductance or the inward rectification produced by internal Mg2+ was observed: however, the protease did reduce the inhibitory effect of Mg2+ on channel activity. Trypsin both prevented rundown of K-ATP channel activity and reactivated the channels after complete rundown. These effects of trypsin were absent in the presence of trypsin inhibitor. The protease also reduced the inhibitory effect of ATP on channel activity, increasing the dissociation constant from 7 to 49 microM. Trypsin removed the activating effect of ADP (0.1 mmol/l) on channel activity and reduced the inhibitory effect of tolbutamide (0.5 mmol/l). Carboxypeptidase A did not activate K-ATP channels in excised patches, although it was able to slightly reactivate channels after complete rundown, whereas chymotrypsin increased K-ATP channel activity but it did not produce reactivation. The effects of papain were similar to those of trypsin. PMID- 8351207 TI - The energetics of shortening amphibian cardiac muscle. AB - An isolated amphibian cardiac muscle preparation, toad ventricular strip, was used to examine the energetics of shortening. Simultaneous measurements of force and length changes and the associated heat production were made. Both the isometric heat/stress and the enthalpy (heat+work)/load relationships were similar to those previously reported in mammalian cardiac muscle. The activation metabolism was higher in this preparation and, like its mammalian counterpart, was length dependent. The heat production measured in an isometric contraction was approximately 50% higher than that observed at the same stress level in rodent mammalian cardiac muscle. This did not affect the maximum isotonic mechanical efficiency (work divided by enthalpy) of the preparation which, at an afterload of 20% of the maximum stress was 18.1 +/- 1.7% (n = 8). There was no evidence for a shortening heat component in this preparation during isotonic contractions. It appears therefore that the energetics of shortening amphibian cardiac muscle closely resemble the energetics of mammalian cardiac tissue. PMID- 8351208 TI - Forces involved in length changes of cochlear outer hair cells. AB - Motion or force generation of outer hair cells may contribute to active modulation of cochlear mechanics. In order to determine the force involved in length changes of outer hair cells, a new in vitro method was used. In the first series of experiments, apical and basolateral extracellular spaces of outer hair cells of the guinea-pig cochlea were separated. Changes of the voltage between the two extracellular spaces induced reversible, proportional changes of the cell length of 4.4 nm/mV if the cell had a length of 80 microns. In the second series of experiments, cell elongations in response to negative pressure applied to the basal end of the cells were measured and corrected for frictional effects. From these data, the compliance of the longitudinal axis of the hair cells was calculated. It was 220 +/- 130 m/N (n = 25) and 240 +/- 170 m/N (n = 24) for cells of the third and fourth cochlear turns, respectively, if the water permeability of the cell membrane was neglected. If the water permeability was taken into account, the compliance was probably around 500 m/N [corrected]. Thus, a mechanism that changes the cell length by 1 microm must generate a static force of at least around 2 nN in an outer hair cell of the organ of Corti [corrected]. Electromotility of outer hair cells, induced by changes of the electrical potential difference across the outer hair cell, is a mechanism that generates this force. PMID- 8351210 TI - A cruel cut. PMID- 8351209 TI - Early effects of aldosterone on the basolateral potassium conductance of A6 cells. AB - Aldosterone increases the basolateral conductance in target epithelia. The basolateral membrane of tight epithelia contains two different types of K+ conductances (GK), a "resting" and a volume-activated GK. We have studied the early effects (at 4 hours) of 500 nmol/l aldosterone on the basolateral membrane GK of A6 cells (a Xenopus laevis kidney cell line), after the permeabilization of the apical membrane with amphotericin B. In the presence of a 97 to 3 mmol/l apical to basolateral K+ gradient, the "resting", inward rectifying GK was similar in control and aldosterone treated cells. In contrast, aldosterone induced a 2-fold increase of the volume-activated quinidine sensitive GK. PMID- 8351212 TI - Pink's precedent. PMID- 8351211 TI - On the move. PMID- 8351213 TI - Sweet surrender. PMID- 8351214 TI - Whistle while you work? PMID- 8351216 TI - Stress: smart delivery. PMID- 8351215 TI - Complementary medicine. Acupuncture. PMID- 8351217 TI - Learning disabilities: riding high. PMID- 8351218 TI - Career development--the hard sell. PMID- 8351219 TI - A friend in need. PMID- 8351220 TI - Junior doctors--passing the buck. PMID- 8351221 TI - Yesterday once more. PMID- 8351222 TI - Waiting for Dr Godot. PMID- 8351223 TI - Systems of life. The eye and vision. 2. PMID- 8351224 TI - Shock of the new. RCM supplement. PMID- 8351225 TI - Extend with care. RCM supplement. PMID- 8351226 TI - Tired and tested. RCM supplement. PMID- 8351227 TI - Seize the day. RCM supplement. Interview by Tricia Reid. PMID- 8351228 TI - [Effect of long term treatment with prednisone on remodeling of cancellous and cortical bone in dogs]. AB - The effect of 7 month prednisone administration on cancellous and compact bone remodeling in dogs was evaluated by means of histomorphometric and tetracycline labeling methods. It was found that treatment with prednisone resulted in decrease of bone mass which was caused by increased bone resorption as well as considerable diminution of bone formation. In the iliac bone those were manifested by increase in resorption of trabecular surface, decrease in osteoid surface, and reduction in the osteoid thickness, indicating, with a simultaneous decrease in mineralization rate, slowing down of the appositional rate of newly formed bone tissue. In the rib cortical bone treatment with prednisone resulted in increase of the resorption sites together with decrease of the formation sites and tetracycline-labeled osteons. Reduction in the osteoid thickness as well as in the mineralization rate was also observed. The changes of bone remodeling parameters due to prednisone, although proceeding in the same direction in both types of bone tissue, were more marked in the spongy bone than in the compact bone. PMID- 8351229 TI - [Atrial natriuretic peptide in rheumatic mitral valve disease]. AB - The aim of the study was to analyze atrial natriuretic peptide (ANP) plasma level in patients with rheumatic mitral valve disease in correlation with NYHA functional class and selected hemodynamic parameters based on noninvasive diagnostic procedures. Echocardiographic (2-D, Doppler) and X-ray chest examination were performed to measure left atrium dimension, mitral gradient and relative heart volume (RHV). Control group consisted of 10 healthy subjects. ANP were measured (radioimmunoassay) in 35 patients before valve replacement. Mean values for ANP were significantly elevated in all patients compared to control group (p < 0.001). No significant difference between ANP secretion in pts with sinus rhythm (mean ANP level 25.3 +/- 6.9 pmol/l) and pts with atrial fibrillation (mean ANP level 26.7 +/- 7.6 pmol/l) occurred. Positive correlation between left atrium dimension and ANP level were found (r = 0.964) and also between RHV and ANP level (r = 0.9) and between NYHA class and ANP level (r = 0.63). The conclusion is that ANP secretion is elevated in all patients with heart failure due to mitral valve disease proportional to its stage. PMID- 8351230 TI - [Volume of the functioning gallbladder and its emptying in patients with progressive systemic sclerosis]. AB - The aim of the study was to measure the gallbladder volume (GV) and its emptying after meal stimulus in patients with progressive systemic sclerosis (PSS). 18 women with PSS, aged 49.8 +/- 9.5 yr, participated in the study. Control values were obtained from 30 healthy women aged 26.5 +/- 3.5 yr. The duration of PSS symptoms ranged from 2 to 25 yr. Subjects with gallstones or cholecystitis as well those receiving drugs affecting the gastroduodenal motor function were excluded from the study. GV was measured according to Dodds et all (1985) with the real-time sonographic apparatus (Sonoline SL Siemens, Germany), after an overnight fast and after a test meal. Measurements were repeated in 10 min intervals through a 40 min duration of the study. Similar volumes of fasted gallbladder were found in the PSS group and in the control group: 25.4 cm3, SEM 3.0 (PSS), vs. 20.9 cm3, SEM 1.6 (control), p > 0.05. There was not any correlation between the fasted GV and duration of the disease symptoms. The test meal evoked in both groups a similar trend of the decrease in the GV during 40 min and the increase in the ejection fraction at this time. Although the changes observed were statistically not significant (p > 0.05) there were small differences in the gallbladder ejection fraction in two patients, not exceeding 14% and 18%, and being apparently below of any individual value in the control group. CONCLUSION: the gallbladder motor function is very rarely disturbed in patients with PSS. PMID- 8351231 TI - [Studies of immunoglobulin surface expression in lymphocytes of peripheral blood, bone marrow and lymph nodes in patients with B-cell chronic lymphocytic leukemia]. AB - The expression of surface immunoglobulins (SIg) on peripheral blood, bone marrow, and lymph node lymphocytes was studied in a group of 10 patients with B cell chronic lymphocytic leukaemia. In 4 patients differences in the SIg phenotypes were found when cells from blood, bone marrow and lymph nodes were examined. Peripheral blood lymphocytes were characterized as a monoclonal B cell population whereas in the marrow or lymph node lymphocytes a tendency toward poly-clonality was found. We suggest that these differences reflect the origin of the initial leukaemic transformation: intra versus extra-medullar. In case of intramedullary origin of leukaemia the transformed clone infiltrates subsequently lymph nodes or other lymphoid structures. In leukaemia of extra-medullar origin the bone marrow is infiltrated later and therefore the tendency toward polyclonal SIg picture of the bone marrow lymphocytes contrasts with the monoclonality of the peripheral blood cells. PMID- 8351233 TI - [Platelet function in patients with diabetes mellitus]. PMID- 8351232 TI - [Does hypoglycemic treatment with gliclazide and gliquidone affect platelet function in type II diabetic patients?]. AB - The estimation of the influence of gliclazide and gliquidone treatment on platelet function in type II diabetic patients was undertaken in the study. Aggregation parameters were assessed before and after the change of hypoglycemic therapy. Gliclazide was applied in the group I (11 patients, mean age 63.1 +/- 7.22 years, duration of diabetes 5.63 +/- 2.98 years), group II (19 patients, mean age 58.3 +/- 12.4 years, duration of diabetes 7.1 +/- 2.4) received gliquidone. The reference group consisted of 10 healthy volunteers (mean age 51.7 +/- 6.9). Aggregation parameters (threshold ADP concentration, intensity and velocity of the aggregation) were measured in examined groups of subjects. Metabolic control was estimated basing upon spectrophotometric measurement of fructosamine level. Significant increase in threshold ADP concentration (1.89 +/- 0.47 mumol/l before and 2.36 +/- 0.58 mumol/l after the treatment change p < 0.05) in group II was found. Threshold ADP concentration did not change significantly in group I (2.5 +/- 0.8 mumol/l before v 2.14 +/- 0.68 mumol/l after treatment). Significant decrease in the aggregation intensity was found in both groups (in group I 8.48 +/- 1.7 before v 6.39 +/- 2.17 after; in group II 7.35 +/- 1.73 before v 6.05 +/- 1.6 after 1 month treatment--both p < 0.05). The aggregation velocity did not change significantly (group I 61. +/- 11 before v 51.3 +/- 18.7 after, group II 63.2 +/- 14.8 and 62.8 +/- 13.7 respectively). Reference group values were ADP 2.7 +/- 0.16, intensity 6.22 +/- 0.53, velocity 63.2 +/- 2.2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351234 TI - [Lipid disturbances in kidney transplant patients]. PMID- 8351235 TI - [Renal biopsy in the aged]. AB - Pathological findings in urinalysis in the aged persons are usually thought to be caused by pathologic processes other than glomerulopathy. Histological evaluation of renal tissue in older patients is extremely difficult due to coexistence of involuntary changes-hyalinosis, increase in mesangial matrix content, and vascular changes. The aim of the study was to evaluate frequency of glomerulonephritis, both primary and secondary in persons older than 60. In this group, as compared to the younger people the secondary glomerulonephritis was more frequent, amyloidosis and vasculitis nodosa being the most frequent. In primary glomerulonephritis mesangiocapillary type dominate, quite often some tendency to hyalinization could be observed. Renal biopsy is useful as a diagnostic tool in both the aged and young. It should be performed regardless the patients age. PMID- 8351236 TI - [Assessment of outcome in treatment of cardiac shock after myocardial infarction with intravenous streptokinase]. AB - In 1986 a prospective randomized study coordinated by the Institute of Cardiology in Warsaw was started in 10 teaching cardiology hospitals in Poland for assessment of the results of treatment with intravenous streptokinase infusion in acute myocardial infarction. The studied population comprised 927 patients admitted to intensive treatment units within 6 hours after the onset of infarction pain. For the groups treated with streptokinase or heparin 752 patients were selected at random. In 175 cases the administration of streptokinase was contraindicated. These patients received conventional treatment and served as controls. The age of the patients was from 38 to 70 years, mean age 57.6 +/- 9.3 years. In 105 out of 927 cases cardiac shock was diagnosed. In the groups of early shock during hospitalization the death rate was 82%. No statistically significant difference was found in the death rates between patients with cardiac shock treated with heparin or with streptokinase. PMID- 8351237 TI - [Treatment of hypertension in patients with diabetes]. PMID- 8351238 TI - Pathological features of intestinal microsporidiosis in HIV positive patients. A report of 13 new cases. AB - Enterocytozoon bieneusi is a microsporidian parasite found only in the enterocytes of the small bowel of HIV positive patients, producing chronic diarrhea and malabsorption. Since January 1990, we have seen the 13 first Mediterranean cases, diagnosed on duodenal pinch biopsy samples. Diarrhea was the major symptom in all instances, and E. bieneusi was the sole identified pathogen in 6 cases. The diagnosis was made on HES or Giemsa-stained paraffin sections and on Giemsa-stained smears (9 cases). In 3 cases, the parasite was also found on ileal biopsies, but was never encountered in the colonic mucosa. In all patients, transmission electron microscopy of the duodenal mucosa was used, and it confirmed the diagnosis of intestinal microsporidiosis. No instance with negative optic examination had evidence of an infection by E. bieneusi with electron microscopy. Due to the small size of the spores, routine fecal parasitological diagnosis is still a difficult procedure, but it is possible that greater experience may avoid many of today's invasive investigations. Cytologic and histologic routine examination of paraffin sections of the distal duodenal or ileal mucosae is a reliable method to diagnose intestinal microsporidiosis in HIV positive patients with diarrhea. PMID- 8351240 TI - Association of breast cancer and meningioma. Report of 12 new cases and review of the literature. AB - We report 12 new cases of female breast cancer associated with intracranial meningiomas, inclusive of autopsy study. At the time of death the patients' age ranged from 52 to 95 years (average 70.6 years). Breast carcinomas were documented ante mortem in 11 cases and at autopsy in 1. Meningiomas were diagnosed at autopsy (10 cases) or in vivo (2 cases). The diagnosis of meningioma antedated that of mammary carcinoma in only one patient. Histologically, the cancers were of ductal (11 cases) and lobular infiltrating (1 case) types and showed a variable malignancy grade. Widespread extracranial metastases were present at autopsy in 7 cases. Brain metastases were seen in 1 case. Neurologic signs were referred in 4 subjects. Four breast cancers and one meningioma showed immunoreactivity for progesterone receptors, whereas all the cases were negative for estrogen receptors. In one case, metastatic breast carcinoma tissue was present within a psammomatous meningioma. A brief review of the literature, which includes 14 similar observations, is reported. Although the association of breast cancer and meningioma is still difficult to explain, its clinical implications are important and deserve proper attention. A proper work up in patients with suspected intracranial metastases is recommended so that resectable meningiomas are not mistaken for metastases. PMID- 8351239 TI - Vla-3 distribution in normal and neoplastic non-lymphoid human tissues. AB - Using monoclonal antibody (mAb) M-Kid 2 to the alpha 3 beta 1 heterodimer, we have evaluated immunohistochemically the in vivo expression of the Vla-3 integrin in normal and transformed non-lymphoid human tissues. In normal tissues the alpha 3 beta 1 complex displays a polarized distribution at the baso-lateral aspect of most keratinizing and glandular epithelia. In addition the integrin is detected in perineurium, basal lamina of smooth muscular fibers, vascular media, podocytes and Bowman's capsule, myoepithelial cells of the parotid and breast, and in pulmonary alveoli. Neoplastic transformation is associated with qualitative and quantitative changes in expression of this integrin. The loss of polarized distribution often occurs in various malignancies. Furthermore, a significant decrease in expression occurs in 13% of the colon-rectum carcinomas, 75% of the ductal invasive, and 40% of the lobular invasive breast carcinomas. Among the lung malignancies tested, the small cell lung carcinomas (SCLC) were found to be consistently unreactive with mAb M-Kid 2. Analysis of Vla-3 expression in established tumor cell lines demonstrated that the integrin is almost invariably expressed by the plastic adherent cell subpopulations. PMID- 8351242 TI - Clear cell chondrosarcoma of bone. A report of three cases with immunohistochemical and affinity histochemical observations. AB - Clear cell chondrosarcoma, a subtype and separate entity from the traditional chondrosarcoma, is characterized by its special histologic features, site of predilection, slow growth and better prognosis. Three cases are presented with elucidation of clinicopathologic correlation and detection by the ABC immunohistochemical method using several antibodies. The observation of positive reaction to S-100 protein (S-100), vimentin (Vim), alpha 1-antichymotrypsin (AACT) and lysozyme (Lyso) by the tumor cells of clear cell chondrosarcoma, similar to traditional chondrosarcoma and chondroblastoma, proves that this tumor has its origin in the cartilaginous tissue. It was found for the first time that the clear cell chondrosarcoma was positive for wheat germ agglutinin (WGA) and concanavalin A (Con A). The authors believe that clear cell chondrosarcoma may result from the anaplastic changes of chondroblastoma cells into another subtype of that tumor. The osteoclast-like multinucleated giant cells (MGC), retaining the antigens of phagocytes, are not considered to be neoplastic. PMID- 8351241 TI - Flow cytometric DNA analysis as prognostic factor in human breast carcinoma. AB - Fresh tumour tissue from 198 primary invasive breast carcinomas was analysed by DNA flow cytometry. 108 tumours were non-diploid. A significantly higher proportion of non-diploid tumours was found among node-positive patients, patients with oestrogen receptor negative tumours and among patients with ductal carcinomas. The survival of patients with diploid and non-diploid tumours was not significantly different (p = 0.1). Totally, 145 tumours were analyzed with respect to S-phase fraction (SPF). The distribution of SPF was different in diploid and non-diploid tumours. A low SPF group, defined as the lower SPF quartile (< or = 4.6% in diploid and < or = 8.5% in non-diploid tumours), was associated with highly differentiated tumours and oestrogen receptor positive tumours. Histological grading revealed a highly significant correlation to SPF. 57% of ductal carcinomas grade I (8 out of 14), 30% of ductal carcinomas grade II (20 out of 67) and 5% of ductal carcinomas grade III (2 out of 37) had a low SPF. Patients within the low SPF group had a significantly longer survival than had patients within the high SPF group (p = 0.006). In a multivariate analysis the SPF was found to be an additional prognostic factor next to node status and ER status. PMID- 8351243 TI - Nucleolar organizer regions related to morphometry, flow cytometry, sex steroid receptor content, tumour histology and prognosis in female breast cancer. AB - Nuclear organizer regions (Ag-NORs) were visualized and enumerated in biopsy specimens from 158 breast carcinomas and the results were correlated with clinical, histological, quantitative prognostic factors and survival. The number of Ag-NORs was related significantly to histological type (p = 0.003), tubule formation (p = 0.013), histological grade (p < 0.001), mean nuclear area (p < 0.001), SD of nuclear area (p < 0.001), DNA ploidy (p < 0.001), S phase fraction (p = 0.001), mitotic index (p < 0.001), estrogen receptor content (p < 0.001) and progesterone receptor content (p < 0.001). Ag-NORs were independent of tumour size and axillary lymph node status. Neither in the entire cohort (p = 0.16) nor in axillary lymph node negative tumours (p = 0.11) was the number of Ag-NORs related to survival although a clear trend was observed between lowered survival probability and high Ag-NOR count. In multivariate analysis Ag-NORs had no independent prognostic value. The results confirm previous results in that Ag NORs have no practical prognostic value over already established prognostic factors in breast cancer. PMID- 8351244 TI - Rhabdomyosarcomas with primary presentation in the skin. AB - Five primary and two metastatic rhabdomyosarcomas (RMS) with primary presentation in the skin were studied by conventional light microscopy and immunohistochemistry. These cases account for only 0.7% of the 682 cases of RMS collected at two large institutions with a main interest in soft tissue tumors. All but one tumor, which was an embryonal RMS, corresponded to the alveolar subtype. The myogenic nature of the tumor cells was supported by the immunophenotype including positive reactions for vimentin, desmin, and muscle actin. Clinical findings included a male predominance, young age of the patients and the location of all primary cutaneous RMS in the face. One of the two metastatic RMS presented at birth with a clinical picture highly suggestive of congenital metastatic neuroblastoma, notably because of a 100-fold amplification of the N-myc copy number. Thus, this case illustrates again that an amplification of the N-myc oncogene is not restricted to neuroblastoma, but may also occur in other tumor types. PMID- 8351245 TI - Extracerebral toxoplasmosis in AIDS. Histological and immunohistological findings based on 80 autopsy cases. AB - Despite the great amount of literature concerning toxoplasmic encephalitis in AIDS patients, little is known about extracerebral toxoplasmosis. Therefore we conducted a study of 80 autopsy cases to estimate the frequency of extracerebral toxoplasmosis. A control group of 50 cases was completely negative for all markers applied. In 35 of the 80 AIDS-cases (43.7%), organisms could be detected. In 13 cases (16.2%) there was an extracerebral toxoplasmosis; 4 cases (5%) showed only extracerebral involvement and in 9 cases (11.2%), extracerebral toxoplasmosis occurred in combination with cerebral manifestations. In 22 cases (27.5%), only cerebral toxoplasmosis was found. The following organs were involved: cardiac muscle (15%), lungs (6.2%), liver (5%), pancreas (5%), gastrointestinal tract (6.2%), adrenal glands (5%), lymph nodes (5%) and testis (3.7%). In individual cases further organs, not mentioned above, were involved. Pseudocysts could be demonstrated within necroses and inflammatory foci by conventional staining, whereas trophozoites became apparent only immunohistologically. PMID- 8351246 TI - Dissociation of clinical manifestation and histopathology in the course of mesangial injury by anti-thymocyte antibody. AB - Intravenous administration of heterologous anti-thymocyte antibodies, which react with rat mesangial cells, induced minimal mesangiolysis (6 hours to 3 days) followed by mesangial hypercellularity. Moreover, autologous immunoglobulins appeared in the mesangium within 1 or 2 weeks. At the same time, electron microscopy demonstrated mesangial deposits. Accompanying these pathological alterations, significant proteinuria developed. To accelerate an acute autologous immune reaction, rats were preimmunized with rabbit IgG prior to the injection of anti-thymocyte antibodies. They revealed marked mesangiolytic lesions 3 days after injection with deposition of autologous immunoglobulins and C 3 in the mesangium. In contrast, there was no significant proteinuria. Thus, mild pathological alterations in the mesangium induced by heterologous and subsequent autologous immune reactions caused proteinuria, and accelerated immune injury to the mesangium produced severe mesangiolysis without proteinuria. Based on these findings, it is suggested that the time-lapse between heterologous and autologous immune reactions to the mesangium influences the pathological alterations and clinical manifestations occurring in mesangial injury by anti-thymocyte antibody. PMID- 8351247 TI - Light microscopic and immunohistochemical evaluation of vascular and neural invasion in colorectal cancer. AB - One hundred and sixty consecutive surgically removed colorectal carcinomas were investigated on histological sections stained with Hematoxylin and Eosin (H & E). Vascular and neural neoplastic invasion was found in 49 (30.6%) and 50 (31.3%) patients. In addition, immunohistochemical investigation was performed on step sections to those stained with H & E in the first 50 patients, using anti-human Factor VIII related antigen, anti-actin and anti-protein S 100 antisera. The percentages of positive cases for vascular invasion in this group of 50 patients were 20% on H & E sections and 62% on those stained with anti-Factor VIII and anti-actin antisera. Neural infiltration was identified in 14% of cases on H & E sections and in 70% of cases on anti-protein S 100 treated sections. Since vascular and neural infiltration are known to be ominous prognostic factors, their identification has great clinical relevance. The use of these simple immunohistochemical stains, using readily available antisera on formalin-fixed material, is recommended as routine procedure in surgical pathology laboratories. PMID- 8351248 TI - Mycoplasma-like organism induced murine cardiac microvasculopathy. A transmission electron microscopic study. AB - Mycoplasma-Like Organisms [MLO] are intracellular cell wall deficient bacteria that cause ocular chronic vasculitis in man and chronic vascular disease in plants. Since MLO do not grow in culture, diagnosis of MLO-induced disease requires identification of the organisms by electron microscopy. Ultrastructurally, MLO appear as pleomorphic tubulo-spherical and filamentous organisms. In human ocular disease MLO have been detected in parasitised leucocytes and retinal pigment epithelial cells. We have previously reported the results of injecting MLO infected human vitreous into mouse eyelids. Two thirds of the mice developed chronic disease at the inoculation site, but, more importantly, the mice also developed lethal systemic MLO disease. Carditis with histologic features similar to those of various types of human carditis occurred in 18% of the mice. This report describes the ultrastructural features of the cardiac microvascular MLO disease in those 18 mice that died of carditis after inoculation with human MLO-infected vitreous. MLO were identified in leucocytes and endothelial cells of the murine vascular lesions. The vascular lesions were characterized by destruction of vessel walls as well as proliferation of endothelial cells. Electron dense deposits were seen in basement membranes and pericytial tissues. Similar features have been described in other bacterial vascular infections and in human idiopathic carditis. We suggest that MLO could be a cause of human cardiovascular disease and should be looked for in such cases. PMID- 8351249 TI - Departmental audit in histopathology. AB - Audit is now part of any laboratory service. Histopathology is no exception, and we have set up a system which allows us to review 4% of our specimens. These specimens are identified using a random number generator and reviewed by a consultant pathologist. Both slides and wet specimens are reviewed and graded according to a set scheme. The results from the first year of operation (1990) show a high rate of accuracy with no serious diagnostic disagreements between the auditor and the reporting pathologist. However, some errors which we would wish to prevent were detected and the audit has allowed us to take corrective measures. In our opinion, this form of audit is useful and necessary to maintain good clinical practice. The cost is considerable--histopathology is by its nature labour intensive. Recognition of this fact by health boards is essential if such systems are to continue. PMID- 8351250 TI - Genetic alterations in a malignant schwannoma from a patient with neurofibromatosis (NF1). AB - In a patient with neurofibromatosis (von Recklinghausen disease; NF1), normal lymphocytes, five cutaneous neurofibromas, and tumour tissue from a recurrence of a malignant schwannoma were analysed for genetic alterations. Eleven DNA markers located on chromosome 17 and nine randomly chosen markers representing chromosomes 1, 2, 3, 4, 5, 6, and 11, were analysed. High resolution Giemsa banding of lymphocytes revealed no chromosomal rearrangement. The DNA from the neurofibromas were all found to have the same restricted fragment length polymorphism pattern as the constitutional DNA from the patient. In the malignant schwannoma a complete loss of one allele was found at polymorphic loci on chromosome arm 17p. One gene copy of the TP53 gene (17p13.1) and the NF1 gene (17q11.2) was lost, as was one copy of the PGA gene (11q13). No mutations were detected in the mutational hotspots of the TP53 gene. Partial losses were detected at three loci on chromosomes 1, 2 and 6, indicating a clonal variation within the tumour since histological evaluation disclosed no normal tissue in the analysed specimen. Our data indicate that the NF1 gene may function as a tumour suppressor gene, and that, either by effect of dose reduction or complete inactivation, both the NF1 gene and the TP53 gene may be critical for the progression of a neurofibroma to a malignant schwannoma. The observations made are consistent with the concept of stepwise multigenetic changes in tumour progression. PMID- 8351252 TI - Adenosquamous carcinoma of the duodenum. An immunohistochemical study. AB - A rare adenosquamous carcinoma of the duodenum occurred in an 84-year-old woman. Histologically the neoplasm showed evidence of glandular and squamous differentiation, and both components showed malignant characteristics. Intermediate elements sharing squamous and glandular features, were found and were immunoreactive for carcinoembryonic antigen, epithelial membrane antigen and cytokeratins of both low and high molecular weight. A review of the literature and discussion about the histogenesis is included. PMID- 8351251 TI - Autoimmune oophoritis. An incidental finding. AB - A case of autoimmune oophoritis is reported. A 41-year-old woman had a total abdominal hysterectomy and bilateral salpingo-oophorectomy for menorrhagia, polymenorrhoea and cystic ovaries. The diagnosis of autoimmune oophoritis was not suspected clinically, and was an unexpected histological finding in the ovaries. The gross and histological appearances of this rare condition are described, and the lymphoid infiltrate characterised by immunocytochemistry. Recognition of this condition by pathologists is important, as there is an associated risk of developing other autoimmune disease, even some years later, necessitating close patient follow-up. In this case serum auto-antibodies to adrenal cortex were detected, indicating a subsequent risk of Addison's disease. PMID- 8351253 TI - Palpation thyroiditis resembling C cell hyperplasia. Usefulness of immunohistochemistry in their differential diagnosis. PMID- 8351254 TI - Audit of vitamin B12 therapy. PMID- 8351255 TI - Organophosphate pesticides--cause for concern? PMID- 8351256 TI - Recurrent pelvic inflammatory disease. PMID- 8351257 TI - Recurrent PID in general practice. PMID- 8351258 TI - Epilepsy. Establishing the diagnosis. PMID- 8351259 TI - Preparing for the CRQ and PEQ. PMID- 8351260 TI - Chronic heart failure. PMID- 8351261 TI - Preventing fractures. PMID- 8351262 TI - Degenerative musculoskeletal disease. PMID- 8351263 TI - Prescribing for older patients. PMID- 8351264 TI - Thyroid disease. PMID- 8351265 TI - Choosing an inhaler device. PMID- 8351266 TI - GPs are best placed to help people stop smoking. PMID- 8351267 TI - GPs should surrender some of their sovereignty. PMID- 8351268 TI - Unexplained fainting and breathlessness. PMID- 8351269 TI - Maxillary sinusitis. PMID- 8351270 TI - Helicobacter pylori eradication. PMID- 8351271 TI - The difficult patient. PMID- 8351272 TI - Epilepsy in practice. Management of a new case. PMID- 8351273 TI - Passing the MRCGP. The first oral examination. PMID- 8351274 TI - Blood disorders. PMID- 8351275 TI - Macrocytic anaemias. PMID- 8351276 TI - Microcytic anaemias. PMID- 8351277 TI - Sickle cell disease and thalassaemia. PMID- 8351278 TI - Haemophilia and haemorrhagic disorders. PMID- 8351279 TI - Polycythaemias. PMID- 8351281 TI - Eurotox '93. Uppsala, Sweden, June 30-July 3, 1993. Abstracts. PMID- 8351280 TI - Individualising HRT. PMID- 8351282 TI - Regulated expression of the major histocompatibility complex class I genes. AB - The major histocompatibility complex (MHC) class I gene products are known to play a fundamental role in foreign antigen presentation to the cellular immune system. Much attention has been directed to the study of MHC class I gene expression as a means to understanding the processes by which MHC class I mediated immune responses are regulated. Two areas of considerable interest have emerged, including regulation at the levels of transcriptional control and antigenic peptide-induced transport of MHC class I molecules. With an emphasis on these major areas of research, we review recent developments on the molecular and biochemical mediators and events of MHC class I gene regulation. PMID- 8351283 TI - Liver membrane composition after short-term parenteral nutrition with and without taurine in guinea pigs: the effect to taurine. AB - Having recently demonstrated that taurine supplementation prevents total parenteral nutrition (TPN)-induced cholestasis, we chose to use this model to examine plasma membrane composition in relation to bile formation. Male guinea pigs received daily a mixture of glucose and of the amino acid solution Travasol with or without added taurine (1.2 mM). After 3 days, bile was collected and liver plasma membrane fractions enriched in sinusoidal lateral membrane and bile canalicular membrane domains were isolated. In animals receiving TPN alone, bile flow and biliary secretory rate of bile acid and bicarbonate decreased significantly compared with controls. Although membrane ATPases (Na+K+ and Mg+) were unchanged, TPN induced an increase in the lipid to protein ratio and a decrease of polyunsaturated fatty acids, in conjunction with a higher content of diene conjugates in sinusoidal lateral membrane fractions. Taurine corrected these changes and, in addition, reduced significantly the cholesterol to phospholipid ratio in both membrane fractions. The data show that changes in liver cell membranes occur in TPN-induced cholestasis and suggest that free radical injury may play a role. As taurine prevented cholestasis as well as membrane changes, it is suggested that taurine should be added to amino acid solutions used for parenteral nutrition. PMID- 8351284 TI - Effects of cholera and pertussis toxins on prolactin stimulation of lactose synthesis and ornithine decarboxylase activity in mouse mammary gland explants. AB - Studies indicate that G proteins are likely involved in the signal transduction pathway for prolactin's stimulation of mitogenesis in Nb2 cells. In the mammary gland, little is known about the possible role of G proteins in the prolactin (PRL) stimulation of milk product synthesis. Therefore, the effects of cholera and pertussis toxin, enzymes that modify G protein activity, were tested on several actions of prolactin on mouse mammary tissue in culture. At concentration of 0.1-0.5 micrograms/ml, cholera toxin stimulated ornithine decarboxylase activity in a dose-response fashion; when tested in concert, cholera toxin and prolactin caused an additive response. Cholera toxin by itself did not affect the rate of lactose synthesis, but at concentrations above 0.5 micrograms/ml, it attenuated the magnitude of the prolactin stimulation of lactose synthesis. Pertussis toxin (0-0.5 micrograms/ml), both by itself and in concert with PRL, had no effect on ornithine decarboxylase activity. At concentrations of 25 ng/ml and above, pertussis toxin inhibited the PRL stimulation of lactose synthesis, whereas at 0.2 and 0.5 micrograms/ml, pertussis toxin abolished the PRL response. These observations suggest that a G protein, but not Gs, may be involved in prolactin's mechanism of signal transduction in the mouse mammary gland. PMID- 8351285 TI - Comparison of glucocorticoid-induced effects in prolactin-dependent and autonomous rat Nb2 lymphoma cells. AB - Cultured Nb2 node rat lymphoma cells require lactogenic hormone for their proliferation. We reported previously that dexamethasone (Dex) inhibits prolactin (PRL)-induced mitogenesis and, in the absence of mitogen, induces apoptosis of Nb2 cells. Both antiproliferative and cytolytic effects of Dex on Nb2 cells appear to involve glucocorticoid (Type II) receptor mediation. In this study, we compared Dex effects in PRL-dependent Nb2 cells (Nb2) with SFJCD1 (SF), a clone of Nb2 cells that proliferates independently of exogenous PRL. Proliferative assays involved a 72-hr incubation in a chemically defined, serum-free medium where ovine PRL (1 ng/ml) was added to Nb2 cells but not to SF cells. Both cell lines were responsive to the antiproliferative effects of Dex in a dose (6.25-200 nM)-dependent fashion of comparable sensitivity and magnitude. Co-incubation with the glucocorticoid receptor antagonist, RU 486, prevented the antiproliferative effect of Dex in both cell lines. In the same medium devoid of PRL, Dex was cytolytic to Nb2 cells and fragmented DNA in a fashion reflective of apoptosis, but was ineffective in SF cells. A dual chamber incubation system revealed no evidence that SF cells produced cytokines that were mitogenic or anticytolytic to Nb2 cells. Both Nb2 and SF cells fragmented DNA in a fashion indicative of apoptosis in the presence of the Ca2+ ionophore, A23187 (1 microM). These studies reveal a basic difference in glucocorticoid responsiveness between the PRL dependent Nb2 cell line and its PRL-independent subclone, SF. While both cell lines exhibit functional glucocorticoid receptors and the necessary intranuclear machinery for apoptosis, the pathway mediating the latter is inhibited or dysfunctional in SF cells. PMID- 8351286 TI - Maternal dietary zinc influences DNA strand break and 8-hydroxy-2'-deoxyguanosine levels in infant rhesus monkey liver. AB - Severe zinc deficiency in rodent models has been shown to influence the frequency of single-strand breaks in DNA isolated from liver. In the current study, we investigated whether DNA isolated from infant monkeys born to mothers fed zinc restricted diets would be characterized by higher than normal levels of DNA damage. DNA was isolated from 30-day-old infants born to dams fed low zinc (2 or 4 micrograms Zn/g) or control zinc (50 micrograms Zn/g) diets. The amount of single-strand breaks in liver DNA was significantly higher in the low zinc group than in controls; consistent with the above, there was a trend for higher steady state levels of liver 8-hydroxy-2'-deoxyguanosine in the low zinc group. While evidence for DNA damage in the low zinc group was obtained, the activities of several antioxidant enzymes were similar between the low zinc and control groups. In summary, infants born to monkeys fed low zinc diets are characterized by evidence of DNA damage shortly after birth; this damage may be due to an increased rate of oxidative damage and/or a reduction in the rate of DNA repair. PMID- 8351287 TI - Regulation of the angiotensinogen gene by estrogens in rat liver and different brain regions. AB - Estrogens regulate the production of angiotensinogen (AOG) in liver and other tissues. However, evidence suggests that the effect is tissue specific and that it may depend on a variety of factors. We have tested the effects of ethynylestradiol (EE) on liver AOG mRNA and plasma AOG in intact male and ovariectomized female rats, as well as in hypophysectomized male rats. EE stimulated both variables to a comparable extent and in a dose-dependent manner. However, its effect on plasma AOG was significantly higher in female than in male rats. In addition, there was no response in hypophysectomized male rats; however, responsiveness was restored by pretreatment of the animals with prolactin. AOG mRNA concentration was also affected by EE in brain, but there were striking time and region-specific differences. These results indicate that cell-specific factors also modulate the response of the AOG gene to EE in extrahepatic tissues. PMID- 8351288 TI - Low zinc status in rats impairs calcium uptake and aggregation of platelets stimulated by fluoride. AB - Platelets from rats of low zinc status exhibit impaired aggregation in response to ADP stimulation. The abnormality has been traced to defective uptake of calcium from the external medium. This study was designed to determine the location of the molecular defect and whether or not the ADP receptor is involved. Washed platelets were collected from rats fed a low zinc diet (< 1 mg/kg) and control groups that consumed a zinc-adequate diet (100 mg/kg), ad libitum- and pair-fed. Fluoride, a G-protein stimulant, was used to bypass the ADP receptor. F stimulated platelet aggregation and calcium uptake; both of these functions were impaired by zinc deficiency. At 10 mM F-, the time to half maximal aggregation was increased from 1.8 min in platelets from control to 2.8 min in zinc deficient rats. At 8 mM F-, the uptake of calcium was decreased from 170 to 85 nM cytosolic free calcium. At this concentration of F- there was no release of internal calcium. The results show that the molecular defect in the zinc-deficient platelet is located in the aggregation pathway beyond the ADP receptor and suggest a point between, or including, a G-protein and the plasma membrane calcium channel. PMID- 8351289 TI - Murine fetal development enhanced by dietary vitamin A, corn oil, and inositol. AB - Previous work on the effects of dietary vitamin A on craniofacial anomalies in mice revealed that 18-day-old fetuses from dams given 200 IU of vitamin A in corn oil daily in their diet weighed approximately 10% more than fetuses from mothers fed the unsupplemented standard mouse diet, Purina 5001. In the experiments reported here, it has been found that water-soluble vitamin A (200 IU/day) and myo-inositol (5 mg/day) added separately to the diets of pregnant mice increased the weight of 11-day gestations by approximately 25% and enhanced development of the eyes by the equivalent of 0.5-1.0 day without significantly affecting development of the liver or hind limbs. Corn oil alone (0.2 ml/day) had a similar effect on weight and eye development of 11-day fetuses and, in addition, growth of the hind limbs was enhanced modestly. The addition to the diet of vitamin A (200 IU/day) dissolved in corn oil (0.2 ml/day) resulted in a 25% increase in the weight of the 11-day fetuses and enhanced development of the eyes and hind limbs by the equivalent of about 1 day of gestation, suggesting that corn oil contains a factor(s) that interacts with vitamin A to accelerate limb development. Corn oil contains very small quantities of beta-carotene or retinol (< 1.0 IU vitamin A/ml); however, it is a rich source of the essential growth factors linoleic and linolenic acids and of inositol esters. The data suggest that the growth promoting actions of dietary corn oil are due in part to the inositol esters. PMID- 8351291 TI - Personal resourcefulness: positive aspects of functioning in high-risk research. AB - This paper discusses theoretical and measurement issues involved in attaining a differentiated picture of the distribution of outcomes in subjects selected for their elevated risk for psychosis; these outcomes include positive adaptations as well as subtle expressions of psychopathology. Many at-risk subjects either do not break down or actually "prosper" in the face of risk factors, a problem that persists even when risk groups are defined with increasing selectivity. Although this phenomenon is often referred to as the problem of "false positives" in risk research, its implications are more far-reaching than simply defining a problem of low yield in prospective studies. PMID- 8351290 TI - Muscarinic signaling pathway in submandibular cells of adult and early postnatal rats. AB - Elements of the muscarinic signal transduction pathway were compared in submandibular acinar cells of 1-day-old, 1-week-old, and adult rats after exposure to concentrations of acetylcholine ranging from 0.05 to 10 microM. Formation of inositol trisphosphate (IP3) and intracellular Ca2+ were comparable in cells from the three age groups after exposure to agonist concentrations < 1 microM. At higher agonist concentrations, IP3 generation and peak initial changes in [Ca2+]i were significantly greater in cells of newborn animals. In cells of 1 week-old animals, increased peak [Ca2+]i responses were seen even at low agonist concentrations, although IP3 production was not increased when compared with fully mature cells. Increased initial [Ca2+]i peaks, but comparable subsequent plateau [Ca2+]i values, were seen in the immature cells in both Ca(2+)-containing and Ca(2+)-free solutions. Permeabilized cells of early postnatal animals took up less 45Ca2+ into nonmitochondrial Ca2+ pools in the presence of 1.5 mM ATP and also released less tracer in response to intermediate IP3 concentrations than adult cells. Developing salivary cells thus show differences in important functional linkages of the muscarinic signal transduction pathway, including those between receptor activation and phosphoinositide turnover and between IP3 and release of internally stored Ca2+. Differences in the Ca2+ stores or in their sensitivity to IP3 may account for the latter observation. Immature salivary cells seem to have adequate mechanisms for Ca2+ entry. PMID- 8351292 TI - Adult children of alcoholics: narcissism, shame, and the differential effects of paternal and maternal alcoholism. AB - Recent clinical and research literature has suggested that having one or both parents alcoholic leads to higher levels of character pathology (Baker and Williamson 1989; Benson and Heller 1987; Berkowitz and Perkins 1988; Brown 1988; Hibbard 1987, 1989; Parker and Harford 1988; Plescia-Pikus et al. 1988; Soyster 1984; Wood 1987) than is normal for nonclinical adults. Only Berkowitz and Perkins (1988) have looked at what difference it may make as to which parent is identified as alcoholic. PMID- 8351293 TI - The long reach of violence and aggression. AB - The immediately preceding issue of psychiatry focused on the effects of violence on children. Of particular concern was the immediate impact of violence in the community on psychiatric symptoms in young children. Also of concern was the relationship of community violence to violence and abuse of children in the home, and the short-term impact of violence on many facets of child development. A group of five papers in the current issue focuses on the long-term impact of violence, aggression, and trauma; its impact on development into late adolescence and on severe character pathology in adulthood. Also of concern in this section are some of the origins of violence and abusive behavior toward children. PMID- 8351294 TI - Toward a model of family and political victimization: implications for treatment and recovery. AB - Political violence, in any of its ugly guises, has a devastating and long-lasting effect on its victims. This effect derives, in my view, from the concurrence of two factors: (1) the physical and emotional violence is perpetrated by the very agencies of society (such as the police and the armed forces) entrusted with the care and protection of individuals, with maintaining order in their world, with enforcing stability, and predictability; and (2) a context or a discourse that destroys or mystifies meanings so that recognition of that shift from protection to violence is blurred. PMID- 8351295 TI - A critique of conceptual and treatment approaches to borderline psychopathology in light of findings about childhood abuse. AB - A series of recent research findings has begung to supply strong evidence of a highly significant correlation between borderline psychopathology and experiences of repeated childhood trauma including sexual abuse (especially incest), physical abuse, and the witnessing of severe domestic violence (Bryer et al. 1987; Herman et al. 1989; Western et al. 1990; Zanarini et al. 1989). The replication of these results with different research samples is in contrast to the inconsistent findings associated with earlier etiological theories, in which the roots of borderline pathology were variously linked to schizophrenic or affective illnesses (Akiskal 1981; Akiskal et al. 1985; Klein 1977; Perry 1985), to derailments in the separation-individuation process (Kernberg 1975, 1976; Mahler and Kaplan 1977; Masterson and Rinsley 1975), to actual early losses and separations (Bradley 1979; Paris et al. 1988; Soloff and Millward 1983a, 1983b), to severe empathic failures during the first years of life (Adler and Buie 1979), or to more general family-based pathologies (Frank and Hoffman 1980; Frank and Paris 1981; Grinker et al. 1968; Gunderson and Englund 1981; Gunderson et al. 1980; Links 1990; Walsh 1977; Zinner and Shapiro 1975). Not only do current findings regularly identify 50% to 80% of subjects as victims of childhood abuse and trauma, but also several studies show that factors such as age of onset, severity, and type of abuse reliably discriminate between borderline and other diagnostic groups (Herman et al. 1989; Zanarini et al. 1989). PMID- 8351296 TI - Sexual abuse and psychopathology. AB - With the recognition that sexual exploitation of children is far more common than previously thought, a substantial research effort has aimed to describe its acute and long-term effects (Kluft 1990). Most studies have been quantitative and have pursued one of two strategies: Children identified by referral from child protective services as physically victimized are concurrently assessed for psychiatric sequelae; alternatively, adults with or without various psychiatric syndromes are retrospectively asked to recall the presence or absence of traumatic childhood experiences. Descriptive in focus, the results of these research efforts have broadened our understanding of the typical constellation of symptoms experienced by childhood incest victims and have delineated the adult psychiatric diagnostic categories most associated with a history of childhood trauma. PMID- 8351297 TI - [The prognostic significance of the therapeutic working alliance from the perspective of the patient and therapist]. AB - In general, the prognostic relevance of a working alliance for both the course and the outcome of psychotherapy is no longer a matter of dispute. Since a working alliance is conceived as an interactional variable, the results must be interpreted on the basis of several important dimensions: the perspective of the investigator and the time structure during the course of therapy. Using the data available from the Berlin Psychotherapy Study (Rudolf 1991), we investigated for the 238 patients (inpatients and outpatients who received psychoanalytically oriented therapy in the study) the prognostic relevance of diagnostic and therapy related working alliance variables for the various outcomes investigated. A complex correlation-statistical method (latent-trait-model) was used to consider the investigator perspective with regard to the working alliance and the outcome as well as the time structure and the diagnostic variables. Our results emphasize the relevance of the therapist's perspective beginning with the diagnostic indication, the working alliance and finally the outcome. The patient's perspective, however, seems to be less relevant. The results are presented and discussed in relation to the relevant literature. One result we have found as a further important dimension is that the kind of therapy carried out must be taken into consideration. This implies that as in our study for all phases of the investigation therapy specific instruments must be applied. In this regard our results also contribute to the validation of the instrument used to measure the working alliance TAB. PMID- 8351298 TI - [The significance of the Balint-group work: a review of the literature and an empirical study in Unterfranken]. AB - The group work initiated by Michael Balint aims at a comprehensive understanding of the doctor-patient-relationship and a patient-centered medicine. In a review of the literature some studies are presented, which focus on results of Balint work and changes in the participants of this group method. An empirical study of 436 physicians in Unterfranken shows that about 9% have participated in Balint work. Attitudes and motivations of the participants and setting and results of Balint work are studied as well as notions and knowledge of those, who have not done Balint work yet. The study demonstrates positive results in most of the participants. PMID- 8351300 TI - [DKPM basic documentation. A uniform basic documentation for inpatient psychosomatic treatment and psychotherapy]. AB - The Arbeitsgemeinschaft Basisdokumentation presents the DKPM-Basisdokumentation, which is conceptualized as a uniform modul of a documentation system for the routine-like use in the in-patient psychosomatic and psychotherapy. We outline possibilities of use, aspects of the data security and the data access as well as some practical presuppositions. PMID- 8351299 TI - [Is there a typical conflict in dyspepsia? An epidemiologic psychoanalytic contribution to the topic of a specific conflict in psychosomatic medicine]. AB - The question whether a dependency-independency-conflict is specific for subjects with gastric complaints was investigated by means of a representative, psychoanalytic-epidemiologic field study (Mannheimer Kohortenprojekt). Out of a population of 600 adults probands with dyspepsia were compared with individuals with musculoskeletal symptoms and "healthy" subjects. Using interview protocols of these individuals two "blinded" raters judged whether the conflict under consideration was present in different aspects of life. It could be confirmed that subjects with gastric complaints showed the conflict significantly more often than either control group. However, the conflict was also found among individuals of either control group. It can be concluded that the dependency independency-conflict is typical, but not specific for subjects suffering from dyspepsia. PMID- 8351301 TI - [The status of psychotherapy with handicapped patients]. AB - Psychotherapy for the handicapped might play an important role in helping these multiply stressed persons and their families. It can be put into practice much more easily than one may have presumed. It does not require any extreme specializations. Therefore, the gap between what is possible and the actual reality of a deep lack of efforts in this field calls for explanations, a part of which the author tries to outline. PMID- 8351302 TI - Robert Kellner, M.D., Ph.D., 1922-1992. PMID- 8351303 TI - Psychopharmacologic issues in organ transplantation. Part 2: Psychopharmacologic medications. AB - This article reviews psychopharmacology in organ transplant patients, with particular attention to the changes in the metabolism and elimination of drugs during organ insufficiency and drug interactions in the immunosuppressed state. The side effects of psychotropic drugs need to be distinguished from those of immunosuppressants. Antidepressants, including tricyclics, heterocyclics, MAOIs, stimulants, and newer agents, are discussed. Use of neuroleptics for delirium, mania, and other organic disorders is described. Lithium may be more difficult to use in the immediate postoperative period. Anxiolytics, including benzodiazepines and buspirone, are useful depending on the underlying medical problem. PMID- 8351304 TI - A literature review of psychotic symptoms associated with the premenstruum. AB - The proposed DSM-III-R diagnostic category, Late Luteal Phase Dysphoric Disorder (LLPDD), is a severe form of premenstrual disturbance. Core symptoms include mood lability and dysphoria with no psychotic features. Yet transient psychotic symptoms during the late luteal phase and during menstruation have been noted in the literature for decades. Although good prospective data are lacking, patients with these disturbances may variably be subsumed under diagnostic categories of "atypical psychosis," "periodic psychosis," and "cycloid psychosis." In this article, several patients displaying premenstrual psychoses are described. A review of the literature on psychoses during the menstrual cycle as it relates to the diagnostic criteria for LLPDD follows. PMID- 8351305 TI - The sequencing of psychiatric recommendations. Concordance during the process of a psychiatric consultation. AB - Whether or not medical staff follow through with the recommendations of the consultation-liaison (C-L) psychiatrist, a process referred to as concordance, is an important factor that influences the outcome of C-L interventions. Previous research has demonstrated that process variables have the greatest effect on concordance. This study extends earlier research by examining the relationship of the timing of various recommendation types and concordance. In this study, the authors found that during the first two weeks of a case, psychosocial diagnostic recommendations were closely followed (most concordant) when given later in the consultation. However, concordance was better when discharge recommendations were given earlier. The findings reveal an interaction between the type of recommendation and its timing in the consultation in predicting concordance. PMID- 8351306 TI - Psychosocial evaluation of organ transplant candidates. A comparative survey of process, criteria, and outcomes in heart, liver, and kidney transplantation. AB - Psychosocial selection criteria are widely used by transplant programs but have not been systematically described or compared within or across transplantation type. The authors surveyed all active cardiac, liver, and renal transplant programs in the United States about the existence of psychosocial selection criteria, how and by whom patients were evaluated, weight given to specific criteria, and how often patients were rejected for surgery on psychosocial grounds. The results document important differences in the process, criteria, and outcomes of pretransplant psychosocial evaluation within and across these programs. Cardiac programs are the most stringent, both in criteria and in rate of refusals. PMID- 8351307 TI - Rapid relief of anxiety in cancer patients with both alprazolam and placebo. AB - This study evaluated 36 cancer patients who were enrolled in a randomized, double blind, placebo-controlled trial conducted over a 4-week period to evaluate the efficacy of alprazolam in the treatment of anxiety associated with cancer. Hamilton Anxiety Scale scores declined significantly between baseline and the end of the first week of the study in both treatment groups. There was no significant difference in response between the patients receiving alprazolam and placebo. Similar results were obtained from other instruments. These results suggest that nondrug factors or spontaneous improvement may play a more important role than pharmacotherapy in the treatment of anxiety associated with cancer. PMID- 8351308 TI - Etiology and clinical course of pseudoseizures. Relationship to trauma, depression, and dissociation. AB - Twenty-seven outpatients with video-EEG-documented pseudoseizures were interviewed by a psychiatrist to determine the historical course of seizures and diagnose the current presence of these DSM-III-R diagnoses: affective disorders (85%), dissociative disorders (85%), and posttraumatic stress disorder (33%). Their mean (26.7) and median (26.9) Dissociative Experiences Scale scores were elevated. Eighty-eight percent of subjects had sustained significant trauma, including sexual abuse/rape (77%) and physical abuse (70%). Four psychodynamic pathways to pseudoseizures were noted. Most commonly, pseudoseizures originated from dissociated personalities or ego states, were expressions of dissociated memories of child abuse, and were triggered by recent stresses or traumas. PMID- 8351309 TI - Some advantages of consultation-liaison (medical-surgical) psychiatry becoming an added qualification subspecialty. PMID- 8351310 TI - Are thymoleptic-responsive "anger attacks" a discrete clinical syndrome? PMID- 8351311 TI - Do some chronic pain patients with atypical facial pain overvalue and obsess about their pain? PMID- 8351312 TI - A case report of Munchausen syndrome with mixed psychological features. PMID- 8351314 TI - Aseptic meningitis associated with salicylate overdose. PMID- 8351313 TI - Late-onset depression with white matter lesions. PMID- 8351315 TI - Breast hypoplasia as an initiating factor in anorexia nervosa. PMID- 8351316 TI - Coexistent hypomania and severe hypothyroidism. PMID- 8351317 TI - MR imaging of the pancreas. AB - Magnetic resonance (MR) imaging sequences that reduce image artifact in upper abdominal examinations herald a role for MR in the investigation of pancreatic disease. Sequences that have been successful in imaging the pancreas are T1 weighted breath-hold gradient-echo imaging, which avoids phase artifact caused by respiration, and T1-weighted fat-suppressed spin-echo imaging, which reduces breathing artifact, removes chemical shift artifact, and improves dynamic range of signal intensities. Breath-hold gradient-echo sequences provide useful diagnostic information when used prior to and immediately following bolus intravenous administration of gadopentetate dimeglumine. This review addresses current clinically important roles for MR imaging and emphasizes the detection of islet cell tumors, non-organ-deforming pancreatic ductal adenocarcinomas, and the distinction between chronic pancreatitis and cancer. PMID- 8351318 TI - Imaging of the shoulder. PMID- 8351319 TI - Complications of vena cava filters. PMID- 8351320 TI - Ligament and tendon tears: secondary signs. PMID- 8351321 TI - No fooling around: direct visualization of pulmonary embolism. PMID- 8351322 TI - Acute interstitial pneumonia: histopathologic patterns of acute lung injury and the Hamman-Rich syndrome revisited. PMID- 8351323 TI - It's academic. PMID- 8351325 TI - Idiopathic hemochromatosis: MR imaging findings in cirrhotic and precirrhotic patients. AB - The authors reviewed T2-weighted and T2*-weighted abdominal magnetic resonance (MR) images in 19 pathology-proved cases of hepatic iron overload to compare patterns of iron distribution among cirrhotic and precirrhotic patients with idiopathic hemochromatosis (IH), as well as nontransfusional hepatic siderosis of other causes. Fifteen patients had clinical and laboratory evidence of IH. Four patients without IH had cirrhosis with moderate siderosis. In the MR images of all 19 patients, the liver had low signal intensity. The pancreas of 10 of 11 cirrhotic patients with IH had low signal intensity. All four precirrhotic patients with IH and all four cirrhotic patients without IH had pancreas with normal signal intensity at MR. Thus, pancreatic signal intensity was decreased only in cirrhotic patients with IH in this limited series. Conversely, pancreatic signal intensity is often normal in precirrhotic patients with IH prior to the development of cirrhosis, a stage at which definitive diagnosis by means of quantitative liver biopsy is important because early phlebotomy may prevent morbidity and mortality from IH. In cirrhotic patients with MR evidence of increased hepatic iron, the cause of cirrhosis is less likely to be IH if pancreatic signal intensity is normal. PMID- 8351324 TI - Hepatic CT enhancement: a method to demonstrate reproducibility. AB - Optimal techniques for intravenous administration of contrast material in computed tomographic (CT) examination of the liver remain controversial mainly because of inaccurate methods of data evaluation. This study tested the reproducibility of hepatic contrast material enhancement within the same patient and the accuracy of two methods of data analysis. Fourteen patients received identical CT examinations. Attenuation of liver and vessels was measured before and after administration of contrast material, and enhancement was calculated for each image. Data were analyzed by averaging enhancement values obtained over 5- and 10-second intervals and by using a new computer program that creates an enhancement-time curve and measures area under the curve (AUC) for any specific time interval. Data were compared between patients' first and second examinations. Mean liver enhancement was nearly identical at all time intervals with the AUC technique. Analysis of interpatient data showed marked variability of all parameters at all measured time intervals, suggesting that results from comparative studies within the same patient may be more accurate than those for studies of two different treatment groups. The AUC technique is preferable to other methods of data analysis for contrast enhancement evaluation. PMID- 8351326 TI - Evaluation of portal venous hypertension with cine phase-contrast MR flow measurements: high association of hyperdynamic portal flow with variceal hemorrhage. AB - Thirty-two patients with portal venous hypertension and endoscopically proved esophageal varices who were being evaluated for possible liver transplantation were studied with cine phase-contrast magnetic resonance (MR) imaging. Flow measurements in the main portal vein were obtained and associated with the presence of variceal hemorrhage within 2 years before the MR examination. Low (hypodynamic) flow was present in 22 patients, while high (hyperdynamic) flow was present in 10 patients. The presence of variceal hemorrhage was significantly associated with a high portal venous flow rate (P = .001), high variceal grade (P = .030), and Child class A or B (P = .003); however, only portal venous flow (P = .006) and variceal grade (P = .044) were found to be associated with variceal hemorrhage in a multiple logistic regression analysis. The portal venous flow rate was significantly higher among patients with Child class A or B disease compared with those with class C disease (median, 24.6 vs 8.0 mL/min.kg; P = .004). PMID- 8351327 TI - Small bowel obstruction: sonographic evaluation. AB - Results of 54 sonographic examinations of patients referred for suspected or known small intestinal obstruction were retrospectively correlated with surgical findings, and the diagnostic value of sonography regarding presence, level, and cause of obstruction was compared with that of plain abdominal radiography. The diagnosis of obstruction was correct in 89% of cases with sonography and in 71% with plain radiography. The level of obstruction was correctly predicted in 76% of cases with sonography and in 51% with plain radiography. The cause of obstruction was correctly predicted in 20% of cases with sonography and in 2% with plain radiography. The authors conclude that use of sonography in evaluating patients with bowel obstruction may be helpful in confirmation of the presence of obstruction, in determination of the level of obstruction, and in identification of the cause of obstruction. PMID- 8351328 TI - Posterior tibial tendon tears: utility of secondary signs for MR imaging diagnosis. AB - To assess the range of appearance of both torn and normal posterior tibial tendons (PTTs) and to evaluate secondary signs related to abnormal biomechanics as aids in diagnosing PTT tears, 23 patients with complete PTT tears and 34 control patients were examined with magnetic resonance imaging at 1.5 T. Examiners were blinded to diagnosis. The diameter of the PTT was measured at the insertion and at the level of the ankle. The torn and control PTTs were bulbous distally (respective mean values, 6.2 mm vs 4.6 mm), with overlap in the range of tendon size. All PTTs also had overlap in the frequency of intra-tendon signal intensity (torn PTTs, 83%, vs control PTTs, 41%; T1-weighted, 61%, vs T2 weighted, 22%). The presence of a talonavicular abnormality was both a sensitive (82%) and specific (100%) sign of a PTT tear. The presence of medial tubercle hypertrophy (sensitivity, 89%; specificity, 75%) and an accessory navicular bone (sensitivity, 20%; specificity, 100%) were useful secondary signs of a complete PTT tear. PMID- 8351329 TI - Tears of the anterior cruciate ligament: primary and secondary signs at MR imaging. AB - To investigate primary and secondary signs of anterior cruciate ligament (ACL) tear at magnetic resonance (MR) imaging, the authors retrospectively reviewed 103 MR imaging examinations obtained in 99 patients, the original interpretations of these examinations, clinical records, and arthroscopy reports. Fifty cases of arthroscopy-documented complete ACL tear were included. The primary signs of ACL tear (ie, abnormal ACL morphologic features or signal intensity) had respective sensitivity and specificity values of 96% (48 of 50 examinations) and 94% (50 of 53) on sagittal images and 92% (46 of 50) and 83% (43 of 52) on coronal images. As a secondary sign of ACL tear, bone bruise involving the lateral compartment of the knee was found in 40% (20 of 50) of cases of ACL tear and in 4% (2 of 53) of cases of normal ACL. The mean curvature of the posterior cruciate ligament was increased (0.40 vs 0.27; P < .0001) in cases of ACL tear. An abnormal appearance of the ACL on sagittal images remains the single most sensitive and specific sign of ACL tear. PMID- 8351331 TI - Quadrilateral space syndrome: findings at MR imaging. AB - Shoulder pain due to compression of the axillary nerve by fibrous bands in the quadrilateral space has been termed the quadrilateral space syndrome. Selective atrophy of the teres minor muscle, which is innervated by the axillary nerve, was demonstrated at magnetic resonance imaging in three patients with clinical findings of the syndrome. This finding, in the appropriate clinical setting, is highly suggestive of the quadrilateral space syndrome, which is a potentially reversible cause of shoulder pain. PMID- 8351330 TI - Waldenstrom macroglobulinemia: MR imaging of the spine and CT of the abdomen and pelvis. AB - Twenty-three consecutive patients with Waldenstrom macroglobulinemia were studied with magnetic resonance (MR) imaging of the spine and computed tomography (CT) of the abdomen and pelvis. MR imaging studies included sagittal T1-weighted and gradient-recalled-echo sequences performed with and without contrast material enhancement. Marrow involvement was identified with MR imaging in 21 of 23 (91%) patients. Diffuse involvement was noted in 13 patients (56%), and a variegated pattern in eight (35%). CT demonstrated enlarged nodes in 10 of 23 (43%) patients. Correlation of MR imaging patterns and presence of adenopathy at CT with standard laboratory values for Waldenstrom macroglobulinemia revealed an association of the diffuse MR imaging pattern of marrow involvement and the presence of enlarged nodes at CT with more advanced disease. MR imaging of the spine and CT are reliable means of evaluation of disease status in Waldenstrom macroglobulinemia. They may be employed as additional means in the staging of Waldenstrom macroglobulinemia and may be helpful in the follow-up of patients with this rare hematologic malignancy. PMID- 8351332 TI - Direct coronal view of the shoulder with arthrographic CT. AB - Direct coronal oblique views of the shoulder were obtained with arthrographic computed tomography (CT) in 35 shoulders with surgical correlation. There were 18 complete cuff tears, four partial ones, two type 3 superior labral, anterior, and posterior (SLAP) lesions, and one type 4 SLAP lesion. The coronal sections were obtained after double-contrast shoulder arthrography and axial CT sections had already been obtained. The patient was seated directly on the slope of the gantry, and the shoulder to be studied was positioned in the center of the gantry. The maximal time needed for this procedure was 5 minutes. Rotator cuff tears were detected with a sensitivity of 95% and a specificity of 100%. The size of the tears as determined on the coronal sections was strongly correlated with surgical measurement (r = .939). All SLAP lesions were detected. The authors' experience shows that obtaining coronal oblique sections is an effective way to improve arthrographic CT. PMID- 8351333 TI - Rotator cuff: evaluation with fat-suppressed MR arthrography. AB - Thirty-seven shoulders with rotator cuff diagnoses proved at arthrography, arthroscopy, or open surgery were examined prospectively with magnetic resonance (MR) arthrography. T1-weighted MR images were obtained with and without fat suppression after intraarticular injection of gadopentetate dimeglumine. Without fat suppression, overall accuracy was 84%. False-positive full-thickness tears were diagnosed in three patients who were proved to have partial tears. False negative normal tendons were diagnosed in two patients who had partial tears. The corresponding sensitivity and specificity were 90% and 75%, respectively. With the aid of fat-suppressed imaging, full-thickness and partial cuff tears were identified with 100% sensitivity and specificity. Fat-suppressed images also showed intratendinous contrast material imbibition in three torn cuffs with frayed, friable tendon margins. Fat suppression in MR arthrography is valuable in the differentiation of partial from full-thickness cuff tears and in the detection of small partial tears of the inferior tendon surface. PMID- 8351334 TI - Hematopoietic bone marrow within the proximal humeral epiphysis in normal adults: investigation with MR imaging. AB - The occurrence of hematopoietic bone marrow within the axial skeleton and meta diaphyseal regions of long bones is well known. However, it has been generally accepted that hematopoietic marrow is not present within the epiphysis of long bones in normal adults. This study involved evaluation of marrow patterns in 96 patients presenting for shoulder magnetic resonance (MR) imaging examinations. Residual hematopoietic marrow was present within the proximal humeral metaphysis in 99% of patients and extended into the epiphysis in 62%. Epiphyseal hematopoietic marrow was more prominent in female subjects (P = .015) and showed correlation with prominence of hematopoietic marrow within the proximal humeral metaphysis (P = .01). The most characteristic pattern was a curvilinear distribution of hematopoietic marrow involving the subcortical region of the medial humeral head, though in some patients more centrally located patchy or globular regions of hematopoietic marrow were observed. These findings indicate that when signal intensity variations are observed within the epiphysis on MR images, the possibility of residual or reconverted hematopoietic marrow should be considered. PMID- 8351335 TI - Facial lymph nodes: normal and abnormal CT appearance. AB - Facial lymph node involvement by neoplastic disease is an unusual occurrence. The purpose of this study was to determine the normal and abnormal radiologic appearance of the facial nodes. Two hundred enhanced computed tomographic (CT) studies of patients not at risk for facial node metastasis were studied prospectively to establish a normal control group. One hundred consecutive patients with extensive recurrent or primary cancer of the epidermal structures of the face, the sinonasal region or deep face, or the mucosal surface of the oral cavity were examined prospectively to establish a prevalence for metastatic facial adenopathy. In addition, all cases of facial node metastases seen on imaging studies over an 11-year period (n = 21) were examined retrospectively to establish the spectrum of facial lymphadenopathy. Normal nodes could not be confidently identified on CT studies. When nodal metastasis occurred, it was often in the setting of recurrent disease. The infraorbital nodes tended to be the site of origin for lymphomas isolated to the canine fossa. PMID- 8351336 TI - Internal architecture of the parotid gland at MR imaging: facial nerve or ductal system? AB - A radiologic-anatomic study was performed to determine the nature of the low signal-intensity curvilinear structures currently seen in the normal parotid gland on axial T1-weighted magnetic resonance (MR) images. These structures are considered by some to represent the intraparotid facial nerve. After cannulation of the Stensen duct, the authors imaged the parotid gland of two cadavers in situ before and after intraductal injection of gadolinium tetrazacyclododecanetetraacetic acid. Retrograde filling was obtained in one gland. The same sections were used throughout a subsequent anatomic study, allowing correlation of the MR findings with the macroscopic and histologic appearance of the gland. Comparison of MR images and gross and histologic sections established that two intraparotid facial nerve segments, although identified from the histologic study, were not visible on corresponding MR images. Many areas of low signal intensity seen within the gland were found to represent the main duct and some afferent ductal branches. PMID- 8351337 TI - CT-guided injection of the stellate ganglion: description of technique and efficacy of sympathetic blockade. AB - Stellate ganglion blockade, typically performed by using palpable osseous landmarks, is an accepted method in the diagnosis and treatment of sympathetically maintained pain and other conditions. The authors present the results of stellate ganglion injection performed with computed tomographic (CT) guidance. Thirteen CT-guided procedures were performed in seven patients. Lidocaine, bupivacaine, and buprenorphine were used to achieve the blockade. Successful blocks were achieved in all 13 cases as evidenced by production of Horner syndrome and ipsilateral hand temperature elevations. The average ipsilateral and contralateral hand temperature changes following the procedure were 7.5 degrees C and 0.5 degrees C. The ipsilateral hand temperature changes and the differences between the ipsilateral and contralateral hand temperature changes exceeded 1.5 degrees C in every case. Five patients preferred the CT guided procedure over the conventional technique, and two patients noted no substantial difference between the approaches. With the CT-guided technique, a highly effective sympathetic block is achieved with a substantially reduced volume of anesthetic compared with the conventional approach. PMID- 8351338 TI - Echo-planar perfusion-sensitive MR imaging of acute cerebral ischemia. AB - T2*-sensitive echo-planar magnetic resonance imaging was used with first-pass magnetic susceptibility contrast enhancement in a cat model of acute regional stroke to evaluate the relationship between cerebral hypoperfusion and ischemic brain damage. In normal brain, dose-dependent decreases in signal intensity were observed after intravenous injection of 0.15-0.50 mmol/kg dysprosium diethylenetriaminepentaacetic acid bismethylamide or gadodiamide injection. Shortly after unilateral occlusion of the middle cerebral artery, foci of signal hyperintensity on diffusion-weighted images were observed in the ipsilateral basal ganglia. Sixty minutes after occlusion, perfusion deficits in the ipsilateral parietal and temporal cortical gray matter were observed to be spatially correlated with areas of hyperintensity on diffusion-weighted images. When reflow was attempted after 60 minutes, delayed contrast agent transit suggestive of partial ischemic tissue injury was demonstrated. Attempts to produce reflow after 2 hours did not restore normal brain perfusion and resulted in image hyperintensity and histopathologic brain damage. Six-hour occlusion was associated with pronounced perfusion deficits in the ischemic territory. PMID- 8351339 TI - Human brain: proton diffusion MR spectroscopy. AB - Diffusion of brain metabolites was measured in 10 healthy volunteers by using localized proton diffusion magnetic resonance (MR) spectroscopy. Measurements were conducted with a clinical MR imager by using a stimulated-echo pulse sequence (3,000/60 [repetition time msec/echo time msec], 200-msec mixing time) with additional outside-volume suppression. Motion artifacts due to macroscopic brain movements were compensated by means of peripheral cardiac gating and separate collection of individual spectroscopic acquisitions into a two dimensional data matrix. Phase errors due to macroscopic motion were subsequently corrected in individual data traces prior to spectral averaging. Mean (+/- 1 standard deviation) apparent diffusion coefficients of choline-containing compounds ([0.13 +/- 0.03] x 10(-3) mm2/sec), creatine and phosphocreatine ([0.15 +/- 0.03] x 10(-3) mm2/sec), and N-acetyl aspartate ([0.18 +/- 0.02] x 10(-3) mm2/sec) were substantially smaller than that of water and were consistent with recently published data obtained in anesthetized and paralyzed animals. Adequate diffusion sensitivity for metabolites in the human brain can be obtained with clinical whole-body imagers despite macroscopic head and brain movements. PMID- 8351340 TI - Asymptomatic and neurologically symptomatic HIV-seropositive subjects: results of long-term MR imaging and clinical follow-up. AB - Cranial magnetic resonance (MR) images were prospectively obtained in 74 human immunodeficiency virus (HIV)-seropositive subjects, all of whom had undergone MR imaging 24-42 months earlier. The images were interpreted by neuroradiologists blinded to the subject's clinical status and were compared with the initial MR images and clinical findings. Ten subjects had mild neurologic symptoms, with mildly abnormal unchanged images in five (50%). Sixty-four subjects were neurologically asymptomatic, with mildly abnormal images in 13 (20%), most of which remained unchanged. chi 2 analysis revealed a significant difference (P = .042) between the asymptomatic and symptomatic groups with regard to the number of subjects with abnormal follow-up images. The number of abnormal images in the asymptomatic subjects was significantly less than that in the symptomatic subjects. During follow-up of 2-3 1/2 years, most asymptomatic subjects had persistently normal MR images. When abnormal, the imaging abnormalities were usually static and minor. PMID- 8351341 TI - Frameless stereotaxic integration of CT imaging data: accuracy and initial applications. AB - To evaluate the spatial accuracy of a rapid interactive method of transferring computed tomographic (CT) information between its display on a computer screen to its source (test object, operating field), a multidimensional computer combined with a six-jointed position-sensing mechanical arm was tested with a Plexiglas model consisting of 50 rods of varied height and known location, a plastic replica of the skull, and, subsequently, three patients. The median error value between image and real location was 1-2 mm (P > .95), regardless of the registration target sites. The accuracy, however, increased with the selection of widespread registration points, and 95% of all errors were below 3.70 mm (P > .95). The results compare favorably with the four most commonly used stereotaxic framed units. A misregistration error of 0.3-2.2 mm was found during intraoperative correlation between anatomy on the CT display and actual anatomic location in the operative field. PMID- 8351342 TI - Hippocampal sulcus remnant: potential cause of change in signal intensity in the hippocampus. AB - A small area of changed signal intensity in the hippocampus is often seen on magnetic resonance (MR) images of the brain in patients without specific clinical signs or symptoms. To ascertain its cause by means of histologic examination, this finding was evaluated retrospectively in 109 patients and correlated with findings in two human brain specimens. This area of change was typically round or curvilinear and 1-2 mm in diameter. Its location was between the hippocampus and dentate gyrus. The signal intensity was the same as that of cerebrospinal fluid (CSF) with all MR sequences used. The incidence of change in signal intensity was greater in elderly patients. Correlation with histologic findings showed that this area of change, a dilated perivascular space, was the residual cavity of the hippocampal sulcus. Whenever an area of CSF-like signal intensity has this shape and topographic features, the possibility of anatomic variation should be considered before the change in signal intensity is diagnosed as brain injury. PMID- 8351343 TI - Dural invasion by craniofacial and calvarial neoplasms: MR imaging and histopathologic evaluation. AB - The authors prospectively correlated results of magnetic resonance (MR) imaging and histologic examination of the dura in 17 patients with craniofacial and calvarial neoplasms and possible intracranial extension. Contrast material enhanced MR imaging revealed dural enhancement in 14 patients and no enhancement in three. In four cases, the dura deep to the tumor appeared as a continuous band of enhancement and there was a thin unbroken hypointense zone between the dura and the tumor. Histologic examination in these four patients revealed only dural inflammation without neoplastic spread. In 10 patients, there was a break in the continuity of the enhancement of the underlying dura or a portion of the dura and overlying enhancing tumor could not be separated on MR images. The hypointense zone was focally absent in nine of these cases, and in all 10 there was invasion of the dura by adjacent tumor. Among the other three patients, in whom dural enhancement was not discernible, one had dural invasion by tumor while the other two did not. PMID- 8351345 TI - Prenatal growth of the human cerebral cortex: brainprint analysis. AB - To construct a series of flat maps (brainprints) that document the prenatal growth of human cerebral cortex and help identify sulcal landmarks for division of cortical regions of interest (ROIs) on mapped surfaces, the authors photographed and traced histologic whole-brain slices of 25 normal human fetal brains aged 18-42 weeks gestation. Brainprints of both cerebral hemispheres from each fetus were constructed with semiautomatic brain-mapping software, and each map was divided into five ROIs based on sulcal landmarks: frontal, parietal, insular, occipital, and temporal cortices. Surface areas of cerebral hemispheres and the five ROIs were estimated. Corrected for histologic shrinkage, brainprint estimates of human fetal cortical surface area were approximately twice those of previous estimates. Cortical lobe proportions at 18 weeks appeared to be unchanged to term. Surface area estimates correlated with fetal age, brain weight, and brain volume. This collection of cortical maps may guide future quantitative analyses of cerebral hemispheric growth in premature and term infants who undergo magnetic resonance imaging, which may, in turn, help predict neurobehavioral outcomes of early cortical damage. PMID- 8351344 TI - Cerebral sparganosis: MR imaging versus CT features. AB - Fourteen magnetic resonance (MR) images of 11 patients with cerebral sparganosis were reviewed retrospectively and compared with 13 computed tomographic (CT) scans of 10 of the patients. All patients underwent both nonenhanced and contrast material-enhanced MR imaging. All white matter degenerations, which were slightly hypointense on T1-weighted images and were hyperintense on T2-weighted images, were seen as areas of low attenuation on CT scans. Better contrast between normal and degenerated brain tissues was seen at MR, and two lesions were seen that were missed at CT. The parasitic granuloma was isointense to brain parenchyma on images obtained with all pulse sequences. On two follow-up MR images, location or shape of the enhancing lesions changed, suggesting migration of the worm. A new finding of hyperintensity on T1-weighted images and hypointensity on T2-weighted images in subcortical areas probably due to petechial hemorrhages was demonstrated in eight patients only at MR. Small calcific foci, which were important diagnostic clues of cerebral sparganosis, were detected in four patients only at MR, while they were seen in eight patients at CT. PMID- 8351346 TI - Thoracic cardiovascular anomalies in children: evaluation with a fast gradient recalled-echo sequence with cardiac-triggered segmented acquisition. AB - A fast gradient-recalled-echo sequence with cardiac-triggered segmented acquisition (fastcard) was compared with a standard T1-weighted spin-echo sequence with cardiac gating and respiratory compensation in the evaluation of pediatric patients with thoracic cardiovascular anomalies. Twenty patients aged 1 week to 24 years (median age, 9 months) with various abnormalities underwent magnetic resonance (MR) imaging. In 18 patients, MR imaging was performed with both gated spin-echo and fastcard. Two observers rated the clinical utility of each sequence. Fastcard images were superior to spin-echo images in 10 patients, equivalent in seven, and inferior in one. Two additional patients with suspected pulmonary vascular lesions were accurately evaluated with the fastcard technique. The fastcard technique provides superior demonstration of thoracic cardiovascular structures and turbulent flow and enables imaging in multiple phases of the cardiac cycle. PMID- 8351347 TI - Testicular torsion in infants and children: diagnosis with Doppler sonography. AB - The accuracy of Doppler sonography in the evaluation of testicular torsion was tested in 65 boys (aged 0-18 years) with acute scrotal pain or swelling. All patients underwent pulsed Doppler sonography of both testes, followed by scintigraphy (n = 16) and/or surgery (n = 34) and a close clinical follow-up for 4-8 months (n = 31). Color Doppler sonography was performed in 29 patients. The testicular artery was deemed patent if Doppler shifts from branches within the parenchyma could be found. Surgery revealed 19 cases of testicular torsion, 17 of which were diagnosed with Doppler sonography. There were six technical failures, in which no signals could be found on either side. In four boys, no color signals were obtained in either testis but subsequent examination with a mechanical sector scanner and pulsed Doppler sonography yielded arterial signals. Doppler sonography was successful in 59 of 65 boys (91%) and yielded a sensitivity of 89% and specificity of 100%. Pulsed Doppler sonography with mechanical sector scanners was more sensitive than color Doppler sonography. Intermittent torsion was missed both with Doppler sonography and scintigraphy. PMID- 8351349 TI - Proton MR and human cervical neoplasia: ex vivo spectroscopy allows distinction of invasive carcinoma of the cervix from carcinoma in situ and other preinvasive lesions. AB - The concept that high-resolution (8.5-T) hydrogen-1 magnetic resonance (MR) spectroscopy can be used as an adjunct to conventional histologic diagnosis of cervical neoplasia was investigated. Cervical biopsy specimens (n = 159) were examined with H-1 MR spectroscopy and the results compared with results of histopathologic analysis. A high-resolution lipid MR spectrum was observed in 39 of 40 invasive carcinomas, whereas the 119 preinvasive samples showed little or no lipid spectrum but were characterized by a strong unresolved resonance between 3.8 and 4.2 ppm. Peak ratios of the methylene/methyl and the unresolved/methylene resonances allowed accurate distinction between invasive and preinvasive epithelial malignancy (P < .0001). Since MR spectroscopic examination does not destroy the specimen, the specimens remained intact for further testing and histopathologic analysis. The authors conclude that H-1 MR spectroscopy can independently allow distinction between invasive and preinvasive lesions of the cervix and has the potential to assist in clinical management of cervical cancer. PMID- 8351348 TI - Fluoroscopically guided percutaneous suprapubic cystostomy for long-term bladder drainage: an alternative to surgical cystostomy. AB - Percutaneous large-bore suprapubic cystostomy catheters were placed under fluoroscopic guidance in 60 patients as an alternative to surgical cystostomy. Foley catheters (16-20 F) were placed in 57 of the patients in a one-stage procedure. Ten-French catheters were initially placed in three patients because of difficulty in dilating percutaneous tracks because of obesity (one patient) or dense scar tissue (two patients). Three weeks later, 18-F Foley catheters were placed in these three patients when mature tracks had developed, making dilation easier. Minor complications occurred in three patients, including superficial track bleeding in two and urosepsis in one. Fifteen patients were lost to follow up. Suprapubic catheters provided excellent long-term drainage (range, 0.5-36 months; mean, 16 months; median, 18 months) in the remaining 45 patients. The authors conclude that percutaneous suprapubic catheter placement is a safe and effective procedure that provides excellent long-term bladder drainage. PMID- 8351350 TI - Carcinoma of the cervix: value of plain and gadolinium-enhanced MR imaging in assessing degree of invasiveness. AB - The accuracy of nonenhanced spin-echo (SE) T2-weighted and contrast material enhanced SE T1-weighted magnetic resonance (MR) imaging in assessing the degree of local tumor invasion was determined prospectively in 53 consecutive patients with clinically established early-stage carcinoma of the cervix. With a 0.5-T superconducting unit, pulse sequences of 2,000/90 (repetition time msec/echo time msec) for T2-weighted images and 500/20 for T1-weighted images were used. In all cases, findings of the two MR imaging techniques were compared with results of histologic examination of surgical specimens. Tumor infiltration into the surrounding structures was classified as partial stromal, complete stromal, or parametrial. Tumor-cervical stroma and tumor-parametrium contrast-to-noise ratios (C/Ns) were higher (P < .05) at nonenhanced T2-weighted than at enhanced T1 weighted than at enhanced T1-weighted imaging. In determining the depth of invasion, the overall accuracy was 85% for nonenhanced T2-weighted and 57% (P < .05) for enhanced T1-weighted imaging. With conventional SE sequences, nonenhanced T2-weighted MR imaging is superior to contrast-enhanced T1-weighted MR imaging in determining the degree of invasiveness in clinical early-stage cervical tumors. PMID- 8351351 TI - Mammographic positioning: evaluation from the view box. AB - To evaluate the quality of breast positioning for mediolateral oblique (MLO) and craniocaudal (CC) views, a prospective study of 1,000 consecutive bilateral screening mammographic examinations was performed. Six criteria were tested, including depth of tissue seen, inferior extent of the pectoral muscle relative to the posterior nipple line, presence of fibroglandular tissue at the posterior edge of the film, and whether the nipple was in profile. Pectoral muscle was depicted to within 1 cm of the nipple line or below it on 1,612 of the 2,000 MLO mammograms (81%); all fibroglandular tissue was depicted on 1,532 MLO mammograms (77%). The depth of tissue depicted on the CC mammogram was within 1 cm greater or less than the depth on the MLO mammogram on 1,586 CC mammograms (79%); the pectoral muscle was seen on 646 CC mammograms (32%). The nipple was in profile in 1,769 MLO mammograms (88%) and 1,783 CC mammograms (89%) but not in profile in either view in 83 cases (4%). Overall improvement was seen in 400 of 587 examinations (68%) when new mammograms were compared with previous mammograms. These criteria can be used to evaluate positioning performance and for quality control. PMID- 8351352 TI - Acute puerperal breast abscesses: US-guided drainage. AB - Breast abscesses typically develop in lactating women. The recommended treatment is surgical incision and drainage with the patient under general anesthesia. Ultrasonically guided percutaneous drainage with local anesthesia was performed in 19 consecutive patients referred for treatment because of clinical signs of acute puerperal breast abscess. Eighteen of the 19 patients (95%) were successfully treated. Long-term follow-up (median, 12 months) did not show any recurrences, and the cosmetic results were excellent. Eight of the 19 patients (42%) continued nursing during and after treatment. Ten of the 19 (53%) were treated on an outpatient basis. On the basis of these results, the authors recommend ultrasonically guided percutaneous treatment for use in patients with acute puerperal breast abscesses. PMID- 8351353 TI - Quality assurance and cancer detection rates in a provincial screening mammography program. Work in progress. AB - In 1990, a provincial screening program was inaugurated in Alberta, a Canadian province of 2.4 million people. The goal of the program is to decrease the number of deaths from breast cancer by 30% in women aged 50-69 years. In the first 18 months of program operations, efforts were concentrated on high levels of quality assurance in all areas of program activities. In particular, the abnormality referral rates, cancer detection rates, and size and stage of mammographically detected cancers were evaluated. Of the 9,553 women seen, 8,524 were between the ages of 50 and 69 years. Reported abnormality rates were initially more than 16%, but were brought down steadily to less than 5%. Cancer detection rates increased with age, ranging from 1.9 cancers detected per 1,000 women aged 40-49 years to 14.1 cancers per 1,000 women aged 70 years and older. Forty-one of the 61 cancers detected (67%) were less than 1.5 cm in diameter. Forty-three of the 52 cancers (83%) in which the nodal status was known were node negative. At the conclusion of the first 18 months of operation, interpretation parameters were within the target zones expected for a population-based screening program. PMID- 8351354 TI - Acute interstitial pneumonia: radiographic and CT findings in nine patients. AB - The radiologic findings were reviewed in nine patients with biopsy- or autopsy proved acute interstitial pneumonia (AIP). All patients had bilateral air-space opacification on radiographs and bilateral, symmetric areas of ground-glass attenuation on computed tomographic (CT) scans. The areas of ground-glass attenuation had a patchy distribution in six patients (67%) and were diffuse in three patients. Air-space consolidation was seen at CT in six patients (67%) and involved mainly the lower lung zones in three patients and upper lung zones in one patient and was diffuse in two patients. A predominantly subpleural distribution of the consolidation was present in two patients. Eight of the nine patients died within 3 months of presentation. The authors conclude that the radiographic and CT features of AIP are similar to those of adult respiratory distress syndrome and represent acute alveolar damage. AIP differs from the more chronic forms of interstitial pneumonia in clinical presentation and in pathologic and radiologic findings. PMID- 8351355 TI - Intracavitary aspergilloma: transthoracic percutaneous injection of amphotericin gelatin solution. AB - For aspergillomas in patients with fibrocavitary lung disease, surgery is often not recommended. Injection or lavage of the cavities with solutions of potassium iodide or antifungal agents has had varying success and requires repeated sessions because of nonretention of the therapeutic agent within the cavity. In three patients with four aspergillomas, the authors used fluoroscopic or computed tomographic (CT) guidance to inject amphotericin in gelatin as a liquid that solidifies within the cavity at body temperature. The patients were followed up with serial chest radiography or CT. The mixture was successfully instilled in every case. Three of the four aspergillomas completely resolved within 3 months or less, with no evidence of recurrence at follow-up of 6-18 months. The remaining aspergilloma decreased in size, but the patient needed pneumonectomy because of recurrent hemoptysis within 6 months of amphotericin injection. Transthoracic instillation of a liquid mixture of amphotericin and gelatin that solidifies rapidly at body temperature may be useful as a one-step treatment for aspergillomas. PMID- 8351356 TI - Inoperable pulmonary aspergilloma: percutaneous CT-guided injection with glycerin and amphotericin B paste in 15 cases. AB - Fifteen patients with active inoperable pulmonary aspergilloma underwent percutaneous injection of a special therapeutic paste of glycerin and amphotericin B. This paste was warmed just prior to injection, and filling of the lesional cavity was achieved in one session if it was possible to obtain anaerobic conditions for destruction of the aspergilloma. Injection was performed with computed tomographic guidance with use of an 18-gauge flexible needle and with administration of anti-coughing analgesia. Follow-up was continued for 7 months on average. Filling of the lesion cavities required three sessions on average because of cough or bronchospasm. In 12 cases the aspergilloma regressed within 3 months and results at serology became negative. In three cases, there was no change in the cavity, but hemoptysis did not recur. Results in this series confirm the feasibility and efficacy of this palliative treatment. PMID- 8351357 TI - Uncomplicated asthma in adults: comparison of CT appearance of the lungs in asthmatic and healthy subjects. AB - A study was undertaken to define the computed tomographic (CT) appearance of the lungs in subjects with uncomplicated asthma and to compare the prevalence of bronchial dilatation at CT in asthmatic and healthy subjects. Clinical features, pulmonary physiologic findings, chest radiographs, and high-resolution CT scans of 48 asthmatic subjects were reviewed. Forty-one (85%) of the 48 asthmatic subjects were undergoing bronchodilator therapy, 28 (58%) were undergoing steroid therapy, and 21 (44%) were cigarette smokers. Twenty-seven healthy control subjects underwent limited high-resolution CT. At selected CT levels, any bronchus with an internal diameter greater than that of the accompanying pulmonary artery was considered dilated. In the asthmatic subjects, 153 (36%) of 429 bronchi evaluated met criteria for bronchial dilatation compared with 37 (26%) of 142 bronchi in the control group (P < .05). Because bronchial dilatation demonstrated at CT did not correlate with clinical data, the authors conclude a bronchus larger in diameter than the adjacent vessel is not sufficient evidence to diagnose cylindric bronchiectasis. PMID- 8351358 TI - Automated in vivo quantification of emphysema. AB - A computer program to automatically determine lung volume and percentage of emphysema from computed tomographic (CT) chest sections was developed. To test it, the authors reviewed scans obtained in 89 patients. Any computer errors in identification of normal or emphysematous lungs were corrected manually by tracing the boundaries of the lungs or eliminating areas of nonemphysematous lung with a roller ball. The corrected values were compared with the uncorrected values. In 33 patients from the study group, lung volumes and the percentage of emphysema were calculated by using a currently available "voxel highlighting" program. Successful computerized analysis of entire lungs was performed in 1 minute, compared to more than 1 hour for manual analysis. Correlation was high (r = .99) between results obtained manually and those obtained with the computer. Although the difference between uncorrected and corrected values of the percentage of emphysema was statistically significant, this converted to a correction of only 0.1%. The computer program allowed quick, accurate, and reproducible quantification of emphysema. PMID- 8351359 TI - Pulmonary embolism: diagnosis with electron-beam CT. AB - Contrast material-enhanced electron-beam computed tomography (CT) (100-msec scan time) was performed to image the pulmonary vasculature in 86 patients, each suspected of having a pulmonary embolism (PE). Thromboembolic material was demonstrated in 39 patients; no emboli were demonstrated in 47. In 25 patients, angiographic or pathologic proof was available. There were 19 proved positive CT scans, four proved negative scans, one false-negative scan, and one false positive scan. In the 21 patients with CT and angiographic correlation, evidence of thromboembolic disease was seen in 88 vascular zones. Fifty-three zones were positive for PE at both CT and angiography. Eighteen zones were positive for PE at angiography alone, and 17 zones were positive at CT alone. Electron-beam CT is a potentially effective noninvasive means of diagnosing PE. PMID- 8351360 TI - Detection of unsuspected central pulmonary embolism with conventional contrast enhanced CT. AB - When fast, nondynamic scanning techniques are used in combination with adequate intravenous injection of contrast material, good-quality images of the pulmonary artery (PA) can be obtained with routine computed tomography (CT). The purpose of this study was to evaluate PA filling defects detected on these CT scans. Twenty two CT scans from 22 patients with PA filling defects were reviewed. A routine scanning technique was used. Thrombus was unilateral in 12 cases and bilateral in 10. All patients but one had a predisposition for pulmonary embolism (PE). However, only five patients underwent CT because there was a strong suspicion for PE. In 17 cases, PE was not the first choice of clinical diagnosis; in 13 cases, thrombus of the PA was not even considered. Diagnosis was confirmed in 11 patients with ventilation-perfusion scanning (n = 7), angiography (n = 3), and surgery (n = 1). In 11 patients, anticoagulation therapy was started without further diagnostic procedures. Diagnosis of thrombus of the PA is possible with routine nondynamic, contrast material-enhanced CT. Because PE is often unsuspected at clinical examination, every contrast-enhanced CT scan of the chest should be evaluated for the presence of filling defects in the PA. PMID- 8351361 TI - Percutaneous inferior vena caval filters: follow-up of seven designs in 320 patients. AB - Three hundred twenty-four percutaneous inferior vena caval (IVC) filters of different designs were placed in 320 patients from April 1985 through June 1992. No acute mortality or substantial morbidity was attributed to filter placement. Radiologic or pathologic follow-up data were obtained in 227 (71%) patients (230 filters); clinical follow-up data only were obtained in 50 (16%) patients (50 filters). One hundred twenty (43%) patients died; post-filter-placement pulmonary emboli (PE) were related to the cause of death in eight. At IVC filter imaging studies, 26 of 137 (19%) filters demonstrated caval thrombus; 12 of 132 (9%) filters had delayed penetration through the IVC wall of greater than 3 mm; 13 of 230 (6%) filters migrated more than 1 cm; and five of 230 (2%) filters had fracture of a strut or leg. Deep venous thrombosis (DVT) at the insertion puncture site or in the lower extremity was noted in 26 of 117 (22%) cases of filter placement. Among patients without imaging studies, clinical suspicion of complications included PE in four patients, IVC thrombus in 14 patients, and lower-extremity DVT in 10 patients. Long-term clinical and radiologic follow-up of all IVC filters is indicated due to the relatively high prevalence of some complications. PMID- 8351362 TI - Vena Tech-LGM filter: long-term results of a prospective study. AB - Efficiency and tolerance of the Vena Tech-LGM filter were assessed in 142 patients prospectively studied during a 2-6-year follow-up period. No patients were lost to follow-up, and 137 (91.3%) scheduled control examinations were performed. Fifty-three patients died of causes unrelated to thromboembolic disease. Pulmonary embolism was suspected in five surviving patients (3.5%). Sixteen retractions (18.4%), 16 intracaval migrations (18.4%), and one tilt were observed. Filter patency studied at Doppler ultrasonography, with or without phlebocavography, gave the following results according to the Kaplan-Meier actuarial method: 92% patency after 2 years of follow-up, 80% after 4 years, and 70% after 6 years. Vena Tech-LGM filter obstruction was related to retraction (P < 10(-6)) or distal migration (P < .004). Occurrence of trophic disease in the lower limbs during the follow-up period was related to the initial level of deep venous thrombosis (P = .03) and had no relation to the patency of the filter. The filter was effective in preventing pulmonary embolism, with 70% demonstrating long-term patency, and no deleterious effects were imputed to obstructions observed during follow-up. PMID- 8351363 TI - Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion. AB - A prospective randomized controlled trial compared forced infusion (FI) of urokinase (UK) with conventional slow continuous infusion (CI) in 25 patients with 25 acutely ischemic lower limbs. Demographics, ischemia categories, and infusion rates and doses were similar for both groups. A preliminary single-pass bolus of UK was injected into the thrombus in all patients with a pulsed-spray technique, and heparin was administered. UK was then infused with a CI pump (n = 13) or a prototype pulsed-spray pump (n = 12). The primary end point was patency, defined as at least 95% thrombolysis by volume, with brisk antegrade flow occurring within 4 hours. Eleven of the 12 patients (92%) who underwent FI and nine of the 13 (70%) who underwent CI had patency within 4 hours. However, 10 patients who underwent FI and nine who underwent CI had residual thrombi prolonging infusion. No significant differences between the two groups were apparent in speed of lysis, initial success rates, complication rates, or 30-day clinical outcome. Lytic therapy, however, was completed within 24 hours in 18 of 23 (78%) successfully treated patients (P = .01). PMID- 8351364 TI - Improved mammography with a reduced radiation dose. AB - A 2-cm-high focused air-interspaced grid with a 7:1 ratio and eight lamellae per inch was devised. The grid is arc-shaped and pivots on its focal point, the anode cathode axis. Milliamperage was 35% less for breast phantom radiographs obtained with the new grid versus those obtained with a conventional 5:1 mammographic grid. In a comparison study of five mammograms, each evaluated for five parameters, the images obtained with the new grid were judged to be of equal or better quality than those obtained with a conventional grid in 17 of 20 comparisons. PMID- 8351365 TI - Catheter for percutaneous thrombectomy: first clinical experience. AB - The authors evaluated a double-lumen thrombectomy catheter that functions by way of the Venturi effect in seven consecutive patients with thrombus in the superficial femoral artery. The estimated age of the thrombotic material was between 3 days and 9 weeks. Thrombectomy was successful in all patients, and mean time required was less than 20 minutes. In five patients, diagnosis, thrombectomy, and therapeutic intervention were successfully performed in one session. PMID- 8351366 TI - Film density calibration for computed radiography systems: is the standard three point procedure accurate? AB - With computed radiography (CR) systems, laser printer-film processor combinations are normally checked daily by using test film three-point density measurements. In this study, the authors show that the recommended three-point quality assurance procedure can show satisfactory results even though the CR film output behaves in an anomalous manner. This problem can be corrected by using a 16-point calibration procedure. Regular 16-point calibrations should be performed to ensure satisfactory CR system performance. PMID- 8351367 TI - Intraorbital wood foreign bodies. PMID- 8351368 TI - Contrast and signal-to-noise ratio in radiographic images. PMID- 8351369 TI - A step forward in the characterization of adrenal cortical lesions? PMID- 8351370 TI - Fluid-fluid level in bronchogenic cysts. PMID- 8351371 TI - [Bacterial dysentery in 1991]. PMID- 8351372 TI - [Distribution of antibodies against Encephalitis ixodica viruses among north-east healthy populations of Poland]. AB - We have undertaken the investigations for the detection of the presence of antibodies against Encephalitis ixodica viruses among North-East population of Poland. We have found these antibodies in 6.5% among 676 of tested healthy persons. The highest % of detected antibodies were noted in forest rangers and in physicians acting as hunters. Our data seems to indicate that Encephalitis ixodica is still actual disease in this region. Therefore one can suggest the necessity vaccination against Encephalitis ixodica. PMID- 8351373 TI - [Food poisonings and infections in 1991]. PMID- 8351374 TI - [Poisoning from chemicals used for plant protection in 1991]. PMID- 8351375 TI - [Viral hepatitis B in 1991]. PMID- 8351376 TI - [Non-b viral hepatitis in 1991]. PMID- 8351377 TI - [Tetanus in 1991]. PMID- 8351379 TI - [Brucellosis in 1991]. PMID- 8351378 TI - [Rabies in 1991]. PMID- 8351380 TI - [Trichinosis in 1991]. PMID- 8351381 TI - [Aids and HIV infections in 1991]. PMID- 8351382 TI - [Kazimierz Albin Lachowicz. Doctor of microbiology 1909-1992]. PMID- 8351383 TI - [Etiologic profile of viral respiratory infections in small children during epidemic periods 1990-91 and 1991-92]. AB - In periods from October 1990 to June 1991 and from September 1991 to June 1992, 551 hospitalized infants and small children were examined by immunofluorescence method for respiratory viruses. In 264 (47.9%) cases viral etiology was established. Like in previous seasons the infections of RS and parainfluenza type 3 viruses dominated. Infections of RS virus were not frequent, and of parainfluenza type 3 virus less than in previous seasons. The increase of percent of infections due to parainfluenza type 2 and 4 viruses were observed. PMID- 8351384 TI - [Neurotropic properties of Listeria monocytogenes and Mycobacterium leprae in natural and experimental infections]. PMID- 8351385 TI - [Infant mortality and perinatal mortality in Poland in the eighties. II. Deaths by birthweight]. AB - The dynamics of the changes in the level of the birthweight-specific infant mortality and perinatal mortality rates by age and cause during the eighties is presented. The strongest decline in the birthweight-specific infant and perinatal mortality rates is observed among the newborns weighing less than 2500 g. The level of the low birth weight (7.9% in 1989) and despite the decrease--the infant and perinatal mortality rates among the newborns weighing 1001-2500 g (100.5 and 109.4 respectively in 1989) and among the newborns weighing 601-1000 g (865.3 and 851.1 respectively in 1989) are high comparing to the developed countries. PMID- 8351386 TI - [Actual state of medical supply sterilization in Poland]. AB - The analysis of condition of sterilization of medical supplies in Poland was done. It consider the problem of preparation of medical supplies to sterilization, methods of sterilization and control monitoring system in this matter. The results of this analysis suggest proposition for improving of activities in this field. PMID- 8351387 TI - [Certain problems with limits of immunity against measles, mumps and rubella]. AB - Strategic goals and schemes of immunization against measles, mumps and rubella in European countries with special attention for positive and negative sides of immunization against rubella and control of congenital rubella were described. Vaccines against mumps with strain Urabe AM9 were withdrawn in September 1992 in Great Britain. Decision was caused by increasing of complications after vaccination to 1 for 4000 doses of vaccine. (Former 1:4,000,000). Only mumps vaccine with strain Jeryl Lynn is there accepted. Including of vaccination against mumps to the calendar of vaccination in Poland was advised, when vaccine MMR with Jeryl Lynn mumps vaccine strain would be available. Monitoring of immunization of women against rubella would be necessary after above mentioned change in calendar of vaccinations. PMID- 8351388 TI - [Infectious diseases in Poland in 1991]. PMID- 8351389 TI - [Measles in 1991]. PMID- 8351390 TI - [Whooping cough in 1991]. PMID- 8351391 TI - [Scarlet fever in 1991]. PMID- 8351392 TI - [Epidemic parotitis in 1991]. PMID- 8351393 TI - [Influenza in 1991]. PMID- 8351394 TI - [Rubella in 1991]. PMID- 8351396 TI - [Salmonellosis in 1991]. PMID- 8351395 TI - [Cerebrospinal meningitis and encephalitis in 1991]. PMID- 8351397 TI - [Psychoanalytic theories of gender identity]. PMID- 8351398 TI - [Female genital anxieties and conflicts and typical coping mechanisms]. PMID- 8351399 TI - [Neutrality, bisexuality and androgyny of the psychoanalyst]. AB - Proceeding from the fact that Western thought is based on Greek philosophy, the author pinpoints a feature specific to psychoanalysis. Unlike other sciences, which are grounded in the central (and latently homosexual) relation of rhetoric and dialogue between teacher and pupil, psychoanalytic dialogue centers around a heterosexual (male/female) relationship. Prototypic for this is the confrontation of the psychoanalyst with the "complex burden of female love". The fascination of philosophy lies in similarity, that of psychoanalysis in difference. The gender question, and more specifically the sex of the analyst, has been given little attention in connection with the transference/countertransference paradigm. With a discussion of the concepts of neutrality (Freud), bisexuality (Freud, Jung) and with reference to literary sources on androgyny (V. Woolf, Balzac, Le Guin) Molfino undertakes the attempt to take the gender discussion in psychoanalytic theory and practice a stage further. PMID- 8351400 TI - [A lady vanishes: Sophie Freud and Beyond the Pleasure principle]. PMID- 8351401 TI - Cosecretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets following stimulation or inhibition of beta-cell function. AB - The aim of this work was to simultaneously study the secretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets in vitro. For examination of stimulated beta-cells, nutrient secretagogues (16.7 mM glucose, 10 mM leucine + 2 mM glutamine), phosphodiesterase inhibition (5 mM theophylline), a sulphonylurea (0.5 microgram/ml glipizide), a non-nutrient amino acid (10 mM arginine), cholinergic stimulation (0.1 mM carbamylcholine) and insulinotropic peptides (0.1 microM vasoactive intestinal polypeptide and 0.1 microM glucagon), were used. For beta-cell suppression glucose phosphorylation inhibition (10 mM mannoheptulose), depletion of extracellular calcium, activation of the ATP regulated K(+)-channel (0.5 mM diazoxide), adrenoreceptor stimulation (3 microM adrenaline), paracrine modulation (0.1 microM somatostatin), short-term treatment with a selective beta-cytotoxin (1.1 and 2.2 mM streptozotocin) and long-term treatment with a cytokine (25 U/ml interleukin-1 beta), were studied. The compounds with known effects on insulin secretion exerted their expected actions and this was paralleled by similar relative changes, with a possible exception for glucagon, in the IAPP secretion. The ratio of IAPP/insulin released did not change significantly under any of the tested experimental conditions, except for a slight increase following carbamylcholine stimulation. On a molar basis approx. 1% of IAPP was released when compared with insulin. These results are consistent with the hypothesis that the regulation of IAPP secretion from beta-cells of isolated rat pancreatic islets is essentially regulated by the same mechanisms as insulin secretion. PMID- 8351402 TI - The effects of intravenous cholecystokinin, secretin and pentagastrin on electromyographic activity of the rumen in sheep. AB - Several gastroenteropancreatic (GEP) peptides have been reported to alter ruminal motility. In the present study, we tested the effects of three of these peptides on ruminal myoelectrical activity in the sheep. We measured the effect of 10 min IV infusions of pentagastrin, secretin, and cholecystokinin, either alone or in combination, on the spike frequency of the rumen in conscious sheep. IV administration of 780 pmol/kg pentagastrin significantly decreased spike frequency within 10 min with a return towards control levels over the subsequent 30 min. Secretin decreased ruminal spike activity at doses of 120 and 180 pmol/kg. Finally, 13, 26 and 35 pmol/kg IV cholecystokinin all resulted in significant decreases of spike frequency, with virtual elimination of spiking activity at the highest dose. Administration of the lowest dose of secretin, or the single dose of pentagastrin, with the lowest dose of CCK resulted in a potentiation of their inhibitory effects. We conclude that one mechanism underlying the altered motility induced by these GEP peptides is a decrease of spike frequency which may contribute to overall contractile activity. PMID- 8351403 TI - Primary structure of neuropeptide Y from brains of the American alligator (Alligator mississippiensis). AB - The purification of NPY from brains of the American alligator (Alligator mississippiensis) was achieved using reverse-phase high performance liquid chromatography (HPLC). The amino acid sequence was determined using automated Edman degradation as Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu- Asp-Ala-Pro-Ala-Glu Asp-Met-Ala-Arg-Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile- Asn-Leu - Ile-Thr-Arg-Gln Arg-Tyr. Alligator NPY is the first non-mammalian vertebrate to have 100% sequence identity to human NPY. The conservation of alligator NPY suggests that serine in position 7 of chicken NPY evolved after the birds and reptiles diverged from a common Archosaurian ancestor. Furthermore, the sequence identity between alligator and human NPY suggests this sequence is the same as the ancestral amniote NPY. PMID- 8351404 TI - Neuropeptide Y and neuropeptide Y 3-36: isolation from human pancreatic endocrine tumours. AB - Using an antiserum raised to the C-terminal region of neuropeptide Y (NPY) which does not cross-react with pancreatic polypeptide (PP), immunoreactivity has been detected in two different endocrine tumours of the human pancreas in concentrations permitting isolation and structural analysis. In a clinically typical gastrinoma, resected from the head of pancreas, the concentration of NPY immunoreactivity was 3.4 nmol/g. Reverse phase HPLC analysis of extracts of this tumour resolved a single immunoreactive peptide coeluting with synthetic human NPY. The molecular mass of the isolated peptide, determined by mass spectroscopy, was 4270 Da, which was in close agreement with that derived from the deduced primary structure of human tumour NPY (4271.7 Da), obtained by gas-phase sequencing. A somatostatinoma, resected from the region of the ampulla of Vater, contained 3.8 nmol/g of NPY immunoreactivity and isolation of this immunoreactive peptide followed by structural analyses, indicated a molecular structure consistent with NPY 3-36. These data suggest that NPY immunoreactivity detected in human pancreatic endocrine tumours is molecularly heterogenous, a finding which may be of relevance in the symptomatology of such tumours as attenuation of the N-terminus of this peptide generates receptor selectivity. PMID- 8351405 TI - Differences between perinatal angiotensin binding in the brains of SHR and WKY rats. AB - A growing body of evidence suggests that angiotensin may have a functional role in growth and development, in addition to its classical role in the maintenance of body water homeostasis. Components of the renin-angiotensin system have been identified in the rat fetus. Because of the association between the renin angiotensin system and hypertension, we quantified angiotensin receptor binding sites in the brains of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats during perinatal development. Using in vitro receptor autoradiography we identified specific 125I-Sar1,Ile8 AII binding in several areas of the brains of perinatal rats of both strains and observed significant differences in the concentration of binding sites, at different ages in several brain nuclei. With the knowledge that components of the renin-angiotensin system appear early in development and are known to have an association with cellular growth, it is possible that an irregularity in this system occurring during neurogenesis could contribute to developmental abnormalities, as well as subsequent hypertension. PMID- 8351408 TI - [French Society of Pneumology. List of members (1993)]. PMID- 8351406 TI - Enteroendocrine peptides in a canine model of orthotopic jejunoileal autotransplantation. AB - The enteroendocrine cells of the small bowel provide a rich source of regulatory peptides involved in the modulation of gastrointestinal function. Recent work from our laboratory showed that in situ neural isolation (autotransplantation) of the jejunoileum produced marked changes in tissue expression of several neuropeptides. In the present study, we examined the influence of extrinsic innervation on the tissue expression of endocrine peptides localized to various regions of the gastrointestinal tract. Concentrations of immunoreactive gastric inhibitory polypeptide (GIP), neurotensin (NT) and peptide tyrosine tyrosine (PYY) in fasting plasma and regional tissue biopsies were determined before and at varying time points (2, 6, 12 weeks) after a model of canine orthotopic jejunoileal autotransplantation. GIP was not altered in plasma or tissue at any time point. Plasma concentrations of NT and PYY increased after autotransplantation. Following a decrease in tissue concentrations two weeks after autotransplantation, NT increased progressively from 2 to 6 to 12 weeks, reaching a maximal increase of 895% over baseline in proximal ileum. Tissue concentrations of PYY followed much the same pattern as NT, but these trends never achieved statistical significance. Chromatographic characterization of tissue biopsy extracts revealed molecular heterogeneity of NT-like immunoreactivity, while GIP and PYY immunoreactivity coeluted as single species with authentic standards. Taken together with our earlier observations, it appears that disruption of extrinsic and intrinsic neural continuity to the jejunoileum (autotransplantation) does not affect gut endocrine peptides such as GIP and PYY to the same extent as enteric neuropeptides. NT has been localized to neural as well as endocrine cells and is involved in the temporal adaptive response to autotransplantation. PMID- 8351407 TI - Helospectin/helodermin-like peptides in guinea pig lung: distribution and dilatory effects. AB - The lower airways of guinea pigs were analysed for helospectin and helodermin using immunocytochemistry. A moderate supply of helospectin/helodermin-like immunoreactive nerve fibers and few nerve fibers displaying helodermin immunoreactivity was seen in the smooth muscle, around seromucous glands and small blood vessels in the trachea and around bronchi and pulmonary blood vessels. Helospectin I-, helospectin II- and helodermin-induced suppression of smooth muscle responses were analysed using isolated circular segments of trachea and pulmonary arteries of guinea pigs. In both airways and arteries the peptides caused a concentration-dependent relaxation of precontracted segments. The maximal relaxant activity observed was more pronounced in the airways than in the arteries. The effects of the helospectins and helodermin were compared to those of vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), pituitary adenylate cyclase activating peptide (PACAP) and acetylcholine (ACh). All peptides, with the exception of PACAP, caused a total or nearly total relaxation of the precontracted tracheal segments. In the trachea PACAP was significantly more potent than the other five peptides whereas only small potency differences were seen in the pulmonary artery. The relaxant responses to helospectin I, helospectin II and helodermin in the trachea and the intrapulmonary arteries were unaffected by pretreatment with atropine, prazosin, yohimbine, propranolol, mepyramine and cimetidine. Conceivably, nerve fibers containing helospectin and helodermin may play a role in the regulation of airway resistance and in the regulation of local pulmonary blood flow. PMID- 8351410 TI - Insulin like effects of lithium and vanadate on the altered antioxidant status of diabetic rats. AB - Lithium is widely used for treatment of behavioral disorders and has been shown to possess insulin-mimetic properties. The present study examines the in vivo effects of lithium alone, as well as in combination with vanadate (a potent insulin-mimetic agent), on the altered antioxidant status in the liver and kidney of diabetic rats. The elevated blood glucose levels in diabetic rats were about 50% restored by oral administration of lithium (0.3 mg/ml) and were completely normalized following vanadate addition (0.05 mg/ml) to lithium. Lithium therapy effectively normalized the decreased activities of catalase (CAT) and glutathione peroxidase (GSH-PX) but could not restore the lowered superoxide dismutase (SOD) in the liver of diabetic rats; while in kidney, the treatment proved to be ineffective. Inclusion of vanadate produced synergistic effect and caused partial restoration of the altered CAT, GSH-PX and CuZn-SOD levels in diabetic kidney and the depressed SOD activity in diabetic liver. These results suggest that lithium therapy may prove effective in improving the impaired antioxidant status during diabetes and vanadate supplementation at a low dose potentiates the effectiveness of lithium action. PMID- 8351409 TI - Pathways of formation of 2-, 3- and 4-bromophenol from bromobenzene. Proposed mechanism for C-S lyase reactions of cysteine conjugates. AB - Bromobenzene is metabolized by the rat and guinea pig to 2-, 3- and 4 bromophenol. 3-Bromophenol is formed through the sulfur-series pathway to phenols. This route involves the enterohepatic circulation; the key intermediate is the S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine derived from the 4-S glutathione conjugate of the 3,4-oxide. A sulfonium ion C-S lyase reaction is proposed in order to account for the pyridoxal phosphate-dependent cleavage/aromatization step, and a C-S beta-lyase reaction sequence is also proposed for the formation of bromodihydrobenzene thiolols. This route of phenol formation may prove to be a general one for aromatic hydrocarbons and closely related compounds that show arene oxide conjugation with glutathione. 2 Bromophenol is formed predominately by spontaneous isomerization of the 2,3 oxide. 4-Bromophenol is formed by the sulfur-series route from the S-(2-hydroxy-5 bromocyclohexa-3,5-dienyl)-L-cysteine. Additional in vivo routes to 3- and 4 bromophenol involve dehydration/aromatization of the 3,4-dihydro-3,4-diol, possibly by way of conjugates; these routes have transient ketonic intermediates. The pathways from bromobenzene to phenols and to sulfur-containing metabolites derived from premercapturic acids show species and dosage variation. PMID- 8351411 TI - beta-Casomorphin-immunoreactivity in the brain stem of the human infant. AB - Using a peptide extraction procedure, reversed phase high performance liquid chromatography, and a radioimmunoassay that utilized an antibody raised specifically against human beta-casomorphin-8 (BC8), BC-immunoreactivity (BCIR) was detected in rostrocaudally increasing levels in nineteen microscopically distinct and functionally relevant areas of mesencephalon, pons cerebri, and medulla oblongata of eight infants. On the basis of the methodology used, it can be concluded, that the BCIR present in their brain stem was due to BC8 and/or to some of its congeners. Data in the literature together with those of this study indicate that beta-casomorphins could be transported by specific mechanisms from the blood into the brain stem and that they could play a role in the central regulation of various physiological phenomena. PMID- 8351412 TI - Immediate decline in DNA synthesis in neonatal rat lung caused by exposure to 100% oxygen. AB - Oxygen therapy in preterm infants is associated with bronchopulmonary dysplasia, but the relative importance of oxygen toxicity as compared to adverse effects of intubation and mechanical ventilation, remains uncertain. In freely-breathing neonatal rats, exposure to 100% oxygen for as little as 2 hr produced a significant reduction in lung DNA synthesis, evaluated by [3H]thymidine incorporation, without a concomitant effect on [3H]leucine incorporation into protein. These results indicate that hyperoxia has a selective deleterious effect on mitosis in developing lung. PMID- 8351413 TI - Nature of heme metabolizing enzymes in a mutant rat with hyperbilirubinuria. AB - Eisai hyperbilirubinuria rat (EHBR) is a mutant strain which is originated from Sprague Dawley rats. The activities of heme metabolizing enzymes in EHBR were compared with those of Sprague Dawley rats as the control. The activity of delta aminolevulinic acid (delta-ALA) synthetase, the initial and rate-limiting enzyme in heme biosynthesis, was significantly higher in the liver of EHBR. However, no significant difference in the activity of heme oxygenase, the first and rate limiting enzyme in heme degradation, was observed in EHBR as compared to control rats. DDC, a porphyrinogenic agent, caused marked and prolonged increase in the activity of delta-ALA synthetase in EHBR. However, the contents of microsomal total heme and cytochrome P-450 were significantly decreased in EHBR 24 hrs after DDC injection. The activity of heme oxygenase by CdCl2, a inducer of heme oxygenase, was considerably higher in EHBR than in control rats. These results indicate some specific hypersensitivity for heme metabolizing enzymes in EHBR. PMID- 8351414 TI - In vitro cell transformation induced by the pesticide fenarimol. AB - The pesticide fenarimol is capable of transforming BALB/c 3T3 cells in an in vitro model system, and its action resembles a carcinogenic process in vivo. In the absence of metabolic activation, transformed foci are already visible in the standard experimental procedure. The addition of the S9 fraction as an exogenous metabolic system leads to a decrement of cytotoxic effects and the reduction of the transformation rate. The transformed phenotype, however, becomes visible when confluent cells are replated and allowed further cell replication. Transformation effects by fenarimol may be due to both a weak genotoxic activity and/or stronger promoting activity. PMID- 8351415 TI - Accumulation of malondialdehyde in mouse heart following acute dosing with adriamycin is strain specific and unaffected by cardiac catalase status. AB - CDF1 and C57BL/6J male mice were acutely dosed with Adriamycin (ADR), and total cardiac malondialdehyde (MDA) quantitated following isolation by modification of previously developed procedures. Cardiac MDA content in CDF1 mice increased significantly 5 days following ADR dosing as reported by others, but was unchanged in C57BL/6J mice. ADR-induced mortality and a significant loss in cardiac weight 2-3 days after treatment was similar in both strains. Cardiac lipid hydroperoxide (LH) content was also unchanged in C57BL/6J mice dosed acutely with ADR. However, hepatic LH content increased rapidly following treatment with ADR, reaching maximal level 1 day following treatment before returning to below untreated levels 24 hours later. Studies with genetically acatalasemic C57BL/6J mice showed that neither cardiac nor hepatic lipid hydroperoxide content in ADR-dosed animals is affected by tissue catalase levels. These results demonstrate that C57BL/6J mouse heart is refractory to ADR-induced lipid peroxidation (LP) although overall mortality from the drug is unaffected, and do not support the hypothesis that ADR-induced mortality in mice is a consequence of cardiac LP. PMID- 8351416 TI - J5 prevents endotoxin shock in suckling rats. AB - A sublethal dose of endotoxin (lipopolysaccharide: LPS) can induce endotoxin tolerance. It is not well known whether LPS feeding causes endotoxemia and endotoxin tolerance in the newborn. Since Rc mutant Escherichia coli LPS (J5) does not have toxic or lethal effects, J5 is used to induce endotoxin tolerance in this study. This study showed that both an intraperitoneal (ip) injection and feeding of Rc mutant Escherichia coli LPS (J5) induced endotoxin tolerance in suckling rats. PMID- 8351417 TI - Sex-related differences of acetohexamide reductase activities in the liver and kidney of various mammalian species. AB - Sex-related differences of acetohexamide reductase activities in cytosol and microsomes from the liver and kidney of the rat, mouse, guinea pig, hamster and rabbit were examined. Among animal species tested, the rat, guinea pig and rabbit exhibited sex-related differences in the activities. The activities in liver cytosol of the rat and rabbit were higher in the females than in the males, whereas the activity in kidney cytosol of the rabbit was higher in the male than in the female. Furthermore, the activities in liver and kidney microsomes of the rat and that in kidney microsomes of the guinea pig were much higher in the males than in the females. It is interesting to note that significant sex-related differences of acetohexamide reductase activities are found in some animal species other than the rat. PMID- 8351418 TI - Coronary perfusion pressure, end-tidal CO2 and adrenergic agents in haemodynamic stable rats. AB - Coronary perfusion pressure (CPP) determines myocardial perfusion during low flow. CPP correlates with end-tidal CO2 (PetCO2) during cardiac arrest. Recent studies have demonstrated that after adrenaline, increased CPP was associated with decreased PetCO2. Intravenous infusions (4 min, N = 10) or bolus (10 s, N = 6) of methoxamine (60 micrograms/kg), isoproterenol (10 micrograms/kg), adrenaline and noradrenaline (3 micrograms/kg) were compared with saline placebo (0.2 ml/min) during spontaneous circulation in anaesthetized Sprague-Dawley rats. Infusion and bolus of methoxamine, adrenaline and noradrenaline increased CPP between 39 and 46% above baseline. Isoproterenol decreased CPP by 67%. PetCO2 decreased by 27% after bolus and only 10% after infusion of methoxamine but increased after infusion (7%) and bolus (10%) of isoproterenol and after infusion of adrenaline (11%) and noradrenaline (17%). Equipressor bolus of methoxamine, adrenaline and noradrenaline reduced PetCO2 between 10 and 27%. Bolus application induced more alpha-effects and drug infusion more beta-effects in the pulmonary vasculature. Thus, changes in pulmonary vascular resistance and associated increases in dead space were responsible for differences in PetCO2. Alpha-effects increased CPP, decreased P(et)CO2 and conversely, beta-effects decreased CPP but increased PetCO2 indicating caution when P(et)CO2 is used as non-invasive monitor of perfusion, especially after alpha-adrenergic agents. PMID- 8351419 TI - Influence on outcome after cardiac arrest of time elapsed between call for help and start of bystander basic CPR. The Belgian Cerebral Resuscitation Study Group. AB - The exact impact of the 'interval between cardiac arrest (CA) and the start of basic cardiopulmonary resuscitation (CPR) performed by bystanders' on outcome is not fully established. We retrospectively evaluated data with regard to response intervals of 1195 out-of-hospital CA interventions where bystander CPR was performed and continued by the eight mobile intensive care units (MICUs) participating in the Belgian Cerebral Resuscitation Registry between 1982 and 1990. Partial correlations between time elapsed from CALL to CPR by lay public and outcome were determined when the effect of response times of 1st and 2nd tier were removed. The following groups were studied: ventricular fibrillation (VF), asystole and electromechanical dissociation (EMD), non-witnessed and witnessed. Good outcome was represented by initial restoration of spontaneous circulation (ROSC successes) and by prolonged survival (CPR successes) being 22.7 and 9.7%, respectively. The mean time +/- S.E.M. between CALL and CPR initiated by lay people for the studied population (n = 1195) was 2.5 +/- 0.1 min. The partial correlation coefficient between prolonged survival and time passed between CALL and bystander CPR was negative for all types of CA, yet significance was reached only in the non-witnessed group. Using ROSC as the endpoint significance is achieved in all groups except the VF patients, where the intervention times were shorter. In our population, prolonged survival was independently and negatively influenced by a delay between CALL and any CPR in the non-witnessed CA group (n = 421). PMID- 8351421 TI - The laryngeal mask in cardiopulmonary resuscitation in a district general hospital: a preliminary communication. AB - For a period of 13 months adult patients sustaining a cardiopulmonary arrest in the Royal East Sussex Hospital, Hastings, were attended by nursing staff and Operating Department Assistants (ODAs) specially trained in the use of the laryngeal mask (LM) as an airway adjunct. The LM was used 41 times in 40 patients. The LM failed on only two occasions, and was successful in three cases where endotracheal intubation proved impossible. No instances of aspiration were directly attributable to LM use. LM trained staff adopted its use enthusiastically, and skills acquired during training appeared not to fade over the period of the study. These results are considered to justify the performance of a large-scale trial of use of the LM in cardiac arrest patients. PMID- 8351420 TI - Effects of graded doses of epinephrine during asphxia-induced bradycardia in newborn lambs. AB - To study the hemodynamic effects of graded doses of epinephrine (EPI) in a newborn animal model of hemodynamically significant bradycardia, we performed the following study. Ten newborn lambs were chronically instrumented with catheters and flow transducers so that systemic, pulmonary arterial, left atrial and right atrial pressures as well as heart rate, cardiac output and left carotid artery flow could be monitored. During each of five asphyxia induced bradycardia episodes, with cardiac output depressed to approximately 30% of baseline, lambs were given either 0, 1, 10, 50, or 100 micrograms of EPI in a randomized sequence. After 30 s, the lambs were resuscitated with room air ventilation while hemodynamic parameters were monitored. During asphyxia and prior to EPI administration, all hemodynamic parameters were similar. In addition, for the first 30 s following EPI administration, hemodynamic parameters continued to deteriorate in a manner that was not influenced by the dose of EPI administered. During the resuscitation period with resumption of ventilation, systemic blood pressure and coronary perfusion pressure rose higher following 50 and 100 micrograms/kg of EPI than after the smaller doses. Heart rate was highest following the 100 micrograms/kg dose. Stroke volume and cardiac output, however, appeared to be blunted by the 100 micrograms/kg dose of EPI with no differences in carotid flow noted by dose of EPI administered. It appears that doses of EPI greater than 10 micrograms/kg, the dose currently recommended by the American Heart Association, may be beneficial as an adjunct in treatment of hemodynamically significant bradycardia. However, doses as high as 100 micrograms/kg may blunt cardiac output and stroke volume and should be used with caution. PMID- 8351422 TI - Tumor necrosis factor and monocytes are released during hemorrhagic shock. AB - Tumor necrosis factor (TNF) is a key mediator involved in many physiologic processes including immunity, inflammation, and metabolism. A relationship between TNF and hemorrhagic shock has not been clearly demonstrated. To help understand the role of TNF in hemorrhagic shock we developed a hemorrhagic shock model to measure TNF and monocyte levels during hemorrhage and resuscitation. Male Sprague-Dawley rats were anesthetized and subjected to a 50% blood loss (30 ml/kg) over 2 min and left in shock for 58 min. The animals were then resuscitated with two times blood loss (60 ml/kg) using lactated Ringers over 1 h. This model results in 75% mortality within 3 days (LD 75). Blood samples (2 ml) were obtained at intervals during shock and resuscitation, and assayed for TNF concentrations and white blood cell counts. Despite a marked fall in total leukocytes (24,600 pre-hemorrhage to 11,300 post-hemorrhage, P < 0.005), monocytes increased in percentage and in total count. Blood levels of TNF were initially undetectable but rose within 10 min after hemorrhage, peaked at 30 min after hemorrhage, and then became undetectable during resuscitation. In this model, macrophages and TNF are released into the circulation after hemorrhagic shock. TNF may play a role as a mediator in the pathophysiology of hemorrhagic shock. PMID- 8351423 TI - Corticosteroid supplementation during cardiac arrest in rats. AB - HYPOTHESIS: Corticosteroids will improve the rate of resuscitation from cardiac arrest. DESIGN: Prospective blinded randomized placebo-controlled trial. INTERVENTION: An 8-min cardiac arrest was induced by KCl infusion and chest restriction in 36 male Sprague-Dawley rats with continuous EKG and arterial blood pressure monitoring. At the start of CPR the rats received one of three study drugs: normal saline (placebo); 0.05 mg hydrocortisone (Group A) and 0.25 mg hydrocortisone (Group B). Mechanical ventilation, chest compressions and ACLS drug administration were provided following a standardized algorithm. RESULTS: The resuscitation rate was significantly higher (P < 0.05) in Group B (92%) compared to Group A (50%) and placebo (50%). For the rats resuscitated, the duration of CPR (placebo = 163 s, Group A = 126 s, Group B = 120 s) and the amount of epinephrine used (placebo = 0.007 mg, Group A = 0.005 mg, Group B = 0.005 mg) did not reach statistical significance (P = 0.15 and P = 0.21). CONCLUSION: Hydrocortisone significantly increased the rate of ROSC from cardiac arrest. There also appears to be a trend of decreasing duration of CPR and epinephrine requirements with hydrocortisone. Further studies evaluating the mechanism of action and long term effects of hydrocortisone in cardiac arrest need to be conducted. PMID- 8351425 TI - CPR and high dose epinephrine. PMID- 8351424 TI - Cardiopulmonary-cerebral resuscitation by using cardiopulmonary bypass through the femoral vein and artery in dogs. AB - Twenty-seven dogs, divided into three groups, were subjected to a normothermic ventricular fibrillation (VF) cardiac arrest of 15 min and resuscitated by using cardiopulmonary bypass through the femoral veins and artery (F-F bypass). Group I (n = 15): Cardiac beating did not return in any dogs during an initial 3-min conventional cardiopulmonary resuscitation, but it returned 5.2 +/- 3.8 min (mean +/- S.D.) after the successive initiation of the F-F bypass in all dogs, except in one with bypass trouble. Intermittent burst waves appeared on the electroencephalogram and continuous waves returned, 90.0 +/- 24.7 min and 130.7 +/- 28.1 min after the start of resuscitation, respectively. Values of blood glucose, lactate and potassium 5-15 min after the F-F bypass were significantly higher than those before induction of VF, while those of blood pH, base excess, hemoglobin, hematocrit, platelet and serum protein decreased significantly. Group II (n = 7): Both local cerebral (CBF) and myocardial blood flow (MCBF) returned to the pre-arrest level soon after the initiation of the F-F bypass, even though spontaneous cardiac beating was not yet restored. Closed or open chest cardiac massage could not produce as much blood flow as the F-F bypass did. In the early stage of restoration of spontaneous circulation, temporary interruption of the bypass led to a decrease in both local CBF and MCBF. Group III (n = 5): Spontaneous circulation was restored in all five dogs 5.2 +/- 1.1 min after the institution of the F-F bypass, which was continued for 164 +/- 30 min under mild hypothermia. After intensive care for a subsequent 6-36 h, the animals barked, moved their forelegs and could drink water. The mean neurological deficit score (normal: 0, brain death: 500) was 100.6. However, macroscopic examination of the brain in two dogs with prominent recovery revealed atrophy of the central gyrus and microscopic examination revealed injuries of the vulnerable neurons of the brain. PMID- 8351426 TI - Coma scales in paediatric resuscitation. PMID- 8351427 TI - [Histopathologic observations of restenosis following coronary angioplasty]. PMID- 8351428 TI - [The respiratory accessory muscles]. PMID- 8351429 TI - [Ischemic myocardium and remodeling]. PMID- 8351430 TI - [High altitude medicine and oxymeter]. PMID- 8351431 TI - [Control of the ventricular rate in atrial fibrillation]. PMID- 8351432 TI - [Clinical aspects of respiratory muscle fatigue]. PMID- 8351433 TI - [Selection of pacing mode (3)]. PMID- 8351434 TI - [Percutaneous cardiopulmonary support system (PCPS)]. PMID- 8351435 TI - [Effect of pilsicainide hydrochloride on atrial fibrillation threshold]. AB - To inventigate the electrophysiologic effects of pilsicainide hydrochloride on atrial fibrillation, we compared atrial fibrillation threshold (AFT), right atrial effective refractory period (RAERP), and inter-atrial conduction time (Inter-ACT) before and after the administration of pilsicainide in 12 patients with lone paroxysmal atrial fibrillation. The following electrophysiologic study was performed before and after the administration of the drug as the paced cycle length of 500msec. First, RAERP was measured. Secondly, Inter-ACT from the stimulating artifact to the initial deflection in the elecrocardiograms of the coronary sinus was measured. Thirdly, high-frequency (50Hz) stimulation was given at right atrial appendage continuously for one second just after the eighth basic paced beat. The stimulation current was increased by 1mA in a stepwise fashion from 2mA until atrial fibrillation ensued. AFT was defined as the lowest intensity of the current that induced atrial fibrillation or flutter of more than 30 seconds. Pilsicanide significantly increased AFT and Inter-ACT, but did not change RAERP. In conclusion, it is suggested that pilsicainide might decrease atrial vulnerability mainly by its effect on inter-atrial conduction delay and by the resulting increase in AFT. PMID- 8351436 TI - [A new device: a fenestrated sheath for IABP, which reduces the incidence of ischemia in the lower limbs]. AB - To decrease the incidence of ischemia in the lower limbs, we developed a new introducer sheath for IABP, which had 38 side holes (diameter; 1mm). Forty-five patients who received IABP counterpulsation support with this fenestrated sheath were compared with 108 patients in whom the ordinary nonfenestrated sheath was used. There was no significant statistical difference between these two study groups regarding age, height, weight and IABP insertion time. The frequency of ischemic episode of the lower limbs was 2.2% (one out of 45 patients) in the group with the fenestrated sheath, which was significantly lower than those with the ordinary sheath (18 out of 108: 16.7%) (p < 0.005). From these data, we deduced that this fenestrated sheath allowed more blood flow to the lower limb and was thus effective in preventing limb ischemia, particularly in patients with small caliber femoral arteries. PMID- 8351437 TI - [Early diagnosis and management of acute pulmonary embolism: clinical evaluation those of 225 cases]. AB - To contribute for making early diagnosis and treatment of acute pulmonary embolism (APE), we investigated on clinical pictures of 225 patients with APE. Common underlying factors were heart disease, prolonged bed rest, post-surgical state, thrombophlebitis, malignant tumor and post-catheterization state in this order. Dyspnea, chest pain, tachycardia and shock were frequently seen as initial symptoms and signs. Blood screening showed leukocytosis, hypoxemia, hypocapnia and elevated serum LDH. Electrocardiographic findings highly demonstrated were ST.T abnormalities, such as T inversion with ST elevation in V1-3, ST depression in V4-6 and sinus tachycardia. Chest X-rays showed diminished pulmonary vascular marking and pulmonary artery dilation. Right ventricular dilatation were frequently seen on 2-dimensional echocardiograms. Pulmonary artery pressure were elevated up to 49/20 (30) mmHg. Twenty-five percent of the patients died, and the recurrence was seen in 4%. Thus, as soon as APE is suspected by above clinical findings, definitive diagnosis should be obtained by the lung perfusion scan and pulmonary arteriography, then oxygen and thrombolytic agents should be given immediately to prevent the fatal outcome. PMID- 8351438 TI - [Cultured myocardial cell growth and hypertrophy by basic fibroblast growth factor]. AB - Basic fibroblast growth factor (bFGF) is a mitogen that is thought to play a important role in myocyte growth. In previous work, we found the increase of immunoreactivity of bFGF in cardiac myocyte of young SHR and pressure over loaded rat heart, and it suggested that endogenous bFGF which contained high molecular form of bFGF contributes to myocardial hypertrophy. To examine this hypothesis, rhabdomyosarcoma (A 204 cells) derived bFGF was used as wild type bFGF. Extracted bFGF from A 204 cells and nonserum conditioned medium of A 204 cells included high molecular form (22, 24 kd), as well as low molecular (18 kd) bFGF by western blotting, and showed hypertrophic effect in cultured myocardial cells. The hypertrophic effects were indicated in remarkable enlargement of cell size and significant increase in phenylalanine incorporation (x 2.2). The maximum expression of c-myc mRNA by A 204 conditioned medium was observed 30 min after stimulation, and it was also accompanied by an increase of accumulation of alpha skeletal actin mRNA by primer extension. After absorption of heparin binding growth factor from A 204 conditioned medium, it indicated no hypertrophic effects. In conclusion, it is likely that wild type bFGF including high molecular weight form plays a important role in cardiac myocyte growth and hypertrophy. PMID- 8351439 TI - [A case of sporadic and transient bradyarrhythmias in a patient with a glioma in the medulla oblongata]. AB - In a 20-year-old female patient with a brain stem glioma in the medulla oblongata in association with paraplegia and respiratory paralysis, bradyarrhythmias such as sinus bradycardia and sinus arrest repeated sporadically and transiently, but soon subsided as radiotherapy was being delivered to the glioma in the medulla oblongata. The bradyarrhythmias were differentiated from sick sinus syndrome in their sporadic and transient character. The patient responded normally to atropine, isoproterenol, and phenylephrine. Parasympathetic nerve reflexes induced by Aschner's, Czermak's, and Valsalva's maneuvers and sympathetic nerve reflex induced by change of body position were within normal limits. Although EKG abnormalities associated with diseases of the central nervous system are frequently due to intracranial hypertension and/or irritation of the hypothalamus, the bradyarrhythmias in this patient were possibly due to vagus stimulation caused by the glioma in the medulla. PMID- 8351440 TI - [Two adult cases with corrected transposition of the great arteries treated with permanent endocardial pacemaker implantation]. AB - [Case 1] A 32 year-old male had (I, D, D) type corrected transposition of the great arteries (cTGA) associated with ventricular septal defect and pulmonary stenosis. [Case 2] A 69 year-old male had (S, L, L) type cTGA associated with tricuspid regurgitation. Both cases showed advanced atrioventricular (AV) block due to HV block. Both patients had endocardial DDD pacemakers implanted, with no complication. (I, D, D) type cTGA is rarely accompanied with AV block, while the incidence of AV block is high in (S, L, L) type cTGA. We speculate that this results from the difference in the position of the AV node between these two types. PMID- 8351441 TI - [A case of infective endocarditis in which a new vegetation appeared on a different site during chemotherapy]. AB - 42-year-old man, who had been febrile for about a month, was admitted to our hospital. Laboratory testing showed leukocytosis and high titer of CRP. Streptococcus sanguis II was detected in his blood culture. According to the echocardiogram, he had a vegetation on the anterior mitral leaflet, so he was diagnosed as having infective endocarditis. Antibiotic susceptibility test using the disc method showed (3+) response to penicillin G. After intravenous administration of 20 million units of penicillin G for 3 weeks, a new vegetation appeared on the posterior mitral leaflet although the one on the anterior mitral leaflet had disappeared. Imipenem/cilastatin was administered until the acute phase reactants became negative. But the vegetation did not disappear, so he had vegetectomy. This is the first case report of infective endocarditis in which a new vegetation appeared on a different site despite the disappearance of the first lesion during chemotherapy. PMID- 8351442 TI - [A case of angiosarcoma presenting as ill-defined opacities on chest roentgenogram and hemothorax]. AB - A 74-year old male was referred to the Tokai University Hospital for evaluation of abnormal opacities on a chest roentgenogram. Laboratory tests demonstrated leukocytosis, elevated ESR and CRP, elevated LDH, and hypoxemia. The chest roentgenogram demonstrated several ill-defined nodular infiltrates on the bilateral upper lung fields. In addition, a CT scan revealed bilateral pleural effusion which was found bloody on diagnostic thoracocentesis. Administration of antibiotics failed to improve lung infiltration or laboratory data. The patient died of respiratory failure on the 23rd hospital day. At autopsy, multiple ill defined nodules, which were associated with alveolar hemorrhage, were scattered in the lungs bilaterally. Both hematoxylin-eosin and silver staining showed atypical cells of a vasoformative nature. Factor VIII related-antigen in the tumor cells was confirmed by the peroxidase-antiperoxidase method. These findings were consistent with angiosarcoma. The tumor foci were demonstrated in the lungs, pleura, kidneys, bone marrow, adrenal glands, and the gastrointestinal tract. The primary site of angiosarcoma, however, was not identified. Angiosarcoma, either primary or metastatic to the lungs, should be included in the differential diagnosis of multiple ill-defined nodular opacities associated with hemothorax. PMID- 8351443 TI - [A case of chronic hepatitis C complicated by ischemia-like changes seen on the electrocardiogram during interferon treatment]. AB - A 53-year-old woman was admitted to the hospital for chest pain with headache, nausea and vomiting, two and a half hours after an intramuscular injection of 6 x 10(6) units of IFN (interferon) alpha 2a, in the 11th week of IFN treatment for chronic hepatitis C. The electrocardiogram (ECG) showed ST depression and T inversion in leads II, III, aVF and V3-V6, as commonly seen in myocardial ischemia. However, emergency coronary angiography (CAG) did not show stenosis or spasms clearly, serum CPK was always within the normal limits, Tc-99m PYP scintigraphy and T1-201 scintigraphy did not show any abnormal uptake or defect, and the echocardiogram did not show any abnormality. She recovered from chest pain and the ischemia-like changes seen on the ECG, after IFN treatment was stopped, and she rested for 7 days from this treatment and other treatment using nitrites and a calcium-antagonist. After recovery, the ECG during exercise and hyperventilation showed changes similar to those seen on admission. From these findings, this case was considered to be precipitated by spasms of coronary microvessels, which were not noticeable in CAG. The cause was thought to be complicated by IFN treatment, because this episode appeared after IFN injection, and improved after stopping IFN treatment. PMID- 8351444 TI - Surfactant apoprotein A secretion by human tracheobronchial epithelial cells. AB - To determine whether surfactant apoproteins are produced locally by the airway walls, we used a two-site simultaneous immunoassay with monoclonal antibodies and measured the surfactant apoprotein-A (SP-A) content in media cultured with human airway explants or cultured epithelial cells. Tracheobronchial explants were cultured for 2 successive periods (periods I and II). Significant SP-A concentrations were detected in both periods. Methacholine (MCh) or isoproterenol (ISP), added to the medium at the beginning of period II, reduced the ratio of SP A concentration in period II to that in period I, compared to samples without treatment. The SP-A concentration in the medium at the confluent period of cultured epithelial cells was significantly higher than at the mid-period, indicating that SP-A secretion is dependent on the cell number. The supernatant from explants stimulated by MCh was capable of reducing SP-A secretion from cultured epithelial cells. Immunohistochemical study of SP-A using monoclonal antibody demonstrated positive immunoperoxidase staining in the cytoplasm of epithelial cells. Further, Western blots of electrophoresed proteins from epithelial cells showed the characteristic properties of SP-A. These findings indicate that tracheobronchial epithelium can secrete SP-A. PMID- 8351445 TI - Dynamics of the ventilatory response to hypoxia in humans. AB - Dynamic responses of the ventilatory system to rapid variations in isocapnic hypoxia were studied in five subjects. Sawtooth-shaped inputs were presented at constant amplitude with periods of 120, 90, 60, 45 and 30 sec, and square-wave inputs at different amplitudes with periods of 120, 60 and 30 sec. A breath-by breath model fitting technique was used to assess whether any of a number of first order models of hypoxic ventilatory dynamics could fit the data adequately. The following was found: 1) An equation for the desaturation of haemoglobin provided a better expression for hypoxia in the model than did a hyperbolic function of PO2. 2) The gain and/or offset model parameters varied significantly between experiments, but the time constant and pure delay terms did not. 3) The time constants, and to a lesser extent the pure delays, were found to vary significantly between sawtooth experiments of different frequencies. The failure of a single set of dynamic parameters to describe all the responses suggests that the model is incomplete. 4) There was significant asymmetry in the hypoxic response with the on-transient dynamics faster than the off-transient dynamics. The results of the model fitting study suggest that a first order model cannot fully describe the hypoxic ventilatory dynamics. PMID- 8351446 TI - Latency of the ventilatory chemoreflex response to hypoxia in humans. AB - Latencies for the ventilatory response to hypoxia have been estimated from data from experiments in which square waves of isocapnic hypoxia (periods 30 sec and 60 sec) were presented to 5 subjects. Distorted steps were excluded from the analysis, and the remaining steps were time-aligned relative to the step and then averaged. For the 30 sec data, the median latency for the response to the step into hypoxia was 1 breath or 5.1 sec (time to mid-point of first significantly different breath) and for the step out of hypoxia was 1 breath or 4.7 sec. The number of transients analyzed averaged 87 per subject per transition type. For the 60 sec data, the median latency for the step into hypoxia was 2 breaths or 6.8 sec, and for the step out of hypoxia was 2 breaths or 6.0 sec. The number of transients analyzed averaged 40 per subject per transition type. These latencies are generally shorter than those reported previously and suggest that the ventilatory variability may have served to lengthen the measured latency of response in previous studies. PMID- 8351447 TI - Ventilatory response to exercise after heart and lung denervation in humans. AB - This study, aimed at investigating some aspects of breathing control at work, was conducted on 8 heart and lung transplant recipients (HLTR) (age 33 +/- 13 years, mean +/- SD; 10 +/- 6 months post-transplantation) and on two control groups, i.e. 11 heart transplant recipients (HTR) and 11 healthy untrained subjects (C). The patients performed a series of 2 to 6 1-min exercise bouts (at 25 or 50 W, corresponding to about 50% of their VO2max) on a bicycle ergometer, followed by a 5 min 25 or 50 W constant load. C exercised both at 50 W (C1) and at 50% of their VO2max (C2). Inspiratory (VI) and expiratory (VE) ventilation, tidal volume (VT), respiratory frequency (fR), end-tidal O2 and CO2 partial pressures (PETO2 and PETCO2 and gas exchange (VO2 and VCO) were measured breath-by-breath. "Phase I" ventilatory response (ph I) was determined as the mean changes of VI, VE, VT, fR, PETO2 and PETCO2, compared to rest, during the first two respiratory cycles following exercise onset. In HLTR ph I did not significantly differ from that of C1 and C2, whereas the response was lower in HTR. VE, VO2 and VCO2 responses during "phase II" (t 1/2 on-) and "phase III" (steady state exercise) were similar in HLTR and in HTR. t 1/2 on- were longer in HLTR and in HTR compared to C1. In 3 HLTR the ventilatory pattern during the 5 min constant loads was similar to that of HTR and C, whereas 4 HLTR presented higher VT and lower fR values. It is concluded that: 1) The ventilatory response to exercise, in all its phases, is substantially preserved despite lung denervation. When slight alterations are found (i.e. the slower phase II), they are presumably of peripheral origin. 2) The normal ph I in HLTR indicates that cardiac and/or pulmonary inputs to the respiratory centers are not involved in its regulation, or that their role can be subserved by other ventilatory control mechanisms. PMID- 8351448 TI - Ventilation is coupled to metabolic demands during progressive hypothermia in rodents. AB - We examined changes in ventilation and metabolic rate during hypothermia (36-27 degrees C) induced with exposure to helium-oxygen and cold in halothane anesthetized ground squirrels (Spermophilus lateralis) and rats. As a consequence of proportionate decreases in VCO2 and breathing frequency, the VE/VCO2 in both species remained constant. The changes which occurred in breathing pattern were also similar in the two species; an increase in TI and TE along with emergence of apneic periods between breaths at body temperatures below 31 degrees C. VT/TI and TI/TTOT decreased but VT remained constant with progressive hypothermia. The ventilatory responses to hypercapnia and hypoxia decreased to the same extent as the ventilatory and metabolic requirements in the ground squirrel but not the rat. The changes in VE and VCO2 during hypothermia in the ground squirrel predicted well the values observed in deep hibernation. We conclude that regulation of ventilation at reduced body temperatures is tightly coupled to metabolic demand. PMID- 8351449 TI - Frequency of mechanical ventilation and respiratory activity after double lung transplantation. AB - We investigated the contribution of pulmonary afferent nerve fibers to the control of inspiratory activity in awake humans. Eight double lung transplant outpatients and eight normal subjects were hyperventilated with a mechanical ventilator. Respiratory frequency was increased until no respiratory activity was detectable. Then, by either adding CO2 in the inspired gas or decreasing respiratory frequency, end-tidal PCO2 (PETCO2) was increased until inspiratory activity (i.e. change in inspiratory airway pressure peak and/or time profile) was detected. In normal subjects, PETCO2 threshold for inspiratory muscle recruitment was significantly lower when frequency was decreased than when CO2 was added (31.3 +/- 6.8 Torr vs. 38.2 +/- 8.1 Torr respectively, P < 0.005). This was not the case in the double lung transplant group (31.5 +/- 6.5 Torr vs. 32.9 +/- 5.8 Torr). These findings suggest that pulmonary afferent nerves have an inhibitory effect on inspiratory activity in humans. PMID- 8351450 TI - Limitations to VO2max in humans after blood retransfusion. AB - Seven young, healthy male subjects performed maximal exercise on a cycloergometer with central venous and arterial catheters, before and after autologous retransfusion of red blood cells. Maximal oxygen consumption (VO2max), blood gas composition and haemodynamic variables were measured, in order to test the hypothesis of monofactorial vs. polyfactorial VO2max limitation. Autologous blood retransfusion led to significant increases in haemoglobin concentration and consequently arterial oxygen concentration during maximal exercise, while maximal cardiac output, heart rate and stroke volume were not significantly changed. The relationship between maximal oxygen delivery (cardiac output.arterial oxygen concentration; (Q.CaO2)max and maximal oxygen consumption in this study was VO2max (L.min-1) = 0.02 + 0.64.(Q.CaO2)max (L.min-1), the slope being significantly less than unity. These results suggest that (Q.CaO2)max plays but a fractional role in limiting VO2max, in agreement with recent models concerning the resistance to oxygen flow in the respiratory system (di Prampero and Ferretti, Respir. Physiol. 80: 113-128, 1990). The relative increase in VO2max after blood retransfusion matched the relative increase in 'aerobic performance', measured as the maximal power output that could be maintained aerobically for 30 min. Furthermore, the increase in maximal power output (15 +/- 3 watts) could account for almost all of the extra oxygen consumption. This match suggests that there is an inability to fully utilize muscle oxidative capacity in the normocythaemic state. PMID- 8351451 TI - Thyroid function in critical illness and burn injury. PMID- 8351454 TI - Nutrition in burn patients. PMID- 8351453 TI - Metabolic response to burn injury: nutritional implications. PMID- 8351452 TI - Pulmonary function in the burn patient. PMID- 8351455 TI - White blood cell response to burn injury. AB - Multiple sites of decreased immune response have been discovered, but the instigation of this diffuse immunosuppression remains a matter of much debate. Several investigators have observed immunosuppressive affects of low-molecular weight peptides found in the serum of burn and trauma patients. These substances have been termed suppressive active peptides (SAP). Current research is also focusing on the intricate connection between stress hormones and neurotransmitters, in which there exist a complex information channel between the immune, endocrine, and central nervous systems. It is becoming clear that immune homeostasis may require regulatory influence via immunocompetent cells, along with influences from the central nervous system and a balanced endocrine environment. In fact, macrophages, lymphocytes, and neutrophils contain receptors for many hormones including corticosteroids, insulin, growth hormone, catecholamines, acetylcholine, and endorphins. The dramatic alteration in the hormonal milieu after injury may play a significant role in immunocompetence. Attempts to modulate specific defects in the immune system have been unsuccessful to date. Our goal, to decrease the risk of infection in burn patients, therefore, is meticulous supportive care. This includes not only reducing the risk of invading bacteria, but also increasing the patient's resistance to overall infection. The cornerstone of this support is to restore mechanical barrier function to as near normal as possible. Immediately after injury, vigorous wound management includes several daily debridements combined with wound protection using an appropriate topical antimicrobial substance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351456 TI - Bacterial translocation in burn injury. PMID- 8351457 TI - [Ovarian cysts. Diagnostic and therapeutic aspects]. AB - The methods used to carry out exeresis of ovarian cysts by celioscopy are now familiar. Today, the main concern is the selection of annexial tumors appropriate for celiosurgical treatment in order to limit their use to benign organic cysts only. By comparing the results of a sery of 200 cysts which were treated surgically with cases in the literature, the authors conclude that the three pronged use of clinical, ultrasound and macroscopic data in the diagnosis of malignant tumors is reliable. Progress remains to be made however in identifying functional cysts which are sometimes mistaken for an organic structure and all too often are still dealt with surgically. In order to reduce the incidence of such errors, new perspectives are envisaged, knowing that diagnostic error is often related to change in their ultrasound structure or their persistence despite conventional estro-progestogen treatment. PMID- 8351459 TI - [Retroplacental hematoma and uterine Doppler scan]. AB - The authors studied uterine Doppler findings in four cases of retroplacental hematoma at 26, 30.5, 31 and 37 weeks of amenorrhea. In all cases, the diastolic index was low, and a diastolic notch was present. In three cases, the hematoma was visualised under ultrasound. The literature on the subject confirms that the velocity of the uterine circulation is always abnormal in retroplacental hematoma. This test is therefore fundamental for the detection of clinically incomplete retroplacental hematomas and for determining the pregnancy prognosis in women with a history of vascular problems. Two of our patients received treatment with acetylsalicylic acid at an early stage of a subsequent pregnancy. The uterine Doppler scans carried out during this pregnancy at the same date as during the pregnancy with retroplacental hematoma revealed normal bloodflow velocity. The infants were born at term with normal weight. Uterine Doppler ultrasound is, therefore, an essential prognosis factor for these high-risk patients. In addition, routine performance of a uterine Doppler scan at about 22 weeks of amenorrhea in women in their first pregnancy could be useful, as any abnormal finding might be the indication for preventive treatment with acetylsalicylic acid. PMID- 8351458 TI - [Plea for quality cytological specimens in the screening of cervical cancer]. AB - In the context of a typical false negative cervical cancer test, the authors discuss the value of such screening tests and the various causes of a lack of success. A poor sample is the main cause of false negatives, and therefore involves everyone taking part in the procedures for this screening test. PMID- 8351460 TI - [Diurnal variation of active movements: an indication of fetal hypotrophy?]. AB - In a prospective study of 36 pregnancies, the authors made use of the mother's counting of active movements in order to evaluate the correlation between daytime fluctuations in active movements and fetal hypotrophy. With a threshold peak mean evening motor activity no more than 20 p. cent greater than in the morning throughout the period counted, daytime variations were found to have optimal diagnostic capacity for hypotrophy. During the last week preceding delivery, a threshold mean peak evening active movements no more than 35 p. cent greater than in the morning yielded optimum diagnosis of fetal hypotrophy. Furthermore, there was a correlation between daytime fluctuations in active movements and the findings of fetal ultrasound biometry and utero-umbilical flow velocimetry. PMID- 8351461 TI - [Placenta percreta over a cesarean scar with bladder invasion. General review and 2 case reports]. AB - The authors report two new cases of placenta percreta on a caesarian scar with invasion of the bladder. On the basis of a review of the literature, they demonstrate its seriousness, which is always increased by the unexpected nature of the complications. They therefore recall the clinical and paraclinical factors which can provide grounds for suspecting this possibility, so that the hemostasis hysterectomy required can be carried out on the best possible conditions. PMID- 8351462 TI - [Bladder pheochromocytoma and pregnancy. A case report]. AB - The authors report the case of a 31-year old patient who successfully completed a pregnancy despite unsuspected bladder pheochromocytoma. After delivery, the patient required care post-partum due to serious hemodynamic problems. Hypertension had been attributed to toxemia of pregnancy. The authors recall the diagnostic difficulties of tumors of this type, and the means which can be used for topographical diagnosis and the precautions to be taken before this tumor can be treated surgically. PMID- 8351463 TI - [Doctor Pascal Rougon. An imaginary predecessor]. AB - Through the Rougon-Macquart series and the cases described in the last volume (Le Docteur Pascal, 1893), clinical analysis of the 58 characters identifies only seven neurotics and six alcoholics (only three of whom were Rougon-Macquart by birth). All the other illness described are unrelated to hysteria in the family. It remains true, however, that Zola's interpretation of hereditary degeneracy follows that of contemporary medical teaching, as witnessed by the genealogics published by Charcot in 1893. Through the voice of Dr. Pascal, however, Zola does challenge the concepts of heredity advanced by his medical advisors: he envisages the concepts of dominance and recessiveness without devising any general scheme for the transmission of hereditary characteristics, but eight years before Vries he advanced the idea of mutations, which he interprets as accidents occurring at the beginning of the ovum's development. When faced by the lack of success of his opotherapy of degenerative diseases, Pascal initiates trials versus a placebo and puts forward a highly coherent theory of what we would now call the placebo effect. It appears, therefore, that contrary to the opinion of most commentators, Emile Zola was in fact capable of a remarkable subtleness when he ventured into medicine. Through Dr Pascal Rougon, and notwithstanding the mockery of Flaubert, Goncourt and France (and of many others), he was a brilliant trail-blazer in the fields of genetics and therapeutics. Six years later he was to strike again with Dr Boutan, who invented what we now know as the prophylactic care of mothers and children (Fecondite, 1898). PMID- 8351464 TI - Crystalluria and its possible significance. A patient-control study. AB - The significance of crystalluria in the diagnosis and prognosis of urolithiasis remains a controversial subject in the current urological literature. In this study, in addition to the standard urolithiasis clinical and biochemical work-up, routine urine microscopy was performed to study crystals in 1 fresh and 2 stored morning urine samples from 140 urinary stone patients and 42 controls. Crystalluria was more frequently detected in patients (9.3% of the fresh samples) than in controls (2%). Storing the samples for 6 hours did not increase the frequency percent of detected crystalluria either in patients or controls. However, in the samples stored for 24 hours, the frequency of crystalluria increased to 27.1% in patients and only to 12% in controls, though the pH did not change from that of the fresh sample. In addition, while calcium oxalate crystals in patients formed aggregates whether in fresh or 24 hour samples, those of controls did not. This denotes a characteristic change in the physico-chemical properties of the urine of stone formers from that of controls. Accordingly, the study of crystalluria in patients with urolithiasis seems to help in the proper evaluation and, maybe, treatment of the disease. PMID- 8351466 TI - Ionic associations within 460 non-infection urinary stones. A quantitative chemical analytical study applying a new classification. AB - In addition to standard quantitative wet chemical and inductively coupled plasma atomic-emission spectrometric stone analytic techniques, elemental analysis for the determination of nitrogen, carbon and hydrogen was utilized in this study of 460 category I (non-infection) urinary stone samples from western Saudi Arabia. They were classified according to the percentage composition of detected ions, including trace or minimum amounts. The incidence of uric acid stones (24%) is higher than that reported from western countries but similar to those reported from eastern Europe and other parts of the middle east and most are in the group with the highest uric acid content (UrI4). Oxalate stones are the most common type (61%) and phosphate stones (15%) the least common. The results confirm the reliability of elemental microanalysis and support its use for the quick identification of stones especially those that weigh < 1 mg and are too small for wet chemical analysis. Within the various stone types, however, the ionic associations shown by wet chemical analysis denoted the presence of mutual indirect associations between the characterising ion oxalate and both uric acid and phosphate ions, but no association between the characterizing ion uric acid and phosphate ions. Factors that affect these ionic correlations may influence the processes of stone initiation and type of stone formed. PMID- 8351465 TI - Stone recurrences in kidneys made stone-free by percutaneous extraction. AB - Of 100 renal units which were made stone-free by percutaneous stone extraction in 1985, 86 (86.0%) were re-examined radiologically up to 5 years after operation. The re-examination was performed because of symptoms or as part of a regular check-up or after calling the patient. Intrarenal calcifications were diagnosed in 27 of 86 (31.4%) of the renal units, but only in 11 (12.8%) were there stones requiring treatment. PMID- 8351467 TI - Influence of Escherichia coli on urease-induced crystallisation in human urine. AB - Urease was added to urines inoculated with Escherichia coli 24 hours earlier and to control urines not inoculated with E. coli. The inoculation did not change the concentration of the measured urine components. The urease-induced ammonium ion production and pH increase was reduced in E. coli-inoculated urines compared to control urines. This suggests that E. coli can inhibit urease. The precipitation of both phosphate and magnesium on glass rods inserted in the urine was reduced with 40-50% in the E. coli-inoculated urines. The results demonstrate that E. coli can influence urease-induced crystallisation. PMID- 8351468 TI - The distribution of estrogen receptors in the urinary tract of the male rabbit. An immunohistochemical and biochemical study. AB - The distribution of estrogen receptors (ER) in the urinary system in the male rabbit were investigated in 18 mature and healthy rabbits by immunohistochemical examination of tissue samples taken from renal pelvis, mid-ureter, bladder-top, posterior urethra and the prostate. ER were detected in 17 out of 18 cases in the urothelial lining and the subepithelial stromal cells of the posterior urethra; and in 15 out of 18 cases in prostatic stromal cells. ER was not found in bladder top, mid-ureter or renal pelvis. Receptor determination in the isolated cytosolic and nuclear fraction, showed that the mean prostatic receptor density were 151.5 f mol/mg protein in the nuclear and 51.4 in the cytosolic fraction. The corresponding mean values obtained from the posterior urethra were 128.2 and 88.9 f mol/mg protein. We conclude, that ER can be demonstrated in the urinary system of the male rabbit, and these are restricted to the posterior urethra and the prostatic stromal tissue. PMID- 8351469 TI - Effects of unilateral pelvic ganglionectomy on urinary bladder function in the male rat. AB - Micturition interval and micturition volume were measured in water loaded male rats before and up to 6 weeks after unilateral pelvic ganglionectomy. There was no effect on micturition interval until 7 days after the ganglionectomy. Micturition interval then remained increased. Maximal micturition volume was higher than in the control group from 4 to 14 days after surgery. Cystometrograms were recorded 12 days or 6 weeks after surgery. At 12 days the micturition pressure was lower in the unilaterally ganglionectomized than in the controls. After 6 weeks there was no significant difference in micturition pressure. A reduction of micturition pressure by about 50% was observed after i.v. injection of atropine, but no residual urine developed. Electron microscope investigation showed a considerable decrease in number of nerve terminals on the ganglionectomized side 3 days after surgery. Most of them were devoid of synaptic vesicles. On the contralateral side the majority of nerve terminals appeared normal, but many had a decreased number of vesicles. After 14 days the number of terminals was still lower than normal on the ganglionectomized side. They generally contained only a small number of vesicles. Also, on the contralateral side some nerve endings with the reduced complement of vesicles were found. We suggest that the effects of unilateral ganglionectomy on micturition volume and interval can be explained by a decreased sensory input from the bladder and that the effect on micturition pressure is due to a transient decrease in number and function of motor nerve terminals in the detrusor muscle. PMID- 8351470 TI - Verrucous carcinoma of the bilharzial bladder. Impact of invasiveness on survival. AB - Verrucous carcinoma of bilharzial bladder, a rare neoplasm, is regarded as a distinct variant of squamous cell carcinoma. We studied 37 cases treated with cystectomy in the past 15 years. Despite previous reports of no local invasion and no local recurrence or distant metastasis postoperatively, we observed 60% of focal tumour transformation into invasive squamous cell carcinoma. Such transformation and dedifferentiation to squamous cell carcinoma can be expected in a high proportion of these tumours. The survival rate in the invasive cases was approximately the same as in squamous cell carcinoma. Non-surgical management or adjuvant treatment to surgery are inappropriate in verrucous bladder carcinoma. Radical cystectomy is the only standard treatment offering cure. PMID- 8351471 TI - Staging of bladder carcinoma by computer tomography-guided transmural core biopsy. AB - In an attempt to improve staging of bladder cancer, computed tomography-guided transmural core biopsy was performed in 17 patients. In the first four patients a 0.9 mm cutting needle was used. This small needle yielded easily fragmented cores and consequently the remaining biopsies were taken with a 1.2 mm needle with an improved result. In all but one case sufficient histological material to allow a diagnosis was obtained by the core biopsy technique. Transmural tumor infiltration, as verified in corresponding cystectomy specimens, could be identified more often with the core biopsy than in biopsies obtained by transurethral resection. False negative diagnosis occurred when the tumor was not clearly visible on the computed tomography scan. No short-term side effects of clinical importance were found with the procedure. PMID- 8351472 TI - A study of prognosis and clinicopathology of bladder cancer to blood group type of host patients in Japan. AB - A total of 538 patients with transitional cell carcinoma of the bladder with a mean follow up period of 5.8 years (range 1-25) were retrospectively analysed to see if there were any associations between blood group and grade, stage, or prognosis of the tumour. In contrast to previous findings among European and Americans, there were no significant differences among blood groups for stage, histological grade, or survival rate. PMID- 8351473 TI - Prognostic factors in nodular transitional cell bladder tumours. AB - A cohort of 106 nodular transitional cell bladder cancers (TCC) were followed up for a mean of 9 years. Clinical stage, WHO grade, six morphometric nuclear factors and volume corrected mitotic index (M/V index) were correlated to progression and survival during the follow-up period. Nuclear factors were related to WHO grade with a borderline significance (p = 0.01-0.3) whereas the M/V index showed a highly significant relation to WHO grade. Neither nuclear factors nor the M/V index were related significantly to T-, N- or M-categories at the time of diagnosis. Progression in N- and M-categories was related independently to WHO grade whereas progression in T-category could not be predicted significantly by none of the variables included in this analysis. Survival was predicted by T-category (p = 0.0028), N-category (p = 0.0001), M category (p = 0.0057) and M/V index (p = 0.010). In T1-T2N0M0 tumours survival was predicted by the Dmax (p = 0.015) and by the M/V index (p = 0.039). In multivariate survival analysis T-category (p < 0.001) had independent prognostic value. In T1-T2N0M0 tumours only the M/V index predicted survival independently (p = 0.007). The results show that only the proliferation rate in addition to T category have prognostic significance in nodular TCC. PMID- 8351474 TI - Extraperitoneal pelvioscopy in staging of bladder carcinoma and detection of pelvic lymph node metastasis. AB - This study was carried out to examine the efficacy of extraperitoneal pelvioscopy in detecting pelvic metastasis in patients scheduled to undergo radical cystectomy without preoperative chemo- or radiotherapy. The results of pelvioscopy were compared with those obtained by laparotomy. 54 consecutive patients underwent pelvioscopy without complications. Three were technically insufficient. Lymphatic tissue was biopsied in 29 (54%). Pelvioscopy demonstrated tumor dissemination in 5 patients (9.3%): 2 had pT4b tumor, 2 pelvic nodal metastases and 1 both. The remaining 49 patients with benign pelvioscopy were scheduled for laparotomy but 7 patients did not undergo the procedure: 3 had extrapelvic metastasis, 1 bronchial carcinoma, 1 aortic aneurysm, 1 refused surgery and 1 had pulmonary insufficiency. Accordingly, 42 patients underwent open exploration which demonstrated pelvic metastasis in 11: 9 had nodal metastasis, 1 a pT4b tumor and 1 both. Consequently the sensitivity of pelvioscopy in detecting pelvic metastasis was calculated at only 31%. This result indicates that extraperitoneal pelvioscopy should be considered a screening procedure rather than an accurate staging procedure for pelvic metastasis. PMID- 8351475 TI - Laparoscopic lymphadenectomy. Preliminary experience. AB - Pelvic lymphadenectomy is a well established method for staging carcinoma of the bladder and prostate. Usually it is done by open surgery, but we now report preliminary experience with the laparoscopic approach. The technique is described in detail, and the results seem to indicate that the procedure is safe, has few complications and gives less pain than open surgery, with rapid recovery and early postoperative discharge from hospital. PMID- 8351476 TI - Radical retropubic prostatectomy for localised prostatic carcinoma: a clinical and pathological study of 201 cases. AB - To examine the role of radical retropubic prostatectomy in clinically localised prostatic cancer we reviewed a series of 201 patients all of whom had undergone bilateral pelvic lymphadenectomy. Frozen section showed metastatic pelvic lymph nodes in 13 cases and 6 cases were too locally advanced for operation; prostatectomy was done for the remaining 182. The pathological staging was based on examination of sections of the whole organ. In 109 (60%) the carcinoma was confined to the prostate gland or to the specimen, in 46 (25%) there was carcinomatous growth in the surgical margin, and in 27 (15%) there was invasion of the seminal vesicles. The Gleason score was significantly higher in cases with involvement of the surgical margin or seminal vesicles. There was one operative death (of pulmonary embolism), and the postoperative cardiovascular morbidity was 7%. The incidence of wound infection was 6%, and there were two rectal injuries and three symptomatic lymphoceles. A total of 135/170 evaluable patients (79%) were completely continent postoperatively, and only two developed severe incontinence. Erectile potency was preserved in 24 of 126 (19%). We conclude that radical retropubic prostatectomy is safe and that the complication rate is acceptable. The completeness of the tumour excision seems to be associated with the pathological grade of the tumour. PMID- 8351477 TI - Age as a prognostic variable in patients undergoing transurethral prostatectomy. AB - In a retrospective study the outcome of transurethral prostatectomy (TURP) for benign prostatic hyperplasia (BPH) in patients more than 80 years old was compared to a control group of patients with a mean age ten years younger. The elderly had significantly more tissue resected and presented with a higher rate of preoperative urinary tract infection. More urological complications were seen among the elderly but these were generally short lived and had no influence on the morbidity, mortality and symptomatic outcome. The perioperative mortality was 3.2% among elderly and 0% in the younger age group. A cardiorespiratory risk score could not predict patients at risk. In conclusion the age per se had no major influence on the outcome of TURP. PMID- 8351478 TI - Urethral stricture repair: results in 179 patients. AB - From 1977 till April 1990 169 operative reconstructions of urethral strictures were carried out in this clinic. 49 patients with a short stricture (less than 2 cm) underwent excision and end to end anastomosis. In 18 patients with a long stricture (2-6 cm) one stage urethroplasty with a transverse distal penile or preputial island of skin flap was used. 102 patients with extensive or otherwise problematic strictures were subjected to two-stage mesh skin graft urethroplasty. In 10 patients with a short stricture we have recently implanted a new urethral stent in the strictured area after visual urethrotomy. During a long-time follow up a good anatomical and functional result was achieved in all but 2 patients who underwent an excision and end to end anastomosis. In the island flap urethroplasty group a restricture occurred in one patient, and mesh graft urethroplasty was successful in all but 3 patients. In the urethral stent patients the primary results are excellent. PMID- 8351479 TI - The "Wallstent": a new stent for the treatment of urethral strictures. AB - Ten patients have been reviewed in whom urethral stents were implanted for treatment of urethral stricture. Their urethral strictures had been treated with a median of 4.2 endoscopic urethrotomies under direct vision without success. The patients were first treated with optical urethrotomy, and dilatation to 30 F- after which the stents were inserted under direct endoscopic control. A total of 12 stents were inserted. All patients had a 30 mm stent inserted first, and two patients had an additional 20 mm stent inserted because of recurrent stricture at the distal or proximal end of the first stent. One patient had a urethrotomy 12 months after insertion of the stent because of a short recurrent stricture at its distal end. The median length of follow up was 24 months. The median preoperative maximum flow rate was 6.5 ml/s, and the median postoperative maximum flow rate was 20.3 ml/s. Half the patients had postmicturition dribbling postoperatively. The stents were covered with epithelium after 6-18 months, most between 12 and 18 months. PMID- 8351480 TI - Balloon dilatation of ureteral strictures. AB - Balloon catheter dilatation is now an accepted method for treating strictures of the upper urinary tract. A successful result was obtained in 34 (85%) of 40 patients with symptomatic stricture. The number of dilatations required for improved runoff from the kidney was one in 26 cases, two in six cases and three in one case. One patient had a permanent stent and six required a conventional operation. There were seven recurrences of stricture, all within 4 months after the dilatation. One of these patients required nephrectomy because of nonfunctioning kidney. PMID- 8351481 TI - Adenocarcinoma of the renal pelvis in an elderly woman. AB - Adenocarcinoma of the renal pelvis is so rare that many reviews of renal tumours fail to include any instance of this lesion. We present a 75-year-old female patient with no previous history of urological disease in whom a renal pelvic tumour was diagnosed. Histological examination after radical nephroureterectomy proved the tumour to be a rare adenocarcinoma. The course of the disease, the possible predisposing factors, the treatment of the tumour and the prognosis are discussed. PMID- 8351482 TI - Restoration of function of a renal allograft by percutaneous transluminal angioplasty of an intrarenal vessel. PMID- 8351483 TI - Medial fibroplasia: involvement of renal artery and small renal arteries in renal vascular hypertension. AB - Dysplasia of the renal artery may cause renal vascular hypertension. The most common type of dysplasia is the medial fibroplasia. Medial fibroplasia, as well as the other types of dysplasia, has only been described in the main and primary branches of the renal artery. A case of medial fibroplasia, where arterial changes were seen far out in the small renal vessels is reported. PMID- 8351484 TI - Hyponatremia, hyperkalemia and hypercalcemia after ileal conduit diversion. AB - In all types of urinary diversion interchange of electrolytes between blood and the urine in the lumen of the conduit may occur, resulting in electrolyte abnormalities. We describe a 67-year-old woman who developed hyponatremia, hyperkalemia and hypercalcemia following ureteroileocutaneostomy. The hyperkalemia and hypercalcemia were successfully treated with sodium polystyrene sulfonate. PMID- 8351485 TI - Eosinophilic cystitis simulating invasive bladder carcinoma. AB - A case of eosinophilic cystitis simulating an invasive bladder carcinoma is reported. The disease had a subacute course and was associated with arthritis of the symphysis pubis and both sacroiliacal joints. PMID- 8351486 TI - Bladder stone: a complication of intravesical migration of Lippes loop. AB - We report on a woman in whom an intrauterine contraceptive device (Lippes loop) migrated from the uterus to the bladder with formation of a calculus. Eight years elapsed between intrauterine insertion of the device and its retrieval with the calculus from the bladder. PMID- 8351487 TI - Prostatic abscess. A review of literature and a presentation of 5 cases. AB - Abscess of the prostate has become increasingly rare due to modern antibiotics and a decreasing incidence of gonococcal infections. It is still difficult to diagnose the disorder on clinical grounds. Ultrasound examination is recommended. The preferred treatment is nowadays transurethral prostatic resection. We report 5 cases from a urologic department, during a period of 12 years. PMID- 8351488 TI - Y-autosome translocation associated with azoospermia. AB - Y-autosome translocation is a rare condition. We report here a case of balanced Y autosome translocation associated with azoospermia. Nineteen cases of a balanced Y-autosome translocation associated with azoospermia are reviewed, and hormone condition and testicular histology are discussed. PMID- 8351489 TI - Stimulation of early bone formation by the combination of an osteopromotive membrane technique and hyperbaric oxygen. AB - Large bone defects often heal incompletely as a result of ingrowth of connective tissue. By using a mechanical hindrance, a porous expanded polytetrafluoroethylene (e-PTFE) membrane, it is possible to prevent fibroblasts and other soft connective tissue cells from entering the defect, thereby allowing osteogenesis to occur unhindered. As evidenced in several investigations, this osteopromotive membrane technique causes a strongly improved bone regeneration of well defined osseous lesions. Hyperbaric oxygen treatment has also been shown to accelerate bone healing. In this study the value of combining the two techniques was investigated. Through-and-through bone defects, 5 mm in diameter, were produced unilaterally in the angular region of the mandibles of adult rats (n = 60); the defects in half the number of animals were covered lingually and buccally with membranes. The animals were then divided into four groups: treatment with membrane alone, treatment with hyperbaric oxygen alone, combined treatment, and no treatment. Histological examination of the defects after 14 days showed that the combination of techniques had resulted in significant improvement in bone healing, compared with hyperbaric oxygen or the membrane technique alone. Synergistic effects can thus be achieved by the use of membranes and stimulatory factors for bone regeneration. PMID- 8351491 TI - Comparison of quality of speech after Veau-Wardill-Kilner pushback operation and the Cronin modification in the primary treatment of cleft palate. AB - The quality of speech was compared in 124 young adults with isolated cleft palate. Forty-seven subjects were excluded because of the presence of factors that might have biased the evaluation of the success rate of the two operations studied, leaving 77 subjects who had undergone primary palatoplasty for analysis. One stage closure of the soft and hard palate was done for 43 patients by the mucoperiosteal palatal V to Y pushback technique (Veau-Wardill-Kilner, group V), and 34 underwent the Cronin modification (group C). Their speech was tape recorded, analysed by three qualified listeners, and hypernasality assessed by four published hypernasality indexes. More subjects in group C achieved normal resonance than in group V, who had higher hypernasality index scores than group C. The groups managed pressure consonants similarly. Only a few patients had weak plosives, audible nasal air emission, or compensatory articulation. Similar numbers of secondary operations were done for both groups. However, group V would have actually required secondary surgery more frequently than group C. PMID- 8351490 TI - The use of preformed HTR polymer implants for chin augmentation. A preliminary report. AB - Ten patients with microgenia had their chins augmented with HTR polymer implants. The implants were inserted intraorally and fixed rigidly with a titanium screw. The postoperative course was uneventful except in one patient who had wound dehiscence and was resutured. This patient and all the others were clinically and radiographically stable at one year follow up. PMID- 8351492 TI - Facial growth after pharyngeal flap surgery in cleft palate patients: a five-year longitudinal study. AB - To assess the influence of a pharyngeal flap on facial morphology in patients with cleft lip and palate, we studied prospectively 20 consecutive patients with cleft lip and palate aged 4 to 9 years who needed a pharyngeal flap. We also studied a control group of 20 subjects matched with regard to age, sex, diagnosis, and method of primary treatment. Facial growth was followed for five years, beginning one year before operation. Before operation there was no significant difference between the operated group and the reference group as far as skeletal facial dimensions and angular measurements were concerned. The longitudinal comparison within each group showed that there was a change in mandibular growth direction backwards and downwards in the operated group. The changes in facial growth after pharyngeal flap operation were similar to those reported in patients with enlarged adenoids. Four years after operation, the change in the direction of mandibular growth did not result in any specific facial form that could be identified clinically. PMID- 8351493 TI - Latissimus dorsi breast reconstruction. Long term results and return of sensibility. AB - The long-term results of 44 patients who underwent breast reconstruction after mastectomy with latissimus dorsi musculocutaneous flaps with endoprostheses were studied. Good symmetry without a brassiere was achieved in 15 patients, slight asymmetry in 24 and poor symmetry in five (11%). Symmetry when a brassiere was worn was acceptable in all but one of the patients (43/44). A third of the patients (n = 13) had developed unacceptable (grade III or IV) capsular contraction, but 39 (89%) of the patients studied were satisfied with the long term reconstruction. Cutaneous sensibility, measured by von Frey's test, had returned to 28 (64%) of the cutaneous skin islands, to their medial parts in particular. The flaps in patients who had received concentrated radiation or who had large prostheses remained numb. Sensation was normal in the scars of the donor areas in all but three patients. Latissimus dorsi breast reconstruction with an endoprosthesis is safe and simple. It gives a subjectively satisfactory result in nine out of 10 patients and is therefore a valuable method of reconstruction after mastectomy. PMID- 8351494 TI - Reconstruction of ischial pressure ulcers by skin expansion. AB - Ten patients, eight of whom were paraplegic, have had ischial pressure ulcers treated by skin expansion. Skin expanders 680 ml in size were inserted subcutaneously on the posterior aspect of the thigh. They were filled during a short period without complications, the filling being monitored with a cutaneous tonometer. At a second operation the ulcers were repaired easily with the expanded flaps. After a few weeks the patients were able to undergo a programme of rehabilitation that included sitting with the expanded flaps. No ulcers recurred during a median follow-up of 12 months (range 8-34). PMID- 8351496 TI - Dermatome shaving of psoriasis. Seven years experience in 112 patients. AB - Data from the records of 112 patients who were treated by dermatome shaving for psoriasis vulgaris were analysed. A psoriatic "area" was defined as all psoriatic skin lesions present in a specific region at the first treatment, and 108 patients with 202 areas were included in the study. In 68 patients the treatment was limited to a single area, and 40 patients had from two to nine areas treated, mainly on the legs and arms. Complications occurred in nine patients; one had a wound infection that required treatment with an antibiotic, in five patients healing was prolonged, and three patients developed unsightly scars. Thirty-seven patients and 104 areas have not recurred during mean follow-up periods of 1.4 years and 1.9 years, respectively. In all 108 patients the median recurrence free period was eight months (range: 0-5.6 years). The median recurrence free period for the 202 areas was 13 months (range: 0-8.2 years). Reshaving of partial recurrences in 46 patients led to 40% that did not recur. The best prognostic factor available is to do a test shave before initiating more extensive treatment. PMID- 8351495 TI - Skin expansion. Long term follow up of complications and costs of care. AB - To find out our rate of complications after tissue expansion, and the cost of treatment in terms of use of hospital resources and length of sick leave, we analysed our experience of 181 expansion treatments in 97 patients undertaken between 1986 and 1991. There were 60 women and 37 men, with a mean age of 22 (range 1-74). Twenty patients had more than one period of treatment (range 2-8). The most common conditions treated were naevi (n = 75); scars (trauma--n = 33, burns--n = 17, and operations--n = 16); and breasts that required reconstruction (n = 15). Of the 181 expansions there were 29 failures (16%), and 117 complete successes (64%); fifteen of the latter developed minor complications (8%), 35 were partly successful (20%). There were 77 complications in 71 treatments (38%), and 45 expanders (25%) had to be removed prematurely because of complications. The most common complications were skin penetration (n = 15), minor infection (n = 13), and breakdown of the surgical wound (n = 13). The median (range) inpatient hospital stay was 8 days (2-39); number of visits to the outpatient clinic for filling 7 days (0-20); and total treatment time/patient 82 (19-286). We conclude that skin expansion is a useful technique, but that there is room for improvement in reducing the rate of complications and the amount of time that patients spend being treated. PMID- 8351497 TI - Tissue expansion for the treatment of myelomeningocele. Case report. AB - A baby boy who had been born with a large myelomeningocele had a ventriculoperitoneal shunt inserted at the age of 6 months. Two months later it was revised, after which he developed satisfactorily both mentally and physically. He presented at the age of 13 months because the epithelialisation of the myelomeningocele was both fragile and incomplete. Enough soft tissue was obtained to cover the defect, which was 13 x 10 cm, by the use of two 600 ml expanders placed subcutaneously one on either side of the deformity. PMID- 8351498 TI - Microsurgical two-stage reconstruction of the thumb. Case report. AB - A 40-year-old patient presented with traumatic amputation of the thumb and index finger. The second metacarpal bone fragment was transposed to lengthen the first metacarpal bone. A free flap from the lateral forearm was used to reconstruct the thenar region. Later, the second free toe-to-hand transfer was done from which he made a good recovery, achieving active flexion and extension in all joints. PMID- 8351499 TI - Fracture of the scaphoid associated with volar displacement of a lower radial epiphyseal fracture. Case report. AB - A 13-year-old boy fell off his bicycle and landed on his outstretched left hand, sustaining a Salter-Harris type II fracture of the lower radial epiphysis with volar displacement, and an undisplaced fracture across the waist of the left scaphoid. After manipulation, and immobilisation for six weeks, he made a complete recovery and has no residual deformity. We hypothesise that the fracture was caused by the weight of the body being taken by the relatively stiff and immobile hand, and could find no report of a similar case. PMID- 8351500 TI - Acute carpal tunnel syndrome caused by peritendinitis calcarea. Case report. AB - Two women presented with similar symptoms of acute pain in the hand that was diagnosed as acute carpal tunnel syndrome caused by peritendinitis calcarea. Radiological examinations in both cases showed calcifications in the carpal tunnel. Both patients were operated on immediately and the median nerve was decompressed. Both were completely relieved of pain after operation and hand function returned to normal. PMID- 8351501 TI - Interpreting laser Doppler recordings from free flaps. AB - Although the transfer of free flaps is nowadays accomplished with an increasing degree of safety, thrombosis of the microvascular anastomoses is still a problem. In order to avoid delay in re-operating, various methods for objective blood flow monitoring have been tried, among them Laser Doppler Flowmetry (LDF). When one reviews the literature, it is apparent that opinions differ about whether or not LDF is a reliable technique for this purpose. To focus on the need to interpret continuous recordings, this paper reports our findings in six latissimus dorsi free flaps chosen from our series of LDF monitoring procedures. One uneventful flap, no. 1, had an immediate postoperative LDF value of 4.5 perfusion units (PU). LDF values improved during the recovery period and the graphic recording showed fluctuations due to normal physiological variations of the blood flow in the flap. Another uneventful flap, no. 4, showed the same pattern, though at an appreciably lower level, 2 PU, on average. Flap no. 2 had an acceptably high value of 3.5 PU despite suffering a venous thrombosis. However, the LDF recording showed no fluctuations and the value declined gradually. Another flap, no. 3, showed fluctuations and blood flow was normal although the value decreased to 2.5 PU. In flap no. 5, any value between 2 and 3.5 PU could be obtained merely by adjusting the position of the probe in the holder. In no. 6, the LDF value suddenly dropped, accompanied by a decrease in the total amount of backscattered light, indicating venous obstruction which was confirmed at re operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351502 TI - Rate of recovery after flexor tendon repair in zone II. A prospective longitudinal study of 145 digits. AB - A series of 145 digits were treated with three controlled motion programmes after flexor tendon repair in zone II. Active interphalangeal joint motion was measured four, six and 12 weeks; six months and one year after operation. Although there were differences in the final results among the groups, the rate of recovery from the end of the controlled motion period (four weeks after operation), was not significantly different in the three treatment groups. Overall, a mean of 37% of the final distal interphalangeal joint range of motion and 9% of the final proximal interphalangeal joint range of motion was recovered between three months and one year postoperatively. In only 10 of 27 digits with a poor result (combined interphalangeal joint range of motion less than 90 degrees) at three months, was the result still poor at one year; 10 regained another 40 degrees or more, and eight another 50 degrees or more. The results indicate that it is worth waiting six or 12 months before considering tenolysis. PMID- 8351503 TI - Neurophysiological diagnosis of the carpal tunnel syndrome: evaluation of neurographic techniques. AB - Twenty-eight patients with a clinical diagnosis of carpal tunnel syndrome underwent extensive neurographic examination. The results were compared with those in 86 normal subjects who had no signs or symptoms. The widely used methods of measuring distal motor latency from wrist to thenar and the sensory conduction velocity from the first and third fingers to the wrist gave highly significant differences between the carpal tunnel syndrome group and the control subjects. There was, however, a large overlap of values between the two groups and the discriminative power of the tests was not sufficient to make a diagnosis. Both methods for selectively determining the conduction velocity across the carpal tunnel distinguished clearly between hands with carpal tunnel syndrome and the control group, with no overlap of values. The results support the diagnostic validity of a fractionated study of conduction velocity across the carpal tunnel with surface electrodes, a test that can easily be done by a trained nurse or EMG technician under the supervision of a clinical neurophysiologist. PMID- 8351504 TI - Image freezing or progressive thawing? PMID- 8351505 TI - Long-range planning initiative for AASCIN: a Delphi study. PMID- 8351506 TI - The prevention and management of urinary tract infections among people with spinal cord injuries. National Institute on Disability and Rehabilitation Research consensus statement. January 27-29, 1992. AB - The Urinary Tract Infection Consensus Conference brought together researchers, clinicians, and consumers to arrive at consensus on the best practices for preventing and treating urinary tract infections in people with spinal cord injuries; the risk factor and diagnostic studies that should be done; indications for antibiotic use; appropriate follow-up management; and needed future research. Urinary tract infection (UTI) was defined as bacteriuria (102 bacteria/ml of urine) with tissue invasion and resultant tissue response with signs and/or symptoms. Asymptomatic bacteriuria represents colonization of the urinary tract without symptoms or signs. Risk factors include: over-distention of bladder, vesicoureteral reflux, high pressure voiding, large post-void residuals, presence of stones in urinary tract, and outlet obstruction. Possible physiologic/structural, behavioral, and demographic risk factors were identified also, Indwelling catheterization, including suprapubic, and urinary diversion and the drainage methods most likely to lead to persistent bacteriuria. Infection risk is reduced with intermittent catheterization, but more severely disabled people who require catheterization by others are at greater risk for UTIs. Clean self-intermittent catheterization does not pose a greater risk of infection than sterile self-intermittent catheterization and is much more economic. However, care must be given to proper cleansing of reusable catheters. Quantitative urine culture criteria for the diagnosis of bacteriuria include: catheter specimens from individuals on intermittent catheterization > or = 10(2) cfu/ml; clean-void specimens from catheter-free males using condom collection devices > or = 10(4) cfu/ml; and specimens from indwelling catheters of any detectable concentration. Dip stick screening tests may offer promise as an early warning system of UTI since they can be self-administered. Symptomatic UTI should be treated with antibiotics for 7 to 14 days. Longer courses have not been beneficial. In patients with symptomatic UTIs, it is not necessary to wait for the results of cultures before starting treatment. Asymptomatic bacteriuria need not be treated with antibiotics. There is little evidence presently to support the use of antibiotics to prevent infections. Following a recent episode of febrile UTI, possible contributing prior events should be reviewed. The upper tracts should be evaluated (imaging studies) to identify possible abnormalities. A common concern among people with spinal cord injuries is that physicians will alter bladder management programs without regard to lifestyle needs. Social/vocational flexibility may be more important to them than a state-of-the-art bladder management program. Future research should focus on obtaining more representative samples and investigate psycho-social-vocational implications as well as additional clinical-medical factors. PMID- 8351508 TI - Bringing research to the bedside through nursing process. PMID- 8351507 TI - Descriptive study of bowel care practices and equipment in spinal cord injury. AB - 46% of the 277 SCI veterans responding to the survey used bowel care/shower chairs at home. Of those who regularly used these chairs (N = 147), over 66% felt their safety was compromised by their use. Caregivers reported similar dissatisfaction with existing bowel care/shower chairs. Primary concerns related to difficulty in assisting with safe transfers were, lack of hand access to perianal area for digital stimulation, lack of ease in rolling and turning the chair, difficulty in keeping the chair clean, and lack of durability of chair, particularly with brakes and seat. Primary safety risks included patient falls and pressure ulcer development. Reports of chair related patient falls (35%) and pressure ulcers (24%) were common in the SCI patients surveyed. Less than 54% were satisfied with the design and usability of bowel care/shower chairs. PMID- 8351509 TI - What are some factors that influence incorporation of urinary management routines into a person's daily schedule? PMID- 8351510 TI - Who is normal? PMID- 8351511 TI - Off to an early start. PMID- 8351512 TI - T cell anergy. PMID- 8351513 TI - Diet and primate evolution. PMID- 8351514 TI - The great radium scandal. PMID- 8351515 TI - Antisense oligonucleotides as therapeutic agents--is the bullet really magical? AB - Because of the specificity of Watson-Crick base pairing, attempts are now being made to use oligodeoxynucleotides (oligos) in the therapy of human disease. However, for a successful outcome, the oligo must meet at least six criteria: (i) the oligos can be synthesized easily and in bulk; (ii) the oligos must be stable in vivo; (iii) the oligos must be able to enter the target cell; (iv) the oligos must be retained by the target cell; (v) the oligos must be able to interact with their cellular targets; and (vi) the oligos should not interact in a non-sequence specific manner with other macromolecules. Phosphorothioate oligos are examples of oligos that are being considered for clinical therapeutic trials and meet some, but not all, of these criteria. The potential use of phosphorothioate oligos as inhibitors of viral replication is highlighted. PMID- 8351516 TI - Group II intron RNA catalysis of progressive nucleotide insertion: a model for RNA editing. AB - The self-splicing bl1 intron lariat from mitochondria of Saccharomyces cerevisiae catalyzed the insertion of nucleotidyl monomers derived from the 3' end of a donor RNA into an acceptor RNA in a 3' to 5' direction in vitro. In this catalyzed reaction, the site specificity provided by intermolecular base pair interactions, the formation of chimeric intermediates, the polarity of the nucleotidyl insertion, and its reversibility all resemble such properties in previously proposed models of RNA editing in kinetoplastid mitochondria. These results suggest that RNA editing occurs by way of a concerted, two-step transesterification mechanism and that RNA splicing and RNA editing might be prebiotically related mechanisms; possibly, both evolved from a primordial demand for self-replication. PMID- 8351517 TI - Inhibition of an in vivo antigen-specific IgE response by antibodies to CD23. AB - Immunoglobulin E (IgE) mediates many allergic responses. CD23 is a 45-kilodalton type II transmembrane glycoprotein expressed in many cell types. It is a low affinity IgE receptor and interacts specifically with CD21, thereby modulating IgE production by B lymphocytes in vitro. In an in vivo model of an allergen specific IgE response, administration of a rabbit polyclonal antibody to recombinant human truncated CD23 resulted in up to 90 percent inhibition of ovalbumin-specific IgE synthesis. Both Fabs and intact IgG inhibited IgE production in vitro and in vivo. Thus, CD23 participates in the regulation of IgE synthesis in vivo and so could be important in allergic disease. PMID- 8351518 TI - Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. AB - The pericentric inversion of chromosome 16 [inv(16)(p13q22)] is a characteristic karyotypic abnormality associated with acute myeloid leukemia, most commonly of the M4Eo subtype. The 16p and 16q breakpoints were pinpointed by yeast artificial chromosome and cosmid cloning, and the two genes involved in this inversion were identified. On 16q the inversion occurred near the end of the coding region for CBF beta, also known as PEBP2 beta, a subunit of a heterodimeric transcription factor regulating genes expressed in T cells; on 16p a smooth muscle myosin heavy chain (SMMHC) gene (MYH11) was interrupted. In six of six inv(16) patient samples tested, an in-frame fusion messenger RNA was demonstrated that connected the first 165 amino acids of CBF beta with the tail region of SMMHC. The repeated coiled coil of SMMHC may result in dimerization of the CBF beta fusion protein, which in turn would lead to alterations in transcriptional regulation and contribute to leukemic transformation. PMID- 8351519 TI - Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. AB - Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). Complete screening of the SOD1 coding region revealed that the mutation Ala4 to Val in exon 1 was the most frequent one; mutations were identified in exons 2, 4, and 5 but not in the active site region formed by exon 3. The 2.4 A crystal structure of human SOD, along with two other SOD structures, established that all 12 observed FALS mutant sites alter conserved interactions critical to the beta-barrel fold and dimer contact, rather than catalysis. Red cells from heterozygotes had less than 50 percent normal SOD activity, consistent with a structurally defective SOD dimer. Thus, defective SOD is linked to motor neuron death and carries implications for understanding and possible treatment of FALS. PMID- 8351521 TI - Basic research: the gray zone. PMID- 8351522 TI - Physicists take a hard look at vision. PMID- 8351520 TI - Dynamics of the hippocampal ensemble code for space. AB - Ensemble recordings of 73 to 148 rat hippocampal neurons were used to predict accurately the animals' movement through their environment, which confirms that the hippocampus transmits an ensemble code for location. In a novel space, the ensemble code was initially less robust but improved rapidly with exploration. During this period, the activity of many inhibitory cells was suppressed, which suggests that new spatial information creates conditions in the hippocampal circuitry that are conducive to the synaptic modification presumed to be involved in learning. Development of a new population code for a novel environment did not substantially alter the code for a familiar one, which suggests that the interference between the two spatial representations was very small. The parallel recording methods outlined here make possible the study of the dynamics of neuronal interactions during unique behavioral events. PMID- 8351523 TI - Role of gene defect in hereditary ALS clarified. PMID- 8351524 TI - Evolutionists take the long view on sex and violence. PMID- 8351525 TI - Thinking about brain cell assemblies. PMID- 8351527 TI - A good life. PMID- 8351526 TI - Death and dignity. PMID- 8351528 TI - State authority, medical dominance, and trends in the regulation of the health professions: the Ontario case. AB - The relationships amongst the health professions and between them and the state are rapidly changing. I argue that analysis of these relationships has to take into consideration: the fact that medicine played an intermediary role (through medical dominance in health care) between the state and the other health occupations; the permeability of the boundaries of the state and the professions; and the dual nature of professional organizations (as sites of intra-occupational conflict and as possible vehicles of extra-occupational control). In Ontario the medical profession partially 'mediated' the relationships between 'non-physician' health occupations and the state through medical control over other health care occupations. National/provincial health insurance brought the state into the health care system as an actor and forced a reconsideration of its relationships with medicine and with the other health care occupations. The state came to be directly involved in 'rationalizing' health care. This involvement meant curbing the power of medicine and modifying the relationships between medicine and the para-medical occupations. State influence is partly constructed through a particular kind of professional organization, namely, the professional College. These changing relationships are illustrated by historical and recent developments regarding medicine, nursing and chiropractic in Ontario. PMID- 8351529 TI - [Children for the aged. Sibling configuration and support for aged parents in the rural south-western area of France]. AB - The support of the dependent elderly is conditioned by the availability of the family, particularly of children, even when assistance services help the elderly stay at home. But it is difficult to tell if the elderly will have descendants capable of providing for them. A survey carried out in the rural South-Western area of France shows the importance of taking into account sibling configuration when seeking support for the old and disabled. The analyses presented here result from the joint utilization of an epidemiological study based on a questionnaire (N = 405) and a sociological survey on family history: 74 elderly people from the initial sample as well as several of their relatives and friends were interviewed at length on the conditions of support at home. Three main sibling configurations have been established: the only child, several children of the same gender, several children of different genders. They were related to three types of distances between parents and children: co-habitation, vicinity, remoteness. If one finds as many children co-habitating with at least one parent in one-child families as in the whole sample (33%), it means that family support mostly depends on the transfer of property for farmers and tradesmen: in this area, the heir must provide for his ageing parents. But there are marked differences according to the gender of the children: a boy is only likely to stay with his parents if he inherits their professional activity. On a qualitative level, the question dealt with in this article is the following: how can one plan for one's old age according to the rigidity of the number, the order and the gender of the children? PMID- 8351530 TI - The utility of health at different stages in life: a quantitative approach. AB - Thirty students and thirty-five elderly people compared the quality of life of imaginary patients of different ages suffering from end-stage renal disease. By manipulating the time the imaginary patients had to be on a transplantation waiting list, the utility of health at different periods of life could be compared. Except for the very young, respondents found health in the early periods of life to be twice as important as in the last decade of life. Health at age 35 had an utility somewhere between these two extremes. The responses of the elderly people showed remarkable resemblance to the students' responses, suggesting that the results reflect a general ethical standard. The values found were tested by means of a factorial design and found to fulfill the qualifications of an interval scale. PMID- 8351531 TI - A longitudinal study of the impact of behavioural change intervention on cleanliness, diarrhoeal morbidity and growth of children in rural Bangladesh. AB - A community-based intervention was developed through direct participation of the target population in assessment and iterative trials to improve hygiene practices and to reduce childhood diarrhoea in lowland rural Bangladesh. A total of 185 (98%) households with children ages 0-18 months in five contiguous villages were targeted for the interventions. A comparison site was selected for a detailed observational study and for use as a control for the intervention. About 97% of all households with children ages 0-18 months were enrolled for study at the control site. Children in this age group were targeted because at this developmental stage they were most vulnerable to diarrhoeal morbidity and malnutrition (related to unhygienic practices). The intervention was implemented with the assistance of village leaders through a "Clean Life" campaign by local project workers and volunteer mothers who were chosen from the target households. The intervention activities started in January 1986 and lasted for 7 months. Higher adoption rates of the intervention were associated with better cleanliness status, which was related to lower diarrhoea and malnutrition rates in the intervention site. The results of between-site longitudinal analyses showed that after the intervention, the intervention site had substantially higher cleanliness scores, lower diarrhoeal morbidity, and better growth status compared to those of the control site, with differences increasing over time. The findings suggest that this type of community-based intervention can be very beneficial in modifying hygiene behaviours and lowering childhood diarrhoea and malnutrition. PMID- 8351532 TI - Cost-effectiveness analysis of prenatal screening and vaccination against hepatitis B virus--the case of Belgium. AB - The study examines the cost-effectiveness of screening pregnant women in Belgium for the presence of hepatitis B virus (HBV) and of vaccinating the newborns if necessary. The alternative strategy considered is 'doing nothing'. The rate of carriership among a sample of pregnant women in Belgium amounts to 0.67%. If a pregnant woman is a carrier of the virus, there is an average probability of 30% that she will transmit the virus to her newborn. Later in life, this baby will be at risk from serious complications, such as chronic active hepatitis, cirrhosis and primary hepatocellular cancer. However, medical costs will be induced by screening and vaccination campaigns, lab-tests, vaccine costs, etc. On the other hand, resources will be saved by the prevention of severe complications of the disease. However, costs dominate savings, the incremental cost-effectiveness ratio for the screening and vaccination strategy amounting to 583,581 BEF per life-year saved. To check the stability of the cost-effectiveness ratio, a sensitivity analysis has been performed on some crucial parameters: the ratio is found to be sensitive to the prevalence of HBV among pregnant women, to the costs for screening and vaccination and to the discount rate. Increasing the treatment costs for a HBV complication hardly changes the cost-effectiveness ratio. PMID- 8351533 TI - Determinants of infant mortality in Malawi: a spatial perspective. AB - This paper examines the spatial variation of infant mortality in Malawi between 1977 and 1987. Data from the 1977 and 1987 censuses are used in simple correlation and forward stepwise regression analysis to explain and/or predict the variation and change of infant mortality is strongly associated with a number of demographic and socioeconomic variables. Region in which a district finds itself also matters as far as levels of infant mortality are concerned. With a rapidly expanding population, the study concludes that the reduction of infant mortality throughout the country should be vigorously pursued by the government of Malawi. Fertility will continue to be high if infant and childhood mortality persist at current levels. PMID- 8351534 TI - Determinants of pregnancy outcomes and targeting of maternal health services in Jamaica. AB - Detailed nationally representative population level data were used to investigate the pre-natal care and delivery experiences of pregnant women in Jamaica. The results of this study show that: (a) demographic criteria (particularly first births) and self-reported clinical pregnancy complications are valid predictors of deleterious maternal health outcomes and can be used to stratify mothers into risk groups. (b) There appears to be a significant problem of under and inappropriate utilization of pre-natal care services by all women and in particular by demographically 'high risk' women, i.e. young, first time mothers. Significant proportions of the latter group report either no pre-natal care visits at all or visits which are later than the first trimester. The problems of delayed initiation of pre-natal care are specially exacerbated for poor, teenage mothers who happen to be living in the Kingston Metropolitan Area. (c) In terms of the content and quality of pre-natal care services the message is somewhat mixed. On the positive side the pre-natal care system is doing a moderately satisfactory job with regard to diagnostic tests and educational advice. On the negative side however, the fact that once women enter the health care system they all receive the same moderately adequate care (in terms of diagnostic evaluations and educational advice) with no attempt to focus particular attention on high risk mothers is troublesome. (d) With regard to appropriate delivery venues for pregnant women, pre-natal care visits do not appear to significantly influence the choice of delivery venues. Moreover, rich urban women are much more likely to deliver in a hospital than their rural peers. In conclusion, the study discusses the social and behavioral context of these results, addresses the policy implications and makes some recommendations to improve maternal health services. PMID- 8351535 TI - Disease and mortality among gold miners of Ghana: colonial government and mining company attitudes and policies, 1900-1938. AB - This article traces the causes of high mortality rates among African gold miners in the former British colonial territories of the Gold Coast and Ashanti, 1900 1938. No previous studies exist for the early decades owing to the neglect by both mining companies and government officials to keep adequate statistics on African miner death rates, a flaw which reinforced the lackadaisical response of the government to problems of prevention and treatment. A milestone report issued in 1924, demonstrating that sanitary precautions, housing conditions and medical treatment for most African miners were wretched, forced the colonial state to gather regular data on Africans and make long overdue improvements, so that mortality rates for underground miners slowly declined by the time of the Second World War. But the published statistics concealed from view the far greater incidence of general deaths from pulmonary and respiratory tract disease among short-term migrant labourers, who lived in the mining towns, but returned to die in their home villages. PMID- 8351536 TI - Social determinants of child health in Yemen. AB - Much of child illness in developing countries can be explained by what have been called, 'proximate determinants,' principally infant feeding practices and preventive and curative care. During previous field research in a small village in Yemen the author observed that despite the uniformly unhealthy environment, a minority of the families carried most of the burden of child illness and death. This study was carried out to document that observation, and to suggest an explanation. The study used quantitative techniques to map child health in the community and identify a sub-sample for subsequent in-depth questioning and observation. What distinguished women with healthy and unhealthy children was the level of resources under their control and the way they managed them; their social support or lack of it; and their passive or active attitudes toward life. Detailed stories are presented for five of the women. Although biological explanations for ill health can lead to useful interventions, the social and economic problems of the 'multi-problem family'--well-recognized in industrialized countries--must also be addressed to improve child health. PMID- 8351537 TI - [Mbombo: therapeutic ritual for high-risk children in rural Zaire]. AB - The mbombo is a popular ritual practice, with preventive and curative implications, of a rural society in central Africa. This rite is used by: pregnant women who have lost several children by abortion, at childbirth, or during their first year of life; by women who get pregnant after a long spell of primary or secondary infertility; by their children until they can walk; and by twins and their mother. The principal characteristics of the rite include: the separation of mother and child from their family, a long period of marginality under the continuous protection of a ritualistic healer, and a progressive reinsertion in the therapeutic support group, composed of the family and the community of sufferers. When one analyses the meanings and operational functions of the global ritual process of this therapy, which incidentally takes into account several midwifery techniques, it is not only a fecundity ritual, but also a rite of initiation, protection, purification and passage. Thus it is a global therapy involving besides child survival, the restoration of a new physiological, psychological, religious and social identity of the ritual subjects. PMID- 8351539 TI - Vasectomy as a reason for donor insemination. AB - Among 200 couples referred for counselling with a view to donor insemination (DI) were 21 whose request arose from an earlier vasectomy. This had been judged irreversible, apart from one case where the man had been sterilised for genetic reasons and therefore had not sought reversal. An overall incidence of 10.5% indicates that vasectomy may lead to fertility problems in the event of remarriage, which has become more common with an increasing divorce rate. All 21 husbands but only 3 wives had been previously married; 3 former wives had died, otherwise all previous marriages had ended in divorce. Most husbands were considerably older than their second wives, especially as compared with the majority of men in the larger series who were still in a first marriage. Their relative maturity may have helped them to respond more sensitively to their wives' maternal needs when they already had children of their own. During a follow-up interval of up to 8 years, 2 couples had separated after a brief relationship but 9 of the other 12 contacted had become parents by DI. The 3 remaining couples included a wife who at the latest report was 5 months pregnant, and 2 who were still pursuing treatment. Despite the low failure rate in this small series we should bear in mind that DI is not an ideal solution to the problem of male infertility, nor always even acceptable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351538 TI - An application of Ajzen's theory of planned behaviour to predict mothers' intention to use oral rehydration therapy in a rural area of Benin. AB - The aim of this study was to identify the psychological factors influencing mothers' intentions to use oral rehydration therapy (ORT) for the treatment of children's diarrhea in rural areas in South Benin. The subjects were 128 illiterate and animist mothers, selected at random in the areas of Pahou and Avlekete. Mothers were interviewed at home, using a pre-tested instrument investigating predictors of motivation as defined in Ajzen's theory of planned behaviour. The variables measured were intentions, attitudes, subjective social norm, perceived behavioural control and socio-demographic indicators. The regression of intention on all variables yielded an adjusted R2 of 0.40 (P < 0.0001), with perceived consequences of using ORT, perceived barriers to its use, and the zone of habitation being the significant predictors. The results suggest that the promotion of the use of ORT for treatment of diarrhea, in these areas, should be facilitated if the mothers perception of the advantages of using ORT is reinforced and if they have easier access to the health care services offered by local village health workers. PMID- 8351540 TI - The relationship between parenting stress and social support in mothers of children with learning disabilities: a Chinese experience. AB - This study examined the relationship between parenting stress and social support in a random sample of 100 mothers with children at a school for children with learning disabilities, and a control group of 75 mothers with similarly aged non handicapped children. Mothers of children at Zhi Ling school were found to have significantly more stress and significantly less support than those in the control group. Parenting stress in the control group was also found to be relatively high when compared with what are considered to be normal levels in the West. No significant correlation was found between total parenting stress and social support. It is suggested that further studies need to differentiate between satisfaction with support that is actually received and the perceived quality of available support. PMID- 8351542 TI - Prevention of bicycle-related injuries in childhood: role of the caregiver. AB - To assess perceptions of bicycle-related head injuries, helmet use, and safety practices, we had questionnaires distributed to caregivers of 2,500 children in the third through sixth grades; 1,006 (40.2%) completed surveys were returned. Eight hundred thirty-two caregivers (82.7%) indicated that they had a child cyclist in their household; approximately 65% responded that they believed head injury was likely if their child was involved in a bicycle mishap. A majority (approximately 70%) also said that a bicycle helmet may prevent head injury in between 25% and 75% of all occurrences. Yet 758 (91.1%) students did not own or have access to a bicycle helmet. Among the caregivers whose child did not have a bicycle helmet, 530 (69.9%) stated that they had never thought about purchasing one. Caregivers of both helmeted and nonhelmeted youngsters indicated concern for bicycle safety (100% versus 94%, respectively). Most caregivers (approximately 64%) stated that they would encourage their child to attend a bicycle safety camp. These findings suggest that caregivers perceive the dangers associated with bicycling but are not cognizant of available programs and methods that prevent the risk of serious injury to bicyclists. PMID- 8351541 TI - Use of tympanic thermometers to screen for fever in patients in a pediatric emergency department. AB - The use of tympanic thermometers has markedly increased over the past few years. While some authors have shown high correlation between rectal and tympanic readings, others have found low correlation. After noticing a failure of the tympanic thermometer to detect fever in obviously febrile pediatric patients, we prospectively evaluated its use in our emergency department. All patients less than 6 years of age who were brought in for care over a 2-week period were eligible for entry into the study. Nurses were trained in the proper use of the instruments before the study began. We used a calibrated tympanic thermometer (First Temp 2000A) and an electronic thermometer (IVAC 2080A). In all children the tympanic temperature was measured first, immediately followed by measurement of the rectal temperature. The 39 children entered into the study ranged in age from 2 to 71 months (mean of 27 months). Rectal temperature ranged from 97.8 degrees to 105.2 degrees F. The correlation between rectal and tympanic was low (r = .830) and was worse in patients with fever (r = .612). The mean difference was 0.8 degrees F, but was as high as 3.4 degrees F. The tympanic thermometer failed to identify five of the 15 febrile patients (T > or = 100.5 degrees F) in our study. We therefore conclude that the tympanic thermometer is not sensitive enough to be used to screen for fever in pediatric patients. PMID- 8351543 TI - Effect of anabolic steroids on HIV-related wasting myopathy. AB - Human immunodeficiency virus type 1 (HIV-1) is frequently associated with weakness and muscle wasting, referred to as HIV-1 wasting myopathy. This illness, often observed in the advanced stages of acquired immunodeficiency syndrome (AIDS), responds poorly to therapeutic intervention. We describe the cases of three AIDS patients with HIV-1 wasting myopathy who had a favorable response to anabolic steroids as evidenced by an improvement in strength, muscle bulk, body weight, and sense of well-being. PMID- 8351544 TI - Diagnosis of myocardial contusion. AB - From July 1988 to July 1990, 159 consecutive cases of major blunt chest injury were evaluated prospectively for myocardial contusion with serial electrocardiographic monitoring, cardiac isoenzyme studies, and two-dimensional echocardiography. One hundred and forty-seven cases in the series were assessable; 97 of the patients were male, and 50 were female. They ranged in age from 2 to 97 years (average, 38.5 years). There were five deaths, none of cardiac origin. Total lactate dehydrogenase (LDH) values were elevated in 115 patients (78%); total creatine phosphokinase (CPK) values were elevated in 100 (68%). Cardiac isoenzyme patterns were consistent with myocardial contusion in 18 patients (12%). Seventy-five patients had abnormal electrocardiograms, and 10 of these had ectopic rhythms. Two-dimensional echocardiograms were completed in 58 cases; 12 of these (21%) were abnormal. Nineteen patients (25%) with abnormal rhythms had elevated LDH values, and 26 (35%) had elevated CPK values. One patient (10%) with ectopy had an abnormal echocardiogram. Two patients (11%) with abnormal isoenzyme patterns experienced dysrhythmias. Costs for hospitalization and studies amounted to $1,886 per patient. Given the poor predictive value of laboratory testing in patients with significant (ie, symptomatic) cardiac contusion, observation alone with electrocardiographic monitoring and treatment of symptomatic dysrhythmias is an adequate and cost-conscious treatment. PMID- 8351545 TI - MacFee incision: a safe approach to the neck. AB - We reviewed 37 neck dissections done via the MacFee or double horizontal cervical incision to excise neoplasms located in the oral cavity and oropharynx, with draining cervical lymph nodes. One half of the patients had immediate reconstruction with myocutaneous flaps. Approximately 70% of the patients had advanced tumors and many were malnourished at presentation. Three wound complications involving the MacFee incision occurred in patients who were malnourished and required reconstruction. These wound complications were corrected with conservative therapy. Preoperative radiotherapy was a morbid cofactor. None of the patients had carotid artery involvement, wound dehiscence, or deep cervical infections. The MacFee incision can be used in major head and neck resections, with operative morbidity comparable to that of other techniques. PMID- 8351547 TI - Retroperitoneal tumors with vena caval extension: a multidisciplinary approach. AB - In cases of retroperitoneal tumor with extension to the inferior vena cava (IVC), complete resection improves survival, but may require cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA). Since 1985, eight patients at our institution have had complete resection of retroperitoneal tumors with IVC or right atrial involvement. Preoperative evaluation included intravenous pyelography, computed tomography of the chest and abdomen, renal arteriography, and venography or magnetic resonance imaging of the IVC. Operative technique was determined primarily by the extent of IVC or RA involvement and included combined median sternotomy and laparotomy, control of the intrapericardial IVC, and radical tumor resection. IVC tumor thrombectomy was done using either temporary vascular occlusion, CPB, or CPB with HCA. Complete resection for improved survival of retroperitoneal tumors with IVC extension is technically feasible with acceptable morbidity and mortality rates. A multidisciplinary approach allows optimal management of these extensive tumors. PMID- 8351546 TI - Use of lumbar run-up technique for cervical myelography. AB - Cervical myelography by lumbar run-up produces excellent radiologic studies in most cases. Use of this technique avoids the hazards and pitfalls associated with a lateral cervical puncture. We discuss 92 cases, with excellent or good results in 98% and nondiagnostic studies in only 2%. Both of the poor technical studies were followed by computed tomographic myelography to produce diagnostic examinations in all cases. There were no serious complications. PMID- 8351548 TI - Giant lipomas of the hand and forearm. AB - Giant lipomas of the upper extremity are infrequently reported. They can alter function by restricting motion or producing compressive neuropathies. This report of four cases of giant lipoma in the hand and forearm illustrates these functional losses. The role of MRI and CT in preoperative evaluation of these lesions is discussed and a report of an anterior interosseous syndrome caused by a giant lipoma is presented. PMID- 8351549 TI - Safety and efficacy of teicoplanin for bone and joint infections: results of a community-based trial. AB - To evaluate the efficacy and safety of teicoplanin in the treatment of gram positive bone and joint infections, parenteral teicoplanin was used once daily in an average dose of 10.1 mg/kg (range 6 to 12 mg/kg) after loading to treat patients with acute or chronic osteomyelitis and septic arthritis. From the 66 patients who met criteria for initial enrollment, 60 gram-positive isolates were recovered from bone and joint fluid, and each was sensitive to teicoplanin at < or = 2 micrograms/mL (median 0.25 microgram/mL). Teicoplanin was more active in vitro against these isolates than either vancomycin or oxacillin. Among the 43 patients in whom microbiologic efficacy could be assessed, the initial pathogen was eradicated in 37 (86%). Clinically, 45 patients infected with staphylococci (including oxacillin-susceptible and oxacillin-resistant Staphylococcus aureus and coagulase-negative staphylococci) met predetermined criteria for completed adequate therapy. Of these, 39 (87%) responded favorably and became free of all signs of infection; 6 (13%) failed to respond or suffered relapse. Overall, 36 patients completed teicoplanin therapy at home. Adverse reactions necessitated discontinuance of therapy in 12 patients and included fever, rash, hepatic function test abnormalities, and renal insufficiency. We found teicoplanin to be effective and generally well tolerated for treatment of bone and joint infections by gram-positive organisms in a community setting. PMID- 8351550 TI - Surgical clipping of difficult intracranial aneurysms using deep hypothermia and total circulatory arrest. AB - Intracranial aneurysms often present a challenging problem for the neurosurgeon. A variety of techniques have been developed to deal with these lesions. Several subspecialists are frequently involved in such treatment. We present our experience in a community hospital using a previously described technique of hypothermic cardiac arrest and barbiturate cerebral protection. PMID- 8351551 TI - Continuing evolution of regionalized perinatal care: community hospital neonatal convalescent care. AB - We describe the convalescent care of 169 back-transported (to community hospitals) and 285 eligible but not back-transported very low birth weight (VLBW) infants. Eligible infants who were not back transported to a level I or II community hospital were transferred to a level II nursery within the Medical University of South Carolina (MUSC) for convalescent care. Study infants were admitted to the neonatal intensive care unit (NICU) at MUSC from July 1985 through June 1989. They were admitted after maternal transport to MUSC for imminent delivery (N = 159), out-born community delivery (N = 55), or in-born MUSC delivery (N = 240). The mean +/- SD birth weight and gestational age and the NICU admission diagnoses for the back-transported and non-back-transported neonates were similar. The mean +/- SD weight of neonates at the time they were back transported was significantly greater than the weight of neonates at the time of intrahospital transfer. In contrast, the discharge weight to home and total days hospitalized were significantly less in the back-transported infants. Five back-transported neonates (3%) and 12 non-back-transported neonates (4%) were readmitted to the NICU. The back-transported infants used more than 3,800 bed days at community hospitals that would otherwise have been spent in the regional center, thus facilitating increased parental and primary physician involvement in their care. PMID- 8351552 TI - Necrotizing infections of the perineum. AB - During a 6-year period, 10 patients were treated for severe necrotizing infections of the perineum (Fournier's gangrene) at the Edward Hines Veterans Administration Hospital (Hines, Ill). All were male, and their average age was 60 years. When known, duration of symptoms was 2 to 5 days. Prodromal signs such as edema, erythema, and pain frequently developed into rapidly spreading, full thickness cutaneous gangrene in less than 24 hours. All patients had significant concomitant disease; 60% were diabetic. All patients had expedient and aggressive initial debridement, usually within 24 hours of presentation to the surgical service. Each patient had a "second-look" debridement within 1 or 2 days. Debridement was done an average of 2.6 times per patient. The cause of the infection was noted in seven patients--five with perirectal abscess and two with urethral trauma. Suprapubic catheters were placed in both patients with urethral trauma. Diverting colostomy was done on two patients who had perirectal abscess as a nidus; eight patients were treated without colostomy. Polymicrobial bacteriologic flora were found in all patients, with a predominance of Escherichia coli, Bacteroides sp, and staphylococci. Broad spectrum antibiotics and early nutritional supplementation were given. Hospital stay averaged 4 weeks (range, 3 to 12 weeks). One patient died (mortality of 10%). Successful management of these patients requires expedient diagnosis, aggressive nutritional supplementation, and early and repeated debridement as clinically indicated. We have not found diverting colostomy to be a necessary part of the management of these patients even when the nidus is perirectal. PMID- 8351553 TI - Smokeless tobacco use in an outpatient veteran population. AB - Smokeless tobacco use is a significant health risk for carcinoma of the oropharynx, and has a high prevalence in the southern United States. To evaluate the potential demand for a smokeless tobacco cessation program, we surveyed patients attending the General Medicine Clinic of a Veterans Affairs Medical Center. The prevalence of smokeless tobacco use was 5.8%, which did not justify creation of a clinic-based cessation program. Since we observed adults using smokeless tobacco as a means to reduce or stop their smoking, smoking cessation programs should include counseling against smokeless tobacco use. PMID- 8351554 TI - Limited availability of medications for cancer patients. AB - We surveyed both chain and independent pharmacies within 10 counties of central South Carolina to determine the availability of certain medications that are often prescribed for patients during cancer treatment. One hundred twenty (59%) of the 202 surveys distributed were returned. Results indicate that many of the 65 products included in the survey are not stocked on a regular basis by the majority of the pharmacies that responded. Limited availability of these medications not only may prevent a patient from receiving timely drug therapy, but may exacerbate the anxieties and frustrations experienced by patients as they deal with their disease as well. This limited accessibility to medications could directly influence patient compliance. Therefore, patients need to be informed that availability is often limited, and that prescribed medications may require special ordering by their pharmacist. Awareness of this potential problem and increased communication among physicians, nurses, pharmacists, and patients could alleviate delays in drug therapy and improve the continuity of patient care. PMID- 8351555 TI - Oxyphil cell neoplasms of the thyroid gland. AB - Despite several extensive reviews of the literature within the past decade, the treatment of oxyphil cell tumors of the thyroid gland remains controversial. The foremost questions today concern the acceptable criteria for diagnosis of oxyphil malignancies and the appropriate surgical treatment of these neoplasms. This review provides a forum for debate on the treatment of oxyphil neoplasms, with emphasis on their unique histopathologic features and unpredictable clinical behavior. PMID- 8351557 TI - How safe are silicone breast implants? AB - The Food and Drug Administration's recent decision to limit the use of silicone gel breast implants was surrounded by a great deal of misleading information in the popular press. This article outlines the most relevant information available in the literature on the most often raised safety issues, including the carcinogenicity of silicone, speculation on a possible connection between silicone and autoimmune disease, the significance of gel bleed, and the effect of implants on mammography. In this attempt to better educate primary care physicians, we explain what is known about silicone gel breast implants so physicians can more wisely counsel their patients, who may be needlessly frightened by inaccuracies they have heard. PMID- 8351556 TI - Anorectal manometry: techniques and clinical applications. AB - Anorectal manometry has gained wide acceptance as a helpful method to objectively assess the apparatus of defecation provided by the anorectal sphincter. The standard manometric evaluation enables measurement of resting and squeeze pressures, as well as of the length of the functional anal canal (high pressure zone [HPZ]). More detailed assessment of radial and longitudinal pressure profiles can also be generated from vector volume and vector symmetry index assessment. Adjuvant techniques using an intrarectal balloon allow assessment of the rectoanal inhibitory reflex (RAIR), rectal sensitivity, capacity, and compliance. Although anorectal manometry can be used as a diagnostic test in diseases such as Hirschsprung's disease, more often it is used to assess common disorders such as chronic idiopathic constipation and fecal incontinence. Anorectal manometry has also been considered as a preoperative evaluation in patients having abdominal and anorectal procedures during which the state of continence can be jeopardized. PMID- 8351558 TI - Thomas Hodgkin (1798-1866): physician, Quaker, social activist, and pioneer English pathologist. PMID- 8351559 TI - Anaphylaxis due to latex. AB - The AIDS crisis has mandated the use of universal precautions and has "gloved" the health care environs--workers in hospitals, outpatient services, and basic city services, including emergency medical personnel, firemen, and police. Thus, in the future the number of reported serious latex reactions are expected to increase. Since most individuals at risk of sensitization might be identified by a simple symptom-related questionnaire, further latex exposure in that group could be limited. This could be accomplished by work area reassignment or using vinyl gloves if necessary. Autoinjectable epinephrine should be carried by those who have had anaphylaxis, and they should become proficient in its use. These measures could reduce the likelihood of serious latex-induced morbidity for health care workers, paramedical personnel, and patients. PMID- 8351561 TI - Concomitant abuse of clonidine and heroin. AB - We have reported the case of a 36-year-old woman who abused heroin and clonidine concomitantly. To our knowledge, this practice has never been reported in the medical literature, although it may be relatively common in certain communities. It may place the heroin abuser's health at additional risk and complicate therapy for overdose and withdrawal. PMID- 8351560 TI - Systemic lupus erythematosus-like illness associated with syndrome of abnormally large von Willebrand's factor multimers. PMID- 8351562 TI - Spinal epidural abscess due to Aspergillus sp in a patient with acquired immunodeficiency syndrome. PMID- 8351563 TI - Metastatic adenocarcinoma of the prostate: presentation as a pleural-based mass. AB - We have presented an unusual case of metastatic prostate carcinoma simulating a primary bone tumor. Although previous reports have described periosteal and "pseudosarcomatous" prostate metastases, no report makes reference to rib involvement. Furthermore, the large soft tissue component is highly unusual. This case illustrates that although such lesions are rare, in the older patient, metastases should be included along with primary tumors in the differential diagnosis of a spiculated bone lesion with prominent soft tissue involvement. PMID- 8351564 TI - Community-acquired Xanthomonas maltophilia pyelonephritis. AB - We have described the case of a patient with a community-acquired urinary tract infection with what is more typically a nosocomial pathogen. Our patient had not been hospitalized recently, and his only established risk factor for X maltophilia infection was chronic bladder catheterization. Although paraplegic and thus disabled, he was not debilitated. He had had no recent antibiotic therapy prior to the onset of symptoms, but he did have a history of multiple previous bladder catheter-related infections. We believe that chronic outpatient bladder catheterization, with its risk of recurrent infections, may provide another niche for emergence of this nosocomial pathogen. PMID- 8351565 TI - Torulopsis glabrata in the neonate: an emerging fungal pathogen. AB - Fungi are becoming increasingly common nosocomial pathogens in the neonatal intensive care patient. The fungus Torulopsis glabrata, a common skin inhabitant, is a potential pathogen in the high-risk neonate. In this report we have reviewed the cases of two infants in which systemic T glabrata infection was diagnosed. One patient survived without apparent sequelae; the other died before diagnosis and initiation of therapy. Five other cases of systemic infection by T glabrata in neonates have been reported previously, with only one survivor. Early recognition and treatment of this nearly uniformly fatal infection is imperative. PMID- 8351566 TI - Lithium-induced nephrogenic diabetes insipidus treated with indomethacin. AB - NDI occurs in 5% to 20% of patients receiving long-term lithium therapy. The associated polyuria usually resolves within 3 weeks of lithium discontinuance but can persist beyond a year. For such patients, hydrochlorothiazide and amiloride therapy has been hampered by the delayed effect and intrinsic side effects of these agents. We have described the case of a 66-year-old man with a history of bipolar disorder treated with lithium who was transferred to the intensive care unit with coma. Indomethacin therapy, at a dose of 50 mg every 8 hours, was begun and improvement of the NDI state was observed within 3 hours of lithium administration. There was complete normalization of mental status and laboratory studies after 36 hours. A complete 3-week course of indomethacin was required to keep the patient free of symptoms of NDI. We have also discussed the role of indomethacin in reversing lithium-induced NDI and reviewed pertinent prior reports in the literature. PMID- 8351567 TI - Combined coronary artery bypass and abdominal aortic aneurysmectomy: appropriate management in selected cases. AB - Patients with aortic aneurysms frequently have concomitant coronary artery disease, which carries the potential for significantly increased perioperative morbidity. Most cases of severe surgically correctable coronary artery disease can and should be treated by a separate operation before aneurysmectomy to lower operative cardiac morbidity and enhance long-term survival. Infrequently, a patient can have both unstable coronary disease and a large symptomatic aortic aneurysm. In this situation, a single procedure combining coronary artery bypass followed by aneurysmectomy, as illustrated by this case report, is a reasonable option and should be considered in the cases of carefully selected patients. PMID- 8351568 TI - Latex-induced anaphylaxis. PMID- 8351569 TI - Significant elevation of CA 19-9 in chronic active hepatitis. PMID- 8351570 TI - Splenectomy in the HIV-infected patient. PMID- 8351571 TI - [Common errors in small bowel examination--recognition, avoidance and quality assurance]. PMID- 8351572 TI - [Potential clinical applications of the FCR AC-1 in digital luminescence radiography]. PMID- 8351574 TI - [A comparison of magnetic resonance tomography and bone scintigraphy in the diagnosis of spinal bone metastases]. PMID- 8351573 TI - [Magnetic resonance tomographic studies in diseases of the hip joint]. PMID- 8351575 TI - [Principles and possibilities in the treatment of multiple injuries]. AB - The authors describe the therapeutic results in 135 patients with multiple injuries hospitalized at the Surgical Clinic of the Third Medical Faculty, Charles University in 1981-1990. The authors analyze the procedure in the treatment of these patients which is provided by the most experienced surgeon in collaboration with his assistant. A stage-by-stage procedure and early indication of operation is the most important aspect of treatment. PMID- 8351576 TI - [Anomalous origin of the right coronary artery from the pulmonary artery]. AB - The authors report a rare case of the abnormal origin of the right coronary artery from the pulmonary artery, presenting with severe angina. Surgical correction-reimplantation of anomalous origin into the aorta-was carried out. As demonstrated by angiography six months after operation, previously present collaterals to the right coronary artery are no longer visualized, right coronary is patent with filling from aorta. The patient is only mild symptomatic due to diffuse atherosclerotic stenosis of the left coronary artery. PMID- 8351577 TI - [Splenosis]. AB - Four patients where during childhood splenectomy was performed on account of a traumatic indication were after 9-12 years subjected to sonographic and scintigraphic examination focused on possible evidence of splenosis. In one case asymptomatic splenosis was detected by scintigraphy. PMID- 8351578 TI - [An unusual case of extensive false aneurysm of the superior gluteal artery]. AB - The authors describe an uncommon case of a false aneurysm of the superior gluteal artery, most probably of post-traumatic aetiology. The condition was resolved by exclusion of the aneurysm from the circulation. In the available literature no reference to a similar clinical finding and its treatment was found. PMID- 8351579 TI - [Endoscopic wedge-shaped lung biopsy--initial experience]. AB - The authors publish their initial experience with wedge-shaped pulmonary biopsy by the endoscopic route. The group is formed by 18 patients who were indicated for the operation on account of a disseminated pulmonary process in order to assess the micromorphological appearance of the affected lung tissue. Two patients developed a complication during operation which therefore was completed by minor thoracotomy. In who patients the authors observed after operation slow expansion of the pulmonary parenchyma. No death after the operation was recorded. The authors assume, based on their initial experience, that this operation will soon be included among common diagnostic operations and will help to facilitate the diagnosis and selection of treatment in patients with disseminated lung disease. PMID- 8351580 TI - [Use of the Apache II scoring system for clinical evaluation of the status of patients with gastrointestinal hemorrhage]. AB - The Apache II scoring system has been used to identify a clinical status of 10 patients, admitted to the intensive therapy unit with bleeding to gastrointestinal tract during the period 1. January - 30. Juni 1992. There were 9 men and 1 woman with mean age of 61.5 years (37-82). Apache II score was calculated before beginning of treatment and 4 times during following 3 days every 12 or 24 hours. The mean score before beginning of treatment was 9.7 (5 17). All the patients were treated exclusively by the conservative therapy with mean length of hospitalization 8, 1 days (4-12). The score during the therapy has had a decreasing tendency and statistically significant decrease came after 72 hours of treatment. Mortality rate at mentioned values was zero. The use of the Apache II scoring system contributes to improvement of clinical judgment of patients with gastrointestinal bleeding. PMID- 8351581 TI - [Use of cultured epidermal autotransplantation in a severely burned patient]. AB - In the submitted paper the authors describe in detail the administration of cultivated epidermal autotransplants (CEA in a patient with severe burns (80% of the body surface). They draw attention to several problems which occurred during treatment: a) a relatively small overall increase of CEA and the long time required for their cultivation, b) the very difficult preparation of infected wound surfaces for transplantation, c) secondary healing of CEA. The solution of these problems is according to the authors optimization of the laboratory technique of CEA cultivation and substitution of the dermal component of skin. PMID- 8351582 TI - [60 years' of the Trauma Hospital in Brno]. PMID- 8351583 TI - [Report on the activity of regional surgical societies]. PMID- 8351584 TI - An update on gastrointestinal surgery. PMID- 8351586 TI - New advances in the understanding of Barrett esophagus. PMID- 8351585 TI - Noncardiac thoracic surgery in children: an overview. PMID- 8351587 TI - Limitations and pitfalls of laser angioplasty. AB - Overall, the initial and long-term results of LABA have been disappointing. Poor initial recanalization rates and high restenosis and hemodynamic failure rates have caused investigators to reevaluate the indications for LABA. This reevaluation has resulted in an appropriate limitation of the indications for LABA. At present, LABA is probably indicated only for the treatment of patients with symptomatic, isolated arterial occlusions in whom conventional balloon angioplasty cannot be done because mechanical recanalization using a guidewire is not possible. Other uses of LABA in patients with peripheral vascular disease are discouraged and should be considered experimental. New innovations in technology, including improved arterial imaging techniques and better laser delivery systems, are required before LABA can become a standard therapy for the treatment of patients with peripheral vascular disease. A search for an "ideal" laser wavelength for arterial recanalization is futile until these developments occur. Once these innovations are in use, laser angioplasty may be an important technique in the treatment of peripheral vascular disease. This potentially valuable tool for the vascular surgeon should not be abandoned. Rather, it should be laid aside until it is better developed. PMID- 8351588 TI - Newer aspects of trauma care. PMID- 8351589 TI - Sports-related injuries to the shoulder and knee. PMID- 8351590 TI - Penile microvascular arterial bypass: indications and surgical considerations. PMID- 8351592 TI - Venous access devices: a review. PMID- 8351591 TI - Evolving management of biliary tract disease. AB - The variety of treatments available for gallstone-related problems require a multidisciplinary approach with involvement of the surgeon, endoscopist, and radiologist. Many conditions, until recently treatable only by an open operation, can now be satisfactorily dealt with by minimally invasive or endoscopic techniques. The benefits of such techniques are immediately apparent in terms of reduced hospital stay and early patient recovery. The pace of progress, particularly in the area of laparoscopic biliary surgery, is rapid and has important implications for surgical training and resources. Careful audit and prospective trials, when appropriate, are required to determine optimum treatment strategies for patients with benign biliary disease. These are exciting times in surgery, but our enthusiasm for new techniques should not cloud time-honored surgical principles. PMID- 8351593 TI - Recent advances in the management of intra-abdominal infections. PMID- 8351594 TI - Anal sphincter function: fecal incontinence and its treatment. PMID- 8351595 TI - Unsolved problems in endoscopic surgery. PMID- 8351596 TI - Proctors, preceptors, and laparoscopic surgery. The role of "proctor" in the surgical credentialing process. PMID- 8351598 TI - Management of bile leaks following laparoscopic cholecystectomy. AB - In a series of 650 consecutive laparoscopic cholecystectomies, nine bile leaks were identified (1.4%). Patients with bile leaks presented clinically at a mean of 4.9 days (range: 3-8 days) after surgery complaining of diffuse abdominal pain, ileus, and nausea. Laboratory values for complete blood counts and liver function tests were all mildly elevated. Definitive diagnosis was made on the basis of abnormal hepatobiliary scintigraphy. Management strategies included laparotomy and drain placement (n = 1), laparoscopy and drain placement (n = 3), ERCP and drainage (n = 4), and CT-guided percutaneous drainage (n = 1). When the etiology of the leakage was identified, it was most commonly either dysfunction of the cystic duct clips (n = 3) or leakage from a disrupted duct of Luschka (n = 2). The source of the remaining leaks (n = 4) was never determined. We conclude that bile leaks are an uncommon cause of morbidity following laparoscopic cholecystectomy. Diagnosis can usually be made with nuclear medicine biliary tract scans and a variety of managements alternatives are successful in treating this complication. PMID- 8351597 TI - Current dilemmas in management of common duct stones. PMID- 8351599 TI - Laparoscopic cholecystectomy for acute cholecystitis. AB - Because laparoscopic cholecystectomy reduces hospitalization time and postoperative disability, it is being offered to an increasing number of patients with symptomatic gallstones. Nevertheless, acute cholecystitis is still considered by many surgeons to be a relative contraindication. Our standard approach has been to perform laparoscopy on all patients considered candidates for cholecystectomy. From June 1990 to October 1991, the authors personally performed laparoscopic cholecystectomy on 110 patients, 29 (26%) of whom had pathologically confirmed acute cholecystitis. Of these, nine had evidence of gangrene, perforation, or abscess formation. It was necessary to convert to open cholecystectomy in four (14%) patients. In each, inflammation or dense adhesions precluded the performance of a safe operation. The hepatorenal space was drained in 12 (41%) and cystic dust cholangiograms were performed selectively. The mean operating time was 108 min. There were no intraoperative complications. One patient developed a prolonged postoperative paralytic ileus and two patients were noted to have postoperative common duct stones. There were no deaths. The average postoperative stay for laparoscopic cholecystectomy was 2.6 days. We conclude that the advantages of laparoscopic cholecystectomy can be safely and effectively extended to the majority of patients with acute cholecystitis. PMID- 8351600 TI - Safe laparoscopic cholecystectomy in a community setting, N = 762. AB - Laparoscopic cholecystectomy (LC) can be introduced into a community with morbidity and mortality rates equal to that of open cholecystectomy. The entire general surgical community of Greensboro, NC, learned the technique of LC on animal models prior to offering this innovation to the community. Over the ensuing 12 months, they served as surgeons or assistant surgeons to each other on 762 LCs with morbidity and mortality rates comparable to open cholecystectomy. This retrospective study examined the first 1 year of experience beginning 8/13/90. This work represents all of the LCs performed in Greensboro, and all of the surgeons participated in this review. All of the surgeries were done with an electrocautery and utilized a 0 degree forward-viewing scope. Cases were performed at two hospitals with a surgeon as both operator and assistant, and no effort was made to exclude high-risk or elderly patients from this procedure. Patients averaged 50 years of age and ranged from 14 to 96 years. Static cholangiograms were performed in 27% of patients. Conversion to open cholecystectomy was seen in 4.8%. There were two cardiac deaths (0.26%) and significant complications were seen in 3.4%. Seven patients required reoperations. There were no major common bile duct injuries. This retrospective review indicates that this new procedure can be introduced into a community setting by novice laparoscopic surgeons acting both as operators and assistant with a morbidity and mortality rate comparable to that reported for open cholecystectomy. PMID- 8351601 TI - Percutaneous endoscopic gastrostomy (PEG) in cancer patients. AB - Ninety-nine cancer patients underwent PEG placement attempt at Rosewell Park Cancer Institute between January 1, 1985, and December 1, 1987. Ninety-eight of these were successful and were retrospectively reviewed to determine if cancer patients constitute a high-risk group for PEG placement. Procedure-related mortality was 2% and morbidity was 19%. Morbidity of 17% was noted at less than 30 days and 2% had late complications. Six complications were considered serious with peritonitis in 3 and tube loss in 3 patients; an additional 4 patients had a failure of adequate GI tract decompression which was the indication for their PEG placement. Ascites was a major factor in morbidity with 4 of 5 patients with ascites having complications including the 2 deaths. Overall major morbidity was not increased in cancer patients without ascites including a group of patients with carcinomatosis (18 patients) and 22 patients requiring preoperative dilatation and/or tumor ablative procedures. We conclude that morbidity in cancer patients is not increased if one excludes those with ascites from the procedure. PMID- 8351602 TI - Laparoscopic-guided feeding jejunostomy. AB - Access for long-term enteral nutrition has long been the job of the surgeon. While percutaneous endoscopic gastrostomy has revolutionized the way we provide gastric feedings, jejunal access usually requires laparotomy. We have developed a technique for placing a laparoscopic guided jejunostomy. Twenty-three patients have undergone this procedure without complication. We believe this technique will be a valuable addition to the surgeon's options for obtaining enteral access. PMID- 8351603 TI - A prospective randomized trial comparing pneumoperitoneum and U-shaped retractor elevation for laparoscopic cholecystectomy. AB - Between April and August 1991, 83 Japanese patients with symptomatic gallstones underwent laparoscopic cholecystectomy in our clinics. A prospective randomized trial was carried out to examine the safety, efficacy, and complications of the two techniques, pneumoperitoneum vs an elevating method using a U-shaped retractor. Forty-two patients were randomly allocated to the pneumoperitoneum (P) group and 41 to the U-shaped retractor (U) group. These two groups were well matched with respect to age, sex, etiology, and the severity of the chronic cholecystitis. Laparoscopic resection was successful for 88.1% (37/42) in the P group and 100% (41/41) in the U group. In patients with a severe fibrotic gallbladder, the rate of success was significantly higher (P < 0.05) in the U group (100%, 6/6) than in the P group (11.8%, 1/6). In the moderately inflamed group, the operation time (mean +/- SD) was significantly (P < 0.01) less in the U group (58.7 +/- 22.7) than in the P group (87.3 +/- 18.3). With the U-shaped retractor the usual surgical instruments can be used, and a rapid and safer laparoscopic cholecystectomy can be carried out. We prefer this approach to a pneumoperitoneum for patients with an inflamed gallbladder as hospital stay and pain are minimal. PMID- 8351604 TI - Laparoscopic inguinal hernioplasty. Repair with a conventional vs a new self expandable mesh. AB - Laparoscopic hernioplasty was performed in a prospective fashion in 100 inguinal hernias in 66 patients. When available, a self-expanding prosthesis of Mersilene, strengthened with a cross- or star-shaped wire of Nitinol, was used without fixation (group B, 43 hernias). When this prosthesis was not available, a "classic" Prolene prosthesis was used, placed preperitoneally, and stapled according to the technique of Corbitt (group A, 57 hernias). This study compares the results of the two techniques. The use of a mesh-expanding Nitinol frame significantly shortens the operating time. Since two recurrences appeared in this group, we suggest that this modified mesh should also be stapled in place. PMID- 8351605 TI - Proximal gastric vagotomy by minimally invasive methods in an acute rat model. AB - In this prospective study, minimally invasive methods of proximal gastric vagotomy (PGV) were investigated in male Sprague-Dawley rats. Completeness of vagotomy by traditional operative therapy, by laser denervation of the gastric serosa, and by subserosal or transmucosal injections of chemoneurolytic agents was evaluated with postoperative Congo red testing, ulcerogenic stimulation of the gastric mucosa, and histochemical labeling of whatever vagal fibers remained in the gastric wall. Short-term results demonstrate that successful PGV can be performed with minimally invasive methods. PMID- 8351606 TI - Laparoscopy-guided intracorporeal ultrasound accurately delineates hepatobiliary anatomy. AB - The purpose of this study was to develop a technique and assess the ability of a laparoscopic ultrasound probe to delineate biliary antomy and to determine the presence or absence of duct stones. METHODS: Five pigs had ultrasonography of biliary structures and liver at laparoscopy followed by cholangiograms and anatomical dissection. Five patients had ultrasonography of the biliary tract at laparoscopic cholecystectomy. RESULTS: All animals had adequate visualization of important hepatobiliary structure, and an optimal method of accessing these structures at laparoscopy was established. Patients had ultrasonography which used methods developed in the animal trial. All had adequate visualization of the entire common bile duct confirmed by cholangiography. Limitations in demonstrating the relationship of the cystic duct to the common duct were technical and can be corrected. CONCLUSION: Laparoscopic ultrasonography has significant potential for delineation of biliary anatomy and determination of presence or absence of duct calculi. Clinical implementation could minimize the risk of iatrogenic duct injury and the need for operative cholangiography. PMID- 8351607 TI - Thoracoscopic treatment of spontaneous pneumothorax with the ENDO-GIA-Stapler. AB - Spontaneous pneumothorax carries a high risk of recurrence after treatment by intercostal drainage only. In such cases and in patients with persistent air leaks under adequate drainage we avoided correction by open thoracotomy using thoracoscopic techniques. On five patients we performed six resections of lung areas bearing blebs or bullae. An ENDO-GIA-Stapler was used for transection and closure of the lung tissue. In one patient a partial apical pleurectomy was added and in four patients an additional pleurodesis with silver nitrate was performed. An immediate air-tight suture was achieved in every case. There were no complications associated with this method. The postoperative pain and the length of hospital stay were markedly reduced compared to open thoracotomy procedures. During the follow-up period (3-7 months) no recurrence was noticed. PMID- 8351608 TI - Conversions and complications of laparoscopic cholecystectomy. Results of a survey conducted by the French Society of Endoscopic Surgery and Interventional Radiology. AB - During 1991, 41 surgeons of the French Society of Endoscopic Surgery and Operative Radiology (SFCERO) performed 3,673 cholecystectome of which 2,955 were laparoscopic. Data for those patients in whom a conversion to laparotomy was necessary or a complication occurred were collected by a retrospective multicenter survey. Conversion was performed in 142 patients (4.8%): in 106 this was due to pathology in the subhepatic space; in 36 it was because of a complication related to the laparoscopy. There were 101 postoperative complications (morbidity 3.4%): 59 biliary and 42 non biliary complications and six deaths (mortality 0.2%). There were 18 bile duct injuries, one of which led to the death of the patient. Excluding conversions to laparotomy, these figures are comparable to those for open cholecystectomy. These results define the limits and advantages of laparoscopic cholecystectomy. Conversion to laparotomy remains a wise option in cases of technical difficulty or doubtful biliary anatomy. PMID- 8351609 TI - Ultrasound in the diagnosis of roundworms in gallbladder and common bile duct. Report of four cases. AB - Four patients who complained of symptoms and signs compatible with biliary tract disease and in whom the diagnosis of gallbladder (three cases) and common bile duct ascariasis (one case) was made sonographically are reported. In two patients with gallbladder ascariasis, cholecystectomy corroborated the presence of the round-worms, and was curative. The third patient was a pregnant woman (32nd gestational week) who took piperazine citrate, and a second sonogram performed 29 days later was completely normal. The fourth patient with common bile duct ascariasis underwent choledochotomy with extraction of one ascaris lumbricoides from the common duct, and a T tube was left in place for 15 days. All patients received antiparasitics and had a favorable outcome. Ultrasonography is an important noninvasive diagnostic procedure in the work-up of these patients, who usually describe a clinical picture suggesting gallstone disease: this is especially true in the presence of pregnancy. PMID- 8351610 TI - Splenic injury and abscess complicating endoscopic retrograde cholangiopancreatography. AB - A subcapsular hematoma of the spleen was incurred during ERCP and papillotomy. This was complicated by development of a splenic abscess, which was treated by percutaneous drainage. PMID- 8351611 TI - Laparoscopic surgery in the rat. Description of a new technique. AB - We report a method of laparoscopic surgery in the rat. Our technique is illustrated by gastric fundoplication requiring two-handed dissection, suturing, and knot tying. This model for laparoscopic surgery is relatively inexpensive, can be extended to other operations, and makes use of an extensively studied animal. These factors may facilitate investigation of the physiologic effects of minimal access surgery. PMID- 8351612 TI - Problem-solving in laparoscopic surgery. AB - The advent of the laparoscopic revolution and the wider applicability of laparoscopic procedures has caused surgeons to re-think the dynamics of intraoperative problem-solving. Problems of body habitus, previous surgery, exposure, bleeding, and anesthesia, as well as the problem cholangiogram, require new and innovative approaches, a practical approach to each of these common laparoscopic problems is presented. PMID- 8351613 TI - Principles of endoscopic and laparoscopic ultrasound. PMID- 8351614 TI - Laparoscopic repair of paraesophageal hiatal hernias. PMID- 8351615 TI - The Endo clip applier--a superior extracorporeal knot pusher in disguise? PMID- 8351616 TI - Guidelines for diagnostic laparoscopy. Society of American Gastrointestinal Endoscopic Surgeons (SAGES). PMID- 8351618 TI - Guidelines for office endoscopic services. Society of American Gastrointestinal Endoscopic Surgeons (SAGES). PMID- 8351617 TI - The role of laparoscopic cholecystectomy (L.C.). Guidelines for clinical application. Society of American Gastrointestinal Endoscopic Surgeons (SAGES). PMID- 8351619 TI - Guidelines for submission of continuing medical education seeking SAGES endorsement for courses in laparoscopic surgery. Society of American Gastrointestinal Endoscopic Surgeons (SAGES). PMID- 8351620 TI - Neurosurgery in San Diego: a historical vignette. PMID- 8351621 TI - Dural carotid cavernous sinus fistula presenting as isolated oculomotor nerve palsy. AB - We report five patients with dural carotid cavernous sinus fistula presenting with isolated oculomotor nerve palsy. All patients were older women with a fistula derived from the internal carotid artery, who had early filling of the supero-posterior cavernous sinus, followed by drainage posteriorly into the inferior petrosal sinus, with low shunt flow. The hypothesized pathogenesis was nerve compression by an expanding sinus, or ischemic neuropathy secondary to venous congestion or arterial steal. Dural carotid cavernous sinus fistula must be considered in patients presenting with isolated oculomotor nerve palsy. PMID- 8351622 TI - Unilateral hydrocephalus resulting from occlusion of foramen of Monro: a new procedure in the treatment: stereotactic fenestration of the septum pellucidum. AB - Obstruction at the foramen of Monro resulting in unilateral hydrocephalus is an uncommon entity that may be caused by a wide range of lesions including tumors, vascular malformations, and inflammatory conditions. A case of unilateral hydrocephalus secondary to congenital atresia of the foramen of Monro treated with stereotactic fenestration of the septum pellucidum is presented. PMID- 8351623 TI - Sphenoid sinus mucopyocele with marked intracranial extension: a more common phenomenon in the Third World? AB - Sphenoid sinus mucoceles are rare lesions. Those with intracranial extension were thought to be extremely rare in Western literature. We encountered three such cases within 1 year. These cases were confirmed on pathological examination to be pyoceles of the sphenoid sinus, extending to the sella and suprasellar region. Bilateral exophthalmos, papilledema, and severe headache were among the most consistent findings encountered. It appears that these lesions might be more common in areas of poor socioeconomic status like Third World countries. This condition should be considered in the differential diagnosis of lesions of the sella extending to the suprasellar region. PMID- 8351624 TI - Unilateral pterional approach to bilateral cerebral aneurysms. AB - Between 1976 and 1991, we determined that 19 patients harboring bilateral supratentorial aneurysms should be approached in a single sitting through a unilateral pterional craniotomy. Using microsurgical techniques, the Sylvian cistern was opened widely to expose the aneurysms located ipsilateral to the craniotomy. These aneurysms were clipped in the usual fashion. Following clipping, a tunnel was developed over the contralateral anterior cerebral artery and over or under the contralateral optic nerve allowing access to the opposite carotid and middle cerebral arteries. The contralateral nonruptured aneurysms were clipped in a routine fashion. We were able to clip or wrap with muscle all bilateral aneurysms in 15 cases, and we have concluded that this approach can be safely employed in selected patients with bilateral supratentorial aneurysms, and thus a second craniotomy can be avoided. PMID- 8351625 TI - Malignant schwannoma of the cerebellum: case report. AB - A case of malignant cerebellar schwannoma is presented in a woman aged 61 years. A malignant schwannoma of the cerebellum has not been previously reported in the literature. The histological, immunocytological, and ultrastructural properties suggested that this lesion was a malignant, partially epithelioid schwannoma. PMID- 8351627 TI - Spinal xanthogranuloma in a child: case report. AB - A case of a patient with a xanthogranuloma in the thoracic spine is presented. Magnetic resonance imaging revealed an intradural extramedullary tumor between T6 and T9 as a low-intensity mass on both T1- and T2-weighted images. Total removal of this tumor was achieved through a laminoplastic laminectomy. Differentiation of this disease from other xanthogranulomas in the central nervous system is discussed. PMID- 8351626 TI - Congenital subclavian steal syndrome with anomaly of the aortic arch. AB - A case of congenital subclavian steal syndrome associated with an anomalous right sided aorta is reported. A 41-year-old man complaining of vertigo and a loss of consciousness was admitted. Physical examination revealed a blood pressure differential between the arms that was 20 mm Hg less in the left. Aortography showed a right aortic arch from which arose the right subclavian and both common carotid arteries. The left subclavian artery did not opacify. Right vertebral angiography showed retrograde filling of the left vertebral. A left carotid subclavian bypass was performed. Postoperatively, the patient is symptom free with equalized blood pressure. PMID- 8351629 TI - Resolution of focal CT hypodense lesions in patients with subarachnoid hemorrhage. AB - Cerebral infarction in the setting of vasospasm due to subarachnoid hemorrhage (SAH) is a known complication of aneurysmal rupture. Computed tomography (CT) has been instrumental in making this diagnosis; however, focal hypodense lesions on CT scan do not always represent infarcted tissue. Two patients are presented here who had CT hypodense lesions in regions of cerebral vasospasm following subarachnoid hemorrhage. PMID- 8351628 TI - Ultrasound-guided brain biopsy: a personal experience with emphasis on its indication. AB - Between January 1989 and June 1991, 40 ultrasound-guided biopsies of supratentorial brain lesions exceeding 15 mm in diameter were performed. The apparatus used was Berger's neurobiopsy set, intraoperative 5 = MHz transducer, and a B-mode scanner. In 38 cases (95%) the procedure provided a histological diagnosis at the first attempt; in two patients, early in the present series, biopsy was repeated by computed tomography-guided technique due to insufficient samples. Operative mortality was zero and there were no septic complications. Clinical symptoms were stationary after the procedure in 34 cases; two cases temporarily worsened due to postbiopsy edema and subcortical hemorrhage, respectively; and four other cases showed an improvement as a result of evacuation of neoplastic cysts. Histologically, there were 24 primary malignant tumors, eight low-grade glial tumors, five metastatic tumors, two abscesses, and one lymphoma. The ultrasound method for brain lesion biopsy was found to be a simple, quick, and low-cost method that gave reliable results. It is indicated for supratentorial lesions over 15 mm in diameter that do not demand absolute anatomical accuracy. PMID- 8351630 TI - Hydrosyringomyelia-Chiari I complex. Prospective evaluation of a modified foramen magnum decompression procedure: preliminary results. AB - A modified foramen magnum decompression procedure, designed to respect the subarachnoid spaces as much as possible, was prospectively evaluated in eight consecutive patients with a progressive clinical syndrome related to hydrosyringomyelia-Chiari I complex. This evaluation included quantitative clinical and magnetic resonance follow-up of at least 1 year in the first six patients and 6 months for the last two. Magnetic resonance scans at 6 months or more confirmed a persistent reduction of the hydrosyringomyelic cavity in all cases, which was associated with obvious subjective improvement. All patients have maintained this improvement. The operative technique and methods of clinical and radiological follow-up are discussed. PMID- 8351631 TI - Mycotic aneurysms of the intracavernous carotid artery. PMID- 8351632 TI - Contributions to a seminar on the history of neurosurgery on the West Coast. PMID- 8351633 TI - The development of neurosurgery in northern California. PMID- 8351634 TI - History of neurosurgery in Oregon. PMID- 8351635 TI - Brain tumors always die: a satiric parade. 1937. PMID- 8351636 TI - [Sports capacity of patients with scoliosis]. AB - The burden of sport of patients with scoliosis depends on the age, the expected progredience of the deformity and the attained deformation. In children and teenagers treated with an orthesis, total prohibition is not appropriate. All kinds of sport not involving any risk of injury to the participant or the patient wearing an orthesis can be practised. The orthesis may be removed only during swimming. For patients with a fused spine the number of the remaining lumbar moving segments and the deformity are essential for the exercise load. If there are less than three free lumbar segments all kinds of sport with axial and rotationary burdens are not to be recommended. If the spinal bending is more than 50 degrees (Cobb) the limitation of the cardiopulmonary ability is even more severe. PMID- 8351637 TI - [Current aspects of meniscus transplantation]. AB - Meniscus transplantation is a common procedure for some orthopaedic surgeons all over the world. Deep frozen as well as freeze-dried meniscal allografts were transplanted. Reconstruction of the knee ligaments after meniscectomy as well as surgical therapy of osteochondral defects of the knee joint after meniscectomy are some of the indications for meniscus transplantation. Our own long-term results of freeze-dried meniscus, however, showed a degeneration of the transplants after two years up to a meniscus regenerate. Deep frozen meniscus transplants may be contaminated with virus (e.g. Hepatitis, AIDS). Taking the infrapatellar fatty pad for meniscal replacement (as suggested by Lexer) we saw only a weak meniscus like tissue after the first year postoperatively. The tendon meniscus by means of autologous tendon for meniscus replacement may be an alternative procedure. Therefore, meniscus transplantation cannot be recommended at present as a standard procedure for reconstruction of the knee joint. PMID- 8351638 TI - [Osteochondrosis dissecans of the knee and sports]. AB - Osteochondritis dissecans (O.d.) of the knee is a common disease, but the aetiological factors are still controversial. With a follow-up examination of 97 surgically treated patients (109 lesions) we looked for the influence of preoperative sports activities as a possible aetiological factor. Most of the patients complained first symptoms at puberty age between 10 and 15 years, girls with a mean age of 12.4 years and boys with a mean age of 15 years. Because of that, humoral factors are supposed to have influence on the onset of this lesion. Also patients with O.d. of the knee demonstrated a high rate of sports activities and/or trauma prior to the onset of symptoms. There was also a good correlation between lesions at the medial condyle with varus malalignment. Additionally, in most of the patients a high grade of general ligament laxity could be observed at the follow-up examination. It seems that biomechanical factors have an important aetiological influence on the initiation of O.d. at the knee. At the date of follow-up examination all patients reported on a minor sports activity in comparison to sports activities prior to the onset of symptoms. The amount of postoperative sports activities depends on the level of the resulting Lysholm score and on the grade of osteoarthritis. PMID- 8351639 TI - [Stress fractures of the navicular bone--biomechanical and densitometry studies]. AB - One of the most important pathogenetic mechanisms regarding stress fractures of the navicular bone lies in the hyperpronation movement of the foot. For recording the impacts of the pronation movement on the talonavicular joint, stress and pressure experiments are carried out and the radii of curvature as well as the bone density are measured. The stress experiments show a rotation movement of the talar head in a medioplantar direction of about 20 degrees. The radii of curvature of the articulating joint surfaces do not differ to a great extent. A possible incongruency in the joint therefore has to be attributed to the rotation movement of the talus during pronation of the foot. The pressure experiments show a very irregular distribution of pressure in the joint presenting a lateral and medial pressure maximum. Fractures preferably occur in the area in between these maxima. Areas of high subchondral bone density in the densitometric results are found in the central part of the talar head as well as in the medial part of the navicular bone. Within the functional adaptation the distribution of bone density expresses the rotation movement of the talus during pronation of the foot. PMID- 8351640 TI - [Overuse syndrome in ballet: study of the effect of a tape bandage of the upper ankle joint with motion analysis]. AB - In six ballet dancers with overuse syndromes of the foot a study on the effect of taping on stabilisation, proprioception and muscular activity was performed. By using synchronous surface electromyography and 3-dimensional motion analysis three standard ballet positions without and with applied tape were performed. Muscular activities of pronator muscles (peroneus longus) and supinator muscles (tibialis posterior) were recorded. EMG measurements showed significant differences between patients with stable or unstable ankles and painful or pain free feet. Applying tape led to significant changes of muscle activities in height and antagonist reflex patterns. These changes were highest in dancers with unstable ankle joints and metatarsalgia. PMID- 8351641 TI - [Traumatic occlusion of the internal carotid artery as an injury sequela of soccer]. AB - The largest number of people engaged in sports in Germany play football. There were about 1.5 million sports injuries annually in the previous Federal Republic of Germany. Steinbruck (5) reported that the highest number was found in football players, in whom the injuries of the legs are most frequent. Head and vascular injuries are unusual and seldom in football players. We report on the case of a patient who received an elbow blow from his opponent. He developed a stroke with hemiparesis because of a traumatic dissection of the A. carotis interna. PMID- 8351642 TI - [The special case]. PMID- 8351643 TI - Josef Warkany 1902-1992. PMID- 8351645 TI - Embryonic development of the mammalian caudal neural tube. AB - In the literature, some controversy still exists about the embryonic developmental processes involved in the formation of the caudal neural tube. Therefore, a three-dimensional and histological study concerning the normal development of the caudal neural tube was performed on both mouse and human embryos. Three developmental processes can be distinguished in caudal neural tube development: caudal neuropore closure, secondary neurulation, and degeneration and differentiation of the secondary neural tube. Caudal neuropore closure occurs at the level of somite 32-34 in both species. Therefore, primary neurulation leads to the formation of all spinal cord segments and ganglia. Secondary neurulation involves cell deposition from a cluster of neurectodermal cells at the caudal end of the closed neural tube, directly around a lumen, the lumen always in contact with the lumen of the primary neural tube. This process leads only to the formation of the primordia of the filum terminale and ventriculus terminalis and, possibly, part of the conus medullaris. Secondary neurulation is followed by a period characterized by degeneration and differentiation of the secondary neural tube. Its lumen and neural tissue will disappear, whereas part of the secondary neurectodermal cells differentiate to a fibrous layer comparable and continuous with the marginal layer of the primary neural tube. This fibrous layer represents the future filum terminale. The embryological processes indicated above can be helpful in the interpretation of congenital anomalies affecting the caudal spinal cord and spine. PMID- 8351644 TI - Hydantoin syndrome with holoprosencephaly: a possible rare teratogenic effect. AB - We report on a newborn girl with lobar holoprosencephaly and clinical signs of hydantoin syndrome. During pregnancy the mother was treated with diphenylhydantoin and primidon for psychomotor and petit mal seizures. The possible relationship between hydantoin syndrome, holoprosencephaly, and maternal intake of anticonvulsants during pregnancy is discussed. PMID- 8351646 TI - Developmental toxicity evaluation of diethyl and dimethyl phthalate in rats. AB - Diethyl phthalate (DEP) and dimethyl phthalate (DMP), phthalic acid ester (PAE) plasticizers, were evaluated for developmental toxicity because of reports in the literature that some PAE were embryotoxic and teratogenic. A previous study (Singh et al., '72) suggested that an increased incidence of skeletal defects in rats might result from gestational exposure to DEP (0.6-1.9 g/kg) or DMP (0.4-1.3 g/kg), ip, on gestational days (gd) 5, 10, and 15. In the current study DEP (0, 0.25, 2.5, and 5%) or DMP (0, 0.25, 1, and 5%) in feed (approximately 0.2-4.0 g/kg/day) were supplied to timed-mated rats from gd 6 to 15. Treatment with 5% DMP resulted in increased relative maternal liver weight. Also, animals exhibited reduced body weight gain during treatment (5% DEP or DMP) and during gestation (5% DEP). Weight gain corrected for gravid uterine weight was also reduced in animals fed 5% DEP. However, high-dose treatment with either DEP or DMP resulted in changes in food and water consumption paralleling the body weight reductions, suggesting that apparent toxic effects on maternal body weight may reflect PAE/feed unpalatability. Treatment with 2.5% DEP resulted in only transient changes in body weight during early treatment. The only maternal effects at 0.25 or 1% DMP were minor changes in food and/or water consumption, and there were no effects at 0.25% DEP. Thus, the NOAELs for maternal toxicity were 1% DMP and 0.25% DEP. In contrast to the observed maternal toxicity, there was no effect of DEP or DMP treatment on any parameter of embryo/fetal development, except an increased incidence of supernumerary ribs (a variation) in the 5% DEP group. These results do not support the conclusion of other investigators that DEP and DMP are potent developmental toxicants. Rather, they suggest that the short-chain PAE are less developmentally toxic than PAE with more complex substitution groups, e.g., di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate, and butyl benzyl phthalate. PMID- 8351647 TI - The effect of tolbutamide on rat embryonic development in vitro. AB - Tolbutamide (TOLB) is a sulfonylurea used to treat non-insulin-dependent diabetes mellitus and is a suspected teratogen. However, it is not possible to discriminate between potential teratogenic effects of TOLB and malformations produced by either drug-induced hypoglycemia or the diabetic state itself. We examined the direct effect of TOLB on rat embryos cultured in a rodent whole embryo culture system. CD strain rat embryos were cultured for 48 h beginning on day 9 of gestation (plug day = day 0). Tolbutamide was added at various concentrations (90-3,600 microM). At the end of culture, viable embryos were examined for morphological score, number of somite pairs, crown-rump and head lengths, and DNA and protein content. Tolbutamide produced dose-related decreases in all endpoints at concentrations (2,250-3,600 microM) which are two to four times the human therapeutic concentration. Sera from TOLB-treated rats were adjusted to contain equal concentrations of glucose and insulin and then used for embryo culture. Serum from TOLB-treated rats had no observable effect on embryonic development. The mechanism for the embryotoxic effect of TOLB is unknown; however, the drug was previously demonstrated to alter activity of purified yeast glutathione reductase (GR). Because GR may be important for normal embryonic development, the effect of TOLB on this enzyme activity in cultured rat embryos was evaluated. Tolbutamide (2,700 microM) reduced embryonic GR activity by 35-57%. These results indicate that TOLB has a direct embryotoxic effect at levels 2 to 4 times the usual therapeutic serum concentrations on developing rodent embryos which may be mediated by GR inhibition. PMID- 8351648 TI - Potentiation of triamcinolone-induced cleft palate in mice by maternal high dietary fat. AB - This study investigated whether the current range in dietary fat levels, which has arisen partly in response to some major health concerns, would affect frequency of congenital anomalies if continued into the period of early pregnancy. The effect of 5.6%, or 48% of calories from fat in the maternal diet, was tested on pregnant strain CD-1 mice injected with triamcinolone in doses of 0.01 mg, 0.02 mg, 0.04 mg, or 0.06 mg per day on days 11 through 14 of gestation. Frequency of cleft palate increased with increasing doses of triamcinolone, with clefts of the palate being rare at the two lower doses. No clefts appeared without triamcinolone on either diet. In combination with triamcinolone treatment, 226 fetuses exposed to a maternal low fat diet had normal palates and 86 had cleft palates. With exposure to high fat, 186 fetuses had normal palates and 101 had cleft palates, which was a significant increase in clefting (p < 0.05). Also, the latter group showed a greater degree of retardation in palate development (p < 0.05). Thus both a greater frequency and a more severe form of clefting support the conclusion that high dietary fat potentiated the cleft palate-producing effects of triamcinolone in mice. PMID- 8351649 TI - Evaluation of developmental toxicity of coniine to rats and rabbits. AB - Conium maculatum (poison hemlock, CM) is teratogenic in several domestic species, presumably due to its piperidine alkaloids, including coniine, which has been verified to be teratogenic in cattle. Coniine/CM teratogenicity culminates in production of arthrogryposis. The purpose of this study was to evaluate coniine induced teratogenicity in two laboratory animal species, Sprague-Dawley rats and New Zealand white rabbits. Pregnant rats were given coniine (25 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 16-18. Pregnant rabbits were given coniine (40 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 20-24. Rats were killed on day 19 and rabbits on day 29. Fetuses were immediately removed, weighed, and examined for external abnormalities. Alternate fetuses were either stained for skeletal examinations with alizarin red-S or fixed in Bouin's solution for visceral examination. Symptoms of maternal intoxication due to coniine administration were observed in both the rat and the rabbit, and higher doses were uniformly lethal. Rabbits treated with coniine appeared to lose more weight and eat less than controls, but there was no statistically significant difference between groups. Fetal weights were significantly lower in coniine-exposed rat and rabbit fetuses indicating fetotoxicity. The only statistically significant treatment-related visceral or skeletal malformation was a reduction of cranial ossification of rabbit fetuses, probably related to maternal toxicity. Coniine-exposed rabbit litters tended to be affected by arthrogryposis (no bony deformities noted on skeletal exam) more than controls (2/6 vs. 0/9). PMID- 8351651 TI - They're outta here ... or are they? PMID- 8351650 TI - Glucose causes lengthening of the microvilli of the neural plate of the rat embryo and produces a helical pattern on their surface. AB - Prominent microvilli have been observed on the surface of neural plates in the embryos of many species. Since glucose is the main source of energy for embryos before neural tube closure and the onset of vascular circulation, it was of interest to study the relationship between these microvilli and glucose utilization in the neural plate. By applying microdrops of amniotic fluid to chemstrips, which colorimetrically measure glucose by glucose oxidase reaction, we determined that day 10 rat amniotic fluid glucose level was 31.6 +/- 1.6 mg/dl. On day 10 and within about 20 min from removal of the decidual sites, no glucose was found in the amniotic fluid. By use of a scanning electron microscope, the microvilli of the day 10 neural plate were found to have a 10 fold increase in length during a 40-min exposure to Hanks' solution at 21-23 degrees C. Similarly exposed embryos in Hanks' without glucose did not have microvillus elongation. However, under whole embryo culture conditions at 38 degrees C no extension of the microvilli was found. In the closed neural tube of the day 10 embryo, the microvilli were stubby and did not elongate with glucose exposure. Similarly, day 11 and 14 embryos had short microvilli which did not elongate with direct exposure to glucose at 21-23 degrees C. The short microvilli on the surface of the closed neural tube on day 11, 14, and 16 were associated with low glucose concentrations in the neural tube fluids. By use of a field emission scanning electron microscope, the surfaces of the microvilli in the extended position were seen to be covered by a right-handed helical array of globular objects the size of large molecules. The findings support the hypothesis that microvillar length may modulate glucose uptake. Shortening is associated with low concentrations of glucose in closed neural tubes, and lengthening occurs at glucose exposures of 100 mg/dl. PMID- 8351652 TI - Texas short on occupational health care, study shows. PMID- 8351653 TI - Costs of on-the-job injuries high in Texas. PMID- 8351654 TI - Physicians must report elder abuse. PMID- 8351655 TI - Betty Anne Halpern, MD. Disc jockey doctor speaks truth over airwaves. PMID- 8351656 TI - Can a consultant help your practice chart a better course? PMID- 8351657 TI - Governor signs immunization bill. PMID- 8351658 TI - Lawsuit abuse takes toll in Rio Grande Valley. PMID- 8351659 TI - HCFA begins inspections of Texas physicians' office laboratories. PMID- 8351660 TI - New director, health commissioner talk about Texas Medicaid. Interview by Mark Richardson. PMID- 8351661 TI - Flawed malpractice study finds unjustified payments are uncommon. PMID- 8351662 TI - Coronary artery endarterectomy: a method of myocardial preservation. AB - The lack of acceptable coronary arteries for grafting often causes the cardiac surgeon considerable problems in treating patients with severe coronary artery disease. By combining the standard approach of coronary bypass surgery with coronary endarterectomy and with retrograde coronary sinus cardioplegia perfusion, we can achieve a longer ischemic period and can flush the debris from the coronary arteries in a retrograde fashion. Using this approach, we managed 72 patients with near inoperable coronary artery disease. One third of these patients required endarterectomy of more than one vessel. A higher than expected number of patients had diabetes mellitus. The left coronary artery system required endarterectomy in almost 60% of patients, much higher than percentages reported in other series of patients. The mortality rate in our patients who underwent the left system endarterectomy was 5.7%. Endarterectomy must be considered an adjunct in the management of high-risk patients with severe coronary artery disease. PMID- 8351663 TI - Jones' fracture. AB - The Jones' fracture is defined as a transverse fracture of the proximal fifth metatarsal diaphysis within 1.5 cm of the tuberosity. It is classified radiographically as acute, delayed union and nonunion. Some orthopedists also have added a classification of stress fractures. The best form of treatment is based on the presence or absence of medullary sclerosis adjacent to the fracture site. In addition, the prescribed treatment must be adhered to by the patient to prevent increased morbidity associated with this fracture. PMID- 8351664 TI - Physicians should be able to dispense drugs to patients. PMID- 8351665 TI - Extended treatment with diltiazem hydrochloride successful. PMID- 8351666 TI - [Inventa nova--mile markers in the history of cardiology]. PMID- 8351667 TI - [Epidemiologic aspects of heart failure: incidence, causes and follow-up]. AB - Congestive heart failure can develop as a complication of virtually all forms of heart diseases. Depending on diagnostic criteria, the figures for prevalence and incidence differ markedly. The frequency of congestive heart failure increases with age and doubles in each life decade. In the United States the prevalence of 1% and for Great Britain 0.4% respectively have been calculated. In the highest age groups up to 90 new cases/1000 population per year can be observed. As a contribution to decreasing mortality of acute myocardial infarction and better treatment of high blood pressure as well as congestive heart failure the number of patients in heart failure have increased substantially. In contrast to the Framingham Study, nowadays coronary artery disease is the most prevalent etiology of congestive heart failure followed by hypertensive heart disease. In younger patient groups with advanced heart failure, like heart transplant recipients, cardiomyopathies are the main etiologic factor. Heart failure is the leading factor for emergency admissions to hospital in adult internal medicine. The main reasons for decompensation are acute ischemic syndromes for acute congestive heart failure and compliance problems for chronic congestive heart failure. The natural history of congestive heart failure is characterized by a marked progression, increasing with the severity of heart failure. In parallel, mortality increases, too. A variety of clinical, hemodynamic neurohumoral and electrophysiologic factors have been described as independent factors predicting prognosis. 30 to 50% of heart failure patients die a sudden death as compared with progressive pump failure or infectious complications in the others. PMID- 8351668 TI - [Pathophysiology of heart failure: peripheral vascular and muscular mechanisms]. AB - Exercise tolerance in patients with congestive heart failure correlates poorly with measures of systolic left-ventricular function and is determined by disturbances of the regulation of skeletal muscle perfusion and structural and metabolic changes of skeletal muscle itself. The increase in minimal vascular resistance in skeletal muscle is due to increased activities of the sympathetic nervous system, the renin-angiotensin and vasopressin systems and decreased and increased endothelium-mediated vasodilation and vasoconstriction, respectively. In addition, skeletal muscle atrophy, decreased oxidative capacity and a relative increase of easily fatiguable glycolytic muscle fibres also contribute to the reduction of exercise tolerance. The disturbances of skeletal muscle perfusion and changes of skeletal muscle are at least in part reversible by vasodilator therapy or, in the extreme situation, by cardiac transplantation. PMID- 8351669 TI - [Clinical diagnosis of heart failure]. PMID- 8351670 TI - [Doppler echocardiography diagnosis in heart failure]. AB - The evaluation of heart failure is one of the most common reasons for echocardiography in the adult population. Within this context, Doppler echocardiography as a noninvasive diagnostic procedure is able to provide immediate and relevant information on functional and structural changes underlying the clinical syndrome of heart failure. Analysis comprises global left and right-ventricular systolic function, regional wall motion and diastolic function. Evidence of normal systolic left-ventricular function has been reported in up to 30% of the patients with clinical signs of heart failure, suggesting abnormal diastolic function as the origin for the symptoms of heart failure. Therefore, noninvasive assessment of heart failure by Doppler echocardiography must include analysis of systolic as well as diastolic left-ventricular function. PMID- 8351671 TI - [Diagnosis of heart failure with radionuclide ventriculography]. AB - Radionuclide ventriculography is presented as noninvasive scintigraphic method to assess the pump function of the heart. Its role in diagnosis and prognosis of congestive heart failure is described. Advantages and limitations of this technique as compared to echocardiography are discussed, and the importance of left-ventricular ejection fraction in the evaluation of congestive heart failure is critically reviewed. PMID- 8351672 TI - [Hemodynamics in heart failure: systolic and diastolic dysfunction]. AB - Cardiac insufficiency is hemodynamically characterised by reduced cardiac output and increased diastolic filling pressure at rest and/or during physical activity. The increase in diastolic filling pressure compensates cardiac output and is either a result of increased initial tension of muscle fibers (Frank-Starling's Law) or a sign of decreased myocardial compliance. Increased initial tension of muscle fibers is a sign of systolic insufficiency, whereas reduced ventricular compliance indicates a disorder of diastolic ventricular function. In systolic insufficiency (= systolic dysfunction) a decrease in the ventricular ejection fraction is important, as is an increase in filling pressure. In diastolic congestive heart failure (= diastolic dysfunction) a reduced ventricular compliance with normal stroke function is typical. PMID- 8351673 TI - [Arrhythmias and heart failure]. AB - Numerous factors contribute to the genesis of arrhythmias and sudden cardiac death in patients with congestive heart failure. Fibrosis of myocardium, ischemia, dilatation of the ventricles and atria, electrolyte imbalance, and neurohumoral factors are examples. Various drugs used in the treatment of congestive heart failure can also precipitate serious arrhythmias. The role of antiarrhythmics, including amiodarone, is still controversial. Judicious antiarrhythmic therapy involves weighing potential benefits of such therapy against risks, such as worsening heart failure or proarrhythmia. In patients with heart failure antiarrhythmic drugs should only be used for symptomatic arrhythmias. Low-dose beta-blockade offers a promising measure for the prevention of sudden cardiac death even in patients with symptomatic congestive heart failure. PMID- 8351675 TI - [Indications for heart transplantation, preoperative assessment and treatment]. AB - Heart transplantation [HTx] is a therapeutic option for an end-stage congestive cardiomyopathy. At the present time five and ten years' survival results after cardiac transplantation can be compared to those of coronary bypass surgery in patients with a three-vessel disease. Ten-year survival after coronary surgery in patients with a three-vessel disease and impaired left-ventricular function is 64%, without decreased left-ventricular function 72%, and after HTx between 60 and 70%. In spite of good results HTx remains a therapeutic possibility only for well-selected candidates with an expected survival of less than twelve months. Symptoms and signs for a poor prognosis are: functional NYHA-class III-IV, cardiothoracic ratio > 0.55, walking distance of less than 300 m in the 6-minute walk test, VO2 max. of < 14 ml/kg, cardiac index < 2.25 l/min/m2, pulmonary capillary wedge pressure > 16 mmHg. A syncope of any origin is, in patients with functional class III-IV, associated with a 1-year sudden-death incidence of 45%. Because of a high daily variability, ventricular ectopy alone is of limited prognostic value. Secondary pulmonary hypertension is a common finding in end stage congestive heart failure. A mean pulmonary artery pressure above 55 mmHg and a transpulmonary gradient of > 12 mmHg are associated with a poor prognosis. If pulmonary vascular resistance exceeds 4 Wood units (320 dyn.sec.cm-5), reversibility has to be proved, using sodium nitroprussid or prostaglandine E1. An irreversible pulmonary vascular resistance above 8-Wood units (640 dyn.sec.cm 5) is an absolute contraindication for HTx; lung or heart-lung transplantation are the only PMID- 8351676 TI - [Therapeutic potential of Ro 5-3335. New active benzodiazepine in vitro against HIV-1 viruses resistant or non-resistant to AZT]. AB - Ro 5-3335 is a new benzodiazepine highly active in vitro (IC50 = 0.1-1.0 microM [corrected]) against HIV-1 viruses of AIDS resistant or non-resistant to zidovudine (AZT). It is also active against HIV-2. Ro 5-3335 is original by its mechanism of action, acting on the trans-activation factor of transcription (TAT) and non on the reverse transcriptase. Such as, it could prevent proviral DNA to express in both evolutive and silent AIDS resistant or non-resistant to AZT or to other anti-reverse transcriptase series. In addition, in antagonizing extracellular TAT's actions, Ro 5-3335 could alleviate the syndrome commonly associated with AIDS as Kaposi's syndrome. In rodent test, Ro 5-3335 has no diazepam-like central effects and presents in comparison to AZT a more favorable therapeutic index. In dog, the elimination half-life, peak concentration and availability are 2 h, 0.8 microM and 85% respectively, after a 1 mg.kg-1 oral dose of Ro 5-3335. Theoretically, Ro 5-3335 and now its analogue Ro 24-7429 seem to possess all virtues to antagonize evolutive and latent AIDS. Its arrival is timely to cope with the ever increasing resistance phenomena, lengthy development of AIDS vaccines, exponential contamination of populations worldwide and last but not least possibly to impede evolutions of the disease. Ability to manipulate TAT mediated activation of HIV-1 genes paves the ways to study conceivable corrections of abnormal gene expressions of neurotransmitters, hormones, oncogenes and key enzymes. PMID- 8351677 TI - [Posology of analgesics in patients with kidney failure]. AB - Doses and dosing interval of analgesic drugs in renal failure are not always available in the data sheet compendium. The aim of the article is to analyse literature references and to present main pharmacokinetics modifications for each analgesic drug in renal failure. Pharmacokinetics parameters, doses and dosing intervals depending on creatinine concentrations are presented for each drug in a table. PMID- 8351674 TI - [Drug therapy of heart failure]. AB - The amelioration of symptoms and the improvement of long-term prognosis are the main objectives of drug treatment in congestive heart failure [CHF]. Digitalis, glycosides and diuretics can reduce dyspnea and increase exercise tolerance, while their influence on the course of the cardiac failure remains uncertain. Vasodilators, ACE inhibitors in particular, have in contrast not only the desirable symptomatic and hemodynamic effects, but they also delay the deterioration of LV dysfunction and reduce cardiac mortality. Vasodilators, therefore, became first-line drugs in all stages of CHF. In patients with moderate to severe heart failure the addition of diuretics and also of digoxin is usually required. Pharmacological effects, dosage, side effects and specific indications of the various drug groups in CHF are discussed. PMID- 8351678 TI - Pharmacokinetics of prazosin administered as gastro-intestinal-therapeutic systems to 24 healthy volunteers. AB - Pharmacokinetics of prazosin was investigated after single dose administrations of four different formulations, according to a randomized trial, to 24 young healthy volunteers: immediate release tablets (3 x 1 mg) used as reference (Treatment A), two new Gastro-Intestinal-Therapeutic-Systems (GITS) containing 2.5 mg (Treatment B) and 5 mg (Treatment C) of prazosin, and a traditional sustained release formulation (4 mg, treatment D). Relative bioavailability of prazosin administered as GITS was only 49.4 +/- 19.5% (B) and 45.5 +/- 18.7 (C) versus 73.8 +/- 13.9% (D) (area under the curve normalized at 3 mg dosing); but absorption was sustained and plasma concentrations were maintained at a virtually constant level for a time period close to 24 h. As a result, mean residence time (MRT) of prazosin was considerably increased after GITS administration: 21.6 +/- 1.0 h (B), 22.5 +/- 1.6 h (C) instead of 5.9 +/- 0.2 h for the reference formulation (A) and 10.8 +/- 0.8 h for the traditional sustained release formulation (D). Although extrapolation to multiple dosing situations is difficult, this study demonstrates the potential suitability of prazosin GITS for once daily administrations. PMID- 8351679 TI - [Effect of dimethicone on pharmacokinetics and pharmacodynamics of ethyl biscoumacetate]. AB - The influence of dimeticone (Gel de Polysilane Midy) on the pharmacokinetics and pharmacodynamics of oral ethyl biscoumacetate was studied in 6 healthy volunteers in a randomised single dose, two-way cross-over study. Each volunteer received at one week interval a single dose (300 mg) of ethyl biscoumacetate, either alone or with dimeticone. Ethyl biscoumacetate levels were measured in plasma for 24 hours. Pharmacodynamic parameters were measured for 96 hours. Ethyl biscoumacetate peak concentration was significantly higher when administered with dimeticone (40.3 +/- 25.3 mg/l vs 31.0 +/- 25.7 mg/l; p = 0.031), without significant change in the area under curve. Other pharmacokinetic and pharmacodynamic parameters did not differ significantly. The slight increase of the ethyl biscoumacetate bioavailability with dimeticone in repeated dosing might have pharmacodynamic consequence; a clinical trial should address this question. PMID- 8351680 TI - [Economic aspects of pharmacovigilance in the pharmaceutical industry]. AB - The economical aspects of pharmacovigilance in the pharmaceutical industry can be assessed by two ways. First the balance between cost of avoiding adverse drug reactions (ADR) and cost of ADR should be evaluated during the development. The company will have to take into account both efficacy and safety of its compound. However if it increases the costs of avoiding ADR it will reduce the costs of avoiding ADR occurring after commercialisation. On the other hand the cost of side effects of a marketed compound can also be appreciated. This assessment will always have to be comparative with an other drug and to take into account the benefit of both drugs, if their efficacy is not deemed identical. PMID- 8351682 TI - [Drugs involved in toxic epidermal necrolysis (Lyell's syndrome)]. AB - Drug-induced toxic epidermal necrolysis (Lyell's syndrome) is a rare, potentially lethal disease that is characterized by the sudden necrosis of the epidermis and frequently associated with mucous and systemic involvement. Even though the etiology of the disease is probably multifactorial (including viral infections and anomalies of drug metabolism), its iatrogenic origin is the principally recognized cause. We have drawn up a substantial list of the culprit drugs showing their frequency of involvement in the syndrome. PMID- 8351681 TI - [Acute toxicity of zidovudine. Analysis of the literature and number of cases at the Paris Poison Control Center]. AB - 13 cases of zidovudine overdosage have been previously published; 30 have been notified to Paris Control Poison Centre up to January 1991. This analysis shows that acute toxicity appears infrequent and mild when ingested dose is lower than 25 gr. However it appears from this series that an haematologic monitoring is needed because of the risk of myelosuppression. PMID- 8351683 TI - [Evaluation of ten years of pharmacovigilance of antihypertensive drugs in the Toulouse University Regional Hospital Center (1981-1990)]. AB - The eighties were characterized by the introduction of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) in the treatment of arterial hypertension. The present study investigates the side effects of antihypertensive drugs in the Toulouse University Hospital (France) between 1981 and 1990. Most of the side effects involved ACEI (45%), CCB (22%) and diuretics (18%). Central antihypertensive agents and beta-blocking drugs were involved in 8 and 9% of side effects respectively. During these 10 years, 197 side effects were reported in our hospital (3300 beds). Some of them were found more frequently: renal insufficiency (15%) or cough (9%) with ACEI, constipation (3%), gingivitis (1%) or lower limb oedema (4.5%) with CCB, hemolytic or autoimmune anemia (2.5%) and confusional state (1.5%) with central antihypertensive agents, nightmares (1.5%) with propranolol. The most frequently side effects were dermatological (20%), hydroelectrolytic (10%) and neuropsychiatric (9.6%) disturbances. In spite of the methodological problems of this kind of study (retrospective evaluation, under-notification of the side effects and different scores of imputability), these data indicate the most frequently observed side effects of antihypertensive agents during the eighties. It allows to estimate an approximate frequency of these side effects: among the antihypertensive drugs, CCB and diuretics seems the less frequently involved in the occurrence of reported side effects. PMID- 8351684 TI - Trends in the supply and use of lipid-lowering drugs in Spain, 1983 through 1991. AB - Trends in the supply and use of lipid-lowering drugs in Spain were studied throughout the period of 1983-1991. Although the supply of such drugs remains excessive, a trend towards more rational standards has been apparent: 20 specialties out of 53 existing in 1983 have been withdrawn (10 fixed-dose combinations and 10 obsolete drugs). The overall use of lipid-lowering drugs rose from 2.51 DDD/1000 inhab/day in 1983 to 8.47 DDD/1000 inhab/day in 1991. The increase was mostly attributable to the subgroup of fibric acid derivatives (1.23 DDD/1000 inhab/day in 1983 and 6.14 in 1991). The bile acid sequestrants accounted for a small fraction of the overall use (0.23 DDD/inhab/day in 1991), in spite of its increasing consumption. The use of the two subgroups, nicotinic acid derivatives and fixed-dose combinations, has declined. The introduction into the market of HMG-CoA reductase inhibitors in 1991 contributed to the increase of the overall use in 1.28 DDD/1000 inhab/day but it seems not to have any negative influence on the use of other subgroups. Although the prevalence rates of hypercholesterolemia are similar, the use of lipid-lowering drugs in 1991 in Spain was 3 to 8 times higher than that of the Nordic countries. In conclusion, our data suggest that lipid-lowering drugs are highly used in Spain, at least in comparison with other western countries, and that the pattern of drug use is not in accordance with international recommendations. PMID- 8351685 TI - [Measurement of cutaneous blood flow by laser Doppler velocimetry. Importance of probe effect and solvent effect after topical application]. AB - A comparative methodological study of the probe and/or vehicle effects was performed in Human volunteers with two laser Doppler velocimeters (L.D.V.): Laserflo BPM 403, T.S.I., U.S.A. and Periflux PF2B, Perimed, Sweden. Individual variations of skin blood flow are great (up to 1,400%); this could be related to spontaneous variations and/or to the occlusive effect of the probe. Skin blood flow was significantly increased in 35% of the subjects after the application of the probe alone, and in 70 to 90% of the cases after topical application of water or ethanol (20 to 50 microliters). Lag times before vasodilatation measured only when the probe was applied on the skin were between 7.4 and 27 minutes, they were reduced between 5.2 and 8.3 minutes when the vehicles were applied. These data suggest that in any protocol for L.D.V. determination an absolute control and a vehicle control should be included to evaluate objectively topical vasoactive drugs. PMID- 8351686 TI - [Commentary: has patch-testing the value of challenge test in dermatology?]. PMID- 8351687 TI - [Bullous iodides: unusual iatrogenic pathology]. PMID- 8351688 TI - Fluoxetine-related indifference and akathisia. A case report. PMID- 8351690 TI - [Fatal adverse effects. Experience of the Midi-Pyrenees Pharmacovigilance Center]. PMID- 8351689 TI - [Generalized epilepsy induced by trazodone]. PMID- 8351691 TI - Study of cyclosporin A blood level during the early post-liver-transplantation period. AB - Correlations between acute rejection rate, cyclosporin A(CsA) blood level and CsA dose were studied in a group of 58 patients for 1 month following liver transplant. Therapy included prednisolone, azathioprine and CsA administered by continuous IV infusion. Blood CsA levels were measured by high performance liquid chromatography. No patient required renal dialysis. An acute rejection episode was recorded in 24 patients (group 1) between days 4 and 28 (mean 8 days), while 34 patients (group 2) showed no signs of rejection. A significant difference was observed (p < 0.05) between blood CsA levels (mean +/- SEM over the 6 days preceding the rejection episode in group 1 patients, and the first 6 postoperative days in group 2 patients (101 +/- 7 vs 121 +/- 5 ng/ml). The mean daily dose of CsA calculated over the same time period was significantly lower (p < 0.001) in group 1 patients (46 +/- 2 vs 60 +/- 2 mg/day). In addition, over the 8 days following surgery, only 54% of patients in group 1 attained a mean blood CsA level of a least 100 ng/ml, compared to 94% in group 2. PMID- 8351692 TI - [Work loss and depression. Impact of fluoxetine]. AB - The goal of our study was to explore the impact of various antidepressant drugs on the relative risk of work loss in depressed patients. 1,852 depressed patients (DSM III-R) were observed using a "cross-sectional" design. Patients were included into five groups: patients without antidepressant treatment, patients treated with one of the main antidepressant drugs in France (amineptine amitriptyline, clomipramine and fluoxetine). Primary variables were the depression intensity (Hamilton scores) and job status (work loss). The other parameters (clinical, demographic, economic, therapeutic) were used as potentially predicting variables. Data have been collected through a network of 295 physicians (GP, Psychiatrists). The main socio-demographic characteristics of treated and untreated depressive patients, either working or absent from work, were predominantly female and city dwellers. A significant difference was found between working patients and work loss in terms of professional characteristics, i.e. type of employment (p < 0.001), type of employer (p < 0.05), level of responsibility (p < 0.01) and type of remuneration (p < 0.01). We found a positive correlation between depression severity and the risk of work loss (R2 = 0.86, p < 0.001). This risk was significantly lower with fluoxetine compared to other treatments. Pooling these data with data from clinical trials led to a saving of 2.4 days (vs clomipramine) to 4.7 days (vs amitriptyline) (p < 0.05, respectively) of work loss per patient for a 8-week treatment period. PMID- 8351693 TI - [Quality of life and migraine. Validation of the QVM questionnaire in hospital consultation and in general medicine]. AB - The feasibility, the validity and reliability of the questionnaire "Qualite de Vie et Migraine" (QVM) were assessed during a study performed on 107 patients recruited either in neurological departments in hospitals (N = 58) or by G.P. (N = 49). The study was designed as a Test-Retest, the self-questionnaire being filled twice at an interval of one week. The filling-in time was an average 7 min in hospital and 11 min for G.P.'s patients. The missing values were quite rare, between 1% and 2%. The items were assessed "very interesting" or "interesting" by 94% of the patients, and "easy" or "fairly easy to understand" by 96%. The principal component analysis performed on the whole sample allowed the extraction of 4 meaningful factors which were in agreement with the pre-defined structure of the questionnaire QVM. The 1st axis was a factor of psychological repercussion, the 2nd axis was a factor of functional and somatic repercussion, the 3rd axis was a factor of social repercussion and the 4th one was a factor of disturbance generated by the treatment. The QVM questionnaire allowed the calculation of a global index of quality of life and indexes according to the multifactorial structure. The global index was significantly higher for the most severe patients recruited in hospital, which means that the repercussion of migraine on quality of life was greater than for G.P.'s patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351694 TI - [High dose intravenous immunoglobulins in therapeutic arsenal in autoimmune and systemic diseases]. AB - Immune globulin are extracted from plasma pooled from 1000 or more donors. Each lot should contain at least 90% of intact IgG. Intravenous immune globulin are recommended unequivocally for some diseases: acute autoimmune thrombocytopenic purpura of childhood, autoimmune erythroblastopenia, haemophilia with anti-VIII antibodies, Kawasaki's syndrome, and perhaps, Guillain-Barre syndrome. Nevertheless, this therapy has been reported to be beneficial for more than 35 diseases thought to be produced by immunopathology. Large amounts of immune globulin, such as 400 to 2000 mg/kg are proposed over a period of two to five days. The safety of this treatment, which may be introduced without any special structure, is a very interesting quality of the intravenous immune globulin therapy. However, comparative efficacy against reference therapy, surveillance for long-term positive and adverse effects and cost-effectiveness should be carried out. PMID- 8351695 TI - Teenage pregnancy and child health in the urban Sahel. AB - Longitudinal data for more than 20,000 live births in the cities of Bamako (Mali) and Bobo-Dioulasso (Burkina Faso) are used to study the effects of young maternal age (less than 18 years and 18-19) on birth weight, child health care and feeding behavior, and child mortality, after controlling for other socioeconomic and demographic factors. Teenage pregnancies are associated with significantly worse prenatal health care and vaccination behavior, lower birth weights, earlier weaning, and, especially during the second year of life, higher mortality. A proxy for mother's school enrollment at the time of pregnancy is strongly linked to worse prenatal health behavior and weakly associated with other poor behaviors and health outcomes. Overall, the results highlight the importance of behavioral factors relative to strictly biological factors for explaining child health differentials. PMID- 8351696 TI - Safe abortions in an illegal context: perceptions from service providers in Belgium. AB - Until April 1990 abortion was illegal in Belgium all circumstances. However, a small group of health professionals had long provided high-quality abortion services in outpatient facilities and in hospitals. This study is a qualitative analysis of perceptions among providers of safe abortion in Belgium before and after it was made legal there. The providers' personal, psychological, and ethical reactions to abortion are investigated, as well as their opinions on how their activities should be organized in order to minimize problems. Standardized questionnaires with closed and open questions were used; 143 questionnaires were completed. Emotional reactions were reported as being the most difficult aspects of practicing abortion. The experience of Belgian practitioners is of value for health professionals working in a legally restricted setting who are willing to assume some judicial risks to facilitate legal change while demonstrating the public health utility of low-cost, safe abortion. PMID- 8351697 TI - The influence of spouses over each other's contraceptive attitudes in Ghana. AB - To what extent do spouses influence each other's reproductive goals? This question was investigated in Ghana with particular reference to family planning attitudes. Two mechanisms were identified as plausible explanations for why an individual's characteristics may affect a partner's beliefs and behavior. Quantitative evidence from the Ghana Demographic and Health Survey and qualitative information from focus-group research in Ghana were used in the analysis. Results from both data sources show that spousal influence, rather than being mutual or reciprocal, is an exclusive right exercised only by the husband. The study attributed the limited impact of family planning programs in Ghana and most of sub-Saharan Africa to the continued neglect of men as equal targets of such programs. PMID- 8351698 TI - A community study of gynecological and related morbidities in rural Egypt. AB - This study assesses the prevalence of gynecological and related morbidity conditions in a rural Egyptian community. A medical examination was conducted on a sample of 509 ever-married, nonpregnant women. For gynecological morbidities, genital prolapse was diagnosed in 56 percent, reproductive tract infections in 52 percent, and abnormal cervical cell changes in 11 percent of the women. For related morbidities, anemia was present in 63 percent of the women, followed by obesity (43 percent), hypertension (18 percent), and urinary tract infection (14 percent). Regression analysis of risk factors demonstrated the contribution of social conditions and medical factors to these diseases. Reproductive tract infections were shown to occur more frequently with uterovaginal prolapse, IUD use, presence of husband (regular sexual activity), and unhygienic behavior. Genital prolapse increased with age and number of deliveries. Age, recent pregnancy, education, socioeconomic class, and workload showed significant associations with related morbidity conditions. This evidence challenges national health programs to go beyond safe motherhood, child survival, and family planning in its services to women, and to consider the social context of health as well. PMID- 8351699 TI - The simulated client method: evaluating client-provider interactions in family planning clinics. AB - The "simulated client" method was first detailed in the family planning literature in 1985, but it has not been extensively covered since. As used by the authors to study client-provider interactions in family planning programs, this method essentially consists of sending women to a family planning service provider to request information, and interviewing them after the encounter. The women do not reveal to service providers they are participating in the study. This report describes the method; reviews some of the theoretical, ethical, and methodological issues related to it; and underlines its usefulness as a tool for examining quality-of-care issues in family planning programs. PMID- 8351700 TI - The cost of IUD failure in China. PMID- 8351701 TI - Indonesia 1991: results from the Demographic and Health Survey. PMID- 8351702 TI - Timeline of immunosuppression. PMID- 8351703 TI - 5th Asian Cyclosporine (Sandimmun) Workshop. Proceedings. Taipei, Taiwan, Republic of China, April 21-23, 1993. PMID- 8351704 TI - Optimization and long-term evaluation of renal function in sandimmune-treated renal allograft recipients. PMID- 8351705 TI - Effect of cyclosporine on renal function in survivors of liver transplantation after 1 year. PMID- 8351706 TI - Renal transplantation in the cyclosporine era. PMID- 8351707 TI - Long-term safety of cyclosporine in renal transplant recipients: worldwide experience. PMID- 8351708 TI - Current status of kidney transplantation and immunosuppressive therapy in Japan. PMID- 8351709 TI - Immune risk factors: impact on the incidence and diagnosis of rejection. PMID- 8351710 TI - Immunologic parameters for the diagnosis of graft rejection. PMID- 8351711 TI - Hyperlipidemia and hypertension: impact of steroid withdrawal. PMID- 8351712 TI - Simultaneous kidney-pancreas transplantation at the University of Wisconsin. PMID- 8351713 TI - Xenotransplantation: state of the art. AB - Today, at the beginning of the xenogeneic era of transplantation, only simple and single observations about comparative physiology and biochemistry, and even anatomy, are known. Very few data exist which in addition inform about mechanisms after successful xenotransplantation. Nothing is known about phenomena following successfully suppressed hyperacute xenogeneic rejection. Neither the elimination of single factors nor the mitigation of whole systems have led to clinically relevant survival times. Pig organs transplanted into nonhuman primates survived a maximum of 22 days. The hope that transgenic manipulation and modification would be useful to prolong survival times of xenogeneic grafts still waits for evidence. But, within a short time, xenotransplantation could enable patients to receive a life-saving animal organ as an alternative to an allograft. Xenotransplantation would, as a new dimension in medicine, shorten if not eliminate waiting lists. Therefore, scientists must vigorously develop xenografting as a viable alternative for transplantation. PMID- 8351714 TI - Ethical aspects in xenotransplantation. AB - Ethics aims to achieve optimal human behavior. However, applied ethics depend on the cultural environment. In medicine, ethics could allow an amoral operation in a fetus or in chronically ill patients because it is new and rich in prospects for acquiring knowledge and could improve the quality of life of the patient or at least save the life. The operation itself must not be ill natured or unethical and the patient must not be misled or given false hope over the outcome. Ethics would allow us to offend the dignity of man, such as by xenotransplantation, because the wish for well being is often greater than the desire to retain dignity. Ethics in xenotransplantation must be based on the interests of the poor and unlucky patient and must aim for the good of everyone, but especially meet the patient's demands. PMID- 8351715 TI - Design of clinical development in transplantation. PMID- 8351716 TI - State of the art of liver transplantation in the USA. PMID- 8351717 TI - Surgical refinements in liver transplantation. PMID- 8351718 TI - Optimization of cyclosporine therapy. AB - Cyclosporine is a potent tool in the immunosuppressive armamentarium. It provides relatively selective inhibition of T-cell responses without dampening nonspecific resistance. However, its use is confounded by a pleiotropic array of side effects, the most important of which is renal dysfunction with the not uncommon sequelae of hypertension, hyperuricemia, and hyperkalemia. The hepatic injury associated with CyA administration, which is characterized by a chronic elevation of serum transaminase values, is potentiated by azathioprine or recrudescent or de novo viral infections. Finally, the proclivity of the drug to produce hyperlipidemia may jeopardize long-term survival; patients not infrequently require gemfibrizol and/or pravastatin therapy to control triglyceride and/or cholesterol levels, respectively. Two strategies appear to be useful. Our concentration-control strategy assesses CyA exposure by analyzing serial pharmacokinetic profiles, titering drug doses to achieve initial steady state concentrations of 400 ng/mL during continuous i.v. infusion, and to achieve average concentrations, namely AUC divided by dosing interval (in hours), of 550 ng/mL initially with trough levels of 200 ng/mL or above. Pretransplant pharmacokinetic profiling permits prediction of the appropriate initial i.v. dose in 73% of patients, and in combination with a posttransplant profile of the oral dose in about 60% of patients. The target oral concentrations are progressively reduced, thereby permitting prospective CyA control and minimizing adverse effects. The second synergistic drug strategy uses the median effect mathematical model to identify new drug combinations. The combination of CyA with RAPA, a macrolide which inhibits lymphokine signal transduction, and with BQR, a difluoro quinoline carboxylic acid analog that inhibits pyrimidine biosynthesis, permits at least a 20-fold reduction of the CyA dose in rat allograft models as well as prevents the activation of some CyA-resistant rejection pathways. Future investigations of pharmacologic strategies are undoubtedly likely to re-enforce the efficacy and safety of CyA administration for a range of immunologic disorders. PMID- 8351719 TI - Development of the living-related donor liver transplant program at the Texas Medical Center: initial results and surgical complications. PMID- 8351720 TI - Extracorporeal liver assist device (ELAD): a preliminary report. PMID- 8351721 TI - Prolonged administration of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) after T-cell-depleted allogeneic bone marrow transplantation. PMID- 8351722 TI - Bone marrow transplantation for pediatric patients with severe aplastic anemia in Taiwan. PMID- 8351723 TI - [Cutaneous manifestations of AIDS]. PMID- 8351724 TI - [Perimenopausal hemorrhage of uterine origin]. PMID- 8351726 TI - [Liver tumors manifested as hemorrhages: 9 case reports]. PMID- 8351725 TI - [Conservative treatment of cancer of the breast in Tunisia]. PMID- 8351727 TI - [Epidemiology of diabetic retinopathy]. PMID- 8351728 TI - [Endemic goiter: 39 particular case reports]. PMID- 8351730 TI - [Cutis marmorata telangiectatica congenita: 2 case reports]. PMID- 8351729 TI - [An anatomo-clinical and histogenetic study of Kaposi's sarcoma]. PMID- 8351731 TI - [Hydatidiform mole coexisting with a normal fetus: a rare case report and review of the literature]. PMID- 8351732 TI - [Effect of ethanol on carboxypeptidase H in the rat brain]. AB - It is established that under a single-dose introduction of ethanol activity of carboxypeptidase H increases. During chronic consumption of ethanol changes of enzyme activity was less than during a single-dose introduction of ethanol. Most considerable changes in carboxypeptidase H activity are observed in the pituitary gland, hypothalamus and striatum. Ethanol effect on the activity of membrane bound and soluble forms of enzyme was distinguished. It is supposed that carboxypeptidase H is involved into the formation of response to ethanol. PMID- 8351733 TI - [Effect of an electromagnetic field on subtilisin from Bacillus subtilis 316 m]. AB - The influence of electromagnetic field on the subtilisin of Bacillus subtilis strain 316 M preparation has been studied. It is the increase 30-60% of the proteolytic activity during 60-100 min treatment was observed. The effect of activation is stable for a month at +4 degrees C. The increase of the proteolytic activity is connected with conformational changes of the enzyme molecule, with the decrease of pI from 11.4 to 9.2 in particular. PMID- 8351734 TI - [Metabolism in experimental chronic ischemic heart disease]. AB - An increase in frequency of heart contractions, changes in the bioelectrical heart activity and decrease of the force-pump heart function are observed in the rabbits with model chronic ischemic heart disease lipid metabolism in significantly changed the concentration of cholesterol in the right ventricle myocardium as well as the concentrations of unsaturated lipid acids in the heart tissues increase, while the content of saturated lipid acids and antioxidant activity of plasma decrease. Bioenergetic processes change as follows: succinate dehydrogenase and alpha-keto-glutarate-dehydrogenase activity decrease, while the concentrations of glycogen, lactic and pyruvic acids and lactate dehydrogenase activity in the heart tissues increase. PMID- 8351735 TI - [Optimal conditions for the functioning of a urease-based biosensor and pH sensitive field transistors. Determination of urea in solution]. AB - The article deals with the optimal conditions of urea determination in solution by the enzyme sensor based on pH-sensitive field effect transistor. The dependence of response level on temperature, pH, ionic strength, buffer capacity were investigated. 10 mM phosphate buffer, pH 7.4 containing 200 mM NaCl is optimal for possible measurements of urea in diluted blood. Temperature change in the measured samples from 15 degrees to 30 degrees C does not affect the sensor signal value. Stability of immobilized ureas was investigated at storage under different conditions. In the presence of 1 mM EDTA activity of immobilized enzyme does not change during one month storage at 4 degrees C. PMID- 8351736 TI - [Effect of fluoroaluminate on the passive transport of calcium in the plasma membrane fraction of the pig myometrium]. AB - Study of the effect of aluminium, fluoride-ions and fluoroaluminium on the passive transport of Ca2+ through the plasma membrane of the myometrium cells has shown that 10 microM of Al3+, 1 mM of F- and the both ions taken in the mentioned concentrations do not affect this process. At the same time 10 mM of F- as well as 10 microM of Al3+ together with 10 mM of F- inhibit a passive output of calcium from vesicles. The results obtained suppose that inhibitory regulation of the passive transport of calcium in the myometrium sarcolemma is executed through Gi-protein. PMID- 8351737 TI - [Cartilage collagen in health and in pathology]. AB - The paper deals with the latest data on structure organization of collagen proteins--basic and minor components of the extracellular matrix of the animal cartilage tissue. Their genetic determination and tissue specificity, differences in the initial structure, sizes of spiral and globular domains, availability of - SH- and --S--S-bonds are emphasized. Data are presented which confirm that the change in the collagen state is one of the determining factors in pathogenesis of the cartilage tissue. PMID- 8351738 TI - [Expression and function of x-mla genes associated with leukemic transformation of cells]. AB - Expression of genes, associated with leukemic transformation and called x-mla, was studied in cells of various types of experimental leukemia and in homologous normal cells. Augmentation of x-mla expression in malignant haemopoietic cells and lack or very low expression in normal tissues and non-haemopoietic tumors of mice and rats has been revealed. The involving of x-mla in proliferation control of leukemic but not normal cells has been shown. Product of x-mla--p46 was synthesized in cell-free translational system and purified. Its amino acid composition was determined and its mitogenic, RNAase activities, and ability to phosphorylation have been investigated. PMID- 8351739 TI - [Properties of basic (splitting off arginine and lysine residues) carboxypeptidases and their role in the functioning of biologically active peptides]. AB - Properties of carboxypeptidases that cleaved arginine and lysine from C-terminus of peptides are considered. Their role in processing, modulation and inactivation of active peptides are discussed. Mechanisms of regulation of carboxypeptidase H activity are considered. PMID- 8351740 TI - [Purification and properties of lectins of Polygonatum multiflorum [L.] All. and Polygonatum verticillatum [L.] All]. AB - The lectins from rootstocks of Polygonatum multiflorum [L.]. All. and P. verticillatum [L.] All. were purified by affinity chromatography on thyroglobulin sepharose. Purified lectins were obtained from fresh raw material of P. multiflorum and P. verticillatum, 340 mg/kg and 120 mg/kg, respectively. The both lectins do not contain carbohydrates. Amino acid analysis has shown that the both lectins had high content of asparaginic acid/the lectin from P. verticillatum almost 28%. Ion-exchange chromatography permitted separating the lectin from P. multiflorum into 8 isoforms, that did not differ in molecular weight. Purified lectins interacted with sialic acid and did not interact with other monosaccharides. Purified lectins agglutinated rabbit and rat erythrocytes best of all, they less agglutinated mice and horse erythrocytes, but did not agglutinate human, cow, sheep and frog erythrocytes at all. Lyophylized lectins are amorphous white powders, that are well soluble in distilled water. Scientific production co-operative "Lectinotest" began serial production of lectin from Polygonatum multiflorum from 1992 year. PMID- 8351741 TI - [Effect of the hypothalamo-hypophyseal-adrenocortical system on the functional state of Hageman-dependent systems of blood after immobilization stress]. AB - The reaction of haemostatic system under the condition of sympathetic receptions blocking and the suppression of the hypothalamic-hypophyseal-adrenocortical system reactivity as the result of immobilisation stress have been studied in the experiments on rabbits. It was found that the sympathetic nervous system and HHAS took part in the regulation of the blood coagulation, fibrinolysis and kininogenesis under stress-syndrome development by the activation of lysosomal apparatus of neutrophilic leukocytes of peripheral blood. PMID- 8351742 TI - [Isolation, purification and various properties of aspartate kinase from the cyanobacterium Plectonema boryanum]. AB - The enzymic activity of aspartate kinase from filamentous cyanobacteria Plectonema boryanum at the logarithmic phase of growth has been studied. Aspartate kinase was purified eleven times and extracted in functionally homogeneous state from the cell-free extract by the methods of ammonium sulphate salting-out, ion-exchange chromatography and isoelectric focusing. Some physical and chemical characteristics of the enzyme have been studied: pI-7.2; optimum pH 9.0; optimum temperature-55 degrees C. The dependence of enzymatic reaction on concentration of substrates, co-enzymes, cofactors and protein has been established. Regulation of aspartate kinase activity by amino acids of the aspartate family has been investigated. L-threonine, L-homoserine and L isoleucine (0.01-0.001 M) have a pronounced inhibitory effect. L-lysine and L methionine are not immediate inhibitors of aspartate kinase but intensify the inhibitory effect of threonine by the cumulative mechanism. PMID- 8351743 TI - [Tissue metabolism in ruminants as affected by ionophores]. AB - Remarkably influencing the VFA formation processes and their ratio in the rumen, ionophore action involves the range of free amino acids and individual enzymatic reactions of subcellular fractions of the rumen mucosa, heart muscle and longissimus muscle, kidneys and liver. The discovered reverse relationship between changes of levels of aminoacylation of tRNA and the amount of the respective free amino acids possibly is one of the crucial links in the common regulatory mechanism aimed at the maintenance of the specific stability of tissue and organ metabolism (including protein biosynthesis) in ruminants. It seems to be responsible for different effects of the ionophore on the investigated processes in different tissues and organs. PMID- 8351744 TI - [Sensitivity of chlorpromazine-modified eryhtrocytes to cold stress]. AB - Development peculiarities of hypertonic cold shock of erythrocytes modified with chlorpromazine were studied, maximum protection effect under cooling of cells is registered when using chlorpromazine in the concentration 7 x 10(-5) M. Spectrin denaturation does not change general pattern of the effect of different concentrations of amphipat on sensitivity of erythrocytes to the cold shock but it sensitizes cells modified by chlorpromazine (7 x 10(-5) M) to the further cooling. Differences between native cells and erythrocytes with denatured spectrin are levelled at higher concentrations of amphypat, certain protective effect being observed at certain values of the medium tonicity. PMID- 8351745 TI - [Effect of ionizing radiation on the structure of erythrocyte membranes]. AB - Effect of electrons with the energy 5MeV on the erythrocyte ghosts structure has been investigated using fluorescent probes 1.8-ANS and DSP-12. The number of ANS binding sites was shown to decrease as affected by irradiation. It was found that radiation caused reduction of the erythrocyte membrane surface area. PMID- 8351746 TI - [Lipid peroxidation in sarcoplasmic reticulum membranes from rock perch and rabbit muscles]. AB - Nonenzymic lipid peroxidation in the membrane of the fragmented sarcoplasmic reticulum from white dorsal muscle of teleost fish Scorpaena was studied. It was shown that the concentrations of ferrous ions 15 microM and ascorbic acid 0.3 mM were sufficient for lipid peroxidation activation. Ethanol inhibited lipid peroxidation of the fragmented sarcoplasmic reticulum membranes from white muscle of Scorpaena and rabbit. PMID- 8351747 TI - [Cu(2+) complexes as inhibitors of free radical oxidation of lipids]. AB - Cu(2+) complexes of chelate ligands have been studied for their effect on oxidation of rat blood plasma lipids, sphingomyelin, lecithin by the method of chemoluminescence. The studied Cu(2+) complexes have been shown to possess pro oxidant and antioxidant properties depending on their concentration. Antioxidant activity of alpha-tocopherol, ionol (2,6-di(tert)-butyl-4-methylphenol) and Cu(2+) complexes by the lipid oxidation has been compared. PMID- 8351748 TI - [Effect of regulatory light chains of myosin on aggregation of its subfragment 1]. AB - Chymotryptic (Ch-Cl) and Mg(2+)-papain subfragments 1 of (Mg-Cl) skeletal myosin has been studied. Mg-Cl is known to differ from Ch-Cl by the presence of the regulatory light chain (RLC) and elongated heavy chain including C-end hinge segment. Experimental data prove the decisive part of coordination bondings with bivalent cations in stabilization of RLV on myosin head hinge segment. Hydrophobic interactions are also significant that is evidenced by the intensive aggregation between subfragment Mg-Cl molecules, after RLC dissociation. PMID- 8351749 TI - [Thrombolytic effect of plasmin, miniplasmin and fibrinolysin in simulated intraocular hemorrhage]. AB - The fibrinolytic properties of the preparations of plasmin (Pm), mixture of plasminogen and streptokinase (Pg+Sk), miniplasmin (m-Pm) and fibrinolysin have been investigated on the models of rabbit's hyphema. The action of preparations of Pm and Pg+Sk had approximately equal therapeutic index--the total destruction of clots proceeded for 12.0 days, that was 6.6 days less than in the control group. The therapeutic effect for m-Pm was 3.6 days. The dose of preparation of m Pm, necessary for total destruction of clots, was 15-20% greater than for the same dose of Pg+Sk. The preparation of fibrinolysin, used in the same quantities of proteolytic activity, as Pg and m-Pg, (16 caseinolytic units per 1 injection) had no therapeutic effect. PMID- 8351751 TI - Metastasis of renal cell carcinoma to the contralateral renal pelvis. AB - Extremely rarely renal cell carcinoma metastasizes to the contralateral renal pelvis or ureter. The present report concerns a case where a metastatic tumor could be successfully removed from the left renal pelvis 3 years after right nephrectomy for the primary tumor. A review of the literature revealed this to be only the fourth such case documented. PMID- 8351750 TI - [Inactivation of glutathione reductase by quinones and nitrosocarbamides]. AB - Quinones inactivate oxidized glutathione reductase (EC 1.6.4.2) from yeast with rate constants (ki) ranging from 0.03 M-1s-1 (p-benzoquinone) to 10(3) M-1s-1 (bromanyl). It is glutathione, but not NADP+ that protects the enzyme from inactivation, which shows that quinones interact with a glutathione-binding centre, cysteine-2, most probably. The mechanism of inactivation by quinones differs from that by nitrosoureas which inactivate only the reduced enzyme, modifying the reduced catalytic disulphide. 1,3-bis-(2-chloroethyl)-1-nitrosourea acts as the most rapid inactivator of the enzyme, possessing ki of 0.77 M-1s-1. PMID- 8351752 TI - Two cases of urothelial tumor with high serum level of carcinoembryonic antigen and TA-4. AB - Two rare cases of urothelial tumor with high serum carcinoembryonic antigen (CEA) and TA-4 levels are presented. One is a case of lymph node metastasis due to bladder tumor: pathological diagnosis revealed mucoepidermoid carcinoma. The other is a case of left renal pelvic tumor: pathological diagnosis revealed transitional cell carcinoma with glandular and squamous differentiation. The serum CEA and TA-4 levels, high before surgery, decreased after surgery. PMID- 8351753 TI - Schwannoma of the penis. AB - A schwannoma located in the penile shaft in a 74-year-old patient is described. A review of the schwannoma of the penis is presented and the importance of the S 100 protein stain is stressed. PMID- 8351755 TI - Platinum accumulation in the kidney and changes in creatinine clearance following chemotherapy with cisplatin in humans. AB - To evaluate the effects of repeated administration of cisplatin on kidney platinum (Pt) accumulation and renal function, Pt content in the kidney was determined in 31 autopsy cases and changes in creatinine clearance (CCr) were retrospectively assessed in 26 of 31 autopsy cases. There was no significant correlation between the cumulative dose of cisplatin and Pt content in the kidney. However, the kidney Pt level was correlated with the dose of cisplatin injected within a 7-month period prior to the patient's death. We suggest that the dose of cisplatin injected during a relatively short period before a patient's death affects Pt content in the kidney. Neither the total dose of cisplatin nor the Pt content in the kidney was significantly correlated with the decrease in CCr following chemotherapy with cisplatin. PMID- 8351754 TI - Continuous evaluation for retroperitoneal hematoma following extracorporeal shock wave lithotripsy. AB - In this paper we report on a patient with extensive retroperitoneal hematoma due to extracorporeal shock wave lithotripsy (ESWL) for a renal stone. The patient had a negative history of previous primary renal disease or risk factors for retroperitoneal hemorrhage after ESWL. The hematoma was treated conservatively and it was completely absorbed 9 months after ESWL as evaluated by computed tomography. Gd-DTPA-enhanced dynamic magnetic resonance imaging (dynamic MRI) was performed immediately after formation of the hematoma. The decrease in renal blood flow in the affected kidney could be observed in this patient by dynamic MRI and its time intensity curve. PMID- 8351756 TI - Mean nuclear volume of bladder cancer: stereological estimation and its clinical value. AB - Mean nuclear volumes (MNVs) of bladder cancer cells from the specimens of 100 patients were estimated by stereological procedure. The value of MNVs of bladder cancer were ranged widely, from 114.6 to 1,041.9 microns3. However, strong correlation was observed between MNV and histopathological grade and stage. Furthermore, the MNV predicts the biological behavior including the malignant potential and prognosis of the patient. Patients with MNV below 315 microns3 had significantly better prognosis than those with MNV above this value (p < 0.01). The 5- and 10-year survival rates for patients with MNV below 315 micron3 were both 97%, while those for patients with MNV above 315 microns3 were 65 and 58%, respectively. MNVs of the recurrent tumors were significantly increased, compared with those of the initial tumors (p < 0.01). MNV of extirpated tumor specimens following chemotherapy consisting of cisplatin and Adriamycin through balloon occluded arterial infusion (BOAI) was significantly decreased, compared with that before BOAI (p < 0.01). We conclude that the MNV is an excellent predictor for the prognosis of the patient and the tumor recurrence. Furthermore, the stereological estimation of nuclear volume is a simple, quick, inexpensive, and reliable method to assess quantitative analysis of the histological and biological character of bladder cancer. PMID- 8351757 TI - Use of maintenance intravesical bacillus Calmette-Guerin (BCG), with or without intradermal BCG, in patients with recurrent superficial bladder cancer. Long-term follow-up of a randomized phase 2 study. AB - To study maintenance Bacillus Calmette-Guerin (BCG) therapy we treated 49 patients with recurrent superficial bladder cancer pTa and/or carcinoma in situ, failing previous intravesical chemotherapy. They received 20 intravesical instillations in 1 year, with or without 6 intradermal inoculations. Side effects were frequent, causing treatment stop in 14 patients (29%). Drug-induced cystitis was the most frequent side effect, seen in 29 patients (59%). Forty-two patients were evaluable for response. During the first 2 years of the study 14 patients (33%) had one (n = 8) or more (n = 6) recurrences. A total of 18 patients (43%) remained recurrence free with a median follow-up of 47 months. Progression was seen in 2 patients from pTa to pT1, another patient died of metastatic bladder cancer after 47 months. PPD skin test conversion was of no prognostic value. The use of intradermal inoculations caused no significant increase of toxicity and had no effect on efficacy, however, both groups were small. It caused no local side effects. We conclude that maintenance BCG therapy can be useful for patients with recurrent superficial bladder cancer failing previous intravesical chemotherapy. PMID- 8351759 TI - Post-natal management of antenatally detected, bilateral hydronephrosis. AB - 26 children, with antenatally detected, isolated, bilateral hydronephrosis (thus consistent with pelvi-ureteric junction obstruction), were investigated for up to 7 years. The aim was to avoid operation. 34 kidneys were never operated on. Despite initially often severe hydronephrosis and poor isotope wash-out on the renogram, half of the kidneys improved or even normalized during follow-up. The final glomerular filtration rate (GFR) was always normal or almost normal. 18 kidneys came to surgery, because of poor filtration, symptoms or social reasons. At the end of the follow-up, GFR was normal in all but 2 kidneys. In a subgroup of the kidneys, with initially severe reduction in filtration, half were operated on and half were not; at the end, the GFR was normal in all of the non-operated kidneys (and in all but 1 of the operated kidneys). Total GFR was at the end normal or almost normal also in the children with persistingly filtration-reduced kidneys (always unilaterally), because of compensation by the contralateral, although hydronephrotic kidney. Thus, in this study the renographic parameters were not very helpful in predicting the prognosis. There was no consistent difference between operative and non-operative treatments on final filtration. Also hydronephrotic kidneys possessed a substantial capacity for contralateral compensation. It is concluded that the initial approach to bilateral, antenatally diagnosed hydronephrosis may safely be non-operative. This allows time for the clear expression of sustained impairment of renal filtration requiring surgical intervention. PMID- 8351758 TI - Single-dose versus 3-day prophylaxis with ciprofloxacin in transurethral surgery. A clinical trial. AB - In 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5 failures and in the 3-day prophylaxis group there were 6 failures. The difference is not significant. In 17 patients whose urine culture preoperatively yielded microorganisms the 3-day prophylaxis significantly eradicated the bacteriuria in 83% of the patients. PMID- 8351760 TI - Promotion of metastases by tumor necrosis factor in rats bearing Dunning R3327 MAT-LyLu prostatic cancer. AB - We examined the effects of recombinant human tumor necrosis factor (rTNF) on highly metastatic rat prostatic cancer, Dunning R3327 MAT-LyLu, in vivo. It seemed that the inhibition of tumor growth needed more than 5 x 10(5) units of rTNF and this dose was near the lethal dose. Concerning the effect of rTNF on metastasis, we found that the metastasis to lung was promoted by 1 x 10(5) units of rTNF and the promotion of metastasis was restricted by indomethacin. Although MAT-LyLu cells were producing a significant amount of prostaglandin E2, rTNF did not enhance the production. We therefore consider that the promotion of metastasis was not mediated by prostaglandin E2 from MAT-LyLu cells but was mediated by other very complicated conditions. Further studies are necessary to resolve the mechanisms. PMID- 8351761 TI - Changes of rat urinary bladder during acute phase of spinal cord injury. AB - Spinal cord injury (SCI) at Th13 was induced in female Wistar rats, and changes in the urinary bladder were examined during the acute phase of SCI. Wet weights of the spinal bladders increased twofold over controls by 7 days after SCI. Intravesical volumes increased sixfold over control values by day 3, and then decreased 7 days after the injury. Maximal pressure within the bladder decreased in all spinal rats compared with controls. Smooth muscle cells were isolated from the urinary bladder, and their total protein and DNA content were measured by multiparametric cytofluorometry. DNA content of isolated smooth muscle cells decreased by day 3 and remained 7 days after the spinal injury. Total protein content of isolated smooth muscle cells was decreased 1 day after and increased 7 days after the spinal injury, just when spinal reflex of the bladder recovered. These findings suggest that hypertrophy of smooth muscle cells in urinary bladder is related to the activity of peripheral autonomic nerve and that smooth muscle cells already begin to hypertrophy during the spinal shock period to adjust themselves to the new state, that is, the spinal bladder. PMID- 8351762 TI - A case of weak mineralocorticoid-producing benign adrenal tumor. AB - Tumors producing weak mineralocorticoids are exceedingly rare and most of them predominantly produce 11-deoxycorticosterone. We present a case of adrenocortical adenoma in which the overproduction of 18-hydroxydeoxycorticosterone exceeded that of 11-deoxycorticosterone. PMID- 8351763 TI - Renal cell carcinoma insulated in the renal capsule with calcification and ossification. AB - We describe a case of renal-cell carcinoma insulated and entrapped in the renal capsule by a calcified and ossified rim. To our knowledge, this is the first time a renal-cell carcinoma of the renal capsule is reported. The fact that the tumor cells originated from the distal/medullary tubules was supported by immunohistochemical studies. The pertinent literature is reviewed. PMID- 8351764 TI - Spinal cord injury. An overview. AB - Advancements in the management of urologic complications such as the neurogenic bladder have been essential to improving the quality of life and longevity of patients with spinal cord injury. These advances are discussed in greater detail in the subsequent articles in this issue. Despite the many improvements that have been made in post-trauma care, spinal cord injury remains a devastating lesion of the nervous system. Current therapies have not proved to be particularly effective in preventing or reversing damage to the spinal cord. Still, every effort should be made to preserve remaining function and to prevent complications. The care of these patients has been significantly improved with the development of specialized multidisciplinary centers. The emphasis in current treatment focuses on rehabilitation and adaptation to the disability and on prevention of secondary disabilities. Research in basic and clinical neuroscience will result in better, more useful care and treatment for those with spinal cord injury. However, even then, a neurorehabilitation team will be essential to care for these patients. Continuing efforts must be made to ensure that people with spinal cord injury lead full and productive lives. PMID- 8351765 TI - Anatomy and physiology of the lower urinary tract. AB - The lower urinary tract has two main functions: storage and periodic elimination of urine. These functions are regulated by a complex neural control system located in the brain and spinal cord. This control system performs like a simple switching circuit to maintain a reciprocal relation between the reservoir (bladder) and outlet (urethra and urethral sphincter) components of the urinary tract. Spinal cord injury disrupts voluntary control and the normal reflex pathways that coordinate bladder and sphincter function. Studies in animals indicate that recovery of bladder function after spinal injury is dependent on the reorganization of reflex pathways in both the peripheral and the central nervous system. Part of this reorganization may be influenced by neural-target organ interactions that are mediated by neurotrophic factors released by the peripheral organs. PMID- 8351766 TI - Acute urologic management of the patient with spinal cord injury. Initial hospitalization. AB - The early urologic management of the patient with spinal cord injury can be straight-forward. Intermittent catheterization is the most acceptable therapy until final urologic decisions have been made based on appropriate urodynamic studies. The intermittent catheterization should be aggressive and periodic to empty the bladder, and the patients should be encouraged to do this independently when they are able to. Should any changes occur during this management, such as fever, infection, or dysreflexia, urodynamic studies should be done to identify high-pressure voiding with a high (40-60 cm H2O) leak-point pressure. Then, appropriate therapy should be instituted to lower the bladder pressure, including, initially, anticholinergic drugs and, ultimately, maybe another method such as a sphincterotomy. We usually reserve aggressive invasive therapy for patients whose spinal cord injury has totally evolved and who are rehabilitating, usually no less than 6 months after spinal cord injury, except in severe cases. There is controversy about the initial and long-term treatment of patients with intermittent catheterization, antibiotics, or both. This controversy will continue. Upper urinary tract complications associated with spinal cord injury have been virtually eliminated with better urologic therapy, and the incidence should continue to be negligible if proper therapy is given. Patients who have maintained good bladder management and who are doing well physically with good nutritional habits and medical care since their spinal cord injury will have a much better outcome than those who have more severe urologic and medical problems. PMID- 8351767 TI - Acute neurologic management of the patient with spinal cord injury. AB - Early and effective spinal immobilization, physiological support, precise radiographic analysis, and surgical intervention tailored to the specific anatomic pathology form the basis for appropriate management of spinal injury. Despite improvements in each of these areas, however, the neurologic outcome in patients with severe deficits remains problematic. Research into the prevention of adverse metabolic changes that occur in the acutely injured spinal cord may offer hope for improved outcomes. PMID- 8351768 TI - Long-term urologic management of the patient with spinal cord injury. AB - The primary goal of bladder management in the patient with a spinal cord injury is to achieve adequate bladder drainage, low-pressure urine storage, and low pressure voiding. This will help prevent urinary tract infections, bladder wall damage, bladder overdistention, vesicoureteral reflux, and stone disease. Bladder retraining is indicated in all patients with disorders of the spinal cord and the brain. The basic aim is to provide bladder drainage without indwelling catheters and, if possible, without leg bags. Bladder retraining is usually begun with intermittent catheterization, with the use of alpha blockers to improve drainage in patients who are wearing leg bags or with anticholinergic drugs to improve continence. However, bladder retraining may be contraindicated in patients with vesicoureteral reflux or stone disease and in patients with impending renal failure. It is therefore important to evaluate all patients with neurogenic bladder using urodynamics, nuclear scanning, renal ultrasound, and voiding cystourethrography. In patients with stone disease, intravenous urography may also be required. Understanding of the basic neurologic lesion and bladder dysfunction is therefore vital to bladder retraining or transurethral surgery to provide adequate voiding. The regular periodic follow-up of all patients is vital to protect renal function. PMID- 8351769 TI - Management of urinary stones in the patient with spinal cord injury. AB - The main objective of the urologist treating patients with spinal cord injury is to preserve renal function. In order to minimize morbidity, all attempts must be made to maintain a low bladder pressure, sterile urine, and a non-obstructed drainage system. These patients remain at increased risk of infection and stone formation despite all clinical intervention. Diligence in routine follow-up and careful evaluations will provide the best possible results. In the face of urolithiasis, ESWL, percutaneous nephrolithotomy, and chemolysis are effective means of treatment with acceptable morbidity. With future technologic advancements and implementation of neurostimulators to improve the urodynamic profiles, the incidence of renal insufficiency, urolithiasis, and overall morbidity in patients with spinal cord injury is likely to decrease. PMID- 8351770 TI - Antimicrobial agents in urinary tract infections in patients with spinal cord injury. AB - Because of the rapid introduction and active marketing of newer antimicrobial agents for urinary tract infections, it is important to evaluate newer antibiotics critically. Critical evaluation should be based on published reports, spectrum of action, and, very importantly, cost. Newer agents should be compared with known effective agents on the basis of hospital antimicrobial sensitivity tests. Simple, uncomplicated urinary tract infections caused by community acquired multiple drug-sensitive uropathogens can be treated with almost any currently available antimicrobial agent. In these situations, a low-morbidity, low-cost agent with limited dosage should be chosen. In general, a 3-day course of trimethoprim-sulfamethoxazole, nitrofurantoin, a first-generation cephalosporin, a penicillin agent, or in some cases a fluoroquinolone will be both medically and cost effective. For complicated urinary tract infections, more selectivity must be exercised in choosing an appropriate antibacterial agent. In these situations, it is necessary to initiate appropriate diagnostic studies to identify causes and to treat those complications appropriately. The choice of antibiotics must be based on culture results. Initial empiric treatment should be carried out with a broad-spectrum agent of low morbidity. In these complicated infections, fluoroquinolones may be effective with low expected morbidity. PMID- 8351771 TI - Urologic complications of spinal cord injury. AB - Spinal cord injuries in the past were associated with a very high mortality, predominantly from urologic complications and sepsis. Improvements in the urologic and medical management of these patients have significantly decreased the morbidity and mortality. Many complications may still develop during the urologic management, however. Periodic follow-up is thus essential to recognize and treat urologic complications in order to preserve renal function. PMID- 8351772 TI - Urinary diversion and reconstruction in the patient with spinal cord injury. AB - This article discusses surgical procedures that may be useful in the management of patients with spinal cord injury and is intended to be of practical use to those in general practice. In addition to a discussion of the pros and cons of indwelling Foley and suprapubic catheters, useful reconstructive and diversionary procedures are reviewed. PMID- 8351773 TI - Urologic management of spinal cord injury in children. AB - This overview of the management of children with spinal cord injury has focused on a program based on bladder dynamics. The bladder is modulated pharmacologically and surgically, if necessary, to create a reservoir that stores urine at low pressure, and emptying is achieved by clean intermittent catheterization. The parent assumes the responsibility for bladder emptying when the child is unable to perform catheterization. Reflex voiding in a balanced fashion is not advocated. The program described not only avoids the deleterious effects of high voiding pressures, it also obviates the wearing of a urinary collection device, which is impractical for most prepubertal boys, and it provides for emptying at predictable intervals in order to make the child more socially acceptable. This approach seems to improve the child's self-image, and it should increase the chances of useful participation in society and a fulfilling life. PMID- 8351774 TI - Urologic consequences of myelodysplasia and other congenital abnormalities of the spinal cord. AB - Spina bifida and other congenital abnormalities of the spinal cord are relatively common (1 per 1000 births). Early urologic evaluation to determine the extent of neurologic involvement of the lower urinary tract is essential. Urodynamic studies are important in determining voiding pressure and leak pressure and in classifying the type of detrusor and sphincter dysfunction. Therapy is directed toward preservation of the upper tracts. Many nonsurgical (clean intermittent catheterization and anticholinergic drugs) and surgical procedures allow the child to be continent and maintain a normal upper urinary tract. The importance of follow-up is stressed because neurourologic changes frequently occur, and prompt treatment or change of therapy is essential. Today, children with spina bifida are leading healthy, productive lives. A continued multidisciplinary approach to their care is important. PMID- 8351776 TI - Management of the neurogenic bowel in patients with spinal cord injury. AB - Bowel dysfunction in patients with spinal cord injury has a significant impact on quality of life as well as causing morbidity and death. This article reviews the pathophysiologic features of the neurogenic bowel of patients with spinal cord injury. Also discussed are the clinical manifestations, current options for management, and newer approaches that address this chronic and debilitating problem. PMID- 8351775 TI - Electrical stimulation of sacral roots for micturition after spinal cord injury. AB - In patients with suprasacral spinal cord injury, electrical stimulation of the sacral anterior nerve roots can produce micturition with low residual volumes of urine and reduced urinary tract infection. Voiding pressures can be maintained at acceptable levels by selective peripheral neurotomy and myotomy or, more commonly, by an intermittent pattern of stimulation. Occasionally, external sphincterotomy is required. The procedure is usually combined with division of the sacral posterior roots, which increases bladder capacity and continence; this also increases bladder compliance, which may be protective for the upper urinary tracts. A reduction in constipation usually is observed, and some patients are able to defecate with the aid of electrical stimulation. Penile erection is produced in a substantial proportion of male patients. The procedure has now been applied in about 700 patients with spinal cord injury, some of whom have been followed for nearly 15 years. The nerves do not appear to be damaged by long-term stimulation, and technical faults with the equipment are now uncommon. PMID- 8351777 TI - Clinical approach to the sexuality of patients with spinal cord injury. AB - This article discusses four complex clinical perspectives on the sexual impact of spinal cord injury: the sexual equilibrium between two people, the sexual psychology of one individual, the general biology of the organically impaired person, and the sexual pathophysiology of the spinal cord deficit. These topics affect the re-establishment and maintenance of a sexual life after irreversible spinal cord trauma. PMID- 8351778 TI - Sexual dysfunction after spinal cord injury. AB - Treatment of sexual dysfunction is an integral part of the rehabilitation of the patient with spinal cord injury. The degree of sexual dysfunction varies with the level and completeness of injury. A multidisciplinary approach is necessary to evaluate and treat these patients. Intracorporeal injections of vasoactive medications or vacuum devices are effective means of restoring erections in selected patients with spinal cord injury. Penile prostheses are rarely indicated for this purpose. PMID- 8351779 TI - Fertility options and success after spinal cord injury. AB - Over the past 9 years, the fertility potential for men with spinal cord injury and other neurological impairments has improved. Approximately 80% of men with spinal cord injury have semen (collected either by vibration or by electroejaculation using rectal probe) of sufficient quality to use in intrauterine insemination or in vitro fertilization. Assuming that other factors are equal, it would seem that length or level of injury are not dominating factors that control the quality of semen from these men. PMID- 8351780 TI - Sigma-rectum pouch (Mainz pouch II). AB - A substantial modification of the classic technique of ureterosigmoidostomy is introduced in this article. To date, this procedure has been used in 47 patients. This article reviews the surgical technique of the antemesenterial splitting of the intestine at the recto-sigmoid junction which creates a pouch by subsequent side-to-side anastomosis. PMID- 8351781 TI - Observations on the commercial production of ostrich (Struthio camelus) in the United Kingdom: rearing of chicks. AB - Two sets of ostrich eggs (60 and 120 eggs) were imported into the United Kingdom under class 1 quarantine restrictions. The eggs were incubated and observations were made on the growth, survival and sex ratio of the chicks hatched. The chicks decreased in weight for five days after hatching before they began a sustained period of exponential growth. They reached a liveweight of 4 kg five weeks after hatching. Female chicks grew significantly faster than male chicks. The survival rates of the chicks to three months of age were 66.7 per cent and 78.3 per cent, respectively, for the two sets of eggs, and mortality restricted mainly to the first four weeks of rearing. All the birds which died showed poor rates of growth before they died. The sex ratio of both groups was skewed 2:1 towards males. PMID- 8351782 TI - Morbillivirus antibodies of maternal origin in harbour seal pups. (Phoca vitulina). PMID- 8351783 TI - Detection of bacterial sinusitis in the Mongolian gerbil (Meriones unguiculatus) using magnetic resonance imaging. PMID- 8351785 TI - Control of foot-and-mouth disease. PMID- 8351784 TI - Ovine ophthalmitis associated with Listeria monocytogenes. PMID- 8351786 TI - Disease similar to swine fever. PMID- 8351787 TI - Solar haemorrhages in dairy cattle. PMID- 8351788 TI - Retina, brain and blood cholinesterase levels in cats treated with oral dichlorvos. AB - Dichlorvos (DDVP) is used as an antihelmetic, principally in dogs, cats, pigs and horses. Retina, whole blood, erythrocyte, plasma and brain cholinesterase (ChE) activities were monitored following DDVP exposure in cats to establish their use as indicators of exposure to a ChE inhibitor. Following DDVP exposure, whole blood ChE activity was 16.8% of preexposure, erythrocyte ChE activity was 33% of preexposure, and plasma ChE was 19% of preexposure values. Brain and retinal ChE activities were reduced to 45% and 43% of control values. Retinal ChE paralleled brain activity. PMID- 8351789 TI - Field test of the new fungal identification system in POISINDEX. AB - A new program, Fungal Identification System (FIS) was introduced in POISINDEX (PI) in 1991. We studied the accuracy of this program compared to the traditional method of consulting an expert mycologist and also the utility of FIS for the certified specialist in poison information (CSPI) and the emergency department personnel. Fifteen samples were obtained from a Chicago area forest preserve and immediately identified by a CSPI using FIS from PI of summer-fall 1991. The samples were then refrigerated overnight and identified the following morning by a PhD mycologist, using standard mycological identification techniques (SMIT). Another group of 18 mushrooms were collected in August 1992 from rural southwestern Michigan and identified by FIS and SMIT after refrigeration overnight. In 4 cases the mycologist used both SMIT and FIS to identify the mushrooms. Identification by FIS did not match SMIT in 27 of 31 samples (1 was discarded and 1 was identified by FIS but not identified by SMIT). In 2 of 4 cases where the mycologist used FIS, a different answer was obtained from that obtained by the CSPI; however, these were still incorrect identifications. Four types of problems using FIS have been identified which can lead to erroneous results; these are the use of multipart questions, emphasis on color over less variable characteristics, questions which do not account for variability in morphology, and problems which arise from the sequence of questions. These points need to be addressed before FIS can be used as a safe basis for clinical recommendations. PMID- 8351790 TI - Isolation, purification, toxicity and some physicochemical properties of mycotoxins produced by aspergillus quadrilineatus isolated from acha (Digitaria exilis stapf) in Plateau State of Nigeria. AB - Some physico-chemical and toxicological studies were carried out on mycotoxins elaborated by Aspergillus quadrilineatus isolated from a grain foodstuff, acha (Digitaria exilis) in the Plateau State of Nigeria. The mycotoxins produced by A quadrilineatus were extractable from rice culture by chloroform. Column chromatographic separations of the crude extract in silica gel using different elution solvents and biological tests showed that the mycotoxins came off in the diethylether, chloroform and mostly in the ethyl acetate fractions. Use of different available mycotoxin standards on silica gel G coated chromatoplates revealed that 1 of the mycotoxins produced by A quadrilineatus was sterigmatocystin. Two other more toxic mycotoxins were isolated and purified from the crude chloroform extract; their column, preparative thin-layer chromatographic, infrared and UV-spectrophotometric characteristics were established. The infrared spectra of the 2 purified mycotoxins suggested that the carbonyl group of their structures were similar to that of aflatoxin. PMID- 8351791 TI - Determination of the toxicity of molasses in Nubian goats. AB - Molasses at 10, 30 or 50% of the diet for 12 w was not toxic to goats and could be used as an inexpensive substitute for sorghum grain. No animals showed signs or lesions of illness attributable to feeding molasses. There were no differences among treatment groups in any of the following parameters: WBC, RBC, PCV, Hb, MCV, MCHC, GOT, uric acid, urea, cholesterol, and zinc. Serum creatinine, total protein, iron, copper, magnesium and calcium varied between groups but remained within the ranges for normal goats. Feedlot performance indicated that utilization of molasses energy for body weight gain was a function of intake; feeding 50% dietary molasses did not produce economic weight gain. PMID- 8351792 TI - Effect of dehydroproline as a collagen synthetic inhibitor in paraquat-induced pulmonary fibrosis in beagle dogs. AB - To investigate the effect of 3,4-DL-dehydroproline (DHP) on paraquat (PQ)-induced pulmonary fibrosis in beagle dogs, 25 beagles without distinction of sex were allocated at random into 2 groups; 17 dogs were PQ-dosed and 8 were saline-dosed. The 17 dogs were given 1 mg PQ/kg/d sc for 7-11 d; 14 of the 17 had decreased body weight on day 11 and were selected, 2 of which were determined at random and necropsied. The remaining 12 dogs were randomly divided into 2 groups of 6 dogs each (DHP-treated or saline-treated). They received either 25 mg DHP/kg/d sc or saline for 14 d and were sacrificed for measurement of lung lipid peroxide and lung hydroxyproline (Hyp) concentrations on day 25 or 180 after the PQ administrations started. Two of the 17 dogs (11.8%) given 1 mg PQ/kg/d sc died on days 9 and 11 of the administration. One dog (5.9%) had no signs of PQ toxicity including no decrease in body weight. The remaining 14 dogs (82.4%) had decreased body weight until day 11 of the PQ administrations. No significant differences in erythrocyte superoxide dismutase, blood catalase and serum-lipid peroxide occurred from the PQ dosing; however, lung lipid peroxide increased 4-fold. On day 180 the lung lipid peroxide of the PQ + saline treated group was still 4 times elevated, while the PQ + DHP treated group had about 1/2 that value. Lung Hyp concentrations in the PQ dosed dogs were significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351793 TI - Acute and subchronic oral toxicity of technical quinalphos in rats. AB - The organophosphate insecticide quinalphos is extensively used in agriculture. Information on the mammalian toxicity of quinalphos is limited. The acute po LD50 of technical quinalphos was 19.95 mg/kg in males and 13.78 mg/kg in female rats. Administration of 0.75, 1.50 or 3.0 mg/kg/d technical quinalphos for 90 d po to rats produced poisoning and death. Male rats were more susceptible to quinalphos than female rats in the subchronic toxicity studies based on mortality, enzyme profiles and cholinesterase inhibition. PMID- 8351794 TI - Respiratory exposure of museum personnel to dichlorvos insecticide. AB - Dichlorvos (DDVP) is an organophosphate insecticide used to protect museum specimens from insect pests. Respiratory exposure of museum personnel to DDVP has not been studied previously. Analysis of air samples from museum rooms where DDVP was being used when the ventilation system was "on" showed a lower and significantly different (p = 0.025) amount of DDVP when compared to air samples collected from the same rooms when the ventilation system was "off". The DDVP concentrations of all samples collected were below the threshold limit value established by the American Conference of Governmental Industrial Hygienists. PMID- 8351795 TI - Suspected red maple (Acer rubrum) toxicosis with abortion in two Percheron mares. AB - Horses develop severe and often fatal hemolytic anemia after ingesting dried leaves from red maple (Acer rubrum) trees. Toxicosis appears related to an unknown oxidant present in the dried or wilted leaves. This case report describes 2 horses that aborted and developed fatal hemolytic anemia after consuming wilted leaves from red maple (Acer rubrum). While an absolute diagnosis was not confirmed due to lack of proper antemortem and postmortem examinations, red maple toxicosis appeared a reasonable diagnosis based on clinical signs and laboratory findings. Other differentials include equine infectious anemia, autoimmune hemolytic anemia, piroplasmosis, leptospirosis, ehrlichiosis, and other plant or chemical sources of oxidants (onion, garlic, kale, phenothiazines). PMID- 8351796 TI - Prolonged cardiopulmonary resuscitation during acute disopyramide poisoning. AB - A case is reported of sustained electromechanical dissociation due to deliberate disopyramide over-dosage in a young healthy girl. Circulatory recovery was achieved with standard resuscitative measures, including prolonged cardiac massage and isoproterenol infusion plus high dose calcium chloride. Neurological recovery was complete. PMID- 8351797 TI - Isradipine ingestion in a two-year-old child. AB - We reported the first case of accidental or intentional overdose with isradipine. A 2 y-old male accidentally ingested 2.5 mg of isradipine. A drop in arterial pressure responded to fluids. No other symptoms were noted. The child recovered without sequelae. PMID- 8351798 TI - Denatonium benzoate as a deterrent to ingestion of toxic substances: toxicity and efficacy. AB - When ingested at 10 ppm by human beings, denatonium benzoate has an extremely bitter, unpleasant taste. The addition of denatonium benzoate to liquid dish detergents and orange juice reduces the amount ingested by children. The toxicity of denatonium benzoate is low with acute po LD50's in rats of 485-740 mg/kg. The use of bittering agents, such as denatonium benzoate, could reduce the ingestion of toxic substances by dogs, cats, other animals and children and warrants further investigation. PMID- 8351799 TI - The effects of nitrate, nitrite, and N-nitroso compounds on animal health. AB - The clinical signs of acute nitrate toxicity vary according to species. In general, ruminant animals develop methemoglobinemia while monogastric animals exhibit severe gastritis. Nitrate ingestion has also been linked to impairment of thyroid function, decreased feed consumption, and interference with vitamin A and E metabolism. Hematologic changes seen with chronic high nitrate exposure include both compensatory increases in red blood cells and anemia, along with increased neutrophils and eosinophils. Unlike nitrate, nitrite is capable of inducing methemoglobinemia in a wide range of species, ie cattle, sheep, swine, dogs, guinea pigs, rats, chickens and turkeys. In rats, chronic nitrite exposure causes pathologic changes in a variety of tissues, alterations in motor activity and brain electrical activity, and alters gastric mucosal absorption. Nitrite affects the metabolism of sulfonamide drugs in animals such as the pig, guinea pig, and rat. The N-nitroso compound dimethylnitrosamine causes toxic hepatosis in cattle, sheep, mink, and fox. Nitrosamines have been reported in cows milk and been found to pass into the milk of goats under experimental conditions. PMID- 8351800 TI - Snake venom extractors: a valuable first aid tool. PMID- 8351801 TI - A role for Brachiaria decumbens in hepatogenous photosensitization of ruminants? PMID- 8351802 TI - Washington's pesticide panel: process and product. PMID- 8351803 TI - Lead non-poisoning in the Pacific Northwest. PMID- 8351804 TI - Suspected intoxications due to Lathyrus. PMID- 8351805 TI - The accuracy of intraoperative diagnoses based on examination of frozen sections. A prospective comparison with paraffin-embedded sections. AB - The accuracy of diagnoses based on examination of frozen sections was determined by comparing the results to those obtained by examination of tissues prepared using conventional methods (formalin fixation, paraffin-embedded tissue). One hundred ninety-four specimens were examined using the frozen section technique; 37 were examined to confirm a tentative diagnosis or to document lymph node metastasis and the remainder were examined to diagnose an unknown pathologic process. Of the 194 specimens examined, an accurate, specific diagnosis was obtained in 161 (83%); in 19 (10%), the pathologic process was correctly identified, but a specific diagnosis was not obtained; and in 2 (1%) the diagnosis was deferred. The remaining 12 (6%) were incorrectly diagnosed by the frozen section technique. When the number of specimens in which a specific diagnosis was obtained was combined with the number of specimens in which the pathologic process was correctly identified, the overall accuracy rate of the frozen section technique was 93%. There was no difference in the accuracy of the frozen section technique based on the reason for submission of the sample, source of tissue submitted, or the type of pathologic process (i.e., inflammatory or neoplastic). Of the 12 incorrect diagnoses, 4 (33%) were because of sampling errors and 8 (67%) were caused by interpretation errors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351806 TI - Cystourethropexy to correct refractory urinary incontinence due to urethral sphincter mechanism incompetence. Preliminary results in ten bitches. AB - Cystourethropexy was performed in 10 bitches with refractory urinary incontinence due to urethral sphincter mechanism incompetence. All animals had an abnormally shaped vesicourethral junction. The bladder neck was located in the pelvic canal in nine dogs (pelvic bladder). Surgery alone restored urinary continence in two cases and markedly improved incontinence in two cases. Surgery combined with medical therapy (phenylpropanolamine, 1.5 mg/kg orally once or twice a day, using a sustained-action preparation) restored urinary continence in four cases and markedly improved continence in one case. Surgery, with medical therapy, was completely ineffective in one case. No major complications were encountered in any dogs. In four cases, histopathologic evaluation of the dorsal bladder wall and neck revealed the presence of a single, perinuclear, clear vacuole in the cytoplasm of smooth muscle fibers. Electron microscopic examination showed that the vacuoles represented a dilatation of normal membrane organelles. Such abnormalities have the potential to alter the smooth muscle motility. This study indicates that cystourethropexy alone restored urinary continence only temporarily in the majority of the patients. The significance and frequency of the histopathologic findings requires further investigation. PMID- 8351807 TI - Clinical and pathologic effects of a modified technique for application of spiral prostheses to the cervical trachea of dogs. AB - A modified surgical technique for application of extraluminal polypropylene spiral prostheses (PSP) to the trachea was developed. A portion of the segmental blood supply to the collapsed segment of trachea was maintained by fenestrating rather than completely dissecting the right lateral pedicle. Polypropylene spiral prostheses were applied to the cervical trachea of 12 dogs (group I) via the modified technique and to 12 dogs (group II) with the identical surgical dissection but without PSP applied. Clinical abnormalities included mild coughing in group I dogs and swelling of the incisions in both groups. Limited necrosis and moderate degeneration and inflammation were observed histologically in both groups. Pathologic changes were worse in the caudal cervical segment of the trachea. Mucosal regeneration was present on day 10 in both groups. Transmural tracheal necrosis was not observed. The modified technique for application of PSP is recommended by the authors because it provides adequate surgical exposure and the blood supply preserved by segmentally dissecting the right lateral pedicle is adequate to maintain tracheal viability. PMID- 8351809 TI - Use of ultrasound in horses for diagnosis of left dorsal displacement of the large colon and monitoring its nonsurgical correction. AB - During a 28 month period, 82 horses with clinical signs of abdominal pain were examined for left dorsal displacement of the large colon (LDDLC) using percutaneous ultrasound. Left dorsal displacement of the large colon was diagnosed when a gas echo dorsal to the spleen obliterated the dorsal splenic border, or when the colon was observed lateral to the spleen. In 42 horses, ultrasound confirmed a diagnosis of LDDLC and 40 horses had no evidence of LDDLC. There were five false negative results and no false positives. In four horses with LDDLC, the colon was displaced between the spleen and body wall; three of these colic episodes resolved with medical therapy and the fourth required a celiotomy to relieve a sand impaction. The remaining 38 horses had a renosplenic entrapment; surgical correction was elected in 4 horses, 21 horses were corrected by a nonsurgical rolling procedure, 12 were corrected at surgery after an unsuccessful rolling attempt, and one was corrected by rolling but required surgery later because of an additional lesion. Percutaneous abdominal ultrasound was a valuable aid in the diagnosis of LDDLC and in confirming correction of the displacement after a nonsurgical rolling procedure. PMID- 8351808 TI - Quantitative ingrowth analysis of a porous-coated acetabular component in a canine model. AB - Histomorphometric analysis of bone ingrowth into a porous-coated acetabular component was evaluated in a canine model. A total of nine prostheses were evaluated, 3 at 6 months, 3 at 12 months, and 3 at 24 months after implantation. All implants were grossly stable at the time of retrieval. The mean percentage of bone ingrowth was 12% at 6 months, 24% at 12 months, and 24% at 24 months. Narrow radiolucent lines noted on microradiographs were more evident at the 6 month time period than at the 12 or 24 month time periods. Bone ingrowth into a porous coated acetabular component in a weight-bearing model may continue beyond the 6 month time period, and early evaluation of bone ingrowth may underestimate final bone ingrowth. PMID- 8351810 TI - Palmar digital neurectomy in horses. 57 cases (1984-1990). AB - The medical records of 57 horses that had palmar digital neurectomy performed between 1984 and 1990 were reviewed. Neurectomies were performed either by transection and electrocoagulation (47 horses) or by the guillotine technique (10 horses). Middle-aged geldings, Quarter Horses, and Thoroughbreds were significantly over-represented when compared with the hospital population. Horses used as hunter/jumpers also appeared to be over-represented. Complications occurred in 17 (34%) of the 50 horses for which follow-up information was obtained. Recurrence of heel pain was the most common complication (14 horses). Palpable painful neuromas were detected in three horses. One year after neurectomy, 74% of the horses were sound; this decreased to 63% after 2 years. PMID- 8351811 TI - In vivo investigation of communication between the distal intertarsal and tarsometatarsal joints in horses and ponies. AB - The frequency of communication between the tarsometatarsal and distal intertarsal joints was investigated in 27 horses and 12 ponies. After the injection of diluted latex into the tarsometatarsal joints using the plantarolateral approach, the horses and ponies were walked for 200 meters. Latex was found in the distal intertarsal joints of 19 of 73 tarsi (26% communication) at necropsy. In 3 tarsi, latex was also found in the proximal intertarsal and tarsocrural joints. PMID- 8351812 TI - Lateral patellar luxation in miniature horses. AB - Bilateral luxation of the patella in four Miniature Horses was corrected by a lateral release incision and medial imbrication of the parapatellar fascia to the tendon of the sartorius muscle. Before surgery, the four horses had a grade 3 to 4 lateral patellar luxation bilaterally and had difficulty walking. Trochlear ridge hypoplasia was evident on radiographs in each horse. Follow-up information varied from 11 months to 4 years after surgery. Three horses had no patellar luxation or lameness. The other horse had a normal right stifle, but patellar luxation (grade 3) had recurred on the left. PMID- 8351813 TI - Correction of patellar luxation by recession sulcoplasty in three foals. AB - Lateral luxation of the patella in four femoropatellar joints of three foals was repaired by recession sulcoplasty and medial imbrication of the joint. One foal was euthanatized because of septic arthritis caused by incisional dehiscence, and the other two foals were normal 2 years after surgery. Recession sulcoplasty combined with medial imbrication of the joint capsule resulted in a functional femoropatellar joint and should be considered in foals affected with lateral patellar luxation. PMID- 8351814 TI - Hepatic lobe torsion as a cause of colic in a horse. AB - A 14-year-old Arabian gelding was examined for colic. An exploratory celiotomy was subsequently performed and the left lobe of the liver was found to be twisted. The lobe was resected using a TA-90 surgical stapling instrument. Histologic examination of the resected liver indicated portal vein and sinusoid dilation and congestion with blood. There were focal areas of necrosis and bacterial cocci and rods throughout the section. The histologic findings were consistent with hepatic lobe torsion. After surgery, the horse was treated with broad spectrum antibiotics, anti-inflammatory drugs, heparin, and intravenous fluids. The horse recovered without complications, although serum liver enzymes remained elevated for more than 1 week after surgery. Seven months after surgery the horse showed no adverse affects from the disease. PMID- 8351815 TI - Epidural morphine in goats after hindlimb orthopedic surgery. AB - Morphine (0.1 mg/kg) diluted with 0.9% saline to a volume of 0.13 mL/kg was administered into the epidural space at the lumbosacral junction in 10 halothane anesthetized goats immediately before discontinuation of halothane. The same volume of 0.9% saline was given to control group of eight anesthetized goats. Both groups had undergone an orthopedic procedure that replaced the anterior cruciate ligament with a patellar tendon autograft. The appearance and unprovoked behavior of goats in the morphine group were significantly different (p < .05) from the saline groups. The goats in the morphine group were more sedate and struggled less during recovery. Epidural morphine did not produce respiratory depression or bloat during a 9 hour observation period. Heart rate, respiratory rate, and blood pressure (mean, systolic, and diastolic) of the morphine group did not differ from those of the control group. PMID- 8351816 TI - Effects of thiopental, ketamine, diazepam, xylazine, and nitrous oxide on EEG spike activity and convulsive behavior during enflurane anesthesia in atropinized cats. Effect of increasing inhalant concentrations. AB - The effects of thiopental, ketamine, diazepam, xylazine, and nitrous oxide, and the combinations of thiopental-nitrous oxide and ketamine-nitrous oxide, on both enflurane-induced electroencephalographic (EEG) spike activity and convulsive behavior were measured quantitatively in atropinized cats receiving enflurane with controlled ventilation. Pretreatments with thiopental, ketamine, and diazepam reduced both EEG spike frequency and amplitude at 2.5% to 4.5% inspired enflurane but did not abolish spike activity. Nitrous oxide (66% of inspired gas) did not significantly alter spike frequency or amplitude during 2.5% to 4.5% inspired enflurane, but the combination of thiopental-nitrous oxide or ketamine nitrous oxide reduced EEG spike activity during 2.5% inspired enflurane. Enflurane-induced convulsive score was markedly suppressed by thiopental and ketamine and was significantly reduced by diazepam, xylazine and nitrous oxide. The combinations of thiopental-nitrous oxide and ketamine-nitrous oxide greatly reduced behavioral-convulsive responses induced by 2.5% to 4.5% inspired enflurane. PMID- 8351818 TI - Different anisotropies for texture and grating stimuli in the visual map of cat striate cortex. AB - A comparison was made of the directional preferences of cat area 17 cells tested with two different stimuli, gratings and random-dot patterns. Depending on the stimulus, different distributions of direction preferences (anisotropies) were found in the same cells of the central representation of upper layers. With gratings most common preferred directions were vertical and horizontal. With textures, however, horizontal preferred directions were most common. In contrast, lower layer neurons had a bias for vertical preferred directions regardless of the type of stimulus used. PMID- 8351817 TI - Effects of thiopental, ketamine, diazepam, xylazine, and nitrous oxide on EEG spike activity and convulsive behavior during enflurane anesthesia in spontaneously breathing atropinized cats. Effect at surgical depth. AB - The effects of thiopental, ketamine, diazepam, xylazine and nitrous oxide, and combinations of thiopental-nitrous oxide and ketamine-nitrous oxide on electroencephalographic (EEG) spike activity and convulsive behaviors in atropinized cats at surgical depth of enflurane anesthesia were assessed quantitatively for 60 minutes during spontaneous ventilation. Mean inspired enflurane concentrations (MIEC) were reduced 16% to 29% by pretreatment with thiopental, ketamine, diazepam, and xylazine, and were reduced 19% by 66% nitrous oxide. The MIEC of cats anesthetized with thiopental-nitrous oxide-enflurane and ketamine-nitrous oxide-enflurane were 35% to 38% lower than that with nitrous oxide-enflurane. Pretreatment with thiopental, ketamine, diazepam, and xylazine did not reduce the EEG spike frequency during anesthesia but did markedly reduce the spike amplitude. The addition of 66% nitrous oxide did not alter the spike frequency during anesthesia but tended to reduce the spike amplitude. Combinations of thiopental-nitrous oxide and ketamine-nitrous oxide almost abolished the spike activity. The addition of 66% nitrous oxide prevented convulsive responses elicited by photic and auditory stimulation during enflurane anesthesia. Treatment with thiopental, ketamine, diazepam and xylazine, and combinations of thiopental-nitrous oxide and ketamine-nitrous oxide, completely prevented convulsive responses during enflurane anesthesia. PMID- 8351819 TI - Coding for stimulus velocity by temporal patterning of spike discharges in visual cells of cat superior colliculus. AB - Statistical analyses, performed on extracellularly recorded spike trains generated by 69 single motion sensitive visual cells in the intermediate layers of superior colliculi of pretrigeminal cat preparations, revealed that--even in the unstimulated condition (38/69)--most neuronal spike discharge patterns tended to switch between two stochastically distinct states, in the form of rapidly alternating "bursting" (high frequency) and "resting" (low frequency) episodes. The numbers of consecutive interspike intervals within a given state were, as a rule, independent integer-valued random variables with discrete probability distributions, in essential agreement with the semi-Markov model proposed by Ekholm and Hyvarinen [(1970) Biophysical Journal, 10, 773-796]. The introduction of visual stimuli (47/69) moving with velocities of 2-160 deg/sec caused systematic and reproducible changes in the ratio of bursting to resting activities, decreases in overall discharge variability, and increases in signal transinformation flow. Moreover, with one group of stimulated cells (28/47), increasing stimulus velocity caused increasingly precise ("stimulus-forced") synchronization of bursting episodes with specific phases of stimulus movement; while for a smaller group (12/47), stimulus-related alternations between bursting and resting states assumed the form of semi-rhythmical burst discharges within the characteristic 60-80 Hz "gamma oscillation" range ("stimulus-induced" synchronization). For a minority of cells (7/47), switching between bursting and resting states--although characteristically modified by stimulus velocity- remained largely desynchronized with all phases of stimulus transit. It was argued that such temporal patterns of discharge may constitute elements of a candidate "distribution" code for movement detection by the cat visual system. PMID- 8351820 TI - An illusory transformation of optic flow fields. AB - We compared a human observer's ability to locate the focus of expansion (FOE) of a radial optic flow field when this flow field was either combined with, or overlapped by, planar motion. With combined stimuli, in which the FOE was displaced in the direction opposite to the planar motion, subjects accurately located the displaced FOE. With overlapping (transparent) stimuli and the FOE remaining in the center of the display, we found an illusory transformation of the radial pattern: the focus of expansion appeared to be shifted in the direction of the planar motion. The speed of both the planar and radial patterns of motion influenced the illusion. Presence or absence of visual fixation had little effect. We suggest that this illusion might provide a clue as to the way the brain processes planar and radial motion which might in turn be relevant to the interaction of the planar and radial motion components of optic flow fields. PMID- 8351821 TI - Errors in direction-of-motion discrimination with dichoptically viewed stimuli. AB - At durations shorter than about 150 msec, a complex grating comprising a static 1 c/deg grating and a moving 3-c/deg grating is perceived as moving in the direction opposite that of the physical direction of motion. Here the phenomenon is further examined by measuring the perceived direction of motion of the fused images of a 1-c/deg grating presented to one eye and a moving 3-c/deg grating presented to the other. The strength of the illusion is almost unaffected by dichoptic presentation. This observation is consistent with the hypothesis that perceived motion is a consequence of the way the visual system integrates signals arising from different detectors tuned to the two component gratings. PMID- 8351822 TI - A study of women heterozygous for colour deficiencies. AB - We have examined the colour vision of 43 female subjects in the age range 30-59 yr of whom 31 were obligate carriers of various forms of colour deficiency and the rest were women who had no known colour-deficient relatives. In the case of all the carriers we established the phenotypes of their colour-deficient sons. As a group, carriers made significantly more errors on the Ishihara plates and showed enlarged matching ranges on the Nagel anomaloscope, but we could not replicate earlier reports of increased error scores on the Farnsworth-Munsell 100 Hue test or of systematic shifts in Rayleigh match mid-points. We did find that the colour matches of carriers of deuteranomaly were significantly displaced from those of normals in a ratio-matching task in which a mixture of 546 and 600 nm was matched with a mixture of 570 and 690 nm. Owing to X-chromosome inactivation, women who are heterozygous for anomalous trichromacy ought to have at least four types of cone in their retinae and we ask whether this affords them an extra dimension of colour vision, by analogy to New World monkeys where heterozygous females gain trichromacy in a basically dichromatic species. Many carriers of anomalous trichromacy exhibited no evidence for tetrachromacy, in that they accepted large-field Rayleigh matches following a rod bleach and they were unable to set unique matches in our ratio-matching task. However, eight carriers of anomalous trichromacy--and no other subject--refused large-field Rayleigh matches; and we found one carrier of deuteranomaly who was apparently able to make unique matches in the ratio-matching task. PMID- 8351824 TI - Sensory and attentional components of slowing of manual reaction time to non fixated visual targets by ipsilateral primes. AB - Reaction time (RT) for detecting extrafoveal targets is lengthened by a non informative prime at the same location or in the same hemifield (RT inhibition). We assumed that sensory effects at primed locations should be the same for unilateral and bilateral primes, whereas systematic covert orienting to a primed location should occur only with unilateral primes. We found equal RT inhibition for both types of primes at 0.2 sec prime-target intervals (SOA), as contrasted with inhibition for unilateral but not bilateral primes at 0.6 sec SOAs. We conclude that RT inhibition involves a succession of sensory components and orienting-dependent components. PMID- 8351823 TI - Assessment of foveal cone photoreceptors in Stargardt's macular dystrophy using a small dot detection task. AB - We measured frequency-of-seeing curves for tiny (1.125 and 3.375 min arc) stimuli flashed briefly at absolute threshold to estimate the density of foveal cones in normals and in subjects with Stargardt's macular dystrophy. Foveal absolute thresholds for Stargardt's were elevated 1.5 log units over normal. Analysis using Poisson counting statistics indicated that the quantal absorption to stimulate individual cones was normal for Stargardt's but that effective optical density of individual cones was reduced by > 1 log. Numerical density of foveal cones was reduced 1 log unit for Stargardt's patients with acuities of 20/30 20/100. PMID- 8351825 TI - An orientation-tuned component in the contrast masking of stereopsis. AB - A masking paradigm was used to evaluate the orientation selectivity of the mechanisms mediating human stereopsis. Two experienced and eleven naive observers viewed stereograms, spatially filtered to contain contrast energy with Gaussian passbands in spatial frequency and orientation. Using forced-choice procedures we measured contrast thresholds for stereopsis in the presence of oriented masking patterns. Our results show that the masking of stereopsis consists of two components: one is orientation dependent, the other is non-oriented and has greatest magnitude at lower spatial frequencies. Contrary to an earlier study, these results imply that stereopsis mechanisms may have similar orientation tuning to mechanisms mediating contrast detection. PMID- 8351826 TI - Effects of the spatial frequency of test and reference stimuli on stereo thresholds. AB - The perceived depth of adjacent regions of stereoscopic stimuli may be influenced, in part, by differences in the spatial frequency composition of adjacent stimuli. Consequently, it would be predicted that, if the test and reference stimuli differ in their spatial frequency composition, depth discrimination thresholds should be asymmetric about the retinal disparity of the reference stimulus. We measured depth discrimination thresholds with test and reference stimuli that differed by up to 2 octaves in their spatial frequency composition. Stereo-thresholds decreased as a function of spatial frequency to about 2-4 c/deg and were then constant. However, in contrast to the predicted effects, our results show that, for the range of spatial frequencies used, differences of up to 2 octaves in spatial frequency, between test and reference stimuli, do not affect depth discrimination thresholds. PMID- 8351827 TI - Precision of stereoscopic depth perception from double images. AB - The increment depth discrimination function was originally described by Ogle [(1953) Journal of the Optical Society of America, 43, 906-913] as a single exponential function. In contrast, recent studies have suggested that a two component function better describes increment depth discrimination. To determine the relative effects of stereoscopic and non-stereoscopic width cues on the form of the function, we measured increment depth discrimination under conditions where both stereoscopic and dichoptic width cues were available. We found that increment depth discrimination data were well described by two-segment functions if both stereoscopic and dichoptic width cues were available. However, when dichoptic width cues were eliminated, by randomizing the pedestal disparity (crossed or uncrossed disparity) between trials, the increment depth discrimination function was better described by a single exponential function. This result has important implications for models of stereoscopic depth processing because it shows that stereoscopic depth discrimination thresholds progressively increase as a function of distance from the horopter. PMID- 8351828 TI - On the perceptual identity of dynamic stereopsis and kinetic depth. AB - This paper presents a set of experiments demonstrating novel interactions between kinetic depth (depth-from-motion) and dynamic stereopsis (depth-from-disparity). Previous research has shown that adaptation to a moving stereoscopic figure influences the subjective percept of a subsequently viewed kinetic depth figure. In this paper the interactions between kinetic depth and dynamic stereopsis are shown to be very robust and to occur in situations involving perceptual priming. It is also found that kinetic depth and dynamic stereo stimuli are indistinguishable when the stereoscopic stimulus has small, but perceptually salient, disparity. These results are consistent with the hypothesis that stimuli for kinetic depth and for dynamic stereopsis engage a common neural network. PMID- 8351829 TI - The role of Fourier components in discrimination between two types of plaid patterns. AB - Do decision processes have separate access to the individual Fourier components of a complex pattern? Subjects discriminated between plaid patterns formed by multiplying or by summing vertical and horizontal square-wave gratings. Such patterns differ in two ways: (1) product plaids contain distinctive off-axis Fourier components; (2) adjacent luminances are related by equal ratios in the products and by equal differences in the sums. Performance on this task was compared with the separately measured unmasked detection thresholds of the off axis Fourier components and with performance in control tasks which provided only the non-Fourier cues. Performance in the plaid discrimination was worse than predicted from the unmasked detection thresholds, but better than predicted from the control tasks. The results argue that Fourier components are accessible, but that masking reduces their usefulness. PMID- 8351830 TI - Active vision and the identification of three-dimensional shape. AB - We examined the performance of human observers to identify three-dimensional (3D) shape from motion induced by exploratory head movements. Subjects categorized 3D quadratic surfaces with randomly chosen shape but with a fixed amount of curvature in one of eight shape categories. Human observers had their best performance with convex parabolic and concave parabolic shapes, but had more difficulties in identifying the hyperbolic shapes. The identification of 3D shape was not significantly influenced by the amount of curvature. This means that our description of 3D shape closely matches the intuitive notion of shape, and that its use in 3D shape perception tasks is justified. PMID- 8351831 TI - Another means for measuring the motion aftereffect. AB - A new procedure for measuring the motion aftereffect (MAE) is described. The procedure involves adaptation to an animation sequence depicting dots moving in a given direction followed by presentation of a test sequence depicting dots moving in all possible directions. Under adaptation, the test sequence appears to have a directional bias opposite the direction experienced during adaptation. This MAE can be nullified by viewing an animation sequence in which a percentage of dots is constrained to move in a direction opposite the aftereffect. Using a method of constant stimuli, this percentage can be varied to find the value yielding incoherent motion. This dynamic MAE exhibits the same characteristics as the conventional MAE. PMID- 8351832 TI - Visual pigments and oil droplets in genetically manipulated and carotenoid deprived quail: a microspectrophotometric study. AB - The spectral absorbances of visual pigments and retinal oil droplets were studied in three groups of Japanese quail (Coturnix coturnix japonica): an unselected control population and two artificially selected strains that exhibited different early approach preferences between blue and red stimuli. The oil droplets were examined with and without prior carotenoid deprivation. Four cone pigments and five oil droplet types were identified, resembling those in other avian species. Carotenoid deprivation eliminated all pigmentation detectable in oil droplets by microspectrophotometry. Placement of chicks on normal diet gradually reintroduced normal pigmentation within the span of about a week. No statistically significant differences were found between normal and genetically selected birds in either visual pigments or oil droplet types, or in their relative proportions. It is concluded that differences in the early colour preferences of quail are unlikely to be a result of variation in the spectral properties of their photoreceptors. PMID- 8351833 TI - Dendritic architecture of ON-OFF direction-selective ganglion cells in the rabbit retina. AB - ON-OFF direction-selective ganglion cells in rabbit retina have bistratified dendritic arbors that are formed by contributions from three or four primary dendrites and their dependent branches (dendritic systems). Most dendritic systems contribute to both branching planes, but some are confined to a single plane. The way in which dendritic systems combine to form the branching planes varies from cell to cell, but the dendritic systems always produce a non overlapping tiling of the planes having a distinctive mesh-like appearance. This mesh-like pattern appears to be produced primarily by a large number of branches that terminate close to the cell somata. Despite clear differences in the detailed construction of the dendritic arbors, quantitative morphological attributes vary primarily with overall size, and the variation is nearly isometric. We therefore regard these cells as isomorphic, in the sense that they have developed according to the same rather liberal rules for dendritic growth. More importantly, however, we have not found any morphological feature that is correlated with the cells' preferred response directions. We conclude that the distinctive dendritic architecture of these cells is related to general requirements for dense, uniform sampling from specific input arrays, and not direction-selectivity per se. The most important rules governing the branching pattern of the ON-OFF direction-selective cells may be related to territoriality, wherein dendrites, dendritic systems, and cells of the same type establish non overlapping domains. PMID- 8351834 TI - Structural testing of multi-input linear-nonlinear cascade models for cells in macaque striate cortex. AB - Structural testing methods based on experimental white noise stimulus-response data were used to evaluate multi-input linear-nonlinear (LN) cascade models for simple and complex cells in macaque striate cortex. An LN structural test index, based on white noise stimulation, was developed and found to be suitable for classifying cells as simple vs complex. In particular, classification results based on the LN structural test index were similar to classification results based on a traditional modulation index derived from cell responses to drifting sinewave gratings. Judging from their structural test indices, complex cells deviated more strongly from LN behavior than did simple cells. Yet, even with simple cells, on average, only about 60% of the first- and second-order white noise stimulus-response relation was consistent with LN behavior. Just two of thirteen simple cells studied had an LN consistency level that exceeded 80%. Similar results were found in tests for consistency with an LNL model which includes an additional linear post-filter. We conclude that a conventional multi input LN network model may be a useful approximation to the response behavior of some simple cells. However, even during steady state stimulus conditions, subcortical and/or cortical nonlinearities other than a static output nonlinearity play a very significant role in shaping the responses of most simple cells in the macaque striate cortex. PMID- 8351835 TI - The effects of peripheral flicker on foveal spectral sensitivity. AB - A flickering surround reduced sensitivity to large, briefly flashed monochromatic stimuli superimposed on a steady white background, compared to sensitivity measured when the surround was steady. The flickering surround had no effect on stimuli that were large and of long duration or small in size. Increasing the diameter of the background reduced the magnitude of the effect, but did not eliminate it. PMID- 8351836 TI - Spatiotemporal properties of motion perception for random-check contrast modulations. AB - To clarify the mechanism of detecting the motion of contrast modulations, the spatiotemporal properties of direction discrimination for contrast motion were examined. The stimulus was a microbalanced random stimulus [Chubb and Sperling (1988) Journal of the Optical Society of America A 5, 1986-2007], termed random window kinematogram (RWK), a shifting random checkerboard pattern in which each check was either a patch of random dots (uncorrelated between frames) or a patch of uniform gray having the mean luminance of the random dots. The effect of exposure duration (ED) on RWK discrimination could be described as stimulus onset asynchrony (SOA) dependency when EDs of the first and second frames were the same, but the performance was better than predicted from SOA when the first ED was short while the second was long. RWK could be seen at longer inter-stimulus intervals than random-dot kinematogram (RDK) having similar stimulus parameters (e.g. check size, effective contrast). Incoherent motion (e.g. reversed phi) could be seen for RWK. Maximum displacement limit (Dmax) for RWK was comparable to that of RDK, but it increased in proportion to check size, while Dmax for RDK did not. These results suggest that the contrast motion mechanism extracts motion locally, and involves a correlation-type motion extraction stage similar to the luminance motion mechanism. In addition, the spatial ranges of the contrast motion detectors are comparable to those of the luminance motion detectors, but their temporal range is larger. The contrast motion mechanism is more scale invariant than the luminance motion mechanism. PMID- 8351837 TI - Pulse modulation detection in human motion vision. AB - We present data on the human sensitivity to temporal pulse modulations of target velocity. We measured threshold detection modulation amplitudes for pulse-shaped speed modulations, as a function of pulse duration and temporal frequency. At short pulse durations (up to 50 msec) and low modulation frequency (1 Hz), detection amplitudes are ruled by Bloch's law: the product of pulse duration and threshold modulation amplitude is a constant. This constant corresponds to a position modulation with an amplitude of 3 arc min in a coordinate frame that moves at the average speed (3 deg/sec) of the target. At longer pulse durations we find deviations from Bloch's law. Speed modulation thresholds are not critically dependent on target luminance contrast. These results are modeled by a modulation detection process in two stages. A functional description of the first stage is filtering of the true speed modulation signal by a second order low-pass filter with a characteristic time constant of 20-25 msec. The second (decision) stage is variance detection: modulations are detected when the variance of the filtered modulation function exceeds a certain threshold variance. The square root threshold variance is estimated 8-10%. This two-parameter model accurately predicts the measured dependence of pulse modulation detection thresholds on pulse duration and pulse density. PMID- 8351838 TI - Motion-based detection by 14-week-old infants. AB - Three experiments using standing wave stimuli with 14-week-old human infants are reported. Two competing hypotheses regarding the detection of these standing wave line stimuli were tested in these studies. Amplitude-based (positional) detection was contrasted with speed-based (motion) detection. Temporal oscillation frequencies of 0.15, 0.30, 0.60 and 1.20 Hz were used. The detectability of a standing wave of fixed amplitude was influenced significantly by the temporal frequency of the oscillation. By inference, the results of the three experiments supported the motion-based detection hypothesis. PMID- 8351839 TI - Spatial-frequency adaptation: evidence for a multiple-channel model of short wavelength-sensitive-cone spatial vision. AB - The frequency selective effects of spatial adaptation were measured with vertically-oriented, cosine stimuli upon an intense long-wavelength (yellow) field, which isolated the short-wavelength-sensitive (S) cones. Consistent with isolated-S-cone spatial threshold and masking results, the adaptation measurements demonstrate S-cones input to multiple, orientation selective, spatial frequency mechanisms. Moreover, the adaptation measurements show the minimum number of S-cone mechanisms is three. The frequency tuning of each mechanism was derived from the S-cone threshold and masking results. Two of the tuning curves are bandpass with peak sensitivities in a vicinity of 0.7 and 1.4 c/deg, respectively. These two closely resemble tuning curves derived from results with luminance-modulated stimuli. Confined to the range of frequencies examined (0.25-2.83 c/deg), the third tuning curve is lowpass with a high frequency cutoff of roughly 2.0 c/deg. However, subsequent measurements of orientation selectivity demonstrate the third mechanism to have bandpass frequency tuning as well. PMID- 8351840 TI - Distortions in two-dimensional visual space perception in strabismic observers. AB - Amblyopic subjects were asked to memorize circles of different radii (2, 4 and 6 degrees), and then to reconstruct them monocularly with each eye, point by point (12 points per circle). The resulting two-dimensional maps of visual space showed considerable distortions, including expansion, shrinkage and torsion of specific regions of the visual field of the amblyopic eye, but not the normal eye. Based on the differences between the two eyes, we computed complex two-dimensional patterns (gratings, checkerboards, optotypes, written text, natural scenes) as "seen" monocularly with the amblyopic eye. These reconstructed patterns were then compared with drawings of the same patterns observed through the amblyopic eyes of the same subjects. The reconstructed patterns only partially reflected the actual perception for the amblyopic eyes. The compensation of complex, globally extended scenes in comparison to the distortions obtained by local, punctate settings probably reflects cooperative interactions occurring at higher brain levels. PMID- 8351842 TI - Saccade-contingent displacement of the apparent position of visual stimuli flashed on a dimly illuminated structured background. AB - Subjects were required to perceptually judge the location of flash targets presented at the time of a saccade at various positions scattered two dimensionally on a dimly illuminated structured background. The saccade contingent mislocalization was shown only in the direction parallel to the saccade, and not in the direction perpendicular to the saccade. In addition, the mislocalization under the "illuminated background" condition was different in several respects from that observed when targets were presented in the dark. It was suggested that the mislocalization is successfully explained by assuming three physiological and cognitive processes: a sluggish activity of the extraretinal eye position signal, visual cues from the visible background, and selective inattention to image displacements. PMID- 8351841 TI - Binocular eye orientation during fixations: Listing's law extended to include eye vergence. AB - Any eye position can be reached from a position called the primary position by rotation about a single axis. Listing's law states that for targets at optical infinity all rotation axes form a plane; the so-called Listing plane. Listing's law is not valid for fixation of nearby targets. To document these deviations of Listing's law we studied binocular eye positions during fixations of point targets in the dark. We tested both symmetric (targets in a sagittal plane) and asymmetric vergence conditions. For upward fixation both eyes showed intorsion relative to the position that would have been taken if each eye followed Listing's law. For downward fixation we found extorsion. The in- or extorsion increased approximately linearly with the vergence angle. The direction of the Listing axis and the turn angle about this axis can be described by rotation vectors. Our observations indicate that for fixation of nearby targets the rotation vectors of the two eyes become different and are no longer located in a single plane. However, we find that it is possible to decomose the rotation vector of each eye into the sum of a symmetric and an anti-symmetric part, each with its own properties. (1) The symmetric part is associated with eye version. This component of the rotation vector is identical for both eyes and lies in Listing's plane. In contrast to the classical form of Listing's law, this part of the rotation vector lies in Listing's plane irrespective of the fixation distance. (2) The anti-symmetric part of the rotation vector is related to eye vergence. This component is of equal magnitude but oppositely directed in each eye. The anti-symmetric part lies in the mid-sagittal plane, also irrespective of fixation distance. For fixation of targets at optical infinity the anti-symmetric part equals zero and the eye positions obey the classical form of Listing's law. Thus, the symmetric and anti-symmetric parts of the rotation vectors are restricted to two perpendicular planes. Combining these restrictions in a model, with the additional restriction that the vertical vergence equals zero during fixation of point targets, we arrive at the prediction that the cyclovergence is proportional to the product of elevation and horizontal vergence angles. This was well born out by the data. The model allows to describe the binocular eye position for fixation of any target position in terms of the bipolar coordinates of the target only (i.e. using only three degrees of freedom instead of the six needed for two eyes). PMID- 8351843 TI - Perceptual fading of visual texture borders. AB - A light gray square was displayed on a background of dynamic two-dimensional noise. After 10 sec of steady eccentric fixation, the square disappeared completely and the region corresponding to it was "filled in" by dynamic noise from the surround. Furthermore, when the whole display was switched off, a persisting patch of dynamic two-dimensional noise was seen in the region corresponding to the gray square. This persistent patch could be seen for almost 10 sec on some trials, suggesting that a dynamic neural representation of the surrounding "twinkle" is being created in this region. The fading of the square was especially pronounced in peripheral vision. Also, displacing the square by a small distance was usually sufficient to restore its visibility but this distance increased with eccentricity. This may be a consequence of the progressive increase of receptive field size with eccentricity that has been noted in both area 17 and MT. The perceptual fading and "filling in" that we report concurs with the recent physiological observations of Pettet and Gilbert [(1991) Society for Neuroscience Abstracts, 17, 1090] and Gilbert and Wiesel [(1992) Nature, 356, 150-152] in area 17 of cats and primates. PMID- 8351844 TI - Modelling of orientation discrimination across the visual field. AB - In many visual tasks thresholds can be made equal across the visual field by increasing the size of peripherally presented stimuli by appropriate magnification. The parameter E2 represents the eccentricity at which foveal stimulus size must double in order to maintain performance equivalent to that at the fovea. We measured orientation discrimination for a set of line sizes at various eccentricities. Thresholds were successfully scaled by applying a scaling function estimated by a technique that requires no prior assumptions regarding the size of peripherally presented stimuli. E2 of 1.95 deg was found for orientation discrimination. From our results we were able to develop a single equation which predicts orientation discrimination thresholds for an average observer over a range of different eccentricities and line lengths. PMID- 8351845 TI - Application of a simple mechanical model of accommodation to the aging eye. AB - A simple model for the mechanics of accommodation in the human eye, previously proposed, is applied to the eye at different ages. Data from work by R. F. Fisher is used to derive values for the elasticity of lens-plus-zonules and data from work by G. W. H. M. van Alphen and W. Graebel is used to derive values for the elasticity of the choroid, each at a series of ages. The model is applied in two ways: (i) the elasticity of one component is allowed to change with age, while the other (and also ciliary muscle force) is held constant and the effect on accommodative amplitude is estimated; (ii) both elasticities are allowed to change with age, and muscle force is assumed to take on values producing a constant change in the radius of the "ciliary ring". It is shown that, in principle, age-related changes in choroid could account for a substantial component of the observed loss of accommodative amplitude, and it is suggested that this may be the case for monkeys, but not for humans. For the case of "all components changing", which is probably the case for humans, the ciliary muscle is likely to become stronger with age. PMID- 8351846 TI - Quantifying color constancy: evidence for nonlinear processing of cone-specific contrast. AB - Color constancy was studied by the method of comparing color samples under two different illuminants using a CRT color monitor. In addition to the classical approach in which one of the illuminants is a (standard) white, we performed experiments in which the range of differential illumination was extended by using pairs of lights that were both colored. The stimulus pattern consisted of an array of thirty-five color samples (including five neutral samples) on a white background. A trichromatic illuminant-object interaction was simulated analogous to that resulting from illumination by three monochromatic lights. The test samples, as seen under "test" and "match" illumination, were successively presented to the left and right eye (haploscopic matching). The data show systematic deviations from predictions on the basis of cone-specific normalization procedures like those incorporated in the Retinex algorithm and the von Kries transformation. The results can be described by a nonlinear response transformation that depends on two factors, receptor-specific sample/background contrast and the extent to which the illuminant stimulates the receptor system in question. The latter factor explains the deviations. These are mainly caused by the short-wave-sensitive system, as a consequence of the fact that this system can be more selectively stimulated than the other, spectrally less separated, cone systems. PMID- 8351847 TI - Psychophysical measures of illusory form perception: further evidence for local mechanisms. AB - Detection thresholds for a small light spot were measured at various distances from configurations (Kanizsa squares and other) consisting of white inducing elements on a dark background. Threshold distributions as a function of target position, number, size and spacing of contrast inducing elements were established. The data show that thresholds are elevated when the target is located close to one or more inducing element(s). Furthermore, threshold elevations diminish with increasing distance of the target from the configurations, increasing spacing and decreasing size of their inducing elements. When the target is flashed upon an illusory contour, no threshold elevation is observed in any of the conditions tested. Within incomplete illusory figures (only half of the square visible), the threshold gradients show the same tendencies. The present observations add further empirical support to the idea that illusory figures are built up by way of local mechanisms at early stages of processing. PMID- 8351848 TI - Movement direction analysers: independence and bandwidth. AB - Opponent, or ratio, models of movement direction perception propose that pairs of analysers, sensitive to opposite directions, are linked in an opponent fashion. Alternatively, distribution models posit independence of movement direction analysers. To investigate analyser independence, a direction-selective adaptation experiment was conducted in which motion coherence thresholds for random-dot apparent motion stimuli were measured for upward, downward, leftward and rightward motion with and without prior adaptation to rightward motion. Coherence thresholds for rightward motion were elevated on average by 0.64 log units after adaptation. Thresholds for motion in the other directions remained unchanged. Since opponent models predict enhanced sensitivity after adaptation for the direction opposite that of adaptation, these results suggest that movement direction analysers operate independently. In a second experiment subjects adapted to a bidirectional stimulus containing an equal number of leftward and rightward moving dots. Leftward and rightward coherence thresholds were elevated even though no motion aftereffects were produced. A third experiment in which coherence thresholds for test directions within a narrow range were measured with and without prior adaptation to motion in the direction of the range's mean showed that threshold elevation was maximal when test and adaptation direction were matched and fell off as the difference in adaptation and test direction increased. The resulting functions indicate that the bandwidth of movement direction analysers is between +/- 35 and +/- 40 deg, a value consistent with reported mean directional tuning functions of movement sensitive units in the middle temporal area but smaller than previously reported psychophysical values. PMID- 8351849 TI - Optical flow from eye movement with head immobilized: "ocular occlusion" beyond the nose. AB - The point of observation translates with eye movement because it is not coincident with the center of rotation in the eye. "Ocular occlusion" results. The amount of optical structure revealed by eye rotation depends on the distances of the occluding and occluded surfaces. The method of adjustment was used in Expt 1 to investigate the amount of structure detected at distances up to 1 m. In Expt 2, a forced-choice method was used to confirm predictions based on the assumption that the point of observation is in the entrance pupil at 11 mm from the center of rotation. (The location of the point of observation in the eye had not been measured previously.) Experiment 3 investigated the use of ocular occlusion to detect separation of surfaces in depth. PMID- 8351850 TI - The effect of transiency on perceived velocity of visual patterns: a case of "temporal capture". AB - We measured the points of subjective equality of velocity for dynamic unidirectionally moving random-dot patterns with different amounts of transiency. The transiency was changed by varying the time a dot would move before being randomly replotted within the stimulus. The perceived velocity of patterns moving at intermediate velocities (4 or 6 deg/sec) was increased by decreasing the point lifetime while no speedup was observed at high velocities (12 deg/sec). A speedup was also observed when a few stationary points of short lifetime were introduced into a stimulus. The non-directional transiency generated by these flickering points seems to be captured by the moving pattern and biases the velocity estimate. We term this phenomenon "temporal capture". The results are in agreement with models that determine velocity by comparing the activity in lower and higher temporal frequency channels. Our stimuli would selectively increase activity in high temporal frequency channels and thus lead to an increase in perceived velocity. PMID- 8351851 TI - Detecting and discriminating the direction of motion of luminance and colour gratings. AB - Human observers were required to discriminate the direction of motion of vertically moving, 1 c/deg luminance and colour gratings. The gratings had different contrasts and moved at temporal frequencies between 0.5 and 32 Hz. Sensitivity [the reciprocal of the contrast at which performance reached 75% correct in a temporal two-alternative forced-choice (2 AFC) discrimination task] was a band-pass function of temporal frequency for luminance gratings, and a low pass function of temporal frequency for colour gratings. Further, when colour contrast was expressed in terms of the modulation in cone excitation produced by the stimulus, sensitivity to colour gratings was greater than sensitivity to luminance gratings at frequencies below 2 Hz. On the other hand, at temporal frequencies above 4 Hz, sensitivity to colour gratings was comparable with sensitivity to luminance gratings of double the temporal frequency. Detection sensitivity was measured for luminance and colour gratings of 1, 4 and 16 Hz. With either colour or luminance gratings, detection thresholds were very similar to those for direction-of-motion discrimination. This result confirms findings of Mullen and Boulton [(1992) Vision Research, 32, 483-488] and Cavanagh and Anstis [(1991) Vision Research, 31, 2109-2148], but is different from that reported by Lindsey and Teller [(1990) Vision Research, 30, 1751-1761] who used a smaller stimulus seen in a parafoveal region and found that motion discrimination thresholds were higher than detection threshold for colour gratings. We repeated our threshold measurements using parafoveal viewing conditions similar to those used by Lindsey and Teller (1990). We found that, although for luminance gratings detection thresholds were very close to direction-discrimination thresholds, for colour gratings, they were lower. The result is in qualitative agreement with Lindsey and Teller (1990). Our results suggest that low-level, or "first-order" motion mechanisms are not as sensitive to chromatic gratings as are colour detection mechanisms. PMID- 8351852 TI - Integration of depth modules: stereopsis and texture. AB - Global shape judgements were employed to examine the combination of stereopsis and shape-from-texture in the determination of three-dimensional shape. Adding textural variations to stereograms increased perceived depth. Thus, texture was not simply vetoed by the strong stereo cue. In experiments where the depth specified by texture was incongruent with that specified by stereo, the data were well described by a weighted linear combination rule. Although only a small weight was assigned to texture, this weight was somewhat greater at a farther viewing distance. This could be a consequence of the decreased reliability of stereopsis at far viewing distances. PMID- 8351853 TI - Effects of different texture cues on curved surfaces viewed stereoscopically. AB - Stereoscopic shape judgements can be modified by the addition of texture cues. This paper examines the properties of texture that are responsible for this effect. When a three-dimensional curved surface is projected onto a two dimensional image, changes in surface orientation result in gradients of texture element size (or area), shape (compression) and density in the image. Manipulating each of these gradients independently we found that 97% of the variance in the results could be accounted for by the compression gradient. When the texture pattern corresponds to a highly anisotropic texture on the object's surface, shape-from-texture becomes ineffective. These results suggest that human shape-from-texture proceeds under the assumption that textures are statistically isotropic, and not that they are homogeneous. PMID- 8351854 TI - Saliency effects across dimensions in visual search. AB - In previous work it has been shown that search for an orientation target can only be done fast, and in parallel, when the target's orientation differs sufficiently from that of neighbouring lines. Targets with an increased local orientation contrast appear as salient and are immediately detected. In the present study, the effect of saliency from other stimulus dimensions was investigated. Five subjects were asked to look for vertical lines in texture-like displays, which were presented either embedded in the local orientation flow ("non-salient" target presentation) or at an increased feature contrast ("salient" target presentation). Saliency was obtained from local differences in orientation ("within dimension" saliency) or other visual cues ("cross dimensions" saliency), such as colour, luminance, motion, and disparity. Targets displaying cross dimensional saliency were always non-salient in the orientation domain. The results show that subjects were slower in detecting targets from non-salient than from salient presentations. The effect of saliency on visual search is not feature-specific and, in particular, is not restricted to the stimulus dimension in which target features are searched for. PMID- 8351855 TI - Magno and parvo visual channels and the subjective Necker cube. PMID- 8351856 TI - Dependence of speed and direction perception on cinematogram dot density. AB - In the present experiments, we find that with abrupt decreases in dot density of random-dot cinematograms, perceived speed decreases, while with abrupt increases in dot density, perceived speed increases. Further, in steady-state conditions, perceived speed is also affected in the same way, but to a lesser degree, by the dot density of cinematograms. Direction discrimination of random-dot cinematograms is enhanced when dot density increases abruptly from one stimulus to the next, but is degraded when dot density decreases abruptly. Finally, speed discrimination remains constant even when density changes abruptly. The perceived speed and direction-discrimination data are consistent with the Motion Coherence theory which motivated this study, and with models that include a smoothing stage similar to this theory. Of the other models that we consider, most predict that increasing dot density reduces perceived speed. The speed-discrimination data could not distinguish between the different theories. PMID- 8351858 TI - [Indications for cornary angiography]. AB - This is a summary of relative indications for the selection of patients for coronary angiography. Coronary angiography is an important part of clinical evaluation of patients with ischemic heart disease, valve heart disease, cardiomyopathies. Main groups of patients with ischemic heart disease are: angina pectoris after low levels of effort despite a good medical treatment, unstable angina, variant angina, angina with high risk of acute coronary syndromes from noninvasive exercise testing. In addition coronary angiography is indicated in patients with unexplained congestive heart failure, in patients with acute myocardial infarction with mechanical complication requiring cardiac surgery such as hemodynamically important mitral insufficiency, large ventricular septal defect or a large aneurysm leading to heart failure. Also in patients with sudden death syndrome unrelated to acute myocardial infarction. Patients with silent ischemia with known coronary artery disease and with known risk factors should undergo coronary angiography. Indication for coronary angiography is also in patients with hemodynamically important valvular, subvalvular or supravalvular heart disease in whom corrective surgery is contemplated. PMID- 8351857 TI - [The position of internal medicine in Europe. Report from a meeting of the presidents of European internal medicine societies]. PMID- 8351860 TI - [Sick sinus syndrome and permanent cardiac pacing]. AB - The authors submit a retrospective analysis of 140 patients with an affection of the sinoatrial node who had a permanent cardiac pacemaker. The analysis comprises an 18-month period; the patients were from the eastern Slovakian region. The authors emphasize different affections of the sinoatrial node and discuss various ways of permanent cardiac pacing and other types of non-pharmacological treatment (e.g. electric ablation). Diseases of the sinoatrial node account for as much as 40% of implantations of a permanent pacemaker on account of bradyarrhythmia. At the clinic this implies a quantitative increase of cardiac pacing on account of diseases of the sinoatrial node by 18%, as compared with a previous period (e.g. the average for 1978-1987). A qualitative change is the introduction of physiological permanent cardiac pacing. PMID- 8351859 TI - [Inhibition of thrombocyte activity in atherogenesis and thrombogenesis using isradipine and other calcium antagonists]. AB - Increased platelet activity on structurally and functionally impaired endothelium leads to a release of serotonin (5HT), thromboxane A2 and growth factors from platelets. These vasoactive substances may participate in the development of atherosclerosis and thrombovascular events. Platelet aggregatory response to 5HT increases with the height of blood pressure, age, smoking and plasma cholesterol levels. Lipoprotein fractions exert disparate effects an platelets. LDL cholesterol amplifies 5HT-induced platelet activation whereas HDL-cholesterol inhibits the amplifying effect of LDL-cholesterol. These results indicate that different effects of HDL and LDL-cholesterol on atherosclerotic progression that where found in epidemiological and population studies take place at a cellular level and may represent one of the underlying cellular mechanisms of atherogenesis. This mechanism may be relevant to both atherogenesis and acute thrombovascular events and therefore may represent a target of pharmacological intervention. Effect of calcium antagonists on serotonin- and LDL-induced platelet aggregation were investigated. Isradipin and verapamil (but not diltiazem, amlodipin and felodipin) inhibited at therapeutic concentrations platelet aggregation induced by 5HT in vitro. Isradipin (but not diltiazem and felodipin) also inhibited the amplifing effect of LDL-cholesterol on 5HT-induced platelet aggregation in vitro. Effects of isradipin on 5HT-induced platelet activity as well as on the amplifying effect of LDL-cholesterol were observed also ex vivo. Calcium antagonists differ in their platelet inhibition potency, including their effects on platelet response to 5HT and LDL-cholesterol. These platelet effects of Calcium antagonists appear to be neither group- nor class specific, but rather drug specific. Effect of isradipin may be relevant to platelet-mediated coronary vasospasm and to prevention of both atherogenesis and thrombogenesis. PMID- 8351861 TI - [Captopril in the treatment of congestive heart failure in acute myocardial infarct]. AB - The extent of affection of the heart muscle by infarction with subsequent left ventricular dilatation, remodelling and congestive failure is the decisive prognostic indicator of mortality. Inhibitors of ACE influence congestive heart failure in a favourable way and captopril reduces the morbidity and mortality in patients with still asymptomatic left ventricular dysfunction. The authors administered to a group of 23 patients with acute myocardial infarction and congestive heart failure (grade II according to Killip) small doses of captopril (4 x 6.25 mg/day)for a period of 10 days from the 1st-4th day after the onset of the disease). From ACE serum levels the effectiveness of these doses was assessed in keeping with data in the literature. As compared with a control group of 26 patients with similar haemodynamic conditions the authors did not find significant differences as regards improvement of the decompensation and in the mortality (a 3 patients in both groups). As to undesirable effects, arterial hypotension was recorded three times, twice minor proteinuria, once asymptomatic thrombocytopenia. Decisive for future therapeutic decision making are above all the results of the SAVE study which prefers captopril in patients with a yet asymptomatic left ventricular dysfunction. The authors are not quite convinced on the necessity to administer larger doses of captopril (up to 3 x 50 mg/day) in this indication. PMID- 8351862 TI - [Comparison of the effects and safety of atenolol and nifedipine in the treatment of angina pectoris]. AB - The effects of atenolol (100 mg/day) and nifedipine (60 mg/day) on angina symptoms and exercise tolerance were compared in an open, randomized study. Twelve-week treatment period was compared with two weeks of placebo treatment in 51 patients with chronic stable angina pectoris. Mean frequency of angina attacks decreased significantly from 8.3 to 1.6 attacks per week after atenolol treatment (p < or = 0.05). Both drugs increased exercise tolerance to development of signs of ischemia on electrocardiogram (p < or = 0.05) and increased maximal exercise tolerance as well (p < or = 0.05). Mean ST segment depressions at peak exercise were significantly decreased after treatment with atenolol and nifedipine (p < or = 0.05). Both drugs also increased total exercise capacity in comparison with placebo period, stated as 100%:192% after atenolol and to 191% after nifedipine. No significant changes of heart rate and blood pressure were noted during treatment period. Twelve patients did not finished study, two of them suffered myocardial infarction with death in one of them (atenolol group, other one nifedipine group). Thus, atenolol in one daily dose is as effective as nifedipine in chronic stable angina patients when administered as single therapy. PMID- 8351863 TI - [Significance of pulmonary vein flow for the determination of left ventricular filling pressure]. AB - The aim of the submitted study was to evaluate the blood flow in the pulmonary veins by transoesophageal Doppler echocardiography which is the ideal method for recording the blood flow in the pulmonary veins as the ultrasound probe is closely behind the left atrium. In 35 patients with ischaemic heart disease the authors evaluated the blood flow in the pulmonary veins to assess whether the rate of the blood flow in these vessels can serve a non-invasive estimate of the end-diastolic pressure in the left ventricle (LVEDP). It was revealed that venous blood flow has in the majority of cases two anterior peaks during ventricular systole, one anterior peak during diastole and one negative peak during atrial contraction. In patients with normal LVEDP the peak rate and integral time velocity of the flow curve is greater during systole, while in patients with a higher LVEDP these parameters are higher during diastole. Dopplerian assessment of the flow in the pulmonary veins is safe, relatively non-invasive and simple. This method makes possible rapid visual estimates of the end-diastolic pressure in the left ventricle. PMID- 8351864 TI - [Another source of hemorrhage--risks for patients with esophageal varices]. AB - The authors treated during the past three years 312 patients with oesophageal varices after the first haemorrhage. All patients were treated by endoscopic sclerotization of oesophageal varices and drugs which reduce the excessive portal pressure. After a minimum of two sclerotherapeutic sessions, following control of acute haemorrhage, the authors observed a relapse of haemorrhage from the upper gastrointestinal tract in 38 patients. In 20 of them the relapse of haemorrhage was again from oesophageal varices, but in 18 patients it was of different origin and would not be affected by classical treatment with a Sengstaken tube. The authors draw attention to the necessity of emergency endoscopy in these patients and to the fact that possible postponement of rational treatment, e.g. in duodenal ulcers insertion of a tube, may threaten the patient's life. PMID- 8351865 TI - [The effect of selective decontamination on malignant hematologic diseases treated with aggressive chemotherapy]. AB - The authors analyzed the course of 100 cycles of chemotherapy administered on account of haematological oncological disease: 66 cycles with administration of selective decontamination and 34 without its administration. Based on an analysis of the gut flora they provided evidence of the necessity of concurrent administration of originally separately administered antibiotics and of the necessity to replace nystatin by amphotericin B. They found a significant reduction of the incidence of infectious complications, the number of days with a body temperature above 38 and reduced consumption of antibiotics. The authors found a different composition of the agents causing infectious complications--a reduction of the ratio of Gram-negative agents and an increase of Gram-positive agents and fungi and also in increased percentage of fever of unknown origin. By analysis of the sensitivity of the detected microbes to antibiotics the authors assessed changes in the resistance caused by administration of selective decontamination and assessed the order of assumed effectiveness of the tested antibiotics. PMID- 8351866 TI - [Endothelial cells in tumors of the rectum and large intestine]. AB - In 40 controls and 102 patients with tumours of the rectum and large intestine the number of circulating anuclear cell residues of endothelial cells was investigated. The number of these endothelia in the blood of patients was significantly higher (p < 0.001) than in healthy subjects. After successful surgery of the tumour and subsequent chemotherapy the number of endothelia in venous blood reached normal levels with in 1-2 months. Conversely in patients where despite surgery secondaries were detected in other organs, the number of endothelia remained elevated. PMID- 8351867 TI - [Sjogren's syndrome]. AB - The authors present an account on Sjogren's syndrome--clinical manifestations, diagnosis, pathogenetic aspects and treatment. The diagnosis was based on three findings: keratoconjunctivitis sicca, stomatodynia--xerostomia and other immunological, diseases. The authors used different immunological examinations, bioptic examination of the oral mucosa and parotid glands. As to gastroenterological examinations, the gastric secretion is examined according to Lambling's method, the gastroduodenum is subjected to radiographic examination, endoscopy is performed as well as a bioptic examination of the gastroduedenal mucosa. PMID- 8351868 TI - [The effect of 2-aminoethylisothiouronium bromide on HLA antigens]. AB - Lymphocytes treated with a 6% and 4% AET solution after 60 or 120 minutes at 20 degrees or 37 degrees C display polyreactivity. Polyreactivity does not develop after short-term treatment (1-10 mins.). After treatment of lymphocytes with a 3% or 2% AET solution for a period of 20 or 30 mins. at 20 degrees or 37 degrees C the specific expresivity of HLA--A, B antigens rises; they are manifested, contrary to untreated lymphocytes, also by weak HLA sera. Addition of AET to the mixture of lymphocytes--HLA serum causes in the first stage of the microlymphocytotoxic test negativity of the test due to a block of the haemolytic activity of rabbit complement. PMID- 8351869 TI - [Therapy of refractory multiple myeloma. II. Therapy using high doses of alkylating cytostatic agents and radiotherapy in addition to interferon and bone marrow transplantation]. AB - The author presents part II of his review on the treatment of refractory myeloma. Treatment with large doses of melphalane, 140 mg/m2, was associated with a high death rate and therefore it is used nowadays only in combination with autologous transplantation or treatment with leucocytic growth factors (GM-CSF and G-CSF). Medium doses of melphalane (25 mg/m2 to 70 mg/m2) are tolerated better and are one of the possible approaches. Another possible therapeutic procedure is whole body irradiation. The advantage of extensive irradiation is rapid regression of pain. Interferon-alpha achieves a therapeutic response in some 20% of refractory patients. Finally the author presents some data on transplantation of bone marrow in patients with multiple myeloma. PMID- 8351870 TI - [Diabetes mellitus and the digestive tract]. AB - The author discusses in the submitted paper the important subject of manifestations of diabetes in the digestive tract--oesophagus, stomach, small and large intestine. Autonomous neuropathy, in particular a reduced tonus of the vagus, leads to a number of functional disorders which can produce diabetic dysphagia, gastroparesis, diarrhoea and constipation. The reduced tonus of the vagus, along with other factors, may lead to atrophy of the gastric mucosa and reduced gastric secretion. This explains the higher incidence of atrophic gastritis and other complications in diabetic patients. The author discusses also basic clinical aspects of these disorders and outlines therapeutic procedures. PMID- 8351871 TI - [Intracoronary "stents" in the treatment of ischemic heart disease. Brief review]. AB - The author present a brief review of the contemporary development of stents. Stents are used in the therapy of ischaemic heart disease, they are "tubes" inserted by methods of intervention cardioangiology into the coronary lumen to ensure their patency. At present they are indicated in particular in the treatment of acute arterial obliteration after PTCA. Stents used at present do not meet the demands required by long-term follow up. Stents used at present in clinical work are made from different metals. The authors describe also experimental experience with stents made from bioabsorbable materials which potentially appear to have much more suitable properties as regards maintenance of long-term patency of the affected artery. The properties of an "ideal stent" are described. PMID- 8351872 TI - [Variability of ECG changes in ambulatory Holter monitoring during treatment of hypothyroidism]. AB - The authors examined by 24-hour Holter monitoring the ECG in 20 patients treated on account of primary hypothyroidism with thyroid hormones. The patients were divided, with regard to the presence or absence of manifest ischaemic heart disease, into two groups which differed significantly as to the mean age of patients and the minimal R-R interval. In both groups diffuse ectopia was found without persisting activity except for one patient after myocardial infarction with relapsing ventricular tachycardia, organic sinoatrial blocks were found in two patients, an organic atrioventricular grade II block in one female patient and a functional (vagotonic) atrioventricular block of a higher grade in one female patient. Significant depressions of the ST segment, mostly of the asymptomatic type, were recorded in 55% of the patients, not differing in intensity and number of delevelings in positive patients of both groups. Comparison of mean circadian heart rates in relation to the type of substitution treatment revealed a minor tachycardic effect of one-component preparations containing levothyroxine only. PMID- 8351873 TI - [Blood component replacement in bone marrow aplasia in patients after aggressive chemotherapy for malignant hematologic diseases]. AB - Aggressive chemotherapy of malignant haematological diseases causes long-term aplasia of bone marrow and it is necessary to supplement blood elements repeatedly. When procuring blood derivates frequently dramatic situations develop. In an attempt to prevent alloimmunization of the patient by careful selection of the donor the time interval between indication and administration of the transfusion is prolonged. The objective of the present work was to attempt an estimate, as regards time and amount, for transfusion of blood derivates. The authors analyzed 100 cycles of aggressive chemotherapy with regard to changes of the haemogram. The group was divided arbitrarily with regard to the initial value of different components of the haemogram and for these portions of the group a time schedule of check-up examinations of the haemogram and of the assumed time of indication of transfusion of blood derivates was elaborated. In patients with an initial values of red blood cells above 3.5 x 10(12)/l the first transfusion is usually needed on the 8th day after the beginning of chemotherapy, in patients with a values lower than 3.0 x 10(12)/l after the initial supplementation a further drop may be expected already on the 4th day. Indication of replacement of thrombocytes can be expected in patients with an initial thrombocyte value above 120 x 10(9)/l cca on the 8th day, in patients with an initial thrombocyte value of 30 x 10(9)/l after initial replacement indication of another transfusion can be anticipated already on the 4th day after the beginning of chemotherapy. PMID- 8351874 TI - [Early empiric antibiotic therapy of infectious complications in patients with neutropenia]. AB - Aggressive chemotherapy used at present for the treatment of malignant haematological diseases leads to prolonged aplasia of the bone marrow with the possible development of fulminant infectious complications. Treatment of these complications must be started immediately when they are detected, i.e. as a rule without knowing the bacteriological finding at the time. The objective of the present work was to assess by analysis of 376 positive bacteriological findings from hospitalized patients with neutropenia and 141 findings of immunocompromised patients in their homes a combination of antibiotics for empirical treatment of infectious complications which developed during hospitalization or treatment at home. PMID- 8351875 TI - [Erythropoietin or transfusion?]. AB - The cause of anaemia in dialyzed patients is multifactorial. In the submitted paper the authors give an account of their experience with the treatment of 40 patients with erythropoietin (Eprex Cilag Co.). The initial Hb values were 78 +/- 13 g/l and haematocrit 0.24 +/- 0.03. After three months of treatment the haematocrit values were 0.30 +/- 0.02 and the Hb values 103 +/- 7 g/l. After one year's treatment haematocrit values were 0.31 +/- 0.03, Hb 105 +/- 10 g/l. Treatment was started by administration of 150 u/kg/week. Despite considerable individual differences the mean maintenance dose after one-year treatment is only 65 u/kg/week. In two patients treatment was discontinued. Treatment of anaemia in dialyzed patients with erythropoietin is effective and as compared with the risks of repeated transfusions, also economical. PMID- 8351876 TI - [The locomotor system in irreversible renal failure treated with regular dialysis]. AB - Changes of the locomotor apparatus in prolonged uraemia with regular dialyzation treatment determine the quality of life with all its consequences for the patient. The greatest impact on osteodystrophic disease (the most typical finding on the skeleton) is exerted by the length of dialyzation treatment. Of 216 patients having regular dialyzation treatment in 1979 to 1992 the authors observed osteodystrophic disease in 25, i.e. 11.6%. As to other most frequently observed changes they recorded osteoporosis in 12.9%, only very rarely osteomalacia and even osteopetrosis (1.8%). Carpal tunnel syndrome was recorded in 17.4% as a symptom of so-called dialyzation amyloidosis and in one man they observed the development of typical rheumatoid arthritis shortly after the onset of haemodialyzation. This is a rare observation not described in the literature so far. Crystalline arthropathy, incl. typical attacks of gout, were recorded only in 11 patients (5%). Changes on the locomotor apparatus in conjunction with irreversible renal failure with regular dialyzation treatment were recorded in 45%. It is important to differentiate findings which are not associated with uraemia and haemodialysis. This applies in particular to osteoarthritis deformans of the joints and spine. In major uraemic changes participates in particular secondary hyperparathyroidism. These changes comprise in particular osteolysis or even spontaneous absorption, erosive changes and destructive spondylopathy. Contemporary findings on the locomotor apparatus are so varied that they must be classified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351877 TI - [Aluminum osteopathy--experience with therapy]. AB - The author discusses the problem of aluminium osteopathy as one of the clinical manifestations of aluminium intoxication in dialyzed patients. She describes the case-histories of three patients treated on account of aluminium intoxication with desferrioxamine. The disease was manifested by pain in the bones and joints and muscular weakness, in two patients also with symptoms of encephalopathy. The diagnosis was assessed only after a special examination of bone trepanobiopsy (staining with aurintricarboxyl acetic acid) and confirmed by assessment of the aluminium serum concentration. While treatment of the first patient in 1986 was not successful, in another two female patients it proved possible by combined treatment (desferrioxamine and haemofiltration treatment) to eliminate the aluminium from the organism and to improve the symptoms. At present no longer aluminium hydroxide is prescribed as a routine binding agent of phosphates in the digestive tract. Therefore cases of aluminium intoxication are rare. Nevertheless it is important to pay attention to the problem of aluminium accumulation as its early diagnosis facilitates treatment. In the author's opinion the method of choice for elimination of aluminium from the organism is one-line haemofiltration combined with desferrioxamine. PMID- 8351878 TI - [Arthropathy and para-arthropathy in uremic patients on regular hemodialysis]. AB - Arthropathies and para-arthropathies occur in two thirds of regularly haemodialyzed uraemic subjects. The incidence does not depend on age but the period of haemodialyzation treatment. After five years of treatment the articular apparatus is affected in 100%. In women, as compared with men, the joints of the upper extremities, in particular the small joints of the hands are significantly more frequently affected. PMID- 8351879 TI - [Hyperparathyroidism and parathyroidectomy in dialyzed patients]. AB - The authors present older and more recent views regarding the pathogenesis of hypocalcaemia and secondary hyperparathyroidism in patients with chronic renal failure with emphasis on the impact of inorganic phosphate retention and lack of 1,25-dihydroxyvitamin D3 in body fluids. As regards therapeutic procedures the initial problem is to control hyperphosphataemia and to suppress the increased parathormone secretion in particular in dialyzed patients. When treating hyperphosphataemia it is necessary with regard to the severity of the finding to use concurrently several procedures and avoid aluminium phosphate binders. Aimed reduction of high parathormone levels in the blood stream can be achieved by medicamentous--pharmacological means, using 1,25 (OH)2 D3 or surgery of the hypertrophic parathyroid glands. The term parathyroidectomy can comprise also percutaneous infiltration of the parathyroid glands with ethanol. From this aspect under certain circumstances a combination of different therapeutic procedures may prove useful. In the conclusion the authors mention basic data on para-thyroidectomies performed in their department: the favourable long-term results of operations amounted to 80.4%. PMID- 8351880 TI - [The carpal tunnel syndrome, its diagnosis and therapy]. AB - Secondary amyloidosis is a complication typical for patients on long-term haemodialysis (HD). The first clinical signs are usually shoulder joint pain and CTS. We have questioned 74 patients who were on regular HD treatment and divided them into 3 groups according to the length of HD. Group I--on HD for 1-4 years: there were 35 patients in this group, 15 of them (i.e. 43%) had shoulder joint pain and/or CTS. None of these patients had such symptoms, which would require surgical treatment. Group II--on HD for 5-9 years: there were 22 patients in this group, 15 of them (i.e. 68%) had shoulder joint pain and/or CTS. 3 patients from this group had severe night pain and were therefore indicated for surgical treatment for CTS, each of them on 1 hand only. In 2 cases there was amyloid present in the histological examination. Group III--on HD for over 10 years: there were 17 patients in this group, 13 of them (i.e. 76%) had shoulder joint pain and/or CTS. 5 patients from this group were operated on both hands for severe night pain due to carpal tunnel syndrome. Only 1 patient had positive amyloid on both hands in the histological examination. All the 8 patients (i.e. 13 hands) were examined by EMG before the operation, showing reduction of motor conduction on n. medianus by 30.7 +/- 15.1%. After the operation the EMG control was done in 4 patients (7 hands), showing no improvement in 2 cases and in 5 cases the conduction on the n. medianus was found to be in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351881 TI - [Methods of measuring hyperinsulinism and insulin resistance]. AB - The author gives an account of methods used for evaluation of hyperinsulinism and insulin resistance such as: hyperinsulinaemic, euglycaemic and hyper- and hypoglycaemic "clamp", minimal model of glucose and insulin kinetics. They evaluate specially indexes used in clinical practice such as: I/G, (insulin/glucose--the so-called insulinogenic index), the G/I index, (the so called index of insulin resistance) and the index of C-peptide/IRI, basal and during the oral glucose tolerance test. In epidemiological studies of the prevalence of the X syndrome (5H) he recommends to use the G/I index basal and minimal two hours after a glucose load, along with assessment of C-peptide. It is thus possible to estimate not only insulin resistance but also hyperinsulinism and the ratio of distribution-utilization factors in the development of this hyperinsulinism. Hyperinsulinism need not be only hypersecretory but may be also associated with a reduced insulin utilization in the liver and peripheral target tissues. A hyperinsulinaemic response may be observed in four types of glycaemic curves after a glucose load: a in a normal curve, a flat curve, in impaired glucose tolerance and in a diabetic curve. According to the author the limiting value of the I/G index is 0.4 and the limiting value of the G/I index is 6 when the insulinaemia is expressed in mIU/l and the blood sugar level in mg%. The limiting level of insulinaemia after two hours is 63 mIU/l. The ratio of C peptide: IRI basal is cca 5:1 after a glucose load 2.5:1 when expressed in moles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351882 TI - [Management of war injuries in Vukovar]. AB - During 42 days of combat operations the brigade medical station provided surgical care for 535 wounded. One third of the wounded (31.8%) were classified in I or II grade of emergency. In the units were returned 21.7% of the wounded. Infusion therapy was applied in 47%. Laparotomy was performed in 7, drainage of the chest cavity in 19 and guillotine amputation of extremities in 11 wounded. The mortality was 1.9% at this stage. The way of management was imposed by combat operations, manpower and means available. PMID- 8351883 TI - [Surgical treatment of facial nerve paralysis in fractures of the temporal bone]. AB - Of 36 patients with facial nerve palsy caused by the fracture of the temporal bone, 28 were treated surgically and 8 conservatively. The way of treatment was determined after the detailed radiologic, neurootologic, vestibular and functional hearing examinations as well as of the damaged facial nerve. Numerous neurootologic disorders have the decisive clinical value in evaluation of the site and degree of destruction and selection of adequate way of treatment. The authors have shown that early surgical intervention and combined transmastoid and translabyrinthine approach provide the most suitable conditions for surgical management of the facial nerve and all associated damages in the region of the middle and inner ear. PMID- 8351884 TI - [Therapy of infected pseudarthroses of the lower leg]. AB - The retrospective study comprised 23 patients with infected pseudoarthrosis after osteosynthesis of of the lower log fracture treated at the Clinic of Orthopedic Surgery and Traumatology in Novi Sad. Staphylococcus aureus has been the most common causative agent of infection. In all patients debridment of infection foci was performed and reosteosynthesis with the external fixator and in 10 patients spongioplasty was performed in addition. At the control examination good results were achieved in 4, satisfying in 3 and poor in 16 patients. Amputation was performed in 5 patients. PMID- 8351885 TI - [Infections of the sternum after cardiac surgery]. AB - Methods of treatment of suppurative mediastinitis in cardiosurgical operations applied at the clinic are analysed. These methods are: debridment with closure of the sternum with irrigation of the substernal space, debridment with bandage of open wound and healing per secundam, debridment with bandage of open wound and its closure by myocutaneous layers. It has been concluded that these infections are very complex etiopathogenetically because of which it is very important to know all relevant risk factors aiming to prevent development of this complication in cardiosurgical operations. Its early recognition is necessary. PMID- 8351886 TI - [Carbamazepine cardiotoxicity in acute poisoning]. AB - Manifestations of cardiotoxicity in 9 patients with acute carabamazepine poisoning treated at the Clinic of Toxicology and Clinical Pharmacology of the M.M.A. in 1989 are reported. In all patients together with symptoms and signs characteristic for acute carbamezapine poisoning, there have been also present disorders of the cardiovascular system. The most common clinical signs of cardiotoxicity have been tachycardia and hypotension, and electrocardiographic, ventricular extrasystoles and repolarization disorders. Cardiotoxic manifestations in two cases have been the vital threat for the patients. After application of nonspecific and symptomatic therapy, clinical and electrocardiographic signs of cardiotoxicity were withdrawn, that is, heart sequeles were not recorded. PMID- 8351887 TI - [Chlamydia trachomatis and Reiter's syndrome]. AB - Results of the study of incidence of chlamydia trachomatis infection in patients with Reiters syndrome are presented. Chlamydia trachomatic was isolated from the uretral smear in 12 (34.28%) of 35 patients with Reiter's syndrome. In the group of patients with other rheumatologic diseases Chlamydia trachomatis was isolated in 2 (5.13%) of 39 patients. In all patients with negative isolation, infection was confirmed serologically also and in some patients with negative isolation it was also proved. PMID- 8351888 TI - [Argyrophilic nucleolar organizers in squamous changes in bronchial epithelium]. AB - Argyrophil technique for presentation of interphase nucleolar organiser regions (AgNOR) is becoming an important method in tumour pathology which is used in diagnosis and prognosis. The number of interphase AgNOR is in the strict correlation with the degree of cell proliferation. We have used this technique in evaluation of degree of differentiation and proliferation of squamous changes of the epithelium of the bronchial mucosa. The statistically significant differences were found (p < 0.01) in the number of AgNOR by nucleus in cells of benignant squamous metaplasia (3.31) and epidermoid bronchial carcinoma (5.34). On the basis of numerical values of AgNOR epidermoid bronchial carcinomas could be divided into the group with low proliferative capability (AgNOR < 5.34) and in the group with high degree of proliferation (AgNOR > 5.34). Prognosis of patients with tumours with the high AgNOR value is poorer and they require additional systemic chemotherapy regardless of the clinical state of the disease at the moment of surgical intervention. PMID- 8351889 TI - [Lymphocytoma cutis]. AB - Three patients with skin lymphocytoma and different histologic and clinical appearance of lesions (solitary, grouped, and in the third patient one lesion appeared on the forehead and one on the neck) are presented. By the histologic analysis and the use of immunohistochemical methods the differentiation of these lesions from skin lymphoma and other diseases which could resembe lymphocytoma was made. The method of immunoperoxidase has clearly shown formation of follicules and polyclonal lymphocytes which is the main histologic feature of this pseudolymphoma. By the method of indirect immunofluorescence, antibodies against Borrelia burgorferi were not found in the sera of two patients while in the third it was not performed. PMID- 8351890 TI - [Diagnosis and therapy of lumboischialgia of disk origin]. PMID- 8351891 TI - [The role of the computer in forensic medicine]. PMID- 8351892 TI - [The modern approach to ischemic cerebrovascular diseases--with special emphasis on algorithms for neuroradiologic management]. PMID- 8351893 TI - [Diet and gastric cancer]. PMID- 8351894 TI - [Disorders of olfactory function]. PMID- 8351895 TI - [Neurosurgical experience at the battlefield in Knin]. PMID- 8351896 TI - [Pulmonary alveolar proteinosis]. PMID- 8351898 TI - Sexual misconduct statement of the West Virginia Board of Medicine. PMID- 8351897 TI - How the Health Care Surrogate Act of 1993 will simplify medical care in West Virginia. AB - The West Virginia Health Care Surrogate Act of 1993 became effective July 1, 1993. This law establishes a process for making health care decisions for adults who lack decision-making capacity and who have not completed a medical power of attorney that does not require judicial involvement. The law describes how a health care surrogate is to be selected by the physician, and it provides immunity to the physician and surrogate who make health care decisions according to its provisions. This article presents a case in which the application of the new law is demonstrated. PMID- 8351899 TI - An implication for bone posterity: dietary calcium intake in medical personnel in southern West Virginia. AB - Osteoporosis in the postmenopausal and elderly years is caused by a multitude of factors, which include calcium intake, and is felt largely to be a preventable situation. Low dietary calcium intakes (505 mgs. daily) are common in middle-aged females in southern West Virginia. Further information about the demographic factors in the elderly population from all socioeconomic groups needs to be explored to effect changes in dietary lifestyles. PMID- 8351900 TI - Papillary intraperitoneal neoplasia resembling ovarian carcinoma after removal of benign ovaries. AB - Ovarian cancer continues to be a major cause of death in women since there are no reliable screening methods and because symptoms usually do not appear until the disease has progressed to Stage III or IV, when the chances of cure are very poor. Prophylactic oophorectomy is being considered by some physicians for any woman undergoing hysterectomy after age 40-45. Even with the removal of benign ovaries, intraperitoneal carcinomatosis histologically resembling ovarian cancer can occur. This article describes a case of primary papillary intraperitoneal neoplasia resembling serous adenocarcinoma of the ovary which presented two years after removal of benign ovaries. PMID- 8351901 TI - Report of Pseudomonas aeruginosa sinusitis in a patient with AIDS. AB - Pseudomonas aeruginosa can cause infections in AIDS patients who frequently do not have the usual predisposing conditions such as neutropenia and intravenous drug use. The infections due to P. aeruginosa may be difficult to treat in AIDS patients. Sinusitis has been increasingly recognized as a complication in patients with AIDS. This article describes a case of recurrent P. aeruginosa sinusitis which, until recently, was rarely reported in AIDS. PMID- 8351902 TI - Expanded definition increases number of reported AIDS cases. PMID- 8351903 TI - Carotid endarterectomy for prevention of stroke. AB - Carotid endarterectomy, a frequently performed operation, has been used as a strategy for preventing stroke in patients with carotid bifurcation disease. The safety and efficacy of the operation were recently challenged by a number of sources. Three major responses to this challenge were to retrospectively review the natural history of carotid bifurcation disease compared with the immediate and long-term results of carotid endarterectomy, to initiate 6 prospective randomized trials to determine the efficacy of carotid endarterectomy for a variety of indications, and to develop appropriateness initiatives and guidelines for using this surgical procedure by organizations concerned with health care policy. I review the current status of these 3 areas of endeavor. In those areas where studies are complete, carotid endarterectomy has been shown to be highly effective in reducing stroke risk. Risk reduction has ranged from 66% to 80% compared with medical management. Based on these sources and findings, I present a list of indications for the operation for surgeons who are able to do the operation safely and within the guidelines established by the Stroke Council of the American Heart Association. PMID- 8351904 TI - Misunderstanding in the classification of diabetes mellitus. What's in a name? AB - To assess whether physicians, residents, medical students, hospital diagnosis coders, and patients properly use the designations insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) that were established by criteria of the National Diabetes Data Group, we reviewed clinic and hospital records and administered questionnaires. Although essentially all cases of true IDDM were identified as such and most cases of NIDDM not requiring insulin therapy were correctly identified by all groups, patients with NIDDM on insulin therapy were misidentified as having IDDM by 38% of residents in internal medicine clinics and 68% of primary care and surgical subspecialty residents. On a survey, of 22 patients with NIDDM on insulin therapy, 17 (77%) considered themselves to have IDDM. Thus, patients who have NIDDM by the established criteria who are on insulin therapy are commonly mislabeled as having IDDM. We present an approach for dealing with this problem by adapting nomenclature focusing on insulin deficiency and resistance. It would probably also be helpful to separately identify the subset of patients with "insulin-deficient diabetes" who are ketosis-prone. It is important to use immunologic profiling (islet cell antibody testing) and insulin sensitivity or deficiency testing (C-peptide levels). PMID- 8351905 TI - Rehabilitation services for the Pacific. AB - The Pacific Basin Rehabilitation Research and Training Center was created to help meet the challenges of rehabilitating people in rural remote communities in the United States-associated Pacific. We describe the center, the special region it serves, some of its many programs, and some of the ways it is helping communities in this region provide services that are appropriate and sensitive to the culture, the environment, and the disability. PMID- 8351906 TI - Neuroplasticity. Key to recovery after central nervous system injury. AB - After an injury to the central nervous system, physical and cognitive impairments and disabilities often abate. These gains may be partly mediated by mechanisms that allow reorganizing of the structure and function within gray and white matter. The potential to enhance neurologic recovery by manipulating the brain and spinal cord must now be considered in clinical practice. Today's rehabilitation routines may not encourage maximum recovery. Indeed, some commonly used physical and pharmacologic methods could inhibit the restoration of motor activities such as walking. On the other hand, therapies that use our expanding knowledge of neuroplasticity could lead to better results for patients. PMID- 8351907 TI - Evaluating chest pain in the emergency department. AB - Chest pain is one of the most difficult diagnostic problems for physicians working in an emergency department. In this setting, more malpractice dollars are awarded for missed myocardial infarction than for any other physician error. This problem usually occurs when the patient has atypical symptoms, the physician is inexperienced, or the diagnosis is not considered. The clinical manifestations of myocardial infarction vary greatly, and patients with "atypical" presentations have a poorer prognosis than those with classic symptoms. Although no feature of a patient's history excludes infarction with certainty, pain that is sharp, positional, pleuritic, or reproduced by palpation indicates a lower probability of acute ischemic heart disease. New immunochemical methods and serial sampling strategies have increased the sensitivity of creatine kinase-MB as an indicator for the disorder. Recent investigations have also established the prognostic value of the initial electrocardiogram. These methods allow emergency physicians to assess the risk of complications and to perform triage when there is a shortage of beds in the coronary care unit. Emergency physicians must also consider other diseases for which coronary care might be beneficial. PMID- 8351909 TI - Treatment of laryngeal dysphonias. PMID- 8351908 TI - Magnetic resonance imaging-guided needle biopsy of head and neck lesions. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in otolaryngology-head and neck surgery. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in otolaryngology-head and neck surgery that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Otolaryngology-Head and Neck Surgery of the California Medical Association, and the summaries were prepared under its direction. PMID- 8351910 TI - Management of the internal carotid artery in skull base operations. PMID- 8351911 TI - Olfactory impairment. PMID- 8351912 TI - Positron emission tomographic imaging of the head and neck. PMID- 8351913 TI - Microvascular free flaps in head and neck reconstruction. PMID- 8351914 TI - Spasmodic dysphonia and laryngeal botulinum toxin injection. PMID- 8351915 TI - Endoscopic sinus surgery. PMID- 8351916 TI - Rat-bite leptospirosis. PMID- 8351917 TI - Accidental poisoning by warfarin-contaminated herbal tea. PMID- 8351918 TI - Benefits of stopping smoking. AB - This article launches a special WESTERN JOURNAL OF MEDICINE effort to help prevent disease and disability. Erica Frank, MD, MPH, an Assistant Professor in the Department of Community and Preventive Medicine and Department of Medicine, Emory University School of Medicine, and Adjunct Professor at the Emory University School of Public Health, Atlanta, Georgia, will head the endeavor. The goals are to present scientific foundations for prevention and to provide practical ways to improve patients' lives. This first article addresses smoking cessation. We may think that we know it all, but we may not, and patients do not: about 25% of Americans smoke, and more than half of persons who ever smoked began their fatal habit before they were 18 years old. Side-stream smoke affects adults and children adversely, too, causing inflammation, infection, and cancer. Smokers need to stop smoking, and young people need to not start. Dr Frank's review is accompanied by a page for patients. It debunks myths and is designed to be duplicated so patients can leave their physician's office with a new lease on life in hand. Look for future prevention-oriented articles in this series that feature science and patient education. PMID- 8351919 TI - Health decisions movement. PMID- 8351920 TI - Carotid endarterectomy--the big picture. PMID- 8351921 TI - A scientific basis for neurologic rehabilitation. PMID- 8351922 TI - Earthquakes and myocardial ischemia. PMID- 8351923 TI - High tech in a low tech country. PMID- 8351924 TI - An offshore pharmacy--a bargain or a danger? PMID- 8351925 TI - Testing cardiac function. PMID- 8351926 TI - [Renovascular hypertension: invasive percutaneous diagnosis and therapeutic possibilities]. AB - Under the current conditions of improved pharmacological therapy of arterial hypertension there is a danger that the physician may overlook considering the possibility of underlying renovascular causes for the hypertension. However, the diagnosis and treatment of these conditions are simple and easily accessible. Digital subtraction angiography is a simple technique which enables the diagnosis of renal artery stenosis or stenosis of the aorta to be made as a cause of hypertension in more than 90% of cases. Dependent on the type, extent and location of obliteration in the renal arteries, percutaneous transluminal-renal dilatation with a balloon-catheter is quite frequently the intervention of choice. In fibromuscular dysplasia the results are excellent, with a cure rate exceeding 90%, the patients being predominantly younger and females dominating. In stenosis of atherosclerotic origin, 40-60% show improvement or even normalization of blood pressure. A sudden recurrent increase in blood pressure during long-term follow-up requires angiography in order to perform either dilatation again or surgical reconstruction. In all cases of renovascular hypertension, interdisciplinary cooperation between surgeons and interventional radiologists is essential and all patients with renal insufficiency require close contact to a dialysis centre. PMID- 8351927 TI - [Reducing blood pressure and modification of coronary risk factors by therapy with doxazosin]. AB - In an open, non-comparative, multicenter trail performed by general practitioners, the efficacy and safety of doxazosin, an inhibitor of postsynaptic alpha 1-adrenoceptors, were studied in 924 patients with mild to moderate hypertension. Under treatment with doxazosin both systolic and diastolic blood pressure decreased significantly from 178.4 +/- 18.2/103.1 +/- 8.6 to 149.1 +/- 12.0/85.6 +/- 7.3 mm Hg; the mean daily dose at the end of the 12 weeks' treatment period was 3.3 +/- 2.6 mg. Heart rate decreased by 5% and body weight by 6%. As compared with baseline values, total cholesterol (255.7 +/- 45.4 vs 232.7 +/- 37.3 mg%), triglycerides (206.3 +/- 97.6 vs 175.2 +/- 70.9 mg%) and blood glucose (101.9 +/- 31.0 vs 97.9 +/- 25.5 mg%) decreased significantly, whilst HDL-cholesterol (47.7 +/- 13.0 vs 51.5 +/- 12.4 mg%) increased. Overall, doxazosin was very well tolerated; only 16% of all patients reported adverse drug reactions. The results of this study confirm the effectiveness of doxazosin as first-line medication in the treatment of hypertension, especially in patients with concomitant metabolic disorders such as hyperlipidemia and diabetes mellitus. Moreover, the patients who appear to benefit most from doxazosin treatment are those who show the highest metabolism-related coronary risk, as calculated according to the Framingham Study equation. PMID- 8351928 TI - [Allergic rhinitis, respiratory obstruction and bronchial asthma in the Vienna population]. AB - In the present study the incidence of bronchial asthma, airway complaints, and allergic rhinitis was investigated in a randomized population section including 3000 male and female inhabitants of Vienna (sex ratio 1:1), aged 20-44. Data on complaints in the respiratory tract were obtained from a total of 71% of the study population. Our results suggest that 14.7% of the entire population was suffering from allergic rhinitis (16.4% male versus 13.0% female; p < 0.05). Airway complaints such as wheezing, whistling, and feeling of tightness in the chest, awakening because of shortness of breath or cough were frequently reported, with no major differences between male and female subjects. The overall percentage of study subjects stating that they had suffered from airway complaints in the year before, i.e., the percentage of those giving affirmative answers to one of the questions, was 29%. Bronchial asthma was calculated to be present in 5.1% of the entire population (5.9 male versus 4.4 female). Attacks of asthma were reported by only 2.2% of the subjects, which gives an indication of the discrepancy between identified and unidentified bronchial asthma. Allergic rhinitis is correlated to, and constitutes a risk factor for the occurrence of complaints in the respiratory tract; public health policy should therefore be aimed at the prevention or early treatment of allergic rhinitis, and at reducing the proportion of cases suffering from unidentified bronchial asthma. PMID- 8351929 TI - [Accuracy of blood glucose self-monitoring in children with type-I diabetes]. AB - Children with type I diabetes often believe that they are able do gauge their blood glucose value without measurement. This study investigated how accurate these estimates are and which of the patient characteristics might affect accuracy. Nineteen children with type I diabetes (age 7.3-17.3 years, duration of diabetes 0.1-12.0 years) estimated their blood glucose immediately before a blood glucose measurement by reflectance meter. Ten to 54 estimations and measurements were done by each individual during a summer camp. According to the method of Cox et al. accuracy of estimates was evaluated by error grid analysis. Five zones were defined: accurate estimates (zone A); clinically benign errors (zone B); clinically dangerous errors (zone C, D, E). An overall accuracy index was calculated by subtracting the summed percentage of estimates in zones C, D, E from the percentage in zone A. The mean percentage of estimates in zone A was 41.5 (10.0-75.0)%, the mean overall accuracy index was 9.8 (-47.4-62.5)%. Except for mean blood glucose which was inversely correlated with accuracy index (r = 0.53, P = 0.02) none of the other patient characteristics showed an effect on accuracy index. CONCLUSIONS: Accuracy of blood glucose estimates is lower in children with type I diabetes than in adults and varies substantially between individuals. High mean blood glucose values are associated with a lower accuracy of estimates. PMID- 8351931 TI - [Help for the elderly and rehabilitation of the elderly in inpatient treatment- experiences from a nursing home (nursing care facility)]. PMID- 8351930 TI - [Rehabilitation for the elderly, why?]. AB - Within human culture the attitude towards the aged has been very different up to now, ranking from ritual slaughter to worshipping of the wise old persons. Ambivalence persists till now. We have introduced the terminus "rehabilitation of the old" to indicate a principal which is adequate in the medical sense as it is adequate to humanity. Our slogan runs: nursing alone (meaning isolated care for vegetative necessities) is inhuman in old people. Rehabilitative view points and activities must come into the care for the aged on all levels there are: from readaptation to profession, "over independence and being socially adequate" up to the resting last possibility of having fun. Rehabilitation of the old can only succeed if there is an integrative set up which means (again as a slogan): We want rehabilitation of old to invade all hospitals and all human groupements instead of bringing the old out of these groupings and separate them in senior ghettos. This must go hand in hand with specialization and scientific identification of geriatrics and rehabilitation; specially neuro-rehabilitation and rehabilitation of the old, which are in close connex. Quite a number of administrative barriers have to be removed, new possibilities must be created. There must be a complete new viewing of the matter and new goals in medical education, as well pregraduate as postgraduate. A new generation of doctors can find here a big good chance. However, it can only be successful in close collaboration with a progressive politic administration. PMID- 8351932 TI - [Elderly patients in internal medicine departments]. PMID- 8351933 TI - [Nursing personnel--responsibilities and problems within the scope of rehabilitation of the elderly]. PMID- 8351934 TI - [Rehabilitation--rehabilitation of the elderly: basic concepts and their implementation]. PMID- 8351935 TI - [Discussion and summary of the first inquiry into "rehabilitation of the elderly"]. AB - Financial amelioration is important but not the only important. We need a better prestige of rehabilitation of old age in society and in science. We need a better motivation. Last but not least permanent accompanying standardization and evaluation. Better schooling and post graduate education has to take place within all degrees of health professions, mainly in doctors and other leading people, eventually "obligatory". We want no "ghettos for aged" which means purely geriatric wards. A modern human (as well scientifically as sociologically appropriate) way is to have mixed populations in the wards. Modern concept should include more phantasy, more individualism instead of standardization. We want new trends not only in scientific thinking but as well and even more in political and social thinking towards these goals. PMID- 8351936 TI - [Psychotropic drugs outside of psychiatry, especially in advanced age]. AB - The following main rules will optimate use of psychopharmaca: 1) The 3 main groups of psychopharmaca have to be ordered according to clear cut target symptoms: tranquilizer, neuroleptics, antidepressants. 2) Dosage must be rational and individual. Administration has to be long enough (antidepressants) and short enough (tranquilizers) according to chemical group, to secure efficacy and to avoid addiction. 3) The 2 polar dimensions: more agitating and more tireding, have to be used deliberately. 4) Danger of drug addiction and other unfavourable side effects must be kept in mind. PMID- 8351937 TI - Rehabilitation after cardiovascular diseases, with special emphasis on developing countries. Report of a WHO Expert Committee. PMID- 8351938 TI - [Importance of echocardiography in general clinical routine practice]. AB - Echocardiography was carried out in 526 patients on a general internal medical ward, 54.8% with a clinical indication and 45.2% in screening. The results were compared with the data from the scout view chest x-ray and from the ECG. Enlargement of the cardiac cavities detected in echocardiography (UCG) can only be found in 43% in the x-rays (left atrium 27%, left ventricle 64%, right ventricle 42%). Left ventricular hypertrophy was shown in the UCG in 43% of patients with arterial hypertension: of these, 28% had a pathologic ECG. On the other hand, only 14% of all hypertensive patients show signs of left ventricular hypertrophy on x-ray. The differentiation of systolic (44%) and diastolic (38%) dysfunction was only possible by means of UCG in congestive heart failure. A chronic pulmonary hypertension detected by x-ray correlated with an enlargement of the right ventricle in the UCG. UCG is indicated when there are clinical, ECG, chest x-ray signs of heart disease, arterial hypertension or chronic pulmonary hypertension. UCG is not a screening method. PMID- 8351939 TI - [Quantitative evaluation of aortic valve insufficiency in magnetic resonance tomography]. AB - Flow-encoded magnetic resonance (MR) sequences allow the quantitative evaluation of blood flow in any plane of the heart and vessels. For the first time, ejection and regurgitation volumes of the left ventricle in the ascending aorta can be measured noninvasively. Thus, the regurgitation fraction as a reliable measure of aortic valve insufficiency can be determined. The quantitative evaluation of aortic valve insufficiency was done by MR in comparison to ultrasound-Doppler and, in some cases, in comparison to heart catheterization. A good correlation of grading aortic valve insufficiency by the new MR-technique in comparison to clinical graduation is shown. The development of a new noninvasive standard for quantification of aortic valve insufficiency seems possible. PMID- 8351940 TI - [Intra-individual reproducibility of tilt table studies in diagnosis of vasovagal syncope]. AB - Neurally-induced syncope appears to be the underlying pathophysiologic mechanism in many patients with unexplained syncope. Diagnosis of vasovagal syncope, however, remains difficult and constitutes in many cases an exclusion diagnosis. The present study thus aimed to determine the yield of tilt-table testing in the work-up of patients with unexplained syncope and most importantly to examine the reproducibility of the results of this method. Twenty-four patients with a history of syncope and 11 healthy volunteers were examined on 2 days. In 10 patients, symptoms could be provoked during tilting, in 8 during both tests, in 2 only on one occasion. Only 1 of 11 volunteers developed presyncope during tilting which was not reproducible during the second test. These findings resulted in a sensitivity of 42% and a specificity of 91% for the protocol employed in this study. Overall reproducibility was 91% which suggests that this tilt-table protocol is suitable for evaluation of therapeutic interventions in patients with neurally-mediated syncope. PMID- 8351941 TI - [Shortening the stimulus T time: indicator for physical activity in patients with demand modulated cardiac pacemakers]. AB - Activity-modulated pacemakers detect body vibrations and increase their pacing rate. As the body vibrations are not always related to physical activity, we studied in 20 patients with the activity-modulated pacemaker Legend (Medtronic) whether a second physiological signal, the paced QT duration, can help to verify exercise. At rest, pacing rate was programmed from 60 ppm to 130 ppm in steps of 10 ppm which shortened the QT duration from 467 +/- 32 ms (60 ppm) to 391 +/- 24 ms (130 ppm). During treadmill exercise, pacing rate increased from 62 +/- 1 ppm to 98 +/- 9 ppm and the QT duration decreased from 450 +/- 25 ms to 372 +/- 27 ms. Compared to rest, the exercise-induced QT shortening was significantly shorter for pacing rates > or = 70 ppm. To simulate artificial sensor activation, an electrical razor was put onto the pulse generator. Pacing rate increased to 81 +/- 7 ppm, but the QT duration shortening was similar to the measurement at rest with 80 ppm. In conclusion, the paced QT duration is able to confirm whether body vibrations are related to physical exercise. PMID- 8351942 TI - [Cardiac characteristics of patients with terminal renal failure after kidney transplantation]. AB - Left ventricular (LV) hypertrophy and dysfunction are risk factors for high mortality from cardiovascular causes in patients with end-stage renal disease. To determine the frequency of these findings after kidney transplantation, 45 patients (11 female, 34 male; age: 47.2 +/- 12 years) after transplantation (57 +/- 37 months) with (n = 21) and without (n = 24) a patent arteriovenous fistula were analyzed with echocardiography. A high prevalence of systolic (> 140 mm Hg: 40%) and diastolic (> 90 mm Hg: 18%) hypertension was observed despite the use of 1.44 +/- 0.9 (range: 0-3) antihypertensive drugs per patient. Most frequent echocardiographic findings were LV hypertrophy (78%; LV mass = 318 +/- 81 g), mostly in the asymmetric septal form (47%; mean ratio septal/posterior wall thicknesses: 1.38 +/- 0.2), and left atrial dilatation (60%; mean diameter: 44 +/ 6 mm). LV dilatation (33%; mean enddiastolic diameter: 53 +/- 5 mm) and systolic dysfunction (20%; mean ejection fraction: 64 +/- 11%) were less common. Individual values of LV mass were directly correlated with systolic blood pressure (p < 0.05). No relation was found between other echocardiographic (LV and left atrial diameters, LV mass, ejection fraction or velocity of circumferential fibre shortening) and clinical (transplantation duration, serum hemoglobin or creatinine, patency of dialysis access, or choice of immunosuppressive therapy) parameters. The presented data suggest that LV hypertrophy is frequent after renal transplantation, and that arterial hypertension is a key factor for the maintenance of LV hypertrophy in these patients, while the patency of the dialysis access, and the durations of transplantation or of preceding dialysis therapy are not relevant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351943 TI - [Atrial arrhythmias after modified Fontane operation: effect of preoperative hemodynamics and the kind of operation (atriopulmonary vs. total cavopulmonary anastomosis)]. AB - Between October 1986 and March 1992, occurrence of supraventricular tachycardia and sinus node dysfunction was investigated pre- and postoperatively by serial ECG and Holter monitors in 63 consecutive patients with univentricular circulation after modified Fontan operation (total cavopulmonary connection 39 patients, atriopulmonary connection 24 patients). Mean age at operation was 7.2 (0.1-20.3) years. Of the 63 patients, 14 (22%) had early (< 14 d) supraventricular tachycardia or sinus node dysfunction, which was not related to the type of operation. None of nine patients with a preoperative mean right atrial pressure < or = 2.5 mm Hg had early supraventricular tachycardia or sinus node dysfunction, in contrast to 16/54 patients (30%) with a preoperative mean right atrial pressure > or = 2.5 mm Hg. 6/63 patients died during the early (< 14 d) postoperative period. In only one child death was related to a dysrhythmia (junctional ectopic tachycardia). During a mean follow-up of 2.5 years, 12 patients (21%) had late supraventricular tachycardia or sinus node dysfunction. Early supraventricular tachycardia/sinus node dysfunction was a predictor of late atrial dysrhythmias, as it occurred in eight of the surviving 14 patients with early dysrhythmias, in contrast to four children without early atrial dysrhythmias (p < 0.001). After creation of an atriopulmonary connection, 10/22 patients (45%) had late supraventricular tachycardia/sinus node dysfunction, but only 2/35 patients (6%) with a total cavopulmonary connection had late atrial dysrhythmias (p < 0.001). CONCLUSIONS: Early atrial dysrhythmias after the Fontan operation were related to preoperative hemodynamics. Early supraventricular tachycardia/sinus node dysfunction and the atriopulmonary type of Fontan connection were significant risk factors for late atrial dysrhythmias. PMID- 8351944 TI - [Therapy of postoperative ectopic junctional tachycardia by surface hypothermia]. AB - Postoperative junctional ectopic tachycardia is associated with a poor prognosis in patients after open-heart surgery. This dysrhythmia has been shown to be resistant to medical treatment as well as to epicardial pacing and external cardioversion. Successful therapy with surface hypothermia in an infant with junctional ectopic tachycardia (ventricular rate 210-230 bpm) after repair of tetralogy of Fallot is presented. Hypothermia (rectal temperature 32-34 degrees C) was effective in decreasing the ventricular rate of the dysrhythmia (< 170 bpm). After spontaneous cessation of the tachycardia, sinus rhythm resumed, resulting in stable hemodynamics. PMID- 8351945 TI - [Pulmonary edema as a complication during pericardial puncture in "mixed connective tissue disease"]. AB - A 22-year-old female patient with an 8-year history of mixed connective tissue disease (systemic sclerosis overlapping with systemic lupus erythematosus) presented with marked respiratory distress, sinus tachycardia (135 bpm), and pulsus paradoxus. The chest x-ray showed an enlargement of the cardiac silhouette, which was due to a 3-cm-wide, circular pericardial effusion, as demonstrated by two-dimensional echocardiography. Pericardiocentesis performed to decompress cardiac tamponade did not lead to clinical improvement. The increase in dyspnea was caused by a rise in pulmonary wedge pressure from 21 to 40 mm Hg following an acute increase of mitral valve regurgitation. In the presence of global hypokinesia of the left ventricle, cardiac output decreased from 3.25 to 2.63 l/min. Intensive care including hemodialysis and plasmapheresis as well as high-dose application of cyclophosphamide and steroids led to a stabilization of the hemodynamic situation over a period of days. The case report presented here supports the general recommendation to perform pericardiocentesis in a stepwise manner under hemodynamic monitoring. This holds true primarily for patients with mitral valve regurgitation and/or cardiac involvement in connection with an underlying disease. PMID- 8351946 TI - [Treatment of acute pulmonary hemorrhage in a patient with pulmonary atresia and ventricular septal defect by coil embolization of a systemico-pulmonary collateral artery]. AB - Pulmonary hemorrhage due to rupture of pulmonary arteries causes significant morbidity and mortality in the natural history of older patients with pulmonary atresia and ventricular septal defect. The only therapeutical option for patients with persisting pulmonary hemorrhage was surgical resection of the involved pulmonary segments. In this case report we describe the successful termination of an acute pulmonary hemorrhage in a 9-year-old patient by coil-embolization of a systemicopulmonary collateral artery, which provided additional blood supply to the left upper-lobe segments. The hemorrhage ceased within 24 h and has not recurred during a follow-up period of 7 months. In our opinion, the success of the embolization can be attributed to a reduction of the perfusion pressure and a normalization of the arterial blood flow in the affected lung segments. PMID- 8351947 TI - [Reversible contact lesion in mitral valve endocarditis--follow-up study with transesophageal echocardiography]. AB - This is a case report of a 59-year-old patient with an endocarditis of the mitral valve caused by streptococcus viridans. Precordial echocardiography showed a highly mobile vegetation of the anterior mitral leaflet prolapsing during systole into the left atrium. During diastole contact with the ventricular septum caudally to the left ventricular outflow tract was noted. By using transesophageal echocardiography (TEE), this zone appeared as a localized increased echogenity of the parietal endocardium and underlying myocardium. Antibiotic therapy led to a cure of the endocarditis (clinically and according to clinical chemistry). The TEE follow-up 2 months later showed persisting mitral valve vegetation, whereas neither the endocardial lesion nor the abnormal myocardial echo pattern were seen any longer. The likely inflammatory etiology of the described lesion is discussed and seems obvious. PMID- 8351948 TI - [Psychotropic effects of Sino-Japanese traditional medicines]. AB - Recently there are a number of clinical reports that Sino-Japanese traditional medicines have good effects on patients with anxiety and/or depression. To detect the clinical efficacy of those medicines, we have examined those effects on various behavioral changes induced by stress in experimental animals. Although it appears to be possible to demonstrate a part of the psychotropic effects of the medicines, their action mechanisms are far from being understood. An improving effect of Shimotsu-to on the spatial cognitive deficits induced by scopolamine in eight radial maze might be due to that of paeony root and to its major principle, paeoniflorin. However, it appears that pharmacological effects of Shimotsu-to, a traditional medicine, cannot be explained by those of an active principle of paeony root, paeoniflorin. PMID- 8351949 TI - [On the fluctuation of plasma biopterin levels for 24 h in normal controls]. AB - Tetrahydrobiopterin (BPH4) is the cofactor for the pteridine-dependent monooxygenases, which play important roles in the biosynthesis of cateholamines and indolamines. These biogenic amines have been thought to be related to affective disorders, and the increase of total biopterin (BP) and the lower ratio of BPH4 to total BP were observed in plasma of patients with affective disorders. For the purpose of giving an explanation of these changes of plasma biopterin mentioned above in patients with affective disorders, the fluctuation of plasma biopterin levels for 24 h was measured by high-performance liquid chromatography with fluorescence detection by the method of Fukushima and Nixon in ten normal volunteers. The total BP and BPH4 levels in plasma at 9 am were the highest, and those levels at 1 am were the lowest. The range of the fluctuation of total BP with the passage of time was narrow compared with the range of the increase of total BP observed in the patients with affective disorders. Other factors in addition to the fluctuation of plasma BP for 24 h were thought to be related to the changes of plarma BP levels in the patients with affective disorders. PMID- 8351950 TI - [Impairment of learning and memory and the accessory symptom in aged rats as senile dementia model (1)--Emotional behavior]. AB - It is well known that there is an increase of emotional behavior in senile dementia. There are few studies investigating age-related emotional behavior. We attempted to investigate emotional behavior of aged rats using various tests. Locomotor activity for 24 h decreased in aged rats compared with that in young rats. There was no difference in locomotor activity between light and dark periods in aged rats. There was no visual abnormality on light/dark discrimination test in aged rats. It suggests that locomotor activity during dark period may be impaired by aging. Head-dips and social interaction time in hole board and social interaction tests, respectively decreased, while start latency, defecation and urination in open field test increased in aged rats. Furthermore, ambulation and rearing in hole board, social interaction and open field tests decreased, and entries into open or closed arms in elevated plus-maze test reduced in aged rats compared with those in young rats. These findings suggest that anxiety may increase, but spontaneous activity decrease in aged rats. These results indicate that aged rats may be useful as an accessory symptom model of senile dementia. PMID- 8351951 TI - [Impairment of learning and memory and the accessory symptom in aged rats as senile dementia model (2)--Learning and memory]. AB - We attempted to investigate the ability of learning and memory of aged rats. Swimming speed of aged rats in Morris's water maze was slower compared with that of young rats. Therefore, we used goal distance to indicate ability of learning and memory. In training session, distance for both groups decreased with training, but in aged rats it was significantly longer than that in young rats. In retention test 24 d after the training, distance in aged rats was longer than that in young rats, although there was no difference in distance for both groups between acquisition and retention tests. The distance in the working memory tended to increase with aging. There was no difference in time spent within platform phase in probe trial, in percent movement of first trial in habituation test, and in step-through latency in passive avoidance, between young and aged rats. Drinking latency for aged rats in water finding task was significantly longer compared with that in young rats. These findings suggest that learning and memory were impaired by aging in spatial and latent learning tasks. Aged rats could acquire and maintain memory of simple tasks, but in spatial tasks they tended to show decreased ability of retention and working memory. PMID- 8351952 TI - [The effect of CRF antagonist on immobilization stress-induced increases in noradrenaline release in rat brain regions]. AB - We investigated the effects of intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) antagonist, alpha-helical CRF9-41 (ahCRF) on stress-induced increases in noradrenaline (NA) release in rat brain regions. Pretreatment with ahCRF (50 or 100 micrograms) attenuated significantly the stress-induced increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of NA in rat brain, in the locus coeruleus region, cerebral cortex, hippocampus, amygdala and hypothalamus. Plasma corticosterone levels were not decreased significantly by administration of ahCRF. From these results, it is suggested that stress-induced increases in NA release in the rat brain regions are attenuated by ahCRF and thus that CRF, released during the stress, cause increases in NA release in these regions. PMID- 8351953 TI - Human chorionic gonadotropin binding sites in the human endometrium. AB - The existence of high-affinity and low-capacity specific binding sites for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) has been reported in porcine, rabbit and rat uteri. We have identified hCG binding sites in the human endometrium collected from 35-42-year-old ovulatory and anovulatory women. The binding characteristics of hCG to endometrial tissue preparations from ovulatory and anovulatory women showed saturability with high affinity and low capacity. Scatchard plot analysis showed the dissociation constant of specific binding sites in the ovulatory women to be 3.5 x 10(-10) mol/l and in anovulatory women to be 3.1 x 10(-10) mol/l. The maximum binding capacity varied considerably between ovulatory (3.85 nmol/kg protein) and anovulatory (6.12 nmol/kg protein) endometrium. Among the divalent metal ions tested (Zn2+, Mg2+, Mn2+, Ca(2+)--4 mol/l), Zn2+ effected a remarkable increase in [125I]hCG binding to the endometrium (p < 0.005) whereas Mn2+ showed a marginal increase and other metal ions did not have any effect. Data obtained with human endometrium indicate an influence of the functional state of the ovary on [125I]hCG binding to endometrium. PMID- 8351954 TI - Heterologous humoral immune response in patients treated with human growth hormone from different sources. AB - The existence of homologous anti-human growth hormone (anti-hGH) and heterologous anti-bovine growth hormone (anti-bGH) humoral immune responses in hypopituitary patients under hGH therapy has been reported previously. In order to study the influence of the hormone source, both responses were compared by radiobinding assays performed with [125I]hGH or [125I]bGH as tracers. Fifty-seven hypopituitary patients treated with extractive hGH, recombinant methionyl hGH or authentic recombinant hGH were studied. A very low incidence of heterologous antibodies was found in patients under recombinant hGH therapy, contrary to the high incidence observed in patients treated with extractive hGH preparations. In addition, immunochemical studies performed with a synthetic peptide (hGH 44-128) indicated that this peptide exhibited, in the anti-bGH/[125]bGH radioimmunoassay system, higher reactivity than the native hGH, suggesting that such a fragment resembled an altered conformation of the hormone. The high heterologous response elicited only by the extractive hGH along with the behaviour of the hGH 44-128 fragment supports the fact that the extraction and purification procedures in extractive preparations may alter slightly the structure of the hGH molecule and trigger a heterologous immune response. PMID- 8351955 TI - Microsomal antibodies during gestation in relation to postpartum thyroid dysfunction and depression. AB - RATIONALE: Microsomal antibodies have been related to postpartum thyroid dysfunction and postpartum depression. OBJECTIVES: To detect the value of microsomal antibodies during gestation in a random population, as a risk factor for thyroid dysfunction and depression during the postpartum period. MAIN FINDINGS: The presence of microsomal antibodies was investigated in a random population of 293 women at 32 weeks' gestation. At the same time, postpartum thyroid function was assessed repeatedly in all women every six weeks up to 34 weeks' postpartum. Postpartum thyroid dysfunction, defined as the presence of abnormal TSH, in combination with abnormal fT4 and/or fT3 values, occurred in 21 women (7.2%) during the postpartum period. Depression was assessed using the Research Diagnostic Criteria without knowing the results of biochemical thyroid function tests. At 32 weeks' gestation there were 27 (9.2%) women with elevated microsomal antibody titres. Compared with microsomal-antibody negative women at 32 weeks' gestation, these women had an RR of 20 for developing postpartum thyroid dysfunction and an RR of 1.7 for developing postpartum depression. CONCLUSIONS: Women with elevated microsomal antibody titres during gestation are particularly at risk for postpartum thyroid dysfunction, but only have a slightly increased risk for postpartum depression. PMID- 8351956 TI - Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies. AB - Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown to induce thyroid dysfunction in some cancer patients. The purpose of the present study was to evaluate the incidence and risk factors of this adverse autoimmune response. Triiodothyronine, thyroxine and thyrotropin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopathy (69 patients); rIL-2 was administered intravenously in 5-day cycles (18 x 10(6)-24 x 10(6) IU.m-2.day-1) either alone in 79 cases or in combination with autologous bone marrow transplantation in 26 cases, with interferon-gamma in 37 cases, with tumor necrosis factor-alpha in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was present upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9%) patients exhibited peripheral hypothyroidism, out of which four exhibited biphasic thyroiditis. Another five (3.4%) patients developed transient hyperthyroidism. Anomaly could not be classified in three patients. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abnormalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoimmune antibodies. Antithyroid antibodies were detected in 60.9% of patients with this complication. Thyroid stimulating antibodies were never detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351957 TI - Normal calcitonin response to pentagastrin stimulation in patients with chronic renal failure. AB - High calcitonin levels have been reported in chronic renal failure. To study the C cell response in patients with chronic renal failure, an intravenous bolus of pentagastrin was administered to 11 patients and 11 healthy subjects. Samples were obtained at 0, 1, 2, 3, 5 and 10 min for calcitonin assay. In order to detect only the active monomeric calcitonin, an immunoradiometric assay method was used. The influence of calcium, phosphate, alkaline phosphatase and intact parathyroid hormone was also evaluated. Although basal calcitonin levels were higher (p < 0.01) in chronic renal failure (mean +/- SEM: 10.1 +/- 2.9 pmol/l) versus healthy subjects (1.1 +/- 0.3 pmol/l), the area under the curve showed there to be no differences between the two groups. The rising branch of the area under the curve, employed as an expression of the C cell response capacity, showed no differences either (chronic renal failure vs healthy subjects: 5.6 +/- 2 vs 2.6 +/- 0.7 pmol l-1 min-1, p = 0.28). In the chronic renal failure group, a positive correlation was found (r = 0.625, p < 0.05) between the rising branch of the area under the curve and parathyroid hormone. We conclude that monomeric calcitonin is increased in chronic renal failure, but C cells of the thyroid respond to pentagastrin, as they do in normal subjects. This finding is of great clinical importance when a patient with renal impairment is evaluated for medullary thyroid carcinoma. The calcitonin response to pentagastrin seems to be related directly to the degree of secondary hyperparathyroidism in chronic renal failure. PMID- 8351958 TI - Effects of chronic heroin abuse on bone and mineral metabolism. AB - Though the chronic use of opiates can modify several body functions, only a few data are available on the effects of opioid drugs on mineral metabolism. We have examined the possible consequences of chronic opiate abuse on bone mass, bone turnover and calcium metabolism in 13 male chronic heroin users, examined 1-2 days after the last administration of the drug (group A), 14 former male heroin addicts, examined 4-24 months after drug discontinuation (group B), and 22 healthy, age- and sex-matched control subjects. In group A, the vertebral bone mineral density (measured by Dual-Photon Absorptiometry) was significantly lower (p < 0.05) than in the control subjects, despite similar values of total body bone mineral, lean body and fat mass. Blood-ionised calcium and urinary calcium and hydroxyproline were significantly increased (p < 0.01), whereas parathyroid hormone was lower than in controls (p < 0.01). Bone alkaline phosphatase and osteocalcin, however, were not significantly different from the control values. LH and testosterone levels were low (p < 0.01 vs controls). In contrast, group B subjects did not show significant differences from the control group. The chronic abuse of opioid drugs may be associated with altered bone metabolism and reduced trabecular bone mass, attributable, at least in part, to gonadal deficiency. These alterations seem reversible after drug discontinuation. PMID- 8351959 TI - Effects of cyclosporin A and verapamil on mouse pancreatic islets. AB - Treatment of NMRI mice with cyclosporin A (25 mg/kg body wt) for 11 days caused a marked fall in pancreas insulin content, although plasma glucose and plasma insulin were unchanged. When islets from untreated mice were exposed to cyclosporin A (2 mg/l) in vitro, no effect was seen in the first hour. After 24 h, cyclosporin A had significantly decreased the islet content of insulin. Post culture microperifusion showed that cyclosporin A for 24 or 72 h inhibited the insulin secretory responsiveness. Verapamil in vivo (0.4 mg/kg body wt per day) or in vitro (37.5 micrograms/l) did not modify these effects. Verapamil at 25 mg/l suppressed the release of insulin but afforded no obvious protection against cyclosporin A during culture. The beneficial action of verapamil on islets transplanted to the kidney may reflect renal events rather than a primary interaction of drugs in the islets. PMID- 8351960 TI - Kinetic changes of melatonin release in rat pineal perifusions at different circadian stages. Effects of corticosteroids. AB - The kinetic characteristics of melatonin release were documented in perifused pineal glands removed from rats sacrificed at six circadian stages (light/dark = 12:12): three during the light phase, i.e. 3, 7 and 11 hours after light onset (HALO), and three during the dark phase, i.e. 15, 19 and 23 HALO. Whatever the circadian stage, the melatonin release decreased during the first 3-4 h and then remained fairly constant and roughly similar up to 8 h of perifusion. However, the kinetics of the release in the first 3 h differed in perifusions of pineal glands removed during the light (progressive decline during 3 h) as compared to perifusions of pineal glands removed during the dark (sharp decline during the first hour and then a progressive decline until reaching a constant level after 3 h). As the effects of steroid administration on melatonin secretion are a matter of controversy, we also studied the direct effects and their circadian stage dependence, if any, of corticosterone, deoxycorticosterone and dexamethasone on melatonin secretion by pineal glands removed 7 HALO (about the middle of the light phase) and 19 HALO (about the middle of the dark phase). High concentrations of corticosterone (0.8 x 10(-3) mol/l) and dexamethasone (0.4 x 10(-3) mol/l) resulted in a significant (p < 0.001) inhibitory effect on melatonin production (about a 50% and a 30% decrease, respectively) whatever the circadian stage, whereas lower concentrations (10(-4)-10(-5) mol/l) of both steroids did not affect melatonin production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8351961 TI - Pituitary-gonadal response to gonadotropin-releasing hormone stimulation is enhanced in men after strenuous physical exercise. AB - The effects of strenuous physical exercise were studied on the pituitary testicular response to gonadotropin-releasing hormone (GnRH) stimulation and on growth hormone (GH) and cortisol secretion. Eight healthy adult males were injected twice intravenously with 0.1 mg of GnRH at intervals of 21 days. At the time of the first injection (exercise trial) the subjects had been bicycling for 4 h on the road, and at the time of the second injection (rest trial) they had been resting in a sitting position for 4 h. Blood samples were taken before and after the 4-h period and 30, 60 and 120 min after the GnRH injection. Both testosterone and luteinizing hormone (LH) decreased during the exercise by 18% (p = 0.037) and 29% (p = 0.0028), respectively, but increased after the GnRH injection by 1.4- and 12.9-fold (p = 0.0001 for both). The areas under the testosterone and LH response curves after GnRH were significantly larger in the exercise trial than in the rest trial, threefold (p = 0.013) and 1.3-fold (p = 0.0007), respectively. Growth hormone and cortisol increased during the exercise trial. In the rest trial, the GnRH injection increased serum GH concentrations (p = 0.027). In conclusion, the diminished hypothalamic GnRH secretion seems to be the major cause of the post-exercise decrease in LH and testosterone, but altered sensitivity of the pituitary to GnRH also may be involved. Apparently, the build up of pituitary LH stores during exercise explains the enhanced LH and testosterone response to GnRH challenge after exercise in comparison to control GnRH challenge. PMID- 8351962 TI - Fine structural correlates of VIP-like immunoreactivity in the upper spinal dorsal horn after peripheral axotomy: possibilities of a neuro-glial translocation of a neuropeptide. AB - After transection of the peripheral nerve, VIP-like immunoreactivity (VIPLI) increases markedly in the ipsilateral upper dorsal horn of the spinal cord. Immunoreactivity has been studied by means of light- and electron microscopic immunocytochemistry. Under normal conditions, there is little VIPLI present in the superficial dorsal horn, confined to small dot-like elements corresponding to axonal and glial profiles. At the electron microscopic level, immunostaining was found mainly in preterminal and, partly, also in en passant terminal swellings or varicosities. The reaction was confined to the axoplasm and, to a lesser extent, to large dense core vesicles. VIPLI is also present in several astroglial processes. 13, 19, and 25 d after transection of the sciatic nerve, increased immunoreactivity was present in the medial 2/3 of the superficial dorsal horn. Electron microscopically, VIPLI was seen mainly in preterminal axons and in many astroglial processes surrounding axon terminals while VIPLI in the en passant axon terminals themselves decreases. 2 months after peripheral axotomy, the amount of axonally localized VIPLI decreases considerably and most of the immunocytochemically detectable VIPLI is found in expansions and processes of astroglial cells. Perikarya of glial cells rarely exhibit VIPLI. VIPLI also increased after crushing the related peripheral nerve; however, as soon as the nerve fibers regenerate, VIPLI decreases again to normal levels. It appears that blockade of the retrograde axoplasmic transport induces a switch in the neuropeptide synthesizing machinery of dorsal root ganglion cells which results in the expression of VIP instead of substance P, somatostatin and CGRP. It is proposed that VIP is released from axon terminals affected by transganglionic degenerative atrophy. Subsequently, astroglial cells equipped with receptors for VIP, might bind and internalize the released VIP. PMID- 8351963 TI - Intermediate filaments and ATPase activity in the vascular wall of vertebrates. AB - The vascular wall of aorta and vena cava was examined for adenosine triphosphatase (ATPase) activity and cytoskeletal intermediate filaments (IF) in different representatives of vertebrates. Enzyme activity was studied by the modified method of Padykula and Herman. A streptavididin-biotin immunohistochemical method was applied to reveal desmin (D) and vimentin (V) IF. Endothelial cells of all vessels were V-positive and D-negative and exhibit high ATPase activity. Vascular smooth muscle cells (SMC) in lower vertebrates (pisces and amphibia) were also V-positive and D-negative, but showed low ATPase activity. SMC were D-positive and V-negative and possessed high enzyme activity in aves and mammals, similar to that of the endothelium. In cow vascular wall D reactivity and high ATPase activity were mostly expressed in bundles of mosaically arranged thick SMC fibres of the outer aortic media as well as in the longitudinal fibres in the inferior vena cava. In higher vertebrates SMC of vasa vasorum were both V- and D-positive and showed high enzyme activity. The results demonstrate that D-immunoreactivity is mostly expressed in SMC of layers of high functional activity, which correlates with the intense ATPase reaction in these cells. PMID- 8351964 TI - Biphasic increase of calcitonin gene-related peptide-like immunoreactivity in rat hypoglossal motoneurons after nerve transection. AB - In the hypoglossal system the regulation of calcitonin gene-related peptide (CGRP) following peripheral nerve transection and prevention of reinnervation was studied using immunocytochemistry. In the adult rat axotomy resulted in a biphasic increase of CGRP-immunoreactivity (IR) with a first peak after 2 days and a second peak after 18 days. In addition to an increase in staining intensity the number of CGRP-IR motoneurons was also increased. The lesion-induced alterations of CGRP-expression in the hypoglossal nucleus correspond to those described in other motor system. A possible contribution of CGRP to degeneration/regeneration processes is discussed. PMID- 8351965 TI - Effect of fixation conditions on the granule morphology of rat antral gastrin cells: an ultrastructural and immunocytochemical study. AB - After fixation at pH = 7 or pH = 5 the gastrin (G) cells in the rat pyloric antrum were investigated by conventional and immunoelectron microscopy. After fixation at pH = 7 G cells contained numerous electron-lucent granules, a few electron-dense and intermediate granules while G cells had numerous electron dense and intermediate granules, and a few electron-lucent granules after fixation at pH = 5. Preembedding immunoelectron microscopy revealed that in G cells after fixation at pH = 7, gastrin immunoreactivity was mainly seen in the cytoplasm, cores of a few electron-dense and intermediate granules and in the periphery but not within the numerous electron-lucent granules; in G cells after fixation at pH = 5, gastrin immunoreactivity was mainly visible in the cores of numerous intermediate and electron-dense granules, in the periphery of a few electron-lucent granules, but weakly in the cytoplasm. Therefore, the variable electron density of G cells may reflect differences in the degree of the leakage of contents from the gastrum-containing granules into the cytoplasm during fixation. This phenomenon may be related to the acidity of the granule substances during intragranular maturation. PMID- 8351966 TI - Enzyme activities of six different dehydrogenases in Ehrlich ascites cells measured by flow cytometry. AB - Flow cytometric measurements of the activities of lactate dehydrogenase, glucose 6-phosphate dehydrogenase, isocitrate dehydrogenase, glycerol-3-phosphate dehydrogenase, succinate dehydrogenase and glutamate dehydrogenase in single Ehrlich ascites tumour cells are described using a tetrazolium salt/fluorescent formazan reaction. Applying cyano-ditolyl-tetrazolium chloride (CTC) as redox dye indicating enzyme reaction, and DAPI as a fluorochrome for nuclear DNA staining, the bivariate flow cytometric assay of enzyme activity and cell cycle analysis was established. Furthermore, adopting the calibration procedure reported formerly, consisting of biochemical determination and flow cytometry of the same sample performed parallelly, the enzyme activities were expressed in biochemical units. The dehydrogenase activities found in Ehrlich ascites cells were 97.5 fmol H2 per average positive cell during 5 min for lactate dehydrogenase, 69.0, 10.6, 25.3, 29.7, and 19.0 fmol H2 per average positive cell during 20 min for glucose 6-phosphate dehydrogenase, isocitrate dehydrogenase, glycerol-3-phosphate dehydrogenase, succinate dehydrogenase and glutamate dehydrogenase, respectively. This quantitative procedure can offer an alternative analytic tool for enzyme cytology. PMID- 8351967 TI - Proteases of polymorphonuclear neutrophils: influence of different salts and buffers on pericellular lysis. AB - Polymorphonuclear neutrophils (PMN) contain neutral proteases which are cytochemically detectable on blood smears. The activity of these proteases can be visualized by pericellular lysis, i.e. through a disk like degradation of plasma and erythrocytes around centrally located neutrophils. This degradation is inhibited by protease inhibitors in a concentration-dependent manner. Striking differences in halo formation were found depending on the type of buffer and salt used and change of temperature. A halo formation was obtained in Tris-HCl buffer, pH 7.5 without salt, at room temperature (22 degrees C), and with short incubation periods (30 min). Borate buffer, pH 8.5, showed a comparable halo formation only at 37 degrees C, after addition of salts, and after longer incubation times (180 min). When different alkali chlorides were used, halo size increased with molecular mass. Optimum halo size was achieved at a concentration of 250 mM. Addition of MgCl2 and CaCl2 (250 mM) resulted in a small halo formation at 22 degrees C, but inhibited halo formation at 37 degrees C. The present study shows that the pericellular lysis caused around neutrophils by the release of proteases is affected by a complex interaction of salts, temperature, buffers and thermodynamic aspects, all of which should be evaluated carefully in these kinds of experiments. PMID- 8351968 TI - Effects of the fluorescence dye DAPI on microtubule structure in vitro: formation of novel types of tubulin assembly products. AB - It has been found that the DNA fluorescence dye 4',6-diamidino-2-phenylindole (DAPI) is able to stain also microtubules. However, electron microscopy revealed that DAPI changed microtubule structure and induced the formation of a broad spectrum of polymorphic tubulin assembly products. Upon addition of DAPI to microtubules assembled from 10 to 15 mumol tubulin (molar DAPI/tubulin ratios of 10 to 40) in the presence of microtubule-associated proteins, most of the microtubules were decorated with additional protofilaments usually running parallel to the protofilaments of the microtubule wall (microtubule-protofilament complexes). When DAPI was already present during assembly, curved C- and S-shaped protofilament ribbons and microtubule-ribbon complexes with 6-shaped profiles were the most prominent products, beside microtubules. Additionally, protofilament bundles, some flat sheets, and hoops occurred. Electrophoresis revealed that DAPI lowered the amount of associated proteins, especially of tau proteins, bound to the assembly products. Nevertheless, DAPI stimulated the assembly, enabled pure tubulin to assemble even at concentrations as low as 10 mumol, and stabilized the assembly products against cold. The microtubule protofilament complexes, observed for the first time, are interpreted as the result of DAPI-induced protofilament linking as well as of activation of an additional tubulin-tubulin binding site which is possibly identical to that involved in the formation of microtubule doublets. PMID- 8351969 TI - Distribution of carbonic anhydrase isozyme III (CA-III)-positive cells in duct segments of the bovine submandibular gland. AB - The distribution of carbonic anhydrase III isozyme (CA-III)-positive cells in bovine submandibular glands was studied by immunohistochemistry. CA-III showed strong immunoreactivity in basal cells and some lining cells of the intercalated ducts as well as in striated and interlobular ducts cells. No significant immunoreactivity could be found in other portions of the glands. Electron microscopically, the immunoreactive basal cells contained scattered tonofibrils in their cytoplasm. The distribution of CA-III suggests that the CA-III-positive basal cells may play a special physiological role, and that they do not only represent undifferentiated lining cells. PMID- 8351970 TI - Type IV collagen localization in hamster tracheal epithelial cell cultures. AB - Hamster tracheal epithelial (HTE) cell cultures when grown on collagen coated Millicell-HA filters for 28 d in vitro have an incomplete basal lamina-like structure at the basal plasmalemma/collagen interface. EM evaluation of 42 d HTE cell cultures also revealed the presence of hemidesmosome-like structures on the basal plasmalemma. In order to better characterize this discontinuous basal lamina-like material, HTE cultures at 7, 14, 21, and 28 d were evaluated for the presence of type IV collagen, a basal lamina component. Immunocytochemical treatment of HTE cultures at these time points resulted in the presence of reaction product at the base of the cell layer. When immunocytochemical procedures for the localization of type IV collagen were carried out with normal mouse trachea, the results were also positive. Immunoblotting evaluation of HTE cell supernatants and conditioned media also indicated the presence of type IV collagen. Taken altogether, the presence of what appears to be basal lamina, hemidesmosome-like structures and immunocytochemical and immunoblot data showing the presence of type IV collagen in HTE cultures suggest that HTE cells may be producing basal lamina components but cannot organize them into a complete basal lamina. PMID- 8351971 TI - Immunolocalization of meprobamate-like molecules in rat cerebellar cortex. AB - The localization of meprobamate-like (MPB-like) molecules in the cerebellar cortex of the rat was investigated with the peroxidase-antiperoxidase (PAP) immunocytochemical method using an antiserum raised in rabbits. The positive immunoreaction for MPB in several nervous structures and in the wall of blood capillaries suggest the presence of endogenous MPB-like molecules. PMID- 8351972 TI - Immunohistochemical phenotypes of histioeosinophilic granulomas of thymus and reactive eosinophilic pleuritis. AB - Immunohistochemical phenotyping of 7 cases of histioeosinophilic granulomas of thymus and 4 cases of reactive eosinophilic pleuritis was performed. All 11 cases of these 2 entities reacted identically. This supports the view that these 2 lesions are similar in nature. Both lesions are reactions to the presence of insufflated gas and its resorption. PMID- 8351973 TI - Chick embryo metanephros: the glycosylation pattern as revealed with lectin conjugates. AB - Fragments of metanephros were taken from chick embryos and studied from the 7th to the 21st d of incubation. A battery of 7 different horseradish peroxidase labelled lectins (PNA, ConA, DBA, SBA, LTA, WGA and UEA I) was used to analyse the distribution and changes of carbohydrate moieties in glycoconjugates along the metanephric nephron from the S-shaped body stage onwards. DBA and SBA reacted for a short time at some sites during the considered period of incubation. Provided WGA and ConA reacted with most of the nephric components, the almost ubiquitous presence of N-acetyl-D-glucosamine and alpha-D-mannose was demonstrated. SBA and LTA were found to be good markers of the proximal tubule. On the 12th d of incubation, sialic acid was found in the podocytes, capillary walls, and the connecting and collecting ducts. On the same day, other oligosaccharides were present at the nephric tubular components. The simultaneous presence of sialic acid and other sugar residues may be significant for the identification of the exact stage of incubation at which metanephric activity starts. The possible role of some sugar residues for the regulation of metanephric activity is discussed. PMID- 8351974 TI - Morphometric analysis of the hypoactivity of FSH-immunoreactive cells in estrogen primed male rats. AB - In order to evaluate the repercussions of estradiol treatment on the morphology and activity of FSH-producing cells, an immunocytochemical and morphometric study was carried out in male rats treated chronically with estradiol, relating those findings to serum FSH levels at the time of sacrifice. Chronic administration of estradiol led to a decrease (p < 0.01) in serum hormone levels that was accompanied by a marked decrease in cellular size (p < 0.01) due to a decrease in nuclear and cytoplasmic area. Our findings suggest for the adult male rat an inhibitory effect on the synthesis and release of FSH following testicular atrophy induced by treatment with estradiol. PMID- 8351975 TI - Immunological cross-reactivities between proteins secreted by the subcommissural organ, and plant lectins. AB - The glial subcommissural organ (SCO) discharges a glycoprotein-rich secretory product into the third ventricle to form Reissner's fibre (RF). The SCO proteins bear N-linked oligosaccharides, such as mediate many cell-cell and cell-matrix interactions. In such interactions the corresponding partner molecule recognising the sugar chain is often a sugar-specific protein (lectin). We present here evidence that the constituents of the SCO secretory product include proteins immunologically cross-reactive with certain plant lectins. Polyclonal antisera directed against Phaseolus vulgaris agglutinin-L (PHA-L) labelled the apically released RF-material of the rat SCO. Indirect ELISA studies shows in addition that anti-RF antisera bound to certain plant lectins (PHA-L, Con A). Dot spot assays demonstrated binding of anti-PHA-L to RF proteins. In Western blots of RF proteins anti-PHA-L, anti-RCA and anti-Con A bound to distinctive subsets of the RF protein fractions. PMID- 8351976 TI - Enzyme cytochemical expression of aortic smooth muscle cell modulation in primary and secondary cultures. AB - "Contractile" arterial smooth muscle cells (SMC) return to a less differentiated "synthetic" state during adaptative and proliferative processes in vitro and in cell cultures. At present, the enzyme expression of the modulation of cultured SMC is partially unknown. In order to define metabolic events associated with cell modulation in vitro, we studied 16 enzyme activities in primary and secondary (P1-P3-P10) SMC cultures in comparison to in situ SMC in fetal and adult rat aorta. The "contractile" SMC in aorta of 2 months old rat showed very high nucleotide hydrolase activities (5'-nucleotidase, Mg-ATPase, Ca-ATPase), and naphthylesterase activities and weak lysosomal acid phosphatase activity; the glycolysis-linked dehydrogenases were expressed with higher activities than Krebs cycle-linked enzymes. In primary cultures, the SMC near the explant expressed a "contractile-like" enzyme behaviour, in opposite to cells in the peripheral part of growing area enzymatically similar to sub-cultured SMC. Proliferating SMC in secondary cultures were characterized by increased lysosomal activities and by the decrease or disappearance of Ca-ATPase, Mg-ATPase, 5'-nucleotidase, and butyrylcholinesterase activities like fetal SMC in vivo. These enzyme changes in subcultures might be related to a deficiency of nucleotide ester hydrolysis, abnormal adenosine and AMP levels, lowered lipolytic capability and increased lysosomal reactivity. In conclusion, subcultured "synthetic" SMC expressed enzyme cytochemical patterns different from those of "contractile" SMC and similar to those of fetal immature SMC. Their enzyme behaviour is unfavourable to contractile function and favourable to cell proliferation and lipid accumulation, two characteristic features of SMC in atherosclerotic plaques. PMID- 8351978 TI - Variations of collateral branching in the motor nerve fibers in the skeletal muscle of adult rats. AB - Collateral branching (CB) applies to a collateral branch resulting in the innervation of two or more muscle fibers by one motor axon. Using a silver impregnation with or without cholinesterase (ChE) staining, the morphological pattern of innervation was investigated in the motor endplates of the adult rat soleus. Two types of variations of CB, type A and B, were noted. In type A (elaboration of CB), marked ramification of a single motor axon results in double, discrete endings (main and smaller accessory endings) on one muscle fiber and collateral formation on the other. The accessory endings were apposed by some small, clearly-defined separated units of the postsynaptic ChE site. In type B (double endings per endplate), small endings lying close to the main ending were either due to ramification of the motor axon innervating the neighboring muscle fiber (type B 1) or due to direct contact of non-branched, non-original motor axons (type B 2). The incidence of CB and its variations was small and the number of subterminal axons innervating more than one muscle fiber (functional terminal innervation ratio) was far below the level of partial denervation. In response to the local events of muscle, either type A or type B branching could serve as a useful tool to remodel the motor endplate for, e.g., its renewal, replacement and/or enlargement. PMID- 8351977 TI - Analysis of lectin binding sites in the gut of hooded Lister rats with special emphasis on recently detected lectins. AB - Seven recently isolated lectins were tested for their ability to bind to tissue sections of rat gut. Binding sites for N-Acetylgalactosamine specific lectins were found in mucins, in the brush border membrane and in goblet cells. Non reducing terminal mannose residues were absent from cell surface membranes but were detected in the supranuclear region of goblet cells and enterocytes. The results of lectin binding obtained in this study were generally similar to lectin gut interactions observed in vivo. PMID- 8351979 TI - The use of lectins identified with specific antibodies in lectin histochemistry of NZB/W F1 mouse kidney. AB - The affinity of Helix pomatia, peanut, Pisum sativum, soy bean, and wheat germ agglutinins to various nephron parts of NZB/W F1 mice was different and is assumed to be age dependent. The affinity of Pisum sativum agglutinin to basal membranes of small renal vessels increased with the age of NZB/W F1 mice. The wheat germ agglutinin bound to structures with alkaline phosphatase activity. PMID- 8351980 TI - Neuronal expression of the RAF protooncogene in the spinal cord of adult guinea pigs. AB - The cellular raf oncogenes encode cytoplasmic serine/threonine specific protein kinases. Since there are some indications that they are involved in neuronal plasticity, we investigated the localization of raf protein kinases immunohistochemically. The spinal cord of adult guinea pigs was fixed by means of transcardial perfusion, transverse sections were cut from each segment and stained with monoclonal and polyclonal antibodies, raised against synthetic raf peptide and recombinant raf protein, respectively. The motor neurons of the ventral horn and the large- and medium sized neurons of laminae I, IV, V, VI, VII and VII were stained in every segment of the spinal cord. The widespread occurrence of raf kinases in the spinal cord and the literature data indicating their participation in growth factor mediated processes, raise the possibility that the raf protooncogenes play a fundamental role in the regulation of transmembrane signalling of these neurons. PMID- 8351981 TI - Definition and classification of childhood injuries. AB - Injuries have emerged as the leading cause of child and adolescent morbidity and mortality in developed countries. Efforts to control injuries require injury surveillance and research, creating the need for standard variable definitions and categorizations. Advantages of such standardization include increased comparability of data sets, avoidance of spurious conclusions based on idiosyncratic definitions and categories and the potential to combine data sets (e.g. on injuries and population counts) to yield new information. Pertinent standards will differ depending on the purposes for which the data are collected. More limited (core) data are appropriate to surveillance and more extensive data to research. Existing standards that are likely to be most useful to pediatric injury investigators are the International Classification of Diseases External Cause (E) codes (which provide mechanism-of-injury diagnoses and are the international gold standard for injury data reporting) and the Standard Definitions for Childhood Injury Research recently released by the United States National Institute for Child Health and Human Development, which include both core and complete variable listings. Some key core definitions from the latter report are presented. PMID- 8351982 TI - Injury surveillance in Australia. AB - The development of injury surveillance systems in Australia is described from a public health perspective at the national level. Injury surveillance systems have undergone significant changes in recent years and further developments are planned. Three phases or generations are distinguished, each with distinctive features, advantages, and disadvantages. The first generation system was based on by-product data from routine mortality and morbidity statistics. The second generation system was specifically designed for injury surveillance, mainly using data collected for this purpose in hospital accident and emergency departments. A third generation of public health surveillance systems for injury control is now being developed for Australia. In developing a third generation system, a middle course is being charted. The number of data items and the complexity of classification for routine surveillance are mid-way between those of the first and second generation systems. PMID- 8351983 TI - Childhood injuries in Japan. AB - Approximately 2000 children aged between 0 and 14 years die annually of accidents and their sequelae in Japan. Moreover, accidents and their sequelae are the leading cause of death in the 1-4 year, 5-9 year and 10-14 year age groups. Accidental drowning and traffic accidents account for 2/3 of all such deaths. Measures for preventing injury in these age groups are clearly necessary, since the mortality rate due to accidents and their sequelae in children 0 to 4 years old is higher in Japan than in European countries. It is considered that the lives of 824 infants aged between 0 and 4 years might be saved annually in Japan if the mortality rate could be reduced to a level comparable to that in Sweden by accident prevention and control. Therefore, a systematic approach for prevention of childhood injury is a high priority in Japan. PMID- 8351985 TI - Accidental poisoning of children in Japan: a report from the Japan Poison Information Center. AB - The Japan Poison Information Center (JPIC) was founded only 6 years ago as a result of co-operation between the Ministry of Health and Welfare, the Japanese Association for Acute Medicine, the Japan Pediatric Society and other related medical organizations. The JPIC is the only poison information center admitted by the Ministry of Health and Welfare to provide toxicological information to medical personnel and the general public, and has two offices on duty in alternating 24 h shifts. Every year, JPIC receives about 30,000 inquiries. About 82% of these inquiries are from the general public and 84% of the patients are children 5 years and younger. We contrasted the data in the fiscal year 1991 with the data of the American Association of Poison Control Centers (AAPCC). Child poison exposure in Japan is characterized by a high exposure rate of children under 1 year of age to (mostly) household products. The JPIC also analyzed the cause of tobacco ingestion. It is considered that the Japanese lifestyle causes differences from those reported by AAPCC. We report the accidental poisoning of children in Japan. PMID- 8351984 TI - Childhood drownings and near-drownings in Japan. AB - In Japan, the leading cause of death for children over 1 year old is injury, and for children aged 0-14, drowning is the second leading cause of death. The purpose of the present study was to describe the epidemiological factors of drownings and near-drowning among Japanese children and to ascertain whether there are characteristic patterns for different age groups. Epidemiologic data was obtained by questionnaire. A total of 604 cases of submersion injuries were reported from 49 hospitals located in 22 Japanese prefectures. In the present paper, victims of drowning (n = 134) and near-drowning with permanent severe brain damage (n = 51) and those of near-drowning with intact survival or mild impairment (n = 419) were investigated. Preschool-aged children, especially toddlers, are at the greatest risk of drowning and near-drowning, and for children over 2 years of age, boys have three times greater risk than girls. The bathtub is the most common place of submersion injuries in Japan, especially for children under 4 years of age. The important risk factors for the victims who died or were severely impaired were associated with duration of submersion and necessity of emergency cardiopulmonary resuscitation on arrival at hospital. PMID- 8351986 TI - Injuries of school-aged children in Japan: causes and costs. AB - Injuries of school-aged children were presented from several data sources. About 80,000 schools, from nurseries to upper secondary schools, operate in Japan and are attended by 24.3 million students. About 97% of these young people are insured by the insurance system of the School Safety Division of the National Stadium and School Health Center of Japan. Annual injuries and illnesses total 1.08 million, 1039 cases being impedimentary and 191 causing death. The average incidence of injury and illness is 4.6%, a rate that has been increasing every year since 1960. The activity at the time of injury, the impairment incurred, and the part of the body injured differ with the type of school and depend mainly on the developmental stage of the child. Minor injuries occur at the rate of about 47 cases in elementary schools and 14 in lower secondary schools versus one benefit-applied injury at a school safety center. The cost of injuries under the control of schools totaled US$124 million per year in 1990. The average amount of benefits per injured student per month was US$63. PMID- 8351987 TI - Child traffic accident injuries in Japan. AB - This study analyzes the characteristics of traffic accidents involving children. It discusses why children with certain attributes and in specific situations are exposed to a higher traffic accident risk, in light of their ability to deal with traffic and their body characteristics. Finally, based on these results, it offers some conclusions and recommendations on ways of improving child safety in road traffic. PMID- 8351989 TI - Role of a children's hospital safety centre in injury control. AB - Over the past 13 years, child safety centres have been established at several Australian Children's hospitals. In a short time, they have developed an important role in community injury control programmes. These centres provide an efficient conduit for transferring up-to-date injury surveillance and prevention information to families, industry, health and education professionals, and government. The activities of the Child Safety Centre at the Royal Children's Hospital in Melbourne are described, together with ways in which a degree of self funding can be achieved. PMID- 8351988 TI - Preventing accidents in childhood: a European perspective. AB - Accidental injury is a principal public health issue with important individual, societal and economic consequences. Crude figures show that 2.7 million deaths from injury and poisoning are reported worldwide. In developing and industrialized countries 10-30% of all hospital admissions are due to accidental injuries. In particular, children and adolescents are at risk. In all industrialized countries accidental injuries are the major cause of death and morbidity among children above the age of one. In the domestic safety area much effort has to be invested in improving the safety of the environment and products. In the European region, collaboration among authorities in the framework of the European Community (EC) has been shown to be productive in the area of safety. Although trade interest is predominant in the EC objectives, the need to harmonize national regulations and standards towards common European standards has appeared to be an important vehicle for establishing standards at an optimum level of safety. It has also fostered some collaboration in data collection and analysis and in implementing prevention measures. An even stronger international collaboration is needed for ensuring that appropriate priorities are being set and prevention measures are effectively being implemented. PMID- 8351990 TI - Influence of long-term carbamazepine treatment on thyroid function. AB - We have studied the effects of carbamazepine on thyroid function in sixteen recently diagnosed epileptic children and thirteen epileptic children receiving long-term carbamazepine therapy and compared these findings with the thyroid function of thirteen healthy control subjects. Thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4) serum levels were determined in both recently diagnosed but as yet untreated epileptic children and normal controls. These hormone levels were determined again after 2 months of treatment and 12 months of treatment in epileptic children. No statistically significant difference was found in the endocrine parameters of untreated epileptic children and the normal control group. After both 2 months and 12 months of carbamazepine therapy, serum levels of T4, FT4 and FT3 were found to be low, but the serum T3 concentration was unaffected. Baseline TSH levels were not changed during carbamazepine therapy either. Serum TSH levels increased rapidly after thyrotropin-releasing hormone stimulation in both the before and 12 months after carbamazepine treatment groups, but the response was higher in the 12 months treatment group. The findings of the present study suggest that accelerated hormone metabolism is responsible for hormonal changes found in patients treated with carbamazepine. Carbamazepine also had effects on the function of the hypothalamo-pituitary axis. PMID- 8351992 TI - Increased level/dose ratio of amphotericin-B in premature infants with renal failure. AB - We introduced continuous intravenous infusion of amphotericin-B (AMPH-B) to extremely low birthweight (ELBW) infants (< 1000 g) with or without renal failure as a single agent for treating definite or probable systemic candidiasis. The species of Candida isolated from blood or tracheal aspirate or urine were C. albicans in seven infants, C glabrata in two, C. tropicalis in one and C. parapsilosis in one. The minimal inhibitory concentrations (MIC) of AMPH-B required against these isolates were less than 0.2 micrograms/mL except for that against one strain of C. albicans (0.78 microgram/mL). Serum AMPH-B levels were 0.31-0.78 (0.51 +/- 0.14) micrograms/mL when doses of 0.2-0.55 (0.32 +/- 0.11) mg/kg per day were being administered. The serum level was higher than the MIC of each isolate in all but one infant who died of disseminated intravascular coagulation and Candida pneumonia. Another infant died of congenital heart disease. The other nine infants survived. The serum level showed no correlation with the daily dose. The ratio of the serum level to the daily dose (L/D ratio) showed a significant correlation to serum creatinine (r = 0.787) and the linear regression curve followed the equation: L/D ratio = 0.223 x serum creatinine + 1.11 (P < 0.01). Few adverse effects due to AMPH-B were noted. Our data may give a simple reference to serum AMPH-B levels during continuous intravenous infusion from the dose and the serum creatinine level. PMID- 8351991 TI - Respiratory syncytial virus infection in lower respiratory tract and asthma attack in hospitalized children in North Hokkaido, Japan. AB - Respiratory syncytial virus (RSV) infection is severe and life-threatening in some infants. To investigate the epidemiology of RSV infection in hospitalized children in North Hokkaido, Japan, we tried to detect RSV antigen in nasopharyngeal aspirates (NPA) from those children with lower respiratory tract infection (LRTI) and asthma attack. From April 1991 to March 1992, 317 patients were hospitalized in our pediatric ward for the treatment of LRTI and asthma attack. The presence of RSV antigen in NPA taken from 283 patients (89.3%) were examined by enzyme immunoassay. RSV antigen was detected in 88 patients (31.1%). RSV LRTI were noted throughout the year, and the epidemic peak was observed in November and December. There was no significant correlation between the RSV antigen positive rate and mean temperature. RSV played an important role in LTRI in children in North Hokkaido, Japan. RSV LRTI in North Hokkaido was not rare in summer, indicating that RSV was transmitted commonly among children throughout the year. PMID- 8351993 TI - Echocardiographic findings in mild and severe forms of sickle cell anemia. AB - M-mode echocardiographic findings were compared between sickle cell anemic and healthy children. Patients were composed of two groups; Group 1: mild group with no crises, no blood transfusions at the ages of 5.0 to 13.0, total of 12 children; Group 2: severe group, with frequent crises with requirement of blood transfusions at the ages of 3.0 to 13.0 years, total of 18 children. Control group was composed of 12 healthy children aged 5.0 to 13.0. When M-mode echocardiographic findings were compared, important findings were as follows: Mean left atrium dimension was increased both in the mild and severe groups (P < 0.001) compared with controls. This finding also supports the increase in the left ventricle end-diastolic dimension in both the severe and mild groups as compared with controls (P < 0.001). The increase in end-diastolic left ventricle dimension could be due to anemia present in the patients, but there was no difference between the two patient groups. Posterior left ventricle thickness and left ventricle mass was increased in both the mild and severe groups compared with controls (P < 0.001, P < 0.05), respectively. Left ventricular fractional shortening was more or less the same with controls. In spite of left ventricular volume load and dilatation, left ventricular contraction was good and systolic function was normal, and there was no correlation between the ECHO findings and hematological indices. PMID- 8351994 TI - A new and rare form of Williams' syndrome. AB - A 7 year old girl and her mother have typical phenotypic features of the Williams' (elfin facies) syndrome, and both have only mild mitral regurgitation with mitral valve prolapse (MVP). Mitral valve prolapse has been reported in only three cases but pure mitral insufficiency has not been reported alone. In this paper two cases of a new rare form of Williams' syndrome with MVP are presented and this rare disorder is discussed. PMID- 8351995 TI - Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings. AB - A 13 year old girl with carpopedal spasm is presented. Investigation values showed hypomagnesemia and hypokalemia. Her younger brother and sister demonstrated the same biochemical abnormalities without any symptoms. Their urinary excretion of magnesium and potassium were inappropriately high compared with their serum levels. Treatment with oral magnesium sulfate failed to correct the abnormalities, but serum levels of magnesium and potassium were just below the lower limits. This familial disease may represent congenital renal wasting of magnesium and potassium. PMID- 8351997 TI - A case of urethral prolapse in a young girl. AB - Urethral prolapse is rarely reported in the pediatric literature. We report a 4 year old female with urethral prolapse and discuss the etiology and the treatments in children documented in the literature. PMID- 8351996 TI - A mild case of nesidioblastosis with diagnostic and therapeutic difficulty. AB - A female infant with nesidioblastosis who showed mild clinical symptoms is reported. In this patient, insulin levels and insulin to glucose ratios (IRI/G) were often normal. Regular milk feedings supplemented with continuous glucose infusion (0.7-2 mg/kg per min) or oral glucose feedings (4.5 mg/kg per min) prevented hypoglycemia. As leucine-sensitivity was diagnosed at 2 months of age, she was started on diazoxide. This was, however, ineffective, and adverse effects appeared. Subtotal pancreatectomy (95%) was therefore attempted at 5 months of age, and persistent normoglycemia as well as normal growth and development followed up to 3 years after the operation. The pancreas showed characteristic signs of nesidioblastosis. The above clinical observation suggests that a patient with nesidioblastosis whose blood glucose level is easily controllable may develop an unexpected episode of hypoglycemia in the presence of a leucine sensitivity. In such a patient, diazoxide or, when it is of no avail, surgical intervention should promptly be instituted to prevent possible neurologic sequelae induced by hypoglycemia. PMID- 8351998 TI - Relation of age to effects of phentolamine and phenylephrine on heart. AB - In the present study, the responses of neonatal and adult dog hearts to phenylephrine (PE) and phentolamine (PA) were investigated in order to determine the influence of age factors. PA resulted in the slowing of the heart rate, the prolongation of corrected sinus node recovery time, atrial refractory period (ARP), ventricular effective refractory period (VERP), and ventricular functional refractory period (VFRP), and a significant inhibition of conducting tissues in neonatal dogs. In contrast, no such effects were seen in adult dogs. PE had a positive chronotropic effect in neonatal dogs but no such effect in adult dogs. In conclusion, alpha-adrenoceptors played an important excitatory role in the neonatal dog heart. PMID- 8351999 TI - Endocardium modulates myocardial contractile performance in isolated guinea pig papillary muscles. AB - Selective removal of endocardium by 1-s immersion of the muscle into 0.5% Triton X-100 resulted in a significant reduction of PT (peak isometric twitch tension) at 1.25 mmol.L-1 [Ca2+]o over the stimulation frequency from 0.2 to 2.0 Hz (3.2 +/- 0.2 vs 4.4 +/- 0.4 mN/mm2 at 1 Hz, P < 0.01), while +dT/dtmax was unaltered. Tension-[Ca2+]o relation was shifted in accordance to [Ca2+]o, but with no significant change on PT at high [Ca2+]o compared with endocardium-intact muscles. TPT (time to peak isometric tension) and RT1/2 (half isometric relaxation time) were typically shortened at all [Ca2+]o or various stimulation frequencies (TPT: 203 +/- 18 vs 265 +/- 37 ms; RT1/2: 77 +/- 10 vs 108 +/- 26 ms, at 1.25 mmol.L-1 and 1 Hz, P < 0.01). Stimulation duration-threshold curve was slightly shifted to the left, yet no change in ERP (effective refractory period) was found. The data demonstrated that endocardium was an important modulator of myocardial contractile performance. PMID- 8352000 TI - Effects of rhynchophylline on motor activity of mice and serotonin and dopamine in rat brain. AB - Rhynchophylline (Rhy) reduced the spontaneous motor activity and enhanced the sedative and hypnotic effects of sodium pentobarbital in mice. The effects of Rhy on serotonin (5-HT) and dopamine (DA) concentrations in rat brain, and the release of 5-HT and DA from the regional brain slices were studied by a fluorescence detector. Rhy increased the 5-HT content in the hypothalamus and cortex, but reduced the DA concentrations in the cortex, amygdala, and spinal cord. Rhy promoted the release of endogenous DA from 4 brain regions. The release of 5-HT was increased in 2 brain regions and decreased in hypothalamus slice. However, Rhy inhibited the release of both 5-HT and DA evoked by high potassium. PMID- 8352001 TI - Effects of argipressin injected into medial amygdaloid body on blood pressure and heart rate in rats. AB - Graded injections of argipressin (Arg, 150, 300, and 600 ng/1.5 microliters CSF, 2 min) into the medial amygdaloid body in anesthetized rats produced a dose related increase in the mean arterial pressure and heart rate (Maximal delta MAP = 2.9 +/- 1.5 kPa, Maximal delta HR = 67 +/- 38 bpm), which lasting > 40 min at 600 ng dosage. Naloxone (15 micrograms/15 microliters CSF) injected into the lateral ventricle blocked the cardiovascular responses to Arg. These results suggest that Arg exerts a central action on the cardiovascular system via the opioid in the lateral ventricle. PMID- 8352003 TI - Selective vasodilatory effect of dipfluzine on vertebral artery in anesthetized dogs. AB - Dipfluzine (Dip) is a novel calcium antagonist first developed by Department of Chemistry, Beijing University. The effects of Dip on hemodynamics and vascular resistance in vertebral (VVR), coronary (CVR), and femoral (FVR) arteries were compared with those of cinnarizine (Cin) in anesthetized dogs. Dip iv decreased dose-dependently VVR at 0.1, 0.3, 1, and 3 mg.kg-1, CVR at 3 mg.kg-1, and FVR at 1 and 3 mg.kg-1. The fall of VVR by Dip iv was more remarkable than that by Cin at the matching doses. The systolic, diastolic, and mean blood pressure and total peripheral resistance were temporarily reduced equally by both of them at 1 mg.kg 1 iv, while Dip and Cin produced no obvious changes in heart rate, cardiac index, stroke index, LVP, and dP/dtmax at all doses. These results suggested that Dip possessed a high selectivity at different sites of the vasculature and was a more potent selective cerebral vasodilator than Cin. PMID- 8352002 TI - Effects of 3,6-dimethylamino-dibenzopyriodonium edetate on action potentials in guinea pig papillary muscles. AB - The effects of 3,6-dimethylamino-dibenzopyriodonium edetate (IHC-72) on action potentials (AP) and slow response action potentials of guinea pig papillary muscles were studied with intracellular microelectrodes. IHC-72 12.7, 25.4, and 50.8 mumol.L-1 decreased the maximal upstroke velocity (Vmax), amplitude of action potential (APA), over shot (OS), and resting potential (RP) while prolonged the action potential duration at 30%, 50%, 90%, and 100% repolarization (APD30, APD50, APD90, and APD100). IHC-72 25.4 and 50.8 mumol.L-1 decreased the APA, Vmax, and prolonged APD50 and APD90 under high K+ superfusion. IHC-72 25.4 and 50.8 mumol.L-1 depressed the automaticity, APA, and maximal diastolic potential (MDP) of the slow response action potentials induced by BaCl2. The results indicated that IHC-72 might nonspecifically inhibit the transmembrane movement of Ca2+, Na+, and K+. PMID- 8352004 TI - Effects of tetrahydroberberine on ischemic and reperfused myocardium in rats. AB - The effects of tetrahydroberberine (THB) on ischemic and reperfused myocardium were studied in comparison with verapamil (Ver). In anesthetized rats, THB and its analogues, l-THP and l-SPD, reduced the infarct size after 4 h of left anterior descending coronary artery (LAD) ligation. In Langendorff hearts, in common with Ver, THB 1 and 10 mumol.L-1 markedly decreased the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) in the reperfusion period. The malondialdehyde content and xanthine oxidase activity were also decreased in global ischemic-reperfused hearts pretreated with THB (P < 0.01, or P < 0.05). It suggested that THB could protect the myocardium from ischemic and reperfusion injury. PMID- 8352005 TI - Methylflavonolamine protects aorta from atherosclerosis in cholesterol-fed rabbits. AB - The effect of methylflavonolamine [4'-methyl-7-(2-hydroxy-3-isopropylamino propoxy)-flavone hydrochloride, MFA], synthesized recently by the Shanghai Institute of Pharmaceutical Industry, on the development of atherosclerosis was studied in male New Zealand white rabbits fed cholesterol for 10 wk. MFA, 7 mg.kg 1 daily ip, did not significantly alter the serum total cholesterol, HDL, and triglyceride levels, but significantly lowered the aortic cholesterol and calcium contents. Atheromatous lesions covered 53.3 +/- 11.8% of the intimal surface of the aorta in the saline group and 11.3 +/- 2.3% in the MFA group (P < 0.01). We conclude that MFA suppresses cholesterol-induced atherosclerosis. PMID- 8352006 TI - Optimal conditions of chemotherapeutic sensitivity in K562 cell line using tetrazolium dye assay. AB - Ten antineoplastic agents were used on K562 cell lines with the tetrazolium salts (MTT) assay to investigate optimal conditions of the chemotherapeutic sensitivity. The doubling time of K562 cell was 20.4 h in 96-well microtitre plates. The optical density in MTT assay of the no-drug controls was 0.77 (n = 45). A 70% reduction (IC70) in absorbance compared with control values using an ELISA reader at 570 nm was referred to as drug sensitive and < 70% (IC70) was referred to as resistant. The inhibitory effect of the theoretical maximal plasma drug concentration (Cmax) in plasma was compared with that of 10% Cmax drug concentration. At 10% Cmax after a 2-d drug exposure to daunorubicin and homoharringtonine, or after 5 d to epirubicin, 5-fluorouracil, cytarabine hydrochloride, and doxorubicin, significant cytotoxicities were shown. There were little time-dependent effects after 2-5 d drug exposure for 4 out of the 10 tested drugs, and mild or marked time- and dose-dependent effect for others. PMID- 8352007 TI - Inhibition of spermine on calcium influx during capacitation of guinea pig spermatozoa in vitro. AB - To investigate the mechanism of action of spermine, we measured the intracellular calcium ([Ca]i) of guinea pig spermatozoa using a probe of fluorescence, Quin 2. Results showed that spermine (0.25-2.0 mmol.L-1) suppressed the membrane permeability to Ca2+ during capacitation, which was similar to that of verapamil (a Ca2+ channel blocker). Furthermore, the rapid increase of [Ca]i induced by calcimycin (A-23187) was inhibited by spermine and verapamil, whereas trifluoperazine (an inhibitor of calmodulin) had no effect on it. The inhibition of the acrosome reaction caused by verapamil (5-100 mumol.L-1) or trifluoperazine (1-60 mumol.L-1) was reversed by calcimycin and cAMP, respectively. In addition, there was no effect on the initiation of the acrosome reaction when verapamil was added to capacitated spermatozoa. This result was in agreement with that of spermine. When addition of spermine (0.5 mmol.L-1) was combined with trifluoperazine (5 mumol.L-1), the acrosome reaction decline almost to zero, indicating that spermine might inhibit Ca2+ sensitive channel during sperm capacitation. PMID- 8352008 TI - Hypoxanthine phosphoribosyl transferase assay of lead mutagenicity on keratinocytes. AB - An improved hypoxanthine phosphoribosyl transferase (HPRT) assay system was used to investigate the genotoxicity in human and rat keratinocytes exposed to Pb2+ 0.1-100 mumol.ml-1 in vitro. Autoradiography was applied to determine the number of labeled cells/cm2 of culture with [3H]TdR and liquid scintillation spectrometry was used to determine the incorporation of [3H]TdR into DNA counting of 6-thioguanine (TG)-resistant cells. The ratio between the number of labeled cells in the Pb2+ treated group (T) and in the control group (C) was calculated. When the cells exposed to Pb2+ 6 mumol.L-1 for 4 h, the T/C ratios reached 1.75 (scintillation, S), and 2.07 (autoradiography, A) in human and 1.37 (S), and 1.77 (A) in rat cells. A positive relation existed between the concentration of Pb2+ and mutagenicity. Lead should be considered as a weak mutagen in human and rat keratinocytes. PMID- 8352009 TI - Effects of mebendazole, albendazole, and praziquantel on succinate dehydrogenase, fumarate reductase, and malate dehydrogenase in Echinococcus granulosus cysts harbored in mice. AB - Echinococcus granulosus cyst wall possess high biochemical activities of malate dehydrogenase (MD) and fumarate reductase (FR), but low activity of succinate dehydrogenase (SD), suggesting that the cyst wall may utilize a partial reverse tricarboxylic acid cycle. When infected mice were given intragastrically with mebendazole, 25-50 mg.kg-1.d-1, albendazole 300 mg.kg-1.d-1 or praziquantel 500 mg.kg-1.d-1 for 7-14 d, no apparent effects on SD and FR activities of the cyst wall were found, while the MD activity was suppressed by all the 3 drugs, the inhibition rates being 34.6-61.6%, 59.8%, and 50.6%, respectively. The results suggested that MD may not be an important target for the antihydatidosis drugs. PMID- 8352010 TI - [Promoting effect of panaxatriol ginsenoside on gene expression of human interleukin-1]. AB - Effect of panaxatriol ginsenoside (PG) on interleukin-1 (IL-1) gene expression was studied by using wheat germ extract (cell-free translation system) and IL-1 bioassay. The results showed that IL-1 production increased by 40% (487-682 U.ml 1) at maximum during cell culture (0-84 h) after PG (10 micrograms.ml-1) was added to phytohemagglutinin (PHA, 50 micrograms.ml-1) stimulated lymph node cells. Meanwhile, IL-1 mRNA from PHA combined with PG stimulated lymph node cells translated 39.5% more IL-1 than that of PHA-stimulated cells at maximum (2500 3489 U/mg RNA). PMID- 8352011 TI - [Assay of negative inotropism of bepridil on isolated guinea pig left atrial myocardium by simulating constant rate of absorption and elimination]. AB - The pharmacodynamic characteristic of negative inotropic effect of bepridil on isolated guinea pig cardiac atrium was conducted by gradient perfusion with constant rate of bepridil ranging from 0-20 mumol.L-1 and inverse, simulating a fixed pharmacokinetic parameters of K(a) and K(e), respectively. A counter clockwise hysteresis loop of negative inotropism of bepridil was presented. Fixing Cp, T, and E by pharmacokinetics/pharmacodynamics (PK/PD) non-parameter model, the hysteresis loop was collapsed in figure plotting C(e) against E. The estimated K(eo) = 0.03 +/- 0.023 h-1, an apparent T1/2 of pharmacological effect was measured, and about 80-fold as long as the pharmacokinetic T1/2. It was suggested that the long-lasting effect of bepridil was partly due to the slow elimination rate from the effect compartment. PMID- 8352012 TI - [Effects of furyl-dihydropyridine on action potential ventricular myocardium of rabbit in vivo and isolated guinea pig left atrium in vitro]. AB - Effects of furyl-dihydropyridine (FDP) on action potential of rabbit ventricular myocardium in vivo were observed with floating microelectrode technique. FDP 0.5 mg.kg-1 i.v. increased APD30 from 104 +/- 7 to 127 +/- 7 ms, APD90 from 146 +/- 10 to 177 +/- 9 ms (P < 0.01, n = 7), decreased the heart rate from 230 +/- 18 to 203 +/- 20 bpm (P < 0.05). Nifedipine (Nif) 0.5 mg.kg-1 i.v. reduced APD and increased the HR in rabbit. In guinea pig left atrium, FDP and Nif decreased the APD, the effects of acetylcholine to shorten the APD was antagonized by FDP 1 mumol.L-1. In rabbit's sinoatrial nodes, FDP 0.5, 1 mumol.L-1 also suppressed the APA and increased the spontaneous sinus cycle length (SCL) and APD50. These results indicate that FDP may inhibit the Ca2+ and K+ currents of myocardium. PMID- 8352013 TI - [Cardioprotection of 2-[p-(dimethylamino)styryl]pyridine methiodide against ischemic damage and myocardial lipid peroxidation]. AB - Mice were injected ip DSPM 1 or 3 mg.kg-1 3 h prior to a subcutaneous injection of isoproterenol (Iso) 20 mg.kg-1 once daily for 2 d. Iso induced reductions of Se-glutathione peroxidase (Se-GSH-PX), superoxide dismutase (SOD) activities, and an increase of malondialdehyde (MDA) content in myocardium. DSPM 1 or 3 mg.kg-1 significantly abated reduction of Se-GSH-PX activity and decreased MDA production and DSPM 3 mg.kg-1 also abated reduction of SOD activity in the hearts from Iso treated mice. The changes of above indices were in accordance with those of myocardial ultrastructure and creatine phosphokinase (CPK) concentration in serum. The results indicate that DSPM has a protective effect on myocardial ischemic injury probably by inhibiting oxygen free radicals and subsequent lipid peroxidation. PMID- 8352014 TI - [Distribution of 14C labeled at dioxopiperazine or methyl morpholine group of probimane by whole body autoradiography]. AB - Probimane (AT-2153) is a new anticancer compound. It was first developed in this Institute. It is effective against mouse tumors S37, S180, Lewis lung carcinoma, L1210 and human pulmonary adenocarcinoma heterotransplanted into nude mice. In the present work, 14C was labeled at central dioxopiperazine or methyl morpholine group of probimane 120 mg.kg-1 was injected iv in mice bearing Lewis lung carcinoma by whole body autoradiography. The results showed that probimane was broken into at least two parts: a central part and a methyl morpholine group. The central part of compound hardly penetrated through the blood-brain barrier, but accumulated in the urinary bladder. The methyl morpholine group showed a high affinity to tumor tissue and accumulated in spleen, bone and liver. PMID- 8352015 TI - [First-pass effect of dauricine]. AB - The first-pass effect of dauricine (Dau) was compared with that of lidocaine (Lid) by measuring the ventricular fibrillation threshold (VFT) and dauricine plasma concentration in rats or rabbits. After forelimb or mesenteric vein (imv) infusion of Dau at a rate of 1 mg.kg-1 x min-1 in rats, the VFT were 1.64-3.17 or 1.60-2.11 V, respectively. In the case of Lid at 2.5 mg.kg-1 x min-1, the VFT were 1.69-4.79 or 1.67-2.80 V, respectively, after ear vein (iev) or imv infusion of Dau at a rate of 0.5 mg.kg-1 x min-1 in rabbits, the VFT were 6.50-12.14 or 5.81-7.43 V, respectively. Plasma Dau concentration through iev infusion was significantly higher than that through imv route. As the dose of imv infusion increased, AUC of Dau showed a nonlinear increase. The results suggested that Dau showed a considerable first-pass effect, which was dose-dependent. PMID- 8352016 TI - [Distribution of harringtonine positively and negatively charged liposome in rat tissues]. AB - Distribution of harringtonine positively and negatively charged liposome (HL(+), HL(-)) and harringtonine free drug (FH) in rat tissues were measured by HPLC. Their LD50 in mice were compared. The results showed that distribution of HL(+), HL(-), In vivo may be changed, that the amount of HL(+), HL(-) was increased in the liver, lung, and spleen and in these tissues it was 2-30-fold higher than that of HF after iv 2 h. HL(+), HL(-) may aid to permeate through the blood brain, blood-testicle barrier, and to reduce acute lethal toxicity. Areas under the time curve of HL(+), HL(-) in brain and testis within 2 h were 2-4.5 times as much as those of HF. There were significant differences in the fate between negatively and positively charged liposomes in vivo. PMID- 8352017 TI - [Alpha-adrenoceptor stimulation mediated positive chronotropic effect in isolated right heart atria of normotensive and SHRsp rats]. AB - Concentration-dependent positive chronotropic response to phenylephrine (Phe) mediated by alpha 1-adrenoceptor in isolated normotensive and SHRsp rat right atria was determined under normal or depressed beat rate by stimulation of cholinergic M-receptor. The spontaneous beat rate was increased from 223 +/- 18 to 271 +/- 16 bpm by Phe 100 mumol.L-1 in the presence of propranolol 1 mumol.L 1. When the basal rate was lowered by stimulation of cholinergic M-receptor with carbachol, PE-induced increment of beat rate was enhanced to 101 +/- 23 bpm, accompanied by an increase of the force of contraction from 45 +/- 14% to 125 +/- 56% (vs control response). However, beta-adrenoceptor mediated positive chronotropic effect was attenuated in the presence of carbachol, and no positive inotropic effect was detected. PE-induced increase in beat rate in SHRsp (31 +/- 9 bpm) was lower than that in WKY (41 +/- 10 bpm). After pretreatment with carbachol, Phe caused increments in beat rate in SHRsp and WKY were 70 +/- 18 bpm and 114 +/- 17 bpm, respectively. It is suggested that in SHRsp, the function of cardiac alpha 1-adrenoceptor is lower than that in WKY. PMID- 8352018 TI - [Effects of protein kinase C activator and inhibitor on release of tumor necrosis factor from mouse peritoneal macrophages]. AB - The effects of protein kinase C (PKC) activator 1-O-tetradecanoylphorbol-13 acetate (TPA) and inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and quercetin were studied on release of tumor necrosis factor (TNF) from mouse peritoneal macrophages primed with Propionibacterium acnes (PA). The results showed that TPA (1-100 ng.ml-1) and lipopolysaccharides (LPS) (1-100 ng.ml-1) induced the release of TNF from PA-primed mouse peritoneal macrophages in dose- and time-dependent manners in vitro, and the effects of TPA and LPS were inhibited by H-7 (12.5-100 mumol.L-1) or quercetin (6.25-25 mumol.L-1) in a dose dependent manner. After ip H-7 (50 mg.kg-1), LPS-induced release of TNF in vivo decreased significantly. These results suggest that PKC may play a critical role in release of TNF from PA-primed macrophages. PMID- 8352020 TI - [Blocking effect of anisodamine on acetylcholine receptor channels]. AB - Anisodamine, an analog of atropine, was isolated first in China. Patch-clamp technique was used to study the inhibitory effect of anisodamine (Ani) on acetylcholine receptor on the membrane of muscle innervated by neuron. Neural tube in embryo of Xenopus laevis were cultured. By whole-cell clamp and outside out patch, we found that the inhibitory effect of Ani was obvious on both miniature end-plate currents (MEPC) and single channel. This effect was reversible and the minimal concentration for complete inhibition was 60 mumol.L 1, vs 1 and 0.5 mmol.L-1 for atropine and scopolamine, respectively. Our results indicate that Ani blocks both M-ACh and N-ACh receptors. PMID- 8352019 TI - [Protective effects of nicorandil on action potentials in anoxia and reoxygenated ventricular myocardium of guinea pig]. AB - Standard microelectrode techniques were used to study the effects of nicorandil (500 mumol.L-1) on action potentials in anoxia and reoxygenated ventricular myocardium of guinea pig. The main results: (a) Nicorandil shortened the action potentials duration (APD) and increased the ratio of effective refractory period (ERP) to APD90 (ERP/APD90). It did not cause significant changes in resting potential (RP), the maximal rate of rise of phase 0 (Vmax) and action potential amplitude (APA); (b) Exposure of the preparation to anoxic conditions (hypoxia, acidosis, glucose deprivation, and hyperkalemia) for 20 min, resulted in a marked depolarization of RP, a shortening of APD, reductions of APA and Vmax, and an increase in the ratio of ERP/APD90; (c) Nicorandil did not produce any additional effect on these parameters during anoxia except aggravated shortening of APD; (d) The changes of action potential parameters during anoxia were all completely reversed when the preparation was reoxygenated in the absence of the drug for 20 min. In the presence of the drug, however, APD was only partially reversed; (e) Nicorandil decreased the incidence of abnormal automaticity occurring during reoxygenation from 14/16 to 4/16. It is concluded that nicorandil antagonizes the cellular mechanisms which underlie the reoxygenation arrhythmias and prevent the reoxygenation-induced arrhythmias. PMID- 8352021 TI - Combination of HPLC and 252-Cf plasma desorption mass spectrometry for identifying composition of ginseng tinctures. AB - The 252-Cf plasma desorption mass spectrometry (252-Cf PDMS) determination or confirmation of the ginsenoside saponins has been proposed to investigate the composition of high performance liquid chromatography (HPLC) peaks of ginseng tinctures and galenic preparations. That ionization technique is well suitable for the analysis of natural mixtures of these saponins. The 252-Cf PD mass spectra of standard ginsenosides Rb1, Rb2, Rc, Re, Rg1, Rd, NG-R2, Z-R1 contain the peaks of two types of ions, namely, molecular adduct ions (MAI) and aglycone ions. By mass the latter may be referred to either protopanaxadiol or protopanaxatriol. The masses of MAI and aglycone ions are determined by the carbohydrate chains. The collected HPLC fractions of P ginseng tincture can be tested for content of ginsenosides. After studying two MAI peaks from the 252-Cf PD mass spectra of the basic ginsenosides, an example of distinction between two galenic preparations from different Panax has been shown. PMID- 8352022 TI - Dopaminergic influence on the excitability of antidromically activated Renshaw cells in the lumbar spinal cord of the rat. AB - The interaction between dopaminergic and cholinergic systems in the mammalian central nervous system, which is thought to have important implications in the pathophysiology of major extrapyramidal disorders, has never been adequately demonstrated in vivo. Renshaw cell burst responses to single electrical shocks to lumbar ventral roots in spinalized and decerebrated rats were studied. In this monosynaptic cholinergic pathway, apomorphine, a dopaminergic receptor agonist, inhibited whereas the D2-antagonist sulpiride facilitated the burst responses. The mutual antagonism of the two drugs and the depression coupled with the faster decay of post-tetanic potentiation of Renshaw cells by apomorphine demonstrate the involvement of presynaptic D2-receptors through which dopamine can modulate acetylcholine-mediated central synaptic transmission in vivo. The study also provides further evidence for the involvement of the spinal cord in extrapyramidal disorders. PMID- 8352023 TI - Membrane potential oscillations and corticothalamic connectivity in rat associational thalamic neurons in vitro. AB - Thalamic relay neurons were recorded from the dorsolateral and lateroposterior nuclei of the rat thalamus in a superfused explant preparation. The mean membrane potential of these cells was -67 +/- 7 mV, input resistance 114 +/- 31 M omega and spike amplitude 75 +/- 6 mV. Low-threshold slow membrane potential oscillations (1-4 Hz) were present in about 46% of the neurons. They occurred either spontaneously or following a membrane potential perturbation. In a subpopulation of cells, we also observed a high-threshold membrane oscillation when cells were depolarized above -45 mV. This oscillation consisted of bursts of low-amplitude spikes interrupted by rhythmic after-hyperpolarizations. Stimulation of the corticothalamic pathway elicited prolonged inhibitory postsynaptic potentials in associational thalamic neurons. In the presence of picrotoxin, corticothalamic input evoked prominent excitatory postsynaptic responses that showed marked short-term synaptic plasticity. Our results suggest that associational thalamic neurons maintained in vitro have a strong tendency to exhibit membrane oscillations. In addition, they receive a direct excitatory cortical input that remained functional in explant preparation. PMID- 8352024 TI - An indifference point for electrical impedance in humans. AB - Regional electrical impedance was used over eight sections of the human body (two thoracic; one abdominal; two thigh; two around the knee; and one lower leg) to determine the volume indifference point during passive head-up tilt in eight subjects. Head-up tilt was performed in 10 degrees increments from 0 degree to 60 degrees over 6 min. Electrical impedance increased over the thorax in proportion to the head-up tilt angle, while abdominal impedance did not change significantly, and over the thigh and the lower leg it decreased with increasing head-up tilt angle. No change in electrical impedance was noted just above the knee, and electrical impedance just below the knee decreased only marginally. Results demonstrate minimal fluid accumulation around the knee during head-up tilt. Furthermore, in humans the electrical impedance and therefore probably the volume indifference point is positioned between the umbilicus and crista iliaca. PMID- 8352025 TI - Effect on renin release of inhibiting renal nitric oxide synthesis in anaesthetized dogs. AB - Nitric oxide plays an important role in the regulation of basal renal blood flow. This study was performed to examine whether selective inhibition of renal nitric oxide synthesis affects renin release in vivo. Accordingly, in six barbiturate anaesthetized dogs renin release was examined before and after intrarenal infusion of the selective inhibitor of nitric oxide synthesis, NG-nitro-L arginine (NOARG). NOARG was infused into the renal artery to yield a renal arterial blood concentration of 0.4 mumol ml-1. NOARG did not change systemic arterial blood pressure and glomerular filtration rate, but reduced basal renal blood flow by 26 +/- 2%. Urine flow, sodium and potassium excretion were reduced after inhibition of renal nitric oxide synthesis. Basal renin release (3 +/- 2 micrograms AI min-1) was not altered by NOARG infusion (1 +/- 1 micrograms AI min 1). To stimulate renin release the renal artery was constricted to a renal perfusion pressure of 50 mmHg. At this perfusion pressure infusion of NOARG reduced renin release significantly from 48 +/- 11 micrograms AI min-1 to 14 +/- 4 micrograms AI min-1. In conclusion, inhibition of renal nitric oxide synthesis reduces basal renal blood flow and reduces renin release stimulated by renal arterial constriction. These findings indicate that renal nitric oxide modulates both renal blood flow and renin release in vivo. PMID- 8352026 TI - Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans. AB - Effects of the GABAergic drug diazepam (0.15 mg kg-1, i.v.) on cardiovascular and endocrine responses to 50 degrees head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1,10) = 6.45; P < 0.03). After 42 +/- 4 min of sustained tilt with saline (control) and 47 +/- 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2-3-fold increase in plasma ACTH, beta endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance. PMID- 8352027 TI - Rhythmic contractions of isolated small arteries from rat: influence of the endothelium. AB - Small arteries of the mesenteric arcade from Wistar rats display rhythmic oscillations superimposed on the tonic contractile response when exposed to submaximal doses of noradrenaline. We have previously shown that mechanical removal of the endothelium abolishes these oscillations. In the present study different methods to eliminate or modify the influence of the endothelium were used in order to further characterize the mechanisms behind rhythmic contractions in these vessels. Endothelium was removed either mechanically or chemically by perfusing the vessels with 0.3% CHAPS. The absence of functional endothelium enhanced noradrenaline sensitivity and simultaneously abolished oscillations in tension and membrane potential, but did not affect resting membrane potential. The rhythmic activity was also reduced or abolished by exposure to haemoglobin, methylene blue, LY83583 or L-NNA. Indomethacin and propranolol were without effect. Sodium nitroprusside or the permeant analogue of cyclic GMP, 8-bromo cyclic GMP, restored rhythmic activity in precontracted endothelium-denuded vessels. The data suggest that release of nitric oxide from the endothelium, and subsequent generation of cyclic GMP in the smooth muscle, activates oscillations in membrane potential and tension; the oscillator itself appears to be located within the smooth muscle cells. PMID- 8352028 TI - Vascular effects of endothelin-1 in the cat; modification by indomethacin and L NAME. AB - Intravenous infusion of endothelin-1 (ET-1) in the cat, 60 pmol x kg body wt-1 x min-1 for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 +/- 4.8 mmHg (n = 6; P < 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70-80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18-23%. Pre-treatment with indomethacin or a combination of indomethacin and L-NAME caused vasoconstriction in many tissues and modified the responses to ET-1 in a variable way, suggesting that normally, ET-1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues. Intracerebroventricular infusion (i.c.v.) of ET-1, 10 pmol x kg body wt-1 x min-1, caused an increase in MAP of 79 +/- 11 mmHg (n = 6; P < 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60-80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response. Our results indicate that in many tissues the vasoconstrictive effect of ET-1 is influenced by indomethacin- and L-NAME sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion. PMID- 8352029 TI - Effect of catecholamines on the ventricular myocyte action potential in raised extracellular potassium. AB - We describe the relationship between catecholamines and raised extracellular potassium ([K+]o) on action potential parameters and calcium currents in isolated ventricular myocytes of the guinea-pig and relate these findings to the problem of understanding how the heart is protected from exercise-induced hyperkalaemia ([K+]a up to 8.5 mM). Action potential duration (APD90), amplitude and upstroke velocity were recorded in stimulated (2Hz) guinea-pig ventricular myocytes using whole-cell patch electrode recordings (37 degrees C). Cells were superfused with normal K+ Tyrode and with raised K+ Tyrode in the presence of either noradrenaline, adrenaline or raised calcium. Inward calcium current was measured using voltage clamp. Raised K+ (8, 12, 16 mM K+ Tyrode) caused a significant (P < 0.01) depolarisation, shortened the APD90 and decreased the action potential amplitude and upstroke velocity. In raised K+ Tyrode addition of noradrenaline (0.08-0.1 microM) or adrenaline (0.1-0.2 microM) increased action potential amplitude (P < 0.01), APD90 (P < 0.01) and upstroke velocity (P < 0.01) (measured only in 16 mM K+ Tyrode). In 12 mM K+ Tyrode raised Ca2+ (5-6 mM) increased action potential amplitude (P < 0.05) and shortened APD90 (P < 0.05). Addition of NA (0.08-0.1 microM) increased the inward Ca2+ current. All effects were fully reversible. In raised [K+]o increases in catecholamines and [Ca2+]o cause changes in action potential parameters that would be expected to maintain propagation of the cardiac action potential in the whole heart. Thus, in the ventricular myocyte the increase in conductance to Ca2+ caused by catecholamines may be one factor that is important in minimising the potentially adverse effects of exercise induced hyperkalaemia. PMID- 8352030 TI - Increased technetium uptake is not equivalent to muscle necrosis: scintigraphic, morphological and intramuscular pressure analyses of sore muscles after exercise. AB - A scintigraphic technique employing technetium pyrophosphate uptake was used to identify the area of skeletal muscle damage in the lower leg of four runners 24 h after an ultramarathon footrace (160 km). Most of the race had been run downhill which incorporated an extensive amount of eccentric work. Soreness was diffuse throughout the posterior region of the lower leg. In order to interpret what increased technetium uptake reflects and to express extreme endurance related damages, a biopsy was taken from the 3-D position of abnormal uptake. In addition, intramuscular pressures were determined in the deep posterior compartment. Scintigraphs revealed increased technetium pyrophosphate uptake in the medial portion of the gastrocnemius muscle. For 3698 fibres analysed, 33 fibres (1%) were necrotic, while a few other fibres were either atrophic or irregular shaped. A cluster of necrotic fibres occurred at the fascicular periphery for one subject and fibre type grouping occurred for another. Ultrastructural analysis revealed Z-line streaming near many capillaries and variously altered subsarcolemmal mitochondria including some with paracrystalline inclusions. The majority of the capillaries included thickened and irregular shaped endothelial cells. Intramuscular pressures of the deep posterior compartment were slightly elevated (12-15 mmHg) for three of the four subjects. Increased technetium uptake following extreme endurance running does not just reflect muscle necrosis but also subtle fibre abnormalities. Collectively, these pathological findings are attributed to relative ischaemia occurring during the race and during pre-race training, whereas, intramuscular pressure elevations associated with muscle soreness are attributed to mechanical stress caused by extensive eccentric work during the race. PMID- 8352031 TI - Muscle strength and serum testosterone, cortisol and SHBG concentrations in middle-aged and elderly men and women. AB - Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44-57; n = 9), F50 years (range 43-54; n = 9), M70 years (range 64-73; n = 11) and F70 years (range 63-73; n = 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 +/- 452 N in M50 was greater (P < 0.05) than that of 2627 +/- 752 N recorded for F50 as well as the force of 2787 +/- 843 in M70 was greater (P < 0.001) than that of 1849 +/- 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.01) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r = 0.66; P < 0.01) and in the elderly subjects (r = 0.69; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352032 TI - Prodromal contractions and contractility in the feline bladder. AB - In the cat there are at least two distinct contractile states of the bladder during urine storage, one when prodromal contractions are present and one when non-micturating contractions are present. It is proposed that prodromal contractions are myogenic. This proposition was examined by comparing prodromal contractions before and after hypogastric nerve section as well as comparing prodromal contractions with the contractions that remain after sectioning of the hypogastric nerves. Key contraction characteristics, such as amplitude, maximum gradient and the variance of the intercontraction interval were not significantly changed by hypogastric nerve section, providing volume effects were corrected for, which suggested that prodromal contractions have a myogenic origin. PMID- 8352033 TI - An approach for measurement of tension transient responses of smooth muscles during their spontaneous contractions. PMID- 8352034 TI - Intracellular carbonic anhydrase activity and its role in GABA-induced acidosis in isolated rat hippocampal pyramidal neurones. PMID- 8352035 TI - Acute otitis media in adults: a report from the International Primary Care Network. AB - BACKGROUND: Of 22 million visits annually to United States physicians for acute otitis media, almost 4 million are by patients 15 years old or older. Yet the clinical spectrum and variables related to recovery have not been reported for adults. METHOD: Data originated from 3224 primary care patients with acute otitis media, of whom 500 were 15 years old or older, who were enrolled in a prospective study in eight countries. At the initial visit, history, symptoms, physical findings, and treatment were recorded. At a 2-month follow-up visit, changes in treatment and recovery were recorded. RESULTS: Compared with children, adults sought care more quickly after symptom onset; were more likely to have had a tonsillectomy or adenoidectomy; and were more likely to complain of ear pain, decreased hearing, sore throat, and ear discharge. Children were more likely to have a history of recent upper respiratory tract infection, serous otitis media, and ear tubes; symptoms of fever, diarrhea, and vomiting; and tympanic membrane findings of redness, bulging, and ear tubes in place. History of reduced hearing, allergy, prophylactic antibiotics, and tympanic membrane findings characterized as opaque or dull, fluid, draining pus, perforation, and not visualized were equally frequent in both age groups. For adults, neither type nor duration of antibiotic affected outcome. Patients receiving antibiotics had lower rates of recovery than those who did not. The likelihood of a poor outcome increased with an increasing number of past episodes of acute otitis media and with increasing age. CONCLUSION: Although history and symptoms differ in adults and children, the similarity of tympanic membrane findings is consistent with previous reports of a similar bacterial spectrum in both groups. Recovery is related more to individual patient characteristics and history than to antibiotic therapy. Adults have an increased rate of poor outcome at 2 months compared with children. PMID- 8352036 TI - Rate of anabolic-androgenic steroid use among students in junior high school. AB - BACKGROUND: Anabolic-androgenic steroid use has become an increasingly large problem. Studies document steroid use in high-school students, but not students in junior high school. We surveyed 7th-grade students to assess rate of use and knowledge about steroids. METHODS: Seventh-grade students completed a 22-question survey instrument that addressed previous steroid use, knowledge about the effects of steroids, other previous substance abuse, and demographic data. The one-sided Z test was used for statistical analyses. RESULTS: There were 4.7 percent of the male students and 3.2 percent of the female students who admitted to using steroids [corrected]. Those more likely to have tried steroids included African-Americans (P < 0.05), 15-year-olds (P < 0.05), football players (P < 0.025), wrestlers (P < 0.005), and past users of alcohol (P < 0.005) or tobacco (P < 0.005). There were significant differences between steroid users and nonusers in knowledge about the effects of anabolic-androgenic steroids on the body: steroid users knew less than nonusers. CONCLUSION: The establishment of steroid use in junior high school should cause physicians to seek signs or history of steroid use, especially in patients who are members of groups more likely to use them. In addition, physicians should initiate dialogue about steroids with patients before they are likely to have tried them. PMID- 8352037 TI - Seroprevalence of human immunodeficiency virus among family practice outpatients. AB - BACKGROUND: Because the human immunodeficiency virus (HIV) is extremely heterogeneous in its impact on various subpopulations, it is important to carry out HIV seroprevalence studies in different subpopulations using standardized techniques. The present study is the first to report seroprevalence rates of HIV in family medicine outpatient populations. METHODS: To estimate the prevalence and demographic distribution of HIV, 3874 sera samples were collected anonymously at six family medicine clinics in San Bernardino County during a 1-year period. RESULTS: Fifty-nine (1.52 percent) of the sera samples were confirmed HIV positive. Of the 59 HIV-positive patients, 43 were visiting the clinic for HIV related reasons. Excluding these 43 cases, and adjusting for age and race using the county population as a standard, the overall rate of HIV infection was 0.45 percent. The 16 HIV-positive patients who visited the clinics for reasons unrelated to HIV were between the ages of 20 and 59 years, with the 30- to 39 year-old age group having the highest prevalence (1.4 percent). Seroprevalence was eight times higher for men than women (chi 2 = 14.3, P = 0.0002), and rates for African-Americans (0.85 percent) were two to three times higher than for Hispanics (0.40 percent) and whites (0.25 percent). CONCLUSIONS: Results of this study are consistent with and support findings from previous surveys of more general populations in the western United States. There are approximately 7800 HIV-infected persons residing in San Bernardino County, and an estimated $796 million will be required to treat these individuals. PMID- 8352038 TI - Silver acetate mouth spray as an aid in smoking cessation: results of a double blind trial. AB - BACKGROUND: We studied the use of an aversive technique to improve the outcome of smoking-cessation efforts. We hypothesized that a silver acetate mouth spray, which produces a strong aversive taste when cigarettes are smoked, would increase the quit rate among smokers. METHODS: Our study was a double-blind, placebo controlled trial that was carried out in a private family practice office in an urban area. We studied 42 smokers, who were recruited by advertisement and who were motivated to quit by self-report. They were randomly assigned active spray or placebo spray; all were given a written list of behavioral suggestions. The spray was to be used every 2 hours for 3 weeks during which time the subjects were to keep diaries of cigarette smoking and spray use. Biochemical measures (salivary thiocyanate and cotinine) were recorded at entry, at 3 weeks, and at 3 months. RESULTS: Thirty smokers completed the study. No differences were found between the two groups in quit rate or number of cigarettes smoked. CONCLUSIONS: Silver acetate aversive spray did not increase quit rate among motivated smokers. PMID- 8352039 TI - Gender of physicians and patients and preventive care for community-based older adults. AB - BACKGROUND: This study was undertaken to determine whether the gender of patients and physicians is a significant factor in deciding which older adults are offered preventive care. METHODS: A survey of medical records of ambulatory patients older than 60 years was performed in the practices of 210 physicians. Documentation of influenza vaccine, rectal examination, fecal occult blood test, Papanicolaou smear, pelvic examination, breast examination, mammogram, and pneumococcal vaccine was recorded, and rates of compliance were evaluated by sex of patient and physician. RESULTS: The medical records of 3327 patients were surveyed. Men were given influenza and pneumococcal vaccines more frequently than women. Among physicians, women physicians were more likely to give influenza vaccine (P = 0.003) and to check for fecal occult blood (P < 0.001). No significant difference was found between men and women physicians in the frequency of doing Papanicolaou smears, breast examinations, rectal examinations, and mammograms. CONCLUSIONS: While a difference in practice patterns was found between men and women physicians, most of the variance in compliance with preventive care guidelines was unexplained by the gender of physicians and patients. Matching of physician and patient by sex did not predict improved preventive care, indicating that other factors are involved in the failure to provide adequate primary preventive care to the ambulatory elderly. PMID- 8352040 TI - Women and HIV. AB - BACKGROUND: Infection with the human immunodeficiency virus (HIV) has emerged as a major health problem for women in the United States. Family physicians can play an important role in the detection and care of HIV-infected women. METHODS: The epidemiology and natural history of HIV infection in women were reviewed. Articles were selected by a computer MEDLINE search. RESULTS: HIV infection is now a leading cause of morbidity and mortality among young women in the United States, particularly women of racial and ethnic minorities. Most cases of acquired immunodeficiency syndrome (AIDS) in women occur as a result of injection drug use or heterosexual transmission. Based on limited information, women and men appear to have similar AIDS-defining conditions. Gynecologic problems are common in HIV-infected women. Pregnancy does not seem to be affected by early HIV infection, but women with advanced disease might be at increased risk for obstetric complications. CONCLUSIONS: More women need to be included in natural history studies and clinical drug trials. Early awareness of HIV infection and better access to health care services are required to improve the treatment and survival of HIV-infected women. PMID- 8352041 TI - Obstetric care in family practice residencies: a national survey. AB - BACKGROUND: Supervision of obstetric care by family practice faculty increases the likelihood that family practice residents will choose to practice obstetrics. METHODS: A survey instrument was developed to obtain information about practice faculty and the educational setting in which residents learn family physician obstetric care. Questionnaires were sent to all family medicine residency directors and all full-time family physician faculty. RESULTS: Two hundred eighty four program directors and 1396 faculty members responded. The mean percentage of recent graduates estimated to be practicing obstetrics was 30 percent. Factors independently associated with an increased likelihood of resident graduates practicing obstetrics included supervision of resident deliveries by family physicians, increasing number of family practice center deliveries, regional differences, and availability of training to perform Cesarean sections. Sixty four percent of the responding family physician faculty were currently supervising deliveries, but only 5 percent had Cesarean section privileges. Seven percent of the faculty reported denial of obstetric privileges. Eighty-nine percent of all respondents supported the mandatory inclusion of obstetrics in family medicine residencies. CONCLUSIONS: Residency programs in family practice can increase the number of their graduates practicing obstetric care by focusing on the family physician supervision model, faculty development that supports this model, and clinical privileges of faculty. PMID- 8352043 TI - Family practice and the health care system. Implications of health reform for family practice. PMID- 8352042 TI - Vomiting as a manifestation of borderline personality disorder in primary care. AB - BACKGROUND: Patients with borderline personality disorder often are found and treated in psychiatric settings following episodes of self-mutilation, such as wrist-slashing. Family physicians care for many patients with borderline personality disorder, but in primary care settings wrist-slashing or other physical mutilation is a less common presenting problem. Frequently these patients complain of such symptoms as nausea and vomiting that do not so obviously suggest psychopathology. METHODS: Three primary care patients with borderline personality disorder in whom episodic vomiting was the chief complaint are presented. Hypotheses from the literature about the neurobiology of vomiting and self-mutilation are discussed. RESULTS: Vomiting is a primary care analogue of self-mutilation in some patients with borderline personality disorder. CONCLUSIONS: Family physicians should include careful history taking to corroborate other features of borderline personality disorder in evaluating patients with persistent, episodic vomiting. Obtaining a history of early sexual abuse or chronic interpersonal problems as an adult should not only mitigate the compulsion for extensive, costly, and invasive gastrointestinal system evaluations in such patients, but also suggest more effective treatment strategies. PMID- 8352044 TI - Salicylate-induced pulmonary edema: a complication of chronic aspirin therapy. PMID- 8352045 TI - Patient awareness of and attitudes toward physician board certification. PMID- 8352046 TI - Profile of full-time family practice faculty with private practice experience. PMID- 8352047 TI - Family medicine in Korea. PMID- 8352048 TI - A good death is hard to find: preliminary reports of a hospice doctor. PMID- 8352049 TI - Lessons from the International Primary Care Network. PMID- 8352050 TI - Answers in search of questions. PMID- 8352051 TI - Physicians' role in health care reform. PMID- 8352052 TI - Effectiveness of cough syrups. PMID- 8352054 TI - Unsolicited gifts from pharmaceutical companies. PMID- 8352055 TI - Techniques of meta-analysis. PMID- 8352053 TI - Family physicians and clinical ethics. PMID- 8352056 TI - In-hospital cardiopulmonary resuscitation. PMID- 8352057 TI - Obscure gastrointestinal bleeding. PMID- 8352058 TI - Fracture care. PMID- 8352059 TI - AIDS case definition. PMID- 8352060 TI - Calcium retention and hormone levels in black and white women on high- and low calcium diets. AB - Black-white differences in calcium metabolism are sought because they may reveal why blacks have higher bone mass than whites. Comparative studies of calcium absorption in blacks and whites are not available. In this study, we compare fractional calcium retention, an index of calcium absorption, and calcium regulating hormone levels in black and white women on a high-calcium diet and after adaptation to a low-calcium diet. A total of 30 healthy women (15 black and 15 white) had measurements of fractional 47Ca retention and calcium regulating hormone levels after 8 weeks on a 2000 mg calcium diet and, subsequently, after 1, 2, 4, and 8 weeks on a 300 mg calcium diet. By 2 weeks after the diet change, fractional 47Ca retention, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] had reached a plateau at higher levels, urine calcium at a low level, and serum calcium at the same level (repeated-measures ANOVA). Fractional 47Ca retention, serum calcium, and PTH were similar on both diets in blacks and whites. Blacks had higher levels of 1,25-(OH)2D on both diets (e.g., 125.1 +/- 53.5 SD versus 73.4 +/- 19.0 pmol/liter, P = 0.003 on low-calcium diet) and a greater increase in 1,25-(OH)2D after the diet change (33.9 +/- 30.1 SD versus 11.8 +/- 17.9 pmol/liter, P = 0.021). Serum phosphorus was lower in blacks throughout. For hormone levels and fractional calcium retention to stabilize after a diet change, 2 weeks was needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352061 TI - Alkali absorption and citrate excretion in calcium nephrolithiasis. AB - The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins). PMID- 8352062 TI - Dual-energy x-ray absorptiometry of the rat: accuracy, precision, and measurement of bone loss. AB - Dual-energy x-ray absorptiometry (DEXA) is now an established method of measuring bone mineral density (BMD) in humans. We have applied the technique to measuring BMD in the rat. The short-term precision of the technique was assessed by calculating the BMD coefficient of variation at the rat spine (1.20%), total femur (0.52%), proximal femur (1.16%), midfemur (1.00%), distal femur (0.96%), and proximal tibia (2.2%). The long-term precision of femoral measurements in rat cadavers over a 4 week period was 0.72% for the total femur and 1.2% for the distal femur. The accuracy of the technique was assessed by comparing DEXA measured bone mineral content (BMC) in vitro and in vivo with ashed BMC. Results indicated a highly significant positive correlation between in vitro DEXA measurements and ash BMC (r = 0.99) and between in vivo DEXA measurements and ash BMC (r = 0.89). The ability of the technique to detect bone loss was assessed at the femoral site by comparing the BMD of ovariectomized (OVX) and sham-operated rats at baseline and at a 1 month follow-up. There was no significant difference in BMD between the groups at baseline. However, at 1 month follow-up the OVX group showed a significant (p < 0.001) decline in BMD at the distal femur (-8.6%) and in the total femur (-4.8%) compared with sham-operated rats. A comparison of retired breeder female rats with age-matched nulliparous rats indicated that the BMD of retired breeder rats was significantly lower than that of virgin females at all femoral sites (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352064 TI - Prevalence of vertebral fracture in women and the relationship with bone density and symptoms: the Chingford Study. AB - A population survey was performed to estimate the prevalence of vertebral fractures in women aged 45-69 and to determine their relationship to bone density and symptoms. Subjects were 1035 women aged 45-69 (mean 55.4 years, response rate 77%) from the age-sex register of a large 11,000-person general practice in Chingford, London. Thoracic and lumbar spine x-rays were read by a semiautomated quantitative method. Vertebral fractures were diagnosed using a variety of morphometric methods, including a new method we recently developed and the published methods of Melton and Eastell. These methods all detect abnormal ratios between anterior, central, or posterior vertebral height and between observed posterior vertebral height and values predicted from the posterior height of adjacent vertebrae. Bone mineral density (BMD) of lumbar spine L1-4 and neck of femur was measured by dual-energy x-ray absorptiometry (DXA). Using our method, 147, 14.2% (95% CI 12.0-16.2%) of the 1035 women, had minor fractures (at least two vertebral ratios 2-2.99 SD below the mean) and 20, 1.9% (95% CI 1.2-3.0%) of the total, had severe fractures (at least two ratios more than 3 SD below the mean). In the 147 women with minor fractures, bone density of the spine was not significantly lower than in the other 868 women, and reported back pain or loss of height was no more common. Women with multiple minor fractures did have lower bone density, by 0.4 SD. In the 20 women with severe fracture, bone density was significantly lower, by 0.6 SD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352063 TI - Bone and mineral metabolism in the androgen-resistant (testicular feminized) male rat. AB - Androgens have important effects on bone in vivo, possibly by direct activation of the androgen receptors in osteoblasts. To test this hypothesis, calcium homeostasis, bone mass, and bone turnover were evaluated in mature (4-month-old) androgen-resistant (testicular feminized, TFM) male rats. Data were compared with data from both female and male littermates of the same age and strain. Compared to normal males, TFM had similar serum testosterone, twofold higher estradiol and estrone, and sixfold higher androstenedione concentrations. Compared to normal females, TFM rats showed lower estradiol but also elevated concentrations of androstenedione and estrone. Despite similar free 1,25-(OH)2D3 concentrations, both TFM and male rats maintained higher serum calcium and phosphate concentrations than their female littermates. Serum IGF-I concentrations in TFM rats were decreased compared to male rats (-12%) or female rats (-27%). Serum osteocalcin concentrations, however, were twofold higher in TFM rats than in females but not significantly different from males. Femoral length, diameter, and cortical thickness were intermediate between those of males and females. The cancellous bone density of the femur and cancellous bone volume of the proximal metaphysis of the tibia, however, were not significantly different between groups. The ash weight of the tibia was also not significantly different, and the ash weight of the four distal lumbar vertebrae ranged between male and female values. Bone mechanical properties as measured by torsional strength and energy absorption of the femur were lower in TFM than in females but not different from males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352065 TI - Effects of transforming growth factor beta 1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells. AB - Proteoglycans synthesized by osteoblasts are incorporated into bone matrix and thought to play a role in bone metabolism. Transforming growth factor (TGF) beta affects the synthesis of matrix proteins, including proteoglycans, in various stromal cells, and proteoglycans, especially decorin, are associated with matrix collagen. In the present study, the effects of TGF-beta 1 and L-ascorbate, a factor essential for collagen synthesis, on the synthesis and distribution of proteoglycans were examined using murine osteoblast-like MC3T3-E1 cells. TGF-beta 1 stimulated the synthesis of proteoglycans in MC3T3-E1 cells. Among various proteoglycans, the synthesis of decorin was preferentially enhanced by TGF-beta 1, and the effect was more pronounced on secreted decorin compared to that associated with the cell/matrix layer. TGF-beta 1 also stimulated the initiation and elongation of the dermatan sulfate glycosaminoglycan chain, resulting in a larger molecular size of decorin. TGF-beta 1 influenced the synthesis of a heparan sulfate proteoglycan only slightly. L-ascorbate had no effect on the synthesis of proteoglycans, but increased those associated with the cell/matrix layer. Furthermore, when L-ascorbate was added to the culture along with TGF-beta 1, the percentage of proteoglycans associated with the cell/matrix layer increased from 25.8 +/- 1.0 to 41.0 +/- 0.5%. These data demonstrate that TGF beta 1 markedly stimulates the synthesis of proteoglycans, especially decorin, mainly as a secreting form, that the accumulation of decorin into matrix is enhanced by L-ascorbate, and that the effects of TGF-beta 1 and L-ascorbate are additive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352066 TI - Estrogen does not restore bone lost after ovariectomy in the rat. AB - We recently found that 17 beta-estradiol (E2) not only suppresses bone resorption but also stimulates bone formation in the cancellous bone of female rats. This raises the possibility that E2 treatment might restore the bone lost after ovariectomy in the rat. To test this, 13-week-old rats were ovariectomized (ox). After a further 13 weeks the animals were injected with E2 (4 mg or 40 micrograms/kg daily), human calcitonin (hCT) (3 IU/kg daily), (3-amino-1 hydroxypropylidene)-1-bisphosphonate (AHPrBP) (0.3 mg/kg twice per week), or a combination of E2 with hCT or AHPrBP, for 8 weeks. The bone volume at the tibial metaphysis of ox animals was approximately 40% of that of sham-operated controls at the end of the experiment. Although the bone volume of ox rats treated with E2 and/or hCT or AHPrBP was slightly higher than that of untreated ox rats, the increase was not significant. Neither E2 alone nor a combination of E2 with hCT or AHPrBP was associated with a higher bone volume than hCT or AHPrBP alone, suggesting no effect of E2 beyond that of inhibition of bone resorption. Histodynamic indices of bone formation were increased in untreated ox rats compared to controls but suppressed in E2-treated, hCT-treated, and AHPrBP treated animals. These results emphasize the similar responses of rat and human bone, both of which not only show bone loss with estrogen deficiency, preventable by estrogen administration, but also show an inability of estrogen to restore bone lost as a result of estrogen deficiency. PMID- 8352067 TI - Passive immunization with anti-parathyroid hormone-related protein monoclonal antibody markedly prolongs survival time of hypercalcemic nude mice bearing transplanted human PTHrP-producing tumors. AB - Malignancy-associated hypercalcemia is mainly caused by excessive production of parathyroid hormone-related protein (PTHrP) by the tumor. Using anti-PTHrP-(1-34) monoclonal murine antibody (anti-PTHrP MoAb), we studied whether repeated injection of the homologous antibody would continuously decrease the serum calcium concentration in hypercalcemic nude mice bearing transplanted human PTHrP producing tumors, leading to prolongation of their survival time. Daily SC injections of anti-PTHrP MoAb decreased the serum calcium concentration almost to within the normal range in nude mice bearing transplanted human PTHrP-producing tumors (T3M-1, EC-GI, PC-3, and FA-6) but not in a nude mouse bearing a transplanted parathyroid carcinoma. The antibody did not affect FA-6 tumor growth either in vitro or in vivo. Pancreatic carcinoma cells (FA-6), which caused the most severe hypercalcemia, were inoculated into 6-week-old nude mice. When severe hypercalcemia (approximately 19 mg/dl) had developed, daily SC injection of anti PTHrP MoAb was started. Within 18 days of this time point, all untreated tumor bearing mice (n = 10) died of hypercalcemia and cachexia, whereas all the treated mice (n = 10) showed an increase in body weight and survived for at least 25 days. Histologic examination of the treated mice revealed a marked decrease in osteoclastic bone resorption, without toxicologic findings in the kidney and liver. These results suggest that passive immunization against PTHrP can continuously ameliorate the hypercalcemia and markedly prolong the survival time of severely hypercalcemic, tumor-bearing mice. If a human monoclonal antibody against PTHrP-(1-34) could be developed, then passive immunization would be potentially one of the most effective therapies for patients with malignancy associated hypercalcemia due to excessive production of PTHrP. PMID- 8352068 TI - Bone density and body composition on the Pacific rim: a comparison between Japan born and U.S.-born Japanese-American women. AB - Bone mineral density (BMD) of total body, spine, and proximal femur and the percentage of body fat in 151 U.S.-born Japanese-American women and 137 Japan born immigrant Japanese-American women living in San Diego, California were measured using dual-energy x-ray absorptiometry. These data were compared with unpublished data from Japanese women obtained in previous studies in Hamamatsu, Japan. The age-adjusted BMD for the spinal level, femoral neck, Ward's triangle, trochanter, and total body, respectively, of U.S.-born Japanese-American women were 10.2, 9.8, 9.9, 9.2, and 2.7% higher than those of native Japanese women. The U.S.-born Japanese-American women had significantly higher body fat than immigrant Japanese-American women. Furthermore, the immigrant women had higher BMD and higher body fat than their native Japanese counterparts; however, no significant total-body BMD differences were found among the three groups after age, height, and weight were adjusted. The U.S.-born Japanese-American women had BMD values equivalent to those of white normals at the spine and femur. Significant life-style differences between U.S.-born and immigrant Japanese American women were noted. Weight, exercise, early menarche, and years of lifetime estrogen exposure correlated positively with BMD. The significant negative correlates of BMD were age, smoking, and percentage of body fat. Our study presents data suggesting that immigration to the United States has produced a higher BMD in Japanese-American women that is attributable to changes in life style and diet. PMID- 8352069 TI - Effects of combined prostaglandin and alendronate treatment on the histomorphometry and biomechanical properties of bone in ovariectomized rats. AB - Prostaglandin E2 (PGE2) has been shown to stimulate both bone resorption and formation in experimental animals, leading to augmentation of trabecular and cortical bone. The amino bisphosphonate alendronate (ALN) is a potent inhibitor of bone resorption. The objectives of this study were to examine if PGE2 stimulation of bone formation was dependent on bone resorption and if the bone accrued as a result of PGE2 treatment contributed to bone strength. The 48 female Sprague-Dawley rats were assigned to six groups as follows: five groups (8/group) were ovariectomized at the age of 6 months. One group was sacrificed 2 months later to establish baseline conditions, and four groups were treated for 25 days with (1) vehicle, (2) PGE2 at 3 mg/kg/day, (3) ALN sc at 0.8 micrograms/kg/day, and (4) PGE2 + ALN at the respective doses. The sixth group served as nonovariectomized untreated controls. Histomorphometric analysis of 6-10 microns thick tibial sections after in vivo fluorochrome double labeling showed that treatment with PGE2 alone increased endocortical mineral apposition rate and bone formation rate, stimulated production of bone trabeculae in the marrow cavity, and increased cortical porosity. Combined ALN + PGE2 treatment prevented the resorption induced by PGE2 but not the stimulation of bone formation on endocortical and periosteal surfaces and resulted in a significant increase in cortical thickness. Consistent with these observations, the femoral midshaft tested to failure in three-point bending showed a significant increase in strength in the PGE2 + ALN group (181 +/- 15 N) compared to time 0 controls (145 +/- 23 N) or to the ovariectomized vehicle-treated group (141 +/- 28 N).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352070 TI - Urinary hydroxypyridinium crosslinks of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis. AB - Estrogen deficiency-induced bone loss has been associated with accelerated bone turnover. Levels of some biochemical markers, such as serum osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline (OHP), have been shown to be related to the rate of bone turnover. They may therefore be useful in identifying the individual at risk for osteoporosis and monitoring the efficacy of the treatment. Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP. To evaluate the effects of menopause, osteoporosis, and estrogen replacement on the excretion of these new markers, we measured the levels of PYD and DPD and other biochemical markers of bone turnover in four groups of women, premenopausal healthy (PRE), postmenopausal healthy (POST), postmenopausal osteoporotic (UTO), and postmenopausal osteoporotic with estrogen treatment (ETO). Significant increases in PYD, DPD, BGP, TRAP, and OHP were found in POST and UTO groups compared with PRE. These increases were blunted by estrogen treatment when the levels of each of the markers returned to PRE levels. When comparing POST and UTO groups, significant increases were observed in UTO only for PYD, DPD, and urinary calcium but not for OHP, BGP, or TRAP. With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO. Indices of bone formation covaried with markers of bone resorption in the total population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352072 TI - 15th annual meeting of the American Society for Bone and Mineral Research. Tampa, Florida, September 18-22, 1993. Abstracts. PMID- 8352071 TI - Effects of high extracellular calcium and strontium on inositol polyphosphates in bovine parathyroid cells. AB - The addition of Ca2+ or a variety of divalent cations increases intracellular Ca2+ in parathyroid cells and suppresses secretion. Since 1,4,5-inositol trisphosphate (IP3) and 1,3,4,5-inositol tetrakisphosphate (IP4) mediate Ca2+ mobilization in other systems, we examined high Ca(2+)- and Sr(2+)-induced accumulation of IP3 and IP4 isomers by anion-exchange HPLC and measured 1,4,5-IP3 mass in parathyroid cells. Raising extracellular [Ca2+] from 0.5 to 3.0 mM increased 3H-1,4,5-IP3 within 5 s, which was confirmed by mass measurements. 3H 1,3,4-IP3 rose gradually by 10 s and increased for 60 s after the addition of Ca2+. Although we detected no change in 3H-1,3,4,5-IP4, the increase in 3H-1,3,4 IP3 suggests that 3H-1,3,4,5-IP4 was being formed. The addition of 4 mM SrCl2 produced similar changes in 1,4,5-IP3, which were confirmed by mass assay. 3H 1,3,4,5-IP4 did not change. However, Sr2+ induced a gradual increase in 3H-1,3,4 IP3, which remained above control levels for 5 minutes. Isotopic labeling studies in this system may underestimate changes in 1,4,5-IP3 mass, but both mass and radioisotopic analyses indicate that high extracellular Ca2+ and Sr2+ stimulate substantial increases in 1,4,5-IP3 without significant accumulation of 1,3,4,5 IP4. These studies suggest a role for 1,4,5-IP3 in intracellular Ca2+ mobilization by divalent cations in parathyroid cells. PMID- 8352074 TI - [Present state of myopia studies]. PMID- 8352073 TI - Spring meeting of the British Geriatrics Society. 15-17 April 1993, Glasgow. Abstracts. PMID- 8352075 TI - [An electron microscopic histochemical study on the localization of sialic acids in human trabecular meshwork]. AB - The localization of sialic acids in human trabecular meshworks of normal eyes, primary open angle glaucoma (POAG) eyes, congenital glaucoma eyes, and juvenile glaucoma eyes was investigated using biotinyl lectin (LPA, SSA, MAM) and avidin gold electron microscopic histochemistry. Gold particles were detectable in fine fibrils underneath Schlemm's canal and collagen fibers of normal, POAG, congenital glaucoma, and juvenile glaucoma eyes equally. Many gold particles were detected especially in fine fibrils and basal membrane (compact tissue) 3 microns underneath Schlemm's canal. The present study indicated that extracellular matrices of congenital glaucoma and juvenile glaucoma contained sialic acids and that this may be related to the ocular hypertension of these diseases. PMID- 8352077 TI - [Participation of procoagulant activity of cultured rabbit lens epithelial cells in fibrin formation]. AB - To clarify the participation of the lens epithelial cells in the postoperative fibrin formation in cataract surgery, the generation of procoagulant activity (PCA) by cultured rabbit lens epithelial (RLE) cells was investigated. PCA was detected in the homogenates of RLE cells cultured for three hours. PCA was increased approximately three- to four-fold by lipopolysaccharide (LPS) stimulation in a dose dependent manner. Treatment of the RLE cells with Concanavalin A resulted in a decrease of PCA. PCA of the RLE cells was not observed in Factor VII deficient plasma, as a standard tissue factor (TF). Parallelism was recognized between the dose response regression lines for the PCA in the RLE cells and standard TF. These results suggest that the PCA in the RLE cells is similar to TF, which has glycoprotein as an active site and requires coagulation factor VII. Some arachidonic acid metabolic cascade inhibitors which show an inhibitory effect for fibrin formation in vivo reduced the generation of PCA by the RLE cells in vitro. The activation of arachidonic acid cascade followed by the generation of PCA in the RLE cells may participate in postoperative fibrin formation. PMID- 8352076 TI - [THC-YAG laser sclerostomy ab externo in monkey eyes]. AB - THC-YAG laser sclerostomy was performed in 7 eyes of 6 monkeys. The 26-gauge optic probe, which delivers energy perpendicularly to the long axis of the probe, was inserted through a 1-mm conjunctival stab incision, 6-7 mm away from the limbus, and the probe tip was positioned at the sclerostomy site. Pulse energy of 80 mJ or 100 mJ was used with a repetition rate of 5 pulses per second. Total energy levels to produce a new outflow pathway ranged from 1.2 to 6.6 J (2.8 +/- 1.2 J). After the surgery, 5-fluorouracil (0.1 mg daily) was injected subconjunctivally for 7 days, and intraocular pressure measurements and ophthalmic examination were performed for 4 weeks. Eyes were enucleated just after surgery or 1 week or 4 weeks after surgery. Intraocular pressures in operated eyes at 1 week and 4 weeks after surgery were reduced to 7-10 (9 +/- 1.2) mmHg, and 0-11 (3.5 +/- 4.3) mmHg, respectively, in comparison with intraocular pressures in nonoperated eyes. Histological examination revealed that the sclerostomy hole with a diameter of 150 microns just after surgery had narrowed at 1 week, and was closed by subconjunctival proliferative tissues at 4 weeks after surgery. PMID- 8352078 TI - [Retinal ischemic changes in diabetic rats treated with pancreatic islet transplantation beneath the renal capsule]. AB - The effect of pancreatic islet transplantation beneath the renal capsule on retinal and choroidal structure was studied using Lewis rats. Rats were divided into 3 groups: an untreated diabetic group induced by intravenous injection of streptozotocin 65 mg/kg; an islet transplanted group 1 month after induction of diabetic state; and an untreated control group. Whole retinochoroidal units were examined by light and electron-microscopy. In 6 out of 9 cases in the transplanted group, the retina showed marked destructive changes in the outer layer including pigment epithelial cells and vacuolization of the inner layer 6 months after islet transplantation. Occlusion and fibrosis of the choriocapillaris adjoining the degenerated retina were also observed. Such changes were not observed in the other groups. On electron microscopy, occlusion of capillaries and destruction of endothelial cells were frequently found in the degenerated retina. These retinal ischemic lesions appear to be caused by microvascular obstruction. PMID- 8352079 TI - [Cytotoxic T lymphocyte activity after intravitreal inoculation of herpes simplex virus type I in mice]. AB - After inoculating mice with herpes simplex virus (HSV) by a corneal or intravitreal route, cytotoxic T lymphocyte (CTL) activity in the cervical lymph nodes and spleen was assayed. The spleen and cervical lymph nodes were removed at various points till 2 weeks after inoculation, and CTL activity was assayed in a groups: (A) mice intravitreally inoculated with HSV, and (B) mice with topical application of HSV. The reactivity of delayed type sensitivity was determined by the thickness of the mouse ear pinna on the 6th day in both groups. CTL activity in the spleen was at the same level in both groups. Up to 10 days after inoculation CTL activity in the cervical lymph nodes in group (A) was lower than in group (B). The reactivity of delayed type sensitivity in group (A) was lower than in group (B). These results indicate that an anterior chamber associated immune deviation (ACAID)-like phenomenon occurred after HSV inoculation into the vitreous cavity. PMID- 8352080 TI - [Volume measurement of the horizontal extraocular muscles using magnetic resonance imaging]. AB - The volume of the horizontal extraocular muscles of 11 normal adults and three patients with ophthalmoplegia was measured using magnetic resonance imaging (MRI). The MRI examinations were carried out with a Signa Advantage, 1.5 tesla superconductive magnetic system manufactured by General Electric. This method employs the spin echo technique with a 3.0 mm gapless slice, a 350 ms. repetition time, and a 17.0 ms. echo time. The MRI films were projected and magnified on Kent paper using an overhead projector. Then the shapes of the horizontal extraocular muscles were traced. The volume of the muscles was measured as the total weight of Kent papers which were cut out from muscle shapes in all the slices. The average volume of the normal medial and lateral rectus muscles was 690 +/- 87 mm3 and 734 +/- 77 mm3, respectively. Two cases with peripheral nerve palsy showed typical atrophy of the paretic muscles. A case with orbital myositis showed typical hypertrophy of the inflamed muscles. This measurement may prove useful in the analysis and evaluation of extraocular muscles, especially in ophthalmoplegia. PMID- 8352081 TI - [Plasma intramembrane structure of overaction of the inferior muscle in humans]. AB - We used the freeze-fracture method to compare the intramembrane structure of the plasma membrane in inferior oblique (IO) muscles from six strabismus patients with normal IO muscles. Inferior oblique myectomy provided us with small pieces of IO muscle from three patients with superior oblique paresis, and from one patient each with V-pattern exotropia, V-pattern esotropia, and V-pattern intermittent exotropia. Samples of normal IO muscle were obtained from two men, aged 33 and 73 years, within 24 hours of their death. The excised muscles were separated at their belly part into orbital and global layers, and small bundles of muscle fiber were fixed and freeze-fractured. The size of intramembrane particles (IMPs) did not differ significantly between normal and strabismus affected specimens (mean: 9.5 nm). The density of IMP in the 33-year-old man's sample ranged from 800 to 3300/microns2 with a mean of 1823/microns2, in the 73 year-old man's sample ranged from 100 to 2500/microns2 with a mean of 670/microns2, while in the affected tissues it ranged from 100 to 1000/microns2 with a mean 500/microns2. There were no significant differences in caveola size and density between normal and strabismus-affected IO muscles. PMID- 8352082 TI - [Treatment and prognosis of diplopia]. AB - The case notes of 341 patients who had consulted the Ocular Motility Clinic of Hyogo College of Medicine between 1986 to 1992 with a chief complaint of diplopia were studied. The recovery rates of diplopia from major causes were as follows: 72% of patients recovered from diplopia in oculomotor nerve palsy, 70% in trochlear nerve palsy and 71% in abducens nerve palsy. Various treatments were effective to eliminate the diplopia in 69% of patients with myasthenia gravis, 60% in Graves' ophthalmopathy, 78% in blowout fractures and orbital tumors. Pharmaceutical therapy was applied in 236 cases. In ocular motor nerve palsy oral prednisone gave a higher recovery rate than other medicines. The recovery rate of diplopia in medicinal therapy was 60% and it increased to 69% when combined with surgical treatment. We concluded that it is better to select the surgical treatment if the patient complains of diplopia after more than 6 months of conservative therapy. PMID- 8352083 TI - [Measurement of ocular position using Purkinje images. Part 1. A new measurement system]. AB - I developed a new system of measuring ocular position using the first and fourth Purkinje images. This method used two images which were reflected from the front surface of the cornea and the back surface of the lens. I got a cross line from the first Purkinje image by putting a cross lens filter in front of the infrared camera. When I superimposed the vertical line upon the fourth image, I could get the optic axis of the eye. In order to measure the ocular position, I measured the angle of the optic axis. The accuracy of this system was +/- 0.1 degrees and the maximum error was smaller than +/- 0.5 degrees. Measurements with this system were easily obtained from squint patients and correlated well with results from the prism cover test (R2: 0.941). This measurement system was more useful than the prism cover test because I was able to measure horizontal deviations more precisely. PMID- 8352084 TI - [Measurement of ocular position using Purkinje images. Part 2. The measurement of ocular position in subjects wearing spectacles]. AB - The first and the fourth Purkinje images are formed by the front surface of the cornea and the posterior surface of the lens. This measurement system is based on the principle of aligning one image with the other horizontally. It produces a precise measurement of the horizontal ocular position. I measured ocular position using this system when the subjects wore spectacles. The subjects gazed at a target position that was placed horizontally at 5 degrees intervals within a range of 25 degrees from the center to both sides. I analyzed the differences between the target position and the measurement data obtained by this system. The higher the refractive power of the lens the subjects wore, and the further the target position was from the center the greater were the differences between them. If the fixed target was placed within +/- 10 degrees, the difference was less than 0.5 degrees in all the spectacle lenses tested. I concluded that the measurements obtained with this system were useful even when the subjects wore spectacles. PMID- 8352085 TI - [The relationship between the developmental change in visual acuity measurements and change of refractive error in young infants]. AB - 219 normal infants aged 3 to 36 months were tested to investigate the relationship between the development of visual acuity and the change of refractive error. 17 infants were tested over a period of time. Visual acuity was assessed by Teller Acuity Cards (TAC), and refractive error was measured by an infrared video refractor (PR1000) without cycloplegics. The results were as follows. 1) The success rate of both tests in 3 to 6 month-old infants was higher than in infants aged 11 to 14 months and 23 to 36 months. 2) Visual acuity showed a rather slow development in infants aged 3 to 12 months. 3) With-the-rule astigmatism of 1 diopter (D) or more occurred with a high incidence in the 3 to 8 month old infants, and decreased with age. 4) The visual acuity in the infants with astigmatism was no different than in those without it. 5) The slow developmental curve of visual acuity measured in 3 to 12-month old infants was probably the result of psychological aversion to the TAC. PMID- 8352086 TI - [Corneal curvature of myopia]. AB - We classified myopia by total refractive error, measured the corneal curvature, and analyzed the relationship between the diopter value and corneal curvature in growing teen-agers and in adults in their twenties, whose myopic progress is presumed to have stopped. We adopted as the harmonic average the central 3.0 mm of the cornea. We also examined peripheral corneal curvature in upper side, lower side, temporal side and nasal side at about 4.5 mm and 6.5 mm diameter from the center. There was very little difference in the harmonic average of corneal curvature from -1D to -6D. Similarly, there was very little difference in the peripheral corneal curvature. The corneal curvature was larger from central to periphery in all directions. The upper side was larger than lower side and the nasal side was larger than the temporal side. We concluded that the refractive power did not depend on the corneal refractive power in mild to moderate myopic patients. PMID- 8352087 TI - [The shape of posterior staphyloma in high myopia]. AB - In 105 eyes of 68 highly myopic patients with focal chorioretinal atrophy in posterior staphyloma, the shape of the staphyloma and the process of backward elongation were studied. Indirect binocular ophthalmoscopy (and in some cases slit-lamp biomicroscopy of the fundus.) was used to observe the staphyloma. The results were as follows: 1) In 72.4% of all the eyes, patchy atrophy (part or whole) protruded or became dented in the staphyloma. The protrusion and the dent did not correlate with age. The refraction of eyes which had protruded patchy atrophy was significantly stronger than those which had dented patchy atrophy. The axial length of eyes which had protruded patchy atrophy was also significantly longer. 2) The protrusion and the dent were localized in patchy atrophy with a diameter of over 1.5 PD. 3) In 80.3% of peripapillary chorioretinal atrophic cases, atrophy protruded or became dented in the staphyloma. 4) In 43.8% the limits of the location of retinal blood vessels formed part of the borderlines of the staphyloma. 5) In 28.6%, steps were created in the staphyloma by the limits of the location of retinal blood vessels. As the staphyloma progresses, patchy atrophy, annular-type myopic crescents, and the location of retinal blood vessels influence the shape of the staphyloma. PMID- 8352088 TI - [Early change of visual function in high myopia--measured and analyzed by octopus automated perimeter]. AB - To evaluate the early changes of visual function in high myopic eyes, visual field examinations were performed using an Octopus 201 automated perimeter to 206 eyes of 120 patients. Corrected visual acuities were better than 0.8 and there were no abnormal findings except tigroid fundus change. 64 eyes of 38 patients were selected as a control group, whose refractive degrees were between +1.0D and -1.0D, corrected visual acuities were better than 1.0. The correlations of visual field changes with age, refractive degrees, axial length and sex were investigated. The total loss of high myopia group and the control group was compared, and changes in certain members of the high myopia group were followed up. The results were as follows: 1) Compared to the control group, the high myopia group had remarkably great loss. It revealed that the functional changes occurred already in the tigroid fundus stage. 2) Refractive degrees and axial length showed a significant positive correlation with total loss. This indicated that the refractive degrees and axial length played important roles in determining the visual field change of high myopic eyes. 3) Age and sex showed no statistically significant correlations with total loss. 4) The mean loss of the upper temporal quadrant and 11 degrees-20 degrees annular area were the largest. It appeared that the earliest changes in high myopia possibly began from the lower temporal region of the disc. 5) In the follow-up study, the loss increased persistently in the whole field, especially in the upper temporal and 11 degrees 20 degrees area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352089 TI - [A case of pleomorphic adenocarcinoma of the ciliary body]. AB - We performed local resection of a ciliary body tumor, which was diagnosed as pleomorphic adenocarcinoma arising from nonpigmented epithelium of the ciliary body. The patient was a 57-year-old male, and the tumor was found incidentally at an ophthalmologic examination. Since the possibility of malignant tumor could not be ruled out, local resection of the tumor was performed. The tumor developed from the pars plicata and the size was 5.5 x 6.0 x 7.5 mm. Histologically, the tumor cells displayed heteromorphism and revealed tubular and glandular structures which continued to the ciliary body epithelium. Melanin pigment was not observed, except in one small area of the tumor. The interstitium of the tumor tissue was stained with alcian blue, and a immunohistochemical study showed that tumor cells were positive for epithelial membrane antigen (EMA) and vimentin, but negative for S-100 protein and carcinoembryonic antigen (CEA). Electron microscopy revealed desmosomes between cells, and microvilli were observed at the margin of the glandular cavity structure. In this case, no severe complications occurred even after local resection and good visual function was maintained. PMID- 8352090 TI - Radiologists in the United States: demographic, professional, and practice characteristics. AB - OBJECTIVE: The purpose of this report is to present a statistical portrait of radiologists in the United States based on the 1990 American College of Radiology Manpower Survey. Unlike previous surveys, this survey included radiologists who were not members of the College and was thus more representative of all radiologists. (Approximately three quarters of radiologists are College members.) We examined how the demographic, professional, and practice characteristics of radiologists vary among major groups within the profession. MATERIALS AND METHODS: A stratified random sample of 2804 radiologists and nuclear medicine specialists was drawn from the American Medical Association Physician Masterfile, which is the most complete and extensive single source of information on physicians in the United States. Because the total numbers of female radiologists, nuclear medicine specialists, and radiologists less than 35 years old are relatively small, these groups were deliberately "oversampled" (hence the term stratified random sample) to ensure sufficient numbers of responses in these categories for meaningful analysis. A total of 1845 completed questionnaires were received, which yields a response rate of 68% if the questionnaires sent to invalid addresses are excluded. Responses were weighted to make the data representative of all radiologists, despite differences in sampling rates. RESULTS: Findings for professionally active radiologists who completed their training included the following: 94% were certified by the American Board of Radiology, 13% were women, 47% were less than 45 years old, fees for service were the primary remuneration for 62%, and 72% are in practices owned by physician members of the practice. By major activity in radiology, 69% were diagnostic radiology generalists; 11% were radiation oncologists; 18% were diagnostic radiology subspecialists; and 2% were nuclear medicine specialists. A breakdown by age indicated that the age group of radiologists less than 45 years old included more women, diagnostic subspecialists, and persons who had fellowship training than other age groups did. Percentages of diagnostic radiology generalists and solo practitioners were lower among younger radiologists. Radiation oncologists, compared with all others, were the most likely to practice solo or in small groups of two to four members. The subfields with the highest percentages (60% or more) of diagnostic radiologists reporting expertise or proficiency were CT, mammography, and sonography. Among radiologists who were retired, half had retired by the time they were 65 years old. However, a majority of radiologists 65-69 years old were still working, as were 40% of those 70-74 years old. CONCLUSION: The profession of radiology is changing, with more women, subspecialists, and fellowship-trained radiologists in younger age groups and fewer solo practitioners. Only a small percentage of radiologists are not board certified. Radiologists typically remain professionally active into their late 60s or even beyond. PMID- 8352091 TI - Plagiarism: what is it, whom does it offend, and how does one deal with it? AB - Academic plagiarism is a thorny ethical and practical problem. Perhaps readers have never personally encountered or recognized a case of plagiarism so its immediate interest and relevance may be obscure. A short case history may provide evidence that the issue of plagiarism is germane to the contemporary academic endeavor. A young university radiologist recognized his own writing in a professional journal under another's authorship, without attribution to himself, and had no idea what to do about it. He finally wrote to the author of the article who answered something to the effect that it was indeed a "remarkable coincidence" and that "great minds think alike." Unsatisfied with the response, he considered reporting the matter to the journal editor, but he was a junior faculty member while the plagiarist was a revered figure in his subspecialty. He chose not to pursue the issue further because he was afraid that the plagiarist would harm him professionally [1]. PMID- 8352092 TI - Imaging of suspected aortic dissection. PMID- 8352093 TI - Imaging to distinguish between viable and nonviable myocardium: pathophysiologic basis and importance of positron emission tomography. AB - One goal of strategies designed to restore nutritive perfusion in patients with left ventricular dysfunction attributable to coronary artery disease is salvage of reversibly ischemic myocardium in an effort to improve patients' left ventricular function, signs and symptoms, and survival. Accurate identification of patients likely to benefit from interventions such as coronary revascularization requires the differentiation of viable (reversibly dysfunctional) myocardium from nonviable (persistently dysfunctional) tissue. To date, no consensus has been reached regarding the best approach for achieving this differentiation. In this review, the pathophysiologic characteristics of viable and nonviable myocardium are summarized, and diagnostic methods that exploit these characteristics for the purposes of detecting viable myocardium are discussed. Emphasis is placed on approaches that use positron emission tomography because of its usefulness in quantifying those specific metabolic processes that support both tissue viability and the capacity for functional recovery. PMID- 8352094 TI - Clinical and videofluoroscopic evaluation of swallowing disorders. AB - Swallowing and feeding problems are common, particularly in elderly persons, and will be an increasing cause of disability as the geriatric population expands. Consequently, the need for clinical and radiologic examinations of patients who have swallowing problems will likely become commonplace. In this review, we define the problem confronting these patients, discuss the clinical and videofluoroscopic procedures used to examine patients with swallowing difficulty, and integrate the results of these examinations and their impact on feeding recommendations. PMID- 8352095 TI - Idiopathic laryngotracheal stenosis: radiologic findings. AB - OBJECTIVE: Acquired nonneoplastic laryngotracheal stenosis can be either focal or diffuse. Diffuse tracheal stenosis is caused by sarcoidosis, tuberculosis, histoplasmosis, relapsing polychondritis, tracheopathia osteoplastica, and Wegener's granulomatosis. Focal tracheal stenosis, on the other hand, usually results from placement of an endotracheal or tracheostomy tube or from previous neck trauma. At our institution, since 1971, we have seen 49 cases of focal laryngotracheal stenosis that could not be attributed clinically or histologically to any one of the aforementioned causes. The purpose of this study was to study the radiologic features of these idiopathic laryngotracheal stenoses. MATERIALS AND METHODS: A retrospective review of records showed that radiologic studies were still available in only 15 of the 49 patients with idiopathic laryngotracheal stenoses. All 15 patients had radiographs and plain tomograms, and one patient had a CT scan of the neck. Three radiologists reviewed all the images. RESULTS: The radiologic appearance was variable: the stenoses were from 2 to 4 cm long with a lumen between 3 and 5 mm in diameter at the narrowest portion. The narrowing was concentric and shaped like an hourglass in eight patients (53%) and was eccentric in the other seven (47%). The margins of the stenosis were smooth in nine patients (60%) and irregular and lobulated in six patients (40%). A dominant mass measuring approximately 1 cm in diameter was present in two patients (13%). No evidence of calcification or ossification was seen. CONCLUSION: Idiopathic laryngotracheal stenosis produces focal stenosis of the cervical part of the trachea, 2 to 4 cm long. The lumen is severely compromised, measuring no more than 5 mm in diameter at its narrowest portion. The stenosis can be concentric or eccentric and can have either smooth or lobulated margins. Special attention should be paid to the airways when chest radiographs of patients with a history of prolonged dyspnea and wheezing are reviewed. The prevalence of focal stenosis of the larynx and the upper part of the trachea due to tracheal intubation has declined since the introduction of low pressure, high-volume retention cuffs. Therefore, idiopathic laryngotracheal stenosis should be considered in the differential diagnosis in patients with focal narrowing of the airway. PMID- 8352096 TI - Diagnosis of diseases of the trachea and main bronchi: chest radiography vs CT. AB - OBJECTIVE: The purpose of this study was to compare the sensitivities and diagnostic accuracies of chest radiography and CT in the assessment of diseases of the trachea and main bronchi in regard to detection, evaluation of focal vs diffuse disease, separation of benign from malignant disease, and accuracy of diagnosis. MATERIALS AND METHODS: The chest radiographs and CT scans of 35 patients with proved diseases of the trachea and main bronchi and five control subjects were randomly assessed by two independent observers in a blind study. The diagnoses included 25 malignant and 10 benign conditions. The malignant lesions included 24 primary tumors and one metastatic melanoma. The benign lesions included two benign tumors, two tracheal stenoses, one focal amyloidosis, one tracheomalacia, and four miscellaneous diffuse abnormalities. The observers were asked to determine if an abnormality was present, to classify it as focal or diffuse and as benign or malignant, and to list the three most likely diagnoses. Sensitivities were compared by using the McNemar test. RESULTS: The sensitivity of both observers in detecting disease on the chest radiograph was 66%. The sensitivity on the CT scan was 97% for the first observer and 91% for the second observer (p < .01). Both observers were able to correctly classify the detected abnormalities as either focal or diffuse in 91% of cases on the chest radiographs and 97% of cases on the CT scans. The abnormalities were correctly classified as either benign or malignant in 78% of cases by both observers on the chest radiographs and in 85% and 78% of cases on the CT scans by the first observer and the second observer, respectively. The correct diagnosis was included in the list of the three most likely diagnoses in 61% of cases by both observers after reviewing the radiographs and in 56% of cases by one observer and 63% of cases by the other observer after reviewing the CT scans. CONCLUSION: CT is superior to chest radiography in allowing detection of abnormalities of the major airways. Both CT and chest radiography are accurate for differentiating focal from diffuse disease, but neither technique is accurate for distinguishing benign from malignant disease or for establishing a specific diagnosis. PMID- 8352097 TI - CT visualization of the major pulmonary fissures: value of 25 degrees cranially tilted axial scans. AB - OBJECTIVE: CT visualization of the major (oblique) pulmonary fissures is often hampered by partial volume effects of adjacent lung parenchyma. We attempted to improve visualization of the fissures by using 25 degrees cranially tilted axial scans. An initial in vitro study also was performed. MATERIALS AND METHODS: Both conventional and 25 degrees tilted axial CT scans were obtained in 40 adult patients. After scans with 2-mm collimation were obtained at 1 cm and 6 cm below the carina, the gantry was tilted 25 degrees cranially to be perpendicular to the plane of the major fissures, and scans with 2-, 5-, and 10-mm collimation were obtained at the same two levels. The appearance of the fissures was classified as linear opacity, band-like opacity, or avascular area for each lung at each level. RESULTS: On 2-mm conventional axial scans, the major fissures were seen as linear opacities in three to 23 patients (8-58%), as band-like opacities in 13-31 (32 78%), and as avascular areas in one to seven (2-18%). (Ranges indicate lowest and highest values when data for the two levels in the two lungs are grouped separately.) On 2-mm tilted scans, the ranges were 32-38 patients (80-95%), one to eight (2-20%), and zero to one (0-2%), respectively. The 2-mm tilted scans were significantly superior to the 2-mm conventional axial scans for showing the fissures (p < .01). Direct visualization as linear or band-like opacities was possible even on 10-mm tilted scans in 15-32 cases (38-80%). CONCLUSION: Our results show that visualization of the major fissure is improved when tilted CT scans rather than conventional axial scans are used. PMID- 8352098 TI - Lung cysts associated with Pneumocystis carinii pneumonia: radiographic characteristics, natural history, and complications. AB - OBJECTIVE: The purpose of our study was to characterize the radiographic features of thin-walled air-filled structures (cysts) related to Pneumocystis carinii pneumonia in a large series of patients, determine the natural history of the cysts, and test the hypothesis that the cysts are associated with an increased risk of pneumothorax. MATERIALS AND METHODS: Of 100 patients with proved pneumocystis pneumonia, 34 (34%) had cysts shown on chest radiographs. The size, number, and location of the cysts and their natural history and association with pneumothorax were determined. A control group consisting of a random sample of 30 patients was selected from the 66 patients who had pneumocystis pneumonia but no cysts to assess the frequency of pneumothorax in this population. RESULTS: Of 34 patients with cysts, 32 (94%) had multiple cysts that were 1.0-5.0 cm in diameter. Most cysts were in the upper part of the lungs. Most patients had complete or partial resolution of the cysts after the acute episode of pneumonia. Pneumothoraces occurred in 12 (35%) of the 34 patients with cysts, but in only two (7%) of the 30 who did not have cysts (p = .007). CONCLUSION: Cysts related to pneumocystis pneumonia are usually multiple, occur most often in the upper parts of the lungs, and tend to decrease in size or resolve after the acute stage of the infection. In patients with pneumocystis pneumonia, the prevalence of pneumothorax is significantly higher in those who have cysts than in those who do not. The cysts are similar to pneumatoceles and the high prevalence of pneumothorax may be due to the subpleural location of some cysts. PMID- 8352099 TI - CT diagnosis of superior vena cava syndrome: importance of collateral vessels. AB - OBJECTIVE: The purpose of this study was to evaluate the importance of collateral vessels in the CT diagnosis of superior vena cava syndrome. MATERIALS AND METHODS: Forty-seven patients with CT evidence of obstruction or compression of the superior vena cava or its major tributaries were included in this study. Contrast-enhanced CT scans had been obtained with a combined bolus and drip infusion technique. We evaluated the CT scans, with particular attention to the presence of collateral vessels (and if present, their location), without knowing the patients' clinical histories. On reviewing the patients' charts, we found 23 patients with signs or symptoms of superior vena cava syndrome. We then correlated the presence of collateral vessels with the presence of signs and symptoms of superior vena cava syndrome. To verify the frequency of visible collateral vessels in healthy subjects, we also evaluated CT scans of 50 control subjects who did not have mediastinal disease or signs and symptoms of superior vena cava syndrome. RESULTS: Collateral vessels were seen on CT scans in 24 patients. Among the 23 patients who had signs and symptoms of superior vena cava syndrome, 22 patients had CT scans that showed collateral vessels. Two cases were false-positive and one was false-negative. The presence of collateral vessels, regardless of the number and location of the vessels shown on CT scans, was highly accurate as a predictor of superior vena cava syndrome, with a sensitivity of 96% and a specificity of 92%. Collateral vessels were seen in three (6%) of the 50 control subjects. CONCLUSION: We conclude that the presence of collateral vessels is a highly sensitive and specific CT sign of superior vena cava syndrome. PMID- 8352100 TI - Solitary plasma cell tumor of the pleura manifested as massive hemothorax. PMID- 8352101 TI - Pulmonary strongyloidiasis: an unusual opportunistic pneumonia in a patient with AIDS. PMID- 8352102 TI - Arrhythmogenic right ventricular disease: MR imaging vs angiography. AB - OBJECTIVE: Arrhythmogenic right ventricular disease (ARVD) is increasingly found in young adults with ventricular arrhythmias and is characterized by ventricular tachycardia originating within the right ventricle and regional or diffuse abnormalities in the contraction of the right ventricle. Until now, the gold standard for the detection of global and regional abnormalities of the right ventricular wall has been angiography combined with biopsy. The purpose of the current study was to compare MR imaging with angiography for assessing the location and extent of morphologic and functional abnormalities in patients with ARVD. SUBJECTS AND METHODS: Electrocardiographically gated spin-echo and cine gradient-echo MR imaging of the heart was performed in 36 consecutive patients with biopsy-proved ARVD. Patients were prospectively separated into two groups according to the results of invasive electrophysiologic tests (18 with inducible ventricular tachycardia during invasive electrophysiologic studies [ARVD 1] and 18 without inducible ventricular tachycardia [ARVD 2]) and compared with 11 control subjects. Global and regional morphology and function of the right ventricle were assessed with MR imaging, and those findings were compared with angiographic findings. RESULTS: Right ventricular ejection fraction was significantly lower in patients with ARVD 1 than in patients with ARVD 2 or in control subjects. Regional abnormalities of the right ventricular wall also were more pronounced in patients with ARVD 1 than in patients with ARVD 2. Signal intensity increases corresponding to fatty replacement shown by biopsy were seen in 33% of patients with ARVD 1 and in 11% of patients with ARVD 2. Abnormal regions of the right ventricular wall seen on MR images corresponded to angiographic findings in 86% of patients. Comparison with control subjects showed that patients with ARVD 1 had a significant delay in diastolic relaxation of the right ventricle. CONCLUSION: Our results show that MR imaging can be used to assess morphologic alteration, tissue abnormalities, and global as well as regional dysfunction of the right ventricle in patients with ARVD. It may become a useful clinical tool for diagnosing and grading ARVD and a worthy substitute for angiography and biopsy in the follow-up of patients with ARVD. PMID- 8352103 TI - Aortic motion artifact simulating dissection on CT scans: elimination with reconstructive segmented images. PMID- 8352104 TI - Use of digital mammography in needle localization procedures. AB - OBJECTIVE: With digital technology, images can be displayed rapidly and manipulated. This study was undertaken to assess the duration and accuracy of needle localizations performed with digital vs film-screen technology. These two technologies also were compared with respect to radiation doses and ability to image a standard phantom. SUBJECTS AND METHODS: A prototype digital mammographic system with both a 512 x 512 matrix and a 1024 x 1024 matrix was evaluated by using the American College of Radiology mammography accreditation phantom, and these results were compared with testing done on commercially available, dedicated, analog mammography equipment. Duration, accuracy of needle placement, and number of exposures needed to perform localization were recorded for 157 consecutive needle localizations done with digital technology, and these results were compared with data collected from 103 needle localizations done with film screen technology. Another 33 localizations attempted with digital imaging were aborted because of technical factors. Average glandular doses were calculated for those women who had a compressed breast thickness of 4-5 cm. RESULTS: The time to complete needle localization was reduced by almost 50%, from 20 to 11 min, when digital technology was used. Because of the small (5 x 5 cm) field of view of the digital system, an additional mammogram obtained at the onset of the procedure was found to be helpful in localization, but otherwise the number of images was the same regardless of imaging receptor. Mean glandular dose was reduced by about 50% with digital imaging from 0.219 to 0.120 cGy. In those 17% (33/190) of needle localizations that could not be completed with digital imaging, failure was due to a variety of factors. Despite improved detectability of fibrils, specks, and masses on digital images, digital systems did not show some fine calcifications or soft-tissue masses during needle localizations. Difficulty in imaging lesions near the chest wall or in the axilla and the small field of view also caused procedures attempted with digital imaging to be aborted and completed with film screen systems. CONCLUSION: The time to complete needle localization was reduced by 50%, with a similar reduction in patients' radiation dose, when digital mammography was used. These findings should be applicable to stereotaxic procedures done with digital mammography. Factors limiting the use of digital mammography equipment included inability to image some fine calcifications and some masses, difficulty in imaging near the chest wall and in the axilla, and a small field of view. PMID- 8352105 TI - Splenic venous flow exceeding portal venous flow at Doppler sonography: relationship to portosystemic varices. AB - OBJECTIVE: The purpose of this study was to determine if the Doppler sonographic finding of hepatopetal flow in the splenic vein that exceeds hepatopetal flow in the portal vein is associated with portosystemic varices. MATERIALS AND METHODS: Sixty-four patients with chronic liver disease were studied retrospectively. In 32 patients, splenic venous flow exceeded portal venous flow (S > P group); in 32 patients, portal venous flow exceeded splenic venous flow (P > S group). All patients were evaluated with Doppler sonography and CT of the upper part of the abdomen. Upper endoscopy was performed within 3 months of sonography in 44 of the 64 patients. RESULTS: In the S > P group, mean splenic volume was significantly larger (p = .02) than in the other group. The prevalence of varices as determined by CT in the esophageal, coronary, and peripancreatic regions was also higher in this group (p < or = .01). When esophageal varices were present, they were judged on the basis of their CT appearance to be massive in 50% of the S > P group and in 0% of the P > S group. Upper endoscopy revealed esophageal varices in 92% of the S > P group and in 55% of the P > S group (p < .005). Bleeding esophageal varices were noted in 75% of the S > P group and in 30% of the P > S group (p < .01). CONCLUSION: Patients with chronic liver disease and the Doppler sonographic finding of splenic venous flow that exceeds portal venous flow have an increased prevalence of portosystemic varices, which tend to be larger and more likely to bleed. PMID- 8352106 TI - Transdiaphragmatic portosystemic shunt to the pericardiacophrenic vein. PMID- 8352107 TI - Segmental anatomy of the liver: utility of a nomenclature accepted worldwide. AB - A major use of imaging techniques in the preoperative evaluation of hepatic tumors is to help the surgeon determine the feasibility of hepatic resection. Although the segmental location of tumors is not the sole criterion for determining resectability, such information is crucial for the preoperative planning of the type of resection. PMID- 8352108 TI - An American's guide to Couinaud's numbering system. PMID- 8352109 TI - Hypereosinophilic syndrome: imaging findings in patients with hepatic involvement. AB - OBJECTIVE: Hypereosinophilic syndrome (eosinophilia without demonstrable cause) commonly involves eosinophilic infiltration of the liver and spleen, but few reports have described the imaging findings. Accordingly, we reviewed the imaging findings in five patients with this syndrome in whom the liver was involved. MATERIALS AND METHODS: Five patients who had hypereosinophilic syndrome with hepatic involvement were included in the study. The diagnosis of hepatic involvement was based on pathologic proof in two patients and on imaging and laboratory findings in the other three. Histologic examination of the hepatic lesions showed extensive eosinophilic infiltration in two patients and centrilobular necrosis in one. All patients had chest radiography, barium studies of the gastrointestinal tract, abdominal CT, and sonography. Four patients had hepatosplenic scintigraphy. All patients were followed up for 4-24 months. RESULTS: All patients had mild to marked hepatomegaly with multiple focal lesions. Focal lesions were detected on sonograms in three patients, on CT scans in four, and on scintigrams in three. On sonograms, the lesions were usually small (less than 2 cm in diameter), sharply or poorly defined nodules with varied echogenicity scattered throughout the liver. The lesions were hypodense with poorly defined margins on CT scans and appeared as variably sized areas of decreased radionuclide uptake on scintigrams. For each patient, the number, size, and shape of the lesions varied considerably from one imaging study to another. On follow-up studies 2-6 months after treatment, the appearance of the liver was normal. Other radiologic findings included transient pulmonary infiltrates (two patients), mild cardiomegaly (one patient), and mild lymphadenopathy (three patients). CONCLUSION: Hypereosinophilic syndrome is a cause of focal hepatic lesions seen on sonograms, CT scans, or scintigrams. The lesions are characterized by the varied appearance on the different types of images and the disappearance of the lesions with treatment. PMID- 8352110 TI - MR findings of multiple biliary hamartomas. PMID- 8352111 TI - Histoplasmosis of the colon in patients with AIDS: imaging findings in four cases. AB - OBJECTIVE: The purpose of this study was to describe and illustrate the radiographic findings of colonic histoplasmosis in patients with AIDS. SUBJECTS AND METHODS: Four HIV-positive patients were admitted because of fever, abdominal pain, tenderness, weight loss, and diarrhea. One patient had known disseminated histoplasmosis, one had esophageal moniliasis, and two had no other known opportunistic infections or tumors. All four patients had barium enemas, and two had abdominal CT examinations. The diagnosis was established via colonoscopic biopsy in three patients and with surgery in one patient. RESULTS: Barium enema in two patients showed separate, short, apple-core lesions in the transverse and descending colon. In one patient, a single lesion in the ascending colon mimicked colonic carcinoma. One patient had segmental involvement of the ascending colon, compatible with inflammatory bowel disease. CT examination revealed circumferential thickening of the wall of the colon with adjacent lymphadenopathy of mixed attenuation. Three patients responded to medical therapy, and one patient remained symptomatic and was found on a follow-up CT examination to have significant recurrence of retroperitoneal lymphadenopathy. CONCLUSION: Colonic histoplasmosis in patients with AIDS has protean radiographic features and can mimic colonic carcinoma. In these patients, histoplasmosis should be part of the differential diagnosis, particularly when several colonic lesions are detected, associated regional and retroperitoneal lymphadenopathy is present, and the patient is living or has lived in an endemic area. PMID- 8352112 TI - Imaging of peritoneal pseudocysts: value of MR imaging compared with sonography and CT. AB - OBJECTIVE: Peritoneal pseudocysts are created when fluid arising from the ovary is trapped by peritoneal adhesions. We studied the value of MR imaging, compared with sonography and CT, for detecting these abnormalities. SUBJECTS AND METHODS: Nine women, 27 to 49 years old, who had surgically proved peritoneal pseudocysts were included in the study. All nine patients were premenopausal, and eight had a history of pelvic surgery. All patients were examined with MR imaging and sonography, and five were also examined with CT. Imaging findings were analyzed and compared with the surgical findings. RESULTS: Sonograms in all nine patients showed a thick-walled cyst that contained focal echoes indicating nodules, making it difficult to differentiate these lesions from cystic ovarian tumors. In eight of the nine patients, the fluid in the pseudocysts had low signal intensity on T1 weighted MR images and high signal intensity on T2-weighted spin-echo MR images, suggesting that the fluid was serous. The pseudocyst had an irregular shape on MR images in seven patients and on CT scans in three patients. However, MR provided more information than CT did about the nature of the fluid within the pseudocyst. CONCLUSION: Our study suggests that MR imaging is more useful than sonography and CT for determining the characteristic findings of peritoneal pseudocysts. PMID- 8352113 TI - A bad case of medical jargon. PMID- 8352114 TI - Assessment of myometrial invasion by endometrial carcinoma: transvaginal sonography vs contrast-enhanced MR imaging. AB - OBJECTIVE: A prospective study was designed to compare transvaginal sonography with contrast-enhanced MR imaging to determine preoperatively the depth of myometrial invasion in patients with early-stage endometrial carcinoma. SUBJECTS AND METHODS: In 40 patients, findings on transvaginal sonograms, unenhanced T2 weighted MR images, and contrast-enhanced T1-weighted Mr images were compared with histologic findings. The depth of myometrial invasion was classified as stage E (tumor limited to endometrium, n = 12), stage S (superficial invasion: tumor invades up to 50% of the myometrium, n = 15), or stage D (deep invasion: tumor invades more than 50% of the myometrium, n = 13). RESULTS: Findings on transvaginal sonograms were accurate in 27 of 40 patients (accuracy, 68%); the depth of invasion was overestimated in five patients and underestimated in eight patients. The results of unenhanced T2-weighted MR images were accurate in 27 patients (accuracy, 68%), with four overestimations and nine underestimations. The results of contrast-enhanced T1-weighted MR images were accurate in 34 patients (accuracy, 85%), with five underestimations and one overestimation. In the assessment of each stage of myometrial invasion, the sensitivity and specificity of contrast-enhanced T1-weighted imaging were higher than those of T2 weighted MR imaging and transvaginal sonography. The false-positive diagnoses based on transvaginal sonograms and T2-weighted images, respectively, involved polypoid tumors (n = 4 and 2), distension of the endometrial cavity by pyometra (n = 2 and 1), the presence of myoma (n = 2 and 1), atrophy of the myometrium (n = 1 and 0), and poor tumor/myometrium contrast (n = 0 and 2). On contrast enhanced MR images, accuracy was influenced only in a case of polypoid tumor, because tumor, endometrial cavity, and myometrium were clearly distinguished and residual myometrium was clearly visualized. With all imaging techniques, false negative diagnoses were caused mainly by tumors with superficially spreading growth or microscopic invasion. With transvaginal sonography, infiltrative tumor also tended to be understaged (n = 3). CONCLUSION: Contrast-enhanced MR imaging is significantly superior to transvaginal sonography and unenhanced T2-weighted MR imaging for detecting myometrial invasion. PMID- 8352115 TI - Multilocular cyst of the kidney. PMID- 8352116 TI - Fast spin-echo MR images of the pelvis obtained with a phased-array coil: value in localizing and staging prostatic carcinoma. AB - OBJECTIVE: The fast spin-echo pulse sequence allows T2-weighted MR images to be acquired more rapidly than is possible with conventional spin-echo sequences, and phased-array coils can provide a higher signal-to-noise ratio than is possible with the body coil. The combination of these methods permits higher resolution images to be obtained with more signal averages despite shorter imaging times. In this study, initial technical comparisons designed to confirm the advantage of combining fast spin-echo pulse sequences with a pelvic phased-array multicoil were followed by an assessment of the value of these methods for the localization and staging of prostatic carcinoma. SUBJECTS AND METHODS: Seventy-one men with known (60) or suspected (11) prostatic carcinoma were imaged with T2-weighted fast spin-echo pulse sequences in the axial and coronal planes with a phased array of four surface coils (multicoil) for signal reception. Four of these men also were imaged with fast spin-echo sequences and the body coil, and six of these men also were imaged with T2-weighted conventional spin echo sequences and the multicoil; image qualities achieved with these techniques were compared. The use of IV glucagon (42 of 71 studies) before fast spin-echo sequences was correlated with the subsequent presence or absence of peristaltic artifacts on MR images. MR images were analyzed for the presence or absence of prostatic cancer in the right and left sides of the gland and for evidence of spread either through the capsule, into the seminal vesicles, or to lymph nodes or bone. Findings at MR imaging were compared with results of radical prostatectomy (20), lymph node dissection without prostatectomy (seven), and biopsy (67). RESULTS: Image quality obtained with the combination of the fast spin-echo sequence with the multicoil was judged superior to that obtained with either the conventional spin-echo sequence with the multicoil or the fast spin-echo sequence with the body coil. Significant motion artifacts were noted in 45% of studies (13/29) performed without glucagon vs 7% of studies (3/42) performed with glucagon. In the 58 patients for whom information concerning the location of tumor in either the right or left side of the gland was obtained from biopsy (39) or surgery (19), MR images allowed cancer to be detected with 89% sensitivity and 77% specificity. Among the 20 patients undergoing prostatectomy and seven others undergoing lymph node dissection, MR imaging permitted high accuracies in predicting involvement of the seminal vesicles (100%), local transcapsular spread (85%), and involvement of pelvic lymph nodes (85%). CONCLUSION: Fast spin-echo imaging with a pelvic phased-array multicoil provides high-resolution images of the prostate that may obviate an endorectal coil for the detection, localization, and staging of prostatic carcinoma. PMID- 8352117 TI - MR imaging of the ankle and foot: normal structures and anatomic variants that may simulate disease. AB - In the past, MR imaging of the ankle and foot has been performed by scanning both extremities simultaneously to provide a normal side for comparison. More recently, unilateral imaging with small local coils has been favored to maximize spatial resolution through use of small fields of view or large matrices. Such clarity of detail, however, demands a greater knowledge of normal anatomy and anatomic variants. We illustrate the MR appearances of a number of variants involving muscle, tendons, ligaments, and osseous structures of the foot and ankle. Familiarity with these findings is essential to prevent errors in the interpretation of MR images. PMID- 8352118 TI - Free vascularized fibular grafts: radiographic evidence of remodeling and hypertrophy. AB - OBJECTIVE: A study was undertaken to determine the growth potential and radiographic appearance of a free vascularized fibular graft as it responds to the mechanical and physiologic features of its new environment. MATERIALS AND METHODS: In a 10-year period, 30 patients underwent reconstruction of a large skeletal defect with a vascularized fibular graft. Radiographic studies were adequate for assessing sequential changes in 21 patients. Hypertrophy was evaluated by serial measurements of the periosteal and endosteal dimensions and was assessed with respect to age, sex, duration and location of the graft, the indication for reconstruction, and fixation apparatus. RESULTS: Hypertrophy of vascularized bone grafts is not rare. Among 21 vascularized fibular grafts, a measurable degree of hypertrophy was found in eight. Hypertrophy was caused by periosteal formation of new bone. The amount of hypertrophy could be considerable; in some cases it reached 2 cm of new cortical bone, resulting in an unusual radiographic appearance of marked cortical thickening. The amount of hypertrophy was greatest in young males, but was independent of diagnosis and site, and could be seen even in grafts bridged by metallic plates. CONCLUSION: Hypertrophy of vascularized bone grafts is a relatively frequent finding and has distinctive radiographic features. It is unclear why hypertrophy occurs to a much greater extent in some grafts than in others. PMID- 8352120 TI - Calcaneus as a site for assessment of bone mineral density: evaluation in cadavers and healthy volunteers. AB - OBJECTIVE: The value of calcaneal dual-energy X-ray absorptiometry for monitoring changes in bone mineral density has not yet been established. Accordingly, the focus of this study was to determine the usefulness of the calcaneus as the site for bone mineral density measurement with dual-energy X-ray absorptiometry. SUBJECTS AND METHODS: Dual-energy X-ray absorptiometry of the calcaneus was performed in 19 specimens derived from 11 cadavers and 337 healthy volunteers to assess accuracy, in vivo precision, and age-related changes in bone mineral density. We also compared calcaneal bone mineral density determined by dual energy X-ray absorptiometry with lumbar spine bone mineral density determined by dual-energy X-ray absorptiometry (L1-L4) or quantitative CT (L3). RESULTS: Studies of specimens showed that dual-energy X-ray absorptiometry had an error rate of 6%. In addition, strong correlations were found between bone mineral content and ash weight (r = .97, p < .0001) and between bone mineral density and ash density (r = .87, p < .0001). In vivo studies showed moderate correlations between calcaneal bone mineral density determined by dual-energy X-ray absorptiometry and lumbar spine bone mineral density determined by dual-energy X ray absorptiometry (men, r = .77, p < .0001; women, r = .76, p < .0001) and lumbar spine bone mineral density by quantitative CT (men, r = .68, p < .0001; women, r = .68, p < .0001). Calcaneal bone mineral density measured by dual energy X-ray absorptiometry and lumbar spine bone mineral density measured by quantitative CT continued to decrease throughout the postmenopausal period. However, lumbar spine bone mineral density determined by dual-energy X-ray absorptiometry did not show further decreases in subjects more than 70 years old. CONCLUSION: Taken together, these results suggest that the calcaneus can be used as an additional site for determining bone mineral density to assess osteopenia in patients when deformities of the spine make quantitative CT or other methods of density measurement impossible. PMID- 8352119 TI - Motion of the patella during walking: a video digital-fluoroscopic study in healthy volunteers. AB - OBJECTIVE: The alignment of the quadriceps muscle and patella suggests that the patella should deviate laterally out of the patellar groove as the quadriceps muscle contracts during walking. The surgical treatment of patellar subluxation has been based on this presumption. The purpose of this study was to determine the movements of the patella in relation to the other bones of the knee joint during normal walking. This is the first study we know of that uses radiographs to show these movements. SUBJECTS AND METHODS: Eight healthy adult volunteers with no previous complaints referable to the knee walked on a slowly moving treadmill while their patellae were imaged fluoroscopically in the anteroposterior plane with a Toshiba C-arm. Images were retrieved, transferred to radiographic film, and randomized to prevent the observers from knowing the order of images. The position of the patella was measured and plotted in relation to fixed points of the knee. RESULTS: In each of the subjects at every gait cycle, the patella was observed to move vertically first, followed by a sudden shift to the medial side before returning to its original position. CONCLUSION: Contrary to conventional understanding, our results show that the patella deviates medially rather than laterally during walking. This occurs because of differential contraction of the components of the quadriceps muscle during walking. The management of painful and subluxated patellae must be reevaluated in light of this finding. PMID- 8352121 TI - Cytologic analysis in fine-needle aspiration biopsy: smears vs cell blocks. AB - OBJECTIVE: Imaging-directed fine-needle aspiration biopsy can be performed with or without immediate cytologic assessment (smears). We compared the results obtained immediately from cytologic smears with the results of cell-block analysis. We wished to determine the frequency of false-negative findings on cytologic smears in patients subsequently found to have malignant tumors by cell block analysis. MATERIALS AND METHODS: We retrospectively reviewed the records for 100 consecutive biopsies performed between January 1986 and August 1987. In each case, specimens were obtained from both a 22-gauge and a 20-gauge notched needle placed in tandem. The study group consisted of 84 patients who had results of analyses of both cytologic smears and cell blocks available for review and who had clinical or surgical correlation. RESULTS: Sixty-four (76%) of the 84 biopsies yielded malignant tumor cells, 11 yielded evidence of a benign process, and nine were not diagnostic. Malignant tumor cells were seen on the cytologic smears in 55 (86%) of the 64 patients who had malignant tumors; in the other nine patients, the malignant tumors were indicated by the cell-block analysis only. Within the group of benign disorders, in only one case (9%) was the cell block diagnostic when the cytologic smear was not. CONCLUSION: Operators performing fine-needle aspiration biopsy should be aware of the limitations of immediate cytologic evaluation. Cell-block analysis of the aspirate remaining after the smears are made can be expected to increase the diagnostic accuracy in up to 14% of patients. PMID- 8352122 TI - CT-guided celiac ganglion block with alcohol. AB - Celiac ganglion block has been performed without radiologic guidance by surgeons or anesthetists since it was first described by Kappis [1] in 1914. Radiographic guidance for celiac block was first reported in the 1950s [2], and more recently, radiologists have used CT to guide needle placement [3-5]. With CT guidance, more directed positioning of the needle is possible, allowing alcohol to be deposited in the specific ganglion areas. This article reviews our collective experience with CT-guided celiac ganglion block. PMID- 8352123 TI - Dislodgment of inferior vena caval filters during "blind" insertion of central venous catheters. PMID- 8352124 TI - High-dose chloral hydrate sedation for children undergoing MR imaging: safety and efficacy in relation to age. AB - OBJECTIVE: Sedation is frequently essential for successful MR imaging, and chloral hydrate is the most commonly used drug for this purpose in infants and children. Our experience with these patients suggested that this sedative is less effective in older children, even when administered in high doses. However, no prospective study comparing the efficacy of chloral hydrate sedation for children of different ages undergoing MR imaging has been reported. Accordingly, we performed a study to evaluate the effectiveness and safety of chloral hydrate sedation in children of various ages. SUBJECTS AND METHODS: The study included 300 infants and children, 1 month to 11 years old (mean, 3 years), who were given oral chloral hydrate, 100 mg/kg, for sedation before MR imaging. The maximum total dose administered was 2.5 g, which limited the study to children who weighed 25 kg or less. Sedation was considered successful when MR studies were completed and at least 95% of the images had little or no motion artifact. RESULTS: Sedation was successful in 273 (91%) of 300 children. It was unsuccessful in nine of the 203 children who were 48 months old or younger (96% success rate) and in 18 of the 97 children who were more than 48 months old (81% success rate). A single-tailed t-test showed that the children in whom sedation was unsuccessful were significantly older than those in whom it was successful to the .0005 level of significance. The failure rate increased steadily for children more than 48 months old. Several failures may also have resulted from lengthy examination times. Adverse reactions to chloral hydrate sedation included hyperactivity (6%), vomiting (4%), and mild respiratory depression (4%). No adverse reaction was severe enough to require hospitalization. CONCLUSION: The higher failure rate for chloral hydrate sedation in children more than 48 months old suggests that the patient's age is an important limitation to the usefulness of chloral hydrate sedation for children undergoing MR imaging. However, the low rate of adverse reactions makes chloral hydrate a safe drug for sedation of children undergoing MR imaging. PMID- 8352125 TI - Osteomyelitis in hospitalized children with chickenpox: imaging findings in four cases. AB - OBJECTIVE: The most common complications of chickenpox are skin and soft-tissue infections. Pneumonia and CNS involvement occur less often, and skeletal complications are considered rare. The purpose of this study was to evaluate the imaging findings of osteomyelitis in children after chickenpox. MATERIALS AND METHODS: We retrospectively reviewed the records of children admitted to our institution because of chickenpox and analyzed the imaging findings in those who had skeletal involvement. Ninety-seven patients were admitted between January 1991 and January 1993 because of chickenpox or a complication thereof. Four previously healthy patients, three boys and one girl, between 1 and 6 years old had osteomyelitis. Staphylococcus aureus was isolated from bone in one patient, and group A beta-hemolytic streptococcus was isolated from blood cultures in another. No organism was grown in the other two; necrotic bone was recovered from one lesion and the other healed with periosteal formation of new bone typical of osteomyelitis. All patients were treated with IV antibiotics, and their recoveries were uncomplicated. RESULTS: Conventional radiographs showed loss of fat planes in three patients and destruction of bone in two. Bone scintigraphy showed increased uptake of radionuclide in early and late phases in three patients. Uptake in one case was extensive, with a central area of relatively little uptake corresponding to a subperiosteal fluid collection. CT in two and MR imaging in one showed subperiosteal fluid collections surrounding the involved bones in association with bone and marrow changes. CONCLUSION: Osteomyelitis was the fourth most common complication of chickenpox in our series. The appearances on conventional radiographs and scintigrams are indistinguishable from those of typical bacterial osteomyelitis. However, CT and MR imaging showed subperiosteal fluid collections in three of four patients, an appearance only occasionally seen with typical osteomyelitis. PMID- 8352126 TI - Aspergilloma complicating cystic fibrosis. PMID- 8352127 TI - Thoracic duct cyst in the middle part of the mediastinum. PMID- 8352128 TI - Retained surgical sponge after subtotal thyroidectomy. PMID- 8352129 TI - Extensive calcification in the inferior vena cava in an adult. PMID- 8352130 TI - Asymmetric uterine enlargement: a reliable sign of leiomyomas. PMID- 8352131 TI - Fibroepithelial polyp implanted on a ureterocele. PMID- 8352132 TI - Double gloving during interventional procedures. PMID- 8352133 TI - Bilateral acute thalamic infarcts causing thalamic dementia. PMID- 8352134 TI - Tuberous sclerosis with calcification of the cerebellar folia: CT and MR findings. PMID- 8352135 TI - Routine use of gadopentetate dimeglumine in cranial MR imaging of patients with AIDS. PMID- 8352136 TI - Tuberculosis of sphenoidal sinus: CT findings. PMID- 8352137 TI - Neuroendocrine tumor (paraganglioma) of the cauda equina: MR and pathologic findings. AB - The MR and pathologic features of a case with neuroendocrine tumor (paraganglioma) of the cauda equina are presented. MR showed the tumor to be hyperintense on postcontrast examination and also showed serpiginous flow voids suggesting vessels capping the tumor. A neuroendocrine tumor should be considered in the differential diagnosis of tumors in this location. PMID- 8352139 TI - Bilateral nasolacrimal duct mucocele, a rare cause of respiratory distress: CT findings in two newborns. AB - Two newborns presented with severe respiratory distress caused by nasal obstruction. CT showed bilateral soft-tissue masses located under the inferior turbinates at the level of the inferior meatuses. Histologic examination showed the lesions to be compatible with nasolacrimal mucoceles. The embryology and radiographic features of this rare anomaly are discussed. PMID- 8352138 TI - Infected congenital mucocele of the nasolacrimal duct. AB - The authors report their experience with an infant presenting with an infected nasolacrimal duct mucocele, emphasizing correlation of clinical, CT, and surgical findings. CT is the imaging modality of choice to demonstrate the triad of 1) a cystic medial canthal mass, 2) dilatation of the nasolacrimal duct, and 3) a submucosal nasal cavity mass; findings which are diagnostic of this entity. A brief review of the relevant embryology is also presented. PMID- 8352140 TI - High-dose cytarabine neurotoxicity: MR findings during the acute phase. AB - The authors report an acute cerebral and cerebellar syndrome in a patient treated with high-dose cytarabine. Diffuse high-intensity lesions in the central white matter on T2-weighted MR completely reversed with resolution of the clinical syndrome. Although the autopsy revealed cerebellar injury, the cerebral cortex was grossly and microscopically normal, consistent with a reversible process. PMID- 8352141 TI - Usefulness of brain blood-flow imaging. PMID- 8352142 TI - Oversight by authors? PMID- 8352143 TI - Specialization's absurd limit. PMID- 8352144 TI - Treatment of experimental canine carotid aneurysms with platinum coils. AB - PURPOSE: To evaluate and compare the deliverability, positioning, stability, and effectiveness of aneurysm occlusion and the incidence of parent-artery thrombosis of two different types of platinum coils, using a canine carotid aneurysm model. METHODS: 29 experimental canine carotid aneurysms (19 lateral, 6 bifurcation, and 4 terminal) were constructed and treated with complex-shaped fibered platinum coils and simple curved nonfibered platinum Guglielmi detachable coils (GDCs). RESULTS: Fibered complex coils were stable, producing 38% complete aneurysm occlusion and 61% average reduction in aneurysm lumen size but resulting in 19% parent artery occlusions. GDC coils were stable, producing 31% complete aneurysm occlusion and 95% average reduction in aneurysm lumen size with no parent-artery occlusions. CONCLUSIONS: GDC coils produced an average reduction in aneurysm lumen size of 95% without any associated parent-artery occlusions. There were no delayed migrations of GDC coils. The ability to remove, reposition, and detach a coil was the most significant feature of the GDC coil. PMID- 8352145 TI - Platinum coil coatings to increase thrombogenicity: a preliminary study in rabbits. AB - The authors investigate a modification of the Gugliemi detachable coil. They have developed a rabbit model and coating technique to test differences in thrombogenicity of platinum coils with a variety of polyurethanes. PMID- 8352146 TI - The "current" status of aneurysm treatment? PMID- 8352147 TI - Canine model of terminal arterial aneurysm. AB - A canine model of terminal aneurysms using a venous pouch surgical technique is described. This model mimics the anatomy and hemodynamics of some types of carotid and basilar tip aneurysms. This technique produces aneurysms 15 x 21 mm in size. The aneurysms have been used to investigate the hemodynamics and treatment of terminal aneurysms. PMID- 8352148 TI - An endovascular retrieving device for use in small vessels. AB - A new retrieval device for use in small vessels was evaluated in a canine model. Retrieval was attempted on 25 coils, three silicone balloons, and five catheter and guide wire fragments placed in the renal, pulmonary, hepatic, brachiocephalic, subclavian, carotid, and maxillary arteries. This was successful in 91% (30/33). The snare could also be selectively placed in the vertebral and proximal basilar arteries. PMID- 8352149 TI - Microcatheter retrieval device for intravascular foreign body removal. AB - A microcatheter foreign body retrieval device is described and its first two clinical applications are presented. The device functions identically to larger loop snare retrievers. It permits access to small vessels and was successful in its first clinical applications. PMID- 8352150 TI - Spinal epidural arteriovenous fistulas: arterial and venous approaches to embolization. AB - The authors describe two patients with multiple spinal arteriovenous fistulas and exclusive epidural venous drainage. Both presented with a myelopathy caused by compression by large epidural veins. Both had arterial embolizations, but one required a venous approach to achieve a stable clinical result. PMID- 8352151 TI - Carotid sinus syndrome and embolization procedures. AB - Two patients developed carotid sinus syndrome following embolization procedures. One patient had undergone balloon occlusion of the internal carotid artery; in the other patient, embolization of a carotid body tumor had been performed. The method of diagnosis as well as the etiology and treatment are discussed. PMID- 8352152 TI - Intraarterial papaverine for the treatment of vasospasm. AB - The authors describe the use of intraarterial papaverine to treat vasospasm following subarachnoid hemorrhage. Two cases are reported: a 40-year-old woman with a posterior communicating artery aneurysm and a 67-year-old man with a posterior cerebral artery aneurysm. Both patients developed symptomatic, angiographically demonstrated vasospasm that responded to papaverine infusion. PMID- 8352153 TI - MR imaging of Kallmann syndrome, a genetic disorder of neuronal migration affecting the olfactory and genital systems. AB - PURPOSE: We report the MR findings in nine patients with clinical and laboratory evidence of Kallmann syndrome (KS), a genetic disorder of olfactory and gonadal development. In patients with KS, cells that normally express luteinizing hormone releasing hormone fail to migrate from the medial olfactory placode along the terminalis nerves into the forebrain. In addition, failed neuronal migration from the lateral olfactory placode along the olfactory fila to the forebrain results in aplasia or hypoplasia of the olfactory bulbs and tracts. Patients with KS, therefore, suffer both reproductive and olfactory dysfunction. METHODS: Nine patients with KS underwent direct coronal MR of their olfactory regions in order to assess the olfactory sulci, bulbs, and tracts. A 10th patient had MR findings of KS, although the diagnosis is not yet confirmed by laboratory tests. RESULTS: Abnormalities of the olfactory system were identified in all patients. In particular, the anterior portions of the olfactory sulci were uniformly hypoplastic. The olfactory bulbs and tracts appeared hypoplastic or aplastic in all patients in whom the bulb/tract region was satisfactorily imaged. In two (possibly three) patients, prominent soft tissue in the region of the bulbs suggests radiographic evidence of neurons that have been arrested before migration. CONCLUSIONS: Previous investigators of patients with KS used axial MR images to demonstrate hypoplasia of the olfactory sulci but offered no assessment of the olfactory bulbs. In the present study we used coronal images to show hypoplasia of both olfactory sulci and bulbs. In addition, we found what we believe to be the radiologic correlate of arrested neuronal migration in KS. PMID- 8352154 TI - Kallmann syndrome: MR evaluation of olfactory system. AB - PURPOSE: To describe the MR appearance of the olfactory bulbs and tracts and temporal lobes in patients with Kallmann syndrome, a disorder characterized by hypogonadotropic hypogonadism and anosmia. METHODS: High-resolution MR scans with a surface coil placed over the nasion were performed in two patients with Kallmann syndrome. Coronal 3-mm thick contiguous sections were obtained through the olfactory bulbs and tracts. MR scans included volumetric analysis of the bulbs, tracts, temporal lobes, and hippocampi. RESULTS: No olfactory bulbs or tracts could be identified in patients with Kallmann syndrome. In comparison, the olfactory bulbs and tracts were identifiable in seven healthy volunteers. The temporal lobe and hippocampal volumes were comparable between control subjects and Kallmann patients. CONCLUSIONS: High-resolution surface-coil MR can identify the absence of olfactory bulbs and tracts in patients with Kallmann syndrome. Normal olfactory bulbs and tracts are easily discerned with surface-coil imaging. PMID- 8352155 TI - Kallmann syndrome: MR findings. AB - PURPOSE: To evaluate patients with known hypogonadotropic hypogonadism, some with known anosmia, for defective rhinocephalon development that resulted in olfactory tract abnormalities, an affliction known as Kallmann syndrome. METHODS: Six patients who clinically had hypogonadotropic hypogonadism were examined by MR. Thin coronal images of the interior frontal region were used to determine presence or absence of olfactory tract and to evaluate the olfactory sulci. RESULTS: Olfactory tracts were not seen in three of the six cases; two of which had hypoplastic olfactory sulci. CONCLUSIONS: T1-weighted MR examination of the inferior frontal region in the coronal plane can help determine whether a patient with hypogonadotropic hypogonadism, with or without clinically evident anosmia, is afflicted with Kallmann syndrome. PMID- 8352156 TI - Bringing Kallmann syndrome into focus. PMID- 8352157 TI - CT and MR in infants with pericerebral collections and macrocephaly: benign enlargement of the subarachnoid spaces versus subdural collections. AB - PURPOSE: To compare CT and MR in the differentiation of benign enlargement of the subarachnoid spaces and subdural collections in infants with macrocephaly. METHODS: MR was performed in 19 infants with macrocephaly, showing bifrontal enlargement of the subarachnoid spaces on CT. RESULTS: In 11 patients, a single fluid layer could be distinguished on MR of the pericerebral collections, suggesting benign enlargement of the subarachnoid spaces. In eight patients, two separate layers were clearly differentiated, an outer layer that was hyperintense on all sequences and an inner layer with the same intensity as the cerebrospinal fluid. This indicated the presence of subdural collections. These collections were mainly frontal in six and extended over the entire hemisphere in two patients. On CT, these separate lesions were seen only in three patients and missed in three others. In two final patients, CT findings were equivocal with evidence of membrane formation within the hypodense collections. In seven patients with a subdural collection, subdural-external drainage was performed. In three patients, the collection was hemorrhagic. The protein content of the fluid showed a mean of 1381.7 +/- 785.6 mg/dL. The MR and surgical findings of a subdural collection correlated with the absence of a family history of macrocrania, an age under 5 months, and acute clinical signs of vomiting, somnolence, and hypotonia. CONCLUSION: MR appears essential in the differential diagnosis between benign enlargement of the subarachnoid spaces and subdural collections in infants. PMID- 8352158 TI - PEHO syndrome (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy): neuroradiologic findings. AB - PURPOSE: To investigate the radiologic characteristics of the clinical progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) symptom complex. This complex is nonspecific, but within this syndrome, a subgroup with a defined neuropathologic phenotype and apparently autosomal recessive inheritance exists. METHODS: Brain CT or MR studies were performed on 21 patients with the clinical PEHO syndrome. Their previous neuroradiologic studies were re-evaluated. RESULTS: Twelve patients (group A) showed uniform changes with early progressive brain atrophy accentuated infratentorially, and abnormal myelination. The gyral pattern was normal. Brain atrophy of nine patients (group B) differed by being less progressive, supra- rather than infratentorial, and often combined with abnormal gyral formation. CONCLUSIONS: Postmortem studies permitted correlation of radiographic and morphologic findings in three cases. Two autopsied group A patients were compatible with the true PEHO syndrome, while one group B patient was incompatible. Group A seems to correspond to the core group of the PEHO syndrome. During a patient's life, a suggestive diagnosis of the true PEHO syndrome is thus feasible, although neuropathologic studies are needed for a conclusive diagnosis. PMID- 8352159 TI - An in vitro study of magnetization transfer and relaxation rates of hematoma. AB - PURPOSE: To assess, in an in vitro model of acute hematoma, whether hemoglobin immobilization by clot and red cell membrane aging can account for the T2 shortening usually attributed to deoxyhemoglobin. METHODS: Clotted and heparinized blood samples were packed (100% hematocrit). The apparent magnetization transfer rate (AMTR), T1 and T2 relaxation rates of the samples, and images with a volunteer's head were obtained at 1.5 T. RESULTS: The AMTR and T1 and T2 relaxation rates were unaffected by the presence of clot. The AMTR was unaffected by red cell aging. The diamagnetic packed blood samples, which are much denser than brain, were isointense to gray matter on T2-weighted images and had about one-fifth the AMTR of white matter. CONCLUSIONS: Hemoglobin immobilization by clot structure or red cell contraction with aging is insignificant and does not contribute to the T2 shortening of acute hematoma. The low AMTR and T2 relaxation rates of diamagnetic blood appear to be caused by the mobility of hemoglobin and by the red cell's lack of immobile macromolecular structures such as those associated with nucleated brain cells. PMID- 8352160 TI - Magnetization transfer effects in MR imaging of in vivo intracranial hemorrhage. AB - PURPOSE: Recent papers have hypothesized that diamagnetic effects of clotting and conformational changes in aging red blood cells immobilize the hemoglobin protein and thus are responsible for the marked hypointensity of acute hematomas on T2 weighted spin-echo MR images. To test that hypothesis, the authors evaluated 24 hemorrhagic components of intracranial hemorrhagic lesions using accepted criteria based on spin-echo images as the definitions of the stage of the hemorrhage. METHODS: As a measure of the effects of macromolecular (hemoglobin protein) immobility, magnetization transfer contrast was elicited using a pulsed saturation magnetization transfer experiment. The apparent magnetization transfer contrast (AMTC) was determined by comparing the signal intensities of saturated with unsaturated images and quantified for acute isolated hemorrhages, acute nonisolated hemorrhagic lesions, and subacute-to-chronic hemorrhages. RESULTS: The AMTC of isolated acute hemorrhage was significantly less than that of normal, white matter and gray matter, indicating the lack of significant magnetization transfer and therefore the lack of effects of restriction of hemoglobin mobility on the signal intensity of acute hemorrhage. Acutely hemorrhagic tissue (nonisolated acute hemorrhage) has significantly more AMTC than isolated acute hemorrhage, but still not exceeding that of brain parenchyma. CONCLUSION: This in vivo data concurs with in vitro data and reinforces the concept that the marked hypointensity of acute hematomas is mainly a magnetic susceptibility effect. PMID- 8352161 TI - CT in penetrating craniocervical injury by wooden foreign bodies: reminder of a pitfall. AB - The authors report three cases of penetrating craniocervical injury by wooden foreign bodies, which were initially hypodense on CT and thought to be air. When these structures were scrutinized with higher window settings, they had a higher attenuation and a unique striated internal architecture which the authors propose may be specific to wood. PMID- 8352163 TI - Interuncal distance measurements in healthy volunteers and in patients with Alzheimer disease. AB - PURPOSE: To evaluate further the clinical utility of the interuncal distance (IUD) measured from axial MR scans as a reflection of hippocampal atrophy. METHODS: The IUD measured from the axial MR scans of 17 healthy control subjects was correlated with the volume of the amygdala hippocampal complex obtained from coronal MR images. The IUD was also measured on axial MR scans in 12 patients with possible or probable Alzheimer disease. RESULTS: The correlation between the total amygdala hippocampal volume and the IUD was insignificant for control subjects (r = -0.38, P = .13). When analysis of covariance was performed with the IUD as the dependent variable and age and diagnosis as the independent variables, overall R2 was 0.25. Age (F = 5.02, df = 1, P = .034), but not diagnosis (F = 0.02, df = 2, P = .88), had a significant effect. CONCLUSIONS: The IUD has no significant correlation with the amygdala hippocampal volume. The IUD appears to be a better measure of overall brain volume, which changes with age. In our patient population diagnosed with mild to moderate Alzheimer disease, the IUD measurement was not found to be useful in distinguishing their scans from those of the volunteers. PMID- 8352162 TI - The radiologic prediction of Alzheimer disease: the atrophic hippocampal formation. AB - PURPOSE: To test the hypothesis that atrophy of the hippocampal formation in nondemented elderly individuals would predict subsequent Alzheimer disease. METHOD: We studied 86 subjects at two time points, 4 years apart. At baseline all study subjects were nondemented and included 54 control subjects and 32 persons who had memory complaints and minimal cognitive impairments. All subjects received a CT scan using a protocol designed to image the perihippocampal cerebrospinal fluid (HCSF) accumulating in the fissures along the axis of the hippocampal formation. Blind to the clinical evaluations, we subjectively assessed the presence of HCSF at the baseline. Retrospectively, we examined the predicted association between baseline HCSF and clinical decline as determined across the two evaluations. RESULTS: At follow-up 25 of the 86 subjects had deteriorated and received the diagnosis of Alzheimer disease. Of the declining subjects, 23 came from the minimally impaired group, and 2 came from the control group. In the minimally impaired group the baseline HCSF measure had a sensitivity of 91% and a specificity of 89% as a predictor of decline. Both control subjects who deteriorated were also correctly identified at baseline. One of these two subjects died, and an autopsy confirmed the presence of Alzheimer disease. M(r) validation studies demonstrated that HCSF is quantitatively related to dilatation of the transverse fissure of Bichat and the choroidal and hippocampal fissures. CONCLUSION: Our findings strongly suggest that among persons with mild memory impairments, dilatation of the perihippocampal fissures is a useful radiologic marker for identifying the early features of Alzheimer disease. PMID- 8352164 TI - Reflections from the backseat. PMID- 8352165 TI - Locating the central sulcus: comparison of MR anatomic and magnetoencephalographic functional methods. AB - PURPOSE: To compare MR anatomic and magnetoencephalographic (MEG) functional methods in locating the central sulcus. METHODS: Eleven healthy subjects and five patients with focal cerebral lesions were studied. The central sulcus was located anatomically with MR by two independent observers using axial vertex and sagittal (midline and lateral) images. Locations via the MEG functional method were based on detecting the somatosensory-evoked magnetic fields elicited by painless tactile stimuli. RESULTS: The axial method yielded the most consistent interrater results, with complete agreement in 76% of sections in both control subjects and patients. The intermethod discordance of the sagittal midline and lateral methods was 32% in control subjects and 33% in patients. The concordance of MR and MEG methods ranged from 55% to 84% in control subjects and 65% to 67% in patients. CONCLUSION: MR anatomic techniques can usually identify the central sulcus, but in the presence of anatomic distortion, the MEG functional method adds significant information. PMID- 8352166 TI - The central sulcus and surgical planning. PMID- 8352167 TI - Radiologic-pathologic correlation. Diffuse pontine astrocytoma. AB - This case demonstrated the classic gross, pathologic, CT, and MR findings of pontine astrocytoma. The role of functional brain imaging in identifying regrowth of tumor was illustrated and the differential diagnosis of a brain stem lesion summarized. PMID- 8352168 TI - Predominantly extraaxial astroblastoma: imaging and proton MR spectroscopy features. AB - The CT, angiographic, MR, and proton MR spectroscopy findings in a case of astroblastoma, a rare neoplasm of glial cell origin, are presented. Of particular interest is the predominantly extraaxial location of the tumor. CT and MR demonstrated a complex mass consisting of a solid nodule and a peripheral septated cystic component. The extraaxial nature of the mass was suggested on MR. PMID- 8352169 TI - Neuroepithelial (colloid) cyst of the cerebellar vermis containing a xanthogranuloma. AB - A case of a neuroepithelial cyst of the cerebellar vermis is presented. The cyst contained a viscous fluid and a xanthogranulomatous nodule. The fluid showed high signal on T1- and low signal on T2-weighted MR images. The xanthogranuloma showed mixed intensities with partial contrast enhancement. The correlation of the cyst contents and MR signals is discussed. PMID- 8352170 TI - Multicenter trial of gadoteridol, a nonionic gadolinium chelate, in patients with suspected head and neck pathology. AB - PURPOSE: To evaluate the safety and efficacy of gadoteridol as an MR contrast agent in patients with suspected head and neck pathology. METHODS: One hundred thirty-three adult patients were studied with MR at 12 clinical trial sites before and after the intravenous administration of 0.10 mmol/kg gadoteridol. After enrollment, patients underwent a complete physical examination. Patient monitoring included vital signs, laboratory tests, and recording of the incidence and duration of adverse events. To evaluate efficacy, postcontrast T1-weighted images were compared with precontrast T1- and T2-weighted images. Investigators having clinical information evaluated 129 studies for efficacy; two readers blinded to clinical information subsequently evaluated 122 studies using the same criteria as the investigators. RESULTS: Eight patients (6.0%) experienced mild adverse events possibly or probably related to contrast administration, all of which resolved without treatment. Two clinically significant laboratory abnormalities considered related or possibly related to the administration of gadoteridol were reported in two patients. Enhancement of pathology was seen in 82.9% of cases evaluated by investigators at the study site and in 78.7% of cases subsequently evaluated by the blinded readers. Postcontrast images were judged by investigators to provide additional diagnostic information over precontrast images in 68.9% of studies. The additional diagnostic information available on postcontrast studies most often consisted of improved visualization of pathology and better definition of lesion borders. The use of this information might have contributed to a change in patient diagnosis in 18.6% of the cases evaluated by the investigators and in 16.4% of the cases reviewed by the blinded readers. CONCLUSIONS: Preliminary results show gadoteridol to be a safe and efficacious contrast agent for enhanced MR study of extracranial and extraspinal head and neck pathology. PMID- 8352171 TI - Irreversible regional cerebral ischemia: serial MR imaging and proton MR spectroscopy in a nonhuman primate model. AB - PURPOSE: To delineate the changes in proton MR spectroscopy and imaging that occur with acute, irreversible ischemia of the basal ganglia of a baboon. MATERIALS AND METHODS: The M1 segments of the middle cerebral arteries of six adult male baboons were occluded by endovascular means with microcatheters and N butyl cyanoacrylate adhesive. Cerebral blood flow measurements were taken with positron emission tomography or radioactive microsphere techniques. Serial spatially localized proton MR spectroscopy of the basal ganglia and MR imaging of the brain were performed. The distribution of ischemic and infarcted tissue was demonstrated by histopathologic techniques or triphenyltetrazolium chloride staining. RESULTS: Radioactive microsphere or positron emission tomography measurements demonstrated no significant cerebral blood flow within the basal ganglia after occlusion of the middle cerebral artery. Proton MR spectroscopy of the basal ganglia demonstrated increasing cerebral lactate and decreasing N acetyl aspartate within 30 minutes of middle cerebral artery occlusion. Changes in the MR imaging signal intensity of the basal ganglia were observed as early as 3.1 hours on T2-weighted, 3.3 hours on T1-weighted, and 6.1 hours on spin density weighted images. The distribution of these changes correlated well with the histopathologic features of ischemia and infarction that were seen throughout the basal ganglia. CONCLUSION: Changes in MR imaging signal intensity corresponded to ischemia and infarction in our baboon model of acute irreversible ischemia of the basal ganglia. Increasing cerebral lactate and decreasing N-acetyl aspartate preceded changes in MR imaging signal intensity. PMID- 8352173 TI - Aneurysms and MR angiography. PMID- 8352172 TI - MR angiographic demonstration of an intracranial aneurysm not seen on conventional angiography. AB - A patient with documented subarachnoid hemorrhage underwent conventional angiography, which was negative. MR angiography performed immediately after the conventional angiogram demonstrated a 4-mm anterior communicating artery aneurysm. This finding was confirmed 1 week later with repeat angiography, and the aneurysm was clipped surgically. PMID- 8352174 TI - Anatomy of the jaw revisited with a dental CT software program. AB - The jaw has traditionally been evaluated by dentists and oral surgeons using conventional panoramic and intraoral films. Recently, CT software programs specifically developed to evaluate dental implant patients have provided radiologists with a new look at the mandible and maxilla. The anatomy seen on these reformatted panoramic and cross-sectional images is complex, and our objective is to define it. By the use of standard anatomic drawings, mandibular and maxillary anatomy was identified on human skulls and then on the axial, cross sectional, and panoramic DentaScan images of these skulls. With this anatomic description, the DentaScans from several representative patients were then used to portray mandibular and maxillary anatomy in a pictorial fashion. PMID- 8352176 TI - MR contrast enhancement: an experimental study in postlaminectomy epidural fibrosis. AB - PURPOSE: To measure the effect of contrast medium dose, time elapsed since injection, and maturity of epidural scar tissue on the enhancement of scar tissue in MR imaging. METHODS: We imaged 12 beagle dogs with MR at 10 to 60 days after lumbar laminectomy, and at necropsy we obtained exactly correlating histologic sections. Contrast enhancement of scar tissue at 2, 15, 40, and 60 minutes after 0.1 and 0.3 mmol of paramagnetic contrast medium per kilogram was measured. Contrast enhancement was analyzed with respect to the dose of contrast medium, the time of imaging, and the maturity of scar tissue. RESULTS: Epidural scar tissue enhanced more intensely at 2 and at 15 minutes than at 40 or at 60 minutes. Consistently greater enhancement was observed with the dose of 0.3 mmol/kg than with the dose of 0.1 mmol/kg. Regions of loosely organized scar tissue enhanced less intensely and less quickly than did more organized scar tissue. CONCLUSION: Contrast enhancement in scar tissue can be heightened by increasing the dose of contrast medium from 0.1 to 0.3 mmol/kg and by obtaining images within 15 minutes of injection. PMID- 8352175 TI - Segmental enhancement of the cochlea on contrast-enhanced MR: correlation with the frequency of hearing loss and possible sign of perilymphatic fistula and autoimmune labyrinthitis. AB - PURPOSE: To relate the finding of selective enhancement of different turns of the cochlea to the frequency range of the hearing loss measured by audiogram. METHODS: Six patients aged 23 to 53 years, four men and two women, who presented with sudden hearing loss and had segmental enhancement of different turns of the cochlea on contrast-enhanced MR imaging were included in this retrospective study. The patients were imaged on a 1.5 T MR imaging system using pre- and postcontrast axial T1-weighted images and postcontrast coronal T1-weighted images through the temporal bone. RESULTS: The basal turn of the cochlea enhanced selectively in five of the six patients and the apical turn enhanced in the sixth patient. All patients had sensorineural hearing loss. Three of the patients with basal turn enhancement had predominantly high-frequency hearing loss, whereas the patient with apical turn enhancement had predominantly low-frequency hearing loss. The two other patients with basal turn enhancement had complete hearing loss. Three patients had presumed autoimmune labyrinthitis. The other three patients had strong clinical and surgical evidence of a perilymphatic fistula. CONCLUSION: Contrast-enhanced MR imaging may demonstrate selective enhancement of different turns of the cochlea. In certain patients, the areas of enhancement may correlate with specific hearing loss in the frequencies mapped by the enhancing segment. Enhancement of the cochlea may represent radiologic evidence of cochlear inflammation secondary to a perilymphatic fistula. PMID- 8352177 TI - Effect of cigarette smoking on coronary patency after thrombolytic therapy for myocardial infarction. TEAM-2 Investigators. Second Multicenter Thrombolytic Trials of Eminase in Acute Myocardial Infarction. AB - Smokers have been reported to have an improved short-term prognosis after myocardial infarction when compared with nonsmokers. This study examines the effect of smoking status on infarct-related artery patency, a determinant of outcome, following thrombolytic therapy for acute myocardial infarction (AMI). To evaluate patency outcome by smoking status, the database of the Second Thrombolytic Trial of Eminase in Acute Myocardial Infarction was reviewed, and baseline characteristics were compared with infarct-related artery patency early (90 to 240 minutes) after thrombolysis in smokers versus nonsmokers. Smokers were younger (mean age 53 vs 59 years, p = 0.0001), more likely to be men (86 vs 73%, p = 0.008), normotensive (74 vs 58%, p = 0.004), to have an inferior infarction (66 vs 51%, p = 0.007), and tended to have higher hematocrits and fibrinogen levels than nonsmokers. Smokers had a significantly greater chance of achieving complete perfusion (Thrombolysis in Myocardial Infarction trial grade 3) (66 vs 51% p = 0.007) than nonsmokers, although the combination of grades 2 and 3 did not differ. After correcting for imbalances in baseline and angiographic variables, multivariate logistic regression identified smoking (odds ratio 1.8, p = 0.01) and infarct location (odds ratio 1.7, p = 0.03) as independent predictors of achieving grade 3 flow. The independent predictive component of smoking for achieving grade 3 patency after thrombolysis suggests the hypothesis that more active thrombogenic mechanisms may be operative in smokers, leading to a larger thrombus component that is more susceptible to lytic therapy. PMID- 8352178 TI - Impact of tissue plasminogen activator and heparin versus heparin alone on quantitative coronary angiographic findings in myocardial infarction. The Toronto Tissue Plasminogen Activator Trial Study Group. AB - The influence of tissue plasminogen activator (t-PA) and heparin versus heparin alone on anatomic characteristics of patent infarct-related coronary arteries and the development of these angiographic descriptors in coronary arteries that remain patent during the hospital course was examined in 108 patients who participated in a placebo-controlled trial of recombinant tissue-type plasminogen activator in acute myocardial infarction. Coronary angiography was performed 18 +/- 6 hours after treatment in 47 patients (group A) and at 10 days in 61 patients (group B). Quantitative coronary angiography of the infarct-related lesion was performed, and luminal irregularity was quantitated with an ulceration index. Of the 47 patients in group A, 7 (29%) treated with placebo had Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, whereas 18 (78%) treated with t-PA had grade 2 or 3 (p < 0.001); there was no difference between patients who had grade 2 or 3 perfusion in group B (placebo 59% vs t-PA 75%). In group A, at 10 days, the luminal area of the infarct artery had increased from 0.59 +/- 0.11 to 0.9 +/- 0.24 mm2 and from 0.75 +/- 0.16 to 1.31 +/- 0.39 mm2 for placebo- and t-PA-treated patients, respectively (p < 0.04). There was no change in the ulcerative index over time in either placebo- or t-PA-treated patients. It is concluded that early after infarction, t-PA produces marked and rapid improvement in overall patency as compared with heparin, although this difference was attenuated at 10 days because of spontaneous recanalization in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352179 TI - Influence of transdermal scopolamine on cardiac sympathovagal interaction after acute myocardial infarction. AB - In 41 survivors of acute myocardial infarction (AMI) a prospective study was performed in 2 sequential phases. In phase 1, the role of baroreflex sensitivity and heart rate variability as predictors of inducible and spontaneous sustained ventricular tachyarrhythmias was evaluated. In phase 2, the effects of transdermal scopolamine on baroreflex sensitivity, spectral and nonspectral measures of heart rate variability were investigated. At a mean follow-up of 10 +/- 3 months after AMI, 5 of 41 patients (12%) developed a late arrhythmic event. Of these, all (100%) had inducibility of sustained monomorphic ventricular tachycardia at programmed stimulation compared with 3 of 36 patients (8%) without events (p < 0.0001). At multivariate analysis, baroreflex sensitivity had the strongest relation to both inducibility of sustained monomorphic ventricular tachycardia (p < 0.0001) and occurrence of arrhythmic events (p < 0.0001). Of 41 patients, 28 (68%) consented to undergo phase 2 of the investigation. Baroreflex sensitivity significantly (p < 0.00001) increased after transdermal scopolamine as well as heart rate variability indexes. Of these, the mean of SDs of normal RR intervals for 5-minute segments (p < 0.0001) and the total power (p < 0.0001) had the most significant improvement after scopolamine. The present investigation confirms that assessment of autonomic function is an essential part of arrhythmic risk evaluation after AMI. Transdermal scopolamine, administered to survivors of a recent AMI, reverses the autonomic indexes that independently predict arrhythmic event occurrence. On the basis of these data, transdermal scopolamine could be a potential useful tool in the prophylaxis of life-threatening ventricular arrhythmias after AMI. PMID- 8352180 TI - Effect of intravenous nitroglycerin on heparin dosage requirements in coronary artery disease. AB - Patients admitted to the coronary care unit who received both intravenous nitroglycerin and heparin were studied to evaluate heparin dosage requirements. Physicians ordered all nitroglycerin and heparin doses as well as coagulation studies without knowledge of this study. Activated partial thromboplastin time (APTT) values obtained during steady-state heparin administration were considered therapeutic if the ratio of APTT/APTT-baseline was > or = 1.5. Sixty patients with myocardial infarction or unstable angina were included in the study. The initial therapeutic heparin dose of 1,014 +/- 151 units/hour produced an APTT ratio of 2.0 +/- 0.5. At the time of the initial therapeutic dose, the nitroglycerin dose was 110 +/- 108 micrograms/min. There was a significant correlation between the initial therapeutic dose and both total (r = 0.56; p = 0.0001) and lean (r = 0.26; p < 0.05) body weight. Comparison of patients with nitroglycerin doses < and > or = 100 micrograms/min revealed a significant difference in the initial therapeutic dose (971 +/- 147 vs 1,077 +/- 136 U/hour, p < 0.01), but not the initial therapeutic dose standardized to total body weight (14.0 +/- 2.5 vs 13.5 +/- 2.7 U/kg/hour). Similarly, analysis of variance revealed a significant difference in the initial therapeutic dose (p < 0.05), but not the initial therapeutic dose standardized to weight among 5 different nitroglycerin dosage ranges (10 to 533 micrograms/min). Neither aspirin use, thrombolytic therapy nor decreasing or discontinuing the nitroglycerin dose significantly affected heparin requirements. Thus, contrary to prior reports, clinically significant heparin resistance induced by nitroglycerin was not found. PMID- 8352181 TI - Interrelation between angiographic severity of coronary artery disease and plasma levels of insulin, C-peptide and plasminogen activator inhibitor-1. AB - Plasma insulin, C-peptide and plasminogen activator inhibitor-1 (PAI-1) levels were measured in 64 men with coronary artery disease (CAD) documented by angiography. Coronary arteriograms were analyzed, and the severity and diffusion of coronary lesions were quantified by score systems. C-peptide and PAI-1 levels in patients with CAD were significantly higher than in 30 control subjects. Insulin, C-peptide and PAI-1 showed a highly significant correlation with the severity scores for coronary lesions (C-peptide more than insulin), but only a weak correlation with diffusion scores. Highly significant correlations were found between insulin and PAI-1, and even greater ones between C-peptide and PAI 1. It has been proposed that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease by dysregulating lipoprotein metabolism and blood pressure. These findings support that hypothesis and suggest that insulin secretion may be an index of the severity of CAD. Because a direct effect of insulin on the cells that synthesize PAI-1 has been shown, the present data further indicate that the effect of insulin on fibrinolysis may be another way by which hyperinsulinemia accelerates atherogenesis. PMID- 8352182 TI - Elevated plasma lipoprotein(a) associated with abnormal stress thallium scans in children with familial hypercholesterolemia. AB - Plasma lipoprotein(a) (Lp(a)) concentrations are associated with an increased risk of coronary artery disease in adults with familial hypercholesterolemia (FH). We hypothesized that Lp(a) concentrations in children with FH were higher among those with myocardial ischemia on stress thallium scans and among those with a family history of premature coronary artery disease. Twenty-nine asymptomatic heterozygotes with FH (range 9 to 23 years) and 7 homozygotes (range 4 to 13 years) were evaluated with clinical assessment, lipoprotein measurement and stress thallium scans. Compared with subjects with normal stress thallium scans, mean Lp(a) was significantly higher in homozygotes with stress thallium abnormalities (79 +/- 18 vs 15 +/- 5.5 mg/dl, p = 0.03), and tended to be higher in heterozygotes with stress thallium abnormalities (39 +/- 12 vs 20 +/- 4.2 mg/dl, p = 0.10). Lp(a) tended to be higher in heterozygotes with a family history of premature coronary artery disease (30 +/- 6.4 vs 14 +/- 4.1 mg/dl, p = 0.12). It is concluded that Lp(a) is higher in hypercholesterolemic children who have abnormal stress thallium scans. Lp(a) may be useful in assessing coronary artery disease risk in children with FH. PMID- 8352183 TI - Cardiac adaptation to increased systemic blood pressure in borderline hypertensive men. AB - The present study examined cardiac characteristics of borderline hypertensive men with a positive parental history of hypertension. Hemodynamics in relation to left ventricular function and structure were evaluated in 15 borderline hypertensive men with a parental history of hypertension and in 20 normotensive control subjects with a negative parental history. Groups were matched in age, height, weight and percent body fat. Left ventricular mass and dimensions were measured by M-mode echocardiography, and left ventricular function was assessed by radionuclide ventriculography. Both groups had similar left ventricular mass, dimensions and wall thicknesses. In relation to control subjects, borderline hypertensive men had a significantly higher heart rate and blood pressure (BP) (p < 0.001), but a similar cardiac index. Borderline hypertensive men had a higher peripheral resistance index (p < 0.02), longer time to peak filling rate, and reduced cardiac efficiency, whereas they had higher contractility, minute and stroke work indexes than did control subjects (all p < 0.05); they also had higher diastolic BP (p < 0.03) during exercise, and sustained higher BP during recovery than did controls. Although this group of borderline hypertensive men did not have an altered cardiac anatomy, they had an increased vascular resistance, an altered diastolic function and a reduced cardiac efficiency while undergoing a greater work load. These cardiodynamic profiles are consistent with functional vascular changes and a parallel compensation by the heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352184 TI - Clinical and hemodynamic predictors of survival in patients aged < 65 years with severe congestive heart failure secondary to ischemic or nonischemic dilated cardiomyopathy. AB - To identify which clinical or hemodynamic parameters predict survival in patients with end-stage heart failure due to dilated cardiomyopathy, 130 consecutive patients aged < 65 years (mean 46 +/- 13) assessed for heart transplantation from May 1986 to April 1991 were studied. Mean follow-up was 15 +/- 11 months. Left ventricular ejection fraction was 22 +/- 7%. Left ventricular end-diastolic pressure was 27 +/- 9 mm Hg, and cardiac index was 2.2 +/- 0.6 liter/min/m2. Symptom class was IV in 91% of patients and III in 9%. Etiology was ischemic in 40% of patients and idiopathic in 60%. After intensive medical therapy, heart transplantation was considered indicated in 53% of patients, contraindicated in 20% and not indicated in 27%. Transplantation was performed in 36% of patients during follow-up, and 35% died and 29% were alive without transplantation. A comparison, excluding patients with transplantation, was performed between those who were alive and had survived > or = 6 months after assessment, and those who died. On multivariate analysis, the following 3 parameters were independent predictors of prognosis: intravenous inotropic requirement (p < 0.001), maximal, tolerated captopril dose (p = 0.013) and systolic blood pressure (p = 0.003). When patients with transplantation were considered as deaths, stabilization on medical therapy also reached statistical significance (p = 0.009). Classic prognostic markers including ventricular arrhythmias, left ventricular end diastolic pressure, cardiac index, amiodarone therapy and etiology were not associated with prognosis in this homogeneous population of severely ill patients. PMID- 8352185 TI - Effects of orthostatic stress on peripheral capillary filtration in mild congestive heart failure after healing of myocardial infarction. AB - Patients with heart failure have impaired baroreflex control of the peripheral circulation with attenuated vasoconstrictor response during orthostatic stress. The aim of this study was to test if this impaired baroreflex control not only affects the arterial, but also the capillary bed. Blood flow and capillary filtration were measured in the forearm (plethysmography) in 7 normal subjects and 7 patients with mild congestive heart failure (New York Heart Association functional class II). Measurements were done with the subjects supine and during head-up tilt at 45 degrees. While supine, forearm vascular resistance and capillary filtration coefficient did not differ significantly between the groups. In the control subjects, tilt decreased capillary filtration coefficient by 14 +/ 3% (p < 0.02), and increased forearm vascular resistance by 88 +/- 37% (p < 0.02); in contrast, patients with heart failure had an increase in capillary filtration coefficient of 26 +/- 5% (p < 0.02) and only increased the forearm vascular resistance by 10 +/- 1%, (p = NS, p = 0.26). Our data provide evidence that patients with mild heart failure, in contrast to normal subjects, increase the peripheral capillary filtration during orthostatic stress. The data indicate that impaired baroreflex mechanisms might influence the capillary filtration and it is suggested that impaired baroreflex control of the peripheral circulation can contribute to formation of edema in patients with heart failure. PMID- 8352186 TI - Effectiveness of amiodarone and electrical cardioversion for chronic rheumatic atrial fibrillation after mitral valve surgery. AB - Thirty consecutive patients with chronic rheumatic atrial fibrillation (AF) > or = 3 months after successful mitral valve surgery and left atrial diameter < or = 60 mm were treated with oral amiodarone. Protocol included high loading dosages of amiodarone for 4 weeks, and if conversion to sinus rhythm (SR) was not achieved then electrical cardioversion was performed. Patients converted to SR were maintained on low-dose amiodarone for another 4 weeks when treatment was discontinued. Overall, 23 patients (77%) converted to SR after 4 weeks of therapy: 12 (40%) taking amiodarone alone and 11 (37%) with the addition of electrical cardioversion. The duration of AF > 48 months was an adverse factor in the ability to restore SR. Sixteen patients (70%) remained in SR at a mean follow up of 17 months. The duration of AF < or = 48 months alone or in combination with left atrial diameter < or = 45 mm were the best predictors for long-term maintenance of SR. Thus, short-term amiodarone with or without electrical cardioversion is effective and safe in the treatment of chronic rheumatic AF after mitral valve surgery. The duration of AF and left atrial size can be used to identify patients with successful outcome. PMID- 8352187 TI - Clinicopathologic features of hypertrophic cardiomyopathy managed by cardiac transplantation. AB - Clinical records, electrocardiographic, echocardiographic, hemodynamic and radionuclide data, and the operatively excised hearts were reviewed in 10 patients (aged 19 to 46 years, mean 35) who had cardiac transplantation for hypertrophic cardiomyopathy. Severe congestive heart failure unassociated with outflow obstruction was the indication for transplantation in 9 patients. During a pretransplantation period ranging from 45 to 312 months (mean 137) in these 9 patients, pulmonary artery wedge pressure increased from 19 +/- 9 to 27 +/- 7 mm Hg, left ventricular ejection fraction decreased from 51 +/- 11% to 41 +/- 1%, left ventricular end-diastolic dimension increased from 42 +/- 6 to 48 +/- 4 mm, and total 12-lead QRS voltage decreased from 209 +/- 50 to 156 +/- 41 mm. In these 9 patients, the explanted hearts had dilated left ventricular cavities, and 8 had left ventricular scars without significant narrowing of the epicardial coronary arteries. The tenth patient had a nondilated left ventricular cavity and had transplantation because of recurrent, refractory syncope. Of the 10 patients, 3 died within the first month, and another died 8 months after transplantation. The remaining 6 patients have survived 20 to 54 months (mean 39) after transplantation and are in functional class I or II. PMID- 8352188 TI - A new hemostatic puncture closure device for the immediate sealing of arterial puncture sites. AB - After angiography, 6 to 24 hours of bedrest is indicated to assure that adequate hemostasis of the femoral artery has been achieved. Recently, a new hemostatic puncture closure device (HPCD) has been developed, which consists of a resorbable polymer anchor, a resorbable suture, a small collagen plug and an 8Fr delivery device. The device is delivered into the femoral artery through the introducer sheath, the anchor is secured against the intraluminal artery wall, and the collagen plug is deployed on the arterial wall. The prototype of the HPCD was used in 20 patients administered heparin. After insertion of the HPCD, hemostasis was achieved in 1.2 +/- 2.1 minutes; in 2 patients a light pressure dressing was applied for 4 hours to stop oozing. No late bleeding occurred. In 1 patient the positioning suture broke, requiring the application of a pressure bandage. Patients were uneventfully mobilized after 6.7 +/- 3.5 hours. In all patients serial duplex scanning of the femoral artery was performed before and after 1, 7, 30 and 90 days after HPCD placement. In 5 patients a small subcutaneous hematoma close to the site of introduction could be detected by ultrasound 1 day after catheterization. All but 1 patient had normalization of the flow patterns in the femoral artery. It is concluded that: (1) the HPCD is an effective device to achieve immediate hemostasis after arterial catheterization despite antithrombotic therapy, (2) early mobilization was uneventful, (3) duplex ultrasound studies demonstrated only transient changes in the punctured femoral artery, and (4) further investigations are needed to establish the efficacy and safety of the device. PMID- 8352189 TI - Evaluation of treatment strategies of malignant ventricular tachyarrhythmias in the era of the implantable defibrillator. PMID- 8352190 TI - Insulin resistance, glucose intolerance, hyperinsulinemia and dyslipidemia in patients with angiographically demonstrated coronary artery disease. PMID- 8352191 TI - Angiographic eligibility of community hospital patients with multivessel coronary artery disease for percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. PMID- 8352192 TI - Anti-streptokinase antibodies inhibit fibrinolytic effects of anistreplase in acute myocardial infarction. PMID- 8352193 TI - Acute myocardial gray level intensity changes detected by transesophageal echocardiography during intraoperative ischemia. PMID- 8352194 TI - Reproducibility of a positive passive upright tilt test at a seven-day interval in patients with syncope. PMID- 8352196 TI - Responses to dynamic cardiomyoplasty for idiopathic dilated cardiomyopathy. The McGill Cardiomyoplasty Group. PMID- 8352195 TI - A characteristic electrocardiographic pattern indicative of manifest left-sided posterior septal/paraseptal accessory atrioventricular connections. PMID- 8352197 TI - Effects of captopril on renal function before and after surgical correction of aortic coarctation. PMID- 8352198 TI - Transesophageal echocardiography in congenital submitral aneurysm. PMID- 8352199 TI - Absence of adenosine-induced chest pain after total cardiac afferent denervation. PMID- 8352201 TI - Systemic but not renal production of prostacyclin is highly reduced in cyclosporin-treated heart transplant recipients. PMID- 8352200 TI - Effects of acute administration of cyclosporine on levels of cardiovascular hormones in heart transplant recipients. PMID- 8352202 TI - Survey of selected cardiologists for an operational definition of normal sinus heart rate. PMID- 8352203 TI - Accuracy of a new nongeometric pulsed Doppler method in cardiac output evaluation. PMID- 8352204 TI - Proper probe size for pediatric transesophageal echocardiography. PMID- 8352205 TI - Blood cyst of the pulmonary valve causing pulmonic valve stenosis. PMID- 8352206 TI - Effects of coronary stenosis severity on variability of quantitative angiography. PMID- 8352207 TI - In rates we trust. PMID- 8352208 TI - US immunization system Rx: install new components. PMID- 8352209 TI - Benign neonatal sleep myoclonus. PMID- 8352210 TI - On Tiny Tim, Charles Dickens, and pediatrics. PMID- 8352211 TI - Bah humbug. PMID- 8352212 TI - What was wrong with Tiny Tim? PMID- 8352213 TI - Tiny Tim, Dickens, renal disease, and rickets. PMID- 8352214 TI - Food-induced bleeding from lymphonodular hyperplasia of the colon. PMID- 8352215 TI - Lateral medullary syndrome following varicella infection. PMID- 8352216 TI - Injuries to preschool-age children in day-care centers. A retrospective record review. AB - OBJECTIVES: To increase our understanding of the epidemiologic nature of injuries to children in day-care settings by examining injury logs and to determine appropriate methods for calculating injury rates. DESIGN: Retrospective, with data collected through a review of 1 year's records. SETTING: Four suburban day care centers in the upper Midwest. PARTICIPANTS: Five hundred twenty-seven preschool-age children, 275 of whom experienced one or more injuries during the study period. SELECTION PROCEDURE: Convenience sample. MEASUREMENTS/RESULTS: Injury rates were calculated based on the number of hours spent in day care in the study year. More than 1000 injuries were reported for 527 children. Injury rates ranged from 0.006 to 0.049 per child per standardized 8-hour day in a day care center (or six to 49 injuries per 1000 children per 8 hours of exposure). However, most injuries were minor, and none resulted in a fatality or hospital admission. Using this method, injury rates were examined by gender and month. CONCLUSIONS: Future research should determine exposure time based on the actual number of hours a child spends in attendance to determine injury rates. Exposure time should also be carefully considered in determining product- and location specific rates of injury. PMID- 8352217 TI - Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccine in infants. AB - OBJECTIVE: To compare the safety and immunogenicity of three investigational lots of Haemophilus influenzae type b polysaccharide-tetanus toxoid (PRP-T) conjugate vaccine in infants. DESIGN: A multicenter, randomized immunogenicity trial. Infants were vaccinated at 2, 4, and 6 months of age with one of three lots of PRP-T. A control group received H influenzae type b oligomers conjugated to CRM197 (HbOC). Serum was obtained before each injection and 1 month after the third dose, and assayed blindly for antibody in one laboratory. SUBJECTS: Four hundred eighty-four infants from private pediatric practices located in five geographic areas. MEASUREMENTS AND RESULTS: There were no significant differences in the number of adverse events reported for infants receiving PRP-T or HbOC, and the rates did not exceed those observed previously in infants given diphtheria tetanus-pertussis vaccine alone. Total serum anti-PRP antibody responses were analyzed in 336 infants who met strict inclusion criteria. After one, two, or three doses, the respective antibody responses to each of the three lots of PRP-T and to HbOC vaccine were similar. The only exception was one lot of PRP-T, which after one or two injections elicited significantly higher geometric mean antibody responses than the other two lots or the HbOC vaccine. After a third injection, there were no significant lot differences. Combining the data from the different lots, there were no significant differences in the geometric mean antibody concentration after three doses of PRP-T or HbOC (8.3 vs 7.7 micrograms/mL), and 95% and 91%, respectively, of infants had greater than 1.0 microgram/mL of antibody. There were no significant differences in the magnitudes of the respective IgG1-, IgG2-, and IgM-specific antibody concentrations between infants given PRP-T or HbOC. CONCLUSIONS: The three investigational lots of PRP-T tested were safe and were as immunogenic as or more so than the licensed HbOC conjugate vaccine. PMID- 8352218 TI - Hyperinsulinism as a marker in obese children. AB - OBJECTIVE: To determine the relationship between insulin and the metabolic profile and eventual weight loss in obese children. DESIGN: We first attempted to define the metabolic profile for 18 obese children; we then studied weight loss in this group longitudinally. SETTING: Department of Pediatrics in a university hospital. PARTICIPANTS: Eighteen randomly selected, young, obese male subjects from 5 to 16 years of age. INTERVENTIONS: (1) Metabolic screening at the outset, including insulinemia and glycemia after the oral glucose tolerance test and plasma levels of total cholesterol, high-density lipoprotein cholesterol, and triglycerides, and (2) weight loss treatment. RESULTS: We divided the sample into "normoinsulinemic" and "hyperinsulinemic" groups, similar for all the variables tested except for weight loss and plasma triglyceride levels. A direct relationship between weight loss results and duration of treatment was found for the entire group. The "hyperinsulinemic" group had a lower percentage reduction in excess weight, and the results in this group were not dependent on the duration of treatment. CONCLUSIONS: The effort to keep "normoinsulinemic" obese children in treatment may be useful; it is advisable to study "hyperinsulinemic" children more in depth. PMID- 8352219 TI - The immunization status of children with spina bifida. AB - OBJECTIVE: To estimate immunization levels among children with spina bifida and describe factors that may influence immunization completeness. RESEARCH DESIGN: Cross-sectional survey. SETTING: Tertiary care referral center. PATIENTS: One hundred twenty children, from 4 months to 18 years of age, seen in the myelodysplasia clinic of Children's Hospital, Boston, Mass, from February through August 1990. RESULTS: Fifty-eight percent of the children 2 years of age or older and 55% of the children 7 years of age or older had completed the immunization series recommended by the American Academy of Pediatrics. All but one child had an identified primary care provider. Lower immunization levels at 24 months of age occurred in older and in poorer children. Most children (80%) received the first diphtheria and tetanus toxoids and pertussis and oral poliovirus vaccines on time. Immunization delay increased from 20% to 50% through the 18-month diphtheria and tetanus toxoids and pertussis and oral poliovirus vaccines and declined to 24% at school entry. CONCLUSIONS: Many children with spina bifida are underimmunized despite having an identified source of primary care. PMID- 8352221 TI - Diagnostic test ordering in the evaluation of febrile children. Physician and environmental factors. AB - OBJECTIVE: To assess the independent effects of physician and environmental factors on test ordering. METHODS: We prospectively studied 6191 consecutive visits by nonadmitted febrile (rectal temperature > or = 38.0 degrees C) children less than 18 years of age to a children's hospital emergency department from March through November 1989. Multiple logistic regression analysis was used to control for the mutually confounding effects of patient, physician, and environmental factors and to assess attending staff-trainee interactions (effect modification). RESULTS: Patients evaluated by hospital-based subspecialists were significantly more likely to undergo tests than patients evaluated by community based physicians (odds ratio [OR] for undergoing at least one test, 1.13; 95% confidence interval [CI], 1.04 to 1.23; OR for complete blood cell count, 1.28; 95% CI, 1.12 to 1.46). Children seen by physicians with more than 10 years of experience were significantly less likely to undergo tests than those seen by their more junior colleagues, but this effect was modified substantially by trainee presence and level. For example, when children were seen by a physician with more than 10 years of experience and no trainee was involved, the OR for undergoing at least one test was 0.81 (95% CI, 0.73 to 0.91). If the same physician saw the same patient with a junior trainee, the OR for undergoing at least one test was 1.08 (95% CI, 0.95 to 1.24). Patients seen between July and November were significantly more likely to undergo at least one test than those seen between March and June (OR, 1.28; 95% CI, 1.20 to 1.36). CONCLUSIONS: Attending staff, trainee, and seasonal effects on test ordering have important implications for febrile children and their families, for clinical training and supervision, and for health care costs. PMID- 8352220 TI - Advice seeking and appropriate use of a pediatric emergency department. AB - OBJECTIVES: To determine whether seeking advice prior to an unscheduled visit to a pediatric emergency department (PED) influences appropriate use of this setting for minor illnesses. DESIGN: Cross-sectional questionnaire survey. SETTING: The medical emergency department of the Montreal (Quebec) Children's Hospital, a major referral and urban teaching hospital. PARTICIPANTS: Four hundred eighty nine of 562 consecutive parents visiting the PED over two periods, one in February and the other in July 1989. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Parents of children between 0 and 18 years of age visiting the PED were asked whether they had previously sought advice from family, friends, or a physician. Other factors possibly related to the decision to seek care were also measured. Appropriateness was rated, blind to discharge diagnosis, by two pediatricians using a structured series of questions incorporating the child's age, time of the visit, clinical state, and problem at presentation. Thirty-four percent of visits among respondents were judged appropriate. In bivariate analysis, appropriate visits occurred significantly more often when a parent spoke to both a physician and a nonphysician (47%) prior to visiting the PED than when no advice was sought (29%; P < .05). In multivariate analysis, having a regular physician and being one of two children also contributed to appropriateness. CONCLUSIONS: Appropriate use of the PED was positively influenced by seeking prior advice from both a physician and family member, having a regular physician, and having prior child care experience. PMID- 8352222 TI - Controlling malignant melanoma. A focus on pediatricians. AB - There is evidence that the mortality rate associated with malignant melanoma can be decreased by early identification of the risk factors for melanoma and precursor lesions and by reducing sun exposure in young patients at higher risk. Many of the risk factors for malignant melanoma are seen in the pediatric age group. To determine pediatricians' awareness of risk factors for melanoma and their ability to recognize the precursors of melanoma, we studied three departments of pediatrics--at an urban and a suburban medical center and a medical college. Ninety-six members of the audience, which included full-time faculty, practicing pediatricians, and pediatrics residents, responded to questionnaires before and after a presentation on the risk factors for melanoma. Based on the results of the questionnaires, this group of pediatricians believed that they were not sufficiently knowledgeable about the risk factors for melanoma and did not routinely examine their patients for these risk factors or counsel them on proper sunlight protection. These findings indicate a need for making pediatricians aware of the risk factors for melanoma and of the critical role they play in decreasing the incidence and mortality rate associated with this disease. PMID- 8352223 TI - The perspectives of current trainees in combined internal medicine-pediatrics. Results of a national survey. AB - OBJECTIVE: To gather information from combined internal medicine-pediatric residents about their application process for residency, their perceptions of the stressors during residency, and their future plans. DESIGN: Survey of all combined internal medicine-pediatric residents-in-training in the 1989-1990 academic year. PARTICIPANTS: Fifty-four percent of residents-in-training responded to the survey, representing 70% of the programs. RESULTS: Combined residents often investigate and rank other generalist residences. However, internal medicine is significantly (P < .005) considered more often than pediatrics or family medicine. Sixty percent of combined residents do not anticipate further training beyond the 4 years and expect to practice both specialties. The majority of those interested in a subspecialty expect to continue to combine internal medicine and pediatrics in their subspecialty practice. Switching services during the residency engenders stress. Factors that decrease stress include more frequent switches and increasing seniority. Switching from pediatrics to internal medicine is more stressful (P < .0001) than switching to pediatrics from internal medicine. The residents considered ambulatory training sites and a specific coordinator for the program to be the most important features of the residency. CONCLUSIONS: Combined internal medicine pediatric programs continue to attract a small cohort of well-qualified US medical school graduates, the majority of whom intend to practice as generalists in both pediatrics and internal medicine. PMID- 8352224 TI - Habitual physical activity and health-related physical fitness in fourth-grade children. AB - OBJECTIVE: To examine the relationship between habitual physical activity and components of health-related physical fitness in children. DESIGN: Cross sectional survey with correlational analysis. SETTING: Seven public elementary schools in a suburban southern California city. PARTICIPANTS: Five hundred twenty eight healthy fourth-grade children (274 boys and 254 girls), 85% of whom were non-Hispanic whites. Ninety-eight percent of eligible students participated. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Results of six measures of physical activity in children (monitoring by accelerometer, parent report, and child self-reports of weekday activity, weekend activity, and summer involvement in activity classes and youth sports) were combined in a physical activity index. This index of habitual physical activity was examined in relation to measures of five components of health-related fitness: the mile run, skin-fold tests, pull ups, sit-ups, and the sit-and-reach test. The physical activity index was significantly associated with all five fitness components. The canonical correlation was .29. CONCLUSION: Active children appear to engage in a sufficient variety of activities to enhance multiple components of health-related fitness. PMID- 8352225 TI - Radiological cases of the month. Pott's disease in childhood. PMID- 8352226 TI - Radiological cases of the month. The migrating BB and the medicine man. PMID- 8352227 TI - Picture of the month. Neonatal lupus erythematosus. PMID- 8352228 TI - Pathological cases of the month. Myotubular myopathy (centronuclear myopathy). PMID- 8352229 TI - Pathological cases of the month. Type 1 spinal muscular atrophy (Werdnig-Hoffman disease). PMID- 8352230 TI - High Ia (HLA-DR) and low CD11b (Mo1) expression may predict early conversion to leukemia in myelodysplastic syndromes. AB - The FAB classification of myelodysplastic syndromes (MDS) has been useful in predicting prognosis; however, additional methods are required to detect patients at high risk for early conversion to acute nonlymphoblastic leukemia (ANLL). Using a panel of monoclonal antibodies to myelomonocytic surface antigens (MMSA) and flow cytometry, we studied bone marrow cells from 26 patients with MDS of all five FAB subtypes. The MMSA studied included Ia (HLA-DR), CD11b (Mo1), CD14 (Mo2, My4), CD13 (My7), and CD33 (My9). Marrows were considered "positive" for a given MMSA if the percentage of reactive cells exceeded the upper limit of the normal range. Twenty-four of twenty-six patients (92.3%) were CD13 (My7)+, suggesting that CD13 may serve as a diagnostic marker for MDS. Ten of twelve patients who developed ANLL during a median follow-up of 44 weeks were Ia(HLA-DR)+. The Kaplan Meier estimated median time to leukemia (TTL) was 16 weeks for Ia+ patients and 88 weeks for Ia- patients (P = 0.004). All six patients who developed ANLL before 16 weeks from diagnosis were Ia+, while none of the Ia- patients converted to ANLL before 24 weeks. Nine of thirteen patients with low CD11b (Mo1) expression (< 53% reactive cells) developed ANLL, compared with only two of 11 patients with high CD11b expression (> 53% reactive cells). Kaplan-Meier estimated TTL was 29 weeks for patients with low CD11b, compared to 160 weeks for patients with high CD11b (P < 0.05). Patients who met both criteria, Ia+ and low CD11b, represented the poorest prognostic subgroup, with median TTL of 13 weeks compared with 88 weeks for the others (P = 0.017). Ia and CD11b patterns were not specific for MDS subtype, and their expression did not correlate with blast count. These data suggest that MDS patients whose bone marrow cells demonstrate high Ia (HLA-DR) and low CD11b (Mo1) expression represent a poor prognostic subgroup with short TTL. These patients may be candidates for early aggressive or investigational treatment. PMID- 8352231 TI - Decreased erythropoietin responsiveness to iron deficiency anemia in the elderly. AB - The prevalence of anemia in the elderly raises the question of an inappropriate secretion of erythropoietin in response to increased demands. Therefore, the serum erythropoietin concentration of elderly patients (74-95 years) with iron deficiency anemia was measured and compared to that of iron deficiency anemic adults (25-60 years). A lowered erythropoietin secretion in response to anemia was observed in elderly patients in comparison with adults. However, the serum erythropoietin of the anemic elderly was inversely correlated with hemoglobin levels as shown for the anemic adults. The progressive reduction of the renal function observed with aging could explain the decreased capacity of erythropoietin secretion in elderly patients. PMID- 8352232 TI - Comparison of the behavior of normal factor IX and the factor IX Bm variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources. AB - A subset of hemophilia B patients have a prolonged bovine-brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor X present in the sample. The prothrombin time changed as much as 20 seconds when the factor X concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor X concentrations are known. PMID- 8352233 TI - Four years' experience with the treatment of all-trans retinoic acid in acute promyelocytic leukemia. AB - A retrospective analysis was done on 43 patients with acute promyelocytic leukemia (APL) at our hospital from June 1987 to August 1992. All-trans retinoic acid was used to induce these patients to differentiation. In the early period of induction there were risks of severe hemorrhage, which was the main cause of early death. Treatments combined with platelets and heparin or aminomethylbenzoic (PAMBA) were given to patients with abnormal coagulation. As a result only 4 out of 43 patients died of intracranial bleeding at 4-12 days when their white blood cell (WBC) counts peaked. The combination of retinoic acid (RA) and HA chemotherapy could reduce hyperleukocytosis during the RA induction course. None of 7 patients died at early stage with this treatment combination. Our studies showed that it could predict the onset of remission at early stage through observations on the successive changes of karyotypes and morphology of the bone marrow and peripheral blood cells. Our studies also showed that the growth of CFU F could be inhibited by RA. We think that it may play a role in the RA-induced differentiation. In 4 years of follow-up the overall leukemia-free survival (LFS) was 80% with a relapse rate of 45%. Thirty-five patients out of 43 cases were still alive in remission, and one was alive in relapse. All 11 out of 43 patients relapsed within 3 years, but the relapses occurred later, after 3 years duration of remission (P < .01). Retinoic acid failed to induce 5 patients who relapsed with the continuation treatment of RA and chemotherapy alternatively. In order to overcome the resistance to RA, the continuation treatment of simple chemotherapy had been administered following CR. Two cases achieved remission in this way. The difference of resistant events to RA reached significance between these 2 groups of different continuation treatment. PMID- 8352234 TI - Hemostatic study before onset of disseminated intravascular coagulation. AB - Early diagnosis is necessary for the treatment of disseminated intravascular coagulation (DIC), but criteria for the stage preceding the diagnosis of DIC (pre DIC) have not yet been established. To clarify hemostatic abnormalities that occur before the onset of DIC, we performed hemostatic studies in 117 patients within at least a week before the onset of DIC (pre-DIC), in 237 patients with DIC, and in 50 patients without DIC or pre-DIC (non-DIC). Levels of FDP, PT, and fibrinogen, and platelet counts were significantly abnormal after the onset of DIC, but not before. Thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), and FDP-D-dimer levels were significantly higher before the onset of DIC compared to the non-DIC patients. Hemostatic abnormalities were observed within a week before the onset of DIC. Monitoring the plasma levels of TAT, PIC, and FDP-D-dimer might be useful for the diagnosis of a pre-DIC condition. PMID- 8352235 TI - Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult acute lymphoblastic leukemia. AB - Although combination chemotherapy induces complete remission in 60-90% of adults with acute lymphoblastic leukemia, only 20-45% of patients remain in continued remission 5 years from diagnosis. For patients with a short first remission, multiple relapses, or patients with disease refractory to initial induction chemotherapy, few salvage treatments are successful. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of etoposide (100 mg/m2 IV qd x 5), ifosfamide (1.5 g/m2/d x 5), and mitoxantrone (8 mg/m2/d IV x 3) in 11 adult patients with relapsed or refractory ALL. The median follow-up of all patients completing therapy is 208 days (30-484+ days). Eight of 11 (73%; 95% confidence interval 45-92%) achieved a complete remission, two patients failed to enter remission, and one patient died of multiorgan system failure shortly after receiving therapy. Median DFS is 96 days and median survival from remission is 234 days. Five patients who achieved CR subsequently relapsed with a median time to relapse of 80 days (50-151 days). Median time to granulocyte > .5 x 10(9)/L was 28 days (21-46 days) and the median time to platelet recovery > 20 x 10(9)/L was 24 days (21-39 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. These results demonstrate that the combination of etoposide, ifosfamide, and mitoxantrone can be used as an effective salvage therapy for patients with resistant ALL. PMID- 8352236 TI - Decreased affinity and number of transferrin receptors on erythroblasts in the anemia of rheumatoid arthritis. AB - In anemia of chronic disease (ACD) in rheumatoid arthritis (RA) a decreased iron uptake and transferrin binding by erythroblasts are postulated to play a pathophysiological role. To examine whether this is related to changes in transferrin receptor expression by erythroblasts, we studied bone marrow from 5 healthy controls, 5 nonanemic RA patients, and 9 RA patients with ACD. Bone marrow mononuclear cells were incubated with increasing concentrations of 125I transferrin and specific binding data were analyzed by the method of Scatchard. The number of transferrin receptors on erythroblasts from RA patients with ACD was significantly lower as compared to nonanemic RA patients (P < .05) and controls (P < .02). The affinity of the transferrin receptor tended to be lower in ACD. These preliminary data may indicate that transferrin receptor expression by erythroblasts is impaired in ACD. Since the rate of erythroid iron uptake is mainly determined by the number of transferrin binding sites, this may explain a decrease in erythroblast iron availability in ACD in RA. PMID- 8352237 TI - Comparison between interphase and metaphase cytogenetics in detecting chromosome 7 defects in hematological neoplasias. AB - Monosomy 7 (-7) is one of the most common chromosomal abnormalities found in the leukemic cells of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Because patients with -7 have a poor prognosis, their identification is important for treatment planning. Conventionally, -7 is detected by the G-banding technique. This study examines the use of fluorescent in situ hybridization (FISH) methodology to detect -7 cells in interphase nuclei and metaphase chromosomes. Fifteen AML or MDS patients whose leukemic cells were found to have -7 by G-banding at disease presentation were studied. In 13 of these patients, -7 could be detected in interphase by FISH using a chromosome 7 specific centromeric DNA probe. The two patients whose leukemic cells were not detectable by interphase FISH had -7 and t(1q;7p), which were detectable by FISH in metaphase using a chromosome 7-specific painting probe. Metaphase FISH was particularly useful in further defining chromosome 7 defects in cells that contained aberrant or marker chromosomes. For example, in 6 patients, chromosome 7 sequences were detectable in aberrant or marker chromosomes by metaphase FISH, but not by G-banding. These results suggest that metaphase FISH is an important adjunct to conventional cytogenetic methods for defining chromosome 7 abnormalities in AML and MDS patients. Furthermore, interphase FISH is useful for follow-up studies in patients who are found informative for the FISH study at presentation. PMID- 8352238 TI - 8;21 translocation and multilineage involvement. AB - The translocation (8;21)(q22;q22) is commonly associated with acute myeloid leukemia (AML) M2 according to the French-American-British (FAB) classification. We describe 11 cases of t(8;21) diagnosed by strict FAB criteria. Six cases were diagnosed as AML M2, 3 cases as AML M4, 1 case as refractory anemia with excess of blasts in transformation, and 1 case as Philadelphia chromosome negative chronic myeloid leukemia in acceleration. Translocation (8;21) could thus occur in a wider variety of hematological abnormalities. Accordingly, we propose that t(8;21) may involve different hemopoietic lineages. PMID- 8352239 TI - In vivo antimalarial action of a lipophilic iron (III) chelator: suppression of Plasmodium vinckei infection by reversed siderophore. AB - We assessed in vivo antimalarial action of a lipophilic iron (III) chelator belonging to a new synthetic family of biomimetic siderophores previously termed reversed siderophores (RSFs). The family member, RSF ileum2, was chosen for its high membrane permeability and fast irreversible inhibition of human malaria parasite growth in vitro. [Shanzer A, et al., Proc Natl Acad Sci USA 88:6585, 1991 and Lytton SD, et al., Blood 81:214, 1993]. The lipophilic drug was administered to Swiss mice by subcutaneous route in fractionated coconut oil at a dosage of 0.37 g/kg every 8 hr with no adverse reactions observed. After 3-4 injections demonstrable suppression of Plasmodium vinckei petteri infection was observed and an additional 3-4 injections resulted in 2-3-fold lower parasitemia with prolonged survival time over sham-injected control mice. PMID- 8352240 TI - Cell-mediated immune-pancytopenia complicating primary Sjogren's syndrome. AB - A 64-year-old woman with mild bilateral parotid gland swelling and bilateral lower extremity purpura was admitted for evaluation of xerostomia and pancytopenia. The patient had an increased erythrocyte sedimentation rate, pancytopenia, and positive tests for antibodies to nuclear antigen, SS-A, and SS B. Impaired cell-mediated immunity was also present. Bone marrow aspiration showed a hypoplastic marrow with an increased percentage of lymphocytes. A positive Schirmer's test and keratoconjunctivitis were also noted. A diagnosis of primary Sjogren's syndrome was made by sialography and histological salivary gland findings. Therapy with prednisolone improved the pancytopenia. Addition of the patient's peripheral blood mononuclear cells to cultures of bone marrow mononuclear cells derived from a healthy volunteer dose dependently inhibited colony formation, including mixed hemopoietic colonies. On the other hand, addition of the patient's serum failed to inhibit colony formation by normal bone marrow mononuclear cells. These results suggested that one of the causes of pancytopenia in primary Sjogren's syndrome might be mediated by the inhibition of mononuclear cells to the hemopoietic progenitors. PMID- 8352241 TI - Measurement of red blood cell-vitamin B12: a study of the correlation between intracellular B12 content and concentrations of plasma holotranscobalamin II. AB - We have recently reported a new and rapid assay to measure plasma holotranscobalamin II (holo TC II) as a means of exploring vitamin B12 status. In order to further evaluate the significance of plasma holoTC II in determining tissue cobalamin, we have chosen the red blood cell-vitamin B12 (RBC-B12) assay as a measure of tissue vitamin B12 content and studied the relationship between RBC-B12 and plasma holoTC II levels. Plasma holoTC II and RBC-B12 concentrations were concomitantly assayed in 20 hematologically normal controls and cancer patients. In our groups of controls, the mean value of RBC-B12 was determined as 241 +/- 51 pg/ml of packed erythrocytes (PE) with a range varying from 180 to 355 pg/ml PE. Preliminary results obtained in 32 cancer patients revealed lower holoTC II and RBC-B12 levels than the control group and a required threshold value of 70 pg/ml of holoTC II in order to maintain a normal RBC-B12 greater than 180 pg/ml PE. PMID- 8352242 TI - Azidothymidine (AZT)-induced siderosis. AB - Azidothymidine (AZT) interferes with heme synthesis. This should upregulate the synthesis of transferrin receptors and increase the amount of iron taken up by the cell. We found a 50% increase in the iron content of liver and a 20% increase in the iron content of macrophages in AZT-treated mice. PMID- 8352243 TI - Excess iron and catastrophic illness. PMID- 8352244 TI - Primary plasmacytoma of generalized lymph nodes: a long survivor. AB - Extramedullary plasmacytomas are occasionally seen in the course of multiple myeloma; however, primary plasmacytomas are unusual. Most of the primary plasmacytomas arise in the upper respiratory system, but a plasmacytoma of the lymph nodes is very rare. A case of a 56-year-old female with primary plasmacytoma in the lower mandibular, cervical, axillary, and para-aortic lymph nodes accompanied by IgA Kappa paraproteinemia is described. After ten courses of combination chemotherapy with cyclophosphamide and prednisolone, she obtained complete response. However, 6 years later, she had a relapse of plasmacytoma in the generalized lymph nodes. She received ten treatments of melphalan prednisolone and again obtained complete response. She has remained well without chemotherapy or recurrent signs for 9 years. It is considered that conventional chemotherapy can be useful for primary plasmacytoma of generalized lymph nodes. PMID- 8352246 TI - Relapsing polychondritis and myelodysplastic syndrome. PMID- 8352245 TI - Megakaryoblastic transformation of polycythemia vera associated with hypercalcemia. AB - Leukemic transformation is not uncommon in polycythemia vera, particularly after treatment with chemotherapeutic agents. The leukemias that supervene are mostly of myeloid type but megakaryoblastic transformation is distinctly uncommon. We report a case of polycythemia vera terminating in megakaryoblastic leukemia with associated hypercalcemia. PMID- 8352247 TI - Cytochrome B5 reductase deficiency and mental retardation. PMID- 8352248 TI - Renal malacoplakia reappraised. AB - Renal malacoplakia is an unusual form of chronic tubulointerstitial nephritis with a predilection for patients with recurrent urinary tract infections and an immunocompromised state. Its characteristic feature is the parenchymal infiltration by macrophages with ample cytoplasm containing abundant periodic acid-Schiff-positive granules, known as von Hansemann cells, and the presence of diagnostic extracytoplasmic or intracytoplasmic calcospherites, known as Michaelis-Gutmann bodies. Renal malacoplakia is more common in women (female to male ratio 3:1), in whom the lesions develop in a younger age group (third to fifth decade) than in men (over 50 years). Enlarged kidneys in the presence of persistent urinary infection should lead to the consideration of this entity. The diagnosis can only be established by pathologic examination of renal tissue. Renal biopsy early in the course of the disease is essential since in an increasing number of cases medical therapy has resulted in resolution of the disease process and preservation of renal function. PMID- 8352249 TI - Clinical significance of antineutrophil cytoplasmic autoantibodies with specificity for lactoferrin in renal diseases. AB - The prevalence and clinical significance of antineutrophil cytoplasmic antibodies with specificity for lactoferrin was determined in patients with renal diseases. Antilactoferrin antibodies were found in only 12 of 920 patients (1.3%). These patients had either "pauci-immune" necrotizing crescentic glomerulonephritis (three cases) or lupus nephritis (nine cases). To verify whether antilactoferrin antibodies were specific for patients with systemic lupus erythematosus (SLE) and renal involvement, we studied 61 additional lupus patients, 40 with active lupus nephritis and 21 with active SLE and no renal involvement. Antilactoferrin antibodies were found in approximately 15% to 20% of patients with SLE, irrespective of the presence of renal involvement. We conclude that antineutrophil cytoplasmic antibodies with specificity for lactoferrin are only sporadically found in patients with renal diseases; these patients have either necrotizing crescentic glomerulonephritis or lupus nephritis. However, antilactoferrin antibodies are not a marker for renal involvement in SLE. PMID- 8352250 TI - Insurability for asymptomatic hematuria or proteinuria during childhood. AB - The objective of this survey was to describe life insurance underwriting practices concerning children with asymptomatic hematuria and proteinuria. A questionnaire was sent to 200 companies licensed to issue life insurance policies in the state of New York. The medical director of each company was asked to respond to the insurability of children with asymptomatic hematuria and proteinuria. Two case summaries were provided with the questionnaire. Of 97 companies, 66 would offer insurance to the patient with hematuria, although 38 (58%) would charge additional premiums. In response to the problem of proteinuria, 61 companies would offer life insurance, although 50 (82%) would require higher premium charges (P < 0.002 compared with hematuria). We conclude that children with asymptomatic hematuria and proteinuria can usually obtain life insurance, although often at higher cost. Invasive diagnostic tests are not necessary for insurers to offer insurance. PMID- 8352251 TI - Plasma exchange in children with hemolytic-uremic syndrome at risk of poor outcome. AB - A retrospective study on the use of plasma exchange in children with hemolytic uremic syndrome was conducted to compare the renal outcome in treated and nontreated patients. Only children over 5 years of age were selected because they seem to be at major risk of bad renal prognosis. The evolution of renal function in the two populations is not significantly different, but chronic renal failure (clearance < 60 mL/min/1.73 m2) and end-stage renal failure were present only in untreated patients. PMID- 8352252 TI - Linear estimates of variable-volume, single-pool Kt/V: an analysis of error. AB - Two linear approximations of variable-volume, single-pool Kt/V were compared. Each is based on the corrected postserum/preserum urea nitrogen ratio (R), called R', where R' = R - 0.03 - UF/W (UF/W being the ratio of the ultrafiltrate volume removed to the postdialysis weight). The two formulas were derived by construction of tangents to the exponential curve y = -In(R') at approximately 1.0 and 1.3, namely, y = 2 - 2.7(R') and y = 2.2 - 3.3(R'), respectively. The linear formulas were compared with each other and to our previous logarithmic formula -In(R - 0.008*t - UF/W). All were compared with the modeled Kt/V using a variable-volume, single-pool kinetic model in 500 dialysis sessions, with Kt/V ranging from 0.7 to 2.1. Analysis of error uncovered systematic errors in all the formulas. However, each of the new linear formulas had very little systematic error in the Kt/V range it was designed for, over a span of 0.6 - 0.7 Kt/V units. Outside this range the linear formulas underestimate the variable-volume, single pool modeled Kt/V, but, barring two-pool or other technical errors, they do not markedly overestimate Kt/V in any Kt/V range. The total error with the new linear formulas was an acceptable 5%, in the range they were designed for. The results suggest that precise estimates of Kt/V can be derived using linear formulas as long as a given Kt/V range is targeted. PMID- 8352253 TI - Atherogenic lipids and lipoproteins in hemodialysis patients. AB - Dyslipidemia may contribute to atherosclerosis in hemodialysis patients. While hypertriglyceridemia is relatively common in this population, hypercholesterolemia is not. Since abnormalities in various plasma cholesterol fractions and lipoproteins have been associated with an increased incidence of cardiovascular disease in the nonuremic population, we examined these abnormalities to determine whether they occur in patients with chronic renal failure. Twenty-four patients on maintenance hemodialysis were studied. We found that, despite relatively low plasma total cholesterol levels, a substantial number of patients had low high-density lipoprotein cholesterol, low apolipoprotein AI, and high apolipoprotein B levels. Furthermore, approximately 40% and 30%, respectively, of the patients had elevated plasma levels of lipoprotein(a) and remnants of chylomicron and very low-density lipoprotein. Lipoprotein(a) levels could not be predicted from any of the variables that were studied. The abnormal plasma levels of these potentially atherogenic lipids and lipoproteins suggest that they may contribute to the high incidence of cardiovascular diseases in the hemodialysis population. PMID- 8352255 TI - Comparison of first use and reuse of cuprophan membranes on interleukin-1 receptor antagonist and interleukin-1 beta production by blood mononuclear cells. AB - The magnitude of the changes in a variety of blood constituents on exposure to the dialysis membrane has been used as an index of "biocompatibility," and dialyzer reuse has been postulated to improve biocompatibility by attenuating these changes. We studied the hemodialysis-induced changes in the in vitro production of interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1 beta (IL-1 beta) by peripheral blood mononuclear cells (PBMCs), and compared the effect of first use and reuse of cuprophan membranes on these changes. Studies were performed during dialysis with first use and third reuse of the same kidney. The cell content and production of IL-1Ra and IL-1 beta by unstimulated and endotoxin- or IgG-stimulated PBMCs were studied just prior to dialysis, and from the afferent and efferent limbs of the blood circuit 15 minutes after the start of dialysis. Interleukin-1 receptor antagonist and IL-1 beta were measured by specific radioimmunoassay and are expressed as picograms per 2.5 x 10(6) PBMCs. Fifteen minutes after the start of dialysis, the number of PBMCs harvested from 10 mL of blood decreased from 19.8 +/- 4.7 x 10(6) predialysis to 14 +/- 3 x 10(6) (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352254 TI - Uremic myopathy limits aerobic capacity in hemodialysis patients. AB - Eleven end-stage renal disease patients trained by stationary cycling during their hemodialysis treatments. After a 6-week control period, 12 weeks of training began and was increased to 30 to 60 minutes at > or = 70% of peak heart rate. Baseline, pretraining and, posttraining exercise tests were performed. Workload (WL), oxygen uptake (VO2peak), cardiac output (Q), heart rate (HR), and arterial oxygen content (CaO2) were measured. Stroke volume (SV), arteriovenous oxygen difference ((a-v)O2), and mixed-venous oxygen content (CvO2) were calculated. Rectus femoris biopsies were obtained pretraining and posttraining. At peak exercise, WL increased from 60 +/- 4 to 70 +/- 6 W (P < 0.05), VO2peak showed an upward trend from 14.8 +/- 0.9 to 16.8 +/- 1.3 mL/kg/min (P < 0.1), and Q, HR, SV, CaO2, CvO2, and (a-v)O2 were unchanged. Ten of the 11 patients increased WL, but only six increased VO2peak (five of 11 patients decreased VO2peak). The difference between groups (P < 0.02) was attributable to (a-v)O2, which increased in those who increased VO2peak (P < 0.02). There was an upward trend for succinate dehydrogenase activity (P < 0.06), and phosphofructokinase activity increased (P < 0.05). However, the rectus femoris capillary to fiber ratio, type I and II fiber areas, and fiber area variability were unchanged, and neither histomorphologic nor enzymatic activity changes were related to change in VO2peak. We conclude that not all dialysis patients increase VO2peak after training, but most can improve exercise capacity. Patients who improved VO2peak widened their (a-v)O2 difference, increasing oxygen extraction and showing that oxygen delivery is not always the limiting factor. Thus, the limitation of VO2peak in dialysis patients is a complex interaction of central and peripheral factors. Muscle therapies, such as exercise training, are needed in addition to increased oxygen delivery in rehabilitation of dialysis patients. PMID- 8352256 TI - Gentamicin clearance during hemodialysis: a comparison of high-efficiency cuprammonium rayon and conventional cellulose ester hemodialyzers. AB - The advent of high-efficiency hemodialyzers has afforded improved efficiency of urea clearance; however, increased clearance of other substances, particularly antibiotics, also may occur, necessitating changes in clinical practice. Accordingly, we compared the efficiency of gentamicin removal using two different hemodialyzers, a conventional saponified cellulose ester (CD 135) and a high efficiency cuprammonium rayon dialyzer (TAF 175L), in eight hospitalized patients undergoing antibiotic therapy for suspected or proven gram-negative infection. The rate of dialysis, estimated as the ratio of dialyzer urea clearance (K) to urea distribution volume (V) (K/V urea), and the total elimination rate constant (k) of gentamicin were measured during 17 hemodialysis treatments. The K/V urea for the two dialyzers, TAF 175L and CD 135, was 0.390 +/- 0.024 hr-1 and 0.413 +/ 0.129 hr-1 (P = NS), respectively. The TAF 175L hemodialyzer was almost twice as efficient in removing gentamicin as the CD 135: TAF 175, k = 0.263 +/- 0.024 hr 1; CD 135, k = 0.132 +/- 0.027 hr-1 (P < 0.001). Moreover, the rate of dialysis (K/V urea) was correlated with k of gentamicin for the TAF 175L dialyzer (r2 = 0.50, P < 0.02) but not for the CD 135 dialyzer. We conclude that dialyzer characteristics and the rate of dialysis (K/V urea) should be taken into consideration when determining the dosage of gentamicin in patients on hemodialysis. PMID- 8352257 TI - Maintenance of bone mass in patients receiving dialytic therapy. AB - To determine what factors contribute to and change bone mineral density (BMD) in dialysis patients, serial lumbar spine dual x-ray absorptiometry studies were analyzed by stepwise regression analysis in 67 black dialysis patients. The patients were 50.5 +/- 2.0 years of age (mean +/- SE) and 49% were men; the patients had received dialytic therapy for 3.7 +/- 0.5 years. The mean initial BMD z-score was 0.147 +/- 0.182. By cross-sectional analysis, the BMD increased in the male and premenopausal female patients but decreased in the postmenopausal female patients by 2.5% g/cm2/decade of life, less than that observed in black patients with normal renal function. Univariate analysis and stepwise regression analysis demonstrated radiographic evidence of osteopenia (beta-coefficient = 0.180 +/- 0.050; P = 0.001) and prior parathyroidectomy (beta-coefficient = 0.133 +/- 0.070; P = 0.054) as the only variables significantly correlated to the BMD. The effects of biochemical variables and different treatments on the delta BMD, calculated as the difference between each patient's first and second BMDs divided by the interval in years, were evaluated by stepwise regression analysis in 41 patients. The mean interval between the two BMDs was 18.4 +/- 1.02 months (range, 5 to 34 months) and the delta BMD was 0.025 +/- 0.018 g/cm2/yr, increasing in 65% of the patients. By univariate and stepwise regression analysis, the mean monthly serum total alkaline phosphatase concentration was the only variable that correlated with the delta BMD (beta-coefficient = 0.0001; P = 0.030).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352258 TI - Evidence for increased cancer deaths in chronic dialysis patients. AB - We analyzed longitudinal data on the cancer mortality rate in chronic dialysis patients and in the general population in Okinawa, Japan. In the general population from 1980 to 1990, the mortality rate has been stable at approximately 1.300 males and 0.897 females per thousand persons year, the male to female ratio being 1.45. In the period from 1971 to 1990, we found 91 (4.6%) patients with cancer in a group of 1,982 (824 females and 1,158 males) chronic dialysis patients; forty-nine of the 91 patient (53.8%) died by April 1, 1991. Using the standard mortality rate in the general population, which was obtained for each sex and age class (0 to 34 years, 35 to 44 years, 45 to 54 years, 55 to 64 years, and > or = 65 years), we calculated the relative risk of death from cancer in dialysis patients. The risk ratio in dialysis patients was significantly increased, being 2.48 (P < 0.05) for males and 3.99 (P < 0.05) for females. The mean (+/- SEM) age at the time of death from cancer in the dialysis group was 60.1 +/- 2.0 years in the males and 60.1 +/- 2.1 years in the females; the males were 6.3 years younger than the general population and the females were 9.3 years younger. The proportion of patients with colon cancer (both sexes) and cancer of the uterus and breast (females) was higher in the dialysis patients than in the general population. PMID- 8352259 TI - Extrarenal effect of cyclosporine A on potassium homeostasis in renal transplant recipients. AB - Cyclosporine A (CyA) is known to cause hyperkalemia by impairing renal potassium excretion. However, the observation of transient and severe hyperkalemia occurring within 3 to 5 hours of CyA ingestion in several organ transplant patients led us to postulate that it might also cause a potassium efflux from the intracellular to the extracellular fluid space. We tested this hypothesis by studying 22 nondiabetic, renal transplant patients with stable renal function (serum creatine < 2.25 mg/dL) who were treated with CyA (CyA group; n = 14) or imuran and prednisone (STD group; n = 8). Eight CyA and four STD patients also were treated with a beta-blocker (BB). While at rest, fasting plasma potassium levels were sampled hourly in all patients from 8:00 am to 1:00 pm. All medications (including CyA and BBs) were given after the 8:00 am blood sampling. Venous pH, osmolality, insulin, aldosterone, epinephrine, norepinephrine, and CyA levels also were determined at 8:00 am, 11:00 am, and 1:00 pm. Urine was collected from 11:00 pm to 8:00 am prior to the study (period I) and from 8:00 am to 1:00 pm during the study (period II) for measurement of potassium excretion (standardized to a 5-hour period). A significant increase in serial plasma potassium levels was noted in the CyA + BB group only (P = 0.0006 by repeated measures analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352260 TI - Prevalence and long-term outcome of glomerulonephritis in renal allografts. AB - We report long-term results over 10 years in patients developing glomerulonephritis after renal transplantation. The prevalence rate of glomerulonephritis was 6.2% in 785 renal transplants involving 697 patients with end-stage renal disease. This rate was 14% in patients undergoing biopsy of their grafts because of malfunction. The rate was 15% in patients diagnosed as having glomerulonephritis of any cause prior to transplantation. Membranous, focal sclerosing, and IgA glomerulonephritis were the most common histologic diagnoses. Documented histologic recurrence occurred in only 1% of patients with poor, biopsy-proven glomerulonephritis of their native kidneys. Patients with focal sclerosing glomerulonephritis had the greatest risk from recurrence. De novo glomerulonephritis was most likely to be membranous in character. The graft survival rate of patients with glomerulonephritis was not distinguishable from that of patients showing rejection; both were 45% at 60 months and 33% versus 11%, respectively, at 120 months (P = NS); the graft survival rate in patients without rejection was 76% at 120 months. Thus, glomerulonephritis is responsible for approximately 14% of renal graft malfunction. Glomerulonephritis has a prognosis similar to chronic rejection. Finally, glomerulonephritis as specific histologic recurrence is unusual. Patients with glomerulonephritis should not be discouraged from undergoing transplantation because of putative risks related to recurrence. PMID- 8352261 TI - Abrogation of MRL/lpr lupus nephritis by dietary flaxseed. AB - A diet supplemented with flaxseed, rich in alpha-linolenic acid and plant lignans (the latter, potent platelet-activating factor receptor antagonists), was tested in a murine model of lupus nephritis. MRL/lpr female mice (n = 25) were fed 15% flaxseed diet for 14 weeks commencing at 10 weeks of age. As controls, 30 MRL/lpr mice received a standard rodent diet without flaxseed. Isotope-glomerular filtration rate (14C-inulin clearance) was measured at 9, 16, and 24 weeks of age. Proteinuria was assessed at 2-week intervals. Spleen lymphocyte proliferation, quantitated by DNA analysis, was evaluated using flow cytometry at 9, 13, 19, and 21 weeks of age. Mortality was recorded throughout the study. Glomerular filtration rate at 16 weeks was greater in flaxseed-fed mice (0.15 +/- 0.03 mL/min) compared with controls (0.06 +/- 0.04 mL/min; P = 0.01). The onset of proteinuria (Albustix, Ames Division, Miles Laboratories, Rexdale, Ontario, Canada; > or = 2+) was delayed by 4 weeks in the flax-treated mice. The percentage of flaxseed-fed mice with proteinuria was lower than the control mice up to 21 weeks of age (39% v 58%; P = 0.01). Spleen lymphocyte proliferation (percentage of cells in S-phase) at 13 weeks of age was significantly higher in the control group (22.9 +/- 5.0, P = 0.01) but not in the flaxseed group (17.2 +/ 4.9) compared with baseline (9 weeks of age) values (13.0 +/- 3.5). Mortality was lower in the flaxseed-fed mice versus the control mice (assessed by Mantel Haenszel (log-rank) test; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352262 TI - Ranitidine-associated interstitial nephritis and Fanconi syndrome. AB - Ranitidine is an H2 blocking agent widely used in the treatment of peptic ulcer disease. Although acute interstitial nephritis has been described in association with a related drug, cimetidine, this complication secondary to ranitidine has been reported only once before. We describe a patient who presented with acute renal failure and features of Fanconi syndrome in association with the use of ranitidine. Renal biopsy showed acute interstitial nephritis. The patient had renal tubular acidosis with alkaline urine, aminoaciduria, renal glycosuria, uricosuria, and phosphaturia. There was a marked disparity between the degree of elevation of urea nitrogen and creatinine concentrations in the serum that was attributable to diminished urea generation, since simultaneous measurement of inulin, creatinine, and urea clearances showed that they were comparably reduced. Urinary nitrogen loss in the form of aminoaciduria contributed significantly to decreased urea generation. Both acute renal failure and Fanconi syndrome resolved after treatment with prednisone. PMID- 8352263 TI - Ranitidine-induced acute interstitial nephritis with epithelial cell foot process fusion. AB - Although acute interstitial nephritis has been well described with the histamine H2-receptor antagonist cimetidine, we found only one previous case report of ranitidine-induced interstitial nephritis in the literature. We describe an additional patient who developed acute interstitial nephritis after taking ranitidine. Electron microscopy showed focal fusion of the epithelial cell foot processes that was not described in the previous report of ranitidine-induced interstitial nephritis. PMID- 8352264 TI - Simultaneous "in series" hemodialysis and hemoperfusion in the management of valproic acid overdose. AB - There is little published experience with the extracorporeal treatment of valproic acid overdose, although the pharmacokinetic properties of valproic acid suggest a potential role for hemodialysis and/or hemoperfusion. At therapeutic concentrations valproic acid is highly protein bound, but at the higher concentrations seen in the overdose setting binding sites become saturated and free valproic acid should be subject to removal by hemodialysis. We report the case of a patient with serious toxicity secondary to valproic acid overdose who was successfully treated with a combination of hemodialysis and hemoperfusion. With this treatment the half-life of valproic acid was reduced from a predialysis level of 13 hours to 1.7 hours, with rapid lowering of valproic acid levels and dramatic clinical improvement. Based on our experience in this patient and a review of previously reported cases, hemodialysis should be considered in the treatment of valproic acid overdose. PMID- 8352265 TI - Acute renal allograft dysfunction in the setting of deep venous thrombosis: a case of successful urokinase thrombolysis and a review of the literature. AB - Acute renal allograft vein thrombosis is a rare but serious complication of renal transplantation. When occurring in the early posttransplant period it is usually associated with surgical complications and often results in the loss of the graft. At later stages, when graft function has stabilized, its development may then be associated with underlying disorders such as glomerulonephritis, immunosuppressive therapy, increased hematocrit, acute rejection, or extension of lower extremity venous thromboses. We report a case of acute allograft dysfunction occurring in the setting of extensive deep vein thrombosis. In our patient, thrombosis in the setting of acute graft tenderness and swelling, anuria, and an increasing creatinine strongly suggest a diagnosis of acute allograft renal vein thrombosis. We describe a successful reversal of acute renal failure through urokinase thrombolysis and review the current literature on the use of thrombolytic agents for the treatment of acute renal allograft vein thrombosis. PMID- 8352266 TI - Membranous nephropathy associated with renal cell carcinoma. PMID- 8352268 TI - Intravenous versus subcutaneous dosing of epoetin: a review of the literature. AB - Recombinant human erythropoietin (epoetin) is approved to be administered by the intravenous (i.v.) or subcutaneous (SC) route. Several studies have been conducted and published that compare the relative pharmacokinetics and efficacy of the IV and SC routes. An analysis of the methodology and results of these studies reveals that the data have been somewhat contradictory and highly variable. However, most investigations have concluded that the SC route is associated with a decreased dose requirement in the correction and/or maintenance phase. To justify a switch from the i.v. to the SC route, it is important to consider the practical implications, including patient and staff acceptance, as well as the financial aspects. Regardless of the route of administration, dose titration must be individualized based on the patient's response to epoetin therapy, red blood cell turnover rate, and iron status. More studies are needed to develop a standardized cost-effective method for epoetin dosing in patients on dialysis. PMID- 8352267 TI - Optimizing epoetin therapy in end-stage renal disease: the case for subcutaneous administration. AB - The effectiveness of various recombinant human erythropoietin (epoetin) administration routes and dosage schedules in patients on dialysis was studied. The mean dose required to achieve and maintain a hematocrit level between 33% and 40% is 225 U/kg/wk when administered intravenously (i.v.) in three divided doses. A once-weekly i.v. schedule requires a dose of 429 U/kg/wk to maintain the same target hematocrit. In contrast, the required epoetin dose is reduced by an average of 25% to 50% when administered via the subcutaneous (SC) route. Analysis of data from 25 dialysis centers shows that SC epoetin administration resulted in higher normalized responses than i.v. administration. The hematocrit response in patients at these centers was proportional to the weekly dose, with a greater slope in those centers using predominantly SC as compared with i.v. dosing. Cost analysis indicates that the use of SC dosing two or three times weekly at an average total weekly dose of 120 U/kg is effective for the treatment of anemia in most patients on dialysis. PMID- 8352269 TI - National Cooperative rHu Erythropoietin Study in patients with chronic renal failure--an interim report. The National Cooperative rHu Erythropoietin Study Group. AB - This second interim report of the National Cooperative rHu Erythropoietin Study presents data from 324 patients new to recombinant human erythropoietin (Epoetin alfa) who completed at least 12 months of study participation. Mean hematocrit levels increased to approximately 30% by month 3 in patients on hemodialysis (n = 293) and stabilized for the remainder of the study whether Epoetin alfa was administered by the intravenous (n = 250) or subcutaneous (n = 42) route. The intravenous dosage level ranged between 106.9 and 121.6 U/kg/wk; subcutaneous dosing ranged between 87.4 and 108.0 U/kg/wk; dosing levels in patients on peritoneal dialysis (n = 31) were similar, although there was a trend towards slightly higher hematocrit levels. Throughout the 12 months of the study, there was no relationship between blood pressure and either hematocrit level or Epoetin alfa dose. Approximately two thirds of the patients were receiving iron supplementation at any given time, and there was a trend towards the increased use of oral iron supplements. The incidence of adverse events in this cohort of patients was low throughout the study, and there was no relationship between the incidence of adverse events and either hematocrit level or Epoetin alfa dose. Based on an analysis of data from baseline to first follow-up, Epoetin alfa therapy resulted in improvement in several quality-of-life factors, most notable of which was vitality. Improvement occurred in all patient subgroups with some variability in the level and intensity of effect. Overall, these data demonstrate that Epoetin alfa therapy is safe and effective when used in a broad cross section of patients on dialysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352270 TI - Facility reimbursement: a critical comparison between hemodialysis and peritoneal dialysis. AB - The population of patients on dialysis in the United States is growing at between 8% and 9% annually. The increasing patient load places a burden on existing dialysis facility capacity and creates a challenge for physicians and administrators to meet patient demand in the future. Increasing costs, reductions in reimbursement, and volatile regulatory policy have increased the risks associated with operating and investing in dialysis facilities. It is important that administrators and physicians understand the economics associated with the modalities available to treat patients on dialysis and that they incorporate this understanding into their planning for the future. PMID- 8352271 TI - mtDNA sequences suggest a recent evolutionary divergence for Beringian and northern North American populations. AB - Conventional descriptions of the pattern and process of human entry into the New World from Asia are incomplete and controversial. In order to gain an evolutionary insight into this process, we have sequenced the control region of mtDNA in samples of contemporary tribal populations of eastern Siberia, Alaska, and Greenland and have compared them with those of Amerind speakers of the Pacific Northwest and with those of the Altai of central Siberia. Specifically, we have analyzed sequence diversity in 33 mitochondrial lineages identified in 90 individuals belonging to five Circumpolar populations of Beringia, North America, and Greenland: Chukchi from Siberia, Inupiaq Eskimos and Athapaskans from Alaska, Eskimos from West Greenland, and Haida from Canada. Hereafter, we refer to these five populations as "Circumarctic peoples." These data were then compared with the sequence diversity in 47 mitochondrial lineages identified in a sample of 145 individuals from three Amerind-speaking tribes (Bella Coola, Nuu-Chah-Nulth, and Yakima) of the Pacific Northwest, plus 16 mitochondrial lineages identified in a sample of 17 Altai from central Siberia. Sequence diversity within and among Circumarctic populations is considerably less than the sequence diversity observed within and among the three Amerind tribes. The similarity of sequences found among the geographically dispersed Circumarctic groups, plus the small values of mean pairwise sequence differences within Circumarctic populations, suggest a recent and rapid evolutionary radiation of these populations. In addition, Circumarctic populations lack the 9-bp deletion which has been used to trace various migrations out of Asia, while populations of southeastern Siberia possess this deletion. On the basis of these observations, while the evolutionary affinities of Native Americans extend west to the Circumarctic populations of eastern Siberia, they do not include the Altai of central Siberia. PMID- 8352272 TI - Chromosome 14 and late-onset familial Alzheimer disease (FAD). AB - Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected pedigree-member (APM), and sib-pair analyses were used, in 49 families with a mean age at onset > or = 60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score < or = -2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P < .02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset > or = 60 years and < 70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. PMID- 8352273 TI - De novo microdeletion on an inherited Robertsonian translocation chromosome: a cause for dysmorphism in the apparently balanced translocation carrier. AB - Robertsonian translocations are usually ascertained through abnormal children, making proposed phenotypic effects of apparently balanced translocations difficult to study in an unbiased way. From molecular genetic studies, though, some apparently balanced rearrangements are now known to be associated with phenotypic abnormalities resulting from uniparental disomy. Molecular explanations for other cases in which abnormality is seen in a balanced translocation carrier are being sought. In the present paper, an infant is described who has retarded growth, developmental delay, gross muscular hypotonia, slender habitus, frontal bossing, micrognathia, hooked nose, abundant wispy hair, and blue sclerae. Cytogenetically, she appeared to be a carrier of a balanced, paternally derived 14;21 Robertsonian translocation. Analysis of DNA polymorphisms showed that she had no paternal allele at the D14S13 locus (14q32). Study of additional DNA markers within 14q32 revealed that her previously undescribed phenotype results from an interstitial microdeletion within 14q32. Fluorescent in situ hybridization was used to show that this microdeletion had occurred de novo on the Robertsonian translocation chromosome. These observations may reactivate old suspicions of a causal association between Robertsonian translocations and de novo rearrangements in offspring; a systematic search for similar subcytogenetic rearrangements in other families, in which there are phenotypically abnormal children with apparently balanced translocations, may be fruitful. The clinical and molecular genetic data presented also define a new contiguous gene syndrome due to interstitial 14q32 deletion. PMID- 8352274 TI - Individual DNA identification from ancient human remains. AB - Individual identification of ancient human remains is one of the most fundamental requisites for studies of paleo-population genetics, including kinship among ancient people, intra- and interpopulation structures in ancient times, and the origin of human populations. However, knowledge of these subjects has been based mainly on circumstantial archaeological evidence for kinship and intrapopulation structure and on genetic studies of modern human populations. Here we describe individual identification of ancient humans by using short-nucleotide tandem repeats and mtDNAs as genetic markers. The application of this approach to kinship analysis shows clearly the presence or absence of kinship among the ancient remains examined. PMID- 8352275 TI - Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myoclonic epilepsy: no evidence for an epilepsy locus in the HLA region. AB - Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6S89, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype. PMID- 8352276 TI - Influence of genotype-dependent effects of covariates on the outcome of segregation analysis of the body mass index. AB - Several recent studies of the body mass index (BMI) have provided support for a recessive major gene influencing heaviness in humans. Segregation analysis of the BMI was carried out recently in a series of randomly sampled French-Canadian families to determine whether we could replicate the major gene finding by using a residual phenotype adjusted for the effects of age and sex. The best model included a recessive major effect for high BMI values with residual familial resemblance; however, Mendelian transmission could not be confirmed, and the no transmission hypothesis (where all the tau's are constrained to be equal) was not rejected. Considering that the BMI is a complex phenotype affected by many factors and that there are known variations in body composition during growth and aging, we undertook a reanalysis of the data, using a model that allowed the estimation of genotype-specific age and gender effects. New tests on the transmission parameters satisfy the criteria for interfering Mendelian segregation. The results suggest that individuals with the "high" recessive genotype show the greatest degree of heaviness at birth, with a subsequent trend toward lower values throughout life, while individuals with the dominant "normal" genotypes show no appreciable trends with age. In addition, the "high" genotype appears to confer a greater degree of heaviness in females as compared with males. These results, along with other observations from the data, suggest that, while a recessive single gene influence may be discernible, the phenotypic expression of the BMI is likely to be complicated by genotype x environment interactions and, possibly, by the action of other loci. Further, the data also are consistent with the hypothesis that modifying factors may include the adoption of a more prudent life-style by individuals genetically predisposed to heaviness and a secular increase in the incidence, prevalence, and potency of environmentally based triggers leading to a higher penetrance of the "heavy" genotype in the young. PMID- 8352277 TI - Detection of cryptic chromosomal abnormalities in unexplained mental retardation: a general strategy using hypervariable subtelomeric DNA polymorphisms. AB - Given the availability of DNA from both parents, unusual segregation of hypervariable DNA polymorphisms (HVPs) in the offspring may be attributable to deletion, unbalanced chromosomal translocation, or uniparental disomy. The telomeric regions of chromosomes are rich in both genes and hypervariable minisatellite sequences and may also be particularly prone to cryptic breakage events. Here I describe and analyze a general approach to the detection of subtelomeric abnormalities and uniparental disomy in patients with unexplained mental retardation. With 29 available polymorphic systems, approximately 50%-70% of these abnormalities could currently be detected. Development of subtelomeric HVPs physically localized with respect to their telomeres should provide a valuable resource in routine diagnostics. PMID- 8352278 TI - Statistical evaluation of multiple-locus linkage data in experimental species and its relevance to human studies: application to nonobese diabetic (NOD) mouse and human insulin-dependent diabetes mellitus (IDDM). AB - Common, familial human disorders generally do not follow Mendelian inheritance patterns, presumably because multiple loci are involved in disease susceptibility. One approach to mapping genes for such traits in humans is to first study an analogous form in an animal model, such as mouse, by using inbred strains and backcross experiments. Here we describe methodology for analyzing multiple-locus linkage data from such experimental backcrosses, particularly in light of multilocus genetic models, including the effects of epistasis. We illustrate these methods by using data from backcrosses involving nonobese diabetic mouse, which serves as an animal model for human insulin-dependent diabetes mellitus. We show that it is likely that a minimum of nine loci contribute to susceptibility, with strong epistasis effects among these loci. Three of the loci actually confer a protective effect in the homozygote, compared with the heterozygote. Further, we discuss the relevance of these studies for analogous studies of the human form of the trait. Specifically, we show that the magnitude of the gene effect in the experimental backcross is likely to correlate only weakly, at best, with the expected magnitude of effect for a human form, because in humans the gene effect will depend more heavily on disease allele frequencies than on the observed penetrance ratios; such allele frequencies are unpredictable. Hence, the major benefit from animal studies may be a better understanding of the disease process itself, rather than identification of cells through comparison mapping in humans by using regions of homology. PMID- 8352279 TI - Nondisjunction of chromosome 15: origin and recombination. AB - Thirty-two cases of uniparental disomy (UPD), ascertained from Prader-Willi syndrome patients (N = 27) and Angelman syndrome patients (N = 5), are used to investigate the pattern of recombination associated with nondisjunction of chromosome 15. In addition, the meiotic stage of nondisjunction is inferred by using markers mapping near the centromere. Two basic approaches to the analysis of recombination are utilized. Standard methods of centromere mapping are employed to determine the level of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recombinant class (i.e., zero, one, two, three, or more observable crossovers) is compared with expected values. This is useful for testing whether the reduction in recombination can be attributed solely to a proportion of cases with no recombination at all (because of asynapsis), with the remaining groups showing normal recombination (or even excess recombination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-recombinant classes, with a corresponding increase in both the zero- and one-recombinant classes over expected values. The majority, more than 82%, of the extra chromosomes in maternal UPD(15) cases are due to meiotic I nondisjunction events. In contrast, most paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra paternal chromosome. PMID- 8352280 TI - Functional studies of a germ-line polymorphism at codon 47 within the p53 gene. AB - A rare germ-line polymorphism in codon 47 of the p53 gene replaces the wild-type proline (CCG) with a serine (TCG). Restriction analysis of 101 human samples revealed the frequency of the rare allele to be 0% (n = 69) in Caucasians and 4.7% (3/64, n = 32) among African-Americans. To investigate the consequence of this amino acid substitution, a cDNA construct (p53 mut47ser) containing the mutation was introduced into a lung adenocarcinoma cell line (Calu-6) that does not express p53. A growth suppression similar to that obtained after introduction of a wild-type p53 cDNA construct was observed, in contrast to the result obtained by introduction of p53 mut143ala. Furthermore, expression of neither p53 mut47ser nor wild-type p53 was tolerated by growing cells. In transient expression assays, both mut47ser and wild-type p53 activated the expression of a reporter gene linked to a p53 binding sequence (PG13-CAT) and inhibited the expression of the luciferase gene under the control of the Rous sarcoma virus promoter (RSVluc). In the same assay, mut143ala did not activate the expression of PG13-CAT and produced only a slight inhibitory effect on RSVluc. These findings indicate that the p53 variant with a serine at codon 47 should be considered as a rare germ-line polymorphism that does not alter the growth suppression activity of p53. PMID- 8352281 TI - Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: linkage and loss of heterozygosity. AB - Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North American and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCS gene is probably a tumor-suppressor gene. In this study we have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity. We have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls. PMID- 8352283 TI - Better data analysis through data exploration. PMID- 8352282 TI - Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism. AB - Hyperphenylalaninemias represent a major class of inherited metabolic disorders. They are most often caused by mutations in the phenylalanine hydroxylase gene and, less frequently but with usually more serious consequences, in genes necessary for the synthesis and regeneration of the cofactor, tetrahydrobiopterin. This cofactor is absolutely required for all aromatic amino acid hydroxylations, and, recently, nitric oxide production from L-arginine has also been found to be dependent on tetrahydrobiopterin. Phenylalanine hydroxylase catalyzes a coupled reaction in which phenylalanine is converted to tyrosine and in which tetrahydrobiopterin is converted to the unstable carbinolamine, 4a hydroxytetrahydrobiopterin. The enzyme, carbinolamine dehydratase, catalyzes the dehydration of the carbinolamine to quinonoid dihydropterin. A decreased rate of dehydration of this compound has been hypothesized to be responsible for the production of 7-biopterin found in certain mildly hyperphenylalaninemic individuals. We have now identified nonsense and missense mutations in the 4a carbinolamine dehydratase gene in a hyperphenylalaninemic child who excretes large amounts of 7-biopterin. This finding is consistent with the role of the carbinolamine dehydratase in the phenylalanine hydroxylation reaction. Together with previously identified inherited disorders in phenylalanine hydroxylase and dihydropteridine reductase, there are now identified mutations in the three enzymes involved in the phenylalanine hydroxylation system. In addition, the genetics of this system may have broader implications, since the product of the dehydratase gene has previously been shown to play an additional role (as dimerization cofactor for hepatocyte nuclear factor-1 alpha) in the regulation of transcription, through interaction with hepatocyte nuclear factor-1 alpha. PMID- 8352284 TI - Tay-Sachs genes in Acadians. PMID- 8352285 TI - The designation of mutations. PMID- 8352286 TI - Presymptomatic testing for Huntington disease in the United States. PMID- 8352287 TI - Fouling one's own nest revisited. AB - Transport of hazards from the workplace to the home by workers is a previously recognized but poorly addressed public health problem. Particularly disturbing are the childhood intoxications which may result from such paraoccupational exposure. Work clothes and shoes appear to be a common vehicle for hazard transport in recently reported cases as they were in the past, although other "markers" for potential paraoccupational exposure may be derived from case reviews. These include: poor workplace hygiene, occupational intoxications in adult workers, and the "cottage industry" phenomenon. These markers are reviewed in the context of recently reported cases and strategies are suggested to mitigate these easily preventable exposures. PMID- 8352288 TI - Survey of glycol ether use in Taiwan, 1991. AB - Glycol ethers (including glycol ether esters) are a group of solvents with medium high boiling points and low evaporation rates, possessing solvent characteristics of alcohol/ether functions (or ether/ester functions). They have been widely used in coatings and other industrial products for more than half a century. Recently, E-series glycol ethers have been found to show reproductive and teratogenic toxicity, and throughout much of the world they are being replaced by the so called P-series glycol ethers. In responding to the impact of the worldwide transition from E- to P-series glycol ethers, the current status of glycol ether use in Taiwan was studied. This study focuses on the type and quantity of these solvents being used, worker and public knowledge about their hazards, and possible changes in government regulations being considered. In this study, we found that large quantities of E-series glycol ethers were imported and used in Taiwan. The best estimates are: 2-ME, 2,500 tons; 2-EE, 1,200 tons; 2-EEA, 5,000 8,000 tons; 2-BE, 8,000 tons annually in 1991. For P-series glycol ethers, only about 2,500 tons are being used. Lack of knowledge about the potential toxic effects of the E-series glycol ethers is very common among users, regulatory agencies, academic institutes, and the general public. It is hoped that the results of this study, along with educational efforts, government regulations, and provision of technical services, will help prevent Taiwan from becoming a dumping site for these toxic chemicals. PMID- 8352289 TI - Evaluation of the national cancer program and proposed reforms. AB - A statement by some 68 prominent national experts in industrial medicine, carcinogenesis, epidemiology, and public health, released at a February 4, 1992 press conference in Washington, D.C., charged that the National Cancer Institute (NCI) has confused the public by repeated claims of winning the war against cancer. In fact, age standardized incidence rates have increased sharply over recent decades, while ability to treat and cure most cancers has not materially improved. Furthermore, the NCI has minimized evidence for increasing cancer rates which are largely attributed to smoking and to diet. In so doing, NCI trivializes the importance of occupational carcinogens as non-smoking-attributable causes of lung and other cancers, and ignores the tenuous and inconsistent evidence for the causal role of diet per se and also the important role of carcinogenic dietary contaminants. Reflecting this near exclusionary blame-the-victim theory of cancer causation, with support from the American Cancer Society and industry, the NCI discounts the role of avoidable involuntary exposures to industrial carcinogens in air, water, food, the home, and the workplace. The NCI has also failed to provide scientific guidance to Congress and regulatory agencies on fundamental principles of carcinogenesis and epidemiology, and on the critical need to reduce avoidable exposures to environmental and occupational carcinogens. Contrary to NCI, analysis of their $2 billion budget reveals very limited allocations for research on primary cancer prevention, and for occupational cancer which receives only $19 million annually, 1% of NCI's total budget. Problems of professional mindsets in NCI leadership--fixation on diagnosis, treatment, and basic research (much of questionable relevance) and the neglect of cancer prevention--are exemplified by the composition of the Executive President's Cancer Panel and the National Cancer Advisory Board. Contrary to the explicit mandate of the National Cancer Act, the Board is virtually devoid of recognized authorities in occupational and environmental carcinogenesis. These problems are further compounded by institutionalized conflicts of interest reflected in the composition of past Cancer Panels, and of the current Board of Overseers of the Memorial Sloan Kettering Cancer Center, NCI's prototype comprehensive cancer center, with their closely interlocking financial interests with the cancer drug and other industries. Comprehensive reforms of NCI policies and priorities are overdue. Implementation of such reforms is, however, unlikely in the absence of further support from industrial medicine professionals, which is here solicited, besides action by Congress and concerned citizen groups. PMID- 8352290 TI - Case-control study of congenital defects and parental employment in health care. AB - Health care workers may be occupationally exposed to known and suspected teratogens including viruses, anesthetic gases, sterilants, mercury, and x radiation. To assess the risk of congenital defects among offspring of health care workers, we analyzed parental occupational histories for 4,915 case babies with congenital defects, registered during the years 1968-1980 by the Metropolitan Atlanta Congenital Defects Program (MACDP) registry, and for 3,027 control babies born without defects during the same period. Offspring of mothers employed in a nursing occupation during the periconceptional period had a modest excess risk of having at least one congenital defect (relative risk [RR] = 1.42; 95% confidence interval [CI] 1.06-1.88); the offspring were at statistically significant increased risk of having anencephaly or spina bifida (RR = 2.00; 95% CI 1.01-4.30), coarctation of the aorta (RR = 2.06; 95% CI 1.10-3.82), genital system defects (RR = 1.61; 95% CI 1.03-2.53), and urinary system defects (RR = 3.43; 95% CI 1.41-8.34). These associations were not confounded by maternal age, education, or alcohol consumption. Offspring of mothers employed in administrative or clerical jobs in the health care industry also had a modest excess risk of defects (RR = 1.35; 95% CI 0.96-1.90), including a statistically significant excess risk of limb defects. We also found associations between neural tube defects and potential exposure to anesthetic gases and to x radiation, but each association was based on only three case babies of potentially exposed parents. We found no associations between defects and paternal health care employment, except for a few individual defects, and these were based on small numbers of exposed subjects. Only one of five previous studies reviewed found an increased risk of congenital defects among offspring of nurses, but three of the four negative studies had substantially smaller sample sizes than the present study. Detection bias may be a possible explanation for the apparent excess risk of certain defects among offspring of nurses. PMID- 8352291 TI - Health characteristics by longest held occupation and industry of employment: United States, 1980. AB - Occupational and industrial hazards are unevenly distributed in the workplace. National estimates for selected health indices of persons aged 17 years and over in the civilian noninstitutionalized population are presented for categories of longest held occupation and industry of employment. These estimates were based on data collected by the National Center for Health Statistics (NCHS) in the 1980 National Health Interview Survey (NHIS) and the Occupational Supplement, the first survey to collect data on longest held, in addition to current, occupation and industry of employment. Data on length of longest held job, limitation of activity, disability days, incidence of acute conditions, persons injured, hospitalizations, and utilization of medical and dental services are presented. PMID- 8352292 TI - Five-year follow-up study of hearing loss at several locations within a large automobile company. AB - This longitudinal epidemiologic study was designed to investigate hearing loss over a 5-year period among noise-exposed employees of a large automobile company and to assess effectiveness of hearing conservation programs at locations representing the spectrum of operations (assembly, light manufacturing, heavy manufacturing and machining, metal fabrication, and founding). Based on computerized audiometric test data, the study summarizes methodology developed for measuring occupational hearing loss and its application in evaluating programs at these locations, which had maximal 8-hr time-weighted average (TWA) noise exposures ranging from 104 to 110 dB(A). Methods presented here provide for consideration of age and hearing level of study subjects at baseline audiogram and clearly demonstrate the extent of hearing loss during the study period. Among five study locations, the average hearing loss at 2,000-4,000 Hz in the worst loss ear ranged from 3.4 to 6.2 dB over the follow-up period; after adjustment for presbycusis, the loss was less than 2 dB at all but one location, which showed a loss of nearly 4 dB. In comparison to a control group of nonnoise exposed employees, hearing conservation programs at four of the five locations were judged to be effective. One location, a metal fabrication plant with a large percentage of employees having an 8-hr TWA noise exposure over 90 dB(A), was particularly noted for the effectiveness of its program. PMID- 8352293 TI - Occupation and lung cancer risk among women in northern China. AB - Lifetime occupational histories were obtained in a case-control study of 965 female lung cancer patients and 959 controls selected from the general population in Shenyang and Harbin, People's Republic of China, where most women have worked outside the home. After adjusting for smoking, we found a significantly increased risk of lung cancer associated with employment involving the manufacture of transportation equipment (OR = 1.6, 95% CI = 1.0, 2.6), in particular the manufacturing of automobiles (OR = 3.0, 95% CI = 1.4, 6.4). Metal smelting and treatment workers were at an increased risk of lung cancer (OR = 1.5, 95% CI = 1.0, 2.1); the highest risks were observed among metal surfacers (OR = 3.1, 95% CI = 1.1, 9.0) and currently employed foundry workers (OR = 13.0, 95% CI = 1.7, 99.4). On the other hand, about a 50% decreased risk of lung cancer was observed among those employed in textile industries or as leaders of state and party organizations. Based on self-reports, exposures to coal dust and smoke from burning fuel at the workplace were also significant risk factors. The findings were similar when the analyses were confined to nonsmokers and were comparable across the major cell types of lung cancer. PMID- 8352294 TI - A health survey of workers in the pentachlorophenol section of a chemical manufacturing plant. AB - During 1968 to 1985, 109 workers who had been engaged in the production of pentachlorophenol, using non-gamma isomers of hexachloroclohexane (BHC) as the raw material, were surveyed. Endemic chloracne among them had been noted since 1974. The prevalence of chloracne was 73.4% (80/109) in total and 95.2% (20/21) in a trichlorobenzene (TCB) tank area where dioxin and dibenzofurans levels were thousands of ppm. To our knowledge, PCDDs and PCDFs have not previously been reported from thermal decomposition of BHC. Urinary porphyrins were significantly higher among exposed workers than among the controls but there was no significant difference between the workers with chloracne and those without. The conduction velocities of the median motor nerves were much slower among the workers in the TCB tank area where the highest PCDDs contamination appeared. The mortality study cohort was relatively young. Based on the three deaths observed during the follow up, no association could be drawn. PMID- 8352295 TI - Occupational risks for primary liver cancer in Shanghai, China. AB - Using occupational data for over 3,400 primary liver cancer cases diagnosed between 1980 and 1984 reported to the Shanghai Cancer Registry, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios were computed to generate leads to occupational risks of liver cancer. Among men, a statistically significant excess number of cases was observed for chemical processors, textile workers, wood workers, blacksmiths and machine-tool operators, and material handlers and dock workers. Increased incidence of liver cancer also was observed among female transport equipment operators. These findings indicate that a number of similar occupations are associated with increased risk of primary liver cancer in western countries and China. Although causal inferences cannot be drawn from these data, our study adds to the limited evidence of the potential role of occupational exposures in liver carcinogenesis. PMID- 8352296 TI - Resolution of an absolute scotoma and improvement of relative scotomata after successful macular hole surgery. AB - Visual loss in eyes with full-thickness macular holes is thought to be caused by the absence of retinal function in the area of the neurosensory defect as well as reduction in retinal function in the surrounding area of neurosensory retinal detachment. To improve characterization of the visual function of eyes after successful macular hole surgery, we studied six eyes preoperatively and postoperatively with macular microperimetry using the scanning laser ophthalmoscope. Best-corrected visual acuity was improved postoperatively in all eyes. Microperimetry performed preoperatively demonstrated an absolute scotoma that corresponded to the neurosensory defect in all eyes, with surrounding concentric isopters of relative scotomata. No detectable absolute scotoma was found in any eye postoperatively. All eyes showed partial or complete resolution of the surrounding relative scotomata. Improvements in visual acuity after successful macular hole surgery may be related to disappearance of a detectable absolute scotoma as well as improvement in the surrounding retinal function. PMID- 8352297 TI - Lipid exudation in age-related macular degeneration. AB - We reviewed the relationship between lipid exudation and subretinal neovascular membranes associated with age-related macular degeneration. The records of 500 consecutive patients with subretinal neovascular membranes caused by age-related macular degeneration were examined. Seventy-five patients (15%) (85 eyes) manifested lipid exudation in conjunction with subretinal neovascularization. Twelve patients (2.4%) (13 eyes) had a massive lipid exudative response with extensive serous retinal detachment (resembling Coats' disease). Of the 85 eyes with subretinal neovascular membranes and lipid exudation, 71 (84%) had a subretinal neovascular membrane that was classified as ill defined. Improvement of vision with or without treatment was seen in only 14 of these 85 eyes (16.4%). After comparing these 85 eyes to 94 eyes from 76 patients with age-related macular degeneration and subretinal neovascular membranes but no lipid exudation, we found that a subretinal neovascular membrane associated with lipid exudation was more likely to be ill defined (71 eyes [84%] vs 35 eyes [37%]; P = .0001), was more frequently associated with retinal pigment epithelial detachment (30 eyes [35%] vs 15 eyes [16%]; P = .0029), and was more likely not to have stabilization of visual acuity (14 eyes [16%] vs 31 eyes [33%]; P = .025). PMID- 8352298 TI - Pattern-reversal electroretinographic follow-up of laser photocoagulation for subfoveal neovascular lesions in age-related macular degeneration. AB - Pattern-reversal electroretinograms were used as an objective measure of macular integrity in a subset of 42 patients who were randomly assigned at enrollment in the Macular Photocoagulation Study to receive laser photocoagulation or no treatment for a subfoveal neovascular lesion. Pattern-reversal electroretinograms were obtained before randomization, three months and six months after randomization, and at six-month intervals randomization, and at six-month intervals thereafter. Responses were obtained to phase-alternating checkerboards of varying check size. Extrapolation of the best-fit regression line relating log check size to amplitude was used to determine retinal acuity. At each follow-up period, including three months after laser photocoagulation, treated eyes showed less loss in pattern-reversal electroretinographic acuity than untreated eyes. The decline in pattern-reversal electroretinographic acuity in untreated eyes corresponded to the rapid growth in the area of the subfoveal neovascular lesion. The more gradual decline in treated eyes was consistent with an increase in the area of the treatment scar caused by spreading atrophy. PMID- 8352299 TI - Clinical and immunologic features of human T-cell lymphotropic virus type I uveitis. AB - The clinical features of idiopathic uveitis were compared by the seropositivity for human T-cell lymphotropic virus type I. The statistical analysis of various clinical variables disclosed that the uveitis seen in seropositive patients (93 patients) had a significantly higher incidence of floaters, vitreous opacities, retinal vasculitis, and intermediate uveitis than that in seronegative patients (222 patients) (P < .05). The odds ratios of the virus infection for these clinical manifestations were high and statistically significant, suggesting that the virus infection has a role as a risk factor for the development of these clinical manifestations. Although visual acuity at the initial examination was almost equal between the two groups, after the therapy with topical or systemic corticosteroids, or both, visual acuity in seropositive patients was much better than that in seronegative patients. The surface phenotype of peripheral lymphocytes in the two groups was compared as follows: CD4-positive T lymphocytes (P < .05), CD4/8 ratio (P < .01), and CD25-positive T lymphocytes (P < .05) were significantly higher in seropositive patients than in seronegative patients. PMID- 8352300 TI - Subretinal neovascular membranes in Vogt-Koyanagi-Harada syndrome. AB - Subretinal neovascular membranes cause late visual loss and are important determinants of final visual acuity in patients with Vogt-Koyanagi-Harada syndrome. The purpose of this study was to determine the prevalence and risk factors associated with the development of subretinal neovascular membranes in Vogt-Koyanagi-Harada syndrome. We reviewed the charts of 58 patients (116 eyes) with Vogt-Koyanagi-Harada syndrome. We separated patients into two groups, one with and one without subretinal membranes. Demographic characteristics, namely age, gender, and race, initial and final visual acuities, duration and method of treatment, anterior chamber and vitreous cell, presence of fundus pigmentary disturbances, and phase of inflammation, were evaluated for each group. Overall, ten eyes (9%) of seven patients developed the subretinal neovascular membranes. Demographic characteristics among the two groups of patients were not markedly different (P > .10). Visual outcome of patients with subretinal membranes was significantly poorer than was that of patients without these membranes (P < .001). Eyes with subretinal membranes had a significantly greater degree of anterior chamber and vitreous inflammation (P < .02), greater incidence of fundus pigmentary disturbances (P < .02), and a greater frequency of chronic recurrent phase of inflammation, marked by recurrence of predominantly anterior chamber, and occasionally posterior segment, inflammation (P < .02). The membranes were located in the peripapillary (four eyes), subfoveal (three eyes), and macular extrafoveal (three eyes) regions. PMID- 8352301 TI - Choroidal nonperfusion in giant cell arteritis. AB - A 68-year-old man had visual loss secondary to isolated choroidal nonperfusion as a clinical manifestation of giant cell arteritis. Ophthalmoscopy disclosed scattered yellow-white lesions at the level of the retinal pigment epithelium in the posterior pole of the right eye. Intravenous fluorescein angiography demonstrated marked delay in choroidal filling of the macula in the right eye. There was no ophthalmoscopic or angiographic evidence of anterior ischemic optic neuropathy or central retinal artery occlusion. After approximately 72 hours of intravenous corticosteroid therapy, the patient's visual acuity improved and repeat intravenous fluorescein angiography showed normal choroidal circulation. Isolated choroidal ischemia is a potential cause of reversible visual loss in patients with giant cell arteritis. PMID- 8352302 TI - Factors associated with visual loss in patients with advanced glaucomatous changes in the optic nerve head. AB - We evaluated factors associated with decreased or stable visual function in 72 patients with primary open-angle glaucoma and complete cupping of the optic disk who were followed up five years or more. We found a significantly lower mean (15.4 +/- 2.7 mm Hg) and peak (24.5 +/- 6.9 mm Hg) intraocular pressure in those patients whose vision remained stable vs those whose vision decreased (21.3 +/- 3.2 and 39.2 +/- 11.0 mm Hg, respectively) (t-test, P < .001). Additionally, the variance of each patient's individual intraocular pressure readings measured during the follow-up period was lower in the group with stable vision (4.5 mm Hg) than in those in whom vision decreased (9.0 mm Hg) (F test, P < .001). Stepwise discriminant analysis disclosed that mean intraocular pressure, variance of an individual's intraocular pressure measurements over time, history of argon laser trabeculoplasty, and compliance with therapy discriminated 92.9% of patients (52 of 56) whose vision remained stable and 87.5% of patients (14 of 16) whose vision decreased. Reduction of intraocular pressure and compliance with therapy are important in patients with complete glaucomatous cupping of the optic disk. PMID- 8352303 TI - Lateral geniculate nucleus in glaucoma. AB - To assess glaucomatous damage to the lateral geniculate nucleus of the thalamus, as well as to its magnocellular and parvocellular layers, we examined the autopsy sections of the lateral geniculate nucleus of individuals with and without glaucoma. Five patients with a documented history of glaucoma and five controls with no ophthalmic or chronic central nervous system disease were included in this study. Neurons were counted in autopsy sections of the lateral geniculate nucleus. Cells were counted in 40 random microscopic fields of the magnocellular and parvocellular layers respectively. The mean magnocellular cell density for the glaucoma group of 2.72 +/- 0.13 cells per square millimeter (mean +/- SEM) was significantly less than that for the control group of 3.76 +/- 0.13 cells per square millimeter (P < .001). There was no statistical difference in the parvocellular layer. These data suggest that glaucoma leads to greater loss of magnocellular tissue at the level of the lateral geniculate. PMID- 8352304 TI - Aqueous tube-shunt implantation and pars plana vitrectomy in eyes with refractory glaucoma. AB - We reviewed the surgical outcome of 20 eyes of 20 consecutive patients who had undergone combined aqueous tube-shunt implantation and vitrectomy for complicated glaucoma associated with vitreoretinal disorders. After a mean follow-up of 10.39 +/- 5.43 months, visual acuity remained stable or improved in 13 patients (65%), and intraocular pressure was controlled (< 22 mm Hg) in 15 (75%). The most common complications were corneal edema (seven eyes) and choroidal effusion (three eyes). Combined tube-shunt implantation and pars plana vitrectomy may successfully control intraocular pressure and maintain preoperative visual acuity in refractory glaucoma associated with vitreoretinal disorders. PMID- 8352305 TI - The use of perfluorophenanthrene in the removal of intravitreal lens fragments. AB - We used perfluorophenanthrene as an aid during pars plana vitrectomy in removing lens fragments dislocated posteriorly into the vitreous cavity. We reviewed the records of all patients (nine patients, nine eyes) referred with dislocated lenses who underwent pars plana vitrectomy with perfluorophenanthrene for removal of the lens material at Wills Eye Hospital from July 1, 1991, through Nov. 30, 1991. The lens was dislocated during cataract extraction in eight eyes. One eye had a history of nonpenetrating trauma and lens dislocation. In one eye a retinal tear was noted intraoperatively and treated. Six eyes had postoperative visual acuity of 20/50 or better. In all eyes the lens was removed without further complications. Perfluorocarbon liquids such as perfluorophenanthrene may enhance current techniques by allowing easier and safer removal of displaced lens fragments through the pars plana. PMID- 8352306 TI - An adjustable double running suture technique for keratoplasty. AB - In a retrospective analysis, we examined 30 consecutive cases of penetrating keratoplasty in which a double running 10-0/11-0 nylon suture technique was used and the 10-0 suture was adjusted early in the postoperative period to reduce astigmatism. When the response to suture adjustment was inadequate, the presence of the 11-0 suture allowed for early (ten to 18 weeks) removal of the 10-0 suture. Rapid visual recovery (12.3 +/- 0.95 weeks; mean +/- standard error) and low levels of final astigmatism (2.66 +/- 0.24 diopters) were achieved. Visual acuity was 20/20 to 20/40 in 25 of the 28 patients (89%) who were visually rehabilitated. In these 28 patients, visual acuity remained stable for the remainder of the study. All patients had a minimum of six months' follow-up from the time of surgery; mean follow-up was 10.6 +/- 1.70 months. PMID- 8352307 TI - Visual improvement as a function of time after lamellar keratoplasty for keratoconus. AB - Twenty-eight keratoconic patients with either contact-lens intolerance or marked corneal scarring over the visual axis underwent lamellar keratoplasty for visual rehabilitation. All 28 patients returned for follow-up at six months, 27 (98%) had follow-up at one year, and 23 (82%) at two years. The 23 patients with two year follow-up showed progressive improvement of visual acuity over time. At six months, 11 of 23 patients (48%) had visual acuity of 20/30 or better. At one year, 17 of 23 (74%) had 20/30 or better, and at two years, 21 of 23 (91%) had 20/30 or better. The average postoperative keratometry measurement at two years was 43.5 diopters (S.D. = 2.5 diopters), which represented an average reduction of 13 diopters from preoperative keratometry. All patients who were less than 32 years old obtained visual acuity of 20/30 or better after two years and reached this level significantly (F = 6.75, P = .02) sooner than those more than 32 years old. These results compare favorably with previously reported visual results after penetrating keratoplasty. PMID- 8352308 TI - Medial canthotomy and cantholysis in eyelid reconstruction. AB - Combined medial canthotomy and cantholysis is a quick, technically simple, single stage reconstructive technique for use in the reconstruction of the upper or lower eyelid. This technique, which transects one lacrimal canaliculus, provides up to 20% of the horizontal eyelid dimension for closure. Medial canthotomy and cantholysis is most frequently used in combination with other eyelid reconstructive techniques for difficult reconstructions, which would otherwise require more extensive surgical procedures. The surgical technique is readily performed with the patient under general anesthesia and entails the transection of one lacrimal canaliculus, lysis of one crus of the medial canthal tendon, and lateral advancement of the medial eyelid stump. We used medial canthotomy and cantholysis in the reconstruction of 29 eyelid defects (21 upper eyelids and eight lower eyelids) over a 12-year period with adequate reconstructive results in all cases. Eleven of the patients underwent simultaneous lateral canthotomy and cantholysis. Complications of the medial canthotomy and cantholysis technique include anterior displacement of the medial portion of the eyelid, epiphora, notching of the medial portion of the eyelid, medial ectropion, and blepharoptosis. If used with appropriate case selection, this technique allows an optimal reconstructive result to be achieved with a minimum of operative time and morbidity. PMID- 8352309 TI - The effect of anterior transposition of the inferior oblique muscle. AB - The effect of anterior transposition of the insertion of the inferior oblique muscle was compared with the results from conventional inferior oblique muscle recession in 50 patients. Even though both groups of patients had a similar degree of overaction preoperatively, postoperative inferior oblique muscle action was weaker (P < .01) and upgaze more limited P < .01) in the anterior transposition group. These data suggest that anterior transposition serves to convert the inferior oblique muscle from an elevator to a depressor on attempted elevation. Because anterior transposition is such a powerful weakening operation, we suggest that it be reserved for patients with moderate to severe inferior oblique muscle overaction. To avoid postoperative hypotropia in upgaze, anterior transposition should be performed in both eyes for bilateral inferior oblique muscle overaction and not unilaterally. PMID- 8352311 TI - Vitrectomy surgery for full-thickness macular holes. PMID- 8352310 TI - Congenital cysts of the iris stroma. AB - We managed three cases of congenital iris stromal cysts and compared them with 22 cases in the published reports to delineate the clinical features of this condition and determine the best treatment. Our first patient, a 5-month-old girl, had injection of a cyst with trichloroacetic acid, but developed a cataract and endothelial damage to the cornea and the eye was eventually enucleated. Our second patient, a 9-week-old girl, was treated with repeated xenon photocoagulation, drainage of the cyst, and cryotherapy, but required enucleation of the eye. Our third patient, a 5-month-old girl, had excision of the cyst by sector iridectomy with preservation of vision and no recurrence two years later. Our results suggest that complete surgical excision is a superior method of treatment for congenital cysts of the iris stroma. PMID- 8352312 TI - Corneal edema after miochol. PMID- 8352313 TI - Specular microscopy and fluorophotometry in the diagnosis of epithelial downgrowth after a sutureless cataract operation. PMID- 8352314 TI - Blink-associated eye movements with contact-lens wear. PMID- 8352315 TI - Corneal ulcer caused by combined intravenous and anesthetic abuse of cocaine. PMID- 8352316 TI - Basal cell carcinoma of the conjunctiva. PMID- 8352317 TI - Varix of the angular vein manifesting as a medial canthal mass. PMID- 8352319 TI - Retinal hemorrhages as an early sign of acute bacterial endophthalmitis. PMID- 8352318 TI - Monozygotic twin sisters with adult vitelliform macular dystrophy. PMID- 8352320 TI - Ocular coccidioidomycosis. PMID- 8352321 TI - Lens clarity after vitrectomy in traumatic lens perforation and vitreous penetration. PMID- 8352322 TI - 25-gauge intraocular forceps. PMID- 8352323 TI - Chiasmal compression from fat packing after transsphenoidal resection of intrasellar tumor in two patients. PMID- 8352324 TI - The efficacy of optic nerve sheath decompression for anterior ischemic optic neuropathy and other optic neuropathies. PMID- 8352325 TI - Clinical follow-up of phototherapeutic keratectomy for treatment of corneal opacities. PMID- 8352326 TI - Therapeutic use of humor in occupational therapy. AB - Interviews with five occupational therapists who use humor therapeutically in their practice were conducted and analyzed with a phenomenological method so that the lived experience of therapeutic humor use in occupational therapy could be examined. Sixteen themes were identified through data analysis: The Concept of Therapeutic Use of Humor; Spontaneous Versus Deliberate Humor; Humor, the Great Equalizer; Humor and Professionalism; Contraindications of Humor; Humor Among Co Workers; Humor and Play; Humor and the Environment; Humor Providing Balance; The Intrinsic Quality of Humor; The Transformative Power of Humor; The Effects of Humor on the Subjects Themselves; Humor as an Evaluation and Treatment Tool; Humor as Therapeutic Use of Self; Humor as a Coping Mechanism; and Other Uses of Humor With Patients. This study revealed that the use of therapeutic humor in occupational therapy is a multifaceted phenomenon, much richer than had been previously presented in the literature. PMID- 8352328 TI - Combining practice and research. AB - Although many authors advocate research involvement for occupational therapists involved in clinical practice, no formal studies existed of the personal, educational, and workplace environmental factors though to affect therapists' ability to integrate clinical research with practice. This exploratory, descriptive study surveyed 103 occupational therapists reporting work functions of both direct patient care and research. Major findings included: (a) workplace learning circumstances focusing on performance and application of clinical research were important for adopting a dual practice-research role, (b) research activities reflected the evolving character of the role, (c) administrative support and a personal commitment to research were critical for success, and (d) formal research courses were important, but so were informal discussions regarding application and problem solving. The findings have implications for university curricula, continuing education, and clinical environments. PMID- 8352327 TI - Age differences in functional performance. AB - We compared the functional performance of 20 young adult women and 20 older adult women on two types of tasks. One type of task was normal instrumental activities of daily living (e.g., meal preparation, home maintenance) that were meaningful, familiar, and well practiced. The other type was a contrived, relatively unfamiliar task of wrapping a package. Although young and old women did not differ significantly in their familiarity with the two tasks, results from two repeated measures MANOVAs revealed a significant age difference in both activities. This finding suggests that older adults show age-related decline with tasks even when those tasks are familiar, practiced, and ecologically valid. PMID- 8352329 TI - Improvement in upper extremity function and trunk control after selective posterior rhizotomy. AB - Selective posterior rhizotomy is being increasingly used in the treatment of spasticity associated with cerebral palsy. Anecdotal reports in the literature note that this procedure results in improved upper extremity function and trunk control. We present a systematic analysis of the results of selective posterior rhizotomy performed on patients with cerebral palsy at Santa Rosa Children's Hospital. Patients were video-taped before surgery and one year postoperatively. These videos were reviewed blind by an occupational therapist who graded patients' performance on three tasks: assumption of side sitting, maintenance of side sitting, and block building. Statistically significant improvements were noted in all three categories with p values of .0003, .0001, and .0044 respectively. These results support the anecdotal reports of improvement in upper extremity function and trunk control with selective posterior rhizotomy. PMID- 8352330 TI - Attending behavior: a descriptive study of children aged 18 through 23 months. AB - The purpose of this study was to provide descriptive data on the attending behavior of children aged 18 through 23 months. The method used was designed to be clinically feasible for occupational therapy practitioners. Forty-eight children between the ages of 18 and 24 months were studied through observation of a 15-min session of free play with a standard set of toys. The child's physical contact with objects was used as a guideline for timing. Four factors were examined: total time attending, total number of activities attended to, average attending time per activity, and longest time attending to one activity. The Mann Whitney U statistic revealed that there were no significant differences between boys and girls on any of the four factors. There were, however, statistically significant differences between children aged 18 through 20 months and children aged 21 through 23 months for all of the factors except longest time attending to one activity. The children in this study changed activities frequently (median of 10 activities in 15 min) and attended briefly (median attending time per activity of 81 sec). They were, however, capable of attending to one activity for much longer periods of time (median of 225 sec). With minimal adult intervention, the children spent an average of 12.5 min attending to the toys during a 15-min session. These results may augment other aspects of occupational therapy assessment by offering some insight into whether or not an individual child demonstrates age-appropriate attending behavior. Additionally, this standardized method of observation may offer occupational therapists a clinically feasible means of assessing attending behavior. PMID- 8352331 TI - Death in very old age: a personal journey of caregiving. AB - This paper describes a personal journey of caregiving for a very old family member during dying and death. The phenomenology of caregiving reveals the inner struggle experienced by all caregivers, lay and professional, between the needs to support both the living and the dying of the terminally ill person. The lived experience unfolds in phases of caregiving that support a stage theory of development in professionals' work with dying persons. The concept of presencing or connecting is a vital component of terminal care and has implications for occupational therapy practice. Occupational therapists can use their knowledge and understanding of occupation to bring about connecting in the dying experience. The contributions of all participants in the dying experience--family caregivers, the dying person, and health professionals--are important as sources of mutual support in the work of dying. PMID- 8352332 TI - An international overview of resource centers on disability. AB - Facilities variously known as independent living centers, disabled living centers, disability information centers, and resource centers now exist in many parts of the world. Although occupational therapists offer valuable perspectives on quality of life, knowledge of assistive technology, and a holistic view of clients' needs, occupational therapy is not always a part of these centers. Occupational therapists themselves may overlook these settings as venues for their services. This overview of 38 resource center organizations in 14 countries reports on their approaches to supporting persons with disabilities, professionals, and other members of the public and explores the presence of occupational therapy and other professions in these agencies. PMID- 8352333 TI - A comparison of practice issues among occupational therapists in the rural Northwest and the Rocky Mountain regions. AB - The purpose of this study was to investigate factors that affected occupational therapy practice in the rural regions of the Rocky Mountains. It compared data from the Rocky Mountain region (Wyoming, Colorado, New Mexico, Utah, and Arizona) to a previous study of the Northwest region of Alaska, Idaho, Montana, and Washington and expanded on the Northwest study. Results indicated that the two areas were similar in their demographics and problems, including need for more occupational therapists. The results also have implications regarding specialized preservice training for rural-based occupational therapists, other professions' availability of continuing education, and other support systems. The authors provide recommendations based on the results, other literature, and conjectures, for recruitment, training, and ongoing support of rural occupational therapists through cooperative consortiums and distance learning. PMID- 8352334 TI - Electrical stimulation for restoring independent feeding in a man with quadriplegia. PMID- 8352336 TI - Partition of occupational science and occupational therapy: sorting out some issues. PMID- 8352335 TI - Graded activity: legacy of the sanatorium. AB - Occupational therapists in all areas of practice grade therapeutic activities to help patients progress toward their goals. It is proposed in this paper that the concept of graded activity originated in German tuberculosis sanatoria in the late 1800s, when patients were required to walk on graded (sloped) land for exercise. British physician Marcus Paterson included work, as well as walking, in his graduated exercise program for tuberculosis patients and was honored for this innovation at the founding meeting of the National Society for the Promotion of Occupational Therapy (NSPOT). George Barton, Susan Tracy, and Herbert Hall were among the NSPOT members who contributed to the development of graded activity as a principle in occupational therapy intervention. The military rehabilitation programs established during World War I provided additional impetus, and by the mid-1920s, graded activity was recognized as central to the profession. PMID- 8352337 TI - Journal articles are inappropriate for special group interests. PMID- 8352338 TI - Patient care for the twenty-first century: asserting professional values within economic restraints. PMID- 8352339 TI - Joseph T. English, M.D., one hundred twenty-first president, 1992-1993. PMID- 8352340 TI - A new beginning II. PMID- 8352341 TI - Ethics, empathy, and gender in health care. AB - The changes that have taken place in medicine over the past few decades have challenged our views about the responsibilities and obligations of those providing health care and about their relationships with their patients. The demands brought by technologic advances and economic concerns have tested our ability to practice humane, empathic, and ethical medicine. This paper addresses the connection between ethics and empathy in the context of our current health care system. The author reviews the concept of empathy and argues that ethical medicine is empathic medicine. Since gender differences in health care needs and disparities in treatment have been identified, gender serves to focus some of the issues and exemplify some concerns about empathic and ethical practice. PMID- 8352342 TI - Intergenerational transmission of child abuse: rates, research, and clinical implications. AB - OBJECTIVE: The author reviews current wisdom concerning the rates and mechanisms of intrafamilial components of intergenerational transmission of child abuse and illustrates the unreliability of basic data and of assumptions made by reviewers and partisan advocates, most of whom underestimate the importance of intrafamilial factors in child abuse. METHOD: The information in the report was derived from original research plus a recently prepared compilation of 60 studies, mainly from the United States and the United Kingdom. RESULTS: The crude rates of intergenerational transmission of child abuse according to the studies reviewed are as follows: one-third of child victims grow up to continue a pattern of seriously inept, neglectful, or abusive rearing as parents. One-third do not. The other one-third remain vulnerable to the effects of social stress on the likelihood of their becoming abusive parents. Intrafamilial factors appear to be the cause of personally directed, as opposed to culturally condoned, child abuse. Broad social factors, and some medical and psychiatric conditions, lower or raise thresholds in which family and personal vulnerabilities and propensities operate. CONCLUSIONS: There is no justification for any extremist advocacy in apportioning responsibility between the "sins of the parents" and the failings of society. The contention that clinical research on abuse is inferior to, and must give way to, large-scale or statistically balanced self-report and questionnaire surveys is plausible, popular, convincing, and wrong. PMID- 8352343 TI - Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients. AB - OBJECTIVE: The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in schizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its main symptoms. METHOD: Seventy male schizophrenic patients underwent [18F]-fluorodeoxyglucose positron emission tomography after a period of at least 4 weeks during which they had not received neuroleptic medication and were compared to 30 age-matched male normal comparison subjects. RESULTS: Analyses revealed decreased metabolism in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ventral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previous studies, the schizophrenic group had lower hypofrontality scores (ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic patients did not differ from that of comparison subjects, while occipital cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal activity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for each schizophrenic patient on the scan day, were correlated with regional brain glucose metabolic rate. Medial frontal cortical and thalamic activity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and hypofrontality scores did not significantly correlate with negative symptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions. CONCLUSIONS: Low metabolic rates were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striatal-thalamic pathways in schizophrenia. Loss of normal lateralization patterns was also observed on an exploratory basis. Correlations with negative symptoms and group differences were more prominent in medial than lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology. PMID- 8352344 TI - Parkinsonism in neuroleptic-naive schizophrenic patients. AB - OBJECTIVE: Previous studies in schizophrenia have identified abnormalities involving the basal ganglia, but the contribution of neuroleptics to the motor system abnormalities in schizophrenia is usually a confounding factor. This study addressed the issue of whether parkinsonism, a reflection of dopaminergic hypofunction, occurs in schizophrenia per se. METHOD: Clinical ratings and quantitative instrumental measures of parkinsonian rigidity, tremor, and bradykinesia were obtained in 24 neuroleptic-naive schizophrenic patients and 24 age- and gender-matched comparison subjects. RESULTS: According to the clinical ratings, 21% of the schizophrenic patients had rigidity and 12% had bradykinesia, in contrast to none of the normal comparison subjects. With the use of instrumental measures, rigidity and tremor were observed in 29% and 37%, respectively, of the schizophrenic patients, compared to 4% and none in the normal comparison group. The schizophrenic patients also exhibited greater right side than left-side parkinsonism. CONCLUSIONS: The findings suggest that extrapyramidal motor signs may be part of schizophrenia proper and that some patients with schizophrenia have left striatal hypodopaminergia unrelated to neuroleptic treatment. PMID- 8352345 TI - Establishing the onset of psychotic illness. AB - OBJECTIVE: To date, the literature has provided no standardized, replicable method for establishing illness onset. The authors describe a method for dating the first appearance of prodromal signs of psychotic illness, the emergence of an acute episode, and the initiation of treatment seeking. METHOD: Using reports by family and friends about a sample of 141 subjects with first-episode psychosis, the investigators derived a checklist of behaviors describing the evolution of various phases of illness. Supplied with the checklist, clinician pairs independently rated the critical phases in the evolution of illness: first appearance of noticeable symptoms, first appearance of prominent psychotic symptoms, and initiation of treatment seeking. RESULTS: The judges achieved good reliability in assigning age at the first appearance of psychotic symptoms and at initiation of treatment seeking. Judging the beginning of the prodrome proved more difficult. Insidious onset proved as characteristic of affective psychosis as of schizophrenia, while treatment lag--the interval between emergence of acute psychotic symptoms and initiation of treatment seeking--was longer for schizophrenia than for affective psychosis. Onset of schizophrenia occurred earlier in women than in men. Depression with psychotic features appeared earlier in men than women. CONCLUSIONS: Although dating the onset of illness phases is probably feasible, efforts to improve reliability must continue. The study results challenge beliefs about gender differences in age at onset. PMID- 8352346 TI - Contrasts between patients with affective disorders and patients with schizophrenia on a neuropsychological test battery. AB - OBJECTIVE: This study was designed to ascertain the degree and specificity of cognitive impairments in patients with schizophrenia and patients with affective disorders. METHOD: Cognitive function was assessed with a neuropsychological test battery in consecutively admitted patients with schizophrenia (N = 57), unipolar depression (N = 29), and bipolar disorder (N = 16). RESULTS: The performance of the schizophrenic group was significantly below that of the groups with affective disorders on measures of attention and psychomotor speed, verbal and visual memory, and problem solving and abstraction. IQ was lower in the schizophrenic group and appeared to have deteriorated from a normal premorbid level that was not different from that of the affective disorder groups, as determined by the Wide Range Achievement Test--Revised reading test, a putative measure of premorbid intelligence. When IQ was controlled, differences between the groups in problem solving and visual memory remained. Psychiatric symptoms had a larger impact on test performance in the affective disorder groups than in the schizophrenic group. CONCLUSIONS: These results suggest that patients with schizophrenia perform systematically worse on cognitive measures than patients with affective disorders, which is consistent with their generally poorer outcome. The results also indicate that schizophrenia and affective disorders are qualitatively distinguishable in neuropsychological terms, given differences in apparent intellectual deterioration, profiles of cognitive impairment, and associations between cognitive performance and psychopathology. PMID- 8352347 TI - A comparative study of paranoid and schizoid personality disorders. AB - OBJECTIVE: Family studies have demonstrated a higher rate of schizoid personality in the families of probands with schizophrenia and a higher rate of paranoid personality in the families of probands with delusional disorder. The authors sought to investigate the familial characteristics of probands with schizoid and paranoid personality disorders and to delineate the clinical characteristics of the two groups. METHOD: Records of 351 inpatients with discharge diagnoses that included the term "schizoid personality" or "paranoid personality" were examined to identify patients who met DSM-III-R criteria for schizoid personality disorder (N = 34) or paranoid personality disorder (N = 19). Comparisons were made between the two groups with respect to clinical symptoms, familial characteristics, and longitudinal course. RESULTS: The authors found that probands with schizoid personality disorder were hospitalized at an earlier age than probands with paranoid personality disorder, had more intervention before the index admission, and had greater morbidity following the index admission. They also found that descriptors of the two syndromes tended to congregate in the respective family material, but the differences were not statistically significant. Differences in the familial prevalence of schizophrenia were also not statistically significant. CONCLUSIONS: These familial data do not support the hypothesis that schizophrenia congregates in the families of probands with schizoid personality disorder. Possible explanations for this finding are discussed. PMID- 8352348 TI - Profiles and predictors of assaultiveness for different psychiatric ward populations. AB - OBJECTIVE: The authors examined associations between patient-related characteristics and assaultiveness on six different psychiatric wards to determine 1) the relative contributions of demographic, disorder-related, and diagnostic variables to prediction of assaultiveness and 2) how ward composition and type of victim affect prediction of assaultiveness. METHOD: Hospital records of 1,025 inpatients residing in psychiatric wards within a 6-month time frame were reviewed for evidence of assaultiveness. Data on all 260 assaultive patients and a sample of 136 of the nonassaultive patients were analyzed with multiple regression to predict assaultiveness scores for each ward and each victim category. RESULTS: The findings indicated high rates of assaultive patients and assaults on fellow patients. Multiple regression results produced different predictors of assaultiveness for different wards but not for different categories of assault victim within each ward. Overall, age and sex consistently failed to predict assaultiveness, whereas greater assaultiveness was significantly associated with a greater proportion of time hospitalized since first admission. The most powerful unique predictors of assaultiveness scores were diagnostic distinctions derived from data on coexistent diagnoses. The most assaults were by acute patients whose diagnoses excluded organic mental disorder but included either bipolar disorder or personality disorder and longer-stay patients whose exclusive diagnosis was organic mental disorder. CONCLUSIONS: This identification, albeit modest, of risk factors for assaultiveness on different wards nevertheless provides information fundamental to the management policies of psychiatric institutions. The findings caution against aggregating different ward populations for research on assaultiveness and endorse the usefulness of coexistent diagnoses for predicting assaultiveness. PMID- 8352349 TI - Short-term clinical prediction of assaultive behavior: artifacts of research methods. AB - OBJECTIVE: The apparent accuracy of predictions of assaultive behavior in psychiatric inpatients varies substantially, depending on the method used to study the prediction. The authors explored the effects of different measures and sampling strategies on short-term clinical predictions of dangerousness. METHOD: The index subjects were patients who were rated by intake clinicians as potentially highly assaultive on the ward (N = 32) and patients who were involuntarily committed on grounds of danger to others (N = 32). The respective comparison groups comprised patients predicted by clinicians not to be assaultive (N = 32) and patients committed for reasons other than danger to others (N = 40). The text of unit meetings and data from chart reviews were used to determine the occurrence and dates of violent acts, seclusions for violent acts or threats, and violent threats. RESULTS: There was a significant difference in the rate of inpatient violence between the subjects rated at admission as potentially assaultive (75.0%) and patients rated as not potentially assaultive (12.5%), but the difference in the rates of violence between the patients who were (56.0%) and were not (42.0%) involuntarily committed as dangerous to others was not significant. Most of the violent acts occurred relatively late in the hospitalization, but seclusions occurred almost exclusively in the initial stages of hospitalization. CONCLUSIONS: The reported accuracy of clinical predictions of assaultive behavior is markedly affected by the choice of sampling strategy, comparison group, outcome measures, and follow-up period. Including seclusion and violent threats in the outcome variable appears to lead to deceptive findings. PMID- 8352350 TI - Seasonality in violent suicide but not in nonviolent suicide or homicide. AB - OBJECTIVE: Previous studies have reported seasonal or monthly variation in suicide. The present study was conducted in order to determine seasonality and other significant rhythms in violent and nonviolent suicide, alone and together, and homicide. METHOD: Data on suicide, violent suicide, nonviolent suicide, and homicide (categorized according to ICD-9) for all of Belgium for the period 1979 1987 were analyzed by means of spectral analyses. RESULTS: There was a significant seasonality for suicide but not homicide. Seasonality was present in violent but not in nonviolent suicide. The number of violent suicides increased with age and was more prominent in men. The violent suicide chronograms of younger and elderly persons were quite distinct in the occurrence of peaks in March-April and August, respectively, and lows in December-January. There was no significant relationship between violent suicide and homicide. CONCLUSIONS: Seasonality in suicide is determined by significant circannual rhythms in violent suicides, which differ between younger and elderly persons. PMID- 8352352 TI - Beginning careers in academic psychiatry for women--"Bermuda Triangle"? AB - OBJECTIVE: The proportion of women in leadership positions in academic psychiatry has not kept pace with the increase in the number of women entering the field. This study examines differences in career activities between women and men who graduated from the Yale University psychiatric residency training program and explores whether these differences can be explained by preresidency expectations, residency experiences, or training immediately after residency. METHOD: Departmental educational records of the Yale residency program were reviewed to determine professional interests expressed before psychiatric residency and training focus during residency for 355 residents in the 1970-1983 graduating classes. A 1984 follow-up study focused on their postresidency career activities. Differences in preresidency interests and experiences, training activities, and career paths between all female and male graduates and between women and men who chose academic careers were examined. RESULTS: After residency, the female graduates' marital status differed from men's--more had never married or were divorced. Women's professional activities diverged from men's; their practice pattern was different, they spent more hours teaching, and they had fewer publications in peer-reviewed journals. This divergence was not accounted for by differences in pretraining interests or in training focus during residency. The authors present possible explanations. CONCLUSIONS: Further research is indicated to determine the underlying causes of career differences between women and men in psychiatric practice and academia so that effective strategies for correcting the present inequality of women in senior faculty positions can be implemented. PMID- 8352351 TI - The abnormality of normal comparison groups: the identification of psychosis proneness and substance abuse in putatively normal research subjects. AB - OBJECTIVE: Careful assessment of research subjects is important because the inclusion of subjects who manifest psychopathology and significant substance abuse in normal comparison groups will decrease statistical and experimental power. The current study evaluated the usefulness of an MMPI-derived algorithm in identifying tendencies toward psychosis and substance abuse in putatively normal research volunteers. METHOD: Ninety-eight adults who were recruited as normal comparison research subjects completed the MMPI, psychiatric interviews, questionnaires, and selected neuropsychological tests. The MMPI classified 81 presumed normal subjects into four subgroups: 1) not psychosis prone/substance abuse not likely, 2) not psychosis prone/substance abuse likely, 3) psychosis prone/substance abuse not likely, and 4) psychosis prone/substance abuse likely. RESULTS: The MMPI psychosis-prone and substance abuse factors identified significantly distressed and dysfunctional individuals with a relatively high degree of accuracy. CONCLUSIONS: It is becoming increasingly apparent that the cursory self-report screening of normal subjects may result in unacceptable levels of psychopathology in comparison groups. The current results also indicate that an adequate substance abuse evaluation is extremely important and that brief self-report information may be misleading. Empirically derived assessment tools, such as the MMPI, may prove useful in allowing researchers to more accurately define control parameters and group membership. PMID- 8352353 TI - Familial aggregation of emotional and behavioral problems of childhood in the general population. AB - OBJECTIVE: This study sought to evaluate the existence and implications of familial aggregation of emotional and behavioral problems of childhood in a general population sample. METHOD: The children included in the study were chosen with the use of a sampling technique that identified households in which there were two or more children aged 4-16 years living at home at the time of the survey. Ratings on checklists of emotional and behavioral problems were obtained from parents, teachers of children in elementary school, and the children themselves if they were adolescents aged 12-16. Children were classified as having problems if their scores on scales of conduct, attention deficit, or emotional problems were in the top 10% of the distribution of scores from any informant. RESULTS: There was evidence for familial aggregation of these problems, particularly conduct and emotional problems. However, this was largely derived from the parents' reports of symptoms, not the teachers' or adolescents' reports. The degree of familial aggregation varied according to certain sibship characteristics and patterns of comorbidity. CONCLUSIONS: Familial aggregation of emotional and behavioral problems does exist in a community population and is not simply an artifact of clinic attendance. PMID- 8352354 TI - Smooth pursuit eye movements and saccadic eye movements in patients with delusional disorder. AB - OBJECTIVE: This study used eye movement tests to examine whether frontal lobe dysfunction is present in delusional disorder. METHOD: Smooth pursuit and voluntary saccadic eye movements of 15 delusional patients, 40 schizophrenic patients, and 40 normal subjects were recorded and analyzed statistically. RESULTS: The schizophrenic patients differed significantly from the normal subjects in some smooth pursuit eye movement characteristics, whereas both the schizophrenic and the delusional patients showed more saccades than the normal subjects during the smooth pursuit test. The delusional patients and normal subjects differed significantly in some voluntary saccadic eye movement characteristics. CONCLUSIONS: The data support the idea of a biological dysfunction in eye tracking in delusional disorder. PMID- 8352355 TI - Prediction of response to haloperidol dose reduction by Span of Apprehension measures for treatment-refractory schizophrenic patients. AB - Thirteen treatment-refractory schizophrenic patients participated in a haloperidol reduction study. Two of the subjects were unable to tolerate medication reduction. These subjects were comparable to the other patients in terms of initial clinical variables but were outliers on baseline accuracy and reaction time measures from the Span of Apprehension. The results suggest that aspects of basic visual processing and motor response speed may identify patients who require higher neuroleptic doses. PMID- 8352356 TI - Light therapy of late luteal phase dysphoric disorder: an extended study. AB - Nineteen patients with late luteal phase dysphoric disorder (LLPDD) and 11 healthy comparison subjects underwent a 3-month crossover trial of bright (more than 2500 lux) white morning, bright white evening, and placebo dim (less than 10 lux) red evening light, administered daily for 1 week during the premenstrual phase of the menstrual cycle. All light treatments significantly reduced depressive ratings from baseline levels. PMID- 8352357 TI - Need to clarify DSM-III-R depersonalization disorder. PMID- 8352358 TI - Paradoxical sedation with sertraline. PMID- 8352359 TI - Ephedrine arousal. PMID- 8352361 TI - Captopril-induced mania. PMID- 8352360 TI - Unrecognized pregnancy during citalopram treatment. PMID- 8352362 TI - Treatment of flashbacks with naltrexone. PMID- 8352363 TI - Influence of clozapine on water dysregulation. PMID- 8352364 TI - Arnold Bennett, Clayhanger, and Alzheimer's disease. PMID- 8352365 TI - Rates of schizophrenia among males and females. PMID- 8352367 TI - Cost containment and the profit motive. PMID- 8352366 TI - Role of DHEA and DHEA-S in Alzheimer's disease. PMID- 8352368 TI - Clozapine, obsessive symptoms, and serotonergic mechanisms. PMID- 8352369 TI - Clozapine, obsessive symptoms, and serotonergic mechanisms. PMID- 8352370 TI - The file drawer problem in the meta-analysis of the subjective responses to alcohol. PMID- 8352371 TI - Assessment of onset of panic disorder in relation to onset of agoraphobia. PMID- 8352372 TI - Effect of topical 5-aminosalicylic acid (5-ASA) therapy on rectal mucosal biopsy morphology in chronic ulcerative colitis. AB - Classic teaching emphasizes that chronic ulcerative colitis is characterized morphologically by the presence of fixed architectural and cellular mucosal changes that categorize the process as chronic. To examine the effect of topical 5-aminosalicylic acid (5-ASA) enemas on the presence of six histological features of chronicity in established chronic ulcerative colitis, 123 mucosal biopsies were taken prospectively at 1-month intervals, all from the same anatomic location (10 cm), from 14 patients treated with either 5-ASA or placebo enemas. The biopsies were evaluated for the presence of mixed inflammation in the lamina propria, crypt architectural abnormalities, basally located lymphoid aggregates, basal plasmacytosis, villiform surface epithelial configuration, and Paneth cell metaplasia. Overall, 29% of biopsies from 64% of patients were histologically normal (no chronic features, no active disease). Compared with patients treated with placebo enemas, patients treated with 5-ASA enemas showed a significantly higher percentage of normal biopsies (36% ASA group vs. 12% placebo group; p = 0.005) and a lower percentage occurrence of each individual histological feature of chronicity. In addition, patients treated with 5-ASA had a higher average number of normal biopsies per patient (3.0) than those treated with placebo enemas (1.3). Therefore, histologically normal-appearing mucosal biopsies do occur in established cases of chronic ulcerative colitis, and this finding is enhanced by treatment with 5-ASA enemas. Awareness of these results should prevent the presence of normal rectal mucosal biopsy findings in chronic ulcerative colitis patients from being misinterpreted as either evidence against this diagnosis or as representing focal skip areas characteristic of Crohn's disease. PMID- 8352373 TI - Adiaspiromycosis: an unusual fungal infection of the lung. Report of 11 cases. AB - Adiaspiromycosis (ad"i-ah-spi"ro-mi-kosis) is a worldwide, noninfectious, nonarthropod transmitted fungal infection of lower vertebrates, most commonly rodents. Humans become an accidental host by inhaling dust-borne spores (conidia) of the saprophytic soil fungus, Emmonsia crescens (recently renamed Chrysosporium parvum variety crescens). We report 11 cases of this unusual deep mycosis from South America, Europe, and the United States. The severity of the disease depends on the number of spores inhaled. In limited inoculum, the disease remains localized (two cases), whereas in heavy inocula the fungus involves both lungs (nine cases) and presents as a diffuse reticulonodular infiltrate. In this disseminated form, patients usually complain of cough, dyspnea on exertion, and low-grade fever mimicking other systemic fungal infections and tuberculosis. It is difficult to unmask the fungus because it is not easily cultured nor is there a reliable serologic test. Therefore, a biopsy is required and the pathologist must recognize the large (ranging in size from 50 to 500 microns), round, Gomori methenamine-silver nitrate and periodic acid-Schiff reagent-positive spherules with a trilaminar wall. The spherules can be surrounded by either suppuration, epithelioid granulomas with or without necrosis, or concentric, hyalinized fibrosis. In the latter chronic stage, the organism may collapse, forming a variety of sizes and shapes thereby resembling other fungi, helminths, mineral particles, or inhaled pollen grains. Clinically, the infection most commonly regresses spontaneously, but may persist, or rarely progress, requiring surgical intervention with limited resection to attain cure. PMID- 8352374 TI - Immunoperoxidase staining of non-Hodgkin's lymphomas for T-cell lineage associated antigens in paraffin sections. Comparison of the performance characteristics of four commercially available antibody preparations. AB - Paraffin sections of 133 cases of non-Hodgkin's lymphoma (69 B-cell type and 64 T cell type) were stained in a labeled streptavidin biotin immunoperoxidase technique with a panel of antibodies that recognized T-lymphocyte associated antigens. This study was done to determine the sensitivity and specificity of these reagents for phenotyping T-cell lymphomas. UCHL-1, polyclonal anti-CD3, Leu 22, and OPD4 stained 78%, 72%, 91%, and 69% of the cases of T-cell lymphomas, respectively. The phenotype of L-26 negative and CD3 or UCHL-1 positive accurately predicted T-cell phenotype in 95% (60 of 63) of the T-cell lymphomas and was not seen in any of the cases of B-cell lymphoma. Although Leu-22 was the most sensitive T-cell-associated marker in this series, its lack of specificity for T-lymphocytes limited its usefulness as part of a routine panel designed to distinguish between T-cell and B-cell lymphomas. In conjunction with other reports, this study supports the use of the T-cell markers CD3 and UCHL-1 in combination with the B-cell-associated marker L-26 to phenotype most efficiently non-Hodgkin's lymphomas in paraffin sections. PMID- 8352375 TI - Sarcomas with combined features of liposarcoma and leiomyosarcoma. Study of two cases of an unusual soft-tissue tumor showing dual lineage differentiation. AB - Two cases are described of a soft-tissue sarcoma characterized histologically by the intimate admixture of areas displaying the features of liposarcoma and leiomyosarcoma. Both cases occurred in men, 70 and 77 years of age. The lesions were located in the left scrotum and abdominal cavity, respectively. Histologically, the lipomatous component in both cases consisted predominantly of well-differentiated liposarcoma with myxoid areas. The smooth-muscle component was characterized by intersecting fascicles of spindle cells displaying nuclear atypicality and scattered mitotic figures; the spindle cells in these areas were strongly immunoreactive with actin and desmin antibodies. The above tumors must be distinguished from angiomyolipoma, spindle-cell lipoma, myolipoma of soft tissue, and more importantly, from "dedifferentiated" liposarcoma. The development of dual lineage differentiation within adipose tissue tumors as exemplified by these two cases may be more prevalent than has been generally recognized, and may require the application of immunohistochemical markers for specific identification of the spindle-cell component. PMID- 8352376 TI - Necrobiotic palisading suture granulomas simulating rheumatoid nodule. AB - Five patients without clinical evidence of rheumatic disease developed postoperative periarticular suture reactions featuring necrobiotic granulomas histologically similar to rheumatoid nodules. Suture granulomas are to be included in the differential diagnosis of palisading granulomas simulating rheumatoid nodule. PMID- 8352377 TI - Massive chondroid differentiation in fibrous dysplasia of bone (fibrocartilaginous dysplasia) AB - Eight cases of fibrocartilaginous dysplasia (fibrous dysplasia with massive cartilaginous differentiation) of bone are reported. The age of the patients ranged from 4 to 26 years, with an average of 17.5 years. The male/female ratio was 1:1. In two patients the lesions occurred in a setting of polyostotic fibrous dysplasia. The anatomic sites most frequently affected were the femur and tibia. The proximal femur was the most common site. Roentgenograms showed well demarcated lucent lesions of ground-glass opacity. In addition, stippled or ring like calcifications suggesting cartilaginous elements were seen in six cases. Histologically, hyaline cartilage islands were found in juxtaposition to a fibro osseous lesion characteristic of fibrous dysplasia. Enchondral ossification was commonly seen, frequently showing columnar arrangement of cartilage cells mimicking a growth plate. The cartilage may show moderate atypism. The important thing is to recognize the benign nature of chondroid elements in fibrous dysplasia. Even if cartilage dominates the histologic picture, it is important to identify the fibro-osseous elements and thereby avoid the misdiagnosis of chondrosarcoma. PMID- 8352378 TI - Dracunculosis of the broad ligament. A case of a "parasitic leiomyoma". AB - This report describes the case of a 29-year-old Nigerian woman with dracunculosis presenting as an adnexal mass. The patient had a history of two second-trimester spontaneous abortions for which she was being evaluated. During the evaluation, she was found to have multiple uterine leiomyomas and a calcified left adnexal mass by pelvic ultrasound and radiography. At laparotomy, the calcified mass was excised from the left broad ligament, and a myomectomy was performed. Histologic examination revealed a calcified, coiled guinea worm embedded in the fibrous tissue of the broad ligament. Only one other case of calcified guinea worm in the broad ligament has been reported in the literature. PMID- 8352379 TI - Carcinosarcoma of the adrenal cortex presenting with mineralocorticoid excess. AB - An adrenal carcinosarcoma is reported in a 79-year-old woman presenting with clinical signs of hyperaldosteronism. The tumor weighed 199 g and consisted of areas typical of adrenal carcinoma and areas of sarcoma. The sarcomatous component of the tumor showed osteogenic and chondroid differentiation. Vimentin stained both the carcinomatous and sarcomatous regions. Four months after resection, the patient developed metastases. This is the third reported case of adrenal carcinosarcoma and the only case in which hyperaldosteronism or bony differentiation was observed. PMID- 8352380 TI - Elastofibromatous lesion. PMID- 8352381 TI - Regression of hepatic lesions after treatment of Schistosoma mansoni or Schistosoma japonicum infection in mice: a comparative study. AB - Experimental infections with Schistosoma mansoni and S. japonicum differ in several aspects and post-treatment resorption of fibrosis might be one of them. To investigate this point, mice infected with each of these schistosome species were treated with praziquantel and the evolution of hepatic lesions was sequentially followed for five months. Parasitologic data showing destruction of worms and eggs and biochemical findings of progressively decreased collagen concentration after cure indicated that the lesions caused by S. mansoni and S. japonicum involuted in a similar fashion following chemotherapy. The time sequence of the histologic changes indicative of decreasing inflammation and progressive matrix degradation and resorption was also similar in both cases. PMID- 8352382 TI - Falciparum malaria: differential effects of antimalarial drugs on ex vivo parasite viability during the critical early phase of therapy. AB - A method of monitoring Plasmodium falciparum viability ex vivo was used to compare the ability of different antimalarial drugs to arrest the progression of young parasites to mature, potentially damaging stages. Neither pyrimethamine sulfadoxine nor quinine, the treatment of choice for severe, life-threatening malaria, had a demonstrable effect on circulating parasites during the first 24 hr of therapy. In contrast, in vivo exposure to halofantrine for as little as six hours was sufficient to arrest parasite development. The method of assessing ex vivo parasite viability permits a comparison of antimalarial drug action at a time that may be critical for the therapy of life-threatening disease. If parenteral formulations of halofantrine prove to be safe and effective, they may have a role in the therapy of severe malaria. PMID- 8352383 TI - A novel pyrrolidonoalkaneamine (WR268954) that modulates chloroquine resistance of Plasmodium falciparum in vitro. AB - With the recent observations of efflux of chloroquine from Plasmodium falciparum and modulation of chloroquine resistance by calcium channel blockers, such as verapamil, a great deal of attention has been focused on the development of new modulators that can potentiate the efficacy of chloroquine. We report a new compound, WR268954, that has weak intrinsic antimalarial activity compared to chloroquine. In vitro, it increased the susceptibilities of chloroquine-resistant P. falciparum strains to chloroquine and quinine, but did not affect the chloroquine-susceptible strains. In the presence of 2,000 nM of WR268954, the 50% inhibitory concentration of chloroquine for drug-resistant P. falciparum decreased 90-fold in comparison with the control (chloroquine only). The same concentration of WR268954 increased the potentiation of chloroquine in resistant strains to a level approximately equivalent to that observed for the sensitive strain. This compound also potentiates the efficacy of quinine in drug-resistant parasites. However, WR268954 did not enhance the efficacy of mefloquine in the mefloquine-resistant parasites. In this report, the data show the synergistic effect of WR268954 on the antimalarial activity of chloroquine in drug-resistant strains of P. falciparum, but only an additive effect on drug-sensitive strains of parasites. Compound WR268954 belongs to a pyrrolidino alkane amine class whose in vitro chloroquine resistance modulator activity supports the basis for the synthesis of this class of compounds. PMID- 8352384 TI - PS-15: a potent, orally active antimalarial from a new class of folic acid antagonists. AB - A new, orally-active inhibitor of dihydrofolic acid reductase (DHFR), PS-15 (N-(3 (2,4,5-trichlorophenoxy)propyloxy)-N'-(1-methylethyl)- imidocarbonimidic diamide hydrochloride), has significant activity against drug-resistant Plasmodium falciparum. It is not cross-resistant with other inhibitors of DHFR (e.g., pyrimethamine and cycloguanil). Although it bears similarities to proguanil, PS 15 represents a new antifolate class of drugs that we have named oxyguanils or hydroxylamine-derived biguanides. This compound displays intrinsic antimalarial activity and also is metabolized in vivo to WR99210, an extremely active triazine inhibitor of DHFR. When tested in vitro against drug-resistant clones of P. falciparum, PS-15 was more active than proguanil, and the putative metabolite, WR99210, was more active than the proguanil metabolite cycloguanil. The drug is also more active as well as less toxic than proguanil when administered orally to mice infected with P. berghei. When administered orally to Aotus monkeys infected with multidrug-resistant P. falciparum, PS-15 was more active than either proguanil or WR99210. In 1973, WR99210 underwent clinical trials for safety and tolerance in volunteers. The trials showed gastrointestinal intolerance and limited bioavailability; further development of the drug was abandoned. Because PS-15 has intrinsic antimalarial activity, is not cross-resistant with other DHFR inhibitors, and can be metabolized to WR99210 in vivo, oral administration of this new drug should circumvent the shortcomings and retain the advantages found with both proguanil and WR99210. PMID- 8352385 TI - Plasmodium coatneyi ring-infected erythrocyte surface antigens. AB - Plasmodium coatneyi produced ring-infected erythrocyte surface antigen (RESA) during infection of the rhesus monkey. This antigen was immunogenic and elicited an antibody response that was not persistent but was boosted by repeated infections in a manner similar to that seen in P. falciparum infections in humans. Preliminary data showed that the appearance and increasing titer of antibodies to P. coatneyi RESA-like antigen were associated with prolongation of intervals from inoculation to patency and with control of parasitemia. Studies using both immunofluorescence assay and Western blot analysis showed that P. coatneyi-immune rhesus serum cross-reacted with P. falciparum antigens, but P. falciparum immune human serum did not recognize P. coatneyi antigens in either assay. These results show that P. coatneyi expresses RESA-like antigen that elicits an antibody response similar to that observed for human antibody to P. falciparum RESA. However, antibodies to P. coatneyi did not cross-react with P. falciparum RESA in erythrocyte membrane immunofluorescence assay and dot immunoblot analysis, suggesting that different immunogenic epitopes are present on the two molecules. Our observations support the use of this primate model in RESA-based vaccine development. PMID- 8352386 TI - Elevated antifilarial IgG4 antibody levels in microfilaremic and microfilaridermic Gabonese adults and children. AB - Immunologic analyses of sera from 47 selected individuals living in a mixed filariasis transmission zone in Gabon were carried out. Onchocerca volvulus, Loa loa, Mansonella streptocerca, and M. perstans are transmitted in this region. Based on parasitologic findings and age, the 47 individuals were stratified into four groups: microfilaria negative (Mf-) children (3-15 years old), Mf- adults (> 15 years old), microfilaria positive (Mf+) children and Mf+ adults. For descriptive purposes, the term microfilaria positive refers to individuals with skin and blood microfilariae. Antifilarial antibody titers were determined using an enzyme-linked immunosorbent assay with Dipetalonema viteae antigens. In general, children had higher titers of IgG antibodies than adults. For the IgG1, IgG2, and IgG3 subclass responses, both age and microfilarial status appeared to be important variables since Mf- children consistently had the highest titers whereas Mf- adults had the lowest titers. For the IgG4 antifilarial response, only the microfilarial status was an important variable. All Mf+ individuals had significantly higher levels of IgG4 antibody than Mf- individuals. Pooled sera of Mf- and Mf+ individuals reacted with similar O. volvulus antigens on Western blots. Control sera of individuals who did not reside in the study area, but who had single infections with L. loa or M. perstans, did not react with any O. volvulus antigens. PMID- 8352387 TI - Field trial of vaccination against American trypanosomiasis (Chagas' disease) in dogs. AB - In Santiago del Estero, an area endemic for Chagas' disease in northwestern Argentina, household dogs were vaccinated with live-attenuated Trypanosoma cruzi, and the prospective incidence of natural infection by this parasite was assessed during a two-year followup period. Vaccinated dogs received 10(7) attenuated, TCC strain T. cruzi epimastigotes and were given booster vaccinations two and 14 months later. The number of animals that could be evaluated in vaccinated versus control groups was 73 and 75 after one year and 49 and 40 after two years, respectively. Parasitologic evaluation by xenodiagnosis indicated that vaccination had reduced natural T. cruzi infection from 26.7% to 12.3% after one year (P = 0.015). The preventive effect of vaccination after the second year was less significant in spite of the booster vaccinations. Inclusion of indirect hemagglutination data for the diagnosis of infection slightly increased the number of infected dogs without affecting the evidence for protection in the first year. Serologic, parasitologic, and isoenzyme studies indicated that protection was mediated by an attenuated, self-cured infection. In 15 dogs in which the vaccination failed to completely prevent natural infection, immunization nevertheless impaired their ability to infect the natural insect vectors of the disease in humans. PMID- 8352388 TI - Factors affecting exflagellation of in vitro-cultivated Plasmodium falciparum gametocytes. AB - The environment of Plasmodium falciparum gametocytes changes when they make the transition from the vertebrate to the invertebrate host. Gametocytes of this species cultivated in vitro were used to evaluate the effect of serum, pH, pCO2 tension, bicarbonate ion, and temperature on gamete formation. Temperature was the only factor responsible for keeping P. falciparum gametocytes in the inactivated state. Mature gametocytes held at temperatures above 30 degrees C remained quiescent in 10% serum, even at low ambient pCO2 tension, alkaline pH, and in the presence of 25 mM bicarbonate ion. When the temperature of the medium was allowed to drop below 30 degrees C, gametocytes emerged from the red blood cells and microgametocytes consistently exflagellated at pH 7.4, even in the absence of bicarbonate ion. With regard to bicarbonate ion, exflagellation in P. falciparum is similar to P. berghei and different from P. gallinaceum gametocytes, which have an obligate requirement for bicarbonate ion. PMID- 8352389 TI - Epidemiologic aspects of a St. Louis encephalitis epidemic in Jefferson County Arkansas, 1991. AB - In 1991, the first epidemic of St. Louis encephalitis (SLE) ever reported in Arkansas resulted in 25 cases in Pine Bluff (attack rate: 44 per 100,000; 95% confidence interval [CI] 28-65). To identify risk factors for SLE viral infection and risk factors for neuroinvasive illness, we conducted a community-based, cross sectional study of noninfected and asymptomatically infected persons and a case control study of asymptomatically and symptomatically infected persons. The SLE viral infection rate was similar in all age groups and in all studied census tracts. Risk factors for asymptomatic infection included: living in a low income household (relative risk [RR] = 2.6, 95% CI 1.1-6.0), sitting outside in the evening (RR = 2.1, 95% CI 1.0-4.8), and living in homes with porches (RR = 2.9, 95% CI 0.9-9.3) or near open storm drains (RR = 2.2, 95% CI 1.0-4.9). Compared with asymptomatically infected persons, symptomatic persons were older (odds ratio [OR] for age > or = 55 years = 13.0, 95% CI 1.2-334) and more likely to have a previous history of hypertension (OR = 8.5, 95% CI 1.1-72). Our results indicate that advanced age is the most important risk factor for developing encephalitis after infection with SLE virus. Hypertension and vascular disease may predispose to neuroinvasive disease, but this epidemiologic study has not ruled out the confounding effects of age. PMID- 8352390 TI - Entomologic investigations of an epidemic of St. Louis encephalitis in Pine Bluff, Arkansas, 1991. AB - An epidemic of St. Louis encephalitis (SLE) occurred in Jefferson County, Arkansas during July-August 1991. At least 26 human cases were involved, with 25 cases in the town of Pine Bluff. Twelve isolates of SLE virus were obtained from mosquitoes collected in Pine Bluff between August 13 and 24: 11 from pools of Culex pipiens quinquefasciatus, resulting in a minimum infection rate of 1.6 per 1,000 (n = 6,768) for this subspecies, and one isolate from a pool of 22 mosquitoes identified as Cx. (Culex) spp. Three of the SLE-positive pools, two from Cx. p. quinquefasciatus and one from Cx. (Cux.) spp., also yielded isolates of Flanders virus. Larval surveys resulted in the collection of seven species in four genera from 28 larva-positive habitats and the identification of one significant site of Cx. p. quinquefasciatus production. Ecologic assessments conducted at 12 randomly selected residences resulted in the identification of 17 larva-positive habitats, for an average mosquito-positive habitat rate of 1.4 per residence, and a Cx. p. quinquefasciatus larva-positive habitat rate of 0.6 per residence. Aedes albopictus and Cx. p. quinquefasciatus were the species most frequently encountered in larval surveys in residential neighborhoods. PMID- 8352391 TI - Avian hosts of St. Louis encephalitis virus in Pine Bluff, Arkansas, 1991. AB - An investigation of the extent of St. Louis encephalitis (SLE) virus activity in the avian population in Pine Bluff, Arkansas was conducted from August 30, 1991 through September 5, 1991, following an SLE epidemic that resulted in 25 human cases. A total of 363 birds of 33 species were captured with ground-level mist nets at four sites along the northern edge of the city. No viruses were isolated from the serum of these birds, but 91 birds (25%) of 11 species had detectable neutralizing antibody against the TBH-28 strain of SLE virus in the constant virus, serum-dilution, plaque-reduction neutralization test in Vero cell culture. No antibody to eastern equine encephalitis virus was detected. The prevalence of antibody to SLE virus varied among the sites from 11% to 44%, but the prevalence at each site was influenced by the avian species composition. The two most abundant species captured in the city, the American robin (43%) and house sparrow (42%), also had the highest prevalence of antibody. Nine other bird species were serologically positive but at significantly lower rates than for the abundant species. The antibody prevalence was higher in immature birds (27%) than in adult birds (15%), but the antibody titers were higher in adult birds than in immature ones. The overall SLE antibody prevalence and the prevalence for house sparrows were significantly higher than the average prevalence for avian hosts studied during previous SLE epidemics. Therefore, house sparrows would be a good choice for a local sentinel species. PMID- 8352392 TI - Vector and host relationships of California serogroup viruses in western Siberia. AB - During 1990 and 1991, adult mosquitoes were collected along the Ob River and its tributaries in western Siberia from approximately 51 degrees 18'N to 66 degrees 4'N. Fifteen virus strains were isolated from 74,196 mosquitoes tested in 1,874 pools. These included Tahyna virus from Aedes cataphylla-punctor subgroup (one) and Ae. excrucians (one), and Inkoo (INK) virus from Ae. communis (one), Ae. communis subgroup (one), Ae. hexodontus (two), Ae. punctor subgroup (two), Ae. punctor complex (one), and unidentified Aedes species (three). In addition, a single Ae. euedes yielded a strain of snowshoe hare (SSH) virus and a strain of Getah, an alphavirus. A Bunyamwera serogroup virus was isolated from Ae. excrucians. With the exception of the two isolates from a single mosquito, minimum infection rates among mosquito taxa ranged from 0.4 to 16.7 per 1,000. The INK virus isolates were widely distributed geographically; however, seven of the 10 isolates were from two sites north of the Arctic Circle. During 1991, sera from two mouse species, five vole species, and four shrew species were collected along the upper Ob River for serologic tests. The prevalence of neutralizing antibody to SSH virus in these sera was 80%. Prevalence rates in the four most abundant species were Apodemus agrarius, 73%; Clethrionomys rutilus, 71%; Microtus arvalis, 80%; and Sorex araneus, 91%. This is the first attempt to clarify the vector and vertebrate host relationships of California serogroup viruses in western Siberia. PMID- 8352393 TI - Cryptosporidium infections in a suburban community in Maracaibo, Venezuela. AB - A point prevalence survey for Cryptosporidium was conducted in 212 subjects two months to 70 years of age in a suburban area with a low socioeconomic status in Maracaibo City, Venezuela. Single stool specimens were collected and modified Ziehl-Neelsen carbol-fuchsin staining of 10% formalin-preserved stool was used to identify Cryptosporidium oocysts. Direct wet mounts, iron-hematoxylin-stained smears and formalin-ether concentrates were examined to determine the presence of other intestinal parasites. Cryptosporidium infections were identified in 21 subjects (9.9%), with a high percentage of asymptomatic carriers (15 of 21, 71.4%). Six children (28.5%) had gastrointestinal symptoms and four of them were infants. Cryptosporidium was the single detectable potential pathogenic parasite in only five (23.8%) of 21 patients. The infection rate with one or more parasites was high (82%) and multiple infections, including pathogenic helminths and protozoa, were observed in the majority of patients who passed oocysts. Our findings suggest that although Cryptosporidium is an important pathogen, the proportion of asymptomatic carriers may be high in areas of low socioeconomic status in developing countries. PMID- 8352394 TI - Host preferences of the sand fly Lutzomyia longipalpis at an endemic focus of American visceral leishmaniasis in Colombia. AB - Blood meals from 579 Lutzomyia longipalpis (Diptera:Psychodidae), collected in an endemic focus of American visceral leishmaniasis in Colombia, were identified by precipitin test. Sand fly collections were made during a 16-month period from the inside walls of two houses, a pigpen, and rock crevices in a small community (El Callejon) within the endemic area. Feeding patterns of the sand flies varied with locality and date of collection. Overall, bovine feedings predominated, but feedings were also recorded on pigs, equines, humans, dogs, opossums, birds, and reptiles. Calculation of the forage ratios for each host species indicated that cows and pigs were the preferred hosts of Lu. longipalpis in El Callejon. Results of this study suggest that Lu. longipalpis is an opportunistic feeder and is not highly anthropophilic nor strongly attracted to dogs. PMID- 8352395 TI - Recent trends in the prevalence and distribution of schistosomiasis in the Nile delta region. AB - In 1983, a survey of 71 villages in the Nile delta demonstrated that the overall prevalence of Schistosoma mansoni and S. haematobium infections was 39% and 5%, respectively. Recent increased availability of praziquantel, combined with Egyptian Ministry of Health-sponsored media efforts to educate the public about schistosomiasis, prompted us to determine the current status of S. mansoni and S. haematobium infections in the delta and evaluate any changes that may have occurred since the previous survey. The same villages that participated in the 1983 survey were resampled in 1990. Stool and urine samples were requested from all occupants over the age of two years in a 5% sample of houses within each village. Stool (Kato) thick smears and urine sediments were read qualitatively at the rural health station. Field-prepared Kato smears and a 20% sample of urine specimens were forwarded to the Ministry of Health Laboratory, where quantitative readings were also performed. Analysis of samples obtained from 17,310 persons revealed that S. mansoni prevalence had decreased to 23% and that S. haematobium prevalence had decreased to 3% (P < 0.001). The highest levels of schistosome infection were found in governates located in the eastern section of the delta. The observed changes in the prevalence of S. mansoni and S. haematobium suggest that control measures are having a favorable impact on schistosomiasis transmission in this region. PMID- 8352396 TI - Mycoplasma pneumoniae and Chlamydia trachomatis in acute lower respiratory infections in Filipino children. AB - The role of Mycoplasma pneumoniae and Chlamydia trachomatis in acute lower respiratory infection (ALRI) was studied by serologic analysis of 216 Filipino children less than five years old living in periurban slums and middle-class neighborhoods. Diagnostic antibody responses to M. pneumoniae and C. trachomatis were observed in 18 (8.3%) and five (4.3%), respectively, of the cases with ALRI. These bacteria are not susceptible to the antimicrobial treatments currently recommended for the treatment of ALRI in developing countries. PMID- 8352397 TI - Common diarrhea pathogens and the risk of dehydration in young children with acute watery diarrhea: a case-control study. AB - The role of common diarrheal pathogens in dehydration was examined in children with acute watery diarrhea who attended the treatment center of the International Centre for Diarrhoeal Disease Research, Bangladesh, in Dhaka. Two hundred sixty nine children with moderate or severe dehydration were matched with 700 children with no dehydration. Vibrio cholerae O1 infections were 5.5 times more likely to be associated with dehydration than in cases without this agent. No significant association could be found between the presence of enterotoxigenic Escherichia coli. Campylobacter jejuni, or rotavirus infection and dehydration. These results were obtained after simultaneously controlling for age, lack of oral rehydration therapy (ORT) at home, protein energy malnutrition, withdrawal of breast-feeding during diarrhea at home, poor housing, longer duration of diarrhea at home, and delay in reaching the treatment center. The cholera isolation rate was only 4.5% and thus explains only a small proportion of the cases of dehydration. In cholera endemic areas, a strategy to prevent dehydration in small children is needed to ensure correct use of ORT at home, prompt referral, and the use of a suitable antibiotic when cholera is clinically suspected. PMID- 8352398 TI - Allastair B. Karmody Award. Improved recovery of limb function with ATP/MgCl2 in an ischemic canine hind limb. AB - The ability of a solution of low-vanadium-content (less than 1 ppm) adenosine triphosphate and magnesium chloride (ATP/MgCl2) versus normal saline to improve recovery of function and reduce necrosis of skeletal muscle after severe ischemia was investigated in an in situ autoperfused canine hind limb model. The study consisted of 12 dogs divided into 3 study groups: nonischemic control (NIL) (n = 7 limbs), ischemic (IL) (n = 7 limbs), and ischemic ATP/MgCl2-treated (IATP) (n = 7 limbs). In groups IL and IATP, the limb was reperfused for 3 hours following 4 hours of complete ischemia. In IATP limbs, 200 mumol/kg of ATP/MgCl2 was infused upon reperfusion of the limbs, whereas IL limbs received a similar volume of normal saline at the time of reperfusion. Function was determined by stimulating the deep peroneal nerve and anterior tibial muscle and measuring the resultant isometric twitch contractile force of paw dorsiflexion. Muscle necrosis was evaluated by photographic analysis of sectioned anterior tibial muscle stained with nitroblue tetrazolium dye. ATP/MgCl2 significantly increased functional recovery (p < 0.01) and significantly reduced skeletal muscle necrosis (p < 0.01). This study suggests that ATP/MgCl2 may be useful in reducing the clinical sequelae of severe limb ischemia and reperfusion. PMID- 8352399 TI - Management of concomitant abdominal aortic aneurysm and gastrointestinal malignancy. AB - Selecting the most appropriate surgical approach for patients with abdominal aortic aneurysm (AAA) and gastrointestinal malignancy remains controversial. In an attempt to develop guidelines for the management of patients with these two simultaneous lesions, a retrospective review of patients who had concomitant AAA and gastrointestinal malignancy was undertaken. During the period from January 1985 to February 1993, 229 patients with AAA were admitted to our hospital. Among these, 19 patients (8%) had a gastrointestinal malignancy together with AAA and were divided into 2 groups. Group I was composed of 11 patients who underwent either a 1- or a 2-stage operation for both lesions. Group II was composed of eight patients who either underwent an operation for one lesion (six patients) or did not have any operation (two patients). Among group I, six patients underwent the two-stage operation. In four of the six patients, the malignancy was resected first. In the remaining two patients, the aneurysmectomy was performed first, because, in one patient, the aneurysm was more than 6 cm in diameter, and, in the other patient, the aneurysm was a saccular type. Among group I, five patients (two patients with gastric cancer, and one patient each with esophageal cancer, rectal cancer, and malignant lymphoma of the stomach) underwent a one-stage operation. In three of the five patients (two patients with gastric cancer and one patient with esophageal cancer), simultaneous resection was carried out by using segregated approaches, namely, the retroperitoneal approach for AAA and the transperitoneal approach for malignancy. Although the clinical characteristics of the patients were different, 8 of the 11 patients (73%) in group I are still alive, whereas only 1 of the 8 patients (13%) in group II is still alive. The principles of our surgical approaches for concomitant AAA and gastrointestinal malignancy are as follows: (1) The lesion that absolutely indicated urgent surgery was resected first. (2) If both lesions were asymptomatic, the malignancy was resected first. (3) Simultaneous resection using different approaches was useful in some patients with concomitant upper early gastrointestinal malignancy. (4) Both lesions need to be resected eventually for better long-term survival. PMID- 8352400 TI - Comparison of magnetic resonance angiography and contrast arteriography in peripheral arterial stenosis. AB - Magnetic resonance angiography (MRA) has recently been shown to be more sensitive than contrast arteriography in the detection of patent distal runoff vessels. This study compares MRA and contrast arteriography in evaluating the severity of stenotic lesions in peripheral arteries, which has not been previously investigated. Forty-eight arterial stenoses (19 patients) were identified, from the distal aorta through the crural vessels. Contrast arteriograms (anterioposterior projection) and MRA axial images were used to measure stenoses. Interobserver agreement of arteriogram readings was excellent (average weighted k = 0.87). Measurements of degree of stenosis as evaluated by MRA and contrast arteriography were analyzed by linear regression and Spearman rank correlation, which showed a high degree of correlation between the two diagnostic modalities (r = 0.83, p < 0.001; rs = 0.84, p < 0.001). These observations suggest that MRA is accurate in the evaluation of peripheral arterial stenosis when compared with the "gold standard" contrast arteriogram. In addition, MRA cross-sectional images provide information beyond that of conventional arteriography, showing details of plaque eccentricity and vessel wall characteristics. In the future, MRA may supplant diagnostic contrast arteriography for many patients. PMID- 8352402 TI - Acute lower extremity ischemia after cardiac surgery. AB - A retrospective review during a 5-year period (1987 to 1992) was conducted of all patients manifesting leg ischemia after major cardiac surgery. There were 7,620 procedures performed, and 65 (0.85%) patients (mean age: 65 years) were identified with acute ischemia. Diagnosis was made by physical examination, during which a cool pulseless extremity without pedal Doppler signals was noted in 63 of 65 patients (97%). An intra-aortic balloon pump (IABP) was inserted in 56 patients (86%). Treatment regimens included medical management (17), IABP removal (4), IABP removal and thromboembolectomy (24), thromboembolectomy and endarterectomy with patch angioplasty (10), femoral-femoral bypass (17), other bypasses (6), fasciotomy (10), and amputation (16). Morbidity was 92% and mortality was 46%. Mortality was 11% in those patients developing ischemia without an IABP. Acute leg ischemia after cardiac surgery is predictive of high morbidity and mortality. This reflects the compromised cardiac status and multi system disease. Treatment alternatives are based on the overall clinical status, degree of arterial insufficiency, and distribution of pre-existing peripheral vascular disease. However, ultimate limb salvage had no influence on overall patient survival in our study. PMID- 8352401 TI - Very distal bypass for salvage of the severely ischemic extremity. AB - Forty-six bypass grafts to tibial arteries distal to the ankle were performed in 35 patients for salvage of extremities threatened by gangrene or nonhealing ulcers (grade III, category 5) or ischemic rest pain (grade II, category 4). Most patients (80%) were diabetic, with severely calcified arteries, whom previously we would have considered as candidates for primary amputation. All reconstructions were performed with autologous saphenous vein. Inflow was from the common femoral artery in 5 (11%), the popliteal artery in 25 (54%), or the mid-tibial arteries in 16 (35%). Life-table analysis was used to calculate primary patency and limb salvage. Results were analyzed according to origin of inflow, outflow, or configuration of the conduit (in situ saphenous vein, n = 29 [63%], reversed saphenous vein, n = 11 [24%], or nonreversed saphenous vein, n = 6 [13%]). Overall cumulative primary graft patency at 2 years for all grafts was 72%, and the cumulative limb salvage rate was 89% for the same interval. No significant differences were seen in comparing grafts originating from the femoral or popliteal level with those arising from the tibial arteries. No significant differences were noted in graft patency or limb salvage among grafts with a posterior tibial, dorsalis pedis, or plantar artery outflow. No significant difference was noted between in situ saphenous vein grafts and reversed saphenous vein grafts. A significant decreased primary patency was noted for grafts performed with nonreversed, translocated saphenous vein. We conclude that bypass grafts to the ankle or foot vessels are beneficial and should be considered for limb salvage in extremities with gangrene, ischemic ulceration, or ischemic rest pain. In our experience, in situ saphenous vein grafts or reversed saphenous vein grafts performed similarly, whereas nonreversed saphenous vein grafts have a poorer prognosis. Vessel wall calcification requires a modification in technique for performance of these grafts but did not affect long-term performance or limb salvage, and thus should not be considered a contraindication to vascular reconstruction. The operative microscope was used in 61% (28 of 46) of these cases and found useful in creating these delicate anastomoses. Additional follow-up is needed to document the long-term results of these very distal reconstructions. PMID- 8352403 TI - Variations of the arterial anatomy of the foot. AB - Reconstruction of the arteries of the foot in patients with severe chronic arterial occlusive disease has become a routine and valuable procedure. However, it is frequently difficult to select the optimal site for the distal arterial anastomosis. In order to determine the most important anatomic variations of foot arteries and the relationship of the dorsalis pedis artery to crossing tendons, the following study was performed in 30 cadaver limbs of 17 persons (9 men and 8 women). Their mean age at death was 69.8 years (range: 42 to 93 years). Methods to evaluate anatomy included anatomic dissection, arteriography, and preparation of corrosion cast models. The latter was performed by injection of liquid plastic and catalyst into the tibial arteries followed by chemical debridement of the soft tissue of the foot. Photographs of the corrosion cast models were taken at various stages of soft tissue dissolution. The dorsalis pedis artery was absent in 6.7% of the cases, and the arcuate artery was absent in 33%. The dorsalis pedis artery arose from the peroneal artery in 6.7%. The dorsalis pedis artery crossed under the extensor hallucis longus tendon at the ankle in 54%, above the ankle in 43%, but below the ankle in only 3%. Our study suggests that the optimal site for the dorsalis pedis artery anastomosis on the foot is the segment distal to the ankle. PMID- 8352404 TI - A new look at intraoperative completion arteriography: classification and management strategies for intraluminal defects. AB - Completion arteriography is widely regarded as an essential component of infrainguinal bypasses. However, the significance of various intraluminal filling defects is poorly defined, and strategies for managing these defects are unclear. Completion arteriography was performed by a standard technique in 78 infrapopliteal bypasses and were evaluated prospectively for the presence of angiographic defects. Thirty-nine arteriograms (50%) had no visible abnormality (grade O). Six arteriograms (8%) had minimal (grade I) defects, i.e., round lucencies (bubbles) or valve leaflets. Eighteen arteriograms (23%) had moderate (grade II) defects, i.e., uniform smooth tapering (up to 90% of luminal diameter) of the graft or outflow artery, irregular intraluminal filling defect (less than 60% of luminal diameter) within the distal graft or its adjacent outflow artery, or incomplete or faint graft opacification. Fifteen arteriograms (19%) had severe (grade III) defects, i.e., total cutoff of graft or outflow artery opacification or irregular intraluminal filling defect (greater than 60%) in the distal graft or adjacent outflow artery. Completion arteriograms were further stratified for type of bypass and outflow characteristics. All 24 bypasses with grade I or grade II defects on completion arteriography had no further surgical treatment. However, the 18 bypasses with grade II defects on completion arteriography had minimal nonsurgical manipulations consisting of repeat arteriography without or with papaverine infusion or urokinase instillation. In all 18, repeat arteriography showed improvement in the defect. The 15 bypasses with grade III defects had further surgical intervention (graftotomy, thrombectomy, vein patching, interposition graft, or graft extension). One-month and 1-year patency rates for grafts with grade I and grade II defects (87% and 79%, respectively) were not significantly worse than those for the 39 grafts with no arteriographic abnormalities (87% and 82%, respectively). In contrast, grafts with grade III defects had significantly worse (p < 0.01) 1-month and 1-year patency rates (33% and 20%, respectively) despite aggressive surgical correction of the arteriographic defects. These results emphasize the value of repeat completion arteriography and minimal interventional strategies when grade I or II defects are seen on arteriography. The poor outcome with surgical correction of grade III defects suggests that completion arteriography may not always define the full extent of the problem or that the corrective surgical maneuvers were either incomplete or detrimental. PMID- 8352405 TI - Is the use of intraoperative post-reconstruction angiography following in situ saphenous vein bypass redundant? AB - The value of post-reconstruction intraoperative angiography after in situ saphenous vein bypass has not been clearly defined. A retrospective review of intraoperative completion angiography using a standard proximal bypass injection technique without inflow occlusion was performed on 298 in situ saphenous vein bypasses constructed over a 72-month interval to treat critically ischemic limbs. Abnormal operative angiograms were found on retrospective review in 55 cases (18%). Minor abnormalities such as distal arterial or vein conduit spasm (class I defects) were found in 26 bypasses (9%) and required no surgical intervention. An anastomotic buckle or extrinsic compression due to an adventitial band (class II defect) was seen in five bypasses (2%). Defects requiring a major surgical revision (class III) were seen in 24 instances (8%). These abnormalities included nine cases with intraluminal platelet thrombus and six with a significant anastomotic torsional abnormality. In addition, there were five bypasses anastomosed to unsuitable diseased segments of distal arteries. Three of 24 (12%) of the bypasses with class III angiographic abnormalities required further revision within the first month after surgery, after duplex scanning had identified hemodynamically significant abnormalities, compared with 14 of 274 (5%) early revisions of the remaining in situ bypasses. The 30-day primary patency rate for bypasses with class III angiographic abnormalities was 88%. This compares with a rate of 95% for the remaining bypasses. The difference was not statistically significant. The 30-day and 48-month secondary patency rates for bypasses undergoing an immediate intraoperative revision for a class III abnormality were 100% and 93%, respectively. These rates were equivalent to the secondary patency of the in situ bypasses without class III abnormalities. Although the incidence of significant (class II and class III) angiographic abnormalities was low (10%), these abnormal findings allowed immediate correction of a jeopardized bypass, with minimal sequelae. PMID- 8352406 TI - Advanced carotid disease in patients requiring aortic reconstruction. AB - Perioperative stroke is a devastating complication of abdominal aortic operations. Patients requiring aortic reconstruction with advanced carotid occlusive disease pose a particularly challenging management problem regarding timing of operations. All patients (n = 121) undergoing both carotid artery endarterectomy (CEA) and abdominal aortic reconstruction (AAR) within 1 year of each other between 1979 and 1989 were reviewed. The sequence of operation was analyzed to determine its effect on early and late outcome. CEA was the first operation in 99 patients (group I); AAR was performed first in 22 patients (group II). Age, gender, number, types of risk factors, and associated medical problems were similar in both groups. Indications for CEA were: transient ischemic attacks (TIAs), recent ipsilateral stroke, or high-grade asymptomatic carotid artery stenosis exceeding 80%. Indications for aortic operation included: abdominal aortic aneurysm, aortoiliac occlusive disease, and combined aortic and renovascular disease. There were five perioperative strokes, two in group I (2%) and three in group II (14%) (p < 0.04). All strokes occurred after AAR. There were five perioperative deaths (4%), four in group I (4%) and one in group II (5%). Overall survival was significantly greater in group I compared to group II (p < 0.04); 5-year survival was 77% and 51%, respectively. Multivariate analysis demonstrated age, hypertension, and diabetes to adversely affect survival; CEA as the first procedure, however, had a protective effect. Importantly, eight strokes occurred in group I in late follow-up, but only one was ipsilateral to the CEA. We conclude that CEA in selected patients who require AAR is safe, and, when performed prior to abdominal aortic repair, reduces perioperative stroke and may improve long-term survival. PMID- 8352407 TI - Carotid stump pressure, stump pulse, and retrograde flow. AB - In order to obtain a more comprehensive intraoperative hemodynamic profile and to predict hypoperfusion during carotid endarterectomy, stump pressure, stump pulse, and retrograde internal carotid flow were measured in 261 patients. Our results show a significant correlation between stump pressure and retrograde flow (p < 0.001), stump pressure and the presence of a stump pulse (p < 0.001), and retrograde flow and the presence of a stump pulse (p < 0.001). We also demonstrated a significant correlation between stump pressure (lower), retrograde flow (less), and the absence of a stump pulse in patients with contralateral carotid artery occlusion. There was no correlation between the indication for carotid endarterectomy and any hemodynamic measurement. The triad of stump pulse, stump pressure, and retrograde flow accurately reflects collateral blood flow when the carotid is cross-clamped. These determinations can be obtained at low cost and are easily and rapidly performed. A protocol for selective shunting in patients undergoing carotid endarterectomy with general anesthesia is suggested. PMID- 8352408 TI - Is there a conduit of preference for a bypass between the carotid and subclavian arteries? AB - The conduit of choice for a bypass between the carotid and subclavian arteries remains controversial. We retrospectively evaluated 32 patients who underwent bypass between the carotid and subclavian arteries. Perioperative mortality was limited to a single patient who sustained a myocardial infarction. Long-term follow-up (mean: 46 months) revealed an 87% stroke-free survival rate, a 74% neurologic symptom-free survival rate, and a 77% primary patency rate at 5 years. No overall difference was discerned between a prosthetic or autogenous vein conduit. However, in bypasses constructed from the subclavian artery to the level of the carotid bifurcation, 100% (nine of nine) of vein bypasses remained primarily patent compared with 40% (two of five) of prosthetic grafts (p < 0.05). No distinct patency difference was identified between a short vein or a prosthetic bypass constructed between the proximal common carotid artery and subclavian artery. A vein bypass results in superior patency compared with a prosthetic graft for longer bypasses constructed from the subclavian artery to the carotid artery bifurcation. PMID- 8352409 TI - Extrathoracic bypass procedures for proximal common carotid artery lesions. AB - During a 10-year period ending in December 1991, 31 extrathoracic bypass procedures were performed in 29 patients for proximal common carotid artery atherosclerotic stenosis or occlusion. This included 16 men and 13 women, with a mean age of 63 years. Indications for surgery included transient ischemic attacks in 23 patients (79%), nonfocal symptoms in 4 patients (14%), and asymptomatic proximal common carotid artery stenosis associated with near-total occlusion of the internal carotid artery in 2 patients (7%). Severe proximal stenosis or complete occlusion of the common carotid artery was demonstrated angiographically in all cases. Subclavian-to-carotid bypass was performed in 26 cases and carotid to-carotid bypass in 5 cases. Seventy-four percent of the bypass procedures were to the common carotid artery and 26% to the external carotid artery. Endarterectomy of the common carotid bifurcation was performed in conjunction with the bypass procedure in 13 cases and vertebral artery transposition in 2 other cases. Saphenous vein was used as the bypass conduit in 65% and prosthetic grafts in 35% of cases. There were no perioperative strokes or deaths in this series, and the mean postoperative hospital stay was 5 days. Follow-up ranged from 2 to 118 months (mean: 38.4 months). Graft occlusion occurred in two cases during the follow-up period (3-year patency rate: 90%), with recurrence of symptoms in one patient, which necessitated revision. Three patients had persistence or recurrence of symptoms despite patency of the graft, one other patient sustained a posterior circulation infarct, and there was one death unrelated to carotid vascular disease during the follow-up period. This experience shows that extrathoracic bypass procedures are safe and well tolerated for symptomatic proximal common carotid artery stenosis or occlusion. This method of reconstruction has excellent long-term patency and protection against further anterior circulation neurologic events. PMID- 8352410 TI - Carotid endarterectomy with an occluded contralateral carotid artery. AB - Five hundred twenty-six patients who underwent carotid endarterectomy were separated by reviewing those 81 (15%) patients with an occluded contralateral carotid artery and those 445 (85%) with nonocclusion. The population characteristics and surgical indications were similar between the occluded and nonoccluded groups. Ipsilateral plus contralateral perioperative stroke occurred during 11 of 445 operations (2.5%) in which the contralateral carotid was patent, and during which no patient was hemorrhagic. Those patients with contralateral artery occlusion had ipsilateral plus contralateral stroke in 4 of 81 cases of (4.9%) (NS). Intracerebral hemorrhage was responsible for two of four strokes after carotid endarterectomy with contralateral occlusion (p = 0.001). Restenosis to greater than 50% by duplex scanning was more rapid in the occluded group with primary closure (no patch) (p = 0.025) and for men (p = 0.025). Although perioperative safety is comparable, patients with contralateral carotid occlusion may have a greater risk of intracranial hemorrhage and a more rapid rate of restenosis in some subgroups. PMID- 8352411 TI - Magnetic resonance angiography in the preoperative evaluation of abdominal aortic aneurysms. AB - Magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) are noninvasive techniques of visualizing blood vessels without the use of intravenous contrast or ionizing radiation. This prospective study assessed preoperative MRA and MRI in the evaluation of 28 patients with abdominal aortic aneurysm (AAA). MRI and MRA accurately predicted the extent of cephalad AAA, the patency of the superior mesenteric artery, and the course of the left renal vein, but were less accurate in defining the extent of caudal AAA, flow of the inferior mesenteric artery, and multiple renal arteries. This study suggests that MRI and MRA are alternatives to the combination of angiography and computed tomographic scan in the preoperative evaluation of patients with suspected AAA and no evidence of mesenteric or renal ischemia. When combined with preoperative segmental Doppler arterial studies, an accurate surgical plan may be formulated. Further refinements in image acquisition and postprocessing software analysis will advance the use of MRI and MRA for complete evaluation prior to elective AAA repair. PMID- 8352412 TI - Transesophageal echocardiography for hemodynamic management of thoracoabdominal aneurysm repair. AB - Maintenance of cardiovascular stability during thoracoabdominal aneurysm repair remains a formidable challenge. Transesophageal echocardiography (TEE) has been shown to be an excellent method for detecting myocardial ischemia and assessing left ventricular volume. We examined the utility of TEE in a group of 17 patients from an overall series of 33 patients who underwent thoracoabdominal aneurysm resection between 1988 and 1992. The mortality rate was 9%, whereas the incidences of myocardial infarction and paraplegia were 13% and 6%, respectively. Intraoperative management was significantly altered by TEE data in nine patients. Two patients were noted to have mitral valve insufficiency, and one had transient ischemia-induced regional wall abnormalities. In six patients, Swan-Ganz-derived filling data failed to identify severe hemodynamic alterations that were noted on TEE. Five patients were hypovolemic and hyperdynamic, whereas one was in florid congestive heart failure. Further investigation is warranted to prospectively validate this technique. PMID- 8352413 TI - Financial impact of thoracoabdominal aneurysm repair. AB - We have reviewed our experience regarding hospital costs and reimbursement for 72 patients who underwent thoracoabdominal aneurysm repair. Preoperative risk factors, postoperative complications, length of stay, and source of reimbursement were recorded for all patients. Patients covered by Medicare resulted in a mean net institutional loss of $16,472 per patient, whereas a mean net profit of $17,847 per patient resulted from patients with commercial insurance. Factors associated with institutional financial loss were: age over 75 years, preoperative coronary disease, postoperative respiratory failure, and length of stay. By multivariate analysis, however, only length of stay was independently associated with institutional loss. PMID- 8352414 TI - Aortic replacement for abdominal aortic aneurysm in elderly patients. AB - Improvements in the operative mortality and morbidity rates in elective aortic replacement, which are largely a result of refinements in surgical technique and perioperative management, have allowed a more aggressive approach in the treatment of abdominal aortic aneurysm (AAA) in elderly patients. To evaluate this approach, we reviewed the records of 116 patients 80 years of age and older (range: 80 to 93 years) who consecutively underwent aortic replacement for AAA. Seventy-seven patients underwent elective aortic replacement with 8 complications and a 3% operative mortality rate (2 of 77). Emergent aortic replacement was performed in 39 patients (14 with symptomatic nonruptured AAA and 25 with ruptured AAA) with 12 complications. In this nonselective subset, there were eight deaths, for an operative mortality rate of 20% (symptomatic 14%, ruptured 24%). In comparison, 780 patients less than 80 years of age underwent aortic replacement during the same time period. Within this group, 622 patients who were treated on an elective basis had a similar operative mortality (2%) as did patients 80 years of age and older. On the basis of these results, we believe that elective aortic replacement in elderly patients is justified and can be achieved with low operative mortality and morbidity rates. We suggest that the chronologic age of the patient should not deter aortic replacement. PMID- 8352415 TI - Management of chyloperitoneum after abdominal aortic surgery. AB - Chyloperitoneum is a rarely reported complication of abdominal aortic surgery. From 1981 to 1992, we treated 5 cases of chylous ascites after operations on the abdominal aorta and reviewed 22 previously published cases. There were 22 men and 5 women, with a mean age of 63.8 years (range: 27 to 93 years). Twenty cases (74.7%) occurred after abdominal aortic aneurysm resection, 5 (18.5%) after aorto femoral bypass for occlusive disease, and 2 (6.8%) after resection of infected aortic grafts, 1 for occlusive disease and the other for infrarenal aortic aneurysm. Abdominal distention was the most common presenting symptom, occurring in 26 (96.3%) of 27 patients. The mean time from aortic operation to the development of symptoms was 18.5 days (range: 7 to 120 days). Diagnosis was confirmed by paracentesis, which yielded lipemic, sterile fluid in all patients. Therapeutic paracentesis was not successful when used alone, but, when combined with a medium-chain triglyceride (MCT) diet or total parenteral nutrition (TPN), it resulted in resolution of chyloperitoneum in 8 of 14 patients (57.2%). TPN alone or with paracenteses and/or diuretics was successful in 9 of 15 (60%) patients. Peritoneovenous shunts resolved chylous ascites in four of five patients not responding to diet and/or TPN but resulted in one death due to sepsis. Operative ligation of the injured lymphatic channel was successful in all five patients treated by laparotomy when nonoperative efforts failed. Chyloperitoneum resolved in all but two (7.7%) patients. There were five (18.5%) deaths, but only three (11.5%) were directly related to chylous ascites. Treatment with TPN resolved chyloperitoneum in all five of our own patients. We reached the following conclusions: (1) Chyloperitoneum is a rare complication of aortic surgery; (2) This disorder should be considered whenever persistent abdominal distention appears after aortic surgery; (3) The diagnosis is easily confirmed by paracentesis; and (4) Surgery to close the lymph fistula should be reserved for those patients in whom conservative therapy with MCT diets or TPN has failed. PMID- 8352416 TI - Comparison of operative reconstruction and percutaneous balloon dilatation for central venous obstruction. AB - To evaluate the efficacy of venous reconstruction versus percutaneous transluminal angioplasty for the treatment of obstruction of the superior vena cava and its major tributaries, we retrospectively reviewed the clinical course of 27 patients, of whom 13 underwent operative reconstruction and 15 had angioplasty (1 had both). Three patients had obstruction of the superior vena cava, 8 had occlusion of the innominate veins, and 16 had obstruction of the subclavian or axillary veins. In both treatment groups, mean age, indications, etiology, and location of the lesion were comparable. No major surgical complications occurred; one patient who underwent angioplasty experienced stent migration to the pulmonary artery without sequelae. Primary symptomatic relief at 1 year was achieved in 88% in the surgical group versus 36% in the angioplasty group (p < 0.05 by Fisher's exact test) and at 2 years in 71% versus 0%, respectively (p < 0.01). One- and 2-year success rates with repeated angioplasty, however, were 86% and 66% (p > 0.9), respectively. We conclude that the long-term success rate of operative reconstruction exceeds that of single percutaneous transluminal angioplasty. However, with repeated angioplasty, success rates approach those of operative reconstruction. PMID- 8352417 TI - Advances in the treatment of phlegmasia cerulea dolens. AB - Phlegmasia cerulea dolens (PCD) is an uncommon, severe form of lower extremity deep venous thrombosis characterized by extremity swelling, cyanosis, and pain. Progression of the thrombotic process may result in extremity gangrene, amputation, and death. The relative value of specific therapeutic regimens in the treatment of this disease remains uncertain. Twelve patients, 9 females and 3 males, with PCD were treated during a 10-year period. Eighteen lower extremities were involved. Pre-existing conditions included malignancy (eight), postoperative state (four), diabetes (three), previous deep venous thrombosis (three), and hypercoagulation (two). Venous gangrene was present in four patients. All patients were treated initially with bedrest, fluid resuscitation, extremity elevation, and systemic high-dose heparin therapy. Five patients had complete resolution with this regimen alone. One patient required cessation of heparin therapy due to heparin-induced thrombocytopenia and developed gangrenous toes. Two patients whose condition failed to respond to heparin therapy underwent catheter-based delivery of urokinase with marked clinical improvement. Four patients, two with venous gangrene, died, three of whom had disseminated malignant disease. A significant percentage of patients with PCD will respond to extremity elevation, fluid resuscitation, and aggressive systemic anticoagulation therapy. Thrombolytic therapy selectively administered is beneficial in patients whose disease fails to respond promptly. Venous thrombectomy should be reserved for patients with contraindications to thrombolysis. PMID- 8352418 TI - Production of endothelium-derived relaxing factor (EDRF) is compromised after ischemia and reperfusion. AB - Rabbit hind limbs were subjected to 5 hours of ischemia with or without 1 hour of in vivo reperfusion, and the response of femoral artery segments to vasocontrictors and vasodilators was studied in vitro. The ability of endothelium derived relaxing factor (EDRF)-dependent vasodilators to relax arterial segments was not altered after up to 5 hours of ischemia alone but was significantly decreased after 4 hours of ischemia if followed by 1 hour of in vivo reperfusion. Thus, we concluded that a specific injury occurs to endothelial cells after ischemia-reperfusion, which occurs solely during the reperfusion period. PMID- 8352419 TI - Pulse-spray pharmacomechanical thrombolysis for treatment of thrombosed dialysis access grafts. AB - The results of pulse-spray pharmacomechanical thrombolysis (PSPMT) of 209 thrombosed hemodialysis grafts were reviewed. In PSPMT, concentrated urokinase is injected forcefully through catheters with multiple tiny sideholes or sideslits. Catheters placed in a crisscross fashion cover the entire clot simultaneously. This therapy was successful in treating patients with thrombosed grafts. Of the 200 grafts with complete therapy, 197 grafts (99%) were patent at the end of the procedure. Mean time for pulsed-spray lysis was 40 minutes. Etiologies for graft thrombosis were anastomotic venous outflow stenosis, stenosis of the venous outflow away from the anastomosis, arterial stenosis, intragraft stenosis, pseudoaneurysms, and no identifiable cause in a small percentage. There were 16 complications, 8 of which required additional therapy or potentially compromised the graft. These results suggest that pharmacomechanical thrombolysis and angioplasty provide rapid, consistent, and safe recanalization of thrombosed hemodialysis grafts and represent an additional therapeutic approach to graft management. PMID- 8352420 TI - Celiac territory ischemic syndrome in visceral artery occlusion. AB - Abdominal angina that is characterized by postprandial pain, and often associated with weight loss, is a well-recognized symptom complex of mesenteric artery insufficiency (mesenteric territory symptoms). In the past 5 years, we have observed six patients with atypical symptoms who had mesenteric artery occlusion combined with stenosis or occlusion of the celiac artery. Atypical symptoms included severe nausea and vomiting at the sight or smell of food, anorexia, weight loss, and right upper quadrant or epigastric discomfort (celiac territory symptoms). An extensive work-up to rule out gastric, pancreatic, biliary, or colonic pathology was undertaken in these patients. The findings included gallbladder dysfunction, diffuse micro-ulceration of gastric mucosa, and colonic mucosal ulceration. The diagnosis of visceral artery occlusion was initially missed in all six patients. Four patients had cholecystectomy. Visceral angiography confirmed occlusion of the celiac, superior, and inferior mesenteric arteries. Five patients had dramatic resolution of symptoms after restoration of visceral circulation. One patient who developed intestinal infarction before revascularization died. Symptoms suggesting upper abdominal visceral pathology may be a manifestation of celiac artery stenosis/occlusion coexisting with mesenteric artery occlusive disease. Visceral angiography should be part of the work-up in these patients for early diagnosis and prompt management. PMID- 8352421 TI - Acute mesenteric ischemia after cardiopulmonary bypass. AB - Three thousand sixty-six patients underwent cardiopulmonary bypass at the Maimonides Medical Center over a 5-year period from January 1, 1987, to January 1, 1992. Of these patients, 1,890 (62%) were less than 70 years of age, 969 (32%) ranged from 70 to 79 years of age, and 207 (7%) were 80 years of age or older. The overall 30-day mortality rate was 8%. Eleven patients developed acute mesenteric ischemia from 24 hours to 12 days postoperatively. At the time of diagnosis, the majority of patients presented with late classical signs and symptoms of acute mesenteric ischemia including abdominal distension, respiratory distress, hypotension, oliguria, and sepsis. All patients underwent immediate laparotomy. Extensive bowel necrosis was found in all, and resection was possible in eight patients. All patients died as a result of this complication. Using the exact trend test, we found a statistically significant increase in the incidence of deaths due to acute mesenteric ischemia after cardiopulmonary bypass in older compared with younger patients. This fatal complication after cardiopulmonary bypass occurs more often than previously believed and is a relatively common cause of death in the elderly. PMID- 8352422 TI - Medical reservists in support of humanitarian effort. PMID- 8352423 TI - Hume Memorial Lecture. Surgeon's response to battlefield vascular trauma. PMID- 8352424 TI - Cell washing versus immediate reinfusion of intraoperatively shed blood during abdominal aortic aneurysm repair. AB - Significant hematologic changes are known to occur following intraoperative autotransfusion of shed blood, but the clinical importance of cell washing prior to reinfusion has not been substantiated. To evaluate these changes and their relationship to the use of blood bank products and postoperative morbidity, 26 patients undergoing elective abdominal aortic aneurysm repair were prospectively randomized to reinfusion with washed shed blood or to the use of a collection system in which filtered, but unwashed, whole blood was reinfused intraoperatively. Each patient was evaluated with respect to standard metabolic and hematologic laboratory parameters preoperatively, immediately postoperatively, and 12 to 18 hours postoperatively. Patient demographic data were similar for both groups. Perioperative survival was 100% for both groups. Total blood loss and blood volume autotransfused were significantly greater in the unwashed cell group compared with the washed cell group (p = 0.00014 and p = 0.00011, respectively). Hemoglobin, fibrinogen, prothrombin time, and partial thromboplastin time levels were not significantly different between the two groups at any time perioperatively; fibrin split product and d-dimer levels were significantly higher in the unwashed cell group postoperatively (p = 0.016 and p < 0.001, respectively). Serum free hemoglobin levels were significantly higher in the immediate postoperative period in the unwashed cell group compared with the washed cell group (p = 0.0013); by 12 to 18 hours postoperatively, this difference was not significant. Haptoglobin levels were significantly lower in the unwashed cell group at both postoperative times (123 +/- 86 mg/dL versus 41 +/- 50 mg/dL, p = 0.0086; 102 +/- 66 mg/dL versus 24 +/- 36 mg/dL, p = 0.0001); however, there was no perioperative renal failure in either group. Furthermore, homologous blood product use was not significantly different between the two groups, with an average of 1.5 +/- 2.5 units of packed red blood cells given to patients in the unwashed cell group versus 0.8 +/- 1.7 units in the washed cell group (p = 0.419). Overall complications were higher and critical care and total hospital stays were longer in the unwashed cell group but did not result from autotransfusion of unwashed blood. We conclude that the intraoperative reinfusion of unwashed shed blood is safe and effective, causing transient hematologic abnormalities that normalize in the early postoperative period, and is not associated with increased mortality, or hematologic, cardiopulmonary, or renal complications. PMID- 8352425 TI - Sperm antigens and reactivity of antisperm monoclonal antibodies in ELISA. AB - Several types of sperm antigenic suspensions as well as the whole sperm, either methanol-fixed or air-dried, were checked for intensity of binding to monoclonal antisperm antibodies with known characteristics of reactivity to sperm. The activity of sperm antigen--antibody binding was measured by ELISA (enzyme-linked immunosorbent assay) and compared in several variations (parallely run) of the assay where different types of sperm antigen preparations were applied. The obtained results were then evaluated for statistical significance in Wilcox test. It was shown that antibody reactivity was markedly higher in experiments where the whole sperm was coated in a solid-phase in comparison to results obtained with adhered different sperm antigenic suspensions. However, one exception was noted, where the results from ELISA, run with sperm organic extract, were (statistically) insignificantly lower than those obtained with the whole sperm. Therefore, organic sperm extracts (containing mostly glycolipids) can be a valuable alternative to screening for antisperm antibody activity and/or infertility background. PMID- 8352426 TI - The variability of measuring sperm concentration and motility as determined by computer assisted image analysis and visual estimation. AB - Systems of computer-assisted image processing (CAIP) offer good reproducibility and low intra-assay variability between replicate analyses of the same sample. The correlation between these values and those obtained by directly microscopic observation can be well demonstrated. The comparability between systems of different manufacturers is sufficient and satisfactory. Thus, they are well suited for the routine work in the andrologic laboratory. Since sperm parameters are used for the prediction of male fertility, it is important to know whether computer-assisted analysis improves the predictive power as compared to visual estimation. In our study we compared the variation of semen parameters between two semen samples of the same individual taken in an interval of at least 3 months, by using the CAIP and visual methods. Significantly close correlations between the two values were obtained by both methods. Values of cell concentration showed the highest correlation in both methods (r = 0.75). The lowest correlation, but also statistically significant, was observed in the values of locally motile cells (r = 0.54 for CAIP and r = 0.30 for visual determination). Although apparently higher in CAIP within method correlation coefficients did not show statistically meaningful differences between both methods. We conclude from our study that if values of sperm concentration and motility as measured by CAIP are compared to those obtained by visual measurement, the first method is not superior to the latter in terms of retest reliability. PMID- 8352427 TI - Sperm motility analysis using multi-exposure photography (MEP): validity of the method with normal and abnormal patterns. AB - Spermatozoon motility is an important semen parameter that can be correlated with fertilizing capacity. It can be evaluated by subjective or objective methods such as the multiple exposure photography technique (MEP). This technique was: (1) validated in terms of accuracy and sensitivity, and (2) used to investigate the possibility of differentiating patient subgroups on the basis of sperm motility. The method was shown to be accurate. The within and between assay variation coefficients were less than 6% and 17% respectively. Maximal sensitivity required 100 spermatozoa, since coefficients of variation were high when counting smaller numbers. A significant difference between fertile, normozoospermic and asthenozoospermic groups on the basis of the population pattern was found in a retrospective study. Moreover, the asthenozoospermic group could be divided into three subgroups, depending on whether one, two, or three motility variables were altered. PMID- 8352428 TI - Prognostic value of an automated sperm analysis in IVF or insemination therapy. AB - During the course of sterility treatment semenograms of 271 IVF and 316 insemination patients were carried out by two automated semen analysers. The parameters of these analyses were correlated to pregnancies resulting from the treatment. Semen samples were analysed in the ejaculate and after swim-up preparation. In addition, the swim-up suspension of IVF patients was measured again 18 h after sperm preparation. Patients were divided into three groups: (1) couples who achieved a pregnancy, (2) couples who did not achieve a pregnancy, and (3) IVF patients with no fertilization of the oocytes. Because of large standard deviations in the quality of ejaculates, the results in the IVF group show no significant differences in the semen parameters of husbands of pregnant and non-pregnant women. In contrast husbands of women with no fertilization have a significantly lower sperm motility. After swim-up preparation these differences no longer occur. A further measurement, taken 18 h later, reveals that there are no differences in the sperm parameters between the pregnant and non-pregnant group. However, the semen quality in the group with no fertilization is significantly reduced. The results of the insemination patients are similar to those of the IVF group. Thus, the results from automated sperm analysers cannot replace either the microscopic or biochemical analysis of an ejaculate and, moreover, cannot be used as prognosis for the fertilization capacity of sperms or a following pregnancy. PMID- 8352429 TI - Electron microscopic immunolocalization of a conserved sperm acrosomal antigen recognized by HS-63 monoclonal antibody. AB - HS-63 monoclonal antibody was shown to react with a sperm-specific acrosomal antigen from spermatozoa of a variety of mammalian species. Indirect immunofluorescence showed that HS-63 was associated with acrosome-intact sperm after sperm had been fixed with methanol. Electron microscopy (EM) was employed to determine the ultrastructural localization of this sperm antigen. When the immunogold labelled goat anti-mouse IgG was used as a probe, we demonstrated that HS-63 monoclonal antibody did not bind to the freshly prepared human spermatozoa. However, gold particles were observed in the intra-acrosomal region, when the spermatozoa had been pre-treated with 0.5% Triton X-100 prior to incubation with HS-63. We further observed that the immunogold did not stain the inner acrosome membrane when the spermatozoa became acrosome-reacted. A good correlation was obtained between the percentage of spermatozoa which did not react with HS-63 as determined by indirect immunofluorescence assay and that of acrosome-reacted spermatozoa as quantitated by electron microscopy. The results of this EM study were consistent with those obtained by indirect immunofluorescence assay and both indicated that HS-63 reacts only with the capacitated and acrosome-intact spermatozoa. Therefore, HS-63 monoclonal antibody is a useful probe for rapid evaluation of acrosomal status in human spermatozoa. PMID- 8352430 TI - Effect of intratesticular administration of anti-corticotropin-releasing factor antiserum (a-CRF) on testicular function in neonatal rats. AB - The possible physiological role of testicular corticotropin-releasing factor (CRF) in the regulation of testicular functions was studied in neonatal rats. Two microlitres of anti-CRF-antiserum (dilution: 1:10 or 1:100) was injected intratesticularly to 5 d-old rats with two testes and to hemicastrates. Five days after hemicastration and treatment of the remaining testis with the antiserum, serum testosterone concentration and basal testosterone secretion in vitro decreased significantly. Unilateral testicular injection of a-CRF in rats with two testes resulted in a significant drop in serum testosterone level with no change in basal testosterone production. Data indicate that in neonatal rats testicular CRF might be a local stimulator of steroidogenesis. PMID- 8352432 TI - Insulin, insulin resistance, and dyslipidemia. PMID- 8352431 TI - Laminin and aminoterminal propeptide of type III procollagen in seminal plasma from fertile and vasectomized men. AB - The components of the extracellular matrix, laminin and aminoterminal propeptide of type III procollagen (PIIINP) were determined in seminal plasma of 50 patients with vasectomy and of 50 age-matched fertile patients. The concentration of laminin was highly significantly (P < 0.001) elevated in the fertile group as compared to the vasectomy group, whereas the concentrations of PIIINP were not significantly different between these two groups. Only weak correlations were observed between the concentrations of laminin and PIIINP. It is suggested that part of the laminin found in seminal plasma is derived from the ductus deferens, while the source of PIIINP is probably located at an upper part of the urogenital tract. PMID- 8352433 TI - Effect of dietary lipid on insulin action. Clinical studies. AB - Evidence from the best studies available in the literature suggest that the isocaloric substitution of dietary fat for dietary carbohydrate does not cause insulin resistance. Although many studies show several differences between the diets (for example, changes in dietary fiber or fat subtype), the diets were primarily designed to compare the effects of the fat/carbohydrate content, and a true important effect of dietary fat on insulin action should have been detected. Some studies found other changes in carbohydrate metabolism such as improvements in insulin secretion and glucose effectiveness (Sg) that could contribute to the conflicting results. For example, glucose uptake as measured by the euglycemic clamp includes both insulin-dependent and non-insulin-dependent (SG) factors, so that the M value could be affected by changes in SG as well as in insulin action. All of these studies have used isocaloric substitution so that body weight is maintained. This constraint, while important for determining and direct effect of dietary fat, may lead to false conclusions about its overall effects on insulin action. One of the most common and potent causes of insulin resistance is obesity, and dietary fat is of singular importance in the genesis of obesity. Inasmuch as an ad libitum reduced fat diet causes weight loss, the overall effect of dietary fat reduction may be an improvement in insulin action because of weight loss even in the absence of any direct effects. Long-term studies of the effects of fat content within ad libitum diets are needed to place these largely negative results from isocaloric studies in context. PMID- 8352434 TI - Dietary fish oil and insulin action in humans. PMID- 8352435 TI - Dietary fat, carbohydrate balance, and weight maintenance. PMID- 8352436 TI - Risk factors for the development of obesity. PMID- 8352437 TI - Dietary lipids influence insulin action. AB - Insulin binding and insulin responsiveness are altered by dietary fat-induced changes in the fatty acid composition of the adipocyte plasma membrane. Feeding a high P/S diet increased polyunsaturated fatty acid content of major membrane phospholipids of adipocyte plasma membrane in normal and diabetic animals, increased membrane linoleic acid content, and prevented a decrease in arachidonic acid level in diabetic animals. The high P/S diet increased insulin binding in control animals. Animals fed the high P/S diet had significantly higher rates of insulin-stimulated glucose transport and lipogenesis than did animals fed the low P/S diet. Feeding a high P/S diet significantly increased the amount of glucose transported when expressed as a function of the specific amount of insulin bound. To determine if dietary fat-induced alterations in the fatty acid composition of skeletal muscle lipid alter insulin-dependent and basal muscle metabolism, contralateral epitrochlearis and extensor digitorum longus muscles were isolated and incubated in vitro. High levels of dietary omega-3 fatty acids reduced PGE2 and PGF2 alpha synthesis in extensor digitorum longus and epitrochlearis muscle. Insulin increased glucose and amino acid transport; the increase in glucose transport by insulin was significantly greater after consumption of the high omega-3 fatty acid diet. Rats fed high levels of omega-3 fatty acids showed reduced net protein degradation in the presence and absence of insulin due to decreased rates of protein degradation and synthesis. These experiments indicate that high levels of dietary omega-3 fatty acids alter muscle membrane composition, glucose transport, and metabolism of muscle protein. To determine if dietary fatty acids alter the onset of diabetes and insulin binding to liver nuclei in spontaneously diabetic rats, weanling rats were fed chow or semipurified diets containing 20% (w/w) fat of either high or low P/S ratio. Feeding a high P/S diet increased insulin binding to liver nuclei of control and diabetic animals. Although diet did not alter the onset of diabetes, insulin binding to liver nuclei is higher in animals at the onset of diabetes than in highly diabetic animals. Eight-week-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low P/S ratio to investigate the effect of diet on specific binding of insulin to liver nuclei. Insulin binding was highest in nuclei from lean mice fed a high P/S diet. Specific binding of insulin to nuclei from obese mice was also increased by the high P/S diet, but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352439 TI - Dietary intake of lipids, insulin secretion, and cellular lipid peroxidation and order parameters in humans. PMID- 8352440 TI - Effect of dietary fatty acids on LDL binding. PMID- 8352438 TI - N-3 fatty acids from fish oil. Effects on plasma lipoproteins and hypertriglyceridemic patients. AB - In the experimental studies reported in this review, dietary n-3 fatty acids from fish and fish oil had profound hypolipidemic effects in normal subjects and in hypertriglyceridemic patients with combined hyperlipidemia (type II-b) and types IV and V hyperlipidemia. In these carefully controlled metabolic experiments, dramatic reductions occurred in plasma triglycerides and to a lesser extent in plasma total cholesterol. Reductions in VLDL, chylomicrons, remnants, LDL, apo B, and apo E were also noted. HDL changes varied from subject to subject. These plasma lipoprotein changes occurred in subjects with non-insulin-dependent diabetes mellitus as well, without deterioration of diabetic control. Similar results are reported in two other papers in this volume. Fish oil did not cause deterioration of diabetic control. Whereas the mechanism of the hypolipidemic action of the n-6 rich vegetable oils containing linoleic acid such as corn or safflower oil still remains obscure, the mechanism of the hypolipidemic action of the n-3 fatty acids in fish oil is well documented. The synthesis of triglyceride and VLDL in the liver is greatly reduced by n-3 fatty acids. At the same time, the turnover of VLDL in plasma is shortened. In another study, LDL production was decreased. Combined with other dietary manipulations, such as a reduction in saturated fat and dietary cholesterol, the use of n-3 fatty acids to treat hyperlipidemia, especially hypertriglyceridemia, appears to have a well-supported rationale. Fish oil combined with a low cholesterol, low saturated fat diet has been shown to produce complementary effects. Total plasma cholesterol and LDL cholesterol were lowered by the low cholesterol, low saturated fat diet, whereas plasma triglyceride and VLDL were decreased by the fish oil. In most situations, the use of fish oil supplements should be regarded as pharmacologic therapy, particularly effective in severe hypertriglyceridemic states (e.g., chylomicronemia). However, a lifelong diet rich in fish may be protective against atherosclerosis as well. Further studies are required to delineate exact doses and precise indications for the use of fish oil in different types of hyperlipidemias and to differentiate the effects, if any, of the two major n-3 fatty acids in fish oil, EPA and DHA. The hypolipidemic effects of n-3 fatty acids coupled with their known antithrombotic actions (secondary to changes in prostaglandin secretion, platelet function, inhibition of growth factors, and enhancement of endothelial-derived relaxation factor) appear to have an important potential role in the control of coronary heart disease and other atherosclerotic disorders. Moreover, fish oil may prevent the "chylomicronemia" syndrome of type V hyperlipidemia. PMID- 8352441 TI - Dietary monounsaturated fatty acids for patients with diabetes mellitus. PMID- 8352442 TI - Effect of intravenous administration of docosahexaenoic acid emulsion on blood glucose and insulin concentrations in diabetic rats. PMID- 8352443 TI - Effect of dietary fish oil on insulin action in fat cells of control and non insulin-dependent rats. PMID- 8352444 TI - Effect of high fat feeding on glucose tolerance in neonatally streptozotocin treated rats at 3 and 6 months of age. AB - In the rat, a high fat intake is believed to be associated with an increased risk for the development of glucose intolerance by inducing insulin resistance. The aim of this study was to investigate whether reduced insulin production may also play a role. Rats were treated with 0, 30, 60, and 90 mg of streptozotocin (STZ)/kg of body weight on the day of birth (0, 30, 60, and 90 nSTZ rats). At 3 or 6 months of age, glucose tolerance was assessed by the intravenous glucose tolerance test (IVGTT). STZ dose-dependently decreased first- and second-phase insulin responses and correspondingly impaired glucose tolerance. Following a 3 week high fat diet (HFD: 60% of calories as corn oil), insulin responses were higher in control as well as in STZ-treated rats both at 3 and 6 months of age. In 3-month-old rats this was accompanied by unchanged or increased glucose levels following the glucose load, whereas in 6-month-old 0 and 30 nSTZ rats glucose tolerance was slightly improved. After 6 weeks of HFD in 6-month-old rats, glucose tolerance was impaired compared to that after 3 weeks of HFD despite higher insulin responses. Continuing the HFD for up to 12 weeks further impaired glucose tolerance, but insulin responses were decreased compared to those after 6 weeks of HFD. These results indicate that very low dose neonatal STZ administration impairs glucose tolerance through decreased overall insulin responses. This may possibly be due to a reduction of B-cell number rather than an alteration of B-cell function. No clear evidence exists that a high fat intake per se negatively influences glucose-induced insulin responses, but this may become apparent after longer periods of high fat feeding. PMID- 8352445 TI - Effect of dietary fish oil on 2-deoxy-D-3H glucose uptake in isolated adipocytes of rats fed various diets. AB - High sucrose diet-induced insulin resistance and mild glucose intolerance are associated with decreased insulin binding to isolated adipocytes and reduced insulin action in adipose tissue. Enhanced dietary intake of omega-3 polyunsaturated fatty acids (n-3-FA) counteracts these disorders. To provide more information on the possible role of membrane-related glucose transport processes, basal and insulin-stimulated 2-deoxy-D-3H glucose uptake was evaluated in isolated adipocytes obtained from rats on various dietary regimens. For 2 weeks animals were fed three different isocaloric (18 cal% proteins, 19 cal% fat, and 63 cal% carbohydrate) diets: (1) a standard rat chow (B), (2) a high sucrose diet (S, 63 cal% sucrose), or (3) an S diet supplemented with marine fish oil (S + FO, Martens, 30 wt% of n-3-FA). High dietary n-3-FA intake resulted in a significant decline in both basal (0.05 +/- 0.01 pmol/10(6) fat cells; mean +/- SEM) and insulin-stimulated (10(-6) M) (0.20 +/- 0.01) glucose uptake when compared with the control (basal: 0.12 +/- 0.02; insulin: 0.35 +/- 0.02) and/or the S group (basal: 0.18 +/- 0.03; insulin: 0.43 +/- 0.03), indicating decreases in insulin responsiveness and sensitivity (ED50: B: 0.03 +/- 0.01; S: 0.03 +/- 0.01; S + FO: 0.73 +/- 0.2 nM; p < 0.01 for S + FO vs B and S + FO vs S). Fish oil supplementation induced an increase in adipocyte size (B: 69 +/- 1.6; S: 70 +/- 2.5 and S + FO: 76 +/- 2.2 microns; B: S + FO p < 0.05) and a decrease in plasma membrane microviscosity (B: 4.08 +/- 0.3; S: 5.39 +/- 0.5; S + FO: 3.10 +/- 0.3; p < 0.05). Rates of basal and insulin-stimulated glucose uptake did not correlate with plasma membrane microviscosity; however, a negative relation to fat cell size was found (r = -0.484; p < 0.05). On the other hand, a positive correlation between both basal (r = 0.504; p < 0.05) and insulin-stimulated (10(-6) M, r = 0.640; p < 0.02) glucose uptake and blood glucose levels was observed. In conclusion, these data (a) suggest a less important role of diet-induced changes in plasma membrane microviscosity for glucose uptake in adipose tissue, and (b) leave unclear the mechanism of why dietary fish oil decreases the sensitivity of glucose uptake to insulin in isolated rat adipocytes. PMID- 8352446 TI - Dietary supplementation with N-3 polyunsaturated fatty acids in type 2 diabetes. Effects on glucose homeostasis. PMID- 8352447 TI - Dietary marine fish oils and insulin action in type 2 diabetes. AB - Supplementation of omega-3 fish oils (n-3 FO) usually worsens the glycemic control in type 2 diabetic subjects. This may be a dose-related phenomenon and is reversed after discontinuation of the n-3 FO supplementation. An increase in the daily caloric intake, due to the fat content of n-3 FO supplements, and a consequent weight gain may contribute to the increase in hyperglycemia. Mechanisms of the increase in hyperglycemia include: (1) n-3 FO may interfere with insulin secretion from the pancreas, and this in turn can cause an increase in the hepatic glucose output and/or a decrease in the glucose uptake by the peripheral tissues; (2) n-3 FO may primarily decrease the sensitivity of liver to insulin action and consequently increase gluconeogenesis and/or glycogenolysis and/or decrease the glycogenesis; (3) n-3 FO may primarily affect the sensitivity of peripheral tissues to insulin, resulting in decreased glucose-uptake; (4) n-3 FO may increase the availability of gluconeogenic substrates by directly altering the partitioning of the metabolic fuels for different pathways in the liver. [formula: see text] Direct experimental testing of these possibilities has been difficult, because n-3 FO affects the carbohydrate metabolism differently in animal models than in humans. The available data suggest that n-3 FO inhibits insulin secretion in response to glucose load, mixed meal, and glucagon but not at the fasting state. Hepatic glucose output is increased. Sensitivity of the peripheral tissues to insulin is not changed. An encouraging observation is that the hyperglycemic effect of n-3 FO may decrease with time even when therapy is continued. Proper use of this treatment modality requires careful evaluation of the risk/benefit ratio for every individual patient. PMID- 8352448 TI - Significance of the N-6/N-3 ratio for insulin action in diabetes. AB - This report supplies supportive data for the hypothesis that a high n-6/n-3 dietary fat ratio is a potent, negative variable in NIDDM. Further work is necessary to critically evaluate this hypothesis. PMID- 8352449 TI - Effects of two fat-modified diets on glucose and lipid metabolism in healthy subjects. PMID- 8352450 TI - Effect of a low salt diet on blood pressure and vasoactive hormones in the hereditary hypertriglyceridemic rat. AB - In hereditary HTG rats, basal systolic blood pressure using tail-cuff sphygmomanometry was significantly higher (122.1 +/- 2.1 mm Hg; n = 16) than that in NTG animals (107.1 +/- 1.52; n = 16). A low salt diet did not influence blood pressure in NTG rats during the consecutive 4 weekly periods. However, in the second week blood pressure in HTG rats rose significantly in both the control rats on a normal salt diet and those on a low salt diet (132.5 +/- 1.89, n = 8, and 132.6 +/- 1.93, n = 8). No further changes were registered in the third and fourth week in control HTG rats. On the other hand, blood pressure fell significantly in HTG rats on a low salt diet in the third week in comparison with the second week (119.5 +/- 3.2, n = 8), and it increased again in the fourth week (123.0 +/- 2.35, n = 8). Hormones in plasma were determined at the end of the experiment. Plasma levels of norepinephrine were not influenced by differences in salt intake and were significantly higher by about 45% in HTG than in NTG animals. The lowest concentration of corticosterone in plasma was found in control HTG rats (1.2 +/- 0.2 vs 4.6 +/- 0.8 micrograms/100 ml in control NTG rats). Nevertheless, corticosterone concentration increased in HTG rats on a low salt diet at comparable values found in NTG rats on a low salt diet (3.1 +/- 0.8 vs 4.3 +/- 1.5). Plasma renin activity and plasma aldosterone concentrations were not different in the NTG and HTG groups and were uninfluenced by the diets (Table 1). We conclude that the elevated blood pressure in HTG rats and its variations during the experiment may reflect more pronounced sympathetic activity in HTG rats rather than blood pressure dependency on different salt intake. PMID- 8352451 TI - Insulin resistance and compensatory insulin secretion in middle-aged persons with hypertriglyceridemia. AB - Insulin secretion and insulin sensitivity were measured in hypertriglyceridemic patients using the frequently sampled intravenous glucose tolerance test. Three groups of men who were matched for age and body mass index were studied: eight healthy control subjects (C), seven patients with mild hypertriglyceridemia and normal glucose tolerance (TG), and seven with well-controlled type 2 diabetes with hypertriglyceridemia (TG-DM). The first-phase insulin response was increased by 116% in the TG group and decreased by 59% in the TG-DM group. The second phase of insulin secretion was increased in both TG groups (TG by 310% and TG-DM by 250%). The mean insulin sensitivity index (SI) was reduced by 50% in the TG group and by 60% in the TG-DM group. Glucose effectiveness (SG) was reduced by 30% in the TG-DM group compared with the control subjects. PMID- 8352452 TI - The phenomenon of a high triglyceride response to an oral lipid load in healthy subjects and its link to the metabolic syndrome. AB - Excessive postprandial triglyceride (TG) responses despite normal fasting TG levels have been described in single cases within small groups of healthy subjects and in patients with obesity or precocious atherosclerosis, known to be associated with high insulin fasting levels. To clarify this association, fasting and postprandial TG and insulin levels were studied in 113 healthy young (25.7 +/ 2.6 years), normal weight (body mass index 20.8 +/- 2.3 kg/m2) male subjects who were selected from among 117 subjects on the basis of TG fasting levels < 200 mg/dl. After a 12-hour fast a standardized liquid lipid load was administered containing 58 g mainly saturated fat and 1,017 kcal energy. Both fasting TG values and postprandial TG peak values showed bimodal frequency distributions. Statistical analysis of fasting TG discriminated two groups: a low fasting TG group with normally distributed values < 150 mg/dl (mean +/- SEM: 79.5 +/- 2.7 mg/dl; n = 104) and a high fasting TG group > 150 mg/dl (194.5 +/- 7.2 mg/dl; n = 13). Likewise, two groups could be differentiated according to their maximal postprandial TG response (TG max) to the lipid load: (1) normal responders with TG max < 260 mg/dl (mean +/- SEM: 123 +/- 4.8 mg/dl; n = 96) and (2) high responders with TG max > 260 mg/dl (272.5 +/- 20.5 mg/dl; n = 17). Fasting TG and TG max were highly correlated (r = 0.745; p < 0.0001). However, 9 of 17 (53%) high responders had fasting TG < 150 mg/dl, which means that the prediction of high response is only 47.0% based on fasting TG values. Fasting insulin levels were significantly higher in high responders than in normal responders, whereas they did not differ between the low and high fasting TG group. In conclusion, the bimodal frequency distribution of TG max after a lipid load permitted the differentiation of two groups, normal responders and high responders, with higher fasting insulin levels, which might indicate a link to the metabolic syndrome. PMID- 8352453 TI - Prolonged postprandial increment in triglycerides and decreased postprandial response of very low density lipoproteins in type 2 diabetics following an oral lipid load. PMID- 8352454 TI - Role of N-6 and N-3 fatty acids in the dietary treatment of metabolic disorders. AB - The impetus to examine the effects on n-3 PUFA was generated from epidemiologic studies of a traditional population largely dependent on the marine environment. These studies and clinical interventions support a recommendation to increase the consumption of n-3 fatty acids, particularly in communities that currently have a low n-3 fatty acid intake. If we are to be guided by the diet of other traditional hunter-gatherer populations, dependent on both terrestrial and marine sources of food, it is clear that we may need to reappraise the importance of long chain PUFA of the n-6 series such as arachidonic acid. Recent studies on such populations indicate that elevated arachidonic acid levels, when associated with elevated n-3 PUFA, are likely not to be harmful to health. PMID- 8352455 TI - PUFA supplementation and hypertension in type 1 diabetes. PMID- 8352457 TI - Is it time for a clinical trial of dietary fish oil supplementation in individuals with NIDDM? PMID- 8352456 TI - The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. AB - Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients. PMID- 8352458 TI - Dietary recommendations: what we've learned here. PMID- 8352459 TI - Beneficial effects of a fish oil enriched high lard diet on obesity and hyperlipemia in Zucker rats. PMID- 8352461 TI - Dietary N-3 PUFA-induced changes in heart triglyceride and glucose metabolism of hypertriglyceridemic rats and their relation to insulin action. PMID- 8352460 TI - Dietary fats, fish, and blood pressure. AB - In humans any effects of dietary saturated fats or omega-6 polyunsaturates on blood pressure appear to be mediated by changes in caloric intake and long-term weight changes. In contrast, omega-3 fatty acids have a mild antihypertensive effect which is seen most clearly in untreated subjects with higher blood pressures, in older people, and during sodium restriction. The mechanism may be due to a combination of effects consequent to incorporation of omega-3 fatty acids into vascular phospholipids, leading to reduced formation of endothelial contractile substances in larger vessels and impairment of sympathetic neuroeffector and other vasoconstrictor mechanisms in resistance vessels. PMID- 8352462 TI - Effects of marine fish oil on blood pressure and vascular reactivity in the hereditary hypertriglyceridemic rat. PMID- 8352463 TI - Accumulation of triglycerides in liver following inhibition of fatty acid oxidation by 3-mercaptopropionic acid in perfused liver. PMID- 8352464 TI - Dietary regulation of liver malic enzyme activity in relation to the effect of triiodothyronine. PMID- 8352465 TI - Altered susceptibility to in vitro oxidation of LDL in LDL complexes and LDL aggregates. PMID- 8352466 TI - Effect of feeding arachidonic acid to streptozotocin diabetic rats. PMID- 8352467 TI - Abnormal serum fatty acid composition in non-insulin-dependent diabetes mellitus. PMID- 8352468 TI - Action of dietary polyunsaturated fatty acids on the fluidity of erythrocyte and platelet membrane in NIDDM. PMID- 8352469 TI - Kinetics of free fatty acids in hypertriglyceridemia. Evidence for different types of insulin resistance. PMID- 8352470 TI - Effect of dietary fish oil on the development and regression of atherosclerosis in rabbits. PMID- 8352471 TI - Glucose tolerance, insulin secretion, plasma lipid fatty acids, and the hypolipidemic effects of fish oil. PMID- 8352472 TI - Dietary lipids and glucose tolerance. The San Luis Valley Diabetes Study. PMID- 8352473 TI - Triglyceridemia, glucoregulation, and blood pressure in various rat strains. Effects of dietary carbohydrates. PMID- 8352474 TI - Raised dietary intake of N-3 polyunsaturated fatty acids in high sucrose-induced insulin resistance. Animal studies. PMID- 8352475 TI - High fat diet-induced insulin resistance. Lessons and implications from animal studies. PMID- 8352476 TI - Epidemiologic studies on Eskimos and fish intake. AB - Chronic diseases such as coronary heart disease and diabetes mellitus are uncommon in Eskimos. Total cholesterol levels are generally low, whereas HDL cholesterol levels are higher than those in an age- and sex-matched Danish population. It is frequently assumed that this is mainly due to their dietary pattern, especially with its high content of n-3 polyunsaturated fatty acids, derived from fish and other seafoods. Dietary surveys have shown that the intake of n-3 polyunsaturated fatty acids in Eskimos is about 14 g/day, whereas it is 3 g/day in Denmark and about 0.2 g/day in the United States. However, the Eskimo diet also differs from the Western diet in other aspects, especially in the intake of saturated fatty acids which is low (9 energy-%). The intake of dietary cholesterol is rather high because of the large consumption of seafood. Individually based studies are better suited to disentangle the health effects of different nutrients, inasmuch as confounding factors can be taken into account. Several cohort studies have now shown that the consumption of 1-2 fish meals per week is associated with a reduction in the risk of coronary heart disease. Recently, similar results concerning glucose intolerance and stroke were also reported. These combined data suggest that a diet low in saturated fatty acids, in combination with a low or moderate level of fish consumption, may be of importance in the prevention of diseases such as coronary heart disease, ischemic stroke, and diabetes mellitus. PMID- 8352477 TI - Insulin resistance in high fat fed rats. Role of glucose transporters, membrane lipids, and triglyceride stores. PMID- 8352478 TI - Fish oil in a high lard diet prevents obesity, hyperlipemia, and adipocyte insulin resistance in rats. PMID- 8352479 TI - Thyroplasty: a new approach. AB - A new type of thyroplasty implant (prosthesis) has been designed to be used of a surgical operation that accomplishes medial displacement of a paralyzed vocal cord. The implant is inserted through a rectangular window fashioned in the thyroid lamina on the side of the vocal cord paralysis. Instruments for measuring the location and outline of the window in the thyroid lamina are presented. A thyroplasty saw blade is introduced. By using this blade, a window of precise measurement can be constructed without injury to the underlying perichondrium. The implant is constructed from a biocompatible, medical-grade polymer. Four sizes each are available for the male and female larynges. The proper-size implant can be selected with a measuring device. It is not necessary to alter the implant at the time of surgery; it snaps into place and suturing is not necessary. Once the implant is inserted, its medial or lateral displacement is not possible; on the other hand, the implant can be easily removed if vocal cord function returns, or if a change to a different-size implant is indicated. The design of the implant will close the posterior commissure. PMID- 8352480 TI - Measurement of Young's modulus in the in vivo human vocal folds. AB - Currently, surgeons have no objective means to evaluate and optimize results of phonosurgery intraoperatively. Instead, they usually judge the vocal folds subjectively by visual inspection or by listening to the voice. This paper describes a new device that measures Young's (elastic) modulus values for the human vocal fold intraoperatively. Physiologically, the modulus of the vocal fold may be important in determining the nature of vocal fold vibration in normal and pathologic states. This study also reports the effect of recurrent laryngeal nerve stimulation on Young's modulus of the human vocal folds, measured by means of transcutaneous nerve stimulation techniques. Young's modulus increased with increases in current stimulation to the recurrent laryngeal nerve. Ultimately, Young's modulus values may assist surgeons in optimizing the results of various phonosurgeries. PMID- 8352482 TI - Experimental endolymphatic hydrops and glycerol. Electrophysiologic study. AB - The object of the present study was to evaluate electrophysiologically the therapeutic effect of glycerol on the cochlear function of guinea pigs in which experimental hydrops had been surgically induced. Fifteen albino guinea pigs were used. Each animal was chronically implanted to follow the evolution of hearing. The experimental protocol considered 3 groups of guinea pigs (5 animals each). Group 1 received no drug treatment, while groups 2 and 3 were given glycerol orally at 0.75 and 0.50 g/kg of body weight once a day for 4 months. The audiograms of the animals treated with glycerol showed a statistically significant hearing improvement compared with the control group. Clinically, our results seem to support the view of those who favor the use of glycerol for the medical treatment of Meniere's disease at an early stage. PMID- 8352481 TI - Carcinoma in situ of the glottis: radiotherapy or excision biopsy? AB - Excision biopsy, radiotherapy, and laryngofissure cordectomy have all been used, but the best treatment regimen for glottic carcinoma in situ remains controversial. A 20-year experience of 37 cases is reported. For the first 10 years biopsy with radiotherapy was the first-line treatment (n = 20), but for the last 10 years surgical or laser excision biopsy alone has been performed (n = 17). The T stage of the carcinoma in situ does not determine its premalignant potential. Malignancy appears to be a recurrence, rather than a new expression of carcinogenesis. Excision biopsy alone provides local control results (75%) comparable to those of primary radiotherapy (85%). Excision biopsy alone, however, retains the option of subsequent radiotherapy with preservation of laryngeal function, but very close follow-up, especially in the first year, is required. PMID- 8352483 TI - Experimental otitis media with effusion induced by platelet activating factor. AB - This study tested the hypothesis that platelet activating factor (PAF) in the middle ear can induce otitis media with effusion (OME) and that PAF antagonists can prevent PAF-induced OME. An initial trial of 16 micrograms of PAF was injected into chinchilla bullae, and all ears developed middle ear effusion (MEE) within 48 hours. Subsequent trials were performed to test dose dependency. Interestingly, 1 or 16 micrograms of PAF caused more MEE and inflammation than did 4 or 8 micrograms. A dose of 0.5 micrograms PAF did not cause MEE. Middle ear effusion from injected bullae contained the full spectrum of lipoxygenase and cyclooxygenase products; additionally, more PAF was detected than was injected. Finally, a PAF antagonist (WEB 2170) injected intraperitoneally prevented PAF induced OME. This study demonstrates that PAF injected into the middle ear can induce OME and that PAF antagonists effectively prevent PAF-induced OME. These findings suggest that PAF plays an important role in the pathogenesis of OME. PMID- 8352484 TI - Classification of congenital middle ear anomalies. Report on 144 ears. AB - The surgical findings in 144 successive ears operated on for congenital conductive hearing loss were analyzed, and the results were evaluated in terms of hearing gain. All the patients underwent middle ear surgery at the University Hospital Nijmegen between 1964 and 1990. A classification system was developed to analyze the findings. Class 1 comprises ears with congenital isolated stapes ankylosis. Class 2 comprises ears with congenital stapes ankylosis in combination with a congenital anomaly of the ossicular chain. Class 3 comprises ears with congenital anomalies of the ossicular chain and at least a mobile stapes footplate. Class 4 comprises ears with aplasia or severe dysplasia of the oval window or round window. PMID- 8352485 TI - Australian experience with functional endoscopic sinus surgery and its complications. AB - There have been reports of severe complications from functional endoscopic sinus surgery; however, it is unclear as to how the rate compares with that of the more traditional forms of intranasal surgery. To ascertain this, I circulated a questionnaire to 100 otolaryngologists in Australia known to have an interest in endoscopic nasal surgery and analyzed the results. The results of this survey show that complications are very infrequent and that the rates for functional endoscopic sinus surgery compare favorably with those of the traditional techniques. PMID- 8352486 TI - Differential osteoclast activation in endochondral and intramembranous bone. AB - Osteoclast activation within the temporal bone leads to hearing loss in a variety of pathologic conditions, including otosclerosis, osteogenesis imperfecta, Paget's disease of bone, and chronic otitis media. Although endochondral (EC) bone is remodeled in these diseases, it is relatively more resistant to remodeling when compared to intramembranous (IM) bone. In this study, localized bone resorption and remodeling were induced on the inner surface of the middle ear by pressurization with air to 10 mm Hg above atmospheric. Osteoclast surface increased in IM bone, but not in EC bone. This study supports the concept that there may be fundamental differences between EC and IM bone and that EC is more resistant to pressure-induced localized resorption than IM bone. PMID- 8352487 TI - Congenital ankyloglossia with deviation of the epiglottis and larynx: symptoms and respiratory function in adults. AB - We operated on 38 adult patients with congenital ankyloglossia with deviation of the epiglottis and larynx. The results were as follows. 1) Most patients had Angle's class III malocclusion, irregular alignment of the upper teeth, and high hard palate. 2) Fifty percent of the patients in our study population had obstructive respiratory failure. Their vital capacity increased significantly after the operation, but changes of forced expiratory volume in 1 second were not prominent. 3) Subjective symptoms of this disease were stiffness of the shoulders, a cold feeling in the extremities, an obstructed feeling in the throat, insomnia, fatigue, dry skin, irritability and/or anxiety, and nervousness. These improved postoperatively. 4) Objective symptoms included snoring, muscle cramps, difficulty in playing wind instruments, hoarseness, and incorrect articulation. The objective symptoms, except for incorrect articulation, improved postoperatively. PMID- 8352488 TI - Morphology of the membrana limitans. AB - The morphology of the membrana limitans (ML) was studied by light and electron microscopy to further understand its functional significance. The ML is a porous shield composed of a few to several layers of tightly packed fibrocytes that separate the perilymphatic space of the cochlea and saccule from that of the utricle and canal system. These fibrocytes are thinner on the side of the vestibule. They show many desmosomes and gap junctions and are interspersed with fibrils. The 3-dimensional reconstruction from celloidin sections shows that the ML, as it is viewed from the anterior side, is rectangular in shape, with various surface curvatures and an invagination toward the internal aperture of the vestibular aqueduct. Horseradish peroxidase, a tracer substance, placed on either side of the ML fails to pass to the opposite side. The ML and trabecular meshwork may be a factor contributing to differential sensitivity of cochlear and vestibular sensory cells in the presence of noxious substances. PMID- 8352489 TI - Sources of variability in posterior rhinomanometry. AB - Sources of variability in nasal airway resistance measured by posterior rhinomanometry were studied in 5 subjects tested on 5 different days and 56 subjects tested on 2 different days. On each day, a questionnaire on upper airway health and nasal symptoms was completed. The mean individual difference in nasal airway resistance between the 2 test days in the group of 56 subjects was 5.3% (SD 52.7%). Between-subject variability accounted for 74.9% and 72.5% of the total variability in the group of 5 and the group of 56 subjects, respectively. For the 5 subjects, by accounting for a change in upper airway symptoms or upper respiratory tract infection that occurred over the 5 test days, there was a significant decrease in the between-subject variability. The difference in sources of variation due to a change in upper airway symptoms was not seen in the group of 56 subjects. We conclude that the largest source of variability in nasal airway resistance is due to between-subject differences. PMID- 8352490 TI - Mucosal fine structure in experimental sinusitis. AB - Rabbit maxillary sinuses were inoculated with Streptococcus pneumoniae and Bacteroides fragilis, and the histologic response in the sinus mucosa was observed over a 12-week period. An increased height of the cylindric cells and hyperplasia of the basal cells were frequent findings irrespective of the pathogen inoculated. The disease was found to influence the character of the secretory product from epithelial secretory cells and to degranulate the subepithelial glands. Ciliary loss was a transitional finding. A reduction in the number of mitochondria, the occurrence of deformed short microvilli, and cytoplasmic blebbing were seen in the cells devoid of normal cilia. It is inferred from this study that pneumococcal sinusitis in rabbits is a self limiting process, and the mucosal sequelae of the acute infection are persisting goblet cells, slight focal fibrosis, and edema. Inoculation with B fragilis produces a chronic inflammatory process, with infiltration of mononuclear cells, luminal dilatation of the glands exhibiting zymogen granule depletion, and an increased thickness of the whole mucosal layer. PMID- 8352491 TI - Giant congenital cholesteatoma. PMID- 8352492 TI - Papillary neoplasms (Heffner's tumors) of the endolymphatic sac. AB - The sources of adenomatous neoplasms in the temporal bones are usually metastases or direct extensions from extratemporal lesions, or primary from the middle ear cleft. In 1989, Heffner added the endolymphatic sac's epithelium as another possible generative origin. In contrast to the adenomatous tumors of the middle ear or mastoid, the papillary cystic neoplasms of the endolymphatic sac are large and locally aggressive and often involve the middle and posterior cranial fossae and bone. These biologically low-grade adenocarcinomas have not been shown to be able to metastasize. PMID- 8352493 TI - Impact of the acquired immunodeficiency syndrome epidemic on the practice of laryngology. AB - In only 10 years, the acquired immunodeficiency syndrome epidemic has already had an enormous impact on many aspects of the practice of medicine. The practice of laryngology typifies the changes that have occurred. Heightened clinical vigilance has been required as the laryngologist encounters new and unusual manifestations of the disease and must take more extensive histories regarding social, behavioral, and sexual practices than were previously necessary. The performance of physical examinations and surgical procedures has also changed as a result of experience with the lethal human immunodeficiency virus. Numerous legal, ethical, and social issues have also been raised by the epidemic and have had a major influence on how medicine is practiced and regulated. In this paper we review the laryngeal and pharyngeal manifestations of acquired immunodeficiency syndrome and discuss illustrative patient examples that demonstrate the impact of the disease. We also consider the diverse groups of issues that attend this epidemic and that continue to modify practice patterns. PMID- 8352494 TI - [Treatment of hyperthyroidism in children with antithyroid drugs]. AB - Sixteen cases of pediatric hyperthyroidism treated by antithyroid drugs are reported. First-line treatment with carbimazole in a mean dose of 19 mg/m2 initially and 7 mg/m2 after one year ensured control of the disease within 6 weeks. Mean follow-up was 4 years. Only two children were able to discontinue the drug, after 9.1 years and 4.6 years. Two other patients had thyroidectomy, after 6.7 years and 3.4 years. The main disadvantages of antithyroid drugs are the need for prolonged treatment and the risk of recurrence. An attempt at treatment discontinuation is warranted in patients with good disease control of 2 to 3 years duration, goiter size reduction, improved exophthalmos, and decreased anti TSH receptor antibodies. PMID- 8352495 TI - [Deficiencies of physiological coagulation inhibitors in children with venous thromboses of the lower limbs. Prospective study of 6 cases]. AB - Six patients aged 3 to 14 years with lower limb vein thrombosis were included in a prospective study of deficiencies in physiological coagulation inhibitors. The laboratory evaluation included standard hemostasis tests, tests for circulating anticoagulants, immunological and functional assays of protein C, protein S, and antithrombin III, and a study of fibrinolysis. A qualitative protein S deficiency with decreased fibrinolysis and protein C deficiency were found. The family study detected asymptomatic heterozygotes in both families investigated. No antithrombin III deficiency or circulating anticoagulants were found. PMID- 8352496 TI - [Clinical experience with totally implantable venous access systems in pediatric hematology and oncology]. AB - Forty-three children with malignant diseases who received 48 totally implanted venous accesses (TIVA) were retrospectively analyzed. More than half the patients had acute leukemia. Mean age was 6 years 10 months. Mean duration of use of the TIVA was 473 +/- 50 days (range 28 to 1,285 da; median 424 days). Removal of the TIVA was required because of an adverse event in 33% of cases. Main reasons for removal included infection (22.9%), thrombosis (6.25%), and catheter dysfunction (4.16%). Catheter-related infections were most often due to staphylococci (90%), especially S. epidermidis (63%). Infection rate was 0.48 per 1,000 patient-days. Flushing with a vancomycin-heparin solution can be expected to decrease this rate. Selection of the implantation site is discussed. In children under 6 years of age, the cephalic vein and external jugular vein are often frail or absent and are therefore less appropriate than the internal jugular vein or subclavian vein. PMID- 8352497 TI - [Value of flexible fiberoptic bronchoscopy under local anesthesia in infants]. AB - From October 1991 through April 1992, 16 infants aged 5 to 25 months (mean age 14.3 months) underwent bronchoscopy with a flexible fiberoptic bronchoscope, under local anesthesia. The technique is described in detail. Reasons for bronchoscopy included recurrent or persistent pneumonia (n = 4), persistent atelectasia (n = 4), lymphadenopathy and/or airway compression (n = 2), suspected foreign body (n = 2), bronchoalveolar lavage to investigate diffuse interstitial lung disease (n = 2), and severe recurrent wheezing (n = 2). The procedure established the accurate diagnosis in 14 cases. Adverse events (32%) were minor (transient hypoxia, n = 3; moderate fever, n = 1; and laryngospasm, n = 1) and resolved completely. Flexible fiberoptic bronchoscopy under local anesthesia is a simple procedure which is safe in patients under 30 months of age when performed by a experienced operator in an adequate facility. This method is useful for the diagnosis and/or treatment of a broad spectrum of conditions. PMID- 8352498 TI - [Helicobacter pylori gastritis manifested by acute anemia]. AB - Helicobacter pylori gastritis usually manifests as recurrent abdominal pain but is sometimes discovered upon evaluation for digestive tract bleeding with severe anemia. An 11-year-old who was not under medication and had no history of pain was admitted for isolated regenerative anemia (5.6 g/dl) due to digestive tract bleeding. Laboratory tests showed only low serum iron and ferritin levels. Endoscopy disclosed hemorrhagic inflammation of the duodenal cap and antritis with a hillocky appearance. The diagnosis of H. pylori infection was established on the basis of the finding of curved Gram-negative rods on the smears and of a positive urea test. There was moderate interstitial antritis. The patient was given an H2 antagonist (ranitidine) and amoxicillin with tinidazole for six weeks. Serum IgG antibodies against H. pylori were found in the child's parents and siblings, with the exception of a 7 month old infant. A ten year old sister had been hospitalized two years earlier for hemorrhagic duodenitis ascribed at the time to use of acetylsalicylic acid. H. pylori has been reported in 40% to 95% of pediatric patients with primary gastritis. Physicians should be familiar with this frequent, often familial disease. Management rests on concomitant administration of two antimicrobials and an acid secretion inhibitor to the index patient and family members. Endoscopy is too invasive to be appropriate for monitoring the outcome. In practice, recovery is affirmed on the basis of resolution of clinical manifestations and decreased levels of anti-H. pylori antibodies. PMID- 8352499 TI - [Apple-peel jejunal atresia. Nutritional management]. AB - Apple-peel jejunal atresia is a rare digestive tract congenital defect often accompanied with a short gut. Two cases managed by a three-stage medical and surgical approach are reported. A protein hydrolysate-jejunal secretion mixture was drip-fed through the distal ileostomy to stimulate trophicity of the distal gut. PMID- 8352500 TI - [Histiocytic proliferative diseases. Discussion of a case report]. AB - The case of a ten month old female with initial clinical and histological findings suggestive of inappropriate macrophage activation syndrome is reported. Subsequently, clinical and pathological changes refuted this diagnosis and demonstrated that the patient had Langherans cell histiocytosis. Clinical, laboratory and pathological findings characteristic of each type of histiocytosis are reviewed. Histological and immunohistochemical studies allow to establish the diagnosis of Langherans cell histiocytosis. The finding of erythrophagocytosis in our patient suggests that two types of histiocyte proliferation can coexist in the same individual. PMID- 8352501 TI - [Association of Moebius syndrome and hypopituitarism due to a midline anomaly. A case report]. AB - A 14 year old patient had both Moebius anomalad with arthrogryposis and growth hormone deficiency due to a midline defect. This combination suggests an abnormality in the organization of the neural crest and homologous neural tube segment. PMID- 8352502 TI - [Multiple finger geodes in children]. AB - Three pediatric patients with multiple geodes in the fingers are reported. This condition occurs mainly between one and three years and at seven years of age and is more common in winter. Affected fingers are swollen. Roentgenograms disclose several small lucent defects which are usually located in the middle phalanx. Several fingers are usually involved. The erythrocyte sedimentation rate is increased in virtually every case. Resolution occurs spontaneously within a few weeks or months. There is no tendency towards recurrence. Although the condition is inflammatory, exposure to cold is probably a precipitating factor. PMID- 8352503 TI - [It doesn't only happen to others: medical expertise]. PMID- 8352504 TI - [Adjuvant treatments in resectable cancer of the rectum: preoperative radiotherapy, postoperative radiation- and chemotherapy or nothing?]. AB - In addition to curative surgical resection, which remains the treatment of choice in rectal cancer, are there any other effective adjuvant treatments capable of increasing the life expectancy of patients by decreasing the frequency of local recurrences and distant metastases? Analysis of the results and clinical arguments in favour of adjuvant treatments demonstrates the efficacy of preoperative radiotherapy which decreases the pelvic recurrence rate in patients with T2T3T4NxM0 tumours. Postoperative administration of a combination of radiotherapy and chemotherapy (5-FU, methyl CCNU) also improved the survival rate and disease-free interval in patients operated for rectal cancer. However, the adverse effects and toxicity of this adjuvant treatment limit its routine administration. Lastly, the efficacy of postoperative radiotherapy and postoperative chemotherapy, administered separately, has not been clearly demonstrated to date. PMID- 8352505 TI - [Treatment of sclerodermic esophagitis: value of duodenal diversion]. AB - Between 1985 and 1990, six patients were operated on using duodenal diversion for reflux esophagitis with scleroderma. Duodenal diversion was performed twice as initial procedure and 4 times as treatment of unsuccessful antireflux procedure performed ten years previously. Duodenal diversion was associated with truncal vagotomy. In cases of reoperation the initial reconstruction procedure was removed. An esophageal stricture was resected in one case. One patient with previous truncal vagotomy and pyloroplasty underwent supra papillary diversion. There was no postoperative death. The mean follow-up was 28 months with one patient lost to follow-up. For 4 patients, the postoperative weight gain was 10 per cent. Abnormalities of lower esophageal motility in scleroderma account for the poor results after classical antireflux procedures. In these cases duodenal diversion is indicated as primary treatment. In cases of reoperation removal of the initial anti-reflux device is required in association with duodenal diversion. PMID- 8352506 TI - [Cholecystectomy by celioscopy. Apropos of 126 cases]. AB - One hundred twenty-six cases who underwent laparoscopic cholecystectomy were included in the study: 28 males and 98 females with a mean age of 44.2 years. Laparoscopic cholecystectomy was performed for uncomplicated cholelithiasis (111 cases), acute cholecystitis (10 cases), biliary pancreatitis (2 cases) and cholangitis (3 cases). The mean operative time was 78 minutes. In 7 cases, a transformation into open surgery was necessary (5.5%). There were no deaths and one major complication was reported: an iatrogenic injury to the bile duct requiring secondary laparotomy. The mean hospital stay was 3.4 days. However, despite several advantages, this new technique must be performed by a surgeon with experience of biliary tract surgery. PMID- 8352507 TI - [Celioscopic gastrostomies and jejunostomies]. AB - The authors describe a technique of laparoscopic gastrostomy and jejunostomy, which has been used in 23 patients between May 1991 and August 1992: 13 laparoscopic gastrostomies (LG) and 10 laparoscopic jejunostomies (LJ), all performed under general anaesthesia. There were no operative deaths, one intraoperative complication and 3 postoperative complications. Twelve patients had died by the end of the study, 7 patients were still using their feeding tube and 4 patients ate normally. The mean duration of use of the feeding tubes was 4 months for LG and 43 days for LJ. The secondary complications consisted of 3 tube obstructions and one case of pyloric obstruction. Laparoscopic gastrostomy and jejunostomy, performed according to the method described, constitute an effective and reliable alternative to open operations. They can be performed in cases in which endoscopic gastrostomy is impossible. Due to its technical simplicity, laparoscopic jejunostomy should be preferred to gastrostomy whenever there is a risk of inhalation. PMID- 8352508 TI - [Right iliac fossa pain in women. Conventional diagnostic approach versus primary laparoscopy. A controlled study (65 cases)]. AB - In a series of 187 patients with acute abdominal pain syndrome, 65 young women reported non specific pain in right iliac or pelvic area. A controlled study compared 33 patients with immediate laparoscopy and 32 explored with a laboratory contrast or imaging approach. In the laparoscopic group, an exact diagnosis was made in 97% of the patients, allowing in 2/3 of cases the endoscopic treatment. Only 28% in the second group had an exact diagnosis. Hospital stay was shorter in the laparoscopic group (4.18 vs 6.16 days; p = 0.01) decreasing the hospital cost. The authors suggest that immediate laparoscopy should be performed in young women presenting with non-specific abdominal pain. PMID- 8352509 TI - [Negative emergency laparotomies 1950-1989]. AB - In order to list the negative emergency laparotomies, the records of 24,494 laparotomies performed from 1950 to 1989 were examined. 211 negative laparotomies were performed over this 40 years period: 49 for abdominal trauma, 42 for supposed intestinal obstruction, 44 for supposed peritonitis or visceral infection, 46 for presumed early post-operative abdominal complications and 30 for gastrointestinal bleeding. Over these 4 decades, the emergency laparotomy rate and negative laparotomy rate remained stable despite changes in the diagnostic tools, in the age of the patients and the frequency of their diseases. PMID- 8352510 TI - [Surgical treatment of supralevator rectocele. Value of transanal excision with automatic stapler and linear suture clips]. AB - A retrospective review of 20 rectoceles performed over a four year period (1988 1991) was carried out. The major indication for repair was constipation and outlet obstruction. All patients were objectively quantified by standardized defecography and functional investigations. All patients were repaired via a trans-anal approach using a linear stapler. Sixteen patients were improved with a mean follow-up of 21.8 months. PMID- 8352511 TI - [Is there still a place for surgery in the treatment of communicating pseudocyst in chronic pancreatitis?]. AB - The purpose of this study was to evaluate the results of long term percutaneous catheter drainage in the treatment of chronic pancreatic pseudocysts communicating with pancreatic ducts. Since 1986, 13 consecutive patients with symptomatic pseudocysts were treated prospectively. All pseudocysts were associated with chronic pancreatitis. The location was head (n = 8), body (n = 3) or tail (n = 2). The procedure included fine needle aspiration under ultrasonic control, percutaneous drainage along a guide wire and closed suction aspiration. A radiological control was performed weekly and the catheter was left in place until total resolution of pseudocyst. Immediate relief of pain and resolution of pseudocyst were obtained in all 13 patients. The average length of hospital stay was 12.2 +/- 8 days (1 to 23). The average duration of drainage was 36 days. There was no mortality of morbidity related to the drainage. There were two asymptomatic recurrences, but long-term follow-up (mean 3 years) showed that all 13 patients were symptom-free. The clinical results of such a long-term catheter drainage seem better in our study than in other previous series. It is a simple and innocuous procedure, and could be carried out in an outpatient unit. Such drainage represents an efficient alternative to endoscopic or surgical treatment of chronic pancreatic pseudocyst with ductal communication. In our experience surgery is no longer indicated. PMID- 8352512 TI - [Intestinal metastases from breast cancer. Apropos of 8 cases]. AB - Eight patients with intestinal metastases from breast cancer are described. The different clinical presentations and pathological types are studied. The difficulty in distinguishing such uncommon secondary sites of breast cancer from primary intestinal cancer is emphasized. Attention should be paid to intestinal symptoms in women with a history of infiltrating lobular breast cancer: in agreement with recent literature data the lobular type seems mainly responsible for gastrointestinal and peritoneal involvement originating from breast cancer (7 cases out of 8 in our series). Prolonged survival could be obtained if no metastases elsewhere were found with appropriate treatment including ablative surgery, chemotherapy and hormonotherapy. PMID- 8352513 TI - [Metatarsalgia and modified Helal's operation. Apropos of a series of 40 cases]. AB - The authors report a series of 40 cases of metatarsalgia operated according to a modified Helal technique. The mid-diaphyseal osteotomy was situated obliquely inferoanteriorly at an angle of 45 degrees on the metatarsal diaphysis. Twenty cases of hallux valgus were operated during the same procedure Surgery allowed a reduction in pain and hyperkeratosis in 67.5% of patients. Comparison of the results obtained with those reported in the literature confirms that the osteotomy must be metaphyseal and that weight bearing must be early and effective. PMID- 8352514 TI - [Desmoid tumors or intra-abdominal fibromatoses]. AB - Intraabdominal desmoid tumour or fibromatosis, recurrent but non-metastatic, invasive, fibroblastic proliferations, are rare tumours. From 1968 to 1989, 16 patients were treated at Gustave Roussy Institute. They were associated with familial adenomatous polyposis in 10% of cases. These tumours, observed mainly in young women (70 to 85% of cases), are aggravated by pregnancy, and spontaneous regression can occur at menopause, proving their hormonal dependence. Although histologically benign, they are serious lesions due to their invasive character; their excision is complete in only 50% of cases. They recur in 30% to 75% of cases and cause death of the patient in 30% of cases. Treatment is surgical but due to their often very slow course, and their spontaneous stabilisation in some cases, a mutilating surgical treatment (extensive small intestine resection) does not seem to be justified. Radiotherapy is effective only at doses incompatible with the site of these tumours (35 to 60 Gy). Chemotherapy has never been shown to be effective. PMID- 8352515 TI - [How to choose a camera and a light source for endoscopy?]. PMID- 8352516 TI - [Nephrocutaneous fistula revealing xanthogranulomatous pyelonephritis]. AB - A patient presented with a reno-cutaneous fistula revealing a xanthogranulomatous pyelonephritis secondary to staghorn calculus. Total nephrectomy was necessary because of renal destruction. This treatment allowed closure of the fistula and a good clinical result. PMID- 8352517 TI - [Efficacy and tolerance of imipenem/cilastatin in the adjuvant treatment of surgery for peritonitis in patients over the age of 70 years]. AB - Eighty eight patients over the age of 70 years, suffering from peritonitis, were treated with imipenem/cilastatin single-agent therapy as a complement to surgery. The recommended dosage was 30 mg/kg/day and could be increased up to 50 mg/kg/day, without exceeding four grams per day, administered by four infusions per day. Seventy three patients (32 males, 41 females) with a mean, age of eighty years and suffering from peritonitis due to perforation, were evaluated. One half of patients presented one or several risk factors on inclusion into the study, one third received ventilatory assistance and 28.5% presented with shock. The perforation was situated in the stomach and duodenum (N = 24), biliary tract (N = 8), small intestine (N = 3), caecum (N = 10) and colon or sigmoid (N = 28). The infection was polymicrobial in 57.4% of cases. Blood cultures were positive in seven patients and cultures remained sterile in seven patients. A clinical success was obtained in sixty four patients (87%): fifty-six patients were cured and eight were improved. Six patients died as a result of infection (mortality: 8.2%) and three were not improved. No failure was due to development of an imipenem-resistant organism. These results confirm the efficacy of imipenem/cilastatin single-agent therapy as a complement to surgery for severe intra-abdominal infections in this high-risk elderly population. PMID- 8352518 TI - Stimulation of iodination and cytokine production by dehydrogenation polymers of phenylpropenoids. AB - Dehydrogenation polymers of phenylpropenoids (so-called 'synthetic lignins') stimulated the iodination (incorporation of radioactive iodine into an acid insoluble fraction) of human peripheral blood monocytes and polymorphonuclear cells (PMN). The stimulation activity of the polymers strongly depended on the amount of hydrogen peroxide used during sample preparation, and on the temperature during iodination assay. These polymers also stimulated the production of interleukin-1 and tumor necrosis factor by peripheral blood mononuclear cells. On the other hand, neither iodination nor cytokine production was significantly affected by the phenylpropenoid monomers. Although the polymers stimulated the iodination of human leukemic cell lines (HL-60, ML-1), they did not induce cytokine production in these cells. The results suggest that stimulation of iodination and cytokine production by dehydrogenation polymers of phenylpropenoids might be regulated differently. PMID- 8352519 TI - Effects of some ruthenium chelates on MCa mammary carcinoma and on TLX5 lymphoma in mice. AB - A group of four Ruthenium chelates of the mixed hard/soft N-S donor ligands 2 formylpyridine (4-H/4-phenyl)thiosemicarbazone has been studied in the experimental models of MCa mammary carcinoma and TLX5 lymphoma in the CBA mouse. Although all the four tested complexes, bis-[2-formylpyridine(4- phenyl)thiosemicarbazone]ruthenium(II)chloride]Ru(L1)(L1H)Cl, 1], [2 formylpyridine(4-phenyl)thiosemicarbazone]ruthenium(II)-mu- trichloro chloro(imidazole)ruthenium(III)monomethanolate [Ru2(L1)(imz)Cl4.CH3OH, 9]. [2 formylpyridine(4-phenyl)thiosemicarbazone]dichloroimidazoler uthenium(II) [Ru(L1H)(imz)Cl2,10] and bis[2- formylpyridinethiosemicarbazone]ruthenium(II) perchlorate, dihydrate [Ru(L)(LH)ClO4.2H2O, 16], reduced the formation of lung metastases at the same extent only compound 1 caused parallel inhibition of the growth of the primary tumor. The chemical nature of the tested compounds seems to determine the nature of the antitumor effects and the bis-chelates are found to be endowed with greater cytotoxic properties towards primary tumor than the monochelates. This opens up a very interesting point, whether it is the presence of two chelate rings around the Ruthenium(II)/(III) acceptor centre or the increase in the number of the soft (S) donor centers that generates greater cytotoxic properties in the corresponding ruthenium complexes. As far as the reduction of the metastasis formation is concerned, it appears that among the four Ruthenium chelates tested, it is possible to identify structures capable of controlling the spread of tumor to the lungs in the absence of significant cytotoxicity for tumor cells. This finding appears of importance in that it indicates the possibility of a specific mechanism of interaction with cells of the metastatic tumor. In this context it appears necessary to investigate other congeners of this "family" with more sulfur donor sites and particularly those with better water solubility. PMID- 8352520 TI - Diverse biological activities displayed by phenothiazines, benzo[a]phenothiazines and benz[c]acridins (review). AB - This review summarizes our experiments which are investigating the relationship between the structure and activity of mainly phenothiazines, benzo[a]phenothiazines and benz[c]acridines. Phenothiazines had potent antiplasmid and antibacterial activities, but induced weak antimicrobial activity in vivo. Their antiplasmid activity seemed to be enhanced by Cl- or CF3- substitution at the 2C position of phenothiazines and modified by the side-chain length and hydrophobicity. Benzo[a]phenothiazines did not show any significant antiplasmid or antibacterial activity, but stimulated the differentiation of human myelogenous leukemic cell lines and natural killing activity of human peripheral blood mononuclear cells in vitro, and induced antimicrobial activity in vivo. Circuit current energy (CRE), circuit current (CC), bond current (BC), diatropic and paratropic properties of benzo[a]phenothiazines might be correlated with their biological activity. Benz[a]acridine showed both in vitro and in vivo antimicrobial activities, and carcinogenic activity for skin tumor. The carcinogenic benz[c]acridines showed out-of-phase in the L-region and their energy was accumulated in the K-region of the molecular orbitals. The results suggest the involvement of different molecular orbitals for the expression of various biological activities by phenothiazines, benzo[a]phenothiazines and benz[c]acridines. PMID- 8352521 TI - Polyamine deprivation stimulates natural killer cell activity in cancerous mice. AB - It has recently been established that the total blockade of all endogenous and exogenous sources of polyamines by a drug containing polyamine deficient chow (DC PDC+) could inhibit tumor growth in vivo and increase the antitumoral efficacy of chemotherapy drugs. We show here that polyamine deprivation obtained with DC-PDC+ not only influences tumor development via reduction of polyamine concentrations in the tumor itself but, in addition, stimulates cells of the non-specific immune system specialized in tumor cell killing. We report that mice grafted with the 3LL carcinoma present a dramatic decrease in the cytotoxic activity of their natural killer (NK) cells. When these animals are treated with DC-PDC+, their NK cell activity is completely restored to normal values. Normalization of leucocyte number and differential count was observed as well. With respect to the different components of the DC-PDC+, it was observed that the endogenous and exogenous sources of polyamines have a different degree of impact on tumor development. For example, when only polyamines from digestive sources are deprived, a weak but significant improvement in NK activity and antitumoral effects were observed, without affecting intra-tumoral polyamine concentrations. We conclude that polyamines, secreted by the tumor itself as well as absorbed through the gastrointestinal tract, could now be considered not only as autocrine growth factors but also as natural immunosuppressive factors. PMID- 8352522 TI - The interference of geographical changes of cancer risk in tumor etiology in Japan. AB - An attempt was made to elucidate the relation between various human neoplasias in their geneses by comparatively investigating the geographical changes of cancer risk either between 2 sexes with one neoplasia or between two neoplasias for each sex with the data of multiple local populations of Japan as well as of the world. Specific cancer death rates for 11 sites in 46 prefectures of Japan, 1969-1971, were used in the domestic study, and age-adjusted cancer incidence rates for the corresponding 11 sites in 40 selected cancer registration areas of the world were used in the international study. The relation between 2 cancer risks was analyzed by calculating a 1st order regression equation using log-transformed data sets. Results obtained are as follows: 1) both the domestic and international data sets confirmed positive correlations of a high degree between the male and the female cancer risks in 6 out of 7 cancer sites tested (esophagus, stomach, colon, rectum, liver and bladder). A positive intersex correlation was also observed in lung cancer with the international data, but not with the domestic one. It was indicated that the male and female populations of Japan as well as of the world were under the influence of a common risk modifier in the course of geographical changes of cancer risk for each of 6 neoplasias except lung cancer. 2) Intercancer correlation was lacking in 11 out of 23 cancer pairs in the domestic study, whereas all 22 intercancer correlations but one in the international study were found to be statistically significant. Further insight into the correlation data of the international study led to the conclusion that the observed combination of positive and negative correlation in the 22 cancer pairs were explainable in terms of the differential cancer risk changes of Western type and Non-Western type cancers due to the transition of life style between the Western extreme and the Non-Western extreme in the world. In contrast, a high proportion of non-correlations (11 out of 23 cancer pairs) and emergence of opposite or new correlations (3 out of 23 pairs) were observed in the domestic study, a finding which indicates that the domestic cancer risk modifier, as evidenced in the intersex correlation test, is site-specific, and is to be differentiated from the Westernization-sensitive cancer risk modifiers of the international study.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8352524 TI - Differentiation of promyelocytic leukemia cells HL-60 induced by daidzein in vitro and in vivo. AB - We have screened more than one thousand synthetic and natural chemicals to explore differentiation inducers and found that daidzein has potent differentiation-inducing activity for human leukemia HL-60 cells, both in vitro and in vivo. In vitro study showed that daidzein at concentrations exceeding 10 micrograms/ml caused inhibition of HL-60 cells; and it induced differentiation of the cells into granulocytic lineage as judged by NBT reduction activity, phagocytic ability and morphological characteristics. Flow cytometry study indicated that daidzein arrested HL-60 cells in the G1 phase. The growth of HL-60 cells in the subrenal capsules of mice and in diffusion chambers implanted into the peritoneal cavities of mice was inhibited by 50 mg/kg daidzein. HL-60 cells treated with daidzein in vivo also exhibited characteristic morphological changes of matured cells. Moreover, the colony forming efficiency of HL-60 cells in diffusion chambers in mice was markedly inhibited by the administration of daidzein. PMID- 8352523 TI - Modulation of c-myc, c-myb, c-fos, c-sis and c-fms proto-oncogene expression and of CSF-1 transcripts and protein by phorbol diester in human malignant histiocytosis DEL cell line with 5q 35 break point. AB - Following exposure to phorbol ester (TPA), DEL cell line, a human malignant histiocytosis (MH) cell line, is able to differentiate along a macrophage phenotype and thus it provides a suitable model for analyzing the sequential and differential gene expression associated with monocyte/macrophage differentiation. C-myc, c-myb, c-fos, c-sis and c-fms expression were determined by Northern analysis at various times following TPA treatment. The results showed that TPA down-modulated the constitutive expression of c-myc, c-myb, and c-fms, mRNA to low but still detectable levels. Conversely, TPA-induced differentiation resulted in transient appearance of c-fos, whereas no change in the level of c-sis and actin transcripts were observed. Thus, the c-fms and c-sis genes appear to be regulated in a specific manner in this malignant histiocytosis derived cell line. Furthermore, these investigations demonstrated a constitutive CSF-1 gene expression which transiently increased at mRNA and also at protein level as evaluated by a murine bone marrow CFU bioassay. Through this drug-induced modulation, the DEL cell line offers an additional model for studying some of the subtle interrelations existing between a growth factor (CSF-1) and its receptor (c-fms) in the monocyte/macrophage system. PMID- 8352525 TI - A protein inhibitor, extracted from Hela cells, which recognises a cell surface protease on preneoplastic cells obtained from cervical smears. AB - Hela cells originate from a clone of cervical carcinoma cells. The cytoplasm of Hela cells contains a protein which recognises and inhibits a proteolytic enzyme (guanidino-benzoatase) on the surface of Hela cells. This same protease is present on the surface of abnormal epithelial cells obtained from cervical smears, enabling a rhodamine labelled inhibitor extracted from Hela cells to locate abnormal cervical cells in monolayer spreads. PMID- 8352526 TI - Association and dissociation of a protease and its inhibitor on the surface of lung squamous cell carcinoma cells. AB - Squamous cell carcinoma cells possess a cell surface protease, referred to as guanidinobenzoatase (GB). GB is a plasminogen-activator-like enzyme which can be located by the fluorescent probe 9-amino acridine in frozen sections. Fluorescence microscopy has been used to study the inhibition of this GB, the displacement of inhibitor from GB, the displacement of GB from the cell surface receptor and the preparation of both active GB and inhibitor, obtained from these frozen sections of tumour tissue. PMID- 8352527 TI - The application of double fluorescence to the rapid selection of atypical cervical epithelial cells spread in monolayers. AB - Monolayer spreads of cervical cells were prepared and reacted in sequence with two fluorescent probes. The nuclei were reacted with 4,6-Diamidino-2-phenylindole (DAPI), resulting in white fluorescence of all cell nuclei. Those cells possessing active guanidinobenzoatase (GB) bound the second probe, rhodamine alpha-N-agmatine (Rh-Agm), resulting in orange cell surface fluorescence. Atypical epithelial cells possessed both active GB and enlarged nuclei; such cells could easily be recognised by their cytological appearance. We illustrate our results in the form of colour prints which are representative of our observations of cells in both normal and abnormal cervical spreads. PMID- 8352528 TI - Regulatory role of mevalonate in the growth of normal and neoplastic human mammary epithelial cells. AB - Treatment with 25-hydroxycholesterol, an inhibitor of HMG CoA reductase activity, efficiently blocked the proliferation of both human normal mammary epithelial cells (HMEC) and breast cancer cells (MDA231). Upon release of the block there was a rapid increase in the HMG CoA reductase activity, which reached a maximum 4 h after removal of the inhibitor, in both cell types. In MDA231 this increase in enzymatic activity was followed by a rapid initiation of DNA synthesis, whereas this process started considerably later in HMEC. Even in HMEC stimulated to DNA synthesis by insulin, there was first an increase in HMG CoA reductase activity with a maximum 4 h after the addition of the mitogen. If 25-hydroxycholesterol was added along with insulin, the subsequent initiation of DNA synthesis was prevented. Following a 25-hydroxycholesterol treatment as short as 4 h, the onset of DNA synthesis was delayed, indicating that a certain level of HMG CoA reductase activity (= mevalonate synthesis) in the early and mid stage of the prereplicative phase is required for the transduction of the signal leading to initiation of DNA synthesis. In concurrence with these data, it was also demonstrated that giving an exogenous supply of mevalonate to the insulin stimulated HMEC results in a faster initiation of DNA synthesis. PMID- 8352529 TI - IL-2 inhibits the induction of systemic antitumour immunity by IL-4 in the peritumoural treatment of experimental melanoma. AB - We have examined the relative abilities of interleukin-4 (IL-4) and interleukin-2 (IL-2) to inhibit the growth of the B.16 melanoma in C57BL/6 mice. Tumours were allowed to become established and then treated peritumourally with either IL-4 or IL-2, or a combination of IL-4 plus IL-2. Treatment was continued for 7 days and then the tumours were removed and weighed. The results showed that IL-4 strongly inhibited tumour growth in 83% of individuals, but complete resolution was observed in only 18%. In the IL-2 treated groups, the percentage of growth inhibited tumours was markedly less (50%), with 14% complete resolutions. In the IL-4+IL-2 treated tumours resolution was again different, such that only 57% of tumours were smaller than those seen in the controls but there was a high number bearing no measurable tumour (25%). In addition, of the three treatments described, only peritumoural administration of IL-4 alone could mediate the induction of systemic protection from tumour growth. These results suggest that IL-4 and IL-2 have different mechanisms of action and that IL-2 may antagonise the effect of IL-4 such that the action of the two materials when combined is highly unpredictable. PMID- 8352530 TI - Differential influence of stromal fibroblasts from different breast tissues on human breast tumour cell growth in nude mice. AB - The influence of human stromal fibroblasts cultured from normal, non-malignant and malignant breast tissues on in vivo growth of human breast tumour cells was studied. Earlier appearance and increased incidence were observed when low cell inocula of breast MDA-MB 231 tumour cells were coinjected with fibroblasts from either normal or non-malignant mammary tissue. However, at higher cell inoculations the appearance of MDA-MB tumours was delayed while the incidence was reduced. Coinjected fibroblasts derived from breast tumours did not modify MDA-MB tumour growth. The tumourigenic MCF-7 and non-tumourigenic NPM14-T4/9 breast cell lines were not affected by the presence of normal breast fibroblasts. These results indicate that fibroblasts can influence the behavior of tumour cells in vivo but the effects depend on the type and the proportions of coinoculated cells. PMID- 8352531 TI - Expression of C-myc p62 oncoprotein in multiple myeloma: an immunohistochemical study of 180 cases. AB - The immunohistochemical expression of C-myc p62 oncoprotein was investigated using the immunoperoxidase method and the monoclonal antibody (Mab) MYC 1-9E10 in bone marrow paraffin sections. 180 cases of multiple myeloma (MM) were studied. C myc expression was found to correlate well with the grade of malignancy, type of myeloma and tumor cell burden (p < 0.001). A relationship was also observed between C-myc p62 and IgA-secreting myelomas. It was found that intermediate grade myelomas are heterogeneous as far as C-myc expression is concerned. Our findings strongly suggest that C-myc might be involved in myelomutagenesis. The evaluation of its expression in MM may be helpful in determining the grade of malignancy and possibly the biological behaviour of this tumor. PMID- 8352532 TI - Analysis of immunohistochemical results of the ras oncogene product p21 in myelodysplastic syndromes. AB - Mutation of the ras oncogenes is the most commonly detected molecular abnormality in acute myelogenous leukemia and myelodysplastic syndromes (MDS). This molecular event may either be acquired by different subclones or by all malignant cells. The availability of the ras p21 monoclonal antibody Y13 259 makes possible the direct study of the distribution of the ras gene product in human malignant cells. The bone marrow smears from 41 patients with MDS were analysed by two independent observers after treatment with MoAb Y13 259, biotinylated goat antirat IgG, streptavidin, peroxidase and staining with diaminobenzidine. A high proportion of strongly positive smears was found among patients with MDS. This positivity was found in 25% of refractory anemia, in 80% of the refractory anemias with excess of blasts, and in 90% of those in transformation, while all 7 cases with chronic myelomonocytic leukemia were found positive. The percentage of positivity may suggest that activation of ras oncogene in associated with disease progression. PMID- 8352533 TI - Exclusion from mammographic screening of women genetically predisposed to breast cancer will probably eliminate mammographically induced breast cancer. AB - In this paper we present our view on the contribution of mammography examinations to breast cancer induction in patients with hereditary breast cancer predisposition. We contradict the usual reasoning that the benefits of early breast cancer detection outweigh the small number of induced breast cancers. Though this tenet is justified in the majority of women, yet in a small, readily identifiable group of hereditary effected women, radiation even in small doses may enhance oncogenesis. If this relatively small group of patients is barred from mammography and regularly screened with other means, mammography may even become a more safe procedure. PMID- 8352534 TI - Oncogenes in cellular immortalisation and differentiation (review). AB - Oncogenes have been shown to be able to overcome the limited proliferative capacity of normal mammalian cells in culture enforcing them to an immortalised phenotype, which in turn may act as a primary step in tumourigenesis. The oncogenes which display such immortalisation activity have the common feature of nuclear localisation, while the oncogenes which are capable of transforming cells are mainly cytoplasmic. Oncogenes from both families have been shown to interfere with the differentiation processes of several cell types. There is evidence that some of these proto-oncogenes may function as regulators of normal cell differentiation, and when immortalisation occurs this is a process of blocking the cell from achieving a differentiated state. This article focuses on the ability of some oncogenes with different functions, such as myc and ras, to override the limited cellular proliferative capacity and their effects on differentiation; finally it examines the recent implications that some onco suppressor genes are actively participating in cellular differentiation processes. PMID- 8352535 TI - Head and neck carcinoma with distant metastases: a retrospective analysis of 44 cases treated with cisplatin-based chemotherapeutic regimens. AB - The rarity of medical reports on the chemotherapeutic management of head and neck cancer metastatic to distant organs prompted us to review the effect of cisplatin based regimens in this clinical setting. Out of 44 eligible patients, 10 patients (23%) achieved a CR, 16 patients (36%) has a PR, 7 (16%) no change, and 11 (25%) progressed. Patients with rhinopharyngeal carcinoma showed a 69% overall response rate, while those with other head and neck carcinomas had a 54% overall response rate. No preferential site of response was detected. The difference in mean survival of responding patients between the rhinopharyngeal group and the non rhinopharyngeal group was statistically significant (P < 0.05). Responding patients survived longer than non responders (P < 0.05 in both groups). Interestingly, 3 patients in the rhinopharyngeal cancer group survived more than 2 years from the start of chemotherapy for metastatic disease. These data strengthen the observation that rhinopharyngeal carcinoma, even with distant metastases, responds to chemotherapy better than other carcinomas arising in the head and neck region. Moreover, although survival is still dismal, cisplatin based systemic chemotherapy seems an effective palliative treatment for metastatic head and neck cancer. PMID- 8352536 TI - Inhibition of antitumor effects of flavone acetic acid by cortisone. AB - The effect of cortisone (2 mg/mouse) on the effect of the antitumour agent flavone acetic acid (NSC 347512) was measured in four different murine tumours, growing subcutaneously. Response was measured by histological assessment of haemorrhagic necrosis after 24 h, and by assessment of tumour growth delay. In C57B1/6 x DBA/2)F1 hosts, cortisone pre-treatment prevented FAA-induced haemorrhagic necrosis in Lewis lung (sub-line LLTC) tumours but did not inhibit necrosis induction in Colon 38 tumours. Similarly in C3H/HeN mice, cortisone pre treatment prevented FAA-induced necrosis of Spon-2 and partially prevented necrosis induction in mammary M-16/C tumours. Since corticosteroids are often administered, or generated internally, in the course of clinical treatment, this result has implications for the clinical use of FAA and other compounds, which act on tumour vasculature as part of their antitumour action. PMID- 8352537 TI - Hepatic vascular lesions associated with malignant lymphomas. AB - Veno-occlusive disease is a serious complication of malignant conditions and often follows irradiation or is drug-induced. We report on the liver histology of a consecutive series of 32 cases of Hodgkin's and non-Hodgkin's lymphomas. Veno occlusive lesions were noted in 27 biopsies prior to treatment. These patients had no apparent malignant infiltrate to the liver. The pathogenesis of these lesions is unclear. PMID- 8352539 TI - Cell cycle related uptake, retention and toxicity of idarubicin, daunorubicin and doxorubicin. AB - Exponentially growing Molt-4 cells were separated by means of counterflow centrifugation into fractions enriched for cells in early G1, late G1, S, or G2+M phase of the cell cycle. Subsequently, cells were exposed for 2 h to Idarubicin (Ida, 0.02-0.15 microgram/ml). Daunorubicin (Dnr, 0.1-0.75 microgram/ml) or Doxorubicin (Dox, 0.1-0.75 microgram/ml). Drug uptake, measured by flow cytometry, increased progressively with cell cycle traverse from early G1-to M phase. The relative fraction of drug lost following an extensive wash procedure was 72% in case of Ida and 23% for Dnr and Dox and was independent of the cell cycle phase. Inhibition of DNA synthesis was determined by qualitative flow cytometric analysis of 5-iodo-2'-deoxyuridine (IdUrd) incorporation into DNA. The three drugs showed a similar gradual increase of inhibition of DNA synthesis from G1 to G2+M phase, demonstrating that cell cycle phase dependency of drug toxicity applies to all three anthracyclines studied. PMID- 8352540 TI - C-myc expression is down-regulated in mafosfamide-treated HL-60 cells undergoing apoptosis. AB - The expression of the proto-oncogene c-myc has been strongly implicated in the regulation of apoptosis. Since we have previously shown apoptosis to occur in HL 60 leukemic cells exposed to the prodrug Mafosfamide (ASTA Z 7557), the present study was undertaken to examine the levels of c-myc mRNA transcripts in such cells. Mafosfamide, which is a cyclophosphamide derivative that rapidly generates 4-Hydroperoxycyclophosphamide after aqueous dissolution, was employed in doses ranging from 0.1 to 20 micrograms/ml. No changes in c-myc mRNA levels were evident after 1 hour of exposure to Mafosfamide. After 6 and 24 hours of Mafosfamide-exposure, however, there was a dose- and time-dependent decrease in c myc transcripts. c-myc mRNA expression was reduced to a greater extent than was either beta-actin of GAPDH expression. Morphological, biochemical and ultrastructural evidence of apoptosis accompanied the Mafosfamide-induced c-myc mRNA down-regulation at 24 hours. We conclude that, in the context of Mafosfamide treated HL-60 cells, upregulation of c-myc mRNA transcription was not fundamental for the activation of the apoptotic cascade. PMID- 8352538 TI - Hypercalcemia of cancer: an update. AB - Hypercalcemia of cancer is due to secretion of substances with parathyroid hormone (PTH)-like activity from tumours of the respiratory, gastrointestinal and urogenital tract as well as hematologic malignancies and breast cancer. PTH related Protein (PTHrP) is secreted mainly from solid tumours and it has been recently recognized as being responsible for hypercalcemia mediated primarily via an increased renal reabsorption of calcium and secondly by an increased bone resorption. PTHrP-mRNA is expressed in a variety of normal tissues and has multiple physiologic and paracrine actions. Bone resorbing factors like the cytokines-lymphokines, interleukins, prostaglandins, TNF-alpha/TNF-beta, GM-CSF/G CSF, TGF-alpha and TGF-beta are produced by certain solid and hematologic cancers and have also been implicated in tumour-induced hypercalcemia. The recently introduced PTHrP antagonists are hopeful therapeutic measures for the future. PMID- 8352541 TI - The difference between benign and malignant tumours explained with the 4-mutation paradigm for carcinogenesis. AB - In recent years a 4-mutation paradigm for carcinogenesis was developed for mutations in tumour suppressor genes. The major tenet of this paradigm is that transformation of a normal cell into a malignant cell is the result of an accumulation of a set of 4 specific cancer mutations. In this paper we show that this paradigm can explain the characteristic differences between benign and malignant tumours. We surmise that benign tumour cells are due to 2 or 3 specific cancer mutations, whereas malignant tumour cells contain 4 specific cancer mutations and 1-3 tumour progression mutations. The following characteristics, essential for differentiating benign and malignant tumours, are explained by our paradigm: (a) differentiation--anaplasia, (b) rate of growth, (c) encapsulation- invasion, (d) metastasis, and (e) the differences in size of benign epithelial and mesenchymal tumours and the relation between tumour size and malignancy. PMID- 8352542 TI - Subcutaneous mastectomy with axillary dissection for early breast cancer. AB - From 1983 to 1990, subcutaneous mastectomy with axillary dissection was carried out for 46 patients with early breast cancer including three bilateral breast cancer patients (four breasts). Cancer cells were recognized histopathologically in the resection margins of small mammary gland resting under the nipple in four cases, and the remaining 42 cases underwent a curative resection. Multicentric lesions were found out histopathologically by continuous sections in five cases (six breasts). There was no difference in the prognosis using the case-control comparison method between 34 patients with ipsilateral invasive carcinoma who underwent a subcutaneous mastectomy in this study group and 34 patients who underwent a radical or modified radical mastectomy in the control group. Cosmetic results of the subcutaneous mastectomy were evaluated in 37 patients, and 9 were excellent, 17 were good, 9 were not so good and 2 were poor. Subcutaneous mastectomy with axillary dissection was an effective operation for early breast cancer including multicentric lesions and some non-invasive ductal carcinomas from the prognostic and cosmetic standpoints. PMID- 8352543 TI - Prospective malignancy grading, flow cytometry DNA-measurements and adjuvant chemotherapy for invasive squamous cell carcinoma of the uterine cervix. AB - In a prospective study comprising 310 consecutive patients with carcinoma of the cervix, FIGO stages I-IV, the prognostic significance of clinical and flow cytometric variable was evaluated in a univariate and multivariate analysis. The parameters studied included stage according to FIGO, age, histopathologic grade according to Ackerman and MGS scores, DNA ploidy, S-phase fraction as well as treatment with radiation only, surgery only or a combination thereof as well as adjuvant chemotherapy. Univariate analysis showed that patients in FIGO stages IA IIA with MGS up to 14 points survived significantly better than other groups. MGS parameter mitosis, vascular invasion and type of invasion predicted survival as did clinical stage. Diploid cases with SPF > 15% survived less than remaining other cases. Multivariate analysis not including treatment indicated that FIGO stage and diploid cases with SPF > 15% predicted survival but not total MGS score and age. When treatment for FIGO stages IA-IIA was included, elderly women had a worse prognosis. Adjuvant chemotherapy, surgical alone or radiation alone did not demonstrate any differences within groups. In Figo stages IIB-IV, cases with radiotherapy only survived significantly better than patients with other treatment schedules. The frequency of low malignancy patients (< MGS 16) in relation to year of initial diagnosis was found to have decreased between years 1967 and 1988, probably as a result of screening activities. PMID- 8352544 TI - Cancer control by family history. AB - Family history can be used to identify persons at high cancer risk and to target appropriate preventive and therapeutic measures. First-degree female relatives of women with breast cancer (n = 600) are at increased risk for breast cancer (RR: 1.7.95% CI: 1.4-1.9). First-degree relatives of colorectal cancer patients (n = 184) are at increased risk for colorectal cancer (RR: 1.8.95% CI: 1.4-2.3). Families with hereditary cancer syndromes are identified. The family history approach can be used in every part of the world, and it should become a part of future cancer control activities. PMID- 8352545 TI - Antitumor activity of homo-aza-steroidal esters of p-N, N-bis(2 chloroethyl)aminophenoxyacetic acid. AB - The homo-aza-steroidal esters of carboxylic derivatives of N, N-bis (2 chloroethyl) aniline are reviewed. In particular, we discuss the antitumor activity of the esters of homo-aza steroids in which the p-N,N-bis(2 chloroethyl)aminophenoxyacetic acid is linked to the C-3 or C-17 position, while the lactam nucleus is linked to the D or A ring of the modified steroid respectively. The current literature indicates clearly that the potential of these esters is due to the synergistic activity of both the lactam and the p-N,N bis(2-chloroethyl)aminophenoxyacetic acid. PMID- 8352546 TI - Growth characteristics of murine B16 melanoma multicellular spheroids: a model for invasion and effects of doxorubicin treatments. AB - Multicellular spheroids, derived from murine B16 melanoma cells, showed unique growth characteristics: when they reached about 500 microns in diameter, their morphology changed rapidly and they became amoeba-like irregular-shaped aggregates. This morphological characteristic closely resembled that of invasive cancer, and may serve as a model for local invasion. To test the possibility that the changes mentioned above can be inhibited by a drug, spheroids were treated with 0.8 microgram/ml of doxorubicin for one hour and their morphology was observed temporally. Although this concentration of the drug decreased the survival of the melanoma cells in monolayer to about 10(-3), the growth was not delayed nor were the "invasion"-like changes inhibited in the spheroids. We believe this system of multicellular spheroids is a useful model to study the mechanisms of tumour invasion, although doxorubicin could not inhibit "invasion" like changes in this system. PMID- 8352547 TI - Different chemo- and endocrino-sensitivity of MCF-7 cells with or without estradiol supplement in vitro. AB - The sensitivity of MCF-7 cells to tamoxifen (TAM) and mitomycin C (MMC) was assessed in rapidly and slowly growing cells with or without estradiol supplementation, respectively. The growth of MCF-7 was inhibited by MMC in a concentration-dependent manner with or without estradiol (E2) supplementation. Preincubation with MMC suppressed subsequent E2 stimulated growth of MCF-7. TAM inhibited the growth of MCF-7 supplemented with E2 and preincubation with TAM prevented subsequent E2 stimulated growth of MCF-7. However, TAM did not inhibit the growth of MCF-7 cells in E2 free medium. These results suggested that MMC may be more effective than TAM on breast cancer cells in the dormant or slow-growth phase. PMID- 8352548 TI - Mechanism for splenocyte-mitogenesis induced in mice by water-extract of coniferous slash pine. AB - A water extract of wood chips of coniferous slash pine induced appreciable splenocyte-mitogenesis in healthy adult, aged, and also tumour-bearing mice. Mitogenesis was induced mainly in B-cell subset of splenocytes. The induction was not mediated by IL-2 or IFN gamma released from the activated helper T-cell. It may be worth noting that this extract could be included in a new type of immunomodulator for promotion of the host defense mechanism. PMID- 8352549 TI - Prognostic factors affecting response to aminoglutethimide in advanced breast cancer. AB - An analysis of 122 patients with advanced breast cancer treated with aminoglutethimide was carried out. Forty-one patients (34%) achieved a complete response or partial response (CR + PR), while 81 patients (66%) remained stable or progressed (S + P). A number of variables were analyzed for their prognostic importance in terms of response to aminoglutethimide. These variables were dominant site of metastases, disease-free survival, estrogen receptor status, age, response to prior tamoxifen, response to chemotherapy administered for metastatic disease, and dose of aminoglutethimide. The most important factors in predicting response were found to be prior response to tamoxifen and a longer disease-free survival after diagnosis. PMID- 8352550 TI - Inhibition of phospholipase D by agents that inhibit cell growth. AB - The phospholipases are an important class of enzymes for growth factor and oncogene intracellular signalling. The anti-tumor drug suramin was found to inhibit phosphatidylcholine hydrolysis and trans-phosphatidylation by solubilized rat brain phospholipase D (PLD) with an IC50 of 15 microM. An azo analogue of suramin, which is a considerably more potent inhibitor of phosphatidylinositol phospholipase C (PIPLC) than suramin, inhibited PLD with and IC50 of 58 microM. D 609, a xanthogenate compound with in vitro antitumor activity, inhibited PLD with an IC50 of 820 microM. The cytotoxic aminosteroid compound U-73, 122 was a weaker inhibitor of PLD with an IC50 of 78 microM. However, U-73, 122 was a more potent inhibitor of PLD in fibroblast membranes with an IC50 of 25 microM, while suramin was less active with an IC50 of 4.2 mM. The antitumor ether lipid drug ET-18-OCH3 did not inhibit solubilized or membrane PLD although it is a potent inhibitor of PIPLC. The results of the study show that the compounds tested have different abilities to inhibit PIPLC and PLD. Access of hydrophilic drugs to membrane PLD may be a limiting factor to their inhibitory activity. PMID- 8352551 TI - Development, characterization and application of an antibody against 5-fluoro 2'deoxyuridine-5'monophosphate, the active metabolite of 5-fluorouracil. AB - 5-Fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) is the active metabolite of the anticancer agent 5-fluorouracil (5FU). Antibodies against a conjugate of thyroglobulin with acetylated FdUMP were raised in 4 rabbits. The maximal titer was reached after 3-5 boosters. Subsequently, the antisera were collected and partially purified. In a competition assay a 100-fold excess of the natural nucleotide dUMP could displace tritiated FdUMP (20 pmol per assay) by about 50% in all antisera. However, tritiated dUMP itself did not bind to the antibody. No cross-reactivity was observed with the FdUMP precursor 5FU and with the natural nucleoside uridine and the nucleotides dTMP, dTTP and UTP. A considerable cross reactivity was observed with the monophosphate of bromodeoxyuridine (Br-dUMP). Radio-immuno assays for FdUMP and dUMP were developed, for which a 100-fold dilution could be used. The FdUMP assay was linear in a range of 0.1 to 5 pmol FdUMP in aqueous solutions. Tumour samples contained a non-identified interfering factor; a similar interference was observed in an enzyme based assay for FdUMP. The dUMP assay was performed by competition of unlabeled dUMP with tritiated FdUMP and was linear from 50 to 2000 pmol dUMP per assay. The antibody recognized FdUMP bound in a ternary complex synthesized in a cell-free system between FdUMP, its target enzyme thymidylate synthase and the folate co-factor. Immunohistochemical staining for demonstration of the ternary complex in 5FU treated cells and tumours from patients and animals was not yet successful, neither with peroxidase nor with immunofluorescence staining. Possibly the amount of bound FdUMP is below the detection limit or FdUMP bound to TS is masked. The antibody may prove to be useful in studies on modulation of FdUMP and dUMP after treatment with thymidylate synthase inhibitors. PMID- 8352552 TI - A preliminary pharmacokinetic evaluation of the antimetastatic immunomodulator swainsonine: clinical and toxic implications. AB - The pharmacokinetics of swainsonine (SW) was investigated in mice after intravenous administration of 3 micrograms/ml. The time course of SW blood levels followed a three-compartment open pharmacokinetic model which consisted of biphasic distribution, and a rapid elimination phase (terminal half-life, 31.6 min). After completion of the distribution, SW was widely distributed to the extravascular space (Vss, 22ml; Vd, 33ml). Free fractions of this substance were indistinguishable from unity, indicating little or no protein binding. The rate limiting step in the elimination of SW from the body appears to be the slow return from the deep compartment into the central one. Accordingly, SW blood levels may be low and yet significant amounts of this agent may be present in different body organs and tissues. A comparison of SW tissue levels indicates that the highest amounts appeared in the bladder, kidney, and thymus, (3.8 0.5, and 2.2 nmoles/g wet wt) with the lowest levels consistently appearing in the brain (< 0.1 nmoles/g wet wt). Hence, this study suggest that: 1) SW has high affinity for the thymus, which is in part consistent with its previously published immunomodulatory action; 2) SW should be infused for at least 2 1/2 hrs for its concentration to approach a plateau (this is based on the short half-life of SW and its time to steady state); and 3) CNS toxicity may be dose-limiting and not be present at SW levels preventing metastasis. PMID- 8352553 TI - Cytogenetic changes in 67 cranial and spinal meningiomas: relation to histopathological and clinical pattern. AB - The cytogenetic analysis of 67 meningiomas (58 intracranial and 9 spinal tumors) identified chromosomal abnormalities in 63% of cases. When chromosomes involved in numerical and structural changes with a frequency of more than one standard deviation above the mean were considered, distinct cytogenetic patterns could be identified according to sex, anatomical location and histology. The chromosomes more frequently affected were 1, 2, 3, 4, 8, 14, 15, 19, 22, Y. No conclusion could be drawn regarding the prognostic significance of these karyotypic alterations. PMID- 8352554 TI - The expression of genes of the steroid-thyroid hormone receptor superfamily in central nervous system tumors. AB - We studied the expression of ten genes (encoding the receptors for glucocorticoid, mineralocorticoid, progesterone, androgen, estrogen, thyroid, retinoid acid, vitamin D) belonging to the steroid-thyroid hormone receptor superfamily (STRS) in 12 neuroepithelial tumors, 12 meningiomas and 2 human glioblastoma cell lines. Our method, based on the polymerase chain reaction, allowed the simultaneous amplification of cDNAs of the STRS genes. On average, 7 STRS genes were simultaneously expressed in each sample. Our study indicates that many STRS gene are commonly co-expressed in human CNS tumors. The importance of our results for the ongoing and proposed hormonal treatment trials is discussed. PMID- 8352555 TI - Pathological features and pyrimidine nucleotide synthesis in human gastric carcinomas. AB - 5-Fluorouracil, a potent anticancer drug, is clinically known to be more effective on a poorly differentiated gastric carcinoma than on a well differentiated type. We investigated activities of thymidylate synthetase (TS) and thymidine kinase (TK) involved in de novo and salvage pathways, respectively, for pyrimidine nucleotide synthesis and histological features in 57 human gastric carcinomas. The average activities of TS in 28 poorly differentiated carcinomas and TK in 29 well-differentiated type were significantly increased to 128 and 166%, respectively, of those in normal gastric mucosa. The TK/TS ratio in the well-differentiated type was 1.7-fold higher than that in the poorly differentiated type. Therefore, the de novo pathway for pyrimidine nucleotide synthesis is so predominant in a poorly differentiated carcinoma, but not in a well-differentiated type, that the potent TS inhibitor 5-FU or its derivatives are suggested to suppress the growth of the poorly-differentiated gastric carcinoma. PMID- 8352556 TI - Potentiating effect of amphotericin B on five platinum anticancer drugs in human cis-diamminedichloroplatinum (II) sensitive and resistant ovarian carcinoma cells. AB - We have determined an effect of amphotericin B (AMB), an antifungal drug, on the cytotoxicity of cis-diamminedichloro-platinum (II) (CDDP) and 4 CDDP analogues in a human ovarian carcinoma cell line (NOS2). Intracellular accumulation of CDDP was elevated significantly by treatment with AMB, and AMB significantly potentiated the cytotoxicity of CDDP by MTT assay. Intracellular accumulation of 4 CDDP analogues was also elevated by the treatment with AMB and the order of increasing accumulation rate of platinum drugs was consistent with that of dose modification factor (DMF). AMB also increased the intracellular CDDP accumulation in CDDP resistant cells (NOS2CR), derived from NOS2. The intracellular accumulations of 4 CDDP analogues were elevated slightly by the treatment with AMB in NOS2CR cells. DMFs of 5 platinum drugs in NOS2CR cells, however, were more than those in NOS2 cells. These results indicate that AMB sensitizes NOS2 and NOS2CR cells to platinum drugs, partially due to the increasing intracellular accumulation of these drugs. In addition, CDDP analogues are more effective in NOS2CR cells than CDDP, but the cytotoxicity of CDDP was most potentiated by AMB among the 5 platinum drugs under study. PMID- 8352557 TI - Complex chromosomal changes in a primary squamous carcinoma of the parotid gland. AB - The chromosomal observations in a cultured primary epidermoid carcinoma of the parotid gland are reported. The tumour had a flat hyper-triploid mode with 7 recurrent wholly or partially identified marker types and 7-13 additional, mostly recurrent, markers, whose origin could not be clarified. There were also many recurring numerical deviations in most tumour cells. The picture was consistent with a neoplasma in an advanced stage of chromosomal progression. So far, 6q markers with varying morphology are the only deviations found in most types of malignant salivary tumours and, in particular, in a high percentage of adenoid cystic carcinomas. One possible explanation for these observations is the occurrence of one or more suppressor genes in 6q which may have relevance for malignant neoplasia in salivary gland tissues. PMID- 8352558 TI - A metastatic orthotopic-transplant nude-mouse model of human patient breast cancer. AB - We report here the development of an orthotopic-transplant model of human patient breast cancer in nude mice. Histologically-intact patient breast tumor tissue was transplanted as intact tissue to the mammary fat pad of nude mice where the tumor tissue grew extensively and metastasized to the lung. This is the first orthotopic-transplant metastatic model of human breast cancer. The potential clinical and basic-science uses of the model are discussed. PMID- 8352559 TI - Evaluation of oral aclarubicin treatment for tumors of the gastrointestinal track. AB - Aclarubicin (ACR), a drug useful for the treatment not only of tumors of the hematopoietic system but also of those of the gastrointestinal tract, has been administered invariably by the intravenous route. We attempted oral administration of ACR to increase its specificity in the treatment of gastrointestinal tumors. Oral administration resulted in a much higher intratumor concentration but lower peripheral blood cell or bone marrow cell concentration of the drug as compared with intravenous administration. The reduced peripheral cell inhibition and bone marrow suppression permits the administration of the drug in higher doses, and the absence of the drug in the plasma suggests a reduced likelihood of myocardial cell injury and hepatocyte impairment. These favorable findings are considered to warrant early clinical trial of the treatment. PMID- 8352560 TI - Induction of NK-like activity in T cells by IL-2/anti-CD3 is linked to expression of a new antitumour receptor with specificity for acetylated mannose. AB - The generation of MHC-unrestricted cytotoxicity of highly enriched human CD3+ T cells (95-99%) by treatment with IL-2 and/or anti-CD3 antibodies was studied. T cells obtained by positive immunomagnetic sorting (anti-CD3) developed comparable specific cytotoxicities against K562 and Daudi cells when cultured with IL-2 and anti-CD3 for 96 h (80% of donors; n = 25). This increase of MHC-unrestricted cytotoxicity correlated fairly well with an increased formation of T cell/tumour cell conjugates. Moreover, simultaneous expression of a rhamnogalacturonan binding receptor on activated T cells could be demonstrated. Rhamnogalacturonan was reported to enhance cytotoxicity of CD56+ NK cells by effector cell/target cell bridging. Untreated CD3+ cells hardly reacted with rhamnogalacturonan and IL 2-activated T cells showed only a moderate enhancement of cytotoxicity in the presence of rhamnogalacturonan. However, when CD3+ T cells had interacted with anti-CD3 antibodies during cell-sorting or during subsequent culturing with IL-2, enhancement in cytotoxicity and increased formation of lytic effector cell/tumour cell conjugates in the presence of rhamnogalacturonan could be readily demonstrated, indicating a bridging effect analogous to CD56+ NK cells. The conjugate formation of activated T cells with tumour cells as well as the additional rhamnogalacturonan-mediated bridging must be based on the expression of receptors with acetyl mannose specificity, since enhancements of MHC unrestricted T cell cytotoxicity and conjugate formation were inhibited in a dose dependent manner when acetylated mannose was present in the assays. PMID- 8352561 TI - Effect of promegestone, tamoxifen, 4-hydroxytamoxifen and ICI 164,384 on the oestrone sulphatase activity of human breast cancer cells. AB - In the present study, we explored the effects on sulphatase activity by Promegestone (R-5020), Tamoxifen (TAM), 4-hydroxytamoxifen (4-OH-TAM) and ICI 164,384 in the T-47D hormone-dependent and MDA-MB-231 hormone-independent mammary cancer cell lines. Using homogenates of these cells it was observed that Promegestone has a significant effect on the inhibition of oestrone (E1) sulphatase activity. As this effect is competitive, it is suggested that there is a direct action of this compound on the enzyme. Tamoxifen has very little or no effect, 4-hydroxytamoxifen has an intermediate effect and ICI 164,384 is active in the enzyme inhibition, particularly with MDA-MB-231 cells. The present data could open new possibilities for human breast cancer treatment, as sulphatase is very active in the first step of the conversion of oestrone sulphate (E1S) to oestradiol (E2), and oestradiol is one of the principal carcinogenic factors in human hormone-dependent breast cancer. PMID- 8352562 TI - Mode of action of estra-1,3,5(10)-triene-3, 17 beta-diol, 3-benzoate, 17[4-[4 [bis(2-chloroethyl)amino]phenyl]-1-oxobutoxy] acetate] (KM2210) on MCF-7 human breast tumours transplanted into nude mice. AB - KM2210 is a benzoate of an estradiol-chlorambucil conjugate with three active metabolites, KM2202, estradiol (E2) and chlorambucil (CBL). The mode of action of this compound was assessed using MCF-7 human breast tumours transplanted into nude mice. The growth of MCF-7 in nude mice was inhibited by KM2210 and enhanced by E2, although the serum levels of E2 in nude mice treated with KM2210 and E2 were similar. The antitumour activity of CBL was completely blocked by extrinsic E2, while KM2210 suppressed the growth of MCF-7 in spite of the presence of E2 in the serum of tumour-bearing nude mice. KM2210 and KM2202 suppressed the expression of cytosol estrogen receptor (ER) of MCF-7 cells detected by the dextran-coated charcoal and fluorescent E2 staining method, although CBL did not affect the ER expression of MCF-7 cells. This inhibitory effect of KM2210 on ER was also corroborated by the fact that the pretreatment with KM2210 prevented the E2-stimulated growth of MCF-7 in nude mice. These results indicated that one of the effects induced by KM2210 is the blockage of ER expression in combination with the alkylating antitumour activity of CBL. KM2210 is thought to be a promising agent with unique modes of action for ER-positive breast carcinomas. PMID- 8352563 TI - Lack of influence of c-Ha-ras expression on the drug sensitivity of human bladder cancer histocultured in three-dimensions. AB - The mechanism of drug resistance in human cancers is complex. In addition to overexpression of a series of multiple-drug-resistance genes, there has been the suggestion that the Ha-ras gene may participate in conferring resistance. In this study, a series of three human-bladder carcinoma cell lines were studied, one parental type, one transfected by wild-type Ha-ras and another transfected by mutant Ha-ras. The ras gene was overexpressed in the latter two cell lines which also were more invasive than the parental when injected as individual cells in the nude-mouse bladder. The results described here have indicated that the ras gene expression level or mutational status did not affect drug resistance when the tumor lines were histocultured as three-dimensional tissue on collagen-sponge gels. The drug-response spectrum of the histocultured lines qualitatively reflected a clinical experience although all lines were relatively drug resistant, possibly reflecting their three-dimensional configuration in culture. PMID- 8352565 TI - Metabolism of new anticancer oxysterol derivatives in rats. AB - New water soluble derivatives of oxysterols--the phosphodiesters of oxysterols and of nucleosides--have been synthesized. In vitro, these compounds share the biological properties of their parent oxysterols. Furthermore, they display anticancer activity when injected i.p. in mice bearing experimental tumors. The pharmacokinetic study described here proved that the water-soluble derivatives of oxysterols act as prodrugs releasing free oxysterol in the blood, the liver and the kidney after i.p. or i.v. injection in rats. The hydro-solubility of such compounds as well as their slow metabolism into the active principle could account for their biological activity and make them suitable as new therapeutic agents. PMID- 8352564 TI - Inhibition of DNA repair in cells treated with a combination of alkylating agents. AB - Aphidicolin (AP) or hydroxyurea (HU) inhibited DNA repair and enhanced cytotoxicity in human ovarian carcinoma cells A2780 treated with L-phenylalanine mustard (L-PAM) combined with cisplatin or thioTEPA, and in the cells treated with cisplatin combined with thioTEPA. In cultures treated with L-PAM or cisplatin alone post-treatment with AP or HU had no effect on DNA repair and produced only additive cytotoxicity. Post-treatment with AP + HU inhibited DNA repair and enhanced cell killing in cultures treated with L-PAM alone. The inhibitor of protein synthesis cycloheximide protected cells from the cytotoxicity of AP + HU but had no effect on synergistic cell killing produced by DNA repair inhibition. In cisplatin-resistant cells A2780/CP post-treatment with AP + HU enhanced the cytotoxicity of L-PAM, but not of cisplatin. However, in resistant cells treated with cisplatin combined with L-PAM or thioTEPA DNA repair inhibitors decreased IC90 of cisplatin. Treatment of cells with two alkylating agents enhanced the sensitivity to DNA repair inhibitors and eliminated low sensitivity to inhibitors of repair associated with drug resistance. PMID- 8352566 TI - The reversal of multidrug resistance in cancer (review). AB - A brief review of the "state of the art" (1992) knowledge concerning various strategies and tactics to overcome multidrug resistance is presented. Multidrug resistance remains the main obstacle to long-term successful cancer chemotherapy; its prevention or elimination is probably one of the most promising avenues in cancer research. PMID- 8352567 TI - Effects of serine protease inhibitor FOY-305 and heparin on the growth of squamous cell carcinoma. AB - Effects of serine proteinase inhibitor FOY-305 and heparin on autochthonous skin carcinoma were examined using ddY female mice with single tumor induced by methylcholanthrene. FOY-305 given intraperitoneally for 9 consecutive weeks inhibited the growth of the pre-existing dermal tumors. Heparin alone was equally therapeutically effective. However, heparin induced severe mucocutaneous bleeding of the gastrointestinal mucosa. In contrast, the combined administration of FOY 305 and heparin suppressed tumor growth without any visible side effects. There was a significant increase in well differentiated cancer cells in mice treated with FOY-305 and heparin in combination, suggesting that co-administration of FOY 305 and heparin may be useful for the treatment of squamous cell carcinoma. PMID- 8352568 TI - Difluoromethylornithine and ethylglyoxal bis(guanylhydrazone) as inhibitors of human renal carcinoma cell proliferation and polyamine metabolism. AB - The significance of the polyamines putrescine, spermidine and spermine for the neoplastic proliferation of the human renal carcinoma cell line ACHN was investigated. For this purpose cells were cultured in vitro for 4 days with or without the addition of pathway inhibitors of polyamine biosynthetic enzymes. It was found that treatment of ACHN cells with the specific ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO) resulted in profound decreases of ODC activity, polyamine content and cell proliferation rates along with a compensatory increase in S-adenosylmethionine decarboxylase (SAMDC) activity. Ethylglyoxal bis(guanylhydrazone) (EGBG), a SAMDC inhibitor, evoked a similar reduction of cell proliferation and contents of spermidine and spermine. EGBG also seemed to stabilize SAMDC, as evidenced by a highly enhanced SAMDC activity during enzyme assays in the absence of the inhibitor. Furthermore, EGBG treatment caused on activation of ODC and a subsequent build-up of putrescine. The impact on polyamine contents and proliferation rates were synergistic when the inhibitors were used in combination. None of the inhibitors alone exerted a cytocidal activity. It is concluded that polyamines may be implicated in the regulation of the neoplastic proliferation of cultured human renal carcinoma cells and that polyamine synthesis inhibitors may prove valuable in clinical treatment of this disease. PMID- 8352569 TI - Effect of duration of exposure to S9788, cyclosporin A or verapamil on sensitivity of multidrug resistant cells to vincristine or doxorubicin. AB - In order to explain the high potency of S9788, a new multidrug resistance modifier currently in clinical development, we investigated its accumulation and retention in sensitive and resistant cells. Our results show that S9788 is 13 fold more accumulated and 23-fold more retained than VRP in the resistant S1/tMDR cell line. We also studied the effect of duration of incubation on the ability of S9788, verapamil and cyclosporin A to overcome the resistance of S1/tMDR and KB A1 cells to a short exposure of doxorubicin or vincristine. Compared to a single co-incubation of 4 h, a 24 h post-incubation with 5 microM S9788 markedly increased the reversal of S1/tMDR resistance to VCR (fold reversal 4 h = 123; fold reversal 24 h = 4739), while it moderately increased S1/tMDR sensitivity to DOX (fold reversal 4 h = 1.9; fold reversal 24 h = 2.9). Similar results were obtained on KB-A1 resistance to VCR (fold reversal 4 h = 41, fold reversal 24 h = 21819) and KB-A1 resistance to DOX (fold reversal 4 h = 89; fold reversal 24 h = 160). This phenomenon also occurred with verapamil and cyclosporin A. These results clearly show that the effect of duration of exposure on the modulating activity of S9788 and of the 2 other modulators depends on the cytotoxic drug. Although the direct transposition of these results to a clinical situation is difficult, they suggest that a continuous infusion of S9788, starting simultaneously with the administration of the cytotoxic drug and ending 24 h later, might be a more effective schedule for clinical administration than a bolus administration. PMID- 8352570 TI - [Male impotence. An introduction]. PMID- 8352571 TI - [Flaccidity and erection of the human penis: morphological data]. AB - Erection of the human penis, a simple and at the same time complex phenomenon, requires the involvement of numerous sustaining mechanisms. This paper presents a summary of the morphological research work done by the author, mainly concerning the mechanisms regulating the blood flow distribution in the arteries and veins, the arteriovenous anastomoses, the two corpora cavernosa of the penis with their tunica albuginea, the urethral corpus spongiosum, the capsular membrane which envelopes the latter, and finally the paraurethral glands. Although it is true that the primary mechanism of penile erection is represented by the central and peripheral nervous system, it must not be forgotten that the basis for this phenomenon consists of the structures of the corpora cavernosa of the penis as well as all of the other penile morphological structures. PMID- 8352572 TI - [Erection disorders: the value, significance and limits of various examinations]. AB - Erection, a complex physiological phenomenon, is the result of numerous simultaneously interacting mechanisms. A defect of one of these mechanisms can induce erectile dysfunction. In this paper, the authors define the various tests used to investigate the principal pathways governing erection, taking into account their respective value in view of the increasing pressure of budget restrictions on health systems. PMID- 8352573 TI - [Neurologic and neurophysiologic studies of impotent patients]. AB - A multispeciality approach of impotent patients are necessary to establish the cause of impotence. Neurological history and examination are very important and must be completed by neurophysiological investigations. Bulbo-cavernosus reflex, conduction velocity of the dorsal nerve of penis and pudendal evoked potentials seems the most interesting tests. Urodynamics, perineal EMG, penile vibratory sensibility test can help determination of some peripheral neuropathies. Single potential analysis of cavernous electric activity may be useful in diagnosis of pudendal autonomic dysfunction. PMID- 8352574 TI - Single potential analysis of cavernous electrical activity (SPACE). Experiences, limitations and perspectives. AB - Cavernous electromyography was first introduced by Wagner and Gerstenberg in 1989. The authors developed a refined method of cavernous electromyography by means of single potential analysis in introduced this method into clinical Urology as a diagnostic procedure for the evaluation of patients presenting with erectile dysfunction. To date, our experience with single potential analysis of cavernous electrical activity (SPACE) includes more than 500 patients with erectile dysfunction of various etiologies and 92 normal control subjects. Several technical modifications and refinements have been adopted during the last 4 years. In normal control subjects, SPACE shows a regular pattern of activity with long phases of electrical silence at the usual amplification interrupted by synchronous low frequency, high amplitude potentials. In patients with disruption of the peripheral autonomic supply, typical asynchronous potentials with higher frequencies and irregular shape are observed. In complete spinal cord lesions, abnormal as well as normal electrical activity is found. In patients with a long history of insulin-dependent diabetes and presumably cavernous smooth muscle degeneration, SPACE recordings show irregular potentials with low amplitudes and slow depolarization speed. Synchronization of electrical activity is usually absent. Recent studies on patients with venous leakage show that SPACE provides independent clinical information about the cavernous smooth musculature. The recording of cavernous electrical activity is possible and reproductible. In the future, a new software for one-line date processing, storage and interpretation of SPACE signals will be available. PMID- 8352575 TI - [Revascularization of the penis in cases of male impotence of vascular origin]. AB - In arteriogenic erectile dysfunction, representing about 80 percent of all organic forms of impotence, a purely arteriogenic impotence is distinguished from a venous leakage. The former can be treated with promising results by means of arterial revascularization. In this respect it is worth mentioning that this form of impotence may also occur following pelvic surgery. Furthermore, diabetes mellitus at an early stage may be responsible for erectile dysfunction. A venous leakage, however, is not a disease of the veins but of the cavernous tissue. In most cases ischemic diseases are due to arterial lesions. In our experience have found that this disease can be treated with the chance of good results by means of our technique of arterial revascularization combined with penile banding. PMID- 8352576 TI - [Prostaglandin E1--the pharmacologic prosthesis]. AB - The treatment of erectile failure has developed rapidly over the last decade with the introduction of intracavernosal self injection therapy, first with phenoxybenzamine, then with papaverine and paraverine-phentolamine. These drugs are now progressively replaced by prostaglandin E1 mainly because of its efficacy and fewer side effects. Prostaglandin E1 can induce a rigid erection even in case of severe arteriopathy and offers an excellent alternative to a prosthetic implant. PMID- 8352577 TI - [The value and limits of the use of mechanical erection aids in the treatment of erection disorders]. AB - Mechanical devices for assisting erection are gaining a wider interest and are of significant importance in the treatment of erectile dysfunction. The authors have assessed their contribution to the treatment of impotence in 36 patients at our outpatient Andrology clinic/CHUV. (31 patients with organic impotence, the remaining five being of psychogenic origin). PMID- 8352578 TI - [The preservation of penile erection during complete prostato-vesiculectomy for carcinoma of the prostate]. AB - At present radical prostatovesiculectomy is the most reliable procedure for curing a locally confined prostatic carcinoma with no evidence of metastases. The prostatic apex represents the most critical aspect in this operation. A part of the symphysis is resected to obtain a better view of the apex. The technique of sparing the nerves and arteries which are necessary for erection is described. However, nerve sparing radical prostatectomy should only be considered up to a clearly confirmed stage T2. PMID- 8352579 TI - [Supra-systolic elevation of the intra-cavernous pressure secondary to stimulation of the glans penis]. AB - The role of the perineal muscles in human penile erections is still controversial. The authors investigated surface electromyographic activity of the ischiocavernous muscles together with intracavernous pressure recordings during pressure stimulations of the glans penis. Successive glans stimulations were associated with ischiocavernous muscle contractions and increases in intracavernous pressure reaching two- to fourfold the systolic blood pressure. High correlation coefficients were found between electromyographic and intracavernous pressure amplitudes. Voluntary contractions were accompanied by intracavernous pressure peaks of similar durations, and areas delineated by integrated electromyographic and intracavernous pressure curves showed very high correlation coefficients. Anaesthesia of the dorsal nerve resulted in dramatic reductions of muscle activity and intracavernous pressures in response to glans stimulation. These results suggest that the activity of the muscles in response to pressure stimulation of the glans penis is important to augment rigidity during vaginal penetration and intercourse due to their ability to increase intracavernous pressures. PMID- 8352580 TI - [Considerable increase in the perineal arterial flow secondary to stimulation of the glans penis]. AB - The authors investigated the changes in human perineal blood flow by Doppler ultrasonography before, during, and after pressure stimulations (30,150 mm Hg) applied to the glans penis. We found a local increased blood flow response in 72% of 50 patients who consulted our center for erectile dysfunctions. Precise measurement analyses of 10 of these subjects allowed us to further characterize this response. Its latency ranged from 0.1 to 0.8 sec. and its duration from 4 to 13 sec. The blood flow increased up to 8 times the prestimulation level. This consistent increase in perineal blood flow showed much less variability than either the latency or duration of the response. The results of this study suggest that intravaginal pressures exerted on the glans penis during vaginal penetration and intercourse trigger an augmentation of blood flow into the corpora cavernosa. The reflex nature of this response is currently under investigation. PMID- 8352581 TI - Intracavernous application of SIN-I in rabbit and man: functional and toxicological results. AB - The mode of action of the active metabolite SIN-I of the vasodilator prodrug molsidomine was studied in vitro and in vivo in corpus cavernosum of rabbit and man. SIN-I produces a dose-dependent relaxation of isolated human cavernous smooth muscle strips. In the rabbit, the intracavernous application of SIN-I increased the intracavernous pressure to a full erection (approximately 100 cm H2O). This response was highly reproductible. SIN-I was also injected intracavernously 6 times in five rabbits over 2 weeks; no inflammatory or fibrotic reactions were found on histology. SIN-I may be a reliable drug for the treatment of impotence without side-effects. PMID- 8352582 TI - [Flexible penile implants in the restoration of erectile function]. AB - Flexible penile implants not only allow sexual penetration due to their physical properties, but also frequently induce restoration of real erection due to the reduction of the venous bed with preservation of the cavernous arteries. The author reports a series of 53 penile implant insertions. Restoration of erection above the horizontal was observed in 60% of cases with good tumescence of the glans. PMID- 8352583 TI - [A biomechanical study of flexible penile implants]. AB - The prostheses used are silicone elastomer flexible penile implants. They are not hard, but flexible and capable of being elongated without traction. These implants have the advantage of resisting axial pressure which facilitates intromission, even in the absence of erection. Their flexibility also allows the penis to hang when the patient is standing. For the penis to hang normally, it must be sufficiently long (hence the value of cavernopubic release) and the intracavernous cavity must be longer than the prosthesis. The prosthesis does not alter the cavernous artery, but markedly flattens the venous plexus (lakes and efferent veins). PMID- 8352584 TI - From bacterial nutrition to enzyme structure: a personal odyssey. PMID- 8352585 TI - Protein tyrosine phosphatases. PMID- 8352586 TI - The structure and biosynthesis of glycosyl phosphatidylinositol protein anchors. PMID- 8352587 TI - Structural and genetic analysis of protein stability. AB - One very encouraging development has been the freedom with which amino acid replacements can be introduced in a protein of interest. This has made it possible to obtain detailed structural and thermodynamic data on a wide variety of mutants that modify protein stability. Substitutions of solvent-exposed amino acids on the surfaces of proteins are seen to have little if any effect on protein stability or structure, leading to the view that it is the rigid parts of proteins that are critical for folding and stability. There is every reason to expect that it will be possible to rationalize the stabilities of mutant proteins from accurate knowledge of their structures. Substantial progress is being made in quantitating the interactions that determine and stabilize protein structures. Although not specifically the subject of this review, substantial progress is also being made in developing methods to engineer proteins of enhanced stability. PMID- 8352588 TI - General initiation factors for RNA polymerase II. PMID- 8352589 TI - Human gene therapy. PMID- 8352590 TI - Nucleocytoplasmic transport in the yeast Saccharomyces cerevisiae. PMID- 8352591 TI - hnRNP proteins and the biogenesis of mRNA. PMID- 8352592 TI - Eukaryotic DNA replication: anatomy of an origin. PMID- 8352593 TI - Membrane partitioning during cell division. PMID- 8352594 TI - Cytoplasmic microtubule-associated motors. PMID- 8352595 TI - New photolabeling and crosslinking methods. PMID- 8352596 TI - Structure-based inhibitors of HIV-1 protease. PMID- 8352597 TI - Introns as mobile genetic elements. PMID- 8352598 TI - Analysis of glycoprotein-associated oligosaccharides. PMID- 8352599 TI - Pathways of protein folding. AB - Advances in spectroscopy, protein engineering, and peptide synthesis have had a dramatic impact on the understanding of the structures and stabilities of transient folding intermediates. The data available from a variety of proteins point to the existence of three common stages of folding. 1. Initially, the unfolded protein collapses to a presumably more compact form containing substantial nonpolar surfaces and secondary structure. This species has little thermodynamic stability and encompasses an ensemble of conformations that are in dynamic equilibrium and may contain non-native elements of structure. This reaction occurs in less than 5 ms and, from a thermodynamic perspective, may be a noncooperative transition. The relatively high content of secondary structure implies that this manifold of states must be far smaller than the manifold for the unfolded protein. 2. The next phase involves the further development of secondary and the beginnings of specific tertiary structure throughout the protein as well as of measurable stability. Nativelike elements of structure appear, possibly in the form of subdomains that are yet to be properly docked. In many instances, the packing is not as tight as is ultimately found in the native conformation, suggesting that the side chains are in general more mobile. Some elements of surface structure, such as loops and the peripheries of sheets and helices, are not yet well defined. This stage, which may consist of more than a single kinetic step, occurs in the 5-1000 ms time range. The ensemble of conformations is much reduced from the first stage; however, it is far from a single, highly populated form. 3. The final stage in folding corresponds to the concerted formation of many noncovalent interactions throughout the protein. The solidlike interior packing is achieved; the final secondary structure forms and the surface structures settle into place. The breadth of these conformational changes reflects the global cooperativity characteristic of protein folding reactions. A pictorial representation of the kinetic and thermodynamic aspects of this process is shown in Figure 1. This folding scheme emphasizes the progressive development of structure and stability through an ever-slowing set of reactions. Because the product of each stage of folding, with the exception of the final step, is an ensemble of related but not identical species, it is an oversimplification to describe the process as a pathway. Perhaps it is better described as a series of transitions between manifolds of structures that are in dynamic equilibrium within any given set.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8352600 TI - Cognition, mechanism, and evolutionary relationships in aminoacyl-tRNA synthetases. PMID- 8352601 TI - Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions. AB - Basic mechanisms that underlie the oxygen free radical-promoted oxidation of free amino acids and amino acid residues of proteins are derived from radiolysis studies. Results of these studies indicate that the most common pathway for the oxidation of simple aliphatic amino acids involves the hydroxyl radical-mediated abstraction of a hydrogen atom to form a carbon-centered radical at the alpha position of the amino acid or amino acid residue in the polypeptide chain. Addition of O2 to the carbon-centered radicals leads to formation of peroxy radical derivatives, which upon decomposition lead to production of NH3 and alpha ketoacids, or to production of NH3, CO2, and aldehydes or carboxylic acids containing one less carbon atom. As the number of carbon atoms in the amino acid is increased, hydrogen abstraction at other positions in the carbon chain becomes more important and leads either to the formation of hydroxy derivatives, or to amino acid cross-linked products as a consequence of carbon-centered radical recombination processes. alpha-Hydrogen abstraction plays a minor role in the oxidation of aromatic amino acids by radiolysis. Instead, the aromatic ring is the primary site of attack leading to hydroxy derivatives, to ring scission, and in the case of tyrosine to the formation of Tyr-Tyr cross-linked dimers. The basic pattern for the oxidation of amino acids by metal ion-catalyzed reactions (Fenton chemistry) is similar to the alpha-hydrogen abstraction pathway. But unlike the case of oxidation by radiolysis, this Fenton pathway is the major mechanism for the oxidation of all aliphatic amino acids, regardless of chain length, as well as for the oxidation of aromatic amino acids. Curiously, the Fe(III)-catalyzed oxidation of free amino acids is almost completely dependent upon the presence of bicarbonate ion, and is greatly stimulated by iron chelators at chelator/Fe(III) ratios less than 1.0, and is inhibited at chelator/Fe(III) ratios greater than 1.0. It is deduced that the most active catalytic complex is composed of two equivalents of HCO3-, an amino acid, and at least one equivalent of iron; however, two forms of iron, an iron-chelate and another form, must somehow be involved. In contrast to the situation with radiolysis, the aromatic rings of aromatic amino acids are only minor targets for metal-catalyzed reactions. All amino acid residues in proteins are subject to attack by hydroxyl radicals generated by ionizing radiation; however, the aromatic amino acids and sulfur-containing amino acids are most sensitive to oxidation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8352602 TI - The receptors for nerve growth factor and other neurotrophins. PMID- 8352603 TI - Function and regulation of ras. PMID- 8352604 TI - Control of transcription termination by RNA-binding proteins. PMID- 8352605 TI - Cosmetic tattoo ink darkening. A complication of Q-switched and pulsed-laser treatment. AB - BACKGROUND: High-energy, short-pulse lasers, eg, Q-switched lasers, emitting visible and near-infrared light have recently been developed for removing tattoos, with little risk of scarring. The mechanisms of action, and possible adverse effects other than scarring and hypopigmentation, are not fully understood. OBSERVATIONS: We describe five cases of pulsed-laser-induced, immediate, irreversible darkening of cosmetic, white, flesh (skin-color), and pink-red colored tattoos. Irreversible ink darkening can be an insidious complication, because immediate whitening of the skin temporarily obscures the subsequently impressive color change. Among these cases, irreversible ink darkening occurred with Q-switched ruby (694 nm), Q-switched neodymium (Nd):YAG (1064 nm/532 nm), and pulsed green dye (510 nm) lasers. Attempts to remove the darkened ink with further laser treatment failed in two cases, and surgical excision was necessary. In the other three cases, subsequent laser treatments successfully removed the darkened ink. The red cosmetic tattoo ink used in one of the cases was placed in agar in vitro and was converted to a black compound immediately on Q-switched ruby laser exposure. Ferric oxide, a brown-red ingredient commonly used in cosmetic tattoos, was similarly tested and blackened in vitro by Q-switched ruby laser exposures. CONCLUSIONS: Although most tattoos are not darkened by laser treatment, short-pulsed lasers over a wide spectrum can cause immediate darkening of some tattoo inks. Patients should be warned of the potential for irreversible cosmetic tattoo darkening, and test-site exposures should be performed prior to treatment. In some cases, subsequent laser treatments may remove the blackened ink. The mechanism probably involves, at least for some tattoos, reduction of ferric oxide (Fe2O3, "rust") to ferrous oxide (FeO, jet black), but the chemical reaction that is involved remains unknown. PMID- 8352606 TI - Disseminated infection with Trichosporon beigelii. Report of a case and review of the cutaneous and histologic manifestations. AB - BACKGROUND: Trichosporonosis is a potentially life-threatening disseminated infection with Trichosporon beigelii, the causative agent of the white piedra. Systemic infection by this fungus has been most frequently described in immunocompromised hosts with neutropenia, but one case has been reported in the acquired immunodeficiency syndrome setting. We report a second case of trichosporonosis in a patient with acquired immunodeficiency syndrome and review the clinical and histologic characteristics of cutaneous involvement with this opportunistic fungal pathogen. OBSERVATIONS: Trichosporonosis occurs most commonly in neutropenic patients receiving chemotherapy. We describe the second case developing in the acquired immunodeficiency syndrome setting. Cutaneous involvement occurred in approximately 30% of patients and most frequently presented as purpuric papules and nodules with central necrosis or ulceration. Biopsy specimens of these lesions revealed dermal invasion by fungal elements, and culture was positive in greater than 90% of the cases. CONCLUSIONS: Disseminated infection with T beigelii can occur in immunosuppressed patients, including those with acquired immunodeficiency syndrome particularly if associated with neutropenia. Cutaneous involvement is common, presenting as purpuric papules and nodules. Biopsy and culture of cutaneous findings can help establish an accurate diagnosis resulting in rapid and appropriate treatment. PMID- 8352607 TI - Lasers in dermatology--1993. PMID- 8352608 TI - Ulcerated nodules on the elbows, fingers, and knees. Erythema elevatum diutinum (EED). PMID- 8352610 TI - Papules and plaques over the joint spaces. Knuckle pads (heloderma). PMID- 8352609 TI - Tense bullous lesions on fingers. Orf. PMID- 8352612 TI - Dermatology's resident match: it's time for change. PMID- 8352611 TI - Irregularly pigmented hyperkeratotic plaque on the thumb. Bowen's disease. PMID- 8352613 TI - Expression of toxic epidermal necrolysis in grafted skin is donor-site dominant. PMID- 8352614 TI - Incidence of Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with the acquired immunodeficiency syndrome in Germany. PMID- 8352615 TI - Heterogeneity of polymorphous light eruption: a study of 105 patients. PMID- 8352616 TI - Acquired uncombable hair. PMID- 8352618 TI - Plantar erythema nodosum: cases in two children. PMID- 8352617 TI - Sweet's syndrome and mediastinal lymphadenopathy due to sarcoidosis: three cases of a new association. PMID- 8352619 TI - Confluent and reticulated papillomatosis. Treatment with etretinate. PMID- 8352620 TI - Ominous Tzanck smears in primary herpes simplex virus infection. PMID- 8352621 TI - The Q-switched Nd:YAG laser effectively treats tattoos. A controlled, dose response study. AB - BACKGROUND AND DESIGN: The Q-switched ruby laser was recently shown to remove tattoos without scarring. The Q-switched neodymium: yttrium aluminum garnet (Nd:YAG) laser, which targets black ink with a longer wavelength that has less absorption by melanin, should effectively treat tattoos with fewer pigmentary alterations. A prospective, blinded, controlled study was conducted to assess the ability of the Q-switched Nd:YAG laser (1064 nm, 10 ns, 5 Hz) to remove tattoos. Twenty-five patients with 39 blue-black or multicolored tattoos (14 previously untreated, 25 Q-switched ruby laser-resistant) were exposed in randomly derived quadrants with 6, 8, 10, or 12 J/cm2 at 3 to 4 week intervals for a total of four treatment sessions. RESULTS: An excellent response (> 75% ink removal) was seen in 77% of the black tattoos and more than 95% of the black ink cleared in 11 (28%) of 39 tattoos at 10 to 12 J/cm2 after four treatment sessions. Colored inks were not as effectively removed. Response was related to fluence with greatest improvement noted in the quadrants treated with 10 and 12 J/cm2. No significant side effects, including pigmentary changes or scarring, were noted. Histopathologic examination demonstrated persistence of tattoo ink in clinically clear areas and confirmed the absence of fibrosis and granulomatous changes. CONCLUSION: The Q-switched Nd:YAG laser (1064 nm) effectively treats black tattoos with an excellent cosmetic outcome. Bright colors were minimally responsive to treatment. Higher doses were more effective and equally well tolerated. PMID- 8352622 TI - Skin graft take and healing following 193-nm excimer, continuous-wave carbon dioxide (CO2), pulsed CO2, or pulsed holmium: YAG laser ablation of the graft bed. AB - BACKGROUND: Ablative lasers have been used for cutaneous surgery for greater than two decades since they can remove skin and skin lesions bloodlessly and efficiently. Because full-thickness skin wounds created after thermal laser ablation may require skin grafting in order to heal, we have examined the effect of the residual laser-induced thermal damage in the wound bed on subsequent skin graft take and healing. In a pig model, four different pulsed and continuous-wave lasers with varying wavelengths and radiant energy exposures were used to create uniform fascial graft bed thermal damage of approximately 25, 160, 470, and 1100 microns. Meshed split-thickness skin graft take and healing on the thermally damaged fascial graft beds were examined on a gross and microscopic level on days 3 and 7, and then weekly up to 42 days. RESULTS: Laser-induced thermal damage on the graft bed measuring greater than 160 +/- 60 microns in depth significantly decreased skin graft take. Other deleterious effects included delayed graft revascularization, increased inflammatory cell infiltrate at the graft-wound bed interface, and accelerated formation of hypertrophied fibrous tissue within the graft bed and underlying muscle. CONCLUSIONS: Ablative lasers developed for cutaneous surgery should create less than 160 +/- 60 microns of residual thermal damage to permit optimal skin graft take and healing. Pulsed carbon dioxide and 193-nm excimer lasers may be valuable instruments for the removal of full thickness skin, skin lesions, and necrotic tissue, since they create wound beds with minimal thermal damage permitting graft take comparable to that achieved with standard surgical techniques. PMID- 8352623 TI - Precise ablation of skin with reduced collateral damage using the femtosecond pulsed, terawatt titanium-sapphire laser. AB - BACKGROUND AND DESIGN: The precise ablation of skin was studied using an ultrashort-pulsed, high-intensity titanium-sapphire (Ti:Al2O3) laser capable of peak intensities of tens of terawatts (TW; 1 TW = 10(12) watts [W]) per square centimeter. Rat skin was exposed in vitro to femtosecond-pulsed Ti:Al2O3 laser radiation at 800 nm, while varying the number of pulses and the intensity up to 46 TW/cm2. Ablation was evaluated by monitoring the amount of tissue removed per pulse as a function of energy, and by light microscopic examination of damage to adjacent, nonirradiated tissue. OBSERVATIONS: Ablation depth per pulse was 0.1 micron at threshold intensity, and it was increased with both the energy per pulse and the number of pulses. Minimal damage to adjacent healthy tissue was observed, varying 0 to 30 microns. CONCLUSION: The results suggest that ablation of skin with femtosecond-pulsed, terawatt Ti:Al2O3 laser may have potential for precision cutaneous surgery, and in vivo studies are indicated. PMID- 8352624 TI - Pattern of familial aggregation of vitiligo. AB - BACKGROUND AND DESIGN: Vitiligo is a disorder whose cause is not well understood. This study was undertaken to clarify whether genetic factors are involved in the pathogenesis of vitiligo. Data on 160 white kindreds living in the United States have been collected. Each family was ascertained through a proband afflicted with vitiligo. The nature and extent of familial aggregation and other relevant epidemiologic features have been determined. RESULTS: The mean age at onset of vitiligo is about 19 years in male and about 24 years in female individuals. The percentage of probands reporting one or more first-degree relatives also afflicted with vitiligo is 20%. Children of probands are found to be afflicted about 1.7 times more commonly than other first-degree relatives. The relative risk (RR) for vitiligo is about 7 for parents, about 12 for siblings, and about 36 for children. For second-degree relatives, the RR varies between 1 and 16. Relative risks for all first- and second-degree relatives, except uncles and grandsons, are significant at the 5% level. In families in which one or more relatives of the proband are afflicted with vitiligo, the intrafamilial correlation of ages at onset of vitiligo is moderate (0.6). No statistically significant effect (at the 5% level) of parental age at first childbirth was seen on the proportion of offspring afflicted with vitiligo. No significant association of some commonly related diseases (eg, thyroid disorder or alopecia areata) was observed with vitiligo or with a family history of vitiligo. CONCLUSIONS: The extent of familial aggregation of vitiligo is statistically significant. The pattern of relationship between RR and degree of kinship indicates involvement of genetic factors, although it is not consistent with single-locus mendelian transmission. PMID- 8352626 TI - 1992-1993 national directory of certified nephrology nurses. PMID- 8352627 TI - American Nephrology Nurses' Association position statement. HIV and HIV related illness. PMID- 8352625 TI - A multicenter study on the use of pulsed low-intensity direct current for healing chronic stage II and stage III decubitus ulcers. AB - BACKGROUND AND DESIGN: Pulsed low-intensity direct current (300 to 600 microA) has been used in a double-blind placebo multicenter study in the treatment of stage II and stage III chronic decubitus ulcers. RESULTS: Seventy-four ulcers were treated in four centers. Forty-three patients were selected for the experimental group, and 31 control subjects used the sham instrument (placebo group). In the treated group, 25 ulcers (58%) healed in 8 weeks, whereas in the placebo group, only one ulcer (3%) healed and most ulcers increased in size. Statistical analysis, based on surface area and ulcer depth before and after treatment, showed that low-intensity direct current had a significant influence on the healing rates for these ulcers (P < .0001). Experiments with guinea pigs (n = 10) showed that pulsed low-intensity direct current caused a rapid calcium flux in the epidermis. CONCLUSIONS: Pulsed low-intensity direct current represents a useful approach for the treatment of stage II and stage III chronic decubitus ulcers by increasing the healing rate. The growth of fibroblasts and keratinocytes may be enhanced by pulsed low-intensity direct current due to changes in calcium homeostasis. PMID- 8352628 TI - Hemodialysis of the infant or small child with chronic renal failure. AB - Hemodialysis of the infant or small child with chronic renal failure is often considered technically difficult or impossible. At Children's Hospital, however, chronic hemodialysis has proved to be safe and effective, and a vital component in the overall care of these complex patients. Although the ultimate goal is renal transplantation, chronic hemodialysis can provide an excellent primary or alternative treatment when peritoneal dialysis has failed or is not an option. PMID- 8352629 TI - Living with renal failure. AB - In this interpretive study, the experience of patients living with chronic renal failure was studied. Within the framework of Heideggerian phenomenology, a hermeneutic analysis revealed three themes and one constitutive pattern. The three themes were: taking on a new understanding of Being, maintaining hope and dwelling in dialysis. The constitutive pattern was " CONTROL: The Meaning of Technology." The findings provide an understanding of living with renal failure that argues against the traditional understanding of noncompliant behaviors. The study makes visible the meaning of technology in the lives of renal patients and highlights the need for nurses to sustain meaningful human connections with patients. PMID- 8352630 TI - Home visit effectiveness for peritoneal dialysis patients. AB - Medicare regulations require follow-up home visits to home dialysis patients, yet routine home visits require a lot of personnel time. The effectiveness of home visits was evaluated by a nurse, dietitian and social worker using a questionnaire. Thirty-six patients were evaluated during an 18-month period. Collectively the team documented an average of 10 pertinent observations per visit and made an average of 4 recommendations for change. Staff members gained new information about the patient as indicated by the fact that they changed their rankings on 5 of 15 parameters following the home visit. The home visit policy that recommended an annual home visit was revised to recommend a single home visit for each new peritoneal dialysis patient. Further visits are performed only if significant problems are identified. PMID- 8352631 TI - End stage renal disease secondary to vasculitis. PMID- 8352632 TI - Case management of the anemic patient: epoetin alfa--focus on cognitive function. AB - Impaired cognitive function associated with end-stage renal disease (ESRD) can adversely affect a patient's quality of life and is only partially reversed by dialysis. Correction of anemia with Epoetin alfa improves cognitive function and other factors that affect quality of life. Thus, nephrology nurses can improve their patients' quality of life by ensuring adequate dosing of Epoetin alfa so that anemia is corrected and cognitive function benefits are achieved. In addition, a knowledge of how cognitive function is evaluated helps nurses analyze research studies related to this area. PMID- 8352633 TI - ANNA special interest groups. PMID- 8352634 TI - When is it teaching and when is it nagging? PMID- 8352635 TI - [Revascularization of extracranial cerebral arteries]. PMID- 8352636 TI - Effect of ethanol on pancreatic lysosomes in rats: a possible mechanism for alcoholic pancreatitis. AB - Four-hour infusion of ethanol (0.5 g/kg.hr) and additional 2-hour infusion of caerulein (0.2 microgram/kg.hr) and secretin (0.2 CU/kg.hr) caused hyperamylasemia, pancreatic edema and pancreatic histological changes such as interstitial edema and acinar cell vacuolization in the rat. Such a combined treatment also induced a redistribution of lysosomal enzyme cathepsin B, from the lysosomal fraction to the zymogen fraction in subcellular fractionation. Only ethanol infusion caused marginal changes in all these parameters. Moreover, 4 hour pre-infusion of ethanol caused a significant increase in pancreatic cathepsin B output stimulated by caerulein (0.2 microgram/kg.hr) and secretin (0.2 CU/kg.hr) compared with the control rats. This pretreatment of ethanol also caused a significant increase in cathepsin B/amylase output ratio. These results indicate that ethanol administration, if combined with exocrine stimulation, causes a colocalization of lysosomal hydrolases with digestive enzymes in the same subcellular compartment as well as in the pancreatic ductal space, and also suggest one possible mechanism for alcoholic pancreatitis both within and outside the acinar cells, since cathepsin B can activate trypsinogen. PMID- 8352637 TI - Heat shock response for ischemic kidney preservation and transplantation. AB - The heat shock response (HSR) is a form of stress conditioning during which reversible changes in cellular metabolism are rapidly induced by brief exposure to supra-physiologic levels of heat. The nature of these adaptive adjustments has been widely investigated and has received much attention in molecular biology and cancer research. Recent evidence indicates that a basic form of this stress response exists at the cellular level of virtually every organism. Although the physiological phenomenon of HSR is complex, it is well known that it can induce specific proteins, known as heat shock proteins (HSP's), which are not normally synthesized. HSP's become the major proteins synthesized during the heat shock response while normal protein synthesis is suppressed. In addition, the HSR has been demonstrated to confer a transient resistance to the organism to subsequent episodes of stress. Recently it has been reported that the HSR confers protection against cold ischemic injury and extends the cold preservation time of the rat kidney to 48 hours. In this study, we have applied the concept of HSR to the preservation, and transplantation of warm ischemically injured pig kidneys. Since there is a serious shortage of cadaver kidneys available for transplantation worldwide, this number would increase if warm ischemic kidneys could be utilized. However with present methods of organ recovery and preservation, such kidneys are not likely to function after transplantation even if they were removed. We hypothesized that the application of a thermal stress to pig kidneys prior to organ procurement and preservation will enhance the organs' ability to function after warm ischemic injury. PMID- 8352638 TI - A new experimental model for gallstone pancreatitis: short-termed pancreatico biliary duct obstruction and exocrine stimulation with systemic hypotension in rats. AB - The effects of short-termed (2 hours) obstruction of pancreatico-biliary duct (PBDO) and exocrine stimulation (IDH) by caerulein infusion (0.2 microgram/kg.hr) with systemic hypotension (SH) (30% reduction of mean arterial pressure for 30 min) on the exocrine pancreas were evaluated in the rat. PBDO and IDH with SH caused more significant rises in portal serum amylase, cathepsin B and malate dehydrogenase levels, and pancreatic water content as well as more significant redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction in the subcellular fractionations than only PBDO, or PBDO with IDH, or PBDO with SH group. In addition, more accelerated lysosomal and mitochondrial fragility were observed in the PBDO and IDH with SH group. Moreover, PBDO and IDH with SH caused an activation of larger amount of trypsinogen in the pancreas compared with other groups (PBDO with IDH and PBDO with SH group). These results indicate that present model of short-termed PBDO and exocrine stimulation with systemic hypotension seems to be pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries by PBDO, particularly with exocrine stimulation and pancreatic ischaemia, probably via activation of trypsinogen to trypsin by lysosomal enzyme such as cathepsin B. PMID- 8352639 TI - [Experimental study on reversibility of neuronal function in rats with congenital hydrocephalus]. AB - To evaluate the usefulness of cerebral evoked potential examination in determining the severity of hydrocephalus and its prognosis, we measured brainstem auditory evoked potential (BAEP), somatosensory evoked potential (SEP), and visual evoked potential (VEP) in rats with HTX congenital hydrocephalus. In addition, changes in cerebral evoked potentials were measured before and after shunt operation, and the reversibility of neuronal function was evaluated. In control rats without hydrocephalus, SEP appeared in the latter half of the first week after birth, and VEP and BAEP in the former half of the second week. The peak latency tended to gradually decrease with growth. Significant differences were observed in SEP in the latter half of the second week after birth and in VEP in the former half of the third week between the group with hydrocephalus and the control group. However, BAEP did not significantly differ between the two groups. These results suggest that impairment of cerebral function is more marked than that of brainstem function in rats with HTX congenital hydrocephalus, and SEP is the most useful for evaluating the progression of this disease. Ventriculo peritoneal shunt was performed in the rats with hydrocephalus in the latter half of the second week, when the N1 latency of SEP began to be prolonged, or in the latter half of the third week. Outcomes markedly differed between the two groups. However, the N1 latency of postoperative SEP was shortened in both groups. These results strongly suggest that the reversibility of neuronal function in hydrocephalus evaluated by SEP examination is well preserved until the terminal stage. Cerebral evoked potential examination, especially, SEP examination may be useful for evaluating the degree of impairment in neuronal function in hydrocephalus. PMID- 8352640 TI - [Murder of children by children and adolescents--a rare crime]. AB - Nine case reports obtained from the autopsy material of three German institutes of forensic medicine are presented to illustrate the rare offense "killing of a child by a child" and compared with data from the criminal statistics of the police. In addition, age-specific peculiarities, including adolescence, are also discussed. PMID- 8352641 TI - [The effect of luminous and signal munitions on the human body]. PMID- 8352642 TI - [Abortion in Japan]. AB - In Japan, the artificial abortion is a penal offence; only in the presence of certain conditions it is authorized under the provision of the Eugenic Protection Law which was promulgated in 1948. According to the law, the artificial abortion is restricted to the period, in which the fetus is not viable outside of the uterus. This period is prescribed by notification from the Ministry of Public Welfare; up to now it has been shortened twice (1976, 1991). Due to the introduction of economic reasons in the list of conditions and the simplification of the procedure the artificial abortion in Japan was virtually liberalized. Prosecution for illegal abortion is very rare in recent years. The number of reported artificial abortions decreases; in the about last 30 years it reduced by half. However, the increase in the number of abortions in women younger than 20 years of age is a problem. The abortion in teenagers is late compared with that in other age groups. Although the number of neonaticides does not seem to increase, the increase in the number of abortions in teenagers remains a serious problem in Japan. PMID- 8352643 TI - Function of methylcobalamin: coenzyme M methyltransferase isoenzyme II in Methanosarcina barkeri. AB - Methanosarcina barkeri was recently shown to contain two cytoplasmic isoenzymes of methylcobalamin: coenzyme M methyltransferase (methyltransferase 2). Isoenzyme I predominated in methanol-grown cells and isoenzyme II in acetate-grown cells. It was therefore suggested that isoenzyme I functions in methanogenesis from methanol and isoenzyme II in methanogenesis from acetate. We report here that cells of M. barkeri grown on trimethylamine, H2/CO2, or acetate contain mainly isoenzyme II. These cells were found to have in common that they can catalyze the formation of methane from trimethylamine and H2, whereas only acetate-grown cells can mediate the formation of methane from acetate. Methanol-grown cells, which contained only low concentrations of isoenzyme II, were unable to mediate the formation of methane from both trimethylamine and acetate. These and other results suggest that isoenzyme II (i) is employed for methane formation from trimethylamine rather than from acetate, (ii) is constitutively expressed rather than trimethylamine-induced, and (iii) is repressed by methanol. The constitutive expression of isoenzyme II in acetate-grown M. barkeri can explain its presence in these cells. The N-terminal amino acid sequences of isoenzyme I and isoenzyme II were analyzed and found to be only 55% similar. PMID- 8352644 TI - Analysis of a pleiotropic gene region involved in formation of catalytically active hydrogenases in Alcaligenes eutrophus H16. AB - In Alcaligenes eutrophus H16 a pleiotropic DNA-region is involved in formation of catalytically active hydrogenases. This region lies within the hydrogenase gene cluster of megaplasmid pHG1. Nucleotide sequence determination revealed five open reading frames with significant amino acid homology to the products of the hyp operon of Escherichia coli and other hydrogenase-related gene products of diverse organisms. Mutants of A. eutrophus H16 carrying Tn5 insertions in two genes (hypB and hypD) lacked catalytic activity of both soluble (SH) and membrane-bound (MBH) hydrogenase. Immunological analysis showed that the mutants contained SH- and MBH specific antigen. Growing the cells in the presence of 63Ni2+ yielded significantly lower nickel accumulation rates of the mutant strains compared to the wild-type. Analysis of partially purified SH showed only traces of nickel in the mutant protein suggesting that the gene products of the pleiotropic region are involved in the supply and/or incorporation of nickel into the two hydrogenases of A. eutrophus. PMID- 8352645 TI - Purification and characterization of phenylacetate-coenzyme A ligase from a denitrifying Pseudomonas sp., an enzyme involved in the anaerobic degradation of phenylacetate. AB - The enzyme catalysing the first step in the anaerobic degradation pathway of phenylacetate was purified from a denitrifying Pseudomonas strain KB 740. It catalyses the reaction phenylacetate + CoA + ATP-->phenylacetyl-CoA + AMP + PPi and requires Mg2+. Phenylacetate-CoA ligase (AMP forming) was found in cells grown anaerobically with phenylacetate and nitrate. Maximal specific enzyme activity was 0.048 mumol min-1 x mg-1 protein in the mid-exponential growth phase. After 640-fold purification with 18% yield, a specific activity of 24.4 mumol min-1 mg-1 protein was achieved. The enzyme is a single polypeptide with Mr of 52 +/- 2 kDa. The purified enzyme shows high specificity towards the aromatic inducer substrate phenylacetate and uses ATP preferentially; Mn2+ can substitute for Mg2+. The apparent Km values for phenylacetate, CoA, and ATP are 60, 150, and 290 microM, respectively. The soluble enzyme has an optimum pH of 8.5, is insensitive to oxygen, but is rather labile and requires the presence of glycerol and/or phenylacetate for stabilization. The N-terminal amino acid sequence showed no homology to other reported CoA-ligases. The expression of the enzyme was studied by immunodetection. It is present in cells grown anaerobically with phenylacetate, but not with mandelate, phenylglyoxylate, benzoate; small amounts were detected in cells grown aerobically with phenylacetate. PMID- 8352646 TI - Anaerobic oxidation of phenylacetate and 4-hydroxyphenylacetate to benzoyl coenzyme A and CO2 in denitrifying Pseudomonas sp. Evidence for an alpha oxidation mechanism. AB - Anaerobic degradation of (4-hydroxy)phenylacetate in denitrifying Pseudomonas sp. was investigated. Evidence is presented for alpha-oxidation of the coenzyme A (CoA)-activated carboxymethyl side chain, a reaction which has not been described. The C6-C2 compounds are degraded to benzoyl-CoA and furtheron to CO2 via the following intermediates: Phenylacetyl-CoA, phenylglyoxylate, benzoyl-CoA plus CO2; 4-hydroxyphenylacetyl-CoA, 4-hydroxyphenylglyoxylate, 4-hydroxybenzoyl CoA plus CO2, benzoyl-CoA. Trace amounts of mandelate possibly derived from mandelyl-CoA were detected during phenylacetate degradation in vitro. The reactions are catalyzed by (i) phenylacetate-CoA ligase which converts phenylacetate to phenylacetyl-CoA and by a second enzyme for 4 hydroxyphenylacetate; (ii) a (4-hydroxy)-phenylacetyl-CoA dehydrogenase system which oxidizes phenylacetyl-CoA to (4-hydroxy)phenylglyoxylate plus CoA; and (iii) (4-hydroxy)phenylglyoxylate: acceptor oxidoreductase (CoA acylating) which catalyzes the oxidative decarboxylation of (4-hydroxy)phenylglyoxylate to (4 hydroxy)benzoyl-CoA and CO2. (iv) The degradation of 4-hydroxyphenylacetate in addition requires the reductive dehydroxylation of 4-hydroxybenzoyl-CoA to benzoyl-CoA, catalyzed by 4-hydroxybenzoyl-CoA reductase (dehydroxylating). The whole cell regulation of these enzyme activities supports the proposed pathway. An ionic mechanism for anaerobic alpha-oxidation of the CoA-activated carboxymethyl side chain is proposed. PMID- 8352647 TI - Nitrogen regulation of lignin peroxidase and manganese-dependent peroxidase production is independent of carbon and manganese regulation in Phanerochaete chrysosporium. AB - In this study, a N-deregulated mutant (der8-5) of Phanerochaete chrysosporium was used as a tool to investigate the interrelationships between N, C, and Mn(II) regulation of LIP and MNP production in this organism. The results showed that LIP and MNP production by der8-5 was blocked in excess C medium but not in excess N medium. Furthermore, LIP and MNP production in this organism was subject to Mn(II) regulation regardless of the fact whether it is grown in low N medium or in high N medium. These and other results indicate that N regulation of LIP and MNP production in P. chrysosporium is independent of C and Mn(II) regulation. PMID- 8352649 TI - Pyranosone dehydratase from the basidiomycete Phanerochaete chrysosporium: improved purification, and identification of 6-deoxy-D-glucosone and D-xylosone reaction products. AB - Pyranose oxidase and pyranosone dehydratase (aldos-2-ulose dehydratase), enzymes which convert in coupled reactions D-glucose to beta-pyrone cortalcerone, peaked coincidently during idiophasic growth of Phanerochaete chrysosporium under agitated conditions. The enzymes were purified from mycelial extracts of the fungus and separated from each other by hydrophobic interaction chromatography on Phenyl-Sepharose and Phenyl-Superose. Two pyranosone dehydratase activity peaks, PD I and PD II, were resolved. The major PD I fraction, consisting about 74% of the total dehydratase activity, was further purified by anion exchange chromatography on Mono Q to yield apparently pure enzyme as judged by SDS-PAGE and gel filtration on Superose 12. Isoelectric focusing indicated microheterogeneity of the protein by the presence of at least five protein bands with pI 5.1-5.3. PD II had a pI of 5.75. Overall PD I purification was 60.7-fold with 50% yield. The enzyme acted on several osones (glycosuloses), with the preferred substrate being D-glucosone. D-Xylosone and 6-deoxy-D-glucosone were dehydrated at C-3-C-4 to give the corresponding 5-hydroxy-2,3-dioxoalcanals (4 deoxy-2,3-glycosdiuloses), new enzymatically produced sugar derivatives. The latter labile compounds were trapped as diphenylhydrazine or o-phenylenediamine derivatives and spectroscopically identified. The analogous D-glucosone dehydration product did not accumulate due to its further transformation. pH optimum of PD I activity was 6.0 and its pH stability was optimal at pH 7-11. The enzyme was sensitive to Me2+ chelating agents and some heavy metal ions (Hg2+, Cu2+). PMID- 8352650 TI - Expression of hydrogenase in Hupc strains of Bradyrhizobium japonicum. AB - Plasmid-borne hup-lacZ transcriptional fusion constructs were introduced into three separate mutant strains of Bradyrhizobium japonicum which express hydrogenase constitutively (Hupc strains SR470, SR473 and JH101) in both autotrophic and heterotrophic environments. The lacZ structural gene linked directly to the regulatory region upstream of the hydrogenase structural gene encompassing -149 bases expressed beta-gal at a constant, high level, in response to various concentrations of Ni (0 microM to 1 microM). beta-Gal activity was expressed at a constant level in response to variations in concentration of O2 (0%-10%) and H2 (0%-10%) as well. The cis-acting region required to express hydrogenase constitutively is located between -149 and -98 bases. This is also the site of nickel, oxygen and hydrogen-dependent regulatory action in the wild type strain. It is postulated that a single mutation in Hupc strains affects the trans-acting factor which would normally by responsive to Ni, O2 and H2. PMID- 8352648 TI - Copper-containing nitrite reductase from Pseudomonas aureofaciens is functional in a mutationally cytochrome cd1-free background (NirS-) of Pseudomonas stutzeri. AB - The structural gene, nirK, for the respiratory Cu-containing nitrite reductase from denitrifying Pseudomonas aureofaciens was isolated and sequenced. It encodes a polypeptide of 363 amino acids including a signal peptide of 24 amino acids for protein export. The sequence showed 63.8% positional identity with the amino acid sequence of "Achromobacter cycloclastes" nitrite reductase. Ligands for the blue, type I Cu-binding site and for a putative type-II site were identified. The nirK gene was transferred to the mutant MK202 of P. stutzeri which lacks cytochrome cd1 nitrite reductase due to a transposon Tn5 insertion in its structural gene, nirS. The heterologous enzyme was active in vitro and in vivo in this background and restored the mutationally interrupted denitrification pathway. Transfer of nirK to Escherichia coli resulted in an active nitrite reductase in vitro. Expression of the nirS gene from P. stutzeri in P. aureofaciens and E. coli led to nonfunctional gene products. Nitrite reductase activity of cell extract from either bacterium could be reconstituted by addition of heme d1, indicating that both heterologous hosts synthesized a cytochrome cd1 without the d1-group. PMID- 8352651 TI - Characterization of the glyceraldehyde 3-phosphate dehydrogenase from the extremely halophilic archaebacterium Haloarcula vallismortis. AB - Glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) from the extremely halophilic archaebacterium Haloarcula vallismortis has been purified in a four step procedure to electrophoretic homogeneity. The enzyme is a tetramer with a relative molecular mass of 160,000. It is strictly NAD(+)-dependent and exhibits its highest activity in 2 mol/l KCl at 45 degrees C. Amino acid analysis and isoelectric focusing indicate an excess of acidic amino acids. Two parts of the primary sequence are reported. These peptides have been compared with glyceraldehyde 3-phosphate dehydrogenases from other archaebacteria, eubacteria and eucaryotes. The peptides show a high grade of similarity to glyceraldehyde 3 phosphate dehydrogenase from eucaryotes. PMID- 8352652 TI - Identification of the nifJ gene coding for pyruvate: ferredoxin oxidoreductase in dinitrogen-fixing cyanobacteria. AB - A 329 bp DNA segment from both Anabaena variabilis and Anabaena PCC 7119 was amplified using the polymerase chain reaction (PCR). The sequences from the two cyanobacteria showed strong similarities to the corresponding part of the nifJ gene from Klebsiella pneumoniae and Enterobacter agglomerans. The present findings underline earlier results of enzymatic studies that heterocystous cyanobacteria possess a pyruvate:ferredoxin (flavodoxin) oxidoreductase (PFO). The nifJ gene segment could not be detected in the non-dinitrogen-fixing, unicellular cyanobacterium Anacystis nidulans which is also in accord with previous findings from enzyme assays. PMID- 8352654 TI - PCR detection of the sheep-associated agent of malignant catarrhal fever. AB - From a genomic library previously constructed from a lymphoblastoid cell line (LCL) propagated from a bovine case of sheep-associated malignant catarrhal fever (SA-MCF), caused by ovine herpesvirus-2 (OHV-2), several OHV-2 clones were identified and characterised by hybridisation using probes from the unique region of the Alcelaphine herpesvirus-1 (AVH-1) genome. Nucleotide sequence from one clone was generated and the predicted amino acid sequence was found to contain regions of homology with the 140 and 160 kDa tegument proteins of Epstein-Barr virus and herpesvirus saimiri respectively. Oligonucleotide primers were constructed and a polymerase chain reaction (PCR) test was developed for the detection of OHV-2 viral DNA. Amplified product was identified by restriction with RsaI and BmyI. The primers were highly specific for OHV-2 DNA with a limit of detection of 6.4 pg of genomic DNA derived from the parent LCL. This was estimated to correspond to one diploid bovine cell. The PCR was successfully applied to detect OHV-2 DNA in peripheral blood leucocytes (pbl) from clinical cases of SA-MCF and normal sheep. PMID- 8352655 TI - Nucleotide sequence of the capsid protein cistrons from six potato virus Y (PVY) isolates infecting tobacco. AB - Complementary DNA libraries representing the capsid protein cistron of the potato virus Y (PVY) isolate 'Chilean', 'Hungarian', MsNr, NsNr, O, and 'Potato US' were synthesized and used as template for polymerase chain reaction (PCR) amplification. An AUG codon for initiating a discrete capsid protein (CP) open reading frame was embedded upstream of the first codon of the CP cistrons. PCR amplified products of the expected size of 0.8 kilo bases were cloned into the transcription vector pBS(+). The fidelity of each PCR-amplified PVY CP cistron was tested by transcribing recombinant plasmids in vitro and translating the transcripts in two cell free translation systems. Translation analysis of in vitro transcribed PVY CP cistrons consistently yielded a polypeptide co-migrating with authentic CP that was immunoprecipitated by anti PVY 'Chilean' antibodies. The nucleotide sequence of each capsid protein gene was determined by dideoxy sequence analysis. Each capsid protein gene was determined to be 801 nucleotides in length, encoding a deduced protein of 267 amino acids with calculated M(r) ranging from 29,799 to 29,980. The nucleic acid sequence similarity between the six isolates ranged between 89 to 97% and the amino acid similarity between 91 to 99%. The high level of amino acid sequence similarity confirms the classification of these viruses as isolates of PVY. PMID- 8352656 TI - Complete nucleotide sequence of sugarcane streak Monogeminivirus. AB - The complete nucleotide sequence of the genome of the Monogeminivirus sugarcane streak virus (SSV) was determined from cloned replicative form DNA. The genome is contained in one DNA circle of 2,758 nucleotides, and has four open reading frames with the potential to encode proteins of MW > 10 kDa: two in the viral (+) sense and two in the complementary (-) sense. Each open reading frame has a counterpart among the open reading frames reported for other Monogeminiviruses. A potential binding site for a DNA replication primer and potential transcriptional control sequences were identified on the (+) strand, and a possible intron on the (-) strand. Phylogenetic analysis of coat protein and replication-associated protein sequences of SSV and other grass-infecting geminiviruses indicate that SSV, although distinct from any other virus, is part of an "African streak virus subgroup" of Monogeminiviruses. PMID- 8352658 TI - Geminivirus nomenclature: the need to set taxonomic standards. AB - The geminiviruses are plant viruses of significant economic impact. Different nomenclature has been used in various studies in descriptions of their genomes. We propose in this communication a uniform nomenclature to be used in future studies. PMID- 8352657 TI - Subgroup F adenovirus growth in foetal intestinal organ cultures. AB - An in vitro foetal intestinal organ culture system was employed to determine the permissiveness of human intestinal cells for subgroup F adenovirus infection. Ad40 and Ad41 growth, monitored through group-specific hexon antigen production, was poor in comparison to that of Ad2 in these cultures, further demonstrating their fastidious nature in most human cells. The low growth capability of these viruses in culture, in relation to their association with gastrointestinal disease is discussed. PMID- 8352653 TI - Role of Langerhans cells and other dendritic cells in viral diseases. AB - Langerhans cells are part of a vast system of potent antigen-presenting cells known under the name of dendritic cells. During the last decade, much has been learned on dendritic cell involvement in the immune response to infectious diseases. This review briefly summarizes our current understanding of the role played by Langerhans cells and other dendritic cells in the pathogenesis of DNA and RNA virus infections. These data may form the basis for the development of innovative approaches in the diagnosis, prevention, and treatment of viral diseases. PMID- 8352661 TI - Coexisting migraine and tension-type headache. PMID- 8352659 TI - Resistance of mice vaccinated with rabies virus internal structural proteins to lethal infection. AB - Mice were vaccinated with recombinant vaccinia virus (rVac) expressing the glycoprotein (G), nucleoprotein (N), phosphoprotein (NS) or matrix protein (M) of rabies virus and their resistance to peripheral lethal infection with street rabies virus was examined. Mice vaccinated with rVac-G or rVac-N developed strong antibody responses to the corresponding proteins and essentially all mice survived challenge infection. Mice vaccinated with rVac-NS or rVac-M developed only a slight antibody response, however, a significant protection (59%) was observed in the rVac-NS-vaccinated mice, whereas rVac-M-vaccinated mice were not protected. No anti-G antibodies were detected in the sera of mice which has been vaccinated with rVac-N or rVac-NS and survived challenge infection. Passive transfer of anti-N monoclonal antibodies (MAbs) recognizing an epitope located on amino acids 1-224 of the protein prior to challenge resulted in significant protection, although the protection was not complete even with a high amount of antibodies. In contrast, none of the mice given MAbs recognizing an epitope of amino acids 247-415 or F(ab')2 fragments from a protective MAb IgG were protected. Administration of anti-CD 8 MAb to rVac-N-vaccinated mice showed no significant effect on protection. Our observations suggest that a considerable part of the protection achieved by the vaccination with rVac-N can be ascribed to the intact anti-N antibodies recognizing an epitope located on amino acids 1-224 of the protein. PMID- 8352660 TI - RNA hybrid mismatch polymorphisms in Australian populations of turnip yellow mosaic tymovirus. AB - In the Mt. Kosciusko alpine area of Australia there are three well-separated populations of Cardamine lilacina, an endemic sward-forming perennial brassica, and these are infected with turnip yellow mosaic tymovirus. The genetic variation in these viral populations has been assessed by an RNA hybrid mismatch polymorphism method. About 100 isolates were examined; the genomic RNA of each isolate was prepared from a shoot of a single wild C. lilacina plant. RNA hybrid mismatch polymorphisms (RHMPs) were assessed in six regions of the genomes using labelled negative-strand probes transcribed from selected portions of a cloned TYMV genome. The probed region at the 3' end of the genome showed little variation and over 95% of the isolates gave the same pattern. However, other parts of the genome, including the 5' non-coding region, were much more variable. There was no significant correlation between groupings based on the RHMP patterns, and the location from which the isolates were collected, nor with the symptom type or severity shown by their host plants. The patterns of variation suggested that all three populations of the virus are a single quasi-species; at most one tenth of the isolates gave similar RHMP patterns, those of the "master copy". PMID- 8352662 TI - The origin of pain in 'ischemic-diabetic' third-nerve palsy. PMID- 8352663 TI - Unimpaired verbal memory and oculomotor control in asymptomatic adults with the genetic marker for Huntington's disease. AB - OBJECTIVE: To determine whether asymptomatic individuals at very high genetic risk for Huntington's disease (HD) have demonstrable cognitive or oculomotor abnormalities. DESIGN: A case-control study was employed. Presence of the chromosome-4 DNA marker linked to the HD phenotype was the criterion for HD risk. SETTING: The Baltimore Huntington's Disease Project Presymptomatic Testing Program at The Johns Hopkins University School of Medicine, Baltimore, Md. PARTICIPANTS: Seventy-six asymptomatic adults at risk for HD, voluntarily enrolled for genetic testing, and determined by clinical examination to be free of major psychiatric disorder or evidence of HD. Twenty were determined to be at greater than or equal to 95% risk for HD; 56 were at less than or equal to 5% risk [corrected]. MEASURES: The Hopkins Verbal Learning Test was used to assess verbal learning and memory. Oculomotor functioning was assessed using Novel Stimulus, Mirror-Stimulus, and Predictive-Saccade paradigms. Outcome measures included number of correctly recalled words, recognition accuracy, and response bias, as well as saccade latency and number of errors on the Mirror-Stimulus Test. RESULTS: With one exception, all participants performed within the normal range on the Hopkins Verbal Learning Test. In a blind follow-up examination of the individual who performed aberrantly on the Hopkins Verbal Learning Test, she exhibited neurologic and psychiatric changes sufficient for a clinical diagnosis of HD. There were no group differences on the tests of oculomotor functioning. CONCLUSIONS: Young, asymptomatic adults at very high genetic risk for HD are unimpaired in tests of verbal learning and memory and oculomotor functioning. PMID- 8352664 TI - Late-onset Friedreich's ataxia. Molecular genetics, clinical neurophysiology, and magnetic resonance imaging. AB - OBJECTIVE--To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA), ie, patients who have later onset of Friedreich's ataxia (FRDA), often after 25 years of age. DESIGN--Comparison of clinical examination data, nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging of a family with LOFA with a group of patients with FRDA. Genetic linkage analysis was performed in the family with LOFA. SETTING--Referral center. PATIENTS--Thirteen patients satisfied classic diagnostic criteria of FRDA, and three patients from one family satisfied all diagnostic criteria of FRDA but with disease onset after 25 years. RESULTS--Results of nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging in patients with LOFA closely corresponded to observations made in patients with FRDA. In addition, genetic linkage analysis using markers tightly linked to the FRDA locus on chromosome 9 showed that all affected members of the LOFA family, but not their unaffected siblings, had inherited identical paternal and maternal genotypes. CONCLUSIONS--Data suggest that LOFA may also result from mutation within the FRDA locus. PMID- 8352665 TI - Vitamin B12 deficiency and nervous system disease in HIV infection. AB - BACKGROUND: Vitamin B12 deficiency may result in a number of neurological and neuropsychiatric disorders. Patients with human immunodeficiency virus type 1 (HIV-1) infection may have a high rate of vitamin B12 deficiency and nervous system disease. Vitamin B12 deficiency may contribute to neurological disease in HIV-1-infected individuals. OBJECTIVE: To evaluate the possible contribution of vitamin B12 deficiency to neurological disease in HIV-1-infected individuals. MAIN OUTCOME MEASURES: Comparison of serum vitamin B12 levels with neurological, neuropsychological, and mood state abnormalities in 153 HIV-1-positive subjects and 57 high-risk seronegative controls. A subgroup of 67 subjects underwent additional extensive clinical neurophysiological, cerebrospinal fluid, and magnetic resonance imaging evaluations. RESULTS: No statistically significant relationships were noted between vitamin B12 levels and abnormalities on any of the measures examined. CONCLUSIONS: This study does not indicate an important role for vitamin B12 deficiency in the neurological disease of HIV-1 infection. PMID- 8352666 TI - Hippocampal neuron loss and memory scores before and after temporal lobe surgery for epilepsy. AB - OBJECTIVE: To assess the relationship of hippocampal neuron loss to intellectual and memory measures before and after temporal lobe surgery. DESIGN: Pyramidal cell loss, as determined on the resected tissue, of hippocampal subregion CA1 correlated highest with other subregional cell loss and thus was used as the primary indicator of hippocampal neuron loss. Groups of patients with left and right temporal lobe seizures were subdivided according to degree of CA1 neuron loss. Behavioral performances of patient groups were compared before and after surgery. SETTING: Patient data were obtained from a university program of surgery for epilepsy. CASES: Twenty-five patients who had intractable epilepsy. MAIN OUTCOME MEASURES: Wechsler Adult Intelligence Scale IQ scores, verbal and nonverbal memory measures adapted from the Wechsler Memory Scale, and the Rey Osterrieth recall score. RESULTS: Degree of hippocampal cell loss selectively related to learning of unrelated word pairs, both preoperatively and postoperatively, in patients with left but not right temporal lobe seizures. Patients with severe loss of left hippocampal neurons performed worse than those with mild-moderate neuron loss both before and after surgery. Immediate recall of logical prose did not relate to hippocampal neuron loss, although scores decreased following left temporal lobe surgery. CONCLUSION: These findings support a role for the left hippocampus in rote verbal memory, ie, learning of unrelated word pairs. Semantically complex verbal learning, ie, recall of logical prose, is more dependent on extrahippocampal temporal lobe regions. Finally, patients with severe as compared with minimal left hippocampal neuron loss may be at risk for lower memory functioning postoperatively. PMID- 8352667 TI - White matter changes in healthy elderly persons correlate with attention and speed of mental processing. AB - OBJECTIVE: To evaluate the association between white matter changes (leukoaraiosis [LA]) seen on magnetic resonance imaging and cognitive functions. DESIGN: Survey of cohorts of neurologically healthy elderly subjects derived consecutively from a population-based random sample. SETTING: General community, the Helsinki (Finland) Aging Brain Study. SUBJECTS: Cohorts of neurologically healthy subjects aged 55, 60, 65, 70, 75, 80, and 85 years (n = 20, 18, 19, 18, 17, 17 and 11 subjects, respectively; total N = 120). MEASURES: Leukoaraiosis was rated in the periventricular areas (0 to 24) and the centrum semiovale (0 to 24); also, a total LA score was obtained (0 to 48). The neuropsychological test battery covered memory, verbal intellectual and constructional functions, language, speed and attention, and speed of mental processing, as well as simple psychomotor speed. RESULTS: Low age-related LA scores and deterioration of cognitive functions were obtained in the normal subjects. When controlling for age, we found that speed and attention, together with the speed of mental processing measured by the Trail Making A and the Stroop tests, correlated with the total LA score. However, there was wide variation between subjects. Comparing groups with and without LA proved the association of LA with Trail Making A time, Stroop test result (words/time and difference/time), and the compound score of speed and attention. Presence of periventricular LA was especially related to speed of mental processing. CONCLUSION: Leukoaraiosis could explain some of the intellectual impairment in the elderly, especially that of slowing of distinct motor and attentional functions, as well as slowing of mental processing. Mild LA in normal aged subjects could also signal brain at risk for further cognitive impairment. PMID- 8352668 TI - Propranolol and amitriptyline in prophylaxis of migraine. Pharmacokinetic and therapeutic effects. AB - OBJECTIVES: To determine if the effectiveness of propranolol hydrochloride and amitriptyline hydrochloride are correlated with blood levels and/or with standardized test of pharmacologic effect and to determine which clinical variables are predictors of response to one or the other medication. DESIGN: Three-month modules of treatment with each drug and placebo in a randomized crossover design. Headache scores from daily diaries were calculated at monthly intervals, as were simultaneous blood levels of drug, supine and standing blood pressure, pulse rise with exercise, and salivary flow. SETTING: Outpatient headache clinic at the University of Kansas Medical Center, Kansas City. PATIENTS: Thirty consecutive patients with a history of frequent migraine. MAIN OUTCOME MEASUREMENTS: From headache scores, patients were classified as either propranolol responders, amitriptyline responders, or nonspecific responders. Clinical variables as predictors of response to medications were studied, as were effects on frequency, duration, and/or severity of headache. RESULTS AND CONCLUSIONS: No significant correlations were found between changes in headache score and blood level of drug or change in any of the physiologic measurements. Amitriptyline significantly reduced the severity, frequency, and duration of headache attacks; propranolol reduced the severity of attacks only. Amitriptyline response was correlated with female gender and baseline headaches of shortest duration and of highest frequency. Propranolol response was associated with attacks of greatest duration at baseline and with low pulse rise with exercise at baseline. Nonspecific response was associated with male gender and most frequent headaches by history. PMID- 8352670 TI - Myasthenic crisis. Response to plasmapheresis following failure of intravenous gamma-globulin. AB - Myasthenic crisis is a potentially life-threatening complication of myasthenia gravis that requires aggressive therapy. We describe four patients in whom myasthenic crisis developed and who failed to respond to initial treatment with intravenous gamma-globulin. All four patients subsequently responded to intensive plasma exchange. Based on our experience, plasmapheresis appears to be superior to intravenous gamma-globulin for the treatment of myasthenic crisis in certain patients. Prognostic factors that determine the effectiveness of intravenous gamma-globulin vs plasmapheresis in these patients merit further investigation. PMID- 8352669 TI - Factors that predict antiphospholipid immunoreactivity in young people with transient focal neurological events. AB - OBJECTIVE: To determine if clinical or radiological features in young people with transient focal neurological events may be used to predict the presence of antiphospholipid antibodies (aPL). DESIGN: A combined retrospective and prospective study of young people with transient focal neurological events. Likelihood ratios and confidence intervals were calculated for the proportions; logistic regression analysis was performed to determine features predictive of aPL immunoreactivity. SETTING: A referral hospital and adjacent outpatient clinic. PATIENTS: Sixty-eight patients with one or more transient focal neurological events were screened for aPL. Forty-seven patients were obtained retrospectively from medical record review of every outpatient personally seen by two of us (G.E.T. and S.R.L.) during a 4.5-year period. Twenty-one patients were prospectively added prior to retrospective analysis. Patients older than 50 years or those with multiple sclerosis or epilepsy were excluded. Five patients fulfilling study criteria were excluded because aPL assay results were unavailable. MAIN OUTCOME MEASURES: Transient neurological symptoms, stroke risk factors, occurrence of cerebral or ocular infarct or death, headache history, and serological and radiological studies were systematically obtained. RESULTS: There were 29 aPL-positive patients compared with 39 aPL-negative ones. Features that distinguished the aPL-positive group included more common monocular visual symptoms (38% vs 15%, P = .03), hemisensory symptoms (76% vs 41%, P = .004), and systemic lupus erythematosus (14% vs 0%, P = .03) and less common binocular visual symptoms (28% vs 51%, P = .05), accompanying headache (66% vs 87%, P = .03), and personal (48% vs 74%, P = .03) and family (29% vs 61%, P = .01) history of migraine. No differences were noted between the groups for age, gender, stroke risk factor profile, and radiological features. In a logistic regression analysis, the estimated odds ratio for aPL positivity in patients with monocular visual disturbance, hemisensory symptoms, and no family history of migraine were 5.3, 7.5, and 3.0, respectively, when controlling for the other variables. CONCLUSIONS: Several clinical features of transient focal neurological events in aPL-positive patients distinguish these individuals from their aPL-negative cohort. Amaurosis fugax, unilateral paresthesias, and no family history of migraine may predict aPL positivity in young persons with transient focal neurological deficits. PMID- 8352671 TI - Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group. AB - OBJECTIVE: Changes in the brain on magnetic resonance images are common in patients with optic neuritis even when there is no other clinical evidence of multiple sclerosis. The current study was designed to determine systematically the prevalence of brain abnormalities on magnetic resonance images in the patients entered into the Optic Neuritis Treatment Trial. DESIGN: Prospective multicenter clinical trial. SETTING: Referral centers. PATIENTS AND METHODS: Brain magnetic resonance images from 418 patients with acute optic neuritis (77% women; mean age, 32.0 years) were evaluated at a central reading center with the use of a standardized classification system (ranging from 0 for normal to IV for most extensive changes). RESULTS: Of the scans, 40.9% were classified as grade 0, 10.8% as grade I, 9.1% as grade II, 6.7% as grade III, and 32.5% as grade IV. For patients with isolated (monosymptomatic) optic neuritis, 26.7% had two or more lesions. CONCLUSIONS: We found a lower prevalence of brain magnetic resonance imaging abnormalities in isolated optic neuritis than previous studies have reported. This likely is due to our study having a higher degree of standardization of patient inclusion criteria, which limited patient selection bias. PMID- 8352672 TI - Anatomic-radiologic basis of Lhermitte's sign in multiple sclerosis. AB - OBJECTIVE: To test the presumption that Lhermitte's sign in multiple sclerosis is the result of a lesion in the cervical spinal cord. DESIGN: The radiologic files of 887 patients with multiple sclerosis were reviewed. A detailed questionnaire regarding Lhermitte's sign was sent to 75 patients who had undergone magnetic resonance imaging of the brain and cervical spinal cord. Of the 64 patients who responded, 55 patients who had complete magnetic resonance imaging files were studied. The cases of two illustrative patients are presented. RESULTS: A strong association between Lhermitte's sign and abnormalities of the cervical spinal cord seen on magnetic resonance imaging was noted. Most of the abnormalities were in the posterior part of the cervical spinal cord. CONCLUSIONS: The findings confirm the presumption that a lesion in the posterior columns of the cervical spinal cord is the cause of Lhermitte's sign in multiple sclerosis. PMID- 8352673 TI - Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography. AB - OBJECTIVE: To determine if previously hypertensive patients with acute ischemic stroke should be treated with antihypertensive medication in the immediate poststroke period. DESIGN: Randomized double-blind, placebo-controlled trial. SETTING: Sixteen consecutive hypertensive patients (four men and 12 women; mean age, 66 years [age range, 46 to 83 years]) with middle cerebral artery infarction within 72 hours of onset and blood pressure between 170 and 220 mm Hg(systolic) and 95 and 120 mm Hg (diastolic). INTERVENTION: Placebo (n = 6), nicardipine hydrochloride (20 mg [n = 5]), captopril (12.5 mg [n = 3]), or clonidine hydrochloride (0.1 mg [n = 2]) given every 8 hours for 3 days. MAIN OUTCOME MEASURES: Decline in blood pressure, change in cerebral blood flow as measured by single photon emission computed tomography, and clinical change as determined by the National Institutes of Health Stroke Scale. RESULTS: Blood pressure fell significantly in both the drug-treated group as a whole and in those patients receiving placebo (P < .001). There was no difference in blood pressure levels between these two groups throughout the study period. Patients receiving nicardipine had a consistently lower pressure than the other groups. A significant negative relationship was noted between the maximum blood pressure fall and improvement in cerebral blood flow. There were four patients whose blood pressure dropped by more than 16% of the baseline value on any 24 hours in the first 3 days. All either failed to increase or actually decreased their cerebral blood flow to the affected area. Three of these patients were treated with nicardipine. There was no significant difference in clinical course between the placebo-and drug-treated groups as a whole. CONCLUSIONS: Hypertensive ischemic stroke patients with a moderate elevation of blood pressure in the first few days may not require antihypertensive therapy. Nicardipine and possibly other calcium channel blockers may cause an excessive fall in blood pressure and impair cerebral blood flow in these patients and should therefore be used with caution. PMID- 8352674 TI - Neurologist's role in understanding violence. PMID- 8352675 TI - The neurological defense of violent crime. 'Insanity defense' retooled. PMID- 8352676 TI - Frontal-subcortical circuits and human behavior. AB - OBJECTIVE: This synthetic review was performed to demonstrate the utility of frontal-subcortical circuits in the explanation of a wide range of human behavioral disorders. DATA SOURCES: Reports of patients with degenerative disorders or focal lesions involving frontal lobe or linked subcortical structures were chosen from the English literature. Individual case reports and group investigations from peer-reviewed journals were evaluated. STUDY SELECTION: Studies were included if they described patient behavior in detail or reported pertinent neuropsy-chological findings and had compelling evidence of a disorder affecting frontal-subcortical circuits. DATA EXTRACTION: Information was used if the report from which it was taken met study selection criteria. DATA SYNTHESIS: Five parallel segregated circuits link the frontal lobe and subcortical structures. Clinical syndromes observed with frontal lobe injury are recapitulated with lesions of subcortical member structures of the circuits. Each prefrontal circuit has a signature behavioral syndrome: executive function deficits occur with lesions of the dorsolateral prefrontal circuit, disinhibition with lesions of the orbitofrontal circuit, and apathy with injury to the anterior cingulate circuit. Depression, mania, and obsessive-compulsive disorder may also be mediated by frontal-subcotical circuits. Movement disorders identify involvement of the basal ganglia component of frontal-subcortical circuits. CONCLUSIONS: Frontal-subcortical circuits mediate many aspects of human behavior. PMID- 8352677 TI - Topical diclofenac reduces pain following photorefractive keratectomy. PMID- 8352678 TI - Zinc and macular degeneration. PMID- 8352680 TI - Suprachoroidal hemorrhage following a Valsalva maneuver. PMID- 8352679 TI - Magnetic resonance images of eyelid anatomy. PMID- 8352681 TI - Intravenous epinephrine and acute macular neuroretinopathy. PMID- 8352683 TI - Ocular protrusion with contralateral jaw movement. PMID- 8352682 TI - Proptosis and periorbital edema due to diltiazem treatment. PMID- 8352684 TI - Preparing for managed competition. Utilization of ambulatory eye care visits to ophthalmologists. PMID- 8352685 TI - The Alcon Research Institute. A model for interaction between the pharmaceutical industry and academic medicine. PMID- 8352686 TI - The content and cost of cataract surgery. AB - Although more than 1 million cataract surgeries are performed annually in the United States, little is known about the frequency of use or cost of various services provided in connection with this procedure. To assess the frequency with which various ophthalmic, optometric, anesthesia, and medical services are provided in conjunction with cataract surgery and to estimate the cost to Medicare associated with those services, we analyzed 1985 through 1988 Medicare claims records of a nationally representative 5% sample of Medicare beneficiaries. The experience of 57,103 Medicare beneficiaries who underwent extracapsular cataract surgery in 1986 or 1987 that was not combined with another ophthalmologic procedure formed the basis of our analysis. Projections for current costs were performed using 1991 charges allowed by Medicare for physician services. We estimate that the median charge allowed by Medicare for a "typical" episode of cataract surgery in 1991 was approximately $2500. In addition to the $3.4 billion that Medicare spent in 1991 on such "typical" episodes, Medicare spent more than $39 million on miscellaneous "atypical" preoperative ophthalmologic tests, such as specular microscopy (14% of cases) and potential acuity testing (8% of cases), more than $7 million on postoperative ophthalmologic diagnostic tests, such as fluorescein angiography (3% of cases), and more than $18 million on perioperative medical services (most commonly electrocardiography and chest roentgenography). The major determinants of the cost to Medicare associated with cataract surgery are the rate of performance of cataract surgery and neodymium-YAG laser capsulotomy and the charges allowed for these procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352687 TI - Prediction of visual function in eyes with mild to moderate posterior pole residua of retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - OBJECTIVE: The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) assigned eyes with macular heterotopia to the "favorable" outcome category and eyes with retinal fold involving the macula to the "unfavorable" outcome category. This binary assignment did not agree well with measured visual acuity outcome. We tested the hypothesis that rating structural outcome on a continuum from less to more severe would improve prediction of visual acuity in eyes with macular heterotopia or retinal fold. DESIGN: Fundus photographs of the 69 eyes in the CRYO-ROP trial that had macular heterotopia (n = 55) or retinal fold (n = 14) at the 1-year follow-up were analyzed for severity of macular heterotopia, macular elevation, and pigmentary disturbances. Each physician author estimated each eye's predicted Snellen acuity, based on the photographic findings and clinical expertise. These results were compared with the grating acuity obtained at ages 1 and 3 1/2 years with the Teller Acuity Card procedure and with letter acuity obtained at age 3 1/2 years with the crowded HOTV test. PATIENTS: The 69 eyes were from 59 patients in the randomized portion of the CRYO ROP trial. RESULTS: Although eyes with retinal fold tended to have greater visual impairment than eyes with macular heterotopia, there was a wide variation in acuity in both groups, and physicians were unable to predict visual acuity from retinal appearance. CONCLUSION: The physician cannot reliably predict either grating acuity or letter acuity in eyes with macular heterotopia or macular fold due to retinopathy of prematurity. There is no substitute for periodic visual acuity testing in these eyes. PMID- 8352688 TI - Anterior stromal puncture. Immunohistochemical studies in human corneas. AB - OBJECTIVE: To investigate the mechanism of action of corneal anterior stromal puncture (ASP) in humans. DESIGN: Immunocytochemical techniques were used to localize fibronectin, type IV collagen, and laminin in human corneas with bullous keratopathy, some of which had undergone ASP. Corneal specimens were obtained from transplant procedures performed in a related clinical study. SETTING: Outpatients in private practice settings. PATIENTS: Nine patients with recurrent erosion secondary to bullous keratopathy who were judged to be poor candidates for keratoplasty. INTERVENTIONS: Anterior stromal puncture was performed on each patient using a standardized needle, and corneal transplants were performed on patients whose erosions did not resolve after ASP. PRIMARY OUTCOME MEASURES: Subjective comfort and slit-lamp verification of resolution of rupture of bullae and erosions in patients who underwent ASP; Nomarski differential interference contrast photography, immunohistochemical staining, and light microscopy were applied to the corneal specimens. RESULTS: All three matrix glycoproteins were observed in the epithelial basement membrane of normal corneas. In patients with bullous keratopathy who did not undergo ASP, the epithelial basement membrane of the cornea did not stain with antibodies against human fibronectin, type IV collagen, or laminin. In patients with bullous keratopathy who underwent ASP, all three major proteins were present at the puncture sites and in the reactive subepithelial pannus adjacent to the puncture site. Epithelial basement membrane of untreated regions showed little or no staining. CONCLUSIONS: The results suggest that the absence of these extracellular matrix proteins in the epithelial basement membrane of patients with bullous keratopathy may be an important factor in the development of poor epithelial adhesion and secondary erosions. Anterior stromal puncture may promote epithelial reattachment, at least in bullous keratopathy, by stimulating the production of extracellular matrix proteins that are important in the attachment of epithelial cells to the underlying connective tissue. Epithelial-stromal reactions and the development of subepithelial fibrosis may also play a role in reestablishing epithelial attachment. PMID- 8352689 TI - Comparison of diabetic retinopathy detection by clinical examinations and photograph gradings. Barbados (West Indies) Eye Study Group. AB - OBJECTIVE: To compare the use of clinical examination and fundus photograph gradings in detecting diabetic retinopathy in a population that includes persons with and without diabetes. DESIGN: Population-based epidemiologic study. SETTING: Sir Winston Scott Polyclinic, Bridgetown, Barbados, West Indies. PARTICIPANTS: Subset of a random sample of the country's population aged 40 to 86 years. RESULTS: Among 1168 black persons with fundus photograph evaluations, ophthalmologic examinations, diabetes history, and glycated hemoglobin data, 21% reported a history of diabetes; 9.5% had definite diabetes (glycated hemoglobin > 11.5%); and 13.3% had a diabetes history and glycated hemoglobin value less than or equal to 11.5%. The frequency of diabetic retinopathy in this group was 7.7% (90/1168) by clinical examination, 8.7% (102/1168) by photograph gradings, and 6.7% (78/1168) by both methods. CONCLUSIONS: These results suggest that in certain populations that include diabetics and nondiabetics, a clinical examination by an ophthalmologist will detect most cases of diabetic retinopathy identified by disc and macula photographs read by skilled graders. However, it will lead to an underestimate of prevalence. Staff availability and cost, issues not examined in this study, should determine which approach is selected. PMID- 8352690 TI - Improvement in visual function after displacement of the retinal elevations emanating from optic pits. AB - OBJECTIVE: To define the functional deficit that correlates with the inner layer separation and the outer layer detachment that have been observed in optic pit maculopathy and to determine the effect of a gas tamponade that compresses or displaces the two layers. DESIGN: The central visual field before and after a gas tamponade on the posterior pole were charted on a 1-m tangent screen and compared with the changes in the retina observed biomicroscopically and with stereophotography. SETTING: The gas operations were done at four hospitals in the New York, NY, area and one in Cleveland, Ohio. The retinal examinations, visual field testing, and stereoscopic photography for eight patients were done at The New York Hospital. The patient who lived in Cleveland was examined and photographed in Cleveland. PARTICIPANTS: Nine patients between the ages of 18 and 46 years with optic pit maculopathy. INTERVENTION: The patients were operated on by five retinal surgeons with a variety of procedures. Four patients had a vitrectomy and intraocular gas injected. Five patients had gas injected after external compression. Two patients had laser applied in conjunction with the intraocular injection. The gas tamponade was the unifying factor. RESULTS: The dense central scotoma in optic pit maculopathy relates to the outer layer detachment and displacement of it from the posterior pole yields an improvement in visual acuity. The inner layer separation persists centrally after a gas tamponade and continues to provide access for the flow of fluid from the pit. The scotoma that relates to the inner layer separation is mild and consistent with relatively good visual acuity. PMID- 8352691 TI - Surgical management of complications associated with X-linked retinoschisis. AB - OBJECTIVE: To evaluate the role of surgical intervention in cases with severe, vision-threatening complications of X-linked retinoschisis. DESIGN: A retrospective survey of consecutive patients with X-linked retinoschisis who underwent surgery at our institution during a 16-year period. SETTING: A tertiary care eye hospital. PATIENTS: Six eyes of four patients were identified. The mean age of the patients at the time of the first surgical procedure was 4.9 years (range, 18 months to 9 years). INTERVENTION: Scleral buckling procedure or pars plana vitrectomy. MAIN OUTCOME MEASURE: Surgical indications and long-term anatomic and visual outcome. RESULTS: Patients were initially operated on for rhegmatogenous retinal detachment (three eyes), exudative retinal detachment (one eye), and vitreous hemorrhage (two eyes). The surgical approach was scleral buckling for retinal detachment and vitrectomy for vitreous hemorrhage or proliferative vitreoretinopathy. Anatomic success and ambulatory vision (20/400 or better) was achieved in five of the six eyes with a mean follow-up of 3.8 years (range, 1 to 6 1/2 years). An average of 1.8 procedures per eye were performed. Two of the four eyes approached by primary scleral buckling eventually required vitrectomy. Proliferative vitreoretinopathy with retinal detachment was the major reason for reoperation. CONCLUSIONS: Surgery for X-linked retinoschisis associated retinal detachment and vitreous hemorrhage can yield favorable anatomic and functional results. Multiple operations and the use of advanced vitreoretinal techniques to manage proliferative vitreoretinopathy-related complications, however, were necessary for ultimate success in certain cases. PMID- 8352692 TI - Strabismus following implantation of Baerveldt drainage devices. AB - OBJECTIVE: To describe the clinical features of strabismus following implantation of a Baerveldt glaucoma seton. DESIGN: Case series of four patients with a minimum follow-up of 6 months. SETTING: Specialized glaucoma referral center at Bascom Palmer Eye Institute/Ann Bates Leach Eye Hospital, Miami, Fla. PATIENTS: Consecutive sample of four patients with persistent binocular diplopia following implantation of a 350-mm2 Baerveldt glaucoma seton in the superotemporal quadrant. RESULTS: Each patient presented with a characteristic pattern of either exotropia or hypertropia, or both. The deviation increased with gaze opposite the ipsilateral superior and lateral muscles and decreased in the field of action of the involved muscles. All patients demonstrated a convergence insufficiency type of exotropia. CONCLUSION: These patients presented with a similar type of restrictive strabismus. Proposed mechanisms include an increase in the length tension curve of the muscle induced by the underlying bleb and a posterior fixation effect as a result of scarring behind the implant. PMID- 8352693 TI - Subepithelial mucinous corneal dystrophy. Clinical and pathological correlations. AB - We describe a family with an unusual autosomal dominant anterior corneal dystrophy. The onset was characterized by frequent, recurrent corneal erosions in the first decade. This subsided during adolescence and was followed by progressive decreased vision. Slit-lamp examination revealed bilateral subepithelial opacities and haze, involving the entire cornea, but most dense centrally. Histopathological study revealed a subepithelial band of eosinophilic, periodic acid-Schiff-positive, alcian blue-positive, hyaluronidase-sensitive material anterior to Bowman's layer. Electron microscopy demonstrated subepithelial deposition of fine fibrillar material consistent with glycosaminoglycan. Immunohistochemical analysis indicated that the accumulated material contained a combination of chondroitin 4-sulfate and dermatan sulfate. This unique condition clinically resembled Grayson-Wilbrandt dystrophy, but differed histochemically. To our knowledge, this anterior corneal dystrophy has not previously been reported, and it is best described by the name "subepithelial mucinous corneal dystrophy." PMID- 8352694 TI - Tissue plasminogen activator and Staphylococcus epidermidis endophthalmitis. AB - OBJECTIVE: To determine whether intraocular administration of tissue plasminogen activator (tPA) speeds clearance of inflammatory debris or prevents fibroproliferative complications in an animal model of endophthalmitis. METHODS: Aphakic rabbits were given an intraocular dose of Staphylococcus epidermidis organisms known to cause moderate inflammation and to self-sterilize. They were then randomized to receive either tPA or saline injections 2 and 3 days after inoculation. All eyes were graded by one masked clinician seven times, 1 to 28 days after infection. Vitreous samples from selected eyes were cultured. RESULTS: Treated and control eyes were found to have no significant difference in inflammatory scores. Although the eyes treated with tPA had more retinal detachments and more positive cultures than control eyes, these numbers were not statistically significant (P = .44 to .71). CONCLUSION: Fibrinolysis with intraocular tPA does not accelerate clearance of inflammation nor decrease fibroproliferative complications in this animal model of endophthalmitis. PMID- 8352695 TI - Corneal surface morphology following excimer laser ablation with humidified gases. AB - OBJECTIVE: To compare the effects of blowing dry (nitrogen or helium) and humidified gases over the corneal surface during photorefractive keratectomy. METHODS: Excimer laser myopic ablations were performed on porcine eyes (10 per group) using humidified and dry nitrogen and helium gas under ambient conditions. Surface smoothness was quantified with light and electron microscopy. RESULTS: Corneas that were ablated using humidified gas were smooth and equivalent to those ablated under ambient conditions. Dry nitrogen and helium blowing resulted in increased surface irregularity evident on light and electron microscopy (P < .001). The pseudomembranes in the humidified gas and ambient air groups had fewer surface discontinuities than did those in the nonhumdified gas groups and appeared to have a thinner electron-dense surface layer. CONCLUSIONS: The blowing of humidified gas during excimer laser corneal ablation produces a smoother surface than does the blowing of dry gas and is comparable to that produced under ambient (no blowing) conditions. Maintaining corneal moisture is important in photorefractive keratectomy. If blowing gas is necessary to remove debris from the surface, the gas should be humidified. PMID- 8352696 TI - Adrenochrome deposit. PMID- 8352698 TI - Here's to your health? PMID- 8352697 TI - Transconjunctival entropion repair. AB - Involutional lower-eyelid entropion has three underlying correctable causes: eyelid laxity, overriding of the orbicularis oculi muscle, and attenuation of the lower-eyelid retractors. We describe a new technique for correcting this problem. A transconjunctival approach is used to advance or fortify the lower-eyelid retractors. The orbicularis oculi muscle can also be addressed through this approach. Combining this technique with lateral canthal resuspension anatomically corrects the entropion by addressing all three correctable causes. Transconjunctival blepharoplasty can also be performed in conjunction with this technique. Twenty-three eyelids of 18 patients successfully underwent this procedure. Six patients underwent simultaneous transconjunctival blepharoplasty. Follow-up ranged between 9 and 18 months. There were no postoperative recurrences, overcorrections, or lower-eyelid retraction. This approach yields a stable and definitive repair of involutional entropion with excellent postoperative cosmesis. PMID- 8352699 TI - Effect of lovastatin on serum lipid profile in the treatment of dyslipoproteinaemia in uraemic patients on continuous ambulatory peritoneal dialysis. AB - BACKGROUND: Dyslipoproteinaemia is an important risk factor for cardiovascular disease in uraemic patients on continuous ambulatory peritoneal dialysis (CAPD). Lovastatin is an HMG Coenzyme A reductase inhibitor which is useful in treating non-uraemic patients with hypercholesterolaemia. AIMS: We conducted a single blind cross-over study versus placebo in 10 CAPD patients to examine the effect of lovastatin (20-40 mg) on the serum lipid profile and its safety in uraemic patients. METHODS: Treatment phases were of eight weeks' duration. Each four weeks' measurements were made of serum total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C), Apolipoprotein A1 & B (Apo A1 & Apo B) and Lipoprotein (a). After eight weeks, lovastatin significantly reduced TC by 29% from 6.7 +/- 0.3 (mean +/- S.E.M.) to 4.8 +/- 0.1 mmol/L, LDL-C by 41% from 4.6 +/- 0.3 to 2.7 +/- 0.1 mmol/L and Apo B by 32% from 116 +/- 7 to 78 +/- 3 mg/dl (p < 0.01). HDL-C increased by 8% from 1.2 +/- 0.1 to 1.3 +/- 0.2 mmol/L after eight weeks' therapy (p < 0.05). TG decreased by 18% from 1.9 +/- 0.4 to 1.6 +/- 0.3 mmol/L (p < 0.05). There was no significant difference in changes of other lipid profiles between placebo and drug. No adverse effects of the drug were noted during treatment and the liver function and muscle enzymes were not significantly altered by either drug therapy or placebo. RESULTS: Lovastatin appears to be a safe and useful drug in effectively treating dyslipoproteinaemia in CAPD patients. PMID- 8352700 TI - Decreased uptake of L-cystine by duodenal brush border membrane vesicles from patients with cystinuria. AB - BACKGROUND: The pathophysiology of cystinuria remains unclear. Decreased absorption of L-cystine across brush border membranes of small intestinal and renal proximal tubular epithelial cells is likely but has not been directly demonstrated. AIMS: To compare the rates of L-cystine transport by isolated duodenal brush border membranes of normal individuals and patients with cystinuria. METHODS: Distal duodenal biopsies were taken from normal individuals and patients with cystinuria. Brush border membrane vesicles (BBMV) were prepared using magnesium aggregation and differential centrifugation and the rates of L cystine transport into the vesicles measured using a rapid filtration technique. RESULTS: Rates of L-cystine transport by BBMV from patients with cystinuria were reduced at 5 minute (p = 0.003) and 30 minute (p = 0.053). Time points, indicating that L-cystine absorption across brush border membranes is abnormal in cystinuria. PMID- 8352701 TI - Aconitine poisoning following the ingestion of Chinese herbal medicines: a report of eight cases. AB - BACKGROUND: Traditional Chinese medicines often contain 'chuanwu' and 'caowu', the roots of certain Aconitum species which are thought to have an anti inflammatory effect in many conditions. Excessive amounts of these materials, which contain diterpene alkaloids particularly aconitine, can produce toxic effects and occasional fatalities. AIMS: This study was conducted to document the adverse effects related to these herbal medicines which resulted in hospital admission and to determine the outcome in these patients. METHODS: A retrospective survey was conducted of patients admitted to the Prince of Wales Hospital, Hong Kong with suspected adverse effects from Chinese herbal medicines containing chuanwu or caowu over a two year period from 1989 to 1991. RESULTS: Eight patients were identified with features of mild to moderate intoxication including nausea and vomiting, paraesthesiae or numbness in the mouth and extremities, hypotension and ventricular extrasystoles. The management of aconitine poisoning is essentially supportive and in-hospital observation with ECG monitoring should be continued for at least 24 hours because of the risk of cardiovascular collapse and ventricular arrhythmias. The medical profession and general public should be alerted to the potential toxicity of these herbs and their usage should be controlled by legislation in Hong Kong as it is in some other countries. PMID- 8352702 TI - Yttrium synovectomy: a meta-analysis of the literature. AB - BACKGROUND: Yttrium synovectomy for chronic synovitis of the knee enjoys widespread usage in Australia with approximately 400 patients receiving yttrium 90 in 1991. Despite abundant anecdotal evidence of its efficacy there is a paucity of controlled trials and those that have been done have produced conflicting results and have been of insufficient sample size. AIMS: To critically and quantitatively evaluate the published English literature on comparative trials of yttrium-90 therapy for chronic synovitis of the knee. METHODS: The technique of meta-analysis was utilised. The literature search was carried out using the MeSH terms of synovectomy and knee; and yttrium. This was augmented by referring to reviews, current textbooks and back-references. Outcome measures varied between trials but could be grouped as treatment success. The Peto modification of Mantel and Haenszl was used for statistical pooling of data yielding a pooled odds ratio (OR). RESULTS: The literature search revealed ten controlled trials of which two were excluded from further analysis. Yttrium was superior to placebo (OR 2.42, 95% CI 1.02-5.73) but this result should be interpreted with caution due to possible publication bias. Yttrium was not superior to triamcinolone (OR 1.89, 95% CI 0.81-10.55) or other active modalities (OR 1.04, 95% CI 0.72-1.52). Further research comparing yttrium with other modalities is necessary to properly determine its place in rheumatological practice. PMID- 8352703 TI - Duplicate reporting of AIDS cases between two neighbouring countries. AB - AIMS: To measure the extent and characteristics of cases of duplicate notification of diagnoses of Acquired Immunodeficiency Syndrome (AIDS) between Australia and New Zealand. METHODS: Cases of AIDS notified to the national AIDS registries in both Australia and New Zealand were identified, using date of birth and a name code. Cases determined to have been notified to both registries were analysed with respect to exposure category, country of birth and country of death. RESULTS: Twenty-six cases of AIDS were determined to be common to both registries, representing 1.1% of cases notified to the Australian registry and 11.1% of cases notified to the New Zealand registry. Exposure to HIV was attributed to male homosexual contact for all cases, and a history of injecting drug use was reported more frequently to the Australian registry for the cases in common. For the majority of cases notified to both registries, country of birth was recorded as New Zealand. Deaths following AIDS were reported as occurring in both countries with equal frequency. PMID- 8352704 TI - Repair of the anterior mitral leaflet. AB - BACKGROUND: Repair rather than replacement of the diseased mitral valve has been the goal of the cardiac surgeon. Although well accepted for posterior leaflet pathology, a diseased anterior leaflet was believed by some to be irreparable. AIMS: To assess the result of reconstructive mitral valve surgery involving the anterior mitral leaflet in a selected group of patients. METHODS: Twenty consecutive patients with degenerative (19), ischaemic (one) and congenital/calcific mitral regurgitation were evaluated. There were five females and 15 males with a mean age of 62 +/- 12 years (41-75 years). The technique used to repair these valves included chordal transposition, leaflet plication commissuroplasty and a new technique we call leaflet repositioning. RESULT: There were no deaths, follow-up is complete with mean follow-up of 31 +/- five months (two-102) months. All patients have had 2DE and 13 TOE as well. There have been no reoperations due to failure of the repair, 95% of patients are in NYHA Class I II post operative, while 15% have significant residual regurgitation. PMID- 8352705 TI - Pneumococcal vaccine: current status. PMID- 8352706 TI - Clinical implications of laboratory testing for the thrombophilic disorders. PMID- 8352707 TI - Alcohol and the J-curve survival. PMID- 8352708 TI - Prolonged exacerbation of the neurological sequelae of stroke by post-stroke partial epileptic seizures. PMID- 8352709 TI - Stem cell mobilisation with cyclophosphamide--what dose? PMID- 8352710 TI - Fatal transfusion-associated graft-vs-host disease. PMID- 8352711 TI - Anabolic steroid hepatotoxicity: lessons to be learnt? PMID- 8352712 TI - Spontaneous involution of an atrial myxoma complicated by bacterial endocarditis. PMID- 8352713 TI - Delays preceding admission to hospital and treatment with thrombolytic agents of patients with possible heart attack. PMID- 8352714 TI - Radiofrequency catheter ablation for paroxysmal supraventricular tachycardia: a report of 135 procedures. AB - BACKGROUND: Paroxysmal Supraventricular Tachycardia (PSVT) is a common condition which until recently has been treated with anti-arrhythmic drugs or surgery. Radiofrequency (RF) catheter ablation is a new mode of treatment which provides a cure of this condition. AIMS: To present our early experience of RF catheter ablation for PSVT. METHODS: One hundred and thirty-five procedures were performed in 117 patients. The diagnostic study and therapeutic catheter ablation were performed as a combined electrophysiological procedure in 74 patients (63%). In 58 patients (50%), PSVT was due to Atrio-ventricular junctional (nodal) re entrant tachycardia (AVJRT). Twenty-five of the 58 patients underwent a fast pathway ablation while 33 had ablation of their slow pathway. The mean number of radiofrequency pulses delivered was ten for a mean duration of 25 seconds. Radiofrequency ablation of accessory pathways was attempted in 58 patients; pathways were left-sided in 29 patients, postero-septal in 21, midseptal in five, Mahaim connection in two, antero-septal in one and right free wall in one patient. One patient with incessant automatic atrial tachycardia also underwent a successful RF ablation. RESULTS: Using RF ablation cure of PSVT was achieved in 90% of patients. Cure of AVJRT was achieved in 95% (55/58) of patients using either fast or slow pathway ablation. Only one patient required permanent pacemaker implantation for Mobitz type I AV block following fast pathway ablation. The overall success rate for ablation of accessory pathways was 85%. There is an operator learning curve for this procedure suggested by the fact that the success rate for accessory pathway ablation at first attempt was 63% in the first 29 patients and 93% in the remaining 29. There was no significant morbidity or mortality during or after the procedure. In a mean follow-up of nine months in the patients with successful ablation only two patients with AVJRT had a recurrence of documented PSVT. Both these patients had successful repeat RF ablation. Catheter ablation using radiofrequency energy is an effective and safe therapeutic option for patients with symptomatic PSVT. PMID- 8352715 TI - Australian Geriatrics Society. Annual scientific meeting. Sydney, 29 April - 1 May, 1993. Abstracts. PMID- 8352716 TI - Evolutionary adaptation and stress: energy budgets and habitats preferred. AB - Natural populations are normally exposed to substantial environmental stress. The consequences of stress include elevated metabolic costs and additive genetic variability. From the former, preferred habitats should be located in environments corresponding to minimum total energy expenditure. This tendency occurs in the field for behavioral adaptation of Drosophila to variable temperature (and humidity) conditions. Laboratory studies of resource preference in Drosophila suggest a low genetic variability. However, under more stressful field conditions, genetic variability should be higher. Habitat preference studies under stressful conditions therefore need to be emphasized in modeling situations in nature. PMID- 8352717 TI - Selection for high and low pupation height in Drosophila ananassae. AB - Selection for high and low pupation height in Drosophila ananassae was carried out for 10 generations. Response to selection resulted in rapid divergence in pupation height in replicates of both high and low lines. There was a significant difference in mean pupation height among high, low, and control lines. Regression coefficients for both high and low lines were significantly different from zero. The realized heritability over 10 generations was 45-49 for the high lines and 26 29 for the low lines. The F1 hybrids produced by making reciprocal crosses between high and low lines showed intermediate pupation height. These findings suggest that pupation height in D. ananassae is under polygenic control, with a substantial amount of additive genetic variation. PMID- 8352718 TI - Comparisons of subcolonies of selectively bred long-sleep and short-sleep mice. AB - The Albany subcolony of the selectively bred Long- and Short-Sleep mice was directly compared to the original Colorado colony. As expected from the additional selection applied to the Colorado colony, small differences in the selection phenotype, loss of the righting reflex duration following ethanol treatment, were observed in the Short-Sleep line. However, no colony differences existed in three other indices of ethanol effects. Clear line differences in the shape of the locomotor activity dose-response curve, thermoregulatory effects of ethanol, and ethanol elimination rate replicated earlier findings, but these differences were similar in the two colonies. These data argue for stability of the polygenic control system and provide a picture of remarkable similarity of the two sublines, which were separated by more than 30 generations. PMID- 8352719 TI - Olfactory discrimination of urinary odortypes from congenic strains (DBA/1Bg and DBA1.C57BL10-YBg) of mice differing in their Y chromosomes. AB - Differential effects of one or more genes in the nonpseudoautosomal region of the DBA1 and C57BL10 Y chromosomes on offensive attack may be mediated, at least in part, by differential effects of this Y chromosomal gene(s) on the sending and receiving of discriminable urinary odortypes. This hypothesis is based, in part, on the report that urine from a pair of Y chromosomal congenic strains (C57BL6.AKR-Y and C57BL6) of mice can be discriminated in a Y maze test. The AKR and C57BL6 Y chromosomes come from two distinct species of mouse (Mus domesticus and Mus musculus, respectively). Thus, this Y chromosomal variant exists between mouse species. The DBA1 and C57BL10 Y chromosomes come from a single species, Mus musculus. Here we show that in the Y maze system previously used, urine from mice with the DBA1 and with the C57BL10 Y chromosomes can also be discriminated. Thus, there are discriminable urinary odortypes for this pair of Y chromosomes from the same species, Mus musculus. PMID- 8352720 TI - A comparison of the contribution of the major histocompatibility complex (MHC) and Y chromosomes to the discriminability of individual urine odors of mice by Long-Evans rats. AB - A go/no-go operant task was used to assess the ability of male Long-Evans rats to discriminate between the urine odors from pairs of intact MHC congenic mice (C57BL/6-H-2Kb/J and C57BL/6-H-2Kbm1/ByJ), intact Y congenic mice (DBA1 and DBA1.C57BL10-Y), and castrated Y congenic mice of these two strains. The MHC congenic strains differ in alleles of the H-2 K locus, while the Y congenic strains differ in the nonrecombining part of the Y chromosome. Analysis of the number of correct responses to a criterion of 85% correct on each block of 20 trials revealed that the ability of the subjects to discriminate between urine odors did not differ whether samples were from pairs of intact MHC congenic mice, intact Y congenic mice, or castrated Y congenic mice. These findings are consistent with the hypothesis that individually unique urine odors may be influenced both by genes in the nonrecombining part of the Y chromosome and by genes in the major histocompatibility complex of chromosome 17. These odors are not androgen dependent. Such urinary chemical signals may be involved in pregnancy block (the Bruce effect), aggression, and other mouse social behaviors. PMID- 8352721 TI - Neonatal vestibular stimulation and mating in cerebellar mutants. AB - Two cerebellar mutants, staggerer and reeler, and their congenic nonmutants were used in this experiment. Experimental animals were subjected to intense rotational stimulation on a tilted plane during the first 3 weeks of life, while controls were left nonstimulated. The capacity for mating, as evidenced by vaginal plugs or the occurrence of pregnancy, was assayed during two periods: between 36 and 89 days of age (Experiment A) and between 90 and 120 days of age (Experiment B). During Experiment A the mutants as well as the normals were caged inter se with partners of the opposite sex. During Experiment B the animals were caged with intact, sexually experienced partners. The animals were examined daily for evidence of mating. During Experiment A, only 3 of the 89 couples participating in this study showed evidence of mating. During Experiment B, the number of males of both strains which had mated increased significantly. The staggerer females showed a relatively high level of mating activity, whether stimulated or not. The reeler females, in contrast, rarely mated, although early stimulation significantly increased the level of sexual efficiency. The majority of the normal males and females mated, whether stimulated or not. It was concluded that massive motor-sensory stimulation in infancy, improving gait and body balance in staggerer and reeler mice, may also improve mating efficiency. PMID- 8352722 TI - Estimating and controlling for the effects of volunteer bias with pairs of relatives. AB - If pairs of relatives correlate in their liability to participate in a research project, it is possible to test for the effects of volunteering on the criterion variable of interest. Much of the information for this test comes from a difference in criterion variable mean between individuals with and those without a cooperative relative. Also, if data are available from more than one class of relative, it may be possible to discriminate between (i) volunteering that occurs as a consequence of the criterion variable and (ii) volunteering as a cause of the criterion. Likelihood formulae are presented that permit quantification and significance testing of volunteer bias. If data are collected from a genetically informative design such as a twin study, it is possible to estimate genetic and environmental parameters independent of the contaminating effects of such bias. We describe some methods of reducing the computational burden of multidimensional integration to allow extension to multivariate data. Implications for research design and management are discussed. PMID- 8352723 TI - Familial transmission of cognitive abilities in offspring tested in adolescence and adulthood: a longitudinal study. AB - As part of a follow-up study of now-adult offspring who originally participated in the Hawaii Family Study of Cognition (HFSC) from 1972 to 1976, 49 females and 46 males from 73 families of Caucasian ancestry and 63 females and 55 males from 92 families of Japanese ancestry were retested (average test-retest interval, 13 years) on the battery of cognitive abilities tests they took as adolescents. Age corrected scale scores for verbal ability, spatial ability, perceptual speed, visual memory, and unrotated first principal component were calculated for the offspring's fathers and mothers, for their original HFSC testing, and for the retesting. Model-fitting procedures for a univariate model of familial transmission indicated significant differences in the parameters between the two racial/ethnic groups for all five cognitive abilities scales. These procedures also demonstrated no significant differences in familialities for offspring abilities in adolescence vs. mature adulthood across all five abilities scales and both racial/ethnic groups. PMID- 8352724 TI - Nature, nurture, and conservatism in the Australian Twin Study. AB - Church attendance, educational level, and six conservatism scales were the subject of a multivariate behavior-genetic analysis by Truett et al. (Behav. Genet. 22, 43-62, 1992), based on responses from a large sample of adult Australian twins. These data are here analyzed in a different way to elicit general conservatism factors in the genetic, shared environmental, and unshared environmental covariation. The general genetic factor appears mainly to reflect intellectual sophistication; the general environmental factors, religious affiliation. These factors are similar, although not identical, for men and women. PMID- 8352725 TI - Segregation analysis of speech and language disorders. AB - Complex segregation analysis was performed on pedigrees ascertained through 45 probands (26 males, 19 females) with a history of preschool speech and language disorders. Hypotheses concerning mode of inheritance were tested using the POINTER segregation analysis program. Although there is strong evidence for familial transmission of this trait, we were unable to distinguish between a major gene and multifactorial transmission model using likelihood-ratio chi square tests. Future studies with quantitative measures of speech and language disorders are needed to resolve the issue of mode of inheritance for this trait. PMID- 8352726 TI - Radical-induced chain oxidation of proteins and its inhibition by chain-breaking antioxidants. AB - Exposure of proteins to oxygen-centred radicals results in dramatic changes in their structure, stability and function; properties that have been studied in many laboratories from a qualitative viewpoint. To allow a quantitative evaluation, we subjected aerated solutions of BSA to hydroxyl and superoxide anion radicals generated radiolytically under conditions where all radicals formed reacted with the protein (as judged by maximum damage to BSA). We observed that for each radical generated approx. 15 amino acids were consumed initially. Similar results were found with lysozyme and melittin. Such a massive consumption of BSA's amino acids was not observed when irradiations were carried out under anaerobic conditions. When bilirubin or Trolox (a water-soluble analogue of vitamin E) was added at a 2-fold molar excess over BSA, initial consumption of all measured amino acids, except tryptophan, decreased 4-fold. The total mass of amino acids initially protected (from consumption) exceeded the mass of antioxidants consumed by more than a factor of 20. Such protection of amino acids was not observed when the antioxidant-inactive acetyl Trolox was used. These results suggest that radical-mediated oxidation of proteins can proceed via a previously unrecognized chain reaction that may be inhibited by chain-breaking antioxidants. PMID- 8352727 TI - Interactions between active-site-serine beta-lactamases and compounds bearing a methoxy side chain on the alpha-face of the beta-lactam ring: kinetic and molecular modelling studies. AB - The interactions between three class A beta-lactamases and compounds bearing a methoxy side chain on the alpha-face of the beta-lactam ring (cefoxitin, moxalactam and temocillin) have been studied. When compared with the situation prevailing with good substrates, both acylation and deacylation steps appeared to be severely impaired. Molecular modelling studies of the structures of the Henri Michaelis complexes and of the acyl-enzymes indicate a major displacement of the crystallographically observed water molecule which connects the glutamate-166 and serine-70 side chains and underline the role of this water molecule in both reaction steps. PMID- 8352728 TI - Biotin binders selected from a random peptide library expressed on phage. AB - Recombinant biotin-binding phages were affinity-selected from a random peptide library expressed on the surface of filamentous phage. Phage binding to biotinylated proteins was half-maximally inhibited by micromolar concentrations of a monobiotinylated molecule. Sequencing of the peptide inserts of selected phages led to the identification of a previously unknown biotin-binding motif, CXWXPPF(K or R)XXC. A synthetic peptide containing this sequence motif inhibited streptavidin binding to biotinylated BSA with an IC50 of 50 microM. This compound represents the shortest non-avidin biotin-binding peptide identified to date. Our results illustrate that phage display technology can be used to identify novel ligands for a small non-proteinaceous molecule. PMID- 8352729 TI - DNA substrate specificity of pea DNA methylase. AB - DNA methylase, present in low-salt extracts of nuclei prepared from Pisum sativum shoot tips, methylates model DNA substrates containing CNG trinucleotides or CI dinucleotides only. The binding to the hemimethylated trinucleotide substrates is very much stronger and more persistent than the binding to the unmethylated substrates or to the hemimethylated dinucleotide substrate. When the DNA concentration is limiting, the rate of methyl-group transfer with the hemimethylated CNG substrate is much greater than that with the unmethylated CNG. However, the Vmax. is similar for the two CNG substrates. On fractionation using Q-Sepharose, two peaks of activity are seen with different relative activities using the di- and trinucleotide substrates. The relative activity with these substrates changes during purification, during plant growth and on heating at 35 degrees C as well, indicating that more than one enzyme or more than one form of the enzyme may be present. PMID- 8352730 TI - The role of the 5'-flanking region in the cell-specific transcription of the human von Willebrand factor gene. AB - Transcriptional regulation of the human von Willebrand factor (vWF) gene was investigated in calf pulmonary artery endothelial (CPAE), HeLa, COS 7 and Hep G2 cells. Various lengths of flanking sequences extending up to 2123 bp 5' of the transcription initiation site and containing 19 bp of the first exon, were linked to the bacterial chloramphenicol acetyltransferase (CAT) gene and these constructs were assayed in transient transfection assays. Sequences up to 89 bp upstream of the cap site showed transcriptional activity in all cell types. Sequences between -147 and -419 bp markedly reduced CAT activity in CPAE cells and abolished it in other cell lines. A domain from -592 to -810 bp generated low levels of expression only in CPAE cells. This transcriptional activity was repressed with constructs containing 1041 to 1240 bp upstream of the cap site. Endothelial cell-specific transcription was restored by a construct that contained 1286 bp upstream of the cap site. The additional 46 bp upstream of the negative regulatory domain were within the 5' end of an inverse human Alu-family DNA repeat. RNAase-protection assays confirmed the correct transcriptional initiation. The sequence between -89 and -420 contained at least one negative regulatory element able to repress the CAT gene expression controlled by the heterologous thymidine kinase promoter in all cell types. A construct that included the sequence from -89 to -1286 bp increased the transcriptional activity directed by the thymidine kinase promoter only in CPAE cells. These results indicate that negative and positive elements in the 5'-flanking region interact to regulate vWF gene expression. PMID- 8352732 TI - A mobile element on a virus particle surface identified by nuclear magnetic resonance spectroscopy. AB - The presence of a mobile element in the coat protein of pepper ringspot tobravirus (PRV) has been established by 1H n.m.r. spectroscopy; two-dimensional correlation spectroscopy (COSY) measurements show that this element consists of alanine, asparagine, glycine, proline, serine and threonine only. By reference to the amino acid sequence of the coat protein, it is concluded that the mobile element is associated with the C-terminal region and consists of between 11 and 38 residues. PMID- 8352731 TI - Correlation between secretion and phospholipase D activation in differentiated HL60 cells. AB - Receptor-directed agonists including N-formylmethionyl-leucyl-phenylalanine (fMetLeuPhe), C5a, ATP and UTP all activate phospholipase D (PLD), which is accompanied by secretion in differentiated HL60 cells. Interference in the production of phosphatidase (PA) by the PLD pathway by diverting it towards the production of phosphatidylethanol (PEt) in the presence of ethanol leads to near total inhibition of the secretion evoked by ATP and UTP and a partial inhibition of that evoked by fMetLeuPhe and C5a. In streptolysin-O-permeabilized cells, fMetLeuPhe is able to activate PLD, and this is dependent on the presence of a low concentration of guanosine 5'-[gamma-thio]-triphosphate (GTP[S]). Ca2+ (10 microM) and GTP[S] individually or in combination are also able to activate PLD and secretion. The stimulation of secretion in permeabilized cells stimulated by Ca2+ alone or fMetLeuPhe or GTP[S] is also abrogated when the production of PA is diverted to PEt by the presence of ethanol. Activation of PLD by GTP[S] or fMetLeuPhe is decreased if the cells are permeabilized first and GTP[S] or fMetLeuPhe is added subsequently. This corresponds well with the loss of the secretory response. We conclude that the ability of GTP[S] or fMetLeuPhe to stimulate secretion from permeabilized cells is dependent on a prior activation of the PLD signalling pathway. PA, generated as a consequence of PLD activation, acts as second messenger that can provide an initiating signal for secretion and is not required for exocytosis itself. PMID- 8352733 TI - Non-enzymic glycation of collagen inhibits binding of oxidized low-density lipoprotein. AB - We have examined the effect of non-enzymic glycation of native soluble collagen, in solution or in gels, on binding of oxidized low-density lipoprotein (LDL). We found the following. (1) Glycation markedly inhibited binding of LDL. This is contrary to results previously reported; the difference may be attributable to the use of detergent- and heat-denatured collagen, covalently bound to agarose beads, in the earlier study. (2) With increased duration of glycation, collagen solution would not gel, and preformed gels dissolved. (3) [14C]Glucose bound to collagen gels dissociated slowly, even at pH 5, suggesting that it was not present as a Schiff's base; in addition, ketoamines, pentosidine and fluorescent advanced glycation products were not detectable in glycated collagen gels, although they accumulated in tendon collagen glycated under the same conditions. It is hypothesized that the difference in glycation effects between gel and tendon may be due to the strength of cross-linking before glycation: the increase in intermolecular distance in collagen fibrils which results from glycation disrupts the fibrils in gels, preventing binding of LDL and formation of glycation-dependent cross-links, whereas the extensive cross-linking in tendon maintains the intermolecular distances within a range which permits formation of glycation cross-links. PMID- 8352734 TI - Biosynthesis of 3,4-didehydroretinol from retinol by human skin keratinocytes in culture. AB - The uptake and metabolism of radiolabelled retinol was studied in cultivated human skin cells. Normal epidermal keratinocytes in primary culture were able to incorporate unbound [11,12-3H]all-trans-retinol from the growth medium and transform it into 3,4-didehydroretinol (dehydroretinol) in a dose- and time dependent manner. A total of 23% of the radioactive label became cell-associated during a 48-h incubation period when added at 7 nM to differentiated keratinocytes submerged in serum-containing, high-calcium (1.56 mM) culture medium. At that time point, 25-30% of cell-bound radioactive retinol had been converted into dehydroretinol, with no labelled retinal, dehydroretinal, retinoic acid or dehydroretinoic acid being detected in cells or medium. Thus dehydroretinol, which occurs physiologically in mammalian skin tissue in vivo, was identified as the predominant neutral retinol metabolite in cultured keratinocytes using h.p.l.c. and anhydro-derivatization procedures. At least 94% of the product, along with its precursor, was present in the cells in esterified form, with no traces of the compound being secreted into the cell environment. The rate of formation of dehydroretinol from its precursor was significantly lower in keratinocytes grown in serum-free, low-calcium (0.09 mM) culture medium, and in medium pre-incubated with excess unlabelled substrate. Furthermore, the application of 13-cis-retinoic acid (isotretinoin), a therapeutic retinoid drug known to markedly reduce dehydroretinol levels in human skin, blocked the biosynthesis of this metabolite in cultured keratinocytes. The 3,4 dehydrogenation pathway observed in this study could not be shown to operate to any significant extent in cultures of human epidermal melanocytes or dermal fibroblasts, supporting the hypothesis that keratinocytes represent the principal cell type involved in dehydroretinol formation from retinol in human skin. PMID- 8352735 TI - A glycosulphatase that removes sulphate from mucus glycoprotein. AB - A novel glycosulphatase has been purified from a mucus glycopeptide-degrading Prevotella from the colon. The purified enzyme removed inorganic [35S]sulphate from 35S-labelled native rat gastric mucus glycoprotein. Desulphation of mucus glycoprotein was initially rapid (19% complete after 10 min) but then plateaued, reaching only 33% after 3 h. Crude periplasmic extracts could remove 79% of the radioactivity as inorganic sulphate. These results suggest that steric hindrance may limit the access of the purified glycosulphatase to the mucus glycoprotein oligosaccharide chains in the absence of glycosidases, and/or that the enzyme may have the wrong specificity for some of the remaining sulphated sugars in the chains. The apparent molecular mass of the enzyme was 111 kDa as judged from gel exclusion chromatography, and it appeared to be composed of two identical subunits. The enzyme was localized in the periplasm of the bacterium, and using pig gastric mucus glycopeptide as a growth substrate markedly increased enzyme levels. Enzymic activity increased at the end of the growth phase. The substrate specificity of the enzyme was tested against low-molecular-mass sulphated molecules. The monosaccharides glucose 6-sulphate and N-acetylglucosamine 6 sulphate were rapidly desulphated, the latter being the major sulphated sugar in some mucus glycoproteins. Lactose 6-sulphate, galactose 6-sulphate, sulphated steroids and unsaturated disaccharide sulphate breakdown products from chondroitin sulphate were not desulphated. Glycosulphatases which can remove sulphate from mucus glycoproteins may play an important role in the degradation of highly sulphated mucus glycoproteins in the digestive tract, and could modify the effectiveness of mucus glycoproteins in mucosal protection. PMID- 8352736 TI - Properties of the pyridoxaldimine form of glutamate semialdehyde aminotransferase (glutamate-1-semialdehyde 2,1-aminomutase) and analysis of its role as an intermediate in the formation of aminolaevulinate. AB - Glutamate semialdehyde aminotransferase (glutamate-1-semialdehyde 2,1 aminomutase; EC 5.4.3.8) was converted into its pyridoxaldimine form by exhaustive replacement of endogenous pyridoxamine phosphate with pyridoxal phosphate. The isomerization of glutamate 1-semialdehyde to 5-aminolaevulinate by this form of the enzyme followed an accelerating time course which indicated that the enzyme initially had no activity but was converted into the active pyridoxamine phosphate form in an exponential process characterized by a rate constant (k) of 0.027 s-1. The pyridoxaldimine form of the enzyme was converted rapidly into the pyridoxamine form by (S)-4-aminohex-5-enoate and much more slowly by 4-aminobutyrate. The steady-state velocity of the enzyme increased in a markedly non-linear fashion with increasing enzyme concentration, indicating that the extent of dissociation of an intermediate in the reaction to free diaminovalerate and the pyridoxaldimine form of the enzyme depends upon the concentration of the enzyme. PMID- 8352739 TI - Cloning of the gene for glutamate decarboxylase and its expression during conidiation in Neurospora crassa. AB - Neurospora crassa glutamate decarboxylase (GAD) is produced during conidiation and stored in dormant conidia. Polyclonal antibody was generated to GAD that had been purified to homogeneity. The anti-GAD antibody was specific for N. crassa GAD and inhibited GAD activity. The level of GAD protein decreased during conidial germination, indicating that GAD was degraded during this phase of development. The anti-GAD antibody was used to isolate a cDNA clone of GAD from a lambda ZAP cDNA expression library. Escherichia coli containing a plasmid with the cDNA insert produced GAD activity. The cDNA clone contained a 2.6 kbp insert and hybridized to a 2.6 kb mRNA species from conidiating cultures of N. crassa. GAD mRNA was not present in vegetative hyphae. In conidiating cultures, GAD mRNA was first detected when conidia began to appear. The level of GAD mRNA increased as conidiation progressed. This is the first example of the cloning of an enzyme that is regulated at the level of mRNA during the asexual developmental cycle of N. crassa. PMID- 8352737 TI - Purification and properties of the uroporphyrinogen decarboxylase from Rhodobacter sphaeroides. AB - Uroporphyrinogen decarboxylase (EC 4.1.1.37) was purified 600-fold from Rhodobacter sphaeroides grown anaerobically in the light. The enzyme, under both denaturing and non-denaturing conditions, is a monomer of M(r) 41,000. The Km values are 1.8 microM and 6.0 microM for the conversion of uroporphyrinogen I and III to coproporphyrinogen I and III respectively. The enzyme is susceptible to inhibition by both uroporphyrinogen and uroporphyrin. The pH optimum is 6.8 and the isoelectric point is 4.4. The importance of cysteine and arginine residues is implicated from studies with inhibitors. The sequence of the first 29 amino acids of the N-terminus shows a high degree of similarity to the primary structures of other uroporphyrinogen decarboxylases. Studies on the order of decarboxylation of the four acetic acid side chains of uroporphyrinogen III suggest that at high substrate levels a random route is preferred. PMID- 8352738 TI - Plasma activities of lecithin:cholesterol acyltransferase, lipid transfer proteins and post-heparin lipases in inbred strains of rabbits hypo- or hyper responsive to dietary cholesterol. AB - Plasma lipoproteins, plasma activities of lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP) and post-heparin lipases were measured before and after cholesterol challenge in two inbred strains of rabbits with either a high (hyper-responders) or a low (hyporesponders) response of plasma cholesterol to dietary cholesterol. The purpose of this study was to provide clues about the mechanisms underlying the effect of dietary cholesterol on lipoprotein levels and composition, and particularly those underlying the strain difference of this effect. Cholesterol feeding (0.15 g of cholesterol/100 g of diet) caused increased plasma total cholesterol concentrations and an increased ratio of cholesteryl esters:triacylglycerol in all lipoprotein particles in both strains; these effects were significantly greater in hyper- than hypo-responsive rabbits. Feeding on the high-cholesterol diet lowered plasma triacylglycerols in hyper responders, but caused increased plasma triacylglycerol levels in hyporesponders. This was accompanied by significantly greater increases in the activities of hepatic triacylglycerol lipase and lipoprotein lipase in hyper- than in hypo responders. Both strains showed a dietary-cholesterol-induced rise in plasma CETP as well as in PLTP activity. The increase in PLTP activity was greater in the hyper-responders, but that of CETP was less. There was no effect of dietary cholesterol on LCAT activity. It is hypothesized that the lipases are involved in the removal of cholesterol-rich lipoproteins. PMID- 8352740 TI - Phorbol myristate acetate stimulates [3H]choline incorporation into phosphatidylcholine independently of the 'de novo' pathway in Krebs-II ascitic cells: a unique effect of phorbol ester on choline uptake. AB - The effect of phorbol 12-myristate 13-acetate (PMA) on [3H]choline incorporation into phosphatidylcholine (PtdCho) and on the 'de novo' pathway of PtdCho synthesis has been investigated, compared with that of oleic acid, in ascitic strain Krebs-II cells. Both compounds stimulated [3H]choline incorporation into PtdCho, but the PMA-induced incorporation was saturable at concentrations of the agonist around 100 nM, whereas no saturation was noticed with oleic acid up to 1 mM. Chase experiments showed no effect of PMA on the conversion of phosphocholine into CDP-choline. The phorbol ester did not stimulate any of the enzyme activities of the 'de novo' pathway, whereas oleic acid increased specifically by 2.5-fold the CTP:phosphocholine cytidylyltransferase (CT, EC 2.7.7.15) activity. In addition, no change in the subcellular distribution of CT was observed upon incubation with PMA, in contrast with oleic acid treatment. Cells challenged with oleic acid showed a 25-fold increase in diradylglycerol (DG) content, which was not modified upon incubation with 200 nM PMA, the most effective concentration of phorbol ester promoting choline incorporation. Subcellular fractionation of Krebs II cells on Percoll gradients revealed that [3H]PMA and 1-radyl-2-[3H]oleoyl glycerol, derived from exogenously supplied [3H]oleic acid, both exhibited the same enrichment in the endoplasmic reticulum. We have previously shown that the labelled fatty acid also accumulated in the endoplasmic reticulum [Terce, Record, Tronchere, Ribbes and Chap (1992) Biochem. J. 282, 333-338]. However, PMA induced a stimulation of choline uptake, which was not provoked by PMA 4-O-methyl ether, which interacts poorly with protein kinase C. Our data provide evidence that the enhancement of [3H]choline incorporation into PtdCho triggered by PMA and oleic acid proceeds via completely distinct mechanism(s). PMID- 8352741 TI - Hepatic lipase function and the accumulation of beta-very-low-density lipoproteins in the plasma of cholesterol-fed rabbits. AB - The accumulation of cholesterol-rich beta-very-low-density lipoproteins (beta VLDL) in the plasma of rabbits fed on a high-fat high-cholesterol diet is due to a defect in the clearance of these lipoprotein remnants from circulation by the liver. In view of the evidence that hepatic lipase participates in the process of rapid removal of remnants from circulation, and considering that rabbits are naturally deficient in hepatic lipase, we examined whether this defect in the clearance of beta-VLDL could be reversed by exogenous hepatic lipase. We report that treatment in vitro of [3H]cholesterol-labelled beta-VLDL, or rat chylomicrons, with hepatic lipase resulted in the formation of particles that were rapidly cleared from circulation by the liver when injected intravenously into hypercholesterolaemic rabbits. These results are consistent with the notion that, in addition to the well-established requirement for lipoprotein lipase activity, the generation of remnants capable of being efficiently taken up by the liver also requires the action of hepatic lipase. Lipoprotein lipase acts on triacylglycerol-rich lipoproteins to transform them into particles (remnants) which bind to the surface of liver cells, where they become accessible to hepatic lipase. Hepatocyte endocytosis of these remnants occurs only after further modification by hepatic lipase. According to this scheme, the results presented suggest that the accumulation of beta-VLDL in the circulation of rabbits fed on a high-fat high-cholesterol diet is the result of the saturation of the available hepatic lipase by abnormally high levels of lipoprotein-lipase-generated chylomicron remnants. PMID- 8352742 TI - Processing of chimeric mammalian cytochrome b5 precursors in Escherichia coli: reaction specificity of signal peptidase and identification of an aminopeptidase in post-translocational processing. AB - A chimeric precursor interlinked by an arginine residue between the full-length signal sequence of alkaline phosphatase and the eukaryotic cytoplasmic cytochrome b5 was constructed. Expression of the chimeric precursor protein in Escherichia coli resulted in efficient export of spectrally authentic cytochrome b5 into the periplasm [Karim, Harding, Evans, Kaderbhai and Kaderbhai (1993) Bio/Technology 11, 612-618]. On sequencing, the apparent absence of arginine at the N-terminus of the secreted cytochrome b5 implied that the chimera was either miscleaved by signal peptidase or further processed following signal excision by an uncharacterized peptidase. The influence of the N-terminal region of cytochrome b5 on the unusual processing of the chimeric precursor was investigated by engineering a number of variant forms in which the region between Arg+1 and the mature portion of cytochrome b5 was extended and varied. Observations of the in vivo processed patterns of these variant cytochrome b5 forms exported into the periplasm revealed that the absence of arginine was due to neither miscleavage of the translocated precursor by the signal peptidase nor the nature of the early region of cytochrome b5. In fact, the selective excision of the arginine residue occurred subsequent to signal sequence deletion by an aminopeptidase which was sensitive to the metal chelator o-phenanthroline. We show that this aminopeptidase also participates in the trimming of the N-terminal arginine residue of the bacterial alkaline phosphatase to generate the three isoenzymes in the periplasm. PMID- 8352743 TI - Adenosine 5'-[alpha beta-methylene]triphosphate potentiates the oscillatory cytosolic Ca2+ responses of hepatocytes to ATP, but not to ADP. AB - Single rat hepatocytes microinjected with aequorin generate oscillations in cytosolic free Ca2+ concentration ([Ca2+]i) when stimulated with agonists acting through the phosphoinositide signalling pathway. The duration of these transients has been shown to be characteristic of the stimulating agonist, so that transients of very different duration can be induced in the same individual hepatocyte by different agonists. In a previous study we have shown that ADP and ATP, which are believed to act through a single P2y-purinoceptor species, elicit very different [Ca2+]i responses in most of the hepatocytes. We have interpreted this as evidence for two Ca(2+)-mobilizing purinoceptors. The methylated derivative of ATP, adenosine 5'-[alpha beta-methylene]-triphosphate (pp[CH2]pA), is only a weak P2y-purinoceptor agonist. When 100 microM pp[CH2]pA was supplied to aequorin-injected hepatocytes, there was no effect on [Ca2+]i. However, 25 microM pp[CH2]pA co-supplied with ATP causes a potentiation of the [Ca2+]i response in most of the hepatocytes. The effect was specific for ATP-induced transients; [Ca2+]i transients induced by other agonists, and importantly by ADP, were not affected by addition of pp[CH2]pA. This further illustrates differences in the actions of ADP and ATP, strengthening the argument for separate receptors for these nucleotides. PMID- 8352744 TI - Nuclear import of the human androgen receptor. AB - Nuclear import of the human androgen receptor was investigated by immunocytochemical analysis of androgen receptor deletion and substitution mutants, which were transiently expressed in COS-1 cells. The signal responsible for nuclear import is encoded by amino-acid residues 608-625 and is functionally similar to the bipartite nucleoplasmin nuclear-localization signal. Although the subcellular distribution of androgen receptors mutated in the DNA-binding domain was unchanged compared with the wild-type androgen receptor, in the presence of ligand these mutations resulted in part of the receptor population forming clusters. Depending on the presence or absence of the bipartite nuclear localization signal, clusters were formed in the nucleus or in the cytoplasm, respectively. Expression of the wild-type androgen receptor in different cell lines revealed a cell-line-specific subcellular distribution of the unliganded receptor. The androgen receptor was predominantly nuclear when expressed in HeLa cells, whereas mainly cytoplasmic staining was observed when it was expressed in COS-1 cells. In the presence of hormone, the androgen receptor was located in the nucleus, independent of the cell line that was expressing the receptor. Anti androgens and various steroid hormones induced the nuclear localization of the wild-type androgen receptor in a dose-dependent way, without activating transcription of an androgen-regulated reporter gene. This indicates that the inability of the tested compounds to activate transcription is not due to inhibited nuclear import. PMID- 8352745 TI - Reduced sulphydryl groups are required for DNA binding of Ku protein. AB - The Ku protein, a DNA-binding complex that is composed of two subunits of 70 kDa and of 86 kDa, has been suggested to play a role in gene transcription. The dependence of the in vitro DNA-binding activity of affinity-purified Ku protein on reduced cysteine residues has been studied using sulphydryl-modifying agents. Inhibition of the DNA-binding activity was caused by alkylation with N ethylmaleimide and by crosslinking with azadicarboxylic acid bis(dimethylamide). Treatment of the protein with a large excess of N-ethylmaleimide after it had bound to DNA did not completely dissociate the complex from the DNA, suggesting that some cysteines may be in direct contact with DNA. Pre-incubation of the protein at 37 degrees C or above caused rapid inactivation of DNA binding. The elevated temperature azadicarboxylic acid bis(dimethylamide) treatments resulted in the formation of a crosslinked product, which was detected by Western blotting. The effects of azadicarboxylic acid bis(dimethylmaleimide) and heat were completely reversible by treatment with a reducing agent, such as dithiothreitol. These results demonstrate that in vitro DNA-binding activity of the Ku protein requires reduced sulphydryl groups. Interestingly, the DNA-binding activity of Ku protein was protected from heat inactivation by the presence of a HeLa cell nuclear extract, suggesting that a nuclear factor or factors may be responsible for the maintenance of the reduced cysteines of the Ku protein in vivo. Thus, the biochemical function of the Ku protein may be regulated through oxidation-reduction of its cysteine residues. PMID- 8352746 TI - DNA precursors are channelled to nuclear matrix DNA replication sites. AB - Studies of replicative DNA synthesis using DNA precursors have shown that the DNA that was replicated most recently is that associated with the nuclear matrix. Consequently, precursors arising via the salvage and the de novo metabolic pathways are first incorporated into a small percentage of the total nuclear DNA that is termed nuclear matrix-associated DNA. These results have been substantiated in cell culture, as well as in intact mammalian systems. Furthermore, when DNA precursors were injected intravenously into regenerating rat liver, a significant lag in the incorporation of orotic acid-derived nucleotides (de novo pathway precursors) into nuclear DNA was observed, when compared with deoxythymidine-derived nucleotides (salvage pathway precursors). This lag in incorporation kinetics was also evident at the nuclear matrix level, although, once incorporated into nuclear matrix-associated DNA, the distribution patterns of both precursors into extra-matrix nuclear DNA fractions were identical. To determine the basis for this kinetic lag, we compared the incorporation kinetics of orotic acid and of deoxythymidine into dTTP and into nuclear matrix-associated DNA, respectively. Orotic acid-derived nucleotides entered the cytosolic dTTP pool before being incorporated into nuclear matrix associated DNA, that is, traversing the classical metabolic route of DNA precursors. Conversely, deoxythymidine-derived nucleotides by-passed the soluble dTTP cellular pool and engaged directly in DNA synthesis at the nuclear matrix. Not only is this the first evidence for nucleotide channelling in an intact mammalian system, but it also forms direct evidence that salvage pathway DNA precursors are channelled to nuclear matrix-associated sites of DNA replication. PMID- 8352748 TI - Developmental changes in the isoelectric variants of rat hepatic hydroxysteroid sulphotransferase. AB - Major isoenzymes of androsterone-sulphating sulphotransferase (AD-ST) were isolated from liver cytosols of weanling and young adult female rats and their isoelectric properties were compared. On chromatofocusing the enzyme activity of young adults was eluted over a wider range of pH than was that of weanling rats. The activity at pH 7.8-7.2 (fraction I) is obvious at both ages, whereas the activity eluted over the pH 6.6-5.5 range (fraction II) is much lower in weanlings than in young adults. The AD-ST activities eluted in fractions I and II were separately purified by 3'-phosphoadenosine 5'-phosphate-agarose affinity chromatography at both ages. Two-dimensional gel electrophoresis of the isolated enzyme revealed several subunits with distinct pI values, but with the same molecular mass, namely 30 kDa. The relative levels of the pI 6.7 and pI 7.2 subunits are high and the relative level of the pI 6.1 is low in fraction I. In fraction II, the levels of pI 6.1 and pI 6.7 subunits are high and the level of the pI 7.2 subunit is low. There is no significant difference in the relative levels of the pI variants in each fraction between weanlings and young adults. The N-terminal amino acid sequences of the pI variants are identical within the area determined, irrespective of animal age or pI values. These results demonstrate that the pI variants of AD-ST are derived from the same precursor by post-translational modification or that they are products of closely related, but distinct, genes. The pI 6.1 and 6.7 subunits presumably increased during the development from the weanling stage to adulthood, resulting in the increase in acidic form(s) of AD-ST (fraction II) in adult females. PMID- 8352747 TI - New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. AB - 301 glycosyl hydrolases and related enzymes corresponding to 39 EC entries of the I.U.B. classification system have been classified into 35 families on the basis of amino-acid-sequence similarities [Henrissat (1991) Biochem. J. 280, 309-316]. Approximately half of the families were found to be monospecific (containing only one EC number), whereas the other half were found to be polyspecific (containing at least two EC numbers). A > 60% increase in sequence data for glycosyl hydrolases (181 additional enzymes or enzyme domains sequences have since become available) allowed us to update the classification not only by the addition of more members to already identified families, but also by the finding of ten new families. On the basis of a comparison of 482 sequences corresponding to 52 EC entries, 45 families, out of which 22 are polyspecific, can now be defined. This classification has been implemented in the SWISS-PROT protein sequence data bank. PMID- 8352749 TI - Phenylalaninylargininylarginine: a novel tripeptide exerting Zn(2+)-dependent, insulin-mimetic inhibitory action on myocardial proteolysis. AB - A novel tripeptide, Phe-Arg-Arg, was found to exert a potent, insulin-mimetic inhibitory action on lysosomal proteolysis in the Langendorff-perfused rat heart. This tripeptide was synthesized based upon its partial structural analogy to the biguanide anti-hyperglycaemic agent, phenformin (phenylethylbiguanide), which has previously been found to exert a Zn(2+)-dependent inhibitory action on lysosomal proteolysis. Hearts were biosynthetically labelled with [3H]leucine in vitro. The percentage change in subsequent release of [3H]leucine (2 mM non-radioactive leucine) was determined in non-recirculating perfusate. The background Zn2+ content of the perfusate was determined to be 20 nM. Major endogenous Zn2+ buffers were present in molar excess of Zn2+: 0.1 mM citrate, 0.2% BSA, and complete physiological amino acids. Infusion of maximally effective levels of chloroquine (30 microM) or insulin (5 nM) caused a 38% inhibition of total proteolysis, which corresponds to the lysosomal subcomponent. In the presence of background levels of perfusate Zn2+ the infusion of Phe-Arg-Arg (10 microM), insulin (5 nM), or phenformin (2 microM) maximally caused a 39% inhibition of [3H]leucine release. Combined infusion of maximally effective levels of insulin and Phe-Arg-Arg, or maximal levels of chloroquine and Phe-Arg-Arg did not cause additive inhibition of [3H]leucine release greater than the 39% inhibition caused by either agent alone, regardless of the order of infusion. Addition of physiological concentrations of Zn2+ (1 microM) to the background perfusate Zn2+ accelerated the insulin-mimetic action of submaximally effective levels of Phe Arg-Arg, and increased its potency. Prior chelation of background Zn2+ by a 3 h perfusion with CaNa2 EDTA (2 microM) reversibly delayed the time course of Phe Arg-Arg action and decreased its potency at submaximal concentrations. PMID- 8352750 TI - L-alanine uptake by rat liver parenchymal and haematopoietic cells during the perinatal period. AB - Alanine disposal by liver parenchymal and haematopoietic cells from 21-day fetuses, newborns and adult rats was studied. Preparations selectively enriched in either haematopoietic cells or hepatocytes were obtained by direct perfusion of fetal- and neonatal-rat livers. L-Alanine transport into liver parenchymal cells was best fitted to two Na(+)-dependent saturable systems. The high-affinity system showed a much higher activity (Vmax.) in hepatocytes from fetuses and newborns than in those from adult rats (2.4, 4.3 and 0.3 nmol/8 min per 10(6) cells for fetuses, newborns and adults respectively). Vmax. for the low-affinity component was slightly lower during the perinatal period than in the adult (about 30 nmol/8 min per 10(6) cells for hepatocytes from fetuses and newborns, versus 48 nmol/8 min per 10(6) cells for adult rat parenchymal cells). Haematopoietic cells from fetal-rat livers showed significant Na(+)-dependent L-alanine uptake which was completely abolished after birth. These results show that the transport systems involved in L-alanine uptake by liver parenchymal cells are fully developed before birth. This probably contributes to fulfilling the high requirement for neutral amino acids for protein synthesis during development. Haematopoietic cells may play an important role in liver amino acid metabolism during fetal life. PMID- 8352751 TI - Kinetics and mechanism of DNA repair: an automated programmable apparatus for fast time-resolved studies of the repair of mammalian DNA after u.v. irradiation. AB - An automated apparatus, designed and constructed for use in fast time-resolved studies of mammalian DNA repair after u.v. irradiation, is described. The methodology makes use of caged DNA-break-trapping reagents, e.g. [alpha 32P]dideoxyadenosine triphosphate [see Meldrum, Shall, Trentham and Wharton (1990) Biochem J. 266, 885-890] and the apparatus incorporates excimer lasers both for the delivery of u.v. damage and for the photoactivation of the caged reagents. The design is based on a sample-changing turntable which permits the sequential irradiation and quenching of samples. A maximum of eight samples can be processed in a single experiment, the sequence of events being programmed on a microcomputer, which permits a very generalized experimental sequence. Pipettes for addition of cells, nucleotides and quenching agent are driven pneumatically. A pair of pneumatically operated platinum electrodes allows electroporation of cells for loading of negatively charged reagents prior to irradiation. The time resolution of the apparatus is dependent upon the experimental scheme used and can be very short (e.g. 1 ms) when caged reagents are used; a more usual period is 1 s for the shortest incubation. PMID- 8352752 TI - N.m.r. and molecular-modelling studies of the solution conformation of heparin. AB - The solution conformations of heparin and de-N-sulphated, re-N-acetylated heparin have been determined by a combination of n.m.r. spectroscopic and molecular modelling techniques. The 1H- and 13C-n.m.r. spectra of these polysaccharides have been assigned. Observed 1H-1H nuclear Overhauser enhancements (n.O.e.s) have been simulated using the program NOEMOL [Forster, Jones and Mulloy (1989) J. Mol. Graph. 7, 196-201] for molecular models derived from conformational-energy calculations; correlation times for the simulations were chosen to fit experimentally determined 13C spin-lattice relaxation times. In order to achieve good agreement between calculated and observed 1H-1H n.O.e.s it was necessary to assume that the reorientational motion of the polysaccharide molecules was not isotropic, but was that of a symmetric top. The resulting model of heparin in solution is similar to that determined in the fibrous state by X-ray-diffraction techniques [Nieduszynski, Gardner and Atkins (1977) Am. Chem. Soc. Symp. Ser. 48, 73-80]. PMID- 8352753 TI - Oxygen Michaelis constants for tyrosinase. AB - The Michaelis constant of tyrosinase for oxygen in the presence of monophenols and o-diphenols, which generate a cyclizable o-quinone, has been studied. This constant depends on the nature of the monophenol and o-diphenol and is always lower in the presence of the former than of the latter. From the mechanism proposed for tyrosinase and from its kinetic analysis [Rodriguez-Lopez, J. N., Tudela, J., Varon, R., Garcia-Carmona, F. and Garcia-Canovas, F. (1992) J. Biol. Chem. 267, 3801-3810] a quantitative ratio has been established between the Michaelis constants for oxygen in the presence of monophenols and their o diphenols. This ratio is used for the determination of the Michaelis constant for oxygen with monophenols when its value cannot be calculated experimentally. PMID- 8352754 TI - Characterization of quail intestinal mucin as a ligand for endogenous quail lectin. AB - The S-type lectins have been shown to be components of mucosal scrapings, and in avian systems these lectins have been localized immunohistochemically to the mucosal surface and goblet cells of the intestine. The interaction of lectin specifically with purified mucin has not, however, been established. Quail intestinal mucin was purified by two subsequent isopycnic density-gradient centrifugations in CsCl and chromatography on Sepharose Cl-2B. Purified mucin, obtained from the void volume of the Sepharose column, was characterized by SDS/PAGE, amino acid and carbohydrate analyses, sensitivity to thiol reduction, and cross-reactivity with antibody preparations to rat and human intestinal mucins on Western blots. Antibody raised against purified quail mucin partially cross-reacts with purified rat, rabbit and human intestinal mucins, and specifically labels the mucosal surface and goblet cells of quail intestine by the immunoperoxidase technique. Protein eluted by lactose from an affinity matrix composed of quail intestinal mucin possessed the same molecular mass on SDS/PAGE as intestinal lectin and reacted on Western blots with a lectin-specific antibody. The data clearly demonstrate the co-localization of lectin and mucin in the quail intestine and also the ability of the lectin to specifically interact with the purified mucin, raising the question of the role of endogenous lectins in secretions. PMID- 8352757 TI - Crystallisation and preliminary crystallographic analysis of recombinant Xenopus laevis Cu,Zn superoxide dismutase b. AB - The recombinant Cu,Zn superoxide dismutase from the South African frog Xenopus laevis, expressed in E. coli, has been crystallized in a form suitable for high resolution crystallographic investigations. The crystals grow from polyethylene glycol solutions, at pH 6.0, 28 degrees C, and belong to the orthorhombic space group P2(1)2(1)2(1) with unit cell edges a = 73.33, b = 68.86, c = 59.73 A, one protein dimer (32,000 M(r)) per asymmetric unit. Diffraction data have been collected to 3.0 A resolution, and a molecular replacement solution found for Xenopus laevis superoxide dismutase using the bovine enzyme as search model. The crystallographic R-factor corresponding to this solution is 0.412, in the 15.0 3.0 A resolution range. PMID- 8352756 TI - Involvement of acceptor side components of PSII in the regulatory mechanism of Plectonema boryanum grown photoautotrophically under diazotrophic condition. AB - Alternating peaks of photosynthetic activity (P-phase) and nitrogen fixing activity (N-phase) were shown in Plectonema boryanum grown under diazotrophic condition in continuous light. In N-phase photosystem I activity increased by 35 45% and oxygen evolution decreased by 70-80% which was partially restored to 45 55% in the presence of 2,6-dichloro-p-benzoquinone. Thermoluminescence glow curve in P-phase consists of a major band at 25 degrees C which was shifted to 10 degrees C in N-phase. Both these bands are sensitive to DCMU and tetranitromethane. Flash excitation studies with major thermoluminescence band in P and N-phase showed oscillations with same periodicity of four having maxima at 2nd and 6th flashes. On the basis of these observations it is suggested that photosynthetic electron transport under diazotrophic growth condition is regulated by the redox levels of the secondary quinone acceptor QB. PMID- 8352755 TI - Studies on the carbohydrate-binding characteristics of human pulmonary surfactant associated protein A and comparison with two other collectins: mannan-binding protein and conglutinin. AB - The surfactant-associated protein A (SP-A) belongs to the collectin family, a group of C-type lectins encompassing also surfactant-associated protein D, mannan binding protein (MBP) and conglutinin. These proteins all have carbohydrate recognition domains joined to collagen stalks. It seems likely that SP-A, like MBP and conglutinin, may mediate anti-microbial activity through binding to carbohydrates on the microorganisms and collectin receptors on phagocytic cells. We have studied the influence of carbohydrates on the binding of SP-A, MBP and conglutinin to mannan in an enzyme-linked lectin-binding assay. All sugars were of D-configuration, except fucose of which both L- and D-configurations were tested. The order of inhibiting potency on the binding of SP-A was: N acetylmannosamine > L-fucose, maltose > glucose > mannose. The following sugars were non-inhibitory: galactose, D-fucose, glucosamine, mannosamine, galactosamine, N-acetylglucosamine, and N-acetylgalactosamine. The best inhibitor of MBP was N-acetylglucosamine. Otherwise MBP showed a selectivity similar to that of SP-A. Conglutinin binding was inhibited by all the sugars examined except N-acetylgalactosamine. For conglutinin, as for MBP, the best inhibitor was N acetylglucosamine. Normal human SP-A, alveolar-proteinosis SP-A purified by ion exchange chromatography, and alveolar-proteinosis SP-A purified by n-butanol extraction showed no difference in sugar selectivity. The influence of pH and of the calcium concentration was also examined. Organic solvent-extracted SP-A from patients suffering from alveolar proteinosis and normal SP-A showed different sensitivity profiles. PMID- 8352758 TI - Expression and localization of dystrophin in cultured neonatal rat cardiac myocytes. AB - We examined the expression and localization of dystrophin in cultured neonatal rat cardiac myocytes by Western blot analysis and immunohistochemistry using an antidystrophin antibody. Western blot analysis showed a single band with a molecular weight of about 400 kd. Immunohistochemical staining also detected dystrophin in cultured cardiac myocytes, and it was found primarily around the nucleus on day 2 of culture, the area and degree of staining increased on days 4 and 7, and most cells were stained almost entirely on day 14. We conclude that dystrophin also is expressed in cultured neonatal rat cardiac myocytes, and that it increases with time, and extends from the perinuclear area to the whole cell. PMID- 8352759 TI - Primary structure of the factor VIII binding domain of human, porcine and rabbit von Willebrand factor. AB - von Willebrand factor (vWF) binds to Factor VIII (FVIII) and the FVIII binding domain has been localized to the amino-terminal of the vWF subunit. The DNA sequence coding for part of the vWF precursor (provWF) including the FVIII binding domain has been compared in man, pig and rabbit. The sequenced fragment corresponds to nucleotides 2416 to 2886 of the human vWF cDNA and encodes for the last 41 amino acids of the propolypeptide, the cleavage site and the first 116 amino acids of the mature vWF subunit. The homology of the three deduced amino acids sequences is remarkable: 88% between porcine and human and 87% between rabbit and human sequences. Four contiguous amino acids are lacking in the rabbit propolypeptide (-10 to -7) when compared to the human and porcine sequences. The cleavage site of the propolypeptide is conserved in the three species as well as amino acids where mutations in the human gene lead to a binding defect of vWF to FVIII. The Asn-94 N-glycosylation site is present in the human and rabbit sequences but absent in the pig sequence. PMID- 8352760 TI - The mouse iduronate sulfatase gene: identification of a novel transcript. AB - Complementary DNAs, cDNAs, coding for iduronate sulfatase (IDS, E.C.3.1.6.13) have been isolated and characterized in man and mouse. The murine cDNA (MTA16) was highly homologous to the human counterpart. By screening the same mouse thymus cDNA library another cDNA (MTA13) was isolated: it is 1831 bp long and is identical to a part of the MTA16 cDNA in its 5' region, but it is completely divergent in the 3' region. Characterization of the MTA13 mRNA as well as its genomic organization are presented. The results herein reported support the hypothesis that MTA13 and MTA16 mRNAs are encoded by the same gene. PMID- 8352761 TI - Sequence and functional characterization of feline interleukin 2. AB - Since the discovery of its involvement in the pathogenesis of feline immunodeficiency virus infection ("cat AIDS") and feline leukemia virus infection, the role of feline interleukin 2 (IL-2) has been a focus of particular interest. The purpose of this study was to clone feline IL-2 cDNA, as well as synthesize bioactive recombinant feline IL-2. The isolation of cDNA encoding feline IL-2 was carried out using a PCR-based strategy and screening of a feline leukocyte cDNA library. Feline IL-2 consists of 154 amino acids including a putative signal sequence and has 81%, 69%, 60% and 64% identity to human, bovine, murine and rat IL-2, respectively. Feline IL-2 cDNA was expressed in COS-7 cells. The secreted protein has CTLL-4 murine cytotoxic T cell proliferative activity characteristic of authentic IL-2. These data confirm the synthesis of bioactive recombinant feline IL-2. PMID- 8352762 TI - Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen alpha 1 (I) gene expression in human liver fat-storing cells. AB - Hepatic fat-storing cells (FSC) play a key role in the development of fibrosis as a major source of collagen and other extracellular matrix (ECM) proteins in the injured liver. Both experimental and clinical studies have shown that lipid peroxidation is often associated with the development of liver fibrosis. Here we report that exposure of cultured human liver FSC to the pro-oxidant system ascorbate/iron results in an early induction of lipid peroxidation, as monitored in terms of MDA and fluorescent aldehyde/protein adducts production, and in a significant increase of the constitutive expression of procollagen type I mRNA paralleled by the accumulation of the protein in cell culture media. This fibrogenic effect is almost completely abolished by pretreatment of FSC cultures with the antioxidants alpha-tocopherol (Vitamin E) or diphenylphenylendiamine (DPPD). Moreover, treatment of FSC with 1.0 microM 4-hydroxynonenal (HNE), a highly reactive aldehydic end-product of lipid peroxidation, results in a significant stimulation of procollagen type I gene expression and synthesis, suggesting that this aldehyde also exerts profibrogenic activity. These findings indicate that oxidative reactions can directly influence procollagen I gene expression and synthesis in FSC, thus contributing to the development of liver fibrosis. PMID- 8352763 TI - Kinetic study of the thermal denaturation of G actin using differential scanning calorimetry and intrinsic fluorescence spectroscopy. AB - Previous studies of the thermal denaturation of G actin have yielded conflicting results which have led to contradictory interpretations of the denaturation process. In their interpretations, these authors postulated that the thermal denaturation of G actin can be described by thermodynamical equilibrium laws despite the fact that this transition is irreversible. Using differential scanning calorimetry and fluorescence spectroscopy, we now show that thermal denaturation of G actin does not obey to equilibrium thermodynamics, but rather, is a two-step irreversible phenomenon under kinetic control. It can therefore be analyzed using the recently developed Sanchez-Ruiz equations. PMID- 8352764 TI - A basic transthyretin variant (Glu61-->Lys) causes familial amyloidotic polyneuropathy: protein and DNA sequencing and PCR-induced mutation restriction analysis. AB - A new mutation of transthyretin (TTR) has been identified in a patient with late onset familial amyloidotic polyneuropathy (FAP) of Japanese origin. Peptide mapping by reverse-phase high performance liquid chromatography to compare the patient's TTR with normal TTR showed the presence of an abnormal peptide. Amino acid sequence analysis of the peptide (residues 49-61) showed a lysine-for glutamic acid substitution at position 61. This substitution, verified by direct DNA sequencing, was the result of a guanine to adenine change on exon 3 of the TTR gene. A polymerase chain reaction-induced mutation restriction analysis (PCR IMRA) system was established to rapidly detect the missense mutation. TTR-Lys61 is the first variant TTR with a replacement of the acidic with basic amino acid to be found in the amyloid precursor proteins of FAP. PMID- 8352765 TI - Effect of erythroid differentiation factor on maintenance of human hematopoietic cells in co-cultures with allogenic stromal cells. AB - The effect of erythroid differentiation factor (EDF) on the maintenance of human hematopoietic progenitors in a microenvironment was examined by co-culture of adherent- and E rosette-depleted mononuclear cells from the bone marrow (BM) or peripheral blood (PB) with allogenic stromal cells. EDF had no effect on colony formation of erythroid burst-forming units (BFU-E) from the BM cultured without a stromal layer. The number of BFU-E cultured with the stromal layer was decreased less in the presence of EDF than in its absence. This activity of EDF was also observed when the mononuclear cells were separated from the stromal layer by a filter membrane. These data suggest that EDF facilitates maintenance of the number of BFU-E through a humoral factor(s) secreted by the stromal layer. The number of BM erythroid colony-forming units (CFU-E) was decreased on addition of EDF, which promotes differentiation of CFU-E. The number of PB CFU-E was increased irrespective of the presence or absence of EDF over 2 weeks, suggesting that BFU-E, which are more abundant in PB than in BM, differentiate to supply CFU E. However, the addition of EDF resulted in less increase of PB CFU-E, indicating that it inhibited the proliferation of CFU-E progenitors to suppress colony formation. On the other hand, CFU-GM was consistently decreased by addition of EDF to this culture system. These data indicate that EDF acts as a commitment factor and/or a promoter of erythroid progenitors in a hematopoietic microenvironment. PMID- 8352766 TI - The PKC-inhibitor Ro 31-8220 selectively suppresses PMA- and diacylglycerol induced fluid pinocytosis and actin polymerization in PMNs. AB - The PKC-inhibitor Ro 31-8220 inhibits stimulated fluid pinocytosis of human PMNs induced by the PKC-activators phorbol myristate acetate (PMA, IC50 = 1.35 x 10( 6) M) or diacylglycerols (OAG, diC8) by 95%, whereas Ro 31-8220 has no effect on D2O- or fNLPNTL-induced pinocytosis and enhances cytochalasin D- induced pinocytosis. Also formation of F-actin induced by PMA or diacylglycerols is selectively inhibited. The results indicate that a Ro 31-8220 -sensitive PKC is involved in signal transduction for enhanced pinocytosis and F-actin formation in response to one class of stimuli (classical activators of PKC) but not to others. PMID- 8352767 TI - A computational model of the HBK2 potassium channel ion pore. AB - A computational model of the putative ion pore region of the HBK2 potassium channel was developed. Utilizing experimentally derived constraints, conformations corresponding to both the open and closed states of the ion pore were determined. Also, a conformational basis for the different sensitivites of the internal and external tetraethylammonium binding sites has been proposed. The model presented here suggests a role for other regions of the HBK2 protein in determining the ion pore conformation. PMID- 8352768 TI - Identification of peptide:N-glycanase activity in mammalian-derived cultured cells. AB - The recent finding of peptide:N-glycanase (PNGase) in medaka embryos (Seko, A., Kitajima, K., Inoue, Y., & Inoue, S., J.Biol. Chem. 266, 22110 (1991)) raised the question of how widespread is the occurrence of this type of de-N-glycosylating enzyme. In experiments designed to identify PNGase in the mammalian system, we searched for its activity in some cultured cell lines. Incubation of a 14C labeled N-glycopeptide with extracts prepared from cultured cells resulted in producing the free glycan and the peptide. Detailed characterizations of the products, formed upon incubation of a 14C-labeled N-glycopeptide substrate with the enzyme preparation from C3H mouse loose connective tissue-derived L-929 cells, by HPLC, amino acid and carbohydrate composition analyses, and peptide sequence analysis unequivocally established the reaction products to be the free glycan having di-N-acetylchitobiosyl sequence at its reducing end and free peptide in which the originally glycan-linked Asn residue was converted to the Asp residue. This represents the first demonstration of PNGase in mammalian cells and thus PNGase appears to be a very common enzyme expressed in not only plants and bacteria but also a wide range of animals although its functional significance remains to be clarified. PMID- 8352769 TI - A common nuclear factor that binds to the transcriptional control regions of ribosomal protein L5 and 5S rRNA genes. AB - We have examined the binding of chicken nuclear protein to the promoter regions of chicken ribosomal protein L5 and 5S rRNA genes. A nuclear protein was shown to bind to similar sequences in both promoter regions of the L5 gene (-36 to -21) and the internal control region of 5S rRNA gene (56 to 71). Its molecular mass was estimated to be 34 kDa. Competition gel mobility assay showed that the protein is different from the TATA-box binding protein (TBP). The protein may play a role in a transcriptional coordination of the two genes transcribed by different polymerases, RNA polymerase II and III. PMID- 8352770 TI - Position of cyclization in cyclic ADP-ribose. AB - Cyclic adenosine diphosphoribose (cADPR) is a putative second messenger of calcium homeostasis synthesized from NAD by cleavage of the nicotinamide-ribose bond and cyclization of the ribose to the adenine ring. In this study, the ultraviolet absorption spectra of cADPR have been studied as a function of pH and compared to other compounds containing an adenine ring with substitutions at known positions. The results support a structure for cADPR in which cyclization is to position 1 of the adenine ring, rather than to N6, as has been previously proposed. PMID- 8352772 TI - Antibodies specific for human albumin function as blocking antibodies when attached to erythrocyte-bound albumin. AB - Albumin is shown to be firmly bound to human red blood cells using the techniques of flow cytometry, immunoblotting, and complement fixation. The interactions between antibodies attached to the cell bound albumin and the complement system are examined. Antibodies specific for human serum albumin bind to albumin on erythrocytes and activate both homologous and heterologous complement in the absence of hemolysis. Moreover, treatment of erythrocytes with anti-albumin antibodies renders the cells resistant to classical pathway mediated lysis initiated by a passive lysis system. Thus, erythrocyte-bound anti-albumin antibodies appear to function in a manner similar to "blocking" antibodies described in some bactericidal systems. PMID- 8352771 TI - Cyclic AMP-induced transcriptional repression of the insulin-responsive glucose transporter (GLUT4) gene: identification of a promoter region required for down regulation of transcription. AB - The mechanism(s) by which cyclic AMP represses transcription of the GLUT4 gene was investigated. 3T3-L1 preadipocytes were stably transfected with a series of 5' deletion mutants of the mouse GLUT4 gene promoter fused to the bacterial CAT gene and then were induced to differentiate into adipocytes. A method based on reverse transcription/polymerase chain reaction (PCR) amplification was developed and optimized to quantitate expression of CAT mRNA transcripts. Treatment with 8 bromo-cAMP down-regulated the level of CAT mRNA in adipocytes transfected with the -7000/CAT, -785/CAT and -469/CAT constructs, but not the -78/CAT construct. Thus, the regulatory element(s) which mediates transcriptional repression by cAMP resides in the proximal promoter of the GLUT4 gene between positions -469 and 78. Since down-regulation of GLUT4 mRNA is unaffected by inhibitors of protein synthesis, cAMP (and insulin) may activate phosphorylation or dephosphorylation of an existing transcription factor that interacts with the GLUT4 proximal promoter. PMID- 8352773 TI - Glycoprotein 2 of zymogen granule membranes shares immunological cross-reactivity and sequence similarity with phospholipase A2. AB - Glycoprotein 2 (GP2), the major protein of rat pancreatic zymogen granule membranes (ZGMs), cross-reacted with an antiserum against porcine secretory phospholipase A2 (sPLA2). Amino acid sequence comparison showed 45% similarity and 23% identity between porcine PLA2 and the C-terminal portion of GP2. An antiserum to intestinal brush border Ca(2+)-independent PLA2 (bbPLA2) also recognized GP2. The antigenic and sequence similarities between GP2, sPLA2, and bbPLA2 imply that the role of GP2 in cellular function is associated with phospholipid binding and/or hydrolysis. PMID- 8352774 TI - Molecular cloning and sequencing of sulfated glycoprotein-2 cDNA from testis of mouse: implications of two different mRNAs of SGP-2. AB - We cloned a mouse homolog of sulfated glycoprotein-2 (SGP-2) cDNA by screening a mouse testicular cDNA library and its nucleotide sequence was determined. The predicted amino acid sequence of the cDNA shares 93% identity with that of rat SGP-2. The nucleotide sequences of both cDNAs show extensive homology throughout the open reading frames and 3' untranslated regions. The 5' untranslated regions, however, share homology only up to 28 bp upstream from the start codons; the rest of sequences are quite different. DNA sequence homology search to mouse SGP-2 cDNA through the EMBL/GenBank database and a recent study on the genomic organization of rat TRPM-2 gene suggest a possibility that there are at least two different SGP-2 mRNAs as a result of alternative splicing and/or different promoter usage in mouse. PMID- 8352775 TI - Complement component C3-derived neutrophil chemotactic factors purified from exudate of rat carrageenin-induced inflammation. AB - Two neutrophil chemotactic factors have been purified from the exudate of chronic phase of rat carrageenin-induced inflammation. Both the factors were derived from the third component of complement (C3); one was an NH2-terminal fragment (C3a) of alpha chain of C3 and another chemoattractant was a COOH-terminal fragment of beta chain, which was referred to as C3 beta c, on the basis of their molecular masses and NH2-terminal amino acid sequences. C3a exhibits potent chemotactic activity for rat neutrophils, and C3 beta c is a novel basic neutrophil chemoattractant with molecular mass of about 11 kDa, suggesting that both chemoattractants play a role in the neutrophil infiltration into inflammatory site of carrageenin-induced inflammation in rats. PMID- 8352776 TI - The nucleotide exchange rates of rho and rac small GTP-binding proteins are enhanced to different extents by their regulatory protein Smg GDS. AB - Rho p21 and rac p21 small GTP-binding proteins are regulated by the same inhibitory and stimulatory GDP/GTP exchange proteins termed rho GDI and smg GDS, respectively. RhoA p21 and rac1 p21 bind with similar affinities to rho GDI and both proteins also bind with similar affinities to smg GDS. RhoA p21 and rac1 p21 have similar GDP/GTP exchange rates in the absence of rho GDI and smg GDS. The velocity of the GDP/GTP exchange reaction for rhoA p21 was enhanced much more by smg GDS than was the velocity of nucleotide exchange for rac1 p21. In the presence and absence of smg GDS, rho GDI reduced the velocities of these nucleotide exchange reactions of rhoA p21 and rac1 p21 to similar extents. These results suggest that rhoA p21 is activated first followed by rac1 p21 activation in response to extracellular signals. PMID- 8352777 TI - Relationship between aging and susceptibility to protein oxidative damage. AB - The objective of this study was to determine if the susceptibility of tissues to experimental oxidative damage is altered during the aging process. Adult houseflies were X-irradiated at different dosages, when they had reached 0.25 and 0.70 of their average life expectancy. Protein carbonyl content and activity of glucose-6-phosphate dehydrogenase were used as indices of oxidative damage. Fly homogenates as well as the live flies were more susceptible to oxidative damage at the older than at the younger age. PMID- 8352778 TI - beta-Amyloid protein amplifies calcium signalling in central neurons from the adult mouse. AB - The role of beta-amyloid in Alzheimer's disease and its cellular mechanism of action are still unclear. Based on observations that beta-amyloid influences neuronal calcium homeostasis we investigated the effect of the peptide on K(+) induced enhancement of free intracellular calcium in dissociated neurons from adult mice. Preincubation with beta-amyloid fragment 25-35 at concentrations > or = 0.05 mumol/l resulted in marked amplification of the K(+)-induced Ca2+ response. This effect was also observed with fragment 1-40, whereas fragment 1-28 or 12-28 did not affect the Ca2+ response. This preparation therefore presents a valuable model to investigate the action of beta-amyloid ex vivo in individual animals. Our findings suggest a small but consisting destabilizating effect of beta-amyloid on neuronal Ca2+ homeostasis resulting in chronically increased neuronal vulnerability. PMID- 8352779 TI - Identification of three forms of the gamma subunit of G proteins isolated from bovine spleen. AB - We reported previously that G proteins from bovine spleen contain at least five forms of the gamma subunit (designated S1 through S5), among which S1 and S5 have been identified as novel gamma and gamma 2 subunits, respectively. In this study, we identified the other three forms of the gamma subunit, namely, S2, S3 and S4. Amino acid sequences of proteolytic fragments obtained from S2, S3 and S4 coincided exactly with internal sequences of gamma 7, gamma 5 and gamma 2, respectively. However, sequence analysis of undigested S4 revealed that S4 was an N-terminally truncated form of gamma 2, while analysis of the C-terminal fragment by fast atom bombardment mass spectrometry revealed that the C-terminus of S4 seemed to be geranylgeranylated and carboxymethylated as is that of intact gamma 2. Thus, the three types of gamma subunit obtained from bovine spleen were identified as gamma 7, gamma 5, and an N-terminally truncated gamma 2. PMID- 8352780 TI - Ovariectomy decreases the mRNA levels of transforming growth factor-beta 1 and increases the mRNA levels of osteocalcin in rat bone in vivo. AB - Estrogen depletion causes postmenopausal osteoporosis. Here we report that steady state mRNA levels of transforming growth factor-beta 1 (TGF-beta 1) and osteocalcin in bone persistently decreased and increased, respectively, in vivo in estrogen-depleted rats after ovariectomy (OVX). 21 female Wistar rats (7-month old) were randomized and underwent OVX or sham-operation, total RNA was extracted from tibiae and assessed by Northern blot analysis. OVX induced 70-80% decrease in TGF-beta 1 mRNA levels and 2- to 3-fold increase in mRNA levels of osteocalcin compared with controls three weeks after surgery. These changes persisted up to twelve weeks post-operation. OVX caused 15% reduction in femoral bone mineral density and 2-fold elevation in serum osteocalcin levels as early as two weeks post-operation. Moreover, estrogen depletion resulted in marked decrease and increase, respectively, in steady state mRNA levels of TGF-beta 1 and osteocalcin in vitro in osteoblastic rat osteosarcoma cells, ROS 17/2.8. Our results provide the first in vivo evidence that expression of TGF-beta and osteocalcin in bone is reciprocally regulated at the transcriptional level in estrogen deficient OVX rats and suggests that TGF-beta 1 may play a role in estrogen-dependent maintenance of normal bone density. PMID- 8352781 TI - Detection of Zn-binding in domain E of the porcine estradiol receptor. AB - A 32 kDa fragment of the porcine estradiol receptor, which contains the entire hormone-binding domain E and parts of the adjacent domains D and F, binds 65Zn with high affinity. Nonradioactive Zn and Cu are equally potent competitors, Co and Ni are less effective. The capacity for Zn-binding is pH-dependent, it is abolished by the ethoxycarboxylation of imidazole, but remains unimpaired after the modification of sulfhydryls by vinylpyridine. The presence of a HDXXH motif in domain E of the receptor and the significance of its similarity with the HEXXH zinc-binding motif of metallo-proteases are discussed. PMID- 8352782 TI - Identification of a protein product of the myotonic dystrophy gene using peptide specific antibodies. AB - In order to identify the protein product of the recently characterised myotonic dystrophy gene, we have raised an antibody (DMAP1) to a peptide sequence of the predicted gene product. This antibody identifies a novel 52 kDa protein in a range of mouse tissues, and in addition a related 42 kDa protein in brain and heart. A second antibody raised to a different peptide from the same predicted sequence, also identifies the 52 kDa protein, which strongly implies that this 52 kDa protein is a major translation product of the myotonic dystrophy gene. PMID- 8352783 TI - Effect of spermine on mitochondrial matrix calcium in relation to its enhancement of mitochondrial calcium uptake. AB - The mechanism of spermine-induced enhancement of mitochondrial Ca2+ uptake was explored using the fluorescent Ca2+ indicator Fluo-3/AM to measure the free matrix Ca2+ concentration. Simultaneously, the extramitochondrial Ca2+ concentration was registered by a Ca(2+)-ion selective electrode. Spermine lowered the extramitochondrial steady state Ca2+ concentration and at the same time induced a decrease of the intramitochondrial Ca2+ concentration. However, there is a concentration-dependent reversal of the stimulatory action of spermine, which may be explained by the existence of a second, low-affinity binding site for spermine which mediates an inhibition of uptake in spite of the existence of an inwardly directed Ca2+ gradient. PMID- 8352784 TI - Nicotinic acetylcholine receptor mRNAs in myasthenic thymuses: association with intrathymic pathogenesis of myasthenia gravis. AB - Reverse transcription and the polymerase chain reaction showed that the alpha-, beta- and gamma-subunit genes of nicotinic acetylcholine receptor (AChR) in human skeletal muscle were expressed in myasthenia gravis (MG) thymuses (3 thymomas and 7 hyperplastic thymuses). A study of the expression of these subunit mRNAs in a variety of human tissues showed that alpha-subunit mRNA was expressed in human thymus and cerebral cortex, and that all three subunits were expressed only in human child thymus. Our results suggest that a complete AChR similar to extrajunctional (embryonic) muscle AChR is expressed in MG thymuses and that intrathymic AChR might be the primary antigen which induces autoimmune responses to muscle AChR. PMID- 8352785 TI - Effect of spermine on mitochondrial glutathione release. AB - Spermine prevents glutathione release induced in rat liver mitochondria by the combined addition of Ca2+ and phosphate. Spermine also inhibits mitochondrial swelling, membrane potential decrease, oxygen uptake and [14C] sucrose entry stimulated by the above reported agent. Mitochondrial swelling is completely prevented by 25 microM spermine while higher concentrations (100 microM) are required for the full inhibition of glutathione release. Therefore, polyamines decrease the mitochondrial inner membrane permeability and, by preventing mitochondrial glutathione loss, also act as protective agents against oxidative stress. PMID- 8352786 TI - Up-regulation of ETB receptor subtype mRNA by angiotensin II in rat cardiomyocytes. AB - The effect of angiotensin (ANG) II on the expression of endothelin (ET) receptor subtype (ETA, ETB) mRNA in cultured neonatal rat cardiomyocytes was studied. ANG II (10(-7) M) increased steady-state mRNA levels of ETB receptor, but not ETA receptor, during 6-12 hr incubation, whose effect was dose-dependent (10(-9)-10( 7) M). ANG II receptor type-1 (AT1) antagonist (CV-11974) completely inhibited the ANG II-induced up-regulation of ETB receptor, whereas the inhibitory effect by ANG II receptor type-2 (AT2) antagonist (PD 123319) was incomplete. These results suggest that ANG II up-regulates cardiac ETB receptor, predominantly via AT1 receptor. PMID- 8352787 TI - A novel domain sequence of connectin localized at the I band of skeletal muscle sarcomeres: homology to neurofilament subunits. AB - A cDNA of 4.0 kb was cloned from a chicken embryo skeletal muscle cDNA library, using an antibody to muscle elastic protein connectin (titin), the molecular mass of which is estimated to be 3,000 kDa. Immunoelectron microscopy revealed that the antiserum raised against the product of the cDNA expressed in E. coli bound to the epitopes of the connectin filament near the N2 line of chicken breast muscle sarcomeres. The predicted amino acid sequence contains eight immunoglobulin C2 motifs and regions highly homologous with the high and medium molecular weight subunits of neurofilament. In addition, there are regions homologous with desmoplakin, calsequestrin, and calpastatin. PMID- 8352788 TI - Cloning and sequence analysis of the 5'-flanking region of the estrogen sulfotransferase gene: steroid response elements and cell-specific nuclear DNA binding proteins. AB - A 2954 bp region of the guinea pig estrogen sulfotransferase gene was cloned and sequenced including 2888 nt upstream of the cap site. This represents the first cloning of the promoter region of a steroid sulfotransferase gene. The 5' flanking region was found to contain a conventional TATA box variant and sequences homologous to estrogen and glucocorticoid response elements. Gel mobility shift assays detected the presence of nuclear proteins in adrenocortical SW-13 and Y-1 cells that bind specifically to 30 mer DNA sequences containing either estrogen or glucocorticoid response elements. In contrast, gel shift experiments using 3T3 fibroblast cells failed to demonstrate similarly upshifted bands. Block deletion studies indicated that regulation of basal estrogen sulfotransferase promoter activity was located within the first 1000 bp upstream of the transcription initiation site. PMID- 8352789 TI - Stable expression of human endothelin receptors ETA and ETB by transfected baby hamster kidney cells. AB - The cDNAs for human endothelin receptors ETA and ETB were subcloned into the eukaryotic expression vector pMPSV/CMV and transfected, in parallel with plasmids carrying resistances for hygromycin B and puromycin, into baby hamster kidney (BHK) cells. Cell clones constitutively expressing high levels of either receptor were obtained through the combined selective pressure of both antibiotics. This was further confirmed by Northern blot analysis using ETA- or ETB-specific oligonucleotide probes. The calculated KD for endothelin (ET)-1 binding to ETA and ETB were 2.2 x 10(-10) M and 5.3 x 10(-10) M, respectively. Competitive binding experiments using the different ET forms showed the expected isopeptide selective and non-isopeptide-selective profiles for ETA and ETB, respectively. BQ 123, a specific ETA antagonist, competed with ET-1 for binding to ETA but not to ETB. PMID- 8352790 TI - Cloning and sequence analysis of a cDNA encoding tetrameric carbonyl reductase of pig lung. AB - A cDNA for tetrameric carbonyl reductase was cloned from a pig lung cDNA library. The cDNA had an open reading frame encoding a protein of 244 amino acid residues with a predicted monomer molecular weight of 25,985. The authenticity of the cDNA was confirmed by a perfect match of 80 amino acids determined from sequencing of amino-terminus, carboxy-terminus and internal fragments of the purified enzyme. The deduced sequence of the carbonyl reductase shows a similarity to those of the short-chain alcohol dehydrogenase superfamily proteins; notably it had an extensive homology (85% identical residues) with a putative gene product of murine adipocyte. PMID- 8352791 TI - Characterization of histogranin receptors in human peripheral blood lymphocytes. AB - Histogranin (HN), a peptide recently isolated from bovine adrenal medulla, is also present in the spleen. In present studies, specific high affinity binding sites for HN were characterized on membrane preparations of human lymphocytes by radioligand binding. [125I]-[Ser1]HN binding was found to be dependent on time and protein concentration and to be sensitive to trypsin treatment. The binding displayed high affinity (Kd = 1.1 +/- 0.3 nM) and saturability (Bmax = 40.2 +/- 5.0 fmol/mg protein), and it was reversed upon addition of unlabelled [Ser1]HN and closely related peptides. The relative potency of various fragments in displacing [125I][Ser1]HN binding indicated that the active core of the molecule resides inside the C-terminal fragment, HN-(6-15). Interestingly, depressed patients displayed a marked decrease in the binding activity (from 15.4 to 8.55 fmol/mg protein at 0.5 nM of [125I][Ser1]HN). The presence of high affinity HN binding sites on lymphocytes provides evidence for a modulatory role for HN in the regulation of lymphocyte functions. PMID- 8352792 TI - Isolation and identification of a novel peptide from the accessory sex gland of the female house fly, Musca domestica. AB - A peptide of novel structure was isolated from accessory glands of the female house fly, Musca domestica by molecular-weight limit centrifugal ultrafiltration and reversed-phase HPLC. After amino acid and protein sequence analyses, the structure of this peptide was confirmed by chemical synthesis and plasma desorption mass spectral analysis to be Leu-Leu-Asn-Ala-Leu-Pro-Leu-Asp-Ala-Leu Ser-Ser-Leu-Thr-Gly-NH2. The accessory gland peptide stimulated contraction of the house fly oviduct at concentrations of 10(-7) M and above. PMID- 8352793 TI - Basal high blood pressure cosegregates with the loci on chromosome 1 in the F2 generation from crosses between normotensive Wistar Kyoto rats and stroke-prone spontaneously hypertensive rats. AB - We investigated the linkage between high blood pressure (BP) and microsatellite genotypes in the independently produced F2 progenies between Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 2.5, 3 and 5 months before salt loading and after 2 month salt loading. In 2.5, 3 and 5 month-old male and female F2 progenies, blood pressure was significantly higher in homozygotes of the SHRSP allele at the two loci on rat chromosome 1, leukosianine (LSN) and myosin light chain (MYL2), than those of heterozygotes or WKY homozygotes. However, this strong cosegregation was attenuated after salt loading for 2 months. Basal (non salt-loaded) blood pressure strongly cosegregates with the loci on rat chromosome 1 and, therefore, putative gene(s) in this region contribute to the development of basal high blood pressure in SHRSP. PMID- 8352794 TI - Osteogenic protein-1 stimulates proliferation and differentiation of human bone cells in vitro. AB - The effect of recombinant human osteogenic protein-1 (OP-1) on proliferation and alkaline phosphatase (ALP) activity was studied using human bone cells in culture. TE85, osteosarcoma cells with osteoblastic characteristics and normal bone cells derived from mandible (HBM) were used. OP-1 stimulated 3H-thymidine incorporation in a dose dependent manner in TE85 (5-fold over vehicle control at 3-10 ng/ml) and HBM cells (1.8-fold at 100 ng/ml). In TE85 cells, OP-1 also increased cell number (2.4-fold over vehicle control at 3 ng/ml). OP-1 stimulated ALP activity in TE85 cells (4-fold over vehicle control at 30 ng/ml), but moderately inhibited ALP activity in HBM cells (to 67% of vehicle control at 100 ng/ml). Because 1,25(OH)2D3 has been shown to increase ALP activity in many cell types, we also studied if 1,25(OH)2D3 modulates the effects of OP-1 on ALP activity. In the presence of 10(-8) M 1,25(OH)2D3, a biphasic response occurred in TE85 and HBM cells with stimulation of ALP activity at low dose of OP-1 and inhibition at high dose. Thus, the effect of OP-1 on ALP activity appeared to be modulated by 1,25(OH)2D3. Our results suggest that OP-1 could be an important regulator of osteoblast proliferation and differentiation. PMID- 8352795 TI - Cloning and expression in Escherichia coli of Thermotoga neapolitana genes coding for enzymes of carbohydrate substrate degradation. AB - A genomic library of thermophilic anaerobic eubacterium Thermatoga neapolitana was constructed in E. coli using the pTZ19R plasmid vector. Some groups of recombinant clones with different cellulase activities were revealed: clones carrying genes for an 1,4-beta-glucanases, 1,3-beta-glucanases, beta-xylanases, beta-glucosidases and beta-xylosidases. One clone possessing avicelase activity was obtained. Some clones were selected with amylolytic activities toward amylose, amylopectin and pullulan. PMID- 8352796 TI - The elastolytic properties of subtilisin GX from alkalophilic Bacillus sp. strain 6644 provides a means of differentiation from other subtilisins. AB - A serine protease exhibiting high activity in alkaline media was purified from alkalophilic Bacillus strain GX6644. The enzyme, subtilisin GX, has a molecular weight of 25,000 and a pI greater than 9.5. The protease exhibited high elastolytic activity, but unlike most elastin hydrolyzing enzymes, elastin hydrolysis and binding were not inhibited by 0.1 M NaCl. The elastolytic properties of subtilisin GX together with its specificity toward amino acid phenyl esters functionally distinguishes this protease from other subtilisins. However, comparisons of the available amino-terminal sequence of subtilisin GX with subtilisins from alkalophilic and neutrophilic Bacillus species revealed extensive homology. PMID- 8352797 TI - Hela cells proteasome interacts with leucine-rich polypeptides and contains a phosphorylated subunit. AB - The proteasome is a multicatalytic proteinase complex composed of several non identical protein subunits with molecular weights ranging from 20 to 35 kDa. To approach the mechanisms modulating the activity of this protease, we have investigated the possible interaction of this particle with specific polypeptides as well as the phosphorylation status of its subunits. A specific antiserum was used to immunoprecipitate this particle under native conditions. Three major polypeptides, characterized by molecular masses of 53, 59 and 77 kDa co immunoprecipitated specifically with the proteasome. Labelling experiments indicated that these proteins are leucine-rich and contain very few methionine residues. None of them were phosphorylated in vivo in normal cell growth conditions, in contrast to one of the proteasome subunit (30 kDa). These results indicate that, in vivo, the proteasome is probably associated with leucine-rich polypeptides and that this protease is a kinase substrate. PMID- 8352798 TI - Apoptosis induction in 32D cells by IL-3 withdrawal is preceded by a drop in the intracellular calcium level. AB - The 32D murine myeloid cell line is dependent on interleukin-3 (IL-3) for growth in vitro. We show here that IL-3 induces a slow increase in endocellular calcium, which is sizeable two hours after the addition. Withdrawal of the cytokine induces apoptosis, whose classic late events are evident after 16/18 hours, and are preceded by a calcium drop during the first 2/3 hours after IL-3 subtraction. Calcium drop is here proposed as a trigger of the apoptotic process, in agreement with other recently reported findings. PMID- 8352799 TI - Molecular cloning of polymorphic markers on RLGS gel using the spot target cloning method. AB - A new method for target cloning of DNA fragments corresponding to spots on the two-dimensional restriction landmark genomic scanning (RLGS) profile has been developed (targeted spot cloning). We used a Not I restriction trapper to select target DNA fragments from Not I, Eco RV double digests of genomic DNA. The use of the restriction trapper substantially reduces the background clones that are established from the direct recovery of RLGS spot DNA from the two-dimensional gels. Genomic DNA clones were isolated in this study as mouse genome markers for 58 spot loci that were previously characterized using RLGS spot mapping. This method provides a powerful tool for isolating DNA clones after their identification by RLGS system. PMID- 8352800 TI - Inhibitory effect of arachidonic acid on GTPase activating protein is antagonized by 1-stearoyl, 2-arachidonoyl glycerol. AB - The intrinsic GTPase activity of cellular protein p21ras is strongly increased by cytosolic GTPase activating protein (GAP). The activity of this enzyme has been shown to be inhibited by arachidonic acid. We report here that this inhibition is antagonized by the presence of 1-stearoyl, 2-arachidonoyl glycerol. This effect is structure specific and dose dependent, being maximum at 200 micrograms/ml of diacylglycerol (DG). These results suggest that production of DG in response to hormones or growth factors stimulation could indirectly modulate the interaction between p21ras and GAP. PMID- 8352801 TI - The precursor molecule of a V lambda II-immunoglobulin light chain-derived amyloid fibril protein circulates precleaved. AB - The putative precursor molecule of a human AL type amyloid fibril protein was isolated from an ultrafiltrate after hemofiltration. Subsequent separation of this protein was achieved by high performance liquid chromatography (HPLC) after reduction and carboxymethylation of the disulfide bonds. The protein was separated into several fractions which were further analyzed by automatic amino acid sequence determination. It was deduced from the sequence data that the precursor molecule is an immunoglobulin L-chain of the lambda-type. The V-region of this protein is most closely related to the proteins of subgroup II. Internal splits occurred in the molecule after lysine residues in positions 110, 129 and 179. The predominant fragment commences with either serine or alanine in position 9 and extends to a serine in position 65 of the V-region. Tryptic peptides generated from the fragments cover nearly the entire V- and C-region of the L chain, with the exception of positions 1-8, from which no peptide has been isolated. PMID- 8352802 TI - The determinants of the dimeric structure of seminal ribonuclease are located in its N-terminal region. AB - A chimeric cDNA was constructed, coding for the N-terminal region of BS-RNase (residues 1-49) and the C-terminal region of RNase A (residues 50-124). The resulting chimeric DNA was expressed in Escherichia coli and found to code for RNase chains that spontaneously assembled into a covalently dimeric ribonuclease. PMID- 8352803 TI - c-MYC repression of promoter activity through core promoter elements. AB - c-MYC was found to repress expression of the c-myc promoter in a transient assay system. Deletion constructs showed the cis-acting element(s) were common to both the P1 and P2 promoters. Further analysis involving replacement of the P2 TATA box and initiator elements with the SV40 late promoter initiator localized the cis-acting elements to the core promoter. PMID- 8352804 TI - Cloning a novel form of rat PDGF A-chain with a unique 5'-UT: regulation during development and in glomerulonephritis. AB - An unique form of rat platelet-derived growth factor A-chain (PDGF A-chain), with a novel 5' UT region, was cloned from a rat macrophage cDNA library and expressed. In the 5' UT, the homology of the 79 bp sequence adjacent to the ATG codon between rat and human was 92%; however, the homology of the remainder in the 5' UT was less than 30%. RNase mapping indicated this form was differentially expressed during development and immune glomerular injury, and that it probably arose from alternative splicing. We propose that the variant mRNAs reflect different levels of the control of PDGF A-chain expression. PMID- 8352805 TI - Identification of ionizable groups essential for the enzyme catalysis on glutathione S-transferase P. AB - The pH-Vmax/KmGSH plot of glutathione S-transferase P (GST-P) showed a bell shaped profile, indicating bifunctional catalysis for glutathione (GSH) conjugation. The ionization constant (Ke) and the heat of ionization (delta He) of the essential ionizable group in the GSH binding site were measured and the value of pKe1 was 5.9 and that of pKe2, 8.4, while the delta He1 and delta He2 were -0.2 and 7.9 kcal/mole, respectively. In a solvent containing 25% ethanol, pKe1 and pKe2 shifted to the alkaline side by 0.47 and 0.2, respectively. These kinetic results indicated that carboxyl and phenolic groups were ionizable groups essential for the GSH conjugation. Chemical modifications using aminomethane sulfonic acid and N-acetylimidazole supported the results of the kinetic studies. PMID- 8352806 TI - Sp1 interacts with the consensus sequence for Egr-1 gene product with a cellular factor(s) and activates the transcription through this element. AB - We report that Sp1 from nuclear extracts of BRL-3A cells interacts with the consensus DNA sequence for the Egr-1 gene product in an overlapping manner. Purified Sp1 failed to bind to this sequence and with the addition of sub saturating level of nuclear extracts, the binding activity appeared. In Drosophila cells (SL2), exogenously expressed Sp1 activated the transcription through the Egr-1 site. These findings suggest that Sp1 can be targeted to a non Sp1 (Egr-1) site with a cellular factor(s) and can activate the transcription through this element. PMID- 8352807 TI - Mechanism-based inhibitors of serine proteinases based on the Gabriel-Colman rearrangement. AB - Neutrophil-derived mediators such as, for example, the serine proteinase elastase, cathepsin G and proteinase 3, play a critical role in inflammatory lung disease. This report describes the design, synthesis and in vitro inhibitory activity of some novel mechanism-based inhibitors of human leukocyte elastase and cathepsin G. The design of the inhibitors is based on the Gabriel-Colman rearrangement. The behavior of the synthesized compounds toward elastase and cathepsin G with respect to inhibitory prowess, mode of interaction, specificity, etc., has been found to be dependent on the recognition and reactivity elements present in each inhibitor. PMID- 8352808 TI - Monoclonal antibodies against human neurotrophin-3. AB - Hybridomas producing monoclonal antibodies (MoAbs) against human neurotrophin-3 (hNT-3) were established using recombinant hNT-3 produced in CHO cells and E. coli as immunogens. Of the five MoAbs obtained, MoAb 3w3 showed the highest antibody titer and also best neutralized NT-3 activity as measured by the survival of chick embryonic day-8 dorsal root ganglia neurons. A sandwich enzyme immunoassay (EIA) for NT-3 was established with solid phase MoAb 3W3 and the Fab' fragment of MoAb 3W3 conjugated to horseradish peroxidase. The detection limit was 2.7 pg/well of NT-3 and no cross-reactivity with nerve growth factor up to 100 ng/well was observed. Using this EIA system we have screened a variety of cell lines for NT-3 production. Among these tested, only human Burkitt's lymphoma Namalwa cells were found to be producing NT-3. PMID- 8352809 TI - Alteration of DNA binding specificity by nickel (II) substitution in three zinc (II) fingers of transcription factor Sp1. AB - Transcription factor Sp1, which has a DNA binding domain composed of three zinc fingers, binds to GC box (consensus sequence, G/T-GGGCGG-G/A-G/A-C/T) and activates the transcription by RNA polymerase II. Metal substitution of nickel(II) for zinc(II) in Sp1 causes no differences in the mode of protein-DNA interaction. However, sequence preference of Ni(II)Sp1 changes from 5'-GGGGCGGGGC to 5'-GGGGCGTGGC, and is distinct from that of Zn(II)Sp1. The result indicates an important effect of metal-induced folding on sequence-specific recognition of DNA by zinc-finger proteins. PMID- 8352810 TI - pH dependent conformational changes modulate functional activity of the mitochondrial ATPase inhibitor protein. AB - A 12kDa, heat stable protein (IF1) inhibiting hydrolytic activity of submitochondrial particles was purified to electrophoretic homogeneity from buffalo heart mitochondria. Specific activity of the purified fraction was > 5000 units/mg. Maximal inhibition was observed at pH 6.0 and was Mg++ and ATP dependent. Circular dichroism studies showed that the inhibitor peptide undergoes a dramatic, reversible conformational change in response to pH which correlates well with its ability to inhibit ATP hydrolysis catalyzed by inhibitor depleted submitochondrial particles. It is shown for the first time that IF1 with a predominantly beta-sheet component is more efficient at suppressing ATPase activity. PMID- 8352811 TI - Oxygenated cholesterols as ligands for cytosolic-nuclear tumor promoter binding protein: yakkasteroids. AB - Several oxygenated cholesterols and their derivatives (yakkasteroids) were prepared as candidate ligands for cytosolic-nuclear tumor promoter binding protein (CN-TPBP). Among the compounds, a possible natural substance, 3 beta,5 alpha-dihydroxycholestan-6-one (yakkasterone), showed the highest binding affinity to CN-TPBP. It also showed high specificity for binding to CN-TPBP: it does not bind to protein kinase C. Investigation of the structure-activity relationships of yakkasteroids revealed that the structure of the side chain at the 20-position is important for the binding activity to CN-TPBP. PMID- 8352812 TI - Prolactin-independent induction of alpha-lactalbumin gene expression in mammary gland explants from pregnant Balb/c mice. AB - A four-fold increment of alpha-lactalbumin mRNA was induced in mammary gland explants from mid-pregnant Balb/c mice cultured for 24h in media containing insulin, cortisol and T3, and this response was enhanced by 40% with the addition of prolactin. In contrast, elevated beta-casein gene expression was evident only in explants cultured in media with insulin, cortisol, T3 and prolactin. These results suggest that the induction of the alpha-lactalbumin gene was prolactin independent and did not result from retention of endogenous prolactin, or its effects, by the mammary explants. PMID- 8352813 TI - Purification of a 57kDa nuclear matrix protein associated with thiol:protein disulfide oxidoreductase and phospholipase C activities. AB - Proteins of the internal nuclear matrix from chicken liver were fractionated, by chromatographic procedures, in non denaturing conditions. At least two fractions were present with phosphatidylinositol-specific phospholipase C and three with thiol:protein-disulfide oxidoreductase activity. A 57kDa protein was isolated which copurified with both these activities. Partial amino acid sequences showed a high degree of homology with a cytosolic protein previously identified as a phospholipase C and with a microsomal protein identified as a thiol:protein disulfide oxidoreductase. Our finding leaves the question still unanswered of the real function of this protein, which for the first time has been isolated from the nuclear matrix. PMID- 8352814 TI - [New central analgesic-acting triaminopyridines]. AB - New Triaminopyridines with a Central Analgesic Activity 2-Amino-3-((prop-1-en-3 yl)oxycarbonylamino)-6-(4-fluorobenzyla mino) pyridine hydrochloride (D-19050) is a centrally and peripherally acting analgesic with rapid onset, long duration of action and a good therapeutic range. D-19050 can be obtained in a 5-step synthesis starting from 2,6-dichloropyridine. PMID- 8352815 TI - Thiazolidinone congeners as central nervous system active agents. AB - 3-(Benzylidene amino)-2-imino-4-thiazolidinones (IIa-c) synthesized by cyclization of substituted thiosemicarbazones (Ia-c) were converted into 2-amino 3-(substituted benzylamino)-4-thiazolidinones (IIIa-c), 2-imino-3-(alpha-aryl azo benzylidene) amino-4-thiazolidinones (IVa-f) and 2-(2-amino-4-oxo-3 thiazolidinyl)-3-aryl-4-isothiazolidinones (VIa-c), IVa-f were finally converted into 5-(arylamino methyl)-2-imino-3-(alpha-aryl azobenzylidene)-amino-4 thiazolidinones (Va-l). These compounds III, V and VI were evaluated for their monoamine oxidase (MAO) inhibitory activity in vitro and various CNS activities in vivo. Some of the compounds exhibited promising CNS activity. PMID- 8352816 TI - Characterisation of the central nervous depressant activity of a commercially available valerian root extract. AB - The evaluation of a commercially available valerian root extract (Valdispert) revealed pronounced sedative properties in the mouse with respect to a reduction in motility and an increase in the thiopental sleeping-time. A direct comparison with diazepam and chlorpromazine revealed a moderate sedative activity for the tested extract. The extract showed only weak anticonvulsive properties. PMID- 8352817 TI - [The bioequivalence of two nifedipine sustained-release formulations after single administration in steady state]. AB - Investigations into the Bioequivalence of Two Nifedipine Controlled-release Formulations after Single Application and in Steady State. The bioequivalence of nifedipine (CAS 21829-25-4) in controlled-release formulation (Corinfar retard dragees) was tested versus a reference preparation in 22 subjects in a cross-over design after the first dose and in steady state. Compared to the reference, the preparations tested were found to have a relative bioavailability of 0.86 and 0.95, respectively. The bioavailability parameters of the preparations tested did not differ from each other. In particular, the fluctuation indices were noted to be highly similar. In view of the marked prolonged-action effect, a twice-per-day application is possible for the majority of the patients. PMID- 8352818 TI - Kinetics and pharmacodynamic effects of a novel prodrug of N-methyldopamine at single dose in healthy volunteers. AB - Kinetics and cardiovascular effects of SIM2055 (CAS 103878-96-2), the 4-O phosphate of N-methyldopamine (epinine), at single dose by the oral route were studied in 9 healthy adult volunteers (6 women and 3 men) ranging in age from 22 to 39 years. SIM2055 was administered at increasing doses (from 100 to 300 mg). Plasma concentrations of free epinine were not detectable after the 100 mg dose, but were measurable after the 200 mg and 300 mg doses. Pharmacokinetic data suggest that in man SIM2055 is promptly absorbed, quickly hydrolysed to epinine, metabolized to homovanillic acid and 3,4-dihydroxy-phenylacetic acid, conjugated with sulphuric acid and excreted in large amounts into urine. The 24-h urinary recovery of the 3 metabolites considered together, expressed as a percentage of the dose of SIM2055 administered, was 78 +/- 6 with the 100 mg dose, 66 +/- 11 with the 200 mg dose and 55 +/- 6 with the 300 mg dose (mean +/- S. D.). SIM2055 was well tolerated by all subjects. After its administration, the heart rate and the systolic and diastolic blood pressure presented no systemic or clinically significant variations. No substantial changes were observed with the ECG parameters. No subject reported gastric or systemic effects during the period of observation. PMID- 8352819 TI - Competition between deferiprone, desferrioxamine and other chelators for iron and the effect of other metals. AB - Competition for iron between the leading oral iron chelator deferiprone (L1, 1,2 dimethyl-3-hydroxypyrid-4-one) and desferrioxamine (DF), and the effect of other metals has been studied. Visible spectroscopy was used to estimate the displacement of iron from DF-iron(III) and L1-iron(III) complexes, respectively, by varying quantities of up to 100 molar equivalent of a competing metal ion M+ (Mg2+, Al3+, Ca2+, Mn2+, Co2+, Cu2+, Zn2+ and Pb2+) at physiological pH. Copper and aluminium showed the greatest competition against iron, while magnesium, calcium and manganese had little or no effect and the other metals an intermediate effect. DF showed greater selectivity for iron than L1 under these conditions. An analogous series of experiments carried out using a competing chelator of up to 50 molar equivalent in a place of a competing metal ion showed that 8-hydroxyquinoline, diethylenetriamine-pentaacetic acid (DTPA) and tropolone were more effective at displacing iron from DF-Fe and (L1)3Fe complexes than maltol or omadine. Desferrioxamine was the most efficient competitor against L1. Stoichiometric studies of the L1 complexes of aluminium and copper at pH 7.4 using Job Plots, suggested the formation of (L1)3Al and (L1)2Cu complexes, respectively. PMID- 8352820 TI - Erythema formation in magnesium-deficient albino rats. A non-invasive model for the screening of anti-inflammatory agents and oral mineral supplements. AB - The enteral bioavailability of magnesium firmly bound to a fire-proof, inert SiO2 Al2O3 matrix (ground magnesia boats) was studied in magnesium-deficient albino Sprague-Dawley rats, with and without blocking gastric hydrochloric acid secretion with omeprazole. Magnesium was absorbed, although to a small degree, also at anacidity. Pronounced erythema, developing after only some days in hypomagnesemic hypercalcemic rats, are proposed as a non-invasive model for the screening of antiinflammatory substances. Using this model significant protective effects were proven for cromoglycate, polyenthylene glycol 400, and omeprazole; the latter, however, seems more likely to act via a magnesium-sparing mechanism. PMID- 8352821 TI - Pharmacokinetics and pharmacodynamics of naproxen in acute experimental hepatitis. AB - The pharmacokinetics of intravenous naproxen (CAS 22204-53-1) 6 mg kg-1, were studied in Wistar rats under control conditions and 1, 3 and 10 days after the induction of acute hepatitis by a single intraperitoneal injection of galactosamine 375 mg kg-1. In non-intoxicated rats t1/2 was 5.31 +/- 0.90 h, Vd was 0.21 +/- 0.01 l.kg-1, Cl was 17 +/- 5 ml.h-1.kg-1, AUC was 354.4 +/- 8.8 micrograms.h.ml-1 and 99.18 +/- 0.09% of naproxen was bound to plasma proteins. One day after intoxication the liver was considerably damaged; cytochrome P450, the main enzymatic system for naproxen metabolism, was decreased in 90%. Naproxen t1/2 was increased to 11.9 +/- 1.2 h but Vd did not change significantly, therefore clearance was reduced to 37%. Binding to plasma proteins was decreased to 83.21 +/- 0.27%. At day 3 liver function and naproxen pharmacokinetics exhibited a partial recovery, t1/2 was 6.59 +/- 0.92 h and clearance was 12.2 +/- 5 ml.h-1.kg-1 being not significantly different from controls; notwithstanding AUC was still significantly different from that of non-intoxicated rats. 10 days after galactosamine injection all pharmacokinetic parameters, as well as those of liver function, returned to basal levels. The results indicate that acute hepatitis produces an important reduction in naproxen elimination. Changes in naproxen disposition, which exhibit a time course similar to that of liver damage, are mainly determined by a decrease in intrinsic hepatic clearance and in the binding to plasma proteins. PMID- 8352822 TI - High-performance liquid chromatographic analysis of piroxicam and tenoxicam in plasma, blood and buffer solution. Application to pharmacokinetic studies in small laboratory animals. AB - A rapid and sensitive high-performance liquid chromatographic procedure is described for the simultaneous determination of piroxicam (CAS 36322-90-4) and tenoxicam (CAS 59804-37-4) in blood, plasma and buffer solutions used in the equilibrium dialysis studies. The method can be used to measure either piroxicam and tenoxicam in these three fluids using the other as internal standard. A Nucleosil C18 and a mobile phase consisting of an acetonitrile-distilled water acetic acid (58 : 38 : 4) mixture were used. The flow rate was 1 ml/min and the effluent was monitored at 365 nm with 0.02 AUFS (absorbance units full scale). The sensitivities of this method were 0.2 microgram/ml levels of piroxicam and tenoxicam in the plasma, blood and buffer solutions samples. PMID- 8352823 TI - Preparation of a gelatin-binding conjugate containing gold thiomalate. AB - Plasma fibronectin has a range of binding sites, for ligands, including denaturated collagen (gelatin). It has been proposed that this activity may be used for nonimmune drug targeting to sites in the extra-cellular matrix such as the targeting of gold thiomalate to rheumatoid joints. In the present study, a novel conjugate has been developed, consisting of the gold thiomalate bound at high density to the gelatin-binding domain of fibronectin, through a polylysine carrier. Isolation and cross-linking of suitable fragments of fibronectin (relative molecular weights 65 and 52 kDa) to polylysine is followed by conjugation to gold thiomalate on a solid phase, gelatin-agarose affinity absorbent. Although gold thiomalate has the ability to inactivate, the protein gold conjugate produced by this technique retained its gelatin-binding activity. PMID- 8352824 TI - Potentiation of human polymorphonuclear leukocytes respiratory burst and phagocytosis by a standardized liver and spleen fraction of peptides. AB - The effect of Factor AF2 (AF2), a xenogeneic fraction of peptides with a molecular weight of < 10,000 Dalton obtained from livers and spleens of newborn lambs, on the oxygen consumption and the phagocytic activity of human polymorphonuclear leukocytes (PMN) was studied. AF2 increased the oxygen uptake of PMN exposed both to serum-treated zymosan (STZ), a phagocytosable stimulus, and phorbol-myristate-acetate (PMA), a soluble stimulus. The potentiating effect of the drug was dose-dependent and more pronounced when suboptimal amounts of either stimulus were used. The phagocytic activity of PMN, as measured by the rate of mineral oil particles ingestion, was also increased by AF2 in a dose dependent manner. These results suggest that the drug may influence PMN behaviour in at least two ways: 1. by increasing the rate of phagocytosis, and 2. by potentiating the respiratory burst induced by soluble and particulate stimuli. The results are discussed in relation to the beneficial effects of AF2 in cancer patients under chemotherapy or radiation treatment. PMID- 8352825 TI - Synthesis and potential anthelmintic activity of methyl-5-(4-salicyloyl-piperazin 1-yl)-benzimidazole-2-carbamates. AB - A series of methyl-5-(4-salicyloyl-piperazin-1-yl)-benzimidazole-2-carba mates (IX) has been prepared. 5-(4-Salicyloyl-piperazin-1-yl)-2-nitro anilines (VII) have been synthesized starting from 5-piperazino-2-nitro anilines and salicyloyl chlorides. Catalytic reduction of VII with Pd/C, followed by treatment with 1,3 dicarbomethoxy-S-methyl isothiourea, yielded the corresponding carbamates (IX), the anthelmintic activity of which was studied. Compound IXa significantly reduced the numbers of preadults, adults and encysted T. spiralis larvae in experimental mice. PMID- 8352826 TI - [Development of methods for measuring the emptying time of solid and liquid test meals in rat stomachs]. AB - Different methods for experimental measuring the gastric emptying time in the rat have been developed. For the invasive method of measuring the stomach emptying time of a solid test meal containing Amberlite pellets too many animals are necessary. On the other hand, for the non-invasive examination of the emptying of a radioactively marked liquid test meal by scintigraphy the resolution of the gamma-camera is too low. However we were able to develop a non-invasive fluoroscopic method for the simultaneous measurement of the gastric emptying of a solid (10 radiodense markers) and a liquid (0.5 ml diluted contrast medium) test meal. Using this method it was possible to examine the influence of stomach motility stimulating drugs, such as the parasympathomimeticum carbachol and the dopamine antagonist metoclopramide. PMID- 8352827 TI - Studies on the reliability of a novel absorption-lipophilicity approach to interpret the effects of the synthetic surfactants on drug and xenobiotic absorption. AB - Some theoretical principles of the absorption/lipophilicity approach, which attempts to explain the effects of the synthetic surfactants on xenobiotic and drug intestinal absorption, are reviewed and experimentally checked by examining the correlations obtained between "in situ" absorption constants, ka, found in rat colon, and "in vitro" lipophilicity indexes, K', for two compound series (secondary aliphatic amines and phenylalkylamines) in the absence and in the presence of the nonionic surfactant Polysorbate 80, in the intestinal perfusion fluid. Evidence is given for the following actions of the synthetic surfactant: at its critical micelle concentration (CMC), it increases the polarity of the absorbing membrane and, at the same time, it disrupts the aqueous stagnant diffusion layer adjacent to the mucosal barrier. When a supramicellar concentration (SMC) is used, the above actions are almost totally masked by the micellar solubilization of the tested amines, which decreases their absorption constants relative to those found at CMC, as markedly as solute lipophilicity increases. As a consequence of these actions, the correlations between ka and K', which are clearly hyperbolic in free solution, become potential in the presence of the surfactant at its CMC, whereas at SMC a bilinear correlation is obtained. Absorption via lipophilic ionized species seems to take place for both compound series. Mathematical and physicochemical interpretations of this behaviour are outlined, and biopharmaceutical implications of these phenomena are discussed. PMID- 8352828 TI - Techniques of mitosis counting. PMID- 8352829 TI - Residency leave. PMID- 8352830 TI - Genetic counseling for families with inherited susceptibility to breast and ovarian cancer. AB - Efforts are under way to isolate a gene (BRCA1) on chromosome 17q12-21. Mutations in this gene predispose women to breast and ovarian cancer. Women with germline mutations in BRCA1 are estimated to have an 85% lifetime risk of developing breast cancer and an increased but as yet undetermined risk of ovarian cancer. It is estimated that one in 200 to 400 American women may be carriers of BRCA1 mutations. We have identified several families that show linkage between breast and/or ovarian cancer and genetic markers that flank BRCA1. It is now possible, within these linked families, to prospectively identify family members likely to be carrying BRCA1 mutations. Because of profound and immediate clinical ramifications, we offered to provide this information to one such extended family. To provide information to this family, we developed a protocol to address the many issues that arise in the delivery of these services. Although testing for BRCA1 mutation carriers is currently limited to very rare families being analyzed for research purposes, this experience presages the complexities of the much larger scale availability of population screening for BRCA1 mutations, which is likely to become a reality in the next few years. PMID- 8352831 TI - Long-term observations of human immunodeficiency virus-infected chimpanzees. AB - Twenty-seven chimpanzees inoculated with material presumed to contain human immunodeficiency virus (HIV) between June 1983 and February 1985 were studied. The animals were examined on four to six occasions between 1989 and 1992 for serologic, virologic, hematologic, immunophenotypic, as well as clinical signs of HIV infection and compared to five uninfected control animals. The 19 animals that had seroconverted within 244 days of inoculation remained antibody positive, whereas those that did not seroconvert within 244 days of inoculation remained antibody negative 6 to 8 years later. HIV antigen was demonstrated at least once in lymphocyte cultures from 12 of the 19 antibody positive chimpanzees during this period. Nested polymerase chain reaction amplified proviral DNA in lymphocytes from 14 of the 19 animals. No proviral DNA was detected in antibody negative animals. Antibody titers were generally higher in animals from which virus was recovered in lymphocyte cultures [granulocyte-macrophage (GM) titer, 1:8427] compared to virus-negative animals (GM titer, 1:3608). Mean total white blood cell and lymphocyte subtype counts were similar in the HIV-infected animals and uninfected controls. The high antibody levels and Western blot profiles, over periods as long as 9 years in these chimpanzees, suggest continuous stimulation of the immune system by HIV antigen although virus was detected only sporadically in the peripheral blood. No illness suggestive of immunodeficiency was seen. PMID- 8352832 TI - Expert evidence in cases of child abuse. PMID- 8352833 TI - Gene therapy begins. PMID- 8352834 TI - Recovery from neurological deficits following biotin treatment in a biotinidase Km variant. AB - A 15-year-old boy suffered from progressive bilateral optic neuropathy of acute onset at the age of 10 years. Subsequently he developed spastic paraparesis and a predominantly motor type neuro-axonal neuropathy in all limbs. The basic error has been elucidated to be due to an unusual biotinidase Km variant with biphasic enzyme kinetics causing systemic biotin depletion and consequent multiple biotin dependent carboxylase deficiency. After daily oral substitution with 10 mg biotin metabolic derangements subsided rapidly. Follow-up studies over one year after substitution with biotin demonstrated remarkable recovery from part of the previously present neuro-ophthalmological, motor and cognitive deficits. The previously extinguished flash-evoked visual potentials now showed clear responses after six months of substitution with biotin. In contrast with reports in literature, these findings indicated that neurological damage associated with biotinidase deficiency, rather than being permanent, is to some extent reversible. PMID- 8352835 TI - Philosophy of care. A pilot study comparing certified nurse-midwives and physicians. AB - Certified nurse-midwives (CNMs) and physicians (MDs) are thought to differ in philosophy of pregnancy care and childbirth. However, these differences have not been documented quantitatively. This article describes and compares the beliefs and care philosophies of CNMs and MDs toward aspects of antepartum and intrapartum care of low-risk women. The sample included seven CNMs and 10 obstetricians at a large tertiary-care hospital. Using stringent statistical criteria for testing differences between the two groups, significantly more teaching was done by the CNMs than by the MDs. Other differences were all in expected directions. PMID- 8352836 TI - Colour blindness and natural selection: studies in four nomadic tribal groups from Andhra Pradesh, India. AB - 438 males and 369 females from four endogamous nomadic groups of the Yerukala viz. Suvvi, Badda, Uppu and Kunchapuri of Andhra Pradesh (India) were examined for red-green colour blindness using the 15th edition of Isihara's colour blindness chart. The absence of defective colour vision in the Badda Yerukala and very low frequencies among the other groups agree not only with the hypotheses of Post (1962) and Pickford (1963) concerning the operation of natural selection, but corroborates, too, the opinion of Malhotra (1978) that nomads by virtue of their life-style demand good colour vision. PMID- 8352837 TI - Management of alcohol problems: the role of the general practitioner. AB - Some 23% of men and 8% of women in the United Kingdom are consuming alcohol at levels that are of risk to their health, or are experiencing some problems related to their alcohol use. Traditionally, general practitioner efforts have focused on diagnosing and treating patients with a substantial history of dependence, and relatively little attention has been given to early intervention, with at-risk drinkers identified in general practice through screening or case finding programmes. Evidence indicates that early interventions by general practitioners are effective in reducing alcohol consumption among at-risk patients. Further work is still needed on the most effective ways of supporting general practitioners in this task. PMID- 8352838 TI - Evaluation of lithium treatment in alcoholism. AB - In psychiatric practice, lithium prevents manic depressives recidivism. Lithium could also be useful in non-manic-depressive conditions with a reduction of aggression and impulsivity. From the observation that alcoholics often present mood swings and impulsivity, several authors studied the effects of maintenance doses of lithium on alcohol intake and the depressive symptoms of alcoholics. This article reviews all the published controlled and uncontrolled studies on the effects of lithium in chronic alcoholics. Wren, Kline and colleagues firs demonstrated that lithium treatment could significantly decrease the number of disabling alcoholic episodes and that its effect was independent of an effect on the depressive symptoms. These initial optimistic conclusions were not confirmed by later controlled studies involving a larger number of patients. Most of the recent studies failed to demonstrate a significant effect of lithium on the depressive symptoms of alcoholics. Thus, it is now established that lithium is not an effective treatment of affective disorders in alcoholics. The latest published studies also suggest that lithium treatment does not decrease alcohol intake or craving for alcohol in either depressed or non-depressed alcoholics. PMID- 8352839 TI - Anxiogenic responses of rats on withdrawal from chronic ethanol treatment: effects of tianeptine. AB - Rats were fed a liquid diet with concentrations of ethanol increasing over 2 weeks and then maintained for 4 weeks to give a mean ethanol intake of 11.6 g/kg/day. They were withdrawn from ethanol for 12 hr and tested in two tests of anxiety, the social interaction and elevated plus-maze tests, and in the holeboard, which provides measures of exploration and motor activity. Compared with control animals that had received the liquid diet without ethanol, the rats withdrawn from ethanol showed significant reductions in social interaction, in the percentage of entries onto, and time spent on, the open arms of the plus maze, and in measures of general activity in all three tests. Tianeptine, a tricyclic antidepressant which increases 5-HT uptake, reversed the anxiogenic responses and the hypoactivity detected in the social interaction test, but was without significant effect in the other tests. PMID- 8352840 TI - Excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone in the urine of rats following acute and chronic administration of ethanol. AB - Recent studies have shown that xenobiotics which induce oxidative stress result in an increased production and excretion of acetaldehyde (ACT), formaldehyde (FA), acetone (ACON) and malondialdehyde (MDA) in the urine of rats. We have therefore examined the effect of acute and chronic ethanol administration on the excretion of these four lipid metabolites in female Sprague-Dawley rats. Urine samples were collected over dry ice for 6 hr time periods. Aliquots of urine were derivatized with 2,4-dinitrophenylhydrazine HCl, and extracted with n-pentane. High pressure lipid chromatogrpahy (HPLC) was used to quantitate and the hydrazones of the four lipid metabolite products. Following a single, oral, acute dose of 5 g ethanol/kg, urinary excretion of ACT increased approximately 5.8-fold from 6 to 12 hr posttreatment, and decreased thereafter. FA excretion decreased by approximately 50% from 0 to 12 hr, returned to control values in the 18-24 hr urine samples, and was 1.3-fold greater than control values at 42-48 hr. ACON increased 3.1-fold over control values from 0 to 30 hr and remained elevated throughout the remaining 18 hr of the study. The excretion of MDA increased approximately 1.5-fold from 18 to 36 hr, then remained constant through the 48 hr time point. In a separate series of experiments, a chronic oral dose of 0.5 g ethanol/kg was administered to rats for 10 consecutive days and the urinary excretion of the lipid metabolites MDA, FA, ACT and ACON was examined for 11 days, beginning with the first day of ethanol administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352841 TI - Rates of protein synthesis in different regions of the normotensive and hypertrophied heart in response to acute alcohol toxicity. AB - The objective of study was (a) to investigate whether protein synthesis in different regions of the heart (i.e. left and right atria, left and right ventricles) expressed equal sensitivity to acute ethanol dosage, and (b) to ascertain whether concomitant cardiac abnormalities (i.e. experimental hypertrophic heart disease) exacerbated these responses. Acute ethanol dosage (75 mmol/kg body weight, i.p.) to mature male Wistar rats reduced the fractional rate of protein synthesis (ks, %/day) in all regions (atria and ventricles) of the normal and overloaded (30 days aortic constricted) hearts. The responses in ks were variable. In normal heart, the atrial tissues showed a slightly greater decrease in ks (approx. -30%) when compared to the ventricular regions (approx 20%). The most pronounced effects occurred in the hypertrophied left ventricular tissues where the depressive effects of ethanol on the rate of protein synthesis were potentiated in the presence of hypertrophy (ks reduced by approx 40%). Other regions of the overloaded heart did not show additional sensitivity to the effects of ethanol on protein synthesis in the presence of chronic hypertension. In conclusion, the deleterious effects of ethanol on the left ventricle are additive in the presence of chronic hypertrophy. These results may have important implications for other cardiac abnormalities where there is also concomitant ethanol exposure. PMID- 8352842 TI - Relative and combined roles of ethanol and protein malnutrition on muscle zinc, potassium, copper, iron, and magnesium. AB - The aim of the present study is to analyse the relative and combined effects of ethanol and protein malnutrition on muscle zinc, copper, iron, potassium, and magnesium in ethanol-fed rats. The study was performed in 32 animals divided into four groups, fed with the Lieber-DeCarli control, 36% ethanol, 2% protein, and 36% ethanol 2% protein containing diets, respectively. Right gastrocnemius muscle was removed 2 months later, and was studied both chemically and histochemical morphometrically. Both muscle zinc and potassium, but not copper nor iron nor magnesium, were significantly decreased in the protein-deprived, ethanol-fed animals, the main effect of these variations being attributable to ethanol rather than to protein deprivation. However, coexisting protein deprivation aggravated the decrease in both muscle zinc and potassium. Both muscle zinc and potassium were significantly related to serum albumin, weight loss, and type IIb fibre atrophy; and muscle zinc, in addition, to the decrease in type IIb fibre proportion. Therefore, a decrease in muscle content of both elements is related to histochemical-morphometrical changes observed in alcoholic myopathy. In addition, both ethanol and protein deficiency exerted independent, highly significant effects both on type IIb fibre atrophy and proportion. PMID- 8352843 TI - Tumour necrosis factor, interleukin-1 and interleukin-6 in alcoholic cirrhosis. AB - The existence of a cellular immune deficit in alcoholic cirrhosis, and the alterations described in cytokine synthesis in this disease, led us to compare serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 in a group of 33 patients with alcoholic cirrhosis (classified according to the Child-Pugh grade of severity of liver disease) and 43 healthy volunteers. Serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 were significantly raised in alcoholic cirrhosis patients, with no significant differences between patients with liver disease of different grades of severity. The results suggest that cirrhosis involves the activation of the monocyte-macrophage system, which may contribute to the progression of the disease and its clinical manifestations. PMID- 8352844 TI - Litonit: evaluation of clinical effectiveness. AB - Clinical data are presented on a new anti-alcoholic drug, litonit. A substantial reduction in the pathological addiction to alcohol takes place under the effect of litonit, and a stable aversive reaction to alcohol develops. The new drug is distinguished by its low toxicity, good tolerance, and its failure to cause disorders of the liver and kidneys even after chronic administration. PMID- 8352845 TI - A feature of alcoholic Wernicke's encephalopathy favourable to the maintenance of memory function: vomiting. AB - Outcome in terms of progression of Korsakoff's psychosis is known to be unlikely when the preceding thiamin deficiency syndrome, Wernicke's encephalopathy, does not follow heavy alcohol use. There is evidence that alcohol potentiates thiamin related brain damage. It is argued here that in heavy drinkers, if vomiting precedes the onset of the encephalopathy, then the latter might develop at a time when tissue alcohol levels are close to zero. Any progression to Korsakoff's psychosis could then be associated with less or even no impairment. This outcome would not be expected if ingestion of alcohol continued during the vomiting stage. In a follow-up study of 61 cases of alcoholic Wernicke's encephalopathy, these concepts are given some support by the results obtained. PMID- 8352846 TI - Severity of alcohol dependence; rating by patient records. AB - A method to assess the severity of alcohol dependence by rating patient records was developed using the items of the 'alcohol abuse' subscale of the Swedish version of the Alcohol Use Inventory (AVI). The records of 37 alcoholics were rated and the scores were compared with the patients' self-report scores of the AVI and clinical assessments based on the structured clinical interview for DSM III-R (SCID). The inter-rater reliability was rs = 0.88. The correlations between the record ratings and the alcoholics' self-ratings were rs = 0.77 for both raters and 0.55-0.57 between the record ratings and the total SCID-scores. The correlations between the self-ratings and SCID-scores were rs = 0.90. It is suggested that this method may facilitate record-based follow-up studies of alcoholics. PMID- 8352847 TI - End of life care in Duchenne muscular dystrophy. AB - End of life care for patients with Duchenne muscular dystrophy (DMD) has become increasingly complex because of new technologies, changes in medical personnel over periods of time, emergence of home health care systems, and increasing patient and family autonomy in decision-making. In this review, we discuss the medical problems, particularly respiratory and cardiac failure, faced by DMD patients. Current concepts concerning the evaluation and options for treatment of these problems are presented as well as the ethical issues involved in the care of the DMD patient. These issues include the medical indications for treatment, patient preferences, quality-of-life issues, and contextual features related to legal, institutional, religious, geographic, cultural, social, and financial factors. We also present our experience at Loma Linda University Medical Center over the past 10 years in the development of a home mechanical ventilation program for DMD patients and an algorithm for the evaluation of these patients. Many patients with DMD do well on long-term ventilation, but some find that their quality of life is less than desirable and choose to discontinue this method of life-prolongation. Many of these new options are very expensive, making the decision to use them a difficult one. Ultimately, these are societal issues that require clear reflection on matters of resource allocation that should be performed by health care professionals, citizens, and health planners. PMID- 8352848 TI - Influence of gestational age, birth weight, and asphyxia on neonatal neurobehavioral performance. AB - The objectives of this study were to determine the influence of birth weight, gestational age, and asphyxia on neurobehavioral performance at 40 weeks conceptional age, and to demonstrate that this performance may differ in preterm high-risk infants when using low-risk preterm rather than healthy term infant norms. A cross-sectional comparative design was used to compare neurologic behavior in healthy and high-risk newborns at 40 weeks conceptional age using the Einstein Neonatal Neurobehavioral Assessment Scale. Seventy-four high-risk newborns were selected from a consecutive sample of asphyxiated, very-low-birth weight, and small-for-gestational-age neonates. Controls did not fulfill any of the high-risk criteria and had no pre- or perinatal complications. There were 37 healthy term and 17 low-risk preterm controls. Statistically significant differences occurred between high-risk newborns and term controls for the total score (P < .001) as well as for most individual items (P < .05). Analysis of high risk subgroups revealed that small-for-gestational-age and term asphyxiated newborns had the most abnormal responses. When comparing test performance between preterm high-risk and term controls, the majority of test items achieved significance (P < .05); however, when compared to low-risk preterm controls, fewer items were abnormal, and the probability level on abnormal items was less significant than expected. This disparity in interpretation of neurobehavioral status in preterm high-risk neonates using a preterm versus term reference sample warrants further investigation. Appropriate normative standards for preterm infants require definition because it may increase the utility of the neonatal neurologic examination and its prognostic value. PMID- 8352849 TI - Prospective study of spinal muscular atrophy before age 6 years. DCN/SMA Group. AB - Spinal muscular atrophy (SMA) is a common neuromuscular disorder of childhood, associated with a high mortality rate during the first 2 years of life. Most practitioners expect patients with SMA to follow a progressive course with loss of muscle strength and function over 2-10 years. Counselling sessions with parents frequently emphasize the high mortality rate and risk for respiratory failure. The progressive nature of SMA has been attributed to the loss of motor neurons. Fifty-eight children, ages 6 years and younger, were examined between January, 1987, and April, 1992, as part of a large, multicenter collaborative study of SMA. Muscle function was evaluated at regular intervals using a standardized protocol that was demonstrated to be reliable. We determined a prevalence of 56% for tongue fasciculations, a prevalence of 22% for facial weakness, and persistent deep tendon reflexes in one patient. Improved motor function and acquired milestones during the study were documented. This work should contribute toward a better understanding of the natural history of SMA. PMID- 8352850 TI - MRI assessment of myelination patterns in high-risk infants. AB - Magnetic resonance imaging (MRI) was used in high-risk infants to assess the myelination process and its relationship with neurologic outcome. The time period when delayed myelination is best detected by MRI was also studied. MRI was performed in 39 high-risk infants (i.e., preterm infants, infants with respiratory distress syndrome, or with neonatal convulsions and asphyxia). In 10 of 11 infants with normal development, MRI revealed a normal myelination pattern before 2 months of age, and in 11 of 13 infants after 2 months of age. Conversely, in infants with poor outcomes, MRI demonstrated delayed myelination patterns in only 1 of 4 infants before 2 months of age but in 9 of 11 infants after 2 months of age. In patients with poor outcomes, delayed myelination was found more frequently after rather than before 2 months of age. These findings demonstrate that delayed myelination detected by MRI is useful in predicting the neurologic outcome of high-risk infants, especially after 2 months of age. PMID- 8352851 TI - Congenital adrenal hyperplasia and cerebral lateralizations. AB - Handedness, immunologic disorders, language lateralization, reading fluency, and visual-motor achievements were assessed in 25 patients with congenital adrenal hyperplasia and age-matched right- and left-handed normal controls. An increased rate of left-handedness in the congenital adrenal hyperplasia group was evident. The prevalence of immunologic disorders, dichotic listening patterns, and visual motor/reading achievement ratio were more similar to left-handed and significantly different from right-handed controls. Females appeared to be more affected than males in some of the functions. These results partly support the hypothesis of intrauterine androgenic effects on hemispheric function, but not to the extent of a complete lateralization shift. PMID- 8352852 TI - Abnormal cortical excitability in Rett syndrome. AB - Visual and somatosensory evoked potentials (VEPs and SEPs) were studied in 9 patients with Rett syndrome and compared with those in 6 patients with photosensitive progressive myoclonus epilepsy (PPME). In Rett syndrome, a giant III-IV amplitude of VEPs was present in 8 patients, although none exhibited giant II-III amplitudes. Four of 6 patients with Rett syndrome who demonstrated giant SEPs did not have a C reflex. Conversely, the patients with PPME demonstrated giant II-III and III-IV amplitudes in VEPs, and giant SEPs with concurrent positive C reflexes. It is concluded that the mechanism of altered cortical excitability in Rett syndrome is different from that in PPME. PMID- 8352853 TI - Asymptomatic Becker muscular dystrophy: expression of dystrophin and dystrophin related protein. AB - The expression of dystrophin and a dystrophin-related protein in muscle from 3 asymptomatic Becker muscular dystrophy patients is reported. Histology demonstrated moderate variation in fiber size with clustered basophilic regenerating fibers. Immunostaining for dystrophin revealed a patchy appearance on most fibers, but never on clustered regenerating fibers. Those regenerating fibers did, however, have positive immunoreactivity to a dystrophin-related protein. It is speculated that overexpression of the dystrophin-related protein in regenerating muscle fibers may contribute to the slow progression of muscle weakness or atrophy. PMID- 8352854 TI - Late fetal pontine destruction. AB - A child with an absent pons is described who died 8 weeks after birth. At postmortem examination, the defect was consistent with a vascular event in the last trimester. PMID- 8352855 TI - Pyruvate dehydrogenase deficiency: clinical and biochemical diagnosis. AB - A female neonate with pyruvate dehydrogenase (PDH) deficiency is presented with clinical, radiologic, biochemical, neuropathologic, and molecular genetic data. She was dysmorphic, with a high forehead, lowset ears, thin upper lip, upturned nose, and rhizomelic limbs. Cranial MRI revealed severe cortical atrophy, ventricular dilatation, and corpus callosum agenesis. Pyruvate and lactate levels were increased in CSF and blood. Urinary organic acid profile was compatible with PDH deficiency. PDH activity was normal in fibroblasts, lymphocytes, and muscle. The PDH E1-alpha gene was sequenced and a single base mutation was found within the regulatory phosphorylation site in exon 10. It is postulated that this mutation causes a cerebral form of PDH deficiency. Tissue-specific expression of the disease could be explained by differential X chromosome inactivation because the PDH E1-alpha gene is located on this chromosome. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF. PMID- 8352856 TI - Dermoid of cavernous sinus resulting in isolated oculomotor nerve palsy. AB - Intracranial dermoid cysts and acquired oculomotor nerve palsies are individually rare in childhood. This report describes a 4-year-old boy with acute oculomotor nerve palsy and pupillary sparing secondary to a dermoid within the lateral wall of the cavernous sinus. The clinical signs resolved after complete surgical excision of the tumor with no evidence of recurrence on computed tomography 1 year later. This is the first case report in childhood of a dermoid within the cavernous sinus and of an isolated oculomotor nerve palsy due to a dermoid cyst. PMID- 8352857 TI - Cerebral edema in acute hepatic failure: clinicopathologic correlation. AB - A child developed acute fulminant viral hepatitis and cerebral edema confirmed on postmortem examination. Clinical evidence of herniation, effacement of cortical sulci on computed tomography, and elevated cerebrospinal fluid pressure preceded complicating terminal events, demonstrated that cerebral edema was associated with acute hepatic failure, rather than complicating factors, and led to the patient's death. The mechanism is unknown. PMID- 8352858 TI - Cerebral malformations in Carpenter syndrome. AB - The inherited forms of craniosynostosis can be divided into 4 groups: isolated craniosynostosis, craniosynostosis with syndactyly, craniosynostosis with polydactyly and syndactyly, and craniosynostosis with other somatic abnormalities. Acrocephalopolysyndactyly or Carpenter syndrome consists of craniosynostosis, short fingers, soft tissue syndactyly, preaxial polydactyly, congenital heart disease, hypogenitalism, obesity, and umbilical hernia. As many as three-fourths of the patients have some degree of intellectual impairment. The etiology of mental retardation in this syndrome has not been explored. A patient is reported with the features of Carpenter syndrome who has profound developmental delay and cerebral malformations demonstrated by magnetic resonance imaging and computed tomography. Because mental retardation is not an invariable feature of this syndrome or other craniosynostosis syndromes, neuroradiologic examination may help in predicting the intellectual outcome in these patients. PMID- 8352859 TI - MRI in neonatal dural sinus thrombosis. AB - Dural sinus thrombosis in the newborn period is a rare but underrecognized condition which may cause seizures, macrocephaly, lethargy, and respiratory depression. A 10-day-old term infant with no pre- or perinatal risk factors for thrombosis presented with seizures and was found to have dural sinus thrombosis on computed tomography and magnetic resonance imaging (MRI). One week later, MRI revealed partial resolution and 3 weeks later disclosed a complete resolution of the thrombosis. Clinicians should consider the diagnosis of neonatal dural sinus thrombosis in infants presenting with seizures and/or increased intracranial pressure even in the absence of risk factors or when the cranial computed tomography is normal. MRI is the most sensitive diagnostic tool to establish the diagnosis and permit a noninvasive follow-up, contributing to our understanding of the natural history, associated pathology, and prognosis of this condition. PMID- 8352860 TI - Myopathy with abnormal distribution of dystrophin, growth retardation, mental retardation, and hypospadia. AB - A 9-year-old boy with severe growth retardation, mild mental retardation, and hypospadia had a high serum CK level without muscle weakness and atrophy. Muscle biopsy revealed a moderate variation in fiber size with a few necrotic and scattered regenerating fibers. Although muscle membranes were clearly stained by immunostaining with antibody to dystrophin, N-terminal region (2-5E2), fibers in groups revealed striking, intense staining with the other antibody, C-terminal region (4C5), suggesting some aberration of the dystrophin gene near the C terminal area. His unique clinical features, as well as myopathy, are reported, although further study is necessary to clarify the relationship between the anomalous conditions and dystrophin abnormalities. PMID- 8352861 TI - Mevalonic aciduria in 3 siblings: a new recognizable metabolic encephalopathy. AB - Mevalonic aciduria, due to mevalonate kinase deficiency, is the first recognized defect in the biosynthesis of cholesterol and isoprenoids. Very few patients with this disorder have been reported. Three siblings born from consanguineous parents are reported. Several clinical signs were present in all 3 children, including failure-to-thrive, susceptibility to infections, hepatosplenomegaly, cataract, and psychomotor retardation. Dysmorphic features were more apparent in the two older siblings. Urinary organic acid analysis by gas chromatography/mass spectrometry invariably revealed a high urinary excretion rate of mevalonic acid. Mevalonate kinase activity assayed in fibroblasts was very low. Diagnosis of this very rare disease may be suspected simply on clinical evidence; it is confirmed by abnormal excretion of mevalonic acid. PMID- 8352862 TI - Autosomal recessive cerebellar hypoplasia. PMID- 8352863 TI - The health of the Inuit of North America. A bibliography from the earliest times through 1990. PMID- 8352864 TI - Tensions within the academic health center. AB - A variety of forces are converging to unbalance the internal environment of the academic health center, and the dean of the medical school sits uneasily in the resulting vortex of conflicting needs and demands. For example, the introduction of Medicare in 1965 profoundly changed the size and complexity of medical school departments and greatly stimulated the growth of hospitals. More stresses have come from rising health care expectations of the public; the replacement of free for-service indemnity health care by managed care and vertically integrated health care systems; the proliferation of academic specialties and subspecialties; and the recent growth in the academic medical center, which is seen as a threat to the academic integrity of the university. Within the medical school there are tensions between basic and clinical research, between education and research, between education and clinical practice, and between the dean and department chairs over allocation of resources. Perhaps the most complex tensions exist between the medical school dean and the academic hospital director. The overarching tension in the academic health center results from striving to balance the need to fulfill academic goals with the need to fill hospital beds to maintain financial solvency. This tension will not lessen so long as there is no common vision for the academic health center as a whole, and will probably increase with the forthcoming changes in health care reform. The dean and the hospital director must forge a strong alliance, and the hospital must realize that for its continuing success, it must support the academic program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352865 TI - Three views on faculty tenure in medical schools. AB - Three distinguished academicians share their thoughts on tenure and its future in academic medicine. Paul J. Friedman, from the University of California, San Diego, School of Medicine, explains and defends tenure as practiced in medical schools. He examines the question of giving tenure to clinical faculty, explains posttenure academic review, reports that the impending end of mandatory retirement will not have a significant effect on faculty turnover, and suggests that medical schools make the status of emeritus faculty more attractive. Next, Gail H. Cassell, from the University of Alabama School of Medicine, examines various beliefs about tenure and tenured faculty in the light of available studies, and concludes that many of the negative "myths" about the effect of tenure (e.g., promoting mediocrity and discouraging productivity) are not borne out by research findings. While she supports tenure, she maintains that better criteria are needed for awarding it; that the evaluation of faculty members' teaching needs much improvement; and that more research on tenure is needed. Finally, Richard A. Cooper, from the Medical College of Wisconsin, states that tenure should not continue, because the purposes of tenure (e.g., ensuring freedom of expression; providing long-term financial security and stability) should be and can be accomplished in other ways for all faculty, not just tenured faculty. A different system is needed, one that respects the value of all faculty, that responds to their diverse objectives, is fiscally responsible, and fosters the continuing culture and vitality of medical schools.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352866 TI - Community partnerships: educational linkages to increase the number of primary care practitioners. AB - The Community Partnerships initiative is focused on the creation of academic, non hospital community health centers shaped by people and institutions at the local level. In our view, public policy-makers need such positive ideas and programs to support--things to be for rather than against. Incessant lamenting about the problems of the health care system will change the system less than will positive programs shaped and supported by the people whose needs they serve. All of us in medical education recognize the need for change in medical education. The Community Partnerships program represents one strategy for change that brings communities directly into the sphere of influence and enables them to enhance the relevance of the educational experience for health professions students. PMID- 8352867 TI - A national consensus on the essential international-health curriculum for medical schools. International Health Medical Education Consortium. PMID- 8352868 TI - Biomedical research training must remain a priority. PMID- 8352869 TI - Omitting the obvious. PMID- 8352870 TI - How one school obtained the benefits of problem-based learning without revolution. PMID- 8352871 TI - Providing clinical experience to first-year students. PMID- 8352872 TI - Take students' course evaluations with a grain of salt! PMID- 8352873 TI - Residents' desire for more clinical ethics education. PMID- 8352874 TI - Performances on the NBME I, II, and III by medical students in the problem-based learning and conventional tracks at the University of New Mexico. AB - BACKGROUND: Problem-based learning curricula are growing in popularity, and questions have been raised about the appropriateness of standardized examinations, such as the National Board of Medical Examiners (NBME) Parts I, II, and III examinations, for assessing students in these new curricula. METHOD: Data on students' performances on the NBME I were analyzed for 508 graduates of the conventional track and 167 graduates of the problem-based Primary Care Curriculum (PCC) track at the University of New Mexico School of Medicine from the classes of 1983-1992; on NBME II, for 447 and 144 graduates, respectively (classes of 1983-1991); and on NBME III, for 313 and 100 graduates, respectively (classes of 1983-1989). The analyses also included data on the students' total Medical College Admission Test (MCAT) scores, undergraduate science grade-point averages (SGPAs), and admission subgroups within tracks. The statistical methods included analysis of covariance, Student's t-test, and the Fisher exact test. RESULTS: The students who had requested the PCC track but had been randomized into the conventional track had the highest mean scores on all the study variables (for 34 students, 521 on the NBME I, and for 19 students, 551 on the NMBE III). The high risk students who had requested but had not been accepted into the PCC track seemed to benefit from the highly structured conventional track with regard to their NMBE I performances (467 for 18 students). The PCC students--both those who had been randomized into the PCC and those who had been selected into the PCC- had significantly lower mean scores on the NBME I (455 for 85 students and 463 for 82 students compared with 505 for the 439 students who chose the conventional track), but significantly higher mean scores on the NBME III (521 for 38 students and 522 for 62 students compared with 483 for the seven high-risk students and 487 for the 276 students who chose the conventional track). For both tracks, strong relationships were found among the scores on the three NBME examinations. For the PCC students, significantly weaker relationships were found between mean SGPAs and mean scores on the NBME I, II, and III. For both tracks, MCAT scores, especially in the lowest and highest ranges, were most predictive of performances on the NBME I and II. CONCLUSION: In the short run, the more teacher-centered and structured conventional curriculum better prepared the students for the NBME I, while in the long run, the more student-centered problem-based curriculum better prepared the students for the NBME III: PMID- 8352875 TI - Physicians' knowledge of genetics and genetic tests. AB - PURPOSE: To assess primary care physicians' and psychiatrists' knowledge of genetics and genetic tests and the factors associated with differences in these physicians' knowledge. METHOD: Questionnaires were mailed in 1991 to 1,795 primary care physicians (family physicians, internists, pediatricians, obstetrician-gynecologists) and psychiatrists who had graduated from medical school between 1950 and 1985 (67.6% of the sample had graduated after 1970) and who were members of professional societies. The questions elicited demographic and practice characteristics as well as knowledge of genetics concepts and facts and awareness of the availability of genetic tests. To validate the questionnaire, 360 medical geneticists and genetic counselors received questionnaires. Statistical analysis involved arc-sine function transformation, t tests, analyses of variance, F-tests, Tukey's HSD, and stepwise multiple regression. RESULTS: A total of 1,140 (64.8%) of the non-geneticist physicians responded. They correctly answered an average of 73.9%, SD, 13.9%, of the knowledge items, compared with 94.6%, SD, 4.2%, for the genetics professionals (p < .001). The most significant predictors of knowledge were recency of graduation from medical school and practicing in primary care specialties in which exposure to genetics problems is likely. Other significant predictors (from most to least important) were graduation from a U.S. medical school, willingness to adopt a new predictive test before it becomes standard practice, not using pharmaceutical companies as a source of information about new medical practices, and taking a required genetics course in medical school. CONCLUSIONS: The results suggest that knowledge of genetics and genetic tests is increasing among physicians, particularly among more recent graduates and physicians who are exposed to genetics problems in their practices, but deficiencies remain. Although a medical school course in genetics may improve knowledge, it is not sufficient. Greater emphasis is needed at all levels of medical education to reduce the chance of physician error as more genetic tests become available. PMID- 8352876 TI - Correlations between graduates' performances as first-year residents and their performances as medical students. AB - PURPOSE: To correlate graduates' performances as first-year residents with their performances as medical students, particularly their performances as seniors on a clinical skills examination using standardized patients. METHOD: Residency directors were asked to rate the first-year performances of the 232 graduates from the classes of 1989-1991 of the Brown University School of Medicine. Pearson correlation coefficients were calculated for the relationships between these ratings and the two scores (for data collection and interpersonal skills) that the graduates had received in their senior year on a clinical skills examination using standardized patients. Correlations were also calculated between the residency ratings and the graduates' preclinical and clinical course grades and scores on Parts I and II of the National Board of Medical Examiners (NBME) examination. RESULTS: Ratings were returned and complete data were available for 203 (87.5%) of the graduates. Among all the parameters of medical school performance, the data-collection score on the clinical skills examination correlated best (.273) with performance as a first-year resident. The correlations between the residency ratings and scores on the NBME I and II were practically zero. CONCLUSION: This comparatively strong correlation between the graduates' data-collection scores and their performance ratings as first-year residents suggests that performance-based assessments using standardized patients may be at least as good as--perhaps even better than--traditional methods of evaluating medical students in predicting their performances as first-year residents. PMID- 8352877 TI - Students' psychosocial characteristics as predictors of academic performance in medical school. AB - PURPOSE: To investigate the incremental effects of selected psychosocial measures -beyond the effects of conventional admission measures--in predicting students' academic performances in medical school. METHODS: In 1989-90, 210 second-year students at Jefferson Medical College were each asked to complete 11 psychosocial questionnaires that were then used as predictors of performance measures in medical school. The students' scores on three subtests of the Medical College Admission Test (MCAT) were also used as predictors. Three composite measures of performance were used as the criterion measures: basic science examination grades, clinical examination grades, and ratings of clinical competence. A multiple regression algorithm (general linear model) was used for statistical analysis. RESULTS: The response rate was 83% (175 students). When the psychosocial measures were added to the statistical models in which the common variances of the MCAT scores were already determined, significant increments in the common variances were observed for two of the three performance measures: basic science grades and clinical examination grades. Whereas only 4% of the common variance in the ratings of clinical competence could be accounted for by the MCAT scores, 14% could be accounted for by the psychosocial measures. CONCLUSION: The "noncognitive," or psychosocial, measures increased the magnitude of the relationships between the predictive and criterion measures of the students' academic performances, beyond the magnitude attained when only the conventional admission measures were used. Therefore, psychosocial measures should be considered as significant and unique predictors of performance in medical school. PMID- 8352878 TI - Senior students' evaluations of the usefulness of the Glaxo Pathway Evaluation Program. AB - PURPOSE: To examine the influence of the Glaxo Pathway Evaluation Program on fourth-year medical students' specialty-choice decisions. METHOD: In February 1992, 274 seniors at three medical schools were asked to complete a 19-item questionnaire regarding their evaluations of the usefulness of the Pathway program in helping them to make their specialty-choice decisions. RESULTS: A total of 237 seniors responded to the survey (though not all responded to all 19 items), indicating that they found the program to be moderately useful. More than half of the students (107 of 207, 51.7%) reported that they had followed the program's decision-making model and found it moderately useful. The students' responses indicated that those components intended to facilitate self-assessment and provide information about the various specialty options were fairly well utilized, i.e., 59.9% of the students had reevaluated the Critical Factors, and 73.6% had compared their individual profiles with the Specialty Profiles, finding both exercises moderately useful. Other follow-up activities had been used variably. CONCLUSION: The students evaluated the program as being moderately useful. The authors conclude that the program is a useful, comprehensive, and reasonably objective tool. Whether students using the program achieve long-term commitment to and satisfaction in their chosen specialties remains to be determined. PMID- 8352879 TI - Internal medicine residents' perceptions of the balance between service and education in their night-call activities. AB - PURPOSE: To quantify the workload of residents on night call and to determine the residents' perceptions of the balance between service and education in their night-call activities. METHOD: Twenty-two internal medicine residents--nine first year residents and 13 senior residents (i.e., in their second, third, or fourth year)--kept logs of their night-call activities for two periods of 16 days each in 1991-92, at a 772-bed teaching hospital affiliated with Wright State University School of Medicine. The residents used the following five-point scale to rate each activity: 1, strictly service; 3, even balance; 5, strictly education. They also recorded the total times spent on various activities. Data were analyzed by using the independent and paired t-tests. RESULTS: Ninety-eight percent of the logs were returned. The first-year and senior residents did not differ significantly in times spent on logged events. Both the first-year and the senior residents perceived many night-call activities to be weighted toward education, especially those involving evaluation of acutely ill patients being considered for hospital admission (overall mean rating of 3.3). There was no striking difference between the first-year and senior residents' perceptions of the balance between service and education in their activities. CONCLUSION: The residents' perceptions of the relationship between service and education indicate that there was an even balance between the two. The educational aspects of night call duties can and should remain an integral part of residents' training. PMID- 8352880 TI - Is colony-stimulating factor-1 a key mediator of breast cancer invasion and metastasis? PMID- 8352881 TI - Novel variants of CD44 arising from alternative splicing: changes in the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells treated with hyaluronidase. AB - CD44 is a cell-surface glycoprotein postulated to play a role in a variety of biological processes, including lymphocyte homing and tumor-cell metastasis. Several isoforms of CD44 have been identified in human cells, and the genesis of some of these isoforms has been attributed to alternative splicing. In the study presented here we amplified three novel transcript variants of CD44 from human cell lines using a reverse transcriptase-polymerase chain reaction strategy. Two of the novel isoforms differed from previously described CD44 isoforms as a result of alternative splicing that occurred at previously reported splice junctions. The third novel CD44 isoform was generated from a previously unreported alternative splice junction near the 5' end of the open reading frame. Southern blot analysis of genomic DNA revealed that these novel isoforms and all of the previously described CD44 isoforms arose from alternative splicing. The capability of cells to modify their CD44 alternative splicing pattern was demonstrated in MCF-7 cells, which altered their CD44-isoform expression pattern in response to treatment with hyaluronidase. A better understanding of mechanisms regulating CD44 alternative splicing may provide insights into diverse processes, including tumor-cell metastasis and lymphocyte homing. PMID- 8352882 TI - Association of protein kinase C activation with induction of ornithine decarboxylase in murine but not human keratinocyte cultures. AB - The goal of this study was to compare the response of mouse epidermal keratinocytes (MEKs) and human epidermal keratinocytes (HEKs) to 12-O tetradecanoylphorbol-13-acetate (TPA) with respect to the activation and downregulation of protein kinase C (PKC), the expression of c-jun and c-fos, and the expression and induction of ornithine decarboxylase (ODC) activity. Keratinocytes from adult CD-1 mice and from discarded adult human skin were grown in primary culture in a high-calcium serum-free medium that supported proliferation and differentiation. Immunoblotting of freshly isolated and cultured MEKs and HEKs for isozymes of protein kinase C revealed that fresh HEKs contained PKC alpha, PKC beta, and PKC delta; no PKC gamma, PKC epsilon, or PKC zeta were detected. In fresh MEKs, PKC alpha, PKC beta, PKC delta, and PKC zeta were observed, but not PKC gamma or PKC epsilon. After 2 wk in culture, the isozyme profiles of MEKs and HEKs were similar except that PKC gamma was noticeably present in HEK cultures. Activation of partially purified total PKC by TPA was similar in freshly isolated and cultured MEKs and HEKs, indicating that the two species were similar in this regard and that 2 wk of culture did not alter this characteristic. When MEK and HEK cultures were treated with TPA for 3 h, less than 30% of the control level of PKC activity was detected, indicating that TPA-induced downregulation of PKC was similar in MEKs and HEKs. After treatment with TPA, MEK cultures produced a large induction of both c-jun and c fos mRNA by 60 min, as determined by northern blot analysis, and a large induction of ODC mRNA and enzyme activity by 6 h. TPA treatment of cultured HEKs, however, did not induce ODC activity; in fact, less activity, compared with that of control cultures, was observed. Northern blot analysis also revealed no increase in c-jun, c-fos, and ODC mRNA in HEKs. However, c-jun and c-fos mRNA and both ODC mRNA and enzyme activity were induced in HEKs fed growth factors after several days of deprivation. This suggests that the lack of ODC induction by TPA in HEKs is probably due to species differences in downstream steps in PKC signal transduction. PMID- 8352883 TI - Interleukin-1 alpha gene expression and localization of interleukin-1 alpha protein during tumor promotion. AB - Treatment of the dorsal epidermis of SENCAR mice with 12-O-tetradecanoylphorbol 13-acetate (TPA) induced a time- and dose-dependent stimulation of interleukin-1 alpha (IL-1 alpha) gene expression. Levels of IL-1 alpha mRNA were elevated as early as 15 min and peaked at 3-4 h after a single application of TPA (2 micrograms or 10 micrograms). IL-1 alpha gene expression increased in epidermal tissue isolated from SENCAR mice at 1, 3, 6, 10, 16, and 22 wk after a single treatment with 10 nmol 7,12-dimethylbenz[a]anthracene (DMBA) and subsequent twice weekly application of 2 micrograms TPA. IL-1 alpha-immunoreactive protein was specifically localized within suprabasal keratinocytes in cutaneous tissue isolated from mice treated with DMBA-TPA for 1-22 wk and in nonproliferating cells located within papilloma tissue isolated from SENCAR mice at 22 wk after initiation and promotion. Basal cells within hyperplastic epidermis did not produce IL-1 alpha-immunoreactive protein. DMBA treatment alone did not induce IL 1 alpha gene expression. Injection of IL-1 alpha-specific antibodies (50 micrograms) into SENCAR mice via the tail vein 2 h before treatment with TPA (2 micrograms or 10 micrograms) significantly (P < 0.05) inhibited the skin thickening usually observed 24 h after treatment with TPA. Autoradiography studies showed that injection of anti-IL-1 alpha antibodies inhibited incorporation of [methyl-3H]thymidine by keratinocytes within the epidermis and by cells within hair follicles. It also inhibited neutrophil infiltration into the dermis, which usually results from topical application of TPA. These data suggest that IL-1 alpha is a pivotal cytokine produced by specific subpopulations of epidermal keratinocytes and that IL-1 alpha primarily regulates the epidermal proliferative response of a distinctly separate population of keratinocytes after topical exposure of murine epidermis to TPA and secondarily modulates neutrophil migration into the dermis. Consequently, manipulation of IL-1 alpha may be a way to attenuate or abrogate the cutaneous response to TPA by altering keratinocyte proliferation, the resultant hyperplasia, and a portion of the inflammatory response characterized by dermal infiltration of neutrophils. PMID- 8352884 TI - Detection of p53 gene mutations in rat hepatocellular carcinoma cell lines by denaturing gradient gel electrophoresis. AB - Structural alterations of the p53 gene were investigated in chemically induced rat hepatocellular carcinomas (HCCs), hyperplastic hepatic nodules (HPNs), and cell lines derived from rat neoplastic and normal liver cells. The mutations were detected by GC-clamped denaturing gradient gel electrophoresis using DNA that had been amplified from p53 mRNA by the reverse transcriptase-polymerase chain reaction. This method enabled us to find single-base changes within the p53 gene without using radioisotopes. The presence of mutations was subsequently confirmed by DNA sequencing. No mutations were detected in six primary HCCs and 12 HPNs induced by the Solt and Farber regimen (Nature 236: 701-703, 1976), suggesting that p53 gene mutations do not play a major role in rat hepatic carcinogenesis. However, five of seven HCC cell lines and one of two cell lines derived from normal liver cells had the mutated p53 gene and had lost the normal p53 gene. Five cell lines had a G-->T transversion at various codons, whereas one line had a 21-base deletion in exon 5. Therefore, we conclude that p53 gene mutations may occur in vitro during establishment of the cell lines or may be derived from very small populations within the primary tumors. PMID- 8352885 TI - High variability of nitrosamine metabolism among individuals: role of cytochromes P450 2A6 and 2E1 in the dealkylation of N-nitrosodimethylamine and N nitrosodiethylamine in mice and humans. AB - We undertook this study to answer several questions regarding nitrosamine metabolism. Kinetics of nitrosamine metabolism showed the involvement of at least two enzymes in the dealkylation of N-nitrosodiethylamine (NDEA) and N nitrosodimethylamine (NDMA) in mouse liver microsomes. Coumarin inhibited both reactions competitively. On the other hand, microsomal coumarin 7-hydroxylase was inhibited by NDMA (Ki 2.7 mM) and NDEA (Ki 0.013 mM). The big difference in the Ki values suggests a higher affinity of NDEA than NDMA to Cyp2a-5 (mouse cytochrome P450coh). A specific antibody against Cyp2a-5 inhibited more of the microsomal NDEA (up to 90%) than NDMA (up to 40%) dealkylation. The converse was true with anti-Cyp2e-1 antibody. These results suggest that the primary substrate for Cyp2a-5 is NDEA and for Cyp2e-1, NDMA. Western blot analysis of human liver microsomes showed a great interindividual variation in the amounts of CYP2A6 (human cytochrome P450coh) and CYP2E1. Also, coumarin 7-hydroxylation and nitrosamine dealkylation varied greatly among individuals. A high correlation (r = 0.93, P < 0.001) was found between NDEA and coumarin metabolism. Both activities were associated with CYP2A6. On the other hand, little or no correlation was found between microsomal CYP2A6 and CYP2E1 or between CYP2E1 and NDEA dealkylation. Immunoinhibition of human microsomal NDEA metabolism by CYP2a 5 antibody varied greatly among individuals (10-90%), suggesting, as in the case of mice, that NDEA is metabolized primarily by CYP2A6, at least in some individuals. Taken together the data suggest that (1) the metabolic activation of nitrosamines in humans varies greatly among individuals; (2) different nitrosamines may partially be metabolized by different cytochrome P450 isozymes; and (3) because of similarities between nitrosamine metabolism in mice and humans, inbred strains of mice would be relevant experimental models for studying nitrosamine activation. PMID- 8352886 TI - High expression of cytochrome P450 2a-5 (coumarin 7-hydroxylase) in mouse hepatomas. AB - A high level of Cyp2a-5 was found in spontaneous and transplanted mouse hepatomas compared with normal liver. Increased expression of Cyp2a-5 was associated with an increase in coumarin 7-hydroxylation, a marker activity of Cyp2a-5, and the corresponding mRNA, suggesting that regulation of Cyp2a-5 in hepatomas is pretranslational. In contrast, the total P450 content and arylhydrocarbon hydroxylase and amidopyrene demethylase activities decreased. Pyrazole, a strong inducer of Cyp2a-5 in normal mouse livers, also increases this isozyme in hepatomas. A parallel increase in the corresponding mRNA suggests that pyrazole, like the formation of hepatomas, affects the regulation of Cyp2a-5 pretranslationally. PMID- 8352887 TI - Activation of immediate-early gene expression by peroxisome proliferators in vitro. AB - The hepatocarcinogenicity of peroxisome proliferators (PPs) in rodents has been attributed both to oxidative DNA damage resulting from excessive leakage of peroxisomal H2O2 and to increased hepatocellular replication that may be independent of peroxisome proliferation. Because of the growing association between tumor promotion and alterations in growth-regulatory signal transduction pathways, we investigated whether PPs can modulate these pathways in a mouse liver epithelial cell line, BNL-CL.2. We tested two PPs that differ markedly in rodent tumorigenicity for their ability to activate immediate-early proto oncogene expression. 4-Chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy 14643), a highly tumorigenic PP, was an exceptionally strong inducer of c-fos expression. Wy-14643 was also stronger than DEHP in stimulating c-jun expression, whereas both PPs were fairly strong inducers of jun-B and jun-D. The induction of fos and jun expression by Wy-14643 was specifically inhibited by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperizine dihydrochloride (H-7). DEHP-induced gene expression was strongly inhibited by H-7, but was also partially inhibited by an inhibitor of protein kinase A. The activation of fos and jun gene expression by PPs was independent of peroxisome proliferation since it was an immediately-early response not requiring protein synthesis and since the cell lines used in this study do not undergo peroxisome proliferation. Our r results raise the possibility that the carcinogenicity of PPs may be due, in part, to epigenetic modulation of growth-regulatory signal transduction pathways. PMID- 8352888 TI - Timing of replication of differentially transcribed genes in Syrian hamster embryo fibroblasts. AB - Syrian hamster embryo cell lines have been used as models of neoplastic progression in vitro. Changes in phenotype and biological properties have been observed in these cell lines in association with modulation of gene transcription. We explored this natural evolution of cells in culture to investigate the reported relationship between transcriptional activity and replication in early S phase. In this study we used two nontumorigenic cell lines that had either retained (supB+) or lost (supB-) the ability to suppress tumorigenicity of malignantly transformed hamster fibroblasts (BP6T). In association with the loss of suppressor gene function, supB- cells have downregulated the expression of the H19 and tropomyosin-I (TM-I) genes, which are actively transcribed in supB+ cells. Synchronous populations of supB+ and supB- cells were pulse-labeled with [3H]thymidine and bromodeoxyuridine at 1-h intervals during S phase; the replicating DNA was isolated by centrifugation in cesium chloride gradients and hybridized to 32P-labeled gene probes. No correlation was found between the timing of gene replication and the status of expression of these two genes. TM-I replicated during the first hour and H19 replicated between the second and third hours of the S phase in the expressing and nonexpressing cell lines. Immunoglobulin gene sequences, known to be late replicating in fibroblasts, replicated at the end of the S phase. These results suggest that downregulation of transcription is not always accompanied by a concomitant change in time of gene replication from early to late S phase. PMID- 8352889 TI - Heritable colorectal cancer and cancer genes: systemic expressions. AB - Epidemiological studies of heritable cancer have demonstrated that cancer predisposition is a dominant trait; these studies have also predicted the recessive outcome of the neoplastic process. Biochemical studies of dominantly heritable cancer have demonstrated the relevance of systemic effects. The systemic effects are presumably due to a dominant mutation at the "initiator locus." Collectively they define cancer initiation at the cellular level (as described in this review). Molecular biological studies have demonstrated that cancer progression and the appearance of clinical cancer occur through an accumulation of recessive mutations at critical loci. We must continue to try to define not only the inherited and acquired gene defects that initiate the neoplastic state but also the subsequent genetic alterations and biomarkers involved in tumor progression. These genetic defects are already proving useful in diagnosis and prognostication. The hope is that these biomarkers may be useful for designing specific differentiation therapy. PMID- 8352890 TI - Rare frequency of activation of the Ki-ras gene in rat colon tumors induced by heterocyclic amines: possible alternative mechanisms of human colon carcinogenesis. AB - Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed. PMID- 8352891 TI - No point mutation of Ha-ras or p53 genes expressed in preneoplastic-to-neoplastic progression as modeled in mouse JB6 cell variants. AB - Alterations of the p53 gene have been found in many human and animal tumors, and ras mutations have been seen somewhat less frequently. Loss of p53 tumor suppressor activity has been implicated in multistage tumor promotion/progression after initiation by Ha-ras or Ki-ras activation. Whether p53 or ras alterations occur during promotion of neoplastic transformation in JB6 cells has not been reported. Using a series of mouse JB6 variants representing different stages of progression toward the tumor-cell phenotype, we investigated whether mutational activation of Ha-ras and mutational inactivation and altered expression of the p53 gene occurred during progression. We report here that neither point mutations of the Ha-ras or p53 genes nor p53 structural alterations were involved in this process. Although there was no significant difference in steady-state levels of p53 mRNA, an elevated level of immunoprecipitable p53 protein was observed in a subset of transformed cells. We also report the detection of a second 2.2-kb p53 hybridizing transcript. This transcript was not translated into p53 protein and may be a nuclear precursor of the mature message. Both p53-hybridizing transcripts were downregulated by prolonged 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment (24 h) regardless of the stage of progression. We conclude from this study that in JB6 variants (1) mutational activation of Ha-ras and inactivation of p53 are unlikely to be involved in preneoplastic progression; (2) increased amounts of p53 protein may be involved in a subset of transformed cells, possibly reflecting a longer half-life, as demonstrated in other systems; and (3) late downregulation of p53 mRNA but not protein expression may be a secondary response in the TPA-mediated signal transduction pathway. PMID- 8352892 TI - Protein synthesis-dependent cytoplasmic translocation of p53 protein after serum stimulation of growth-arrested MCF-7 cells. AB - p53 protein was localized in the cytoplasm of growing and in the nucleus of growth-arrested MCF-7 cells. While the absolute amount and rate of synthesis of p53 in growing and arrested cells were nearly the same, the protein in growing cells was phosphorylated to a greater extent than in arrested cells. The abilities of the cytoplasmic and nuclear p53 proteins to bind to DNA sequences specific for p53 protein binding did not differ remarkably despite their differential phosphorylation levels. Serum-induced translocation of the p53 protein from the nucleus to the cytoplasm, as well as DNA and protein synthesis, were inhibited by cycloheximide. These results suggest that the DNA synthesis associated cytoplasmic translocation of p53 protein in response to serum stimulation depends on de novo protein synthesis and not on alteration of the protein's ability to bind to specific DNA sequences. PMID- 8352894 TI - [Review of the original texts on wujia (Cortex Acanthopanacis)]. PMID- 8352893 TI - Nucleotide sequence analysis of c-raf-1 cDNA and promoter from a radiation resistant human squamous carcinoma cell line: deletion within exon 17. AB - The c-raf-1 proto-oncogene is the cellular homologue of v-raf, the oncogene of the acutely transforming retrovirus 3611-MSV. The product of c-raf-1 (raf-1) is a 74-kDa cytoplasmic serine/threonine protein kinase. We previously reported that antisense human c-raf-1 cDNA transfection results in reduction of the endogenous c-raf-1 transcript, decreased tumor growth rate, and enhanced radiation sensitivity of SQ-20B tumor cells established from a radiation-resistant laryngeal squamous cell carcinoma. In the study reported here, we used cDNA linked polymerase chain reaction amplification and nucleotide sequencing to examine the structure of the 3233-bp SQ-20B c-raf-1 cDNA. The 812-bp c-raf-1 promoter region was analyzed by genomic DNA amplification followed by cloning and sequencing. Sequence comparison with a previously published c-raf-1 sequence indicated no structural changes within the coding region of SQ-20B c-raf-1. However, a 4-bp deletion was observed in the 3' untranslated region within exon 17. This deletion was also present in a c-raf-1 cDNA clone isolated from a SQ-20B cDNA library. While the possibility of a 3' transcriptional control mechanism cannot be ruled out, it appears that the raf-1 protein kinase may regulate the development of radioresistant malignancies via interaction with other molecules in the damage and repair-related signal transduction pathways. PMID- 8352895 TI - [Preliminary studies on medicinal plants of Corydalis in Sichuan]. AB - This paper reports the species, distribution and medical uses of Corydalis in Sichuan Province, of which 3 species e.g., Corydalis linstowiana and C. moupinensis, are found in China for the first time, 5 species C. balansae, C. trifoliolata e. g. are found in Sichuan for the first time. Medica effects of 10 species are described. PMID- 8352896 TI - [Identification of 7 snake-drugs by protein viscosity]. PMID- 8352897 TI - [Effect of reproductive materials on the yield of Pinellia ternata (Thunb.) Breit]. PMID- 8352898 TI - [Effect of different preparations of ginger on blood coagulation time in mice]. AB - The experiments indicate that the decoction, ether extraction and suspension liquid of roasted ginger and charcoal of ginger all can markedly shorten the blood coagulation time in mice, while the decoction, ether extraction of fresh ginger and dry ginger cannot. The decoction of ginger charcoal has stronger effect than roasted ginger in shortening the blood coagulation time in mice. The effect of decoction of ginger charcoal on blood coagulation time tends to increase when the dosage is increased. PMID- 8352899 TI - [Influence of processing methods on the solubility of calcium from the Mongolian medicine zhuangxi]. AB - In search of scientific basis for rationalizing the processing method of the Mongolian medicine Zhuangxi comparative tests were effected on the contents of calcium in crude and processed calcium and gypsum rubrum, and on the solubility of calcium in 0.1 mol/L HC1 from the two minerals. PMID- 8352900 TI - [Studies on longevity tea]. AB - This paper reports the preparation, physical and chemical identification and content determination of Longevity Tea. The preparation process is advanced, the content determination is simple and accurate and thus can be taken as standards for the quality control of Longevity Tea. PMID- 8352901 TI - [Effect of different preparation crafts on the content of baicalin in shuanghuanglian (SHL) injection]. AB - The content of baicalin is stable when baicalin is added quantitatively in preparation. The time of extraction of the effective components of SHL with alcohol and the concentration of alcohol have little effect on the content of baicalin. The components can be extracted once, and the content of alcohol is preferably 85%. The pH level has greater influence on the content of baicalin, and should be controlled between 7.0 to 8.0. 0.2% activated carbon is suitable in preparation. PMID- 8352902 TI - [Chemical constituents of Acanthopanax giraldii Harms var. hispidus Hoo]. PMID- 8352903 TI - [Chemical constituents of ragweed (Ambrosia artemisiifolia L.)]. AB - Three sesquiterpene lactones isolated from the aerial parts of Ambrosia artemisiifolia were identified as psilostachyin, psilostachyin B and psilostachyin C. All of them have some molluscicidal activity against Oncomelania hupensis. PMID- 8352904 TI - [Quantitative determination of liensinine in the embryo Nelumbinis (Nelumbo nucifera Gaertn.) by TLC-scanning]. AB - The content of liensinine in the green seed embryo of Nelumbo nucifera was determined by dual-wavelength TLC-scanning. The crude drug was extracted with two different method of impregnating and refluxing. The content of liensinine was determined to be 0.853% and 0.939% and the average recovery was 97.9% and 100.9% respectively. PMID- 8352905 TI - [Experimental studies on the symptom-complex mechanism of pi man zao shi of dachengqi decoction]. AB - Experiments have shown that Dachengqi Decoction can inhibit the activity of G germs which commonly grow in the intestinal tract, inactivate the endotoxin directly in vitro, reduce the amplitude of fever caused by endotoxin injected intravenously, promote the gastric secretion and gastric retaining in rats, and increase the level of glycogen in liver. It also has some other effects. All these actions contribute to the explanation on the efficacy of Dachengqi Decoction to purge off the internal heat. PMID- 8352906 TI - [Comparison between actions of shiquandabu pills and shiquandabu liquor on immunological parameters in mice]. AB - The comparison shows that both Shiquandabu pills and Shiquandabu liquor are efficacious in strengthening the immunological functions of mice. No significant difference has been found between the two forms of preparation. There exists a good dose-efficacy relationship for the pills in immunological functions. PMID- 8352907 TI - [Clinical application and research of modified wendan tang decoction]. PMID- 8352908 TI - Stromal cells in long-term cultures: keys to the elucidation of hematopoietic development? AB - Long-term bone marrow cultures mirror many aspects of in vivo mammalian hematopoiesis. Thus, these cultures have been used widely to analyze the complex interactions that regulate hematopoietic differentiation. Hematopoiesis in vivo and in vitro is dependent on stromal cells, a mixture of support cells. In the past years numerous clonal stromal cell lines derived from murine and human tissues have been isolated and characterized. The stromal cell lines have proved to be invaluable tools for the elucidation of the molecular and cellular signals that govern differentiation and self-renewal of hematopoietic cells. This review describes the salient features of arrow cultures with a focus on the isolation and characterization of stromal cell lines. We summarize how stromal cell lines have been crucial tools for the detection, isolation, and maintenance of rare pluripotent stem cells and B lineage cells. Intriguing questions about the nature of stromal cells, their requirements for growth and differentiation, and their histogenic origin remain areas for further investigation. PMID- 8352909 TI - Immunoregulation by cytokines. AB - The study of cytokine biology relevant to the in vivo (patho)physiology of the immune response is complicated by a series of features inherent to the cytokine system. The present survey focuses on the mechanisms governing the function of cytokines that may give rise to methodological and conceptual problems concerning in vivo manipulations of immunologically relevant cytokines. Special emphasis is laid on the complex interrelation between individual cytokines (cascades, synergy, anergy, pleiotropism, and redundancy), as well as on the mechanisms that guarantee a compartmentalization of cytokines, i.e., a chronological, spatial, cell-type differentiation stage, and activation-dependent restriction of their function. The in vivo effects of cytokines can be studied either by augmenting their concentration or reducing their bioavailability. The advantages of local and systemic cytokine injections, usage of transgenes, or expression as gene products encoded by recombinant viruses are discussed and contrasted with different manipulations provoking cytokine deficiencies, namely the application of cytokine antagonists, neutralizing antibodies and receptor derivates, receptor targeted cytotoxic drugs, and germ line disruption of cytokine genes. Both types of intervention are afflicted with major problems. Whereas providing an excess of cytokines in vivo, especially at the systemic level, constitutes an essentially non-physiological intervention, the induction of cytokine deficiencies will only unravel essential effects, but is incapable of elucidating the many pleiotropic cytokine effects that, by virtue of the redundancy of the system, compensate for each other. PMID- 8352910 TI - Evolution of immune reactions. AB - The history and evolutionary pathways of defense reactions among various forms of life are reconstructed. The vertebrates evolved step-by-step from their invertebrate ancestors living in the distant past. The ancestry of vertebrate defense mechanisms must be traceable to them because these functions cannot be considered separately from the common evolutionary schema. The first part of this survey is therefore devoted to the description of major defense reactions and achievements in invertebrates. Particular emphasis is given to the taxa of present-day invertebrates most likely to exhibit some relationship to the chordates and thus to show real traces of vertebrate immune patterns. The second part involves three key assemblages of deuterostomate animals--the echinoderms, the nonvertebrate chordates, and the first vertebrates because these animals are believed to have created the prerequisites for transition from the invertebrate type of defense to the vertebrate type of adaptive immunity. PMID- 8352911 TI - Diagnosis and treatment of depression in general practice. PMID- 8352912 TI - Side-effects of antidepressants. PMID- 8352913 TI - Comparisons of clinical efficacy. PMID- 8352914 TI - Suicide in depressed patients: medico-legal issues. PMID- 8352915 TI - Debits and credits in the management of depression. AB - Concern over the cost of health care is playing an increasing role in Great Britain, but evaluation of benefit is generally inadequate. This is particularly true in the case of depression, for which the cost of drugs is 1.9% of the National Health Service pharmaceutical budget. Since differences in effectiveness between antidepressant drugs are difficult to demonstrate, quality-of-life studies may help to identify outcome differences. At present, the worst outcome of depressive illness--suicide--absolves carers from further costs. An assessment is needed which takes into account both the direct and indirect costs of depression; this should include the costs of investment into improving diagnosis. Even without financial analyses, it is clear that some cases of suicide can be prevented by prescribing less toxic drugs, but research is needed to investigate whether use of these drugs also reduces the costs of overdose. PMID- 8352916 TI - The economic evaluation of antidepressant drug therapy. PMID- 8352917 TI - Cost management: the economist's viewpoint. PMID- 8352918 TI - Epilepsy and mental retardation: an overview. PMID- 8352919 TI - Epilepsy in institutionalized patients with encephalopathy: clinical aspects and nosological considerations. AB - This study was designed to correlate the prevalence of epilepsy with the severity and type of encephalopathy of 1,023 institutionalized patients and tentatively classify each according to the Proposals of the Commission on Classification and Terminology of the International League Against Epilepsy. Of this sample, 326 individuals were diagnosed with epilepsy. Sex distribution and mean age in the epilepsy and no epilepsy groups were similar, but degree of handicap was higher for those with epilepsy. Of these individuals 32.5% had a partial form. Of the 204 patients with generalized epilepsy (62.5%), 64 had a form with electroclinical characteristics of the idiopathic type; 57, a syndromic form (53 cases with a Lennox-Gastaut syndrome); and 83, a nonsyndromic form. Degree of handicap and frequency of seizures were lower in subjects with partial epilepsy and with those having electroclinical characteristics of the idiopathic type. PMID- 8352920 TI - Changes in antiepileptic drug prescribing patterns in large institutions: preliminary results of a five-year experience. AB - Routine antiepileptic prescriptions were analyzed for stable cohorts from two large, state-run, Accreditation Council-certified ICFs/MR for the time period October 1, 1987, to April 1, 1992. Results indicated marked decrease in numbers of individuals receiving (a) more than two antiepileptic drugs concurrently and (b) barbiturates. Retrospective analyses revealed that (a) over 90% of a group undergoing barbiturate taper maintained the same or improved seizure control and (b) some adults undergoing barbiturate tapers improved in target behaviors. Findings indicate the feasibility of changing antiepileptic regimens utilizing individual case evaluation and treatment and suggest the importance of considering possible psychological and behavioral disturbances associated with barbiturate therapy for adults and children. PMID- 8352921 TI - Antiepileptic drug status in adult outpatients with mental retardation. AB - Charts of 100 patients with mental retardation and epilepsy from the community were reviewed to survey use of antiepileptic drugs and examine the relation of mental retardation and seizure type to antiepileptic drug status. Sixty patients were on monotherapy and 40, on two or three antiepileptic drugs. Most subjects had generalized tonic-clonic seizures (68%), but there was a trend for those with profound retardation to have relatively more mixed seizures. Subjects on more than one antiepileptic drug were less likely to have fully controlled seizures (50%). Individuals with mixed seizures were comparatively more likely to be on more than one antiepileptic drug and have uncontrolled seizures. Implications for clinical management of epilepsy in adults with mental retardation were discussed. PMID- 8352922 TI - Control of epilepsy in a mentally retarded population: lack of correlation with IQ, neurological status, and electroencephalogram. AB - An investigation of 90 children with mental retardation and epilepsy who were seen at a developmental evaluation clinic was conducted to determine whether control of their epilepsy was related to their level of mental retardation. Their level of retardation, neurological findings, and EEGs were classified and compared with the quality of seizure control. No correlation was found between quality of control and any of these parameters. Results suggest that there is no firm relation between the level of mental retardation and control of epilepsy. It also appears that the neurological status and EEG do not affect quality of seizure control for this group. PMID- 8352923 TI - Movement of individuals with complex epilepsy from an institution into the community: seizure control and functional outcomes. AB - The successful community placement of 15 medically fragile individuals with profound mental retardation and complex epilepsy was examined. We found that simplification of anticonvulsants, early intervention for seizures, and improved staff education resulted in (a) fewer seizures, (b) decreases in emergency room visits for status seizures and drug-related side effects, and (c) increased levels of functioning as measured by activities of daily living. This program allowed for a medically fragile epileptic population to be transferred from the institution to the community. PMID- 8352924 TI - Mental retardation, mental illness, and seizure diagnosis. AB - The coexistence of epilepsy in individuals with mental retardation and mental illness is common. Little is known about whether individuals with all three conditions do significantly worse on inpatient units compared to persons with mental retardation and psychiatric disorder but without a seizure diagnosis. During 62 consecutive months, 247 individuals with mental retardation and psychiatric disorders were discharged from a university hospital. A review of discharge summaries yielded 39 individuals with a seizure diagnosis. The only difference between the groups with and without seizures was level of mental retardation. No differences existed with regard to length of stay, transfer to state hospital, psychiatric co-morbidity, or medical illness. Although it is sometimes difficult for many individuals with mental retardation to be admitted to a psychiatric hospital during exacerbations of mental illness, they should not be further stigmatized by presence of a seizure diagnosis. PMID- 8352925 TI - Temporal expression of tissue inhibitors of metalloproteinases in mouse reproductive tissues during gestation. AB - Tissue inhibitors of metalloproteinases (TIMPs) appear to play an important regulatory role in tissue remodelling and invasion by malignant cells. Since pregnancy involves morphological changes in existing maternal tissues, as well as a strictly controlled invasion by fetal trophoblasts, we have examined the temporal expression of TIMP-1, TIMP-2, and specific metalloproteinases in the mouse uterus, decidua, placenta, amnion, and ovaries throughout gestation by examining mRNA levels on northern and slot blots. Maximal levels of TIMP-1 mRNA were observed from day 6 to day 10 in the uterus, decidua, and placenta. In clear contrast to the early burst of TIMP-1 mRNA accumulation, the level of TIMP-2 mRNA increased steadily throughout gestation in the uterus, decidua, and amnion, while in the placenta it showed a sevenfold increase after day 14. In amnion, TIMP-1 was induced specifically on day 18. Interestingly, the normally high level of TIMP-1 mRNA seen in the ovaries of virgin mice was low during gestation, until day 18 and postpartum, when a sixfold increase over the levels in virgin ovary was observed. In contrast, ovarian TIMP-2 mRNA showed a marginal increase during gestation. The temporal pattern of 72 kDa gelatinase type A followed that of TIMP 2 in the decidua and ovary. Stromelysin-2 mRNA was detected at term only in ovary and decidua. Our data show that the temporal accumulation of TIMP-1 and TIMP-2 mRNA is precisely coordinated in each of the tissue compartments and is independently regulated during the in vivo remodeling of reproductive tissues in gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352926 TI - Glucose, pyruvate, and lactate concentrations in the blastocoel cavity of rat and mouse embryos. AB - The concentrations of glucose, pyruvate, and lactate have been measured in the blastocoel fluid of single rat and mouse blastocysts, using the technique of micropuncture combined with an ultramicrofluorescence assay. When cultured in the presence of 5.55 mM glucose, 11.5-12.5 mM L-lactate and 0.25-0.33 mM pyruvate, concentrations in the blastocoel fluid of mouse and rat were 2.30 and 2.75 mM glucose, 14.6 and 19.6 mM L-lactate, and 0.13 and 0.50 mM pyruvate, respectively. When cultured in the presence of 1.0 mM glucose and 1.0 mM L-lactate, concentrations in the blastocoel fluid were 0.50 and 0.59 mM glucose and 2.22 and 3.70 mM L-lactate, respectively. These results suggest that (1) the blastocyst is capable of maintaining considerable concentration gradients of substrates across the trophectoderm, (2) the microenvironment of the blastocoel is adequately supplied with energy substrates for the development of the inner cell mass, and (3) the inner cell mass is capable of developing in both high and low glucose and lactate concentrations. PMID- 8352927 TI - Transcriptional activity and nuclear ultrastructure of 8-cell bovine embryos developed by in vitro maturation and fertilization of oocytes from different growth categories of antral follicles. AB - The normalcy of nuclear differentiation in 8-cell bovine embryos derived by in vitro procedures from oocytes isolated from antral follicles of three different size categories was studied using autoradiographic localization of RNA synthesis and fine-structure nuclear morphology. In the few embryos derived from the oocytes from the small category of follicles (1-2 mm) the unlabeled nuclei prevailed. In contrast, the oocytes isolated from the more progressed follicles (medium and large size: 2-8 mm) yielded embryos with only slight, if at all detectable, differences to the picture expected in in vivo developed normal embryos. The diverging features probably concerned a slower onset of gene transcription, its consecutive pattern of localization as well as less pronounced progress of chromatin condensation and nucleolar differentiation. The assessment of these morphological changes and characteristics for individual embryos was obscured by marked differences in the status of the nuclei of particular blastomeres forming an embryo. Here the differences were seen in the fragmentation of nuclei, in the degree of chromatin condensation and in the absence of the nucleolus-associated chromatin in some of the blastomeres. It is suggested that most of the embryos from medium and large follicles have a comparable differentiation pattern of nuclear function development as embryos developing normally in vivo. PMID- 8352928 TI - Binding characteristics and immunolocalization of porcine seminal protein, PSP-I. AB - PSP-I, a 13 kDa protein purified from boar seminal plasma, was found to have about 50% amino acid sequence homology with a family of zona pellucida-binding proteins known as spermadhesins. These proteins are produced by the accessory gland(s) of the male reproductive tract and coat the spermatozoa during ejaculation. In this study, we have investigated the possible biological functions of PSP-I using a solid-phase protein binding assay and its site of synthesis using both Western blot and immunocytochemical analyses. PSP-I was found to bind a number of proteins including endo-beta-galactosidase digested ZP3, soybean trypsin inhibitor, IgA, IgG and alpha-casein, indicating that it may have multiple functions. The protein or carbohydrate structures were not critical in the binding, since polyvinyl sulfate could effectively inhibit the binding of PSP-I to these proteins. Western blot analysis using specific antiserum to PSP-I showed that the protein was present in the seminal vesicle but not in the testes, epididymis or prostate. The protein was revealed by immunocytochemical analysis in the epithelium of seminal vesicles but not in the testes or the epididymis. It is concluded that PSP-I is synthesized by the epithelium of the seminal vesicles, secreted into the semen during ejaculation, and may be involved in various reproductive functions, such as preventing premature acrosome reaction and immunosuppression. PMID- 8352929 TI - ZNC(C)PR affects developmental changes of P46 phosphorylation in rat hippocampus. AB - Protein phosphorylation has been suggested to be correlated with brain development and with the molecular mechanism of behavioral effects of neuropeptides. The present study reports in vitro endogenous phosphorylation of P46, a membrane-associated protein that is changed during development of the rat hippocampus. This study indicated that the degree of endogenous phosphorylation may be correlated with the establishment of synaptic connections. Interestingly, P46 was proved to be identical to a well-known growth-associated protein B-50/GAP 43 in its identical apparent molecular weight, isoelectric point, phosphorylation dependence, and the cross immunoreaction of monoclonal anti-B-50/GAP-43 antibody and P46. Moreover, neonatal administration of neuropeptide ZNC(C)PR could facilitate the developmental progress of P46 endogenous phosphorylation. It is suggested that the changes in P46 phosphorylation could be involved in the cellular mechanism of ZNC(C)PR behavioral effects on learning. PMID- 8352930 TI - Changes in ovarian follicles and in vitro sex hormone release in the lizard Podarcis sicula sicula. AB - An in vitro superfusion method was used to test sex hormone release from different kinds of ovarian follicle (growing follicles, postovulatory follicles, and atretic follicles) in the lizard Podarcis sicula sicula. Sex hormone output changes with the stage of follicle evolution and sexual cycle. Previtellogenetic follicles prevail in early-spring quiescent ovaries and secrete mainly progesterone, which is probably utilized at that phase to delay ovarian resumption. In the acute ovary, progesterone output from previtellogenetic follicles decreases, whereas vitellogenetic follicles produce a significant amount of 17 beta-estradiol, which is necessary for sustaining vitellogenin synthesis by the liver and oviduct growth. As follicles become ripe, progesterone production is resumed, and it increases in young postovulatory follicles. This is in line with the functions assigned to the hormone at that phase of the sexual cycle, i.e., the induction of oocyte maturation and the regulation of egg retention in the oviduct. Postovulatory follicles can also synthetize 17 beta estradiol. After oviposition, this hormone, which is secreted by the old postovulatory follicles, can reinitiate vitellogenin synthesis, allowing the development of a new oocyte set. Our data confirm that active, although ephemeral, corpora lutea are also formed in oviparous species. A limited contribution to ovarian sex steroid production derives also from atretic follicles, at least at the early stages of the breeding cycle. PMID- 8352931 TI - Immunoelectron microscope localization of snRNP, hnRNP, and ribosomal proteins in mouse spermatogenesis. AB - We have studied the ultrastructural distribution of heterogeneous nuclear ribonucleoproteins (hnRNPs), small nuclear ribonucleoproteins (snRNPs), and ribosomal proteins during mouse spermatogenesis and spermiogenesis by means of specific antibodies and immunocytochemistry. All the above components were detectable from primary spermatocytes until the spermatid elongation phase, when the RNA synthetic activity is known to cease. Ribosomal protein (P1/P2 and L7) labeling disappeared as early as during the acrosome phase, and nucleoli were no longer labeled even during the cap phase. The nucleoplasmic structures labeled with the different anti-nucleoplasmic RNP immunoprobes corresponded, until the acrosome phase, to those previously observed as targets of the same antibodies in the nucleoplasm of somatic cell nuclei. Clusters of interchromatin granules of spermatocyte and early spermatid nuclei exhibit some labeling for hnRNP when compared with nuclei of Sertoli cells or previously analyzed liver or tissue culture cells, where these structural constituents usually remain weakly labeled or unlabeled. In spermatids in step 10, another type of nuclear granule, resembling perichromatin granules, but occurring in aggregates, can be observed. These structural constituents were labeled with antibodies recognizing nucleoplasmic snRNP antigens and therefore suggesting a non-nucleolar origin of these granules. Finally, we have observed nucleoplasmic areas of fibrogranular material, occurring only in primary spermatocytes. These components were labeled with anti-ribosomal protein antibodies but did not contain either hnRNPs or snRNPs. PMID- 8352932 TI - Spermatid nucleus of Megaselia scalaris Loew (Insecta, Diptera, Phoridae): a study using anti-histone antibodies, scanning electron microscopy, and a centromere-specific oligonucleotide. AB - The structure of elongated spermatid nuclei was examined in the fly Megaselia scalaris using indirect immunofluorescence with anti-histone antibodies, scanning electron microscopy, and in situ hybridization with a centromere-specific oligonucleotide. The immunofluorescence experiments showed that, in keeping with the situation in most animals, histones are hyperacetylated prior to their displacement from the nucleus in the course of spermiogenesis. Scanning electron microscopy revealed that grooves run parallel to the long axis of the spermatid nuclei. The chromatin is segmented into blocks lateral to the grooves. This finding most probably indicates that the chromatin is not yet maximally condensed at this stage. The retarded chromatin condensation may be correlated with the export of somatic histones from the nucleus. The location of the centromeres could not be identified using scanning electron microscopy, but in situ hybridization showed that a centromere-specific oligonucleotide mapped to the central or close to the central areas within the spermatid nucleus. Possibly, the chromosomes are extended and arranged parallel to the long axis of the spermatid nucleus. PMID- 8352933 TI - Lysophosphatidylcholine disrupts the acrosome of tammar wallaby (Macropus eugenii) spermatozoa. AB - The acrosomal status of wallaby spermatozoa was evaluated by light and electron microscopy after incubation in 1-100 microM lysophosphatidylcholine (LPC) for up to 120 min. Treatment with 1 and 10 microM LPC for 120 min did not lead to acrosomal loss, or detectable alteration to the acrosome, as detected by Bryan's staining and light microscopy. Incubation with 25 microM LPC had little effect on acrosomal loss, however statistically significant changes (P < 0.05) in the acrosomal matrix (altered) were detected after 10-min incubation by light microscopy. Around 50% of acrosomes were altered after 20-min incubation in 50 microM LPC (P < 0.001), and 40% of spermatozoa had lost their acrosome after 60 min incubation (P < 0.001). Treatment with 75 and 100 microM LPC led to rapid acrosomal loss from around 50% of spermatozoa within 10 min (P < 0.001), and by 60 min acrosomal loss was 70-80%. LPC, like the diacylglycerol DiC8 (1,2 dioctanoyl-sn-glycerol), is thus an effective agent to induce loss of the relatively stable wallaby sperm acrosome, and it also induces changes within the acrosomal matrix. Ultrastructure of the LPC-treated spermatozoa revealed that the plasma membrane and the acrosomal membranes were disrupted in a manner similar to that seen after detergent treatment (Triton X-100). There was no evidence of point fusion between the plasma membrane overlying the acrosome and the outer acrosomal membrane. The plasma membrane was the first structure to disappear from the spermatozoa. The acrosomal membranes and matrix showed increasing disruption with time and LPC concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352934 TI - Biotinylation of proteins on the surface of zona-free mouse oocytes. AB - In this study, we have labelled proteins on the surface of unfertilized, zona free mouse oocytes using a nonisotopic biotinylation procedure. The zona pellucida was weakened by brief incubation in chymotrypsin and removed by mechanical pipetting through a narrow-bore glass pipette. Surface proteins were labelled using sulfo-NHS-biotin (sulfosuccinimidobiotin), a water-soluble, membrane-impermeable biotinylation reagent. The distribution of biotinylated proteins on the oocyte surface was assessed by fluorescence microscopy using streptavidin-FITC. Bright fluorescence was noted on the surface of the oocyte, except in a circular region overlying the meiotic spindle where the fluorescence was weak or absent. The intensity of fluorescence was markedly reduced by incubation of biotinylated oocytes in trypsin (1 mg/ml) or chymotrypsin (2 mg/ml), and in vitro fertilization experiments showed that biotinylation did not compromise the fertilizability of the oocytes. The biotinylated proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by Western blotting using streptavidin-HRP and enhanced chemiluminescence (ECL) detection. The most prominent biotinylated proteins were of M(r) 82 and 69 kD, but other major proteins of M(r) 93, 78, 61, 52, 49, 40, 28, and 22 kD were detected, as well as 14 minor proteins of M(r) 18-100 kD. The major bands could be detected in fewer than 50 oocytes. This biotinylation procedure is fast, versatile and sensitive, and it is therefore an excellent tool for studying proteins exposed on the surface of mammalian oocytes and embryos. PMID- 8352935 TI - Biochemical characterization and epididymal localization of the maturation dependent ram sperm surface antigen ESA152. AB - We examine here the biochemical properties and epididymal localization of a maturation dependent ram sperm surface antigen. A monoclonal antibody, ESA152, identifies an antigen that is present on the surface of ejaculated sperm, but is absent from testicular sperm. Crosslinking of the ESA152 antigen with bivalent antibodies induces the acrosome reaction, redistributing the antigen into the anterior region of the sperm head where it associates with the fusion product of the plasma membrane and the outer acrosomal membrane. The ESA152 antigen appears as a polypeptide of 18 kDa on immunoblots of SDS-polyacrylamide gels. The ESA152 epitope includes the sialic acid termini of N-linked oligosaccharides, as shown by its sensitivity to neuraminidase and endoglycosidase F. The ESA152 antigen is a highly hydrophobic integral membrane protein that resists aqueous extraction, partitions into the detergent phase of Triton-X-114, and solubilizes in chloroform-methanol mixtures. The anchoring of ESA152 is unaffected by phosphtidylinositol specific phospholipase C. The antigen is absent from extracts of caput and corpus epididymidis but appears abruptly in the first segment of the cauda. Immunofluorescence reveals that the ESA152 epitope first appears in clusters of cells in the luminal epithelium of the proximal cauda, prior to or concurrent with its appearance on sperm. PMID- 8352936 TI - Analysis of lipid peroxidation mechanisms in human spermatozoa. AB - The mechanisms by which ferrous ion promoters induce malondialdehyde generation by human spermatozoa have been investigated in order to provide a rational basis for the quantification and interpretation of lipid peroxidation assays. Incubation of human spermatozoa with a ferrous ion promoter in the presence of thiobarbituric acid (TBA) led to the generation of the bone fide malondialdehyde TBA adduct. The importance of iron in the stimulation of lipid peroxidation was emphasized by the ability of Desferal and EDTA to suppress malondialdehyde generation. Paradoxically, when the concentration of EDTA relative to iron was equimolar or greater, the suppression of malondialdehyde formation was accompanied by the generation of hydroxyl radicals. These results suggested that the addition of promoter did not effect the first-chain initiation of lipid peroxidation but favored an alternative mechanism involving the catalytic decomposition of pre-existing lipid peroxides. This conclusion was reinforced by the inability of reagents that would limit the formation (superoxide dismutase and/or catalase) or availability (mannitol, formate) of hydroxyl radicals, to influence malondialdehyde generation. While hydroxyl radicals were not directly involved in Fe(2+)-promoted malondialdehyde generation, the existence of significant correlations between reactive oxygen species production and the outcome of the TBA assay, suggested that Fenton chemistry might be important in the initiation of peroxidative damage. It is proposed that the impeded propagation of peroxidation initiated by Fenton or Haber Weiss reactions would lead to the accumulation of lipid peroxides in the spermatozoa and it is these peroxides that are induced to decompose during the Fe(2+)-promoted TBA assay, stimulating a lipoperoxidative chain reaction and malondialdehyde formation. PMID- 8352937 TI - Multiple effects of seminal plasma on the acrosome reaction of human sperm. AB - Mammalian sperm do not respond to inducers of the acrosome reaction immediately after ejaculation. They become responsive after they are removed from seminal plasma and incubated in an appropriate medium. We tested the effects of seminal plasma on the development of acrosomal responsiveness. Washed human sperm incubated 24 hr in vitro with 10% (v/v) seminal plasma did not complete an acrosome reaction when exposed to human follicular fluid, progesterone, or ionomycin. Seminal plasma did not reduce sperm viability or motility. Electron microscopy of sperm incubated 24 hr with 5% seminal plasma and then treated with progesterone revealed no sign of membrane fusion or other changes that are associated with the acrosome reaction. During a 12-hr incubation, seminal plasma was 50% effective at inhibiting the acrosomal response to progesterone when diluted 821 +/- 112 fold (mean +/- SD, n = 3). Sperm that were incubated with seminal plasma for 24 hr and then washed free of the seminal plasma became acrosomally responsive over the following 24 hr, at a rate similar to that of sperm not incubated with seminal plasma in vitro. When sperm were incubated 6 hr without seminal plasma and then seminal plasma was added, the sperm population transiently became more responsive to progesterone, and then became unresponsive. During incubation in vitro, the ability of sperm to have an augmented response to a mixture of seminal plasma plus progesterone developed slightly earlier and more rapidly than ability to respond to progesterone alone. When sperm were incubated 24 hr without seminal plasma, a few acrosome reacted in response to the addition of seminal plasma alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352938 TI - Sperm:egg ratios and putative molecular signals to modulate gamete interactions in polytocous mammals. AB - Reasoning from the premises that 1) the sperm:egg ratio at the time of activation of the secondary oocyte in mammals is close to unity under conditions of spontaneous mating, 2) a majority of eggs within the cumulus oophorus of a polytocous species is fertilized in a reasonably short interval of time, and 3) spermatozoa would find it difficult to reverse their approach to the zona pellucida, it is proposed that molecular gradients exist to divert spermatozoa penetrating the cumulus mass away from eggs already activated and towards eggs as yet unfertilized. Possible sources of such molecular cues are considered, as is the event that triggers their release. PMID- 8352939 TI - Tumor suppressor genes. PMID- 8352940 TI - Preferential expression in mushroom bodies of the catalytic subunit of protein kinase A and its role in learning and memory. AB - Involvement of the cAMP cascade in Drosophila learning and memory is suggested by the aberrant behavioral phenotypes of the mutants dunce (cAMP phosphodiesterase) and rutabaga (adenylyl cyclase). Line DCO581, isolated via an enhancer detector screen for genes preferentially expressed in the mushroom bodies, contains a transposon in the first exon of the catalytic subunit gene (DCO) of protein kinase A (PKA). RNA in situ hybridization and immunohistochemistry show that DCO is preferentially expressed in the mushroom bodies. The DCO581 insertion and an independently isolated hypomorphic allele (DCOB10) each produce homozygous lethality and a 40% decrease in PKA activity in heterozygotes. This decrease has mild effects on learning but no effect on memory. However, the 80% reduction in activity obtained by constructing heteroallelic yet viable DCO581/DCOB10 animals results in a dramatic learning and memory deficit. These results suggest that PKA plays a crucial role in the cAMP cascade in mushroom bodies to mediate learning and memory processes. PMID- 8352941 TI - Navigational errors made by growth cones without filopodia in the embryonic Xenopus brain. AB - We have developed an exposed brain preparation for observing growth cone pathfinding behavior while performing in vivo pharmacological manipulations, and we used it to test whether Xenopus retinal growth cones need filopodia to navigate. Time-lapse video observation showed that cytochalasin B acted quickly and reversibly when applied; cytochalasin B-treated growth cones lacked filopodia, but had active lamellipodia and continued to advance slowly. Whereas normal retinotectal axons visualized with horseradish peroxidase turn caudally in the mid-diencephalon to reach the tectum, cytochalasin B-treated axons grew past the normal turning point and, instead, continued straight within the diencephalon. In dose-response experiments, pathfinding became abnormal in the same concentration range in which filopodia disappeared. These results suggest that filopodia are necessary for retinal growth cones to respond to guidance signals in the diencephalon. PMID- 8352942 TI - S4 mutations alter the single-channel gating kinetics of Shaker K+ channels. AB - The S4 sequence comprises at least part of the voltage sensor in Shaker K+ channels. Two site-directed mutations in the Shaker S4 sequence, R368Q and R377K, which decrease the voltage dependence of the whole-cell current, alter voltage dependent gating at the single-channel level. Compared with the wild-type channel, they increase the latency to first opening, destabilize the open state, and alter the equilibria of voltage-dependent transitions, so that some of the charge movement occurs after the first opening. Whether these changes reflect a new mechanism of activation is a key question. Although the mutations alter the kinetics of many steps in the gating process, we conclude that the mutant channels are likely to activate using the same fundamental mechanism as wild-type channels. PMID- 8352943 TI - Gating currents from a nonconducting mutant reveal open-closed conformations in Shaker K+ channels. AB - In voltage-dependent ion channels, a voltage sensor region is responsible for channel activation and an aqueous pore is responsible for ion conduction. These two processes have been traditionally considered to be independent. We describe here a mutation in the putative pore region (W434F) that completely abolishes ion conduction without affecting the gating charge of the channel. Gating currents in the nonconductive mutant were found to be identical in their kinetic and steady state properties to those in conductive channels. Gating current measurements could be performed without subtracting pulses and in the presence of normal physiological solutions. Application of internal tetraethylammonium (an open channel blocker) induced Off charge immobilization for large depolarizations, suggesting that the internal tetraethylammonium-binding site becomes available upon depolarization. We concluded that for this mutant, although the conduction pathway is not functional, the channel can still undergo the closed-open conformation in response to voltage changes. PMID- 8352944 TI - Dexamethasone rapidly induces Kv1.5 K+ channel gene transcription and expression in clonal pituitary cells. AB - Glucocorticoids specifically increase Kv1.5 K+ channel mRNA in normal and clonal (GH3) rat pituitary cells. Here, we demonstrate that dexamethasone, a glucocorticoid agonist, rapidly induces Kv1.5 gene transcription, but does not affect Kv1.5 mRNA turnover (t1/2 approximately 0.5 hr) in GH3 cells. Immunoblots indicate that the steroid also increases the expression of the 76 kd Kv1.5 protein approximately 3-fold within 12 hr without altering its half-life (t1/2 approximately 4 hr). In contrast, Kv1.4 protein expression is unaffected. Finally, we find that the induction of Kv1.5 protein is associated with an increase in a noninactivating component of the voltage-gated K+ current. Our results indicate that hormones and neurotransmitters may act within hours to regulate excitability by controlling K+ channel gene expression. PMID- 8352945 TI - Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. AB - Prostaglandins play important and diverse roles in the CNS. The first step in prostaglandin synthesis involves enzymatic oxidation of arachidonic acid, which is catalyzed by prostaglandin H(PGH) synthase, also referred to as cyclooxygenase. We have cloned an inducible form of this enzyme from rat brain that is nearly identical to a murine, mitogen-inducible cyclooxygenase identified from fibroblasts. Our studies indicate that this gene, here termed COX-2, is expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus. Neuronal expression is rapidly and transiently induced by seizures or NMDA-dependent synaptic activity. No expression is detected in glia or vascular endothelial cells. Basal expression of COX-2 appears to be regulated by natural synaptic activity in the developing and adult brain. Both basal and induced expression of COX-2 are inhibited by glucocorticoids, consistent with COX-2 regulation in peripheral tissues. Our studies indicate that COX-2 expression may be important in regulating prostaglandin signaling in brain. The marked inducibility in neurons by synaptic stimuli suggests a role in activity-dependent plasticity. PMID- 8352946 TI - A novel receptor-type protein tyrosine phosphatase is expressed during neurogenesis in the olfactory neuroepithelium. AB - Tyrosine phosphorylation plays a central role in the control of neuronal cell development and function. Yet, few neuronal protein tyrosine phosphatases (PTPs) have been identified. We examined rat olfactory neuroepithelium for expression of novel PTPs potentially important in neuronal development and regeneration. Using the polymerase chain reaction with degenerate DNA oligomers directed to the conserved tyrosine phosphatase domain, we identified 6 novel tyrosine phosphatases. One of these, PTP NE-3, is a receptor-type PTP expressed selectively in both rat brain and olfactory neuroepithelium. In the olfactory neuroepithelium, PTP NE-3 expression is restricted to neurons and describes a novel pattern of expression with a high level in the immature neurons and a lower level in mature olfactory sensory neurons. PMID- 8352947 TI - In vivo recovery of repeatedly strained rat skin after systemic treatment with desmotropic drugs. AB - The mechanical behavior of rat skin during repeated strain in vivo and the restoration process thereafter were studied following 10 days' treatment with desmotropic drugs (300 mg/kg p.o. D-penicillamine or 10 mg/kg s.c. prednisolone acetate). Repeated (30 times) elongations of up to 40% were performed under anesthesia both longitudinally and perpendicularly to the body axis. Evaluation of this first run of 30 cycles showed stress values as well as the moduli of elasticity to be decreased after D-penicillamine, whereas they were greatly increased after prednisolone acetate treatment. The decay of stress values during repeated strain revealed similar effects of treatment. In the second part of the experiment, the restoration process was evaluated by a second run of 30 cycles after 1, 6 and 16 h. In the late phases of recovery, an even better restitution ad integrum was found in treated animals. Overall, in contrast to other biomechanical parameters, the restoration process is barely influenced by treatment with desmotropic compounds. PMID- 8352948 TI - How does sodium lauryl sulfate alter the skin barrier function in man? A multiparametric approach. AB - The effects of topically applied sodium lauryl sulfate were studied in vivo, in man, through noninvasive methods and compared with those obtained in vitro, using human stratum corneum as a model. The results show that the very marked increase of transepidermal water loss obtained in vivo cannot be related to any removal of epidermal lipids. The most likely explanation of our findings lies in the hyperhydration of stratum corneum consecutive to the inflammation process and a possible disorganization of the lipid bilayers. PMID- 8352949 TI - Penetration of Sandimmune (cyclosporin A) in rat skin in vitro. Effects of penetration enhancers and solvents. AB - The effect of various fatty acids or alcohols on the penetration rates and skin concentrations of cyclosporin A (Sandimmune; CyA) was evaluated in an in vitro model using skin of hairless rats. The influence of chain length, number and position of double bonds and branching of the carbon chain of the enhancer were investigated. In addition the penetration dependency of CyA on the concentration of both enhancer and CyA was studied. CyA was quantitated by high-performance liquid chromatography. The penetration rates of CyA through rat skin decreased with increasing number of double bonds of the enhancer and decreasing CyA concentrations in the donor solution, and increased with increasing chain length of the enhancer. Enhancers increase penetration rates by a factor of up to 20-90 in alcoholic vs. maximally 5-fold in oily compositions. Enhancers increase skin concentrations of CyA by a factor of up to 10-25 in alcoholic and about 4-20 in oily compositions. PMID- 8352950 TI - Glucocorticoid effect on hair growth initiation: a reconsideration. AB - It has been demonstrated by various workers in the past that glucocorticosteroids block hair growth. Using the mouse model for studying hair growth induction we reexamined the effect of topically applied steroids on hair growth to establish at what stage the steroid block acts. In accord with studies by others, we found that these steroids block hair growth at the point of anagen initiation, but that once the steroid applications are stopped, hair growth starts. Since steroid withdrawal alone did not induce hair growth, it is clear that these steroids do not block, either spontaneous or manipulated, hair growth induction, but they do block, the apparent next step, i.e., hair formation. Moreover, since hair growth could be induced even while the animals were being treated with the steroid, the induction step appears independent of the steroid block. These studies and those of others lead us to conclude that these steroids block the expression of hair forming genes, but do not interfere with the signal(s) that initiates those genes. This system appears to be ideal for identifying the signals (perhaps, genes) responsible for initiating hair growth. PMID- 8352951 TI - Computerized microassay of keratinocyte cell-plastic attachment and proliferation for assessing net stimulatory, inhibitory and toxic effects of compounds on nonimmortalized cell lines. AB - Testing of pharmacological agents that affect growth of epidermal keratinocytes (EK) requires a standardized assay. We have developed an assay measuring net effects of stimulatory (e.g. growth factors), inhibitory (e.g. methotrexate) or toxic (e.g. Triton X-100) compounds. The amount of crystal violet staining viable EK attached to the wells of standard 96-well microplates is measured in situ using an ELISA plate reader. Optical density readings are directly converted into cell counts by computer software. Counts obtained by this method strongly correlate with the results obtained using the [3H]thymidine uptake assay and direct cell counts. The assay standardizes measurements of nonimmortalized EK lines with different innate proliferative properties and allows accurate quantitation of EK numbers in the range of 2,500-500,000 EK/well. PMID- 8352952 TI - In vivo evaluation of the penetration of topically applied drugs into human skin by spectroscopic methods. AB - Spectroscopic techniques are reported on which allow to study in vivo the penetration behaviour of topically applied light-absorbing drugs into human skin. Remittance spectroscopy, a purely optical method, provides a good tool in both, skin adaptation by use of a remote viewing head coupled to the spectrometer via optical fibres, and adequate sensitivity for the detection of small amounts of the applied drugs. The measuring depth in the skin is determined by the wavelength-dependent optical penetration depth, which itself depends on light absorption and light scattering. In the UV-spectral region the optical penetration depth is of the order of the thickness of the stratum corneum (UV-A) or of only a superficial part of it (UV-B, UV-C). Fluorescence spectroscopy, another optical method, offers two kinds of drug detection, a direct one in case of self-fluorescent drugs or an indirect one being based on the light absorption of the drug, which may give rise to a screening of the self-fluorescence of the skin itself or of an applied marker. The measuring depth is comparable to that achieved with remittance spectroscopy. A third method is photothermal spectroscopy which is determined by thermal properties of the skin in addition to optical properties. Photothermal spectroscopy is unique in that it allows depth profiles of drug concentration to be measured non-invasively, as the photothermal measuring depth can be changed by varying the modulation frequency of the intensity-modulated incident light. Results of measurements demonstrating the potentials of these spectroscopic methods are presented. PMID- 8352953 TI - Assessment of topical corticosteroid activity on experimentally induced contact dermatitis: echographic evaluation with binary transformation and image analysis. AB - A new echographic evaluation method employing a B scanner and a dedicated software (Dermavision 2D, Cortex Technology, Hadsund, Denmark) was used in assessing the potency of three different corticosteroids. Experimental lesions were induced by patch tests with nickel sulfate 5% in petrolatum in 10 sensitized subjects and treated with two medications of different steroids (clobetasol propionate, fluocinolone acetonide or clobetasone butyrate) performed 16 and 40 h after the application of the nickel patch tests. Clinical and echographic evaluations were carried out at the beginning of the experiment and 64 h after the induction of the reactions. After obtaining echographic images, these were processed by software, enabling the selection of amplitudes of interest, the highlighting of parts of images and their assessment by a value corresponding to the number of pixels (picture elements). For evaluations a low reflecting band was chosen, marking edema and inflammatory infiltration. At positive patch test sites we observed a progressive increase in the number of low reflecting pixels, in accordance with the intensity of the reaction. Therapeutic response was assessed as the difference between values of treated and untreated test sites. The rank order of the efficacy of test substances as determined echographically was identical to the rank order generally accepted for these steroids. This evaluation method of topical corticosteroid activity could be usefully employed besides traditional evaluation methods. PMID- 8352954 TI - Strength and viscoelastic properties of anisotropic rat skin after treatment with desmotropic drugs. AB - Male Sprague-Dawley rats were treated 10 times either with 2 or 10 mg/kg s.c. prednisolone acetate or with 300 or 1,000 mg/kg p.o. D-penicillamine or with 100 or 300 mg/kg p.o. aminoacetonitrile bisulfate. Samples of dorsal skin were tested either longitudinally or perpendicularly to the body axis. Relaxation and hysteresis experiments were performed at different degrees of elongation. Finally, ultimate values were measured. In all groups, ultimate strain was much higher perpendicularly than longitudinally to the body axis. A dose-dependent increase of all parameters indicating strength or elasticity was found after prednisolone acetate treatment, whereas the indicators of viscosity showed a decrease. D-Penicillamine treatment decreased all parameters of strength and elasticity and increased viscosity and plasticity. Aminoacetonitrile bisulfate induced biphasic changes: after high-dose treatments strength and elasticity were increased and viscosity decreased. The results are discussed in view of changes of biochemical composition and cross-linking of collagen. PMID- 8352955 TI - Nuclear membrane dynamics. AB - Our understanding of nuclear membrane trafficking and protein targeting has increased significantly, due to newly developed assays and tools. We present a conceptual framework for thinking about protein targeting to the inner nuclear membrane, and discuss nuclear envelope assembly in terms of vesicle binding to chromatin, vesicle fusion, structural attachments to the inner membrane, and the mitotic regulation of these attachments. PMID- 8352956 TI - Lamin dynamics. AB - Nuclear lamins form a highly insoluble structure, the nuclear lamina, which is associated with the nuclear envelope. Recent results suggest, however, that the lamins are more dynamic than originally thought. They accumulate in nucleoplasmic foci in the G1 stage of the cell cycle and later appear mainly in the peripheral lamina. Some of the lamin foci are closely associated with heterochromatin. Furthermore, the various lamin types assemble into the lamina polymer independently of each other. Both the assembly and disassembly of the lamins, as well as the interaction of the lamins with other nuclear structures such as the nuclear membrane, may be mediated by phosphorylation and dephosphorylation. PMID- 8352957 TI - Chromosome structure inside the nucleus. AB - Recent in situ three-dimensional structural studies have provided a new model for the 30 nm chromatin fiber. In addition, research during the past year has revealed some of the molecular complexity of non-histone chromosomal proteins. Still to come is the unification of molecular insights with chromosomal architecture. PMID- 8352958 TI - Role of chromatin structure in the regulation of transcription by RNA polymerase II. AB - Recent studies on chromatin have concentrated on the relationship between its structure and gene activity. This topic, which addresses the fundamental mechanisms by which genes are expressed, has become a controversial issue, and the present data support the hypothesis that the structure of chromatin is an important component of transcriptional regulation. Notwithstanding, the complexity of this problem suggests that the current models are probably only a rough approximation of the truth. PMID- 8352959 TI - DNA repair. AB - Multiple DNA repair processes are required to maintain the integrity of the cellular genome. Recent advances, including elucidation of three-dimensional structures of DNA repair enzymes, and the cloning and characterization of DNA repair genes implicated in human inherited disease, have given new insights into the surprising complexity of cellular responses to DNA damage. PMID- 8352960 TI - Origins of DNA replication that function in eukaryotic cells. AB - This past year has seen a significant increase in our understanding of eukaryotic origins of replication, of the proteins that identify these origins, of DNA sequences that promote their unwinding, and of transcription factors that stimulate origin activity. DNA replication begins at specific sites in both simple and complex genomes, but origins in complex genomes may include nuclear structure as well as DNA sequence. PMID- 8352961 TI - Nuclear organization of pre-mRNA processing. AB - Recent studies have suggested that small nuclear ribonucleoprotein particles (snRNPs), non-snRNP splicing factors, and several heterogeneous nuclear RNP proteins change their organization within the cell in response to transcriptional activity. Several of the RNA substrates with which these factors interact have been shown to localize in tracks that are associated with regions in which splicing factors are concentrated (nuclear speckles). It is now thought that pre mRNA splicing may occur within these tracks. PMID- 8352962 TI - The role of small nuclear RNAs in RNA splicing. AB - Recent genetic and biochemical experiments have revealed an intimate and dynamic role for small nuclear RNAs (snRNAs) in multiple steps of RNA-splicing reactions. Both snRNA-substrate and snRNA-snRNA interactions are involved. These interactions concern not only splice site and branch point definition, but also the catalytic reactions of the first and second steps of splicing. Studies reveal a striking conservation between snRNA interactions and interactions found in RNAs encoded by genes with group II self-splicing introns. PMID- 8352963 TI - Regulation of gene expression by light. AB - The past year has seen significant advances in the biochemical, genetic and molecular dissection of the light signal transduction and developmental pathways that lead to photoregulated gene expression in higher plants. A major part of recent research has focused on the assignment of biological functions to the various photoreceptors, the genetic dissection of the photoreceptor action pathways, and the identification of the cis-acting sequences and trans-acting factors that regulate the downstream light-regulated genes. PMID- 8352964 TI - Tat and the HIV-1 promoter. AB - The HIV-1 Tat protein enhances the formation of productive RNA polymerase II elongation complexes, potentially acting through a positive-acting, DRB-sensitive elongation factor. Tat is usually recruited to the HIV-1 promoter through the Tat trans-activation response element RNA stem-loop structure; however, recent data suggest that in certain cell types it can be directed instead through upstream enhancer elements. New studies also reveal that the response element overlaps a novel motif that promotes the assembly of abortive elongation complexes in the absence of Tat. PMID- 8352965 TI - Regulation of RNA polymerase II transcription. AB - Transcription initiation plays a central role in the regulation of gene expression. Exciting developments in the last year have furthered our understanding of the interactions between general transcription factors and how these factors respond to modulators of transcription. PMID- 8352966 TI - Regulation of the NF-kappa B/rel transcription factor and I kappa B inhibitor system. AB - The interplay between proteins of the NF-kappa B/rel and I kappa B families is a tightly regulated process that ensures appropriate responses to specific environmental and developmental signals. Various mechanisms are utilized in regulating NF-kappa B/rel and I kappa B activities, some unique to this transcription factor system. All of these regulatory strategies converge towards one purpose, namely the controlled nuclear translocation of activated NF-kappa B/rel protein complexes. The variety of rel-related and ankyrin repeat containing subunits makes regulation of this system both rich and complicated. PMID- 8352967 TI - POU-domain proteins: structure and function of developmental regulators. AB - POU-domain proteins are a group of developmental regulators found in organisms as distant as worm and man. The sequence conservation of the POU-domain has allowed the characterization of increasing numbers of proteins containing the domain, many of which act to control the generation and maintenance of differentiated cell phenotypes in organs as diverse as skin and brain. Analysis of the means by which POU-domain proteins regulate transcription has led to a further understanding of how this group initiates specific developmental programs. PMID- 8352968 TI - Steroid and related receptors. AB - Steroid hormone receptors stimulate gene transcription by binding to DNA as homodimers, whereas many other members of the nuclear receptor family appear to function as heterodimers or as monomers. This is important for target gene recognition and, given that many of the receptors are expressed in multiple forms, generates many combinations of ligand-dependent transcription factors that regulate the expression of different genes in diverse pathways. PMID- 8352969 TI - Transcriptional cascades in Drosophila. AB - Genetics and molecular analyses have combined to yield insights into a functional cascade of transcription factors necessary to establish the molecular blueprint of the Drosophila body pattern in response to positional information in the egg. Recent progress in this field raises exciting questions regarding the molecular mechanisms involved, and their conservation in biological pattern-forming processes. PMID- 8352970 TI - Yeast transcription factors. AB - Studies of yeast transcription factors have contributed greatly to understanding basic molecular mechanisms of eukaryotic gene regulation, largely due to powerful genetic approaches that are unavailable in other organisms. The broad outlines of these mechanisms are fairly well understood, and there is an increasing number of examples where detailed information is available. PMID- 8352971 TI - Nucleus and gene expression. PMID- 8352972 TI - [The evaluation of cognitive deterioration in transient ischemic attacks]. AB - We compared the degree of dementia in a group of 41 patients who, four years previously, had presented a first TIA with that of 31 healthy controls of similar age. For pathogenic diagnosis the Hachinski and Gustafson-Nilsson scales were applied, while mental state was evaluated by the Folstein, Blessed, GDS and CDR tests. We performed in all cases cerebral CT and several MR. The findings associated with dementia were the presence of multi-infarctions, leucoaraiosis or lacunes in the cerebral CT and the presentation of new ischemic episodes, sphincterian or gait disturbances and focal deficits. There were no differences with the control group in the cases only presenting one TIA. Polyglobulia was the only factor significantly associated with vascular dementia in these patients. PMID- 8352973 TI - [The application of evoked potentials to the evolutive control of continuous spike/wave epilepsy during slow wave sleep]. AB - We studied 4 patients (14-21 years old) with continuous spike/wave epilepsy during slow wave sleep with visual evoked potentials (VEP) and somatosensory evoked potentials (SEP). All the patients presented the same focality and received the same medication (primidone plus sodium valproate). No case had another pathology not related with epilepsy which could alter the evoked potential findings. The results obtained in the initial evoked potentials were compared with those achieved after 5 years of treatment. In the initial study interhemispheric asymmetry in the latency of the early component (L.N1) of the SEP was observed with a mean of 10%. Five years later normal SEP were obtained with the asymmetry having disappeared thus leading to the deduction that the physiopathologic improvement found in these patients was due to the treatment of sodium valproate together with primidone. PMID- 8352974 TI - [Basic norms for the utilization of phenytoin by intravenous injection]. PMID- 8352975 TI - [Hemiplegia in posterior cerebral artery infarctions: analysis of various responsible mechanisms]. AB - When cerebral infarction determines hemiplegia or hemiparesia which accompany a hemilateral sensitive deficit and hemianopsia and even neuropsychologic symptoms (aphasic alterations in the case of injury to the left hemisphere, heminegligence and anosognosy in the case of injury to the right hemisphere) the involvement of a sylvian artery syndrome is usually considered. Nonetheless, recent contributions have reported that such symptoms may appear in infarctions of the territory of the posterior cerebral artery. Two clinical-radiologic observations in this line are presented. Nuclear magnetic resonance demonstrated injury to the posterior arm of the internal capsule in one case and in the other the lesion developed over three times, in the latter of which injury to the cerebral peduncle was produced causing hemiparesia. The authors emphasize that hemiplegia or hemiparesia in some infarctions of the posterior cerebral artery may be due to 1) mesencephalic infarction in the posterior plane of the retromamillar Foix and Hillemand pediculum (or G. Lazorthes interpedunculum), 2) infarction or "ischemic penumbra" in the internal capsule by involvement of any of the perforating branches of the posterior cerebrum irrigating the thalamus, except for the medial posterior choroid artery or even of the Foix and Hillemand thalamus-tuberian pediculum (or Lazorthes inferior and anterior) which principally initiates at the posterior communicating branch with a fragment of the posterior branch of the internal capsule perhaps not always being under its control. In this case, the thrombus occupying the posterior cerebrum may extend to the cited communicating branch or a hemodynamic deficit may be produced in the territory of the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8352976 TI - [The conduction of nerve impulses through MRIT2 hyperintense areas of patients with multiple sclerosis]. AB - Normal nerve impulse conduction through pathological areas has been documented but is believed to be rare in Multiple Sclerosis (MS). We present two patients with clinically definite Multiple Sclerosis, Poser's type 1a, in whom evoked potentials (EP) and magnetic resonance imaging (MRI) were performed for diagnostic purposes. The first patient had normal brainstem auditory evoked potentials (BAER) and normal somatosensory evoked potentials (SEP) despite a large unilateral midbrain lesion on MRI. The second patient had normal SEP and an extensive lesion in the cervical spinal cord. These findings demonstrate that normal transmission can occur through hyperintense areas, and the rise the problem of nature of the lesions in Multiple Sclerosis. PMID- 8352977 TI - [Disseminated encephalomyelitis. A study of 5 cases]. AB - Five cases of acute disseminated encephalomyelitis (ADE) with a follow-up longer than 5 years are presented. The clinical picture, CT images, MR and laboratory tests, specially LCR and evoked potentials presented in a variable form. In two cases the symptoms were preceded by viral infection. The course was acute in one case while the other four evolved in a subacute form during weeks. In two patients a pseudotumoral pattern was observed in the CT and MR images leading to difficulties in the diagnosis. Clinical improvement was accompanied by a partial resolution of the lesions. Steroid treatment improved symptomatology in all the cases. Knowledge of this process may avoid the unnecessary practice of other, more aggressive tests. PMID- 8352978 TI - [Pseudotumors as neurologic manifestation of Behcet disease]. PMID- 8352979 TI - [Myoclonic encephalopathy caused by lead intoxication]. PMID- 8352980 TI - Comparative analysis of anti-arrhythmic effect of propranolol and metoprolol in patients with supraventricular tachyarrhythmias. AB - Eighty-seven patients with paroxysmal tachydysrhythmias were submitted to clinical and laboratory evaluation and electrophysiologic studies were performed during the 3rd, 6th and 12th months of the therapy with propranolol or metoprolol. Metoprolol did not induce any significant change in sinoatrial correct time, in sinoatrial recovery time or in corrected sinoatrial recovery time. It decreases significantly the effective and functional AV refractory periods as well as increases the effective refractory period of the additional pathway. The mechanism of tachycardia preventing an involvement of the additional pathway in retrograde direction consists in the appearance of a block in the indicated additional pathway. The results of the humoral aspects are the following: propranolol inhibits the functions of the thyroid and sexual glands both in acute tests and in tests performed during the 3rd, 6th and 12th month of therapy; metoprolol has no significant effect on the functions of the thyroid and sexual glands; apparently, it influences the cardiac conduction system and myocardium directly. PMID- 8352981 TI - [Coronary thrombosis in patients who have died of acute myocardial infarct. A clinico-anatomical study of 167 successive cases]. AB - AIM: To determine the incidence of recent coronary thrombus in a population died of acute myocardial infarction (AMI) and to evaluate the relation between its presence and some clinical parameters (age, gender, time interval between the onset of symptoms and death and cause of death). POPULATION AND METHODS: 167 hearts of consecutive patients died of AMI and without thrombolytic therapy. Hearts were fixed in formaldehyde 10% for two weeks and then the epicardial coronary arteries were divided in 5 mm segments, which were examined by visual inspection to identify recent thrombi. Cuts for microscopical observation were obtained in cause of doubt. In each patients a clinical protocol with 64 parameters is performed. In statistical treatment Pearson's dispersion test and Student's t test were used. RESULTS: We found coronary thrombus in the infarction related artery in 74%. The thrombus distribution in the epicardiac coronary arteries was the following: 47% in the anterior descendent artery, 27% in the right coronary artery, 21% in the left circumflex and 5% in the left main. The comparison between the groups with and without coronary thrombus showed no differences in age and gender, but the time interval between AMI and death was shorter in the group with thrombus. Concerning the different causes of death (cardiac failure, cardiac rupture and others) the coronary thrombus prevailed in the group with left ventricule free wall rupture. There was no influence of the time interval between AMI and death on the larger prevalence of coronary thrombus found in cardiac rupture. CONCLUSIONS: The frequency of recent coronary thrombus in the infarction related artery was of 74% in this group of patients died of AMI without thrombolytic therapy. The presence of coronary thrombus was not related with patients age or gender. The frequency of coronary thrombus was inversely proportional to the time interval between AMI and death, and larger in the group with left ventricule free wall rupture. PMID- 8352982 TI - [The indices of pressure variability by noninvasive ambulatory monitoring of the arterial pressure. A study in 2 normotensive and hypertensive populations]. AB - OBJECTIVE: Analysis of different indices of blood pressure (BP) variability using the ambulatory blood pressure monitoring (ABPM) method in two populations of hypertensive patients (HTA Group) and normotensive volunteers (NOR Group). SETTING: Noninvasive prospective ambulatory study to assess the alterations of the circadian blood pressure profile through ABPM indices of blood pressure variability. PATIENTS: Patients with the diagnosis of essential arterial hypertension referred for clinical investigation to the Cardiology Department of Egas Moniz Hospital in Lisbon. MATERIAL AND METHODS: 40 hypertensive patients (HTA Group) and 30 normal subjects (NOR Group) were included in this study. We calculated the short and long term variability indices. The short term variability indices were the casual and mean immediate BP deviation, percentage of BP peaks and BP peak relative deviation and maximal range variation. Some clinical and general factors considered were namely age, gender, height, weight, body area and index, mean and casual systolic-diastolic blood pressure. RESULTS: Concerning systolic blood pressure in hypertension Vs normal groups respectively, the casual BP deviation was 15 +/- 4 mmHg and 7 +/- 4 mmHg (p 0.003), the mean immediate BP deviation was 18.5 +/- 4 mmHg and 7.5 +/- 3 mmHg (p 0.002), the percentage of BP peaks was 27 +/- 6% (p < 0.001), the percentage of BP peak area was 29 +/- 7% and 6 +/- 3% (p 0.001) and the percentage of relative deviation was 14 +/- 4% and 8 +/- 3% (p 0.03). For diastolic blood pressure all differences were not statistically significant between the two groups and the same happened for systolic blood pressure in relation to standard deviation and maximal range variation. Among these parameters and general and clinical characteristics, the systolic mean and casual blood pressure level showed an acceptable correlation with mean immediate deviation (R = 0.54/0.49), percentage of BP peaks (R = 0.56/0.49) and percentage of BP peak area (R = 0.60/0.53). CONCLUSIONS: Blood pressure variability can be adequately evaluated through the method of ambulatory blood pressure monitoring. Some variability indices can be extracted from the 24 hour curves of ambulatory blood pressure monitoring. Long-term variability indices are not related to the level of blood pressure. In the hypertension group we found a greater variability concerning short term indices, namely immediate deviation, percentage and are of peak curve. PMID- 8352983 TI - [A transesophageal color-coded pulsed Doppler echocardiographic study of the spatial distribution of mitral regurgitation jets]. AB - OBJECTIVE: Transesophageal echocardiographic analysis of color Doppler characteristics of mitral valvular regurgitation jets. DESIGN: Transesophageal echocardiographic prospective study. SETTING: Ambulatory patients referred to Echocardiographic Laboratory of Gregorio Maranon General Hospital, Madrid, Spain. MATERIAL AND METHODS: We studied a group of 100 consecutive patients with mitral regurgitation diagnosis. In each patient we calculated the degree of severity, percentage of wall intersection, maximal traced area, axis direction, atrial depth, maximal transversal diameter, perimeter and angle of the mitral regurgitation jet. We divided the entire population in three different groups according to the jet direction in central (CJ), eccentric (EJ) and wall jets (WJ). MAIN RESULTS: The direction of the mitral regurgitation jet was central in 49%, eccentric in 33% and impinging the left atrial wall in 18%. The mitral regurgitation jet angle was in the CJ 80 +/- 11 degrees, EJ 33 +/- 10 degrees and WJ 6 +/- 7 degrees. Maximal mitral regurgitant traced area in CJ was 732 +/- 104 mm2, EJ was 593 +/- 110 mm2 and WJ was 267 +/- 80 mm2. Maximal regurgitant jet depth in CJ was 36 +/- 17 mm, EJ 30 +/- 15 mm and WJ 49 +/- 14 mm. The perimeter of the mitral regurgitation jet in the CJ was 87 +/- 22 mm, EJ was 68 +/- 22 mm and WJ was 92 +/- 30 mm. CONCLUSIONS: Color Doppler quantification criteria are not useful in all patients with mitral regurgitation jets. The presence of atrial walls close to the mitral regurgitation jet area is an important factor in the mitral regurgitation color Doppler evaluation. PMID- 8352984 TI - [Pheochromocytoma--apropos a clinical case]. AB - A case of a 43-year-old woman with severe sustained hypertension resistant to many antihypertensive drugs, frequent hypertensive crisis and symptoms suggestive of pheochromocytoma (symptomatic triad) is presented. Three of the four determinations of the urinary catecholamines metabolites have been normal as it was the only determination of plasmatic catecholamines. Abdominal sonography and CT scan detected a left adrenal mass, that have been histologically confirmed, after surgery, to be a pheochromocytoma. After adrenalectomy, the patient symptoms disappeared but she maintained mild hypertension easily controlled with drugs. The finding of normal plasmatic and urinary catecholamines values in a patient with sustained hypertension may suggest that we are handling with a case of essential hypertension and a superimposed pheochromocytoma with paroxysmal secretion. Some considerations are made essentially about specificity and sensitivity of diagnostic tests. PMID- 8352985 TI - [Hemolytic anemia in the malfunction of a mitral bioprosthesis]. AB - Valvular cardiac prosthesis have dramatically altered the prognosis of patients with valvular cardiac disease; however, they are not free of complications. Prosthesis disfunction and problems related to anticoagulation are the more common, but hemolytic anemia should also be considered. In this case, hemolytic anemia appears as the major complication of a mitral bioprosthesis; the decision concerning the presentation of this case report rests upon its rarity and peculiar circumstances of appearance. A brief revision of the diagnostic work-up is also made. PMID- 8352986 TI - [Ketanserin as antioxidant]. AB - Free radicals have been related to the pathogenesis of some cardiovascular diseases. Several drugs used to treat these diseases were shown to have antioxidant properties. Our purpose was to evaluate if ketanserin, a selective S2 receptor antagonist with proven antihypertensive efficacy and which beneficially affects hemorheology, also is able to inhibit lipid peroxidation. Lipid peroxidation was induced in different biological systems in vitro and evaluated by the formation of thiobarbituric acid-reactive products. Ketanserin 50 microM inhibited copper-dependent lipid peroxidation in human red-cell suspensions by 40.8% and the subsequent hemolysis by 57,3%. It was less efficient in inhibiting hydrogen peroxide-dependent lipid peroxidation and hemolysis in the same system. Ketanserin 100 microM inhibited lipid peroxidation induced by a mixture of copper(II) and hydrogen peroxide in hepatic microsomal suspensions and in brain total homogenates by 86.2% and 56.7%, respectively. These results proved an antioxidant effect for ketanserin which was unknown, although its therapeutic relevance remains undetermined. PMID- 8352987 TI - [A double ambulatory product (blood pressure and heart rate), mild arterial hypertension and left ventricular hypertrophy]. AB - OBJECTIVE: Analysis of the different ambulatory blood pressure monitoring derived parameters in terms of cardiac structural repercussion, in patients with isolated systolic and mild systolic-diastolic hypertension. SETTING: Prospective study involving simultaneously the two-dimensional echocardiographic technique and the ambulatory blood pressure monitoring method. PATIENTS: Out patients regularly observed in the Cardiology Department of Egas Moniz Hospital in Lisbon, were included in our study. MATERIAL AND METHODS: We studied 50 hypertensive patients who fulfilled the inclusion criteria of our study (Group H) and 20 subjects who were the normal aged matched population (Group N). through ambulatory blood pressure monitoring, in each individual of these two groups, we considered the mean values of daily systolic blood and diastolic blood pressure, heart rate and ambulatory heart rate blood pressure product. Through two-dimensional echocardiography we calculated the left ventricular mass and the correspondent index corrected for the body surface. RESULTS: In the H group an comparing to the N group, the mean value of the daily systolic blood pressure was 112 +/- 6 mmHg and 159 +/- 8 mmHg (p < 0.001) respectively, diastolic blood pressure was 60 +/- 5 mmHg and 75 +/- 7 mmHg respectively (p < 0.001), heart rate blood pressure product was 6720 +/- 580 and 12561 +/- 678 (p < 0.0001) and of the left ventricular mass index was 109 +/- 10 gm2 and 145 +/- 7 g/m2 (p < 0.001). The correlation coefficient between the left ventricular mass index and mean systolic, diastolic blood pressures and ambulatory heart rate blood pressure product was 0.60 (p < 0.01), 0.45 (p = NS) and 0.73 (p < 0.001) respectively. CONCLUSIONS: In the evaluation of the increase in left ventricular mass, ambulatory heart rate blood pressure product is a more accurate parameter compared to the mean daily blood pressure values. Ambulatory blood pressure monitoring is a method with a great potential and clinical application, when studying patients with hypertension diagnosis. PMID- 8352988 TI - [Myocardial fibrosis--the theoretical bases, clinical aspects and therapeutic implications]. AB - A review on the present knowledges of the myocardial structure, with particular emphasis on the collagen network and its degradation/synthesis process was performed. Myocardial fibrosis and cardiac remodeling concepts are analysed, explaining them in the context of ventricular hypertrophy, arterial hypertension, myocardial remodeling in ischemic heart disease and cardiac remodeling in the aged. We also review the role of the renin-angiotensin-aldosterone system in myocardial fibrosis, as well as the results of preventing action of angiotensin converting enzyme inhibitors and aldosterone antagonists in myocardial fibrosis and consequent cardiac remodeling in the animal experimentation. Clinical and therapeutic implications of this knowledge are discussed as well as therapeutic implication in man, in view of recent studies. PMID- 8352989 TI - [In memoriam Dr. A. Chorao de Aguiar]. PMID- 8352990 TI - [Cochlear pathology following chronic electrical stimulation in cats]. AB - This study is to follow the faults during safe research of chronic electrical stimulation of auditory nerve. They were surgical trauma; electrode excursion from scala tympani in different periods after insertion, direct current trauma to the cochleas during chronic electrical stimulation due to the stimulator fault. Extensive histopathological changes were observed, including widespread hair cell and spiral ganglion loss and new bone growth. These results have important implications both in the use and design of cochlear prostheses. PMID- 8352991 TI - [Kanamycin ototoxicity and melanin in the inner ear]. AB - In order to clarify the relationship between ototoxicity of aminoglucoside and inner ear melanin, we have undergone observations on the cochleas of albino and pigmented guinea pigs with surface preparation, paraffin section. SEM and ECochG following chronic administration of kanamycin. The damage in the pigmented animal was more serious than that of the albino ones. It seems that the cochlea of the pigmented animal is more susceptible to kanamycin than that of the albino ones. It suggests that melanin may be implicated in the ototoxicity of aminoglucoside antibiotics that might be due to its capacity to take and accumulate the drug. PMID- 8352992 TI - [Reinnervation of posterior cricoarytenoid muscle: a comparison of nerve implantation and neuromuscular pedicle transfer in an animal model]. AB - Recently, methods of reinnervating posterior cricoarytenoid muscle (PCA) have been reported by many authors. This study was undertaken to compare direct implantation (NI) of a branch of the ansa cervicalis supplying the sternothyroid muscle with the transfer of a neuro-muscular pedicle of the ansa cervicalis innervating the sternothyroid muscle (NMP) in a denervated PCA dog model. Both were carried out immediately after denervation. The results showed that reinnervation with return of physiological function of PCA were got by both methods of nerve transfer. The NMP was apparently superior to the NI. The reason was that the NMP implanted more motor end-plates into the denervated PCA. So the NMP should be chosen first when possible. The NI is consistently effective when NMP is not available. PMID- 8352993 TI - [Evoked otoacoustic emission behavior in clinical sensorineural hearing loss]. AB - The present study revealed a significantly higher EOAE incidence in subjects with sensorineural hearing loss of unknown causes (81.82%) than in those with tumor of the cerebellopontine angle (42.86%), sudden deafness (41.38%) and equilibrium disorders (50%). EOAEs had been detected in some ears with mean pure-tone hearing threshold across 0.5, 1 and 2 kHz above 40 dB HL. For subjects with sensorineural hearing loss of unknown causes, the correlation coefficient between the mean hearing threshold and EOAE detection threshold amounted to only 0.40. It seems that EOAEs are related primarily to the nature of hearing loss rather than simply to pure-tone audiometric behavior. PMID- 8352994 TI - [Relation between pure tone audiometry and speech audiometry in various hearing impaired listeners]. AB - Pure tone audiometry and speech audiometry were performed in 30 normal-hearing listeners and 75 listeners suffering from conductive, sensorineural hearing loss or presbyacusia. The results were as follows: (1) For listeners with conductive or mild sensorineural hearing loss, or with mild presbyacusia, the difference between speech reception thresholds (SRT) and pure tone averages (PTA) was not significant (P > 0.05). (2) For listeners with profound sensorineural hearing loss or presbyacusia, the SRT were about 10 dB greater than the PTA. (3) The maximum discrimination score (PBXax) measurements should be made at a comfortable intensity for each listener, some 30 dB above the SRT in general. We conclude that the PTA can replace the SRT directly for the listeners described in (1) or that the PTA, by adding 10 dB, can also be used as a replacement of the SRT for the listeners described in (2). PMID- 8352995 TI - [Transcranial resection of tumors involving nose, paranasal sinuses and anterior skull base]. AB - Two cases of low-grade malignancies involving extensively the nose, paranasal sinuses, and anterior skull base were treated with transcranial resection and simultaneous repair of the dura as well as reconstruction of the skull base. The results appeared satisfactory. The advantages include: (1) much better cosmetic effect than the combined craniofacial resection. (2) almost equally full surgical exposure. (3) reliable repair and reconstruction of the anterior skull base with elimination of severe intracranial complications. PMID- 8352996 TI - [Study on lipid peroxides contents and superoxide dismutase activity in blood serum of elderly patients with head and neck carcinomas]. AB - The LPO contents and SOD activity were measured in blood serum of 110 elderly patients with head and neck carcinomas. The results showed that the LPO contents and SOD activity between the patients and control group (P < 0.01, P < 0.05) and the LPO contents between the metastatic group and non-metastatic group (P < 0.01) were significantly different. The LPO contents ascended (P < 0.01) by the 5th day and descended (P < 0.01) by the 14th day after operation. The relation between the occurrence and metastasis of the carcinoma and the LPO contents and SOD activity in blood serum was discussed. PMID- 8352997 TI - [Pharyngo-gastric anastomosis]. AB - Thirteen cases of laryngo-pharyngo-cervical oesophagus carcinoma were treated by pharyngo-gastric anastomosis and total laryngectomy. All patients after operation could swallow. The five-year survival rate was 1/4, three-year survival rate was 3/7 and one-year survival rate 9/13. We suggest that resection of pharyngo laryngo-esophageal, carcinoma with removal of all the pathological lesions and pharyngo-gastric anastomosis is the best way for the prophylaxis of recurrence when the carcinoma involves the cervical esophagus. Furthermore, due to the high tendency of metastasis to neck lymph nodes in the early stage of the carcinoma, neck dissection should be performed during operation. The advantages of pharyngo gastric anastomosis are wide indication and good blood supply. PMID- 8352998 TI - [The manifestation and significance of vimentin-9 in the otosclerotic stapes]. AB - Vimentin-9 is a special marker for identification of fibroblast. By the avidin biotin-peroxidase complex staining method, monoclonal anti-vimentin-9 was used to observe the role of fibroblasts in the development of otosclerosis. The results showed that fibroblasts were involved in the ossification process of the otosclerrotic lesions. Hence, the monoclonal anti-vimentin-9 might be an objective marker to identify the type and the developmental tendency of the otosclerotic process. PMID- 8352999 TI - [Changes of cochlear electrical activities in early experimental hydrolabyrinth]. AB - Changes of endocochlear potential (EP), cochlear microphonic potential (CM) and summating potential (SP) were studied in guinea pig cochlea after four weeks blockade of the endolymphatic sac and duct. The EP, CM and SP were measured with a microelectrode through the spiral ligament of the first turn. EP was decreased by 15%. The minimum CM output produced by tone burst of six frequencies (0.5, 1, 2, 4, 5 and 8 KHz) had reduced by 83.1%, 82.4%, 84.5%, 84.2%, 47.2% and 54.2% respectively, and the maximum CM output had declined by 54.3%, 41%, 43.2%, 21.1%, 26% and 24% separately. The minimum SP output caused by 4, 5 KHz tone burst had declined by 62.4% and 70.5%, and the maximum SP output had decreased by 41.5%, 45.2% in the early experiments. These results indicate that EP, CM and SP all underwent decreases. The extent of CM declination at low frequencies was larger than that at the high frequencies in the early experiments. The mechanisms of influence on EP, CM and SP in early experimental endolymphatic hydrops are discussed. PMID- 8353000 TI - NHS Efficiency Index: acute sector primacy yet again. PMID- 8353001 TI - The health care experience and health behaviour of the Chinese: a survey based in Hull. AB - Lack of knowledge about the health care experience and health behaviour of an important ethnic minority group prompted a study to inform the provision of health care and promote local action in Hull. Thirty Chinese 'takeaway' shops were randomly selected from the Yellow Pages of the Hull telephone directory, and all Chinese people working in them asked to complete a questionnaire. It contained questions on their knowledge, use and experience of primary health care and health promotion, together with aspects of their health behaviour. The same questionnaire in English was delivered to all workers in 30 fish and chip shops, to provide a White comparison group. Eighty (71 per cent) of the Chinese returned their questionnaire, and 73 (67 per cent) were returned from the chip-shop workers. The results indicate that the Chinese in Hull are not making optimal use of health services; they use some services inappropriately, whereas others, such as preventive health programmes, are under-used. One of the main reasons is identified as the language/communication difficulties faced by many Chinese. Other reasons are also highlighted and their implications discussed. The findings of this survey are in keeping with the mainly unpublished work undertaken elsewhere on this comparatively little researched ethnic minority group. PMID- 8353002 TI - Small area analysis: abortion statistics. AB - Small area analysis has developed over the last two or three decades as a useful tool in health services research, as it allows the identification of areas within health or local authority districts with high rates of morbidity and mortality, and thus provides a useful base for planning the delivery of health services. A profile was compiled for Liverpool Family Health Services Authority on planned parenthood in the Liverpool District, with the aim of identifying where resources are needed most - which parts of the City, and which groups of women, are most in need. The profile included an analysis of various outcome measures, including abortion statistics, which can be used as a guide to the apparent effectiveness of services. Using a combination of statistics on NHS abortions for electoral wards, and private abortions by postal district, it became apparent that, on the whole, areas of high NHS induced abortion rates also have high private (British Pregnancy Advisory Service; BPAS) induced abortion rates, and vice versa. The maps for NHS and BPAS abortion rates suggest that total abortion rates are high in City centre wards, and low in areas south of the City. This would suggest that there are differences in social factors, family planning provision, and other factors which are influencing abortion rates. Although available indicators would suggest that City centre wards are in greatest need of improved family planning provision, these are the wards which are relatively well provided with health authority family planning clinics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353003 TI - What price public aviaries? PMID- 8353004 TI - Social and behavioural predictors of women's cancer screening practices in Northern Ireland. AB - The aim of this study was to describe the extent of cancer screening practices among women resident in Northern Ireland and to identify the social and behavioural characteristics associated with these practices. The study involved a survey of adults resident in the community in Northern Ireland. Contact was made with a sample of 1162 residents who were asked to complete a questionnaire about preventive health practices and attitudes. This produced a response rate of 65.1 per cent. Of these, 391 were women who were asked questions about breast self examination (BSE), attendance for cervical screening, and certain social and behavioural factors. Approximately 28 per cent of the women performed BSE regularly, a further 28 per cent performed it occasionally, and the remainder rarely or not at all. Almost 20 per cent of the women had had a smear test once, 48 per cent several times, and the rest never. Performance of BSE and attendance for smear tests and BSE was more common among those women aged 35-54 years, who were married, worked outside the home, and whose religion was Church of Ireland (Anglican). The most frequent reason given for not performing BSE was fear of finding a lump and ignorance of the procedure. The most frequent reason given for non-attendance for a smear test was that it was not thought necessary at their age. Public health strategies designed to promote cancer screening need to consider the value of directing their campaigns at those who are most reluctant to perform these practices. PMID- 8353005 TI - Population screening for abdominal aortic aneurysm: do the benefits outweigh the costs? AB - To prevent the high mortality rate associated with ruptured abdominal aortic aneurysm (AAA), population screening at or soon after retirement age has been advocated, with elective operations being performed on patients with the appropriate indications. There is considerable pressure on some health authorities to fund such programmes even though there is substantial uncertainty about the consequent benefits. The ultrasound screening test is acceptable and accurate. Also, other health problems may be detected in the same screen. However, screening would lead to a questionable increase in surgery, as most patients with AAA die from other causes and not from a ruptured aneurysm. In addition, there is an elective operative mortality of around 5 per cent. Furthermore, as many of those who have a positive result on screening would never have known that they harbour an aneurysm, there is the possibility of unnecessary anxiety arising from the test. An economic analysis has been conducted for two identical, hypothetical cohorts of men using the best available data. One cohort was assumed to undergo screening and a number of men were indicated for immediate elective aneurysm repair or for follow-up, and surgery if their aneurysms become large. The other cohort was assumed not to be screened and would thereby face the possibility of rupture with its adverse outcome. The survival prospects of the two cohorts were calculated as life expectancies and in terms of life-years: the incremental life-years gained were compared with the incremental costs of the programme. Although there are considerable uncertainties in the analysis parameters, the base-line result and sensitivity analysis indicate that, on the basis of current knowledge, population screening should not be introduced. PMID- 8353006 TI - Are deprivation indicators a proxy for morbidity? A comparison of the prevalence of arthritis, depression, dyspepsia, obesity and respiratory symptoms with unemployment rates and Jarman scores. AB - The aim of the study was to examine the relationship between specific areas of morbidity measured using validated survey questions and deprivation indicators to see if the latter could act as a proxy in health needs assessment, health service planning and resource allocation in a typical health authority. A postal questionnaire was used to provide information about arthritis, depression, dyspepsia, obesity and respiratory symptoms in a simple random sample from the study population. The questions were from survey instruments that have been widely used to derive information about these conditions. The relationships between the prevalence of these specific areas of morbidity and both unemployment and the Jarman Underprivileged Areas Score were explored. Spearman's rank correlation coefficients were calculated and compared for each combination of measures. The study population was a random sample of the residents of each of the 22 electoral wards in Rotherham Health Authority. Responses were obtained from 82 per cent of the 5000 sampled. Although all morbidity measures showed positive correlations with both Jarman score and unemployment, some, notably those relating to respiratory disease and depression, were much more strongly correlated than others, such as obesity. There was no difference between unemployment and Jarman score in respect of the magnitude of the correlation coefficients. In conclusion, for some, but not all, conditions socio-economic measures are a good proxy for morbidity. Unemployment is just as useful a proxy as the Jarman score. PMID- 8353007 TI - Accidental injury attendances as predictors of future admission. AB - A case-control study was carried out in Nottingham Health District, to establish whether children under five years of age admitted to hospital after a accidental injury were more likely to have previously attended the accident and emergency (A & E) department than community controls. The subjects were 342 case-control pairs matched on sex and date of birth, consisting of children under five years resident in the Health District, and the main exposure measures were attendance at the A & E department before the case's first admission, type of injury and number of earlier attendances. It was found that, after adjusting for social deprivation score and proximity to hospital, children who had been admitted after an accidental injury were twice as likely to have attended the A & E department than community controls, and were more likely to have had more than one earlier attendance. Odds ratios were significantly raised for soft-tissue injuries and lacerations. It is concluded that accidental injuries in pre-school children that require attendance at the A & E department predict accidental injuries requiring admission. Making attendances at A & E departments notifiable to health visitors would facilitate the undertaking of accident prevention work. PMID- 8353008 TI - The process of evaluation of a new technology: genetic services and the introduction of DNA probes. AB - This paper gives a summary of the main results and recommendations, contained in reports for the Department of Health, of an evaluation of the introduction of DNA probes in the service activity of clinical genetics. The reports analysed cost and benefits of this technology, the potential demand for its use, the characteristics of the families referred to the service in terms of social and geographical distribution, the relative impact of DNA probes on the work-load of services in comparison with other activities, and the communication skills required by geneticists in relation to patients and other colleagues. However, the major element of this paper is the discussion of issues related to the process of evaluation. There has recently been discussion about ways to improve dissemination of results of health services research. We discuss here the major barriers that public health physicians and health service researchers need to address when playing the role of independent evaluators of services or new technologies. During the course of the evaluation of DNA testing, major changes occurred in the NHS. The evaluator will have to consider not only the costs and effectiveness of the new technology, but also how the findings are interpreted by the providers within the constraints of the new organizational structure. PMID- 8353009 TI - Death certification by house officers and general practitioners--practice and performance. AB - The objective of this study was to assess the knowledge, attitudes and behaviour of House Officers and General Practitioners (GPs) in relation to death certification, to determine the scope for future intervention. A postal questionnaire was used to survey all House Officers (174) and a 10 per cent random sample of GPs (131) in Mersey Region. The main outcome measures were: death certification experience; knowledge, attitudes and behaviour in relation to data uses and coding; and acceptability of Cause of Death statements. Response rates were comparable-119/174 House Officers (68.4 per cent) and 95/131 GPs (72.5 per cent). Most House Officers (78.8 per cent) and GPs (85.3 per cent) reported that they made the best possible Cause of Death statement but, respectively, 62.4 per cent and 59.3 per cent of these might modify a statement in some circumstances. Significantly more House Officers (70.3 per cent) than GPs (44.2 per cent) acknowledge room for improvement and were amenable to more training (86.6 per cent versus 52.5 per cent), but significantly fewer felt sufficiently instructed (23.7 per cent versus 52.6 per cent). Most respondents (> 90 per cent) considered accurate death certification important, but 46.2 per cent of House Officers had not read the death certificate book instructions. Knowledge was variable, especially concerning Underlying Cause of Death. Written Cause of Death statements were broadly similar in style and standard between groups. Experience did not appear to improve death certification practice. Better and co-ordinated undergraduate and early post-graduate education (which should be continuing and audited), and practical accessible guidance on death certificate completion, might improve standards of practice and performance within the existing framework. Alternative methods of presenting guidance on death certificate completion should be explored. PMID- 8353010 TI - Quarterly communicable disease review October to December 1992. From the PHLS Communicable Disease Surveillance Centre. PMID- 8353011 TI - PL(92)CO/4-neuro and ophthalmic surgery procedures on patients with or suspected to have, or at risk of developing, Creutzfeldt-Jakob disease (CJD), or Gerstmann Straussler-Scheinker syndrome (GSS) PMID- 8353012 TI - Neuro and ophthalmic surgery procedures on patients with or suspected to have, or at risk of developing, Creutzfeldt-Jakob disease (CJD), or Gerstmann-Straussler Scheinker syndrome (GSS) PMID- 8353013 TI - Colorectal cancer screening. PMID- 8353014 TI - The new Part I MFPHM examination. PMID- 8353015 TI - General practitioners, skin lesions and the new contract. PMID- 8353016 TI - Urban-rural health differences. PMID- 8353017 TI - [Immunogenetic factors in the onset of experimental tumors]. AB - The influence of immunological and genetic factors on the appearance of experimental tumors has been studied in mice by means of bidirectional selection. We found that the incidence of lymphomas, solid tumors and chronic nephritis is greater in mice selected for low antibody response than in mice selected for high antibody response. These findings suggest that the genes that control the antibody response also regulate life-span and resistance to neoplastic and inflammatory diseases. Similarly, we are carrying out bidirectional selective breeding to obtain two lines of mice, one sensitive and one resistant to the induction of cutaneous papillomas by chemical carcinogens. The two lines differ notably in terms of both percent of incidence and tumor multiplicity. The results of this study demonstrate clearly that resistance and susceptibility to carcinogenesis are subject to polygenic control. PMID- 8353018 TI - [The pharmacological therapy of glomerulonephritis]. AB - Clinical and experimental studies have markedly expanded our understanding of the causes of renal disease. Although they have not resulted in comparable therapeutic advances, new lines of treatment have emerged which cannot be underestimated. The prognosis of lipoid nephrosis has been substantially modified. The treatment of membranous glomerulonephropathy with steroids and immunosuppressive drugs may modify the course of the disease, at least in a subset of patients with decreased and deteriorating renal function. Encouraging results have been reported after the use of inhibitors of platelet aggregation in mesangiocapillary glomerulonephritis. We have demonstrated that a receptor antagonist of thromboxane can significantly influence the renal functional parameters in patients with lupus nephritis. ACE-inhibitors, cyclosporine and NSAID's have proved useful in reducing nephrotic proteinuria. Lipid lowering agents are able to ameliorate the glomerular lesions in experimental models of renal injuries. Since systemic hypertension may initiate the development of renal disease or accelerate loss of function in the kidney in which parenchymal disease is already established, controlling hypertension by any effective means helps to slow the progression of renal failure. Preliminary reports have suggested that there may be advantages to using ACE-inhibitors and/or calcium entry blockers. PMID- 8353019 TI - [Arterial hypertension in the black race]. AB - Hypertension represents a major health problem for black populations living in Western countries. In particular, blacks living in the United States have a three to fivefold greater mortality from hypertensive disease than do whites. Better knowledge of the pathophysiology of hypertension in blacks can aid in the treatment of recently urbanized black people coming to Italy from African countries. Hypertension occurs more frequently in blacks than in whites, due to increased volemia; this characteristic seems to be related to a genetically determined increase in sodium sensitivity. Environmental factors seem to play a relevant role. Several studies performed on blacks migrating from rural to urban areas both in Africa and the USA, have shown that urbanization is closely related to increased blood pressure. The occurrence of cardiac and cerebrovascular complications of hypertension also seems to be closely related to socioeconomic factors. In fact, recently immigrated black people often lack health care facilities and consequently have poor control of hypertension. The environmental factors could be overcome by implementing systems to improve health care facilities, in particular blood pressure control, for recently urbanized blacks. PMID- 8353020 TI - [Osteoporosis and fractures: a review of current therapies]. AB - The authors examine the effects of different drugs used in osteoporosis therapy for the primary and secondary prevention of fractures. They base their review on prospective randomized studies; retrospective studies are included only if a consistent number of subjects has been examined. Their methodological characteristics are illustrated, and results with significant levels and 95% confidence intervals are reported. Only hormone replacement therapy and salmon calcitonin have been demonstrated as able to prevent vertebral and non-vertebral fractures. Vitamin D and its analogues seem to be effective only in elderly patients, although conclusive data are lacking. With regard to bisphosphonates, only data on vertebral fractures are presently available. Results from fluoride studies are still very inconclusive, and, in fact, lead to the hypothesis of a fracture-promoting effect. At present, no data on ipriflavone are available. Considerably more research is necessary to define the efficacy of different treatment protocols for fracture prevention. Each therapeutic proposal for osteoporosis should be supported by data on its efficacy in reducing the incidence of fractures. Not always, in fact, is an absolute increase of bone mass followed by the effective prevention of fractures. At this time, only estrogens and calcitonin have been demonstrated as able to reduce fracture incidence. PMID- 8353021 TI - [Hypothyroid myopathy in a young adult]. AB - We describe here the case of a young man admitted to our department for asthenia and diffuse myalgia. Because of persistently increasing aminotransferase levels over the preceding 2 years, he had undergone a number of diagnostic procedures to evaluate liver function. On admission to our department, the patient suffered from asthenia, myalgia, notable hair loss and sinus bradycardia. Laboratory examinations confirmed severe primary hypothyroidism with high serum levels of aminotransferase, aldolase and creatine-phosphokinase attributable to thyroprivic myopathy. The thyroid deficit was caused by autoimmune atrophic thyroiditis. Treated with levothyroxine, the patient recovered fully from his illness, his normal metabolic state was restored, and his serum aminotransferase level returned to normal. PMID- 8353022 TI - Dialysis and transplant patients in the long term. AB - The history of renal replacement therapy is traced from the early days of dialysis and kidney transplantation through the era of miraculous technology and the alleged certainties of anti-rejection therapy. Attention is focused on the newly found or anomalous biotypes that are common to both dialysis and transplantation. In dialysis not only the patient but also uremia is maintained and either hyper- or hyporeactivity in different biological systems may occur with or without clinical symptoms. In transplantation, while the balance between immunomodulation and immunotolerance is far from ideal, extrarenal complications may occur with an atypical mode of presentation, serious immunological renal lesions may develop asymptomatically and clinical signs of rejection may appear without noticeable laboratory alterations. PMID- 8353023 TI - [The autocrine-paracrine modulation of natural killer activity in man by peptides of the corticostatin-defensin family]. AB - Corticostatins (CS)-defensins are a family of peptides recently isolated from neutrophils and cells of myeloid lineage. They have been termed CS in that members of the family inhibit ACTH-induced steroidogenesis, and defensins in that they are highly effective as enhancers of intracellular killing of pathogens. Natural killer (NK) cells are an immunocyte subset whose cytotoxic activity is modulated by lymphokines and hormones. Recent evidence suggests a myeloid origin for these cells. We evaluated whether two human CS-defensins, HP-1 and HP-4, are able to modulate in vitro spontaneous NK cell activity of human peripheral blood mononuclear (PBM) cells and in vitro susceptibility to the stimulatory effect by immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory effect of cortisol. PBM cells were incubated for 20 h with HP-1 or HP-4 and IFN gamma or IL-2 or cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay (K562 cells as a target). We also searched for CS-defensins in NK-enriched cell preparations by means of HPLC separation of the supernatant obtained from sonicated cells. HP-1 and HP-4 significantly inhibited both spontaneous and lymphokine-inducible NK cell activity, and potentiated cortisol dependent inhibition. Radioimmunoassay on HPLC purified fractions demonstrated the presence of HP-1 in NK-enriched cell preparations. Our data indicate that HP 1 and HP-4 are negative modulators of NK cell cytotoxicity and that autocrine/paracrine mechanisms are conceivably involved. HP-1 production by NK cells may be viewed as additional support for the thesis of the myeloid origin of these immune effectors. PMID- 8353024 TI - [The gastric anatomico-functional aspects (parietal cell mass, stimulated acid secretion and gastrinemia) in pernicious anemia]. AB - We present here a study of parietal cell mass, stimulated acid secretion and basal gastrinemia both in the course of isolated chronic atrophic gastritis of the body-fundus and in chronic atrophic gastritis of the body-fundus associated with pernicious anemia. Analysis of our results evidences an overlapping cyto secretory profile characterized by hypoparietalism with hypo-achlorhydria. The higher basal gastrinemia levels in pernicious anemia depend on the histological status of the antral mucosa--which was always normal in the patients with pernicious anemia--rather than any substantial morpho-functional differences of the body-fundus. We thus conclude that the term "atrophic gastritis" should be abolished, and that the term "chronic atrophic gastritis" be used to describe both conditions. PMID- 8353025 TI - [Sodium-modulating hormones and the pressor response to sodium chloride in essential arterial hypertension]. AB - Some predictive markers for NaCl sensitivity, related to the red blood cell membrane or to circulating proteins, have already been described in human essential hypertension. The present study was planned to investigate whether or not some hormones produced by the kidney or acting at the kidney level could be used as new markers for NaCl sensitivity. The study was conducted in 28 not previously treated outpatients affected by uncomplicated mild to moderate essential hypertension. After 15 days on a normal NaCl diet, plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP), and the urinary excretion of active kallikrein were evaluated. The sensitivity of blood pressure to changes in NaCl intake was then assessed in all patients, according to a randomized double blind cross-over design. Each patient was assigned to a high (240 mmol of NaCl/day for 15 days) or low (40 mmol of NaCl/day for 15 days) NaCl intake. During the assessment of NaCl sensitivity, the double blindness was achieved by the use of capsules containing either NaCl or placebo. Fifteen patients (11 males and 4 females) resulted as NaCl-sensitive, while 13 patients (8 males and 5 females) were classified as NaCl-resistant. Our results indicate that PRA levels were significantly lower in the NaCl-sensitive group than in the NaCl-resistant one (0.108 +/- 0.05 ng/L/s vs 0.247 +/- 0.16 ng/L/s, p < 0.007), in the presence of raised levels of plasma ANP in NaCl-sensitive hypertensives (18.08 +/- 4.61 fmol/mL vs 12.45 +/- 3.77 fmol/mL, p < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353026 TI - [Current advances in various aspects of chronic obstructive bronchopneumopathy and in the pathogenesis of bronchial asthma]. AB - The continuing interest of researchers in chronic obstructive pulmonary disease (COPD) is due not only to its increasing socio-economic impact, but also to the rapid advances made in the comprehension of various mechanisms of this disease, advances made feasible chiefly by a broader interdisciplinary approach to the subject. The most significant progress has been made through the study of bronchial asthma: researchers have confirmed that a particular inflammation of the bronchial mucosa is the common feature of all asthmatic syndromes. IgE antibodies specific for allergens as well as Th2 type T cells seem to play a central role in allergic bronchial asthma. Other types of T cells producing different combinations of cytokines, chiefly IL-5, may be involved in the pathogenesis of intrinsic and professional asthma. It is hoped that this recently gained knowledge will enable improvement in the prevention and therapy of asthma and other COPD syndromes. PMID- 8353027 TI - Expanded programme on immunization (EPI). Reassessment of the neonatal tetanus problem. PMID- 8353028 TI - Potential years of life lost before age 65, 1990 and 1991. PMID- 8353029 TI - Update: International Task Force for Disease Eradication. 1992. PMID- 8353030 TI - Expanded programme on immunization (EPI). Poliomyelitis eradication activities in Shandong Province. PMID- 8353031 TI - Mass vaccination campaigns to control the 1991-1992 poliomyelitis outbreak. PMID- 8353032 TI - Helix pomatia and prognosis of breast cancer. PMID- 8353033 TI - Current statistical issues in clinical cancer research. PMID- 8353034 TI - Surrogate endpoints. PMID- 8353035 TI - Involvement of RET oncogene in human tumours: specificity of RET activation to thyroid tumours. AB - Non-thyroid neoplasia were analysed by Southern blot of genomic DNA and DNA prepared by reverse transcription and amplification by polymerase chain reaction (RT/PCR) for the activation of the RET oncogene. It is known that the rearrangement of RET occurs in about 10%-20% of human thyroid papillary carcinomas. None of 528 non-thyroid tumours showed rearrangement of the RET proto oncogene, whereas three out of 30 thyroid papillary carcinomas were positive for RET activation. Therefore the activation of RET seems to be a somatic cell mutation specific to human thyroid carcinomas. PMID- 8353036 TI - Interleukin-1 beta and interleukin-6 release by peripheral blood monocytes in head and neck cancer. AB - In patients with advanced head and neck squamous cell carcinoma (HNSC), evidence of cell-mediated immunity and monocyte functional abnormalities has been reported. We studied the production of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by peripheral blood monocytes from 22 patients with HNSC (12 larynx and ten oral cavity cancers) in comparison with monocyte cytokine production of age-matched healthy subjects. Pure monocytes were incubated with and without lipopolysaccharides (LPS) (10 micrograms ml-1) for 4 h at 37 degrees C and IL-1 beta and IL-6 concentrations were determined in supernatants by specific ELISA. There was no significant difference in IL-1 beta levels in monocyte supernatants from cancer in comparison to control subjects; conversely, a higher IL-6 production by unstimulated and LPS-activated cells from HNSC patients than from controls was found. No relationship was observed between cytokine production and cancer stage. The regression analysis evidenced a significant correlation between IL-1 beta and IL-6 monocyte-release in HNSC patients and in controls, so suggesting a possible autocrine control of IL-6 production by other cytokines. PMID- 8353037 TI - Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats. AB - Acute haematological toxicity induced by cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) and cis-diamminedichloroplatinum (II) (cisplatin) in combination with whole body hyperthermia (WBH) (2 h at 41.5 degrees C) was examined using a F344 rat model. The thermal enhancement ratios (TERs) of drug-mediated thrombocytopenia, anaemia and leukopenia were determined from the dose-response curves of the nadir values of the peripheral platelet, RBC and WBC counts. Carboplatin produced profound depression of platelet counts which was over three-fold greater than cisplatin (14% vs 51% of the control), while the decrease in WBC and RBC counts induced by carboplatin did not differ significantly from those observed with cisplatin. These carboplatin or cisplatin mediated haematological toxicities were significantly enhanced by WBH. The depth of decrease in platelet, RBC and WBC counts induced by the maximum tolerated dose (MTD) of carboplatin (30 mg kg-1) combined with WBH was identical to that induced by the MTD of carboplatin (70 mg kg-1) alone. The TERs of carboplatin-mediated thrombocytopenia, anaemia and leukopenia were 2.0, 2.8 and 1.9, respectively. The thermal enhancement of cisplatin mediated haematological toxicity was similar to that of carboplatin, with TERs of 1.8 for thrombocytopenia, 2.4 for anaemia and 1.9 for leukopenia. These data, demonstrating thermal enhancement of cisplatin or carboplatin-mediated haematological toxicity, must be taken into account in the clinical application of the combination therapy of platinum and WBH. PMID- 8353038 TI - Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists. AB - The 50% survival time for low grade astrocytomas is 50 months and for high grade astrocytomas it is 13 months, underlining the need for new therapies. Several reports show that in vivo histamine antagonists cause retardation of tumour growth in some animal models and prolonged survival in cancer patients. Therefore we have tested the growth modulating effects of histamine and histamine antagonists on human glioma cultures. Twelve freshly excised human gliomas were cultured and tested for their in vitro sensitivity to histamine and histamine antagonists. Four continuous glioma cell lines were used to confirm the glioma specificity of the effects observed in the primary cell lines. In low serum concentration (0 or 1%) the growth of 5/9 primary glioma-derived cultures could be stimulated with 0.2 mM histamine, and in 4/5 cases with 0.2 microM histamine. One mM of the histamine H2-receptor antagonist cimetidine could inhibit the growth of 4/5 primary glioma cultures when tested in 1% human AB serum, and of 6/13 cases when tested in 1% FCS. Lower concentrations (down to 1 microM) were less effective. The histamine H1-receptor antagonist pyrilamine gave variable results. The specificity of the effects is indicated by the absence of a generalised toxic effect, by the observation that the antagonist-induced inhibition could be reversed with histamine, and by the correlation of the obtained cimetidine-induced growth inhibition with the maximal growth rate of the primary cell lines in 10% FCS. The observed cimetidine-induced inhibition of the in vitro proliferation of gliomas suggests that cimetidine is a relevant candidate for the in vivo growth inhibition of these tumours. PMID- 8353039 TI - pH in human tumour xenografts: effect of intravenous administration of glucose. AB - pH frequency distributions of tumours grown s.c. from 30 human tumour xenograft lines in rnu/rnu rats were analysed with the use of H+ ion-sensitive semi microelectrodes prior to and following stimulation of tumour cell glycolysis by i.v. infusion of glucose. At normoglycemia, the average pH of the tumours investigated was 6.83 (range, 6.72-7.01; n = 268). Without exception, all xenografts responded to the temporary increase in plasma glucose concentration (PGC) from 6 +/- 1 to 30 +/- 3 mM by an accumulation of acidic metabolites, as indicated by a pH reduction to an average value of 6.43 (range, 6.12-6.78; n = 292). This pH value corresponds to a ten-fold increase in H+ ion activity in tumour tissue as compared to arterial blood. Tumour pH approached minimum values at 2-4 h after the onset of glucose administration and could be maintained at acidic levels for 24 h by controlled glucose infusion. Irrespective of pH variations between tumours grown from individual xenograft lines, there was no major difference in pH response to glucose between the four main histopathological tumour entities investigated, i.e. breast, lung and gastrointestinal carcinomas, and sarcomas. In tumours from several xenograft lines, an increase in blood glucose to only 2.5-times the normal value (14 mM) was sufficient to reduce the mean pH to 6.4. Glucose-induced acidosis was tumour specific. The pH frequency distributions in liver, kidney and skeletal muscle of tumour-bearing rnu/rnu rats were only marginally sensitive to hyperglycemia (average pH, 6.97 vs normal value of 7.14). Tumour-selective activation of pH sensitive anti-cancer agents, e.g. alkylating drugs, acid-labile prodrugs or pH sensitive immunoconjugates may thus be feasible in a wide variety of human cancers. PMID- 8353040 TI - Intra-tumoral heterogeneity of tumour potential doubling times (Tpot) in colorectal cancer. AB - Intra-tumoural heterogeneity of proliferation has been assessed by taking multiple biopsies from 30 colorectal cancers. Following in vivo IUDR labelling, dual parameter flow cytometry was used to measure tumour DNA index (DI) and labelling index (LI) and to derive DNA synthesis time (Ts) and potential doubling time (Tpot). Heterogeneity was seen for all parameters under investigation. Overall coefficients of variation (CV) and logarithmic transformation of Ts and Tpot (due to their non-gaussian distributions) indicate that LI (CV 25%) was the most variable parameter. Intra-tumoral heterogeneity in Tpot (lnTpot CV = 22%) was less than inter-individual variation (CV = 63%), suggesting that this variation should not be a limitation to the possible usefulness of this technique as an independent prognostic indicator. Correlations of Tpot values were examined between the shortest, the median and the value for a pooled homogenate sample from a single tumour. Using an homogenate, it was possible to accurately predict classification of tumour Tpot values as being below the median ('fast tumours') in 15 of 19 cases (79%). The data suggest that assaying an homogenate may allow a more rapid analysis of a multiply sampled tumour. PMID- 8353041 TI - Loss of cell-cell and cell-matrix adhesion molecules in colorectal cancer. AB - Adhesion molecules are thought to play a vital role in the induction and maintenance of tissue differentiation and their loss or down-regulation has been implicated in the neoplastic process. Recent studies have shown that the morphoregulatory activities are a consequence of interactive processes between several cell adhesion molecules rather than the function of a single molecule. Therefore, we have investigated a panel of adhesion molecules including members of the integrin, cadherin and immunoglobin superfamily in colorectal cancer. Twenty-eight consecutive colorectal adenocarcinomas were stained using an avidin biotin indirect immunoperoxidase technique. Our results showed a consistent loss of the alpha 2 and beta 1 integrin subunits (21/28 = 75% and 22/28 = 78.6% respectively) and a decrease in expression of E-cadherin in 5/5 poorly differentiated adenocarcinomas. Carcinoembryonic antigen expression was preserved but with basolateral accentuation seen in tumours. There was no statistical correlation with Dukes' stage. These results provide further evidence that in colorectal cancer there is a widespread deregulated expression of cell-cell and cell-matrix adhesion molecules. Changes in the expression and function of adhesion molecules which regulate growth and differentiation may play a role in the behaviour of colorectal cancer. PMID- 8353042 TI - Enhancement by thyroxine of gastric carcinogenesis induced by N-methyl-N'-nitro-N nitrosoguanidine in Wistar rats. AB - The affects of L-thyroxine (T4) on the incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the labelling index of gastric mucosal epithelial cells were investigated in Wistar rats. After oral treatment with MNNG for 25 weeks, the rats received s.c. injections of T4 (0.2 microgram kg-1) in depot form every other day until the end of the experiment in Week 52. This long-term treatment with T4 significantly increased the incidence of gastric cancers in Week 52. However, it did not influence the histological type of the gastric cancers. It also caused significant increases in the labelling indices of the fundic and antral epithelial cells. These findings indicate that T4 enhances the development of gastric cancers, and that its effect may be related to its effect in increasing proliferation of gastric epithelial cells. PMID- 8353043 TI - Retinoic acid receptors in retinoid responsive ovarian cancer cell lines detected by polymerase chain reaction following reverse transcription. AB - The growth inhibitory effects of all-trans and 13-cis retinoic acid (RA) and of the synthetic retinoids TTNPB, TTNPB-ethylester and TTNN were studied on seven human epithelial ovarian cancer cell lines and one ovarian teratocarcinoma cell line. Six of seven ovarian adenocarcinoma cell lines were inhibited in their growth by RA and by synthetic retinoids in a dose dependent manner. No response to these substances was observed for the ovarian teratocarcinoma cell line. The knowledge that RA and retinoids exert their action on the cells via nuclear receptors led us to examine the expression of RAR-alpha, -beta and -gamma mRNA by these cell lines by polymerase chain reaction following reverse transcription. All cell lines expressed RAR-alpha and -gamma mRNA and six of the eight cell lines were found to express additionally RAR-beta mRNA, among them the ovarian teratocarcinoma cell line. Our data indicate that there was no direct association between the presence of RAR subtype transcripts and the response to retinoids in ovarian cancer cell lines. PMID- 8353044 TI - Bioavailability and feasibility of subcutaneous 5-fluorouracil. AB - Continuous intravenous (i.v.) infusion of 5-fluorouracil (5-FU) has been shown to be superior to bolus regimens in terms of response rates and toxicity. However, a continuous infusion is more expensive and prone to complications such as thromboembolism and infections. A way to circumvent these problems would be to administer 5-FU subcutaneously (s.c.). To assess feasibility and bioavailability of s.c. 5-FU, eight patients with advanced cancer received 250 mg 5-FU as an infusion over 90 min either intravenously (i.v.) or s.c. into the abdominal wall. The mean +/- s.d. bioavailability of s.c. 5-FU was 0.89 +/- 0.23. The interpatient variability for the area under the plasma concentration-time curve was 48% for the s.c. and 36% for the i.v. infusion. No local side effects were observed. To test the local tolerance of a more prolonged administration three patients received 930-1,000 mg m-2 5-FU by 24-h continuous s.c. infusion. The steady-state plasma levels were comparable to i.v. infusion. One patient developed a painless skin pigmentation at the s.c. infusion site. However, the same reaction was observed at the forearm after i.v. infusion. We conclude that at the dose studied s.c. 5-FU has an almost complete bioavailability and is well tolerated. Further work will show, whether prolonged s.c. infusion can be used as a safe and economical alternative to i.v. infusion. PMID- 8353045 TI - Scintigraphic evaluation of functional hepatic mass in patients with advanced breast cancer. AB - Recent studies suggest a high specificity of 99mTc-galactosyl neoglycoalbumin (99mTc-NGA) receptor scanning in vivo by providing both morphological and functional diagnosis of liver disease. In 22 patients with advanced breast cancer 99mTc-NGA (150 MBq; 50 nmol) was exclusively trapped by the liver, the images showing 'cold spots' in areas of liver metastases formation. A two-tailed analysis was performed: the time activity curves recorded for the liver and precordial area were subjected to a kinetic receptor-calculating model allowing an estimation of the NGA-receptor concentration of the liver (i.e. hepatic binding protein, HBP) as well as calculation of the residual functional liver volume (RFLV) via the S.P.E.C.T.-study. In breast cancer patients with liver metastases a significantly (P < 0.01) lower HBP-concentration was estimated (0.65 +/- 0.16 vs 0.82 +/- 0.17 mumol l-1) as evidenced by a lower 99mTc-NGA accumulation in the liver resulting also in a significantly (P < 0.001) lower RFLV (739 +/- 348 vs 1336 +/- 184 ml). In four amonafide-treated patients (800 mg m-2 intravenous infusion over 3 h) approximately one week after one chemotherapy cycle a significant (P < 0.05) increase in HBP-concentration (0.56 +/- 0.10 vs 0.72 +/- 0.06 mumol l-1) of the liver was found corresponding with an increase in RVLF (546 +/- 297 vs 670 +/- 265 ml). These regulatory mechanisms at the HBP level measured in vivo provide further evidence that 99mTc-NGA should have promise as a clinically useful receptor radiopharmaceutical for both quantification of liver function and assessment of liver morphology. PMID- 8353046 TI - A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer. Part II: Immunological aspects. AB - Previously we described the clinical aspects of a phase I study of prolonged continuous infusion of low-dose recombinant interleukin-2 (rIL-2). In the present paper we report several immunological effects in 13 patients with melanoma and renal cell cancer treated on an out-patient basis with rIL-2 for uninterrupted periods ranging from 5 to 18 weeks. Groups of three patients were treated at following dose levels 0.18, 0.6, 1.8 or 6 x 10(6) IU m-2 24 h-1 and one patient was treated with 3 x 10(6) IU m-2 24 h-1. Prolonged rIL-2 treatment resulted in a dose-dependent and sustained increase in the percentage and absolute number of (CD56+, CD8dim) natural killer cells. Within this population a preferential increase in the CD56bright cells with low expression of CD16 was observed. The CD27 antigen was also upregulated in the CD56bright CD16dim population. This increase of NK cells was accompanied by an enhancement of the cytotoxic capacity of the peripheral lymphocytes. No consistent signs of T cell activation or expansion were noted. PMID- 8353047 TI - Oral contraceptives and breast cancer in northern Italy. Final report from a case control study. AB - To assess the relation between oral contraceptive (OC) use and breast cancer, we analysed data from a case-control study conducted in Northern Italy between 1983 and 1991 on 2,309 cases below age 60 and 1,928 controls admitted to hospital for acute diseases unrelated to OC use and to any of the known or potential risk factors for breast cancer. OC use was reported by 16% of cases and 14% of controls. The multivariate relative risk (RR) for ever vs never use of combination OC was 1.2 (95% confidence interval (CI) 1.0-1.4). However, there was no trend in risk with duration. The RR was elevated for very short use, but declined to 0.8 (95% CI = 0.5-1.0) for five or more years' use. No noteworthy relationship was found for other major measures of OC use, although RR estimates were above unity for women who had stopped use less than 5 years before (RR = 1.5, 95% CI = 1.1-2.0), started use less than 10 years before (RR = 1.3, 95% CI = 1.0-1.9), started when 25 or more years old (RR = 1.4, 95% CI = 1.1-1.7), or after first birth (RR = 1.2, 95% CI = 1.0-1.5). No interaction was observed between OC use and family history of breast cancer, parity and age at first birth. A separate analysis of 373 cases and 456 control below age 40 showed no association with ever use (RR = 0.9, 95% CI = 0.6-1.2). PMID- 8353048 TI - Past and present physical activity and endometrial cancer risk. AB - We examined the relation between physical activity and endometrial cancer using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. Estimates of recreational (i.e. active sport, walks and hikes) and nonrecreational activity (i.e. house cleaning, climbing stairs and walking or standing on the job) were obtained using interview information. After adjustment for age, study area, education, parity, years of use of oral contraceptives, years of use of menopausal oestrogens and cigarette smoking, recent recreational inactivity was associated with increased risk (RR = 1.9 for lowest vs highest tertile). Similarly, recent nonrecreational inactivity was associated with increased risk (RR = 2.2 for lowest vs highest tertile). Further adjustment for body mass and nonrecreational activity attenuated the association between risk and recent recreational inactivity (RR = 1.2; 95% CL = 0.7-2.0) but adjustment for body mass and recreational activity did not alter the association between risk and recent nonrecreational inactivity (RR = 2.0; 95% CL = 1.2-3.1). To evaluate the relation between risk and sustained inactivity, we simultaneously examined activity levels at three periods (RR i.e. age 20-29, age 30-39 and recently) in women age 50 and older. After adjustment for potential confounders and body mass, risk was elevated among women who were always recreationally inactive (RR = 1.5 for always active vs always inactive) and among women who were always nonrecreationally inactive (RR = 1.6 for always active vs always inactive). This study suggests that physically inactive women may be at increased risk of endometrial cancer because they are more likely to be overweight or obese. Our data also suggest that inactivity per se may be associated with an increased risk of endometrial cancer. However, we cannot rule out the possibility that our results, particularly those for nonrecreational activity, reflect unmeasured confounding factors. Future studies should attempt to obtain more detailed assessments of physical activity, including the intensity with which an individual engaged in an activity and the actual time involved in exertion. PMID- 8353049 TI - Depletion of circulating cyst(e)ine by oral and intravenous mesna. AB - The sulfhydryl status of normal and tumour cells is critically important in determining their susceptibility to various cytostatic agents. As a sulfhydryl compound, mesna (sodium 2-mercaptoethane-sulfonate) which is used in large doses to prevent haemorrhagic cystitis associated with certain chemotherapeutic regimens might derange cellular thiol homeostasis. In order to investigate the effects of mesna on the concentrations of thiols in plasma, cysteine, glutathione and their disulfides were measured by HPLC following the oral and intravenous administration of mesna to healthy volunteers. After 7.3 mmol mesna i.v. free cysteine rose from 8.2 (95% CI 7.0-9.4) nmol ml-1 to 53.6 (47.4-59.8) nmol ml-1 at 5 min, most likely due to reduction of circulating cystine by the sulfhydryl drug. This initial rise was followed by a marked decrease of total cyst(e)ine in plasma from 276 (215-337) nmol ml-1 to a nadir of 102 (89-115) nmol ml-1 between 30-120 min after infusion, most likely due to an increased uptake of cysteine into cells and an increased urinary excretion of cyst(e)ine. Qualitatively similar changes were seen after oral mesna. The present data indicate that mesna depletes circulating cyst(e)ine and may thereby markedly alter the sulfhydryl status of cells in vivo although the drug itself is not taken up by most cells. PMID- 8353050 TI - EPIC: an effective low toxicity regimen for relapsing lymphoma. AB - We have treated 40 patients was relapsed or resistant lymphoma with the combination of Etoposide, Prednisolone, Ifosfamide and Cisplatin (EPIC). Complete response was obtained in 11 patients (28%) with an overall response of 58%. The presence of bulky disease (P < 0.005), elevated LDH serum levels (P < 0.005), response to prior chemotherapy (P < 0.01) and B symptoms (P < 0.005) were significantly associated with response. However on multivariate analysis only the presence of bulky disease and of B symptoms were independent adverse factors for response and for survival. The regimen was well tolerated with myelosuppression being the most common toxicity. Leucopenia < or 1,000 microliters-1 and thrombocytopenia < or = 25,000 microliters-1 developed in 27% and 4% of cycles respectively. There were no treatment related deaths. The EPIC regimen has equivalent activity to other reported cisplatin based regimens used in the treatment of recurrent lymphoma, but is associated with lower treatment related morbidity and mortality. PMID- 8353051 TI - Primary carcinoma of the fallopian tube--a retrospective analysis of 115 patients. Austrian Cooperative Study Group for Fallopian Tube Carcinoma. AB - Incidence and prognostic factors of primary carcinoma of the Fallopian tube were studied in a retrospective multi-centre analysis of 115 women during the period 1980 to 1990. Data of 28 departments (university as well as general hospitals) were included in the present study which was designed to evaluate the current diagnosis and treatment of carcinoma of the Fallopian tube in Austria, and to compare the results with those from the literature. Stages were classified according to the modified FIGO-system for ovarian cancer; grading followed the criteria of Hu et al. (1950). The mean age of the patients was 62.5 years. Forty seven (40.9%) tumours were found to be in stage I, 20 (17.4%) in stage II, 34 (29.6%) in stage III, and 14 (12.1%) in stage IV. In 82 patients, the tumour could be completely removed. The surgical method applied in 95 cases was removal of the uterus, the adnexa, and/or the omentum, or lymph nodes. Postoperatively patients underwent adjuvant therapy which was either irradiation (n = 40; 34.8%), or chemotherapy (n = 49; 42.6%); 26 women (22.6%) had no therapy after operation. The 5-year survival rate for all stages was 36.5%. In stages I and II the 5-year survival was 50.8% compared to 13.6% in stages III and IV. FIGO-stage I and II and a residual tumour less than 2 cm in advanced disease had a prognostically favourable impact, which was proven in univariate as well as multivariate analysis. PMID- 8353052 TI - The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck. AB - We have examined the incidence of Harvey ras mutations in human squamous cell carcinomas (SCC) of the upper aerodigestive tract using the polymerase chain reaction (PCR) followed by direct sequencing. No mutations were detected at codons 12, 13, 59 or 61 of this gene in any of six papillomas, five erythroplakias, 56 squamous cell carcinomas, and 16 SCC cell lines. Some of the SCC were lymph node metastases (three) or tumours which had recurred following radiotherapy (seven). We conclude that Harvey ras mutations are not a common event in the pathogenesis or recurrence of SCCs from Caucasian subjects, in contrast to the situation with Indian populations (Saranath et al., 1991). PMID- 8353053 TI - A meta-analysis of studies of dietary fat and breast cancer risk. AB - There is strong evidence that breast cancer risk is influenced by environmental factors, and animal experiments and human ecological data suggest that increased dietary fat intake increases the incidence of the disease. Epidemiological evidence on the relationship of dietary fat to breast cancer from cohort and case control studies has however been inconsistent. To examine the available evidence we have carried out a meta-analysis to summarise quantitatively the large published literature on dietary fat in the aetiology of breast cancer. After assembling all of the published case control and cohort studies, we extracted the relative risk in each study that compared the highest to the lowest level of intake. We then calculated a summary relative risk for all studies. The summary relative risk for the 23 studies that examined fat as a nutrient was 1.12 (95% CI 1.04-1.21). Cohort studies had a summary relative risk of 1.01 (95% CI 0.90-1.13) and case control studies a relative risk of 1.21 (95% CI 1.10-1.34). Summary estimates of risk for specific types of fat excluded unity for only saturated fat. For the 19 studies that examined food intake, the summary relative risks were 1.18 (95% CI 1.06-1.32) for meat, 1.17 (95% CI 1.04-1.31) for milk, and 1.17 (95% CI 1.02-1.36) for cheese. Summary relative risks for total fat intake were examined for several potential modifying factors. Regression analysis showed that European studies were more likely than studies done in other countries to show an increased relative risk associated with dietary fat and breast cancer, after taking into account potential modifying factors that included study design and quality. PMID- 8353054 TI - Expression of pepsinogen C in human breast tumours and correlation with clinicopathologic parameters. AB - We have examined by immunohistochemistry the ability of breast carcinomas to produce pepsinogen C, an aspartyl proteinase usually involved in the digestion of proteins in the stomach. A total of 113 out of 245 breast tumours (46%) were positive for pepsinogen C immunostaining. There was a significant association between pepsinogen C and oestrogen receptors with proteinase levels higher (HSCORE) in oestrogen receptor positive tumours than in oestrogen receptor negative. There was also a significant association between pepsinogen C and histological grade, pepsinogen C levels being higher in well and moderately differentiated breast carcinomas than in poorly differentiated tumours. On the basis of these results, we suggest that pepsinogen C may be useful as a marker of good prognosis in breast cancer. PMID- 8353055 TI - A phase II and pharmacokinetic study with oral piritrexim for metastatic breast cancer. AB - Piritrexim is a lipid-soluble antifolate which, like methotrexate, has a potent capacity to inhibit dihydrofolate reductase. We performed a multicentre phase II study with piritrexim in patients with locally advanced or metastatic breast cancer. Twenty-four patients of which sixteen had received prior chemotherapy, were initially treated with 25 mg piritrexim orally administered trice daily for four days, repeated weekly, with provision for dose escalation or reduction according to observed toxicity. Of twenty-one patients evaluable for tumour response, one patient achieved a partial response which lasted for 24 weeks. Three patients had stable disease during 12 weeks of treatment, seventeen had progressive disease. Pirtrexim was generally well tolerated, in eighteen patients the dose could be escalated. Myelotoxicity was the most frequent observed toxicity of this piritrexim regimen. Leucopenia and thrombocytopenia grade 3/4 occurred in 38% of the patients sometime during treatment. Pharmacokinetic analysis of piritrexim in three patients during the first treatment cycle, revealed peak levels 1 to 2 h after an oral dose, with a trend towards a higher peak plasma levels and AUCs on the fourth dosing day compared with the first dosing day. In conclusion, orally administered piritrexim appears to be a regimen with little activity in patients with locally advanced or metastatic breast carcinoma. PMID- 8353056 TI - The relationship between students' behaviour at home and attention and achievement in elementary school. AB - In this study a model is proposed in which attention in the classroom is supposed to mediate the relationship between home background factors and achievement in school. Home background factors in the study were the socioeconomic status of the parents (SES) and the amount of problem behaviour of the child at home. The latter was supposed to be an indicator of the adequacy of parental discipline practices. For attention a distinction is made between a behavioural component termed attentional behaviour, and a cognitive component termed attention regulation. The effects of attention were studied for two domains of achievement, namely reading comprehension and arithmetic. The model was tested by means of structural equations modelling in a sample (N = 376) of 9-year-old children attending grade 6 of regular elementary schools in the Netherlands. The results showed that attention can be considered as an important mediator between home problem behaviour and achievement in school. The absence of problem behaviour at home had a substantial positive relationship with attention, the latter having moderate effects on arithmetic achievement and reading comprehension. No effects of SES on attention were found. Distinguishing between attentional behaviour and attention regulation, it appeared that the latter is equally related to both types of achievement. Interestingly, however, classroom attentional behaviour was more closely related to arithmetic achievement than to reading comprehension. Finally, SES appeared not to be related to arithmetic achievement but exerted a small direct effect on reading comprehension. PMID- 8353057 TI - Proximate causes of aggressive fighting in middle school children. AB - In study 1, 8- and 11-year-old girls and boys (N = 110) were interviewed individually and asked about why children in general, and themselves in particular, fight with fellow pupils in the playground. A substantial proportion of children (51 per cent) reported having had at least one aggressive fight during the previous year. The most common reasons for children resorting to fighting were retaliations to teasing, retaliations to unprovoked assaults, disagreements over aspects of the game that was being played, because another child was disliked, and to settle dominance disputes. In study 2, a direct observational methodology was employed to examine how often children of these ages engage in aggressive fighting, how long fights last, and their proximate causes. Among the younger pupils, a large proportion of fights (43.3 per cent) had no obvious immediate cause to an adult observer, but others were caused when a playful assault received an aggressive retaliation (15.4 per cent), and by disputes over space in the playground (13.5 per cent). Among the 11-year-old pupils, a smaller percentage of fights (14.8 per cent) had no obvious immediate cause. The two most common causes of fighting at this age were aggressive retaliations to teasing (25.9 per cent) and aggressive retaliations to accidental injury/hurt (18.5 per cent). In study 3, in situ interviews were combined with direct playground observations in order to reveal participants' views (or onlookers' views if participants were not available to be interviewed) about the causes of fights. Again, the most common causes of fighting were disputes over some aspect of the game being played (33.3 per cent), aggressive retaliations to teasing (25.0 per cent), disagreements over possession of toys/equipment (14.6 per cent), and aggressive retaliations to accidental injury/hurt (14.6 per cent). Age and sex differences are reported in some measures across all three studies. The results are discussed in terms of their implications for interventions aimed at improving children's experiences of life on the school playground. PMID- 8353058 TI - Using the child behaviour checklist in ordinary primary schools. AB - The study considers the application of the Child Behaviour Checklist (Achenbach & Edelbrock, 1986) to the identification of children with emotional and behavioural difficulties in ordinary primary schools. Teachers provided checklist data on a sample of 320 boys and 118 girls previously referred to the schools psychological services and a further 183 boys and 39 girls who had not been referred. There was a high level of agreement between referred and non-referred student status and subsequent classification using the CBCL criteria for psychiatric disturbance. An analysis of variance was carried out to determine how far teacher expectations may contribute to CBCL scores. The results indicated that teacher differences within schools are more important than the differences which exist between teachers working in different schools. The results support the validity of the CBCL. The future application of the CBCL in ordinary schools is discussed. PMID- 8353059 TI - Stress levels, gender and personality factors in teachers. AB - The study reports an investigation of stress levels, gender and personality dimensions in a sample of school teachers. The Professional Life Stress Scale (PLSS) was used to assess teachers' stress levels and the Eysenck Personality Questionnaire (EPQ) was used to define their personality dimensions (Extroversion Introversion, Neuroticism-High Psychoticism-Low Psychoticism). The study sample consisted of 95 teachers, 51 females and 44 males. Results revealed that the majority of teachers sampled, 72.6 per cent, were experiencing moderate levels of stress, and 23.2 per cent serious levels. T-test results showed no significant difference between male and female teachers in stress levels. Correlation analysis between stress level and personality dimensions revealed significant positive correlation between stress and psychoticism. A significant negative correlation emerged between stress and extroversion, and a significant positive correlation between stress and neuroticism. A multiple regression analysis revealed that extroversion and neuroticism were the best predictors of stress levels. Overall, the results therefore indicated that personality dimensions appear to contribute more to stress levels than do the variables of either age or gender. PMID- 8353060 TI - Teacher stress and cognitive style. AB - The aim of the study was to investigate the relationship between the teacher's cognitive style and occupational stress. A sample of 212 teachers in Maltese secondary schools completed a questionnaire surveying both the level of overall stress and the severity of four major areas of job stress. They were also given the Cognitive Styles Analysis which assesses two fundamental dimensions of cognitive style, wholist-analytic and verbal-imagery. For the top and bottom 25 per cent of the sample with extreme style characteristics, self-reported teacher stress was not related to style in a simple manner. However, style interacted significantly with teacher age. With regard to the four major areas of occupational stress, significant variations in the levels of stress were observed with style: whereas Analytics reported greater stress than Wholists for 'pupil misbehaviour' and 'poor working conditions', the converse was true for 'poor staff relations' and 'time pressures'. PMID- 8353061 TI - A developmental study of specific spelling disability. AB - Previous studies have identified a group of individuals with specific problems in spelling, and compared them to a group with problems in reading and spelling. Those who are poor at reading and spelling are thought to have more severe underlying language problems. This study compared the cognitive abilities of three groups of children: one specifically spelling disabled, one spelling and reading disabled, and one control group without reading or spelling problems. The groups were identified at age 14. A five-year retrospective analysis of their performance revealed that both of the disabled groups had been significantly poorer than the controls, not only in spelling but also in reading. Both the disabled groups showed other signs often associated with dyslexia such as poor WISC-R Coding and Digit Span. Analyses of their spelling errors did not reveal the superior phonetic abilities which some other studies have found to differentiate specifically spelling disabled from reading + spelling disabled groups. The specific spelling disabled group did show some evidence of superiority in Verbal IQ subtests. These results are consistent with the idea that specific spelling disability is a residual problem of individuals who, possibly by means of underlying verbal strengths, have managed to compensate for earlier reading difficulties. PMID- 8353062 TI - The effect of cognitive style and mode of presentation on learning performance. AB - The effect of text-plus-text versus text-plus-picture computer presentation conditions, and the students' cognitive styles, on learning performance was investigated. In the text-plus-text condition, the learning material content described the working of car braking systems. The text-plus-picture condition consisted of text with additional pictorial information. Fifty-nine 15-16-year old students in a secondary school were randomly assigned, within sexes, to one of the conditions. Having worked through the computer presented material, they were given a post-test overall learning performance. Immediately following this, they did the Cognitive Styles Analysis (CSA) (Riding, 1991) which measures an individual's position on two cognitive style dimensions; Verbal-Imagery and Wholist-Analytic. It was found that the Verbal-Imagery cognitive style and presentation condition interacted in their effect on overall learning performance (p < .05). In the text-plus-picture condition Imagers were superior to Verbalisers, while the text-plus-text condition Verbalisers did better than Imagers. It was also observed that Imagers used more diagrams to illustrate their answers than Verbalisers. The results are discussed in terms of their implications for instruction. PMID- 8353063 TI - Affective factors and learning behaviour in secondary school mathematics and English lessons for average and low attainers. AB - This study had two broad aims; firstly, to investigate the predictive relationships between i) overall subject affective factors (attitude and subjective norm), ii) specific lesson factors (behaviour intention, perceived preventive factors and self efficacy) and iii) learning behaviour during lessons; and secondly, to investigate the consistency of these affective factors across English and maths, and whether there were differences between average and low attaining pupils in these affective factors. Twenty-eight boys and girls, aged 11 14 years, in an inner city comprehensive school were assessed for these factors in two subjects over two occasions. It was found that neither attitude nor subjective norm were consistently predictive of intentions. The lesson specific factors (behaviour intention, preventive factors and self efficacy), which were inter-related, were moderately predicted by past learning behaviour, and were each predictive of subsequent learning behaviour. Pupils were also consistent in their affective perspectives to learning maths and English, though few differences were found between average and low attaining pupils. The significance of the findings is discussed in terms of the theoretical links between self efficacy and reasoned action approaches, the context of assessment and the nature of behaviour intention. PMID- 8353064 TI - Breast cancer: more clarity or more confusion? PMID- 8353065 TI - Euthanasia: more confusion than ever in The Netherlands. PMID- 8353066 TI - Battle over PCR fees. PMID- 8353067 TI - Immunosuppression with purine analogues--the flip side of the gold coin. PMID- 8353068 TI - The challenge of dose-intensity in ovarian cancer. PMID- 8353069 TI - Dose effect relationship in breast cancer. PMID- 8353070 TI - Drugs ten years later: epirubicin. PMID- 8353071 TI - Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia. AB - BACKGROUND: Fludarabine monophosphate is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) with response rates, including hematological complete remissions, of 50%-60% in previously treated and 75%-80% in previously untreated patients. PATIENTS AND METHODS: Here, the clinical experience with and side effects of fludarabine are reported in 19 patients with refractory CLL (17 B-CLL, 2 T-CLL). All patients were pretreated with one to four different regimens and had progressive disease. Fludarabine was administered at a dosage of 25 mg/m2 daily for 5 days as a 30-minute intravenous infusion. This course was repeated every fifth week. Dosage and time course were adapted to toxicity. RESULTS: 12/18 (67%) evaluable patients achieved partial remissions (PR), 1/18 (6%) had stable disease (SD) and 5/18 (28%) were progressive. The median duration of partial remission until relapse or death was 6 months. Most responses to fludarabine occurred within two treatment courses. Major toxic effects included infections in 11 patients and nausea in 8 (mainly grade 1). Meanwhile, three patients died of progressive disease and 8 of pneumonias or other infections. Two patients had pneumocystis carinii pneumonias and one an aspergillus pneumonia. The high infection rate may be due not only to hypogammaglobulinaemia or fludarabine-induced granulocytopenia but also to a remarkable decrease of CD4(+)-cells during fludarabine therapy. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. CONCLUSION: It is concluded that fludarabine is effective even in patients with advanced chronic lymphocytic leukemia refractory to multiple chemotherapy regimens. However, fludarabine has a remarkable suppressive effect on T-lymphocytes, predominantly CD4(+)-lymphocytes. Long-term antibiotic prophylaxis is recommended. PMID- 8353072 TI - A randomised dose intensity study in ovarian carcinoma comparing chemotherapy given at four week intervals for six cycles with half dose chemotherapy given for twelve cycles. AB - BACKGROUND: The importance of dose intensity has not been clearly defined in ovarian cancer and we present a prospectively randomised trial of dose intensity in patients with ovarian cancer. PATIENTS AND METHODS: Ninety-nine patients with FIGO stage Ic, II, III and IV epithelial ovarian cancer were randomised to receive cycles of standard dose cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with adriamycin (50 mg/m2) and ifosfamide (5 G/m2) for 6 cycles at monthly intervals (49 patients) or cycles of half dose cyclophosphamide (300 mg/m2) and carboplatin (150 mg/m2) alternating with adriamycin (25 mg/m2) and ifosfamide (2.5 G/m2) for 12 cycles at monthly intervals (50 patients). Patients in each arm were well balanced for major prognostic factors. RESULTS: The combined clinical response rate (complete response and partial response) on the 6 month arm was 76% compared with 48% on the low dose intensity arm (p = 0.009). With a median follow up of 25.7 months the median survival on the low dose intensity arm is 20.9 months. The median survival point on the 6 month arm has not yet been reached. The median progression free interval on the 12 month arm was 19.8 months, the median value has not yet been reached on the standard arm. The amount of residual tumour following initial laparotomy was the only significant independent variable affecting survival (p = 0.0001). The mean received dose intensity of each drug was greater than 80% of the planned dose intensity. More patients had clinical disease progression during treatment on the low dose intensity arm (42%) when compared to the standard dose intensity arm (8%) (p = 0.0003). Fifteen patients on the standard dose arm experienced a total of 18 delays and 5 patients on the low dose arm experienced 17 delays. Nausea, vomiting and diarrhoea were similar for both standard and low dose cycles of chemotherapy with a consequent benefit for patients receiving fewer cycles even though these were of higher dose. CONCLUSIONS: The combination studied was more effective when given at the higher dose intensity and the improved response and survival was not accompanied by a significant increase in toxicity. PMID- 8353073 TI - Patterns of survival in patients with Hodgkin's disease: long follow up in a single centre. AB - BACKGROUND: Prolonged remission can now be induced in the majority of patients with Hodgkin's disease with chemotherapy and/or irradiation. However, there is a significant proportion of patients in whom this approach fails, either at presentation or subsequently. Survival is the definitive endpoint to assess treatment efficacy. In this study, the survival patterns of a large group of consecutive patients treated in a single institution are presented. RESULTS: The overall median survival was 18.3 years. Clinical remission (complete remission plus good partial remission) was induced in 443 (85%); the median survival of patients in remission has not been reached. Fifty-eight patients achieved responses less than clinical remission with initial therapy (partial response) or had progressive disease, the median survival of this group being 1.4 years. With further therapy, remission was subsequently induced in 10; 5 are still alive, 5 have died between 1.9 years and 14.3 years. Twenty patients died before completion of therapy. Recurrence has been documented in 147 of the patients in remission (following initial therapy) over a median follow up period of 13 years (minimum 5 years). One hundred forty-three of these patients were retreated following recurrence (105 chemotherapy, 28 radiotherapy, 6 combined modality treatment and 4 surgery). Second remission was induced in 109/143 (76%). There was a trend towards better second remission induction in patients whose first remission was longer than 1 year (p = 0.06). The median duration of second remission was inferior to first remission duration (p < 0.001). There was no correlation between duration of first remission and survival following recurrence (p = 0.8) or with duration of second remission (p = 0.54). There was no significant difference in duration of second remission between patients who were initially treated with radiotherapy or chemotherapy (p = 0.3). The median survival following second remission was 12.0 years, being the same for patients with initially localized disease (stages I and II) treated with radiation alone and for patients with advanced Hodgkin's disease (stages III and IV) treated with chemotherapy. Survival after recurrence is significantly better for patients under 50 years at the time of recurrence (p < 0.001). Second recurrence was documented in 46 patients, third remission being reinduced in 22, the median survival of the latter being 5.1 years. CONCLUSION: These results illustrate the importance of prolonged follow up in defining the clinical course of patients with HD and are vital for planning experimental chemotherapy at the time of treatment failure or recurrence. PMID- 8353074 TI - Blood lymphocyte clonal excess in advanced non-Hodgkin's lymphoma. Relation to clinical data and prognosis. AB - BACKGROUND: Increasingly sensitive methods, based on the monoclonal nature of NHL, are used to detect tumour spread and remaining disease. Since the lymphomas are thought to arise due to successive genetic changes, clonal cells in different compartments do not necessarily represent the same disease despite a common clonal origin. PATIENTS AND METHODS: In 179 patients with advanced NHL, clonal cells in peripheral blood were identified by light chain restriction analysed in flow cytometry, i.e. clonal excess (CE) analysis. RESULTS: CE was more common in low grade NHL (52%) than in high grade NHL (21%). In patients with a normal lymphocyte count CE was found in 23%. CE was significantly correlated to small cell histology and bone marrow involvement. In high grade NHL CE in peripheral blood was more common in those with discordant small or mixed cell involvement of the bone marrow. CE was significantly related to failure to achieve remission in both histologic subgroups. Survival was not influenced by CE in low grade NHL but in high grade NHL. In multivariate analyses however, CE did not emerge as an independent risk factor but age, B-symptoms and LDH were the major factors. CONCLUSIONS: The utility of blood CE analyses in clinical praxis has still to be settled and the prognostic value of CE per se seem limited in the current perspective. The existence of CE in high grade NHL might be a clue of different biology as compared to de novo high grade NHL. PMID- 8353075 TI - Escalated M-VAC chemotherapy and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in patients with advanced urothelial tract tumors. AB - BACKGROUND: The M-VAC regimen (methotrexate, vinblastine, adriamycin, and cisplatin) has significant antitumor activity in patients with advanced urothelial tract cancer. Growth factors may provide the possibility of treating patients with higher doses of chemotherapy, for longer periods, with less morbidity, and improved results. A trial of an escalated dosage of M-VAC with recombinant GM-CSF (rhGM-CSF) was initiated. PATIENTS AND METHODS: 23 patients were treated with an escalated dose of M-VAC every 2 weeks plus rhGM-CSF 250 micrograms/m2 s.c. days 4-10. Dose level I (n = 13) was 1.65 times the dose of standard M-VAC. Adriamycin and cisplatin were given at 2.5 times the dose of standard M-VAC. Dose level II (n = 10) was a relative dose intensity of 1.95. Adriamycin and cisplatin were both given at 2.9 times the dose. CONCLUSIONS: The response rate was 70% (95% CI 60%-80%). Seven patients (30%) had CR, and 9 (39%) had a PR. Five (22%) patients had stable disease and 2 (9%) had progression. Of the CR patients, 3 had the CR confirmed pathologically (CRp). Response occurred in 11 patients treated at dose level I and 5 at dose level II. Toxicity was primarily hematologic. Dose level II was too toxic due to thrombocytopenia. Non hematologic toxicity was minimal. The value of this schedule (dose level I) compared to standard M-VAC will be further evaluated in a randomized trial to be initiated by the Genitourinary Group of the EORTC. PMID- 8353076 TI - Phase II study of an oral combination of doxifluridine, prednimustine and idarubicin (FUPRIDA) for first line treatment of advanced breast cancer. AB - BACKGROUND: An oral combination chemotherapy for breast cancer may be of advantage for many patients, if its activity is equivalent to that of i.v. treatments. The bioavailability of oral idarubicin and of oral doxifluridine allows for their use in an oral 3 drug regimen. PATIENTS AND METHODS: Idarubicin 29 mg/m2 was given on day 1, doxifluridine 1500 mg and prednimustine 60 mg were given daily for 10-14 days (7 days/m2) in 17 patients with advanced breast cancer. Cycles (1 to 18) were repeated every 4 weeks or delayed if required by toxic effects. RESULTS: Nine responses were observed with durations ranging from 2 to 16 months. Responding lesions were the primary tumor, or skin, liver and bone metastases. WHO grade 3-4 toxic effects included leukopenia (7 patients), diarrhea and emesis (2 and 1 patient). There were no toxic deaths. CONCLUSIONS: If our results are confirmed, this oral 3-drug-combination is a safe and effective treatment that may improve the quality of lives of breast cancer patients with poor venous access. PMID- 8353077 TI - Phase II study of sequential high-dose methotrexate (MTX) and 5-fluorouracil (F) alternated with epirubicin (E) and cisplatin (P) [FEMTX-P] in advanced gastric cancer. AB - BACKGROUND: FAMTX (5-fluorouracil, adriamycin, methotrexate) is one of the most effective drug combinations in gastric cancer. Therefore, modifications of FAMTX appear of interest and the FEMTX-P regiment was conceived. PATIENTS AND METHODS: Fifty patients with unresectable locally advanced and/or metastatic gastric carcinoma were treated with methotrexate 1500 mg/m2 i.v. and 5-fluorouracil 1500 mg/m2 i.v. on day 1; leucovorin rescue 15 mg/m2 orally every 6 hours for 8 doses on days 2 and 3; epirubicin 60 mg/m2 i.v. and cisplatin 50 mg/m2 i.v. on day 15, q 4 weeks. RESULTS: Of forty-seven patients evaluable for response, five (11%) achieved complete responses and seventeen (36%) partial responses (total response rate 47%). The median duration of response was 8+ months (range: 5-25+ months). Four of 14 patients with locally advanced disease were successfully downstaged and subsequently resected. The median duration of survival of all patients was 10 months (range: 1-25+ months). Leukopenia grade 4 occurred in 18% of patients and thrombocytopenia grade 4 and mucositis grade 4 in 4% and 2%, respectively. Treatment postponement for hematologic toxicity was necessary in 54% of patients. CONCLUSIONS: The FEMTX-P regimen is an active regimen in advanced gastric carcinoma, with acceptable toxicity. PMID- 8353078 TI - Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide (ADOC) in invasive thymomas: results in six patients. AB - BACKGROUND: Locally advanced malignant thymomas are usually radically resectable in about 60% of stage III but hardly ever in stage IVA. Neoadjuvant chemotherapy followed by surgery could improve both resection rate and curability. Cisplatin containing regimens have repeatedly been found to be highly active in advanced disease, with overall response rates ranging from 80%-90%. PATIENTS AND METHODS: 3 patients with stage III and 3 with stage IVA invasive thymomas, according to Masaoka staging, entered the study. Histology was: lymphoepithelial 4 cases, epithelial 2 cases. 4 cycles of the ADOC scheme--Adriamycin (40 mg/sqm), cisplatin (50 mg/sqm) on day 1, vincristine (0.6 mg/sqm) on day 2, and cyclophosphamide (700 mg/sqm) on day 3, every 21 days--were administered to 5 patients, while 1 patient received 5 cycles. RESULTS: 5/6 patients (83.3%) attained partial responses and underwent radical surgery followed by two further ADOC cycles. The disease-free intervals were 5+, 6+, 15+, 16+, 26+ months. One patient showing stable disease at the end of the fifth cycle was referred to radiotherapy. Toxicity was tolerable: grade III (WHO) nausea/vomiting and leukopenia grade III occurred in 2 patients each. CONCLUSIONS: These results suggest that the ADOC scheme is active as a neoadjuvant approach in invasive thymoma stages III and IVA, rendering possible radical resectability in 83% of patients. PMID- 8353079 TI - Myocardial infarction after chemotherapy for testicular teratoma. PMID- 8353080 TI - Severe hypocalcaemia after treatment with oral clodronate and aminoglycoside. PMID- 8353082 TI - San Salvatore Prize coupled with Kaplan Lecture goes to Gianni Bonadonna. PMID- 8353081 TI - Should we be using 5-HT3 antagonists as first line antiemetic therapy in cisplatin-based chemotherapy? PMID- 8353083 TI - Antiemetic therapy--where do we go from here? PMID- 8353084 TI - Euthanasia in The Netherlands: facts and moral arguments. AB - Some facts about euthanasia practices in The Netherlands are given. It is shown that there are several possible courses of action at the end of life, of which active euthanasia is the most problematic. Euthanasia is related to respect for the patient and the patient's right to refuse medical treatment. Some moral arguments against and in favour of euthanasia are discussed. PMID- 8353085 TI - The relevance of pharmacology in clinical oncology practice. Pharmacology is relevant. PMID- 8353086 TI - The relevance of pharmacology in clinical oncology practice. Pharmacology is (as yet) no relevant.... PMID- 8353087 TI - The relevance of pharmacology in clinical oncology practice. The moderator thinks that.... PMID- 8353088 TI - Hematopoietic growth factors and chemoprotectants: should we move toward a two step process for phase I clinical trials in oncology? PMID- 8353089 TI - Oral ondansetron in the prophylaxis of nausea and vomiting induced by cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in women with breast cancer. Results of a prospective, randomized, double-blind, placebo-controlled study. AB - BACKGROUND: The combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a widely used chemotherapy regimen in breast cancer patients. However, the control of nausea and vomiting induced by oral CMF is a rarely examined problem. Therefore we felt a randomized, placebo controlled study justified in order to improve currently available antiemetic therapy. SUBJECTS AND METHODS: In a randomised double-blind trial ondansetron given orally, 8 mg three times a day for 15 days, was compared with placebo in 82 breast cancer patients receiving chemotherapy with CMF (cyclophosphamide 100 mg/m2 orally days 1-14, methotrexate 40 mg/m2 i.v. days 1 and 8 and 5-fluorouracil 600 mg/m2 i.v. days 1 and 8). The patients recorded nausea and the number of vomits and retches daily on diary cards. Forty-two patients received ondansetron and 40 received placebo. RESULTS: Significantly more patients who received ondansetron experienced neither vomiting nor retching (emesis) compared to those receiving placebo over a 15 day treatment period (60% vs. 35%, p = 0.027). The difference, with 95% confidence limits, was estimated at 25 (4.45%). Furthermore, there was a trend in favour of ondansetron in the control of nausea. Ondansetron was well tolerated, with 25 patients (59%) reporting at least 1 adverse event compared to 18 patients (45%) receiving placebo (p = 0.191). CONCLUSION: The results indicate that ondansetron given orally for 15 days is safe and effective in the control of emesis induced by CMF. It is however too early to recommend ondansetron as standard antiemetic therapy for oral CMF, as the treatment of nausea and vomiting in this setting has not been studied thoroughly enough. PMID- 8353090 TI - Early clinical trial of MDL 73.147 EF: a new 5-HT3-receptors antagonist for the prevention of chemotherapy-induced nausea and vomiting. AB - BACKGROUND: Like MDL 72.222, one of the first selective 5-hydroxytryptamine3 (5 HT3) receptors antagonist discovered, MDL 73.147 EF has been shown to possess antiemetic properties in the ferret model. We conducted a phase I study with MDL 73.147 EF in 31 patients, treated with emetogenic drugs over one to five days (cisplatin, cyclophosphamide, doxorubicin, dacarbazine). PATIENTS AND METHODS: 5 groups of at least 5 patients received rising unit doses of MDL 73.147 EF (10 to 50 mg) intravenously before chemotherapy, with two more doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting recorded by an independent observer. RESULTS: 51.6% of the patients were complete responders on day one and 40% on days two to five. One patient was given other rescue antiemetic therapy. Adverse events included constipation (25.8%), mildly elevated blood pressure (12.9%) and other minor events. No extrapyramidal effects have been reported. There was no suggestion of dose-dependent efficacy at the dose levels studied in this limited set of patients. CONCLUSIONS: We conclude that MDL 73.147 EF is a well tolerated and possibly effective antiemetic. PMID- 8353091 TI - A phase II study of ifosfamide, carboplatin and cisplatin in advanced and recurrent squamous cell carcinoma of the uterine cervix. AB - BACKGROUND: Discouraging response duration and long-time survivals have so far been the result of cisplatin-containing combination chemotherapy against advanced or recurrent squamous cell carcinoma of the uterine cervix. In order to increase the platinum-based effect upon this tumor without an increase in the specific toxicity of cisplatin, we combined it with carboplatin, added ifosfamide, which has been shown to possess a comparable degree of single-agent activity. PATIENTS AND METHODS: Thirty-six patients with advanced or recurrent squamous cell carcinoma of the uterine cervix not curable by radiation or surgery were treated with a combination of ifosfamide 1.5 gr/m2 i.v. days 1-3, carboplatin 200 mg/m2 i.v. day 1, and cisplatin 50 mg/m2. Thirty-one patients were evaluable for response and 34 patients for toxicity. RESULTS: Twenty-three patients responded (64%), 11 (31%) of them completely, and 12 (33%) partially. Median response duration was 23 weeks (range 8-107 weeks), reaching 27 weeks and 21 weeks for patients with and without disease in previously irradiated areas, respectively. Median survival is 40 weeks (range 1-114 weeks). Toxicity consisted mainly of moderate to severe myelosuppression, resulting in 2 toxic deaths. CONCLUSION: The response rate, also for earlier irradiated areas, compares favorably with other known cisplatin-containing regimens. The combination deserves investigation in a randomized setting. PMID- 8353092 TI - Fats used in seasoning and breast cancer risk: a case-control study in Moscow, Russia. AB - BACKGROUND: As part of a case-control study of breast cancer conducted in Moscow the relationship between consumption of fat in seasoning and risk of breast cancer was assessed. DESIGN: The study comprised 92 cases and 110 controls. Cases were newly diagnosed consecutive cases seen at the breast clinic of the Cancer Research Centre of the Russian Academy of Medical Sciences during the year 1990. None of the patients had been previously treated for breast or other cancers and none had distant metastases. Patient were interviewed in the Clinic within two days of admission. Controls were recruited from women visiting their friends and relatives treated in the same Cancer Centre. RESULTS: Four levels of frequency of use of butter and vegetable oils, and four levels for combined sources were created to evaluate the association between use of fat in seasoning and breast cancer risk. Compared to low use, a non-significant increase in risk was observed for the highest intake of butter (Odds Ratio (OR) = 1.5, 95% Confidence Interval (CI) (0.8, 3.0)). High frequency of use of vegetable oil in seasoning decreased the risk of breast cancer. For the highest category of use, the adjusted OR was 0.2 (95% CI (0.1, 0.5)). Frequent use of mayonnaise also appeared to be associated with a decrease in the risk of breast cancer (OR = 0.1; 95% CI (0.01, 0.4)). For total fat seasoning consumption (vegetable oil+mayonnaise), the adjusted OR for highest category of intake was 0.1 (95% CI (0.03, 0.3)). CONCLUSIONS: The results of the study suggest a negative association between consumption of fat used for seasoning (except butter) and breast cancer risk. This may be a direct effect or due to increased consumption of salad-type vegetables by high consumers of these sources of fats. The topic should be addressed in other studies in different populations. PMID- 8353093 TI - High grade soft tissue sarcoma. AB - The management of our patient was similar to that of many patients with soft tissue sarcomas. His primary care was in a General Hospital where the surgeon had no specialist experience of these tumours and did not anticipate such a diagnosis. As a result the diagnostic procedure was inappropriate and compromised the chances of success of further more radical conservative surgery. Radiotherapy was unable to prevent local recurrence and amputation became necessary. Pulmonary metastases developed and were resected but within a short space of time extensive inoperable metastases recurred. Although these responded to chemotherapy, the response duration was short and the patient died soon afterwards. The major lessons to be learned are the need to have a high index of suspicion about a possible neoplastic cause of increasing soft tissue swellings and to refer patients for biopsy to a specialist centre where there is experience of all aspects of the management of these rare but potentially curable malignancies. PMID- 8353094 TI - Pharmacokinetics of 5-fluorouracil in colorectal cancer patients receiving interferon. AB - BACKGROUND: The outlook for patients with advanced colorectal cancer remains poor. Recent reports of the combination of 5-fluorouracil (5-FU) and alpha interferon in colorectal cancer have suggested better response rates. One possible explanation for interaction between 5-FU and interferon is that interferon alters the pharmacokinetics of 5-FU, increasing plasma 5-FU levels. PATIENTS AND METHODS: To investigate the possibility of interaction between the two agents, steady state 5-FU pharmacokinetics was evaluated in patients with colorectal cancer who received 5-FU by continuous i.v. infusion with and without concurrent administration of subcutaneous alpha-interferon. 5-FU levels were measured by reverse-phase high-performance liquid chromatography. RESULTS: Twenty six patients were evaluated. There were 4 partial responses (15%). There was no significant difference in steady state 5-FU levels whether or not alpha interferon was administered concurrently. CONCLUSION: Any synergistic activity that may exist between this combination of 5-FU and alpha-interferon is not simply due to altered 5-FU pharmacokinetics. PMID- 8353095 TI - Low-dose oral etoposide in epithelial cancer of the ovary. AB - AIMS: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of low-dose oral etoposide (E) in patients (pts) with epithelial cancer of the ovary previously treated with cisplatin. PATIENTS AND METHODS: Eighteen pts receiving 50 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 microgram/ml) with evaluation during the first cycle of bioavailability and weekly 24-hour drug concentrations. RESULTS: Among 17 evaluable pts, 1 partial remission of 9 months. Dose-limiting neutropenia of high inter-patient variability. Mean bioavailability value of 75%, ranging from 44% to 100%. No correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC during the first cycle. CONCLUSIONS: Low dose oral E is ineffective as salvage treatment in epithelial cancer of the ovary. The large variability of neutropenia requires a careful hematological monitoring to avoid severe myelosuppression. PMID- 8353096 TI - Assessing quality of life in clinical trials. PMID- 8353097 TI - Secondary cancer following Hodgkin's disease. PMID- 8353098 TI - Renal cancer after busulphan treatment for chronic myeloid leukemia: therapeutic implications. PMID- 8353099 TI - Pharmacokinetics and in vitro studies of l-leucovorin. Comparison with the d and d,l-leucovorin. AB - BACKGROUND: The active isomer of leucovorin (LV), LV-6S was compared with the racemic form, LV-6R,S and the inactive form, LV-6R. MATERIALS AND METHODS: Pharmacokinetic studies of LV-6S and 6R,S were performed on normal volunteers and patients. Growth of Pediococcus Cerevisiae (PC), a LV-dependent strain, was measured with the 3 forms of LV. CCRF-CEM, a leukemic human cell line, was used to compare the effect of LV-6S, 6R,S and 6R on the rescue of methotrexate (MTX) and on the cytotoxicity of 5-fluorouracil (5-FU). RESULTS: LV-6S exhibits pharmacokinetic patterns similar to those obtained with LV-6R,S whatever the route used, oral or intravenous. The growth of PC was similar with the active isomer and the racemic form while the unnatural isomer, LV-6R did not promote any growth. Cells exposed to MTX (10(-7) to 10(-5) M) were rescued from MTX cytotoxicity with LV-6S and LV-6R,S at concentrations 100 and 200 fold higher, whereas LV-6R did not reverse toxic effects of MTX. An enhancement of the cytotoxicity induced by 5-FU (10(-4) M) was obtained after preexposure of cells to LV-6S or LV-6R,S while LV-6R did not exhibit any synergistic effect. CONCLUSION: LV-6S has similar effects to LV-6R,S in vitro and in vivo but at half doses; its clinical use prevents the possible interference of the inactive isomer, especially in patients receiving high doses of LV. PMID- 8353100 TI - What can we learn from a meta-analysis of trials testing the modulation of 5-FU by leucovorin? Advanced Colorectal Meta-analysis Project. AB - BACKGROUND AND DESIGN: We previously reported a meta-analysis of all randomized clinical trials comparing 5-FU to 5-FU plus intravenous d.l. leucovorin (LV) in patients with advanced colorectal cancer. RESULTS: The meta-analysis confirmed the advantage of 5-FU/LV over 5-FU alone in terms of response rate: overall, the response rate was 11% with 5-FU alone vs 23% with 5-FU/LV (p < 10(-7)). At the same time, it was showed that tumor regression can not be considered a surrogate end point for survival in patients with advanced colorectal cancer: no significant survival advantage was observed for patients allocated to 5-FU/LV. The present paper focuses on the interest of meta-analysis to study the role of the biomodulation of 5-FU by LV. This approach is compared with the analysis of individual clinical trials in terms of power, bias and credibility. It is argued that for the meta-analysis to be reliable, individual patient data from all available studies must be used, rather than summary data extracted from published papers. CONCLUSION: It is concluded that meta-analysis is very useful as a tool to explore and summarize available data on a given clinical problem, though its purpose is not to recommend any treatment modality. This meta-analysis has confirmed both the benefit of biomodulation of 5-FU by LV, and the limitations of the current modalities to impact significantly on overall patient survival. Further laboratory and clinical research is warranted on the biomodulation of 5 FU by LV. PMID- 8353101 TI - Large scale trial for adjuvant treatment in high risk resected colorectal cancers. Rationale to test the combination of loco-regional and systemic chemotherapy and to compare l-leucovorin + 5-FU to levamisole + 5-FU. AB - BACKGROUND: Failure rate of colorectal cancer after surgical resection remains around 50% and adjuvant treatments are clearly required. PATIENTS AND METHODS: All patients with serosal involvement and/or lymph node metastases are at risk of recurrence (Dukes-Astler Coller B2, C1, C2). For thirty years many randomized trials testing chemotherapy and radiation therapy (rectum) have been conducted and some have demonstrated some kind of significant activity. We have analysed these trials and proposed with the EORTC GI tract cooperative group a new prospective randomized trial (40911). RESULTS: In colon cancer, five trials have tested single agent systemic chemotherapy and failed to demonstrated a significant increase in survival. Four trials have tested systemic chemotherapy with 5-FU + MeCCNU +/- oncovin and only one (NSABP COI ant ROI) has demonstrated some significant benefit in term of survival. The combination of 5-FU + levamisole has been tested in 4 trials; in two there was a trend in favor of the treated group and in the intergroup trial there was a very significant increase in survival for Duke C patients. Six trials have tested the efficacy of post operative local chemotherapy (intraportal); 3 demonstrated a significant increased survival and 2 a decrease in hepatic recurrence rate. Among the ongoing trials the EORTC 40911 aims to evaluate the interest of combining systemic chemotherapy (5-FU + levamisole or 5-FU + 1 folinic acid) to postoperative local chemotherapy (intraportal or intraperitoneal). In rectal cancer, preoperative radiation therapy significantly decreases the local recurrence rate, more than post-operative radiation therapy. The combination of post-operative radiation therapy with chemotherapy increases significantly survival rate. Presently patients with mobile rectal tumor located at the middle or the upper part of the rectum should be when possible randomized in trials such as the EORTC 40911. Concerning patients with large tumor located at the inferior part of the rectum new trials combining preoperative radiotherapy chemotherapy will be initiated. CONCLUSIONS: Some randomized trials using polychemotherapy have resulted in increasing survival rate in adjuvant setting regarding patients with colorectal cancer. New trials have been initiated to further improve these encouraging results. PMID- 8353102 TI - 5-Fluorouracil combined with the [6S]-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma. A phase I-II study of two consecutive regimens. AB - BACKGROUND: Potentiation of the antitumor activity of 5-fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase (TS), fluorodeoxyuridylate (FdUMP), and methylene tetrahydrofolate (5,10-CH2-FH4), which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C6 carbon of the pteridine ring. Only the levorotatory [6S]-folinic acid is transformed into active folate cofactors. However, the [6R]-stereoisomer is not inert; it was shown to interfere with the [6S] form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out 2 consecutive phase I-II studies of 5-FU combined with the [6S]-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. PATIENTS AND METHODS: Treatment comprised 5-FU by i.v. infusion for 2 hours (the initial dose was 350 mg/m2/d; it was incremented by 25 mg/m2/d until a maximal dose of 550 mg/m2/d) and [6S]-folinic acid (100 mg/m2/d by rapid i.v. injection in Regimen 1, and 100 mg/m2 by rapid i.v. injection followed by a 2-hour infusion of 250 mg/m2 in Regimen 2) for 5 days, every 21 days. Twenty-five pts and 27 pts were assessed in Regimen 1 and in Regimen 2, respectively. They had had no prior chemotherapy. The median follow-up time was 9 months and 15.5 months for patients treated with Regimen 1 and Regimen 2, respectively. For pts treated with Regimen 1, the response rate was 52% (CR, 12%; PR, 40%). The median time to disease progression was 9.2 months. The probability of survival at 12 months was 73%. For pts treated with Regimen 2, the response rate was 37% (CR, 7%; PR, 30%). The median time to disease progression was 8.9 months. The probability of survival at 12 months was 67%. Improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects (WHO grades > or = 3) were diarrhea, dermatitis, and mucositis. One single episode of grade 4 diarrhea occurred. After injection according to the schema in Regimen 1, [6S]-folinic acid was rapidly cleared from plasma (mean t 1/2 alpha and t 1/2 beta of 7.2 and 126 minutes, respectively). The mean concentration of the [6S]-stereoisomer two hours after injection was 5.8 mmol/L. After a rapid i.v. injection of 100 mg/m2 followed by a 2-hour infusion of 250 mg/m2, the mean concentration of [6S] folinic acid two hours after the injection was 57.5 mmol/L. Pharmacokinetic data suggests saturation of the metabolic conversion of [6S]-folinic acid when large doses are administered. CONCLUSION: The [6S]-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. However, increase of the daily dose of the folate did not result in a therapeutic improvement. The present results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines. PMID- 8353103 TI - L-folinic acid and 5-fluorouracil in the treatment of advanced breast cancer: a phase II study. AB - BACKGROUND: The combination of 5-fluorouracil (5-FU) and folinic acid (FA) is an active combination for the treatment of advanced breast cancer (ABC). Theoretically, the biologically active isomer of FA, 1-FA, should be more effective than racemic FA in modulating 5-FU activity. PATIENTS AND METHODS: Thirty-three patients (pts) with ABC, all previously treated with an anthracycline-based combination for advanced disease were treated with 1-FA: 100 mg/m2 i.v. and 5-FU: 370 mg/m2 i.v. for 5 consecutive days every 4 weeks. RESULTS: Three complete remission (CR) and 11 partial remission (PR) were obtained for an overall response rate of 42% (95% CI = 25-59). Median duration of response was 10 months, median survival was 15 months for responders, 11 months for NC and 3 for PD. Eleven pts experienced a WHO grade III-IV oral mucositis (33%), 6 pts had grade III and one grade IV diarrhea, two pts had grade IV neutropenia resulting in one toxic death. CONCLUSIONS: In this heavily pretreated population of pts with ABC, this regimen showed an interesting activity with substantial toxicity. Both the response rate and the pattern of side-effects seem similar to those experienced with the racemic mixture of d,1-FA. Modulated 5-FU warrants an increasing consideration in the treatment of breast cancer. PMID- 8353104 TI - Stereoisomers in clinical oncology: why it is important to know what the right and left hands are doing. AB - BACKGROUND: In the past few years it has become clear that the individual stereoisomers, especially the enantiomers, of a biologically active chiral molecule may differ in potency, pharmacological action, metabolism, toxicity, plasma disposition and urine excretion kinetics. The situation exists in all classes of therapeutically active agents including chiral agents used in clinical oncology. Chiral anticancer agents which exist as a pair of enantiomers are commonly administered as racemic (50:50) mixtures of the two isomers. The possibility exists that only one of the enantiomers possesses the desired pharmacological activity while the other is responsible for part or all of the observed toxicity. The toxicity due to the non-efficacious isomer may be the difference between a clinically useful anticancer drug and one which is too toxic to use. RESULTS: The chiral compounds used in standard and experimental cancer chemotherapy include leucovorin, ifosfamide and verapamil. Only one stereoisomer of leucovorin, (6S)-leucovorin is active and data suggests that the administration of just the single isomer may enhance the activity of the agent as well as improve therapeutic monitoring. Both enantiomers of verapamil, (R) verapamil and (S)-verapamil, are active in reversing adriamycin resistance in some tumor lines. The standard clinical formulation of verapamil is a mixture of the two isomers and cannot be used in clinical treatment of resistant disease due to the cardiotoxicity of the (S)-isomer. (S)-verapamil is the active calcium channel blocking agent while (R)-verapamil has no effect in this area. Thus, an effective anticancer drug would be (R)-verapamil. Data also exists which suggests that the use of a single isomer of ifosfamide may reduce dose limiting CNS toxicity. CONCLUSION: The existence of stereoisomeric forms of a chemical has been a recognized fact for almost 150 years. However, the clinical consequences of symmetry and asymmetry are only just beginning to be considered. Within the three-dimensional structures of the human body lie tremendous potentials for differential drug actions and, perhaps, new keys to the treatment of cancer and other diseases. The next few years should see the end to the two-dimensional clinical pharmacology we are accustomed to and the growth of stereochemical clinical pharmacology; where we always know what the right and left hands are doing. PMID- 8353105 TI - The patient as sufferer. AB - The use of the term sufferer to replace patient has become increasingly common. This paper examines the varied meanings implicit in the word sufferer from the Judaeo-Christian perspective. This includes the biblical themes of suffering as human nature, as punishment, as a test, as atonement and as liberation and deliverance. The consequences of these themes for the sufferer's role are examined, particularly the sufferer as accepting and the sufferer as victim. It is argued that replacing the medical model, implied by 'patient' with a theological model, implied by 'sufferer' does not free the person from the constraints of a damaging label. PMID- 8353107 TI - Cognitive therapy for depression with individuals with intellectual disabilities. AB - The increase in research into psychopathology in people with intellectual disability has recently spread to include depression. Several reports have appeared on the assessment of depression in the client group and there is a pressing need for research into treatment of depression in people with intellectual disability. The present paper reviews cognitive behaviour therapy for depression and reports on its adaptation for people with intellectual disability. Two case studies of individuals with mild intellectual disability illustrate the clinical applications. All the elements of cognitive behaviour therapy for depression were maintained and simplified. Both subjects were able to monitor their feelings of depression and subject 2 monitored the frequency of suicidal thoughts. Improvements were seen in both cases on the Zung Depression Inventory and daily monitoring of depressive feelings. PMID- 8353106 TI - Measuring medical students' empathy skills. AB - Empathy is an important skill for the medical practitioner or medical students to develop when interviewing patients. It helps the interviewer establish effective communication, which is important for accurate diagnosis and patient management. Two facets of medical education limit students' development of accurate empathy: the traditional format of interviewing training and the social ethos of medical training and medical practice, which stress clinical detachment. A number of researchers and educators have developed consulting skills training programmes, designed to enhance students' empathic skills and ability. One difficulty for researchers has been the conceptual complexity of the term 'empathy' and greater difficulty in measuring the dimension. This paper reviews the range of approaches to the measurement of empathy and reports on a research study designed to evaluate a two-stage measurement technique, involving a pencil-and-paper test of empathy and independent observer ratings of medical students' actual interview behaviours. Results lead to the conclusion that pencil-and-paper tests of empathy cannot incorporate the range of complex cognitive, emotional and behavioural components of the empathy construct. On the other hand, trained observers have been able to use items on a specially developed History-taking Rating Scale to discriminate between the empathic behaviours of a group of students trained in consulting skills with those of a group of control students who each carried out videotaped history-taking interviews with hospitalized patients. PMID- 8353108 TI - Coping strategies in major depressed, agoraphobic and comorbid in-patients: a longitudinal study. AB - The first aim of this study was to explore the diagnostic specificity of coping styles by comparing ways of coping in non-anxious major depressed, non-depressed agoraphobic, and both major depressed and agoraphobic (comorbid) in-patients. The second aim was to investigate whether a vulnerability model, a state model, or a combined vulnerability-state model of coping accounted best for the data. On admission and when discharged, 95 patients completed the Way of Coping Checklist and were evaluated on several symptom scales. Self-report symptom scales were completed at one-year follow-up as well. The 'purely' agoraphobic and the comorbid patients showed less seeking of social support and more wishful thinking than the major depressed patients. For the wishful thinking scale, these differences were related to differences in level of global psychopathology. Overall, the results for the seeking social support scale were consistent with a combined vulnerability-state model. The problem-focused coping and wishful thinking scores behaved mostly as state phenomena. The avoidance scores provided ambiguous evidence. In a subsample of 30 agoraphobic patients who received a combination of exposure and psychodynamic treatment, higher pre-treatment levels of seeking social support and lower pre-treatment levels of avoidance as coping both predicted a more favourable course of symptoms pertaining to fear of fear in the one-year follow-up period. PMID- 8353109 TI - The California Psychotherapy Alliance Scales: a pilot study of dimensions and elements. AB - The reliability and clinical utility of the rater form of the California Psychotherapy Alliance Scales (CALPAS-R) was investigated on a sample of 12 one hour audiotapes representing differing therapeutic dyads and sampled from sessions two to six of a relationship-oriented (exploratory) therapy within pilot cases of a large outcome study. Both global dimensions and element-based ratings were used to test the feasibility of employing the elements as a way of obtaining a finer-grained analysis of the therapeutic alliance. Results are reported in terms of the interrater reliability of the dimensions and elements, and show element ratings to yield dimensional measures similar or superior to global ratings in reliability. In addition, CALPAS-R ratings were analysed in conjunction with client ratings of session depth and smoothness as well as helpfulness. PMID- 8353110 TI - The assessment of antenatal emotional attachment: development of a questionnaire instrument. AB - The nature of the relationship which female and male expectant parents develop during pregnancy with their unborn baby has both theoretical and clinical significance. It potentially provides a framework for improved understanding of many aspects of psychosomatic obstetrics, including reactions to foetal loss. Existing instruments designed to assess this relationship inadequately differentiate between attitude to the foetus per se versus attitude to the pregnancy state or motherhood role. The present paper presents a theoretical model of the subjective experiences of human attachment. This is utilized to develop a questionnaire to assess the antenatal attachment construct. Item analysis results in a 19-item maternal and 16-item paternal questionnaire with high levels of internal consistency. Each takes approximately five minutes to complete. Finally, the factor structures of the resultant questionnaires are explored. PMID- 8353111 TI - Increased substance use in survivors of the Herald of Free Enterprise disaster. AB - Cross-sectional data are reported on 73 survivors of the Herald of Free Enterprise disaster. Many reported an increase in their consumption of alcohol, cigarettes, sleeping tablets, antidepressants and tranquillizers at six and 30 months. The level of increased use was, however, lower at 30 months than at six months, although this was less evident for alcohol and cigarettes than the other substances. In addition, self-reports of increased substance use are associated with higher levels of psychological distress as measured by the General Health Questionnaire and the Impact of Events Scale. It is suggested that substance use might help to maintain subsequent psychological distress. PMID- 8353112 TI - Peripheral victims of the Herald of Free Enterprise disaster. AB - We report on an unexpected phenomenon following the Herald of Free Enterprise disaster. A series of cross-channel ferry workers referred by their GPs to the Folkestone Mental Health Team, during the three years after the disaster, presented with post-traumatic stress disorder, despite having no direct contact with the disaster as survivors, bereaved relatives or helpers. A retrospective case study is described of 14 ferry crew members presenting with PTSD. Thirteen completed the GHQ60. Evidence is presented of severe functional impairment in this group. It is argued that these subjects are indirect victims of the Herald of Free Enterprise disaster. Ways in which the 'ripples outward' of a major marine accident might extend to such peripheral victims are discussed. PMID- 8353113 TI - High-frequency ventilation in newborn lambs after intra-uterine creation of diaphragmatic hernia. AB - Infants with congenital diaphragmatic hernia (CDH) die, because their lungs are hypoplastic and their pulmonary vascular resistance remains elevated after birth. In human newborns, it is difficult to appreciate the benefit of new therapeutic approaches, because the pathological findings are not uniform, the disease is rare and the clinical criteria for poor prognosis with conventional therapy are uncertain. To study the benefit of high-frequency ventilation (HFV) the use of Tolazoline in CDH, we created a diaphragmatic defect in sheep fetuses at 0.6 gestation and studied full-term newborns after a caesarian section. A sternotomy was performed to place catheters and flow probes on the aorta and pulmonary artery and to clamp the ductus arteriosus and the left pulmonary artery. Twins were used as control, and the CDH lambs were either ventilated with conventional ventilation (CV) or HFV. 23 ewes were operated upon with a 22% abortion rate and 31 newborn lambs (10 controls and 21 CDH) were studied. A complete gasometric and hemodynamic study was performed in 23 lambs (7 controls, 8 CDH with CV and 8 CDH with HFV). Clinical and pathological findings of the lambs with CDH were very similar to severe CDH in humans with bilateral lung hypoplasia, severe respiratory distress, high pulmonary vascular resistance and severe hypoxemia. HFV dramatically improved CO2 elimination, allowed less aggressive ventilation, and was associated with higher flows and lower systemic and pulmonary vascular resistance. However, HFV did not improve oxygenation leaving the newborn with severe hypoxemia associated with massive intrapulmonary foramen ovale shunting from right to left. PMID- 8353114 TI - Necrotizing enterocolitis (NEC)--mortality and long-term results. AB - From 1974-88 73 patients were treated for necrotizing enterocolitis (NEC) in the surgical department at the Children's Hospital of Cologne. 70% of these had other complaints and 77% were premature babies, of which 30% were small-for-dates. A greater than expected proportion of deaths occurred in babies not of low birth weight: Of those above 2500 g 35% died and of those under 1500 g 20%. Initial signs and symptoms became apparent in 80% within the first two weeks. The most frequent signs were distended abdomen (81%), diffuse tenderness (46%), bloody stools (39%) and absent peristalsis (39%). Radiology showed edema of the bowel wall in 49%, free air in the abdomen in 38% and intestinal pneumatosis in 34%. It remains questionable whether peritoneal lavage could lead to earlier diagnosis and referral of the sick children to the hospital. The course of the disease was less severe when babies had received breast milk. Colon and distal ileum were involved most frequently. Laparotomy showed perforations of the bowel in 39 patients (64%), inflammatory alterations in 18 and necroses in 12. The survival rates improved within the period of 1974-88 from 64 to 79%. Thirty-two of the 51 survivors were available for follow-up: 9 patients (28%) had more than 4 stools/day, 8 (25%) were underweight, 8 (25%) suffered from food intolerance, 5 (16%) from diarrhoea, 4 (13%) from limited exercise tolerance. Physical retardation could only be seen in 3 children under the age of 2. PMID- 8353115 TI - Early and semi-early surgery for scoliosis caused by hemivertebrae--indications and results. AB - We report a series of 50 congenital scolioses due to hemivertebrae. This malformation was responsible for progressive deformity, largely predominant on the frontal plane. The average follow-up was 5 years and 3 months. Seven patients had mature bones. The series comprised 31 girls and 19 boys. Three types of operations were performed: (a) hemivertebrae resection (5 cases); (b) early, most posterior convexity fusion carried out before the age of 6 years (26 cases), and (c) semi-early convexity fusion performed between the ages of 6 and 12 years (19 cases). The results obtained in children with a more than 2 years' follow-up were: (a) early convexity fusion (18 cases): 7 epiphyseodesis effects, 6 graft effects and 4 failures; (b) semi-early convexity fusion (16 cases): 6 epiphyseodesis effects, 8 graft effects and 2 failures; (c) hemivertebrae resection (5 cases): moderate gain that remained stable in 4/5 cases. PMID- 8353116 TI - Clinical course and treatment of pheochromocytomas in children. Analysis of five cases. AB - Between 1965 and 1990 five children with pheochromocytomas were treated. Clinical course, methods of diagnosis, treatment and results established by follow-up from 6 months to 20 years are presented. Hypertension and headaches occurred in all patients. One child with a malignant form of pheochromocytoma manifested central nervous symptoms imitating epilepsy and additionally diffuse pulmonary metastases were found. One patient had a family history of pheochromocytomas and presented with hypermetabolic state and neurovegetative symptoms. One child had multifocal tumors: two in the posterior mediastinum and one in the retroperitoneal space. All patients were treated by either enucleation of the tumor, tumor excision or adrenalectomy. One child died 12 years after surgery from the rapid progression of pulmonary metastases of pheochromoblastoma present at the time of diagnosis. PMID- 8353117 TI - Creation of experimental urethral obstruction in utero: evaluation of fetal renal function. AB - Management of obstructive uropathy diagnosed in utero would be markedly enhanced by the availability of a simple, safe and quantitative fetal renal function test to predict postnatal renal function. In order to allow experimental evaluation of such a parameter, we adjusted a model of complete urethral obstruction with urachal ligation in 30 fetal lambs at 79 or 99 days of gestation. The method described allows obstruction in male and female fetuses as early as 79 days of gestation, with an overall high survival rate (control: 12/14; obstructed: 23/29), although lower (6/12) when obstruction is performed early (79 days) during gestation. Consequences of obstruction were examined on the 121st day of gestation. Severe hydronephrosis, ureteral and calyceal dilatation, with or without ascites and pulmonary hypoplasia were observed in all fetuses; creatinine clearance determined in utero was decreased in both groups with obstruction (early and late) vs control group: 1.15 +/- 0.5, NS, and 0.58 +/- 0.4, p < 0.01 vs 1.61 +/- 0.8 ml/min/kg respectively. In both obstructed groups, fetuses with ascites displayed lower plasma creatinine concentration and higher creatinine clearance values when compared to fetuses without ascites. In conclusion, the experimental model of obstructive uropathy described appears efficient and easily reproducible, allowing therefore the evaluation of a predictive parameter of postnatal renal function. Our preliminary results suggest that renal fetal function is more dependent on the degree of obstruction than on the term of its creation. PMID- 8353118 TI - Use of Ethibloc in the treatment of cystic and venous angiomas in children. 19 cases. AB - The authors report the use of Ethibloc in the treatment of cystic lymphangiomas and venous angiomas in 19 children. This embolizing product is injected by puncture in situ. Ten cystic lymphangiomas were treated, including 7 of the cervico-facial region. Of these ten, 8 were embolized initially using Ethibloc, and 2 after surgery. The diagnosis was always confirmed by echography and in some cases also by scanner. Six were completely cured and 2 had partial but satisfactory results requiring further injections. The final 2 cases when Ethibloc was administered after surgery, gave very disappointing results as the residual lesion was microcystic and thus difficult to access for the Ethibloc injection. The 9 venous angiomas involved various regions, including 5 facial lesions. These angiomas required a more extensive blood-clotting and radiologic assessment: standard radiography to detect the clot, Doppler echography and M.R.I. precisely clarifying the exact extension in depth. For 6 patients the cure was complete, for 2 others the results were good. Finally, in 1 case Ethibloc embolization was carried out prior to surgery, allowing definitive cure. In all, this technique resulted in a complete cure in 2/3 of the cases and its simplicity makes it a seemingly interesting alternative to surgery. PMID- 8353119 TI - The Rapunzel syndrome: a case report and review of the literature. AB - The Rapunzel syndrome, found characteristically in girls with varying gastrointestinal symptoms, is a rare form of gastric trichobezoar extending throughout the bowel. The previously reported cases have different clinical and pathological features affecting the mortality. We describe a new case preoperatively diagnosed with none of the complications previously reported. PMID- 8353120 TI - Splenoptosis (wandering spleen). AB - Splenoptosis which is a congenital fusion anomaly of dorsal mesogastrium in children is a very rare entity. In the literature cases are usually diagnosed at operation and it is noted that in former years splenectomy had a special place among various methods of treatment. In this report, a 7-year-old case of splenoptosis diagnosed on ultrasonography and isotope scintigraphic methods preoperatively and treated by splenopexy is presented. In cases with splenoptosis the clinical and radiologic diagnostic criteria are given and the importance of splenopexy in treatment is emphasized. PMID- 8353121 TI - The abdominoscrotal hydrocele. AB - While hydrocele is among the commonest inguinal anomalies in children, less than 20 cases have been reported of its extreme form, the abdominoscrotal hydrocele (ASH). This anomaly consists of a large inguinoscrotal hydrocele which communicates in an hour-glass fashion with a large "intra-abdominal" component. The latter lies deep to the narrow internal inguinal ring, but superficial to the peritoneal cavity proper, which is displaced superiorly and medially. The abdominal component of the ASH thus lies latero- and retroperitoneally, sometimes reaching the lower pole of the kidney. We report five ASH in four children under one year old. All four underwent complete resection of the ASH. If the abdominal portion of the hydrocele can not be delivered through a standard approach, we advocate a properitoneal approach as described for recurrent adult hernias. The external oblique, internal oblique and transversalis muscles are divided horizontally above the level of the internal inguinal ring. The peritoneal cavity is retracted superiorly, separating it from the ASH. By decompressing the scrotal component of the ASH, its abdominal part can be emptied through the narrow communication at the internal ring. In this fashion, the processus vaginalis can be identified and ligated deep to internal ring, and the floor of the inguinal canal is left intact. The pathophysiology of ASH is not clear. A one-way valve effect of the patent processus vaginalis may be one cause of the massive accumulation of peritoneal fluid in the ASH. Complete resection is curative, and the properitoneal approach should be considered. PMID- 8353122 TI - Infantile myofibromatosis: an unusual presentation and a review of the literature. AB - An infant with an unusual presentation of Infantile Myofibromatosis (IM) is presented. Massive involvement of the pelvic region complicated the delivery and precluded meaningful therapy. The literature is reviewed. PMID- 8353123 TI - Tailgut remnant--or teratoma? AB - The tailgut is the distalmost portion of the embryonic gut, located caudal to the cloacal membrane. Up to the sixth week of development, it is in close proximity to the distal end of the notochord and the neural tube. It completely regresses by the seventh week, but some caudal duplication-like cysts have been attributed to its remnants. We report a full-term male born with a large heterogeneous sacral mass. Severe bony abnormalities of the coccyx, sacrum and lower lumbar vertebrae were present, but the infant was neurologically intact. At surgery, the upper cystic structures within the mass were found to communicate with the dura, while the solid component, whose surface resembled intestinal mucosal folds, was closely related to the perirectal tissues. The mass was completely resected and the dura oversewn. Since this complex mass contained all three cell lines in an aberrant location, it satisfies the definition of a sacrococcygeal teratoma. However, its unique architecture suggests a malformative, rather than tumoral origin. The macroscopic appearance of this lesion reflects the embryonic relationship between the tailgut, the neural tube and the notochord. PMID- 8353124 TI - Cone epiphysis of the knee and scurvy. AB - A rare case of metaphyseal cupping of the distal femur resulting from infantile scury in a child is reported. The radiological and surgical aspects of this case are of particular interest. MRI demonstrated central epiphysiodesis of the right knee, surgery achieved rupture of the epiphyseal plate and resulted in femoral lengthening. The child's limp disappeared as a result. PMID- 8353125 TI - Does fibrin glue cause foreign body reactions? PMID- 8353126 TI - Improved purification and biochemical characterization of phospholipase D from cabbage. AB - Phospholipase D (phosphatidylcholine phosphatidohydrolase, EC 3.1.4.4) was purified from cabbage leaves. The two step purification procedure involved hydrophobic chromatography on Octyl-Sepharose followed by a Mono-Q/FPLC-column with a total yield of 23% and a purification factor of 1000. A zymographic assay was used to detection of PL D activities at various stages of purification under non denaturing PAGE. The molecular mass was determined to be 90 kDa using the SDS/PAGE method, and 90,200 Da as calculated from the amino acid analysis. The isoelectric point of the enzyme is acidic (pI = 4.7). The amino-acid composition and 29 residues of the NH2-terminal amino-acid sequence were determined. PMID- 8353127 TI - Two open reading frames adjacent to the Escherichia coli K-12 transketolase (tkt) gene show high similarity to the mannitol phosphotransferase system enzymes from Escherichia coli and various gram-positive bacteria. AB - I have subcloned and sequenced the genes cmtB and cmtA of Escherichia coli K-12 which lie adjacent to the tkt gene on the chromosome. The genes cmtB and cmtA could encode a cytoplasmic protein (EIIA) and an integral-membrane protein (EIIBC), respectively, of the bacterial phospho enol pyruvate-dependent carbohydrate phosphotransferase system. High similarity to the Enzymes IIMtl of Escherichia coli K-12 (gene mtlA) and of Staphylococcus carnosus was detected, but the two genes did not complement mannitol-negative E. coli mutants without the use of a heterologous promoter. PMID- 8353128 TI - Kinetic studies on the reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney. AB - The kinetic mechanism for the reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney was investigated. The initial velocity and product inhibition studies indicated that the enzymatic reaction follows an ordered Bi Bi mechanism, in which NADPH binds to the enzyme first and NADP leaves last. This kinetic mechanism was confirmed on the basis of the dead-end inhibition by Cibacron Blue and the binding of NADPH and NADP to the free enzyme. However, whether or not coenzyme-induced isomerization is involved in the enzymatic reaction remains to be clarified. In kinetic studies of inhibition of the enzyme by therapeutically active drugs, indomethacin and befunolol were found to be noncompetitive and competitive inhibitors, respectively, with respect to acetohexamide. PMID- 8353129 TI - Purification and partial characterization of a mitogenic lectin from the latex of Euphorbia marginata. AB - A lectin was purified from the latex of Euphorbia marginata by affinity chromatography on acid-treated Sepharose 6B and elution with lactose. The lectin is a glycoprotein composed of two identical subunits with M(r) 30,000, approx. The haemagglutinating activity of the lectin is not specific for any human blood group, and is inhibited by galactose and galactose-containing sugars and by gentiobiose. The lectin is strongly mitogenic for human T-lymphocytes and induces the release of interleukin-1 beta and tumor necrosis factor-alpha from cultured mononuclear cells. PMID- 8353130 TI - Higher-order dielectrophoretic effects: levitation at a field null. AB - Experiments with certain new micro-electrode structures used to achieve passive dielectrophoretic levitation of small particles and biological cells reveal a pronounced size-dependent effect not anticipated by the conventional dipole-based model. The conventional theory fails to predict this size effect because it neglects higher-order moments such as the quadrupole, hexapole, and octupole. These higher-order moments are in fact responsible for the levitation force achieved by azimuthally periodic electrode structures because, in such geometries, the electric field is zero along the axis so that the induced dipole moment must be zero. For example, the planar quadrupole levitates particles passively along the central axis through the interaction of its field with the induced quadrupolar moment of the particle. The size effect reported with this structure is readily explained in terms of this quadrupolar component of the ponderomotive force exerted on the particle. PMID- 8353131 TI - The absence of glyoxylate cycle enzymes in rodent and embryonic chick liver. AB - There have been several reports over the past decade of the presence of the glyoxylate cycle enzymes, isocitrate lyase and malate synthase, in animal tissues. Reaction products in these assays have been measured principally by chromatographic separation of isotopes or by colorimetric procedures. In this report more sensitive and accurate HPLC and HPCE analyses were used to detect enzymatic activity. Reversed phase HPLC revealed the absence of detectable isocitrate lyase activity in guinea pig, rat and chick embryonic liver. The formation of several other alpha-keto acids was detected and this may account for the previously reported activities. Using HPCE to monitor malate formation malate synthase activity was not detected in these tissues. These results indicate that when assaying enzyme activities in crude tissue homogenates specific methods for the identification of end products are required. PMID- 8353132 TI - Mithramycin: a very strong metal chelating agent. AB - The interaction of mithramycin (MTR) with Ca2+, Cd2+, Tb3+, Gd3+, Li+, Na+ and K+ ions has been studied by circular dichroism and absorption spectroscopy. Mithramycin binds strongly to Ca2+, Cd2+, Tb3+ and Gd3+ forming a 1:4 Ca2+: MTR entities with a left-handed screw conformation. The concentration of Ca2+ present in water currently used being about 10 microM, this leads to the conclusion that, in most of the experiments reported in the literature, about 40 microM mithramycin were actually bound to Ca2+. Mithramycin also binds to Na+, forming entities with left-handed screw conformation, but not to K+ and Li+. None of these cations were able to promote the mithramycin-DNA interaction. PMID- 8353133 TI - Hemoglobin multiple emulsion as an oxygen delivery system. AB - Multiple emulsion technology provides a mechanism for the encapsulation and in vivo delivery of drugs, proteins, and other materials which would otherwise be degraded, cleared rapidly, or toxic to the host. These feasibility studies were performed to evaluate a prototype Hb multiple emulsion as a stable oxygen delivery system. A concentrated solution of hemoglobin (Hb) was encapsulated in the form of a Hb-in-oil-in-water (Hb/O/W) multiple emulsion. Studies using mineral oil demonstrated that Hb multiple emulsions have several important characteristics that are compatible with utility as a blood substitute. These include: satisfactory rheological properties and good hydrodynamic stability compared to whole blood, high encapsulation concentration of Hb and high encapsulation efficiency with little met-hemoglobin generation, and satisfactory oxygen affinity and cooperativity compared to whole blood. Isovolemic exchange transfusions of Hb/O/W multiple emulsion can support life in rats whose hematocrit has been reduced to levels (5% or lower) that are incompatible with survival, and induces no acute toxicity. These results are consistent with the utility of Hb/O/W as an oxygen-carrying red blood cell substitute or organ perfusion media. PMID- 8353134 TI - A pulse radiolysis study of the reactions of 3-hydroxykynurenine and kynurenine with oxidizing and reducing radicals. AB - Pulse radiolysis has been used to study the reactions of 3-hydroxykynurenine and kynurenine with solvated electrons, superoxide radicals, hydroxyl radicals and azide radicals. Both 3-hydroxykynurenine and kynurenine react with solvated electrons with diffusion controlled rate constants (k = 2.5 x 10(10) M-1 s-1 and 2.3 x 10(10) M-1s-1, respectively). Neither compound was observed to react with superoxide radicals under our experimental conditions, an upper limit of 1.2 x 10(5) M-1s-1 for the rate constant of this reaction was estimated for both compounds. However, we do observe that a stable product of autooxidation of 3 hydroxy-kynurenine reacts with superoxide radicals and we calculate a lower limit for the rate of this reaction of 5.8 x 10(6) M-1s-1. Reactions of 3 hydroxykynurenine and kynurenine with hydroxyl radicals proceed with diffusion controlled rate constants (1.2 x 10(10) M-1 s-1 and 1.3 x 10(10) M-1 s-1, respectively). The measured values for the rate constants for reaction of 3 hydroxykynurenine and kynurenine with azide radicals are 2.1 x 10(10) M-1s-1 and 4.8 x 10(9) M-1 s-1, respectively. The differences in these rate constants are attributed to differences in the measured oxidation potentials for 3 hydroxykynurenine (+1.0 V vs. NHE) and kynurenine (+1.15 V vs. NHE). PMID- 8353135 TI - Effect of insulin and glucose load on bile lactate secretion by the isolated rat liver. Role of hepatic parenchyma heterogeneity. AB - Parenchymal heterogeneity in lactate disposal by perivenous and periportal hepatocytes is believed to be an important factor affecting the overall lactate metabolism by the liver. The aim of this work was to investigate the possibility of the existence of a different role of both acinar zones 1 and 3 in lactate secretion into bile. The effect of insulin and glucose load was also studied using isolated in situ rat liver preparations. Perfusions with erythrocyte-free Krebs-Henseleit solutions were carried out in intact livers and after restricted damage of zone 1 or zone 3 by digitonin administration as a bolus through the portal or the hepatic vein, respectively. In intact livers lactate concentrations in bile were similar to those found in the perfusate. In both compartments lactate concentrations were observed to increase over 90 min of perfusion. During this time, bile lactate output increased from 5 to 8 nmol/min per g liver with no significant effect on bile flow. Replacement of perfusate by a fresh lactate-free one at 60 min failed to induce any reduction in lactate concentration in bile samples collected during the following 30 min which suggests the absence of easy equilibration of biliary lactate with the sinusoidal compartment. Insulin administration (bolus: 100 mU/100 g body weight, plus portal infusion: 5 mU/min per 100 g body weight) was found to markedly enhance bile lactate concentrations (+110%) and output (+139%). On the contrary, glucose load was found to have no effect on lactate output into bile. No significant difference in the increase in bile lactate output was observed during 90 min perfusion with either 0, 5, 10, 15, 25 or 35 mM initial glucose concentrations. After restricted damage of acinar zone 1 or 3, insulin-induced bile lactate secretion was significantly reduced. This effect was not different regardless the damaged acinar zone. In summary these results suggest that insulin plays an important role in the control of the output of lactate into bile and that the existence of acinar heterogeneity in this function seems unlikely. Moreover the quantitative contribution of bile lactate to overall lactate handling by the liver and to bile formation seems very low. PMID- 8353136 TI - Regulation of hyaluronate production by interleukin 1 in cultured human chorionic cells. AB - Human chorionic cells in culture synthesized and secreted a large amount of hyaluronate as well as tissue collagenase. When these cells were treated with human recombinant interleukin 1 alpha (hrIL-1), the biosynthesis and secretion of hyaluronate were predominantly accelerated, but those of sulfated glycosaminoglycans were not modulated. This promotive effect of hrIL-1 was not due to the increase in endogenous prostaglandins including prostaglandin E2 since cyclooxygenase inhibitors, indomethacin and diclofenac did not modulate the IL-1 mediated production of hyaluronate. On the other hand, the cotreatment of chorionic cells with hrIL-1 and cycloheximide suppressed the IL-1-mediated hyaluronate production, suggesting that protein, de novo, synthesis required for the enhancement of hyaluronate synthesis. Upon treatment with hrIL-1, the membrane bound-hyaluronate synthase activity was increased up to 5-fold in a time dependent manner. On the other hand, when chorionic cells were treated with hrIL 1 and/or protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methyl pyperadine hydrochloride (H7), the IL-1-mediated production of hyaluronate was effectively suppressed. Similarly, H7 effectively suppressed the protein kinase activator, 12-O-tetradecanoyl-phorbol-13-acetate-enhanced production of glycosaminoglycans with a similar extent. These results indicate that IL-1 induced acceleration of hyaluronate production was reflected on the increase in hyaluronate synthase activity, and that protein kinase C participates positively in the IL-1-signal transduction for the increased synthesis of hyaluronate in human chorionic cells. PMID- 8353137 TI - The induction of intracellular calcium activity in cultured human myometrial smooth muscle cells. AB - Cells maintained in serum free medium for 24 hours were found to have a higher incidence of both spontaneous increases in intracellular calcium ([Ca2+]i) (Ca2+ spikes) and small random changes in [Ca2+]i (Ca2+ 'noise'). The spontaneous transient increases in [Ca2+]i and the Ca2+ 'noise' disappear in solutions containing nominally zero Ca2+. PMID- 8353138 TI - Estrogen regulation of proto-oncogenes coding for nuclear proteins. AB - Estrogen hormones are known to exert a complex influence on development and function of the female reproductive organs of vertebrates by regulating cell growth and differentiation, as well as to be implicated in oncogenesis and maintenance of tumor growth. Estrogen acts on cells via interaction with an intracellular receptor, which, like all receptors for steroid hormones, is a trans-acting transcription enhancer factor activated by the cognate ligand and capable of binding to specific, cis-acting enhancer elements usually located within the 5'-flanking regions of target genes. Additionally, estrogen regulates gene expression by influencing mRNA stability or via interaction of the estrogen receptor with transcription regulatory factors. This article reviews data indicating that estrogen directly activates (primary activation) expression of proto-oncogenes codifying for nuclear proteins that, in turn, are responsible for indirect (secondary) activation of other genes. This cascade mechanism of gene activation is likely to progress for several more steps and allows us to envisage how estrogen can direct a complex task such as cell reproduction. Among proto oncogenes codifying for nuclear proteins, we focus on fos, jun, myc, and related genes. The mechanisms of regulation of these genes by estrogen, including regulation of transcription, messenger RNA stabilization, and protein-protein interaction, are reviewed. PMID- 8353139 TI - Role of GTPases and GTPase regulatory proteins in oncogenesis. AB - The GTPases comprise a superfamily of GTP-binding proteins with intrinsic GTPase activity. Some members of this family representing either heterotrimeric or small G-proteins are involved in the transmission of mitogenic signals. Mutations that lead to constitutively activated G-proteins have been shown to contribute to malignant transformation. These genes represent, therefore, putative oncogenes. Examples are the gsp and gip2 oncogenes, encoding GTPase deficient alpha-subnits of Gs or Gi-2 proteins. Representatives from the family of small G-proteins are the products of the Harvey-, Kirsten- or N-ras oncogenes. These oncogenes, which are frequently expressed in human malignancies, code for proteins (p21ras) that are locked in the activated GTP-bound state because their GTPase is refractory to the ras-specific GTPase activating protein (GAP). In other cases p21ras-GTP levels have been found to be elevated as a result of an increase in GDP/GTP exchange rate. In neurofibromatosis v. Recklinghausen, a mutated gene (NF1) is detectable. The protein encoded by NF1 contains a GAP homology region, binds p21ras-GTP, and stimulates the hydrolysis of p21ras-bound GTP. Both ras-GAP (p120 GAP) and NF1-GAP are inhibited by acidic lipids. Elevated levels of these lipids may exert growth-stimulatory or perhaps tumor-promoting activity by increasing p21ras GTP. The function of transforming p21ras is under control of tumor suppressor genes. Putative suppressor genes isolated from revertants from ras transformed cells include rsp-1 and the ras recision gene (rrg). Experimentally, an overexpression of Rap 1A/Krev-1 is able to antagonize transformation by p21ras. This mechanism also may be relevant under normal conditions. p53 also is capable of inhibiting transforming p21ras. It is postulated that p105-RB exerts a similar anti-ras effect. The mechanism by which retinoic acid suppresses transformation by ras is discussed. Current strategies for a pharmacological interference of p21ras function are described. PMID- 8353140 TI - A critical approach to the malignant transformation of human breast epithelial cells with chemical carcinogens. AB - This work was undertaken with the purpose of clarifying the factors that modulate the transformation of human breast epithelial cells. For accomplishing this goal, it was necessary to establish the adequate culture conditions for maintaining primary cultures of breast tissue for their treatment with genotoxic agents. It also was determined whether primary cultures generated from these tissues maintained the basic biological properties of the host. In this work we have been able to show that the in vivo developmental stage of the gland is important in the expression of an early transformation phenotype after treatment with chemical carcinogens in vitro; furthermore, that the culture conditions, mainly the calcium concentration in the medium, are important in the selection of that specific phenotype. Four carcinogens, 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (BP), methyl-N-nitro-nitrosoguanidine (MNNG), and N-methyl-N nitrosourea (NMU) were used for treating primary human breast epithelial cell (HBEC) cultures. Ten out of 20 samples tested expressed survival efficiency in agar methocel. The immortalized human breast epithelial cell line MCF-10 was treated with the same chemical carcinogens, which induced point mutations in codons 12 and 61 and the expression of malignant phenotypes in treated cells. MCF 10 cells transfected with the mutated c-Ha-ras gene exhibited the same malignant phenotypes shown by carcinogen-treated cells, mainly tumorigenesis in SCID mice. It was concluded that both chemical carcinogens and mutated ras gene induce malignant transformation of immortalized HBEC, which suggests that the critical point in the transformation pathway is the immortalization of the cell. PMID- 8353141 TI - Detection of cancer by tumor markers in the blood: a view to the future. AB - Markers for cancers in the blood include secreted glycoproteins of solid tissue tumors as well as cell surface markers, and chromosomal rearrangements or mutated genes in circulating blood cells. The most successful markers for the diagnosis of solid tissue cancers have been alphafetoprotein and prostate specific antigen. Other markers, such as CEA and a number of carbohydrate epitopes, e.g., CA 15.3, CA 19.9, CA 50, CA 242, and mucin epitopes, such as MCA, CA 125, and DU-PAN-2 are now being used to determine prognosis and to monitor the response to therapy of a variety of cancers. Cytologic markers in the blood include clusters of differentiation (CD) epitopes on blood cells and chromosomal changes, primarily translocations found in many human lymphomas. In the future more specific mutations in specific oncogenes or alterations in expression of oncogenes or suppressor genes, such as p53, may provide clinically useful markers. PMID- 8353142 TI - The c-myc oncogene in tumor progression. AB - Tumor progression is a complex process involving many alternative molecular pathways that are often tissue and/or species specific. The c-myc oncogene has been implicated in malignant progression in a variety of human tumors. In many instances, amplification and/or elevated expression of the c-myc gene have been associated with poor prognosis or decreased survival; in other cases, correlations have been demonstrated between c-myc activation and specific parameters of advanced neoplastic stage such as hormone independence, transplantability, invasiveness, etc. The tumor types exhibiting c-myc as a "progressor" gene include breast, colon, small cell lung carcinoma, as well as ovarian cancer, lymphomas, and squamous cell carcinomas. The c-myc oncogene has been implicated in a number of experimental animal tumor models, especially rat liver. Several studies have found that c-myc often functions in rodent tumor progression. For example, rat skin carcinomas induced by ionizing radiation show c-myc amplification to be related directly to tumor size and age. PMID- 8353143 TI - Phosphotyrosyl protein phosphatases: potential regulators of cell proliferation and differentiation. AB - Tyrosyl phosphorylated proteins have been associated with the regulation of cellular activities, including proliferation, differentiation, and transformation. The overall cellular levels of tyrosyl phosphorylated proteins are regulated by the balance of the activities of both tyrosyl protein kinases and phosphotyrosyl protein phosphatases. Until recently, it was generally assumed that the kinase reaction was the key regulatory process for determining the level of tyrosyl phosphorylated proteins and that the dephosphorylation reaction was an unregulated event. However, recent evidence strongly suggest a regulatory role for phosphotyrosyl protein phosphatases for determination of the overall level of tyrosyl phosphorylated proteins. This review focuses on the discussion of the properties, the regulation, and the primary structure of phosphotyrosyl protein phosphatases. Evidence that supports an important role for phosphotyrosyl protein phosphatases on cell proliferation and differentiation also is presented. PMID- 8353144 TI - Targeting lung cancer genes: a novel approach to cancer prevention and therapy. PMID- 8353145 TI - The thoracic surgeon's role in smoking cessation and prevention. PMID- 8353146 TI - Chemoprevention of lung cancer. PMID- 8353147 TI - Lasers for the early detection of lung cancer. PMID- 8353148 TI - Monoclonal antibodies for early cytologic detection of lung cancer. PMID- 8353149 TI - Significance of lymph node metastases in lung cancer. PMID- 8353150 TI - The role of thoracoscopy in the management of intrathoracic neoplastic processes. PMID- 8353151 TI - Sleeve resections for lung cancer. PMID- 8353152 TI - Surgery for stage N2 lung cancer. PMID- 8353153 TI - Chemotherapy and radiation therapy for lung cancer. PMID- 8353154 TI - Placental transfer of free fatty acids: importance of fetal albumin concentration and acid-base status. AB - Free fatty acids (FFA) are the main class of naturally occurring lipids transferred across the placenta, irrespective of species. In order to study the importance of fetal plasma albumin concentration and pH on placental transfer of FFA, in situ perfusion of the rabbit placenta in late gestation was used as an experimental model. Increasing albumin concentration on the fetal side of the placenta from 1 to 6% significantly increased transfer of FFA across the placenta. However, alteration of the umbilical perfusate pH in the range 7.0-7.5 had no significant effect. PMID- 8353155 TI - Soluble interleukin-2 receptor and interleukin-2 in human amniotic fluid of normal and abnormal pregnancies. AB - In the present study, 63 specimens of human amniotic fluid were tested for the presence of free soluble interleukin-2 receptor (IL-2R). Thirty-two of these were also tested for the presence of IL-2. Significant reduction in free soluble IL-2R (IU/ml) or free IL-2R (IU/mg albumin) levels were found in the amniotic fluid obtained from pregnant women with Down's syndrome fetuses as compared with normal pregnancies. In addition normal amniotic fluid was found to contain low levels of IL-2, while no IL-2 was found in amniotic fluid from pregnant women with Down's syndrome fetuses when tested by two different tests. PMID- 8353156 TI - Cobalt-mesoporphyrin inhibits heme oxygenase activity but it does not induce lipid peroxidation in rat brain membranes during photoirradiation. AB - We examined the effects of cobalt-mesoporphyrin (CoMP) in vitro. The porphyrin inhibited the activity of rat splenic heme oxygenase but scarcely stimulated peroxidation of lipids in a membrane fraction from rat brain during photoirradiation. The apparent inhibition constant for CoMP was 344 nM. It is suggested that CoMP may be a promising candidate for a chemopreventive of neonatal hyperbilirubinemia that is not associated with phototoxicity. PMID- 8353157 TI - Acute effects of cocaine on ornithine decarboxylase activity in fetal and neonatal rat heart: evidence for cardiotoxicity. AB - Fetal exposure to cocaine is associated with increased perinatal cardiac risk. In the current study, we examined the effects of acute cocaine administration on ornithine decarboxylase (ODC) activity in fetal and neonatal rat heart. ODC is a key regulatory enzyme in the control of cell differentiation and growth, and rapid changes in ODC are associated with the response to cell injury. Administration of 30 mg/kg s.c. of cocaine to pregnant rats on the 20th day of gestation caused acute elevation of fetal cardiac ODC that persisted throughout the ensuing 24 h. In contrast, the same dose given directly to neonatal rats the day after birth evoked only a short-term (1-h) stimulation of ODC that was reversed by 4 h after treatment. By 4 days of age and subsequently, cocaine was unable to elicit acute stimulation of heart ODC and only evoked inhibition of enzyme activity. Elevated progesterone levels during pregnancy have been shown to sensitize the maternal myocardium to cocaine-induced catecholaminergic effects; the greater sensitivity of fetal heart ODC to cocaine, as compared to neonatal heart, supports the hypothesis that similar enhancement of fetal cardiac irritability can contribute to cocaine-induced cell damage. PMID- 8353158 TI - Lipoxygenase activity in rat embryos and its potential for xenobiotic oxidation. AB - This paper reports dioxygenase activity in rat embryos and demonstrates for the first time the ability of rat embryo lipoxygenase (LO) to oxidize xenobiotics in vitro. Significant dioxygenase activity towards linoleic acid was found in cytosol isolated from rat embryos in different developmental stages on day 9 and 10 of gestation. All four xenobiotics tested were oxidized at significant rate by the LO in the presence of linoleic acid. Both dioxygenase activity and benzidine oxidation were inhibited by the known inhibitors of LO, i.e. nordihydroguaiaretic acid and eicosatriynoic acid. These findings suggest that LO may be an important pathway for xenobiotic metabolism in the rat embryo. PMID- 8353159 TI - Effects of epidermal growth factor on ornithine decarboxylase activity and DNA synthesis in rats during the perinatal period. AB - The effects of epidermal growth factor (EGF) on ornithine decarboxylase (ODC) activity and DNA synthesis were studied during the perinatal period in rats. EGF administration to neonatal rats increased ODC activity and DNA synthesis in neonatal rat liver, but not in brain. EGF administration to maternal rats increased ODC activity in maternal rat liver, but not in rat placenta and fetal rat liver. These data suggest that EGF has mitogenic effects on neonatal and maternal rat liver and play some important roles in fetal and neonatal growth. PMID- 8353160 TI - Stimulatory effects of insulin on DNA synthesis in suckling mouse colon. AB - The influence of insulin on the postnatal development of DNA synthesis and epithelial and muscular cell proliferation has been studied in suckling mice. Daily administration of insulin (12.5 mU/g body weight) during 3 days to 8-day old mice induced a significant increase of the incorporation of [3H]-thymidine into DNA in the small intestine and the proximal and distal halves of the colon. The esophagus and the glandular portion of the stomach did not respond. A detailed analysis of the proximal and distal colon between 4 and 30 days revealed a decrease of [3H]-thymidine incorporation into total DNA during this period. However, the establishment of the labeling indices in specific compartments such as the epithelium and the muscularis externa revealed that the epithelial cellular proliferation increased around weaning period in both segments while a drastic reduction of cellular proliferation occurred in the muscle layer. A premature rise of the circulating insulin level induced a significant increase of the epithelial labeling indices in both colonic segments but remained without effects on the muscular layer. These results suggest an important role of insulin in the modulation of the ontogenic changes in epithelial cell proliferation of the mouse colon. PMID- 8353161 TI - Falling intracranial pressure: an important element in the genesis of intracranial hemorrhage in the beagle puppy. AB - To study the role of extravascular intracranial pressure (ICP) in the genesis of intracranial hemorrhage in the beagle puppy, we measured ICP in animals on the day of birth, untreated 3-day-old controls, and 3-day-old animals treated from birth with prolactin. Baseline ICP varied substantially in all 3 groups. Only 8% of this variability was attributable to variability in mean arterial pressure and central venous pressure. ICP was lower in the 3-day-old controls, animals at high risk for intracranial hemorrhage after a hypovolemic/hypotensive insult followed by rapid volume expansion, than in the other groups which are at lower risk. Administration of a hyperosmolar insult, intraperitoneal glycerol, to animals whose ICP was relatively high promptly lowered ICP. After this treatment, the risk of intracranial hemorrhage was markedly increased in these previously low risk groups. We conclude that the normal neonatal decrease in brain water content and the consequent fall in ICP substantially increase the risk of intracranial hemorrhage in the beagle puppy, a model which appears similar in pathophysiology to hemorrhage in the preterm human infant. PMID- 8353162 TI - Breast feeding and formula feeding affect differently plasma thyroid hormone concentrations in infant baboons. AB - We tested the hypothesis that plasma thyroid hormone levels in infant baboons are differentially affected by breast-feeding and nursery rearing. Infant baboons were breast-fed (n = 17), or fed formulas with a high polyunsaturated to saturated fat ratio (P/S) (n = 13), or a low P/S formula (n = 14). Plasma total triiodothyronine (T3) and free T3 (fT3) concentrations increased from 4 to 14 weeks of age in infants fed either formula, but decreased in breast-fed infants. At 9 and 14 weeks of age, infants fed the formulas averaged 31% higher T3 and 53% higher fT3 concentrations compared with breast-fed infants. Although T3 concentrations of the high P/S formula group compared with the low P/S formula group were not different at any single age, from 4 to 14 weeks the T3 averaged 19% higher in the high P/S formula group. Plasma total thyroxine (T4) or free T4 (fT4) concentrations were not significantly different among the diet groups during the preweaning period. In summary, formula-fed infants maintained higher plasma T3 and fT3 levels compared with breast-fed infants in the late preweaning period. PMID- 8353163 TI - Reduced levels of alpha-1-antitrypsin in children exposed to high levels of air pollution. AB - Health risks associated with environmental pollution, particularly in Eastern Europe, are a cause for concern. In order to gain some insight into the effects of exposure to high levels of air pollution particularly by heavy metals, we measured the concentration of nine plasma proteins in plasma samples from newborn babies and 5- to 6-year old children living in heavily polluted areas of Poland, as well as from some newborns and adults from unpolluted areas of Poland and control samples within the local Southampton population. The concentrations of all proteins measured were in or close to their expected range, with the exception of alpha 1-antitrypsin (alpha 1AT). The concentration of this protein was lower in both groups of Polish children from the polluted areas, particularly in the 5- to 6-year old group. These children were shown to be phenotypically normal. Since adult levels of alpha 1AT are usually reached within 2 weeks postpartum, these findings raise the possibility that continued exposure to high levels of pollution may lead to reduced levels of alpha 1AT in plasma; this may compound the impairment of lung function in children living in highly polluted areas. PMID- 8353164 TI - Depression in stroke rehabilitation. AB - Despite recent advances in understanding the pathophysiology of poststroke depression, major questions remain. They include the relative importance of lesion location and size and the confounding effects of time since stroke, age, prior history of depression, and cerebral atrophy. To evaluate these issues, we systematically assessed depressive features, functional status, and brain structure with computer tomography scans in 91 men undergoing stroke rehabilitation. Forty percent met DSM-III criteria for major depressive disorder. Mood disturbance was more severe for patients with right than with left hemisphere lesions, correlated with functional disability and lesion size, and was associated with previous history of depression. Age, time since stroke, and atrophy did not correlate with mood. Depression is common in delayed stroke recovery, regardless of lesion location. Because there are no demographic or anatomic features that predict the absence of depression, depression screening should be part of the assessment of all patients undergoing stroke rehabilitation. PMID- 8353165 TI - Amphetamine-produced attenuation of latent inhibition is modulated by stimulus preexposure duration: implications for schizophrenia. AB - The relationship between amphetamine-produced dopamine overreactivity and attention to irrelevant stimuli is reflected in an attenuated latent inhibition (LI) effect. This occurs in both animal and human subjects. The present study examines the manner in which this effect in rats is modulated by the duration of stimulus preexposure. A factorial design was used with three levels of stimulus preexposure duration and either amphetamine or saline administration. In addition, there were corresponding groups that did not receive stimulus preexposure. It was found that although amphetamine did indeed abolish LI at short exposure intervals (30 sec), the LI effect was normal for long stimulus preexposure durations (150 sec). The data were discussed in terms of the affects of amphetamine on the processing of irrelevant stimuli and the relationship of such a dysfunctional attentional process to schizophrenia. PMID- 8353166 TI - Indole-pyruvic acid, a tryptophan ketoanalogue, antagonizes the endocrine but not the behavioral effects of repeated stress in a model of depression. AB - Increased glucocorticoid secretion is frequent in mood disorders and is normalized by long-term antidepressant therapy. Many antidepressants act by increasing central serotonin transmission. We investigated the effects of a serotonin precursor, indole-pyruvic acid (IPA), in an animal model of depression based on repeated exposure to unpredictable stress. Rats were divided in groups, and IPA (20 mg/kg), the tricyclic antidepressant imipramine (IMI) (5 mg/kg), or vehicle was administered daily during 3 weeks of repeated exposure to various stressors according to the procedure described by Katz et al [Katz RJ, Roth KA, Carroll BJ (1981): Neurosci Biobehav Rev 5:247-251]. After treatment, rats were evaluated for stress-induced exploratory behavior and killed 24 hr later. Serum corticosterone levels and glucocorticoid receptor (GR) immunoreactivity (IR) in the nuclei of neurons located in the hippocampal subregion CA1 were also measured. Rats exposed to repeated stress showed a lower exploratory behavior score (p < 0.01), higher basal corticosterone levels (p < 0.01), and stronger GR IR in the hippocampus (p < 0.05) than control rats. All of these effects were antagonized by IMI treatment. IPA administration did not affect the behavioral response induced by repeated stress (p < 0.01) but normalized serum corticosterone levels. In addition, IPA treatment produced a decrease in GR IR (p < 0.05 versus control group) that was not modified by exposure to repeated stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353167 TI - N200 component of event-related potentials in depression. AB - Event-related potentials (ERPs) recorded during a two-tone discrimination (oddball) task were examined in 36 drug-free depressed patients and 36 control subjects. At remission, the ERPs of 12 of the depressed patients were reexamined. In the depressed patients, although a group difference was not detected in the peak latency and amplitude of N200 to rare stimuli, the mean amplitude for the N200 latency range in the difference waves was smaller than in the control subjects. Mismatch negativity (N2a), which was elicited by rare stimuli, was reduced in amplitude; but N2b may have been evoked to frequent stimuli more in the patients than in the control subjects. Depressed subjects may have a deviance in the fully automatic cerebral mismatch process that is assumed to be related to mismatch negativity and provoke the controlled mismatch detection process (presumed to be associated with N2b) even to nontarget frequent stimuli. These findings were observed during remission; however, there was a tendency for the N2b amplitude to decrease and recover toward the level of the control subjects. PMID- 8353168 TI - 3H-spiroperidol binding to peripheral mononuclear cells in schizophrenic and healthy subjects. AB - 3H-spiroperidol binding to peripheral blood mononuclear cells was measured in 28 patients, who fulfilled DSM-III-R-criteria for schizophrenia and 17 healthy subjects. There were no significant differences in characteristic binding parameters (Kd, Bmax) between schizophrenic and healthy subjects. Moreover, there was no relation of binding parameters to any of the subtypes of schizophrenia or to the course of illness according to DSM-III-R-criteria. However, some patients exhibited higher Bmax values without having a unique clinical symptomatology according to known diagnostic criteria. Neuroleptic treatment had no consistent effect on binding parameters intraindividually. Kd and Bmax values were not related to age or gender. In conclusion, despite our previously reported improved methodology, we were not able to corroborate the clinical importance of this "peripheral marker" as a tool for diagnosing schizophrenia or for predicting the response to neuroleptic treatment in our sample of schizophrenic patients. PMID- 8353169 TI - Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. AB - The cerebrospinal fluid (CSF) of 47 children and adolescents with autism was analyzed for the contents of two astroglial proteins, the glial fibrillary acidic protein (GFA) and S 100. The results were contrasted with those obtained in similarly aged cases with other neuropsychiatric disorders (n = 25) and in normal children (n = 10). S-100 did not discriminate the groups from each other. However, GFA in autism and autistic-like conditions was at a level almost three times that in the normal group. The results could implicate gliosis and unspecific brain damage in autism. An alternative model would be increased synapse turnover regardless of underlying cause. PMID- 8353170 TI - A pilot study of biological predictors of treatment outcome in obsessive compulsive disorder. PMID- 8353171 TI - Auditory-evoked responses in chronic alcohol and drug abusers. PMID- 8353172 TI - THA does not affect sleep or EEG spectral power in Alzheimer's disease. PMID- 8353173 TI - The noncompliance factor in the dexamethasone suppression test. PMID- 8353174 TI - Dopamine and depression: circuitous logic? PMID- 8353175 TI - Mouse preimplantation embryos exhibit receptor-mediated binding and transcytosis of maternal insulin-like growth factor I. AB - High-resolution microscopy in conjunction with colloidal gold-labeled insulin like growth factor I (IGF-I) has been used to provide evidence that the IGF-I receptor is first detected in 8-cell-stage mouse embryos, confirming the results of previous reverse transcriptase polymerase chain reaction (RT-PCR) studies. Specificity for the IGF-I receptor was demonstrated by displacement with unlabeled IGF-I and dual-labeling experiments with colloidal gold-labeled or unlabeled insulin. Labeled IGF-I ligand is internalized by means of receptor mediated endocytosis following its concentration in coated pits, and it can be visualized within cytoplasmic organelles. Immunocytochemical analyses at the blastocyst stage, using gold-labeled antibodies to the receptor, confirmed the expression of IGF-I receptors on all cells of the embryo. Similar studies with antibodies directed against the ligand demonstrated that IGF-I internalized by the embryo in vivo is maternally derived. Approximately 40% of blastocysts showed apical plasma membrane binding of gold-labeled ligand ("responders"), while approximately 60% did not demonstrate binding ("nonresponders"); however, both classes of embryo expressed receptors on basolateral membranes of trophectoderm cells and on the surface of inner masses. Functional studies show that incubating embryos in physiological levels of IGF-I (40 ng/ml) results in increased numbers of cells in the inner cell mass (p < 0.05), but not the trophectoderm, as compared to controls. PMID- 8353176 TI - Hyperosmotic tolerance of human spermatozoa: separate effects of glycerol, sodium chloride, and sucrose on spermolysis. AB - Hyperosmotic stress, which cells experience during the freezing process, and its release during the warming process are both related to cryoinjury. To define optimal cooling or warming rates and prevent osmotic injury to human sperm, information is required regarding the osmotic tolerance of the cells as a function of 1) time, 2) temperature, 3) type of solute, and 4) solute concentration. Human sperm samples were divided into three aliquots. The aliquots were equilibrated at 0, 8, and 22 degrees C, respectively. Different hyperosmotic solutions were prepared by addition of either a permeating cryoprotective agent (glycerol) or nonpermeating solutes (sucrose, non-ionic; or NaCl, ionic) to isotonic Mann's Ringer solution. Aliquots of the prepared solutions were equilibrated at 0, 8, and 22 degrees C, respectively. A small volume (2.5 microliters) of each sperm aliquot was quickly mixed with 50 microliters of each hyperosmotic solution at the corresponding temperature. After times ranging from 5 s to 5 min, 10 microliters of each hyperosmotic cell suspension was abruptly returned to an isosmotic environment by mixing with 500 microliters of Mann's Ringer solution at the corresponding temperature. The plasma membrane integrity of cells after exposure to hyperosmotic stress and after return to isosmotic conditions was measured by a dual staining (carboxyfluoroscein diacetate and propidium iodide) technique and flow cytometry. The morphology of the treated cells was observed by scanning electron microscopy of freeze-substituted sperm. The results indicate that human spermatozoa exhibited a significant posthypertonic lysis/injury, i.e., loss of membrane integrity, when returned to isosmotic conditions after exposure to hyperosmotic solutions of NaCl or sucrose. The higher the hyperosmolality, the more serious the cell injury. The majority of the cells (> 50%) lost membrane integrity when the osmolality was > or = 2000 mOsm. In contrast, if the sperm were not returned to isosmotic conditions, the majority of the sperm in the hyperosmotic solutions appeared to maintain membrane integrity. For a given higher hyperosmolality (> 1000 mOsm), posthypertonic spermolysis was reduced with a decrease of temperature. Cell survival was also affected by time of cell exposure to hyperosmotic environments before cells were returned to the isotonic condition. The shorter the time, the higher the cell survival. When exposed to hyperosmotic glycerol solutions that were isotonic with respect to electrolytes, few cells lost their membrane integrity if the osmolality of glycerol was < 3000 mOsm. For a fixed high osmolality (> 3000 mOsm), the lower the temperature, the higher the percentage spermolysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8353177 TI - Effects of growth factors and growth factor-extracellular matrix interactions on mouse trophoblast outgrowth in vitro. AB - A variety of cell types at the blastocyst implantation site produce growth factors that could play important role(s) in the implantation process. Recent evidence indicates that decidual cells and/or embryos produce transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and colony-stimulating factor (CSF 1). Furthermore, receptors for EGF, PDGF, and CSF-1 have been detected on embryonic and trophoblastic cells. The purpose of this study was to investigate the effects of these growth factors and possibly growth factor-extracellular matrix interactions on mouse blastocyst attachment and trophoblast outgrowth in vitro. Various dilutions of the growth factors TGF-alpha, EGF, PDGF, FGF, and CSF 1 were added to cultures of 5-day-old hatched blastocysts in fibronectin-coated plastic wells. Blastocysts were scored for attachment, trophoblast outgrowth, and surface area at 24, 48, and 72 h. Each of these growth factors significantly enhanced trophoblast outgrowth, and a cocktail containing all of the growth factors had a significantly stronger effect. PDGF and FGF, but no other growth factors, also enhanced trophoblast outgrowth following pulsatile incubation with the fibronectin matrix coating of the culture wells, indicating that interactions between these growth factors and extracellular matrix elements could influence implantation. This study suggests that various growth factors may play an important role in the implantation process, that synergistic effects may be obtained by combinations of growth factors, and that interactions between certain growth factors and extracellular matrix elements may be significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353178 TI - Mullerian inhibiting substance production associated with loss of oocytes and testicular differentiation in the transplanted mouse XX gonadal primordium. AB - The mouse XX gonadal primordium develops seminiferous-like tubules after transplantation into the renal subcapsular site of the adult male or female mouse. We examined the ontogeny of Sertoli cell differentiation in XX gonadal grafts by immunocytochemical staining and organ culture bioassay for Mullerian Inhibiting Substance (MIS). During normal in situ development of the XY gonad, MIS staining was first detected in fetal Sertoli cells at 12 days of gestation (d.g.) and remained intense until 4 days postpartum (d.pp.), after which it gradually diminished with progressive testicular development. In the normal in situ XX gonad, MIS was detected in granulosa cells of growing follicles at 7 d.pp. and thereafter. When the XX gonad at 12 d.g. was grafted beneath the renal capsule, a few testicular cords composed of MIS-positive cells appeared on Day 7 post-transplantation (equivalent to 19 d.g.), much earlier than the normal appearance of MIS production in the intact XX ovary. The ovarian region containing germ cells at the meiotic prophase was unstained for MIS in the same sections. The incidence of XX gonadal grafts containing MIS-positive testicular cords and the number of such cords per gonadal graft steadily increased from Day 7 to Day 14 post-transplantation. Germ cells were absent or scarce inside the MIS positive testicular cords. The MIS bioactivity in both control gonads and gonadal grafts coincided with the immunocytochemical staining for MIS. These results support the hypothesis that XX cells differentiate into Sertoli cells as a consequence of oocyte loss in the gonadal graft. PMID- 8353179 TI - Zona pellucida filtration of structurally abnormal spermatozoa and reduced fertilization in teratospermic cats. AB - Zona pellucida (ZP) penetration, in vitro fertilization, embryo development, and the morphology of fertilizing sperm were examined through use of normospermic (> 60% structurally normal sperm/ejaculate) versus teratospermic (< 40% structurally normal sperm/ejaculate) ejaculates from domestic cats. In addition, the effect of swim-up processing on sperm-oocyte interaction was compared with that of simple sperm washing. Normospermic and teratospermic ejaculates were evaluated for sperm motility and morphology. Sperm were preincubated for 1 h, then coincubated with in vivo-matured follicular cat oocytes (n = 401) for 20 h and with ZP-intact, salt-stored oocytes (n = 202) for 6 h. In vivo-matured oocytes were assessed for percent cleavage and stage of embryo development over time. Salt-stored oocytes were assessed for percent ZP penetration (proportion of oocytes containing sperm within or through the inner ZP), mean (+/- SEM) number of inner ZP-penetrated sperm, and the morphology of all bound and penetrated sperm. The incidence of pleiomorphic sperm in raw ejaculates averaged 29% in normospermic versus 67% in teratospermic males, but all ejaculates contained high sperm motility ratings (> 60%). Swim-up processing increased (p < 0.05) the number of normal sperm recovered/teratospermic inseminate (66.5 +/- 2.3%) compared to recovery after simple washing (28.6 +/- 2.2%). Percent sperm motility also increased (p < 0.05) in teratospermic males after swim-up (90.0 +/- 1.3%) as compared to sperm washing (64.2 +/- 3.7%). Cleavage rate in vitro was higher (p < 0.05) using sperm from normospermic (86.3%) compared to teratospermic (50.3%) males, but rates of embryo development to the morula/blastocyst stage were similar (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353180 TI - Serotonergic 5HT2 receptors mediate the inhibitory action of serotonin on luteinizing hormone secretion in ovariectomized, estradiol-treated ewes that are refractory to short days. AB - Previous studies with high doses of cyproheptadine suggested that serotonergic (5HT) neural mechanisms participate in the photoperiodic inhibition of secretion of LH in ovariectomized estradiol-treated ewes. In the present study, we tested this hypothesis further with lower doses of more specific 5HT2 receptor antagonists, including the highly specific ketanserin. Eight ovariectomized estradiol-treated ewes were subjected to 90 long days (16L:8D) followed by 207 short days (8L:16D) in order to induce photorefractoriness. Plasma LH concentrations were measured in blood sampled twice weekly. Changes in LH pulse frequency were measured after intrajugular injections of cyproheptadine or ketanserin (0.1, 0.25, 0.6, and 1.5 mg/kg) before the increase in LH secretion induced by the short days (SD ewes). After the ewes became refractory to short days (RSD ewes), they were again treated with the three lowest doses of cyproheptadine and ketanserin and, in addition, methysergide at the same doses. In the period following the transition from long to short photoperiod, LH secretion increased above basal levels after 42.0 +/- 0.0 days (mean +/- SEM) and then decreased after 137.0 +/- 7.4 days. In SD ewes, cyproheptadine significantly increased the number of LH pulses at the lowest dose tested (0.13 vs. 1.13 pulses/3 h at 0.1 mg/kg). Similar responses were observed at 0.25 mg/kg (0.13 vs. 0.88 pulses/3 h), at 0.6 mg/kg (0.13 vs. 0.75 pulses/3 h) and at 1.5 mg/kg (0.13 vs. 0.88 pulses/3 h). Ketanserin induced a dose-dependent increase in the number of LH pulses at 0.6 mg/kg (0 vs. 0.63 pulses/3 h) and at 1.5 mg/kg (0 vs. 0.75 pulses/3 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353181 TI - Effects of corticotropin-releasing hormone on luteinizing hormone, testosterone, and cortisol secretion in intact male rhesus macaques. AB - We previously have shown that 6 h of restraint stress in intact male rhesus macaques (Macaca mulatta) suppresses plasma levels of both LH and testosterone and that this effect lasts beyond the period of restraint. Since corticotropin releasing hormone (CRH) inhibits both the GnRH pulse generator and LH release in ovariectomized macaques and is generally thought to be the central mediator of stress-induced inhibition of gonadotropin release, we investigated the influence of CRH administration on LH and testosterone in unrestrained intact male rhesus macaques. Blood samples were collected from 5 intact male macaques at 15-min intervals for 15 h from a remote site. During this time, each animal received a 4 h infusion of CRH (100-micrograms bolus followed by 100 micrograms/h for 4 h) through an indwelling jugular catheter. Blood samples were collected for an additional 8 h after cessation of the CRH infusion. ACTH and cortisol levels were significantly elevated during and after the CRH infusion and were comparable to levels observed during restraint. Although LH levels appeared lower in animals given CRH, they were not different from those in untreated control males. In some animals, CRH appeared to stimulate or prolong LH release. Testosterone levels in CRH-treated animals were significantly lower than in controls both during and after CRH administration. In some instances, increases in plasma LH were not accompanied by a rise in testosterone. This would suggest that as was observed in restrained animals, stress exerts either a direct or an indirect inhibition of testicular testosterone secretion. The present data indicate that this effect may be mediated by CRH. PMID- 8353183 TI - Identification and partial characterization of an immunoglobulin A protease associated with human sperm. AB - The ability of human sperm to evade local humoral immune response at the female genital tract has received little attention. As some microorganisms inactivate secretory immunoglobulin A (S-IgA) by enzymatic degradation as a part of their pathogenic mechanism, we decided to test the hypothesis that there is an IgA protease in human semen that helps sperm to progress through the cervix uteri. Incubation of different semen fractions in the presence of S-IgA revealed IgA protease activity associated with raw semen or sperm but not with seminal plasma; raw semen and sperm produced two split products of 66 kDa and 45 kDa, respectively, in SDS-PAGE. The enzymatic activity was blocked with EDTA. IgG and IgM were not digested under the same experimental conditions. Degradation of S IgA by an IgA protease on the sperm surface may be among the mechanisms present in semen that enable sperm to evade an immune response in the female genital tract. PMID- 8353182 TI - Purification and partial characterization of relaxin and relaxin precursors from the hamster placenta. AB - Previous immunological studies have indicated that the molecular structure of hamster relaxin is quite different from that of porcine relaxin. In the present study, hamster relaxin was purified from placentas and characterized in order to investigate its biochemical properties. Placentas from Days 14 and 15 of gestation were homogenized in 0.26 N HCl-62.5% acetone containing protease inhibitors. After centrifugation, soluble proteins were acetone precipitated. Soluble proteins were applied to a carboxymethyl cellulose ion-exchange column and bound proteins were eluted with 0.1 and 0.3 M NaCl. Western blot analysis detected 16.5-, 18.7-, and 36.0-kDa relaxin-immunoreactive (IR) proteins within the 0.1 M NaCl eluant and detected a 5.6-kDa relaxin-IR protein within the 0.3 M NaCl eluant. The 5.6-kDa protein was purified to homogeneity by gel filtration (Sephadex G-50), ion-exchange HPLC, and C18-HPLC. Reduction of the 5.6-kDa protein prior to electrophoresis resulted in a single band of lower molecular mass, suggesting that hamster relaxin consists of two chains of approximately equal molecular mass. Isoelectric point of the 5.6-kDa protein was 7.78. The 16.5 and 18.7-kDa IR proteins were copurified by gel filtration and ion-exchange HPLC. At least five isoelectric point variants were observed for the 16.5- and 18.7-kDa proteins. The N-terminal amino acid for the 5.6 and 18.7 relaxin-IR proteins was arginine, and subsequent cycles indicated an identical partial sequence that was consistent with that for relaxins from other species. PMID- 8353184 TI - Nuclear status of human sperm cells by transmission electron microscopy and image cytometry: changes in nuclear shape and chromatin texture during spermiogenesis and epididymal transit. AB - Computer-assisted transmission electron microscopy (TEM) image cytometry was used to investigate changes in nuclear shape and chromatin texture of human sperm during normal spermiogenesis and epididymal transit. Analysis was performed on a large series of micrographs of longitudinal sections of nuclei from spermatids and epididymal caput and cauda sperm. Thirteen parameters characterizing nuclear shape and chromatin texture were measured. Quantitative data showed that from early spermiogenesis to the end of epididymal transit, a decrease in nuclear area and width occurred concomitantly with not only an increase in chromatin condensation but also an increase in heterogeneity of the degree of condensation. The oriented spatial arrangement of chromatin along the major nuclear axis as measured by gradient parameters indicated that in humans, condensation of chromatin begins in the posterior pole and proceeds apically; this is an important difference between humans and other mammalian species. Most parameters did not differ substantially in sperm from testis and caput epididymis, but did change as the cells moved from the caput to the cauda epididymis, indicating completion of nuclear maturation. Discriminant functions of basic parameters, as followed by canonical transformation and cluster representation, automatically classified the nuclei in a sequence that was found to concur with the biological maturation sequence during normal spermiogenesis and epididymal transit. PMID- 8353185 TI - Involvement of the central noradrenergic system in opioid modulation of luteinizing hormone and prolactin secretion in the pig. AB - The role of norepinephrine (NE) in the progesterone (P)-dependent endogenous opioid peptide (EOP) suppression of LH and prolactin (PRL) secretion in the pig was studied. Fifteen ovariectomized gilts treated with P (0.85 mg/kg b.w. i.m.) twice daily for 10 days were assigned, 5 gilts each, to the following treatment groups: 1) control, 2) AIMAX (N-methyl-N1[1-methyl-2-propenyl]1,2 hydrazinedicarbothioamide), and 3) anti-GnRH serum. On day 4 of P treatment, AIMAX (125 mg per 1.8 kg feed/day), previously shown to be an NE synthesis inhibitor, was fed daily for 7 days to group 2. On the last day of P treatment, group 3 gilts received an i.v. injection of anti-GnRH serum at 0800 h while Group 1 animals received an i.v. injection of serum collected from hypophysectomized gilts. Jugular blood samples were collected every 15 min for 9 h starting at 1000 h. All gilts received two injections of naloxone (NAL; 1 mg/kg b.w., i.v.) at 1400 h and 1600 h and an injection of a GnRH analogue (D-[Ala6-desGly-NH10] ethylamide; 5 micrograms/pig, i.v.) at 1800 h. Pretreatment serum LH concentrations were lower (p < 0.05) in AIMAX-treated gilts (0.19 +/- 0.09 ng/ml) than in controls (0.53 +/- 0.09 ng/ml), but were similar to those in GnRH antiserum-treated gilts (0.32 +/- 0.09 ng/ml). NAL increased (p < 0.001) serum LH concentrations in control animals and averaged 1.6 +/- 0.2 ng/ml the first h. AIMAX and anti-GnRH serum blocked the NAL-induced LH secretion. Serum PRL concentrations averaged 6.0 +/- 0.1 ng/ml for all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353186 TI - Repeated administration of prostaglandin F2 alpha during the early luteal phase causes premature luteolysis in the pig. AB - Previous investigators considered pig corpora lutea refractory to the luteolytic effects of prostaglandin (PG) F2 alpha before Day 12 of the estrous cycle. This study was designed to determine whether multiple injections of PGF2 alpha would result in a sustained reduction of serum progesterone and luteolysis, leading to significant shortening of the estrous cycle and interestrous interval. On Days 5 10 of an estrous cycle, gilts (n = 4) received injections of 12.5 mg PGF2 alpha (dinoprost tromethamine) i.m. every 12 h, or vehicle (PBS; n = 4) according to the same schedule. Mean interestrous interval in PGF2 alpha-treated gilts was reduced (p < 0.001) to 13.3 +/- 0.5 days compared with 19.8 +/- 0.6 days for control gilts. Serum progesterone declined below 1 ng/ml by Day 10.5 in PGF2 alpha-treated gilts compared to Day 17.5 in control animals. Serum concentrations of estradiol-17 beta (E2) reached maximal levels in PGF2 alpha-treated gilts earlier (Day 12.5) in the cycle than in control gilts (Day 19.5). Peak E2 and LH concentrations coincided with the periestrous period, suggesting that PGF2 alpha induced estrus is accompanied by normal follicular development and ovulation. These results demonstrate that the pig is susceptible to the luteolytic effects of PGF2 alpha before Day 12 if repeated injections are given from Day 5 through Day 10. PMID- 8353187 TI - Progesterone regulation of endometrial estrogen receptor and cell proliferation during the late proliferative and secretory phase in artificial menstrual cycles in the rhesus monkey. AB - Progesterone (P) down-regulation of uterine estradiol (E) receptor (ER) appears to be a general mechanism by which P modulates E action in the uterus. Our present studies focus on the regulation of ER by P during the changeover from E to P dominance during artificial menstrual cycles in the rhesus monkey. Because of differential cell-type response and the cellular zonation of the primate uterus, we used immunohistochemical analysis in addition to biochemical assays to study the regulation of ER by P. Ki-67 immunoreactivity was used as an index of endometrial proliferation. We performed our analyses on Days 13 (peak of E), 14 (declining E and rising P), 17 (basal E and rising P), and 21 (basal E and peak P). ER immunoreactivity was present throughout the endometrium in luminal and glandular epithelia and stromal fibroblasts on Day 13. As E was withdrawn and P rose on Day 14 there were few distinct changes in ER staining in stromal and epithelial cells. On Day 17, immunoreactive staining showed a distinct reduction for stromal cells in all zones. Although luminal epithelial cells showed a decrease in immunoreactivity on Day 17, zones II, III, and IV retained positive staining for ER in glandular epithelia. ER staining in stromal cells on Day 21 was similar to the pattern observed on Day 17, whereas epithelial cells in zones I, II, and III showed a reduction in staining. Glandular epithelia in zone IV maintained strong positive staining for ER on Day 21.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353188 TI - Development of rabbit zygotes cultured in protein-free medium with catalase, taurine, or superoxide dismutase. AB - The present study was designed to examine the influence of several potential antioxidants in a synthetic medium completely devoid of macromolecules. Antioxidants may be beneficial as additives to a synthetic medium because they could serve as scavengers of toxic free radicals in media lacking serum, serum albumin, or other macromolecules that may serve as scavengers in more complex media. Rabbit zygotes were cultured for 72 h at 39 degrees C in media containing varying concentrations of the anti-oxidants in a gas phase consisting of 5% CO2:95% humidified air. At 72 h embryo development was recorded, and embryos were fixed and stained with Hoechst 33342 DNA stain to facilitate counting of cells. In experiment 1, concentrations of catalase ranging from 250 to 1000 IU did not affect the proportion of zygotes developing into blastocysts or the cell number (p > 0.05). In experiment 2, 2.5-10 mM taurine increased the proportion of zygotes developing into expanding blastocysts (70-78% vs. 40% for controls) and increased cell number from 100 to 154-159 (p < 0.05). In experiments 3 and 4, superoxide dismutase was tested over a range of 100-2400 IU/ml. The response reached a plateau at 600 IU/ml, with positive responses in rate of embryo development and growth similar to that found with taurine in experiment 2. These studies indicate that culture of zygotes into blastocysts in a macromolecule-free medium with 5% CO2:95% air is substantially improved when agents that could serve as antioxidants are included. Other mechanisms of action are not excluded by these studies. PMID- 8353189 TI - Chorioallantoic placenta formation in the rat. III. Granulated cells invade the uterine luminal epithelium at the time of epithelial cell death. AB - Rat gestation sites were microscopically examined on Days 7, 8, and 9 of pregnancy to determine the fate of epithelial cells lining the uterine lumen mesometrial to the implantation chamber. This region of the uterine lumen and the mesometrial region of the implantation chamber comprise the site of chorioallantoic placenta formation. The fate of the uterine luminal epithelium was closely associated with a subepithelial accumulation and epithelial invasion of granulated cells (granulated metrial gland cells). On Day 7, mature granulated cells were not detected in the subepithelial stroma, and epithelial cells appeared healthy. On Day 8, when granulated cells began populating the subepithelial stroma and a few crossed the basal lamina, some epithelial cells degenerated in situ. On Day 9, when large numbers of granulated cells invaded the epithelium, large numbers of epithelial cells were displaced from their basal lamina and were degenerating. Degenerating cells were of two morphological types. One type conformed to the standard description of apoptosis; that is, cells rounded up, detached from their neighbors, and their nuclei fragmented, although other organelles remained intact. The other type of cell degeneration resembled apoptosis in some respects, but the cells were very electron-dense, adjacent cells often remained attached, membranous organelles including mitochondria were swollen, and nuclei did not fragment. Granulated cells are related to natural killer cells, cells that induce target cell apoptosis, and we suggest that granulated cells may be involved in uterine luminal epithelial cell death. The conceptus remained in an antimesometrial region of the implantation chamber during the times studied and did not come into direct contact with these epithelial cells. PMID- 8353190 TI - Removal of the olfactory bulbs modifies the gonadal responses to photoperiod in the lesser mouse lemur (Microcebus murinus). AB - The sexual activity of the lesser mouse lemur, unlike that of most living primates, is clearly dependent on photoperiod. Males responded to long daylengths (> 12 h light/day) by rapid testicular development and an increase in testosterone levels reaching 65.8 +/- 1.5 ng/ml (n = 12) after 3 wk of inductive photoperiod. Levels were maintained unchanged until 14 wk of exposure to long photoperiod, when spontaneous gonadal regression was observed. Under short daylengths, intact males exhibited regressed gonadal function with low plasma concentrations of testosterone: 5.4 +/- 1 ng/ml. To investigate the effect of olfactory bulb deprivation on gonadal responses to photoperiod, 12 males were bulbectomized (BX) during exposure to either long (n = 8, BX1) or short (n = 4, BX2) daylengths. In both groups of BX males, responses to long or short daylengths were maintained. However, the timing and the amplitude of gonadal responses to photoperiod were modified; BX males underwent a significant delay in testis development and also had reduced testosterone levels (53.3 +/- 2.3 ng/ml and 37.3 +/- 0.9 ng/ml for BX1 and BX2 groups, respectively). Moreover, BX males did not exhibit spontaneous gonadal regression after 14 wk of exposure to long daylengths, indicating that the photorefractory state did not appear, at least under our experimental conditions. In this primate, olfactory bulbs exert an important effect on the neuroendocrinological control of reproductive responsiveness to photoperiod. PMID- 8353191 TI - Immunosuppressive levels of glucocorticoid block extrauterine luteolysins in the rat. AB - Leukocytes, normal constituents of the corpus luteum, release prostaglandins (PGs), superoxide, and hydrogen peroxide (H2O2) upon activation. These products appear to mediate luteolysis, and it has been postulated that activated leukocytes serve a role in corpus luteum regression. Glucocorticoids prevent leukocyte infiltration and activation by inhibiting cytokine production, secretion, and action, and also inhibit eicosanoid synthesis. The objective of the present studies was therefore to assess whether glucocorticoid would influence luteal regression in the rat. Ovulation and pseudopregnancy were synchronized in prepubertal rats by gonadotropin treatment. In uterine-intact rats, functional luteal regression, assessed from serum progesterone levels, began on Day 10 and was complete by Day 14. Dexamethasone blocked luteal regression in uterine-intact animals when administered daily from early in pseudopregnancy for as long as treatment was continued (up to Day 17). Immunosuppressive effects of dexamethasone were evident in the inhibition of estrogen-induced infiltration of eosinophils, as shown by abrogation of estrogen induced uterine peroxidase activity, and high continuous levels of dexamethasone were necessary to block luteolysis. Hysterectomy extended luteal function by several days, with maintenance of maximal serum progesterone levels up to Day 12; but serum progesterone levels were reduced about 50% by Day 16 and completely depressed by Day 19. Dexamethasone treatment of hysterectomized rats from Day 12 until Day 15 or 18 blocked the decline in serum progesterone levels. Dexamethasone treatment did not block the decrease in serum progesterone levels induced within 24 h by PGF2 alpha in uterine-intact animals on Day 9 or in hysterectomized animals on Day 19.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353192 TI - Effect of bovine serum albumin concentration and source on sperm capacitation in the golden hamster. AB - Since virtually all experiments on sperm capacitation routinely include serum albumin in the culture media, the relative effect of BSA concentration on sperm capacitation was investigated. The fertile life of hamster sperm, as measured by the ability to penetrate the zona pellucida, decreased from 5 to 3 h as the concentration of BSA was increased from 3 to 18 mg/ml. To determine the extent of sperm capacitation in sperm populations that resulted in 100% penetration, the rate and timing of sperm penetration through the zona pellucida was determined. For each insemination, the rate of sperm penetration (%/min), the time when 50% of the eggs were zona-penetrated (T50), and the sperm capacitation index (T50/rate) were calculated. The extent of sperm capacitation as measured by all three parameters increased as the duration of preincubation or the BSA concentration was increased. The data on the duration of preincubation and the BSA concentration matrix indicated two properties of the effect of BSA on sperm capacitation: 1) the extent of sperm capacitation after the first hour of preincubation was independent of BSA concentration; and 2) when sperm were preincubated for two or more hours, the capacitating effectiveness of BSA was saturable; the saturating concentration of BSA decreased as the duration of preincubation increased. To determine whether the first hour of preincubation is independent of BSA, sperm were preincubated for 1 h without BSA and then 2 h with BSA. The extent of sperm capacitation of these sperm was equal to that of the 3-h control sperm; thus the first hour of capacitation is independent of BSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353193 TI - Effect of cumulus maturity on sperm penetration in the golden hamster. AB - The influence of the cumulus on gamete interaction was investigated in naturally and precociously ovulated eggs from superstimulated (eCG) hamsters. Inseminations were performed in which the absolute gamete ratio (sperm/egg) was held constant, but the relative gamete ratio (sperm x egg-1 x ml-1) was varied 10-fold. Sperm penetration to the perivitelline space was significantly higher at the higher relative gamete ratio, indicating that there is no chemoattractant in the cumulus and that gamete interaction in cumulus-intact eggs is a function of collision frequency, which varies according to the relative gamete ratio. The level of successful gamete interaction as a function of the relative gamete ratio was determined for naturally and precociously ovulated eggs. The level of sperm penetration reached saturation at a relative gamete ratio of 10(3.3) for naturally ovulated eggs and 10(4.0) sperm x egg-1 x ml-1 for precociously ovulated eggs. At suboptimal relative gamete ratios, there was no difference in the level of penetration between partially and fully capacitated sperm. These results indicate that the larger, more mature cumulus of naturally ovulated eggs is successfully penetrated at lower collision frequencies than the denser, less mature cumulus of precociously ovulated eggs. To determine whether the maturity of the cumulus affects the timing of sperm penetration, cumulus-free and cumulus intact eggs were inseminated at their optimal relative gamete ratios. The rate of sperm penetration of partially capacitated sperm was not different between cumulus-free and cumulus-intact eggs, regardless of ovulation method. However, the period of time between insemination and when half the eggs were penetrated (T50) was longer in cumulus-intact eggs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353194 TI - Glutathione concentration during maturation and after fertilization in pig oocytes: relevance to the ability of oocytes to form male pronucleus. AB - The present study examined the kinetics of glutathione (GSH) concentration during maturation and after fertilization in pig oocytes and its relevance to the ability of pig oocytes to form a male pronucleus after in vitro fertilization. The GSH concentration was significantly higher in pig oocytes matured in Waymouth medium than in pig oocytes matured in either modified (m) TCM-199 or mTLP media. The addition of 0.04-0.57 mM cysteine (CySH) to mTLP significantly increased both the GSH concentrations in oocytes matured in vitro and the rate of male pronucleus formation as compared to those in oocytes cultured in mTLP alone. When pig oocytes were cultured 12, 24, or 36 h in mTLP plus 0.14 mM CySH, their GSH concentrations were significantly higher than in uncultured oocytes. After fertilization, the GSH concentration in pig oocytes declined significantly. GSH concentrations in oocytes matured in vivo did not differ from those in oocytes matured in mTLP plus 0.14 or 0.57 mM CySH. The results indicate that 1) the composition of maturation medium affects the GSH concentration in pig oocytes; 2) the addition of CySH to maturation medium permits GSH synthesis by the pig oocytes; 3) GSH levels in pig oocytes change during maturation and after fertilization; and 4) GSH synthesis during oocyte maturation is an important factor for promoting their ability to form a male pronucleus after fertilization. PMID- 8353195 TI - [New opioids for anesthesia--do we need them?]. PMID- 8353196 TI - [Cardiac pacemakers and implantable cardioverter-defibrillators in the perioperative phase]. AB - Recent developments have changed the techniques and indications for different methods of temporary cardiac pacing. Temporary transvenous pacing involves endocardial right ventricular stimulation by a bipolar electrode, introduced directly via a vein, or through a "paceport" pulmonary artery catheter. A "multipurpose" pulmonary artery catheter permits both atrial and ventricular sensing and pacing. Noninvasive transcutaneous cardiac pacing is safe, fast, and easily applicable. However, pain and discomfort from cutaneous nerve or muscle stimulation may be intolerable for unsedated patients. Transoesophageal cardiac pacing is usually successful only for atrial stimulation, e.g., in sinus node bradycardia, but is not indicated in patients with impaired AV-conduction. In patients with implanted pacemakers, temporary cardiac pacing can both impair or improve the haemodynamic situation. Implanted pacemakers should always be checked following surgery involving electrocautery. Preoperatively, rate-responsive pacemakers should be re-programmed so as to avoid activation of the rate responsive function. Automatic implantable cardioverter-defibrillators should be deactivated to avoid delivery of inappropriate shocks. In patients with implanted epicardial patch electrodes, transthoracic defibrillation can be difficult with routine defibrillation protocols and may require positioning of the paddles on the lateral chest wall. However, emergency noninvasive transcutaneous cardiac pacing is possible in such patients with normal thresholds. PMID- 8353197 TI - [Quantifying pathological disorders of consciousness. Reliability criteria, aims, feasibility]. AB - Within a survey of coma scales we distinguish scales of clinical findings (Glasgow Coma Scale [GCS], Glasgow Liege Scale [GLS], Innsbruck Coma Scale [ICS], Comprehensive Level of Consciousness Scale [CLOCS]), grading tests (Vigilance Scale [VS], Funktionspsychose-Skala-B [FPBS-B]) and level-scales (Reaction-Level Scale [RLS-85], Munich Coma Scale [MCS]). With regard to the purpose we differentiate a classification of depth, the prediction of prognosis and the monitoring of changes. For the purpose of classification of depth, the RLS-85 because of its superior objectivity is preferable, but the GCS is of comparable validity and more widely used. The GLS differentiates the deeper states of coma better than either of these because brainstem-reflexes in cranio-caudal order are added. Within the prediction of prognosis all coma-scales have only limited validity and for the purpose of resource economy require additional criteria in the individual case. For the purpose of monitoring changes the level-scales primarily do not fit, the GCS is not sensitive enough. The Glasgow-Cologne-List is better suited; it is more than one-dimensional, but can be expressed through the GCS numbers for comparative purposes. The ICS is not widely used and the prognostic validity has not been proven to the same extent. The Glasgow-Cologne List could be amplified for the less severe disturbances of consciousness according to Price (32,33), and for the lower levels according to the GLS (2,3,4). In both cases the expense is slightly higher.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353198 TI - [Score systems in emergency medicine]. AB - Trauma scores are used in emergency medicine to classify the severity of injuries. Score systems are applied in science and epidemiological investigations in emergency and intensive care. Moreover, trauma scores are intended to support the decisions in triage and predict the prognosis of mortality. Scores are based on anatomicmorphological or physiological parameters by which the intensity of injury is graded and valued. Commonly used scores are the Injury Severity Score (ISS) and the Revised Trauma Score (RTS). The Glasgow Coma Scale (GCS) is a system that is used worldwide to classify neurologic deficiencies after injury of the brain. Trauma scores have a good prognostic potential by comparing large data bases of different patient groups. Individual prognosis of mortality by trauma scores in the routine of emergency medicine are rapid classification of the injury after trauma and early identification of critically ill patients. Score systems can support decisions and the training of emergency staff. Future studies should go into the grade of rehabilitation and the quality of life after trauma as a -possibly score-aided-prognostic parameter. PMID- 8353199 TI - [Regulation of energy metabolism by the type and amount of carbohydrate administration]. PMID- 8353200 TI - [New possibilities of parenteral nutrition by various administration forms of amino acids]. PMID- 8353201 TI - [Importance of fats as energy supply, membrane building blocks and immunomodulators in parenteral nutrition]. PMID- 8353202 TI - [Trace elements and electrolytes as binding element of intermediary metabolism]. PMID- 8353203 TI - [Early extubation after heart surgery interventions: pro]. PMID- 8353204 TI - [Early extubation after heart surgery interventions: contra]. PMID- 8353205 TI - [Quality control 100 years ago. "Narcosis statistics" by Gurlt from 1893]. AB - Even 100 years ago the problem of quality assurance in anaesthesia was investigated. In 1890 the German Society of Surgery decided to start "Multicenter Statistics on Surgical Anaesthesia." The project was headed by Ernst Gurlt, surgeon in Berlin. In 1893 he reported on the basis of 62 questionnaires on approximately 50,000 anaesthetic procedures, mostly performed with chloroform. 9 fatal chloroform cases led to a mortality rate of 1:4,275. On the other hand among 6,213 cases with ether anaesthesia there was no death. Gurlt strictly recommended the administration of ether, seconded by contemporaries such as Garre, Trendelenburg, Roux and Juillard. Gurlt's report includes as appendix detailed information on the administered anaesthetics, application techniques, premedication, fatal and non-fatal complications extracted from 18 of the analysed questionnaires. Gurlt's publication is an early document of quality assurance in Germany. PMID- 8353206 TI - [Septic shock with acute abdomen in idiopathic hemochromatosis]. AB - The case of a patient with abdominal crisis and shock without any discernible origin who died 36 hours after hospital admission despite maximal therapy is described. Gram-negative sepsis, peritonitis and haemochromatosis with hepatic siderosis was the post-mortem diagnosis. We consider spontaneous peritonitis arising from translocation of normal intestinal flora (E. coli) through the intact wall of the gut combined with the impaired ability of the reticulo endothelial system to remove endotoxin to be the causative factors. It is unknown whether the adrenal insufficiency due to siderophilic adrenal hypophysis and adrenal glands contributed to the fulminant course of the disease. Undiagnosed liver cirrhosis and especially haemochromatosis should therefore be included in the differential diagnostic considerations in patients presenting with these symptoms, and in whom no obvious cause for a septic focus can be found. PMID- 8353207 TI - Portrait of inequality. AB - America's children are stalked by race- and income-based inequities that demand our attention. Health care reform efforts that respect the needs of the entire child can diminish these inequities. Six prescriptions will help: universal early childhood education; comprehensive health and family life education; parental support; reinforcement of male responsibility; comprehensive school-based clinics; and opportunities for higher education. PMID- 8353208 TI - National health insurance: is this the answer for the poor and underserved? PMID- 8353209 TI - Health care reform: what it might mean to urban public hospitals. AB - Health care reform proposals may affect public hospitals in a number of ways. To insure that such proposals benefit the underserved communities within which public hospitals operate, reform initiatives should be evaluated against 10 criteria that emphasize prevention and primary care, community health education, cost control, tort reform, and community values. PMID- 8353210 TI - Health care for Nebraska's medically indigent. AB - In this study, several alternatives for the provision of health care to the medically indigent of Nebraska were analyzed quantitatively and qualitatively. These alternatives were: expansion of county medical assistance programs, state purchased health insurance policies, Medicaid expansion, revenue pool to redistribute charity-care losses, all-payer rate system, mandated employer purchased health insurance, and charity-care districts. Under four future scenarios, alternatives were ranked on the basis of program costs, a sensitivity analysis, and qualitative criteria. This analysis found that state-purchased health policies would result in lower program costs than either an increase in county assistance programs or employer-mandated health insurance. Medicaid expansion would reach fewer than one-third of the state's medically indigent. A revenue pool and all-payer rate system are the least costly alternatives but depend on the continuing good will of providers. PMID- 8353211 TI - Hawaii's near-universal health insurance--lessons learned. AB - To date, Hawaii is the only state to have implemented near-universal health insurance. The cornerstone of this program is the country's only requirement that employers provide health insurance for all employees who work at least 20 hours per week. Combined with low unemployment, voluntary modified community rating by health insurers, and expanded Medicaid and Medicare, this employer mandate has been part of a patchwork mechanism that insures upwards to 95 percent of the state's population. Indeed, by adding a state-sponsored gap group-insurance program, Hawaii may now insure in excess of 95 percent of its population. The program has generated good health outcomes, good consumer satisfaction, and relatively modest overall health care expenditures. But for all that near universal insurance provides, there is still a great need for community-based preventive and primary care programs with outreach and family support services. In addition, traditionally underserved populations continue to be at increased risk. Both funding reform and continued infrastructure development must occur to achieve universal access to care. PMID- 8353212 TI - The Oregon Health Plan: a rational approach to care for the underserved. AB - The Oregon Health Plan addresses the needs of 450,000 Oregonians presently without health insurance, among them 120,000 living in poverty who are not now Medicaid-eligible. This is accomplished by expanding eligibility for Medicaid to individuals and families with incomes at 100 percent of the federal poverty level. T0 help expand access within the limitations of the state budget, certain services, determined to be of limited value or effectiveness, are not covered for payment. This concept of rationing health care reimbursement stands in contrast to existing mechanisms of rationing employed by every state and the nation. The Oregon Health Plan introduces a rational plan for expanding services to the entire population of the state, while acknowledging the limitations of funding resources. PMID- 8353213 TI - Managed health care for Medicaid enrollees: the Philadelphia model. AB - HealthPASS, a program of capitated managed care for 82,000 Medicaid enrollees in a defined geographic area of Philadelphia, Pennsylvania, is administered by Healthcare Management Alternatives, Inc. (HMA), a minority-owned corporation, under a multiyear contract with the Commonwealth of Pennsylvania. HMA has striven to improve care to this low-income community by mounting innovative campaigns to encourage early access to health care, ongoing health education, and aggressive outreach and follow-up, in addition to specific projects designed to reduce infant mortality, expand Head Start, and bolster pediatric care. The program has been judged independently to provide high-quality service cost-effectively. PMID- 8353214 TI - Can a poor state afford not to expand Medicaid? AB - Some advocates of the uninsured support expansion of Medicaid programs, while others say that expansions are simply unaffordable, especially in poor states. State-level analyses of the costs and consequences of these expansion programs are infrequent. This study evaluates three programs to expand eligibility for Alabama's Medicaid program. The first two programs would raise the Aid to Families with Dependent Children (AFDC) eligibility threshold to 50 and 100 percent, respectively, of the federal poverty level. The third program, currently not available to the states without a federal waiver, would drop all categorical eligibility requirements and base eligibility solely on whether income is below the federal poverty level. Only 10.7 and 18.3 percent, respectively, of Alabama's uninsured would gain health care coverage under the first two programs. The third program would increase the proportion of Alabamians with health coverage to nearly 50 percent. For all of these programs, front-end state costs would be largely countered by federal funding and offsets, such as reductions in uncompensated hospital care and savings realized by former uninsureds from reductions in out-of-pocket expenditures for health services. PMID- 8353215 TI - How Tennessee finances Medicaid. AB - Tennessee is fortunate to have a comprehensive Medicaid program involving some 22 optional services, all financed through a combination of state revenues. These range from general state revenues to provider-donated funds, provider-specific taxes, and recently, a privilege tax. The state pays approximately $920 million to participate in Medicaid; the state's share generates $1.9 billion in federal dollars. The current system for financing the state's Medicaid program is unsustainable. Because Tennessee is relatively poor, legislators cannot afford to continue to increase its share of Medicaid expenditures at a rate 10 times greater than the general revenue increase from the entire state. To continue a comprehensive Medicaid program, Tennessee must move forward with alternative strategies to control Medicaid expenditures and manage resources. PMID- 8353216 TI - Principles of health care reform: an African-American perspective. AB - To protect the interests of underserved Americans, fair and rational health care reform must embrace 10 principles. These include universal and comprehensive coverage; mandatory cost containment; equity; freedom to change jobs or to relocate; high quality; reduced paperwork; primary care; help for the underserved; consumer-oriented care; and fair financing. PMID- 8353217 TI - Local advocacy for the medically indigent: strategies and accomplishments in one county. AB - Because no national health program assures entitlement to basic services, advocates must cope with barriers to access on the local level. The authors report several strategies that a community-based coalition has used to improve indigent care in one county. Research strategies have involved short-term investigations of barriers to needed services. Political strategies have attempted to improve the county government's administrative procedures and financial support of services for the poor. Legal strategies have involved the participation of attorneys who represent clients unable to receive care. Although such advocacy efforts do not guarantee access, they can substantially improve the availability of local services. PMID- 8353218 TI - National health care reform and community and migrant health centers. AB - Community and migrant health centers (CHCs) have been shown to increase access to health care, improve health status, and reduce health care costs in communities that they serve. Thus CHCs can play an important role in providing for underserved communities under any program of national health care reform whose aim is universal, affordable access. To benefit the poor, such a plan should be federally administered and progressively financed, with comprehensible enrollment procedures, easy paperwork, and clearly delineated limits and benefits. PMID- 8353219 TI - A proposal to provide care to the uninsured through a network of community health centers. AB - While a national health insurance plan is needed, this alone will not provide access for approximately 30 million persons who face geographic, cultural, language, or health care system barriers, or who live in areas with provider shortages. These barriers often coexist with lack of insurance coverage, but they also affect millions who have public, or even private, coverage. Moreover, large segments of this population suffer from health problems not adequately addressed by the traditional medical model: teenage pregnancy, AIDS, injury, substance abuse, and the like. To provide appropriate care for these underserved persons, we propose to expand the existing network of community health centers over the next 10 years to a total of approximately 3,000. Such an expansion would provide a cost-effective approach to improving provider distribution, increasing consumer input, combining personal health services with health promotion, and removing both financial and nonfinancial barriers to care. This model can be implemented either independent of or in conjunction with other health care system reform efforts. PMID- 8353220 TI - Targeting needs of the underserved: current programs in Tennessee. AB - Health care needs of indigents are a major force driving the need for health care reform in the U.S. Governor McWherter of Tennessee and his Administration have highlighted the need for available, affordable, and accessible health care services for all Tennesseans and especially for the medically indigent. This paper describes programs developed and implemented during the McWherter administration. These programs include community health agencies, placement of health care providers in underserved areas, increasing the number of citizens served by the Medicaid program, coordination of high-risk prenatal and child care to year one, and special demonstration projects in various African-American communities. Major reform is needed at the national level. In the meantime, the McWherter Administration will continue to develop new and innovative ways to increase the availability, accessibility, and affordability of health services in Tennessee. PMID- 8353221 TI - Improving access to the underserved through Medicaid managed care. AB - New York City's Harlem community faces extraordinary health care needs that a failing economy has made more urgent. In an attempt to open lines of access to health care, the New York City Health and Hospitals Corporation has implemented a managed care program for Medicaid participants. The program is a team approach to link each Medicaid patient with a primary care physician responsible for coordinating medical services for the patient. We hope the managed care program will help us conserve our dwindling resources while better managing patients' services and improving access to care. PMID- 8353222 TI - Children can't wait for health care reform. AB - There is widespread agreement that the American health care system needs comprehensive reform. This kind of reform will take time, however, and millions of Americans have urgent health care needs that must be met now. This is especially true for the nation's poor children, for whom the health care "safety net" has greatly eroded in the past decade. New Jersey's health care reform initiatives will ultimately provide for accessible preventive and primary pediatric care, with a community-based "medical home" serving as a child's gateway to the health care system. In the meantime, New Jersey has established programs dealing with such urgent problems as infectious childhood diseases, lead poisoning, AIDS, and infant mortality. While in the spirit of the state's long range planning effort, these programs are up and running now, their impact maximized in this period of budgetary constraints through coalition- and network building. PMID- 8353223 TI - Health care today: pragmatic reform or Utopia? PMID- 8353224 TI - What safety net for children? AB - As our nation attempts to address the multiple health and social needs of children, it is obvious that the so-called safety net of services for children and families is currently not meeting their needs. Within the current dialogue over health care reform, the special needs of children and pregnant women must not be lost. This paper discusses basic components which should be included in any discussion of health care reform. Individualized personal involvement in the solution to the health and social problems of today's underserved children and families is crucial. PMID- 8353225 TI - Health care reform for the elderly. Satellite teleconference. PMID- 8353226 TI - Principles for forging a national health plan. AB - One point which has emerged with a resounding voice during this conference is the need to clearly assemble and carefully communicate data and information as a means of empowerment. We hope that the recommendations from this conference will contribute to this end. We urge all to become actively involved in seeking change, and ensuring that the future health of Americans and of our nation will not reflect our inequitable, costly present. PMID- 8353227 TI - Diskitis in children. PMID- 8353228 TI - Role of infection due to Campylobacter jejuni in the initiation of Guillain-Barre syndrome. AB - Recent reports suggest that infection with Campylobacter jejuni, a common enteric pathogen, may cause Guillain-Barre syndrome (GBS) by triggering demyelination of peripheral nerves. GBS is preceded by an acute infectious illness (due to a variety of agents) in 50%-75% of cases; the onset of neurological symptoms is preceded by diarrhea in 10%-30% of cases. In the last decade, more than 20 published anecdotal reports and case series have described patients with C. jejuni infection documented 1-3 weeks before onset of GBS. Cultures of fecal samples obtained at the onset of neurological symptoms from patients with GBS have yielded C. jejuni in more than 25% of cases. A relatively rare serotype, Penner type O19, is overrepresented among isolates of C. jejuni from Japanese patients with GBS. Serological studies suggest that 20%-40% of patients with GBS have evidence of recent C. jejuni infection. In summary, infection with C. jejuni is a common antecedent to GBS and probably plays a role in initiating demyelination; although several pathogenic mechanisms are possible, none has been proven. PMID- 8353229 TI - Clostridium difficile infection associated with antineoplastic chemotherapy: a review. AB - Colitis and infection due to Clostridium difficile have been reported in patients receiving antineoplastic chemotherapy for cancer without prior antibiotic treatment. Chemotherapeutic agents can alter the normal bowel flora and cause extensive intestinal inflammatory changes, potentiating both the growth of C. difficile and its production of toxin. This review includes all 23 known reported cases of C. difficile infection associated with antineoplastic chemotherapy and examines the pathogenesis, clinical features, and management of this condition. Chemotherapy-associated C. difficile colitis has been documented in association with a variety of neoplasms. Various classes of antineoplastic agents have been incriminated, methotrexate most commonly. A spectrum of illness ranging from mild to fulminant has been reported. Symptoms, management, and outcome have appeared to be no different than for antibiotic-associated cases, but the available data are limited. Chemotherapy-associated infection with C. difficile may be underreported because it is not suspected and/or because frequent concomitant use of antibiotics masks its true incidence. C. difficile infection should be kept in mind whenever a patient undergoing antineoplastic chemotherapy develops diarrhea. Prompt, appropriate diagnostic testing and early treatment may avert morbidity and death. PMID- 8353230 TI - Mixed cutaneous phaeohyphomycosis in a cocaine user. AB - The dematiaceous fungi rarely cause serious disease in humans. We report a case of mixed cutaneous phaeohyphomycosis caused by two dematiaceous fungi, Exserohilum rostratum and Curvularia species, and review the microbiological characteristics and clinical significance of these organisms. PMID- 8353231 TI - Emergence of resistance to imipenem in Enterobacter isolates masquerading as Klebsiella pneumoniae during therapy with imipenem/cilastatin. AB - Clinical isolates identified as Klebsiella pneumoniae by the Vitek, Enterotube II, and API 20E systems were recovered from a patient undergoing therapy with imipenem/cilastatin. These isolates were resistant to multiple beta-lactam agents, and some were even resistant to imipenem. Analysis revealed a Bush group 1 beta-lactamase, and imipenem resistance corresponded to the loss of outer membrane proteins in strains expressing high levels of this beta-lactamase. Further characterization efforts yielded abnormal but positive results of tests for ornithine decarboxylase production and motility, and chromosomal homology to an Enterobacter cloacae ampR, ampC probe was detected. These results suggested that the organisms were actually of an Enterobacter species, perhaps Enterobacter aerogenes. Cefoxitin resistance may be a useful marker for preventing this misidentification in the future; misidentification of such organisms poses a hazard, as it may lead to inappropriate beta-lactam therapy for infections caused by organisms that have the potential for resistance due to inducible group 1 cephalosporinases. PMID- 8353232 TI - Forty years of meningococcal disease in Israel: 1951-1990. AB - Meningococcal disease accounts for approximately 20% of cases of bacterial meningitis in Israel. During the period 1951-1990, the annual incidence of meningococcal disease rarely exceeded two cases per 100,000 persons and was generally higher among non-Jews (largely the Arab population) than among Jews; there were some notable peaks of disease activity during 1963-1967, 1975, and 1987-1988. The highest incidence was among infants and young children, with a slight male predominance. The main period of disease activity was from January to April, but an unusual secondary peak in July coincided with the onset of peak summer temperatures. Monthly disease frequencies were significantly correlated with relative humidity. Incidence rates varied between regions and were lower in cities than in smaller settlements. Overall case-fatality rates decreased to approximately 11% for the period 1981-1990. Outbreaks were infrequent and tended to be small. Meningococci of serogroup B have dominated since the mid-1970s. Group A meningococci were isolated significantly more commonly from Arabs (26.26%) than from Jews (1.03%; P < .000001). The frequency with which group A organisms occurred among clinical isolates appeared to follow a more or less cyclical pattern. PMID- 8353233 TI - Cholecystitis caused by Campylobacter jejuni. PMID- 8353234 TI - A case of pelvic inflammatory disease associated with Neisseria meningitidis bacteremia. PMID- 8353235 TI - Multiple-drug-resistant Salmonella typhi. PMID- 8353236 TI - Invasive disease caused by multiple clones of Corynebacterium diphtheriae. PMID- 8353237 TI - Successful antepartum treatment of listeriosis with vancomycin plus netilmicin. PMID- 8353238 TI - St. Louis encephalitis in patients with human immunodeficiency virus infection. PMID- 8353239 TI - Potential interference of cycloserine in assay for cyclosporine. PMID- 8353240 TI - Fulminant sepsis due to group B beta-hemolytic streptococci following transcervical chorionic villi sampling. PMID- 8353241 TI - Clinical presentation and outcome in cases of listeriosis. PMID- 8353242 TI - Corynebacterium striatum: a diphtheroid with pathogenic potential. AB - Although nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize the skin and mucous membranes of humans, they rarely account for clinical infection. Corynebacterium striatum has rarely been reported to be a pathogen, causing pleuropulmonary infections and bacteremia in only immunocompromised or anatomically altered patients. We noted C. striatum to be the infecting pathogen or copathogen in six patients. To our knowledge, this report describes the first cases of C. striatum causing infection of exist sites of central venous catheters, thrombophlebitis associated with central venous catheters, conjunctivitis, and chorioamnionitis as well as a possible pathogen contributing to peritonitis and pyogenic granuloma. Unlike Corynebacterium jeikeium, which is highly resistant to beta-lactam agents, aminoglycosides, and quinolones, all strains of C. striatum isolated from the patients described in this report were susceptible to vancomycin and aminoglycosides, and all strains except one were susceptible to penicillin G, imipenem, and ciprofloxacin. C. striatum should be recognized as a potential pathogen in both immunocompromised and normal hosts in the appropriate circumstances, and appropriate antimicrobial therapy can quickly lead to resolution of infection. PMID- 8353243 TI - Group B streptococcal toxic shock-like syndrome: report of a case and purification of an associated pyrogenic toxin. AB - A patient with streptococcal toxic shock-like syndrome (TSLS) caused by Streptococcus agalactiae (group B Streptococcus) is described. The patient had all of the defining criteria for toxic shock syndrome (TSS), including fever, hypotension, erythematous rash, desquamation, and involvement of multiple organs. Neither Staphylococcus aureus nor group A streptococci were recovered, but vaginal and urine cultures yielded group B streptococci. The group B streptococcal isolate gave negative results in antibody tests for the production of TSS toxin 1, staphylococcal enterotoxins, and streptococcal scarlet fever toxins. However, the strain produced a novel pyrogenic toxin. This toxin, purified from culture fluids by ethanol precipitation, isoelectric focusing, and reverse-phase high-pressure liquid chromatography, had a molecular weight of 12,000 and an isoelectric point of approximately 7.0. The purified toxin was pyrogenic in rabbits, enhanced the susceptibility of the animals to lethal endotoxin shock, and caused the proliferation of rabbit splenocytes; these properties define pyrogenic toxins. When given to three rabbits via a subcutaneous miniosmotic pump, the toxin caused TSS-like symptoms ending in death. Three additional group B streptococcal strains from patients with TSLS were tested and were found to produce a toxin with similar properties. PMID- 8353244 TI - Toxic shock syndrome complicating influenza A in a child: case report and review. AB - Despite extensive literature on toxic shock syndrome, reports of its manifestations in children remain relatively uncommon. Similarly, toxic shock syndrome in association with influenza B or influenza-like illness has been reported in 12 patients, but it has been reported to occur following influenza A in only two patients to date. We report a third case of toxic shock syndrome in a child with influenza A and review the association between epidemic influenza and toxic shock syndrome ("the Thucydides syndrome"). PMID- 8353245 TI - Sustained bacteremia in 26 patients with a permanent endocardial pacemaker: assessment of wire removal. AB - We reviewed the data on 26 patients with permanent endocardial pacemakers who had 28 episodes of bacteremia to determine whether removal of the wire is required. Patients recovered completely from the first episode in seven of 20 cases of staphylococcal bacteremia and in six of six cases of nonstaphylococcal bacteremia (P = .015). Definitive cure was not achieved during the first episode in seven cases of staphylococcal bacteremia related to the pacing system when the wire was not withdrawn; however, cure was achieved in five of six cases when the whole pacemaker was removed (P < .01). The duration of treatment was longer for the patients from whom the wire was not removed during the first episode (P < .01). Whether cases of staphylococcal bacteremia were related to the pacing system or not, the rate of recovery of the responsible microorganism from the wires was similar for both groups of patients (six [82%] of seven and three [75%] of four, respectively). Nonstaphylococcal bacteremia was unrelated to the pacing system in five of six cases; these patients were all cured without removal of the wire. PMID- 8353246 TI - Visceral leishmaniasis in patients with AIDS: report of three cases treated with pentavalent antimony and interferon-gamma. AB - The optimal therapy for visceral leishmaniasis in patients with AIDS is unknown. We describe herein three patients with advanced AIDS and disseminated leishmaniasis who were treated with meglumine antimoniate plus interferon-gamma. The conditions of the three patients rapidly improved, and the therapeutic combination drastically reduced the parasite burden; after administration of antiprotozoal therapy for 4 weeks, cultures of bone marrow were negative for two of the three patients. Interferon-gamma was well tolerated. Because the patients died of other AIDS-related diseases in the months following therapy, the efficacy of the combination of meglumine antimoniate and interferon-gamma for preventing relapses remains unknown. PMID- 8353247 TI - Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 cases. AB - In this series of 31 patients with acute infection due to human immunodeficiency virus (HIV) type 1, the male-to-female ratio was 3.4:1 and the mean age was 31.3 years. Sexual transmission accounted for 83.9% of cases; 45.2% of the patients were homosexual and 38.7% were heterosexual. The mean duration of symptoms and signs was 21 days (range, 5-60 days). Fever (87.1%) and skin rash (67.7%) were most commonly reported. Physical examination findings were abnormal for 96% of the patients; the oral cavity (76.7%) and the skin (73.3%) were the most frequently involved sites. Thirteen of 25 patients with sexually acquired infection had genital or oral ulcers, whereas five intravenous drug users had none (P = .052). Thrombocytopenia was the most common hematologic abnormality and was detected in 17 of 23 patients tested. P24 antigenemia, an initially negative screening test for HIV antibody, and a low CD4+ lymphocyte count were noted in 23 of 29, 23 of 30, and 14 of 21 tested patients, respectively. PMID- 8353248 TI - Antibody to capsular polysaccharides of Streptococcus pneumoniae: prevalence, persistence, and response to revaccination. AB - The prevalence of immunity to Streptococcus pneumoniae in the adult population of the United States is unknown. In the study described herein, military recruits had anticapsular IgG antibody to only 15% of common pneumococcal serotypes, whereas working men and elderly men had IgG antibody to 33% and 34% of the common serotypes, respectively (P < .001). Among eight elderly subjects, the prevalence of IgG antibody to capsular polysaccharides increased from 30% to 78% after pneumococcal vaccination; 6 years thereafter, the rate of positive reactions had declined to 58% and IgG levels had declined substantially. With revaccination, IgG levels returned to within (+/-) 40% of the original postvaccination levels. IgM and IgG antibody appeared or began to increase in titer 6 days after vaccination; the rate and degree of response were the same after the first and second exposures. Since most individuals rapidly develop IgG antibody after colonization by S. pneumoniae and since IgG confers immunity, these data suggest that pneumonia is infrequent among healthy adults not because preexisting immunity is widespread but because--with colonization--an immune response develops rapidly, preceding specific events that might lead to infection. Our findings support recommended vaccination procedures and suggest that wider application in subsets of healthy younger adults should be considered. PMID- 8353249 TI - Mycobacterium avium complex infection and AIDS: advances in theory and practice. AB - The role of disseminated infection with the Mycobacterium avium complex (MAC) in the natural history of AIDS has been controversial. It is now clear that this complication of immunosuppression induced by human immunodeficiency virus type 1 (HIV-1) has a major impact upon the quality of life and duration of survival of patients with advanced HIV-1 infection. Progress has been made in our understanding of the bacteriology, pathogenesis, prevention, and treatment of MAC infection. Drs. Constance Benson and Jerrold Ellner (of Rush Medical College in Chicago and Case Western Reserve University in Cleveland, respectively) have led the effort by the AIDS Clinical Trials Group to develop new methods of managing this serious complication of advanced HIV-1 infection. In this AIDS commentary they review our current knowledge of MAC organisms and the clinical problems resulting from infection with these mycobacteria. PMID- 8353250 TI - Comparison of patients with enterococcal bacteremia due to strains with and without high-level resistance to gentamicin. AB - Patients with enterococcal bacteremia due to strains with and without high-level gentamicin resistance (HLGR; MIC, > 2,000 mg/L) were compared. Between 1986 and 1991, there were 178 episodes of enterococcal bacteremia: 47 and 131 episodes, respectively, due to enterococcal strains with and without HLGR. Sixty-two, 57, and 59 episodes, respectively, were in patients with transient bacteremia (a single positive blood culture), bacteremia (two or more positive blood cultures), and polymicrobial bacteremia. Nosocomial bacteremia accounted for 61.7% and 51.1% of episodes due to strains with and without HLGR, respectively. All isolates were strains of Enterococcus faecalis except for 13 strains of Enterococcus faecium, 4 of Enterococcus avium, and 3 of Enterococcus durans. Although the mortality was slightly higher among patients infected with strains with HLGR than among those infected with strains without HLGR (38.3% vs. 30.5%, respectively), there was no statistical difference. The mortality rate was adversely affected by old age (P < .01) and rapidly and ultimately fatal underlying conditions (P < .001). The addition of gentamicin to the treatment regimens had no effect on mortality. PMID- 8353251 TI - Intrapartum transmission of group A streptococcus. AB - Intrapartum transmission of group A streptococcus has not been well documented. As the incidence of severe infections due to this organism has recently increased, it is important to assess if such transmission occurs. We observed two cases of severe neonatal infections due to group A streptococcus, one of which was fatal, that appeared to have been transmitted from the mother during birth. Perinatal prophylaxis, which has been recommended for infections due to group B streptococcus, should be evaluated for infections due to group A streptococcus. PMID- 8353252 TI - Clinical algorithms for the screening of women for gonococcal and chlamydial infection: evaluation of pregnant women and prostitutes in Zaire. AB - A substantial proportion of women with gonococcal and/or chlamydial infection are asymptomatic. Thus active case detection is problematical, particularly in developing countries, where facilities and materials for laboratory testing are limited. We assessed the diagnostic validity of the hierarchical clinical algorithms recommended by the World Health Organization as well as that of a nonhierarchical scoring system, using data for 1,160 pregnant women (a low prevalence group) and 1,222 prostitutes (a high-prevalence group) in Kinshasa, Zaire. Neisseria gonorrhoeae and/or Chlamydia trachomatis was detected in 6.5% and 31.0% of pregnant women and prostitutes, respectively. No single variable that was both sensitive (> 60%) and specific (> 60%) was associated with infection. A simple hierarchical algorithm based only on reported symptoms had a sensitivity of 48.0% and 54.9% and a specificity of 75.2% and 52.2% for the screening of pregnant women and prostitutes, respectively. A second algorithm that included a speculum examination had a sensitivity of only 29.3% but a specificity of 85.3% in pregnant women. When a nonhierarchical scoring system was used, the sensitivity was 72.0% and 71.0% and the specificity was 73.5% and 55.8% for pregnant women and prostitutes, respectively. Scoring systems that incorporate risk markers as well as symptoms and signs may represent affordable alternative methods of screening for gonococcal and/or chlamydial infections among women in resource-poor settings. PMID- 8353253 TI - Efficacy of antimicrobial prophylaxis in placement of cerebrospinal fluid shunts: meta-analysis. AB - The objective of this study was to determine if perioperative antimicrobial prophylaxis decreases the incidence of subsequent shunt infection in patients who require placement of internal CSF shunts. Data sources included a computerized search of two biomedical data bases, contact with colleagues, and a review of abstracts of meetings and of references of identified trials and reviews. Studies were chosen for detailed review if they involved human subjects who underwent CSF shunt placement, with random allocation of patients to groups receiving perioperative systemic antimicrobial agents or to a control group and an outcome measure of subsequent shunt infection. Twelve (32%) of 37 studies met selection criteria and were included. Features of trial design were extracted and trial quality was evaluated with use of a predetermined protocol by three independent investigators who were blinded to titles, authors, and institutions. Individually, only one of 12 trials achieved statistical significance favoring prophylaxis; in the aggregate, the use of prophylactic antibiotics was associated with a significant reduction in subsequent CSF shunt infection (Mantel-Haenszel weighted risk ratio: 0.52; 95% confidence interval: 0.37, 0.73; P = .0002; approximate risk reduction: 50%). This systematic overview of 12 trials of 1,359 randomized patients demonstrates that perioperative use of antimicrobial agents in CSF shunt placement significantly reduces the risk of subsequent infection. PMID- 8353254 TI - [Magnetic resonance tomography (MRT) of the knee joint: meniscus, cruciate ligaments and hyaline cartilage]. AB - The use of MRT for diagnosing injury to the meniscus, the cruciate ligaments and hyaline cartilage was evaluated retrospectively in 82 knee joints without any knowledge of operative findings. In 49 cases the results were verified by arthroscopy and in 33 cases by arthrotomy. Sensitivity, specificity and diagnostic accuracy of MRT for meniscus lesions was 73.9%, 96.9%, and 94.6%. Corresponding values for lesions of the anterior cruciate ligament were 88.9%, 96.6%, and 94.7%, and for lesions of the hyaline cartilage 62.6%, 96.1%, and 87.9%, respectively. In addition to its high specificity, MRT proved accurate in excluding lesions of the meniscus (97.1%) of the anterior cruciate ligament (96.6%) and of hyaline cartilage (88.8%). A negative finding on MRT therefore makes the presence of a lesion of the meniscus, cruciate ligaments of cartilage unlikely. In such cases one is justified in delaying the use of arthroscopy or arthrotomy. PMID- 8353255 TI - [MRT in clinically unclear posttraumatic knee joint lesions]. AB - An MRI examination was performed on 31 patients with clinically questionable posttraumatic knee joint lesions. A broad range of intra- und extraarticular pathological changes was found. The correlation of MRI with arthroscopy and surgery showed a correct MRI diagnosis in 78% of the meniscal lesions (n = 18) and in 89% of the anterior cruciate ligament ruptures (n = 9). An analysis of false positive and false negative MRI diagnoses was made. MRI offers the opportunity for noninvasive complex assessment of knee joint structures and is of particular value in the diagnosis of posttraumatic knee joint lesions. PMID- 8353256 TI - [Bone marrow edema--an early form of femur head necrosis]. AB - We examined 15 patients (16 hips) with painful hips whose radiographs were either normal (n = 9) or showed a minimal decrease in radiodensity (n = 7). The available bone scintigrams of 9 cases were positive. T1-weighted images visualised a diffuse signal loss of the bone marrow in all hips, with various extensions in the head, neck, and intertrochanteric area. These regions were hyperintensive on T2-weighted images. Focal anomalies were not seen in any of the cases. All patients underwent core decompression treatment. Histology of 13 hips confirmed not only the presence of bone marrow oedema but of bone changes corresponding to those of avascular necrosis. Follow-up examinations with MR after core decompression showed normal signal intensity in all cases. Magnetic resonance represents a viable diagnostic tool for identifying bone marrow oedema. Due to our histological results bone marrow oedema should be included in the differential diagnosis as an early stage of necrosis of the hip. PMID- 8353257 TI - [Femur head necrosis and bone marrow edema syndrome in pregnancy]. AB - MR examinations were performed in 9 patients suffering from severe pain of the hip during the third trimenon without any relief after birth. Pathologic signal changes could be observed in 11 hips (oedema in the region of the femoral head and neck (n = 8); avascular necrosis of the femoral head surrounded by bone marrow oedema (n = 3)). In 7 hips a relatively rapid decrease of the oedema following core decompression was demonstrated. Focal necrosis, however, did not show any changes. In two patients, treated conservatively, markedly delayed healing was evident. MR imaging is the modality of choice for early diagnosis as well as follow-up of therapy of the bone marrow oedema syndrome or avascular necrosis and can be performed already during pregnancy. PMID- 8353258 TI - [The acetabular prosthesis: detection of a migration using ruler and pencil? Measurements on a pelvic phantom in comparison with a 3D computer simulation]. AB - Conventional X-ray films were made with varying degrees of tilt of a pelvic phantom containing an acetabular prosthesis. The position of the prosthesis was then reconstructed graphically. The measurement errors were calculated and an estimate was made for the tilt. There is a linear correlation between the measurement error and the tilt of the prosthesis. Therefore a tilt dependent maximum error can be calculated. This error is very small for small degrees of tilt, so that acetabular migration can in this instance be evaluated with greater confidence than with other graphical methods. The error also correlates with the determination of the selected region of the acetabulum, but not with the position of the central focus spot or image magnification. PMID- 8353259 TI - [The role of sonography and MR tomography in the diagnosis and therapeutic control of the carpal tunnel syndrome]. AB - 120 wrists of 105 patients with carpal tunnel syndrome were studied preoperatively by high-resolution sonography. Follow-up examinations after carpal tunnel release were performed in 72 wrists. In addition, 40 wrists were examined preoperatively, and 20 wrists were examined postoperatively by MR imaging. Based on quantitative analysis of the cross-sectional area and shape of the median nerve and of the palmar bowing of the flexor retinaculum, sonography established the diagnosis in 95% of cases. MR was superior in the evaluation of mild degrees of median nerve compression, and in the detection of possible causes of the carpal tunnel syndrome, such as synovitis of the flexor tendon sheaths or ganglionic cysts. In postoperative follow-up, sonographic demonstration of a normally flattened median nerve was an excellent indicator of the successful carpal tunnel release. In 10 patients with persistent or recurrent symptoms after carpal tunnel release, the underlying pathology could be exactly demonstrated by MR. PMID- 8353260 TI - [Diabetic osteoarthropathy (DO) of the forefoot]. AB - In patients suffering from diabetic osteoarthropathy, a total of 97 forefeet were evaluated concerning their bone tissue and soft tissue transformations. The most prevalent forms of demineralisation were circumscribed osteoporosis (21%) and diffuse osteoporosis (20%). Subluxations (6.2%), dislocations (2.1%), erosions (8.3%), marginal usures (11.3%) or cysts of the bone (11.3%) were seen only rarely. Extensions of the articular space (10.3%) were more prevalent than disappearances of the articular space (4.1%). The MTP (26.8%) and PIP joints (10.3%) were confirmed to be preferred localisations. A sudden loss of articular surface (25%) and a fast transition to mutilation (23.5%) show the increasing tendency of the fast transition to advanced stages of destruction by omitting the earlier stages. PMID- 8353261 TI - [99mTc-MAG3-kidney function scintigraphy without and with captopril in the diagnosis of renovascular hypertension]. AB - In this study, the diagnostic value of renal function scintigraphy performed both without and with ACE inhibition has been evaluated using the new radiopharmaceutical 99mTc-MAG3. In cases of decompensated renal artery stenoses, the typical scan finding with this tubular excreted agent was shown to be a distinct parenchymal nuclide retention in combination with a delayed appearance of the radiotracer in the pelvic system. Using this criterion in 43 patients with suspected renovascular hypertension, sensitivity and specificity were 89 and 88%, respectively. Bilateral positive findings were non-specific; excluding them from the study, specificity increased to 100%. In renal insufficiency, captopril scans seem to be of reduced diagnostic value. Summarising our experiences, renal function scintigraphy using 99mTc-MAG3 without and with captopril was proved to be a reliable non-invasive method to detect or exclude haemodynamically relevant renal artery stenosis. PMID- 8353262 TI - [The effectiveness of Braun's anastomosis in Billroth II surgery. The role of hepatobiliary sequence scintigraphy (HBSS) in the diagnosis of bile flow following stomach resection]. AB - After resection of the stomach the alkaline reflux of the duodenal contents into the residual stomach is a major factor to be taken into consideration when assessing the causes leading to irregularities of the mucosal barrier. Illnesses that may arise subsequent to gastric surgery are gastritis of the resected stomach, inflammation of the anastomosis, anastomotic ulcers and--with reservations--anastomotic carcinoma. In view of these clinical pictures, a protective function for the biliary system is ascribed to Braun's entero anastomosis. With the aid of hepatobiliary sequence scintigraphy (HBSS) a functional analysis was obtained from 30 patients, subsequent to gastric surgery- after Billroth II with entero-anastomosis--which showed a surprisingly high rate of reflux into the residual stomach, in 16 out of these 30 patients. The high grade HBSS data with regard to the biliary reflux proportions after gastric surgery and the low-grade effectiveness of Braun's entero-anastomosis are clearly evidenced. PMID- 8353263 TI - [Three-dimensional imaging of the pelvic veins using magnetic resonance angiography]. AB - The veins in the pelvis and lower limbs have been demonstrated by means of magnetic resonance angiography (MRA) in 11 normals and in 20 patients, using a "time-of-flight" technique (TOF). Using normals, changes in the measurement parameters were used in order to optimise the examination protocol; consequently, the internal and external iliac veins and the superior and inferior gluteal veins could be identified in all cases and the internal pudendal veins in 6 out of 11 cases. This examination protocol was then used in patients with clinical suspicion of lower limb or pelvic vein thrombosis. Comparison of the MRA findings with those of phlebography (7 cases), duplex sonography (6 cases) and colour Doppler examinations (11 cases) showed that MRA was better for diagnosing thrombosis of the internal iliac veins (10 cases) than the other methods. In two patients thromboses of the common iliac veins and the inferior vena cava were demonstrated which were missed by colour Doppler examination. On the basis of our present experiences, MRA, using a two-dimensional TOF technique, appears to be a reliable non-invasive technique for demonstrating the veins of the pelvis and thigh. PMID- 8353264 TI - [Magnetic resonance arteriography, duplex sonography and conventional arteriography for the evaluation of peripheral arterial occlusive disease]. AB - A prospective controlled study of 41 peripheral arterial occlusions was carried out, comparing duplex sonography, magnetic resonance arteriography and contrast arteriography. 87.8% of duplex sonography findings and 80.5% of magnetic resonance arteriographies agreed with the appearances of contrast arteriography (gold standard). Duplex sonography tended to overestimate the length of an occluded segment by an average of 2 cm (0.5-5 cm), whereas magnetic resonance arteriography showed less deviation from contrast arteriography (+/- 2 cm). The advantage of duplex sonography lies in its ability to provide morphological and functional information concerning the obliterated segment. Its disadvantage is that it can only demonstrate one segment and that the examination must be carried out in individual segments. Magnetic resonance arteriography provides vascular demonstration in several planes similar to angiography but signal-voids due to limited resolution and flow changes may limit diagnosis of occlusions. Additional phase contrast techniques may provide quantitative information on flow velocities and flow rates. Both duplex sonography and magnetic resonance arteriography are suitable methods for the non-invasive investigation of peripheral arterial occlusive disease. PMID- 8353265 TI - [Ambulant transbrachial 4-French arteriography with particular reference to the aortofemoral vascular system]. AB - Arteriograms were carried out on 176 patients using 4-F catheters through a transbrachial approach. Criteria for exclusion from the series were injuries to the upper limb, hemiparesis or poor pulses in the presence of a normal femoral pulse. There were no local vascular complications requiring treatment. On two occasions the brachial artery could not be punctured. Acute posterior cerebral infarction was the only serious complication (0.5%). 67% of the patients were examined on an outpatient basis and this did not appear to increase the risk of complication. We regard this as a suitable method for demonstrating the pelvic and lower limb arteries on ambulant patients. PMID- 8353266 TI - [Initial results of in vivo 31P-NMR spectroscopy of the spleen in patients with splenomegaly]. AB - In-vivo 31P-NMR spectroscopy of the spleen was carried out in 15 patients with splenomegaly from various causes (Hodgkin's disease, non-Hodgkin lymphoma, polycythaemia vera, chronic lymphatic leukaemia, chronic myeloid leukaemia). Volume selection was with the ISIS technique, voxel size was between 3 x 5 x 5 and 8 x 6 x 7 cm3. There was a markedly elevated (PM+Pi)/beta-NTP quotient (mean 3.41 with a standard deviation of 0.37) (p < 0.001) and raised PDE/beta/NTP quotient as compared with 8 normals, who showed an (PME+Pi)/beta-NTP quotient of 2.32 and a PDE/beta/NTP quotient of 1.11. These raised quotients were interpreted as indicating increased membrane phospholipid metabolism due to increased cell turnover. The data suggest there may be some clinical value in performing 31P-NMR spectroscopy for defining splenic involvement in myeloproliferative diseases but further confirmatory studies will be necessary. PMID- 8353267 TI - [Determinants of observer variability in early diagnostic mammography--a ROC analysis]. AB - As part of the German mammographic study, the participating doctors were given test films of 30 histologically confirmed cases. Regarding the indications for biopsy there was good sensitivity (the median amongst 25 doctors was 0.87). Specificity (median 0.86) could be improved. Comparison of individual results with the majority showed considerable variability within the group of doctors performing mammography. ROC analysis indicated that there was considerable observer variability which was independent from the specialty or praxis characteristics of the participants. The inclusion of mammography in an early diagnostic programme requires continuing education of the participants in this technique. This should be supported by further methods of quality assurance. PMID- 8353268 TI - [Percutaneous removal of an intraperitoneal foreign body]. PMID- 8353269 TI - [A functional disorder of the temporomandibular joint in a newborn infant- preoperative CT-3D diagnosis and postoperative documentation]. PMID- 8353270 TI - [Lymphoepithelial cyst of the tail of the pancreas--a case report]. PMID- 8353271 TI - Intramedullary spinal cord germinoma. Case report and review of the literature. PMID- 8353272 TI - A natural history for pediatric acute leukemia. PMID- 8353273 TI - Dynamics of GATA transcription factor expression during erythroid differentiation. AB - Although the formation of terminally differentiated erythroid cells has been shown to require the presence of a functional GATA-1 gene in vivo, the role of this transcription factor and other members of the GATA family at earlier stages of erythroid differentiation is unclear. In this report, the expression of GATA 1, GATA-2, and GATA-3 has been examined in enriched peripheral blood progenitors before and after culture in a well-characterized liquid culture system. In addition primary leukemic cells as well as several erythroleukemic and nonerythroid cell lines were analyzed for GATA factor expression. The results show that the profile of GATA factor expression in erythroid cells is distinct from that of myeloid or lymphoid lineages. Erythroleukemic cell lines express little or no GATA-3, but high levels of GATA-1 and GATA-2. When they are induced to display the terminal erythroid phenotype, little change in the level of GATA-1 is detected but a significant decline in the levels of GATA-2 is observed commensurate with the degree of maturation achieved by the cells. Enrichment of erythroid progenitors from peripheral blood leads to selection of cells that express both GATA-1 and GATA-2. As the enriched populations are cultured in suspension in the presence of multiple cytokines, the levels of both GATA-1 and GATA-2 initially increase. However, in cultures containing only erythropoietin, which show exclusive erythroid differentiation, the levels of GATA-1 continue to increase, whereas GATA-2 expression declines as erythroid maturation progresses. In contrast, cultures lacking Epo (ie, with interleukin-3 and kit ligand) display limited progression towards both the myeloid and erythroid pathways, and high levels of expression of both GATA-1 and GATA-2 are maintained. Despite the initial upregulation of GATA-1 expression in the latter cultures, terminal erythroid differentiation does not occur in the absence of erythropoietin. These results indicate that GATA-1 upregulation is associated with both the initiation and the maintenance of the erythroid program, but that these two processes appear to be under separate regulatory control. Thus, the dynamic changes in the levels of different GATA factors that occur during primary erythroid differentiation suggest that the levels of these factors may influence the progression to specific hematopoietic pathways. PMID- 8353274 TI - The chromosome 4q21 gene (AF-4/FEL) is widely expressed in normal tissues and shows breakpoint diversity in t(4;11)(q21;q23) acute leukemia. AB - The chromosomal translocation, t(4;11)(q21;q23), is the most common type of 11q23 chromosomal abnormality, being highly prevalent in infant acute leukemias and associated with a poor prognosis. The t(4;11) results in the fusion of an 11q23 gene (MLL, HRX, Htrx-1, or ALL-1) and a 4q21 gene (AF-4 or FEL). To further evaluate the 4q21 gene and its role in t(4;11) acute leukemia, we have cloned a 38-kb genomic region and mapped exons of the AF-4 gene. The 4q21 breakpoints in 19 cases of t(4;11) acute leukemia were analyzed by Southern analysis and pulsed field gels. Seventeen of the 19 cases had breakpoints on chromosome 4q21 that were scattered in this 38 kb region. Expression of the AF-4 gene was studied in a total of 28 various nonhematopoietic, hematopoietic, and t(4;11) leukemic cell lines. The AF-4 gene was expressed in all cell lines as a major and a minor transcript. In addition to the normal transcripts, two fusion transcripts from the derivative 11 and derivative 4 chromosomes were identified in all t(4;11) cell lines except B1, which had only the der(11) transcript. These findings suggest that the breakpoints on 4q21 cluster over a broader area than do the breakpoints in the 11q23 gene, and that der(11) encodes the fusion RNA found consistently in leukemia cells. PMID- 8353275 TI - Predictability of the t(1;19)(q23;p13) from surface antigen phenotype: implications for screening cases of childhood acute lymphoblastic leukemia for molecular analysis: a Pediatric Oncology Group study. AB - The t(1;19)(q23;p13) translocation occurs in approximately 5% of B-precursor acute lymphoblastic leukemias (ALLs) occurring in children. Its presence has been associated with a poor prognosis, which may be overcome with more intensive therapy. Although leukemic cells from cases of t(1;19)-ALL frequently express cytoplasmic mu heavy chains, their complete antigenic profile remains undefined. Among 697 consecutive cases of B-precursor ALL with complete phenotypic studies using a panel of monoclonal antibodies, 22 cases were found to carry the t(1;19). Twenty of 22 cases had an identical, complex phenotype characterized by homogeneous expression of CD19, CD10, and CD9; complete absence of CD34; and at least partial absence of CD20. Overall, this phenotype was seen in only 8.0% (56 of 697) of childhood B-precursor ALL. One of the two remaining t(1;19)-carrying cases conformed to this phenotype, but was lacking data for CD9. The other case differed by virtue of expression of CD34 and was also hyperdiploid with 55 chromosomes. Molecular studies showed E2A-PBX1 abnormalities in all examined cases (12 of 12) with the t(1;19), including the case lacking CD9 data. In contrast, no E2A-PBX1 abnormalities were detected in the sole t(1;19)-ALL with CD34 expression. Seventeen cases with the characteristic phenotype and uninformative cytogenetics were also molecularly analyzed and 5 of 17 (including 4 of 8 with unsatisfactory cytogenetics and 1 of 9 with a normal karyotype) contained E2A gene rearrangements and E2A-PBX1 fusion mRNAs. Our results show that all cases of t(1;19)-ALL with concomitant E2A-PBX1 fusion invariably express a characteristic but uncommon profile of surface antigens. These observations suggest that selective molecular analysis of a small subset of patients (those with uninformative cytogenetics and the characteristic phenotype) can identify a significant number of additional cases of ALL with E2A-PBX1 fusion that might benefit from more intensive therapy. PMID- 8353276 TI - Hematopoietic cells from mice deficient in wild-type p53 are more resistant to induction of apoptosis by some agents. AB - Wild-type p53 is a tumor-suppressor gene that can induce cell death by apoptosis when expressed in myeloid leukemic and some other types of tumor cells. However, the question remained as to what extent wild-type p53 is a mediator of apoptosis in normal cells. We have used mice deficient in wild-type p53 to determine whether induction of apoptosis in hematopoietic cells from these p53 deficient mice is defective. We show here that bone marrow myeloid progenitor cells from p53-deficient mice are more resistant to induction of apoptosis when there was only a low concentration of the viability factors granulocyte-macrophage colony stimulating factor; interleukins-1 alpha, -3, and -6; or stem cell factor; or when apoptosis was induced in these cells by irradiation or heat shock. The loss of one allele of wild-type p53 was sufficient for increased resistance. The higher resistance to apoptosis in p53-deficient mice was also found in irradiated thymocytes, but not in thymocytes treated with dexamethasone or in mature peritoneal granulocytes. The degree of resistance in irradiated myeloid progenitors and thymocytes showed a dosage effect of the number of wild-type p53 genes. The results show that wild-type p53 is involved in the induction of apoptosis by some agents in normal hematopoietic cells. Loss of wild-type p53 can, therefore, contribute to tumor development by decreasing cell death at low concentrations of viability factors and after exposure to a DNA-damaging agent. The results also show that there are wild-type p53-dependent and -independent pathways of normal cell apoptosis. PMID- 8353277 TI - Home treatment with intravenous enzyme replacement therapy for Gaucher disease: an international collaborative study of 33 patients. AB - Intravenous enzyme replacement therapy (Alglucerase; Ceredase; Genzyme Corp, Boston, MA) is an effective and safe treatment for patients with type 1 Gaucher disease. In an attempt to reduce its high cost, a "low-dose high-frequency" protocol (30 U/kg/mo, 3 times a week) was introduced and found to be as effective as the original high-dose protocol (60 U/kg every 2 weeks). Because receiving frequent infusions creates a burden for many patients, we have implemented a program of home treatment for our patients. We now report the safety and feasibility of low-dose/high-frequency home intravenous enzyme-replacement therapy in 33 patients with Gaucher disease. The chronic nature of the treatment, its safety, lack of adverse effects, the stable condition of most patients, and the need to reduce the high cost make enzyme replacement for Gaucher disease a good candidate for intravenous home therapy. PMID- 8353278 TI - Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130. AB - The interleukin-6 (IL-6) signal is transduced through membrane-anchored gp130, which is associated with IL-6 receptor (IL-6R) in the presence of IL-6. Soluble forms of gp130 (sgp130) with molecular weights of 90 and 110 Kd were found in human serum. In the presence of recombinant IL-6 (rIL-6), serum sgp130 were capable of associating with serum sIL-6R. By the sandwich enzyme-linked immunosorbent assay, healthy human sera was shown to contain 390 +/- 72 ng/mL of sgp130. A mouse pro-B-cell line-derived transfectant, BAF-130, expressing human gp130 was used to examine the function of serum sgp130. When supplemented with rIL-6, human serum induced DNA synthesis in BAF-130 cells, whereas the serum deprived of sIL-6R did not. In contrast, the DNA synthesis induced in BAF-130 cells by rIL-6-supplemented serum was increased when the serum was deprived of sgp130. These results indicated that serum sgp130 could negatively regulate the IL-6 signal. Recently, gp130 has been shown to be involved in the signaling processes of oncostatin M, leukemia inhibitory factor, and ciliary neurotropic factor, in addition to those of IL-6. Recombinant sgp130 showed inhibitory effect on the biologic function of such cytokines. This work implies physiologic roles of naturally produced serum sgp130 in modulating signals through gp130. PMID- 8353279 TI - Prothymosin alpha gene expression correlates with proliferation, not differentiation, of HL-60 cells. AB - Accumulating evidence suggests that prothymosin alpha has an as yet undefined intracellular, perhaps intranuclear, function related to cell proliferation. Prothymosin alpha mRNA and/or peptide levels increase when cells are stimulated to proliferate. Because proliferation and differentiation events are often inversely correlated, we examined prothymosin alpha gene expression during proliferation and differentiation of HL-60 myeloid leukemia cells. Steady-state levels of prothymosin alpha mRNA, which are high in exponentially growing HL-60, decrease within hours after induction of HL-60 to differentiate along the neutrophil pathway with dimethylsulfoxide (DMSO) or along the macrophage lineage with either tetradecanoylphorbol acetate (TPA) or bryostatin 1. The decline in prothymosin alpha mRNA in response to these differentiation signals parallels that of c-myc mRNA under the same conditions. We then determined whether the downregulation of prothymosin alpha and c-myc mRNA were due to differentiation or cessation or proliferation. Recombinant human gamma-interferon induces monocytic differentiation of HL-60, but permits continued proliferation, and, under these conditions, expression of prothymosin alpha, as well as of c-myc, mRNA remains elevated. We conclude that prothymosin alpha and c-myc expression are coregulated in differentiating HL-60 and that their expression correlates with the proliferative state of HL-60 cells, rather than with the differentiated state. PMID- 8353280 TI - Enhancement of the biologic effects of interleukin-3 in vivo by anti-interleukin 3 antibodies. AB - Interleukin-3 (IL-3) has been shown to be a promising agent in the stimulation of bone marrow regeneration following myeloablative therapy. The biologic half-life of this agent is very short (5 to 15 minutes), which limits the effectiveness of low-dose therapy. Here we show that the biologic effects of low-dose IL-3 in mice may be enhanced by concurrent use of polyclonal anti-IL-3 antibodies. The biologic effects of IL-3 in vivo were enhanced dramatically by the combination of the cytokine and polyclonal rabbit anti-IL-3 antibodies, which recognized a peptide comprising the first 29 amino acids of the IL-3 molecule. Enhancing effects were not apparent in vitro, where weak neutralizing properties were observed for these antibodies. The mechanism of this enhancement by the antibody appears to be via a ninefold reduction in the total-body clearance of the cytokine in vivo. The apparent volumes of distribution for IL-3 and for the IL 3/antibody complex were surprisingly similar and exceeded the expected intravascular volume. The prolonged biologic half-life of IL-3 was reproducibly associated with a threefold to fivefold increase in splenic mast-cell precursors over levels observed in mice treated with IL-3 alone; increases in the numbers of mature mucosal-type mast cells in the spleen, but not in the jejunum or lung; increases in IL-3-dependent colony-forming unit-cell in the spleen; and an apparent redistribution of mast cells away from the bone marrow. These experiments demonstrate that antibodies to a cytokine can enhance the biologic activity of that cytokine in vivo. PMID- 8353281 TI - Regulation of manganese superoxide dismutase and other antioxidant genes in normal and leukemic hematopoietic cells and their relationship to cytotoxicity by tumor necrosis factor. AB - Myeloid cells are a major source of superoxide and other oxygen metabolites. As a protective mechanism, cells express antioxidant enzymes including manganese superoxide dismutase (Mn-SOD), copper-zinc SOD (Cu/Zn-SOD), and glutathione peroxidase (GSX-PX). Even though hematopoietic cells are a major source of oxidants, little is known of their expression of antioxidants. We found that seven myeloid leukemic cell lines blocked at different stages of differentiation constitutively expressed Mn-SOD, Cu/Zn-SOD, and GSX-PX RNAs. Level of Mn-SOD activities paralleled levels of Mn-SOD RNA. Terminal differentiation of native HL 60 cells to either granulocytes or macrophages did not alter levels of Mn-SOD RNA but markedly decreased cell division. Myeloid leukemic lines sensitive to cytotoxic effects of tumor necrosis factor (TNF) as well as normal peripheral blood lymphocytes and monocytes, dramatically increased their levels of Mn-SOD RNA in the presence of TNF. In contrast, Cu/Zn-SOD and GSX-PX RNA levels did not increase in these same cells. TNF-resistant leukemic lines had higher constitutive levels of Mn-SOD RNA and activity; and these levels did not change in the presence of TNF. Antisense but not random oligonucleotides to Mn-SOD markedly increased the sensitivity to the inhibitory effects of TNF for both the native HL-60 (TNF-sensitive) and K562 (TNF-resistant) cell lines. Further studies showed that the antisense oligonucleotides entered the cells and resulted in decreased levels of Mn-SOD RNA. The data suggest that Mn-SOD may provide protection against cytotoxicity of TNF in hematopoietic cells. PMID- 8353282 TI - Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency. AB - Homozygous or double heterozygous protein-C deficiency can present at birth with purpura fulminans or later in life with venous thrombosis. Two homozygous patients who had previously sustained thrombotic episodes were investigated at a time when they were asymptomatic and not receiving antithrombotic therapy. The plasma levels of protein-C antigen and activity in both individuals were approximately 20% of normal. We administered a highly purified plasma-derived protein C concentrate to these individuals and monitored levels of several markers of in vivo coagulation activation. Assays for protein-C activation (activated protein C and protein C activation peptide) showed a sustained increase from reduced baseline levels, whereas thrombin generation (as measured by prothrombin fragment F1 + 2) gradually decreased over about 24 hours into the normal range. These investigations provide direct evidence that protein C is converted to activated protein C in vivo, and that the protein-C anticoagulant pathway is a tonically active mechanism in the regulation of hemostatic system activation in humans. PMID- 8353283 TI - CD63 is a component of Weibel-Palade bodies of human endothelial cells. AB - Weibel-Palade bodies are secretory granules of vascular endothelial cells specialized in the storage of von Willebrand factor (vWF) and P-selectin, two adhesion proteins that can be rapidly mobilized to the cell surface by exocytosis in response to thrombin or other agonists. In this study, we attempted to identify additional components of Weibel-Palade bodies by raising monoclonal antibodies to these granules, purified by cell fractionation. One antibody, 2C6, was found to be specific for CD63, a membrane glycoprotein previously described in the lysosomes of platelets and other cell types. The immunopurified 2C6 antigen was recognized by an anti-CD63 reference antibody, 2.28, by Western blotting. Also, the biosynthetic profile of the 2C6 antigen in endothelial cells showed a nascent molecular mass and a glycosylation pattern identical to that of CD63. Immunofluorescence staining with 2C6 showed the lysosomes, and also elongated structures identified as Weibel-Palade bodies by their shape, distribution, and positive staining with anti-vWF antibodies, CD63 was also found by Western blotting of subcellular fractions highly enriched in Weibel-Palade bodies. Our results indicate that CD63 colocalizes with vWF and P-selectin in the Weibel-Palade bodies of endothelial cells, and together with these adhesion proteins it could be rapidly expressed on the cell surface in areas of vascular injury and inflammation. PMID- 8353284 TI - Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha in response to autologous tumor stimulation. AB - Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50% of cells (median) were malignant B cells and 36% were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75% +/- 8% CD3+ (mean +/- SEM), 47% +/- 8% CD4+ and 35% +/- 7% CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20% of patients studied. PMID- 8353285 TI - Reactive oxygen intermediates activate NF-kappa B in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the p56lck and p59fyn tyrosine kinases in human lymphocytes. AB - We have previously observed that ionizing radiation induces tyrosine phosphorylation in human B-lymphocyte precursors by stimulation of unidentified tyrosine kinases and this phosphorylation is substantially augmented by vanadate. Ionizing radiation generates reactive oxygen intermediates (ROI). Because H2O2 is a potent ROI generator that readily crosses the plasma membrane, we used H2O2 to examine the effects of ROI on signal transduction. We now provide evidence that the tyrosine kinase inhibitor herbimycin A and the free radical scavenger N acetyl-cysteine inhibit both radiation-induced and H2O2-induced activation of NF kappa B, indicating that activation triggered by ROI is dependent on tyrosine kinase activity. H2O2 was found to stimulate Ins-1,4,5-P3 production in a tyrosine kinase-dependent manner and to induce calcium signals that were greatly augmented by vanadate. The synergistic induction of tyrosine phosphorylation by H2O2 plus vanadate included physiologically relevant proteins such as PLC gamma 1. Although treatment of cells with H2O2 alone did not affect the activity of src family kinases, treatment with H2O2 plus vanadate led to activation of the p56lck and p59fyn tyrosine kinases. The combined inhibition of phosphatases and activation of kinases provides a potent mechanism for the synergistic effects of H2O2 plus vanadate. Induction of tyrosine phosphorylation by ROI may thus lead to many of the pleiotropic effects of ROI in lymphoid cells, including downstream activation of PLC gamma 1 and NF-kappa B. PMID- 8353286 TI - Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis. AB - Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially proteinase 3 (PR-3), have proved to be a useful clinical tool confirming the diagnosis or monitoring disease activity of Wegener's granulomatosis (WG). Although several concepts concerning the pathophysiologic potentials of ANCA have been discussed, only sparse data about ANCA-endothelium interactions have been available. In this study, we have investigated the expression of PR-3 in cytokine-treated human endothelial cells using purified anti-PR-3 antibodies of patients with WG, murine and human monoclonal anti-PR-3 antibodies as probes. We were able to show that tumor necrosis factor-alpha, interleukin-1 alpha/beta, and interferon-gamma led to an increased PR-3 expression in the cytoplasm of endothelial cells by performing polymerase chain reaction analysis, Western blot, cyto-enzyme-linked immunosorbent assays, and confocal laser scanning microscopy. Moreover, PR-3 was also translocated into the cell membrane, becoming accessible to ANCA. Our data suggest a possible direct pathogenic effect of anti-PR-3 antibodies in WG and other vasculitides. Anti-PR-3 antibodies represent an important missing link in ANCA-endothelial interactions. PMID- 8353287 TI - Hodgkin's lymphoma-derived tissue serially transplanted into severe combined immunodeficient mice. AB - Hodgkin (H) and Reed-Sternberg (RS) cells are considered to be the malignant cell population in Hodgkin's disease (HD). To date, their analysis has been hampered by their scarcity in primary tumors, poor growth in vitro, and lack of an animal model. To establish an in vivo system for the characterization of the malignant cells in HD, tumor biopsy samples from 13 HD patients were transplanted beneath the renal capsule or into the liver of severe combined immunodeficient (SCID) mice. HD-derived tissue from three patients gave rise to human tumors in SCID mice. Three different histologic patterns were observed: (1) lymphoproliferative disease (LPD), (2) anaplastic large cell lymphoma (ALCL), (3) Hodgkin-like lesions (HDLL). Immunohistochemical analysis showed that the tumors consisted of activated B cells (CD30+, CD20+). Epstein-Barr virus (EBV)-encoded transcripts were found in 80% to 100% of the tumor cells, although H and RS cells in the primary tumors of two patients were EBV-. All tumors examined (3 of 3) and the majority (6 of 10) of cell lines recultured in vitro had an abnormal karyotype. Southern blot analysis of the human Ig heavy chain gene showed that monoclonal or oligoclonal tumors of different B-cell origin grew in the SCID mice from the same germ line-configurated primary biopsy specimen. Our data suggest that the human cells in the SCID mice have either been derived from EBV superinfected H and RS cells or from EBV-infected bystander cells. If the latter is true, then these bystander cells must be genetically abnormal. The genetic defect would be either aneuploidy or instable euploidy. In either case, the cells might proliferate into malignant aneuploid HDLL or ALCL under the influence of EBV and the special environment encountered in the SCID mice. PMID- 8353288 TI - Tyrosine phosphorylation of P160 BCR by P210 BCR-ABL. AB - It is well established that the chimeric BCR-ABL gene formed by joining parts of the BCR and ABL genes plays a key role in the pathogenesis of Philadelphia (Ph) chromosome-positive leukemias. We report that simultaneous expression of P210 BCR ABL and P160 BCR in simian COS-1 cells yielded stable complexes of these two proteins, and induced phosphorylation of P160 BCR on tyrosine residues in vivo. Tyrosine phosphorylation of a deletion mutant encoding 553 amino acids of BCR N terminal sequences was also detected when it was coexpressed with P210 BCR-ABL. We propose that tyrosine phosphorylation of P160 BCR by P210 BCR-ABL and their stable physical interaction may perturb normal BCR functions and that these alterations are directly involved in the pathologic processes found in Ph chromosome-associated leukemias. PMID- 8353289 TI - Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction. AB - The chromosomal translocation, t(8;21), is found frequently in acute myeloid leukemia (AML) with maturation (FAB-M2). We have previously mapped the translocation breakpoints of t(8;21) in a specific intron of the AML1 gene on chromosome 21. In this study, we cloned cDNAs synthesized from a cell line carrying t(8;21) by reverse transcription polymerase chain reaction (RT-PCR) using an AML1-specific primer. The analysis of the cDNAs structure has led to the identification of the fusion of AML1 with a gene named MTG8 on chromosome 8, which seems to be identical to ETO. Northern analysis using MTG8 (ETO) probes detected 7.8-kb and 6.2-kb RNAs and several minor RNAs in the cell line with t(8;21), but failed to detect any transcripts in a cell line without t(8;21). A set of primers were designed to detect the AML1/MTG8(ETO) fusion by PCR. The PCR amplified identical products in all 6 patients and one cell line with t(8;21), suggesting that the AML1/MTG8(ETO) fusion is a constant feature associated with t(8;21) and the junctions of the AML1/MTG8(ETO) fusion are restricted in a unique site. Because the PCR detection of the AML1/MTG8(ETO) fusion at the RNA level is highly sensitive, it can be used as a sensitive method for diagnosis and detection of minimal residual disease in t(8;21) leukemia. PMID- 8353290 TI - Evidence that red blood cell protein p55 may participate in the skeleton-membrane linkage that involves protein 4.1 and glycophorin C. AB - Human erythrocyte p55 is a peripheral membrane protein that contains three distinct domains in its primary structure: an N-terminal domain, an SH3 motif, and a C-terminal guanylate kinase domain. We used naturally mutated red blood cells (RBCs) with primary genetic defects resulting in the absence of protein 4.1 (4.1[-] hereditary elliptocytosis) or glycophorin C (Leach elliptocytosis). The absence of either protein was associated with the absence of p55. On a stoichiometric basis, the reduction in glycophorin C (about 80%) was concomitant to the lack of p55 in RBCs devoid of protein 4.1. Similarly, the reduction of protein 4.1 (about 20%) was equivalent to the absence of p55 in RBCs devoid of glycophorin C. These correlations suggest that p55 is associated, in precise proportions, with the protein 4.1-glycophorin-C complex, linking the skeleton and the membrane. The protein 4.1-glycophorin-C cross-bridge is known to be critically important for the stability and mechanical properties of human RBC plasma membrane. Because isoforms of protein 4.1, glycophorin C, and p55 exist in many tissues, these results provide evidence of a linkage between the skeleton and the membrane that may have implications in many nonerythroid cells. PMID- 8353291 TI - Orientation of erythrocytes in a strong static magnetic field. AB - The frequency of exposure to strong magnetic fields has increased as the magnetic resonance image-diagnostic technique (MRI) and passenger transport systems based on the principle of magnetic levitation have come into wider use. Accordingly, it has become necessary to more systematically assess their influence on the body and set strict guidelines on acceptable limits of magnetism exposure. Therefore, we have assessed the influence of an uniform static magnetic field (8 T in maximum) on normal erythrocytes. The erythrocytes were oriented with their disk plane parallel to the magnetic field direction. These erythrocytes were influenced even by 1 T and almost 100% of them were oriented when exposed to 4 T. Furthermore, the degree of orientation was not influenced by the state of hemoglobin (oxy: diamagnetic, deoxy and met: paramagnetic). The dependence of the measured degree of orientation on the intensity of the magnetic field was in good agreement with the theoretical equation for the magnetic orientation of diamagnetic substances. As a result of a numerical analysis based on the equation, the anisotropic diamagnetic susceptibility of erythrocytes was found to be delta chi = 8 x 10(-22) electromagnetic units/erythrocyte. It was almost in agreement with the calculated value delta chi = 6 x 10(-22) emu/erythrocyte estimated from the diamagnetism of the membrane constituents of erythrocyte. PMID- 8353292 TI - In vitro transcription from the human A gamma-globin gene promoter. AB - We report enhanced transcription from the human A gamma-globin gene promoter in nuclear extracts (NE) of erythroleukemia (K562) cells compared with that in HeLa NE. We do not observe differences in transcription levels in the two extracts with nonglobin promoter templates. Our findings, indicating preferential recognition of the globin gene promoter by nuclear factors in K562 cells, are consistent with results of studies previously reported by ourselves and others. A novel finding described here is that the addition of a double-stranded octamer motif oligonucleotide to K562 NE increases the level of transcription from the A gamma-globin gene promoter, suggesting a potential role for an octamer motif binding factor in the repression of A gamma-globin gene transcription. A cosmid construct containing extensive human gamma- and beta-globin gene promoter and structural sequences as well as upstream control sequences also exhibits higher levels of globin gene transcription in K562 NE than in HeLa NE. Our demonstration of the feasibility of efficient, globin promoter-specific in vitro transcription of this complex template offers a novel approach for the systematic analysis of the effects of putative regulatory factors on globin gene expression in vitro in the context of a genetic environment approximating that found in vivo. PMID- 8353293 TI - Effect on lymphocyte subsets of clotting factor therapy in human immunodeficiency virus-1-negative congenital clotting disorders. The Transfusion Safety Study Group. AB - Patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1) infection have lower CD4+ counts and CD4+/CD8+ ratios than controls. This is usually interpreted as a therapy-induced immunodeficiency. Our data re-examine the effect of therapy on peripheral blood mononuclear cell immunophenotypic subpopulations in all congenital clotting disorders. Since late 1985 we have prospectively observed HIV-1 uninfected persons with all types and severity of disorder. Controls were household members without clotting disorders or HIV-1 infection. Analyses of immunophenotype and treatment included a longitudinal random effects model. Compared with controls, age-adjusted CD4+ counts were significantly lower in treated patients (P < .0001) and in patients with all types of clotting disorders who were seldom or never treated (P = .0005). Significantly lower values among both treated and untreated clotting disorder subjects (P < .05) were likewise found for total lymphocytes, several other T cell subsets, and the CD4+/CD8+ ratio. For most indexes, including the CD4+ count and CD4+/CD8+ ratio, the type of clotting deficiency was not a significant variable. Comparing persons who had no or minimal therapy with those having the most showed increases in CD8+ (P = .0017) and CD20+ CD21- counts (P = .0255), and a lower CD20+ CD21+/CD20+ ratio (P = .0106) in the latter. Controls and persons with clotting disorders differ in CD4+ count. Among those with clotting factor disorders, there is no difference attributable to type of clotting disorder or factor therapy. Large amounts of treatment increased CD8+ and CD20+ CD21- counts, but were not associated with a change in CD4+ count. PMID- 8353294 TI - Disappearance of lysosomal storage in spleen and liver of mucopolysaccharidosis VII mice after transplantation of genetically modified bone marrow cells. AB - Mice homozygous for the gusmps allele lack beta-glucuronidase activity and provide a useful model for human Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome. Bone marrow (BM) transplantation was shown to correct the metabolic defect and to increase the life span of diseased animals. We have used this murine model in a preclinical study aimed at evaluating whether the techniques currently available for gene transfer into large mammalian and human BM cells will provide efficient enzyme replacement therapy in MPS patients. Autologous BM was transplanted into deficient mice after retrovirus-mediated transfer of the human beta-glucuronidase cDNA. Conditioning of recipients was performed by a single sublethal irradiation of 4.5 Gy, giving rise to low donor engraftment. In recipient mice analyzed until 145 days after gene transfer, the percentage of genetically modified hematopoietic cells was less than 5%. Nevertheless, beta-glucuronidase enzyme activity was detectable in various organs, including the brain, and disappearance of lysosomal storage was obvious in the liver and spleen. These results show that the autologous transplantation of genetically engineered BM cells could be beneficial in MPS patients. PMID- 8353295 TI - Functional iron deficiency. PMID- 8353296 TI - Platelet function and thromboxane synthesis in myeloproliferative disorders. PMID- 8353297 TI - Remission after erythropoietin administration for erythroleukemia--a case study. PMID- 8353298 TI - Piezoelectric extracorporeal shock wave lithotripsy in 93 patients with gallstones. AB - Ninety-three patients with gallstones were selected for extracorporeal shock wave lithotripsy (ESWL) with a piezoelectric device (EDAP LT-OI) to verify the efficacy and safety of this technique. Neuroleptoanalgesia with intravenous diazepam and phentanyl was performed in almost all patients. The treatment was combined with adjuvant litholytic therapy using oral ursodeoxycholic acid. Follow up period was nine months. Piezoelectric ESWL was able to disintegrate radiolucent gallstones in 97.9% of cases. By the ninth month 68 patients (73.1%) were stone-free. Best results were obtained with single stones smaller than 20 mm. After ESWL, surgical cholecystectomy was necessary in 2.1% of cases. This study confirms the efficacy and safety of piezoelectric extracorporeal shock wave lithotripsy combined with ursodeoxycholic acid adjuvant therapy for selected cases of gallstone disease. PMID- 8353299 TI - The impact of ultrasonography on the prognosis of pancreatic cancer. AB - The authors review 207 consecutive patients admitted for pancreatic cancer from 1960 to 1989 to the 1st Department of Surgery of the University of Rome "La Sapienza", in order to ascertain whether ultrasonography contributes to achieving the ideal goal of early diagnoses. The results achieved show a higher number of early diagnoses (< 1 month from first symptoms) performed by means of US, and a concurrent increase of cases amenable to radical surgery during the period 1975 1989, and basically from 1985 to 1989. Diagnostic imaging, namely US, is therefore deemed to provide earlier diagnoses and higher rates of pancreatic resectability. PMID- 8353300 TI - Combined granular cell tumour of the oesophagus and stomach: a case report and review of the literature. AB - The case of a 56-year-old man with contemporary benign granular cell tumour of the oesophagus and stomach is reported. Surgical resection of the oesophagus and stomach was performed after the diagnosis of squamous cell carcinoma on a superficial oesophageal biopsy which showed a pseudo-epitheliomatous hyperplasia of the stratified squamous epithelium covering the oesophageal Granular Cell Tumour (GCT). Hyperplasia was also found in the overlying gastric mucosa. Eight GCTs of the oesophagus, observed between 1980 and 1985, were reevaluated to compare the neoplastic characteristics and the occurrence of overlying epithelial hyperplasia. Only one patient was female; three had multiple oesophageal tumours and four showed pseudo-epitheliomatous hyperplasia. A review of the literature is included with emphasis on the rare cases of multiple GCTs. The association of chronic alcoholism with GCT of the gastro-intestinal tract is also stressed. PMID- 8353301 TI - Organ transplantation and branched chain amino acid metabolism in humans: methodological problems and possible pitfalls. PMID- 8353302 TI - Macronutrient oxidation in liver disease. PMID- 8353303 TI - Ultrastructural evidence for the axonal localization of caudodorsal cell hormone mRNA in the central nervous system of the mollusc Lymnaea stagnalis. AB - The technique of in situ hybridization has been used to evaluate the expression of an ovulation hormone mRNA (caudodorsal cell hormone; CDCH) in the central nervous system (CNS) of the mollusc Lymnaea stagnalis. Hybridization with radioactive as well as with nonradioactive labeled oligonucleotide and plasmid probes revealed a specific labeling on cell bodies of caudodorsal cells (CDCs), which are known to produce CDCH, on the light microscopical level. In addition, specific labeling was observed outside the cell bodies, as far as the cerebral commissure, where CDCH is released in the haemolymph. To investigate whether these signals represent an axonal localization of the CDCH mRNA, we performed in situ hybridization at the electron microscopical (EM) level. The results showed an intraaxonal localization of CDCH mRNA with digoxigenin labeled oligonucleotide and plasmid probes. Gold labeling was observed in secretion granules, and double labeling experiments showed that these granules also contain CDCH. This specific intragranular localization suggest that CDCH mRNA is transported through the axon and released by exocytosis in the haemolymph. PMID- 8353304 TI - mRNA structure, in situ, as assessed by microscopic techniques. AB - The secondary and tertiary structure of RNA, in situ, is thought to be involved in distinct functions such as directing association of the RNA with the cytoskeleton, enzymatic activity of some RNAs, and the control of translation. In situ transcription (IST), a procedure by which cDNA is synthesized in situ, has been used to assess mRNA structure in situ using fixed cells or tissues. Distinct banding patterns were noted for mouse and rat POMC. Unique IST banding patterns were observed when an oligonucleotide complementary to a putative POMC stem-loop structure was used to prime IST. Indeed local changes in banding patterns could be elicited by pharmacological agents which modulate POMC translation. Inhibition of POMC synthesis with NaF or dexamethasone decreased the number of POMC mRNAs in the polysome fractions and increased the intensity of high molecular weight IST derived bands. Forskolin, a stimulator of POMC synthesis, had the opposite effect. One mechanism by which translational control is thought to occur is by regulation of ribosome movement down the mRNA by specific binding of cytosolic proteins to RNA structure. Cytosolic protein fractions from AtT20 pituitary cells have been shown to specifically bind to the IST-predicted RNA structure. These findings suggest that 1) mRNA structure can be assessed in situ, 2) translation may be altered by the secondary and tertiary structure of mRNAs, and 3) a predicted stem-loop structure exists in situ in the 5'-end of POMC mRNA. PMID- 8353305 TI - Protocol of electron microscope in situ nucleic acid hybridization for the exclusive detection of double-stranded DNA sequences in cells containing large amounts of homologous single-stranded DNA and RNA sequences: application to adenovirus type 5 infected HeLa cells. AB - In order to gain a further insight into the relationships of the complex process of replication of adenovirus genomes to the substructures which occur in the nuclei of adenovirus type 5 (Ad5) infected HeLa cells, we have visualized directly, at the electron microscopic level, viral double-stranded DNA (dsDNA) in late infected nuclei by the use of a post-embedding in situ hybridization technique with a biotinylated specific DNA probe. The procedure is based on the removal of single-stranded (ss) nucleic acids by S1 nuclease. The highest levels of signal density for viral dsDNA were detected over the fibrils of the large, centrally located viral genome storage site and over the viral nucleoids of both clustered and isolated viruses. Lower but significant signals were observed over the fibrillo-granular network of the peripheral replicative zones, where both transcription and replication of viral DNA occur. On the other hand, the labeling of the enclosed viral ssDNA accumulation sites, also involved in viral replication but not transcription, was negligible, which suggests that, in the latter, the newly synthesized viral dsDNA immediately extends into the adjacent peripheral replicative zone to be transcribed and/or replicated. PMID- 8353306 TI - The use of in situ hybridization to study erythropoietin gene expression in murine kidney and liver. AB - In situ hybridization has been used to localize erythropoietin (EPO)-producing cells in murine kidney and liver. Peritubular interstitial cells were the only cell type that produced EPO in the kidney. The EPO-producing cells were primarily concentrated in the inner cortex but were also seen in the outer medulla and outer cortex. EPO-producing cells represented less than 10% of the total interstitial cell population. The number of EPO-producing cells per square centimeter of cortex directly correlated with the amount of renal EPO mRNA and varied in an inverse exponential manner with hematocrit. These results suggest that EPO is expressed in an all-or-none fashion in peritubular interstitial cells and that the oxygen carrying capacity of blood is the major regulator of renal EPO production. Peritubular interstitial cells were also identified as the renal source of human EPO in transgenic mice that expressed human EPO mRNA is a regulated fashion in the kidney. Transgenic mice exhibiting inducible supranormal liver expression of human EPO were used to identify EPO-producing cells in the liver. Hepatocytes surrounding central veins produced human EPO in these mice. Individual hepatocytes were able to modulate their production of human EPO depending upon the severity of anemia to which they were subjected. Two types of widely scattered cells produced EPO in severely anemic nontransgenic mice. Eighty percent of EPO-producing cells were hepatocytes and 20% were classified as being nonepithelial based on their nuclear morphology and location in venous sinusoids. PMID- 8353307 TI - Characterization of the suprachiasmatic nucleus in organotypic slice explant cultures. AB - Suprachiasmatic nuclei (SCN) from hypothalami of postnatal rats were maintained for 18-39 days in vitro as organotypic slice explants. Neuronal subtypes containing vasopressin (VP), vasoactive intestinal polypeptide (VIP), gastrin releasing hormone (GRP), and GABA were immunocytochemically identifiable in these cultures. In situ hybridization histochemistry was compatible with these SCN slice explant cultures, and mRNA encoding for VP was detected bilaterally within these nuclei. After 18 days in vitro, both VP mRNA and VP immunoreactivity increased from levels present on postnatal days 4 (the earliest age from which the explanted tissue was derived) to levels typical of adult SCNs. In contrast, the GRP expression remained low, characteristic of early postnatal animals and far lower than adult levels. This suggests that the developmental cues or programs necessary for enhanced VP expression are maintained in these cultures, while those affecting GRP expression are absent or inhibited. VIP-containing neurons were numerous in the cultures. Culture slices appeared healthy, and similar numbers and distributions of identifiable neurons within the SCN were observed, whether or not the slices were grown in the presence of serum. EM analysis revealed that the SCN in vitro is composed of tightly packed neurons, processes, and abundant synapses containing both clear and dense core vesicles, closely resembling the SCN in vivo. Vasopressinergic neuronal somata contained extensive Golgi systems and labeled secretory granules, the latter organelle being present also within processes and synaptic terminals. GABA-immunopositive processes and synaptic profiles were abundant, with labeling occurring particularly over secretory vesicles and mitochondria. This slice culture system effectively maintained much of the intrinsic organization and cellular components of the SCN for long periods in vitro and should be an excellent model system for studying the intrinsic molecular mechanisms and extrinsic cues which regulate neuronal phenotype in this circadian pacemaker. PMID- 8353308 TI - An assessment of the efficacy of in situ hybridization as a quantitative method by variance components estimation. AB - One serviceable feature of in situ hybridization is its potential for assessing relative levels of mRNA in specific regions of tissues and organs. To determine its efficacy as a quantitative technique, we applied a nested factorial design to a multifactorial experiment. Estimates of the magnitude of variance components then allowed an assessment of variation over samples of sections from the same tissue source, variation in label over 2 anatomical sites within the same section of tissue, as well as experiment-to-experiment variation. We found approximately 51% of the total variance arose from experiment-to-experiment variation, while approximately 21% of the total variance was due to variation in autoradiography grain density over neurons in the same brain region. Rat-to-rat variation accounted for approximately 11%. About 10% of the variance was due to variation between sections of tissue that were derived from the same tissue source and were hybridized in the same hybridization experiment. Variation between 2 homologous, bilaterally located brain regions located on the same tissue section (the right and left supraoptic nucleus), accounted for approximately 5% of the total variance. The remaining unaccounted error variance was approximately 2% of the total variance. Since an expected change in cellular content of a particular mRNA was observed as a function of experimental treatment, results suggest in situ hybridization is a useful quantitative method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353310 TI - In situ hybridization in HIV research. AB - In situ hybridization (ISH) for HIV is an arduous, demanding means of detecting viral genetic material in cells and tissues. Good ISH requires broad technical skills and devotion to controls for every step of the process as well as a critical eye when interpreting results. ISH may be used to detect HIV in three ways: by hybridizing to viral RNA, by hybridizing to proviral mRNA being produced for virion packaging, and by hybridizing to proviral DNA in the cytoplasm or integrated in the nucleus of an infected cell. Here we discuss the technical considerations involved and the problems encountered in using ISH to study the pathobiology of HIV infection. PMID- 8353309 TI - Differences of size and shape of active and inactive X-chromosome domains in human amniotic fluid cell nuclei. AB - It is a widely held belief that the inactive X-chromosome (Xi) in female cell nuclei is strongly condensed as compared to the largely decondensed active X chromosome (Xa). We have reconsidered this problem and painted X-chromosome domains in nuclei of subconfluent, female and male human amniotic fluid cell cultures (46,XX and 46,XY) by chromosomal in situ suppression (CISS) hybridization with biotinylated human X-chromosome specific library DNA. FITC conjugated avidin was used for probe detection and nuclei were counterstained with propidium iodide (PI). The shape of these nuclei resembling flat ellipsoids or elliptical cylinders makes them suitable for both two-dimensional (2D) and three-dimensional (3D) analyses. 2D analyses of Xi- and Xa-domains were performed in 34 female cell nuclei by outlining of the painted domains using a camera lucida. Identification of the sex chromatin body in DAPI-stained nuclei prior to CISS-hybridization was confirmed by its colocalization with one of the two painted X-domains. In 31 of the 34 nuclei the area AXi for the inactive X-domain was smaller than the area AXa for the active domain (mean ratio AXa/AXi = 1.9 +/- 0.8 SD, range 1.0-4.3). The signed rank test showed a highly significant (P < .0001) difference both between AXa and AXi and between the ratios r(Xa) and r(Xi), calculated by dividing the maximum length L of each X-domain by its maximum width W. In most nuclei (26/34) we found r(Xa) > r(Xi) demonstrating a generally more elongated structure of Xa. For 3D analysis a confocal scanning laser fluorescence microscope (CSLFM) was used. Ten to 20 light optical sections (PI-image, FITC-image) were registered with equal spacings (approx. 0.4 microns). A thresholding procedure was applied to determine the PI-labeled nuclear and FITC labeled X-domain areas in each section. Estimated slice volumes were used to compute total nuclear and X-domain volumes. In a series of 35 female nuclei most domains extended from the top to the bottom nuclear sections. The larger of the two X-chromosome domains comprised (3.7 +/- 1.7 S.D.)% of the nuclear volume. A mean ratio of 1.2 +/- 0.2 SD (range 1.1-2.3) was found for the volumes of the larger and the smaller X-domains in these female nuclei. In a series of 27 male amniotic fluid cell nuclei the relative X-chromosome domain volume comprised (4.0 +/- 2.6 S.D.)%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8353311 TI - Morphological modulation of intercalated cells in human fetal kidney. PMID- 8353312 TI - alpha-Thalassaemia. AB - The large number of naturally occurring mutants of this well-characterized locus provides an excellent opportunity for elucidating the relationship between its structure and function. Comparisons of what has been learned about the alpha globin locus with complementary observations on the beta-globin locus, provide a strategy for understanding the co-ordinate regulation of eukaryotic gene expression. From a practical point of view it is important to remember that millions of individuals throughout the world are carriers of alpha-thalassaemia and every year many thousands of pregnancies are at risk of producing children with the severe alpha-thalassaemia syndromes. The data summarized here provide the basis for accurately predicting the genotype in such cases and thus enabling appropriate prenatal testing. However, because this is a genetic disease that predominantly affects individuals from countries with limited health resources, simpler and cheaper methods of screening and diagnosis will have to be developed before this information has a significant impact on the attendant morbidity and mortality (see Chapter 9, this volume). PMID- 8353313 TI - beta-Thalassaemia. PMID- 8353314 TI - The population genetics of the haemoglobinopathies. AB - The haemoglobinopathies are the commonest single gene disorders known, and are so common in some regions of the world that the majority of the population carries at least one genetic abnormality affecting the structure or synthesis of the haemoglobin molecule. The prevalence of the common haemoglobinopathies (the alpha and beta-thalassaemias, HbS, HbC and HbE) is almost certainly a result of the protection they provide against malaria, as the epidemiological evidence reviewed in this chapter shows. World-wide, the distributions of malaria and the common haemoglobinopathies largely overlap, and micro-epidemiological surveys have confirmed the close relationship between the disorders. However, there are complications to this picture which appear to undermine the malaria hypothesis. First, in some areas, malaria and haemoglobinopathies are not coincident. Second, the malaria hypothesis does not easily explain why no two regions of the world have the same haemoglobinopathy or combination of haemoglobinopathies. The majority of mutations have arisen only once and are regionally specific. By using molecular characterization of mutations and the analysis of haplotypes on haemoglobinopathy-bearing chromosomes it is possible to show how a combination of selection by malaria, genetic drift and population movements can explain the first complication. In order to explain the second, we have argued that malaria selection has operated relatively recently on human populations (within the last 5000 years). The present distribution is then seen as the result of selection elevating sporadic mutations in local populations. In the absence of sufficient gene flow to spread all mutations to all populations, the consequence is a patchwork distribution of haemoglobinopathies. Given time, we would expect the mutations that protect and do not compromise the health of their carriers to become widely disseminated, but it is likely that human intervention will alter this process of natural selection. PMID- 8353315 TI - Management of Cooley's anaemia. AB - The current management of Cooley's anaemia has succeeded in prolonging the patient's life to at least the fourth decade, in allowing a number of the patients to procreate children, and in allowing most of them to lead a nearly unrestricted normal life. The price to be paid for this is the cumbersome and expensive adherence to a rigorous regimen of chronic transfusion and compliance with chelation therapy. Economical and psychological factors make it difficult for many patients to benefit from these advances, but those who can may be reasonably assured of a long and fruitful existence. It must be realized that the only defect in Cooley's anaemia is one of haemoglobin synthesis, and well-managed patients are in any other aspect capable of leading a normal life. In certain areas of the world, such as Cyprus (Loukopoulos et al, 1990) and Sardinia (Cao et al, 1990), extensive and intensive programmes of prenatal screening have reduced to nearly negligible levels the birth of children with Cooley's anaemia (see Chapter 9 this volume). Yet, in many countries a complete management of Cooley's anaemia is today not feasible for economic or cultural reasons, and this disease remains a serious public health problem. The future of the management of Cooley's anaemia appears at the moment full of hopes and frustrations (Gale, 1989; Bank, 1990). However, it is important to understand that if the current group of patients with Cooley's anaemia have to be the beneficiaries of future developments (be it genetic engineering and/or advances in histocompatibility matching), it is necessary that these patients be maintained in excellent clinical shape. It would be very sad when a cure for Cooley's anaemia became available, if most patients could not avail themselves of it because of pre existing irreversible body damage. PMID- 8353316 TI - Bone marrow transplant for the haemoglobinopathies: past, present and future. AB - Bone marrow transplantation (BMT) is the only treatment currently available which can cure thalassaemia and sickle cell anaemia. However, it is not without risk and the complications of graft failure, GVHD, veno-occlusive disease, interstitial pneumonitis and infections, together with the toxicity of the conditioning therapy result in a transplant-related mortality in children of 10 20%. For the survivors, long-term sequelae include chronic GVHD, endocrinopathies and an increased incidence of secondary malignancies. The decision to offer BMT to a patient with a haemoglobinopathy must be based on a knowledge of the relative risks of transplant and conventional therapy. However, in sickle cell anaemia, a subset of patients with particularly severe disease can be identified at an early age when the risks associated with BMT are at their lowest. In thalassaemia, chelation therapy can delay the onset of organ damage due to hypertransfusion but is unlikely to prevent it entirely. The results of BMT in children without organ impairment are excellent and BMT must now be considered a real alternative to conventional treatment. Gene therapy is an exciting prospect for the future but recent progress in retroviral gene transfer has been hindered by poor infection efficiencies and expression levels in the target cells. The identification of the positive regulatory elements of both the alpha- and beta globin genes may resolve some of these problems. Finally, alternative gene delivery systems are being investigated, but the introduction of gene therapy for the haemoglobinopathies into clinical practice may need to await successful gene targeting and replacement. PMID- 8353317 TI - The regulation of human globin gene expression. AB - The haemopoietic system provides a well-characterized and accessible system for studying the mechanisms of developmental regulation and differentiation in higher eukaryotes. Our current understanding of the steps involved in the early stages of differentiation are poorly understood but a great deal is now known about the mechanisms by which globin expression is regulated in cells committed to the erythroid lineage. Many of the critical cis-acting sequences and some of the important trans-acting factors involved have been identified and current work is focusing on how these interact to produce high levels of tissue-specific and developmentally regulated expression of the human globin genes. PMID- 8353318 TI - Sickle cell disease pathophysiology. AB - The primary pathophysiological event in the erythrocytes of individuals with the various sickle syndromes is the intracellular aggregation or polymerization of sickle haemoglobin (HbS). The extent of polymerization is determined by the intracellular haemoglobin composition (% HbS and % HbS A, A2 and F), concentration (MCHC and % of dense cells) and oxygen saturation, as well as minor factors such as intracellular pH and DPG concentration. Intracellular HbS polymerization leads to a marked decrease in the flexibility or rheological properties of the sickle erythrocytes and obstruction in various microcirculatory beds, as well as chronic anaemia. Other abnormalities in the properties of the sickle erythrocytes, including membrane abnormalities, changes in ion fluxes and volume and endothelial adhesion, result from acute and chronic oxygen-linked polymerization events and may, in turn, modify polymerization. However, within a good approximation, many aspects of sickle cell disease pathophysiology--for example variations in anaemia among the different sickle syndromes--can be explained in terms of differences in polymerization tendency. Thus, the effects of alpha-thalassaemia can be explained with reference to changes in MCHC and syndromes with high HbF are understandable in terms of the sparing effect of HbF on polymerization. Recent therapeutic approaches to sickle cell disease focus on attempts to reduce intracellular HbS polymerization by altering the haemoglobin molecules, erythrocyte properties, or the distribution of intracellular haemoglobin species. The last, through pharmacological elevation of HbF, has become the central focus of much laboratory and clinical research in recent years. Agents such as hydroxyurea (with or without recombinant erythropoietin) and butyrate compounds elevate HbF (and reduce HbS) in a majority of sickle erythrocytes, thus decreasing intracellular polymerization. Current prospective protocols are designed to see if these changes cause clinical improvement at acceptable doses. Other treatment strategies, including bone marrow transplantation and possible gene replacement therapies, are also under active clinical or laboratory investigation. PMID- 8353319 TI - The clinical features of sickle cell disease. AB - Evidence from structural studies of DNA suggest that the sickle cell mutation has arisen on at least three separate occasions in Africa and as a fourth independent mutation in the Eastern Province of Saudi Arabia or India. The pathophysiology of sickle cell disease is essentially similar in these different areas although the frequency and severity of complications may vary between areas. Generally, the chronic haemolysis and resulting anaemia is well tolerated, although serious morbidity and occasionally mortality may be associated with the aplastic crisis or cholelithiasis. Exacerbation of anaemia below steady state levels occurs with chronic glomerular damage and renal failure, especially in older patients. Most of the morbidity of the disease arises from bone marrow necrosis in the painful crisis or from vaso-occlusive manifestations. Changes in the splenic circulation result in life-threatening episodes of acute splenic sequestration, the chronic morbidity of hypersplenism, and splenic dysfunction renders children prone to pneumococcal septicaemia. Chronic organ damage contributes to chronic leg ulceration in adolescence and progressive renal, pulmonary, and occasionally cardiovascular impairment in later life. The clinical spectrum of homozygous sickle cell disease varies widely between patients. Factors contributing to this variability include alpha-thalassaemia, persistence of high HbF levels, haematology, social circumstances, and geographical and climatic variation. Many of the causes of mortality may be prevented or more effectively treated, leading to increased survival and an increased quality of life in affected subjects. PMID- 8353320 TI - Dynamics of the bacterial genome: deletions and integrations as mechanisms of bacterial virulence modulation. AB - Bacterial virulence is a multifactorial phenomenon, arising from the coordinate action of special abilities of the infectious agents, termed as virulence factors, which is crucial for the infectious process. The genetic determinants encoding those factors are termed virulence associated genes, which can be located on the bacterial chromosome or on extrachromosomal elements (plasmids). Various examples have repeatedly demonstrated that bacterial genome dynamics contributes to virulence modulation. Strikingly, a reduced in vivo virulence of the pathogens was shown to be due to the spontaneous loss of virulence associated genes. The deletion events can involve chromosomal as well as plasmid regions. Also integration of plasmids into the chromosome are considered as dynamic events. The new genetic location of the formerly plasmid encoded virulence associated genes can result in an alteration of virulence expression. PMID- 8353321 TI - Chromosomal rearrangement and serovar conversion in Leptospira biflexa strains. AB - A bacterial population change involving chromosomal rearrangement and phenotypic changes in antigens, proteins and lipopolysaccharides is described for strains of Leptospira biflexa that were previously grown in media containing homologous oligoclonal antibodies. The chromosomal rearrangement phenomenon showed that the variants differed from the parent strains, yet they were similar to phenotypically related serovars already occurring in nature. Accordingly, in vitro serovar conversion mediated by chromosomal rearrangement, due to as yet unknown genetic mechanisms, had occurred. PMID- 8353322 TI - Pseudomonas fluorescens var. aluphilia--the influence of Al3+ on the growth rate and formation of phenazines. AB - The thin-layer chromatographic characterization of phenazine derivatives formed by a subspecies of Pseudomonas fluorescens under iron deficiency conditions in the presence of Al3+ showed that regarding type and quantity they were relatively different from phenazines generated on the basis of Be(2+)-containing culture media or containing neither Be2+ ions nor Al3+ ions. A comparison has shown that bacterial synthesis of phenazine derivatives is stimulated more by Be2+ ions than by Al3+ ions. PMID- 8353323 TI - Optimal selection of biochemical tests to identify microbial species. AB - Microbial species are mainly identified by biochemical tests. A numerical procedure is described, serving as an aid to decide which biochemical tests should be used and to check if these tests are sufficient to discriminate the species under consideration. PMID- 8353324 TI - Effect of growth of Bacteroides fragilis at different redox levels on potential pathogenicity in a HeLa cell system: demonstration by confocal laser scanning microscopy. AB - During trauma, the intestinal anaerobe, Bacteroides fragilis, may enter into a pathogenic state. The process coincides with changing environmental conditions particularly the redox level in situ. To gain insight into this phenomenon B. fragilis was grown at different redox levels, and the invasive potential was examined using an in vitro model consisting of HeLa cell monolayers. The clinical strain AIP 5-86 was taken from a small collection of B. fragilis strains able to penetrate into tissue cell monolayers when selected by an acridine orange-crystal violet fluorescent staining technique. Following preliminary investigation by confocal laser scanning microscopy (CLSM), this particular strain was regarded as representative for examining the invasive potential. After growth in a defined medium under oxidizing, reducing or intermediate Eh7 conditions, the washed mid log phase bacteria were allowed to interact with HeLa cell monolayers for 45 min at 37 degrees C. The results were extensively monitored by CLSM to follow the reactions in a stereoscopic dimension. In addition, the bacteria were examined by transmission and scanning electron microscopy before interaction to distinguish characteristics in surface configuration. The growth of the bacteria at particular redox levels seemed to influence their potential for pathogenicity. After growth at relatively high Eh, the bacteria easily penetrated into the HeLa cells, but not at low Eh, as determined by the laser scanning studies. Examination of the bacteria alone by transmission and scanning electron microscopy revealed small vesicles and a tendency to aggregate after growth at the low redox level while there were rather few vesicles and an implied dispersion at the high redox level. This leaves it open whether the invasiveness was based on the alterations found during growth of the bacteria. Different redox levels as well as the respective changes of the bacterial surface may help to discern the commensal from the pathogenic state of B. fragilis. PMID- 8353325 TI - Characterization of the murine macrophage receptor for group B streptococci. AB - The macrophage has been shown to bind potentially pathogenic bacteria in the absence of serum components or opsonins but the mechanism is poorly understood. The rich array of sugars on the surface of group B streptococci plus the presence of membrane-associated lectin receptors on the macrophage suggests that this is a likely means for bacterial recognition by these host defense cells. Inhibition studies with free sugars and neoglycoconjugates of bovine serum albumin, however, failed to confirm this hypothesis. Furthermore, neuraminidase-treatment to expose galactose residues and the use of isogenic bacterial strains having no capsule or no capsular sialic acid yielded no confirmation of lectin-mediated recognition. The trypsin-sensitive receptor exhibited temperature dependence and a requirement for divalent cations distinct from that reported for the lectin-like galactose receptor. The activity of this streptococcal binding receptor was inhibited by 2 deoxy-D-glucose but not by neutrophil elastase. Pre-exposure of macrophages to bound fibronectin and treatment with phorbol ester each enhanced bacterial binding. These data fail to support a role for the galactose lectin and provide preliminary evidence for involvement of the leukocyte integrins in macrophage recognition of group B streptococci. PMID- 8353326 TI - Fungal pathogens in etiology of septic shock in neutropenic patients with cancer (short communication). AB - During the 3 years from 1989 to 1991, we evaluated the etiology of septic shock cases and infection-associated mortality. A total number of 38 patients was included in the study, according to the criteria for septic shock (SS), (Intensive Care Medicine Society, 1989). In 1989, P. aeruginosa and Enterobacteriaceae among the pathogens prevailed. In 1990 and 1991, S. aureus, enterococci and fungi were most frequent. From 8 patients with SS in 1990, the shock was due to Candida albicans in 1 and to mucoraceae in 3 patients. In 10 patients examined in 1991, 8 cases of SS were due to Candida albicans, Aspergillus niger, Fusarium solani and Acremonium strictum. The decrease of the incidence of shocks and increase of fungal etiology were found to be associated with the use of quinolones in prophylaxis and cephalosporines, aminoglycosides and vancomycine in empiric therapy in febrile neutropenic patients. PMID- 8353327 TI - Critical examination of an enzyme immunoassay for detection of positive IgM antibodies against toxoplasma in newborns. AB - The Toxonostika IgM test, which has been examined in this study, is a modified antibody capture test (7). Evaluation with sera from newborns revealed that, like in the ELISA tested in 1988, doubtful or false positive results were obtained in 10% of the cases (6). Therefore, a positive toxoplasmosis IgM result in newborn sera should always be retested with another test system. PMID- 8353328 TI - Intranuclear development of asexual and sexual generations of Eimeria hermani Farr, 1953, the coccidian parasite of geese. AB - Both merogonic and gamogonic stages of Eimeria hermani occurred within the nucleus of epithelial cells of the intestine of experimentally infected goslings (Anser anser domesticus L.). They were located within a parasitophorous vacuole. Several developing meronts were often observed in one host nucleus and each of them had its own parasitophorous vacuole. We suppose that two generations of meronts were formed by ectomerogony from 2 to 4 days post infection (DPI). During the gamogony (4-6 DPI), we observed invagination of the host cell nucleoplasm into the parasites and we suppose that this may be connected with the process of the parasite's feeding. PMID- 8353329 TI - First clinical use of the Possis synthetic coronary graft. AB - The Possis polytetrafluoroethylene Permaflow coronary graft incorporates a Venturi resistor within the graft. Insertion is constructed by creating an anastomosis to the superior vena cava with subsequent anastomoses in sequence to coronary arteries requiring grafting. Finally, the graft is sewn to the aorta. The Venturi resistor controls flow through the aortocaval fistula, maintaining systemic pressure proximal, permitting systolic and diastolic flow to the grafted coronary arteries while maintaining constant flow through the graft. Animal studies demonstrated long-term patency. This graft was implanted in a patient with unstable angina pectoris and inadequate native conduit. Catheterization 6 weeks postoperative revealed patency of all anastomoses. PMID- 8353330 TI - Present status of reconstructive surgery for aortic valve disease. AB - Most surgical techniques for reconstruction of the aortic valve, although described a long time ago, are now feasible with satisfactory results. The general surgical principles for successful reconstruction, and the operative techniques of annuloplasty, commissurotomy, free edge resuspension, unrolling and thinning, and cusp extension are described. Methods for intraoperative evaluation of the repaired valve are also described. Between August 1988 and April 1992, 166 patients underwent aortic valve reconstruction with a 3.2% hospital and 1.2% late mortality. There were no thromboembolic events in the patients with isolated aortic valve repair. The reoperation rate was 6.5%. Echocardiographic study at last follow-up showed stable results at 4 years maximum follow-up. PMID- 8353331 TI - Application of fresh and cryopreserved homografts harvested from transplant patients for correction of complex congenital heart disease. AB - In recent years, the use of homograft tissue in cardiac surgery has increased so that supply is limited. Since October 1990, aortic and/or pulmonary valves were collected from 17 transplant recipients at the Department of Cardiovascular Surgery of the University of Padova Medical School (11 male, 6 female, mean age 43.4 years, range 11 months to 61 years). The indications for transplant were dilated cardiomyopathy in 7, and end-stage ischemic heart disease in the remaining 10 patients. Twelve such valves have been subsequently reimplanted either as fresh or as cryopreserved valved homografts in the repair of different forms of congenital heart disease, by means of different tailoring techniques (7 male, 5 female; mean age 4.8 years [range 1 day to 18 years]; transposition of the great arteries = 5 cases; tetralogy of Fallot = 3 cases; hypoplastic left heart syndrome = 2 cases; double outlet right ventricle = 1 case; truncus arteriosus = 1 case). Overall, early mortality was 25%. None of these deaths could be related to the use of homografts. There have been no instances of valve related complications among nine patients surviving surgery at a mean follow-up of 11 months. All patients having heart explanted should be regarded as potential sources for aortic and pulmonary homografts. PMID- 8353332 TI - Aortic valve replacement using a continuous suture technique. AB - The continuous suture technique has been proposed as an alternate method for aortic valve replacement (AVR). Advantages include a decreased ischemic and bypass time. Despite reports of a low incidence of perivalvular leak, wide use of the continuous suture technique has not been adopted. This report reviews our experience with the continuous suture technique. From January 1984 through November 1991, 181 consecutive patients underwent AVR using the continuous suture technique. The mean age was 61 years (range 6 to 88 years). Diagnoses included pure aortic stenosis (AS) in 41%, aortic insufficiency (AI) in 31%, and a combination of AS and AI in 28%. Fifty-six patients underwent isolated AVR and 125 underwent AVR combined with other procedures. The overall early mortality was 5.5%. Early mortality for isolated AVR was 0% (0/56) and was 8.0% (10/125) for those undergoing concomitant procedures. Late mortality was 4.7% in a mean follow up of 30 months (range 1 to 86 months). The incidence of perivalvular leak was 2.3% (4/171 operative survivors). Perivalvular leak was mild in two, and moderate in two; none required reoperation. Perivalvular leak developed only in patients whose suture line was not reinforced with glutaraldehyde treated pericardium. The continuous suture technique is a quick and effective method for AVR and results in a low incidence of perivalvular leak. PMID- 8353333 TI - Implantation of the unstented bioprosthetic aortic root: an improved method. AB - The problem of early onset aortic insufficiency as seen with the scalloped, subcoronary homograft aortic valve replacement is reduced with the use of a total root replacement. In addition, the naturally competent aortic root is more durable. From September 1985 to April 1991, 26 consecutive patients underwent aortic root replacement with 10 autografts, 14 homografts, and 2 xenografts using a modified implantation method. Twenty-five patients were discharged from the hospital. This partial inclusion root technique for implanting unstented valves in the aortic position decreases the probability of early failure secondary to technical malalignment at the time of implantation. In contrast to total root replacement, it avoids the need to destroy the recipient aortic root. A longitudinal aortotomy is performed to the aortic annulus in the mid-portion of the noncoronary sinus. The proximal suture line is interrupted with the valve oriented in the anatomical position. Circumferential running monofilament side-to side anastomoses approximate the donor coronary ostia to the recipient. A running medial and lateral posterior suture line to the lateral superior portions of the aortotomy completes the integrity of the anterior wall of the implantation. One autograft attempt failed and one homograft patient died postoperatively. Follow up ranges from 1 to 6 years in 24 patients. Postoperative aortic insufficiency was significant in one case due to inappropriate sizing of the proximal aortic suture line. There has been no evidence of progressive aortic insufficiency detected by the early onset of diastolic murmurs or echocardiograms as was our previous experience with the scalloped subcoronary method. PMID- 8353334 TI - Mitral and aortic annular enlargement for insertion of adequate size prosthetic valves. AB - Mitral and aortic valve rings were radically enlarged in a 70-year-old white female presenting with unusually tiny and severely stenotic rheumatic mitral and aortic valve disease. A common aorto-left atrial incision created by cutting across the two valves made it possible to implant adequate size St. Jude valves. The resulting defect in the roof of the left atrium and the aortic root were closed with a generous patch of polytetrafluoroethylene (PTFE). The center of the patch and the unattached segments of the two prostheses were incorporated with interrupted horizontal mattress sutures. PMID- 8353335 TI - A modified reconstruction technique after extended anterior descending artery endarterectomy. AB - An increasing number of patients with advanced coronary artery disease and diffusely complex atherosclerotic lesions are referred for coronary artery bypass surgery (CABG). Under these circumstances, complete myocardial revascularization with an adequate distal runoff can only be achieved by extensive manual endarterectomy and a reconstructive procedure prior to conduit placement. Because of the numerous septal and diagonal branches of the left anterior descending artery (LAD), an extended and meticulous endarterectomy is warranted. Placement of the internal mammary artery (IMA) on such a widely opened vessel requires reconstruction with a vein patch and the IMA. A modified technique of extended manual endarterectomy, distal vein patch, and proximal IMA reconstruction and revascularization is described. This technique was used in six patients between October 1990 and December 1992 with 100% early survival. This technique is less time consuming and more importantly allows for a direct artery-to-artery anastomosis with the potential for a better long-term patency. PMID- 8353336 TI - Intraoperative coronary angioscopy--technique and results: a study of 38 patients. AB - Over a period of 11 months, 38 patients submitted to coronary artery revascularization underwent intraoperative angioscopy of the coronary arteries and internal thoracic arteries. Fifty-nine lesions were observed, but only 31 stenoses responsible for coronary insufficiency were observed (33%). Forty-four distal anastomoses were explored (47%) but ten of these explorations were incomplete. None revealed technical failure of the anastomosis. Thirteen harvested left internal mammary arteries were explored. One of the explorations led to rejection of the graft due to an intimal fracture. Some tiny intimal flaps were observed in our experience, as in others. Although the iatrogenic origin of these lesions in relation to the introduction of the angioscope is obvious, it does not seem to influence the outcome of the operation. In our opinion, two main fields appear to be developing in coronary angioscopy: preoperative assessment of the quality of internal thoracic artery grafts, and control of distal graft anastomoses. The flexibility of the angioscopes and of the leading catheters must be improved to minimize the risk of arterial wall traumatic lesions. PMID- 8353337 TI - Use of a Dacron mesh coated pericardium for aortic augmentation. AB - A technique is described for aortic augmentation with Dacron mesh coated pericardial patch. This method avoids the use of synthetic graft material with the potential for weak adherence of pseudointima and microembolization. Hemostasis is improved and fibrous tissue ingrowth into the mesh prevents late aneurysm formation. The incorporation of the pericardial patch into the aortic wall and the normal endothelialization of the patch is documented after a 5-year follow-up. PMID- 8353338 TI - Future cardioprotective considerations. AB - Remarkable strides have been made in perioperative myocardial protection for heart operations. Recent advances in understanding the physiology of myocardial ischemia and its protective responses suggest that there is a possibility for further improvement. Some of these strategies are discussed in this article, which updates current thinking in regard to operative developments contributing to myocardial protection, preconditioning, inhibition of adenosine triphosphate catabolism, the critical role of adenosine, management of myocardial edema, antioxidant therapy, endothelial cell injury, and the interaction between activated leukocytes and the endothelium. Some potential new directions for cardioprotection are identified. PMID- 8353340 TI - Modified elephant trunk procedure. PMID- 8353339 TI - Current management of the Wolff-Parkinson-White syndrome. AB - In this review, we discuss the pathophysiology of the Wolff-Parkinson-White (WPW) syndrome and describe medical, surgical, and catheter based principles. WPW syndrome results from the congenital presence of impulse-conducting fascicles, known as accessory pathways (APs) or bypass tracts, which connect atria and ventricles across the annulus fibrosis and are capable of preexciting portions of the ventricular myocardium. Once triggered, atrioventricular reciprocating tachycardias (AVRTs) generally result from depolarization wavefronts moving anterograde through the AV node to the ventricles and returning retrograde to the atria along the AP. Rapid AVRT decreases ventricular filling time and cardiac output, resulting in symptoms. Medications that prolong AP refractory periods (flecainide, propafenone, and amiodarone) prevent rapid AP anterograde conduction (from atria to ventricles) in atrial tachycardias such as atrial fibrillation or flutter. In emergencies, adenosine can be used to terminate the AVRT of WPW syndrome. Otherwise, Class IA or IC antiarrhythmic agents are used to slow AP conduction either with or without AV nodal blocking agents. Open chest surgical ablation of a bypass tract in a symptomatic patient was first reported in 1968. The original endocardial surgical techniques for localizing and dividing APs were refined and an alternative epicardial approach has been developed. Reported mortality rates in experienced hands were 0% to 1.5% in large series for patients without additional cardiac abnormalities. Catheter delivered radiofrequency (RF) energy is now applied intravascularly to ablate APs. Since the first large series of patients undergoing RF ablation was reported in 1989, the procedure had proved safe, cost effective, and well tolerated. RF ablation has become the initial nonpharmacological treatment of choice for WPW syndrome; surgical ablation has become relegated to those cases where symptoms are intolerable and RF ablation is not feasible. PMID- 8353341 TI - Percutaneous femoropopliteal graft placement. AB - PURPOSE: Femoropopliteal bypass surgery is now recommended for the treatment of long-segment or diffuse superficial femoral artery disease. The authors describe a technique for percutaneous placement of a prosthetic femoropopliteal graft. PATIENTS AND METHODS: The technique has been accomplished with conventional polytetrafluoroethylene graft material and a variety of implantation techniques in eight patients. RESULTS: Technical success was achieved in all patients who underwent graft placement. Grafts up to 28 cm in length were placed, and graft patency was demonstrated up to 10 months after implantation. Six of the eight patients were asymptomatic during the follow-up period; one patient who had symptoms during this time underwent thrombolysis and redilation of the distal stent, and the symptoms resolved. In the other patient with symptoms, the procedure failed clinically because of poor runoff. CONCLUSION: This study demonstrates the feasibility of percutaneous graft placement in the femoral artery, but durability must be established in relation to traditional bypass surgery before it can be recommended on a wider scale. PMID- 8353342 TI - Percutaneous peripheral atherectomy. PMID- 8353343 TI - Transcatheter therapy of severe acute lower extremity ischemia. AB - PURPOSE: Transcatheter methods of revascularization were performed in 11 patients with severe acute lower extremity ischemia and extensive vascular occlusions in whom surgical revascularization was not possible (10 patients) or was not preferred (one patient). PATIENTS AND METHODS: The acute ischemia was considered category 2 in nine patients and category 3 in two. Vascular occlusions were located in the superficial femoral artery in four patients, popliteal artery in 10, all three crural arteries in 10, and two crural arteries in one. Transcatheter methods included accelerated thrombolysis with 325,000 to 1.75 million U of urokinase, adjunct angioplasty, use of intraarterial vasodilators, and creation of pedal arterial flow loops. RESULTS: Initial success was 100% in the nine patients with category 2 ischemia. Eight limbs were saved; one occlusion at 10 days necessitated below-knee amputation. For the two patients with category 3 ischemia, one procedure failed and the other reduced the level of amputation. CONCLUSION: In patients with severe acute ischemia, transcatheter revascularization is a viable treatment option when strategies for reperfusion establish both inflow and microcirculatory outflow. PMID- 8353344 TI - Emergent renal artery revascularization for acute anuria. PMID- 8353345 TI - Extensive aortic and renal artery dissection following percutaneous transluminal angioplasty. PMID- 8353346 TI - Endovascular grafting in elastase-induced experimental aortic aneurysms in dogs: feasibility and preliminary results. AB - PURPOSE: A new model of aortic aneurysm was developed in 12 beagles to study the feasibility of endoluminal exclusion of aortic aneurysms. MATERIALS AND METHODS: After preliminary experiments in four dogs, aneurysms were induced by infusing elastase into an isolated segment of the abdominal aorta in eight dogs. To create aortic endoprostheses, a Palmaz stent was sutured onto each end of an ultrathin Dacron tube. Endoprosthesis placement was performed under fluoroscopic and intravascular ultrasonographic (US) guidance. The endoprostheses were introduced via a femoral arteriotomy, through a 12-F sheath positioned in the aorta, and then were expanded on an angioplasty catheter. RESULTS: Intravascular US and aortography showed aneurysms in the elastase-perfused area in the eight animals and demonstrated the exclusion of the aneurysm by the endoprostheses in six cases. Intravascular US was more accurate than aortography in demonstrating two cases of endoprosthesis dysfunction. Aneurysm formation was proportional to the loss of elastic tissue observed at histologic examination of the elastase-infused area. Macro- and microscopic examinations confirmed thrombosis of the excluded part of the aneurysm and patency of all grafts. CONCLUSION: This model and intravascular US appear helpful in exploring the feasibility of endovascular treatment of abdominal aortic aneurysm. PMID- 8353347 TI - Effectiveness of a prolapsed bird's nest filter. AB - PURPOSE: The authors evaluated the variable deployment of the Bird's Nest filter, including frequency and extent of prolapse in clinical use, and analyzed the effects of this variability on clot-trapping efficiency with an in vitro model. MATERIALS AND METHODS: In the clinical placement of 20 filters, the average length of cephalic filter wires from the center of the filter was measured from radiographs obtained immediately after placement. To analyze the effects of prolapse, a variable-rate pump was used to mimic the effects of respiration on IVC flow. Four clot sizes (5 x 20, 5 x 40, 10 x 20, and 10 x 40 mm) were evaluated with four filter configurations with wires stretched to different lengths in a cephalic direction from the center of the filter: 2 cm (normal tight), 5 cm (normal-loose), 8 cm (moderate prolapse), and to a maximum of 12 cm (maximum prolapse). Ten passes for each clot size were performed with each filter configuration in both the horizontal and vertical positions. The smallest clots were also tested with a slower constant-rate pump. RESULTS: In clinical use, the average length of the filter wire was 5.4 cm (range, 1.2-9.0 cm). With the variable flow pump, the in vitro degree of prolapse did not significantly decrease the trapping efficiency for any but the smallest (5 x 20-mm) clots, for the maximum prolapse configuration in the horizontal position (P = .01). In addition, for these clot sizes, the filter was more efficient with the slower constant rate compared with the faster variable rate; this difference was only statistically significant in the horizontal position for the maximum prolapse configuration (P = .007). CONCLUSION: The results suggest that in clinical practice, a prolapsed Bird's Nest Filter remains effective for all but small clots. PMID- 8353348 TI - Acute clot-trapping efficiency in dogs with compacted versus elongated wires in bird's nest filters. AB - PURPOSE: The clot-trapping efficiency of the Bird's Nest filter was studied in dogs with the stainless steel wires in a compacted versus fully elongated configuration. MATERIALS AND METHODS: Bird's Nest filters were placed infrarenally with the wires compacted in 10 dogs and with the wires elongated in an additional 10 dogs. The dogs were separated into two groups, five dogs with each wire configuration in each group. In group 1, 10 unlabeled 6 x 30-mm blood clots were injected into the inferior vena cava. In group 2, six 6 x 10-mm, four 6 x 15-mm, and four 6 x 30-mm labeled clots were introduced. RESULTS: In group 1, clot-trapping efficiencies were 82% for the compacted versus 86% for the elongated configuration, as seen on serial cavograms and pulmonary angiograms. In group 2, clot-trapping efficiencies were 90% for the compacted versus 97% for the elongated configuration, as seen at fluoroscopy. Clot size did not affect trapping efficiency. CONCLUSION: Acute clot-trapping efficiency of Bird's Nest filters did not differ when the wires were in a compacted versus elongated configuration. This study suggests that placement of a Bird's Nest filter in the elongated configuration may be satisfactory and may not indicate placement of a second filter. PMID- 8353349 TI - 1993 SCVIR annual meeting notes. PMID- 8353350 TI - Closure of a duodenal fistula with fibrin sealant. PMID- 8353351 TI - Percutaneous cholecystostomy for suspected acute cholecystitis in the hospitalized patient. AB - PURPOSE: The authors evaluated the outcome of 49 hospitalized patients with sepsis and possible acute cholecystitis in whom emergency percutaneous cholecystostomy was attempted on 50 occasions. PATIENTS AND METHODS: All cholecystostomy procedures were performed with ultrasound (US) guidance by using either the trocar (n = 35) or the Seldinger (n = 15) technique. Forty of the 50 cholecystostomies (80%) were attempted at the patients' bedside, and 49 of the 50 catheters (98%) were placed successfully. RESULTS: Twenty-five of these patients eventually died of other causes (51%), but there was clinical improvement in 31 of the 49 patients (63%) based on a 72-hour decrease of temperature to less than 37.3 degrees C, normalization of white blood cell count, and/or resolution of abdominal pain. US findings were correlated with clinical response. Clinical improvement occurred most frequently after cholecystostomy in patients with either a distended gallbladder (74%), pericholecystic fluid (80%), or gallstones (92%). Forty-three of the 49 patients underwent cholecystostomy alone (88%), and six required further procedures (12%). There were six complications (12%) including catheter dislodgment (n = 3), hematoma (n = 1), and severe pain (n = 2). No deaths were directly attributed to percutaneous cholecystostomy. CONCLUSION: Percutaneous cholecystostomy performed in septic hospitalized patients is a low-risk procedure that may be helpful in the treatment of some patients with suspected acute cholecystitis. PMID- 8353352 TI - Randomized double-blind clinical trial of celiac plexus block for percutaneous biliary drainage. AB - PURPOSE: This study was undertaken to determine the efficacy of celiac plexus block (CPB) as a method of providing analgesia for percutaneous biliary drainage (PBD). PATIENTS AND METHODS: Thirty-two patients scheduled to undergo PBD were prospectively assigned randomly into placebo (30 mL of normal saline) and treatment (30 mL of 0.25% bupivacaine) CPB groups. Each patient received .03 mg/kg of midazolam for premedication before PBD and had access to a patient controlled analgesia pump during the procedure. The pump was set to deliver 0.2 mg of midazolam and 25 micrograms of fentanyl per dose with a 3-minute lockout time. Vital signs, including heart rate and blood pressure, were continuously monitored during the procedure and recorded for comparison with baseline values. Patients completed a 10-point visual analogue pain scale following completion of their procedure. RESULTS: Patients in the placebo and treatment groups self administered a mean of 2.0 and 1.85 mg of midazolam, respectively (P = .40), and a mean of 247 and 231 micrograms of fentanyl, respectively (P = .40). On a 10 point pain scale, the mean postprocedure versus preprocedure elevation in pain was 2.1 points in the placebo group versus 1.6 points in the treatment group (P = .60). Overall, the degree of satisfaction with the analgesia was equal in both groups. CONCLUSION: This study indicates that CPB is not an effective means of providing additional visceral pain relief over and above that which can be accomplished with self-administered intravenous medication for patients who undergo PBD. PMID- 8353353 TI - Arterial complications of pancreatitis: diagnostic and therapeutic aspects in 104 cases. AB - PURPOSE: A retrospective study of 104 cases of arterial lesions related to pancreatitis was undertaken to examine the diagnostic and therapeutic benefits of arteriography compared with ultrasonography (US) and computed tomography (CT). PATIENTS AND METHODS: Data were acquired from responses to a questionnaire. Eighty-seven patients were men, 17 were women (age range, 21-80 years; mean, 48 years). These lesions were usually revealed by hemorrhage (70 cases), pain (69 cases), or both (46 cases). RESULTS: Arteriography was immediately positive in 90 of 93 patients in whom it was performed, but US and CT may also permit incidental discovery of silent lesions (17 cases). These lesions are often single (90%) and related to an arterial rupture in a pseudocyst (60%) or a pseudoaneurysm (48%). They involved the splenic (42%), the gastroduodenal (22%), and the small pancreatic arteries (25%). Of 32 cases in which embolization was performed, immediate success was achieved in all cases but bleeding recurred in 12 cases (37%). Treatment in 25 patients was a definitive success (78%), and five patients died of hemorrhage (16%). CONCLUSION: Arteriography remains essential for diagnosis of arterial lesions, and embolization may be indicated as a stabilizing preoperative procedure and also for immediately stopping hemorrhage. PMID- 8353354 TI - Percutaneous removal of an embolized Wallstent during a transjugular intrahepatic portosystemic shunt procedure. PMID- 8353355 TI - Delayed Wallstent migration after a transjugular intrahepatic portosystemic shunt procedure: relocation with a loop snare. PMID- 8353356 TI - Percutaneous transfemoral retrieval of a free-floating titanium Greenfield filter with an Amplatz goose neck snare. PMID- 8353357 TI - Increased presaturation pulse gaps in two-dimensional time-of-flight MR angiography: a pitfall in diseased lower extremities. PMID- 8353358 TI - Radiologic diagnosis of superior vena cava laceration. PMID- 8353359 TI - Occlusion of an aberrant right subclavian artery arising from a Kommerel diverticulum. PMID- 8353360 TI - Advances in dietetics and impact on the development of specialty practice areas. PMID- 8353361 TI - Fish-oil-containing diet and platelet aggregation. AB - Current research suggests that a diet high in fish oil may be useful for immunomodulation in hospitalized patients. However, one of the side effects of fish oil is a prolongation of the bleeding time, specifically by reducing platelet aggregability. Although this effect might be beneficial for patients with cardiovascular disease, it would be a potential concern in certain critically ill patients. To address this concern, we conducted a prospective study of platelet aggregation in 16 surgical patients who were randomly assigned to receive either a diet containing 16.5 g of fish oil in 1500 ml (Impact) or usual care (standard enteral formulas devoid of fish oil). Feeding was successfully accomplished in the patient group receiving a diet that provided approximately 14.2 g of fish oil/day for 1 wk without significantly affecting platelet aggregability. Thus, it appears that, over the short term, this dose of fish oil does not alter platelet function in hospitalized surgical patients. PMID- 8353362 TI - Zinc deficiency in elderly patients. AB - Zinc is needed for growth and development, DNA synthesis, neurosensory functions, and cell-mediated immunity. Although zinc intake is reduced in elderly people, its deficiency and effects on cell-mediated immunity of the elderly have not been established. Subjects enrolled in "A Model Health Promotion and Intervention Program for Urban Middle Aged and Elderly Americans" were assessed for nutrition and zinc status. One hundred eighty healthy subjects were randomly selected for the study. Their mean dietary zinc intake was 9.06 mg/day, whereas the recommended dietary allowance is 15 mg/day. Plasma zinc was normal, but zinc in granulocytes and lymphocytes were decreased compared with younger control subjects. Of 118 elderly subjects in whom zinc levels in both granulocytes and lymphocytes were available, 36 had deficient levels. Plasma copper was increased, and interleukin 1 (IL-1) production was significantly decreased. Reduced response to the skin-test antigen panel and decreased taste acuity were observed. Thirteen elderly zinc-deficient subjects were supplemented with zinc, and various variables were assessed before and after zinc supplementation. Zinc supplementation corrected zinc deficiency and normalized plasma copper levels. Serum thymulin activity, IL-1 production, and lymphocyte ecto-5'-nucleotidase increased significantly after supplementation. Improvement in response to skin test antigens and taste acuity was observed after zinc supplementation. A mild zinc deficiency appears to be a significant clinical problem in free-living elderly people. PMID- 8353363 TI - Polydextrose and activities of brush-border membrane enzymes of small intestine in rats and glucose absorption in humans. AB - We investigated the effect of polydextrose, one of the water-soluble non digestible polysaccharides, on the activities of brush-border membrane enzymes of small intestine in rats and on glucose absorption with relation to the thickness of the unstirred water layer in humans. Rats were fed a 5% polydextrose supplemented elemental diet for 2 or 4 wk. The mucosal alkaline phosphatase, maltase, and sucrase activities were measured in the upper, middle, and lower intestine. There was no significant difference between control and polydextrose groups. The potentiometric tube was inserted orally in the jejunum. Glucose absorption was measured by perfusion with the solutions with or without 5% polydextrose. There was no significant difference in the glucose absorption rate or the thickness of the unstirred water layer between control and polydextrose solutions. The increase in viscosity of the polydextrose solution was negligible. This study indicated that polydextrose had no effect on the thickness of the unstirred water layer and did not inhibit glucose absorption in humans. PMID- 8353364 TI - Symptomatic hyperlipasemia after cardiopulmonary bypass: implications for enteral nutritional support. AB - The incidence of pancreatitis after cardiopulmonary bypass is reported as < 0.1%. We report a milder form of pancreatitis characterized by hyperlipasemia and early intolerance to enteral nutrition without overt signs of clinical pancreatitis. A retrospective study was conducted in 72 patients who had received tube feeding. A statistically (p = 0.01) greater incidence of symptomatic hyperlipasemia was noted in post-cardiopulmonary bypass (PCPB) patients (42%, 5 of 12) than in non PCPB patients (0%, 0 of 60). Four of the 5 PCPB patients who developed symptomatic hyperlipasemia received tube feeding into the stomach or duodenum before onset of their symptoms. The overall incidence of PCPB symptomatic hyperlipasemia during the study period was 1.3% (5 of 375). A prospective study was then carried out in 54 PCPB patients. Five patients became critically ill, and 4 of these developed symptomatic hyperlipasemia. Three of the 4 patients had received tube feeding into the stomach or duodenum before the onset of symptoms. In all cases, the symptoms of tube-feeding intolerance were mild and resolved with termination of feeding. This study suggests that critically ill cardiopulmonary bypass patients may be more susceptible to developing symptomatic hyperlipasemia, which is characterized by early intolerance to enteral nutritional support. PMID- 8353365 TI - Nutrition and metabolic management of AIDS during acute illness. AB - Diarrhea, sepsis, and malnutrition in the AIDS population are common. Some authors have predicted length of survival based on malnutrition biomarkers alone (degree of weight loss at presentation and serum albumin). Similarly, the hypothesis that malnutrition creates a vicious cycle that potentiates susceptibility to opportunistic infections may be valid. Consideration should be given to combining aggressive enteral and parenteral support with metabolic support in the acute phase of illness and between bouts of infections to facilitate patient care and to restore lean tissue. A skilled nutritional support service can deliver needed metabolic support along with nutritional support to these patients. In this case, we focused on the challenges of treating a new patient with significant malnutrition associated with AIDS of unknown duration; untreated gastrointestinal pathogens associated with substantial acid-base, electrolyte, and micronutrient deficiency; and systemic sepsis. PMID- 8353366 TI - Carnitine metabolism and human carnitine deficiency. AB - Carnitine in the human body is derived from the intake of preformed dietary carnitine and biosynthesized carnitine, stemming from the metabolism of lysine and methionine. Carnitine is synthesized in liver and kidney, stored in skeletal muscle, and excreted mainly in urine. Carnitine has two main functions, i.e., transporting long-chain fatty acids into the mitochondrial matrix for beta oxidation to provide cellular energy and modulating the rise in intramitochondrial acyl-CoA/CoA ratio, which relieves the inhibition of many intramitochondrial enzymes involving glucose and amino acid catabolism. Thus, the main consequence of carnitine deficiency is impaired energy metabolism. Human carnitine deficiency can be either hereditary or acquired. Hereditary carnitine deficiency can be grouped into three clinical entities: myopathic carnitine deficiency, systemic carnitine deficiency, and organic acidurias. Acquired carnitine deficiency is due to inadequate intake, increased requirement, and increased loss of carnitine. The definite diagnosis of carnitine deficiency is based on the determination of free- and acylcarnitine levels in serum, urine, and/or tissues. The estimated safe and adequate daily carnitine intake for adults is 150-500 mumol/day whereas pharmacological doses of carnitine are required for the treatment of hereditary carnitine deficiency. PMID- 8353367 TI - Carbohydrate metabolism and requirements for nutritional support: Part III. PMID- 8353368 TI - Risk versus benefit of fish oil for hospitalized patients. PMID- 8353369 TI - The elusive enigma of post-cardiopulmonary bypass pancreatitis and the role of early enteral feeding. PMID- 8353370 TI - Glucose/fatty acid cycle: regulatory system. PMID- 8353371 TI - Clinical problem of hospital malnutrition. PMID- 8353372 TI - Clinical evaluation of serum ferritin as index of iron stores. PMID- 8353373 TI - Beneficial effect of L-arginine in collagen vascular diseases: a role for nitric oxide. PMID- 8353374 TI - Errors in hypothesis testing and power. PMID- 8353375 TI - "An apple a day keeps the doctor away" and other health claims. PMID- 8353376 TI - Interactions of nutrition and ventilation. PMID- 8353377 TI - Metabolism in fever. 1928. PMID- 8353378 TI - The 1992 John M. Kinney International Award for Nutrition and Metabolism. Dietary L-lysine and calcium metabolism in humans: background. PMID- 8353379 TI - Analysis for atrazine in fortified cornmeal and corns using a commercially available enzyme immunoassay microtiter plate. PMID- 8353380 TI - Aldrin contamination at a school in South Australia. PMID- 8353381 TI - Malathion leakage from fruit fly male-annihilation traps on Kauai, Hawaii. PMID- 8353382 TI - Trace element analysis of the traditional medicine, Jamu. PMID- 8353383 TI - Occupational exposures to PAHs measured with UV derivative spectroscopy corrected for advective and gaseous losses. PMID- 8353384 TI - Bile duct hyperplasia and transient liver parenchymal cell alteration by methylisocyanate. PMID- 8353386 TI - Bacterial enumeration and mercury volatilization in deep subsurface sediment samples. PMID- 8353385 TI - Comparison of phytooestrogen-coumestrol and oestrone effects on the liver membranes insulin receptors in ovariectomized female rats. PMID- 8353387 TI - Influence of some growth regulators and cations on inhibition of chlorophyll biosynthesis by lead in maize. PMID- 8353388 TI - Elemental and morphological analyses of atmospheric particles from southwestern part of Mexico City. PMID- 8353389 TI - Transplanted aquatic mosses for monitoring trace metal mobilization in acidified streams of the Vosges Mountains, France. PMID- 8353390 TI - Validation of a paramagnetic particle-based ELISA for the quantitative determination of carbaryl in water. PMID- 8353391 TI - Pesticide residues in cropland soils and shallow groundwater in Punjab Pakistan. PMID- 8353392 TI - Hematological values of rainbow trout, Oncorhynchus mykiss W., exposed to premetallized dyes. PMID- 8353393 TI - Pollution of the River Niger and its main tributaries. PMID- 8353394 TI - Chronic toxicity of Pydraul 50E to lake trout. PMID- 8353395 TI - Cadmium and lead uptake by red swamp crayfish (Procambarus clarkii) of Louisiana. PMID- 8353396 TI - Toxicity of cadmium and lead to juvenile red swamp crayfish, Procambarus clarkii, and effects on fecundity of adults. PMID- 8353397 TI - Histopathological effects of sublethal exposure to phenol on two variously pre stressed populations of bullhead (Cottus gobio L.). PMID- 8353398 TI - Metal leaching from experimental coal fly-ash oyster cultch. PMID- 8353399 TI - Acyclovir for varicella in immunocompetent patients. PMID- 8353400 TI - Solitary versus multiple cholesterol gallbladder stones. Mechanisms of formation and growth. AB - The development and growth pattern of solitary and multiple cholesterol gallbladder stones was defined using cholecystography in a prospective study of 48 patients whose initial cholecystograms indicated a stone-free gallbladder and who developed gallstones within the subsequent 5 years. Radiological observations performed over 365 patient-years were complemented by macroscopic examination, radiograms, scanning electron microscopy, and chemical analysis of gallstones from these and other patients obtained at cholecystectomy. Solitary gallstones were found to develop after a precursor phase of over 2 years during which free floating crystal laminae of cholesterol formed. These laminae subsequently aggregated loosely and underwent external compaction and internal remodeling by movement of cholesterol molecules to form compact spheroids. A single lamina was observed to function as a nucleus for the development of a solitary stone shaped as an ellipsoid. About 10% of solitary stones were found to have a solitary pigment stone in their center. In contrast, multiple cholesterol gallstones formed without a precursor phase. Innumerable, very thin cholesterol crystals appeared which very abruptly aggregated to form spheres of up to 1 mm in diameter. Within 3 months a second aggregation took place in which these spheres colaesced to form mulberry stones. Mulberry stones in turn were transformed either to faceted stones (if many were present in the gallbladder) or to barrel stones (if few were present) over a period of 3 years. It is proposed that temporary occlusion of the cystic duct leads to supersaturation of bile with calcium bilirubinate and/or calcium carbonate which in turn promotes deposition of either or both of these calcium salts on the surface of single or multiple gallstones. For multiple gallstones, this process or the deposition of additional cholesterol crystals seals the gallstone surface and is followed by metamorphosis of the stone center. PMID- 8353401 TI - Treatment of acute postoperative renal failure after liver and heart transplantation by urodilatin. PMID- 8353402 TI - Tumor-associated antigens in effusions of malignant and benign origin. AB - We determined the concentration and effusion/serum ratio of mucin-like carcinoma associated antigen (MCA) in comparison to carcinoembryonic antigen, carbohydrate antigen 19-9, cancer antigen 125, and cancer antigen 15-3 in 80 sera and 99 effusions from 64 patients with histologically confirmed malignancies (4 patients out of this group showed various effusions simultaneously, which were analyzed separately) and 31 patients with various nonneoplastic diseases. Tumor cells were detected by cytological examination in 41 effusions (60.3%) from patients with neoplastic diseases, while in another 27 cases this method failed to demonstrate the malignant origin of the effusion. Of the cytological "positive" malignant effusions 90% were also correctly identified by an elevated MCA concentration at a cutoff level of 10 U/ml, whereas only one effusion of benign origin (3%) showed a slightly elevated MCA concentration of 10.5 U/ml. In 33% of cytologically "negative" effusions of patients with neoplastic diseases, the MCA concentration was also elevated, with a maximum of 453 U/ml. Increased MCA levels in cytologically confirmed malignant effusions were not restricted to metastatic breast cancer. All 17 cytologically "positive" "non-breast cancer" effusions were correctly identified by their MCA concentrations. None of the other tumor markers reached this high sensitivity at the same level of specificity. The ratio of effusion/serum concentration of all tumor markers as well as the concentration of cancer antigen 125 in effusions was of little diagnostic value. Our results indicate that the MCA concentration in an effusion correlates very closely with its malignant origin and is superior to all the other antigens tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353403 TI - Repertoires of autoantibodies against homologous eye muscle in ocular and generalized myasthenia gravis differ. AB - If weakness of the eye muscles remains the only symptom of myasthenia gravis (MG) for more than 2 years, the condition is operationally defined as ocular MG (OMG). A number of clinical, genetic, and immunological differences between this variant and generalized MG (GMG) have been described. We analyzed repertoires of autoantibodies against proteins of skeletal and extraocular muscle in sex- and age-matched groups of patients with either GMG or OMG (n = 10 in each group). All GMG sera detected a group of three proteins larger than 200 kDa which were not detected by any of the OMG sera. Two components with apparent molecular weights of 50 and 60 kDa were stained by seven of the ten OMG sera but by none of the GMG group. These antigens are probably soluble, cytoplasmatic proteins of the eye muscle. OMG sera, furthermore, detected a protein of about 45 kDa in the pellet fraction of eye muscle but failed to do so after adsorption with skeletal muscle fractions. We conclude that OMG and GMG sera contain autoantibodies of different specificities. Our findings further support immunological heterogeneity in MG. PMID- 8353404 TI - Ultrastructural study on human lung in alveolitis versus pulmonary fibrosis. AB - Lung specimens of 21 patients with diffuse interstitial lung disease were examined. The present ultrastructural study outlines the topography and distribution of inflammatory changes in the interstitium, endothelium, and in pneumocytes and phagocytes. Alveolitis is characterized by marked regenerative activity of type II pneumocytes (cuboid metaplasia), intraluminal macrophage accumulation, endothelial swelling, multilamination of the endothelial basement membrane, pericapillary edema, and primarily by cellular infiltrates in the interstitial space. The most prominent feature of the interstitium in pulmonary fibrosis is the lack of immunoinflammatory cells. In some areas there is a marked absence of alveolar lumen while only a small number of macrophages are present in the remaining alveolar lumen. Most of the capillaries in the fibrous septum have been destroyed. Ultrastructural studies of lung biopsies in patients with diffuse interstitial lung disease allow the differentiation between alveolitis and pulmonary fibrosis and thus contribute to a therapeutic decision. PMID- 8353405 TI - Ergometer exercise in myoadenylate deaminase deficient patients. AB - Three patients with primary myoadenylate deaminase deficiency were subjected to exercise on a bicycle ergometer at 125 W for 30 minutes. Blood samples prior to, during, and at the end of exercise were analyzed for lactate, ammonia, and hypoxanthine. In addition, urinary hypoxanthine excretion was measured. In these patients the serum lactate level increased to concentrations between 7.9 and 9.0 mmol/l at the end of exercise whereas the mean lactate level in nine control subjects at the end of exercise was 3.3 mmol/l (range 1.1-8.1 mmol/l). There was no difference to control subjects in the exercise-induced increase in plasma levels of ammonia and hypoxanthine or in the increase in urinary hypoxanthine excretion. The findings support the hypothesis of a reduced substrate supply to the citric acid cycle in myoadenylate deaminase deficiency. The normal formation of ammonia and hypoxanthine excludes a marked loss of adenine nucleotides in working muscles in these patients. PMID- 8353406 TI - Hypoxia of diabetic feet with abnormal arterial blood flow. AB - Necrotic ulcers of the feet are a dangerous complication of the diabetic foot syndrome. Besides peripheral vascular disease (PVD) peripheral neuropathy is an important factor in the pathogenesis of necroses. We examined whether the reserve of circulation during reactive hyperemia at the feet of patients with type I diabetes mellitus with abnormal blood flow (n = 17) is decreased compared with diabetic (n = 14) and nondiabetic (n = 20) controls. Further we analyzed whether there is a correlation with the oxygen supply of the foot. PVD was excluded by clinical check-up, oscillography, and Doppler ultrasound. The reserve of circulation of the foot was measured during reactive hyperemia and oxygen supply of the foot by oximetry. Abnormal blood flow of the foot was diagnosed by the pulsation index. On examination it was found that the reserve of circulation of diabetic feet with abnormal blood flow is about 52% less than in diabetic and about 50% less than in nondiabetic controls (P < or = 0.005). The decreased reserve of circulation correlates with the oxygen supply of the feet; this is about 21% less compared to diabetic feet with normal blood flow and about 16% less in comparison to nondiabetic feet. The present study shows that diabetic feet suffer from disturbed circulation although there is no evidence of PVD. This disturbed circulation is correlated with a decreased oxygen supply of the feet. Hypoxia during strain could be of great importance in the pathogenesis and treatment of necrotic ulcers of diabetic feet. PMID- 8353407 TI - PHLECO: a multicenter study of the fate of 1647 hospital patients treated conservatively without fibrinolysis and surgery. AB - The PHLECO Study (phlebothrombosis conservative therapy) is a multicenter investigation of patients with deep vein thrombosis receiving conservative nonfibrinolytic hospital treatment. A second study (part II: PHLEFI, phlebothrombosis fibrinolytic treatment) to be published later deals with the outcome of fibrinolytic therapy. In both studies the incidence of life threatening sequelae, such as pulmonary embolism, is of major interest. The 49 medical departments participating in the study mailed the relevant data to the Duisburg Coordination Center for further data analysis and the following information was gained: (a) In descending order of frequency, the clinical conditions of thrombosis were: immobility, postoperative status, malignancy, hormone treatment, posttraumatic conditions, and pregnancy. (b) In descending order of frequency, the sites of thrombosis were: femoral vein, calf vein, iliac vein, popliteal vein, and subclavian vein. Left-sided thrombosis predominated in the iliac and subclavian vein groups. (c) In descending order of frequency, the treatment regimens employed were: intravenous heparin+oral anticoagulants, intravenous heparin+subcutaneous heparin, intravenous heparin alone, subcutaneous heparin alone, intravenous heparin+subcutaneous heparin+oral anticoagulants, subcutaneous heparin+oral anticoagulants, intravenous heparin+platelet aggregation inhibitors. (d) The average hospital stay was 23.7 +/- 15.6 days. No correlation existed between duration of hospital stay and particular types of therapy. (e) The incidence of nonfatal pulmonary embolism was 16.1% while that of fatal pulmonary embolism was 2.33%. (f) Women outnumbered men in the group with fatal pulmonary embolism, and the death rate among older patients was higher than that among younger patients. (g) Patients with fatal pulmonary embolism had a shorter history of thrombosis than patients in the unselected cohort (patients with and without pulmonary embolism).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353408 TI - Clinical pharmacology in the 1990s: a personal perspective. PMID- 8353409 TI - Compliance and adverse drug reactions: a prospective study with ethinylestradiol using continuous compliance monitoring. AB - This study examined the relationship between adverse reactions and patient compliance with ethinylestradiol at 40 micrograms twice daily versus 20 micrograms four times daily. In a randomized study 61 female patients with primary infertility were prescribed the drug twice daily (n = 31) or four times daily (n = 30). Ethinylestradiol was administered for 7 days before the sperm cervical mucus penetration-test was performed for hormonal standardization of the cervical mucus quality. Drug compliance was measured by continuous monitoring using the Medication Event Monitoring System. Two parameters were evaluated: percentage of prescribed doses taken (administration compliance) and adherence to the prescribed dose schedule (regimen compliance, number of days with two or four dosing events recorded). Adverse drug reactions were assessed using a standardized questionnaire. Fourty-four women experienced side effects, of which 81% were rated by patients as being mild. Patient compliance was higher with the twice daily than with the four times daily regimen: 85% versus 65% prescribed doses taken (P < 0.05). There was no significant difference in compliance comparing patients with and without adverse reactions (82% versus 72%, respectively), but compliance was lower and more irregular with at least 3 versus one or two adverse reactions reported: 54% versus 84% in administration compliance and 31% versus 58% in regimen compliance (P < 0.05). Compliance was also lower in patients with nausea and vomiting than in those without these symptoms, 59% versus 91% and 34% versus 66% (P < 0.005), respectively, and lower with moderate or severe compared to mild side effects; 48% versus 85% and 25% versus 59% (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353411 TI - Mammalian chromosome structure. AB - The DNA sequences that are necessary for the formation of a functional mammalian chromosome are thought to be the origins of replication, the telomeres and the centromere. Telomere structure is now well understood, with the functional element characterized as the motif (TTAGGG)n. The structures of the DNA regions that contain origins of replication and a centromere are known, but the functionally important elements within these regions are still only poorly defined. PMID- 8353412 TI - Trisomy in humans: incidence, origin and etiology. AB - Molecular studies conducted over the past year have demonstrated the importance of aberrant genetic recombination in the etiology of several human trisomies, and have begun to shed light on the basis of the association between advancing maternal age and trisomy. Preliminary studies of gametes using fluorescence in situ hybridization indicate that this will be a useful approach in the analysis of human non-disjunction. PMID- 8353413 TI - Trinucleotide repeats and genome variation. AB - The recent cloning of several disease genes has identified the instability of trinucleotide repeats as a fundamental mechanism for variation within the human genome. This mutation mechanism explains the unique inheritance characteristics of the diseases it causes, and there is a significant potential that this mechanism is involved in the pathogenesis of other, as yet uncharacterized, genetic diseases. PMID- 8353410 TI - Genetics of cancer predisposition and progression. AB - The development of human cancer is a multistep process that entails a progressively more malignant phenotype through the evolution of cellular subsets with increasing numbers of genetic alterations. Here we review the molecular genetics of human cancer predisposition and progression and describe paradigmatic cancer types and cancer syndromes. We also briefly consider the future impact of molecular biology on cancer diagnosis and treatment. PMID- 8353414 TI - Wilms' tumour gene and function. AB - The Wilms' tumour gene, WT1, encodes a protein with four zinc fingers that is probably a transcription factor. In humans, WT1 mutations can lead to childhood kidney tumours and to developmental defects of the kidney and gonad. The WT1 gene may have a role in the mesenchyme to epithelial switch in a range of mesodermally derived tissues. Furthermore, growth-factor genes may be targets for repression by the WT1 protein during development. WT1 is the first example of a tumour suppressor gene with a specific developmental role. PMID- 8353415 TI - Microsatellite polymorphisms and the genetic linkage map of the human genome. AB - The use of simple sequence repeats as polymorphic genetic markers has significantly facilitated the construction of reference maps of the human chromosomes and the mapping of mendelian genetic diseases. These markers display major advantages over other systems, including restriction fragment length polymorphisms and satellites, but also have some limitations. PMID- 8353416 TI - Integrating maps of human chromosome 11. AB - The past year has seen major advances in our understanding of chromosome structure, driven by technology that allows the rapid construction of physical and genetic maps. Information on the structure and organization of human chromosome 11 is rapidly being accumulated as a result of these developments. PMID- 8353417 TI - Integrating maps of chromosome 16. AB - The recently published, detailed cytogenetic-based physical map of chromosome 16 has the highest resolution of any autosomal cytogenetic map thus far constructed. The genetic map has been integrated with the cytogenetic map to facilitate the regional localization of disease genes by linkage. Disease genes for tuberous sclerosis, familial Mediterranean fever, Rubinstein-Taybi syndrome and Morquio A syndrome have now been assigned to chromosome 16. The search for the adult polycystic kidney disease gene has recently been narrowed to the analysis of candidate loci on chromosome 16, and localization of the gene determining juvenile Batten disease has been further refined by disequilibrium mapping. PMID- 8353418 TI - Deletions of human chromosome 22 and associated birth defects. AB - Investigations into the genetic basis of DiGeorge syndrome have shown that in the majority of cases there are DNA deletions from the long arm of chromosome 22, at 22q11. Similar deletions are now known to be present in a wide range of conditions with overlapping clinical features, and are an important cause of familial congenital heart defect. Deletions within 22q11 have also been identified in individuals with no clinical complications. PMID- 8353419 TI - Charcot-Marie-Tooth disease type 1A: mutational mechanisms and candidate gene. AB - Charcot-Marie-Tooth disease type 1A, the most common inherited peripheral neuropathy, is associated with a submicroscopic DNA duplication of 1.5 Mb that can arise de novo, and which is flanked by a > 17 kb mosaic repeat. The PMP22 gene, encoding a peripheral myelin protein, maps within the duplication. In a subset of Charcot-Marie-Tooth patients, point mutations can occur within the gene. Thus, the alternative mechanisms of overexpression of PMP22 and structural alterations in the protein encoded can cause the disease phenotype. PMID- 8353420 TI - Genomic imprinting and candidate genes in the Prader-Willi and Angelman syndromes. AB - The Prader-Willi and Angelman syndromes are now well established as the paradigm of genomic imprinting in human disease. Over the past year, much has been learnt about the mechanisms by which these syndromes arise and molecular diagnostics for the majority of patients are now available. Mouse models for aspects of the syndromes have been established, and the first association between a gene, located in chromosome 15, at 15q11-q13, and a phenotype (albinism) has been proven. Large parts of the critical regions have been cloned and at least six genes identified. Three genes or DNA sequences may be imprinted: two of these demonstrate DNA-methylation imprints and one is functionally imprinted in mouse. While the molecular mechanism of imprinting is not yet understood, it is beginning to yield its secrets to DNA methylation, replication, and chromatin structure studies of the phenomenon. PMID- 8353421 TI - Mitochondrial disorders. AB - Several different types of mitochondrial DNA mutations have now been identified in a wide spectrum of human disorders. There is some correlation between certain of these mutations and the patient's clinical phenotype, although this relationship is not absolute. The mechanisms by which these mutations produce respiratory chain deficiency and the dysfunction of different tissues are unknown. It is becoming increasingly likely that the nuclear genome plays an important role in the expression of the mitochondrial DNA mutation and the pathogenesis of these diseases. PMID- 8353422 TI - Polygenic disease. AB - Considerable success is now being achieved in defining genetic susceptibility loci in polygenic disease. In particular, new susceptibility loci have been identified in hypertension, type I and type II diabetes, asthma and malaria infection. The approaches and tools for mapping such susceptibility determinants are becoming more clearly defined and the identification of further susceptibility genes is likely to be in demand in the near future. PMID- 8353423 TI - Mammalian DNA-repair genes. AB - The sequence and functional homology of certain genes between mammalian and non mammalian eukaryotes has facilitated significant advances in our understanding of mammalian DNA repair. Several novel DNA damage and repair genes have been identified by using a variety of approaches. Study of these genes will lead to an increased understanding of the biological consequences of aberrant DNA maintenance in humans and other species. PMID- 8353424 TI - Biochemical genetics: examples of life after cloning. AB - The blend of biochemistry and molecular biology required to understand the pathogenesis of genetic disease is assuming an increasing role in research. We review three example of this inevitable post-cloning trend: first, the surprising relationship between mice with albino deletions and human hereditary tyrosinemia type I; second, the discovery that choroideremia is due to defect in prenylation; and third, fibrillin mutations in the Marfan syndrome. PMID- 8353425 TI - Dystrophin and related proteins. AB - During the past year significant progress has been made in understanding how dystrophin deficiency leads to muscle cell necrosis in Duchenne muscular dystrophy and Becker muscular dystrophy. Dystrophin interacts with a glycoprotein complex spanning the muscle sarcolemma, effectively linking the actin cytoskeleton to the extracellular matrix. The carboxyl terminus of dystrophin is required for glycoprotein binding. Interestingly, at least three mRNAs transcribed from the distal end of the DMD gene in tissues other than muscle have been shown to encode this domain. Deficiency of a second component of the dystrophin-associated glycoprotein complex has been shown to occur in another muscle-wasting disorder, severe childhood autosomal recessive muscular dystrophy. Sequence analysis of the entire cDNA for the autosomal dystrophin-related protein utrophin has shown that dystrophin and utrophin are closely related. Furthermore, both of these proteins have been shown to bind to the same or a similar glycoprotein complex in muscle. PMID- 8353426 TI - Genetic control of gastrulation in the mouse. AB - In the past, understanding of the process of gastrulation in the mouse has primarily been based on morphological analyses. Recently, a number of molecules have been implicated in mesoderm induction and axis formation in Xenopus, and several of these exhibit unique patterns of expression during mouse gastrulation. These gene-expression data, together with fate mapping, ectopic expression experiments and mutational analysis, will now facilitate studies on the functional aspects of gastrulation in the mouse. PMID- 8353427 TI - Gene therapy: adenovirus vectors. AB - The past year has seen a proliferation in the use of recombinant, replication defective adenoviruses for experimental models of gene therapy. The fact that adenovirus infects most cell types with no requirement for cell division, combined with the high titers and high efficiency of gene transfer obtainable with recombinant adenovirus, make it a promising system for in vivo human gene therapy. PMID- 8353428 TI - Mammalian genetics. PMID- 8353429 TI - Noonan's syndrome with keratoconus and optic disc coloboma. AB - We report the case of a 14-year-old girl with multiple findings characteristic of Noonan's syndrome, including short stature, mild mental retardation, facial, skeletal and renal abnormalities. In addition, ophthalmic examination revealed a keratoconus in the left eye and a right optic disc coloboma. To date, only two cases of Noonan's syndrome with keratoconus have been reported, and this is the second case of this syndrome with optic disc coloboma. To our knowledge, this is the first report of Noonan's syndrome associated with unilateral keratoconus and contralateral optic disc coloboma. In view of the large number of patients with Noonan's syndrome reported to date and the rarity of these ocular abnormalities, it is most likely that this association is fortuitous. Ocular findings reported in patients with Noonan's syndrome are reviewed. PMID- 8353430 TI - An anatomic index for the severity of ocular injuries. AB - Ocular injuries are a frequent cause of monocular blindness and cause disfigurement and discomfort. We developed a measure of severity for eye injuries using a multi-attribute utility (MAU) model. The severity index scoring was applied to eye injuries that presented at hospitals in Wisconsin, U.S.A. The resulting distribution of severities was compatible with that seen by general eye care physicians. A severity scale provides a means of comparing the severity of injuries from a wide variety of traumatic sources (e.g. automobile crashes, combat injuries, occupational accidents, etc.) and is useful in evaluating preventive and public health measurements. PMID- 8353431 TI - Intraocular levels of cefuroxime in inflamed rabbit eyes. AB - The pharmacokinetics of cefuroxime was studied in the inflamed rabbit eye employing subconjunctival, intravitreal and combined intravitreal-intravenous routes of administration to study the intraocular levels and the duration of minimum inhibitory concentrations (MIC) of the antibiotic in the vitreous and in the aqueous. A standard inoculum of viable S. aureus was injected into the vitreous of 36 pigmented rabbits to establish experimental endophthalmitis. A biological method was used for the antibiotic assay. Penetration of systemically and subconjunctivally administered-cefuroxime into the inflamed vitreous was poor. Intraocular inflammation increased the clearance of the intravitreally injected cefuroxime. A dose of 75 mg subconjunctivally produced levels in the aqueous far exceeding MIC for over six hours. Penetration of intravitreally injected cefuroxime into the aqueous was poor, inconsistent and short lasting. Following a single intravitreal injection of 1000 micrograms cefuroxime, levels exceeding the MIC for common ocular pathogens persisted in the vitreous for at least 24 hours but supplementation with intravenous cefuroxime neither increased the intraocular levels nor delayed the clearance of the intravitreally injected antibiotic. PMID- 8353432 TI - Corneal sensitivity after penetrating keratoplasty. AB - In order to determine corneal sensitivity after penetrating keratoplasty, 71 corneal transplants and their recipient beds were tested using the Cochet-Bonnet esthesiometer. The periods from surgery to examination were two weeks to 15 years. When the test results were divided into six groups according to the postoperative period, correlation analysis revealed a progressive improvement of sensitivity in the central and peripheral graft as well as in the recipient cornea. Only one graft had normal central sensitivity at 24 months; 36 grafts were completely anesthetic while 35 grafts had some level of sensitivity at the time of last clinical testing. Age, preoperative diagnosis or graft size were not correlated with the recovery of sensitivity. The extent and time of reinnervation in corneal grafts varied in individual patients. PMID- 8353433 TI - Silicone intubation as an alternative to dacryocystorhinostomy for nasolacrimal drainage obstruction in adults. AB - Silicone tubing was used to repair the patency of the nasolacrimal drainage system in 115 patients (four bilaterally) with chronic nasolacrimal duct obstruction. The patients were over 20 years old and 16 were men and 99 women; 46% presented an uncomplicated obstruction with epiphora and 54% presented additional signs of chronic dacryocystitis. We used the technique of Quickert and Dryden with modifications. The silicone tube remained for a mean of 5.5 months (+/- 2.5 SD). After removal of the tube the follow-up ranged from 6 to 42 months (mean +/- SD: 16 +/- 9). Patency was maintained in 89% of cases with uncomplicated obstruction and in 69% of those with chronic dacryocystitis (total success rate 78%). We can therefore recommend silicone intubation of the lacrimal drainage system as an alternative to dacryocystorhinostomy (DCR), in adults with obstruction of the nasolacrimal duct. In addition, unlike DCR this technique is bloodless and the operation takes less time. PMID- 8353434 TI - Evaluation of efficacy and safety of ciprofloxacin ophthalmic solution versus chloramphenicol. AB - The results of this clinical study demonstrate that ciprofloxacin ophthalmic solution 0.3% is as safe and as effective as 0.5% chloramphenicol ophthalmic solution in the treatment of conjunctivitis and blepharitis of bacterial aetiology. Both agents achieved microbiological improvement rates in excess of 90% after 1 week's treatment. On ciprofloxacin 93.5% of patients were judged clinically cured or improved versus 84.6% on chloramphenicol after 1 week. There were no serious adverse affects. One patient in each group suffered drug-related side-effects (chemosis, erythema) which resolved on discontinuation or changing of therapy. Cirpofloxacin is not associated with the rare, but serious, side effect of aplastic anaemia which is associated with chloramphenicol use. On the evidence of this study ciprofloxacin would appear to be an appropriate agent for general use as a topical ophthalmic formulation. PMID- 8353435 TI - Dopamine and its metabolites in human tears. AB - Dopamine is known to stimulate ion transport in the corneal epithelium. Since epithelium is in contact with tears, we searched for dopamine and its metabolites in tears. Twenty normal subjects participated in this study. Twenty microliters of tears were collected in capillary tubes after trigeminal stimulation and immediately analyzed using high-performance liquid chromatography with electrochemical detection. Dopamine and two of its metabolites, 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were identified and measured. The mean concentration of dopamine was 8.9 +/- 5.1 ng/ml; DOPAC, 2.2 +/- 1.6 ng/ml; and HVA, 0.55 +/- 0.4 ng/ml. These results permit us to suggest that dopamine is deaminated by monoamine oxidase, then methylated by catechol-O-methyltransferase and that catabolism occurs in the lacrimal gland and perhaps in corneal epithelium. Finally, part of the dopamine involved in ion transport may come from tears. PMID- 8353436 TI - Hyperbaric oxygenation combined with nifedipine treatment for recent-onset retinal artery occlusion. AB - We describe the results of early hyperbaric oxygenation combined with nifedipine treatment for central retinal artery occlusion, and explain the results pathophysiologically. We report four cases in which hyperbaric oxygenation therapy was applied in combination with nifedipine, eyeball massage, and glycerol for the treatment of central retinal artery occlusion. In two of the cases in which therapy was started less than 100 minutes after the acute onset of visual loss and one case in which therapy was started during the course of central arterial occlusion, considerable improvement in visual acuity was observed, while in the fourth case in which therapy was started six hours after the acute onset of visual loss, no improvement appeared. We conclude from these results that hyperbaric oxygenation therapy has a beneficial effect on the final visual outcome of central retinal artery occlusion, provided it is applied early enough. Further investigation is needed to fully define the nature and terms of this beneficial effect. PMID- 8353437 TI - Fibrin reaction after extracapsular cataract extraction: a statistical evaluation. AB - As part of a retrospective study, 1056 eyes of 940 patients who had undergone extracapsular cataract surgery and posterior chamber IOL implantation were studied using statistical methods (chi-squared test). We studied the presence of fibrin reaction in three subgroups: diabetics without retinopathy (102 eyes), previously operated for primary open angle glaucoma "POAG" (78 eyes) and exfoliation syndrome without glaucoma (43 eyes). The results were compared for these three groups and for a group of normal individuals. The incidence of fibrin reaction was 13.7% in the diabetics, 44.8% in the group of previously operated POAG and 27.9% in the group of exfoliation syndrome without glaucoma. All the groups studied had this complication much more often than the controls (p < 0.0001). The incidence among previously operated eyes for POAG was higher than in diabetic eyes without retinopathy (p < 0.0005) and in exfoliation syndrome without glaucoma eyes (0.05 < p < 0.1). Fibrin reaction was more common in exfoliation syndrome without glaucoma than in diabetic eyes without retinopathy (p < 0.05). PMID- 8353438 TI - Spontaneous hyphaema arising from a strand of persistent pupillary membrane. AB - A case is reported of spontaneous hyphaema arising from a persistent strand of vascularised pupillary membrane. This strand, and an aneurysmal dilatation from which haemorrhage occurred, were illustrated by fluorescein angiography. The embryogenesis of pupillary membranes is discussed and the literature is reviewed with reference to spontaneous hyphaema. PMID- 8353439 TI - History of brain stem surgery. AB - The earliest surgical procedures on the brain stem parenchyma were directed at sectioning specific fiber pathways to alleviate pain. Subsequently, some tumors, abscesses, and vascular lesions that displace rather than invade the parenchyma have been successfully removed. Future advances depend on the ability to preserve and restore neural function in operated tissue. PMID- 8353440 TI - Surgical anatomy of the brain stem. AB - Successful surgery within the brain stem parenchyma demands precise knowledge of the surface anatomy, relationship between surface and deep structures, microscopic anatomy, and functional anatomy of the brain stem. Emphasis on correlative knowledge of these aspects of brain stem anatomy will improve the success of brain stem surgery. PMID- 8353441 TI - Experimental brain stem surgery. AB - Few models of experimental brain stem surgery exist in the literature. Often, experiments were devised in the animal laboratory after a similar surgical procedure already had been attempted on human subjects. Many of the experiments referenced in this article were performed with the goal of delineating neuroanatomic or neurophysiologic pathways, and then this information was used to develop new techniques in the clinical arena, such as BAERs. A new model for brain stem hemorrhage is presented in this article as well as a comparison of the outcomes of open surgical evacuation, stereotactic aspiration, and control animals with pontine hemorrhages. PMID- 8353442 TI - Assessing brain stem function. AB - Intraoperative neurophysiologic monitoring provides objective measures of nervous system function that are of value when operating in proximity to the brain stem. Real-time measurements of function can be correlated to operative manipulations in order to reduce the risk of damage in critically important regions. Techniques for evaluating brain stem function clinically and electrophysiologically are presented along with their applications during surgery of the brain stem. PMID- 8353443 TI - Diagnostic imaging of the brain stem. AB - The small size of the brain stem, its location between the petrous pyramids, and the density of neuroanatomic structures in its substance make imaging of the brain stem one of the most challenging aspects of diagnostic neuroradiology. The relative value of CT, MRI, and angiography in the diagnosis of various brain stem lesions is reviewed. The contributions that can be made by more advanced diagnostic and functional imaging techniques are presented. PMID- 8353444 TI - Surgical approaches to the brain stem. AB - During the last decade there has been a remarkable increase in the interest of neurosurgeons in surgical approaches along the base of the skull. A plethora of different approaches, most of which involve a slight variation of a previously described approach, have been reported in the recent literature, frequently with proprietary claims of originality. This increased confidence of the neurosurgeon in approaching lesions along the base is due to our renewed interest in the anatomy of the skull base and our willingness to collaborate with some of our colleagues in otorhinolaryngology who have concentrated their surgical anatomic studies in this area for years. It is clear that the neurosurgeon who currently undertakes surgery of complex lesions involving the base of the skull, the brain stem and the associated cranial nerves and arteries must have a thorough understanding of this anatomy and frequently must engage the help of an ear-nose and-throat colleague to enhance his or her own expertise with these complex cases. The emerging principle is that whenever possible, exposure should be obtained through carefully planned bone removal along the base rather than through brain retraction. It needs to be emphasized, however, that most of the complex approaches alluded to in the preceding sections are necessary only when the surgeon is dealing with extrinsic lesions, neoplastic or vascular, that only secondarily affect the brain stem itself. Almost all intrinsic lesions of the brain stem can be accessed through one of the more traditional approaches with which all neurosurgeons should be fully familiarized. When the lesion involves or points toward the floor of the fourth ventricle, a standard suboccipital approach through the vermis suffices. Lesions presenting in the cerebellopontine angle or the lateral pons may be safely approached through a standard retromastoid craniectomy. A more direct (perpendicular) access can be obtained by a standard subtemporal-transtentorial approach when the lesion is high and lateral, by a combined subtemporal-suboccipital approach when the lesion extends more inferiorly, and by a combined subtemporal-presigmoid approach for the more anteriorly located lesions. Anterior or anterolateral lesions of the highest aspect of the pons or of the mesencephalon can be readily accessed by the pterional-anterior temporal approach or by a standard subtemporal approach. Dorsal mesencephalic lesions require a supracerebellar/infratentorial approach or, when they extend more inferiorly, an occipital transtentorial approach. When the ventral aspect of the lower brain stem is involved, the lateral suboccipital approach works well.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8353445 TI - Intraparenchymal brain stem radiosurgery. AB - Stereotactic radiosurgery using the gamma unit has been used to manage patients with brain stem tumors or vascular malformations as an alternative to microsurgical resection. Whether associated with the pial or ependymal brain stem surface or within the brain stem parenchyma proper, radiosurgery provides relatively safe and effective management. Radiosurgery is a valuable alternative for many patients with pathologic lesions of the brain stem and may represent the only surgical option for some patients. PMID- 8353446 TI - Primary pontine hemorrhagic events. Hemorrhage or hematoma? Surgical or conservative management? AB - The pathophysiology of primary pontine hemorrhagic events is unclear, but the traditional classification of hemorrhage or hematoma does not have either pathologic or clinical support. Reported cases of brain stem hemorrhage suggest that patients who suffer progressive deterioration from hemorrhagic pontine lesions may benefit from surgery even if they eventually become comatose, whereas those who suddenly lose consciousness and have profound neurologic deficit probably will not survive. PMID- 8353447 TI - Arteriovenous malformations of the brain stem. AB - Arteriovenous malformations (AVMs) of the brain stem are, fortunately, rare clinical entities. Prompt diagnosis and anatomic evaluation of patients with brain stem hemorrhages resulting from AVMs have been greatly facilitated by high resolution CT scanning and particularly MR image scanning. The goal of any treatment is complete occlusion of the malformation with minimal risk to the patient, primarily to prevent rebleeding and further neurologic injury from the AVM. PMID- 8353448 TI - Cavernous angiomas of the brain stem. AB - Cavernous angiomas in contact with the pial or ependymal surfaces of the brain stem can be totally and safely resected. Such an approach is recommended for symptomatic patients. For asymptomatic patients whose lesions are deeply embedded in the parenchyma, close observation without surgical intervention is recommended. PMID- 8353449 TI - Tumors of the medulla. AB - Intrinsic tumors of the medulla are amenable to gross total or radical subtotal resection in 30% to 50% of cases. Many of these lesions are histologically benign, and, with careful selection, aggressive surgical treatment has a role. PMID- 8353450 TI - Tumors of the pons. AB - Advances in imaging have made possible confident diagnosis of infiltrative pontine gliomas without biopsy. When the diagnosis is in doubt, stereotactic biopsy is the procedure of choice. Surgical intervention is restricted to tumors with a dorsally exophytic component and other rare circumstances. PMID- 8353451 TI - Tumors of the midbrain. AB - Focal midbrain tumors in childhood are usually low-grade astrocytomas amenable to surgical resection. Small lesions presenting only with hydrocephalus are best treated by cerebrospinal fluid diversion without biopsy or surgical resection. PMID- 8353452 TI - Infectious lesions of the brain stem. AB - Infectious lesions of the brain stem are rare and include primarily abscess and encephalitis. The most common etiologic agents for abscess formation are Streptococcus sp., Staphylococcus sp., and M. tuberculosis. Encephalitis is associated most often with L. monocytogenes and herpes simplex virus infection. Classical brain stem syndromes are uncommon with brain stem infections, and CSF obstruction can be seen with neurocysticercosis. The diagnosis of these lesions has been greatly aided by CT and MR imaging. Microsurgery and stereotaxis are both appropriate techniques for the treatment of brain stem abscess that establish a diagnosis, identify the causative agent, and relieve mass effect on important neural structures. Symptoms of hydrocephalus should be treated with temporary or permanent CSF diversion. Viral involvement of the brain stem is usually self-limited, and improved antimicrobial therapy has contributed to a decrease in the morbidity and mortality of bacterial and parasitic infections. Although once believed to be uniformly fatal, infections of the brain stem have now been successfully treated for more than a decade. PMID- 8353453 TI - Surgical treatment of syringobulbia. AB - The treatment of syringobulbia requires a precise diagnosis of the etiology. This allows a surgical procedure directed at treating the underlying etiology or decompressing the hindbrain. In most cases, symptoms can be greatly improved. PMID- 8353454 TI - Rehabilitation of the lower cranial nerves. AB - Brain stem lesions frequently cause dysfunction of the lower cranial nerves. Even with successful treatment, dysfunction may remain. Various methods for rehabilitating the patient with persistent lower cranial nerve dysfunction are presented. PMID- 8353455 TI - Management of ophthalmic complications in surgery of the brain stem. AB - This article reviews assessment and rehabilitation of abnormalities of the afferent and efferent visual system that may follow surgery of the brain stem. Attention is drawn to newer techniques of assessment (contrast sensitivities and binocular visual fields) and of management (low vision aids, Fresnel prisms, botulinum toxin injections, and adjustable suture strabismus surgery). PMID- 8353456 TI - Control of the circulation by endothelial mediators. Inaugural G.B. West Memorial Lecture. PMID- 8353457 TI - Diagnostic approaches to allergy. PMID- 8353458 TI - Identification of cockroach aeroallergens from living cultures of German or American cockroaches. AB - The Air Sentinel and polytetrafluoroethylene (PTFE) membranes were used to capture airborne particles over living colonies of German or American cockroaches. Silver-stained SDS-PAGE gels revealed protein bands at 80, 55, 36, and several bands below the 33-kD marker. SDS-PAGE/immunoblots of PTFE eluates from German cockroach colonies incubated with serum from cockroach-sensitive individuals revealed IgE-binding bands with apparent molecular weights of 36 and 80 kD. Only the 36-kD allergen and allergens below the 33-kD marker were evident in the American PTFE eluate. ELISA analysis with a monoclonal antibody assay identified the presence of both Bla g I and Bla g II in the German PTFE eluate. No Bla g I or Bla g II could be identified in the American PTFE eluate. These studies demonstrate that in addition to Bla g I and Bla g II, several other aerosolized allergens become airborne over cockroach colonies and may be important in the environment where cockroaches are abundant. PMID- 8353459 TI - Sequence polymorphisms of cDNA clones encoding the mite allergen Der p I. AB - Sequence information has been obtained from 5 cDNA clones encoding the major house dust mite allergen Der p I, including one which codes for the full length preproenzyme form of the molecule. All translated sequences were unique with 1-3 differences between each clone. 4/5 of the substitutions found were to residues found in Der f I and two positions had a substitution in more than one clone. The polymorphisms included residues already described to be in T cell epitopes, so as well as being necessary to consider them in the construction of synthetic allergens, the substitutions will be important for the interpretation of experimental and genetic studies. PMID- 8353460 TI - Isolation and preparation of antisera to ovine IgE. AB - Elevated levels of ovine reaginic antibody were induced by immunization with Ascaris suum antigens. The PCA activity of this antibody persisted in the skin of sheep for 20 days and was abolished by heating to 56 degrees C, suggesting that it was immunoglobulin E. Attempts to isolate IgE from this hyperimmune serum by gel filtration, ion exchange and affinity chromatography resulted in the preparation of a PCA-positive fraction containing proteins with molecular weights of 70, 56 and 22 kD on SDS-PAGE. This preparation was used to raise an antiserum in a rabbit to IgE which was rendered specific by absorption. An antiserum to the heavy chain of ovine IgE was also raised in a rabbit by immunization with a fraction prepared from the 68- to 80-kD region of SDS-PAGE by excision and electroelution. Both antisera were positive in reverse cutaneous anaphylaxis tests and recognized a single protein with a molecular weight of 70-72 kD on SDS PAGE immunoblotting. The presence of this protein in reaginic sheep serum, the molecular weight of its heavy chain, its heat lability and long-term skin sensitizing ability are characteristic of IgE. PMID- 8353461 TI - Augmented passive transfer of contact sensitivity in severe combined immunodeficiency mice and its dependence of V beta 8+ cells in the picryl system. AB - The passive transfer of contact sensitivity using picryl chloride immune cells from H-2 syngenic BALB/c donors was analyzed in severe combined immunodeficiency (SCID) mice which lack functional T and B lymphocytes. H-2-restricted and antigen specific contact sensitivity was transferred to SCID mice, and comparison between the level of contact sensitivity and the number of transferred cells showed a significantly more efficient transfer to SCID than to BALB/c mice. The cells passively transferring contact sensitivity were shown to carry the V beta 8 phenotype. Moreover, chromium-labeled cells from BALB/c PC1-primed donors localize normally in peripheral lymphoid organs and an increased percentage of cell arrival in the ears is clearly observed in SCID after challenge with picryl chloride. PMID- 8353462 TI - Relationship of interleukin-4 to isotypic distribution of anti-double-stranded DNA antibodies in systemic lupus erythematosus. AB - IgG subclasses of anti-double-stranded DNA antibodies were determined in 182 patients with systemic lupus erythematosus. All isotypes were detected, but IgG1 and IgG3 were predominant (62 and 51% of the cases, respectively). An average of 64 +/- 27% was IgG1, 16 +/- 22% IgG2, 16 +/- 19% IgG3 and 4 +/- 10% IgG4. The rank order or frequency was IgG1, IgG3, IgG2 and IgG4 in patients with musculoskeletal involvement; IgG1, IgG2, IgG3 and IgG4 in those with renal complications; IgG3, IgG1, IgG2 and IgG4 in those with cutaneous involvement; and IgG1, IgG3, IgG2 and IgG4 in those with hematological manifestations. Interleukin 4 (IL-4) was detectable in 17 of 36 selected patients, as opposed to 1 of 40 normal controls. The percentage of the total autoantibody contributed by IgG1 was significantly higher (p < 0.03) in these patients than in the remainder with undetectable levels of IL-4. PMID- 8353463 TI - In vitro interleukin-5 production of peripheral blood mononuclear cells is increased in patients with asthma. AB - To determine whether the capacity of interleukin-5 (IL-5) production is increased in patients with asthma, we studied in vitro IL-5 production from peripheral blood mononuclear cells (PBMC) in 27 asthmatics (16 allergic asthmatics and 11 nonallergic asthmatics) and 10 normal subjects. IL-5 production of phytohemagglutinin (PHA)-stimulated PBMC was significantly greater in asthmatics than in normal subjects (p < 0.02). IL-5 production of PBMC by IL-2 stimulation was also significantly increased in asthmatics compared with that of normal subjects (p < 0.05). In contrast, IL-2 production of PHA-stimulated PBMC did not significantly differ between asthmatics and normal subjects. In addition, the number of CD4+ and CD8+ T cells in PBMC or CD4+/CD8+ ratio did not significantly differ between asthmatics and normal subjects, whereas CD25+ T cells were significantly increased in asthmatics compared with those of normal subjects (p < 0.02). Finally, there was no significant correlation between the in vitro IL-5 production of PBMC and blood eosinophil counts in asthmatics and normal subjects. Our results indicate that the capacity of IL-5 production, but not of IL-2 production, is increased in asthmatics. The increased capacity of IL-5 production might be involved in the migration and activation of eosinophils in the airways of asthmatics. PMID- 8353464 TI - Alteration in T cell subset phenotypes as cell markers for rejection or long-term allograft acceptance in allografted rats treated with antithymocyte globulin. AB - The alterations in the absolute levels of lymphocyte phenotype subsets were measured in a rat model for heart allograft acceptance induced by antithymocyte globulin (ATG). In untreated, allografted rats all T lymphocytes decreased with 50% within 3 days after transplantation and recovered within 1 week. ATG alone induced a depletion of 75% of the T lymphocytes, which did not normalise until 60 days after treatment. During the first 10 days, ATG-treated rats with an accepted allograft had higher levels of T lymphocytes than those with rejections while the T lymphocytes recovered faster after day 10 in the later rats. The study demonstrates different alterations in T lymphocytes phenotype subsets between rejecting rats and rats with long-term accepted allograft. It also shows that the operation trauma with rejection as well as the ATG treatment strongly influence the T cell subsets. PMID- 8353465 TI - Heterogeneity in the IgE binding to a peptide derived from the house dust mite allergen Der p II indicates that the IgE response is highly polyclonal. AB - The fine specificity of IgE antibody binding to peptide 65-78 of the house dust mite major allergen Der p II was examined by comparison with binding to two peptides in which the cysteines corresponding to cys73 and cys78 in Der p II were substituted by serines and methionines. Differences in binding behavior indicated that at least three different subpopulations of IgE antibodies bound to peptide 65-78. Even at the level of such a small fragment the IgE response in individual donors proved to be polyclonal. PMID- 8353466 TI - [Cutaneous parasitism by Leishmania (Leishmania) chagasi during South American visceral leishmaniasis]. AB - Eighteen patients from the northeastern Brazilian State of Ceara with proven kala azar were studied for evidence of skin parasitism: two had ulcerative or papular skin lesions and 16 had clinically normal skin. Punch biopsies (3 mm) of intact paraspinal subscapular skin were performed on all patients; in those with papular or ulcerative lesions biopsies also were taken from an active site. One of each of the subscapsular biopsies and half of each biopsy from an active lesion were studied; the other specimens were seeded on NNN Difco Blood Agar Base Medium for parasite culture. The biopsies revealed a discrete to intense mononuclear inflammatory infiltrate, predominantly perivascular in nature. No amastigotes were observed in any tissue sections but 7 of the 18 patients yielded promastigotes on skin culture identified by monoclonal antibodies and by enzyme electrophoresis as Leishmania (Leishmania) chagasi [L. (L.) chagasi]. The isolation of Leishmania (Leishmania) chagasi, the recognized aetiologic agent of visceral leishmaniasis in the New World, from the skin of nearly 40% of 18 AVL patients proves dermatotropism of L. (L.) chagasi occurs and may be frequent in neotropical human visceral leishmaniasis (AVL.). Infected persons with skin parasites could act as a reservoir of infection and allow human to human transmission. PMID- 8353467 TI - [Epidemiological, clinical and biological features of mucocutaneous leishmaniasis in Bolivia after a 221 patient sample]. AB - The authors present a clinical, biological and epidemiological study of 221 cases of mucocutaneous leishmaniasis observed in Bolivia between January 1990 and April 1991. The patients exhibited cutaneous lesions in 136 cases and mucous involvement in 85 cases. It is stressed on the severity of the disease in Bolivia. PMID- 8353468 TI - [Parasitological efficacy of repeated treatments with ivermectin in an onchocerciasis focus in north Cameroon]. AB - 321 adults living in an hyperendemic onchocerciasis focus in North-Cameroon who received a first dose of ivermectin (150 micrograms/kg) in 1987 and a total of three, four or five doses from 1987 to 1991 were parasitologically examined in 1992. The prevalence of skin microfilariae (PMf) and the geometric mean microfilarial load (GMMf) were respectively reduced by 33 and 97% from the initial values in the group of subjects who received five treatments. In 1992, the PMf and the GMMf were not significantly different in the groups which received three, four or five doses of ivermectin. It is not necessary to achieve an important drug coverage to maintain a tolerable level of infestation in the community. PMID- 8353469 TI - [Autochthonous anguilluliasis in France]. PMID- 8353470 TI - [A case of polyradiculoneuritis associated with dengue in a patient native to French Guiana]. AB - An acute polyradiculoneuritis in a woman native of French Guiana has been observed with serologic conversion against flaviviruses by inhibition of hemagglutination test. Dengue's diagnostic was been kept in spite of lack of causal virus isolation and non-typical clinical symptoms. Association dengue polyradiculoneuritis appears quite uncommon and is worthy of note, in view of frequency of infection by Flaviviruses. PMID- 8353471 TI - [Tropical endemic limbal conjunctivitis in Cameroon patients. Apropos of 819 cases in Yaounde]. AB - The authors report the epidemiological and clinical aspects of tropical endemic limbo-conjunctivitis in 819 cameroonian patients followed up from June 1989 to June 1990: Tropical endemic limbo-conjunctivitis constitutes about 4% of causes of consultation in our services. The population concerned with LCT is composed of 46.28% of girls and 53.72% of boys; 85% of patients presenting with tropical endemic limbo conjunctivitis are aged between 7 months and 15 years; Allergy and past family history of tropical endemic limbo conjunctivitis are rare and filariasis is an aggravating factor of the disease; The pure globus form is the most frequent (80%) and we did observe especially stages I and II of the disease; The disease does not seem to cause blindness in our area. Synonym: Vernal kerato conjunctivitis. PMID- 8353472 TI - [Introduction of onchocerciasis in Central America: the role of the French expeditionary corps to Mexico (1861-1867)]. AB - Close relationships between American and African strains (from savanna) of onchocerciasis have been confirmed by biochemical analysis. It is admitted that the parasite could have been introduced by slave trade. But in Mexico, Torroela supported the hypothesis that onchocerciasis was introduced by Nubian soldiers of the French troops between 1861 and 1867. Some of the 600 soldiers of the Egyptian bataillon, included in the French expeditionnary corps, could have been onchocerciasis carriers. But these troops caserned in Vera Cruz remained in the littoral plain and have not been in contact with the Oxoaca focus of onchocerciasis. It is very unlikely that they can have been at the origin of the disease focus. PMID- 8353473 TI - [Seroprevalence of the human immunodeficiency virus (HIV) in pregnant women coming for maternity consultation to the hospital center of Libreville (Gabon) in June 1990]. AB - The pregnant women as a control group was chosen in 1990 in order to estimate the HIV Seroprevalence in Libreville. As a result of that survey it appears that the prevalence of that retrovirus seems to remain under 2% and that those women are HIV-1-infected. PMID- 8353474 TI - [Surveillance of HIV seroprevalence in Mauritania]. AB - The results of our study in four years, blood donors and tuberculosis patients HIV seroprevalence using ELISA for detection HIV1/HIV2 antibodies and Western blot for confirmation, indicate that seroprevalence in blood donors is 0.28% without a significant increase tendency. Our data show that 88 HIV seropositive confirmed, 70% were HIV1, 25% HIV2 and 5% double reactivity HIV1/HIV2. PMID- 8353475 TI - [Bacteriological aspects of purulent meningitis in Bamako district. Apropos of 1,541 bacterial strains collected from 1979 to 1991]. AB - This study is about bacteriological aspects of purulent meningitis in Bamako area upon 1,541 strains collected from 1979 to 1991. It showed that N. meningitidis, S. pneumoniae and H. influenzae b are responsible. In general, N. meningitidis is the most frequent, but this depends on years and months. Since 1988, N. meningitidis serogroup C has supplanted serogroup A. N. meningitidis is predominant between 7 to 30 years. S. pneumoniae between 1-28 days and 31 to 68 years, H. influenzae between 1 month to 6 years. The frequency of these species is the same in male and female. The 3 species are quite sensitive to antibiotics tested except sulphonamides and cotrimoxazole. Meanwhile, the appearance of strains of S. pneumoniae to penicillin and H. influenzae to ampicillin must be followed with interest to check any time the importance of the phenomenon. PMID- 8353476 TI - [Clinical, epidemiological and therapeutic aspects of purulent meningitis in the adult. Apropos of 74 cases treated at CHU of Brazzaville (Congo)]. AB - During 2 years and 9 months, 74 patients were hospitalized to purulent meningitis at the Hospital of Brazzaville and 33 were bacteriologically confirmed. The pneumococcus was responsible in 24 cases (33.4%). The analysis of 74 files showed that 34 patients died, 40 were completely cured without any after effect. The factors for these bad prognosis are: the presence of signs of cerebral pains; a CSF cytology inferior to 500 cells/mm3; total CSF proteins inferior to 2 g/l and the time before hospitalisation superior to 5 days. PMID- 8353477 TI - [Initial resistance to streptomycin, isoniazid, rifampicin and ethambutol in bacillus-laden tuberculosis patients at the National Center of Pneumo-physiology at Cotonou (Benin)]. AB - The authors are reporting results from a study about BK sensitivity among principal antituberculosis drugs in Benin Republic: 81.5% of them are susceptible for all specific antibiotics, 8.5% are offering resistance to INH and Streptomycin together. In this preliminary study no primitive resistance for RMP has been found. PMID- 8353478 TI - [Purulent pleurisy in a specialized hospital environment in Bamako]. AB - We report the results of a retrospective study of 108 cases of pleural empyema collected in the Pneumo-Phthisiology Department of the National Hospital of "Point G" from September 1984 to August 1990. The sex-ratio is 3/1 in favour of males with a mean age of 35.5 years. The pleural empyema represent 2.2% of all patients admitted in the Hospital and 20.2% of liquid effusions of the Pleura observed during the study period. The causal common germ has been placed in a proeminent position in 18 cases (16.7%) including 14 cases of gram-positive germs. Tuberculous aetiology has been proven in 16 cases (27.6%) against 67 cases of bacterial pleuresies (62%). The initial treatment has consisted in an empirical antibiotherapy of a large spectrum associated with repeated washing punctions. A short-term antituberculous chemotherapy (8 months, 2RHZS(6TH)) has been administrated each time the tuberculous aetiology has been proven or strongly presumed. The therapeutic results have been favourable in 85 cases (78.7%) and unfavourable in 23 cases (21%) including 10 deaths (9.2%). PMID- 8353479 TI - [Coprological evaluation of refugees in Strasbourg between January 1986 and December 1990]. AB - 1,000 refugees living in Strasbourg have had a stoll parasitologic exam between 1986 and 1990. We have not retained results of South America and other areas of Asia subjects because of their scarce total number. Proportionally, the most numerous are the South East Asia Nationals (51.7%); followed by those from Middle East and Africa (20 and 15.5%) and more recently by those from East of Europe (5.2%). Their parasitic infestation's rate remains important (60.9%) but variable depending on their origin. Thus, people coming from Middle East and Africa are parasited mainly by protozoan, although those from South East Asia are parasited by helminths. It's interesant to notify that the prevalence of D. fragilis is ten times higher among East European people than in the common people. PMID- 8353480 TI - [Herpes Zoster, predictive element of human immunodeficiency virus infection (HIV). Epidemio-clinical study in Cotonou (Benin)]. AB - An epidemio-clinical study of Herpes Zoster in 39 healthy patients of Benin has permitted to the authors to evaluate the positive predictive value of Herpes Zoster for HIV infection on West Africa; and to compare it with results of central Africa. The mean age of patients is 34.74 years. The positive predictive value of Herpes Zoster for HIV infection is 41.02%. It is increased by the cranial site of Herpes Zoster. PMID- 8353481 TI - A simple non-radioactive method for diagnosis of Huntington's disease. PMID- 8353482 TI - A PCR method for accurate assessment of trinucleotide repeat expansion in Huntington disease. PMID- 8353483 TI - Improved PCR conditions for the stretch of (CAG)n repeats causing Huntington's disease. PMID- 8353484 TI - Denaturing gradient gel electrophoresis (DGGE) assay for K-ras and N-ras genes: detection of K-ras point mutations in human lung tumour DNA. AB - Point mutations in the ras oncogenes are very common in lung cancers as well as in many of the other solid tumours. To effectively examine the occurrence of these mutations in a large number of tumour samples, we have applied denaturing gradient gel electrophoresis (DGGE) for the analysis of point mutations of the K ras and N-ras genes, using GC-clamped, PCR-amplified DNA fragments. Among the 68 tumour DNA samples, we detected 14 mutations in the K-ras gene. This was 78% of the mutations identified by oligonucleotide hybridization. Altogether, eight of the nine different kinds of base substitutions found in the tumour samples were detected by the DGGE assay, representing substitutions at codons 12, 13, and 61 of the K-ras gene. Six of the detected mutations were guanine to thymine transversions at codon 12; this was the most common type of alteration. On the basis of our experience, the present non-radioactive DGGE analysis seems to be readily applicable for detection of the mutations in the K-ras and N-ras genes. Types of ras gene mutations frequent in adenocarcinomas of the lung are also discussed. PMID- 8353485 TI - Mouse neurofibromatosis type 1 cDNA sequence reveals high degree of conservation of both coding and non-coding mRNA segments. AB - To identify evolutionary conserved domains and facilitate the recognition of potentially significant mutations in NF1 patients or tumors, we have determined the complete approximately 12 kb sequence of mouse neurofibromatosis type 1 mRNA. The sequence predicts a 2841 amino acid protein that is more than 98% identical to human neurofibromin. All but 9 of the 45 amino acid differences between mouse and human neurofibromin occur in the N-terminal half of the protein, with 16 changes clustered just upstream of the IRA-related segment. Given the high degree of sequence identity, virtually any sequence alteration in NF1 patients or tumors is potentially significant. We have also found that the 3' untranslated segment of NF1 mRNA is highly conserved, suggesting that this region may also be a target for mutations in NF1 patients. PMID- 8353486 TI - Fine mapping of the human SCIDX1 locus at Xq12-13.1. AB - Previous linkage analysis of families with X-linked severe combined immunodeficiency (SCIDX1) mapped this locus to a large region encompassing about 10 to 20 cM at Xq12-21. We have analyzed in SCIDX1 families the segregation of 7 highly polymorphic microsatellites repeats localized to this region, including a new polymorphic microsatellite at the DXS135 locus described in this study, to refine the mapping of this disease locus. The observations of genetic recombinants within the previously defined SCIDX1-region allow us to establish new flanking markers at the DXS135 and DXS227 loci, which significantly reduce the region harboring the SCIDX1 locus to a distance estimated between 3 to 5 cM. The existence of multiple, highly polymorphic markers in the refined SCIDX1 region will greatly improve the accuracy of carrier detection and prenatal diagnosis for SCIDX1. PMID- 8353487 TI - Evolutionary conservation of possible functional domains of the human and murine XIST genes. AB - The human XIST gene, a candidate for a role in X chromosome inactivation, has recently been cloned and sequenced, yielding a 17 kb cDNA with no apparent significant, conserved open reading frame. In addition, the XIST transcript has been localized within the nucleus to the Barr body by RNA in situ hybridization. This subnuclear localization and lack of any significant protein-coding potential suggest that XIST may act as a functional RNA within the nucleus. In the absence of a conserved open reading frame, we have turned to evolutionary studies as a first step toward elucidating a function for XIST in the process of X inactivation. While probes for XIST detect homologues in numerous eutherians, sequence comparisons require significant gapping and reveal identity levels intermediate between those seen for coding and non-coding regions in other genes. Further, sequence comparison of the most likely candidate open reading frame among several primate species reveals sequence changes not normally associated with protein-coding regions. Other features of XIST are conserved in different species, however, including the position of a major transcription start site and active X chromosome-specific DNA methylation patterns at the gene's 5' end. Finally, a possible molecular basis for differing propensity toward X inactivation between Xce alleles in mouse is investigated by comparing the sequence of the Xist conserved 5' repeats in mouse strains carrying different Xce alleles. PMID- 8353488 TI - A gene from chromosome 4p16.3 with similarity to a superfamily of transporter proteins. AB - We have previously used exon amplification to identify the ADD1 gene in cosmid Y24 from the Huntington's disease (HD) region of 4p16.3. The same technique has now yielded a second gene from this cosmid. This gene appears to encode a novel member of a superfamily of transporter proteins that includes active and passive transporters in a number of species. The predicted protein of 455 amino acids displays sequence similarity with the E. coli tetracycline resistance efflux protein encoded by cloning vector pBR322, and with a number of related transporters. This gene should open a route to isolating additional mammalian members of this growing superfamily. PMID- 8353489 TI - Intergenerational stability of the myotonic dystrophy protomutation. AB - The amplification of the CTG trinucleotide repeat in myotonic dystrophy (DM) correlates with increasingly severe phenotypes. We designate its minimal amplification the 'protomutation' since it is the mutation itself at an early stage of intergenerational evolution and is associated with very mild clinical signs. From the study of 536 DM mutation carriers (from 158 affected families), a total of 60 DM-parent/DM-offspring pairings were identified in which the parent had the protomutation. We found a strong correlation between the protomutation length and the amplification observed in the next generation. We also observed the stable transmission of the protomutation through successive generations. This stability may explain the maintenance in the population of this autosomal dominant disease despite the low reproductive fitness of severe DM phenotypes. PMID- 8353490 TI - Molecular diagnosis of homozygous myotonic dystrophy in two asymptomatic sisters. AB - The genetic defect underlying myotonic dystrophy (DM) has been identified as the expansion of an unstable trinucleotide repeat sequence, and this discovery has led to new approaches to diagnosis and genetic counselling in families with the disorder. We report the genetic analysis of a consanguineous DM family in which two asymptomatic sisters had been shown to be homozygous for the 'at risk' haplotype. PCR analysis of the region spanning the trinucleotide expansion demonstrated that both sisters possessed two alleles with repeat sizes normally seen in minimally affected patients. Extensive clinical examination failed to demonstrate any of the symptoms of DM in these women. The implications of this finding, both for understanding the disease mechanism, and for genetic counselling in such situations are discussed. PMID- 8353491 TI - Direct retroviral-mediated transfer of a dystrophin minigene into mdx mouse muscle in vivo. AB - At the cellular level, the primary pathology in Duchenne muscular dystrophy (DMD) is caused by deficiency of the sarcolemmal-associated protein, dystrophin, in the striated musculature. Here we describe the somatic transfer and long-term expression of a human dystrophin minigene corresponding to a mild Becker muscular dystrophy (BMD) phenotype in skeletal muscle tissues of the dystrophin-deficient mdx mouse by direct retroviral transduction. Following a single intramuscular injection of recombinant retrovirus, sarcolemmal expression of dystrophin was observed in an average of approximately 6% of myofibres in treated tibialis anterior muscles and was associated with activated reappearance of at least one component (43kD) of the dystrophin-glycoprotein membrane complex (DGC). Furthermore, expression of recombinant dystrophin was observed in muscle tissues up to 9 months after treatment and a significant enhancement of retrovirus mediated myofibre transduction was obtained in mdx muscle undergoing experimentally-induced regeneration. The results clearly demonstrate that retroviral transduction of activated satellite cells in regenerating skeletal muscle is a feasible route for direct and stable dystrophin gene transfer into muscle tissues in vivo. PMID- 8353492 TI - Novel alleles, hemizygosity and deletions at an Alu-repeat within the neurofibromatosis type 1 (NF1) gene. AB - Neurofibromatosis type 1 (NF1) (von Recklinghausen) is a common autosomal dominant disorder, characterised by the presence of peripheral neurofibromas, cafe-au-lait spots and Lisch nodules of the iris. Due to the high mutation rate at the NF1 locus, most patients are expected to have different mutations, limiting molecular analysis and genetic counseling to the identification of the mutation in each patient or family, or to the use of DNA polymorphisms. We have analysed an Alu-repeat polymorphic sequence (AAAT), located in intron 27 of the NF1 gene, in 70 NF1 and 40 CEPH families and we have detected several genetic and molecular abnormalities. In two families the NF1 individuals were hemizygous at the AAAT-repeat and/or at the CA-repeat of intron 27 of NF1, due to interstitial deletions, which include intron 27 to exon 37 of the NF1 gene. A 71-bp deletion at the Alu sequence was detected in non-NF1 chromosomes of members of three NF1 families. New alleles at the AAAT-repeat were found in one NF1 family and in three CEPH families giving a mutation rate for this AAAT-repeat of 0.36% per allele, which is one of the highest detected for a microsatellite locus. PMID- 8353493 TI - Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy. AB - The clinical progression of Duchenne muscular dystrophy (DMD) patients with deletions can be predicted in 93% of cases by whether the deletion maintains or disrupts the translational reading frame (frameshift hypothesis). We have identified and studied a number of patients who have deletions that do not conform to the translational frame hypothesis. The most common exception to the frameshift hypothesis is the deletion of exons 3 to 7 which disrupts the translational reading frame. We identified a Becker muscular dystrophy (BMD) patient, an intermediate, and a DMD patient with this deletion. In all three cases, dystrophin was detected and localized to the membrane. One DMD patient with an inframe deletion of exons 4-18 produced no dystrophin. One patient with a mild intermediate phenotype and a deletion of exon 45, which shifts the reading frame, produced no dystrophin. Two patients with large inframe deletions had discordant phenotypes (exons 3-41, DMD; exons 13-48, BMD), but both produced dystrophin that localized to the sarcolemma. The DMD patient, 113, indicates that dystrophin with an intact carboxy terminus can be produced in Duchenne patients at levels equivalent to some Beckers. The dystrophin analysis from these patients, together with patients reported in the literature, indicate that more than one domain can localize dystrophin to the sarcolemma. Lastly, the data shows that although most patients show correlation of clinical severity to molecular data, there are rare patients which do not conform. PMID- 8353494 TI - Refined localization and yeast artificial chromosome (YAC) contig--mapping of genes and DNA segments in the 7q21-q32 region. AB - The chromosome localizations for 159 gene and DNA segments have been refined to one of five intervals in the 7q21-132 region through hybridization analysis with a panel of somatic cell hybrid lines. Seventy-two of these chromosome 7 markers are also mapped on common or overlapping yeast artificial chromosome (YAC) clones. In addition, the breakpoints of chromosome rearrangement contained in five of the somatic cell hybrid lines have been defined by flanking probes within YAC contigs. To provide a framework for further mapping of the 7q21-q32 region, we have established the physical order of a set of reference markers: cen-(COL1A2 D7S15-CYP3A4-PON)-D7S456-(brea kpoint contained in cell hybrid 1EF2/3/K017)-GUSB D7S186-ASL-(PGY1-PGY3 -GNB2-EPO-ACHE)-D7S238-(proximal breakpoint in GM1059-Rag5) D7S240-(CUTL1-PLANH1)-(breakp oints in 1CF2/5/K016 and 2068Rag22-2)-(PRKAR2B D7S13)-LAMB1-(breakpoint in JSR-17S)-DLD-D7S16-MET-WNT2-CFTR-D7S8-tel. PMID- 8353495 TI - A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. AB - The human dopamine D4 receptor contains a novel polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of direct imperfect 48-bp repeats in the gene. Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display different pharmacological properties. Further analysis of the repeat region using innovative technologies indicates that the alleles vary not only in the number of repeats (2-8 or 10 repeat units) but also in the sequence of the repeats and the order in which they appear. In 178 unrelated chromosomes we have identified 19 different repeats in 25 different haplotypes coding for 18 different predicted amino acid sequences, making this one of the most variable functional proteins currently described. PMID- 8353496 TI - Analysis of the SRY gene in 22 sex-reversed XY females identifies four new point mutations in the conserved DNA binding domain. AB - The open reading frame of the SRY gene has been examined in a series of 22 XY females with clinically defined pure gonadal dysgenesis by direct sequencing of biotinylated PCR product bound to streptavidin coated beads. Amongst the 22 XY females examined, five (two of whom are sisters) were found to have single base changes all within the highly conserved DNA binding (or HMG box) domain. In the remaining 17 cases, the SRY gene sequence was indistinguishable from that found in normal males. In three of the XY females with point mutations, the altered amino acids occur in highly conserved positions leading to non-conservative changes (Arg to Gly at position 5, Met to Thr at position 21 and Arg to Trp at position 76). Examination of the SRY gene from the father's Y chromosome has shown that the mutations at position 5 in patient SHM60 and position 21 in patient HN31 have arisen de novo. In the case of the two sibs, both have identical mutations where a C to T transition in codon 17 has created a TAG termination signal, thus suggesting that the deceased father is likely to be a gonadal mosaic for the mutation. In the case of the mutations at positions 17 and 76, the fathers are not available for investigation and so it has not been possible to determine whether the changes are de novo. These data indicate that the majority of XY females with pure gonadal dysgenesis owe their sex-reversed phenotype to mutations in as yet uncharacterised segments of the SRY gene, or, at other loci acting early in the sex-determining pathway. PMID- 8353497 TI - YAC-assisted cloning of transcribed sequences from the human chromosome 3p21 region. AB - The region surrounding the ZNF35 zinc finger protein gene on 3p21 is of particular interest, as this region of chromosome 3 is frequently involved in rearrangements and/or deletions associated with various human tumors including lung and renal carcinoma. We have analyzed yeast artificial chromosomes (YACs), identified by PCR screening, using oligonucleotides derived from the ZNF35 gene. PFGE and Southern blot/hybridization analysis revealed that the clones cover 750 kb including the ZNF35 gene. The use of specific somatic cell hybrids have allowed us to locate the YAC contig telomeric to the D3F15S2 locus, in a region which is frequently deleted in lung carcinomas. In addition, we have developed a novel cDNA hybridization protocol allowing the isolation of transcribed sequences present in the overlapping YAC clones. Using the cDNA hybridization selection, we have isolated and characterized one transcribed sequence (D3S1362E) from the 3p21 YAC contig and the corresponding cDNA has been isolated. DNA sequencing analysis indicated that the D3S1363E cDNA codes for a putative transcription factor. Northern blot analysis indicated that the D3S1362E sequence hybridized to multiple transcripts in skeletal muscle, and weakly hybridizing transcripts of similar sizes were detected in other tissues. PMID- 8353498 TI - Exon skipping in the E-cadherin gene transcript in metastatic human gastric carcinomas. PMID- 8353499 TI - Pyruvate dehydrogenase deficiency caused by a 5 base pair duplication in the E1 alpha subunit. PMID- 8353500 TI - Autosomal dominant 'sector' retinitis pigmentosa due to a point mutation predicting an Asn-15-Ser substitution of rhodopsin. PMID- 8353501 TI - Molecular defect in a patient with pyridoxine-responsive homocystinuria. PMID- 8353502 TI - Six dinucleotide microsatellite polymorphisms on human chromosome 3. PMID- 8353503 TI - Three tetrameric repeat polymorphisms on human chromosome 3: D3S1349; D3S1350; D3S1351. PMID- 8353504 TI - Unusual length polymorphism in human steroid 5 alpha-reductase type 2 gene (SRD5A2). PMID- 8353505 TI - Dinucleotide repeat polymorphism near the RP3 locus in Xp21 (DXS1110). PMID- 8353506 TI - A dinucleotide repeat polymorphism (D9S202) in the Friedreich's ataxia region on chromosome 9q13-q21.1. PMID- 8353507 TI - Dinucleotide repeat polymorphism at the human olfactory marker protein (OMP) locus on chromosome 11q13.5 near tyrosinase (TYR). PMID- 8353508 TI - Dinucleotide repeat polymorphism at the D9S126 locus (9p21). PMID- 8353509 TI - Simple sequence repeat polymorphism in the cartilage matrix protein (CRTM) gene at 1p35. PMID- 8353510 TI - D11S971 CATT polymorphism (RC27) located near the MEN1 locus at 11q13. PMID- 8353511 TI - Dinucleotide repeat polymorphism at the locus for human ferrochelatase (FECH). PMID- 8353512 TI - Dinucleotide repeat polymorphism at the human pituitary adenylate cyclase activating polypeptide (PACAP) gene. PMID- 8353513 TI - A polymorphic dinucleotide repeat at the D8S339 locus. PMID- 8353514 TI - Dinucleotide repeat polymorphism proximal to the spinal muscular atrophy region at the D5S524 locus. PMID- 8353515 TI - Trinucleotide repeat polymorphism at the D5S373 locus. PMID- 8353516 TI - New human DNA polymorphisms submitted to the genome data base. PMID- 8353517 TI - Aldehyde dehydrogenase (ALDH) activity in Drosophila melanogaster adults: evidence for cytosolic localization. AB - The subcellular localization of the aldehyde dehydrogenase activity from the ALDH (EC 1.2.1.3) enzyme has been studied in nutritionally manipulated Drosophila melanogaster adults from a wild (LRC) and an ADH-null (bAdhn4) strain. ALDH activities from ALDH or ADH (EC 1.1.1.1) enzymes were selectively inhibited by prefeeding respectively the flies sucrose solutions supplemented with either cyanamide or acetone respectively. ALDH, ADH (as a cytosolic marker) and succinate dehydrogenase (EC 1.3.9.1) (as a mitochondrial marker) activities were assayed in both the mitochondrial and cytosolic fractions isolated from flies subjected to each treatment. Total ALDH activity in the cytosolic fraction was found to be between five (ADH strain) and ten (ADH strain) times higher than that in the mitochondrial fraction. Prefeeding cyanamide resulted in a 64% (ADH strain) and a 90% (ADH strain) reduction of the cytosolic ALDH activity, whereas prefeeding acetone resulted in a 38% (ADH strain) reduction of this activity. Prefeeding both cyanamide and acetone resulted in a total inhibition of ALDH activity, which was also observed after an extended cyanamide treatment. In conclusion, our results support that, contrary to what occurs in larvae, in adults the ALDH activity from ALDH enzyme is mainly localized in the cytosolic fraction: about 85% in ADH+ and 90% in ADH- strains. Although larvae and adults use different ALDH activities to detoxify acetaldehyde (from ADH and ALDH enzymes, respectively) both of them are cytosolic. Reasons for these different uses are discussed in relation to the subcellular localization of ALDH activity. PMID- 8353518 TI - Drosophila suzukii contains a peptide homologous to the Drosophila melanogaster sex-peptide and functional in both species. AB - A peptide homologous to the Drosophila melanogaster sex-peptide (SP) was isolated from Drosophila suzukii accessory glands and its amino acid sequence determined. The D. suzukii peptide contains 41 amino acids and has a calculated molecular weight of 5100 Da. Comparison of the sequences reveals strong homologies in the N terminal and C-terminal parts of the peptides. In the D. suzukii sex-peptide, however, five additional amino acids are inserted after amino acid 7. Based on the sequence of the peptide, a cDNA coding for the D. suzukii peptide was isolated by PCR. Sequence analysis of the cDNA confirmed the SP amino acid sequence determined by peptide sequencing. Furthermore, based on the cDNA sequence, we isolated the D. suzukii sex-peptide gene by inverse PCR. The D. suzukii sex-peptide gene contains an intron and codes for a 60 amino acid precursor. The D. melanogaster and the D. suzuki sex-peptides elicit rejection behaviour in the presence of males and an increased egg laying in virgin females of both species. PMID- 8353519 TI - Purification and primary structure of ceratotoxin A and B, two antibacterial peptides from the female reproductive accessory glands of the medfly Ceratitis capitata (Insecta:Diptera). AB - In the present article we report the purification and the amino acid sequence of two antibacterial peptides present in the secretion of the female reproductive accessory glands of the dipteran insect Ceratitis capitata. Both peptides consist of 29 amino acid residues, are heat stable, strongly basic and differ from each other for the substitution of two amino acids. Their primary sequence and predicted secondary structure are related to other families of peptides known to have lytic and/or antibacterial activity. We propose the name ceratotoxins (from Ceratitis) for these antibacterial peptides. PMID- 8353520 TI - Purification and properties of the soluble midgut trehalase from the gypsy moth, Lymantria dispar. AB - The midgut trehalase (THA) from fifth instar Lymantria dispar (gypsy moth) larvae was purified to homogeneity by two separate methods: gel filtration followed by Rotofor preparative IEF, and affinity chromatography on trehalose coupled to Sepharose 6B followed by preparative polyacrylamide gel electrophoresis. Midgut THA from the last stadium L. dispar larvae existed mainly in soluble form and displayed a single band of activity in nondenaturing polyacrylamide gels when stained by a THA-specific staining procedure. Analytical IEF of purified midgut THA revealed a single protein band with an apparent pI of 4.6. SDS-PAGE and gel permeation studies indicated that the smallest active form of THA in the late fifth instar larval midgut was a monomeric protein with an approximate size of 60 kDa. A specific activity of 67 units/mg of protein at 30 degrees C and at pH 6.4 was determined for the enzyme purified by affinity chromatography and preparative gel electrophoresis. The midgut enzyme exhibited a very high substrate specificity with a Km of 0.4 mM for trehalose. The enzyme was maximally active at pH 5.4-6.0 and was thermally stable at temperatures up to 65 degrees C. The midgut THA was insensitive to inhibition by a high concentration of Tris, sucrose, p-nitrophenyl-beta-D-glucoside or phloridzin. Divalent cations metal ions, hypertrehalosaemic hormone and octopamine had no significant effect on the activity of the purified enzyme in vitro. The purified enzyme was inactivated by modification with DEP and was competitively inhibited by castanospermine with an apparent Ki of 0.8 x 10(-6)M at pH 6.4. PMID- 8353521 TI - A cuticle-degrading proteinase from the moulting fluid of the tobacco hornworm, Manduca sexta. AB - Moulting fluid of pharate adult tobacco hornworm moths, Manduca sexta, contains a novel cuticle-degrading proteinase, designated as MFP-1. The enzyme has been purified using heparin affinity chromatography and partially characterized. Before purification MFP-1 is associated with a large complex having an apparent native molecular mass > 669 kDa. After purification MFP-1 has a molecular mass of 41 kDa. The pI of the enzyme is 5.54. MFP-1 can be classified as generally trypsin-like on the basis of its substrate specificity and inhibition by soybean trypsin inhibitor. The enzyme's preferred substrate, Tos-Gly-Pro-Arg-pNA, its inhibition by hirudin, and its affinity for heparin, all indicate that MFP-1 has some characteristics in common with the vertebrate blood-clotting enzyme thrombin. MFP-1 is probably a serine protease, since it is inhibited by both DFP and PMSF (specific inhibitors of serine proteinases). However, the enzyme was also inhibited by a number of agents that affect cysteine proteinases. Purified MFP-1 degrades Manduca cuticle in vitro. We suggest that the enzyme may act as the first step in the degradation of the cuticle during the moulting process. PMID- 8353522 TI - Effects of parasitism by the braconid wasp Cotesia congregata on host hemolymph proteins of the tobacco hornworm, Manduca sexta. AB - Parasitism by the braconid wasp Cotesia congregata causes major alterations in the hemolymph proteins of host tobacco hornworm larvae. Earlier studies showed that the total amount of hemolymph protein is reduced during parasitism, beginning almost immediately after the host is parasitized. Simultaneously, parasitism induces synthesis of large amounts of novel proteins that appear in the blood as early as 1-2 h post-parasitization. The present report confirms earlier studies describing the presence of novel proteins in last instar hosts, and also characterizes the effects of parasitism in altering the titers of several endogenous host hemolymph proteins normally produced by the fat body and other tissues. Analysis of hemolymph plasma using SDS-PAGE and densitometry, as well as immunodiffusion assays, showed that in terminal stage fifth instar host larvae, the titers of serpins and arylphorin were dramatically reduced relative to the levels of these proteins detected in nonparasitized gate II fifth instar larvae of the same age. The relative differences between parasitized and nonparasitized larvae increased with time following ecdysis to the fifth instar, so that the day 4 nonparasitized larvae had arylphorin titers of c. 30 mg/ml, whereas parasitized day 4 larvae with newly emerged wasps had only one sixth that amount of storage protein circulating in the hemolymph. Similarly, in nonparasitized larvae the hemolymph serpin concentration increased from c. 200 micrograms/ml (on day 0) to > 600 micrograms/ml (on day 4) in prewandering gate II larvae, but in parasitized larvae the hemolymph serpin concentration was maintained in the range of 100-200 micrograms per ml hemolymph until the pharate third instar parasites emerged from the host larva on day 4. In contrast, the level of hemolymph lipophorin was unaffected by parasitism, and lipophorin increased from c. 1.3 to > 3 mg/ml during the time interval between days 0 and 4 in both nonparasitized and parasitized larvae. Hemolymph titers of insecticyanin also were not significantly different in parasitized vs nonparasitized larvae, and in both types of larvae the concentration of this pigment decreased by c. 50% during the same time interval when lipophorin was increased significantly. Instead of causing a generalized inhibition of host hemolymph protein synthesis, parasitism causes a complex array of changes in the hemolymph protein profile of Manduca sexta, possibly via the mediation of hormonal modulators of host protein synthesis, or transcriptional or translational regulation of host gene expression by factors associated with the polydnavirus or molecules secreted by the parasites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8353523 TI - Purification and characterization of a trypsin-like digestive enzyme from spruce budworm (Choristoneura fumiferana) responsible for the activation of delta endotoxin from Bacillus thuringiensis. AB - A trypsin-like enzyme purified from spruce budworm (Choristoneura fumiferana) gut juice has a molecular mass of 25 kDa and its pH activity profile indicates a pKa of 8. Sequence homology with bovine trypsin of the N-terminus and active site, and the ionization dependence for catalysis, reflect the typical trypsin-like activities measured. The action of this enzyme (designated CFT-1) is compared to the neat gut juice with regard to the proteolytic activation of the delta endotoxin from Bacillus thuringiensis. PMID- 8353524 TI - Sequence of a 17 kDa vacuolar H(+)-ATPase proteolipid subunit from insect midgut and Malpighian tubules. AB - A 0.4 kb polymerase chain reaction (PCR) product obtained from cDNA made from the midgut and Malpighian tubules of fifth instar larvae of Heliothis virescens was used to screen a larval midgut and Malpighian tubules cDNA library. Four clones were obtained, one of 1.9 kb and others of 1.4 kb. The 1.9 kb clone encodes a 17.2 kDa protein which is highly homologous to other vacuolar ATPases proteolipids. Putative N-glycosylation and DCCD binding sites were observed at amino acid residues 83 and 139, respectively. PMID- 8353525 TI - Sequence of a cDNA and expression of the gene encoding epidermal and gut chitinases of Manduca sexta. AB - Insects use chitinolytic enzymes to digest chitin in the exoskeleton during the molting process. We have isolated and sequenced a chitinase-encoding cDNA from the tobacco hornworm, Manduca sexta, compared its sequence with genes encoding chitinolytic enzymes from other sources, and studied chitinase gene expression and hormonal regulation during the larval-pupal transformation. The insert DNA in this clone is 2452 nucleotides long with an open reading frame of 1662 nucleotides that encodes a protein of 554 amino acids with a molecular weight of 62 kDa. Several regions of the amino acid sequence in this protein are similar to sequences in yeast, cucumber and bacterial endo-beta-N-acetylglucosaminidases. Hybrid-selection of mRNA and in vitro translation yielded an immunoreactive protein with an apparent molecular mass of 75 kDa, which is similar to the size of a chitinase present in pharate pupal molting fluid. Southern blot analysis indicated that one or two genes related to the cDNA clone are encoding chitinases in the Manduca genome. The major tissues expressing chitinase genes were the epidermis and gut with mRNA levels highest on c. days 5-7 during the fifth larval instar. Injection of 20-hydroxyecdysone into ligated fifth instar abdomens caused about a 10-fold increase in mRNA levels in both epidermis and gut, and topical application of the juvenile hormone mimic, fenoxycarb, suppressed the ecdysteroid induced accumulation of chitinase RNA. PMID- 8353526 TI - Mass spectrometry and characterization of Aedes aegypti trypsin modulating oostatic factor (TMOF) and its analogs. AB - Trypsin modulating oostatic factor (TMOF), a decapeptide that directly inhibits the biosynthesis of trypsin- and chymotrypsin-like enzymes in epithelial cells of mosquito midgut and indirectly inhibits vitellogenesis in anautogenous females, has been sequenced by Fourier transform mass spectrometry analysis. The peptide has a primary amino acid sequence of NH2-Tyr-Asp-Pro-Ala-(Pro)6-COOH and probably exhibits left-handed helical conformation as was shown by computer stereoview simulation. The factor is metabolized very rapidly (half-life of 1.6 h) in intact mosquitoes when injected after the blood meal. Inhibition of trypsin biosynthesis was followed in ligated abdomens, which synthesize trypsin but do not metabolise TMOF. At concentrations of 3 x 10(-9) M and 6.8 x 10(-6) M, TMOF inhibited 50 and 90% of trypsin-like enzyme biosynthesis, respectively. Several analogs of varying chain lengths were synthesized and evaluated for biological activity using dose response curves. Switching the positions of Tyr and Asp at the N-terminus reduced the activity of the hormone, indicating that the N-terminus is important for biological activity. Removal of two to five prolines at the C-terminus also reduced activity, indicating that both the N- and C-termini are important. Synthesis of trypsin-like isozyme was followed in several insect species using [1,3-3H]diisopropyl-fluorophosphate (DFP) in the presence of tosylamide-2 phenylethyl chloromethyl ketone. Marked reduction of [1,3-3H]diisopropyl phosphoryl-trypsin-like derivatives was noted after TMOF treatment, as assessed by polyacrylamide gel electrophoresis. These results indicate that the biosynthesis of trypsin-like enzyme in mosquitoes and other insects may be regulated by sequence-related TMOFs. PMID- 8353527 TI - Identification and quantification of juvenile hormone biosynthesized by larval and adult Australian sheep blowfly Lucilia cuprina (Diptera: Calliphoridae). AB - Recent evidence indicates that higher dipterans biosynthesize predominantly the novel juvenile hormone (JH) bisepoxide, methyl (2E,6trans)-6,7,10,11-bisepoxy 3,7,11-trimethyl-2-dodecen oate (JHB3), together with a small proportion of methyl (2E,6E)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate (JHIII) and possibly its 6,7-epoxy isomer. A strategy of gas chromatography-mass spectrometry (GC-MS) involving cool on-column GC and negative-ion chemical ionization MS has enabled the selective analysis of underivatized JH-like products released in vitro by ring glands and corpora allata of Lucilia cuprina. JHB3 is released to the exclusion of mono-epoxidized and unepoxidized esters. The rate of JHB3 release in adult females increases dramatically after protein feeding from 0.2 to 5.2 pmol/h/gland. Values agree well with the rate of JH biosynthesis determined by radiochemical assay. As revealed by thin-layer chromatography, the radiolabel is predominantly incorporated into JHB3, of which only 2% is retained in the corpus allatum indicating almost immediate release from the gland. Approximately 5% of radioactive material retained in the glands co-migrates with JHIII and may be an intermediate in JHB3 synthesis. We conclude that JHB3 is the only juvenile hormone biosynthesized in vitro by L. cuprina. The data suggest that JHB3 may be the exclusive JH synthesized by higher dipterans. PMID- 8353528 TI - Tissue distribution of microsomal cytochrome P-450 monooxygenases and their inducibility by phenobarbital in the insecticide resistant LPR strain of house fly, Musca domestica L. AB - Cytochrome P-450s, cytochrome b5, P-450 reductase, and four P-450 monooxygenase activities were abundant in proximal intestine (PI), Malpighian tubules (MT), and fat bodies (FB) in the insecticide resistant (LPR) strain of house fly. Insecticide resistance in LPR flies was associated with increases in P-450 monooxygenase activities in nearly all of these tissues relative to an insecticide susceptible strain. Cytochrome P-450lpr was present in all tissues and at higher levels in LPR than in susceptible flies suggesting that the role of P-450lpr in monooxygenase-mediated insecticide resistance is not due to its higher levels in a single tissue. However, it appears that fat bodies may have a major role in resistance due to their relatively large size and the abundance of P-450lpr in this tissue. Total cytochrome P-450s, cytochrome P-450lpr and P-450 monooxygenase activities were generally refractory to phenobarbital (PB) induction in LPR. This contrasts with a previous report in susceptible house flies showing that P-450 monooxygenases were induced by PB. It appears that total P-450s, cytochrome P-450lpr and monooxygenase activities were expressed at constitutive high levels in several tissues of LPR house flies. PMID- 8353529 TI - Dietary ethanol stimulates the activity of phosphatidylcholine-specific phospholipase D and the formation of phosphatidylethanol in Drosophila melanogaster larvae. AB - When administered in the diet to third instar Drosophila melanogaster larvae, short chain primary alcohols reduce phosphatidylcholine (PC) levels. The ethanol induced reductions in larval PC may be in part due to an increase in the activity of PC-specific phospholipase D (PC-specific PLD, EC 3.1.4.4). PC-specific PLD not only hydrolyzes PC, but it also apparently catalyzes the formation of phosphatidylethanol. PC-specific PLD activity was also stimulated by 200 mM ethanol, methanol, isopropanol, n-butanol, and n-propanol. In vitro studies indicated that Drosophila PC-specific PLD activities were enhanced by submicromolar concentrations of Ca2+ and by GTP-gamma S. In vivo studies utilizing [14C]lyso-palmitoyl phosphatidylcholine indicated that dietary ethanol promoted the flux of label into triacylglycerol, 1,2 diacylglycerol, and fatty acid ethyl esters, while the label in PC decreased. PMID- 8353530 TI - [Proceedings of the 88th annual meeting of the American Urological Association (AUA). San Antonio, 15-20 May 1993]. PMID- 8353531 TI - Transgenesis in chickens. AB - The application of transgenic technology to domestic poultry offers an alternative means to conventional practice for improvement of this highly productive agricultural species. The hen's reproductive system has unique characteristics which have imposed limitations on the use of established methods for artificial gene transfer. In this article, we review the various strategies that have been adopted to overcome the problem. Target sites for gene insertion include the fertilized ovum, the blastodermal embryo in the unincubated egg, and the primordial germ cells. Notable success in obtaining somatic and germline transformation has been achieved with the use of retroviral vectors to infect the blastodermal embryo. Current attempts to introduce DNA directly into the genome, without resort to pathogen-derived vectors, are discussed. PMID- 8353532 TI - Sexing and detection of gene construct in microinjected bovine blastocysts using the polymerase chain reaction. AB - We present a polymerase chain reaction (PCR)-based procedure for rapid bovine embryo sexing and classifying embryos for the presence of exogenous DNA. Fourteen bovine blastocysts microinjected with gene construct DNA at the pronuclear stage were divided into quarters and subjected to amplification with construct-specific and sex gene-specific (ZFY/ZFX) primers in the same initial PCR reaction. Blastocysts carrying microinjected construct DNA could be identified by the presence of construct-specific PCR product in approximately 4 h. Approximately half of the microinjected and two of 16 non-microinjected blastocysts typed PCR positive for the construct DNA. Owing to erroneous amplifications in the two non microinjected control blastocysts, and the inability of the system to distinguish integrated from non-integrated copies of the microinjected construct, the number of construct-positive blastocysts determined in our assay most likely overestimates the number of true transgenic embryos. Nevertheless, using this assay, we were able to determine that approximately half of the microinjected embryos were negative for the transgene construct and thus could be eliminated from transfer to a recipient cow. Embryo sexing was achieved in less than 6 h by restriction fragment length polymorphism analysis of nested ZFY/ZFX PCR products reamplified from initial PCR reactions. In 11/14 microinjected blastocysts all sections assayed unambiguously as the same sex. In one embryo, only one section was analysed, while two other blastocysts showed some discrepancies of sexing results between the sections analysed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353533 TI - The endosperm-specific expression of a rice prolamin chimaeric gene in transgenic tobacco plants. AB - The 5' upstream region (-680 to +40), containing the potential promoter and complete signal peptide coding sequence of the rice seed storage prolamin gene was amplified in vitro using the polymerase chain reaction from the genome of Chinese rice cultivar Zhonghua 8. The physical map and DNA sequence analysis show strong homology with the 5' flanking region of the rice prolamin gene published by Kim and Okita (1988a). No change in the signal peptide coding sequence and a long leader sequence with several small open reading frames were found. The chimaeric gene containing the 5' flanking region of the prolamin gene (-680 to 18) was transcriptionally fused with the beta-glucuronidase (GUS) reporter gene and the fusion junction was confirmed by both physical mapping and DNA sequence analysis. The resultant chimaeric gene was used to transform tobacco explants, using the Ti binary system of Agrobacterium tumefaciens LBA4404. Three transgenic tobacco plants with as many as 20 copies of the chimaeric GUS gene (confirmed by dot and Southern hybridization) were analysed further. Histochemical analysis revealed GUS activity in the endosperm tissue of tobacco seed at the developmental stage about 20 days after flowering (DAF). No GUS activity was found in leaves, stems, roots and flowers of the transgenic tobacco plants. Therefore, we conclude that the 5' upstream region from -680 to -18 was sufficient to confer the endosperm-specific expression of the rice prolamin gene. PMID- 8353535 TI - Insect-resistant chrysanthemum calluses by introduction of a Bacillus thuringiensis crystal protein gene. AB - A 3'-end truncated crystal protein gene, derived from Bacillus thuringiensis (Bt) subsp. aizawai 7.21, encoding the toxic fragment of the insecticidal protein cryIA(b), was constructed. The gene was inserted into a transformation vector, also carrying the neomycin phosphotransferase II (nptII) gene and the beta glucuronidase (gus) gene, and introduced in the oncogenic Agrobacterium tumefaciens strain A281, harbouring the Ti-plasmid pTiBO542. The recombinant Agrobacterium strain was used to transform leaf explants of chrysanthemum (Dendranthema grandiflora) cultivar Parliament. The resulting tumours were kanamycin-resistant, exhibited beta-glucuronidase activity and produced agropine and mannopine. In most tumours, all simultaneously transferred genes were expressed, owing to selection for the presence of both T-DNAs, but no correlation was found between the level of expression of the various genes. A bioassay was developed, in which larvae were fed with tumorous chrysanthemum tissue, in order to detect the effect of the transferred toxin gene on larval development. Using this bioassay with second instar larvae of Heliothis virescens (tobacco budworm), 17 tumour lines were tested. Several of these lines proved to be strongly inhibitory to larval growth. These results indicate that Bt-based insect resistance might be used as a tool in reducing the amount of pesticides used in chrysanthemum culture. PMID- 8353534 TI - Regulation of expression of transgenes in developing fish. AB - The transcriptional regulatory elements of the beta-actin gene of carp (Cyprinus carpio) have been examined in zebrafish and goldfish harbouring transgenes. The high sequence conservation of the putative regulatory elements in the beta-actin genes of animals suggested that their function would be conserved, so that transgenic constructs with the same transcriptional control elements would promote similar levels of transgene expression in different species of transgenic animals. To test this assumption, we analysed the temporal expression of a reporter gene under the control of transcriptional control sequences from the carp beta-actin gene in zebrafish (Brachydanio rerio) and goldfish (Carrasius auratus). Our results indicated that, contrary to expectations, combinations of different transcriptional control elements affected the level, duration, and onset of gene expression differently in developing zebrafish and goldfish. The major differences in expression of beta-actin/CAT (chloramphenicol acetyltransferase) constructs in zebrafish and goldfish were: (1) overall expression was almost 100-fold higher in goldfish than in zebrafish embryos, (2) the first intron had an enhancing effect on gene expression in zebrafish but not in goldfish, and (3) the serum-responsive/CArG-containing regulatory element in the proximal promoter was not always required for maximal CAT activity in goldfish, but was required in zebrafish. These results suggest that in the zebrafish, but not in the goldfish, there may be interactions between motifs in the proximal promoter and the first intron which appear to be required for maximal enhancement of transcription. PMID- 8353536 TI - [Echographic aspects of gynecomastia]. AB - Gynecomastia is a size increase of man's breast, due to non neoplastic ductal and glandular stroma proliferation. Prevalent ductal proliferation defines the "florid" type, while prevalent stroma increase defines the "quiescent" type. Pseudo-gynecomastia is a non glandular volume increase. Sonography is able to recognize the different parts of normal male breast and to diagnose gynecomastia. Moreover by sonography we can distinguish three echo-patterns linked to the anatomopathologic pattern which can lead therapy. PMID- 8353537 TI - [The role of echography in the diagnosis of adrenal masses]. AB - Ultrasound investigations, which are non-invasive and have a relatively low cost, are of primary importance nowadays in the diagnosis of a number of abdominal diseases. Nevertheless, their use to study adrenal masses still gives rise to different interpretations, as the small dimensions, deep position within the retroperitoneum and fatty envelopment of the normal adrenal gland make it difficult to identify using this method. However, the introduction of new equipment and probes with a higher image resolution, combined with increasing experience on the part of the operators, is greatly improving the situation. The percentage of visualization of the normal adrenal gland, which in the past was only 78% on the left and 44% on the right, according to Yeh, now oscillates between 90 and 95% on the left and 70 and 90% on the right. The overall sensitivity of ultrasound investigations found by the A.A. on a total of 44 expanding processes successively subjected to surgery, was 86.3% (96% on the right, 68.4% on the left, with a sensitivity of 100% for all masses greater than 3 cm. These results confirm the role of ultrasound in the diagnosis of adrenal masses. PMID- 8353538 TI - [Cystic renal pathology]. AB - Ultrasonography has a great interest in diagnosis of cystic kidney disorders for typical eco-pattern of this pathology. In this work we show the eco-pattern of the most common cystic kidney disorders. Particularly we examine simple cysts (typical, atypical, complicated), multicystic kidney dysplasia, autosomal recessive polycystic kidney disease (infantile) autosomal dominant polycystic kidney disease (adult age). The so-called neoplastic cysts (multiloculated cysts, multiloculated cysts nephroma, cystic nephroblastoma), medullar cysts (medullary sponge kidney, medullary cystic disease), parapyelic cysts, acquired cystic kidney disease in renal failure patients, parasitic cysts, epidermoid cysts. About this disorders we present the more typical and expressive ultrasonographic appearance and we define the role and the opportunity of diagnostic setting by echography, moreover ultrasonography allows us to make a differential diagnosis between cystic kidney disorders and other kidney disease. PMID- 8353539 TI - [Uronephrologic echography: state of the art]. AB - We report the ultrasound usefulness and capacity of them to be explain several disease that find field of uronephrology. We value the improvement make to the system. At the time, in fact, it is the early diagnostic technique to be performed. The AA emphasize the absence of invasiveness, the simplicity and the good compliance. Ultrasonography limit the application of more invasive and complicate procedure as TAC and RM. PMID- 8353540 TI - [Echo-guided puncture of intraprostatic cysts]. AB - The occurrence of an obstruction of the ejaculatory ducts, in spite of its rarity, must be considered by the Urologists in the screening of the etiologic causes of obstructive azoospermia. Nowadays, the diagnostic approach, which includes the biochemical study of seminal plasma and prostatic ultrasound, often leads to the preoperative recognition of the site of obstruction. Various surgical and endoscopic techniques have been adopted for the treatment of ejaculatory duct obstructions in different historical periods. Herein we describe our experience that starts from 1979. 17 infertile patients with intraprostatic cysts and 2 with a stenosis of the veru montanum were treated by us following these criteria: 9 azoospermic patients underwent scrototomy and endoscopy; 10 patients with a severe oligozoospermia underwent echo-guided puncture of an intraprostatic cyst. The patients were placed in the lithotomy position, a 16 G needle was adopted and by means ultrasound was possible to follow the needle entering the cyst. When no spermatozoa was detected in the cystic liquid, sclerosing agents (Sodium-tetradecyl-sulphate 30 mg in 1 l.) was introduced. This easy procedure was carried out on outpatients in local anaesthesia. One out of ten oligozoospermic patients had to repeat the echo-guided puncture of intraprostatic cyst as the first attempt had been followed by recurrence. Eight out of ten subfertile patients who had undergone percutaneous echo-guided treatment had longer than 1 year follow-up: in seven cases an increase in sperms number and motility was obtained; in one case sperm count remained unmodified. In three cases the partners became pregnant. PMID- 8353541 TI - [Echo-flowmetric control 6 years after percutaneous treatment of varicocele]. AB - Several Authors have discussed the long term efficacy of sclerotherapy; somebody supposes that percutaneous angiographic treatment of spermatic vein is not sure at all because the occlusion due to the sclerosing agents is not retained as long lasting. Studies have been done by other Authors about comparison of recurrent varicocele anatomy following surgery and percutaneous balloon occlusion: it is concluded that venous collaterals are identified easily by renal venography, and knowledge of these collaterals is helpful in planning further radiological treatment. Since 1980 we have always treated left varicocele by means of percutaneous sclerotherapy of the spermatic veins following renal phlebography: the treatment is done on an outpatient basis, in local anaesthesia. Sclerosing agents we usually adopt are: sodium-tetradecyl sulphate and alcohol. At our knowledge long-term results of this treatment have never been published; this is the reason for which long-term follow-up of 27 patients that 6 years ago underwent percutaneous sclerotherapy was done. Only 16 of them have accepted to repeat: a) physical examination; b) Doppler flowmetry; c) scrotal ultrasound. The presence of a varicocele was demonstrated in 2 out of 16 patients (12.5% of the case). These data confirms that percutaneous treatment performed following the procedures we adopted in 1986 has a long term efficacy in 87.5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353542 TI - [Echo-guided transperineal and transrectal prostatic biopsy: complications of the 2 methods]. AB - We evaluated the complications of transrectal and transperineal ultrasound-guided prostatic biopsy in 280 patients. All patients underwent antibiotic prophylaxis with a different scheme according to the approach for the biopsy. Urine culture and, in some patients, blood culture have been collected after biopsy. We have reported the same rate of complications for the two modalities except for a lower rate of positive urine culture and blood culture in the group of patients submitted to transperineal biopsy; this type of approach, then, should be considered of first choice in some patients with a higher risk of infections. PMID- 8353543 TI - [A case of congenital renal malformation with arteriovenous fistula]. AB - Renal arteriovenous fistulas caused by vascular malformation are relatively rare, with a reported prevalence of less than 0.04%. The authors discuss about a clinical case studied by Echo-color-doppler, C.T. scan and Digital angiography. Nevertheless there is a good correlation between the results from these different Imaging Techniques, Duplex-Doppler seems to be poorly specific to define by itself a diagnosis of a tumoral renal mass. PMID- 8353544 TI - [Color Doppler echography of the cavernous bodies after F.I.C. in the study of erectile impotence of vascular origin]. AB - Study with the Doppler method has been associated with "cavernometrics" and "cavernography" in erection pathologies for some time. But this enquiry is burdened not only be technical inaccuracies such as the lack of knowledge of the angle of incidence of the doppler wave and the diameter of the explored vessel etc, but also by intrinsic difficulty method itself. Therefore, the authors have used a color Doppler to individuate and study the cavernous arteries, and present the results obtained from a group of 21 patients, all affected by erectile deficits, who were selected on the basis of anamnestica and clinical criteria. They individualized 21 patients in whom the vasculogenic nature of their affection appeared probable, out of the 125 who were under their observation for their sexual inadequacy. In three patients the clinical suspicion of a venous incompetency was confirmed by dynamic "cavernometrics with cavernography". The study of the four phases of erection (flaccidity, tumescence, erection, detumescence) was carried out after an intracavernous injection of 20 micrograms of PGE/1. The parameters considered were: systolic velocity of the hematic wave, diastolic speed, the index of resistance and range. In cases of vasculogenic impotence with an arterial base the systolic wave in the 2nd and 3rd phases presented a speed inferior to the norm of standard values, the resistance index altered by the lacking of physiological increment due in the erectile beyond the closing of venous "polsters", also to the rigidity of the albuginea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353545 TI - [Transrectal echography in the diagnosis of cervico-urethral obstruction in the young]. AB - The authors present a case of severe cervico-urethral obstruction by Von Brunn cysts. These cysts are often found even in macroscopically healthy bladders, but only rarely reach such a size as to be revealed by ultrasound. They can be asymptomatic or cause obstruction if large. They are no longer considered preneoplastic lesions and are therefore treated according to symptoms. When these cysts cause dysuria they are removed, preferably by transurethral resection, as it is the only method (unlike needle aspiration) which prevents recurrence. PMID- 8353546 TI - [Echographic evaluation of kidney transplant "en bloc"]. AB - Kidney transplants from infant donors are associated in the literature with poor results as regards both functionality and the survival of the transplant. Hence the increasing frequency, for kidneys obtained from donors under 5 years of age, of a surgical technique defined as "en bloc", involving the transplant of both kidneys into a single receiver and using the donor aorta and vena cava for vascular anastomosis. This technique seems to provide results comparable with those obtained using adult organs. Ultrasound and Doppler investigations are routinely performed in patients undergoing such a transplant. This study presents ultrasound and Doppler images of "en bloc" transplants, with particular reference to one case of pseudoaneurysm of the donor aorta and one of stenosis of the renal artery, revealed by Echo-Color-Doppler. The importance of ultrasound in this kind of transplant is emphasized, as it enables post-operative monitoring of the physiological growth in volume of the two transplanted infant kidneys. PMID- 8353547 TI - [Transrectal echography in the evaluation of the effects of endocavitary laser therapy in patients with bacterial prostatitis]. AB - 104 patients with acute bacterial prostatitis were randomized to an antibiotic therapy group (group I) and an antibiotic plus laser therapy group (group II). Laser therapy was applied ever other day through a trans-rectally inserted fiberoptic probe. Resolution of the symptoms occurred in 87% of the patients in group I and 92% in group II (p < 0.001). Transrectal ultrasound resulted in resolution of the peri-prostatic venous plexus congestion in 43.7% of the patients in group I and 89.7% in group II. In conclusion, the combination of laser therapy and antibiotics in bacterial prostatitis provides both a better resolution of the symptoms and a reduction or disappearance of the peri-prostatic venous congestion. PMID- 8353548 TI - [Echography in the follow-up of patients receiving an endoscopic injection of teflon for vesico-renal reflux]. AB - The surgical treatment of vesicorenal reflux implies open surgery and consequently an hospitalization. The sub-ureteric injection of poly-tetra-fluoro ethylene (Teflon) for correction of vesicorenal reflux was first utilized in 1981 by Matouschek. We have reviewed our personal experience with endoscopic correction of vesicorenal reflux from 1985 to 1990 and evaluated the importance of ultrasonography especially in the follow up. PMID- 8353549 TI - [Echo-guided puncture of intraprostatic cysts: our experience]. AB - Prostatic cysts are a pathological condition which is rare and still poorly known. In the past a precise diagnosis was difficult and was made with radiologic examination and/or cystoscopy and/or surgery. Up to date echotomography is the most important technique not only for the diagnosis but also for the treatment of prostatic cysts. The Authors relate upon their experience about diagnosis and treatment of prostatic cysts. PMID- 8353550 TI - [Echographic localization and monitoring of bladder calculi treated with ESWL]. AB - The standard treatments for bladder stones consist either of an open operation or endoscopic transurethral disintegration and extraction. These treatment require anesthesia and hospitalization. We report our experience of ESWL monotherapy in the treatment of 10 patients affected by bladder stones. Our early datas show that ESWL for bladder stones is a safe an effective therapy which can be performed without the use of anesthesia in an outpatient basis. PMID- 8353551 TI - [Echo-Doppler evaluation of the renal arterial flow in hepatic cirrhosis]. AB - In liver cirrhosis the sodium retention depends on a decreased renal perfusion by arteriolar vasoconstriction. To evaluate the usefulness of echo-Doppler in detecting such hemodynamic impairment, we studied 16 cirrhotic patients and 16 healthy subjects as control group. We measured Pulsatility Index (P.I.) and Resistivity Index (R.I.). Both parameters resulted to be statistically higher in cirrhotic patients than in controls; moreover they resulted to be higher in cirrhotics with ascites than in those without. Therefore echo-Doppler can detect intraparenchymal renal vasoconstriction in cirrhosis, this impaired perfusion is already evident before ascites formation. PMID- 8353552 TI - [The role of echography in the evaluation of stenosis of the male urethra]. AB - Twenty male patients with known urethral stricture disease were evaluated using Ultrasonic urethrography, retrograde and anterograde urethrography and Cystoscopy for comparative analysis of the three techniques. The Ultrasonic urethrography provides the most accurate information regarding anatomic side, stricture length, number, the degree of scarring spongiofibrosis. Therefore the Authors suggest a larger use of this technique. PMID- 8353553 TI - [The role of echography in cancer of the penis]. AB - The Authors, observing two cases of penile cancer, lay stress on the role of Ultrasonography in this disease. Its easy and quick execution, its low cost, the possibility to repeat it, its diagnostic sensibility in evaluating the extent of the penile cancer, permit us to consider it a screening technique of primary importance. PMID- 8353554 TI - [Intracavitary echography with a 12.5 MHz microprobe: a new study method in the pathology of the urinary tract]. AB - Endoluminal sonography performed with 12.5 MHz miniature transducer-containing catheters with diameter of 6 or 9 Fr., is a new technique for the study of urinary tract. We studied: U.S. scan of 10 corpes and 10 operatory specimens (bladders and kidneys) with anatomic measurement in vitro. U.S. scan of 20 patients "in vivo" with pathologies involving bladder and upper urinary tract. We studied the normal anatomy of bladder and ureter by U.S. and we detected the structures beyond the ureteral lumen as: vessels, lymph nodes, muscle. Our indications for the utility of this new U.S. technique are: Detection and staging of superficial T.C.C. of the bladder. Detection of dangerous vessels near the U.P.F before endopielotomy. Excretory tract minus (endoluminal ultrasound is helpful in differentiating such pelvic filling defects as blood clots, no opaque stones and transitional cell carcinoma). PMID- 8353555 TI - [Echo-guided percutaneous drainage of renal cysts]. AB - Treatment of renal cysts in the ultrasound guided percutaneous drainage, associated with intra-cavital sclerosis-inducing agents to avoid recurrence, is often proposed. This report describes the technique and the most suitable sclerosis inducing agents. The best results are obtained with alcohol. No increase in complications or discomfort was observed. PMID- 8353556 TI - [Echography during drug-induced erections in the study of penile plastic induration]. AB - Clinical investigation is still fundamental in the diagnosis of La Peyronie's disease. In this study 36 patients underwent clinical investigation and ultrasound in basal conditions and during drug-induced erection, and the results were compared. In basal condition US does not provide much useful supplementary informations. During drug-induced erection US accurately visualizes plaque site and dimensions and anatomical abnormalities about corpora cavernosa, albuginea, septum and dorsal vessels. PMID- 8353557 TI - [Vesico-intestinal fistula in Crohn disease: the role of echography in its diagnosis]. AB - Ultrasound is in widespread use in the study of gastrointestinal pathologies. In Crohn disease it is helpful in diagnosing complications such as thickening of the bowel loop walls, abscesses, lymph node enlargement and vesical-enteric fistulas. This report presents two cases in which vesical-enteric fistulas were visualized by US; confirming a diagnosis of Crohn's disease in one case, and diagnosing the fistula during the follow-up in the second patient in whom Crohn's disease had previously been diagnosed. PMID- 8353558 TI - [Traumatic injuries of the urethra: an echographic study]. AB - US in the lower urinary tract usually explores the bladder and the prostatic urethra. In this study we used US instead of x-rays to visualize the remaining urethra in 42 patients. US was useful in the presence of urethral trauma. The site and extent of injury, particularly peri-urethral lesions (hematomas, urinary collection and abscesses in relation to the urethra) were observed. Ultrasound's efficacy and reproducibility were also useful in post-operative follow-ups. PMID- 8353559 TI - Should government further regulate physician supply? Yes. PMID- 8353560 TI - Should the government further regulate physician supply? No. PMID- 8353561 TI - Dynamic pay initiatives. AB - In the battle to manage change and deal successfully with health care reform, hospitals are looking to innovative methods to optimize compensation for their executives. Results of the 1993 Hay Hospital Compensation Survey indicate clearly that the pressures of managed care and the uncertainty--but inevitability--of reform are forcing organizations to use new tools and strategies for achieving productivity and quality goals. Another interesting survey finding: Two positions critical to the success of integrated health care systems--the head of medical affairs and the head of managed care--show significant compensation growth during the past two years. PMID- 8353562 TI - A call for consultants. AB - There is a consensus that reform will create a boon for consultants. Many organizations have already brought in consultants to help formulate new strategies; but how do you find the right one? PMID- 8353563 TI - Biotech on the brink. PMID- 8353564 TI - Managing costs and care. Medicare bundled pricing CABG demo is catching on fast. AB - After two years of experimenting, hospitals and physicians participating in the Medicare bundled-payment CABG project are enthusiastic. Their effort may offer a model for future collaboration. PMID- 8353565 TI - Seniors speak up. Advocates for the elderly prepare for congressional reform debate. AB - Senior citizen advocacy groups are preparing for the release of the Clinton administration's reform plan. And policymakers are expected to listen when they speak up. PMID- 8353566 TI - Sizing up Pennsylvania. Geisinger aims to reshape its delivery system. PMID- 8353567 TI - Joseph A. Califano Jr. A former HEW secretary looks at health care reform. Interview by Terese Hudson. AB - Joseph A. Califano Jr. was secretary of Health, Education and Welfare in the Carter administration and is now president of the Center on Addiction and Substance Abuse at Columbia University, an independent not-for-profit research center. He also serves as an adjunct professor of public health at Columbia University. Califano has written eight books, including America's Health Care Revolution: Who Lives? Who Dies? Who Pays?, published in 1986. He will speak at the American Society for Healthcare Marketing and Public Relations 15th annual meeting, Sept. 11-14 in San Francisco. He spoke recently with Senior Editor Terese Hudson about the possibilities and problems in the current move to reform health care. PMID- 8353568 TI - Mind/body medicine makes an impression on San Diego. PMID- 8353569 TI - Telecommunicators making their way into the health care market. PMID- 8353570 TI - Data watch. Americans speak out on health care reform. PMID- 8353571 TI - Breaking down assumptions, managing change. PMID- 8353572 TI - Creating change in the ICU: the battle with tradition, tenure and tenacity. PMID- 8353573 TI - Cardiopulmonary support in the intensive care unit. PMID- 8353574 TI - Myocardial contusion: new concepts in diagnosis and management. AB - Myocardial contusion is diagnosed with one or a combination of four diagnostic procedures: electrocardiography, echocardiography, creatine kinase MB fractions and/or radionuclide procedures. This article presents a critical review of 18 recent studies addressing the utility, sensitivity and specificity of these tests. Careful review suggests that clinically significant myocardial contusions as a result of blunt trauma are rare and may be detected simply and inexpensively using electrocardiography and careful physical examination. Serum myocardial enzymes and radionuclide studies are nonspecific and are not predictive of cardiac complications. Echocardiography is useful in the management of myocardial decompensation but not as a primary screening tool in blunt cardiac injury. Cost comparisons, resource allocation and implications for critical care practice are discussed. PMID- 8353575 TI - Evaluation of the effects of heparinized and nonheparinized flush solutions on the patency of arterial pressure monitoring lines: the AACN Thunder Project. By the American Association of Critical-Care Nurses. AB - OBJECTIVE: To evaluate the effects of heparinized and nonheparinized flush solutions on the patency of arterial pressure monitoring lines. SAMPLE: A total of 5139 patients from 198 participating sites comprised the sample for this large scale, randomized clinical trial. METHODS: Patients were randomly assigned to heparinized and nonheparinized flush solution treatment groups. Data were collected at 4-hour intervals for up to 72 hours on presence of acceptable square waveform and arterial backflow. RESULTS: Arterial pressure monitoring lines maintained with heparinized flush solutions had a significantly greater probability of remaining patent over time than lines maintained with nonheparinized flush solutions. In addition to heparin, four other variables significantly influenced the probability of lines remaining patent: receiving other anticoagulants or thrombolytics, having a catheter longer than 2 inches, femoral insertion site and male gender. CONCLUSIONS: Chances for patency are greatest in men with long femoral lines who receive other anticoagulants or thrombolytics and heparinized flush solutions. Risks of nonpatency are greatest in women with short nonfemoral lines who do not receive other anticoagulants or thrombolytics and have nonheparinized flush solutions. PMID- 8353576 TI - Is stress at hospital discharge after acute myocardial infarction greater in women than in men? AB - BACKGROUND: Stress surrounding hospital discharge after acute myocardial infarction increases the likelihood that the condition will recur. Although increased age, a more severe illness and a higher incidence of persistent cardiac symptoms suggest that women would experience more stress at discharge, data comparing stress experienced by women and men have not been reported. PURPOSE: To compare the level of stress experienced by women and men at hospital discharge after acute myocardial infarction. SAMPLE: Data from 54 women and 182 men from a government hospital, two private community hospitals and a teaching/community hospital. RESULTS: Stress scores of women were not found to be different from those of men, nor were five of the six most stressful concerns identified in the study. No difference was found in severity of illness or age. CONCLUSIONS: Women and men experience similar levels of stress at hospital discharge after acute myocardial infarction. Furthermore, both genders can benefit equally from interventions designed to reduce stress. PMID- 8353577 TI - Clinical management of supraventricular tachycardia with adenosine. AB - Adenosine is a reliable agent to convert supraventricular tachycardia to regular sinus rhythm with few complications. Also, adenosine may be useful in the diagnosis of narrow and wide QRS complex tachycardias. Original research articles published predominantly in the last 10 years were reviewed. These articles examined the therapeutic and electrophysiologic effects of adenosine compounds and compared their actions to other antiarrhythmics. PMID- 8353578 TI - Unstable angina associated with critical proximal left anterior descending coronary artery stenosis. AB - A critical proximal left anterior descending coronary artery stenosis associated with unstable angina places a patient at extreme risk for extensive anterolateral myocardial damage with potentially irreversible hemodynamic demise. Characteristics of this pathology are a clinical profile of new-onset unstable angina, normal or minimally elevated cardiac enzymes, and 12-lead electrocardiographic indicators specific for anterolateral ischemia usually seen in periods when the patient is pain-free. Knowledge of this profile, administration and evaluation of pharmacologic therapies and a unique bedside monitoring strategy with hourly surveillance of the precordial leads are key measures necessary to stabilize and preserve the integrity of myocardial tissue until aggressive, invasive revascularization therapies are instituted. PMID- 8353579 TI - A protocol for initiation of nasal positive pressure ventilation. AB - BACKGROUND: Respiratory failure related to neuromuscular weakness has commonly been managed with long-term ventilation by tracheostomy. Currently, nasal positive pressure ventilation is being used with success in this patient population. It has been suggested that initiation of nasal positive pressure ventilation is best done in an intensive care setting. METHOD: Nine patients were placed on nasal ventilation during a brief admission to a medical floor staffed by nurses trained in respiratory care. This process was facilitated by use of a standardized protocol for nursing staff that identified treatment objectives. RESULTS: Following the initiation of nasal positive pressure ventilation, this group of patients experienced near normalization of daytime measurements of partial pressure of arterial carbon dioxide, reported increases in daytime energy levels, and relief of nighttime signs and symptoms. These objectives were accomplished with no significant complications. Use of this protocol may also decrease length and cost of hospitalization and improve patient acceptance of noninvasive ventilatory assistance. PMID- 8353580 TI - Morphine sulfate, transdermal fentanyl citrate and ketorolac tromethamine: effects on postoperative pulmonary function. AB - The physiological effects of morphine sulfate and fentanyl citrate on postoperative pulmonary function demonstrate varying degrees of respiratory depression related to dose, route of administration and pre-existing pathologies. Current postoperative analgesic therapies that include concomitant use of narcotic agonists and nonsteroidal anti-inflammatory drugs require adjustment of drug dosages to provide adequate pain relief while avoiding drug-induced complications. Specific nursing considerations include understanding therapeutic and adverse effects of these agents on pain and ventilation, continuous pain assessment and early recognition and treatment of respiratory depression. PMID- 8353581 TI - Adult respiratory distress syndrome: a consideration with rapid respiratory decompensation in association with preeclampsia. AB - Adult respiratory distress syndrome, presenting as rapid respiratory decompensation in the setting of preeclampsia at 36 weeks of gestation, was managed by early hemodynamic monitoring with pulmonary artery catheterization. With confirmation of the diagnosis of preeclampsia the patient was delivered promptly; improvement of her respiratory failure was observed within 48 hours. Consideration of adult respiratory distress syndrome in the setting of preeclampsia is discussed, with emphasis on early confirmation of the diagnosis and determination of the precise mechanisms of pulmonary edema. PMID- 8353582 TI - Effects of neck position on intracranial pressure. AB - OBJECTIVE: To investigate the effects of four nonneutral neck positions on intracranial pressure. DESIGN: An alternating treatment design was used to investigate the effect on intracranial pressure of rotation of the head to the left and right, neck flexion and neck extension. Each experimental position was separated by a neutral recovery period. SETTING: Neurological intensive care units in two tertiary care centers in the southwestern United States. SUBJECTS: Ten patients whose intracranial pressure was being therapeutically monitored but who were not experiencing prolonged periods of elevated intracranial pressure. PROCEDURE: Each neck position was maintained manually by the research staff for 5 minutes. Intracranial pressure was recorded at 1-minute intervals throughout the 45-minute data collection period. RESULTS: Rotating the head to the right and left and placing the neck in flexion resulted in significantly higher intracranial pressure readings than the baseline neutral neck position or positioning the neck in extension. The highest individual intracranial pressures always occurred with the head and neck rotated or in flexion. CONCLUSIONS: These data support previous studies that indicated that a patient at risk for pathological increase in intracranial pressure should not be positioned with the neck in flexion or the head turned to either side. PMID- 8353583 TI - Echocardiographic determination of valid zero reference levels in supine and lateral positions. AB - BACKGROUND: The phlebostatic axis--the junction of the fourth intercostal space and the midpoint of the anterior-posterior diameter--has been accepted as a reliable external reference point for the mid-right and mid-left atrium. Acceptance of this reference point is based upon research conducted in 1945 that measured venous pressures in the hands of subjects positioned with the head of the bed raised to different levels. The validity of this reference point for intracardiac pressure measurements in supine or laterally positioned patients has not been established. PURPOSE: To determine the validity of the phlebostatic axis in the supine and lateral positions. METHODS: To determine validity in the supine position, we compared the distance from the phlebostatic axis to a fixed external point (the bed surface) and the distance from the right and left atria in the supine position to this same fixed external point. The distances from the right and left atria to the bed surface were determined with echocardiography and were used as the standard for the proper position of external reference points. To determine the validity of the phlebostatic axis in lateral positions, we compared the distances from the right atrium and left atrium to the bed surface in the supine position with those distances in different lateral positions. RESULTS: We analyzed the data of 25 normal, healthy subjects. The study findings show that the phlebostatic axis is a valid reference point for the right atrium, and the phlebostatic axis and midanterior-posterior diameter are valid reference points for the left atrium in the supine position. However, neither is a valid external reference point in the lateral positions. Pressure measurements obtained when patients are in the lateral positions are not accurate. There remains a need to develop valid methods of accurate pressure measurements in various body positions. PMID- 8353584 TI - Clinical safety and cost of heparin titration using bedside activated clotting time. AB - OBJECTIVE: To evaluate the clinical safety of heparin titration and the procedural cost of anticoagulation measurement using bedside low-range activated clotting time. DESIGN: Quasi-experimental study using data gathered through retrospective record review. SETTING: Coronary care, medical intensive care and telemetry units of a community hospital. SUBJECTS: Sample of 102 patients undergoing elective percutaneous transluminal coronary angioplasty. INTERVENTION: Intravenous heparin therapy was titrated using low-range activated clotting time in 51 percutaneous transluminal coronary angioplasty patients. Data from this group were compared to a matched sample of 51 angioplasty patients whose intravenous heparin therapy was titrated using activated partial thromboplastin time. RESULTS: No differences in procedural, early or late complications were found between the groups. The cost of managing heparin therapy with low-range activated clotting time was less than with activated partial thromboplastin time. CONCLUSION: These results suggest that titrating heparin therapy based on bedside low-range activated clotting time for the angioplasty patients in this sample was as safe as with activated partial thromboplastin time. Use of bedside low-range activated clotting time saved money for the hospital. PMID- 8353585 TI - Accuracy of drawing coagulation samples from heparinized arterial lines. AB - OBJECTIVE: To determine the accuracy of activated partial thromboplastin time and prothrombin time studies when samples are drawn through heparinized arterial lines. METHODS: A total sample of 90 grouped blood samples (from 30 subjects) was used. Patients were all male, with a mean age of 65 and were studied within 24 hours of percutaneous transluminal coronary angioplasty. Each patient had three venous control and arterial line sample sets (a total of 90 blood samples) drawn when routinely ordered for monitoring therapy. For the arterial line sample, a discard volume of the deadspace, deadspace + 2 mL, or deadspace + 4 mL was randomly assigned for each sample. The venous control volumes were the same for all three sample sets. RESULTS: A 2 x 3 repeated measures analysis of variance was used to analyze the results. The independent variables were the source of the sample (venous vs arterial) and the discard volume of arterial blood (deadspace, deadspace + 2 mL, deadspace + 4 mL). The dependent variables were the activated partial thromboplastin time and prothrombin time values. Mean arterial activated partial thromboplastin time values were significantly higher than the corresponding venous values. Mean activated partial thromboplastin time values were not significantly different among the discard volumes of blood drawn. However, there was a significant source by volume interaction. Tukey post-hoc comparisons of venous-arterial activated partial thromboplastin time differences among the three volumes showed significant differences between deadspace volume and deadspace + 2 mL, and deadspace volume and deadspace + 4 mL. There was no significant difference between deadspace + 2 mL and deadspace + 4 mL volumes. CONCLUSION: Results indicated that the minimal amount of discard volume for accurate activated partial thromboplastin time values in this population of percutaneous transluminal coronary angioplasty patients was the catheter deadspace volume plus 2 mL (total 3.6 mL). PMID- 8353586 TI - Pacemaker update. Part II: Atrioventricular synchronous and rate-modulated pacemakers. PMID- 8353587 TI - An open door policy in ICU. PMID- 8353588 TI - An open door policy in ICU. PMID- 8353589 TI - Cytosolic calcium oscillators: critical discussion and stochastic modelling. AB - In the last few years, an immense amount of experimental data on agonist-induced cytosolic Ca2+ oscillations has emphasized the necessity of theoretical models accounting for these phenomena. In the first part of the paper, a critical analysis of different minimal Ca2+ oscillator models is presented, which reveals that not all of the so far proposed mechanisms are capable to reproduce experimental data adequately. The second part of the paper is devoted to a computational method using a stochastic simulation algorithm which describes the time evolution of Ca2+ oscillations at the molecular level. In contrast to the deterministic formulation of the models presented so far, the stochastic treatment takes account of the inherent fluctuations of cytosolic Ca2+ in cellular subcompartments. In the macroscopic limit, the stochastic models display dynamics analogous to the deterministic ones. PMID- 8353590 TI - Opposite effect of superoxide dismutase, L-arginine analogues, methylene blue and desferal: suppression of histamine-induced and stimulation of serotonin-induced paw edema in mice. AB - Endogenous nitric oxide (NO, endothelium-derived relaxing factor) was stimulatory for histamine- and suppressive for serotonin-induced paw edema of mice. This action was mediated by guanosine 3',5'-cyclic monophosphate production. Local injection of superoxide dismutase (SOD), catalase, NG-monomethyl-L-arginine (L NMMA), methylene blue and Desferal (iron chelator) mixed with mediator suppressed histamine-induced edema at doses between 0.1 and 100 micrograms/kg and showed no or little stimulatory effect at higher doses. L-arginine reversed the effect of L NMMA. Serotonin edema was enhanced by a high dose of these drugs. Their effect became suppressive as the histamine ratio was increased in edema induced by a histamine-serotonin mixture. This suggested that serotonin-induced vascular permeability decreased with a greater production of either O2- or NO. Cimetidine (H2-antagonist) was not effective in histamine edema of normal mice, but became suppressive (ED50 = 70 micrograms/kg) when 10 mg/kg L-NMMA was coinjected. SOD and methylene blue also rendered this edema sensitive to cimetidine. A simultaneous decrease in sensitivity to mepyramine (H1-antagonist) indicated that NO and oxyradicals kept H1-receptors activated. L-NMMA had no effect on bradykinin edema, but suppressed thrombin-, acetylcholine-, platelet-activating factor-, substance P- and FeCl3-induced paw edemata. Nitroprusside (NO donator) suppressed serotonin edema. N-Acetylcysteine and cytochrome c, but not ascorbate and hydroxyl radical scavengers suppressed histamine edema. PMID- 8353591 TI - Simultaneous, continuous, on-line and real-time spectral analysis of multiple physiologic signals by a personal-computer-based algorithm. AB - We presented in this communication a computer algorithm that offers the advantage of simultaneous analysis of the power spectrum of multiple physiologic signals, including systemic arterial pressure, single-neuronal and electroencephalographic signals, on a continuous, on-line and real-time basis. It provided sensitive definition, discrimination and quantification (graphic and digital) of the various frequency components in the spectrum. There was also great flexibility in selecting the physiologic signal(s) to be analyzed, the choice of results of analysis to be displayed for each physiologic parameter and the alteration of sensitivity and baseline of each event channel. Furthermore, it included window options to improve the frequency or temporal resolution and discrimination of the spectral changes. Most importantly, all these desirable features can be accomplished economically with a general purpose personal computer. PMID- 8353592 TI - In vitro transformation of epithelial cells by ras oncogenes. AB - Genes of the ras family of dominant transforming genes are frequently activated by specific point mutations in common human epithelial malignancies and also in many experimental tumour models. Testing of the hypothesis that ras activation is a critical event in tumorigenesis involves reconstruction of genetic events in vitro using appropriate epithelial models. This article reviews experimental transformation of human and rodent epithelial cells by ras oncogenes in vitro, alone and in combination with cooperating oncogenic events. PMID- 8353593 TI - Basal cell adhesion to a culture substratum controls the polarized spatial organization of human epidermal keratinocytes into proliferating basal and terminally differentiating suprabasal populations. AB - The contribution of adhesion to an extracellular matrix in the polarized spatial organization of keratinocytes was studied in dispase-detached cultures stored as floating sheets. Proliferating and terminally differentiating cell populations were, therefore, localized on tissue sections by their DNA-synthesizing ability and involucrin immunostaining, respectively. A progressive reorganization was induced from superposed proliferating and differentiating layers into clusters exhibiting differentiating cells on the outside. Measurements of proliferation and terminal differentiation in detached cultures revealed the progressive disappearance of proliferating cells, followed by an increase in involucrin positive cells. Attempts to block the spatial reorganization by the addition of components of the extracellular matrix remained unsuccessful. These results suggest that basal anchorage is responsible for the superposition of proliferating and differentiating cells in keratinocyte cultures. They afford new arguments for the induction of terminal differentiation in non-adhesive keratinocytes which exhibit a concomitant modification of cell shape. PMID- 8353594 TI - A defined collagen substrate and nutrient diffusion gradient culture system allows human colon cancer cells to assume a more differentiated phenotype. AB - A culture system is presented in which a biologically more relevant substrate in the form of a collagen membrane and a biologically more relevant diffusion gradient system for nutrient delivery to the cells are provided. Five established human colon cancer cell lines (Caco-2, DLD-1, Widr, HCT 116 and HCT 8) were cultured in this system and three of them showed increased differentiation compared with the same cells cultured on the usual cell culture substrates of plastic and glass and with cells grown in an anchorage-independent manner. Caco-2 cells grow on plastic as a monolayer of large pleomorphic cells with scant mucin production. When cultured in a gradient diffusion system in a sandwich of type I/IV collagen the Caco-2 cells showed the highest degree of morphological and biochemical differentiation as evidenced by cellular alignment, glandular formation and mucin production. Similarly DLD-1 cells exhibited the greatest degree of morphological and biochemical differentiation in a gradient system in a type I/IV collagen sandwich. HCT 116 and HCT 8 cells, however, showed little change in differentiation phenotype under any of the 11 culture conditions tested. Widr cells grew in a type I/IV collagen sandwich in a gradient diffusion system as multilayered sheets of cells with intercellular spaces, suggestive of a moderate increase in differentiation phenotype. As judged by morphology and mucin production a range of differentiation capacities is exhibited by the five cell lines tested under the optimal differentiating culture conditions, with the order from most able to differentiate to least able to differentiate being Caco-2 > or = DLD-1 > or = Widr > HCT 116 > or = HCT 8. PMID- 8353595 TI - Permissive and instructive induction of adult rodent prostatic epithelium by heterotypic urogenital sinus mesenchyme. AB - Adult rodent (rat and mouse) prostatic ducts (PR) were recombined heterospecifically with fetal urogenital sinus mesenchyme (UGM) (mouse UGM plus rat PR or rat UGM plus mouse PR), and the resultant tissue recombinants were grafted under the renal capsule of male athymic mice. For recombination with mouse UGM the ductal tips of each of the 4 rat prostatic lobes [ventral (VP), lateral type 1 (L1), lateral type 2 (L2), and dorsal prostate (DP)] were used. For recombination with rat UGM the ductal tips of each of the 2 mouse prostatic lobes [ventral (VP) and dorso-lateral prostate (DLP)] were used. After 1 month of growth in vivo, the DNA content of UGM+PR recombinants increased substantially (6.1- to 76.8-fold increase) over the combined DNA content of the isolated UGM and PR prior to grafting. Immunocytochemical, polyacrylamide gel electrophoretic and Western blot analyses demonstrated that irrespective of the initial source of the adult prostatic duct, the epithelium of UGM + PR recombinants continued to express its normal lobe-specific secretory proteins as well as secretory proteins specific to other prostatic lobes. For example, rat ventral and lateral type 2 prostate do not normally express DP-1, a rat dorsal-prostatic-specific protein, but after recombination with mouse UGM the induced prostatic epithelium expressed DP-1 as well as C3, a rat ventral-prostatic-specific protein. Sensitive reverse transcriptase-polymerase chain reaction techniques (RT-PCR) verified the expression of mRNA for C3 and DP-1 in such tissue recombinants. Analogous results were obtained for UGM + PR tissue recombinants constructed with prostatic ductal tips from rat L1, L2 and DP and mouse VP and DLP. These findings demonstrate that adult rodent prostatic epithelium retains a responsiveness to its connective tissue environment, and that fetal UGM can permissively induce prostatic ductal growth and morphogenesis while instructively inducing the expression of a new spectrum of prostatic secretory proteins. PMID- 8353596 TI - The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium. AB - The morphogenesis and functional differentiation of mammary epithelium depends on signalling from systemic hormones and on cues from the local tissue microenvironment. With regard to the latter, regulatory cues are mainly provided by two subcompartments of the mesenchyme/stroma [fibroblastic and adipocyte] and the subjacent basement membrane. During embryogenesis, fibroblastic mesenchyme determines the sexual phenotype of the gland while adipocyte mesenchyme controls mammary-specific ductal morphogenesis. In the juvenile animal, adipocyte stroma continues to support ductal expansion while fibroblasts negatively regulate ductal outgrowth via interactions with the epithelium possibly involving TGF-beta mediated deposition of collagen I and chondroitin sulphate. In the adult, evidence from culture studies show that the signals required for the induction of tissue-specific differentiation during pregnancy and maintenance of function during lactation arise primarily from basement membrane. Beta-casein synthesis is induced in single mammary epithelial cells embedded within a basement membrane matrix via an integrin-dependent pathway. Further support for a critical role for basement membrane in the functional differentiation of the gland comes from studies in involution where degradative loss of basement membranes correlates with loss of functional activity in the epithelium. Thus the extracellular matrix in conjunction with certain cytokines plays a central role in coordinating mammary epithelial development. The findings discussed give further credence to a modal where mammary epithelium, together with certain elements of the subjacent microenvironment, form a dynamic and reciprocally interactive functional unit that regulates tissue specific gene expression in the mammary gland. PMID- 8353597 TI - Hippocampal circuitry complicates analysis of long-term potentiation in mossy fiber synapses. AB - Much of the current interest in the hippocampus concerns a rapid and persistent form of synaptic plasticity, called long-term potentiation (LTP), that is a candidate substrate for some of the mnemonic functions of this structure. There are at least two kinds of LTP in the hippocampus. One form is found at the synapse between the mossy fibers of the granule cells and the pyramidal neurons of the CA3 region. Attempts to examine the mechanism underlying this form of LTP have yielded contradictory conclusions. The authors show how the complex circuitry of the dentate gyrus and adjacent hippocampus may have caused the contradictions. To overcome problems introduced by the circuitry, a specific set of procedures and criteria for evoking and identifying mossy fiber responses is proposed. Use of these or similar procedures and criteria will improve the design and interpretation of experiments on mossy fiber LTP and allow more informative comparisons among species and brain regions and across laboratories. PMID- 8353598 TI - Spatial learning and the saturation of long-term potentiation. PMID- 8353599 TI - Hippocampal synaptic enhancement and spatial learning in the Morris swim task. AB - The authors attempted to replicate the study of Castro, Silbert, McNaughton, and Barnes (1989) in which it was concluded that bilateral saturation of hippocampal synaptic enhancement produced a deficit in acquisition of a spatial navigation problem in the Morris swim task. The original protocol was followed as closely as possible, but no effect of long-term enhancement (LTE) saturation on spatial performance in this task was found. This negative result suggests either that the previous finding using the swim task reflected statistical error or that some as yet undetermined variable is of critical importance in this phenomenon. The present negative finding also raises a question concerning the reproducibility of the earlier results of McNaughton, Barnes, Rao, Baldwin, and Rasmussen (1986) in which LTE saturation apparently led to a prolonged deficit on a different spatial task. Although negative results in such experiments do not constitute grounds for rejecting the underlying hypothesis, the present lack of a positive effect renders uncertain, for the time being, one of the lines of experimental support for the theory that LTE at hippocampal synapses reflects a mechanism for the associative, distributed storage of new spatial information. PMID- 8353600 TI - Cumulative long-term potentiation in the rat dentate gyrus correlates with, but does not modify, performance in the water maze. AB - The electrically induced increase in hippocampal synaptic strength known as long term potentiation (LTP) is thought to involve some of the same mechanisms as those mediating information storage during spatial learning. Physiological saturation of synaptic weights might therefore be expected to occlude spatial learning. In support of this, Castro et al. (Castro CA, Silbert LH, McNaughton BL, Barnes CA, 1989, Nature 342:545-548) reported that repeated induction of LTP to asymptotic levels, over a 14-day period, blocked the ability of rats to learn the position of a hidden platform in a water maze shortly afterwards. The authors have attempted to replicate this finding in two experiments. In Experiment 1, rats were given either 400 Hz stimulation as 50 trains/day over a 5-day period, to induce LTP, or were given the same number of stimulus pulses at 1 Hz. Two hours after the last stimulation session they underwent eight spatial learning trials, occurring at 2-hour intervals. In Experiment 2, the procedure of Castro et al. was followed exactly, with LTP induced by 10 trains of 400 Hz stimulation daily for 14 days. Spatial learning trials began 10 minutes after the last stimulation session and consisted of 12 trials with alternating 30-second and 2 minute intervals. In neither experiment was a significant impairment of spatial learning observed. However, there was a strong positive correlation, in both experiments, between the final level of LTP and subsequent performance in the water maze. PMID- 8353601 TI - Induction of long-term potentiation at perforant path dentate synapses does not affect place learning or memory. AB - In two experiments the authors failed to detect an effect of inducing bilateral, long-lasting synaptic potentiation at perforant path dentate synapses on spatial learning by rats in the Morris place navigation task. Daily sessions of high frequency stimulation of perforant path axons produced large increases to an asymptotic level in population spike and field excitatory postsynaptic potential recorded in ipsilateral dentate gyrus. Place learning proceeded normally 24 hours after the last of 14 high-frequency stimulation sessions in rats that had previously mastered the procedural aspects of place navigation (Experiment 1) and in rats that were naive (Experiment 2). PMID- 8353602 TI - Differential effects of kindling and kindled seizures on place learning in the Morris water maze. AB - There is some controversy about the role of long-term potentiation (LTP) in spatial learning. The authors have found that triggering generalized kindled seizures with stimulation of the perforant path disrupts spatial learning in the Morris water maze but that kindling per se does not affect spatial learning. It is suggested that abnormal electrical activity induced by high-frequency stimulation of the perforant path may have been responsible for the disruption of spatial learning previously attributed to LTP saturation. PMID- 8353603 TI - An examination of the relations between hippocampal long-term potentiation, kindling, afterdischarge, and place learning in the water maze. AB - Two approaches were used to study the relations between the acquisition of place learning in the Morris water maze and long-term potentiation (LTP), kindling, and afterdischarge (AD). In the first, the possibility of behavioral LTP in the dentate gyrus field potential evoked by stimulation of the perforant path was evaluated in rats that showed robust place learning in the water maze. There was no effect of place learning on the field potential, and field potential measures did not correlate with place learning acquisition measures. In the second approach, the effect of bilateral saturation of LTP on subsequent place learning in the water maze task, begun within 5 minutes of the last LTP session, was evaluated. The effect of kindled seizures evoked bilaterally from the perforant path, or of a single unilateral AD, on acquisition of the water maze task (begun within 10 minutes) were also evaluated. Bilateral LTP saturation did not affect place learning, and the bilateral LTP group learned as readily as controls. In contrast, the kindled and AD groups were severely impaired in their performance of the place learning task. A second day of training in the water maze without any further electrical stimulation indicated that these groups had acquired considerable information on the first day of maze training and were not distinguishable from controls on the second day of training. This indicated that the deficit in these groups on the first day of training was temporary and likely resulted from a temporary perturbation of normal brain function due to the seizures. The results indicate that bilateral saturation of LTP in the dentate gyrus does not affect place learning in the water maze. They also indicate that recent hippocampal seizures, but not kindling, disrupt place learning in this task. PMID- 8353604 TI - Spatial selectivity of unit activity in the hippocampal granular layer. AB - Single neuron activity was recorded in the granular layer of the fascia dentata in freely moving rats, while the animals performed a spatial "working" memory task on an eight-arm maze. Using recording methods that facilitate detection of units with low discharge rates, it was found that the majority (88%) of cells in this layer have mean rates below 0.5 Hz, with a minimum of 0.01 Hz or less. The remaining recorded cells exhibited characteristics typical of the theta interneurons found throughout the hippocampus. Based on several criteria including relative proportion and the relation of their evoked discharges to the population spike elicited by perforant path stimulation, it was concluded that the low-rate cells correspond to granule cells. Granule cells exhibited clear spatially and directionally selective discharge that was at least as selective as that of a sample of CA3 pyramidal cells recorded under the same conditions. Granule cells had significantly smaller place fields than pyramidal cells, and tended to have more discontiguous subfields. There was no spatial correlation among simultaneously recorded adjacent granule cells. Granule cells also exhibited burst discharges reminiscent of complex spikes from pyramidal cells while the animals sat quietly; however, the spike duration of granule cells was significantly shorter than CA3 pyramidal cell spike durations. Under conditions of environmental stability, granule cell place fields were stable for at least several days. Following occasional maze rotations relative to the (somewhat impoverished) visual stimuli of the recording room, granule cell place fields were maintained relative to the distal spatial cues; however, frequent rotations of the maze sometimes resulted in a shift in the reference frame to the maze itself. These observations indicate that granule cells of the fascia dentata provide their CA3 targets with a high degree of spatial information, in the form of a sparsely coded, distributed representation. PMID- 8353605 TI - Effects of glucocorticoids on hippocampal long-term potentiation. AB - The effects of chronic and acute corticosterone (CORT) administration were investigated on hippocampal long-term potentiation (LTP) in the dentate gyrus granule cell layer of the rat. Electrophysiological experiments were performed in vivo under urethane anesthesia. Chronic CORT treatment (40 mg/kg/day) over 21 days decreased LTP compared to vehicle controls, even when LTP was measured 48 hours after cessation of CORT treatment, when serum CORT levels had returned to baseline. A single injection of CORT also decreased LTP compared to vehicle controls, but only when CORT levels were high, since at 48 hours after a single acute CORT injection LTP was not depressed. The decrements in LTP were seen both for the slope of the excitatory postsynaptic potential and for the population spike. Yet CORT had no effects on posttetanic potentiation or neuronal excitability. These findings are consistent with previous reports showing a reduction in LTP in the CA1 field of animals exposed to stress or acute CORT administration. PMID- 8353606 TI - GABA induces a unique rise of [Ca]i in cultured rat hippocampal neurons. AB - GABA evoked a reversible rise of free intracellular calcium concentration ([Ca]i) in cultured rat hippocampal neurons, detected with Fluo-3 fluorescence in a confocal laser scanning microscope. The GABA-evoked change of [Ca]i was mimicked by muscimol and not by baclofen, but was only minimally affected by picrotoxin or bicuculline, indicating that this effect of GABA is not likely to be mediated by activation of GABAB receptor or by a conventional chloride-linked GABAA receptor. GABA-evoked rise of [Ca]i expressed a marked desensitization; only 10-20 minutes after a previous exposure to GABA was the response to a subsequent application fully expressed. This desensitization was not seen in electrophysiological responses to GABA or in [Ca]i changes evoked by NMDA in the same neurons. The GABA response appeared to be developmentally regulated and was seen in 1-7-day old more than in 21-28-day-old cells. It is suggested that GABA evokes a unique change of [Ca]i in young hippocampal neurons. PMID- 8353607 TI - Perineuronal satellitosis in the human hippocampal formation. AB - A previously unreported example of perineuronal satellitosis in the medial CA1 and adjacent subiculum in the human hippocampal formation is described. This phenomenon is characterized by a clustering of glial cells in relation to the perikarya of a subpopulation of neurons in the deep pyramidal layer and around most neurons scattered in the stratum oriens and subcortical white matter. Most of the perineuronal satellite glia were identified as oligodendrocytes based on their nuclear chromatin patterns and antigenic properties. Satellite oligodendrocytes were mostly of the medium dense variety. A type of satellite glia with nuclear features of the dark oligodendrocyte could not be identified unequivocally using the antigenic criteria employed in this study. PMID- 8353608 TI - Hippocampal function in the rat: cognitive mapping or vicarious trial and error? AB - The most prominent hypothesis of hippocampal function likens the hippocampus to a "cognitive map," a term used by a famous learning theorist, E. C. Tolman, to explain maze learning. The usual application of this concept of cognitive map, as it applies to the hippocampus, is to what is called spatial learning, mainly in the radial-arm maze of Olton and the Morris water maze. In a recent Hippocampus Forum, evidence for the cognitive map hypothesis was reviewed in a lead article by Nadel, followed by a series of commentaries by leading investigators of hippocampal function. This speculative commentary offers an alternative not represented in the forum--that the function of the hippocampus in spatial learning is not as a cognitive map, but that it subserves another function proposed by Tolman in his work on simple discrimination learning, vicarious trial and error, based on incipient, conflicting dispositions to approach and avoid. PMID- 8353609 TI - Epilepsy induced collateral sprouting of hippocampal mossy fibers: does it induce the development of ectopic synapses with granule cell dendrites? AB - In the present study, using Golgi and electron microscopy techniques, experimentally induced epilepsy (kindling and kainate treatment) elicited collateral sprouting of mossy fibers in rat hippocampus. Collateral branches invade the hilus, cross the granule cell layer, and distribute throughout the inner third of the molecular layer. These newly developed collaterals may acquire the typical features of mossy fibers including giant fiber varicosities (mousses), although the mean surface of these mousses was thinner in these collaterals than in terminal branches. Granule cell dendrites may develop giant thorny excrescences, suggesting that the targets of these collaterals are granule cells. Giant synaptic boutons appear in the inner third of molecular layer of epileptic rats. These boutons acquire the morphological features of mossy fiber boutons and made multiple synaptic contacts with dendritic spines. The analysis of the profile types suggests that some of the newly developed collateral mossy fibers made hypotrophic synaptic contacts. PMID- 8353610 TI - Neurochemical development of the hippocampal region in the fetal rhesus monkey. I. Early appearance of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex during the first half of gestation (E47 to E90). AB - Although the entorhinal cortex is a key structure connecting the hippocampal formation with the rest of the cerebral cortex, little is known about its early chemoanatomical development in primates. In the present study, a cytoarchitectonic analysis and immunocytochemical detection of somatostatin, neurotensin, parvalbumin, calbindin-D 28K, DARPP-32, as well as tyrosine hydroxylase, dopamine-beta-hydroxylase, and serotonin, were carried out on serial sections of the entorhinal cortex of six rhesus monkey fetuses aged E47 to E90 (gestation period 165 days). At E56 the cortical plate of the entorhinal cortex already exhibited a sublamination; at E64 the lamina dissecans was partly formed, allowing the emergence of the lamina principalis externa and interna, and at E83 most of the regional and laminar subdivisions characteristic of the adult cortex could be identified, except for the rhinal sulcus restricted to a small dimple. The neurochemical development paralleled the early cytoarchitectonic differentiation, both largely preceding that of the neighboring cortical areas. The somatostatin-like immunoreactive innervation, first detected at E56, was very dense as early as E64 and displayed by E83 a laminar distribution similar to that found in the adult. Labeled neurons indicated an intrinsic origin for this innervation but an extrinsic connection might be present as labeled fibers in the subplate of the entorhinal cortex were in continuity with positive fibers in the intermediate zone of the hippocampal formation. A faint neurotensin-like immunoreactivity first detected at E64 became prominent at E83 in the entorhinal cortex but stopped abruptly at the anlage of the rhinal sulcus. The lack of neurotensin-labeled neurons contrasted with their presence in other parts of the hippocampal region and suggested a precocious extrinsic connection. Only rare parvalbumin-LIR neurons were detected at midgestation, whereas calbindin-D 28K was expressed from E47 on in Cajal-Retzius cells and from E56 on in various types of neurons in the cortical plate and subplate. Most characteristic was a category of medium-sized, deeply stained calbindin-LIR neurons, present only in the lamina principalis externa and possibly corresponding to the population of large neurons described by Kostovic et al. (1990, Soc Neurosci Abstr 16:846) in early developing entorhinal cortex of human fetuses. These and probably other neurons were also DARPP-32-positive, suggesting the possibility of an early dopaminergic regulation. Indeed, the monoaminergic innervation of the entorhinal cortex was detected from E56 on and gradually increased in density, displaying areal and laminar differences in the distribution of the dopaminergic, noradrenergic, and serotoninergic afferents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8353611 TI - Phase relationship between hippocampal place units and the EEG theta rhythm. AB - Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroencephalograph theta pattern of rhythmical waves (7-12 Hz) is better correlated with a class of movements that change the rat's location in an environment. During movement through the place field, the complex spike cells often fire in a bursting pattern with an interburst frequency in the same range as the concurrent electroencephalograph theta. The present study examined the phase of the theta wave at which the place cells fired. It was found that firing consistently began at a particular phase as the rat entered the field but then shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This precession of the phase ranged from 100 degrees to 355 degrees in different cells. The effect appeared to be due to the fact that individual cells had a higher interburst rate than the theta frequency. The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry. These results have implications for several aspects of hippocampal function. First, by using the phase relationship as well as the firing rate, place cells can improve the accuracy of place coding. Second, the characteristics of the phase shift constrain the models that define the construction of place fields. Third, the results restrict the temporal and spatial circumstances under which synapses in the hippocampus could be modified. PMID- 8353612 TI - Learning and memory after adrenalectomy-induced hippocampal dentate granule cell degeneration in the rat. AB - Adrenalectomy (ADX) of normal adult rats causes selective hippocampal dentate granule cell degeneration that is prevented by corticosterone. The ability to destroy this one hippocampal cell type noninvasively made it possible to address the role of the dentate granule cells in learning and memory. Four months after ADX, 31 of 45 rats failed to show obvious granule cell loss and displayed behavior in the Morris water maze that was similar to 16 sham-operated control rats and 16 ADX rats maintained on corticosterone throughout the study. Conversely, 14 of the 45 ADX rats experienced a loss of granule cells that varied from minimal to extensive. Although there were no obvious differences between groups in motoric and motivational characteristics or search strategies, ADX rats with moderate to extensive granule cell loss acquired place learning slightly slower than controls or ADX rats with minimal or no obvious cell loss. Furthermore, the ADX rats with moderate to extensive cell loss were temporarily impaired following alteration of either intramaze or extramaze cues compared to controls. In contrast, the rats with granule cell loss remembered an old place and learned a new place as quickly as controls. These results suggest that a normal complement of dentate granule cell may not be necessary for the acquisition or retention of spatial information in the Morris water maze. PMID- 8353613 TI - Activation, travel distance, and environmental change influence food carrying in rats with hippocampal, medial thalamic and septal lesions: implications for studies on hoarding and theories of hippocampal function. AB - Rats transport food from exposed areas to covered areas where they eat it or leave it. Although there is evidence that limbic structures play a role in food transport, their role is controversial. Here it was found that although many rats with large hippocampal, septal/diagonal band of Broca or dorsomedial thalamic lesions did not carry food but ate it where they found it, a few presentations of an auditory stimulus could restore food carrying. Once restored, most features of food carrying in hippocampal rats were normal in relation to food presentation schedules, deprivation levels, ambient illumination, circadian cycles, food size, and eating times. Nevertheless, food carrying impairments re-emerged when the testing environment was changed. Hippocampal rats were also excessively responsive to increases in travel distance and stopped carrying food at distances over which control rats would still carry large food pellets. Auditory stimulation did not restore food carrying over long travel distances. The findings that sensory stimulation, environmental change, and travel distance influence food carrying probabilities in rats with limbic system lesions is discussed in relation to research on limbic control of food hoarding and theories of limbic system function. PMID- 8353614 TI - Maps, routes, and the hippocampus: a neural network approach. AB - This study describes hippocampal participation in maze navigation in terms of a real-time, biologically plausible neural network. The system is composed of (1) a goal-seeking mechanism, (2) a cognitive map system, and (3) a route system. The goal-seeking mechanism displays exploratory behavior until either the goal is found or a sufficiently strong prediction of the goal is generated. The cognitive map is a topological map that stores associations between places and views of accessible places, and between places and reward. The route system establishes associations between cues and reward. Both systems compete with each other to establish associations with the reward, with the cognitive system generally overshadowing the route system. In agreement with previous models, it is assumed that the hippocampus modulates the storage of cognitive maps in cortical areas and mediates the competition between cognitive maps and route systems. After hippocampal lesions, animals navigate through mazes making use of the route system. Computer simulations show that the network effectively describes latent learning, detour behavior, and place learning in normal and hippocampal- and cortical-lesioned animals. PMID- 8353615 TI - Sources of variation in phonetograms. AB - Despite the growing popularity of the phonetogram or F0-SPL Profile in the United States and its continuing use in Europe, it is generally acknowledge that a wide range of results are obtained by different investigators using the technique. Nonuniformity of results calls into question the basic validity of the method as a descriptor of vocal function limits. This article reviews some of the more common diversities in methods among investigators and suggests that variation of results in voice profiles may be as much an indication of nonstandardization of technique as in the inherent variability of subjects. PMID- 8353616 TI - Phonatory control in male singing: a study of the effects of subglottal pressure, fundamental frequency, and mode of phonation on the voice source. AB - This article describes experiments carried out in order to gain a deeper understanding of the mechanisms underlying variation of vocal loudness in singers. Ten singers, two of whom are famous professional opera tenor soloists, phonated at different pitches and different loudnesses. Their voice source characteristics were analyzed by inverse filtering the oral airflow signal. It was found that the main physiological variable underlying loudness variation is subglottal pressure (Ps). The voice source property determining most of the loudness variation is the amplitude of the negative peak of the differentiated flow signal, as predicted by previous research. Increases in this amplitude are achieved by (a) increasing the pulse amplitude of the flow waveform; (b) moving the moment of vocal fold contact earlier in time, closer to the center of the pulse; and (c) skewing the pulses. The last mentioned alternative seems dependent on both Ps and the ratio between the fundamental frequency and the first formant. On the average, the singers doubled Ps when they increased fundamental frequency by one octave, and a doubling of the excess Ps over threshold caused the sound pressure level (SPL) to increase by 8-9 dB for neutral phonation, less if mode of phonation was changed to pressed. A shift of mode of phonation from flow over neutral to pressed was associated with a reduction of the peak glottal permittance i.e., the ratio between peak transglottal airflow to Ps. Flow phonation had the most favorable relationship between Ps and SPL. PMID- 8353617 TI - Superimposition of speaking voice characteristics and phonetograms in untrained and trained vocal groups. AB - This study details a comparison of the speaking F0 and intensity values of young male and female adults with and without vocal training, as well as the superimposition of the speaking F0 and intensity data upon phonetograms. Results indicated that (a) trained vocalists have similar mean speaking F0's than do untrained vocalists, but exhibit significantly greater speaking F0 ranges than do untrained vocalists; (b) trained vocalists are significantly greater mean intensity levels in speech, as well as significantly greater speaking intensity ranges than do untrained vocalists; (c) the mean speaking F0 for both trained and untrained vocalists was found in the vicinity of the 5-7% frequency level of the entire phonational F0 range (in Hz), equivalent to 12-16% of the phonational F0 range in semitones; (d) the overall speech area (mean speaking F0 and minimum and maximum speaking F0 peaks) was found in the lower 23-31% of the entire phonational F0 range (in semitones), with the untrained subjects utilizing the lower 25% of the phonational range (in semitones) and the trained subjects extending this area to the lower 28-31%; and (e) significant correlations were observed between the total intensity range and intensity range used in speech in trained female vocalists and between total F0 range and speaking F0 range in the combined trained male and female group. These results have important implications for the use of the phonetogram, as well as the clinical applicability of vocal training exercises in various speech and voice therapy cases. PMID- 8353618 TI - Airflow measurements: theory and utility of findings. AB - The biomechanical movements of vocal structures are shown to control flow of expiratory air for the production of speech sounds. Laminar and turbulent air flow are discussed as they relate to sound generation. Theoretic and therapeutic utility of air flow profiles in differentiating linguistic contrasts and vocal characteristics are discussed along with considerations of relative utility and accuracy for various flow-measuring devices and strategies. PMID- 8353619 TI - Inverse-filtered air flow and EGG measures for sustained vowels and syllables. AB - The purpose of this investigation was to compare the effects of two speaking tasks on laryngeal measures obtained from inverse-filtered air flow and electroglottograph (EGG) waveforms. Flow amplitude, air flow duty cycle, EGG duty cycle, and fundamental frequency were measured for normal young and aged adults during vowel prolongation and syllable repetition. There were significant between task differences for flow amplitude and fundamental frequency. Variability appeared no greater for syllable repetition than vowel prolongations. Syllable repetition was slightly better than vowel prolongation for differentiating the vocal behaviors of aged and young speakers. Between-task relationships were strong for fundamental frequency and more moderate for the other laryngeal measures. It was concluded that syllable repetition would be preferable to vowel prolongation for measurement of aerodynamic and EGG parameters and that findings could be generalized across speaking tasks for fundamental frequency but not air flow and duty cycle measures. PMID- 8353620 TI - Laryngeal and respiratory activity during vocalization in macaque monkeys. AB - The present study describes the laryngeal and respiratory muscle activity associated with vocalizations in macaque monkeys. During the bark vocalization, a short, aperiodic call, the cricothyroid, thyroarytenoid, rectus abdominis, and intercostals were active while the posterior cricoarytenoid and diaphragm were quiet. During the coo vocalization, a longer, clear call, the cricothyroid, thyroarytenoid, intercostals, rectus abdominis, and diaphragm were active. In one monkey, the posterior cricoarytenoid was also active during the call, while in another monkey it was not. Laryngeal muscle activity was correlated with the amplitude and duration of the coo call. Results suggest that the amplitude and duration differences between calls are determined primarily by laryngeal modification of the airflow, and that the differences in posterior cricoarytenoid activity may be due to differences in voice intensity. PMID- 8353621 TI - Vocal attrition in voice students: survey findings. AB - A questionnaire designed in part to survey symptoms of vocal attrition and possible factors contributing to it was administered to 79 university female voice students. Of the 74 students (94%) completing the questionnaire, 10 (13%) were free of symptoms, 19 (26%) had few (one or two), and 45 (61%) had multiple (three or more) symptoms. Thirty-five students (47%) had sought medical help for voice problems since they began their singing career. Students with multiple symptoms were significantly more likely to (a) be bothered, frustrated, worried, depressed, or anxious about their voice; (b) quit performance, forgo audition, limit their repertoire, or quit singing altogether; (c) speak in a voice that is too low in pitch; and (d) have a general tendency to worry, be depressed or anxious, or have mood swings. The clinical implications of these and other findings are discussed. PMID- 8353622 TI - A critical view of the yawn-sigh as a voice therapy technique. AB - The purpose of this study was to take a critical look at a voice therapy technique known as the yawn-sigh. The voiced sigh as an approach in voice therapy has had increased use in recent years, particularly with problems of vocal hyperfunction. In this study, the physiology of the yawn-sigh was studied with video nasoendoscopy in eight normal subjects; their taped voices were also studied acoustically for possible fundamental frequency and format changes in producing selected vowels under normal and sigh conditions. Although each subject was given a model by the examiner of a yawn-sigh, one of the eight subjects could not produce a true yawn-sigh. Endoscopic findings for seven of the eight subjects performing the yawn-sigh demonstrated retracted elevation of the tongue, a lower positioning of the larynx, and a widened pharynx. Acoustic analyses for the seven subjects producing the sigh found a marked lowering of the second and third formants. Implications for using the yawn-sigh in voice therapy are given, such as using a modified "silent" yawn-sigh, as an easy method for producing greater vocal tract relaxation. PMID- 8353623 TI - Sarcoidosis of the larynx: preserving and restoring airway and professional voice. AB - Professional voice users may present with disastrous dysponia and life threatening upper airway disturbances due to a rare condition. Two teachers demonstrated extrathoracic obstructive laryngeal lesions by videolaryngoscopy and pulmonary function flow-volume loops. A characteristic "honking" voice and edematous, pink, diffuse turban-like enlargement of the supraglottic structures are considered pathognomonic of laryngeal sarcoidosis. Diagnosis was confirmed by biopsies, and clinical and radiologic findings. Sarcoidosis is a variable, disseminated disease involving many body organs, self-limited or progressive, with frequent exacerbations and remissions, affecting the larynx in 0.5-1.4% of patients. Spinal cord involvement demonstrated by new magnetic resonance imaging techniques can be heralded by voice changes detected in professional voice users. Systemic corticosteroid therapy combined with intralesional steroid injections and microendoscopic surgery, with or without tracheostomy, preserved and restored both professional voice and airway. PMID- 8353624 TI - Overtone singing: productive mechanisms and acoustic data. AB - Overtone singing is where one person sings in two voices, the first voice represented by the fundamental and the second by an enhanced harmonic. Overtone singing is performed in chest register. Tuning of the first or second formant and a reduction of the formant bandwidth down to 20 Hz make harmonics prominent. Narrowing the pharynx, velar constriction, variation of the small mouth opening, and a tension of the walls of the mouth cavity are used. Changing prominent harmonics has the effect of creating an overtone melody with sustained tones, tone steps, and trillos. PMID- 8353625 TI - Laryngeal biomechanics: an overview of mucosal wave mechanics. AB - The biomechanics of wave propagation in viscoelastic materials can be useful in understanding the nature of normal and pathologic vocal fold vibration. Mucosal wave movement is the primary means by which the larynx transforms the egressive pulmonary air flow into sound. This short tutorial describes a number of concepts fundamental to the understanding of the vocal fold traveling wave. The displacement velocity of the vocal folds is shown to be proportional to the wave speed, which in turn is proportional to the elastic modulus or stiffness of the vocal folds. Finally, a few cases of unilateral paralysis are used to demonstrate how vocal fold stiffness, entrainment, and degree of vocal fold closure interact to create the complex vibratory patterns that occur in disordered laryngeal states. It is emphasized that surgical voice restoration must consider these properties of the mucosal wave to improve phonatory function. PMID- 8353626 TI - Perceptual evaluations of voice scatter in unison choir sounds. AB - The preferences of experiences listerners for pitch and formant frequency dispersion in unison choir sounds were explored using synthesized stimuli. Two types of dispersion were investigated: (a) pitch scatter, which arises when voices in an ensemble exhibit small differences in mean fundamental frequency, and (b) spectral smear, defined as such dispersion of formants 3 to 5 as arises from differences in vocal tract length. Each stimulus represented a choir section of five bass, tenor, alto, or soprano voices, producing the vowel [u], [a], or [ae]. Subjects chose one dispersion level out of six available, selecting the "maximum tolerable" in a first run and the "preferred" in a second run. The listeners were very different in their tolerance for dispersion. Typical scatter choices were 14 cent standard deviation for "tolerable" and 0 or 5 cent for "preferred." The smear choices were less consistent; the standard deviations were 12 and 7%, respectively. In all modes of assessment, the largest dispersion was chosen for the vowel [u] on a bass tone. There was a vowel effect on the smear choices. The effects of voice category were not significant. PMID- 8353627 TI - Quantitative evaluation of phonetograms in the case of functional dysphonia. AB - According to the laryngeal clinical findings, figures making up a scale were assigned to vocally trained and vocally untrained persons suffering from different types of functional dysphonia. The different types of dysphonia--from the manifested hypofunctional to the extreme hyperfunctional dysphonia--were classified by means of this scale. Besides, the subjects' phonetograms were measured and approximated by three ellipses, what rendered possible the definition of phonetogram parameters. The combining of selected phonetogram parameters to linear combinations served the purpose of a phonetographic evaluation. The linear combinations were to bring phonetographic and clinical evaluations into correspondence as accurately as possible. It was necessary to use different kinds of linear combinations for male and female singers and nonsingers. As a result of the reclassification of 71 and the new classification of 89 patients, it was possible to graduate the types of functional dysphonia by means of computer-aided phonetogram evaluation with a clinically acceptable error rate. This method proved to be an important supplement to the conventional diagnostics of functional dysphonia. PMID- 8353628 TI - Belting and pop, nonclassical approaches to the female middle voice: some preliminary considerations. AB - There is a commonly perceived difference in the sound produced in the approximate range D4-D5 by female singers in the western opera and concert tradition, on the one hand, and certain other styles, including rock, pop, folk, and some Broadway musicals, on the other. The term "belting" is sometimes used to refer to at least one approach to such "nonclassical" singing. In this study, based on spectrographic, electroglottographic, and sub- and supraglottal pressure measurements on representative voices of the "operatic" and "nonclassical" tradition, acoustic and laryngeal differences between the two traditions are described, and an objective, specific definition of "belting" is offered. PMID- 8353629 TI - Vocal matching of frequency modulation in synthesized vowels. AB - Nine male singers attempted to match rates and extents of synthesized vocal vibrato at low, middle, and high pitch levels. The results showed that on average, the singers were able to match rates of 3, 5, and 7 Hz within 13%. It was difficult for the singers, however, to match extents of 0.5, 1.0, and 1.5 semitones. Thus, the results indicated singers' reasonably good ability to match rates but, contrary to prevalent opinions, not extents of vocal vibrato. PMID- 8353630 TI - Intervention with young voice users: a clinical perspective. AB - This diverse group is described in relation to life stage, short- and long-range performance objectives, and lifestyle factors pertinent to vocal health. Physical, behavioral, cognitive, and psychosocial issues relevant to assessment and intervention will be addressed. The possible dissonance between a clinician's developmental perspective and a client's immediate pragmatic concerns is discussed. In addition, the specific challenges of dealing with adolescents (e.g., the influence of the peer group, the emergence of autonomy, the redefinition of relationships with significant adults, and the vulnerability of the mechanism) are related to clinical problem solving. PMID- 8353631 TI - Perceptual-acoustic relationships in spasmodic dysphonia. AB - Perceptual ratings were obtained from voice samples of 19 patients with adductor spasmodic dysphonia before and 1 week after unilateral treatment with Botulinum toxin. Five experienced listeners judged samples of sustained phonation using a seven-point equal-interval scale. The perceptual parameters assessed were overall severity, strain-strangled voice quality, and breathiness. Perceptual results were related to the standard deviation of fundamental frequency and the voice break factor, two acoustic parameters previously shown to be significantly improved following Botulinum toxin injection. Results indicate that in general the spasmodic dysphonia voice is perceived as less severe, less strain-strangled, and more breathy 1 week after treatment. Interrelations among perceptual parameters and relationships with acoustic analyses are discussed. PMID- 8353632 TI - Long-term results of recurrent laryngeal nerve resection for adductor spasmodic dysphonia. AB - From a total of 43 adductor spasmodic patients over a 10-year period, 11 underwent resection of a portion of the recurrent laryngeal nerve on one side. The initial results were excellent but a varying degree of recurrence took place in 8 patients. In 4, a reoperation was done. At the final follow-up, 2-8 years after the primary operation, 4 patients were no longer suffering from spasmodic dysphonia, another 5 were better off than before surgery, and 1 remained unchanged. Only 1 was worse off. Electromyographic findings indicated that the recurrence of symptoms was due to regeneration of the nerve fibers. PMID- 8353633 TI - Tracking change in dysphonia: a case study. AB - This longitudinal case study of a woman with nodules examines the relationship between clinical and acoustic measures of change. Relative changes in voice quality, vocal fold condition, and patient symptoms were compared to measures of mean fundamental frequency (MFF), jitter, and fundamental frequency range (FFR). Seven assessments were performed over a 2-year period. The findings indicated that voice quality judgments tended to relate to changes in degree of vocal fold pathology and patient report of vocal function. However, acoustic measures of MFF, FFR, and jitter did not relate to measures of clinical change. The discussion focuses on explanations for the acoustic findings, the need for using connected speech samples for perceptual and acoustic analysis, and a suggestion for future study. PMID- 8353634 TI - Vocal fold exposure in phonosurgery. AB - A difficult laryngeal exposure is made easier by placement of the patient's head and neck into the Boyce-Jackson "sniffing position" and then flexing them further if necessary, by selection of a laryngoscope appropriate to the patient and to the triangular glottic shape, by placement of the laryngoscope along the path of least resistance, by use of a true suspension device in order to apply the force for laryngoscopy towards the larynx and away from the teeth and gums, and by allowing time for the force to work. With these techniques, an easy exposure is made almost perfect. The true vocal folds are exposed from vocal process to anterior commissure without the need for external pressure, the endotracheal tube remains out of sight between the arytenoids, and there is no risk to the teeth, gums, and cervical spine. PMID- 8353635 TI - Vocal tract acoustics. AB - This paper considers the topic of vocal tract acoustics from the three perspectives: (a) the acoustic theory of speech production; (b) contemporary laboratory methods for acoustic analysis, and (c) measurement of the acoustic signal of speech. Linear source-filter theory is the standard acoustic theory of speech production and is the foundation for remarkable advances in the analysis and synthesis of speech. Digital signal processing, the dominant laboratory method for speech analysis, enables the acquisition and recording of the acoustic speech signal but also implements quantitative algorithms largely based on linear source-filter theory. Measurements of the acoustic signal reflect the acoustic theory of speech production, laboratory methods for signal analysis, and principles of experimental phonetics. Basic issues in the three domains of theory, laboratory methods, and measurement are summarized as they pertain to the interests of the voice scientist, voice clinician, and voice teacher. PMID- 8353636 TI - That golden voice--talent or training? AB - This article is an updating and expansion of a lecture presented at the Thirteenth Symposium on the Care of the Professional Voice, New York, June 1984; a somewhat limited version of the manuscript was published in the Transcripts of that symposium. Basically, an attempt will be made by an observer from another field to lay the groundwork for the better understanding of the "voice teacher." Accordingly, some of the dialogue to follow may be a little informal; it certainly is interpretive. The latter portion of the discussion will involve suggestions/illustrations that may be useful in further enhancing this somewhat underrated field and bonding it to others. While the comments found below reflect only the opinions of the author, it is fair to state that most of them have been articulated by others. PMID- 8353637 TI - Physical definition of the "flageolet register". AB - The highest "register" of the female singing voice, often called the "flageolet register" (also called "flute register," "bell register," etc., as well as the misleading term "whistle register"), is broadly recognized by voice pedagogues, but not generally defined in terms that are adequate for objective description. This article presents a description of characteristic patterns of vocal fold movement and of vocal tract formants that are specific for the register. Measurements are made by electroglottograph, pharyngeally placed wide-band pressure transducers, and an external microphone in professional soprano subjects who are adept in using this register. PMID- 8353638 TI - Supralaryngeal muscle activity during sustained vibrato in four sopranos: surface EMG findings. AB - Four classically trained sopranos, aged 22-41 years, sustained a vibrato at a comfortable loudness level, and at different vowels (/u/, /i/, or /a/) and pitch levels (220, 277, 349, 440, 554, 698, or 880 Hz). Pairs of surface electrodes were placed on each singer's right side over the submandibular region, the thyroid cartilage, mandibular ramus, and upper lip to record electromyographic (EMG) activity from the anterior suprahyoid (ASH), extralaryngeal (ELAR), massetter (MAS), and perioral (PER) muscles, respectively. A headset-mounted miniature microphone transduced the voice, and a Kay Visi-Pitch extracted the voice fundamental frequency (F0). The output of the Visi-Pitch, a voltage analog of the F0 (VF0), and the EMG signals were digitized, the EMG signals rectified and smoothed, and the VF0 and smoothed EMG signals were subjected to Fast Fourier Transform (FFT) analysis. Spectral peaks in the FFT records indicated vibrato related activity in the ASH and ELAR muscles, with occasional vibrato-related activity in the MAS and PER muscles. The role of supralaryngeal muscles in vibrato is discussed. PMID- 8353639 TI - Phonational profiles of female professional singers and nonsingers. AB - Measures of the SFF, vocal intensity, phonational range, and habitual pitch level are reported for 39 professional singer and 39 nonsinger females, who were divided into three age groups (young, middle, and old age), with the professionals further divided into sopranos and altos. Each read the "Rainbow Passage" and spoke extemporaneously, from which measures of the SFF and vocal intensity were calculated; phonational range and habitual pitch levels were also determined. No significant differences were noted between the reading and speaking tasks. The SFF and intensity levels were significantly higher for the professionals in comparison to the nonsingers, but only for certain age groups. Moreover, whereas the nonsinger SFF levels varied significantly as a function of age, those for the professional singers did not. Although trends occurred, no significant differences were found for the mean phonational range or habitual pitch levels when the professionals and nonsingers were compared. PMID- 8353640 TI - Short-term variation of subglottal pressure for expressive purposes in singing and stage speech: a preliminary investigation. AB - According to previous investigations, subglottal pressure in singing is adapted not only to loudness but also to fundamental frequency. Here the significance of musical expression to subglottal pressure is analyzed in terms of alternations between stressed and unstressed bar positions. Esophageal pressure was recorded together with the audio signal in a male and a female professional singer using a paranasally introduced pressure transducer while the subjects performed vocal exercises. Also, the subjects gave examples of actors' speech by reading poetry aloud. The results show that subglottal pressure can be used for stressing the first beat in bars and also for increasing the sound level in voiced consonants in actor's speech. PMID- 8353641 TI - Interactive effects of local smoothing window size and fundamental frequency on shimmer calculation. AB - Slow amplitude modulation of human voice was approximated by a sinusoidal wave. The theoretical effects of smoothing window size, F0, and modulation frequency on window amplitude average as well as calculated shimmer were mathematically derived. Subsequently, the theoretical predictions were tested using idealized and real voice signals from normal speakers. The theoretical and experimental results suggest that shimmer (when calculated using a smoothing window) is a function of window duration and modulation frequency. Window duration when defined as a constant number of pitch periods varies from speaker to speaker depending on their F0. It may not be desirable to use local smoothing windows with a constant number of cycles for shimmer computation, especially if voices with known low-frequency amplitude modulations but notably different fundamental frequencies are compared. PMID- 8353642 TI - Effects of the manual laryngeal musculoskeletal tension reduction technique as a treatment for functional voice disorders: perceptual and acoustic measures. AB - During a 2-year period, 17 patients with "functional dysphonia" were assessed and managed in a hospital setting. A single treatment approach, known as manual laryngeal musculoskeletal tension reduction, was employed. The effects of the therapy regimen were analyzed using perceptual and acoustical measures of vocal function. The results indicated a significant change in the direction of "normal" vocal function in the majority of patients within one treatment session. Perceptual measures of severity were consistently more likely to be rated as normal following treatment. Acoustic measures of voice confirmed significant improvements in jitter, shimmer, and signal-to-noise ratio (SNR). Results are discussed in terms of the clinical utility and effectiveness of this treatment approach for functional dysphonia. PMID- 8353643 TI - Pushing exercise program to correct glottal incompetence. AB - A voice therapy program using pushing exercises to correct glottal incompetence is described. The program utilizes various types of instrumentation to determine whether or not a given patient is likely to benefit from the treatment. The program also provides feedback of target voices. Three cases with incomplete glottal closure and subsequent vocal dysphonia characterized by an asthenic breathy quality are used to illustrate the program. Details of the program, termination criteria, and problems and precautions learned from treating 29 patients over a 3-year period are presented. PMID- 8353644 TI - Voice: a historical perspective. L. V. Shcherba and the concept of linguistic experimental phonetics. PMID- 8353645 TI - Russian vowels in qualitative and quantitative respects. PMID- 8353646 TI - Safety of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation. AB - The purpose of this study was to determine whether a new ultrafiltrated whey hydrolysate infant formula, Profylac, could be administered safely to children with cow milk protein allergy/intolerance. Profylac has a stated molecular weight of < 8 kD and at least 30,000 times reduced antigenicity which is controlled by a combination of ELISA-techniques and immunochemical methods. The study comprised 66 children with cow milk protein allergy/intolerance diagnosed by controlled elimination/challenge procedures. The children were aged 1 month-14.5 years, median 1 11/12 years and 15 were below 1 year. Thirty-five of these children had proven IgE-mediated reactions (cow milk protein allergy). Sixty-one of the children had at least two different symptoms and 31 had concomitant allergies to other foods and/or inhalants. All 66 children underwent and tolerated open, controlled challenges with Profylac. A total of 64 children continued having Profylac daily for at least 3 months and 58 for at least 6 months after challenge. Nine of the children older than 1 year did not like the taste and only had Profylac in minor amounts. No side effects were registered. Fifteen of the infants were below 1 year of age, and this group was compared with an age matched group of 16 infants challenged with and fed an extensively hydrolysed casein hydrolysate, Nutramigen. All the infants in these two groups accepted and tolerated Profylac and Nutramigen, respectively, and no side effects were registered. Among the 35 patients with IgE-mediated reactions 6% (2/35) had positive skin prick tests and 11% (3/28) had specific IgE class 2 against Profylac, 2 of the latter before intake of Profylac.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353647 TI - Interferon-gamma production by cord-blood mononuclear cells is reduced in newborns with a family history of atopic disease and is independent from cord blood IgE-levels. AB - For newborn children both elevated serum IgE levels in the cord blood and a positive family history of atopic disease have been shown to be risk factors for the manifestation of atopic diseases. In adult patients with atopic dermatitis, in vitro interferon-gamma (IFN-gamma) production is reduced and a negative correlation with serum IgE levels has been shown. We have now raised the question if newborn infants at risk for the development of atopic disease have similar abnormalities of cytokine production at birth. In vitro production of interleukin 2, interleukin 6 and interferon-gamma by peripheral blood mononuclear cells was measured in 53 newborns: 21 had cord blood IgE levels above 0.9 kU/l, 21 had a positive family history, 7 had both elevated IgE and a positive family history; 18 newborns with no identifiable risk for atopic disease served as controls. Umbilical cord blood mononuclear cells were stimulated with PHA or monoclonal antibody OKT3. In vitro production of interleukin 2 and 6 was comparable in all groups. Compared to controls IFN-gamma production of peripheral mononuclear cells (PBMC) from newborns with elevated cord blood IgE was not different, but PMBC from newborns with a familial risk showed a significant decrease in PHA induced IFN-gamma production (p < 0.005, U-test). No correlation between umbilical cord blood IgE and diminished IFN-gamma production was found in newborns with or without a positive family history. We conclude that immunoregulatory abnormalities in newborns of atopic families are detectable already at birth and are unrelated to cord blood IgE. PMID- 8353648 TI - Wiskott Aldrich syndrome: an immunodeficiency syndrome not rare in Western Australia. AB - Wiskott Aldrich syndrome, a combined cellular and humoral X-linked immunodeficiency, is generally considered to be rare. The aim of this study was to ascertain the true prevalence in the paediatric population in Western Australia, describe the clinical features, and summarise the current literature on this unusual condition. All cases of Wiskott Aldrich syndrome presenting to Princess Margaret Hospital in Perth during the period from January 1960 to January 1990 were identified by a retrospective review of case records and by interviewing hospital immunology, haematology and general clinical staff. Nine cases of Wiskott Aldrich syndrome are described, demonstrating that the prevalence of Wiskott Aldrich syndrome in Western Australia is nine times that expected from previous reports. Death occurred in a number of patients before the correct diagnosis was recognised. The clinical features in this group are quite variable. Low isohaemagglutinins, elevated IgE, blunted DTH skin multitest, and very low CD8 numbers are however consistent features. Wiskott Aldrich syndrome may be more prevalent than previously recognised, and should be considered in males with thrombocytopenia and infection. PMID- 8353649 TI - Budesonide: safety and efficacy aspects of its long-term use in children. AB - Fifty-two asthmatic children aged 4 to 13 years (mean 9.6) were enrolled in this open 12-month study of budesonide, 200 mcg bid, administered by tube-spacer inhaler (INHALET, ASTRA DRACO). The aim of the study was to assess long-term safety, as well as efficacy, of budesonide in children whose asthma was not adequately controlled by their current therapy. Children attended the clinic every three months for assessment of lung function and height. In addition, an adrenal function test and routine clinical chemistry and haematology were performed. Parents completed diary cards once each week, recording the child's PEF, asthma symptoms, beta 2-agonist consumption and other medication (no prophylactic drugs or other inhaled steroids were allowed and oral steroids were used for emergency treatment only). There were significant increases in all clinic lung function tests (baseline to last visit) and in diary card PEF (first 3 months vs last 3 months). These were accompanied by decreases in asthma symptoms and use of beta 2-agonists or other medication. There was no indication that growth was affected by study treatment and basal adrenal function (basal cortisol) did not change significantly throughout the study. The adrenal response to Synacthen had actually increased significantly by the end of the study. No serious adverse events were associated with budesonide treatment. In conclusion, regular budesonide therapy was associated with a significant improvement in lung function and symptoms over one year. Budesonide was well-tolerated by the children and appeared to have no adverse influence on either growth or adrenal function. PMID- 8353650 TI - Effect of disodiumcromoglycate on intestinal permeability changes and clinical response during cow's milk challenge. AB - Oral disodiumcromoglycate (DSCG) has been used for many years in the prevention of food allergic reactions. The reported effectiveness varies widely and little is known about the mode of action. The aim of this study was to evaluate the effect of DSCG pretreatment (2 x 100 mg) on intestinal permeability (IP), as measured with a sugar absorption test (SAT), in relation to the clinical response during food challenge in 30 children suspected of cow's milk allergy. In the SAT the urinary Lactulose/Mannitol (L/M) ratio was measured after oral administration of these compounds. DSCG pretreatment did not alter the number of clinically positive challenges. Children with clinically positive challenges showed a significant increase in the L/M ratio with placebo pretreatment as compared to children with clinically negative challenges (p = 0.0008). This difference was reduced to nonsignificant levels after DSCG pretreatment (p = 0.07). We conclude that DSCG in this dosage probably reduces the local intestinal response but does not prevent the extraintestinal reactions. PMID- 8353651 TI - Usefulness of neonatal eosinophil counts as a marker of atopy? AB - Eosinophil count (EC) were obtained from 312 newborns with and 172 without family history of atopy (FHA). The EC were higher in infants with than without FHA. Elevated EC were recorded in babies of parietaria sensitive mothers born in the spring, as compared to other seasons. The predictive value of EC with regard to development of atopic diseases up to 18 months of age was prospectively studied in 103 newborns with FHA. Using 5 x 10(8) cells/l as cut-off level the predictive allergy value was 41%. Elevated EC appears to be a marker of atopy in newborns. PMID- 8353652 TI - Are hypodense eosinophils in children activated or immature? AB - In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, be due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophils. In this study we determined the levels of ECP in serum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (sIL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils. PMID- 8353653 TI - Why do asthmatic children need referral to an emergency room? AB - Asthmatic attacks continue to be a major cause of referral to the emergency room (ER), despite currently available effective treatments. We have prospectively evaluated 100 consecutive children who were referred to the ER with acute asthma and were followed by their primary physicians. Only 46% were able to recognize acute attacks, and 26% had the knowledge and skills for self-management. The prophylactic therapy recommended was usually appropriate, but the compliance was poor and mean serum theophylline levels (STL) was 6.8 micrograms/ml, with subtherapeutic values (< 10 micrograms/ml) in 44 (88%). We studied an additional group of 50 consecutive children who were on a routine follow-up in the hospital asthma clinic. All were examined periodically and were instructed on the disease. The compliance of these children was much better and STL were within the therapeutic range in 73%, significantly higher than in the ER patients (p < 0.001). Their need for ER treatment or hospitalization was much lower than the former group. Poor compliance is a major factor causing referral of asthmatic children to ER, and careful education can improve patient compliance with reduced referral and subsequent hospitalization. PMID- 8353654 TI - Modulation of human eosinophil chemotaxis and adhesion by anti-allergic drugs in vitro. PMID- 8353655 TI - The eosinophil granulocyte in allergic inflammation. PMID- 8353656 TI - The therapeutic index of antihistamines. PMID- 8353657 TI - The role of food allergy and eosinophils in atopic dermatitis. PMID- 8353658 TI - Is there a place for antihistamines in the treatment of perennial asthma? PMID- 8353659 TI - Cetirizine in allergic rhinitis. PMID- 8353660 TI - A placebo-controlled trial of cetirizine in seasonal allergic rhino conjunctivitis in children aged 6 to 12 years. AB - A total of 124 children of both sexes aged between 6 and 12 years with pollen associated rhino-conjunctivitis were included in a multicentre double-blind study of parallel group design to compare the effects of cetirizine 10 mg daily, given as 5 mg morning and evening for 2 weeks, with those of placebo of identical appearance. Rhinorrhea, sneezing, nasal obstruction and nasal and ocular pruritus were evaluated using symptom scores by patients on daily self-evaluation cards and by investigators who, in addition, made a global evaluation at the end of treatment. Appropriate wash-out periods for previous medicines were observed. Unchanged treatment of asthma was allowed and inhaled corticosteroids were continued in 3 placebo patients. Compliance was checked and found to be less than 80% of the prescribed dosage in 2 cetirizine patients. The mean percentage of study days when symptoms were absent or at the most mild (i.e. present but not disturbing), as reported daily by the patients, was significantly greater with cetirizine (56.2%) than placebo (29.7%). This 26.5% difference was considered clinically significant. The value of this method of expressing treatment effects in allergic rhinitis is discussed. Improvement in maximum symptom scores (severest symptoms) assessed by investigators was better for cetirizine than placebo after treatment for 1 week and 2 weeks. Improvement in individual daily symptoms was greater for cetirizine than placebo after a few days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353661 TI - Allergic inflammation. AB - A greater understanding of the basic mechanisms of allergic inflammation is pertinent to the development of new treatments. Previous studies have focused on the role of mediators of hypersensitivity and effector cells, including mast cells and eosinophils. Recent evidence suggests that IgE-dependent activation and tissue eosinophilia are under the local regulation of distinct cytokines. Originally described as products from T lymphocytes, these peptide messengers are produced by alternative cells, including mast cells, eosinophils and the respiratory epithelium. In vitro studies in murine models and using cloned human T lymphocytes indicate the preferential production of "Th2-type" cytokines, including interleukin-4 (IL-4) and IL-5. This review considers the evidence from in vivo studies in humans that "Th2-type" cytokines have a primary role in orchestrating both IgE-dependent events and local tissue eosinophilia. Novel therapeutic approaches might include a broad strategy directed against T lymphocytes, including the use of immunosuppressive agents or anti CD4 antibodies or more precise targeting of IL-4 and/or IL-5. PMID- 8353662 TI - Sternal fractures. AB - Sternal fractures have become more common since the introduction of seat belt legislation. However, the injury often heals well with minimal or no sternal deformity. Morbidity and mortality in patients with fractures of the sternum are usually due to other organ injuries. PMID- 8353663 TI - Management of pain in thoracic surgery. AB - Severe pain after thoracotomy is the most important factor responsible for ineffective ventilation, ineffective cough, and impaired ability to sigh and to breathe deeply. Effective analgesia minimizes and may even reverse the expected decline in pulmonary function and also prevents postoperative pulmonary complications. PMID- 8353664 TI - Connective tissue diseases: advances in diagnosis and management. AB - Connective tissue diseases encompass a group of multisystem inflammatory syndromes whose pathogenesis is thought to be autoimmune. They are all associated with the production of autoantibodies that bind to predominantly intracellular antigens. We will describe recent advances that have led to improved classification and more accurate prognosis. PMID- 8353665 TI - Management of uterine fibroids. AB - Until recently the management of uterine fibroids has been exclusively surgical in the form of either hysterectomy or myomectomy. The development of minimally invasive techniques and the introduction of LHRH agonists has allowed more conservative management to maintain or restore fertility. PMID- 8353666 TI - Late problems faced by childhood cancer survivors. AB - One in 650 children will develop cancer by the age of 15 years, of whom 50-60% will be cured. Early recognition and appropriate management of the long-term sequelae of their treatment is essential if we are to provide these children and young adults with as normal a life as possible. PMID- 8353667 TI - Acute tracheal obstruction. PMID- 8353668 TI - Appropriateness of cardiac surgery in the elderly. PMID- 8353669 TI - Occupational health and safety for doctors. PMID- 8353670 TI - Cardiac surgery in older people--the Papworth experience. PMID- 8353671 TI - Role of the respiratory nurse specialist. PMID- 8353672 TI - Writers' cramp. AB - At least 4000 people suffer from writers' cramp in the UK. While diagnosis is straightforward, treatment is difficult and many therapies are unsatisfactory. This article reviews the various manifestations of writers' cramp, the physiological evidence indicating that it is a neurological disease and the therapeutic techniques available. PMID- 8353673 TI - Computed tomography scanning of the thorax. AB - Although the chest radiograph remains the initial imaging study in patients with intrathoracic pathology, computed tomography has become useful in the early detection and evaluation of all aspects of lung, mediastinal, pleural and chest wall disease. High resolution computed tomography has particular advantages in the characterization of parenchymal lung disease. PMID- 8353674 TI - 'Pick's disease'--101 years on still there, but in need of reform. PMID- 8353675 TI - Fluoxetine in phantom limb pain. AB - Complete recovery of phantom limb pain of five years' duration occurred in a 71 year-old man following treatment with fluoxetine. There was no coexisting affective disorder. Further research is indicated in view of the postulated role of lowered central 5-hydroxytryptamine activity in the genesis and maintenance of chronic pain. PMID- 8353676 TI - Familial cosegregation of affective disorder and Hailey-Hailey disease. AB - We report on a family with co-occurrence of affective disorder and Hailey-Hailey disease in two brothers and the mother. The putative chromosomal locus of Hailey Hailey disease, which is a rare dominantly inherited dermatosis, may be a promising candidate region for genetic studies in affective disorder. PMID- 8353677 TI - Secondary prevention of non-fatal deliberate self-harm. The green card study. AB - In an attempt to address the low compliance with offers of treatment shown by patients after episodes of non-fatal deliberate self-harm (DSH), patients who had harmed themselves for the first time were offered rapid, easy access to on-call trainee psychiatrists in the event of further difficulties, and they were encouraged to seek help at an early stage should such problems arise. The follow up data obtained after one year showed a significant reduction of actual or seriously threatened DSH in the experimental group, who also made considerably less demands on medical and psychiatric services, when compared with controls. PMID- 8353678 TI - Thalamo-frontal psychosis. AB - A 43-year-old man presented with an 18-month history of acute-onset cyclical behavioural change affecting mood, appetite, sleep, and energy levels. This had followed an initial episode of transient drowsiness which lasted 24 hours. On examination, there was some evidence of visual memory and frontal lobe deficits. A brain CT scan showed bilateral thalamic infarcts and a brain SPECT scan showed bilateral hypoperfusion of the frontal lobes. To our knowledge, this is the first reported case of thalamic infarction associated with acute-onset cyclical affective psychosis with clinical and neurophysiological features of frontal lobe syndrome. The case also highlights the possible role of thalamo-frontal circuits in the pathogenesis of the Kleine-Levin syndrome. PMID- 8353679 TI - Tourette's syndrome and right hemisphere dysfunction. AB - Poor performances of patients with Tourette's syndrome (TS) on tests requiring visual-perceptual abilities had led previous authors to the suggestion of right hemisphere involvement. We have compared the results of neuropsychological examination of 16 children with TS, with those of 16 children with a lesion of the right hemisphere. No evidence was found of a dysfunction of the right hemisphere in TS. PMID- 8353680 TI - Oedipus at Delphi. PMID- 8353681 TI - Clozapine and negative symptoms. PMID- 8353682 TI - Salivary testosterone levels and major depressive illness in men. PMID- 8353683 TI - Attitudes to mental illness. PMID- 8353684 TI - An Eysenck for the 1990s? PMID- 8353685 TI - Integration of psychodynamics in Scandinavian psychiatry. PMID- 8353686 TI - Child psychiatric syndromes with a somatic presentation. PMID- 8353687 TI - Parental bonding. PMID- 8353688 TI - Tattooed female psychiatric patients. PMID- 8353689 TI - Postage stamp test for sexual disorders. PMID- 8353690 TI - Gastric emptying and bloating in anorexia nervosa. PMID- 8353691 TI - Blood-letting in bulimia nervosa. PMID- 8353692 TI - Abuse of the nasogastric tube in patients with eating disorders. PMID- 8353693 TI - Psychological treatment of generalised anxiety disorder. A review of the clinical significance of results in outcome studies since 1980. AB - Comparative outcome studies of generalised anxiety disorder suggest that psychological therapy is a potentially valuable alternative to anxiolytic medication. However, on average psychological therapy results in modest improvements in symptoms, with about 50% of patients achieving normal functioning. Limited follow-up data indicate that these changes are maintained over six months. Cognitive therapy appears to be most effective, although comparisons with other therapies are limited and non-specific factors are clearly important. There is also evidence of considerable variability in outcome between studies, with the best results obtained with patients who are free of anxiolytic medication and recruited directly from primary care or other non-psychiatric settings. The effects on outcome of patient characteristics known to be associated with more severe illness and complexity of clinical presentation have yet to be explored. A balanced appraisal of the value of psychological therapy with this common condition requires a fuller description of sample characteristics and more systematic investigation of the clinical significance of treatment effects over the long term. PMID- 8353694 TI - Alzheimer's disease and chromosome 14. Different gene, same process? PMID- 8353695 TI - A controlled study of the onset, duration and prevalence of postnatal depression. AB - In a two-stage screening procedure using the Edinburgh Postnatal Depression Scale and Goldberg's Standardised Psychiatric Interview, 232 women six months after delivery were compared with control women individually matched for age, marital status and number of children, obtained from general practitioner lists, who were not pregnant nor had had a baby in the previous 12 months. No significant difference in the point prevalence of depression at six months was found between the postnatal (9.1%) and control women (8.2%) nor in the six-month period prevalence (13.8% postnatal, 13.4% controls), but a threefold higher rate of onset of depression was found within five weeks of childbirth. The possible explanations relate to the long duration of depression in women with young children, and the stressful effect of childbirth and its psychosocial sequelae. PMID- 8353696 TI - A pilot study of schizophrenia-like psychosis in epilepsy using single-photon emission computerised tomography. AB - In a pilot study, SPECT was used to explore differences in rCBF between a group of patients with schizophrenia-like psychoses of epilepsy (SLPE) and a matched group of epileptic controls. Five patients in each group were investigated and those with SLPE showed significant reductions in the index of rCBF in the left medial temporal region. These differences are being investigated further. PMID- 8353697 TI - The relationship between social dysfunctioning and psychopathology among primary care attenders. AB - The extent of social dysfunctioning and its relationship to psychological disorders among Dutch primary care patients was examined. Social dysfunctioning in these patients was rather limited, but was more pronounced in patients with a psychological disorder than in those without. Disabilities were largely restricted to the occupational and social roles, with family role functioning and self-care relatively intact. Social dysfunctioning was moderately related to psychopathology, with higher levels of dysfunctioning in more severe and depressed cases. The extent of social dysfunctioning among patients with both anxiety and depression was similar to that of patients with a single diagnosis of depression. Depressed patients had a similar level of dysfunctioning to non psychotic psychiatric out-patients. Analyses regarding the effects of diagnosis and severity on social dysfunctioning revealed considerable overlap between these two aspects of psychopathology. This study supports the need for a simultaneous but separate assessment of psychopathology and social dysfunctioning. However, future research should incorporate additional predictors of social dysfunctioning (e.g. personality, life events, long-term difficulties, physical disorders), and prospective studies should be conducted to clarify the temporal sequences of symptom severity, diagnosis, and comorbidity on the one hand, and social dysfunctioning on the other. PMID- 8353698 TI - Suicide notes. AB - Detailed case reports of incidents of suicide and attempted suicide on the London Underground railway system between 1985 and 1989 were examined for the presence of suicide notes. The incidence of note-leaving was 15%. Notes provided little insight into the causes of suicide as subjectively perceived, or strategies for suicide prevention. PMID- 8353699 TI - A controlled trial of home-based acute psychiatric services. I: Clinical and social outcome. AB - While research has shown community-based psychiatric care to be as good as, or better than, hospital-based care, generalisation to clinical practice has been difficult. This prospective, randomised controlled study examined a community based approach feasible within NHS conditions. Ninety-four patients were randomly allocated to experimental and 78 to control treatments and followed for one year. The groups were well matched apart from an excess of psychotic control patients. No differences in clinical or social functioning outcome were found. Both groups improved substantially on clinical measures in the first six weeks, with some slow consolidation thereafter. There were three suicides in the control group and one in the experimental group. Access to care was better in the experimental group (93% attended assessment) than in the control group (75% attended assessment). PMID- 8353700 TI - A controlled trial of home-based acute psychiatric services. II: Treatment patterns and costs. AB - Treatment records of 94 patients treated in an experimental home-based psychiatric service and 78 control patients in standard care were collected over one year. There was a substantial reduction in in-patient care in the experimental group, both in terms of proportion admitted and duration of admissions, despite similar out-patient and general practice care. The total treatment costs were significantly larger (> 50%) for standard care when controlled for by diagnostic grouping. Costs were further examined by including all specialist psychiatric care, and by excluding patients with primary diagnoses of brain damage or alcoholism. Sensitivity analysis explored the effects of increasing the cost of home visits. The relative cost effectiveness of the experimental service persisted. Clinical and social outcome was similar in control and experimental groups. PMID- 8353701 TI - Befriending young mothers. AB - The context of voluntary befriending schemes to help mothers of young children is outlined. There is evidence that two main UK voluntary befriending schemes to help mothers of young children engage families where there is significant psychosocial morbidity. It is concluded that well conducted befriending schemes can make a significant contribution to the mental health of mothers and children. Whether they do so will depend on their experience and training and the elements they incorporate. PMID- 8353702 TI - The importance of the role of the patient in the outcome of schizophrenia. AB - The Family Interpersonal Perception Test (FIPT) was used to explore the relationships between schizophrenic patients and their parents, and how these related both to relapse in the year after discharge and to improvement in social functioning. Forty schizophrenic patients and their parents were tested during their first ever admission to hospital and again two years later. Parents' and patient's views of each other were more negative in those with worse outcome, but what most significantly distinguished groups with different outcomes was how patients expected their parents to see them. The FIPT, therefore, reveals patterns of interaction in which the patient's role in outcome is at least as important as that of the parents, and can aid the identification of specific features with which to work in therapy. PMID- 8353703 TI - Acting on delusions. I: Prevalence. AB - Associations between delusions and abnormal behaviour were retrospectively assessed in a sample of 83 consecutively admitted deluded subjects. All were interviewed about events in the previous month using a new measure of delusional phenomenology and action. For 59 subjects this information was supplemented by informant interviews. Clinical consensus was reached concerning the probability that actions reported by informants were linked to delusions. Half of the sample reported that they had acted at least once in accordance with their delusions. Violent behaviour in response to delusions was uncommon. Information provided by informants suggested that some aspect of the actions of half of the sample was either probably or definitely congruent with the content of their delusions. However, there was no link between self-reports and informants' reports of such action. A latent class analysis of self-reported delusional action suggested three classes of action, namely aggressive to self or other, defensive action, and either none or single action. Self-reported action was associated with delusions of catastrophe. Informant data suggested that persecutory delusions were the most likely to be acted upon, but in contrast delusions of guilt or catastrophe appeared to decrease the chance of delusional behaviour. Actions associated with abnormal beliefs are more common than has been suggested. PMID- 8353704 TI - Acting on delusions. II: The phenomenological correlates of acting on delusions. AB - The aim of the study was to identify the phenomenological characteristics of those delusions which are associated with action. The sample consisted of 79 patients admitted to a general psychiatric ward, each of whom described at least one delusional belief. The variables studied included the phenomenology of the delusions, and behaviour. Two behavioural ratings were used, one derived from the subjects' own description of their behaviour and the other from information provided by informants. There was no association between delusional phenomenology and acting on a delusion when the subjects' behaviour was described by informants. When action was described by the subjects themselves, acting was associated with: being aware of evidence which supported the belief and with having actively sought out such evidence; a tendency to reduce the conviction with which a belief was held when that belief was challenged; and with feeling sad, frightened or anxious as a consequence of the delusion. PMID- 8353705 TI - Depression in old age. A reconsideration of cerebral disease in relation to outcome. AB - In a prospective study, 32 patients with depressed mood and cerebral pathology were compared over one year with 66 depressed patients who were cerebrally intact. The hypothesis that the former would have a poorer outcome for depression was not confirmed, although the group with cerebral pathology had a significantly higher than expected death rate. Prognostic factors were identified only for the cerebrally intact group. Those who had major depression were more likely than those with minor depression to be given physical treatments, irrespective of which group they belonged to. PMID- 8353706 TI - Psychiatric morbidity and compulsory admission among UK-born Europeans, Afro Caribbeans and Asians in central Manchester. AB - Psychiatric admissions in Central Manchester of Europeans, Afro-Caribbeans, and Asians (within three age-bands) were studied over four years. Among the Afro Caribbean group there were more single or unemployed persons than in either the Asian or European groups, which suggested greater socio-economic disadvantage. Rates for first admissions and readmissions among Afro-Caribbeans were greater; among Asians they were similar except for the 16-29-year age-group, who tended to have lower rates than Europeans. A higher proportion of Afro-Caribbeans and Asians were psychotic. In the Afro-Caribbean group, the raised rates of admission were largely attributable to increased rates of schizophrenia. The highest rate occurred in second-generation (UK-born) Afro-Caribbeans and was nine times that among Europeans. The police were more frequently involved in the admissions of Afro-Caribbeans compared with Europeans or Asians. Higher proportions of Afro Caribbeans and Asians who were readmitted were detained under the Mental Health Act 1983, when compared with Europeans. PMID- 8353707 TI - Mirth, laughter and gelastic seizures. AB - Little is known about what pathways subserve mirth and its expression laughter. We present three patients with gelastic seizures and laughter elicited by electrical stimulation of the cortex who provide some insight into the mechanisms of laughter and its emotional concomitants. The first patient had seizures manifested by laughter without a subjective feeling of mirth. Magnetic resonance imaging showed a cavernous haemangioma in the left superior mesial frontal region. Ictal subdural electrode recording showed the seizure onset to be in the left anterior cingulate gyrus. Removal of the lesion and of the seizure focus rendered the patient virtually seizure free over 16 months of follow-up. The other two patients had complex partial seizures of temporal lobe origin. Electrical stimulation of the fusiform gyrus and parahippocampal gyrus produced bursts of laughter accompanied by a feeling of mirth. These cases reveal a high likelihood of cingulate and basal temporal cortex contribution to laughter and mirth in humans, and suggest the possibility that the anterior cingulate region is involved in the motor act of laughter, while the basal temporal cortex is involved in processing of laughter's emotional content in man. PMID- 8353708 TI - Reliability of histological diagnosis including grading in gliomas biopsied by image-guided stereotactic technique. AB - We report clinical and pathological data of 419 image-guided stereotactic biopsies. In the present series the diagnostic yield, estimated by comparing the original histological diagnoses with follow-up data, was found to be approximately 94% in gliomas. As it has been suggested that malignancy of astrocytic gliomas may be considerably underestimated in the small tissue samples obtained by stereotactic biopsy, we have reviewed 160 adult, diffuse supratentorial astrocytic tumours, correlating the original Kernohan tumour grades with survival. In this grading system, although there was generally a good correlation between histological grade and survival probability (P < 0.0001), no distinction could be made between the grade 3 (anaplastic astrocytoma) and grade 4 (glioblastoma) groups. Tumour grades obtained by applying the criteria of the more recent Daumas-Duport grading system were also determined and correlated with survival. These latter tumour grades not only correlated well with survival (P < 0.0001), but also enabled us to identify a group of patients with intermediate grade malignancy (grade 3, anaplastic astrocytoma), surviving longer than those with grade 4 tumours. Image-guided stereotactic biopsy is a useful means of providing tissue samples for histological diagnosis of brain neoplasms, including gliomas. Histological grading of adult, diffuse supratentorial astrocytic gliomas diagnosed by this technique is possible and should be carried out using an appropriate grading system. PMID- 8353709 TI - Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS. AB - The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age range 25-62 years), four of whom had a probable HIV-1 associated dementia complex, and six non-demented heterosexuals (four males and two females, age range 21-73 years). Ten males without a primary neurological or psychiatric disease served as a control group. The number of OXT-expressing neurons in the paraventricular nucleus of both groups of AIDS patients was approximately 40% lower than that of the controls. In contrast, the three groups showed no significant differences in the number of AVP-expressing neurons in the paraventricular nucleus. Since there were no significant differences in the number of AVP and OXT cells between the homosexual and heterosexual subjects with AIDS, the morphological difference in the paraventricular nucleus seems to be related to AIDS and not to sexual orientation. No inflammatory changes were found in the paraventricular nucleus area. The selective changes in the OXT neurons of the paraventricular nucleus may be the basis for part of the neuroendocrine, autonomic dysfunction or vegetative symptoms in AIDS. PMID- 8353710 TI - Brain MRI changes in phenylketonuria. Associations with dietary status. AB - Following the introduction 30 years ago of neonatal screening and early dietary treatment for phenylketonuria there has been a dramatic decrease in the severity of neurological dysfunction associated with this disorder. However, there is evidence that subtle neurological impairment remains common in early treated subjects and in the last 3 years there have been a number of reports of overt neurological impairment with white matter abnormalities on MRI. The frequency of white matter changes in phenylketonuria, and the relation of these changes to dietary management, have remained unclear. The present study examines MRI findings in 34 subjects aged 8-33 years. Twenty-five subjects had been detected by routine neonatal screening and nine had been missed in the screening programme. At the time of the investigation 16 of the early treated and two of the late treated subjects were still receiving a diet low in phenylalanine. All but two of the 34 subjects showed abnormalities on MRI. In the early diagnosed group it could be shown that the severity of MRI changes (graded 1-5) was significantly and independently associated with phenylalanine concentrations at the time of investigation and the time since dietary treatment had been withdrawn. These data are consistent with studies in animals showing that hyperphenylalaninaemia increases myelin turnover in a dose dependent manner. It is suggested that the effects of phenylalanine on myelin pose a lifelong hazard to the nervous system. PMID- 8353711 TI - The causalgia-dystonia syndrome. AB - We report 18 patients (16 women and two men) with causalgia and dystonia, triggered by peripheral injuries in 15 cases and occurring spontaneously in three. The injury was often trivial, and did not cause overt peripheral nerve lesions. The mean age at presentation was 28.5 years. None had a family history of dystonia. The leg was affected initially in 12 patients, the arm in the remaining six cases. All had burning pain, allodynia and hyperpathia, along with vasomotor, sudomotor and trophic changes. All developed dystonic muscle spasms in the affected part. Dystonia always appeared at the same time or after the causalgia. The spasms were typically sustained, producing a 'fixed' dystonic posture, in contrast to the mobile spasms characteristics of idiopathic torsion dystonia. There was spread of the causalgia and of the dystonia from its initial site both in the affected limb and to other extremities, the latter in hemiplegic, transverse and triplegic distribution. All investigations were normal. All modes of conventional treatment failed to relieve either the pain or the dystonia, but two patients recovered spontaneously. At present it is impossible to decide whether this distressing syndrome is a true functional disorder of the central nervous system, or is of psychogenic origin. PMID- 8353712 TI - Asymmetrical pre-synaptic and post-synpatic changes in the striatal dopamine projection in dopa naive parkinsonism. Diagnostic implications of the D2 receptor status. AB - Nine L-dopa na ve patients with clinically diagnosed parkinsonism were studied using positron emission tomography with 6-L-[18F]fluorodopa ([18F]dopa, a pre synaptic tracer) and [11C]raclopride (which binds to D2 receptors). Putamen [18F]dopa uptake was reduced in all patients, confirming a loss of function affecting the nigrostriatal projection. In eight patients the putamen with the lowest [18F]dopa uptake (always contralateral to the clinically most affected side) had the highest [11C]raclopride binding, suggesting upregulation of the post-synaptic D2 receptors. In the ninth patient [11C]raclopride binding was lower in the putamen with the lowest [18F]dopa uptake, indicating an additional post-synaptic deficit. All nine patients were shown to be L-dopa responsive. The subsequent clinical course of the former eight patients has been typical of idiopathic Parkinson's disease, whilst the ninth patient has developed postural hypotension, urinary incontinence and respiratory stridor typical of multiple system atrophy. Reduced [11C]raclopride binding in L-dopa naive parkinsonian patients might serve as a useful early marker of this condition. PMID- 8353713 TI - Response choice in Parkinson's disease. The effects of uncertainty and stimulus response compatibility. AB - Reaction time paradigms provide a set of methods for assessing aspects of the planning and execution of voluntary movements in Parkinson's disease. Attention has focused mainly on the issue of programming of responses, employing a combination of simple reaction time (SRT) and choice reaction time (CRT) paradigms. The first part of the present study replicated an earlier finding in which patients showed a disproportionate slowing in CRT compared with SRT. The main aim of the study was to investigate the possible role of response choice, a key stage prior to motor programming in this CRT deficit. Two factors were manipulated: (i) response uncertainty and (ii) stimulus-response compatibility. The patients showed a normal increase in reaction time with increasing uncertainty in the compatible conditions, and a normal response to stimulus response compatibility in the two-choice task. However, the two groups showed qualitatively different patterns of interaction between the two experimental factors, with only the patients showing a disproportionate slowing with incompatible stimulus-response relationships in the four-choice task. The data were interpreted in terms of Hasbroucq et al.'s (1990) list-rule model of stimulus-response compatibility effects, which suggested that the patients and controls were using different strategies for dealing with incompatible stimulus response relationships. The use of different strategies makes it impossible to determine whether or not the processing of the patients is impaired in Parkinson's disease, although further research is suggested to clarify the question. However, the present data suggest that any impairment in response choice is unlikely to contribute to the slowing in CRT in Parkinson's disease under conditions of high stimulus-response compatibility. PMID- 8353714 TI - Alternating fluency in Parkinson's disease. An evaluation of the attentional control theory of cognitive impairment. AB - One theory for the pattern of cognitive impairment associated with Parkinson's disease is that deficits are apparent only on tasks which rely on the internal control of attention, which in turn is assumed to place heavy demands on limited attentional resources. This theory is evaluated in the present study by examining the performance of Parkinson's disease subjects and matched healthy control subjects on a series of fluency tasks. In one condition, subjects were required to generate exemplars under standard verbal fluency instructions, i.e. either to a single letter or a single semantic category. In a related condition, subjects had to generate exemplars alternately using two fluency probes, which could either be from the same domain, i.e. letter-letter or category-category, or from different domains, i.e. category-letter. The requirement to alternate between fluency probes presumably places greater demands on internal attentional control mechanisms, and in a yoked condition, subjects were given external cue cards to minimize these extra demands. Overall, there was no evidence that Parkinson's disease subjects had a basic fluency deficit, nor were they impaired when required to alternate between probes of the same domain. A specific deficit did emerge, however, for the mixed alternating condition (i.e. category-letter), in which Parkinson's disease subjects produced significantly more perseverative errors and had a significantly lower output. The former of these was reversible by the provision of external cue cards, but the overall output was unchanged. These data do not support the theory of internal attentional control, at least as a general theory of cognitive impairment in Parkinson's disease. To explain the observed pattern, we propose that Parkinson's disease is associated with: (i) a deficit in inhibitory attentional processes, and (ii) an impairment in the maintenance of those internal representations which control action. PMID- 8353715 TI - Evidence of multiple memory systems in the human brain. A [18F]FDG PET metabolic study. AB - Patients with global amnesia of different aetiologies (n = 11), and patients with probable Alzheimer's disease of recent onset and mild to moderate severity (n = 18) underwent extensive neuropsychological examination, which included the evaluation of multiple components of memory, and a measurement of regional cerebral glucose metabolism with [18F]fluoro-deoxyglucose ([18F]FDG) and PET. In the neuropsychological tests, both global amnesia and Alzheimer's disease patients had impaired episodic long-term memory, while deficits of short-term, semantic and implicit memory were present only in Alzheimer's disease. When local metabolic rates for glucose were compared with values from age- and education matched normal controls, a common pattern of bilateral hypometabolism was present in the hippocampus, cingulate and frontal basal cortex of both global amnesia and Alzheimer's disease patients. On the other hand, significant hypometabolism was found in the thalamus in only global amnesia, and in the frontal, parietal and temporal associative cortex in only Alzheimer's disease. The results of a multivariate regression analysis of test scores with metabolic data indicated that different clusters of cerebral areas were associated with each of the main components of memory function. These data are in agreement with 'neural network' models of the neural basis of cognition, according to which complex functions are subserved by multiple interconnected cortical and subcortical structures. PMID- 8353716 TI - Autobiographical amnesia resulting from bilateral paramedian thalamic infarction. A case study in cognitive neurobiology. AB - A patient with a chronic amnesic state resulting from bilateral paramedian thalamic infarction showed a pattern of retrograde amnesia not previously reported. Personally relevant autobiographical memory was profoundly impaired, whereas knowledge of famous people and public events was relatively spared. Furthermore, knowledge of famous people, including the ability to make accurate temporal judgements, was less affected than knowledge of public events. In addition, we have documented a severe and systematic distortion of personal memory. These findings are not compatible with current accounts of retrograde amnesia based either upon the type of information stored (e.g. episodic versus semantic memory), or upon simple storage versus access models. We propose an explanation based upon an interactive cognitive model in which the patient shows a disorder at the 'thematic retrieval framework' level of memory organization due to a disconnection of frontal and medial temporal memory systems. PMID- 8353717 TI - Face perception after brain injury. Selective impairments affecting identity and expression. AB - Current theoretical models of face perception postulate separate routes for processing information needed in the recognition of a familiar face, for matching photographs of unfamiliar faces and for the analysis of facial expressions. The present study investigated this claim in a group of ex-servicemen who had sustained unilateral brain injuries affecting posterior areas of the left or right cerebral hemisphere. Care was taken to confirm the nature of impairment by using two different tasks to assess each of the three theoretically defined abilities (leading to a total of six tasks). We adopted a stringent application of the double dissociation methodology to investigate the pattern of performance across tasks of individual ex-servicemen. A selective impairment was defined as a significantly impoverished performance on both tests of a specific ability, while all other tasks were performed within normal limits. In addition, we used both accuracy and response latency measures to substantiate evidence for spared or defective abilities. The results showed selective impairments of all three abilities on accuracy scores. Response latency data confirmed the finding of a selective deficit in the processing of facial expressions, but produced evidence suggesting that impairments affecting familiar face recognition and unfamiliar face matching were not completely independent from each other in this group of ex servicemen. PMID- 8353718 TI - Deficit in classical conditioning in patients with cerebellar degeneration. AB - There is evidence from animal experiments that the cerebellum and its associated brainstem circuitry are involved in the acquisition of the conditioned response. In order to obtain evidence for their involvement in humans, we studied classical delay conditioning, using the eye-blink conditioned response, in five patients with pure cerebellar cortical atrophy and seven patients with olivopontocerebellar atrophy. The results were compared with those obtained in a group of neurologically healthy volunteers matched with the patients for age and sex. The two groups of patients had similar abnormalities in the acquisition of the conditioned response and produced fewer conditioned responses than in the control subjects in any given block of trials. Many of the patients' conditioned responses were inappropriately timed with respect to the conditioned stimulus. These results support the role of the cerebellum in the expression and timing of the conditioned response. PMID- 8353719 TI - Stretch-induced electromyographic activity and torque in spastic elbow muscles. Differential modulation of reflex activity in passive and active motor tasks. AB - Stretch-evoked electromyographic (EMG) activity and torque signals have been studied in elbow joint muscles of both sides of patients with spastic hemiparesis and healthy subjects. In order to reveal differences in the generation of muscle tone between clinical assessment and functional movement, stretches of different velocities and amplitudes were applied during passive and quasi-functional active motor tasks. In spastic patients the strength and duration of the EMG responses following stretching of flexor and extensor muscles during both passive and active tasks were dependent on the stretch velocity and duration, respectively. This effect was seen on both the spastic and unaffected side. Under passive conditions EMG activity after stretching was negligible in the limb muscles of healthy subjects, of small amplitude in unaffected limbs of the patients, but was strong in affected muscles. Under active conditions, the amplitude of the early (M1) component of the EMG signal was larger, while the later components (M2 and M3) were smaller. These differences were due more to a change in reflex gain than to a change in reflex threshold when the stretch velocity signal was the basis for calculation. It is suggested that in spastic paresis, modulation of stretch induced EMG activity in the spastic limb becomes restricted to a smaller range with a poor ability to switch off under passive conditions. Furthermore, the reflex EMG activity suffers a reduced facilitation under active conditions. In comparison with unaffected limbs the stretch-evoked torque on the affected side was increased under passive conditions (due to the extra EMG activity) and decreased under active conditions (due to a reduced EMG activity). An increased torque to EMG ratio was found in spastic flexor and extensor muscles during active tasks. This is thought to be due to changes in mechanical muscle fibre properties suffered as a consequence of defective muscle activation following cerebral lesions. The consequences for clinical assessment of muscle tone and therapy of spastic movement disorder are discussed. PMID- 8353720 TI - Colour vision in New World monkeys and the single-locus X-chromosome theory. AB - The single-locus X-chromosome theory was proposed to explain the unique intra- and inter-species variation in the colour vision found in New World monkeys. The colour vision of only five species of these monkeys has been studied in any detail, and although this data does show some minor deviations from the theory, it is generally consistent with the theory. It has been suggested that the colour vision of New World monkeys may represent an intermediate stage in between the dichromatic colour vision of non-primate mammals and the uniform trichromacy of Old World primates. Alternatively, the colour vision system of New World monkeys may represent a method of obtaining the maximum variation in the colour vision of closely related family groups. PMID- 8353721 TI - Topographic organization of the corticonuclear projections from the paraflocculus in the albino rat: an autoradiographic orthograde tracing study. AB - The topographic organization of corticonuclear projections from the paraflocculus was studied in rats by an autoradiographic orthograde tracing method. The corticonuclear fibers from the paraflocculus terminated primarily in the caudoventral part of the lateral cerebellar nucleus and in the lateral part of the posterior interpositus nucleus. The rostrolateral part of the ventral paraflocculus projected only to the lateral nucleus, and the caudomedial part projected only to the posterior interpositus nucleus. Although differential projections from the dorsal and ventral paraflocculi were not clearly observed, the dorsal paraflocculus appeared to project to slightly more dorsal parts of the lateral and posterior interpositus nuclei than did the ventral paraflocculus. The lateral, medial, rostral, and caudal parts of each sublobule tended to project to the ventral, dorsal, rostral, and caudal regions within the caudoventral part of the lateral nucleus, respectively, despite massive overlap in the individual terminal fields. The corticonuclear projection from the dorsal and ventral paraflocculi to the posterior interpositus nucleus were organized in different directions; those from the dorsal paraflocculus were organized rostrocaudally, while those from the ventral paraflocculus were organized mediolaterally. These results suggest that in rats the corticonuclear projections from the paraflocculus are topographically organized in the mediolateral and rostrocaudal directions as well as in the dorsoventral direction. PMID- 8353722 TI - Reversed phase HPLC analysis of proenkephalin-related and prodynorphin-related end-products in the brain of a urodele amphibian, Ambystoma tigrinum. AB - Acid extracts of the brain of a urodele amphibian, Ambystoma tigrinum, were screened with radioimmunoassays specific for enkephalin-related products and dynorphin-related products. Following Sephadex G-50 column chromatography a peak of enkephalin-sized immunoreactive material was detected near the total volume of the column. The enkephalin-sized immunoreactivity was further analyzed by reversed phase HPLC. This analysis detected peaks of authentic Met-enkephalin and Leu-enkephalin. However, the molar ratio of Met-enkephalin to Leu-enkephalin in the brain of this amphibian was approximately 80:1. These observations would suggest that the Leu-enkephalin detected in the brain of Ambystoma may be derived from a source other than the Proenkephalin precursor. Neither Met-enkephalin-RGL or Met-enkephalin-RF were detected by radioimmunoassay in brain extracts from this urodele. However, following digestion with trypsin and carboxypeptidase B, a novel peak of C-terminally extended Met-enkephalin was detected. Two peaks of Prodynorphin-related products were also detected following gel filtration chromatography. These immunoreactive forms were detected using antisera specific for alpha-neo-endorphin and dynorphin B(1-13). No immunoreactive forms with antigenic determinants similar to mammalian dynorphin A(1-17) or dynorphin A(1-8) were detected in this species. Reversed phase HPLC analysis indicated that the major form of urodele alpha-neo-endorphin eluted with the same retention time as synthetic mammalian alpha-neo-endorphin. Urodele dynorphin B(1-13)-related immunoreactivity eluted as a single peak, however, this form did not elute with the same retention time as synthetic mammalian dynorphin B(1-13).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353723 TI - The visual system of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi). I. Retina. AB - The retina and choriocapillaris of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi), was examined at the light and electron microscopic levels. The inner limiting membrane is covered by an extensive system of vitreal blood vessels emanating from the hyaloid artery, which enters the eye ventrally at the proximal end of the elongated optic nerve head. Two size classes of ganglion cell soma are segregated by optic axon fascicles and Muller cell endfeet, all of which lie at the level of the ganglion cell layer. A third class of 'displaced' ganglion cells lies at the border of the inner plexiform and inner nuclear layers amidst tightly packed amacrine, bipolar and Muller cell soma. Two layers of horizontal cells lie vitread of a synaptic zone consisting of a complex arrangement of horizontal and bipolar dendrites invaginating rod spherules and cone pedicles to form single and multiple (three to six) synaptic ribbon connections, respectively. Immediately vitread of the photoreceptor nuclei lie a population of 'displaced' bipolars. Three types of photoreceptors are characterised: unequal double cones, single cones (large and small) and rods. These show retinomotor movements where the rods elongate in the light and are masked by the pigment epithelium and contract in the dark as the pigment migrates sclerad. Ultrastructurally, 4 types of dark-staining (osmophilic) granules are described: (1) Small glycogen granules (0.033 microns) aggregated at the bases of the photoreceptor nuclei and larger similar granules (0.078 microns and termed paraboloids) vitread to the ellipsoid; (2) tapetal granules (0.32 microns) distributed throughout the dorsal four-fifths of the retinal pigment epithelium (RPE); (3) pigment granules (0.5-2.0 microns) in the RPE, concentrated in ventral retina; (4) granules or melanosomes (0.813 microns) of the choriocapillaris. The second class of granules constitute a tapetum lucidum eliciting a yellow eyeshine when viewed in the dark. Two other tapeta also exist, a guanine tapetum (irregular guanine crystals) and a tapetum fibrosum (stacks of collagen fibrils). Functional correlations are made, and the putative ancestral (primitive) condition of particular visual characters is established for the ray-finned fishes by out-group comparisons. PMID- 8353724 TI - The visual system of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi). II. Cornea and lens. AB - The cornea of the Florida gar, Lepisosteus platyrhincus (Ginglymodi) was examined at the scanning and transmission electron microscopic levels. In addition, the schematic eye of the garfish was revealed by frozen sectioning of the whole orbit in the horizontal and transverse planes. The lens is spherical, obeys Matthiessen's ratio, and is supported by a dorsal suspensory ligament and a ventral retractor lentis muscle. The cornea, devoid of a spectacle, is comprised anteriorly of an epithelium (eight to ten cells thick) and covered by a layer of flattened cells up to 26 microns in diameter. On the scanning electron microscope, these cells appear to be covered in microplicae and microvilli. Beneath the epithelium lies a granular basement membrane abutting a true Bowman's layer, composed of a random arrangement of collagen fibrils with no keratocytes. The corneal stroma constitutes 54% of the total thickness and contains 55-65 collagen fibril lamellae, oriented perpendicular to neighbouring lamellae. Scattered keratocytes, containing large amounts of mitochondria, lipid droplets and glycogen granules lie in between the perpendicularly oriented lamellae. Posterior to the stroma is a thin and partially broken basement membrane (no true Descemet's membrane exists), adjacent to a monolayered endothelium covered in microvilli. In the periphery, an autochthonous layer is found between the stroma and the endothelium. Stromal pigment granules, enveloped in large nucleated cells, act as a non-occlusible yellow filter in the dorsal cornea. Functional correlations are made and the presence and/or thickness of corneal structures discussed in relation to the evolution of the vertebrate cornea. PMID- 8353725 TI - Anticipatory tonal coarticulation in Thai noun compounds after unilateral brain damage. AB - The time course and extent of anticipatory coarticulation between tones was investigated in normal and brain-damaged Thai-speaking subjects. Subjects were classified into five groups including 11 young normal, 9 old normal, 12 right hemisphere, 9 left hemisphere fluent, and 6 left hemisphere nonfluent. Stimuli consisted of five bisyllabic noun compounds with a falling tone on the initial syllable and each of the five Thai tones (mid, low, falling, high, rising) on the final syllable. Height and slope of F0 was measured at 10% intervals throughout the duration of the initial syllable. Results indicated anticipatory effects on both height and slope of the falling tone. Height effects extended throughout from the beginning. The falling tone was generally higher when occurring before the low/rising tones than when occurring before the mid/falling/high tones. Slope effects were restricted to the terminal portion. The falling tone before low/rising tones exhibited a steeper slope than before falling/high tones. In magnitude of effect, patients with left and right hemisphere lesions were statistically indistinguishable from those of normal subjects. No differences were noted in coarticulatory patterns as a function of aphasia type. All brain damaged speakers were more variable in F0 production than normals. Findings are interpreted to highlight properties of nonfluent aphasic speech and neurological bases of speech production. PMID- 8353726 TI - Broca on cerebral control for speech in right-handers and left-handers: a note on translation and some further comments. AB - In my analysis (Harris, 1991) of Broca's views (1865) on the relationship of handedness to speech representation, a passage from one of Broca's later articles was mistranslated. This has implications for one part of the analysis, which this note explains. New details and comments are also added to the story. PMID- 8353727 TI - Levy-Reid hypothesis. AB - The inconsistencies in the research findings looking to test for the Levy-Reid hypothesis on the relationship between hand posture and laterality have been accounted for in various ways. Some authors (Cohen, 1991; Weber and Bradshaw, 1981) have suggested that existing methodologies for experimentally establishing laterality of language functioning are unreliable. To overcome this constraint, we have taken Halsey, Blauenstein, Wilson, and Wills' (1980) suggestion of using cerebrovascular accident (CVA) patients in which laterality of expressive speech has been established incontrovertibly. We examined 74 CVA subjects assessing hand posture, handedness, and side of stroke. Our findings lend support for Levy-Reid, nevertheless further examination of the hypothesis using a cross-cultural sample underscores the impact education and culture have on hand posture. PMID- 8353728 TI - Locative prepositional phrases in severe aphasia. AB - Six severely aphasic patients were trained on C-VIC, a computerized alternative communication system. Patients with both global and Broca's aphasia were able to produce and comprehend locative prepositions using C-VIC. The Broca's aphasic patients were able to produce and interpret symbol order correctly in C-VIC locative prepositional phrases, despite their difficulties in performing the same tasks using English. One patient's verbal production of locative prepositional phrases improved markedly after C-VIC training. These results suggest that the "mapping" impairment suffered by some Broca's aphasics may be ameliorated by use of alternative communication system, such as C-VIC. PMID- 8353729 TI - Dysprosody following acquired neurogenic impairment. AB - Dysprosody is typically associated with the dysarthrias following acquired neurogenic disturbance but it has also been associated with impairment to the cortex of the right cerebral hemisphere (Behrens, 1985). Currently there is little agreement in the clinical literature as to the locus or nature of processes involved in production and reception of prosody. This paper investigates the usefulness of two psycholinguistic models of prosody--involving "abstract" and "concrete" processes (Ladd & Cutler, 1983)--in accounting for dysprosody following motor pathway as well as cortical lesions. Four groups of 10 adult patients each participated in the study; the first group had sustained a right cerebral hemisphere cortical stroke, the second group had hypokinetic dysarthria, the third group had ataxic dysarthria, and the fourth group was normal controls. Acoustic analysis using the Kay VisiPitch/PC was conducted on pairs of matched noun phrase and noun compounds (e.g., greenhouse, green house), interrogative and declarative versions of sentences, and sentences spoken in each of four different emotional tones. Right cerebral hemisphere damaged subjects produced shorter durations than the other groups for each stimulus class. However, all of the subjects were able to use duration to signal temporal information for the lexical distinction between noun compounds and noun phrases. The results are consistent with a model of prosodic control which involves both cortical as well as physiological control processes. Current treatment for dysprosody is discussed in light of this new emphasis on cognitive control processes. PMID- 8353730 TI - The Gogi (word-meaning) syndrome with impaired kanji processing: alexia with agraphia. AB - Two cases, one with probable Pick's disease and one with herpes simplex encephalitis, are presented, focusing on Gogi (word-meaning) aphasia-like syndrome as their salient clinical feature. Their aphasic symptoms were characterized by impaired kanji processing and preserved kana processing in writing and oral reading known as a defining feature of Gogi aphasia, but little evidence of so-called "phonetic use of kanji in writing" and "confusion between on- and kun-readings of kanji in oral reading" often observed in Gogi aphasia. Systematic neuropsychological test batteries administered to them showed that the selective impairment of kanji processing did not always arise from a disturbance of a specific ability known to be essential to Gogi aphasia (i.e., failure in comprehending the semantic content of spoken and written language), but rather from an amnestic disruption in the ability to access the correct orthographic and phonological forms of kanji words. This selective impairment of kanji processing may be compatible with "alexia with agraphia of kanji," recently known to be attributable to left posterotemporal lesions. These results suggest that Gogi aphasia (or similar syndromes) is not necessarily a real syndrome but a polytypic constellation of symptoms. PMID- 8353731 TI - Language and task effects on lateralized word recognition. AB - Behavioral laterality effects in naming and lexical decision in Farsi and English were used to evaluate three theories of cross-linguistic differences. First, the Scanning hypothesis predicts a smaller right visual hemifield advantage (RVFA) in Farsi in both tasks. Second, the Cerebral Dominance hypothesis predicts a consistent RVFA in both languages. Third, the Right Hemisphere hypothesis predicts a selective decrease in RVFA in Farsi for those components of the task that involve lexical semantic access. Results supported the Right Hemisphere hypothesis, showing greater right hemisphere contribution to orthographic addressing in Farsi than in English. PMID- 8353732 TI - The noun-verb problem and Chinese aphasia: comments on Bates et al. (1991). PMID- 8353733 TI - Where is the boundary between compounds and phrases in Chinese? A reply to Zhou et al. PMID- 8353734 TI - [Biochemical parameters in the blood in patients during open-heart surgery. II. Malondialdehyde, superoxide dismutase and catalase as indicators of formation and elimination of free oxygen radicals]. AB - Investigation of cardiosurgical patients have provided evidence for the generation of free oxygen radicals during open heart surgery. The finding of increased plasma malondialdehyde concentrations, considered to be an indicator of lipid peroxidation in cell membranes, is suggestive of this process. Simultaneously, the antiradical capacity of tissue was found to exhibit a decreasing trend, as established by the levels of superoxide dismutase and catalase in erythrocytes of peripheral blood which tended to diminish. The funding that no changes in the studied parameters were observed in the blood from the coronary sinus taken before and after interruption of coronary blood flow demonstrates that the commonly applied protection of the myocardium by hypothermic cardioplegic solution and topical cooling of the heart is effective in suppressing radical formation. (Fig. 5, Ref. 36.) PMID- 8353735 TI - [The effect of middle-molecular ninhydrin-positive substances isolated from the rat myocardium on rat serum arylamidase activity after administration of ethanol]. AB - Protein-free extract from the myocardium of control rats and the majority of its fractions were found to stimulate arylamidase activity. Ethanol administration to rats for 1, 3 or 7 weeks increased the amount of fractions which displayed an inhibitory effect. The observed changes were probably due to enhanced protein degradation and/or to decreased amino acid incorporation into proteins following ethanol administration. (Tab. 4, Fig. 2, Ref. 19.). PMID- 8353736 TI - [Treatment of ulcerative colitis]. AB - The authors' 10-year experience with the treatment of 134 patients suffering from ulcerative colitis is presented. The standard with sulfasalazine proved successful in mild forms of the disease, yet preparations containing only 5 aminosalicylic acid had to be administered to patients with intermediate and serious forms of the disease. The authors recommend to individualize treatment with corticoids and antibiotics and to reserve this approach for severe conditions. The use of supplementary therapeutic procedures, particularly administration of drugs affecting the immune system, is still a rather controversial issue. (Tab. 3, Ref. 24). PMID- 8353737 TI - [Celiprolol increases the microcirculation in subcutaneous tissue and calf muscles in essential hypertension]. AB - The microcirculation of the subcutaneous tissue and muscles of the extremities is changed already in the early stage of essential hypertension. Insight into the effect of celiprolol, a beta blocker of the third generation, on tissue microcirculation is of both pathogenetic and therapeutic value. On using the method of Na131I tissue clearance, the effect of celiprolol on the microcirculation of subcutaneous tissue and muscles of the extremities was studied in 21 patients with essential hypertension. Celiprolol was administered orally in the daily dose of 300 mg. After one-week administration celiprolol significantly reduced mean arterial pressure and significantly increased the microcirculation in the subcutaneous tissue of the hand and crus as well as in the calf muscle. Celiprolol was thus found to increase the microcirculation in those tissues of the extremities in which its decrease was recorded before onset of the treatment. The obtained results may be of therapeutic value particularly in patients suffering from ischemia of the lower extremities. (Fig. 2, Ref. 19.). PMID- 8353738 TI - [Electron microscopy immunolocalization of ribosomal ribonucleoproteins using autoantibodies from patients with systemic lupus erythematosus]. AB - Serum of patients against rRNP was tested by Western blot method. Four ribonucleoproteins (15, 16, 36 and 38 kDa) specifically reacted with the antiserum used. The autoantibodies were used for immunolocalization of antigenic structures by immunogold method on ultrathin cryosections of hepatocytes, cumulus cells of antral follicle and spermatocytes. Mice and hamsters were used. The cytoplasm appeared to be labelled most intensively. Gold particles were loosely arranged in the cytoplasm (cumulus cells) or they were associated with endoplasmatic reticulum (hepatocytes). Nucleoli were labelled by a lower incidence of the marker. Gold particles were found over the dense fibrillar component bordering on the granular component. In the cytoplasm individual gold particles were observed. (Fig. 7, Ref. 31.). PMID- 8353739 TI - [Catecholamines and changes in blood pressure during stress tests in type 1 diabetics]. AB - The influence of metabolic control on catecholamine secretion and blood pressure during upright posture, mental stress and physical exercise was studied in 34 normotensive normoalbuminuric type 1 (insulin-dependent) diabetic patients without autonomic neuropathy. A poor metabolic control did not induce different changes in blood pressure and plasma catecholamines as compared to a good metabolic control, except for an exaggerated rise in plasma adrenaline in patients with asymptomatic hypoglycemia. The lack of correlation between plasma catecholamines and blood pressure suggest that some other factors are also involved in the hemodynamic reaction to mental stress and physical exercise in diabetic patients. (Fig. 2, Tab. 3, Ref. 25.). PMID- 8353740 TI - [Immunotherapeutic principles in the treatment of tumors]. AB - Numerous clinical and experimental immunological studies have shown that the activity of the immune system plays a decisive role in the course of tumor-macro organism interaction. The aim of the present paper was to characterize the basic principles which should be taken into consideration in the complex strategy of cancer management. The best therapeutic effect can be achieved when the immune system is changed from the state of tumor-protective activity into tumor destructive activity. This can be achieved by the combined effect of three synergistic procedures: (1) elimination of the suppressive influence of tumor cells on the immune system; (2) elimination of the suppressive activity of the immune system; (3) stimulation of anti-tumor effector cell populations of the immune system. (Ref. 53.) PMID- 8353741 TI - [Time delay in acute myocardial infarct]. AB - The authors present their experience concerning the time-delay in 357 patients with acute myocardial infarction admitted to the coronary unit over the years 1988-1991. This time indicator was evaluated by using two approaches, i.e. the global time-delay (the time between the onset of the patient's complaints and his/her admission to the coronary unit) and patient's time-delay (the time between the onset of the patient's complaints and his/her decision to notify the health care service). Arbitrary criteria were set up: 10 hours for the former and 5 hours for the latter parameter. The established criteria were met by 40% of the patients. Only 24% of the patients presented at the coronary unit within 6 hours, and these could receive thrombolytic treatment. The decision time (patient's time delay) amounted that the education level of our population has to be enhanced so as to increase the number of patients with acute myocardial infarction presenting at the coronary unit at an early stage. (Tab. 1, Ref. 9.) PMID- 8353742 TI - [Incidence of malignant tumors in Slovakia. I. Levels and trends 1968-1989]. AB - In the period from 1968-1989 an increase in the overall incidence of malignant tumors was recorded in men. Of the individual localizations a particularly marked increase was recorded in tumors of the lung, followed by tumors of the oral cavity, pharynx, esophagus, pancreas, urinary bladder, kidney (related to smoking), as well as of the testis and prostate gland. In women the values of overall incidence were lower and the trends were relatively stabilized. This is due to the relatively slow increase in the incidence in cancer of the breast and female reproductive organs and to the slight increase in cancer of the lung. Cancer of the kidney, urinary bladder and pancreas exhibited increased incidence. Low values, stabilized and even decreasing trends were recorded in the incidence of cancer of the oral cavity, pharynx, esophagus, and larynx, as compared to values found in men. In both sexes the incidence of cancer of the stomach showed a pronounced decrease, while the incidence of cancer of the colon and rectum was increasing. A smaller or greater rise was found also in the incidence of tumors of the hematopoietic and lymphatic tissues (except Hodgkins's disease). The trends observed in the incidence of malignant tumors in Slovakia are suggestive of their uncontrolled course, not affected by preventive measures. Yet the findings provide important information for directing the measures so as to aim at localizations of priority. (Tab. 2, Fig. 7, Ref. 20.) PMID- 8353743 TI - [Transesophageal atrial pacing in bradyarrhythmia disorders of heart rhythm (preliminary report)]. AB - The aim of the paper was to assess the contribution of transesophageal atrial stimulation in bradyarrhythmic derangements of the heart rhythm. The main purpose was to make the diagnostic simpler and safer. Since the series of patients involved is small, our results are to be considered as a preliminary report. (1) When only dysfunction of the sinoatrial node is involved, the method yields results comparable to those obtained by invasive electrophysiological examination. Compared to the latter, invasive approach, the great advantage of the presented method is its repeatability and simplicity. (2) Greater caution is required on evaluating the conductivity, as it can not be reliably determined in the His-Purkinje system. (Tab. 2, Fig. 5, Ref. 12.) PMID- 8353744 TI - [The importance of terminology in education, professional activities and in research]. PMID- 8353745 TI - [Molecular medicine]. AB - The introduction of new methods into medicine, such as recombinant DNA, production of monoclonal antibodies, and particularly polymerase chain reactions, yielded much knowledge and information in fields like preventive medicine (prenatal screening), reproduction strategies (preimplantation diagnosis of genetic defects), molecular diagnosis (oncological and infectious diseases), gene therapy, etc. In many areas the practical use of these sophisticated approaches has become technically feasible yet due to the high cost involved it is still limited. The introduction of some screening programs will be associated with ethical problems of serious impact. To date we can already establish presymptomatic diagnosis of some progressive diseases for which however no therapy is available. Potential abuse of confidential genetic information as well as the possibilities of using gene therapy for "corrective eugenics" are loaded with serious ethical problems. Prospective doctors have to be prepared for this situation in the course of undergraduate studies of medicine. (Ref. 11.) PMID- 8353746 TI - [Antioxidative properties of cardioactive agents]. AB - Calcium entry blockers reduce the ischemia-reperfusion induced damage to the myocardium. Free oxygen radicals play a role in the pathogenesis of this injury. The mechanism of the protective action of calcium entry blockers is unknown in these conditions and appears to be independent of the blockade of slow calcium channels. As demonstrated in this paper, the calcium entry blockers nifedipine, verapamil and diltiazem are effective scavengers of free oxygen radicals and this characteristic may be importantly involved in their protective effect against myocardial damage induced by ischemia and reperfusion. The pro-oxidative capacity of the antineoplastic drug cisplatin is assumed to play a role in the mechanism of its renal toxicity action. The presented study showed that the new antioxidative substance with antiarrhythmic and antihypoxic properties-stobadine succeeded in inhibiting the pro-oxidative effect of cisplatin. Our findings suggest that administration of cisplatin along with antioxidants may result in a protective effect against the renal toxicity of cisplatin. (Fig. 5, Ref. 38.) PMID- 8353747 TI - [Diagnosis of echinococcosis in the population of Slovakia]. AB - Serologically diagnosed cases of echinococcosis in man occurring over the years 1970-1990 are reported. In the given period 292 serum samples were examined obtained from patients clinically suspected of echinococcosis, either with or without indication of localization in different organs. Of the total of 22 serologically positive patients echinococcal cysts were found in the liver in 17 patients (77.27%), in the lungs in three (13.63%) and in two patients the localization was not established. The patients with positive serological finding were within the age range of 33 to 68 years, with the exception of one 11-year old boy. The value of serological examination of echinococcosis in the subjects involved in our study is highlighted by the findings in those patients who underwent surgery. Both the positive and the negative serological results were confirmed by the surgical findings of the presence or absence of echinococcus. (Tab. 3, Ref. 22.) PMID- 8353748 TI - [The effect of ethanol on the occurrence of peptides with antibacterial effects in the rat myocardium]]. AB - The effect of 7% ethanol on the peptide content in the myocardium was studied during prolonged exposition. The protein-free extract from the myocardium of controls as well as experimental groups following 1-8 weeks ethanol administration contained peptides with antibacterial activity. Long-term ethanol administration resulted in changes in physico-chemical properties of peptides both compared with controls and also among the experimental groups mutually. The changes were manifested by differences in the elution profiles following gel chromatography and RF values after electrophoresis or by different amino acid composition. The results are compared with the influence of peptides on the growth of bacterial cultures S. aureus. Ethanol administration induced diminution of the diameter of the inhibitory zones. This effect was most marked in the group fed with ethanol for 3 and 8 weeks. (Fig. 5, Ref. 17.) PMID- 8353749 TI - [Does short-term high-frequency jet ventilation damage the tracheobronchial mucosa?]. AB - In anesthetized rabbits, the occurrence of histopathological changes was studied above below and the level of the endotracheal tube opening after one-hour high frequency jet ventilation (f = 150.min-1,Pin = 70-90 kPa, Ti = 0.5) with nonhumidified air and oxygen mixture (FiO2 = 0.6). The findings were compared with those obtained in intact rabbits and in rabbits which were inhaling nonhumidified air from the environment spontaneously via the endotracheal tube. Mechanical obstruction of the airways by mucus or necrosis of the mucous membrane was not observed. The major histopathological changes characteristic of inflammation and mechanical damage of the mucosa were recorded above the opening of the endotracheal tube. Towards the main bronchi the degree of the injury was decreasing. (Tab. 2, Fig. 2, Ref. 11.) PMID- 8353750 TI - [Serodiagnosis of larval toxocariasis in Slovakia]. AB - The results of serological examinations performed over the years 1986 to 1990 in patients suspected of larval toxocariasis, coming from different Institutes of National Health in Slovakia, are reported. Seropositivity was within the range from 9.38 to 23.56%. The five-year average was 17.72%, with a predominance of seropositivity in the country. Age-related analysis of the series of patients did not show any significant difference of seropositivity in children and adults (18.00 and 17.21% respectively). Higher seropositivity rates were found in boys (20.73%) compared to girls (14.69%). This was found to be reversed in adults, where women had higher seropositivity rates than men (20.61 and 12.08% respectively). The ocular for of larval toxocariasis showed a higher prevalence in adults. (Tab. 4, Fig. 1, Ref. 18.) PMID- 8353751 TI - [Changes in hemostasis in ischemic heart disease]. AB - The relationship between changes in blood coagulation, the occurrence and severity of risk factors of ischemic heart disease and the clinical condition of the patient was investigated. The at risk group of patients 42.2% had more than 3 pathological parameters. Intravascular blood coagulation was not activated in any of the patients. In patients with acute myocardial infarction (MI), 62.2% had more than 3 pathological parameters on the first day of MI development. Demonstrable activation of intravascular blood coagulation was found in 28.2% of these patients. On day 5 of MI, activation of intravascular blood coagulation was recorded in 57.7% of the patients treated by classical approach and in 15.4-30.8% of the patients on thrombolytic treatment. In the at risk group, primary hemostasis and the fibrinolytic system were more affected, in patients with MI the whole hemostatic mechanism was involved. On day 5 of MI, in patients with classical therapy pathological laboratory findings still persisted or were even more deteriorated, particularly increases in fibrinogen level. At that time, in patients on thrombolytic therapy no substantial changes of initial values were recorded. No correlation was found to exist between changes in hemostasis and the risk profile or between changes in hemostasis and the clinical severity of MI. The obtained results justify the administration of antithrombotic substances, especially in patients with unstable angina pectoris. On observing time constraints, administration of thrombolytics is justified in MI. (Fig. 9, Ref. 25.) PMID- 8353752 TI - [Long-term results of revascularization surgery in oblitertive arteriosclerosis of the lower extremities]. AB - The authors evaluated their 15-year experience with revascularization operations for atherosclerosis obliterans (ASO) of the lower extremities. Over the period from 1975 to 1990, 1112 patients with ASO were admitted to their department and in 674 (60.6%) of them revascularization operation was performed. Direct revascularization surgery (bypass, desobliteration, angioplasty) was performed in 318 (47.2%) patients and indirect revascularization, sympathectomy in 326 (52.8%) patients. On evaluating the long-term results of aortobifemoral (AF2), femoropopliteal (FP) and femorocrural (FC) bypasses the following long-term patency was established: AF2 bypass--patency up to 2 years 92%, up to 5 years 90%, up to 10 years 76%, up to 15 years 75%; FP bypass--patency up to 2 years 90%, up to 5 years 84%, up to 10 years 62%, up to 15 years 46%; FC bypass- patency up to 2 years 63%, up to 5 years 50%, up to 10 years 25%. Complications developed in 10%, the mortality rate was 2.5% and 8% in FP and AF2, respectively. The obtained results are comparable with the data published in the literature. The authors achieved the best results in the suprainguinal region with AF2 bypasses on using mostly dacron prostheses and in the infrainguinal region FP bypasses on using the autologous great saphenous vein. (Tab. 3, Fig. 4, Ref. 17.) PMID- 8353753 TI - [Quantitative changes in the ultrastructure of myocardial cells in Japanese quail during hypergravity, hypodynamia and space flight]. AB - The experimental work aimed at the quantitative ultrastructure of the myocardial cells of the Japanese quail Coturnix coturnix japonica during hypergravitation, hypodynamism and space flight in a Soviet satellite. For the determination of quantitative changes of the myocardial ultrastructure a morphometrical method was used with parameters like the number of mitochondria, average mitochondrial size, relative mitochondrial volume, deficiency of cristae and relative volume of myofibrils. The quails were observed in 3 groups. The absolute control consisted of quails living in normal Earth conditions, in the laboratory group the quails were exposed to conditions of hypergravitation and hypodynamism in a specially constructed centrifuge, and in the flying group the quails were exposed to space flight in a Soviet orbital station MIR. In the group of absolute controls no pathological changes of the myocardial ultrastructure were found. In the flying group there were no significant changes, with the exception of decreased relative volume of myofibrils, which however agrees with the findings on symptoms corresponding to human and animal heart weakness during space flights. In the laboratory group, pathological changes were observed in each of the fractions. The most significant pathological findings were found in the group controls in the center and in hypergravitation combined with hypodynamism. It can be concluded that the laboratories can simulate conditions induced by the start and flight of space ships. (Fig. 2, Ref, 8.) PMID- 8353754 TI - [Evaluation of hepatic damage in personnel in the anesthesiology- resuscitation department in relation to halothane exposure]. AB - In a simple uncontrolled toxicological study 27 workers of an anesthesiology resuscitation department of a hospital type III were examined. Besides detailed clinical examination, determination of basic hematological and biochemical parameters as well as ultrasonography, also selected parameters of proteosynthetic function of the liver, some so-called proteins of the acute phase and the biological half-life of antipyrine were established in the workers under study. The occurrence of pathological findings in the picture of the examinations performed was related to long-term professional exposure to halothane over the period of one year before the examination. With regard to the possibility of chronic hepatotoxic damage, appropriate attention should be paid to workers of anesthesiology-resuscitation departments, concerning particularly entrance medical examinations and regular screening and follow-up of their health condition, including check-ups hepatic parameters. (Tab. 4, Ref. 23.) PMID- 8353755 TI - [Morphologic findings in models of acute experimental pancreatitis]. AB - Morphological changes found in two models of acute experimental pancreatitis are presented. Acute pancreatitis was induced in rats by the method of ligation of the lateral pancreatic ducts and by the method of the blind duodenal loop. After four hours the animals were sacrificed and processed for light and electron microscopic examination. Changes indicative of edematous and necrotizing pancreatitis were recorded. In the electron microscopic picture the predominant findings were disintegration of organelles of acinar cells and the appearance of numerous vacuoles and autophagosomes. The presented models of pancreatitis are considered to be suitable for further research into the pathogenesis and therapeutic intervention of acute pancreatitis in rats. (Fig. 15, Ref. 8.) PMID- 8353756 TI - [Personal experience with endoscopic therapy of chronic pancreatitis]. AB - Endoscopic drainage is a modern and effective therapy in patients with chronic obstructive pancreatitis. The authors demonstrate their experience with this therapy in 20 patients. It resulted in pain disappearance in 60% of the patients and in body weight increase within 1 year after therapy in 55% of the patients. Steatorrhea was not significantly influenced by the therapy. The main complication of endoscopic therapy were frequent restenoses (30%). (Tab. 4, Fig. 2, Ref. 12.) PMID- 8353757 TI - [Biochemical indicators in the blood and liver in rats after administration of beta-escin]. AB - The effect of beta-escin on selected parameters of carbohydrate and lipid metabolism was studied in blood and liver tissue. The aim was to established whether its administration would result in steatosis of the liver. Rats were given sodium salt of beta-escin in water solution orally by gavage in the dose of 10 mg/kg or 70 mg/kg. Analysis of blood samples and liver tissue showed that administration of beta-escin to healthy rats did not induce any substantial changes in the metabolic parameters studied. The rats did not develop steatosis. The biological half-life of antipyrine was only sightly prolonged. (Tab. 3, Fig. 1, Ref. 10.) PMID- 8353758 TI - [What are the costs of septic complications in surgery?]. AB - Infectious complications have remained the most frequent cause of morbidity in surgical patients, and that despite the constantly broadening range of up-to-date antimicrobial drugs administered prophylactically and therapeutically, the improved methods of cultivating microorganisms and of establishing sensitivity to antibiotics. Infections in surgical patients lead to prolonged hospitalization, prolonged working disability, and to increased cost of treatment. Considerable economic consequences of infections in surgical patients are demonstrated on the basis of the authors' clinical material and possibilities of preventing infections and of their treatment are also discussed. (Fig. 1, Tab. 2, Ref. 21.) PMID- 8353759 TI - [Antibiotic therapy in the intensive care unit]. AB - The results of antibiotic treatment administered to 78 patients within one year are reported. Due to the nosocomial nature of the infections, the serious overall condition of the patients and the associated diseases, the prognosis remained unfavourable despite adequate antibiotic treatment. In the group of patients on dialysis ofloxacin and ciprofloxacin proved effective. Patients with exacerbation of chronic bronchitis responded well to doxycycline. In the treatment of infections of the urinary tract, the known favourable effect of cotrimoxazol was confirmed. Of the group of 78 patients with transitory or permanent cardiostimulation, 18 received antibiotic treatment. In 6 of them with transitory cardiostimulation antibiotics were given as a prophylactic measure, 4 patients developed febrile conditions after implantation of the cardiostimulator and 8 patients received antibiotics due to infections of the respiratory and urinary tract. After implantation of the cardiostimulator 60 patients (77%) did not require antibacterial treatment. (Ref. 5.) PMID- 8353760 TI - [Care of the aged population]. AB - Topical problems in the care of geriatric patients are presented. Qualified estimations suggest that subjects above 60 years of age represent more than one half of the daily clientele of a district physician. The basic characteristics of elderly people are their fragility, readily attained decompensation and diminished adaptability. Their hospitalization is thus demanding and involves risks. Geriatric patients require comprehensive care. Treatment without removing their social fears and psychic anxiety does not yield adequate effect. Active involvement of relatives into the program of care may prove a beneficial contribution. The main aim is to provide comprehensive health and social care primarily at the patient's home. (Ref. 10.) PMID- 8353761 TI - [The relation of speech to the right and left cerebral hemispheres]. AB - Verbal speech functions are localized in right-handed subjects nearly exclusively and in left-handed ones mostly in the left hemisphere. Much information on these functions has been obtained by studying patients affected with spontaneous damages, as well as after hemispherectomy, after severing the corpus callosum, and during electric stimulation of the brain in neurosurgical procedures. In the presylvian region of the hemisphere dominant for speech, a region for the production and identification of speech was found, surrounded by an area for shortterm verbal memory. The predominance of the right ear in recognizing verbal stimuli, established by the dichotic test, applies to the population rather than to the individual. The substance of verbal dominance of the left hemisphere lies in the prevalence of its capacity to distinguish rapid acoustic sequences and to produce them. Observations made on deaf-mute patients with sign language have demonstrated that humans possess a genetically determined ability to develop speech, regardless the modality. Speech functions of the right hemisphere concern mostly nonverbal prosodic components of speech. PMID- 8353762 TI - [Genetic disorders in the pediatric population in Orava]. AB - The study is focused on genetic characterization of the child population of the Orava region, where genetic isolates persisted as long as the middle of this century. Active screening for genetic pathology over a period of 5 years involved examination of 1058 children aged 0-14 years. Genetically determined pathological conditions were diagnosed in 757 children, which represents 1.67% of the child population of this region. Chromosomal aberrations were established in 55 children (0.12%), monogenic diseases in 193 children (0.43%), of these autosomal recessive conditions in 88 children (0.19%), and multifactorially determined conditions in 478 children (1.06%). Focal occurrence of an inherited disease was not recorded. Genetic load of the population studied was found to be comparable to that in panmictic populations. The occurrence of diseases inherited as autosomal recessive traits suggests that the influence of genetic isolates does no longer persist in Orava. PMID- 8353763 TI - [Enzymes in tumors of the breast. Histochemical study of the stroma in breast carcinomas]. AB - The results obtained in histochemical examination of the stroma of mammary gland carcinomas allow to draws the following conclusions. The reaction for alkaline phosphatase proved suitable for detecting proliferation zones in the stroma of mammary gland carcinoma. Proliferation of fibroblasts, myofibroblasts, endothelial cells, and possibly also of other cells is involved. At present, myofibroblasts can not be cytoenzymatically differentiated from fibroblasts. The reactions for acid phosphatase and nonspecific esterase provide a quick and reliable picture on the amount of macrophages. The combined reaction for alkaline phosphatase and dipeptidylpeptidase IV in the same section indicates that individual segments of the newly formed capillary bed in the stroma of the tumor, i.e. the arterial, intermediary and venous segment, are differentially equipped by these enzymes. The activity of several enzymes in carcinomal stroma with typical stripe- and wave-like architecture can most probably be assigned to fibroblasts and myofibroblasts. Between the enzymatic activity in the stroma and the type or differentiation of the carcinoma no relationship was established. PMID- 8353764 TI - [Use of the CA 19-9 tumor marker in the diagnosis of pancreatic carcinoma]. AB - The contribution of the tumor marker CA 19-9 to differential diagnosis between malignant and nonmalignant diseases of the pancreas was assessed in a group of 120 patients. On using border values of CA 19-9 80 U/ml, its sensitivity was found to be 84.4% and its specificity 84.8% for carcinomas of the pancreas. Correlation of CA 19-9 values with results of computer tomography and endogenous retrograde cholangiopancreatography in the patients studied yielded an over 80% accordance. In the light of the obtained results, the authors consider determination of CA 19-9 levels to be a suitable method supplementing the imaging examination methods in suspect carcinoma of the pancreas. PMID- 8353765 TI - [Use of high-frequency modulated continuous positive airway pressure in experimental respiratory distress syndrome and pulmonary edema]. AB - The effect of high frequency (f = 300.min-1) modulated continuous positive airway pressure (CPAP) (0.49 kPa) was compared with that of CPAP without modulation (0.49 kPa) in 24 anesthetized rabbits in experimental respiratory distress syndrome (RDS) and pulmonary edema. RDS was induced by single excessive lavage of the lung on using the impulse and expulse effect of high frequency jet ventilation. Pulmonary edema was elicited by i.v. administration of a mixture of fatty acids. Decreased dynamic compliance of the lung and increased respiration work and rate were recorded both in experimental RDS and pulmonary edema. In RDS paO2 was reduced and paCO2 increased. In pulmonary edema, despite diminished respiration volume, ventilation was enhanced by the higher respiration rate and both paO2 and paCO2 were reduced. Application of CPAP resulted in normalization of blood gases. Modulated CPAP, compared to CPAP without modulation, further decreased paCO2 and increased paO2. The results obtained in experimental models of RDS and pulmonary edema in rabbits show the beneficial effect of high frequency modulated CPAP by pressure oscillation on values of blood gas tension. PMID- 8353766 TI - [Relation between blood glucose and insulin in hemodialysis]. AB - In 25 patients with chronic renal failure, the levels of glycemia and immunoreactive insulin (IRI) were determined in one-hour intervals over the period of eight-hour hemodialysis. The study was performed in hemodialysis with and without 200 mg% glucose in the dialysis solution. The mutual behavior of the two substances was evaluated. In patients on a chronic hemodialysis program the level of IRI was found to depend on elimination, secretion, and endogenous control of IRI. The internal processes may be involved to a more important extent in achieving the definitive levels of IRI (middle-molecular substance) than its elimination by hemodialysis. The actual regulator-glucose (low-molecular substance) need not change its level significantly in this process. PMID- 8353767 TI - [The effect of rotating magnetic fields on the growth of Deal's guinea pig sarcoma transplanted subcutaneously in guinea pigs]. AB - The effect of rotating magnetic field (RMF) was studied on the growth of Deals' guinea pig sarcoma (DGPS) transplanted subcutaneously into the inguen of guinea pigs. The 0.2 ml of transplanted suspension contained 1.5-2.0 x 10(6) of vital DGPS cells. Over a period of 24 days the animals were daily two times exposed to RMF for 3 hours. The animals were sacrificed in chloroform anesthesia, the inguinal tumors, lungs and hearts were removed and weighed. The following findings were recorded: 1. RMF inhibited the growth of DGPS cells in experimental guinea pigs compared to control animals (p < 0.001); 2. In the experimental animals DGPS cells did not metastasize into the lung parenchyma; 3. The pathological characteristics of the tumors in the experimental and control group of guinea pigs tended to be different. (Tab. 3, Ref. 14.) PMID- 8353768 TI - [The clinical picture of imported malaria and its relation to P. falciparum parasitemia]. AB - The paper summarizes the results of clinical examinations of imported malaria in 48 patients, semi-immune foreigners infected with P. falciparum and P. vivax/P. ovale. Of the objective manifestations, hepatosplenomegaly was predominant in P. falciparum infections (34%), whereas in P. vivax infections its occurrence rate was 19%. Body temperature over 38 degrees C with shivering had a higher frequency in P. vivax (81%) compared to P. falciparum (41%) infections. Pathologically altered hematologic values, particularly mild to medium increase in sedimentation rate, were found in all patients with P. vivax/P. ovale, while in patients infected with P. falciparum only in those whose parasitemia exceeded 10,000 trophozoites in 1 microliter blood. Reduced values of hemoglobin, hematocrit, and mean erythrocyte volume are indicative of microcytic anemia of mild degree. Biochemical examinations yielded slightly increased values of the thymol turbidity test and mild reduction of serum proteins at simultaneous increase of albumins (8% of the patients examined). Of the parameters of humoral immunity, there was a rise in immunoglobulin values concerning particularly IgG and IgM, and that in all types of malarial infection studied. Increased values of circulating immunocomplexes had a high frequency rate with all plasmodial species, in P. falciparum infections independently of the degree of parasitemia. (Tab. 7, Ref. 13.) PMID- 8353769 TI - [von Hippel-Lindau disease]. AB - The available diagnostic and therapeutic possibilities allow to treat successfully all manifestations of von Hippel-Lindau disease. Adenocarcinomas of the kidneys, however, still present a serious therapeutic problem due to their mostly bilateral and multifocal occurrence. Evidence that patients after bilateral nephrectomy with subsequent dialysis or transplantation would have a longer survival time than patients whose kidneys had not been removed has not been provided as yet. Partial resection or enucleation of tumors may postpone the development of metastases but does not prevent tumor formation in the remaining parts of the kidneys. Considering the late appearance of metastases, though evidence only in one of our patients, we preferred not to remove the kidney and to introduce dialysis. The availability of sonography has put the kidney into the focus od attention in this disease. Not only does sonography allow to monitor regularly members of the affected families but also to screen for the disease at routine sonographic examination of the abdomen. (Fig. 7, Ref. 15.) PMID- 8353770 TI - [The 100th anniversary of Szondi]. PMID- 8353771 TI - [Congenital malformations: care or predict?]. AB - Spectacular scientific and technological advances made in the last decade have had such a profound impact on biological and medical science that they have dramatically modified the citizen's behaviour concerning life events, especially congenital malformation. Prenatal diagnosis (PND) leads to do the diagnosis of almost all fetal internal and external malformations. The matter is, not only to care, but, first to know. The positive efficiency of PND is sometimes preparing the best cares and, of course, to recognize many severe anomalies postnatally diagnosed before PND time, and carrying wellknown 50% rate mortality by neo-natal surgery. Congenital diaphragmatic hernia is pointed out as a good example of it, and of hopes and disappointing in utero foetal surgery. New protocol of assessment of fetal renal function is an appreciated method to do prognosis of some fetal uropathies before late in utero drainage, for a short time waiting for necessary maturation of lungs allowing premature delivery. The possibility to do PND of small and benign malformation leads to ask for the question of utility of to know. In spite of the respect of quality of life, can we really allow this type of human selection to be made? The next knowledges of the human genoma map bring us into the predictive medicine. Using "compulsory" PND is a real risk to practice dangerously, a soft eugenism. PND must be, and remain an outstanding advance to provide better treatment. PMID- 8353772 TI - [Synergism and antagonism between estrogens and progestins: an update]. AB - Our purpose is to provide a review of studies performed since forty five years, concerning interactions of natural or synthetic estrogens and progestins. In this paper, the terms synergism and antagonism have to be considered in a broader sense than usually done. In addition to the classical concepts of succession and of simultaneity synergism between estradiol and progesterone, notions of "saving" and of "necessity" synergism came from decidualization studies in the rabbit (1949). The necessity synergism put definitively and end to the idea that estradiol was only a female hormone and progesterone a mother one. Our research in the field of ovum implantation showed also that estrogens might be secreted by mammalian ova (1949), which is now well established. The participation of estrogens to the process of decidualization in the rat suggested even (1958, 1959) their role in the starting implantation. From 1960, synthetic estrogens and progestins were tested, in a first step especially ethynylestradiol and chlormadinone acetate. In the rabbit and in the rat, these new tools permitted us to dissociate the hormonal needs of embryonic growth and of morphogenesis (1965). The studies related to the effects of these analogs upon the adrenal gland, as upon the hypophysis (1963), led to their clinical use in the treatment of advanced breast cancers, and the studies concerning their effects in the ovulation to the discovery of the antiovulatory synergism of synthetic estrogens and progestins (1966, 1982). These observations are in agreement with the Courrier rules with regard to the relationships between the relative, but also absolute, quantities of estradiol and of progesterone administered, and the obtained biological effects. Nevertheless, progestins exist with incomplete or, on the contrary, superfluous pharmacological activities. In the extreme, the estrogenic properties of norethisterone take precedence over its progestogenic properties when administered doses are growing (1977). These phenomena have now to be understood at a molecular level. Though explanations are presently available for some processes, many of them remain to day unexplained, and inversely other explanations are coming into sight. PMID- 8353773 TI - [Molecular genetics of hemochromatosis]. AB - Haemochromatosis is an inherited disorder of iron metabolism characterized by a general iron over loading. Without diagnosis and early treatment, it is a serious and potentially fatal disease by cardiac failure or hepatocellular carcinoma in particular. Gene prevalence was estimated at 0.06 in Brittany, so that haemochromatosis may be the most common genetic disease in this area. The biochemical defect of the disease is unknown; only one fact is well established: the iron absorption through duodenal mucosa is excessive. However we don't know if it is a primary event. The gene is also unknown but in 1975 it was located on the short arm of chromosome 6, closely linked to the HLA class I region, less than 1 cM from HLA-A. None of the genes coding for the known iron proteins could be the haemochromatosis gene because of their chromosomal localization. In order to locate this gene with precision, we have used a reverse genetic approach now called positional cloning. Characterization of new polymorphic markers and linkage disequilibrium analysis, have led us to locate the gene within a 350 kb region around HLA-A. We have then searched for all the structural genes in this region. Seven new genes have been so identified and located with precision. A structural analysis of these genes was undertaken to find an eventual abnormality in patients. PMID- 8353774 TI - [Occupational arm ailments in musicians]. AB - We began our specific interest in this subject in 1975 and to date have seen and treated over 600 musicians with functional problems of the upper limb. These are common problems affecting over one third of instrumental musicians. Every instrument may have its own specific repercussions. However certain factors may influence their onset: intensive practice; a technique requiring non physiological positioning; a change in technique, instrument or habits; pre existing trauma; psychological predisposition; inappropriate physique. The presentations are varied and the limits imprecise. Muscles, tendons, joints and nerves may be involved. The commonest, and easiest to cure are due to pain resulting from overuse syndromes cover a multitude of sins resulting from marked physical effort in excess of the normal physiological capacity of the body. Joint instability and degenerative disease pose their own specific problems. Peripheral nerve lesions can be related to overuse syndromes or to the adoption of non physiological or harmful positions. The most difficult problems to deal with are those related to a loss of motor control when performing the same repetitive movement--functional dystonia. Their origin remains obscure with the major discussion revolving around either a neurological or organic aetiology. Our intensive experience of instrumentalists with these problems secondary to bad positioning or posture, has led us to propose a therapeutic regime based on structured re-education and relaxation. The great majority of sufferers overuse syndromes or functional dystonias have been able to resume their professional activities. It is clear that functional dystonias are curable if treatment is instituted early and that the lesions are not too long standing. PMID- 8353775 TI - [Celioscopic cholecystectomy]. AB - Laparoscopic digestive surgery is right now like a revolution. The author after a short historic homage to Raoul Palmer who in 1940 realized the first laparoscopy and also to Philippe Mouret and Francois Dubois who performed the first laparoscopic cholecystectomy in the world in 1987, is doing some comments. The comments are based in the experience of the author who performed in his surgical department about 400 cholecystectomies and another study realized with B. Delaitre on 6512 cases showing a decrease of morbidity however a dramatic increase of biliary complications from 1.0/00 to 1% this leads the author to two type of reflexions. One based on technical problem especially in high frequency surgery the other in training of this new surgical technic and also on rapid extension, sometime anarchistic of the indications of this new digestive laparoscopic surgery. In conclusion, we have to performed clinical research before doing next applications of laparoscopic surgery and keep in mind the necessity for a new technic to be better for patients. PMID- 8353776 TI - [Prevalence of gastrocnemius vein insufficiency using color-coded Doppler ultrasound (modifications of the therapeutic strategy)]. AB - The importance of morphologic and dynamic lesions of the gastrocnemius vein is underestimated. Color-coded Duplex scanning was performed in 483 patients with varicosities and 869 legs with some venous abnormalities were discovered. Two types of lesion on gastrocnemius veins were founded: incompetence and dilatation usually located on the medial gastrocnemius vein. In 29.34% of the limbs, a medial gastrocnemius vein incompetence was present and a dilatation in 15.42%. Medial gastrocnemius vein incompetence was associated with a mid calf gastrocnemius communicating vein incompetence in 25%. Physiopathological hypothesis could be drawn of our observations. Gastrocnemius veins when incompetent should be ligated flush to the popliteal vein. The high prevalence of gastrocnemius vein should be considered in the management of varicose veins and color-coded Duplex scanning routinely performed before surgery. PMID- 8353777 TI - [The Hellp syndrome: a frequent (?) obstetric emergency]. AB - Preeclampsia is a multisystem disorder of pregnancy whose clinical presentation is related to the importance and the extent of maternal microvasculature damage. 16 patients with preeclampsia, thrombocytopenia (< 100,000/mm3), elevated liver enzymes and hemolysis are described. Weinstein in 1982 assigned the acronym of Hellp syndrome for this clinical presentation of preeclampsia. This syndrome was seldom recognized during the first years of the study but was diagnosed later on, in 1 pregnancy out of 600 parturitions and in 5% of preeclampsia in 1991. Two out of the patients developed eclamptic seizures. The mode of delivery was as follows: 9 out of 16 had an emergency Caesarean section; the 7 other patients had vaginal delivery after induction of labor. Delivery occurred before 32 weeks of gestation for 6 out of 17 newborns. Outcome was good for 14 of the 17 newborns (one twin pregnancy). Two fetuses died: one in utero and one during interruption of the pregnancy at 24 weeks of gestation. A small for gestational age preterm of 32 weeks died on his second day of life. Early diagnosis of Hellp Syndrome, especially when abdominal pains are present, allows a prompt management of these patients, including delivery, which appeared in our experience, the only way to avoid fetomaternal complications. The thrombotic microangiopathics and acute fatty liver of pregnancy are potential imitations of Hellp syndrome and they must be considered for differential diagnosis. The frequency of Hellp Syndrome varies from one study to another. It can be increased up to 6 fold if referred to the number of pregnancies and up to 3 fold if referred to the number of preeclampsias. These differences can be real but may be due to bias related to differences in practice between centers and also differences in definitions of Hellp Syndrome and preeclampsia. PMID- 8353778 TI - [A new entity of sperm pathology: peri-axonemal flagellar dyskinesia]. AB - The study of 17 infertile men has led to define a new entity of sperm pathology as part of the more general field of flagellar dyskinesias. Sperm parameters of the studied patients and a control series have been first estimated by routine analysis (concentration, motility, morphology). To precise their characteristics, kinetic and ultrastructural investigations, as the zona-free hamster oocyte penetration test, have been performed. Sperm parameters of the studied cases, as revealed by routine analysis, were close to the control group. However, a major kinetic anomaly was found which was characterized by an important decrease of the amplitude of lateral head displacement (1.6 microns vs 5.3 microns, p < 0.001), although the progressive velocity was only slightly impaired (20.3 microns vs 24.9 microns, p < 0.05). Electron microscopy revealed anomalies limited to the peri-axonemal structures such as the outer dense fibers and the fibrous sheath. Rates of sperm-oocyte attachment were normal but rates of oocyte penetration were low (27.7% of decondensed sperm heads vs 85.6%, p < 0.001). Attempts to assisted fertilization with the studied patients (51 cycles of insemination, 8 cycles of in vitro fertilization) were unsuccessful. All these data suggest that the infertility can be attributed to the movement disturbances which should impair sperm propulsion throughout the cervical mucus and the zona pellucida. PMID- 8353779 TI - The critical care unit. In search of management. AB - Given the impending crisis in health care economics, all segments of the health care industry must maintain quality while becoming more efficient and cost effective, particularly the critical care units that are disproportionately large consumers of the health care dollar. This article reviews the managerial and administrative issues, responsibilities, challenges, and demands that confront unit directors now and in the future. Also, this article provides a context and framework for all following articles in this volume. PMID- 8353780 TI - Intensive care units in the triage mode. An organizational perspective. AB - Decisions to admit and discharge patients to and from the intensive care unit (ICU) when resources are scarce should be made according to the triage principle- that is, resources should be allocated based on the patient's ability to benefit from critical care. The ICU organizational structure and the constraints on decision-making processes are discussed in this article along with strategies for improvement in both areas. PMID- 8353781 TI - Management as the art of politics. AB - This discussion has furnished a personal view of some of the features involved in managing a busy surgical ICU. Experience has provided the reference frame rather than an extensive literature search and associated bibliography. Physician involvement in ICU management depends on the character of the institution and the ability of the director to influence physician, nursing, and ancillary staff behavior by force of personality rather than by relying on universally accepted behavioral covenants. The issues raised are controversial and should provoke more discussion than acceptance. It is to be hoped, however, that some of the points will be recognized as common problems requiring solution in all similar environments. "Management as the art of politics" summarizes the 1980s' approach to ICU governance, and it is fitting to question its acceptability in an era of cost containment, resource restriction, and increased awareness of the rights of a patient and his or her family to control the extent of medical care rendered. Laissez faire management is unacceptable today, and future governance will reflect increased responsibility for unit managers and the realization that the ICU is an institutional and societal resource that cannot respond to the prerogative of individual users. The Magna Carta of ICU governance remains to be written. It is inappropriate for ICU managers to assume responsibilities that preclude the prerogative of the admitting physician and appropriate medical consultants. It is equally important, however, that the medical community recognizes the importance of adjudicating access to and care within ICUs. Scarce medical resources used in these areas represent as much as 20% of all medical expenditures, the bulk of which is spent in unsuccessful ventures. Management of this resource cannot be relegated to inexperienced, naive, or self-serving clinicians. The tools for managing the ICU in the '90s have been introduced, and they will begin to define the new concept of a successful outcome following admission. Clinicians traditionally have focused on individual patients, and this approach has led to many improvements in care. The next challenge facing the ICU management team will be to organize the process of patient care that will ensure the best possible individual outcome while promoting general efficiency of the available resources to function for all. Physician and nurse managers will be co responsible for adjudicating a complex, costly, and vital hospital resource; the price of failure is unacceptable.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8353782 TI - Establishing an administrative core curriculum for critical care physicians. AB - Summary recommendations for a core curriculum in intensive care unit administration and management are presented for inclusion in critical care medicine fellowship training programs. Attention is focused on program content and teaching formats that may be adapted to various educational priorities. PMID- 8353783 TI - Critical care management in the 1990s. Making collaborative practice work. AB - The creation of a partnership, the hallmark of true collaborative practice, is an ongoing, dynamic process. It demands commitment, energy, and creativity. It is learned and therefore must be role modeled. One must remember that it takes time to develop collaborative relationships. One must begin slowly, walk not run, and have realistic expectations. It is a joy to work in an environment that has developed and is in the process of continually developing true collaborative practice. Hope for the future of health care lies in our ability to deliver coordinated and collaborative care. Nursing, medicine, and administration together can and must provide the solutions to our health care delivery problems before those solutions are legislated. We must set policies and priorities to appropriately allocate scarce resources. We must address personnel needs, credentialing, and compensation to ensure adequate numbers of qualified staff to meet the growing needs of our patients. We must evaluate technology and our physical environments to determine the types of services that we will offer. We must continue to broaden our collaborative efforts to extend from the patient care arena into the realms of education, research, and administration. It is up to each of us and each of our colleagues to work every day toward a more collaborative practice environment. By empowering each other, we can put into place a collaboration which "works jointly with others in intellectual endeavors" rather than one which merely "cooperates with an enemy force." PMID- 8353784 TI - Total quality management in the critical care environment. A primer. AB - Quality management has become issue No. 1 in organizations throughout the country. Hospitals have joined this crusade and are embarking on their own programs to maintain their competitive edge. TQM or CQI has been identified as showing great success in achieving quality. As TQM systems begin developing in hospitals, CCUs will be called on to join in these efforts. By understanding what TQM is, how it is used, and how it can be applied, CCU staffs will be able to incorporate TQM in their own practices. By choosing projects carefully, using scientific measurement in clinical and nonclinical areas, and developing a team based approach, the CCU staff can achieve improved clinical outcomes as well as improved procedures that result in better staff and patient satisfaction. PMID- 8353785 TI - Current and emerging legal issues in critical care. AB - Antitrust, access to care, and accountability are but three areas of law directly affecting the provision of critical care services. As the country continues to wrestle with increased health care costs, the expanding needs posed by an aging population and problems such as the AIDS epidemic, and whether or not to adopt some form of national health insurance, the legal system will continue to interact with the health care delivery system. Providers of critical care services are in the forefront of advances in medicine and are in the middle of the political, economic, and policy debates about the shaping of the health care system. They must not allow themselves to be caught at the end of rapid changes in the legal system. Critical care providers must take a leadership role in helping shape the forces that will be the major legal issues in years to come. If providers do not like lawyers and bureaucrats telling them how to provide patient care, they must seize the initiative in shaping defined standards of care. If providers do not like to be forced into providing "useless" or "unnecessary" care, they must be more honest in discussing care options with patients, families, and the media. If they do not like being told for how long to hospitalize a patient, they must be more responsible in making decisions to admit, transfer, or discharge a patient. Lawyers have been quite happy to step into what has long been perceived as a vacuum of leadership among medical care providers, and will continue to do so as long as there is uncertainty and lack of consensus about what constitutes appropriate medical care. PMID- 8353786 TI - ABCs of quality assurance. AB - The following six points offer a summary of principles to the manager who must develop a QA program: Institutional commitment to the QA process is essential for success. This must be embodied in the table of organization for QA and the commitment of resources to the task. The QA plan should address mechanisms for data collection, data review, and outcome reporting. Lines of responsibility should be stated clearly. The manner in which the outcomes of the QA process are implemented and communicated back to the front-line workers must be clearly stated and continually fed back to them. Clinical evaluations work best in the presence of politically neutral practice guidelines. Vociferous complainers frequently can be made part of the process, harnessing their energy to good effect. Self survey should precede an accreditation site visit by at least 6 months. The best sources of JCAHO thinking on QA methods are the many JCAHO publications, several of which focus on the critical care arena. PMID- 8353787 TI - Technology and equipment: essentials of the art of evaluation, negotiation, and acquisition. AB - The competition for scarce finances for equipment/technology purchases can be won with careful preparation and documentation. Planning and implementing effective negotiation strategies can lower the cost of new technology acquisitions. PMID- 8353788 TI - Clinical engineering support for the critical care unit. AB - A tremendous selection of choices, both for goods and services, is available in the health care industry. Unfortunately, even marginal increases in expenses are hard to rationalize in today's market. To squeeze every bit from every dollar requires very active and dynamic leadership. Regulatory requirements, with the requisite documentation, must be met efficiently to free the organization to concentrate resources on providing primary health care. Capital dollars can be spent only on the best value to meet corporate objectives. The processes of health care delivery, risk assessment and management, and technology acquisition must be integrated on a corporation-wide scope to optimize the final product. To this end, the clinical engineering department brings essential skills to this participatory, dynamic management of modern health care facilities. This process of technology management has been implemented in various hospitals since 1985. Taking lessons from industry, hospital administrators are focusing management resources to address specific concerns. Clinical engineering, with its technical expertise, practical knowledge in the delivery of health care, and accrued database, is an essential part of this process. This technology management process involves an integration of experts to find specific solutions, and the supporting policies and procedures to ensure universal use of technology management. PMID- 8353789 TI - Organization and management of critical care systems in unconventional situations. AB - Critical care medicine is a field of medicine using the highest concentration of expensive diagnostic and life-support technology for the benefit of a single individual. Conventional use of this resource and specialty is clearly understood, despite the fact that it is not necessarily comparable among different institutions. Some of the major issues in using critical care as a medical tool during extraordinary stress on the hospital, and the potential for using it in unconventional environments outside an established institution, have been reviewed. It is clear that the expertise and multidisciplinary approach can be of great use in disaster response, and a national effort toward integrating critical care into overall medical response is in progress. PMID- 8353790 TI - Using severity measures to describe high performance intensive care units. AB - This article describes the use of various scores and probabilities to clinically categorize patients in the adult intensive care unit. Some of the limitations of these severity measures are reviewed including variable definitions, timing of measurements, and whether models can be used for individual patients. Also, this article discusses how probability models may be used to compare similar types of intensive care units using standardized clinical and cost performance indices. PMID- 8353791 TI - Admission, discharge, and triage in critical care. Principles and practice. AB - This article reviews the practices of admission, discharge, and triage to or from a special care unit and how they differ based on unit type and patient load. The need to solve the excess patient/insufficient resources dilemma is also addressed. PMID- 8353792 TI - The ethics of medical futility. AB - This article traces the evolution of the debate between the futility of cardiopulmonary resuscitation and the patient's right to consent, analyzing its origins in the 1970s and examining new policies recommended by the American Medical Association in 1991. PMID- 8353793 TI - Rationing health care. Impact on critical care. AB - Critical care practitioners are faced with ethical dilemmas every day. The increasing costs of health care coupled with the scarcity of resources, including critical care nurses, have created yet another ethical dilemma--rationing of health care. Rationing of critical care is occurring today and current conditions indicate that these decisions will become an increasing issue in the delivery of critical care services. This article identifies some of the ethical issues associated with the rationing of critical care and examines the foundations of ethical thought upon which such decisions can be based. Understanding the overall cost containment movement as well as the potential problems associated with medical gatekeeping will allow critical care practitioners to better deal with the ethical dilemmas of today as well as help them anticipate those that will arise in the near future. PMID- 8353794 TI - Regionalization and categorization of critical care services. AB - Regionalized systems of care match the medical needs of individual patients to available resources. Hospitals are categorized based on their personnel and technologic resources. Triage guidelines, based on severity of disease, are developed to link patient types to hospital categorization levels. Regionalization requires major planning, publicity, and educational efforts to implement an ongoing coordination and continuous quality improvement to function. PMID- 8353795 TI - Death in America: a clinician's perspective. AB - In America today, the practices of medicine and law have so interfered with the dying process that death has become a perversion of the natural process. In order to better understand death in American society, this article addresses the moral ethical issues, individual rights, state regulatory laws, and other medico-legal concerns. PMID- 8353796 TI - Immunosuppressive therapy following cardiac transplantation. PMID- 8353797 TI - Combining vasoactive infusions for maximal cardiac performance in the postoperative period. PMID- 8353798 TI - Angiotensin converting enzyme inhibition: pharmacologic management to minimize postinfarction heart failure. PMID- 8353799 TI - Hypertensive crisis in the 1990s. PMID- 8353800 TI - Comparisons and controversies in clot buster drugs. PMID- 8353801 TI - Role-modeled visiting compared with restricted visiting on surgical cardiac patients and family members. PMID- 8353802 TI - Annoyance to ICU noise: a model of patient discomfort. PMID- 8353803 TI - Remission of Philadelphia positive chronic myelogenous leukemia associated with t(3;21) after bone marrow transplantation. AB - We here report a male patient with an additional t(3;21)(q26;q22) in Philadelphia positive chronic myelogenous leukemia (Ph + CML). In spite of the presence of this progression of disease marker and probably related to alpha-interferon therapy, this case entered into remission as a second chronic phase. At that time, he underwent allogeneic bone marrow transplantation. One year after BMT he showed a disappearance of leukemic clones at the cytogenetic and molecular levels. At present the patient has 21 months of clinical and hematologic remission. It is of interest to note that the association of alpha-interferon hydroxyurea and bone marrow transplantation might produce a negative selection pressure against the leukemic clone in this patient. PMID- 8353804 TI - Blastic phase chronic myeloid leukemia with a four-break rearrangement: t(11;9)(9;22)(q23;p22q34;q11). AB - Chromosome analysis of bone marrow (BM) aspirate from a 36-year-old man with chronic myeloid leukemia (CML) in blastic phase (BP) showed a four-break rearrangement t(11;9)(9;22)(q23; p22q34;q11), which can be considered a t(9;22)(q34;q11) and a secondary t(9;11)(p22;q23). It is not surprising that additional chromosome abnormalities occur in patients with Ph-positive CML in BP, but it is of interest that t(9;11)(p22;q23), characteristic of acute myeloid leukemia French-American-British (FAB) type M5 (ANLL-M5) was observed. The possible meaning of this additional change in BP of CML is discussed. PMID- 8353805 TI - Myeloid leukemias and myelodysplastic syndromes: chemical exposure, histologic subtype and cytogenetics in a case-control study. AB - We conducted a case control study of 50 acute myeloid leukemias (AML), 17 chronic myeloid leukemias (CML), 19 myelodysplastic syndromes (MDS), and 246 controls. The cases were classified according to the French-American-British (FAB) classification, and chromosome aberrations were recorded according to the International System for Human Cytogenetic Nomenclature. Exposure to suspected leukemogenic agents was assessed blindly by an industrial hygienist. Increased risks were noted for mechanics, welders, electricians, and drivers among men and among farmers and textile workers among women. Increased SMRs for leukemias in a census-based cohort study conducted in the same area (Torino) were previously reported for electricians and drivers among men and for textile workers among women. We detected nonstatistically significant increased relative risks for exposure to benzene (odds ratio, OR = 1.7), petrol refining products (1.9), polycyclic aromatic hydrocarbons (1.7), and electromagnetic fields (1.6) in men; in women, a statistically significant association with exposure to pesticides was detected [OR = 4.4; 95% confidence interval (CI) 1.7-11.5]. Although exposure to pesticides was confined to AML, MDS cases included a high proportion of subjects exposed to benzene and electromagnetic fields. No particular histologic subtype of AML was associated with chemical exposures except for that of pesticides with the M4 category. Chromosome aberrations were not associated with chemical exposures (OR = 1.0), but a nonstatistically significant excess was noted in association with electromagnetic fields (OR = 2.1). PMID- 8353806 TI - Two additional cases of acute myeloid leukemia with t(7;11)(p15;p15) having low neutrophil alkaline phosphatase scores. AB - We report two additional patients with acute myeloid leukemia (AML) and a translocation between chromosomes 7 and 11: t(7;11)(p15;p15). One patient was diagnosed as having AML-M2 and the other as AML with myelofibrosis. Both patients had low-level neutrophil alkaline phosphatase (NAP) scores. In the literature, only 15 AML patients with t(7;11)(p15;p15) have been reported; nine of them had an AML-M2 morphology, and all had a decreased NAP score. Moreover, mean survival of the reported AML patients with t(7;11)(p15;p15) was 15 months, although 85% of them obtained complete remission, indicating that this type of leukemia frequently tends to relapse. These findings indicate a strong association between the chromosome abnormality and hematologic manifestations of this disease. PMID- 8353807 TI - Trisomy 4 and de novo acute myelomonocytic leukemia in a Kuwaiti patient. AB - Trisomy 4 is a rare but specific karyotypic abnormality associated with primary and secondary acute myeloblastic leukemia (AML). We report such an occurrence in a Kuwaiti patient with de novo acute myelomonocytic leukemia and its disappearance on achievement of complete remission. PMID- 8353808 TI - Cytogenetic abnormalities detected by direct analysis in a case of choriocarcinoma. AB - Malignant trophoblastic cells from a case of choriocarcinoma were cytogenetically investigated by direct analysis of fresh tissue from the tumor. To our knowledge, previous cytogenetic studies have been performed only on established cell lines. In this study, 54 metaphases were observed, of which 41 were fully karyotyped. Three chromosomally abnormal lines were identified. In all of them, trisomy 3 and 10, a supernumerary isochromosome 1q,i(1)(q10), an i(8)(q10) replacing one chromosome 8, and a marker chromosome were observed. In addition, involvement of chromosome 12 was observed in two of the three lines, trisomic in one and an i(12)(q10) in the other. PMID- 8353809 TI - Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors. AB - Cytogenetic analysis of 184 adipose tissue tumors, 175 lipomas, and nine liposarcomas (LPS) showed the presence of a ring chromosome and/or a long marker chromosome in 10 cases with common histologic features such as atypical stromal cells with or without lipoblasts. In five of the cases, this appeared to be the sole cytogenetic abnormality. Fluorescence in situ hybridization (FISH) analysis with a microclone library specific for chromosome region 12q13-q15 showed extensive staining of the ring and long marker chromosomes, indicating that genetic sequences of this particular region of chromosome 12 are present in these marker chromosomes, most likely in an amplified form. PMID- 8353810 TI - Rationalization of in situ hybridization: testing up to 16 different probes on a single slide. AB - Although particularly interested in tumor research, investigators in many tumor cytogenetics laboratories cannot afford extensive molecular/interphase cytogenetics studies in addition to routine cytogenetics analyses, primarily because many slides must be stained to examine a few cases using a panel of centromeric probes. Moreover, fluorescence in situ hybridization (FISH) techniques mostly require freshly prepared reagents, such as hybridization mixtures or antibody solutions. These technical requirements are very time consuming, thus limiting their use in routine screening. We report a significantly economical method for rapid performance of interphase cytogenetics in great numbers of cases. The major advantage if its superior efficiency: up to 16 different probes may be used on one single slide. Moreover, the method is significantly cheaper than other techniques owing to minimal probe consumption. The technique is also best suited if great numbers of new probes, e.g., polymerase chain reaction (PCR)-generated YAC-probes, must be tested for their applicability in FISH. PMID- 8353811 TI - Eosinophilia in myelodysplastic syndrome with a (12;21)(q23;q22) translocation. AB - Cytogenetic analysis of bone marrow (BM) cells from a patient with myelodysplastic syndrome (MDS) associated with eosinophilia showed a 45,XY,t(12;21)(q23;q22), -17 karyotype. We performed clonal and suspension cultures using the patient's BM mononuclear cells to clarify the mechanism of eosinophilia. Eosinophil colonies formed in the presence of interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not in the presence of IL-3. When BM cells were cultured in suspension in the presence of IL 5, they differentiated to mature eosinophils, and chromosome analysis identified the 45,XY,t(12;21)(q23;q22), -17 karyotype in all metaphases. The patient's serum did not stimulate eosinophil proliferation or differentiation in comparison with normal serum, however, these data suggest that the abnormal clone with 45,XY,t(12;21)(q23;q22), -17 karyotype may have an increased responsiveness to IL 5 and GM-CSF, resulting in eosinophilia. PMID- 8353812 TI - Toxicity of bile acids to colon cancer cell lines. AB - Quantitative aspects of bile acid cytotoxicity to colon cancer cell lines were investigated because of the etiological role in colon carcinogenesis attributed to the toxic effects of bile acids on colon mucosal cells. The cytotoxicity of major colonic bile acids differed. Lithocholate was the most toxic, followed by chenodeoxycholate and deoxycholate, with cholate being non-toxic over the concentration range studied. Cytotoxicity increased with time of exposure. Values for IC50 for some of the acids were determined to be in the physiological range, as estimated from their concentrations in fecal water. The results suggest dietary factors that contribute to bile acid mucosal damage. They also identify factors of possible importance in the association of high concentrations of bile acids in fecal water with risk for colon cancer. PMID- 8353813 TI - The correlation of response with plasma pharmacokinetics and polyamine concentrations in patients with acute myelogenous leukemia receiving amonafide. AB - We have investigated the correlation of clinical responses (decreases of white blood cells and peripheral blasts) with pharmacokinetic and pharmacodynamic parameters in patients with acute myelogenous leukemia who are receiving amonafide. The increase of plasma polyamine concentrations was used as a measure of tumor sensitivity (pharmacodynamic effect). The correlations between pharmacokinetic parameters (biological half life, area under the concentration time curve (AUC), total plasma clearance), decreases of total white blood cells and peripheral leukemic blasts were weak (maximum r = 0.47). Correlations of response with polyamines were better than those with pharmacokinetic parameters, but not exceptional; of these, the best correlations were with the increase of putrescine. On the other hand, correlations of combinations of AUC and increases of plasma polyamine concentrations with decreases of total white blood cell counts approached unity. Unexpectedly, decreases of peripheral leukemic blasts were correlated just as well with putrescine increase alone (r = 0.91, P = 0.003) or with a combination of polyamine increases and AUC (r = 0.92, P = 0.036). PMID- 8353814 TI - Impairment of fibrinolysis during the growth of two murine mammary adenocarcinomas. AB - The fibrinolytic activity present in the euglobulin (EU) fraction of BALB/c mice before and during the growth of M3 and MM3 murine mammary adenocarcinomas was characterized. The main plasminogen activator (PA) form contained in EUs from control mice was defined as murine urokinase-type PA (uPA). Overall fibrinolytic activity decreased significantly during tumor development. Zymographies showed that this fall was associated with a reduction in the free uPA band (47 kDa) and to the detection of a tissue-type PA (tPA) complexed band (117 kDa). Western blotting showed free tPA protein (68 kDa) in control mice, that disappeared in M3 tumor-bearing mice. In this model, high subcutaneous tumor burden induces a severe impairment in the circulating fibrinolytic system. PMID- 8353815 TI - [Preliminary investigation on the epidemiology of migraine in China]. AB - The prevalence of migraine was investigated in all provinces, municipalities and autonomous regions (except Taiwan) of the People's Republic of China. Random sampling from provincial capitals and from rural areas according to demonstration were used. Among a total screened population of 3,837,597 persons, there were 37,808 cases of migraine. The morbidity and the annual incidence rate were 985.2/100,000 and 79.7/100,000, respectively. The male/female ratio was 1:4. Inland plateaus were higher morbidity areas (more than 1,500/100,000) and coastal provinces and cities were lower morbidity areas (less than 400/100,000). The incidence rate was higher in spring in the south, while it was higher in summer in the north. The incidence rate was higher in hot and damp climate. The morbidity under 14 years old in China was significantly lower than those in overseas reports. PMID- 8353816 TI - [A comparative analysis of current conditions of oral health between residents living in towns and those in countryside in Guangdong Province]. AB - A sampling population of 23,665 in Guangdong Province including 4 towns and 4 countryside had been surveyed for the current situation of oral health. A comparative analysis of residents between towns and countryside had been conducted and the results indicated that the rural residents had a higher prevalence rate of dental caries (65.30%) than those who lived in towns (59.96%). The Decayed Missing Filling (DMF) of the population (4.62) and of the patients (7.08) in countryside were both significantly higher than those (2.86 and 4.78, respectively) of citizens (P < 0.001). Females had a higher rate of dental caries than males both in towns and in countryside. Citizens had a higher prevalence rate of periodontosis than rural residents. This paper also presents a comparison of jaw deformity and personal health behaviour, an age distribution of dental caries and a multiple regression analysis. PMID- 8353817 TI - [A preliminary report on the preparation of antisera against Haemophilus influenzae]. AB - The antigenicity of 5 strains of serotype b Haemophilus influenzae was compared. Strain 58534 showed a higher titer than the rest four. Three lots of antisera were made by immunizing rabbits with 6 strains of Haemophilus influenzae. The results indicated that the antibody titer against strain 58534 also showed a higher level, and the titer only dropped by one dilution after stored in cool place for half a year. We considered that Haemophilus influenzae serotype b strain 58534 is a good strain for the preparation of antiserum against Haemophilus influenzae. PMID- 8353818 TI - [A study on transmission of dengue virus by Culex fatigans]. AB - Patients with acute dengue fever within 2 days of onset were simultaneously bitten by Culex fatigans, Aedes aegypti and Aedes albopictus, which were fed and incubated in the laboratory. Isolation and quantitative assay of dengue virus and transmission experiment were conducted on specimens collected from 3 kinds of mosquitoes at different time. The result showed a positive rate of 5.13% (2/39) and an average viral titer of 2.41 logTCID50, for Culex fatigans, which indicates that Culex fatigans might be naturally infected with dengue virus and might transmit dengue virus after infection. But the positive rate and infection rate of Culex fatigans were significantly lower than those of Aedes aegypti and Aedes albopitus, which indicates that Culex fatigans might play a less important role in the transmission of dengue virus. PMID- 8353819 TI - [An epidemiological investigation on lung cancer and other tumours among coal workers with pneumoconiosis]. AB - A retrospective cohort study was made on lung cancer and all tumours among coal workers with pneumoconiosis in the Haibowan Mining Bureau. Results indicated that the mortality of lung cancer among workers with pneumoconiosis was distinctly higher than that among the local population (P < 0.005, RR = 56.1, AR = 225.2, SMR = 8.07, P < 0.01). The mortality of all tumours among staffs and workers in the Haibowan Mining Bureau was 599.4 per one hundred thousand, but only 62.5 among the local population (P < 0.005). It is suggested that lung cancer in workers exposed to coal dust for more than 18 years should be regarded as occupational cancer. PMID- 8353820 TI - [A study on the relationship between Helicobacter pylori and chronic gastritis and peptic ulcer by the case-control method and sequential analysis]. AB - The association between Helicobacter pylori and the chronic gastritis and peptic ulcer was investigated by the case-control method, 1:1 matched study and sequential analysis. The results of three methods showed that the degree of association between Helicobacter pylori and the chronic gastritis and peptic ulcer was significant (chi 2 = 22.70, P < 0.001, OR = 15.63, 95% CI of OR was 5.05, 48.43), especially that between Helicobacter pylori and active chronic gastritis (OR = 20.92). The results indicate that Helicobacter pylori might be an etiological factor for patients with chronic gastritis and peptic ulcer. PMID- 8353821 TI - [A report on investigation of an outbreak of Legionnaires' disease in a hotel in Beijing]. AB - During the period from February to March, 1992, an outbreak of upper respiratory infection (influenza-like syndrome) took place in a hotel in Beijing. An epidemiological investigation and bacteriological examination were carried out in this hotel. The results showed that it was an outbreak of Legionnaires' disease caused by Legionella pneumophila serogroup 10 (Lp10): The incidence was 13.51% (5/37). This is the first report on LP10 infection in China. PMID- 8353822 TI - [Ureaplasma urealyticum and intrauterine infection of fetus]. AB - Ureaplasma urealyticum (Uu) infection in pregnancy can lead to a poor outcome. To confirm the relation between Uu and intrauterine infection, 65 placentas were taken for isolation and identification of Uu from pregnant women with positive antibody to Uu. Uu was isolated from 13 (20%) of the 65 placentas. The pathologic examination of 6 placentas showed that there were acute or chronic inflammatory cell infiltration. Cord blood IgM antibody was examined by ELISA from 5 cases in which Uu was isolated from placentas and 3 of them was positive to Uu. The 5 cord blood specimens were assayed by the metabolic inhibition test for serotypes of Uu, and one of them was serotype 8. Since the isolation of Uu from some pregnant women, the pathologic changes of placentas, and the detection of specific IgM from cord blood showed a good consistency, we conclude that the Uu infection may occur in utero. PMID- 8353823 TI - [A study on a local epidemic of dengue fever in Shaxi district of Zhongshan city, 1991]. AB - An epidemic of dengue fever occurred in Shengshi Village of Shaxi District in the last ten-day period of August, 1991. A wrong diagnosis was made on account of atypical clinical symptoms and careless investigation during early days. Effective measures had not been taken in time, so that the disease spread to neighbouring three villages and the town. The epidemic lasted for 64 days and 112 cases were found. It had been proven by etiologic studies that type 1 dengue virus caused this epidemic. PMID- 8353824 TI - [An investigation on smoking situation among middle school students in Japan and in Jiangxi, China]. AB - The past smoking rate among middle school students in Jiangxi was 30.5%, which was higher than that in Japan (25.4%). However, the present smoking rate and the frequent smoking rate among middle school students in Jiangxi are 5.8% and 1.1%, respectively, which are far lower than those in Japan (8.7% and 5.3%). The past smoking rate among boy students at each academic year in Jiangxi was higher than that in Japan, but the statistical indices of the present smoking rate and of the frequent smoking rate among boy students and among girl students at each academic year are lower than those in Japan. In Japan, the smoking rate among middle school students in cities was higher than that in the countryside, but vice versa in Jiangxi. The average number of cigarettes consumed per day in Japan was higher than that in Jiangxi. This investigation indicates that the smoking rate among middle school students was much influenced by their friends and relatives, health education in schools, self-feelings about school life and attitude towards smoking, etc. PMID- 8353825 TI - [A matched case-control study on 87 cases of congenital malformations]. AB - In order to investigate the risk factors of congenital malformations, a case control study on congenital malformations with 87 matched pairs was carried out in hospitals of Yinchuan area. The results showed that the risk factors of the congenital malformations in this area were mainly nocuous mental stimulation during early pregnancy, hyperemesis gravidarum, parturient personality (high scores of psychoticism and neuroticism), degree to parturient education and exposure to other detrimental factors in early pregnancy, smoking habit of neonate's father, and so on. PMID- 8353826 TI - [The first report of 2 imported AIDS cases in Guangzhou]. AB - In March and May 1991, two imported AIDS cases were reported for the first time in Guangzhou. We investigated the cases and found that they have been misdiagnosed, because the doctors were not well familiar with this disease. The investigation showed that clinicians must improve their diagnostic ability. And the surveillance on AIDS must be carried out. PMID- 8353827 TI - Dynamics of the effects of levoprotiline and maprotiline on EEG in patients with major depressive episodes (DSM-III-R). AB - The presented study compares the effect of the well-tested antidepressant maprotiline and a new antidepressant with an atypical pharmacological profile, levoprotiline, on EEG during repeated assessment after single dose administration. From the original number of 34 patients fulfilling the criteria of a major depressive episode (DSM-III-R) on account of a low-voltage record or pathological findings 11 were eliminated. To 12 of the remaining patients levoprotiline was administered and to 11 maprotiline, after a one-week placebo period, in doses of 150 mg. The EEG was recorded after an accommodation session immediately before, 1.5, 3, 4.5, 6 and 24 hours after a single dose administration. The record was taken on a 16-channel average reference montage at rest with closed eyes. Two-minute intervals were divided into 30 four-second periods at a sampling frequency of 128 Hz. From the signal by means of FFT the spectra were estimated and the mean spectrum for the entire recording was calculated. This was then divided into 10 frequency bands. The new method of frequency analysis of alpha-entropy was also used which is a global measure of the difference between two spectra. Three hours after administration of a single dose levoprotiline had an EEG profile corresponding to the profile of tricyclic antidepressants, i.e. it increased the values of the power spectra density in the region of 5-8.5 Hz and in the entire beta band; the decline of power in the alpha band was, however, absent. As regards maprotiline, 3 hours after administration a profile typical for antidepressants was not found; obviously because of the great variance of values of power spectra density as a result of great interindividual differences in the ingestion phase. Changes of the EEG spectrum expressed as values of alpha-entropy during different periods of apparently assessment are not incidental. After the initial rise of values a decline occurs. PMID- 8353828 TI - [Detection of cerebropathy in neurologic and psychiatric diseases]. AB - The authors made a comprehensive examination of 16 patients--epileptics, alcoholics, psychotic subjects and patients after cerebral contusion. The patients were subjected to a neurological, psychiatric, psychological examination as well as to a morphological examination (X-ray, CT, NMR), physiological examination (EEG, polysomnography, evoked potentials), immunological examination and SPECT. The majority of patients had positive CT and SPECT findings suggesting focal brain damage. These results could be explained only in exceptional cases by injury, the majority was of unknown aetiology. With this corresponded focal EEG abnormalities and in particular sleep disorders, sometimes subjective but always detectable by objective methods. There was always a shortage of REM, sometimes also NONREM sleep. Half the patients were subjected to an immunological examination which was always positive and comprised elevated acute stage proteins and proteins associated with the stress reaction. Numerous data in the literature and the authors' experience indicate that the mentioned pathological findings are not incidental and form, independently on the aetiology, an integrated unit for which the term cerebropathy can be used. A primary role is played by the epileptic focus and its quality, i.e. above all the rate of discharge and site and humoroergic systems of the brain stem, in particular their efficiency and mutual balance. The events have a programmed sequence. At the beginning an epileptic focus develops which influences the surrounding area, secondary and tertiary foci are formed and the thalamo-cortical system is affected. Soon this is followed by an apparent influence of the epileptic activity on structures of the brain-stem. The consequence are changes affecting sleep, mood, mental performance, immunity, endosecretion and paroxysms. Subsequently individual symptoms are already prepared but have a different latency of manifestation and the latter depends also on external provoking influences. The thalamo-cortical reaction is characterized by the manifestation of epileptic paroxysms and sets in after a different interindividual incubation following injury. The same applies to the hippocampal reaction manifested by the organic psychosyndrome. Some symptoms such as changes of immunity, sleep or endosecretory function are not necessarily manifested if the influence of the focus on structures of the brain stem is not sufficiently intense. Conversely if the effect on the brain-stem and limbic structures is greater and the effect on the thalamo-cortical system smaller, psychotiform behaviour develops. Then there are marked changes of phoria, dynamogeny, rate, affectivity, sleep and hormonal secretion and its equilibrium. PMID- 8353829 TI - [Ethical problems in modern sexology]. AB - The paper is focused on problems of sexual minorities. The authors discuss their position in society, terminological problems and in particular questions associated with ethical problems of treatment of paraphilics. The authors differentiate between essential, possible and not indicated therapeutic provisions. They also focus attention on ethical aspects of different types of treatment of sexual delinquents (surgical, pharmacological and psychotherapeutic methods), whereby they emphasize in particular the necessity to obtain the patient's informed consent. According to the authors skilled therapy gives a chance to reintegrate the paraphilic patient into society and to protect victims delinquent sexual behaviour. PMID- 8353830 TI - [Summary of results of a study of heredity of intelligence in a sample of the Czech population. III. Longitudinal and genealogic study of twins and their families]. AB - The author presents further results of the longitudinal study of inheritance of intelligence, its components and structure in twins. Summarized results are presented for the age period from 0-15 years as well as detailed results of individual components and the global IQ in the age group of 8-15 years. The paper follows after two previous ones published in 1988 where the applied methods and statistical evaluation were described. Evidence was provided that heredity of intelligence is involved in children from a very early age, i.e. 0-3 years. After the age of 4 heredity predominates markedly over environmental influences up to the age of 15 years investigated so far by the author. (A slight decline occurs during the prepubertal period-age 13 and 14 years.) The author found that in particular the following components of intellect are inborn: abstract thinking, logic, talent for mathematics, concentration, inquisitiveness. Very detailed tables are presented for possible comparison with data in the literature and data from adults. The author found that the development of intelligence from childhood to adult age is very irregular. This uneven character is also mostly inborn. Statistical evaluation revealed several basic types of developmental curves and extreme variants. This will, however, be discussed in another paper. The theoretical results can be used also in practice in school education, counselling psychologic and psychiatric out-patient departments. PMID- 8353831 TI - [Indications for antidepressive agents in relation to diseases of the cardiovascular system]. AB - Antidepressants, in particular tricyclic ones (TCA), and inhibitors of monoaminooxidase (IMAO) exert a number of undesirable cardiovascular effects. TCA and IMAO frequently cause postural hypotension (PH). IMAO administration is associated with the risk of hypertensive crisis. TCA raises the heart rate and can cause abnormalities in the conduction of the cardiac excitation. TCA are contraindicated after myocardial infarction and are the cause of death after overdosage. When PH is undesirable, in hypertension and cardiac insufficiency the following safe antidepressants are recommended: nortriptyline, mianserine, trazodone and viloxazine. In abnormalities of conduction of the cardiac excitation and after myocardial infarction only mianserine, trazodione and viloxazine are recommended. With regard to cardiovascular toxicity, antidepressants from the series of selective inhibitors of serotonin reabsorption are very promising: fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. The same applies also to the reversible IMAO type A moclobemide. PMID- 8353832 TI - [Effects of group psychotherapy]. AB - Using questionnaires SCL 90 and PFI, the author investigated in 1989-1990 the effect of group psychotherapy provided at the psychotherapeutic department of the psychiatric sanatorium in Kromeriz. The group comprised 40 men and 60 women with neurotic complaints. The control group was formed by 45 men and 193 women without neurotic complaints. The questionnaire SCL90 recorded positive changes after group psychotherapy in the therapeutic community, in particular in female patients. A catamnestic examination made after one year, using the same questionnaire, suggests that the therapeutic results have a permanent character. Conversely the PFI questionnaire recorded few significant changes. The problem of assessment of the effect of psychotherapy is discussed also on a more general level. PMID- 8353833 TI - [Memories of psychiatric practice in a North American prison]. PMID- 8353834 TI - Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344 rats. AB - Epidemiologic studies suggest that sustained use of aspirin may reduce the risk of development of and mortality due to colon cancer. Previous preclinical studies have shown that several non-steroidal anti-inflammatory drugs act as potential chemopreventive agents in experimentally induced colon cancer models. The present study was designed to investigate the chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of aspirin administered in the diet on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. The MTD of aspirin as determined in male F344 rats was 500 p.p.m. Beginning at 5 weeks of age, all animals were randomly divided into various experimental groups (48 rats/group) and fed one of the semipurified diets containing 0, 200 p.p.m. (40% MTD), or 400 ppm (80% MTD) of aspirin. Two weeks later, all animals (36 rats/group) except the vehicle-treated groups (12 rats/group) were administered s.c. injections of AOM at a dose level of 15 mg/kg body wt, once weekly for 2 weeks. All animals were continued on their respective dietary regimen for additional 52 weeks and necropsied. Histopathologic evaluation of colon tumors was performed by routine procedures. Basal levels and ex vivo production of colonic mucosal and tumor prostaglandin E2 (PGE2) were measured in all groups. The results indicate that daily oral administration of 200 and 400 p.p.m. aspirin significantly inhibited the incidence (% animals with tumors) and multiplicity (tumors/animal) of invasive adenocarcinomas of the colon as well as the size of adenocarcinomas. Colonic mucosal and tumor PGE2 levels (basal and ex vivo production) were significantly reduced in animals administered 200 and 400 p.p.m. aspirin. The results of this study support the epidemiologic evidence that ingestion of aspirin inhibits colon carcinogenesis. Although the precise mechanisms of aspirin-induced colon tumor inhibition remain to be determined, it is likely that the effect may be mediated through the modulation of prostaglandin synthesis. PMID- 8353835 TI - Depression of catalase gene expression after immortalization and transformation of mouse liver cells. AB - To understand the molecular basis of the remarkable decrease of catalase activity after immortalization and malignant transformation of mouse liver cells, expression of the catalase gene was studied in in vivo mouse liver cells and nontransformed normal mouse liver cell line as well as liver cell lines transformed by N-methyl-N-nitro-N-nitrosoguanidine, SV40 virus or by conventional subcultivation. In vivo liver cells had much greater levels of catalase mRNA and immunoreactive protein than in vitro cell lines, which correlates with elevated enzyme activity. Among the cell lines, normal cells had in general higher mRNA levels and more catalase protein than that of the transformed cell lines, also correlating with enzyme activity. The down regulation of catalase gene expression seen in transformed lines may occur transcriptionally rather than posttranscriptionally as demonstrated by cycloheximide and/or actinomycin D treatment. The striking difference in catalase gene expression seen between liver tissue and liver cell lines was unlikely due to gross structural alterations in the catalase gene, but might be explained by a remarkable difference in methylation status of the catalase gene, as demonstrated by Southern blot analysis following HpaII digestion. Our results suggested that during cellular immortalization and malignant transformation, a change in the oxidant stress ultimately led to a cellular response that, in turn, led to down regulation of the catalase gene. PMID- 8353836 TI - Iterative chromosome mutation and selection as a mechanism of complete transformation of human diploid fibroblasts by SV40 T antigen. AB - The acquisition of an extended lifespan and of neoplastic properties, including anchorage independence, ability to grow in low serum-containing media, morphological transformation, immortalization and tumorigenicity in nude mice were studied in 31 human fibroblast lineages transfected with plasmids containing the SV40 early genes. Plasmids were used that contained sequences for large T alone, or large T plus small t or large T plus small t plus the SV40 origin. Cells expressing large T antigen gradually acquired the ability to form colonies in low serum or to form anchorage-independent colonies. Large T antigen was sufficient to cause complete transformation to tumorigenicity if multi-step lineage evolution was obtained by prolonged serial passage and if in vivo progression was assisted by means of a gelatin sponge implantation technique. Cells derived from progressive tumors initiated in sponges showed enhanced tumorigenicity as measured by ability to obtain tumors without using sponges and with reduced latent period, higher incidence and with fewer cells inoculated. Multiple lineages of human fibroblasts have been converted to tumorigenicity without additional treatments such as transfection with activated oncogenes or exposure to carcinogens. These data, taken in conjunction with earlier studies showing that T antigen causes chromosome mutation preceding and accompanying the accumulation of the neoplastic phenotype, suggests that the T protein drives the transformation process by acting as a mutagen and cells with growth advantages were selected for in vitro and in vivo. With the possible exception of morphological transformation, the presence or absence of genes for small t and the SV40 origin were not critical for the process. PMID- 8353837 TI - A new in vivo model for studying invasion and metastasis of rat and human bladder carcinomas. AB - The biological potential of tumor cells is best evaluated at the organ site orthotopic to the tumor cells. Recent studies have documented site-specific differences in the potential of tumor cell growth. However, orthotopic implantation of bladder cancer cells into bladders of nude mice only resulted in a low tumor yield. We have developed a new model that consists of a rat bladder transplanted into the retroperitoneal space and connected to a reservoir s.c. placed in a nude mouse. Rat malignant bladder cancer cells (MYU3L and LMC19) transfected with the human growth hormone (hGH) gene as a biomarker were introduced into the transplanted bladder by percutaneous puncture of the attached reservoir. Successful uptake was indicated by a progressive rise in the hGH level in the bladder aspirate. When examined at 6-16 weeks post transplantation, all mice that had received MYU3L (n = 6) or LMC19 (n = 6) cells were found to have invasive carcinomas. MYU3L was highly invasive, forming multiple peritoneal implants, but was not metastatic. LMC19 was deeply invasive and metastasized to the retroperitoneal and subclavian lymph nodes and the lungs (4/6). Of two human bladder cancer cell lines (RT4 and T24) tested, RT4 formed multiple minute papillary tumors in five of six bladders, two of which were minimally invasive to the muscle layer. T24 cells formed only one to two small tumors in three of six bladders, and these were confined to the lamina propria. This system appears promising for studies of the mechanism of tumor invasion and metastasis and for evaluation of antineoplastic agents. PMID- 8353838 TI - Brain and liver targeted overexpression of O6-methylguanine DNA methyltransferase in transgenic mice. AB - O6-Methylguanine DNA methyltransferase (MGMT; EC 2.1.1.63) is an unusual DNA repair protein in that it directly and specifically repairs a premutagenic DNA lesion without involving other proteins. MGMT removes the alkyl group from O6 alkylguanine in DNA in a unique stoichiometric reaction by accepting the alkyl group on a cysteine residue. The intracellular level of MGMT varies among tissues and appears to be inversely correlated to tissue-specific tumorigenesis induced by monofunctional alkylating agents. Because MGMT acts in solo, genetic manipulation of its expression may provide valuable insight into its contribution to cellular resistance to alkylation toxicity and to tumor induction. The human MGMT full length cDNA has been fused with a portion of the human transferrin (TF) 5'-flanking region (TF/MGMT). Transgenic founder mice were produced carrying the TF/MGMT transgene and then bred to establish stable transgenic lines. Human MGMT transcripts were specifically expressed in abundance in transgenic brain and liver tissues. In vitro MGMT assays revealed approximately 150-fold and approximately 25-fold increases in MGMT activity in transgenic brain and liver extracts respectively. Western blot analysis confirmed that human MGMT protein is specifically synthesized in transgenic brain and liver tissues. PMID- 8353839 TI - Comparison of transplacental and neonatal initiation of mouse lung and liver tumors by N-nitrosodimethylamine (NDMA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) and promotability by a polychlorinated biphenyls mixture (Aroclor 1254). AB - We have previously shown a positive tumor-promoting effect of a single dose of Aroclor 1254 on lung and liver tumors initiated neonatally in the mouse by N nitrosodimethylamine (NDMA). In this study, we have confirmed and extended this observation with NDMA and the tobacco-specific nitrosamine, 4-(methylnitrosamino) 1-(3-pyridyl)-1-butanone (NNK) given either transplacentally or postnatally, followed by a single dose of Aroclor 1254 on day 56. This polychlorinated biphenyl (PCB) mixture was an effective promoter of both lung and liver tumors; however, there were specific initiator and sex-related differences in this response. Aroclor administration significantly increased the incidence of lung tumors initiated transplacentally by NDMA or NNK in male mice. Neither nitrosamine initiated tumors transplacentally in females, but lung tumors initiated with NNK and liver tumors caused by NDMA in neonatal females were promoted by PCBs. Both liver and lung tumors initiated neonatally by NDMA in male animals, but not NNK-initiated tumors, were promoted by PCBs. These data confirm that PCBs are able to promote both NDMA- and NNK-initiated tumors, but with chemical-, sex- and age-dependent difference; this suggests influences of both quantitative and qualitative factors in susceptibility to tumor promotion. PMID- 8353840 TI - Effects of green tea catechins in a rat multi-organ carcinogenesis model. AB - The effects of dietary administration of green tea catechins (GTC) were examined using a multi-organ carcinogenesis model. Groups of 15 F344 male rats were initially treated with a single i.p. administration of 100 mg/kg body wt N diethyl-nitrosamine, 4 i.p. administrations of 20 mg/kg body wt N methylnitrosourea, 4 s.c. doses of 40 mg/kg body wt 1,2-dimethylhydrazine, together with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine for 2 weeks and then 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine for 2 weeks, both in the drinking water, for a total initiation period of 4 weeks. GTC in the diet, at doses of 1.0 or 0.1%, was administered from 1 day before and during carcinogen exposure, after carcinogen exposure or both during and after carcinogen exposure. Further groups of animals were treated with carcinogen, 1% GTC or basal diet alone as controls. All animals were killed at the end of week 36, and all major organs examined histopathologically. The numbers of small intestinal tumors (adenomas and carcinomas) per rat were significantly reduced in the groups treated with 1% GTC during (0.13 +/- 0.35) and after carcinogen exposure (0.31 +/- 0.48) and in those receiving 1% and 0.1% GTC both during and after carcinogen exposure (0.14 +/- 0.36, 0.46 +/- 0.97 respectively) as compared with the carcinogen alone group (1.07 +/- 1.21). On the other hand, numbers of glutathione S-transferase placental form positive liver foci per cm2 were slightly but significantly increased in the groups treated with 1 and 0.1% GTC during carcinogen exposure, 1% GTC after carcinogen exposure and 1% GTC both during and after carcinogen exposure. The results indicated that while GTC inhibits small intestinal carcinogenesis it slightly enhances hepatocarcinogenesis in a dose dependent manner when applied both during and after carcinogen exposure. PMID- 8353841 TI - N-methyl-N'-nitro-N-nitrosoguanidine-induced carcinogenesis: differential pattern of upper gastrointestinal tract tumours in Wistar rats after single or chronic oral doses. AB - Male Wistar rats were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) either as a single dose of 50, 125 or 250 mg/kg given by gavage or via drinking water for 28 weeks at a concentration of 40, 80 or 160 micrograms/ml, in the case of the higher concentration reverting to 80 micrograms/ml after the first 8 weeks. The single dose regimen had no effect on water intake or body weight, but the chronic exposure led to a dose-dependent reduction in water intake that was paralleled by a slower weight gain, with the final body weights at approximately 90, 84 and 79% of the control weight values. The combined yield of benign and malignant tumours (79-100% of the animals treated) occurred in the forestomach in the case of the single doses, whereas the chronic exposure resulted in a maximum yield of tumours located in the pyloric region of the glandular stomach (64-100% of animals treated). The principal histological types of tumours induced were squamous cell papilloma and carcinoma in the forestomach and adenocarcinoma in the pylorus. There was a persistent, but low yield (25-30% of animals treated) of tumours in the jejunum, mainly adenocarcinoma, after administration via drinking water, whereas after single doses, multiple solitary cysts and cholangioma (30% and 25-70% respectively of the animals treated) were found in the liver. This report differs from earlier reports in that marked effects were noted on water consumption and body weight gain and that tumour induction can be achieved after much shorter periods of exposure than previously reported in the literature. These data confirm the tissue specificity of MNNG when given either as a single or chronic dose regimen and provide a suitable model for the investigation of the target cell specificity of tumour induction. PMID- 8353842 TI - Cyclosporine stimulates hepatocyte proliferation and accelerates development of hepatocellular carcinomas in rats. AB - A recent study from our laboratory demonstrated that cyclosporine (CsA), a prototype immunosuppressant, enhanced the growth of carcinogen-induced enzyme altered foci in rat liver, suggesting that CsA may stimulate development of hepatocellular carcinomas. In the present study, we examined (i) whether CsA accelerates development of hepatocellular carcinomas in experimental animals, (ii) whether CsA stimulates the proliferation of resting hepatocyte in vivo and (iii) whether CsA modulates the production of growth factors implicated in liver cell growth, hepatocyte growth factor (HGF), transforming growth factor alpha (TGF alpha) and transforming growth factor beta 1 (TGF beta 1). Foci of hepatocytes, positive for glutathione S-transferase placental form were induced in male F344 rats by a single dose of diethylnitrosamine followed by 7 weeks promotion by a choline-deficient diet. The animals were then divided in two groups, and subsequent development of hepatocellular carcinomas was compared in rats fed a basal diet or a basal diet containing 0.015% CsA. Development of hepatocellular carcinoma was accelerated in the rats maintained on a CsA diet. Feeding a CsA diet as the sole treatment, for 2, 4 and 10 weeks induced significant increases in liver weight, and resulted also in an enhanced incorporation by hepatocytes of 5-bromo-2-deoxy-uridine. Serum levels of glutamate-oxaloacetate transferase, glutamate-pyruvate transferase and lactic dehydrogenase were not altered by feeding a CsA diet. Northern Blot analyses of the expression of HGF, TGF alpha and TGF beta 1 mRNAs in the liver showed similar patterns of expression between rats fed a basal diet and a CsA diet. The levels of HGF mRNA were not altered in the lungs and kidneys of rats fed a CsA diet. These results indicate that CsA stimulates rat liver cell proliferation in vivo without inducing liver cell necrosis, and that this effect may contribute to accelerated development of hepatocellular carcinomas in rats fed a CsA diet. As previously observed with BR 931, a hypolipidemic peroxisome proliferator, stimulation of liver cell growth by CsA did not entail changes in the production of HGF, TGF alpha or TGF beta 1. PMID- 8353843 TI - Repair of ribosomal RNA genes in hamster cells after UV irradiation, or treatment with cisplatin or alkylating agents. AB - We have measured the DNA damage formation and repair in the ribosomal and the dihydrofolate reductase (DHFR) genes after treatment of hamster cells with different types of DNA damaging agents. In mammalian cells, the ribosomal DNA (rDNA) is transcribed by RNA polymerase I, whereas the DHFR is transcribed by RNA polymerase II, whereas the DHFR is transcribed by RNA polymerase II. Cells were treated with agents that induce different types of lesions, and that are known to be repaired via different pathways. We used UV (254 nm) irradiation, treatment with cisplatin and treatment with the alkylating agents nitrogen mustard (HN2) and methyl methanesulphonate (MMS). UV induced pyrimidine dimers were detected with the enzyme T4 endonuclease V, which creates nicks at the dimer sites; the breaks are then resolved and identified by denaturing electrophoresis and Southern blot. Intrastrand adducts formed by the alkylating agents HN2 and MMS were quantitated by generating strand breaks at abasic sites after neutral depurination. Interstrand crosslinks (ICL) formed by HN2 and cisplatin were detected by a denaturation-reannealing reaction before neutral agarose gel electrophoresis. We find that the repair of the pyrimidine dimers is significantly less efficient in the RNA polymerase I transcribed rDNA genes than in RNA polymerase II transcribed DHFR gene at 8 and 24 h after irradiation. ICL and intrastrand adducts induced by HN2 are also removed more slowly from the rDNA than from the DHFR gene. In contrast, MMS induced intrastrand adducts and cisplatin induced ICL are repaired equally efficiently in the RNA polymerase I and RNA polymerase II transcribed genes. We conclude that for some types of DNA damage, there is less repair in the ribosomal genes than in the DHFR; but for other DNA lesions there is no difference. The difference in repair efficiency between the rDNA and the DHFR genes may reflect the different RNA polymerase involved in their transcription. It may, however, alternatively, reflect the different nuclear localization of these genes. PMID- 8353844 TI - Dose-dependent ras mutation spectra in N-nitrosodiethylamine induced mouse liver tumors and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced mouse lung tumors. AB - In a previous study, the spectrum of H-ras mutations detected in B6C3F1 mouse liver tumors induced by 5, 50 or 150 mumol/kg body wt of N-nitrosodiethylamine (NDEA) was similar to that in spontaneous B6C3F1 mouse liver tumors, suggesting that activation of the H-ras gene in NDEA-induced mouse liver tumors may not be the direct result of the chemical interaction with the H-ras gene. In the present study, mutations in the H-ras oncogene from B6C3F1 mouse liver tumors induced by 5 or 50 mumol/kg body wt of NDEA were characterized by DNA amplification with polymerase chain reaction (PCR), single-strand conformation of polymorphism (SSCP) and direct sequence analysis. Twenty-one of 66 NDEA-induced B6C3F1 mouse liver tumors contained activated H-ras gene with 2 of 21 having a CG to AT transversion at the first base of codon 61, 17 of 21 having AT to GC transition and 2 of 21 having an AT to TA transversion at the second base of codon 61 in the H-ras gene. The predominant mutation, AT to GC transition (17/21, 81%) is consistent with the formation of O4-ethylthymine adduct, and is distinct from the predominant CG to AT transversion (50%) at the first base of codon 61 detected in H-ras gene from NDEA-induced B6C3F1 mouse liver tumors in a previous study by Stowers et al. Mutations in the K-ras oncogene from 59 A/J mouse lung tumors induced by 0.53 mmol/kg body wt of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were also characterized by using the above mentioned methods. Forty-six of 59 NNK-induced A/J mouse lung tumors contained activated K-ras genes. All 46 (100%) of the activated K-ras gene had GC to AT transitions at the second base of codon 12. The same mutation was observed in 70% (7/10) of the K-ras oncogene from A/J lung tumors induced by 4.8 mmol/kg body wt (given in 21 doses) of NNK. These data suggest that other factors in addition to genotoxic effect might be involved in the induction of rodent tumors by some carcinogens when given at higher doses. Therefore, further studies to compare the dose-dependent differences in the profile of ras mutations induced by chemical carcinogens may help to assess human cancer risk. Mutation(s) in exons 5-8 of the p53 gene was not found in these NDEA induced mouse liver tumors and NNK-induced mouse lung tumors. PMID- 8353845 TI - High mutagenic activity of N-nitrosobis(2-oxopropyl)amine and N-nitrosobis(2 hydroxypropyl)amine in the host-mediated assay in hamsters: evidence for premutagenic methyl and hydroxylpropyl adducts. AB - The carcinogenic nitrosamines N-nitrosobis(2-oxopropyl)-amine (BOP) and N nitrosobis(2-hydroxypropyl)amine (BHP) were tested in excision-repair-deficient strains of hisG46 Salmonella mutants in the intrasanguinous host-mediated mutagenesis assay (HMA) in male Syrian hamsters. The major adducts produced by BOP in the hamster are methylguanines, while BHP leads to hydroxypropylguanines as well as methylguanines. Both nitrosamines were potent mutagens in bacteria recovered from the liver. On a comparison of administered dose, BOP was more potent, but when compared at doses producing similar levels of O6-methylguanine (O6-MeG) in host liver DNA, or at equitoxic doses in the hamster, BHP was more potent. BHP was approximately 10 times less mutagenic in an excision-repair proficient strain of Salmonella, but the mutagenicity of BOP was not reduced. The effects of excision repair on in vitro mutagenesis induced by the direct-acting analogs N-(2-oxopropyl)-N-nitrosourea (OPNU), a methylating agent, and N-(2 hydroxypropyl)-N-nitrosourea (HPNU), a hydroxypropylating agent, were also examined. Mutagenesis by HPNU, but not OPNU was very sensitive to excision repair. Thus BOP appears to lead to mutagenesis via methylation, while mutagenesis by BHP apparently proceeds via hydroxypropylation. BOP, BHP, OPNU and HPNU were several times less mutagenic in hisG428 than hisG46 strains. In contrast to hisG46 strains, which are reverted mainly by base-pair substitutions at G:C base pairs, hisG428 strains are generally more sensitive to mutagenesis at A:T base pairs. Taken together the above results and observations that > 90% of the adducts from BOP and BHP were alkylguanines, suggest that the major premutagenic adducts produced from BOP and BHP are alkylguanines as opposed to other alkylated bases. BOP and BHP were weak mutagens in the Salmonella/S-9 mutagenesis assay using hamster liver S-9 fraction. When compared with results in the HMA, BOP and BHP were orders of magnitude less mutagenic in vitro. This observation suggests: (i) the pathways or enzymes involved in the activation of these carcinogens (although uncertain) may be different in vivo and in vitro; or (ii) the pathways for the in vitro and in vivo metabolism may be similar, but the conditions used for the in vitro activation of these nitrosamines are inadequate to generate significant levels of nitrosamine metabolites. PMID- 8353846 TI - Impact of various sources of garlic and their constituents on 7,12 dimethylbenz[a]anthracene binding to mammary cell DNA. AB - The present studies assessed the impact of various sources of garlic and their constituents (water- and ethanol-extracts and S-allylcysteine) on the in vivo binding of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) to rat mammary cell DNA. The provision of dietary raw garlic powder (2%) or its water-extract (1.5%) reduced DMBA-DNA binding by 33 and 46% respectively. Dietary supplementation with a commercially available deodorized garlic powder (powder A) at 2 or 4% depressed the occurrence of adducts by 50 and 78% respectively, while providing a commercially available high sulfur garlic preparation (powder B) at 2% reduced binding by 56%. A pair-feeding study revealed that the depression in carcinogen binding was independent of food intake or weight gain. Although 1% raw garlic powder did not significantly influence the occurrence of DMBA-DNA adducts, an equivalent as the water-extract (0.75%), the ethanol-extract (0.015%) or commercially available powders (A and B) reduced DMBA adducts in mammary tissue by 44, 25, 71 and 65% respectively. Dietary fortification with S-allylcysteine (SAC), a water-soluble constituent of processed garlic, caused a progressive decrease in the binding of DMBA to DNA. Studies with SAC suggest the primary effect of garlic and its constituents is on the bioactivation and binding of the carcinogen rather than DNA repair. These data reveal that several forms of garlic are effective, although variable, in altering carcinogen bioactivation and presumably chemically induced carcinogenesis. PMID- 8353847 TI - Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. AB - A genetic polymorphism at the NAT2 gene locus, encoding for polymorphic N acetyltransferase (NAT2), segregates individuals into rapid, intermediate or slow acetylator phenotypes. Both rapid and slow acetylator phenotypes have been associated with increased incidence of cancer in certain target organs related to arylamine exposure, suggesting a role for acetylation in both the activation and deactivation of arylamine carcinogens. A second gene (NAT1) encodes for a different acetyltransferase isozyme (NAT1) that is not subject to the classical acetylation polymorphism. In order to assess the relative ability of NAT1 and NAT2 to activate and deactivate arylamine carcinogens, we tested the capacity of recombinant human NAT1 and NAT2, expressed in Escherichia coli XA90 strains DMG100 and DMG200 respectively, to catalyze the N-acetylation (deactivation) and O-acetylation (activation) of a variety of carbocyclic and heterocyclic arylamine carcinogens. Both NAT1 and NAT2 catalyzed the N-acetylation of each of the 17 arylamines tested. Rates of N-acetylation by NAT1 and NAT2 were considerably lower for heterocyclic arylamines such as 2-amino-3-methyl-imidazo[4,5 f]quinoline (IQ), particularly those (e.g. IQ) with steric hindrance to the exocyclic amino group. For carbocyclic arylamines such as 4-aminobiphenyl and beta-naphthylamine, the apparent affinity was significantly (P < 0.05) higher for NAT2 than NAT1. NAT1/NAT2 activity ratios and clearance calculations suggest a significant role for the polymorphic NAT2 in the N-acetylation of carbocyclic arylamine carcinogens. Both NAT1 and NAT2 catalyzed acetyl coenzyme A-dependent O acetylation of N-hydroxy-2-aminofluorene and N-hydroxy-4-aminobiphenyl to yield DNA adducts. NAT1 catalyzed paraoxon-resistant, intramolecular N,O acetyltransferase-mediated activation of N-hydroxy-2-acetylaminofluorene and N hydroxy-4-acetylaminobiphenyl at low rates; catalysis by NAT2 was not readily detectable in the presence of paraoxon. In summary these studies strongly suggest that the human acetylation polymorphism influences both the metabolic activation (O-acetylation) and deactivation (N-acetylation) of arylamine carcinogens via polymorphic expression of NAT2. These findings lend mechanistic support for human epidemiological studies suggesting associations between both rapid and slow acetylator phenotype and cancers related to arylamine exposure. PMID- 8353848 TI - Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human kidney epithelial cells transfected with rat CYP2B1 cDNA. AB - In all species where it has been tested, the tobacco-specific nitrosamine 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) has been shown to be a potent carcinogen, and NNK and other nitrosamines may play a role in human tobacco related carcinogenesis. Purified rat CYP2B1 has been shown to metabolize NNK, and the CYP2B1 gene is expressed constitutively in rat lung. The objectives of this study were to test the capacity of CYP2B1, synthesized from a rat hepatic cDNA in Ad293 cells, to metabolize NNK, and to define the type and the proportions of the final metabolites produced. Ad293 cells were transfected with a CYP2B1 expression vector (pMT2-2B1), or with a control vector and incubated in culture medium containing [3H]NNK, after which alpha-carbon hydroxylation and pyridine N oxidation metabolites were identified by HPLC analysis and quantitated by scintillation counting. pMT2-2B1-transfected cells were capable of catalyzing alpha-carbon hydroxylation and pyridine N-oxidation of NNK, although the reduction product 4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol(NNAL) was the major metabolite formed in cells regardless of transfection treatment. The total amount of alpha-carbon hydroxylation metabolites produced by pMT2-2B1-transfected cells was greater than that of pyridine N-oxidation metabolites. However, pMT2 2B1 transfected cells produced approximately ten-fold more pyridine N-oxidation metabolites and only two-fold more alpha-carbon hydroxylation metabolites than control cells. Furthermore, the amount of NNAL-N-oxide was much lower than that of NNK-N-oxide in the medium of pMT2-2B1-transfected cells, even though the amount of available NNAL, resulting from carbonyl reduction of NNK, was very high; this suggests that NNAL is poorly N-oxidized by CYP2B1 compared to NNK. These results show that within living cells NNK was metabolized by CYP2B1 via both the pyridine N-oxidation and alpha-carbon hydroxylation pathways. However, CYP2B1 preferentially catalyzed pyridine N-oxidation, which is considered to be a deactivation reaction. PMID- 8353849 TI - Expression of human cytochrome P450 1A1 in DNA repair deficient and proficient human fibroblasts stably transformed with an inducible expression vector. AB - Cytochromes P450 catalyze the bioactivation of many carcinogens. In particular, cytochrome P450 1A1 (CYP1A1) catalyzes the conversion of polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, into potent mutagenic agents. Human skin fibroblasts, both DNA repair deficient (xeroderma pigmentosum group A: XPA) and DNA repair normal have been co-transformed with a chimeric gene construct containing human CYP1A1 coding sequences controlled by the cadmium (Cd) ion inducible mouse metallothionein-I promoter and pRSV-NEO, a dominant selectable marker for G418 resistance. Individual G418 resistant colonies were cloned and analyzed for Cd inducible CYP1A1 activity. Six clones of DNA repair deficient cells and five clones of DNA repair proficient cells have been isolated which express Cd inducible CYP1A1. Benzo[a]pyrene-trans-7,8-diol (BPD) is cytotoxic in Cd induced CYP1A1 expressing cells. The cytotoxicity can be inhibited by 10 microM alpha-napthoflavone. Differential cytotoxicity between the DNA repair deficient and proficient CYP1A1 expressing transformants is observed. BPD is cytotoxic to Cd induced CYP1A1 expressing XPA cells at > 10-fold lower doses than it is to Cd induced CYP1A1 expressing DNA repair normal cells. These data indicate that BPD is metabolized to a DNA damaging agent by induced CYP1A1. In contrast, benzo[a]pyrene-trans-7,8-diol-9,10-epoxide added to the media is only slightly more cytotoxic to DNA repair deficient than to proficient cells regardless of CYP1A1 expression. These studies demonstrate the usefulness of the CYP1A1 transformed fibroblasts in examining the cytotoxic effects of benzo[a]pyrene metabolites and suggest the future usefulness in examining the toxic effects of polycyclic aromatic hydrocarbons and other xenobiotics bioactivated by CYP1A1. PMID- 8353850 TI - Bioactivation of N-hydroxy-2-acetylaminofluorenes by N,O-acyltransferase: substituent effects on covalent binding to DNA. AB - N-Acetoxyarylamines are reactive metabolites that lead to arylamine adduct formation with biological macromolecules. A series of 7-substituted-N-hydroxy-2 acetylaminofluorenes were converted to reactive N-acetoxyarylamines by enzymatic N,O-acyltransfer in the presence of DNA. The N-arylhydroxamic acid substrates that contained electronegative 7-substituents formed greater amounts of DNA adducts than either the unsubstituted compound (N-OH-AAF) or those analogs that contained electron-donating groups in the 7-position. Glutathione did not decrease the rates of DNA adduct formation, but other nucleophiles, such as potassium O-ethylxanthate, thiourea and N-acetylmethionine, inhibited adduct formation by the 7-Br-substituted compound (7-Br-N-OH-AAF) and the unsubstituted parent compound (N-OH-AAF). Nucleophiles, reducing agents (e.g. ascorbic acid) and spin-trapping agents had minimal effect on DNA adduct formation by the bioactivated form of 7-acetyl-2-(N-hydroxy-acetylamino)fluorene (7-Ac-N-OH-AAF). Triethylphosphite, an agent that reacts with aryl nitrenes, caused a concentration-dependent reduction in the amount of DNA adduct formed subsequent to bioactivation of 7-Ac-N-OH-AAF, but did not influence adduct formation when N OH-AAF and 7-Br-N-OH-AAF were the substrates. The results indicate that a change in the reaction mechanism(s) responsible for DNA adduct formation occurred when the strongly electronegative acetyl group was incorporated into the 7-position of N-OH-AAF. It is proposed that a nitrene intermediate is involved in the formation of covalent adducts with DNA when 7-Ac-N-OH-AAF is activated by N,O-acyltransfer. PMID- 8353851 TI - Demonstration of a 65 kDa tumor-specific phosphoprotein in urine and serum of rats with N-methyl-N-nitrosourea-induced mammary adenocarcinomas. AB - Polyclonal antibodies against a 65 kDa tumor-associated phosphoprotein (p65) were used to develop an ELISA to analyze the presence of p65 in urine and serum of rats bearing N-methyl-N-nitrosourea-induced mammary gland adenocarcinomas. Highly purified rat p65 was added to normal urine and serum to establish a quantitative standard curve with the average correlation coefficient being 0.98 and 0.99 respectively. All samples of urine and serum obtained from different carcinoma bearing rats showed p65 concentrations above the normal levels found in the control urine and sera. The correlation coefficient between tumor burden and p65 concentration in urine and serum was 0.65 and 0.77 respectively. The average levels of p65 in normal urine and normal serum were 37.0 +/- 32.0 and 48.0 +/- 38.0 ng/ml respectively. In the case of urine obtained from rats bearing mammary adenocarcinomas, the mean p65 level was 119.0 +/- 35.9 ng/ml and their serum level was 225.4 +/- 67.5 ng/ml. Sensitivity, specificity and predictive value for serum and urine marker elevation were 78.5, 70.0 and 78.5% respectively. Following in vitro phosphorylation of concentrated urinary proteins, isoelectrofocusing, SDS-PAGE and autoradiography, a phosphorylated form of the 65 kDa protein with a pI of 5.8 was identified in the urine of tumor-bearing rats. This phosphoprotein bound to an antiphosphotyrosine monoclonal antibody and an anti-p65 polyclonal as determined by Western blot analysis. Using the anti-p65 antibodies in an immunoprecipitation procedure, the main radio- and immunoactive band of 65 kDa and two lower mol. wt bands of 50 and 41 kDa, apparently representing degradation products of p65, were identified after in vitro and in vivo phosphorylation of urinary proteins obtained from mammary carcinoma-bearing rats. PMID- 8353852 TI - Transgenic Drosophila carrying mammalian cytochrome P-4501A1: an application to toxicology testing. AB - Transgenic Drosophila which carry a canine cytochrome P-450 were established and evaluated for its value on toxicology testing. Dah1, a cDNA clone for the canine hepatic P-4501A1, was ligated between the promoter of Drosophila heat-shock protein gene and the terminator of actin 5C gene, and then microinjected into Drosophila embryos with a transposon P element. The injected DNA was stably integrated into chromosomal DNA in germ line cells. After heat-shock treatments, transgenic larvae produced mRNA and a detectable amount of protein that cross reacted with antibodies against rat P-4501A1. The ability of transgenic flies to activate procarcinogens was monitored in the DNA repair test with the endpoint being preadult mortality of repair-defective mei-9a mei-41D5/Y males. Heat-shock treatments of larvae showed that the repair-defective males carrying the P-4501A1 transgene were killed by lower concentrations of 7,12-dimethylbenz[a]anthracene than their non-transgenic or non heat-shocked counterparts. Coadministration of alpha-naphthoflavone, one of the inhibitors of P-4501A subfamily, cancelled the enhanced mortality of transgenic males, supporting that 7,12 dimethylbenz[a]anthracene was metabolized to its genotoxic form by the expressed P-4501A1 enzyme. This study indicates a potential utility of transgenic Drosophila for screening mammalian promutagens and procarcinogens. PMID- 8353853 TI - The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats. AB - Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit. PMID- 8353854 TI - The in vitro metabolic activation of the 11-trifluoromethyl analogue of the potent carcinogen 15,16-dihydro-11-methyl-cyclopenta[a]-phenanthren-17-one to mutagens. AB - A strongly electronegative, bay-region analogue of the potent carcinogen 15,16 dihydro-11-methylcyclopenta[a]phenanthren-17-one, namely 15,16-dihydro-11 trifluoromethylcyclopenta[a]phenanthren-17-one, is mutagenic to Salmonella typhimurium TA100. Also it is metabolized at the 1,2- and 3,4-positions in the A ring as well as C-15 in the D-ring to give 3,4-dihydroxy-3,4,15,16-tetrahydro-11 trifluoromethyl- cyclopenta[a]phenanthren-17-one as the only mutagenic metabolite. In these respects its behaviour is closely similar to that of the 11 methyl compound, suggesting that the electronic nature of the bay-region substituent is rather less critical than its spatial configuration in influencing metabolism to genotoxic intermediates. It remains to be seen, however, whether the trifluoromethyl compound is also a carcinogen. PMID- 8353855 TI - Increasing the interval between initiation and the onset of exposure to orotic acid decreases its promoting effect on rat liver carcinogenesis. AB - The present study was designed to determine whether a delay in the start of the promoting regimen after the administration of a carcinogen would influence the promoting efficacy of orotic acid on the development of hepatocellular carcinoma in rats. Male Fischer 344 rats weighing 130-150 g were injected with a single dose of diethylnitrosamine (200 mg/kg body wt i.p.) then divided into 3 groups: groups 1 and 2 were given semi-synthetic basal diet or the same diet containing 1% orotic acid (OA) respectively starting 1 week after the carcinogen; group 3 received the OA diet starting 5 weeks after the administration of diethylnitrosamine. Animals from these 3 groups were sacrificed after 25, 32, 42 and 60 weeks of being fed their respective diets. The results indicated that delaying the start of the OA diet after the carcinogen resulted in about a 50% decrease in the incidence of hepatic nodules and/or hepatocellular carcinomas at various time points during the experiment. This decrease in promoting efficacy of OA was not apparently explainable by lack of metabolic effects of OA, at least in terms of induction of nucleotide pool imbalance, a condition that appears to be important for OA to exert its tumor promoting effects. PMID- 8353856 TI - Metabolism and activation of pancreas specific nitrosamines by pancreatic ductal cells in culture. AB - Metabolism of 14C labeled N-nitrosobis(2-oxopropyl)amine (BOP), N-nitroso(2 hydroxypropyl)(2-oxopropyl)amine (HPOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP) by pancreatic duct cells in culture involves the following two pathways: reduction or oxidation reactions at the beta-carbon which result in the inter conversion of these nitrosamines and activation reactions which result in the decomposition of the nitrosamine, the evolution of 14CO2 and the labeling of macromolecules. Reduction of BOP to HPOP seems to contribute significantly to the metabolism of the former nitrosamine by pancreatic duct cells, however, redox reactions at the beta-carbon of HPOP or BHP are not extensive. In terms of DNA damage, all three nitrosamines yield methyl and hydroxypropyl adducts. As expected, HPOP and BHP yield higher levels of O6-hydroxypropylguanine than BOP, while the latter yields higher levels of O6-methylguanine. There is no correlation between the ability of these nitrosamines to alkylate duct cell DNA in vitro and their carcinogenic potency in vivo. Concentrations of DNA adducts induced by pancreas specific nitrosamines (PSNs) in cultured duct cells at concentrations comparable to those found in the pancreatic juice of animals treated with BOP, are almost an order of magnitude lower than those induced in the pancreas of such animals. Discrepancies between in vitro and in vivo formation of active metabolites and DNA adducts may be attributed to the decline of the cells' ability to activate PSNs during culturing. In the same vein, the ductal cell may not be the main source of active metabolites targeting its DNA in the animal model. PMID- 8353857 TI - Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone mouse lung tumorigenesis by arylalkynes, mechanism-based inactivators of cytochrome P450. AB - Arylalkynes such as 4-phenyl-1-butyne (PBY), 5-phenyl-1-pentyne (PPY) and 2 ethynylnaphthalene (2-EN) are suicide inhibitors of cytochrome P450 enzymes. Arylalkyl isothiocyanates such as 6-phenylhexyl isothiocyanate (PHITC) are structurally related to arylalkynes and are known to inhibit the cytochrome P450 mediated metabolic activation and tumorigenicity of a tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In this study, we compared the ability of PBY, PPY, 2-EN and PHITC to inhibit A/J mouse lung tumorigenesis by NNK. Groups of 20 female mice were gavaged with 5 mumol of arylalkyne or PHITC in corn oil. Two hours later they were given a single i.p. injection of 10 mumol NNK. The mice were killed 16 weeks later. PPY and PHITC were both potent inhibitors of tumorigenesis by NNK, reducing lung tumor multiplicity from 8.35 tumors per mouse to 0.40 and 0.35 respectively. PBY and 2 EN also significantly inhibited tumor multiplicity. The results of this study demonstrate that arylalkynes and PHITC are potent inhibitors of NNK induced lung tumorigenesis in A/J mice, consistent with the hypothesis that inhibition of specific cytochrome P450 enzymes is involved in inhibition of tumorigenesis. PMID- 8353858 TI - Complementary tumor induction in neural grafts exposed to N-ethyl-N-nitrosourea and an activated myc gene. AB - Using a combination of transplacental carcinogen exposure and retrovirus-mediated oncogene transfer into fetal brain transplants, we have studied complementary transformation by N-ethyl-N-nitrosourea (NEU) and the v-myc oncogene in the nervous system. Previous experiments had demonstrated that both agents will not induce tumors independently whereas simultaneous expression of v-H-ras and v gag/myc exerted a powerful transforming potential in neural grafts. In order to identify other genetic alterations that co-operate with an activated myc gene, the neurotropic carcinogen NEU was used to generate mutations of cellular genes. On embryonic day 14 (ED14), pregnant donor animals (F344 rats) received a single i.v. dose of NEU (50 mg/kg). Twenty-four hours later (ED15), the fetal brains were removed, triturated and incubated with a retroviral vector carrying the v gag/myc oncogene. Subsequently, these primary cell suspensions were transplanted stereotactically into the caudate-putamen of syngenic adult recipients. After latency periods of 3-6 months, 5 of 10 recipients harboring ED15 fetal brain transplants developed malignant, poorly differentiated neuroectodermal tumors in the grafts. No tumor development was observed in seven recipients harboring ED16 neural grafts. Cell lines were established from three tumors and the 110 kd gag/myc fusion protein encoded by the retroviral construct was identified in the tumors by Western blotting. Several candidate genes for mutational activation by NEU including the H-ras, K-ras and neu oncogenes were analyzed for specific point mutations by polymerase chain reaction (PCR) and direct DNA sequencing of the PCR products. However, no mutations were found in any of these genes. These findings lend further support to the multistep hypothesis of neoplastic transformation in the brain. The tumors induced in this model provide an interesting tool for the identification of genes that co-operate with an activated myc gene in neurocarcinogenesis. PMID- 8353859 TI - The synthetic colon peptide pyroGlu-His-GlyOH inhibits growth of human colon carcinoma cells (HT-29) transplanted subcutaneously into athymic mice. AB - Growth inhibitory tripeptide, pyroGlu-His-GlyOH colon mitosis inhibitor (CMI), was recently isolated from water extracts of mouse intestine. In the present study, it was demonstrated in two different experiments that i.p. injections of CMI, daily or 3 times a week, could inhibit the long-term s.c. growth of HT-29 cells in athymic mice. The growth inhibitory effect was most pronounced initially with approximately 50-90% growth inhibition, and declined terminally with approximately 40-60% growth inhibition. A bell-shaped dose-response curve with maximal effect at 1 pmol/animal/injection was seen. PMID- 8353860 TI - Lack of initiating capacity of the genotoxic air pollutant 2-nitrofluorene in the mouse skin two-stage carcinogenesis system. AB - 2-Nitrofluorene (NF) is a potent genotoxic substance found in environments where incomplete combustion takes place. NF is a mutagen and a carcinogen in animal models. NF or 7,12-dimethylbenz[a]anthracene (DMBA) was administered once topically to female SENCAR mice followed by promotion by 12-O tetradecanoylphorbol-13-acetate (TPA) in two different studies. TPA (2-5 micrograms) was administered twice a week for 13 or 19 weeks after initiation of DMBA (5-10 micrograms) or NF (50-1500 micrograms). DMBA administration (positive control) resulted in the formation of many papillomas, which were seen from week 8-9 after initiation. The negative controls administered acetone only were free of tumours. NF administration did not result in papilloma formation, even at high initiating doses of NF combined with a dose of TPA causing a systemic toxic effect in terms of a significant reduced body weight. The mechanism behind the absence of papilloma formation after administration of genotoxic and carcinogenic NF remains to be investigated. PMID- 8353861 TI - Natriuretic peptide system in human heart failure. AB - BACKGROUND: Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are a family of structurally related peptides that participate in the integrated control of renal and cardiovascular function. Previous studies suggest a functional role for these hormonal peptides in cardiorenal regulation in congestive heart failure (CHF). METHODS AND RESULTS: The present studies were performed in normal subjects (n = 6) and in patients with mild (New York Heart Association [NYHA] class I to II, n = 20) and severe (NYHA class III to IV, n = 20) CHF by use of radioimmunoassay and immunohistochemical staining (IHCS). Plasma ANP was significantly increased in both mild and severe CHF compared with normal subjects. In contrast, plasma BNP was only moderately increased in the severe CHF group, and plasma CNP concentration was unchanged in CHF compared with normal subjects. Atrial tissue concentrations of the natriuretic peptides did not parallel circulating concentrations. ANP predominated in normal atrial tissue, but BNP predominated in CHF. In ventricular tissue, IHCS staining was present for all three peptides in normal ventricular myocardium and was markedly enhanced in CHF. CONCLUSIONS: These studies support a differential regulation of ANP, BNP, and CNP circulating concentrations and tissue activity in human CHF. PMID- 8353862 TI - Right ventricular-vascular interaction in congestive heart failure. Importance of low-frequency impedance. AB - BACKGROUND: Vasodilator agents are widely used in congestive heart failure. These agents may have important effects on the pulsatile aspects of right ventricular hydraulic load. METHODS AND RESULTS: Fifteen patients with severe congestive heart failure were studied during cardiac catheterization by use of high-fidelity pressure transducers and a catheter-mounted flow velocity probe. Three graded doses of nitroprusside were infused as pulmonary artery (PA) pressure and flow were continuously recorded. From Fourier transforms of signal-averaged waves, PA impedance, hydraulic power, and wave reflection indices were derived. At the highest dose of nitroprusside (66 +/- 41 micrograms/min), cardiac output was significantly improved, whereas PA mean and wedge pressure, resistance, impedance at the first harmonic, characteristic impedance, and wave reflection amplitude were all reduced. At the dose (32 +/- 20 micrograms/min) at which cardiac output first showed improvement, only PA mean pressure and first-harmonic impedance were significantly reduced. Hydraulic power cost per unit of forward flow was also lowered at this dose, despite lack of significant change in pulmonary vascular resistance. At the lowest dose of nitroprusside (11 +/- 4 micrograms/min), six patients experienced a decrease in stroke volume, whereas the other nine were either unchanged (n = 1) or showed an increase (n = 8). Multiple regression revealed that only the change in first-harmonic impedance correlated with this effect, increasing when stroke volume decreased and decreasing when stroke volume increased (P = .02). The change in first-harmonic impedance at this dose appeared to be caused by alterations in the amplitude of PA wave reflections. At higher doses, changes in mean PA pressure (but not in pulmonary vascular resistance) correlated with changes in stroke volume. CONCLUSIONS: Nitroprusside vasodilation at low doses alters PA hemodynamics in congestive heart failure primarily through changes in low-frequency impedance. In some patients, this effect is associated with decreased stroke output. At higher doses, favorable alterations in resistance, low- and high-frequency impedance, and wave reflections all contribute to increased forward flow and decreased power requirement per unit forward flow. These findings show that ventricular-vascular interaction is importantly affected by pulmonary vasodilation and that appreciation of pulsatile properties is required to understand the effects of pulmonary vasodilation on cardiac output. PMID- 8353863 TI - Circulating beta-atrial natriuretic factor in congestive heart failure in humans. AB - BACKGROUND: beta-Atrial natriuretic factor (beta-ANF) is an antiparallel dimer of alpha-ANF (alpha-ANF) with diminished cyclic GMP generation in vitro. To date, the presence of beta-ANF in the circulation of humans with severe congestive heart failure (CHF) remains controversial. The current study was designed to determine the presence and magnitude of circulating beta-ANF in severe CHF, to correlate plasma beta-ANF with the degree of ventricular dysfunction, and to investigate the role of human plasma and atrial tissue in the degradation of beta ANF. METHODS AND RESULTS: Venous plasma samples were obtained from patients (n = 12) with severe CHF and normal volunteers (n = 8). Total plasma ANF was measured by radioimmunoassay. alpha-ANF and beta-ANF in nonextracted plasma were separated by gel filtration chromatography using a P-6 column. Right atrial tissue samples (n = 5) were collected from a different group of patients at the time of open heart surgery. 125I beta-ANF and I125 ANF were incubated with atrial tissue or plasma. The corresponding peak areas of beta-ANF were determined by Tamaya Digital Planimeter. beta-ANF represented 61% of total plasma ANF in CHF patients and was not detected in normal human plasma. The elevation of beta-ANF correlated with the severity of ventricular dysfunction. Thirty percent of beta-ANF and 100% alpha-ANF were converted to smaller peptide fragments in atrial tissue no conversion in plasma. CONCLUSIONS: beta-ANF is the principal form of circulating ANF in patients with severe CHF and correlates with the degree of left ventricular dysfunction. beta-ANF is not generated from alpha-ANF and may be degraded rapidly in atrial tissue to smaller peptide fragments that do not occur in plasma. As beta-ANF is reported to have reduced biological action, the current studies may support the conclusion that the ANF system in CHF has reduced functional activity despite increases in circulation concentrations. PMID- 8353864 TI - Unfavorable outcome in patients with primary electrical disease who survived an episode of ventricular fibrillation. AB - BACKGROUND: Prognosis in patients with ventricular tachyarrhythmia without structural heart disease (primary electrical disease) has been described as excellent. However, prognosis may be less favourable in the subgroup surviving an episode of ventricular fibrillation. METHODS AND RESULTS: We prospectively followed 19 consecutive patients (age, 13 to 66 years; mean age, 33 years) who had survived an episode of documented ventricular fibrillation. Structural heart disease, preexcitation, and long QT syndromes were excluded by thorough cardiologic evaluation. All patients underwent 24-hour Holter monitoring, exercise testing, and programmed electrical stimulation according to a standardized protocol. Holter monitoring revealed episodes of ventricular tachyarrhythmia in 5 patients. Exercise testing reproducibly provoked ventricular tachycardia in 2 patients. Baseline programmed electrical stimulation yielded inducibility of rapid ventricular tachyarrhythmia in 10 patients (53%) and noninducibility in 9 (47%). Nine patients were discharged on antiarrhythmic drug therapy. A defibrillator was implanted in 10 patients. During 43-month follow-up (range, 5 to 85 months; median, 41 months), major arrhythmic events recurred in 7 patients (37%). Four of these patients had noninducibility at baseline programmed electrical stimulation. Two patients on antiarrhythmic drugs had recurrent cardiac arrest: one died suddenly and the other was successfully resuscitated from ventricular fibrillation and subsequently underwent defibrillator implantation. In the other 5 patients, termination of (pre)syncopal episodes was associated with defibrillator shocks. Termination of ventricular fibrillation was documented by Holter recording in one of these patients. Specific markers predictive of a recurrent event could not be identified, although 6 of 7 patients with recurrent events had experienced at least one episode of cardiac arrest or (pre)syncope before the index episode. CONCLUSIONS: Patients with primary electrical disease presenting with ventricular fibrillation are at high risk of recurrence of major arrhythmic events during long-term follow-up. Noninducibility at baseline study does not predict an uneventful course. Also, early defibrillator implantation should be considered in these patients. PMID- 8353865 TI - Comparative mechanisms of antiarrhythmic drug action in experimental atrial fibrillation. Importance of use-dependent effects on refractoriness. AB - BACKGROUND: Antiarrhythmic drugs are considered to terminate atrial fibrillation by prolonging refractoriness, but direct experimental evaluation of this concept has been limited. The atria are activated rapidly during atrial fibrillation, and antiarrhythmic drugs are known to have important rate-dependent actions. The potential role of such properties in determining drug effects during atrial fibrillation has not been evaluated. METHODS AND RESULTS: We evaluated the effects of representative class Ia (procainamide), Ic (propafenone), and III (sotalol) antiarrhythmic drugs on sustained cholinergic atrial fibrillation and atrial electrophysiological properties in anesthetized, open-chest dogs. Loading and maintenance doses were used to produce stable plasma concentrations, and computer-based 112-electrode epicardial mapping was used to study atrial conduction and activation during atrial fibrillation. Clinically used doses of procainamide and propafenone terminated atrial fibrillation in 13 of 13 (100%) and 7 of 10 (70%) dogs, respectively, but a dose of sotalol (2 mg/kg IV) in the clinical range terminated atrial fibrillation in only 2 of 8 (25%) dogs (P = .0005 vs procainamide, P = .08 vs propafenone). Procainamide and propafenone prevented atrial fibrillation induction in 13 of 13 (100%) and 7 of 10 (70%) dogs, respectively, compared with none of 8 dogs for 2 mg/kg sotalol (P < .0001 vs procainamide, P = .004 vs propafenone). A larger dose of sotalol (cumulative dose, 8 mg/kg) was uniformly effective in terminating atrial fibrillation and preventing its induction. All drugs significantly increased atrial refractory period, with effects that were use dependent for propafenone but reverse use dependent for sotalol. Effective doses of all drugs significantly increased the wavelength for reentry at rapid atrial rates in the presence of vagal stimulation into the range observed under drug-free conditions in the absence of vagal input. The inefficacy of clinical doses of sotalol was explained by the reverse use dependence of its effects on refractoriness, which resulted in reduced effects on wavelength at rapid rates. The effects of propafenone on refractoriness were significantly increased at rapid rates, contributing to its ability to increase wavelength and terminate atrial fibrillation. Activation mapping showed that drugs terminated atrial fibrillation by reducing the number and increasing the size of reentry circuits, leading to termination by mechanisms related to block in the remaining circuit(s). CONCLUSIONS: We conclude that antiarrhythmic drugs terminate experimental atrial fibrillation by increasing the wavelength for reentry at rapid rates, leading to a reduction in the number of functional reentry circuits and, eventually, failure of reentrant excitation. Use-dependent effects on refractoriness can limit (in the case of the reverse use dependence of sotalol) or contribute (in the case of propafenone) to antiarrhythmic drug efficacy against atrial fibrillation by determining drug-induced changes in wavelength at rapid atrial rates. PMID- 8353866 TI - Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities. AB - BACKGROUND: The goal of the report was to study the long-term incidence and the independent predictors for chronic atrial fibrillation and stroke in 507 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis. METHODS AND RESULTS: From 1980 to 1989, we implanted 376 dual-chamber, 19 atrial, and 112 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 134 months (mean: 59 +/- 38 months for chronic atrial fibrillation, 65 +/- 37 months for stroke), actuarial incidence of chronic atrial fibrillation was 7% at 1 year, 16% at 5 years, and 28% at 10 years. Independent predictors for this event, from Cox's proportional hazards model, were history of paroxysmal atrial fibrillation (P < .001; hazard ratio [HR] = 16.84), use of antiarrhythmic drugs before pacemaker implant (P < .001; HR = 2.25), ventricular pacing mode (P = .003; HR = 1.98), age (P = .005; HR = 1.03), and valvular heart disease (P = .008; HR = 2.05). For patients with preimplant history of paroxysmal atrial fibrillation, independent predictors were prolonged episodes of paroxysmal atrial fibrillation (P < .001; HR = 2.56), long history of paroxysmal atrial fibrillation (P = .004; HR = 2.05), ventricular pacing mode (P = .025; HR = 1.69), use of antiarrhythmic drugs before pacemaker implant (P = .024; HR = 1.71), and age (P = .04; HR = 1.02). Actuarial incidence of stroke was 3% at 1 year, 5% at 5 years, and 13% at 10 years. Independent predictors for stroke were history of cerebrovascular disease (P < .001; HR = 5.22), ventricular pacing mode (P = .008; HR = 2.61), and history of paroxysmal atrial fibrillation (P = .037; HR = 2.81). CONCLUSIONS: Development of chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables and secondarily by the pacing modality. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation but not in those without it. PMID- 8353867 TI - Electrocardiographic correlates of spontaneous termination of ventricular tachycardia in patients with coronary artery disease. AB - BACKGROUND: In vitro studies have reported that beat-to-beat variance in tachycardia cycle length and in conduction and repolarization properties can result in spontaneous termination of reentrant arrhythmias. The purpose of this study was to define the ECG patterns associated with spontaneous termination of ventricular tachycardia in humans late after myocardial infarction. METHODS AND RESULTS: The QRS durations, QT intervals, and cycle lengths were measured on a beat-to-beat basis during episodes of sustained and spontaneously terminating ventricular tachycardias (VT) induced at antiarrhythmic drug-free and drug assessment electrophysiological studies. Twenty-six patients were studied. Four categories of inducible ventricular tachycardia were studied: inducible sustained ventricular tachycardia in an antiarrhythmic drug-free state, spontaneously terminating ventricular tachycardia in an antiarrhythmic drug-free state, sustained ventricular tachycardia on antiarrhythmic therapy, and spontaneously terminating ventricular tachycardia on antiarrhythmic therapy. The ECG patterns that were statistically related to spontaneous termination of ventricular tachycardia included impingement of the QTP interval on the tachycardia cycle length (P < .001) both in the presence and absence of drugs, transient shortening of QRS just before termination, and paradoxical prolongation of QTP after abrupt shortening of ventricular tachycardia cycle length. In addition, greater beat-to beat variances in tachycardia cycle lengths, QT intervals, and QRS durations were statistically associated with spontaneously terminating ventricular tachycardia. These ECG patterns did not occur during sustained episodes of ventricular tachycardia during the antiarrhythmic drug-free state or during ineffective antiarrhythmic drug therapy. CONCLUSIONS: A dynamic interplay between QRS duration, QT interval, and cycle length of tachycardia and their variances are associated with spontaneous termination of ventricular tachycardia in humans late after infarction. This study of ECG changes associated with spontaneous termination of ventricular tachycardia provides insight into potential mechanisms of antiarrhythmic drug efficacy. PMID- 8353868 TI - Frequency-dependent electrophysiologic effects of amiodarone in humans. AB - BACKGROUND: In general, antiarrhythmic agents that prolong the action potential duration (APD) have attenuated effects on repolarization at short cycle lengths (reverse frequency dependence), and this may limit their efficacy for controlling ventricular arrhythmias. The frequency-dependent effects of amiodarone on repolarization may differ from those of other antiarrhythmic agents and have not been determined in humans. METHODS AND RESULTS: The frequency-dependent effects of amiodarone on repolarization and conduction were determined during electrophysiologic study in 19 patients at drug-free baseline and after 11 days of amiodarone loading (1621 +/- 162 mg/d, group A) and in 15 additional patients after > or = 1 year of chronic amiodarone therapy (380 +/- 56 mg/d, group B). The two groups were similar in all clinical characteristics. The ventricular APD at 90% repolarization (APD90), right ventricular effective refractory period (VERP), and QRS duration were determined at paced cycle lengths of 300 to 600 milliseconds. In group A, amiodarone significantly (10% to 13%, P < .001) increased the APD90 at all paced cycle lengths by approximately 30 milliseconds compared with baseline. Similarly, there were no frequency-dependent effects on the percent increase in VERP. However, there was greater amiodarone-induced prolongation of the VERP magnitude at longer paced cycle lengths than at shorter cycle lengths (P = .04), although the VERP remained significantly prolonged at the shortest paced cycle length (300 milliseconds) by 33 +/- 22 milliseconds (16.9% increase from baseline, P < .001). Amiodarone significantly (P < .01) increased the QRS duration at paced cycle lengths < or = 500 milliseconds by a maximum of 28% compared with baseline measurements. The increase in ventricular conduction time was frequency dependent (P < .01), consistent with significant sodium channel blockade. The VERP/APD90 ratio (determined at twice diastolic threshold) was significantly prolonged by amiodarone (as compared with baseline) at cycle lengths > or = 400 milliseconds, indicative of both time- and voltage dependent effects on refractoriness. The increase in induced sustained ventricular tachycardia cycle length in group A patients after amiodarone loading was significantly correlated with the increase in VERP (r = .68, P = .044) but not with increases in QRS duration or APD90. In addition, there were no significant differences in frequency-dependent effects of amiodarone between groups A and B. CONCLUSIONS: The frequency-dependent response of the electrophysiologic effects of amiodarone are similar after 11 days of loading or > or = 1 year of chronic therapy. Amiodarone does not exert frequency-dependent effects on ventricular repolarization; it prolongs refractoriness by both time- and voltage-dependent mechanisms and exerts frequency-dependent effects on ventricular conduction. The absence of amiodarone-induced reverse frequency dependent effects on repolarization, together with its time-dependent effects on refractoriness may account in part for the high efficacy of the drug and its low propensity to cause torsade de pointes. PMID- 8353869 TI - Antiarrhythmic effects of selective prolongation of refractoriness. Electrophysiologic actions of sematilide HCl in humans. AB - BACKGROUND: Recent data have suggested that antiarrhythmic agents that act largely by delaying conduction may not be as effective in controlling ventricular arrhythmias as those that prolong repolarization. Recently, numerous "pure" class III agents have been developed. METHODS AND RESULTS: The antiarrhythmic and electrophysiologic profiles of sematilide, a "pure" class III agent, were determined in 27 patients with clinical ventricular arrhythmias and inducible sustained ventricular tachycardia during electrophysiologic study. After treatment with oral sematilide (mean dose, 133 +/- 29 mg every 8 hours), the patients underwent repeat 24-hour ambulatory ECG monitoring and electrophysiologic study. The baseline sinus cycle length and QT, QTc, JT, and JTc intervals were significantly increased 8 to 17% by sematilide (P = .001 to .029). There were no changes in the PR or QRS intervals. Sematilide (at a paced cycle length of 600 ms) significantly increased the atrial effective refractory period (238 +/- 32 to 264 +/- 32 ms; 11 +/- 16% increase from baseline; P = .013), atrioventricular nodal effective refractory period (296 +/- 74 to 354 +/- 71 ms; 20 +/- 19%; P = .029), and right ventricular effective refractory period (252 +/- 25 to 281 +/- 30 ms; 12 +/- 8%; P < .001) but did not significantly change the PA or HV intervals, the corrected sinus node recovery time, or the Wenckebach cycle length. Determination of the frequency-dependent effects of sematilide (n = 10) on the right ventricular monophasic action potential duration (APD90) during ventricular pacing at cycle lengths of 600 to 300 ms revealed that the APD90 was significantly prolonged by sematilide during ventricular pacing at 600 to 350 ms (APD90 increase of 40 +/- 17, 27 +/- 21, 18 +/- 18, and 14 +/- 15 ms, respectively) but not at 300 ms (APD increase of 13 +/- 19 ms). Sematilide significantly prolonged the APD90 to a greater degree at longer than at shorter cycle lengths (P = .02). The ventricular effective refractory period had a similar reverse frequency-dependent relation as the APD90. Sematilide had no effect on the ventricular effective refractory period-to-APD90 ratio or on ventricular conduction. Sematilide suppressed the induction of sustained ventricular tachycardia in 41% of all patients exposed to sematilide. Prolongation of ventricular refractoriness was correlated with ventricular tachycardia suppression. The right ventricular effective refractory period (at 600 ms) increased by 38 +/- 14 ms in patients whose sustained ventricular tachycardia was suppressed by sematilide and by 19 +/- 18 ms in patients not suppressed (P = .015). One patient developed short runs of pause-dependent nonsustained ventricular tachycardia. Eight patients were placed on long-term sematilide therapy, and during a mean follow-up period of 7.0 +/- 7.5 months, two patients developed sudden cardiac death, and one additional patient had recurrent sustained ventricular tachycardia. CONCLUSIONS: The electrophysiologic profile of sematilide is consistent with selective block of outward potassium currents and associated isolated lengthening of the ventricular effective refractory period and APD; sematilide demonstrates a significant degree of reverse frequency dependence of the ventricular APD and effective refractory period; and suppression of ventricular tachycardia inducibility by sematilide appears to be correlated with increases in the right ventricular effective refractory period. PMID- 8353870 TI - Influence of implantable cardioverter-defibrillators on the long-term prognosis of survivors of out-of-hospital cardiac arrest. AB - BACKGROUND: Survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction are at high risk for recurrent cardiac arrest and sudden cardiac death. The impact of the implantable cardioverter-defibrillator on long term prognosis in these patients is uncertain. METHODS AND RESULTS: Three hundred thirty-one survivors of out-of-hospital cardiac arrest (age, 56 +/- 13.7 years) underwent electrophysiologically guided therapy. Implantable defibrillators were placed in 150 patients (45.3%), and 181 patients (54.7%) received pharmacological and/or surgical therapy alone. Left ventricular ejection fraction was 35.2 +/- 16.6% in defibrillator recipients and 45.3 +/- 18.2% in nondefibrillator patients. Median patient follow-up was 24 months in the defibrillator group and 46 months in the nondefibrillator group. In a proportional hazards model, the independent predictors of total cardiac mortality were left ventricular ejection fraction of less than 0.40 (relative risk, 4.55; 95% confidence interval, 2.44 to 8.33; P = .0001), absence of an implantable defibrillator (relative risk, 2.70; confidence interval, 1.41 to 5.00; P = .017), and persistence of inducible sustained ventricular tachycardia (relative risk, 1.84; 95% confidence interval, 0.97 to 3.49; P = .045). The 1- and 5-year probabilities of survival free of cardiac mortality in patients with left ventricular ejection fraction of less than 0.40 were 94.3% and 69.6% with a defibrillator and 82.1% and 45.3% without a defibrillator, respectively. For patients with left ventricular ejection fraction of 0.40 or more, the 1- and 5-year probabilities of survival free of cardiac mortality were 97.7% and 94.6% with a defibrillator and 95.4% and 86.9% without a defibrillator, respectively. CONCLUSIONS: In survivors of out-of-hospital cardiac arrest, the implantable defibrillator is associated with a reduction in cardiac mortality, particularly in patients with impaired left ventricular function. PMID- 8353871 TI - Functional significance of intimal thickening as detected by intravascular ultrasound early and late after cardiac transplantation. AB - BACKGROUND: Detection of transplant coronary disease remains difficult. Both intravascular ultrasound (IVUS) imaging and functional coronary vasomotion studies have been used to evaluate this process. However, the time course of intimal thickening as assessed by IVUS and the relation between structure and function have not been explored. METHODS AND RESULTS: In 40 patients 1 to 8 years after transplantation, 108 coronary artery segments were analyzed by IVUS. Intimal index [% intimal area (lumen+intimal area)] and maximal thickness were used to quantify intimal thickening. Abnormal IVUS was present in 53 of 108 segments (49%) (mean intimal index of diseased segments, 23 +/- 2%; maximal thickness, 530 +/- 47 microns). For those patients with intimal thickening in all segments of the analyzed artery, more time had elapsed since transplantation (4.3 +/- 0.6 years) than for those whose arteries contained some normal (2.6 +/- 0.3 years) or all normal segments (2.2 +/- 0.6 years, P < .05). Both the proportion of segments with intimal thickening and the degree of thickening increased as a function of time after transplantation (P < .5). By multivariate analysis, the independent predictors of intimal thickening were increasing time after transplantation and pretransplantation hypercholesterolemia (P = .02). Within the cohort of 40 patients, endothelium-dependent vasomotor function was evaluated in 26 matched segments from 11 patients studied 1 year after transplantation and in 15 matched segments from 8 patients studied > or = 5 years after transplantation by serial infusions of acetylcholine (10(-8) to 10(-6) mol/L). Of the 26 segments assessed for structure/function correlation at 1 year after transplantation, 22 had no intimal thickening by IVUS. However, endothelial dysfunction was present in 13 of these normal segments (mean diameter constriction, 18.8 +/- 2.3%). Of the 15 segments studied > or = 5 years after transplantation, 11 had intimal thickening. Nine of these 11 segments had preserved endothelial function (mean diameter dilation, 8.6 +/- 2.9%). There was no relation between the degree of intimal thickening and the magnitude of the endothelium-dependent response to acetylcholine. CONCLUSIONS: This study has shown that intimal thickening after transplantation begins as a heterogeneous process and increases in extent and magnitude over time. Also, endothelial dysfunction occurs early before the intimal thickening; yet in those patients surviving > or = 5 years, endothelial function may recover even in the presence of moderate intimal pathology. The variable relation between intimal pathology and endothelial function is probably a result of the episodic nature of immune injury. PMID- 8353872 TI - Functional and neurochemical evidence for partial cardiac sympathetic reinnervation after cardiac transplantation in humans. AB - BACKGROUND: The presence of cardiac reinnervation in humans after cardiac transplantation has been widely debated, based on the application of differing methods for the assessment of neuronal function. Some of these techniques have been rather indirect; consequently, the time course and extent of cardiac reinnervation remains uncertain. METHODS AND RESULTS: To test for the presence of cardiac reinnervation after transplantation, we examined neurochemical (radiolabeled norepinephrine [NE] kinetics) and functional markers (power spectral analysis, heart rate response to exercise) of cardiac sympathetic nerve integrity in 15 cardiac transplantation recipients and 25 healthy control subjects of similar age. Cardiac transplantation subjects were studied 9 weeks to 8 years after cardiac transplantation (10 "early" patients < 18 months and 5 "late" patients > 2 years after cardiac transplantation). At rest, cardiac NE spillover was markedly attenuated early after transplantation (11.2 +/- 18.3 pmol/min) compared with subjects late after transplantation (105 +/- 11 pmol/min, P < .01) or in healthy control subjects (103 +/- 15 pmol/min, P < .01). Heart rate variability (measured by total spectral power) was significantly reduced in cardiac transplantation recipients compared with control subjects (59.4 +/- 30 vs 1673 +/- 516 milliseconds squared; P < .05), with evidence of a trend toward increasing spectral power late after transplantation. During exercise, the cardiac NE spillover was significantly lower in early cardiac transplantation recipients when compared with control subjects (163 +/- 50 vs 1876 +/- 418 pmol/min, P < .01). Late cardiac transplantation subjects showed a response intermediate (1080 +/- 254 pmol/min) between that of the early cardiac transplantation and control groups. However, measurements of the neuronal reuptake process for NE (assessed by the fractional extraction of plasma labeled NE across the heart and tritiated dihydroxyphenylglycol release) were significantly depressed in both early and late cardiac transplantation subjects. CONCLUSIONS: The present study demonstrates a partial restoration of cardiac sympathetic nerve function in humans up to 8 years after heart transplantation. PMID- 8353873 TI - Transcatheter occlusion of patent ductus arteriosus with adjustable buttoned device. Initial clinical experience. AB - BACKGROUND: Several devices are available for transcatheter occlusion of patent ductus arteriosus. Most of these devices either require complicated intracardiac maneuvering, have not been tried in humans, or need a large-sized sheath for implantation of the device. METHODS AND RESULTS: During a 26-month period ending November 1992, 14 patients underwent transcatheter closure of patent ductus arteriosus with an adjustable buttoned device delivered via a 7F sheath under an institutional review board-approved custom-made device protocol. The children were 15 months to 8 years of age with weight range of 7.2 to 19 kg. The patent ductus arteriosus measured from 2 to 7.5 mm (median, 3 mm) at the narrowest diameter and was conical, short, or tubular. They were occluded with devices measuring 15 to 20 mm. The ratio of pulmonary to systemic flow decreased (P < .01) from 1.9 +/- 0.6 (mean +/- SD; range, 1.3 to 3.2) to 1.05 +/- 0.1 (1 to 1.3). Continuous murmur of patent ductus arteriosus disappeared in all except 1 patient. Small residual shunts were detected by color Doppler studies in 4 of 14 patients (29%). All patients were followed for 1 to 24 months (mean, 6 +/- 7 months). The device was intact in all patients, and no breakage of the wires was noted. No shunts were seen in 12 of 14 patients (86%), and minute residual shunts were seen in 2 children. No major complications were encountered. CONCLUSIONS: It is concluded that transcatheter closure of patent ductus arteriosus with the adjustable buttoned device is feasible and effective and can be accomplished via small 7F sheaths; a 7F sheath is adequate for all ductal sizes; and the adjustable length of the loop accommodated all types of patent ductus arteriosus. Clinical trials on a larger number of patients are warranted. PMID- 8353874 TI - Left ventricular diastolic Doppler characteristics in beta-thalassemia major. AB - BACKGROUND: Diastolic left ventricular function expressed by diastolic Doppler characteristics of the left ventricle has never been properly investigated. METHODS AND RESULTS: Left ventricular inflow and pulmonary vein flow patterns were assessed by Doppler echocardiography in 88 beta-thalassemia major patients with normal left ventricular systolic function; 34 were young (age, 15.1 +/- 3.2 years) and 54 were adults (age, 25.1 +/- 3.6 years). The findings were compared with those obtained from 22 young (age, 13.8 +/- 2.4 years) and 24 adult (age, 25.3 +/- 4.1 years) normal individuals. In both groups of patients, peak flow velocities in early (E) and late (A) diastole were higher than in the control subjects (young E: P < .01; adult E: P < .001; young A: P < .05; adult A: P < .05), whereas no difference was found in the E/A ratio, deceleration time, or isovolumic relaxation time. Pulmonary vein systolic (S) and diastolic (D) velocities were also higher in beta-thalassemia major patients compared with the control subjects (young S: P < .05; adult S: P < .05; young D: P < .05; adult D: P < .05). Restrictive left ventricular abnormalities were only found in 7 patients who were among the oldest beta-thalassemia major population of the adult group (P < .01) with highly elevated mean serum ferritin. In comparison to the remaining adult patients, interventricular septum and left ventricular posterior wall thickness were increased (P < .01 and P < .01, respectively). The left atrium and right ventricle were dilated (P < .05 and P < .01, respectively). CONCLUSIONS: Doppler diastolic indexes in beta-thalassemia major patients with normal left ventricular systolic function are similar to those seen in conditions with an increased preload, probably because of chronic anemia. Only severe iron loading and deposition in the myocardium leads to the restrictive abnormalities of left ventricular filling. PMID- 8353875 TI - Diagnosis of intramural coronary artery in transposition of the great arteries using two-dimensional echocardiography. AB - BACKGROUND: An intramural coronary is an uncommon but potentially significant risk factor for transfer of the coronary arteries as part of the arterial switch operation for transposition of the great arteries. Preoperative diagnosis is advantageous because it helps prevent accidental injury to the intramural coronary artery during transection of the aortic root and excision of the coronary artery ostium from the aorta. Therefore, we investigated the reliability of two-dimensional echocardiography for detecting an intramural coronary artery in infants with d-transposition of the great arteries. METHODS AND RESULTS: All infants with d-transposition of the great arteries who underwent echocardiography and primary surgical repair at this institution between January 1987 and June 1992 were identified by search of the cardiology data base. From this group, all patients diagnosed with an intramural coronary artery were identified by review of the echocardiographic, surgical, and autopsy reports. Among 435 infants with transposition, 29 infants were diagnosed as having an intramural coronary artery. In 27 cases, the diagnosis was confirmed at surgery or autopsy, and there were two false-positive echocardiographic diagnoses (specificity, 99.5%). Twenty of the 27 patients with an intramural coronary artery were correctly diagnosed prospectively by echocardiography (sensitivity, 75%), including 17 of 23 patients with an intramural left coronary artery or left anterior descending coronary artery and 3 of 4 patients with an intramural right coronary artery. Two primary diagnostic criteria were identified: a major coronary artery arising from the contralateral septal sinus, near the usually intercoronary commissure, and a course for this vessel within the posterior aortic wall between the great arteries, creating a "double-border" appearance. Retrospective review using these criteria identified 26 of the 27 intramural arteries with no false-positive diagnoses. CONCLUSIONS: We conclude that coronary echocardiography is a very promising technique for detecting an intramural coronary artery in transposition of the great arteries. Careful prospective application of the identified diagnostic criteria should greatly improve the diagnostic accuracy. PMID- 8353876 TI - On-line assessment of left atrial area and function by echocardiographic automatic boundary detection. AB - BACKGROUND: Direct assessment of left atrial (LA) function has not been previously performed by noninvasive techniques; rather, LA function has been evaluated only indirectly via the analysis of transmitral flow velocity by Doppler. The recent development of real-time two-dimensional echocardiographic automatic boundary detection suggests that LA dimensions can be measured instantaneously to provide on-line assessment of its systolic and diastolic functions. METHODS AND RESULTS: We performed echocardiographic assessment of LA dimensions and function with automatic boundary detection in 45 patients by using the apical four-chamber view. Thirty-seven patients had structural or functional cardiac abnormalities, 35 patients were in sinus rhythm, and 10 patients had atrial fibrillation. Moderate to severe mitral regurgitation (MR) was noted in 16 patients. We also studied 10 control subjects to assess normal values of LA cavity area and indexes of function. From the instantaneously derived LA area, we derived indexes of systolic atrial expansion and diastolic atrial emptying. There were excellent correlations between the on-line-derived LA areas and those measured off line from videotaped images of conventional echocardiography (r = .91 for end-diastolic and .93 for end-systolic areas; SEE, 4.0 and 3.8 cm2, respectively). Patients in atrial fibrillation had depressed diastolic emptying index (0.17 +/- 0.05) compared with those in sinus rhythm (0.28 +/- 0.12; P < .02). Furthermore, patients with chronic MR exhibited larger LA cavity areas and depressed systolic and diastolic LA function as compared with those without MR. In addition, the Doppler-determined mitral E/A ratio was related to the ratio of early diastolic-to-late diastolic change in LA cavity area (r = .79; SEE 0.6; n = 35). CONCLUSIONS: Instantaneous LA cavity area measurement by echocardiographic automatic boundary detection is accurate and feasible in patients with diverse cardiac disorders. Patients with atrial fibrillation had a depressed diastolic emptying index and those with significant mitral regurgitation had depressed systolic expansion index as well. LA functional indexes in both systole and diastole can be derived providing an approach for quantitative evaluations of left atrial-left ventricular interactions based on geometric assessment noninvasively. PMID- 8353877 TI - Application of color Doppler flow mapping to calculate effective regurgitant orifice area. An in vitro study and initial clinical observations. AB - BACKGROUND: Analogous to stenotic valve area in the assessment of valvular stenosis, regurgitant orifice area (ROA) represents a fundamental parameter to assess valvular insufficiency. However, this parameter has not been routinely available up to now. In this study, we introduce the concept and provide the methodology to calculate regurgitant orifice area noninvasively, based on the analysis of the proximal flow convergence zone. METHODS AND RESULTS: In an in vitro study, we showed the feasibility and the accuracy of calculating effective ROA by the proximal flow convergence method throughout a range of driving pressures. The calculated and true ROA showed an excellent correlation with r = .992, delta ROA = -1.4 +/- 2.9 mm2. We then applied this concept clinically in 77 patients with mitral regurgitation and showed a very good correlation between effective ROA calculated by the proximal flow convergence method and calculated by the Doppler echocardiographic method: r = .95, delta ROA = -0.2 +/- 3.9 mm2. The ROA also correlated very well with Doppler echocardiographic-derived regurgitant stroke volume (r = .93) and regurgitant fraction (r = .82). In a subgroup of 20 patients who underwent invasive evaluation, the calculated effective ROA also correlated well with the angiographic grade of mitral regurgitation (rho = .81). CONCLUSIONS: We conclude that effective ROA represents unique information on the severity of a regurgitant lesion and can easily be calculated by the proximal flow convergence method. This new parameter should enhance our understanding and improve the serial assessment of valvular regurgitation. PMID- 8353878 TI - Validation of the proximal flow convergence method. Calculation of orifice area in patients with mitral stenosis. AB - BACKGROUND: It has been proposed recently that measuring the flow convergence region proximal to an orifice by Doppler flow mapping can provide a means of calculating regurgitant flow rate. Although verified in experimental models, this approach is difficult to validate clinically because there is no ideal gold standard for regurgitant flows in patients. However, this method also can be used to derive cardiac output or flow rate proximal to stenotic orifices and therefore to calculate their areas by the continuity equation (area = flow rate/velocity). Applying this method in mitral stenosis would provide a unique way of validating the underlying concept because the predicted areas could be compared with those measured directly by planimetry. METHODS AND RESULTS: We studied 40 patients with mitral stenosis using imaging and Doppler echocardiography. Doppler color flow recordings of mitral inflow were obtained from the apex, and the radius of the proximal flow convergence region was measured at its peak diastolic value from the orifice to the first color alias along the axis of flow. Flow rate was calculated assuming uniform radial flow convergence toward the orifice, modified by a factor that accounted for the inflow funnel angle formed by the mitral leaflets. Mitral valve area was then calculated as peak flow rate divided by peak velocity by continuous-wave Doppler. The calculated areas agreed well with those from three comparative techniques over a range of 0.5 to 2.2 cm2: 1) cross sectional area by planimetry (y = 1.08x-0.13, r = .91, SEE = 0.21 cm2); 2) area derived from the Doppler pressure half-time (y = 1.02x-0.14, r = .89, SEE = 0.24 cm2); and 3) area calculated by the Gorlin equation in the 26 patients who underwent catheterization (y = 0.89x + 0.08, r = .86, SEE = 0.24 cm2). Agreement with planimetry was similar for 22 patients with mitral regurgitation and 18 without it (P > .6), as well as for 6 in atrial fibrillation (P > .2). CONCLUSIONS: These results validate the proximal flow convergence concept in the clinical setting and also demonstrate that it can be extended to orifice area calculation using the continuity equation. PMID- 8353879 TI - Endothelin antiserum decreases volume-stimulated and basal plasma concentration of atrial natriuretic peptide. AB - BACKGROUND: Endothelin-1 (ET-1) is the most powerful factor known to release atrial natriuretic peptide (ANP) in vivo and in cultured cardiac myocytes or preparations of atrium. We tested the role of endogenous ET-1 in the regulation of ANP release by passive immunization in anesthetized rats. METHODS AND RESULTS: Intravenous injection of antiserum against ET-1 was shown to decrease basal and volume-stimulated plasma concentrations of ANP, whereas control serum was without effect. Antiserum generated in rabbits cross-reacted 100% with endothelin-2 and 3. In pentobarbital-anesthetized Wistar rats treated with ET-1 antiserum, plasma ANP concentration measured by radioimmunoassay was reduced by 37% from starting level after 10 minutes and by 30% after 60 minutes. Control rat serum had no effect on plasma ANP. Rapid intravenous infusion of 8 mL of 0.9% NaCl caused a sixfold increase of plasma ANP concentration in control rats but only twofold in rats pretreated with ET-1 antiserum (P < .01). This effect of ET-1 antiserum was dose dependent. ET-1 antiserum changed neither blood pressure nor heart rate significantly in anesthetized rats. Pretreatment with ET-1 antiserum did not affect the initial hypotensive response to intravenous ET-1 0.5 nmol/kg but significantly attenuated the subsequent hypertensive response to endothelin. CONCLUSIONS: Endothelin may be a physiological modulator of both basal and stimulated ANP release. PMID- 8353880 TI - Downregulation of c-myc expression by antisense oligonucleotides inhibits proliferation of human smooth muscle cells. AB - BACKGROUND: Proliferation of smooth muscle cells (SMCs) plays an important role in vascular pathobiology, being involved in the development of coronary restenosis and atherosclerosis. The activation of nuclear proto-oncogenes appears to be a final common pathway onto which various mitogenic signals coverage. Accordingly, we attempted to determine whether the activation of the c-myc nuclear proto-oncogene is essential for human SMC proliferation and explored the possibility of inhibiting their growth using antisense oligonucleotides directed against c-myc messenger RNA (mRNA). METHODS AND RESULTS: Proliferation of human SMCs was associated with an increase in c-myc mRNA expression after growth stimulation. Using 15-mer phosphorothioate oligonucleotides (oligomers), we tested their growth-inhibitory effect in SMCs in vitro. Antisense oligomers directed against the translation initiation region of the human c-myc gene exhibited a significant antiproliferative effect, whereas sense and mismatched oligomers did not inhibit the growth. The growth-inhibitory effect of c-myc antisense oligomers was dose dependent and preventable by an excess of sense oligomers. Furthermore, growth inhibition of SMCs treated with c-myc antisense oligomers was associated with a marked decrease in the c-myc mRNA level. Phosphorothioate oligomers remained stable in medium containing 20% serum and were detectable in SMCs as early as 1 hour after cell exposure. Intact oligomers rapidly accumulated intracellularly and persisted within human SMCs for at least 16 hours. CONCLUSIONS: c-myc antisense oligomers reduced c-myc expression and produced a significant growth inhibition of human SMCs, indicating an important role of c-myc gene activation in the process of SMC proliferation. Furthermore, extracellular stability and rapid cellular uptake provide the basis for future studies assessing the therapeutic role of the c-myc antisense approach in reducing SMC proliferation in the process of vascular restenosis. PMID- 8353881 TI - Both increased and decreased platelet adhesion to thermally injured subendothelium is caused by denaturation of von Willebrand factor. AB - BACKGROUND: Thermal angioplasty methods heat the arterial wall. We related platelet adhesion to the temperature to which subendothelium and purified adhesive proteins had been exposed. METHODS AND RESULTS: Cultured subendothelium, purified von Willebrand factor, collagen types I and III, or fibronectin was applied to glass coverslips. Coverslips were mounted on a heating device that applied a temperature gradient from 30 to 100 degrees C. De-endothelialized umbilical arteries were heated by immersion in phosphate-buffered saline. After cooling to room temperature, the surfaces were perfused with blood at 37 degrees C (shear rate, 1600 sec-1). Compared with 37 degrees C, platelet adhesion to endothelial cell matrix was significantly reduced by 25%, 50% or 75% after heating to 69 +/- 1 degree C (mean +/- SEM, P < .05), 72 +/- 1 degree C, or 75 +/ 1 degree C, respectively. Platelet coverage to umbilical artery subendothelium was in the same way significantly reduced after heating to 71 +/- 1 degree C, or 77 +/- 1 degree C, respectively. In contrast to endothelial cell matrix, however, heating to about 55 degrees C increased platelet coverage from 30 +/- 5% to 54 +/ 6% (P < .05). Both platelet adhesion to von Willebrand factor and monoclonal antibody binding against the GpIb binding site of von Willebrand factor showed a comparable temperature dependence as platelet adhesion to subendothelium, provided the proper von Willebrand factor concentration was used. Platelet adhesion to heated collagen types I and III was increased and maximal at 57 +/- 2 degrees C and 62 +/- 2 degrees C, respectively. Preincubation of collagen III with proteins resulted in decreased platelet adhesion with increasing temperatures. Heating did not affect the reactivity of fibronectin. CONCLUSIONS: In vitro platelet adhesion to human subendothelium is reduced by more than 50% after heating it briefly to more than 74 degrees C. Temperatures in excess of 80 degrees C reduce platelet adhesion by at least 85%. Thermal denaturation of von Willebrand factor is responsible not only for the decreased thrombogenicity above 71 degrees C but also for the increased thrombogenicity near 55 degrees C, provided that the von Willebrand factor concentration is low. PMID- 8353882 TI - Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation. AB - BACKGROUND: Platelet activating factor (PAF) is a phospholipid released upon stimulation by a variety of cells and has been implicated in several pathophysiological events such as asthma and inflammatory diseases. However, although the ability to aggregate platelets in vitro was the first biological activity ascribed to PAF, its role in contributing to the in vivo formation of arterial thrombi has not been thoroughly clarified. METHODS AND RESULTS: Intravascular platelet aggregation was initiated in two different animal models of arterial stenosis and endothelial injury. An external constrictor was positioned around rabbit carotid arteries and canine coronary arteries. After placement of the constrictor, a typical pattern of flow developed in the stenotic vessels. This pattern of flow, characterized by progressive reductions of carotid or coronary blood flow followed by spontaneous or induced restorations of flow (cyclic flow variations, CFVs), is related to recurrent platelet aggregation at the site of the stenosis followed by dislodgment of the thrombus. After observing CFVs for 30 minutes, BN52021 (up to 1.2 mg/kg), a potent and selective PAF antagonist, was given intravenously to rabbits (n = 12) and dogs (n = 10). BN52021 completely inhibited CFVs in 10 of 12 rabbits, whereas it was relatively ineffective in abolishing CFVs in dogs (only 2 of 10 animals inhibited). This different effect of BN52021 was not explained by too small a dose of the drug to achieve a complete blockade of PAF receptors in dogs, since ex vivo platelet aggregation was completely inhibited in both rabbits and dogs in response to exogenous PAF at concentrations up to 10(-5) mol/L. In a second group of 10 dogs, the hypothesis that PAF may become an important mediator of CFVs in dogs only several hours after endothelial injury was tested. After 30 minutes of baseline CFVs, these animals received a bolus of BN52021 up to 1.2 mg/kg. After this treatment, CFVs were completely abolished in 2 of 10 animals. The remaining 8 dogs were followed for an additional 8-hour period, at the end of which a second bolus of BN52021 was given. At this time, BN52021 was effective, as CFVs were abolished in 6 of 8 animals. These effects of BN52021 at 8 hours were not the consequence of a cumulative dose of the compound, since ex vivo platelet aggregation in response to PAF returned to baseline values immediately before administering the second dose. To identify possible sources of PAF other than aggregating platelets at the site of arterial stenosis, dogs in a third group were killed after 30 minutes (n = 7) and after 8 hours (n = 8) of CFVs. Histological sections of the stenotic coronary artery showed a marked leukocyte infiltration in these arterial segments after 8 hours of CFVs, whereas sections from dogs killed after 30 minutes showed only moderate or no infiltration. CONCLUSIONS: These data demonstrate that PAF plays an important role as a mediator of platelet aggregation in vivo in rabbits and dogs. In the canine model, PAF appears to become more important after leukocyte infiltration of the arterial wall, as it may contribute to initiating enough platelet activation to lead to cyclic flow variations at sites of arterial stenosis and endothelial injury. Data from the present study suggest that PAF antagonists may be used as antiplatelet agents. PMID- 8353883 TI - Inhibition of experimental neointimal hyperplasia and thrombosis depends on the type of vascular injury and the site of drug administration. AB - BACKGROUND: Heparin inhibits vascular smooth muscle cell proliferation in tissue culture and limits neointimal hyperplasia after experimental arterial injury but has been ineffective in reducing clinical restenosis. We examined how this discrepancy might reflect suboptimal drug-tissue interactions and/or differences in the vascular response to injury. METHODS AND RESULTS: Intravenous infusion was compared with local administration of heparin to injured rabbit iliac arteries either from drug-impregnated polymeric controlled release matrices in the perivascular space or from drug-releasing endovascular stents. Occlusive thrombosis, seen in 42% of control stent-bearing arteries, and partial thrombosis were virtually eliminated by heparin delivery from any route. Intimal area 14 days after balloon withdrawal denudation alone was reduced to an equal extent by continuous systemic heparin or by perivascular heparin for the first 3 days. In contrast, endovascular stents produced more exuberant neointimal hyperplasia, the inhibition of which required continuous rather than only early heparin administration. Neither perivascular delivery limited to the first 3 days nor stent-based delivery reduced neointimal hyperplasia as effectively. CONCLUSIONS: The antiproliferative and antithrombotic effects of heparin differ markedly, depending on the type of arterial injury and the mode of drug administration. Different forms of injury may require different therapies, and complications of arterial intervention such as excessive neointimal hyperplasia and thrombosis may demand alternate therapeutic regimens. Duration, dose, and site of delivery rather than frank resistance to therapy may explain why experimentally effective antiproliferative and antithrombotic agents fail clinically. PMID- 8353884 TI - Influence of the status of the renin-angiotensin system on the effect of cilazapril on neointima formation after vascular injury in rats. AB - BACKGROUND: Angiotensin converting enzyme (ACE) inhibition has been shown to prevent neointima formation after vascular injury in rats. However, clinical results evaluating restenosis after angioplasty have been negative. The goal of the present study was to evaluate the influence of the renin-angiotensin system (RAS) status on the effect of ACE inhibition on neointima formation. METHODS AND RESULTS: Arterial injury was produced by ballooning the left carotid artery of rats, and neointima formation was evaluated by morphometry 2 weeks after ballooning. The effects of cilazapril were assessed in four experimental groups: normotensive rats, spontaneously hypertensive rats, hypertensive rats with a renal artery stenosis induced by clipping (two-kidney, one-clip rats), and hypertensive rats with uninephrectomy, high salt intake, and administration of deoxycorticosterone (DOCA). In parallel groups of rats, measurement of plasma renin activity was made in order to characterize (at least at the plasma level) the status of the RAS. As expected, renal artery stenosis markedly increased plasma renin activity, and DOCA decreased it to undetectable levels. Cilazapril had a marked preventive effect on neointima formation in normotensive rats, spontaneously hypertensive rats, and two-kidney, one-clip rats but was ineffective in DOCA rats. CONCLUSIONS: We conclude that the status of the RAS has a major influence on the effect of cilazapril on neointima formation after vascular injury. PMID- 8353885 TI - Tone-dependent coronary arterial-venous pressure differences at the cessation of venous outflow during long diastoles. AB - BACKGROUND: The origin and magnitude of the back pressure opposing diastolic coronary inflow remain controversial. The arterial pressure at which coronary inflow stops during a prolonged diastole, ie, "zero-flow pressure," is higher than coronary venous pressure. However, because of capacitive discharge as distending pressure falls, flow at the microcirculatory level exceeds inflow, and coronary outflow ceases later than inflow. If coronary arterial pressure continues to exceed venous pressure at the point of venous flow cessation, zero flow pressure cannot be an artifact of capacitive discharge. METHODS AND RESULTS: Coronary inflow and outflow, arterial pressure, and right atrial pressure have been measured during long diastoles in closed-chest dogs chronically instrumented with volumetric flow probes on the great cardiac vein or coronary sinus as well as the circumflex artery. Although venous outflow continued for 1 to 4 seconds after arterial inflow ceased, coronary artery pressure at the point of venous flow cessation (Pfv = 0) always exceeded right atrial pressure (13 +/- 1.3 mm Hg [SEM] vs 6 +/- 0.7 mm Hg, P < .001). When vasomotor tone was augmented using vasopressin, the diastolic pressure-flow relation shifted to the right, with Pfv = 0 increasing to 21 +/- 2.4 mm Hg despite an unchanged right atrial pressure (6 +/- 0.5 mm Hg). CONCLUSIONS: Transcoronary pressure differences persist when venous outflow stops and are larger when vasomotor tone is augmented. Measurements of zero-flow pressure that exceed venous pressure cannot be considered an artifact of continuing capacitive discharge after the cessation of arterial inflow. Diastolic coronary back pressure exceeds right atrial pressure and is tone dependent. PMID- 8353886 TI - Role of K+ATP channels in coronary vasodilation during exercise. AB - BACKGROUND: The mechanism of metabolic regulation of coronary vascular tone is still unclear. Therefore, we examined the role of vascular smooth muscle K+ATP channels in regulating coronary blood flow under resting conditions, during increments in myocardial metabolic demand produced by treadmill exercise, and in response to a brief ischemic stimulus. METHODS AND RESULTS: Ten chronically instrumented dogs were studied at rest and during a four-stage exercise protocol under control conditions and during intracoronary infusion of the K+ATP channel blocker glibenclamide at rates of 10 and 50 micrograms.kg-1 x min-1. Glibenclamide (50 micrograms.kg-1 x min-1) decreased coronary blood flow at rest from 51 +/- 4 to 42 +/- 6 mL/min (P < .05), decreased myocardial oxygen consumption from 5.70 +/- 0.31 to 4.11 +/- 0.56 mL O2/min (P < .05), and decreased systolic wall thickening from 21 +/- 3% to 12 +/- 3% (P < .05). The depression of systolic wall thickening produced by glibenclamide was reversed when coronary blood flow was restored to the control level with intracoronary nitroprusside, indicating a primary effect of glibenclamide on coronary flow during resting conditions. However, glibenclamide did not impair the increases of coronary blood flow, myocardial oxygen consumption, and systolic wall thickening that occurred during exercise. In eight resting awake dogs, 50 micrograms.kg-1 x min-1 glibenclamide decreased the peak reactive hyperemia blood flow rate following a 20-second coronary occlusion from 149 +/- 14 mL/min during control conditions to 111 +/- 15 mL/min (P < .05), decreased the duration of reactive hyperemia from 49 +/- 6 to 33 +/- 3 seconds (P < .05), and decreased reactive hyperemia excess flow from 33 +/- 5 to 20 +/- 4 mL (P < .05). CONCLUSIONS: These data demonstrate that K+ATP channels modulate coronary vasomotor tone under resting conditions and contribute to coronary vasodilation during ischemia. However, the coronary vasculature retains the capacity to dilate in response to increases in oxygen demand produced by exercise when K+ATP channels are blocked. PMID- 8353887 TI - Effects of active compression-decompression resuscitation on myocardial and cerebral blood flow in pigs. AB - BACKGROUND: This study was designed to assess the effects of a modified cardiopulmonary resuscitation (CPR) technique that consists of both active compression and active decompression of the chest (ACD CPR) versus standard CPR (STD CPR) on myocardial and cerebral blood flow during ventricular fibrillation both before and after epinephrine administration. METHODS AND RESULTS: During a 30-second period of ventricular fibrillation cardiac arrest, 14 pigs were randomized to receive either STD CPR (n = 7) or ACD CPR (n = 7). Both STD and ACD CPR were performed using an automated pneumatic piston device applied midsternum, designed to provide either active chest compression (1.5 to 2.0 in.) and decompression or only active compression of the chest at 80 compressions per minute and 50% duty cycle. Using radiolabeled microspheres, median total myocardial blood flow after 5 minutes of ventricular fibrillation was 14 (7 to 30, minimum to maximum) STD CPR versus 30 (9 to 46) mL.min-1 x 100 g-1 with ACD CPR (P < .05). Median cerebral blood flow was 15 (10 to 26) mL.min-1 x 100 g-1 with STD CPR and 30 (21 to 39) with ACD CPR (P < .01). When comparing STD with ACD CPR, aortic systolic (62 mm Hg [48 to 70] vs 80 [59 to 86]) and diastolic (22 [18 to 28] vs 28 [21 to 36]) pressures, calculated coronary systolic (30 [22 to 36] vs 49 [37 to 56]) and diastolic (18 [16 to 23] vs 26 [21 to 31]) perfusion pressures, end-tidal CO2 (1.4% [0.8 to 1.8] vs 2.1 (1.8 to 2.4]), cerebral O2 delivery (3.1 mL.min-1 x 100 g-1 [1.5 to 4.5] vs 5.3 [3.8 to 7.5]), and cerebral perfusion pressure (14 mm Hg [4 to 22] vs 26 [6 to 34]) were all significantly higher with ACD CPR: To compare these parameters before and after vasopressor therapy, a bolus of high-dose epinephrine (0.2 mg/kg) was given to all animals after 5 minutes of ventricular fibrillation. Organ blood flow and calculated perfusion pressures increased significantly in both the STD and ACD groups after epinephrine. The differences observed between STD and ACD CPR before epinephrine were diminished 90 seconds after epinephrine but were again statistically significant when assessed 5 minutes later, once the acute effects of epinephrine had decreased. No difference in short-term resuscitation success was found between the two groups. CONCLUSIONS: We conclude that ACD CPR significantly increases myocardial and cerebral blood flow during cardiac arrest in the absence of vasopressor therapy compared with STD CPR: PMID- 8353888 TI - Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. AB - BACKGROUND: To test the hypothesis that the heat shock response is associated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress. METHODS AND RESULTS: Rabbits were divided into four groups. Ischemic pretreatment (n = 15) comprised four 5 minute episodes of coronary ligation separated by 10 minutes of reperfusion. The corresponding control group (n = 21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n = 16) involved whole-body temperature elevation to 42 degrees C for 15 minutes; corresponding controls (n = 15) were treated with anesthetic alone. Twenty-four hours later, hearts were removed for HSP estimation or infarct size assessment after a 30-minute coronary ligation. Myocardial HSP72 content assessed by Western blotting was elevated by both ischemic and thermal pretreatments (2.5 +/- 0.2 units, n = 4, and 2.8 +/- 0.3 units, n = 4, mean +/- SEM; P = NS, respectively) compared with the corresponding control groups (1.0 +/- 0.3, n = 4, P < or = .01 and 0.3 +/- 0.1, n = 4, P < or = .01, respectively). HSP60 was preferentially elevated by ischemic pretreatment. After a 30-minute coronary occlusion and 120 minutes of reperfusion, ischemic and thermal pretreatments limited infarct size as a percentage of the volume at risk by 28.8 +/- 5.2% vs 52.0 +/- 5.2%, P < or = .01 and 32.8 +/- 3.8% vs 56.9 +/- 6.5%, P < or = .01, respectively. CONCLUSIONS: Myocardial stress protein induced by either sublethal thermal or ischemic injury is associated with myocardial salvage. Our findings suggest that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our observations may have important implications regarding myocardial adaptation to brief periods of ischemia. PMID- 8353889 TI - Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction. AB - BACKGROUND: The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size. METHODS AND RESULTS: Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P < .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P < .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P < .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was < 1% of normal myocardial blood flow. CONCLUSIONS: We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart. PMID- 8353890 TI - Regional differences in function within noninfarcted myocardium during left ventricular remodeling. AB - BACKGROUND: The mechanisms of ventricular enlargement and dysfunction during postinfarct remodeling remain largely unknown. Although global left ventricular architectural changes after myocardial infarction are well documented, differences in function between adjacent and remote noninfarcted myocardium during left ventricular remodeling have not been investigated. These functional differences may relate to regional differences in wall stress during contraction and may contribute to chamber enlargement and global dysfunction after infarction. METHODS AND RESULTS: Anteroapical infarcts were produced in seven sheep by ligation of the mid left anterior descending coronary artery and second diagonal branch at thoracotomy. Magnetic resonance short-axis and long-axis images tagged by spatial modulation of magnetization were obtained before and 1 week, 8 weeks, and 6 months after infarction. Left ventricular volumes, mass, ejection fraction, and lengths of infarcted and noninfarcted segments were measured. Circumferential and longitudinal shortening in the subendocardium and subepicardium, wall thickness, and histopathology were assessed in infarcted segments and regions adjacent to and remote from the infarct border. We found that a difference in circumferential and longitudinal segmental shortening between adjacent and remote noninfarcted myocardium present at 1 week persisted up to 6 months after myocardial infarction. However, partial improvement of function in adjacent regions occurred during infarct healing between 1 and 8 weeks after infarction. Left ventricular volume increased up to 6 months after infarction, out of proportion to the concomitant eccentric hypertrophy, whereas the ejection fraction fell. Left ventricular dilatation late in the remodeling process was secondary to lengthening of noninfarcted segments, which were free of significant fibrosis. CONCLUSIONS: Left ventricular dilatation and eccentric hypertrophy during remodeling are associated with persistent differences in segmental function between adjacent and remote noninfarcted regions. These functional differences may reflect increased wall stress in adjacent noninfarcted regions and contribute to the global dilatation and dysfunction characteristic of left ventricular remodeling after infarction. PMID- 8353891 TI - Combination treatment with captopril and the thyroid hormone analogue 3,5 diiodothyropropionic acid. A new approach to improving left ventricular performance in heart failure. AB - BACKGROUND: An agent that improves left ventricular (LV) performance by non-cAMP mediated mechanisms would be valuable in the treatment of chronic heart failure. We have shown earlier that the thyroid hormone analogue 3,5-diiodothyropropionic acid (DITPA) binds to nuclear receptors, alters transcription of T3-responsive genes, and increases +dP/dtmax in hypothyroid rats with substantially less effect on heart rate and metabolism than thyroid hormone, which makes it a selective cardiotonic agent. METHODS AND RESULTS: To determine whether DITPA might be useful in treating heart failure, we compared chronic treatment with normal saline, captopril (2 g/L), or the combination of DITPA (375 micrograms/100 g) and captopril (2 g/L) in Sprague-Dawley rats beginning 3 weeks after coronary artery ligation. Both DITPA/captopril and captopril treatment decreased LV end-diastolic pressure compared with controls (21 +/- 2 and 26 +/- 2 mm Hg, respectively, vs 34 +/- 3 mm Hg, P < .05 for each). The addition of DITPA to captopril produced a 36% increase in resting cardiac index (P < .05) and shifted the cardiac function curve upward and to the left, indicative of enhanced myocardial performance. Also, DITPA/captopril compared with captopril treatment or control produced an increase in the rate of LV relaxation, as manifested by a decrease in tau, the time constant of LV pressure decline (17.5 +/- 1.0 vs 22.2 +/- 1.7 milliseconds, P < .05) and a larger absolute value for -dP/dtmax (-4561 +/- 361 vs -3346 +/- 232 mm Hg/s, P < .05). These changes occurred without changes in heart rate, LV mass, LV systolic pressure, or peripheral resistance relative to captopril treatment (P > .05). CONCLUSIONS: The combination of DITPA and captopril improved cardiac output, increased -dP/dtmax, and increased the rate of LV relaxation to a greater extent than captopril treatment in the rat postinfarction model of heart failure. Use of a cardiotonic analogue of thyroid hormone represents a new approach to improving LV performance and may be a useful adjunct to afterload reduction for the treatment of heart failure. PMID- 8353892 TI - Defining coronary restenosis. Newer clinical and angiographic paradigms. PMID- 8353893 TI - Disordered eicosanoid formation in pregnancy-induced hypertension. PMID- 8353894 TI - Congestive heart failure in a 70-year-old man. PMID- 8353895 TI - Impact of implantable cardioverter-defibrillators on prognosis of cardiac arrest survivors. A continuing controversy. PMID- 8353896 TI - Do antisense approaches to the problem of restenosis make sense? PMID- 8353897 TI - Ischemic preconditioning and adenosine release. PMID- 8353898 TI - Progressive left ventricular dysfunction and remodeling after myocardial infarction. PMID- 8353899 TI - Is implantable defibrillator therapy the therapy of choice for all patients with malignant ventricular tachyarrhythmias? PMID- 8353900 TI - Coronary spasm and the development of coronary atherosclerosis. PMID- 8353901 TI - Coronary atherosclerosis on angiography--progress or regress, and why? PMID- 8353903 TI - Behavior change and compliance: keys to improving cardiovascular health. How health behavior relates to risk factors. PMID- 8353902 TI - Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction? AB - Thrombolytic therapy significantly improves the natural history of acute myocardial infarction, but recent data suggest that current reperfusion strategies have yet to realize the maximum potential for reduction of mortality and salvage of ventricular function. Coronary patency rates as high as 85% assessed by angiography 90 minutes after initiation of treatment greatly overestimate the efficacy of thrombolytic regimens, as this conventional angiographic "snapshot" view does not satisfactorily reflect the dynamic processes of coronary artery recanalization and reocclusion or the adequacy of myocardial perfusion. In fact, only the unusual patient appears to achieve optimal reperfusion for acute myocardial infarction, with a substantial deterioration of benefit in many patients due to insufficiently early or rapid recanalization, incomplete patency with TIMI grade 2 flow or critical residual coronary stenoses, absence of myocardial tissue reflow despite epicardial artery patency, intermittent coronary patency, subsequent reocclusion, or reperfusion injury. Recently developed techniques to critically assess the quality of reperfusion, coupled with the introduction of novel pharmacological agents and an improved understanding of the roles and mechanisms of existing thrombolytic and adjunctive drugs, have provided the opportunity to overcome many of the present limitations of reperfusion therapy. Emerging strategies to achieve optimal reperfusion are directed at enhancement of the velocity and quality of thrombolysis, amelioration of the adverse effects of reperfusion, and use of alternative pathways to myocardial salvage. PMID- 8353904 TI - Setting the policy, education, and research agenda to reduce tobacco use. Workshop I. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health. PMID- 8353905 TI - Behavior changes and the prevention of high blood pressure. Workshop II. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health. PMID- 8353906 TI - Obesity. Workshop III. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health. AB - The workshop provided the opportunity to discuss issues and develop and integrate ideas. The following recommendations for public policies, education programs, and high-priority research initiatives were developed: Recommendations for Public Policies: Focus on prevention by requiring school programs to emphasize appropriate diet, physical activity, and general health guidance to promote cardiovascular health and prevent disease through federal funding. Provide better access to exercise (city planning, work-site interventions). Influence food availability and accessibility. Influence reimbursement policies for effective early intervention and prevention strategies for obesity. Reevaluate policies for use of drugs in the treatment of obesity. Recommendations for Education Programs: Sponsor scientific workshop to: Define the most appropriate weight standards for prevention and treatment. Identify who should lose weight and why, when, and how. Promote the fact that obesity is an important health risk factor, even at moderate levels, and that excess visceral fat is particularly hazardous. Target health care professionals, consumers, and the media for education about: Nature of obesity as a heterogeneous syndrome. Recommendations for diet, exercise, behavioral interventions, drugs, and surgery. Recognition of special needs of populations of different ethnicity, gender, age, etc. State-of-the-art treatment and treatment programs. High-Priority Research Initiatives: Build better bridges between basic research and treatment/prevention practices. Acknowledge that obesity is a heterogeneous syndrome that may best be characterized as different obesities. Research on defining subtypes. Implications for etiology and treatment. Better characterization of genotypes and phenotypes. Study the effects of weight loss, weight gain,and weight cycling on medical and psychosocial outcomes and mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353907 TI - Lipids. Workshop IV. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health. PMID- 8353908 TI - Physical inactivity. Workshop V. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health. PMID- 8353909 TI - Behavior change and compliance: keys to improving cardiovascular health. Workshop VI. AHA Prevention Conference III. PMID- 8353910 TI - AHA out front in fight to save animal research laboratories. PMID- 8353911 TI - The National Heart, Lung, and Blood Institute value function: measure for measure. PMID- 8353912 TI - Calcium antagonists differently inhibit proliferation of human coronary smooth muscle cells in response to pulsatile stretch and platelet-derived growth factor. AB - BACKGROUND: Vascular smooth muscle cell proliferation is the key event of coronary artery disease. Mechanical forces, in particular, pulsatile stretch and platelet-derived growth factor, may play an important role. METHODS AND RESULTS: Vascular smooth muscle cells were cultured from the media of human left descending coronary arteries obtained from organ donors using the explant method. To study effects of pulsatile stretch on vascular smooth muscle cell proliferation, a computer-controlled in vitro pulsatile stretch device was used. Cells were seeded onto Flex I culture plates with deformable membranes and exposed to pulsatile stretch (60 cycles per minute) and/or growth factors. Proliferation of smooth muscle cells was determined by 3H-thymidine incorporation. Pulsatile stretch markedly stimulated 3H-thymidine incorporation of coronary smooth muscle cells (180 +/- 15 to 432 +/- 27 cpm/10(5) cells; P < .05) after 24 hours and increased cell number after 6 days (10.3 +/- 0.7 x 10(4)/mL; P < .05). Platelet-derived growth factor-AB (0.01 to 10 ng/mL) concentration-dependently stimulated 3H-thymidine incorporation in coronary smooth muscle cells (EC50, 0.1 ng/mL) and had additive effects with pulsatile stretch. The Ca2+ antagonist verapamil (10(-7) to 10(-5) M) concentration dependently inhibited proliferation stimulated by platelet-derived growth factor back to control levels (P < .05 to .01) but not that induced by pulsatile stretch. CONCLUSIONS: Pulsatile stretch and platelet-derived growth factor are potent stimuli for proliferation of coronary smooth muscle cells. The selective inhibitory effect of a Ca2+ antagonist on smooth muscle cell proliferation stimulated by platelet-derived growth factor but not by pulsatile stretch may explain why the drugs have only modest antiatherogenic effects in patients with coronary artery disease. PMID- 8353913 TI - Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group. AB - BACKGROUND: Peripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD. METHODS AND RESULTS: The AAI was measured in 5084 participants > or = 65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI (< 0.8, > or = 0.8 to < 0.9, > or = 0.9 to < 1.0, > or = 1.0 to < 1.5). Analyses tested for a dose-response relation of the AAI with clinical CVD, risk factors, and subclinical disease. The cumulative frequency of a low AAI was 7.4% of participants < 0.8, 12.4% < 0.9, and 23.6% < 1.0. participants with an AAI < 0.8 were more than twice as likely as those with an AAI of 1.0 to 1.5 to have a history of myocardial infarction, angina, congestive heart failure, stroke, or transient ischemic attack (all P < .01). In participants free of clinical CVD at baseline, the AAI was inversely related to history of hypertension, history of diabetes, and smoking, as well as systolic blood pressure, serum creatinine, fasting glucose, fasting insulin, measures of pulmonary function, and fibrinogen level (all P < .01). Risk factor associations with the AAI were similar in men and women free of CVD except for serum total and low-density lipoprotein cholesterol, which were inversely associated with AAI level only in women. Risk factors associated with an AAI of < 1.0 in multivariate analysis included smoking (odds ratio [OR], 2.55), history of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (OR, 2.36). In the 3372 participants free of clinical CVD, other noninvasive measures of subclinical CVD, including carotid stenosis by duplex scanning, segmental wall motion abnormalities by echocardiogram, and major ECG abnormalities were inversely related to the AAI (all P < .01). CONCLUSIONS: There was an inverse dose-response relation of the AAI with CVD risk factors and subclinical and clinical CVD among older adults. The lower the AAI, the greater the increase in CVD risk; however, even those with modest, asymptomatic reductions in the AAI (0.8 to 1.0) appear to be at increased risk of CVD. PMID- 8353914 TI - Increased risk of coronary heart disease death in men with low total and low density lipoprotein cholesterol in the Russian Lipid Research Clinics Prevalence Follow-up Study. AB - BACKGROUND: A continuously increasing risk of coronary heart disease with increasing levels of cholesterol has been reported by many observational and experimental studies. However, this type of association has not been observed in studies in the Russian Lipid Research Clinics. METHODS AND RESULTS: Twelve-year coronary heart disease mortality among 40- to 59-year-old men was analyzed in the Moscow and St Petersburg examines in the Russian Lipid Research Clinics Program. The baseline survey examined 6431 men fasting and free of prevalent coronary heart disease. Lipids and lipoproteins, blood pressure, body mass, education level, alcohol intake, and smoking history were obtained. Mortality follow-up was based on contacts with participants or their relatives or neighbors. Coronary heart disease mortality was analyzed based on risk factor levels and was further divided into rapid and nonrapid deaths. A J-shaped cholesterol-coronary heart disease risk function was present for both total and low-density lipoprotein cholesterol. Further examination showed hypocholesterolemic men to have lower low density and higher high-density lipoprotein cholesterol, higher alcohol consumption, leaner body mass, and less education than men with normal or high cholesterol levels. When education level was considered, the J-shaped risk function was present only among men with less than a high school education. When deaths were classified into rapid (less than 24 hours after onset of symptoms) and nonrapid, the J-shaped risk function was restricted to rapid deaths. CONCLUSIONS: The results of disclose a sizeable subset of hypocholesterolemics in this population at increased risk of cardiac death associated with lifestyle characteristics. PMID- 8353915 TI - Regional blood flow, oxidative metabolism, and glucose utilization in patients with recent myocardial infarction. AB - BACKGROUND: Metabolic imaging with positron emission tomography (PET) can detect tissue viability in clinical infarct regions. With appropriate tracer kinetic models and serial PET imaging, regional myocardial blood flow and rates of metabolism can now be quantified in patients with recent myocardial infarctions. METHODS AND RESULTS: Serial PET imaging with [13N]ammonia, [11C]acetate, and 18F deoxyglucose was performed in 22 patients with recent infarctions to measure regional blood flow (in milliliters per gram per minute), glucose metabolism (in micromoles per gram per minute), and oxidative metabolism (in clearance rate per minute). Hypoperfused clinical infarct regions were classified as "PET mismatch" if 18F was increased relative to 13N activity or "PET match" if 13N and 18F activities were reduced concordantly. Blood flows differed significantly between normal, mismatch, and match segments (0.83 +/- 0.20, 0.57 +/- 0.20, and 0.32 +/- 0.12 mL.g-1.min-1, respectively). The relation between oxidative metabolism and blood flow was piecewise linear and differed significantly between PET mismatch and PET match. Oxidative metabolism was less severely reduced than blood flow in mismatch regions but but reduced in proportion to blood flow in match regions. There was considerable overlap of blood flows between both types of PET segments. CONCLUSIONS: Quantification of regional blood flow and substrate metabolism in postinfarction patients revealed alterations in the relation between substrate delivery and consumption demonstrated previously only in invasive animal experiments. The preserved oxidative metabolism in myocardium with PET mismatches may be ascribed to a regional increase in oxygen extraction. Such increase together with preserved glucose utilization may be the prerequisite for survival of ischemically injured myocardium. PMID- 8353916 TI - Electrocardiographic diagnosis of postinfarction regional pericarditis. Ancillary observations regarding the effect of reperfusion on the rapidity and amplitude of T wave inversion after acute myocardial infarction. AB - BACKGROUND: The ECG recognition of diffuse pericarditis following acute myocardial infarction has been based on changes of the ST segment and, to a lesser extent, alterations of the PQ segment. No ECG criteria exist for the diagnosis of postinfarction regional pericarditis. Recently, it was observed that the T wave evolution follows an atypical pattern before fatal free wall rupture and that this pattern is due to the associated pericarditis. Therefore, this study was conducted on 200 patients with acute myocardial infarction to further elucidate the sensitivity and specificity of the atypical T wave changes in patients with regional postinfarction pericarditis without rupture and to assess the affect of lytic treatment on the rapidity and amplitude of postinfarction T wave evolution. METHODS AND RESULTS: An analysis of the clinical courses and serial ECGs of 200 consecutive patients with acute myocardial infarction was performed. Among 43 patients with postinfarction pericarditis, the pattern of T wave evolution consistently differed from the customary postinfarction pattern of T wave evolution. This unusual evolutionary course was expressed as either persistently positive T waves 48 or more hours after infarction (67%) or premature, gradual reversal of inverted T waves to positive deflections (33%). The sensitivity and specificity of these T wave alterations were 100% and 77%, respectively. The only other processes identified that caused this type of postinfarction T wave evolution were cardiopulmonary resuscitation, reinfarction, and very small infarcts. Both reperfusion, as judged by the creatine kinase-MB curve, and patency, as assessed by the angiogram, were correlated with the rapidity and depth of T wave inversion. Ninety percent of patients with reperfusion attained a maximum T wave negativity of 3 mm or more within 48 hours after the onset of chest pain in the lead that initially displayed the greatest ST segment elevation. Seventy-six percent of patients without reperfusion attained a maximum negativity of 2 mm or less within 72 hours. Thus, like the ST segment, accelerated evolution and deepening of the T wave may be noninvasive markers of reperfusion. CONCLUSIONS: First, premature reconcordancy of the ST segment and T wave after acute myocardial infarction is a sensitive, reasonably specific, and easily recognizable ECG manifestation of postinfarction regional pericarditis. Second, reperfusion is associated with accelerated evolution and deepening of the T waves following acute myocardial infarction. PMID- 8353917 TI - Late potentials and ventricular enlargement after myocardial infarction. A new role for high-resolution electrocardiography? AB - BACKGROUND: Arrhythmias are common in patients who have developed ventricular enlargement after myocardial infarction. METHODS AND RESULTS: A prospective study was undertaken to assess the relation between ventricular dilatation and the development of late potentials after myocardial infarction. Echocardiograms and signal-averaged ECGs were recorded on days 1,3,7, and 42 in 52 patients with a first anterior myocardial infarction. Twenty-nine percent of patients were late potential-positive on their initial signal-averaged ECG recorded on the day of admission. The incidence of late potentials rose during the next week to a peak of 42% at day 7, declining to 13% by day 42. The presence of late potentials on the day of admission was associated with an increase in end-diastolic volume index of 16.1 +/- 6.0 mL/m2 (mean +/- SEM), compared with a decreased of 4.7 +/- 2.7 mL/m2 among late potential-negative patients (P < .006). Qualitatively similar results were evident for late potentials on day 3 and day 7. By contrast, there was no association between late potentials on day 42 and ventricular dilatation. Marked dynamic changes in late potentials were evident during the first week. Patients with persistent late potentials (n = 9) on all three recordings in the first week showed a marked increase in end-diastolic volume index of 21.3 +/- 8.1 mL/m2 (P < .005 in comparison with patients who were persistently negative [n = 20]). Patients demonstrating dynamic positivity (n = 15) not present on all three recordings in the first week showed no significant increase in end-diastolic volume index. CONCLUSION: It is concluded that late potentials during the first week after infarction are associated with subsequent ventricular dilatation. These early-phase late potentials may be a manifestation of cell slippage. They arise before gross topographical enlargement and may serve as a predictor of ventricular dilatation. PMID- 8353918 TI - Slow conduction in the infarcted human heart. 'Zigzag' course of activation. AB - BACKGROUND: Ventricular tachycardias occurring in the chronic phase of myocardial infarction are caused by reentry. Areas of slow conduction, facilitating reentry, are often found in the infarcted zone. The purpose of this study was to elucidate the mechanism of slow conduction in the chronic infarcted human heart. METHODS AND RESULTS: Spread of activation was studied in infarcted papillary muscles from hearts of patients who underwent heart transplantation because of infarction. Recordings were carried out on 10 papillary muscles that were superfused in a tissue bath. High-resolution mapping was performed in areas revealing slow conduction. Activation delay between sites perpendicular to the fiber direction and 1.4 mm apart could be as long as 45 milliseconds. Analysis of activation times revealed that activation spread in tracts parallel to the fiber direction. Conduction velocity in the tracts was between 0.6 and 1 m/s. Although tracts were separated from each other over distances up to 8 mm, they often connected with each other at one or more sites, forming a complex network of connected tracts. In this network, wave fronts could travel perpendicular to the fiber direction. Separation of tracts was due to collagenous septa. At sites where tracts were interconnected, the collagenous barriers were interrupted. CONCLUSIONS: Slow conduction perpendicular to the fiber direction in infarcted myocardial tissue is caused by a "zigzag" course of activation at high speed. Activation proceeds along pathways lengthened by branching and merging bundles of surviving myocytes ensheathed by collagenous septa. PMID- 8353919 TI - The ability of several short-term measures of RR variability to predict mortality after myocardial infarction. AB - BACKGROUND: We studied 715 patients 2 weeks after myocardial infarction to test the hypothesis that short-term power spectral measures of RR variability (calculated from 2 to 15 minutes of normal RR interval data) will predict all cause mortality or arrhythmic death. METHODS AND RESULTS: We performed power spectral analyses on the entire 24-hour RR interval time series. To compare with the 24-hour analyses, we selected short segments of ECG recordings from two time periods for analysis: 8 AM to 4 PM and midnight to 5 AM. The former corresponds to the time interval during which short-term measures of RR variability would most likely be obtained. The latter, during sleep, represent a period of increased vagal tone, which may simulate the conditions that exist when patients have a signal-averaged ECG recorded, ie, lying quietly in the laboratory. Four frequency domain measures were calculated from spectral analysis of heart period data over a 24-hour interval. We computed the 24-hour power spectral density and calculated the power within three frequency bands: (1) 0.0033 to < 0.04 Hz, very low frequency power, (2) 0.04 to < 0.15 Hz, low frequency power, and (3) 0.15 to 0.40 Hz, high frequency power. In addition, we calculated the ratio of low to high frequency power. These measures were calculated for 15-, 10-, 5-, and 2 minute segments during the day and at night. Mean power spectral values from short periods during the day and night were similar to 24-hour values, and the correlations between short segment values and 24-hour values were strong (many correlations were > or = 0.75). Using the optimal cutpoints determined previously for the 24-hour power spectral values, we compared the survival experience of patients with low values for RR variability in short segments of ECG recordings to those with high values. We found that power spectral measures of RR variability were excellent predictors of all-cause, cardiac, and arrhythmic mortality and sudden death. Patients with low values were 2 to 4 times as likely to die over an average follow-up of 31 months as were patients with high values. The power spectral measures of RR variability did not predict arrhythmic or sudden deaths substantially better than all-cause mortality. CONCLUSIONS: Power spectral measures of RR variability calculated from short (2 to 15 minutes) ECG recordings are remarkably similar to those calculated over 24 hours. The power spectral measures of RR variability are excellent predictors of all-cause mortality and sudden cardiac death. PMID- 8353920 TI - Relation of plasma lipoprotein(a) to infarct artery patency in survivors of myocardial infarction. AB - BACKGROUND: In the minutes to days after myocardial infarction, endogenous lysis of an occlusive coronary arterial thrombus occurs in most subjects. Compared with those in whom thrombolysis does not occur, those with antegrade flow in the infarct artery have improved left ventricular performance, less left ventricular dilatation, and improved survival. This study was performed to assess intrinsic hemostasis and fibrinolysis in survivors of myocardial infarction with or without antegrade perfusion of the infarct artery. METHODS AND RESULTS: In 105 survivors of infarction (75 men, 30 women; age, 30 to 80 years) not given thrombolytic therapy, coronary angiography revealed a patent (group 1, n = 52) or occluded (group 2, n = 53) infarct artery. Plasma concentrations of plasminogen, fibrinogen, tissue plasminogen activator activity, infarct artery. Plasma concentrations of plasminogen, fibrinogen, tissue plasminogen activator activity, plasminogen activator inhibitor activity, cholesterol, triglycerides, and lipoproteins, including lipoprotein(a) (Lp[a]), were measured in blood procured 23 +/- 13 (mean +/- SD) months after infarction. Groups 1 and 2 were similar in age, sex, race, cardioactive medications, infarct artery, extent of coronary artery disease, and left ventricular performance. Of the plasma constituents assayed, the groups were similar except that Lp(a) averaged 18.5 +/- 21.7 mg/dL in group 1 and 49.1 +/- 44.8 mg/dL in group 2 (P < .001). This difference was evident in both Caucasian (n = 65) (P = .009) and African American (n = 40) (P = .01) subjects. CONCLUSIONS: Survivors of myocardial infarction who failed to recanalize the infarct artery have higher plasma Lp(a) concentrations than those with a patent infarct artery. Lp(a) may inhibit intrinsic fibrinolysis. PMID- 8353921 TI - Concordance and discordance between stress-redistribution-reinjection and rest redistribution thallium imaging for assessing viable myocardium. Comparison with metabolic activity by positron emission tomography. AB - BACKGROUND: Stress thallium scintigraphy provides important diagnostic and prognostic information in patients with coronary artery disease by demonstrating regional myocardial ischemia. However, if the clinical question being addressed is whether a region is viable and not whether there is inducible ischemia, then it may be more reasonable to perform rest-redistribution imaging rather than stress-redistribution imaging followed by either reinjection or late redistribution. Therefore, we determined whether stress-redistribution reinjection and rest-redistribution imaging provide the same information regarding myocardial viability. METHODS AND RESULTS: Both stress-redistribution reinjection and rest-redistribution thallium single photon emission computed tomographic imaging was performed in 41 patients with chronic stable coronary artery disease, with quantitative analysis of regional thallium activity. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution images were completed. Of the 155 myocardial regions with perfusion defects on the stress images, 91 (59%) were irreversible on conventional 3- to 4-hour redistribution images. When the outcomes of these irreversible regions were assessed after reinjection and compared with rest redistribution images, there was concordance of data regarding myocardial viability (normal/reversible or irreversible) in 72 of the 91 (79%) irreversible defects. Twenty of the 41 patients also underwent positron emission tomography at rest with [18F]fluorodeoxyglucose and [15O]water. In these patients, stress redistribution-reinjection and rest-redistribution imaging provided concordant information regarding myocardial viability in 427 (72%) of 594 myocardial regions and discordance in 167 regions. However, when irreversible thallium defects were further analyzed according to the severity of the thallium defect in these discordant regions, 149 of 167 (89%) demonstrated only mild-to-moderate reduction in thallium activity (51% to 85% of normal activity), and positron emission tomography verified 98% of these regions to be metabolically active and viable. Thus, when the severity of thallium activity was considered within irreversible thallium defects, the concordance between stress-redistribution-reinjection and rest-redistribution imaging regarding myocardial viability increased to 94%. CONCLUSIONS: These data indicate that one of two imaging modalities, either stress-redistribution-reinjection or rest-redistribution imaging, may be used for identifying viable myocardium. However, if there are no contraindications to stress testing, stress-redistribution-reinjection imaging provides a more comprehensive assessment of the extent and severity of coronary artery disease by demonstrating regional myocardial ischemia without jeopardizing information on myocardial viability. PMID- 8353922 TI - Relation of phasic coronary flow velocity profile to clinical and hemodynamic characteristics of patients with aortic valve disease. AB - BACKGROUND: Our objective was to assess phasic coronary blood flow and velocity characteristics of the proximal portion of the left anterior descending artery and to evaluate their relation to the clinical and hemodynamic manifestations in patients with aortic valve disease. METHODS AND RESULTS: We examined 26 patients with chronic aortic regurgitation (AR), 12 patients with predominant aortic stenosis (AS), and 11 control subjects using an intravascular Doppler catheter with spectral analysis. Angiographic assessment of AR identified 10 patients with mild regurgitation and 16 with severe regurgitation. The resting systolic coronary flow velocity-time integral (VTI) was significantly higher and the diastolic VTI was slightly but significantly higher in patients with severe regurgitation than in those with mild regurgitation (11.8 +/- 4.2 vs 4.1 +/- 1.1 cm, P < .001; 18.5 +/- 5.8 vs 13.2 +/- 3.2 cm, P < .05) and control subjects (4.0 +/- 1.0 cm, P < .001 and 13.3 +/- 3.6 cm, P < .05), respectively. Patients with AS had a slightly lower resting systolic VTI (3.8 +/- 1.4 cm) and a higher diastolic VTI (14.6 +/- 3.7 cm) than control subjects. Resting coronary blood flow was greater in patients with aortic valve disease than in control subjects. There was a significant correlation between the ratio of the resting systolic to diastolic VTI (S/D ratio) and the ratio of the aortic systolic to diastolic pressure (r = .75, P < .001) in patients with AR. The S/D ratio was inversely correlated with left ventricular systolic pressure (r = -.92, P < .001) and positively correlated with the ratio of the aortic systolic to diastolic pressure (r = .68, P < .05) in patients with AS. CONCLUSIONS: Our results indicate that hemodynamic changes related to aortic valve disease contribute to alterations in the resting phasic coronary blood flow and velocity profiles observed in these patients. PMID- 8353923 TI - Detailed angiographic analysis of high-speed mechanical rotational atherectomy in human coronary arteries. AB - BACKGROUND: Several types of atherectomy devices have been developed recently for treatment of patients with ischemic heart disease. METHODS AND RESULTS: Mechanical rotational atherectomy (MRA) using a high-speed rotational burr (Rotablator) was performed on 116 lesions in 104 patients. MRA alone was performed in 27 lesions (23%), and conventional balloon angioplasty (PTCA) was performed after MRA in 89 lesions (77%). Diameter stenosis decreased from 70 +/- 13% before MRA to 54 +/- 23% after MRA, and the final diameter stenosis (after MRA alone or with adjunctive PTCA) was 30 +/- 20% (P < .001). Minimal lumen diameter increased from 1.0 +/- 0.5 mm before MRA to 1.4 +/- 0.7 mm after MRA, and the final minimal lumen diameter was 2.3 +/- 0.7 mm (P < .001). MRA resulted in a decrease in diameter stenosis of 20% or more in 44% of lesions, and the final diameter stenosis (after MRA alone or after PTCA) was less than 50% in 75% of lesions. Considering the small diameter of available burrs, the magnitude of lumen enlargement was equal to 91% of the burr diameter, and only 9% of the burr diameter was "lost" due to elastic recoil or spasm. These angiographic results were obtained despite the presence of complex lesion morphology, including the presence of calcification in 17% of lesions and ostial location in 26% of lesions. Significant angiographic complications included abrupt closure (13 lesions, 11.2%), no reflow (8 lesions, 7%), severe coronary vasospasm (16 lesions, 13.8%), and guide wire fracture (3 lesions, 2.7%). There were no coronary artery perforations. Adjunctive therapy, including salvage PTCA, thrombolytic agents, and vasodilators, was successful in treating angiographic complications in 42 of 49 lesions (86%). Clinical complications included Q-wave myocardial infarction (5 patients, 4.8%), non-Q-wave myocardial infarction (3 patients, 2.9%), femoral vascular injury requiring surgery (3 patients, 2.9%) or blood transfusion (8 patients, 7.7%), abrupt closure requiring emergency bypass graft surgery (2 patients, 1.9%), and in-hospital death (1 patient, 1.0%). Angiographic follow-up (mean follow-up interval, 5.0 +/- 2.0 months) was available in 84% of successfully treated patients and revealed a restenosis rate of 51%, defined as a residual diameter stenosis of more than 50%. There was no significant difference in restenosis rates between de novo lesions (50%) and restenosis (54%) lesions. CONCLUSIONS: These data suggest that for the treatment of most coronary stenoses, PTCA is required after MRA to achieve satisfactory lumen enlargement or to salvage complications. Angiographic complications appear to be more common after MRA, and salvage PTCA often is required to manage these device-induced complications. The combination of MRA and PTCA does not prevent restenosis. PMID- 8353924 TI - Restenosis rate after multiple percutaneous transluminal coronary angioplasty procedures at the same site. A quantitative angiographic study in consecutive patients undergoing a third angioplasty procedure for a second restenosis. AB - BACKGROUND: Several studies suggest that repeated percutaneous transluminal coronary angioplasty procedures at the same site are associated with a progressively increasing risk of further restenosis and that short time intervals between successive procedures are predictive of future restenosis. METHODS AND RESULTS: We assessed by quantitative coronary angiography the angiographic probability of restenosis when repeat percutaneous transluminal coronary angioplasty was performed at a site where restenosis had occurred after two previous angioplasty procedures. Of 99 consecutive patients who underwent a third angioplasty procedure, 96 had successful procedures. Uncomplicated failure (residual stenosis > or = 50%) occurred in 3 patients. No major complications occurred. Follow-up angiography was routinely advised; it was performed in 83 patients (86%) with successful procedures. Restenosis (recurrence of > or = 50% stenosis determined by quantitative coronary angiography) occurred in 32 patients (39%). An interval of < 3 months between the second and third angioplasty was strongly associated (P < .005) with the occurrence of further restenosis after a third procedure. CONCLUSIONS: The angiographic probability of further restenosis after three successive angioplasty procedures at the same site is similar to that reported after a first angioplasty procedure in studies that used a similar definition of restenosis. Patients who undergo a third angioplasty procedure within 3 months of a previous procedure at the same site have a much higher risk of subsequent restenosis. This easily identified subgroup may benefit from an alternative therapeutic approach. PMID- 8353925 TI - Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factors related to long-term angiographic outcome. Coronary Artery Restenosis Prevention on Repeated Thromboxane Antagonism (CARPORT) Study Group. AB - BACKGROUND: The renarrowing process after successful percutaneous transluminal coronary angioplasty (PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The aim of the present study was to find independent patient-related, lesion-related, and procedure related risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen diameter. This population could then constitute the target population for pharmacological intervention studies. METHODS AND RESULTS: Quantitative angiography was performed on 666 successfully dilated lesions at angioplasty and at 6-month follow-up. Multivariate linear regression analysis was performed to obtain variables with an independent contribution to the prediction of the absolute change in minimal lumen diameter. Diabetes mellitus, duration of angina < 2.3 months, gain in MLD at angioplasty, pre-PTCA MLD, lesion length > or = 6.8 mm, and thrombus after PTCA were independently predictive of change in MLD. Overall prediction of the model was poor, however, percentage-correct classification for a predicted change between -0.1 to -0.4 mm was approximately 10%. Lesions showing no change or regression (change > -0.1 mm) and lesions showing large progression (< or = -0.4 mm) were more predictable (correct classification, 59.5% and 49.7%, respectively). CONCLUSIONS: Renarrowing after successful PTCA as determined with contrast angiography is a process that cannot be accurately predicted by simple clinical, morphological, and lesion characteristics. PMID- 8353926 TI - Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events. AB - BACKGROUND: In essential hypertension, a blunted or absent nocturnal fall in blood pressure (BP) may be associated with increased target organ damage. In this case-control study, we tested the hypothesis that an association exists between a blunted or absent nocturnal fall in BP and future cardiovascular morbid events in patients with essential hypertension. METHODS AND RESULTS: Case subjects were 32 hypertensive patients with a first fatal or nonfatal major cardiovascular event who had off-therapy ambulatory BP monitoring 1 to 5 years earlier in the context of a registry of morbidity and mortality in hypertensive patients. Control subjects were 49 hypertensive patients free from cardiovascular events. The groups were matched with regard to date of baseline ambulatory BP monitoring, age, sex, clinic systolic and diastolic BP, and daytime ambulatory systolic and diastolic BP. At their baseline evaluation, cases and controls did not differ, in either sex, with respect to clinic BP (men, 164/100 vs 162/99 mmHg; women, 178/96 vs 180/93 mmHg), mean daytime ambulatory BP (men, 151/94 vs 147/95 mm Hg; women, 156/90 vs 158/89 mm Hg), age (men, 55 vs 56 years; women, 69 vs 68 years), sex, body weight, serum cholesterol, known duration and family history of hypertension, smoking habits, renal function, or prevalence of diabetes. Echocardiographic left ventricular mass, determined in a subset of patients, was greater in cases than in controls in men (145 vs 115 g/m2, P = .038) and women (137 vs 102 g/m2, P = .032). The time interval between baseline ambulatory BP monitoring and subsequent cardiovascular event (cases: mean, 2.1 years) or last contact with our center (controls: mean, 2.5 years) did not differ between the groups. In the baseline ambulatory BP profile, the nocturnal reductions of systolic and diastolic BP in men were 9% and 11%, respectively, in cases vs 9% and 12% in controls (all P = NS), whereas in women they were 3% and 8% in cases vs 11% and 16% in controls (P = .002/.004). CONCLUSIONS: This retrospective case control study suggests an association between the reduction or absence of the usual nocturnal fall in BP and future cardiovascular morbid events in white women with essential hypertension. PMID- 8353928 TI - Changes in dendritic morphology of rat spinal motoneurons during development and after unilateral target deletion. AB - During normal development, motoneuron dendrites in the spinal nucleus of the bulbocavernosus (SNB) grow exuberantly to almost twice their adult length and then retract. In this study, we retrogradely labeled SNB motoneurons with cholera toxin B-conjugated horseradish peroxidase (BHRP) to examine the maturation of SNB dendritic arbors in more detail, particularly with regard to its spatial distribution and reorganization. The number and orientation of SNB motoneuron primary processes did not change over the first ten weeks of life. In contrast, total dendritic length, radial extent and arbor area increased significantly through the first four postnatal weeks and declined thereafter. The declines in length and extent were restricted to particular portions of the arbor, specifically the dorsal, ipsi- and contralateral projections. Estimates of the degree of overlap between the dendritic arbors from both sides of the SNB reflected these changes, with overlap initially increasing and then decreasing as the SNB established its adult dendritic morphology. To determine if dendritic interactions facilitated by this arbor overlap might be involved in regulating the normal retraction of SNB dendrites, we reduced SNB motoneuron numbers unilaterally by target muscle removal on the day of birth. Somal size, number and orientation of primary processes developed normally in unilateral muscle extirpated animals. The dendritic morphology of surviving SNB motoneurons in unilateral muscle extirpated males was altered, with significant increases in dendritic length, extent and arbor area relative to those of normal males. These results indicate that substantial changes in dendritic organization of SNB motoneurons occur in normal development and may be influenced by interactions between dendrites from the two halves of the SNB. PMID- 8353927 TI - Structural and functional alterations of the intramyocardial coronary arterioles in patients with arterial hypertension. AB - BACKGROUND: In hypertensive patients with angina pectoris, the coronary vasodilator reserve is frequently impaired despite a normal coronary angiogram. Experimental data indicate that structural alterations of the intramyocardial coronary vasculature contribute to an increased minimal coronary resistance and a diminished coronary flow reserve. METHODS AND RESULTS: In 14 patients (10 men and 4 women) with arterial hypertension and 8 normotensive subjects, minimal coronary resistance and vasodilator reserve (dipyridamole: 0.5 mg/kg body wt, gas chromatographic argon method) were determined after the angiographic exclusion of relevant coronary artery disease. Coronary reserve was depressed in hypertensive patients (2.7 +/- 2.3 vs 4.6 +/- 1.3, P < or = .05) due to increased minimal coronary resistance (0.64 +/- 30 vs 0.24 +/- 0.055 mm Hg.min.100 g.mL-1, p < or = 0.002). In right septal biopsies, mean external arteriolar diameter (21.6 +/- 2.3 vs 17.2 +/- 2.5 microns, P < or = .001), mean arteriolar wall area (271 +/- 61 vs 172 +/- 62 microns 2, P < or = .01), percent medial wall area (69.9 +/- 4.0 vs 66.0 +/- 3.2%W, P < or = .05), mean periarteriolar fibrosis area (216 +/- 122 vs 104 +/- 68 microns 2, P < or = .05), and volume density of total interstitial fibrosis (3.6 +/- 1.8 vs 1.9 +/- 0.5Vv% fibrosis, P < or = .05) were increased in hypertensive patients compared with normotensive subjects. Minimal coronary resistance correlated with %W (r = .6, P < or = .003) and Vv% fibrosis (r = .62, P < or = .002). Left ventricular mass index (111 +/- 21 vs 97 +/- 17 g/m2, P = NS) and left ventricular end-diastolic pressure (12 +/- 6 vs 8 +/- 3 mm Hg, P = NS) did not correlate significantly with minimal coronary resistance. In multivariate analysis, both %W and Vv% fibrosis explained half of the variability of minimal coronary resistance (r2 = .5, P < or = .002). CONCLUSIONS: Structural remodeling of the intramyocardial coronary arterioles and the accumulation of fibrillar collagen are decisive factors for a reduced coronary dilatory capacity in patients with arterial hypertension and angina pectoris in the absence of relevant coronary artery stenoses. PMID- 8353929 TI - The effect of nerve growth factor on cholinergic cells in primary fetal striatal cultures: characterization by in situ hybridization. AB - In situ hybridization using 35S-labeled antisense oligonucleotide probes for choline acetyltransferase (ChAT), and m1 and m2 muscarinic receptors was employed to monitor the effect of nerve growth factor (NGF) on cholinergic cells in mixed neuronal-glial striatal brain cultures prepared from E16/E17 rat embryos. In cultures treated with NGF, cells reactive to the ChAT oligonucleotide probe were significantly larger than cells in untreated cultures. In addition, there was a significant increase in the number of silver grains over reactive cells in cultures exposed for 9-10 days to exogeneous NGF. Similar results were obtained with an oligonucleotide probe specific for m2 muscarinic receptors: in NGF treated cultures, cells reactive to the m2 receptor probe were significantly larger and had more silver grains than cells from non-treated cultures. On the other hand, no significant effect of NGF on cell size or on the number of grains was observed for cells reactive to an m1 muscarinic receptor probe. These results demonstrate that NGF specifically increases the transcription of genes (ChAT and m2 muscarinic receptor) the expression of which is associated with cholinergic neurons, promoting the growth of this particular type of neuron. PMID- 8353930 TI - Differential timing and sexual dimorphism in the expression of the vasopressin gene in the developing rat brain. AB - The ontogeny of vasopressin (VP) gene expression in extrahypothalamic neurons of the bed nucleus of the stria terminalis (BNST) and medial amygdala (MA) was investigated using in situ hybridization. In both the BNST and MA, VP mRNA positive cell profiles were only detected a few days after birth. In males, VP mRNA-expressing cell profiles appear in the BNST on day 3 and in the MA on day 5. In contrast, hybridization signals could not be detected in the female brain until day 14 in the BNST and day 35 in the MA. Adult VP mRNA levels are attained by day 35 in the BNST and day 60 in the MA for both sexes. From this data, it is apparent that development of the VP system is delayed in females compared to the males. Therefore, these data suggest that the sexual dimorphic pattern in the expression of VP mRNA in these nuclei of the adult brain is evident early in the development process. PMID- 8353931 TI - Excitatory amino acid regulation of the enkephalin phenotype in mouse embryonic spinal cord cultures. AB - Expression of the preproenkephalin gene in developing spinal cord-dorsal root ganglia (SC-DRG) cultures was determined by Northern analysis following treatments with different agonists and antagonists of the glutamate receptor. Cultures (10-12 days old) were treated with various concentrations (10(-7)-10(-3) M) of N-methyl-D-aspartate (NMDA), quisqualate, kainic acid (KA), 2-amino-5 phosphonovaleric acid (APV) and 5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate (MK801) either with or without blocking spontaneous electrical activity with 1 microM tetrodotoxin (TTX). In electrically active cultures, treatments with NMDA and KA increased preproenkephalin transcripts (mRNAppENK), showing maximum effects at 1 microM (4-fold and 2-fold, respectively), while treatments with quisqualate and MK801 caused concentration dependent down-regulation in mRNAppENK. The most effective concentrations of NMDA (1 microM) and quisqualate (10 microM) altered mRNAppENK levels within 4 h of treatment and peaked after 24 h for NMDA and 48 h for quisqualate treatment. Co treatment with APV completely blocked the NMDA-induced rise of mRNAppENK. During electrical blockade, none of the concentrations of NMDA tested showed any effect on enkephalin expression, neither could NMDA pre-treatment prevent the TTX induced down-regulation of mRNAppENK. Our results indicate that the activity dependent establishment of the enkephalin phenotype is modulated through the selective activation of the NMDA-glutamate receptor. PMID- 8353932 TI - Age- and dose-related NMDA induction of Fos-like immunoreactivity and c-fos mRNA in the arcuate nucleus of immature female rats. AB - Glutamate and the N-methyl-D-aspartate (NMDA) receptor are important regulatory components of the hypothalamic control of luteinizing hormone (LH) secretion. Peripheral injection of prepubertal rats with NMDA induces maximal secretion of LH within 8 min as well as the expression of the proto-oncogene, c-fos, within the mediobasal hypothalamus (MBH). Because the induction of the c-fos gene is recognized as a sensitive marker of neuronal activity, the detection and characterization of c-fos mRNA and Fos protein may be particularly useful in the analysis of the GnRH (gonadotropin releasing hormone) neuronal system. This study has examined the effect of different doses of NMDA on c-fos mRNA and Fos-like immunoreactivity (Fos-lir); the time-course of induction of c-fos mRNA and the appearance of Fos-lir expression and the ontogeny of NMDA-induced Fos-lir. Our results indicate that NMDA-induced c-fos mRNA and protein are maximal by 60 and 120 min, respectively. Both c-fos mRNA and protein attain peak levels using NMDA doses between 20 and 40 mg/kg. Ontological studies demonstrated that Fos-lir could be detected at 5 days after birth, but declined after sexual maturation. The data presented here indicate that the immunohistochemical localization of c fos gene expression, in conjunction with in situ hybridization, is a useful technique for mapping NMDA-sensitive pathways and may provide anatomical and physiological evidence that better defines the glutamatergic control of sexual maturation. PMID- 8353933 TI - Developmental regulation of neuronal expression for the eta subtype of the 14-3-3 protein, a putative regulatory protein for protein kinase C. AB - An in situ hybridization technique was applied to rat nervous tissues, to analyse the developmental changes in expression for the eta subtype mRNA of 14-3-3 protein, a putative regulatory protein for protein kinase C. Although signal levels of the eta subtype mRNA were low in mitotic cells in the ventricular zone, most neurons displayed a marked increase at their definitive location in the mantle zone. In general, neurons in the spinal ventral horn and peripheral ganglia showed this increase at E13-E15, those in the telencephalon, diencephalon, midbrain, pons and medulla oblongata at E18-P1, and the cerebellar Purkinje cells at P7-P14. It is at these developmental stages when neuronal differentiation including axonal and dendritic growth and ramification occurs actively. Subsequently high levels of the eta subtype mRNA were maintained until the adult stage in projection type neurons possessing larger cell bodies and highly developed dendritic fields, such as the olfactory mitral cells, hippocampal pyramidal cells, cerebellar Purkinje cells, and motor neurons in the brainstem and spinal cord. However, the signal levels decreased until the adult stage in smaller projection type neurons. On the other hand, the signal levels in local circuit type neurons were consistently low throughout development. These findings suggest that gene expression for the eta subtype mRNA of the 14-3-3 protein is regulated in close relation to both neuron types and their cytodifferentiation. PMID- 8353934 TI - S-adenosylmethionine decarboxylase in human brain. Regional distribution and influence of aging. AB - Recent experimental animal studies have implicated brain polyamines as having roles in both brain development and human brain neurodegenerative conditions. In order to provide baseline information, in normal human brain, on one of the key polyamine synthesising enzymes, S-adenosylmethionine decarboxylase (SAMDC), we examined the sensitivity of this enzyme to various cofactors/inhibitors, its regional distribution, and influence of aging in neurologically normal autopsied human brain. SAMDC in normal human brain is similar to that reported in other mammalian cells with regard to substrate affinity (Km = 39 microM), marked sensitivity to putrescine activation (+600%), inhibition (methylglyoxalbisguanidine and MDL 73811), and pH optimum (7.2). There was an uneven distribution of enzyme activity in human brain, and of the 12 brain regions examined, the highest activity was observed in occipital, parietal, frontal and temporal cortices (36-58 pmol/h/mg protein); intermediate activity in cerebellar and insular cortex, pulvinar thalamus, caudate and putamen (12-27 pmol/h/mg protein); and lowest activity in medial-dorsal thalamus, lateral globus pallidus and white matter (< 11 pmol/h/mg protein). The influence of aging (1 day to 103 years) on SAMDC activity in occipital cortex, the region showing the highest activity in human brain (n = 59) was also determined. Enzyme activity increased by approximately 600% from age 6 months to near maximal levels at age 10 years, then remained generally unchanged up to 103 years. Since SAMDC is a key regulatory enzyme in the synthesis of spermidine and spermine, the marked increase in SAMDC activity in the neonate and the sustained high enzyme levels throughout adulthood, imply a role for these polyamines in both development and mature brain function. PMID- 8353935 TI - Effects of a specific glucocorticoid receptor antagonist on corticotropin releasing hormone gene expression in the paraventricular nucleus of the neonatal rat. AB - Mechanisms controlling the synthesis of corticotropin releasing hormone (CRH) in neonatal rats, and the ontogeny of glucocorticoid (GC) feedback control of hypothalamic CRH remain unknown. Specific issues are whether stress induces up regulation of CRH gene expression during the first postnatal week, and the role of GC feedback, at the hypothalamic level, in the stress-hyporesponsive period. We studied the ontogeny of the negative feedback regulation of CRH gene expression by GC in the paraventricular nucleus (PVN). We implanted chronic cannulae containing a GC-receptor antagonist, RU 38486, in rats on postnatal days 3 to 13. Three days later, animals were sacrificed, and brains were analyzed for CRH-messenger RNA (CRH-mRNA), using semi-quantitative in situ hybridization. Animals implanted with cholesterol-containing cannulae served to evaluate the stressful effect of implantation on CRH-mRNA abundance. The presence of GC receptor messenger RNA (GR-mRNA) in the PVN of neonatal rats was also determined. RU 38486 did not increase CRH-mRNA abundance during the first postnatal week, despite the presence of GR-mRNA in the PVN. Chronic-implantation stress also failed to increase CRH synthesis. CRH gene expression in the PVN was enhanced in infant rats implanted with RU-38486 on postnatal day 9 or later. Cholesterol implantation on days 9, 10 (but not later), resulted in increased PVN-CRH-mRNA. Thus, CRH-mRNA is up-regulated by chronic blockade of GC receptors only subsequent to the eighth postnatal day. Furthermore, such blockade does not affect the response of CRH-mRNA to chronic stress in the neonatal rat. PMID- 8353936 TI - Large chondroitin sulfate proteoglycans of developing chick CNS are expressed in cerebral hemisphere neuronal cultures. AB - Chondroitin sulfate proteoglycans (CSPG) of the extracellular matrix may play regulatory roles in central nervous system (CNS) development. We have examined the expression of two large CSPGs of the embryonic chick brain, which can be differentiated using the monoclonal antibodies HNK-1 and S103L, in cultures of embryonic day 6 chick cerebral hemisphere neurons. Western blot analysis following immunoprecipitation and endoglycosidase treatment revealed that these cultures produce S103L- and HNK-1-reactive proteoglycans which are biochemically indistinguishable from the CSPGs (previously) identified in homogenized chick embryo brain extracts. The HNK-1-reactive CSPG accumulated in the medium throughout the course of cultures. In contrast, the S103L-reactive CSPG was found in a neuron-associated form during the period of aggregate establishment in culture, as well as in a soluble form secreted into the medium. Immunocytochemical staining of cultures with the S103L antibody localized reactivity to most neurons during the period of aggregate formation, while neuronal processes and the few flat cells present (presumably neuroblasts and early glia) were negative. Cell selection experiments confirmed that neurofilament-positive cells were the source of the S103L-reactive CSPG. The use of differential fixation techniques suggested that the cell-associated S103L reactivity may be intracellular. Because of this pattern of expression and localization, we propose that the developmentally regulated S103L-reactive CSPG may play a role in neuronal migration arrest and organization of neurons into functional aggregates. PMID- 8353937 TI - Ontogeny of Leu-enkephalin and beta-endorphin innervation of the preoptic area in male and female rats. AB - The distribution of endogenous opioid peptide-containing fibers in the medial preoptic area of developing male and female rats was examined using immunohistochemical methods. In particular, the ontogeny of leucine-enkephalin (leu-enk) and beta-endorphin (beta-endo) innervation was studied using antisera directed against these compounds. The distribution of Leu-enk and beta-endo differed at each age examined from birth to postnatal day 12 (P12). Furthermore, the patterns of fiber innervation differed across development. Leu-enk-like immunoreactivity was initially densest in the lateral preoptic region of both sexes, ultimately expanding into the medial preoptic region to become densest in the lateral portion of the medial preoptic nucleus by P12. This latter pattern was observed only in males, however, as females continued to exhibit diffuse medial preoptic Leu-enk-like immunoreactivity at P12. In contrast, the distribution and developmental pattern of beta-endo-like immunoreactivity was similar in both sexes; diffuse staining was observed in the medial preoptic region at birth, later becoming dense only in the periventricular and parastrial nuclei. The time course of development of Leu-enk and beta-endo innervation of the medial preoptic area suggests that the sexually dimorphic expression of opioid immunoreactivity occurs after preoptic neurons appear in their sexually dimorphic configuration. Therefore, although the development of opioid-containing pathways could be influenced by the perinatal gonadal steroid hormone environment, medial preoptic Leu-enk and beta-endo innervation might not contribute directly to the sexually dimorphic neuronal organization of the preoptic area. PMID- 8353938 TI - Cocaine depresses cerebral glucose utilization in fetal sheep. AB - To assess if cocaine alters cerebral glucose metabolism in the fetus, we infused cocaine 0.6 mg/min intravenously to 6 of 13 fetal sheep for the 55 min prior to measurement of glucose utilization by an autoradiographic method. Overall, local cerebral glucose utilization (LCGU) was lower in cocaine-exposed fetuses than in 7 controls (P = 0.058). In the cocaine-exposed fetuses, 33 of 34 structures had lower mean LCGU than in the comparable structures of control fetuses. In addition, the autoradiographs in 4 of 6 cocaine-exposed fetuses revealed thin, dark lines of increased glucose utilization within the central white matter of some frontal gyri which were not seen in any of the 7 control fetuses. These lines were distributed similarly to ones seen earlier in severely hypoxic newborn lambs. In fetal lambs, cocaine resulted in a generalized decrease in LCGU and a specific increase in glucose utilization in parts of cortical white matter of the frontal gyri, possibly secondary to local ischemia. PMID- 8353939 TI - Rapid plastic response following early retinal lesions in rats. AB - Following an early retinal lesion, aberrant uncrossed projections from the opposite, undamaged, retina form in the target visual nuclei. The present study has examined the development of such aberrant projections by making retinal lesions in newborn rat pups, and then examining the nature of the uncrossed retinocollicular projection at different ages following the lesion. Intravitreal injections of horseradish peroxidase were made into the intact eye, and the uncrossed projection was subsequently revealed histochemically. A mature aberrant projection forms as early as postnatal day 9. On postnatal days 5 and 2, aberrant projections are discernable amongst the exuberant uncrossed terminals of normal developing rats, although the former have not matured to form the dense terminal fields characteristic of older projections. Aberrant projections were also detectable as early as 12 h following the lesion, revealed as a relative increase in the density of uncrossed label. These results indicate that lesion-induced plastic responses by intact retinal arbors are initiated shortly after the insult, and they caution the use of retinal lesions in studies of normal retinotopic connectivity during development. PMID- 8353940 TI - More rapid biochemical diagnosis of myocardial infarction: necessary? Prudent? Cost effective? PMID- 8353941 TI - Spectrophotometry of hemoglobin: various perspectives. PMID- 8353942 TI - Homocysteine and other thiols determined in plasma by HPLC and thiol-specific postcolumn derivatization. AB - We describe a versatile high-performance liquid-chromatographic method for determining homocysteine and other plasma sulfhydryls. Using three different procedures for preparation of plasma, we determined total, free (non-protein bound), and reduced forms of homocysteine, cysteine, glutathione, cysteinylglycine, and gamma-glutamylcysteine in human plasma. Sample preparation involves disulfide reduction with dithiothreitol and protein precipitation with sulfosalicylic acid. The assay utilizes isocratic reversed-phase ion-pair liquid chromatography at pH 2.4, postcolumn derivatization with 4,4'-dithiodipyridine, and colorimetric detection at 324 nm. The intra-assay precision (CV) of the method for total homocysteine is 1.5%; the interassay precision over 2.5 months is 2.5%. The detection limit for homocysteine is < 50 nmol/L plasma. PMID- 8353943 TI - Recombinant creatine kinase proteins and proposed standards for creatine kinase isoenzyme and subform assays. AB - We developed standards for creatine kinase (CK; EC 2.7.3.2) assays by expressing human CK cDNAs in COS cells. Cells were transiently transfected with full-length cDNAs for CK subunits M and B, individually and in combination; and subsequently, high concentrations of CK activity were present in the cell lysate (1.2 U/mg protein). These proteins exhibited the characteristic isoenzyme-specific electrophoretic mobilities for CK MM and BB isoenzymes. We also produced subforms of CK MM and MB, identical to the modified CK variants produced in plasma after muscle or myocardial injury, by mutating the cDNA for the CK M subunit to delete the carboxy-terminal lysine residue. When this construct was cotransfected with the normal cDNAs for CK M and B, five electrophoretically distinct CK isoenzymes were detected by nondenaturing electrophoresis: MM3, MM2, MM1, MB2, and MB1. These proteins retained 100% of their activity after storage of the cell lysates 20 or 4 degrees C for 3 months. PMID- 8353944 TI - Serum cholesterol determined by liquid chromatography with 6-chlorostigmasterol as internal standard. AB - We describe an accurate and precise method for determining serum cholesterol by high-performance liquid chromatography (HPLC). After addition of 6 chlorostigmasterol as internal standard, serum is treated with alcoholic potassium hydroxide. Subsequently the cholesterol and internal standard are extracted from the mixture into n-hexane and then derivatized to phenylurethanes for measurement by HPLC with ultraviolet detection. The effective chromatographic separation and the use of an appropriate internal standard make this procedure free from interferences by other serum sterols and precise. The mean cholesterol concentration in Standard Reference Material (SRM) 909 (human serum) assayed by this procedure (4.346 mmol.g-1 x L-1) agreed well with the value assigned by the National Institute of Standards and Technology (4.359 mmol.g-1 x L-1). Within-run and total CVs were 0.56% and 0.78%, respectively. Therefore the performance of this procedure is sufficiently good to allow its use as a candidate reference method for serum cholesterol determination. PMID- 8353945 TI - Calcium determination in serum with stable alkaline Arsenazo III and triglyceride clearing. AB - We describe an analytical procedure for determining serum calcium, using the ligand Arsenazo III in an aqueous alkaline medium. The choice of pH for the proposed technique differs from current procedures, which are for the most part carried out in a slightly acidic medium. An acidic medium avoids interference from magnesium, but is spectrophotometrically suboptimal for this pH-dependent reaction: the molar absorptivity of the Arsenazo III complex with calcium at acid pH is 13,787 L mol-1 cm-1, about one-half of that at a more optimal alkaline pH (26,574 L mol-1 cm-1). We have included a clearing technique in the reagent to avoid spectral aberrations from hypertriglyceridemic samples. alpha-Cyclodextrin absorbs the nonesterified fatty acids liberated from triglycerides by a microbial lipase. This modification may also be helpful for binding nonesterified fatty acids, which are known to interfere with calcium procedures by forming calcium soaps and thus preventing the reaction with intended ligands. The use of 8 hydroxyquinoline sulfonate as the magnesium-masking agent facilitates the use of alkaline pH. The less-water-soluble alternative, 8-hydroxyquinoline, commonly used as a precipitating agent for several methods, is difficult to solubilize in the alkaline reagent and tends to precipitate when complexed to magnesium. Finally, the use of alkaline pH results in a prolonged (> or = 6 weeks) shelf life for the reagent. PMID- 8353946 TI - Creatine measurement in serum and urine with an automated enzymatic method. AB - I describe an automated enzymatic procedure to quantitate creatine in both serum and urine. In this assay, which requires no pretreatment of the sample, creatine kinase (CK; EC 2.7.3.2) and pyruvate kinase (EC 2.1.7.40) are used as auxiliary enzymes and lactate dehydrogenase (EC 1.1.1.27) is used in the indicator reaction. CK is also used as the starting reagent. Data obtained with the present method for creatine measurement in serum were compared with those from the Jaffe method and an enzymatic method: y = 1.13x - 7.58, SE = 4.48, and r = 0.925 (Jaffe); and y = 1.17x + 2.73, SE = 5.06, and r = 0.962 (enzymatic); for creatine measurement in urine: y = 0.63x + 39.74, SE = 296.7 and r = 0.719 (Jaffe). The present method provides improved precision: the total CVs for serum, determined by the present and comparative methods, respectively, were 3.5-8.9%, 8.2-43.0%, and 5.3-16%; for urine, the CVs were 3.3-5.1% and 9.6-21.2% for the present and comparative method, respectively. I established the normal reference interval as 13-74 and 13-89 mumol/L for creatine in serum, and as 175-700 and 150-1200 mumol/24 h for creatine in urine for men and women, respectively. PMID- 8353947 TI - Time-resolved immunofluorometric assay of human growth hormone. AB - We describe a time-resolved immunofluorometric assay (trIFMA) for human growth hormone (hGH), in which monoclonal antibody (mAb)-coated microtiter strip wells and a europium (Eu) chelate-labeled mAb are used. We compare the new trIFMA, in which two mAbs are used, with an immunoradiometric assay (IRMA) in which polyclonal antibodies are used. Serum samples (n = 185) from 36 children with various diagnoses were analyzed. In addition, 24-h profile samples (72 per child) from 39 children were analyzed. The trIFMA was more sensitive (detection limit, 0.03 mIU/L) than existing IRMAs. Both the intra- and interassay CVs were < or = 10.6% for hGH concentrations between 1 and 100 mIU/L. The trIFMA is technically simple and rapid, requires no centrifugation or separation reagent, and has a counting time of only 1 s per sample. In addition, the Eu label is nontoxic, presents no waste-disposal problems, and has a long shelf-life. Finally, the assay requires only small volumes of serum (25 muL), which is of considerable importance in pediatric use. The mAbs used for the trIFMA selectively bind the 22 kDa form of hGH, with the result that the assay detects about 80% of the amount detected by the polyclonal IRMA. PMID- 8353948 TI - Europium-labeled oligonucleotides to detect point mutations: application to PIZ alpha 1-antitrypsin deficiency. AB - We describe a novel assay for detection of point mutations. The method combines the specificity and sensitivity of the polymerase chain reaction (PCR) and allele specific oligonucleotides (ASO) with highly sensitive time-resolved fluorometry. ASO probes differing by a single base substitution and labeled with europium (Eu) chelates were hybridized in solution simultaneously with a biotinylated oligomer to a PCR-amplified nucleic acid fragment. The hybrids formed were then collected onto streptavidin-coated microtitration wells. Subsequently, the hybrids were washed under stringent conditions and the remaining ASO probe was measured in a time-resolved fluorometer. We discuss the strategy underlying the design of the Eu-labeled ASO probes for the solution hybridization assay. The method was applied to the detection of the Z-mutation in the alpha 1-antitrypsin gene. Evaluation of whole-blood samples spotted on Guthrie cards demonstrated successful accuracy of the method. PMID- 8353949 TI - Profiles of very-long-chain fatty acids in plasma, fibroblasts, and blood cells in Zellweger syndrome, X-linked adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata. AB - Profiles of saturated very-long-chain (> C22) fatty acids were studied in plasma, fibroblasts, erythrocytes, platelets, and leukocytes of patients affected by peroxisomal disorders such as Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD), and classic rhizomelic chondrodysplasia punctata (RCDP) and in controls. In Zellweger patients, the concentration of hexacosanoic acid (C26:0) and the C26:0/C22:0 ratio are greatly increased in plasma and fibroblasts. However, the plasma concentration of docosanoic acid (C22:0) is greatly decreased. Also in platelets, leukocytes, and to a lesser extent erythrocytes, the C26:0 concentrations and both the C26:0/C22:0 and C24:0/C22:0 ratios are greatly increased. The C24:0/C22:0 ratio is significantly increased in plasma, platelets, and leukocytes, but not in erythrocytes. In X-ALD, the C26:0 concentration and the C26:0/C22:0 and C24:0/C22:0 ratios are significantly increased in plasma, fibroblasts, platelets, and leukocytes, but the erythrocytes show substantial overlap in the 5-90% ranges between controls and patients. In RCDP, slightly increased C26:0 and C26:0/C22:0 ratios are found in erythrocytes, platelets, and leukocytes, but not in plasma and fibroblasts. We conclude that plasma and fibroblasts are the specimens of choice for biochemical diagnosis of Zellweger syndrome and X-ALD, respectively. The slight increase in C26:0 in blood cells of RCDP patients suggests a decreased flux of very-long-chain fatty acids through the peroxisomal beta-oxidation pathway in liver in this genetic disorder. PMID- 8353950 TI - Comparison of quality-control rules used in clinical chemistry laboratories. AB - Numerous papers have been written to show which combinations of Shewhart-type quality-control charts are optimal for detecting systematic shifts in the mean response of a process, increases in the random error of a process, and linear drift effects in the mean response across the assay batch. One paper by Westgard et al. (Clin Chem 1977;23:1857-67) especially seems to have attracted the attention of users. Here we derive detailed results that enable the characteristics of the various Shewhart-type control schemes, including the multirule scheme (Clin Chem 1981;27:493-501), to be calculated and show that a fundamental formula proposed by Westgard et al. in the earlier paper is in error, although their derived results are not seriously wrong. We also show that, from a practical point of view, a suitably chosen Cusum scheme is near optimal for all the types and combinations of errors discussed, thereby removing the selection problem for the user. PMID- 8353951 TI - Trace elements determined along single strands of hair by inductively coupled plasma mass spectrometry. AB - Flow injection-inductively coupled plasma mass spectrometry has been evaluated for determining the distribution profile of trace elements along a single strand of hair. Hair was cut into several mm long sections from follicle to the distal end. Each section was solubilized in a capped 1.5-mL polypropylene tube with small volume of nitric acid (typically 50 microL) at room temperature. After dilution an aliquot (50 microL) was introduced into the mass spectrometer by flow injection. The limit of determination was typically 5-50 pg with 5-10% precision (CV), depending on the element examined; this corresponds to sub-microgram/g concentrations of these elements in hair segments. Recent exposure and intake history of individuals to thallium or mercury could be reconstructed by this system. PMID- 8353952 TI - Determination of clozapine, norclozapine, and clozapine-N-oxide in serum by liquid chromatography. AB - We report a new assay to measure the serum concentrations of the atypical antipsychotic drug clozapine and two major metabolites, norclozapine and clozapine-N-oxide. The analytes and an internal standard (triprolidine) were extracted from alkalinized samples into ethyl acetate and back-extracted into 0.1 mol/L HCl. The acid extracts were chromatographed on a reversed-phase liquid chromatographic column with photodiode array detection (210-340 nm). With the 254 nm signal, between-run imprecision (CV) was < 2% for clozapine and norclozapine at 400 micrograms/L, and 4.1% for clozapine-N-oxide at 100 micrograms/L. Absolute recovery exceeded 65%, and the detection limit was approximately 3-4 micrograms/L. In 25 patients at steady state at a mean daily clozapine dosage of 269 mg (3.09 mg/kg), clozapine averaged 231 +/- 144 micrograms/L (mean +/- SD); norclozapine and clozapine-N-oxide concentrations averaged 84% and 23% that of clozapine. Analyte concentrations were significantly correlated with daily dose. The method's ability to quantify clozapine and two major metabolites simultaneously with precision and sensitivity makes it useful in pharmacokinetic studies and therapeutic monitoring. PMID- 8353953 TI - Free thyroxine assessed with three assays in sera of patients with nonthyroidal illness and of subjects with abnormal concentrations of thyroxine-binding proteins. AB - Three methods for estimating free thyroxine (FT4) in serum were studied: equilibrium dialysis, the SPAC-ET FT4 radioimmunoassay kit, and the Amerlite MAB FT4 luminometric assay. Serum samples from 10 subjects with above-normal thyroxine-binding globulin (TBG), 6 with low TBG, 30 with familial dysalbuminemic hyperthyroxinemia (FDH), 13 with nonesterified fatty acids (NEFA) concentrations in serum > 1.0 mmol/L, and 178 patients with various degrees of nonthyroidal illness (NTI) were measured and compared with samples from 42 euthyroid blood donors. The Amerlite MAB FT4 assay compared well with equilibrium dialysis, whereas the SPAC-ET assay averaged 40% lower. All three assays were not influenced by changes in TBG and showed no or only little changes in the presence of NEFA. Mean FT4 values in the FDH samples were somewhat higher than in controls when measured with the SPAC-ET assay, about equal with equilibrium dialysis, and somewhat below the mean control value with the Amerlite MAB FT4 assay, although individual results were within the control reference range. In NTI patients, no FT4 values were below the control reference range by the Amerlite MAB FT4 assay, 4 of 178 were below this range by equilibrium dialysis, and 1 of 178 was below this range by the SPAC-ET assay. In all assays a large proportion of the NTI samples showed FT4 values above the control reference range, a result that will interfere with the efficacy of these assays for assessing thyroid function in NTI patients. PMID- 8353954 TI - Platelet-poor plasma serotonin in normal and preeclamptic pregnancy. AB - We determined serotonin concentrations in platelet-poor plasma (PPP) from 11 preeclamptic pregnant women and 11 normal pregnant women by HPLC with electrochemical detection after a concentration step. Serotonin concentrations in PPP are very low in comparison with those in platelets, so it is very important to avoid in vitro release of serotonin from platelets. We therefore investigated three types of anticoagulants, the method of blood sampling, and the influence of whether the first or second 10 mL of blood is assayed. The type of anticoagulant proved to be important, K3-EDTA giving the best results. The serotonin concentrations in PPP from the preeclamptic pregnant women were significantly higher (P = 0.0001) than in the normal pregnant women: mean values +/- SD were 27.0 +/- 13.5 and 2.8 +/- 1.4 nmol/L, respectively. We suggest that the measurement of serotonin in PPP might be helpful in study of the role of serotonin in the development of preeclampsia. PMID- 8353955 TI - Estimation of plasma and urinary hemoglobin by a rate spectrophotometric method. AB - A method is described for estimating plasma and urinary hemoglobin concentrations as low as 3 mg/L. The assay measures at 528 nm the rate of peroxidation of chlorpromazine by hemoglobin and is not affected by ascorbate and bilirubin concentrations up to 500 mumol/L. Results by this method (mean +/- SD: 54.4 +/- 41.6 mg/L; n = 19) correlated well with those by a scanning spectrophotometric method (52.5 +/- 41.6 mg/L; r = 0.96) and a Coulter Instrument method (r = 0.99; Coulter method: 125 +/- 15 g/L; rate method: 122 +/- 15 g/L; n = 10, r = 0.99). The correlation for assays of 20 plasma samples by our method and a tetramethylbenzidine method was also good (r = 0.95) though the latter gave lower results (31.1 +/- 31.6 mg/L) than the chlorpromazine method (50.9 +/- 41.1 mg/L). The chlorpromazine rate method gave an intra- and interday CV of 7.9% and 9.7%, respectively, at a hemoglobin concentration of 31 mg/L. PMID- 8353956 TI - Fast, manual, nonradioactive method for DNA sequencing. AB - We describe a protocol that allows nonradioactive detection of sequencing products after manual, direct, solid-phase sequencing of polymerase chain reaction-amplified DNA. The amplified DNA fragment to be studied is biotinylated at the 5' end of one of the two oligonucleotide primers used for amplification, allowing coupling to streptavidin-coated magnetic beads. The immobilized double stranded DNA is then separated into single strands by alkaline treatment. A 5' biotinylated sequencing primer is used after saturating with a biotin solution any possible remaining affinity sites on the streptavidin-coated magnetic beads. Sequencing is performed by using T7 DNA polymerase, and the sequencing products are electrophoresed in denaturing polyacrylamide sequencing gel. After transfer of the products to a nylon membrane, the sequencing pattern is revealed by chemiluminescence. Biotinylated alkaline phosphatase is bound to the 5' end of the sequencing primer via a streptavidin bridge and catalyzes the reaction by cleaving a phosphate group from a chemiluminescent substrate. The emitted photons are detected by exposing the membrane to x-ray film. This method is simple, rapid, and consistently successful and reproducible. PMID- 8353957 TI - Rapid multicomponent analysis of hemoglobin derivatives for controlled antidotal use of methemoglobin-forming agents in cyanide poisoning. AB - When cyanide poisoning is treated with a methemoglobin-forming agent, oxidative metabolism is protected at the expense of the oxygen capacity of the blood. The affinity of methemoglobin for CN- is high enough to compete with cytochrome oxidase, which protects the latter from becoming blocked, but all hemoglobin used for this purpose is lost for the transport of oxygen. Therefore, the fractions of the various hemoglobin derivatives present in the blood should be carefully monitored during this kind of treatment. After we had developed a multiwavelength spectrophotometric method for this purpose, we studied the feasibility of using a modified commercial six-wavelength hemoglobin photometer (Radiometer OSM3) for easy and rapid analysis of methemoglobin and methemoglobin cyanide in small samples of blood. All conditions appeared to be fulfilled for the construction of a practical multiwavelength photometer for reliably monitoring methemoglobin therapy in patients with cyanide poisoning, even in the presence of carboxyhemoglobin, as often occurs in fire victims. PMID- 8353958 TI - A method to quantify deviations from assay linearity. AB - We present a statistical method to quantify deviations from linearity for assays that veer from linear assay responses. Our procedure handles the common case of unequally spaced analyte levels and nonconstant variance and provides a least squares estimate with a confidence interval for the amount of deviation from assay linearity at a specified analyte concentration. This estimate of assay bias due to nonlinearity goes beyond the NCCLS EP6 lack-of-fit test, which tests for only the presence of nonlinearity. Knowing that nonlinearity is present is insufficient; users need to know the magnitude of the bias caused by nonlinearity. Our method can also be used with multifactor designs that estimate other systematic assay effects such as drift and carryover, thus obviating the need for a separate protocol to assess linearity. The procedure is carried out by adding extra columns to the design matrix corresponding to the concentration level(s) of interest. The extra columns, which replace the quadratic column, are orthogonal to all other columns. We describe a general method of constructing the new columns, and illustrate the procedure with a manual ammonia assay example dataset from EP6. PMID- 8353959 TI - Measurement of carboxyhemoglobin and total hemoglobin by five specialized spectrophotometers (CO-oximeters) in comparison with reference methods. AB - We measured total hemoglobin (CtHb) and carboxyhemoglobin (COHb) in 100 patients' blood samples by using five specialized spectrophotometers (CO-oximeters)--IL 482 CO-Oximeter, Corning 2500 CO-oximeter, Radiometer OSM 3 Hemoximeter, Corning 270 CO-oximeter, and the AVL 912 CO-Oxylite--and compared the results with those obtained with the manual cyanmethemoglobin method and a gas-chromatographic (GC) method, respectively. For the CtHb measurements, the differences between the cyanmethemoglobin method and the CO-oximeters were not clinically important for any model. For the blood COHb measurements, the direction of the bias relative to GC was dependent on COHb concentration. In general, the CO-oximeters underestimated COHb concentration for COHb > 2.5% of total hemoglobin but overestimated COHb concentration for COHb < or = 2.5%. We conclude that all five CO-oximeters compared favorably with the reference methods for CtHb and for high concentrations of COHb. However, the inaccuracy of CO-oximeters for low concentration (< or = 2.5%) COHb measurements may make these instruments unsuitable for some applications. PMID- 8353960 TI - Latex agglutination test for detecting antibodies to Treponema pallidum. AB - We have developed an automated latex agglutination test for Treponema pallidum (TPLA) for measurement of the concentration of treponemal antibodies in syphilitic sera. The assay needs neither a complicated pretreatment of the sera nor special techniques. Intra- and interassay precision studies showed high reproducibility. Potentially interfering substances, such as bilirubin, hemoglobin, triglycerides, and rheumatoid factor, did not affect the results. The results obtained with the TPLA test showed a strong correlation with those from conventional methods. This test for antibodies to T. pallidum may be useful for the mass screening of syphilitic infections. PMID- 8353961 TI - Evaluation of evacuated blood-collection tubes: effects of three types of polymeric separators on therapeutic drug-monitoring specimens. AB - The potential of three types of separator materials found in conventional blood collection tubes for interference in therapeutic drug measurements was assessed. None of the separators (based on acrylic, silicone, or polyester polymers) had any significant effect on the concentrations of seven drugs (theophylline, digoxin, phenytoin, phenobarbital, gentamicin, ethanol, and cyclosporine) in blood specimens that were processed and analyzed promptly. Storage of specimens for 24 h resulted in an average 2.4% increase in theophylline values in specimens collected in tubes with the acrylic separator (P = 0.024); an average 8.1% decrease in phenytoin in specimens collected in tubes with the polyester-based separator (P < 0.001); and an average 4.2% decrease in phenobarbital in specimens collected in tubes with the polyester-based separator (P = 0.02). All other drug concentrations were not significantly affected. A small decrease in phenytoin (7.9%; P < 0.01) was seen when the specimen volume in 7-mL tubes containing polyester-based separator was reduced to 1.0 mL; all other drug concentrations were unaffected by partial filling of tubes. Paired blood specimens from pediatric patients, when collected in plain tubes and tubes containing acrylic separator, yielded no significant differences for theophylline, digoxin, tobramycin, phenytoin, or phenobarbital concentrations. The three commercially available separators had only small effects on therapeutic drug concentrations, and a newly developed separator based on an acrylic resin was suitably inert. PMID- 8353962 TI - Within- and between-subject biological variations of follitropin, lutropin, testosterone, and sex-hormone-binding globulin in men. AB - The within-subject and between-subject biological variation of the serum concentrations of follitropin, lutropin, sex-hormone-binding globulin, and testosterone; the ratio between the serum concentrations of testosterone and sex hormone-binding globulin; and the concentration of testosterone in saliva have been studied in a group of 20 men during 12 months. The between-subject coefficients of variation (CVs) were 36.0% for follitropin, 37.0% for lutropin, 42.7% for sex-hormone-binding globulin, 21.3% for testosterone in serum, 28.8% for testosterone in saliva, and 51.6% for the ratio between serum concentrations of testosterone and sex-hormone-binding globulin. The medians of the within subject CVs for the respective analyses and ratio were 17.3%, 24.0%, 12.1%, 10.9%, 17.3%, and 9.4%. These data were used to calculate the desirable imprecision, the critical difference for significant change detection, and the index of individuality. PMID- 8353963 TI - Early diagnosis of acute myocardial infarction with use of a rapid immunochemical assay of creatine kinase MB isoenzyme. AB - In 195 patients presenting with chest pain and referred acutely for cardiological assessment, blood was taken immediately for assay of creatine kinase (CK; EC 2.7.3.2) MB isoenzyme by an immunochemical method and results [mass units of enzyme per liter of plasma (microgram/L)] were obtained within 30 min of sampling. Diagnosis of acute myocardial infarction in the patients was made independently, based on electrocardiograms and conventional cardiac enzyme profiles. The administration of any thrombolytic therapy in response to the CK-MB concentration result was also noted, allowing assessment of the assay's potential influence on patient management in addition to the diagnostic efficiency evaluation. The study demonstrated that, when blood samples were collected on admission to hospital and the decision level suggested by the manufacturers was utilized, the assay had an immediate sensitivity of 52% and a specificity of 97%. Of the 81 patients who were shown by conventional means to have had acute myocardial infarction, 8 (10%) had equivocal electrocardiograms but positive CK MB concentration results. In four of these patients (5%), thrombolytic therapy was given on the basis of the clinical features and a positive CK-MB concentration result alone. PMID- 8353964 TI - Primary aldosteronism in a patient with an aldosterone-producing adenoma. AB - We describe an unusual patient presenting with a history of refractory hypertension and hypokalemia. Initial screening tests for adrenal hypertension were consistent with primary aldosteronism and an abdominal computed tomography scan showed an 8-mm left adrenal mass. However, adrenal venous sampling revealed markedly suppressed plasma aldosterone in the left adrenal vein but increased plasma aldosterone in the right adrenal vein. Therefore, on the basis of the clinical, radiographic, and laboratory findings, we concluded that the patient had a nonfunctioning adrenocortical adenoma on the left and an aldosterone producing adrenocortical adenoma on the right, with the aldosteronoma resulting in hypertension and hypokalemia. Right adrenalectomy decreased the hypertension and corrected the hypokalemia. The right adrenal contained a 7-mm nodule microscopically consistent with the diagnosis of a cortical adenoma. The case highlights key steps and potential pitfalls in the evaluation of adrenal hypertension. PMID- 8353965 TI - Interference of polyclonal free light chains with identification of Bence Jones proteins. AB - We present a case in which kappa free light chains caused difficulty in interpreting classical urinary immunoelectrophoresis, but immunofixation electrophoresis (IFE) demonstrated the presence of a lambda-Bence Jones protein. Analysis of the urine by Ouchterlony double diffusion and IFE after gel filtration chromatography showed that the difficulty was caused by the presence of large amounts of polyclonal free light chains. The workup also demonstrated that although IFE is the more sensitive and specific technique, IFE performed on concentrated urinary samples is especially subject to misinterpretation unless densely staining patterns are diluted and reassayed. This process of sample dilution provides a means for titrating antigen and antibody concentrations such that condition-specific patterns become visible on the gel. This workup also shows that, at some dilutions, polyclonal free light chains may migrate in the same manner as an oligoclonal band in a so-called ladder configuration. These bands were observed from both monomeric and dimeric fractions isolated by gel chromatography, consistent with reports that this pattern is largely linked to the isoelectric points of the molecules. We speculate that, in rare instances, the distinction between polyclonal and monoclonal kappa free light chains migrating as a ladder-banding pattern may be equivocal. PMID- 8353966 TI - Factitious hyperthyroxinemia due to a monoclonal IgA in a case of multiple myeloma. AB - A clinically euthyroid 53-year-old woman with an IgA-lambda-secreting multiple myeloma presented with increased serum concentrations of thyroid hormones. Laboratory studies revealed increased total thyroxine (T4) and triiodothyronine (T3) concentrations, a high-normal free T4 concentration, and a normal basal thyrotropin (TSH) concentration with a normal response to thyroliberin (TRH). Her serum concentration of IgA was 11,040 mg/L (normal range 900-4500 mg/L) and immunoelectrophoresis revealed it to be monoclonal. This monoclonal IgA bound both T4 and T3, as determined by serum immunoelectrophoresis and direct binding studies. Immunoelectrophoresis in the presence of [125I]T4 or [125I]T3 localized the radiolabeled iodothyronines to a band corresponding exactly to the precipitin arc of the monoclonal IgA. We performed direct binding studies with IgA purified by affinity chromatography with the lectin jacalin. Purified IgA (50 micrograms) bound both [125I]T4 (12.3%) and [125I]T3 (2.7%) specifically and in a dose dependent manner. Scatchard analysis of competitive-binding data utilizing [125I]T4 and unlabeled T4 revealed a Kd of 2.2 x 10(-7) mol/L. The binding capacity for T4 was approximately 7 mumol/L. Thus, in this case of IgA-secreting myeloma, the monoclonal IgA acts as an additional thyroid hormone-binding protein in serum that interferes in the T4 and T3 RIAs. This is the first report of a monoclonal IgA producing an apparent euthyroid hyperthyroxinemia. PMID- 8353967 TI - Stability of vitamin A circulating complex in spots of dried serum samples absorbed onto filter paper. PMID- 8353968 TI - Radioimmunoassay for a new bone resorption marker and results for pediatric subjects. PMID- 8353969 TI - Low-density lipoprotein particle size in familial hypercholesterolemia. PMID- 8353970 TI - Improved correlation of sweat chloride quantification by the CF Indicator System and the Gibson-Cooke Sweat Test. PMID- 8353971 TI - Free thyroxine measured by the Ciba Corning ACS-180 on samples from patients with familial dysalbuminemic hyperthyroxinemia. PMID- 8353972 TI - Fluoxetine, an antidepressant, and norfluoxetine, its metabolite, determined by HPLC with a C8 column and ultraviolet detection. PMID- 8353973 TI - Immunobilization of barley oxalate oxidase onto alkylamine glass for determining urinary oxalate. PMID- 8353974 TI - Cysteine proteinase activity in synovial fluids measured with a centrifugal analyzer. PMID- 8353975 TI - Xylose, anti-gliadin, and anti-endomysium antibodies in adult celiac disease. PMID- 8353976 TI - Ethylene glycol, glycolic acid, and metabolic acidosis of unknown origin. PMID- 8353977 TI - Choice of anticoagulant affects measurement of plasma fibrinogen. PMID- 8353978 TI - Lipid factors as predictors of coronary disease. PMID- 8353979 TI - Lack of immunosuppressive effect of low-dose oral methotrexate on lymphocytes in rheumatoid arthritis. AB - Whether methotrexate (MTX) is effective in rheumatoid arthritis (RA) because of immunosuppressive and/or anti-inflammatory mechanisms of action is controversial. Many lines of investigation point to the latter. We evaluated DNA synthesis in peripheral blood lymphocytes (PBL) from 33 RA patients on oral MTX (7.5-15 mg/wk) and in 30 healthy controls by flow cytometric cell cycle analysis (CCA). DNA synthesis was also evaluated with a thymidilate synthetase activity assay (TSA) (3H-deoxyuridine incorporation) in 12 patients and 21 controls (12 on MTX and NSAID, and 9 healthy subjects). The patients had taken MTX for at least 3 months and were in different stages of clinical activity. There were no significant differences in TSA or in the cell cycle phase distributions (especially the S phase) between treated RA patients and controls. These data suggest that low-dose oral MTX does not inhibit DNA synthesis and therefore does not have an immunosuppressive effect on lymphocytes from patients with RA. PMID- 8353980 TI - Selective suppression of resting B cell function in patients with systemic lupus erythematosus treated with cyclophosphamide. AB - The immunological function of patients with inactive systemic lupus erythematosus (SLE) receiving chronically administered, low-dose cyclophosphamide (CY) together with prednisolone (PSL) was compared with that of inactive patients receiving PSL alone. A striking selective suppression of "genuine" resting, but not "partially" or "fully" activated, B cell function was noted in the patients receiving PSL + CY as measured by Staphylococcus aureus Cowan I (SAC)-induced proliferative responses by Percoll-separated small resting B cells of high density; the small resting B cells sedimenting in a high density fraction were more responsive to SAC in patients treated with PSL alone than those in normal controls. However, the spontaneous proliferation and spontaneous secretion of immunoglobulins by peripheral blood B cells were elevated in both the patient groups. The proliferative responses to phytohaemagglutinin and concanavalin A by T cells were not significantly different between both patient groups. The data indicate that the genuine resting B cells may be the major target for the CY effect in SLE, and thus such selective suppression may help explain the efficacy of CY and PSL together in treating SLE. PMID- 8353981 TI - Copper and zinc status in rheumatoid arthritis: studies of plasma, erythrocytes, and urine, and their relationship to disease activity markers and pharmacological treatment. AB - We studied the status of copper and zinc in rheumatoid arthritis (RA). The aims of the work were to ascertain whether or not RA is associated with copper and/or zinc deficiency, to establish the relationship between these trace metals and the main biohumoral and clinical indices of the disease, and to examine the effect on copper and zinc of the drugs normally used by RA patients. Metal levels were measured by atomic absorption spectroscopy in the plasma, whole blood cells and 24 hr urine of 120 RA patients; 70 patients suffering from primary osteoarthritis were used as the control group. In the plasma of RA patients copper and ceruloplasmin levels were found to be significantly increased whereas zinc levels were significantly decreased. No major variations were observed in the blood cell and 24 hr urine copper and zinc levels. Plasma copper was significantly correlated with some of the biohumoral markers of RA, but did not correlate with any of the clinical indices of the disease. Plasma zinc was significantly correlated with numerous of the biohumoral as well as clinical markers of RA. With the exception of an increased urinary excretion of copper in D-penicillamine treated RA patients, drug therapy did not influence the copper status in RA. Conversely, plasma zinc was found to be lower in RA patients taking NSAIDs and/or steroids. These results suggest the following conclusions: i) RA patients do not seem to be deficient in either copper or zinc; ii) plasma copper appears to be a poor index of RA severity; iii) plasma zinc could have some practical value in defining the overall severity of the disease. PMID- 8353982 TI - Intravenous and oral cyclophosphamide pulse therapy in rheumatic diseases: side effects and complications. AB - Twenty five patients (12 with systemic lupus erythematosus, 6 with Wegener's granulomatosis, and 7 with miscellaneous rheumatic diseases) who had been on intravenous or oral cyclophosphamide pulse therapy for more than 3 months were evaluated for safety of treatment. Side effects were reported by 20 patients (80%), mainly nausea (17 patients, 68%). Complications were observed in 13 patients (52%), of whom 6 had severe infections (24%). Oral cyclophosphamide given in repeated low dose pulses (5 mg/kg for 3 consecutive days) is better tolerated with regard to nausea than intravenous administration. The use of cyclophosphamide therapy is recommended in patients with disease that does not respond to conventional regimens, although the attending physician should be aware that infections may appear at any time during treatment, and effective prophylaxis against nausea is required. PMID- 8353983 TI - Multicenter study of the safety/efficacy of misoprostol in the prevention and treatment of NSAID-induced gastroduodenal lesions. AB - Gastrointestinal symptoms and lesions are often associated with the clinical use of non-steroidal antiinflammatory drugs (NSAIDs). An open-label, single arm multicenter Italian study evaluated if misoprostol, a prostaglandin E1 analogue with gastroduodenal mucosal protective activity, was effective in the prevention and treatment of NSAID-induced gastroduodenal lesions. Patients affected by rheumatoid arthritis (RA) or osteoarthritis (OA), in treatment with NSAIDs and suffering from gastric symptoms or gastroduodenal lesions related to NSAID use, were admitted to the study. Gastrointestinal and arthritic symptoms were assessed before and after 4 weeks co-administration of an NSAID (the most frequent was diclofenac, used in 35% of the RA and in 22% of the OA patients, followed by piroxicam and tenoxicam respectively) + misoprostol (200 mcg two times daily in 58% of the cases, 200 mcg three times daily in 39%, 200 mcg four times daily in 3%). On admission and after 4 weeks of therapy a gastrointestinal endoscopy was performed to evaluate the condition of the gastroduodenal mucosa. Final results showed that: (i) NSAID-related gastric lesions were more frequent than duodenal lesions; (ii) when patients were given misoprostol and NSAIDs, 96% of them did not develop gastric lesions and 97% did not develop duodenal lesions; (iii) even when NSAID therapy was continued, gastric or duodenal lesions induced by NSAIDs healed or in any case did not worsen in 92% and 91% respectively of the cases; (iv) during the period of coadministration of NSAIDs+misoprostol, NSAID-related UGI symptoms disappeared or improved in 77% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8353984 TI - Functional characterization of T cells bearing the gamma/delta T-cell receptor in patients with primary Sjogren's syndrome. AB - High percentages of gamma/delta+ T cells in the peripheral blood of a subgroup of patients with primary Sjogren's syndrome (SS) were found. This allowed us to purify and analyze them without their being previously expanded in vitro, and to investigate, therefore, the role of these cells in the pathological immune response which characterizes such systemic autoimmune disorders. The results showed poor proliferation of patient gamma/delta+ T cells in response to anti CD3, due not to macrophage-dependent suppression but to defective interleukin 2 (IL-2) synthesis. Despite the defective proliferation patient gamma/delta+ cells, unlike those of the normal controls, provided a helper effect in inducing B cells to secrete immunoglobulins (Ig), particularly when they were preincubated with IL 2. The relative increase in a gamma/delta+ T cell subset which, although it secretes low levels of IL-2, is able to provide help for B-cell Ig synthesis, suggests that this T-cell subpopulation may be functional in vivo and may be involved in the pathological immune response encountered in pSS. PMID- 8353985 TI - Effect of antimicrobial treatment on chronic reactive arthritis. AB - In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated. At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group. We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established. PMID- 8353986 TI - Increased prevalence of antibodies to adenovirus and respiratory syncytial virus in polymyalgia rheumatica. AB - Serum antibodies to a panel of 13 viruses and to Mycoplasma pneumoniae and Chlamydia psittaci were tested in 17 patients with polymyalgia rheumatica (PMR) and in 17 age- and sex-matched controls with osteoarthritis seen in the same rheumatological clinic. Antibodies to adenovirus (ADV) and respiratory syncytial virus (RSV) were significantly more prevalent in PMR. These antibodies were titred in 26 patients with PMR, including those evaluated in the pilot study (17 women, 9 men, mean age 72.5 years), and in 26 controls. 25/26 PMR patients tested positive for antibodies to ADV vs. 12/26 controls (p = 0.0002) and the concentration was higher in patients than in controls (p < 0.01). Antibodies to RSV were present in all PMR patients and in 12/26 controls (p = 0.00005) and their concentration was higher in patients than in controls (p < 0.01). Serial determinations performed in 18 PMR patients showed that the antibody titer did not change significantly. These data suggest that a trivial infection may trigger PMR in elderly people, with ADV and RSV among the possible microorganisms involved. PMID- 8353987 TI - Geographic distribution of calcium pyrophosphate (CPPD) deposition disease in pre Columbian North America: independent validation of CPPD criteria. AB - Calcium pyrophosphate deposition disease (CPPD), a form of crystalline arthritis, has a unique distribution in the Early to Middle Archaic Periods (3000 to 8000 years before the present) of North America, contrasting with the generalized geographic distribution of osteoarthritis. Incursion of CPPD into specific regions suggests possible migration patterns. The disparate geographic distribution of CPPD and osteoarthritis provide independent verification of the validity of diagnostic criteria utilized for the identification of CPPD. PMID- 8353988 TI - Nerve growth factor and mast cell distribution in the skin of patients with systemic sclerosis. AB - Nerve growth factor (NGF), a well-characterized neurotrophic factor, induces an increase in the number of mast cells (MCs) in the peripheral tissues of developing rats, as well as histamine release in fully differentiated MCs. Since MCs increase in the dermis of patients with early systemic sclerosis (SSc), we examined the distribution of NGF in the skin of patients affected by SSc. Immunohistochemical studies showed that NGF distribution was more intense in the dermis of patients with SSc than in the skin of controls. A possible correlation between MCs and NGF in disease activity is hypothesized. PMID- 8353989 TI - Lupus psychosis: differentiation from the steroid-induced state. AB - Steroid induced psychosis in SLE is rare but clinically important, and often difficult to distinguish from lupus cerebritis. We report a patient with SLE who became depressed following an increase in her steroid dosage. Based on her clinical presentation and high levels of antibodies to P ribosomal proteins (both in CSF and serum) a diagnosis of lupus cerebritis was made. Steroid dosage, time intervals, and the duration of mental changes may help in differentiating steroid psychosis from lupus cerebritis. No single laboratory test sufficient to establish a definitive diagnosis of lupus cerebritis is available at the present time. However, elevated levels of antibodies to P ribosomal proteins may assist in confirming the diagnosis of this condition. PMID- 8353990 TI - Expansion of gut associated immunoglobulin A secreting lymphocytes in rheumatoid arthritis correlates with high levels of serum IgA. AB - We report the emergence of polyclonal expansion of gut lymphocyte associated tissues producing IgA in a patient with rheumatoid arthritis associated with a high serum IgA concentration. The role of IgA in rheumatoid arthritis is reviewed. PMID- 8353991 TI - Normal levels of soluble CD4 in sera from patients with juvenile chronic arthritis. AB - Sera from a group of patients with juvenile chronic arthritis (JCA) were tested for soluble CD4 (sCD4). In most cases normal levels of the molecule were detected independent of disease activity. Similar results were obtained when sera from a population of adult rheumatoid arthritis (RA) patients were analyzed. Immunophenotypic studies of circulating mononuclear cells from seven JCA patients with active disease showed that T cells did not express activation markers. Finally, preliminary experiments showed that sCD4 levels were high in the synovial fluids from 3 RA patients as compared with paired serum determinations. PMID- 8353992 TI - Coexistence of human immunodeficiency virus type 2 (HIV2) and rheumatoid arthritis. PMID- 8353993 TI - Methotrexate in juvenile chronic arthritis. PMID- 8353994 TI - Red blood cell and platelet autoantibodies in scleroderma. PMID- 8353995 TI - Comparison of a fluorometric test with the standard ELISA assay for the detection of anticardiolipin antibodies. PMID- 8353996 TI - Cryoglobulinemia related to hepatitis C virus infection in patients with human immunodeficiency virus infection. PMID- 8353997 TI - Raised IgA kappa/lambda ratio in juvenile chronic arthritis. PMID- 8353998 TI - Erythrocyte binding of antiphospholipid antibodies. PMID- 8353999 TI - T cell-targeted immunotherapy in murine collagen-induced arthritis. AB - Counteracting the effect of autoimmunity can be achieved by elimination or inactivation of autoreactive T cells. We have focused on two approaches targeting on autoaggressive T cells in the model of collagen-induced arthritis (CIA) in mice. First, type II collagen (CII) primed DBA/1 mice were treated with various monoclonal antibodies (mAb) specific for the beta chains of the T cell receptor (TCR) using a protocol resulting in a long-term elimination of the target T cells. Indeed, CIA could be suppressed by injection of anti-V beta 8.1, 2 mAb and down-regulated by that of anti-V beta 2 and/or anti-V beta 5, presumably by deleting pathogenic T cell clones. In contrast, treatment with either anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Second, we generated CII-specific T cell hybrid clones that recognize the antigenic peptides in association with Kq and IA(q) molecules respectively for CD8+ and CD4+ cells. Vaccination with the irradiated hybrid clones, 3 weeks prior to immunization, was effective in preventing the development of arthritis. Furthermore, this suppression was antigen and disease specific. Most importantly, one CD8+ clone could reverse the ongoing disease. These new therapeutic approaches derived from animal models may offer a hope of more selective interventions for the treatment of human autoimmune diseases. PMID- 8354000 TI - Systemic vasculitis. AB - The systemic vasculitides are comparatively rare but important disorders of childhood. Apart from Henoch-Schonlein purpura, which is the commonest example in paediatric practice, Kawasaki disease is most often encountered. Polyarteritis and Wagener's granulomatosis have a lower incidence but are associated with a high morbidity and mortality. Newer investigative procedures and therapeutic approaches have led to more accurate diagnoses and improved outcome but further advances await a better understanding of the vasculitides: polyarteritis; Kawasaki disease; Wagener's granulomatosis; and ANCA in childhood. PMID- 8354001 TI - Leukocyte adhesion. AB - Adhesion of leukocytes is a major event in the induction and effector phases of the immune response, as well as in inflammatory reactions. T-cell activation requires interaction with antigen-presenting cells (APC), B-cell activation needs cognate interaction with T-cells, while cytotoxic T cells strongly bind target cells. Migration of leukocytes into inflammatory areas is mediated by a crucial step of leukocyte binding to endothelial cells followed by trans-endothelial migration. Adhesion molecules mediating these various cell to cell interactions belong to three families, i.e. the immunoglobulin superfamily, integrins and selectins. PMID- 8354002 TI - Heat-shock proteins and juvenile chronic arthritis. AB - Heat-shock proteins are a category of proteins that are synthesized under stressful conditions (such as increased temperatures) both by prokaryotic and eukaryotic cells. Heat-shock proteins are a major target of the immune response and thus can be considered dominant antigens. Under physiological circumstances the response to heat-shock proteins is considered to play a role in the overall defence against bacterial infections. An aberrant immune response against heat shock proteins may lead to autoimmunity, as illustrated by adjuvant arthritis in Lewis rats. Current evidence also points towards a role of T cell immunity against heat-shock proteins in the development of human autoimmune diseases such as juvenile chronic arthritis. PMID- 8354003 TI - Signal transduction by inflammatory cytokines. AB - The mechanisms by which the inflammatory cytokines interleukin-1 and interleukin 6, and tumour necrosis factor alpha activate cellular genes are reviewed. Common usage of some receptors and transcription factors are beginning to emerge, and many offer insights into newer therapeutic options. PMID- 8354004 TI - Can we prevent long term cardiac damage in Kawasaki disease? Lessons from Lactobacillus casei cell wall-induced arteritis in mice. AB - A single intraperitoneal injection of sonicated cell walls from group B Lactobacillus casei (LC) produces an acute inflammatory coronary arteritis in mice that closely resembles the coronary arteritis found in children with Kawasaki Disease (KD). The coronary arteritis is accompanied in its early stages by pancarditis and valvulitis, and in its later stages by coronary artery aneurysms, stenoses, and myocardial infarctions. The importance of this model is two-fold. First, it provides the opportunity to study the natural history of coronary artery disease over a relatively short life span. Second, it provides a model system in which the effects of immunological and pharmacological interventions may be tested without putting human life at risk. Studies to date indicate that inflammatory coronary arteritis such as occurs in this model and in children with KD is associated with the accelerated development of coronary artery insufficiency and premature death from cardiovascular disease. The use of immunomodulators or other agents early in the disease course to reduce the frequency and severity of the coronary arteritis appears to reduce the incidence of premature death in this mouse model and may reduce the consequences of KD as well. PMID- 8354005 TI - Intravenous immunoglobulin (IVIg) in the treatment of autoimmune and inflammatory diseases. AB - The beneficial effect of intravenous immunoglobulin (IVIg) in certain autoimmune disorders has led to the development of clinical trials in a large number of autoimmune and systemic inflammatory diseases. Experimental studies are being carried out to understand better the mechanisms of action of IVIg. In this review, we discuss the clinical use of IVIg in autoimmune disorders and outline the possible mechanisms by which IVIg may be exerting an immunoregulatory effect in various autoimmune and systemic inflammatory diseases. A clear understanding of the mechanisms of action of IVIg in autoimmune diseases will facilitate the optimization of their use as a therapeutic alternative to conventional immunosuppression. PMID- 8354006 TI - Immunogenetic aspects of juvenile chronic arthritis. AB - The HLA associations of Juvenile Chronic Arthritis are reviewed in the light of the newest results. The most convincing data are available about the early onset pauciarticular Juvenile Chronic Arthritis (EOPA-JCA), where there are highly significant associations with 3 different regions of the HLA system: the HLA-A locus (HLA-A2), the HLA-DR/DQ region (HLA-DR5 and DR8 haplotypes) and the DP region (DPB1*0201). All these associations are independent of each other and not brought about by linkage disequilibrium. There are significant interactions between the associated alleles DPB1*0201 and DR5 haplotypes, DPB1*0201 and DR8 haplotypes as well as between A2 and DR5 and DR8 haplotypes, and between A2 and DPB1*0201. The association with the DR/DQ haplotypes reveal that most likely the DQA1 gene locus is primarily associated with JCA. There is a common motif which is present on all susceptible DQA1 alleles (0401, 0501, 0601) and not present on all the others (12). Taking all these information together, the following hypothesis is proposed: the observed HLA associations are a reflection of the direct involvement of the HLA genes in pathogenesis. The normal function of HLA molecules, namely the presentation of peptides of the T-cell receptor, is assumed to be a key mechanism in pathogenesis where an arthritogenic peptide is specifically bound by the DQ molecules, with binding specificity determined by the common motive on the DQA chain. It is possible that some of the arthritogenic peptides may be derived from self-histocompatibility antigens such as HLA-A2 and/or DPB1*0201. PMID- 8354007 TI - T cell receptor variable region gene usage in juvenile chronic arthritis. AB - Up to now the data regarding T cell receptor V-gene usage by juvenile chronic arthritis synovial T lymphocytes has been conflicting. Thus, some studies claim that locally in the diseased joint there is an oligoclonal expansion of T cells with restricted T cell receptor variable region gene usage while others have found V-gene usage in the joint compatible with a polyclonal expansion of the T cells. PMID- 8354008 TI - Total hip replacement for juvenile chronic arthritis. PMID- 8354009 TI - Imaging in pediatric rheumatology. PMID- 8354010 TI - Ocular involvement during chronic inflammatory diseases in children. PMID- 8354011 TI - Relevance of the pharmacokinetics of non-steroidal anti-inflammatory drugs (NSAIDs) in children. AB - The pharmacokinetics of the NSAIDs is relevant to therapy in different ways: absorption, protein binding and distribution, metabolism and elimination. The pharmacokinetics of a drug is most relevant to therapy when plasma concentrations of the drug are related to efficacy and/or to side effects. The kinetic parameters then allow one to calculate the optimal dose regimen, i.e. the one maintaining plasma concentrations within the therapeutic range. The pharmacokinetic characteristics of the different NSAIDs relevant to therapy in children are reviewed. PMID- 8354012 TI - Pain in juvenile chronic arthritis: consequences for the musculo-skeletal system. AB - Pain in juvenile chronic arthritis is underestimated. Children often don't verbalize their pain adequately. On a pain scale they usually grade pain lower than adults. Pain perception always depends on subjective factors, especially the child's stage of development. The younger the child the more nonverbal pain expressions dominate. Malpositioning of involved joints or abnormal patterns of movement are often the only signs of pain. This is demonstrated in an inquiry directed to the parents of 111 small children with different subgroups of juvenile chronic arthritis. In a reflex reaction children bring their inflamed joints into a pain relieving position. This triggers a vicious circle which may result in joint deformity and permanent handicap. Arthritis interferes with the child's activities. Behavioural changes and finally developmental disturbances can follow. PMID- 8354013 TI - Is there a useful model for the study of childhood uveitis and arthritis? PMID- 8354014 TI - Naturally occurring arthritis in experimental animals. PMID- 8354015 TI - Dose response evaluation. Use of plasma concentration confidence intervals as a tool to predict optimal drug dose ratio. PMID- 8354018 TI - Nonparametric meta-analysis of published data on kidney-function dependence of pharmacokinetic parameters for the aminoglycoside netilmicin. AB - The distribution and elimination of various drugs depend on kidney function. This dependence is published either as a linear regression equation or as the discrete extreme values for normal kidney function and anuria. A meta-analysis of the published pharmacokinetic data is required to build up a knowledge-based computer system for dosage adjustment in renal failure. A sample comparison of 4 statistical methods for meta-analysis was performed by applying them to 13 publications about the aminoglycoside netilmicin. Parametric meta-analytical methods I and II are based on regression equations alone (Z-transformation, maximum likelihood) and yield unreliable data, especially with regard to extreme values for anuria. The parametric meta-analytical method III is based on means of extreme values (standard 2-stage approach) and does not permit a decision as to whether linear interpolation of a parameter (e.g. volume of distribution) can be used for all degrees of renal insufficiency. In contrast, the nonparametric median (meta-analytical method IV) is based on the extreme values calculated from regression equations and empirical extreme values combined into 1 group of data on normal kidney function and another on anuria. For netilmicin, the meta analytical median with the 95% confidence interval (95% CI) yields a significant increase in the dominant elimination half-life from 2h (95% CI 1.9h, 2.6h) in patients with normal kidney function to 45h (95% CI 41h, 301h) in those with anuria (p = 0.001). For a normal bodyweight of 65kg, the volume of distribution also increases significantly from 13L (95% CI 9L, 15L) to 20L (95% CI 14L, 21L) in patients with anuria (p = 0.04). Thus, drug dosage adjustment according to therapeutic peak and trough concentrations requires knowledge of the distribution and elimination parameters, since they can both be independently altered in renal failure. We conclude that the most robust meta-analysis of these alterations is achieved with the nonparametric median of extreme values. PMID- 8354017 TI - Pharmacokinetic optimisation of general anaesthesia in pregnancy. AB - A significant proportion of women require general anaesthesia during pregnancy or for delivery. There are many practical difficulties in studying anaesthetic drugs and techniques to determine what may be best for both the mother and fetus. Physiological changes of pregnancy may alter the pharmacokinetics and pharmacodynamics of anaesthetics and the fetal disposition of drugs is largely unknown. With the limited pharmacokinetic data available, conclusions on the suitability of drugs are reached in conjunction with sophisticated neonatal neurobehavioural testing. The normal fetus appears able to withstand a variety of anaesthetic techniques but there is little information regarding the compromised fetus or premature neonate. Provided that adequate maternal anaesthesia is achieved, it is prudent to choose an anaesthetic technique which minimises fetal exposure to drugs and use agents which can be eliminated quickly by the neonate. Currently available drugs with rapid maternal and neonatal elimination include propofol, suxamethonium, atracurium, nitrous oxide and isoflurane. PMID- 8354019 TI - Effect of continuous arteriovenous haemofiltration on pharmacokinetics of amrinone. AB - This case report details the pharmacokinetic adjustments of an amrinone infusion in a paediatric patient who developed multiorgan system failure with anuric renal failure and was prescribed continuous arteriovenous haemofiltration. A significant proportion of clearance of amrinone is nonrenal. Near normal amrinone clearance can occur in patients with hepatic and renal dysfunction if continuous arteriovenous haemofiltration is used. Hepatic dysfunction with renal failure may require a reduction in the continuous amrinone infusion rate as previously reported for neonates. PMID- 8354020 TI - Clinical pharmacologists and health care reform: contributing to the debate. PMID- 8354016 TI - Pharmacokinetic drug interactions with ACE inhibitors. AB - Angiotensin converting enzyme (ACE) inhibitors which have active moieties excreted mainly in urine require adjustment of either the dose or the interval between doses in patients with moderate to severe renal dysfunction or severe congestive heart failure. Those agents such as temocapril (CS 622) and fosinopril, excreted both in urine and bile, may not require such adjustment. Renal clearance of ACE inhibitors may be reduced and some accumulation may occur in elderly patients with mild renal dysfunction or congestive heart failure. The bioavailability of ACE inhibitors is reduced by concomitant food or antacids which may slow gastric emptying and raise gastric pH. Pharmacokinetic interactions with ACE inhibitors are unlikely in patients receiving thiazide or loop diuretics. When ACE inhibitors are given hyperkalaemia may occur in patients with renal insufficiency, those taking potassium supplements or potassium-sparing diuretics, and in diabetic patients with mild renal impairment. While no pharmacokinetic interaction precludes use of this combination, the pharmacokinetics of some ACE inhibitors are subject to greater variability when patients also receive beta-blockers. Calcium antagonists and ACE inhibitors have additive anti-hypertensive effects and pharmacokinetic interactions between these agents are unlikely. One report exists of a significant effect of coadministered hydralazine on the pharmacokinetics and urinary excretion of lisinopril. Data on interactions between ACE inhibitors and digitalis are contradictory. There is no evidence that the concomitant use of ACE inhibitors and digoxin is associated with an increased risk of digitalis toxicity. ACE inhibitors are mainly excreted by glomerular filtration and renal tubular secretion. Possible interactions between ACE inhibitors and probenecid have been noted, with renal and total body clearance of ACE inhibitors being potentially reduced in the presence of probenecid. Probenecid pretreatment may enhance the pharmacodynamic response of ACE inhibitors. Few but contradictory data exist on the effects of H2-blockers on ACE inhibitor pharmacokinetics and little information is available on interactions between ACE inhibitors and hypoglycaemic drugs. Some case reports link ACE inhibitors with the induction of lithium toxicity. Coadministration of lithium should be undertaken with caution, and frequent monitoring of lithium concentrations is recommended with all ACE inhibitors. Nonsteroidal anti inflammatory drugs (NSAIDs) may attenuate the haemodynamic actions of ACE inhibitors. NSAIDs reduce renal excretion of ACE inhibitors, with a corresponding increase in circulating drug concentrations. There is little information available on the pharmacokinetic interaction with ACE inhibitors and cyclosporin, but caution should be employed when they are used together.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8354021 TI - A systematic integrated approach to improvement of drug prescribing in an acute care hospital: a potential model for applied hospital pharmacoepidemiology. PMID- 8354022 TI - A population and family study of N-acetyltransferase using caffeine urinary metabolites. AB - Population and family studies were undertaken to validate caffeine as a probe drug to establish the genetic status of rapid acetylators and slow acetylators. The acetylator status was established from the urinary metabolic ratio of 5 acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine (AFMU/1X) after oral administration of caffeine. We confirmed a bimodal distribution (chi 2(1) = 229.48; p << 10(-9)) of the AFMU/1X ratio in 245 unrelated subjects. A third distribution did not significantly improve the fit to the data (chi 2(1) = 0.04; p = 0.84). Complex segregation analysis of 76 nuclear families confirmed the monogenic inheritance of N-acetyltransferase, with incomplete dominance of the rapid allele over the slow one. We observed a slight shift between the mean activities of heterozygous and homozygous rapid acetylators (t = 2.89; p < 0.01). However, the 30 obligate heterozygotes belonging to the 76 families were evenly distributed among the rapid acetylators and never located in a hypothetic intermediary group between slow acetylators and rapid acetylators. PMID- 8354023 TI - Inhibition and induction of cytochrome P4502E1-catalyzed oxidation by isoniazid in humans. AB - We studied the effect of isoniazid administration on the cytochrome P4502E1 catalyzed elimination of chlorzoxazone and acetaminophen. Isoniazid, 300 mg daily, was administered for 7 days to a group of 10 volunteer slow acetylators. Acetaminophen, 500 mg, and chlorzoxazone, 750 mg, were administered on separate occasions before isoniazid, during the period of isoniazid administration, and after the discontinuation of isoniazid. Isoniazid inhibited the clearance of chlorzoxazone by 58%, as assessed from plasma data, and inhibited the formation of acetaminophen thioether metabolites (a measure of the formation of the hepatotoxin N-acetyl-p-benzoquinone imine and catechol oxidative metabolites of acetaminophen, as determined from their recovery in urine, by 63% and 49%, respectively. Two days after the discontinuation of isoniazid, the clearance of chlorzoxazone was increased over the value before isoniazid by 56%. Acetaminophen thioether but not catechol metabolites were increased by 56% 1 day after the discontinuation of isoniazid and had returned to the pre-isoniazid value 3 days after the discontinuation of isoniazid. We conclude that the time course of the interaction with regard to chlorzoxazone elimination and formation is compatible with an inhibition-induction effect of isoniazid on cytochrome P4502E1. The mechanism of this biphasic effect is probably induction by protein stabilization, which results in inhibition of catalytic activity while isoniazid is present. PMID- 8354024 TI - Reproducibility of antipyrine half-lives in elderly subjects. AB - Antipyrine half-life determined on three to five separate occasions over a period ranging from 3 weeks to 1 year was highly reproducible in each of 20 elderly subjects (12 women and 8 men; mean age, 83 years). The mean within-subject coefficient of variation for antipyrine half-life was 9.6%, whereas the between subject coefficient of variation was 33.3%. These findings indicate high reproducibility of individual rates of drug metabolism in medically stable elderly subjects. PMID- 8354025 TI - The pharmacokinetics of morphine and morphine glucuronides in kidney failure. AB - The pharmacokinetics of morphine and its glucuronide metabolites were investigated in three groups of patients with kidney failure (nondialyzed, receiving dialysis, and transplantation) and compared with a group of normal healthy volunteers. Patients in all three renal groups were undergoing surgical procedures (nondialyzed group undergoing arteriovenous fistula formation, dialysis group undergoing placement of a peritoneal dialysis catheter, and the transplant group undergoing live donor kidney transplant). A sensitive, specific high-performance liquid chromatographic assay was used to quantitate morphine, morphine-3-glucuronide, and morphine-6-glucuronide. Patients with kidney failure had a significantly increased morphine area under the curve (AUC) compared with control subjects. There was also an increase in the metabolites morphine-3 glucuronide and morphine-6-glucuronide that was severalfold greater than the increase in morphine AUC. This metabolite accumulation was reversed by kidney transplantation, providing an elegant confirmation on the role of the kidney in morphine pharmacology. PMID- 8354026 TI - Reduction of 3'-azido-3'-deoxythymidine to 3'-amino-3'-deoxythymidine in human liver microsomes and its relationship to cytochrome P450. AB - The formation of 3'-amino-3'-deoxythymidine (AMT) in patients receiving 3'-azido 3'-deoxythymidine (zidovudine) and the potential role of this metabolite in zidovudine-induced toxicity was recently demonstrated by our laboratory. This study evaluated the formation of AMT versus cytochrome P450 (P450) content, cytochrome B5 (B5) content and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase activity in human liver microsomes obtained from 24 different donors. Significant interindividual differences in total P450 content and P450 reductase activity were observed, whereas no variation was observed in B5 content. Of particular importance, metabolism of zidovudine to AMT varied widely and correlated with P450 content but not with B5 content or P450 reductase activity. The apparent values for the Michaelis-Menten constant and the maximum rate of metabolism of the reaction were 46.1 mmol/L and 3.5 nmol/min/mg microsomal protein. These large variations of AMT levels as a function of P450 suggest that major interindividual differences may be observed in the pharmacokinetics and formation of this metabolite that may affect the pharmacodynamic properties of zidovudine. Potential drug-drug interactions may occur with therapeutic agents that interact with or induce P450 (zidovudine). PMID- 8354027 TI - The cardiovascular interaction between caffeine and nicotine in humans. AB - In a placebo-controlled, double-blind randomized design, we investigated the cardiovascular interaction between caffeine (250 mg intravenously) and nicotine (4 mg chewing gum) in 10 healthy volunteers, both under baseline conditions and during physical and mental stress (standing up and mental arithmetic). Caffeine alone induced a significant increase in blood pressure associated with a decrease in heart rate, whereas nicotine alone increased both blood pressure and heart rate. The combination of caffeine and nicotine increased systolic and diastolic blood pressure by 10.8 +/- 2.0 and 12.4 +/- 1.9 mm Hg, respectively. This pressor response did not differ significantly from the calculated additive effects of caffeine and nicotine on blood pressure, measuring 12.9 +/- 2.0 and 14.2 +/- 2.1 mm Hg, respectively. Heart rate and forearm blood flow also showed a similar response when the combination of caffeine and nicotine was compared with the calculated sum. During physical stress (standing up), blood pressure, heart rate, and plasma catecholamines increased in the placebo test. The pressor response to standing up was less pronounced after the combination of caffeine and nicotine compared with the sum of the separate effects (combination versus sum: delta diastolic blood pressure, 24.7 +/- 1.9 versus 35.2 +/- 2.6 mm Hg [p < 0.01]; delta mean arterial pressure, 22.1 +/- 2.0 mm Hg versus 28.6 +/- 1.6 mm Hg [p < 0.05]). The plasma catecholamine response did not differ between the combination and the sum of both drugs. During mental arithmetic, blood pressure, heart rate, and forearm blood flow increased in the placebo test. The forearm vasodilator response to mental stress was attenuated by the combination of caffeine and nicotine compared with the sum of both drugs (combination versus sum: delta forearm blood flow, -0.1 +/- 0.3 versus 1.4 +/- 0.5 ml/100 ml/min [p < 0.05]). We conclude that the combined administration of caffeine and nicotine shows additive effects on cardiovascular parameters during baseline conditions but less than additive effects during sympathoadrenal stimulation. PMID- 8354028 TI - Influence of cyclosporine pharmacokinetics, trough concentrations, and AUC monitoring on outcome after kidney transplantation. AB - To assess the importance of cyclosporine pharmacokinetics on graft outcome and acute rejection episodes, pretransplant and a total of 1868 posttransplant whole blood cyclosporine pharmacokinetic profiles were performed in 160 consecutive kidney transplant recipients. The following posttransplant pharmacokinetic risk factors were associated with a poorer graft survival and a higher incidence of acute rejection: F, < 25%; clearance, > 325 ml/min; steady-state cyclosporine concentrations, < 350 ng/ml during intravenous infusion; or average cyclosporine concentrations, < 400 ng/ml during the first oral study. Although the discrimination between rejecting and nonrejecting patients was greatest for cyclosporine concentrations obtained at 24 hours after drug administration, measurements at 6 and 14 hours, as well as average concentrations, were all highly predictive. Because of the strong association between the cyclosporine concentrations and outcome, an equation is described to provide initial oral dose prediction. Furthermore, this association suggests that improved cyclosporine pharmacokinetic monitoring may aid in improving outcome after kidney transplantation. PMID- 8354029 TI - Tricyclic antidepressants in red cells and plasma: correlation with impaired intraventricular conduction in acute overdose. AB - OBJECTIVE: Tricyclic antidepressant levels in red blood cells and plasma in acute overdose and their association with cardiotoxicity were studied. METHODS: This was a prospective study in 15 patients with acute tricyclic antidepressant overdose. Tricyclic antidepressant parent compounds and metabolites were measured in red blood cells and plasma, and tricyclic antidepressant levels were correlated with ECG indexes of toxicity. RESULTS: Plasma levels of the parent compounds were higher than their red blood cell levels on admission (mean +/- SD, 691 +/- 409 and 337 +/- 220 ng/ml, respectively). Admission metabolite levels were higher in red blood cells than in plasma (264 +/- 180 and 190 +/- 164 ng/ml, respectively). QRS duration and the red blood cell levels of the metabolites were significantly correlated at the time of admission (r = 0.77, p < 0.01), as well as at 6 to 10 hours (r = 0.74, p < 0.01). CONCLUSIONS: In acute overdose, a shift of tricyclic antidepressants from plasma to red blood cells and increased levels of red blood cell metabolites reflect tissue redistribution of the drug. Tricyclic antidepressant red blood cell metabolites are the best markers for impaired intraventricular conduction. PMID- 8354030 TI - Serotonin syndrome and drug interactions. PMID- 8354031 TI - Oral tyramine challenge tests. PMID- 8354032 TI - Nonsedating antihistamine approved by FDA. PMID- 8354033 TI - Increasing breast milk supply. PMID- 8354034 TI - Vancomycin pharmacokinetics in elderly patients. PMID- 8354035 TI - Effect of flumazenil on benzodiazepine-induced respiratory depression. AB - The ability of flumazenil to reverse benzodiazepine-induced respiratory depression is discussed through a review of the relevant literature. Flumazenil has been shown to be effective in reversing benzodiazepine-induced sedation, but its ability to reverse benzodiazepine-induced respiratory depression is controversial. Part of this controversy stems from the lack of consistent data on the incidence and nature of depressed respiratory function after benzodiazepine administration. In addition, a variety of tests are used to assess respiratory function, but because breathing is both automatic and under voluntary control, the results of some of these tests can be affected by patient effort. In such cases, improvement can result from an increased level of consciousness even though the central respiratory drive remains depressed. Thus, studies using these tests to determine flumazenil's effect on respiratory depression are inconclusive, as they do not accurately measure reversal of the central respiratory depression induced by benzodiazepines. However, studies using methods that do accurately assess central respiratory drive have involved small numbers of subjects and demonstrated a variable incidence of respiratory depression associated with benzodiazepine use. When benzodiazepine-induced respiratory depression was evident, the ability of flumazenil to reverse it was inconsistent and short-lived. Flumazenil may be able to improve breathing through improved consciousness, but its effects on central respiratory depression are inconsistent. Therefore, unless additional information becomes available supporting flumazenil's ability to reverse benzodiazepine-induced respiratory depression, it should not be used for this indication. PMID- 8354036 TI - Human gene therapy. AB - Current concepts in gene transfer and its application to the treatment of human genetic disorders, cancer, and other diseases are discussed. Gene therapy is a technique in which a functioning gene is inserted into a human cell to correct a genetic error or to introduce a new function to the cell. Many methods, including retroviral vectors, have been developed for ex vivo and in vivo gene insertion into cells. Some pharmacists have likened gene therapy to a sophisticated form of drug delivery and have envisioned an active role for the pharmacy profession. There are several safety and ethical issues related to manipulating the human genome that need to be understood. Current gene therapy efforts focus on gene insertion into somatic (nongerminal) cells only. Gene therapy has the potential to revolutionize the treatment of genetic disorders, diseases associated with a genetic component (e.g., cystic fibrosis), cancer, AIDS, and many other diseases. Gene transfer may also be used to better understand the biology of disease processes, such as the source of relapse in bone marrow transplant patients. The human genome project will undoubtedly lead to the identification, characterization, and understanding of genes that are responsible for many human diseases, and gene therapy trials are sure to expand accordingly. To date, over 40 clinical trials have been approved and more than 110 patients have been entered in gene therapy studies. There are still many technical obstacles to overcome before gene therapy can have widespread application. Injectable vectors need to be developed to simplify foreign gene administration. Perhaps the biggest problem to overcome will be engineering the target cells to be able to regulate gene expression according to physiologic needs. Pharmacists should become knowledgeable about gene transfer techniques and possible clinical applications of gene therapy to keep abreast of the newest trends in medicine. PMID- 8354037 TI - Vitamin A as an immunomodulating agent. AB - Findings on the benefits and mechanism of action of vitamin A in measles and other infectious diseases and immunocompromised states are discussed. Vitamin A deficiency is one of the world's major malnutrition problems and is most commonly found in children under the age of five years. An association between vitamin A status and immune function has been suggested by community studies and animal experiments. Mortality and susceptibility to infection and diarrhea are higher in children with vitamin A deficiency. The association between increased mortality and morbidity and vitamin A deficiency is strongest in children with measles. Vitamin A supplementation reduces mortality and complications resulting from measles. Measles may increase the body's utilization of vitamin A, possibly because of the rapid destruction of epithelial surfaces. Vitamin A may boost immune responses in the elderly, persons with high exposure to ultraviolet light, patients who have undergone surgery, and persons with parasitic infection, but more studies are needed. The immune defect caused by vitamin A deficiency may be due to alterations in the glycoproteins of the lymphocyte membrane, an adverse effect on helper T-cell function, the effect on epithelial tissue, or some other mechanism. Vitamin A therapy is relatively safe, and its effectiveness in children with measles and possibly other groups appears to justify public health campaigns to eliminate vitamin A deficiency. Vitamin A apparently has important immunomodulating properties, notably in patients with measles. PMID- 8354038 TI - Vancomycin pharmacokinetics and dosage requirements in hematologic malignancies. PMID- 8354039 TI - Adverse effects of molgramostim in marrow transplant recipients. PMID- 8354040 TI - Lidocaine therapy: time for re-evaluation. PMID- 8354041 TI - MEDWatch: the new FDA medical products reporting program. PMID- 8354042 TI - Criteria for use of flumazenil in adult inpatients and outpatients. PMID- 8354043 TI - [Treatment of pulmonary embolism. Current status and future prospects]. AB - Although still severe, the prognosis of pulmonary embolism has recently improved due to considerable progress in the therapeutic field. This paper concerns the various therapeutic tools, both pharmacologic and surgical, which are already available or under evaluation. Despite the introduction of thrombolytic drugs, heparin remains an indispensable drug. The rationale for its use comes from the need of preventing further clot formation, while endogenous fibrinolysis or thrombolytic drugs are dissolving the already existing clots. Thrombolytic drugs, such as streptokinase, urokinase or rt-PA, have changed the therapeutic strategy of pulmonary embolism, due to their ability to accelerate the normal fibrinolytic mechanisms and to facilitate pulmonary reperfusion. This often allows an early disappearance of symptoms and a reduced incidence of invalidating complications involving the respiratory function. rt-PA seems to be most effective and fast in inducing reperfusion (angiographic signs of clot dissolution are obtained in 82% of the patients within 2 hours). The administration of rt-PA by intravenous bolus has recently been proposed, which would induce an even faster thrombolysis and fewer hemorrhagic complications. The role of surgical therapy has declined after the diffusion of thrombolytic drugs, being reserved only for the most serious cases. When anticoagulation is counter-indicated or not effective, the prevention of embolic relapses can be achieved by percutaneous insertion of caval filters of different types. Some new catheters provided with rotating metallic tips, which allow the mechanical fragmentation of the emboli, are presently under evaluation. Although some improvements are needed, this technique is expected to become soon of general use, especially in cases in which thrombolytic therapy is counter indicated. PMID- 8354044 TI - Chronic obstructive pulmonary disease. A possible correlation between platelet aggregation tests and respiratory indexes. ECOB Group. AB - It has been suggested that thrombotic events occurring in patients with chronic obstructive pulmonary disease could be partially due to abnormalities in blood coagulation and fibrinolysis, as well as to changes in platelet function. In the present study in vitro platelet aggregation, in addition to clotting activity, has been studied in 20 patients with chronic obstructive pulmonary disease and different degrees of alteration of blood gas analysis. The results obtained suggest that the presence of a condition of platelet hypoaggregability characterizes patients with marked hypercapnia and/or hypoxemia, whereas the improvement of respiratory indexes is followed by a trend to normalization, or, more often, to an increase of platelet activity. PMID- 8354045 TI - [Efficacy and tolerability of cisapride in a new formula of 10 mg effervescent capsules for the treatment of functional dyspepsia]. AB - The efficacy and tolerability of Cisapride effervescent granules and a metoclopramide-dimethicone combination were compared double-blind in two comparable groups of 15 patients each with dyspepsia. All patients received three sachets daily of either drug for 6 consecutive weeks. As for efficacy, Cisapride effervescent granules was found to reduce 85% (11/13) of symptoms to a statistically significant extent, as against 42% (5/12) in the reference group. Statistical analysis showed Cisapride effervescent granules to be more effective than the reference drug for 6 out of 11 evaluable symptoms. Mean global improvement was 86% for Cisapride effervescent granules vs 41% for the reference combination. Final judgment by the physician was more favorable for Cisapride effervescent granules than for the reference drug (p < 0.0001). Treatment withdrawal was never necessary and no significant changes of laboratory values were observed. No statistically significant difference between the two treatments as to tolerability was observed. In conclusion, Cisapride effervescent granules was found to have a better risk/benefit ratio than the reference combination. PMID- 8354046 TI - [Effectiveness of loratadine vs. placebo in the treatment of urticaria-angioedema syndrome in patients with food allergy]. AB - Loratadine is a new, highly selective, non sedating, H 1-receptor antagonist, without central nervous system activity. In a randomized double-blind, crossover study, we evaluated the effects of loratadine and placebo administered once daily in 184 food intolerant patients affected by urticaria-angioedema. The difference between loratadine and placebo treatment was significant in relieving symptoms. Adverse reactions reported in the treatment were mild, in fact somnolence was reported by 3.4%, dry mouth by 2.2% of patients. PMID- 8354047 TI - [Efficacy and tolerability of ketoprofene administered through iontophoresis in rheumatoid arthritis. Results from a multicentric study]. AB - Three-hundred and twelve patients with osteoarthritic diseases were admitted to a multicenter clinical trial. The patients were given 100 mg Ketoprofen twice-a-day by iontophoresis for 10 consecutive days. Pain relief was almost complete in 94.6% of the patients, improvement of active motility in 83.6%, disappearance of swelling in more than half of the patients and functional improvement in about all the cases. Two allergic skin reactions of a mild degree (0.6%) were registered. Therefore, Ketoprofen administered by iontophoresis showed to be efficacious and safe in the treatment of acute osteoarthritic diseases also in high risk patients. PMID- 8354048 TI - [Aortic dissection: the role of diagnostic imaging, with special reference to magnetic resonance imaging and its implications in the pathogenesis]. AB - The aim of this work was to evaluate the usefulness of angiography, CT scan and MR imaging in the diagnosis of aortic dissection, on the basis of the authors' experience and literature review. Angiographic study is still considered the first choice technique in the diagnosis of aortic dissection, although it is considered not completely safe. CT scan allows to note the early thickening of the vessel walls (due to intraparietal bleeding) and the presence of calcifications in the thrombosed portion of the lesion. MR study allows multiplanar study of the lesions without contrast medium, and best visualization of subendothelial bleeding in dissections without intimal lesion. PMID- 8354049 TI - [The CADIZ program]. PMID- 8354050 TI - Inversion and configuration of faces. AB - If the mouth and eyes of a face are inverted, the altered construction appears grotesque when upright, but not when upside-down. Three studies of this "Thatcher illusion" employed faces that were grotesque when upright because: (a) their eyes and mouths had been inverted ("Thatcherized" faces), (b) their eyes and mouths had been moved (spatially distorted faces), or (c) they had grotesque posed expressions. Inversion reduced the apparent grotesqueness of both Thatcherized and spatially distorted faces, but not grotesque-expression faces. Moreover, Thatcherized and distorted faces, although not grotesque-expression faces, were judged as more similar to normal, smiling faces when face-pairs were inverted than when they were upright. Similarity ratings to inverted face-pairs were correlated with latencies of response to these pairs in a task that encouraged attention to components (e.g., mouths, eyes) rather than wholistic properties. Similarity ratings to upright face-pairs showed no such correlation, and this and other findings suggested that although similarity ratings to upright faces are based on wholistic information, similarity ratings to inverted faces are based largely on components. The Thatcher illusion reflects a disruption of encoding of wholistic information when faces are inverted. PMID- 8354051 TI - Mental rotation, mental representation, and flat slopes. AB - The "mental rotation" literature has studied how subjects determine whether two stimuli that differ in orientation have the same handedness. This literature implies that subjects perform the task by imagining the rotation of one of the stimuli to the orientation of the other. This literature has spawned several theories of mental representation. These theories imply that mental representations cannot be both orientation-free and handedness-specific. We present four experiments that demonstrate the contrary: mental representations can be both orientation-free and handedness-specific. In Experiment 1 we serendipitously discovered a version of R. N. Shepard and J. Metzler's (1971) "mental rotation" task in which subjects accurately discover the handedness of a stimulus without using "mental rotation," i.e., in which reaction time to compare the handedness of two forms is not a function of the angular disparity between the two forms. In Experiment 2 we generalize this finding to different experimental procedures. In Experiment 3 we replicate this finding with a much larger group of subjects. In Experiment 4 we show that when we preclude the formation of an orientation-free representation by never repeating a polygon, subjects carry out the handedness comparison task by performing "mental rotation." PMID- 8354052 TI - Adequacy of treatment of uremia in the nineties. PMID- 8354053 TI - Adequacy of hemoperfusion for blood purification in uremia. PMID- 8354054 TI - Quality of membrane. High flux membrane and its future. PMID- 8354055 TI - Advantages of meltspun membrane technology compared to solution spinning. PMID- 8354056 TI - Computerized monitoring of dialysis. PMID- 8354057 TI - Hemodynamic criteria for adequacy of volume regulation and prevention of myocardial impairment in chronic hemodialysis patients. PMID- 8354058 TI - Hybrid bioartificial kidney: pitfalls and present state of the art. PMID- 8354059 TI - Supplemented dialysis: amino acid-based solutions in peritoneal dialysis. AB - Peritoneal dialysis is associated with several metabolic and nutritional abnormalities, some of which are related to the use of glucose-based solutions. Furthermore, the catabolic effects of uremia per se, protein and amino acid losses into the dialysate, peritonitis and poor appetite contribute to amino acid abnormalities, negative nitrogen balance and a high prevalence of malnutrition in peritoneal dialysis patients. To overcome these problems the use of amino acid instead of glucose as an osmotic agent has been proposed. Short-term studies have shown that amino acid-based solutions in peritoneal dialysis may supplement in excess the daily losses of amino acids during dialysis with glucose-based solutions. The amino acid solutions produce similar ultrafiltration and solute transport as the standard glucose solutions although the period of effective ultrafiltration is rather short. However, it should be noted that some studies have reported that the transport of small and large solutes may increase in patients using amino acid solutions. During the early 1980s several investigators have developed and tested different amino acid solutions for peritoneal dialysis. The initial clinical experience from Toronto with amino acid solutions containing large amounts of non-essential amino acids and inadequate amount of buffer were in general discouraging. The patients, who were not always malnourished and tended to have a low energy intake, developed increased BUN levels, acidosis, no improvement in nutritional status or amino acid abnormalities and, in some cases, anorexia. In 1985 a new 1% amino acid solution, containing an increased buffer amount and amino acids (mainly essential) in proportions which take the amino acid abnormalities in uremic patients into account, became available. The use of this solution resulted in some improvement in amino acid pattern and nutritional parameters, but acidosis and increased BUN levels remained problems. The experiences from these and previous studies showed that: (1) the improvement of the composition of amino acid solutions was beneficial; (2) a further increase of the buffer amount was needed; (3) patients included should have signs of protein malnutrition combined with low dietary protein intake to benefit from intraperitoneal amino acid supply, and (4) energy intake should be sufficient to prevent amino acids to end up as energy source. For this purpose a new improved 1.1% amino acid solution has been developed containing a further increase of some essential amino acids and an increased amount of lactate (40 mmol/l). This solution has been tested in malnourished patients eating 0.8 g protein/kg/day and 25-30 kcal/kg/day.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8354060 TI - The new bionic era in renal replacement therapy. PMID- 8354061 TI - What is adequate CAPD? PMID- 8354062 TI - Biocompatibility: methodology and evaluation. PMID- 8354063 TI - Biocompatibility of dialysis membranes. PMID- 8354064 TI - Approach to dialysis biocompatibility: evaluation through in vivo investigation of lymphocyte biology. A technical note. PMID- 8354065 TI - Dialysate biocompatibility: evaluation and expectations. PMID- 8354066 TI - High-flux dialysis, dialysate quality and backtransport. PMID- 8354067 TI - Quality of life and adequacy of dialysis. PMID- 8354068 TI - Studying the culture and effectiveness of biomedicine. PMID- 8354069 TI - Perspectives on the health and health care of Canada's first peoples. PMID- 8354070 TI - Micro-anatomo politics: mapping the Human Genome Project. PMID- 8354071 TI - An introduction to cultural and social studies of sciences and technologies. PMID- 8354073 TI - Galton's regret and DNA typing. PMID- 8354072 TI - The development of property rights in biotechnology. AB - The translation of biological theory into engineering (biotechnology) has resulted in the development of novel products and processes. Some of these products are living organisms, usually containing unique genetic arrangements not found in nature. The extension of legal protection to products and processes was required in order for biotechnology to become an unexceptional way in which to do business. The American experience with biotechnology, repeated elsewhere, is demonstrated to have proceeded first through the negotiation of obstacles in administrative law and second through challenges to property law. This outcome for the regulatory management of biotechnology and the legal protection of its products may be interpreted as a function of a cultural bias for scientific authority and progress ideology. PMID- 8354074 TI - Histories of immune systems. PMID- 8354075 TI - Psychoneuroimmunology: the problem of the situatedness of illness and the conceptualization of healing. AB - Psychoneuroimmunology claims to go beyond narrow biological perspectives of illness to consider behavioral components as an integral part of health and disease. The conceptualization of the embodiment of behavioral dimensions and how they may be represented in terms of interaction between the central nervous system and the immune system are therefore central theoretical issues. Psychoneuroimmunology is thus an arena in which questions about the body and person in context should come to the fore. There are multiple approaches in the psychoneuroimmunological literature, including those which attempt to address in some fashion the issue of the situatedness of illness. It is argued here that the problem of the representation of situatedness is the primary axis of tension in current research and writing in psychoneuroimmunology. Diverse attempts to represent extremely complex (and non-linear) relationships between behavioral and biological dimensions of 'immune system' functioning drive a number of researchers, though they operate under disciplinary, institutional, and funding constraints in the U.S. which tend to work against the development of competing or radical models within psychoneuroimmunology itself. PMID- 8354076 TI - A cultural analysis of human behavioral breakdowns: an approach to the ontology and epistemology of psychiatric phenomena. AB - This paper explores the usefulness of a concept of "human behavioral breakdowns" for studying psychiatric phenomena from a cross-cultural standpoint. The kinds of conceptualizations that are available in the English literature about human behavioral breakdowns across societies are reviewed. The way these breakdowns have been handled in the Western European Tradition of medicine is given special emphasis. Attention is focused on schizophrenia as one of the modern "disease" concepts of psychiatry that is a variant of human behavioral breakdowns. The essay then looks at "schizophrenia" using contemporary ideas about cultural relativism as these apply to the study of psychiatric phenomena in relation to society. Perspectives about the variable as versus the invariant in schizophrenia are reviewed. PMID- 8354077 TI - Group A streptococcal infections--1993. PMID- 8354078 TI - Pediatric immunizations. AB - The record of disease prevention in children is an impressive testament to our universal immunization program. However, these successes are being threatened by rates of vaccination in some areas of the country that are substantially less than those seen in the developing world. Unless the pediatric immunization rates are improved, epidemics of other vaccine-preventable diseases will recur, as evidenced by the measles outbreaks. Although the tools needed for disease prevention are available, the means for their delivery are lacking. It is the obligation of us all to immunize the nation's children. PMID- 8354079 TI - Vascular disorders of the upper torso. PMID- 8354080 TI - Neutralization of animal viruses. PMID- 8354081 TI - Neonatal and infantile acne vulgaris. PMID- 8354082 TI - Black dermographism: mechanism for formation of black color. PMID- 8354083 TI - A dermatologic diary. Portrait of a practice. PMID- 8354084 TI - Psoriasis associated with human immunodeficiency virus/acquired immunodeficiency syndrome. AB - Since the prevalence of psoriasis is between 1.5 to 2 percent, it would be expected to occur by chance in a person infected with HIV who is genetically predisposed to psoriasis. Several studies in the literature on HIV/AIDS associated psoriasis have reported such percentages of frequency. Although psoriasis is a low priority for a patient with HIV/AIDS who is coping with many other cutaneous conditions and cancers, when treating the HIV/AIDS-infected psoriatic patient, immunosuppressive drugs are contraindicated because of their serious impact on an already immunodeficient person. PMID- 8354085 TI - Metastatic umbilical carcinoma: the Sister Joseph's nodule. AB - Metastatic umbilical carcinoma has been referred to by generations of physicians as Sister Joseph's nodule. Though not common, this characteristic lesion is important to recognize and properly evaluate. We present a case of an eighty-two year-old woman with a Sister Joseph's nodule due to an unknown primary carcinoma, and we review the diagnostic and prognostic features of umbilical metastases. PMID- 8354086 TI - Aggressive sebaceous carcinoma of the eyelid: an elusive diagnosis. AB - Sebaceous carcinoma of the eyelid, an extremely rare neoplasm, can resemble blepharitis, conjunctivitis, or chalazion, as in the case presented here. A biopsy specimen should be examined if these conditions fail to respond to therapy, especially if the lesion is unilateral. The tumor can be multifocal, and pagetoid proliferation is common. Therefore, recurrences are common after conservative surgery, even if frozen sections are obtained from the margins. Orbital exenteration may be necessary to prevent metastasis. PMID- 8354087 TI - Unusual erythema of the proximal nail fold and onychodermal band. PMID- 8354088 TI - Epidermodysplasia verruciformis: report of a case with palmar pits. AB - A case of epidermodysplasia verruciformis is reported. This rare disease is characterized by a generalized eruption of flat warts and lesions resembling pityriasis versicolor. Epidermodysplasia verruciformis is considered to represent a distinctive pattern of abnormal reactivity to the human papillomavirus. Our patient, in addition to showing the classic skin lesions, exhibited pitlike lesions of the palms. PMID- 8354090 TI - [Oral glucose tolerance test in late pregnancy women]. AB - A total of 514 pregnant women had oral glucose tolerance test (OGTT) with 75g glucose load performed between 24 and 37 weeks of gestation. They were divided into 2 groups. Group I (n = 350) was normal pregnant controls. Group II (n = 164) was at high risk of DM group. With pooled data the results of OGTT from group I, a statistically derived criterion (based on 97.5 percentile approximated to the nearest 5) was devised. This criterion defines the lower limits of abnormal values for venous plasma glucose in Chinese pregnant women during an OGTT with a 75g glucose load as follows: fasting 5.5 mmol/L, 1 hour 10.2 mmol/L, 2 hours 8.2 mmol/L, 3 hours 6.6 mmol/L. These values are lower than those recommended for pregnant women by NDDG and WHO. It is a question whether the criterion derived from data in caucasian population are fit for the population in developing countries. Serum insulin release test were performed in 81 of 350 pregnant women in group I. The results showed that serum insulin release levels after a glucose load in late pregnancy were more active than those in the non-pregnant state. OGTT in women of group II with high risk of GDM showed to be more intolerant compared with those women in group I. PMID- 8354089 TI - [Changes in plasma and urinary digoxin-immunoreactive like substance in normal pregnancy and pregnancy-induced hypertensive women]. AB - Plasma and urinary digoxin-immunoreactive like substance (DILS) were measured in normal non-pregnant (NNP), normal pregnant (NP) and pregnancy-induced hypertensive women (PIH). The plasma DILS level of PIH, compared with NNP, was no significantly decreased (P > 0.05); but that of NP was significantly decreased (P < 0.01). While the urinary DILS levels of PIH and NNP were significantly higher than that in NNP (P < 0.01). In 24-72 hours after delivery the plasma and urinary DILS levels were all significantly lower than that in NNP (P < 0.05). These results indicate that DILS may play a role in homeostasis regulation in NP or PIH. PMID- 8354091 TI - [Clinical analysis of perinatal outcome in gestational diabetes]. AB - This retrospective study was carried out on 78 women with gestational diabetes during Nov. 1982-Oct. 1991. The study indicates that treatment of gestational diabetes can reduce the occurrence of macrosomia. Macrosomia occurred in 19.35% of the insulin-treated group, 21.05% of the diet-treated group, and 50% of the untreated group. Neonatal morbidity was decreased in good diabetic control group. A routine prenatal "50g glucose screen" in pregnant women with high-risk factor should be carried out in order to make early diagnosis of gestational diabetes. Delivery time should be choosen during 38-40 weeks of gestation. PMID- 8354092 TI - [Immunologic diagnosis and treatment in the cases of unexplained habitual abortion]. AB - One hundred and fourty-eight cases of habitual abortion were screened for etiologies. We found 40.5% (60/148) were unexplained. Among them, 34 cases were volunteers for receiving repeated active immunolization with low-dose of lymphocyte from their husbands or other donors, and 12 cases were taken as control. The successful pregnant rate was 86.4% (19/22) in treatment group which is higher significantly than in control (P < 0.05). meanwhile, used by microlymphocytotoxic antibody test and one-way mixed lymphocyte reaction and its inhibition test, the observations on immunologic state before and after vaccination were made in 19 cases. We found both the positive rate of microlymphocytotoxic antibody test and the relative suppressive rate of lymphocyte response were increased significantly post-vaccination than pre vaccination. These results not only confirmed that active immunization was effective, but also suggested that habitual abortion may be associated with the lack of protective antibody and/or block antibody. PMID- 8354093 TI - [Menstrual status as risk factors of endometriosis: a case-control study]. AB - A case-control study, involving 203 cases of pelvic endometriosis and 406 randomly selected and age-matched community controls, was conducted. The results showed that women characterized by earlier menarche (< or = 12 years) and longer period (> 7 days) were associated with an elevated risk. Longer cycle (> 35 days) seemed to have a protective effect. There are a tendency to increasing risk for endometriosis associated with primary dysmenorrhea and energetic physical activities during menstruation. The results indicate that intensive treatment of primary dysmenorrhea and avoidance of strenuous exercise during menstruation may prevent pelvic endometriosis. PMID- 8354094 TI - [Prognostic factors of endometrial carcinoma: a study of 98 cases]. AB - Ninety-eight cases of endometrial carcinoma treated in our hospital during 1965 1988 were reviewed. The 5-year survival rate was 64.3%. Many factors were found to be related to 5-year survival: clinical stage, histological type, histological grade, depth of myometrial invasion and the amount of lymphocytic infiltration around islands of tumour cells. Earlier clinical stage, higher histological grade and less myometrial invasion had more favorable prognosis. Adenocarcinoma and adenoacanthoma had more favorable prognosis when compared with adenosquamous carcinoma and papillary adenocarcinoma. The more the amount of lymphocytic infiltration, the better prognosis. No correlation was found between the 5-year survival rate and the uterine size, the therapeutic modality, the age, parity, menstrual state of patient. PMID- 8354095 TI - [Cytotoxicity of recombinant human tumor necrosis factor (rHTNF) alone and in combination with chemotherapeutic agents on human ovarian cancer cells]. AB - The cytotoxic activities of recombinant human tumor necrosis factor (rHTNF) and five chemotherapeutic agents, CTX, 5-FU, VCR, DDP, KSM, against two human ovarian cancer cell lines, OVCAR3 and CAOV3, using the MTT assay were studied. The result showed that cytotoxicities of rHTNF at 5 x 10(4)-5 x 10(7) U/L against CAOV3 cell line for 24h exposure were from 14.2% +/- 6.8% to 67.2% +/- 3.0%, and that against CAOV3 cell line were from 8.2% +/- 4.3% to 60.9% +/- 1.3%. The cytotoxic effects of all five chemotherapeutic agents against the two cell lines were much lower than that of rHTNF. Various degrees of synergistic enhancement cytotoxicities of DDP or KSM in combination with rHTNF were assessed. Especially, distinct synergistic effects of a low dose, 50kU/L, or rHTNF with nearly all concentration (10(-4)-10(-1) mg/L) of KSM were obtained on the two cell lines. PMID- 8354096 TI - [Pregnancy induced hypertension and calcium deficiency]. PMID- 8354097 TI - [Radioimmunoscintigraphy in the diagnosis of early and recurrent ovarian cancers]. PMID- 8354098 TI - The feedsideward of cephalo-adrenal immune interactions. AB - The feedsideward phenomenon is the interaction of three or more rhythmic physiological entities by a diversified spectrum of rhythms that constitute a rhythmic network. These rhythmic units are: a) the modulator, b) the actor, c) the reactor and d) the integrative unity. Rhythmic interactions are characterized by an alternating sequence of algorithmically predictable effects of attenuation, no effect, and stimulation occurring in different frequencies. The basis of this phenomenon was determined from experimental evidence derived from cephalo-adrenal ex vivo studies. Internal phase-shift studies allow the demonstration ex vivo of a collateral hierarchy of rhythmic neuro-endocrine interactions as alpha, beta, gamma and delta rhythms. Linear least squares analyses describe and quantify circadian (alpha, beta and gamma) and infradian (delta) rhythms in the original series and the differences in responses [beta-alpha] and [gamma-delta]. These spontaneous and response rhythms reveal a collateral neuro-endocrine hierarchy and validate a pineal feedsideward phenomenon. Circadian-infradian murine rhythmic intermodulations are demonstrated in the epithelial corneal mitosis; brain neurosteroids and pineal melatonin content. A circadian rhythm in pineal melatonin content in female B6D2F1 mice and the chronomodulating action of melatonin + ACTH upon adrenal corticosterone production are confirmed. A chronopilot ex vivo study "suggests" that melatonin chronomodulates mouse aldosterone production. In a second chronopilot study, HrIL-2 chronomodulates rat corticosterone production ex vivo. Feedsidewards in vivo were seen in the chronomodulation of tumor-host balance occurring after melatonin, IL-2, cefodizime, and cyclosporine treatments that enhanced or delayed tumor growth and survival time of tumor-bearing mice. PMID- 8354099 TI - Beyond circadian chronorisk. PMID- 8354100 TI - More on chronomes: circaseptans and circasemiseptans in Marburg, Germany, and 47 other locations. PMID- 8354101 TI - Relationship between activity levels and circadian blood pressure variations. AB - In 17 healthy Japanese students (14 males and 3 females) an ambulatory activity level monitoring instrument (Actigraph) was attached to the wrist for 48-hour measurement of wrist movement (with 0.01G or higher acceleration). At the same time, an ambulatory blood pressure monitoring apparatus was attached to these subjects to monitor blood pressure (BP) and heart rate (HR) every 30 minutes. Sleeping hours were calculated from the activity levels. The sleeping hours obtained by the Actigraph correlated with those judged from the diary. The correlation was better for the go-to-sleep time than for the awakening time. Activity level, HR and BP showed a similar circadian variation. Activity level differed significantly between the active daytime (4500 counts/hour) and during sleep at night (720 counts/hour). The acrophase of activity level, obtained by the cosinor method, was 235 degrees which did not significantly differ from that of BP and HR. Hourly activity levels correlated with HR and BP at corresponding hours. These results suggest that BP is affected by activity levels even if this rhythm continues to recur in bedrest. PMID- 8354102 TI - Circadian stage-dependence of acetyl-L-carnitine effects on blood pressure and heart rate of clinically healthy subjects. PMID- 8354103 TI - Repeated alcohol intake changes circadian rhythm of ambulatory blood pressure. AB - The blood pressure of 7 clinically healthy volunteering social drinkers was studied while they consumed, with a crossover design for 5 days, either 40 g of alcohol by day or fruit juice, with the two spans on alcohol and juice being separated by a one-week washout. Whereas the rhythm-adjusted mean was not changed, a clear statistically significant increase in the circadian double amplitude was found. The study provides a model for a rapidly achieved circadian amplitude hypertension which may precede an elevation of the overall blood pressure mean in the natural course of the disease. PMID- 8354104 TI - Beyond circadian chronorisk: worldwide circaseptan-circasemiseptan patterns of myocardial infarctions, other vascular events, and emergencies. PMID- 8354105 TI - [Structural basis of mutagenicity of heterocyclic amines]. AB - The CASE (computer-automated structure evaluation) was used to gain an understanding of the basis of mutagenicity of heterocyclic amines. It was found that the activity of these molecules was dependent upon the amino connected with the carbon in the benzene cycle, and the position of nitrogens in the heterocycle was also important. Both the sensitivity and specificity of the CASE system established in my laboratory approached 1.00. PMID- 8354106 TI - [The causes for hyporeactiveness of vaccination against hepatitis B and the strategies to resolve the situations]. PMID- 8354107 TI - [The use of decision making analysis for evaluating hepatitis B inoculation strategy]. AB - Using quality adjusted life year (QALY) as an evaluation measure of cost effectiveness for assessing hepatitis B inoculation strategy in China, through the decision tree model. The result showed that for hepatitis B inoculation, priority should be given to neonates and infants aged 0-3 years; and the age of vaccination subjects be extended to, adults older than 25 yrs. The result also indicated: that the net cost for each QALY gained due to vaccination was very high, so that the ultimate control of hepatitis B epidemic not only depended on the development of highly effective and inexpensive vaccine, but also on the improvement of economic level and sanitary status. PMID- 8354108 TI - [Immune-efficacy of recombinant vaccinia HB vaccine on middle school students of Uigur nationality]. AB - Immunization efficacy of HB vaccine which is gene engineering vaccine of vaccinia virus recombinant was studied. A total of 206 middle school students of Uygur nationality in Hami, Xinjiang was vaccinated. A varying dosage of 10 micrograms, 5 micrograms, and 2.5 micrograms and 0, 1, 2 months schedule was carried out. The results showed that a seroconversion rate of 100%, 92.4% and 83.5%, in respect to 10 micrograms, 5 micrograms and 2.5 micrograms dosages were found while the mIU/ml values were 129.25, 132.27 and 121.18 respectively. The difference between seroconversion rates of 10 micrograms and 2.5 micrograms was significant (P < 0.05), whereas, that between conversion rate due to 10 micrograms and 5 micrograms was not (P > 0.05). Results in a year after primary immunization showed seroconversion rates of the three groups being 97.10%, 89.80% and 76.00% (P < 0.05); mIU/ml value were 151.0, 95.2 and 71.6 (P < 0.01), showing that the 10 micrograms group gave superior results to the 5 micrograms and 2.5 micrograms groups. PMID- 8354109 TI - [Effects of cereals from Kaschin-Beck's disease endemic area on fibrillogenesis in vitro of cartilage type II collagen in rats]. AB - In this feeding trial, rats were fed with diets of (a) cereals from Kaschin Beck's Disease (KBD) endemic area, (b) Sesupplemented cereals from the area as above, (c) cereals from non-KBD endemic area. The purpose of this experiment was to study the effects of cereals from KBD endemic area and Se on the kinetics of formation of cartilage type II collagen fibril, the stability and ultrastructure of fibrils formed in vitro. The results indicated that feeding of low-selenium cereals from KBD endemic area may cause decelaration of rats cartilage type II collagen fibrillogenesis, reduction of stability of fibril, diminishing of fibril diameters, and increase or decrease of fibril banding periods. Sesupplemented cereals from KBD endemic area partially rectified the pathologic changes mentioned above. These observations are important for further study on the etiology and pathology of KBD. PMID- 8354110 TI - [Health effects on workers exposed to low concentration carbon monoxide at high altitude]. AB - Workers exposed to carbon monoxide (CO) at a concentration of 26.8mg/m3 at an altitude of 2,300 metres above sea level were compared with a control group of local inhabitants. There were significant differences in symptoms of headache, vertige fatigue and weakness memory impairment, insomnia, palpitation and neurobehavioral functions. CO concentration in respiratory air and HbCO in blood was higher but partial pressure of oxygen (PO2) and saturation of oxygen (SaO2) in blood was lower in the exposed group than the control group. Self-comparison of CO in respiratory air and HbCO in blood was higher after work than before work. Neurasthenia rate was significantly higher but PO2 and SaO2 significantly lower at high altitude than in the plain. The results indicated that under same CO concentrations the hazards to workers at high altitude were greater than to those working in the plain. The author recommends that at high altitude the CO permissible level should be appropriately lowered. PMID- 8354111 TI - [Multidimensional assessment study on the health and functional status of elderly in Xicheng district of Beijing City]. AB - This paper evaluates the health and functional status of the elderly in four dimensions, i.e. social support, mental health, physical health, activities of daily living (ADL). The results indicated: a) the ability to live independently was the most important health problem of the elderly in urban area; b) In the elderly, the mental health, physical health and ADL were closely interrelated, social support had various positive effects on the three other dimensions mentioned above; c) income, sex, age and employment history were four important demographic and socioeconomic factors influencing the health and functional status of the elderly. The results also indicated that mean Ridit and the cumulative impairment score are two useful indices for evaluating health and function. PMID- 8354112 TI - [Study on determinationing the bone mineral content as diagnostic value for occupational fluorosis]. AB - The results of determination of the bone density of 194 workers exposed to fluorine by SPA-III type osteodensimeter were compared with people unexposed to fluorine, and with the results of diagnosing the luorosis by X-ray. (1) The abnormal bone cortex thickness and density rate in the people exposed to fluorine was significantly higher than the ordinary people (P < 0.05). (2) In the people exposed to fluorine, the correspondency rate of determining fluorosis of bone by X-ray and by osteodensimeter were 84.6%, and results of the two methods had no significant difference (P > 0.05). (3) In another group of 155 cases, whose values of hair fluorine and urinary fluorine were higher than the ordinary people (66.5%), the abnormal density of bone of 103 cases had been determined by osteodensimeter, but not by X-ray. This showed that the diagnosis of early changes of osteofluorosis by osteodensimeter was more sensitive than by X-ray. (4) There was close association between the unusual rate of osteodensity and the superstandard rate of hair fluorine and urinary fluorine. The above findings indicated the determination of bone density can be used as a diagnostic index for occupational fluorosis. PMID- 8354113 TI - [Study of total lead exposure on a hazard to the health of children]. AB - This study of total lead exposure on 128 children from four kindergartens in Beijing and 194 children from two townships in the suburb of Beijing, all aged between 5 and 6.5 years, showed that the urban children had higher blood lead levels (0.375 mumol/L, 7.77 micrograms/dl) than their teachers' (0.223 mumol/L, 4.63 micrograms/dl) by 67.4%. While suburban children had higher blood lead levels (0.594 mumol/L, 12.3 micrograms/dl) than their mothers' (0.299 mumol/L, 6.19 micrograms/dl) by 98.7%. There was approximately 72.5%-74.7% of suburban children whose blood lead levels were well over 0.483 mumol/L (10 micrograms/dl) and 23%-25% were above 0.724 mumol/L (15 micrograms/dl). Suburban children had higher FEP levels and an abnormal rate of FEP than urban children. The lead levels taken in through diet by suburban children were higher (43.7-85.9 micrograms/day per child) than urban children (29.3 micrograms/day per child). As the main source of lead came from foodstuff and air, 90%-98% of lead was taken in with food, of which 89% came from intake of cereals and vegetables. There was a significant correlation between the blood lead levels, the practical intelligence quotient (IQ), and the visomotor integration based upon the survey of the two groups of children. The results showed that the lead exposure poses a significant hazard to the health of children in Beijing. PMID- 8354114 TI - [Study on cadmium load and calcium deficit]. AB - The effects of cadmium given by intraperitoneal injection on calcium absorption and calcium balance in rats were investigated. The results showed that intestinal calcium absorption rate decreased steadily with increasing cadmium load. When the cadmium load exceeded 9.0 mg, the average calcium absorption fell into negative value and thus led most of the rats to calcium deficit. It suggested that the negative calcium balance in rats was caused mainly by way of fecal excretion rather than the urinary route, since the calcium loss via the intestinal tract surpassed that via the urinary tract. The excess of urinary calcium (hypercalciurea), which appeared concurrently with that of feacl one's has, however, the same significance of indicating the calcium loss, so it can be referred to an indicator of calcium deficit. Our results gave no support to the view that calcium deficit and skeletal lesion were resulted from the calcium loss by urinary way. In the study, we found that there was negative correlation between cadmium burden and calcium balance, and there was remarkable dose response relationship between cadmium burden and the rate of calcium deficit. PMID- 8354115 TI - [Effects of water hardness and salt intake on the formation and disappearance of experimental atherosclerosis]. AB - The present study examined the effects of water-hardness and salt-intake, both of which were higher in north China than in the south, on experimental atherosclerosis in quail. At the end of the experiment atherosclerotic lesions in the high-salt groups were found to be more marked than those in the low-salt groups. No significant difference in total cholesterol value was found between the two groups. There was a significant positive correlation between the degree of atherosclerosis and serum-sodium value (r = 0.501, P < 0.01). There was no difference in all values between hard-water or soft-water groups. Our study suggested that high salt-intake stimulated and enhanced the formation of atherosclerosis while it delayed and impeded its disappearance, but water hardness did not. PMID- 8354116 TI - DNA cytometry consensus conference. PMID- 8354117 TI - Guidelines for implementation of clinical DNA cytometry. International Society for Analytical Cytology. PMID- 8354118 TI - Consensus review of the clinical utility of DNA cytometry in bladder cancer. Report of the DNA Cytometry Consensus Conference. PMID- 8354119 TI - Consensus review of the clinical utility of DNA cytometry in carcinoma of the breast. Report of the DNA Cytometry Consensus Conference. PMID- 8354120 TI - Consensus review of the clinical utility of DNA flow cytometry in colorectal cancer. PMID- 8354121 TI - Consensus review of the clinical utility of DNA flow cytometry in neoplastic hematopathology. PMID- 8354122 TI - Consensus review of the clinical utility of DNA content cytometry in prostate cancer. PMID- 8354123 TI - The homing cursor: a tool for three-dimensional chromosome analysis. AB - When studying the three-dimensional shape of prophase chromosomes (or any other tubular structure), it is useful to represent these structures as a string of three-dimensional Cartesian coordinates along the medial axis. This procedure was automated in order to limit the number of human interactions and to improve reproducibility. In this paper the design, implementation, and validation of the automated method is presented. From the data presented it can be concluded that the cursor algorithm provides an objective and therefore reproducible method to trace the medial axes of prophase chromosomes automatically. This method could allow a more extensive understanding of the (changes in) chromosome organisation throughout the cell cycle, its relation to cell function, and the complex process of chromosome condensation. PMID- 8354124 TI - Derivative domain fitting: a new method for resolving a mixture of normal distributions in the presence of a contaminating background. AB - Derivative domain least squares analysis is a new method for resolving multiple peaks superimposed on a slowly varying continuum into separate normal (Gaussian) distributions without developing a functional approximation for the continuum. The method is based on fitting the first derivative of the data with the first derivative of the sum of a series of normal distributions. A functional approximation for the continuum is not necessary as long as the first derivative of the continuum is approximately zero (i.e., the continuum varies slowly compared to the normal distributions). PMID- 8354125 TI - Detection of rare cells at a frequency of one per million by flow cytometry. AB - In a model study we seeded the pre-B-cell line REH into 250 million peripheral blood mononuclear cells (PBMC) at frequencies of 10(-4), 10(-5), and 10(-6). By flow cytometry we could detect the REH cells and found a background of about one event per 100 million PBMC. This sensitivity was achieved by removing four sources of false positive events, including nonspecific immunofluorescence, autofluorescence, background particles from previous experiments, and bursts of events during acquisition. To overcome limits to rare event detection imposed by nonspecific staining and autofluorescence, we used positive and negative selection for the REH cells. Another fluorochrome was added to stain the background cells and particles. In order to remove particles and background from previous experiments, a cleaning technique was developed and event bursts were removed from the analysis by developing an algorithm that screens the list-mode data for events that were not Poisson distributed. PMID- 8354126 TI - Determining Tpot in heterogeneous systems: a new approach illustrated with multicell spheroids. AB - Like many tumors, multicell spheroids from Chinese hamster V79-171b fibroblasts display karyotypic heterogeneity as they enlarge. This creates significant problems for analysis of univariate DNA content histograms of cells from spheroids, and even for bivariate bromodeoxyuridine (BrdUrd)/DNA flow histograms. While attempting to routinely measure spheroid cell kinetics with the latter approach, a simple alternative that overcomes many of the inherent problems emerged. The exit rate of BrdUrd-labelled cells from the S-phase compartment(s), determined using standard DNA analysis software, is used to define the duration of S-phase and ultimately the potential doubling time of the clonogenic cell population. This approach appears to offer several advantages over the conventional "relative movement" technique for heterogeneous samples, particularly since the subjective distinction between labelled/divided tetraploid G1 cells vs. labelled/undivided diploid G2 is no longer required. Further, the technique avoids some potential artifacts that might be expected for heterogeneous tumors where cell subpopulations proliferate with quite different cell kinetics. PMID- 8354127 TI - Comparison of pepsin and trypsin digestion on paraffin-embedded tissue preparation for DNA flow cytometry. AB - Preparation with enzymes plays an important part in obtaining good results in cellular DNA content measurements from paraffin-embedded tissue using flow cytometry. Therefore, we have compared two groups of DNA histograms obtained with pepsin (Hedley method) and trypsin digestion (Schutte method). Samples of five tumor types were compared: eight lung, seven breast, five thyroid, seven stomach, and six colon cancer cases. All samples were stained with propidium iodide (PI). The incidence of DNA aneuploidy determined by the Schutte method indicated a higher ratio in four tumor types than that determined by the Hedley method. Concerning the coefficient of variation (CV) used to estimate the quality of the DNA histogram, the diploid G1 peak determined by the Schutte method produced a smaller CV in five tumor types than did the Hedley method. This Schutte method had especially good results in lung and thyroid cancer. Furthermore, the amount of debris (background) determined by the Schutte method indicated a decrease in four tumor types compared with the Hedley method. In cell-cycle analysis of ten DNA diploid cases, DNA histograms by the Hedley method showed an increased S phase fraction due to an overlapping of debris and aggregated cells. These results indicate that preparation by trypsin digestion is a method superior to pepsin digestion when the sample from paraffin-embedded tissue is stained with PI for the purpose of DNA content measurement. PMID- 8354128 TI - Variations in DNA aneuploid cell content during tumor dissociation in human colon and head and neck cancers analyzed by flow cytometry. AB - Experimental research involving human solid tumors often requires single cell suspensions of high yield that are representative of the tissue of origin and in which the cellular property of interest is preserved. This is particularly necessary for the determination of DNA ploidy by flow cytometry. Mechanical dissaggregation and proteolytic enzyme digestion are the most commonly employed dissociation techniques for solid tumors. Comparative testing of techniques is often not performed. Mechanical and proteolytic enzyme dissociation techniques were comparatively tested in 77 human squamous cell cancers of the head and neck (SCCHN) and 25 human colon cancers for cellular yield, dye exclusion viability, quality, and morphology of DNA histograms, and the presence and proportion of DNA aneuploid subpopulations. Significant and consistent DNA aneuploid subpopulation losses were noted in mechanical preparations of SCCHN and enzymatic preparations of colon cancers. The frequency of SCCHN specimens with DNA aneuploid subpopulations was underestimated by 52% in mechanical cell suspensions, and the proportion of DNA aneuploid cells was diminished in an additional 30% of the specimens. Conversely, the frequency of specimens with DNA aneuploid subpopulations was underestimated by 38% in cell suspensions from enzymatically dissociated human colon cancer and their proportion diminished in an additional 50% of the specimens. Incubations of human colon cancers with three commonly employed proteolytic enzymes demonstrated a progressive loss of DNA aneuploid subpopulations as a function of enzyme concentration and incubation time. This is a serious potential source of error in the flow cytometric determination of DNA ploidy in human solid tumors, and may contribute to the diversity of results obtained and occasional contradictory conclusions reached in such studies. PMID- 8354129 TI - DNA ploidy status and DNA content instability within single tumors in renal cell carcinoma. AB - In order to investigate the relationship between genetic instability and DNA aneuploidy of malignant cells in human solid tumors, we studied the variations of DNA index within a single tumor. Multiple sampling (mean of 6.4 samples per tumor) was performed in 24 renal cell carcinomas (RCC). Based on the variations in DNA indices within a single tumor, RCC were divided into three groups: 1) tumors with stable DNA indices (variation within the range of the measurement error), including all DNA diploid tumors (n = 8), all hyperdiploid tumors (n = 3), a hypodiploid tumor (n = 1), and only 2 of 11 tetraploid and hypotetraploid tumors; 2) tumors with moderate variations in DNA indices, which were all close to tetraploidy (n = 5); and 3) tumors with large variations of DNA indices. In this last group, subclones present within a tumor varied widely in their DNA indices from the tetraploid to the triploid region, reflecting the DNA content instability within the tumor cell population. These results suggest that DNA aneuploidy can arise by two different mechanisms: 1) loss or gain of chromosomes leading to hypodiploid or hyperdiploid tumors with no apparent increase in DNA content instability, and 2) doubling of the chromosome set followed by random loss of chromosomes as suggested by the DNA indices ranging from tetraploid to triploid region found in three tumors. Differences in DNA indices within one tumor characterize subclones which may arise by chromosome loss or gain. PMID- 8354130 TI - Recognition and reduction of artifacts from autolysis in paraffin-embedded tissue using DNA/nuclear protein flow cytometry. AB - Artifacts from autolysis can be a problem in retrospective flow-cytometric analyses of DNA content in paraffin-embedded tissues. Autolyzed tissue from rat liver, human liver, and rat spleen were stained for DNA and nuclear protein to determine if this technique would be useful in identifying partially degraded cells. After the tissue was deparaffinized and rehydrated, the nuclei were isolated using 0.5% pepsin. Propidium iodide (PI) and fluorescein isothiocyanate (FITC) were used to stain DNA and nuclear protein. When unfixed rat liver tissue was allowed to undergo autolysis at 4 degrees C for 24-48 h before fixation, there was a progressive broadening of the G1 and G2M DNA peaks and a slight increase in the average DNA contents of these peaks. Nuclei that stained more intensely with PI also stained more intensely with FITC. Similar results were obtained using human liver and rat spleen. Sometimes the increased PI staining resulted in a false aneuploid peak. The distinctive skewing of the DNA/nuclear protein histograms from autolysis was reduced by increasing the incubation of the tissue in 0.5% pepsin from 0.5 h to 1.5 h during the nuclei-isolation step. The DNA/nuclear protein method provides a means for identifying artifacts from autolysis, whereas the extended pepsin treatment provides a means for reducing these artifacts. PMID- 8354131 TI - An improved assay for the detection of Toxoplasma gondii antibodies in human serum by flow cytometry. AB - The diagnosis of toxoplasmosis relies primarily on the demonstration of specific antibodies to Toxoplasma gondii. We describe a flow cytometry method for the determination of antibodies to whole fixed tachyzoites by indirect immunofluorescence. Fixed tachyzoites in suspension have characteristic light scattering properties. The amount of IgM, IgG, and IgA antibodies from patients' sera bound to the tachyzoites can be estimated from the mean fluorescence intensities observed using class-specific conjugates for different Ig heavy chains. Appropriate serum dilutions for the estimation of specific IgG titres and for the discrimination between sera positive and negative for IgA and IgM antibodies were established using 40 random sera from pregnant women. The method proved to be quantitative and highly sensitive as compared with currently used assays. Coefficients of variation between series ranged from 6.4% to 12.2% and could be controlled by the inclusion of positive and negative standard sera in the test series. The method might represent a major improvement in cost effectiveness as compared with routine immunofluorescence assay by fluorescent microscopy when the volume of testing is sufficient. It can be fully automated, and its large scale application is currently under investigation. PMID- 8354133 TI - Fluorescence instability of propidium iodide-labelled microspheres in (para)formaldehyde. AB - An instability of the fluorescence of propidium iodide (PI)-labelled microspheres was observed when the beads were used as an internal fluorescence standard in cell samples suspended in paraformaldehyde (pFA) for flow cytometric phenotyping. Flow cytometry of fluorochrome-labelled microspheres as well as spectrofluorometry of PI-fluorochrome solutions in PBS-buffered 1% pFA or formalin (FA) revealed strong increases of PI fluorescence starting immediately after the addition to the fixatives. We propose a chemical reaction which leads to two additional conjugated double bonds in the modified fluorochrome causing the increased fluorescence emission. Therefore, PI-labelled microspheres should not be applied as internal fluorescence references in aldehyde-containing cell suspensions for flow cytometric analysis, except when the time interval between the addition of beads and the measurement can be kept constant or if it lasts longer than 1 h. PMID- 8354132 TI - Quality control study of the Italian group of cytometry on flow cytometry cellular DNA content measurements. AB - A quality control study on DNA flow cytometry, extended to 43 national laboratories, has been carried out by the Italian Group of Cytometry, using defined fixed suspensions of cultured human leukemia K562 cells and human blood lymphocytes. The participating laboratories were allowed to follow their own staining and measurement protocols. Aliquots of cellular suspension had to be measured three times on the same day and two other times on different days. A large heterogeneity of procedures emerged among participants. The average of mean DNA index laboratory values, from 36 laboratories who sent evaluable data, was 1.68, with a range from 1.49 to 1.97. The coefficients of variation ranged from 2.35 to 9.39% and from 2.79 to 8.5% for diploid and aneuploid peaks, respectively. Statistical analysis of the results showed quite good intralaboratory reproducibility, but statistically significant differences were observed among laboratories, for both DNA indices and coefficients of variation. These differences appear to be consistent. For standardization, it is essential that efforts should be made to identify the main sources of variation and to control them. PMID- 8354134 TI - Medicines cheaper over the counter. PMID- 8354135 TI - [The prevalence of neurodermatitis among school children in the Hannover administrative district]. AB - A special questionnaire was developed to obtain up-to-date data on the prevalence of atopic dermatitis among children. It was validated by specialist diagnosis in 320 children, providing a diagnostic sensitivity and specificity of 97%. This questionnaire was used for all school entrants in 1990 in the Hanover District. A total of 4,916 children were examined and the questionnaire satisfactorily completed by a relative or guardian (usually the mother) of 4,651. The prevalence of atopic dermatitis was 11.8%, ranging from 8.4% to 17.3% among the 20 constituent communities. The regional differences were smaller than the scatter of diagnostic classifications by the school doctors and the reports of a positive history by the parents. The results demonstrate the validity of a systematic enquiry employing relevant diagnostic and anamnestic items. PMID- 8354136 TI - [A comparison of the gastroduodenal tolerance of ticlopidine and acetylsalicylic acid]. AB - Changes in the gastroduodenal mucosa caused by 250 mg ticlopidine twice daily (group 1; n = 12) or 300 mg aspirin daily (group 2; n = 12) were compared in a randomized double-blind trial of 24 healthy men, aged 20 to 35 years. An oesophago-gastroduodenoscopy was performed before and after either drug had been taken for 7 days. Results were tabulated according to a uniform scoring system (normal mucosa, erythema, petechiae, erosions, ulcer, and blood in the lumen). Both groups had identical scores at the start of the trial (group 1: 0.9 +/- 0.1; group 2: 0.8 +/- 0.1). After the seven days, the score in group 2 had risen to 9.7 +/- 1.5 (median 9.0), while it had hardly changed in group 1 (1.7 +/- 0.5; median 1.0), a statistically significant difference (P < 0.05). The data indicate that ticlopidine is better tolerated by the gastroduodenal mucosa than low dosage aspirin. PMID- 8354137 TI - [Thoracic actinomycosis masquerading as a central bronchial carcinoma]. AB - A 41-year-old cachectic woman (weight 42.7 kg, height 1.65 m) was admitted to hospital because a chest radiogram had suggested a left central bronchial carcinoma. Four days previously she had noted for the first time a firm elastic swelling parasternally in the fourth intercostal space. This swelling was directly aspirated by needle after bronchoscopic results had been nonspecific. Surprisingly, pus containing actinomyces filaments was aspirated. Computed tomography confirmed a paramediastinal abscess, 8 x 5 x 6 cm, which had infiltrated into the left thoracic wall. The abscess was incised and drained. After treatment for two weeks, initially with three times daily 10 mega penicillin G intravenously, followed by erythromycin, 500 mg twice daily for 12 weeks, the thoracic actinomycosis was no longer demonstrable radiologically and by ultrasound. It is suggested that in any unclear pulmonary infiltrate without evidence of tuberculosis or carcinoma actinomycosis should be included in the differential diagnosis. PMID- 8354138 TI - [Biliary complications following laparoscopic cholecystectomy. Endoscopic retrograde cholangiopancreatography in the diagnosis and therapy]. PMID- 8354139 TI - [Cushing syndrome. III: Cortisol or glucocorticoid excess]. PMID- 8354140 TI - [Stepwise diagnosis in oropharyngeal dysphagia and functional disorders of the pharyngoesophageal segment]. PMID- 8354141 TI - [Helicobacter pylori infection and ulcer disease]. PMID- 8354142 TI - [Oxyuriasis]. PMID- 8354143 TI - [Oral hygiene in the critically ill]. PMID- 8354144 TI - [An accelerated appearance of a multifocal leukoencephalopathy caused by fluorouracil and ranitidine]. PMID- 8354145 TI - [Obstructive jaundice caused by a metal clip in the common bile duct following laparoscopic cholecystectomy]. PMID- 8354147 TI - [Blood pressure development in children and youth. Observation of its course in children over 10 years]. AB - 115 children (79 boys, 36 girls; mean age 11 4/12 [10 1/2-15 4/12] years) with primary borderline blood pressure or mild hypertension (90th to 97th percentile according to the German League for the Fight Against High Blood Pressure) and 115 healthy children of corresponding age (52 boys and 63 girls) with innocent cardiac murmurs were followed in a paediatric cardiologic outpatient department, initially for 5 years. Blood pressure was measured at rest and on exercise (bicycle ergometry). After 5 years 51 of the children with primary hypertension (44%) still had borderline pressures, in 11 moderately severe hypertension had developed, while in the remaining 53 children (46%) the blood pressure was normal. Among the control group borderline pressures were recorded in only two children. After 10 years, 92 children in the test group and 79 in the control group were re-examined. 26 children (28%) among the test group were normotensive, 35 (38%) had borderline pressures, and 31 (34%) had moderately severe hypertension. Among the control group, borderline hypertension had developed in 3 children, moderate hypertension in one. Among children with persisting hypertension those with hypertension on exercise and/or over-weight significantly predominated (85% and 66%, respectively). PMID- 8354146 TI - [Acute effect of metoclopramide on esophagus motility in diabetes mellitus]. AB - The acute effect of metoclopramide on oesophageal motility was investigated prospectively in 33 consecutive patients (20 men and 13 women; mean age 60.5 +/- 12.6 years) with type I (n = 8) or type II (n = 25) diabetes. 15 patients had a peripheral sensory-motor polyneuropathy only and three just an autonomic cardial neuropathy. Both lesions were present in ten, none in five. No patient had oesophago-gastroduodenal lesions. Sphincter pressure, relaxation time, contraction amplitude and propulsion velocity of bolus-induced oesophageal peristalsis were measured manometrically after intravenous administration of 10 mg metoclopramide. Resting pressure in the lower oesophageal sphincter rose significantly by 26.7%, contraction amplitude in the tubular portion of the oesophagus by more than 30%, and propulsion velocity by more than 20% (P for each < 0.05). At the same time the amount of segmental and aperistaltic oesophageal contractions regressed significantly. The effect of metoclopramide was demonstrated regardless of the type of diabetes, duration of diabetes and any manifestation of autonomic cardial or peripheral sensory-motor neuropathy. PMID- 8354148 TI - [Glucocorticoid monotherapy for Cogan syndrome?]. AB - A 27-year-old woman suddenly developed persistent rotatory dizziness with unsteadiness on standing and walking, associated with symptoms relating to the autonomic nervous system, all signs and symptoms disappearing without treatment in 3 days. Ten days before this episode she had noticed progressive bilateral impairment of hearing accompanied by tinnitus. Caloric and audiometric tests confirmed bilateral impairment of the audiovestibular organ. A week later she also developed bilateral iritis and papillitis. The constellation of ocular and audiovestibular signs suggested Cogan's syndrome. Under high-dosage glucocorticoid treatment (initially 1,000 mg/d prednisolone intravenously for 3 days, then 100 mg/d orally in decreasing doses down to 10 mg daily) the ocular signs improved, but the bilateral hearing impairment persisted. A recurrence occurred after 5 months, while on a prednisolone dosage of 10 mg daily, together for the first time with arthralgias, suggesting systemic involvement. Although the symptoms quickly subsided when dosage was increased to 100 mg daily, repeated attempts at dose reduction brought about renewed exacerbation at 70 mg daily. As the necessary high steroid dosage led to severe side effects, an immunosuppressive drug was added (100 mg cyclophosphamide and 20 mg prednisolone, both daily; later 5 mg methotrexate weekly and 4 mg prednisolone every other day). The symptoms had not recurred when re-examined 7 months later. PMID- 8354149 TI - [Atrial septum aneurysm as the cause of a thromboembolic infarction of the brain stem and cerebellum?]. AB - A 32-year-old woman with migraine for several years again had a migraine attack with headache, nausea, vomiting and eye-muscle disorder, 14 days after an uncomplicated delivery. Within 24 hours a left-dominant hemiparesis developed, followed 12 hours later by tonic-clonic seizure and deep unconsciousness (Glasgow score: 3); the patient could not be aroused. Cranial computed tomography revealed extensive infarction of the brainstem and cerebellum. Angiography demonstrated occlusion of the basilar artery but not other abnormalities of other vessels. There was no evidence for vascular anomalies and the clotting tests were normal. Transoesophageal echocardiography demonstrated an atrial septal aneurysm. But any interatrial shunt (e.g. through a patent foramen ovale) was excluded by colour Doppler sonography, making it highly unlikely that a paradoxical embolus was the cause of the infarction. The brainstem infarction resulting from the basilar artery occlusion did not respond to treatment and the patient died 10 days after the initial seizure. PMID- 8354150 TI - [Therapeutic possibilities for shoulder arthroscopy]. PMID- 8354151 TI - [Cardioembolic stroke]. PMID- 8354152 TI - [Are results from animal experiments applicable to humans?]. PMID- 8354153 TI - [Sudden visual and speech disorder]. PMID- 8354154 TI - [Resistance to diuretics in congestive heart insufficiency]. PMID- 8354155 TI - The electro-auditory physiology frontier. PMID- 8354156 TI - Clinical correlates of sudden auditory-vestibular loss in a cochlear implant patient. AB - The precise electrophysiologic mechanism for sudden sensorineural auditory vestibular loss has yet to be defined. No human models exist for this idiopathic phenomenon. A 67-year-old cochlear implant (CI) patient experienced what could be termed a "typical" acute sudden auditory-vestibular loss. Vestibular and CI electrical psychophysical changes were monitored over a 22-month period. Once the acute vestibular problems diminished, CI electrical parameters returned to near pre-episode levels. Some improvement occurred in rotational chair phase lag and asymmetry. While improving, platform posturography continued to show difficulty performing sensory organization tests V and VI. These clinical findings may imply that ganglion cell and neuronal population are responsible for the auditory findings in sudden auditory-vestibular loss. Secondly, a CI patient may serve as an ideal human model for further study of this phenomenon, should it occur. PMID- 8354157 TI - Aggressive fibromatosis (fibrosarcoma) of the facial nerve. AB - Aggressive fibromatosis of the facial nerve is a very rare tumor. Three cases have been previously reported. The tumor is locally recurrent and often has a fatal outcome. This report is of a ten-year-old boy whose tumor originally developed in the parotid area with subsequent spread to the base of the skull, the neck and the cerebellopontine angle. Treatment was by wide surgical excision, radiation therapy and chemotherapy. Despite treatment, the patient died. The clinical features of this case will be described. Only wide surgical excision early in the course of the disease may offer a chance for cure. PMID- 8354158 TI - Aneurysms of the temporal bone. AB - Aneurysms of the internal carotid artery in the temporal bone are rare lesions which can present clinically as a growth in the middle ear cleft. Hemorrhage, occurring spontaneously or iatrogenically, is a primary concern. This study describes morphological and embryological characteristics of the internal carotid artery in relationship to the protympanum and temporal bone. Concepts of pathogenesis and pathology are discussed, with reference to the neurosurgical and otolaryngologic literature. Clinical characteristics, including methods of surgical repair, are presented using three illustrative case reports. Methods of surgical repair include: 1) reinforcement; 2) ligation; and 3) primary excision and reanastomosis. PMID- 8354160 TI - Viral otitis media. PMID- 8354159 TI - Is fine needle aspiration biopsy of salivary gland masses really necessary? AB - The use of fine needle aspirate biopsies (FNAB's) in the outpatient setting has progressively escalated, particularly in the area of head and neck pathology. An increasing percentage of these are for salivary gland masses. We present our experience with salivary gland FNAB's at our institution for four years, from 1988-1992. One thousand and twenty-two (1,022) FNAB's of superficial masses were performed by two pathologists. One hundred sixty-three (15.9%) were salivary gland biopsies. Of these 163 cases, 21 (12.9%) were normal tissue, 77 (47.2%) were inflammatory processes, 50 (30.7%) were benign tumors, and 15 (9.2%) were malignant tumors. None of the aspirates were unsatisfactory. Tissue correlation was possible in 47 (28.8%) cases. Two false negative cases (4.3%) were identified; these were a Warthin's tumor diagnosed as chronic sialoadenitis by FNAB; and a poorly differentiated squamous cell carcinoma diagnosed as adenocarcinoma by FNAB. There were no false positive cases. Overall sensitivity was 95.7% and specificity was 100%. Our experience indicates that FNAB of salivary glands is an effective screening procedure in evaluating salivary gland masses. The cytologic diagnosis may assist the clinician in allaying patients' anxieties, as well as in further collateral workup prior to definitive therapy. PMID- 8354161 TI - Endoscopic view of ostium of nasolacrimal duct. PMID- 8354162 TI - Hemorrhagic polyp. PMID- 8354163 TI - Twenty years of environmental health research. A dedication to David P. Rall. PMID- 8354164 TI - Twenty years of environmental health research. A dedication to David P. Rall. Introduction. PMID- 8354165 TI - Advances in mechanisms of activation and deactivation of environmental chemicals. AB - Environmental chemicals are both activated and detoxified by phase I and phase II enzymes. The principal enzymes involved in phase I reactions are the cytochrome P 450s. The phase II enzymes include hydrolase and the conjugative enzymes such as glucuronyltransferases, glutathione transferases, N-acetyltransferase, and sulfotransferase. Although other phase I and phase II enzymes exist, the present review is limited to these enzymes. Once thought to be a single enzyme, multiple cytochrome P-450 enzymes have been purified and characterized from many different species across the evolutionary tree. The application of molecular biology techniques to this field has identified more than 150 cytochrome P-450 genes to date. At least 20-30 cytochrome P-450 enzymes appear to exist in each mammalian species, and many polymorphisms in these enzymes are being identified. The cytochrome P-450 enzymes can now be expressed in recombinant form using cDNA expression systems. The phase II conjugative enzymes add a hydrophilic moiety such as sulfate, glucuronide, or acetate to compounds, which increases their water solubility and facilitates their excretion. However, conjugates of a number of compounds also result in more reactive electrophilic species, which appear to be the ultimate carcinogens. Many of these phase II enzymes also represent families of enzymes, and polymorphisms can affect the ability of these enzymes to metabolize chemicals. Whenever possible, we have reviewed knowledge of the human enzymes involved in particular pathways. PMID- 8354166 TI - Lead toxicity: current concerns. AB - Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium mediated control of vascular smooth muscle contraction and on the renin angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. PMID- 8354167 TI - Chemicals and cancer in humans: first evidence in experimental animals. AB - Certain human diseases have been traced to exposure to environmental and occupational chemicals. In many instances the first evidence of potential adverse effects came from experimental studies and were subsequently discovered in humans. Associations of human cancers, as a diverse group of diseases, and chemicals have been made since the middle 1700s. Since then, nearly 100 chemicals, mixtures of chemicals, or exposure circumstances are now recognized as being or strongly implicated as being carcinogenic to humans. Of the less than 1000 agents evaluated adequately for carcinogenicity in laboratory animals, a varying spectrum of data from studies on humans are available for only about 20 25%. So far, more than 60 agents are linked unequivocally as causing cancer in humans, and another 50 or so are strongly suspected of being carcinogenic to humans. Not all of these have been or can be evaluated in animals because some are industrial processes or "occupations," some are environmental and cultural risk factors, and some are mixtures of agents. For those that can be studied experimentally, the qualitative concordance between humans and animals approaches unity, and in every case there is at least one common organ site of cancer in both species. The evidence of carcinogenicity in experimental animals preceded that observed in humans for nearly 30 agents and is the subject of this paper. PMID- 8354168 TI - Asbestos-induced lung disease. AB - This review attempts to deal with two major questions concerning asbestos-induced lung disease: How does inhaled asbestos cause cell proliferation and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the past 10 years, and there appear to be two hypothetical schemes which could explain, at least in part, the fibroproliferative effects of asbestos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first, but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple varieties of growth factors and cytokines that mediate the pathogenesis of asbestosis. There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor beta, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos induced fibrosis. The challenge today is to establish which combinations of the many factors released actually are playing a role in disease pathogenesis. The issue of continued risk currently is more a question of policy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances under which asbestos in buildings constitutes an ongoing health hazard. The litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a complete carcinogen. It appears to be generally nongenotoxic, but all asbestos fiber types can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation. PMID- 8354169 TI - Complex mixtures of air pollutants: characterizing the cancer risk of polycyclic organic matter. AB - Complex mixtures of polycyclic organic matter (POM) are used to illustrate the scientific problems and issues associated with characterizing the comparative risk of related complex mixtures. The complexity of mixtures in which the active components are not well characterized present special challenges, which include identifying the critical components of mixtures, their sources, and the appropriate biomarker(s) of exposure and dose; developing the appropriate experimental models for dose-response assessment; species extrapolation; and developing a scientific basis for predicting from one mixture to another. Strategies for addressing these issues include bioassay-directed chemical characterization of bioactive components of complex mixtures, apportionment methods to determine the source of biological activity and risk, DNA adduct methods to determine tissue exposure and target dose of mixtures, and comparative approaches to determining the relative similarity, potency, and risk of complex mixtures. Epidemiological data are available for humans exposed to POM from coke ovens, coal roofing tar, coal smoke, aluminum smelters, and cigarette smoke. These emissions are characterized and compared to POM from automotive emissions (diesel and gasoline), woodstove emissions, residential oil furnace emissions, and ambient air particles. The tumor potency and estimated cancer risks for these POM mixtures ranges over nearly three orders of magnitude. PMID- 8354170 TI - Chemical agents and the immune response. AB - Our desire to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals has increased, in part, due to the fact that chemical companies are moving to larger and/or different markets. It has been estimated that 35 million Americans suffer from allergic disease, of which 2-5% are from occupational exposure. Although there is not yet a clear understanding of dose response relationships or disease predisposition, there are many well-defined examples (isocyanates, anhydrides) of chemical sensitizers in humans and experimental animals. Evidence that chemicals suppress immune responses in humans is considerably less well established, although there is a public perception that chemicals generally cause immunosuppression. This perception has been fueled by highly publicized legal cases and scientific controversies within the academic and industrial communities. As a consequence of these public and scientific concerns, many of the regulatory agencies are developing immunotoxicity testing guidelines. At the present, however, there are limitations on adequate human methodology and data that allow the extrapolation of animal data to assess human risk. The potential for human immunosuppression remains of concern, however, because of a large database generated from animal studies that demonstrates immunosuppression as well as reports of immunosuppression in humans inadvertently (e.g., halogenated aromatic hydrocarbons) or occupationally (asbestos, benzene) exposed to xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354171 TI - Carcinogenicity of 1,3-butadiene. AB - 1,3-Butadiene, a high-production volume chemical used largely in the manufacture of synthetic rubber, is a multiple organ carcinogen in rats and mice. In inhalation studies conducted in mice by the National Toxicology Program, high rates of early lethal lymphomas occurring at exposure levels of 625 ppm or higher reduced the development and expression of later developing tumors at other sites. Use of survival-adjusted tumor rates to account for competing risk factors provided a clearer indication of the dose responses for 1,3-butadiene-induced neoplasms. An increase in lung tumors in female mice was observed at exposure concentrations as low as 6.25 ppm, the lowest concentration ever used in a long term carcinogenicity study of this gas. Human exposures to 1,3-butadiene by workers employed at facilities that produce this chemical and at facilities that produce styrene-butadiene rubber have been measured at levels higher than those that cause cancer in animals. Furthermore, epidemiology studies have consistently revealed associations between occupational exposure to 1,3-butadiene and excess mortality due to lymphatic and hematopoietic cancers. In response to the carcinogenicity findings for 1,3-butadiene in animals and in humans, the Occupational Safety and Health Administration has proposed lowering the occupational exposure standard for this chemical from 1000 ppm to 2 ppm. Future work is needed to understand the mechanisms of tumor induction by 1,3-butadiene; however, the pursuit of this research should not delay the reduction of human exposure to this chemical. PMID- 8354172 TI - Contamination and restoration of groundwater aquifers. AB - Humans are exposed to chemicals in contaminated groundwaters that are used as sources of drinking water. Chemicals contaminate groundwater resources as a result of waste disposal methods for toxic chemicals, overuse of agricultural chemicals, and leakage of chemicals into the subsurface from buried tanks used to hold fluid chemicals and fuels. In the process, both the solid portions of the subsurface and the groundwaters that flow through these porous structures have become contaminated. Restoring these aquifers and minimizing human exposure to the parent chemicals and their degradation products will require the identification of suitable biomarkers of human exposure; better understandings of how exposure can be related to disease outcome; better understandings of mechanisms of transport of pollutants in the heterogeneous structures of the subsurface; and field testing and evaluation of methods proposed to restore and cleanup contaminated aquifers. In this review, progress in these many different but related activities is presented. PMID- 8354173 TI - Aquatic toxicology: past, present, and prospects. AB - Aquatic organisms have played important roles as early warning and monitoring systems for pollutant burdens in our environment. However, they have significant potential to do even more, just as they have in basic biology where preparations like the squid axon have been essential tools in establishing physiological and biochemical mechanisms. This review provides a brief summary of the history of aquatic toxicology, focusing on the nature of aquatic contaminants, the levels of contamination in our waters, and the origins of these agents. It considers the features of the aquatic environment that determine the availability of xenobiotics to aquatic life and the fate of foreign chemicals within the organism. Finally, toxic effects are considered with primary emphasis on the potential of aquatic models to facilitate identification of the underlying mechanisms of toxicity. PMID- 8354175 TI - Developmental toxicology: status of the field and contribution of the National Toxicology Program. AB - The NTP has conducted developmental toxicity studies on more than 50 chemicals, often in multiple species. Several chemicals caused developmental toxicity in the absence of any toxicity to the mother. Although hazard to humans is determined by the level of exposure to the chemical and its inherent toxicity, those agents that selectively disturb the development of the conceptus are of particular concern because other manifestations of toxicity would not warn the mother of overexposure. Whether the LOAEL (lowest-observed adverse effect level) for maternal toxicity was high or low did not correlate with the potential of chemicals to cause developmental toxicity. The form of developmental toxicity that determined the LOAEL most frequently was decreased body weight in mice and rats, but not rabbits, where the LOAEL was determined more often by an increase in resorptions. Several in vitro and short-term tests appear promising as screens to predict the outcome of developmental toxicity studies in mammals. However, the only screens that have undergone formal validation studies are those evaluated by the NTP. Improvements in our ability to predict risk to humans have been limited by our knowledge of the mechanisms by which agents cause developmental toxicity. Thus, future growth is dependent on a better understanding of the biological processes that regulate normal development, therein providing the necessary framework for understanding mechanisms of abnormal development. PMID- 8354174 TI - Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems. AB - Polychlorinated biphenyls (PCBs) are industrial compounds that have been detected as contaminants in almost every component of the global ecosystem including the air, water, sediments, fish, and wildlife and human adipose tissue, milk, and serum. PCBs in commercial products and environmental extracts are complex mixtures of isomers and congeners that can now be analyzed on a congener-specific basis using high-resolution gas chromatographic analysis. PCBs are metabolized primarily via mixed-function oxidases into a broad spectrum of metabolites. The results indicate that metabolic activation is not required for PCB toxicity, and the parent hydrocarbons are responsible for most of the biochemical and toxic responses elicited by these compounds. Some of these responses include developmental and reproductive toxicity, dermal toxicity, endocrine effects, hepatotoxicity, carcinogenesis, and the induction of diverse phase I and phase II drug-metabolizing enzymes. Many of the effects observed for the commercial PCBs are similar to those reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Structure-function relationships for PCB congeners have identified two major structural classes of PCBs that elicit "TCDD-like" responses, namely, the coplanar PCBs (e.g., 3,3',4,4'-tetraCB, 3,3'4,4',5-pentaCB and 3,3',4,4',5,5'-hexaCB) and their mono-ortho coplanar derivatives. These compounds competitively bind to the TCDD or aryl hydrocarbon (Ah) receptor and exhibit Ah receptor agonist activity. In addition, other structural classes of PCBs elicit biochemical and toxic responses that are not mediated through the Ah receptor. The shor-term effects of PCBs on occupationally exposed humans appear to be reversible, and no consistent changes in overall mortality and cancer mortality have been reported. Recent studies have demonstrated that some developmental deficits in infants and children correlated with in utero exposure to PCBs; however, the etiologic agent(s) or structural class of PCBs responsible for these effects have not been delineated. In contrast, based on a toxic equivalency factor approach, the reproductive and developmental problems in certain wildlife populations appear to be related to the TCDD-like PCB congeners. PMID- 8354176 TI - Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells. AB - Because genetically based diseases have a major impact on human health, the National Institute of Environmental Health Sciences (NIEHS) has conducted a research and testing program for more than a decade to address chemical induction of heritable genetic damage in the germ cells of mammals. Although most genetic disease results from preexisting mutations, a portion is due to the occurrence of new mutations. The supposition that exposure to mutagenic chemicals contributes to the occurrence of new mutations in the human population is strongly supported by the results from animal models. Such studies clearly demonstrate the potential of environmental chemicals to induce mutations in both somatic and reproductive cells of mammals. This NIEHS program has become a leader in the identification of genetic hazards in the environment and in the acquisition of animal model data used by regulatory agencies in assessing genetic risks to human health. PMID- 8354178 TI - Genetic toxicology: current status of methods of carcinogen identification. AB - A critical aspect of the efforts to relate the results of short-term genetic toxicity tests with those from long-term rodent tests for carcinogens is the quality and consistency of the studies conducted by the National Toxicology Program. Analysis of the results in relationship to chemical structure has shown that mutagenic potential is a primary risk factor for carcinogen identification. Chemicals positive in the Salmonella assay-generally possess "structural alerts" for electrophilic interactions, are predominantly represented among chemicals producing trans-species carcinogenic effects in rodents, and among those identified as carcinogenic to humans. Current efforts are aimed at defining toxicological, structural, and mechanistic properties of nonmutagens that are carcinogenic in rodents. PMID- 8354177 TI - The toxicology of benzene. AB - Benzene is metabolized, primarily in the liver, to a series of phenolic and ring opened products and their conjugates. The mechanism of benzene-induced aplastic anemia appears to involve the concerted action of several metabolites acting together on early stem and progenitor cells, as well as on early blast cells, such as pronormoblasts and normoblasts to inhibit maturation and amplification. Benzene metabolites also inhibit the function of microenvironmental stromal cells necessary to support the growth of differentiating and maturing marrow cells. The mechanism of benzene-induced leukemogenesis is less well understood. Benzene and its metabolites do not function well as mutagens but are highly clastogenic, producing chromosome aberrations, sister chromatid exchange, and micronuclei. Benzene has been shown to be a multi-organ carcinogen in animals. Epidemiological studies demonstrate that benzene is a human leukemogen. There is need to better define the lower end of the dose-response curve for benzene as a human leukemogen. The application of emerging methods in biologically based risk assessment employing pharmacokinetic and mechanistic data may help to clarify the uncertainties in low-dose risk assessment. PMID- 8354179 TI - Mercury: major issues in environmental health. AB - In the past, methylmercury compounds were manufactured as fungicides or appeared as unwanted byproducts of the chemical industry, but today the methylation of inorganic mercury in aquatic sediments and soils is the predominant if not the sole source of methylmercury. This form of mercury is bioaccumulated to a high degree in aquatic food chains to attain its highest concentrations in edible tissues in long-lived predatory fish living in both fresh and ocean waters. It is well absorbed from the diet and distributes within a few days to all tissues in the body. It crosses without hindrance the blood-brain and placental barriers to reach its principal target tissue, the brain. It is eliminated chiefly in the feces after conversion to inorganic mercury. The biological half-time of methylmercury in human tissues is about 50 days, but there is wide individual variation. Adult poisoning is characterized by focal damage to discrete anatomical areas of the brain such as the visual cortex and granule layer of the cerebellum. A latent period of weeks or months may ensue before the appearance of signs and symptoms of poisoning. The latter manifest themselves as paresthesia, ataxia, constriction of the visual fields, and hearing loss. The prenatal period is the most sensitive stage of the life cycle to methylmercury. Prenatally poisoned infants exhibit a range of effects from severe cerebral palsy to subtle developmental delays. Methylmercury is believed to inhibit those processes in the brain specially involved in development and growth such as neuronal cell division and migration. PMID- 8354180 TI - Agricultural exposures and cancer trends in developed countries. AB - Recent increases have been reported in industrial countries for several sites of cancer. The causes of these increases remain unknown. Efforts should proceed to identify those occupational groups with increases in the same sites, as these may indicate relevant exposures. Two analyses were undertaken: trends in cancer mortality in industrial countries were reviewed to identify recently increasing sites and summaries were compiled of studies on farmers which have shown increased risks for these same sites of cancer. Using data provided by the World Health Organization, age-specific rates were developed for a number of sites of cancer from 1968 to 1986. Trends in the ratio of male to female cancer mortality were also assessed for several of these countries. Based on a literature review by the National Cancer Institute, patterns of cancer in farmers reported in 20 studies from 8 countries are summarized, weighting each study by its size to create combined relative risks. In industrial countries, rates of cancer mortality increased for a number of sites, including melanoma, prostate, non Hodgkin's lymphoma, multiple myeloma, breast, brain, and kidney cancer. The ratio of male to female cancer mortality (for all sites of cancer excluding lung) has generally increased in several countries during this same time period. Many of the same sites that have increased in the general population have also been found to be increasing in farmers. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain in many surveys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354182 TI - Mechanisms of kidney cell injury from metals. AB - The most environmentally abundant toxic metals/metalloids (arsenic, cadmium, lead, and mercury) are each known to produce cell injury in the kidney but the molecular mechanisms underlying these events are now being elucidated. It is clear that the nephrotoxicity of these agents is due, in part, to the fact that urinary elimination is a major route of excretion from the body. The role(s) of molecular factors such as metal-binding proteins, inclusion bodies, and cell specific receptorlike proteins that appear to influence renal tubule cell expression, have attracted increased interest as determinants that modulate cell populations as special risk for toxicity and renal cancer. The future of mechanistic toxicology studies with regard to how and why only certain renal cell populations become targets for toxicity from these metals/metalloids and other less common inorganic nephrotoxicants must focus on the molecular handling of these agents by target cell populations. PMID- 8354181 TI - Human health effects of air pollution. AB - Over the past three or four decades, there have been important advances in the understanding of the actions, exposure-response characteristics, and mechanisms of action of many common air pollutants. A multidisciplinary approach using epidemiology, animal toxicology, and controlled human exposure studies has contributed to the database. This review will emphasize studies of humans but will also draw on findings from the other disciplines. Air pollutants have been shown to cause responses ranging from reversible changes in respiratory symptoms and lung function, changes in airway reactivity and inflammation, structural remodeling of pulmonary airways, and impairment of pulmonary host defenses, to increased respiratory morbidity and mortality. Quantitative and qualitative understanding of the effects of a small group of air pollutants has advanced considerably, but the understanding is by no means complete, and the breadth of effects of all air pollutants is only partially understood. PMID- 8354183 TI - The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989. AB - This paper is the fifth plot of the Carcinogenic Potency Database (CPDB) that first appeared in this journal in 1984 (1-5). We report here results of carcinogenesis bioassays published in the general literature between January 1987 and December 1988, and in technical reports of the National Toxicology Program between July 1987 and December 1989. This supplement includes results of 412 long term, chronic experiments of 147 test compounds and reports the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,5,6) for a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The five plots of the database are to be used together, as results of individual experiments that were published earlier are not repeated. In all, the five plots include results of 4487 experiments on 1136 chemicals. Several analyses based on the CPDB that were published earlier are described briefly, and updated results based on all five plots are given for the following earlier analyses: the most potent TD50 value by species, reproducibility of bioassay results, positivity rates, and prediction between species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354185 TI - Risk assessment: the perspective and experience of U.S. environmentalists. AB - Risk assessment is a set of decision rules widely used in the United States for identifying and quantifying the risks of chemicals and other events for adverse effects to human health, usually cancer. Scientific criticism has been directed toward the default assumptions and test methods used in risk assessment by regulatory agencies. This paper evaluates the contribution of risk assessment as an instrument of public policy toward the timely and efficient resolution of controversial issues in environmental and occupational health. Experience with risk assessment during the past decade does not support its utility in this regard. Alternatives to risk assessment in its current formulation are discussed. PMID- 8354186 TI - A second look at methanol. PMID- 8354184 TI - Mechanisms of multistep carcinogenesis and carcinogen risk assessment. AB - Many different types of chemical exposures can increase the incidence of tumors in animals and humans, but usually a long period of time is required before the carcinogenic risk of an exposure is manifested. Both of these observations can be explained by a multistep/multigene model of carcinogenesis. In this model, a normal cell evolves into a cancer cell as the result of heritable changes in multiple, independent genes. The two-stage model of initiation and promotion for chemical carcinogenesis has provided a paradigm by which chemicals can act by qualitatively different mechanisms, but the process of carcinogenesis is now recognized as more complex than simply initiation and promotion. Even a three stage model of initiation, promotion, and progression, which can be operationally defined, is not adequate to describe the carcinogenic process. The number of genes altered in a cancer cell compared to a normal cell is not known; recent evidence suggests that 3-10 genetic events are involved in common adult malignancies in humans. Two distinct classes of genes, protooncogenes and tumor suppressor genes, are involved in the cancer process. Multiple oncogenes may be activated in a tumor, while multiple tumor-suppressor genes may be inactivated. Identification of the genes involved in carcinogenesis and elucidation of the mechanisms of their activation or inactivation allows a better understanding of how chemical carcinogens influence the process of neoplastic evolution. The findings of multiple genetic changes (including point mutations, chromosomal translocations, deletions, gene amplification, and numerical chromosome changes) in activated protooncogenes and inactivated tumor-suppressor genes provide experimental support for Boveri's somatic mutation theory of carcinogenesis. In addition to mutagenic mechanisms, chemicals may heritably alter cells by epigenetic mechanisms and enhance the clonal expansion of altered cells. Most chemical carcinogens operate via a combination of mechanisms, and even their primary mechanism of action may vary depending on the target tissues. The classification of chemicals by mechanism of action or by nongenotoxic or genotoxic activity has certain inherent difficulties because no classification of chemicals is exhaustive or definitive. PMID- 8354187 TI - Banking on future research. PMID- 8354188 TI - Cleaner air may mean worse health. PMID- 8354189 TI - Women's health research at NIEHS. PMID- 8354190 TI - Environmentally related cancer in women. PMID- 8354191 TI - Diethylstilbestrol as a model for environmental estrogens. PMID- 8354193 TI - NIEHS to play unique role in women's health research effort. PMID- 8354192 TI - Role of the environment in osteoporosis. PMID- 8354194 TI - Minority health research. PMID- 8354195 TI - A holistic approach to breast cancer research. PMID- 8354196 TI - What's good for the gander may not be good for the goose. PMID- 8354197 TI - Monitoring nitrite, N-nitrosodiethanolamine, and mutagenicity in cutting fluids used in the metal industry. AB - We carried out an integrated environmental/biological monitoring program to evaluate cancer hazards among metal industry workers exposed to cutting fluids. Several cutting fluids were sampled according to response to a semiquantitative nitrite rapid test in metal factories in central Italy. The nitrite-positive samples were analyzed for nitrite and nitrosodiethanolamine (NDELA) content and mutagenic activity. The nitrite-negative samples were analyzed only for mutagenicity. Of the total samples, 20.6% were nitrite positive, and all contained NDELA. However, nitrite content was not quantitatively predictive of the NDELA content, which varied enormously among samples (0.3-1900 mg/kg). Nitrite-negative samples were always nonmutagenic. Mutagenicity was found in half the NDELA-containing samples but was not related to nitrite or NDELA content. Nitrite screening of cutting fluids in the field is an interesting method for identifying samples that potentially contain NDELA and other unknown mutagens and, when performed with short-term mutagenicity tests, nitrite screening seems to be a valid tool by which industrial managers and health officers could minimize the health hazards associated with occupational exposure to cutting fluids. PMID- 8354198 TI - Characterization of acute 4,4'-methylene dianiline hepatotoxicity in the rat. AB - Methylene dianiline (DDM) is a chemical intermediate in the production of isocyanates and other industrial chemicals, and it is hepatotoxic in humans. The acute hepatotoxicity of orally administered DDM was characterized in rats. Rats receiving DDM (25-225 mg/kg, per os) demonstrated a dose-dependent elevation in serum alanine aminotransferase activity, g-glutamyltransferase activity, and serum bilirubin concentration. DDM also caused a decrease in bile flow and an elevation in liver weight. Significant changes in these markers of liver injury occurred between 8 and 12 hr after a single, oral administration of DDM. Histologically, DDM caused multifocal, necrotizing hepatitis with neutrophil infiltration. Changes in the portal regions consisted of bile ductular necrosis, portal edema, neutrophil infiltration, mild fibrin exudation, and segmental necrotizing vasculitis. The role of cytochrome P450 monooxygenase (MO)-mediated metabolism in DDM hepatotoxicity was evaluated using the MO inhibitors, aminobenzotriazole and SKF-525A and the MO inducers phenobarbital and beta naphthoflavone. Aminobenzotriazole provided protection from DDM-induced hepatotoxicity, whereas SKF-525A had no effect. The effect of phenobarbital pretreatment depended on the dose of DDM administered. At a dose of DDM that produced a maximal hepatotoxic response, phenobarbital did not influence hepatotoxicity. However, phenobarbital pretreatment provided protection against the hepatotoxic effects of a lower dose of DDM. beta-naphthoflavone pretreatment had a more modest effect on DDM-induced hepatic insult. These results demonstrate that DDM causes acute hepatotoxicity in the rat that is dose and time dependent. Results using inducers and inhibitors of MO suggest that DDM requires bioactivation to exert toxicity; however, the relationship between metabolism and toxicity may be complex. PMID- 8354199 TI - Evaluation of the biological effects of police radar RAMER 7F. AB - This paper presents results of experiments on the effects of electromagnetic radiation in the millimeter range (frequency 34.0 +/- 0.1 GHz, power density 20 muW/cm2) emitted by a police radar device. Considering the physical properties of the radiation in millimeter range (skin effects), the experiments were carried out on hairless mice. The main physiological parameters tested were body mass, body temperature, peripheral blood, and mass and cellularity of several important organs. Critical organs, the skin, and cornea were examined by electron microscopy. Differentiation ability of hematopoietic cells, progenitors of granulocytes and macrophages, and DNA synthesis in the cornea were compared in irradiated and nonirradiated animals. None of the parameters tested was affected to an extent that would indicate the start of a pathological process or the risk of damage to genetic material. PMID- 8354200 TI - Nasal cytology in southwest metropolitan Mexico City inhabitants: a pilot intervention study. AB - Southwest metropolitan Mexico City (SWMMC) inhabitants have been exposed several hours per day for the last 6 years to photochemical smog, ozone being the most important oxidant pollutant. Subjects exposed to the SWMMC atmosphere develop several histopathological changes in their nasal mucosa: dysplasia is the most significant, affecting 78.72% of adult individuals within 60 or more days of residence in SWMMC. This study was originally designed to explore whether chemical intervention could modify nasal dysplasia, as determined by nasal cytology, in a defined adult population. In a placebo-controlled, randomized, double-blind trial, 177 healthy male subjects were divided into 5 groups to whom 5000 IU of vitamin A, 100 IU of vitamin E, a combination of vitamins A and E (5000 IU + 100 IU), 16 mg of beta-carotene, or placebo were administered daily for 4 months. Sixteen clinical and cytological variables were monitored. No effect on dysplasia was seen at the end of the 4-month trial; however, an apparent reversibility as well as progression of the dysplastic nasal lesions and high correlation coefficients between dysplasia and nasal cytology of polymorphonuclear leukocytes (PMNs; 0.85), squamous metaplasia (SM; 0.50), and nasal mucosa atrophy (NMA; 0.41) were found. A mathematical theoretical nasal dysplasia (tD) predictor equation for SWMMC adult male inhabitants is proposed (tD = 0.85 delta PMNs + 0.50 delta SM + 0.41 delta NMA + 0.98), in which PMNs are the best single dysplasia predictor, and all variables are independent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354201 TI - Bacterial and human cell mutagenicity study of some C18H10 cyclopenta-fused polycyclic aromatic hydrocarbons associated with fossil fuels combustion. AB - A number of isomeric C18H10 polycyclic aromatic hydrocarbons (PAHs), thought to be primarily cyclopenta-fused PAHs, are produced during the combustion and pyrolysis of fossil fuels. To determine the importance of their contributions to the total mutagenic activity of combustion and pyrolysis samples in which they are found, we characterized reference quantities of four C18H10 CP-PAHs: benzo[ghi]fluoranthene (BF), cyclopenta[cd]pyrene (CPP), cyclopent[hi]acephenanthrylene (CPAP), and cyclopent[hi]aceanthrylene (CPAA). Synthesis of CPAA and CPAP is described. The availability of reference samples of these isomers also proved to be an essential aid in the identification of the C18H10 species often found in combustion and pyrolysis samples. Chemical analysis of selected combustion and pyrolysis samples showed that CPP was generally the most abundant C18H10 isomer, followed by CPAP and BF. CPAA was detected only in pyrolysis products from pure PAHs. We tested the four C18H10 PAHs for mutagenicity in a forward mutation assay using S. typhimurium. CPP, BF, and CPAA were roughly twice as mutagenic as benzo[a]pyrene (BaP), whereas CPAP was only slightly active. These PAHs were also tested for mutagenic activity in human cells. In this assay, CPP and CPAA were strongly mutagenic but less active than BaP, whereas CPAP and BF were inactive at the dose levels tested. Also, the bacterial and human cell mutagenicity of CPAA and CPAP were compared with the mutagenicity of their monocyclopenta-fused analogs, aceanthrylene and acephenanthyrlene. Although the mutagenicities of CPAP and acephenanthrylene are similar, the mutagenic activity of CPAA is an order of magnitude greater than that of aceanthyrlene. PMID- 8354202 TI - Chemical nature and immunotoxicological properties of arachidonic acid degradation products formed by exposure to ozone. AB - Ozone (O3) exposure in vivo has been reported to degrade arachidonic acid (AA) in the lungs of rodents. The O3-degraded AA products may play a role in the responses to this toxicant. To study the chemical nature and biological activity of O3-exposed AA, we exposed AA in a cell-free, aqueous environment to air, 0.1 ppm O3, or 1.0 ppm O3 for 30-120 min. AA exposed to air was not degraded. All O3 exposures degraded > 98% of the AA to more polar products, which were predominantly aldehydic substances (as determined by reactivity with 2,4 dinitrophenylhydrazine and subsequent separation by HPLC) and hydrogen peroxide. The type and amount of aldehydic substances formed depended on the O3 concentration and exposure duration. A human bronchial epithelial cell line (BEAS 2B, S6 subclone) exposed in vitro to either 0.1 ppm or 1.0 ppm O3 for 1 hr produced AA-derived aldehydic substances, some of which eluted with similar retention times as the aldehydic substances derived from O3 degradation of AA in the cell-free system. In vitro, O3-degraded AA induced an increase in human peripheral blood polymorphonuclear leukocyte (PMN) polarization, decreased human peripheral blood T-lymphocyte proliferation in response to mitogens, and decreased human peripheral blood natural killer cell lysis of K562 target cells. The aldehydic substances, but not hydrogen peroxide, appeared to be the principal active agents responsible for the observed effects. O3-degraded AA may play a role in the PMN influx into lungs and in decreased T-lymphocyte mitogenesis and natural killer cell activity observed in humans and rodents exposed to O3. PMID- 8354203 TI - Lung cancer in the lower lobe is associated with pulmonary asbestos fiber count and fiber size. AB - We studied exposure to asbestos, pulmonary fibrosis, fiber count, and fiber size in relation to the lobar origin of lung cancer in 90 consecutive patients. Among the 32 patients with a history of occupational exposure to asbestos, 22 were construction workers. The proportion of lower-lobe tumors increased with the duration of exposure from 45% in those working less than 15 years to 82% in those working 15 years or more in the construction trade, as compared with 25% in patients who were probably not exposed. The location of the tumor in the lower lobe was explained by the high number of total fibers [odds ratio (OR) = 9.0, CI = 2.3-34.6), of fibers 3 microns and longer (OR = 22.1, CI = 3.9-125), and fibers of anthophyllite (OR = 14.6, CI = 2.4-83.4) and crocidolite (OR = 7.0, CI = 1.2 41.2) when the effect of smoking and fibrosis was adjusted in the logistic regression analysis. The location of the tumor did not correlate with fibrosis, pack-years smoked, or the number of short (< 3 microns) fibers. Our findings suggest that asbestos causes an excess of lower-lobe tumors at a relatively low exposure level, independently of pulmonary fibrosis. PMID- 8354204 TI - Studies with 1,2-dithiole-3-thione as a chemoprotector of hydroquinone-induced toxicity to DBA/2-derived bone marrow stromal cells. AB - Stromal cells from DBA/2 mouse bone marrow have been shown to be susceptible to cytotoxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). Treatment with HQ also alters the composition of stromal cell populations by preferentially killing stromal macrophages compared to stromal fibroblasts. This cytotoxicity can be prevented by 1,2-dithiole-3-thione (DTT) as a result of the induction of quinone reductase (QR), a quinone-processing enzyme, and glutathione. The inductive activities of DTT protected stromal cells against HQ-induced cytotoxicity and against HQ-induced impairment of stromal cell ability to support myelopoiesis. In vivo feeding of DTT to DBA/2 mice increased QR activity within the bone marrow compartment and protected bone marrow stromal cells isolated from the DTT-fed animals from ex vivo HQ challenge. Thus, the inducibility of cellular defense mechanisms and xenobiotic-processing enzymes by chemoprotective agents such as DTT may be a useful strategy for protecting against chemically induced bone marrow toxicities. PMID- 8354205 TI - Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats. AB - The repeated administration of mercury to rats of the Brown Norway (BN) inbred strain results in a self-limiting production of autoantibodies to renal antigens (e.g., laminin) and autoimmune glomerulonephritis. In contrast, rats of the Lewis (LEW) strain do not develop renal autoimmunity after mercury treatment. Suppressor T-cells and/or the idiotype-anti-idiotype network have been implicated in the control of autoimmunity in susceptible (BN) rats as well as the "resistant" state of nonsusceptible (LEW) animals. In our investigations of the immune regulation of mercury-induced autoimmune glomerulonephritis, we have performed a phenotypic analysis of lymphocyte subpopulation in the spleens and lymph nodes of mercury-treated and control LEW, BN, and (BN x LEW) F1 hybrid rats. Of particular interest were RT6+ T-cells, a subpopulation of lymphocytes that may have immunoregulatory properties and show a relative decrease in mercury treated BN rats concomitantly with the development of autoimmune responses to renal autoantigens. LEW rats did not develop renal autoimmunity after mercury treatment and had no significant change in the ratio of RT6+ to RT6- T lymphocytes. Interestingly, the administration of mercury to (BN x LEW) F1 hybrid rats caused effects similar to those observed in the BN strain. Auto-immune responses to antigens of the kidney coincided with a change in the balance within the RT6 cell population, which was altered in favor of T-lymphocytes that do not express the RT6 phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354206 TI - Chronic obstructive pulmonary disease (heaves) as an inflammatory condition. PMID- 8354207 TI - Intra-operative cardiac arrest: routes to recovery. PMID- 8354208 TI - Responses of horses affected with chronic obstructive pulmonary disease to inhalation challenges with mould antigens. AB - Eight control and 8 asymptomatic COPD-affected horses were given, on separate occasions, inhalation challenges with extracts of Micropolyspora faeni, Aspergillus fumigatus and Thermoactinomyces vulgaris. All horses were also given nebulised phosphate-buffered saline (PBS) challenges and 'natural challenges' (NCs), i.e. exposure to hay and straw, as control challenges. Responses were assessed by clinical, pulmonary mechanics, arterial blood gas tensions, arterial blood pH and bronchoalveolar lavage fluid cytological examinations. PBS challenges had no effect on control or COPD-affected horses, while NC induced COPD only in the COPD-affected horses. Pulmonary disease, similar to naturally occurring COPD, was induced, only in the COPD-affected horses, by M. faeni and A. fumigatus challenges, thus implicating these organisms in the aetiology of equine COPD. The role of T. vulgaris in the aetiology of equine COPD could not, however, be determined because the T. vulgaris challenges, in addition to inducing pulmonary disease in 4 COPD-affected horses, induced pulmonary disease in 2 control horses which had been unaffected by NC. The absence of pulmonary disease in control horses after M. faeni, A. fumigatus and NC challenges suggests that equine COPD is a pulmonary hypersensitivity, rather than a non-specific toxic response. PMID- 8354209 TI - Evaluation of local endobronchial antigen challenges in the investigation of equine chronic obstructive pulmonary disease. AB - Local transendoscopic endobronchial antigen challenge, which has proved to be a valuable clinical and research technique in the study of human pulmonary hypersensitivity, was evaluated in control and asymptomatic COPD--affected horses. Transendoscopic endobronchial challenges with phosphate-buffered saline (PBS), Micropolyspora faeni extract at 60 and 600 micrograms/ml and mouldy hay extract elicited neutrophilic airway inflammatory responses in control (N = 5-7) and asymptomatic COPD-affected (N = 5-7) horses, as determined by cytological examinations of bronchoalveolar lavage fluid (BALF) harvested from the challenged lung segments. Endobronchial challenges with 600 micrograms M. faeni extract/ml induced a significant BALF neutrophilia only in horses with asymptomatic COPD, when compared with PBS challenges. However, as the BALF neutrophil ratios of COPD affected horses after this M. faeni challenge did not differ significantly from those of control horses, this finding has little clinical diagnostic value. The BALF neutrophilia induced in control and asymptomatic COPD-affected horses by 60 micrograms M. faeni extract/ml and mouldy hay extract challenges was not significantly different from that induced by PBS challenge. Endoscopically visible bronchial changes were observed in some of the control and COPD-affected horses within 5 mins and at 5 h after PBS, M. faeni and mouldy hay extract challenges. We conclude that this technique is of no value in the investigation of equine COPD. PMID- 8354210 TI - Evaluation of intradermal mould antigen testing in the diagnosis of equine chronic obstructive pulmonary disease. AB - Intradermal end-point titres for commercial aqueous extracts of Micropolyspora faeni, Thermoactinomyces vulgaris and Aspergillus fumigatus were determined in control and chronic obstructive pulmonary disease (COPD) affected horses. The intradermal end-point titres of control and COPD-affected horses were not significantly different and values for individual horses for M. faeni, A. fumigatus and T. vulgaris were not correlated with the pulmonary dysfunction or with the bronchoalveolar lavage fluid neutrophilia which had been induced by previous inhalation challenges with these antigens and by 'natural (hay and straw) challenges'. These findings suggest divergence of the dermal and pulmonary reactivities to M. faeni, A. fumigatus and T. vulgaris in the horse and indicate that intradermal mould antigen testing is of limited value in the investigation of equine COPD. PMID- 8354211 TI - Clinical pharmacokinetics of amikacin in hypoxic premature foals. AB - The pharmacokinetics of amikacin, administered iv at 7 mg/kg, every 8 h, were evaluated over the first 48 h of hospitalisation in 7 critically ill hypoxic premature foals and compared with those in 8 full-term nonhypoxic critically ill neonatal foals. The pharmacokinetic data were used to calculate dosage schedules that would maintain the plasma amikacin concentrations in individual foals within a target range of > or = 15 micrograms/ml but < 30 micrograms/ml for peak values and < or = 3 micrograms/ml for trough values. The results indicated a statistically significant increase in the amikacin serum half-life (5.39 +/- 3.46 h) and smaller elimination rate constant (0.17 +/- 0.09 h-1) in premature foals. The pharmacokinetic derangements required increasing the dose to 8.5-10.5 mg/kg bwt in 6 of 7 premature foals and an increase in the dosage interval to 12-24 h in all 7 foals. Overall, the total dosage of amikacin was decreased in the hypoxic, premature foals so that target peaks and troughs could be maintained. Our findings suggest that prematurity and hypoxia are variables related to a prolonged serum half-life of amikacin in hypoxic, premature foals. Although there was no evidence of amikacin-induced nephrotoxicity in any of these foals, daily monitoring and tailoring of the dose schedule to the individual foal are strongly advised. PMID- 8354212 TI - Cardiovascular effects of thoracic compression in horses subjected to euthanasia. AB - Six horses scheduled for euthanasia were instrumented for the measurement of blood flow by thermodilution, pulmonary arterial, right atrial and arterial blood pressures and collection of arterial blood for pH and blood gas analysis. The horses were anaesthetised with intravenous (iv) thiamylal sodium (10 mg/kg) and placed in right lateral recumbency. After euthanasia with an overdose of pentobarbitone sodium (100 mg/kg, iv) and loss of the electrocardiogram and arterial pulse pressure, thoracic compression at rates of 40, 60 and 80 compressions/min was instituted. Thoracic compression was accomplished by an investigator who delivered a blow to the chest wall with his knee while dropping from a standing or crouching position. Compression rates of 40, 60 and 80/min produced blood flows of 5.65 +/- 0.5, 6.33 +/- 1.11 and 8.28 +/- 2.16 litres/min, respectively. Compression rates of 80/min produced significantly (P < 0.05) greater blood flows and mean arterial blood pressures than did slower rates. The blood flows produced by 80 thoracic compressions/min were approximately 50% of those reported for deeply anaesthetised horses and while not sufficient to sustain life might be used to prolong life in order to facilitate distribution of resuscitative drugs to vital tissues. PMID- 8354213 TI - Characterisation of osseous bodies of the distal phalanx of foals. AB - The distal phalanx and metacarpal physis of both forelimbs of 32 Thoroughbred foals 3-32 weeks of age were radiographed to identify those limbs with osseous bodies at a palmar process (PP) of the distal phalanx. Osseous bodies (ossicles) were identified radiographically in 19% of the foals. Sixteen of the 32 foals were selected for microradiographic and histological evaluation: 6 foals with radiographic evidence of ossicles and 10 foals without. Fourteen ossicles of the PP were observed radiographically. Ossicles were either a triangular bone fragment at the palmar aspect of the distal angle of the PP, or an oblong bone fragment separated from P3 by a radiolucent line extending 1-3 cm from the incisure of the PP to the solar margin. One foal had radiographic evidence of bilateral distal metacarpal physitis. Seventeen of 35 PPs examined microradiographically were considered normal, in that the dorsal and solar cortices were thin with trabecular bone orientated parallel to the cortical surfaces, and there was a depression in the dorsal cortical surface (i.e. parietal sulcus). Abnormal microradiographic findings in the other 18 PPs included a fracture line extending from the dorsal cortical surfaces and trabecular bridging of the fracture gap. The fracture line was often continuous with the parietal sulcus. Microradiographic evidence of a fracture was found in 75% of foals evaluated. Normal histological findings in 16 PPs included thin dorsal and solar cortices with trabeculae orientated parallel to the cortical surfaces, parallel-fibred dense connective tissue attachments of the deep digital flexor tendon to the solar cortical surfaces, and a neurovascular bundle associated with the parietal sulcus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354214 TI - Radiographic and microscopic correlation of diffuse interstitial and bronchointerstitial pulmonary patterns in the caudodorsal lung of adult thoroughbred horses in race training. AB - Complete thoracic radiographic examinations were performed on 7 horses ranging in age from 24 to 60 months, followed by in-situ lung fixation. Radiographs were examined by 3 radiologists for the presence, degree and distribution of generalised pulmonary patterns within a region of interest in the caudodorsal lung. Pulmonary tissue was obtained from 12 sites within a designated volume of interest in the caudodorsal lung, corresponding to the area of interest evaluated radiographically, and examined for the presence, character and severity of microscopic lesions. Radiographic findings within the volume of interest consisted of mild to moderate bronchial, bronchointerstitial, or interstitial pulmonary patterns. Interstitial and bronchointerstitial radiographic findings were related to severity of peribronchiolar mononuclear cell infiltrates, the degree of bronchiolar mucosal plication, and alveolar capillary and peribronchial blood vessel erythrocyte content. The severity of the interstitial radiographic pattern was inversely associated with the perceived diagnostic quality of the radiographic examinations. There was no evidence of spatial variation in the severity of the microscopic changes examined in this limited pulmonary region. Inter-rater reliability between radiologists was good in the assessment of diagnostic quality of the radiographic examinations but poor in assessing severity of the primary generalised pulmonary patterns within the radiographic region of interest. PMID- 8354215 TI - The airway response of horses with recurrent airway obstruction (heaves) to aerosol administration of ipratropium bromide. AB - The airway response to aerosol administration of the anticholinergic agent ipratropium bromide was determined in 8 horses with recurrent airway obstruction (heaves). The reversibility of airway obstruction was confirmed by measuring lung function before and during stabling; and by determining the response to atropine administration (0.02 mg/kg bwt intravenously). The dose-response to ipratropium bromide was determined using a Williams square design experiment in which 25, 50 or 75 micrograms ipratropium bromide/ml (4 ml/100 kg bwt) or the same volume of vehicle was administered to each horse by nebulisation. Lung function was measured before and 1 and 4 h after nebulisation. Vehicle had no effect on lung function. Ipratropium decreased the maximal change in pleural pressure during tidal breathing (delta Pplmax) and pulmonary resistance (RL) and increased dynamic compliance (Cdyn). At the 1 h measurement period, the effect on RL and Cdyn was dose-dependent. A separate experiment demonstrated that the duration of action of ipratropium was between 4 and 6 h. PMID- 8354216 TI - Paravertebral thoracolumbar anaesthesia in 10 horses. AB - The caudal border of the last rib was used as a reliable point of orientation while performing paravertebral thoracolumbar anaesthesia (PTLA) on 10 horses undergoing standing flank laparotomy. The local anaesthetic in all horses was 2% lidocaine. The PTLA procedure was completed in 9.8 +/- 1.8 mins (mean +/- sd). Sedation was provided by a combination of intravenous morphine with xylazine or detomidine. Overall analgesia, provided by the combination of PTLA and sedation, was rated as excellent in 2 horses and good in 6 horses. In the remaining 2 horses, overall analgesia was rated as fair because of incomplete analgesia at the ventral portion of the incision. Total time, from start of PTLA to end of surgery was 143.5 +/- 24.2 mins. Five horses responded mildly to suturing of the ventral portion of the incision. Apart from 1 horse which developed transient, unilateral hindlimb weakness intraoperatively, no other complications were noticed. We conclude that PTLA can easily be performed in the horse and, combined with systemic sedation, is an effective and safe method of providing analgesia for standing flank laparotomy. PMID- 8354217 TI - In-vitro susceptibility to antimicrobial drugs of bacterial isolates from horses in The Netherlands. AB - Minimum inhibitory concentrations (MICs) of 30 antimicrobial agents (including the hitherto unreported antimicrobial agents doxycycline, minocycline, vanomycin, 3 quinolones and 3 combinations of antimicrobial agents) for isolates of Salmonella spp. (20), Escherichia coli (17), Klebsiella spp. (8), Proteus spp. (7), Pseudomonas aeruginosa (7), Actinobacillus equuli (5), Rhodococcus equi (4), Streptococcus zooepidemicus (23), Streptococcus equisimilis (6), Streptococcus equi (4), coagulase-positive Staphylococcus spp. (20) and Taylorella equigenitalis (19) were determined using the agar dilution method. All isolates were of equine origin. MICs were compared with recommended MIC breakpoints. The results indicate that, for some of the pathogenic bacteria evaluated, susceptibility testing of isolates from the individual patient is essential to determine an appropriate antimicrobial treatment. PMID- 8354218 TI - Streptococci and Pasteurella spp. associated with disease of the equine lower respiratory tract. AB - The likelihood of finding evidence of inflammation in 551 tracheal washes collected endoscopically from 278 Thoroughbred racehorses increased with the number of bacterial colony forming units (cfu) per ml of wash (P < 0.001). The aerobic bacteria Streptococcus zooepidemicus, Pasteurella/Actinobacillus-like species and Streptococcus pneumoniae were significantly associated with lower airway inflammation whereas coagulase-negative Staphylococcus spp., alpha haemolytic Streptococcus spp., Acinetobacter spp., Bacillus spp., Escherichia coli, Pseudomonas aeruginosa, non-haemolytic Streptococcus spp. and Enterobacteriaceae were not; Bordetella bronchiseptica was not isolated. Lower airway inflammation was particularly associated with bacteria in horses < or = 3 years of age. S. zooepidemicus, S. pneumoniae and Pasteurella/Actinobacillus-like species were isolated from 167 of 551 washes, either alone or in combination. PMID- 8354220 TI - More theories than facts: equine rhabdomyolysis. PMID- 8354219 TI - Predictable ovulation in mares treated with an implant of the GnRH analogue deslorelin. PMID- 8354221 TI - Dorsal displacement of the soft palate in neonatal foals. PMID- 8354222 TI - Clinical, cytogenetic and endocrine evaluation of a horse with a 65,XXY karyotype. PMID- 8354223 TI - Partial re-establishment of villous placentation after reduction of an equine co twin by foetal cardiac puncture. PMID- 8354224 TI - High-performance capillary electrophoresis of glycoconjugates. AB - Capillary electrophoresis (CE) has recently emerged as a highly promising technique for the analysis and structural study of glycoconjugates. This article reviews the current status of CE and its potential in glycobiology. The separation media suitable for the analysis of monosaccharides, oligosaccharides and very large carbohydrate-based biomolecules are discussed. The detection aspects emphasize chemical derivatization approaches to tagging the glycoconjugates of interest for enhanced response in absorption and fluorescence spectroscopy. PMID- 8354225 TI - Studies in capillary zone electrophoresis with a post-column multiple capillary device for fraction collection and stepwise increase in electroosmotic flow during analysis. AB - A new approach involving the stepwise increase in electroosmotic flow during analysis in capillary zone electrophoresis is introduced and evaluated in the rapid separations of proteins and peptides. The stepwise increase in electroosmotic flow is based on the principle of coupled capillaries in series having different flow characteristics, a concept that was introduced recently by our laboratory. To produce stepwise changes in electroosmotic flow during analysis, a post-column multiple capillary device, which allowed the switching between several coupled capillary systems, was designed and constructed in-house. The utility of the multiple capillary device was also demonstrated and extended to fraction collection of separated analytes in short capillary segments. The fraction collection in capillaries facilitated the quantitative transfer of the collected fractions to high performance liquid chromatography (HPLC) for further analysis or to mass spectrometry (MS) for structural determination. The off-line combination of capillary zone electrophoresis with HPLC or MS utilized commercial instruments without the need of expensive interfacing designs. PMID- 8354226 TI - Screening and characterization of biopharmaceuticals by high-performance capillary electrophoresis with laser-induced native fluorescence detection. AB - High-performance capillary electrophoresis (HPCE) with laser-induced native fluorescence (LIF) detection is used to address significant problems in the quality control of biopharmaceuticals. All of the biopharmaceuticals studied can be detected at subnanomolar levels with linear dynamic ranges of at least 3 orders of magnitude. HPCE/LIF can determine impurities in "purified" biopharmaceuticals present in amounts less than 0.01% (i.e., at 4 x 10(-11) M) that of the major component. With HPCE/LIF, detection sensitivity is thus no longer a concern in the assaying of active ingredients in biopharmaceutical dosage formulations. The peptide mapping of biopharmaceuticals present at 1 x 10( 7) M (or an injected limit of detection of 60 amol) is presented. Also, kinetic information on the reaction of a recombinant enzyme-drug with its substrate present at the micromolar level has been extracted from electropherograms acquired in real-time. PMID- 8354227 TI - Two-dimensional separations of peptides and proteins by comprehensive liquid chromatography-capillary electrophoresis. AB - Analysis of biological samples is problematic because of their complex composition. Reversed phase liquid chromatography (RPLC), size exclusion chromatography (SEC), and, more recently, capillary zone electrophoresis (CZE) are routinely used for the analysis of these samples, but are eventually limited because they are one-dimensional (1-D) methods. As sample complexity increases, the separation efficiency necessary to resolve a large number of sample components in one dimension becomes prohibitively high. A solution to this problem has been to use a two-dimensional (2-D) approach. Each dimension in a 2-D separation relies on a different separating mechanism. By expanding the separation into two dimensions, sample components unresolved in the first dimension can often be separated in the second. This circumvents the requirement for extremely high efficiencies in either dimension. Two-dimensional slab gel electrophoresis has been used successfully in this area, but a more instrumental approach is desired. In this paper we describe three coupled-column approaches to 2-D separations. First, microcolumn SEC-CZE is explored as a means of 2-D protein analysis. Next, RPLC-CZE is investigated for analysis of peptides in tryptic maps. Finally, RPLC is coupled with fast CZE (FCZE), a unique form of CZE analysis, for fast 2-D analysis of peptides. Details of the instrumentation used in these 2-D systems will be presented along with the results of some typical 2-D analyses. PMID- 8354228 TI - Use of small-diameter capillaries for increasing peptide and protein detection sensitivity in capillary electrophoresis-mass spectrometry. AB - The use of small ID capillaries is shown to provide a substantial increase in sensitivity for capillary electrophoresis-electrospray ionization/mass spectrometry (CE-ESI/MS). In a comparison using capillaries ranging from either 100 to 10 microns or 50 to 5 microns ID and chemically modified with aminopropylsilane, a 25- to 50-fold increase in sensitivity was observed for both peptide and protein mixtures. This enhanced solute sensitivity allowed the detection of approximately 150 attomoles of melittin (2845 Da) with selected ion monitoring and 600 attomoles of carbonic anhydrase (29,157 Da) while scanning for CE-MS with a quadrupole mass spectrometer. For the protein mixture, mass spectra of sufficient quality for precise molecular weight determination (< or = 0.05%) were obtained for 600 attomole injections using a 5 microns ID capillary. The increase in sensitivity with small capillary diameters can be primarily attributed to a reduced mass flow rate of buffer and other background constituents into the electrospray source, which allows for greater sample ionization efficiency. A model that qualitatively accounts for the results is presented, but quantitative agreement is precluded due to difficulties in accounting for contributions due to a liquid sheath flow used with the electrospray source. The model accounts for the observation that the ESI/MS appears to function as a concentration-sensitive detector under many conditions using large-diameter capillaries. A transition occurs, however, to a regime where the ESI/MS functions as a mass flow-sensitive detector for small-diameter capillaries, where the ESI current is limited by the rate of delivery to the ESI source of charge carrying species in solution. These results suggest peptide and protein analysis at low attomole and subattomole levels should be obtainable with alternative types of mass spectrometers. PMID- 8354229 TI - The characterization of snake venoms using capillary electrophoresis in conjunction with electrospray mass spectrometry: Black Mambas. AB - Capillary electrophoresis has been used in conjunction with electrospray mass spectrometry using both full-scan and selected ion monitoring modes to supply as much information as possible about the venom of Dendroaspis polylepis polylepis (Black Mamba). As an example of the application of capillary electrophoresis/electrospray mass spectrometry (CE/ESI/MS) to the analysis of a complex mixture of small proteins, we have analyzed the venom of Dendroaspis polylepis polylepis using the combined techniques. Both full-scan and selected ion monitoring modes were employed. CE/ESI/MS provides a rapid and extremely sensitive method for molecular weight determination, particularly when selected ion monitoring is employed. It has been utilized to provide sequence confirmation for those toxins which have already been described in the literature. Our methodology indicates the presence of at least 70 peptides in the molecular weight range 6000-9000. PMID- 8354230 TI - Fast analysis of proteins by isoelectric focusing performed in capillary array detected with concentration gradient imaging system. AB - Isoelectric focusing of several protein samples is performed simultaneously in an array of 2-4 short capillaries (4-10 cm long). The separated proteins are detected by either an on-line concentration gradient imaging detection system, or a single point concentration gradient detector which requires a mobilization step following the focusing process. The application of the capillary array increases the throughput of the capillary isoelectric focusing (CIEF) technique, and makes the technique comparable in sample throughput to the gel slab isoelectric focusing technique, but with much faster speed of separation and quantitation. The analysis is completed in 2-3 min with the imaging detection system, which is about 100 times faster than the conventional gel slab isoelectric focusing and 10 times faster compared to conventional CIEF. The resolution of the separation is 0.02 pH units or better. All separated proteins in the capillary array are detected by the universal concentration gradient detector, which eliminates the need for sample derivatization. The concentration limit of detection for the inexpensive instrument described in this work is about 30 micrograms/mL and can be reduced by using higher quality components in the system, such as a more stable laser, higher optical quality capillaries and a faster computer A/D board. The sample consumption is 400 nL for the 4 cm long, 100 microns ID square capillary. The isoelectric point (pI) values of the samples can be directly determined without internal pI markers from their positions inside the capillary after focusing when the imaging detection system is used. PMID- 8354231 TI - Determination of the isoelectric points of low and high molecular mass ampholytes by capillary electrophoresis. AB - A methodology for a reliable and absolute determination of isoelectric points of amphoteric species by capillary zone electrophoresis is proposed. The principle of this absolute method consists in the application of an additional electroosmotic and/or hydrodynamic flow of a background electrolyte. This allows the measurement of electrophoretic mobilities of substances close to their isoelectric points where the net electric charge is very low and electrophoretic mobility tends to zero. The mobilities are measured at various pH values of the electrolyte so as to find the pH at which the substance moves through the separation column at zero mobility under the action of the additional flow only. The number of required measurements is lowered to the minimum with the help of the iterative procedure based on the Regula Falsi algorithm. The precision of the proposed method is predicted theoretically. The feasibility is demonstrated on real samples. The isoelectric points of histidine, myoglobine and ribonuclease are found from their titration curves. PMID- 8354232 TI - Application of high-performance capillary electrophoresis to the analysis of H1 histones. AB - High-performance capillary electrophoresis for the separation of rat testis H1 histone variants and their phosphorylated modifications is described. The influence of buffer pH, hydroxypropylmethyl cellulose, and buffer concentration has been investigated. Under optimized conditions (500 mM phosphate buffer, pH 2, 0.03% hydroxypropylmethyl cellulose) using an uncoated capillary, eight H1 histone subfractions, including two H1(0) histones and H1t and their phosphorylated modifications, are resolved. Application of capillary electrophoresis to the separation of H1 histones provides an important new alternative to high-performance liquid chromatography (HPLC) and traditional gel electrophoresis. PMID- 8354233 TI - Using capillary electrophoresis in the optimization of a carboxypeptidase Y catalyzed transpeptidation reaction. AB - A peptide amide, R-Arg-NH2, was produced by carboxypeptidase Y (CPDY)-catalyzed transpeptidation of a peptide, R-Ala-OH in presence of a large excess of Arg-NH2. Baseline separation of R-Ala-OH and R-Arg-NH2 was achieved by free solution capillary electrophoresis (CE) analysis. With CE the reactions could be closely followed with an analysis frequency of 3-6 h-1. Due to a low consumption of sample per CE analysis (1-5 nL introduced, 5-6 microL in the sample vial), the reactions were performed in 100 and 250 microL volumes. Consequently, the optimization experiments consumed limited amounts of enzyme and substrate only. At optimized experimental conditions approximately 90% conversion of the starting peptide, R-Ala-OH, to R-Arg-NH2 was achieved. PMID- 8354234 TI - A model for the mobility of single-stranded DNA in capillary gel electrophoresis. AB - The electrophoretic mobility of single-stranded DNA in denaturing polyacrylamide gel-filled capillaries is analyzed as a function of the applied electric field. The resultant mobility plots are complex functions of the fragment size and electric field. Traditionally, these plots are separated into three mobility regimens corresponding to Ogston sieving, reptation without stretching and reptation with stretching theories. However, none of these theories accurately models the variations in mobility that we observe with electric field strength. As a result, we propose a modification of the Ogston sieving theory which accounts for the stretching of migrating DNA molecules in the direction of the electric field. This theory assumes that the applied electric field in conjunction with the gel matrix distorts the DNA, altering the effective size of the migrating molecule. The stretched DNA offers a smaller cross-section to the gel pore and thus sieves as though it were a smaller molecule. In this modified Ogston theory, the electrophoretic mobility depends only on the applied electric field, the size of the fragment, and constants which are independent of size and field strength. The modified Ogston equation accurately predicts the mobilities of DNA fragments in all three mobility regimes, providing a single, simple model to account for all of the observed behavior. PMID- 8354235 TI - Contribution of secondary structure to DNA mobility in capillary gels. AB - Intramolecular base pairing at the 3' end of single-stranded DNA molecules can cause increased electrophoretic mobility. In DNA sequencing separations this can result in compressions, where multiple oligomers differing in length by one base comigrate, which complicate sequence analysis. Using a novel approach to the application of capillary electrophoresis to DNA sequencing, incorporation of formamide into capillary gels, different separation field strengths, and external heating of the capillary are examined for their ability to resolve compressions. The identity of the 3' terminal nucleotide has also been observed to influence oligomer mobility in cross-linked acrylamide slab gels. We utilize automated data collection from DNA sequencing separations to show that a similar effect is also present in linear acrylamide capillary gels run at high field strengths. We also demonstrate the ability of capillary electrophoresis to separate synthetic oligos of the same length but differing in composition by one base, or of the same base composition but different sequence. PMID- 8354236 TI - Ultrasensitive plasmid mapping by high performance capillary electrophoresis. AB - This paper compares high performance capillary electrophoresis (HPCE) and conventional slab electrophoresis in mapping of four closely related plasmids with three different restriction enzymes. The plasmids express full length and truncated forms of a growth factor receptor oncogene product and were digested with HpaII, HaeIII and RsaI. The resulting oligonucleotide fragments were under 2000 base pairs in length, a size well suited to separation by HPCE with linear polyacrylamide as a sieving matrix. Plasmid mapping is an essential tool in biotechnology both for the design of an expression system and for monitoring the stability of the expression system during fermentation. HPCE can yield much higher resolution of oligonucleotides than attainable in conventional agarose gel electrophoretic procedures for plasmid mapping. In the examples described here, the HpaII digests provided the surest identification of individual plasmids in the HPCE analysis and could discriminate among all four plasmids. In conventional slab electrophoresis, however, the RsaI digests provided the best discrimination, although two of the plasmids in this system yielded essentially identical electrophoretic patterns. Hence the optimal restriction enzyme for plasmid mapping applications with HPCE may differ from that selected on the basis of conventional slab gel analysis, and the former technique can provide higher discrimination among related plasmids. The advantages of the HPCE format with respect to speed, low sample consumption and resolution are described. PMID- 8354237 TI - Capillary electrophoresis of DNA restriction fragments with solutions of entangled polymers. AB - Separation of DNA restriction fragments in dilute buffer solutions of network forming polymers such as linear polyacrylamide (PAA), hydroxyethyl cellulose (HEC) and polyvinylalcohol (PVA) in phosphate buffer were investigated. PVA in buffers already became inhomogeneous after a few separations with resultant deterioration of resolution. Hydroxylic polymers, capable of forming suitable networks in buffers, are strongly adsorbed to fused silica surfaces suppressing the electroosmotic flow. These polymers could be applied as surface modifiers in capillaries, filled with buffer media containing other polymers such as PAA. Suppression of the electroosmotic flow by adsorbed HEC at pH 7 was slightly more effective than with PVA but the former coating was less stable due to weaker binding to the fused silica surface. Good separations of restriction fragments could be achieved with solutions of PAA or HEC as separation media after surface pretreatment of fused silica capillaries by either PVA rinsing or coating according to Hjerten. PMID- 8354238 TI - Capillary zone electrophoresis of large DNA. AB - Capillary zone electrophoresis (CZE) of DNA 23.1 to 48.5 kb in length in polyacrylamide solutions of several concentrations provides evidence for polymer concentration and DNA length-dependent stretching and orientation of these species and suggests an effective separation at a polymer concentration of about 0.6%. Applying a 0.1% polyacrylamide concentration to the lambda-phage DNA ladder, at least 5 components are separated; separation improves with lowering of the field strength to 2 V/cm and, correspondingly, extended duration of CZE. Saccharomyces pombe chromosomal DNA separates into 3 major components on CZE at high field strength (270 V/cm) in 0.9% polyacrylamide solution, confirming a previous finding made on electrophoresis in a 1.1 mm ID tube at low field strength. However, the finding is limited to one source of the DNA plug, and the chromosomal identity of the components remains unknown. Methodological problems in the CZE of large DNA relate to the need for extended duration of pressure injection if absorbance detection is applied, the need to define the starting zone after extended pressure injection, the need to melt and digest agarose plugs prior to loading, and related needs for thermostating of the sample chamber and for software compatible with low voltage operation. PMID- 8354239 TI - Capillary electrophoresis/mass spectrometry determination of inorganic ions using an ion spray-sheath flow interface. AB - The determination of inorganic cations and anions by capillary electrophoresis/mass spectrometry (CE/MS) is reported using an ion spray-sheath flow interface coupling. A twelve-component synthetic mixture of cations which included the positive ions of K, Ba, Ca, Mn, Cd, Co, Pb, Cr, Ni, Zn, Ag, and Cu was loaded into the capillary column at levels ranging from 30 to 300 pg, separated by CE, and detected by indirect UV and in the full-scan (m/z 35-450) positive ion CE/MS mode using an aqueous buffer containing 30 mM creatinine and 8 mM alpha-hydroxyisobutyric acid, pH 4.8. Creatinine forms adducts with the cations which are observed in the gas phase and requires rather high (120 electron volts) declustering energy to dissociate. This produces a reduction in charge state to form the free, singly charged, inorganic cations which are observed in the mass spectra. CE/MS analysis of an aqueous acidic extract of used aircraft engine oil revealed high levels of lead as well as lower levels of chromium and nickel. CE-indirect UV analysis of a synthetic mixture containing 300 pg each of 11 inorganic ions, which included the anions of Br, Cl, NO2, NO3, S2O3, N3, SCN, SO4, SeO4, oxalate, and MoO4, is shown. The running buffer which affected this separation contained 5 mM ammonium dichromate, 10 mM ammonium acetate, and 20 mM diethylenetriamine at pH 9.3. Although indirect UV detection revealed good separation of these anions, CE/MS analysis of this mixture was complicated by interfering ion current signals from the cluster ions formed by the interaction between the additives and the analytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354240 TI - Application of a diode-array detector in capillary electrophoresis. AB - In the last decade diode-array detection has proved to be extremely useful in high performance liquid chromatography in recording UV-visible spectra directly and on-line in the column effluent. In capillary electrophoresis (CE) only fast scanning detectors with long scan times (up to 2 s) are commercially available. A home-made CE instrument with a diode-array detector (DAD) was built and compared with a commercial fast-scanning detector. It is shown that the fast-scanning detector is advantageous when less than eight wavelengths are monitored. Due to the high data collection rate the DAD is superior if high resolution UV-visible spectra are acquired or if several spectra of a narrow peak (usual peak width in CE below 5 s) are needed for peak purity control. It is shown that DAD detection can help to develop separation methods, to identify peaks according to their UV visible spectra, and to check peak purity. PMID- 8354241 TI - Acetylator phenotyping via analysis of four caffeine metabolites in human urine by micellar electrokinetic capillary chromatography with multiwavelength detection. AB - The simultaneous analysis of 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 5 acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1X) and 1-methyluric acid (1U), the four urinary metabolites of caffeine employed for acetylator phenotyping in man, by micellar electrokinetic capillary chromatography (MECC) is reported. Using on-column fast scanning multiwavelength detection is shown to permit unambiguous identification of AAMU, AFMU, 1X and 1U in the three dimensional electropherograms obtained with both direct urine injection or application of extracted urine. The phenotype status of a number of healthy volunteers, some with known acetylator status, were determined using peak height ratios of AFMU/1X, (AFMU + AAMU)/1X and compared to those obtained by high performance liquid chromatography (HPLC) employing the AFMU/1X peak height ratio. Another set of MECC data was obtained after deliberate conversion of AFMU to AAMU, the results being expressed by AAMU/1X,AAMU/(1U + 1X) or AAMU/(AAMU + 1U + 1X) ratios. The data suggest that most reliable data are obtained when phenotyping is conducted under conditions of complete conversion of AFMU to AAMU. Phenotyping employing caffeine and analysis of its urinary metabolites by MECC is shown to be simple and, with automated instruments, potentially suitable for routine use and large-scale population analysis. The agreement of MECC data obtained from three different instruments demonstrates the high level of maturity of this emerging technology. PMID- 8354242 TI - On the pH dependence of polymerization efficiency, as investigated by capillary zone electrophoresis. AB - The conversion efficiency of 5 different catalyst systems for polyacrylamide gel polymerization has been assessed as a function of pH of the gelling solution, in the pH 4.0-10.0 range. The system of persulfate-N,N,N',N'-tetramethylethylene diamine (TEMED) gives optimal incorporation of monomers only in the pH 7.0-10.0 range; at progressively acidic pH values, the conversion drops markedly until, at pH 4.0, no gelation occurs. In the system of riboflavin-TEMED, the opposite behavior is observed: good conversions in the pH 4.0-7.0 interval (with a peak at pH 6.2), followed by progressive worsening at alkaline pH values until, at pH 10.0, no gelation occurs. An excellent catalyst system appears to be the complex comprising methylene blue, toluene-4-sulfinic acid and diphenyliodonium chloride, which is able to guarantee > 95% conversion in the pH 4.0-8.0 range. Lower efficiencies are obtained at pH 9.0 and 10.0 (down to 81% conversion) but gelation still occurs in the entire pH range. Two other systems (ascorbic acid, ferrous sulfate and hydrogen peroxide in one case, and persulfate, TEMED and hydrosulfite, in another case) have been investigated. The former has some efficiency only at pH 4 (81% conversion), with a rapid drop as pH increases (only 48% incorporation at pH 6). The latter exhibits the opposite behavior: 70% efficiency at pH 4.0, increasing to 92% conversion at pH 6.0. PMID- 8354243 TI - Acetylsalicylic acid has no effects on various isolated immune cells in vitro. AB - In addition to the well known biological effects of acetylsalicylic acid (ASA), its stimulating effect on the immune system has recently been described. In the present study, therefore, the influence of ASA on isolated leucocytes was investigated in vitro. Various concentrations of ASA, representing therapeutic concentrations, had neither an inhibitory nor a stimulating influence on the cytotoxicity of CD16-positive cells. The phytohaemagglutinin-induced proliferation of lymphocytes and the phagocytosis activity of monocytes and neutrophilic granulocytes was similarly unaffected. These results would indicate that the immunostimulating effects already described for ASA cannot be examined in isolated leucocytes in vitro and should be attributed to an interaction of various effector cells in vivo. PMID- 8354244 TI - Continuous percutaneous measurement by laser-Doppler flowmetry of skeletal muscle microcirculation at varying levels of contraction force determined electromyographically. AB - Laser-Doppler flowmetry (LDF) and electromyography (EMG) were used simultaneously for measuring skeletal muscle blood perfusion in relation to static load and fatigue. Percutaneous single-fibre LDF and bipolar surface EMG of the trapezius muscle were performed continuously during a 10-min series of alternating periods of static contractions and rest, each of 1-min duration. The muscle was exposed to static load expressed as shoulder torque, by keeping the arms straight and elevated at 30, 60, 90 and 135 degrees. On-line computer processing of the LDF and EMG signals made possible the interpretation of the relationship between the perfusion and the activity of the muscle. The LDF and root mean square (rms)-EMG were normalized by using the average value of the serial examinations of each individual as a reference value. Spectrum analyses of EMG showed the lowest variability for median frequency (MDF) in the frequency range 10-1000 Hz and mean power frequency (MPF) at 2-1000 Hz. The LDF power spectrum density during low (muscle rest) and high (high-force muscle contraction) perfusion indicated that disturbances were small when measurements were performed during sustained static contraction with as little movement as possible. Vasomotion, i.e. rhythmic variations in the blood flow, were present and showed a frequency of 5-6 cycles.min-1. Application of a tourniquet to the upper arm caused an arrest of the microcirculation in the distally situated brachioradial muscle which was followed by a postischaemic hyperaemia upon removal of the torniquet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354245 TI - Microcirculation in the upper trapezius muscle during varying levels of static contraction, fatigue and recovery in healthy women--a study using percutaneous laser-Doppler flowmetry and surface electromyography. AB - Microcirculation in the upper portion of the trapezius muscle was measured percutaneously by continuous laser-Doppler flowmetry (LDF) during two 10-min series of alternating 1-min periods of static contraction and rest determined electromyographically (EMG). Stepwise increased contraction was induced by keeping the arms straight and elevated at 30, 60, 90 and 135 degrees, which was repeated with a 1-kg load carried in each hand. Thereafter, fatigue and recovery were recorded while the subject kept her arms straight and elevated at 45 degrees carrying the 1-kg hand load as long as possible, followed by rest with arms hanging and no load. A group of 16 healthy women of different ages was studied. Signal processing was done on line using a 386 SX computer. The LDF- and root mean-square (rms) EMG signals were normalized. Spectrum analyses of EMG mean power frequency (MPF) and median spectrum frequency were performed. The rms-EMG increased significantly with an increase in the calculated shoulder torque (r = 0.75). Accumulated local fatigue was indicated by a decrease in MPF with increased shoulder angle and added load (r = -0.54). Blood flow increased with increased shoulder angle (r = 0.82, with hand load r = 0.62) and with increased shoulder torque (r = 0.72), and also showed a significant increase with increased EMG activity (r = 0.74). The LDF showed a negative correlation to MPF (r = 0.67), with increased values when MPF was lowered. During the endurance test, a moderate increase of LDF occurred which reached its maximum during the 1st min of recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354246 TI - Effect of hand paddle aids on oxygen uptake during arm-stroke-only swimming. AB - Cardiorespiratory responses during arm-stroke-only swimming with and without the aid of paddle were compared in seven trained swimmers. Water flow rate was started at 0.80 m.s-1 and was increased by 0.05 m.s-1 every 2 min up. to 1.00 m.s 1. Subsequently, the flow rate was increased by 0.05 m.s-1 every minute until exhaustion. At given submaximal water flow rates, oxygen uptake, heart rate (fc), pulmonary ventilation (VE) and respiratory frequency (fR) during swimming using hands alone (H) were significantly higher than when aided by paddles (P). There were no significant differences in tidal volume (VT) between H and P. The subjects were able to swim significantly faster using paddles (P < 0.05); however, no significant differences between H and P were found in peak oxygen uptake (VO2peak, Fc, VE, FR, VT and the blood lactate concentration at which VO2peak was obtained (P > 0.05). These results would suggest that the ability to swim faster with paddles does not depend on higher energy production but may be attributed to higher propelling efficiency. PMID- 8354247 TI - 31P-nuclear magnetic resonance spectroscopy study of the time course of energy metabolism during exercise and recovery. AB - This study evaluated the time courses of intracellular pH and the metabolism of phosphocreatine (PCr) and inorganic phosphate (Pi) at the onset of four exercise intensities and recoveries. Non-invasive evaluation of continuous changes in phosphorus metabolites has become possible using 31P-nuclear magnetic resonance spectroscopy (31P-MRS). After measurements at rest, six healthy male subjects performed 4 min of femoral flexion exercise at intensities of 0 ("loadless"), 10, 20 and 30 kg.m.min-1 in a 2.1 T superconducting magnet with a 67-cm bore. Measurements were continuously made during 5 min of recovery. During a series of rest-exercise-recovery procedures, 31P-MRS were accumulated using 32 scans spectrum-1 requiring 12.8 s each. At the onset of exercise, PCr decreased exponentially with a time constant of 27-32 s regardless of the exercise intensity. The time constant PCr resynthesis during recovery was about 27-40 s. The PCr kinetics were independent of exercise intensity. There were similar Pi kinetics at the onset of all types of exercise, while those of Pi recovery became significantly longer at the higher exercise intensities (P < 0.05). Furthermore, the intracellular pH indicated temporary alkalosis just at the onset of exercise, probably due to absorption of hydrogen ions by PCr hydrolysis, and then decrease at a point about 40%-50% of the pre-exercise PCr. The pH recovery time was longer than that for the Pi or PCr kinetics. By using a more efficient resolution system it was possible to obtain the phosphorus kinetics during exercise and to follow PCr resynthesis within the first few minutes of recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354248 TI - Kinetics of heart rate and catecholamines during exercise in humans. The effect of heart denervation. AB - To elucidate the role of factors other than the nervous system in heart rate (fc) control during exercise, the kinetics of fc and plasma catecholamine concentrations were studied in ten heart transplant recipients during and after 10-min cycle ergometer exercise at 50 W. The fc did not increase at the beginning of the exercise for about 60 s. Then in the eight subjects who completed the exercise it increased following an exponential kinetic with a mean time constant of 210 (SEM 22) s. The two other subjects were exhausted after 5 and 8 min of exercise during which fc increased linearly. At the cessation of the exercise, fc remained unchanged for about 50 s and then decreased exponentially with a time constant which was unchanged from that at the beginning of exercise. In the group of eight subjects plasma noradrenaline concentration ([NA]) increased after 30 s to a mean value above resting of 547 (SEM 124) pg.ml-1, showing a tendency to a plateau, while adrenaline concentration ([A]) did not increase significantly. In the two subjects who became exhausted an almost linear increase in [NA] occurred up to about 1,300 pg.ml-1 coupled with a significant increase in [A]. During recovery an immediate decrease in [NA] was observed towards resting values. The values of the fc increase above resting levels determined at the time of blood collection were linearly related with [NA] increments both at the beginning and end of exercise with a similar slope, i.e. about 2.5 beats.min-1 per 100 pg.ml-1 of [NA] change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354249 TI - Cardiorespiratory response at the onset of passive leg movements during sleep in humans. AB - To examine the ventilatory response at the onset of passive leg movements during sleep in man and the concomitant changes in cardiac output (Qc), five healthy male subjects had their knee joints extended and flexed alternately at a frequency of about 60.min-1 for about 8 s. Minute ventilation (VI), respiratory frequency, tidal volume, end-tidal partial pressure of carbon dioxide and of oxygen, stroke volume (SV), heart rate (fc) and Qc were measured before, during and after passive leg movement during sleep stage III or IV (SLEEP). These values were compared with those of the awake condition (AWAKE). The VI increased significantly (P < 0.05) compared with the mean of five breaths preceding the movement (pre-movement) within one or two breaths at the onset of passive leg movements in both conditions. The difference between the mean of the first and second breaths after the onset of leg movement and pre-movement was 5.2 (SEM 1.9) l.min-1 for SLEEP and 2.7 (SEM 1.1) l.min-1 for AWAKE, respectively. Four of the five subjects showed a larger increase in ventilation during SLEEP compared with AWAKE. The fc increased significantly (P < 0.05) at the beginning of the passive movement in all cases, while SV showed an increase or decrease so that Qc showed no significant change in either condition. These results would suggest that afferent drive from moving limbs could produce an increase in ventilation without any change in Qc. PMID- 8354250 TI - Muscle strength and history of heavy manual work among elderly trained women and randomly chosen sample population. AB - The association between a history of heavy work and muscle strength was studied among 51 physically active women aged 66-85 years trained in sports and 41 women aged 70-81 years selected randomly from the population register. Maximal isometric muscle strength of hand grip, arm flexion, leg extension and trunk flexion and extension were measured using specially constructed dynamometers. The capacity of the abdominal muscles was evaluated by means of a sit-up test. The study included an interview dealing with the subjects' histories of heavy manual employment. The mean histories of heavy work for the trained and untrained women were 24 and 36 years, respectively. The trained women showed significantly greater maximal isometric muscle strength and abdominal muscle capacity than the untrained women. Among the trained women there was no correlation between the amount of heavy work and muscle performance. Among the untrained women the amount of heavy work correlated positively with maximal isometric trunk extension strength. The results would suggest that among elderly women, whether physically active or not, a history of heavy work has no systematic association with muscle strength. PMID- 8354251 TI - The temperature within the circle of Willis versus tympanic temperature in resting normothermic humans. AB - We measured the temperature of arterial blood within the circle of Willis (T(Willis)) in seven normothermic patients undergoing carotid arteriography. We found this temperature to be lower by 0.13 to 0.30 degrees C than tympanic temperature and by 0.30 to 0.55 degrees C lower than rectal temperature. By imposing this data on calculated cerebral heat balance it can be suggested that the average cerebral temperature of a resting subject is somewhat higher than tympanic temperature. These findings would also support indirectly the thesis that temperature gradients may exist within the brain. PMID- 8354252 TI - Acute and delayed effects of prolonged exercise on serum lipoproteins. I. Composition and distribution of high density lipoprotein subfractions. AB - To investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, the serum of 13 healthy, endurance trained men was examined before and after (1 h, 20 h) a field test [running time, 130 (SD 7.4) min]. We found changes in composition of all of the lipoprotein fractions isolated. In detail, all very low density lipoprotein particle components were reduced after exercise; the most pronounced changes found were in the concentrations of phospholipids (PL) and triglycerides (TG) (PL, before vs 20 h after, P < 0.01; TG, before vs 20 h after, P < 0.01). The serum high density lipoprotein (HDL)-cholesterol mass was unchanged after exercise, but both HDL subfractions showed changes in composition. In HDL3 the relative amounts of cholesterol increased (unesterified free cholesterol; FC) before vs 20 h after, P < 0.05; cholesterylester (CE), before vs 20 h after, P < 0.01) and TG and PL decreased (TG and PL, before vs 20 h after, P < 0.05). The HDL2 particles became enriched in the relative amount of CE (before vs 20 h after, P < 0.01) and lost TG after exercise (before vs 20 h after, P < 0.01). The observation that all the changes in lipoprotein concentration and composition reached their maximal differences compared to the pre-exercise values 20 h afterwards would support the assumption that circulating lipoproteins play an important role in the regeneration period, refilling the intramuscular triglyceride stores. PMID- 8354253 TI - Acute and delayed effects of prolonged exercise on serum lipoproteins. II. Concentration and composition of low-density lipoprotein subfractions and very low-density lipoproteins. AB - To investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, 13 healthy endurance-trained men were examined before and after (1 h, 20 h) a cross-country run [30 km, time: 130 (SD 7.4) min]. The data show that following acute exercise, serum triglyceride (TG) concentration were reduced (36%) as a consequence of a reduced number (31%) of very low density lipoprotein (VLDL) particles. Changes in composition of VLDL were present but less evident. In contrast to this, acute exercise did not induce significant changes in the average concentration of individual low-density lipoprotein (LDL) subfractions. However, changes in dense LDL [density (d) > 1.044 g.ml-1] concentration were significantly correlated to changes in serum TG: a reduction of dense LDL occurred in subjects with large reductions in serum TG. In addition, LDL composition changed significantly. Immediately (1 h) after exercise the TG content of all LDL subfractions was reduced. These reductions were significant in large (d = 1.006-1.037 g.ml-1) and small LDL (1.044-1.063 g.ml-1). It can be concluded therefore from our study that acute exercise primarily altered the composition of LDL subfractions while their concentration remained stable. PMID- 8354254 TI - Cardiac output in paraplegic subjects at high exercise intensities. AB - The purpose of this investigation was to compare cardiac output (Qc) in paraplegic subjects (P) with wheelchair-confined control subjects (C) at high intensities of arm exercise. At low and moderate exercise intensity Qc was the same at a given oxygen uptake (VO2) in P and C. A group of 11 athletic male P with complete spinal-cord lesions between T6 and T12 and a group of 5 well matched athletic male C performed maximal arm-cranking exercise and submaximal exercise at 50%, 70% and 80% of each individual's maximal power output (Wmax). Maximal VO2 (VO2max) was significantly lower, VO2max per kilogram body mass was equal and maximal heart rate (fc) was significantly higher in P compared to C. At VO2 of 1.3, 1.5 and 1.7 l.min-1, and for P 65%-90% of the VO2max, Qc was not significantly different between the groups, although, Qc in P was achieved with a significantly lower stroke volume (SV) and a significantly higher fc. Although the SV was lower in P, it followed the same pattern as SV in C during incremental exercise, i.e. an increase in SV until about 45% Wmax and thereafter a stable SV. The similar Qc at a given VO2 in both groups indicated that, even at high exercise intensities, circulation in P can be considered isokinetic with a complete compensation by fc for a lower SV. PMID- 8354255 TI - Regulation of local sweating in sleep-deprived exercising humans. AB - Thermoregulatory sweating [total body (msw,b), chest (msw,c) and thigh (msw,t) sweating], body temperatures [oesophageal (T(oes)) and mean skin temperature (Tsk)] and heart rate were investigated in five sleep-deprived subjects (kept awake for 27 h) while exercising on a cycle (45 min at approximately 50% maximal oxygen consumption) in moderate heat (T(air) and T(wall) at 35 degrees C). The msw,c and msw,t were measured under local thermal clamp (Tsk,l), set at 35.5 degrees C. After sleep deprivation, neither the levels of body temperatures (T(oes), Tsk) nor the levels of msw,b, msw,c or msw,t differed from control at rest or during exercise steady state. During the transient phase of exercise (when Tsk and Tsk,l were unvarying), the msw,c and msw,t changes were positively correlated with those of T(oes). The slopes of the msw,c versus T(oes) or msw,t versus T(oes) relationships remained unchanged between control and sleep-loss experiments. Thus the slopes of the local sweating versus T(oes) relationships (msw,c and msw,t sweating data pooled which reached 1.05 (SEM 0.14) mg.cm-2.min 1.degree C-1 and 1.14 (SEM 0.18) mg.cm-2.min-1.degree C-1 before and after sleep deprivation) respectively did not differ. However, in our experiment, sleep deprivation significantly increased the T(oes) threshold for the onset of both msw,c and msw,t (+0.3 degrees C, P < 0.001). From our investigations it would seem that the delayed core temperature for sweating onset in sleep-deprived humans, while exercising moderately in the heat, is likely to have been due to alterations occurring at the central level. PMID- 8354256 TI - A modified, local sweat collector for warm and humid conditions. AB - The purpose of this study was to modify a previously described local sweat collector to facilitate the investigation of sweat rate and composition in a warm (30 degrees C) and humid (relative humidity 80%) environment. The adherence of the collector to the skin was improved and a pouch was appended at the lower end of the collector. The limitations of the closed collector were examined by comparing the local sweat rate and the quantity of electrolyte excreted in sweat with those obtained using a second collector with a wide opening (to permit free evaporation) and by changes in the body mass. Eight subjects performed exercise on a cycle ergometer consisting of four equal periods of 15 min each, at 60% maximal oxygen consumption, with a rest of 5 min between each period. The sweat produced on a local skin area (85 cm2, upper posterior thorax region) was collected at the end of each period, before measuring the body mass on a sensitive (+/- 1 g) platform balance. The mean local sweat rate [2.61 (SEM 0.19) mg.cm-2.min-1] was 2.4 times greater than the pro-rated whole body mass loss but the two were strongly correlated (r = 0.82, P < 0.01). Compared to the open collector, the greater quantity of electrolyte excreted into the closed collector would suggest that the conditions which prevailed in the closed collector, such as a higher local skin temperature, may have affected the function of the sweat gland.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354257 TI - Does maximal neural activation of muscle increase after resistance training? PMID- 8354258 TI - The peripheral cholecystokinin receptors. PMID- 8354259 TI - Stereospecificity of the interaction of porcine pancreatic phospholipase A2 with micellar and monomeric inhibitors. A time-resolved fluorescence study of the tryptophan residue. AB - The binding effect of enantiomeric substrate analogs under micellar form on the local conformation and dynamics of the N-terminal region of porcine pancreas phospholipase A2 was examined by time-resolved fluorescence measurements of its single tryptophan residue (Trp3). The complexity of the fluorescence intensity decay of the unliganded protein (four excited-state lifetime populations) suggests a conformational heterogeneity of the N-terminal region of the protein. A considerable simplification of the excited-state lifetime profile was specifically observed in the complex with one of the stereoisomers [(R)-2 tetradecanoylamino)-hexanol-phosphocholine] at low inhibitor/protein molar ratio of approximately 9. This indicates the existence of a definite conformation of the N-terminal region of the protein in the complex. No effect was detected for the S-enantiomer. In parallel, the rotational mobility of the Trp residue in the complex with the R-enantiomer was reduced. At a higher inhibitor/protein molar ratio of approximately 130, the stereospecificity of the interaction was lost and complexes were formed with both stereoisomers. These complexes were, however, not similar to the specific one either in terms of the local Trp3 environment or of the volume of the rotating unit. The local effects of low amounts of monomeric inhibitors added to a preformed protein/micelle complex of a phospholipase A2 double mutant in which a Trp residue was genetically inserted near the active site at position 31 while the natural Trp3 was replaced by Phe [Kuipers, O., Vincent, M., Brochon, J. C., Verheij, H. M., de Haas, G. H. & Gallay, J. (1991) Biochemistry 30, 8771-8785], were also monitored by time-resolved fluorescence of this single Trp residue. A stereospecific dependence of the local perturbations was again observed. These results support the idea that the active conformation of the protein is reached in solution only after formation of a ternary complex: protein-interface-inhibitor. PMID- 8354260 TI - The glucagon-insulin antagonism in the regulation of cytosolic protein binding to the 3' end of phosphoenolpyruvate carboxykinase mRNA in cultured rat hepatocytes. Possible involvement in the stabilization of the mRNA. AB - Since protein binding to the 3' end of mRNA is believed to be involved in the control of mRNA stability, the time course of alterations in glucagon-induced phosphoenolpyruvate-carboxykinase-mRNA (PCK) levels, in the absence and presence of insulin, was correlated with the time course of changes in the binding of cytosolic protein from 24-h cultured rat hepatocytes to the 3' end of PCK mRNA. PCK-mRNA levels were monitored by Northern blot analysis and protein binding was analyzed by an electrophoretic mobility-shift assay. In 24-h cultured rat hepatocytes, binding of cytosolic protein to the PCK-mRNA 3' end and PCK-mRNA levels were increased to a transient maximum at 2 h and 2-4 h, respectively, by a 1-nM glucagon treatment, added with a change of medium. 100 nM insulin, added simultaneously with glucagon, reduced the glucagon-induced maximum of protein binding by 80% and the increase of PCK mRNA by about 30%. In controls without hormonal treatment protein binding at 1 h was also increased; this increase was prevented by insulin. 100 nM insulin, added 1 h after glucagon, reversed protein binding to the 3' end of PCK mRNA to nearly initial levels within 1 h and impaired the glucagon-induced increase in PCK-mRNA levels by 30%. The transcriptional inhibitor cordycepin, added 1 h after glucagon, did not prevent the further increase in glucagon-enhanced protein binding nor its reversal by insulin. It did, however, prevent a further significant increase in PCK mRNA. Hormonally regulated protein binding could be localized to the 256 distal bases of the PCK-mRNA 3' end. The proximal 466 bases of the PCK-mRNA 3' end as well as the 1050 bases of the histone-H1(0)-mRNA 3' end and the 1200 bases of the arylsulfatase-A-mRNA 3' end also bound cytosolic protein(s), but this protein binding was not altered by treatment with glucagon or insulin. The 3' end of PCK, arylsulfatase A and H1(0) mRNA exhibited strong binding of cytosolic protein(s) from diverse rat tissues such as heart, liver and lung as well as Fao rat hepatoma cells. Cytosolic protein(s) from spleen showed weak binding and proteins from HeLa and U937 tumor cells did not bind. Protein binding was most prominent with the 3' end of PCK mRNA and cytosolic extracts from liver.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8354262 TI - Isoforms of fatty-acid-binding protein in bovine heart are coded by distinct mRNA. AB - In the course of our studies on structure/function relationships of fatty-acid binding proteins, we reported earlier that the two isoforms of the 15-kDa cardiac fatty-acid-binding protein (cFABP) from bovine heart only differ in one position; Asn98 in pI 5.1-cFABP; Asp98 in pI 4.9-cFABP [Unterberg, C., Borchers, T., Hojrup, P., Knudsen, J. and Spener, F. (1990) J. Biol. Chem. 265, 16,255-16,261]. In the present study, we elucidate the origin for this heterogeneity. Isoelectric focusing analysis of immunoprecipitated in vitro translation products from total mRNA and positive-hybrid-selected cFABP/mRNA revealed two L-[35S]methionine labeled proteins corresponding to pI 5.1-cFABP and pI 4.9-cFABP. In a control experiment, recombinant mRNA derived from cDNA encoding pI 5.1-cFABP was translated and produced only pI 5.1-cFABP as shown by isoelectric focusing of the translation products. We could observe co-translational acetylation but not post translational deamidation of the cFABP isoforms. Taken together, our results demonstrate that the isoforms of cardiac fatty-acid-binding protein found in bovine heart are coded by distinct mRNA species. PMID- 8354261 TI - Tissue-dependent variation in the expression of elongation factor-1 alpha isoforms: isolation and characterisation of a cDNA encoding a novel variant of human elongation-factor 1 alpha. AB - A novel isoform of human elongation factor-1 alpha (EF-1 alpha 2) has been characterised. It shows a high similarity to other EF-1 alpha proteins, especially to a rat EF-1 alpha variant and it has all the characteristics of a functional EF-1 alpha protein. The pattern of expression of both EF-1 alpha 2 and EF-1 alpha was analysed in different human tissues. This showed that the two proteins were differentially expressed, EF-1 alpha 2 was expressed in brain, heart, skeletal muscle and in the transformed cell lines AMA and K14, but was undetectable in other tissues and in both primary and transformed human fibroblasts. EF-1 alpha was expressed in brain, placenta, lung, liver, kidney, pancreas and in all the cell lines that we have analysed but barely detectable in heart and skeletal muscle. PMID- 8354263 TI - Site specificity of glycation of horse liver alcohol dehydrogenase in vitro. AB - The site specificity of in vitro glycation of horse liver alcohol dehydrogenase (ADH) was examined and the results interpreted in terms of structural features of the enzyme molecule. In a phosphate buffer solution, glycation occurred at Lys231 (the main site of glycation in vivo), at Lys228 (which is not glycated in vivo), and at several unidentified positions. Buffer anions or NAD+ did not affect glycation of Lys231; this supported our hypothesis that the base catalyst which removes a proton from carbon 2 of a Lys231-attached aldimine is part of the ADH molecule [Shilton, B.H. & Walton, D.J. (1991) J. Biol. Chem. 266, 5587-5592]. Use of a molecular modelling programme indicated that this catalyst was likely to be the imidazole group of His348, exerting its effect through the hydroxyl of Thr347. Glycation of Lys228 occurred only in the presence of phosphate; in this case molecular modelling showed that the base catalyst could be a phosphate ion, bound to ADH at a positive region of the coenzyme binding site. NAD+ inhibited glycation of Lys228 by binding to the enzyme and restricting access to glucose. PMID- 8354264 TI - 1H- and 15N-NMR assignment and solution structure of the chemotactic Escherichia coli Che Y protein. AB - Che Y is a 129-residue parallel alpha/beta protein involved in bacterial chemotaxis. We have used this protein as a model to study the folding reaction of parallel alpha/beta proteins. As a first step we carried out the complete assignment of the 1H and 15N spectra from Escherichia coli Che Y protein on the basis of two-dimensional 1H homonuclear and 1H-15N heteronuclear experiments by using sequence-specific methods. Our assignments differ from the preliminary assignments made by Kar et al. [Kar, L., Matsumura, P. & Johnson, M.E. (1992) Biochem. J. 287, 521-531] of aromatic residues obtained by comparison of NOEs with short proton-proton distances in the crystal structure of Che Y. The analysis of the extension of the secondary elements, as well as a preliminary calculation of the three-dimensional structure, indicate that the solution structure is closely coincident with the single crystal structure determined by X ray diffraction. PMID- 8354265 TI - In vitro formation of a photoreversible adduct of phycocyanobilin and tobacco apophytochrome B. AB - The light-stable tobacco phytochrome apoprotein (PHYB) expressed in yeast can be assembled with phycocyanobilin to give a photoreversible adduct. The spectral properties of the reconstituted PHYB-phycocyanobilin species were determined by absorbacen and difference absorbance spectroscopies. The holoprotein exhibits absorbance maxima at 408 nm and 712 nm for the far-red-light-absorbing (Pfr) form and 356 nm and 658 nm for the red-light-absorbing (Pr) form. The ligation of the chromophores to the dimeric PHYB apoprotein resulted in a PHYB-phycocyanobilin adduct with the spectral properties of the Pr form. Kinetic analyses of the in vitro reconstitution for PHYB apoprotein under saturating concentrations of phycocyanobilin revealed a pseudo first-order rate constant of 2.8 x 10(-2)s.-1. The similarity with the reported rate constant for the reconstitution of light labile phytochrome (PHYA) from oat [Li, L. & Lagarias, J.C. (1992) Phytochrome assembly, J. Biol. Chem. 267, 19,204-19,210] suggests that the mechanisms of chromophore attachment are probably very similar for PHYA and PHYB. PMID- 8354266 TI - Involvement of the ADP/ATP carrier in permeabilization processes of the inner mitochondrial membrane. AB - The effect of different agents on inner-mitochondrial-membrane permeabilization and lipoperoxidation induced by Ca2+ and the pyridine-nucleotide oxidant t butylhydroperoxide or inorganic phosphate was investigated. Comparing the protection conferred by ADP, a substrate of the ADP/ATP carrier, dithiothreitol, a disulfide reductant and butylhydroxytoluene, a radical scavenger, it was found that ADP was always the most effective against mitochondrial damage, when present in the incubation medium from the beginning. Moreover, carboxyatractyloside, a specific inhibitor of the ADP/ATP carrier, abolished completely the protective effect of ADP on both the lipoperoxidation and mitochondrial swelling processes. Experiments where deenergized mitochondria were previously incubated with Ca2+ showed a decrease in the content of active ADP/ATP carrier, indicating a direct involvement of this protein in the formation of a non-specific Ca(2+)-dependent pore. Our results also eliminate the possibility of an attack of oxygen radicals on lipids or proteins of the mitochondrial membrane as the primary event triggering the permeability transition of the inner mitochondrial membrane. PMID- 8354267 TI - Abundance and subcellular distribution of GTP-binding proteins in 3T3-L1 cells before and after differentiation to the insulin-sensitive phenotype. AB - The abundance and the subcellular distribution of GTP-binding proteins was studied in membrane fractions (plasma membranes and low-density microsomes) from 3T3-L1 cells before and after differentiation to the insulin-sensitive phenotype. After differentiation, the abundance of alpha i (alpha subunit of GTP-binding protein Gi), alpha o (alpha subunit of GTP-binding protein G(o)), and of a 47-kDa alpha s (alpha subunit of GTP-binding protein Gs) as detected by immunoblotting with specific antisera was reduced by 10-50% when normalized per membrane protein. In contrast, a 43-kDa alpha s was increased about threefold after differentiation. Furthermore, cholera-toxin-catalyzed ADP-ribosylation of both 43 kDa and 47-kDa alpha s was disproportionately increased ninefold and threefold, respectively, possibly reflecting the increased production of an ADP-ribosylation factor in the differentiated cells. The small GTP-binding protein Ha-ras was reduced by 50%, whereas rab1 and other small GTP-binding proteins tentatively identified as rab-isoforms (ras-homologous gene products from brain) were increased by 100% and 70%, respectively. Since the total protein content of 3T3 L1 cells was increased threefold after differentiation, the observed increase of the 43-kDa alpha s, rab1 and of the other rab isoforms was eightfold, sixfold and fivefold, respectively, when normalized/cell count. With the exception of the rab isoforms, all GTP-binding proteins were predominantly, if not exclusively, located in the plasma membrane; comparable amounts of the rab isoforms were found in plasma membranes and low-density microsomes. Insulin induced the characteristic redistribution of glucose transporters GLUT4 from low-density microsomes to the plasma membranes, but failed to alter the subcellular distribution of any of the GTP-binding proteins investigated. These data suggest that the increase in the abundance of the 43-kDa alpha s subunit and of several rab isoforms might be related to specific functions of the adipocyte-like phenotype, but that none of the investigated guanine-nucleotide-binding regulatory (G)-proteins appears to be tightly associated with the GLUT4. PMID- 8354268 TI - Retrobiosynthetic analysis of carbon fixation in the phototrophic eubacterium Chloroflexus aurantiacus. AB - The phototrophic bacterium Chloroflexus aurantiacus does not use any of the known autotrophic CO2 fixation pathways. There is evidence for a new cyclic autotrophic pathway in which acetyl-CoA is converted to 3-hydroxypropionate and further to succinate and malate. This hypothesis was tested by feeding growing cultures during several generations with 3-hydroxy[1-13C]propionate, [1-13C]acetate, or [2 13C]acetate, in addition to unlabeled CO2. The relative 13C content of individual carbon atoms in biosynthetic amino acids and nucleosides was determined by 1H- and 13C-NMR spectroscopy. 13C coupling patterns were analyzed by two-dimensional 13C-TOCSY experiments which were optimized for the analysis of multiply 13C labeled biosynthetic samples. From the 13C enrichments of amino acids and nucleosides, the labeling patterns of central metabolic intermediates were evaluated by a retrobiosynthetic approach. Both 3-hydroxypropionate and acetate were incorporated into all central metabolic pools. The 13C labeling and coupling patterns suggest a novel carbon fixation pathway via 3-hydroxypropionate. Specifically, we propose that acetyl-CoA is carboxylated to malonyl-CoA which is reduced under formation of 3-hydroxypropionyl-CoA. Dehydration and reduction yield propionyl-CoA which is converted to succinate by a second carboxylation reaction. The net product of autotrophic carbon fixation appears to be glyoxylate. However, it is not yet known how glyoxylate is channeled into anabolic metabolism. Assimilation of acetate can proceed via the CO2 fixation pathway, but also via the glyoxylate pathway. PMID- 8354269 TI - Enzymes of a novel autotrophic CO2 fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle. AB - The phototrophic bacterium Chloroflexus aurantiacus can grow autotrophically but seems not to assimilate CO2 via any of the known autotrophic pathways. Holo [Holo, H. (1989) Arch. Microbiol. 151, 252-256] proposed a new pathway in which 3 hydroxypropionate is formed from acetyl-CoA. Previous studies excluded the operation of known CO2 fixation pathways and provided indirect evidence for the suggested pathway based on 13C-labelling experiments. Here all enzyme activities of the postulated cyclic CO2 fixation mechanism are demonstrated in vitro. In essence, acetyl-CoA is carboxylated and reductively converted via 3 hydroxypropionate to propionyl-CoA. Propionyl-CoA is carboxylated and converted via succinyl-CoA and CoA transfer to malyl-CoA. Malyl-CoA is cleaved to acetyl CoA and glyoxylate. Thereby, the first CO2 acceptor molecule acetyl-CoA is regenerated, completing the cycle and the net CO2 fixation product glyoxylate is released. This cycle represents the fourth autotrophic pathway in nature and is designated the 3-hydroxypropionate cycle. PMID- 8354270 TI - Molecular characterization of HES-2, a mammalian helix-loop-helix factor structurally related to Drosophila hairy and Enhancer of split. AB - Drosophila hairy (h) plays a crucial role in early development as a pair-rule segmentation gene. h and its structurally related gene Enhancer of split [E(spl)] are also required for normal sensory neurogenesis in late development. To analyze the molecular mechanisms of mammalian development, we recently characterized three rat helix-loop-helix (HLH) factors that show structural homology to the Drosophila h and E(spl) gene products, and found that rat factors exhibit distinct spatiotemporal expression patterns and act as a negative regulator. Here, we report the molecular characterization of another member of this family, designated HES-2. Rat HES-2 protein has a basic HLH domain homologous to h and E(spl) as well as the carboxy-terminal Trp-Arg-Pro-Trp sequence conserved among this family. The HES-2 mRNA is present as early as embryonic day 9.5 and is detected in a variety of tissues of both embryos and adults. DNase-I-footprinting analyses indicate that HES-2 binds to all E box sequences (CANNTG) we tested as well as to the N-box sequences (CACNAG). Further studies of gel-mobility-shift assays show that HES-2 has a higher affinity for the E box than for the N box. Transient transfection analyses suggest that HES-2 decreases the transcription originating from the promoters containing either the E box or the N box. These results indicate that HES-2 acts as a negative regulator through interaction with both E-box and N-box sequences. PMID- 8354271 TI - Folding and assembly of phage P22 tailspike endorhamnosidase lacking the N terminal, head-binding domain. AB - Tryptic digestion of a thermal unfolding intermediate of the phage P22 tailspike endorhamnosidase produces an N-terminally shortened protein fragment comprising amino-acid residues 108-666 [Chen, B.-L. & King, J. (1991) Biochemistry 30, 6260 6269]. In the present work, the 60-kDa C-terminal fragment was purified to homogeneity from the tryptic digest by gel-fitration chromatography. As in the case for the whole tailspike protein (72 kDa), the purified fragment was found to remain stably folded as a highly soluble, SDS-resistant, enzymatically active trimer. However, its unfolding in the presence of guanidinium chloride was accelerated at least 10-fold compared to the complete, native tailspike protein. Shortened tailspike trimers reconstituted spontaneously and with high yield after diluting a solution containing acid-urea-unfolded fragment polypeptides with neutral buffer. Upon recombinant expression of the 60-kDa polypeptide in Escherichia coli, it also assembled efficiently and formed SDS-resistant trimers. The refolding and assembly pathway of the N-terminally shortened tailspike paralleled that of the complete protein with slightly, but significantly, accelerated folding reactions, at both the subunit and the trimer levels. As found for the complete tailspike protein, yields of refolding and assembly of the 60-kDa fragments into SDS-resistant trimers decreased with increasing temperature. The refolding yield of fragments derived from a temperature sensitive mutant (Gly244-->Arg) tailspike protein was affected in similar fashion as shown for the whole protein. We conclude that the N-terminal domain (residues 1-107) is dispensable for folding and assembly of the P22 tailspike endorhamnosidase both in vitro and in vivo. PMID- 8354272 TI - Electrostatic evidence for the activation of the glutathione thiol by Tyr7 in pi class glutathione transferases. AB - A number of spectrophotometric studies [Graminski, G.F., Kubo, Y. & Armstrong, R.N. (1989) Biochemistry 28, 3562-3568; Liu, S., Zhang, P., Ji, X., Johnson, W.W., Gilliland, G.L. & Armstrong, R.N. (1992) J. Biol. Chem. 267, 4296-4299] have recently shown that the glutathione (GSH) thiol is deprotonated when it is in complex with glutathione S-transferase. Different models have been proposed for the activation of the glutathione S gamma, all pointing out the key role of active-site residue Tyr7. It remains unclear, however, how Tyr7 is actually involved in this process. In this paper we present an analysis of the electrostatic potential in the region of the active site of a pi-class GSH transferase. This analysis provides evidence that the titration behaviour of the absorption band of the E.GSH complex with a pK between 6 and 7 [Liu, S., Zhang, P., Ji, X., Johnson, W.W., Gilliland, G.L. & Armstrong, R.N. (1992) J. Biol. Chem. 267, 4296-4299] should rather be explained by the protonation/deprotonation equilibrium of Tyr7 than by the protonation/deprotonation equilibrium of the GSH thiol group itself. On the basis of this conclusion, a mechanism for activation of GSH is proposed: the Tyr7 OH group is deprotonated by the influence of the protein charge constellation and the peptide dipoles. Thus it acts as a general base, promotes proton abstraction from the GSH thiol and creates a thiolate anion with high nucleophilic reactivity. PMID- 8354273 TI - Estrogen-inducible pS2 protein is not the key regulatory component in the proliferation of human breast cancer cells (MCF-7). AB - Exposure of human breast cancer cells (MCF-7) to tumor promoters such as 12-O tetradecanoyl phorbol 13-acetate (TPA) for 24 h at concentrations of 1-100 nM resulted in marked inhibition of DNA synthesis but a 3-5-fold increase in the amount of pS2 protein in the medium. These results support our previous suggestion that pS2 protein is not involved in the mechanism controlling proliferation of MCF-7 cells. During treatment with TPA, the intracellular content of pS2 protein was constant, suggesting that TPA did not induce secretion of pS2 protein but rather de novo synthesis of the protein. The increase in the pS2 protein content of the medium by TPA was inhibited by simultaneous addition of cycloheximide, but not by that of actinomycin D. Northern-blot hybridization analysis showed that the amount of pS2 mRNA was unchanged by treatment of the cells with TPA. These results indicate that TPA does not induce transcription of the pS2 gene, and suggest that the main effect of TPA results from the induction of translation of pS2 mRNA. PMID- 8354274 TI - cDNA nucleotide sequence and primary structure of mouse uterine peptidylarginine deiminase. Detection of a 3'-untranslated nucleotide sequence common to the mRNA of transiently expressed genes and rapid turnover of this enzyme's mRNA in the estrous cycle. AB - Peptidylarginine deiminase is a protein-modulating enzyme which converts the arginine residues in proteins to citrulline residues. This study describes the complete primary structure of mouse peptidylarginine deiminase, which was deduced from nucleotide sequence analysis of cDNA clones plus proteochemical analysis of the purified enzyme. The composite cDNA sequence contained a 5' untranslated region of 7 bases, an open reading frame of 2019 bases that encoded 673 amino acids, a 3' untranslated region of 2662 bases, and part of a poly(A) tail. The N terminal and C-terminal sequences of the enzyme matched the sequences deduced from nucleotide analysis. Furthermore, we determined that the N-terminal sequence was N alpha-acetyl-Met-Gln-, a sequence which has never previously been reported among N alpha-acetyl-Met proteins. The Arg 352 of the enzyme was converted to a citrulline residue and the potential Asn-linked glycosylation site (Asn542-Glu543 Ser544) had no carbohydrate moiety. Thus, mouse peptidylarginine deiminase consists of 673 amino acids with a molecular mass of 76,260. Mouse peptidylarginine deiminase mRNA has two AU-rich structures in the 3' untranslated region which exhibit a high degree of similarity to those in lymphokine, cytokine and proto-oncogene mRNA species. Since the rat enzyme (previously reported) does not possess these characteristic structures, we compared the levels of enzyme activity and mRNA in the mouse and rat uterus at four defined phases of the estrous cycle. The degradation of peptidylarginine deiminase and its mRNA proceeded significantly faster in the mouse than in the rat. We speculate that the unusual structure of the mouse enzyme and its mRNA be involved in this species-specific rapid degradation. PMID- 8354275 TI - Purification and characterization of N-glycolyneuraminic-acid-specific lectin from Scylla serrata. AB - A sialic-acid-binding lectin with specificity for N-glycolylneuraminic acid (NeuGc) was purified from the hemolymph of the marine crab Scylla serrata by affinity chromatography using thyroglobulin-coupled agarose. The binding specificity of Scylla lectin distinguishes it from other known sialic-acid specific lectins found in Limulus polyphemus and Limax flavus, which show a broader range of specificity for sialic acids. The molecular mass of the purified lectin is about 55 kDa. Under reducing conditions (SDS/PAGE), it resolved into two subunits of 30 kDa and 25 kDa. NeuGc inhibited hemagglutination activity of the purified lectin at a concentration as low as 0.6 mM, whereas N acetylneuraminic acid (NeuAc) even at a concentration of 100 mM, failed to inhibit hemagglutination. This finding was supported by potent inhibition of hemagglutination by bovine and porcine thyroglobulins, which contain a NeuGc alpha 2-6Gal as terminal component of oligosaccharide residues. Neither glycoproteins (glycophorin NN; porcine submaxillary mucin), which contain NeuAc alpha 2-3Gal/GalNAc and NeuAc alpha 2-6GalNAc, nor human acid glycoprotein, which contains NeuAc alpha 2-3/alpha 2-6 Gal, or colominic acid, a sialopolymer with NeuAc alpha 2-8NeuAc, inhibited the lectin activity. The specificity of the lectin for NeuGc appears to account for the fact that it agglutinates rabbit and mice erythrocytes, but not human A, O, AB, rat or chicken erythrocytes, which contain NeuAc. The inability of the lectin to agglutinate erythrocytes (horse) that prominently express NeuGc could be due to O-acetylation of NeuGc. In support of this, bovine submaxillary mucin, which contains O-acetylated NeuGc inhibited the hemagglutination of the lectin better after removal of O-acetyl groups by base treatment. The unique specificity of Scylla lectin is of diagnostic potential for human cancer tissues expressing NeuGc, since NeuGc is not found in normal human tissues. PMID- 8354276 TI - Cholesterol 7 alpha-hydroxylase is up-regulated by the competitive inhibitor 7 oxocholesterol in rat liver. AB - Rats of the Sprague-Dawley strain were infused intravenously with a fat emulsion (Intralipid, trademark of Kabi Pharmacia, Uppsala, Sweden) containing 7 oxocholesterol. This resulted in an increased cholesterol 7 alpha-hydroxylase activity in liver microsomes as compared to controls and was accompanied by increased levels of cholesterol 7 alpha-hydroxylase mRNA and microsomal cholesterol 7 alpha-hydroxylase protein. Rats were also fed a cholestyramine supplemented diet and infused with 7-oxocholesterol. These animals excreted about half as much bile acids in faeces as cholestyramine-fed controls. Addition of 7 oxocholesterol to liver microsomes from normal rats in amounts corresponding to those present in microsomes from 7-oxocholesterol-treated rats inhibited the cholesterol 7 alpha-hydroxylase activity by about 75%. Cholesterol induced a type I binding spectrum when added to a purified bacterial-expressed cholesterol 7 alpha-hydroxylase (P-450c7 delta 2-24). 7-Oxocholesterol competitively inhibited the cholesterol binding spectrum, while 7 beta-hydroxycholesterol did not interfere with binding of cholesterol to the enzyme. It is concluded that treatment with the competitive inhibitor 7-oxocholesterol leads to a reduced bile acid biosynthesis and, as a consequence of reduced bile acid inhibition, a compensatory increase in cholesterol 7 alpha-hydroxylase synthesis. The high enzyme activity measured in microsomal preparations from 7-oxocholesterol-treated rats may be due to a continuous conversion of 7-oxocholesterol into less inhibitory metabolites, e.g. 7 beta-hydroxycholesterol. The latter compound was found in high concentrations in liver microsomes from rats treated with 7 oxocholesterol. The physiological importance of these results is discussed in relation to the previous findings that 7-oxocholesterol is accumulated in liver after cholesterol feeding and that 7-oxocholesterol is formed from cholesterol during lipid peroxidation. PMID- 8354277 TI - Transduction of reducing power across the plasma membrane by reduced glutathione. A 1H-NMR spin-echo study of intact human erythrocytes. AB - The NMR signal of reduced glutathione (GSH) was monitored in intact human erythrocytes by the 1H spin-echo Carr-Purcell-Meiboom-Gill pulse sequence. Addition of GSH, which was unable to cross the erythrocyte membrane, produced an approximate twofold increase of the GSH signal in glucose-depleted cells. Addition of oxidised glutathione (GSSG), did not affect the signal, and addition of GSH to hemolysates gave a much smaller increase. Reduction of internal GSSG by NADPH-dependent enzymes was excluded by experiments with glucose-supplied or glucose-6-phosphate dehydrogenase deficient cells. Involvement of external thiol groups of the erythrocyte membrane was shown by the lack of effect in cells treated with an impermeable thiol-blocking compound. Involvement of spectrin was indicated by the proportional loss of the effect in erythrocytes with variable genetic deficiency of spectrin. Protein-glutathione mixed disulfides appeared to be the source of the NMR response since an increase of their content, by diamide treatment or aging procedures, produced a higher GSH signal, while their reduction by permeable reductants gave the opposite effect. It is concluded that GSH can transduce its reducing power by a thiol/disulfide exchange mechanism that sequentially involves sulfur-rich proteins spanning across the erythrocyte membrane. PMID- 8354278 TI - Human alpha and beta parvalbumins. Structure and tissue-specific expression. AB - alpha and beta parvalbumins are Ca(2+)-binding proteins of the EF-hand type. We determined the protein sequence of human brain alpha parvalbumin by mass spectrometry and cloned human beta parvalbumin (or oncomodulin) from genomic DNA and preterm placental cDNA. beta parvalbumin differs in 54 positions from alpha parvalbumin and lacks the C-terminal amino acid 109. From MS analyses of alpha and beta parvalbumins we conclude that parvalbumins generally lack posttranslational modifications. alpha and beta parvalbumins were differently expressed in human tissues when analyzed by immunoblotting and polymerase-chain reaction techniques. Whereas alpha parvalbumin was found in a number of adult human tissues, beta parvalbumin was restricted to preterm placenta. The pattern of alpha parvalbumin expression also differs in man compared to other vertebrates. For example, in rat, alpha parvalbumin was found in extrafusal and intrafusal skeletal-muscle fibres whereas, in man, alpha parvalbumin was restricted to the muscle spindles. Different functions for alpha and beta parvalbumins are discussed. PMID- 8354279 TI - Subunit composition, crystallization and preliminary crystallographic studies of the Desulfovibrio gigas aldehyde oxidoreductase containing molybdenum and [2Fe 2S] centers. AB - The Desulfovibrio gigas aldehyde oxidoreductase contains molybdenum bound to a pterin cofactor and [2Fe-2S] centers. The enzyme was characterized by SDS/PAGE, gel-filtration and analytical ultracentrifugation experiments. It was crystallized at 4 degrees C, pH 7.2, using isopropanol and MgCl2 as precipitants. The crystals diffract beyond 0.3-nm (3.0-A) resolution and belong to space group P6(1)22 or its enantiomorph, with cell dimensions a = b = 14.45 nm and c = 16.32 nm. There is one subunit/asymmetric unit which gives a packing density of 2.5 x 10(-3) nm3/Da (2.5 A3/Da), consistent with the experimental crystal density, rho = 1.14 g/cm3. One dimer (approximately 2 x 100 kDa) is located on a crystallographic twofold axis. PMID- 8354280 TI - Sequence of extracellular mouse protein BM-90/fibulin and its calcium-dependent binding to other basement-membrane ligands. AB - Partial sequence comparisons have recently indicated that two extracellular components, fibulin from human placenta and BM-90 from a basement-membrane producing mouse tumor, are either identical or closely related proteins. In this study, a complete sequence analysis of mouse BM-90 cDNA showed a 539-residue N terminal core structure (domains I and II), which was 85% identical with the same core structure of human fibulin. A 137-residue C-terminal sequence (domain III) was unique for BM-90 and could also be identified by Edman degradation. This suggested a novel splice product, variant D, which is characteristic for the mouse tumor. A second 117-residue C-terminal sequence (domain III) was identified in additional mouse cDNA clones and showed 91% identity with the region specific for variant C of fibulin. Northern blots using mouse cells demonstrated two mRNA species, 2.7 kb and 2.3 kb, which encoded the variants D and C, respectively. The sequence of BM-90/fibulin indicates the presence of nine epidermal-growth-factor like repeats in the core domain-II structure, eight of which contain consensus motifs for calcium binding. This binding is apparently important for the interaction of BM-90 with laminin and nidogen and for some weaker interactions with collagen IV. Further binding of BM-90 was demonstrated to fibronectin and BM 90 itself, but did not depend on calcium. Major binding sites for BM-90 were identified at a C-terminal segment of laminin A chain and at the N-terminus of nidogen. The broad interaction repertoire of BM-90 is comparable to that of nidogen and both proteins may have similar roles as connecting elements in the extracellular matrix. PMID- 8354281 TI - Multiphasic denaturation of glutathione transferase B1-1 by guanidinium chloride. Role of the dimeric structure on the flexibility of the active site. AB - The unfolding and refolding mechanisms of dimeric glutathione transferase GSTB1-1 from Proteus mirabilis, using guanidinium chloride as a denaturant, have been investigated. The protein transitions were monitored by enzyme activity, intrinsic fluorescence, far ultraviolet circular dichroism and gel-filtration chromatography. The non coincidence of denaturation curves at equilibrium indicates that the unfolding of GSTB1-1 is a multistep process, i. e. inactivation of the structured dimer, dissociation into partially structured monomers followed by complete unfolding. In the 50% inactivated enzyme the Km for glutathione increases threefold, while the kcat appears almost the same, indicating that the initial phase of the denaturation involves the binding site of glutathione. The rapid recovery of the folded dimer precedes the complete enzyme reactivation. This indicates that the reconstitution of the native structure of GSTB1-1 is the result of folding and association of compact monomers followed by subtle rearrangements of assembled monomers that build up the active site. PMID- 8354282 TI - Purification and characterisation of D-glucose oxidase from white-rot fungus Pleurotus ostreatus. AB - D-Glucose oxidase was purified 27.5-fold to apparent homogeneity with an overall yield of 23.8%, from Pleurotus ostreatus, through a purification procedure of ammonium sulphate precipitation, gel-permeation, anion-exchange and hydrophobic interaction chromatography. The molecular mass determined by gel filtration was found to be 290 kDa. SDS/PAGE revealed that the enzyme consists of four subunits with a molecular mass of 70 kDa. The absorption spectra of the enzyme exhibit maxima at 280, 360 and 460 nm. The enzyme shows a fluorescence spectrum with an excitation maximum at 470 nm and an emission maximum at 530 nm. These results indicate that the prosthetic group of the enzyme is flavin and that the enzyme contains 4 mol flavin/mol enzyme. The enzyme is optimally active at 50 degrees C and at pH 5.5-6.0. It exhibits broad affinity for various sugars and specificity for D-glucose with Km value of 1.34 mM. 2,6-Dichloroindophenol, Wurster's blue, and 4-benzoquinone can function as electron acceptors but phenazine methosulphate cannot function as an electron acceptor. The enzyme is inhibited completely by mercuric chloride and partially by silver sulphate, sodium azide 8 hydroxyquinoline. PMID- 8354283 TI - Feedback regulation of mammalian ornithine decarboxylase. Studies using a transient expression system. AB - Ornithine decarboxylase catalyzes the first step in the biosynthesis of polyamines in mammalian cells. The enzyme is subject to various control mechanisms to maintain adequate intracellular levels of polyamines. Polyamines exert a strong feedback control on ornithine decarboxylase. In a recent study [van Daalen Wetters, T., Macrae, M., Brabant, M., Sittler, A. & Coffino, P. (1989) Mol. Cell. Biol. 9, 5484-5490], it was concluded that feedback control of ornithine decarboxylase is mainly, if not exclusively, a posttranslational phenomenon. The existence of a fast-acting polyamine-stimulated component of ornithine decarboxylase degradation that acts on newly synthesized monomeric forms of the enzyme was postulated. In the present study we have used a transient expression system to test this hypothesis. The expression of ornithine decarboxylase in mock-transfected COS cells varied depending on the cellular supply of polyamines as has been found in other mammalian cells. Thus, supplementing the cells with exogenous spermidine resulted in a marked decrease in ornithine decarboxylase activity, whereas depletion of intracellular polyamines, using an ornithine decarboxylase inhibitor, gave a large increase in the cellular content of the enzyme. COS cells expressing an ornithine decarboxylase mRNA devoid of its 5' non-translated region did not exhibit any feedback control of the enzyme, neither in the presence of exogenous spermidine nor when the intracellular polyamine levels were depleted to the same extent as in the mock-transfected COS cells. The results strongly suggest that the feedback control of ornithine decarboxylase is not merely a posttranslational phenomenon. PMID- 8354284 TI - Reaction of imidazole-citrate-deformed glycogen phosphorylase with amino acids. AB - Incubation of phosphorylase with L-valine in the presence of 0.4 M imidazole citrate results in a time-dependent decrease in the absorption of the enzyme bound cofactor pyridoxal 5'-phosphate at 333 nm and the generation of a new absorption maximum at 415 nm which appears to be due to an enzyme-bound coenzyme amino-acid aldimine adduct. Consequently, the enzyme is inactivated to less than 10% of its initial activity. The formation of the adduct of phosphorylase b with L-valine (0.1 M) proceeds with t1/2 approximately 8 min at pH 6.8 and 25 degrees C and is slightly inhibited by AMP. Phosphorylase a reacts five times more slowly than phosphorylase b. The decrease in enzymic activity is linked to the formation of the coenzyme-amino-acid adduct and is not due to resolution of the enzyme. Both the original absorption spectrum and phosphorylase activity are restored by gel filtration in the absence of L-valine and imidazole citrate. Similar reactions occur with other L-amino acids, an exception being L-cysteine which leads to resolution of the enzyme [Shaltiel, S., Hedrick, J. L. & Fischer, E. H. (1966) Biochemistry 5, 2108-2116]. No reaction is observed with D-amino acids or in the absence of imidazole citrate. Pyridoxal-reconstituted phosphorylase rapidly produces with amino acids not only the aldimine adduct but also a species absorbing at 318 nm. Enzyme-bound pyridoxal 5'-phosphate and pyridoxal exhibit a positive CD signal in the region of 333 nm; in contrast, the absorption bands of the coenzyme-amino-acid adducts at 415 nm and 318 nm are optically inactive. Neither pyridoxal-5'-phosphate-reconstituted nor pyridoxal-reconstituted phosphorylase in imidazole citrate catalyses any of the common pyridoxal-5' phosphate-mediated reactions of amino acids, e.g. transamination, decarboxylation or racemization, thus testifying to the high degree of reaction specificity of phosphorylase. PMID- 8354285 TI - Identification and analysis of a matrix-attachment region 5' of the rat glutamate dehydrogenase-encoding gene. AB - Eukaryotic chromatin is thought to be organized into independently regulated loop domains by interaction of matrix-attachment regions (MAR) of the DNA to the nuclear matrix. To define the borders of the chromatin loop containing the glutamate dehydrogenase (GDH) gene, we screened the GDH gene and flanking regions for the presence of MAR sequences. We here report identification, mapping and sequencing of an (A + T)-rich MAR located 2010-1397 bp upstream of the transcription initiation site of GDH, that mediates strong binding to the nuclear matrix. Smaller regions can also confer binding capacity, although at a lower affinity. This (A + T)-rich MAR contained 11 bp and 12 bp (A + T)-rich direct repeats, but not any of the sequences previously described to be associated with MAR activity. We here show that the presence of (A + T)-rich domains of DNA is not sufficient to confer binding capacity, since (A + T)-rich sequences located downstream of the identified MAR did not bind to the nuclear matrix. Moreover, a consensus topoisomerase-II-binding site located downstream of the MAR was found to be insufficient to mediate substantial binding. The number of binding sites in the nuclear matrix for MAR-containing fragments was shown to be approximately 15,000/nucleus. Since organization of the entire rat genome in loops with an average loop size of 100 kbp would require 60,000 binding sites, this suggests that only part of the genome is organized in loops. Alternatively, we might have underestimated the number of binding sites. The GDH MAR, and MAR-containing fragments derived from other species, were found to bind to the same binding sites in the nuclear matrix, although the affinity varied. PMID- 8354286 TI - Structural similarity between lung surfactant protein D and conglutinin. Two distinct, C-type lectins containing collagen-like sequences. AB - Preparations of bovine lung surfactant D (SP-D) and conglutinin were examined by electron microscopy, gel-filtration and SDS/PAGE. SP-D is composed of non covalently linked subunits, of 160 kDa, which each contain three, disulphide linked, 44-kDa polypeptide chains. In the electron microscope a single 160-kDa subunit of SP-D appears as a 45.8 +/- 3-nm-long rod connected to a small globular 'head'. Particles were also seen which correspond to non-covalently linked dimers, trimers and tetramers of the 160-kDa monomer subunit of SP-D. The tetramer structure contains 12 polypeptide chains and is very similar to the electron microscopy images and model reported by Strang et al. [Strang, C. J., Slayter, US., Lachmann, P. J. and Davis, A. E. (1986) Biochem. J. 236, 3811-389] for bovine conglutinin in which four 160-kDa subunits are disulphide-linked to give a molecule of expected molecular mass of 528 kDa. This study confirmed the findings by Strang et al. in the above paper for intact conglutinin and also emphasised that the rod-like structures, of length 37.6 +/- 3.7 nm, seen in the conglutinin subunits were significantly shorter than those in SP-D despite the close similarity in amino acid sequence (79% identify) and chain length between the two proteins. In addition, a truncated form of conglutinin was found in the conglutinin preparations, due to limited proteolysis of the Arg-Ala bond at position 54 in the 44-kDa chains. These truncated conglutinin chains yield a subunit composed of three shortened, non-disulphide-linked, chains and this subunit appears as a monomer with a rod length of 34.2 +/- 2.8 nm in the electron microscope. On gel-filtration, a proportion of the SP-D preparation behaved, as expected, as a molecule with an apparent molecular mass of 600 kDa. The remainder of the SP-D preparation behaved as aggregated material with a molecular mass greater than 900 kDa which yielded no distinct structures in the electron microscope. Intact conglutinin was eluted at a position greater than 900 kDa but yet provided clear electron microscopy images of the tetramer structure described above.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8354287 TI - Pigments induce folding of light-harvesting chlorophyll a/b-binding protein. AB - The conformational behaviour of the light-harvesting chlorophyll a/b-binding protein (LHCP), the apoprotein of the major light-harvesting complex (LHCII) of photosystem II in plants, has been studied. According to the circular dichroism in the ultraviolet range measured with isolated LHCII, the protein in the complex adopts a folded structure with a high content of alpha helix (about 60%), whereas the non-pigmented, solubilized protein has a less ordered structure (about 20% alpha helix). LHCP-pigment complexes that have been reconstituted from the overexpressed protein and isolated pigments in the presence of detergents display a protein CD signal similar to that of authentic LHCII, indicating that LHCP folds into the native structure during the reconstitution procedure. Renaturation of LHCP in these experiments is dependent on the presence of pigments and the formation of stable LHCP-pigment complexes. Pigment-induced engagement of LHCP in a compact structure has also been shown by two additional experimental approaches. (a) Upon complex formation, LHCP or its precursor (pLHCP) becomes resistant to trypsin digestion with the exception of an N-terminal segment of the protein; the same protection of LHCP is known to occur in intact thylakoids. (b) Pigment binding renders a cysteine residue within the N-proximal hydrophobic domain of the protein as well as a newly introduced cysteine four amino acid positions from the C terminus inaccessible to modification with a sulfhydryl specific label whereas the N terminus stays susceptible to specific labelling. These observations support the notion that only the N terminus protrudes from a compact protein-pigment structure in LHCII. The fact that the major part of LHCP is trypsin-resistant in pigmented complexes reconstituted in the absence of a membrane or even lipids justifies caution in using protection against trypsin as a criterion for the integration of LHCP into the thylakoid membrane. PMID- 8354288 TI - Inactivation of interleukin-6 in vitro by monoblastic U937 cell plasma membranes involves both protease and peptidyl-transferase activities. AB - Human promonocytic U937 cells have previously been shown to possess at their cell surface specific transmembrane serine proteases and N-terminal amino acid proteases as well as associated enzymes including elastase and cathepsin G. In this study, purified plasma membranes from U937 cells are reported to degrade the recombinant 21-kDa 125I-interleukin-6 (125I-IL-6) into 8-kDa products with loss of biological activity, as monitored by polyacrylamide gel electrophoresis and a cell-proliferation bioassay. Degradation of 125I-IL-6 by plasma membranes was completely prevented by the serine-protease inhibitor diisopropyl fluorophosphate, but was only partially impaired by alpha 1-protease inhibitor and antibody against cathepsin G. A similar incubation of 125I-IL-6 with cathepsin G purified from U937 cells caused hydrolysis of the cytokine into similar inactive 8-kDa fragments, whereas incubation with purified U937 cell elastase failed to degrade the peptide. These findings indicate that U937 cells hydrolyze IL-6 using cell-associated serine-protease activity and that cathepsin G partially participates in this degradation. Prolonged incubation of 8-kDa 125I IL-6 fragments with purified U937 plasma membranes, led to a complete loss of IL 6 activity related to the transformation of the 8-kDa forms into a higher molecular-mass complex (16 kDa). This complex was stable in SDS and 2 mercaptoethanol at 100 degrees C and was not dissociated by hydroxylamine treatment, indicating the formation of a covalent non-ester bond between the 8 kDa 125I-IL-6-derived peptide and an undetermined acceptor. An initial oxidative treatment of 125I-IL-6 partially prevented complex formation, suggesting the presence of one or more oxidizable methionine residues at the binding site of 8 kDa 125I-IL-6 peptide. The kinetics of complex formation (time dependence and plasma-membrane-concentration dependence), as well as its inhibition by a specific inhibitor of N-amino-peptidase activity, bestatin, suggest the participation of peptidyl-transferase activity in complex formation. Finally, a plasma-membrane fraction, corresponding to a molecular mass > or = 30 kDa, was able to convert the 8-kDa 125I-IL-6 forms into the 125I-labeled 16-kDa complex, suggesting that a > or = 30-kDa peptidyl-transferase enzyme catalyzes the reaction and provides the 125I-labeled 16-kDa peptide by dimerization of 8-kDa 125I-IL-6-derived intermediates. Further identification of the plasma-membrane associated peptidyl transferase as a regulator of IL-6 proteolysis may be of physiological relevance for the control of IL-6 biological activity. PMID- 8354289 TI - Protein O-mannosylation in Candida albicans. Determination of the amino acid sequences of peptide acceptors for protein O-mannosyltransferase. AB - A protein-O-D-mannosyltransferase (PMT) assay was optimised using a microsomal membrane preparation from Candida albicans and a peptide acceptor, YNPTSV. [14C]Mannose was transferred from dolichyl phosphate [14C]mannose to the threonine or serine residues of the peptide. During the assay, the peptide was highly susceptible to proteolysis. A blocked peptide Ac-YNPTSV-NH2 was resistant to proteolysis and was apparently a better acceptor for O-mannosylation. This peptide had a Km value of 4.3 mM in the assay. A number of other peptides were tested with altered sequences. Maximum incorporation of [14C]mannose was obtained with a pentapeptide YATAV (Km 2.2 mM) which was further improved by blocking both ends: Ac-YATAV-NH2 (Km 0.25 mM). Finally, and unexpectedly, an improvement was noted if the acetyl group on the N terminus was replaced by a biotin residue. Biotin-YATAV-NH2 had a Km of 0.075 mM. The biotin residue may be important in increasing the lipophilicity of the peptide and thus aid its adhesion to the Candida membranes. The simplest peptide that could act as an efficient mannose acceptor was Ac-ATA-NH2, whilst no incorporation was observed with Ac-GTG-NH2. PMID- 8354290 TI - Teichoic acid and lipoteichoic acid of Streptococcus pneumoniae possess identical chain structures. A reinvestigation of teichoid acid (C polysaccharide). AB - Teichoic acid (C polysaccharide) was extracted and purified from Streptococcus pneumoniae R6 with standard procedures except that lipoteichoic acid was extracted first. The dephosphorylated repeating unit was isolated after hydrolysis with 48% (by mass) HF, the bis(phosphocholine)-containing repeating unit was isolated by alkali hydrolysis, anion-exchange chromatography and phosphomonoester cleavage. On the basis of compositional analysis, fast-atom bombardment mass spectrometry and NMR spectroscopy the following structure is proposed: [formula: see text] where AATGal is 2-acetamido-4-amino-2,4,6-trideoxy D-galactose. The repeating units are linked to each other by phosphodiester bonds between O5 of the ribitol and O6 of the glucopyranosyl residue of adjacent units. This chain structure is identical with that previously established for pneumococcal lipoteichoic acid [Behr, T., Fischer, W., Peter-Katalinic, J. & Egge, H. (1992) Eur. J. Biochem. 207, 1063-1075]. This represents a unique situation because in other Gram-positive bacteria teichoic and lipoteichoic acids are structurally unrelated. PMID- 8354291 TI - Structures of the glycopeptidolipid antigens of two animal pathogens: Mycobacterium senegalense and Mycobacterium porcinum. AB - The structures of the major glycolipid antigens of two animal pathogens Mycobacterium senegalense and Mycobacterium porcinum were elucidated by a combination of fast-atom bombardment mass spectrometry, nuclear magnetic resonance spectroscopy, chemical analyses and radiolabeling experiments. Five glycoconjugates belonging to the class of C-mycoside glycopeptidolipids were characterized in each species. They shared with those recently described in M. peregrinum the same unusual distribution of the disaccharides on the alaninol end of the molecules. Both species showed the presence of the novel sulfated glycopeptidolipid. In addition, some acetylated forms of the glycolipids were also present in the species examined. Identical seroreactivities were observed between the glycolipid antigens extracted from M. senegalense, M. porcinum and M. peregrinum and an antiserum raised against the whole lipid antigens of M. peregrinum. These data reinforce the close taxonomic relationships between the three mycobacterial species and demonstrate the antigenicity of the new variants of mycobacterial glycopeptidolipids. PMID- 8354292 TI - Effect of cell attachment and growth on the synthesis and fate of dolichol-linked oligosaccharides in Chinese hamster ovary cells. AB - The inhibition of cellular processes in suspended anchorage-dependent Chinese hamster ovary (CHO) cell lines and their restoration upon attachment to a solid substrate has been used as a model to study the relationship between oligosaccharide-diphospho-dolichols and their metabolic products (glycoprotein and soluble oligosaccharide material, i.e. oligosaccharide phosphates and neutral oligosaccharides). Using metabolic labelling we demonstrated that suspended cells have a low incorporation rate into lipid intermediates and into glycoproteins. The oligosaccharide-lipid populations are mainly glucosylated and the neutral oligosaccharides have exclusively a chitobiosyl residue at their reducing end. In contrast, monolayer cells exhibit a high incorporation rate into lipid intermediates with a pattern dominated by two species containing either two or five mannose residues, and into glycoproteins with a pattern similar to the one observed for suspended cells (i.e. glucosylated species). In monolayer cells the neutral oligosaccharides possess either one or two GlcNAc residues at their reducing end. The variations in the nature and in the quantity of soluble oligosaccharide material as a function of the cell density reflects regulatory points in the synthesis of N-glycosyl proteins. The first regulatory point could be the control of the quantity of non-glucosylated oligosaccharide-lipids to be channelled toward the glucosylated lipid-donor pool. The level of this donor pool being constant, the oligosaccharide-transferase could utilize oligosaccharide lipid donors at a constant rate by two different reactions: either transfer onto protein when acceptors are available, or transfer onto water generating neutral oligosaccharides possessing two GlcNAc residues at the reducing end. Another regulatory point would be the degradation of a part of neoglycoproteins leading to the release of neutral oligosaccharides possessing one GlcNAc residue at the reducing end. PMID- 8354293 TI - Glucose administration induces the premature expression of liver glucokinase gene in newborn rats. Relation with DNase-I-hypersensitive sites. AB - Glucokinase first appears in the liver of the rat 2 weeks after birth and its activity rapidly increases after weaning on to a high-carbohydrate diet. The appearance of glucokinase is principally due to the increase of plasma insulin and to the decrease of plasma glucagon concentrations. Oral glucose administration to 1- or 10-day-old suckling rats induced an increase in plasma insulin and a fall in plasma glucagon and allowed a rapid accumulation of liver glucokinase mRNA, secondarily to a stimulation of gene transcription. When unrestrained late pregnant rats were infused with glucose during 36 h to induce an increase in fetal plasma insulin and a decrease in fetal plasma glucagon concentrations, glucokinase mRNA was detectable in fetal liver but the level was 100-fold lower than that observed in 1- or 10-day-old suckling rats. It is suggested that the hormonal environment did not allow glucokinase gene expression to be induced in fetal liver and that the absence of expression of glucokinase in suckling rat liver is due to the presence of low plasma insulin and high plasma glucagon levels. The chromatin structure of the glucokinase gene was examined during development by identification of DNase-I-hypersensitive sites from the region comprised between -8 kb upstream and +4 kb downstream of the cap site. Five hypersensitive sites were found: four liver-specific sites upstream of the cap site and one non-specific site in the first intron. These sites are already present in term fetus but the intensity of the two proximal sites located upstream of the cap site increase markedly after birth. This suggests that these sites could be implicated in the regulation of glucokinase gene expression by insulin and glucagon. Full DNase-I-hypersensitivity of these two proximal sites seems necessary for the mature response of glucokinase gene in response to changes in pancreatic hormones concentrations. PMID- 8354294 TI - Properties of some nuclear nucleases of rat thymocytes and their changes in radiation-induced apoptosis. AB - Three nuclease activities have been found and characterized in rat thymocyte nuclear extracts. A Mn(2+)-dependent nuclease is loosely bound to nuclear components and can be extracted with 0.35 M NaCl. The enzyme is activated by Mn2+ but not by Mg2+, Ca2+, or both. Its molecular mass is 36-40 kDa when measured by gel filtration and 37 kDa by SDS/PAGE. An acidic nuclease is independent of divalent ions, produces DNA strand breaks with 5'-OH ends, its molecular mass is about 37 kDa. Two fractions of Ca2+/Mn(2+)-dependent nuclease, differing in binding to CM-Sepharose but identical in other respects, are active in the presence of Mn2+ but can be additionally activated by Ca2+. They are inactive in the presence of Mg2+ or Ca2+ but cleave DNA in Ca2+/Mg(2+)-containing medium. The molecular mass of the enzyme is 22 kDa as determined by both gel filtration and electrophoresis. The dependence of nuclease activities on pH, ions, and sulfhydryl reagents is described. Cycloheximide injection to both control and irradiated animals strongly inhibits the activities of Ca2+/Mn(2+)-dependent nuclease from thymocyte nuclei separated by chromatography on CM-Sepharose and does not change the activities of Mn(2+)-dependent and acidic nucleases. Nuclease activity in thymocyte nuclei from irradiated rats is increased in Ca2+/Mg(2+) containing and Ca2+/Mn(2+)-containing media whereas there is no change in the activity of acidic nuclease. Ca2+/Mn(2+)-dependent nuclease is extracted from thymocyte nuclei of irradiated rats with 0.35 M NaCl but from control nuclei only with 0.5 M NaCl. Possible reasons of labilization of Ca2+/Mn(2+)-dependent nuclease binding to the nuclear structures in dying thymocytes are discussed. PMID- 8354295 TI - Ciprofibrate, a carcinogenic peroxisome proliferator, increases the phosphorylation of epidermal-growth-factor receptor in isolated rat hepatocytes. AB - Ciprofibrate, a hypolipidaemic drug with carcinogenic and peroxisome proliferation effects in rat liver, was found to increase the phosphorylation of epidermal-growth-factor receptor in 32P-labeled isolated rat hepatocytes. This effect was suppressed by protein-kinase-C inhibitors, and was accompanied by an almost complete inhibition of the receptor autophosphorylation normally induced by its ligand. However, in vitro experiments showed that protein-kinase-C phosphorylation of purified epidermal-growth-factor receptor was activated by ciprofibroyl-CoA, the acyl-CoA derivative of the drug, but not by the unmodified drug. Neither compound affected the ligand induction of epidermal-growth-factor receptor autophosphorylation in isolated liver membranes. These results suggest that metabolically produced ciprofibroyl-CoA in liver cells would activate protein-kinase-C and produce changes in epidermal-growth-factor-receptor function. PMID- 8354296 TI - Evaluation of amoxicillin clavulanate twice daily versus thrice daily in the treatment of otitis media in children. Danish-Swedish Study Group. AB - A total of 311 children who had recurrent otitis media or who had experienced failure of initial treatment of acute otitis media with phenoxymethylpenicillin, amoxicillin, ampicillin esters or cefaclor were entered into a single-blind study in two parallel groups in order to compare the clinical efficacy and safety of amoxicillin/clavulanate suspension given b.i.d. or t.i.d. for seven days. The patients were examined prior to the start of treatment, at an early follow-up visit 9 to 12 days after the start of treatment and at a late follow-up visit about three weeks later. Specimens for bacteriological culture were taken from the nasopharynx at entry, at the early follow-up visit, and at the late follow-up visit if there were symptoms of otitis. Both treatment groups showed a similar response, 90% or more of the patients being cured or showing improvement at the time of the early follow-up visit. The initial nasopharyngeal cultures showed growth of Haemophilus influenzae in 53% of the patients, Moraxella catarrhalis in 43% and Streptococcus pneumoniae in 39%. After treatment, cultures showed elimination of the initial pathogens in 30% of patients in both groups and recolonization in 23% in both groups. Haemophilus influenzae was the bacteria most frequently found in the nasopharynx at the first follow-up visit. Adverse effects, which consisted mostly of gastrointestinal and dermatological reactions, tended to be more common in the b.i.d. group but the difference was not statistically significant. PMID- 8354297 TI - Efficacy of pyrimethamine/sulfadoxine in the prevention of toxoplasmic encephalitis relapses and Pneumocystis carinii pneumonia in HIV-infected patients. AB - The efficacy and safety of 25 mg pyrimethamine plus 500 mg sulfadoxine given twice a week in preventing relapses of AIDS-related toxoplasmic encephalitis was evaluated in an open study. The 56 HIV-infected patients evaluated had responded to intensive treatment with pyrimethamine/clindamycin prior to starting the present prophylactic regimen. Four patients (7 %) experienced relapse while on pyrimethamine/sulfadoxine. The probability of freedom from relapse was > 90% for 12 months and > 80% for 24 months. Side effects comprised mild or moderate allergic reactions which occurred in 23 patients (41 %), leading to discontinuation in four patients (7%). Forty-nine of the 56 patients did not have a history of Pneumocystis carinii pneumonia and did not receive antiparasitic prophylaxis other than pyrimethamine/sulfadoxine; two of them (4 %) developed pneumocystosis. The probability of freedom from pneumocystosis was about 90 % for 24 months. Pyrimethamine/sulfadoxine twice a week appears to be a promising regimen for prevention of toxoplasmic encephalitis, and also appears to provide protection against Pneumocystis carinii pneumonia. Although allergic reactions are usually mild and disappear on continuation, they may limit the value of this regimen. PMID- 8354298 TI - Determination of serum arabinitol levels by mass spectrometry in patients with postoperative candidiasis. AB - A combined gas chromatography-mass spectrometry (GC-MS) technique was used for serial determination of serum arabinitol levels in patients with postoperative candidiasis. Forty subjects were investigated, 18 patients with candidiasis, 7 patients with superficial Candida colonization and 15 postoperative control patients. The arabinitol levels were highly elevated, slightly elevated and normal in 13, 1 and 4 patients respectively with candidiasis; in 2, 2 and 3 colonized patients and in 1, 1 and 13 control patients (p < 0.001, chi 2, between all the groups). The sensitivity of a single arabinitol determination for detection of postoperative candidiasis was 27.6 % and the specificity 89.2 %. Use of multiple samples improved sensitivity up to 72.2% per patient (123 samples) with a specificity of 86.4 %. Highly elevated arabinitol concentrations were detected in only one patient before the onset of therapy. Determination of arabinitol levels by GC-MS is a specific test for diagnosing candidiasis, but multiple samples are required for adequate sensitivity, and the initiation of therapy must still be on an empirical basis. PMID- 8354299 TI - Evaluation of five commercial antifungal susceptibility testing systems. AB - Five commercial antifungal susceptibility testing systems were studied for repeatability and reproducibility as well as concordance of results with the MICs for ten reference strains belonging to six different species. Repeatability was determined by testing each strain in triplicate on the same day, and reproducibility by repeating this triple determination on three different days. On the basis of 630 yeast-antifungal agent results for Mycototal and Mycostandard, 540 for Candifast, and 450 for ATB Fungus and Diff Test, repeatability was consistently equal to or greater than 95%. Reproducibility was 80.07% for Candifast and greater than 95% for the other systems. The concordance with the reference MICs was 51.65% for Candifast, 75.33% for ATB Fungus, 80.89% for Diff Test, 90.16% for Mycostandard and 90.32% for Mycototal. Although the performance of Diff Test and ATB Fungus was satisfactory, Mycototal and Mycostandard gave notably better results with imidazoles. Mycostandard, which is easier to use and includes tests for fluconazole and itraconazole, would seem to be potentially the most useful antifungal susceptibility test available at present. PMID- 8354300 TI - Detection of antibodies to Candida albicans germ tube as a possible aid in diagnosing systemic candidiasis in bone marrow transplant patients. AB - Indirect immunofluorescence assays to detect antibodies to Candida albicans blastospore and germ tube were performed in sera of 29 bone marrow transplant patients. Antibodies to germ tube were present in the sera of six patients, in four of whom a Candida albicans infection was highly probable, while in the other two patients it was not possible to determine the previous course. No healthy blood donors had these antibodies. On the other hand, detection of antibodies to Candida albicans blastospore showed low specificity in the diagnosis of systemic candidiasis. These preliminary findings suggest that the detection of antibodies to Candida albicans germ tube may be an important aid in the diagnosis of systemic candidiasis in bone marrow transplant patients. PMID- 8354301 TI - Ten-year survey of quinolone resistance in Escherichia coli causing urinary tract infections. AB - In a ten-year survey (1983-1992) of quinolone resistance in Escherichia coli causing urinary tract infections in a general practice patient population, 9,934 strains were tested. Resistance increased remarkably from 1989 onwards. The rate of resistance to pipemidic acid was < or = 6% before 1989 and 18% in 1992; the rate of resistance to ciprofloxacin (MIC > or = 4 mg/l) was 0.8% in 1989 and 7.1% in 1992. Although the consumption of older quinolones decreased the total consumption of quinolones increased yearly. PMID- 8354302 TI - Interpretive criteria and quality control parameters for determining bacterial susceptibility to fosfomycin tromethamine. AB - Studies with fosfomycin tromethamine disks containing 200 micrograms of fosfomycin and 50 micrograms of glucose-6-phosphate confirmed the following zone diameter criteria for the NCCLS method: < or = 12 mm for resistant (MIC > or = 256 micrograms/ml), 13-15 mm for intermediate (MIC 128 micrograms/ml) and > or = 16 mm for susceptible (MIC < or = 64 micrograms/ml). Additional studies defined acceptable MIC and zone diameter ranges for the following quality control strains: Escherichia coli ATCC 25922, MIC 0.5 to 4.0 micrograms/ml, zone diameter 23 to 29 mm; Staphylococcus aureus ATCC 25923, zone diameter 26 to 32 mm; Pseudomonas aeruginosa ATCC 27813, MIC 2.0 to 8.0 micrograms/ml; and Enterococcus faecalis, ATCC 29212, MIC 16 to 64 micrograms/ml. PMID- 8354303 TI - Comparison of fixed concentration and fixed ratio options for dilution susceptibility testing of gram-negative bacilli to ampicillin and ampicillin/sulbactam. AB - Ampicillin combined with sulbactam was tested at both fixed ratio (2:1 and 1:1) and fixed sulbactam concentrations (4 micrograms/ml, 8 micrograms/ml and 16 micrograms/ml) against 2440 consecutively isolated gram-negative bacilli. Sulbactam significantly enhanced the spectrum of ampicillin activity. Overall, at 8 micrograms/ml ampicillin inhibited 50% of the Enterobacteriaceae isolates, whereas 69% to 84% of the isolates were inhibited by the various sulbactam combinations. The widest spectrum of activity for ampicillin/sulbactam was achieved by testing at a fixed sulbactam concentration of 16 micrograms/ml, followed by the 1:1 ratio and the fixed 8 micrograms/ml (84%, 76% and 74% inhibited, respectively). The amount of sulbactam at the susceptible breakpoint concentrations of ampicillin markedly affected the percentage of susceptible strains. Combinations that include 8 micrograms/ml of sulbactam are suggested for consideration. PMID- 8354304 TI - Frequency and antimicrobial susceptibility of clinical isolates of enterococci. AB - A study was performed to determine the frequency and antimicrobial susceptibility of Enterococcus species in clinical specimens. Of 943 aesculin-positive isolates, 873 (92%) were identified as enterococci (737 Enterococcus faecalis, 129 Enterococcus faecium and 7 other Enterococcus species). High-level resistance to gentamicin was found in 15.2% of Enterococcus faecalis, but not in Enterococcus faecium; 58% of Enterococcus faecium were resistant to gentamicin at a concentration of 64 mg/l. None of the isolates were shown to possess vancomycin resistance. PMID- 8354305 TI - Detection of Helicobacter pylori in gastric biopsy tissue by polymerase chain reaction. AB - To evaluate the sensitivity of a polymerase chain reaction (PCR) assay using nested primers in detecting Helicobacter pylori, gastric tissue biopsy specimens were collected on endoscopy from 17 patients with a duodenal ulcer. DNA was extracted by phenol/chloroform treatment or boiling in water, and then subjected to a nested PCR using two primer pairs from the urease gene of Helicobacter pylori. Fourteen of the 17 patients were positive for Helicobacter pylori using DNA samples extracted by either method. The PCR results correlated well with the results of an enzyme immunoassay to detect IgG antibody. However, there were two culture negative patients. The three PCR negative patients were both culture negative and serologically negative. DNA from 9 of the 14 patients was randomly selected and subjected to semiquantification by serial dilutions, and then PCR. The results showed that phenol/chloroform extraction yielded 10-1000 times more DNA than the boiling method. It is concluded that the PCR assay is a rapid and sensitive method for detecting Helicobacter pylori, and that phenol/chloroform extraction is superior to simple boiling in obtaining DNA samples for PCR. PMID- 8354306 TI - Comparative in vitro activity of biapenem, a new carbapenem antibiotic. AB - Biapenem is a new carbapenem antibiotic with high stability to human renal dehydropeptidase I. Its in vitro activity was compared with that of imipenem, meropenem, ceftazidime, ceftriaxone, piperacillin and gentamicin against a total of 650 recent clinical isolates. MICs were determined by a standard agar dilution procedure and all isolates were tested at two inocula (10(4) and 10(6) cfu). Biapenem inhibited 90% of isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia stuartii, Enterobacter spp., Citrobacter freundii, Serratia marcescens, Salmonella typhi, Shigella sonnei and Yersinia enterocolitica at < or = 2 mg/l and was as active as or two- to four-fold more active than imipenem against all these species, with the exception of Serratia marcescens, against which imipenem was two-fold more active. Biapenem was two-fold more active than imipenem against Pseudomonas aeruginosa (MIC90 4 mg/l) and had activity similar to that of imipenem against the Bacteroides fragilis group (MIC90 0.5 mg/l) but was two-fold less active than imipenem against methicillin-susceptible Staphylococcus aureus (MIC90 0.06 mg/l) and was, like imipenem, inactive against methicillin-resistant Staphylococcus aureus. PMID- 8354308 TI - Epidemiology of invasive aspergillosis in European cancer centres. EORTC Invasive Fungal Infections Cooperative Group. PMID- 8354307 TI - Antimicrobial activity of the new carbapenem biapenem compared to imipenem, meropenem and other broad-spectrum beta-lactam drugs. AB - The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of the Enterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs against Pseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (including Bacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated for Xanthomonas maltophilia, oxacillin-resistant Staphylococcus spp. and Enterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad spectrum antibacterial agent for clinical use. PMID- 8354309 TI - Testing susceptibility of fungi to fluconazole. PMID- 8354310 TI - Screening for Chlamydia trachomatis and Neisseria gonorrhoeae in pregnant Turkish women. PMID- 8354311 TI - Determination of a new cut-off value for the diagnosis of congenital toxoplasmosis by detection of specific IgM in an enzyme immunoassay. PMID- 8354312 TI - Twenty-four hour blood pressure monitoring in healthy children. AB - Blood pressure and heart rate were measured every 20 min during the day and every 30 min during the night in 105 children (51 girls and 54 boys, aged 6-10 years) with a portable automated blood pressure monitor using an oscillometric principle of measurement. The monitor was well accepted by most of the children and the rate of invalid measurements was only 13%. Mean systolic and diastolic blood pressure was 114 +/- 7/72 +/- 5 by day and 99 +/- 7/56 +/- 6 by night. The corresponding heart rates were 93 +/- 8 and 72 +/- 9 beats/min. No significant differences were found between boys and girls. At night, systolic blood pressure dropped by 13% +/- 4%, the diastolic value by 22% +/- 7% and heart rate fell by 22% +/- 6%. Mean systolic and diastolic blood pressure measurements correlated positively with the subject's height, whereas no correlation was found with age. PMID- 8354313 TI - Physiological pulmonary branch stenosis in newborns: 2D-echocardiographic and Doppler characteristics and follow up. AB - Transient systolic murmurs in neonates and premature infants due to mild left (LPA) and right (RPA) pulmonary branch stenosis is recognized but follow up studies are lacking. We studied echocardiographically 21 neonates with murmur and 10 controls. Diameters of the main pulmonary artery (MPA), LPA and RPA were smaller in patients with murmur. Colour-coded Doppler showed turbulent flow in LPA and RPA in 20/21 (95%) patients and flow velocities of both pulmonary branches were significantly higher than in controls. The follow up study at 3 months in 14/21 (67%) patients showed absent or decreased murmur in 9 (64%). Echographically, absolute and relative diameters of LPA and RPA increased whereas the ratio of MPA/aorta did not change suggesting accelerated growth or dilatation of the pulmonary branches. Flow velocities decreased significantly in the branches. Thus, transient systolic murmurs in neonates are associated with temporary relative hypoplasia of the pulmonary branches which showed increased growth leading to disappearance of the murmur in most cases within 3 months of life. PMID- 8354314 TI - Apolipoprotein E phenotypes and plasma lipids in diabetic children and adolescents. AB - Apolipoprotein E (apoE) polymorphism is a genetic determinant of serum lipoprotein levels and coronary heart disease risk. ApoE appears in three major isoforms E2, E3 and E4, coded by corresponding alleles epsilon 2, epsilon 3 and epsilon 4. These give six different phenotypes. Patients with insulin dependent diabetes (IDDM) have been reported to have increased incidence of E2/2 homozygosity. We studied the frequencies of apoE phenotypes and their association with plasma lipids in 201 diabetic children, aged 2-17 years, and in 216 healthy controls with the same age range. Phenotyping was performed directly from plasma by iso-electric focusing and immunoblotting. Plasma total and high density lipoprotein (HDL) cholesterol (C) and triglycerides were determined by routine laboratory methods. Apolipoprotein A1 (apoA1) and B (apoB) were measured by turbidometry. There were no differences in apoE phenotype or allele distributions between the diabetic and control subjects. The frequencies of epsilon 2, epsilon 3, and epsilon 4 in the diabetic and control children were 0.08 versus 0.07, 0.73 versus 0.72 and 0.19 versus 0.21. The difference in apoE2/2 frequencies (2.0 in diabetic and 0.5% in normal children) was not statistically significant. In the diabetic children, there was a distinct relation between apoE phenotype and plasma lipids; presence of apoE2 was associated with the lowest and that of apoE4 with the highest concentrations of total and low density lipoprotein (LDL) C, and apoB. Ratios of HDL-C/LDL-C and apoA1/apoB showed on opposite trend. The influence of apoE polymorphism on plasma lipids was less clear in the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354316 TI - Silent carrier beta-thalassaemia due to a severe beta-globin mutation interacting with other genetic elements. AB - Beta-thalassaemia is caused by the presence of two mutated beta-globin genes, one inherited from each parent. We describe two families in which the diagnosis of beta-thalassaemia intermedia was delayed because one of the parents, an obligatory heterozygote, had normal haematological parameters (silent carrier beta-thalassaemia). DNA analysis revealed that these silent carriers were heterozygous for a point mutation in the polyadenylation signal (AATAAA-AATAAG). This defect is known to cause a moderately severe beta-thalassaemia phenotype. In one case, concurrent deletional alpha-thalassaemia was found in the silent carrier, which may have contributed to the mild phenotype. The increasing availability of DNA analysis should allow prompt diagnosis of such cases. Silent carrier beta-thalassaemia presents a diagnostic challenge to the clinician who evaluates children with anaemia. PMID- 8354315 TI - Interleukin-3, interleukin-6, granulocyte-macrophage colony-stimulating factor and erythropoietin cord blood levels of preterm and term neonates. AB - The cascade of known haematopoietic growth factors controlling granulomonopoiesis and erythropoiesis includes interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO). Elevated endogenous IL-3 and IL-6 cord blood levels in infection-free premature and mature neonates may reflect their possible role for expansion of haematopoietic progenitor cells, granulocytes and monocytes. Within the erythroid lineage a synergistic action of IL-3, IL-6 and EPO can be assumed. To identify the regulatory role in fetal haematopoietic expansion cord blood plasma levels of these haematopoietic growth factors were assessed in 19 premature and 20 mature infants using commercial enzyme-linked immunosorbent assay and enzyme-amplified sensitivity immuno assay test kits. Peripheral blood IL-3, GM-CSF and EPO were studied in 5 and 10 premature infants respectively. Compared with cord blood levels we found a decline in EPO levels but no decrease of IL-3 and GM-CSF during the 1st month of life. We conclude that postnatal decrease in plasma burst promoting activity levels in preterm infants is mainly explained by low postnatal EPO levels. PMID- 8354317 TI - Acute osteomyelitis and septic arthritis in the neonate, risk factors and outcome. AB - Twenty-two neonates with acute osteomyelitis (AO) or septic arthritis (SA) were included in a study based on a review of medical reports and a long-term clinical and radiological follow up. Clinical symptoms, bacteriology, risk factors, and outcome are discussed. The diagnoses were difficult, the clinical symptoms vague, fever rare and white cell count normal. Detection by plain radiological films was more efficient than by radionuclide bone scan. Staphylococcus aureus was the predominant causative organism and a shift towards group B Streptococcus in recent years was not identified. Risk factors for AO and SA were prematurity (13/22), respiratory distress syndrome (15/22) and perhaps most important: umbilical artery catheterisation (15/22). Severe sequelae were found in only 1 patient, while 3 patients had slight asymptomatic changes. The relatively favourable long-term outcome is unexplained, but may be related to early and appropriate, long lasting antibiotic treatment. PMID- 8354318 TI - Low level virus replication in infants with vertically transmitted fulminant hepatitis and their anti-HBe positive mothers. AB - Perinatal transmission of hepatitis B virus (HBV) occurs in about 10%-20% of anti HBe seropositive mothers. The babies are at risk of developing fulminant hepatitis. In most cases no viral DNA has been detected in the sera of mothers and children by conventional hybridisation techniques. Thus, the aim of our investigation was to demonstrate HBV DNA in three children with liver failure and their anti-HBe positive mothers by more sensitive molecular hybridisation techniques. The babies were healthy at birth and did not receive vaccination. At 3 months of age they developed acute liver failure and died from liver insufficiency. Only in one child serum HBV DNA was detected by dot blot hybridisation, but polymerase chain reaction (PCR)-detectable HBV DNA was present in all sera. The liver specimen was negative for HBV DNA by Southern blot hybridisation, but showed a focal distribution of viral sequences as determined by in situ hybridisation. This finding was confirmed by PCR. Our results prove that chronic anti-HBe positive HBsAg carrier mothers and their babies show a low level virus replication. Fulminant hepatitis is due to vertical transmission of very small amounts of viral DNA, only detectable by most sensitive techniques like PCR and in situ hybridisation. Our findings underline the necessity to vaccinate all babies of HBsAg positive mothers regardless of HBeAg/anti-HBe status. PMID- 8354319 TI - Oral cornstarch therapy: is persorption harmless? AB - Sediments prepared from freshly voided urine of four patients with glycogenosis Ia, or leucine-sensitive hypoglycaemia, on oral cornstarch therapy contained starch granules, evidence for persorption i.e. the incorporation of undissolved starch particles. In these patients, amyluria was more marked than in untreated controls. While cornstarch therapy is successful and causes few side-effects, the possibility of late adverse reactions to persorbed starch should not be disregarded. PMID- 8354320 TI - Continuous negative extrathoracic pressure and cardiac output--a pilot study. AB - Continuous negative extrathoracic pressure (CNEP) has been recently reintroduced as therapy for respiratory failure. To determine its effects on cardiac output a pilot study was performed in ten patients aged 2 months-3 years (median 4 months). All had chronic respiratory failure (seven with bronchopulmonary dysplasia). Five were breathing spontaneously and five were intubated and undergoing intermittent positive pressure ventilation. Transcutaneous oxygen saturation and PCO2, together with ECG were continuously monitored. Pulmonary artery blood flow velocity was measured non-invasively using pulsed wave Doppler. The 95% confidence intervals for the changes with and without CNEP in spontaneously breathing and ventilated patients showed no statistically significant changes in heart rate, O2 saturation, transcutaneous PCO2 or cardiac output. This study shows that the use of CNEP, administered in a tank respirator, does not lead to large changes in cardiac output. PMID- 8354321 TI - Ureaplasma urealyticum infection in newborns: three case reports. AB - We report three newborns with different manifestations of Ureaplasma urealyticum infection; a term newborn with acute neonatal pneumonia and two very low birth weight infants with bronchopulmonary dysplasia and osteomyelitis of the femur, respectively. The association of U. urealyticum with acute and chronic respiratory disease in term and preterm newborns has recently been reported. Our two cases are similar to other case reports from the literature, but we were unable to find any previous reports of osteomyelitis due to U. urealyticum in the premature babies. Isolation of U. urealyticum in pure culture from the blood was considered to be related to local infection in all three patients. All patients were cured by erythromycin. PMID- 8354322 TI - Efficacy of phototherapy in neonatal hyperbilirubinaemia associated with glucose 6-phosphate dehydrogenase deficient status. AB - The efficacy of phototherapy in a group of 427 infants with hyperbilirubinaemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency and a comparable group of 3924 G6PD normal infants with non-haemolytic hyperbilirubinaemia was evaluated. Phototherapy was highly effective in reducing bilirubin levels in both groups of infants, being significantly more effective in the group with normal G6PD status. Failure rate was very low (2.03/1000) in the group with normal G6PD status and nil in the G6PD deficient group. Bilirubin rebound after phototherapy was unremarkable with very few infants requiring a second exposure--4.68/1000 in the G6PD deficient group and 6.37/1000 in the G6PD normal group. All the babies tolerated phototherapy well. Phototherapy would therefore seem to be a simple and effective method for the management of severe jaundice associated with G6PD deficiency. PMID- 8354323 TI - Carbamazepine-induced skin rash in children with epilepsy. AB - The clinical and epidemiological findings in children with epilepsy who experienced skin rashes induced by carbamazepine (CBZ) were prospectively evaluated. Thirty-three (9.9%) of 335 patients who received CBZ therapy experienced a skin rash. Seven had diffuse erythema, 13 miliary exanthema, 11 maculopapular or speckled reddish rash, 3 petechiae, and 2 mucocutaneous syndrome. A skin rash was more frequent in older children (over 6 years old). The skin rashes appeared soon after initiation of the therapy, i.e., from the 8th to 60th day (mean: 14.3 +/- 9.6 days) after the start of CBZ therapy and disappeared within a few days after discontinuation of the therapy. Haematological abnormalities (30.3%), such as leucocytopenia and thrombocytopenia, and hepatic dysfunction (27.3%) sometimes appeared concomitantly with the skin rash. CBZ is an effective and safe antiepileptic drug, but careful management is necessary on initiation of the therapy. PMID- 8354324 TI - Guillain-Barre syndrome following immunisation with Haemophilus influenzae type b conjugate vaccine. AB - The Guillain-Barre syndrome (GBS) is an immune-mediated disease often associated with viral or bacterial infections and with immunisation. IgM antibodies have been implicated as the main trigger event in GBS. So far, only four cases of GBS have been observed following immunisation with a conjugate vaccine against Haemophilus influenzae type b. We report another patient with GBS after this vaccination. We measured immunoglobulins against the H. influenzae type b polysaccharide (PRP) component of the vaccine. Surprisingly the anti-PRP IgM antibody level was markedly elevated (100 micrograms/ml) in the plasma of this patient. We speculate that an excessive anti-PRP IgM antibody response to the vaccine might be the cause of GBS. PMID- 8354326 TI - Hepatorenal failure after carbamazepine therapy. PMID- 8354325 TI - The effect of sodium cromoglycate on upper and lower respiratory symptoms in children born prematurely. AB - The aims of this study were to assess whether sodium cromoglycate (SCG) was an effective prophylaxis against both upper and lower respiratory tract signs and to determine factors which affected the site and magnitude of the response to SCG. Sixteen children born prematurely were entered into a randomised placebo controlled trial at 15 months of age (range 4-31 months). The patients received, in random order, either 3 weeks' treatment with SCG (5 mg) or placebo, both given four times a day by inhalation via a spacer device. Parents were asked to record the occurrence and severity of their child's upper respiratory tract signs; sneezing and runny nose and lower respiratory tract signs; day and night time cough and wheeze. During the active compared to the placebo period there was an overall reduction of 47% and 53% in upper and lower respiratory tract signs, respectively. The magnitude of response to SCG as assessed by either the change in upper or lower respiratory tract signs was not significantly related to the patient's gestational or postnatal age, the occurrence of neonatal chronic lung disease, family history of atopy or the order in which the therapy was administered. We conclude that inhaled SCG may be a useful prophylaxis for both upper and lower respiratory tract signs for children born prematurely and less than 3 years of age. PMID- 8354327 TI - Discrete membranous subaortic stenosis in siblings. PMID- 8354328 TI - Ventilatory requirements for respiratory distress syndrome in small for gestational age infants. PMID- 8354329 TI - Complications of parenteral nutrition via an umbilical vein catheter. PMID- 8354330 TI - How to remove ingested batteries? PMID- 8354331 TI - Mechanisms of tubulo-interstitial injury in progressive renal diseases. AB - A vast amount of evidence, based upon human renal biopsy material, indicates that the presence of tubular atrophy and interstitial fibrosis is a better indicator of outcome of renal function than is the extent of glomerular sclerosis. The pathophysiological basis for this surprising fact has not been adequately addressed. In this review we point out that the systemic hypertension which accompanies most forms of chronic renal disease could impact adversely upon the vasodilated interstitial vascular compartment which, together with a component of primary capillary injury related to the disease process, could cause progressive obliteration of particular capillaries. This would initiate a process of chronic tubular ischaemia ultimately leading to tubular atrophy. Since tubular cells have been shown to produce an array of cytokines and growth factors which modulate fibroblast proliferation, extracellular matrix production and chemo-attracts for infiltrating cells, it is further proposed that it is the tubular injury which initiates the deleterious cascade of events. Tubular injury may be aggravated by the filtration of potentially 'noxious' molecules through the diseased glomerulus and by infiltrating cells. As the vascular bed into which glomerular blood flow empties is progressively obliterated, glomerular function declines and renal failure advances in relation to the degree of tubulo-interstitial fibrosis. PMID- 8354332 TI - Glucose-induced water movement from the intracellular to the extracellular space and its influence on calculations of glucose metabolism. AB - The osmotic effect of intravenous glucose was investigated in eight healthy volunteers. Increases in plasma glucose can induce water movement from the intracellular to the extracellular space. Serum choline esterase was used as an endogenous marker of serum dilution. Intravenous tests with 5, 15, 30 and 35 g of glucose showed that the water shift was proportional to the amount infused. The respective dilutions of choline esterase were 1.3 +/- 0.7%, 3.3 +/- 0.9%, 6.3 +/- 0.8% and 7.8 +/- 0.5%. The effect on extracellular water was maintained when plasma glucose remained elevated (inhibition of insulin secretion with a somatostatin analogue). In comparison to glucose, infusion of 10 g of a mixture of amino acids produced a less pronounced effect than expected. The acute water shift after intravenous glucose dilutes serum components including glucose (8% of total extracellular glucose at 35 g). This can be misinterpreted as glucose clearance when calculating metabolic rates. For estimated amounts a proportional correction should be made (3.5% per 5 mmol l-1 increase). A measured plasma glucose of 22.2 mmol l-1 should be corrected to 24.8 mmol l-1, while a plasma glucose value of 5.0 mmol l-1 needs no correction. PMID- 8354333 TI - Investigations into the haemorheological significance of postprandial and fasting hypertriglyceridaemia. AB - Two study designs were conceived to evaluate the rheological significance of hypertriglyceridaemia. We first investigated the course of serum- (SV) and plasma viscosity (PV) and erythrocyte aggregation in serum (SEA) and plasma (PEA) of healthy normolipidaemic individuals over 4 h after a fatty rich meal, in native material and after removal of triglyceride rich lipoproteins by centrifugation. Secondly, blood from patients with untreated hypertriglyceridaemia was investigated under fasting conditions. PEA and SEA increased in parallel with postprandial triglycerides (+135 mg dl-1), but the effect on PEA was more pronounced (+0.8 abs% increase; 2 h after the meal) as compared to SEA (+0.4 abs% increase). PV and SV increased in parallel to the same extent (+0.05 mPas). In the triglyceride poor infranatant no significant changes occurred. In fasting plasma PEA and PV were significantly lower (1.1 abs% and PV 0.04 mPas respectively) in infranatant than in native plasma, while only small differences in triglyceride (mostly VLDL) were observed. This phenomenon was barely detectable in serum samples. We conclude that triglyceride rich lipoproteins have a profound influence on haemorheological parameters, and that fibrinogen in particular, potentiates the effect of large fasting VLDL on plasma viscosity and erythrocyte aggregation. PMID- 8354334 TI - Bile concentration promotes nucleation of cholesterol monohydrate crystals by increasing the cholesterol concentration in the vesicles. AB - Cholesterol in bile is solubilized in mixed micelles and cholesterol-phospholipid vesicles. Biliary cholesterol supersaturation and increased concentration of bile in the gallbladder promotes nucleation of cholesterol monohydrate crystals and gallstone formation, possibly by creating unstable vesicles with a high cholesterol/phospholipid ratio. In the present study super-saturated and unsaturated biles (cholesterol saturation index (CSI) 1.4 and 0.8 respectively) were prepared with concentrations typical of gallbladder and more dilute hepatic bile (total lipid concentration (TLCo) 10 and 2.5 g dl-1 respectively). The distribution of cholesterol between vesicles and micelles, and vesicular cholesterol/phospholipid ratio were studied using ultracentrifugation and gel permeation chromatography. The nucleation time of cholesterol crystals was determined in whole model bile, and in the vesicular and micellar peak fractions. Increased CSI and bile dilution led to an increased proportion of cholesterol solubilized in vesicles. The concentration of bile did not influence vesicular cholesterol/phospholipid ratio. The vesicular cholesterol/phospholipid ratio found in gel-permeation chromatography experiments was similar at high and low CSI, whereas the ratio was significantly higher in supersaturated than in unsaturated biles in ultracentrifugation studies. Nucleation of cholesterol crystals from whole model bile was more rapid at the higher bile concentration and higher cholesterol saturation. Nucleation time in whole model bile correlated significantly with nucleation time in the corresponding vesicular peak fraction obtained by gel-permeation chromatography (r = 0.58: P < 0.01) and with the cholesterol concentration in this vesicular peak (r = -0.77; P < 0.002) but not with vesicular peak cholesterol/phospholipid ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354335 TI - Decreased in vitro oxidizability of low-density lipoprotein in hypercholesterolaemic patients treated with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors. AB - We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simvastatin and pravastatin on the in vitro susceptibility of low density lipoprotein (LDL) to oxidation. Twenty-three hypercholesterolaemic patients (mean serum cholesterol 9.7 mmol l-1) were treated with increasing doses of either simvastatin or pravastatin for 18 weeks. No significant differences in effect on lipid levels between the two drugs were found. Treatment resulted in lowering of total cholesterol and LDL-cholesterol by maximally 30% and 34%, respectively. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl-ester after treatment. The LDL cholesterol/protein ratio decreased from 1.24 +/- 0.21 to 0.97 +/- 0.23 (n = 20). By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidation after drug treatment. Maximal rate of diene production was significantly decreased from 19.7 +/- 3.1 to 18.5 +/- 3.3 nmol min-1 mg-1 LDL; total diene production decreased significantly from 420.3 +/ 67.6 to 380.5 +/- 49.1 nmol mg-1 LDL; the lag time was unchanged throughout the study. These studies show that HMG-CoA reductase inhibitors reduce the oxidizability of LDL by altering its composition. PMID- 8354336 TI - Long-term treatment with octreotide in patients with the Zollinger-Ellison syndrome. AB - This study reports the effects of 4 and 5-year treatment with octreotide (200 micrograms sc bid) in the Zollinger-Ellison syndrome (ZES). No symptoms related to acid hypersecretion were observed in the four patients throughout the study, and upper GI endoscopy was normal. Basal acid output (BAO) measured 12 h after injection, was below 10 mmol h-1 in three to four patients and previous ranitidine treatment was discontinued. In the fourth case (pretreatment BAO value: 115 mmol h-1), BAO progressively decreased to 42 mmol h-1 after 5 years of octreotide treatment. At the end of the study, serum gastrin levels were 58.5% (30-68) of the pretreatment values and two patients had normal gastrin levels. Peak acid output (PAO) decreased markedly after 2, 4 and 5 years, by 68% (35-89) suggesting that octreotide had exerted an antitrophic effect on parietal cell mass. Diffuse hyperplasia of fundic argyrophil cells present in two patients before octreotide, decreased during the treatment. Mean argyrophil cell density for all patients was not significantly modified. Antral gastrin-cell density was in the normal range. No long-term side effect of octreotide treatment was observed. Although octreotide may not be considered as a substitute for benzimidazoles in the treatment of ZES, its specific properties may be of therapeutic benefit in some ZES patients. PMID- 8354337 TI - Postabsorptive retinyl palmitate removal is retarded in lecithin-cholesterol acyltransferase deficiency. AB - Postabsorption fat clearance of intestinal lipoproteins indicated by retinyl palmitate was studied in two siblings with the classical lecithin-cholesterol acyltransferase (LCAT) deficiency and in a control group of 21 healthy subjects with similar apoprotein E 3/3 phenotype. Relatively high pre- and postabsorptive cholesterol esterification percentage of chylomicrons suggested that acyl coenzyme A:cholesterol acyltransferase activity was not inhibited. Postabsorptive levels of plasma lipids increased and decreased roughly similarly in the cases and controls with the postabsorptive peak values at about 4 h. Plasma total and chylomicron levels of retinyl palmitate were not affected by LCAT deficiency, while the removal of the vitamin from very low and intermediate density lipoproteins was clearly reduced so that the peak concentrations, values under the response curves and the time of the peak concentrations were markedly higher than in the controls. The long-lasting circulation of chylomicron remnants of density < 1.006-1.019 g ml-1 may have some clinical significance because postabsorptive lipoproteins are suspected to have atherogenic potentiality. PMID- 8354338 TI - On the relationships between mineral metabolism, obesity and fat distribution. AB - Alterations in calcium metabolism have been associated with cardiovascular risk factors. An altered binding of calcium to plasma proteins and raised levels of parathyroid hormone (PTH) have been described in morbid obesity. In the present study, indices of mineral metabolism were related to obesity (body mass index, BMI) and fat distribution (waist to hip ratio, w/h) in 194 subjects with a wide range of BMI and w/h. The ratio of total serum calcium to plasma ionized calcium (Ca2+) was found to be significantly correlated to both BMI (r = 0.20, P < 0.02) and w/h (r = 0.22, P < 0.005). Serum phosphate was also correlated to both of the indices of obesity in an inverse way (r = -0.24, P < 0.0008 for BMI and r = 0.33, P < 0.0001 for w/h). These relationships were still significant when the influences of age, sex and serum creatinine were included in the multiple regression analysis. This kind of analysis also disclosed that w/h was superior to BMI as a determinant of serum phosphate and the total calcium/Ca2+ ratio in serum. PTH was not significantly correlated to any of the indices of obesity. In conclusion, fat distribution rather than obesity per se was found to be associated with an altered mineral metabolism. PMID- 8354339 TI - Pancreatic beta-cell function and interleukin-1 beta in plasma during the acute phase response in patients with major burn injuries. AB - Animal experiments demonstrate that interleukin-1 beta (IL-1 beta) is beta-cell cytotoxic in vitro and inhibits insulin secretion in vivo. However, it is unknown if IL-1 beta affects beta-cell function in man. Since IL-1 beta and other cytokines are main mediators of the acute phase response, the objectives of the present study were to examine beta-cell function in patients with major burn injuries, and to test if changes in beta-cell function correlated to systemic levels of IL-1 beta and tumour necrosis factor alpha (TNF alpha). We established and validated an IL-1 beta assay measuring free and protein bound IL-1 beta; protein bound IL-1 beta was detached from the IL-1 beta specific binding protein by acidification, rendering it accessible for the employed antibody. The IL-1 beta specific binding protein (43-60 kDa) was found in serum and plasma from all tested patients and normal subjects. Survivors of burn injuries had a stimulated beta-cell function, whereas non-survivors had an impaired beta-cell function as indicated by an increased plasma concentration of proinsulin, and an increased proinsulin/insulin ratio. In addition, non-survivors had significantly increased plasma levels of IL-1 beta. However, we could not demonstrate any correlation between C-peptide, proinsulin, insulin or proinsulin/insulin ratio and plasma concentration of IL-1 beta. In conclusion, beta-cell function abnormalities are evident in patients with major burn injuries, and a high plasma level of IL-1 beta correlates with a fatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354341 TI - The endothelin ETA receptor-specific effect of 50-235, a nonpeptide endothelin antagonist. AB - We characterized the endothelin receptor antagonist 27-O-caffeoyl myricerone (50 235), isolated from the bayberry Myrica cerifera, using rat aortic smooth muscle A7r5 cells that express ETA receptors and human Girardi heart cells that express ETB receptors. 50-235 concentration-dependently inhibited 125I-ET-1 binding to A7r5 cells with Ki of 51 +/- 12 nM, while it had no effect on 125I-ET-1 and 125I ET-3 bindings to Girardi heart cells. Also in affinity cross-linking studies with 125I-ET-1, 50-235 inhibited labeling of a protein of M(r) = 67,000 in A7r5 cells, but did not inhibit labeling of two proteins with M(r) values of 70,000 and 46,000 in Girardi heart cells. Functionally, 50-235 inhibited the ET-1-induced increase in cytosolic free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner (IC50 = 11 +/- 2 nM) in A7r5 cells. On the other hand, this compound had no effect on the basal level of [Ca2+]i and the high K(+)- and bombesin-induced increases in [Ca2+]i in A7r5 cells, nor on the ET-1-induced increase in [Ca2+]i in Girardi heart cells. Also, 50-235 inhibited ET-1-promoted mitogenesis of A7r5 cells. Thus, we conclude that 50-235 is a specific endothelin A receptor antagonist that could be very useful for elucidating the physiological and pathophysiological significance of ET. PMID- 8354340 TI - Binding of the muscarine receptor antagonist heptane-1,7-bis(dimethyl-3' phthalimidopropyl)ammonium bromide at cholinoceptor sites. AB - The binding of the bisquaternary muscarine receptor antagonist heptane-1,7 bis(dimethyl-3'-phthalimidopropyl)-ammonium bromide (C7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[3H]nicotine, [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate ([3H]QNB) in both central and peripheral tissues. C7/3-phth displayed an affinity for muscarine M2 receptors in rat atria (70.1 nM) which was 1.6-fold greater than for putative M4 receptors in rabbit lung, and 4- to 5-fold greater than for M1 receptors in rat cerebral cortex. Its affinity for nicotine receptors in the cortex was low, being 808-fold lower than its affinity for the M2 receptor. Although the displacement of (-)-[3H]nicotine and [3H]pirenzepine binding in rat cortex by C7/3-phth was best described in terms of one-site modelling, low Hill coefficients were observed with C7/3-phth in displacement studies using [3H]QNB in this tissue. The possibility of allosteric interactions or multiple receptor subtype interactions is discussed. PMID- 8354342 TI - Polyclonal anti-idazoxan antibodies: characterization and purification. AB - Amino-idazoxan coupled to hemocyanine was used to raise anti-idazoxan antibodies in the rabbit. The antibodies were affinity purified with an amino-idazoxan affinity column. Binding studies with [3H]idazoxan showed a dissociation constant of 2.2 +/- 1.4 nM. The specificity spectrum of these antibodies indicates that the imidazoline part of idazoxan is more important for recognition than the benzodioxan ring as imidazoline substances (clonidine, cirazoline) are powerful competitors of [3H]idazoxan binding on the antibodies. Catecholamines or imidazoles were unable to displace [3H]idazoxan from the antibodies. These anti idazoxan antibodies present specificity similarities with the imidazoline receptor as did our previously obtained anti-clonidine antibodies. Affinity purified antibodies represent useful tools for studying the imidazoline receptors particularly with an anti-idiotypic approach. PMID- 8354343 TI - Metformin and brown adipose tissue thermogenetic activity in genetically obese Zucker rats. AB - The effect of chronic metformin treatment on brown adipose tissue thermogenetic activity was investigated in young genetically obese Zucker rats. The binding of [3H]GDP to brown adipose tissue mitochondria, expression of uncoupling protein mRNA in brown adipose tissue, weight gains and cumulative food intakes were measured in metformin (320 mg/kg orally for 12 days)-treated obese Zucker rats as well as in pair-fed--and in ad libitum--fed control obese rats. The weight gains were identically reduced in the metformin- and pair-fed control group compared to the ad libitum--fed rats. Metformin also significantly reduced cumulative food intake. The binding of [3H]GDP to brown adipose tissue mitochondria and the expression of uncoupling protein mRNA in brown adipose tissue were not modified by metformin. It is concluded that the weight gain reducing effect of metformin in obese Zucker rats is mainly due to reduced food intake and does not involve an effect of metformin on brown adipose tissue thermogenetic activity. PMID- 8354344 TI - Up-regulation of 5-HT2 receptors in the rat brain by repeated administration of SR 46349B, a selective 5-HT2 receptor antagonist. AB - Chronic administration (twice a day for three days and on the morning of the fourth day) of SR 46349B (trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3-(2 fluoroph enyl)propen-1- yl]phenol hemifumarate) (10 mg/kg, orally), a selective 5 HT2 receptor antagonist, caused 24 h later a marked increase (+42%) of the maximum binding capacity of [3H]ketanserin in rat brain cortical membranes without change in its affinity constant. Further, administration of the 5-HT2 receptor agonist, (+/-)-DOI((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (1 mg/kg, i.p.), produced in chronic SR 46349B treated rats a significant increase in the amount of [3H]-inositol phosphate compared to corresponding controls. In addition, subacute administration of SR 46349B caused a 2-fold increase in the head-twitch response to (+/-)-DOI (0.5 mg/kg, i.p.). This enhanced response was blocked by an acute administration of ritanserin (6-(2-[4 [bis(4-fluorophenyl)methylene]-1-piperidinyl]ethyl]-7- methyl-5H-thiazolo[3,2 a]pyrimidin-5-one) (10 mg/kg). Finally, a significant enhancement (+29%) of 5-HT2 receptor mRNA levels was observed in the cortex. Taken together, these data showed that an up-regulation of 5-HT2 receptors occurred in rats following repeated treatment with a selective 5-HT2 receptor antagonist. The effects of SR 46349B on 5-HT2 receptors might implicate pre-translational regulation. PMID- 8354345 TI - Evidence that protein kinase C alpha has reduced affinity towards 1,2-dioctanoyl sn-glycerol: the effects of lipid activators on phorbol ester binding and kinase activity. AB - The effect of 1,2-diacylglycerols on specific binding of [3H]phorbol 12,13 dibutyrate to cytosolic protein kinase C (PKC) was investigated in tissues reported to contain different proportions of PKC isoforms. In lung, frontal cerebral cortex and cerebellum cytosols (enriched in PKC alpha, beta and gamma, respectively) displacement of specific binding by phorbol 12,13-dibutyrate or diacylglycerols containing unsaturated acyl chains was of similar potency for each tissue. A range of 1,2-diacylglycerols containing saturated acyl chains exhibited varying affinities for [3H]phorbol 12,13-dibutyrate binding sites in each tissue; defining an optimal acyl chain length of around 14 carbons in each case. However, the affinities of saturated diglycerides were consistently lower in lung cytosol than in frontal cerebral cortex and cerebellum cytosols, with the greatest differences occurring at lower acyl chain lengths, especially with 1,2 dioctanoyl-sn-glycerol. Furthermore, a mixed micelle assay of PKC activity showed that 1,2-dioctanoyl-sn-glycerol displayed reduced potency at PKC alpha partially purified from COS 7 cell cytosol compared to the mixture of PKC isoforms present in rat midbrain cytosol. Both low potency of 1,2-dioctanoyl-sn-glycerol as a displacer of [3H]phorbol 12,13 dibutyrate binding and the ability of arachidonic acid to act as an allosteric enhancer of binding, correlated with the proportional PKC alpha content of a range of tissues reported in the literature. In PKC enzyme activity assays, 1,2-dioctanoyl-sn-glycerol, but not phorbol 12,13 dibutyrate, was correspondingly a much poorer activator of PKC alpha from COS 7 cells than of the broad consensus of isoforms in rat midbrain. When alpha and beta isoforms were extensively-purified on DEAE-cellulose then hydroxyapatite, both the low affinity of 1,2-dioctanoyl-sn-glycerol for [3H]phorbol 12,13 dibutyrate binding sites and their allosteric regulation by arachidonic acid were confirmed to be characteristic of the alpha rather than the beta isoforms. PMID- 8354346 TI - [Biological function models with wild-derived genes. Why do we have to use mice, in particular wild derived mice, for the biomedical research?]. PMID- 8354347 TI - [Gene therapy of a lethal mutation associated with adrenal hyperplasia in mice]. PMID- 8354348 TI - [Development of animal models for carcinogenesis by transgenesis. Transgenic mouse models for cancer research]. PMID- 8354349 TI - [Usefulness of transgenic mice in carcinogenicity tests]. PMID- 8354350 TI - [What mouse contributed the first representation of the adrenal cortex X zone?]. AB - The X zone, innermost cortex of the mouse adrenal, was first represented by Kiyoshi Masui and Yasushige Tamura in the Japanese in 1924 and in the English in 1926. All the mice used by them were reared by themselves at the Laboratory of Veterinary Anatomy, Faculty of Agriculture, Imperial University of Tokyo. They were the first scientists in Japan that attempted to breed mice in their own laboratory and used them for scientific researches in the literature. The importance of the breeding of laboratory animals by users was first pointed out by Sahachiro Hata in 1914, who found Salvarsan as a specific medicine against Spirochaeta pallida in cooperation with Paul Ehrlich in 1910. Hata's idea on the breeding of laboratory animals by researchers themselves might inspire Masui. Hata himself tried to breed laboratory mice in the Kitasato Institute. They were called "French mice", because they were believed at that time to be introduced from Europe before 1910. Masui and Seitaro Adachi (1926) also used French mice in their basic studies. They compared the body size between French and Nanking mice with special attention to the genetic factors controlling the body size for the purpose of improving of army horses. They noticed that French mice were larger in body size and more active in reproduction. Hata noticed a difference in reaction to Salvarsan between two mice. Our survey of the literature revealed that the X zone in the mice used by Masui and Tamura had many distinctive characteristics. The major two found in 90-day-old virgins were the extremely thick X zone and its division into two sublayers, one being composed of vacuolated cells only and the other of non-vacuolated cells only. It seems most reasonable to postulate that the first representation of the X zone was made in French mice bred by Masui and Tamura themselves. These characteristics of the X zone in the mice used by Hata or Masui and Tamura were very similar to those observed in inbred strains of mice, KK and NC, which Kyoji Kondo established from Japanese fancy mice, Kasukabe and Nishikinezumi groups, respectively. The same characteristics were also found in 4 of 28 recombinant inbred (RI) strains between A/J and SM/J established by Masahiko Nishimura. Since both A/J and SM/J have not such characteristics, the thick X zone consisting of 2 sublayers with and without vacuolation seems to appear on a certain specific genetic background.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8354351 TI - Cryopreservation of mouse spermatozoa from inbred and F1 hybrid strains. AB - Mouse epididymal spermatozoa from inbred(BALB/c, C3H/He, C57BL/6N, CBA/JN and DBA/2N) and F1 hybrid (B6C3F1, BDF1 and CDF1) strains suspended in cryopreservation solution (18% raffinose and 3% skim milk in distilled water) were frozen and stored at -196 degrees C. After thawing at room temperature, sperm motility and fertilizing ability were examined. Spermatozoa from all of the strains were successfully frozen, although the motility and the fertilization rates of frozen-thawed spermatozoa (the proportions of the fresh oocytes from Jcl:ICR strain which developed to pronuclear oocytes and 2-cell embryos after insemination by frozen-thawed spermatozoa) varied among strains (motility: 23% for C57BL/6N to 62% for DBA/2N; fertilization rates: 26% for C57BL/6N to 89% for DBA/2N). Nearly all 2-cell embryos fertilized by frozen-thawed spermatozoa were transferred to the oviducts of pseudopregnant recipients and 35-62% of 2-cell embryos developed into normal young. PMID- 8354352 TI - [Possibility of detecting visual functional disturbance in rats by the open-field test]. AB - In order to determine whether visual disturbance in small rodents is detectable by means of the open-field test, the ambulation scores of enucleated and intact rats in an open-field were measured. In a 30-min test of Slc:Wistar/ST rats, there were significant differences in ambulation scores between enucleated and intact rats in the first 10-min. In addition, the effects of observation times (09:00-11:00, 13:00-15:00 and 17:00-19:00 hr) and strains on the open-field test were studied using a 10-min test. Regardless of observation times, ambulation scores of enucleated rats of the Slc:Wistar/ST and F344/N Slc strains were significantly elevated as compared with those of intact rats from both strains. When tested during the 13:00-15:00 hr period, there were significant differences in the Slc:SD rats. These findings indicate that the changes in ambulation are due to visual disturbance. However, significant ambulatory changes in F344/N Slc rats were documented at the three different observation times. Based on these results, Slc:Wistar/ST rats appear to be suitable for detecting visual disturbance by the open-field test. PMID- 8354353 TI - [Morphometric studies on the effects of dehydration on the renin-immunopositive cells in the kidney of the Mongolian gerbil (Meriones unguiculatus)]. AB - Effects of dehydration on the total area of the kidney occupied by renin immunopositive cells were morphometrically studied on parasagittal sections by an image-analyzing system in the Mongolian gerbils. Changes in the body weight and plasma osmolarity were simultaneously measured to compare with morphometric data. The body weight decreased rapidly at the beginning, and gradually after 10 days of dehydration. On the other hand, the plasma osmolarity showed no significant change at 2 days, increased gradually after 5 days, and reached a plateau after 15 days. Similarly, the total area of renin-positive cells showed no significant changes at 2 days, increased remarkably after 5 days, and reached a plateau after 15 days. These findings suggest that the plasma osmolarity and total area of renin-positive cells showed no significant changes at the beginning of dehydration because the increase in the plasma osmolarity was compensated by the expenditure of inter-and intra-cellular fluid, and the total area of renin positive cells was increased in response to the acceleration of renin synthesis stimulated by the increase in the plasma osmolarity after a certain period of dehydration. The total area seemed to be maintained on a certain level because the further increase in the plasma osmolarity was suppressed by the excretion of electrolytes from the body in proportion to the water loss after a long period of dehydration. PMID- 8354354 TI - [Application of DNA fingerprinting to investigation of genetic relationships between laboratory rabbit strains]. AB - It is well known that laboratory rabbits are not controlled genetically like laboratory mice and rats. In order to test the usefulness of DNA fingerprinting in investigation of genetic uniformity of the laboratory rabbits strains and their relationships, we applied DNA fingerprinting using bacteriophage M13 probe to five strains (2 inbreds (JWY-NIBS and DuY-NIBS) and 3 outbreds (JW-NIBS, Icl:JW and WHHL)). DNA fingerprints of 2 inbred strains showed the same banding patterns within each strain but the strain-specific patterns. Although there were no rabbits showing the same banding patterns in 3 outbred strains, average percent differences (APD) were 13.7 to 18.6. A dendrogram based on APD of DNA fingerprints was constructed by 2 large clusters, JW group and DuY. The dendrogram was essentially similar to that based on rabbit mandible measurements. These results suggest that DNA fingerprinting is available not only for the genetic monitoring of the laboratory rabbit strains but also for the investigation of their genetic relationships. PMID- 8354355 TI - Establishment of inbred strain of long-haired golden hamster. AB - Features of a long-haired mutant and inheritance of mutation were investigated in the golden hamster (Mesocricetus auratus). The hair of adult long-haired hamsters was longest at the rump and flanks (approximately 70 mm) and was also unusually long at the neck (45 to 50mm). The hair length of males was more striking than that of females. Mating experiments indicated that an autosomal recessive gene is responsible for the inheritance of long hair. An albino long-haired hamster strain was established by continuous full-sib mating from F2 hybrids, descendants of (acromelanic albino x agouti long-haired) F1 progeny, and genetic homogeneity was confirmed by DNA fingerprinting. The long-haired strain was characterised by the fact that males grew larger than females, in contrast to the other strains of hamsters. PMID- 8354356 TI - [Age-related changes in bone weights and their components in rats]. AB - Age-related changes in the wet, dry and ash weights and components such as water, organic substance, ash, calcium and phosphorus of femur, tibia and first lumbar vertebra and serum biochemical constituents related to bone metabolism were examined in Wistar rats. A total of 60 males and 60 females were used, and every five rats of both sexes were examined at 1 and 2 months of age and then at intervals of 3 months between 3 and 30 months of age. Each bone weight increased rapidly up to 3 months of age and then gradually up to 12 months of age in females and 9 months of age in males, but thereafter decreased at 27 and 30 months of age in males. Between 1 and 6 or 9 months of age in both sexes, a decrease in water content, increases in ash, calcium and phosphorus, and almost no change in organic substance in each bone were observed. After 15 months of age in males, an increase in water content, decreases in ash content, calcium and phosphorus, and almost no changes in organic substance were observed in males. The value of serum calcium decreased up to 12 months of age but then increased after 18 months of age in both sexes. Serum phosphorus and alkaline phosphatase activity decreased up to 9 months of age in both sexes. The data obtained in this study supported the results in our previous study that the peak bone strength of the femur and peak bone volume of trabecular bone of the proximal metaphysis of the tibia were at 12 months of age in both sexes in Wistar rats. PMID- 8354357 TI - [Visual evoked potential from dura in rats]. AB - Visual evoked potentials (VEPs) were recorded from 8 different points (from points A and B near the bregma to points G and H near the occipital bone) of the dura under parietal bone in rats. The study was performed with 68 adult male Slc: Wistar/ST rats weighing 259.9-298.0g. VEPs recorded from the dura had a large negative component with a peak around 45 msec (N1), a large positive component with a peak around 75 msec and a large negative component with a peak around 120 msec (N2). Points A and B were not suitable for recording of the VEPs because some rats showed no N2 peak. The amplitude of peaks N1 to P at point E, upper the left optic layer of the superior colliculus, was higher than those from other points. Point E was the best position for recording of the VEP from dura in Slc: Wistar/ST rats. PMID- 8354358 TI - Characterization of mycoplasma strains isolated from house musk shrews (Suncus murinus) and their infectivity in mice and rats. AB - Five mycoplasma strains isolated from house musk shrews (Suncus murinus) in the Central Institute for Experimental Animals were characterized and compared with three murine mycoplasma strains, Mycoplasma pulmonis m 53, M. arthritidis PG6, and M. neurolyticum Type A, and with reference strain G3-5 previously isolated from a house musk shrew. These isolates fermented glucose, but did not hydrolyze urea and arginine, passed through membrane filters of 450 nm pore size, were sensitive to digitonin, and formed minute (115 to 231 microns in diameter) colonies on agar medium. All the five unclassified house musk shrew mycoplasma strains and strain G3-5 used as a reference constituted a homogeneous group based on (i) their antigenic properties (determined using the metabolism inhibition test), (ii) their polypeptide profiles (determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis and the Western blotting assay), and (iii) their genomic properties (determined using DNA cleavage pattern analysis), but were quite distinct from the established murine mycoplasmas on the basis of these findings. In a survey of 56 house musk shrews aged 2 to 45 weeks in our colonies, mycoplasmas were isolated from the oral cavities of all animals examined. No gross or microscopic lesions were observed in the five animals from which the mycoplasma strains were isolated. In experimental infection, the mycoplasma was not infective for mice and rats. The results suggest that this group of mycoplasmas is a common inhabitant of house musk shrews. PMID- 8354359 TI - Serological evidence of pneumonia virus of mouse (PVM) infection in laboratory rats. AB - PVM specific antibody was determined using 3 serological tests (Parker's original hemagglutination-inhibition [HI] test, modified HI test, and indirect fluorescent antibody [IFA] test). IFA test was found to be the most sensitive method, so that IFA test was considered to be the method of choice for a small scale microbiological monitoring in animal facilities. A total of 1,280 sera including rats, mice, hamsters and rabbits were tested for PVM antibody. The prevalence of PVM antibody was 17.2% (116/674) in conventional rats and 30.0% (160/200) in SPF rats obtained from commercial breeders and research facilities. Furthermore, two samples of 144 conventional rabbits (1.4%) were showed specific antibody positive to the virus. However, hamsters and mice showed no evidence of PVM infection. These results suggest that PVM infection is prevalent, especially in laboratory rats in Japan. PMID- 8354360 TI - Postnatal development of the auditory brainstem response (ABR) in beagles. AB - Postnatal development of the auditory brainstem response (ABR) in beagles was studied by repeated ABR recordings from birth to 16 weeks of age. In ABR recording, waves I, II and III appeared at the same time 13 to 17 days of age, while wave IV during 13 to 20 days of age and wave V during 20 to 35 days of age, respectively. The latencies of waves II, III and IV became close to the control level at 6 weeks of age, whereas wave I had a similar latency to the control at 3 weeks of age. The latency of wave V became close to the control level at 8 weeks of age. I-III interpeak latency stabilized at 4 weeks of age, however, I-V and III-V interpeak latencies stabilized during 8 to 10 weeks of age. There was a marked individual difference in amplitude of ABR components in beagles. Wave I amplitude reached the plateau level at 3 weeks of age, and wave II, III and IV at 6 weeks of age. No further development in ABR was observed on and after 10 weeks of age. It may be concluded, from electrophysiological point of view, that the peripheral auditory pathway matures at 3 weeks of age and the auditory rely system in brainstem at 10 weeks of age in beagles. PMID- 8354361 TI - Historical control data of organ weight and gross findings in F344/DuCrj rats and B6C3F1 mice. AB - Organ weight and gross postmortem findings of control Fischer 344/DuCrj rats and B6C3F1 mice are presented from subchronic, chronic toxicity and carcinogenicity studies that were conducted over a 9 year period at our center (An-Pyo Center). The mean organ weight of the liver, kidney, spleen and the lung were increased associated with age in both species. The most common findings observed at 109 weeks in both species were thymic atrophy, enlargement of the spleen, dilation of the lumen of the uterus and ovarian cysts. Male and female Fischer 344/DuCrj rats commonly exhibited a granular surface of the kidneys, hypertrophy of and/or nodular pituitary glands and subcutaneous tissue masses. Multiple white patches and hypertrophy or atrophy of the testes, atrophy of the seminal vesicles and prostate and nodules in the pancreas were seen frequently in male rats. Malformative nodule in the liver was a common finding in female rats. The most common lesions seen in both male and female B6C3F1 mice were nodules in the liver and lungs and enlargement of the lymph nodes. Nodules on the preputial gland were commonly seen in the males. Sex differences were evident in the incidence of some of the above findings. These historical data will contribute to analyze the organ weight and gross findings at necropsy in long-term toxicity and carcinogenicity studies. PMID- 8354362 TI - Mortality, body weight, food and water consumption, and clinical signs in Slc: B6C3F1 (C57BL/6 x C3H) mice utilized in chronic toxicity and carcinogenicity studies. AB - In vivo historical control data for Slc: B6C3F1 mice, including mortality, body weight, food and water consumption, and clinical signs and which were obtained from long-term toxicity and carcinogenicity studies (11 male and 12 female studies) conducted at the Biosafety Research Center, Foods, Drugs and Pesticides, (An-Pyo Center) during the last five years are presented. Mean survival at 83 and 109 weeks of age was 96.4% (min: 94.0%, max: 100%) and 79.0% (min: 74.0%, max: 86.0%) in males and 98.7% (min: 96.0%, max: 100%) and 81.7% (min: 70.0%, max: 90.0%) in females, respectively. The maximum mean body weight of males and females was 45.1 +/- 3.1 g (mean +/- S.D.) and 39.2 +/- 4.1 g, respectively. Male mice attained their maximum body weight at 72.7 +/- 4.3 weeks of age and females at 76.2 +/- 5.9 weeks of age. Clinical symptoms increased with age, particularly after week 84, and included: wasting, piloerection and palpable abdominal masses. Hypothermia and auricular pallor were common findings in moribund animals from week 79 to 104 of the studies. The use of in-house, historical control data can prove invaluable in the evaluation and interpretation of experimental results, especially in long-term and life-time studies. PMID- 8354363 TI - Comparison of electron irradiation diets and gamma irradiation diets for reproductive effects on rats. AB - Rats were maintained on 50 kGy electron irradiation diets. Effects of the diets on reproductive performance of parents and developmental performance of fetuses (F1 and F2) were studied by comparison with data in rats maintained on gamma irradiation diets, as control animals, and the background data of our facility. As the result, no specific changes were observed in the group maintained on electron irradiation diets. Electron irradiation diets sterilized under the condition of 50 kGy irradiation in the present study, as well as the existing gamma irradiation diets, were found to be useful for breeding and nursing rats. PMID- 8354364 TI - [Fine structure of the vomeronasal organ in the house musk shrew (Suncus murinus)]. AB - Fine structure of the vomeronasal organ (VNO) was examined in an insectivore, house musk shrew (Suncus murinus), from a viewpoint of comparative anatomy. The VNO was a pair of tubular structure, about 6mm in length, and situated at the base of the nasal septum. The medial wall of the lumen of the VNO was lined with the sensory epithelium (SE) consisting of sensory, supporting and basal cells, while the respiratory epithelium (RE) lining the lateral wall was pseudostratified and covered with microvilli. Jacobson's glands were distributed on the dorsolateral to ventrolateral side of the VNO and opened to the lumen in the transitional region from the RE to the SE. Their secretion was PAS-positive bu talcian blue-negative. Ultrastructurally, sensory cells of the SE were bipolar neurons and covered on their free surface with conspicuously long microvilli. The other ultrastructural features in sensory, supporting and basal cells were similar to those in previously reported species. The ultrastructural features of the RE were also similar to those in previous reports except that the free surface was covered with microvilli instead of cilia. In addition, a few kinds of migrating cells were often observed in both the SE and the RE. Acinar cells of Jacobson's glands possessed a round to elliptical nucleus and many large secretory granules, about 1,000 nm in diameter. Rough endoplasmic reticulum and Golgi apparatus were well developed in their cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354365 TI - [Learning dysfunction model in ddY mouse and IgG]. AB - Mice of the ddy strain having once received an electric shock in the dark chamber of a passive avoidance response unit were divided into two groups according to their behavior pattern. It is suggested that learning function of the mice which did not avoid the dark chamber (negative-avoidance mice: N-mice) was disturbed. After an injection of IgG obtained from the positive-avoidance mice (P-mice) into the N-mice, these prior N-mice displayed the behavior pattern similar to that of P-mice following an application of electric shock. It was found that the sugar chain structure of N-mouse IgG was different from that of P-mouse IgG. This result indicates that the sugar chain structure is related to the learning ability of ddy mice. PMID- 8354366 TI - [Lectin histochemical studies on the musk gland in the house musk shrew (Suncus murinus)]. AB - The musk gland of the adult house musk shrews (Suncus murinus) of both sexes was studied lectin histochemically. The musk gland was a kind of scent gland, consisted of congregation of branched or unbranched simple tubuloalveolar gland holocrine in nature and was attached by an apocrine gland-like structure (sweat gland) in the deeper layer of its periphery. Acinar cells of the musk gland were distinguishable into three type from basal to luminal parts of the acinus; immature cells, mature cells and degenerating cells. There was no histological difference between both sexes. Lectin-binding pattern of the musk gland was examined in comparison with that of the sweat gland and ordinary sebaceous gland by histochemical staining techniques using seven lectins: ConA, RCA I, PNA, SBA, UEA-I, DBA, WGA, WGA and PNA labelled the duct of the musk gland more intense than the acinus. Several lectins showed a tendency to label the cells situated near the luminal surface more intense than those near the basement membrane in both the acinus and duct of the musk gland. In the sweat gland and ordinary sebaceous gland, the lectin-binding pattern was different with each other and from that in the musk gland. These findings suggest that the musk gland, sweat gland, and ordinary sebaceous gland are different to each other in nature of cells and the secretion. PMID- 8354367 TI - [Relative growth of physiques in laboratory-bred cynomolgus monkeys: a longitudinal study during the first 6 years of life]. AB - Physical growth was studied longitudinally in laboratory-bred cynomolgus monkeys (Macaca fascicularis) aged from birth to 6.0 years in females and to 6.5 years in males. An allometric formula was applied to morphometrical growth data and the relative growth of each morphological site to anterior trunk length was analyzed. The growth patterns of all of the measurement sites in females and most of the sites in males showed monophasic allometry; while those of head length, head breadth and morphological upper face length in males were judged to show diphasic allometry. The growth patterns of morphological total face length, upper arm length and lower arm length in some males showed diphasic allometry. Morphological measurements with negative allometry were head length, head breadth, morphological total face length, total head height, biacrominal breadth hand length and foot length, while the other morphological measurements revealed isometry in both sexes. However, the values of the relative growth coefficient to anterior trunk length were larger in males than in females, except for in the case of biiliac breadth. These differences in growth patterns may cause the morphological differences between genders after sexual maturation in this primate species. PMID- 8354368 TI - Effects of soft X-ray irradiation on ocular development in Sprague-Dawley rats. AB - Pregnant rats were irradiated with soft x-rays at a dose of 1.6, 3.2, 6.3 or 12.6 Gy on Day 9 of gestation, and the eyes of F1 offspring were examined using indirect ophthalmoscopy and biomicroscopy during Postnatal Week 5. Ophthalmoscopic examination revealed iris and choroidal coloboma, microphthalmia and anophthalmia in the 3.2, 6.3 and 12.6 Gy groups. In addition to those anomalies, lens luxation and associated anterior displacement of the vitreous face, and retinal vascular anomalies were observed in the 12.6 Gy group. Histological examination revealed agenesis of retinal vessels. Ophthalmoscopic examination using biomicroscopy and indirect ophthalmoscopy detected choroidal coloboma, lens and vitreous luxation and defect in retinal vessels which could not be detected by external observation, demonstrating the usefulness of this technique in the postnatal stage of teratology studies. PMID- 8354369 TI - [Comparison of sexual behavior patterns in small laboratory animals]. AB - It is known that in the reproductive systems, aged-related changes are prominent. Similarly, in normal nonhuman primates and other mammals such as rats, various sexual activities of male and female decline with aging. The purpose of the present study was to clarify the pattern of sexual behavior in matured mice, voles, Syrian hamsters, rats, guinea pigs, rabbits and house musk shrews of both sexes, and to select the appropriate animals for studies of aged-related changes in sexual behavior. There were species differences among laboratory animals in the pattern of sexual behavior. In summary, hamsters and rats ejaculated about three times during 30 min, while mice did once during 10 hrs. The former animals showed the intromission and ejaculation within a few min and 10 min, respectively, the latter did the ejaculation a few hrs after introduction of a heat female. In female animals, rats displayed receptive and proceptive behaviors, while hamsters and guinea pigs did only receptive behavior. From the above results, rats of both sexes may be recommended for studies of aged-related changes in sexual behavior. PMID- 8354370 TI - Production of transgenic rats using pregnant and pseudopregnant rats prepared at a breeding farm. AB - We used pregnant and pseudopregnant Wistar-Imamichi rats, prepared at a breeding farm, for production of transgenic rats. The donor and recipient rats were transported to our facility for ova manipulation and embryo implantation, respectively. As a foreign gene, 1.9 kb of a hybrid gene was constructed with the rat renin promoter and chloramphenicol acetyltransferase-coding gene. Fertilized oocytes were collected from the donor and the foreign DNA was microinjected into the pronuclei of 539 oocytes by the method of Hochi. The manipulated oocytes were cultured to the 2-cell stage. One hundred seventeen 2-cell embryos were implanted in the recipient rats. Of 67 newborns, 55 rats grew up to be 3-week-old weanlings. Genomic DNA was extracted from the tail of these weanlings and examined by polymerase chain reaction analysis. Six transgenic rats were found to have been generated by the present method. In this way, transgenic rats were produced by an efficient combination of breeding farm utilization and laboratory research. PMID- 8354371 TI - [Cryopreservation of transgenic mouse embryos by ultrarapid freezing]. AB - Two transgenic mice lines were produced by introducing the rat GH antisense transgene and the chicken beta-actin promoter/firefly luciferase hybrid gene in our laboratory. We cryopreserved the transgenic embryos, obtained by fertilization in vitro with the sperm of hemizygous males for the transgene, by the ultrarapid freezing. The survival rates of cryopreserved 2-cell embryos were high (> 70%) at thawing in both lines and 53% and 16% of cryopreserved 2-cell embryos, respectively, developed to live young after transferring to oviducts of recipients. Each transgene was detected at about 40% of the live young from two transgenic lines. These results indicated that the cryopreservation of embryos by ultrarapid freezing was valuable for sustaining transgenic mouse lines without genetic contaminations. PMID- 8354372 TI - [Comparison of glutathione peroxidase activity in erythrocytes and certain tissues between voles and mice]. AB - Glutathione peroxidase (GSH-Px) activities in erythrocytes and certain tissues were investigated in herbivorous voles and C57BL/6J mice. In both voles and mice, GSH-Px activities in liver, kidney and erythrocyte were higher than those of the other tissues, such as adipose tissue, pancreas and skeletal muscle. Voles showed lower GSH-Px activities in liver, kidney, erythrocyte and brain compared with mice. PMID- 8354373 TI - Contraceptive efficacy of the diaphragm, the sponge and the cervical cap. AB - A reanalysis of data from two clinical studies--in which 1,439 women were randomly assigned to use either the contraceptive sponge or the diaphragm and 1,394 women were randomly assigned to use either the cervical cap or the diaphragm--found first-year probabilities of failure during typical use of 17% for the sponge, 18% for the cervical cap and 13-17% for the diaphragm. The first year probabilities of failure during perfect use are 11-12% for the sponge, 10 13% for the cervical cap and 4-8% for the diaphragm. The probability of failure during perfect use is significantly higher among women who have given birth than among those who have not for users of the sponge (19-21% vs. 9-10%) and users of the cervical cap (26-27% vs. 8-10%), but not for users of the diaphragm. PMID- 8354374 TI - Changes in adolescent males' use of and attitudes toward condoms, 1988-1991. AB - Data from more than 1,000 sexually active young males interviewed in 1988 for the National Survey of Adolescent Males at ages 15-19 and reinterviewed in 1990-1991 at ages 17-22 show that as the respondents grew older, their condom use declined. Although respondents' attitudes about the effects of condoms on pregnancy risk, partner appreciation, sexual pleasure and embarrassment became more favorable toward condom use over time, their degree of worry about AIDS and their perceived likelihood of getting AIDS declined. When data on males aged 17.5-19 in each time period were contrasted, the level of condom use was found to be essentially constant. Several condom-related attitudes among this age-group had become more favorable, although their perceived risk of acquiring AIDS had diminished. Multivariate analyses revealed that decreased worry about AIDS and increased denial of the seriousness of AIDS were modestly associated with a decline in condom use. Change in condom use was also affected by change in perceived reduction in sexual pleasure and by female partner's appreciation of condom use. PMID- 8354375 TI - Exploring norms and beliefs related to AIDS prevention among California Hispanic men. AB - A focus-group study gathered qualitative information from Hispanic males in California regarding ethnic factors that might enhance or interfere with AIDS prevention efforts. A predominantly working-class convenience sample of 75 men aged 18-40 participated in seven groups of 10-12 participants each. Three groups were composed of single men, three of married men and one was composed of homosexual and bisexual men. Four groups included only participants born outside the United States; and Spanish was the preferred language in five of the groups. Evaluation of the discussions indicates that while AIDS awareness is high among this population, condom use is sporadic. Few participants knew that someone infected with the human immunodeficiency virus could appear healthy; most believed they could easily determine if a woman is risky by her appearance or social standing. Although many participants thought HIV could be transmitted through casual contact, the homosexual and bisexual men were more likely to acknowledge that they were at some risk of infection; most of the heterosexual men did not perceive themselves as being at risk, even those who engaged in sex with prostitutes or women they met at bars. The participants had ambivalent attitudes toward women who suggested condom use and were often reluctant to initiate condom use themselves. Religion did not seem to play a major role in the men's attitudes about AIDS, sexuality and condom use. PMID- 8354376 TI - Measuring public attitudes on abortion: methodological and substantive considerations. AB - Data from a 1989 CBS News/New York Times survey are used to examine the effect that the framing of questions on abortion has on estimates of what proportions of the population support various legal positions. The nationwide data and results from six state polls show that general questions with only two or three options overestimate the proportions of respondents who either favor a ban on all abortion or who would allow abortion under all circumstances. Questions that pose specific circumstances result in movement of respondents out of extreme categories and into more moderate ones. Even respondents who indicate they would favor abortion in all specific circumstances and those who favor abortion in none are likely to moderate their views when asked if they support restrictions that have been proposed in a number of states. PMID- 8354377 TI - Teenage abortion, birth and pregnancy statistics by state, 1988. PMID- 8354378 TI - Questions of balance: issues emerging from the introduction of the hormonal implant. PMID- 8354379 TI - Vasectomy and prostate cancer: more questions than answers. PMID- 8354380 TI - Do school-based clinics reduce birthrates? PMID- 8354381 TI - Do school-based clinics reduce birthrates? PMID- 8354382 TI - In vitro biosynthesis of lactase in suckling and adult rabbits. Regulatory mechanisms involved in the decline of the lactase activity. AB - Steady state forms, levels and the in vitro biosynthesis of lactase-phlorizin hydrolase (LPH) proteins have been studied in proximal and middle intestine of suckling and adult rabbits. In most adult tissues the lactase activity and the LPH protein content were low and the synthesis rate of the 200 kDa lactase precursor was reduced in comparison to suckling tissues. In a few tissues with low enzymatic activity the LPH protein content was relatively high, and high lactase synthesis occurred. In addition, the ratio (labeled lactase)/(lactase protein) was lower in the middle jejunum of the adult rabbit than in the proximal region. Both decreased synthesis of LPH precursor and increased turnover or inactivation of the enzyme may cause the decline of the lactase activity. PMID- 8354383 TI - Ruptured erythrocytes inhibit the oxidation of membranes by 15-hydroperoxy eicosatetraenoic acid. AB - In this study, the pro-oxidant effects of the hydroperoxide, 15-hydroperoxy eicosatetraenoic acid (15-HPETE), on erythrocyte membranes and the modulation of the oxidation by haem proteins released from ruptured erythrocytes have been assessed. The results indicate that ruptured erythrocytes may act as an antioxidant in protecting membranes against oxidative stress induced by hydroperoxides and that it is the oxyhaemoglobin that is the active constituent of the protective mechanism. An important feature of the mechanism is the peroxidatic action of oxyhaemoglobin and its rate of reaction with 15-HPETE. PMID- 8354384 TI - The complete amino acid sequence of a thrombin-like enzyme/gyroxin analogue from venom of the bushmaster snake (Lachesis muta muta). AB - The complete amino acid sequence of a thrombin-like enzyme with gyroxin activity isolated from the venom of the bushmaster snake Lachesis muta muta was determined by automated and DABITC/PITC microsequencing of the intact protein; fragments derived from it by separate cleavages with cyanogen bromide, iodosobenzoic acid and hydroxylamine; and peptides resulting from enzymatic digestions with trypsin, pepsin, chymotrypsin, and elastase. The protein, which is composed of 228 residues, contains four putative sites of N-linked glycosylation and exhibits significant sequence similarities with other serine proteases reported from snake venoms. PMID- 8354386 TI - Altered substrate selectivity of PKC-eta pseudosubstrate site mutants. AB - Three protein kinase C (PKC)-eta mutants were constructed in which the whole or part of the pseudosubstrate site was replaced with corresponding parts of the PKC alpha pseudosubstrate site. The resulting chimaeric kinases were compared with wild-type PKC-eta in their ability to phosphorylate a PKC-eta peptide substrate or histone. Changes in the pseudosubstrate site of PKC-eta are accompanied by changes in substrate selectivity, indicating that the substrate selectivity observed for PKC-eta is at least in part due to its pseudosubstrate site. PMID- 8354385 TI - A synthetic peptide of the N-terminus of ADP-ribosylation factor (ARF) inhibits regulated exocytosis in adrenal chromaffin cells. AB - We have investigated the role of ADP-ribosylation factor (ARF) in regulated exocytosis in digitonin-permeabilized adrenal chromaffin cells by the use of a synthetic peptide, hARF1(2-17), based on the N-terminus of the protein. hARF1(2 17) inhibited Ca(2+)-dependent but not basal exocytosis, whereas equimolar levels of other synthetic peptides were ineffective. The inhibitory effect of hARF1(2 17) was dose-dependent and half-maximal at 12 microM. GTP gamma S-induced secretion in the presence of non-stimulatory CA2+ concentrations was also inhibited by hARF1(2-17). These results point to a hitherto unsuspected role for ARF in regulated exocytosis, and the potency of the hARF1(2-17) peptide suggests that ARF is essential for exocytosis in bovine adrenal chromaffin cells. PMID- 8354387 TI - Determination of renal clearance of neopterin by a pharmacokinetic approach. AB - Pharmacokinetic modelling was used to determine the glomerular filtration rate and tubular secretion of neopterin, a marker for cellular immune activation. The method involves parameter identification employing the transient venous plasma concentration profiles of marker substances. By combined i.v. injection of neopterin and inulin which is excreted exclusively via glomerular filtration, neopterin was shown to be excreted in addition to glomerular filtration, by tubular secretion: clearance of inulin, 112 (S.D. 2.2) ml/liter; clearance of neopterin, 499 (S.D. 79.7) ml/min. A pilot experiment using in addition p-amino hippuric acid suggests that neopterin and p-amino hippuric acid may employ the same carrier system for tubular secretion. PMID- 8354388 TI - Human insulin gene enhancer-binding proteins in pancreatic alpha and beta cell lines. AB - Electrophoretic mobility shift assays were performed using oligonucleotides corresponding to known protein binding sites within the human insulin gene enhancer and nuclear extracts from mouse pancreatic alpha and beta cell lines. The results demonstrate that a previously described factor, IUF-1, binds to three sites at -82 (the CT1 box), -215 (the CT2 box), and -319 (the CT3 box) in the human insulin gene enhancer. IUF-1 was present only in beta but not in alpha cells, while all other DNA-binding proteins were present in both cell lines. IUF 1 may therefore be an important determinant of insulin gene beta cell-specific expression. PMID- 8354389 TI - Pseudo-symmetrical difluoroketones. Highly potent and specific inhibitors of HIV 1 protease. AB - A series of novel, pseudo-symmetrical difluoroketones which are highly potent inhibitors of the HIV-1 protease (IC50 = 1.55-0.02 nM) were synthesized. These compounds also possess good antiviral activity by inhibition of the cytopathic effect of HIV-13B in MT-4 cells in vitro. PMID- 8354390 TI - Cloning of a human liver UDP-glucose pyrophosphorylase cDNA by complementation of the bacterial galU mutation. AB - A human liver cDNA clone which encodes the UDP-glucose pyrophosphorylase was isolated by complementation of a bacterial galU mutant. The deduced amino acid sequence of the human enzyme comprised 508 amino acids with a calculated molecular mass of 56,950. The human enzyme significantly resembles those of potato tuber and slime mold with a homology of 46.6% and 43.2%, respectively, in amino acid sequence. No homology was found between the eukaryotic and the prokaryotic enzymes. Northern blotting analysis revealed that the gene was expressed at the highest level in skeletal muscle, followed by liver, heart and kidney. PMID- 8354391 TI - Mutations in beta-actin: influence on polymer formation and on interactions with myosin and profilin. AB - Two beta-actin mutants, one with proline 38 replaced with alanine (P38A) and the other with cysteine-374 replaced with serine (C374S), as well as the wild-type beta-actin, were expressed in the yeast, S. cerevisiae, purified to homogeneity, and analyzed in vitro for polymerizability and interaction with DNase I, myosin, and profilin. Both mutations interfered with the polymerization of the actin, and with its interaction with myosin. The C374S mutation had the most pronounced effect; it reduced the polymerizability of the actin, abolished its binding to profilin, and filaments containing this mutation moved at reduced rates in the in vitro 'motility assay'. The ATPase activity measured in solutions containing myosin subfragment 1 was similar for both the mutant and wild-type actins. PMID- 8354392 TI - Skin L-tryptophan-2,3-dioxygenase and rat hair growth. AB - We have identified a new enzyme, skin L-tryptophan-2,3-dioxygenase (skin TDO), that catalyzes the degradation of L-tryptophan into formylkynurenine in rats. The rate of this degradation peaks in all rats at 5 to 6 weeks after birth, and also, among rats depilated at 8 weeks old, at 10 to 11 weeks after birth. We have also observed that the properties of this enzyme are closer to those of hepatic L tryptophan-2,3-dioxygenase (hepatic TDO) than to indoleamine 2,3-dioxygenase. Although an intraperitoneal injection of L-tryptophan increased the activity of skin TDO to approximately 2.2 times greater than control values, an intraperitoneal injection of hydrocortisone and alpha-methyl-DL-tryptophan, both compounds known to affect hepatic TDO activity, had no effect on skin TDO activity. The molecular weight of skin TDO was estimated to be 16.0 kDa, which is close to the molecular weight of hepatic TDO, yet a much larger molecule than indoleamine-2,3-dioxygenase. Increased hair growth rates paralleled increased levels of skin TDO activity in 5- to 6-week-old rats, and marked increases in the activity of skin TDO occurred 2 or 3 weeks after depilation. Enzyme activity was also greatest 2 days before the time of maximum hair root length. Therefore, skin TDO may play an important role in the initiation or suppression of rat hair growth. PMID- 8354393 TI - Elongation in a Dictyostelium in vitro translation system is affected by calmodulin antagonists. AB - We have previously shown that the Dictyostelium discoideum ribosomal protein L19 specifically binds Ca2+/calmodulin [Sonneman et al. (1991) J. Biol. Chem. 266, 23091-23096]. To investigate the role of calmodulin in the regulation of protein synthesis, we have now established an in vitro protein synthesizing system from Dictyostelium cells which can elongate polypeptide chains with high efficiency. Various calmodulin antagonists affected translation in this system. The inhibitory effects of the antagonists could be partially reversed by addition of calmodulin. A monoclonal antibody against D. discoideum calmodulin also specifically inhibited protein synthesis. Similar effects of calmodulin antagonists were found in a standard wheat germ in vitro translation system. PMID- 8354394 TI - Up-regulation of system A activity in the regenerating rat liver. AB - System A activity for neutral amino acid transport, measured as the MeAIB sensitive Na(+)-dependent L-alanine uptake, is induced 6 h after partial hepatectomy in plasma membrane vesicles from rat livers. Other Na(+)-dependent transporters, like system ASC (MeAIB-insensitive Na(+)-dependent L-alanine transport) and the nucleoside carrier show similar inductions. Up-regulation of system A is not explained by changes in the dissipation rate of the Na+ transmembrane gradient, as deduced from uptake measurements performed in the presence of monensin. To determine whether induced system A shared any similarity with the activity found in hepatoma cell lines, we analyzed the N-ethylmaleimide (NEM) sensitivity of system A in both regenerating and control rat liver plasma membrane vesicles. NEM treatment was equally effective in inhibiting system A in both experimental groups. Thus, during the prereplicative phase of liver growth, a transport activity similar to basal system A is up-regulated in liver parenchymal cells, by a stable mechanism that does not involve changes in the Na+ transmembrane gradient. PMID- 8354395 TI - Evidence for a distinct H7-resistant form of protein kinase C in rat anterior pituitary gland. AB - Inhibition of phorbol 12,13-dibutyrate-induced protein kinase C (PKC) activity from rat midbrain, anterior pituitary and a number of other tissues, as well as COS 7 cells, was studied in vitro. In anterior pituitary, Ca(2+)-independent activity was notably resistant to H7 but sensitive to staurosporine and Ro 31 8220. All Ca(2+)-dependent activity was sensitive to these three inhibitors. Mezerein and 1,2-dioctanoyl-sn-glycerol also activated this H7-insensitive PKC from anterior pituitary. The distribution of this activity, prominently expressed in pituitary and perhaps also lung, and its characteristic resistance to H7 but not other inhibitors, does not obviously correlate with that of any of the well characterised PKCs, and may reflect either a novel or a modified isoform. PMID- 8354396 TI - Kinetics of glucose oxidase catalyzed electron transfer mediated by sulfur and selenium compounds. AB - Unusually high electron transfer rates in Aspergillus niger glucose oxidase catalyzed oxidation of glucose using 5,6:11,12-Bis(dithio)tetracene (TTT), 1,2 dimethyltetraselenafulvalene (DMTSF) and tetrathiafulvalene (TTF) were observed. At pH 7.0 oxidation rate constants (TN/Km) in the range from 1.0.10(7) to 8.7.10(7) M.s-1 were deduced from experimental data. One of the investigated mediators, DMTSF, has been used for electrocatalytical glucose oxidation on graphite at a potential of 0.3 V vs. a standard calomel electrode (SCE). The prepared bioelectrodes have a sensitivity of 1.3 microA/(cm2.mM), a pH optimum at 6.5-7.0, and a linear range which covers the relevant range for monitoring physiological levels of glucose. The bioelectrodes are stable for more than one month. PMID- 8354397 TI - Ionic bases of the membrane potential and intracellular pH changes induced by speract in swollen sea urchin sperm. AB - Signal transduction initiated by the egg peptide, speract, in sea urchin sperm is not fully understood. Hypotonically swollen sperm are a suitable model to study peptide signal transduction. Ion substitution experiments now indicate (i) that the permeability to Na+, Ca2+, and Mg2+ contributes to the sperm resting membrane potential; (ii) the repolarization induced by nM concentrations of speract is Na+ dependent and mediated by an as yet unidentified channel; (iii) the depolarization triggered by nM concentrations of speract involves Ca2+ channels since it is Ca(2+)-dependent and blocked by Co2+ and Ni2+, two Ca2+ channel blockers; (iv) hyperpolarizing swollen sperm with valinomycin increases intracellular pH (pHi) in the same way as speract, thus the speract-induced hyperpolarization may be responsible for the pHi increase. PMID- 8354398 TI - High molecular weight aspartic endopeptidase generates a coronaro-constrictory peptide from the beta-chain of hemoglobin. AB - Studying the influence of brain cathepsin D (EC 3.4.23.5) and high molecular weight (HMW) aspartic endopeptidase (EC 3.4.23.-) on the processing of hypothalamic calmodulin-binding coronaro-constrictory peptide factors from the beta-chain of globin it was found that only HMW aspartic endopeptidase generates the fragment 31-40 of the beta-chain of bovine hemoglobin (Hb) by cleavage of the Leu30-Leu31 and Phe40-Phe41 bonds. Digestion of the beta-chain of globin was performed at 37 degrees C at an enzyme/substrate ratio of 1:80 at pH 3.5 using different times of incubation (from 4 h to 10 h). The resulting peptides were separated by reversed-phase high-performance liquid chromatography (HPLC) and then identified by amino acid analysis and Edman degradation. The differences in specificity and activity of these two brain aspartic proteinases could be explained by their different structural features. Our finding provides evidence for a different biological function of these two enzymes. Data obtained give us reason to suppose that HMW aspartic proteinase probably can participate in the processing of the coronaro-constrictory peptide in vivo by limited proteolysis of Hb or Hb-like protein. PMID- 8354399 TI - The C-terminal region of the S component of staphylococcal leukocidin is essential for the biological activity of the toxin. AB - The Staphylococcal toxin leukocidin consists of two protein components, F and S. From a culture medium of Staphylococcus aureus RIMD 310925, we isolated a truncated form of S (LS2), of which the C-terminal 17-residue segment is missing. Unlike intact S, LS2, showed neither leukocytolytic activity in the presence of F nor affinity for monosialoganglioside GM1 (GM1). When excited at 280 nm, both S and LS2 exhibited intrinsic tryptophan fluorescence with an emission maximum at 318 nm. Upon binding to GM1, the emission maximum of S underwent a blue shift to 310 nm, whereas no change in fluorescence took place on mixing GM1 with LS2. We conclude that the C-terminal region of S is essential for its biological activity as well as for its binding to GM1 and that this binding is accompanied by a conformational change of the S protein. PMID- 8354400 TI - Receptor phage. Display of functional domains of the human high affinity IgE receptor on the M13 phage surface. AB - In this paper we demonstrate that phage display technology is a suitable system for studying the interaction between the high-affinity receptor for IgE (Fc epsilon RI) and IgE. The alpha subunit extracellular domains of the human receptor were expressed on the surface of filamentous phage M13 fused to the carboxyl-terminal part of the gene III protein (pIII). Two constructs were made, the first with both the Ig-like domains of the receptor alpha chain and the second with only the C-terminal domain. The fusion genes were cloned in a phagemid vector to display monovalently the receptor on the phage surface. Our results indicate that the alpha receptor expressed on the phage is able to interact with IgE as demonstrated by an ELISA assay. In addition, by using the same system, we show that a single domain of the alpha receptor is sufficient for the interaction with IgE although with a binding affinity lower than that of the two-domain receptor. PMID- 8354401 TI - A rapid and efficient purification method for recombinant annexin V for biophysical studies. AB - Annexin V binds in a calcium-dependent manner to acidic phospholipids and exhibits ion channel activity in vitro. We are investigating mutants of annexin V by single channel measurements, X-ray crystallography and electron microscopy in order to understand the structure-function relationships of the ion channel activity. We describe here a method to obtain very pure recombinant annexin V required for such studies. The initial step is the mild opening of the bacterial cells by an osmotic shock. In the purification procedure, use is made of the reversible calcium-mediated binding of annexin V to liposomes. In the last purification step the protein is subjected to ion-exchange chromatography and elutes as a single peak free of any detectable contaminants. PMID- 8354402 TI - Structure of three acidic O-linked carbohydrate chains of porcine zona pellucida glycoproteins. AB - Structural analysis by 1D and 2D 1H NMR spectroscopy of three acidic O-linked oligosaccharide alditols, released from porcine zona pellucida glycoproteins by alkaline borohydride treatment, afforded the following structures: Gal beta 1 4(6SO4)GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-3GalNAc- ol Neu5Gc alpha 2-3Gal beta 1-4(6SO4-)GlcNAc beta 1-3Gal beta 1- 4GlcNAc beta 1-3Gal beta 1 3GalNAc-ol Neu5Ac alpha 2-3Gal beta 1-4(6SO4-)GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1- 3Gal beta 1-3GalNAc-ol These oligosaccharides are the smallest compounds that contain the structural elements which are present in the acidic, high molecular mass O-linked carbohydrate chains of porcine zona pellucida glycoproteins. PMID- 8354403 TI - Two-step epoxidation of hyoscyamine to scopolamine is catalyzed by bifunctional hyoscyamine 6 beta-hydroxylase. AB - In several solanaceous plants, hyoscyamine is first hydroxylated at the 6 beta position, and then epoxidized to scopolamine. We expressed hyoscyamine 6 beta hydroxylase (H6H) in Escherichia coli as a fusion protein with maltose-binding protein. The crude cell extract from the bacterium that expressed the soluble fusion protein showed a strong hydroxylase activity and a weak epoxidase activity. When 100 microM of hyoscyamine was fed to the recombinant bacterium, the alkaloid was first converted to 6 beta-hydroxy hyoscyamine, and then to scopolamine, which was almost the only alkaloid found in the culture after one week. Therefore, H6H catalyzes two consecutive reactions that oxidize hyoscyamine to scopolamine. PMID- 8354404 TI - Peptide synthesis by chymotrypsin in frozen solutions. Free amino acids as nucleophiles. AB - Nucleophilic efficiency of the free amino acids in chymotrypsin-catalyzed acyl transfer in ice at -18 degrees C using ethyl esters of N-maleyl-L-tyrosine and L tyrosine as the acyl group donors has been studied. Although the amino acids did not act as acyl acceptors in liquid water, the high yields of peptides were obtained in frozen solutions at pH 10.5 (before freezing). The efficiency of amino acids in the formation of the corresponding dipeptides depended on the substrate used, and decreased in the order Ser,Thr,Gln > Lys > Cit > Ala > Ala > Gly > Asn > Arg > Glu > Val > Orn > Asp with no peptide formed with His, Leu, Ile and Pro) for N-maleyl-L-tyrosine ethyl ester and Ser > Lys > Orn > Arg,Cit > Gln > Thr > Asn > Ala > Gly (with no peptide formed with Glu, Val, Asp, His, Leu, Ile and Pro) for L-tyrosine ethyl ester. PMID- 8354405 TI - Metribuzin resistance in photoautotrophic Chenopodium rubrum cell cultures. Characterization of double and triple mutations in the psbA gene. AB - Sequence analysis of eight metribuzin-resistant mutants of photoautotrophic Chenopodium rubrum cell cultures revealed new mutations in the psbA gene coding for the 32 kDa herbicide binding protein. Mutants were found to possess either two or three changes in the amino acid sequence of the D1-protein between positions 219 and 272. PMID- 8354406 TI - Yeast mitochondrial ATP-dependent protease: purification and comparison with the homologous rat enzyme and the bacterial ATP-dependent protease La. AB - Homogenous ATP-dependent protease has been isolated for the first time from mitochondria of yeast Saccharomyces cerevisiae. The enzyme molecule consists of six 120 kDa subunits. It is a serine protease with an absolute ATP requirement for its activity. Basic enzymatic characteristics of the yeast protease are similar to those of the corresponding rat mitochondrial enzyme and of the E. coli protease La. The yeast enzyme immunochemically cross-reacts with the bacterial protease La. PMID- 8354407 TI - High-resolution XANES studies on vanadium-containing haloperoxidase: pH dependence and substrate binding. AB - High-resolution X-ray absorption vanadium K-edge spectra were recorded for samples of vanadium-containing bromoperoxidase from the brown alga, Ascophyllum nodosum, at pH 9, 7, 5 and 4, as well as for enzyme samples containing the substrates, hydrogen peroxide and bromide. The well-resolved features of the XANES spectra are discussed. The pH-dependence of the structure of the active site has been studied revealing no significant change of the absorption features. We were able to detect an interaction of H2O2 with the vanadium site of the bromoperoxidase using XAS spectroscopy, whereas addition of bromide causes no energy shift of the XANES spectrum. The possible role of vanadium during the enzymatic reaction is discussed on the basis of our results. PMID- 8354408 TI - Trehalose-6-phosphate, a new regulator of yeast glycolysis that inhibits hexokinases. AB - Trehalose-6-phosphate (P) competitively inhibited the hexokinases from Saccharomyces cerevisiae. The strongest inhibition was observed upon hexokinase II, with a Ki of 40 microM, while in the case of hexokinase I the Ki was 200 microM. Glucokinase was not inhibited by trehalose-6-P up to 5 mM. This inhibition appears to have physiological significance, since the intracellular levels of trehalose-6-P were about 0.2 mM. Hexokinases from other organisms were also inhibited, while glucokinases were unaffected. The hexokinase from the yeast, Yarrowia lipolytica, was particularly sensitive to the inhibition by trehalose-6-P: when assayed with 2 mM fructose an apparent Ki of 5 microM was calculated. Two S. cerevisiae mutants with abnormal levels of trehalose-6-P exhibited defects in glucose metabolism. It is concluded that trehalose-6-P plays an important role in the regulation of the first steps of yeast glycolysis, mainly through the inhibition of hexokinase II. PMID- 8354409 TI - A role for iron in transcriptional activation by FNR. AB - FNR is a transcriptional regulator which controls the expression of target genes in response to anoxia in Escherichia coli. The mechanism by which FNR senses and responds to anaerobiosis is unknown but indirect evidence suggests that an iron cofactor is involved. Using KMnO4 as a probe for DNA melting at active promoters, footprinting studies have now shown that the ferrous iron chelator, ferrozine, inhibits open complex formation in vivo, and that FNR with a high iron-content is essential for open complex formation in vitro. Since open complex formation is an essential pre-requisite for transcription, it is concluded that transcriptional activation by FNR is mediated by a ferrous iron cofactor. PMID- 8354410 TI - Molecular mechanism of inhibition of mammalian protein synthesis by some four chain agglutinins. Proposal of an extended classification of plant ribosome inactivating proteins (rRNA N-glycosidases). AB - The four chain agglutinins from Abrus precatorius, Viscum album and Ricinus communis promote depurination of the 28 S rRNA from rabbit reticulocyte ribosomes characteristic of the common ribosome-inactivating proteins (RIPs). These agglutinins inhibited mammalian protein synthesis at nanomolar concentrations but they do not affect plant protein synthesis under the same conditions. Therefore, they should also be considered as true RIPs but of a new class, the four-chain RIPs. An extended classification of RIPs is presented based on the former one from Stirpe et al. [Bio/technology 10 (1992) 405-412]. PMID- 8354411 TI - Arachidonic acid abolishes the mitogen-induced increase in cytosolic free Ca2+ and intracellular pHi in rat thymocytes. AB - The effects of arachidonic acid (AA) and the lectin mitogens, concanavalin A (Con A) and phytohemagglutinin (PHA), on [Ca2+]i and pHi in rat thymocytes have been studied by using the intracellular fluorescent probes, Fura-2 and BCECF. It was revealed that exogenous AA (3 microM), in addition to the well-known changes in basal [Ca2+]i and pHi, also caused a complete blockade of [Ca2+]i and pHi signals induced by Con A (10 micrograms/ml) and PHA (10 micrograms/ml). In contrast, exposure of thymocytes to mitogens did not prevent the AA-induced increase in [Ca2+]i and decrease in pHi. In experiments with sodium propionate, the similarity between AA action and EIPA (ethylisopropylamiloride), an inhibitor of Na+/H+ exchangers, was revealed. It is proposed that the inhibitory effect of AA on mitogen-induced lymphocyte proliferation is due primarily to the blockade of transmembrane [Ca2+]i and pHi signals, associated with a sustained cytosolic acidification. PMID- 8354412 TI - Identification of a novel high-affinity binding site for N acetylchitooligosaccharide elicitor in the membrane fraction from suspension cultured rice cells. AB - Binding experiments using a 125I-labeled tyramine conjugate of N acetylchitooctaose, a highly potent elicitor for the induction of phytoalexin production in rice cells, and a microsomal membrane preparation from suspension cultured rice cells showed the presence of a novel high-affinity binding site for this oligosaccharide. The binding of the ligand was saturable and the Scatchard plot analysis of the results indicated the presence of a single class of binding site with a Kd of 5.4 nM which is comparable with that reported for the binding of the hepta-beta-glucoside elicitor in soybean membrane. The ligand binding was inhibited by unlabeled N-acetylchitoheptaose but not by its deacetylated form. These characteristics of this binding site coincide well with the specificity and sensitivity for the elicitor in several assay systems, suggesting the possible involvement of this binding site in the recognition of the elicitor in vivo. PMID- 8354413 TI - Association of annexin V with mitochondria. AB - Annexin V is an intracellular protein recently shown to be localized to nucleoli and cytosol. In this study we show that cytosolic annexin V is associated with mitochondria. To assess the nature of the annexin V-mitochondrial interaction, an annexin V binding activity was partially purified from placental cytosol by annexin V-affinity chromatography. Five polypeptides in the eluate appeared to be associated with annexin V, with a predominant species of 27 kDa. Antibodies to the 27 kDa polypeptide recognised mitochondria but not nucleoli. We conclude that annexin V interacts with a 27 kDa mitochondrial polypeptide that is possibly part of a larger complex. PMID- 8354414 TI - Use of bimanyl actin derivative (TMB-actin) for studying complexation of beta thymosins. Inhibition of actin polymerization by thymosin beta 9. AB - By reacting trimethylammoniobromobimane bromide (TMB bromide) with rabbit muscle actin, a fluorescent reporter group was linked to cysteine at position 374. Fluorescence of TMB-actin decreased significantly on addition of thymosin beta 4 (T beta 4), a peptide of 43 amino acid residues reported to bind to monomeric actin and to prevent filament formation. Based on this effect, we determined the KD value of the thymosin beta 4 complex as 0.8 microM, a value that is in agreement with previous determinations. In addition to the main compound thymosin beta 4, bovine tissue contains a related peptide, thymosin beta 9 (T beta 9), which has 41 amino acid residues and ca. 75% sequence homology. In the present study we show for the first time that T beta 9, similar to T beta 4, forms a 1:1 complex with monomeric actin, and hereby inhibits actin polymerization. With a KD value of 1.1 microM the affinity of T beta 9 is in the same range as that of T beta 4, suggesting that T beta 9, like T beta 4, contributes to maintaining the pool of monomeric actin in bovine non-muscle cells. Further proof of the interaction of T beta 9 with actin was provided by native PAGE, where the complex showed the reported higher mobility, as well as by crosslinking experiments. Using different crosslinking reagents, like water-soluble carbodiimide (EDC), m maleimidobenzoyl-N-hydroxysuccinimidate (MBS), and disuccinimidylsuberate (DSS), we were able to produce conjugates of 47 kDa. In one of these (from MBS) both actin and T beta 9 could be identified by immunoblotting. When, in the MBS crosslinking experiments, native actin was replaced with (374-NEM)-actin, the 47 kDa band was not seen, indicating that Cys-374 takes part in the thiol-specific crosslinking reaction. This suggests that part of the binding site of T beta 9 must be located close to the carboxy-terminus. PMID- 8354415 TI - Cell-specific expression of Gq/11 protein and mRNA in rat seminiferous tubules. AB - As part of a study to elucidate the involvement of G proteins in signal transduction in testicular cells, we have examined the cellular localization of Gq/11 within the seminiferous tubules. The somatic cells (Sertoli cells, peritubular cells) contain high amounts of both Gq/11 alpha mRNA and immunoreactive protein. In contrast, very low levels of these G proteins and the corresponding mRNAs are present in the germ cells (pachytene spermatocytes, round spermatids). Thus, in the germ cells, receptor-regulated inositol phospholipid hydrolysis is not likely to be regulated via Gq/11, but rather through the Go protein, which has been previously shown to be abundant in rat germ cells. Since the somatic cells are nearly devoid of Go, the Gpp(NH)p-stimulated phospholipase C in these cells is probably regulated by Gq and/or G11. PMID- 8354416 TI - Nephrotic syndrome associated with Schistosoma mansoni infection. AB - A case of nephrotic syndrome in which Schistosoma mansoni infection associated with membranoproliferative glomerulonephritis type 1 is reported. In endemic areas glomerulopathy secondary to Schistosoma mansoni has been described. Although not commonly seen in mainland United States, Schistosoma mansoni infection should be considered in the differential diagnosis of proteinuria in persons who have visited or are from endemic regions. PMID- 8354417 TI - Fatal injury surveillance report, Delaware, 1990. Head and spinal cord injuries. AB - The Delaware Disabilities Prevention Program is funded through a five-year Centers for Disease Control and Prevention (CDC) grant to prevent primary and secondary disabilities associated with mental retardation and low socioeconomic status; head and spinal cord injuries; and sickle cell disease. This report focuses on fatal head and spinal cord injuries. Death certificates and autopsy reports from 1990 were the data sources used for this study. In 1990, 122 fatal head injuries and 20 fatal spinal cord injuries occurred among Delaware residents. Eight of these individuals experienced both head and spinal cord injuries. Motor vehicle crashes caused the majority of both head and spinal cord deaths. Suicides, homicides, and falls were the other major causes of fatal head injuries. Deaths are only the tip of the injury iceberg. Head and spinal cord injuries can cause lifelong disabilities affecting family, friends, and the entire community. PMID- 8354418 TI - Sexual misconduct in the physician-patient relationship. PMID- 8354419 TI - Computers in medicine. PMID- 8354420 TI - Through the looking glass. PMID- 8354421 TI - Clarification of access to patient records. PMID- 8354422 TI - Teachers should follow school no smoking rule. PMID- 8354423 TI - Paramedic standing orders. PMID- 8354424 TI - Intrauterine position effects on sexually dimorphic asymmetries of Mongolian gerbils: testosterone, eye opening, and paw preference. AB - A series of experiments was undertaken to both discover and explore the causes of sexually dimorphic phenotypic asymmetries in infant and adult Mongolian gerbils. We found that (1) the order in which the eyes of individual gerbil pups opened varied with their gender; right eyes of female pups opened before left eyes, while left eyes of male pups opened before right eyes, and (2) the paw that adult gerbils held in the air while maintaining a species-typical tripedal stance varied with gender; female gerbils held their right paws in the air significantly more often than did male gerbils. Both order of eye opening and laterality of paw use while in a tripedal stance varied significantly as a function of the intrauterine position which subjects had occupied as fetuses. These data implicate exposure to testosterone as a mediator of the development of asymmetries exhibited by Mongolian gerbils. PMID- 8354425 TI - Body scale and infant grip configurations. AB - This study examined whether hand/object size ratios define common boundaries to the grip configuration patterns of infants and adults. A group of 5- to 8-month old infants and a group of adults engaged in a displacement grasping task with inverted cups that varied in size. The findings showed that infant and adult grip configurations varied systematically with object size: More digits were brought into the contact grip configurations with increasing object size. Furthermore, when object size was scaled to hand size, common dimensionless ratios defined the grasping patterns and transitions between grasping patterns in a similar manner for both adults and infants. Consistent with a dynamical view of the development of coordination, the strong role of body scale on the developmental prehensile coordination pattern was observed for a given set of task constraints. PMID- 8354426 TI - Individual differences in the visual attention of human infants: further evidence for separate sensitization and habituation processes. AB - How many and what kinds of processes mediate infant visual attention? Are they influenced by stimulus "complexity?" Analyses were performed on visual fixation data from ninety 4-month-old infants; the time each infant spent looking at a black and white checkerboard pattern containing either 4 x 4, 12 x 12, or 20 x 20 checks per picture was measured for eight 10-s trials, with 10-s interstimulus intervals (Kaplan & Werner, 1986). Correlational and factor analyses revealed one significant source of individual variability (or factor) in the 4 x 4 data, and two significant sources in the 12 x 12 and 20 x 20 data. One factor gained strength over progressive trials and accounted for decreases in looking time. A second factor gained strength over the first few trials, then lost strength over the remaining trials, and accounted for initial increments in looking time. The two factors are consistent with a dual-process model of infant response dynamics; the first may represent habituation, a decremental process, and the second may represent sensitization, an incremental process that is activated by "complex" stimuli. PMID- 8354427 TI - Hemispheric specialization in infant chimpanzees (Pan troglodytes): evidence for a relation with gender and arousal. AB - The current study extends previous documentation of behavioral asymmetries in hand-to-mouth, self-consoling behaviors of infant chimpanzees. The underlying source of lateralized hand-to-mouth, self-calming behavior was investigated by comparing individual differences in neonatal arousal levels, regulatory ability, and motor performance with individual differences in the degree of laterality at 3 months. Asymmetrical hand-to-mouth, self-calming behaviors at 3 months of age were significantly related to general arousal at 2 days of age (i.e., the Range of State cluster scores measured by the Brazelton Neonatal Behavioral Assessment Scale). Simply stated, chimpanzees with a right-hand bias in hand-to-mouth behavior exhibited lower arousal at 2 days of age compared with nonright-handed individuals. The only item of the Range of State cluster to distinguish subjects was irritability: Right-handed subjects were less irritable. Previously, a trend was reported with respect to sex differences in the laterality of hand-to-mouth behavior. With the greater number of subjects in the present study, we found that females exhibited a significantly greater right-hand bias for hand-to-mouth behaviors (12 of 13) than did males (9 of 15). We conclude that neonatal arousability, and not regulatory capacity or motor performance, predicts the degree of laterality found in hand-to-mouth, self-calming behaviors in 3-month old chimpanzees. These data are discussed from the standpoint of early pari parturitional or intrauterine factors affecting lateralized development. PMID- 8354428 TI - Acquired disabilities: new directions. PMID- 8354429 TI - The stability of binocular fixation during reading in adults and children. AB - The authors recorded the binocular eye-movements of children and adults while they read single words appropriate for their reading ability. Normal data were obtained from nine- to 11-year-old primary-school children and adults, because very little is known about changes in binocular vergence during reading. These normal data were compared with those from poor readers of the same age who had passed or failed the Dunlop Test. On average, normal children made larger vergence errors while they fixated words than did adults. There were no differences between the groups of children, therefore the authors conclude that poor vergence control during reading fixations is not the immediate cause of the non-word error effect found among children who fail the Dunlop Test. PMID- 8354430 TI - Handedness and progressive hydrocephalus in spina bifida patients. AB - Hand preference and functional hand-dominance of 45 spina bifida patients (aged 13 to 25 years) were assessed by means of self-reports on an ordinal scale and a tapping task. Non-right-handedness was more frequent among patients with accompanying progressive hydrocephalus. Left-hand preference was significantly more frequent in this group than in patients without shunts. Non-right-handedness in hydrocephalic patients correlated positively with the estimated degree of pre operative progress of the hydrocephalus. The apparent failure to establish right handedness in these patients seemed to reflect a developmental disorder of lateralization, related to a more advanced degree of progressive hydrocephalus at an early age. It is suggested that the disorder may be attributable to dysfunction of the corpus callosum, caused by delay in the development of callosal white matter when the hydrocephalus is in a progressive state. PMID- 8354431 TI - Visual evoked potentials and visual processing in stimulant drug-exposed infants. AB - Prenatal exposure to cocaine and amphetamines has been associated with many adverse effects in infants, including neurological abnormalities. Recent evidence shows that the visual system may be useful in infancy to evaluate neurological functioning. Visual evoked potentials (VEPs) and visual recognition memory testing were carried out on eight infants with prenatal drug-exposure and eight controls, matched for ethnicity and socio-economic status. The drug-exposed infants performed significantly worse on the visual recognition test. However, there were no differences between groups on VEP testing and no correlations between tests. The results suggest that the difficulties found in visual recognition memory of drug-exposed infants are not related to neurological maturity, as measured by VEPs. PMID- 8354432 TI - Reliability of an index of child characteristics. AB - The ABILITIES index provides a means to describe nine areas of functional abilities and disabilities. In this study, the authors examined the agreement between ratings made by 130 parents and teachers, 130 parents and specialists, and 125 teachers and specialists. Stability of ratings was assessed by asking 40 teachers to complete the index a second time, an average of 34 days after the first rating. The results suggest that raters who vary considerably in expertise, discipline and relationship to the child generally agree as to the child's presenting characteristics. PMID- 8354433 TI - Autism and hypomelanosis of Ito in twins. AB - A pair of monozygotic and a pair of dizygotic twins with autism and hypomelanosis of Ito skin-abnormalities are described. These observations are further evidence of the frequent association between these two conditions, already demonstrated in the literature, and suggest a possibly higher incidence of single gene associations among cases of autism with known genetic basis. PMID- 8354434 TI - [Change in central hemodynamics during antiorthostatic influences in humans with varying types of blood circulation and physical preparedness]. PMID- 8354435 TI - [Electromyographic patterns of thermoregulatory activity of motor units in the process of body cooling]. PMID- 8354436 TI - [The training effect of high-frequency electric stimulation on the fast tibial anterior muscle in man. II. Effect on speed-force properties and working capacity]. PMID- 8354437 TI - [Combination of differently directed physical stresses in amateur runners: skeletal muscle adaptation and hormonal profile]. PMID- 8354438 TI - [Effect of local thermostimulation of the skin on reflex excitability of wrist flexor motor neurons]. PMID- 8354439 TI - [Differentiated secretory response of the stomach, duodenum and pancreas to test breakfasts of various composition]. PMID- 8354440 TI - [Zinc metabolism in healthy people as affected by physical exertion]. PMID- 8354441 TI - [Geometry of adaptive in biosystems]. PMID- 8354442 TI - [Status of the erythron in cadets with varyious degrees of adaptability to study in a military school]. PMID- 8354443 TI - [Emotions and their role in cognitive processes at various ontogenetic stages]. PMID- 8354444 TI - [The helium-neon laser in apex cardiography]. PMID- 8354445 TI - [Human recognition of odors as a function of previous experience]. PMID- 8354446 TI - [Hypotensive effect of biomechanical stimulation of leg muscles in man]. PMID- 8354447 TI - [Physiologic changes in aminazine syndrome, traumatic shock and alimentary dystrophy]. PMID- 8354448 TI - [Cerebral organization of emotions at various levels CNS activation]. PMID- 8354449 TI - [Regularities of the effect of acupuncture on EEG and hemodynamic parameters as a function of the initial type of circulation in hypertensive patients]. PMID- 8354450 TI - [Features of visual contrastometry in patients with basal ganglia dysfunction]. PMID- 8354451 TI - [Cognitive hypothesis of hemispheric asymmetry of human emotional functions]. PMID- 8354452 TI - [Functional state of the human nervous system at various stages of burn injury (according to recorded super-slow biopotentials]. PMID- 8354453 TI - [Non-specific factors of Pa/Nb complex formation in mid-latent auditory evoked potentials]. PMID- 8354454 TI - [Human EEG-correlates in multisided peripheral exposure to alternating magnetic field]. PMID- 8354455 TI - [Mathematical analysis of cardiac rhythm]. PMID- 8354456 TI - [Use of automated programs for comprehensive prognostic evaluation of individual adaptive potential]. PMID- 8354457 TI - [Evaluation of the adaptive potential of adolescents at various stages of puberty according to autonomic, morphometric and hormonal parameters]. PMID- 8354458 TI - Identification and sequence analysis of the replication region of the phage resistance plasmid pCI528 from Lactococcus lactis subsp. cremoris UC503. AB - The replication region of the phage resistance plasmid pCI528 from Lactococcus lactis subsp. cremoris UC503 was localised to within a 10-kb HindIII restriction fragment. A 6.3-kb BglII-HindIII subclone of this fragment, cloned into a replication probe vector, allowed replication in Lactococcus but not in Bacillus or Lactobacillus. Sequence analysis revealed an ORF of 1152 bp preceded by a putative ori region containing a 22-bp sequence tandemly repeated three and three quarter times, a second smaller direct repeat and two inverted repeats. Extensive homology was observed with the well characterised replication region of the small cryptic plasmid pCI305 (Hayes, F., Vos, P., Fitzgerald, G.F., deVos, W. and Daly, C. Plasmid 25, 16-26). PMID- 8354459 TI - Hydrogen-ubiquinone oxidoreductase activity by the Bradyrhizobium japonicum membrane-bound hydrogenase. AB - The Bradyrhizobium japonicum heterodimeric nickel-iron hydrogenase efficiently catalyzed H2-ubiquinone-1 oxidoreductase activity at rates up to 47% of the maximal rates obtained using the artificial electron acceptor methylene blue. Gel filtration chromatography and SDS-polyacrylamide gel electrophoresis experiments demonstrated that the purified enzyme was a heterodimer containing only the 65 kDa and 33 kDa subunits. Reduced minus oxidized absorption difference spectra demonstrated the absence of detectable cytochromes. The H2-ubiquinone-1 oxidoreductase activity of both the purified heterodimeric hydrogenase and membranes was significantly inhibited by 2-n-heptyl-4-hydroxyquinoline-N-oxide and antimycin A, inhibitors known to act in the quinone region of electron transport chains. Our results are the first report of H2-ubiquinone oxidoreductase activity by a purified hydrogenase. PMID- 8354460 TI - Mouse pathogenicity studies of Nocardia asteroides complex species and clinical correlation with human isolates. AB - Nocardia asteroides complex organisms derived from human specimens between 1979 and 1992 were identified to the species level. Of 117 N. asteroides complex organisms, 34 (29%) were N. farcinica, 28 (24%) were N. nova, and 55 (47%) were N. asteroides sensu stricto. An analysis of the specimen sites from which the organisms were derived showed that isolates derived from blood, brain, or bone marrow were more likely to be N. farcinica than the other two species. A study of the virulence of ten strains of each species was undertaken, using a mouse model with intravenous inoculation. The 50% lethal doses (LD50) for N. farcinica were significantly lower than those of the other two species. LD50 values for N. nova and N. asteroides were not significantly different. The above data confirming the greater virulence of N. farcinica support the identification of species within the N. asteroides complex. PMID- 8354461 TI - Trifluoperazine inhibits the incorporation of labelled precursors into lipids, proteins and DNA of Mycobacterium tuberculosis H37Rv. AB - We have recently demonstrated that the calmodulin antagonist trifluoperazine has antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv susceptible and resistant to isoniazid. It is now shown that trifluoperazine at a concentration of 50 micrograms ml-1 when added to the cells along with the labelled precursors inhibited the incorporation of [14C]acetate into lipids (63%) and uptake of [14C]glycine (74%) and [3H]thymidine (52%) by whole cells of M. tuberculosis H37Rv by 6 h of exposure. After 48 h, the inhibition was 87%, 97% and 74%, respectively. However, when the drug was added to cells taking up and metabolizing the labelled precursors at a later point (3 h for [14C]acetate and [3H]thymidine and 12 h for [14C]glycine) it inhibited completely the uptake of all the precursors, at least up to 24 h. The onset of inhibitory action was very rapid, i.e. 3 h. It is suggested that trifluoperazine has multiple sites of action and acts probably by affecting the synthesis of lipids, proteins and DNA. PMID- 8354462 TI - Purification and characterization of an 'actomyosin' complex from Escherichia coli W3110. AB - An 'actomyosin' complex was purified from Escherichia coli W3110 using selective precipitation. The complex contains three major components of 19.5, 18.5 and 17 kDa. The 19.5- and 17-kDa proteins were purified by electroelution, peptide mapped and N-terminally sequenced. The structural gene for the 17-kDa protein was found to have been previously identified in an operon containing several other genes including the essential lpxA, lpxB and dnaE. The possible function of the 17-kDa protein and the other 'actomyosin' components is discussed. PMID- 8354463 TI - Inhibition of adhesion of enteroinvasive pathogens to human intestinal Caco-2 cells by Lactobacillus acidophilus strain LB decreases bacterial invasion. AB - Salmonella typhimurium and enteropathogenic Escherichia coli (EPEC) were found to adhere to the brush border of differentiated human intestinal epithelial Caco-2 cells in culture, whereas Yersinia pseudotuberculosis and Listeria monocytogenes adhered to the periphery of undifferentiated Caco-2 cells. All these enterovirulent strains invaded the Caco-2 cells. Using a heat-killed human Lactobacillus acidophilus (strain LB) which strongly adheres both to undifferentiated and differentiated Caco-2 cells, we have studied inhibition of cell association with and invasion within Caco-2 cells by enterovirulent bacteria. Living and heat-killed Lactobacillus acidophilus strain LB inhibited both cell association and invasion of Caco-2 cells by enterovirulent bacteria in a concentration-dependent manner. The mechanism of inhibition of both adhesion and invasion appears to be due to steric hindrance of human enterocytic pathogen receptors by whole-cell lactobacilli rather than to a specific blockade of receptors. PMID- 8354464 TI - Comparative analysis of three sensitins used in cutaneous testing for tuberculosis and paratuberculosis in cattle. AB - Correspondence between components of sensitins (avian, bovine, and johnin-PPD tuberculins) and the proteins of the corresponding microorganisms (Mycobacterium avium, Mycobacterium bovis and Mycobacterium paratuberculosis) was established. Most of these identified proteins are present in the three organisms, but the 38.3- and 48.8-kDa proteins of M. avium and the 54.0- and 58.7-kDa proteins of M. bovis are endowed with species-specific epitope(s). PMID- 8354465 TI - The in vitro antibacterial activity of ceftriaxone against Streptococcus pyogenes is unrelated to penicillin-binding protein 4. AB - The in vitro activities of penicillin and ceftriaxone were compared against 29 strains of Streptococcus pyogenes with the result that ceftriaxone showed greater activity than penicillin. The morphological changes induced by 1/2 and 1x MIC concentrations of penicillin and ceftriaxone, respectively, were very similar using scanning electron microscopy. Competitive binding studies using 'cold' penicillin or ceftriaxone as inhibitors of radiolabeled penicillin binding demonstrated that ceftriaxone had a very low affinity for penicillin binding protein (PBP) 4 compared to that of penicillin. Since ceftriaxone had greater antibacterial activity, this suggests that PBP 4 may not be important to the in vitro activity of ceftriaxone. In contrast, the IC50 for ceftriaxone was much lower (> 200 fold) for PBPs 2 and 3 compared to PBP 4, suggesting greater avidity of these high molecular mass PBPs for ceftriaxone. These data may at least in part explain the superior in vitro activity of ceftriaxone compared to penicillin against S. pyogenes. These data, together with the observation that PBP 1 was saturated at a lower concentration of penicillin than any of the other PBPs, suggest that the inhibition of PBPs 1, 2, and 3 mediates the bactericidal activity of beta-lactam antibiotics against group A streptococci. PMID- 8354466 TI - Differentiation of Naegleria fowleri and other Naegleriae by polymerase chain reaction and hybridization methods. AB - In order to detect and identify Naegleria fowleri strains an assay based on the Polymerase Chain Reaction (PCR) was evaluated. The amplified DNA fragments were detected by gel electrophoresis and ethidium bromide staining, followed by Southern blot hybridization with an internal digoxigenin-labeled probe. A set of primers (B1B2) which flank a 678-bp region within a virulence-associated gene, allowed for the highly specific identification of N. fowleri, since Naegleriae (N. lovaniensis, N. australiensis, N. gruberi, N. andersoni and N. jadini) and other Protozoa did not react. These primers did not detect amplification products from various organisms: Gram-positive bacteria, Gram-negative bacteria, algae, yeasts and human DNA. Whereas a second set of primers (A1A2), which flank a different sequence, detected various Naegleriae and Acanthamoebae strains. After 40 amplification cycles, the limit of detection was a single cell (cyst or trophozoite). Thus, the PCR appears to be a rapid and powerful tool for identification and detection of N. fowleri. PMID- 8354467 TI - Horizontal spread of an altered penicillin-binding protein 2B gene between Streptococcus pneumoniae and Streptococcus oralis. AB - The region encoding the transpeptidase domain of the penicillin-binding protein 2B (PBP 2B) gene of two penicillin-resistant clinical isolates of Streptococcus oralis was > 99.6% identical in nucleotide sequence to that of a penicillin resistant serotype 6 isolate of Streptococcus pneumoniae. The downstream 849 base pairs of these genes were identical. Analysis of the data indicates that the PBP gene has probably been transferred from S. pneumoniae into S. oralis, rather than vice versa, and shows that one region of this resistance gene has been distributed horizontally both within S. pneumoniae and into two different viridans group streptococci. PMID- 8354468 TI - [The xrs2 gene controls recombination repair in yeast]. AB - The XRS2 mutants of Saccharomyces cerevisiae are sensitive to ionizing and UV irradiation, have altered rates of spontaneous and induced mitotic recombination and are defective in meiosis. Haploid xrs2 cells bearing a mutation in RAD51 or RAD52 genes are more sensitive to gamma-rays than respective single mutants. On the other hand, double mutants xrs2-6 and rad50-1 (cdc40-1, radH) have the same radiosensitivity as the single mutants. At the same time, diploid double mutants xrs2-6rad51 (rad52) have no stronger sensitivity than single rad51 or rad52, whilst xrs2-6cdc40-1 mutant is more sensitive than each of the single mutants. These data confirm our previous assumption that XRS2 gene belong to the RAD52 epistatic group. During vegetative growth of xrs2-6 cells the frequency of plasmid-plasmid recombination as well as plasmid and chromosome copies of ADE2 gene are higher than in wt cells, while the efficiency of recombination during transformation is higher in wt cells but not in xrs2-6 cells. PMID- 8354469 TI - [Fundamental and applied aspects of research on the virus-like plasmids of the yeast Saccharomyces]. AB - Six types of the antagonistic activity (AA) in Saccharomyces were distinguished and characterized. The K1, K2, K3 and K6 activities were associated with the presence of the two kinds of cytoplasmic killer virus-like particles (VLP)- cytoplasmic double-stranded RNAs (dsRNAs) consisting of the main (L) and minor (M) species. All four antagonistic groups contained the L dsRNAs of the same size. The size of the M dsRNAs are dependent on the origin of the host strain. The cytoplasmic inheritance of the K4 activity was observed among the strains which contained no dsRNAs. The AA of this type was not connected with the integrity of mitochondria, also. The K5 activity was under chromosomal control. The optimum and the limits of pH for detection of the AA were dependent on the type of activity. The natural route of extracellular infection by the killer VLPs was the penetration of the VLP into the early protoplast-like spore sprouts. The variability of the K2 activity was studied through mutagenesis of the marked genetic stocks. Twenty six chromosomal genes were involved in the control of this activity. Most of these genetic determinants differed from the chromosomal determinants of the K1 activity in their phenotypes or localization. Four phenotypically different mutational defects of the M-2 plasmid affected the manifestation of the K2 character. Epistatic and cumulative interactions between mutant chromosomal genes controlling the reproduction of the K2 plasmids were observed. Having compared the peculiarities of genetic control of the mutant phenotypes of the K1 and the K2 killers, we acquired the ability to propose a functional model of regulation of the killer virus-like plasmids reproduction. This model defines the interactions between hypothetical gene products and killer dsRNAs or their intermediates. The perspectives of selection of dsRNAs producers were studied. The methods for construction and maintaining the productive strains from the diploids homozygous for a chromosomal mutation increasing the copy number of both K2 killer plasmids were developed. These methods assisted in obtaining the producers suitable for large-scale cultivation. PMID- 8354470 TI - [Role of heat-shock proteins in the recovery of mitotic chromosome damage induced by high temperature in Drosophila melanogaster]. AB - The synthesis of the heat-shock proteins (HSP) and the frequency of the mitotic chromosome damages (pulverizations, chromosome, chromatid stickiness, etc.) was studied in the cells of larva nervous ganglion in the process of recovery after heat shock (37 degrees C, 30 min). Analysis was performed in two strains of Drosophila melanogaster (Canton S-the wild type and the mutant l(1)ts403 with the defect in the HSP system). Correlation between the dynamics of HSP synthesis and the alteration of the chromosome pulverization and stickiness frequency was shown for both Drosophila strains under study. These results, in accord with the data on HSPs' binding to chromosomes following heat shock and their role as molecular chaperones, allowed to suggest that HSPs took part in chromosome condensation and in the recovery of heat shock induced damages leading to chromosome and chromatid stickiness. PMID- 8354471 TI - [An unusual heteromorphic bivalent in the common vole (Microtus arvalis) from Byelarus]. AB - Electron microscopic analysis was carried out on the synaptonemal complexes of ten male common voles (Microtus arvalis) caught of 1990 in Byelorussia. In the early pachytene stage of spermatocytes of four males heteromorphic bivalent has been found in one of five large autosomes. In the central region of the bivalent one of the lateral elements is in the form of a D-loop, characteristic of insertion/deletion heterozygotes. However, high-resolution G-band staining of mitotic chromosomes from fibroblasts showed no significant differences in the G band patterns between homologues. PMID- 8354472 TI - [Immunogenetic similarity and the distance between Swiss brown cattle and 86 other bovine populations]. AB - By using the frequencies of 43-46 antigens of 9-11 genetic blood group systems in 108145 animals the immunogenetic similarity (r +/- m(r)) and the distance (d) between a Swiss brown cattle and other 86 representatives of the Bovinae subfamily were calculated. The position of Swiss brown cattle on a linear model of the Bovinae family was determined. The position has following indexes: r = 0.7816 +/- 0.0197; d = 0.2181. Phylogenesis of 16 cattle breeds reared with participation of the Swiss brown breed was studied. On the dendrogram these breeds formed two clusters and three branches. The clusters at the bottom of the dendrogram (Swiss brown x brown carpathian) and in the middle (ala-tau x caucasian brown) included breeds reared in the foothills and highlands, and the top of the dendrogram is formed by the lebedin, kostroma breeds and the Tajik type of Swiss brown zebu cattle reared in the flat country. PMID- 8354473 TI - [Further analysis of location of the gene for inborn dominant Nochurli cataract]. AB - The study of location of the gene for inborn dominant nokhur kataracta is going on. No linkage of this gene with the locus of alpha-globin gene (16p13.3) and the locus (7q36-qter) was revealed. Additional evidence was obtained for a possible location of the gene for inborn dominant nokhur kataracta on the 14 chromosome. The maximal lod value equaled to 1.089 at theta = 0.20 in the analysis of kataracta genes and alpha-1-antitrypsin (14q32.1), and 0.846 at theta = 0.30 for the kataracta gene and D14S13 (14q32.1-q32.32). For the alpha-1-antitrypsin gene the maximal lod value was 2.24 at theta = 0.05. PMID- 8354474 TI - [Features of the distribution of alleles of the HLA-DRB1 04 and HLA-DQB1 03 genes among healthy people of European origin in Western Siberia]. AB - The allelic HLA-DRB1 04 and HLA-DQB1 03 polymorphism in caucasians living among the West Siberia Mongoloid aborigenes was studied. As a result of our studies, it was shown that the HLA-DRB1 0403/07 predominates and HLA-DRB1 0404/08 is absent in the Russian population of West Siberia, in contrast to those among Caucasians living in West Europe and North America. The frequencies of HLA-DQB1 03 alleles are similar to those observed among the all Caucasians. Gametic association HLA DR4 - HLA-DQw was found for the first time in Caucasians of West Siberia. PMID- 8354475 TI - [Role of individual genes in expression of phenotypic properties of the cold adapted strain A/Leningrad/134/47/57 (H2N2)-a donor of attenuation of live influenza vaccine]. AB - The influenza A/Leningrad/134/47/57 (H2N2) (A/Len/47) cold-adapted virus expresses the ability to reproduce at 25 degrees C (the ca phenotype) and inability to reproduce at 40 degrees C (the ts phenotype). It was attenuated for mice. Reassortants of this donor virus with the genes coding for the surface glycoproteins from the epidemic viruses, i.e. hemagglutinin (HA) and neuraminidase (NA), have been shown to be attenuated, immunogenic and genetically stable. We made attempts to reveal the influence of individual genes from the A/Len/47 ca virus on the expression of some phenotypic properties. Different "single-gene" reassortants were created and investigated using the influenza A/PR/8/34 (H1N1) virus as another parent with the opposite phenotypic properties, i.e. lack of ca+ and ts+ phenotypes and high virulence for mice. We managed to obtain "single-gene" reassortants with PB1, NA and NS genes at this stage of the work. None of them (probably including the M gene as well) could determine the ca or ts phenotypes, nor could the presence of the NA and NS genes from the strain A/Len/47 influence these properties. However, our findings show that the combined influence (synergism) of the PB1 and NS genes from the ca donors results in the ts phenotype of the reassortants. Significant role of the NS gene for attenuation of influenza viruses in mice has been revealed. PMID- 8354476 TI - [A simple and effective method for isolation of DNA from fossil bones for subsequent amplification using the polymerase chain reaction]. AB - A method for DNA extraction from fossil bones based on DNA water elution from the bone powder is proposed. The method allows extraction of paleo-DNA from the great number of bone specimens simultaneously within one day and in quantities sufficient for DNA amplification by the polymerase chain reaction. PMID- 8354477 TI - [Comparative analysis of the level of heterozygosity for glucose phosphate isomerase (GPI) locus in silver foxes (Vulpes vulpes) of domesticated and control populations]. AB - This communication is the first step of the studies on the correlation between protein polymorphism and the level of phenotypic diversity. The level of heterozygosity for glucose phosphate isomerase (GPI) locus was analysed in two populations of silver foxes. One of them has been selected for domestic behaviour during many years. This selection vector gave rise to many phenotypic novelties; 46% of the foxes analyzed has aberrant phenotypes. Another population was control bred under the same conditions of experimental farm of Siberian Dept. Russian Sci. with a commercial purpose. All the foxes analyzed from this population, except one, had a standard phenotype. Among 96 domestic foxes under analysis, only one heterozygotes for the GPI locus was detected. Among 112 control foxes, six were heterozygotes. In other words the data obtained indicate no correlation between the level of morphological diversity and the state of heterozygosity of the GPI locus. PMID- 8354478 TI - [Effect of immobilization of amidopyrine in polyvinyl alcohol on mutagenicity of yeast]. AB - Frequency of gene mutations was studied on the yeast Saccharomyces cerevisiae after treatment with amidopyrine (AP) and polyvinyl alcohol (PVA). PVA was found to have no mutagenic activity, whereas AP increased mutation frequency in dependence of drug concentrations (15 and 30 mg/ml) and the duration of cell treatment (4 and 24 hours). Immobilization of AP in PVA led to decrease in drug mutagenicity. PMID- 8354479 TI - Prevention of atopic diseases in high risk babies (long-term follow-up). AB - Several studies have demonstrated that dietary and environmental manipulations in the first months of life have a protective effect on the development of allergic diseases in babies "at risk" of atopy. We have prospectively followed up 174 "high risk" infants who underwent dietary and environmental manipulations, such as exclusive breast-feeding for the first 6 months of life, supplemented if necessary with soy-protein formula (Isomil, Abbott), delayed weaning beyond the 6th month of life, and rigorous environmental manipulations for the elimination of house-dust mite and passive smoking. The low prevalence of atopic disease (10%) and the trivial course of the allergic manifestations in this "at risk" population confirm the effectiveness of this preventive program. Moreover, this study demonstrates that the incidence of atopic dermatitis peaks at 6 months, and decreases until it disappears. Food allergy appears only at 6 months and may disappear later. The incidence of asthma peaks at 6 and 36 months and decreases at low levels in the intervals. Allergic rhinitis develops not sooner than 36 months. PMID- 8354480 TI - Murine monoclonal antibodies to glycoprotein antigens of Aspergillus fumigatus show cross-reactivity with other fungi. AB - Six monoclonal antibodies produced against Aspergillus fumigatus were studied for their cross-reactivity against other fungal antigens from related and unrelated organisms. Five of the monoclonal antibodies reacted with glycoprotein antigens as evidenced by their binding to concanavalin A, although one did not react with concanavalin A. The reactivities of the monoclonal antibodies with various antigens were studied by biotin-avidin linked immunosorbent assay and Western blots. The results indicate that two monoclonal antibodies (Asp D1 and Asp C9) react with antigens from aspergilli as well as other fungi including Penicillium notatum and Candida albicans, whereas three of six antibodies (Asp H10, Asp ILB8, and Asp C2B1) react with A. fumigatus antigen only. Hence, these monoclonal antibodies can be used to obtain group specific and species specific antigens for various immunodiagnostic assays. PMID- 8354481 TI - Polymerization and fractionation of house dust mite allergen. AB - Glutaraldehyde polymerization and appropriate fractionation of allergens result in significantly decreased allergenicity with retained immunogenicity. In a manner similar to that employed with other allergens, we have prepared monomer dust mite (MDM) and polymerized dust mite (PDM). As with other polymerized allergens such as polymerized ragweed, PDM is more than 2 logs less allergenic than MDM as determined by cutaneous end point titration in sensitive patients. Moreover, PDM and MDM are similarly immunogenic in rabbits. As determined by inhibition studies (with rabbit antisera) PDM is antigenically complete and contains no new epitopes against which antibody was produced. In summary, we have prepared PDM which has the desired characteristics of reduced allergenicity, retained immunogenicity, antigenic completeness, and absence of new antigenic determinants. PMID- 8354482 TI - Standardization of allergenic extracts: a manufacturer's perspective. AB - The current procedure for standardizing allergenic extracts utilizes quantitative skin testing techniques and in vitro techniques. A reference preparation is selected and tested using a sensitive intradermal skin test technique to determine allergy units. Subsequent batches of standardized extracts are compared to the reference preparation using in vitro techniques. The standardization program has accelerated over the past few years and all indications are that it will continue to do so in the future. PMID- 8354483 TI - Portugal's contribution to navigation and discovery of the New World. AB - Even before the birth of Prince Henry the Navigator (1394) Portugal had displayed a maritime calling due to its 500-mile shore line and numerous natural bays. Inspired by the riches of India he saw during the Portuguese exploration along the coast of West Africa, Prince Henry set out methodically to collect information by bringing together Jews and Moors with geographical knowledge to found his School of Navigation. From 1415 until his death in 1460 he attracted to his school the foremost contemporary scholars in mathematics, astronomy, and cartography along with experts in knowledge of the compass, astrolabe, water currents, and the winds. This concentration of talent yielded the invention of the caravel, the most important navigational advancement of the time, crucial for long voyages across the high seas. Although the rest of Europe busied itself in political and religious wars, for 70 years (1415-1492) Portugal alone pursued the discovery of the Atlantic. "No nation in the 15th century exhibited so great a spirit of maritime enterprise as the Portuguese." PMID- 8354484 TI - Art and artifice in the science of histology. 1933. AB - Introduction to the original article. Dr Pio del Rio-Hortega has been working 'temporarily' in a little laboratory in La Residencia for the past 15 years. With exemplary perseverance and goodwill, he has carried out, in this little corner, a labour that has been greatly appreciated by researchers throughout the world, but is perhaps not sufficiently recognized among ourselves. Through the use of original methods he has been able to make visible the most delicate details of the structure of cells. His research on the histology of the nervous system led him to discover a new species of cells, which the scientific world has baptized, in his honour, with the name of 'Hortega cells'. His uninterrupted line of investigation continues with research on tumours of the nervous system, on which he was confirmed as the leading authority at the last International Conference on Cancer. Dr Rio-Hortega is a devotee of the visual arts, and a fruit of the marriage between his enthusiasm for art and his scientific activities is the article that follows. PMID- 8354485 TI - Chromogranin A, secretogranin II and vasoactive intestinal peptide in phaeochromocytomas and ganglioneuromas. AB - By means of immunohistochemistry we analysed the distribution of chromogranin A, secretogranin II and vasoactive intestinal peptide (VIP) in 16 phaeochromocytomas, two cases of combined phaeochromocytoma-ganglioneuroma and four adrenal ganglioneuromas. Chromogranin A was found in the majority of phaeochromocytes and in mixed phaeochromocytomas-ganglioneuromas. Secretogranin II was present to a lesser degree in phaeochromocytes, but strong immunostaining was found in most ganglion cells of phaeochromocytomas, in the ganglioneuroma component of combined tumours and in adrenal ganglioneuromas. Vasoactive intestinal peptide was present in some ganglion cells of phaeochromocytomas, in the ganglioneuroma component of mixed tumours and in three of four adrenal ganglioneuromas. On semi-adjacent sections a co-localization of VIP and secretogranin II was demonstrated. These results indicate that neuronal differentiation is accompanied by an increased immunohistochemical expression of secretogranin II. Therefore, secretogranin II may be a useful marker for ganglion cell differentiation. PMID- 8354487 TI - The value of histomorphological features of chorionic villi in early spontaneous abortion for the prediction of karyotype. AB - This study was conducted to evaluate the value of histomorphological features of chorionic villi, such as size, shape, vascularity, trophoblast proliferation and trophoblastic pseudo-inclusions, for the prediction of chromosomal abnormality. Slides of 83 early spontaneous abortions were assessed by three observers. Assessments and karyotype were compared and likelihood ratios computed. Likelihood ratios of < or = 0.40 or > or = 2.50 were not obtained by all three observers for any of the features. One or two observers obtained likelihood ratios of > or = 2.50 for lacunar stromal hydrops, presence of trophoblastic hyperplasia, moderate to abundant trophoblastic hyperplasia, presence of trophoblastic lacunae, few intervillous fibrin deposits and few intervillous trophoblastic buds. Likelihood ratios of < or = 0.40 were found for small chorionic villi and presence of basophilic staining. Lacunar stromal hydrops and trophoblastic lacunae were predictive of triploid karyotype, but not specific for any other type of chromosomal abnormality. After application of data previously obtained on Cohen kappas, lacunar stromal hydrops, moderate to abundant trophoblastic hyperplasia and presence of trophoblastic lacunae remained as possibly useful features, again mainly for identifying triploidy. Most of the items claimed to be related to abnormal karyotype, however, were not predictive at all. PMID- 8354486 TI - Immunohistochemical characteristics of Hodgkin and Reed-Sternberg cells in relation to age and clinical outcome. AB - One hundred and fifty-four cases of Hodgkin's disease diagnosed between 1985 and 1988 from an unselected population were stained with a panel of six monoclonal antibodies; LN1, MB2, L26 (CD20), all B-cell antibodies, UCHL1 (CD45 RO), mainly T-cell antibody, Leu M1 (CD15), Ber H2 (CD30) and the polyclonal CD3, T-cell antibody. The results were related to age, histopathological subgroup and prognosis. There was no significant difference in staining patterns in the 90 patients below the age of 60 compared with the 54 patients above that age. In the entire group, significantly fewer mixed cellularity cases were positive with Ber H2 and Leu M1 compared to nodular sclerosis. Disease-free survival tended to be better for cases stained with T-cell related antibodies. This study thus indicated differences in behaviour between T-cell positive and negative Hodgkin's disease and that there are antigenic differences between nodular sclerosis and mixed cellularity subgroups. We could not, however, show any phenotypic differences between the tumour cells in young and old patients. PMID- 8354488 TI - Pustular drug eruptions: a histopathological spectrum. AB - We have reviewed the histopathological features of 11 patients with pustular drug eruptions. Two main histological patterns were seen. Eight cases revealed features of toxic pustuloderma with the presence of spongiform intraepidermal pustules in association with papillary oedema and a mixed inflammatory cell infiltrate around upper dermal blood vessels. Pustules were present at different levels within the epidermis. The other three cases exhibited leucocytoclastic vasculitis with neutrophil collections both below and within the epidermis. One case showed continuity between the subepidermal and intra-epidermal pustules. These findings suggest a dynamic process in which neutrophils collect around upper dermal blood vessels and are then eliminated via the overyling epidermis. The presence of extravasated red blood cells within the intra-epidermal pustules indicates that this process is passive rather than the result of specific chemotaxis or cell migration. PMID- 8354489 TI - Benign trichogenic tumours: a report of two cases supporting a simplified nomenclature. AB - We report two cases of a rare benign tumour of hair germ. Clinically, both were solitary, well-circumscribed, subcutaneous nodules located in the extremities. Histologically, the tumours were characterized by nests and thin cords of basaloid epithelial cells intimately associated with a cellular stroma. The basaloid cells exhibited peripheral palisading, keratinization in the form of keratotic cysts and squamoid transformation, and pilar differentiation. An unusual, but distinctive, cribriform pattern of growth was observed. There was no communication with the overlying epidermis. Abundant primitive hair germinal buds and rare more advanced abortive hair follicles were identified. These histological appearances encompass features of both trichoblastic fibroma and trichogenic trichoblastoma, thus distinguishing these neoplasms from other skin tumours and reinforcing the hypothesis that these tumours are closely related from a histogenetic point of view. The presence of overlapping histological features can be problematic for practising histopathologists who rarely encounter these conditions. With this in mind, the term benign trichogenic tumour may be more appropriate to encompass these two tumours and related neoplasms that appear to lie within the spectrum of hair follicle development. PMID- 8354490 TI - The value and significance of nucleolar organizer region (AgNOR) proteins in ulcerative colitis and adenocarcinomas of the large bowel. PMID- 8354491 TI - Rectal biopsy as a diagnostic procedure of chronic visceral leishmaniasis. PMID- 8354493 TI - Partial nodular transformation of liver in a child. PMID- 8354492 TI - Pigmented ganglioneuroblastoma: a tumour cell 'storage disease'? PMID- 8354494 TI - Histological classification of tissue from spontaneous abortions: a valueless exercise? PMID- 8354495 TI - Leiomyoid mesotheliomas. PMID- 8354496 TI - Hepatic angiomyolipomas. PMID- 8354497 TI - Hispanic, Latino, or Raza? Coming to terms with diversity. PMID- 8354498 TI - Civil liability of mentally ill persons. PMID- 8354499 TI - Using field trials to evaluate proposed changes in DSM diagnostic criteria. PMID- 8354500 TI - Developmental psychoacoustics: what infants and children hear. PMID- 8354501 TI - The agitated patient, Part II: Pharmacologic treatment. PMID- 8354502 TI - Chronic depression. AB - OBJECTIVE: Chronic depression has not been appreciated or studied as well as episodic mood disorders or other chronic psychiatric disorders. This review provides an overview of the clinical features, biology, and treatment of chronic depression and suggests additional areas for research. METHODS: The English language literature was searched using MEDLINE. Additional references were selected from the bibliographies of recent publications. Studies of chronic nonbipolar depressed patients were selected; chronicity was defined as the persistence of depressive symptoms for at least two years or as a diagnosis of DSM-III or DSM-III-R dysthymia, "double depression," or chronic major depression. RESULTS AND CONCLUSIONS: Reported prevalence rates of chronic depression range from 3 to 5 percent in community samples and from 9 to 31 percent in clinical samples. Compared with patients with major depression, those with chronic depression have increased neurotic personality traits, adverse life events, health care utilization, and comorbid psychiatric and medical conditions, especially thyroid dysfunction. Biological and family studies support the relationship of chronic depression to the major mood disorders. Chronicity is also associated with inadequate treatment with anti-depressant drugs. Serotonergic or monoamine oxidase inhibitors may be more effective in treating chronic depression than tricyclic antidepressants. Psychosocial therapies need further study but may be especially useful in combination with drug treatment. Future research should investigate the clinical and biological correlates of subtypes of chronic depression, the response of the subtypes to different antidepressants, and the relative efficacy of combined antidepressant psychosocial treatment. PMID- 8354503 TI - Outcomes for the mentally ill in a program for older homeless persons. AB - OBJECTIVE: The study evaluated the success of a generic service program for older homeless persons in improving the well-being of mentally ill clients. It attempted to identify factors that predicted the number of service encounters and outcome in seven areas, including housing, entitlements, physical and mental health, and sobriety. METHODS: All persons newly admitted to the program during a two-and-a-half-year period were asked to participate in structured interviews assessing their physical and mental health and their support networks. Two-thirds of those eligible, or 130, participated in the intake interviews. At three-year follow-up or last contact, outcome was compared for 41 psychiatric clients with psychotic symptoms or self-reported history of psychiatric hospitalizations and 89 clients with no psychiatric symptoms or previous hospitalizations. RESULTS: Persons with mental illness averaged 2.5 favorable outcomes, and a majority obtained temporary or permanent housing, improved their physical health, and secured entitlements. However, mentally ill clients had significantly fewer service encounters and favorable outcomes than clients who were not mentally ill. Types of presenting problems at intake were the only significant predictors of outcome for mentally ill clients. CONCLUSIONS: A generic service program for older homeless persons can successfully improve the well-being of mentally ill clients, although outcomes are less favorable for such clients than for clients who are not mentally ill. PMID- 8354504 TI - Characteristics of children whose parents have been incarcerated. AB - OBJECTIVE: The study sought to determine the relationship between parental incarceration and behavioral and family characteristics among children in a day hospital. METHODS: Chi square analysis and t tests were used to compare preadmission characteristics and teachers' behavioral ratings of a group of 16 children in a day hospital setting who had experienced the incarceration of one or both parents and a group of 21 children in that setting who had no history of parental incarceration. RESULTS: Children in the parental incarceration group were significantly more likely to have experienced parental substance abuse than those whose parents had not been incarcerated. A history of child abuse or maltreatment appeared to be more likely among the parental incarceration group. Boys whose fathers had been incarcerated received higher teacher ratings of delinquent and aggressive behavior. Paternal incarceration among girls was associated with a significant increase in attention problems. CONCLUSIONS: A history of parental incarceration may be quite common in some mental health samples of children. It appears to be associated with severe family dysfunction and behavioral disorders. PMID- 8354505 TI - The boundaries of psychiatric rehabilitation. AB - The authors describe the development of modern psychiatric rehabilitation, from its early association with occupational therapy to its present state as a discipline with an armamentarium of treatment strategies. Psychiatric rehabilitation addresses difficulties in three domains of patients' lives: clinical status, functional status, and quality of life. The authors suggest that the acceptance of rehabilitation as a separate discipline has been slow due to boundary conflicts between these domains and between the disciplines that traditionally represent them. The authors call for a more central role for rehabilitation, which integrates treatment in the three domains and uses group methods to formulate plans and enhance client involvement. PMID- 8354507 TI - Development and evaluation of drop-in centers operated by mental health consumers. AB - As part of a statewide initiative begun in 1989 to promote consumer involvement, the Pennsylvania Office of Mental Health initially funded the development of nine consumer-operated drop-in centers. This paper describes some of the programs and services developed by the centers and presents results of a survey of consumers' use of and satisfaction with services. During the six-month survey period, a total of 478 consumers used services; average daily attendance at each center was 28. Most centers had one paid position supplemented by heavy use of volunteers. Most projects had collaborative relationships with a few providers who maintained a low profile in daily operations. Although consumers were highly satisfied with the drop-in centers, they desired improvements in the number of paid staff, hours of operation, management, and transportation. PMID- 8354506 TI - Respecting the autonomy of chronic mentally ill women in decisions about contraception. AB - Treatment of women patients with chronic mental illness who are at risk of unwanted pregnancies presents ethical challenges to the clinician who wishes to respect the patient's autonomy while also helping her avert the potential adverse consequences of unwanted pregnancy. The clinician who simply allows the patient to continue at risk or coerces her into using contraception may not have adequately considered the variable nature of the patient's autonomy. The authors suggest that the clinician should assess and treat conditions underlying the patient's variable impairment of autonomy to maximize her ability to participate in family planning decisions. Case examples are used to illustrate assessment of patients' decision-making capacity, development of family planning approaches that respect patients' autonomy, and use of a newly available contraceptive implant. PMID- 8354509 TI - What employers want in managed care programs. PMID- 8354508 TI - Psychoeducation in Spain. PMID- 8354510 TI - Pay as an incentive in work participation by patients with severe mental illness. PMID- 8354511 TI - Esophageal atony and dilatation as a side effect of thiothixene and benztropine. PMID- 8354512 TI - Race and therapeutic alliance. PMID- 8354513 TI - Medicaid in state hospitals. PMID- 8354514 TI - Drug-induced mania. PMID- 8354515 TI - Drug use by day patients. PMID- 8354516 TI - Hospitalphilia. PMID- 8354517 TI - Ternary complex formation with 5-fluoro-2'-deoxyuridylate and the kinetic properties of thymidylate synthase from Lactobacillus leichmannii. AB - Lactobacillus leichmannii thymidylate synthase (5,10-CH2-H4PteGlu:dUMP C methyltransferase, EC 2.1.1.45) forms a tight and stable covalently bonded ternary complex with the inhibitor 5-FdUMP in the presence of the cofactor 5,10 CH2-H4-PteGlu. 'Filter assay' employing the radioactive nucleotide ligand showed that 2 moles of FdUMP are bound per mole enzyme during the ternary complex formation with the L. leichmannii dTMP synthase. This is in line with our earlier observation on the Streptococcus faecium thymidylate synthase [Narasimha Rao, K & Kisliuk R L (1983), Proc Natl Acad Sci USA, 80, 916-920]. The enzyme has Km values of 6.3 x 10(-6) M, 8.2 x 10(-5) M and 1.0 x 10(-4) M for dUMP, (dl)-L H4PteGlu and Mg2+ respectively; Vmax for dUMP, (dl)-L-H4PteGlu and Mg2+ are; 0.55, 0.5 and 1.1 respectively. It has K(i) values of 6.7 x 10(-6) M, 2.2 x 10( 6) M, 5.0 x 10(-5) M and 2.0 x 10(-4) M for FdUMP, dTMP, MTX and Ca2+ respectively. The type of enzyme inhibition with FdUMP, dTMP, MTX and Ca2+ was competitive. dTMP Studies clearly show the 'end product' inhibition of the enzyme. PMID- 8354518 TI - Sugar-specific interaction of bovine brain beta-galactoside-binding lectin with endogenous gangliosides. AB - Sugar-specific binding of the 14 kDa beta-galactoside-binding lectin from bovine brain grey matter to mixed endogenous gangliosides was demonstrated by affinity electrophoresis and hemagglutination inhibition. Gangliosides prepared by Folch extraction, base treatment and silica gel chromatography, when incorporated in native or desialated form in polyacrylamide gel above their critical micellar concentration, arrested the mobility of the lectin during electrophoresis at pH 8.2. This effect was sugar-specific since it was reversed if lactose, but not sucrose, was present in the gel. Also, retention of the brain lectin by ganglioside and its reversal by lactose were concentration-dependent. In presence of bovine serum albumin, at pH 7.4 native and desialylated gangliosides equally inhibited agglutination of trypsinized rabbit red cells by bovine brain lectin, but not that by the alpha-galactoside-specific antibody from human serum. Results suggested the possibility of endogenous gangliosides acting as cell surface receptors in mediation of brain lectin function. PMID- 8354519 TI - Biochemical activities of denatured covalently closed circular duplex DNA. AB - Covalently closed circular duplex DNA when exposed to high alkaline pH followed by neutralization yields a collapsed state structure (form I(d)) that can undergo transition to form I and was susceptible to S1 nuclease. Form I(d), in spite of its compact structure, admits specific cleavage by restriction enzymes over its entire genome. When used in a semi-in vitro replication complex, form I(d) gave significantly better template activity, and undergoes better primer extension in in vitro using Klenow. Thus form I(d) having a compact shape can behave as a better substrate in a few key enzymatic reactions. PMID- 8354520 TI - Effect of propranolol hydrochloride on blood cell lipids in relation to partition coefficient and biological activity. AB - Considering the high lipophilicity of propranolol (log P = 3.56), its interactions with the cell membrane lipids of goat blood have been investigated. It is observed that lipid loss after incubation of blood cells with propranolol hydrochloride in salt glucose medium for varying periods of time was accompanied with significant increases in PUFAs. Amongst the PUFAs studied the omega 3 and omega 6 fatty acids, the two important precursors of eicosenoids, have shown increase in varying amounts. This phenomenon is presumably responsible for the significant cardiovascular activity of this drug. PMID- 8354521 TI - Telomere structure and function. PMID- 8354522 TI - Effect of substrate and phosphate ions on the quaternary structure symmetry of glyceraldehyde-3-phosphate dehydrogenases of mung beans and rabbit muscle. AB - Effects of glyceraldehyde-3-phosphate (G-3-P) and phosphate ions on thermal inactivation of glyceraldehyde-3-phosphate dehydrogenases (GPDHs) of mung beans and rabbit muscle have been studied at different pH. In the absence of any ligand, the two enzymes show a striking similarity in the pH-dependence of the kinetics of thermal inactivation. At lower pH values both the enzymes biphasic kinetics with each phase accounting for about half of the starting activity (a C2 symmetry of the homotetrameric enzyme molecule). The kinetics change to a single exponential decay at higher pH values, a D2 symmetry [Malhotra & Srinivasan (1985) Arch. Biochem. Biphys. 236, 775-781; Malhotra & Tikoo (1991) Indian, J. Biochem. Biophys. 28, 16-21]. With each enzyme, phosphate ions are found to have no effect on the kinetic pattern at lower pH, but G-3-P brings about a change from biphasic to a single exponential decay. At higher pH values, G-3-P has no effect on the single exponential decay kinetic pattern, but phosphate ions change the same to a biphasic loss of activity with each phase accounting for about half of the starting activity. It has been concluded that with both the enzymes, G-3-P and phosphate ions have higher affinity and stabilise the D2- and C2-symmetry conformation, respectively. Binding isotherms of the two substrates for these enzymes have been described based on the ligand concentration-dependence of the changes in the rate constants and kinetic pattern of thermal inactivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354523 TI - Studies on cinnamic acid-4-hydroxylase from wounded potato tissue: isolation and characterization of cinnamic acid-4-hydroxylase activation factor. AB - Cinnamic acid-4-hydroxylase activation factor has been found to be located in the supernatant fraction of wounded potato tissue homogenate in phosphate buffer. The factor has been purified to homogeneity as judged by SDS polyacrylamide gel electrophoresis, by heat treatment on boiling water-bath for 7.5 min followed by dialysis with cut off limit of 8 kDa and final separation by gel filtration on Sephadex G-50 column. Gel filtration resolved this into three active fractions of molecular mass 12500, 10000 and 8500 Da conjugated to a fluorescent compound and subsequently identified as a folate derivative. The amino acid analysis of polypeptide chains of these fractions revealed that the polypeptides were rich in glutamic and aspartic acids. The fluorescent moiety of the complex released from polypeptide chain of molecular weight 10000 by mild acid hydrolysis was able to support the growth of Lactobacillus casei ATCC 7469 which requires folic acid for its growth. On storage, this compound degraded into a number of fluorescent products identified as p-amino benzoic acid, p-amino benzoyl glutamic acid, pteroic acid and 6-methyl pterin indicating that the activation factor is a folic acid derivative conjugated with the polypeptide chain. PMID- 8354524 TI - Ca(2+)-induced alterations in the activity of membrane (Ca(2+)-Mg2+)-ATPase of human and rat erythrocytes. AB - Effect of intraerythrocyte Ca2+ elevation on human and rat erythrocyte membrane (Ca(2+)-Mg2+)-ATPase along with that of incubation of the erythrocyte ghosts in their own hemolysates enriched with Ca2+ has been studied. While the membrane (Ca(2+)-Mg2+)-ATPase levels of Ca(2+)-loaded human erythrocytes showed an initial increase and subsequent decline, membranes incubated in their own hemolysate showed a consistent decrease in the enzyme activity. Calmodulin sensitivity was retained by the preparations in contrast to the earlier observations made with washed erythrocyte membranes. Similar changes in (Ca(2+)-Mg2+)-ATPase activity but of greater magnitude were observed in response to Ca2+ in the calpain-rich rat erythrocytes. Considerable crosslinking and proteolysis was observed in case of human and rat erythrocytes exposed to high Ca2+ concentrations. The Ca(2+) activable transglutaminase, however, did not play any role in the activation of the (Ca(2+)-Mg2+)-ATPase. PMID- 8354525 TI - Halothane-induced fulminant hepatic failure. AB - Fulminant hepatic failure developed in the early post-operative period in a patient after third exposure to halothane. Exclusion of other causes of post operative jaundice and temporal relationship of jaundice to anesthesia suggested halothane as the etiologic agent for the submassive necrosis, which was documented at postmortem liver biopsy. PMID- 8354526 TI - Volvulus of stomach in childhood. AB - Six children, aged upto one year, with volvulus of the stomach are reported. Vomiting and regurgitation of feeds were the main presenting symptoms. Eventration of the left hemidiaphragm was present in four cases. Barium meal confirmed the diagnosis. Five cases were operated on through an abdominal approach. Plication of the diaphragm (3 cases), colonic displacement (2) and gastrostomy (3) were resorted to. One child needed reoperation for a missed Ladd's band. There was no operative mortality. PMID- 8354527 TI - Splenic hemangiomatosis with osseous involvement. AB - A rare case of splenic hemangiomatosis with bone involvement in the upper extremity is presented. The findings on ultrasonography and CT scan abdomen were suggestive of splenic hemangiomatosis. X-ray of left forearm showed findings characteristic of osseous hemangiomatosis, which was subsequently confirmed on histology. PMID- 8354528 TI - The case of a sticky stomach. PMID- 8354529 TI - Percutaneous endoscopic gastrostomy in patients with head injury. PMID- 8354530 TI - Newer stool based diagnostic tests in infectious diseases: possibilities and pitfalls. PMID- 8354531 TI - Perforated duodenal ulcer: is definitive surgery warranted? PMID- 8354532 TI - Detection of Entamoeba histolytica antigens in stool in amebiasis. AB - BACKGROUND: Stool microscopy, the conventional method of diagnosing intestinal amebiasis, fails to detect Entamoeba histolytica in more than 30-40% of clinically suspected cases. Demonstration of parasite products in clinical specimens has been suggested as an alternative. However, the usefulness of demonstrating amebic antigen in the stools of clinical cases needs to be assessed. METHODS: A double-antibody sandwich enzyme linked immunosorbent assay (ELISA) using anti-trophozoite antibodies to capture E histolytica specific coproantigen(s) was carried out on stools obtained from 31 patients with microscopically confirmed non-dysenteric amebic colitis, 18 patients with intestinal parasites other than E histolytica and 41 apparently healthy subjects. RESULTS: The assay detected E histolytica specific coproantigen(s) in stools of 23 (74.2%) of 31 subjects with non-dysenteric amebic colitis, none of 18 with other parasitic infections and 1 (2.4%) of 41 apparently healthy subjects. CONCLUSION: Our results provide evidence for the presence of E histolytica specific coproantigen(s) in stool eluates from patients with amebic infection; this finding can be exploited for confirming ongoing amebic infection. However, the sensitivity of the assay needs to be improved by the use of relevant monospecific/monoclonal antibodies. PMID- 8354533 TI - Is ulcer recurrence after simple closure of perforated duodenal ulcer predictable? AB - OBJECTIVE: To study whether factors such as age, duration of pre-perforation symptoms, size of perforation and operative evidence of chronicity could predict recurrence of ulcer after simple closure of perforated duodenal ulcers, thus enabling patients at high risk of recurrence to be subjected to definitive surgery instead of simple closure of perforation. DESIGN: Retrospective. One hundred and fifty-two patients who had undergone simple closure of duodenal ulcer perforation in the last 10 years were included in the study. SETTING: A postgraduate research and teaching institution. PATIENTS AND MEASUREMENTS: Patients were subjected to a personal interview and Visick grading of symptoms 1 10 years after simple closure of duodenal ulcer perforation. Ninety of them underwent esophagogastroduodenoscopic evaluation. RESULTS: Symptomatic ulcer recurrence rate was 23.1% by Visick grading and 42.2% on endoscopy. Ulcer symptom recurrence rate had no correlation with patient's age, duration of pre perforation symptoms, or size of perforation, but correlated significantly with operative evidence of chronicity (p < 0.001). However, 7 of 35 symptomatic recurrences would have been missed by the use of this criterion alone. Endoscopic evidence of recurrence also correlated only with operative evidence of chronicity. False positives and false negatives with Visick grading showed that this symptomatic evaluation was unsatisfactory even for selecting patients for further endoscopic workup. CONCLUSION: Though not infallible, evidence of chronicity of ulcer at laparotomy may be a useful predictor of recurrence of ulcer after simple closure of perforated duodenal ulcer. PMID- 8354535 TI - Role of anxiety and personality in non-ulcer dyspepsia: a comparative study with duodenal ulcer. AB - BACKGROUND: Though emotional factors are known to influence gut functions, studies evaluating the role of anxiety and personality in non-ulcer dyspepsia (NUD) are few and have not yielded consistent results. AIMS: To find out whether anxiety and abnormal personality pattern are specifically associated with NUD. METHODS: 33 patients with NUD and 30 patients with duodenal ulcer, who were randomly selected from among those attending a gastroenterology out-patient clinic, were administered a) the Eyesenck Personality Inventory, to measure neuroticism and extroversion; and b) a short self-rating scale for anxiety, to measure state and trait anxiety. RESULTS: There were no significant differences between the two groups in state anxiety, neuroticism and extroversion. Trait anxiety, however, was significantly higher in the NUD group (p = 0.05). CONCLUSIONS: Though the difference in trait anxiety score between the two groups attained significance, this finding needs further support to indicate a causal role for anxiety in NUD. There is need for further studies about the role of anxiety in various subgroups of NUD. PMID- 8354534 TI - End point for sclerosis of esophageal varices. AB - BACKGROUND: Small esophageal varices are difficult to inject intravariceally and complete eradication of varices may not be therapeutically necessary. METHODS: A prospective study designed to compare the use of different end points of sclerotherapy ie (i) total eradication (grade 0) (ii) grade I varices or (iii) grade II white (IIw) varices, by stopping variceal injection when one of these was reached. The patients were followed endoscopically and clinically at 3-4 mo intervals. OUTCOME MEASURES: Variceal recurrence and rebleeding rates. RESULTS: Of 266 patients with portal hypertension (147 cirrhosis, 51 non-cirrhotic portal fibrosis, 68 extra-hepatic portal venous obstruction), 232 (87.2%) reached one of the three end points--six to grade 0, 96 to grade I and 130 to grade IIw. Among 212 patients followed up for a mean post-sclerotherapy period of 12.2 mo (range 3 48 mo), variceal recurrence rates, time intervals to recurrence and rebleed rates were comparable in patients with endpoints of grade I and grade II (white) varices (28.5% vs 38.9%, 10.8 mo vs 9.2 mo, and 7.7% vs 7.8%, respectively; all p = ns). Overall, 51 patients had interval bleed before reaching the end point--50 (98%) of them bled from grade III and IV varices while only one patient (2%) bled with grade IIw varices. CONCLUSION: Grade I or grade IIw varices should be acceptable as the end points for endoscopic sclerotherapy of esophageal varices. PMID- 8354536 TI - Combination of anticholinergic agent and H2 receptor antagonist in duodenal ulcer treatment--a randomized, double blind multicenter study. AB - BACKGROUND: The acid suppressive abilities of H2 receptor antagonists and anticholinergics have been claimed to be additive. METHODS: A multicenter, double blind, randomized trial comparing ranitidine (150 mg) plus propantheline bromide 15 mg at bedtime to ranitidine 300 mg alone at bedtime was conducted in 161 patients with endoscopically confirmed uncomplicated duodenal ulcer. RESULTS: After six weeks of therapy, ulcer healing rates in the two groups were comparable ie 80% in the combination group (ranitidine + propantheline) and 79.4% in the ranitidine group. Pain relief after one, two and four weeks of treatment was also comparable in the two groups. Side effects to drugs were minor and comparable in both the groups. CONCLUSION: A combination of 150 mg ranitidine and 15 mg propantheline bromide is as efficacious as 300 mg ranitidine in inducing healing of uncomplicated duodenal ulcers, with similar side-effects but at greatly reduced cost. PMID- 8354537 TI - Involvement of prostaglandins in chilli-induced early gastric vascular damage in adult Wistar rat. AB - OBJECTIVE: To explore the role of prostaglandins in protecting against chilli induced early gastric vascular damage. METHODS: Early gastric vascular damage was induced in rats by oral administration of 8 mg/Kg chilli extract. The damage was assessed by estimating spectrophotometrically the amount of Evan's blue leaking into gastric tissue and luminal contents 10 min after exposure to chilli. Further groups of rats were pretreated with misoprostol (10, 25 or 50 micrograms/Kg) or dazmegrel (1, 5 or 25 mg) to evaluate their protective effects. RESULTS: Both misoprostol and dazmegrel were able to reduce gastric vascular damage induced by chilli in a dose-dependent fashion. CONCLUSION: Prostaglandins may play a role in protecting against chilli-induced early gastric vascular damage. PMID- 8354538 TI - Retraction of publication. PMID- 8354539 TI - Endoscopic variceal ligation: an effective method of variceal obliteration. AB - Endoscopic variceal ligation was performed in 20 patients with portal hypertension of varied etiology. Variceal obliteration was achieved in 18 patients (90%) while recurrence of bleeding occurred in two patients (10%). The average number of bands required was four per patient and average number of sessions required for variceal obliteration was two. We found the procedure to be cheap, safe and effective in achieving early variceal obliteration. PMID- 8354540 TI - Emergency endoscopic nasobiliary drainage without the aid of fluoroscopy. AB - Endoscopic nasobiliary drainage without the aid of fluoroscopy, as an emergency procedure, was performed successfully in four patients with severe calculous cholangitis. There were no complications. All the patients improved and three were taken for definitive surgery later. PMID- 8354541 TI - Hyperbilirubinemia following hepatitis A in a patient with G6pD deficiency. AB - A case of viral hepatitis A with G6PD deficiency is described. The condition should be suspected in the presence of indirect hyperbilirubinemia, and anemia in a patient with viral hepatitis; repeat G6PD testing 8 weeks later is recommended for diagnosis. PMID- 8354542 TI - Modifications in the seminal protein pattern and concentration among infertile men. AB - Lower concentrations of protein observed in semen of infertile men were mostly due to absence of vesicular proteins with higher isoelectric pH above pH 8.3. Two to four proteins with lower isoelectric pH showing electrophoretic mobility and originating both from seminal vesicle and prostate were absent in infertile semen samples. Concentrations of such proteins among oligozoospermic and azoospermic samples with complete maturation arrest and Sertoli cell only syndrome decreased mainly towards cathode, whereas, in vasectomized azoospermia the number of protein bands decreased both towards cathode and anode, though the concentration decreased mainly in the anodic proteins. PMID- 8354543 TI - Environmental conditions, anthropometric parameters and arterial blood pressure. AB - The influence of environmental conditions and anthropometric parameters on arterial blood pressure level was studied in 280 healthy Kashmiri subjects, aged 18-50 years (140 males, 140 females) Men in the age group of 18-20 years had higher blood pressure than women and their systolic blood pressure showed significant correlation with height, weight and skinfold thickness. Females (18 20 years) showed association of diastolic blood pressure with weight, skinfold thickness. Females (18-20) years) showed association of diastolic blood pressure with weight, skinfold thickness and mid-arm circumference. After the age of 20 years females had higher blood pressure than males. Height and weight decreased with age in both the sexes. Skinfold thickness and midarm circumference increased with age in females. A comparison between the present study and those reported from Haryana and Delhi revealed a higher diastolic pressure in Kashmiris. PMID- 8354544 TI - Purulent pericarditis caused by Salmonella typhimurium--a case report. PMID- 8354545 TI - Immunological tests for diagnosis of tuberculosis. PMID- 8354546 TI - Evaluation of lactic dehydrogenase in cases of meningitis. AB - Lactic dehydrogenase (LDH) was measured serially in cerebrospinal fluid (CSF) and serum in 23 cases of meningitis (15 pyogenic and 8 tuberculous) and equal number of age and sex matched healthy controls to find out its diagnostic and prognostic significance in cases of meningitis. The LDH activity was significantly elevated in the CSF and serum (p < 0.001) in cases of pyogenic (PM) as well as tuberculous meningitis (TBM). The maximum elevation was seen on the 1st day and the activity declined thereafter. However, in 3 cases of PM and 5 cases of TBM, the LDH activity on subsequent estimations increased serially and all these cases died. Further, the basal LDH activity in the 3 cases of PM who died was significantly higher (p < 0.01) than those who survived. The rise in enzymatic activity in the CSF was significantly higher (p < 0.001) than in the serum in all the cases of meningitis. The LDH activity was significantly higher in PM as compared to TBM (p < 0.001) both in the CSF as well as the serum. PMID- 8354547 TI - Incidence of salmonella meningitis in Ludhiana (Punjab). AB - A retrospective study was carried out at Dayanand Medical College & Hospital, Ludhiana (Pb.) during the period from January 1985 to December 1990 to know the incidence of Salmonella meningitis. Salmonella etiology was established in 8 (3.43%) cases out of 233 cases of bacterial meningitis. Out of 8 cases, 7 were children under the age of 2 years. 4 Patients yielded S. typhimurium, 3, S. typhi and 1 S. senftenberg from cerebrospinal fluid samples. No Salmonella organism was isolated from blood cultures except one in which S. typhi was isolated. S. typhimurium was the predominant isolate showing multi drug resistance to commonly used drugs such as ampicillin, chloramphenicol, streptomycin, tetracycline and kanamycin. S. senftenberg also showed similar drug resistance pattern. S. typhi, on the other hand was sensitive to above antibiotics. PMID- 8354548 TI - Multiple drug resistance and genetic characterization of Salmonella typhimurium isolated at Chandigarh. AB - A total of 1072 strains of S. typhimurium were isolated in Chandigarh during 1985 1988. Genetic characterization of 'R' plasmids was attempted in 21 multiple drug resistant strains (ACKSSu TT p-19, ACKSSu, TP-I, AKSSu Tp-1). All the 21 strains were sensitive to gentamicin, furoxone and nalidixic acid. Level of resistance to different antimicrobial drugs varied from 200 to 1000 mg/L. Majority of the strains were untypable by the present set of 31 typing phages (Ut-17, Phage type 21-2, Phase type 99-2). All the plasmids belonged to class I transfer system. All the plasmids restricted some or all the typing phages of S. typhimurium and 39 also restricted phage phi 2. These plasmids belonged to F1me or I1 incompatibility groups and did not inhibit the function of fertility factor (fi ). PMID- 8354549 TI - The changing facets of Salmonellosis. PMID- 8354550 TI - Significance of serum immunoglobulin levels in conglomeration with trans-sternal phlebography in the phlebography management of breast cancer. AB - The study was conducted on 63 patients with breast lump and twenty normal healthy females. In benign breast disease, a significant (P < 0.001) rise in serum IgA, significant (P < 0.001) decrease in IgG and no change in IgM levels was seen before operation. A significant decrease (P < 0.001) in serum IgA and significant increase in IgG and IgM was observed post operatively. In carcinoma breast, a significant (P < 0.001) elevation in IgA, IgG and IgM levels was found pre operatively with a concomitant decrease in serum IgA and IgG and increase in serum IgM levels, post operatively. Trans-sternal phlebography (TSP) carried out with 95.23% success has revealed significant (P < 0.001) change in the staging of carcinoma breast. The increased levels of serum immunoglobulins associated with the patients of carcinoma breast with metastasis has led to conclude that these levels, if punctuated with TSP findings can lead to better assessment of the staging of carcinoma breast and thereby its management. PMID- 8354551 TI - Isolation of Capnocytophaga species from non-vital anterior teeth. AB - Root-canal infection is very common in India. Both aerobic and anaerobic organisms have been claimed for its aetiology. However, isolation of Capnocytophaga species from non-vital anterior teeth is sparse. In this study a solitary case of Capnocytophagal root canal infection is reported. PMID- 8354552 TI - Effect of levamisole as an immunomodulating agent in trophoblastic lesions. AB - Both cell mediated immunity and humoral immunity was assessed in 16 patients of hydatidiform mole and 6 patients of choriocarcinoma. Fifty percent patients of choriocarcinoma and 11 patients of vesicular mole were given levamisole (LVM) trial and were followed for 2 months. Absolute lymphocyte count (ALC) was significantly increased in vesicular mole after levamisole treatment but in choriocarcinoma no effect was obtained. Marked improvement of T cell rosette count was also seen in LVM treated patient of both vesicular mole (p < 0.001) and choriocarcinoma. Cutaneous DTH response to 2:4 DNCB in vesicular mole was also increased after LVM. Before treatment only 31.25% patients had strong cutaneous response but after treatment 53.35% patients had strong response, while cases of choriocarcinoma were unaffected. LVM also raised all the serum immunoglobulins (IgG, IgM, IgA) in both vesicular mole and choriocarcinoma. Hence, levamisole therapy was found to have a beneficial effect on both cellular and humoral immunity in the lesions of trophoblasts. PMID- 8354553 TI - Primary lymphoma of the brain. AB - In this study, clinical and histopathological features of primary lymphomas of the brain have been described in eight patients. The primary nature of lymphoma in these patients was confirmed by extensive clinical as well as radiological investigations and supported by a detailed histopathological examination. Computerised tomography (CT) scan showed multiple intra-cerebral lesion in two patients and in six patients the lesion was solitary. Although primary lymphoma of the brain carries poor prognosis, it is essential that these tumours should be accurately diagnosed as well as should be distinguished from secondary tumours. PMID- 8354554 TI - Sclerema neonatorum--histopathologic study. AB - Histopathological study of 10 cases sclerema neonatorum showed subcutaneous fibrosis with lobulation in all the cases. 8 (80 percent) cases showed non specific chronic inflammation of dermis and thinning of epidermis with atrophy of rete pegs and hypercollgenisation of dermis was evident in 70 percent cases. Fat necrosis with crystallisation of fat content was not a conspicuous feature. PMID- 8354555 TI - Morphological identification of Candida species on glucose agar, rice extract agar and corn meal agar with and without Tween-80. AB - A comparative study for the identification of 32 known strains of Candida species on the basis of morphology on glucose agar, rice extract agar and corn meal agar with and without Tween 80 revealed that when Tween 80 is incorporated in the media identification is possible for 96.8% of the species within 48 hours on rice extract agar and for 96.8% of the species within 48 hours on rice extract agar and for 90.6% of the species on glucose agar. The germ tubes and chlamydospores were also produced more on rice extract agar than on 0.1% glucose agar. Rice extract agar with Tween 80 can be used as single medium for morphologic identification of Candida species. The inoculated medium is first incubated at 37 degrees C for 3 hours and examined for germ tube formation and then incubated at 25 degrees C for 24 to 72 hours and examined for appearance of chlamydospores and mycelial morphology. PMID- 8354556 TI - Multi drug resistant Salmonella typhi in Ludhiana (Punjab). AB - 280 Salmonella typhi strains isolated from suspected cases of enteric fever during the year 1990 were studied for susceptibility to the antimicrobial agents chloramphenicol, ampicillin, cotrimoxazole, gentamycin, kanamycin, amikacin, ciprofloxacin by Kirby Baur disc diffusion method. All were blood culture positive cases. 63 strains (21.9%) were found resistant to chloramphenicol, ampicillin, cotrimoxazole, but sensitive to the amino glycosides and ciprofloxacin. Present study shows the prevalence of multi drug resistant Salmonella typhi in this region of Punjab. PMID- 8354557 TI - Prevalence of Nocardia species in the soil of Patiala area. AB - Five hundred soil samples were examined for Nocardia species in Patiala area by using paraffin bait technique. Forty (8 per cent) yielded Nocardia species. All the forty isolates identified as Nocardia asteroides were pathogenic to white mice. PMID- 8354558 TI - Acute renal failure in lymphoma of the kidney. AB - Involvement of kidney by lymphomatous process occurs in 30-40% of cases of lymphoma, if the disease is left untreated. Incidence of renal involvement at initial presentation is 2.7%-6%. Mostly it is in the form of insidious renal failure. Acute renal failure as initial manifestation of the disease is very rare. A case of lymphomatous involvement of the kidney, with initial presenting manifestation of ARF is discussed, and the mechanisms responsible for rarity of this is analysed. PMID- 8354559 TI - Rhinoentomophthoromycosis: a report of three cases. AB - Three cases of rhinoentomophthoromycosis involving the nasal region are presented diagnosis in the first two cases was made on surgical biopsy and in the third case by fine needle aspiration biopsy. A granulomatous inflammatory reaction was seen in tissue around hollow broad hyphae of the fungus. The hyphal strands were surrounded by eosinophilic deposits Splendore--Hoeppli phenomenon. PMID- 8354560 TI - Vasitis nodosa--a case report. PMID- 8354561 TI - Primary endodermal sinus tumour of the vagina: a case report. PMID- 8354562 TI - Digital and clavicular bone metastasis from transitional cell carcinoma of urinary bladder: a case report. PMID- 8354563 TI - Leiomyosarcoma of gallbladder: a case report. AB - A case of leiomyosarcoma of gallbladder, a rare tumor in hepatobiliary region, is reported. The present case differs from previously reported cases in its presentation with empyema of gallbladder and multiple intrahepatic cholangiolytic abscesses. Curative surgery could not be undertaken on account of poor condition of patient, and invasion of tumor into liver and adjacent organs. PMID- 8354564 TI - Multi drug resistant Salmonella typhi in Bombay. AB - An outbreak called 'Dombivali fever' started in March 1990 and spread rapidly all over Bombay and adjoining area. A concomitant and steady increase in multidrug resistant Salmonella typhi isolation was observed. Later this outbreak called 'Dombivali fever' was proved to be resistant typhoid fever only. The present paper deals with comparison of this outbreak with previous two years laboratory data from Sir J.J. Hospital, Bombay. A very high isolation rate of S. typhi (215 isolates) in 1990 as compared to 62 isolates in the last two years (1988-89), was observed in this laboratory. The incidence of multidrug resistance in cases of enteric fever (EF) was also very high (67.6%) in 1990, as compared to 6.2% in 1988 and 23.3% in 1989. All the strains tested in 1990 were sensitive to ciprofloxacin. PMID- 8354565 TI - Transferable drug resistance in Salmonella senftenberg. AB - Six Salmonella senftenberg strains were isolated from blood samples of patients clinically diagnosed to be suffering from enteric fever during the recent outbreak of enteric fever in and around Calcutta. All of them were multidrug resistant including chloramphenicol. The minimum inhibitory concentration (MIC) of the drugs in which they were resistant, were well above the normal level. All these strains were sensitive to cephalexin, gentamicin, furazolidone and ciprofloxacin. The transferable drug resistance test suggested that the strains were carrying transferable drug resistant gene containing ACSTK resistant factor. PMID- 8354566 TI - Atypical salmonellosis: two cases of sacroiliitis. AB - Two young adult males presented with fever, severe pain, redness, swelling over the left sacroiliac joint and inability to walk and squat. A differential diagnosis of tuberculous sacroiliitis was considered. On blood culture isolation of S. Typhi in both of them was suggestive of sacroiliitis of salmonella etiology. They recovered completely following specific antibiotic therapy, aspirin and bed rest. At recovery both showed extremely high Widal titres. PMID- 8354567 TI - Diagnostic utility of immunohistochemical techniques in intramedullary Schwann cell tumours. AB - Histopathologic features in two intramedullary schwann-cell tumours, closely resembled with those of fibrillary astrocytoma and could not be differentiated from each other by the conventional histochemical stains. However application of tumour markers-Glial fibrillary acidic protein (GFAP) and S-100 protein were found to be useful in differentiating these two tumours and thus helped in making an accurate histopathological diagnosis in these two patients. PMID- 8354568 TI - Assessment of past occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin using blood lipid analyses. AB - Current 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations were determined in blood samples for 138 persons who had been involved in assessment, clean-up and demolition activities after the 1953 BASF trichlorophenol reactor accident. From these data and detailed descriptions of the circumstances and duration of individual exposure, a regression model was developed for describing the relationships between various exposure situations and TCDD concentration. The model explained 65% of the variability in log (TCDD) concentration. Using half life assumptions and the regression model parameters we estimated cumulative TCDD concentrations back-calculated to the time of exposure for all 254 members of the accident cohort. The geometric mean cumulative TCDD concentration for all cohort members averaged 137.7 ppt. Estimated cumulative TCDD concentrations correlated well with chloracne severity. The mean TCDD concentrations were 38.4 ppt for the no chloracne subgroup (n = 139), 420.8 ppt for the moderate chloracne subgroup (n = 59) and 1008 ppt for the severe chloracne subgroup (n = 56). The estimation procedure should be helpful in assessing the relationships between various health outcomes and TCDD exposure in this cohort. PMID- 8354569 TI - Maternal occupation and congenital heart defects: a case-control study. AB - This paper reports a Swedish analysis of the possible effect of maternal occupation on the occurrence of congenital heart defects. The analysis included 3324 infants (1108 cases and 2216 controls) born during the period 1982-1986. Information on maternal occupation was retrieved using two sources: the 1985 census and the Medical Birth Registry. A comparison between these two sources using the information on mothers of 756 infants born in 1986 showed a good concordance although 11% of the women were reported with a different employment status. No association appeared between the type of maternal occupation and the occurrence of infant congenital heart defects although some odds ratios were slightly above 1. PMID- 8354570 TI - Urinary N-acetyl-beta-D-glucosaminidase and beta-aminoisobutyric acid in workers occupationally exposed to metals such as chromium, nickel, and iron. AB - To examine the relationships between the urinary excretion of N-acetyl-beta-D glucosaminidase (NAG) and beta-aminoisobutyric acid (AIBA) as a metabolite of thymine, and exposure to chromium, nickel, and iron, we determined these parameters in 58 workers engaged in the cutting and grinding of stainless steel or iron-steel plates. A significant increase in urinary NAG activity or urinary AIBA excretion was found in some of these workers. However, we could not find a significant positive correlation between the urinary excretion of NAG or AIBA and the urinary concentration of chromium, nickel, or iron as an indicator of internal dose. PMID- 8354571 TI - Work noise annoyance and blood pressure: combined effects with stressful working conditions. AB - In a community-based cross-sectional study (n = 174, 68% participation), we examined the effect on blood pressure of occupational noise annoyance and its combined effect with social support at work, nightshift work, and work satisfaction. In a multivariate analysis the effect of noise annoyance alone (mean difference, 95% CI) was 2.1 (-3.0, 7.3) mmHg for systolic and 3.5 (0.3, 7.4) mmHg for diastolic blood pressure (n = 44). The combined effect with low work satisfaction was 7.5 (0.0, 15.0) mmHg systolic and 6.3 (0.6, 12.4) mmHg diastolic (n = 18). With nightshift work the effect was 5.0 (-2.4, 12.4) mmHg on systolic and 8.1 (2.5, 13.7) mmHg on diastolic blood pressure (n = 15). The findings for social support were inconsistent. The results suggest that analysis of main effects only may underestimate the true public health impact and underline the necessity of searching for combined effects of environmental stressors. PMID- 8354572 TI - The effectiveness of respirators measured during styrene exposure in a plastic boat factory. AB - In a plastic boat company we studied workers' attitudes toward wearing respiratory protective equipment and differences in styrene exposure received with and without respirators. The workers studied used either half-facepiece air purifying or full-face air-supplied respirators as much as possible during the first day of the study. On the second day respirators were used only for short periods or not at all. Individual styrene exposures were measured by personal air sampling in the breathing zone. When using respirators the exposure was measured both inside and outside the respirators. The styrene metabolites mandelic and phenylglyoxylic acids were determined in urine samples collected during the workday. The eleven workers studied used the respirators 52% of the time on the first day and 7% of the time on the second. The reasons for not wearing respirators were that they delayed work, were too tight and uncomfortable, made it difficult to breath, and/or became too warm. The use of respirators during work operations such as spraying, laminating, and painting reduced the styrene exposure by 56%-92%. The excretion rate of mandelic and phenylglyoxylic acids in urine collected at the end of the working day was 30%-99% lower when respirators were worn than when they were not. PMID- 8354573 TI - Occupational exposure and lung cancer risk in a coastal area of northeastern Italy. AB - A case-control study of lung cancer and occupational exposure was conducted in a coastal area of Northeastern Italy where metallurgical and mechanical industries, docks and shipyards are located. Cases comprised 756 men who died of primary lung cancer in a 5-year period. Controls comprised 756 male subjects dying from other causes during the same period. Occupational exposures to lung carcinogens were assessed according to a job title-based approach, using two separate lists of industries/occupations recognized as being causally associated (list A) or suspected of being causally associated (list B) with lung cancer in humans. Exposure to asbestos was classified as absent, possible, or definite. After adjustment for cigarette smoking and place of residence, a significant association was found between lung cancer and occupations in both list A [relative risk (RR) = 2.25, 95% confidence interval (CI) = 1.68-3.03] and list B (RR = 1.33, 95% CI = 1.03-1.71). A significant excess risk was found for workers with definite exposure to asbestos as compared to those with no exposure to lung carcinogens (RR = 1.98, 95% CI = 1.42-2.75). Among occupations with recognized exposure to lung carcinogens other than asbestos, a significant excess risk for lung cancer was observed in iron and metalware workers. In occupational groups with definite exposure to asbestos, elevated risk estimates were found for shipyard workers, dockworkers, carpenters, and electricians. The combined effect of smoking and asbestos was found to be compatible with that expected under a multiplicative model. The overall population-attributable risk (ARp) for cigarette smoking was found to be 87.5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354574 TI - Occupational exposure to hexahydrophthalic anhydride: air analysis, percutaneous absorption, and biological monitoring. AB - Urinary hexahydrophthalic acid (HHP acid) levels were determined in 20 workers occupationally exposed to hexahydrophthalic anhydride (HHPA) air levels of 11-220 micrograms/m3. The levels of HHP acid in urine increased rapidly during exposure and the decreases were also rapid after the end of exposure. The elimination half time of HHP acid was 5 h, which was significantly longer than in experimentally exposed volunteers, possibly indicating distribution to more than one compartment. There was a close correlation between time-weighted average levels of HHPA in air and creatinine-adjusted levels of HHP acid in urine collected during the last 4 h of exposure (r = 0.90), indicating that determination of urinary HHP acid levels is suitable as a method for biological monitoring of HHPA exposure. An air level of 100 micrograms/m3 corresponded to a postshift urinary HHP acid level of ca. 900 nmol/mmol creatinine in subjects performing light work for 8 h. Percutaneous absorption of HHPA was studied by application of HHPA in petrolatum to the back skin of three volunteers. The excreted amounts of HHP acid in urine, as a fraction of the totally applied amount of HHPA, were within intervals of 1.4%-4.5%, 0.2%-1.3%, and 0%-0.4% respectively, indicating that the contribution from percutaneous absorption is of minor importance in a method for biological monitoring. PMID- 8354575 TI - Biochemical and physiological aspects of 2,5-hexanedione: endogenous or exogenous product? AB - This article reports results regarding two different physiological aspects of 2,5 hexanedione (2,5-HD). The first is the relationship between "free" 2,5-HD (the fraction of "real" 2,5-HD) and "total" 2,5-HD (2,5-HD obtained from acid hydrolysis) in urine and blood of workers exposed to n-hexane. The second part of the study is an attempt to clarify "physiological" excretion of 2,5-HD in subjects not occupationally exposed to n-hexane. The concentration of free 2,5-HD in urine of workers exposed to n-hexane is about 8% of total urinary 2,5-HD. In blood, free 2,5-HD is about 50% of the total. The serum concentration range of total and free 2,5-HD in workers from whom blood was taken was 33-418 micrograms/l and 14-283 micrograms/l respectively. In subjects not exposed to n hexane, urinary concentration of 2,5-HD ranged between 0.17 and 0.98 mg/l, the urinary excretion rate between 0.23 and 0.57 microgram/min, and renal clearance between 14 and 66 ml/min. The blood concentration of 2,5-HD in nonexposed subjects was 6-30 micrograms/l. Fluctuations typical of a circadian rhythm were not observed for 2,5-HD in blood or urine. We think that 2,5-HD is mainly a product of intermediate metabolism in the human body. Only a minimal part could derive from n-hexane as a ubiquitous micropollutant. PMID- 8354576 TI - Cadmium, zinc, copper, and metallothionein levels in the kidney and liver of inhabitants of upper Silesia (Poland). AB - The levels of Cd, Zn, Cu and metallothionein (MT) were determined in renal cortex and liver of 75 subjects decreased in the period 1986-1989 in the area of Upper Silesia (Katowice). The mean age of the population studied was 53.6 +/- 14.6 years. The determined levels (mean +/- SD) were: 43.1 +/- 23.5 micrograms Cd/g; 52.5 +/- 17.4 micrograms Zn/g; 2.2 +/- 0.7 microgram Cu/g; 0.80 +/- 0.36 mumol Hg/g in renal cortex and 3.5 +/- 2.5 micrograms Cd/g; 82.8 +/- 34.3 micrograms Zn/g; 4.5 +/- 2.6 micrograms Cu/g; 0.69 +/- 0.44 mumol Hg/g in the liver. The level of Cd in renal cortex was 40% higher in smokers compared to nonsmokers and was independent of the gender. Whole-body retention of Cd was 34.1 +/- 18.5 mg; smoking elevated the value from 27.1 to 38.2 mg. Compared with a similar study made in central Poland (Lodz), a significant difference was found only regarding the level of Zn and MT in the liver, pointing to the possibility that exposure to this element in the region of Upper Silesia may be higher. PMID- 8354577 TI - Prevalence of objective eye manifestations in people working in office buildings with different prevalences of the sick building syndrome compared with the general population. AB - A cross-sectional clinical epidemiological study was carried out among 169 office workers in four Copenhagen town halls with different prevalences of the sick building syndrome. The results were compared with those in 112 subjects randomly selected from the general population. Biomicroscopic eye manifestations, such as premature break-up of the precorneal tear film, absence of foam at the inner eye canthus and epithelial damage of the bulbar conjunctiva, were investigated together with self-reported eye complaints. Although intercorrelated, the objective eye manifestations independently were statistically associated with self-reported eye complaints in office workers. The prevalence of the objective eye manifestations was significantly elevated in office workers compared with the general population and most pronounced for the buildings with a high prevalence of the sick building syndrome (P < 0.001). In the general population, subjects with a non-industrial occupation, including office workers, had a significantly higher prevalence of objective eye manifestations than those with an industrial occupation (P = 0.03), but the prevalence was still significantly lower than that among the office workers in buildings with a high prevalence of the sick building syndrome (P < 0.001). Since possible confounders were found not to explain the difference in prevalence of objective eye manifestations and complaints among the two populations, it is concluded that the office environment (buildings and/or type of office work) promotes these objective changes accompanied by self reported complaints. PMID- 8354578 TI - Biological monitoring of occupational exposure to n-hexane by measurement of urinary 2,5-hexanedione. AB - Occupational exposure to n-hexane in shoe factory workers was monitored by measuring urinary 2,5-hexanedione, the major metabolite of this solvent and the probable cause of peripheral neuropathy in exposed workers. Solvent pollution was monitored in the work environments of 189 employees, of whom 123 (65%) worked in Alicante, Spain, and 66 (35%) in Veneto, Italy. 2,5-Hexanedione was measured in spot urine samples collected from workers at the end of the shift. Information on working conditions was obtained from a previous study. A significant linear correlation was found between mean environmental concentration of n-hexane and urinary concentration of 2,5-hexanedione. The variability in the correlation may have been due to the variable use of protective clothing (gloves), and to variations in exposure during the working week. In numerous workers, percutaneous absorption of n-hexane represented as much as 50% of the total absorbed dose. Urinary concentrations of 2,5-hexanedione tended to increase during the working week. Simultaneous exposure to n-hexane and toluene tended to reduce urinary excretion of 2,5-hexanedione, whereas exposure to n-hexane and methyl ethyl ketone tended to increase excretion of the metabolite. PMID- 8354579 TI - Elbow joint disorders in relation to vibration exposure and age in stone quarry workers. AB - Elbow joint disorders were studied in relation to vibration exposure and age in 74 male stone quarry workers who operated mainly chipping hammers and sometimes rock drills. They were examined for range of active motion in elbow extension and flexion, and by means of radiographs of the elbow joint. Effects of age and vibratory tool operation on the elbow joint were statistically estimated using multiple regression analysis. In the analysis of all subjects, including those aged over 60 years, age was significantly related to the range of motion in extension and to radiographic changes in both elbows, and the duration of vibratory tool operation was associated with the range of right elbow flexion. Among subjects under the age of 60 years, duration of vibratory tool operation showed a significant dose-effect relationship to the range of flexion and radiographic changes in the right elbow, but there was no significant relationship with age. The present results suggest that the operation of chipping hammers and rock drills contributes to elbow joint disorders or osteoarthrosis, even when the effect of age is taken into account. Besides vibration exposure, it may be necessary to consider various loads on the elbow joint such as firmly grasping and pressing the tool against stones with the arm bent at about 90 degrees, and carrying stones. PMID- 8354580 TI - The development of mechanical circulatory systems: "the labors of Hercules". PMID- 8354581 TI - Must we treat uremic dyslipidemia? PMID- 8354582 TI - Detection of low molecular size lipopolysaccharide contaminated in dialysates used for hemodialysis therapy with polyacrylamide gel electrophoresis in the presence of sodium deoxycholate. AB - Dialysis membranes are generally considered to be impermeable for bacterial endotoxin (lipopolysaccharide, LPS) contaminated in dialysates used for hemodialysis therapy, since LPS molecular size in aqueous media has been reported to be more than 10(6). However, there are few reports concerning its size in dialysates. We have already presented a newly developed polyacrylamide gel electrophoresis with sodium deoxycholate (DOC-PAGE) which proves the LPS size. Using this method, therefore, we attempted to clarify the size of LPS in dialysates. We demonstrated that LPS in dialysates had roughly two different molecular sizes with DOC-PAGE and that compared to migration profiles of Salmonella LPS as controls on DOC-PAGE, one molecular size of LPS was approximately 4,000 and the other in tens of thousands. This investigation indicates the possibility of LPS transfer across dialysis membranes. PMID- 8354583 TI - Ticlopidine improves dialysis clearance of solutes in uremic patients by reducing blood clotting in dialyser fibers. AB - Ticlopidine, a platelet aggregation inhibitor was tested, in a double blind comparative cross-over study versus placebo, in 51 dialysed uremic patients who had increased dialyser blood clotting (> 25 fibers clotted/dialyser). At the end of a 7-day treatment period with 250 mg daily, the clearance of urea, creatinine and phosphate was determined at 30 and 210 minutes of dialysis, as well as the number of fibers clotted at the end of dialysis. Ticlopidine improved dialyser clearances for urea, creatinine and phosphate from 165 +/- 41 to 182 +/- 35 (p < 0.01), 135 +/- 37 to 143 +/- 35 (p < 0.05), and 120 +/- 36 to 130 +/- 35 (p < 0.05) ml/min, respectively, at 30 min of HD and a similar effect was seen after 210 min of dialysis. The number of dialyser fibers clotted after dialysis was reduced by ticlopidine therapy from 110 +/- 48 to 15 +/- 8 (p < 0.01). Ticlopidine reduced the initial dialysis-induced drop in leucocyte count by 20% (p < 0.05); no change in platelet or erythrocyte count was observed. Two out of 51 patients experienced an adverse reaction from ticlopidine (cutaneous haematoma and minor gingival bleeding). We conclude that ticlopidine is an efficient and safe drug for dialysed uremic patients since it can reduce blood clotting and thereby increase dialysis efficiency. PMID- 8354584 TI - Catheter-implanted prosthetic heart valves. Transluminal catheter implantation of a new expandable artificial heart valve in the descending thoracic aorta in isolated vessels and closed chest pigs. AB - A new expandable artificial heart valve was developed for implantation by a transluminal catheter technique without using thoracotomy or extracorporeal circulation. The aim of this study was to implant the valve in isolated vessels of the descending thoracic aorta as well as in closed chest pigs, and furthermore to study the prosthesis' mechanical stability and the valve function. The artificial valve was made by mounting a porcine aortic valve on an expandable stent. Before implantation, the stent-valve was compressed on a deflated balloon catheter and mounted inside an introducer sheath. After intravascular introduction to the descending thoracic aorta the stent-valve was discharged from the sheath. Implantation was performed by balloon inflation which expanded the stent-valve to a diameter exceeding the internal vessel's diameter. After balloon deflation the stent-valve maintained an expanded configuration ensuring a stable fixation against the vessel wall. In vitro implantations were performed in 36 isolated descending thoracic aorta specimens obtained from 80 kg pigs. Mechanical stability was evaluated by applying a downing load to the prosthesis. No displacement occurred at loads < or = 1 kg when a large balloon (31 mm) was used for implantation. Transvalvular pressure differences between 11-47 mmHg (median) were obtained at antegrade flowrates between 5-8 l/min. Furthermore, only moderate leakage flows were measured during retrograde perfusion. In vivo implantations were performed in six 80 kg pigs. Implantation was safe and easy, and angiograph and haemodynamic evaluations revealed essentially no stenosis or regurgitation. No complications in migration, perforation, hemorrhage or thrombosis were observed. This study indicates a good mechanical stability and valve function of the new expandable artificial valves. PMID- 8354585 TI - Heparinization of biological vascular graft reduces fibrin deposition. AB - An alternative graft is needed for coronary bypass operations in patients lacking suitable autologous vessels. We therefore studied Denaflex, a biologic graft, in a dog ex-vivo shunt model to determine whether heparin treatment makes this graft less thrombogenic. Comparison was also made to Bioflow, a nonheparinized biologic graft. Fibrinogen deposition during high flow (593 +/- 202 ml/min) decreased from 672 +/- 467 ng/mm2 in nonheparinized Denaflex grafts to 448 +/- 298 ng/mm2 (p < 0.05) in heparinized Denaflex grafts. At low flow (117 +/- 13 ml/min), heparinization of Denaflex grafts similarly decreased fibrinogen deposition from 1102 +/- 601 ng/mm2 to 703 +/- 405 ng/mm2 (p < 0.05). At both flow rates fibrinogen deposition in Bioflow grafts was less than in nonheparinized Denaflex, but was similar to heparinized Denaflex grafts. Platelet deposition was not influenced by heparinization of Denaflex grafts and was similar among Denaflex and Bioflow preparations. Whether Denaflex performs acceptably in vivo as a xenograft requires extensive study. PMID- 8354586 TI - Use of the microdialysis technique in the monitoring of subcutaneous tissue glucose concentration. AB - For some time the subcutaneous (s.c.) tissue has been the target for continuous glucose measurement. The microdialysis technique permits an extracellular region approach, which has been used for about two decades for measuring various metabolites in dialysates obtained from different body regions. By connecting a s.c. implanted microdialysis probe to a flow chamber of an amperometric glucose sensor, the procedure of glucose sensing was transferred to ex vivo. Using this device it was possible to obtain, for up to 24 hours, s.c. tissue glucose profiles of healthy and diabetic people. The microdialysis theory, the calibration process and other microdialysis technique applications are discussed in this paper. Although the combination of the microdialysis technique and amperometric glucose sensing requires certain technical equipment, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system. PMID- 8354588 TI - Parathyroidectomy: whom, when, how? PMID- 8354587 TI - Morphological response of the peritoneum and spleen to intraperitoneal biomaterials. AB - The present study was performed to evaluate the morphological response of the peritoneum and spleen to biomaterials. Silicone elastomer, knitted dacron or rubber was implanted, respectively, into a rat's peritoneal cavity and the morphology of the peritoneum and spleen was studied at 4 hours and on the 1st, 4th, 7th and 21st day after surgery. The morphological changes were identical among groups with different implanted materials. After intraperitoneal implantation of biomaterials from 4 hours and on, an infiltration of inflammatory cells was found in the slackened edematous superficial part of the peritoneum. Also noted in the spleen were stasis, vessel dilatation and fibrin deposition. With the help of scanning electron microscopy, a marked denudation and separation of the mesothelial cells, with infiltration of inflammatory cells, were observed. Peripheral leucocytes significantly increased in number one day after intraperitoneal implantation. Three weeks after intraperitoneal implantation, the materials were completely encapsulated and the morphological aberration of the peritoneum and spleen disappeared. The findings reveal the consequence and the resolution of the host-biomaterial interaction, which could contribute to the explanation of various pathophysiological alterations, including the translocation of enteric bacteria and the development of infectious complications after intraperitoneal biomaterial implantation. PMID- 8354589 TI - Use of gentamicin physiologically-based model for individual dosing. AB - A new approach to fixing initial doses of gentamicin (GM) for i.m. administration (that is most commonly used anyway) is discussed. This approach is based on a physiologically-based model allowing to reproduce individual patterns of GM concentration change in the patient's blood. This approach was used to reproduce the individual pattern of GM concentration change after the initial i.m. administration of 80 mg to 19 male patients (age-range 21 to 73 years, weight range 50-94 kg, creatinine concentration in the blood 0.4-1.6 mg/d). The GM concentration levels, obtained with the help of this model, were afterwards compared to the results of FPIA measurement of GM concentrations in the blood of the patients 0.5, 1, 2, 3, 5 and 7 h after administration. It proved that the average deviation of the predicted values from the actual was equal to 20 per cent for all the measuring time-points. For comparison we used individual patterns of GM distribution in blood calculated according to the one-compartment model from the same values of Vd, Cl and dose. In this case the error of pharmacokinetic prediction exceeded the 20 per cent and amounted to 43 per cent by 0.5 and 7 hours. Thus, the new approach with the physiologically-based model provides better accuracy for stable pharmacokinetic prediction for longer stretches of time upon administration, which is especially important for the correct establishment of dosing intervals. PMID- 8354590 TI - Lack of activities of amikacin and sulphamethoxazole against Mycobacterium avium intracellulare. AB - Twenty clinical isolates of Mycobacterium avium-intracellulare were tested with amikacin and sulphamethoxazole for in-vitro susceptibilities. The MICs and MBCs of the former drug ranged from 8 to > 64 mg/L (median MIC: 64 mg/L, median MBC: > 64 mg/L). The MICs and MBCs of the latter drug were found to be > 256 mg/L. Each of eight patients with invasive pulmonary disease due to these organisms was treated with amikacin for six months and with cotrimoxazole (sulphamethoxazole trimethoprim) for one year. Only one patient had sustained bacteriological conversion. Three patients showed a transient reduction of bacillary load during the period of amikacin administration. The rest all failed to show response. Thus sulphamethoxazole was found to have no activity against Mycobacterium avium intracellulare, and amikacin has doubtful activity when used alone in treatment of M. avium-intracellulare infection. PMID- 8354591 TI - Effects of some cephalosporins and teicoplanin on platelet aggregation. AB - Antibiotics may interfere with platelet (PLT) function, and beta-lactam antibiotics may interact with PLT aggregation, by inhibiting the binding of agonists of this aggregation (such as ADP and collagen) to specific receptor sites. In this study we have evaluated the relative in-vitro antiplatelet effects of some old and new cephalosporins (cefonicid, ceftazidime, ceftriaxone, cefotaxime, cefuroxime and flomoxef) and of teicoplanin, a new glycopeptide antibiotic. All the cephalosporins tested, and also teicoplanin, were found to have the potential to adversely affect human platelet aggregation only at high concentrations which are not achieved in vivo. PMID- 8354592 TI - Oral ciprofloxacin for treatment of chronic osteomyelitis. AB - Seventeen adult patients with chronic osteomyelitis were treated with oral ciprofloxacin, 750 mg twice daily. Treatment ranged from 28 to 254 days. Efficacy was considered to be good, based upon clinical resolution observed in 13 patients (76%). Clinical and microbiological failure was observed in 3 patients (18%), and there was one case of reinfection. Tolerance was very satisfactory, since the adverse reactions were mild and transitory; these occurred in 7 patients (41%), being cutaneous rash in 4 patients and diarrhoea in 3 patients. No patient had to discontinue treatment. Thus, oral ciprofloxacin may be useful option for the prolonged treatment of chronic osteomyelitis, provided that it is always associated with surgical debridement. Due to the probable development of ciprofloxacin resistance in the S. aureus multiresistant strain, already observed in two patients in the present investigation, it is suggested that for the treatment of such infections another drug with antistaphylococcal activity should be associated with the ciprofloxacin. PMID- 8354594 TI - L-carnitine in cardiogenic shock therapy: pharmacodynamic aspects and clinical data. AB - Following our previous work on biochemical and clinical aspects of cardiogenic shock, we carried out an open study on 27 patients hospitalized in shock condition and investigated for the entire period of permanence in intensive care units (ICU). The subjects were treated with high doses of L-carnitine following previous results on the use of this molecule in conditions of oxidative damage due to acute cellular hypoxia. When compared with the data reported in the literature, the results obtained in this study show a surprisingly positive trend for the carnitine-treated patients in terms of survival rate to the cardiogenic shock. This finding and statistical analysis of the clinical parameters confirm the suggestion that L-carnitine could be credited with a new and interesting role in the therapy of cardiogenic shock. PMID- 8354593 TI - Oral ciprofloxacin for treatment of severe infections. AB - Twenty adult patients with severe infections were treated with oral ciprofloxacin, 500 or 750 mg twice daily. Treatment ranged from 8 to 25 days. Efficacy was good: 14 patients (70%) were cured, four (20%) improved and there were only two (10%) failures. Tolerance was very satisfactory, the most common side-effects being mild gastrointestinal symptoms (three patients). Only one adverse laboratory result was observed: a transient rise in blood urea nitrogen and creatinine levels. None of the adverse effects led to discontinuation of treatment. Thus, ciprofloxacin presents as a promising drug for treatment of severe infections caused by susceptible organisms when ambulatorial therapy, at least during a large part of the treatment, is possible and desirable. PMID- 8354595 TI - Pharmacokinetic study of the relative bioavailability and bioequivalence after oral intensive or repeated short term treatment with two polyamino acid formulations. AB - The authors studied the relative bioequivalence and bioavailability of two oral polyamino-acid formulations (packet and flacon), based on 4 amino acids (L glutamine, L-phosphoserine, L-phosphothreonine and L-arginine) in association with vitamin B12 (Bio-logos, Sigma Tau Pharma S.A). Open-trial testing was carried out after intensive treatment and on the attainment of sustained levels. 50 healthy volunteers (27 males, 23 females), ranging in age from 23 to 32 years, were included in the study. The pharmacokinetic behaviour of the various active ingredients was examined at a haematic level. Possible undesirable side-effects, resulting from treatment, were also examined during the study. The mean pharmacokinetic constants considered (Ke1, Cmax and t1/2) generated an almost overlapping AUC (area under the curves) for all homologous components contained in both pharmaceutical forms. This indicates almost complete bioequivalence. The mean index for the rate of relative bioavailability was, in fact, estimated to be 106.3 +/- 12.4%. Repeated treatment did not appear to disturb the absorption mechanisms of the active ingredients contained in either of the two formulations examined, maintaining the relative bioavailability relationship within a negligible range, with a statistically non-significant difference (Student's t test for coupled data). A few episodes, characterized by slight increases in excitability, were reported for both preparations in two patients (4%). PMID- 8354596 TI - Interactions of Ostertagia species with their bovine and ovine hosts. AB - Ostertagia spp. affect their hosts in several complex interactions involving structural, biochemical, hormonal, nutritional and immunological mechanisms. Following infection with Ostertagia spp. the specialised secretory function and junctional integrity of gastric epithelial cells is lost. The pH of the abomasal contents is elevated and pepsinogen concentration in the plasma increases. There is a concurrent elevation in the concentration of blood gastrin. The effects may be a response to the physical interaction of parasite with epithelial cells, may be mediated through parasite excretory/secretory products, or by neural mechanisms. There may also be interactions between the responses since elevated abomasal pH stimulates secretion of gastrin. Hormonal changes may also have a role in the increased susceptibility of host to parasite during the periparturient period. Prolactin was considered the most likely hormone candidate although there is now a body of evidence to suggest that elevated prolactin concentrations are not solely responsible. Infection with Ostertagia spp. causes a marked inappetance, negative nitrogen balance and reduction in apparent gross energy digestion. The level of nutrition may also affect the response of the host to the parasites and establishment of O. circumcincta is lower in animals on a low plane of nutrition than those on a high plane. Immunity of Ostertagia spp. develops slowly and once established is manifest following challenge by an initial hypersensitivity response, followed by a cell mediated response and then an antibody response. Parasites may fail to establish or may be expelled from immune animals and if they do establish may be stunted with small vulval flaps and lower biotic potential and may become inhibited at the early fourth stage of development. PMID- 8354597 TI - Influence of sex and reproductive status on susceptibility of ruminants to nematode parasitism. AB - Bulls and rams are notorious among stockmen and stud breeders for their apparently greater susceptibility than cows, ewes, steers or wethers to diseases caused by excessive infection with parasitic nematodes. Extension advice given to farmers generally includes a recommendation to treat entire male animals as though they were weaners. In contrast, the scientific literature contains little documentation of this fact, although the phenomenon has been well-described in laboratory animals. Scientific interest in the susceptibility of lactating cows and especially ewes to nematode parasitism has been more extensive, but unproductive in terms of elucidating responsible mechanisms. Where ewes have acquired immunity to nematode infection, they tend to lose it around the time of parturition and during lactation, with important epidemiological and productivity consequences. In strains of sheep selected for resistance to nematode infection, principally through a more rapidly acquired immune response, resistant ewes still undergo a periparturient loss of immunity but retain their relative superiority over unselected or susceptible ewes. The mechanisms involve effects of hormones associated with lactation on the immune system, but an unequivocal role for prolactin or any other hormone has not yet been identified. Collaboration between immunologists, endocrinologists and parasitologists is required. PMID- 8354598 TI - The effect of age and dietary protein on immunity and resistance in lambs vaccinated with Trichostrongylus colubriformis. AB - Development of immunity and resistance to Trichostrongylus colubriformis was measured in sheep, 8-26 or 33-51 weeks of age, that were offered two levels of dietary protein (11 and 20%). Resistance to challenge infection was ascertained by measuring worm burden, faecal egg count and eggs in utero in the nematode. Development of immunity was measured by an in vitro lymphocyte blastogenesis test to T and B cell mitogens and to somatic antigen from infective (L3) larvae. Young lambs offered the low protein diet showed a significantly lower resistance to parasites than older animals. The young animals on the high protein diet developed better resistance. Age and dietary protein influenced in vitro T lymphocyte responses to parasite antigen and mitogens, which were particularly well developed in vaccinated lambs on the high protein diet. Lymphocyte responsiveness to L3 larval antigen was negatively correlated with parasite status in vaccinated older lambs, and may be important in the development of acquired resistance to T. colubriformis. PMID- 8354599 TI - The effect of feed intake on the rate of flow of digesta and the disposition and activity of oxfendazole in sheep. AB - Within 3 h of intra-ruminal (IR) administration oxfendazole (OFZ) was extensively associated with digesta particulate material. This association appeared to be a passive adsorption/desorption since sheep given dose equivalent OFZ which was contained solely in rumen particulate digesta (obtained from OFZ treated donor sheep) exhibited similar OFZ disposition to the IR treated animals. The association of OFZ with rumen particulate digesta is a major determinant of the pharmacokinetic behaviour of OFZ. The kinetic disposition of OFZ was compared in sheep fed 400 g and 800 g day-1 of 50:50 lucerne/wheaten chaff. The flow rate of rumen and abomasal fluid and particulate digesta increased with feed intake whilst the availability of OFZ and its metabolites in the digestive tract and bloodstream decreased. Compared to untreated sheep fed 800 g day-1, OFZ did not affect benzimidazole (BZ) resistant Trichostrongylus colubriformis, but reduced the numbers of BZ-resistant Haemonchus contortus by 61%. When sheep were fed 400 g day-1 36 h before and after OFZ administration, 60% of T. colubriformis and 94% of H. contortus were removed. Elevated anthelmintic efficacy in sheep can therefore be obtained when gastric flow has been slowed by temporarily reducing feed intake. PMID- 8354600 TI - Host genes, parasites and parasitic infections. AB - Resistance to infection of mammalian hosts by parasites is under genetic control at many different levels: between species, between races, breeds and lines of single species and between individuals. These genetic effects have been described in many host-parasite systems. Here we review the interaction between three elements: host genes, parasites and the environment in which parasitic infections develop. Already livestock industries exploit genetic variation between breeds, particularly for the control of trypanosomiasis and tick infestation in cattle. In most populations, and to many diseases, resistance is heritable and selective breeding for resistance in commercial livestock species has been successful experimentally. Attempts at utilizing genetic variation are placed in the broad context of the coevolution of host and parasite, the limited knowledge we have of the mode of action of resistance genes and our ability to use genetic information to predict resistance to parasites. PMID- 8354601 TI - Calibrating the bootstrap test of monophyly. AB - It has been suggested that the bootstrap test of monophyly is too conservative, i.e. the test rejects the hypothesis of monophyly when it is true far too often. Here, a method called the iterated bootstrap is described which estimates by randomization the probabilities associated with rejecting the hypothesis of monophyly when it is true and accepting the hypothesis of monophyly when it is false. Using this method, the bootstrap test can be calibrated by taking account of the errors associated with the hypothesis test. This method is applied to the high-level phylogeny of the Platyhelminthes using 18S rRNA sequences. The analysis suggests that the data cannot unequivocally resolve the placement of the Platyhelminthes with respect to the Annelida and Insecta. PMID- 8354602 TI - Affinities of the Gyliauchenidae: utility of the 18S rRNA gene for phylogenetic inference in the Digenea (Platyhelminthes). AB - 18S rRNA sequences were analysed using parsimony and distance matrix methods to infer relationships among 8 species of trematodes. In particular, the disputed relationships of the digenean family Gyliauchenidae were examined. This family is regarded by some to be close to the Lepocreadiidae, and by others to be close to the Paramphistomidae. The data gave very strong support for placing the Gyliauchenidae close to the Lepocreadiidae, and almost no support for the alternative hypothesis. This support was found, regardless of the method of analysis, using data from different regions of the molecule as well as from the entire molecule. Morphological features are re-interpreted in the light of this conclusion. PMID- 8354604 TI - The role of nematophagous fungi in the biological control of nematode parasites of livestock. AB - The control of nematode parasites of livestock is presently based entirely on anthelmintic treatment and grazing management. On their own, these methods are not sustainable because parasites invariably develop resistance to anthelmintics and because of increasing public concern about chemical residues in livestock products and the environment. Although alternative, non-chemotherapeutic control strategies, such as vaccines and genetic selection for resistance are the focus of considerable research activity worldwide, biological control of nematode parasites has been virtually ignored. The little work that has been done is restricted largely to western Europe and involves virtually just one fungal species, namely Arthrobotrys oligospora. More recent studies indicate other known nematophagous fungal species are more efficient predators of infective larvae in sheep faeces than A. oligospora, and others have a greater capacity to survive passage through the gastrointestinal tract of ruminants. These findings plus the relatively sparse numbers of microbial competitors in the fresh faecal environment, compared with the plant rhizosphere where biological control of plant parasites is proving a particularly intractable problem, engenders optimism that the biological control of animal parasitic nematodes may become a practical reality. Such control will never be a substitute for chemotherapy, where the primary purpose is worm removal from the host, but should be incorporated together with other options into integrated pest management systems to provide sustainable nematode control of livestock into the twenty-first century. PMID- 8354603 TI - Phylogenetic position of Heronimus mollis (Digenea): evidence from 18S ribosomal RNA. AB - Most (1918bp) of the nucleotide sequence of the 18S ribosomal RNA gene of Heronimus mollis was determined. We aligned this sequence with 18S rRNA sequences from 7 other digeneans and an aspidobothrean. Using these data we explored the phylogenetic position of H. mollis. No support was found for the hypothesis that H. mollis is the sister taxon of the remaining digeneans examined here; similarly, no support was found for the hypothesis that H. mollis is closely related to the paramphistomes. These analysis together with the skewness of the frequency distribution of the lengths of 100,000 trees sampled randomly from the set of all possible trees (generated from these data) indicate that 18S rRNA sequences are valuable for phylogenetic inference in the Digenea. PMID- 8354605 TI - Modified Nissen fundoplication in the treatment of gastroesophageal reflux disease. AB - Twenty-five consecutive patients underwent a primary modified Nissen fundoplication for gastroesophageal reflux disease. According to this procedure, an increase of the diameter of the gastric wrap to a comfortable passage of the surgeon's index finger between oesophagus and gastric wrap was obtained, while the length of the gastric wrap was 1.0 cm. The fixation of the wrap on the anterior wall of the oesophagus was done at the level of the mucosal cardia 1.0 cm above the gastroesophageal junction strengthened by four mesh pledgets. Two more stitches between the seromuscular layer of the gastric fundus and the oesophageal musculature were placed to prevent reduction of created oesophagogastric intussusception. The results of this modified Nissen procedure are excellent during the early postoperative follow-up period, ranging from 10 to 45 months and averaging 26 months. PMID- 8354606 TI - Auxiliary liver transplantation in the pig without portal blood: a study of a new technique for application to the heterotopic hepatic xenotransplant. AB - An auxiliary liver transplantation surgical technique in the pig, in which the graft only receives blood flow via the hepatic artery since an end-to-side portacaval shunt is performed in the donor animal prior to the transplantation, is described. The functional impairment of the receptor liver was done by a ligature of the choledoch, provoking death by sepsis in six of the transplanted animals at 8.16 +/- 6.61 days post transplantation. The auxiliary liver never suffered atrophy and prevented jaundice. It can be concluded that this simple surgical technique could be applied to the heterotopic xenotransplantation when the complications inherent in the immunological aggression are eliminated. PMID- 8354607 TI - Living-related liver transplantation in Africa. AB - Liver transplantation is an effective therapy for end stage liver disease. Nevertheless in many areas of the world organ availability remains a major problem. We report here the success of the first living-related liver transplantation in Africa. The left lateral lobe of the mother was transplanted orthotopically to her 6 year old child suffering from liver cirrhosis complicating glycogen storage disease. The social and medical problems encountered are discussed. Living-related liver transplantation is a viable option in countries where cadaveric organ donation is either illegal or socially unacceptable. PMID- 8354608 TI - Definitive surgical treatment of cholelithiasis in selective patients with liver cirrhosis. AB - A review of 132 cirrhotic patients with cholelithiasis was carried out. Of the 87 patients who underwent definitive surgical procedures for gallstones, patients of Child's A grade had less operative blood loss, blood transfusion and shorter hospital stay than those of B and C grades. No mortality in cirrhotic patients with Child's A and B grade was found in both emergency and elective surgery. Emergency operation in patients with Child's C grade resulted in more operative blood loss and requirement than elective surgery. Patients in this grade had also a higher morbidity rate and four deaths ensued. Of the 83 survivals after definitive procedures, 78 patients (93.9%) were still alive in the following 62.8 months without any biliary tract symptoms. Of patients who survived after cholecystolithotomy, 6 patients (33.3%) had recurrent stones in the same follow up period. Therefore, we recommend that definitive biliary surgery be selectively carried out in cirrhotic patients in Child's A and B grade. However, a conservative approach is more suitable in Child's C patients in emergency conditions and definitive procedures should be considered when their liver function improves. PMID- 8354609 TI - A comparison of laser and cold knife conization. AB - Currently, there are two methods of cervical conization, the laser and the cold knife. This retrospective review examined 217 laser cases and 205 cold knife cases to see which method was superior. The cold knife was shown to have a shorter operative time and a lower overall cost to the patient; however, it was associated with more intraoperative blood loss and more overnight admissions for observation. There were no differences in post operative bleeding complications requiring a visit to the emergency room or to the operating room. It is concluded that overall, there is no clearly superior method of conization for the treatment of cervical intra-epithelial neoplasia. PMID- 8354610 TI - Is cervical cancer in Ethiopian women the result of a sexually transmitted disease? AB - Cervical cancer is the most prevalent cancer of women in Ethiopia and sexually transmitted diseases are highly prevalent in the country. In order to establish a possible cause and effect relationship between sexually transmitted diseases and cervical cancer, likely etiological socio-economic factors for these two conditions have been analysed. While residence, income, age at first coitus, age, number of sexual partners, marital status/profession and duration of sexual life affect both conditions, there is a significant difference between the most important factors in the etiology of the separate conditions. Serological testing shows a high prevalence of gonorrhea, which was used as a marker of STD. Women with gonococcal antibodies had evidence of increased exposure to other STD; there was no such correlation for cervical cancer. Our results indicate that STD per se is unlikely to be a primary cause of CC in Ethiopia. It appears probable that the etiology of CC in Ethiopia is multifactorial. Early exposure of the immature cervical epithelium to STD, the trauma of repeated childbirth, and multiple sexual partners in women whose defence factors are impaired by chronic malnutrition, add up to a major medico-socio-economic factor. The evidence presented here suggests that CC in Ethiopia is not so much the result of a sexually transmitted disease, but a sociosexual disease. PMID- 8354611 TI - Curative local excision for mucosal esophageal carcinoma. AB - We performed a curative local excision for mucosal esophageal carcinoma through a thoracotomy with the help of intraoperative endoscopy and Lugol's staining. The mucosa and submucosa containing the lesion is completely resected, with neither narrowing nor shortening of the esophagus left remaining. PMID- 8354612 TI - A new incision for pyloromyotomy. AB - Over the past two years forty infants with hypertrophic pyloric stenosis have been operated on using a supraumbilical transverse midline skin incision with retraction of the two rectus muscles apart. This incision has given us good exposure, has improved the delivery of the pylorus, produced a strong closure, and given a good cosmetic result. We propose this incision as an alternative to be used in the operative approach to the pylorus in the treatment of hypertrophic pyloric stenosis. PMID- 8354613 TI - Colostomy isolation during abdominal surgery. AB - Isolation of a colostomy during other abdominal operations could become burdensome or lead to contamination of operative site with feces. I present an effective, rapid, and safe technique that involves the placement of a purse string suture and colostomy packing in addition to external dressing. PMID- 8354614 TI - Spontaneous and time-related degeneration of Carpentier-Edwards bioprosthesis in mitral position. AB - To assess the spontaneous and time-related degeneration of the Carpentier-Edwards (C-E) bioprosthesis at 13 years after implantation, the cases of 48 patients who had undergone mitral valve replacement with C-E bioprosthesis are examined. The time-related clinical findings were started from a new rumbling murmur at an average of 5.9 years. The time-related change of transmitral flow was assessed by pressure half time and peak pressure gradient on pulsed Doppler cardiography, and pressure gradient and effective mitral valve area on cardiac catheterization. These values were expressed as an identical linearized curve: pressure half time Y = 13.3 X +41.9, peak pressure gradient Y = 1.47 X +1.25, pressure gradient Y = 1.90 X -3.79, mitral valve area Y = -0.87 X +1.39. From the combined evidence presented by these results, the initial structural deterioration of C-E bioprosthesis is stenotic change of the cusp, not tear or laceration, and correlates well in length of implantation, as evidenced by a linear curve. We are encouraged that the lack of catastrophic prosthetic valve failure, as has been associated with the pericardial valve, affords the opportunity for an elective safe reoperation. PMID- 8354615 TI - Ligation of hernial sac. A needless step in adult hernioplasty. AB - High ligation of indirect hernia sacs in adults is still commonly practiced. Animal and clinical studies have shown that this is unnecessary. To previous studies we add our own experience of over 6,321 adult hernia repairs in which the sacs were rarely excised and never ligated. The questionable logic leading to high ligation is outlined. Experience reveals that non-ligation of indirect sacs is harmless and may decrease post-operative pain. PMID- 8354616 TI - Retroperitoneal lymph node dissection for testicular tumors using the thoracoabdominal approach. AB - During the past 4 years, 16 patients with testicular tumor underwent retroperitoneal lymph node dissection using the thoracoabdominal extraperitoneal approach described by Scardino. In 4 of them, the lymph node dissection was performed without pleurotomy using our modified technique. No uncontrollable intra- or post-complications or operative deaths occurred in our series. From our experience, it was concluded that the thoracoabdominal approach was suitable for maximum exposure of the retroperitoneal area and was associated with lower mobility. Furthermore, our modified extrapleural extraperitoneal technique also provided an excellent operative field comparable to the thoracoabdominal approach. PMID- 8354617 TI - Polytetrafluoroethylene injection for the treatment of partial fecal incontinence. AB - Perianal injection of polytetrafluoroethylene (Teflon or Polytef) paste was used in the treatment of 11 patients with partial fecal incontinence which followed internal sphincterotomy in 7 patients and was idiopathic in 4. All patients had been incontinent for more than 4 years, and had failed to respond to conservative measures. 5 ml of Polytef paste were injected, without anesthesia, in the rectal neck submucosa, above the pectinate line at each of the 3 and 9 o'clock positions. Patients were followed for 18 to 24 months. They were categorized into 3 scores: 1, cured; 2, improved, and 3, no change. Long-term cure (score 1) occurred in 45.4% after the 1st injection and in 63.6% after the 2nd injection. 36.4% showed partial improvement (score 2). No failures occurred. Improvement is believed to be due to the increase in rectal neck pressure produced by the cushion-effect of the polytef submucosal injection. The technique is simple, easy and without complications. It is performed on an outpatient basis. PMID- 8354618 TI - Is the preferential use of polytetrafluoroethylene grafts for below-knee femoropopliteal bypass justified? AB - The usefulness of polytetrafluoroethylene graft (PTFE) for primary below-knee femoropopliteal bypass was examined. Forty-five primary femoropopliteal bypasses with PTFE were performed in 35 patients during a 7-year period. Patients were divided into two groups: above-knee (A-K group, n = 20) and below-knee (B-K group, n = 25) bypass. Differences in intergroup patient demographics were not significant. The primary patency rate in the A-K group at 3 and 5 years was 83.6% and 50.2%, respectively, and was 76.2% at both 3 and 5 years in the B-K group. These differences were not significant. Cause of graft failure, 3 grafts in the A K group and 5 grafts in the B-K group, was kinking or thrombus formation associated with intimal hyperplasia at the distal anastomosis. All grafts in the A-K group with more than 10% stenosis in the early postoperative period had more than 50% stenosis in the late postoperative period. On the other hand, the one graft in the B-K group with 25% stenosis in the early postoperative period had 50% stenosis in the late postoperative period. We concluded that the use of PTFE for primary below-knee femoropopliteal artery is reasonable when atherosclerosis in the proximal popliteal artery is slight. However, close follow-up is necessary to detect and treat graft stenosis early. PMID- 8354619 TI - The diagnosis of internal mammary node metastases of breast cancer. AB - It is important to know the status of internal mammary lymph node (IMN) in estimating the prognosis in patients with breast cancer and/or planning the treatment. In the first series of this study, the diagnostic value of internal mammary lymphoscintigraphy (IMLS) and that of parasternal sonography (PS) were evaluated in 57 patients. The overall diagnostic accuracy of IMLS was 72% and that of PS, 84%, compared with IMN metastases confirmed on a biopsy. In the second series, 23 patients who underwent extended radical mastectomy and were found to have IMN metastases, were examined for the sizes and locations of metastatic IMN. Minute metastatic lymph nodes not detectable by IMLS or PS were found in 9 (39%) of the patients. However, the incidence of metastases to the first and/or second intercostal spaces was 97% for the patients. We concluded that a biopsy of the first and second intercostal spaces is useful in providing the information of IMN status. PMID- 8354620 TI - The role of tamoxifen in the prevention and treatment of benign and malignant breast lesions: a chemopreventive. AB - Tamoxifen (Nolvadex) has been in use for over 20 years and currently is probably the most prescribed anti-cancer medication in the world. It is an orally effective, synthetic, non-steroidal, estrogen antagonist and agonist agent. In studies and trials it has been shown to have only limited side effects. It has produced regressions in women with fibrocystic changes, including precancerous ones, and in those with metastatic breast cancer, where its benefits were first observed. It has increased disease free survival (DFS) and overall survival (OS) rates when given as an adjuvant systemic type of therapy in women with early breast cancers, and it has reduced the incidence of contralateral breast cancers. In addition there are reports indicating its long term use, especially in postmenopausal women, may produce overall health benefits. Over the years an increasing body of data has emerged allowing for viable hypotheses about the possible use of tamoxifen in the prophylaxis of breast cancer, namely that when administered in long-term therapy it may reduce the incidence of breast cancer in women so treated, that it may provide overall health benefits, particularly in postmenopausal women, and that its benefits should far outweigh any risks from its relatively limited side effects. However, carefully designed and conducted clinical trials are needed to test the safety of tamoxifen and its ability to prevent breast cancer before it is advocated for the prophylactic treatment of healthy women to prevent breast cancer, even realizing the increasing magnitude of the breast cancer problem. PMID- 8354621 TI - Risk factors associated with postoperative mortality in patients with esophageal cancer. AB - We examined how impaired host defense mechanisms contribute to fatal complications following transthoracic esophagectomy for malignancy, and compared them with other risk factors. Risks associated with operative mortality were categorized into 5 groups. Twelve of 80 patients had postoperative fatal complications. Five variables in the category of impaired defense mechanisms predicted fatal complications with an accuracy of 86.3%. The accuracy of prediction by preoperative vital organ dysfunction, other preoperative risks, intraoperative risks, and perioperative risks was 87.3%, 90.0%, 87.5%, and 85.0%, respectively. When the 5 groups of risk variables were considered together, the accuracy increased to 93.8%. We conclude that impaired defense mechanisms are one of the important risk factors that contribute to postoperative fatal complications and should be considered with other risk factors when predicting mortality of transthoracic esophagetcomy. PMID- 8354622 TI - Postoperative complications in the treatment of chagasic megaesophagus. AB - The postoperative complications of Chagasic megaesophagus were studied in 250 Chagasic patients referred to the Gastroenterology Clinic of Hospital das Clinicas, Federal University of Minas Gerais, Belo Horizonte, Brazil. The treatment was balloon dilatation in 45 (18.0%), myotomy and cardioplasty in 63 (25.2%), Merendino's surgery in 139 (55.6%), esophagogastroplasty in 2 (0.8%) and esophagocoloplasty in 1 (0.4%). There were 125 (50%) early and 30 (12%) late postoperative complications, and in 65 patients (26%) recurrent dysphagia was noted: nineteen (7.6%) after myotomy and cardioplasty, 9 (3.6%) after Merendino's operation and 37 (14.8%) after balloon dilatation. Eighty-five patients (34%) needed reoperations either to correct recurrent dysphagia (56 patients, 22.4%) or to treat other complications (29 patients, 11.6%). The reoperations to correct the 19 recurrences after myotomy and cardioplasty were Merendino's operation (12 patients, 4.8%), forceful dilatation (1 patient, 0.4%), forceful dilatation followed by Merendino's (2 patients, 0.8%), another myotomy (2 patients, 0.8%), myotomy followed by Merendino and balloon dilatation (1 patient, 0.4%) or esophagogastroplasty (1 patient, 0.4%). The recurrences after dilatation were treated by myotomy (15 cases, 6%), Merendino's operation (12 cases, 4.8%) and myotomy followed by Merendino's (3 cases, 1.2%). After Merendino seven reoperations (2.8%) were done: reduction of interposed loop (6 cases, 2.4%) and esophagocoloplasty (1 case, 0.4%). The time elapsed between the first operation and reoperation or dilatation varied from a few weeks to 18 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354623 TI - Anencephaly--organ transplantation? PMID- 8354624 TI - The brain stem in brain death: a critical review. PMID- 8354625 TI - When is medical treatment "futile"? PMID- 8354626 TI - The impact of assisted suicide on persons with disabilities--is it a right without freedom? PMID- 8354627 TI - In re T.A.C.P. PMID- 8354628 TI - In re Ray. PMID- 8354629 TI - Paternalism, disability, and the right to die. PMID- 8354630 TI - Carlton Johnson, et al., v. Webb Thompson, M.D., et al. Petition for a Writ of Certiorari to the United States Court of Appeals for the Tenth Circuit. PMID- 8354631 TI - Effects of frontal lesions on a selective attention task. AB - We set out to test the hypothesis that patients with frontal damage are specifically disabled in carrying out tasks requiring a high level of controlled attention. A group of patients with frontal lesions and another group of patients with retrorolandic lesions were tested for selective attention on a computerized task designed to produce a conflict situation between automatic and controlled processes. Frontal patients proved to be significantly more prone to errors of commission (false alarms) than retrorolandic patients. PMID- 8354632 TI - Botulinum toxin treatment in patients with focal dystonia and hemifacial spasm. A multicenter study of the Italian Movement Disorder Group. AB - In six Centers belonging to the Italian Movement Disorder Study Group, the efficacy of botulinum toxin treatment was evaluated in an open collaborative study in 251 patients with focal dystonia and hemifacial spasm. The percentage of functional improvement ranged from 66% to 81% in patients with blepharospasm, from 40% to 51% in patients with spasmodic torticollis and from 73% to 81% in those with hemifacial spasm. Good results were also obtained in patients with oromandibular dystonia, laryngeal dystonia and writer's cramp. Side effects were mild and transient. Local botulinum toxin injection is the first choice symptomatic treatment in focal dystonia and hemifacial spasm. PMID- 8354634 TI - Chromosome 22 monosomy in a radiation-induced meningioma. AB - We report for the first time on the cytogenetics of a radiation-induced meningioma, in a patient without neurofibromatosis. Chromosome 22 monosomy was found in more than 50% of the cells examined. These findings seem to suggest that the same kind of chromosomal aberrations are found in both "idiopathic" and radiation-induced meningiomas and that a common etiopathogenetic mechanism might be at work in meningiomas of whatever origin. PMID- 8354633 TI - Myopathy in long-term AZT therapy: clinical, electrophysiological and biopsy study in 67 HIV+ subjects. AB - The occurrence of muscular pathologies in AZT treated subjects has been evaluated in 67 HIV seropositive outpatients (56 AZT-treated and 11 untreated controls) in a neurological clinical and paraclinical follow-up study. Standard electromyographic and electrodiagnostic examinations, together with muscle enzyme determination, were performed in every subject, and periodically repeated at fixed intervals; in 11 patients a muscle biopsy sample was also obtained. An AZT related myopathy was diagnosed in 8 biopsied cases; 9 more patients were considered to have AZT myopathy on clinical, EMG and ex juvantibus criteria. Statistical analysis showed that treatment duration was more relevant to the development of the myopathy than AZT dosage, though an individual predisposition could not be excluded, at least in a small number of cases. The risk of developing a toxic myopathy will therefore have to be considered when evaluating long-term effects of AZT therapy. PMID- 8354635 TI - Focal inhibitory seizures as the presenting sign of ischemic cerebrovascular disease. AB - Recurrent episodes of transient neurological dysfunction occurring in a patient with evidence of recent multiple lacunar infarctions were at first diagnosed as transient ischemic attacks (TIAs), but later proved to be due to focal inhibitory seizures. The differential diagnosis between TIAs and partial epileptic seizures in patients with ischemic cerebrovascular disease may sometimes be difficult in the presence of uncommon clinical manifestations. PMID- 8354637 TI - Tarsal tunnel syndrome in skiers. Case report. AB - We describe a case of tarsal tunnel syndrome recently observed in a skier. It is the second case to be reported. Our aim is to stress the relevance of this syndrome to foot pain in these athletes. PMID- 8354636 TI - Unusual seizures with a benign course in a case of acute lymphoblastic leukemia of childhood. AB - We report the unusual seizures in a patient with acute lymphoblastic leukemia. The convulsive disorder began acutely as partial somatomotor status epilepticus and with diffuse EEG slowing. The seizures then became myoclonic-atonic (drop attacks) and an EEG focus appeared on the left paramedian centro-parietal areas, activated by proprioceptive stimuli. Despite the severity of the clinical picture at onset, the seizures showed a benign course, and disappeared on carbamazepine therapy. We think that this epileptic syndrome may have been caused by diffuse iatrogenic encephalopathy, probably related to intrathecal methotrexate therapy. PMID- 8354638 TI - Interferon-gamma reduces tumor-induced Ia- macrophage-mediated suppression: role of prostaglandin E2, Ia, and tumor necrosis factor-alpha. AB - Tumor growth enhances macrophage (M phi) suppressor activity by causing M phi to increase synthesis of inhibitory molecules such as prostaglandin E2 (PGE2) or decreasing their expression of up-regulatory molecules such as the class II MHC protein Ia. Although these tumor-induced changes are correlated, it is unknown whether tumor-bearing host (TBH) Ia- M phi become more suppressive by increasing their PGE2 synthesis. To assess the role of PGE2 in tumor-induced Ia- M phi mediated suppression of CD4+ T-cell alloreactivity, unseparated (Ia(+)-enriched) or Ia(+)-depleted (Ia-) populations of murine normal host (NH) or TBH splenic M phi were added to mixed lymphocyte reaction (MLR) cultures. NH or TBH Ia- M phi were significantly more suppressive than their respective unseparated populations, and TBH Ia- M phi were more suppressive than their NH counterparts. When PGE2 production was blocked with indomethacin, TBH Ia- M phi-mediated suppression was reduced more than suppression mediated by all other M phi populations. A PGE2-specific ELISA showed more PGE2 in Ia- M phi-containing cultures than in those with whole M phi and more in cultures containing TBH Ia- M phi than in their NH counterparts. Because interferon-gamma (IFN-gamma) is a potent M phi activation molecule that regulates both Ia expression and PGE2 production, the effects of IFN-gamma on tumor-induced Ia- M phi-mediated suppression were investigated. Exogenous IFN-gamma reduced suppression mediated by all M phi populations except NH unseparated M phi. IFN-gamma suppressed alloreactivity without M phi or with NH unseparated M phi. Suppression mediated by NH or TBH Ia-, and TBH unseparated M phi was also reduced when M phi were pre incubated with IFN-gamma before their addition to MLR cultures. IFN-gamma addition did not block Ia- M phi-mediated suppression by decreasing M phi PGE2 production. In fact, IFN-gamma addition increased PGE2 production two-fold in MLR cultures. However, IFN-gamma partly reduced suppression mediated by exogenous PGE2 added to M phi-depleted cultures. Cytofluorometric analysis showed that IFN gamma increased the percentage of Ia+ M phi in NH and TBH Ia- M phi populations. Blocking TNF-alpha activity with anti-TNF-alpha antibodies caused IFN-gamma to suppress alloreactivity in all M phi-added cultures. Collectively, these data show that tumor-induced suppression mediated by Ia- M phi is caused by increased PGE2 synthesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8354639 TI - Pancreas-specific venular labeling by monastral blue B in the BB rat: modulation by prostaglandins and their inhibitors. AB - Leaky blood vessels in the microcirculation can be detected in vivo by injecting an animal with colloidal pigments like Monastral blue B (MbB). We have previously used this labeling method in the BB rat, an animal model of spontaneous autoimmune diabetes, and detected increased vascular permeability restricted to the venules of the pancreas. The earlier data suggested that pancreata of animals susceptible to labeling contain trapped intravascular monocytes that are activated to release vasoactive mediators after phagocytosis of MbB. To explore these observations further, we investigated the effects of prostaglandins on this system. Prostaglandins are known to be important mediators of inflammatory responses and to modulate the expression of disease in other animal models of autoimmunity. We now report that MbB-induced pancreatic labeling is modulated by misoprostol (an analogue of prostaglandin E1), prostaglandins of the E series, and inhibitors of prostaglandin synthesis. The nonsteroidal anti-inflammatory drugs ibuprofen and ketorolac both reduced the intensity of labeling in susceptible BB rats in a dose dependent manner. In contrast, both misoprostol and prostaglandin E2 given at low doses induced pancreatic permeability in the labeling-resistant Wistar Furth rat. To extend this finding, we also tested much higher drug doses, since at high concentrations, E series prostanoids exert anti inflammatory effects. We observed that large doses of prostaglandin E1, prostaglandin E2, and misoprostol all suppressed labeling in the BB rat. We conclude that presence of MbB in the pancreatic circulation of the rat induces organ specific venular leakage by an inflammatory process involving prostaglandins. PMID- 8354640 TI - The effect of ebselen on polymorphonuclear leukocyte and lymphocyte migration to inflammatory reactions in rats. AB - Ebselen, a selinyl organic compound with anti-inflammatory properties was found by us previously to inhibit in vitro human polymorphonuclear leukocyte (PMNL) adhesion to and migration through umbilical vein endothelium monolayers. Here we investigated in rats the effect of ebselen on PMNL and spleen T lymphocyte (SPLT) migration to inflamed joints induced by intra-articular (i.a) injection of recombinant murine tumor necrosis factor alpha (mTNF alpha) and to dermal inflammatory reactions. Inflammation was induced in the carpal and talar joints of rats by intra-articular (i.a.) injection (100 ng) of mTNF alpha once daily for 2 days. Corresponding joints in the opposite limb received diluent. Simultaneously, the rats were treated p.o. with either ebselen (100 mg/kg/day) or indomethacin (2 mg/kg/day) or vehicle for 2 days. Dermal inflammation was induced by intradermal injection (0.05 ml) of inflammatory stimuli. Accumulation of 51Cr labelled rat blood PMNL, 111In-labeled SPLT, and extravasation of 125I-labelled human serum albumin (HSA) in the joints and in skin sites were measured. Treatment of rats with ebselen inhibited by 33-65% PMNL migration to the mTNF alpha inflamed joints, and to dermal inflammation induced by zymosan activated serum (ZAS; containing C5adesArg), endotoxin (LPS), mIL-1 beta and mTNF alpha. Migration of SPLT to dermal inflammation induced by interferon gamma (IFN gamma), poly-inosine-cytosine (poly I:C) and LPS was also significantly inhibited (22 33%), but SPLT migration into the inflamed joints was not effected by ebselen. Indomethacin treatment of rats also inhibited PMNL migration into the inflamed joints, but unlike ebselen, indomethacin inhibited only ZAS induced dermal PMNL accumulation. In contrast to ebselen, indomethacin inhibited SPLT migration into the inflamed joints as well as to the dermal inflammation induced by poly I:C and a delayed-type hypersensitivity reaction (DTH). In addition, treatment of rats with indomethacin significantly inhibited plasma protein (125I-HSA) extravasation in the inflamed joints and the dermal inflammatory reaction induced by ZAS, but ebselen had no such effect. In conclusion, ebselen appears to have a distinct antiinflammatory mechanism of action from indomethacin and the PMNL findings are consistent with a direct inhibitory action on PMNL activation and PMNL transendothelial migration as observed previously in vitro. PMID- 8354641 TI - Inhibition of ornithine decarboxylase activity decreases polyamines and suppresses DNA synthesis in human colonic lamina propria lymphocytes. AB - Ornithine decarboxylase (ODC) and the polyamines are essential for cell proliferation in a variety of cells including lymphocytes. In this study, we investigated the potential role of ODC and polyamines in human colonic lamina propria lymphocytes (LPL) compared to peripheral blood lymphocytes (PBL). Our results show that con A stimulation of LPL and PBL was associated with marked increases in ODC and polyamines. The specific inhibitor of ODC, alpha difluoromethylornithine (DFMO), resulted in a complete inhibition of ODC activity and depletion of putrescine, spermidine and spermine levels. DFMO also suppressed DNA synthesis of LPL and PBL by up to 48% and 62% respectively. This antiproliferative effect was reversed by adding back the polyamines putrescine (1 mM), spermidine (10 microM) or spermine (10 microM) to the culture medium. We conclude that ODC and the polyamines are important for human LPL proliferation, and hence may play a role in human mucosal immune function. PMID- 8354642 TI - In vivo immunopharmacological properties of tuftsin and four analogs. AB - Four analogs of the natural macrophage-activator peptide tuftsin (T-K-P-R) were synthesized with the aim of obtaining compounds more effective in the stimulation of the immune system than tuftsin. Modifications to the parent tuftsin molecule were (i) substitution of the proline (P) residue, and/or (ii) replacement of the N-terminal residue threonine (T). The study presented here shows that the integrity of the NH2 terminus is not mandatory for a full biological tuftsin-like activity. Our data also suggest that the analogue F-(psi)-K-ABO-R, where ABO is a non-natural amino acid, is a promising agent for immunotherapy of infectious and neoplasic diseases for which tuftsin has already demonstrated some efficacy. PMID- 8354643 TI - Glucocorticoids modulate soluble interleukin-2 receptor levels in vivo depending on the state of immune activation and the duration of glucocorticoid exposure. AB - We have studied the modulation of circulating soluble interleukin-2 receptor (sIL 2R) levels by glucocorticoids in subjects with different states of immune activation. In contrast to normal subjects, 40 mg methylprednisolone administration over 6 days resulted in a significant fall of elevated circulating sIL-2R levels (p < 0.05) in patients with active atopic dermatitis, most pronounced in those patients showing the highest pre-treatment levels of sIL-2R and scores of disease activity. Following administration of 1 mg dexamethasone, sIL-2R levels remained unchanged both in normal subjects and patients with atopic dermatitis. Circulating sIL-2R levels were significantly decreased in patients with long-term hypercortisolism due to Cushing's disease (p < 0.05) and significantly elevated (p < 0.05) in hypocortisolemic patients. Blockade of adrenal cortisol secretion by 1.5 g metyrapone did not change sIL-2R levels in normal subjects and sIL-2R levels were not affected in depressive patients, either before or after clinical remission or following 1.5 g metyrapone administration. These data suggest that the effect of glucocorticoid administration on circulating sIL-2R levels depends on the state of immune activation and the duration of glucocorticoid exposure. The circulating sIL-2R levels show significant changes in patients with chronic alterations of endogenous glucocorticoid secretion and in response to prolonged glucocorticoid therapy in disorders with immune activation. PMID- 8354644 TI - Community health development: an anthology of the works of Guy W. Steuart. PMID- 8354645 TI - Social and behavioral change strategies. 1985. PMID- 8354646 TI - Guy W. Steuart: the person and his works. PMID- 8354647 TI - The importance of programme planning. 1959. PMID- 8354648 TI - Community health education. 1962. PMID- 8354649 TI - Community health development: an overview of the works of Guy W. Steuart. PMID- 8354650 TI - Health, behavior, and planned change: an approach to the professional preparation of the health education specialist. 1965. PMID- 8354651 TI - Planning and evaluation in health education. 1969. PMID- 8354652 TI - Scientist and professional: the relations between research and action. 1969. PMID- 8354653 TI - The world is not round: innovation and the medical wheel. 1977. PMID- 8354654 TI - Social and cultural perspectives: community intervention and mental health. 1978. PMID- 8354655 TI - Changing patterns of infections in the immunocompromised patient with cancer. AB - Infectious complications have become frequent causes of morbidity and mortality in cancer patients, often replacing the primary disease as the leading cause of death. Intensive chemotherapy regimens, widespread prophylactic and therapeutic administration of antibiotics, and reliance on intravascular catheters have altered the epidemiology of infections in these patients. The authors review how gram-positive bacteremias have replaced gram-negative bacteremias as the leading causes of infections in many patients with cancer, and how fungal infections have become a leading cause of morbidity and mortality as bacterial infections are better controlled. Multiresistant organisms that have developed during the past decade and future trends in infectious complications of cancer patients are also discussed. PMID- 8354656 TI - Evolving risk factors for infectious complications of cancer therapy. AB - Advances in the supportive care of cancer patients have led to improved long-term outcomes. Infection, however, remains the most significant complication of cancer therapy. The author reviews the impact of new cancer therapies on the risk factors for infectious complications and the impact of therapy on the alterations in host defense. The relative importance of therapy-induced changes are contrasted with immunologic abnormalities associated with specific cancers. In addition, the author contrasts these changes with the infectious complications of human immunodeficiency virus infection, highlighting common themes in immunocompromised patients. PMID- 8354657 TI - Understanding and diagnosing infectious complications in the immunocompromised host. Current issues and trends. AB - The number of patients who are at an increased risk of life-threatening infection has expanded greatly during the past decade. This expansion is because of two events, one terrible in its consequences, the other very positive. The first is the unprecedented epidemic of opportunistic infection that follows infection with the human immunodeficiency virus or the acquired immunodeficiency syndrome. The second is a direct consequence of the successes of the transplant surgeon, the cancer chemotherapist, the hematologist, and the rheumatologist. The authors review the current issues and trends in understanding and diagnosing infectious complications in the immunocompromised host. PMID- 8354658 TI - Infectious complications in the immunocompromised host. The antimicrobial armamentarium. AB - The treatment of infectious complications in the cancer patient has evolved as a consequence of the developments in cancer chemotherapy, which significantly impair immune function. Broad-spectrum, single-agent antibiotics have replaced more cumbersome multidrug regimens for empiric coverage of fever and neutropenia in many institutions. The use of new, potent oral antibiotics may be a next step toward further simplifications. Several new antivirals have come into clinical use in the past decade, and reports of viral resistance to the standard agent, acyclovir, have come forth. Increasing experience with new (and older) antifungal and antiparasitic agents has given a better understanding of the use of these drugs for both prophylaxis and treatment. This overview includes a critical appraisal of the attributes and limitations of current antibiotics, antivirals, antifungals, and antiparasitic agents for the immunocompromised host. PMID- 8354659 TI - Approach to management of fever and infection in patients with primary bone marrow failure and hemoglobinopathies. AB - The characteristic spectrum of infections in patients with aplastic anemia, chronic neutropenic diseases, sickle cell disease, thalassemia, and other hemoglobinopathies are described. The major risk factor for infection in patients with bone marrow failure is the degree of neutropenia and monocytopenia. In patients with aplastic anemia, invasive fungal infections emerge as the major causes of mortality. Life-threatening infections are rare in patients with chronic neutropenic diseases; however, necrotizing enterocolitis due to Clostridium species may be an exception. Bacterial infections, predominantly with encapsulated bacteria, are the most common cause of death in patients with sickle cell disease, especially those who are younger than 5 years of age. Patients with thalassemia and other hemoglobinopathies are particularly susceptible to life threatening infections with Yersinia enterocolitica as a result of iron overload or of the chelating therapy with desferrioxamine. PMID- 8354660 TI - Approach to the immunocompromised host with pulmonary symptoms. AB - Respiratory disease is common in patients who are immunocompromised, which may be because of opportunistic infection, non-infectious processes related to the underlying disease, or therapy instituted for treatment. Approaching pulmonary symptoms in an immunocompromised host is a complex challenge because the symptoms represent a diverse spectrum of disease. In addition to the routine clinical evaluation, this article reviews four diagnostic procedures to characterize pulmonary disease. Current concepts regarding the prevention of infection are also addressed. PMID- 8354661 TI - Growth of mycoplasma transformed tTN129 cells depends on IGF-I. PMID- 8354662 TI - Staurosporine induces multinucleation following chromosome decondensation in Colcemid-arrested cells. PMID- 8354663 TI - A better defined medium for human prostate cancer cells. PMID- 8354664 TI - A simplified in vitro model of oxidant injury using vascular endothelial cells. AB - Oxidant injury of the vascular endothelium is considered an early event in the pathogenesis of atherosclerosis. The model of oxidant injury is crucial to the investigation of antioxidants. In the present study, a convenient in vitro model of oxidant injury induced by hydrogen peroxide (H2O2) was developed using bovine pulmonary artery endothelial cells (PAEC). Viability of PAEC grown in 96-well culture plates was determined with methylthiazol tetrazolium (MTT) colorimetric assay. Cell membrane integrity was measured by lactate dehydrogenase (LDH) release from PAEC grown in 24-well plates. Malondialdehyde (MDA, a product of lipid peroxidation) in PAEC grown in 6-well plates was detected by a thiobarbituric acid fluorometric assay. Incubation of H2O2 with PAEC caused a dose-dependent decrease of cell viability, an increase of LDH release, and an elevation of MDA production. MTT assay was convenient, quantitative, non radioactive, and suitable for testing a large number of samples. The fluorometric assay for measuring MDA production in endothelial cells used 6-well plates instead of 80-cm2 flasks employed by previous investigators. The use of multiwell culture plates in these assays made it possible for more samples to be tested in any single experiment. The three assays are reproducible with low intraplate and interplate coefficients of variation. This in vitro model is suitable for screening antioxidants and for studying pharmacodynamics at the cellular level. PMID- 8354665 TI - Culturing the epiblast cells of the pig blastocyst. AB - Pig epiblast cells that had been separated from other early embryonic cells were cultured in vitro. A three-step dissection protocol was used to isolate the epiblast from trophectoderm and primitive endoderm before culturing. Blastocysts collected at 7 to 8 days postestrus were immunodissected to obtain the inner cell mass (ICM) and destroy trophectodermal cells. The ICM was cultured for 2 to 3 days on STO feeder cells. The epiblast was then physically dissected free of associated primitive endoderm. Epiblast-derived cells, grown on STO feeders, produced colonies of small cells resembling mouse embryonic stem cells. This primary cell morphology changed as the colonies grew and evolved into three distinct colony types (endodermlike, neural rosette, or complex). Cell cultures derived from these three colony types spontaneously differentiated into numerous specialized cell types in STO co-culture. These included fibroblasts, endodermlike cells, neuronlike cells, pigmented cells, adipogenic cells, contracting muscle cells, dome-forming epithelium, ciliated epithelium, tubule forming epithelium, and a round amoeboid cell type resembling a plasmacyte after Wright staining. The neuronlike cells, contracting muscle cells, and tubule forming epithelium had normal karyotypes and displayed finite or undefined life spans upon long-term STO co-culture. The dome-forming epithelium had an indefinite life span in STO co-culture and also retained a normal karyotype. These results demonstrate the in vitro pluripotency of pig epiblast cells and indicate the epiblast can be a source for deriving various specialized cell cultures or cell lines. PMID- 8354666 TI - Morphogenesis of "duct-like" structures in three-dimensional cultures of human cancerous pancreatic duct cells (Capan-1). AB - Pancreatic duct cells secrete water and ions, bicarbonate in particular. The study of these secretion processes is hindered by the unavailability of human pancreatic tissue. In this study, pancreatic human cells of the Capan-1 cell line were employed to investigate secretion in vitro. These cells are of ductal origin because in standard culture they polarize spontaneously forming domes in the culture dishes, indicating the existence of transepithelial exchange of water and electrolytes. In culture in suspension, Capan-1 cells form hollow spheroids bounded by a cell monolayer in a radial organization. These three-dimensional structures could be maintained in culture for more than 140 days. In young cultures, the cells of these spheroids grew rapidly (mitotic index = 9.2% on Day 2). Their cytologic features were analyzed by immunocytochemical, cytoenzymatic methods, and by electron microscopy. We showed that they are: a) polarized with an apical pole facing the culture medium; b) organized in a monolayer; c) bound by tight junctions and desmosomes; d) characterized by a particular distribution of enzyme systems known to play a role in ion exchanges, with placental-type alkaline phosphatases and carbonic anhydrases IV on their apical membranes and Ca(2+)-ATPases on their basolateral membranes. Crystalline structures were detected histochemically in the closed cavities and in the intercellular spaces of the spheroids. X-ray emission spectroscopy and electron diffraction showed that they consisted of calcium phosphate in an apatite structure. They were assumed to derive from a raised concentration of Ca2+ and phosphate ions under the impermeable monolayer of the spheroids. In addition, numerous cells secreted M1 gastric-type mucins, and acquired the ability to produce colonic-type M3 mucins. These hollow spheroids swelled during the culture period. Taken together these results suggest that the Capan-1 cells organized in these hollow spheroids exchange ions. Their three-dimensional structure resembles that of human pancreatic ducts, and they may therefore represent a useful model system for investigation of Cl- and HCO3- ion exchange processes in the human pancreas. PMID- 8354667 TI - Role of thrombospondin in the adhesion of human endothelial cells in primary culture. AB - The role of thrombospondin on the adhesion of endothelial cells in primary culture was studied using a serum-free defined medium or thrombospondin-depleted fetal bovine serum. Under these conditions, only 6% of the cells adhered to gelatin-coated dishes, whereas cells adhering to gelatin in the presence of normal fetal bovine serum were considered as 100% adhesion. The percentage of cells attached to fibronectin or thrombospondin-coated dishes in thrombospondin depleted serum was 66 and 32%, respectively. The addition of purified platelet thrombospondin to thrombospondin-depleted serum increased the adhesion of endothelial cells to gelatin and to thrombospondin, up to 32 and 59%, respectively, and restored the attachment to fibronectin to the same extent as that observed in the presence of normal serum. In contrast to the attachment, the spreading of the adhering cells was not further influenced by the addition of soluble thrombospondin. Subcultured cells did not require any protein for adhering to gelatin substrata. These observations indicate that thrombospondin plays a major role in the adhesion of endothelial cells in primary culture. PMID- 8354668 TI - Development of primary culture of ovine fetal hepatocytes for studies of amino acid metabolism and insulinlike growth factors. AB - We report the development and characterization of a system of primary culture of ovine fetal hepatocytes to aid in the understanding of the cellular regulation of fetal growth and metabolism with emphasis on amino acid metabolism and insulinlike growth factor gene expression and to allow comparison to in vivo studies. Hepatocytes were isolated from late gestation fetal lambs by in situ perfusion and collagenase digestion utilizing occlusion of the ductus venosus to limit intrahepatic shunting. Hepatocytes were cultured in media modified to mimic fetal concentrations of glucose, lactate, and amino acids. Ovine fetal hepatocytes in primary culture maintain the pattern of fetal amino acid production and utilization seen across the fetal liver in vivo. Specifically, there is a net production of serine and a net utilization of glycine. Cultured ovine fetal hepatocytes specifically increase tritiated thymidine incorporation in response to insulin and insulinlike growth factor II (IGF-II). IGF-II mRNA abundance is high and IGF-I mRNA is low in cultured ovine fetal hepatocytes as in the fetal sheep liver in vivo. These data demonstrate the successful isolation of ovine fetal hepatocytes that retain some of the characteristics of the ovine fetal liver while maintained in short-term culture. PMID- 8354669 TI - Notice of retraction. PMID- 8354670 TI - Intertrochanteric osteotomy and autogenous bone-grafting for avascular necrosis of the femoral head. AB - A prospective study was done of forty-five hips in forty-three patients who had Ficat stage-III avascular necrosis of the anterosuperior part of the femoral head. The patients had been followed for an average of sixty-five months (range, thirty-six to 126 months) after an operation that included a valgus-flexion intertrochanteric osteotomy, curettage of necrotic bone, and grafting of autogenous bone to the avascular segment. The patients were 32 +/- 8 years old (mean and standard deviation). Patients who were more than forty-five years old, had an underlying systemic disease, had been treated with steroids, had more extensive involvement of the femoral head, or were poorly motivated were excluded from the study. The mean preoperative Harris hip score was 34 +/- 10 points, and the mean score at the most recent assessment was 90 +/- 7 points. Six hips (13 per cent) failed; failure was defined as a Harris hip score of less than 70 points or the performance of a subsequent replacement arthroplasty. Survivorship analysis demonstrated cumulative survival without such failure to be 87 per cent at five years; the ten-year cumulative survival was essentially unchanged. The results of this study suggest that the role of intertrochanteric osteotomy and bone-grafting of the femoral head should be considered anew for the treatment of avascular necrosis of the hip in younger patients who have not received steroids. The results of this procedure should be compared again with those of arthroplasty in the treatment of this condition. PMID- 8354671 TI - Acute slipped capital femoral epiphysis: the importance of physeal stability. AB - To test the traditional classification system of slipped capital femoral epiphysis, we evaluated the presenting symptoms and radiographs of fifty-four patients and reclassified the slipped epiphyses as unstable or stable, rather than acute, chronic, or acute-on-chronic. Slips were considered to be unstable when the patient had such severe pain that weight-bearing was not possible even with crutches. Slips were considered to be stable when the patient could bear weight, with or without crutches. We reviewed the records on fifty-five hips in which the slip would have been classified as acute because the duration of symptoms was less than three weeks; thirty of these were unstable and twenty-five were stable. All slips were treated with internal fixation. A reduction occurred in twenty-six of the unstable hips and in two of the stable hips. Fourteen (47 per cent) of the thirty unstable hips and twenty-four (96 per cent) of the twenty five stable hips had a satisfactory result. Avascular necrosis developed in fourteen (47 per cent) of the unstable hips and in none of the stable hips. We were not able to demonstrate an association between early reduction and the development of avascular necrosis. PMID- 8354672 TI - The epidemiology of bilateral slipped capital femoral epiphysis. A study of children in Michigan. AB - The records of 224 children who had a slipped capital femoral epiphysis and who had no underlying metabolic or endocrine disorder were studied retrospectively to investigate the epidemiology of bilateral slipped capital femoral epiphysis. Eighty-two (37 per cent) of the 224 children (fifty-one boys and thirty-one girls) had a bilateral slip. Sixty-four of these children were black and eighteen were white. The age at the time of the diagnosis of the first slip was 13 +/- 1.7 years (mean and standard deviation), the duration of the symptoms was 5 +/- 5.0 months, and the angle of the slip was 26 +/- 16 degrees. Obese children were younger at the time of the diagnosis of the first slip (12 +/- 1.6 compared with 13 +/- 1.6 years for the children who were not obese, p = 0.001). The diagnosis of a slipped capital femoral epiphysis was made simultaneously in both hips in forty-one children and sequentially in forty-one children. Compared with the children in whom both hips were diagnosed simultaneously, the children in whom the hips were diagnosed sequentially had had a shorter duration of the symptoms before the diagnosis of the first slip (3 +/- 2.4 compared with 7 +/- 5.9 months, p = 0.0003), were younger at the time of the diagnosis of the first slip (12 +/- 1.9 compared with 13 +/- 1.2 years, p = 0.001), and tended to be more obese (p = 0.025). In 88 per cent of the patients who had sequential slips, the second slip was diagnosed within eighteen months after the diagnosis of the first slip.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354673 TI - Complications of use of the Ilizarov technique in the correction of limb deformities in children. AB - We reviewed the records of the first forty patients who had been managed at our institution with the Ilizarov technique for the correction of limb deformities, including limb-length inequality, to delineate the complications of this method of treatment. The duration of follow-up ranged from two and one-half to four years. A complication was defined as any untoward occurrence to a patient either during the course of treatment or after removal of the fixator. A major complication was considered one that necessitated an additional operative procedure; caused lasting sequelae, such as malunion, deformation of new bone, joint contracture or stiffness, or nerve palsy; or prolonged the treatment. A minor complication was regarded as one that responded to non-operative treatment and did not cause lasting sequelae, such as transient decreased motion of the joint, paresthesia, or pin-track infection. There were eighty-eight complications -thirty-eight, major, and the remaining fifty, minor--in the sixty-one segments of the limb that were treated; this represented an average of almost one and one half complications for each segment. Twenty-nine unplanned operative procedures were performed either during treatment with the Ilizarov technique or after removal of the fixator. As anticipated, the prevalence of major complications was highest in the patients who had had more complex and prolonged treatment. Such complications were encountered less often as the surgeons gained experience with the procedure, but the rate of minor complications remained relatively constant, despite the increased experience.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354674 TI - Injury of the sciatic nerve associated with acetabular fracture. AB - In order to document functional outcome, we followed fourteen patients who had an injury of the sciatic nerve associated with a displaced acetabular fracture for a mean of twenty-seven months. In three of the patients, the injury was iatrogenic. Electromyography was useful in the localization and determination of the severity of the injury. According to the functional scale that was used, all but one patient had a satisfactory (fair or better) functional outcome, but eleven patients had residual neurological sequelae that ranged from minor paresthesia to footdrop. Seven patients who had an injury of both the tibial and peroneal divisions of the sciatic nerve had complete or nearly complete motor and sensory recovery of the tibial component. The patients who had isolated, mild involvement of the peroneal nerve had a favorable prognosis, but those who had a severe injury of the peroneal component, whether it was isolated or associated with an injury of the tibial component, did not recover good function. PMID- 8354675 TI - Arthroscopically assisted arthrodesis for osteoarthrotic ankles. AB - Arthroscopically assisted arthrodesis of the ankle was performed in nineteen patients who were selected because they had osteoarthrosis with minimum or no deformity of the ankle. After arthroscopic resection of the synovial membrane, the subchondral bone, and cartilage from the tibial, fibular, and talar articular surfaces, three percutaneous, cannulated, cancellous screws were used for internal fixation. Of these nineteen patients, ten had radiographic evidence of union by the second postoperative month; five, by the third; one, by the fifth; and one, by the sixth. Two patients had a non-union, but a successful open arthrodesis was subsequently performed on one of these patients. At two years, the scoring system of Mazur et al. indicated a poor result in one patient (after a non-union), a fair result in two, a good result in four, and an excellent result in twelve patients. Arthroscopically assisted arthrodesis of the ankle produces good results in patients who have osteoarthrosis of the ankle with minimum or no deformity, and the immediate postoperative morbidity is of very short duration. PMID- 8354676 TI - Hypoplasia of the glenoid. A review of sixteen patients. AB - We reviewed the records of sixteen patients, fifteen to sixty-two years old, who had glenoid hypoplasia with or without an associated deformity of the humeral head. The patients were divided into three groups: those who had bilateral glenoid hypoplasia without instability of the shoulder (Group I), those who had bilateral glenoid hypoplasia with instability of the shoulder (Group II), and those who had unilateral glenoid hypoplasia with deformity of the humeral head (Group III). When first seen by us, thirteen of the sixteen patients had pain in the shoulder, which they had noted after an increase in their previous level of activity. All were managed with a specific rehabilitation program for the shoulder. The patients were followed for an average of five years, and most were able to return to their previous level of activity with the resolution of the symptoms. PMID- 8354677 TI - Loss of external rotation following anterior capsulorrhaphy of the shoulder. AB - A retrospective study was performed on twenty shoulders in nineteen patients who had been managed for severe loss of external rotation of the glenohumeral joint after a previous anterior capsulorrhaphy for recurrent instability. All patients had noted a restricted range of motion, and seventeen shoulders had been painful. In seven shoulders, the humeral head had been subluxated or dislocated posteriorly, and sixteen shoulders had been affected by mild to severe glenohumeral osteoarthrosis. All twenty shoulders were treated with a reoperation, which consisted of a release of the anterior soft tissue. In addition, eight shoulders had a total arthroplasty and one had a hemiarthroplasty. At an average duration of follow-up of forty-eight months, all shoulders had an improvement in the ratings for pain and range of motion. The average increase in external rotation was 45 degrees (range, 25 to 65 degrees). Patients who have a major loss of external rotation following anterior capsulorrhaphy of the shoulder may be at risk for the development of posterior subluxation and glenohumeral osteoarthrosis. The performance of an anterior release should be considered for these patients. PMID- 8354678 TI - Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure. AB - Tensile testing to failure was done on 235 cortical specimens that had been machined from forty-seven femora from human cadavera. The donors had ranged in age from twenty to 102 years at the time of death. After mechanical testing, the porosity, mineralization, and microstructure were determined. Linear regression analysis showed that the mechanical properties deteriorated markedly with age. Ultimate stress, ultimate strain, and energy absorption decreased by 5, 9, and 12 per cent per decade, respectively. The porosity of bone increased significantly with age, while the mineral content was not affected. Microstructural analysis demonstrated that the amount of haversian bone increased with age. Both bivariate and multivariate analyses demonstrated the importance of age-related changes in porosity to the decline in mechanical properties. Changes in porosity accounted for 76 per cent of the reduction in strength. Microstructural changes were highly correlated with porosity and therefore had little independent effect. Mineral content did not play a major role. Thus, the quantitative changes in aging bone tissue, rather than the qualitative changes, influence the mechanical competence of the bone. PMID- 8354679 TI - Load-bearing capacity of corticocancellous bone grafts in the spine. AB - We investigated the relationship between the densities and areas of commonly used autogenous tricortical bone grafts from the iliac crest and the fibula and their mechanical load-bearing abilities. Intact corticocancellous grafts, seven millimeters thick, were obtained during elective spinal arthrodeses from fifty six patients: from the anterior part of the pelvis in twenty-four patients, the posterior part of the pelvis in twenty-nine patients, and the fibula in three patients. The apparent densities and cross-sectional areas of the cortical and cancellous bone were measured with use of a specific computed-tomographic technique before the specimens were mechanically tested to failure in uniaxial compression. Specimens from the anterior superior iliac spine were able to bear significantly higher axial loads (average, 3230 newtons; range, 430 to 8112 newtons) than were those from the posterior superior iliac spine (average, 1458 newtons; range, 350 to 4639 newtons) (p < 0.001). The cancellous density was the most significant single factor in the prediction of the load to failure of the grafts from the iliac crest (adjusted r2 = 0.58; p < 0.0001). When all of the physical variables (the cancellous and cortical densities and areas) were entered into a multiple-regression model, the combination of the cortical and cancellous densities and the cortical area was a good predictor (adjusted r2 = 0.68; p < 0.001) of the load to failure. The fibular grafts were stronger than those from the other two sites, but they had the least over-all cross-sectional area and cancellous bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354680 TI - Genetic transmission of fibrodysplasia ossificans progressiva. Report of a family. AB - Fibrodysplasia ossificans progressiva is a rare connective-tissue disorder characterized by congenital malformation of the great toes and by progressive heterotopic ossification of the tendons, ligaments, fasciae, and skeletal muscles. We document the genetic transmission of fibrodysplasia ossificans progressiva from a sporadically affected father to each of his three children: two daughters and a son. Previous consideration of a genetic etiology was based on the fact that the disease has been reported in several sets of monozygotic twins, that an increased paternal age has been associated with sporadic occurrences of the disorder, and that there have been several reports of genetic transmission in the remote past. Although an autosomal-dominant genetic transmission has long been suspected, the findings in the family reported on here provide confirmation for such inheritance and a basis for the diagnosis and counseling of patients who have this disease. PMID- 8354681 TI - Deep peroneal-nerve injury as a result of arthroscopic meniscectomy. A case report and review of the literature. PMID- 8354682 TI - Aneurysmal bone cyst arising after tibial fracture. A case report. PMID- 8354683 TI - Persistent synchondrosis of the second cervical vertebra simulating a hangman's fracture in a child. Report of a case. PMID- 8354684 TI - Blindness as a complication of intraoperative positioning. A case report. PMID- 8354685 TI - Arthroscopy of the ankle and foot. PMID- 8354686 TI - Magnetic resonance-imaging studies of the shoulder. Diagnosis of lesions of the rotator cuff. PMID- 8354687 TI - Isokinetic and isometric measurement of strength of external rotation and abduction of the shoulder. PMID- 8354688 TI - Arthroplasty of the metatarsophalangeal joint with a double-stem silicone implant. PMID- 8354689 TI - Fixation with a single screw for slipped capital femoral epiphysis. PMID- 8354690 TI - MAS6 encodes an essential inner membrane component of the yeast mitochondrial protein import pathway. AB - To identify new components that mediate mitochondrial protein import, we analyzed mas6, an import mutant in the yeast Saccharomyces cerevisiae. mas6 mutants are temperature sensitive for viability, and accumulate mitochondrial precursor proteins at the restrictive temperature. We show that mas6 does not correspond to any of the presently identified import mutants, and we find that mitochondria isolated from mas6 mutants are defective at an early stage of the mitochondrial protein import pathway. MAS6 encodes a 23-kD protein that contains several potential membrane spanning domains, and yeast strains disrupted for MAS6 are inviable at all temperatures and on all carbon sources. The Mas6 protein is located in the mitochondrial inner membrane and cannot be extracted from the membrane by alkali treatment. Antibodies to the Mas6 protein inhibit import into isolated mitochondria, but only when the outer membrane has been disrupted by osmotic shock. Mas6p therefore represents an essential import component located in the mitochondrial inner membrane. PMID- 8354691 TI - Localization of Drosophila retinal degeneration B, a membrane-associated phosphatidylinositol transfer protein. AB - The Drosophila retinal degeneration B (rdgB) mutation causes abnormal photoreceptor response and light-enhanced retinal degeneration. Immunoblots using polyclonal anti-rdgB serum showed that rdgB is a 160-kD membrane protein. The antiserum localized the rdgB protein in photoreceptors, antennae, and regions of the Drosophila brain, indicating that the rdgB protein functions in many sensory and neuronal cells. In photoreceptors, the protein localized adjacent to the rhabdomeres, in the vicinity of the subrhabdomeric cisternae. The rdgB protein's amino-terminal 281 residues are > 40% identical to the rat brain phosphatidylinositol transfer protein (PI-TP). A truncated rdgB protein, which contains only this amino-terminal domain, possesses a phosphatidylinositol transfer activity in vitro. The remaining 773 carboxyl terminal amino acids have additional functional domains. Nitrocellulose overlay experiments reveal that an acidic amino acid domain, adjacent to the PI transfer domain, binds 45Ca+2. Six hydrophobic segments are found in the middle of the putative translation product and likely function as membrane spanning domains. These results suggest that the rdgB protein, unlike the small soluble PI-TPs, is a membrane-associated PI-TP, which may be directly regulated by light-induced changes in intracellular calcium. PMID- 8354692 TI - Molecular characterization of mammalian cylicin, a basic protein of the sperm head cytoskeleton. AB - The cytoskeletal calyx structure surrounding part of the nucleus of the mammalian sperm head contains two major kinds of basic proteins, i.e., the approximately 60 kD calicin and a group of very basic (IEP > pH 10) polypeptides ranging in size from approximately 58 to approximately 100 kD ("multiple band proteins," MBPs). We have produced MBP-specific mAbs and have isolated a bovine and a human cDNA clone encoding one of these proteins, termed "cylicin" (from the Greek word c eta kv lambda l zeta for cup or beaker). Bovine cylicin I of a calculated molecular weight of 74,788 contains a high proportion (29%) of positively charged amino acids, resulting in an IEP of 10.55, numerous KKD tripeptides, and is characterized by an organization of the central part of the molecule in nine repeating units of maximally 41 amino acids each of which according to prediction analysis should tend to form an alpha helix. The identity of the polypeptide has been proven by direct amino acid sequencing of > 14 different fragments and by experiments using antibodies raised against a partial cDNA-derived protein segment produced in E. coli. By Northern blot analysis we have identified the 2.4 kb cylicin I mRNA only in testis. The unusual cytoskeletal protein cylicin is compared with other proteins and its possible architectural role during spermiogenesis is discussed. PMID- 8354693 TI - Neurotrophins and their receptors in rat peripheral trigeminal system during maxillary nerve growth. AB - We examined the expression of the neurotrophins (NTFs) and their receptor mRNAs in the rat trigeminal ganglion and the first branchial arch before and at the time of maxillary nerve growth. The maxillary nerve appears first at embryonic day (E)10 and reaches the epithelium of the first branchial arch at E12, as revealed by anti-L1 immunohistochemistry. In situ hybridization demonstrates, that at E10-E11, neurotrophin-3 (NT-3) mRNA is expressed mainly in the mesenchyme, but neurotrophin-4 (NT-4) mRNA in the epithelium of the first branchial arch. NGF and brain-derived neurotrophic factor (BDNF) mRNAs start to be expressed in the distal part of the first brachial arch shortly before its innervation by the maxillary nerve. Trigeminal ganglia strongly express the mRNA of trkA at E10 and thereafter. The expression of mRNAs for low-affinity neurotrophin receptor (LANR), trkB, and trkC in trigeminal ganglia is weak at E10, but increases by E11-E12. NT-3, NT-4, and more prominently BDNF, induce neurite outgrowth from explant cultures of the E10 trigeminal ganglia but no neurites are induced by NGF, despite the expression of trkA. By E12, the neuritogenic potency of NGF also appears. The expression of NT-3 and NT-4 and their receptors in the trigeminal system prior to target field innervation suggests that these NTFs have also other functions than being the target-derived trophic factors. PMID- 8354694 TI - Activated mouse astrocytes and T cells express similar CD44 variants. Role of CD44 in astrocyte/T cell binding. AB - The CD44 adhesion molecule is expressed by astrocytes, glial-type cells which exhibit features of accessory cells for immune responses in the central nervous system. In primary cultures of mouse astrocytes, we have observed that surface expression and mRNA levels of CD44 are induced following stimulation with either PMA, or tumor necrosis factor alpha plus gamma interferon. Comparison of CD44 splice variants expressed by astrocytes and a T cell hybridoma shows that upon activation, both cell types express a similar pattern of CD44 transcripts. Thus, in both cell types, CD44 transcripts are produced which contain additional exons, including the exon v6 (known to be expressed by in vivo activated lymphocytes and by metastatic variants of tumor cells) as well as variants of larger size. In the autoimmune disease multiple sclerosis, activated T cells cross the blood-brain barrier and lead to inflammation in the central nervous system. Analysis of mice with experimental allergic encephalomyelitis, frequently used as an animal model of multiple sclerosis, shows that CD44 is induced in vivo on glial cells surrounding inflammatory lesions. Using an in vitro model for adhesion between T cells and astrocytes, we have found a correlation between the activation state of these cells and their adhesion potential. Dose-dependent inhibition of adhesion by hyaluronate and by anti-CD44 monoclonal antibody KM81 shows that CD44 is involved in the adhesive interactions between T cells and astrocytes. PMID- 8354695 TI - Murine clusterin: molecular cloning and mRNA localization of a gene associated with epithelial differentiation processes during embryogenesis. AB - Clusterin is a broadly distributed glycoprotein constitutively expressed by various tissues and cell types, that has been shown to be involved in cell-cell adhesion and expressed during cellular differentiation in vitro. To assess the suggested participation of clusterin in these processes in vivo, we have cloned the cDNA encoding murine clusterin and studied the cellular distribution of clusterin mRNA during murine embryogenesis. Sequence analysis of the cDNA encoding murine clusterin revealed 92 and 75% sequence identity with the rat and human cDNAs, respectively, and conservation of the predicted structural features which include alpha-helical regions and heparin-binding domains. From 12.5 d of development onwards, the clusterin gene is widely expressed in developing epithelia, and selectively localized within the differentiating cell layers of tissues such as the developing skin, tooth, and duodenum where proliferating and differentiating compartments are readily distinguished. In addition, transient and localized clusterin gene expression was detected in certain morphogenetically active epithelia. In the lung, abundant gene transcripts were detected in cuboidal epithelial cells of the terminal lung buds during branching morphogenesis, and in the kidney, clusterin gene expression in the epithelial cells of comma and S-shaped bodies coincided with the process of polarization. Our results demonstrate the in vivo expression of the clusterin gene by differentiating epithelial cells during murine embryogenesis, and provide novel evidence suggesting that clusterin may be involved in the differentiation and morphogenesis of certain epithelia. PMID- 8354697 TI - The nuclear pore complex. PMID- 8354696 TI - Integrin-mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels. AB - Electrical signals elicited by integrin interaction with ECM components and their role in neurite outgrowth were studied in two clones (N1 and N7) isolated from 41A3 murine neuroblastoma cell line. Although the two clones similarly adhered to fibronectin (FN) and vitronectin (VN), this adhesion induced neurite outgrowth in N1 but not in N7 cells. Patch clamp recordings in whole cell configuration showed that, upon adhesion to FN or VN but not to platelet factor 4 (PF4), N1 cells undergo a marked (approximately equal to 20 mV) hyperpolarization of the resting potential (Vrest) that occurred within the first 20 min after cell contact with ECM, and persisted for approximately 1 h before reverting to the time zero values. This hyperpolarization was totally absent in N7 cells. A detailed analysis of the molecular mechanisms involved in N1 and N7 cell adhesion to ECM substrata was performed by using antibodies raised against the FN receptor and synthetic peptides variously competing with the FN or VN binding to integrin receptor (GRGDSP and GRGESP). Antibodies, as well as GRGDSP, abolished adhesion of N1 and N7 clones to FN and VN, revealing a similar implication of integrins in the adhesion of these clones to the ECM proteins. However, these anti-adhesive treatments, while ineffective on Vrest of N7 cells, abolished in N1 cells the FN- or VN-induced hyperpolarization and neurite outgrowth, that appeared therefore strictly associated and integrin-mediated phenomena. The nature of this association was deepened through a comparative analysis of the integrin profiles and the ion channels of N1 and N7 cells. The integrin immunoprecipitation profile resulted very similarly in the two clones, with only minor differences concerning the alpha V containing complexes. Both clones possessed Ca2+ and K+ delayed rectifier (KDR) channels, while only N1 cells were endowed with inward rectifier K+ (KIR) channels. The latter governed the Vrest, and, unlike KDR channels, were blocked by Ba2+ and Cs+. By moving patched cells in contact with FN-coated beads, it was shown that KIR channel activation was responsible for the FN-mediated hyperpolarization of Vrest. Treatment with Pertuxis toxin (PTX) abolished this hyperpolarization and neurite outgrowth, indicating that a G protein is interposed between integrins and KIR channels and that the activation of these channels is required for neuritogenesis. In fact, the block of KIR channels by Cs+ abolished both hyperpolarization and neurite outgrowth, provided that the cation was supplied during the first two hours after N1 cell contact with FN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8354698 TI - Reversible effects of nuclear membrane permeabilization on DNA replication: evidence for a positive licensing factor. AB - We have investigated the mechanism which prevents reinitiation of DNA replication within a single cell cycle by exploiting the observation that intact G2 HeLa nuclei do not replicate in Xenopus egg extract, unless their nuclear membranes are first permeabilized (Leno et al., 1992). We have asked if nuclear membrane permeabilization allows escape of a negative inhibitor from the replicated nucleus or entry of a positive activator as proposed in the licensing factor hypothesis of Blow and Laskey (1988). We have distinguished these possibilities by repairing permeabilized nuclear membranes after allowing soluble factors to escape. Membrane repair of G2 nuclei reverses the effects of permeabilization arguing that escape of diffusible inhibitors is not sufficient to allow replication, but that entry of diffusible activators is required. Membrane repair has no significant effect on G1 nuclei. Pre-incubation of permeable G2 nuclei in the soluble fraction of egg extract before membrane repair allows semiconservative DNA replication of these nuclei when incubated in complete extract. Addition of the same fraction after membrane repair has no effect. Our results provide direct evidence for a positively acting "licensing" activity which is excluded form the interphase nucleus by the nuclear membrane. Nuclear membrane permeabilization and repair can be used as an assay for licensing activity which could lead to its purification and subsequent analysis of its action within the nucleus. PMID- 8354700 TI - Learning, forgetting, and retrieval of everyday material across the adult life span. AB - Levels and rates of acquisition and amounts of forgetting of name-face associations and grocery list items were assessed in a sample of 1,921 normal participants that was divided into five age groups (i.e., 17-39, 40-49, 50-59, 60 69, and 70+). Retrieval was assessed via the consistent long-term retrieval score (CLTR) from the Grocery List Selective Reminding Test (GLSRT). Substantial linear age-associated declines in level of acquisition were noted for both name-face associations and grocery list items. There was a significant age-related drop in rate of acquisition of name-face associations. Remarkably, very little forgetting occurred over a 40-min delay at any age on either measure. There was a significant linear age-related decline in retrieval efficiency for grocery list items, when variance due to both level of acquisition and retention was removed. The nature of age-associated memory decline and its possible neuroanatomic correlates is discussed. PMID- 8354699 TI - Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor. AB - Xenopus egg extracts treated with the protein kinase inhibitor 6 dimethylaminopurine (6-DMAP) are unable to support the initiation of DNA replication. Nuclei assembled in 6-DMAP extracts behave as though they are in G2, and will not undergo another round of DNA replication until passage through mitosis. 6-DMAP extracts are functionally devoid of a replication factor that modifies chromatin in early G1 before nuclear envelope assembly, but which is itself incapable of crossing the nuclear envelope. This chromatin modification is capable of supporting only a single round of semiconservative replication. The behavior of this replication factor is sufficient to explain why eukaryotic DNA is replicated once and only once in each cell cycle, and conforms to the previous model of a Replication Licensing Factor. Cell cycle analysis shows that this putative Licensing Factor is inactive during metaphase, but becomes rapidly activated on exit from metaphase when it can modify chromatin before nuclear envelope assembly is complete. PMID- 8354701 TI - Differential aspects of conceptual processing in the Category Test and Wisconsin Card Sorting Test. AB - Ninety-six veterans from neuropsychiatric wards were administered the Category Test (CT), Wisconsin Card Sorting Test (WCST), and a series of concept formation tests assessing attribute identification and rule learning. The CT and WCST shared only 30% common variance, and related to different facets of concept formation. The WCST was associated with attribute identification, which entails discrimination of relevant features, while the CT was more related to rule learning, which assesses the deduction of classification rules. The CT and WCST should not be regarded as similar measures of one construct such as "abstraction." Use of discrete scores from each test can help assess different aspects of concept formation. PMID- 8354702 TI - Adapting the Rivermead Behavioural Memory Test for use with children aged 5 to 10 years. AB - We describe modifications made to the Rivermead Behavioural Memory Test (RBMT) to make it appropriate for use with children. Results of a sample of 335 children aged 5 to 10 years, attending mainstream schools, are reported. Each child was given two of the four versions of the modified test for children together with a number of tests of memory and achievement from the Wechsler Intelligence Test for Children (Revised WISC-R), and the British Ability Scales (BAS). The children's version of the behavioural memory test (RBMTC) has good interrater and parallel from reliability. The validity of the RBMTC was established in two ways. First, with other tests of memory from the WISC and BAS. Second, a small (n = 36) group of children with severe epilepsy and memory difficulties, attending a residential school, were tested. The houseparents of these children were asked to complete rating scales on everyday memory performance. There was significant agreement between houseparents' observations and scores on the RBMTC (Spearman rank correlation = .71, p < .001), indicating that the test is indeed assessing everyday memory. PMID- 8354703 TI - Assessment of hand preference in two language-trained chimpanzees (Pan troglodytes): a multimethod analysis. AB - The nonhuman primate literature concludes that monkeys and apes do not exhibit handedness preferences at the population level. This discrepancy between human and nonhuman primate findings may be due to differences in the methods of assessment of handedness, lack of reliability between various measures of handedness, and a paucity of studies involving great apes. This paper presents the results of extensive hand preference studies with two language-trained chimpanzees (Pan troglodytes). Both naturalistic and experimental paradigms are described. In particular, various methodologic factors involved in handedness assessment, including the use of a hand preference measure previously used with human subjects were examined. Both chimpanzees exhibited a right-hand preference for fine motor tasks requiring manual dexterity. PMID- 8354704 TI - Course of insight disorder and emotional dysfunction following closed head injury: a controlled cross-sectional follow-up study. AB - Closed-head injury (CHI) patients at either 6 months (n = 24), 1 year (n = 19), or 2 to 3 years (n = 23) postinjury, were compared with a group of orthopedic control (OC) patients (n = 27). CHI patients assessed at 6 months postinjury experienced a Post-Traumatic Insight Disorder, in which they underreported the severity of their behavioural impairments. CHI patients in the 1 year and 2 to 3 year follow-up groups evidenced both greater insight about their level of behavioural impairment, and higher levels of emotional dysfunction. These findings suggested that the return of insight is associated with increased risk for emotional dysfunction. Implications of these findings for assessment and treatment of closed-head injury patients are discussed. PMID- 8354705 TI - Lexical decision performances in P-type dyslexic, L-type dyslexic, and normal reading boys. AB - Lexical decision performances in P-type dyslexic, L-type dyslexic, and normal reading boys were investigated using three-letter and four-letter words (familiar words) and nonwords presented in the central visual field. For words, P-type dyslexics displayed significantly longer latencies for four-letter than for three letter word decisions, whereas L-type dyslexics and normal readers did not. For nonwords, all subject groups showed significantly larger mean latencies for four letter than for three-letter nonword decisions. In general, the error data corresponded to the latency data. L-type dyslexics, however, made more errors during four-letter words than during three-letter words, although they had similar latencies in both conditions. The results are discussed with reference to the hypothesis that P-type dyslexics would use a sequential processing mode for reading familiar words, whereas L-type dyslexics would employ a parallel processing mode for reading familiar words. PMID- 8354706 TI - Proactive interference in patients with amnesia resulting from anterior communicating artery aneurysm. AB - Diencephalic and temporal amnesics display an excessive sensitivity to proactive interference (PI) in memory tasks of the AB/AC kind. There exists considerable controversy about the nature of this sensitivity to PI. Moreover, it is an open question whether such sensitivity to PI is an obligatory feature of amnesia, or rather an incidental result of frontal damage often reported in amnesics. This question was reexamined by enrolling patients with an operated aneurysm of the anterior communicating artery (ACoA) and matched controls for an AB/AC learning task of two lists of 12 paired-associate words. It appeared that ACoA patients, like diencephalic and temporal amnesics, did indeed display a marked sensitivity to PI when compared to normals (Exp. I), even when performance of both groups in the learning of the first list was equated (Exp. II). The distribution of errors made in learning the second list, as well as the correlations between performance in learning the second list and a Stroop test, suggest that sensitivity to PI in ACoA amnesics could be the consequence of an inability to suppress irrelevant information at retrieval due to defective inhibitory attentional mechanisms. Complementary data collected in a small sample of Korsakoff's amnesic subjects are also described. PMID- 8354707 TI - Digit Memory Test: unequivocal cerebral dysfunction and suspected malingering. AB - The Digit Memory Test (DMT) (Hiscock & Hiscock, 1989), a forced-choice test for detecting malingering, was administered to 27 patients with unequivocal cerebral dysfunction, 5 patients with postconcussional syndrome, 6 suspected malingerers and 10 normal controls. Results indicate that, even in patients with severe, but static cerebral dysfunction and unequivocal memory disorder, DMT performance is between 95% to 100% correct. By contrast, the 6 patients in whom malingering was seriously considered performed at a level much below the other three groups (74% correct) but not significantly below chance. The DMT may be helpful in evaluating patients suspected of malingering even when they do not score significantly below chance. PMID- 8354708 TI - Generative naming in Parkinson disease patients. AB - The generative naming ability (verbal fluency) of 88 idiopathic Parkinson disease (PD) patients was evaluated and compared to that of 21 Alzheimer disease (AD) patients and 43 normal age- and education-matched normal control subjects. The PD patients were classified according to whether they scored within the normal range on the Mini-Mental State Examination (MMSE), a score of 27 or higher, or in the abnormal range, a score of 26 or lower. Semantic and letter generative naming tasks were administered to assess verbal fluency. Results of the study provide evidence that letter category naming is inherently more difficult than semantic category naming; that age significantly affects generative naming; that PD patients with normal MMSE scores were significantly inferior to normal control subjects in generative naming even after the effects of age and mental status are controlled; that PD patients with non-normal MMSE scores performed like AD patients after controlling for the effects of age and mental status; and, that ideational perseveration is the most common type of error response for all subject groups. PMID- 8354709 TI - Models of cognitive deficit and statistical hypotheses: multiple sclerosis, an example. AB - The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures. PMID- 8354710 TI - Malingering and other validity considerations in the neuropsychological evaluation of mild head injury. AB - Eight malingerers (MPs) were identified via significantly below-chance symptom validity testing (SVT) within a sample of 106 consecutive admissions for neuropsychological evaluation. The resulting incidence of 7.5% is seen as a minimal estimate of malingering within the sample. Eight individuals who "passed" SVT but produced neuropsychological data of questionable validity were also identified (QVs). MPs and QVs were compared with matched controls on 14 measures that have been previously suggested as indicators of invalid neuropsychological data. MPs and QVs differed from controls on General Neuropsychological Deficit Scale, Fingertip Number Writing, and Digit Span. CVLT Recognition, Finger Agnosia, and Speech Perception differed for one of the target groups versus controls and had trends toward significance in the other group. However, many of the previously suggested invalidity signs were rare or absent. Reliance on these measures could result in overconfidence in the validity of neuropsychological data. PMID- 8354711 TI - A meta-analysis of the relative sensitivity of neuropsychological screening tests. AB - The National Institute of Mental Health recently formed a committee of experts which published a proposal for a lengthy neuropsychological test battery judged most apt to detect diffuse brain damage while covering a wide range of cognitive abilities. The purposes of the present study were (1) to assemble empirical evidence of the existence of statistically significantly sensitive screening tests across an equivalently wide range of functional domains, and (2) to present this evidence systematically, in such a manner as to help clinicians select subsets of screening tests manifesting greatest sensitivity to diffuse brain damage. It was found that in certain functional domains (speed of processing, problem solving, executive functions), marked differences in sensitivity occurred. Brief tests just as sensitive as time-consuming tests were also identified. The reader is cautioned about possible extraneous sources of the differences obtained (test and group selection bias, test reliability, test difficulty, procedural effects, Type I error). Nevertheless, it was concluded that a brief highly sensitive and functionally wide-ranging neuropsychological test battery for screening cases of putative diffuse brain dysfunction can be assembled. PMID- 8354712 TI - Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects. AB - This study retrospectively investigated the effect of left (LHS) versus right (RHS) hippocampal sclerosis on verbal memory, measured by means of the Paired Associate Learning and Logical Memory subtests of the Wechsler Memory Scale (WMS) administered as part of a routine preoperative assessment. Patients were selected for the presence of unilateral hippocampal sclerosis by means of preoperative magnetic resonance imaging (MRI) and postoperative neuropathology. The LHS patients (n = 20) were significantly worse on paired associate learning than RHS patients (n = 18), the performance of RHS patients being consistent with normative standards. In contrast, no laterality effect was seen on the immediate and delayed recall of passages; the evidence suggests that both groups performed at a mildly impaired level. It was suggested that the laterality of verbal memory is conditional upon specific task demands in patients with damage to mesial temporal structures. PMID- 8354713 TI - Implications of statistical tests of variance and means. AB - The primary purpose of this paper is to illustrate that tests for the homogeneity of variance in the statistical analysis of clinical neuropsychological data may provide unique information. Specifically, tests of variance homogeneity are more sensitive to outliers than the more commonly used tests of group means. Moreover, when both a test of means and of variance are done and the results compared, the nature of the deficit within the sample can be interpreted with greater confidence. PMID- 8354714 TI - Brain injury: a personal view. PMID- 8354715 TI - Reverse passive hemagglutination tests for rapid diagnosis of snake envenomation. AB - Reverse passive hemagglutination (RPHA) tests for the detection of six major poisonous snake venoms of Thailand were studied. Three different species of red blood cells i.e., sheep (SRBC), human (HRBC) and chicken (CRBC) were sensitized with protein A-affinity purified rabbit antivenom IgG using chromic chloride as a coupling reagent. The properties of these sensitized erythrocytes with regard to sensitivity, specificity, stability to venom enzymes and storage etc., were studied and compared. The sensitivities of the RPHA tests in venom detection were 2 to 635 ng/ml. Cross-reactions were observed with heterologous venoms at concentrations at least 62 times higher than those observed with homologous venoms. After treatment with glutaraldehyde, the coupled red blood cells showed reduced sensitivity but were stable at 4 degrees C from 1 to 12 months depending upon the antibody and the species of erythrocytes. The entire test required 60 to 120 min. The RPHA using fresh SRBC correctly identified various venoms in 48 of 59 (81.3%) serum samples and 16 of 26 (61.5%) wound swabs. Venom mis identifications were made in 2 sera (3.4%). In a comparison of 24 paired serum and wound swab samples, more positive identifications were made with serum than with swab samples but the difference was not statistically significant (p > 0.05). PMID- 8354716 TI - A simple, sensitive, dual mAb based ELISA for murine gamma interferon determination: comparison with two common bioassays. AB - Three assays of murine IFN gamma are compared in terms of sensitivity, intra- and inter-assay variability, specificity and simplicity. The widely used viral inhibition assay requires 48 hours, necessitates continuous maintenance and optimization of fibroblast growth, and exhibits the lowest sensitivity. Inhibition of WEHI-279 B cell [3H]thymidine incorporation requires 48-60 hours to quantitate IFN gamma production, can be subject to non-specific inhibition, and is also labor intensive. In both bioassays, specificity must be determined by the analysis of duplicate samples in the presence of neutralizing, IFN gamma-specific mAb. In contrast, a 24 hour, dual mAb ELISA, in which IFN gamma is captured by immobilized, purified rat IgG1 XMG 1.2 mAb and identified with biotinylated mAb R4-6A2 and streptavidin-alkaline phosphatase detects IFN gamma production > 0.05 U/ml. The quantitative range in this assay is typically from 1-100 U/ml. In addition to providing the greatest specificity and shortest duration, this ELISA exhibits the lowest coefficient of variation of the three assays compared. Collectively, assay characteristics such as sensitivity, absence of interference by other proteins, reproducibility, speed and simplicity support the conclusion that this dual mAb based sandwich ELISA represents a substantial improvement over inhibition of viral cytopathic effect or inhibition of WEHI-279 bioassays for characterization of antigen- or mitogen-driven IFN gamma production. PMID- 8354717 TI - Quantitative analysis of immunoglobulin G subclasses in the rat. AB - Quantitative ELISAs have been developed for the four immunoglobulin G (IgG) subclasses (IgG1, IgG2a, IgG2b and IgG2c) of the rat. These assays were shown to have excellent sensitivity, reproducibility and adequate specificity for studies of natural IgG and antigen-elicited IgG responses. The sensitivity (working range for each isotype assay) was: IgG1, 1.6 to 200 ng/ml; IgG2a, 8 to 200 ng/ml; IgG2b, 1.6 to 200 ng/ml; and IgG2c, 1.6 to 1000 ng/ml. The isotype sum and the direct assay of total plasma IgG agreed closely. The utility of these assays was demonstrated in a study of the development of total IgG and of the specific IgG response following immunization with tetanus toxoid (TT). For total IgG, the predominant isotype was IgG2b (64% of total IgG) followed by IgG2a (29%), IgG1 (4%) and IgG2c (3%). In contrast, the anti-TT response was mainly of the IgG1 subclass (57% of total anti-TT). These quantitative assays should prove useful for investigating the response to experimental vaccines and the influence of cytokines on class switching in vivo. PMID- 8354718 TI - Radioimmunoassay for rat B-type natriuretic peptide (BNP-45). AB - Rat BNP-45 is the main circulating form of BNP in rat plasma. To understand the role of BNP in physiological and pathophysiological conditions, a specific radioimmunoassay (RIA) for the quantitative determination of the peptide in plasma and tissues is necessary. An assay using rBNP-45 as the standard in conjunction with antisera directed against this peptide has not been described in the literature, though some investigators have reported values ranging from 0.73 2.0 pmol/L using either BNP-26 or BNP-32 as the standard peptide. Unfortunately, these forms of BNP do not exist in rat plasma. In our studies, we have developed a specific RIA for rBNP-45 using rBNP-45 as the standard peptide and Tyro-rBNP-45 as the radioligand. We have used two specific antisera for assay purposes; one against rBNP-45, and the second to a peptide composed of the first 20 amino acids of rBNP-45 (rBNP[1-20]). The recovery of various amounts of rBNP-45 added to control plasma was 50-80% depending on the method of extraction and purification. The interassay and intraassay coefficients of variation were 12% and 6% respectively. Values obtained were similar for blood sampled by either cardiac puncture, decapitation, or aortic puncture. The method was used to measure rBNP 45 in the plasma of normal (WKY) and Spontaneously Hypertensive (SHR) rats. The values obtained were 5.46 +/- 0.43 and 19.6 +/- 2.36 pmol/L respectively. The rat atrial natriuretic peptide (ANP[99-126]) values in the same extracts were 23.2 +/ 0.45 and 51.6 +/- 3.16 pmol/L. PMID- 8354719 TI - Radioimmunoassay of ganirelix in plasma or serum. AB - A procedure for the radioimmunoassay (RIA) of ganirelix in plasma or serum at concentrations as low as 0.050 ng/ml is described. Antiserum was produced by coupling the N-terminus glycyl analog of ganirelix to BSA by a carbodiimide reaction and immunizing rabbits with this conjugate. The antiserum did not crossreact with LHRH or with various ganirelix peptide fragments. For RIA, 125I labeled ganirelix was used as the tracer and a double antibody procedure was used to separate the free and bound fractions. No purification of the analyte was required prior to RIA. Accuracy of the method was assessed by adding known quantities of ganirelix to ganirelix-free plasma and determining the ratio of measured to added analyte. Linear regression analysis for the concentration range 0.050-50.0 ng/ml yielded a regression equation of y = 0.97x + 0.18, r = 0.999, where x is the amount added and y is the amount measured. Additional validation was obtained from an in vivo study in which [3H]-ganirelix was administered to monkeys and plasma clearance profiles were determined by RIA and an HPLC radiochemical method. The results were in agreement within experimental error of the two methods. Linear regression analysis of the comparative data gave the equation y = 0.92x + 33.7, r = 0.980, where x is the amount measured by RIA and y is the amount measured by HPLC-radiochemical analysis. PMID- 8354720 TI - Aging and microcirculatory dynamics in human gingiva. AB - There have been no published reports characterizing gingival vascular function in humans of different ages. In this study, we compared gingival vascular dynamics in 60 healthy male humans ranging in age from 18-75 years (young, 18-25 years (Y); middle, 35-45 years (M); old, 65-75 years (O), 20 subjects/group). Both videomicroscopy of individual microvessels and laser doppler flowmetry were employed to assess marginal gingival circulation. Systemic cardiopulmonary parameters were monitored as controls. The number of gingival vessels visible in a microscopic field was higher and the number of microvessels exhibiting active flow was lower in M and O compared to Y. There were no differences among age groups in laser doppler flow values (tissue blood flow) or in red blood cell velocity in individual vessels. Although not statistically significant with age there was a trend towards decreasing blood flow velocity in both the laser doppler and videomicroscopic measurements. Blood pressure increased slightly with age. Peripheral oxygen saturation was lower in O compared to Y and M. No differences were seen in heart rate, respiratory rate or end-tidal carbon dioxide concentration. The changes in blood pressure and oxygen saturation were expected. The differences in numbers of visible vessels and the number of vessels with active blood flow may reflect the way the gingival microcirculation adapts with age to changing nutritional needs or to microbial and/or mechanical challenge. PMID- 8354721 TI - A comparative study of electric toothbrushes for the effectiveness of plaque removal in relation to toothbrushing duration. Timerstudy. AB - The purpose of the present study was to test the plaque-removing efficacy of 4 different toothbrushes in relation to duration of toothbrushing. The brushes studied were a manual toothbrush (M), a conventional electric toothbrush--the Blend-a-Dent (BL), the Interplak (IP) and the Braun Plak Control (BPC). For this study, 20 subjects were selected. The study was divided into 5 experiments which differed only in respect to the brushing time. The available time in experiment 1 through 5 was 7.5, 15, 30, 45, 90 s per quadrant respectively. Prior to each experiment, all subjects were asked to abstain from oral hygiene procedures for at least 24 h. The efficacy of toothbrushing in each experiment was studied while one investigator (MAL) brushed the teeth of the subjects. In each subject, all 4 brushes were tested. Each brush was assigned to a quadrant in a random order. No toothpaste was used throughout this study. The amount of dental plaque was evaluated before and after brushing by means of the Silness & Loe plaque index at 6 sites around each tooth investigated. The results show an increase in efficacy for all brushes varying from 7.5 s per quadrant to 90 s per quadrant (mean plaque reduction in terms of percentage 7.5 s-90 s: M = 40%-75%, BL = 45%-82%, BPC = 51% 94%, IP = 64%-92%). The IP removed significantly more plaque than the other 3 after 7.5 s of brushing. From 15 s through 90 s, the IP and BPC were equally effective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354722 TI - Oral hygiene, periodontal conditions and carious lesions in patients treated with dental bridges. A 15-year clinical and radiographic follow-up study. AB - A longitudinal study, extending over a period of 15 years, was carried out in a group of 102 patients who received 108 bridges made by the senior students at the Dental Faculty, University of Oslo, in 1967/68. The study included 343 abutment teeth, and the remaining teeth in the same jaw which received the restoration, 525 in all, served as control. The oral hygiene, gingival condition, pocket depth, caries on crowned teeth, location of crown margins and changes of alveolar bone level were recorded during the study. During the first 10 years, the patients received oral hygiene prophylaxis every 6 months. The mean age of the patients at the beginning of the study was 48 years. Of the original group of 102 patients, 88 attended the clinical examination after 5 years, 71 after 10 years, and 55 after 15 years. The amount of plaque did not differ between the crowned teeth and the control teeth during the observation period, while GI score 2 and 3 was more frequent in crowned teeth than in the control teeth during this period. This was mainly observed when the crown margins were located sub-gingivally. A slight increase in mean pocket depth was recorded in the crowned teeth while the mean pocket depth for the control teeth remained at the same level during the 15 years. Caries lesions were recorded in 3.3% of the abutment tooth surfaces at the 5th year, in 10.0% at the 10th year and in 12.0% at the 15th year examination. No statistical differences in bone loss could be detected between the control teeth and the crowned teeth. PMID- 8354723 TI - Evaluating the efficacy of a new flossing aid. AB - The purpose of this clinical trial was to compare the efficacy of a new flossing aid (Flosser) with finger flossing on preventing plaque and gingival inflammation. 35 adults who did not use dental floss routinely were assigned randomly to one of 2 treatment groups (Flosser or finger flossing) in a 2-period, single-blind crossover study. After prophylaxis, subjects were instructed to use the flossing aid or finger floss 1 x per day and to continue brushing for 30 days. Gingival inflammation (GI & BPI) and plaque (PI) were assessed prior to the prophylaxis and at 30 days. After a 30 day "washout" period, subjects were again reassessed for gingival inflammation and plaque, given a prophylaxis, assigned the opposite treatment (2nd treatment period) that they received the first treatment period, and assessed (GI, BPI & PI) after 30 days. Comparing the mean difference of the 30-day buccal interproximal scores between the treatment groups (flossing aid scores minus finger flossing scores) showed that the mean differences with 95% CI were: -0.013 +/- 0.067 [GI], -0.017 +/- 0.044 [BP] and 0.019 +/- 0.014 [PI]. No statistically significant differences from zero (0.05 alpha) were observed using the t-test. There was a high level of compliance (90%) with the prescribed regiment, and subjects preferred (56%) the flossing aid slightly over finger flossing. Even though there were no statistically or clinically significant differences in gingivitis and plaque scores between the 2 flossing groups, the positive inclination for the flossing aid makes it a desirable addition to the armamentarium of preventive dentistry. PMID- 8354724 TI - Failure of adjunctive minocycline-HCl to eliminate oral Actinobacillus actinomycetemcomitans. AB - Considerable problems have been reported in the eradication of Actinobacillus actinomycetemcomitans from periodontal sites. The present communication describes the 2-year results of a comprehensive combined mechanical/surgical and adjunctive minocycline (200 mg/day for 3 and another 2 weeks) treatment regimen in 28 patients with A. actinomycetemcomitans-associated periodontitis. Elimination of A. actinomycetemcomitans at periodontal sites was a prerequisite for gain of clinical attachment of > or = 2 mm or decrease of probing depth to < or = 4 mm after subgingival scaling plus minocycline (p < 0.01). Whereas 2 years after active treatment A. actinomycetemcomitans could not be detected at monitored sites in 23 patients, the organism was found on buccal mucosa and in saliva in 17 and 12 cases, respectively. One or 2 years after periodontal surgery, there was a significant association between log10-numbers of A. actinomycetemcomitans in buccal samples and numbers of residual pockets of > or = 7 mm as well as gingival sites with overt gingivitis (R2 = 0.687, p < 0.001). Present results indicate failure of an even prolonged administration of adjunctive minocycline to eliminate oral A. actinomycetemcomitans in most cases of A. actinomycetemcomitans associated periodontitis. PMID- 8354725 TI - Secnidazole concentrations in plasma and crevicular fluid after a single oral dose. AB - Metronidazole and related nitroimidazole derivatives, including ornidazole and tinidazole, have been used successfully in the treatment of periodontal diseases. The purpose of this study was to measure secnidazole (another nitroimidazole derivative) concentrations in plasma and gingival crevicular fluid (GCF) after intake of a single oral dose. Secnidazole concentrations were estimated in 11 human healthy volunteers after a single dose of 2 g taken orally. Samples of blood and GCF were collected before intake and during the following 72 h. A high performance liquid chromatography (HPLC) method has been developed for the determination of secnidazole in microsamples (1 to 3 microliters) of GCF. The mean peak blood and GCF levels were equal to 40.5 +/- 9.4 micrograms ml-1 at 2 h in blood and 26.4 +/- 7.0 micrograms ml-1 at 1 h in GCF, respectively. Apparent elimination half-life was 28.8 h (blood) and 30.4 h (GCF), respectively. These results show that the rate and extent-absorption of secnidazole are slightly higher in blood than in GCF, but the elimination of the drug is similar in the two body fluids. PMID- 8354726 TI - Pilot clinical study of a fluoride resin and conditioning paste for desensitising dentine. AB - The clinical trial was carried out on 34 'hypersensitive' teeth in 10 subjects. Dentine sensitivity was measured as the pain perception thresholds to controlled air and probe stimuli. In each subject, pairs of teeth of comparable initial sensitivity were randomly assigned to a test (T) or control (C) treatment. All teeth were cleaned and a conditioning paste applied. Group T was treated with a topically-applied light-cured resin; Group C received a placebo, sham light cured. Air sensitivity was remeasured after treatment, and the procedures were repeated after 1, 2, and 3 weeks. When comparing air thresholds before and after treatment at each visit, the test agent caused significantly greater reduction in sensitivity than the control. The median increase in air threshold in the test group was 2.5 s at visit no. 1, 1.3 s at visit no. 2 and 0.8 s at visit no. 3. Comparisons of the initial thresholds at each visit showed no significant long term changes in sensitivity in either group. PMID- 8354727 TI - IL-1 in gingival crevicular fluid following closed root planing and papillary flap debridement. AB - Interleukin (IL)-1 alpha and beta are cytokines which can mediate inflammatory, bone resorbing, and reparative effects in the periodontium, but few longitudinal data exist exploring their role following periodontal therapy. This study examined gingival crevicular fluid (GCF) concentrations of IL-1 alpha and IL-1 beta at sites with shallow sulci (SS) or inflamed moderate/advanced pockets (M/AP) before and 6 months after treatment with closed scaling/root planing (SC/RP) or papillary flap debridement (PFD), all in the same subject (n = 14 patients). No significant differences were noted in IL-1 alpha or beta concentrations (determined with two-site enzyme-linked immunosorbent assays) between SS and M/AP sites at baseline. While both therapies improved clinical parameters of periodontal disease, IL-1 alpha concentration increased significantly (p < 0.05) in M/AP-PFD sites 6 months after treatment, but were unchanged in other groups. IL-1 beta concentrations were numerically lower after therapy, except for a significant increase (p < 0.05) in M/AP-PFD sites. These data suggest that surgical wound healing in an inflamed, plaque-infected site (M/AP-PFD) results in prolonged production of IL-1, which may be a reflection of the extent of tissue trauma and delayed wound healing. In spite of increased IL-1 levels, these sites demonstrated significant short-term improvement in clinical attachment level (+ 1.8 mm, p < or = 0.001) postoperatively. PMID- 8354728 TI - Healing in periodontal defects treated by decalcified freeze-dried bone allografts in combination with ePTFE membranes. Assessment by computerized densitometric analysis. AB - This study quantitatively assessed radiographic changes in alveolar bone density by computer-assisted densitometric image analysis (CADIA) in periodontal defects that were treated with decalcified freeze dried bone allograft (DFDBA) alone or in combination with interproximal expanded polytetrafluroethylene membranes (ePTFE). The radiographic changes where then analyzed for correlation with the clinically assessed changes. The radiographic changes were evaluated on standardized radiographs of treated sites treated prior to, 1 week after surgery, and 6 months post-operatively. 15 patients with one pair of bilateral interproximal periodontal defects of similar morphology and > or = 6 mm in pocket depth participated. Analysis of the changes 6 months after treatment showed that the increases in density in the defect areas that received the graft were significantly greater than the adjacent areas (p < 0.001). These adjacent areas, in contrast, demonstrated significantly larger loss in radiographic density than the defect area (p < 0.001). The placement of DFDBA into the defects produced in itself significant increases in radiographic density, as illustrated by the results of one week which remained at six months. Utilization of ePTFE addition to DFDBA did not lead to additional radiographic gains in the defect area. While at one week the analysis suggested increased resorption by the combined treatment over grafting alone, such differences did not persist at 6 months post-surgery. Analysis comparing CADIA derived values for change with those of the clinical assessment revealed some associations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354729 TI - Healing in periodontal defects treated by decalcified freeze-dried bone allografts in combination with ePTFE membranes (I). Clinical and scanning electron microscope analysis. AB - This study clinically evaluates the use of decalcified freeze-dried bone allograft (DFDBA) in conjunction with an expanded polytetrafluoroethylene (ePTFE) membrane specifically designed for the treatment of interproximal intraosseous defects. It also examines by SEM, plaque contaminated membranes retrieved from patients. 15 advanced periodontitis patients with two bilateral interproximal probing depths of > or = 6 mm participated. After hygiene phase, measurements were made to determined soft tissue recession, pocket depth, clinical attachment levels and amount of keratinized tissue. Defects from each pair were randomly treated with ePTFE plus DFDBA (experimental) or DFDBA alone (control). Measurements were made during the surgery to determine crestal resorption, defect resolution and defect fill. Membranes were removed at 4 to 6 weeks and analyzed by SEM. Each site was surgically reentered and measurements repeated at six months. Both groups showed clinical and statistically significant changes when compared to baseline (P < 0.01), but no difference between groups. The experimental group showed increased soft tissue recession vs control group, 0.9 versus 0.4 mm, and loss of keratinized tissue 1.6 versus 0.1 mm (P < 0.0001). Control sites showed a 58% bone fill while experimental sites had 70% bone fill. There were no clear patterns of microbial colonization or cell adherences in either side of the membrane. It was concluded that the presence of plaque on the membranes did not compromise the initial clinical healing during the first 4-6 weeks. Results suggest a beneficial effect with the use of either technique for the treatment of intraosseous defects. PMID- 8354730 TI - Platelet-derived growth factor and dexamethasone combined with a collagen matrix induce regeneration of the periodontium in monkeys. AB - Platelet-derived growth factor (PDGF) and the glucocorticoid dexamethasone combined with a collagen carrier matrix (CM) induced regeneration of the periodontium in monkeys. Regeneration was stringently defined as: (1) new cementum, (2) new supra-crestal bone extending coronally from the residual alveolar interdental septum and (3) functionally-oriented periodontal ligament fibers attaching new cementum to new bone. A single application of PDGF/dexamethasone/CM or CM was placed in debrided lesions of experimental periodontitis displaying 3-5 mm of attachment loss associated with horizontal and angular bony defects. Regeneration, judged histologically by these criteria and quantified by computer assisted histomorphometry after 4 weeks, was present only in PDGF/dexamethasone/CM treated lesions and not in those treated with CM or debridement alone. PDGF/dexamethasone/CM induced 5-fold more new cementum and ligament, and 7-fold more supra-crestal bone than control treatments. The presence of substantial amounts of regenerated periodontium including increased height of the alveolar bone; fill of vertically resorbed interdental alveolar septa in PDGF/dexamethasone/CM treated lesions suggests that this combination may provide a new therapeutic agent for the regeneration of lesions of periodontitis associated with horizontal as well as angular bony defects. PMID- 8354731 TI - Autotransplantation of a tooth using guided tissue regeneration. AB - Autotransplantation is an alternative treatment to replace missing or periodontally-involved hopeless teeth. A prerequisite for performing this procedure is having a recipient site with sufficient bone volume to support the transplant. Often, however, crestal bone resorption following tooth extraction or periodontitis results in a reduced alveolar ridge with inadequate dimensions to properly house the transplant. In these cases, the procedure is contraindicated. A case is presented in which the biologic principle of guided tissue regeneration was used to gain periodontal support around an autotransplanted 3rd molar. The results suggest the potential use of guided tissue regeneration in conjunction with autotransplantation. This may represent a new area in reconstructive dentistry. PMID- 8354732 TI - Unrelated agranulocytosis in a patient taking clozapine. PMID- 8354733 TI - Effects of fluvoxamine, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers. AB - The effects of fluvoxamine (50 or 100 mg), alone and in combination with ethanol (0.8 g/kg), on psychomotor and cognitive performance and on autonomic nervous system reactivity were studied in healthy male volunteers. Fluvoxamine produced neither serious psychomotor or cognitive impairment nor alterations in autonomic nervous system functioning at these doses. There was no evidence that fluvoxamine exacerbated, or improved, ethanol-induced impairments of memory or any other measures evaluated. Fluvoxamine tended to improve recognition, but not free recall, of words. PMID- 8354734 TI - Interindividual variations of desmethylation and hydroxylation of clomipramine in an Oriental psychiatric population. AB - We measured the concentrations of clomipramine and its metabolites, N desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, and 8 hydroxyclomipramine in plasma in 92 Japanese psychiatric patients receiving clomipramine hydrochloride (Anafranil, Ciba-Geigy Japan Limited, Takarazuka, Japan) by high-performance liquid chromatography. Although there were large interindividual variations of total drug concentrations and concentrations of parent or intermediate metabolic compounds in plasma, significant positive correlations were observed between these drug concentrations and daily doses of clomipramine hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for both desmethylation and hydroxylation varied substantially with 30- to 90-fold interindividual variations. Frequency distribution histograms and probit analyses of these parameters identified only one possible poor hydroxylator but no poor desmethylator of clomipramine. These results suggest that there are large interindividual variations of capacities for hydroxylation and desmethylation of clomipramine in the Oriental population and that therapeutic drug monitoring is essential in clinical practice to reduce the adverse effects of clomipramine and to prevent poor response to clomipramine. PMID- 8354735 TI - Pretreatment systolic orthostatic blood pressure and treatment response in geriatric depression: a revisit. AB - Three previous studies have found significant positive correlations between pretreatment systolic orthostatic blood pressure (PSOP) and tricyclic antidepressant (TCA) response in geriatric depression (i.e., the greater the pretreatment orthostatic drop, the greater the treatment response). The purposes of this study were to revisit the question of whether PSOP predicts TCA response and also to examine whether large systolic orthostatic pressure (SOP) is a state or trait variable in late-life depression. We retrospectively examined PSOP data collected from 48 elderly patients with recurrent unipolar depression treated with nortriptyline (mean level in plasma, 85.3) in the open, acute-treatment phase of an ongoing double-blind, placebo-controlled study of maintenance therapies in late-life depression. PSOP was not significantly correlated with treatment response as measured by the Hamilton Rating Scale for Depression at weeks 7 to 9 (r = -0.12, not significant). Likewise, a 10-mm PSOP cutoff did not significantly differentiate patients by responder status. We did find that all five of our placebo-randomized, maintenance therapy patients with PSOPs greater than 10 mm had marked decreases in their SOPs in the nortriptyline-free, well state. Thus, our findings fail to replicate earlier reports of PSOP predicting TCA response in geriatric depression. However, our results do preliminary suggest that large SOP may be state dependent. We discuss plans to study prospectively whether large SOP is state dependent and whether SOP is a clinically useful predictor of recurrence in late-life depression. PMID- 8354736 TI - Clozapine response and adverse effects in nine brain-injured patients. AB - Clozapine was used to treat nine brain-injured patients with psychotic symptoms or outbursts of rage and aggression refractory to other medications. Verbal and physical aggression decreased markedly in two patients, and one additional patient had a dramatic decrease in bizarre behaviors. Mild improvement occurred in three patients with a decrease in agitation and frequency of auditory hallucinations. Response was indeterminate in three patients because of inadequate length of treatment. The incidence of side effects appeared to be higher than expected, with seizures occurring in two of nine patients. These case reports illustrate that clozapine may be useful in the treatment of psychosis and aggressive behavior after brain injury, despite the occurrence of adverse effects. PMID- 8354737 TI - A predictive study of obsessive-compulsive disorder response to clomipramine. AB - Studies on predictive factors of the obsessive-compulsive disorder response to pharmacologic treatment, specifically clomipramine, are relatively scarce. Forty five patients treated for a mean period of 18.6 months were classified as having poor response, intermediate response and excellent response, defined by change scores on the Yale-Brown Obsessive-Compulsive Scale. Poor and intermediate response patients were grouped together and compared with the excellent response subgroup. Univariate analysis showed length of illness, family history (siblings), initial compulsiveness score, and cleaning rituals as significant predictors. Two multiple regression analyses with these as independent or predictive variables showed higher initial scores on the Yale-Brown Obsessive Compulsive Scale associated with poorer response to treatment but, most importantly, cleaning rituals as a predictor of poor or modest response to clomipramine. It may be important for the clinician to assess cleaning habits separately from the more frequently mentioned obsessive-compulsive symptom, hand washing. This distinction may have important clinical, therapeutic, and prognostic implications. PMID- 8354738 TI - Unrelated agranulocytosis in a patient taking clozapine. PMID- 8354739 TI - Sertraline-induced akathisia. PMID- 8354740 TI - Dystonic reaction associated with fluvoxamine. PMID- 8354741 TI - Assessment of treatment-resistant major depression--The Michigan Adequacy of Treatment Scale. PMID- 8354742 TI - Paradoxical mood shifts to euthymia or hypomania upon withdrawal of antidepressant agents. PMID- 8354743 TI - Two-year clinical evaluation of two dentine-adhesive systems in cervical lesions. AB - Two commercially available dentine-adhesive systems, Tenure and Tripton, were tested in two different cavity designs by placing 132 Class V composite restorations in cervical lesions of 35 patients. In Group A, the cervical restorations were placed totally in dentine without any intentional enamel involvement. In Group B, they were placed in dentine with adjacent enamel margins bevelled and acid etched. The retention rate, the evidence of clinical microleakage, and the marginal integrity were monitored over a 2-year period. The results of this clinical investigation indicate a high failure rate when only dentinal bonding was involved. A loss rate of 30% for Tenure and 55% for Tripton was noted in Group A after 2 years of clinical service. However, both adhesive systems used in combination with micromechanical retention on the enamel border (Group B) performed extremely well with only one restoration each having debonded over the 2-year period. Identically, marginal integrity and evidence of clinical microleakage more severely deteriorated with time for the Group A restorations in comparison with their Group B counterparts. In summary, the overall results were more positive for Tenure than for Tripton. It is concluded that micromechanical retention by acid etching of the enamel margin is still indispensable for the clinical success of cervical Class V composite restorations, primarily for retention and clinical microleakage and also, but to a lesser degree, for marginal adaptation. PMID- 8354744 TI - A 3-year follow-up study on single implant treatment. AB - The purpose of this study was to investigate restorative and postinsertion problems in patients provided with single implant supported restorations. Fifty consecutive single implant patients were reviewed over a period of 3 years following placement of artificial crowns. One (1.4%) of the 70 inserted implants was lost during the follow-up period, which gives a cumulative success rate of 98.5%. The most frequent complication was loosening of the single tooth abutment screw. This problem was associated with fistulas during the first year of clinical service. A more severe complication was that three adjacent teeth had to be endodontically treated due to accidental devitalization from surgical trauma during implant insertion. The mean marginal bone level adjacent to the implants was reduced 0.5 mm from crown insertion to the third annual review. PMID- 8354745 TI - A prospective study of the survival of chemically activated anterior resin composite restorations in general dental practice: 5-year results. AB - The principals of 26 general dental practices agreed to use six chemically activated resin composite restorative materials to restore Class III and Class V lesions and record information concerning their performance over a period of 5 years. The information collected was analysed by actuarial methods to assess the clinical longevity and reasons for replacement as perceived by the dentists operating in the General Dental Service in England. At the end of 5 years, 14 dentists provided sufficient returns for their data to be considered suitable for analysis. The database consisted of 2399 Class III and 1093 Class V restorations. The overall probability of survival at 5 years of Class III and Class V restorations was 62.9% and 71.8% respectively. The difference in performance between the six restorative materials was small, with the probability of survival varying from 70.4 +/- 2.9% to 56.3 +/- 2.9% for the Class III restorations and 78.6 +/- 3.7% to 67.7 +/- 4.2% for the Class V restorations. The main reasons for replacement were general surface discoloration, secondary caries and fracture. The chemically activated composite restorative materials available at the time of initiating this study produced comparable performances in general dental practice when used without enamel and dentine bonding techniques. This suggests that more general practice-based clinical studies are needed to determine whether or not improvements in materials and techniques are effectively transferred to the general practice situation. PMID- 8354746 TI - A simple method for monitoring mutans streptococci in margins of restorations. AB - Plaque material collected from margins of restorations using a sharp toothpick was streaked across one and the same plastic strip from a commercially available test kit and inoculated in a liquid medium containing bacitracin. The reproducibility of the method was good. The method is simple, inexpensive and suitable for the chairside demonstration of the colonization of mutans streptococci in localized areas of the mouth, such as margins of restorations. PMID- 8354747 TI - Inhibition of serum albumin flux across exposed dentine following conditioning with GLUMA primer, glutaraldehyde or potassium oxalates. AB - A variety of medicaments used on dentine in various treatment procedures may cause a reduction in dentine permeability. By observing the flow of endogenous serum albumin across exposed dentine, agents known to promote dentine bonding of restorative resins or retard dentine sensitivity were assessed regarding their capacity to arrest dentinal fluid flow. Experiments were conducted in young adult macaque monkeys employing Class V cavity preparations in incisors and canines. A diffusion-in-gel-enzyme-linked-immunosorbent-assay (DIG-ELISA) was used to quantitate serum albumin in effluents from these cavities at various time periods following either no treatment or topical application with GLUMA primer, glutaraldehyde or potassium oxalates. While in untreated cavities serum albumin continued to flow even after a period of 1 week, a substantial reduction or complete cessation of serum albumin flux was seen following topical application of the agents tested, suggesting a durable effect on dentinal fluid flow. No difference between agents was observed. Further cutting of the cavity bottom a few tenths of a millimetre resulted in renewed flow of serum albumin. Data suggest that the solutions tested are capable of reducing dentinal fluid flow onto exposed dentine surfaces. PMID- 8354748 TI - Air humidity: a detrimental factor in dentine adhesion. AB - Successful dentine adhesion may be negatively influenced by intrinsic and extrinsic dentine wetness. Testing the influence of high humidity levels during the application of bonding systems is therefore relevant. It was the aim of this study to investigate in vitro the sensitivity to air humidity of the dentine bond strength for some commercially available bonding systems. Four bonding systems were tested in vitro on human molars at temperature/humidity levels of 25 degrees C and 40% relative humidity (RH) as well as 35 degrees C and 95% RH. Four operators each made two samples of the respective treatment combinations. After shear bond testing a three-way ANOVA was carried out. Only the factors 'material', 'humidity' as well as their interaction were statistically significant. The factor 'operator' did not exert a significant influence on the shear bond strength. For the 'clinically dry' group statistically significant differences were found between all materials (P < 0.001). In the 'high humidity' setting too, significant differences were found between materials (P < 0.001). The shear bond strength values ('high humidity') were very low (< 3 MPa) for Gluma 2000, Denthesive and Syntac, while the mean values for Scotchbond Multi Purpose were significantly higher (12 MPa; P < 0.001). It was concluded that in general bonding systems are highly sensitive to extrinsic dentine wetness, resulting in very low adhesion values at high humidity. PMID- 8354749 TI - CO2 laser and the diagnosis of occlusal caries: in vitro study. AB - The diagnosis of small lesions in pit and fissure sites is becoming increasingly problematical. This study was designed to evaluate, in vitro, the potential use of a carbon dioxide (CO2) laser technique as an aid to the diagnosis of incipient pit and fissure caries. Vaporization of the organic material in the 'early' carious lesion should lead to its carbonization and thus make it more conspicuous. Pilot studies were carried out to identify lasing parameters which produced no visible effect on sound enamel but which caused charring (carbonization) of white spot fissure lesions. Fifty extracted human molars and premolars were air-polished on the occlusal surfaces and independently scored clinically for caries, both before and after lasing. The teeth were subsequently sectioned and examined histologically. Of the 37 sites histologically scored as sound or exhibiting precavitation lesions, eight were correctly scored as sound both prelasing and postlasing. Of the 29 precavitation lesions detected histologically, five were detected clinically prelasing and 11 were detected postlasing. This 21% difference in the sensitivity of caries diagnosis between the prelasing and postlasing examinations was statistically significant (at the 95% level). There were no false-positive caries diagnoses. Further research, in particular the refining of lasing parameters employed, is indicated. PMID- 8354750 TI - Flow injection analysis of formaldehyde leached from denture-base acrylic resins. AB - Formaldehyde is responsible for allergic inflammation in acrylic denture wearers and the quantitation of formaldehyde is necessary to study its leaching from denture-base materials. Flow injection analysis was developed to quantify the formaldehyde leached from acrylic resins. Different resins were immersed in aqueous solvents at 37 degrees C and the immersion solutions were directly injected into the flow system, in which formaldehyde was converted on-line to a fluorescent derivative and its fluorescence was detected. Under the optimized conditions, the leached formaldehyde could be quantified in a short time (within 4 min) with high sensitivity (pmol levels per injection) and high specificity (no fluorescent response to the other leachables). In leaching experiments, significant amounts of formaldehyde were leached from autopolymerized resins, but not from heat- and microwave-polymerized resins. PMID- 8354751 TI - Age changes in the viscoelasticity of a temporary soft lining material. AB - The viscoelastic properties of a widely used temporary soft lining material have been monitored in vivo and in vitro using a force distance probe. Over a period of 8 weeks' clinical use, Coe Soft demonstrated a significant and continued reduction in compliance with time, the reduction being particularly rapid over the first week. These changes were not associated with a reduction in measured lining thickness for which significant changes were not found. In vitro immersion in water, saline or artificial saliva was characterized by a rapid and significant reduction in compliance values over the first week. Further continued reductions in compliance values were only observed in artificial saliva over 8 weeks, and on prolonged immersion in distilled water over 96 weeks. All reductions in compliance were significantly less than those seen clinically. PMID- 8354752 TI - Optimal estimation of hearing-aid compression parameters. AB - A new procedure for measuring the attack and release time constants of a hearing aid compression circuit is presented in this paper. The procedure is based on a mathematical model of the response of a compression system to sudden increments or decrements in the amplitude of a sinusoidal excitation. The parameters of the model, which include the attack and release time constants, are fitted to the measured hearing-aid test-signal response using a minimum mean-squared error criterion. A computer simulation of a compression hearing aid is used to illustrate the behavior of the compression amplifier and to assess the accuracy of the estimated attack and release time constants. PMID- 8354753 TI - Localization using nonindividualized head-related transfer functions. AB - A recent development in human-computer interfaces is the virtual acoustic display, a device that synthesizes three-dimensional, spatial auditory information over headphones using digital filters constructed from head-related transfer functions (HRTFs). The utility of such a display depends on the accuracy with which listeners can localize virtual sound sources. A previous study [F. L. Wightman and D. J. Kistler, J. Acoust. Soc. Am. 85, 868-878 (1989)] observed accurate localization by listeners for free-field sources and for virtual sources generated from the subjects' own HRTFs. In practice, measurement of the HRTFs of each potential user of a spatial auditory display may not be feasible. Thus, a critical research question is whether listeners can obtain adequate localization cues from stimuli based on nonindividualized transforms. Here, inexperienced listeners judged the apparent direction (azimuth and elevation) of wideband noisebursts presented in the free-field or over headphones; headphone stimuli were synthesized using HRTFs from a representative subject of Wightman and Kistler. When confusions were resolved, localization of virtual sources was quite accurate and comparable to the free-field sources for 12 of the 16 subjects. Of the remaining subjects, 2 showed poor elevation accuracy in both stimulus conditions, and 2 showed degraded elevation accuracy with virtual sources. Many of the listeners also showed high rates of front-back and up-down confusions that increased significantly for virtual sources compared to the free-field stimuli. These data suggest that while the interaural cues to horizontal location are robust, the spectral cues considered important for resolving location along a particular cone-of-confusion are distorted by a synthesis process that uses nonindividualized HRTFs. PMID- 8354754 TI - The perception of temporal modulations by cochlear implant patients. AB - The perception of temporal modulations of pulsatile electric stimuli was measured in seven cochlear implant patients using the Cochlear Pty. Limited prosthesis. Four patients were postlingually deafened adults and three patients were young adults who were deafened very early in life. The first study measured detection thresholds for modulated pulse duration for a series of modulation frequencies and pulse rates. The shape of the detection thresholds as a function of modulation frequency, the temporal modulation transfer function, often resembled a low-pass filter with a 50-100-Hz cut-off frequency. Thresholds did not markedly vary across the different pulse rates for most patients. Thresholds were less than 10%-20% of the range of usable hearing for most patients. The second study compared detection thresholds for modulated pulse durations around different reference pulse durations: 50, 100, and 300 microseconds. Detection thresholds were generally proportional to the different reference pulse durations. The third study measured difference limens for the discrimination of modulation depth. The difference limens were similar to the detection thresholds for the same reference pulse duration and pulse rate. The three patients deafened very early in life showed more within-group variation in performance, and their overall levels of performance were poorer than those of the postlingually deafened adults. PMID- 8354756 TI - High rate otoacoustic emissions. AB - One of the practical problems of testing young children using evoked otoacoustic emissions (EOAEs) is that there is a need for the child to be quiet for a period of a minute or so. To achieve this can mean test periods of 10 min or longer. A new application of maximum length sequences (MLSs) to EOAEs is described that enables the test to be performed in a few seconds or less. Data from adults and neonates obtained at stimulation rates up to 840 clicks/s are presented and compared with conventionally derived emissions and the implications and applications of this new method are assessed. PMID- 8354755 TI - Acoustic impedance of the maternal abdomen. AB - Contact sensors to monitor fetal heart, breathing, and movement sounds with increased sensitivity and bandwidth are under development. To understand the inherent acoustical properties of the maternal abdomen and its interaction with these sensors, the driving-point impedance Z(j omega) was measured in nine women during their last trimester of pregnancy. An electromechanical shaker with a contact area of 2.85 cm2 produced abdominal vibrations between 10 and 500 Hz, and the resulting force and acceleration were measured. After digitally integrating the acceleration signal to obtain the velocity and removing the massive effects of the coupling between the shaker and the abdomen, Z(j omega) was estimated using spectral techniques. The imaginary part of Z(j omega) depicted a dominant compliance effect at low frequencies, a resonance at a frequency of 28 +/- 16 Hz (mean +/- s.d.), and a dominant mass effect at higher frequencies. The real part of Z(j omega) increased steadily with frequency. A series resistance-mass compliance (R-M-C) circuit modeled these characteristics of Z(j omega) well when R was allowed to exactly mimic the frequency dependence of the real part of Z(j omega). Estimated element values of 6.6 +/- 2.2 x 10(-3) kg for M, 2.1 +/- 1.4 x 10(-3) m/N for C, and roughly 10 Ns/m for R (at resonance) were similar to those estimated for other body tissues such as the thigh but quite different from that of the often-studied chest wall. PMID- 8354757 TI - A model of cochlear mechanics with outer hair cell motility. AB - The outer hair cell (OHC) is known to have the ability to change its length in response to voltage changes across its membrane. The apparent function of this OHC motility is to enhance the tuning of the basilar membrane. The model presented in this paper represents the displacement-to-voltage and voltage-to displacement transducers of the OHC explicitly, each as low-pass filter functions. The model results show that this OHC representation is sufficient to provide a model of cochlear mechanics with mechanical tuning at the inner hair cell which is comparable to the threshold tuning curves observed in single auditory nerve fibers. The enhancement of tuning provided by OHC motility can be interpreted as the combined action of a cochlear amplifier and a second filter. This model demonstrates that realistic cochlear tuning does not require intrinsic resonance in any cochlear structure other than the basilar membrane. PMID- 8354758 TI - Propagation of shock waves in elastic solids caused by cavitation microjet impact. I: Theoretical formulation. AB - To understand the physical process of the impingement of cavitation microjet and the resultant shock wave propagation in an elastic solid, a theoretical model using geometrical acoustics was developed. Shock waves induced in both the jet head (water) and the solid were analyzed during a tri-supersonic impact configuration when the contact edge between the jet head and the elastic boundary expands faster than the longitudinal wave speed in the solid. Impact pressure at the boundary was solved using continuity conditions along the boundary normal. Reflection and refraction of shock waves from a solid-water interface were also included in the model. With this model, the impact pressure at the solid boundary and the stress, strain as well as velocity discontinuities at the propagating shock fronts were calculated. A comparison with results from previous studies shows that this model provides a more complete and general solution for the jet impact problem. PMID- 8354759 TI - Propagation of shock waves in elastic solids caused by cavitation microjet impact. II: Application in extracorporeal shock wave lithotripsy. AB - To better understand the mechanism of stone fragmentation during extracorporeal shock wave lithotripsy (ESWL), the model developed in Part I [P. Zhong and C.J. Chuong, J. Acoust. Soc. Am. 94, 19-28 (1993)] is applied to study cavitation microjet impingement and its resultant shock wave propagation in renal calculi. Impact pressure at the stone boundary and stress, strain at the propagating shock fronts in the stone were calculated for typical ESWL loading conditions. At the anterior surface of the stone, the jet induced compressive stress can vary from 0.82 approximately 4 times that of the water hammer pressure depending on the contact angles; whereas the jet-induced shear stress can achieve its maximum, with a magnitude of 30% approximately 54% of the water hammer pressure, near the detachment of the longitudinal (or P) wave in the solid. Comparison of model predictions with material failure strengths of renal calculi suggests that jet impact can lead to stone surface erosion by combined compressive and shear loadings at the jet impacting surface, and spalling failure by tensile forces at the distal surface of the stone. Comparing responses from four different stone types suggests that cystine is the most difficult stone to fragment in ESWL, as observed from clinical experience. PMID- 8354760 TI - Air pressure regulation during speech production. AB - Vocal tract pressures during speech tend to be maintained in the face of airway leaks that might be encountered by individuals with repaired palatal clefts. This study tested the hypothesis that such constant pressures can be explained as a consequence of constant pressure source characteristics of the respiratory system during speech production. This conceptualization differs from pressure regulation theories [e.g., D. Warren, Cleft Palate J. 23, 251-260 (1986)] which posit that active reflexive compensatory responses occur to regulate air pressure during speech. Four experiments were conducted to (a) confirm the distinction between constant flow versus constant pressure sources using a plastic vocal tract model, (b) compare air pressure and flow patterns associated with airway leaks in normal speakers to model data, (c) study the effects of gas density in the vocal tract model on air pressure and air flow patterns predicted by a nonreflexive constant pressure source hypothesis, and (d) compare air pressure and air flow patterns associated with airway leaks obtained from normal speakers using different gas densities to model data. Overall, observed flow and pressure patterns suggest the possible influence of constant pressure source characteristics of the respiratory system during speech on maintenance of intraoral air pressure. PMID- 8354761 TI - Response latency, latency-based receiver-operating characteristics, and uncertainty about interaural phase in the detection of in-phase and out-of-phase tones presented in noise. AB - Subjects were given the task of detecting tonal signals presented in a continuous background of white noise which was always in phase at the ears (No). The signals were either in phase (So), or phase-reversed (S pi) at the ears. The analysis of response latencies (for similar levels of performance) indicated that there were consistent differences in the processing of the two types of signals. Latencies were longer, and somewhat more variable, for S pi than for So signals. It was also found that the theory of signal detectability can contribute to an understanding of what and how decisions are made. Latencies were treated as confidence ratings in order to determine latency-based receiver operating characteristics (LROCs) for the detection task. It was observed that the LROCs for the interaural condition No-So tend to leave the origin at a steeper angle than do those for the interaural condition No-S pi, presumably reflecting the different sensory and decision processes employed in the two conditions. When the two interaural conditions were intermixed within blocks of trials, performance was slightly impaired in comparison to the situation in which the interaural condition remained constant throughout blocks of trials. PMID- 8354762 TI - Adaptation of suppression as an explanation of enhancement effects. AB - Delaying the onset of a signal relative to the onset of a simultaneous notched masker often improves the ability of subjects to "hear out" the signal at both threshold and suprathreshold levels. Viemeister and Bacon [J. Acoust. Soc. Am. 71, 1502-1507 (1982)] suggested that such signal-enhancement effects might be attributable to adaptation of the suppression directed from the masker to the signal, thereby releasing the signal from suppression. In support of their hypothesis, Viemeister and Bacon reported that a masker, preceded by an enhancer having no component at the signal frequency, produced more forward masking than did the masker by itself. Here the masker enhancement described by Viemeister and Bacon, signal enhancement, and two-tone suppression were measured in the same six subjects. Parametric manipulations of the masker-enhancement stimulus produced results similar to those previously reported for parallel investigations of signal enhancement, indicating that the two types of enhancement are closely related effects. Although the present data reveal an inverse relationship between the amounts of suppression and enhancement, suggesting that the two processes may be interrelated, no support was obtained for the hypothesis that adaptation of suppression can account for enhancement. PMID- 8354763 TI - Psychoacoustics of normal adult chickens: thresholds and temporal integration. AB - Three adult female chickens were trained to detect pure tones using a positive reinforcement paradigm. A modified perometer estimation-through sequential testing (PEST) threshold determination procedure was used to measure the audiogram between 250 and 5500 Hz, at 0.1-octave steps over most of the range. For the mean audiogram, threshold increased rapidly below 400 Hz and above 4000 Hz. Between these extremes was a broad low threshold area where thresholds varied between 11 and 23 dB, with the lowest thresholds between 1000 and 2000 Hz. Audiograms were similar for all three subjects over the middle of the frequency range, but there was more variability across subjects at the extreme high and low frequencies. After determination of the audiogram, thresholds for 12 frequencies were measured as a function of stimulus duration (ranging from 16 to 750 ms) to determine a threshold-duration function. Average time constants varied from 148 to 348 ms, increasing with increasing stimulus frequency. Average slopes varied from 2.18 dB per doubling of duration to 2.61 dB per doubling of duration, increasing with increasing stimulus frequency. The increases in slope and time constant with stimulus frequency, while consistent, were small compared to the variability of these parameters across subjects. PMID- 8354764 TI - Temporal and spectral basis of the features perceived in repeated noise. AB - When a half-second segment of a noise is played repeatedly, it initially creates a "whooshing" perception. With longer listening, however, individual features like "clanks" and "rasping" emerge. It is easy to tap the period of the perceived structure. This offers a possibility to investigate the mechanisms underlying the perception of these distinct features. The present study addresses the subject of the temporal and spectral extent of the physical correlates of these percepts. Five subjects participated in this study, and their tapping is in notable, although not perfect correlation. The physical correlate of the features can be confined in time to intervals as small as 100 ms. This segment of the stimulus is processed largely independently from the rest of the noise sample. Spectral processing is, in general, local. Some features, however, are spread over more than one octave. In 3 cases out of 25, across-channel processing is apparent. PMID- 8354765 TI - Combined evaluation of interaural time and intensity differences: psychoacoustic results and computer modeling. AB - The physical and the psychophysical relationships between interaural time and intensity differences were studied for 24 frequency bands of critical bandwidth covering the full audio range. For the physical investigations a catalogue of outer ear impulse responses for 122 directions of the upper hemisphere was analyzed according to the combinations of interaural time and level differences found in each critical band. From these data curves of "natural combinations" of the interaural parameter differences were determined by the minimum square error method. In a psychoacoustical study it is shown that signals containing "natural" parameter combinations produce response patterns that differ from those produced when signals with contradictory interaural properties have been used. Finally an extension to the powerful binaural model of Lindemann [J. Acoust. Soc. Am. 80, 1608-1622 (1986)] is introduced, taking into account the results of the previous investigations. PMID- 8354766 TI - Moclobemide: a reversible MAO-A-inhibitor showing weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group. AB - Antidepressant and unwanted effects of moclobemide (400 mg/day) and clomipramine (150 mg/day) were compared in a double-blind, randomised, in-patient, fixed-dose study with weekly ratings and drug level measurements. After 1 week of single blind placebo treatment, 115 patients with major depression fulfilled the criterion of a Hamilton Depression Scale (17-item, HDS) score of > or = 18 and were started on active treatment for 6 weeks. Drop-outs on moclobemide (n = 20) were in particular due to worsening and suicidality (n = 9) whereas drop-outs on clomipramine (n = 12) in particular were due to side effects/adverse events (n = 6) and no drop-outs due to worsening. End-point analysis on the basis of different depression ratings showed consistently a significantly weaker effect of moclobemide (final median HDS: 15) compared with clomipramine (final median HDS: 11). The difference involved both sleep and depression symptoms. These results are generally at variance with the main body of literature on moclobemide, although a higher frequency of drop-out due to worsening in moclobemide-treated patients compared to tricyclic antidepressant-treated patients has been reported in several studies. PMID- 8354767 TI - The sources of convergence between measures of apathy and depression. AB - Apathy and depression are discriminable but related dimensions of behavior. The purpose of this study was to evaluate the source of the overlap between measures of apathy and depression. We evaluated the intercorrelations between the Apathy Evaluation Scale (AES) and the Hamilton Rating Scale for Depression (HamD) in 107 subjects, aged 53-85, who met research criteria for normal aging, left or right cerebral hemisphere stroke, probable Alzheimer's disease, or major depression. We determined the correlation between the individual items on the HamD and the total scores on the AES and the HamD. The HamD items having the strongest correlations with AES total score were diminished work/interest, psychomotor retardation, anergy, and lack of insight. The correlation between AES and HamD total scores was nonsignificant when major depression subjects and these variables most closely related to apathy were excluded from consideration. These findings indicate that the convergence between HamD and AES is attributable to (i) a subset of HamD items which are consistent with the syndrome of apathy and (ii) the fact that major depression is associated with both apathy and depression. Clinical and research applications of these results are discussed. PMID- 8354768 TI - Response of psychotic depression subtypes to pharmacotherapy. AB - Patients with psychotic depression respond well when treated with a combination of an antidepressant and antipsychotic medication. We previously reported that they will respond in a similar fashion when treated with amoxapine monotherapy. There are few prospective studies on the pharmacologic treatment response of psychotic depression subtypes. We treated 37 inpatients, 21 with mood congruent (MC) psychotic depression and 16 with mood incongruent (MI) psychotic depression, in a randomized double-blind fashion with either the combination of amitriptyline and perphenazine or with amoxapine for 4 weeks. Depression and psychosis ratings improved in a similar manner in both the MC or MI patients irrespective of medication treatment group. Global response rates were similar in the MI patients and MC patients. The data suggest that classifying psychotic depression into MC versus MI subtypes may have limited acute prognostic value in pharmacotherapy response rates. PMID- 8354769 TI - 48-hour rapid cycling: results of psychopathometric, polysomnographic, PET imaging and neuro-endocrine longitudinal investigations in a single case. AB - We report a 64-year-old patient suffering from rapid cycling bipolar disorder who was studied by means of polysomnography, neuroendocrine tests and PET (positron emission tomography) imaging. In a manner only partly compatible with the cholinergic-aminergic imbalance model of mania and depression, a linkage of REM sleep disinhibition and depressive mood was observed, but no decisive REM sleep delay was seen on manic days. Growth hormone secretion after clonidine stimulation was blunted on depressive and hypomanic days. A series of total sleep deprivations led to a positive effect on psychopathology for about two weeks. Carbamazepine treatment normalized REM sleep variables, damped the amplitude of mood cycling of the patient, increased TSH and decreased FT4. PMID- 8354770 TI - A new sampling strategy for linkage studies in psychoses. AB - Linkage between stuttering and manic-depression has been postulated to account for the reported association between these conditions, in three large pedigrees. This finding permits a novel and potentially more productive sampling strategy to be used in future linkage studies. PMID- 8354771 TI - A study comparing paroxetine placebo and imipramine in depressed patients. AB - These data provide evidence for the antidepressant efficacy of paroxetine. Paroxetine- and imipramine-treated patients were significantly different from placebo-treated patients, but little different to each other, on all depressive outcome measures. However, paroxetine appeared to have a possibly greater and earlier beneficial effect on anxiety symptoms associated with depression, when compared with imipramine. Both active therapies were effective in treating patients with severe depression. Side effects for paroxetine were typical of other serotonin (5-HT) uptake inhibitors but different from those of imipramine. In particular, anticholinergic and cardiovascular symptoms were reduced, and premature withdrawal less likely. PMID- 8354772 TI - Specificity of mixed affective states: clinical comparison of dysphoric mania and agitated depression. AB - To investigate the clinical specificity of mixed affective states, we compared clinical characteristics of mixed (dysphoric) manics to those of agitated depressed patients. The subjects were inpatients studied in the NIMH Clinical Research Branch Collaborative Study on the Psychobiology of Depression, Biological Studies. Behavior and symptom ratings for depressive and manic symptoms were obtained during a 15-day placebo washout period. Patients with agitated depression were compared to those in acute manic episodes with and without prominent depressive symptoms. Mania ratings clearly distinguished agitated depressed from mixed manic patients. Concerning depression and general psychopathology, mixed manics had more severe agitation, hostility and cognitive impairment than did agitated depressed patients. Depressed mood and anxiety did not differ significantly between the two groups. Nurse ratings for depression and anxiety, based on ward behavior, were similar for mixed manics and agitated depressed patients, while physician-interview rated depression and anxiety were higher in agitated depressed patients. These data support the existence of superimposed depressive and manic syndromes in mixed manics. PMID- 8354774 TI - One house of dentistry. PMID- 8354773 TI - Brain electrical activity in depression described by equivalent dipoles. AB - The majority of neurophysiological investigations of waking EEG in depression have been relatively disappointing. Since the topographic distribution of brain electrical activity over the scalp in the frequency domain (FFT-power) varies considerably when choosing another site for the reference, it is not surprising that various investigators reported contradictory results. The aim of the present study was to investigate differences in brain electrical activity in a sample of depressed patients as compared to healthy subjects using a newly developed method called FFT approximation. As the major finding healthy subjects and depressed patients demonstrated significantly divergent patterns of localization between frequency bands in the anterior-posterior direction. The investigation suggests that a non-invasive neurophysiological methods gives results which are comparable to those obtained by other functional and structural imaging methods in depressive illness. PMID- 8354775 TI - Bonding amalgams. PMID- 8354776 TI - A noteworthy study. PMID- 8354777 TI - Implants revisited. PMID- 8354778 TI - Checking anti-retraction valves. PMID- 8354779 TI - A flawed study on TM? PMID- 8354781 TI - AIDS cited as no. 1 health concern. PMID- 8354782 TI - Tufts' study aims to save cancer patients' salivary glands. PMID- 8354780 TI - What the experts know. PMID- 8354783 TI - Managing medical emergencies. AB - A simple dental procedure can quickly escalate into a medical emergency. Management of six common emergencies is described. PMID- 8354784 TI - Dental office emergencies: do you know your legal obligations? PMID- 8354785 TI - Dental office compliance evaluation for the OSHA Bloodborne pathogens Standard and Hazard Communication Program. PMID- 8354786 TI - Prevalence of upper extremity neuropathy in a clinical dentist population. AB - When asked about altered sensation in hands or arms, forearms, cervical area or neck, 29 percent of Nebraska dentists surveyed said they felt pain, followed by numbness and tingling. The prevalence suggests the possibility of an occupational concern. PMID- 8354787 TI - Managing obstructive sleep apnea. AB - Obstructive sleep apnea, cessation of breathing during sleep, is potentially life threatening and requires prompt intervention. A prosthesis can reposition the mandible during sleep and minimize or prevent the tongue from collapsing against the pharynx. Two case reports discuss the effectiveness of prosthetic devices. PMID- 8354789 TI - Educating patients: a new necessity. PMID- 8354788 TI - HIV-related neuropsychiatric changes: concerns for dental professionals. AB - HIV infection can cause a variety of neuropsychiatric changes. These changes and their effects on dental care delivery are discussed. A case report illustrates the behavioral changes of one patient. PMID- 8354790 TI - Medicare: trends in reimbursing hospital dental practices. AB - A survey of dentists working in hospitals found that dental procedures covered under Medicare are not equally reimbursed. Lack of uniform guidelines, appropriate interpretation and universal claim forms lead to problems. Most respondents favor medically adjunctive dental care in the national health care reform. PMID- 8354791 TI - The patient's health history form: how healthy is it? AB - An aging population, a more medically complex patient base and concerns about infectious diseases have complicated dentistry in the past decade--making a thorough health history more important than ever. A survey comparing dental university health history forms with those used by some general practitioners is presented. PMID- 8354792 TI - Acute effect of cigarette smoking on the coronary circulation: constriction of epicardial and resistance vessels. AB - OBJECTIVES: This study was performed to determine the acute effect of cigarette smoking on proximal and distal epicardial conduit and coronary resistance vessels. BACKGROUND: Cigarette smoking causes constriction of epicardial arteries and a decrease in coronary blood flow in patients with coronary artery disease, despite an increase in myocardial oxygen demand. The role of changes in resistance vessel tone in the acute coronary hemodynamic effect of smoking has not been examined. METHODS: Twenty-four long-term smokers were studied during cardiac catheterization after vasoactive medications had been discontinued. The effect of smoking one cigarette 10 to 15 mm long on proximal and distal conduit vessel segments was assessed before and immediately after smoking and at 5, 15 and 30 min after smoking (n = 8). To determine the effect of smoking on resistance vessels, coronary flow velocity was measured in a nonobstructed artery with a 3F intracoronary Doppler catheter before and for 5 min after smoking (n = 8). Eight patients were studied without smoking to control for spontaneous changes in conduit arterial diameter (n = 5) and resistance vessel tone (n = 3). RESULTS: The average diameter of proximal coronary artery segments decreased from 2.56 +/- 0.12 mm (mean +/- SEM) before smoking to 2.41 +/- 0.09 mm 5 min after smoking (-5 +/- 2%, p < 0.05). Distal coronary diameter decreased from 1.51 +/- 0.07 to 1.39 +/- 0.06 mm (-8 +/- 2%, p < 0.01). Marked focal vasoconstriction after smoking was observed in two patients. Coronary diameter returned to baseline by 30 min after smoking. There was no change in vessel diameter in control patients. Despite a significant increase in the heart rate-mean arterial pressure product, coronary flow velocity decreased by 7 +/- 4% (p < 0.05) and coronary vascular resistance increased by 21 +/- 4% (p < 0.01) 5 min after smoking. There was no change in these variables in the control subjects. CONCLUSIONS: Smoking causes immediate constriction of proximal and distal epicardial coronary arteries and an increase in coronary resistance vessel tone, despite an increase in myocardial oxygen demand. These acute coronary hemodynamic effects may contribute to the adverse cardiovascular consequences of cigarette smoking. PMID- 8354793 TI - Smoking-induced coronary vasoconstriction: implications for therapeutic use of nicotine. PMID- 8354794 TI - Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease. AB - OBJECTIVES: The aim of this study was to investigate coronary vasodilator reserve and metabolism in myocardium subtended by angiographically normal arteries remote from ischemia. BACKGROUND: After infarction, structural and functional changes occur in remote myocardium often subtended by normal arteries. Whether changes occur in regions remote from ischemic but noninfarcted myocardium is unknown. METHODS: Coronary vasodilator reserve was measured with positron emission tomography in 12 patients with single-vessel disease using intravenous dipyridamole (0.56 mg/kg for 4 min). In another 10 patients, simultaneous arterial/great cardiac vein catheterization was performed during atrial pacing to measure myocardial metabolism in regions subtended by diseased or normal arteries. RESULTS: Basal myocardial blood flow in stenosis-related regions was comparable to that in remote regions but was lower after dipyridamole administration (1.73 +/- 0.91 vs. 2.89 +/- 0.93 ml/min per g, p < 0.01), giving coronary vasodilator reserve values of 1.80 +/- 0.82 and 2.73 +/- 0.89 (p < 0.01). In normal control subjects, basal myocardial blood flow was 0.92 +/- 0.13 and 3.67 +/- 0.94 ml/min per g in the basal state and after dipyridamole (both p < 0.05 vs. values in remote regions), and coronary vasodilator reserve was 4.07 +/- 0.98 (p < 0.01) vs. values in remote regions). During pacing there was net lactate release in diseased regions (-18 +/- 27%, p < 0.05 vs. values in remote regions and control subjects) and extraction in remote regions (38 +/- 17%) and in normal control subjects (26 +/- 11%). Glucose and alanine extraction were increased in diseased (8 +/- 6% and 6 +/- 6%) and remote regions (6 +/- 3% and 4 +/- 3%), compared with values in normal control subjects (2 +/- 3% and -1 +/- 3%, both p < 0.05 vs. diseased and remote regions). CONCLUSIONS: Coronary vasodilator reserve is reduced and glucose and alanine metabolism is abnormal in regions subtended by normal arteries remote from ischemic but noninfarcted myocardium. PMID- 8354795 TI - Abnormal systolic blood pressure response during exercise recovery in patients with angina pectoris. AB - OBJECTIVES: This study was conducted to clarify the mechanisms of the abnormal systolic blood pressure response after exercise in patients with angina pectoris. BACKGROUND: An abnormal systolic blood pressure response in patients with angina pectoris has been observed not only during exercise but also during the recovery period after exercise. However, the mechanisms of this abnormal response during recovery have not been elucidated. METHODS: Thirty-five patients with angina pectoris and 17 control subjects underwent bicycle ergometric studies after insertion of a Swan-Ganz catheter. RESULTS: In control subjects, all hemodynamic variables decreased rapidly after exercise. In 7 of the 35 patients, systolic blood pressure increased after exercise. The patients with angina were classified into two groups. In group I (17 patients), changes in systolic blood pressure during recovery were smaller than those in control subjects. In group II (18 patients) recovery of systolic blood pressure was normal. Changes in stroke index from rest to peak exercise were smaller in group I than in group II. Stroke index in both patient groups increased paradoxically during recovery. The increase in systemic vascular resistance index during recovery and the ratio of plasma norepinephrine concentration to cumulative work load were greater in group I than in group II. CONCLUSIONS: An abnormal systolic blood pressure response after physical exercise in patients with angina pectoris is indicative of severe myocardial ischemia during exercise and may be caused by an increase in stroke volume due to recovery from myocardial ischemia and increased systemic vascular resistance secondary to exaggerated sympathetic nervous activity. PMID- 8354796 TI - Independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in coronary artery disease. AB - OBJECTIVES: The objective of this study was to examine the independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in patients with angiographically defined coronary artery disease. BACKGROUND: Previous studies showed the importance of exercise thallium-201 in risk stratification. However, most of these studies used planar imaging techniques. METHODS: Follow-up data were obtained in 316 medically treated patients with coronary artery disease. Cox proportional hazards regression models were used to examine the independent and incremental prognostic values of clinical, exercise, thallium and cardiac catheterization data. RESULTS: There were 35 events (cardiac death or nonfatal myocardial infarction) at a mean follow-up time of 28 months. Univariate analysis showed that gender (chi-square = 5.1), exercise work load (chi-square = 3.1), extent of coronary artery disease and left ventricular ejection fraction (chi-square = 14.8) and thallium variables (chi-square = 22.7) were prognostically important. The thallium data provided incremental prognostic value to catheterization data (chi-square = 33.7, p < 0.01). The extent of the perfusion abnormality was the single best predictor of prognosis (chi-square = 14). Patients with a large perfusion abnormality had a worse prognosis than that of patients with a mild or no abnormality (Mantel-Cox statistics = 10.6, p < 0.001). CONCLUSIONS: In medically treated patients with coronary artery disease, exercise SPECT thallium imaging provides independent and incremental prognostic information even when catheterization data are available. The extent of the perfusion abnormality is the single most important prognostic predictor. PMID- 8354797 TI - Ischemic threshold during two exercise testing protocols and during ambulatory electrocardiographic monitoring. AB - OBJECTIVES: The aim of this study was to examine the dependence of the ischemic threshold during exercise testing on the exercise protocol employed and to determine the relation between the ischemic thresholds observed during exercise and during daily activity. BACKGROUND: The ischemic threshold (heart rate at 1-mm ST segment depression) during daily activity has been reported to be lower than that observed during exercise testing. Recent reports have hypothesized that this difference is probably dependent on the exercise protocol employed. METHODS: Twenty-two patients with known coronary artery disease, not receiving antianginal medications, were evaluated by repeated exercise testing according to the Bruce and the modified Davidson protocols and by 48-h ambulatory electrocardiographic monitoring. RESULTS: Although the heart rate at 1-mm ST segment depression was somewhat lower with the Davidson than with the Bruce protocol (112 +/- 14 vs. 115 +/- 14 beats/min), the rate-pressure product at 1-mm ST segment depression was similar during the two protocols (16,900 +/- 4,000 vs. 17,700 +/- 3,600). The mean heart rate (100 + 12 beats/min) at 1-mm ST segment depression during ambulatory ischemic episodes (n = 137) was significantly lower than that observed during both exercise protocols (p < 0.001 for both comparisons). CONCLUSIONS: Exercise-induced ischemia occurs at a relatively fixed threshold that is mainly dependent on myocardial oxygen demand and is independent of the exercise protocol employed. Ischemia on ambulatory monitoring, however, occurs at a much more variable threshold that is commonly lower than that observed during exercise and is therefore dependent on other factors in addition to increased demand. PMID- 8354799 TI - Verapamil and aspirin modulate platelet-mediated vasomotion in arterial segments with intact or disrupted endothelium. AB - OBJECTIVES: This study was designed to examine the effects of verapamil and aspirin, which decrease thromboxane A2 and serotonin release, on the modulation of vascular tone by platelets. BACKGROUND: Aggregating platelets cause constriction of de-endothelialized arterial segments through thromboxane A2 and serotonin release. These cells cause relaxation of arterial segments with intact endothelium through release of the endothelium-derived relaxing factor. METHODS: Healthy subjects were given either no drug, verapamil or aspirin for > or = 5 days before their platelets were obtained. The effects of platelets obtained from subjects before and after treatment with aspirin or verapamil on the tone of rat aortic rings were determined. RESULTS: As expected, control platelets (before verapamil or aspirin treatment) induced concentration-dependent relaxation of rat aortic rings with intact endothelium and a concentration-dependent contraction of de-endothelialized rings. Verapamil treatment enhanced (p < 0.02) the platelet mediated relaxation in rings with intact endothelium and abolished platelet mediated constriction (p < 0.01) in the de-endothelialized rings. Aspirin treatment also abolished (p < 0.05) platelet-mediated constriction of the de endothelialized rings. The de-endothelialized rings contracted normally in response to the synthetic thromboxane A2 analogue U46,619, as well as to serotonin, indicating that the vascular smooth muscle response to thromboxane A2 and serotonin was intact. CONCLUSIONS: This study provides evidence for the modulation of platelet-mediated vasoconstriction of de-endothelialized arterial segments by prior treatment of subjects with verapamil or aspirin. In clinical syndromes characterized by endothelial dysfunction or disruption, treatment with verapamil or aspirin may modify platelet-vessel wall interactions. PMID- 8354798 TI - Benefits of cardiac rehabilitation and exercise training in secondary coronary prevention in the elderly. AB - OBJECTIVES: The aim of this study was to determine the effects of cardiac rehabilitation and exercise training on plasma lipids, indexes of obesity and exercise capacity in the elderly and to compare the benefits in elderly patients with coronary heart disease with benefits in a younger cohort. BACKGROUND: Despite the well proved benefits of cardiac rehabilitation and exercise training, elderly patients with coronary heart disease are frequently not referred or vigorously encouraged to pursue this therapy. In addition, only limited data are available for these elderly patients on the benefits of cardiac rehabilitation on plasma lipids, indexes of obesity and exercise capacity. METHODS: At two large multispecialty teaching institutions, baseline and post-rehabilitation data including plasma lipids, indexes of obesity and exercise capacity were compared in 92 elderly patients (> or = 65 years, mean age 70.1 +/- 4.1 years) and 182 younger patients (< 65 years, mean 53.9 +/- 7.4 years) enrolled in phase II cardiac rehabilitation and exercise programs after a major cardiac event. RESULTS: At baseline, body mass index (26.0 +/- 3.9 vs. 27.8 +/- 4.2 kg/m2, p < 0.001), triglycerides (141 +/- 55 vs. 178 +/- 105 mg/dl, p < 0.01) and estimated metabolic equivalents (METs) (5.6 +/- 1.6 vs. 7.7 +/- 3.0, p < 0.0001) were lower and high density lipoprotein cholesterol was greater (40.4 +/- 12.1 vs. 37.5 +/- 10.4 mg/dl, p < 0.05) in the elderly than in younger patients. After rehabilitation, the elderly demonstrated significant improvements in METs (5.6 +/ 1.6 vs. 7.5 +/- 2.3, p < 0.0001), body mass index (26.0 +/- 3.9 vs. 25.6 +/- 3.8 kg/m2, p < 0.01), percent body fat (24.4 +/- 7.0 vs. 22.9 +/- 7.2%, p < 0.0001), high density lipoprotein cholesterol (40.4 +/- 12.1 vs. 43.0 +/- 11.4 mg/dl, p < 0.001) and the ratio of low density to high density lipoprotein cholesterol (3.6 +/- 1.3 vs. 3.3 +/- 1.0, p < 0.01) and a decrease in triglycerides that approached statistical significance (141 +/- 55 vs. 130 +/- 76 mg/dl, p = 0.14) but not in total cholesterol or low density lipoprotein cholesterol. Improvements in functional capacity, percent body fat and body mass index, as well as lipids, were statistically similar in the older and younger patients. CONCLUSIONS: Despite baseline differences, improvements in exercise capacity, obesity indexes and lipids were very similar in older and younger patients enrolled in cardiac rehabilitation and exercise training. These data emphasize that elderly patients should not be categorically denied the psychosocial, physical and risk factor benefits of secondary coronary prevention including formal cardiac rehabilitation and supervised exercise training. PMID- 8354800 TI - Failed direct coronary angioplasty for acute myocardial infarction: in-hospital outcome and predictors of death. AB - OBJECTIVES: The purpose of this study was to compare the mechanisms, predictors and outcome of patients with failed direct coronary angioplasty of the infarct related artery with those in patients with successful direct angioplasty. BACKGROUND: Direct coronary angioplasty of the infarct-related artery, without antecedent thrombolytic therapy, is an effective treatment for patients with acute myocardial infarction. Concern has been expressed over high mortality rates in patients with failed direct infarct angioplasty. METHODS: All patients treated by angioplasty were prospectively entered into a computer data base. The characteristics and outcome of all patients with failed direct angioplasty were reviewed and compared with those of patients with successful direct angioplasty. RESULTS: Direct angioplasty was successful in 705 (94%) of 750 patients and unsuccessful in 45 (6%). Patients in the failure group were more likely to be in cardiogenic shock (22% vs. 7%, p < 0.003), to have had a previous myocardial infarction (44% vs. 28%, p < 0.03) and to have three-vessel coronary artery disease (44% vs. 23%, p < 0.003). Age, gender, ejection fraction, previous bypass surgery and diabetes mellitus were similar in both groups. Only the presence of multivessel coronary artery disease (p < 0.004) and cardiogenic shock (p < 0.025) were independent predictors of failed direct angioplasty. In-hospital death (31% vs. 4.8%, p < 0.001) and the need for emergency coronary artery bypass surgery (27% vs. 0.5%, p < 0.0001) were more frequent in patients with unsuccessful than in patients with successful direct angioplasty. Patients with failed direct angioplasty and in-hospital death usually had multiple high risk characteristics, including cardiogenic shock (50%), previous myocardial infarction (43%) and multivessel coronary artery disease (93%). CONCLUSIONS: Direct coronary angioplasty is an effective method for establishing reperfusion in acute myocardial infarction. Procedural failure is infrequent, usually occurring in patients with high risk baseline characteristics. PMID- 8354801 TI - Influence of infarct-related artery patency on the indexes of parasympathetic activity and prevalence of late potentials in survivors of acute myocardial infarction. AB - OBJECTIVES: The purpose of this study was to determine whether infarct-related coronary artery patency influences myocardial electrical stability as measured by the prevalence of late potentials or heart rate variability. BACKGROUND: Several studies have suggested that loss of vagal activity is associated with an increased incidence of arrhythmic death after myocardial infarction. METHODS: A short-duration, high resolution electrocardiogram (ECG) was performed before hospital discharge in 175 patients with a first myocardial infarction. Seventy three patients received thrombolytic therapy. All patients underwent coronary angiography. Coronary occlusion was defined as minimal or no anterograde flow. Eighty-eight patients (50.3%) had an occluded infarct-related artery. Sixty-two healthy subjects served as control subjects to determine the normal range of heart rate variability. RESULTS: Comparison between the control group and patients without patency of the infarct-related artery in the time domain and spectral analyses revealed in the latter patients a reduced heart rate variability (p < 0.0001) and a lower power spectrum density in both the 0.05- to 0.15-Hz band (p < 0.0001) and the 0.15- to 0.35-Hz band (p < 0.0001). The heart rate variability in patients with late potentials was lower than in those with a normal signal-averaged ECG. Those patients with spontaneous or thrombolysis induced reperfusion have less occurrence of late potentials and higher parasympathetic activity than do patients with a closed artery. CONCLUSIONS: This study suggests that the patency of the infarct-related artery determines both the absence of late potentials and the preservation of vagal tone and may explain the reduction in mortality induced by thrombolytic therapy in myocardial infarction. PMID- 8354802 TI - Significance of diabetes mellitus in patients with acute myocardial infarction receiving thrombolytic therapy. Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. AB - OBJECTIVES: The purpose of this study was to evaluate the risks and benefits associated with thrombolytic therapy in patients with diabetes presenting with acute myocardial infarction. BACKGROUND: Diabetes mellitus is associated with adverse risk factors and a hypercoagulable state that may adversely affect the outcome of thrombolytic therapy. METHODS: Data were analyzed from 8,055 of the 8,239 patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue Plasminogen Activator/Streptokinase Mortality trial (diabetes history was missing for 184 patients). RESULTS: There were 883 patients with and 8,272 patients without diabetes. Among the diabetic patients, 160 were receiving insulin therapy. Baseline risk factors were significantly worse in diabetic patients, who were older and had a higher rate of previous infarction and antecedent angina and a higher Killip grade at admission. Bleeding and hemorrhagic and ischemic stroke rates were similar among diabetic and nondiabetic patients. Hospital and 6-month mortality rates were highest among diabetic patients receiving insulin therapy (16.9% and 23.1%, respectively), followed by diabetic patients not receiving insulin therapy (11.8% and 17.8%), and lowest in nondiabetic patients (7.5% and 10.7%, p < 0.0001). Whereas diabetes of 5 years' duration was associated with a mortality rate similar to that of nondiabetic patients, a > 5-year duration was associated with a relative mortality risk of 1.38 (95% confidence interval [CI] 0.88 to 2.15) and a > 10-year duration with a relative mortality risk of 1.99 (95% CI 1.40 to 2.81). The independent relative risk for incremental mortality from discharge to 6 months was 1.74 (95% CI 1.21 to 2.50). Mortality rate among diabetic patients was lowest in patients who received both streptokinase and heparin (9.8% vs. 16.1% in patients who received streptokinase but no heparin, p < 0.05). CONCLUSIONS: The relative mortality of diabetic versus nondiabetic patients was similar to that observed in previous studies of patients with myocardial infarction not receiving thrombolytic therapy, indicating that mortality in diabetic patients receiving thrombolytic therapy is reduced to the same extent as in nondiabetic patients. In addition, risk of bleeding and stroke was not increased, indicating that diabetic patients can safely receive thrombolytic therapy for the same indications as nondiabetic patients. PMID- 8354803 TI - Effect of thrombolysis on acute mitral regurgitation during evolving myocardial infarction. Experience from the Thrombolysis in Myocardial Infarction (TIMI) Trial. AB - OBJECTIVES: This study was undertaken to determine whether early successful thrombolysis can reverse infarct-associated mitral valve dysfunction. BACKGROUND: Mitral regurgitation is a common complication of acute myocardial infarction and has been shown to adversely affect both short- and long-term prognosis. Although anecdotal reports have suggested that reperfusion of the infarct-related artery may restore normal function to the mitral valve, this theory has not been subjected to formal investigation. METHODS: Patients with total or partial obstruction of the infarct-related artery received intravenous thrombolytic therapy with either streptokinase or recombinant tissue-type plasminogen activator within 7 h of symptom onset (mean 4.8 h) as part of the Thrombolysis in Myocardial Infarction (TIMI) Phase I trial. Repeat coronary angiography assessed arterial patency at 90 min and 10 days after attempted reperfusion. The presence and severity of mitral regurgitation were determined by contrast ventriculography both before thrombolysis and before hospital discharge. RESULTS: Overall, 21 (16%) of the 132 study patients exhibited mitral regurgitation on either their initial or their predischarge ventriculogram. The proportion of infarct-related arteries found to be patent (TIMI flow grade 2 or 3) was statistically similar in patients with and without mitral regurgitation during each angiographic evaluation period (initial, 90 min and 10 days). Although coronary artery perfusion increased overall during sequential measurement (mean TIMI grade was 0.4 +/- 0.6 initially, 1.5 +/- 1.3 at 90 min and 2.2 +/- 1.0 at 10 days), the pattern of reperfusion observed could not predict an increase or decrease in regurgitant severity (p = NS). Early mitral regurgitation resolved in 57% of patients by 10 days, but this resolution appeared independent of the presence or absence of improved coronary perfusion (60% vs. 50%). The development of new regurgitation during the recovery period (6%) was also unrelated to improved perfusion (7% vs. 4%). CONCLUSIONS: Acute mitral regurgitation developing during myocardial infarction shows frequent changes in its presence or severity during the 1st 10 days, appears independent of coronary artery patency both early and late after thrombolysis and cannot be reliably treated by improving arterial perfusion with thrombolytic agents. PMID- 8354804 TI - Cardiac rupture, a clinically predictable complication of acute myocardial infarction: report of 70 cases with clinicopathologic correlations. AB - OBJECTIVE: To test the hypothesis that certain clinical events may precede free wall myocardial rupture and allow its prediction, we conducted a retrospective and prospective study of 70 patients with rupture. BACKGROUND: Rupture of the left ventricular free wall develops in approximately 10% of patients with fatal acute transmural myocardial infarction. Clinically, its occurrence has been considered precipitous and unexpected. Pathologically, however, rupture appears to be a stuttering, progressive process characterized in many instances by an infiltrating intramural hemorrhage and a thrombus within the tear of > or = 1 day's duration. METHODS: The clinical course and evolutionary electrocardiographic (ECG) changes in 70 consecutive patients with rupture and 100 comparison patients with acute myocardial infarction but without rupture were reviewed to ascertain whether certain clinical symptoms, signs and ECG alterations occur in patients prone to develop rupture, allowing its anticipation. In addition, a correlation was established between the site of infarction indicated by the ECG and the site of rupture determined at autopsy or surgery. RESULTS: Patients with rupture had a significantly greater incidence of pericarditis, repetitive emesis and restlessness and agitation than did patients without rupture. More than 80% of patients with rupture had two or more symptoms compared with 3% of patients without rupture (p < 0.002). A deviation from the expected evolutionary T wave pattern occurred in 94% of patients with rupture and 34% of control patients (p < or = 0.02). An abrupt transient episode of hypotension and bradycardia, probably due to the initial tearing of the epicardium with a resultant small hemopericardium, was observed in 21% of patients with rupture. Rupture of the midlateral wall was most common (32%) and usually occurred in the setting of an inferoposterolateral infarction related to an acute left circumflex artery occlusion. On the basis of these clinical and ECG changes, rupture was confirmed by echocardiography and pericardiocentesis in the two most recent patients, and the defect was successfully repaired. CONCLUSIONS: Rupture is often preceded by particular symptoms, signs--namely, one or more episodes of abrupt, transient hypotension and bradycardia and unexpected alterations of the T waves, especially directional changes of the latter. Patients displaying these symptoms, signs and ECG changes require a bedside echocardiogram and echocardiographically guided pericardiocentesis if fluid is visualized. If the pericardiocentesis identifies the fluid as blood, immediate surgery is indicated. PMID- 8354805 TI - Percutaneous angioplasty of stenosed gastroepiploic artery grafts. AB - OBJECTIVES: This report describes our early experience and results with percutaneous transluminal coronary angioplasty of gastroepiploic artery grafts in 12 patients. BACKGROUND: Angioplasty has been successfully performed in saphenous vein and internal thoracic artery grafts; however, experience with angioplasty in gastroepiploic artery/coronary artery bypass grafts is limited. METHODS: Balloon angioplasty was performed in 12 patients (11 men, 1 woman; mean age 58 +/- 8 years) with either total occlusion (6 patients) or severe stenosis (6 patients) of a gastroepiploic artery/coronary artery anastomosis. In seven patients, a guide wire/balloon catheter system was used through a 7F sheath inserted into the celiac trunk. In seven patients, including two who had unsuccessful wire/balloon angioplasty, an over the wire system was used through a 6.5F Cobra or 7F JR4 guide catheter, selectively inserted into the gastroduodenal artery. RESULTS: Angioplasty was successful in five (83%) of six patients with stenosis and in one of six patients with total occlusion (p = 0.08, 1 - beta = 0.68). The guide wire could not be advanced through the lesion in five patients, and the balloon catheter did not cross the lesion in one patient whose gastroepiploic artery was tortuous. Catheters exhibited better trackability and pushability when the over the wire system was used, and five of the six successes were achieved using this approach. Follow-up arteriography was performed in five patients, and all of the gastroepiploic artery grafts were patent without stenosis. CONCLUSIONS: Angioplasty can be safely performed in stenosed gastroepiploic artery grafts. An over the wire system that uses a thin balloon catheter inserted through a guide catheter in the gastroduodenal artery seems optimal. PMID- 8354806 TI - Therapeutic end points for the treatment of atrioventricular node reentrant tachycardia by catheter-guided radiofrequency current. AB - OBJECTIVES: The purpose of this prospective study was to test the hypothesis that the elimination of inducible repetitive atrioventricular (AV) node reentry despite the persistence of slow AV pathway conduction is a valid end point for radiofrequency catheter ablation procedures in patients with supraventricular tachycardia due to AV node reentry. BACKGROUND: Although modification of AV node physiology by radiofrequency current can eliminate AV node reentrant tachycardia, therapeutic end points that are definitive of a satisfactory result in patients undergoing modification of the slow AV pathway have not been established. Applications of radiofrequency current at selected sites may eliminate all evidence of slow pathway conduction or sufficiently modify the refractory properties of the slow pathway to preclude sustained arrhythmias. Accordingly, total abolition of dual AV node physiology may not be necessary to prevent arrhythmia recurrence. METHODS: Radiofrequency catheter ablation of the slow AV pathway was attempted in 59 patients with typical AV node reentry. Tissue ablation was performed with a continuous wave of 500-kHz radiofrequency current. Twenty-five to 35 W was applied for 60 s at the site selected for tissue destruction. RESULTS: Dual AV node physiology was eliminated completely in 35 patients (59%), persisted without inducible AV node reentry in 13 patients (22%) and persisted with inducible single AV reentrant beats in 11 patients (19%). In patients with persistent dual AV node physiology, the maximal difference between the effective refractory period of the fast and slow pathways was reduced from 104 +/- 62 ms before the procedure to 37 +/- 37 ms after AV conduction had been modified (p < 0.001). During a mean follow-up interval of 15 months (range 4 to 28), only one patient (2%) had a recurrence of the tachycardia. CONCLUSIONS: Results demonstrate that when complete elimination of dual AV node physiology is difficult, modification of slow pathway conduction to the extent that repetitive AV node reentry cannot be induced is a definitive end point that portends a good prognosis. PMID- 8354807 TI - Safety and efficacy of central intravenous bolus administration of adenosine for termination of supraventricular tachycardia. AB - OBJECTIVES: This study was done to quantify the dosing differences between central and peripheral adenosine administration for treatment of supraventricular tachycardia. BACKGROUND: Earlier studies that evaluated the safety and efficacy of adenosine primarily utilized a peripheral site of administration. Although it has been recommended that lower doses should be given centrally, dosing recommendations have not been provided. METHODS: Thirty adults with supraventricular tachycardia underwent invasive electrophysiologic study and were treated with central and peripheral intravenous administration of adenosine. Peripheral injections were administered through a venous catheter in an upper extremity and central infusions were accomplished by means of a catheter positioned in or near the right atrium. The site of administration was randomized and each subject received adenosine by both routes. Adenosine was administered every minute in increasing increments of 3, 6, 9 and 12 mg until the tachycardia terminated. Peripheral responses were compared with those obtained centrally. RESULTS: The minimal effective peripheral dose was distributed among the four doses: Tachycardia was terminated in 11 patients with 3 mg (37%), in 10 (33%) with 6 mg, in 4 (13%) with 9 mg and in 5 (17%) with 12 mg. In contrast, after central administration, 23 episodes of tachycardia (77%) were terminated with 3 mg, 6 (20%) with 6 mg and 1 (3%) with 9 mg; none required 12 mg. Lower doses of adenosine were more effective after central than after peripheral administration, with 63% of the subjects requiring a lesser dose. There was no difference between the two routes of drug administration in the incidence of side effects or transient arrhythmias at the time of tachycardia termination. CONCLUSIONS: Adenosine can be safely given centrally for termination of supraventricular tachycardia. The initial dose should be 3 mg. PMID- 8354808 TI - Effect of rate and coupling interval on endocardial R wave amplitude variability in permanent ventricular sensing lead systems. AB - OBJECTIVES: We have observed sensing errors in third generation implantable cardioverter-defibrillators that appear to be caused by variation in the R wave amplitude during sinus rhythm, particularly after premature beats. The purpose of this study was to quantify spontaneous R wave variability during sinus rhythm and to determine whether abrupt changes in cycle length further augment R wave amplitude variability. BACKGROUND: Pacemaker sensing algorithms presume a relatively constant R wave signal to establish a sensing threshold. The concept of a fixed sensing threshold is not as applicable in third-generation cardioverter-defibrillators, which depend on automatic gain amplifiers to rapidly detect ventricular fibrillation. These devices may be susceptible to undersensing during sinus rhythm if significant variability in R wave signal characteristics occurs. METHODS: Twelve patients with combination bradycardia pacing cardioverter defibrillators were studied. The device used (Cadence, Ventritex) allowed recording of real time, telemetered electrograms from the sensing lead system. Measurements were made of the maximal range of the R wave amplitude during sinus rhythm and in response to abrupt changes in heart rate produced by premature atrial and ventricular stimuli. RESULTS: The maximal range in R wave amplitude during sinus rhythm was 1.7 +/- 1.3 mV, or 23.7 +/- 19.2% of the mean R wave amplitude. The R wave amplitude variability increased with abrupt changes in cycle length, with a range of 2.8 +/- 1.5 mV, or 38.8 +/- 18.3% of the mean R wave amplitude (p < 0.05 compared with sinus rhythm). In most patients, R wave amplitude and coupling interval demonstrated an inverse proportional relation. CONCLUSIONS: There is substantial variability in the R wave amplitude during sinus rhythm measured by permanent ventricular sensing lead systems, and this variability is further augmented by abrupt changes in cycle length. This phenomenon may explain the occurrence of undersensing of sinus rhythm in implantable cardioverter-defibrillators with automatic gain sense amplifiers. PMID- 8354809 TI - Relation between left ventricular shape and exercise capacity in patients with left ventricular dysfunction. AB - OBJECTIVES: The aim of this study was to identify dynamic predictors of exercise duration in patients with systolic left ventricular dysfunction and to test the hypothesis that left ventricular shape is an independent determinant of exercise duration in these patients. BACKGROUND: Measurements of left ventricular volumes and ejection fraction at rest do not predict exercise capacity in patients with systolic left ventricular dysfunction. Left ventricular shape at rest has been reported to be an independent determinant of exercise duration in these patients. The significance of alterations in left ventricular shape that occur during dynamic exercise has not been investigated. METHODS: Twenty-one patients with a documented ejection fraction < 40% performed symptom-limited graded upright bicycle exercise with simultaneous quantitative two-dimensional echocardiography. End-diastolic volume, end-systolic volume, stroke volume, ejection fraction and sphericity index were measured at rest and peak exercise. RESULTS: Eleven patients exercised beyond stage II (6 min, 50 W), averaging 8.9 +/- 1.9 min; 10 patients were unable to complete stage II, averaging 4.9 +/- 0.9 min. No patient developed clinical evidence of ischemia during the exercise period. Of the echocardiographic variables considered, only end-systolic and end-diastolic sphericity indexes at peak exercise (r = 0.809 and 0.711, respectively) and the change in end-systolic sphericity index during exercise (r = 0.697) were strongly correlated with exercise duration. CONCLUSIONS: Conventional descriptors of left ventricular function are poor predictors of exercise capacity. Dynamic changes in heart shape correlate strongly with exercise duration and may be important determinants of exercise capacity in patients with systolic left ventricular dysfunction. PMID- 8354810 TI - Long-term follow-up (12 to 35 weeks) after dynamic cardiomyoplasty. AB - OBJECTIVES: To obtain information on the long-term effects of dynamic cardiomyoplasty on hemodynamics and muscle histology, this surgical method was evaluated in goats. BACKGROUND: Dynamic cardiomyoplasty has been introduced as a new method to treat patients with severe cardiac failure. METHODS: In 24 goats, the left latissimus dorsi muscle was wrapped around the heart. The muscle was then subjected to progressive electrical stimulation. In 16 goats, invasive transesophageal Doppler echocardiographic measurements and histologic evaluation of the latissimus dorsi muscle were performed at > or = 12 weeks after the wrapping. RESULTS: Only two goats showed an increase in aortic and left and right ventricular pressures concomitant with increased aortic flow during latissimus dorsi muscle stimulation both before and after induction of cardiac failure using imipramine. This was accompanied by a preserved latissimus dorsi muscle structure and nearly complete transformation to type I muscle fibers. The remaining 14 goats showed extensive lipomatosis in the latissimus dorsi muscle, with severe intimal hyperplasia and proliferation of smooth muscle cells in the walls of the thoracodorsal artery and its branches. An increase in endoneural and endomysial connective tissue was observed, with some goats showing destroyed nerve branches near the electrodes. These findings differed from those observed after long-term electrical stimulation of goat latissimus dorsi muscle in situ. CONCLUSIONS: Dynamic cardiomyoplasty is of use in the treatment of severe heart failure if the histologic structure of the wrapped latissimus dorsi muscle remains intact. Long term results in goats suggest that the current approach used in dynamic cardiomyoplasty may lead to deterioration of the wrapped muscle. PMID- 8354811 TI - Exercise-induced hypoxemia in heart transplant recipients. AB - OBJECTIVES: The purpose of this study was to determine whether heart transplantation has an adverse effect on pulmonary diffusion and to investigate the potentially deleterious effects of impaired pulmonary diffusion on arterial blood gas dynamics during exercise in heart transplant recipients. BACKGROUND: Abnormal pulmonary diffusing capacity is reported in patients after orthotopic heart transplantation. Abnormal diffusion may be caused by cyclosporine or by the persistence of preexisting conditions known to adversely affect diffusion, such as congestive heart failure and chronic obstructive pulmonary disease. METHODS: Eleven patients (mean age 50 +/- 14 years) performed pulmonary function tests 3 +/- 1 months before and 18 +/- 12 (mean +/- SD) months after heart transplantation. Transplant patients were assigned to groups with diffusion > 70% (n = 5) or diffusion < 70% of predicted values (n = 5). The control group and both subsets of patients performed 10 min of cycle exercise at 40% and 70% of peak power output. Arterial blood gases were drawn every 30 s during the 1st 5 min and at 6, 8 and 10 min. RESULTS: Significant improvements in forced vital capacity (17.4%), forced expiratory volume in 1 s (11.7%) and diffusion capacity (6.6%) occurred in the patients; however, posttransplantation vital capacity, forced expiratory volume and diffusion were lower (p < or = 0.05) compared with values in 11 matched control subjects. Changes in blood gases were similar among groups at 40% of peak power output. At 70% of peak power output, arterial blood gases and pH were significantly (p < or = 0.05) lower in transplant patients with low diffusion (arterial oxygen pressure 15 to 38 mm Hg below baseline) than in patients with normal diffusion and control subjects. Cardiac index did not differ (p > or = 0.05) between transplant patients with normal and low diffusion at rest or during exercise. Posttransplantation mean pulmonary artery pressure was significantly related to exercise-induced hypoxemia (r = 0.71; p = 0.03). CONCLUSIONS: Abnormal pulmonary diffusion observed in patients before heart transplantation persists after transplantation with or without restrictive or obstructive ventilatory defects. Heart transplant recipients experience exercise induced hypoxemia when diffusion at rest is < 70% of predicted. Our data also suggest that abnormal pulmonary gas exchange possibly contributes to diminished peak oxygen consumption in some heart transplant recipients; however, direct testing of this hypothesis was beyond the scope of the present study. This possibility needs to be investigated further. PMID- 8354812 TI - Effect of exercise on valvular resistance in patients with mitral stenosis. AB - OBJECTIVES: This exercise study assessed the relation between valvular resistance and flow in patients with mitral stenosis. BACKGROUND: Valvular resistance has been proposed as an alternative measure of stenotic valvular lesions, which is speculated to remain stable under changing hemodynamic conditions. METHODS: In 35 of 40 patients with pure or predominant mitral stenosis, continuous wave Doppler measurements of the mitral stenotic jet were possible at rest and during supine bicycle ergometry. Simultaneously, transvalvular flow was assessed by thermodilution technique. For calculation of valvular resistance, the mean mitral valve pressure gradient was determined according to the simplified Bernoulli equation and divided by transvalvular flow. Additionally, effective mitral valve area was calculated according to the continuity equation method, dividing flow by the mean diastolic flow velocity. RESULTS: Valvular resistance was 65 +/- 32 dynes.s.cm-5 at rest and increased to 82 +/- 43 dynes.s.cm-5 at 25 W (p < 0.001). The most prominent increase in valvular resistance (rest to 25 W 63 +/- 28 to 95 +/- 48 dynes.s.cm-5, p < 0.001) was found in those patients who had no or only a moderate (< 20%) change in effective mitral valve area. In contrast, valvular resistance remained constant (67 +/- 36 vs. 70 +/- 32 dynes.s.cm-5) in patients with a significant (> or = 20%) increase in mitral valve area with exercise. CONCLUSIONS: In patients with mitral stenosis, the exercise-induced changes in valvular resistance are heterogeneous. This is the result of the variable response of mitral valve area to an increase in flow. In the individual patient, mitral valve area can significantly increase, a factor that has to be taken into account when interpreting the hemodynamic relevance of the obstruction. Calculated valvular resistance is flow dependent and has no advantage over valve area calculations for quantifying mitral stenosis. PMID- 8354813 TI - Mechanisms and outcome of severe mitral regurgitation after Inoue balloon valvuloplasty. North American Inoue Balloon Investigators. AB - OBJECTIVES: The purpose of this study was to assess the incidence, mechanism and outcome of severe mitral regurgitation after treatment of mitral stenosis with percutaneous mitral valvuloplasty using the Inoue balloon. BACKGROUND: Severe mitral regurgitation occurs in up to 15% of percutaneous balloon valvuloplasty procedures for acquired mitral stenosis. The incidence and mechanism of production of mitral regurgitation with the recently introduced single-balloon Inoue technique have not been characterized. METHODS: We examined the incidence, mechanism, predictors and outcome of severe mitral regurgitation after Inoue balloon valvuloplasty in 280 patients in the North American multicenter registry. Twenty-one patients who developed either clinically significant or angiographically severe regurgitation were identified, and their echocardiograms were reviewed to determine the mechanism of regurgitation. These patients were then compared with the remaining patients without severe regurgitation to identify predictors of this outcome. RESULTS: The incidence of severe regurgitation in this study was 7.5%, and the mean grade of angiographic regurgitation in these patients increased from 0.9 +/- 1.0 to 2.8 +/- 0.7 (p < 0.05). The most common cause of regurgitation (43%) was rupture of chordae tendineae to the anterior or posterior mitral leaflet. Tearing of a leaflet (usually the posterior one) occurred in 30% of patients; and no recognizable structural abnormality, with wide splitting of the commissures and a central regurgitant jet, was present in five patients (26%). All patients with definite posterior leaflet tears had heavily calcified leaflets. Patients who developed severe regurgitation had fewer balloon inflations and a higher grade of preexisting mitral regurgitation but were otherwise similar to the remaining patients without severe regurgitation. During 6-month follow-up, 71% of the patients with severe regurgitation were treated surgically; the grade of regurgitation decreased in four patients (19%), and five patients (24%) have not required mitral valve replacement during 18 +/- 5 months of follow-up. CONCLUSIONS: Severe mitral regurgitation is a relatively infrequent complication of Inoue balloon valvuloplasty and results from disruption of the valve integrity, including chordal rupture and leaflet tearing. Careful balloon positioning may help avoid chordal rupture, and heavily calcified posterior leaflets may be at greater risk of tearing. Most patients who develop severe regurgitation will require nonemergency mitral valve replacement. PMID- 8354814 TI - Role of left ventricular regional nonuniformity in hypertensive diastolic dysfunction. AB - OBJECTIVES: This study investigated 1) the role of left ventricular diastolic nonuniformity in hypertensive left ventricular diastolic dysfunction, and 2) the effects of a calcium channel antagonist on diastolic nonuniformity in hypertensive and normotensive subjects. BACKGROUND: Augmented left ventricular diastolic nonuniformity contributes to diastolic dysfunction in hypertrophic cardiomyopathy. Impaired left ventricular diastolic function with preserved systolic function has been recognized in hypertension. Therefore, abnormal ventricular regional nonuniformity might also be involved in hypertensive diastolic dysfunction in a milder form of hypertrophy. METHODS: Thirteen patients with established hypertension underwent radionuclide ventriculography before and after nifedipine administration. Indexes of left ventricular function were derived by computer analysis of the time-activity curve. After a computer subdivided the left ventricle into four regions, a time-activity curve of each region was constructed to determine an index of left ventricular diastolic nonuniformity. This index was calculated as the sum of the absolute values of time difference between global and regional peak filling in the septal, the apical and the lateral region. Ten normotensive subjects were studied for comparison. Echocardiography was performed in both groups. RESULTS: The two groups were matched for age, gender, heart rate, echocardiographic dimensions and systolic function. In the hypertensive group, left ventricular diastolic filling indexes were impaired, with a negative correlation between peak filling rate and the diastolic nonuniformity index. Although the change in ejection fraction after nifedipine administration was similar in the two groups, the increase in peak filling rate was larger in the hypertensive patients. The diastolic nonuniformity index decreased after nifedipine in the hypertensive but not in the control group. This decrease correlated with improved peak filling rate in the hypertensive group. CONCLUSIONS: In hypertensive patients with preserved systolic function, left ventricular diastolic nonuniformity increases, causing early diastolic dysfunction. Decreased diastolic nonuniformity after pharmacologic intervention contributes to lessened ventricular filling dysfunction, regardless of changes in loading conditions in hypertension. Thus, diastolic nonuniformity is an important determinant of left ventricular filling abnormality and might be a target of pharmacologic intervention in hypertensive patients. PMID- 8354815 TI - Hypertrophic cardiomyopathy in the young: another form of ischemic cardiomyopathy? PMID- 8354816 TI - Restrictive left ventricular filling pattern in dilated cardiomyopathy assessed by Doppler echocardiography: clinical, echocardiographic and hemodynamic correlations and prognostic implications. Heart Muscle Disease Study Group. AB - OBJECTIVES: This study was undertaken to evaluate the frequency of restrictive left ventricular filling pattern in dilated cardiomyopathy, as well as its clinical and hemodynamic correlations and prognostic implications. BACKGROUND: In dilated cardiomyopathy, as in other heart diseases, different left ventricular filling patterns were observed on Doppler echocardiography. Some patients showed a "restrictive filling pattern," similar to that associated with restrictive cardiomyopathy, characterized by predominant E waves and a shortened E deceleration time. METHODS: Pulsed Doppler transmitral curves were analyzed in 79 consecutive patients with dilated cardiomyopathy assigned to two study groups according to E deceleration time: group 1 (n = 36) had a restrictive left ventricular filling pattern (E deceleration time < 115 ms); group 2 (n = 43) had an E deceleration time > or = 115 ms. RESULTS: Patients in group 1 were significantly younger, in a higher New York Heart Association functional class, more frequently had a third heart sound and had a higher left ventricular filling pressure at catheterization. In addition, they showed more severe left and right ventricular dysfunction and dilation, a larger left atrium and more severe mitral regurgitation. A restrictive filling pattern was associated at Doppler study with a higher E wave velocity, lower A wave velocity and higher E/A ratio. During a follow-up interval of 22 +/- 14 months, all 14 patients who subsequently died or required heart transplantation showed a restrictive left ventricular filling pattern. At multivariate analysis, E deceleration time was the most powerful independent prognostic indicator of poor outcome or transplantation. CONCLUSIONS: Restrictive left ventricular filling pattern is frequent in dilated cardiomyopathy, is associated with more severe disease and is a powerful indicator of increased mortality risk and need for heart transplantation. PMID- 8354817 TI - An echocardiographic study of the fluid mechanics of obstruction in hypertrophic cardiomyopathy. AB - OBJECTIVES: The goal of this study was to investigate the hydrodynamic cause of mitral-septal contact and obstruction in patients with hypertrophic cardiomyopathy. BACKGROUND: Mitral-septal apposition has been shown to be the cause of obstruction in patients with hypertrophic cardiomyopathy. With obstruction, characteristic continuous wave Doppler tracings show an increasing acceleration of flow. (Tracing is concave to the left.) METHODS: We studied 24 consecutive patients who had a Doppler echocardiographic pressure gradient > or = 36 mm Hg. We pursued two lines of inquiry. 1) Before the onset of obstruction, we systematically measured the angle between the direction of left ventricular Doppler color flow and the protruding mitral leaflet in early systole. 2) After the onset of obstruction, we qualitatively analyzed the concave contour of the continuous wave Doppler tracings in our patients and developed a hydrodynamic theory of the obstruction phase to explain the characteristic tracings. We present a mathematic model to support this concept. RESULTS: We measured 129 angles. Just before mitral-septal contact, the protruding mitral leaflet projects at a mean 40 degrees and 45 degrees relative to flow in the apical long-axis and apical five-chamber views, respectively. At mitral-septal contact, the obstructing leaflet projects at a mean 52 degrees and 58 degrees relative to flow in the same respective views. Even very early in systole, at leaflet coaptation, 11 of 23 patients had angles > 15 degrees relative to flow. After mitral-septal apposition, obstruction across a cowl-shaped orifice begins. During this stage, the obstructing leaflet projects at a mean 55 degrees and 63 degrees relative to flow. In 22 patients, the continuous wave Doppler tracing of the left ventricular outflow jet showed an increasing acceleration of flow. CONCLUSIONS: Just before mitral-septal contact, the protruding leaflets project at high angles relative to flow. At these high angles, flow drag, the pushing force of flow, is the dominant hydrodynamic force on the protruding leaflet and appears to be the immediate cause of obstruction. The high angle between flow direction and the protruding leaflet precludes significant Venturi effects. Even earlier in systole, at leaflet coaptation, flow drag is dominant in half of the patients, with angles relative to flow > 15 degrees. After obstruction is triggered, it appears from our data and model that the leaflet is forced against the septum by the pressure difference across the orifice. The increasing acceleration of Doppler flow is explained by a time-dependent amplifying feedback loop in which the rising pressure difference across the orifice leads to a smaller orifice and a higher pressure difference. PMID- 8354819 TI - Congestive heart failure in rheumatic carditis: valvular or myocardial origin? PMID- 8354818 TI - Evidence against a myocardial factor as the cause of left ventricular dilation in active rheumatic carditis. AB - OBJECTIVES: The aim of this study was to determine whether left ventricular dilation and congestive heart failure in patients with acute rheumatic fever with carditis are accompanied by left ventricular contractile dysfunction. BACKGROUND: Acute rheumatic fever with carditis involves both the myocardium and endocardium, with consequent valvular regurgitation. The relative contribution of volume overload induced by valvular regurgitation and myocardial dysfunction due to rheumatic myocarditis to the overall degree of left ventricular dilation and congestive heart failure in these patients is unknown. METHODS: To investigate this, we evaluated 32 patients (15 male, 17 female, mean age 14 +/- 3 years) with documented active carditis and congestive heart failure. All 32 patients were found to have significant isolated mitral regurgitation or combined mitral and aortic regurgitation. Echocardiographic analysis of left ventricular dimensions and systolic performance was performed before and after isolated mitral or combined mitral and aortic valve replacement and the results were compared with those in 19 control subjects matched for age, gender and body surface area. RESULTS: Both preoperative left ventricular end-diastolic diameter and percent fractional shortening were significantly increased in patients compared with control subjects (57 +/- 7 vs. 43 +/- 3 mm, p < 0.001, and 38 +/- 6% vs. 33 +/- 1%, p < 0.001, respectively). After valve replacement, left ventricular end diastolic diameter decreased significantly (57 +/- 7 to 47 +/- 6 mm, p < 0.001). Although percent fractional shortening decreased significantly postoperatively (38 +/- 6% to 32 +/- 6%, p < 0.001), the postoperative percent fractional shortening did not differ from that in control subjects (32 +/- 6% vs. 33 +/- 1%, p = NS). CONCLUSIONS: The results of this study indicate that left ventricular dilation and heart failure in patients with acute rheumatic carditis rarely occur in the absence of hemodynamically significant regurgitant valve lesions. Furthermore, rapid reduction in left ventricular dimensions and preservation of fractional shortening after isolated mitral or combined mitral and aortic valve replacement suggest that rheumatic carditis is not accompanied by any significant degree of myocardial contractile dysfunction. PMID- 8354820 TI - Accurate preoperative diagnosis of pericardial constriction using cine computed tomography. AB - OBJECTIVES: The purpose of this study was to determine the accuracy of cine computed tomography in the diagnosis of constrictive pericarditis. BACKGROUND: Constrictive pericarditis is characterized by abnormalities of both cardiac structure and function. Accurate diagnosis requires detection of both a thickened pericardium and abnormal ventricular diastolic filling. At present, no one diagnostic technique has demonstrated sufficient accuracy in this setting. Cine computed tomography is a relatively new cardiac imaging mode with very high time and spatial resolution that has the potential to accurately diagnose constrictive pericarditis. METHODS: Twelve consecutive patients were retrospectively identified who had catheterization findings suggestive of constrictive physiology, had undergone a cine computed tomographic examination and had pathologic data that delineated the status of the pericardium. Group 1 (with constrictive pericarditis; n = 5) had surgical confirmation of thickened pericardium and improved clinically after pericardiectomy. Group 2 (no constrictive pericarditis; n = 7) had cardiomyopathy with normal pericardium. Seven normal volunteers (Group 3) were also studied. Cine computed tomograms were obtained for the entire heart (8-mm slices, 17 frames/s, nonionic contrast medium). Pericardial thickness was measured at 10 degrees intervals at three ventricular levels in each subject. The rapidity of diastolic filling was assessed by calculating the percent filling fraction in early diastole. RESULTS: Pericardial thickness was 10 +/- 2 mm (mean +/- SD) in Group 1, 2 +/- 1 mm in Group 2 and 1 +/- 1 mm in Group 3 (p < 0.05, constrictive pericarditis vs. no constrictive pericarditis). Left ventricular filling fraction was 83 +/- 6% in Group 1, 62 +/- 9% in Group 2 and 44 +/- 5% in Group 3. Right ventricular filling fraction was 93 +/- 5% in Group 1, 62 +/- 14% in Group 2 and 35 +/- 6% in Group 3 (p < 0.05, Group 1 vs. Groups 2 and 3). Both indexes provided a clear-cut distinction between patients with and without constriction. CONCLUSIONS: Cine computed tomography simultaneously provides both anatomic and physiologic data that allow accurate preoperative diagnosis of pericardial constriction. PMID- 8354821 TI - Ultrasonic backscatter system for automated on-line endocardial boundary detection: evaluation by ultrafast computed tomography. AB - OBJECTIVES: The purpose of this study was to evaluate the accuracy of the recently developed echocardiographic on-line endocardial border detection system using ultrafast computed tomography, an independent and proved tomographic imaging modality. BACKGROUND: The automated system for on-line endocardial border detection identifies the blood-tissue interface by acoustic quantification of the ultrasonic backscatter signal. METHODS: Eighteen subjects were screened by conventional echocardiography and acoustic quantification. Ten of these, with high quality echocardiographic images, were also examined by ultrafast computed tomography. Comparable image planes at the midpapillary level were analyzed. Measurements of left ventricular cavity area were compared at end-diastole and end-systole and time course analyses of cavity area during the cardiac cycle were performed. RESULTS: There was good correlation between values for left ventricular end-diastolic area (r = 0.99), end-systolic area (r = 0.93) and fractional area change (r = 0.91) using the two methods. The on-line backscatter system underestimated end-diastolic area (p < 0.001), but the negative bias was small (-1.6 cm2) and the 95% confidence intervals were narrow (-3.6 cm2 to +0.4 cm2). In contrast, the backscatter system overestimated end-systolic area (p < 0.02); the positive bias for this variable was also small (+2.6 cm2) but the confidence intervals were relatively wide (+7.9 to -2.8 cm2). The negative bias of backscatter values for cavity area was fairly constant during diastole and early systole (range -5% to -10%), but during the second half of systole, backscatter values increased progressively relative to computed tomographic values. Real time values for fractional area change measured by the backscatter system were 13% smaller than those determined by ultrafast computed tomography (p < 0.001), with wide confidence intervals (+3% to -30%). Absolute peak rates of area change during systole and diastole were lower by 39% (p < 0.001) and 41% (p < 0.01), respectively, using the on-line ultrasonic backscatter system. Time course analyses revealed the errors to be consistent with cardiac cycle-dependent alterations in gain sensitivity of the ultrasonic backscatter system. CONCLUSIONS: The ultrasonic backscatter system is associated with cyclic cavity area measurement errors that need to be addressed if its early promise for on line assessment of ventricular function is to be fulfilled. Incorporation of an electrocardiographically triggered time-varying gain control may improve accuracy for on-line analysis of ventricular performance. PMID- 8354822 TI - The search for intelligent quantitation in echocardiography: "eyeball," "trackball" and beyond. PMID- 8354823 TI - Predictive factors for spontaneous closure of atrial septal defects diagnosed in the first 3 months of life. AB - OBJECTIVES: To establish the rate of spontaneous closure of atrial septal defects diagnosed before age 3 months, 101 infants (mean age 26 days) with an interatrial shunt confirmed by Doppler echocardiography were followed up for an average of 265 +/- 190 days. BACKGROUND: Even if interatrial shunts in the newborn are frequently encountered, little is known about their natural history. METHODS: Defect diameter on two-dimensional echocardiography and width of color flow jet were measured in the subcostal view. Right and left ventricular diameters and atrial septal curvature were also studied. Kaplan-Meier curves were obtained to predict age of spontaneous closure in relation to initial defect diameter. RESULTS: There was no significant correlation between the diameter of the atrial septal defect and right ventricular/left ventricular ratio or type of septal curvature (vertical or concave toward the left atrium). The classic predominance of girls over boys was observed only for defects > 5 mm. An overall rate of spontaneous closure of 87% was observed. Frequency and timing of closure were inversely correlated to atrial septal defect diameter: closure occurred in 100% (32 of 32) of defects in group 1 (diameter < 3 mm), 87% of defects (39 of 45) in group 2 (diameter 3 to 5 mm), 80% of defects (16 of 20) in group 3 (diameter 5 to 8 mm). Spontaneous closure did not occur in four patients of group 4 (defect > or = 8 mm) during an average follow-up interval of 417 days (range 294 to 597 days). CONCLUSIONS: These results suggest that infants with an atrial septal defect < 3 mm need not be followed up as 100% of these defects will be closed by age 18 months; those with a defect 3 to 5 or 5 to 8 mm should be evaluated by the end of the 12th and the 15th month, respectively, when > 80% of these defects will be closed. An atrial septal defect with a diameter > or = 8 mm may have little chance of closing spontaneously and the possibility of surgical correction should be considered. Defects < 3 mm probably do not constitute a cardiac malformation in light of their natural evolution and gender distribution. PMID- 8354824 TI - Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents. AB - OBJECTIVES: Because endothelial dysfunction is an early event in atherogenesis, we aimed to determine whether endothelial function is normal or impaired in the systemic arteries of children with homozygous homocystinuria or in those of heterozygous adults, or both. BACKGROUND: Homocystinuria is strongly associated with premature vascular disease in homozygotes, and even heterozygotes have been shown to be at increased risk from early atherosclerosis associated with hyperhomocystinemia. METHODS: We conducted noninvasive studies on the superficial femoral or brachial arteries of 9 children aged 4 to 17 years (mean 11) with homozygous homocystinuria and on the brachial arteries of 14 obligate heterozygous parents age 33 to 49 years (mean 41). Each subject was matched with two control subjects. Using high resolution ultrasound, we measured vessel diameter at rest, during reactive hyperemia (with flow increase causing endothelium-dependent dilation) and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator). RESULTS: Flow-mediated dilation was observed in the control children (9 +/- 0.6%, range 6% to 14%) but was impaired in the children with homocystinuria (2.8 +/- 0.7%, range 0% to 7%, p < 0.0001). In contrast, nitroglycerin-mediated dilation was similar in both groups (15.7 +/- 1.6% vs. 13.1 +/- 1.2%, p = 0.27), indicating that the impaired flow-mediated dilation is secondary to endothelial dysfunction. In the heterozygous parents, both flow-mediated dilation and nitroglycerin responses (6.3 +/- 0.9%, 17 +/- 1.4%, respectively) were similar to control values (6.8 +/- 0.7%, 20.7 +/- 1.7%, p > 0.10). CONCLUSIONS: Children with homozygous homocystinuria had impaired endothelial function in the systemic arteries as early as 4 years of age, representing an early event in their premature vascular disease. However, endothelial function was preserved in the heterozygous adults. PMID- 8354825 TI - Balloon angioplasty for postoperative pulmonary artery stenosis in transposition of the great arteries. AB - OBJECTIVES: This study was designed to assess the success rate and determinants of success or failure of balloon angioplasty for postoperative pulmonary stenosis in patients with transposition of the great arteries. BACKGROUND: Previous reports have suggested that pulmonary stenosis that develops after the arterial switch operation is not likely to be dilated. METHODS: Twenty-eight patients with transposition of the great arteries underwent 39 balloon angioplasty procedures after the arterial switch operation. The mean age at dilation was 4.5 +/- 2.2 years (range 0.7 to 9.8), and the interval between operation and balloon dilation was 3.6 +/- 1.8 years. The criterion of successful dilation was a > or = 50% increase in predilation diameter or a > or = 50% decrease in predilation pressure gradient. If the right ventricular/aortic pressure ratio decreased by > or = 0.2, so that the ratio became < 0.68, reoperation was thought to be not indicated. RESULTS: The success rate of balloon angioplasty for pulmonary artery stenosis was 51% (20 of 39 dilations). The mean age at dilation in the group with successful dilation (3.6 years) was significantly younger than that in the group with unsuccessful dilation (5.4 years). The interval between operation and dilation in the successful dilation group (2.4 years) was significantly less than that in the unsuccessful dilation group (4.6 years). In 13 patients who underwent balloon angioplasty < 3.5 years after operation, balloon dilation was successful in 92%. The balloon/artery ratio was significantly greater in the successful than in the unsuccessful dilation group. A right ventricular/aortic pressure ratio > or = 0.68 was observed in 20 patients, and reoperation was not indicated in 10 patients (50%). There was no death, but one pulmonary artery rupture that did not require surgical intervention occurred. Aneurysmal dilation of the pulmonary artery was observed in three patients. CONCLUSIONS: These data indicate that although the success rate of balloon angioplasty for pulmonary artery stenosis after the arterial switch operation is low (approximately 50%), balloon angioplasty can be the first therapeutic choice owing to the low complication rate and the potential benefit of the procedure. The success rate can be high if angioplasty is performed < 3.5 years after operation and a balloon of adequate size is used. PMID- 8354826 TI - High pressure balloon angioplasty for branch pulmonary artery stenosis: early experience. AB - OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of high pressure balloons (17 to 20 atm, Blue Max, Meditech) to dilate branch pulmonary artery stenosis. BACKGROUND: The low success rate (50% to 60%) for angioplasty of branch pulmonary artery stenosis using low pressure balloons is due primarily to the inability to eliminate the balloon waist. Hence, higher inflation pressures may improve results. METHODS: Hemodynamic and angiographic data from 52 patients (0.3 to 34.8 years old) who underwent high pressure balloon dilation of branch pulmonary artery stenosis between October 1990 and February 1992 were reviewed retrospectively, as were data from previous low pressure dilations in these patients. Common diagnoses included tetralogy of Fallot (n = 9), tetralogy of Fallot with pulmonary atresia (n = 23), single ventricle (n = 8) and isolated congenital pulmonary stenosis (n = 7). The 52 patients had 72 vessels dilated. Criteria for success were a > or = 50% increase in vessel diameter or a > 20% decrease in right ventricular to aortic pressure ratio. RESULTS: Of 36 vessels with previously unsuccessful low pressure balloon dilation, 23 (63%) were successfully dilated with high pressure balloons. Of the 36 remaining vessels, 29 (81%) were successfully dilated with high pressure balloons. Factors associated with success were stenosis at a surgical anastomosis and disappearance of the balloon waist with dilation. Aneurysms developed in three vessels. Complications occurred in seven patients (13%); in two patients the distal pulmonary artery was perforated by a stiff guide wire, causing death in one. CONCLUSIONS: Dilation of stenotic peripheral pulmonary arteries with high pressure balloons improves the success rate of angioplasty both in patients who have had unsuccessful dilation with a low pressure balloon and in those without previous attempted dilation. PMID- 8354827 TI - Scimitar syndrome in infancy. AB - OBJECTIVES: The objectives of this study were to determine the anatomic and physiological factors most responsible for the severe symptoms and poor prognosis of infants with scimitar syndrome. BACKGROUND: Whereas the diagnosis of scimitar syndrome is often made incidentally in older children and adults who undergo chest radiography for diverse reasons, infants in whom the diagnosis is made typically present with severe symptoms and have a poor prognosis. METHODS: The clinical, catheterization and imaging data of 13 consecutive infants with scimitar syndrome who underwent cardiac catheterization in the 1st 6 months of life were reviewed, with emphasis on the pulmonary artery pressure, pulmonary and cardiovascular anatomy, therapeutic interventions and outcome. RESULTS: Twelve of the 13 infants had pulmonary hypertension at the time of diagnosis. Six patients died despite specific treatment. Eleven of 13 infants had associated cardiac malformations and 9 had large systemic arterial collateral channels to the right lung. Seven patients had anomalies involving the left side of the heart, especially varying degrees of hypoplasia of the left heart or aorta, and six of these patients died. Ten patients underwent surgical or transcatheter therapy in the 1st year of life. Systemic arteries to the right lung were ligated in three patients and occluded by transcatheter embolization in four. Balloon angioplasty was carried out in two patients, one with stenosis of the left-sided pulmonary veins and one with stenosis of the anomalous right pulmonary vein. The latter had placement of a balloon-expandable stent. In both patients, pulmonary vein stenosis progressed. Six patients had surgical repair of associated cardiovascular anomalies, and two required repair of extracardiac congenital anomalies. Occlusion of the anomalous systemic arteries was generally associated with clinical improvement, but congestive heart failure and pulmonary hypertension recurred in those patients with associated cardiovascular anomalies, whose condition subsequently responded after correction of the shunt lesions. CONCLUSIONS: The severe symptoms and pulmonary hypertension found in infants with scimitar syndrome have many causes. Anomalous systemic arterial supply, pulmonary vein stenosis and associated cardiovascular anomalies play a significant role, and the ultimate outcome of individual infants depends on the feasibility of treating these anomalies in early infancy. PMID- 8354828 TI - Radiofrequency catheter ablation of supraventricular arrhythmias in patients with congenital heart disease: results and technical considerations. AB - OBJECTIVES: The aim of this study was to report the results and techniques of radiofrequency ablation for treatment of supraventricular arrhythmias in patients with congenital structural heart disease. BACKGROUND: The management of patients with congenital and other structural heart disease may be complicated by serious arrhythmias due to Wolff-Parkinson-White syndrome or by atrial arrhythmias after cardiac surgery. Ablation techniques using radiofrequency current are revolutionizing the management of arrhythmias, but reports have included few with structural heart disease. METHODS: Fifteen patients with significant heart disease underwent radiofrequency ablation: 11 with Wolff-Parkinson-White syndrome and 4 with intraatrial reentrant tachycardia after atrial surgery. Seven had Ebstein's anomaly, complex in two, and the rest had other defects. Coexistence of structural defects introduced significant technical difficulties to radiofrequency ablation in patients with the Wolff-Parkinson-White syndrome and was accomplished by adaptation of current techniques. Ablation of intraatrial reentrant tachycardia was performed by finding early atrial activation sites with electrogram fractionation for radio-frequency application. RESULTS: Radiofrequency ablation was initially successful in 14 of 15 patients, with cure in 10 and clinical improvement in 14. Two patients subsequently underwent cardiac surgery without perioperative arrhythmias. CONCLUSIONS: Radiofrequency ablation in patients with congenital heart disease and arrhythmias in both safe and effective and may be the preferred approach to treatment in some patients. In patients who are to undergo surgical correction or palliation, preoperative radiofrequency ablation of the tachycardia substrate is effective and may be preferred to operative accessory pathway division. The ablation of intraatrial reentrant tachycardia shows promise in the management of patients who have undergone extensive atrial surgery, and it may eventually become the preferred approach, particularly when there are contraindications to the use of antiarrhythmic agents. PMID- 8354829 TI - Dual natriuretic peptide system in experimental heart failure. AB - OBJECTIVES: The objectives of this study were 1) to define in an experimental model of heart failure the time course of changes in plasma brain natriuretic peptide concentrations during the development of and recovery from heart failure, and 2) to relate the changes to changes in atrial natriuretic peptide concentration and hemodynamic status. BACKGROUND: Brain natriuretic peptide is a circulating peptide with homology to atrial natriuretic peptide. However, unlike the latter, its changes during heart failure and its relation to cardiac filling pressures have not been studied. METHODS: Eight male mongrel dogs underwent right ventricular pacing at 250 beats/min for 3 weeks until heart failure occurred and were followed up during recovery for 4 weeks after cessation of pacing. RESULTS: Heart failure was characterized by an increase in both left ventricular and end diastolic pressure (6.6 +/- 4.1 mm Hg at the control measurements to 35.1 +/- 5.9 mm Hg at 3 weeks, p < 0.01) and right atrial pressure (6.7 +/- 1.1 to 11.4 +/- 2.1 mm Hg, p < 0.01). Recovery was accompanied by a return of cardiac filling pressures to control level. The time course of change of arterial plasma brain natriuretic peptide concentration was similar to that of atrial natriuretic peptide. Plasma concentrations of both peptides increased after 1 week of pacing (16 +/- 4 pg/ml at the control measurement to 59 +/- 20 pg/ml at 1 week, p < 0.001 for brain natriuretic peptide and 84 +/- 55 to 856 +/- 295 pg/ml, p < 0.001 for atrial natriuretic peptide). The level of both peptides then stayed level with no further increase at 3 weeks and returned to the control value by 4 weeks of recovery. There was an excellent correlation between plasma concentrations of the two peptides (r = 0.86, p < 0.001) and between the two peptides and cardiac filling pressures. However, compared with atrial natriuretic peptide, plasma brain natriuretic peptide concentration had a smaller percent increase during evolving heart failure and a slower rate of decline at recovery. CONCLUSIONS: Brain and atrial natriuretic peptide constitute a dual natriuretic system and are both responsive to changes in cardiac filling pressures in heart failure. However, brain natriuretic peptide appears to be less responsive than atrial natriuretic peptide. PMID- 8354830 TI - Graded myocardial ischemia is associated with a decrease in diastolic distensibility of the remote nonischemic myocardium in the anesthetized dog. AB - OBJECTIVES: This study was designed to investigate the changes in regional distensibility of the ischemic segment and of a remote nonischemic segment brought about by graded myocardial ischemia. BACKGROUND: Ventricular distensibility is a major determinant of left ventricular end-diastolic pressure. The effects of graded myocardial ischemia on the regional distensibility of the ischemic area have not been studied. Moreover, there are few data on the effects of myocardial ischemia on the regional distensibility of the nonischemic myocardium. METHODS: Nine anesthetized open chest mongrel dogs were fitted with instruments to measure left ventricular pressure and circumferential length (sonomicrometry) in the ischemic segment and in a nonischemic segment. The pressure-length relation was modified by stepwise infusion and withdrawal of 200 ml of each dog's own blood over 30 min in five consecutive stages of regional ischemia. Unstressed dimensions were obtained by repeated inferior vena cava occlusions. In both segments, regional distensibility was assessed at end diastole by means of the constants of the pressure-length (chamber stiffness), the pressure-strain and the force-strain (myocardial stiffness) relations. RESULTS: In the ischemic segment, partial and complete coronary occlusions were associated with a twofold increase in the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant, whereas in the nonischemic segment the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant increased by 50%. CONCLUSIONS: Regional myocardial ischemia is associated with a decrease in distensibility of both the ischemic and the remote nonischemic myocardium. PMID- 8354831 TI - Left ventricular diastolic collapse in regional left heart cardiac tamponade. An experimental echocardiographic and hemodynamic study. AB - OBJECTIVES: This study was designed to describe the hemodynamic abnormalities associated with the appearance of left ventricular diastolic collapse in the setting of regional left heart cardiac tamponade. BACKGROUND: Cardiac tamponade after heart surgery is frequently associated with localized pericardial effusion. Although right ventricular diastolic collapse and right atrial collapse are reliable echocardiographic findings in patients with circumferential pericardial effusion and tamponade, they are often not present in postoperative patients with localized pericardial effusion and regional left heart tamponade. Left ventricular diastolic collapse has been described in such patients, but the degree of hemodynamic alteration that exists with this finding is not known. METHODS: Acute regional left heart tamponade was produced 14 times in seven spontaneously breathing anesthetized dogs by infusing fluid into an isolated compartment created in the pericardial space adjacent to the left ventricular free wall. Continuous echocardiographic imaging and hemodynamic monitoring of left ventricular, systemic arterial, right atrial, pulmonary capillary wedge and pericardial pressures were performed. Measurements at baseline were compared with those made at the onset of left ventricular diastolic collapse and at decompensated tamponade. RESULTS: Left ventricular diastolic collapse was noted in all 14 episodes of regional tamponade. It occurred when pressure in the left pericardial compartment exceeded left ventricular diastolic pressure by 3.0 +/- 1.9 mm Hg. At the onset of left ventricular diastolic collapse, cardiac output and mean arterial pressure were significantly reduced from the control value (p < 0.05). Systolic hypotension was noted only twice at this stage, respiratory variation in systolic pressure > 10 mm Hg only once. The appearance of this sign was also associated with elevated left heart filling pressures. CONCLUSIONS: Left ventricular diastolic collapse is a reliable sign of regional left ventricular tamponade and is associated with a reduction in cardiac output. This echocardiographic finding usually occurs before the development of arterial hypotension and pulsus paradoxus. Thus, left ventricular diastolic collapse is potentially more reliable than hypotension or pulsus paradoxus in the diagnosis of regional left ventricular tamponade. PMID- 8354832 TI - Influence of heparin and systemic lysis on coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary thrombosis. AB - OBJECTIVES: We sought to evaluate whether anticoagulation by an intravenous heparin infusion prevents deterioration of coronary blood flow restored by the novel recombinant plasminogen activator BM 06.022, and to compare the effects of profound fibrinogenolysis with those of an intravenous bolus injection of heparin. BACKGROUND: Recent clinical studies indicate that heparin appears to be effective in reducing reocclusion when combined with recombinant tissue-type plasminogen activator (rt-PA), but that heparin is associated with an increased bleeding incidence. Therefore, the need for heparin has to be critically evaluated in the development of BM 06.022. METHODS: BM 06.022 is an unglycosylated variant of human tissue-type plasminogen activator. Thrombus formation in anesthetized open chest dogs was induced by electrical injury. Left circumflex coronary artery blood flow was monitored for 4 h using an electromagnetic flow probe. Twenty dogs were randomized to receive intravenous heparin (100 IU/kg bolus plus 100 IU/kg per h) in group B or saline solution in group A before an intravenous bolus injection of 200 kU/kg (= 0.34 mg/kg) BM 06.022 1 h after thrombus formation. Another 14 dogs were randomized to receive a single intravenous bolus injection of 200 IU/kg heparin plus 200 kU/kg BM 06.022 in group D or saline solution plus 1,000 kU/kg BM 06.022 in group C. RESULTS: In the absence of a systemic lytic state, heparin infusion prolonged (p < 0.05) the cumulative patency time (sum of time intervals during which the coronary artery was patent) to 204.3 +/- 7.4 min (group B) compared with 34.6 +/- 10.8 min with saline solution (group A), and increased (p < 0.05) the area under the curve for coronary blood flow versus time (AUCFlow) to 34.0 +/- 3.4 ml.h.min-1 compared with 7.7 +/- 4.6 ml.h.min-1. Profound fibrinogenolysis after administration of 1,000 kU/kg BM 06.022 (group C) and a single intravenous heparin injection (group D) did not differ in their effects on the cumulative patency time (182 +/- 30.3 vs. 177.5 +/- 25.4 min) and AUCFlow (36.0 +/- 10.3 vs. 30.5 +/- 4.8 ml.h.min-1), but these values were improved (p < 0.05) compared with those obtained after administration of saline solution plus 200 kU/kg BM 06.022 (group A). CONCLUSIONS: In the absence of a systemic lytic state, intravenous heparin is required as an adjunct to BM 06.022 to maintain coronary blood flow in dogs. PMID- 8354833 TI - Physics and engineering of transcatheter cardiac tissue ablation. AB - Ablation of arrhythmogenic cardiac tissues has emerged as one of the most important advances in cardiac electrophysiology. With the introduction of transcatheter ablation, the treatment of ventricular tachycardia, Wolff-Parkinson White syndrome and other cardiac arrhythmias has progressed from an expensive and painful surgical therapy accompanied by a long recovery period to the less expensive, less traumatic transcatheter approach. The feasibility of cardiac ablation, along with the increasing number of physicians using the technique, requires understanding of the anatomic and electrophysiologic bases of transcatheter ablation as well as the different technologies, their limitations and complications. This report provides an overview of the physical, scientific and technical aspects of cardiac ablation performed with the methods currently available and a summary of the limitations of each method and expected future technologic developments in this growing field. Emphasis is placed on radiofrequency and direct current energies, the primary methods now used. Methods such as cryoablation and laser, and microwave and chemical ablation are discussed with less detail because the method of delivering energy for these ablative procedures has not been fully developed. PMID- 8354834 TI - The editorial process. PMID- 8354835 TI - Remembering Keats in Rome. PMID- 8354836 TI - Same-day surgical admission. American College of Cardiology Cardiovascular Surgery Committee. PMID- 8354837 TI - Heart rate variability for risk stratification of life-threatening arrhythmias. American College of Cardiology Cardiovascular Technology Assessment Committee. PMID- 8354838 TI - Heart rate variability: disagreement on the markers of sympathetic and parasympathetic activities. PMID- 8354839 TI - Diastolic function of the nonfilling human heart. PMID- 8354840 TI - An inquiry into the fate of the transference in psychoanalysis. AB - Despite universal agreement about the importance of transference, there is no single, comprehensive, generally accepted explanation for the place transference occupies in clinical psychoanalytic theory. In this presentation, I trace the origins of some major trends prominent in theoretical controversy to their antecedents. Some seminal contributions which introduced important issues into the evolving theory of transference are highlighted; this is followed by a brief outline of the ideas of a representative sample of current theorists. This comparison of the appearance of fundamental evolutionary modifications of transference theory with present-day differences in theoretical emphasis leads to the identification of four persistent themes: (1) the nature of the influence of the patient's relationship with the analyst in the analytic experience, (2) how to account for the analyst's subjectivity and its role in the analytic process, (3) what weight to assign to the interpersonal dimension of the transference, and (4) differences among theoretical perspectives as reflected in the precise content of transference interpretations. Difficulties in the path of comparative evaluation of differences in theoretical accounts of the transference and its handling are noted. A few reasons for my adherence to the theory I prefer are mentioned solely for the purpose of underlining areas of controversy that require serious attention and further clarification. PMID- 8354841 TI - The couple's constructive and destructive superego functions. AB - Just as the couple becomes the repository of both partners' conscious and unconscious sexual fantasies and desires, and of their consciously and unconsciously activated internalized object relations, so does the couple activate both partners' conscious and unconscious superego functions. The interaction of the partners' superego over time results in the forging of a new system, which I am calling the couple's superego. The functions of the couple's joint superego structure is described, as are the symptoms of superego pathology in the couple's love life. The vicissitudes of gratitude and guilt, of stereotyping and conventionality, of deceptiveness and long-range destructive and self-destructive scenarios, are explored in the context of a spectrum reflecting the severity of joint superego pathology. A clinical case vignette illustrates some of these developments in a couple's life. PMID- 8354842 TI - Cathexes and their objects in the thought of Sigmund Freud. AB - This paper reexamines Freud's theory of "cathexis" (a quantity of motivational intensity invested in an object) in the light of recent developments in philosophy and cognitive psychology. Contrary to what is often thought, the quantitative element is defensible as a purely psychological idea. The notion of a cathexis is closely similar to the philosophical idea of an "intentional" state, which derives from Franz Brentano, Freud's teacher and mentor. Freud initially held the object of a cathexis always to be intrapsychic, a position which is untenable and which he largely abandoned after 1915, when he began (correctly) to take cathected objects generally to be persons or events, not their representations. His idea of a cathexis as "entering into" its object contains a valuable and neglected insight, which undermines the centrality of the distinction between the "outer" and "inner" realms of experience. This distinction should not be confused with the key distinction between "fantasy" and "actuality" with respect to cathectic objects. So-called "inner" (fantasy) objects are generally "inside" the mind in a metaphorical sense only. PMID- 8354843 TI - Recovering a repressed memory, and representational shift in an adolescent. AB - This case report focuses on the disappearance of a fixed pictorial iconic representation and transformation to symbolic (word) representation following the recovery of a repressed memory in a twelve-and-a-half-year-old after the first eleven months of psychoanalysis. There is a substantial body of psychoanalytic literature on the importance of language, naming or articulation of experiences associated with transformation of psychic structure (Fenichel, 1941; Glover, 1955; Kris, 1956a, 1956b; Werner and Kaplan, 1963; Schafer, 1976, 1978a, 1978b, 1980; Shapiro, 1979; Spence, 1982; Stern, 1989) and a relatively autonomous literature on the communicative representational power of children's play or visual portrayals (Piaget, 1962; A. Freud, 1947; Klein, 1964; Axeline, 1947; Esman, 1983; Neubauer et al., 1987; Krall, 1989). To our knowledge, there is no report of the structural effect of the recovery of a repressed traumatic experience, in this case, with subsequent parental confirmation of the traumatic event. PMID- 8354844 TI - Gender identity disorder in boys. Panel report. PMID- 8354845 TI - Learning from our unsuccessful cases. Panel report. PMID- 8354846 TI - The significance of religious themes and fantasies during psychoanalysis. Panel report. PMID- 8354847 TI - The difference between termination in psychotherapy and psychoanalysis. Panel report. PMID- 8354848 TI - Modulation by protein kinase C of arachidonic acid release from permeabilised myometrial cells of guinea pig uterus. AB - The effects of protein kinase C activation on phospholipase A2 and phospholipase C activity in permeabilised cultured myometrial cells from guinea pig uterus have been studied. Phospholipase A2 activity was followed by measurement of [3H]arachidonic acid release from [3H]arachidonic acid-prelabelled membrane lipids. [3H]Arachidonic acid release was stimulated by Ca2+ at 1-10 microM and by GTP gamma S at 1 microM to 1 mM in the presence of 10 microM Ca2+. The activation by calcium was enhanced 89.5 +/- 12.7% (P < 0.01) in the presence of 1 microM phorbol 12-myristate 13-acetate (PMA) and that by 1 microM GTP gamma S by 65.4 +/ 4.4% (P < 0.001). The PMA enhancement of arachidonic acid release was completely blocked by 3 microM staurosporine. Phospholipase C activation was followed by measurement of [3H]inositol polyphosphate production from [3H]inositol prelabelled membrane lipids. This was stimulated by Ca2+ at 0.1 and 10 microM and by 1 and 50 microM GTP gamma S. PMA at 1 microM caused a consistent reduction in the extent of Ca2+ and GTP gamma S-stimulated inositol polyphosphate production and 3 microM reversed the inhibitory action of PMA. The data are consistent with arachidonic acid release in permeabilised myometrial cells from guinea pigs reflecting in large part phospholipase A2 activation and with that pathway being stimulated by protein kinase C activation. They are also consistent with protein kinase C activation causing reduction in phospholipase C pathways in uterine myocytes, at least as measured by inositol polyphosphate release. PMID- 8354850 TI - A new technique for studying potential changes in nephrons of chick embryo kidneys in vivo. AB - To make the chick embryo accessible to electrophysiological measurements in its mesonephric kidney during the period between embryonic days (e.d.) 5 and 10, a special "chick-embryo-incubation bath" was constructed. It consists of an aerated chamber covering the egg and maintaining the gas exchange across the shell, and of a warmed reservoir of the incubation medium, into which the embryo is pulled out of the egg through a window in the shell. The two compartments are separated with a rubber membrane tightly fitting to the edges of the shell-window. The incubation medium contains a modified Krebs-Henseleit-Ringer solution and anesthetic Tricaine (Sigma). Access to the mesonephric nephrons is achieved by surgical excision of the body wall on the right side performed at e.d. 5. On average only about 35 percent of the operated embryos survive till the third day after surgery but during the next two days a mortality rate recedes to zero. The tolerance of short-term survival of embryos placed in the incubation bath was tested for up to 4 1/2 h. It was very good in embryos of age 5 to 7 e.d. as assessed by a steady heart rate and the presence of arterio-venous differences. A modified differential amplifier containing circuits for frequency compensation of the two channels was used for high-fidelity registration of voltage changes in the embryonic nephron with a single double-barrel microelectrode. PMID- 8354849 TI - A placental extract inhibits breathing induced by umbilical cord occlusion in fetal sheep. AB - Umbilical cord occlusion in the presence of adequate oxygenation induces continuous breathing and arousal in the chronic unanesthetized fetal sheep preparation. The mechanism responsible for this is unknown. We hypothesized that if a placental factor is responsible for the inhibition of breathing in the fetus, the administration of a placental extract while the fetus is breathing continuously after cord occlusion should reverse these changes. Thus, at about 10 min after the induction of continuous breathing by cord occlusion, we administered a placental extract and three subfractions separated by ultrafiltration to 14 chronically instrumented fetal sheep at 133 +/- 1 day gestation. The Krebs solution in which the placental extract was prepared was used as control. Within two minutes of the infusion of the whole placental extract in the carotid artery of the fetus, breathing output (integral of EMGdi x f) diminished in all experiments and was completely abolished in 15/17 (88%). Krebs solution had no effect on breathing. The infusion of subfractions of different molecular weight showed that the inhibition was primarily related to the subfraction between 3.5 and 10 kD. There were no significant changes in blood gas tensions, pH, blood pressure, and heart rate associated with the infusions of the extracts. The ECoG switched from low to high voltage in the majority of the experiments using whole extract and the subfraction 3.5 to 10 kD. These findings suggest that a placental factor, probably a peptide with a molecular weight between 3.5 and 10 kD, inhibits breathing in fetal life. PMID- 8354851 TI - Effect of the prenatal maternal environment on the control of breathing during non-rapid-eye-movement sleep in the developing lamb. AB - This study examines the effects of altering the prenatal maternal metabolic and hormonal environment via chronic cold exposure of under-fed ewes on developmental changes in breathing control of developing lambs. Breathing frequency and timing were measured during non rapid-eye-movement (non-REM) sleep in lambs born from either shorn or unshorn ewes after being maintained for at least one hour at warm (28-19 degrees C) and cool (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. Breathing frequency and oxygen consumption were significantly higher in 1 day old lambs born from shorn ewes compared with those lambs born from unshorn ewes, at both warm and cool ambient temperatures. In the shorn group breathing frequency decreased between 1 and 4 days of age and continued decreasing upto 30 days of age, during which period inspiratory and to a greater extent expiratory time, lengthened. Laryngeal "braking" of expiratory airflow was observed in more than 50% of lambs born from shorn ewes during non-REM sleep in the warm at 4, 14 and 30 days of age, and in the cold at 14 and 30 days of age. In contrast, lambs born from unshorn ewes showed no change in breathing frequency between 1 and 4 days of age, but a decrease was observed between 4 and 14 days of age, whilst laryngeal "braking" of expiratory airflow was rarely observed at any age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354852 TI - Postnatal development of nonshivering thermogenesis in rats: effects of rearing temperature. AB - A comparative chronological study (from 1 to 33 days post partum) was performed to establish the capacity for nonshivering thermogenesis (NST) in rats born and reared at 28 degrees C and at 16 degrees C. The resting metabolism measured at 33 degrees C was higher in the 16 degrees C rats than in the 28 degrees C rats from the 3rd day. When expressed per weight or per surface area units it was higher in 16 degrees C pups than in 28 degrees C pups until the end of the 3rd week. In fact the resting metabolism was significantly proportional to different powers of weight (W0.67 at 16 degrees C and W0.75 at 28 degrees C) during the suckling period. At birth, respiratory quotient (RQ) was the same in both groups (0.70); it increased slowly to the end of the 3rd week (about 0.80). During the 3rd week RQ was lower in 16 degrees C rats than in 28 degrees C animals. This indicates that 16 degrees C rats are more dependent on the milk supplied by their mother. After weaning there were no differences in RQ values (0.90). Rectal temperature was low in both groups on day 1 (about 32 degrees C). It increased until weaning when it stabilized at 37 degrees C. From day 1 to day 18, it was significantly lower in cold reared rats. The capacity for NST was measured by investigating the effect of an injection of norepinephrine (NE) on the metabolic rate at 33 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354853 TI - Imported Opisthorchis viverrini and parasite infections from Thai labourers in Taiwan. AB - In order to determine the prevalence of intestinal parasites among labourers from Thailand in Taiwan, the stool samples from 1364 Thai labourers were examined by the formalin-ether concentration method and 18.0% were found to be infected with one or more parasites. The infection rates of hookworm, Opisthorchis viverrini, Strongyloides stercoralis, Enterobius vermicularis, Ascaris lumbricoides, Hymenolepis nana, Capillaria philippinensis, Schistosoma japonicum, Echinostoma sp., Entamoeba coli, Giardia lamblia, and Entamoeba histolytica, were 7.6%, 7.0%, 3.2%, 0.5%, 0.3%, 0.1%, 0.1%, 0.1%, 0.1%, 0.4%, 0.2%, and 0.1% respectively. The prevalence was highest among the 21-25 age group (24.8%). Among the 245 infected persons, 91% were infected with one parasite, 8% with two parasites and 1% with three parasites. The finding that parasitic infections are prevalent among Thai labourers demonstrates the need for control measures in foreign labourers in Taiwan and further studies to determine the susceptibility of O. viverrini to the snail hosts of Clonorchis sinensis. PMID- 8354854 TI - A first instance of human philophthalmosis in Israel. AB - Conjunctivitis due to the trematode Philophthalmus in a 13-year-old Israeli girl is described. A single worm, probably a mature Philophthalmus palpebrarum, was detected on the palpebral conjunctiva of the upper eyelid of the right eye. Removal of the worm resulted in rapid abatement of the ocular symptoms. This is the first documentation of human philophthalmosis in Israel. PMID- 8354855 TI - Distribution of some elements in hydatid cysts of Echinococcus granulosus from buffalo (Bubalus bubalis). AB - Distribution of some elements during development of endogenous daughter (hydatid) cysts of Echinococcus granulosus of buffalo origin was determined by atomic absorption spectrophotometry. These analyses showed that the distribution of copper and cobalt was highest in the smallest cysts. These elements gradually decreased in the cysts as they enlarged. The distribution of zinc, iron and manganese was very high in the smallest cysts in comparison to copper and cobalt, but these three elements decreased greatly in larger cysts. Iron and manganese were the only two elements found in very high concentrations in "thin-walled" cysts. Like all other elements both calcium and magnesium decreased as the cysts increased in size. In the thin-walled cysts magnesium increased by four times initially and this was followed by a two-fold "influx" of calcium in the "white spots" in the above cysts. The significance of these findings is discussed in relation to earlier works. PMID- 8354856 TI - The prevalence and intensity of infection with helminth parasites in Mus spretus from the Setubal Peninsula of Portugal. AB - The results of a 5 year study of helminth parasites of Mus spretus, are reported. Six nematode and 5 cestode species were identified but no helminth showed 100% prevalence in M. spretus, the most commonly encountered nematode and cestode species being Syphacia obvelata (46.6%) and Taenia taeniaeformis (22.4%). Among the more unusual helminth species identified was Eucoleus bacillatus, a capillariid nematode inhabiting the stomach musculature. This species was identified in 3 of the 5 years of the study. The results are discussed in the broader context of previous studies and the epidemiology of rodent helminth infections in general. PMID- 8354857 TI - Onchocerciasis in British cattle: a study of the transmission of Onchocerca sp. in north Wales. AB - The transmission of bovine Onchocerca spp. in Britain was investigated by studying the Ceratopogonidae and Simuliidae which attacked bait cattle between April and October at two sites in North Wales, where either Onchocerca lienalis and O. gutturosa (Cynwyd), or O. lienalis alone (Pentrefoelas) occurred. Based on the relative abundance of each species, their seasonal variation in abundance and preferential feeding sites on cattle, the presence of Onchocerca sp. infective larvae and the development of patent infections in bait cattle, vectors were identified as Simulium ornatum s.1. at Pentrefoelas and S. reptans at Cynwyd (0.5% and 1.5% of parous flies infective, respectively). There was no significant difference between the lengths of the infective larvae from vectors at either site (Pentrefoelas: mean = 543.5 microns, SD = 29.45; Cynwyd: mean = 550.86 microns, SD = 35.26; p > 0.1), which were consistent with descriptions of O. lienalis. The identity of a vector for O. gutturosa was not determined and the role of certain candidates is discussed. In this respect, the absence of Culicoides nubeculosus was notable. Transmission of Onchocerca sp. was limited to a short period of about 8 weeks, by a combination of vector abundance and parasite uptake from dermal skin layers, and a mean daily temperature requirement of 15 degrees C or more for complete parasite development in the vector. The effect of this temperature restriction in relation to the geographical distribution of the two species is discussed. PMID- 8354858 TI - Antagonistic effect of predacious Arthrobotrys fungi on infective Haemonchus placei larvae. AB - Laboratory experiments were performed to investigate the ability of isolates from the predacious fungus species Arthrobotrys conoides (one isolate) and Al. robusta (four isolates) to trap and kill infective Haemonchus placei larvae. Three groups for each isolate were formed: group 1, fungi and infective larvae; group 2, fungi; group 3, infective larvae. There were statistically significant differences (P < 0.05) between the antagonistic effects of three isolates of A. robusta, but there was no such difference between the isolate of A. conoides and isolates of A. robusta. This result indicates that there can be a variation in the predatory capacity of different isolates within a single fungus species. After 20 days of assay, there was greater recuperation of infective H. placei larvae in group 3 compared to group 1. PMID- 8354859 TI - Histopathology of the small intestinal mucosa in Nematodirus spathiger infection in rabbits. AB - Rabbits were experimentally infected with two levels (5000 and 17,000) infective larvae of Nematodirus spathiger. Histological (villus length, mucosa to serosa ratio, crypt surface) and biochemical (protein content, alkaline phosphatase and leucine aminopeptidase activities) measurements relating to the small intestinal mucosa were examined along the entire length of the organ. In the proximal intestine, the presence of worms was associated with villus abrasion, increased crypt surface and decreased alkaline phosphatase and leucine aminopeptidase activities. Conversely, beyond the main site of infection in the distal small intestine, some signs of hypertrophied villi and crypts were noted without any changes in enzyme activities. These distal variations were similar to those previously described in experimental Trichostrongylus colubriformis infections of rabbits. These results tend to confirm the use of the rabbit as an experimental model to study Nematodirus infection. They also suggest that the distal adaptive process in the nematode-parasitized small intestine could occur independently of the worm species. PMID- 8354860 TI - Changing chemosusceptibility in the second-stage larvae of Toxocara canis by long term incubation. AB - Second-stage larvae of Toxocara canis were maintained in vitro for one year. Susceptibility of the larvae to drugs was evaluated by means of minimal larvicidal concentration (MLC) and larval bursting percentage. MLCs of citral and decanoic acid were almost constant throughout all stages of incubation. However, bursting percentage markedly varied within the first 20 weeks of incubation. Therefore, while larvae are available for use in the MLC assay at any stage of incubation, those beyond the first 20 weeks after incubation should be used for the bursting assay to obtain reproducible results. PMID- 8354861 TI - Density-dependent effects on establishment of Necator americanus and Ancylostoma ceylanicum. AB - The relationships between the number of infective larvae (L3s) to which animals were exposed and the establishment of A. ceylanicum and N. americanus in hamsters were examined. There was no evidence of density-dependent constraints on the establishment of A. ceylanicum in the range 10-1000 larvae, but an experiment in which the range was extended to 1500 L3s gave a significant negative correlation between the magnitude of the infecting dose and percentage establishment. Even so the percentage reduction was relatively small, approximating to 0.89% per 100 larvae administered, and in practice density-dependent constrains on establishment are unlikely to affect experiments with this species in which much lower doses (< 250 L3) are generally employed. The range of doses for N. americanus L3s was smaller (10-400). Of the four experiments reported, two gave a significant reduction of establishment with increasing dose and two did not. When the data was split into low doses (< 100 L3s) and high doses (> 100 L3s), falling establishment with increasing dose was only detected in the lower dose range. There was no difference in the establishment when doses of 100 L3s were compared with 250 or 400 L3s. On balance, it was concluded that density-dependent constraints on establishment of N. americanus in hamsters were not marked and would have little significant effect on experiments utilizing fewer than 200 L3s (approximately 7.6% reduction between 10 and 200 L3s). These results are discussed in relation to host regulation of hookworm burdens. PMID- 8354862 TI - Infectivity, growth and distribution of preovigerous adults of Echinostoma caproni in ICR mice. AB - All 23 6-8-week old outbred female ICR mice, each fed 100 metacercarial cysts of Echinostoma caproni, were infected on days 2, 4, 6, and 8 postinfection (PI) with a mean of 45 worms/host. To examine worm distribution in the mouse, the small intestine was divided into five equal sections (segments 1-5 beginning with the pylorus). Worms were found mainly in segments 3 and 4 and were never found in segment 1. Mean body area of worms fixed in 10% neutral buffered formalin (NBF), hot alcohol-formalin-acetic acid (AFA) and aceto-carmine increased slowly until day 4 and then rapidly until day 8 PI. There was a significant difference in the mean body area of worms fixed in hot AFA, NBF, and aceto-carmine on all days except 4 and 6. Distinction of the ovary and ootype was apparent by day 6 and uterine cooling was observed by day 8 PI. Only 2 of 50 worms showed eggs in the uterus on day 8 PI. PMID- 8354863 TI - Strongyloides ratti: dissociation of immunological memory of the protection against tissue migrating larvae and intestinal adult worms in mice. AB - Immunological memory generated by infection with S. ratti was studied separately in the migratory and intestinal phases in mice. Protection against reinfection in the migratory phase was 96-98% at 2 weeks but significantly decreased to 60% at 12 weeks after the primary infection. However, protection in the intestinal phase was 96% even 12 weeks after the primary infection. Recall of immunity against the intestinal phase persists for longer than that against the migratory phase in mice. PMID- 8354864 TI - Vaccination with hatched but non-activated, non-viable oncospheres of Taenia taeniaeformis in rats. AB - The usefulness of hatched but non-activated oncospheres as a candidate vaccine was evaluated using a Taenia taeniaeformis/rat system, since preparation of these oncospheres in vitro is known to be very simple. The findings were: (1) rats vaccinated with non-viable oncospheres became completely resistant to challenge infection; (2) intra-venous injection was the most effective to induce complete resistance; (3) a single oncosphere was sufficient to induce complete resistance in infected rats, whereas approximately 50 and 500 non-viable oncospheres were required to evoke strong and complete resistance, respectively, in vaccinated rats. The usefulness of non-viable oncospheres without adjuvant is discussed. PMID- 8354865 TI - Aspergillus terreus during hospital renovation. PMID- 8354866 TI - Environmental contamination with Staphylococcus aureus and outbreaks: the cause or the effect? PMID- 8354867 TI - An outbreak of mupirocin-resistant Staphylococcus aureus on a dermatology ward associated with an environmental reservoir. AB - OBJECTIVE: To investigate a cluster of mupirocin-resistant Staphylococcus aureus on a dermatology ward. DESIGN: An outbreak of mupirocin-resistant S aureus was noted on the dermatology ward during a prospective epidemiologic study of methicillin-resistant S aureus (MRSA) and borderline methicillin-susceptible S aureus (BMSSA). Pulsed-field gel electrophoresis (PFGE) of whole-cell DNA digested with Sma I was used as a marker of strain identity. SETTING AND PATIENTS: An 850-bed university hospital with a 12-bed inpatient dermatology ward. Most patients have severe, exfoliating dermatologic disorders. RESULTS: MRSA or BMSSA were isolated from 13 patients on the dermatology ward over a 14 month period. Eleven of these isolates (84.6%) were mupirocin-resistant. Nine isolates were present on admission (81.8%); 8 of these patients had been hospitalized on the same ward within the last two months. Nasal and hand cultures from 36 personnel were negative for mupirocin-resistant MRSA or BMSSA. Extensive environmental culturing revealed that a blood pressure cuff and the patients' communal shower were positive for mupirocin-resistant BMSSA. PFGE of all mupirocin-resistant isolates demonstrated that the nine patients and both environmental sources had identical DNA typing patterns. INTERVENTIONS: Changing of blood pressure cuffs between patients and more stringent cleaning of communal areas was initiated. Repeat environmental cultures were negative. CONCLUSIONS: S aureus is not usually associated with an environmental reservoir; however, these patients all had severe desquamation, which may have prolonged environmental contamination. PMID- 8354868 TI - Trends in antimicrobial utilization at a tertiary teaching hospital during a 15 year period (1978-1992). AB - BACKGROUND: Antimicrobials are a major part of hospital pharmacy budgets and must be considered in resource planning and spending projections. Logically, trends in antimicrobial usage should be linked to trends in resistant pathogens. OBJECTIVE: To examine long-term trends in antimicrobial use over a 15-year period (1978 to 1992) and contrast them with changes in pathogens causing nosocomial bacteremia. SETTING: A 900-bed, tertiary care teaching hospital. METHODS: Pharmacy records were reviewed to identify parenteral antimicrobial agents administered to adult inpatients. Results were expressed in average daily adult doses per 1,000 patient days. RESULTS: Chloramphenicol use decreased, while use of penicillin G, antistaphylococcal penicillins, first-generation cephalosporins, and aminoglycosides remained relatively stable. In contrast, there was a sharp increase in the use of second- and third-generation cephalosporins (7-fold and 6.5-fold increase, respectively), vancomycin (161-fold increase), metronidazole (32-fold increase) and amphotericin B (35-fold increase). The proportion of nosocomial bacteremias due to methicillin-resistant gram-positive bacteria rose, but gentamicin resistance in gram-negatives remained at low levels. During the past 14 years, the percentage of patients receiving at least one parenteral antimicrobial rose from 23% to 44%. Among patients receiving antimicrobials, the average number of different agents used per patient increased from 1.8 to 2.1. CONCLUSIONS: If newer agents were available, use of older agents usually declined. If newer alternatives were not available, use of older agents rose sharply. The increased use of antimicrobials in adults was related to the expanded proportion of patients receiving these agents. PMID- 8354869 TI - A prospective randomized trial comparing manual and automated endoscope disinfection methods. AB - OBJECTIVE: To compare the efficacy of endoscope disinfection using automated and manual systems. DESIGN: Prospective randomized trial. SETTING: A 1,000-bed tertiary care referral center. METHODS: All endoscopes underwent a three-stage decontamination process including brushing and cleaning with water and detergent, manual or automated disinfection with 2% glutaraldehyde, and 70% alcohol rinse with forced air drying. Cultures were obtained from endoscopes from both groups before and after alcohol rinse and then after overnight storage. RESULTS: Cultures from 8/30 (27%) automated and 11/30 (37%) manually disinfected (P = 0.58) endoscopes grew gram-negative bacteria and/or nontuberculous mycobacteria before the alcohol rinse. After alcohol rinse, 3 (10%) of 30 automated and 8 (27%) of 30 manually disinfected endoscopes remained contaminated (P = 0.28). Manually disinfected endoscopes were contaminated more frequently with coliform bacteria, whereas endoscopes undergoing automated disinfection were more frequently contaminated with nontuberculous mycobacteria, but the differences were not statistically significant. After alcohol rinse and forced air drying, there was no difference in contamination rates between freshly disinfected endoscopes and those stored overnight (7/30 (23%) versus 4/30 (13%), P = 0.50). Colonoscopes and duodenoscopes were contaminated more often than gastroscopes (P = 0.00001). CONCLUSION: The persistent endoscope contamination after manual and automated disinfection indicates the importance of developing more reliable and effective disinfection methods. PMID- 8354870 TI - Evaluation of a rapid readout biological indicator for flash sterilization with three biological indicators and three chemical indicators. AB - OBJECTIVE: Flash sterilization is most commonly used for emergency sterilization of unwrapped items in a gravity displacement sterilizer for three minutes. Sterilization quality assurance is monitored by biological indicators that require a 24-hour incubation prior to reading. In this study, we compared a new biological indicator that provides results within 60 minutes with three conventional, 24-hour biological indicators for monitoring flash sterilization and three chemical indicators. DESIGN: Conventional biological indicators tested included the conventional Attest 1261, Proof Flash and Assert, while the rapid readout indicator tested was Attest 1291. Attest Rapid Readout detects the presence of a Bacillus stearothermophilus enzyme by reading a fluorescent product that is produced by the enzymatic break-down of a nonfluorescent substrate. Chemical indicators tested included Comply, Incheque, and Thermalog S. Survival at 132 degrees C in a gravity displacement sterilizer was measured by media color change after incubation for 24 hours at 56 degrees C for the three conventional biological indicators, fluorescence at 60 minutes for the Attest Rapid Readout biological indicator, and color change for the chemical indicators. Each exposure time was replicated four times with 10 of each biological and chemical indicator per run. RESULTS: The conventional biological indicators (Attest, Proof Flash, and Assert) had 90%, 48%, and 40% spore survival at two minutes exposure; 23%, 3%, and 0% at three minutes exposure; and 3%, 0%, and 0% at four minutes exposure respectively. The Attest Rapid Readout biological indicator had 88%, 33%, and 0% enzyme activity detectable at 2, 3, and 4 minutes exposure. The chemical indicators Comply, Incheque, and Thermalog S revealed sterilization failure rates of 100%, 100%, and 100% at 0 minutes exposure; 100%, 100%, and 45% at one minute; 0%, 0%, and 28% at two minutes exposure; 0%, 0%, and 18% at three minutes exposure; and 0%, 0%, and 0% at four minutes exposure, respectively. CONCLUSION: The sensitivity of the Attest Rapid Readout parallels the conventional biological indicators. These data suggest that a 60-minute rapid readout biological indicator is equivalent to the 24-hour biological indicators. If further studies demonstrate that a four-minute flash sterilization cycle provides a needed safety margin to ensure sterilization, then consideration should be given to requiring a four-minute flash sterilization cycle. Chemical indicators were too sensitive to the processing conditions (eg, steam) and are inadequate to ensure adequate sterilization. PMID- 8354871 TI - Diarrhea among residents of long-term care facilities. AB - Diarrhea is a common problem among residents of long-term care facilities. Although the etiology of many cases of diarrhea will be noninfectious, the approach to managing all patients with diarrhea must include assuring the adequacy of hydration and controlling the spread of infection. The latter issue is especially critical in nursing homes where a large proportion of patients can became ill over a several-day period during an outbreak. Although most outbreaks of diarrhea are viral in origin, bacterial outbreaks can lead to hospitalization and even death. Increasing awareness among physicians and infection control practitioners of the correct approaches to investigating and managing cases of diarrhea among nursing home patients is necessary because the magnitude of this problem will grow as the number of individuals being cared for in long-term care facilities increases. PMID- 8354872 TI - Managing occupational exposures to HIV-1 in the healthcare workplace. PMID- 8354873 TI - In vitro autoradiographic visualization of occupied estrogen receptors in the rat brain with an iodinated estrogen ligand. AB - Methods have been developed for the selective measurement of occupied estrogen receptors (ER) in brain tissue sections. Cryostat sections of unfixed tissue were incubated with radiolabeled estrogen at physiological temperatures, displacing endogenous receptor-bound estrogen by radioligand and thereby allowing the receptor complexes to be visualized autoradiographically after washing to remove nonspecifically bound steroid. The resultant autoradiographs were analyzed by computer-assisted densitometry. Synthetic 11 beta-methoxy-substituted radiolabeled estrogens gave the best autoradiographic images, as a result of reduced nonspecific labeling, although [3H]-estradiol was also used successfully. With the synthetic ER ligand 11 beta-methoxy 16 alpha-[125I]-iodo-estradiol, exposure times of less than 24 hr generated acceptable autoradiographs; with 3H labeled estrogens, exposures of 3 months or more may be required. The method is sufficiently sensitive to detect physiological changes in ER occupation and to allow determination of receptor affinities and saturation binding capacities in discrete cell groups identified in sections from individual animals. PMID- 8354874 TI - Developmental expression of SP-A and SP-A mRNA in the proximal and distal respiratory epithelium in the human fetus and newborn. AB - We used immunolocalization and in situ hybridization to determine the distribution of SP-A and SP-A mRNA in lungs of human fetuses and normal newborn infants. Early in the second fetal trimester a few immunostained cells were observed in tracheal epithelium, often in mucosal folds near the origin of submucosal gland ducts. Non-mucous tracheal gland cells were immunostained for SP A as they became differentiated. Expression of SP-A mRNA was similar to that of immunolocalization in the second trimester. Immunostained cells and SP-A mRNA also appeared about the same time in gestation in isolated cells of bronchial epithelium and glands. SP-A mRNA was seen in bronchiolar cells and pre-Type II cells lining terminal airways of fetuses at 19-20 weeks of gestation. Only in liveborn infants did cells of bronchioloalveolar portals and mature Type II cells contain SP-A mRNA or immunostain for SP-A. In postnatal infants, luminal material was also stained for SP-A. Although some alveolar macrophages contained immunoreactive material, SP-A mRNA was never detected. The abundance of SP-A in tracheal and bronchial glands and epithelium of conducting airways supports the importance of non-surfactant-associated functions for SP-A and may be related to a role in host defense. PMID- 8354875 TI - Validation of immunohistochemical quantification in confocal scanning laser microscopy: a comparative assessment of gap junction size with confocal and ultrastructural techniques. AB - Confocal scanning laser microscopy (CSLM) is increasingly being used to image antibody-labeled structures visualized with a fluorescent secondary antibody. Such digital images are routinely stored on computer and are well suited to quantitative analysis. Although theoretical aspects of CSLM imaging and resolution are well defined, information is lacking on the relationship observed between measurements of fluorescent antibody-labeled structures and the size of the same structures as determined by electron microscopy (EM). In the present study we examined this relationship for the cardiac gap junction. Data on the size of immunofluorescent-labeled gap junctions were acquired by two methods of analysis from CSLM images and compared statistically with measurements of gap junction size obtained by freeze-fracture EM. The freeze-fracture data were compared before and after exclusion of small junctions, corresponding to those that theoretically would not have been detected in CSLM analysis. The data obtained by the different methods were similar but not identical, reflecting the advantages and limitations of each technique. However, the comparison did indicate that with appropriate sample preparation and orientation, accurate and rapid analysis can be achieved by CSLM, particularly when digital semi-automated techniques are employed. PMID- 8354876 TI - Glycoproteins of mouse vaginal epithelium: differential expression related to estrous cyclicity. AB - We used lectin overlay blotting and SDS-PAGE to analyze the estrous cycle specific expression of mouse vaginal epithelial glycoproteins. Seven lectins chosen for their differential carbohydrate-binding specificity revealed 15 glycoproteins that showed cycle-related expression. Each lectin had a unique binding pattern different from the patterns revealed by other lectins. However, several estrous cycle phase-specific glycoproteins reacted with more than one lectin. The most prominent of these glycoproteins (M(r) 92-95 KD) was weakly expressed in late diestrus and fully expressed only in proestrus, coincident with the transformation of two superficial layers of vaginal squamous epithelium into mucinous cuboidal cells. Electron microscopic lectin histochemistry revealed the glycoproteins in the mucinous granules of surface cuboidal cells and in the lumen of the vagina. Our results illustrate the complexity of glycoconjugate synthesis in mouse vagina and reveal the distinct cycle-specific patterns of individual glycoprotein expression. These cyclic glycoproteins could serve as vaginal biochemical markers for the specific phases of the estrous cycle. PMID- 8354877 TI - Secretion of chondroitin sulfate from embryonic epidermal cells in Xenopus laevis. AB - We examined proteoglycans (PGs) in amphibian epidermal cells by immunofluorescence microscopy. Immunoelectron microscopy with pre- and post embedding methods, combined with HRP- or gold-conjugated secondary antibody, revealed ultrastructural localization of glycosaminoglycans (GAGs). Embryonic epidermis secretion granules in Xenopus laevis contained chondroitin 6-sulfate and unsulfated chondroitin. Immature secretion granules were also labeled with anti-chondroitin 6-sulfate and anti-chondroitin. A step-wise digestion experiment on chondroitinase ABC revealed that fine filaments in the secretion granules were chondroitin sulfate chains. Inhibition experiments with brefeldin A revealed that the life of a secretion granule was 5-10 hr, suggesting that GAG secretion from embryonic epidermis is routed through a regulated pathway. PMID- 8354878 TI - Expression of decorin mRNA in the nervous system of rat. AB - A rat cDNA clone (pCD67) isolated from a cDNA library of regenerating sciatic nerve by differential hybridization screening revealed 75% homology on the nucleic acid level and 81% homology (including conservative amino acid changes) to the deduced amino acid sequence of the core protein of human dermatan/chondroitin sulfate proteoglycan decorin (PGII, PG40, PG-S2). Two transcripts of 1.3 and 1.75 KB very similar in size to the two decorin mRNA species previously identified in connective tissue were detected by Northern blotting in both normal and injured sciatic nerve and in the mature and embryonic rat brain. The steady-state level of the decorin 1.3 KB mRNA was very much higher in peripheral nerve than in the central nervous system or in other non-neural tissues (skeletal muscle, heart, colon, kidney). In situ hybridization experiments indicated that decorin mRNA is expressed by Schwann cells and vascular cells in peripheral nerve. In the spinal cord the ventral horn motor neurons and other neurons in gray matter showed specific hybridization signals. Furthermore, in situ hybridization indicated decorin expression in Purkinje neurons and cells of the molecular layer in cerebellum, and in neurons of the primary olfactory cortex and brainstem (pons). Our data clearly demonstrate decorin mRNA expression in distinct neural cell populations, suggesting yet unknown functions of this proteoglycan in the peripheral and central nervous system. PMID- 8354879 TI - Silver-enhanced diaminobenzidine-sulfide (SEDS): a technique for high-resolution immunoelectron microscopy demonstrated with monoamine immunoreactivity in monkey cerebral cortex and caudate. AB - A common frustration of immunoelectron microscopy (IEM) is the density of the 3,3'-diaminobenzidine (DAB) label, which obscures intracellular details of labeled structures. To overcome this problem, a silver enhancement protocol was developed which leaves silver deposits on very low levels of DAB. The resulting label is composed of easily visualized punctate silver deposits, localized in processes with little or no detectable DAB. This technique incorporates several modifications into previously described methods for silver enhancement of DAB. The principal innovation is to pretreat the DAB label with sodium sulfide before silver enhancement, which substantially increases the sensitivity of the silver enhancement. In addition, cysteine was used in place of thioglycolic acid to suppress tissue argyrophilia, allowing use of both glutaraldehyde- and paraformaldehyde-fixed tissue without degradation of ultrastructure. We demonstrate this technique with dopamine, norepinephrine (NE), and serotonin (5HT) immunoreactivity in monkey prefrontal cerebral cortex and with dopamine immunoreactivity in the anterior caudate. The punctate label allows essentially unobscured visualization of the intracellular details and cell membranes of these monoamine axons. Whereas 5HT axons formed small asymmetric synapses, dopamine and NE axons typically formed small symmetric synapses with notably subtle membrane specializations. It is likely that these are often obscured by conventional DAB labeling. The use of several preparations indicates that this technique will be useful with a variety of antibodies. It might also provide an attractive alternative to colloidal gold, especially with glutaraldehyde-fixed tissue which is not easily penetrated by gold particles. PMID- 8354880 TI - Histamine-storing cells in the oxyntic mucosa of the rat stomach: a transmission electron microscopic study employing fixation with carbodiimide. AB - We studied the distribution of histamine (HA) immunoreactivity in endocrine cells of the acid-producing mucosa in rat stomach with pre-embedding immunoelectron microscopy (IEM) using an antiserum against HA. Four fixation modifications were compared to optimize the ultrastructural morphology and staining pattern with the antisera produced against carbodiimide-conjugated HA. Fixation with 4% 1-ethyl 3(3-dimethyl-aminopropyl) carbodiimide (EDCDI) combined with both 4% paraformaldehyde and 0.1% glutaraldehyde gave superior results compared with EDCDI alone. Enterochromaffin-like (ECL) cells were easily distinguished from other endocrine cells in optimally fixed samples. The peroxidase end-product was distributed within the cytoplasm surrounding the vesicles of the ECL cells. ECL cells comprised about 75% of all endocrine cells, and about 90% of them were HA immunoreactive (HA-IR). No other HA-IR cell types were identified by EM in the basal half of the oxyntic region of rat gastric mucosa. The results suggest that a combination of EDCDI and aldehydes is suitable for IM demonstration of HA in cells. ECL cells from a predominant portion of endocrine cells in the oxyntic glands and may constitute the only significant non-mast cell store of HA in rat gastric mucosa. PMID- 8354881 TI - In situ fluorescent visualization of nucleolar organizer region-associated proteins with a thiol reagent. AB - Nucleolar organizer regions (NORs) are nucleolus-forming rDNA loops associated with argyrophil proteins, the amount of which varies according to the proliferative state of the cell. It has been presumed that the nucleolar protein related thiol groups may have a role in selective silver staining. We investigated the nuclear thiol distribution with a fluorescent thiol reagent, coumarinyl-phenyl-maleimide (CPM) in human K-562 myeloblast cultures and found that SH group-related fluorescence was brightest in the area of nucleoli, which became highly selective after RNAse digestion. A remarkable co-localization of AgNOR silver reaction and CPM fluorescence was observed, although occupation of the SH groups by CPM did not prevent the silver staining. We applied the stain to dual-parameter flow cytometry in combination with DNA content measurements, which provide further information on nucleolar function and changes in experimental and pathological specimens. PMID- 8354883 TI - Measurement of DNA content and of tritiated thymidine and bromodeoxyuridine incorporation by the same cells. AB - We tested a method of measuring DNA content (Feulgen) and tritiated thymidine ([3H]-T) and bromodeoxyuridine (BrdU) incorporation by the same cell. Initial experiments showed that Feulgen hydrolysis denatured the DNA of fixed cells sufficiently to allow detection of incorporated BrdU with monoclonal antibodies. MCa-11 cells were then double-labeled with [3H]-T and BrdU, placed on slides, and Feulgen stained. Next, absorption cytometry was performed to measure the DNA content of randomly selected cells. Feulgen staining and the development and removal of either the [3H]-T or the BrdU grains after DNA measurements did not interfere with subsequent detection of the grains from the other label, and BrdU and [3H]-T can be used reliably in combination for identification of S-phase cells. This method may eventually allow the use of microscope-based image analysis to selectively measure the DNA contents and the BrdU/[3H]-T labeling of non-transformed stromal and cancer cells in solid tumors, thereby providing new insights into the growth kinetics of these heterogeneous cell populations. PMID- 8354882 TI - A novel hinge system and incubation chamber for emulsion-coated coverslip autoradiography. AB - We describe an emulsion-coated coverslip autoradiographic technique for large (50 x 50 mm) sections of monkey or human brain. The technique uses adhesive-backed, teflon-reinforced aluminum foil as a flexible hinge that allows the coverslip to swing away from the slide so that the emulsion and tissue can be processed independently. We also describe a plexiglas incubation chamber that allows two slides with coverslips folded away to be processed back-to-back in 5 ml of reagent solution. In general use, the chamber minimizes the volume of solution needed to cover large slide-mounted sections and is ideal for radioligand or immunohistochemical reactions that use expensive reagents. For autoradiography, the chamber greatly facilitates independent processing of the emulsion and tissue section. Together, the foil-hinge method and incubation chamber virtually eliminate the major technical pitfalls of previous emulsion-coated coverslip methods. Moreover, they facilitate combination of histochemical or immunocytochemical staining with autoradiographic localization of neurotransmitter receptors in the same tissue section. This is demonstrated by thioflavin S staining of neuritic plaques and tangles and autoradiographic localization of serotonin 1A receptors in sections of Alzheimer disease brain. PMID- 8354885 TI - Enhancement of immunoassay sensitivity by molecular modification of competitors. AB - The potential of weak competitors to enhance the sensitivity of competitive immunoassays is described. Several triazine derivatives have been analyzed for their use as competitors. Their binding properties were determined using an enzyme-linked immunosorbent assay (ELISA) with a monoclonal antibody specific to triazines. Selected derivatives were immobilized onto the surface of a fibre optic sensor and atrazine was determined in a competitive manner using a fluorescein-labelled antibody. Using the weak binding competitor 11-(4-ethylamino 6-methylthio-s-triazine-2-yl)undecanoic acid (TE11S) the detection limit for atrazine could be lowered 100-fold in comparison to 2-aminohexylamino-4 ethylamino-6-isopropylamino-s-triazine (AHA), the previously used competitor. PMID- 8354884 TI - Chicken egg antibodies for immunohistochemical labeling of growth hormone and prolactin in bovine pituitary gland. AB - We describe the production of polyclonal chicken antibodies specific for bovine growth hormone (bGH) and prolactin (PRL). Antibodies were generated by immunization of laying hens with recombinant bGH (rbGH), pituitary derived bGH (pbGH), and ovine PRL (oPRL). After the lipoprotein fraction was removed by dextran sulfate precipitation the antibodies were isolated from the egg yolks by ammonium sulfate precipitation. Immunization with rbGH and oPRL generated large amounts of specific antibodies, as revealed by ELISA and Western blot analysis. Antibodies against pbGH showed pronounced crossreactions with oPRL. The antibodies against rbGH and oPRL were well suited for sensitive and specific labeling of the GH- and PRL-synthesizing cells in bovine pituitary glands by immunohistochemistry. In addition, a quick and sensitive procedure for demonstration of both bGH- and PRL-synthesizing cells in a single paraffin section by double immunohistochemistry is presented. The chicken anti-bGH antibodies showed excellent results in combination with rabbit anti-PRL antibodies. The main advantage of avian antibodies in double immunostaining methods is the lack of crossreactions between avian antibodies and mammalian immunoglobulins and receptors which bind to the crystalline fragment of mammalian immunoglobulins (Fc receptors). PMID- 8354886 TI - Two-site ELISA for quantification of the terminal C5b-9 complement complex in plasma. Use of monoclonal and polyclonal antibodies against a neoantigen of the complex. AB - A quantitative ELISA procedure using monoclonal and polyclonal antibodies against neoantigens of the terminal C5b-9 complement complex has been developed. The ELISA was demonstrated to be both sensitive and reproducible. The normal range for C5b-9 determinations, defined as 2.5-97.5% interval of the values obtained in 76 healthy blood donors, was 3.12-10.3 AU/ml. The presence of rheumatoid factor did not affect the determination of C5b-9 as demonstrated by immunoabsorption studies. PMID- 8354887 TI - A fluorometric assay for the quantitation of cell adherence to endothelial cells. AB - A rapid quantitative fluorometric assay was developed for analysis of leukocyte adherence to endothelial cells. In this method adherent monocyte and T cell lines are labeled with the fluorescent dye Calcein AM without affecting cell function. Following coincubation with endothelial cells and gentle washing to remove nonadhering cells, the relative fluorescence intensity of the adhering cells is determined with a fluorescence microtiter plate reader. Relative fluorescence intensity increases linearly with cell number over a wide range of concentrations. By comparison of fluorescence levels of adhering cells to a dilution series of labeled cells alone, the number of adhering cells can be determined. We compared this adherence assay with the 51Cr-labeling assay and found comparable adherence. However, we found the fluorescence assay to be more rapid as the use and special handling of radioactive material is eliminated. To monitor the reliability and reproducibility of this method, we followed the adherence of Calcein AM-labeled THP-1 cells, a human monocytic cell line, to human endothelial cells treated with interleukin-1. PMID- 8354888 TI - Immunoassay reagents for psychoactive drugs. II. The method for the development of antibodies specific to imipramine and desipramine. AB - Imipramine and desipramine were structurally modified by the attachment of spacer arms to the aromatic ring which were subsequently attached to bovine serum albumin. This approach utilized novel spacer arms and conjugation methods. This method yielded antisera with excellent selectivity and good titers. Rabbits were used to raise the antisera and the antibodies produced were characterized with respect to their cross-reactivity with imipramine, desipramine and hydroxy metabolites as well as selected structurally related compounds. PMID- 8354890 TI - A europium fluoroimmunoassay for measuring binding of antigen to class II MHC glycoproteins. AB - A dissociation-enhanced lanthanide fluoroimmunoassay employing europium streptavidin and time-resolved fluorimetry was developed to measure binding of biotin-labeled peptides to class II MHC proteins. Binding of biotin-peptides as measured by this assay was saturable and inhibited in the presence of unlabeled peptide. Background fluorescence was minimal and there was a direct relationship between signal and biotin-peptide/class II complex concentration from 1.3 pmol to less than 1 fmol total class II. The sensitivity of the assay and the ability to selectively capture specific class II proteins from detergent lysates of cells with solid phase mAb made it possible to measure formation peptide/class II complexes in live APC cultured with biotin-labeled insulin. This assay is expected to be useful for routine measurement of peptide/class II binding and biochemical analysis of Ag processing events. PMID- 8354891 TI - The optimisation of a novel iodide microassay and its application in an immunoassay for human antibody levels in serum. AB - Radioactive iodine has been used as an antibody label in many immunoassays. The feasibility of using non-radioactive iodine as a label was investigated. A microassay for iodide based on the Sandell-Kolthoff reaction was optimised. It was used to detect iodine-labelled antibody and successfully applied to the detection of human IgG in serum samples. The performance of this assay system compared with enzyme-linked immunosorbent assay using HRP was evaluated. PMID- 8354889 TI - Human IgG in immune complexes bound to human erythrocyte CR1 is recognized differently than human IgG bound to an erythrocyte surface antigen. AB - We have developed several methods, including a new use of magnetic cell separation techniques, to examine how human IgG bound to human erythrocytes can be recognized. We find that human IgG in complement-opsonized immune complexes bound to erythrocyte CR1 is less accessible to several probes than human IgG bound to the rhesus antigen on erythrocytes. These findings suggest that the mechanism by which immune complexes are removed and cleared from erythrocyte CR1 in the circulation is different from the mechanisms which lead to splenic clearance of IgG sensitized erythrocytes. PMID- 8354892 TI - Production of monoclonal and polyclonal antibodies against human osteocalcin sequences and development of a two-site ELISA for intact human osteocalcin. AB - In this study we have raised polyclonal and monoclonal antibodies against human osteocalcin sequences coupled to bovine serum albumin (BSA). The antibodies were used for the development of a novel two-site ELISA on microtiter plates for intact human osteocalcin. The epitope, recognized by the monoclonal hybridoma product Os 31/2 that was used as the capture antibody, was located on the amino terminal sequence 1-29. The antibodies used for detection recognized the sequence 1-49. This method failed to detect any tryptic peptides derived from human osteocalcin sequence 1-49 nor did it detect peptide 1-29, thus demonstrating high specificity for the intact osteocalcin 1-49 only. This is a novel technique for the determination of intact osteocalcin. We have also validated the assay parameters for routine use. This direct and relatively simple procedure promises to be a powerful diagnostic and investigative tool. PMID- 8354893 TI - Use of density perturbation to isolate immunologically distinct populations of cells. AB - Experiments have been carried out to demonstrate that, using antibody coated Dynabeads as a model system for density labelling MOLT-4 T cells, the overall density of cells can be increased such that the cells that bind particles can be separated on isopycnic isotonic density gradients from cells that bind fewer particles. The increase in density is dependent on the cell volume and the number of particles bound. After centrifugation, cells with bound particles were found at positions in the gradient that reflected their increased density. Observed density ranges for cells with particular numbers of particles bound coincided closely with calculated expected density ranges. These results indicate the potential for separation of different subpopulations of cells on the basis of the immunological identity of the surface of cells using density perturbation methods involving antibody coated-density particles. PMID- 8354894 TI - A method for the detection of erythrocyte-bound interleukin-8 in humans during interleukin-1 immunotherapy. AB - Interleukin-8 (IL-8) has been recently shown to bind to human erythrocytes with high affinity and is therefore potentially difficult to detect in serum or plasma. IL-8 is transiently elevated in the serum of baboons after the administration of interleukin-1 alpha (IL-1 alpha). The objective of this study was to investigate whether IL-8 can be detected in the plasma or in detergent lysed erythrocytes from cancer patients undergoing treatment with IL-1 alpha. Using a specific radioimmunoassay (RIA), plasma IL-8 was detected within 1-2 h after the first IL-1 alpha infusion. Thereafter, the levels declined rapidly and after 4-8 h were undetectable. Erythrocyte-bound IL-8 was detectable 1-2 h after the increase in plasma levels. The erythrocyte-bound IL-8 levels were higher than those measured in plasma and remained elevated long after the plasma levels had become undetectable. Erythrocyte membranes accounted for all of the erythrocyte associated IL-8, as IL-8 was undetectable in the cytosol after erythrocyte lysis. The assay used in these studies detects IL-8 in erythrocyte lysates when it cannot be measured in plasma and may therefore be useful in monitoring IL-8 production in vivo. PMID- 8354895 TI - Novel method for the measurement of cytokine production by a one-stage procedure. AB - A new one-step culture-immunoassay procedure is described for testing cytokine production by immunocompetent cells in whole blood (WB) without the need for an isolation step. Briefly, WB samples or distilled water were added to RPMI medium containing specific anti-cytokine peroxidase-labelled monoclonal antibodies and incubated in micro-well plates coated with specific capture monoclonal antibodies, directed against distinct epitopes of the cytokine, and containing dried polyclonal activators (5.625 micrograms LPS + 1.125 micrograms PHA) or dried standards respectively. The optimalisation of the assay is described for an extended measurement range. The best compromise between sensitivity and linearity was obtained with the addition of 50 ng/well for TNF-alpha and IL-6 or 100 ng/well for IFN-gamma of unconjugate antibodies to the corresponding conjugate. The kinetics of individual production of each cytokine in WB of normal healthy donors showed values entering the standard range following incubation times of between 2 and 8 h for TNF-alpha, 2 and 4 h for IL-6, and 4 and 24 h for IFN gamma. The sensitivity, the precision (intra-assay CVs) and the reproducibility (interassay CVs) of the assays were as follows: 70 pg/ml, < or = 14% and < or = 11% for TNF-alpha; 25 pg/ml, < or = 11% and < or = 16% for IL-6; 25 pg/ml, < or = 19% and < or = 20% for IFN-gamma. The accuracy (% of recovery) of the assays was in the order of 100% and between 40 and 60% in the absence or presence of polyclonal activators, reflecting the occurrence of an active production/consumption mechanism during the activation. PMID- 8354896 TI - Evaluation of the methodology of polymorphonuclear leukocyte chemotaxis. PMID- 8354897 TI - Background noise in ELISA procedures. Influence of the pH of the coating buffer and correlations with serum IgM concentration. PMID- 8354898 TI - Tuberculosis symposium: emerging problems and promise. AB - Between 1985 and 1991, 39,000 cases of tuberculosis occurred in excess of those expected based on previous trends. Immigration from high-prevalence countries, coinfection with human immunodeficiency virus (HIV), and outbreaks in congregative facilities are most responsible for the increase. Coincident with the increase in tuberculosis, outbreaks of multidrug resistant (MDR) tuberculosis have occurred. Clinical and epidemiologic data support nosocomial transmission. MDR tuberculosis occurred late in the course of HIV infection and was refractory to treatment. Compounding the problems of rising incidence and increasing resistance was the sudden recognition of shortages of antituberculous drugs. The problems currently posed by tuberculosis require new approaches to diagnosis and rapid sensitivity testing as well as assuring an adequate supply of licensed drugs and development of new drugs. A number of steps have been taken by governmental agencies to assure that the challenge is met. PMID- 8354899 TI - Generation of neutralizing anti-B19 parvovirus human monoclonal antibodies from patients infected with human immunodeficiency virus. AB - The prevalence of IgG antibodies to human B19 parvovirus (anti-B19) is elevated in individuals infected with human immunodeficiency virus (HIV), especially during the later stages of HIV infection. In subjects with high titers of IgG anti-B19, 86% (19 of 22) had circulating B cells producing anti-B19. Immortalization of these cells with Epstein-Barr virus and generation of heterohybridomas by fusion with a mouse X human heteromyeloma resulted in the production of two cell lines producing IgG1 kappa monoclonal antibodies (MAbs). Both of these MAbs were specific for conformational epitopes on the VP2 capsid protein of B19 parvovirus and both were capable of neutralizing 50% of the viral infectivity in a human erythroid colony-forming unit assay at < or = 1 micrograms of MAb/mL. These human MAbs are potentially useful in the treatment of acute B19 parvovirus infection. PMID- 8354900 TI - Evidence for mother-to-child transmission of human T lymphotropic virus type II. AB - Serologic analysis of the children of 2 married human T lymphotropic virus type II (HTLV-II)-infected prostitutes demonstrated antibodies to HTLV-II in an 8-year old boy whose only recognizable risk for HTLV-II infection was breast-feeding during his first 4 years of life. Limited sequence analysis of isolates infecting the mother and child demonstrated 100% identical sequences in the long terminal repeat (LTR65-297; 236 bp), pol4762-4919 (157 bp), and env5523-6003 (480 bp) regions (both isolates were subtype a), suggesting mother-to-child transmission. In contrast, isolates obtained from 2 other prostitutes from the same geographic region had sequences different from those of the first woman and her child, and the second and third women were infected with HTLV-II subtype b. Although vertical transmission of HTLV-II in this 8-year-old child cannot be conclusively ascertained, the probability is overwhelming that infection occurred through breast-feeding for an extended period of time. PMID- 8354901 TI - Experimental hepatitis E: pathogenesis in cynomolgus macaques (Macaca fascicularis). AB - The pathogenesis of experimental hepatitis E has not been thoroughly investigated. The purpose of this study was to more accurately document the events in this disease. Cynomolgus macaques were inoculated intravenously with bile or feces containing hepatitis E virus (HEV). Serum, bile, and liver specimens were evaluated with light microscopy, immune electron microscopy, immunofluorescence microscopy, EIA, and polymerase chain reaction. In the third week, there were histopathologic changes and HEV antigen (HEVAg) in liver, HEV in bile, and alanine aminotransferase (ALT) elevations. Widespread pathologic changes were detected during the fourth week and antibody to HEV (anti-HEV) and peak ALT values in the fifth or sixth week. By the sixth week, HEVAg had disappeared but pathologic changes persisted. This study supports the concept that experimental hepatitis E has an initial phase in which hepatic HEV replication is accompanied by the onset of hepatitis and a later phase in which the appearance of anti-HEV is accompanied by progression of the hepatitis. PMID- 8354902 TI - Middle ear abnormalities during natural rhinovirus colds in adults. AB - To determine middle ear pressure (MEP) changes during natural rhinovirus colds, adults with illness for < or = 3 days were tested by digital tympanometer daily for 5 days (study 1) or every other day for 7 days (study 2). Abnormal MEPs (< 50 or > +20 mm H2O) were found in 72% of 36 patients in study 1 (P < .001, vs. baseline of 11%) and 76% of 55 patients in study 2 (P < .001, vs. 15% of 103 healthy controls). Major abnormalities (> or = +100 or < or = -100 mm H2O) were found in 61% of patients in study 1 (P < .001, vs. baseline of 0) and 47% in study 2 (P < .001, vs. control of 5%). MEP abnormalities usually resolved by day 14. Only 1 subject developed clinically apparent otitis media. Earache or respiratory symptom scores did not correlate with MEP abnormalities. These results indicate that natural rhinovirus colds in adults are frequently associated with marked but transient MEP abnormalities. PMID- 8354903 TI - Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B. AB - A recombinant adenovirus (Ad) expressing glycoprotein B (gB) of herpes simplex virus (HSV) type 1 (AdgB8) was evaluated as a mucosal vaccine candidate. When administered intranasally (inl) to C57B1/6 mice, AdgB8 induced levels of serum anti-HSV gB IgG antibodies similar to those of mice immunized intraperitoneally (ip), which neutralized both HSV-1 and -2. Mice immunized inl with AdgB8 produced secretory IgA specific for HSV gB, but mice immunized ip did not. Splenic anti HSV cytotoxic T lymphocytes (CTL) were observed after inl and ip immunization; however, there was a time-dependent decrease in the anti-HSV CTL activity from spleens of inl immunized mice. Anti-HSV CTL were also present in the mediastinal lymph nodes after inl but not ip AdgB8 immunization. Furthermore, mice immunized inl with AdgB8 were protected against heterologous inl challenge with HSV-2, and this protection lasted longer than in ip-immunized mice. These results indicate that mucosal immunization with a recombinant adenovirus can induce mucosal and systemic immune responses and provide long-term protection from mucosally or sexually transmitted viruses. PMID- 8354904 TI - Human peripheral blood xenografts in the SCID mouse: characterization of immunologic reconstitution. AB - Immune reconstitutions (hu-PBL-SCID mice) resulting from adoptive transfer of human peripheral blood mononuclear cells into 1800 C.B-17 scid-/scid-mice were characterized. Over 90% of reconstitutions were successful as evidenced by human immunoglobulin production. Variability was noted with donor, cell number, and cell type. Human cells (T lymphocytes, few B cells) could be recovered by 5 days after engraftment. High levels of soluble CD8 and interleukin-2 receptors were detected in sera of hu-PBL-SCID mice. Cells recovered from 17 mice proliferated in response to antigens to which the donor had been primed; responses to nonboosted antigen also increased in some animals. After reconstitution, lymphocytes were found in the spleen and lymph nodes without full restoration of normal architecture. The hu-PBL-SCID mouse shows promise as a model system for a variety of immunologic studies. The inherent variation in the system must be minimized for appropriate use of the model. PMID- 8354905 TI - Comparative inhibitory effects of various nucleoside and nonnucleoside analogues on replication of influenza virus types A and B in vitro and in ovo. AB - Six nucleoside analogues, two sulfated polysaccharides, and four protease inhibitors were evaluated in vitro as inhibitors of influenza virus replication. Four guanosine analogues (mizoribine, ribavirin, pyrazofurin, and 5-ethynyl-1 beta-D-ribofuranosylimidazole-4-carboxamide), the sulfated polysaccharide dextran sulfate (molecular weight 500,000), and two protease inhibitors (camostat mesilate and nafamostat mesilate) were inhibitory to the replication of strains of influenza virus types A and B at concentrations down to 0.3 micrograms/mL. Of these seven compounds, ribavirin, camostat mesilate, and nafamostat mesilate were efficacious in both reducing the virus titer and increasing the survival rate of influenza virus-infected chick embryos. For camostat mesilate, the ED50 (required to improve the survival rate of influenza virus-infected chick embryos by 50%) was 0.80 micrograms/g, and its selectivity index, based on the ratio of the 50% toxic dose (required to reduce the viability of chick embryos by 50%) to ED50, was 280. Camostat mesilate deserves further exploration for its potential in the treatment of influenza virus infection. PMID- 8354906 TI - Maternal immunization with influenza or tetanus toxoid vaccine for passive antibody protection in young infants. AB - Women in the last trimester of pregnancy were given trivalent inactivated influenza virus vaccine (TIV; A/Sichuan/H3N2, A/Taiwan/H1N1, B/Victoria) or tetanus toxoid (TT). Maternal blood was drawn before immunization and at delivery (median, 5 weeks later); infant blood was obtained within 5 days of birth and 2 months later. Antibody responses to TIV and TT were determined by microneutralization assay and ELISA. T cell response was determined by lymphocyte proliferation. Maternal seroconversion to vaccine antigens was found to one or more influenza antigen in all TIV recipients and to TT in 9 of 13 TT recipients. Significantly higher IgG antibodies to maternal vaccine antigens were present in cord and infant serum. Significant blastogenic responses were seen to influenza A and B in maternal cells of TIV-immunized women but not in cord or infant lymphocytes. Maternal immunization resulted in higher infant levels of vaccine specific IgG antibody but not in the transfer of specific T lymphocyte response(s) or production of neonatal IgM antibody. PMID- 8354907 TI - Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis. AB - In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria. PMID- 8354908 TI - Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines. AB - The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease. PMID- 8354909 TI - Triple combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a highly penicillin-and glycopeptide-resistant isolate of Enterococcus faecium. AB - A combination of low-dose penicillin (75,000 IU/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IU/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to beta-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 micrograms/mL) and vancomycin (MIC, 512 micrograms/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killing-curve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination. PMID- 8354910 TI - Norway rats as reservoir hosts for Lyme disease spirochetes on Monhegan Island, Maine. AB - To determine whether the agent of Lyme disease, Borrelia burgdorferi, may be maintained in the absence of its usual white-footed mouse reservoir host, Ixodes dammini ticks from an island where mice are absent were examined. Prevalence of spirochetal infection was described for ticks removed from mammals, birds, and vegetation on Monhegan Island, Maine. Forty percent of adult I. dammini removed from vegetation were infected. Norway rats were heavily infested with ticks, and > 60% of such ticks contained spirochetes. Other hosts were less frequently infested by ticks, and few such ticks were infected by spirochetes. The prevalence of antibody to B. burgdorferi was 23% in dogs and cats; 4% of island residents had Lyme disease. Thus, rats maintain Lyme disease spirochetes on Monhegan Island, and there may be transmission of this agent by I. dammini to island residents and their pets. PMID- 8354911 TI - Combination therapy in experimental invasive aspergillosis. AB - Combination antifungal therapy was assessed in an immunosuppressed rabbit model of invasive aspergillosis. Treatment with fluconazole, amphotericin B, or a combination of both significantly prolonged survival of animals lethally challenged with Aspergillus fumigatus. High-dose amphotericin B was the most effective therapy for invasive aspergillosis. Although no antagonism was seen when fluconazole was given prophylactically or therapeutically in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B. Animals given a sublethal challenge of A. fumigatus had lower mortality rates when given amphotericin B, fluconazole as treatment or prophylaxis, or various combination therapies. Only animals treated with flucytosine had mortality rates comparable to those of controls. No antagonism was observed with combinations of fluconazole and amphotericin B, flucytosine and amphotericin B, or fluconazole and flucytosine. These observations provide evidence that fluconazole, flucytosine, and amphotericin B used in various combinations are not antagonistic and may provide some insight into the treatment of invasive aspergillosis in humans. PMID- 8354912 TI - Epidemiology of cutaneous leishmaniasis in Colombia: a longitudinal study of the natural history, prevalence, and incidence of infection and clinical manifestations. AB - This prospective study measured the incidence of Leishmania infection, by Leishmanin skin test (LST) conversion, and leishmaniasis, by new acquisition of lesions, in a Leishmania braziliensis endemic area of Colombia, during 7243 person-years. The incidence rate of infection and leishmaniasis varied greatly by village, ranging from 2.8 to 23.0/100 person-years and 0.0 to 20.4/1000 person years, respectively. Adult males experienced greater rates of both infection and leishmaniasis. Most primary infections (91%) were subclinical initially. Typical scars were predictive of subsequent leishmaniases both for persons initially LST reactive (risk ratio = 11.3, P = .003) and for those initially nonreactive (risk ratio = 3.2, P = .02). Only one-third of the diagnosed leishmaniasis cases (24/77) were due to newly acquired infections in naive hosts. The relative contribution of existing lesions, recurrences, and new infections to the burden of disease should be considered in the planning of leishmaniasis control programs. PMID- 8354913 TI - Epidemiology of cutaneous leishmaniasis in Colombia: environmental and behavioral risk factors for infection, clinical manifestations, and pathogenicity. AB - Through a longitudinal, active surveillance for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis infection and lesions on the Pacific Coast of Colombia, risk factors for infection (leishmanin skin test conversion), leishmanial lesions, and pathogenicity were examined. Risk factor information was obtained prior to and independently of case ascertainment. Similar factors were associated with acquisition of infection and of leishmaniasis, including male sex, age > 10 years, and farming occupation. The behaviors of entering the forest after sunset, hunting, and lumbering were most strongly associated with Leishmania infection independently of age, sex, and farming occupation. Environmental conditions associated with infection, including tall trees near the home, home located > 15 m from the nearest neighbor, and floor and roof made of open material, were less strong predictors of risk. Pathogenicity, the risk of lesion given a new infection, was reduced in those > 30 years of age and those entering the forest frequently. PMID- 8354914 TI - Direct detection of infectious human immunodeficiency virus type 1 (HIV-1) immune complexes in the sera of HIV-1-infected persons. AB - The sera of human immunodeficiency virus type 1 (HIV-1)-infected subjects were examined for the presence of infectious HIV-1-antibody complexes by their ability to infect Fc gamma receptor (Fc gamma R)-bearing cells. Infection of Fc gamma R bearing cells by a serum in which half of the p24 antigen was present in a form of immune complexes was inhibited by aggregated human immunoglobulin. Then in studies on 22 sera, 9 sera produced p24 antigen during 14 days of culture in U937 cells. HIV-1 p24 production was inhibited or delayed by the pretreatment of cells with aggregated human immunoglobulin in 6 of the 9 sera that were infectious. These results may reflect interactions between virus-antibody complexes and Fc gamma R-bearing cells in vivo because serum itself was used as the source of virus and virus-antibody complexes. The results indicate that infectious HIV-1 immune complexes are present in the circulation of HIV-1-infected patients. PMID- 8354915 TI - Endemic human T cell leukemia virus type II infection in southwestern US Indians involves two prototype variants of virus. AB - Human T cell leukemia virus (HTLV) type II is endemic in certain American Indians, and high rates of infection occur in intravenous drug users (IVDUs). North American IVDUs are infected with two distinct variants, HTLV-IIa and -IIb. If IVDUs became infected as a result of interaction with members of an American Indian population, both viral forms should be demonstrable in such populations. Nucleotide sequence analysis of 630 bases of the env gene encoding the gp21 protein was done on DNA from 12 New Mexico Indians (8 Pueblo, 4 Navajo). All samples were typical subtype a or b viruses. Seven of the 8 Pueblo and 2 of 4 Navajo had subtype b; the rest had subtype a. The results are compatible with an indigenous New World origin for both subtypes of HTLV-II. PMID- 8354916 TI - Campylobacter immunity and quantitative excretion rates in Thai children. AB - Campylobacter species were isolated from 61 (15%) of 416 Thai children < 5 years old with diarrhea. Although the baseline levels of Campylobacter-specific antibody increased with age, 80.3% of Campylobacter-infected children seroconverted compared with 12.9% of 45 Shigella-infected patients used as controls. The response to acute infection was greatest in the 6- to 12-month-old group. Nonseroconverters had higher initial IgG levels than did seroconverters (P = .001). Quantitative cultures showed a range of 1-8 log10 Campylobacter cfu/g of stool (median, 6.0 log10), and the seroconversion rate was highest in those with the highest Campylobacter excretion. Fecal Campylobacter excretion was inversely related to age (chi 2 for trend, P = .03). These studies indicate that endemic Campylobacter exposure frequently induces seroconversion in young children, whether Campylobacter is isolated as a single pathogen or one of multiple pathogens, and that fecal excretion of the organism is inversely related to the age-related immune response to infection. PMID- 8354917 TI - Capsular types of Vibrio vulnificus: an analysis of strains from clinical and environmental sources. AB - Vibrio vulnificus produces a capsular polysaccharide (CPS) that is essential for virulence. CPS from V. vulnificus clinical strain MO6-24 has been purified and the structure determined. In preliminary screening with antisera raised to MO6-24 CPS, 4 (19%) of 21 clinical isolates (including MO6-24), but none of 67 environmental V. vulnificus isolates, agglutinated with anti-MO6-24 antisera (P = .003). CPS was isolated from a subset of 12 clinical and 7 environmental isolates and analyzed by high-performance anion-exchange chromatography and one dimensional nuclear magnetic resonance. MO6-24 and 1 other serologically positive strain had identical CPS structures; the other 2 serologically positive strains had substitutions in two of four sugar residues. Thirteen other capsular types were identified among the remaining 15 strains from which CPS was extracted. PMID- 8354918 TI - Kinetics of specific IgG antibodies for monitoring the effect of anti Helicobacter pylori chemotherapy. AB - A total of 104 patients with recurrent duodenal ulcer were treated with either ranitidine plus amoxicillin plus metronidazole or ranitidine plus placebo. To study the effect of the eradication of Helicobacter pylori on the systemic immune response in an IgG ELISA, sera were drawn from all patients before the onset of therapy and at 6, 16 +/- 2, 32 +/- 2, and 60 +/- 2 weeks after therapy. In patients with eradication of the organism, a significant (P < .001) reduction of the specific IgG titer occurred. This was not observed in patients without bacterial eradication. If a titer reduction of > 50% was taken as an indicator for eradication of H. pylori, the sensitivity of the serologic test was 97.6% 99.7%. Its specificity increased with the interval to the onset of chemotherapy from 56.3% to 97.6%. Serologic tests are simple to perform and cause very little discomfort to the patient. PMID- 8354919 TI - Salicylate potentiates amikacin therapy in rodent models of Klebsiella pneumoniae infection. AB - In vitro effects of salicylate on Klebsiella pneumoniae include capsule repression and enhanced aminoglycoside activity. The effects of high-dose salicylate on amikacin therapy were assessed in animal models. In a mouse lethality model, amikacin protective doses were reduced up to 12-fold by salicylate doses of 277 mg/kg. Salicylate alone increased the LD50 for K. pneumoniae in mice by nearly 1 log unit. In a lobar pneumonia model, rats received salicylate-amikacin intravenously 3 days after challenge, and bacteria were quantified from lung tissue on day 7. Rats receiving one-fourth the minimum effective amikacin dose had 1 x 10(6) cfu/g of lung, while no bacteria were detected in those also receiving salicylate (173 mg/kg). At one-eighth the minimum effective dose of amikacin, salicylate prevented the development of pneumonia. Salicylate potentiation of antimicrobial therapy far surpassed that observed in vitro, yet the potentiation was abolished in neutropenic animals. Thus, salicylate may enhance phagocytosis rather than antibiotic action in therapy. PMID- 8354920 TI - Use of polymerase chain reaction in an epidemiologic investigation of Pontiac fever. AB - In June 1992, 13 (38%) of 34 resort guests experienced illness that met a symptom based case definition of Pontiac fever. Each ill guest reported using an indoor hot tub compared with 6 (29%) of 21 nonill guests (P < .001). Water samples from the indoor hot tub were culture-negative for legionellae using standard techniques, coculture with amebae, and intraperitoneal inoculation of guinea pigs. However, polymerase chain reaction (PCR) testing of the water samples indicated the presence of Legionella pneumophila. Direct fluorescent antibody testing identified the organism as serogroup 6. Seroconversion to L. pneumophila serogroup 6 occurred in 7 (64%) of 11 ill guests and none of 5 nonill guests (P = .03). These results suggest that in certain circumstances, culture of environmental samples should be supplemented with additional tests such as PCR. These results are also consistent with the concept that Pontiac fever can be caused by nonviable legionellae. PMID- 8354921 TI - Prospective evaluation of red man syndrome in patients receiving vancomycin. AB - The incidence of red man syndrome (RMS) and its relationship to histamine were investigated in patients receiving vancomycin or an aminoglycoside (control). During the 60-min infusions, patients were observed for signs or symptoms consistent with RMS, including pruritus, erythema, angioedema, and cardiovascular depression. Four blood samples were obtained at 30-min intervals for determination of histamine concentrations. One (3.4%) of 29 vancomycin- and none of 8 aminoglycoside-treated patients had documented RMS. The mean maximum changes in blood pressure and heart rate were not significant and were similar between groups. Increases in histamine concentrations to > 1 ng/mL occurred only in 25% (2/8) of the aminoglycoside patients. Vancomycin induced minimal changes in histamine concentrations despite the occurrence of RMS. From these observations, it appears that RMS is not closely associated with histamine release, and elevated histamine concentrations do not predict RMS. Further investigation is needed to elucidate other mediators of RMS. PMID- 8354922 TI - Isolation of Mycobacterium avium complex from bone marrow aspirates of AIDS patients in Brazil. AB - Mycobacterium avium complex (MAC) infection has not been reported as a major opportunistic infection among patients with AIDS in Latin America or Africa. In this study, 125 AIDS patients who had persistent fever, anemia, and leukopenia were examined among 2628 AIDS patients admitted to Instituto de Infectologia Emilio Ribas between May 1990 and April 1992. From the bone marrow aspirates of the 125 patients, MAC was isolated from 23 (18.4%) and Mycobacterium tuberculosis was isolated from 9 (7.2%). Between 1985 and 1990, only 11 MAC isolations among 60,000 cultures obtained from human immunodeficiency virus-seronegative patients were documented in Sao Paulo. Hence, the minimal estimated rate of MAC infection in AIDS patients in this city was 23/2628, or 0.88%. These findings suggest that MAC infection is an important opportunistic infection, especially among a subset of patients with AIDS in Brazil who have clinical characteristics and risk activities similar to those associated with MAC infections in North America and Europe. PMID- 8354923 TI - Polymerase chain reaction for the diagnosis of candidemia. AB - A PCR assay was developed for the diagnosis of candidemia. Primers were selected to amplify a 158-bp segment from the Candida actin gene that was detected by hybridization with a 32P-labeled oligomer probe. The lower limit of detection was DNA extracted from 10 Candida yeasts/sample, or 25 fg of purified Candida albicans DNA. This PCR was specific for medically important Candida species. Circulating Candida DNA was detected by this PCR from plasma of mice with induced candidemia and from sera in 11 (79%) of 14 patients with blood cultures positive for Candida species. This PCR may offer a sensitive method for diagnosis of candidemia. PMID- 8354924 TI - Serum IgG reactivity with 41-, 31-, and 28-kDa larval proteins of Strongyloides stercoralis in individuals with strongyloidiasis. AB - Proteins from a deoxycholate-soluble extract of Strongyloides stercoralis infective larvae were separated by SDS-PAGE, blotted onto nitrocellulose paper, and reacted with sera from individuals with confirmed S. stercoralis infections (n = 100), suspected S. stercoralis infections in whom no larvae could be detected (n = 27), and other nematode infections (40 with Wuchereria bancrofti, 20 with Onchocerca volvulus, 20 with Necator americanus, and 20 with mixed Ascaris lumbricoides and Trichuris trichiura infections). Immunodominant proteins of approximately 41, 31, and 28 kDa were recognized by IgG in 91%, 88%, and 90%, respectively, of sera from those with confirmed strongyloidiasis; in 100%, 100%, and 93% of sera from those with suspected strongyloidiasis; and in 9%, 12%, and 14% of sera from those infected with other nematodes. IgG reactivity to each of these proteins was a more specific means of immunodiagnosis than the currently used indirect ELISA; the methods were equally sensitive. PMID- 8354925 TI - Treponemal infection and outcome of pregnancy. PMID- 8354926 TI - Interferon-alpha therapy for patients with chronic fatigue syndrome. PMID- 8354927 TI - Evidence of direct transmission of Escherichia coli O157:H7 infection between calves and a human. PMID- 8354928 TI - Liposome-encapsulated ciprofloxacin is effective in the protection and treatment of BALB/c mice against Francisella tularensis. PMID- 8354929 TI - The value of the second blood culture. PMID- 8354930 TI - Tampon-collected genital cells in the detection of Chlamydia trachomatis by polymerase chain reaction. PMID- 8354931 TI - Rapid detection of acute cholera in airline passengers by coagglutination assay. PMID- 8354932 TI - Determination of Mycobacterium leprae viability by polymerase chain reaction amplification of 71-kDa heat-shock protein mRNA. PMID- 8354933 TI - Soluble interleukin-2 receptor is involved during systemic mycosis. PMID- 8354934 TI - [Structure and functions of vacuolar-type H(+)-ATPase from animal cells]. PMID- 8354936 TI - [Catenins: the proteins associated with the cytoplasmic domain of cadherins]. PMID- 8354935 TI - [Biosynthesis, processing and activity control of cathepsin E]. PMID- 8354937 TI - [Phosphorylation in tau protein]. PMID- 8354938 TI - [Fractionation of capillary HPLC peaks for protein sequencing]. PMID- 8354939 TI - Pursuing an elusive goal: molding strategic teachers and learners. PMID- 8354940 TI - Integrative strategy instruction: a potential model for teaching content area subjects to adolescents with learning disabilities. AB - In part because learning strategies are often taught in isolated resource settings outside of the contexts in which students with learning disabilities are expected to apply this knowledge, generalization has been a significant challenge to educators. To address this problem, an instructional model is proposed for integrating cognitive strategy instruction and content area instruction when teaching students in content area classes. Teacher-directed instructional procedures, cooperative learning, and direct explanation and dialectical strategy instruction are integrated into four key instructional processes: orienting, framing, applying, and extending. In this model, teacher-mediated instructional devices and routines used to teach content area subjects serve as a basis for teaching students to self-mediate parallel cognitive strategies and processes. The model is discussed in terms of its theoretical and philosophical orientations as manifested in its knowledge and instructional bases. A scenario is provided that depicts a social studies teacher implementing many of the principles and methods associated with the model. PMID- 8354941 TI - Devices and desires: integrative strategy instruction from a motivational perspective. PMID- 8354942 TI - Special education for the twenty-first century: integrating learning strategies and thinking skills. PMID- 8354943 TI - Ellis's "potential" integrative strategy instruction model: an appealing extension of previous efforts. PMID- 8354944 TI - A four-year longitudinal investigation of the social skills and behavior problems of students with learning disabilities. AB - This longitudinal, prospective study investigated the social skills and behavior problems of three groups of students (10 students per group) from kindergarten through third grade: learning disabilities (LD), low achievement (LA), and average/high achievement (A/HA). Social skills and behavior problem rating scales were completed by teachers on all students during kindergarten through third grade. Students in the LD and LA group exhibited significantly lower social skills and higher levels of behavior problems than their A/HA peers, but no significant differences for either measure were found between the LD and LA groups. Scores on the cooperating/responding factor of the social skills rating scale increased over time, but scores on the outgoing/initiating factor of the social skills rating scale did not change significantly over time. Discussion focused on the finding that students in the LD and LA groups did not differ significantly on social skills or behavior problems over time, though both groups demonstrated more behavior problems and lower social skills than the A/HA students. PMID- 8354945 TI - Referral-to-placement ratio: a finding in need of reassessment? AB - Previous research has reported that the number of evaluated children placed in special education is as high as three out of four. The purpose of the present study is to reassess, extend, and update referral-to-placement research. Subjects consisted of 236 predominantly white children referred for special education evaluation from 12 suburban and rural school districts. Of the 236 pupils referred, 128 were diagnosed as learning disabled (LD) by a multidisciplinary team (MDT). The 128 students identified as eligible for services for students with LD had a mean IQ of 96.43 and a mean age of 10.2. The majority of the subjects were male (70%). The results suggest that the number of students referred who are actually placed is lower (approximately one out of two) than previously reported. It is concluded that further research is needed to verify the current referral-to-placement ratio and to explore the factors influencing this ratio. PMID- 8354946 TI - The relationship between learning disabilities and persisting delinquency. AB - Recidivism of delinquency in juveniles with learning disabilities (LD), the focus of the present study, has been virtually unexplored in previous research. Data from a longitudinal study initiated in 1978 are examined. Sixty-five subjects with LD (47 males and 18 females) who had been diagnosed and assessed between the ages of 8 and 12 years were located and, during a personal structured interview at the median age of 18 years, reported police contact. This population was subdivided into two groups on the basis of whether police contact had continued or discontinued, as reported in a second personal interview at the age of 25 years. Discriminant analysis on parent and subject variables correctly classified 75% of the subjects and revealed that certain personality characteristics, such as impulsivity and poor judgment, discriminate between persisting and nonpersisting delinquency in youth with learning disabilities. PMID- 8354947 TI - Effect of aging on cholesterol 7 alpha-hydroxylation in humans. AB - In order to investigate the alterations of bile acid synthesis in aging, we studied the rates of cholesterol 7 alpha-hydroxylation, the rate-limiting step, in 28 patients of different ages (34-83 years old, 14 below and 14 above the age of 65) of both sexes. Hydroxylation rates were determined by tritium release assay after an intravenous bolus of [7 alpha-3H]cholesterol. Cholesterol 7 alpha hydroxylation was significantly decreased in the older age group, compared to middle-aged subjects, both in males and females; moreover, a significant inverse correlation between hydroxylation rates and age was found in the whole sample (r = -0.56; P < 0.01) and in females, but not in males. The percent concentration of deoxycholic acid in plasma (determined by gas-liquid chromatography) was increased in older subjects. Plasma cholesterol and triglyceride levels were not related with age even though triglyceride concentrations tended to be lower in the older age group. Triglyceride, but not cholesterol levels, were directly correlated with hydroxylation rates (r = 0.45, P < 0.05). After cholestyramine treatment (8-12 g/day for 4 weeks) a sharp increase in 7 alpha-hydroxylation rates was observed in three elderly patients, accompanied by reduced levels of dihydroxylated bile acids. Our data are consistent with a reduced rate of conversion of cholesterol to bile acids with aging, particularly in females, and suggest a coordinate reduction of triglyceride production. Alterations of the quantitative and/or qualitative pattern of the bile acid pool recirculating to the liver may be responsible, at least in part, for the changes observed. PMID- 8354948 TI - Analysis of plasma lipids by NMR spectroscopy: application to modifications induced by malignant tumors. AB - Lipid extracts of plasma were studied by 31P and 1H NMR spectroscopy at 9.4 T. Signals recorded on lipid mixtures were assigned to different lipid classes using a data base built with two-dimensional 1H COSY spectra of seven standard lipids. Signals unique to glycerophospholipids, sphingolipids, and triacylglycerols were identified. 31P and 1H NMR spectroscopy was used to study qualitative and quantitative modifications induced in plasma by malignant tumors. The results show a significant increase in triglyceride/phospholipid ratio and a concomitant decrease of total phospholipids in patients with cancer. In order to check for the possible presence of particular lipids such as glycolipids in these patients, 1H COSY spectra were recorded on the intact plasma and on extracts of plasma lipids in patients with cancer and in healthy subjects. Only in one case of ovarian cancer, a cross-peak at 1.35 and 4.15 ppm, corresponding to fucose residue in glycolipids, was detected. PMID- 8354949 TI - Analysis of techniques to obtain plasma for measurement of levels of free fatty acids. AB - Accuracy in measurement of plasma free fatty acids (FFA), and therefore prevention of the in vitro lipolysis, is a crucial step to understand the physiologic role of plasma FFA and their relationships in the pathogenesis of important metabolic disorders such as central obesity, insulin resistance, and diabetes mellitus. As lipoprotein triglyceride-fatty acids are elevated in these states, in vitro lipolysis of triglycerides may artifactually increase FFA. Plasma FFA were measured in subjects before and after heparin administration, under different experimental conditions affecting the in vitro activity of lipoprotein lipase (LPL) and hepatic lipase (HL). Paraoxon, a cholinesterase inhibitor neurotoxin known to block plasma lipolytic activity, and preextraction timing and temperature of collection were tested. Paraoxon was required to prevent triglyceride hydrolysis in: a) preheparin plasma allowed to stand at room temperature (21 degrees C) for 2 h, before being frozen at -20 degrees C (FFA = 1817 +/- 291 vs. 698 +/- 66 microEq/l, P < 0.005, mean +/- SEM, without and with paraoxon, respectively); and b) in postheparin plasma immediately stored at -20 degrees C (FFA = 2682 +/- 357 vs. 1299 +/- 150 microEq/l, P < 0.005, without and with paraoxon, respectively). No difference in the FFA level was found in preheparin plasma collected either with or without paraoxon when: a) the samples were placed in ice and immediately assayed; b) the specimens were immediately frozen at -70 degrees C and assayed 60 days later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354950 TI - Quantitation of plasma lipids by gas-liquid chromatography on high temperature polarizable capillary columns. AB - We have previously demonstrated the potential usefulness of capillary columns coated with a high temperature polarizable phenylmethylsilicone liquid phase in plasma lipid profiling (Kuksis, A., J.J. Myher, and P. Sandra. 1990. J. Chromatogr. 500: 427-441). The present study reports improved operating conditions along with a practical application to the analysis of a series of human plasma samples in comparison to capillary gas-liquid chromatography on nonpolar columns. For this purpose the plasma lipids were dephosphorylated with phospholipase C and converted to the trimethylsilyl ethers. The molecular species of the plasma lipids were identified by comparing the relative retention times to reference standards. The species were quantitated using tridecanoylglycerol as internal standard. The recoveries of the lipid classes were determined by summing the molecular species within each carbon number and comparing the proportion of the carbon numbers obtained on polar and nonpolar columns. The relative recoveries varied with the lipid class and sample load and averaged as follows: FA C16, 78%; FA C18, 78%; FC, 99%; tridecanoylglycerol (TD), 100% (by definition); CER 34:1, 92%; DG C34, 103%; DG C36, 98%; CE C16, 73%; CE C18, 61%; TG C50, 93%; TG C52, 60%; TGC54, 32%. We conclude that high temperature polarizable capillary columns are suitable for qualitative and quantitative assessment of plasma lipids and provide more information per man-hour, instrument time, and unit cost than any other analytical method known. PMID- 8354951 TI - Evaluation of deuterated cholesterol and deuterated sitostanol for measurement of cholesterol absorption in humans. AB - The continuous isotope feeding method of Crouse and Grundy (1978. J. Lipid Res. 19: 967-971) for measurement of dietary cholesterol absorption has been modified by using markers labeled with stable isotopes ([2,2,4,4,6-2H5]cholesterol or [25,26,26,26,27,27,27-2H4]cholesterol or [26,26,26,27,27,27-2H6] cholesterol and [5,6,22,23-2H4]sitostanol) quantified by gas-liquid chromatography-selected ion monitoring. Tracing of the isotope distribution of the authentic markers and after their intestinal passage, including the microbiological products (coprostanol and coprostanone) revealed stability of the labels. The new method was evaluated in six monkeys on two occasions by comparison with the original method using radioactively labeled cholesterol and sitosterol. The results obtained by the two different methods were in excellent agreement, and absorption ranged from 49% to 73% (mean 60%) for the stable isotope method and from 51% to 69% (mean 62%) for the radioactive method. The coefficient of variation of cholesterol absorption in animals ranged from 3.9% to 15.1% (mean 7.1%) for stable isotopes and 1.9% to 13.6% (mean 5.7%) for radioactive isotopes. In twelve subjects cholesterol absorption was measured by the new method from total fecal samples frozen immediately and compared to results obtained from small fecal aliquots (approximately 1 g) sent by ordinary mail to the laboratory. A significant correlation of cholesterol absorption between the two different sample handlings was obtained (r = 0.981, P < 0.001). In addition, measurement of cholesterol absorption twice in seven volunteers 2 weeks apart revealed identical results. Thus, the new method is extremely safe and reproducible without radioactive exposure to the subjects and labortory staff and can be used on women of child-bearing age. PMID- 8354952 TI - Assessment of percent cholesterol absorption in humans with stable isotopes. AB - Dietary cholesterol restriction is a general recommendation for the medical community and emphasizes the importance of intestinal cholesterol absorption and metabolism in humans. However, several methods that may accurately quantify cholesterol absorption utilize radioactive isotopes that are undesirable for younger individuals, women, children, and normal subjects. To eliminate this hazard, we have developed a procedure for measurement of percent cholesterol absorption, based on that of Zilversmit (1972. Proc. Soc. Exp. Med. Biol. 140: 862-865), using stable nonradioactive isotopic tracers of cholesterol. [26,26,26,27,27,27-2H]cholesterol (30 mg) was administered orally and [23,24,25,26,27-13C]cholesterol (15 mg) was administered intravenously on day 0 and percent cholesterol absorption was calculated as the plasma ratio of oral/intravenous isotopic tracer on day 3 as determined by gas chromatography mass spectrometry with selected ion monitoring. Tracer cholesterol given orally peaked in plasma on day 2 and then slowly declined in parallel with the intravenous tracer. Cholesterol absorption in 16 healthy subjects (on no medication and not ingesting alcohol) consuming a Step One Diet was 53.5% +/- 8.5 SD%. Five subjects underwent repeat testing after 4-6 weeks with excellent replication (SD of difference between tests = 2.8%). No differences in the metabolism of [13C5]cholesterol, [2H6]cholesterol, and [14C]cholesterol were observed. The use of stable isotopes for the study of percent cholesterol absorption is precise and safe, allowing repeated measurements in normal individuals and thus facilitating clinical investigation of this key component of human cholesterol metabolism. PMID- 8354953 TI - Hypertriglyceridemia in nephrotic rats is due to a clearance defect of plasma triglyceride: overproduction of triglyceride-rich lipoprotein is not an obligatory factor. AB - This study was conducted to determine whether overproduction of triglyceride-rich lipoprotein is an obligatory factor for experimental hypertriglyceridemia in nephrotic rats. Nephrosis was induced in male Wistar rats by administration of 150 mg/kg puromycin aminonucleoside. Nephrotic rats had slightly increased triglyceride secretion rate (TGSR) estimated using Triton WR1339 (0.53 +/- 0.05 vs. 0.45 +/- 0.04 mg/min, P < 0.05 vs. control rats) and marked hypertriglyceridemia (330.4 +/- 78.6 mg/dl). Rats made diabetic by 40 mg/kg streptozotocin were normotriglyceridemic (66.3 +/- 12.1 mg/dl) but had suppressed TGSR (0.33 +/- 0.09 mg/min). Experimental nephrosis was induced in diabetic rats. Their TGSR remained suppressed (0.35 +/- 0.06 mg/min) but they had marked hypertriglyceridemia (296.6 +/- 72.4 mg/dl) suggesting further impairment of triglyceride removal from the circulation in diabetic rats caused by nephrosis. Endogenously radiolabeled very low density lipoprotein (VLDL)-triglyceride from donor rats was reinjected into normal recipient rats. [3H]VLDL from the experimental groups (the rats with nephrosis, diabetes with nephrosis, and diabetes alone) were more slowly cleared by normal rats than VLDL from normal rats. These results suggest that circulating insulin is essential for increased triglyceride secretion in experimental nephrosis and that nephrotic hypertriglyceridemia can be induced only by a triglyceride removal defect. Therefore, hypersecretion of triglyceride-rich lipoprotein is not an obligatory factor for nephrotic hypertriglyceridemia. PMID- 8354955 TI - Genetic variation in mouse apolipoprotein A-IV expression is determined pre- and post-transcriptionally. AB - Among inbred mouse strains there is a striking genetic variation in the levels of apolipoprotein A-IV (apoA-IV) mRNA in the liver, although intestinal mRNA levels vary only twofold in these strains. In the present study we have characterized the apoA-IV expression phenotypes in strains C57BL/6J and 129/J, and investigated the molecular basis for the genetic variation. We report that the two strains differ eight- to tenfold both in the levels of apoA-IV mRNA and in the rate of apoA-IV protein synthesis in liver. Presumably due to the increased synthetic rate, strain 129 exhibits a threefold higher concentration of apoA-IV protein in the circulation. mRNA synthesis and turnover studies indicate that both transcriptional and post-transcriptional events contribute to the genetic variation in steady state apoA-IV mRNA levels. An analysis of the levels of apoA IV mRNA derived from 129 and C57BL/6 alleles in F1 mice indicates that the genetic control of apoA-IV mRNA levels involves both cis-acting elements linked to the apoA-IV gene, and genetically distinct trans-acting factors. PMID- 8354956 TI - Effect of membrane lipids on the lactosylceramide molecular species specificity of CMP-N-acetylneuraminate:lactosylceramide sialyltransferase. AB - It has previously been shown that when the molecular species specificity of rat liver Golgi CMP-N-acetylneuraminate:lactosylceramide alpha 2,3-sialyltransferase was determined, using as the substrate lactosylceramide (LacCer) incorporated into liposomes prepared with rat liver Golgi lipids, the enzyme showed a pronounced variation in activity towards the various molecular species of LacCer (J. Lipid Res. 1989. 30: 1789-1797). In this paper, -the LacCer molecular species specificity of sialyltransferase from neuroblastoma NB2a cells was examined using five naturally occurring and three synthetic molecular species of LacCer. The enzyme activity was determined by following the formation of [14C]GM3 from CMP [14C]neuraminic acid and individual molecular species of LacCer incorporated into liposomes. Nonspecific lipid transfer protein was included in the enzyme assay to facilitate the transfer of LacCer and other lipids between the liposomes and the membrane where sialyltransferase is located. In these enzyme assays the liposomes contained approximately 10 times more lipid phosphorus than either the microsomal fraction of NB2a cells or the Golgi fraction of rat liver. Thus, in the presence of nonspecific lipid transfer protein, the lipid composition of the membrane where sialyltransferase is located was modified to resemble the lipid composition of the liposomes. When the molecular species specificity of NB2a cell sialyltransferase was determined with LacCer incorporated into liposomes prepared with NB2a cell lipids, the enzyme showed no specificity towards the various molecular species of LacCer. However, when the molecular species specificity of NB2a cell sialyltransferase was determined with LacCer incorporated into liposomes prepared with rat liver Golgi lipids, the enzyme showed a variation in activity towards the various LacCer molecular species similar to that observed with the liver Golgi enzyme using liposomes prepared with liver Golgi lipids. Likewise, when the molecular species specificity of rat liver Golgi sialyltransferase was determined with LacCer incorporated into liposomes prepared with NB2a cell lipids, the liver enzyme then showed no specificity towards the various molecular species of LacCer. These results indicate that the lipid environment of the membrane can alter the molecular species specificity of sialyltransferase towards its lipid substrate, LacCer. PMID- 8354954 TI - Cholesterol 7 alpha-hydroxylase: evidence for transcriptional regulation by cholesterol or metabolic products of cholesterol in the rat. AB - Cholesterol 7 alpha-hydroxylase, the rate-determining enzyme in the bile acid biosynthesis pathway, is regulated in a negative feedback manner by hydrophobic bile salts returning to the liver via the portal circulation. The role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase and the interrelationship between the cholesterol and bile acid biosynthesis pathways remain controversial. The objective of the present study was to define the role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase and determine the molecular level of its control. In order to avoid intestinal or intravenous administration of cholesterol, we manipulated the flow of cholesterol within the hepatocytes by decreasing cholesterol synthesis with lovastatin in bile fistula rats (bile acid synthesis is up-regulated), or by increasing cholesterol supply by administering mevalonate, a precursor of cholesterol, to rats with intact enterohepatic circulation (bile acid synthesis is normal). In the first series of studies, lovastatin was administered as a single intravenous bolus (10 mg/kg) to rats with chronic bile fistula and to rats with intact enterohepatic circulation (cholesterol and bile acid synthesis is normal). Three hours after lovastatin administration, cholesterol 7 alpha-hydroxylase specific activity, enzyme mass, mRNA, and gene transcriptional activity were decreased by 35%, 32%, 56%, and 34%, respectively, in rats with chronic bile fistula. In rats with intact enterohepatic circulation, lovastatin administration resulted in a similar decrease (34%) of cholesterol 7 alpha-hydroxylase specific activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354957 TI - Metabolism and choleretic activity of homochenodeoxycholic acid in the hamster. AB - The hepatic metabolism and the choleretic effect of homochenodeoxycholic acid, the C25 homologue of chenodeoxycholic acid, were investigated in the hamster. After intravenous administration of 3H-labeled homochenodeoxycholic acid into biliary fistula hamsters, more than 80% of the radioactivity was recovered in bile in 4 h. A relatively small proportion of homochenodeoxycholic acid was present in bile as the taurine (22%) or glycine (4%) conjugate. However, more than 70% of the administered compound was biotransformed into C23 bile acids. The major C23 metabolites in bile were norchenodeoxycholic acid (17%), tauronorchenodeoxycholic acid (33%), and a trihydroxy norbile acid (identified as 3 alpha, 5 beta, 7 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic acid, 19%). Small amounts (< 5%) of sulfate(s) and glucuronide(s) were also detected. Homochenodeoxycholic acid, when infused intravenously into the hamster, produced a striking choleresis. The increase in bile flow after infusion of this compound was 6- to 7-times that induced by chenodeoxycholic acid. The apparent choleretic activity of homochenodeoxycholic acid, 181 microliters/mumol, was much greater than that of chenodeoxycholic acid, 11 microliters/mumol. In conclusion, homochenodeoxycholic acid induced a hypercholeresis of the same order of magnitude as norchenodeoxycholic acid, presumably because considerable proportions of this compound were degraded to the hypercholeretic norchenodeoxycholic acid via beta-oxidation in the liver. PMID- 8354958 TI - Effect of dietary cholesterol and taurocholate on cholesterol 7 alpha-hydroxylase and hepatic LDL receptors in inbred mice. AB - Compared to BALB/c mice, inbred C57BL/6 mice are more susceptible to developing fatty streak atherosclerotic lesions when fed a cholesterol-rich diet containing taurocholate. We examined the metabolic basis for the taurocholate requirement. In contrast to widely accepted assumptions, taurocholate did not increase cholesterol absorption in either strain of mouse. However, in susceptible C57BL/6 mice, taurocholate was required to increase plasma concentrations of apoB. In both strains, the cholesterol-rich diet increased both the activity and mRNA for 7 alpha-hydroxylase, a compensatory response to maintain cholesterol homeostasis. In both strains, adding taurocholate to the diet suppressed both the activity and mRNA for 7 alpha-hydroxylase, thus blocking this important compensatory response. The cholesterol-rich diet (without taurocholate) significantly increased hepatic cholesterol content in both strains of mice, but repressed low density lipoprotein (LDL) receptor mRNA only in BALB/c mice (not in C57BL/6 mice). However, adding taurocholate to the cholesterol-rich diet did decrease LDL receptor mRNA in C57BL/6 mice. In C57BL/6, but not in BALB/c mice, there was a linear parallel relationship between 7 alpha-hydroxylase mRNA and LDL receptor mRNA. These data show the existence of strain-specific differences in the effects of dietary cholesterol and taurocholate on 7 alpha-hydroxylase and LDL receptor expression. The combined data suggest that genetic factors determine how the expression of hepatic LDL receptors responds to dietary cholesterol and taurocholate. PMID- 8354959 TI - Dietary cholesterol stimulates hepatic biosynthesis of triglyceride and reduces oxidation of fatty acids in the rat. AB - Experiments were conducted in the intact rat and in the isolated, perfused rat liver to investigate the possibility that the increase in the concentration of hepatic triglyceride and increase in the secretion of the very low density lipoprotein (VLDL)-triglyceride (TG) resulting from addition of cholesterol to the diet are due to stimulation of synthesis of triglyceride, reduced fatty acid oxidation, or both. Male rats were fed for 7 days with either a cholesterol-free diet to which 5% (w/w) corn oil was added, or with the same diet supplemented with 0.5% cholesterol. Fed animals received [1-14C]oleic acid via the tail vein, as a complex with rat serum, and were killed 2 h later. Feeding cholesterol for 7 days increased hepatic triglyceride and cholesteryl ester (CE) concentrations, moderately elevated free cholesterol, but did not affect phospholipid (PL) levels, as we had previously observed after a feeding period of 3 weeks. Incorporation of [1-14C]oleic acid into hepatic and plasma triglyceride increased significantly (60 and 48%, respectively) with cholesterol feeding. Incorporation of [1-14C]oleic acid into hepatic and plasma cholesteryl esters increased by 63 and 79%, respectively, while incorporation into phospholipid was unaffected. Increasing the fat (corn oil) content of the diet to 20% (w/w) did not change these effects of dietary cholesterol. Studies using isolated, perfused rat livers were carried out in vitro after rats were fed the 5% corn oil diet for 3 weeks. [Perfusions lasted 4 h. The perfusion medium contained 3% bovine serum albumin and 30% washed bovine erythrocytes in Krebs-Henseleit-HCO3 buffer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354960 TI - Plasma lipoproteins in the golden Syrian hamster (Mesocricetus auratus): heterogeneity of apoB- and apoA-I-containing particles. AB - We present the quantitative and qualitative characteristics of the apolipoprotein (apo) B- and apoA-I-containing lipoprotein subspecies in the plasma of male Golden Syrian hamsters. The spectrum of hamster lipoproteins of d < 1.172 g/ml was subfractionated by isopycnic density gradient ultracentrifugation. ApoB containing subspecies were distributed up to a density of 1.074 g/ml. Hamster very low density lipoproteins (VLDL, d < 1.018 g/ml; approximately 120 mg/dl plasma) were triglyceride (TG)-rich, deficient in cholesteryl ester (CE), and highly heterogeneous in size, containing chylomicron-like particles. ApoVLDL contained proteins analogous to human apoB-100, apoB-48, and apoE. ApoB containing subspecies with physicochemical properties typical of low density lipoproteins (LDL) were identified as a single, major size species in the density interval from 1.019 to 1.074 g/ml, particle diameter decreasing progressively with increase in density. Hamster LDL-like subspecies were distinguished from their human counterparts by a relative deficiency in core CE (< 30% by wt) and by enrichment in triglyceride. The high M(r) form of apoB was the major apolipoprotein of all LDL-like subfractions, in which apoE was detected as a minor component. Total plasma levels of LDL (d 1.019-1.074 g/ml) amounted to approximately 140 mg/dl (approximately 25% of d < 1.172 g/ml lipoproteins). The distribution of dense apoB-containing subspecies overlapped that of apoA-I containing, high density lipoprotein-1 (HDL1)-like particles in the density interval approximately 1.039-1.074 g/ml. ApoA-I-containing subspecies with the physical and chemical characteristics of HDL were exclusively present over the density interval 1.074-1.172 g/ml. Quantitatively, these subspecies predominated in hamster plasma (approximately 270 mg/dl). Light, HDL2-like particles of d 1.065-1.103 g/ml (HDLL) were preponderant, (approximately 66% of total HDL). Marked size heterogeneity was evident, and was associated with distinct particle contents of minor apolipoproteins. Both HDLL and heavy HDL (HDLH, d 1.103-1.172 g/ml) were enriched in CE as evidenced by elevated weight ratios of CE:FC (7-9:1) and of CE:TG (up to approximately 50:1). Considered together, the core lipid contents of apoB- and apoA-I-containing lipoproteins are consistent with the hypothesis that the hamster is partially deficient in neutral lipid (CE, TG) transfer activity. PMID- 8354961 TI - Regulation of hepatic triglyceride lipase by thyroid hormone in HepG2 cells. AB - Hypothyroidism has been reported to be associated with reduced hepatic triglyceride lipase (HTGL) activity. In order to understand the molecular mechanism by which thyroid hormone regulates HTGL activity, effects of triiodothyronine (T3) on HTGL activity, mRNA level, transcription run-on activity, and protein synthetic rate were studied in HepG2 cells. HepG2 cells treated with 1 nM T3 showed an increase in HTGL activity that was first detected at 24 h; HTGL activity continued to increase at 36 h and stayed at the elevated level at 48 and 60 h. At maximal stimulation (48 h), T3-treated cells had the following HTGL activities: 155% in spontaneously released (SR) and 224% in heparin-releasable (HR) HTGL activities (mean levels compared to control). Stimulation of HTGL activity by T3 was dose-dependent and saturable. There was, however, no change in HTGL mRNA level throughout the course of T3 treatment. The effects of T3 were reduced when transcription was blocked by actinomycin D (mean level compared to actinomycin D treatment in the absence of T3: 109% in SR and 127% in HR activities) or translation was blocked by cycloheximide (127% in SR and 122% in HR activities), but HTGL activities were still significantly higher than control. Nuclear run-on assays indicate that T3 did not change the rate of transcription of the HTGL gene. We further determined the rate of HTGL synthesis by measuring the amount of [35S]methionine incorporated into newly synthesized HTGL immunoprecipitated by a monospecific anti-human HTGL antibody. We found that the T3-stimulated increase in HTGL activity was not accompanied by any change in the rate of HTGL biosynthesis. Our experimental data indicate that the T3 stimulation of HTGL activity in HepG2 cells is mediated at posttranscriptional and posttranslational levels. The partial but significant inhibition of the T3 stimulation of HTGL activity by actinomycin D and cycloheximide suggests that the effects of T3 may be mediated by other cellular processes that are more directly regulated by the hormone. This study represents the initial report on the mechanism of HTGL activation by physiological concentrations of thyroid hormone. PMID- 8354962 TI - Apolipoprotein B-52 mutation associated with hypobetalipoproteinemia is compatible with a misaligned pairing deletion mechanism. AB - We have identified a new truncation of apoB in a large kindred with hypobetalipoproteinemia that arose by an ambiguous deletion of one of four different groups of base-pairs. Eleven affected members of the kindred had total cholesterols (C) of 114 +/- 28, LDL-Cs of 46 +/- 21, and apoBs of 47 +/- 25 (all in mg/dl, mean +/- SD). These levels were lower (P < 0.0001) than in 15 unaffected relatives. On Western blotting, apoB-100 and a second major band corresponding to apoB-52 were seen in the affected individuals. The majority of the plasma apoB-52 was associated with a smaller than normal low density lipoprotein (LDL) particle. The molecular basis for this apoB-52 truncation is a 5-bp deletion, converting the sequence between cDNA nucleotide 7276 and 7283 from 5'-AAGTTAAG-3' into the mutant sequence 5'-AAG-3'. This results in a frameshift starting at amino acid residue 2357 and a termination codon at amino acid residue 2362. Deletion of one of four different groups of five consecutive bases, i.e., AAGTT, AGTTA, GTTAA, and TTAAG, all result in the same mutant sequence. Thus, the precise deletion is ambiguous. We propose that a misaligned pairing mechanism involving repeat sequences is compatible with this deletion mutation. We have noted similar ambiguous deletions associated with apoB-37, apoB-40, and a number of single base deletions and some may also be explained by a misaligned pairing mechanism. Small ambiguous deletions appear to constitute a major proportion of the apoB gene mutation spectrum suggesting that it may be a suitable model for studying the mechanisms of such mutations. PMID- 8354963 TI - Behavior systems and reinforcement: an integrative approach. AB - Most traditional conceptions of reinforcement are based on a simple causal model in which responding is strengthened by the presentation of a reinforcer. I argue that reinforcement is better viewed as the outcome of constraint of a functioning causal system comprised of multiple interrelated causal sequences, complex linkages between causes and effects, and a set of initial conditions. Using a simplified system conception of the reinforcement situation, I review the similarities and drawbacks of traditional reinforcement models and analyze the recent contributions of cognitive, regulatory, and ecological approaches. Finally, I show how the concept of behavior systems can begin to incorporate both traditional and recent conceptions of reinforcement in an integrative approach. PMID- 8354964 TI - Delay reduction: current status. AB - Delay-reduction theory states that the effectiveness of a stimulus as a conditioned reinforcer may be predicted most accurately by the reduction in time to primary reinforcement correlated with its onset. We review support for the theory and then discuss two new types of experiments that assess it. One compares models of choice in situations wherein the less preferred outcome is made more accessible; the other investigates whether frequency of conditioned reinforcement affects choice beyond the effect exerted by frequency of primary reinforcement. PMID- 8354965 TI - A selectionist approach to reinforcement. AB - We describe a principle of reinforcement that draws upon experimental analyses of both behavior and the neurosciences. Some of the implications of this principle for the interpretation of behavior are explored using computer simulations of adaptive neural networks. The simulations indicate that a single reinforcement principle, implemented in a biologically plausible neural network, is competent to produce as its cumulative product networks that can mediate a substantial number of the phenomena generated by respondent and operant contingencies. These include acquisition, extinction, reacquisition, conditioned reinforcement, and stimulus-control phenomena such as blocking and stimulus discrimination. The characteristics of the environment-behavior relations selected by the action of reinforcement on the connectivity of the network are consistent with behavior analytic formulations: Operants are not elicited but, instead, the network permits them to be guided by the environment. Moreover, the guidance of behavior is context dependent, with the pathways activated by a stimulus determined in part by what other stimuli are acting on the network at that moment. In keeping with a selectionist approach to complexity, the cumulative effects of relatively simple reinforcement processes give promise of simulating the complex behavior of living organisms when acting upon adaptive neural networks. PMID- 8354966 TI - Response acquisition under targeted percentile schedules: a continuing quandary for molar models of operant behavior. AB - The number of responses rats made in a "run" of consecutive left-lever presses, prior to a trial-ending right-lever press, was differentiated using a targeted percentile procedure. Under the nondifferential baseline, reinforcement was provided with a probability of .33 at the end of a trial, irrespective of the run on that trial. Most of the 30 subjects made short runs under these conditions, with the mean for the group around three. A targeted percentile schedule was next used to differentiate run length around the target value of 12. The current run was reinforced if it was nearer the target than 67% of those runs in the last 24 trials that were on the same side of the target as the current run. Programming reinforcement in this way held overall reinforcement probability per trial constant at .33 while providing reinforcement differentially with respect to runs more closely approximating the target of 12. The mean run for the group under this procedure increased to approximately 10. Runs approaching the target length were acquired even though differentiated responding produced the same probability of reinforcement per trial, decreased the probability of reinforcement per response, did not increase overall reinforcement rate, and generally substantially reduced it (i.e., in only a few instances did response rate increase sufficiently to compensate for the increase in the number of responses per trial). Models of behavior predicated solely on molar reinforcement contingencies all predict that runs should remain short throughout this experiment, because such runs promote both the most frequent reinforcement and the greatest reinforcement per press. To the contrary, 29 of 30 subjects emitted runs in the vicinity of the target, driving down reinforcement rate while greatly increasing the number of presses per pellet. These results illustrate the powerful effects of local reinforcement contingencies in changing behavior, and in doing so underscore a need for more dynamic quantitative formulations of operant behavior to supplement or supplant the currently prevalent static ones. PMID- 8354967 TI - Scaling pigeons' choice of feeds: bigger is better. AB - Preferences of hungry pigeons among 10 grains and pellets were analyzed using a Thurstone scaling procedure. The recovered scales were positively correlated with size of the feed. The correlations improved when the Thurstonian assumption of equal-sized discriminal dispersions (Case V) was replaced with the assumption of proportional-sized dispersions (Case VI), as entailed by Weber's law. The correlations weakened when the experiments were conducted with the pigeons close to their free-feeding weights, where the probability of sampling alternative grains increased. In the final experiment, exposure to a large pellet shifted the preferences between two smaller pellets. PMID- 8354968 TI - Techniques for establishing schedules with wheel running as reinforcement in rats. AB - In three experiments, access to wheel running was contingent on lever pressing. In each experiment, the duration of access to running was reduced gradually to 4, 5, or 6 s, and the schedule parameters were expanded gradually. The sessions lasted 2 hr. In Experiment 1, a fixed-ratio 20 schedule controlled a typical break-and-run pattern of lever pressing that was maintained throughout the session for 3 rats. In Experiment 2, a fixed-interval schedule of 6 min maintained lever pressing throughout the session for 3 rats, and for 1 rat, the rate of lever pressing was positively accelerated between reinforcements. In Experiment 3, a variable-ratio schedule of 20 or 35 was in effect and maintained lever pressing at a very stable pace throughout the session for 2 of 3 rats; for 1 rat, lever pressing was maintained at an irregular rate. When the session duration was extended to successive 24-hr periods, with food and water accessible in Experiment 3, lever pressing settled into a periodic pattern occurring at a high rate at approximately the same time each day. In each experiment, the rats that developed the highest local rates of running during wheel access also maintained the most stable and highest rates of lever pressing. PMID- 8354969 TI - A cellular analogue of operant conditioning. AB - Using the hippocampal-slice preparation, we attempted to model operant conditioning in vitro by reinforcing pyramidal cell bursting responses with local micropressure applications of transmitters and drugs. The same injections were administered independently of bursting to provide a "noncontingent" control for direct pharmacological stimulation or facilitation of firing. The results suggested that the bursting responses of individual CA1 pyramidal neurons may be reinforced in a dose-related manner by response-contingent (but not noncontingent) injections of dopamine and the selective dopamine D2 agonist, N 0923. N-0924, a stereoisomer of N-0923 that is largely devoid of D2-agonist activity, failed to reinforce CA1 bursting. Burst-contingent injections of the excitatory neurotransmitter glutamate also failed to reinforce CA1 bursting; indeed, the glutamate applications (whether contingent or random) reduced the likelihood of bursts while increasing the frequency of solitary spikes. Reinforcement delays exceeding 200 ms largely eliminated the reinforcing efficacy of the D2 agonist N-0437 in CA1 operant conditioning. The results are consistent with the suggestion that the behaviorally reinforcing effects of dopaminergic agents can be modeled in vitro in the hippocampal-slice preparation. PMID- 8354971 TI - Reversibility of single-incentive selective associations. AB - Rats were trained to press a lever in the presence of a tone-light compound stimulus and not to press in its absence. In each of two experiments, schedules were designed to make the compound a conditioned punisher for one group and a conditioned reinforcer for the other. In Experiment 1, one group's responding produced food in the presence of the compound but not in its absence. The other group's responding terminated the compound stimulus, and food was presented only in its absence. When tone and light were later presented separately, light controlled more responding than did tone in the former group, but tone gained substantial control in the latter. The same effects were also observed within subjects when the training schedules were switched over groups. In Experiment 2, two groups avoided shock in the presence of the compound stimulus. In the absence of the compound, one group was not shocked, and the other received both response independent and response-produced shock. When tone and light were presented separately, the former group's responding was mainly controlled by tone, but the latter group's responding was almost exclusively controlled by light. These effects were also observed within subjects when the training schedules were switched over groups. Thus, these single-incentive selective association effects (appetitive in Experiment 1 and aversive in Experiment 2) were completely reversible. The schedules in which the compound should have been a conditioned reinforcer consistently produced visual control, and auditory control increased when the compound should have become a conditioned punisher. Currently accepted accounts of selective associations based on affinities between shock and auditory stimuli and between food and visual stimuli (i.e., stimulus-reinforcer interactions) do not adequately address these results. The contingencies of reinforcement most recently associated with the compound and with its absence, rather than the nature of the reinforcer, determined whether auditory or visual stimulus control developed. PMID- 8354970 TI - The nature of sexual reinforcement. AB - Sexual reinforcers are not part of a regulatory system involved in the maintenance of critical metabolic processes, they differ for males and females, they differ as a function of species and mating system, and they show ontogenetic and seasonal changes related to endocrine conditions. Exposure to a member of the opposite sex without copulation can be sufficient for sexual reinforcement. However, copulatory access is a stronger reinforcer, and copulatory opportunity can serve to enhance the reinforcing efficacy of stimulus features of a sexual partner. Conversely, under certain conditions, noncopulatory exposure serves to decrease reinforcer efficacy. Many common learning phenomena such as acquisition, extinction, discrimination learning, second-order conditioning, and latent inhibition have been demonstrated in sexual conditioning. These observations extend the generality of findings obtained with more conventional reinforcers, but the mechanisms of these effects and their gender and species specificity remain to be explored. PMID- 8354972 TI - Fort Knox and the open scientific landscape. PMID- 8354973 TI - Glucocorticoid-induced osteoporosis: pathogenesis, prevention and treatment, with special regard to the rheumatic diseases. AB - OBJECTIVES: To review factors associated with development of osteoporosis in patients with rheumatic diseases, as well as the preventive and therapeutic measures. DESIGN: A MEDLINE literature search. RESULTS: 1 Pathogenesis. Rheumatoid arthritis in itself causes reduction of bone mass; this process can be aggravated by glucocorticoid treatment. With glucocorticoid treatment, bone mineral density decrease is most pronounced during the first months of treatment. There is no agreement on the effects of daily dose, cumulative dose, and duration of glucocorticoid treatment on the rate of bone loss. However, with treatment by low doses (< 10 mg of prednisone equivalent per day), bone loss appears to be minimal or even undetectable compared to controls. Alternate day treatment, or treatment with steroid 'pulses' have not been shown to protect from bone loss. 2 Prevention and treatment. Prophylactic and therapeutic measures for glucocorticoid-induced osteoporosis include calcium supplementation, vitamin D in physiological doses and oestrogen in perimenopausal female patients. Efficacy has not always been shown in this particular indication but is extrapolated from other forms of osteoporosis. Limited data exist on treatment with anabolic steroids, calcitonin (with an additional analgesic effect) and biphosphonates and reduction of fracture rates has not yet been investigated. At present, there is insufficient evidence to show that altered steroid molecules can dissociate adverse effects on bone from clinically desirable effects. CONCLUSION: In view of the paucity of study data, prophylaxis and therapy of glucocorticoid-induced osteoporosis should receive more attention in future clinical studies. PMID- 8354974 TI - Effects of weight loss on pulmonary function in obese men with obstructive sleep apnoea syndrome. AB - The effects of long-term behaviour modification of obesity on pulmonary function was studied in eight men with obstructive sleep apnoea syndrome (initial mean body mass index [BMI] 41.8 kg m-2) before and after a mean weight loss of 20 +/- 7 (SD) kg. Mean arterial PCO2 fell from 6.3 +/- 1.2 to 5.5 +/- 0.6 kPa (P < 0.05) and concomitant significant improvements were found in vital capacity, total lung capacity, functional residual capacity and forced expired volume (FEV 1.0). The study suggests that weight loss per se, rather than the method of choice to achieve weight loss, results in clinically significant improvement of pulmonary function in obese men. PMID- 8354975 TI - Progressive renal failure in patients with lupus nephritis. AB - OBJECTIVE: To investigate the mode of progression to renal failure in patients with lupus nephritis in relation to disease activity and responsiveness to corticosteroid therapy. DESIGN: Retrospective clinical study. SETTING: University hospital. SUBJECTS: Twenty-eight patients with progressive lupus nephritis (Cr > or = 1.4 mg dl-1). INTERVENTIONS: Rapidity of progression was defined as the slope of the reciprocal of serum creatinine values. Lupus activity was scored using the systemic lupus erythematosus disease activity index system. MAIN OUTCOME MEASURES: Improvement of serum creatinine values after 6 months of therapy. RESULTS: Rapidity of progression, which was calculated during the deterioration in kidney function, reflected systemic and serological disease activity, and moreover closely correlated with response to corticosteroid therapy. PMID- 8354976 TI - High serum insulin, insulin resistance and their associations with cardiovascular risk factors. The northern Sweden MONICA population study. AB - OBJECTIVES: To estimate the prevalence of insulin resistance and high serum insulin levels and to investigate their relationship to other cardiovascular risk factors. DESIGN: Cross-sectional cardiovascular risk factor survey. SETTING: Northern Sweden. SUBJECTS: A subsample of the population-based Northern Sweden MONICA Study. This subsample underwent an oral glucose tolerance test after an overnight fast, and consisted of 354 men and 404 women in the 25-64-year age range. MAIN OUTCOME MEASURES: Delineation of low insulin sensitivity and high serum insulin by the diagnostic test technique, prevalence of these variables and their associations with cardiovascular risk factors. RESULTS: The participants were classified into four subgroups by an insulin sensitivity index and fasting serum insulin. The combination of low insulin sensitivity and high serum insulin was present in 17% of the male and in 18% of the female 25-64-year-old population. In both sexes this combination was closely associated (P < 0.001) with body mass index, waist-hip ratio, blood pressure and serum triglycerides, and correlated inversely with serum HDL cholesterol (P < 0.001). When high serum insulin was present as an isolated entity it was as closely associated with other cardiovascular risk factors such as isolated low insulin sensitivity, except that impaired glucose tolerance occurred exclusively in the group with isolated low insulin sensitivity. CONCLUSIONS: The combination of insulin resistance and high insulin levels is associated with a marked clustering of cardiovascular risk factors and is present in one-sixth of the middle-aged population in the north of Sweden. PMID- 8354977 TI - The influence of antihypertensive therapy on the structural arteriolar changes in essential hypertension: different effects of enalapril and hydrochlorothiazide. AB - OBJECTIVES: To assess the peripheral and central haemodynamics, in particular the effect on minimal resistance in the hand, with an ACE inhibitor in comparison with a diuretic. DESIGN: Double-blind randomized parallel group study. SUBJECTS: Twenty-eight previously untreated men with essential hypertension (supine diastolic blood pressure > 95 mmHg repeatedly on placebo). METHODS/INTERVENTION: Causal and intra-arterial blood pressure, dye-dilution technique, water plethysmography at rest and at ischaemia, enalapril (n = 14), hydrochlorothiazide (n = 14). RESULTS: After 6 months the mean arterial pressure was reduced from 112.7 to 96.9 mmHg (change -15.9 mmHg; 95% confidence interval (CI) -21.9, -9.8) on enalapril and from 110.1 to 101.5 mmHg (change -8.6 mmHg; CI -14.4, -2.8). Heart rate did not change on any of the therapies. Enalapril reduced blood pressure mainly through a reduction in total peripheral resistance (delta -3.0 PRU100; CI -5.6, -0.4) while hydrochlorothiazide reduced blood pressure mainly through a reduction in cardiac output (delta -0.8 l/min-1; CI -1.5, -0.07). Minimal vascular resistance (mean of right and left hand) displayed a significant time x treatment interaction indicating a different trend with enalapril than hydrochlorothiazide with a change of -0.12 PRU100 (CI -0.33, 0.05) on enalapril and a change of 0.14 (CI -0.29, 0.56) on hydrochlorothiazide. The resistance level after 6 months was significantly higher on hydrochlorothiazide than on enalapril (P = 0.0105). CONCLUSION: Enalapril reduced blood pressure through vasodilatation and hydrochlorothiazide through decreased cardiac output. The two therapies also affected minimal vascular resistance (an indirect measure of vascular wall thickness) differently; with enalapril showing a favourable response in contrast to hydrochlorothiazide. PMID- 8354978 TI - Determination of urinary N-acetyl-beta-glucosaminidase in patients with hypertension and renal artery stenosis. AB - The purpose of the study was to measure the urinary excretion of N-acetyl-beta glucosaminidase (U-NAG) in patients suspected of having renovascular hypertension and to compare the enzyme excretion before and after active intervention with operation or percutaneous transluminal renal angioplasty (PTRA). Eighty-one patients with severe, therapy-resistant hypertension were examined with regard to renal artery stenosis (RAS). At least one significant renal artery stenosis was found in 61 patients, whilst the remaining 20 patients were classified as having essential hypertension. Enzyme levels were found to be significantly higher in RAS patients as compared with patients with severe hypertension lacking significant renal artery stenosis, 0.66 (0.41-0.91, median value, 1st and 3rd quartiles) versus 0.35 (0.27-0.54); P < 0.01. Both groups of patients had significantly higher U-NAG values than a healthy reference population (0.2, 0.13 0.27; P < 0.01). Forty of the RAS patients were randomized to surgery or PTRA and followed prospectively for 2 years. After either renal vascular surgery or PTRA a significant rise in U-NAG excretion was observed 7-10 days after treatment. Urinary NAG excretion remained elevated during long-term follow-up. It is suggested that U-NAG should be determined in patients with therapy-resistant hypertension with suspicion of renal artery stenosis. PMID- 8354980 TI - Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease. The RISC Study Group. AB - OBJECTIVES: To determine the possibility of very early prognostic stratification based on electrocardiograms (ECGs) at rest and/or cardiac enzyme levels after an episode of suspected unstable coronary heart disease. DESIGN AND SETTING: Men with suspected unstable angina or non-Q-wave myocardial infarction were studied in the coronary care units of eight hospitals. The ECGs at rest and creatinine kinase were followed. SUBJECTS: In total 911 men were followed for 12 months. Of 8136 consecutively admitted, 3365 fulfilled the inclusion criteria. Excluded were 2454 patients, mainly because of a larger myocardial damage, signs of myocardial dysfunction, other serious cardiac or non-cardiac disease or an ECG not possible to interpret regarding ST-T-segment changes in the precordial leads. MAIN OUTCOME MEASURES: End-points at follow-up were cardiac death, myocardial infarction and severe (class III or IV) angina. RESULTS: Compared to patients with normal a ECG who had an 8% 1-year risk of myocardial infarction or death, the risk with isolated negative T waves was 14% (P < 0.05), ST elevation 16% (P < 0.05), ST depression 18% (P < 0.01) and the combination of ST elevation and ST depression 26% (P < 0.001). The only finding related to future severe angina was ST depression. The risk of cardiac events was comparably elevated in patients with anterior or inferior site of ECG changes. Cardiac enzyme levels had no predictive value regarding future events. CONCLUSIONS: Electrocardiograms at rest obtained during the initial days of hospitalization provide very early and valuable prognostic information in men admitted with suspected unstable coronary heart disease. PMID- 8354979 TI - Liver damage from low-dose oral contraceptives. AB - OBJECTIVE: To study whether the decrease in the content of oestrogen and gestagen in modern low-dose oral contraceptives (OC) has yielded a lower incidence of adverse liver reactions, and to describe the biochemical pattern of the adverse liver reactions from low-dose OC. DESIGN: We surveyed all liver reactions from OC reported to SADRAC (Swedish Adverse Drug Reactions Advisory Committee) from 1966 to 1989. MAIN OUTCOME MEASURE: Incidence of reported adverse liver reactions (number of reported adverse reactions/OC sales in defined daily dose [DDD]). RESULTS: There was a sharp decline in the number of reports during the studied period, suggesting changes in reporting habits. However, there was also a significantly lower incidence of reports for medium-compared to high-oestrogen dose OC, and a further decrease, albeit non-significant, in incidence with low oestrogen dose OC. Furthermore, in three comparisons of pairs of OC that differed only in the gestagen dose, there was a strong trend towards a higher reporting rate with higher gestagen dose. Cholestatic and hepatocellular liver enzyme patterns were equally frequent in patients with adverse reactions from low-dose oestrogen OC. There was no report of liver tumours related to use of low oestrogen dose OC. CONCLUSION: There seems to be a decrease in the incidence of adverse liver reactions related to lower contents of both oestrogen and gestagens in OC of the combined-preparation type. PMID- 8354981 TI - Low-dose warfarin decreases coagulability without affecting prothrombin complex activity. AB - OBJECTIVES: To assess the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII:C) and to investigate the effects on the plasma coagulation cascade. DESIGN: An open pilot study with two dose levels of warfarin: 1.25 and 2.5 mg day-1 during two consecutive 4-week periods. All subjects received aspirin 75 mg day-1. Prothrombin fragment 1 + 2 (F(1 + 2)), protein C, protein S, FVII:C, factor X and P-prothrombin complex activity (P-PT) were measured at baseline, at 2-week intervals and 4 weeks after end of treatment. Coagulation activation peptide F(1 + 2) was used as a marker of thrombin formation. SUBJECTS: Twelve male patients with a history of myocardial infarction. Inclusion was made through a written questionnaire. RESULTS: Warfarin 1.25 mg day-1 lowered FVII:C from 113 U dl-1 to 107 U dl-1 (P = 0.025) and F(1 + 2) from 1.60 nmol l-1 to 1.27 nmol l-1 (P = 0.013) but had no effect on protein C or P-PT. A dose of 2.5 mg day-1 induced further lowering of FVII:C (91 U dl-1, P = 0.0042), and also of protein C from 116% to 99% (P = 0.034) and P-PT from 107% to 81% (P = 0.0096) mean values. CONCLUSION: Warfarin 1.25 mg day-1 seems to exert an anticoagulant effect without reduction in PT or the natural anticoagulant protein C and is suggested, in combination with aspirin, to be a safe and simple therapy against arterial thrombotic disease, making regular PT controls unnecessary. PMID- 8354982 TI - Tracking of cardiovascular disease risk factors including maximal oxygen uptake and physical activity from late teenage to adulthood. An 8-year follow-up study. AB - OBJECTIVES: The aim of the study was to analyse changes in coronary heart disease (CHD) risk factors from adolescence to young adulthood, and how changes in risk factors relate to changes in lifestyle. DESIGN: A randomized sample of school children was tested in 1983 and followed-up 8 years later. In 1983 a dropout of 0.7% was found and the sample was representative of 16-19-year-old Danes. SUBJECTS: Subjects followed-up 8 years later (two-thirds of the original sample) were 88 male and 115 female 15-19-year-old school children attending 18 high schools, nine vocational and nine trade schools, throughout Denmark. MAIN OUTCOME MEASURES: Height, body weight, body fat, occupation and coronary heart disease risk factors including physical activity (PA), fitness, blood pressure (BP), serum cholesterol, HDL cholesterol, triglyceride (TG) and smoking habits were assessed. RESULTS: In males all risk factors increased: the increases in total cholesterol level and systolic and diastolic BP were large, 0.85 mmol l-1 and 11 mmHg, respectively. In females, the risk for some factors increased (total cholesterol and BP), others decreased (higher HDL cholesterol), and triglyceride did not change. Significant tracking was found in both sexes, with the highest correlation coefficients in men. A total risk score was calculated by categorizing risk factors into six groups--1 to 6--and then adding the scores. Pearson correlation between the total risk scores in 1983 and 1991 in men was r = 0.67 (P < 0.001). Only a weak association was found for the total risk score in women. Nearly 50% of the boys, who were initially in the upper quintile of risk, were still in the upper quintile 8 years later for most risk factors. In men, the changes in risk factors were related to social factors. Blue-collar workers and the unemployed had the highest increase in risk factors, and the largest decrease in VO2max (ml min-1 kg-1) when analysed together. In both sexes the best relationship between 1983 and 1991 values was found in body mass index (BMI). Leisure time physical activity (PA) and triglyceride (TG) had a low correlation between 1983 and 1991 values. Physical activity had a non-significant correlation over time for women, indicating that PA in 1983 did not predict PA in 1991 at all. CONCLUSION: Coronary heart disease risk factors tracked in both males and females, but only in males was a strong relationship found for total risk from adolescence to young adulthood, indicating the influence of a poor lifestyle in high-risk men. Lower social status related to higher risk. PMID- 8354983 TI - The cost-effectiveness of treating hypertension in elderly people--an analysis of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension). AB - OBJECTIVES: The aim of this study was to estimate the cost-effectiveness of antihypertensive treatment in elderly people based on the results of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension). DESIGN: The STOP Hypertension study was a randomized trial comparing active antihypertensive treatment with a placebo. The risk of stroke, cardiovascular disease and total mortality was significantly reduced in the actively treated group compared to placebo. SETTING: One hundred and sixteen primary health care centres in Sweden. SUBJECTS: A total of 1627 hypertensive patients aged 70-84. No patient was lost to follow-up. INTERVENTIONS: Antihypertensive treatment with beta blockers and diuretics for a mean follow-up of 25 months. MAIN OUTCOME MEASURE: The cost effectiveness ratio estimated as the net cost (the treatment cost minus saved costs of reduced cardiovascular morbidity) divided by the number of life-years gained (the increase in life expectancy from treatment). RESULTS: The cost per life-year gained was estimated as SEK 5000 for men and SEK 15,000 for women ($1 = SEK 6; 1 pound = SEK 10). The cost per life-year gained did not exceed SEK 100,000 in any of the sensitivity analyses. CONCLUSIONS: It is concluded that treatment of elderly hypertensive patients with beta blockers and/or diuretics is cost-effective according to the results of the STOP Hypertension study. PMID- 8354984 TI - Non-paroxysmal arterioventricular junctional tachycardia during postprandial hypoglycaemia in an obese non-diabetic patient. AB - We have observed the simultaneous occurrence of postprandial hypoglycaemia and a rare cardiac arrhythmia: non-paroxysmal arteriovenous junctional tachycardia (NPJT) in a patient with suspected coronary heart disease (CHD) submitted to oral glucose tolerance testing (OGTT). To our knowledge the association between hypoglycaemia and NPJT has not been previously described. The pathogenesis of NPJT might involve a myocellular Ca2+ overloading determined by a hypoglycaemia induced catecholamine discharge in a transiently ischaemic myocardium. PMID- 8354985 TI - Spontaneous resolution of acquired factor X deficiency in amyloidosis. AB - We describe the case of a 51-year-old man with systemic amyloidosis in whom factor X activity was initially 6% of the normal. Amyloidosis was responsible for congestive heart failure and a nephrotic syndrome but there was no bleeding diathesis. A 12-month trial of melphalan and prednisone failed to improve cardiac and renal dysfunction; factor X levels remained low. Eighteen months after this treatment was stopped, factor X spontaneously normalized although renal insufficiency persisted. We suggest that the possibility of a spontaneous factor X recovery must be considered when evaluating efficacy of therapeutic agents in amyloidosis. PMID- 8354986 TI - Essential cryofibrinogenaemia, leukocytoclastic vasculitis and chronic purpura. AB - Cryofibrinogenaemia refers to the presence of cold-precipitable proteins in plasma but not in serum. It is usually associated with malignancy, thromboembolic diseases or various inflammatory processes; rarely it may be essential. The most common clinical presentations of cryofibrinogenaemia are cold-intolerance, purpura, skin necrosis and ulcers. We describe a middle-aged woman with essential cryofibrinogenaemia, leukocytoclastic vasculitis, and chronic purpura for over 25 years with several exacerbations. In patients with otherwise unexplained purpura or skin necrosis, determination of plasma cryofibrinogen should be considered. PMID- 8354987 TI - Survival analysis of 118 patients with systemic sclerosis. AB - Life-table analysis based on the survival statistics of 118 Hungarian patients with systemic sclerosis suggests that the presence of skin hypo- and/or hyperpigmentation indicates a poor prognosis. Furthermore, truncal skin involvement, lung, cardiac, and renal manifestations, older age at the onset of disease, anaemia, hand deformity, and elevated erythrocyte sedimentation rate values, predict an unfavourable prognosis, whilst patients with exposure to chemicals shows a relatively favourable disease outcome. PMID- 8354988 TI - Angiotensin-converting enzyme inhibition and physical training in heart failure. PMID- 8354989 TI - Lack of evidence of exon 13 mutations in the beta cardiac myosin heavy chain gene with familial hypertrophic cardiomyopathy in Japan. PMID- 8354990 TI - Physiological response of Zebu and taurine oxen to draught work. AB - Four Zebu and four Simmental oxen were submitted to continuous and to graded draught work. Venous blood samples were taken before, during, and after exercise at intervals of 2-5 min. Anaerobic threshold was reached at a draught power of 1.6 +/- 0.06 kW for Zebu and 0.7 +/- 0.07 kW for Simmental. Corresponding plasma lactate concentrations were 1.7 +/- 0.2 mmol/liter and 1.6 +/- 0.3 mmol/liter, respectively. Partial pressure of oxygen (pvO2), carbon dioxide (pvCO2), and plasma free fatty acids (FFA) during and after work differed between breeds (P approximately .001) and individuals (P approximately .05). After work, an up to 8 fold increase in FFA was found. Highest plasma lactate concentrations during continuous maximal draught were 3.75 +/- 1.76 (Zebu) and 6.01 +/- 0.88 mmol/liter (Simmental). Acid-base-state during and after exhaustive work remained stable. Heart rate in both breeds did not exceed 190 min-1. It is concluded that 1) even during heavy draught work, anaerobic energy formation plays a minor role for cattle, 2) fatigue in working oxen may be related to cardiovascular limitations, and 3) the physical fitness of European beef-breed oxen is lower compared to multipurpose African Zebu oxen. PMID- 8354991 TI - Two GnRHs fluctuate in correlation with androgen levels in the male frog Rana esculenta. AB - ChickenII-(cII-) and salmon (s-) GnRH levels have been measured in the male frog Rana esculenta during the annual cycle. The presence of pituitary binding activity for both peptides and plasma androgen levels has been investigated in order to give insight into the significance of the dual control exerted by the GnRH forms present in the R. esculenta brain. ChickenII- and s-GnRHs showed high values during the spring-summer period. Conversely, while cII-GnRH peaked in February, s-GnRH declined slowly from February until May. Plasma androgen levels increased as the peptides decreased during the autumn-winter period. Still high androgen levels (but significantly lower as compared with winter concentrations) were found during spring. Using iodinated cII-GnRH, GnRH binding sites were detected in pituitary preparations when the corresponding peptide concentration decreased in the brain. On the contrary, no binding sites were found using labeled s-GnRH. Our results indicate that cII-GnRH has a hypophysiotropic activity, while the role of s-GnRH needs to be further investigated. PMID- 8354992 TI - Effects of prolactin, growth hormone, and triiodothyronine on prolactin receptors in larval and adult tiger salamanders (Ambystoma tigrinum). AB - The effects of porcine growth hormone (pGH) or ovine prolactin (oPRL) alone and in combination with triiodothyronine (T3) on renal PRL receptors were determined in both pre- and post-metamorphic tiger salamanders (Ambystoma tigrinum). The protein hormones were given at a dose of 1.0 micrograms/gm body weight/day and the T3 was given at 10.0 ng/gm body weight/day. The duration of treatment was 7 days. Effects on growth, and plasma thyroid hormone levels were also determined. Ovine PRL increased growth in both larvae and adults and reversed metamorphic changes. Administration of T3 increased the plasma T3 concentration, as measured by radioimmunoassay, and when given alone caused weight loss at both stages. The GH decreased plasma T4 and increased plasma T3 concentrations, indicating that it caused an increase in T4 deiodination. In adults the renal PRL receptor affinity of 2.9 +/- 0.7 x 10(10) L/mol and capacity of 160 +/- 22 fmol/mg protein were higher than the corresponding values of 1.8 +/- 0.3 x 10(10) L/mol and 29.2 +/- 3.8 fmol/mg in larvae. In adults only, there is an additional low-affinity, high capacity PRL binding site. The oPRL treatment decreased the binding capacity of 33.2 +/- 1.2 and 5.9 +/- 4.9 fmol/mg in adults and larvae, respectively. By contrast, pGH increased the capacities to 249 +/- 18 and 62.1 +/- 6.8 fmol/mg in adults and larvae, respectively. Treatment with T3 alone doubled the oPRL binding capacity to 58.3 +/- 4.7 fmol/mg in larvae, but there was no effect in adults. In both developmental stages the effects of oPRL and pGH on the receptors were not changed by the simultaneous T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8354993 TI - Detection of insulin receptors in newt liver and forelimb regenerates and the effects of local insulin deprivation on epimorphic regeneration. AB - Previous in vivo and in vitro studies indicate that insulin is required in adult newt forelimb regeneration. The objectives of the current study were 1) to detect insulin receptors in the liver (a classical target organ for insulin) and once verified, detection of insulin receptors in the adult newt forelimb regenerate; and 2) to determine whether locally implanting insulin antibody-soaked hydrolyzed polyacrylamide beads (hypa beads) into a regenerating forelimb blastema would affect its growth and/or differentiation. The results show that insulin receptors are detectable in the plasma membranes of newt liver and forelimb regenerates. Radioiodinated bovine insulin binding is time-dependent and specific; unlabeled bovine insulin competes with labeled insulin for binding to NLPM more effectively than does insulin-like growth factor-I, guinea pig insulin, and glucagon. The newt hepatic insulin receptor binds insulin with high affinity (1.1 nM-1) and low capacity (63 +/- 8 fmoles/mg). The size of the alpha subunit of the newt insulin receptor is 130 kDA and that of the beta subunit is 95 kDa. The beta subunits undergo insulin-stimulated phosphorylation in response to insulin. An autoantibody against the human insulin receptor recognizes the newt receptor protein. Insulin receptors are also detectable in 15 and 20 day newt forelimb regenerates. Specific immunogold labelling of the receptor-bound antibody appears to be restricted to the cellular processes of the regenerate. Implanting hypa beads soaked with purified insulin antibody into regenerating adult newt forelimbs results in abnormal growth and differentiation of the regenerates, confirming that insulin plays an essential role in adult newt forelimb regeneration. PMID- 8354994 TI - Immunological detection of an oviductal glycoprotein in the rat. AB - In the golden hamster, high-molecular-weight glycoproteins are secreted by the epithelial cells of the oviduct. The present study was designed to investigate the possibility that the rat oviduct produces specific glycoproteins similar to the oviductal glycoproteins (GHOGPs) of the golden hamster. Oviductal extracts and oviductal fluids obtained from ovulatory rats were analysed by immunoblotting for the presence of glycoproteins that cross-react with a monoclonal antibody (MAb) against GHOGPs. The MAb immunoreacted with a broad band of proteins with a range of molecular weights (MWs) of above 330 kD in oviductal extracts or oviductal fluid after fractionation by electrophoresis under reducing conditions, but these proteins were not present in serum and uterine flushings. An immunohistochemical study demonstrated that the MAb bound strongly to the epithelial cells of the oviduct and, to a lesser extent, to those of the large intestine. Weak reactions were also observed with some other tissues. However, similar material of high MW was not detected in extracts of tissues from the other organs, suggesting that the glycoprotein of high MW that reacted with the MAb is specific for the oviduct. Ultrastructural immunocytochemistry revealed that the MAb reacted specifically with putative secretory granules of nonciliated cells in the oviductal epithelium. These results indicate that the oviductal epithelial cells of the rat produce a specific glycoprotein that is immunologically similar to GHOGPs. PMID- 8354995 TI - A simple technique for age estimation in adult corpses: the two criteria dental method. PMID- 8354996 TI - An anthropometric study of pedophiles and rapists. AB - Anthropometric measurements were obtained on pedophiles (n = 23) and rapists (n = 13) who were in a forensic treatment facility. Hand grip strength was measured with a Jamar hand dynamometer. Ten separate body measurements were taken including height and weight. As an indicator of body fat, triceps skinfold thickness was obtained with calipers on the non-dominant arm. The findings provided mild support for the hypothesis that the rapists in the sample would be stronger, more muscular, and have less body fat than the pedophiles. PMID- 8354997 TI - Sex determination from metacarpals and the first proximal phalanx. AB - Sex determination using metacarpals and the first proximal phalanx was carried out on a sample (n = 60) of documented sex. Six measurements were taken on each of metacarpals 1 to 5 and the first proximal phalanx. Regression equations were calculated for determining sex from the bones. The equations were then applied to a second sample (n = 20) also of documented sex to establish the degree of accuracy they produced in assigning sex. The equations for metacarpal 1 produced the highest degree of correct sex determination and overall the degree of accuracy ranged from 74% to 94%. PMID- 8354998 TI - Osteometry of the human iliac crest: patterns of normality and its utility in sexing human remains. AB - We recorded nine measurements and one index of the iliac crest in 42 human hip bones from a Spanish skeletal collection. Common values of seven of these parameters and index are reported. We could detect statistically significant differences of means depending on side for two of these parameters (iliac crest rise, distance from the upper point of the iliac crest to the anterior superior spine) and for the iliac crest index, and relating to sex for three parameters (iliac crest arch, iliac crest rise, distance from the upper point of the iliac crest to the anterior superior spine) and for the index. These measurements and index are useful for sexing human remains. PMID- 8354999 TI - Identification of rib number and assessment of intercostal variation at the sternal rib end. AB - A technique for the identification of anatomical rib number is presented here. Preliminary tests indicate that with experience, percent accuracy for identification may approach 100%. This technique was then applied to a skeletal collection where rib number was not documented in order to determine the effects of intercostal variation on the application of rib four age-at-death estimation standards to other ribs. Spearman rank correlations between rib four and ribs three through nine range from 0.89 to 0.91. No significant differences were found between ribs conforming to or deviating from the phase observed on rib four. There is a significant proportion of deviations falling below the phase set by rib four, however these deviations are not statistically associated with rib number and are usually within one phase. These results indicate that rib four standards can be cautiously applied to other sternal ends when rib four is not preserved. PMID- 8355000 TI - Determination of human immunodeficiency virus antibody status in forensic autopsy cases using a rapid and simple FDA-licensed assay. AB - Evaluation of an FDA-licensed rapid assay to detect antibodies to human immunodeficiency virus (HIV) was accomplished by testing 414 serum samples collected sequentially from autopsy cases at the Office of the Chief Medical Examiner, State of Maryland. The time of postmortem collection ranged from 8 to 30 hours. All samples were tested for the presence of antibodies to HIV using a rapid peptide microfiltration assay (SUDS HIV-1 test, Murex Corporation, Norcross, GA), and an enzyme-linked immunosorbent assay (ELISA). Samples yielding repeatedly reactive results were confirmed by Western blot. Of the 414 specimens, 23 (5.6%) produced reactive results by both SUDS and ELISA, and were confirmed by Western blot. One additional sample was repeatedly reactive by ELISA but negative by the SUDS test. This sample produced an indeterminate profile by Western blot (reactivity to only p24) and was negative by several additional retroviral assays. Of the 23 HIV infected cases, 16 had risk factors for HIV infection; 19 were blacks and 18 were male. The SUDS, 10 minute test, exhibited a 100% sensitivity and 100% specificity in comparison to FDA-licensed ELISA and Western blot assays for detecting HIV antibody in autopsy serum specimens. We conclude that this rapid, simply performed assay is accurate and applicable for use in several testing situations, including autopsy rooms. PMID- 8355001 TI - Disappearance of soft tissue and the disarticulation of human remains from aqueous environments. AB - Human remains recovered from aquatic environments were scored for regional presence of soft tissue, exposure of bone, and loss of body parts to determine the general pattern of soft tissue loss and loss of body parts. Regions scored were: the cranium, mandible, neck, hands, forearms, upper arms, feet, legs, pelvic girdle, and trunk. Initial disappearance of soft tissue, resulting in exposure of underlying bones, occurred in areas thinly overlain by soft tissue beginning with the head, hands, and anterior lower legs. Disappearance of body parts followed the general sequence: bones of the hands and wrists, bones of the feet and ankles, and the mandible and cranium. The lower legs, forearms, and upper arms are the next units to separate from the body. Known postmortem intervals for remains analyzed ranged from weeks to years and could not reliably be estimated based on the condition of the body at the time of recovery. As parts drop away from a floating carcass in large or current-driven bodies of water, they are often separated from the major body unit. This complicates recovery. Knowledge of disarticulation sequences allows more informed assessment of skeletal element recoveries to be expected and assists in the interpretation of artifacts and events produced by different disarticulating environments. PMID- 8355002 TI - A computer program for the estimation of time of death. AB - In the 1960s Marshall and Hoare presented a "Standard Cooling Curve" based on their mathematical analyses on the postmortem cooling of bodies. Although fairly accurate under standard conditions, the "curve" or formula is based on the assumption that the ambience temperature is constant and that the temperature at death is known. Also, Marshall and Hoare's formula expresses the temperature as a function of time, and not vice versa, the latter being the problem most often encountered by forensic scientists. A simple BASIC program that enables solving of Marshall and Hoare's equation for the postmortem cooling of bodies is presented. It is proposed that by having a computer program that solves the equation, giving the length of the cooling period in response to a certain rectal temperature, and which allows easy comparison of multiple solutions, the uncertainties related to ambience temperature and temperature at death can be quantified, substantiating estimations of time of death. PMID- 8355003 TI - Infant death in San Francisco 1989-1990. AB - This paper examines all of the unexplained and violent deaths of children less than one year of age in the City and County of San Francisco during the years 1989-1990. A total of 62 cases were collected and analyzed retrospectively. Among the cases we examined, 34 deaths were determined as SIDS, while seven were moded as accidents and two as homicides. The deaths were examined with respect to the following parameters: sex, race, age, height and weight, cause and manner of death, significant autopsy and microscopic findings; circumstances of death including place, the person discovering or reporting the death, the presence of siblings or previous child death in the family and previous illness in the same child. A particular stress is given to the definition and diagnosis of SIDS, according to the international literature, and to the criteria adopted to distinguish SIDS cases from accidents and homicides. A review of both the American and European literature shows that most articles do not include comparisons of data from both the autopsy and the scene. Additionally there is little standardization in the investigation and the extent of postmortem examinations performed. An international standardization of these methods appears necessary and the use of protocols to assure complete investigation and postmortem examination will allow more intensive evaluation of data. Here we give a brief presentation of the necropsy protocol for Sudden Unexpected Infant Death recently written and approved by the California Department of Health Services and used in the Chief Medical Examiner's Office in San Francisco. PMID- 8355004 TI - Gang-related homicides in Los Angeles County. AB - The incidence of gang homicides in Los Angeles County has increased faster than that of non-gang homicides in the past decade. This study compares characteristics of gang homicide victims with those of non-gang homicide victims for the year 1987. In 1186 cases, gang members were more likely to be young Black men who died of gunshot wounds. Gang homicide victims were more likely to die of firearm injuries in the early evening, and were more likely to die in a relatively small area of Los Angeles County. Drive-by shooting was highly associated with gang homicide. PMID- 8355005 TI - A comparative study of erotomanic and obsessional subjects in a forensic sample. AB - Erotomania is the delusional belief that one is passionately loved by another. These persons often go to great lengths to approach their object of desire, often necessitating the attention of the law. We have reviewed a forensic sample to select subjects who meet criteria for the diagnosis of erotomania. Case histories from all of the case files of the Threat Management Unit of the Los Angeles Police Department were reviewed to compare erotomanic subjects with those who were suffering from other disorders. Various demographic and other relevant data were examined to determine if the erotomanic subjects presented similar or different profiles. PMID- 8355006 TI - Postmortem alcohol production in fatal aircraft accidents. AB - During 1989 and 1990, the Civil Aeromedical Institute received specimens from 975 victims of fatal aircraft accidents. The maximum concentration of ethanol allowed under FAA regulations (0.04%, 40 mg/dL) was exceeded in 79 of these cases (8%). It was determined based on the distribution of ethanol in urine, vitreous humor, blood, and tissue that 21 of the positive cases (27%) were from postmortem alcohol production. Twenty-two of the positive cases (28%) were found to be from the ingestion of ethanol. In 36 cases (45%), no determination could be made regarding the origin of the ethanol. In two cases, postmortem alcohol production exceeded 0.15% (150 mg/dL). The opinion held by some toxicologists that postmortem alcohol production can be inferred from the presence of acetaldehyde, acetone, butanol, and other volatiles was found to be incorrect. Several cases with postmortem ethanol had no other volatiles. Volatile compounds were found in several cases where no ethanol was present. In addition a case was found in which the relative ethanol concentrations in blood, bile, and vitreous humor were solely consistent with the ingestion of ethanol, but acetaldehyde, acetone, and 2 butanol were also found in blood. This clearly indicates that the presence or absence of other volatiles does not establish postmortem ethanol production. PMID- 8355007 TI - Improved long-term stability of blood cocaine in evacuated collection tubes. AB - A study was undertaken to determine if a relatively minor modification of our existing specimen collection tubes could enhance the long-term stability of blood cocaine. We added cocaine, benzoylecgonine (BE) and ethanol to whole sheep blood in glass tubes that were prepared to contain one of several combinations of preservatives and anticoagulant. On day 1 and at intervals of up to one year, the drugs were measured by gas chromatography-mass spectrometry (cocaine and BE) or headspace gas chromatography (ethanol). Storage of blood containing 200 ng/mL cocaine at 4 degrees C for one year resulted in 100% loss of the drug using our normal 10 mL specimen collection tubes containing 100 mg sodium fluoride and 20 mg potassium oxalate. The substitution of oxalic acid for potassium oxalate reduced this loss to 76% without any significant effect on the benzoylecgonine or ethanol concentrations. Further addition of 10 mg echothiophate iodide, a quaternary ammonium compound, brought the cocaine loss down to 60% of the original concentration by one year. Further work will be required to determine if oxalic acid and/or echothiophate iodide could be used in blood collection vials intended for forensic toxicological purposes without any detrimental effect on other assays. PMID- 8355008 TI - Observations of differential decomposition on sun exposed v. shaded pig carrion in coastal Washington State. AB - The decomposition of two pig carcasses in close proximity to each other, one exposed and the other shaded, in a continuous woodland were observed and different rates of decay were recorded. The exposed pig decomposed much faster than the shaded pig, reaching a stable minimal weight two weeks before the shaded carcass. Bloat size, body weight, occurrence of blow fly larvae, and ambient air temperatures are compared. Maggot development appeared to be a major factor in the overall rate of decomposition and was affected primarily by different temperature patterns at the two sites. PMID- 8355009 TI - Cholinesterase activity in postmortem blood as a screening test for organophosphate/chemical weapon exposure. AB - This study was undertaken to determine whether postmortem blood cholinesterase activity could be used as a screening test for exposure to nerve agents. Whole blood cholinesterase activity at 25 degrees C was analyzed for a one week period in order to simulate the battle field collection problems of: hemolyzed blood samples, delayed recovery of the specimen, and unrefrigerated transfer to the testing facility. A total of 53 nonpreserved post-mortem whole blood specimens were analyzed in triplicate for cholinesterase activity by the delta pH method of Michel. There was a negligible loss of cholinesterase activity by the seventh day of the study. The enzyme activities of the specimens had a mean value (range) of 0.48 (0.20 to 0.74) initially and 0.45 (0.07 to 0.70) pH units after one week. Whole blood from five healthy adults remained essentially unchanged during this period, with an initial value 0.59 (0.52 to 0.67) and a final value of 0.52 (0.46 to 0.62) pH units. To compare postmortem and simulated nerve agent values, aliquots from 18 of the original 53 postmortem specimens were frozen during day one of the study, thawed on day seven and a cholinesterase inhibitor added. These specimens were then analyzed with the other specimens. All values from inhibited specimens were essentially zero (0.0 to 0.01) pH units compared to a range of 0.07 to 0.61 pH units for matched, uninhibited, day seven postmortem specimens. Fifteen actual nonpreserved specimens from the battlefield were analyzed as verification of screen performance. Their results fell within the uninhibited postmortem range above.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355010 TI - ABO blood grouping on dental tissue. AB - Twenty-five permanent teeth, including eight carious ones whose pulp cavities had been exposed, were used for this research 3-5 weeks after extraction. Phosphate buffered saline (PBS, at pH 7.2) was employed to extract ABO blood group substance from tooth powder. ABO grouping was performed on blood-stained compresses from the extraction wound (as controls), tooth fragment, tooth powder, and cotton fibers immersed in PBS extract by absorption-elution (AE) technique and on the PBS extracts by the two-dimensional absorption-inhibition (2-D AI) technique. It was found that blood grouping in PBS extracts by 2-D AI yielded reliable results: no false positive results, and a high rate of correct grouping, (24/25), while blood grouping on other dental materials, such as tooth fragments, tooth powders, immersed fibers, by AE gave an unacceptable rate of false positive/negative results. PMID- 8355012 TI - Two deaths involving isoflurane abuse. AB - Two deaths due to isoflurane abuse are reported. One case was a suicide and the other a multiple drug death including isoflurane. A simple headspace gas chromatographic method was used for isoflurane quantitation. A review of the literature did not reveal blood and tissue concentrations of isoflurane. Drug tissue distributions and a discussion of the toxicological findings are presented. PMID- 8355011 TI - Identification of human DNA in complex biological samples using the Alu polymerase chain reaction. AB - Alu-Polymerase chain reaction (PCR) was used to amplify human DNA from complex mixed sources of DNA. Amplification of human DNA sequences by Alu-PCR could be accomplished in samples containing low concentrations of template in the presence of excess heterologous DNA sequences. Thus, sensitivity and specificity are maintained in complex DNA mixtures allowing positive identification of the presence of human DNA sequences by this technique. PMID- 8355013 TI - Transection of trachea due to improper application of automatic seat belt (submarine effect). AB - The seat belt has been a major contributor in minimizing injuries in automobile accidents. However, it often causes characteristic patterned injuries to the body relative to its application at the time of an accident. We report an unusual case of a driver who sustained a transection of the trachea due to the "submarine effect" from improper application of the seat belt. PMID- 8355014 TI - Sudden death due to ruptured hydatid cyst of the liver. AB - The cyst stage of Echinococcus granulosus is commonly located in the liver, which frequently results in a long symptomless period. We present a sudden death due to a freshly hemorrhagic hydatid cyst following blunt trauma to the liver in a 19 year-old boy. The possible mechanism was thought to be an anaphylactoid reaction to the leakage of the cyst fluid. PMID- 8355015 TI - A suicide by self-decapitation. PMID- 8355016 TI - Positive identification in a case of intentional extreme fragmentation. AB - The investigation of the first of the murders of young males to which Jeffrey Dahmer confessed led to systematic survey of two acres of semirural property in Bath Township, Ohio. The survey revealed the fragmentary skeleton of a young adult male, as well as bones of several species of animals. Through archaeobiological analysis, the animal bones were identified and taphonomic modifications documented. The human bones were dry and weathered, and many were rodent-gnawed, indicating that they had been exposed for many years. The human bones displayed an extreme degree of splintering, warping, bending, and spiral breakage. The only relatively complete bone was a cervical vertebra. Dismemberment and breakage had been accomplished by cutting, blunt force, and, in the case of the ribs, manual bending. Even in so extreme a case of intentional fragmentation, however, forensic anthropological analysis resulted in positive identification, with the primary criteria based on matching osteological features evident in premortem and postmortem radiographs of a cervical vertebra. PMID- 8355017 TI - Radiographic identification of human remains through deformities and anomalies of post-cranial bones: a report of two cases. AB - Human remains can be identified radiographically by anomalies and deformities of the post-cranial bones when there are no old fractures and the cranium and extremities are not available. These anomalies and deformities of the sternum, vertebrae, sacrum and innominate bone are often protected from damage by scavengers. We report their use to exclude a proposed identity in one case and to confirm identity in another case. The value and number of these criteria and their pathogenesis is discussed with reference to their prevalence and their expression of inter- and intraindividual variability. PMID- 8355018 TI - Nine-year follow-up study of a plasma-derived hepatitis B vaccine in a rural African setting. AB - One hundred and one of 255 recipients of a plasma-derived hepatitis B vaccine were evaluated in 1990, 9 years after the first vaccine dose in a study in Zambia to evaluate the efficacy of one, two, or three doses. In 1983, 2 years after the first vaccine dose, antibody to the hepatitis B surface antigen (anti-HBs) had been detectable in 90 of these 101 participants (89%). In 1990, anti-HBs was still detectable in 72 of 101 (71%), and was present at a protective level (> or = 10 mIU/mL) in 68 of 101 (67%). Although the original vaccine study elicited a protective level of antibody in a greater percentage of children and adolescents than in adults, there were no significant differences among the three groups at 9 years. (In 1990, anti-HBs was still detectable in 52 of 70 [74%] who had had no serologic markers of the hepatitis B virus in 1981, and a protective level was detected in 47 of 70 [67%].) A protective level of anti-HBs was detected in 1990 in 26 of 36 (72%) recipients of three doses and in 23 of 31 (74%) recipients of two doses; the slightly lower prevalence among recipients of one dose (19 of 34 [56%]) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355019 TI - Lassa virus activity in Guinea: distribution of human antiviral antibody defined using enzyme-linked immunosorbent assay with recombinant antigen. AB - More than 3,100 households in 27 selected villages distributed in the main geographic regions of Guinea were surveyed for the presence of Lassa virus specific IgG antibodies (LVA), using an enzyme-linked immunosorbent assay (ELISA) with Lassa virus nucleocapsid protein expressed in insect cells infected with a recombinant baculovirus as antigen. The highest prevalence of LVA (25-55%) was found among inhabitants of tropical secondary forest (areas near Gueckedou, Yomou, and Lola) and guinea savannah (Faranah and Kindia areas), near the southern frontiers with Sierra Leone and Liberia. A much lower prevalence (4-7%) was found among inhabitants of mountainous (Pita, Labe, and Mali) and coastal (Boffa, Boke) areas. We found no discernible differences in LVA prevalence between males and females or among various age groups. Testing of 406 hospital staff members of the eight central hospitals in these areas for LVA revealed a similar distribution of seropositivity among hospitals in various prefectures. The highest prevalence of LVA in hospital staff (29-40%) was in the Gueckedou and Lola hospitals. Sera of LVA-positive persons were tested via Western blot analysis. Antibodies bound predominantly to NP and GP2 proteins. PMID- 8355020 TI - Serological studies of an enterically transmitted non-A, non-B hepatitis in Somalia. AB - An outbreak of an acute sporadic viral hepatitis occurring at three villages in the lower Shebli region of southern Somalia was studied. Sera were examined for antibodies to hepatitis E virus (HEV) antigen by a recently developed enzyme linked immunosorbent assay. The prevalence of anti-HEV ranged from 77.8% to 94.0% among the three villages. Anti-HEV prevalence did not differ significantly with age or sex. HEV infections were widely distributed among all age groups, without a preponderance in any specific age category. Overall, 97.6% of afflicted patients who were examined 6-10 days after onset of jaundice developed either IgM or IgG anti-HEV. PMID- 8355021 TI - Human parvovirus B19 infections: routine diagnosis by a new nested polymerase chain reaction assay. AB - A nested primer PCR assay was developed to detect human parvovirus B19 in various clinical specimens in a routine diagnostic laboratory. Under optimized conditions the highly specific assay had a sensitivity of less than 10 genome units. For practical reasons, however, this sensitivity was adjusted to 10-100 virus genomes in diagnostic applications. Using clinical specimens from 200 patients with suspected B19 infection, nested PCR was shown to have important diagnostic advantages over the detection of B19 specific antibodies. The data suggest that on the basis of serological data as obtained with currently available test systems a considerable proportion of B19 infections would be misdiagnosed. Examples for the usefulness of the PCR assay in routine diagnosis are given. PMID- 8355022 TI - Detection of measles, mumps, and rubella antibodies in saliva using antibody capture radioimmunoassay. AB - Antibody capture radioimmunoassays were developed for detecting virus specific IgM (MACRIA) and IgG (GACRIA) to measles, mumps, and rubella and used to investigate saliva as an alternative specimen to serum for diagnosis. Saliva was collected from 63 patients with measles, 19 with mumps, and 150 with rubella, which were all clinically diagnosed and serologically confirmed. Virus specific IgM was detected in 92% of measles, 75% of mumps, and 100% of rubella saliva samples collected during the first week of illness. Between 1 and 5 weeks after onset virus specific IgM was detected in 100% of saliva specimens. After the 5th week the proportion of reactive specimens declined. The specificity of the MACRIA tests was established by testing saliva samples collected from blood donors for measles (88), mumps (88), and rubella IgM (91). All of the saliva specimens tested for measles and rubella specific IgM were unreactive, 1/88 specimens tested for mumps specific IgM contained significant reactivity. Saliva specimens collected from acute cases of MMR were tested in all 3 MACRIAs. A small proportion of saliva samples contained detectable IgM of more than one virus infection. Rubella and measles specific IgG was detected in the saliva of all cases from the 4th or 5th day of illness, respectively. Detection of mumps specific IgG was less successful. We have demonstrated that virus specific IgM can be reliably detected in saliva samples collected from acute cases of measles, mumps, and rubella and identified 1-5 weeks after onset of illness as the optimum time for collection of samples. PMID- 8355023 TI - Inflammatory myopathies. A review. PMID- 8355024 TI - Microvascular and neuronal consequences of common carotid artery thrombosis and platelet embolization in rats. AB - The microvascular and neuronal consequences of nonocclusive common carotid artery (CCA) thrombosis were documented in rats. Thrombosis of the CCA was produced by a rose bengal-mediated photochemical insult and regional patterns of blood-brain barrier (BBB) disruption were documented by horseradish peroxidase (HRP) histochemistry at 15 min (n = 12), 4 h (n = 3), 1 day (n = 5) or 7 days (n = 5) after vascular injury. At 15 min and 4 h after thrombosis, multiple foci of BBB disruption were present throughout the thrombosed hemisphere; protein leakage was occasionally detected contralaterally. Extravasated HRP was associated with well perfused arterioles and arterioles containing luminal platelet aggregates at different stages of degranulation. Evidence for local platelet adhesion and aggregation or endothelial disruption at these sites was not detected. However, HRP-containing endothelial plasmalemmal vesicles were present at leaky sites. Variable degrees of parenchymal injury were documented including dendritic and astrocytic swelling with neuronal necrosis. By 1 day after CCA thrombosis, the overall frequency of permeable sites, more commonly associated with luminal leukocytes and parenchymal necrosis, was reduced. At 7 days, vessels permeable to HRP were associated with tissue necrosis, reactive astrocytes and microglial infiltration. Arteriole wall thickening and leukocyte accumulation within arterioles and venules were also detected. Widespread platelet embolization leading to variable degrees of BBB disruption and tissue injury occurs after CCA thrombosis. Acute abnormalities in vascular permeability are thus hypothesized to play an important role in the acute pathogenesis of cerebrovascular thrombosis. Delayed leukocyte accumulation in this model of embolic infarction may represent a secondary insult to the injured brain. PMID- 8355025 TI - Ultrastructural morphometric features of human sural nerve endoneurial microvessels. AB - We studied the morphometric features of 366 transversely sectioned endoneurial microvessels in sural nerves from 50 healthy volunteers (mean age 34.5 +/- 15.8, range 20 to 66 years). Nerves were obtained and processed by the same techniques and standards used to study biopsied nerves from patients with neuropathy. Endothelial area, basement membrane area, number of endothelial nuclei and junctions, and number of periendothelial nuclei all increase significantly with vessel size as judged by mural area. Periendothelial cell coverage of endothelial perimeter does not correlate with vessel size. Components of endoneurial microvessels, specifically the area containing basement membrane, do not change significantly with age. The present report provides a detailed characterization of the ultrastructural features of endoneurial microvessels with age in humans and provides optimal reference values for study of microvessel pathologic changes in disease. PMID- 8355026 TI - X-ray-induced cell death in the developing hippocampal complex involves neurons and requires protein synthesis. AB - Sprague-Dawley rats aged 1 or 15 days were irradiated with a single dose of 200 cGy X-rays and killed at different intervals from 3 to 48 hours (h). Dying cells were recognized by their shrunken and often fragmented nuclei and less damaged cytoplasm in the early stages. On the basis of immunocytochemical markers, dying cells probably represented a heterogeneous population which included neurons and immature cells. In rats aged 1 day the number of dying cells rapidly increased in the hippocampal complex with peak values 6 h after irradiation. This was followed by a gentle decrease to reach normal values 48 h after irradiation. The most severely affected regions were the subplate and the cellular layer of the subiculum, gyrus dentatus and hilus, and the stratum oriens and pyramidale of the hippocampus (CA1 more affected than CA2, and this more affected than CA3). X-ray induced cell death was abolished with an injection of cycloheximide (2 micrograms/g i.p.) given at the time of irradiation. X-ray-induced cell death was not changed after the intraventricular administration of nerve growth factor (NGF; 10 micrograms in saline) at the time of irradiation. Cell death was not induced by X-irradiation in rats aged 15 days. These results indicate that X-ray induced cell death in the hippocampal complex of the developing rat is subjected to determinate temporal and regional patterns of vulnerability; it is an active process mediated by protein synthesis but probably not dependent on NGF. PMID- 8355027 TI - Muscle hypertrophy experimentally induced by administration of denervated muscle extract. AB - The effects of systemic administration of muscle extract on normal muscle were studied. Male Wistar rats received intraperitoneal injections of normal and denervated muscle extract over 5 consecutive days. Soleus muscles were then submitted to histological, histochemical and quantitative-morphometric analysis. The group receiving denervated muscle extract showed considerable muscle fiber hypertrophy, together with the formation of new fibers suggestive of hyperplasia. The systemic administration of denervated muscle extract was shown to have a considerable myotrophic effect on normal muscle, evident in the hypertrophy and hyperplasia of muscle fibers. PMID- 8355028 TI - A syndrome of acute severe muscle necrosis in intensive care unit patients. AB - Four septic patients and one asthmatic patient are described who developed a severe paralytic disorder in an intensive care unit (ICU), associated with a rise in serum creatine kinase and a severe necrotizing myopathy. All cases had received non-depolarizing muscle blocking agents and large intravenous doses of glucocorticoids. Three patients developed myoglobinuria. No improvement or very little improvement in muscle function was noted in the four fatal cases. The single survivor recovered his strength after 6 months. This syndrome ("necrotizing myopathy of intensive care") provides one of the differential diagnoses for ICU-acquired weakness. The myopathy appears to have several interdependent causes and it is proposed that these should be classified as myonecrosis "priming" factors (glucocorticoids, myotropic infections, sepsis) and "triggering" factors (non-depolarizing muscle blocking agents). PMID- 8355029 TI - Abnormal neuritic architecture identified by Di-I in Pick's disease. AB - The fluorescent stain Di-I combined with confocal microscopy identified an abnormal neuritic pattern in the cortices of frontal and anterior temporal lobes in postmortem tissues from patients with Pick's disease (PD). Focal, dense neuritic aggregates 50 to 200 microns in diameter were scattered throughout all cortical layers. The three-dimensional analysis provided by confocal microscopy revealed the neuritic clusters to consist of enlarged, randomly arrayed, dystrophic neurites that were not associated with amyloid deposits, astrocytic processes or capillaries. In the intervening neuropil, there were fewer neurites compared to controls. The occipital cortex, which is unaffected in PD, showed a neuritic architecture comparable to normal controls as did affected brain tissues from patients with Alzheimer's disease or remote, ischemic infarction. This neuritic pattern is, thus far, unique to PD and may reflect the loss of specific subpopulations of cortical neurons and proliferation of neurites of the remaining neurons. PMID- 8355030 TI - CD44 expression in human astrocytes and oligodendrocytes in culture. AB - CD44 is a glycoprotein present on the surface of some lymphocyte cell populations and other non-lymphoid cells, and is involved in many functions related to cell cell and cell-matrix interactions. In this study, expression of CD44 antigen in primary neural cell cultures derived from fetal and adult human brains was investigated. In cultures processed for double immunofluorescence staining, approximately 80% of fetal astrocytes and more than 95% of adult astrocytes expressed the CD44 antigen on the cell bodies and processes; CD44 was also detected in 50-60% of adult oligodendrocytes. Neurons in fetal brain cell cultures did not express CD44 at all. Western blot analysis performed in astrocyte- and in neuron-enriched cultures confirmed the results from immunostaining and showed that the antibody against CD44 reacted with a polypeptide, of approximately 80 kD, that is present exclusively in the astrocyte enriched cultures, but absent in neuron-enriched cultures. Our results indicate that CD44 glycoprotein is constitutively expressed in the human cells of glial cell lineage and its role is likely to be associated with normal neuroglia mediated adhesion/recognition processes. PMID- 8355031 TI - Immunocytochemical analysis of the cellular infiltrate in the spinal cord lesions in HTLV-I-associated myelopathy. AB - Immunocytochemical staining of spinal cords from five autopsied patients with HAM/TSP was performed using a panel of monoclonal antibodies reactive with T cells. T cell subsets, B cells, macrophages, natural killer cells, IL-2 receptor positive cells, and HLA-ABC and HLA-DR. In the spinal cords of patients with a shorter duration of illness, CD4+ cells, CD8+ cells and macrophages were evenly distributed in active-chronic inflammatory lesions. In striking contrast, we noted the predominance of CD8+ cells over CD4+ cells in the inactive-chronic inflammatory lesions of patients with longer duration of illness. Natural killer cells, IL-2 receptor-positive cells and B cells were only rarely present in both the active-chronic and inactive-chronic lesions. HLA-ABC was positive in endothelial cells and infiltrating mononuclear cells, and HLA-DR was positive in endothelial cells, microglia and infiltrating mononuclear cells. This study suggests that immune responses in the spinal cord lesions of HAM patients gradually change along with the duration of illness. PMID- 8355032 TI - Modulation of multidrug resistance: at the threshold. PMID- 8355033 TI - The clinical cancer researcher--still an embattled species. PMID- 8355034 TI - Persistence of circulating t(14;18)-positive cells in long-term remission after radiation therapy for localized-stage follicular lymphoma. AB - PURPOSE: To determine the prevalence of circulating t(14;18)-positive cells in patients with long-term remission after radiation therapy for stage I and II follicular lymphoma. PATIENTS AND METHODS: Peripheral-blood mononuclear cells from 21 patients in continuous remission were examined by a two-step polymerase chain reaction (PCR) assay for the detection of cells carrying a t(14;18) translocation with a breakpoint within the major breakpoint region (MBR) or minor cluster region (mcr). RESULTS: Follow-up duration was between 25 and 160 months, with a median of 6.5 years. Thirteen patients (62%) showed negative results on repetitive testing. Cells that were t(14;18)-positive were found in eight patients (38%), all carrying a breakpoint in the MBR. One patient relapsed in each group. CONCLUSION: Circulating t(14;18)-positive cells can persist in a high percentage of follicular lymphoma patients in long-term complete remission (CR) after radiation treatment for stage I and II disease. The significance of minimal residual t(14;18)-positive cells with regard to the risk of relapse needs to be investigated in further prospective long-term studies. PMID- 8355035 TI - Clinical activity of a cytotoxic fusion protein in the treatment of cutaneous T cell lymphoma. AB - PURPOSE: A phase I trial in patients with refractory hematologic malignancies was performed at our institution to test the clinical relevance of the selective cytotoxic activity of the interleukin-2 (IL-2)-diphtheria toxin fusion protein, DAB486IL-2. A subset of five patients from this trial, all with cutaneous T-cell lymphomas (CTCL), forms the basis of this report. PATIENTS AND METHODS: Two treatment schedules were used. One patient received DAB486IL-2 at a dose of 0.075 mg/kg/d intravenous (i.v.) bolus over 15 minutes daily for 5 consecutive days. The other four patients received DAB486IL-2 at a dose of 0.1 mg/kg as an i.v. infusion over 180 minutes weekly for 5 consecutive weeks. RESULTS: Three of the five CTCL patients achieved significant tumor responses. One patient attained a complete clinical and pathologic response (CR), which has been sustained without any interval treatment for 33+ months. Two other patients achieved partial responses (PRs) of 17+ and 4 months' duration, respectively. Treatment was well tolerated. The most common adverse effect was a transient increase in hepatic transaminases experienced by all five patients. CONCLUSION: The growth factor cytotoxin fusion protein DAB486IL-2 demonstrated significant clinical activity with acceptable toxicity in a group of heavily pretreated patients with CTCL. PMID- 8355036 TI - Novel oral combination chemotherapy in the treatment of intermediate-grade and high-grade AIDS-related non-Hodgkin's lymphoma. AB - PURPOSE: To determine the toxicity, response, and survival rate of orally administered combination chemotherapy in patients with AIDS-related intermediate- and high-grade non-Hodgkin's lymphoma. Secondary objectives included prospective quality-of-life assessment and quantitation of cell-associated p24 antigen (p24 Ag) by flow cytometry. PATIENTS AND METHODS: Eighteen patients with biopsy-proven lymphoma were treated with oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, etoposide 200 mg/m2 on days 1 through 3; cyclophosphamide 100 mg/m2 on days 22 through 31, and procarbazine 100 mg/m2 on days 22 through 31 at 6-week intervals. A variety of clinical assessments were performed: prospective quality-of-life assessment using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments; indirect immunofluorescence with flow cytometry to measure cell-associated p24 antigen; and price of the oral regimen compared with two other intravenous combination chemotherapy regimens. RESULTS: The overall objective response rate using Eastern Cooperative Oncology Group (ECOG) criteria was 61% (95% confidence interval, 39% to 84%), with seven complete remissions (39%) and four partial remissions (22%). The median survival duration was 7 months, with a range of 11 days to 36 months. The treatment related mortality rate was 11%. One patient developed CNS progression. Myelosuppression was the most frequent and severe toxicity encountered. Predictor variables of performance status (PS), prior history of thrush, and CD4 lymphocyte count were found to be of prognostic value. In a separate analysis, scores on the three subscales of the BSI were also found to be predictive of complete response. The price of this regimen is several thousand dollars less than that of other intravenous combination chemotherapy regimens. CONCLUSION: This regimen is active in patients with AIDS-related non-Hodgkin's lymphoma. Because it is important to design systemic cytotoxic chemotherapy regimens that are cost-effective, considerate of quality-of-life issues, and efficacious in this patient population, this approach should be compared with standard intravenous combination chemotherapy regimens in randomized controlled clinical trials. PMID- 8355037 TI - One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study. AB - PURPOSE: To determine if prolonged adjuvant treatment (2 years v 1 year) with combination chemotherapy (cyclophosphamide, methotrexate, fluorouracil [5-FU], vincristine, and prednisone [CMFVP]) in poor-prognosis breast cancer patients (estrogen receptor [ER]-negative, stage II to IIIA) would result in improved disease-free and overall survival rates. PATIENTS AND METHODS: Four hundred forty five women with ER-negative node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) over a period of 5 years (1979 to 1984). Randomized assignments were made to either 1 or 2 years of adjuvant CMFVP. Doses were daily oral cyclophosphamide 60 mg/m2, intravenous (i.v.) weekly methotrexate 15 mg/m2, i.v. weekly 5-FU 400 mg/m2, i.v. weekly vincristine .625 mg/m2 for the first 10 weeks, and prednisone weeks 1 through 6 with doses decreasing from 30 mg/m2 to 10 mg/m2. RESULTS: The median follow-up duration is 8.6 years, with a maximum of 11.3 years. Treatment arms were not significantly different as regards either survival or disease-free survival rates (P = .33 and P = .24, respectively). The five-year survival rate is 57% on the 1-year arm and 62% on the 2-year arm. Patients with three or fewer nodes and premenopausal status were associated with improved survival. Compliance on the 2-year arm was poor, with only 37% completing the full 2 years of treatment. SWOG grade 3 to 4 toxicity was experienced by 47% of patients on the 1-year arm and by 52% on the 2-year arm. There were no treatment-related deaths. CONCLUSION: We conclude that 2-year adjuvant treatment with CMFVP is not an improvement over 1-year treatment. Moreover, 2 years of CMFVP is difficult to complete. However, the results are not definitely negative. A moderate improvement attributed to prolonged chemotherapy, especially among patients with four or more positive nodes, cannot be ruled out. PMID- 8355038 TI - S-phase fraction is a prognostic factor in stage I breast carcinoma. AB - PURPOSE AND METHODS: The prognostic significance of cell proliferation, estimated as cytometric S-phase fraction (SPF), was investigated in node-negative breast cancer patients with small tumors (T1, NO). The 219 stage I patients originated from two series and were diagnosed either from 1978 to 1981 or from 1981 to 1985. The tumors were analyzed for estrogen receptors (ERs) by isoelectric focusing and for cellular DNA content by static cytofluorometry or flow cytometry. RESULTS: A high SPF correlated with the absence of ERs and abnormal DNA content, and was less often found in tumors smaller than 11 mm compared with those with a diameter between 11 and 20 mm. Among the variables age, tumor size, DNA ploidy, ER status, and SPF, only SPF showed a significant association with distant recurrence and breast cancer survival in systemically untreated patients. The relative recurrence rate for patients with an SPF of 10% or greater was three times that for patients with lower SPFs. Estimated 8-year breast cancer survival rates for the same groups were 72% and 91%, respectively. CONCLUSION: This study suggests that cytometric SPF has prognostic significance in stage I breast carcinoma. PMID- 8355039 TI - Assessment of estrogenic recruitment before chemotherapy in advanced breast cancer: a double-blind randomized study. European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group. AB - PURPOSE: In the present phase III study, the specific effect of estrogenic recruitment was assessed by comparing two groups of patients with advanced breast cancer receiving either ethinylestradiol (EE2) or placebo (PL) before chemotherapy (CT). PATIENTS AND METHODS: The therapeutic regimen consisted of (1) estrogen suppression by aminoglutethimide (AGL) 1 g/d plus hydrocortisone (HC) 40 mg/d, with surgical castration performed on premenopausal patients; (2) fluorouracil (5-FU) 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide (CPA) 500 mg/m2 (FAC) intravenously (IV) every 3 weeks; (3) following randomization, patients were double-blinded to receive either PL or EE2 50 micrograms exactly 24 hours before receiving FAC. All patients had advanced breast cancer presumably sensitive to endocrine therapy (estrogen receptor-positive [ER+] and/or progesterone receptor-positive [PgR+] status) with measurable lesions; none had received prior systemic antineoplastic therapy for metastatic disease; prior adjuvant hormonal therapy (HT) or CT (without anthracyclines) was allowed if interval since completion was longer than 1 year. RESULTS: Among 154 patients treated according to the protocol, tolerance, response rates, time to progression, and median survival duration were identical in the PL and EE2 groups. Only performance status, dominant metastatic site, and menopausal status seemed to influence response (overall response, 64%), with the highest levels of partial remission (PR) and complete remission (CR) being achieved in premenopausal women (CR plus PR, 26% plus 55%) and in those with dominant soft tissue lesions (CR plus PR, 45% plus 28%). CONCLUSION: We conclude that the validity of the hormonal recruitment concept has not yet been established in clinical practice so that this approach remains experimental. The results achieved by combining (near) complete estrogenic suppression and cyclical FAC chemotherapy are not significantly different from those to be expected with the more conventional use of HT followed by CT in presumably hormone-responsive (ER+) patients. PMID- 8355040 TI - Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. AB - PURPOSE: Hepatic venoocclusive disease (VOD) is a common complication of cytoreductive therapy for marrow transplantation. Only 25% of patients who develop VOD have severe disease. We tested the hypothesis that early clinical signs of VOD would predict which patients would recover and which would die. PATIENTS AND METHODS: We evaluated 355 consecutive patients who had transplants between August 6, 1987 and July 21, 1988 for occurrence of VOD and whether it was reversible within 100 days of transplant. Total serum bilirubin and weight gain from day -7 through day +16 posttransplant were compared among patients with no, severe, or nonsevere VOD. Logistic regression models were developed to estimate probabilities of severe VOD at each of six time intervals. The accuracy of these models was tested by applying them to 392 consecutive patients who underwent transplantation between July 22, 1988 and July 20, 1989. RESULTS: As early as day -1, bilirubin and weight gain were significantly different between patients whose VOD proved to be severe and patients with reversible VOD or no disease. Regression models were used to generate coefficients (beta 0, beta 1, beta 2) for the equation P = 1/(1 + e-z), where P is the probability of severe VOD and z = beta 0 + beta 1 (In total serum bilirubin [mg/dL]) + beta 2 (percent weight gain). Application of this equation to the next 392 patients allowed us to calculate sensitivity, specificity, and positive predictive value for a range of probabilities. CONCLUSION: The course of VOD after cytoreductive therapy can be predicted by knowing the serum bilirubin and weight gained within 1 to 2 weeks of transplantation. Probability estimates derived from patient data are highly specific and moderately sensitive. Such probability estimates may be useful when considering potentially risky interventions to treat VOD, such as recombinant human tissue plasminogen activator. PMID- 8355041 TI - Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma. AB - PURPOSE: To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. PATIENTS AND METHODS: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5 FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. RESULTS: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity. CONCLUSION: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1. PMID- 8355042 TI - Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early stage melanomas of the head and neck. AB - PURPOSE: We developed intraoperative lymphatic mapping with selective lymphadenectomy (SLND) to identify micrometastatic spread of cutaneous melanoma to regional lymph nodes. This study was undertaken to assess the sensitivity and specificity of our technique in patients with clinical stage I (CS-I) melanoma of the head or neck. PATIENTS AND METHODS: Seventy-two CS-I melanoma patients underwent intraoperative lymphatic mapping of primary cutaneous melanomas located on the head, neck, or upper chest/back draining to the neck. Key (sentinel) cervical lymph nodes in the regional lymphatic drainage basin were identified, selectively excised during SLND, and examined for microscopic evidence of tumor cells. If these sentinel nodes were tumor-negative, the surgery was concluded; if the sentinel nodes were tumor-positive, all nodes in the drainage basin were removed during en bloc lymphadenectomy (LND). RESULTS: Intraoperative lymphatic mapping identified sentinel nodes in 90% of the regional drainage basins. Fifteen percent of these nodes were tumor-positive, indicating the need for LND. There were no false-negative sentinel nodes, and extended follow-up showed no local nodal recurrences in patients whose sentinel-node histology did not indicate the need for LND. CONCLUSION: Intraoperative lymphatic mapping and SLND is a minimally invasive and highly accurate screening technique for determining which patients with CS-I head and neck melanomas have subclinical node metastases and therefore might benefit from cervical LND. PMID- 8355043 TI - Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities. AB - PURPOSE: To evaluate more accurately the effectiveness of preoperative chemotherapy in the treatment of patients with Ewing's sarcoma, we studied histopathologically the chemotherapeutic response and correlated it to oncologic outcome. PATIENTS AND METHODS: Between June 1983 and December 1989, 68 patients with nonmetastatic Ewing's sarcoma of the extremities were treated at our institute with preoperative chemotherapy (without radiation therapy) and surgery. The specimens were retrospectively evaluated for areas of viable tumor cells and graded from I to III (macroscopic, microscopic, or no residual disease, respectively) in a blinded fashion. Clinical follow-up data were available on all patients for a mean of 60 months (range, 32 to 111). RESULTS: This histopathologic analysis was strongly correlated with oncologic outcome (P = .004). Patients who demonstrated grade III response (no identifiable viable tumor nodules present) had improved 5-year disease-free survival rates as compared with patients with grade II (microscopic nodes present; P = .023; 90% v 53%) and grade I responses (macroscopic nodules present; P = .0003; 90% v 32%). Patients with grade II necrosis had statistically improved survival rates over those with grade I necrosis (53% v 32%; P = .074). CONCLUSION: This new histopathologic analysis technique for the evaluation of neoadjuvant chemotherapy effectiveness (which does not rely on tumor volume for its assessment) is a valuable prognostic indicator for patients with Ewing's sarcoma treated with surgery. Based on this preliminary report, cases of grade I or II chemotherapeutic tumor response should be considered clinical failures and a different, more aggressive postoperative chemotherapy regimen should be considered. PMID- 8355045 TI - Comparative pharmacokinetic studies of three asparaginase preparations. AB - PURPOSE: As part of pharmacologic studies of asparaginase (ASNase), we determined the half-life of ASNase activity and protein, and the effect of dose, repeated doses, different drug preparations, and hypersensitivity reactions on the half life (t1/2) of serum ASNase activity. PATIENTS AND METHODS: We measured ASNase activity (spectrophotometric assay) in serum samples obtained from patients with acute lymphoblastic leukemia (ALL) at various times during their therapy with intramuscular ASNase. ASNase protein was measured by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: Studies following the initial dose of Escherichia coli-derived ASNase demonstrated no difference in apparent t1/2 following 25,000 IU/m2 versus 2,500 IU/m2 (1.24 v 1.35 days, P = .2). The apparent t1/2s following maintenance doses of E coli ASNase (middle dose t1/2, 1.28 days, or last dose t1/2, 1.14 days) showed no difference when compared with the initial dose of ASNase (P = .3 to .9). There was no significant difference between the apparent t1/2s of ASNase activity and ASNase protein (n = 8, P = .2 to .6). The serum t1/2 was 0.65 and 5.73 days for patients receiving Erwinia or polyethylene glycol (PEG)-modified E coli ASNase, respectively, as the induction dose. ASNase activity was undetectable in sera of four patients studied in the week following an anaphylactic reaction to E coli ASNase and the t1/2 was significantly shorter in five patients with a history of allergic reaction to E coli ASNase who were studied following a dose of PEG ASNase, (t1/2, 1.80 days). CONCLUSION: We conclude that (1) the apparent t1/2 of ASNase is dependent on enzyme preparation used, but is not affected by dose or by repeated use; (2) the apparent t1/2 of E coli ASNase as a protein is the same as the apparent t1/2 of enzymatic activity; and (3) patients who have had a hypersensitivity reaction to E coli ASNase have a decreased apparent t1/2 with both E coli and PEG ASNase. PMID- 8355044 TI - Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma. AB - PURPOSE: To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS: Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS: Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5 year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION: In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor. PMID- 8355046 TI - Phase I clinical trial of carboplatin and 41.8 degrees C whole-body hyperthermia in cancer patients. AB - PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes in a phase I clinical trial. PATIENTS AND METHODS: Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m2. Carboplatin was administered at target temperature. RESULTS: Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung--minor response (200 mg/m2); gastrointestinal neuroendocrine--complete response (CR) (400 mg/m2); pancreatic- partial response (PR) (480 mg/m2); small bowel--PR (575 mg/m2); ovarian--CR, two patients (575 mg/m2), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2). CONCLUSION: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies. PMID- 8355047 TI - Subcutaneous interleukin-2 plus interferon alfa-2a in metastatic renal cancer: an outpatient multicenter trial. AB - PURPOSE: A prospective multicenter phase II trial was undertaken to define the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon alfa-2a (IFN) in patients with metastatic renal cancer. PATIENTS AND METHODS: Between December 1990 and October 1991, 42 patients with metastatic renal cancer who had received no prior immunotherapy were treated with IL-2 (4 x 10(6) U) days 1 through 4 and IFN (9 x 10(6) U) day 1 and 4 each week of a 4-week treatment course followed by a 2-week rest period. Maximum duration of therapy was 1 year. Concomitant therapy with acetaminophen, diphenhydramine, and indomethacin was recommended. Treatment was administered on an outpatient basis. RESULTS: With a median follow-up duration of 18 months, responses occurred in five of 42 patients (12%; 95% confidence interval [Cl], 2% to 22%). One pathologic complete remission, one surgical complete remission, and three partial remissions occurred. Toxicity was modest, with a symptom complex of rash, fever, anorexia, fatigue, mild weight loss, lymphocytosis, and eosinophilia occurring in 85% to 90% of patients. Renal dysfunction (creatinine > 2 mg/dL) occurred in 19% of patients, while three patients (7%) refused further IL-2 and IFN. No toxic deaths occurred. The median survival duration was 14.5 months. CONCLUSION: This outpatient low-dose subcutaneous regimen induced mild toxicity, a modest response rate, and an excellent median survival duration in previously untreated patients. Phase III trials are now needed to compare IL-2 plus IFN with IL-2 alone or to various IL-2/IFN regimens. However, the major task is to identify unique new agents with activity in renal cancer. PMID- 8355048 TI - Does interleukin-2 have a role in the management of acute leukemia? AB - PURPOSE: To discuss the possibility that interleukin-2 (IL-2)-based immunotherapeutic protocols may have a role in the management of acute leukemia. DESIGN: The preclinical results that have led to the clinical use of IL-2 in acute leukemia will be reviewed. The clinical data obtained with the administration of IL-2 to acute leukemia patients in different phases of their disease will be discussed, together with the clinicohematologic and immunologic modifications induced following the infusion of IL-2. Finally, the possibility that limitations associated with the exogenous administration of high-dose IL-2 may be circumvented by engineering techniques aimed at inserting the IL-2 gene directly into the tumor cells, will be addressed. RESULTS: The data indicate that high-dose IL-2 may be administered to acute leukemia patients. Toxicity, recorded in all patients, appears to be controllable using a continuous intravenous (i.v.) infusion protocol based on a daily dose-escalating administration. Complete remissions have been documented in acute myeloid leukemias (AMLs) with a limited, but detectable proportion of residual marrow blasts. Numerous phenotypic and functional changes have been recorded within the immune system of the host. Using retroviral vectors, the IL-2 gene may be productively transduced into human acute leukemia cell lines. CONCLUSION: IL-2 appears to represent a therapeutic option for AML patients with limited/minimal residual disease. The results of the ongoing randomized trials in patients in first or second remission are awaited. PMID- 8355049 TI - Intravenous mercaptopurine: life begins at 40. AB - PURPOSE: This review is intended to provide a concise portrayal of the background, rationale, and current use of intravenous infusions of mercaptopurine (6MP) in patients with acute leukemia. DESIGN: After a brief description of the mode of action of 6MP and the formulation, pharmacokinetics, and history of its intravenous administration, the rationale for current use of intravenous 6MP infusion is explained. Subsequently, the review summarizes and discusses clinical experience with intravenous 6MP alone and in combination with intravenous methotrexate (Mtx) and cytarabine (Ara-C). RESULTS: Although still an investigative drug, intravenous 6MP has been used for 40 years and currently is being administered extensively to children with previously untreated acute lymphoid leukemia (ALL) in frontline protocol studies. The reasons are the better and more consistent bioavailability of intravenous versus oral MP, higher blood and CSF levels, compliance, and preliminary evidence suggesting superior remission experience for intravenous Mtx and 6MP than for Mtx alone. The apparent lack of late adverse sequelae with 6MP as compared with other antileukemia drugs adds to this interest. CONCLUSION: The new life of intravenous 6MP at age 40 years illustrates the need for continued investigation of significant anticancer drugs as insights and technology progress. PMID- 8355050 TI - High-dose melphalan is not associated with extramedullary relapses in high-risk multiple myeloma. PMID- 8355051 TI - More on follicular lymphomas. PMID- 8355052 TI - Adoptively transferred anti-CD3-activated T cells for human tumor immunotherapy. PMID- 8355053 TI - Palindromic baldness: cytotoxic drugs correct alopecia. PMID- 8355054 TI - Physician advocacy deficit. PMID- 8355055 TI - Scintimetric evaluation of remodeling after bone fractures in man. AB - In a review of bone scans of 2000 post-trauma patients, the following rules of bone remodeling after fracture were found: different bones behave differently; lesions in the vicinity of joints show an early and high accumulation of the tracer within the first days after the trauma, whereas fractures of the axial skeleton and shafts of long bones sometimes need up to 12 days to appear on scan; all except skull fractures demonstrate a steady rise of accumulation intensity compared to normal bone for 2-5 wk; the steepness of increase and time of maximum differ significantly for different fracture sites. Calculating a ratio 24:4 hours after injection helps differentiate fractures from soft tissue lesions since fresh fractures show a ratio > 1:1. We found no clinically relevant dependence on sex and age. The scintigraphic/scintimetric behavior of fractures is reproducible and predictable, adding specificity to the well-known high sensitivity of bone scans. PMID- 8355056 TI - Diagnosis of partial and total physeal arrest by bone single-photon emission computed tomography. AB - Bone single-photon emission computed tomography (SPECT), capable of creating maps of the distribution of osteoblastic activity in every spatial plane of a physis, should provide images of diagnostic value in the case of patients suffering from growth arrests (epiphysiodeses). Seventy-five bone SPECT scans were obtained in 64 children suspected to have developed physeal arrests. The transaxial slices of the physis, in the case of partial epiphysiodeses: (a) indicated the percentage of the remaining normal physis, (b) located the bony bridge within the physis and (c) showed the slowdown of the growth of the remaining normal physis induced by the bony bridge in some children. Misdiagnosis occurred in six patients. For total epiphysiodeses, the radionuclide diagnosis was confirmed in 20 of 21 patients. Radionuclide, x-ray and MRI examinations in the study of growth disturbances were found to be complementary. PMID- 8355057 TI - Quantitative analysis of the technetium-99m-DTPA captopril renogram: contribution of washout parameters to the diagnosis of renal artery stenosis. AB - Retrospective analysis of precaptopril and postcaptopril DTPA renograms from 88 hypertensive patients was performed to refine the quantitative criteria used to diagnose renal artery stenosis (RAS). Of the 88 patients, 45 had RAS and 43 had normal renal arteries at angiography. Using time-activity curves from the essential hypertensive group, diagnostic washout criteria for a positive DTPA renogram were developed. These were based on the 20 and 30 min/peak activity ratios in each kidney. When the washout criteria were retrospectively applied to patient data as a whole, sensitivity and specificity for RAS were 67% and 79%, respectively. When previously described uptake criteria, based on the time to peak activity in each kidney and the GFR ratio between the kidneys, were applied to the same data, sensitivity and specificity for RAS were 89% and 84%, respectively. Quantitative analysis of the DTPA renogram using the time to peak and GFR ratio was both sensitive and specific for RAS. Measurement of 20 and 30 min/peak renal activity ratios did not improve the accuracy of the test. PMID- 8355058 TI - Initial assessment of positron emission tomography using 2-fluorine-18-fluoro-2 deoxy-D-glucose in the imaging of malignant melanoma. AB - To assess the feasibility and accuracy of positron emission tomography (PET) in the detection of metastatic malignant melanoma, the authors studied 12 patients approximately 1 hr following a 10-mCi injection of 2-[18F]-fluoro-2-deoxy-D glucose (FDG). Scan findings were compared to physical examination, imaging and biopsy results. For intra-abdominal visceral and lymph node metastases, the sensitivity of FDG-PET was 100% (15/15). PET also identified three metastatic foci noted only retrospectively on CT, and two metastatic foci seen only on follow-up CT several months later. Eight additional intense foci of FDG uptake that were seen on PET have not yet been confirmed as tumors. In superficial lymph nodes, PET correctly identified seven of seven metastatic lesions (including three cases involving normal-sized lymph nodes) and correctly predicted the absence of tumor in six of six lymph node regions, for an overall accuracy of 100% (13/13). The sensitivity of the PET technique for detecting small pulmonary lesions was lower than CT but this could be due to respiratory motion or prior cancer treatment. This initial experience demonstrates the feasibility and clinical potential of FDG-PET for the detection of regional and systemically metastatic malignant melanoma, particularly in extra-pulmonary lesions. PMID- 8355059 TI - Technetium-99m-HMPAO-labeled leukocytes and technetium-99m-labeled human polyclonal immunoglobulin G in diagnosis of focal purulent disease. AB - To evaluate the usefulness of 99mTc-HMPAO-labeled leukocytes and 99mTc-labeled polyclonal human immunoglobulin G (Technescan HIG) in the diagnosis of focal purulent disease, 31 comparative scintigraphies were done in 30 patients with known or strongly suspected focal infection. Focal purulent disease was the final diagnosis in 19 patients. Technetium-99m-labeled leukocytes showed 16 true positive, no false-positive, 11 true-negative and 3 false-negative findings. The corresponding figures for 99mTc-labeled HIG were 11, 2, 9 and 8. The sensitivity and specificity of imaging with labeled leukocytes were 84% and 100%, respectively, and with labeled HIG, 58% and 82%, respectively. The overall accuracy of the leukocyte scan was significantly better than that of the HIG scan (90% versus 67%, p < 0.001). Thus, if focal infection is suspected, scintigraphy with 99mTc-labeled leukocytes is the preferable method. No cases exhibited a better imaging result with 99mTc-HIG scintigraphy than with 99mTc-labeled leukocytes. PMID- 8355060 TI - Lymphoscintigraphy in high-risk melanoma of the trunk: predicting draining node groups, defining lymphatic channels and locating the sentinel node. AB - Lymphoscintigraphy was performed in 209 patients with high-risk melanoma of the trunk referred to the Sydney Melanoma Unit and considered for lymph node dissection. Lymphoscintigraphy accurately defined the draining lymph node groups and was 94% sensitive in detecting draining sites that contained metastases. When combined with the clinical finding of palpable lymph nodes, the sensitivity rose to 98%. Most patients showed lymph drainage to one or two node groups and only 22 patients showed drainage to 3 or more node groups. The major lymph channels could also be marked on the skin prior to incontinuity dissection. Most patients had multiple draining lymph channels and these often diverged significantly from each other in the path to the draining node group. The number and location of interval nodes could be determined and marked on the skin. These and the major lymph channels could thus be excised at the time of surgery. Unusual drainage patterns were sometimes seen; for example, three patients displayed a new lymph pathway with direct drainage from the back anteriorly to the para-aortic nodes. The location of the sentinel nodes in each draining lymph-node group could also be marked on the skin prior to surgery, enabling quick and accurate identification of this node, using the blue-dye technique if biopsy were to be performed. These findings lead us to recommend lymphoscintigraphy prior to wide local excision in patients with truncal melanoma who are candidates for surgery. Lymphoscintigraphy results will help plan surgery and lead to minimum surgical intervention, consistent with effective surgical management. PMID- 8355061 TI - Evaluation of pulmonary systemic blood flow using ECG gated acquisition. AB - We propose a functional parametric analysis method using ECG-gated 99mTc-labeled red blood cell (RBC) imaging for detection and characterization of periodic variations in local blood activity in the lungs during cardiac cycle. We validated in animal experiments that such count variations correlate with cyclical pulmonary blood flow and may be used for evaluation of systemic-to pulmonary shunts. Clinical studies were performed in 48 patients. After labeling the RBC pool with 99mTc, ECG-gated gamma camera images of both lung fields were acquired and processed to obtain Fourier transforms of time/activity functions in selected regions. The first harmonic parametric images of amplitude and phase were derived. There was an excellent correlation (r = 0.92) between activity variations and pulsatile flow measured by our method with that obtained by the thermodilution method in dog experiments (n = 10) after implantation of a systemic-to-pulmonary shunt. Patient studies showed the technique to be sensitive in detecting and quantifying abnormal systemic-to-pulmonary blood flow. Lung pulsatile flow can thus be noninvasively measured from functional parametric phase and amplitude images; the technique may be useful for detecting and quantifying abnormal systemic-to-pulmonary blood flow in man. PMID- 8355062 TI - SPECT in patients with cortical visual loss. AB - Single-photon emission computed tomography (SPECT) with 99mTc hexamethylpropyleneamine oxime (HMPAO) was used to investigate changes in cerebral blood flow in seven patients with cortical visual impairment. Traumatic brain injury (TBI) was the cause of cortical damage in two patients, cerebral ischemia in two patients and carbon monoxide (CO) poisoning, status epilepticus and Alzheimer's Disease (AD) each in three separate patients. The SPECT scans of the seven patients were compared to T2-weighted magnetic resonance image (MRI) scans of the brain to determine the correlation between functional and anatomical findings. In six of the seven patients, the qualitative interpretation of the SPECT studies supported the clinical findings (i.e., the visual field defect) by revealing altered regional cerebral blood flow (rCBF) in the appropriate regions of the visual pathway. MR scans in all of the patients, on the other hand, were either normal or disclosed smaller lesions than those detected by SPECT. We conclude that SPECT may reveal altered rCBF in patients with cortical visual impairment of various etiologies, even when MRI studies are normal or nondiagnostic. PMID- 8355063 TI - Regional cerebral blood flow-SPECT in chronic alcoholism: relation to neuropsychological testing. AB - To determine the prevalence of central nervous system damage due to ethanol, we evaluated 40 asymptomatic chronic alcoholics and 20 age-matched controls. Studies included neuropsychological testing, brain 99mTc-HMPAO SPECT, and morphometric analysis by CT scan. In the qualitative analysis, 30 of the 40 alcoholics showed hypoperfused areas on SPECT scan. In the semiquantitative analysis, alcoholics exhibited significant reduction in regional cerebral blood flow (rCBF) ratio of all brain lobes compared to controls (p < 0.001). The rCBF ratio was mainly reduced in frontal lobes (65%). Only 11 alcoholics showed significant frontal lobe atrophy in the morphometric analysis; most also had abnormalities on SPECT scan. Alcoholics exhibited significant impairment of frontal tasks and visuospatial skills. Frontal test impairment was independently related to both frontal atrophy and hypoperfusion. In a group of ten alcoholics in whom another SPECT scan was performed after 2 mo of ethanol abstinence, rCBF ratio of the frontal lobes normalized in eight, without frontal atrophy. In patients without frontal atrophy, reduced rCBF ratio of the anterior portion of the frontal lobes correlated negatively with frontal test results (r = -0.6535, p < 0.001). A significant negative correlation between cerebral perfusion and the amount of ethanol consumed in the month prior to study was observed (r = -0.6289, p < 0.001). In conclusion, asymptomatic chronic alcoholics frequently showed reversible frontal lobe hypoperfusion, which is related to recent ethanol intake, reflects brain function impairment and is independent of brain atrophy. PMID- 8355064 TI - Comparability of FDG PET studies in probable Alzheimer's disease. AB - Results of studies with positron emission tomography (PET) of 18F-2-fluoro-2 deoxy-D-glucose (FDG) in patients with probable Alzheimer's disease (AD) were compared among three European centers with different PET scanners (in-plane resolution ranging between 6.75 mm and 9.2 mm). A ratio of glucose metabolism in the most typically affected regions over the least typically affected regions was calculated to quantitatively analyze the characteristic pattern of AD. Diagnostic accuracy of this composite ratio was high (95.8%) and was superior to that of most ratios derived from single regions. Correspondingly, there was a consistent, highly significant difference between patients (mean ratio 0.77 +/- 0.11) and normals (mean 0.99 +/- 0.04) without significant differences among laboratories. Possible small effects of rate constant variation and region size were analyzed by computer simulation. The results demonstrate that a common investigation protocol may yield FDG PET data in different laboratories that are closely comparable in spite of differences between scanners and imaging equipment. PMID- 8355065 TI - Impact of antianginal medications, peak heart rate and stress level on the prognostic value of a normal exercise myocardial perfusion imaging study. AB - We sought to determine whether antianginal medications or the level of achieved stress affect the prognostic value of a normal exercise 201Tl study. We studied 261 patients with a normal exercise 201Tl study for 23 +/- 6 mo. Antianginal medications were taken at the time of stress testing in 128 patients. Peak heart rate ranged from 82 to 217 bpm; percent maximal predicted heart rate ranged from 42% to 136%. Chi-square analysis was used to determine the relationship of cardiac events to antianginal medications and stress indices. Primary cardiac events were defined as cardiac death or nonfatal myocardial infarction. Primary cardiac events occurred in six patients yielding an annual incidence of 1.2% per year. There was no significant relationship between cardiac event rate and antianginal medication use or any stress index, including Bruce stage, peak heart rate or blood pressure or percent maximal predicted heart rate achieved. The risk of cardiac death or nonfatal myocardial infarction in patients with a normal exercise 201Tl is low and is not affected by concurrent antianginal treatment or degree of stress achieved. PMID- 8355066 TI - Nitrates improve detection of ischemic but viable myocardium by thallium-201 reinjection SPECT. AB - Thallium-201 reinjection imaging improves myocardial viability detection when compared to standard 3-4-hr redistribution imaging, however, the extent of ischemic but viable myocardium is still underestimated. We tested whether the sensitivity of reinjection imaging could be increased by giving nitrates postexercise to improve blood flow during the redistribution period. Twenty patients with coronary artery disease were included, 11 of them with a recent myocardial infarction. All patients underwent two exercise/4-hr redistribution 201Tl SPECT protocols: one with reinjection alone and the other with nitrates and reinjection. In the latter case, 20 mg of Isosorbide Dinitrate were given to patients immediately after postexercise imaging. Fifteen patients had reversible defects with reinjection alone, three additional patients were defined as ischemic with nitrates/reinjection protocol. Reinjection alone identified 41 reversible segmental defects, all except one were also evaluated as reversible with nitrates/reinjection. However, among the 54 segments showing fixed defects after reinjection only, 14 (26%) presented as reversible with the nitrates/reinjection protocol. The redistribution extent (segments/patient) was 2.05 +/- 0.41 segments with reinjection alone and 2.75 +/- 0.38 (p < 0.01) with nitrates/reinjection. In 15 patients showing reversible defects with both protocols, the redistribution extent was 2.73 +/- 0.41 segments with reinjection alone and 3.20 +/- 0.40 (p < 0.05) with nitrates/reinjection. Thallium-201 SPECT with nitrates and reinjection improves the detection of ischemic but viable myocardium in comparison to SPECT with reinjection alone. PMID- 8355067 TI - Myocardial perfusion imaging and dynamic analysis with technetium-99m tetrofosmin. AB - Technetium-99m tetrofosmin is a new myocardial perfusion imaging agent that accumulates rapidly and shows slow clearance from the myocardium. Dynamic acquisition and SPECT imaging were performed in a total of 26 patients. Using exercise-rest protocol, the single-photon emission computed tomography (SPECT) findings of 130 myocardial segments were classified as infarction, ischemia and partial filling and compared to those with 201Tl. Complete concordance of findings was obtained in 108 segments (83%) between images with 99mTc tetrofosmin and 201Tl. Partial filling was observed in 24 segments with 201Tl and 14 segments with tetrofosmin, showing a greater number of ischemic regions in 201Tl. However, in comparison with coronary arteriography (n = 19), overall sensitivity and specificity for detecting coronary artery stenosis (> or = 75%) was 15 of 25 (0.60) and 27 of 32 (0.84), respectively, which did not differ significantly from those of 201Tl, which was 18 of 25 (0.72) and 27 of 32 (0.84), respectively. Graphic analysis that assumes unidirectional transfer of the tracer was applied to initial dynamic changes and uptake constant k and distribution volume V were computed. Multiple vessel disease and congestive heart failure showed a low perfusion index (k/V), and may be used in this type of tracer with unidirectional uptake. This preliminary study in the clinical trial showed the usefulness of 99mTc tetrofosmin as a myocardial perfusion imaging agent. PMID- 8355068 TI - Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera. AB - Technetium-99m-teboroxime is characterized by a high extraction fraction over a wide range of blood flow rates, rapid myocardial clearance and avid hepatic uptake. This study determined the imaging parameters and examined the clinical efficacy of a rapid back to back adenosine stress/rest teboroxime myocardial perfusion SPECT protocol using a triple-detector camera. Acquisition parameters were determined using cardiac phantom studies which were then applied in SPECT studies of 51 catheterized patients (22 with prior myocardial infarction) and 20 patients with a "low" (7.9% +/- 4.3%) likelihood of coronary artery disease. Technetium-99m-teboroxime (20-25 mCi) was injected at the third minute of adenosine infusion. Teboroxime (20-25 mCi) was also injected at rest, 15 min later. Stress followed by rest SPECT were completed within 25 min using a triple detector camera and sequential, 1-min continuous rotations in alternating directions. Summed raw data from the first to second (1-2 min), second to third (2-3 min) and second to fifth (2-5 min) minutes of imaging following stress teboroxime injection were reconstructed and compared for image quality, degree of liver interference, and accuracy for diagnostic efficacy. In a subgroup of 30 patients, 2-8-min summed images were also reconstructed to compare this more conventional imaging protocol with our rapid acquisition. Image quality was fair to good in 75% of the 1-2-min, 84% of the 2-3-min and 2-5-min studies and 53% of the 2-8-min scans. The frequency of severe liver interference appeared to increase with the duration of imaging time (1-2 min: 3%; 2-3 min: 7%; 2-5 min: 8%) and was greatest (30%, p = 0.08) with 2-8-min images. Three patients (4%) had uninterpretable studies due to intense hepatic uptake. Overall sensitivity (95%) and specificity (71%) were equal for the 2-3-min and 2-5-min stress images and appeared better than in the 1-2-min images (84% and 57%, respectively). For the 2 8-min scans, vessel sensitivity (69%) and specificity (63%) appeared poorer than with 2-3-min studies (83% and 81%, respectively). Normalcy rates were 89% for the 2-3-min and 2-5-min and 79% for 1-2-min images. The back to back adenosine stress/rest teboroxime SPECT can be performed in 30 min using a triple-detector camera. Although overall high sensitivity and normalcy rates were achieved, the protocol is technically demanding. Interference due to intense liver uptake remains problematic. PMID- 8355069 TI - Quantitative same-day rest-stress technetium-99m-sestamibi SPECT: definition and validation of stress normal limits and criteria for abnormality. AB - Gender-matched stress normal limits and criteria for abnormality for rest-stress 99mTc-sestamibi same-day myocardial perfusion imaging were developed and validated in 160 patients who were imaged using previously developed optimized acquisition, processing and quantitative protocols. The gender-matched mean and standard deviation of the normal response were calculated using 35 male and 25 female patients with a < 5% likelihood of coronary artery disease. Receiver operating curve analysis using expert visual interpretation as the "gold standard" was used to determine the optimal criteria for abnormality detection, in terms of standard deviations from the mean and minimum defect size for each of the four major zones of the polar map, in a pilot population consisting of an additional 35 male and 25 female patients with a variety of perfusion defects. The optimum standard deviations resulted in the following true-positive/true negative rates when quantitative results were compared to visual analysis for the anterior, septal, lateral, and inferior segments in the combined male and female pilot populations: 84%/86%, 70%/75%, 86%/76% and 69%/76%, respectively. The final criteria were then applied to a prospective population consisting of 33 male and 7 female patients. This analysis resulted in the following true-positive/true negative rates for overall perfusion abnormalities and abnormalities of the LAD, LCX and RCA vascular territories: 97%/67%, 94%/73%, 73%/90% and 72%/91%, respectively. The optimized 99mTc-sestamibi stress normal limits and criteria for abnormality correlate well with expert visual interpretation of stress myocardial perfusion defects. PMID- 8355070 TI - Detection of doxorubicin cardiotoxicity in patients with sarcomas by indium-111 antimyosin monoclonal antibody studies. AB - To assess myocardial cell damage due to doxorubicin cardiotoxicity, we prospectively studied 30 patients with sarcomas who were receiving chemotherapy, including doxorubicin. Sixteen patients were treated by continuous infusion over 72 hr and 14 patients were treated by bolus injection. Antimyosin studies and left ventricular ejection fraction (LVEF) measurements were performed before chemotherapy and at intermediate and maximal cumulative doses. Myocardial antimyosin uptake was quantified by a heart-to-lung ratio (HLR). Myocardial antimyosin uptake was observed in all patients at 240-300 mg/m2 when ejection fraction was still maintained. Seven patients presented with a decrease of > or = 10% in absolute ejection fraction units at 420-600 mg/m2. Five of these patients had mild congestive heart failure. All patients who presented with a decrease in LVEF > or = 10% at 420-600 mg/m2 had increased antimyosin uptake with HLR > or = 1.90 at a cumulative dose of 240-300 mg/m2. Patients who were treated with continuous infusion had less antimyosin uptake than those who were treated with bolus administration (mean HLR of 1.70 +/- 0.09 versus HLR of 2.01 +/- 0.16 at a cumulative dose of 240-300 mg/m2, p < 0.01; HLR of 1.86 +/- 0.12 versus HLR of 2.32 +/- 0.34 at a cumulative dose of 420-600 mg/m2, p < 0.01). Two of 16 patients treated by continuous infusion and 5 of 14 patients treated by bolus injection presented with a decrease in ejection fraction > or = 10%. LVEF after chemotherapy in the infusion group was 56% +/- 5% and 48% +/- 8% (p < 0.05) in the bolus group. Antimyosin studies are helpful in the assessment of doxorubicin cardiotoxicity. Intense antimyosin uptake at intermediate cumulative doses identifies patients at risk of cardiotoxicity before ejection fraction deteriorates. Patients with sarcomas treated by continuous infusion present with less antimyosin uptake than those treated with bolus injection, indicating less severe cardiotoxicity. PMID- 8355071 TI - Antimyosin positivity in doxorubicin cardiotoxicity: earlier than the conventional evidence. PMID- 8355072 TI - Teboroxime, sestamibi and thallium-201 as markers of myocardial hypoperfusion: comparison by quantitative dual-isotope autoradiography in rabbits. AB - The scintigraphic assessment of myocardial hypoperfusion depends on the ability of imaging agents to delineate flow disparities. Accordingly, we compared the differential uptake of teboroxime, sestamibi and 201Tl in normal and hypoperfused myocardium using quantitative dual isotope autoradiography. Rabbits with acute coronary occlusions (n = 29) received dual isotope injections of teboroxime 201Tl or sestamibi 201Tl or single isotope tracer injections. A group of sham-operated controls (n = 15) received teboroxime and/or 201Tl. Multiple 30-mu short axis slices were collected from each heart and mounted on x-ray film along with tissue standards to independently generate separate 99mTc and 201Tl autoradiographs. Teboroxime and sestamibi produced greater normal-to-defect activity contrast than 201Tl in each dual isotope heart (range 8.4-48.9 [teboroxime] versus 2.6-12.3 [201Tl], p < 0.02 and 4.5-10.4 [sestamibi] versus 3.6-7.3 [201Tl], p < 0.03). Similar profiles were obtained in the single isotope hearts. Teboroxime produced larger autoradiographic defects than 201Tl in the dual-isotope hearts [16.0% +/- 5.6% (teboroxime) versus 12.9% +/- 5.3% (201Tl) of the LV, p < 0.02]. We conclude that the 99mTc-based perfusion agents teboroxime and, to a lesser extent, sestamibi, delineate hypoperfused myocardium more clearly than 201Tl. Teboroxime detects the largest area of hypoperfusion and may provide the most accurate assessment of myocardium at risk. PMID- 8355073 TI - Measurement of myocardial blood flow by radiolabeled tracers. PMID- 8355074 TI - Load independence of early diastolic filling parameters in the anesthetized canine model. AB - To evaluate radionuclide diastolic filling indices during acute pharmacologic changes in ventricular loading, 11 atrially paced dogs underwent simultaneous micromanometer left atrial and left ventricular pressure measurements. During phenylephrine infusion, systolic blood pressure increased from 110 +/- 16 (s.d.) to 147 +/- 19 mmHg (p < 0.01), causing the atrioventricular gradient to increase from 5 +/- 2 to 8 +/- 5 mmHg (p < 0.03) with no change in the time constant of isovolumic relaxation (Tau). Absolute peak filling rate increased from 40 +/- 21 to 59 +/- 44 kcts/sec (p < 0.05), but there was no change in first-half filling fraction. During dobutamine infusion, Tau shortened from 43 +/- 13 msec to 33 +/- 5 msec (p < 0.01) and first-half filling fraction increased from 39% +/- 19% to 56% +/- 18% (p < 0.05), with no change in atrioventricular gradient or absolute peak filling rate. Absolute changes from baseline for the first-half filling fraction were inversely proportional to absolute changes in Tau (r = -0.76, p < 0.05). We conclude that the left ventricular absolute peak filling rate is a load dependent index of diastolic function. In contrast, the radionuclide first-half filling fraction is independent of loading conditions, but is sensitive to substantial alterations in the rate of left ventricular isovolumic myocardial relaxation. PMID- 8355075 TI - Myocardial substrate utilization and left ventricular function in adriamycin cardiomyopathy. AB - We evaluated alterations of substrate utilization in a rat model of adriamycin cardiomyopathy with deteriorating left ventricular function. Rats were treated with adriamycin (2 mg/kg), once a week for 6, 8, 9 and 10 wk. Fluorine-18-F deoxyglucose (18F-FDG) and 125I-beta-methyl-branched fatty acid (125I-BMIPP) were used as tracers of glucose and fatty acid metabolism and 99mTc-hexakis (2 methoxyisobutyl-isonitrile) (99mTc-MIBI) was used as a myocardial blood flow tracer. Left ventricular ejection fraction (LVEF) calculated from gated blood pool images was used as an indicator of cardiac function. LVEF was normal in the 6-wk group (78.0% +/- 4.8%), abruptly decreased in the 8-wk group (43.1% +/- 10.1%) and further deteriorated in the 9-wk group (27.6% +/- 13.4%). Accumulation of 18F-FDG (%kgID/g) in the hearts of adriamycin treated animals progressively decreased compared to controls (2.19% +/- 0.38%); 1.47% +/- 0.42% (p < 0.01) at 6 wk, 1.22% +/- 0.27% (p < 0.001) at 8 wk, 0.69% +/- 0.56% (p < 0.001) at 9 wk and 0.50% +/- 0.08% (p < 0.001) at 10 wk. This decrease occurred earlier than the deterioration in LVEF. Myocardial accumulation of 125I-BMIPP decreased in the advanced stages of adriamycin cardiomyopathy and was well correlated with the decrease in 18F-FDG accumulation. However, the decrease was less profound than for 18F-FDG; 53.7% +/- 9.8% versus 31.6% +/- 25.4% of control at 9 wk (p = NS), 49.5% +/- 15.3% versus 22.6% +/- 3.5% of control at 10 wk (p < 0.05). Accumulation of 99mTc-MIBI did not differ between controls and the adriamycin treated groups. There were no differences in blood glucose levels between controls and adriamycin treatment groups. Both glucose and fatty acid utilization are decreased in adriamycin-induced cardiomyopathy and these critical impairments in energy metabolism are associated with heart failure. Impaired myocardial glucose utilization measured with 18F-FDG may be a particularly sensitive marker of adriamycin cardiomyopathy. PMID- 8355076 TI - A distributed pharmacokinetic model of two-step imaging and treatment protocols: application to streptavidin-conjugated monoclonal antibodies and radiolabeled biotin. AB - Two-step imaging and treatment protocols involve injecting a suitably prepared monoclonal antibody that can bind both to a specific tumor antigen and to a second reagent which carries a drug or radionuclide. The second component is injected later, after the antibody has distributed throughout the target tumors and been largely cleared from the plasma and normal tissues. We introduce a mathematical model for the analysis of such protocols and apply it to the case of a streptavidinylated monoclonal antibody and radiolabeled biotin diffusing into small, prevascular, densely cellular nodules that represent either primary or metastatic tumors. We examine the distribution of streptavidinylated antibody and radiolabeled biotin within a tumor nodule and compare the two-step protocol to a one-step protocol using radiolabeled antibody. Our analysis predicts that (1) streptavidinylation reduces both the amount of antibody that distributes into the tumor nodule and the homogeneity of that distribution; (2) streptavidinylated antibody in the nodule can be saturated by initial plasma concentrations of free radiolabeled biotin substantially lower than the initial plasma concentration of free streptavidinylated antibody; (3) radiolabeled biotin diffuses rapidly, but binds so quickly that it will not penetrate deeply into the nodule if too low a dose is given. Hence, nonuniform localization of radiolabel may result from a "binding site barrier" to diffusion of either or both components; and (4) the two step protocol permits imaging sooner after injection of radiolabeled material than the one-step protocol and produces a higher exposure in tumor relative to plasma, even in the presence of antigen turnover. PMID- 8355077 TI - SIMS microscopy imaging of the intratumor biodistribution of metaiodobenzylguanidine in the human SK-N-SH neuroblastoma cell line xenografted into nude mice. AB - Microdosimetric evaluations of targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (MIBG) require precise assessment of the intracellular and intratumor distribution of the drug. We report the use of secondary ion mass spectrometry (SIMS) microscopy, a technique capable of mapping any chemical element within a biological specimen, to determine 127I-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of 127I-MIBG biodistribution were mapped within the tumor after in vivo administration of the drug and sample processing with cryotechniques (high-speed freezing and cryo-embedding), which prevent MIBG diffusion from original sites of uptake. We showed that the biodistribution of the tracer was highly nonuniform within the tumor. At the cellular level, most of the drug accumulated in the cytosol and perinuclear areas. In contrast, chemical sample processing provided not only a considerable loss in sensitivity due to passive diffusion of the drug in the organic solvents, but also artefactual images mainly due to MIBG redistribution onto the cell nuclei. Based on our findings in this SK-N-SH experimental tumor model, we suggest that MIBG should be attached to long-range emitters, in the hope of irradiating the many tumorous areas that remain carrier free. PMID- 8355078 TI - Paradoxical changes in iodine-131 scintigraphic findings in advanced follicular thyroid cancer. AB - We present the findings on iodine-131 (131I) scintigraphy, thallium-201 (201Tl) scintigraphy and quantitative thyroglobulin (QTG) estimation in two patients with follicular carcinoma of the thyroid with extensive metastases. The lesions were initially seen on 131I scintigraphs, but were not subsequently visualized with scanning doses of 131I (5 mCi), while retaining their ability to produce increasing amounts of thyroglobulin and take up 201Tl. Implications in choosing the appropriate diagnostic tests in the management of differentiated thyroid cancer are discussed. PMID- 8355079 TI - Fast transmission CT for determining attenuation maps using a collimated line source, rotatable air-copper-lead attenuators and fan-beam collimation. AB - We describe a technique using a line source and a rotatable air-copper-lead assembly to acquire gamma transmission computed tomographic (TCT) data for determining attenuation maps to compensate SPECT emission scans. The technique minimizes problems associated with discriminating 99mTc transmission and 201Tl emission photons and requires only a modest increase in total study time. A 99mTc line source and a stacked foil ("multislat") collimator are placed near the focal line of a fan-beam collimator (114 cm focal length) mounted on one detector of a triple-camera SPECT system. We acquired TCT data of plastic rod and anthropomorphic thorax phantoms to investigate the capability of the line source and rotatable air-copper-lead attenuators to determine attenuation maps. The data were acquired with and without 5.4 MBq (145 microCi) of 201Tl placed in the myocardial chamber of the thorax phantom. Phantoms also were scanned using a curved transmission slab source mounted to a parallel-hole collimator. Fan-beam TCT images have improved resolution compared with parallel-beam TCT images. Two patient scans also were performed to evaluate the clinical usefulness of fan-beam TCT. The rotatable air-copper-lead attenuator method eliminates contamination of emission data by transmission photons and reduces spill-over of emission data into the transmission energy window for some cases. Results show the feasibility of using fast, sequential or interlaced transmission scans of a line source within a rotatable air-copper-lead attenuator assembly to obtain accurate attenuation maps for SPECT attenuation compensation. PMID- 8355080 TI - Accuracy of registration of PET, SPECT and MR images of a brain phantom. AB - Accuracy of a surface-fitting algorithm for three-dimensional image registration of single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance (MR) images was tested using a three dimensional, water-fillable brain phantom. Multislice or volume image sets were acquired for each modality. Small fiducial markers were attached to assess accuracy of surface fitting and provide an alternate fitting technique. A maximum gradient technique was found to work well for SPECT and PET edge detection. Transformation parameters for translation, rotation and scaling were determined by surface fit to match each SPECT and PET scan with MR images. Using the markers, overall translation errors were found to be < 2 mm in each direction and rotational errors < 2 degrees in every case. Errors for specific internal regions were also determined to be < 2 mm for most regions, with only a few fits resulting in errors > 3 mm for some cortical regions. Results indicate surface fitting to be sufficiently accurate for visual comparison of registered images and for enhanced SPECT and PET region of interest (ROI) determination and image reconstruction. PMID- 8355081 TI - Left ventricular systolic and diastolic function measurements using an ambulatory radionuclide monitor: effects of different time averaging on accuracy. AB - The accuracy of an ambulatory radionuclide detector (VEST) for left ventricular systolic (ejection fraction, EF) and diastolic (peak filling rate, PFR) measurements was assessed at different time averaging of the nuclear and electrocardiographic data. Fifty-one patients, in a total of 67 studies, underwent equilibrium radionuclide angiography (RNA) immediately before a VEST study. VEST data were analyzed using single-beat analysis and different time averaging of 5, 10, 15, 30 and 60 sec. Agreement between VEST and RNA in estimating EF and PFR was evaluated by computing limits of agreement (LA). These were computed as 1.96 times the s.d. of the mean differences between the two methods, expressed in the same unit as EF and PFR. Differences between the two methods were plotted against their mean, allowing investigation of any possible relationship between measurement error and the true value (whose best estimate is the mean between the two methods). The entire statistical analysis was repeated at each different time averaging. LAs for EF measurement by VEST were -10.4:8.8 (single-beat analysis), -11.2:9.9 (5-sec averaging), -5.4:4.8 (10-sec averaging), -4.9:4.5 (15-sec averaging), -6.2:5.6 (30-sec averaging), -6.9:4.5 (60-sec averaging). Results indicate good agreement between VEST and RNA in measuring EF, at least for time averaging > or = 10 sec. LAs for PFR ranged from -0.6:0.6 (single beat) to -1.0:0.6 (60-sec averaging), which was considered a clinically acceptable agreement between VEST and RNA. No relationship between measurement error and true value was found either for EF and PFR. PMID- 8355082 TI - A scintigraphic sign for detection of right-to-left shunts. AB - We evaluated the usefulness of a new scintigraphic sign, a quantum mottling pattern, in diagnosing right-to-left shunt using 99mTc-MAA particles. The quantum mottling pattern is characterized by random distribution of discrete clumps of radioactivity that are more intense than the general body background. Forty-nine 99mTc-MAA scintigrams were analyzed retrospectively for presence of a quantum mottling pattern in extrapulmonary soft tissues and brain. This distinctive pattern was observed in every patient (18/18) in whom a right-to-left shunt was confirmed by nonscintigraphic means and was noted only in one patient in whom independent proof of a right-to-left shunt was not available. In contrast, application of conventional criteria yielded a true-positive interpretation for 15/18 patients with right-to-left shunts and a false-positive interpretation for another four patients. Presence of a quantum mottling pattern on 99mTc-MAA images appears to be a reliable aid for detecting a right-to-left shunt. Use of this sign is likely to improve accuracy of the scintigraphic test in patients with small shunts. PMID- 8355083 TI - Uptake of technetium-99m MDP in primary amyloidosis with a review of the mechanisms of soft tissue localization of bone seeking radiopharmaceuticals. PMID- 8355085 TI - Nuclear medicine: more than just medical imaging. PMID- 8355084 TI - Noninvasive real-time monitoring of renal function. PMID- 8355086 TI - Gallium-67 citrate in liquid gastric emptying scintigraphy. PMID- 8355087 TI - Low-level radioactive waste sites: still a political football. PMID- 8355088 TI - NRC proposed amendments: too little, too late? PMID- 8355089 TI - The future of nuclear medicine: autonomy or integration? PMID- 8355090 TI - Osseous guided tissue regeneration using a collagen barrier membrane. AB - The formation of mature, fibrous tissue in surgical osteotomy sites during the healing process can produce clinically undesirable results such as nonunion or encapsulation of alloplastic implants. The techniques of guided tissue regeneration have been used to ameliorate this problem by presenting a barrier to the invasion of fibrous tissue elements into the wound-site clot. The most frequently used barrier material, polytetrafluoroethylene is effective, but suffers the disadvantage of requiring surgical removal after clot organization is completed. A biocompatible, resorbable membrane that will effectively control the type of tissue that can invade and organize a clot would be advantageous, because it would not require surgical removal. In the present study, the efficacy of a collagen membrane to effect guided tissue regeneration in a rabbit zygomatic arch osteotomy model was tested. Complete, bilateral narrow (1 mm) or wide (5 mm) vertical osteotomies were created in eight adult New Zealand white male rabbits. On one side, the wound site was surrounded by a collagen barrier membrane prior to closure, while the other side was left uncovered (control side). Four animals were killed at 2 and 4 weeks postoperatively for gross radiologic and histologic examination of the wound site. The wide osteotomy sites without a barrier membrane showed invasion by fibroblasts resulting in fibrous nonunion, while the contralateral sides with the barrier membrane showed no fibrous tissue ingrowth and bony union by 4 weeks postoperatively. Although narrow wound sites without the barrier membrane showed fibrous tissue formation, the perimeter of the defects showed some new bone deposited at the periosteal surface, bridging the osteotomy site and producing osseous union.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355091 TI - Conduction velocity of the human inferior alveolar nerve: a preliminary report. AB - This preliminary report describes a technique to consistently record electrophysiological signals from the uninjured inferior alveolar nerves of human subjects. Bilateral recordings were obtained from 15 consecutive human volunteers. The mean conduction velocity was 67.6 m/s, with no differences shown for right or left sides or gender. Conduction velocity testing could offer a new objectivity in the clinical study of the inferior alveolar nerve, aiding in the documentation, diagnosis, management, and follow-up of the sometimes complex neural lesions that oral and maxillofacial surgeons routinely see. PMID- 8355092 TI - Retromolar trigone mass. PMID- 8355093 TI - Benign cementoblastoma: report of an unusual case and analysis of 14 additional cases. PMID- 8355094 TI - Dirofilaria tenuis infection of the oral mucosa and cheek. PMID- 8355095 TI - Congenital epulis: review of the literature and case report. PMID- 8355096 TI - Aggressive infantile fibromatosis: report of a case undergoing spontaneous regression. PMID- 8355097 TI - A simple appliance for controlling mandibular movement following segmental resection. PMID- 8355098 TI - A modified technique for the sagittal split osteotomy. PMID- 8355099 TI - Problems with the ABOMS certification process. American Board of Oral and Maxillofacial Surgery. PMID- 8355100 TI - Watching out for public safety. PMID- 8355101 TI - Management of midface fractures: fifty years later. AB - Much has changed in the 50 years since Dr Parker described the development of rapid means of transportation as a portent of an increase in maxillofacial trauma. Contemporary surgeons must concern themselves with a host of nonsurgical care issues that are an integral part of oral and maxillofacial surgery practice. Expectations related to the patient, government, insurance carrier, and hospital staff have created a new practice environment. Standards of care are high and surgeon and patient needs are more complex. Dramatically improved diagnostic capabilities, use of open surgical techniques, improved rigid fixation devices, advances in techniques of resuscitation, and more focused surgical training have markedly improved the care of the facial trauma patient. The midface remains the central focus of our gaze when we engage in interpersonal relationships. Developmental and acquired aberrations of this region are likely to be more obvious than lower face abnormalities and, therefore, perceived as more disfiguring. Complex midface trauma repair requires precise surgical technique, with little margin for error. When ideal results are not achieved, the common contributing factors are intercurrent serious injury, anatomic and wound repair considerations, and failure to execute fracture repair principles. Hard and soft tissue volume changes may further compromise midface fracture repair, irrespective of the quality of the surgical outcome. Despite the advances made in the last 50 years, there is still room for future progress. An interdisciplinary committee of surgeons treating facial trauma should convene to establish a classification system for midface fractures that would satisfy medical record keeping and coding requirements, and facilitate fair and consistent reimbursement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355102 TI - Treatment of mandibular angle fractures using two 2.4-mm dynamic compression plates. AB - Sixty-five consecutive patients with fractures of the mandibular angle were treated by open reduction and internal fixation using two dynamic compression plates placed through a transoral incision using transbuccal trochar instrumentation and 2.4-mm screws. In the first 20 cases, the screws were inserted without tapping the drill holes. In the remaining 45 cases, the drill holes were tapped. No patient was placed into postsurgical maxillomandibular fixation or training elastics. Overall, 21 fractures (32%) developed infections requiring secondary surgical intervention. The infection rate was higher in those fractures where the holes were not tapped (40%) than those cases when the holes were tapped (29%). Of the 21 fractures that required hardware removal, 9 fractures were healed and required no further treatment; 12 had no firm bony union and required postsurgical maxillomandibular fixation. Only one case resulted in a malunion with resulting malocclusion. The use of two dynamic compression plates was found to be relatively easy, but resulted in an unacceptable rate of infection. PMID- 8355103 TI - A quantitative computer-assisted analysis of disc displacement in patients with internal derangement using sagittal view magnetic resonance imaging. AB - Forty patients diagnosed clinically as having internal derangement of one or both temporomandibular joints underwent magnetic resonance imaging. Seventy-three films were obtained: 26 films from 13 patients with bilateral symptoms; 40 films from 20 patients with unilateral symptomatic joints; and seven films from only the symptomatic joint in the remaining seven patients. Disc positions were evaluated in all of these films, and also in 17 films obtained from 10 asymptomatic volunteers. A system for quantitative measurement of disc position relative to the condyle in the closed-mouth position was used in two ways: manually, with an operator locating reference points and measuring them; and computer-assisted, with a special program developed to locate and measure these points. There was no significant difference in the results produced by these two methods. Important findings of this study were as follows: 1) 35% of the joints in the asymptomatic volunteers were found to have moderately or severely displaced discs; 2) only 75% of the joints diagnosed clinically as having an internal derangement were found to have significant disc displacement, which suggests that the other 25% must have had a different pathologic basis for the symptoms; and 3) the contralateral disc in the unilateral patients was found to be displaced as often as the disc on the symptomatic side (75%). PMID- 8355104 TI - Clinical evaluation of antibiotic-supplemented bone allograft. AB - Antibiotic-supplemented bone allograft (ASBA) was originally developed for treatment of combat-acquired, avulsive defects of the oral and maxillofacial skeleton. Earlier findings in experimental wound models showed that ASBA resulted in significantly improved wound repair of infected osseous defects when compared with conventional treatment. In this study, ASBA was evaluated in paired, comparable, mandibular third molar sockets and compared with the findings following conventional surgical removal. The results of this assessment showed that wound healing was significantly improved with the use of ASBA. Evidence produced by this clinical evaluation of ASBA suggests its potential use for other surgical bone defects when grafting is precluded by the risk of infection as a result of contamination by oral flora. PMID- 8355105 TI - Reduction of postoperative facial swelling by low-dose methylprednisolone: an experimental study. AB - The effectiveness of a low-dose, preoperative regimen of methylprednisolone for the reduction of postoperative facial edema after impacted third molar surgery was evaluated using the facial plethysmograph. Eleven patients were given 16 mg methylprednisolone orally the evening before surgery, combined with 20 mg methylprednisolone intravenously immediately preoperatively, in a double blind, randomized, crossover study. Facial contour was measured preoperatively, and then on days 1, 2, 3, 4, and 7 postoperatively. The low dose of methylprednisolone reduced swelling by 42% at 24 hours and 34% at 48 hours postoperatively. By the third day the difference was only 19%, suggesting the need for either a sustained release formulation or a multiday course. Trismus or the need for analgesic medication were not affected by this dose of methylprednisolone. PMID- 8355106 TI - Effects of maxillomandibular fixation on respiration. AB - The effects of maxillomandibular fixation (MMF) on respiration were studied by measuring pulmonary function in 27 healthy volunteer subjects and in six post operative patients who underwent MMF after sagittal split ramus osteotomies. In addition, airflow resistance of the mouth was measured in seven healthy subjects under MMF. In the healthy subjects, the ratio of forced expiratory volume in one second to forced vital capacity and peak expiratory flow rate were reduced by 22.9% and 52.1%, respectively, after application of MMF, indicating the presence of respiratory obstruction, whereas the ratio of forced vital capacity to predicted forced vital capacity, an indicator of restrictive respiratory defects, was not significantly affected. The obstructive type of respiratory defect was found to be the result of increased airflow resistance with MMF. The decrease of forced expiratory volume was greater in all postoperative patients than in the healthy subjects. The results indicate that careful preoperative and postoperative airway management is essential for the safety of patients undergoing MMF for the treatment of oral and maxillofacial conditions. PMID- 8355107 TI - Masticatory function in patients with mandibular prognathism before and after orthognathic surgery. AB - Masticatory function was analyzed in 54 patients with mandibular prognathism before or after orthognathic treatment and in 40 adults with normal occlusion. Masticatory efficiency was evaluated spectrophotometrically by measuring the amount of adenosine triphosphate eluted from masticated adenosine triphosphate granules. Occlusal contact was evaluated by calculating the number and area of occlusal contacts from the illuminated images of a silicone record of the occlusion that was stored in the image analysis system with the aid of a charge coupled device camera. The mean masticatory efficiency of the preoperative group was approximately half that of the control group. The value for the postoperative group was slightly higher than that for the preoperative group, but there was no statistical difference between the two groups. Likewise, the number and area of occlusal contacts in the preoperative group were also approximately half or less as compared with those of the control group, and they did not show significant changes postoperatively. Statistically, there were correlations between the masticatory efficiency and the number and area of occlusal contacts. The results indicate that although the occlusal relationship of the upper and lower teeth were greatly improved by orthognathic treatment, the postoperative occlusion is not tight enough and may need further adjustment at the end of the treatment. PMID- 8355108 TI - Venous thromboembolic complications in children. PMID- 8355110 TI - Pediatric critical care and hospital costs under reimbursement by diagnosis related group: effect of clinical and demographic characteristics. AB - OBJECTIVE: To determine the relationship of demographic and clinical variables to cost, to revenue based on diagnosis-related groups, and to profit in patients in a pediatric intensive care unit (PICU). DESIGN: Prospective collection of clinical and demographic data of patients sampled. Detailed financial data for all patients discharged from the hospital were compiled by the office of financial planning. A combined data set was used for analysis. SETTING: A multidisciplinary PICU within a general, tertiary-care, teaching hospital in an urban environment. PATIENTS: Consecutive sample of 1174 pediatric patients discharged from the PICU during a 24-month period. MEASUREMENTS AND MAIN RESULTS: Hospital cost (not charges) determined according to industry standards. Revenue was determined by the DRG system. Of the 1174 cases identified, DRG coding and financial data were 97% complete. The mean loss (negative profit) per patient was $9218 +/- $33,676. Profit was significantly and adversely affected by outlier status, death, high risk of death, interhospital transfer, emergency admission, young age, and mechanical ventilation. Multivariate analysis revealed that duration of stay, death, interhospital transfer, and age negatively correlated with profit. CONCLUSION: Under a DRG-based reimbursement system, the operation of an active PICU with a broad referral base may not be desirable from a financial perspective. Similar studies at other institutions could help establish a data base with which the DRG system can be refined. PMID- 8355109 TI - Distinction between transient hyperglycemia and early insulin-dependent diabetes mellitus in childhood: a prospective study of incidence and prognostic factors. AB - We prospectively studied 63 children with transient hyperglycemia to determine their risk of acquiring insulin-dependent diabetes mellitus (IDDM) and to evaluate the predictive value of immunologic markers of prediabetes and of the intravenous glucose tolerance test. Children with transient hyperglycemia were identified by a prospective systematic review of the laboratory reports of a large children's hospital and an office-based pediatric practice and by referral from pediatricians. Transient hyperglycemia occurred in 0.46% of children seen in the children's hospital and in 0.013% of children attending a pediatric office practice. Insulin-dependent diabetes mellitus developed within 18 months of identification in 32% of children in whom transient hyperglycemia was discovered in the absence of a serious illness, compared with 2.3% of children identified during a serious illness (relative risk, 13.9; 95% confidence interval, 1.56 to 123.5). Islet cell antibodies and competitive insulin autoantibodies each had a 100% positive predictive value for IDDM; the negative predictive value of islet cell antibodies and competitive insulin autoantibodies was 96% and 98%, respectively. The stimulated insulin release during an intravenous glucose tolerance test, adjusted for age, had the highest overall accuracy of prediction. All children less than 6 years of age with stimulated insulin release levels < 85 pmol/L (12 microU/ml) subsequently had IDDM, as did an 11-year-old child whose stimulated insulin release level was below the 1st percentile of 170 pmol/L (24 microU/ml). To date, no child whose stimulated insulin release level was above the 5th percentile has had IDDM. We conclude that when transient hyperglycemia occurs during a serious intercurrent illness, the risk of progression to IDDM is low. In contrast, one third of children in whom transient hyperglycemia is identified without a serious illness can be expected to have IDDM within 1 year. A combination of islet cell antibodies, competitive insulin autoantibodies, and stimulated insulin release levels during an intravenous glucose tolerance test can accurately distinguish children with prediabetes from those with presumed benign transient increases in plasma glucose concentrations. PMID- 8355111 TI - Effect of hypogonadism and deficient calcium intake on bone density in patients with galactosemia. AB - Forty children and adults with classic galactosemia had vertebral bone density determined by standard quantitative computed tomography at 3.4 to 44.2 years of age. Compared with age- and sex-matched control subjects, patients with galactosemia had diminished bone density (p = < 0.001). Prepubertal patients of both sexes had bone density determinations below those of the control group (p = 0.008); similar findings were seen in postpubertal patients as well (women, p = 0.001; men, p = 0.008). Women receiving replacement estrogen-progestin therapy for premature ovarian failure had abnormal bone density (136.3 +/- 17.3 mg/cm3 vs 166.0 +/- 17.5 mg/cm3 for control subjects; p = 0.002); patients with evidence of ovarian insufficiency not receiving replacement sex steroids had even lower bone density (92.4 +/- 14.3 mg/cm3 vs 160.2 +/- 20.2 mg/cm3 for control subjects; p < 0.001). Calcium intake for the entire galactosemia group was 540 +/- 344 mg/day. Calcium intake correlated positively with bone density in women given exogenous estrogen (r = 0.87; p = 0.002) and in men (r = 0.74; p = 0.009). Thus the diminished mineralization of bones appears to be another abnormality associated with galactosemia. The results of our study suggest that this is likely secondary to abnormal levels of sex steroids in female patients, low calcium intake, and perhaps an intrinsic defect in the normal galactosylation of the collagen matrix of bone caused by the enzyme defect. Strategies to improve bone formation should be considered to diminish morbidity in patients with this inborn error of metabolism. PMID- 8355112 TI - Percutaneous gastrojejunostomy versus Nissen fundoplication for enteral feeding of the neurologically impaired child with gastroesophageal reflux. AB - To determine the optimal method of providing enteral feeding to neurologically impaired children with gastroesophageal reflux, Nissen fundoplication with simultaneous gastrostomy tube placement (NGT) was compared with anterograde percutaneous gastrojejunostomy (APGJ), a nonsurgical procedure performed under fluoroscopic guidance. The records of 112 neurologically impaired children with gastroesophageal reflux were retrospectively reviewed; 68 had undergone NGT and 44 APGJ. Follow-up data were available for 45 NGT patients (mean age, 6.4 years) and 34 APGJ patients (mean age, 7.9 years). Mean follow-up was 1.8 years in the NGT group and 2.5 years in the APGJ group. Complications resulting from either procedure were classified either as major, which included treatment failures or morbidity resulting in prolonged hospitalization, or as minor, those requiring outpatient treatment only or not directly caused by the procedure. The NGT group had a significantly higher incidence of major complications in comparison with the APGJ group (33.3% vs 11.8%, p < 0.05). Ten patients (22.2%) in the NGT group required reoperation for complications; six required a second NGT for wrap hernia, failure, and continued gastroesophageal reflux. Two patients (5.9%) in the APGJ group required surgery for complications; one of these eventually required an NGT, and the other had an intussusception that necessitated a small bowel resection. Minor complications were more common in the APGJ group than in the NGT group (44.1% vs 6.6%); the majority of complications were related to the jejunostomy tube. Premature replacement or reinsertion of the jejunostomy tube was necessary in 14 APGJ patients (32%). The mortality rate was 8.8% in the NGT group and 5.9% in the APGJ group (p = not significant). No death occurred within 30 days of either procedure. We conclude that APGJ is a safe alternative method for feeding the neurologically impaired child with gastroesophageal reflux. PMID- 8355113 TI - Utility of magnetic resonance imaging for management of hemophilic arthropathy in children. AB - We hypothesized that magnetic resonance imaging (MRI) would improve clinical and plain-radiograph assessments of children with hemophilic arthropathy. Thirteen children, aged 7 to 16 years, with severe factor VIII deficiency and one or more target joints were identified. A target joint was defined as a joint into which hemorrhage had occurred at least twice a month for at least the previous 6 months. After review of history, examination, and plain radiography, a recommendation regarding synovectomy or prophylaxis with factor VIII concentrate was made for each target joint. The MRI of each target joint was then reviewed. Fourteen target joints (three elbows, three knees, eight ankles) were evaluated. On the basis of clinical and plain-radiograph data, synovectomy was recommended for five and prophylaxis for seven joints. Discontinuation of prophylaxis was recommended for two ankles in one child. The MRI examination confirmed that four of five potential synovectomy candidates had markedly hypertrophied synovium and could benefit from surgery; one of five was excluded from synovectomy because synovial hypertrophy was minimal. Two of seven children recommended for prophylaxis were given substantially altered plans after MRI. In all, approximately 40% of joint assessments were modified as a result of the MRI findings. We conclude that MRI should be included in the evaluation of some children with hemophilic arthropathy. PMID- 8355114 TI - Normal values for random urinary calcium to creatinine ratios in infancy. AB - OBJECTIVE: To determine normal values for the urinary calcium/creatinine ratio (UCa/Cr) in infants. To assess the impact of short-term supplementation of infant formula with calcium and phosphorus on UCa/Cr in a group of infants. DESIGN: We determined UCa/Cr in randomly collected urine samples from a group of children and adults. Short-term supplementation of infant formula with calcium glycerophosphate was carried out in 21 infants, and UCa/Cr was monitored in a before-and-after trial. SETTING: A pediatric clinic at an academic center (infants and adults), and a day-care center (older children). PARTICIPANTS: A total of 103 infants between 5 days and 7 months of age, 40 infants between 8 and 17 months of age, 41 children between 18 months and 6 years, and 31 adults. RESULTS: The 95th percentiles for molar UCa/Cr for the different age groups were as follows: less than 7 months, 2.42 (0.86 mg/mg); 7 to 18 months, 1.69 (0.60 mg/mg); 19 months to 6 years, 1.18 (0.42 mg/mg); and adults, 0.61 (0.22 mg/mg). Regression analysis indicated a statistically significant decline in average UCa/Cr with age (R2 = 0.115, p < 0.0001 for log (UCa/Cr) vs log (age)). The geometric means for the two groups of infants were significantly greater than those of the older children and the adults (p < 0.05). Values for UCa/Cr in adults in our sample were comparable to those previously reported. We detected no significant changes in mean UCa/Cr during week-long periods of calcium supplementation of up to 1.8 gm of calcium and 1.39 gm of phosphorus per liter of formula. CONCLUSION: We conclude that normal values for UCa/Cr are much higher in infants than in older children and adults; UCa/Cr is age-related and declines gradually in the first several years of life, and short-term supplementation of infant formula with calcium glycerophosphate has minimal effect on UCa/Cr. PMID- 8355115 TI - Urethral obstruction sequence and lower limb deficiency: evidence for the vascular disruption hypothesis. AB - We reviewed five unreported examples and 23 previously reported cases of urethral obstruction sequence with associated lower limb deficiency. There was no evidence of amniotic bands or exposure to vasoactive drugs during pregnancy in any case. In three infants a gangrenous lesion at the distal part of the affected leg was found; in another three infants, necrotic tissue was noted in the stump of the affected leg. This type of lesion can be explained only on a vascular ischemic basis. In five cases, signs of compression of the external iliac artery by the grossly distended bladder, by grossly distended ureters, or both were found. A vascular disruption in the territory of the external iliac artery caused by compression by the distended urinary tract is the proposed mechanism for the associated limb deficiency. PMID- 8355117 TI - Prospective payment and pediatric intensive care. PMID- 8355116 TI - Variable phenotypes in velocardiofacial syndrome with chromosomal deletion. AB - Velocardiofacial syndrome (VCF) has overlapping features with DiGeorge sequence; both result from a developmental field defect and probably represent contiguous gene deletion syndromes. The association of chromosome 22q11 deletion with DiGeorge sequence led us to do molecular analysis of chromosome 22 in 18 patients with VCF, who ranged in age from 6 to 42 years. All 18 patients had monosomy for the chromosome region 22q11. Retrospectively, we correlated the presence of the deletion with various clinical findings: 100% had cleft palate, 67% the facial phenotype, 83% cardiac disease, 94% learning disabilities, 70% ophthalmologic findings, 50% short stature, 22% psychiatric disorders, and 17% hypocalcemia. Both severely phenotypically affected and mildly affected patients had the deletion. These findings stress the importance of continued surveillance of all patients with VCF for the many medical problems that may not be present at initial diagnosis. We conclude that the presence of the gene deletion does not predict the phenotypic expression in VCF. Further studies to characterize the size of the gene deletion may facilitate better prediction of the phenotype. PMID- 8355118 TI - Recurrent apparent life-threatening events during infancy: a manifestation of inborn errors of metabolism. AB - To determine how often inborn errors of metabolism may cause unexplained apnea or recurrent apparent life-threatening events in infants, we retrospectively reviewed the records of 166 infants who were referred for apnea evaluation. A metabolic disorder was identified in 7 infants (4.2%), all of whom had recurrent apparent life-threatening events. PMID- 8355119 TI - Microbiology of kerions. AB - Qualitative and semiquantitative bacterial culture specimens were obtained from 44 patients with kerions. Staphylococcus aureus was isolated from the scalp surface overlying the kerion in 29% of patients and from the pus within the kerion in 48% of patients. Gram-negative bacteria were found in the same locations in 11.3% and 18% of patients, respectively. The data indicate that bacteria are frequently cultured from kerions. PMID- 8355120 TI - A new, rapid, noninvasive screening test for celiac disease. AB - Serum levels of IgA and IgG antigliadin antibodies were evaluated in 267 subjects by using both the classic enzyme-linked immunosorbent assay and a rapid test (strip-AGA test) performed on a drop of whole blood. This new test was easy to perform and gave results comparable to those of the enzyme-linked immunosorbent assay; it could be useful in screening for celiac disease in both at-risk and normal populations. PMID- 8355121 TI - Transient improvement of congenital lactic acidosis in a male infant with pyruvate decarboxylase deficiency treated with dichloroacetate. AB - A comatose male newborn infant with congenital lactic acidosis caused by pyruvate decarboxylase deficiency was treated with dichloroacetate (DCA), which stimulated an 88% drop in serum lactate concentration and reversed his coma. The response to DCA was temporary and the lactic acidosis worsened until his death, but DCA may confer more lasting benefit in less severely affected infants. PMID- 8355122 TI - Hereditary motor-sensory neuropathy (Charcot-Marie-Tooth disease) with nerve deafness: a new variant. AB - Hereditary motor-sensory neuropathy with sensorineural deafness is described in a family; the neurologic features and deafness were apparent in early childhood and infancy. The clinical syndrome in the family was not closely linked to the Duffy blood group, nor was duplication demonstrated at the disease-associated locus 17 p11.2. This family may represent a different form of this heterogeneous disease. PMID- 8355123 TI - Plasma nitric oxide levels in newborn infants with sepsis. AB - Nitric oxide is thought to play an important role in the mediation of the cardiovascular features of septic shock. We determined plasma levels of nitrite and nitrate (not differentiated in measurement) in neonates with sepsis and found these levels to be elevated at the time of entry compared with those of control subjects (p < 0.05); the levels were significantly higher in the patients with sepsis and shock than in those without shock (p < 0.05). Elevations of nitrite plus nitrate were correlated with tumor necrosis factor and severity of illness judged by pediatric risk of mortality (PRISM) scores at onset (p < 0.05). Of 8 newborn infants with a nitrite-plus-nitrate value > 200 mumol/L, 6 had septic shock; none of 12 not reaching that cutoff value had septic shock (p < 0.05). Levels of nitrite plus nitrate were elevated as much in gram-positive as in gram negative sepsis. We conclude that the determination of circulating plasma levels of nitrite plus nitrate may be useful in forecasting the severity of illness and the occurrence of septic shock; therapeutic approaches associated with inhibition of nitric oxide synthesis may be worth trying in infants with septic shock. PMID- 8355124 TI - Growth and bone mineral status of discharged very low birth weight infants fed different formulas or human milk. AB - The objective of this study was to determine whether the growth and bone mineral status of discharged preterm infants fed human milk differed from those of infants fed one of three different formulas varying in calcium content (545 mg/L, 660 mg/L, or 1290 mg/L). A randomized, blinded study was conducted for 16 weeks after discharge in 16 human milk-fed and 43 formula-fed infants. All formula-fed infants received one of the three study formulas from discharge to 8 weeks afterward, and the standard formula, which contained 545 mg/L calcium, from 8 to 16 weeks. The human milk-fed infants gained weight more slowly than the formula fed infants. The human milk-fed infants also had lower gains in length and higher serum alkaline phosphatase values than the formula-fed infants. The infants who received the formula containing the highest calcium concentration (1290 mg/L) had greater bone mineral density during the first 8 weeks of the study. We conclude that preterm infants recently discharged from the hospital may benefit from higher calcium intake than is provided by either human milk or standard term formula. PMID- 8355125 TI - Measurement of true absorption, endogenous fecal excretion, urinary excretion, and retention of calcium in term infants by using a dual-tracer, stable-isotope method. AB - A dual-tracer, stable-isotope method was used to measure the percentage of true calcium absorption (alpha), true calcium absorption rate (Va), endogenous fecal calcium excretion rate (Vf), urinary calcium excretion rate (Vu), and calcium retention rate (Vr). Twenty-seven infants with a mean gestation of 30.6 +/- 1.7 weeks and a mean birth weight of 1.4 +/- 0.21 kg were studied at 2 or 3 weeks of age, or both, during feedings of human milk (HM), fortified human milk (HMF), and commercially available formula (20 or 24 calories per ounce) for premature infants (EPF-20/780 and EPF-24/940) (part 1 of our study). Of 13 additional infants with a mean (+/- SD) birth weight of 1.26 +/- 0.25 kg and gestation of 29.6 +/- 2.5 weeks, 11 completed a crossover-design study at 2 and 3 weeks of age, receiving two identical formulas containing calcium, 940 mg/L, and phosphorus, 470 mg/L (EPF-24/940 formula) or calcium 1340 mg/L, and phosphorus, 680 mg/L (EPF-24/1340 formula) (part 2 of our study). The alpha value was higher in infants receiving HM (76.4 +/- 15.1%) or HMF (68.0 +/- 7.8%) than in those receiving EPF-20/750 formula (54.1% +/- 5.6%) or in previously reported infants fed standard formula (47.1% +/- 11.5%); those given EPF-24/940 formula had intermediate values (63.9% +/- 13.9%, part 1; 56.1% +/- 16.5%, part 2). No significant differences existed among groups for either Vu or Vf per kilogram. In the crossover study (part 2), no significant differences were seen between formulas for alpha and for Va, Vf, or Vr per kilogram. However, Vu per kilogram was significantly decreased in infants receiving the higher mineral formula (EPF 24/940: 3.6 +/- 2.3; EPF-24/1340: 2.9 +/- 2.3 mg/kg per day; p = < 0.005). With all feedings, alpha, Vu per kilogram, and Vf per kilogram were not related to gestational age, age at study, calcium intake, or each other. However, Vf per kilogram was inversely related to birth weight. Thus, alpha, Vu, and Vf appear to be independent and may be differentially affected by factors altering calcium dynamics. We conclude that increasing formula mineral content does not ensure increased retention; careful monitoring of individual infants remains indicated. PMID- 8355126 TI - Measurement of nutrient intake by deuterium dilution in premature infants. AB - To assess whether a simple nonrestrictive method of determining nutrient intake could be applied to premature infants, we compared actual measured formula intake during a 7-day period with intake calculated from deuterium dilution in 13 hospitalized, growing, premature newborn infants. An oral dose of deuterium oxide (D2O) was administered, and urine samples were analyzed by deuterium nuclear magnetic resonance spectrometry for D2O concentration. Using an exponential model, we calculated formula intake from the decline in D2O concentration during the 7-day study period. Intake as assessed by the deuterium model correlated well with actual intake (r = 0.93; p < 0.001). However, because the deuterium dilution model measures both dietary and nondietary water intake (metabolic and cutaneous water influx), deuterium dilution-derived intake exceeded actual intake by 25 +/- 18 ml/kg per day (16% +/- 11%). When corrections were applied to account for nondietary water intake, deuterium dilution-derived nutrient intake (160 +/- 30 ml/kg per day) closely approximated actual intake (155 +/- 17 ml/kg per day). If corrections are made for nondietary water intake, the deuterium dilution method may be a useful nonrestrictive method of measuring nutrient intake in a variety of neonatal populations. PMID- 8355127 TI - Subcutaneous fat necrosis in a neonate, in association with aberrant plasma lipid and lipoprotein values. AB - A newborn infant with subcutaneous fat necrosis after perinatal hypoxia was found to have several abnormalities of plasma lipids. Further studies are needed to determine whether such abnormalities contribute to the pathophysiology of the skin lesions. PMID- 8355128 TI - Lymphocyte subpopulations in healthy newborn infants: comparison of cord blood values with values five days after birth. AB - Significant differences (p < 0.0001) were demonstrated in lymphocyte subpopulations both in cord blood and in venous blood samples obtained at day 5 from the same healthy infants. Numbers of T lymphocytes increased, especially CD4+/CD45RA+ cells, whereas numbers of B lymphocytes and natural killer cells decreased without changes in CD8+ and other cytotoxic cells. PMID- 8355129 TI - Rapid cocaine screening of urine in a newborn nursery. AB - A rapid cocaine screening test, the Abuscreen OnTrak assay, was compared with the EMIT (enzyme-multiplied immunoassay technique) screening test to determine relative accuracy in 450 newborn infants sequentially tested for urinary cocaine during a 6-week period at a large urban hospital. The Abuscreen Ontrak screen had a sensitivity of 96% and a specificity of 100%. PMID- 8355130 TI - Clement Andrew Smith. PMID- 8355131 TI - Identifying febrile infants at risk for a serious bacterial infection. PMID- 8355132 TI - Beclomethasone for treating premature infants with bronchopulmonary dysplasia. PMID- 8355133 TI - Nebulized salbutamol versus racemic epinephrine in the treatment of infants with bronchiolitis. PMID- 8355134 TI - Blood lactate concentrations and neonatal sepsis. PMID- 8355135 TI - Group B streptococcus serotype V. PMID- 8355136 TI - Treatment of congenital alveolar proteinosis. PMID- 8355137 TI - Hypercalcemic phase of Williams syndrome. PMID- 8355139 TI - Does childhood personality predict longevity? AB - Key models relating personality and health predict that personality in childhood is indicative of later health and longevity. Longevity predictions are tested using data derived from the 7-decade longitudinal study initiated by L. M. Terman 1921 (L. M. Terman & M. H. Oden, 1947). Variables representing major dimensions of personality are used in statistical survival analyses of longevity in 1,178 males and females. Conscientiousness in childhood was clearly related to survival in middle to old age. This finding (a) establishes that childhood personality is related to survival decades into the future, (b) confirms the validity of the conscientiousness dimension in conceptualizing personality, and (c) points to likely and unlikely pathways linking personality to health. Contrary to expectation, cheerfulness (optimism and sense of humor) was inversely related to longevity, suggesting a possible need for reconceptualization of its health relevance. PMID- 8355138 TI - Effects of motivationally significant stimuli on the regulation of dominant responses. AB - In 4 experiments, Ss responded as quickly as possible to indicate whether character strings consisted of letters or numbers. Following a warning stimulus that was or was not designed to trigger a motivational-emotional response in particular subgroups (viz., those with high anxiety, discrepant self-concepts, and eating disorders), strings were presented in a central (dominant) location on 75% of the trials or in 1 of 4 peripheral (nondominant) locations. Consistent with hypotheses, response times to peripherally located strings were significantly slower following motivationally significant than following neutral warning stimuli. Contrary to hypotheses, such stimuli did not facilitate responding to centrally located strings. It is proposed that motivationally significant stimuli engender a temporary reduction in control processing that hinders regulation of dominant responses. PMID- 8355140 TI - Self-esteem and counterfactual thinking. AB - Two studies examined the relation between self-esteem and counterfactual thinking (consideration of "might-have-been" alternatives to reality). Ss imagined themselves in scenarios with another actor that resulted in either success or failure. Ss then "undid" the outcome by altering events that preceded the outcome. Following success, high self-esteem (HSE) Ss were more likely than low self-esteem (LSE) Ss to mutate their own actions. Following failure, LSE Ss were more likely than HSE Ss to mutate their own actions. Also, the structure of counterfactuals was influenced by outcome valence but not by self-esteem: Subtractive structures (in which antecedents are removed) were elicited by success, whereas additive structures (in which antecedents are added) were elicited by failure. The importance of the self and individual differences in self-esteem to counterfactual thinking is discussed. PMID- 8355141 TI - Duration neglect in retrospective evaluations of affective episodes. AB - Two experiments documented a phenomenon of duration neglect in people's global evaluations of past affective experiences. In Study 1, 32 Ss viewed aversive film clips and pleasant film clips that varied in duration and intensity. Ss provided real-time ratings of affect during each clip and global evaluations of each clip when it was over. In Study 2, 96 Ss viewed these same clips and later ranked them by their contribution to an overall experience of pleasantness (or unpleasantness). Experimental Ss ranked the films from memory; control Ss were informed of the ranking task in advance and encouraged to make evaluations on line. Effects of film duration on retrospective evaluations were small, entirely explained by changes in real-time affect and further reduced when made from memory. Retrospective evaluations appear to be determined by a weighted average of "snapshots" of the actual affective experience, as if duration did not matter. PMID- 8355142 TI - Rudimentary determinants of attitudes. II: Arm flexion and extension have differential effects on attitudes. AB - In the pain-flexor reflex, arm extension is temporally coupled with the onset of the unconditioned aversive stimulus, whereas flexion is associated with its offset; when retrieving desirable stimuli, arm flexion is more closely coupled temporally to the acquisition or consumption of the desired stimuli than arm extension. It was posited that these contingencies foster an association between arm flexion, in contrast to extension, and approach motivational orientations. Six experiments were conducted to examine this hypothesis. Ideographs presented during arm flexion were subsequently ranked more positively than ideographs presented during arm extension, but only when the Ss' task was to evaluate the ideographs when they were presented initially. Arm flexion and extension were also each found to have discernible attitudinal effects. These results suggest a possible role for nondeclarative memory in attitude formation. PMID- 8355143 TI - Is human mating adventitious or the result of lawful choice? A twin study of mate selection. AB - Pairs of middle-aged twins and their spouses provided data on 74 mainly psychological variables. Neither spousal similarity nor idiosyncratic criteria could account for specific mate selection in these 738 couples. Of the twins (and their spouses), 547 independently rated their initial attraction to their twin's mate (or to their spouse's twin): Findings suggest that characteristics both of the chooser and the chosen constrain mate selection only weakly. This article proposes that it is romantic infatuation that commonly determines the final choice from a broad field of potential eligibles and that this phenomenon is inherently random, in the same sense as is imprinting in precocial birds. PMID- 8355144 TI - They don't all look alike: individuated impressions of other racial groups. AB - Reliability, content, and homogeneity of own- and other-race impressions were assessed: U.S. White, U.S. Black, and Korean students rated faces of White, Black, or Korean men. High intraracial reliabilities revealed that people of 1 race showed equally high agreement regarding the traits of own- and other-race faces. Racially universal appearance stereotypes--the attractiveness halo effect and the babyface overgeneralization effect--contributed substantially to interracial agreement, which was only marginally lower than intraracial agreement. Moreover, similar attention to variations in appearance yielded similar degrees of own- and other-race trait differentiation. When own- and other race differences in the differentiation of faces on babyfaceness were statistically controlled, differences in trait differentiation were eliminated. Despite the individuated impressions of other-race faces, certain racial stereotypes persisted. PMID- 8355145 TI - [Development and pharmaceutical evaluation of hydrophobic cyclodextrin derivatives as modified-release drug carriers]. AB - Hydrophobic cyclodextrin (CyD) derivatives, such as 2,6-di-O-ethyl-beta-CyD (DE beta-CyD), 2,3,6-tri-O-ethyl-beta-CyD (TE-beta-CyD), carboxymethylethyl-beta-CyDs (CME-beta-CyDs) with different degrees of substitution, 2,3,6-tri-O-acyl-beta CyDs with different alkyl chains (C1-C12) were prepared and their chemical structures and physicochemical properties were elucidated. Furthermore, possible utilities of hydrophilic and hydrophobic CyD derivatives as modified-release drug carriers were evaluated on the basis of in vitro/in vivo correlations. The results obtained in this study are as follows: (1) Hydrophilic CyDs such as 2 hydroxypropyl-beta-CyD are useful as immediate-release type carriers for poorly water-soluble drugs such as nifedipine. (2) Hydrophobic CyDs such as ethylated and acylated beta-CyDs can be used as prolonged-release type carriers for water soluble drugs such as diltiazem hydrochloride, buserelin acetate and molsidomine. (3) Enteric CME-beta-CyD derivatives are useful as delayed-release type carriers, and also as stabilizers for prostaglandin E and carmofur which are labile under alkaline conditions. (4) Various release rates can be obtained by combining hydrophilic and hydrophobic CyD derivatives in appropriate mixing ratios, e.g., double-layer tablets consisting of beta-CyD complex and DE-beta-CyD/CME-beta-CyD complexes released drugs rapidly at an initial stage, followed by slow release. The combination of CyD derivatives and pharmaceutical additives was also useful to modify the release rate of various drug molecules. PMID- 8355146 TI - [Synthesis of acyclic 1,3-polyols and its application to structural study of natural products]. AB - A 1,3-polyhydroxylated chain is often found on the backbone of biologically important natural products. The acyclic nature and the regular array of many hydroxyl groups are main obstacles to structural and synthetic studies, and many efforts have been made to this end. We have developed a new general synthetic method of 1,3-polyols based on the coupling of a chiral dithiane, a four-carbon unit, and an epoxide, followed by 1,3-diastereoselective reduction. We applied the method to the synthesis of polymethoxy-1-alkenes isolated from blue-green algae to establish their absolute stereochemistry. Moreover, a general procedure for assigning the absolute stereochemistry of acyclic 1,3-polyols by the difference circular dichroism (CD) method have been established. Combination of the method and a reiterative degradation enables one to determine the absolute configuration of 1,3-polyols, even if the relative stereochemistry is unknown. PMID- 8355147 TI - [Quenching of ethidium-DNA fluorescence by novel acridines with antitumor activities. II. The structure-activity relationship in acridines with fluorescence quenching of ethidium-DNA]. AB - In order to elucidate the structure-activity relationship between the antitumor activity and the molecular structure of novel DNA-intercalator acridine derivatives (1a-g and 2a-i in Chart 1), DNA-binding properties (intercalation) of these acridines were examined by quenching in the fluorescence of the ethidium DNA complex. The mechanism of quenching is caused by the displacement of DNA bound ethidium by a second DNA binding ligand, acridines. The concentration (C50 value) of acridine necessary to reduce the initial fluorescence of DNA-bound ethidium by 50% showed a good correlation with their antitumor activities. The quenching of fluorescence for acridines was examined using amsacrine (AMSA) as a typical standard of the second DNA-bound ligand, and calf thymus DNA with an apparent site size of two base pair. Some of the acridine derivatives showed more potent quenching of fluorescence than amsacrine (AMSA). PMID- 8355148 TI - [Chemical fluctuation of the constituents during the drying of Ginseng radix and Ginseng radix Rubra. Crude drug processing by far-infrared treatment]. AB - In order to evaluate the utility of far-infrared drying method for crude drugs, the efficiency in the drying process of Ginseng Radix and Ginseng Radix Rubra was examined. Furthermore, chemical fluctuation of the constituents of Ginseng Radix and Ginseng Radix Rubra, which may occur during their drying process, has been investigated by means of HPLC quantitative analysis for ginsenosides and malonyl ginsenosides, and TLC qualitative analysis for lipophylic constituents. It has been found that the far-infrared drying method (oven temperature 45 degrees C) dried Ginseng Radix faster without reducing both ginsenosides and malonyl ginsenosides in comparison with the conventional drying methods such as an air drying and a hot-air drying. PMID- 8355149 TI - Learning from the mistakes of the past. PMID- 8355150 TI - One year postoperative astigmatic comparison of sutured and unsutured 4.0 mm scleral pocket incisions. AB - The postoperative astigmatic course of unsutured and sutured 4.0 mm scleral pocket incisions was followed for one year in a small pilot study. Initially, with-the-rule changes were noted only in the sutured group; eventually both groups demonstrated a small against-the-rule change that did not differ clinically or statistically. At one year after surgery the group without suture closure developed a -0.45 diopter (D) shift while a -0.34 D change was noted in the group closed with the anchor suture method. The unsutured group of eyes demonstrated physical stability as did those eyes with suture closure; no cases developed wound leaks, hypotony, or filtration blebs. Mean intraocular pressure was statistically unchanged from preoperative levels at one day after surgery for both groups. No case demonstrated postoperative endophthalmitis. Properly performed no-stitch corneal valve incisions provide physical and astigmatic stability that is indistinguishable from sutured incisions. PMID- 8355151 TI - Relative strength of scleral tunnel incisions with internal corneal lips constructed in cadaver eyes. AB - We constructed scleral tunnel wounds with internal corneal lips and sutureless closures in ten cadaver eyes without previous intraocular surgery. Each wound differed in width, total incision length, and internal corneal lip size. At a low and high range of initial intraocular pressure (IOP, 10 to 15 mm Hg or 20 to 25 mm Hg), we compared the wounds' resistance to leakage during application of external pressure. A square wound with a 4.0 mm width and 4.0 mm overall length, including a 1.5 mm corneal lip, had the optimum wound dimensions. These produced a stable incision that resisted leakage at external pressures up to 525 pounds per square inch equally well at both IOP ranges. Leakage occurred at lower external pressures for wounds with greater width, smaller corneal lips, or wound widths that were greater than wound lengths; such wounds were also more prone to leakage at the low IOP range. When constructed properly and adequately, the 4.0 mm wide scleral tunnel incision with 1.5 mm internal corneal lip is a strong and safe wound for sutureless cataract surgery. PMID- 8355152 TI - Inhibition of posterior capsule opacification: the effect of colchicine in a sustained drug delivery system. AB - We investigated the effect of colchicine in a sustained drug delivery system on posterior capsule opacification (PCO) in rabbit eyes. A polymer matrix wafer, which diffused colchicine at a steady rate, was implanted in the capsular bag of 34 eyes after the lens material was removed by endocapsular phacoemulsification. Three different drug concentrations were used in the rabbit eyes, which were compared with control eyes containing the polymer matrix wafer without colchicine. The mean PCO score was highest in the control group without colchicine and increased steadily over 12 weeks. The rate of PCO formation in all eyes treated with colchicine was significantly lower than in the control group. There was no statistically significant improvement in PCO inhibition with the higher colchicine dosages. Side effects included inflammatory anterior chamber reaction and corneal and retinal complications and were most notable with the highest drug concentration. Slow release of colchicine reduces PCO formation in the rabbit. The optimal biocompatible dosage must be carefully determined and warrants further investigation. PMID- 8355153 TI - Early central posterior capsular fibrosis in sulcus-fixated biconvex intraocular lenses. AB - A series of 228 eyes implanted with one-piece all poly(methyl methacrylate) (PMMA) biconvex posterior chamber intraocular lenses was examined for posterior capsule opacification. One hundred forty-one eyes (61.8%) had opacification at an average postoperative period of 19.7 months. Seventy eyes (30.7%) developed an unusual form of early central posterior capsular fibrosis (ECPCF), which was confined to the capsulorhexis opening, sparing the peripheral aspect of the anterior and posterior capsules. Risk factors for developing this form of opacification were close apposition of peripheral anterior and posterior capsules caused by placing a posteriorly vaulted biconvex optic anterior to a capsulorhexis opening smaller than the optic diameter. This opacification occurred most often in cases of haptic fixation in the ciliary sulcus. The cumulative capsulotomy rate in this series was 5.26% at three months, 9.1% at 12 months, and 13.2% at 20 months. Of the ECPCF cases, 34.3% eventually required neodymium: YAG (Nd:YAG) laser capsulotomy; the capsulotomy rate for ECPCF was 4.8 times higher than that for Elschnig pearls. Early onset of ECPCF (average onset = 19.4 weeks) resulted in early Nd:YAG capsulotomy (average = 8.0 months after surgery). One-piece all-PMMA biconvex intraocular lenses may promote early central fibrosis of the posterior capsule if the lens optic is anterior to a capsulorhexis opening smaller than the optic diameter. The early onset of this form of opacification predisposes to earlier Nd:YAG capsulotomy with a higher risk of complications. PMID- 8355154 TI - Flurbiprofen 0.03% for the control of inflammation following cataract extraction by phacoemulsification. AB - We conducted a double-masked, vehicle-controlled study to evaluate the anti inflammatory effect of topical flurbiprofen in cataract surgery by phacoemulsification and implantation of a posterior chamber intraocular lens. The 233 patients were randomized to receive either flurbiprofen or vehicle immediately prior to and for two weeks following surgery. No concomitant corticosteroid use was allowed. The flurbiprofen group had significantly less anterior chamber cells and flare at day 7 and significantly less conjunctival erythema, corneal edema, and lid edema at day 14. The investigator's global effectiveness rating was higher in the flurbiprofen group at day 14. Blood aqueous barrier disruption, as measured by aqueous fluorophotometry, was statistically significantly diminished in the flurbiprofen group. Burning and stinging were rated significantly greater in the flurbiprofen group than in the vehicle group. Foreign-body sensation and photophobia were significantly more severe in the vehicle group than in the flurbiprofen group. Flurbiprofen provided postsurgical anti-inflammatory efficacy in clinical signs of inflammation and in blood-aqueous barrier disruption, and also showed improved subjective signs. PMID- 8355155 TI - Incidence and management of complications of transsclerally sutured posterior chamber lenses. AB - Thirty eyes with an average follow-up of 23 months following transscleral fixation of a posterior chamber intraocular lens (IOL) were retrospectively reviewed for complications. The most common complication was erosion of the polypropylene suture knots through half thickness scleral flaps (22 eyes, 73%). The average time for suture erosion through the sclera was 9.4 months (range one to 12). The polypropylene suture knots eroded through the conjunctiva in five eyes (17% incidence) at an average of 12 months postoperatively (range six to 18 months). All conjunctival erosions were surgically repaired. Other complications included clinically significant lens tilt/decentration (3/30, 10%), open angle glaucoma (5/30, 17%), and suprachoroidal hemorrhage (1/30, 3%). The complications associated with transscleral fixation of posterior chamber IOLs are distinctly different from those associated with anterior chamber IOLs. Prospective clinical trials may provide further information about pseudophakic rehabilitation in the absence of capsular support. PMID- 8355156 TI - Effect of incision size on early postoperative visual rehabilitation after cataract surgery and intraocular lens implantation. AB - One hundred fifty-one unilateral cataract patients were randomly assigned to receive either a one-piece Staar AA-4203 silicone intraocular lens inserted through a 3.5 mm incision, an loptex 5 mm x 6 mm oval optic lens inserted through a 5.5 mm incision, or an AMO three-piece modified C-loop 6.0 round optic poly(methyl methacrylate) lens inserted through a 6.5 mm incision. Follow-up was 97% at two days postoperatively and 84% at one week and two months postoperatively. At one week postoperatively, 62% of 3.5 mm incision cases had uncorrected visual acuity of 20/40 or better compared with 33% of 5.5 mm (P < .01) and 43% of 6.5 mm incision cases. At two months postoperatively, 85% of 3.5 mm incision cases had uncorrected visual acuity of 20/40 or better compared with 64% of 6.5 mm (P < .05) and 71% of 5.5 mm incision cases. The 3.5 mm incision cases had significantly less total keratometric cylinder than other cases at all postoperative examinations (P < or = .001) and less surgically induced cylinder at two days and one week post-operatively (P < or = .02). The 5.5 mm and 6.5 mm incision cases did not differ significantly in visual acuity or astigmatism at any examination. PMID- 8355157 TI - Intraocular lens performance in air, in water, and in situ: a computer study. AB - Computer analysis is used to predict performance of four intraocular lenses with assigned values of aberration. Cylinder error and asphericity error are used as examples of possible manufacturing errors. Three measures of performance are calculated: maximum optical path difference, root mean square optical path difference, and modulation transfer function. For evaluation in air these standard test conditions are assumed: collimated green light incident on the convex surface of a plano-convex lens, with a 3 mm aperture. All four lenses show substantially improved performance in water compared to air, and a further improvement in the simulated eye (i.e., in situ). However, an aberrated 30 diopter (D) lens with performance in air comparable to an aberrated 20 D lens, performs worse in situ than does the 20 D lens. This suggests that a performance test in air that is suitable for a 20 D lens (e.g., 100 line pairs per millimeter resolution) may not be adequate for a 30 D lens. A test in air at 30% resolution efficiency may be more suitable. PMID- 8355158 TI - Interpreting multifocal intraocular lens modulation transfer functions. AB - The optical performance of new multifocal intraocular lens designs is frequently assessed using the modulation transfer function (MTF). We discuss the relationship between the MTF and clinical measures of human visual function, such as threshold visual acuity and contrast sensitivity. Using in vitro MTF measurements of a human eye model containing a multifocal or monofocal intraocular lens, we predict relative changes in acuity and contrast sensitivity and outline the techniques using a simple model of human retinal threshold detection. Specific concepts introduced include the visual acuity graph, predicted visual acuity graph, and predicted contrast sensitivity function. PMID- 8355159 TI - Evaluation of contrast acuity and defocus curve in bifocal and monofocal intraocular lenses. AB - We compared visual quality of the following intraocular lenses in a prospective study: monofocal, True Vista bifocal, 3M diffractive bifocal, and Nordan aspheric VariFocal silicone. Four to six months postoperatively we measured distance acuity, Snellen near acuity (Lighthouse chart), reading acuity (Nieden chart), and contrast acuity at far and near focus (Regan charts: 96%, 50%, 25%, 11% contrast) with different pupil sizes. A defocus curve was obtained by spectacle defocus (+1 diopter [D] to -5 D). Eleven patients had True Vista in one eye and monofocal in the fellow. Contrast acuity at far focus decreased with decreasing contrast and increasing pupil size. This decrease was more pronounced with the True Vista than with the monofocal lenses. These differences were significant, with a 4.5 mm pupil at lower contrast (25%, P = .02; 11%, P = .01). Depth of focus was 4.5 D (+1.0 D to -2.0 D) with True Vista lenses and 2.5 D (+1.0 D to 1.5 D) with monofocal lenses. Corrected distance acuity was 20/22 with True Vista, 20/25 with 3M, and 20/20 with VariFocal. Distance corrected Snellen near acuity was 20/39 with True Vista, 20/34 with 3M, and 20/57 with VariFocal. Distance corrected reading acuity was 20/29 with True Vista, 20/23 with 3M, and 20/44 with VariFocal (P = .005). Contrast acuity at far focus was best with the VariFocal IOL, followed by True Vista and 3M. At near focus it was best with 3M, followed by True Vista and VariFocal. Contrast acuity at near focus was lower than at far focus. Average acuity differences were as follows: VariFocal 0.43, P = .01; True Vista 0.19, P = .05; 3M 0.04, P = .3. Depth of focus was 4.5 D (+1.0 D to -3.5 D) with True Vista and 3M and was 3 D (+1.0 D to -2.0 D) with VariFocal. Each design offers unique features. VariFocal is best at distance, but near vision is not sufficient. The 3M lens is best at near vision but distance contrast acuity is somewhat reduced. The True Vista lens provides a good compromise as distance contrast acuity is good and near vision is sufficient. PMID- 8355160 TI - A new method of analyzing vectors for changes in astigmatism. AB - This method of astigmatism analysis recognizes the need to define an astigmatism goal, thus allowing the surgeon to obtain precise, separate measures of the magnitude and the angle of surgical error. From this, the surgeon can evaluate what surgery may be required to achieve the initial preoperative goal. An index that measures surgical success is adjusted for the level of preoperative astigmatism. The resulting data allow statistical comparison of multiple surgeries and techniques. This method also assists in resolving the case when spectacle and corneal astigmatism do not coincide. PMID- 8355161 TI - Acute intraoperative suprachoroidal hemorrhage in capsular bag phacoemulsification. AB - Two cases of limited (nonexpulsive) acute intraoperative suprachoroidal hemorrhage (AISH) were identified in a consecutive series of 3,096 cataract surgeries accomplished by capsular bag phacoemulsification--an incidence of 0.06%. This is lower than that reported by me in 1986 when I was using iris plane phacoemulsification (0.81%). I believe the reduction is the result of decreased anatomical distortion from reducing the number and amplitude of intraocular pressure swings experienced by the globe during surgery. The pressure swings result from technique-mandated oscillations in infusion and aspiration dynamics, which are greater in number and amplitude in the iris plane technique. PMID- 8355162 TI - Cataract and intraocular lens implantation after remote trabeculectomy for Sturge Weber syndrome. AB - A 6-year-old patient with Sturge-Weber syndrome and secondary glaucoma had trabeculectomy and subsequent reconstruction of a shallow anterior chamber. Six months later, a dense fibrin clot and anterior capsule cataract developed, requiring surgery. Using the anterior chamber maintainer technique, extracapsular cataract extraction with posterior chamber intraocular lens implantation was performed. Twelve months later visual acuity was 20/30, intraocular pressure was 14 mg Hg, and the anterior chamber was deep and quiet. PMID- 8355163 TI - Corneal incision dehiscence during penetrating keratoplasty nine years after radial keratotomy. AB - As the use of radial keratotomy (RK) to correct myopia increases, more patients are having penetrating keratoplasty (PK). Radial keratotomy incisions are known to show incomplete wound healing. When the radial corneal RK incisions are cut by the corneal trephine, the peripheral part of each incision may open, even years after surgery. In this case, a 56-year-old man had visual distortion and diplopia in one eye nine years after RK. Contact lenses did not correct the problem, and the patient could not tolerate the contact lenses. Penetrating keratoplasty was performed. During surgery about one-third of the peripheral RK incisions spontaneously opened, making suturing difficult. Although the final visual result was 20/20 corrected acuity, this case shows that RK incisions may remain incompletely healed and easily open during PK surgery as long as nine years after the RK surgery. PMID- 8355165 TI - Intraocular lens dislocation in the bag. AB - We report a case in which an intraocular lens dislocated entirely within the capsular bag. The patient was myopic with a large anterior segment. A standard 5 mm x 6 mm phaco profile intraocular lens was found to be completely dislocated on the fifth postoperative day. The dislocated lens was replaced with another posterior chamber intraocular lens sutured at the ciliary sulcus. PMID- 8355164 TI - Intraocular lens encapsulation by shrinkage of the capsulorhexis opening. AB - A 57-year-old man with retinitis pigmentosa and subcapsular cataract had phacoemulsification with a continuous curvilinear capsulorhexis and implantation of a poly(methyl methacrylate) intraocular lens. Six months later, the patient presented with blurred vision and severe anterior capsule fibrosis which led to complete posterior chamber lens encapsulation. PMID- 8355166 TI - V-style phacoemulsification. AB - A technique designed to reduce zonular stress and ensure safe intercapsular phacoemulsification is described. This one-handed method is especially effective in eyes with strong adhesions between nucleus and cortical layers where hydrodissection is not possible. Early experiences in 150 eyes yielded a reduction in emulsification time and such intraoperative complications as posterior capsule rupture and zonulysis. PMID- 8355167 TI - Phacoemulsification with poorly dilated pupils. AB - Tilting the viewing angle of the operating microscope during phacoemulsification provides the surgeon a better view of the cataractous lens. This technique, combined with continuous curvilinear capsulorhexis, divide and conquer nucleofractis, and lens rotation in the capsular bag, allows the surgeon to perform most of the phacoemulsification procedure near a well-visualized 6 o'clock meridian. This procedure can eliminate the need for iris surgery in cases with small pupils. Also discussed is the removal of the upper half of the cortical substance in patients with small pupils. PMID- 8355168 TI - Knife for performing the initial groove for sutureless cataract surgery. PMID- 8355169 TI - Keratome for sutureless cataract surgery. PMID- 8355170 TI - Consultation section. Request for vision improvement six years after bilateral radial keratometry. PMID- 8355171 TI - Peribulbar block injection volume. PMID- 8355172 TI - Potential difference in astigmatism obtained by manual and automated keratometers. PMID- 8355173 TI - Night glare and excimer laser ablation diameter. PMID- 8355174 TI - Transscleral suturing of posterior chamber lenses. PMID- 8355175 TI - Caines produce pain. PMID- 8355176 TI - Blood in the capsular bag--endocapsular hematoma not a hyphema. PMID- 8355177 TI - Phaco interruptus. PMID- 8355178 TI - Myocardial uptake and pharmacodynamics of procainamide in patients with coronary heart disease and sustained ventricular tachyarrhythmias. AB - Little information is available currently regarding the time course of myocardial accumulation and the onset of the electrophysiologic effects of antiarrhythmic drugs in humans. The myocardial uptake and pharmacodynamics of the antiarrhythmic drug, procainamide, were studied during i.v. infusion in nine patients with ventricular tachycardia undergoing electrophysiologic study. Myocardial procainamide uptake was determined by serial measurements of arterial-coronary sinus drug concentration differences and measurement of coronary sinus blood flow during a 50-min procainamide infusion. The myocardial uptake of procainamide was 10 +/- 4% (mean +/- S.D.) of the total dose at 50 min. Coronary sinus procainamide concentrations equilibrated with arterial concentrations within 30 min of the start of the infusion. However, peripheral venous procainamide concentrations did not reach equilibrium with the arterial compartment during the 50-min drug infusion. Changes in the QRS duration, ventricular conduction time, QTc and ventricular refractory periods correlated in a linear fashion with changes in the plasma procainamide concentrations. The slopes of the arterial and coronary sinus concentration-effect relationships were similar and significantly greater than the slopes of the peripheral venous concentration-effect relationships (P < .05). Thus, procainamide equilibrates rapidly, but not instantaneously, in the myocardium. Short-term electrophysiologic effects correlate best with the arterial and coronary sinus drug concentrations. During this period, venous procainamide concentrations do not accurately reflect the myocardial concentration, effects or the eventual steady-state relationships. PMID- 8355179 TI - A decomposition product of a contaminant implicated in L-tryptophan eosinophilia myalgia syndrome affects spinal cord neuronal cell death and survival through stereospecific, maturation and partly interleukin-1-dependent mechanisms. AB - The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall of 1989. The neuropathic clinical features in L-TRP EMS are complex and mixed. In the present study, one of the impurities most highly associated with development of L-TRP EMS, 1,1'-ethylidenebis[L-tryptophan] (EBT), and two of its diastereoisomeric breakdown products, were compared for evidence of neurotoxicity in vitro. In 1-month-old spinal cord cultures derived from fetal mice, synthetic (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1S-beta C) produced a 30 to 35% loss in numbers of neurons. Toxicity was not apparent after treatment with the R-isomer of the same compound or with the parent compound, EBT. Cotreatment of cultures with 1S-beta-C and neutralizing antiserum to interleukin-1 alpha (IL-1 alpha), or with 1S-beta-C and neutralizing antiserum against the murine IL-1 receptor, prevented neuronal cell death associated with 1S-beta-C. Recombinant IL-1 alpha also produced neuronal killing that was not additive to that observed with the 1S-beta-C treatment. In contrast, in immature spinal cord neuronal cultures, the 1S-beta-C, but not the 1R-beta-C or EBT, prevented the 30% cell death which normally occurs in these cultures. Neither neutralizing anti-IL-1 antibody, nor anti-IL-1 receptor antibody blocked the neuronal survival effect, suggesting that 1S-beta-C induces neuronal survival through a receptor-mediated mechanism independent of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355180 TI - Elucidation of a specific binding site for angiotensin II(3-8), angiotensin IV, in mammalian heart membranes. AB - Data are presented describing a new angiotensin binding site in rabbit and guinea pig heart, distinct from AT1 and AT2, that demonstrates high specificity and affinity for the hexapeptide fragment angiotensin II(3-8), which will be referred to here as angiotensin IV (AIV). Equilibrium binding in rabbit heart membranes was achieved in 2 hr at 37 degrees C and produced a calculated kinetic KD of .174 +/- .018 nM. Saturation equilibrium binding data for rabbit and guinea pig heart were best fit to a one-site model with Hill coefficients near unity. Guinea pig membranes exhibited a KD = 1.33 +/- .02 nM and a Bmax = 144 +/- 19 fmol/mg protein, and rabbit heart membranes had a KD = 1.70 +/- .50 nM and a Bmax = 731 +/- 163 fmol/mg protein. The binding site showed a high specificity for AIV, although it exhibited low affinity for angiotensin II, angiotensin III, Sar1,Ile8 angiotensin II, DuP 753, CGP42112A and PD123177. A large number of nonangiotensin related peptides were unable to compete effectively for 125I-AIV binding. Deletions made from the C-terminal end of AIV caused a decrease in affinity: AIV > AII(3-7) >> AII(3-6) >> AII(3-5). Extension of the C-terminal end of AIV corresponding to the amino acids of human angiotensinogen caused little change in affinity. GTP gamma S had no effect on binding, suggesting non-G protein linkage. Binding was widely distributed throughout the heart; it was observed on cardiocytes and blood vessels as well as in the epicardium and the endocardium. PMID- 8355181 TI - Fluoro-gold and pentamidine inhibit the in vitro and in vivo release of dopamine in the striatum of rat. AB - Fluoro-Gold (FG), first developed as an antifungal/antiparasitic agent, is now also used extensively as a retrograde tracer in histological studies of nervous tissue. The fact that FG is taken up by dopamine (DA) terminals before its retrograde transport to DA cell bodies implies a presynaptic interaction, though the biochemical target(s) and mechanism(s) are unknown. To further elucidate, FG and another aromatic diamidine, pentamidine, were tested on [3H]DA release and uptake in vitro from striatal slices and synaptosomes. Neither compound affected [3H]DA uptake in synaptosomes and slices, and neither inhibited DA efflux mediated through reversal of DA uptake mechanisms. NMDA-mediated glutamate-evoked DA release was completely inhibited by either FG (IC50 approximately 3 microM) or pentamidine (IC50 approximately 1 microM), and 20 mM K(+)-evoked DA release was inhibited by similar concentrations but only to 60% of control. Arginine (up to 500 microM) and spermidine (200 microM) failed to reverse 33 microM FG inhibition of either the spontaneous or the glutamate-evoked DA release, indicating that FG inhibition of release was not necessarily via blockade of either nitric oxide generation or spermidine binding to NMDA receptors. Interestingly, FG (33 microM) and pentamidine (10 microM) inhibited 1 and 5 microM D-methamphetamine (METH) evoked [3H]DA release to approximately 50% of control, and in striatal synaptosomes, FG (33 microM) and pentamidine (10 microM) inhibited 5 microM METH- and 1.25 mM Ca(++)-evoked DA release. Additionally, in vivo brain microdialysis supported the in vitro results; 100 microM FG in the microdialysis buffer inhibited 70% of the increase in extracellular DA in the striatum produced by 2.5 mg/kg METH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355182 TI - Electrophysiological effects of cocaine in the rat nucleus accumbens: microiontophoretic studies. AB - The nucleus accumbens (NAc) is intricately involved in maintaining cocaine self administration. Cocaine inhibits the firing of most NAc cells due to its ability to prevent the reuptake of dopamine (DA) and 5-hydroxytryptamine (5-HT), both of which predominantly inhibit NAc cell discharge in vivo. The present studies investigated the roles of DA and 5-HT in the effects of iontophoretically applied cocaine. Most NAc cells exhibited negative/positive waveforms (Type I cells). These cells were significantly more sensitive to cocaine than Type II cells (positive/negative waveforms), apparently due to differences in the actions of 5 HT. Whereas DA was equipotent at inhibiting Type I and Type II cells, 5-HT inhibited Type I cells but, primarily excited Type II cells. Thus the ability of cocaine to potentiate the effects of both DA and 5-HT resulted in a pronounced inhibition of Type I cells, whereas the 5-HT-mediated excitation of Type II cells appeared to reduce DA-mediated inhibition. Combined administration of selective DA (GBR 12909) and 5-HT (fluoxetine) uptake inhibitors was required to mimic the effects of cocaine on Type I and Type II NAc cells. Acute depletion of DA (86%) produced by alpha-methyl-p-tyrosine (AMPT) significantly reduced the inhibitory effects of cocaine on all NAc cells. Acute depletion of 5-HT (74%) produced by p chlorophenylalanine (PCPA) significantly reduced the inhibitory effect of cocaine on Type I cells, but it significantly enhanced the inhibition of Type II cells. Simultaneous reduction of DA and 5-HT levels produced a significantly greater reduction of cocaine-induced inhibition of Type I neurons than did AMPT or PCPA alone. These findings are discussed in relation to proposed roles of DA and 5-HT in cocaine self-administration. PMID- 8355184 TI - Rapamycin, a potential disease-modifying antiarthritic drug. AB - Rapamycin (RAPA), a potent immunosuppressive agent that prevents organ graft rejection in animal models of transplantation, possesses a mechanism of action different than that of cyclosporin A and FK-506. In this study, the pharmacological activity of RAPA in a variety of immune and inflammatory models was assessed in order to define better its potential utility as an antiarthritic agent. RAPA inhibited T cell-mediated inflammation in mouse methylated bovine serum albumin-induced delayed-type hypersensitivity (ED40 = 4.7 mg/kg p.o.) and produced oral ED50 of 2.0 mg/kg against developing adjuvant arthritis in rats (3 day dosing schedule) and 9.5 mg/kg in established adjuvant arthritis in rats (daily dosing schedule). In both models of adjuvant arthritis, effects of RAPA were maintained even after cessation of drug dosing. In contrast, after discontinuation of cyclosporin A (5- and 10-mg/kg doses), disease activity returned. RAPA was also effective in another T cell-mediated model, experimental allergic encephalomyelitis (ED50 approximately 5 mg/kg p.o.). At higher doses, RAPA significantly inhibited carrageenan paw edema in rats, a model of acute inflammation (ED40, 56 mg/kg p.o.), without increasing serum corticosterone levels. In this model, doses approximately 10 to 20 times greater than active doses in T cell-mediated models were required. RAPA at 1 to 50 microM did not inhibit in vitro human synovial phospholipase A2 or 5-lipoxygenase and cyclo oxygenase activity in the human blood leukocyte assay. The total profile of RAPA suggests that it may be effective in the treatment of rheumatoid arthritis, multiple sclerosis and other autoimmune diseases. PMID- 8355183 TI - Atherosclerosis-related remodeling of aortic relaxation to purines in the Watanabe heritable hyperlipidemic rabbit. AB - The mechanism of the unimpaired relaxant effect of ATP in the Watanabe heritable hyperlipidemic rabbit aorta was investigated to elucidate the involvement of P2y purinoceptor at the endothelial level during atherosclerosis. Experiments were carried out on isolated thoracic aorta from such rabbits that were 12 months of age. The potent P2y purinoceptor agonist, 2-methylthio-ATP, did not induce any endothelium- or smooth muscle-dependent relaxation, thus excluding any involvement by the P2y purinoceptor. ADP, but not AMP, produced relaxation of the aorta by acting at both endothelial and smooth muscle levels. Adenosine relaxed the vessel by acting only in smooth muscle. The maintained endothelial relaxant effect of ATP and ADP is therefore not due to activation of P1 or P2y purinoceptors but may involve activation of a remodeled purinergic receptor site that emerges with the progression of atherosclerosis. This site is antagonized by methylene blue. The disorganization of the endothelial monolayer observed in the morphological analysis may be related to functional remodeling of the endothelial purinergic activity in atherosclerosis. PMID- 8355185 TI - Effects of the selective sigma receptor ligand, 6-[6-(4 hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), on behavioral and toxic effects of cocaine. AB - Certain sigma receptor ligands have been shown to block locomotor stimulation produced by cocaine at doses that do not have significant behavioral activity when given alone. Using a potent and selective ligand of sigma binding sites, 6 [6-(4-hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), we further investigated the influence of sigma ligands on additional behavioral and toxic effects of cocaine in mice. A behaviorally inactive dose of NPC 16377 shifted the dose-effect function for the locomotor stimulant effects of cocaine to the right by a factor of 2.5. A higher dose of NPC 16377 produced an insurmountable blockade of this stimulant effect of cocaine. Prior exposure to cocaine enhances the locomotor stimulant effects of cocaine (sensitization). NPC 16377 prevented the development of cocaine sensitization without producing behavioral effects of its own. However, NPC 16377 was unable to block the expression of sensitization in mice previously exposed to cocaine. NPC 16377 also did not consistently alter the discriminative stimulus effects of cocaine or methamphetamine in rats discriminating either 3 or 10 mg/kg of cocaine, or 1 mg/kg of methamphetamine from saline. The potential phencyclidine-like behavioral effects of NPC 16377 were also evaluated. Unlike the NMDA channel ligand, dizocilpine, NPC 16377 did not increase responding under a fixed-interval schedule of food presentation in rats nor did it substitute for the discriminative stimulus effects of either 1.5 mg/kg of phencyclidine or 0.2 mg/kg of dizocilpine in rats discriminating these drugs from saline. NPC 16377 displayed limited but significant anticonvulsant activity against diazepam-sensitive cocaine convulsions. The lethal effects of higher doses of cocaine were neither significantly blocked nor enhanced in rats or mice with NPC 16377. These findings extend earlier observations on the cocaine blocking effects of sigma ligands to a novel structure with exceptional selectivity for sigma sites. These data indicate that some sigma ligands may be capable of altering certain behavioral and toxic actions of cocaine without notable behavioral side effects as evidenced in preclinical tests. As such, these compounds may ultimately be useful in the treatment of cocaine abuse. PMID- 8355186 TI - Effect of protein binding on 4-methylumbelliferyl sulfate desulfation kinetics in perfused rat liver. AB - 4-Methylumbelliferyl sulfate (4MUS), a polar metabolite of 4-methylumbelliferone (4MU), is known to undergo desulfation and participate in futile cycling with 4MU. Unusual parabolic or increasing profiles of the steady-state extraction ratio (Ess) of 4MUS with respect to concentration in rat livers perfused with a red cell (20%)-albumin (1%) medium have been reported (Ratna et al., 1993). In order to study this unusual phenomenon, we examined the desulfation of 4MUS in the single-pass rat liver in the absence of albumin. We further employed a tubular-flow model to describe the present observations and data previously obtained on 4MUS in order to predict the effects of protein binding and enzymatic constants for conjugation/deconjugation on the hepatic processing of 4MUS and its metabolites. The net hepatic extraction ratio from albumin-free perfusate decreased from 0.465 to 0.326 when the 4MUS input concentration was increased from 122 to 908 microM; moreover, the unusual profiles previously observed for ESS with increasing concentration in albumin-containing perfusate were not apparent. The hepatic clearances and desulfation rates of 4MUS were essentially identical to those observed in the presence of albumin, when the latter were expressed in terms of unbound concentrations (unbound input and logarithmic average unbound concentration of the input and output blood). Initial modeling indicated that first nonlinear protein binding (dissociation constant KD of 93 microM) and then saturable desulfation (Km of 382 microM) were responsible for the unusual increasing and then decreasing trend of ESS with concentration in the presence of albumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355187 TI - The in vivo antiplatelet effects of thromboxane A2 synthase inhibitors are potentiated by simultaneous thromboxane A2/prostaglandin H2 receptor blockade. AB - The aim of the present study was twofold: 1) to assess whether inhibition of thromboxane A2 (TxA2) synthase exerts more potent antiplatelet effects when applied concomitantly with TxA2 and prostaglandin (PG)H2 receptor blockade and 2) whether these effects are mediated through redirection of PG endoperoxides toward the synthesis of antiplatelet PGs, such as PGI2 and PGE2. Thus, cyclic flow variations (CFVs), due to recurrent platelet aggregation, were initiated in the stenotic, endothelially injured carotid arteries of 39 rabbits. After 30 min of CFVs, the animals received: 1) SQ29548 (up to 0.6 mg/kg bolus + 0.2 mg kg-1 hr-1, n = 13), a TxA2/PGH2 receptor antagonist; 2) dazoxiben (up to 15 mg/kg bolus + 5 mg kg-1 hr-1, n = 13), a TxA2 synthase inhibitor and 3) picotamide (up to 20 mg/kg bolus + 20 mg kg-1 hr-1, n = 13), a drug with simultaneous TxA2 synthase and receptor blocking properties. CFVs were abolished in 6, 7, and 12 animals treated with SQ29548, dazoxiben, and picotamide, respectively (P < .01 for picotamide versus SQ29548 and dazoxiben). The animals in which CFVs were not abolished by SQ29548 or dazoxiben received the other drug at the same dose. CFVs were abolished by dazoxiben in five of seven rabbits that initially did not respond to SQ29548 and by SQ29548 in five of six animals that did not respond to dazoxiben. All animals that responded to the combination of SQ29548 and dazoxiben, as well as those that responded to picotamide, received increasing intravenous infusions of epinephrine to restore CFVs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355188 TI - Apparent mediation of the stimulus properties of a low dose of quinpirole by dopaminergic autoreceptors. AB - This study examined the hypothesis that, if the stimulus properties of the D2 agonist quinpirole (QUIN) were mediated by autoreceptors, then pharmacological treatments engendering a decline in dopamine (DA) release and consequent decrease in postsynaptic DA receptor stimulation should result in QUIN-appropriate responding; those that activate postsynaptic receptors should result in saline appropriate responding. In rats trained to discriminate 0.05 mg/kg of QUIN from saline using standard operant drug discrimination procedures, QUIN (up to the training dose), two other putative D2 autoreceptor agonists (low-dose apomorphine and N-propylnorapomorphine), the DA depeleter alpha-methyl-p-tyrosine (AMPT) and the D1 antagonist SCH 23390 all produced primarily QUIN-lever responding. Moreover, coadministration of alpha-methyl-p-tyrosine with QUIN potentiated QUIN stimulus properties. Higher doses of apomorphine, known to stimulate postsynaptic D1 and D2 receptors and pretreatment with the D2 antagonist haloperidol decreased QUIN-lever responding. Neither the D1 agonist SKF38393, the indirect D1/D2 agonist d-amphetamine, the D2 antagonist haloperidol or coadministration of SCH 23390 and d-amphetamine substituted for QUIN. Coadministration of either SKF 38393 or d-amphetamine with QUIN decreased levels of QUIN responding. Taken together, the data are consistent with the contention that the stimulus properties of 0.05 mg/kg of QUIN are primarily mediated by D2-type presynaptic autoreceptors and that these stimulus properties involve a decline in DA release and consequent decreased postsynaptic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355189 TI - RS 42358-197, a novel and potent 5-HT3 receptor antagonist, in vitro and in vivo. AB - The pharmacological activity of RS 42358-197, a novel 5-HT3 receptor antagonist has been evaluated in vitro and in vivo. In functional experiments in vitro, RS 42358-197 behaved as a competitive antagonist against 5-HT-induced contractions in the guinea pig ileum (low-potency phase), yielding a pA2 estimate of 8.1. RS 42358-197 was devoid of any agonistic or antagonistic activity at 5-HT1-like receptors (contraction of canine saphenous vein), 5-HT2 receptors (contraction of rabbit aorta) or 5-HT4 receptors (contraction of guinea pig ileum, high-potency phase). RS 42358-197 failed to affect the concentration-effect curve to substance P in guinea pig ileum. In anesthetized rats. RS 42358-197, administered by the intravenous, intraduodenal or transdermal route, dose-dependently inhibited the Bezold-Jarisch reflex induced by 2-methyl 5-HT (ID50:0.05 micrograms/kg; i.v., 5.7 micrograms/kg; i.d., and 11.6 micrograms/chamber, respectively). In this regard, when administered intraduodenally, RS 42358-197 was more potent and exhibited a longer duration of action than either ondansetron or granisetron. In dogs, RS 42358-197, administered either intravenously or orally, dose-dependently inhibited the emesis induced by cisplatin, actinomycin and cyclophosphamide, but not that induced by apomorphine. When tested at maximally effective doses against cisplatin-induced emesis in dogs, RS 42358-197 had a longer duration of antiemetic activity (> 6 h) than ondansetron (2 h). RS 42358-197, administered orally, also afforded protection against cisplatin-induced emesis in ferrets. At doses that showed marked anti-emetic activity in dogs (10-100 micrograms/kg; i.v. and 100-1000 micrograms/kg; i.d.), RS 42358-197 did not produce any hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355190 TI - Role of the hydrophobic face of amphipathic alpha-helical peptides in synthetic pulmonary surfactants. AB - The sequence requirements for the peptide component of a totally synthetic lung surfactant mixture were examined. A series of model amphipathic alpha-helical peptides (MAP) with six to 18 residues were synthesized by solid phase techniques, mixed with dipalmitoylphosphatidylcholine (DPPC) and tested for efficacy in an in vitro adult rat lung model. The most effective peptide in these mixtures contained 10 residues. Peptides containing eight and 14 residues were also highly active when mixed with DPPC in buffer, but a six-residue peptide was inactive. Longer peptides were active only when mixed with DPPC in trifluoroethanol before swelling in buffer; no other lipids were required to elicit high activity. Biologically effective peptides, when combined with DPPC, formed translucent mixtures that were significantly less turbid than ineffective mixtures, dramatically decreased the enthalpy of the main phase transition of DPPC and reduced the gamma min in the pulsating bubble surfactometer. Turbidity and minimal surface tensions were significantly correlated with activity in this series of peptides. These data show that effective synthetic lung surfactants may be prepared with mixtures of DPPC and idealized amphipathic alpha-helical peptides containing as few as eight to 10 residues. They lend further support to the hypothesis that amphipathic alpha-helical peptides with hydrophobic surface areas greater than approximately 6.5 nm2 in simple mixtures with DPPC are biologically active. PMID- 8355191 TI - Effects of the putative polyamine antagonists diethylenetriamine and 1,10 diaminodecane on N-methyl-D-aspartic acid-stimulated [3H]norepinephrine release from rat hippocampal slices. AB - N-Methyl-D-aspartic acid (NMDA, 500 microM) stimulated the net release of [3H]norepinephrine from rat hippocampal slices. The putative polyamine inverse agonist 1,10-diaminodecane (DA10) dose-dependently inhibited NMDA-stimulated release with a calculated IC50 value of 33 microM. The putative polyamine competitive antagonist diethylenetriamine (DET) partially inhibited (maximum effect 40%) NMDA-stimulated release at 1 mM which was the highest concentration tested. DET (1 mM) but not DA10 also partially inhibited potassium-stimulated release of norepinephrine from hippocampal slices. Neither DET or DA10 significantly altered the nonstimulated basal efflux of neurotransmitter. The inhibition of NMDA-stimulated release produced by 100 microM DA10 or 1 mM DET was not attenuated by addition of the polyamines spermine or spermidine up to 1 mM. In addition, the IC50 value for DA10-induced inhibition of NMDA-stimulated neurotransmitter release was not altered by the addition of DET (100-1000 microM). The combination of the glycine antagonist 7-chlorokynurenic acid (3 microM) and DA10 (100 microM) inhibited NMDA-stimulated release by approximately 70%. The addition of the glycine agonist D-serine (3-100 microM) partially attenuated the inhibition produced by these two compounds. No further enhancement was observed when D-serine was added in the presence of spermine or spermidine. Finally, the NMDA open channel blocker (+)-5-methyl-10,11- dihydro-5H dibenzo[1,d]cyclo-hepten-5,10-imine maleate dose-dependently inhibited NMDA stimulated release with an IC50 value of 25 nM. The inhibitory potency of (+)-5 methyl-10,11- dihydro-5H-dibenzo[1,d]cyclo-hepten-5,10-imine maleate was not significantly altered by the presence of either DET (100 microM) or DA10 (30 or 100 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355192 TI - Discriminative stimulus properties of cocaine in relation to dopamine D2 receptor function in rats. AB - Previous studies indicate that the discriminative stimulus effects of cocaine are mediated predominantly by indirect activation of dopamine (DA) D2 postsynaptic receptors, although DA D1 receptors may also be involved. In the present study, full or partial D2 agonists and D2 antagonists were tested for their ability to substitute for, potentiate or antagonize the stimulus effects of cocaine in rats (n = 15) trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced task. The full D2 agonists bromocriptine (1.25-20 mg/kg) and quinpirole (0.013-0.2 mg/kg) engendered substantial cocaine-lever responding (> 80% drug-lever responding), whereas the partial D2 agonists preclamol (2.5-10 mg/kg) and terguride (0.313-1.25 mg/kg) produced less than 50% cocaine-lever responding. Co-administration of a threshold dose of cocaine (1.25 mg/kg) with low doses of bromocriptine (1.25-5 mg/kg) or quinpirole (0.025-0.1 mg/kg) induced higher percentages of cocaine-lever responding as compared with occasions when these D2 agonists were given alone. However, co-administration of this dose of cocaine with preclamol (2.5-10 mg/kg) or terguride (0.313-1.25 mg/kg) did not alter the percentage of cocaine-lever responding observed when these partial D2 agonists were administered alone. Pretreatment with the D2 antagonists bromuride (0.25-1 mg/kg) and haloperidol (0.125-0.5 mg/kg) significantly reduced the percentage of cocaine-lever responding. Preclamol (0.625-10 mg/kg) and terguride (0.019-5 mg/kg), but not bromocriptine (2.5-20 mg/kg) or quinpirole (0.01-0.08 mg/kg), significantly reduced the percentage of cocaine-lever responding. These results suggest that full D2 agonists substitute completely for cocaine, whereas partial D2 agonists do not produce cocaine-like responding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355193 TI - Further biological activities of the novel choline analogs selenonium choline and acetylselenonium choline. AB - The pharmacological actions of the novel choline analog, selenonium choline [(CH3)2Se+CH2CH2OH] and its acetyl ester acetylselenonium choline (ASeCh) were studied in vivo and in vitro. ASeCh produced a dose-related decrease in mean arterial pressure in the rat similar to acetylcholine (ACh) but was 1% to 2% as potent. ASeCh demonstrated agonist activity on the rat isolated ileum and was approximately 2% as active as ACh. Selenonium chlorine (SeCh) was taken up and acetylated in brain tissue slices in a time- and concentration-dependent manner. The use of KCl as a loading stimulus did not increase the uptake of SeCh but increased tissue levels of ASeCh 1.5-fold over the control concentrations. The uptake of SeCh was described by a single low-affinity uptake component (Km = 167 microM) that was not blocked by hemicholinium-3. In contrast, hemicholinium significantly blocked the acetylation of SeCh. Compared with basal release, depolarization with KCl caused a significant release of ASeCh into the incubation medium. A neural specificity was suggested for the in vitro uptake of SeCh. Acetylation of SeCh in vivo in the rat after intraventricular administration was similar to the extent of acetylation of [2H4]-choline. ASeCh bound to both M1 and M2 cholinergic receptors with 2% to 3% of the affinity observed for ACh. These data suggest that SeCh may satisfy criteria for a false neurotransmitter precursor. PMID- 8355194 TI - Selective potentiation by an A1 adenosine receptor enhancer of the negative dromotropic action of adenosine in the guinea pig heart. AB - The drug (2-amino-4,5-dimethyl-3-thienyl)-[3(trifluoromethyl)-phenyl]methanone (PD 81,723) has been shown to enhance allosterically A1 adenosine receptor binding in brain membranes. The objective of this study was to determine the specificity and selectivity (A1 versus A2) of PD 81,723 as an enhancer of the negative dromotropic effect of exogenous adenosine in guinea pig isolated and in situ hearts. In isolated hearts, PD 81,723 alone produced only a small stimulus to His bundle (S-H) interval prolongation of 1.5 to 4 msec, which was completely reversed by the A1 adenosine receptor antagonist 8-cyclopentyltheophylline and adenosine deaminase. PD 81,723 (5 microM) significantly decreased the EC50 value of adenosine for prolongation of the S-H interval from 6.7 +/- 0.6 to 4.4 +/- 0.5 microM. The potentiation of the negative dromotropic effect of adenosine by PD 81,723 was dose dependent, i.e., 5 and 10 microM PD 81,723 enhanced the maximal S H interval prolongation caused by 3 microM adenosine by 207% and 609%, respectively. In contrast, the same concentration of PD 81,723 had no effect on either the S-H interval prolongation caused by carbachol or MgCl2 or the coronary vasodilatory effect of adenosine. In in situ hearts, PD (2 mumol/kg i.v.) alone caused only a small but not significant negative dromotropic effect, increasing the atrium to His interval from 58 +/- 2 to 61 +/- 1 msec. However, the same dose of PD 81,723 caused a significant leftward and upward shift of the adenosine dose response curve for inducing atrium to His bundle interval prolongation and increased the degree of atrioventricular block caused by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355195 TI - Potency of 5-hydroxytryptamine1a agonists to inhibit adenylyl cyclase activity is a function of affinity for the "low-affinity" state of [3H]8-hydroxy-N,N dipropylaminotetralin ([3H]8-OH-DPAT) binding. AB - In this study, the radiolabeled 5-hydroxytryptamine1A agonist, [3H]8-hydroxy-N,N dipropylamino tetralin ([3H]8-OH-DPAT), was shown to have both a high (Kd, 0.7 +/ 0.2 nM) and a low (Kd, 17 +/- 4 nM) affinity binding component in rat hippocampal homogenate preparations in the absence of guanine nucleotides. The high-affinity binding component was markedly reduced by the elimination of Mg++ from the incubation medium and the addition of both the nonhydrolyzable guanine nucleotide guanylylimidodiphosphate (Gpp(NH)p) (100 microM) and 1.0 mM EDTA to the incubation medium. Under these latter conditions, a single binding affinity component was observed with a Kd of 11 +/- 1 nM, a value in good agreement with the value for the low-affinity component measured in the absence of Gpp(NH)p. Further, the Bmax value for the single low-affinity binding component measured in the presence of Gpp(NH)p was essentially equivalent to the total of the two Bmax values found in the absence of Gpp(NH)p. A binding assay was developed using 15 nM [3H]8-OH-DPAT to determine the affinities of serotonergic drugs for the low affinity component of [3H]8-OH-DPAT binding and these values were compared with their affinities for the high-affinity binding component as well as their potencies in a hippocampal adenylyl cyclase assay. For agonists, the Ki value for the high-affinity binding component was always less than the low-affinity Ki value, whereas the antagonist spiperone had similar values for both the high affinity and low-affinity binding components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355196 TI - Effect of some products of protein catabolism on the endothelium-dependent and independent relaxation of rabbit thoracic aorta rings. AB - We have investigated the effect that some products of protein catabolism have on endothelium-dependent and -independent relaxation of rabbit aorta rings precontracted with phenylephrine (PE). All the products tested, i.e., creatinine (CRT), guanidinosuccinic acid (GSA), urea (UR), guanidine (GND) and methylguanidine (MG), are structurally related to L-arginine (L-ARG), the substrate for nitric oxide (NO) biosynthesis which accounts for the biological properties of endothelium-derived relaxing factor (EDRF). Endothelium-derived NO (EDNO) release was induced by agents acting via a receptor- [acetylcholine (ACh)] or a nonreceptor-mediated mechanism (calcium ionophore A23187), and the endothelial-independent relaxation was induced by the NO donor glyceryl trinitrate (GTN). CRT (0.1-10 mM) did not modify the endothelium-dependent relaxation caused by ACh or A23187 but produced a small increase in the response to the endothelium-independent vasorelaxant GTN. Concentrations of GSA up to 1 mM did not affect the relaxation of rabbit aortic rings induced by either ACh or A23187, but at 10 mM, GSA enhanced the relaxation produced by these agents. UR (1 100 mM) inhibited, in a concentration-dependent manner, the relaxation induced by ACh, but not that caused by A23187 or GTN. By comparison, GND and MG (0.1-10 mM) produced a concentration-related inhibition of both ACh- and A23187-induced relaxation. The inhibition by these compounds was either completely or partially reversed by L-ARG. In contrast, the relaxation induced by GTN was inhibited only by higher concentrations (10 mM) of GND or MG. These results indicate that some products of protein catabolism can reduce EDNO formation in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355197 TI - Alterations in vascular structure and function after short-term losartan treatment in spontaneously hypertensive rats. AB - The current study was performed to investigate the effects of a 2-week treatment regimen with either hydralazine or the nonpeptide angiotensin II subtype 1 receptor antagonist losartan (both at 10 mg/kg daily s.c. injection) on blood pressure and vascular smooth muscle function and structure in male spontaneously hypertensive rats with established hypertension (24 weeks of age; systolic blood pressure = 174 +/- 7 mm Hg). Systolic blood pressure and body weight were recorded before and once weekly after initiation of treatment. Mean arterial pressure, heart rate and heart weight were determined and experiments were conducted to assess changes in vascular reactivity and arterial medial thickness in ring segments of aorta and tail artery at the end of the treatment period. Systolic blood pressure, as well as mean arterial pressure, were significantly decreased to normotensive levels in hypertensive rats after 2 weeks of either hydralazine or losartan treatment. No effect on heart rate was observed in response to either antihypertensive agent. Body weight was not affected in either of the treatment groups, but a significant decrease in artery ring weight, arterial medial thickness and heart weight was seen only in losartan-treated rats. Whereas no changes in vascular reactivity were seen in hypertensive rats receiving hydralazine, norepinephrine- and serotonin-induced contractions were attenuated and acetylcholine-induced relaxations were enhanced in the losartan treated rats. These data demonstrate that, although short-term 2-week treatment with either hydralazine or losartan results in normalization of blood pressure, only losartan resulted in significant alterations in vascular function and structure in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355198 TI - Ontogenic differences in the inhibition of gastric acid secretion by epidermal growth factor. AB - Gastric secretions were studied in rats by pyloric ligation in vivo. The effects of epidermal growth factor (EGF) administered s.c. on gastric secretion were evaluated at different stages of development (8, 14, 20 and 30 postnatal days). The rates of fluid, protein and acid outputs were very low in developing rats but increased in maturing rats. The rate of acid output in 8- day-old rats (3.83 +/- 1.16) was not different from that in 14-day-old rats (4.84 +/- 0.99), whereas the rate of acid output in 20-day-old rats was 11-fold greater than that in 14-day old rats, and it was 21-fold greater in 30-day-old rats. Subcutaneous administration of 30 micrograms/kg b.wt. of EGF significantly suppressed the gastric secretion of fluid, protein and acid in 20- and 30-day-old rats. In 30 day-old rats, acid output was 85% lower at 1 hr after EGF administration and in 20-day-old rats it was 85% lower at 2 hr and 50% lower at 3 hr. Interestingly, EGF had no effect on basal gastric secretions in 8- and 14-day-old rats; EGF also had no effect on the gastric acid output that was stimulated by pentagastrin administration in 14-day-old rats. In 20-day-old rats, inhibitory effects of EGF lasted for 3 hr before gastric secretions rebounded to normal levels, but inhibition lasted for only 1 hr in 30-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355199 TI - 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydrochloride (U-37883A): pharmacological characterization of a novel antagonist of vascular ATP-sensitive K+ channel openers. AB - This study describes the in vitro and in vivo characteristics of a guanidine 4 morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl-hydroc hloride (U-37883A), as an antagonist of vascular ATP-sensitive K+ channels (KATP). In isolated rabbit mesenteric artery, the antagonistic effects of U-37883A (0.5-5 microM) were studied against vasorelaxation produced by cromakalim (0.5 microM), minoxidil sulfate (5 microM), pinacidil (1 microM) and RP-49356 (1 microM). The dose response curves for U-37883A against all four potassium channel openers were similar with U-37883A, IC50S ranging from 0.78 to 1.4 microM, suggesting that U 37883A is producing inhibition by acting at a step that is common to all four potassium channel openers during their activation of the vascular KATP. In contrast, U-37883A at 10 microM did not inhibit relaxation dose-response curves by nitroglycerine, forskolin or D600. U-37883A (1 or 10 microM) effectively inhibited as well as reversed 42K efflux-stimulated by cromakalim (1 microM) or minoxidil sulfate (5 microM). Finally, U-37883A (3 mg/kg i.v.) was found to inhibit significantly as well as reverse hypotension produced by minoxidil (1 mg/kg i.v. or 3 mg/kg p.o.), cromakalim (0.5 mg/kg p.o.) and pinacidil (0.3 mg/kg i.v.) in rats, cats and dogs. In contrast, the in vivo responses to phenylephrine, nitroglycerine, sodium nitroprusside or isoproterenol were not altered. U-37883A thus appears to be the first nonsulfonylurea shown to block consistently and selectively the in vitro as well as the in vivo pharmacological responses to various potassium channel openers. This structurally novel KATP antagonist therefore would be useful for further characterizing the mechanisms of pharmacological modulation of the KATP in a variety of cell systems. PMID- 8355200 TI - Vanilloid (capsaicin) receptor in the rat: positive cooperativity of resiniferatoxin binding and its modulation by reduction and oxidation. AB - Specific [3H]resiniferatoxin (RTX) binding is thought to represent the postulated vanilloid (capsaicin) receptor. In the present report, this binding has been reevaluated using a modified [3H] RTX binding assay in which the high nonspecific binding, which limited the previous characterization, was reduced by adding alpha 1-acid glycoprotein, a plasma protein that binds RTX, to the usual binding assay after RTX binding by the vanilloid receptor had been terminated. Specific [3H]RTX binding by both dorsal root ganglion (DRG) and spinal cord membranes of the rat followed sigmoidal saturation kinetics indicating apparent positive cooperativity. The cooperativity index determined by fitting the data to the Hill equation was 1.7 in DRG and 1.9 in spinal cord. Apparent dissociation constants were estimated as 24 pM for DRG and 11 pM for spinal cord preparations. As predicted by the modified Hill equation, at low receptor occupancy nonradioactive agonists (RTX, tinyatoxin, capsaicin) produced biphasic competition curves. The initial (enhancement) phase of these curves correlated with the biological potency of the agonist. Dithiothreitol reduced both positive cooperativity and apparent binding affinity; the oxidizing agent 5,5'-dithiobis-(2-nitrobenzoic acid) reduced the cooperativity index without a major effect on binding affinity. These findings suggest that the vanilloid receptor is a receptor cluster in which the subunits cooperate; cooperation is, at least in part, subject to redox modulation. PMID- 8355201 TI - Purine nucleoside phosphorylase inhibitors: biochemical and pharmacological studies with 9-benzyl-9-deazaguanine and related compounds. AB - Certain derivatives of 9-deazaguanine that contain arylmethyl, heteroarylmethyl or cycloalkylmethyl groups at the 9-position are potent inhibitors of purine nucleoside phosphorylase (PNP, E.C. 2.4.2.1). To determine whether these agents can produce metabolically significant inhibition of PNP in cells and in animals, the authors performed pharmacological studies with a representative member of the series, 9-benzyl-9-deazaguanine (BzDAG). BzDAG was a potent inhibitor of PNP from calf spleen (Ki = 12 nM). It was also an effective inhibitor of PNP in cells and in animals as shown by the findings that it 1) inhibited the conversion of inosine to nucleotides in L1210 cells in culture at concentrations that had little effect on the utilization of hypoxanthine; 2) potentiated the toxicity of deoxyguanosine to CCRF-CEM cells in culture; 3) increased the pools of deoxy GTP in CCRF-CEM, Molt-3 and Molt-4 cells that had been treated with deoxyguanosine; 4) prevented the toxicity of 6-thioguanosine to HEp-2 cells in culture; 5) increased the plasma levels of endogenous inosine in rats; and 6) increased the plasma levels of 2',3'-dideoxyinosine in rats that had received BzDAG and dideoxyinosine in combination. Pharmacokinetic analysis of BzDAG in the rat showed it to be 48% orally bioavailable (at a dose of 5 mg/kg). About 95% of BzDAG was protein bound. After i.v. administration of BzDAG (5 mg/kg), more than 50% of the erythrocyte PNP was inhibited for 40 min. These results indicate that the 9-substituted-9-deazaguanines are potent orally active PNP inhibitors and are therefore of potential clinical interest as immunosuppressive and anti inflammatory agents. PMID- 8355202 TI - Human hepatic cytochrome P450 2D6-like activity in nonhuman primates: catalytic characterization in vitro. AB - Previous studies have identified the monkey as an animal model for the genetic polymorphism affecting human hepatic cytochrome P450 2D6 enzyme. However, contrary to an earlier in vivo observation, the present study failed to find evidence of polymorphism of this enzyme activity in liver preparations of 84 African green (Cercopithecus aethiops) monkeys. The kinetics of dextromethorphan O-demethylation were similar in liver microsomes from African green (n = 21) and Crab eater (Macaca fascicularis, n = 7) monkeys (Km = 1.1 +/- 0.07 and 1.7 +/- 0.27 microM; Vmax = 215 +/- 71.7 and 152 +/- 21.1 nmol/mg/h, respectively). These Km values were lower and less variable than those in liver microsomes from 10 human extensive metabolizers (5.3 +/- 2.43 microM). Furthermore, the Vmax of the reaction in human liver microsomes was significantly lower (32 +/- 15.7 nmol/mg/h; P < .001). Inhibitor constants (Ki values) determined in monkey and human liver microsomes were highly correlated (r = 0.97), but two high-affinity inhibitors of the human enzyme (quinidine and lobeline) were approximately 40 fold less potent in monkey livers than in human livers. These data show that the monkey enzyme is functionally homologous, but is not identical to human hepatic cytochrome P450 2D6. Failure to observe poor metabolizer monkeys does not preclude their potential usefulness in evaluating the role of human hepatic cytochrome P450 2D6 activity in drug addiction and neurotoxicity because of the possibility of producing poor metabolizer phenocopies by potent hepatic cytochrome P450 2D6-like enzyme inhibitors in monkeys. PMID- 8355204 TI - Effects of emetine on the specific association of T-2 toxin with mammalian cells. AB - The effects of emetine on the association of T-2 toxin with Chinese hamster ovary cells were examined. T-2 toxin-cell association at both 4 degrees C and 37 degrees C was reduced by up to 90% after preincubation of cells with emetine. Emetine-induced reduction in T-2 toxin-cell association was time-, temperature-, and concentration-dependent. A 4-min preincubation with emetine at physiological temperature was required to develop the maximum inhibitory effect. After brief exposures (< or = 5 min), emetine's inhibitory effects on toxin-cell association were reversible. However, after longer exposure periods to emetine (60 min), toxin-cell association was irreversibly blocked. The addition of emetine to cells prebound with toxin resulted in dissociation at a rate 2 to 3 times slower than a competitive chase with nonlabeled toxin. Emetine did not compete directly for T-2 toxin binding to its receptor on isolated, purified, run-off ribosomes. However, the binding of toxin to purified ribosomes prepared from cells preincubated with emetine was markedly reduced. Scatchard analysis indicated that emetine's inhibitory effects on T-2 toxin-cell association were mediated through mixed allosteric and competitive types of inhibition at specific, intracellular, T-2 toxin ribosomal binding sites. PMID- 8355203 TI - Synergistic effect of nicotinamide and choline administration on extracellular choline levels in the brain. AB - Experimental studies indicate that the availability of free choline is a rate limiting step for acetylcholine synthesis in central cholinergic neurons, especially when the release of acetylcholine is increased. In the present study we applied the microdialysis technique to measure the concentration of extracellular choline in the rat hippocampus. The i.p. injection of 6, 20 and 60 mg/kg of choline chloride led to short-lasting elevations of the basal choline efflux (1.78 pmol/min) by 14, 26 and 131%. N-Methylnicotinamide, a metabolite of nicotinamide, has been reported to inhibit the outward transport of choline from the cerebrospinal fluid to the blood. The s.c. injection of 5 and 10 mmol/kg of nicotinamide caused increases of extracellular choline by 54 and 113%, respectively, and choline levels remained elevated for several hr. Moreover, the administration of 10 mmol/kg of nicotinamide dramatically potentiated the effects of exogenous choline administration on choline availability in the central nervous system. The effects of 6 and 20 mg/kg of choline chloride were increased by a factor of more than 10-fold when determined as area under the curve. Additional experiments demonstrated that neither nicotinamide nor N methylnicotinamide (100 microM) have an influence on the uptake, metabolism or release of choline in the hippocampal slice preparation. It is likely, therefore, that nicotinamide, after metabolic conversion in the brain to N methylnicotinamide, leads to a blockade of choline clearance from the brain. The combined administration of choline and of a choline transport blocker analogous to nicotinamide may be of potential use in central cholinergic dysfunction. PMID- 8355205 TI - Effect of emetine on T-2 toxin-induced inhibition of protein synthesis in mammalian cells. AB - Chinese hamster ovary cells were used to examine the effect of emetine upon the toxicity of T-2 toxin and several related trichothecene inhibitors of polypeptide synthesis. Emetine inhibited protein synthesis and T-2 toxin-cell association in a concentration-dependent manner. The dose-response curves for these two effects were nearly identical. Over a narrow concentration range (0.3-3.0 micrograms/ml), emetine's inhibition of protein synthesis was partially reversible, whereas its inhibition of toxin-cell association was maintained for extended periods. This sustained inhibition of toxin-cell association, resulted in "desensitized" cells with reduced sensitivity to the inhibitory effects of T-2 toxin on protein synthesis. Similar results were obtained when emetine-preincubated cells were challenged with diacetoxyscirpenol, verrucarin A and roridin A. In contrast, there were no measurable effects of emetine upon the response of the cells to the less potent trichothecenes, deoxynivalenol, T-2 tetraol and verrucarol. In addition to emetine, several other inhibitors of polypeptide synthesis were examined for their effects on T-2 toxin-cell association and sensitivity to T-2 toxin. Of these, only cycloheximide inhibited toxin-cell association. Unlike emetine, sustained protection against the effects of T-2 toxin was not observed with cycloheximide. PMID- 8355206 TI - Cerebral catecholamine depletion in mice withdrawn from repeated morphine treatment and development of tolerance to the enhancing effect of morphine on noradrenaline depletion. AB - The effect of repeated morphine administration on the alpha-methyl-rho-tyrosine (alpha M rho T)-induced depletion of catecholamines was investigated in various brain areas of mice withdrawn for 1, 2, 3 and 7 days from 5-day morphine treatment. In addition, to clarify the development of tolerance, the effect of acute morphine administration on alpha M rho T-induced depletion of catecholamines was studied in these selected brain areas of mice withdrawn from repeated morphine treatment. Dopamine depletion was significantly (P < .01) retarded in the striatum and "rest of forebrain + midbrain" of mice withdrawn for 1 day from morphine treatment. Withdrawal from morphine treatment did not alter alpha M rho T-induced noradrenaline depletion in the lower brain stem, rest of forebrain + midbrain or hypothalamus. The 10-mg/kg test dose of morphine significantly enhanced alpha M rho T-induced dopamine depletion in the rest of forebrain + midbrain of control mice withdrawn for 2 days, but did not clearly enhance it in mice withdrawn from morphine. The test dose significantly enhanced noradrenaline depletion in all selected brain areas of control mice withdrawn for 1 to 3 days from saline, but tolerance to the test dose developed in morphine withdrawn mice. These results suggest that dopamine depletion is retarded in the striatum and rest of forebrain + midbrain of mice withdrawn for 1 day from repeated morphine treatment. However, noradrenaline depletion remains unchanged in all selected brain areas of mice withdrawn from morphine, and tolerance develops to the enhancing effect of morphine on the depletion of noradrenaline in mice withdrawn for 1 to 2 days from morphine. PMID- 8355207 TI - Evaluation of the reinforcing and discriminative stimulus effects of cocaine in combination with (+)-AJ76 or clozapine. AB - Because self-administration and discrimination of a drug by animals correlate with its abuse and subjective effects in humans, interventions that modify the reinforcing and discriminative stimulus effects of the drug may be useful in the treatment of its abuse. The present study was designed to evaluate the effects of the putative dopamine autoreceptor antagonist (+)-AJ76 (AJ) or the atypical antipsychotic clozapine (CLZ) on the reinforcing and discriminative stimulus effects of cocaine in monkeys. One group of rhesus monkeys (n = 6) was allowed to self-administer cocaine (0.03 or 0.1 mg/kg/injection i.v. fixed-ratio 10, 2 hr/day). A second group of monkeys (n = 5) was trained to discriminate cocaine (0.2 or 0.4 mg/kg i.m., 10 min presession) from saline in a two lever, food reinforced, drug discrimination paradigm. When behavior was stable, AJ or CLZ was administered i.m., 15 or 30 min presession. Intermediate doses of both compounds (1.0-3.0 mg/kg of AJ; 0.3-1.0 mg/kg of CLZ) increased cocaine self administration, while responding remained evenly distributed over the session. A higher dose of CLZ decreased cocaine self-administration in an apparently nonspecific manner. When combined with saline, partial substitution for cocaine was seen in one of three monkeys with AJ and in none with CLZ. In combination with the training dose of cocaine in the discrimination experiment, both AJ and CLZ decreased drug appropriate responding by at least 50% in two of four monkeys, but had little or no effect in the other monkeys up to doses that completely suppressed lever pressing (6.4 mg/kg of AJ; 3.2 mg/kg of CLZ). Taken together, the present findings suggest that any blockade of the reinforcing and discriminative stimulus effects of cocaine by AJ and CLZ was, at best, partial. Furthermore, the stimulant effects of AJ observed in rats were not prominent in monkeys. PMID- 8355208 TI - Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies. AB - The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity stimulated intense interest in neurotoxicology and in the possible toxic etiology of Parkinson's disease. Better understanding of MPTP neurotoxicity may be achieved by studies using 18F-radiolabeled MPTP analogs and positron emission tomography in nonhuman primates. We synthesized three fluorinated analogs of MPTP: 1-methyl-4-(2-fluorophenyl)-1,2,3,6-tetrahydropyridine (2'-F-MPTP), 1 methyl-4-[2-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CF3-MPTP) and 1-methyl-4-[2-(fluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CH2F-MPTP), and developed a method for preparing the latter in 18F-labeled form. We now studied the suitability of 2'-CH2F-MPTP and its hydrolysis products as substrates for monoamine oxidase (MAO) from mouse and monkey brain preparations, and investigated the neurotoxic effect of 2'-CH2F-MPTP and 2'-F-MPTP on the nigrostriatal dopaminergic system in mice. We found that 2'-CH2F-MPTP is a better substrate for MAO and that both 2'-CH2F-MPTP and 2'-F-MPTP were more potent neurotoxins than MPTP. Like MPTP, 2'-F-MPTP was exclusively oxidized by MAO-B and its toxicity blocked by pargyline or deprenyl but not by clorgyline. In contrast, 2'-CH2F-MPTP was oxidized by both MAO-A and MAO-B, and its toxicity was not blocked by pargyline, clorgyline or deprenyl when given separately, but required clorgyline and deprenyl together. PMID- 8355209 TI - N-acetyl-aspartylglutamate modulation of N-methyl-D-aspartate-stimulated [3H]norepinephrine release from rat hippocampal slices. AB - The release of preloaded radiolabeled norepinephrine ([3H]NE) from slices of rat hippocampus can be stimulated by excitatory amino acids that interact with the N methyl-D-aspartate (NMDA) receptor. The acidic dipeptide N-acetyl-L aspartylglutamate (NAAG) is colocalized with NE in the cell bodies of locus coeruleus (the origin of the noradrenergic projections to the hippocampus) and the hippocampus itself. The function of NAAG in these neurons has not been demonstrated, although evidence exists that it may serve as a neuromodulator in other neuronal pathways. NAAG inhibited the release of [3H]NE stimulated by NMDA and L-glutamate in a concentration-related manner. The maximal inhibition produced by NAAG was about 25% of the control release stimulated by 25 microM NMDA. The effects observed were caused by the intact dipeptide and not the degradation artifacts produced by the enzyme N-acetylated-alpha-linked-acidic dipeptidase because N-acetyl-L-aspartate had no significant effect on the release and L-glutamate was stimulatory. The activity of this enzyme appears to be suppressed under the assay conditions used. Although the addition of glycine did not enhance NMDA-stimulated release, 7-chlorokynurenate and 1-hydroxy-3-amino pyrrolidone-2 decreased the release in a concentration-dependent manner. Furthermore, the attenuation produced by NAAG plus 7-chlorokynurenate or 1 hydroxy-3-aminopyrrolidone-2 was greater than the inhibitory actions of either glycine antagonist alone. Similarly, NAAG produced additional inhibition over that produced by either of two different voltage-dependent calcium channel blockers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355210 TI - Acute effects of cocaine on anterior pituitary hormones in male and female rhesus monkeys. AB - The effects of acute cocaine administration (0.4 or 0.8 mg/kg) on anterior pituitary hormones were studied in four male and six female adult rhesus monkeys during the midluteal phase of the menstrual cycle (days 20-23). Progesterone levels averaged 15.7 +/- 3 and 10.6 +/- 2.8 ng/ml before low and high dose cocaine administration. Integrated plasma samples were collected every 10 min for 40 min before i.v. administration of cocaine, and 11 postcocaine samples were collected over 110 min. Cocaine (0.8 mg/kg) stimulated a significant increase in luteinizing hormone (LH) within 10 to 20 min (P < .01) and LH reached peak levels (59-60% above base line) within 30 min after cocaine administration in both males and females. Plasma cocaine levels averaged 289 +/- 23 and 346 +/- 73 ng/ml at 10 min after i.v. cocaine (0.8 mg/kg) administration in males and females, respectively. Follicle stimulating hormone levels were unchanged in midluteal females. Male testosterone increased by 50% above average base-line levels 50 min after the LH peak (80 min postcocaine). These data are consistent with our previous findings that cocaine increased LH and enhanced luteinizing hormone releasing hormone-stimulated LH in early follicular females. The low dose of cocaine did not change basal levels of LH and follicle stimulating hormone in midluteal females and both LH and testosterone were unaffected in males. Cocaine plasma levels averaged 97.6 +/- 29 and 68.3 +/- 9.1 ng/ml at 10 min after 0.4 mg/kg of cocaine in males and females, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355211 TI - Effect of active sensitization on the bronchopulmonary responses to tachykinins in the guinea pig. Modulation by peptidase inhibitors. AB - The i.v. administration of substance P (SP, 0.25-16 micrograms/kg) or of the selective metabolic stable NK-1 agonist, [Glp6,Pro9]SP-(6-11) (septide, 0.03-0.25 microgram) to atropine-treated guinea pigs or to isolated perfused lungs triggered a dose-dependent bronchoconstriction, which was enhanced in animals actively sensitized to ovalbumin. In vivo, bronchial hyper-responsiveness was restricted to SP and to septide, inasmuch as neurokinin A (0.06-1 microgram/kg)- or capsaicin (0.5-32 micrograms/kg)-induced bronchoconstriction were not modified. In contrast, isolated lungs from sensitized guinea pigs exhibited an increased bronchoconstriction also in response to capsaicin (0.01-10 micrograms), which was inhibited by atropine in the medium. Pretreatment of actively sensitized guinea pigs either with indomethacin plus mepyramine, the lipoxygenase inhibitor BW A4C or with the platelet-activating factor antagonist SR 27417, did not modify bronchial hyper-reactivity to SP. Captopril (5 mg/kg i.v.), but not thiorphan (0.8 mg/kg i.v.), increased the SP-induced bronchoconstriction in actively sensitized animals, whereas both inhibitors were equally effective in nonsensitized guinea pigs. Thiorphan, however, did not modify the in vivo response to septide. Our results demonstrate that guinea pigs sensitized to ovalbumin exhibit bronchial hyperreactivity to SP, but not to neurokinin A, as compared to nonsensitized animals, suggesting a decrease in the neutral endopeptidase activity in the airways brought by the immunization. However, the results obtained by using septide indicate that other mechanisms may be involved in the bronchial hyper-reactivity to SP. PMID- 8355212 TI - Modulation of enantioselective metabolism and inversion of ibuprofen by xenobiotics in isolated rat hepatocytes. AB - R-ibuprofen undergoes chiral inversion by the formation of a coenzyme A (CoA) thioester and subsequent epimerization and hydrolysis. Using isolated rat hepatocytes, the interaction of xenobiotics with the inversion and oxidation pathways of ibuprofen enantiomers was determined from the time course of R- and S ibuprofen and ibuprofenyl-CoA during 4-hr incubations with R- or S-ibuprofen (25 microM). By fitting a first-order model, the rate constants of the formation of ibuprofenyl-CoA (K12), oxidation of R-ibuprofen (K10), hydrolysis of ibuprofenyl CoA (K21) and oxidation of S-ibuprofen (K30) were 1.306, 0.284, 6.858 and 0.496 hr-1, respectively. The fractional inversion of R-ibuprofen was 0.75 and the area under the curve for ibuprofenyl-CoA was 203.8 microM min. Coincubation with 50 microM of the cytochrome P450 inhibitors metyrapone and proadifen resulted in significant reductions of K10 and K30; the fractional inversion of R-ibuprofen increased to 116% and 127% and the area under the curve of ibuprofenyl-CoA to 145% and 144% of controls, respectively. Valproic acid and pivalic acid at 50 microM significantly reduced the K12 and increased the K21; the fractional inversion was unchanged but the area under the curve of ibuprofenyl-CoA was significantly reduced to 57% and 28% of controls, respectively. Valproic acid also significantly reduced K10 and K30. p-nitrobenzoic acid at 50 microM significantly increased K21 and reduced the area under the curve of ibuprofenyl CoA to 44% of control but did not influence the fractional inversion. Selective inhibitors of ibuprofen oxidation were found to enhance significantly hepatocellular exposure to the potentially reactive ibuprofenyl-CoA intermediate. PMID- 8355213 TI - Down-regulation of motilin receptors on rabbit colon myocytes by chronic oral erythromycin. AB - Acutely, erythromycin stimulates colonic smooth muscle contraction via action on motilin receptors, but the effects of chronic erythromycin exposure are unknown. Thus contraction and motilin binding studies were performed on rabbit colonic smooth muscle after 2 weeks of oral erythromycin ethyl succinate (25 mg/kg, twice a day). Isolated colon myocytes from untreated rabbits contracted to erythromycin with an EC50 of 30 +/- 17 pM and peak shortening of 24.1 +/- 0.8% at 10 nM. Motilin evoked similar contractions with an EC50 of 63 +/- 13 pM and peak shortening of 26.8 +/- 0.9% at 10 nM. Myocytes from treated rabbits exhibited reduced contractile responses to erythromycin with an EC50 of 203 +/- 27 pM (P < .002) and decreased peak shortening to 20.1 +/- 2.9% at 100 nM (P < .05). Motilin responses were also blunted [EC50 of 326 +/- 16 pM, peak shortening of 16.2 +/- 1.2% at 1 microM (P < .002)]. [125I]motilin binding to untreated colon smooth muscle homogenates was saturable and specific with a Kd of 0.53 +/- 0.10 nM and a Bmax of 48 +/- 6 fmol/mg protein. Muscle from treated rabbits exhibited no change in motilin receptor affinity (Kd = 0.50 +/- 0.08 nM) but showed a 63% reduction in receptor density (Bmax = 18 +/- 4 fmol/mg protein; P < .03). In conclusion, chronic erythromycin administration results in decreased contractile potency and efficacy of motilin and erythromycin on colonic myocytes, associated with decreased motilin receptor density but no change in receptor affinity. Thus chronic erythromycin exposure leads to tolerance to its colonic smooth muscle motor effects via motilin receptor down-regulation. PMID- 8355214 TI - Droperidol exerts dual effects on repolarization and induces early afterdepolarizations and triggered activity in rabbit Purkinje fibers. AB - This study was designed to clarify discrepancies concerning the effects of droperidol on cardiac repolarization. Myocardial electrical activity was recorded by using microelectrode technique in rabbit Purkinje fibers and guinea pig ventricular muscle. In Purkinje fibers stimulated at 60 pulses/min, low concentrations (0.01-0.3 microM) of droperidol increased in a dose-dependent fashion action potential duration (APD) without altering the other parameters. At 1 and 3 microM, droperidol led to the reversal of the prolonging effect. The highest concentrations used (10 and 30 microM), produced shortening in APD at 50% repolarization concomitantly with a significant decrease in Vmax, action potential amplitude and resting membrane potential. Inexcitability occurred in 4 of 15 preparations exposed to 30 microM. In 8 of 15 Purkinje fibers, the prolonging effect induced by low concentrations was so important that APD exceeded the 1000-msec period of basal stimulation and early afterdepolarizations (EADs) and triggered activity developed. In guinea pig ventricular muscle, these effects were notably less pronounced. Prolongation of action potential showed a reverse use-dependence (i.e., much greater at the lowest stimulation frequencies), whereas Vmax depression was use-dependent. Decreasing extracellular K concentration from 4.0 to 2.7 mM enhanced the incidence of EADs in Purkinje fibers, whereas elevating the K concentration from 2.7 to 5.4 mM abolished them completely and shortened drastically APD. EADs were also eliminated by increasing magnesium concentration from 1 to 5 mM. Addition of isoproterenol favored EADs, whereas these were suppressed at plateau level by exposure to 0.3 microM nifedipine. The results indicate that in rabbit Purkinje fibers, droperidol exerts a dual effect on repolarization, prolongation with low concentrations with development of EADs and subsequent triggered activity. These abnormalities were suppressed at high concentrations concomitantly with a marked depression of other characteristics. These observations suggest multiple ionic channel activities and further studies are required to precise the underlying mechanisms at channel level. PMID- 8355215 TI - Stereoselective verapamil disposition and dynamics in aging during racemic verapamil administration. AB - Stereoselective verapamil disposition and dynamics were evaluated after racemic verapamil administration of single i.v. doses, simulated steady-state intravenous infusions, chronic (1 week) administration of oral immediate-release tablets (120 mg three times daily) and chronic (1 week) administration of oral sustained release tablets (240 mg once daily) to 15 young (mean +/- S.E.M. age 22 +/- 1 year) and 15 older (69 +/- 1 year) healthy male volunteers. After single i.v. doses S-verapamil clearance (young, 102 +/- 6 vs. older, 77 +/- 6 l/hr; P < .01) and R-verapamil clearance (young, 61 +/- 3 vs. older, 45 +/- 3 l/hr; P < .01) were similarly decreased. Electrocardiographic P-R prolongation using S-verapamil concentrations and an Emax model (young Emax, 69 +/- 8 vs. older, 42 +/- 6 msec; P < .05: young EC50, 15 +/- 1 vs. older, 23 +/- 3 ng/ml; P < .05) was greater in the young. Simulated steady-state i.v. S-verapamil clearance (young, 76 +/- 3 vs. older, 49 +/- 2 l/hr; P < .01) and R-verapamil clearance (young, 47 +/- 2 vs. older, 28 +/- 1 l/hr; P < .01) were similarly less in older subjects and this was unrelated to infusion rate. Qualitatively similar findings were observed during chronic oral (immediate release) treatment and chronic oral (sustained release) treatment. Plasma protein binding of S-verapamil was less in both groups (young, 8.5 +/- 0.4 and older, 8.0 +/- 0.5% unbound) than that of R-verapamil (young, 5.4 +/- 0.2 and older, 5.1 +/- 0.3% unbound) and not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355216 TI - DOI and alpha-methylserotonin: comparative vascular and nonvascular smooth muscle effects and central 5-hydroxytryptamine2 receptor affinities. AB - Both alpha-methylserotonin and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) are agonists at 5-hydroxytryptamine2 (5-HT2) receptors. The present study compared these agonists for their binding affinities at the high- and low affinity states of the 5-HT2 receptor and for their contractile activities in certain smooth muscle preparations. Both agonists contracted the rat aorta and rat jugular vein, tissues possessing 5-HT2 receptors, and contraction was blocked by ketanserin. However, alpha-methylserotonin produced greater maximal response (80-90% maximum response to serotonin) than DOI. In the rat jugular vein, the calculated dissociation constant of DOI (-log Kb = 7.7) corresponded well with its affinity for [3H]ketanserin- (pKi = 7.5) but not [125I]DOI- (pKi = 8.6) radiolabeled sites. This might suggest that binding to the agonist low-affinity state of the 5-HT2 receptor is more relevant to vascular agonist activity. alpha Methylserotonin was slightly more potent than serotonin in contracting the rat aorta but not the jugular vein, whereas DOI was more potent in the jugular vein than in the aorta. In the jugular vein but not the aorta, the relative potency of these agents corresponded well with their relative affinities for either the [3H]ketanserin- or the [125I]DOI-labeled 5-HT2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355217 TI - Cytochrome P450 2B isoenzymes are responsible for the pulmonary bioactivation and toxicity of butylated hydroxytoluene, O,O,S-trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl. AB - O,O,S-Trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl damage the type I pneumocytes of the alveolar epithelium in rats. Butylated hydroxytoluene causes similar damage in mice. The toxicity of these compounds is dependent on their bioactivation by the cytochrome P-450 (CYP) system. A range of compounds, that modifies the activity of specific CYP isoenzymes, has been used to establish those particular isoenzymes involved in bioactivation. Pulmonary toxicity was assessed by measurement of lung weight and changes in the activity of gamma-glutamyltranspeptidase and alkaline phosphatase in bronchoalveolar lavage fluid. O,O,S-Trimethylphosphorodithioate, bromophos, p-xylene and 2,4 dichloro-(6-phenyl-phenoxy)ethylamine all inhibited the dealkylation of pentoxyresorufin, an indicator of CYP2B1 activity, and also prevented pulmonary toxicity. There was a significant negative correlation between the level of pulmonary pentoxyresorufin dealkylation after pretreatment with O,O,S trimethylphosphorodithioate and the severity of lung injury. This pretreatment also reduced the toxicity of butylated hydroxytoluene by a factor of 20 and methylcyclopentadienyl manganese tricarbonyl by a factor of 10. Modification of the activity of CYP1A1, CYP2E1 and CYP4B1 did not alter the toxicity of these compounds. These results indicate that pulmonary CYP2B1 is responsible for the bioactivation and toxicity of O,O,S-trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl in rats and the orthologous 2B isoenzyme in mice activates butylated hydroxytoluene. PMID- 8355218 TI - Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. AB - (R)- and (S)-fluoxetine were found to be competitive inhibitors of P450 2D6 mediated bufuralol 1'-hydroxylation in vitro, yielding Ki values of 1.38 +/- 0.48 and 0.22 +/- 0.11 microM, respectively. Their N-demethylated metabolites were also found to be potent inhibitors (Ki, (R)-norfluoxetine, 1.48 +/- 0.27 microM; (S)-norfluoxetine, 0.31 +/- 0.04 microM). The microsomal (R)- and (S)-fluoxetine N-demethylase activities for 14 human liver samples were on average 29.6 +/- 13.5 and 19.4 +/- 11.8 pmol of product/min/mg of protein, respectively. The individual rates of N-demethylation correlated with microsomal immunodetectable P450 2D6 levels; (R)-fluoxetine, r = 0.64, P < .05; (S)-fluoxetine, r = 0.63, P < .05. However, this correlation was significantly weaker than the excellent correlation obtained for P450 2D6-marker bufuralol 1'-hydroxylase activity and P450 2D6 levels (r = 0.92, P < or = .01). Quinidine, a potent inhibitor of P450 2D6, inhibited the demethylation of each enantiomer by only approximately 20% at a concentration 300 times greater than the Ki determined for the quinidine inhibition of bufuralol 1'-hydroxylase. Furthermore, antiserum recognizing P450 2D6 inhibited 82% of microsomal bufuralol 1'-hydroxylase activity but only 27% of the (R)-fluoxetine N-demethylase activity in the same human liver sample. In summary, these data indicate that the enantiomers of fluoxetine and norfluoxetine are potent inhibitors of P450 2D6 and that P450 forms other than P450 2D6 appear to be responsible for the majority of microsomal fluoxetine N-demethylation. PMID- 8355219 TI - Interaction of thiazide and loop diuretics with the basolateral para aminohippurate transport system in isolated S2 segments of rabbit kidney proximal tubules. AB - The effect of thiazide and loop diuretics on the tubular uptake of [3H]para aminohippurate ([3H]PAH), a marker of the organic anion transport system, was tested in vitro on single S2 segments of the proximal tubule of rabbit kidneys. Because the tubules were not perfused, and hence were collapsed, the tubular [3H] PAH uptake reflects [3H]PAH transport across the contraluminal membrane. The diuretics were added to the bath solution in at least six different concentrations. The concentration of [3H]PAH in the bath solution amounted to 1.3 mumol/l, and was 12 times lower than the PAH concentration (16 mumol/l) at half maximum PAH uptake. The results show that all of the nine diuretics tested inhibited [3H]PAH uptake. The IC50 values of the individual drugs ranged from 3 to 400 mumol/l. In general, thiazide diuretics had a lower affinity to the PAH transporter than loop diuretics. This probably results from differences in the pKa values which range from 3.6 to 4.1 for the loop diuretics and from 9.2 to 10 for the thiazide diuretics. Furthermore, there was a highly significant dependence of affinity on the hydrophobic properties of the diuretics. At concentrations 10- to 100-fold lower than the IC50 values all diuretics stimulated [3H]PAH uptake which may indicate a positive cooperative interaction of these drugs with the PAH transporter. Within the group of loop diuretics the order of the affinity to the PAH transporter and to the Na, 2 Cl, K cotransporter in the thick ascending limb of Henle's loop was identical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355220 TI - Proceedings of the scientific meetings of The Physiological Society. June, July, and September 1992. Abstracts. PMID- 8355221 TI - Proceedings of the scientific meetings of The Physiological Society. December 1992, January and April 1993. Abstracts. PMID- 8355222 TI - Pathology of intraoral sebaceous glands. AB - Large clinical studies have shown that intraoral sebaceous glands are present in 70 to 95% of the population. In many individuals these small white to yellow macules and papules are so numerous that they dominate the buccal mucosa. Despite their prevalence, pathological changes of these glands are considered uncommon. This paper reviews the pathologic spectrum of intraoral sebaceous glands including Demodex infestation, cystic lesions, sebaceous hyperplasia and neoplastic lesions. New data is presented on the true sebaceous cyst and the second reported case of intraoral steatocystoma simplex is documented. PMID- 8355223 TI - Tissue markers of potentially malignant human oral epithelial lesions. AB - Tissue markers of potential malignancy have been sought for many years. Cell surface markers, particularly blood group and histocompatibility antigens, have shown great promise and several squamous carcinoma antigens have been identified- but not fully studied in potentially malignant lesions. Growth factors and receptors also need further study. Cytoplasmic markers of potential malignancy have been examined and, of these, keratins, filaggrin, and some carcinoma antigens show most promise. Nuclear analyses have promise but are time-consuming and expensive. Image cytometric analyses appear to be sensitive and predictive: oncogene and tumour suppressor analyses remain to be fully evaluated. New investigative techniques at the cellular and molecular level show increasing promise at defining potentially malignant oral epithelial lesions but more prospective studies are required. PMID- 8355224 TI - Comparing flow cytometric analysis and nucleolar organizer region enumeration in archival oral premalignant lesions. AB - Flow cytometric analysis (FCA) and silver colloidal nucleolar organizer region associated protein staining (AgNOR) have been used individually in assessing the histopathologic nature of various human tumors. However, few researchers have investigated the relationship between the two techniques in a single series. In a retrospective study, we examined 36 premalignant lesions of the oral cavity by FCA and AgNOR on formalin-fixed, paraffin-embedded tissue submitted to the University of Tennessee, Memphis, oral pathology laboratory. Three categories of epithelial dysplasia were represented (9 mild, 9 moderate, 6 severe), as well as four epithelial hyperplasias without dysplasia, three squamous cell carcinomas, and five fibrous nodules as controls. Parameters recorded for each case included age, race, gender, site, light microscopic diagnosis (LMD), DNA index (DI), total proliferative index (TPI), S-phase (S), range of nucleolar organizer regions (RNOR), and mean number of nucleolar organizer regions (MNOR). The average maximum nucleolar organizer region count (AMXNOR) for each LMD category was also calculated. The objective of the study was to determine if FCA or AgNOR aided in the subjective LMD of oral premalignant lesions and if the parameters recorded for the specimens exhibited any positive correlation. The FCA results indicated an abnormal DI in 6 of the 24 dysplastic lesions. A positive partial correlation was seen between DI and MNOR (r = 0.434; P < 0.012) and TPI and S (r = 0.774; P < 0.0001), holding gender and race constant. Additionally, the AMXNOR exhibited a slight tendency to increase for each increasing grade of dysplasia but this could not be confirmed statistically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355225 TI - Cartilage in the walls of odontogenic keratocysts. AB - Only one histologically documented case of cartilage in the wall of an odontogenic keratocyst has been reported in the English language literature. Four new cases are presented with the clinical, radiographic and histopathologic features described. To our knowledge this finding has not been reported in association with any other type of odontogenic cyst. PMID- 8355226 TI - The terminally ill patient on an acute psychiatric unit. A case study. AB - 1. As mental health professionals, we frequently fail to realize that we are subject to the same emotions and coping mechanisms as the lay community. 2. At times it seems safer to focus on a patient's medical condition than to deal with difficult, unresolved psychological issues. 3. By using existing resources within our institution, our interdisciplinary team faced many of their unresolved issues about death, such as countertransference, and were able to then help our patient through his final stage of life. PMID- 8355227 TI - Coming out. My experience as a mental patient. AB - 1. There is still a strong stigma attached to mental illness, and surprisingly many psychiatric nurses reinforce that stigma. Although some professionals may go into therapy to improve self-esteem and become better professionals, they may run the risk of destroying their career. 2. The experience as a patient in a mental health facility can result in nightmares and flashbacks, and damage due to restraints. Because "coming out" can destroy one's career, the safest place for a nurse with a history of hospitalization or substance abuse may be "in the closet." 3. If the stigma of mental illness is going to be changed, then it must start with the changing of the attitudes and perceptions of mental health professionals. PMID- 8355228 TI - Social organization of length of stay of psychiatric patients. AB - 1. Length of stay (LOS) is the major factor determining the use of resources in hospitals and is the primary component in reducing hospital costs. However, relatively little is known about the anatomy of the hospital stay. 2. The stage model of treatment is used to examine the LOS of psychiatric patients. The model assumes the patient is admitted to the hospital, undergoes testing or observation to verify a diagnosis or establish a new diagnosis, and then proceeds to therapy, recovery, and discharge. 3. In practice, the treatment process does not follow a stage model, but is much more complicated. Various kinds of information are revealed throughout the course of hospitalization and treatment continues as events unfold. Diagnosis, therapy, and recovery occur in a dialectical process constantly being reconstructed as it is informed by interpretations of everyday events. PMID- 8355229 TI - Depression in the elderly. AB - 1. Depression in the elderly is a major health concern that can be life threatening if not recognized and treated. An untreated depression may result in needless suffering, institutionalization, and suicide. Lack of treatment may occur because the signs and symptoms of depression in the elderly are different from those in the young, and because depressive symptoms may be viewed by the older person, the family, and the physician as a normal part of aging. 2. Depression can occur secondarily to physical illness. Because physical illnesses occur frequently in the older population, the combination of physical illness and depression is common. 3. Through noninvasive procedures, such as positron emission tomography (PET), a greater understanding of depression will be achieved that will result in development of more specific and effective treatment. Accurate and early diagnosis and adequate treatment favor a good prognosis. PMID- 8355231 TI - Just between us. PMID- 8355230 TI - Expanding uses of anticonvulsants in the treatment of bipolar disorder. PMID- 8355232 TI - Networking: a vital tool. PMID- 8355233 TI - Use of the brief psychiatric rating scale by nurses. AB - 1. Nurses are intimately involved in the assessment of patients in inpatient clinical settings and in community settings--and nurses have a role to play in the systematic rating of severe psychopathology. 2. The Brief Psychiatric Rating Scale (BPRS) provides a means of assessing mental health status from an interview using 16 rating concepts. Analysis of BPRS rating profiles obtained from a variety of patients and settings have consistently revealed four syndromes: withdrawal-retardation, anxious depression, hostile-suspiciousness, and thinking disturbance. 3. Once properly trained regarding the BPRS, nurses can use the scale effectively in the assessment and ongoing monitoring of patient conditions. The scale is an added tool for nurses to use in monitoring the effectiveness and outcome of both medical and nursing interventions. PMID- 8355234 TI - Community care. PMID- 8355235 TI - Prevention and management of panic in personnel facing a chemical threat--lessons from the Gulf War. AB - During the Gulf War a number of subjects presented with panic, hyperventilation, and inability to wear respirators when chemical alarms were sounded, despite a perceived real chemical threat. Twenty-five such sufferers were seen at the Psychiatric Department of 33 General (Surgical) Hospital. This paper considers the aetiology of such responses, describes a mode of treatment which can be used in the threat situation, and considers issues of future training. PMID- 8355236 TI - Acetic acid used for the elimination of Pseudomonas aeruginosa from burn and soft tissue wounds. AB - Acetic acid was used topically at concentrations of between 0.5% and 5% to eliminate Pseudomonas aeruginosa from the burn wounds or soft tissue wounds of 16 patients. In-vitro studies indicated the susceptibility of P. aeruginosa to acetic acid; all strains exhibited a minimum inhibitory concentration of 2 per cent. P. aeruginosa was eliminated from the wounds of 14 of the 16 patients within two weeks of treatment. Acetic acid was shown to be an inexpensive and efficient agent for the elimination of P. aeruginosa from burn and soft tissue wounds. PMID- 8355237 TI - The RAF Community Psychiatry Service in Cyprus. PMID- 8355238 TI - Brief therapy in a battleshock recovery unit: three case studies. AB - Combat stress reactions may present in many forms. This study presents three cases from the Gulf War which illustrate the diversity of presentation and demonstrate the ways in which the principles of the management of Combat Stress Reactions--Proximity, Immediacy and Expectancy--can be combined with specific individual therapies. PMID- 8355239 TI - Necrotising fasciitis of the leg as a complication of ischiorectal abscess. AB - This case report describes the rare complication of necrotising fasciitis of the right thigh and calf after drainage of an ischiorectal abscess. The important early symptoms and signs of this life threatening infection, and the need for urgent treatment with aggressive surgical debridement and broad spectrum antibiotics, are emphasised in order to facilitate early recognition and prompt initiation of the appropriate therapy in future cases. PMID- 8355240 TI - A case of 'epilepsy' successfully treated by cardiac pacing. PMID- 8355241 TI - Herpes simplex virus encephalitis. PMID- 8355242 TI - Penetrating chest trauma. PMID- 8355244 TI - Sports medicine. PMID- 8355243 TI - The blue epidemic cholera--some aspects of treatment in the mid 19th century. AB - Cholera was first recorded in the Indian sub-continent in 1817 from where pandemics reached Europe via trade and pilgrim routes. Notwithstanding the numerous therapeutic methods prescribed, the virulence of cholera remained unabated. This article describes some of the proposed treatment regimes in relation to the assumed pathophysiology. PMID- 8355245 TI - Activated ketone based inhibitors of human renin. AB - Application of the concept of activated ketones to the design of novel and potent transition-state analog inhibitors of the aspartyl protease renin is described. Three different classes of peptidic activated ketones were synthesized: 1,1,1 trifluoromethyl ketones, alpha-keto esters, and alpha-diketones. The corresponding alcohols were also evaluated as renin inhibitors in each series. While the trifluoromethyl alcohol 12 (I50 = 4000 nM) was equipotent to the simple methyl alcohol 7 (I50 = 3200 nM), the structurally similar alpha-hydroxy esters (32 and 30, I50's = 5.3 and 4.7 nM, respectively) and alpha-hydroxy ketones (41 and 42, I50 = 23 and 15 nM, respectively) were 150-300-fold more active. The hydrating capability of the activated ketone functionality was important for intrinsic potency in the case of trifluoromethyl ketones, as illustrated by the significantly better activity of trifluoromethyl ketone 13 (I50 = 250 nM) compared to its alcohol analog 12 (I50 = 4000 nM). It was however unimportant for the alpha-keto ester (20 and 31, I50 = 15 and 4.1 nM, respectively) and alpha diketone (43 and 44, I50 = 52 and 28 nM, respectively) based inhibitors, since their activity was essentially similar to that of the corresponding alcohols. These results collectively suggest that, whereas the trifluoromethyl ketones derive their renin inhibitory potency primarily from their ability to become hydrated, this is not a critical feature for the activity of alpha-dicarbonyl based inhibitors. The alpha-keto ester and alpha-diketone based renin inhibitors benefit predominantly from the hydrophobic and/or H-bonding type binding interactions of the neighboring ester or acyl group itself, rather than the ability of this group to deactivate the adjacent ketone group and thereby make it susceptible to hydration. PMID- 8355246 TI - Synthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: orally active iron chelators with clinical potential. AB - The synthesis of a range of novel bidentate ligands containing the chelating moiety 3-hydroxy-4(1H)-pyridinone is described. The pKa values of the ligands and the stability constants of their iron(III) complexes have been determined. The crystal structures of one of the ligands and one of the iron(III) complexes are presented. The distribution coefficients of the ligands are reported and are related to the ability of the ligands to remove iron from hepatocytes. The influence of 3-hydroxy-4(1H)-pyridinones on oxidative damage to cells is described. In contrast to the iron chelator in current therapeutic use, desferrioxamine-B, many of the bidentate ligands described in this study are orally active in iron-overloaded mice. PMID- 8355247 TI - Tyrosine kinase inhibitors. 1. Structure-activity relationships for inhibition of epidermal growth factor receptor tyrosine kinase activity by 2,3-dihydro-2-thioxo 1H-indole-3-alkanoic acids and 2,2'-dithiobis(1H-indole-3-alkanoic acids). AB - A series of 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids, and their methyl esters were prepared, the majority by oxidation of 1H-indole-3-alkanoic acids (DMSO/HCl), followed by thiation of the corresponding 2,3-dihydro-2-oxo-1H-indole 3-alkanoic acid esters. The monomeric thiones undergo facile and reversible oxidation to the corresponding 2,2'-dithiobis(1H-indole-3-alkanoic acids). The compounds were evaluated for their abilities to inhibit the tyrosine kinase activity of the epidermal growth factor receptor using a native complex contained in plasma membrane vesicles shed from cultured A431 cells, and to inhibit the growth of Swiss 3T3 mouse fibroblast in culture. Enzyme inhibitory activity is dependent on the length of the side chain, with propanoic acid derivatives showing the highest activity. The acids are generally significantly more potent than the corresponding esters, and the disulfides more active than the corresponding monomers. An ability to undergo the thione-thiol tautomerism necessary for dimerization is essential, with 3,3-disubstituted compounds being inactive. Overall, the data suggest that the disulfide is the more active form, with much of the activity of the monomeric thiones being due to varying degrees of conversion to the disulfide during the assay. In the growth inhibition assay, the methyl esters are more potent than their corresponding carboxylic acids, and the dimers are generally more potent than the monomers. The data show these compounds to be a novel and potent class of inhibitors of epidermal growth factor receptor tyrosine kinase activity. PMID- 8355248 TI - A pharmacological, crystallographic, and quantum chemical study of new inotropic agents. AB - The cardiac activity of a series of milrinone analogues, 2-substituted 3-acyl-1,6 dihydro-6-oxo-5-pyridinecarbonitriles, 1,6,3,2,11,12-hexahydro-6,3-dioxo-5 quinolinecarbonitriles, the correlated carboxylic acids, 2-substituted 3-acyl 6(1H)-pyridones, and 7,8-dihydro-2,5(1H,6H)-quinolinediones, was evaluated in spontaneously beating and in electrically driven atria from reserpine-treated guinea pigs. Their effects were compared with those induced by amrinone and milrinone in both the atria preparations. Compounds SF28 (3-acetyl-1,6-dihydro-2 methyl-6-oxo-5-pyridinecarbonitrile) and SF40 (7,8-dihydro-7-methyl-2,5(1H,6H) quinolinedione) were the most effective positive inotropic agents. An inhibition of the negative influence exerted by endogenous adenosine on heart preparations seems to be involved in their contractile activity. SF38 (3-benzoyl-2-phenyl 6(1H)-pyridinone), on the contrary, reduced the contractile force and the frequency rate of guinea pig atria with a mechanism not related to an activation of cholinergic or purinergic inhibitory receptors on the heart. X-ray analysis carried out on the three model compounds, SF28, SF40 (positive inotropic agents), and SF38 (negative inotropic agent), and molecular modeling evidenced that the change from phenyl (SF38) to methyl (SF28) or the introduction of a side cyclic aliphatic chain (SF40) results in a variation of conformational preference and topography which may address the different molecules toward distinct receptor pockets according to the resulting inotropic effect. PMID- 8355249 TI - Antihyperglycemic activity of novel naphthalenyl 3H-1,2,3,5-oxathiadiazole 2 oxides. AB - A series of naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non insulin dependent) diabetes mellitus. Substitution at the 1-, 5-, or 8-positions of the naphthalene ring with a halogen was found to be beneficial to antihyperglycemic activity. 4-[(5-Chloronaphthalen-2-yl)methyl]-3H-1,2,3,5 oxathiadiazole++ + 2-oxide (45), one of the most potent compounds in this series, was selected for further pharmacological evaluation. PMID- 8355250 TI - Mono- and bis(aminomethyl)phenylacetic acid esters as short-acting antiarrhythmic agents. 2. AB - The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrrolidinomethyl)-4-hydroxyphenylacetic acid series, the 1,4-benzodioxanyl-2 methyl(3q) and the thienyl-2-methyl(31) esters were evaluated in vivo for antiarrhythmic efficacy. In addition, a number of monoappended phenylacetic esters of 3q with or without the 4-hydroxy group were also prepared for evaluation of antiarrhythmic, lipophilic, and metabolic properties. Of these compounds, 3q possessed the most desirable pharmacological and pharmacokinetic profile. PMID- 8355251 TI - Synthesis and binding properties of MK-801 isothiocyanates; (+)-3-isothiocyanato 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten- 5,10-imine hydrochloride: a new, potent and selective electrophilic affinity ligand for the NMDA receptor coupled phencyclidine binding site. AB - Three new site-directed irreversible (wash-resistant) ligands for the high affinity phencyclidine (PCP) binding site associated with the N-methyl-D aspartate (NMDA) receptor were synthesized and their binding characteristics were studied. (+)-3- And (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H dibenzo[a,d]cycl ohepten-5,10 - imine hydrochloride ((+)-8a,b.HCl) were prepared in four steps from the corresponding nitro derivatives (+)-4a,b, which were obtained by nitration of (+)-3 (MK-801). In the same way the optical antipode (-) 8a.HCl was synthesized from (-)-3. At a concentration of 100 nM, the 3 isothiocyanate derivative (+)-8a irreversibly labeled approximately 50% of the (+)-[3H]-3 binding sites, compared to 20 microM needed for its optical antipode ( )-8a and the 2-isothiocyanate (+)-8b. The apparent Ki values for reversible inhibition of (+)-[3H]-3 binding by (+)- and (-)-8a and (+)-8b were 37,838, and 843 nM, respectively. In contrast, metaphit (1b) and etoxadrol m-isothiocyanate (2b), two previously reported irreversible ligands for the PCP binding site, label about 50% of the (+)-[3H]-3 binding sites at 100 microM and 250 nM, respectively, with apparent Ki values for reversible inhibition of 535 and 94 nM. Compound (+)-8a is also a selective affinity ligand, displaying little or no irreversible in vitro affinity at 100 microM for opioid, benzodiazepine, muscarinic, and dopamine receptors. At a 25 microM concentration, (+)-8a caused an irreversible 52% reduction of binding to sigma 1-receptors. Compound (+)-8a is the most potent known electrophilic affinity label for the PCP binding site. Its potency and selectivity should enable it to be a valuable tool for the elucidation of the structure and function of the NMDA receptor-associated PCP binding site in the mammalian central nervous system. PMID- 8355252 TI - Adenosine A1 antagonists. 3. Structure-activity relationships on amelioration against scopolamine- or N6-((R)-phenylisopropyl)adenosine-induced cognitive disturbance. AB - The effects of a variety of adenosine A1 and A2 antagonists on N6-((R) phenylisopropyl)adenosine (R-PIA)- and scopolamine-induced amnesias were investigated in rodents in order to clarify the role of adenosine receptors in learning and memory. Some of the selective adenosine A1 antagonists exhibited antiamnesic activities at several doses where they did not induce an increase of spontaneous locomotion. These results suggest that the blockade of A1 receptors is more important than that of A2 receptors in learning and memory. Detailed studies of structure-activity relationships of adenosine A1 antagonists in two amnesia models demonstrated that there were three types of adenosine A1 antagonists: (A) Compounds 3-5 (8-substituted 1,3-dipropylxanthines) ameliorated the shortened latency in both models. (B) Compounds 7-11 (8-substituted 1,3 dialkylxanthines) and 19-21 (imidazo[2,1-i]purin-5(4H)-one derivatives) ameliorated the shortened latency in the (R)-PIA-induced amnesia model but not in the scopolamine-induced amnesia model. (C) Compounds 14-16 ameliorated the shortened latency in the scopolamine model but not in the (R)-PIA model. Aminophenethyl-substituted compounds C did not exhibit adenosine A1 antagonism in vivo presumably due to rapid metabolism. The dramatic change in the activities of A and B could not be explained by their simple pharmacokinetic differences because both types of compounds showed clear blockade of central adenosine A1 receptors in the (R)-PIA model. 8-(3-Dicyclopropylmethyl)-1,3-dipropylxanthine (5) (KF15372) was chosen for further studies and is currently under preclinical development as a cognition enhancer. PMID- 8355254 TI - Synthesis and antimalarial activity of some 9-substituted artemisinin derivatives. AB - Several 9-substituted derivatives of the antimalarial drug artemisinin have been prepared by functionalizing the double bond of artemisitene and related compounds. Stereochemical assignments for these compounds were made using a combination of NMR experiments, an X-ray diffraction study of one compound, and chemical correlations of several other compounds with this one compound of unambiguous structure and with its epimer. The compounds synthesized show a wide variation in in vitro antimalarial activity. PMID- 8355253 TI - Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist. AB - DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5-HT1C/2 serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT1C- or 5-HT2 mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT1C- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT1A serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT1C sites and (b) it has been used as a "5-HT2-selective" antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure-affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4 fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]de can-4-on e (26), was shown to bind at 5-HT2 sites with high affinity (Ki = 2 nM) and > 2,000-fold selectivity versus 5-HT1C sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT1C-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist. PMID- 8355255 TI - Triazolinones as nonpeptide angiotensin II antagonists. 1. Synthesis and evaluation of potent 2,4,5-trisubstituted triazolinones. AB - A series of 2,4-dihydro-2,4,5-trisubstituted-3H-1,2,4-triazol-3-ones was prepared via several synthetic routes and evaluated as AII receptor antagonists in vitro and in vivo. The preferred compounds contained a [2'-(5-tetrazolyl)biphenyl-4 yl]methyl side chain at N4 and an n-butyl group at C5. A number of these bearing an alkyl or aralkyl substituent at N2 showed in vitro potency in the nanomolar range (rabbit aorta membrane receptor), and several of these, e.g., the 2,2 dimethyl-1-propyl analogue (54, IC50 = 2.1 nM), effectively blocked the AII pressor response in conscious rats with significant duration (2.5 h at 1 mg/kg orally for 54). Among analogues possessing aryl substituents at N2, ortho substitution on the phenyl moiety resulted in several derivatives with in vitro potency in the low nanomolar range. One of these, featuring a 2 (trifluoromethyl)phenyl substituent at N2 (25, IC50 = 1.2 nM), was effective at 1 mg/kg orally in the rat model, with a duration of > 6 h. Implications for hydrophobic and hydrogen-bonding interactions with the AT1 receptor are discussed. PMID- 8355256 TI - Peptidomimetic HIV protease inhibitors: phosphate prodrugs with improved biological activities. PMID- 8355257 TI - Nitrobenzyl mustard quaternary salts: a new class of hypoxia-selective cytotoxins showing very high in vitro selectivity. PMID- 8355258 TI - Ethyl substitution at the 7 position extends the half-life of 10 hydroxycamptothecin in the presence of human serum albumin. PMID- 8355259 TI - Effects of carbon tetrachloride, menadione, and paraquat on the urinary excretion of malondialdehyde, formaldehyde, acetaldehyde, and acetone in rats. AB - Excretions of the lipid peroxidation products, formaldehyde (FA), acetaldehyde (ACT), malondialdehyde (MDA), and acetone (ACON), were simultaneously identified and quantitated in the urine of female Sprague-Dawley rats by gas chromatography mass spectroscopy (GC-MS) and high pressure liquid chromatography (HPLC) following the acute administration of carbon tetrachloride, a model alkylating agent that does not induce glutathione depletion, and the redox cycling compounds paraquat and menadione. All three xenobiotics are well-known inducers of oxidative stress. Oxidative stress was induced by oral administration of single doses of 2.5 mL of carbon tetrachloride/kg, 60 mg menadione/kg, and 75 mg paraquat/kg. These doses are approximately 50% of the LD50's for the three xenobiotics. Urinary excretion of FA, ACT, MDA, and ACON increased relative to control animals following treatment with all xenobiotics. Over the 48 hours of the study, the greatest increases in the excretion of MDA, FA, ACT, and ACON occurred after paraquat administration, with increases of approximately 2.7-, 2.6 , 4.3-, and 11.0-fold, respectively. This technique may have wide-spread applicability as an effective biomarker for investigating altered lipid metabolism in disease states and exposure to environmental pollutants/xenobiotics. PMID- 8355260 TI - Immobilized rhodanese: some aspects of anion inhibition kinetics and modulation by cations. AB - The rat liver rhodanese (thiosulphate: cyanide sulfurtransferase EC 2.6.1.1) has been immobilized on polyacrylamide gels. The immobilized enzyme had a pH optimum of 7.4 and Km values of 3.25 mM and 1.12 mM for S2O3(2-) and KCN, respectively. The enzyme was competitively inhibited by NaNO2 and CH3COONa and noncompetitively by amyl-nitrite. A modulation of activity was observed in the presence of Ca2+, Zn2+, and Cu2+. The results are discussed in line with the detoxicating function of liver rhodanese. PMID- 8355261 TI - Isolation and characterization of mitochondrial acyl-CoA: glycine N acyltransferases from kidney. AB - When bovine kidney mitochondria were assayed in the presence of Triton X-100, they were found to contain glycine N-acyltransferase activity toward the CoA adducts of benzoate, butyrate, isovalerate, naphthylacetate, phenylacetate, and salicylate. Heptanoyl-CoA activity was masked by high acyl-CoA hydrolase activity. All activities found in detergent-lysed mitochondria, and also that toward heptanoyl-CoA, could be released in soluble form by repeated cycles of freeze-thawing. Activity in the particle-free lysate decreased in the order: phenylacetyl-CoA > benzoyl-CoA > salicylyl-CoA > butyryl-CoA > naphthylacetyl-CoA > heptanoyl-CoA > isovaleryl-CoA. This is quite different from liver, where the activity toward the arylacetic acids is much lower and the other activities are higher. This reflects a major difference in the relative expression of the aralkyl and arylacetyl transferases between liver and kidney. The phenylacetyl CoA and naphthylacetyl-CoA activity purified with a single protein which is termed the arylacetyl transferase. This enzyme was similar to the hepatic arylacetyl transferase in terms of its sensitivity to sulfhydryl reagents, response to cations, and molecular weight (33,500). Activity toward benzoyl-CoA also purified as a single form which was similar to the hepatic form in its molecular weight (34,000), response to cations, and kinetic properties. Conditions leading to the inhibition of this kidney form and also the hepatic form by p-mercuribenzoate are described. PMID- 8355262 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters pancreatic membrane tyrosine phosphorylation following acute treatment. AB - To understand the basic mechanisms of TCDD's action to cause hypoinsulinemia in several experimental animals, we have studied TCDD-induced changes in various protein kinase activities in membrane preparations of guinea pig pancreas. For this purpose, young male guinea pigs were treated through a single intraperitoneal injection with 1 or 3 micrograms/kg of TCDD in vivo, and, after given time periods, pancreas samples were obtained and membranes were isolated through homogenization and centrifugation procedures. Several sets of incubation conditions were selected for protein kinase activity assay, each favoring a specific type of protein kinase. It was found that overall protein phosphorylation activities were higher in the preparation from TCDD-treated animals as compared to those found in pair-fed controls and that this trend was more pronounced when the assay medium contained Mn2+ in place of Mg2+ and EGTA. These are the conditions that are known to favor protein tyrosine kinases. Other types of protein kinases from the treated animals did not show any significant differences from the pair-fed control animals, though that of protein kinase C in the treated preparation showed a modest increase. To establish that the type of protein kinases stimulated by TCDD are protein tyrosine kinases, we have carried out phosphoamino acid analyses, KOH digestion, and western blot analyses using an antibody to phosphotyrosine. All the results were consistent in supporting the idea that TCDD causes a rise in protein-tyrosine kinases in pancreas at early stages of poisoning. PMID- 8355263 TI - The effect of the cytochrome P-450 system inducers on the development of Drosophila melanogaster. AB - D. melanogaster development was markedly retarded and its survival decreased by larvae treatment with compounds being strong inducers of the cytochrome P-450 2B in mammals--phenobarbital (PB*), perfluorodecaline (PFD), transtilbene oxide (TSO), and triphenyldioxane (TPD). At the same time, the weak inducer hexobarbital or the selective cytochrome P-450 inducer in mice but not in rats 1,4-bis[2-(dichloropyridyl-oxy)]-benzene (DPB) did not affect the larvae development. The cytochrome P-450 1A1 inducers benzo(a)anthracene (BA) and beta naphtoflavone (BNF) were also not effective. The toxicity of phenobarbital was shown to be decreased by the cytochrome P-450 inhibitor piperonyl butoxide by adding 20-hydroxyecdysone or by treatment with aminophylline--the indirect enhancer of ecdysone production in the larval prothoracic gland. The hypothesis of the moulting hormone degradation as the cause of elevated larvae mortality resulting from the induced high mixed function oxidase activity has been discussed. PMID- 8355264 TI - Crystallization of barley (1-3,1-4)-beta-glucanase, isoenzyme II. AB - The (1-3,1-4)-beta-glucanase from barley (Hordeum vulgare, cv Alexis) degrades mixed linked beta-glucan in the cell wall of the starchy endosperm. Isoenzyme II of the (1-3,1-4)-beta-glucanase forms large single crystals when a protein solution is equilibrated against 20% (w/w) polyethylene glycol 8000 at acidic pH using the hanging drop vapour diffusion method. The crystals diffract to better than 2 A resolution. They are monoclinic, space group P2(1), with cell dimensions a = 49.58 A, b = 82.99 A, c = 77.56 A and beta = 104.36 degrees. Two protein molecules are estimated to fill the asymmetric unit. PMID- 8355265 TI - Crystallization of bacteriophage fr and its recombinant capsids. AB - Single crystals of Escherichia coli bacteriophage fr and its recombinant capsids have been obtained by the vapour diffusion technique in the presence of ammonium sulphate. They diffract X-rays to at least 3.5 A. Electron microscopic observation of the crystals revealed a three-dimensional lattice of particles with RNA phage morphology and dimensions. PMID- 8355267 TI - A model of the three-dimensional structure of ice nucleation proteins. AB - Bacterial ice-nucleation proteins are among the most active natural ice nucleants and can reduce the supercooling point of water in plants, thereby reducing the ability of sensitive plants to avoid damaging ice formation. We describe a structural model for bacterial ice-nucleation proteins based on molecular modelling. This model predicts a largely planar extended molecule, with one side serving as a template for orienting water into an ice lattice and the other side interacting with the membrane. The model also predicts that single molecules can form aggregates of unlimited size by interdigitation. PMID- 8355266 TI - Crystallization of a genetically engineered water-soluble primary penicillin target enzyme. The high molecular mass PBP2x of Streptococcus pneumoniae. AB - A genetically engineered water-soluble derivative of PBP2x of Streptococcus pneumoniae has been produced, purified and crystallized in a form suitable for X ray diffraction analysis. The best crystals have been grown at 15 degrees C, from solutions containing 8% polyethylene glycol 10,000 at pH values ranging from 3.9 to 6.0. These crystals diffract to a resolution of 3.5 A and have a space group P6(1)22 (or enantiomorph) with unit cell dimensions of a = b = 162.2 A, c = 171.8 A, alpha = beta = 90 degrees, gamma = 120 degrees. The molecular mass and cell dimensions suggest that there is one molecule of enzyme per asymmetric unit. The breakdown of a chromogenic cephalosporin derivative diffused into a crystal reveals clearly that the enzyme is active in the crystalline state. PMID- 8355268 TI - The phase transition between a compact denatured state and a random coil state in staphylococcal nuclease is first-order. AB - Three mutants of staphylococcal nuclease containing a tryptophan substitution have been examined in the full length (149 residues) protein and in a large fragment (residues 1 to 136). The large fragments are not in the native state and are a good model of the denatured state. However, these large fragments do show signs of residual structure that breaks down upon titration with guanidine hydrochloride. They share some similarities with what has become known as the molten globule state. The thermal unfolding of these mutant fragments was followed by tryptophan fluorescence. Tryptophan fluorescence was treated as an order parameter and analyzed to determine the order of the observed transition. The critical exponent of the order parameter as the transition temperature is approached is significantly higher than the value of 1/2 predicted by mean field theory for a second-order transition and is similar to that observed for the transition of the full length, wild-type, protein. This is strong evidence that the breakdown of this intermediate compact denatured state is a cooperative, first-order phenomenon. PMID- 8355269 TI - RIP60 dimers and multiples of dimers assemble link structures at an origin of bidirectional replication in the dihydrofolate reductase amplicon of Chinese hamster ovary cells. AB - We show assembly of low and high multimers of HeLa cell nuclear protein, RIP60, at the origin of bidirectional replication (OBR) identified by Burhans, Vassilev, Caddle, Heintz and DePamphilis in Chinese hamster ovary cells. RIP60 binds a 5' ATT-3' reiterated sequence downstream of the OBR and a second, homologous ATT sequence of opposite orientation situated within the OBR zone. Specifically bound structures were studied by conventional electron microscopy (EM) and quantitative scanning transmission electron microscopy (STEM). Dimers and multiples of dimers link the downstream binding site that overlaps a bent DNA sequence and the homologous upstream OBR sequence, looping out 700 bp of intervening DNA. Superposed dimers are found at individual unlinked sites, stabilized presumably through protein-protein interaction, and such superposition appears to occur also in the basic link structure. Along the loop, single crossovers and extended twists are observed by conventional EM. By STEM, loop DNA is laterally compacted, with diameter and mass equivalent to double-duplex DNA strands. Supercoiled 736 bp and 5243 bp circular DNAs assume similar laterally compacted geometries that are mostly absent from relaxed forms. These observations parallel the compacted, interwound superhelices viewed by cryo-electron microscopy in vitrified solutions containing magnesium ions, and provide structural evidence in agreement with that from conventional EM for superhelical tension in RIP60 loop DNA. Loop superhelicity could arise as a topological response to linking and suggests a functional role for link formation. PMID- 8355270 TI - Homologous DNA targeting with RecA protein-coated short DNA probes and electron microscope mapping on linear duplex molecules. AB - We demonstrate that RecA protein-coated, short single-stranded DNA probes paired with a specific homologous DNA sequence in a linear duplex target molecule and accurately targeted the selected DNA sequence. RecA protein-coated complementary ssDNA probes were reacted with linear duplexes, and the homologously paired molecules were observed by electron microscopy. The sites of interaction between the RecA protein-coated DNA probes and the uncoated duplex DNA targets were directly visible on individual target DNA molecules by high-resolution darkfield electron microscopy, without chemical fixation or sample shadowing. The efficiency and specificity of pairing were verified with 446 and 222 base single stranded DNA probes that shared no homology with one another, and several linear duplex target DNAs with their respective probe homology sites at different locations with respect to the ends of the double-stranded DNA molecules. Measurements of the position of RecA protein-coated probes paired to individual target molecules, observed at high magnification, showed that DNA probes specifically paired at their corresponding homologous target sequences. This RecA protein-mediated DNA mapping method allows homologous sequence positioning and gene mapping on individual double-stranded DNA molecules. Targeting reactions in which two different probe/target sites were 900 bases apart on a single duplex target molecule allowed both sites to be mapped in the same targeting reaction; although targets displaying both probes simultaneously were seen much less frequently than expected. The possible torsional or mechanistic constraints related to these reactions are briefly discussed. PMID- 8355271 TI - Modulation of P(RM) activity by the lambda PR promoter in both the presence and absence of repressor. AB - When the transcription startsites of the phage lambda promoters PRM and PR are separated by 82 bp (the wild-type spacing), mutating PR increases the rate of open complex formation at PRM at all RNA polymerase (RNAP) concentrations tested in vitro. This is reflected in a fourfold increase in kappa f (the rate constant for isomerization of closed to open complexes) and a threefold decrease in KB (the equilibrium constant for formation of closed complexes). These effects of mutating PR resemble qualitatively those we observed when the separation between the two promoters was decreased by a single base-pair, but are quantitatively less dramatic. Although mutating PR has the additional effect of uncovering a weak promoter, P alpha, which overlaps both PRM and PR, the presence of P alpha does not account for the effects of PR mutations on open complex formation at PRM. In fixed-time assays at a single RNAP concentration, repressor stimulated PRM approximately threefold on a PR- template, indicating that activation is mediated substantially by a direct interaction between repressor and RNAP. That is, activation of PRM is not merely an indirect consequence of repressing PR. Kinetic data confirm this conclusion. In a PR- genetic background, repressor increased kappa f six- to eightfold and decreased KB approximately twofold. Similar results were obtained when OR3 was mutated, indicating that the effect on KB is not due to repressor binding to OR3. Thus, repressor causes a significant increase in the rate of open complex formation at PRM even when PR is inactive. On a PR+ template, 75 nM repressor stimulated PRM by increasing kappa f eightfold, with no effect on KB, which agrees with previous results. However, increased repressor concentrations stimulated kappa f by an additional factor of two to four, indicating that previous experiments underestimated the effect of repressor on kappa f. At the same time, increasing the repressor concentration decreased KB for PRM on a wild-type template. At the highest repressor concentration tested (275 nM), KB decreased 15-fold, presumably due to OR3 mediated repression of PRM. However, at an intermediate repressor concentration (170 nM) values of kappa f and KB for PRM on a PR+ template were in close agreement with the corresponding parameters obtained on a PR- template. These data lead us to suggest that repressor causes a decrease in KB for PRM on both a PR+ and a PR- template independent of its ability to bind to OR3. PMID- 8355272 TI - Prediction of protein structure by evaluation of sequence-structure fitness. Aligning sequences to contact profiles derived from three-dimensional structures. AB - The problem of protein structure prediction is formulated here as that of evaluating how well an amino acid sequence fits a hypothetical structure. The simplest and most complicated approaches, secondary structure prediction and all atom free energy calculations, can be viewed as sequence-structure fitness problems. Here, an approach of intermediate complexity is described, which involves; (1) description of a protein structure in terms of contact interface vectors, with both intra-protein and protein-solvent contacts counted, (2) derivation of sequence preferences for 2 up to 29 contact interface types, (3) generation of numerous hypothetical model structures by placing the input sequence into a large set of known three-dimensional structures in all possible alignments, (4) evaluation of these models by summing the sequence preferences over all structural positions and (5) choice of predicted three-dimensional structure as that with the best sequence-structure fitness. Evolutionary information is incorporated by using position-dependent core weights derived from multiple sequence alignments. A number of tests of the method are performed: (1) evaluation of cyclic shifts of a sequence in its native structure; (2) alignment of a sequence in its native structure, allowing gaps; (3) alignment search with a sequence or sequence fragment in a database of structures; and (4) alignment search with a structure in a database of sequences. The main results are: (1) a native sequence can very well find its native structure among a large number of alternatives, in correct alignment; (2) substructures, such as (beta alpha)n units, can be detected in spite of very low sequence similarity; (3) remote homologous can be detected, with some dependence on the set of parameters used; (4) contact interface parameters are clearly superior to classical secondary structure parameters; (5) a simple interface description in terms of just two states, protein-protein and protein-water contacts, performs surprisingly well; (6) the use of core weights considerably improves accuracy in detection of remote homologues; (7) based on a sequence database search with a myoglobin contact profile, the C-terminal domain of a viral origin of replication binding protein is predicted to have an all-helical fold. The sequence-structure fitness concept is sufficiently general to accommodate a large variety of protein structure prediction methods, including new models of intermediate complexity currently being developed. PMID- 8355273 TI - The phage 434 OR2/R1-69 complex at 2.5 A resolution. AB - The crystal structure of the DNA-binding domain of bacteriophage 434 repressor (R1-69) in complex with a 20 base-pair DNA fragment has been determined to 2.5 A resolution. The DNA fragment contains the sequence of the OR2 operator site, which differs from the previously studied OR1 site at three of the variable six central base-pairs. Comparison of the two structures shows that the overall bent conformation of the DNA backbone as well as the pattern of DNA-protein interactions seen in the OR1/R1-69 complex are maintained in the OR2 complex. However, the conformations of the DNA base-pairs are different in the two structures. In particular, the central base-pairs of OR2/R1-69 structure are more co-planar than in OR1/R1-69, and there are no cross-strand "bifurcated" hydrogen bonds. These results show that binding of the protein causes operator DNA to adopt a particular, well-defined backbone conformation, and they reinforce the notion that the energetic cost of achieving this conformation, most likely different for different sequences, can determine, at least in part, the relative affinity of the repressor for different operator sites. PMID- 8355274 TI - Crystal structure of a porcine pancreatic phospholipase A2 mutant. A large conformational change caused by the F63V point mutation. AB - The highly homologous bovine and porcine pancreatic phospholipase A2 (85% amino acid residue identity) show a large conformational difference in the loop from residue 59 to 71. In bovine phospholipase A2 residues 59 to 66 adopt an alpha helix conformation, while residues 67 to 71 are in a surface loop. Residues 59 to 66 in the porcine enzyme have a random coil conformation, and residues 67 to 71 form a short 3(10)-helix. It has been suggested that most probably this conformational difference is caused by the substitution Val63 (bovine) to Phe63 (porcine) in the otherwise invariant loop 59 to 70. To test this hypothesis, a mutant porcine phospholipase A2 was constructed in which residue Phe63 was replaced by a Val. The activity of this F63V mutant towards aggregated substrates was about half the activity of wild-type porcine phospholipase A2, but significantly different from that of the bovine enzyme. The affinity for zwitterionic interfaces was found to be intermediate between porcine and bovine phospholipase. The mutation did not have any effect on the stability of the enzyme towards denaturation by guanidine.HCl. The F63V mutant was crystallized in space group P2(1)2(1)2(1) with cell dimensions a = 79.88 A, b = 65.23 A, c = 52.62 A, with two molecules per asymmetric unit. Its three-dimensional structure was solved by molecular replacement methods, and refined to a crystallographic R factor of 17.6% for all data between 10 and 2.2 A resolution. In one molecule the 58 to 71 loop is in very weak density, suggesting a high degree of disorder or flexibility. The conformation of the same loop in the other molecule could be determined unambiguously. It shows a conformation which resembles more that of bovine phospholipase A2 than that of porcine phospholipase. It is concluded that indeed the single F63V substitution causes a dramatic conformational change. PMID- 8355275 TI - Refined X-ray structures of haloalkane dehalogenase at pH 6.2 and pH 8.2 and implications for the reaction mechanism. AB - The crystal structure of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 has been refined at 1.9 A resolution at two different pH values, the pH of crystallization (pH 6.2) and the pH of optimal activity (pH 8.2), to final R factors of 16.8% and 16.4%, respectively. Both models show good stereochemical quality. Two non-glycine residues have main-chain torsion angles that are located outside the "allowed" regions in a Ramachandran plot. One of them is the nucleophilic residue Asp124, which, together with the two other active site residues His289 and Asp260, is situated in an internal, predominantly hydrophobic cavity. The other residue, Asn148, helps stabilize the conformations of two of these active-site residues, Asp124 and Asp260. Comparison of the models at pH 6.2 and pH 8.2 revealed one major structural difference. At pH 6.2, a salt-bridge is present between the N epsilon 2 atom of His289 and the O delta 1 atom of Asp124, while at pH 8.2, this salt-bridge is absent, indicating that the N epsilon 2 atom of the histidine residue is mostly deprotonated at the pH of optimum activity. This is in agreement with the putative reaction mechanism in which the O delta 1 atom of Asp124 performs a nucleophilic attack on the substrate, resulting in an intermediate ester. This ester is subsequently cleaved by a hydrolytic water molecule. The high-resolution data sets clearly show the exact position of this water molecule. It is in an ideal position for donating a proton to the N epsilon 2 atom of His289 and subsequently cleaving the covalently bound intermediate ester, releasing the alcohol product. Detailed investigation of both refined models showed a number of unusual structural features. Four out of 11 helices contain an internal proline residue other than in the first turn. Two other alpha helices have adopted in their central part a 3(10) conformation. A novel four residue turn between a helix and a strand, the alpha beta 4 turn, is located at the site of the bend in the central eight-stranded beta-sheet of the dehalogenase structure. PMID- 8355276 TI - Determination of the disulphide bonding pattern in proteins by local and global analysis of nuclear magnetic resonance data. Application to flavoridin. AB - This paper describes a new method for the elucidation of the disulphide bonding pattern in a protein from an initial set of unrefined nuclear magnetic resonance solution structures. The use of both local and global proton-proton nuclear Overhauser enhancement (NOE) distance information for the identification of the disulphide bridge network in cysteine-rich polypeptides was investigated by statistical analysis of the crystal structures of a selected group of proteins. There are six different types of inter-cysteine proton-proton distances which can potentially be used for the prediction of disulphide links. The uniqueness and the extent to which disulphide bonds could be identified by these distances was evaluated. Only NOEs between C beta H/C beta H and C alpha H/C beta H were shown to have positive predictive values for the characterization of disulphide links. Contrarily, the observation of an NOE between C alpha H and NH is a strong indication for the absence of a disulphide bridge between the two residues. The global analysis of the nuclear magnetic resonance data starts with the calculation of an initial set of conformers. First, pairing weights wij were assigned to all putative cysteine pairs in the protein according to a Gaussian type distribution function from the C beta-C beta interatomic distances. In a second step, all conceivable disulphide patterns were formed by an exhaustive combinatorial enumeration. Statistical weights were then assigned to all patterns from the weights of the participating cysteine pairs. This method was validated with protein crystal structures deposited in the Brookhaven Protein Data Bank having three or more cysteine residues. It was then used to determine the previously unknown disulphide bonding pattern of the 12 cysteine residues of flavoridin. PMID- 8355277 TI - The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet GP IIb-IIIa receptor. AB - The snake venom protein flavoridin, a polypeptide of 70 amino acid residues, is a potent inhibitor of blood platelet aggregation. It binds to cell-surface integrin receptors such as the fibrinogen receptor glycoprotein IIb/IIIa. The inhibitory properties of flavoridin have been attributed to the tripeptide segment Arg-Gly Asp (residues 49 to 51). This paper describes the determination of the three dimensional structure of flavoridin in aqueous solution based on two-dimensional nuclear magnetic resonance spectroscopy. A family of 18 conformers was selected to characterize the solution structure. The molecule comprises two structural domains, an N-terminal unit extending from residues 1 to 25, and a C-terminal unit from residues 26 to 70. Whereas the mutual spatial orientation of these regions is not well defined, each one is well organized within itself. The segment 26 to 70, which is homologous to the sequence of the snake toxins echistatin and eristostatin, shows an average value of 1.0 A for the root-mean square deviations of the backbone atoms among the 18 conformers. The structure of flavoridin consists essentially of non-repetitive elements such as tight turns and loops, whose location and conformation are characterized in this paper. With the exception of two short regions of antiparallel beta-sheet, no classic element of protein secondary structure is present. The six disulphide bridges, which have been mapped by applying a novel computational strategy (see accompanying paper), are the dominant organizational feature of the polypeptide fold of flavoridin. Two of the bridges are located in the N-terminal domain, three in the C-terminal domain and one connects the two structural units. The mobile RGD recognition sequence for integrins is located peripheral to the core region of the C-terminal domain at the most exposed end of a nine residue loop structure, which is attached to a short beta-sheet. The C terminus is close to this loop structure. PMID- 8355278 TI - Characterization of a triple helix-specific ligand. BePI (3-methoxy-7H-8-methyl 11- [(3'-amino)propylamino]-benzo[e]pyrido[4,3-b]indole) intercalates into both double-helical and triple-helical DNA. AB - A benzo[e]pyridoindole derivative, 3-methoxy-7H-8-methyl-11-[(3' amino)propylamino] -benzo[e]pyrido[4,3-b]indole (BePI), and its interactions with double and triple-helical DNA have been investigated by a variety of fluorescence, spectrophotometric, hydrodynamic and molecular modeling techniques. Binding to DNA stabilizes the doubly charged (+2) form of BePI, increasing the apparent pKa of the 10-NH proton by approximately 1 pH unit. Binding to DNA also quenches the fluorescence of BePI, with a greater extent of quenching upon binding triplex relative to duplex DNA. BePI preferentially binds (and stabilizes) triple-helical relative to double-helical DNA. This preferential binding is not restricted to triplexes containing solely T x A.T base triplets. In addition, BePI preferentially stabilizes the poly(dA).poly(dT) relative to the poly[d(A-T)].poly[d(A-T)] duplex. Viscosity studies demonstrate that, upon binding, BePI induces the unwinding of negative supercoils in the pBR322 plasmid, and increases the relative contour lengths of double and triple-helical polydeoxynucleotides. Fluorescence studies reveal that energy transfer occurs from polynucleotide bases to bound BePI molecules in both BePI/duplex and BePI/triplex complexes. In a BePI/triplex complex, an average of 4.8 bases appear to transfer excitation energy totally to a bound BePI molecule, while in various BePI/duplex complexes an average of only 2.5 bases appear to do so, indicating that energy transfer is more efficient in the former complex. Measurements of fluorescence quenching indicate that BePI is protected from quenching by acrylamide when bound to either double or triple-helical polynucleotides. The viscosity and fluorescence behavior of BePI are fully consistent with the conclusion that BePI intercalates into both double and triple-helical DNA. Molecular modeling studies suggest that stronger stacking interactions between intercalated BePI and adjacent bases in BePI/triplex relative to BePI/duplex complexes may account for the enhanced thermal stability of the former complex. PMID- 8355279 TI - Structure of human des(1-45) factor Xa at 2.2 A resolution. AB - The structure of a large molecular fragment of factor Xa that lacks only a Gla (gamma-carboxyglutamic acid) domain (N-terminal 45 residues) has been solved by X ray crystallography and refined at 2.2 A resolution to a crystallographic R-value of 0.168. The fragment identity was clearly established by automated Edman degradation. X-ray structure analysis confirmed the biochemical characterization and also revealed that the N-terminal epidermal growth factor (EGF)-like domain is flexibly disordered in crystals. The second EGF module, however, is positionally ordered making contacts with the catalytic domain. The overall folding of the catalytic domain is similar to that of alpha-thrombin, excluding the insertion loops of the latter with respect to simpler serine proteinases. The C-terminal arginine of the A-chain interacts in a substrate-like manner with the S1 specificity site of the active site of a crystallographically neighboring molecule. Based on this interaction and the structure of D-PheProArg methylene thrombin, a model of the commonly used dansylGluGlyArg methylene inhibitor-factor Xa interaction is proposed. The region of factor Xa corresponding to the fibrinogen recognition site of thrombin has a reversed electrical polarity to the anion binding fibrinogen recognition site of thrombin but possesses a site similar to the Ca2+ binding site of trypsin and other serine proteinases. The structure of the C-terminal EGF domain of factor Xa is the first to be determined crystallographically. Its folding has been comprehensively compared with similar domains determined by NMR. Although the A-chain makes 44 contacts at less than 3.5 A with the catalytic domain, only 16 involve the EGF module. In addition, the A-chain makes 30 intermolecular contacts with a neighboring catalytic domain. PMID- 8355280 TI - Secondary structure and temperature-induced unfolding and refolding of ribonuclease T1 in aqueous solution. A Fourier transform infrared spectroscopic study. AB - The secondary structure of ribonuclease T1 (RNase T1) in aqueous solution and its temperature-induced structural changes have been investigated by Fourier transform infrared (FT-IR) spectroscopy. 13 to 14% alpha-helix and 32 to 33% beta sheet were estimated from the resolution-enhanced FT-IR spectra, in agreement with the crystal structure which indicates 16% alpha-helix and 35% beta-sheet. Specific IR-marker bands are assigned to the different beta-sheet structures, to the slightly bent alpha-helix, and to beta-turn and irregular conformations present in RNase T1. The temperature dependence of the infrared spectra shows that the thermal unfolding and refolding of RNase T1 is fully reversible. This permitted the detailed analysis of structural changes that occur as a function of temperature by evaluating quantitatively the various secondary structure-related amide I band components and some amino acid side-chain vibrations as specific monitors. The secondary structure of RNase T1 is essentially retained in the temperature range between 20 and 50 degrees C. Significant perturbation of protein structure is initiated between 50 and 55 degrees C within regions of beta sheet structures while the alpha-helix remains virtually intact up to 55 degrees C suggesting a "premelting" of RNase T1. Between 55 and 60 degrees C, a highly co operative unfolding process is indicated by the simultaneous breakdown of all secondary structure components and by distinct changes of some specific side chain vibrations. An analysis of the amide I band contour of RNase T1 at 70 degrees C proves that the unfolded state is predominantly, but not completely, irregular or "random coil". Residual, turn-like structures persisting even in the unfolded state are suggested by minor, turn related band components in the amide I region. From IR-spectra collected along a linear temperature gradient, intensity/temperature and frequency/temperature profiles were constructed using some peptide backbone and amino acid side-chain marker bands as local, structure sensitive monitors. From these profiles individual transition temperatures tm and transition enthalpies delta H (van't Hoff) were calculated. The tm and delta H values revealed a small but distinct hysteresis between repetitive cycles of unfolding and refolding of the protein, suggesting slow refolding kinetics of RNase T1. Furthermore, the various infrared "marker bands" indicate a slightly different response towards temperature increase/decrease for different regions of the protein. The data demonstrate that infrared spectroscopy permits both the detailed analysis of structural changes occurring in a protein as a function of temperature and the determination of thermodynamic parameters characterizing its folded/unfolded state transition. PMID- 8355281 TI - Crystallization and preliminary X-ray analysis of the DNA binding domain of the Hin recombinase with its DNA binding site. AB - The Hin recombinase catalyzes site-specific inversion of DNA. Chemical and genetic studies on Hin binding to the recombination sites indicates that both major and minor DNA groove interactions are critical. In order to determine the molecular nature of these interactions, we have crystallized a synthetically derived 52 amino acid peptide consisting of the DNA binding domain of Hin with a 14 base-pair oligonucleotide representing a recombination half-site. This communication presents preliminary diffraction and analysis of these cocrystals and a packing model for the complex within the crystal. PMID- 8355282 TI - Crystallization and preliminary X-ray diffraction analysis of crystals of Thermoascus aurantiacus xylanase. AB - Crystals suitable for high resolution X-ray diffraction analysis have been grown of the 29,774-Da protein, xylanase (1,-4-beta-xylan xylanohydrolase EC 3.2.1.8) from the thermophilic fungus Thermoascus aurantiacus. This protein, an endoxylanase demonstrates the hydrolysis of beta-(1-4)-D-xylose linkage in xylans and crystallizes as monoclinic pinacoids in the presence of ammonium sulphate buffered at pH 6.5, and also with neutral polyethylene glycol 6000. The crystals belong to space group P2(1) and have cell dimensions, a = 41.2 A, b = 67.76 A, c = 51.8 A; beta = 113.2 degrees. PMID- 8355283 TI - Preliminary crystallographic study of cyclohexadienyl dehydratase from Pseudomonas aeruginosa. AB - Single crystals of cyclohexadienyl dehydratase from Pseudomonas aeruginosa have been obtained by vapour diffusion from ammonium sulphate solution (pH 6.0) at 4 degrees C. The crystals belong to the tetragonal space group P4(3)2(1)2 or P4(1)2(1)2 with a = b = 105.5 A and c = 165.0 A. The asymmetric unit contains at least one dimeric protein molecule with M(r) = 72 kDa. The crystals diffract to 3 A resolution and are suitable for an X-ray analysis. PMID- 8355284 TI - Crystallization of a chitosanase from Streptomyces N174. AB - Chitosanases are produced by many soil fungi and bacteria to degrade chitosan present in fungal cell walls. Here, we report the crystallization of a 29,500 dalton protein with chitosan endo-hydrolase activity isolated from Streptomyces N174. The crystals were grown by vapor diffusion. They are mechanically strong and diffract to at least 1.9 A resolution. The crystals belong to the monoclinic space group P2(1) with unit cell parameters a = 56.4 A, b = 59.6 A, c = 86.1 A and beta = 96.6 degrees. Cell parameters and crystal density are consistent with two chitosanase molecules per asymmetric unit. PMID- 8355285 TI - A toxin that recognizes muscarinic acetylcholine receptors. Preparation and characterization of crystals suitable for structural analysis. AB - Muscarinic toxin 2 from Dendroaspis angusticeps has been crystallized by vapour diffusion, in sodium acetate using sodium thiocyanate as a precipitant. Trigonal crystals (space group P3(1)21 or P3(2)21) have been obtained. The unit cell parameters are a = b = 64.2 A and c = 37.1 A. The presence of one molecule per asymmetric unit is estimated. PMID- 8355286 TI - Preliminary crystallographic studies on scytalone dehydratase from Magnaporthe grisea. AB - Magnaporthe grisea are pathogenic, directly penetrating fungi which cause rice blast disease. Isolated, non-pathogenic mutant strains which are defective in the biosynthesis of dihydroxynapthalene-derived melanin fail to infect host plants and have been shown to lack certain key enzymes in melanin biosynthesis. One such enzyme is scytalone dehydratase that converts scytalone to 1,3,8-trihydroxy naphthalene. Crystallization trials of scytalone dehydratase were undertaken with the expectation that structural information on this enzyme would facilitate design of high affinity inhibitors which might find use in the control of rice blast disease. We now report that recombinant scytalone dehydratase, complexed with a tight binding inhibitor, has been crystallized with PEG 4000 as a precipitant. The crystals are trigonal and belong to the space group P321 with the cell dimension: a = b = 75.5 A, c = 73.8 A. The observed diffraction extends to 2.5 A. Analysis of the packing in the cell suggests that scytalone dehydratase forms a symmetric trimer. These results are consistent with sedimentation equilibrium experiments indicating that the solution aggregation state of scytalone dehydratase was trimeric over a 24,000-fold concentration range. PMID- 8355287 TI - Teratogenicity study (segment II) of recombinant granulocyte-macrophage colony stimulating factors (LBD-005) in rats. AB - A teratogenicity study was carried out in Sprague-Dawley rats subcutaneously injected recombinant Granulocyte-Macrophage Colony Stimulating Factors (LBD-005), the growth of stem cell and the development of the hematopoietic cell, at dose levels of 250, 500 and 1000 micrograms/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offspring was observed. The incidences of external, internal and skeletal anomalies were not significantly increased in the fetuses of any treated groups. Recombinant GM-CSF caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offsprings. PMID- 8355288 TI - Peri- and postnatal study (segment III) of recombinant granulocyte-macrophage colony stimulating factors (LBD-005) in rats. AB - A perinatal and postnatal study was carried out in Sprague-Dawley rats subcutaneously injected recombinant Granulocyte-Macrophage Colony Stimulating Factors (LBD-005), the growth of stem cell and the development of the hematopoietic cell, at dose levels of 250, 500 and 1000 micrograms/kg/day for a period from day 17 of gestation to day 21 after delivery. All pregnant dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal and skeletal anomalies were not significantly increased in the F1 and F2 fetuses of any treated groups. Recombinant GM-CSF caused no effects on parturition, lactation, postnatal growth and differentiation, behaviour and reproductive ability of the male and female offsprings. PMID- 8355289 TI - An acute toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats. AB - The acute toxicity of a recombinant human interferon alpha A (code name: LBD-007) was evaluated in both sexes of Sprague-Dawley rats, 5 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results, LBD 007 was not considered to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD50 values in rats would be > 48 x 10(8) IU/kg in the study of oral administration and > 24 x 10(8) IU/kg in the study of subcutaneous or intravenous administration. PMID- 8355290 TI - A 4-week subcutaneous toxicity study of recombinant human interferon alpha A (LBD 007) in Sprague-Dawley rats. AB - Recombinant human interferon alpha A (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 6, 12 and 24 x 10(6) IU/kg of body weight five days per week for 4 weeks to evaluate the subchronic toxicity. 20 to 50% of rats except the male control group showed minimal to mild, focal to multifocal renal mineralization. Whether renal mineralization is related to the test substance is not elucidated. Male rats dosed at 24 x 10(6) IU/kg showed the decrease of the absolute kidney weights and the increase of the brain relative weights. Female rats dosed at 24 x 10(6) IU/kg showed the increase of the absolute and relative ovary weights, and the decreases of specific gravity, bilirubin and urobilinogen in urine. However, no drug related changes were noted in clinical findings, body weights, food consumption, water consumption, hematology, blood clinical chemistry and necropsy findings. Based on the results it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon alpha A (LBD-007) in rats is (6 approximately 12) x 10(6) IU/kg. PMID- 8355291 TI - A 6-month subcutaneous toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats. AB - Recombinant human interferon alpha A (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 3, 6 and 12 x 10(6) IU/kg of body weight six days per week for 6 months to evaluate the chronic toxicity. Male rats dosed at 12 x 10(6) IU/kg for 26 weeks showed a decrease of ketone body in the urine, and female rats dosed at 12 x 10(6) IU/kg for 26 weeks showed a decrease of serum alkaline phosphatase. Microscopic changes with remarkable incidence were nephropathy, renal mineralization and ultimobranchial cysts of the thyroid gland in all groups of both sexes of rats. These changes were not considered to be drug-related toxicity because they appeared to be minimal, occasionally mild in severity and did not have dose dependency as well as clinical significance. In general, no drug-related change was noted in clinical findings, body weights, food consumption, water consumption, hematology, organ weights and necropsy findings. Based on the results, it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon alpha A (LBD-007) in rats would be 6 x 10(6) IU/kg. PMID- 8355292 TI - A study on antigenicity of recombinant human interferon alpha A (LBD-007) in mice and guinea pigs. AB - Antigenicity of recombinant human interferon alpha A (LBD-007), a newly developed drug for myeloid leukemia and hepatitis, was investigated in mice and guinea pigs. The following results were obtained: 1. Mice showed no production of antibodies against LBD-007 inoculated with aluminum hydroxide gel (alum) as an adjuvant, judged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-007 only and of LBD-007 with complete Freund's adjuvant (CFA) as an adjuvant did not produce positive reactions in any of homologous active systemic anaphylaxis (ASA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in both of PCA and ASA. 3. These findings suggested that LBD-007 has no antigenic potential in mice or guinea pigs. PMID- 8355293 TI - Focused ultrasound examinations by surgeons: the time is now. PMID- 8355294 TI - Should motorcycles be operated within the legal alcohol limits for automobiles. AB - A motorcycle simulator was used to assess operating performance of 14 experienced motorcyclists with varying breath alcohol concentrations. Riding error scores in three defensive and evasive maneuvers plus distance traveled in a standard time period were documented at baseline and at predetermined intervals following controlled alcohol consumption. The results revealed a positive correlation between total errors and breath alcohol concentrations within a range well below the commonly accepted legal limit of intoxication of 0.10 mg/dL. There was a highly significant increase (p < 0.0055) in an operator's tendency to leave the roadway (an error that is frequently fatal for motorcyclists), as well as a reduction in ability to complete a timed course. Moreover, performance errors increased while operators were "sobering up," a dramatic finding not heretofore established in previous studies. Since the present definition of the legal limit of intoxication for motorcyclists is based on automobile studies, noted increases in reaction time and performance errors support the hypothesis that "legal alcohol levels" should be lowered for motorcycle operators. PMID- 8355295 TI - Femoral catheters and deep venous thrombosis: a prospective evaluation with venous duplex sonography. AB - Femoral vein cannulation (FVC) with 8.5F Swan-Ganz catheter introducers allows expeditious intravenous access and rapid volume infusion; however, the incidence of associated iliofemoral deep venous thrombosis (DVT) is unknown. Trauma patients (n = 76) requiring unilateral FVC were prospectively entered into a study where they were resuscitated via FVC and serially evaluated with bilateral venous duplex sonography (VDS). The incidence of DVT in catheterized femoral veins was compared with that in uncatheterized femoral veins. Catheters were removed promptly and VDS was performed within 24 hours and weekly for 1 month. Iliofemoral DVTs were identified in 11 of the 76 patients (14%). Iliofemoral DVTs occurred on the cannulated side in 9 (81.8%) compared with 2 (18.2%) on the uncannulated side (p < 0.05). We conclude that the use of the 8.5F FVC is associated with an increased incidence of DVT and that despite its convenience, this technique should not be routine. PMID- 8355296 TI - Endoscopic retrograde cholangiography in the nonsurgical management of blunt liver injury. AB - Injury to the intrahepatic bile duct has not been routinely examined in patients with blunt liver injury, despite the risk of formation of a biloma and hemobilia. In this study we examined the role of endoscopic retrograde cholangiography (ERC) in the evaluation of blunt liver injuries. Sixty-four of 106 (60.3%) patients with blunt hepatic injuries, admitted from April 1986 through March 1992, were managed nonsurgically; ERC was performed in conjunction with computed tomographic (CT) scanning to rule out injury to the bile duct in 28 patients. Injury to the bile duct was detected in six patients (21.4%), five of whom developed a biloma. Patients with hepatic parenchymal injuries that were observed on the CT scans were at greatest risk for injury to the intrahepatic bile duct, and our data suggested that the incidence of injury to the intrahepatic bile duct after blunt hepatic trauma is higher than previously reported. Patients with serious hepatic parenchymal injuries who are candidates for nonsurgical management should be considered for ERC to exclude the possibility of injury to the bile duct. PMID- 8355297 TI - Establishment of accurate incidence rates for head and spinal cord injuries in developing and developed countries: a capture-recapture approach. AB - Prevention of head and spinal cord injuries is defined as a reduction in the incidence of these disabilities. Accurate incidence data are fundamental to any prevention program. The current approaches toward determining incidence rates for head and spinal cord injuries are summarized. Previous research has focused on passive surveillance systems and population-based registries. An alternative system for monitoring the incidence of head injuries is discussed that uses a surveillance methodology called capture-recapture. This method employs multiple population-based sources to identify cases and uses the cases that overlap between the sources to estimate the degree of undercount in the population. This estimate in turn is used to produce an ascertainment-corrected incidence estimate. Through the use of methods such as capture-recapture, accurate monitoring of the incidence of head and spinal injuries across developing and developed countries is indeed feasible. PMID- 8355298 TI - Mortality from accidental falls among the elderly in the United States, 1962 1988: demonstrating the impact of improved trauma management. AB - Falls in elderly persons primarily occur because of increasing intrinsic frailty rather than extrinsic environmental hazards. Thus declining mortality from accidental falls in the elderly predominantly reflects improved trauma management rather than injury prevention. Mortality attributed to accidental falls among individuals aged 60 to 85 years in the United States from 1962 through 1988 was analyzed using the Strehler-Mildvan modification of the Gompertz relationship of aging and mortality. This method of analysis can be used to define a disorder specific age at which etiopathogenic influences are directly proportional to the mortality rate. From 1962 through 1988, the mortality rates (per 100,000) from accidental falls in the United States declined 63.5% (from 165.6 to 60.4) among men at age 83.4 years, and declined 76.3% (from 86.2 to 20.4) among women at age 77.5 years. This analysis suggests that trauma management, at the population level, was 2.74 times more effective in men and 4.22 times more effective in women at reducing mortality from accidental falls among the elderly in 1988 than in 1962. PMID- 8355299 TI - Internal fixation of open unstable pelvic fractures. AB - From 1980 through 1990 14 patients with severely complicated unstable fractures of the pelvis were treated. There were 13 men and one women (mean age, 28 years). Eight fractures also involved the acetabulum. The injuries were accompanied by anorectal (nine), urogenital (eight), vascular (three), and nerve (three) injuries. After resuscitation, fractures were stabilized immediately, preferably using internal fixation, notwithstanding fecal contamination in certain cases. Anorectal ruptures were treated with lavage of the distal colon and a divergent stoma. The urogenital lesions also were treated primarily. Two patients died early after treatment of accompanying injuries. Infectious complications were seen seven times. In one patient internal fixation broke down. All fractures healed with good functional results. At last follow-up examination all patients were continent for feces. It is concluded that early internal stabilization of these complex injuries achieves a low mortality rate and good functional results. Immediate repair of urogenital and sphincter lesions, with concomitant divergent stoma and lavage of the distal colon, gives good results notwithstanding the risk of infectious complications. PMID- 8355301 TI - Trauma fellowship training: the insiders' perspective. AB - Trauma care is in a period of transition from care given by surgeons at the closest community hospital to care given by trauma specialists at trauma centers and within emergency medical systems. It has thus become increasingly important for the educational goals of trauma fellowship training to reflect the needs of the future system as well as the views of future practitioners. These views differ from those of surgical colleagues practicing trauma surgery, and the views of future trauma specialists should be considered during the formulation of training guidelines. This survey appears to be the first attempt to interpret the views of trauma fellows: 48 of the 83 fellows (57.8%) in the 1991-1992 national cohort responded. They made suggestions about their own training, including ways to increase surgical experiences and opportunities for academic pursuits, but gave no insight as to an appropriate mix of critical care training. Although critical care certification is a major attraction for fellowship training, the cohort does not want to be thought of as nonoperating surgical intensivists. A second year of fellowship training is seen as necessary for research and trauma systems-related studies. PMID- 8355300 TI - Surgical treatment of humeral shaft fractures--the Basel experience. AB - One hundred twenty seven patients with fractures of the humeral shaft were treated by open reduction and internal fixation using 4.5-mm dynamic compression plates (DCP). Seventy one osteosyntheses were performed primarily, 36 following attempted closed reduction, and 20 secondarily after a failed conservative treatment of about 8 weeks. A primary radial nerve palsy was present in 19 patients, and appeared subsequently in four additional patients. One hundred two of the 127 patients could be clinically and radiologically examined 1 year after internal fixation: 89 patients (87.3%) had excellent or good results with full functional recovery. Thirteen patients (12.7%) showed a limited range of motion of either the shoulder or elbow or both. This was mostly because of other fractures of the same limb or persistent neurologic impairment. We observed two transitory postoperative nerve palsies, five early failures of internal fixation because of technical errors, two pseudarthroses and four postoperative infections, which healed with one exception by suction drainage and early removal of the plate. We conclude that a correct plate fixation of humeral shaft fractures in a selected group of patients represents an alternative to conservative treatment with the advantage of greater patient comfort. PMID- 8355302 TI - Trauma center accreditation in Canada--a proposal: 1992 Presidential Address, Trauma Association of Canada. PMID- 8355303 TI - Psychosocial characteristics and follow-up of drinking and non-drinking drivers in motor vehicle crashes. AB - Eight hundred fifty-four consecutive motor vehicle crash (MVC) victims admitted from August 1, 1986, through August 31, 1989, were prospectively assessed including measurement of blood alcohol concentration (BAC). One hundred six in hospital interviews were conducted on competent consenting drivers > or = 18 years old; 22.9% (n = 22) of those who were BAC tested (n = 96) were positive for alcohol on admission. The blood alcohol concentration positive [BAC(+)] and the BAC negative (-) drivers differed significantly on the following variables; driver education [BAC(-) > BAC(+): p < 0.01], license suspension < or = 2 years before admission [BAC(+) > BAC(-): p < 0.01], frequency of self-reported intoxication in month before crash [BAC(+) > BAC(-): p < 0.05], driving within 2 hours of drinking < or = 1 month before admission [BAC(+) > BAC(-): p = 0.01] and self-reported driving with BAC > 17 mmol/L < or = 1 month before admission [BAC(+) > BAC(-): p < 0.01]. Follow-up interviews (n = 106) were conducted 1 year after discharge; drivers originally testing BAC(+) were more likely to drive within 2 hours of drinking (p < 0.05), and were more likely to admit to driving with a BAC > 17 mmol/L (p < 0.01). Original BAC(+) drivers were also more likely to report a subsequent MVC in the year following discharge (not statistically significant). There is a need to develop an assessment system to identify high crash-risk drivers and establish rehabilitation programs to reduce crash recidivism. PMID- 8355304 TI - In vivo study of bleeding time and arterial hemorrhage in hypothermic versus normothermic animals. AB - This in vivo study confirmed impaired hemostasis during hypothermia in a swine model. Group I (normothermic, n = 8) and group II (hypothermic, n = 8) animals were anesthetized and instrumented for continuous peritoneal irrigation and monitoring of heart rate and blood pressure. The effects of hypothermia, hypotension, and inotrope on bleeding time and bleeding from two types of arterial injuries were evaluated. Our findings were that (1) bleeding time was significantly prolonged in hypothermic animals; (2) the differences in blood loss from partially torn artery (PTA) and completely cut artery (CCA) at both normothermic and hypothermic temperatures did not reach statistical significance; and (3) blood loss from PTA was greater than CCA when norepinephrine (Levophed) was infused to elevate blood pressure in hypotensive animals at normal core temperature. PMID- 8355305 TI - A comparison of right and left blunt traumatic diaphragmatic rupture. AB - Since right blunt traumatic diaphragmatic rupture (BTDR) is reported with increasing frequency, BTDR may be a disease in evolution. Data were collected on 59 left, 16 right, and five bilateral BTDRs at a level 1 trauma center. Patients with right BTDR had lower Glasgow Coma Scale (GCS) scores (p < 0.05), were more likely to be initially in hypovolemic shock, and were admitted directly from the field (p < 0.01). Left and right BTDRs were diagnosed from chest films in 37% and 0% of cases, respectively (p < 0.05). Diagnostic peritoneal lavage results were negative in 16% of left and left of 0% of right BTDRs. For right BTDRs, the liver was more likely to be injured (p < 0.001). The mortality rates were similar and ICU and hospital stays, complications, and duration of mechanical ventilation were similar for early survivors with right and left BTDRs. The clinical signs and symptoms, diagnosis, and surgical findings associated with right and left BTDR are different. PMID- 8355306 TI - A comparison between a Canadian regional trauma unit and an American level I trauma center. AB - Although there has been recent comparison of the Canadian and American health care systems, the issue of trauma has received little attention. Data were collected on all adult motor vehicle crash (MVC) victims admitted to the Sunnybrook Trauma Unit (CAN), Toronto, Canada, and the R Adams Cowley Shock Trauma Center (USA), Baltimore, Maryland from July 1986 through July 1990. Similar MVC victims at CAN and USA had equivalent mortality rates with similar discharge dispositions (p = NS), but patients at USA were twice as likely to be admitted to the ICU and had longer ICU stays (p < 0.01). The hospital-based cost for an average MVC patient at CAN was significantly less than for an average patient at USA and professional charges were at least five times greater at USA. This study provides some insight into the differences in trauma care between Canada and the United States. PMID- 8355308 TI - Priorities in the management of multiple trauma: intracranial versus intra abdominal injury. AB - Setting priorities in the management of patients with suspected injuries to both the head and the abdomen is difficult and depends on the likelihood of different injuries. Eight hundred trauma patients were retrospectively reviewed to determine the likelihood of a surgically correctable cerebral injury. All 800 patients, at the time of initial evaluation, were thought to have potentially correctable injuries to both the head and the abdomen. Of these, 52 had a head injury requiring craniotomy; 40 required a therapeutic celiotomy. Only three patients required both craniotomy and therapeutic celiotomy. There were more cases of delay in therapeutic celiotomy because of negative results of computed tomographic (CT) scanning of the head (13 cases) than there were delays in craniotomy because of nontherapeutic celiotomy (four cases). Need for craniotomy, based on emergency department evaluation, was indicated by the presence of lateralizing neurologic signs. Low Glasgow Coma Scale score, anisocoria, fixed/dilated pupils, loss of consciousness, facial or scalp injuries, and age were of no independent value in predicting the need for craniotomy. CONCLUSIONS: Patients with surgically correctable injuries of both the head and the abdomen are rare. In stable patients with altered mental status and potential injuries to both the head and the abdomen, the abdomen is best evaluated first by diagnostic paracentesis. If paracentesis does not return gross blood, CT scanning of the head should be done.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355307 TI - Prospective comparison of diagnostic peritoneal lavage, computed tomographic scanning, and ultrasonography for the diagnosis of blunt abdominal trauma. AB - From January through December 1990, a prospective study comparing the accuracy of diagnostic peritoneal lavage (DPL), abdominal computed tomographic (CT) scanning, and abdominal ultrasonographic (US) scanning was carried out. Patients with stable vital signs following their initial resuscitation coupled with equivocal physical examination findings received both CT and US scanning. A DPL was then done. If any of these three examinations produced positive findings, a laparotomy was done and the surgical findings were compared with the results of the diagnostic studies. Fifty-five patients were studied (44 men, 11 women), with a mean age of 43 years and a mean ISS of 18.5 +/- 10.5. The sensitivity, specificity, and accuracy were 100%, 84.2%, and 94.5% for DPL, 97.2%, 94.7%, and 96.4% for CT scanning, and 91.7%, 94.7%, and 92.7% for US scanning. Problems do exist in identifying isolated small intestinal perforations with ultrasonography. Since more and more trauma centers are using ultrasonography in the emergency department as a screening method in the management of patients with blunt abdominal trauma, it is important to avoid overestimating its capability. Frequent re-evaluation of the patient's condition, repeat ultrasonographic scans, diagnostic peritoneal lavage, and CT scanning are complementary and important in the diagnosis of blunt abdominal trauma. PMID- 8355309 TI - Renal gunshot wounds: methods of salvage and reconstruction. AB - Over the past 14 years, 2079 patients have been seen at our institution with renal trauma. Of these, 84 sustained gunshot wounds (81 unilateral, 3 bilateral; a total of 87 renal units). We evaluated this group to characterize the nature of their injuries and establish a methodology for renal salvage and reconstruction. Preoperative radiographic staging was performed with excretory urography (IVP) or computed tomographic (CT) scanning. The injuries were classified into five categories: 16 contusions (18.4%), 12 minor lacerations (13.8%), 44 major lacerations (50.5%), six vascular injuries (6.9%), and nine combination laceration and vascular injury (10.3%). Most patients had multiple organ injuries, with 79 requiring associated surgical procedures (94%). The mean injury Severity Score (ISS) was 26.7 (range, 4-59). Based on radiographic and clinical staging criteria, 69 renal injuries were surgically explored (79.3%), and 12 patients underwent nephrectomy (13.8%). Forty-six renal units were reconstructed (66.6%) by various methods, including renorrhaphy, omental pedical flaps, mesh or peritoneal patch grafts, partial nephrectomy, and vascular repair. Overall, 75 renal units were salvaged (86.2%). Early renal vascular control was achieved in all patients who underwent renal exploration. Follow-up functional studies were done in 24 (28.5%): none had delayed nephrectomy or postinjury hypertension. Overall, 79 patients survived (94%); however, mortality was not related to renal injury. These findings suggest that aggressive radiographic staging coupled with early vascular control and careful selection of reconstructive techniques can ensure a high renal salvage rate in patients with renal gunshot injuries. PMID- 8355310 TI - Vascular complications of continuous arteriovenous hemofiltration in trauma patients. AB - Continuous arteriovenous hemofiltration (CAVH) has recently become useful in the treatment of acute renal failure following trauma. It allows continuous volume removal and avoids the acute hemodynamic changes often seen with hemodialysis. To determine the risks of CAVH catheters, the records of trauma patients undergoing CAVH from August 1989 through May 1992 were reviewed. Of 4685 trauma patients, 29 developed renal failure requiring dialysis, with 26 managed with CAVH. Vascular access was obtained via 126 percutaneous 8F femoral arterial and venous catheters (64 arterial, 62 venous) and four Scribner shunts. There was a total of 309 CAVH D days, with an average of 11.9 days per patient. Complications included one femoral arteriovenous fistula, one pseudoaneurysm, and one deep venous thrombosis, resulting in a 3.1% (2 of 64) arterial complication rate and a 1.6% (1 of 62) venous complication rate. The incidence of arterial complications compares with that of angiography, but complications were major and required surgery. Alternative techniques such as continuous venovenous hemofiltration may prove beneficial. PMID- 8355311 TI - Candiduria as an early marker of disseminated infection in critically ill surgical patients: the role of fluconazole therapy. AB - The significance of candiduria in critically ill patients remains unclear. It may represent harmless colonization or a potentially life-threatening infection. We analyzed 47 patients in the surgical intensive care unit (SICU) (trauma: 20, general surgery: 15, neurosurgery: 12) who had candiduria, defined by a colony count greater than 100,000/mL. Twenty-seven of these patients were studied retrospectively. Twenty were evaluated prospectively. All patients were receiving broad-spectrum antibiotics for bacterial infections. Retrospective group: ten patients (group A) did not develop disseminated candidiasis, whereas 17 patients (group B) did. Group B had higher APACHE II scores on admission (13.4 +/- 7.8) and at the time of candiduria (13.7 +/- 4.4) when compared with group A [admission: 5.0 +/- 4.6; candiduria: 6.7 +/- 3.6 (p < 0.02)]. In group B, disseminated candidiasis was not diagnosed and treated until 9.9 +/- 4.4 days after development of candiduria. Prospective group: twenty patients with candiduria were treated with systemic fluconazole (group C) at the time of candiduria. The APACHE II scores of group C on admission (12.8 +/- 3.9) and at the time of candiduria (10.5 +/- 4.0) were comparable with those of group B. No patient in Group C developed disseminated candidiasis. The septic mortality rates of groups A, B, and C were 0%, 53%, and 5%, respectively (p < 0.05-0.0001). In patients exhibiting ongoing sepsis and organ failure (high APACHE scores), candiduria may be an early indicator of systemic infection. Diagnosis of disseminated infection and its treatment may be delayed if conventional criteria for candidiasis (positive blood cultures, multiple site isolation) are awaited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355312 TI - Computed tomography in the management of blunt thoracic trauma. AB - Computed tomographic (CT) scanning has proved to be valuable in evaluating the head and abdomen of victims of blunt trauma; CT scans of the thorax often are obtained on patients with blunt torso trauma, but their value for this purpose is unclear. We conducted a prospective study to evaluate the role of chest CT scanning in thoracic trauma. Hemodynamically stable patients at least 18 years old with an estimated Abbreviated Injury Scale--Thorax score of 2 or greater underwent a contrast-enhanced CT scan of the chest, usually in conjunction with CT scans of the head, abdomen, or both. Thirteen patients were dead on arrival, 14 required emergency surgical procedures, and 13 were too unstable to undergo chest CT scan. Thirty-three patients were not included because they refused to participate or the protocol was not followed. Forty-six men (69%) and 21 women with a mean age of 42.7 years completed the study. Sixty-one were injured in motor vehicle crashes, four were injured in falls, and one each was injured by assault and by crushing forces. Injury Severity Scores ranged from 4 to 45, with a mean of 20.5. Four patients died (6%), three from head injury and one from multiple organ dysfunction. Chest roentgenography (CXR) was superior to CT scanning in identifying rib fractures, but CT scanning was more sensitive than CXR for pneumothorax, fluid collections, and infiltrates (p < 0.001); CT scanning also was more specific for aortic injury. Despite this quantitative superiority, the abnormalities missed by CXR but identified by CT scanning infrequently led to a change in management.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355313 TI - Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients. AB - Combination therapy for nosocomial pneumonia with a beta-lactam and aminoglycoside is widely accepted because of synergy and reduction of resistant bacteria. This prospective study of 109 trauma patients (94 blunt, 15 penetrating) with nosocomial pneumonia was performed in consecutive phases. In phase 1, patients were randomized to an anti-pseudomonal third-generation cephalosporin--cefoperazone or ceftazidime. Gentamicin was added to each regimen in phase 2. The mean age of the patients was 37 years, the mean ISS was 31, and there were no differences among the four treatment groups relative to associated injuries. Patients receiving monotherapy had a 56% cure rate compared with 31% for combination therapy (p < 0.04). Persistence rates were similar in these two groups (15% and 20%), but superinfection was significantly higher in the combination group (49% vs. 28%; p < 0.04). The predominant superinfecting organism was methicillin-resistant Staphylococcus aureus (MRSA). Nine patients died (5% monotherapy, 10% combination), and eight had a superinfection. We conclude that monotherapy had a higher cure rate than combination therapy for empiric therapy of pneumonia in our trauma patients. Combination therapy failed because of superinfection (primarily MRSA). Emergence of MRSA may be from host overgrowth or plasmid-mediated induction of resistance, possibly caused by gentamicin. PMID- 8355314 TI - Isolated lateral traumatic dislocation of the radial head in a boy: case report. AB - Lateral traumatic dislocation of the radial head occurred in a 9-year-old boy with cubitus varus. Reduction of the dislocation and immobilization of the arm in flexion and supination in a plaster cast for 4 weeks were done and after 6 months the boy returned to school, with no problems in daily living. PMID- 8355315 TI - An in vitro evaluation of cocaine hydrochloride adsorption by activated charcoal and desorption upon addition of polyethylene glycol electrolyte lavage solution. AB - Cocaine body-packers and body-stuffers have become a common medical problem. Significant morbidity and mortality result when cocaine is absorbed from the gastrointestinal tract due to cocaine package compromise. The clinical prevention of gastrointestinal absorption of cocaine includes oral activated charcoal and/or whole bowel irrigation with polyethylene glycol--electrolyte lavage solution. This in vitro study investigates the maximal adsorptive capacity of activated charcoal for cocaine at varying activated charcoal:cocaine ratios, at pH 1.2 and pH 7.0, and the effect of polyethylene glycol--electrolyte lavage solution upon this binding. The percent adsorption of cocaine to activated charcoal was significantly better at pH 7.0 for all ratios of activated charcoal:cocaine tested and the maximal adsorptive capacity was 29% greater at pH 7.0 (273 micrograms/mg) than at pH 1.2 (212 micrograms/mg) (p < 0.05). Addition of polyethylene glycol--electrolyte lavage solution to the cocaine-activated charcoal slurry caused significant desorption of cocaine from activated charcoal at all pHs and ratios tested (except the 1:1 ratio at pH 7.0) and was most pronounced at pH 1.2. The addition of polyethylene glycol--electrolyte lavage solution to activated charcoal prior to adding cocaine solution further decreased the adsorption of cocaine to activated charcoal. This difference was significant at both pHs and all ratios tested except the 1:1 ratio at pH 1.2. The maximal adsorptive capacity of activated charcoal for cocaine at pH 1.2 was reduced 75% by pretreatment with polyethylene glycol--electrolyte lavage solution from 212 to 54.2 micrograms/mg, while at pH 7.0 the maximal adsorptive capacity was reduced by 11%, from 273 to 243 micrograms/mg. Polyethylene glycol--electrolyte lavage solution significantly reduces the adsorption of cocaine to activated charcoal particularly if the two are combined at a low pH prior to the addition of cocaine. The in vitro effects suggest that activated charcoal mixed in water should be administered first, followed by the polyethylene glycol--electrolyte lavage solution. PMID- 8355316 TI - Colorimetric and gas chromatographic procedures for glycolic acid in serum: the major toxic metabolite of ethylene glycol. AB - Monitoring of individuals poisoned with ethylene glycol involves analysis of ethylene glycol in serum. The objective of this procedure was to validate a colorimetric and gas chromatographic procedure for glycolic acid in serum. The colorimetric procedure requires no sophisticated instrumentation and has been shown to be specific for glycolic acid. A gas chromatographic procedure has also been developed involving methyl derivatization of glycolic acid and the internal standard (propionic acid). These methods have been used for the analysis of serum specimens from ethylene glycol poisoned patients. Glycolic acid has been recognized as the major toxic agent in ethylene glycol poisoning but current methods available do not allow analysis in a clinically relevant turnaround time. These two procedures allow glycolic acid quantitation by procedures readily set up in most clinical toxicology laboratories. PMID- 8355317 TI - Medications which can kill a toddler with one tablet or teaspoonful. AB - To identify medicinal preparations which can be fatal to a toddler upon ingestion of one standard dose unit, four major texts in medical toxicology were reviewed for reported cases of fatal poisoning in small children as well as for fatal doses in adults when no fatalities were reported in children. Using the Physicians Desk Reference, the largest dose unit commercially available for various drugs was identified. Subsequently, the number of dose units that have to be ingested by a toddler to cause fatality was calculated. To compare these data to the clinical reality, the annual reports by the American Association of Poison Control Centers National Collection System were reviewed between 1983-1989. Very few drugs are fatal for a 10 kg toddler upon ingestion of one commercially available dose unit. These include camphor, chloroquine, tricyclics, phenothiazines, quinine, methyl salicylate and theophylline. This short list of drugs was responsible for almost half (42%) of fatal cases following acute ingestion in young children (< 2 yrs) in the US between 1983-1989. Labelling of these drugs in a unique way may help decrease the number of serious and potentially fatal toxicities in small children. PMID- 8355318 TI - Radiopacity of household deodorizers, air fresheners, and moth repellents. AB - Household deodorizers and moth repellents are common agents implicated in many childhood poisonings. Their ingredients usually include either paradichlorobenzene or naphthalene compressed into a solid ball or another shape, sometimes with added essential oils and fragrances. Because medically naphthalene is a more important toxin than paradichlorobenzene, with hematologic and nervous system effects, clinicians often seek to discern which product has been ingested. We discovered fortuitously that a mothball swallowed by a retarded adult was radiopaque, and so designed an in vitro experiment to study the radiopacity of a variety of household deodorizers and products. Of 10 products screened for radiopacity by two radiologists, those containing paradichlorobenzene were consistently strongly radiopaque; those containing naphthalene were radiolucent. A third alternative ingredient which is used in some toilet bowl deodorizers, cetrimonium bromide, was also radiopaque. Radiopacity of paradichlorobenzene or cetrimonium bromide-containing products did not dissipate with time. We speculate that the halogen within the chemical structure of these compounds accounts for their radiopacity. We conclude that paradichlorobenzene-containing commercial products can be distinguished clinically from those containing naphthalene by the performance of an abdominal radiograph. PMID- 8355319 TI - When should dialysis be performed in lithium poisoning? A kinetic study in 14 cases of lithium poisoning. AB - Lithium kinetics were studied in 14 patients with lithium poisoning. Three patients were treated by hemodialysis. Serum lithium peak concentrations ranged between 1.4 and 9.6 mmol/L. The apparent mean serum half-life was 23.16 +/- 9 h, the mean total clearance was 26.5 +/- 13.3 mL/min and the mean renal clearance was 17.2 +/- 5.4 mL/min. The kinetic parameters were dependent on the duration of the study and on the type of the poisoning: acute, acute upon chronic or chronic. During the first 12 h after admission ten patients were in a distribution phase, three were in an elimination phase and one was in an absorption phase. The serum half-life during hemodialysis ranged from 3.6 to 5.7 h and hemodialysis clearance was 63.2 to 114.4 mL/min. The mean volume of distribution calculated in six cases was 0.63 +/- 0.09 L/kg. The evolution of the lithium pools showed a different kinetic pattern between the extra- and the intracellular pool which decreased more slowly. During hemodialysis the decrease of the extracellular pool was about twice that of the cellular pool. Among the factors which may modify lithium toxicity and kinetics, are the type of the poisoning, the presence of an underlying disease and renal impairment. No general and rigid indication for hemodialysis can be set, but the need for hemodialysis should be based on clinical and kinetic data determined during the 12 h following admission. PMID- 8355320 TI - Clinical features in 28 consecutive cases of laboratory confirmed massive poisoning with carbamazepine alone. AB - A retrospective study of consecutive cases of massive carbamazepine poisoning treated in an intensive care unit during the period 1981-1991 was performed, mainly to determine whether serum carbamazepine levels were predictive of toxicity. Out of a total of 51 admissions with a diagnosis of carbamazepine self poisoning, 28 (25 patients) were included. The reasons for exclusion were coingestion of other drugs (11 cases), incorrect diagnosis or inadequate information (6 cases), a peak observed serum concentration of carbamazepine below 76 mumol/L [18 mg/L] (4 cases), and lack of any documented serum carbamazepine assay (2 cases). The peak serum concentrations ranged from 78 to 285 mumol/L [18.4 to 67.4 mg/L]. It was found that serum levels equal to or above 170 mumol/L [40 mg/L] were significantly associated with an increased risk of serious complications such as coma, seizures, respiratory failure and cardiac conduction defects. In 60% of the 10 patients with a serum level > or = 170 mumol/L at least two of these symptoms occurred, in 50% at least three, and in 40% all four. There were two fatalities. Among the 16 patients (18 admissions) with a serum carbamazepine concentration below 170 mumol/L, only one was comatose and none had any of the other severe symptoms. It is concluded that serum carbamazepine levels accurately predict the severity of toxicity in massive carbamazepine poisoning in adults. PMID- 8355321 TI - Carbamazepine overdose: serum concentration less predictive in children. PMID- 8355322 TI - Effects of epinephrine and norepinephrine on hemodynamic parameters and arrhythmias during a continuous infusion of amitriptyline in rats. AB - Epinephrine and norepinephrine were evaluated in treatment of hemodynamic compromise in amitriptyline intoxication. One hundred and one male Wistar rats were monitored hemodynamically during amitriptyline intoxication and given one of three infusion rates (0.1, 0.5 or 5.0 mg/kg/min) of either epinephrine or norepinephrine. Sixteen rats served as controls and received only glucose after intoxication. Amitriptyline intoxication lowered mean arterial pressure, heart rate, left ventricular max dP/dt, and increased left ventricular end-diastolic pressure. All doses of norepinephrine and the two higher doses of epinephrine increased mean arterial blood pressure and left ventricular max dP/dt. Heart rate increased with both drugs, more with epinephrine, but not beyond pre-intoxicated levels at any dose. Left ventricular end-diastolic pressure was unaltered by both drugs. Malignant arrhythmias appeared in 7% of all animals, whereas a progressive decline of cardiac contractility caused cardiac arrest in 36% of all animals. This suggests that myocardial depression is the aspect most likely to cause death. At intermediate doses epinephrine resulted in significantly fewer arrhythmias and lower mortality compared to norepinephrine. We conclude that epinephrine and norepinephrine each appeared effective in reversing amitriptyline induced hemodynamic alterations. Epinephrine had fewer arrhythmogenic properties than norepinephrine and may be preferable to norepinephrine. PMID- 8355323 TI - Fatal inhalational isopropyl alcohol poisoning in a neonate. AB - A 37 weeks gestation, 1500 gram male infant with multiple dysmorphic features underwent surgery for gastroschisis several hours after birth. During post operative mechanical ventilation, 70% isopropyl alcohol was accidentally placed in the humidifier of the ventilator, resulting in an estimated 2 h exposure. While the baby seemed clinically stable, initial neurological examination was confounded by recent sedation and pancuronium paralysis. Initial post-operative hypotension was corrected with fluid administration and remained stable for the remainder of the clinical course. By 2 h post-exposure, he was moving, breathing spontaneously and opening his eyes. Isopropyl alcohol and acetone levels at 1, 6, 10 h post exposure were 31/10, 22/15, 15/20 mmol/L respectively. Isopropyl alcohol elimination t1/2 was 9.6 h. Dialysis or exchange transfusion were considered but due to their high risk and the stable infant condition, it was elected to continue with supportive care only. 12.5 h post-exposure, he suddenly became cyanotic, bradycardic, then asystolic. Resuscitation efforts were unsuccessful. To our knowledge, this is the youngest patient reported to have toxic inhalational exposure to isopropyl alcohol and the first report on isopropyl alcohol pharmacokinetics at this age. PMID- 8355324 TI - Butane inhalation and hemiparesis. AB - We report a case of hemiparesis resulting from acute intoxication following inhalation of butane gas from a canister in a 15 year-old boy. PMID- 8355325 TI - Massive oral ingestion of elemental mercury. AB - A 42 year old male, while repairing a sphygmomanometer, intentionally ingested an estimated 3 kg (220 mL) of metallic mercury. During admission, only tremor, irritability, forgetfulness and fatigue were noted. There were no obvious gastrointestinal or hepatic complications. Blood and urine mercury levels were significantly elevated. Most of the metallic mercury was cleared from the gut within 10 days. A few months later, hepatic dysfunction with jaundice developed. Serial investigations did not suggest a viral etiology or alcoholism. Liver function tests and blood and urine mercury levels returned to normal over the next 10 months. The observation suggests that massive and prolonged retention of metallic mercury may facilitate the conversion of metallic, elemental mercury to divalent mercury and its subsequent absorption with development of hepatic dysfunction. PMID- 8355326 TI - Non-traumatic rhabdomyolysis complicating antihistamine overdose. AB - Antihistamines are common over the counter medications which are frequently involved in overdoses. The usual clinical course is dominated by the anticholinergic affects of these agents; it includes significant autonomic and central nervous system effects and direct cardiac toxicity (1). We report a case of a suicide attempt in a young adult male where ingestion of the antihistamines diphenhydramine and doxylamine was complicated by non-traumatic rhabdomyolysis and acute renal failure. PMID- 8355327 TI - Organophosphate poisoning complicated by rhabdomyolysis. PMID- 8355328 TI - Urine butoxyacid acid as a therapeutic guide. PMID- 8355329 TI - Peripheral pulmonary lesions: ultrasonic features and ultrasonically guided fine needle aspiration biopsy. AB - When transthoracic biopsy is required for diagnosing lung diseases, radiographic procedures are the methods of choice, sonographic application being still limited. Sixty-four consecutive patients with pulmonary lesions adjacent to the chest wall underwent sonography. Findings showed hypoechoic homogeneous lesions (56 cases) with posterior regular margin (57 cases). Increasing echoes deep to the mass and sonographic interruption of hyperechoic surface were seen in all patients. In two cases, chest wall invasion had been diagnosed. Histologic diagnosis was made in 55 of the 64 patients (85.9%). Two pneumothoraces occurred. Sonography is a useful, accurate, and safe technique for diagnosing selected pulmonary lesions. PMID- 8355330 TI - New challenge for endorectal sonography: diagnosis of fecal incontinence. AB - The puborectalis muscle is a major determinant in the control of fecal continence. With endorectal sonography puborectalis function was assessed by determining puborectalis length in the resting (D1) and contracted (D2) states and calculating the percentage of shortening (D1-D2/D1)(100). The puborectalis length was defined as the shortest distance between the symphysis pubis and the rectal mucosa. The mean puborectalis length at rest did not differ in control subjects (29.5 +/- 1.0 mm) and incontinent patients (29.0 +/- 2.9 mm). With voluntary contraction a statistically significant difference (P < 0.001) was seen in the percentage of shortening between control subjects (15.4 +/- 1.1%) and incontinent patients (4.7 +/- 2.8%). Endorectal ultrasonography is a useful method to diagnose fecal incontinence. PMID- 8355331 TI - The fetal transverse cerebellar diameter/abdominal circumference ratio: a gestational age-independent method of assessing fetal size. AB - The relationship between the fetal TCD and the AC throughout pregnancy was investigated in a prospective, cross-sectional study of 700 well dated, normal pregnancies between 14 and 42 weeks of gestation and tested in 30 known SGA infants. Fetal measurements included the TCD, AC, BPD, HC, and FL. The TCD/AC ratio was calculated for each patient. Statistical analysis using linear regression and Student's t-test was performed. Strong correlation existed between gestational age and transcerebellar diameter (R2 = 0.9464), between gestational age and AC (R2 = 0.9685), and between TCD and AC (R2 = 0.9561). The TCD/AC ratio was normally distributed with a mean +/- SD of 13.69 +/- 0.94% (median, 13.71%). The 10th and 90th percentiles were 12.50% and 14.86%, respectively. The ratio remained constant throughout pregnancy with respect to gestational age (R2 = 0.0084). A TCD/AC ratio greater than the 90th percentile was present in 87% (26/30) known SGA infants. The TCD/AC ratio is a stable, gestational age independent parameter that may be useful in the early detection of fetal growth abnormalities. PMID- 8355332 TI - Pregnancy outcome after a first trimester sonogram demonstrating fetal cardiac activity. AB - We conducted a prospective study to assess pregnancy outcome after a first trimester sonogram demonstrating a singleton intrauterine gestation with fetal cardiac activity. In each of the 556 cases, data recorded included indication for the sonogram, results of the sonogram, and pregnancy outcome. Sonographic abnormalities were found more frequently in patients scanned because of symptoms (14.0%) than among patients scanned for routine indications (6.0%) (P < 0.05, chi squared). Among 556 patients with known outcomes, the overall loss rate was 9.4%. A trend was seen toward a higher loss rate in patients with abnormal than normal sonograms (15.2% versus 8.8%). The loss rate after a normal scan was similar in symptomatic (10.6%) and asymptomatic patients (9.1%) and declined progressively with gestational age from 17.0% at 6 to 7.9 weeks to 4.3% at 12 to 13 weeks (P < 0.01, chi-squared). These results can be used to convey prognostic information to patients after a normal first trimester sonogram demonstrating fetal cardiac activity. The likelihood of a good pregnancy outcome can be stated as a function of gestational age, and a symptomatic patient can be reassured after a normal scan that her prognosis is similar to that of an asymptomatic patient with a normal sonogram. PMID- 8355333 TI - Screening for ovarian cancer in women with breast cancer with transvaginal sonography and color flow imaging. AB - The aim of the present study was to determine the efficacy of transvaginal color flow imaging as a screening tool for ovarian cancer. Six hundred patients with previous breast carcinoma were screened for ovarian cancer. Screening was performed using transvaginal sonography with color flow imaging. Serum CA 125 levels were measured in patients with abnormal sonographic findings. Eighty-three percent of the ovaries were detected in the premenopausal patients by ultrasonographic scanning and only 26% of the ovaries were detected in the postmenopausal patients. Intraovarian blood vessels were detected in 11% of the premenopausal women. The PI was less than 1 in 80% of these ovaries, but, on repeated examinations, the values of PI increased in all the blood vessels to greater than 1. Intraovarian blood vessels were detected in 1.8% of the normal ovaries observed in the postmenopausal women, but PI was always greater than 1. Eleven women with complex ovarian cysts (not simple) and one woman with enlarged ovaries underwent explorative laparotomy. In three women, primary malignant ovarian tumors were diagnosed and in one woman metastatic ovarian cancer was diagnosed. The specificity of sonography in detecting malignant ovarian tumors was 97.5% and the positive predictive value was 25%. The specificity of color flow imaging in detecting primary malignant ovarian tumors was 99.8% and the positive predictive value was 60%. In selected groups of women, screening for ovarian cancer with transvaginal color flow imaging may be justified. PMID- 8355334 TI - Imaging of the vertebrobasilar system by transcranial color-coded real-time sonography. AB - The vertebrobasilar system was investigated in 75 persons by TCCS to evaluate the applicability and diagnostic capacity of this transcranial Duplex technique. Transforaminal and transtemporal acoustic windows were employed to identify the vertebral arteries, basilar artery (PCA) and major branches of the vertebrobasilar system. The frequency of identifying the basilar artery and the PCA ranged from 84 to 94% but was poor for the distal segment of the basilar artery (45.3%). The origin of the basilar artery was disclosed by transcranial Duplex sonography at an average depth of 7.0 cm (range 6.0 to 8.0 cm). The assignment of the obtained flow signals to specific vascular segments was improved by this new technique. In addition, four persons received a maximum of six intravenous injections of a transpulmonary stable sonographic contrast agent (SHU 508 A) to enhance Doppler signal intensity derived from the vertebrobasilar system. The vascular trunk and all major branches of the vertebrobasilar system were identified in these four persons. We conclude that TCCS of the vertebrobasilar system will improve reliability of transcranial sonographic examination. PMID- 8355335 TI - Traumatic central retinal artery occlusion: diagnosis by color Doppler imaging. PMID- 8355336 TI - Changing ultrasonographic appearance of a fetal ovarian cyst twisted in utero. PMID- 8355337 TI - Development and disappearance of anterior cerebral artery collateral flow detected by transcranial Doppler sonography in a stroke patient. PMID- 8355338 TI - Idiopathic hypertrophy of gastric folds in children. PMID- 8355339 TI - Prenatal ultrasonic diagnosis of retroperitoneal cystic lymphangioma. PMID- 8355340 TI - Epizootiology of canine distemper in New Jersey raccoons. AB - Seventeen epizootics of canine distemper (CD) involving at least 615 raccoons (Procyon lotor) were identified between 1 September 1977 and 25 March 1991 in New Jersey (USA). Epizootics occurred three times at four year intervals in three areas. Based on this cycling, the wide distribution of CD cases, and their occurrence between epizootics, I propose an enzootic status for CD in New Jersey raccoons. The peak period prevalence of raccoon canine distemper cases occurred at the end of the mating season in March. Another period of CD activity began with increased movements of the young in September. Epizootics were associated with river drainages and other wetlands. Age and sex distribution of raccoons with CD was not significantly different (P > 0.05) from that of an asymptomatic composite sample of four northern New Jersey raccoon populations. Lethargy was the most commonly reported clinical sign in raccoons with alert or aggressive behavior rarely observed. PMID- 8355341 TI - Rabies in African wild dogs (Lycaon pictus) in the Serengeti region, Tanzania. AB - Rabies was confirmed as the cause of death of one African wild dog (Lycaon pictus) in the Serengeti region, Tanzania. One adult African wild dog in the same pack showed central nervous signs consistent with rabies infection. Inactivated rabies vaccine was administered intramuscularly to African wild dogs in two packs, by dart or by hand following anesthesia. These individuals comprised all known adults in the Serengeti National Park. In a limited study of seroprevalence of rabies antibody carried out at the time of vaccination, 3 of 12 African wild dogs sampled in the Serengeti had rabies serum neutralizing antibody titers before vaccination. Paired serum samples from two individuals sampled after vaccination showed increased antibody titers. PMID- 8355342 TI - Prevalence of Brucella sp. antibodies in feral swine in Florida. AB - Serum samples collected from feral swine (Sus scrofa) throughout Florida (USA) from 1974 to 1989 were tested for antibodies to Brucella sp. by the card test, the standard tube test, the rivanol test or the complement fixation test. Seropositive swine were detected at six of 18 sites with a composite prevalence of 23.4% (238 of 1,015 samples; range = 5.5% to 33.3%) for sites with seropositive swine. At one site for which age and sex data were available there was no significant difference (P = 0.50) in seroprevalence between males and females. Antibody prevalence in adult (> or = 8 mo) and juvenile swine (< 8 mo), however, was significantly different (P < 0.05). Based on these data, Brucella sp. infections are limited only to certain populations of feral swine. To avoid the spread of Brucella sp. organisms, however, relocation of feral swine is not recommended. PMID- 8355343 TI - The groundhog tick Ixodes cookei (Acari: ixodidae): a poor potential vector of Lyme borreliosis. AB - Evidence for infection with the spirochete, Borrelia burgdorferi, was sought in Ixodes cookei and in groundhogs (Marmota monax) in southern Ontario, Canada, and ticks fed on experimentally inoculated hosts were examined for the spirochete. Borrelia burgdorferi was not detected by immunofluorescent examination of 110 larval, nymphal or adult I. cookei collected from the environment, or taken from humans and other animals. Three groundhogs inoculated with B. burgdorferi developed titers of 1:20 to 1:80 by the indirect immunofluorescent antibody test, but B. burgdorferi was not isolated from the spleens, kidneys, or urinary bladders of these animals. One of 30 wild groundhogs had an antibody titer of 1:20 to B. burgdorferi. Three (5%) of 59 I. cookei larvae fed on B. burgdorferi infected hamsters became infected, in comparison with 23 (28%) of 82 I. dammini larvae fed on the same hosts. Borrelia burgdorferi was present in 5%, 16% and 4% of molted I. cookei nymphs fed on infected hamsters, rats or a groundhog, respectively; prevalences of infection in I. dammini fed on the same hosts were significantly (P < 0.05) higher (45%, 36%, and 23%, respectively), as was the intensity of infection. A naive groundhog on which I. cookei nymphs from an infected cohort fed did not become infected with B. burgdorferi, but it is uncertain whether an infected tick engorged on the experimental host. Ixodes cookei seems to be an inefficient vector of B. burgdorferi, and is unlikely to be significant in nature. Groundhogs are potential wildlife reservoirs of B. burgdorferi, based on their capacity to transmit infection to I. dammini. PMID- 8355344 TI - Findings in pinnipeds stranded along the central and northern California coast, 1984-1990. AB - Personnel at The Marine Mammal Center (The Center) treated 1,446 stranded marine mammals recovered from the central and northern California (USA) coast from 1984 through 1990, including California sea lions (Zalophus californianus), northern elephant seals (Mirounga angustirostris), Pacific harbor seals (Phoca vitulina richardsi), northern fur seals (Callorhinus ursinus), Steller sea lions (Eumetopias jubatus), and Guadalupe fur seals (Arctocephalus townsendi). The primary disease findings in stranded California sea lions were renal disease, renal disease complicated by severe verminous pneumonia, verminous pneumonia, seizures of unknown etiology, and renal disease complicated by severe pneumonia of unknown etiology. Stranded elephant seals included pups, yearlings with dermatological problems, and neonates. Most harbor seals admitted to The Center were underweight and premature pups. Stranded northern fur seals included animals with seizures of unknown etiology and emaciated pups. Stranded Steller sea lions included underweight pups and aged adult females with pneumonia. Two Guadalupe fur seals had hemorrhagic gastroenteritis. Incidental findings at the time of stranding among the six species included verminous pneumonia and pneumonia of unknown etiology, renal disease, internal parasitism, ophthalmologic problems, gastrointestinal disorders, otitis externa, and external wounds. PMID- 8355345 TI - Experimental infection of domestic ducks and rodents by Notocotylus attenuatus (Trematoda: Notocotylidae). AB - In order to study transmission patterns of Notocotylus attenuatus five 3-wk-old domestic ducks, five 8-wk-old rats and ten 4-wk-old mice were infected with the parasite. All ducks became infected and all flukes were recovered from the intestinal ceca. Worms moved down the length of the cecum during development and as the parasites grew they changed their method of attachment. Flukes became gravid by day 16 post-infection, after which growth ceased. Egg filaments appear to play a role in the formation and movement of worm egg clusters from the distal portion of the cecum to the lumen of small intestine. Rodents also became infected with the parasite producing granulomatous nodular lesions in the lower small intestine but all flukes in the granulomata were dead. It is unlikely that transmission of this trematode can depend on mice and rats. PMID- 8355346 TI - Parasites of the arctic fox (Alopex lagopus) in Iceland. AB - Forty-four of 50 arctic foxes (Alopex lagopus) in Iceland harbored 15 species of intestinal parasites, including Protozoa: Eimeria sp. or Isospora sp. (in 4%); Trematoda: Cryptocotyle lingua (24%), Plagiorchis elegans (4%), Brachylaemus sp. (12%), Tristriata sp. (10%), and Spelotrema sp. (8%); Cestoda: Mesocestoides canislagopodis (72%), Schistocephalus solidus (2%), and Diphyllobothrium dendriticum (4%); Nematoda: Toxascaris leonina (50%), Toxocara canis (2%), Uncinaria stenocephala (4%), and eggs of the lung worm Capillaria aerophila (6%); and Acanthocephala: Polymorphus meyeri (8%) and Corynosoma hadweni (2%). Only four of the species previously had been recorded in Iceland. Eleven species are new records in Iceland and six appear to be new host records. Two additional nematodes, Stegophorus stercorarii and Syphacia sp., probably were ingested accidentally with the prey. Foxes from coastal habitats harbored 14 parasitic species while only five species were found in foxes from inland habitats. Arctic foxes from coastal habitats generally had higher helminth burdens and harbored more parasitic species per fox than foxes from inland habitats. PMID- 8355347 TI - Injuries and behavior of raccoons (Procyon lotor) captured in the Soft Catch and the EGG traps in simulated natural environments. AB - The behavior and injuries of raccoons held for 12 and 24 hr in the Soft Catch and the EGG traps were studied in simulated natural environments. Nine raccoons held for 12 hr in the Soft Catch received minor injuries. However, one of nine raccoons held for 24 hr in this trap mutilated itself. The EGG trap caused only minor injuries to nine raccoons held for 12 hr, and nine others held for 24 hr. Thus the EGG trap can be expected, at a 95% level of confidence, to hold > or = 70% of the raccoons on traplines for 24 hr without serious injury. Raccoons captured in the Soft Catch fought their surroundings more than the trap. Those captured in the EGG trap fought the trap more than their surroundings. During the 24-hr capture study, escape behavior was more intense during the first 12 hr of capture, during both day and night. PMID- 8355348 TI - Hematologic, serologic values, histopathologic and fecal evaluations of bison from Yellowstone Park. AB - Hematologic and blood chemistry parameters were measured in 149 free-ranging American bison (Bison bison) from Yellowstone National Park, Wyoming (USA). Additionally, histopathologic evaluations of lung, liver, spleen, kidney, and mesenteric and bronchial lymph nodes were made from ten animals. Forty-five fecal samples were screened for the presence of helminth ova. Leukopenia and markedly low blood urea nitrogen concentrations were the most notable differences observed from other bison populations. All tissues examined were essentially normal; there was evidence of moderate intestinal parasite burdens. PMID- 8355349 TI - Response of Canada geese to a turf application of diazinon AG500. AB - We investigated the effects of a turf application of the insecticide diazinon AG500 on Canada geese (Branta canadensis) on a golf course in coastal Washington (USA). On both 19 and 26 March 1987, 1 ha of turf on a golf course located in Birch Bay, Washington was treated with diazinon AG500 at a target application rate of 2.2 kg active ingredient per hectare (AI/ha). Treated areas were then irrigated with 6 mm water. Grass and water samples were collected from three different sites one day before and 1, 3, 7 and 14 days after each application. Diazinon residues > or = 20 ppm were found in golf course grasses for one week after each application. Diazinon residues in study area ponds and creeks were > or = 17 ppb. Samples from two irrigation puddles one day post-application had 1.00 and 0.20 ppm of diazinon, respectively. Numbers of geese present declined following diazinon application; however, no goose mortality was observed. Geese spent 422 and 538 min feeding on the treated areas after the first and second diazinon applications, respectively. One goose feeding in treated areas demonstrated signs of poisoning (lethargy, ataxia) for several hours. Two other geese feeding in the treated areas may have been slightly intoxicated. During carcass searches, three American wigeon (Anas americana) carcasses were found. Based on brain cholinesterase (ChE) levels and gastrointestinal (GI) tract residues of diazinon present, we concluded that these wigeon died from diazinon poisoning. Numerous songbirds (Passeriformes) also fed on the treated turf but no apparent response to the insecticide was observed. PMID- 8355350 TI - Phocine distemper in harbor seals (Phoca vitulina) from Long Island, New York. AB - The first occurrence of phocine distemper (PD) disease in harbor seals (Phoca vitulina) from the United States is reported. Two seals stranded on Long Island, New York (USA) in February 1992 with clinical signs of respiratory distress, fever, and depression. Pneumonia and diffuse pulmonary congestion were the most significant post mortem findings. On histologic examination one seal had a diffuse broncho-interstitial pneumonia with formation of syncytia. The principal lesion in the second animal was nonsuppurative meningoencephalitis. Using immunoperoxidase staining, PD viral antigen was found in the cytoplasm of bronchiolar epithelium and cerebral cortex neurons. With a differential virus neutralization test, there were higher titers against phocine distemper virus (PDV) than against canine distemper virus. Thus, PDV is the most likely agent responsible for the observed lesions. PMID- 8355351 TI - Further studies on the susceptibility of raccoons (Procyon lotor) to a rabies virus of skunk origin and comparative susceptibility of striped skunks (Mephitis mephitis). AB - Two raccoons (Procyon lotor) were inoculated in the masseter muscles with 10(5.9) mouse intracerebral lethal dose50 (MICD50) of a rabies virus isolated from a naturally infected Iowa (USA) striped skunk (Mephitis mephitis). Five striped skunks were inoculated with either 10(0.7) or 10(2.1) MICLD50 of the same isolate. All five skunks died within 35 days following inoculation. Both raccoons survived 273 days without adverse effects, and virus was not isolated from saliva samples taken at between 25 and 273 days following inoculation. PMID- 8355352 TI - Isolation of Borrelia burgdorferi from the blood of a bushy-tailed wood rat in California. AB - Borrelia burgdorferi was isolated from the blood of a bushy-tailed wood rat (Neotoma cinerea) from northeastern California, USA. This is the first isolation of live B. burgdorferi spirochetes from a wild animal in California. Spirochetes were observed in stained tissues from the brain, liver, spleen, and kidneys. PMID- 8355353 TI - Serological evidence of Coxiella burnetii infection in wild animals in Japan. AB - One hundred and thirty-four (26%) of 511 sera from 11 wild animal species in eight prefectures in Japan had antibody titers to Coxiella burnetii by the enzyme linked immunosorbent assay. High prevalences were observed in Japanese black bears (Ursus thibetanus) (78%), Hokkaido deer (Cervus nippon yesoensis) (69%), Japanese hares (Lepus brachyurus) (63%), Japanese deer (Cervus nippon centralis) (56%), and to some extent in Japanese monkeys (Macaca fuscata) (28%). A low prevalence (13%) was observed in nutrias (Myocastor coypus). Japanese serows (Capricornis crispus), wild rats (Muroides sp.), raccoon dogs (Nyctereutes procyonoides viverrinus), wild pigs (Sus scrofa leucomystax), and masked palm civets (Paguma larvata) had no detectable antibodies to C. burnetii. Thus, six of 11 wild animal species in Japan were exposed to C. burnetii. Based on the high prevalences in some species, they may be a potential source of infection to both domestic animal and human populations. PMID- 8355354 TI - Mucor amphibiorum infection in platypus (Ornithorhynchus anatinus) from Tasmania. AB - Mucor amphibiorum, a fungus previously isolated from frogs and toads, is reported from free-living platypus, Ornithorhynchus anatinus, from rivers in northern Tasmania. This fungus is responsible for the severe ulcerative skin condition originally described by Munday and Peel (1983). Mucor amphibiorum was isolated from dermal lesions on four separate occasions. The gross and histopathological appearance of the fungal lesions were similar to the earlier description. In vivo this fungus develops as spherical forms containing a number of daughter spherules; no mycelia are seen in tissue sections. By contrast, the in vitro growth consists of aerial aseptate mycelia and sporangia, features typical of the genus Mucor. This is the first report of this organism causing a fatal disease in a mammal. Susceptibility to infection may be due to the platypus having a body temperature of 32 C while the maximum temperature for growth of M. amphibiorum is 36 C. PMID- 8355355 TI - Lobo's disease in a bottlenose dolphin (Tursiops truncatus) from Matagorda Bay, Texas. AB - Lobo's disease was diagnosed in a free-ranging male bottlenose dolphin Tursiops truncatus examined as part of a live-capture and release program conducted in Matagorda Bay, Texas, USA, during July 1992. Diagnosis was based on typical presentation of a raised skin lesion, with sub-epidermal granuloma and demonstration of typical features of the organism by light microscopy, using hematoxylin and eosin, and methenamine silver stains. This is the first instance of Lobo's disease found in a dolphin on the western coast of the Gulf of Mexico. PMID- 8355356 TI - Epizootic mortality of free-living green turtles, Chelonia mydas, due to coccidiosis. AB - At least 70 wild green sea turtles, Chelonia mydas, died in the Moreton Bay area of southeast Queensland, Australia over 6 wk in spring 1991. Based on the necropsy of 24 turtles, there was a severe enteritis or encephalitis associated with Caryospora cheloniae, a coccidial pathogen previously recorded only in farm reared Ch. mydas hatchlings. Infection was characterized by the presence of coccidia in extra-intestinal lesions. Oocysts were observed to sporulate, after which sporozoites escaped into seawater to form a novel stellate configuration. We conclude that C. cheloniae is pathogenic for life stages other than hatchling Ch. mydas and that naturally-occurring coccidiosis is a significant disease of free-living Ch. mydas. PMID- 8355357 TI - Enteric coccidia (Apicomplexa) in the small intestine of the northern spotted owl (Strix occidentalis caurina). AB - Sporulated oocysts (mean dimensions = 13.0 x 10.8 microns) and sporocysts (11.3 x 5.5 microns) of a coccidian resembling Frenkelia sp. or Sarcocystis sp. were present in the lamina propria of the small intestine of a naturally-infected northern spotted owl (Strix occidentalis caurina) collected near Medford, Oregon (USA). Dimensions of these oocytes and sporocysts appear to be considerably smaller than those from other sarcocystid species with avian definitive hosts. Additionally, numerous developmental stages and unsporulated oocysts (mean dimensions 22.8 x 17.8 microns) of a possible species of Isospora also were observed in the intestinal epithelium. This constitutes the first report of enteric coccidia from spotted owls. Neither parasite appeared to cause the death of the bird. PMID- 8355358 TI - Evaluation of fox-chasing enclosures as sites of potential introduction and establishment of Echinococcus multilocularis. AB - Following detection of Echinococcus multilocularis in red foxes (Vulpes vulpes) illegally imported into South Carolina (USA) for release in fox-chasing enclosures, a survey for E. multilocularis was conducted in four enclosures in Georgia (USA) and six enclosures in South Carolina. Survey methods included examination of potential small mammal intermediate hosts (n = 390) for E. multilocularis larvae, examination of fox and coyote (Canis latrans) scats (n = 59) for taeniid eggs, and examination of one possible canine definitive hosts for adult E. multilocularis. All intermediate and definitive hosts examined were negative for E. multilocularis and taeniid eggs were not recovered from fox and coyote fecal samples. Thus, E. multilocularis may not yet be established in fox chasing enclosures in Georgia and South Carolina. Despite the failure to demonstrate E. multilocularis in the fox-chasing enclosures surveyed, translocation of wild canids from known enzootic regions should be discouraged because E. multilocularis is known to be ecologically adaptable and because contact with potentially infected definitive hosts during translocation is a public health risk. PMID- 8355360 TI - The lungworm, Halocercus spp. (Nematoda: Pseudaliidae) in cetaceans from California. AB - Three cetaceans from Monterey Bay, California (USA), were infected with lung nematodes. A beaked whale calf, Mesoplodon sp. was infected with adult Halocercus sp. This represents a new host record for this nematode. The lungs of a northern right whale dolphin calf, Lissodelphis borealis, contained an unidentified nematode similar in size to Halocercus sp. The presence of Phyllobothrium delphini-type cestode larvae in its blubber is evidence that the calf was feeding on invertebrates. A pregnant harbor porpoise, Phocoena phocoena was infected with the lung nematode H. invaginatus, but the fetus was uninfected. We found no direct evidence of a transplacental mode of transmission for Halocercus sp. PMID- 8355359 TI - Parasitic meningoencephalitis in nurse sharks (Ginglymostoma cirratum). AB - Based on microscopic examination of the brains of seven wild-caught nurse sharks (Ginglymostoma cirratum), we observed a severe meningoencephalitis associated with numerous parasitic granulomas. The parasites were larval nematodes with morphological characteristics of the Superfamily Dracunculoidea. Although meningeal larval aggregates were associated with chronic inflammation, additional parasitic nodules found on the endocardial surface and perimandibular region did not provoke an inflammatory response. Neither the route of infection nor life cycle were determined. PMID- 8355361 TI - Spiroxys contorta (Nematoda: spirurida) in gastric granulomas of Apalone spinifera pallida (Reptilia: testudines). AB - Non-caseating granulomas containing larval spirurid nematodes (Spiroxys contorta) were observed in the gastric submucosa and muscularis externa of two pallid spiny softshells (Apalone spinifera pallida) from northcentral Texas (USA). In early granulomas, nematodes were not surrounded by a fibrous capsule but in older, mature granulomas, a fibrous capsule was present. Granulomas without nematodes also were present. PMID- 8355362 TI - Spiculopteragia spiculoptera and S. asymmetrica (Nematoda: Trichostrongyloidea) from red deer (Cervus elaphus) in Texas. AB - Specimens of Spiculopteragia spiculoptera and S. asymmetrica were recovered from the abomasa of five of ten naturally infected red deer (Cervus elaphus) in Texas (USA). Female specimens of Spiculopteragia were present in all five animals. Male specimens of S. spiculoptera and S. asymmetrica were present in one of five and three of five red deer, respectively. Spiculopteragia spiculoptera has not previously been recognized in the United States and the present report constitutes the first records of Spiculopteragia spp. in red deer from North America. It is likely that species of Spiculopteragia have been introduced to North America with the import of exotic cervids on several occasions. Focal populations of these nematodes have been established in North America; however, distribution of the parasites likely coincides with areas of residence of introduced populations of red deer and fallow deer (Cervus dama) in the Nearctic. PMID- 8355363 TI - Longistrongylus curvispiculum (Nematoda: Trichostrongyloidea) in free-ranging exotic antelope in Texas. AB - Longistrongylus curvispiculum was recovered from free ranging sable (Hippotragus niger), addax (Addax nasomaculatus) and biesa oryx (Oryx beisa) on two ranches in central Texas (USA). These nematodes represented a small portion of the total abomasal worm burden dominated by Haemonchus contortus. Female L. curvispiculum easily could be confused with other ostertaginae, but the spicules of the males were diagnostic. PMID- 8355365 TI - Direct consumer advertising of prescription drugs. PMID- 8355364 TI - Hepatic capillariasis in muskrats (Ondatra zibethicus). AB - We present the first prevalence data of hepatic capillariasis in muskrats in Pennsylvania and Connecticut (USA). The prevalence of hepatic capillariasis in five groups of muskrats coming from different locations and numbering 81, 229, 11, 19, and 20 animals, was 42%, 78%, 36%, 16%, and 0%, respectively. Liver lesions varied from minimal to severe multifocal granulomatous hepatitis, often containing adult worms or eggs. PMID- 8355367 TI - National Medical Association unveils billboard campaign to promote health in black communities. PMID- 8355366 TI - A piece of my mind. The legacy. PMID- 8355368 TI - New telecommunications relay services, other communication advances, will aid disabled people. PMID- 8355369 TI - From the National Institutes of Health. PMID- 8355370 TI - From the Centers for Disease Control and Prevention. Emergency department response to domestic violence--California, 1992. PMID- 8355371 TI - From the Centers for Disease Control and Prevention. Update: hantavirus disease- United States, 1993. PMID- 8355372 TI - 'Windows of opportunity' to address patients' concerns: too small and too few? PMID- 8355373 TI - 'Windows of opportunity' to address patients' concerns: too small and too few? PMID- 8355374 TI - 'Windows of opportunity' to address patients' concerns: too small and too few? PMID- 8355376 TI - Pressure ulcer prevention with low-air-loss beds. PMID- 8355375 TI - Survival after ovarian cancer treatment. PMID- 8355377 TI - Beauty parlor stroke: when a beautician becomes a physician. PMID- 8355378 TI - Giving pediatric immunizations the priority they deserve. PMID- 8355379 TI - Giving pediatric immunizations the priority they deserve. PMID- 8355380 TI - Giving pediatric immunizations the priority they deserve. PMID- 8355381 TI - Giving pediatric immunizations the priority they deserve. PMID- 8355382 TI - Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure. AB - OBJECTIVE: To investigate the importance of splanchnic ischemia in patients with acute circulatory failure by comparing gastric intramucosal pH as measured by tonometry with conventional methods of assessing adequacy of tissue oxygenation. DESIGN: Prospective cohort of patients with acute circulatory failure in first 24 hours after admission to the intensive care unit. SETTING: Two general intensive care units in London, England. PATIENTS: Consecutive sample of 83 patients of varying diagnostic categories that required pulmonary artery catheterization. MAIN OUTCOME MEASURES: Gastric intramucosal pH and hemodynamic, oxygen transport, and metabolic variables were measured on admission and at 12 hours and 24 hours after admission. Prediction of outcome (death or survival) by each measurement was assessed by sensitivity, specificity, and logistic regression analysis. RESULTS: Mean 24-hour Acute Physiology and Chronic Health Evaluation (APACHE II) score was 20.3. There were significant differences in mean gastric intramucosal pH between survivors and nonsurvivors on admission and at 24 hours, (7.40 vs 7.28, 7.40 vs 7.24, respectively; P < .001). Admission heart rate was higher (116 vs 101 beats per minute; P < .003) and mean arterial pressure lower (82 vs 97 mm Hg; P < .01) in nonsurvivors. There were no consistent differences in cardiac index, oxygen delivery, and oxygen uptake between survivors and nonsurvivors. Admission arterial pH was significantly lower (7.3 vs 7.36; P < .003), base excess more negative (-5.3 vs -1.9; P < .001), and lactate concentration higher (3.14 vs 1.91 mmol/L; P < .03) in nonsurvivors. Gastric intramucosal pH had a sensitivity of 88% for predicting death and a likelihood ratio of 2.32, higher than for any other variable. Only gastric intramucosal pH at 24 hours independently predicted outcome. CONCLUSIONS: Gastric intramucosal pH was the most reliable indicator of adequacy of tissue oxygenation in this group of patients. Inadequate regional blood flow as detected by a reduction in gastric intramucosal pH, but not by systemic measures, is an important contributor to morbidity and mortality in intensive care units. PMID- 8355383 TI - Prehospital-initiated vs hospital-initiated thrombolytic therapy. The Myocardial Infarction Triage and Intervention Trial. AB - OBJECTIVE: To determine the effect of prehospital-initiated vs hospital-initiated treatment of myocardial infarction on clinical outcome. DESIGN: Randomized, controlled clinical trial. SETTING: Multicenter study involving 19 hospitals and all paramedic systems in the Seattle, Wash, metropolitan area. PATIENTS: A total of 360 patients with symptoms for 6 hours or less, no risk factors for serious bleeding, and ST-segment elevation were selected by paramedics and a remote physician for inclusion into the trial. They represented 4% of patients with chest pain who were screened and 21% of those with acute infarction. INTERVENTIONS: Patients were allocated to have aspirin and alteplase treatment initiated before or after hospital arrival. Intravenous sodium heparin was administered to both groups in the hospital. MAIN OUTCOME MEASURE: The primary endpoint was a ranked composite score (combining death, stroke, serious bleeding, and infarct size). The relation between time to treatment and outcome (composite score, infarct size, ejection fraction, and mortality) was also assessed. RESULTS: Initiating treatment before hospital arrival decreased the interval from symptom onset to treatment from 110 to 77 minutes (P < .001). Although more patients whose therapy was initiated before hospital arrival had resolution of pain by admission (23% vs 7%; P < .001), there were no significant differences in the composite score (P = .64), mortality (5.7% vs 8.1%), ejection fraction (53% vs 54%), or infarct size (6.1% vs 6.5%). A secondary analysis of time to treatment and outcome showed that treatment initiated within 70 minutes of symptom onset was associated with better outcome (composite score, P = .009; mortality, 1.2% vs 8.7%, P = .04; infarct size, 4.9% vs 11.2%, P < .001; and ejection fraction, 53% vs 49%, P = .03) than later treatment. Identification of patients eligible for thrombolysis by paramedics reduced the hospital treatment time from 60 minutes (for patients not in the study) to 20 minutes (for study patients allocated to begin treatment in the hospital). CONCLUSION: There was no improvement in outcome associated with initiating treatment before hospital arrival; however, treatment within 70 minutes of symptom onset--whether in the hospital or in the field--minimized the infarct process and its complications. PMID- 8355384 TI - Anabolic-androgenic steroid use in the United States. AB - OBJECTIVE: To estimate the size of the anabolic-androgenic steroid (AAS) user population in the United States, to examine characteristics of AAS users, and to explore the association between AAS use and the use of other illicit drugs as well as self-reported aggressive behaviors. DESIGN: A cross-sectional study using data from the 1991 National Household Survey on Drug Abuse. STUDY POPULATION: The survey covered the population aged 12 years and older living in households in the United States. The results of the survey were based on personal interviews combined with self-administered questionnaires from 32,594 respondents. These respondents were randomly selected by means of a stratified multistage area sample of the household population. RESULTS: Estimates based on data from the National Household Survey on Drug Abuse indicated that there are more than 1 million current or former AAS users in this country, with more than half of the lifetime user population being 26 years of age or older. More than 300,000 individuals used AAS in the past year. Males had higher levels of AAS use during their lifetime than females (0.9% and 0.1%, respectively; P < .01). The median age of first use of AAS for the study population was 18 years; for 12- to 17-year olds, the median age of initiation was 15 years. Among 12- to 34-year-olds, AAS use was significantly and positively associated with the use of other illicit drugs (P < .05), cigarettes (12- to 17-year-olds only; P < .01), and alcohol (P < .01). Furthermore, AAS use is highly correlated with self-reported aggressive behavior (P < .01) and crimes against property (P < .01). CONCLUSIONS: These results indicate that AAS use impacts a large number of men and women from various racial and age groups across the nation. While causal inferences cannot be made regarding the associations between AAS use and use of other drugs as well as antisocial behavior, these findings should enhance our ability to profile the typical AAS user. PMID- 8355385 TI - Alcohol-related hospitalizations of elderly people. Prevalence and geographic variation in the United States. AB - OBJECTIVE: To determine the prevalence, geographic variation, and charges to Medicare of alcohol-related hospitalizations among elderly people in the United States. DESIGN: A cross-sectional prevalence study using 1989 hospital claims data from the Health Care Financing Administration (HCFA). Rates were determined using (1) hospital claims records from the HCFA's Medicare Provider Analysis and Review Record (MEDPAR) database for all Medicare Part A beneficiaries aged 65 years and older; (2) county population estimates for 1985 from the Bureau of the Census; and (3) per capita consumption of alcohol by state in 1989 as estimated by the US Department of Health and Human Services. SETTING: Data include all hospital inpatient Medicare Part A beneficiaries aged 65 years and older in the United States in 1989. RESULTS: The prevalence of alcohol-related hospitalizations among people aged 65 years and older nationally in 1989 was 54.7 per 10,000 population for men and 14.8 per 10,000 for women. Comparison with hospital records showed that MEDPAR data had a sensitivity of 77% to detect alcohol-related hospitalizations. There was considerable geographic variation; prevalence ranged from 18.9 per 10,000 in Arkansas to 77.0 per 10,000 in Alaska. A strong correlation existed between alcohol-related hospitalizations and per capita consumption of alcohol by state (Spearman correlation coefficient, .64; P < .0001). In 1989, the hospital-associated charges to Medicare for all admissions where the primary diagnosis was alcohol related (N = 33,039) totaled $233,543,500. Median charge per hospital stay was $4514. CONCLUSIONS: Alcohol related hospitalizations among elderly people are common; rates were similar to those for myocardial infarction as detected by the same method. The charges to Medicare for this preventable problem are considerable. Ecological analysis suggests that per capita consumption in the total US population predicts alcohol related hospitalizations in the elderly population. PMID- 8355386 TI - Fee-for-time system. A conceptual framework for an incentive-neutral method of physician payment. PMID- 8355387 TI - Endometrial ablation complicated by fatal hyponatremic encephalopathy. AB - OBJECTIVES: To investigate the occurrence of hyponatremic encephalopathy and the effects of therapy for symptomatic hyponatremia on outcome in women undergoing endometrial ablation. DESIGN AND SETTING: Consultations from university affiliated and community hospitals from June 1991 to June 1992. PATIENTS: Four generally healthy women who underwent elective endometrial ablation for dysfunctional bleeding and developed hyponatremic encephalopathy. INTERVENTIONS: Three patients were promptly treated with hypertonic (514 mmol/L) sodium chloride such that the serum sodium level increased from 102 to 123 mmol/L within 24 hours. The fourth patient was not treated until after suffering grand mal seizures followed by respiratory arrest. MAIN OUTCOME MEASURES: Of the four patients who developed hyponatremic encephalopathy, the diagnosis was established before respiratory arrest occurred in three. The operative procedure was terminated and all three were aggressively treated with intravenous hypertonic sodium chloride, which raised the serum sodium level to modestly hyponatremic levels (120 to 130 mmol/L). All three completely recovered without sequelae. The fourth patient suffered respiratory arrest before therapy could be initiated. The patient remained comatose, and central diabetes mellitus and insipidus developed. She never regained consciousness and died after several days. Autopsy revealed cerebral edema and tonsillar herniation. RESULTS: The mean (+/- SD) preoperative serum sodium level was 138 +/- 1 mmol/L; at the time of diagnosis of hyponatremia, it was 107 +/- 13 mmol/L. In two patients, hyponatremic encephalopathy was diagnosed intraoperatively because of tremulousness and either hypothermia or hypoxemia. In the other two patients, the diagnosis was made postoperatively because of headache, nausea, emesis, and in one of these patients, respiratory arrest. CONCLUSIONS: Women undergoing elective endometrial ablation can develop severe symptomatic hyponatremia, which can be fatal. The presence of symptoms suggesting hypo-osmolality should lead to immediate measurement of plasma sodium level. If hyponatremia with hypo-osmolality is present, early and appropriate therapy for the hyponatremia should be instituted before respiratory insufficiency occurs. PMID- 8355388 TI - The clinical evaluation of new drugs for sepsis. A prospective study design based on survival analysis. AB - OBJECTIVE: To develop a survival model and severity assessment method to estimate the 28-day mortality risk for patients with sepsis syndrome entering phase 2 and 3 drug evaluations. DESIGN: Retrospective analysis of intensive care unit admissions with sepsis syndrome by means of log-normal regression to identify risk factors for 28-day mortality. Prospective application of the model to patients with gram-negative infection meeting sepsis syndrome criteria from separate data collection (validation group). PATIENTS: A total of 58,737 intensive care unit admissions at 107 hospitals in the United States and Western Europe screened to yield 1195 patients meeting entry criteria for the sepsis syndrome study for the original model; 295 hospitalized patients with gram negative infection meeting criteria for sepsis syndrome for validation. MAIN OUTCOME MEASURES: Survival time and mortality at 28 days after fulfillment of the sepsis syndrome criteria. RESULTS: Acute physiologic abnormalities were the most important prognostic factors influencing outcome (82% of total chi 2). Specific disease resulting in intensive care unit admission and the time the patient was in the hospital and intensive care unit before qualification were also independent risks, as were age and a clinical history of cirrhosis. The model's overall classification accuracy was a Somers' Dyx of .52 (rank correlation between predicted risk and 28-day mortality) (receiver operating characteristic area, 0.76), with equal accuracy (Dyx = .59; receiver operating characteristic area, 0.80) in the independent group of patients. CONCLUSIONS: We created an accurate independent estimate for 28-day mortality risk for patients with sepsis syndrome (severe sepsis). This estimate could improve the evaluation of new drugs by investigating whether the drug's benefit varies by patient risk and then determining the amount of benefit for individual patients. PMID- 8355389 TI - Does this patient have sinusitis? Diagnosing acute sinusitis by history and physical examination. PMID- 8355390 TI - The gastrointestinal tract. The canary of the body? PMID- 8355391 TI - House of Delegates reaffirms editorial independence for AMA's scientific journals. PMID- 8355392 TI - Morphological study on vagal innervation in human atrioventricular valves using histochemical method. AB - To demonstrate innervation in human atrioventricular valves, we examined the tricuspid and mitral valves of apparently normal autopsied hearts of four men (ages ranging from 50 to 74 years). Whole valve tissues were stained for acetylcholinesterase by a histochemical method. Acetylcholinesterase-positive nerve fibers with a diameter of 2 to 5 microns were distributed widely in the deep atrialis of the atrioventricular valves and partly in the fibrosa. The nerve fibers formed a network or plexus from the base to the anatomical edge of the valves. Meshes of the nerve fiber network were more dense towards the base and at the commissure than either towards the edge or at the body. Thicker nerve fibers, which were interspersed coarsely in the leaflets, were intercalated by special varicose apparatuses at a few sites in their long running course. On the contrary, thinner nerve fibers which were distributed abundantly, ended, as a rule, in small dotor brush-like formations. Approximately half of the chordae tendineae were innervated by the nerve fibers. The mode of vagal innervation suggests that the nerve system may assist valve movement by moderating myocyte contraction in the valve base and change valve structure by sensing a stress in the valves. PMID- 8355393 TI - Age-related changes of sinus node function and autonomic regulation in subjects without sinus node disease--assessment by pharmacologic autonomic blockade. AB - To assess the relationship between aging and autonomic regulation of sinus node function, 56 subjects of various ages (range 14-75 years, mean 43 +/- 19 years) without sinus node disease were studied. Heart rate, corrected sinus node recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) pharmacologic autonomic blockade (propranolol + atropine i.v.). Percent chronotropies of the above parameters were calculated by a modified Jordan's method. Basic heart rate and basic corrected sinus node recovery time did not vary with age (r = -0.15, r = 0.08, respectively), while basic sinoatrial conduction time tended to increase with age (r = 0.32, p < 0.05). Intrinsic heart rate decreased (r = -0.76, p < 0.001), and intrinsic corrected sinus node recovery time and intrinsic sinoatrial conduction time both increased with age (r = 0.55, p < 0.001; r = 0.56, p < 0.001, respectively). The younger the subject, the more negative the percent chronotropies of the above parameters were, and the percent chronotropies correlated positively with age (r = 0.68, p < 0.001; r = 0.52, p < 0.001 and r = 0.34, p < 0.05, respectively). In conclusion, intrinsic sinus node functions deteriorated with age. Furthermore, parasympathetic tone on the sinus node functions decreased with age, which may compensate for age-related deterioration of intrinsic sinus node function. PMID- 8355394 TI - Determinants of beneficial effect of heparin exercise treatment on treadmill capacity and long-term efficacy of the therapy in patients with chronic effort angina. AB - The purpose of the present study was to evaluate the factors which influence the effect of heparin exercise treatment on treadmill capacity, and to examine the long-term efficacy of the treatment in 16 patients with chronic effort angina. Treadmill exercise was performed 20 times for 2 to 3 weeks according to standard Bruce protocol. A single intravenous dose of heparin (5,000 IU) was given 10 min before each exercise period. Exercise with heparin pretreatment increased the total exercise duration from 6.6 +/- 1.6 (SD) to 9.4 +/- 1.9 min (p < 0.05) and the maximal rate-pressure product from 19,200 +/- 4,700 to 24,700 +/- 5,900 mmHg.beats/min (p < 0.05). The rate-pressure product at the onset of angina was also increased by 32% (p < 0.05). The ST segment depression at the same exercise time as in control exercise was ameliorated from 0.16 +/- 0.05 to 0.12 +/- 0.06 mV (p < 0.05). Multivariate analysis of the determinants of the effect of the treatment on treadmill capacity indicated that the treatment is more effective in patients without previous myocardial infarction. All of the above-mentioned variables of treadmill capacity did not change significantly during a follow-up period of 13 +/- 7 months (range; 4-24 months). These findings lend further support to heparin exercise treatment as a possible therapeutic approach in patients with chronic stable effort angina, and particularly in those without previous infarction. PMID- 8355395 TI - Augmentation of smoking cessation education by urinary cotinine measurement. AB - Monitoring the current smoking status by an objective method may augment the effects of smoking cessation instruction. To quantitatively evaluate smoking status and its modification by smoking cessation instruction, urinary cotinine, a major metabolite of nicotine, was measured by radioimmunoassay in 64 patients with a smoking habit before and during smoking cessation instruction. Urinary cotinine levels were used to discriminate between smokers and nonsmokers (with 50 ng/ml used as a threshold). In 49 patients who claimed to have stopped smoking, urinary cotinine concentrations 1 month after instruction indicated that only 30 (61%) of them had actually stopped (before: 243 +/- 104, after: 1 +/- 3 ng/ml) (mean +/- standard deviation). In the remaining 15 patients who failed to stop smoking while reporting a reduction of cigarette consumption (before: 27 +/- 12, after: 7 +/- 5/day), there was no appreciable reduction in urinary cotinine levels (before: 298 +/- 140, after: 229 +/- 171 ng/ml). When the patients who had failed to stop smoking again received intensive smoking cessation instruction, the success rate increased from 47% (30/64) to 69% (44/64) (p < 0.05). Thus, urinary cotinine measurement may provide a useful and quantitative method for monitoring actual smoking habits and thus augment the efficacy of smoking cessation educational programs. PMID- 8355396 TI - The relationship between serum lipoprotein(a) and restenosis after initial elective percutaneous transluminal coronary angioplasty. AB - The purpose of this study was to elucidate the possible link between lipoprotein(a) (Lp(a)) and the occurrence of restenosis after initial elective percutaneous transluminal coronary angioplasty (PTCA). Serum lipids, including Lp(a), total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B), and the Apo B/Apo A-I ratio were examined in 63 consecutive patients (41 men and 22 women, average age 63 +/- 8 years) who underwent initial elective PTCA in our department. Forty two target lesions were in left anterior descending, 10 were in left circumflex and 11 were in right coronary branches. Restenosis was observed in 22 patients (35%) 6.4 +/- 2.6 months after PTCA. The serum Lp(a) level was significantly higher in the restenosis group than in the non-restenosis group (38.0 vs 19.9 mg/dl, p < 0.05). A significant correlation was observed between serum Lp(a) levels and the degree of % restenosis after PTCA (r = 0.557, p < 0.001). However, other lipids showed no significant relationship to restenosis. In addition, the % stenosis before PTCA was found to be related to the occurrence of restenosis after successful PTCA. We conclude that the serum Lp(a) level has a close correlation with the degree of % restenosis after PTCA, and may be a useful index for predicting the possibility of restenosis after PTCA, especially in patients with an Lp(a) level above 30 mg/dl. PMID- 8355397 TI - Functional limitation of recruitable collaterals in human subjects--ST segment deviation on intracoronary electrocardiogram during transient coronary occlusion induced by balloon inflation. AB - Three patients showed ST elevation on precordial electrocardiogram and ST depression on intracoronary electrocardiogram during angioplasty of the left anterior descending coronary arteries (LAD). While none of the patients had spontaneously visible collaterals, all showed transient recruitable collaterals to the LAD. No evident collaterals into the diagonal branches were observed. Possibly, if the intracoronary electrocardiogram represents the potential changes of the epicardial surface in the vicinity of the guidewire tip, then endocardial ischemia may have developed even though epicardial ischemia was not observed, due to relatively sufficient blood flow through the recruitable collaterals to the LAD. ST elevation on the precordial electrocardiogram may have represented epicardial and endocardial ischemia of the diagonal branches, where the recruitable collaterals could not protect against transmural ischemia. These phenomena suggests that the recruitable collaterals are functionally limited during acute coronary occlusion, even though the collaterals are well developed. PMID- 8355398 TI - Influence of right ventricular ischemia on precordial ST depression during right coronary artery occlusion. AB - To determine the cause of precordial ST depression in acute inferior myocardial infarction, we evaluated the relationship between precordial ST deviation and ventricular involvement. Forty-nine patients who were admitted to the hospital with an acute inferior myocardial infarction, and 60 patients who were treated with elective angioplasty to the right coronary artery, were analyzed. All patients had single vessel disease and were divided into 2 groups (A and B) according to the site of the lesion. Patients in group A had a lesion proximal to the largest right ventricular branch, while in group B the lesion was distal to that branch. There were no differences in inferior ST elevation between the 2 groups, but precordial ST segments were more depressed in group B than in group A. A significant correlation was observed between inferior and precordial ST deviation in group B, but not in group A. These results were similar in patients with myocardial infarction and in those treated by angioplasty. These results suggest that precordial ST depression in an evolving inferior infarction is due to reciprocal ST deviation which reflects inferoposterior involvement. In addition, when inferior infarction is accompanied by right ventricular involvement the precordial ST depression is lessened. PMID- 8355399 TI - Evaluation of the effectiveness of 5'-nucleotidase inhibitor and allopurinol in myocardial ischemia. AB - The effect of 5'-nucleotidase inhibitor (AMP-C) and xanthine oxidase inhibitor (Allopurinol: ALLO) on myocardial functional recovery and the restoration of myocardial high energy phosphates after 15 min of normothermic global ischemic insult, was studied in the isolated isovolemic Langendorff rat heart model. Fifty nine rats were divided into 4 groups: Group I; saline, Group II; AMP-C plus ALLO, Group III; AMP-C, Group IV; ALLO. Intermittent infusion of drugs was delivered in 3 ml of solution at 5 min intervals during ischemia. Percent recovery of left ventricular systolic function was as follows: Group I; 74.2 +/- 3.6%, Group II; 87.7 +/- 1.7%, Group III; 83.5 +/- 3.1%, Group IV; 86.4 +/- 2.6%. Improved recovery was statistically significant only in Group II (p < 0.05 vs Group I). Suppression of reactive hyperemia was seen with reperfusion in the groups which had been treated with AMP-C (i.e., Groups II and III). Myocardial adenine nucleotides and purines were measured in 6 hearts in each group using high performance liquid chromatography. Myocardial ATP levels was 0.89 +/- 0.16 nmol/mg left ventricular wet weight in Group I, 1.37 +/- 0.12 in Group II (p < 0.05 vs Group I), 1.42 +/- 0.17 in Group III (p < 0.05) and 1.17 +/- 0.15 in Group IV. This study demonstrates that intermittent infusion of AMP-C plus ALLO during global myocardial ischemia results in improved myocardial functional recovery and improved preservation of high energy phosphates. PMID- 8355400 TI - Efficacy of carbon monoxide laser in selectively intimal thermal welding- implications for laser balloon angioplasty. AB - Excessive vascular damage causes excessive vascular repair, which results in restenosis. To limit the thickness of the coagulation layer in laser balloon angioplasty, we used a carbon monoxide (CO) laser, which has high tissue absorption, as a therapy laser source instead of a Nd: YAG laser. To investigate the benefit of short-penetration CO laser light to vascular tissue, excised human abdominal aorta was irradiated with a CO laser through a 30 microns polyethylene membrane. The temperature of the vascular tissue was continuously monitored during irradiation. CO laser irradiation of 20 W/cm2 was performed in either a continuous mode or an intermittent mode with various duty ratios (exposure/interval duration). With a total fluence of 200 J/cm2, the adventitial temperature decreased as the duty ratio was reduced. The adventitial temperature at a duty ratio of 1:2 was 43 degrees C. Microscopic examination of aorta which had been intermittently irradiated duty ratio of 1:2 showed thermal coagulation localized within the intima and a flattened intimal surface. These results suggest that intermittent laser irradiation with a CO laser can be used to limit the depth of thermal coagulation, and can selectively weld the intima without excessive thermal damage. Laser balloon angioplasty using a CO laser may help to prevent restenosis. PMID- 8355401 TI - Use of biplane transesophageal echocardiographic guide in radiofrequency catheter ablation of Wolff-Parkinson-White syndrome with left side Kent bundle. AB - We report 2 patients with Wolff-parkinson-White Syndrome, who underwent radiofrequency (RF) catheter ablation under observation by biplane transesophageal echocardiography. One of the patients had Kent bundle in the lateral wall of the left ventricle, and the tip of the catheter could be easily confirmed with transverse views. Since perforation was observed where the valve was attached to the posterior leaflet of the mitral valve during the 39th administration of RF energy, ablation was discontinued. The other patient had Kent bundle in the posterior septum of the left ventricle. The tip of the catheter could be easily confirmed with sagittal views. Ablation was successful after the 4th administration of RF energy, but particulate contrast echoes appeared from the site of the tip of the electrode which had been used for ablation during the 4th RF delivery. When the delivery of RF energy was discontinued, the contrast echo disappeared, and a thrombus was found at the tip of the removed catheter. TEE in RF catheter ablation was helpful for confirming the site of the tip of the catheter and for early detection of complications. PMID- 8355402 TI - Anomalous origin of left coronary artery from pulmonary artery in a 54-year-old woman presenting ventricular tachycardia from anteroseptal scar. AB - We report a 54-year-old female with anomalous origin of the left coronary artery from the pulmonary artery who came to our hospital complaining of dizziness presumably due to ventricular tachycardia. Electrocardiography, echocardiography and myocardial scintigraphy were indistinguishable from anteroseptal myocardial infarction. Only coronary angiography enabled us to differentiate between atherosclerotic ischemic heart disease and anomalous origin of left coronary artery from the pulmonary artery. PMID- 8355403 TI - [Automatic analyzing systems for blood chemistry and urinalysis]. AB - We constructed two new automatic analyzing systems for blood chemistry and urinalysis. The blood chemistry system consists of centrifuge station, on-line allotting station, belt line, Hitachi 736 -60, -40, off-line allotting station, storage allotting station and sample stocker, these are connected with belt line. If only specimens are set and switched on, analytical process from serum separation to measurement is advanced automatically, and then printed out the analytical results, it is the highest speed of 1.8 test/sec, in the world. Urinalysis system consists of qualitative analyzing station, quantitative analyzing station and urinary sediment analyzer, two station are logically coupled with belt line. It is a unique system of urinalysis that qualitative and quantitative analysis of urine is logically done by computerizing program. PMID- 8355404 TI - [Hematological study in 27 patients with myelodysplastic syndrome (MDS)]. AB - The clinical, histologic, and cytogenetic features of myelodysplastic syndrome (MDS) were analyzed in 27 patients consisting of 21 males and 6 females (M: F ratio = 3.5:1) whose median age was 60.9 years. Analysis of the peripheral blood of the patients revealed pancytopenia (8 patients), bicytopenia (12), and cytopenia in one cell lineage (5). The patients had high serum iron value and low UIBC value. More than 20% of all erythroid cells in the bone marrow consisted of ringed sideroblasts in not only RARS patients but also RAEB, CMMoL, and RAEB-T patients. Morphological changes of the bone marrow cells were observed in patients with all types of MDS. Eighty percent and 60% of RAEB and RAEB-T patients, respectively, showed trilineage myelodysplasia. Chromosomal abnormalities were observed in 52% of MDS patients. The rate of leukemic transformation was high in RAEB, CMMoL, and RAEB-T patients. PMID- 8355405 TI - [Current status of ultrasound examination of the superficial organs (breast and thyroid)]. AB - The ultrasound examination of superficial organs began with the application of the breast and thyroid. After the development of the high resolution real-time echography, this method has also been used for the examination of the salivary gland, parathyroid and lymph nodes, and it has become an indispensable diagnostic equipment, owing to low price, high diagnostic accuracy rate, short examination time and no invasiveness. Recently, colour Doppler equipment has developed and it has altered the reliability of ultrasound. [Breast]. The real-time method brought about the evaluation of compressibility and mobility by the dynamic test, and the interruption of the borderline of the mammary gland was added to the diagnostic criteria for breast cancer. Colour Doppler imaging will become a useful method to diagnose tumours, by evaluating the vascularity, blood flow volume or flow velocity. For nonpalpable tumours, ultrasonically guided aspiration cytology and biopsy were devised and they showed good results. [Thyroid]. Thyroid echography, together with aspiration cytology, became an integral part of the diagnostic method for thyroid cancer, and the necessity of the X-ray of the thyroid has decreased. The accuracy rate for papillary carcinoma recorded more than 80%. In the screening, the detection rate of carcinoma is now 1%. The differential diagnosis between carcinoma and adenoma, which both have a follicular pattern, is a problem yet to be solved. [Parathyroid]. Hyperplasia and adenoma of the parathyroid show hypoechoic and hypervascular area. In addition, the salivary gland and lymph nodes can also be evaluated with echography. PMID- 8355406 TI - [Rheumatoid factors--recent advances in measurement techniques, their fine specificities and mechanisms of their production]. AB - Rheumatoid factors (RF) are autoantibodies directed to the Fc of IgG. RF are present in the blood and synovial fluid of most patients with rheumatoid arthritis, and are also commonly detected in Sjogren syndrome and other autoimmune diseases, in chronic infectious diseases such a viral hepatitis and subacute bacterial endocarditis, and even in healthy individuals at low titers. Although vast studies have been made so far, the precise mechanisms leading to RF production and the fine specificity of human RF have not been well delineated. In this report, we present recent observations of RF concerning the following items: 1) changes in measurement techniques, 2) biological significance of RF in diseased and healthy states, 3) analysis of specificity of RF, and 4) mechanisms inducing RF production. PMID- 8355407 TI - [The physician executive and laboratory tests]. AB - Sera Central Hospital was founded in 1953 as Sera District Medical Center under the auspices of the neighboring five towns. At that time, the hospital had 3 doctors, 10 nurses, and 20 beds. But now in 1992, we have 12 doctors, 53 nurses and 110 beds. The present medical specialists are physician (4), surgeon (2), orthopedist (3), pediatrician (1), clinical laboratory physician (1), and dentist (1). Although the yearly income and expenditures were well balanced until 1989, thereafter the income began to decrease insidiously and expenditures began to increase year by year. In this symposium titled "Suggestions for Clinical Laboratory Medicine by Experienced Hospital Directors," I must refer to the issue of "Clinical Laboratory Medicine Administrator's Standpoint". Recently, the unaccustomed phrase "Physician Executive" is occasionally heard as the details of medical care become more numerous and more intricate and economic efficiency is strictly persued. From this perspective, the clinical laboratory physician is responsible for managing the laboratory department with well disciplined knowledge and technique. Therefore, training as "Physician Executive" has developed naturally within the field of Clinical Laboratory Medicine. So, I cannot help coming to the conclusion that the management of a hospital, as a matter of course, will be entrusted to a doctor including clinical laboratory physician who can do his best for the citizens, for the patients, and ultimately for ourselves. PMID- 8355408 TI - [Laboratory medicine, my philosophy and prospect]. AB - I have been working in the field of laboratory medicine for 45 years including the period of working as a physician. During my career, some of my dreams in laboratory diagnosis have been realized, and some have not. Although the issues changed with time, our basic philosophy has not changed at all. In this session, I would like to discuss "my philosophy of laboratory medicine", that is, what I have intended and what I have done. First, I describe the role of laboratory medicine in the field of clinical medicine. Second, I discuss the value of laboratory tests especially for clinical diagnostics. Third, I summarize the history of clinical pathology with reflection of the past, and my anticipation for the future. Fourth, I mention about the task and responsibility of the laboratory technicians and clinical pathologists, in view of their common purpose, clinical diagnosis. Finally, I discuss the future aspect of laboratory medicine. PMID- 8355409 TI - [The future of clinical laboratory medicine--a viewpoint from hospital administration]. AB - Net profits estimated from the operation of about 10,000 public and private hospitals here in Japan, showed a 0.6 per cent decrease in 1991. This reflects the severity of hospital management under governmental policy requiring the rate of increase in medical expenses to be less than the rate of increase for the GNP. Changes in medical fee reimbursement in the National Health Insurance in April 1992, reduced the fees for many medical tests, resulting in decreased income especially in outpatient clinics. Because of this, it is necessary to review the maintainance or existence of hospital laboratories from the standpoint of medical needs and cost efficiency. Laboratory tests must be done promptly, even on holidays. Only hospital laboratories can do this. Many bedside tests will need to be instituted. Doctors preferably, or technicians should fully explain the need for tests to the patient. "Informed consent" is important. Test results should be reported to the doctors not only with the test data, but also with interpretation by clinical pathologists to expedite the doctor's decision or diagnosis. The need for commercial laboratories is increasing because of difficulty caused by new and expensive equipment and techniques of modern laboratory service even in large hospitals. Commercial laboratories should serve not only as a subcontractor, but also as symbiotic partner of hospitals, clinics or medical offices in both medical and business management. PMID- 8355410 TI - [What is the ideal attainment of clinical laboratory works?]. AB - This is the specified address delivered at the 20th meeting of the Chugoku Shikoku District of the Japanese Society of Clinical Pathologists (JSCP). More than 40 years have elapsed since the incipient epoch of clinical pathology in this country, when physicians, surgeons and pathologists gathered, for the first time, to institute a scientific medical association (JSCP) for the purpose of elevating daily medical services to the modernized level through active use of clinical laboratory examination. Since then the laboratory examination has undergone a rapid progress and many new techniques have appeared. Excellent equipments and reagents are being supplied from the engineering and pharmaceutical companies. Thus, the clinical laboratories have assumed an out look of a big factory equipped with a variety of automatic analysers and a large number of computers, and the figures of many laboratory staffs are peeped among them. In this situation there arose several problems urgently needed for control to hole the laboratory ideal in service to the medical doctors as well as to the patients. 1. Management of personnels (medical technologists and others) who are dissatisfied with daily robot-like works and discordant human relations. 2. Report sheets sent to the medical doctors are not employed adequately for the care of patients, because they are handed over in uncooked style without clinical laboratory interpretation and recommendation. Therefore, the laboratory medical doctors are ranked below the medical doctors on the wards and outpatient clinic. 3. Too many tests are ordered to the laboratory without adequate recognition of their usefulness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355412 TI - [Evaluation of a one step sandwich enzymeimmunoassay for serum erythropoietin- serum erythropoietin values in polycythemia vera and related hematological disorders]. AB - We evaluated a newly developed enzymeimmunoassay for serum erythropoietin (Epo) and investigated relationship between Epo levels and hematological disorders. This method has several advantages including simplicity, high sensitivity, good precision. Moreover, the procedure requires only about 2.5 hours. Samples from 134 healthy subjects showed a normal logarithmic distribution, and its normal range was 4.5 approximately 21.3 mU/ml. The levels of Epo in normal subjects and various hematological disorders were as follows: 10.5 +/- 4.1 (mean +/- SD mU/ml) in normal subjects, 2.2 +/- 1.7 in polycythemia vera (PV), 6.1 +/- 3.1 in essential thrombocythemia, 17.8 +/- 27.3 in chronic myelogeneous leukemia, 3.6 +/ 1.8 in stress erythrocytosis, 39.4 and 14.1 in two cases of primary myelofibrosis, 1289 +/- 4798 in iron deficiency anemia and 6564 +/- 10870 in aplastic anemia. In patients with PV, serum Epo were low and did not correlate with hemoglobin concentration. However, inverse correlation was found between changes of Epo levels and hemoglobin levels in most patients. In cases in which PV progressed into myelofibrosis, anemia developed and Epo levels increased accordingly. These results suggest that the method is thought to be useful and reliable for the diagnosis and monitoring of PV and related hematological disorders. PMID- 8355411 TI - Mayo Clinic Laboratory Medicine: present and future. PMID- 8355414 TI - [Clinical markers in endocrine-metabolic diseases]. AB - We attempted to reevaluate the clinical significance of two parameters, 1,5 anhydroglucitol (AG) and type IV collagen, which are widely available in the fields of clinical activity. 1) 1,5 AG 1,5 AG was measured as a marker of glycemic control for diabetic patients by means of a column-enzymatic test (Nippon Kayaku Co., Ltd). Serum 1, 5 AG levels in diabetic patients (3.0 +/- 5.8 micrograms/ml, mean +/- SD) were significantly lower than in normal subjects (22.4 +/- 6.9 micrograms/ml). 75 g OGTT was performed on 428 subjects with urinary glucose detected on previous medical examination. According to the selectivity index (sensitivity value x specificity value) and the receiver operating characteristic curve (ROC) for diabetes, glycosylated hemoglobin (HbA1c) was slightly superior to 1,5 AG and fructosamine for diabetes screening. Furthermore, unexpectedly high levels of 1, 5 AG were obtained from the plasma of diabetic patients with this kit, when the patients were given a drip infusion containing maltose. We found that the maltose contained in the assay system interfered with measurement of 1, 5 AG. Nevertheless, 1, 5 AG measurements are thought to be useful in the diagnosis and screening of diabetes mellitus because of its wideranging fluctuations under relatively good glycemic control, as suggested by Yamanouchi, et al. 2) type IV collagen The type IV collagen peptide is known as a useful marker of progressive liver diseases and early stages of diabetic nephropathy. Type IV collagen was measured by one step sandwich enzyme immunoassay (EIA) using monoclonal antibodies (Panaassay IV CL; Fuji Chem. Ind., Ltd).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355413 TI - [Factor VII for a molecular marker in hypercoagulable state]. AB - We measured factor VII activity and antigen levels in plasma of pregnant women and patients with elevated serum FDP including patients with DIC who were supposed to be in hypercoagulable state, and compared the values with normal subjects. Both FVII activities measured by human placenta thromboplastin (hTF/FVIIc) and bovine brain thromboplastin (bTF/FVIIc) in normal plasma were correlated well with the FVII antigen levels (FVIIag). Measured hTF/FVIIc, bTF/FVIIc and FVIIag in pregnant women were 163 +/- 44%, 205 +/- 49% and 175 +/- 44% respectively, and each value had correlation. Thrombin-antithrombin III complex in these subjects was increased (7.85 +/- 2.25 mg/ml). However, antithrombin III, plasmin-plasmin inhibitor complex and FDP D-dimer were within normal range. These observations indicated that pregnant women were in hypercoagulable state but not in hyperfibrinolytic state. hTF/FVIIc, bTF/FVIIc and FVIIag in plasma from patients with elevated serum FDP were 59.6 +/- 29%, 94 +/- 65% and 61.6 +/- 26% respectively. We divided these patients into 2 groups: Group A (both prolonged PT and APTT) and Group B (shortened APTT). hTF/FVIIc, bTF/FVIIc and FVIIag in plasma of Group A were 47 +/- 21%, 48 +/- 24% and 48 +/- 21% respectively. The corresponding values of Group B were 80 +/- 24%, 155 +/- 54% and 74 +/- 23% which were correlated each other. Low levels of FVII observed in Group A seemed to be due to increased consumption of coagulation factors. In Group B, the pattern of FVII activities and FVII antigen was similar to that of pregnant women, though FVII levels were lower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355415 TI - [Detection of drug resistant-gene in cisplatin-resistant colon carcinoma cells by RT-PCR assay. I]. AB - Expression of the TS and DNA polymerase beta genes as a drug resistant-gene were compared with the human colon carcinoma cell line HCT8S and a subline that was 4.5 fold resistant to cisplatin. Resistant cells (HCT8DDP) exhibited 3.4 fold and 2.5 fold increase in mRNA for both TS and DNA polymerase beta gene when compared with the parent cells by Northern blotting analysis, respectively. The RT (reverse transcription)-PCR (polymerase chain reaction) method has been modified to quantify a sequence of a drug resistance gene. This method exhibited greater sensitivity than conventional methods (Northern blotting analysis), requiring less than 1 fetogram of mRNA from cell lines. The RT-PCR assay could be an effective device in the early detection of resistance to chemotherapy. PMID- 8355416 TI - Brown adipose tissue thermogenesis as physiological strategy for adaptation. PMID- 8355417 TI - Sleep and respiration under acute hypobaric hypoxia. AB - The purpose of this study was to elucidate the effects of acute hypobaric hypoxia on nocturnal sleep architecture and respiratory responses in a hypobaric simulator. Five healthy young males (19-23 years old) were recruited to sleep for 8 h at sea level and at simulated altitudes of 1,500, 3,000, and 4,000 m in the simulator (61.2 m3, 20 degrees C, and 60% RH). Each experimental run was separated by at least 3 d. Standard polysomnograph, respiration, and arterial oxygen saturation (SaO2) during sleep were observed. 1) SaO2 decreased significantly with increasing altitude. At 4,000 m, SaO2 showed its lowest value during 1 to 3 h after sleep onset. 2) Sleep architecture below 3,000 m showed almost the same pattern. However, reduction in REM sleep and increased wakefulness were observed at 4,000 m, though such sleep disturbance was not observed in the first one-third of the night spent in bed. 3) Periodic breathing (PB) with apnea and/or hypopnea developed in all subjects above 3,000 m. PB tended to appear in light sleep, though sleep was not always disturbed by PB. It might be concluded that there was no sleep disturbance up to 3,000 m altitude. Nocturnal sleep at 4,000 m, however, was disturbed after a few hours from sleep onset by severe hypoxemia induced by multiplicative effects of hypoxia and hypoventilation during deep sleep. At high altitude, PB seems to not induce arousals consistently, which was different from sleep apnea syndrome at sea level. PMID- 8355418 TI - Characterization of functional antagonism of adenosine and isoproterenol in guinea-pig atrial myocytes. AB - The role of adenosine action in modulating the action potential duration (APD) of single isolated guinea-pig atrial myocytes during beta-adrenergic stimulation with isoproterenol was investigated. Membrane potential and ionic currents were measured by the tight-seal, whole-cell patch-clamp technique. Adenosine (10 microM) antagonized isoproterenol (20 nM)-stimulated L-type calcium inward current (ICa). In the presence of isoproterenol, adenosine (10 microM) also increased holding and late outward currents. Isoproterenol (20 nM) caused a significant prolongation in atrial action potential at the level of 0 mV, rather than at 90% repolarization. Adenosine shortened atrial action potential dose dependently in the presence of isoproterenol. The respective values for EC50 and maximally shortened action potential duration at 0 mV of adenosine with or without isoproterenol (20 nM) were 3.0 vs. 2.2 microM and 42.9 vs. 30.4 ms. In summary, during beta-adrenergic stimulation with isoproterenol, in guinea-pig atrial myocytes, adenosine elicited the specific K(+)-outward current and concomitantly attenuated the isoproterenol-stimulated ICa. These phenomena may account for the modulation of atrial action potential by adenosine with or without isoproterenol effect. PMID- 8355419 TI - Impaired fibrinolysis in hypertension and obesity due to high plasminogen activator inhibitor-1 level in plasma. AB - In order to elucidate the influence of the risk factors of coronary heart disease on the fibrinolytic activity, relationships between blood pressure, body mass index (BMI), plasma lipoprotein (a) (Lp(a)) level and the plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were analyzed in the subjects with mild hypertension. Systolic blood pressure showed a positive correlation with total PAI-1 and free PAI-1. Diastolic blood pressure showed no correlation with these proteins involved in the fibrinolytic system. BMI had a positive correlation with total PAI-1, free PAI-1 and euglobulin clot lysis time (ECLT). Plasma Lp(a) level showed correlation with neither blood pressure nor fibrinolytic parameters, but it showed weak negative correlation with body mass index (BMI). These results suggest that high blood pressure and obesity tend to increase free PAI-1 which reduces fibrinolytic activity. Lp(a), however, seems not to influence directly the fibrinolytic system but may work to decrease fibrinolytic activity only in conjunction with other risk factors. The effects of daily drinking of alcohol and smoking on the fibrinolytic system were also investigated in the present study and we obtained the results that habitual drinking increased plasma levels of both tPA and PAI-1 whereas smoking did not affect fibrinolytic activity. These results suggest that risk factors for coronary heart disease such as hypertension and obesity are closely related to the impaired fibrinolysis. PMID- 8355421 TI - Time course of acid-base regulation following intraperitoneal CO2 administration in man. AB - Chronological changes in acid-base status during laparoscopic CO2 insufflation were studied for 2 h in 10 patients who underwent laparoscopic cholecystectomy. Carbon dioxide pressure in alveolar air as well as arterial blood promptly and significantly increased within 5 min whereas amount of pulmonary CO2 elimination significantly increased after 15 min. Pulmonary gas exchange ratio (R) exceeded the level of unity at 10 min and progressively increased toward the end of 2 h observation. These results indicated that CO2 equilibrium process between different body compartments with different time constant took place and apparent equilibrium was not completed during observation. In vivo buffer value of the arterial blood started to decrease after 5 min and decreased to about one-third the in vitro buffer value until the end of observation. This indicated that CO2 equilibrium between blood and interstitial fluids took place slowly during entire period of study and no significant contribution of cellular buffering was developed. We conclude that slower development of acid-base regulation in the present study than those reported in the previous studies may have been derived from small diffusion area and blood perfusion for CO2. PMID- 8355420 TI - Inhibitory effects of cyanide on mechanical and electrical activities in the circular muscle of gastric antrum of guinea-pig stomach. AB - Effects of cyanide (CN) on spontaneous mechanical and electrical activities were studied in the circular muscle of the guinea-pig gastric antrum. CN (0.05-0.5 mM) inhibited both mechanical and electrical activities, but the inhibition was stronger in the former than the latter (slow wave). When glucose was removed for more than 30 min, slow wave was also blocked by CN. It is likely that ATP necessary for the generation of spontaneous activity can be supplied through either glycolysis or oxidative phosphorylation. CN slightly depolarized the membrane and the inhibition by CN was not affected by glibenclamide, a blocking agent of ATP-regulated K+ channel, suggesting that this channel is not activated by CN treatment. Basal level of intracellular Ca2+ measured with fura-2 tended to increase during the mechanical inhibition by CN. This was also clearly demonstrated in excess (60 mM) K+ solution. These results suggest that intracellular Ca2+ regulation is impaired and that there is uncoupling between intracellular Ca2+ and tension development in the presence of CN. PMID- 8355422 TI - Lipolytic actions of hormones on adipocytes in exercise-trained organisms. AB - Adipocytes from sportsmen exhibited lower basal rate of lipolysis but higher response to adrenaline than those from untrained persons. Dexamethasone exposure for 30 min enhanced the adrenaline effect both in sportsmen and trained rats. Insulin abolished this glucocorticoid action. A rapid permissive action of glucocorticoids was suggested in the trained organism. PMID- 8355423 TI - Effects of cardioplegic reperfusion on ATP recovery of rod-shaped myocytes isolated from rat ventricles. AB - ATP content [ATP] and fraction of rod-shaped myocytes (Rrod) were measured in ventricular myocytes isolated from the rat heart. [ATP] (nmol (10(6) cells)-1) and Rrod (%) were 72.0 and 60.5, respectively, and significantly reduced to 18.8 and 41.8 by no-flow ischemia for 30 min. Reperfusion for 15 min with cardioplegic solutions restored [ATP] of rod-shaped myocytes to the control level. PMID- 8355424 TI - An improved method for perforated patch recordings using nystatin-fluorescein mixture. AB - This paper describes an improved method for solubilizing nystatin in an aqueous solution without the aid of organic solvents. The patch pipette was filled with a solution of nystatin and fluorescein sodium mixed in a molar ratio of 1:10. The success rate of perforated patch recordings was substantially improved, and the access resistance of 20-40 M omega was readily achieved. PMID- 8355425 TI - [Self-efficacy predictiveness and its determinants among preschoolers]. AB - Precision of self-efficacy predictions on a ball-throwing task was compared between the younger group (3-year-olds; N = 40) and the older group (5-year-olds; N = 40). Three factors underlying the development of accurate efficacy expectations were examined. They were the effect of experience, the complexity of the task, and information of task performance. Results indicated that the predictions of the older group were more accurate than those of the younger group, and their predictions were significantly related to subsequent performance. They did more realistic efficacy predictions by using information of task performance and experience. The younger group showed no accuracy of self efficacy predictions. But the presentation of information about task performance enabled them to make realistic efficacy predictions. PMID- 8355426 TI - [The effect of group size on salience of member desirability]. AB - This study tested the hypothesis that undesirable members are salient in a small group, while desirable members become salient in a larger group. One hundred and forty-five students were randomly assigned to twelve conditions, and read sentences desirably, undesirably, or neutrally describing each member of a college student club. The twelve clubs had one of three group sizes: 13, 39, or 52, and the proportion of the desirable or undesirable to the neutral was either 11:2 or 2:11, forming a three-way (3 x 2 x 2) factorial. Twelve subjects each were asked to make proportion judgments and impression ratings. Results indicated that proportion of the undesirable members was over estimated when the group size was 13, showing negativity bias, whereas proportion of the desirable was overestimated when the size was 52, displaying positivity bias. The size 39 showed neither positivity nor negativity bias. These results along with those from impression ratings suggested that salience of member desirability interacted with group size. It is argued that illusory correlation and group cognition studies may well take these effects into consideration. PMID- 8355427 TI - [A study on job satisfaction of clinical psychologists working in the medical field]. AB - The purpose of this study was to examine the relationship of job satisfaction to job difficulty and worthiness, reported by the clinical psychologists who worked at medical institutions. A mail survey of 748 clinical psychologists working at hospital and clinics revealed the following results. First, job satisfaction was related more to job situation than job content. Also, job satisfaction was low among those who worked at non-university psychiatric or geriatric hospitals, who did not practice psychotherapy, and who were not in education, research, or management. In addition, compared to the high job satisfaction group, the low group perceived more incongruity between institutional climate and their psychological work, felt being less valued by other professionals, were less able to function fully as a practicing psychologist, and experienced more role ambiguity as a clinical psychologist in a hospital setting. PMID- 8355428 TI - [A study of organizational communication in a school during the pre- and post innovation periods]. AB - The purpose of this study was to examine changes in organizational communication behavior in an elementary school during the pre- and post-innovation periods. The turning point of the pre- and post-innovation periods were determined by transference of decision making systems in the school. Data were collected through participant observation, and the analyses indicated the following results. Compared to the pre-innovation period, during the post-innovation period, 1) overall communication level increased; 2) discussions, rational persuasion , and proposals increased, while assertions decreased as the contents of communication; and 3) the number of those who spoke at teaching staff meetings increased. Concerning downward communication, 1) rational persuasive communication was used most frequently throughout the pre- and post-innovation periods; and 2) communication suggesting a compromise increased during the post innovation period. These findings were discussed in terms of organizational effectiveness of the school. PMID- 8355430 TI - [Effects of loud noise on nasal skin temperature]. AB - It has been demonstrated that stress conditions for babies such as a brief mother infant separation cause the nasal skin temperature to drop. Changes in skin temperature may be taken as a representative sample of bodily reaction correlated with emotional changes. The purpose of this study is to investigate nasal skin temperature changes under loud noise situation. Fifty-two undergraduates were divided into two groups. Each group had 13 male and 13 female subjects. One group was given 100 dB and another was given 45 dB white noise. The Infrared Telethermograph Imager was used to measure nasal skin temperature changes. The results showed that the nasal skin temperature under 100 dB white noise decreased by about 0.5 degree C. However, under 45 dB no significant change was found. These findings suggest that the facial skin temperature will be one of the promising indices to detect various emotional changes. PMID- 8355429 TI - [Schizophrenia and reverse-Stroop interference in the group version of the Stroop and reverse-Stroop test]. AB - Previous studies showed that attentional task performance of schizophrenics was significantly inferior to that of normals. The classical Stroop Color-Word Interference Test is an example of such attentional tasks and performance on the "reverse" Stroop task is reported to discriminate schizophrenics from normals better than the regular Stroop task. These results suggest that schizophrenics are more susceptible to "reverse" Stroop interference in reading incongruent word color combinations than normals. The group version of the Stroop and reverse Stroop Color-Word Test, where the response is to choose a matching alternative, was used to test the hypothesis. The results virtually supported the hypothesis. In addition, interference was closely related to the patient's control of impulsiveness. It was suggested that schizophrenics have generation (or translation) deficits between different codes. PMID- 8355431 TI - [Effect of information generation on incidental memory of words]. AB - The present study was carried out to investigate the effect of information generation on incidental memory of words. Subjects in the subject-generated group were asked to generate a converging associate of three targets in each triplet. Subjects in the experimenter-provided group were asked to rate the relation between targets and a paired-presented word on 5-point scale. Each subject in both groups were given an unexpected free recall test. Recall performance for targets in each unrelated triplet in the subject-generated group was higher than in the experimenter-provided one. Conditional probability of recalling targets given relational information was an index of effectiveness of within-item elaboration. This index was higher in the subject-generated group. These results were interpreted as showing that the effect of information generation was caused by the effectiveness of within-item elaboration. PMID- 8355432 TI - [Observation of the effects of warming-up and role-playing in psychodrama in terms of mood rating]. AB - The purpose is to make an appropriate list of terms that describe person's moment to-moment changes in moods during psychodrama sessions. Seventy nurse students participated in a series of psychodrama sessions, consisting of a session of warming-up and two sessions of role playing. They rated their moods at the beginning of the sessions and after each session, on a five-point scale for each of the 55 terms, which were supposed to cover all kinds of moods during psychodrama sessions. After analyzing variations (using factor analyses) of subjects' ratings, three factors were found to be sufficient for describing their moods, and the terms in the list were eventually reduced to sixteen. Changes of moods analyzed through the ratings of sixteen scales were related significantly with subjects' performances of warming-up and role playing. PMID- 8355433 TI - [Short intertrial interval as a phrasing cue in the reinforcement-pattern learning in rats]. AB - The effect of short intertrial interval as a phrasing cue on the reinforcement pattern learning was investigated in a rat experiment using a runway. In the acquisition session, 20 rats were trained for NNR sequence in which two nonreinforced trials were followed by a reinforced one with equal ITI of 30 min. In the sequence-addition session, a new sequence with consisting of three nonreinforced trials with 30-min ITI was added 30 min and 30 s after the original sequence of trials for Group L-ITI and for Group S-INT, respectively. Rats of Group S-INT responded on trials 4-6 with the similar pattern of running speed as they showed on Trials 1-3 from the second day. In Group L-ITI, the running speed on Trial 4 did not decrease. This suggests that Group S-INT rats learn to use the ITI of 30 s as a phrasing cue not on the first day but from the second day on. The phrasing effect of short ITI (30 s) was discussed in comparison with that of longer ITI (30 min). PMID- 8355434 TI - [Recognition and categorization of butterfly patterns]. AB - Two experiments are reported which deal with the nature of categorization of visual patterns. Stimulus materials were schematic butterfly patterns. Systematic transformations of five physical features (fore wing, hind wing, size, body length and color) were applied to a prototype to generate a set of instances. In Experiment 1, subjects were asked to judge the visual similarity between each instance and the prototype. Similarity ratings were found to be related to an each instance's transformational distance from the prototype. In Experiment 2, subjects were exposed to a subset of instances of the pattern which varied in their transformational distance from the prototype, and then given a recognition test with confidence ratings. The recognition item consisted of the old and new instances including the prototype. Recognition ratings were found to be related to each instance's family resemblance score rather than its transformational distance and subjective similarity to the prototype. These results support Rosch and Mervis's family resemblance model of categorization. PMID- 8355435 TI - [Statistical analysis of recurrent factors in superficial bladder cancer. Natural history of superficial bladder cancer]. AB - Three hundred thirty-six patients with superficial bladder cancers underwent their initial surgery at the Department of Urology of Okayama University School of Medicine from 1961 to 1985. They have been followed-up until December 1988 (the median: 68 months). Among the 336 cases, excluding 9 cases which were treated initially with total cystectomy or incomplete resection, the remaining 327 cases were reviewed in order to study the pattern of their local recurrences in the bladder. Major factors affecting recurrences of superficial bladder cancer were evaluated by the multivariate analysis using Cox's proportional hazard model. The examined factors included age on admission, sex, tumor's number, size, stage, histological grade and shape, operative method, intravesical chemotherapy, systemic chemotherapy, radiotherapy, frequency of recurrences and the date of operation. During the follow-up period, 179 cases out of the 327 cases did not show any recurrences. The remaining 148 cases recurred from once to 11 times, therefore, a total number of recurrences was counted to be 406. In the 406 recurrences, 338 recurrences were treated by TUR, SVR, or SR. The remaining 68 recurrences were treated with total cystectomy or untreated. Fifty-seven cases out of the 148 cases demonstrated recurrences more than 3 times. Only 4 cases were free from recurrences more than 24 months following the surgery for their last recurrences. The analysis in the 327 primary cases showed that the number of tumors was the most important factor. On the other hand the analysis in 338 recurrences showed that the second most important factor was the frequency of recurrences, following the number of tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355436 TI - [Tissue concentration of intravesically instilled (2"R)-4'-o-tetrahydropyranyl adriamycin or adriamycin in superficial bladder cancer]. AB - Twenty-one patients with superficial bladder cancer entered an analysis of single dose (2'R)-4'-O-tetrahydropyranyladriamycin (THP) or adriamycin (ADM) administration. The patients in each group that have been or not have been treated previously with anti-cancer drugs were randomized into two groups, one was given THP and the other ADM. Thirty-mg of THP or ADM dissolved in 30 ml of physiologic saline was instilled into the bladder, and retained for 1 hour. After 1 hour retention of the drugs, tumor tissues and normal mucosas were removed by punch biopsy forceps transurethrally. The tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. The tissue concentrations of THP and ADM in the tumors were significantly greater (p < 0.05) than those in the normal bladder mucosas. The tissue concentration of THP in the tumors were greater than that of ADM. The tissue concentrations of THP and ADM in the tumor of patients who have been treated with anti-cancer drugs previously were less than those of patients who have not. This results demonstrated that prior therapy with anti-cancer drug may cause a resistance for intravesical instillation chemotherapy. However in patients with prior therapy, the tissue concentration of THP in the tumors were greater than that of ADM. Based on these findings, THP has been shown to be were effective as an intravesical instillating agent especially, in cases with prior chemotherapy. PMID- 8355437 TI - [Autologous blood transfusion in transurethral resection of the prostate]. AB - With the purpose to avoid the risk of transfusion mediated infection and complication, predeposited autologous blood transfusion was performed. From April 1990 to March 1991, transurethral resection of the prostate (TUR-P) were performed in 27 patients (mean age: 72.5 years) with benign prostatic hypertrophy (BPH). Autologous blood (200-400 ml, mean 244 ml) was predeposited 3 weeks prior to TUR-P in 18 patients (mean age: 73.9 years) and transfused during or just after the operation in 16 (five patients required some homologous blood in addition to their own banked blood). Another three patients were transfused with homologous blood only. The mean values for hemoglobin concentration were 13.7 +/- 0.4 g/dl before blood deposition and 12.8 +/- 0.5 g/dl on the day of operation (recovery rate: 92.5 +/- 2.7%). Although no complication was found in autologous blood transfusion group (11 patients), one case of systemic exanthema and one case of type C hepatitis were observed in homologous blood transfusion group (8 patients). In TUR-P, positive correlations were observed among resected prostate weight (Pro-wt), blood loss (B.) and operation time (Op-T.). Correlation efficient between Pro-wt. and B. was 0.80, that of B. and Op-T. was 0.77 and that of Pro-wt. and Op-T. was 0.85. From these results and ultransomographic measurement of the prostate weight, the amount of blood loss can be calculated preoperatively, there by the amount of blood needed for transfusion will be estimated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355438 TI - [Phenotypic difference of lymphocytes circulating in tumorous renal artery and renal vein in patients with renal cell carcinoma]. AB - Phenotypic difference of lymphocytes circulating in tumorous renal artery and renal vein in patients with renal cell carcinoma was studied. Fifteen patients with no prior treatment were studied, from whom blood samples were taken at the time of radical nephrectomy. Mononuclear cells separated from tumorous renal arterial and venous blood were analyzed for cell surface markers. CD3, CD4, CD8, CD11b, CD16, CD25, CD57, Leu8 HLA-DR were compared. CD25 positive cells were significantly increased in venous blood than in arterial blood in the kidneys with tumor. No significant difference was found regarding the other surface markers. PMID- 8355439 TI - [Effect of hydronephrosis on the contralateral blood flow and glomerular volume]. AB - We designed a following experiment to appraise the effect of unilateral hydronephrosis on the contralateral kidney using weanling rats whose kidneys were in a growing stage. Rats were divided into 4 groups. Complete unilateral (left) ureteral obstruction (CUUO) was made on the experiment rats, and these went through the following procedures on the day 3 after CUUO; 1) Group R: CUUO released, 2) Group N: left nephrectomy performed, 3) Group S: CUUO continued. Sham-operations were performed on the days 0 and 3 to the controls. Renal cortical blood flow and glomerular volume of the contralateral (right) kidneys were determined on the days 5, 7, 9, 14 and 21. Blood flow to the renal cortex per unit volume (ml/min/100 cm3; measured with Laser blood perfusion monitor) in the contralateral kidneys increased gradually in the all groups, but statistical significance was not confirmed in the observed period between any groups. Increases in total renal blood flow (wet kidney weight times renal cortical blood flow per unit volume; g x ml/min/100 cm3) were proportional to the measured wet kidney weight in the all groups. Notably in the group N, a significant increase was noted compared to the group R and the controls. Glomerular volume (GV) of the contralateral kidneys did not show significant changes on the day 3 compared to the controls. GV significantly grew up during the day 5 to the day 14 (2 to 11 days after the relief of CUUO) in the group R and then it settled to the level of the controls on the day 21.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355440 TI - [A study of muscarinic cholinergic receptor subtypes in human detrusor muscle using radioligand binding techniques]. AB - The subtypes of the muscarinic cholinergic receptor in human detrusor muscle were studied using radioligand binding techniques. It was found that there were significant amount of M1, M2 and M3 receptors labeled by 3H-pirenzepine, 3H-AFDX and 3H-4DAMP, respectively, in human detrusor muscle. The rank order of the amount of these receptors was M3 > M1 > or = M2. The amount of M3 receptors was about 10-fold of M1 or M2. In the inhibition experiment of 3H-QNB binding to human detrusor muscle, the Ki values of pirenzepine or AFDX was 50-100 fold of that of 4DAMP and the rank order of Ki values was pirenzepine > AFDX > 4DAMP. The M3 selective drug, 4DAMP showed smallest Ki value among the three drugs studied, indicating that the affinity of M3 receptor was highest among the three muscarinic subtypes. These data suggest that M3 receptors are predominant in human detrusor muscle biochemically. PMID- 8355441 TI - [The surgical management of renal cell carcinoma involving the right atrium]. AB - Between January 1985 and November 1992, 12 patients with renal cell carcinoma involving the inferior vena cava were evaluated and treated at this hospital. In 4 of the 12 patients (33%), the tumors extended into the right atrium. These 4 patients underwent radical nephrectomy with tumor thrombus extraction. Of the 4 patients one had metastases to regional lymph nodes, but no patient had distant metastases. We used a cardiopulmonary bypass and a right atriotomy in all patients for the removal of thrombus under direct vision. We also performed in the intra-operative transesophageal ultrasonography for monitoring of intra atrial thrombus. The average blood loss during operation was 10,430 ml. One of these patients died in the postoperative period and the other patient died from inferior vena caval emboli without long term sequelae. However, the remaining 2 patients of this group are free of disease, with a mean follow-up of 21 months. Although the numbers are small, these results suggest that patients with intra atrial tumor thrombus had a worse prognosis than those with other types of vena cava tumor thrombus. One reason for this poor prognosis is due to the complicated surgical management and we believe that a complete removal of tumor thrombus and a complete vascular control are key points of this operation. PMID- 8355442 TI - [Treatment of urinary tract anomalies detected by prenatal ultrasonography]. AB - Twelve pediatric patients with antenatal diagnosed urinary tract anomalies from 1988 to 1992 in Niigata University Hospital were clinically examined. 1: All patients were diagnosed by ultrasonography. Eleven cases did not have any abnormal pregnancy and other had oligohydramnious. 2: Postnatal surgical treatments were performed in 11 cases, but antenatal therapy was not performed in any case. 3: Temporary percutaneous nephrostomy (PNS) were carried out on 7 kidneys in 6 cases during infantile period seems to be effective in preserving function of congenital obstructed kidneys. PMID- 8355443 TI - [Evaluation of bladder tumor staging by submucosonography]. AB - Submucosonography to stage tumors of the esophagus and stomach is well reported. Here we report our experience with a modified procedure to evaluate the stage of bladder tumor cystoscopically and compare the results of staging by other methods. The evaluation was carried out on accuracy 10 patients (10 bladder tumors). A water soluble contrast medium (CM: lohexol 33 mg/ml) was injected into the submucosa of the bladder cystoscopically. Usually the injected point was one centimeter to the urethral margin of the tumor and up to three points were selected. Within 30 minutes after the injection, the lateral and frontal X-ray pictures were taken. The accuracies of staging by submucosonography were compared with the results of other methods, i.g., ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI). By submucosonography, three categories depending on the diffusion of CM were classified as follows. Type I: (diffuse type) without disturbance of diffusion. Type II: (borderline type) between type I and III. Type III: (defect type) local disturbance of diffusion. Overall accuracies of each were 70.0% (submucosonography), 62.5% (US), 44.4% (CT), 66.7% (MRI) respectively. The accuracies of submucosonography were high in stage Ta, above stage T2 and low in stage T1. PMID- 8355445 TI - [Study of immunosuppressive mechanism of deoxymethylspergualin in vitro]. AB - Mechanism of action of Deoxyspergualin (DSG) in vitro has not been clarified, because it is unstable in solution. I studied its mechanism in vitro using Deoxymethylspergulin (MeDSG) that is stable in solution. Action of MeDSG was studied using human lymphocyte and a human T cell clone which was established in our laboratory. MeDSG showed dose dependent inhibition of blastogenesis in MLR. MeDSG inhibited the response by about 50% at the concentration of 10 micrograms/ml. It is a very interesting point that MeDSG added at 3 days later suppressed MLR. But MeDSG did not suppress MLR added at 4 days later or 2nd MLR. MeDSG did not have effects on the production of IL-1, IL-2 and the expression of IL-2 receptor on stimulated lymphocyte by mitogen. But MeDSG suppressed IFN-gamma production induced stimulation of alloantigen at only concentration of 1 microgram/ml. MeDSG did not suppress proliferation of helper T cell clone. On the other hand, CsA suppressed IL-2 receptor expression and proliferation of helper T cell clone. These results showed MeDSG act on relatively late phase of immunoreaction. From in vitro results, when we use DSG for clinical acute rejection, it is more appropriate to use DSG and Methylprednisolone at the same time to get early recovery. PMID- 8355447 TI - Eosinophilia-myalgia syndrome and fasciitis with an active alveolitis. AB - This patient clearly had the EMS with eosinophilic fasciitis, apparently due to L tryptophan. He also had an active alveolitis with a DIP-UIP-like picture. The lung findings were not similar to those reported in the Mayo series. It is perhaps most likely that his interstitial lung disease was of the cryptogenic variety and unrelated to the L-tryptophan. However, a more direct association cannot be ruled out until more cases with similar findings are thoroughly evaluated. We suggest that special consideration of pertinent studies for interstitial lung disease is merited in all patients with suspected EMS. These might include diffusing capacity, gallium scans of lungs, broncho-alveolar lavage and possibly lung biopsy. PMID- 8355446 TI - [A case report of an ectopic ureter in a patient treated for chronic prostatitis]. AB - A male aged 20 had been treated for anal and lower abdominal pain after ejaculation for about 2 years under the diagnosis of chronic prostatis. Because of worsening of the pain, he was admitted to our hospital in September 24, 1991. On the rectal examination, a cystic tumor was palbable on the left side of the prostate. The left kidney was not detected by IVP and ultrasonography. CT revealed two retrovesical cystic lesions in the left side. Cystourethroscopy showed an absence of ureteral orifice and ureteral ridge on the left side. Left uretero-seminal vesiculectomy was performed on October 3rd, under the diagnosis of an ectopic ureter entering into the seminal vesicle or ejaculatory duct. Histopathologically, the left ectopic ureter entering into the lower portion of the seminal vesicle or ejaculatory duct and the left renal agenesis were diagnosed. It was remarkable that ureteral epithelium was not transitional but columnar epithelium. PMID- 8355444 TI - [Expression of progesterone-binding protein in normal and neoplastic human adrenals]. AB - Specific progesterone-binding protein (P4-BP) is demonstrated in adrenocortical nuclei of the guinea pig, but, not in nuclei of other animals. We tried to demonstrate the progesterone-binding activity in nuclei of human normal adrenals and adrenal tumors. Normal adrenals were obtained from six patients with renal cell carcinomas undergoing radical nephrectomy. Seven adrenocortical adenomas were obtained: five tumors from patients with Cushing's syndrome, one tumor from non-functioning adenoma, and one from aldosteronoma. Nuclei were purified from the tissues, and progesterone binding assay was performed. We could not demonstrated progesterone-binding activity in nuclei of six normal human adrenals. However, we demonstrated progesterone-binding activity in nuclei purified from human adrenocortical adenomas associated with Cushing's syndrome. Saturation analysis revealed a Kd of 13.85 +/- 1.99 nM (mean +/- SD, n = 5) and a binding capacity of 1.95 +/- 0.37 pmol/mg DNA (mean +/- SD, n = 5). A Kd of progesterone-binding activity in human adrenocortical adenoma was similar to that of guinea pig P4-BP, and a binding capacity was about one-fifteenth of guinea pig P4-BP. However, nuclei purified from a non-functioning adrenocortical adenoma and an aldosteronoma failed to demonstrate progesterone-binding activity. The binding activity was specific for progesterone. 5 alpha-pregnane-3,20-dione was a modest competitor, while 17 beta-estradiol, testosterone, cortisol, and other related steroids were poor competitors. Thus the progesterone-binding activity in human adrenals was similar to guinea pig P4-BP in the affinity and specificity of binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355448 TI - Stroke-free survival after infarction. PMID- 8355449 TI - Schistosomal glomerulopathies. PMID- 8355450 TI - Abnormal hemodynamics and elevated angiotensin II plasma levels in polydipsic patients on regular hemodialysis treatment. AB - To investigate the cause and the mechanisms responsible of the compulsive thirst and excessive fluid intake observed in many patients on chronic dialysis treatment, we measured plasma antidiuretic hormone (ADH), angiotensin II (Ang II) and some hemodynamic parameters in seven polydipsic and in six normodipsic patients before hemodialysis, at the end of it and several times during the interdialytic interval. Before dialysis we found that ADH was elevated in both groups (6.9 +/- 1.9 vs. 6.9 +/- 1.3 pg/ml, respectively in polydipsics and controls), whereas Ang II was abnormally high only in polydipsics (51 +/- 12 vs. 11 +/- 3 pg/ml, P < 0.01); these patients also had significantly higher heart rate and cardiac indices and lower total peripheral resistances than control patients. Overall these hemodynamic indices were related with Ang II but not with ADH. Ang II rose markedly in polydipsics after dialysis, reaching a peak at the fourth hour after its termination (136 +/- 12 pg/ml) and remained consistently elevated throughout the interdialytic period, whereas in controls Ang II was practically unchanged with respect to baseline. In contrast, ADH had minor and similar modifications in both groups, in whom also the hemodynamic changes were superimposable. Significant correlations were found between the absolute and percent changes of Ang II and those of plasma volume during the interdialytic interval (P < 0.001 for both), and between the individual values of Ang II measured during the whole study and the interdialytic weight gain (P < 0.05). These results demonstrate that polydipsic patients have abnormally high levels of Ang II before and after the hemodialysis-induced volume depletion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355451 TI - Serum albumin is a strong predictor of death in chronic dialysis patients. AB - We examined the predictive value of various clinical variables in assessing survival in chronic hemodialysis patients (N = 1,243, 524 females, 719 males) who were under treatment with hemodialysis as of January 1991 in Okinawa, Japan and who were followed up until April 1992. Basal clinical data such as sex, starting date of dialysis, primary renal disease, blood pressure, blood chemistry values, and dialysis prescription data obtained just prior to dialysis were registered at the start of the study. As of the end of April 1992, 104 had died, 16 were transplant recipients, and five had been transferred. Those who died had significantly lower levels of total protein, serum albumin, total cholesterol, triglyceride, BUN, serum creatinine, body weight, body height, diastolic blood pressure, and duration of hemodialysis than those who survived. Older patients and those with diabetes mellitus had a poorer prognosis. A forward stepwise logistic procedure by SAS was used to determine the predictive value of the above clinical variables. With the addition of laboratory variables, the predictive value of diabetes was lost, as the diabetic patients had low serum levels of albumin and creatinine. The standardized coefficient was -0.380 (P = 0.0001) at age of entry, 0.316 (P = 0.0001) for serum albumin, 0.280 (P = 0.0001) for serum creatinine, 0.138 (P = 0.043) for body mass index (BMI), and -0.139 (P = 0.016) for male sex. The prescribed dialysis dose (M2 hr per week) was significantly correlated with serum creatinine (r = 0.48, P = 0.0001), serum albumin (r = 0.135, P = 0.0001) and BMI (r = 0.275, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355452 TI - Calculation of titratable acidity from urinary stone risk factors. AB - Using urine samples and standard solutions, this study demonstrates that the existing procedure for measuring titratable acidity in the urine is not reliable and may result in overestimates of up to 25%. The accuracy is affected by loss of CO2, the presence of uric acid crystals, and the precipitation of calciumphosphate phases during the titration. A method is presented for calculating titratable acidity, using a number of routinely-measured urine components and a computer program for calculating complex equilibria in the urine. The calculated titratable acidity is shown to be more reliable then the measured one. The results are compiled in a nomogram from which the titratable acidity can be directly read. When the parameters of urine pH, PO4 content and pCO2 are used, the accuracy of the nomogram is > 96% for urine samples with a pH value above 6.0 and > 89% for urine samples with a pH value below 6.0. For all samples, the accuracy is improved to > 97% when the nomogram using uric acid and citrate content is used in additionally. PMID- 8355453 TI - Sodium-lithium countertransport and triglycerides in diabetic nephropathy. AB - Elevated erythrocyte sodium-lithium countertransport (SLC) activity is an intermediate phenotype of essential hypertension among Caucasians, and is controversially associated with nephropathy in Type 1 (insulin-dependent) diabetes. Hypertriglyceridemia is a frequent concomitant of elevated SLC in the general population, and may be found in diabetic nephropathy. The present study was designed to investigate the influence of kidney disease, serum triglycerides and blood pressure on the interindividual variability of SLC in Type 1 diabetes. SLC and fasting major serum lipids were studied in 35 Type 1 diabetic patients with persistently elevated urinary albumin excretion and in a group of patients matched for age, sex and duration of diabetes, but with normoalbuminuria. SLC was elevated in patients with clinical nephropathy (N = 10; median: 420 mumol.1RBC 1.hr-1) and in patients with microalbuminuria (N = 25; median: 405 mumol.1RBC 1.hr-1) compared with normoalbuminuric patients (median: 296 mumol.1RBC-1.hr-1; P < 0.01 vs. both groups). Hypertriglyceridemia and hypercholesterolemia were found only among patients with macroalbuminuria. Analysis of covariance indicated that the association of elevated SLC with kidney disease (P < 0.006 in all models) was largely independent of serum triglycerides, but also of total cholesterol, insulin dose and measures of glycemic control. Only diastolic blood pressure was positively associated with SLC (P < 0.02) independently from nephropathy (P < 0.005) also after restricting analysis to the normoalbuminuric patients. Kidney disease and raised blood pressure remain major concomitants of elevated SLC in Type 1 diabetics. PMID- 8355454 TI - Lower affinity for substrate for extrarenal synthesis of calcitriol in chronic uremia. AB - Previous studies from our laboratory have shown that anephric patients have very low, but detectable, levels of 1,25(OH)2D3 (calcitriol) that can be increased to normal by administration of large doses of 25(OH)D3. The report of 1 alpha hydroxylase activity in pig liver with an affinity for substrate significantly lower than that of the renal enzyme, led us to use the rat as an experimental model to further clarify the need of supraphysiological levels of 25(OH)D3 to correct calcitriol deficiency in chronic uremia. We have measured 1,25(OH)2D3 production by rat liver. Cytosol free liver homogenates (CFH) from normal rats were incubated with 25(OH)D3 and the production of 1,25(OH)2D3 was measured using the thymus radioreceptor assay after solid phase C18 extraction and HPLC purification of the samples. 1,25(OH)2D3 production was linear up to 30 minutes and a CFH protein concentration up to 20 mg. Saturability was attained for a substrate concentration of approximately 60 microM. Ketoconazole, a cytochrome P450 inhibitor, blocked calcitriol production in a dose dependent fashion. Total inhibition of the liver 1 alpha-hydroxylase was achieved with 180 microM ketoconazole. We next compared the kinetics of the 1 alpha-hydroxylases of normal and uremic rat livers. Maximal velocities were not statistically different (139.6 +/- 22.3 pg/mg/min for normals and 217.1 +/- 73.3 pg/mg/min for uremic rats). However, the apparent Km was 35.9 +/- 3.2 microM for uremic animals, significantly higher (P < or = 0.001) than that of normal rats (16.6 +/- 0.7 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355455 TI - Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes. AB - Sodium retention has been advocated to give rise to hypertension in humans. Increases in blood glucose and insulin concentrations ensue in the stimulation of sodium reabsorption by the kidney. Although the combined occurrence of hyperglycemia and hyperinsulinemia, frequently secondary to insulin resistance with regard to carbohydrate metabolism, is a hallmark of non-insulin dependent diabetes (NIDDM), the role of these abnormalities in determining an impaired natriuresis in NIDDM is not yet fully understood. We studied sodium homeostasis in 14 control subjects and 59 NIDDM normotensive, normoalbuminuric patients who were divided into two groups with markedly impaired (Group 2 NIDDM: 30) and less severely impaired (Group 1 NIDDM: 29) insulin sensitivity during euglycemic hyperinsulinemic (80 to 90 microU/ml plasma insulin) clamp. A hyperglycemic (9 mmol/liter plasma glucose)--nearly euinsulinemic (20 to 40 microU/ml plasma insulin) clamp was also performed in the same 14 controls and in two cohorts of 22 Group 2 and 17 Group 1 NIDDM patients. The two groups of patients had similar overnight fasting glucose levels (Group 1 NIDDM vs. Group 2 NIDDM: 176 +/- 13 vs. 185 +/- 15 mg/dl, mean +/- SE). Conversely, overnight fasting plasma insulin was significantly higher in Group 2 NIDDM than in Group 1 NIDDM patients (Group 1 NIDDM vs. Group 2 NIDDM: 12 +/- 3 vs. 18 +/- 3 microU/ml, P < 0.05). Both NIDDM Groups had higher plasma glucose and insulin than controls (75 +/- 4 mg/dl and 6 +/- 3 microU/ml). Blood pressure levels and albumin excretion rates were slightly but significantly higher in Group 2 NIDDM, but not in Group 1 NIDDM patients, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355456 TI - Stage- and segment-specific expression of cell-adhesion molecules N-CAM, A-CAM, and L-CAM in the kidney. AB - CAM expression was investigated immunohistochemically in tissue sections and in pure cultures of human proximal and distal tubular cells. In the fetal kidney, N CAM immunoreactivity was detected in the non-induced and condensing metanephrogenic mesenchyme, and in all stages until the S-shaped bodies. A-CAM (N cadherin) first appeared in the non-induced mesenchyme and remained present thereafter. Its expression became exclusively associated with the lower limb of the S-shaped bodies and the developing proximal tubule. In contrast, L-CAM (E cadherin; uvomorulin) staining was observed in the fetal collecting duct, the upper limb of the S-shaped bodies, and the developing distal tubule. This segment specific expression of A-CAM and L-CAM in the early developing nephron was maintained in the adult kidney: A-CAM staining was restricted to adherens junctions in the proximal tubule and thin limb, whereas L-CAM was expressed in Bowman's capsule and in all tubular segments except the proximal convoluted and straight tubule. Also after in vitro culture, A-CAM expression was an exclusive property of proximal tubular cells, while L-CAM was confined to distal tubular cells. In conclusion, each major subdivision of the fetal and adult nephron displays a characteristic combination of L-CAM and A-CAM, suggesting that they may be the basis of segmental differentiation and border formation between adjacent nephron segments. PMID- 8355457 TI - Renal osteodystrophy in diabetic patients. AB - To assess the effects of diabetes mellitus on renal osteodystrophy, we examined the database of 256 patients (45% on hemodialysis and 55% on peritoneal dialysis) who were prospectively studied in three Toronto dialysis centers between October of 1987 and 1989. All patients had serial documentation of their clinical, laboratory and risk parameters of bone disease, and completed a series of investigations that included the deferoxamine test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Twenty-five percent of these patients were diabetic. When compared to non-diabetic patients, they were on dialysis for a shorter duration (2.4 +/- 0.3 vs. 4.7 +/- 0.3 years; P < 0.0002), used calcium carbonate as the only phosphate binder more frequently (40 vs. 25%; P < 0.007), and had lower parathyroid hormone levels (12 +/- 1.4 vs. 24 +/- 2.3 pmol/liter; P < 0.002). High-turnover bone disorders (that is, osteitis fibrosa and mixed disorder) were distinctly uncommon (8 vs. 33%; P < 0.01 by Fisher's exact test), while the mild (19 vs. 9%; P = NS) and the aplastic disorders (with mean stainable bone surface aluminum of 6.5 +/- 0.7%) (46 vs. 31%; P = NS) tended to be more common in diabetic patients. The prevalence of aluminum bone disease was the same in both groups (27%). Diabetic patients ingested a smaller cumulative dose of aluminum gels (3.7 +/- 0.6 vs. 9.3 +/- 1.1 kg; P < 0.005), yet had a higher rate of aluminium accumulation on bone surfaces than non-diabetic patients (1.5 +/- 0.19 vs. 0.96 +/- 0.10% per month on dialysis; P < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355458 TI - Role of the renin-angiotensin system on the renal functional reserve in renal transplant recipients. AB - To determine the renal functional reserve in renal transplant recipients, we measured the glomerular filtration rate by inulin clearance and the renal plasma flow by PAH clearance before and during an amino acid infusion (Totamine, 6 to 8 mg/kg/min for 90 to 120 min) in 18 transplanted patients with stable renal function. To test the role of the renin-angiotensin system on the renal functional reserve, we performed a crossover placebo-controlled randomized trial of acute blockade of the renin-angiotensin system by injection of perindoprilat (2 mg i.v.), an inhibitor of angiotensin converting enzyme before amino acid infusion, each patient being studied twice at seven day intervals. Amino acid infusion induced a time-dependent increase in the glomerular filtration rate (P = 0.04), whether or not the renin-angiotensin system was blocked. Maximal increases were from 49.1 +/- 4.1 to 58.9 +/- 5.4, mean +/- SE (18.5%), in control conditions and from 52.4 +/- 5.6 to 62.1 +/- 5.5 ml/min/1.73 m2 (19.7%) after perindoprilat. The increase in glomerular filtration rate was less pronounced in patients taking cyclosporin A than in patients treated with steroid and azathioprine. Amino acid infusion also induced a significant and time-dependent increase (15.2 to 20.2%) in the renal plasma flow (P < 0.01) whether or not perindoprilat had been given. Furthermore, perindoprilat alone increased renal plasma flow by 13.6%, and this effect seemed additive with that of amino acids. Perindoprilat injection decreased filtration fraction (from 0.20 +/- 0.01 to 0.19 +/- 0.01). This parameter returned to basal values after amino acid infusion (0.20 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355459 TI - Parathyroid removal prevents the progression of chronic renal failure induced by high protein diet. AB - The influence of PTH in the progression of renal failure induced by a high protein diet was investigated in either sham operated (SHAM) or parathyroidectomized (PTX) and subtotally nephrectomized (NX) rats. NX-SHAM rats were pair-fed either a high (HPr, 40% casein) or a normal (NPr, 20% casein) protein diet and NX-PTX rats a HPr diet. The results indicate that PTX markedly improved the survival rate and prevented the deterioration of renal function induced by the HPr diet. The number of rats alive after 33 weeks was 0 of 11, 6 of 10, and 9 of 10 in NX-SHAM-HPr, NX-PTX-HPr and NX-SHAM-NPr, respectively. The increases in plasma urea and creatinine were consistently delayed or prevented in NX-PTX as compared to NX-SHAM rats fed the HPr diet. The increment in the mass and calcium content of the kidney remnant induced by HPr was prevented by parathyroidectomy. In addition, PTX completely prevented the rise in the circulating level of cholesterol observed in response to HPr. Normalization of plasma calcium in NX-PTX rats with 1,25-dihydroxyvitamin D3 restored the increment in the renal mass and calcium content and reduced the protective effect of PTX on the progression of renal failure induced by high protein diet. In conclusion, in the subtotal nephrectomized rat model of chronic renal failure, the progression of kidney damage induced by a high protein diet can be prevented by removal of the parathyroid glands. This observation suggests that PTH could be implicated in the mechanism whereby a high protein regimen accelerates the course of chronic renal failure. PMID- 8355460 TI - Effect of erythropoietin therapy and withdrawal on blood coagulation and fibrinolysis in hemodialysis patients. AB - Erythropoietin (EPO) therapy in hemodialysis patients may be associated with an enhanced risk of vascular access and extracorporeal thrombosis. Assessment of blood coagulation and fibrinolysis was performed monthly on a group of 21 hemodialysis patients treated with EPO, and on four iron-deficient hemodialysis patients treated with iron dextran infusions alone. Seventeen of the EPO treated patients were also monitored after withdrawal of EPO to allow hemoglobin to fall to pre-EPO levels, and 16 of these patients during a second subsequent phase of EPO therapy with EPO administered using the alternative route (subcutaneous/intravenous) from the first phase of treatment. Ten untreated hemodialysis patients with intrinsically high hemoglobins were studied as controls. EPO was associated with significant increases in the endothelial product Factor VIII von Willebrand factor antigen (FVIIIvWFAg), and plasma fibrinogen, to levels comparable to those observed in the untreated control patients. Both FVIIIvWFAg and fibrinogen remained significantly elevated when EPO was withdrawn. Whole blood platelet aggregation (spontaneous, collagen, and ADP induced) also increased following EPO, collagen and ADP-induced aggregation, increasing further when EPO was withdrawn. Transient but significant changes occurred in plasma measures of thrombin-antithrombin III complex, prostacyclin stimulating factor, and protein C during the first EPO treatment phase, and also thrombin-antithrombin III complex during the second treatment phase, all favoring a tendency to thrombosis. D-dimer increased significantly following EPO withdrawal. Erythrocyte deformability, and granulocyte aggregation did not change. There was no effect of route of EPO administration (subcutaneous or intravenous) or EPO dose on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355461 TI - Therapeutic efficacy of non-peptide ADH antagonist OPC-31260 in SIADH rats. AB - The present study was undertaken to determine whether the non-peptide V2 antidiuretic hormone (ADH) antagonist 5-dimethylamino-1[4-(2- methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (OPC-31260) normalized hyponatremia in rats with an experimental syndrome of inappropriate secretion of ADH (SIADH). Rats were administered V2 agonist 1-deamino-8-D arginine vasopressin (dDAVP) subcutaneously at a rate of 5 ng/hr using an osmotic minipump and a 40 ml/day liquid diet. Serum sodium levels (SNa) and serum osmolality (SOsm) markedly decreased to 119 mEq/liter and 249 mOsm/kg H2O, respectively, 48 hours after the start of dDAVP administration. Hyponatremia persisted in a similar magnitude during the observation period of 14 days. On days 7 to 13 OPC-31260, administered 5 mg/kg per day orally, promptly raised SNa and SOsm to 134 mEq/liter and 282 mOsm/kg H2O in half a day, respectively, followed by the normalization of SNa and SOsm during the rest of the observation period. The cease of administration of OPC-31260 again decreased SNa and SOsm in rats receiving dDAVP. In contrast, SNa and SOsm were within the normal values in rats receiving 0.15 M NaCl, a vehicle for dDAVP, in the presence or absence of OPC-31260. The administration of OPC-31260 promptly caused marked water diuresis on day 7 in the hyponatremic rats receiving dDAVP, namely 5 mg/kg OPC-31260 markedly increased urinary volume and decreased UOsm. These results indicate that there is dilutional hyponatremia in rats receiving dDAVP and 40 ml/day liquid diets, and that OPC-31260 is an effective therapeutic for hyponatremia associated with dDAVP-induced SIADH. PMID- 8355462 TI - Contributing factors to the inhibition of phagocytosis in hemodialyzed patients. AB - Although polymorphonuclear (PMNL) glucose consumption as an index of metabolic response to phagocytosis in the production of free radical species is depressed in hemodialyzed patients, substantial interindividual differences are registered. Studies evaluating to what variables these differences are related are, however, lacking. In the present study, the relation of several factors to PMNL functional capacity in the breakdown of glucose to CO2 by the hexose monophosphate shunt (HMS) is considered in an individual and multifactorial regression analysis. Starting from a database, collected in 126 stabilized hemodialysis patients, PMNL HMS-response to standard quantities of latex and zymosan was correlated to 14 numerical parameters: time since the start of dialysis, hematocrit, serum creatinine, phosphorus, ferritin, albumin, parathormone, albumin before and after administration of desferrioxamine, residual creatinine clearance, PCR, TACurea, Kt/V and age. In addition, the non-numeric parameters of sex, biocompatibility of dialyzers, and primary diagnosis were also considered. A significant correlation was found for time on dialysis (P < 0.001), hematocrit (P < 0.001), ferritin (P < 0.05), PTH (P < 0.001) and aluminum (P < 0.05). The highest correlation coefficients were found for time on dialysis (latex: N = 126, r = 0.50, P < 0.001; zymosan: N = 126, r = 0.58, P < 0.001). Multivariate correlation analysis of one clinical parameter together with time on dialysis to PMNL response showed that the correlation was strongly weakened or disappeared for ferritin, aluminum and PTH, but not for hematocrit. Our data indicate that time since the start of dialysis is an important, but not unique factor, influencing polymorphonuclear functional capacity in a hemodialysis population. PMID- 8355463 TI - Clonidine, but not bradykinin or ANP, inhibits Na+ and water transport in Dahl SS rat CCD. AB - We examined the actions of potentially natriuretic autacoids in the isolated perfused cortical collecting duct (CCD) dissected from inbred Dahl (Rapp strain) salt-sensitive rats (SS). Atrial natriuretic peptide (ANP, 10 nM), bradykinin (BK, 10 nM), and clonidine (1 microM) were studied to determine their effects on the lumen-to-bath flux of 22Na+ (J1-->b, pmol min-1 mm-1), hydraulic conductivity (Pf, micron/s), and transepithelial voltage (VT, mV). ANP and BK have been shown by others to significantly reduce net Na+ reabsorption and hydraulic conductivity in the Sprague-Dawley (SD) rat CCD, but previous results from our laboratory showed no ANP or BK effect in the SD CCD. In the present study, we were also unable to observe any effect of either ANP or BK in the SS rat CCD. However, in the presence of AVP, clonidine (a partial alpha 2-adrenergic receptor agonist) significantly reduced J1-->b and Pf from 139 +/- 6 (SEM) to 88 +/- 7 and from 959 +/- 176 to 490 +/- 73, respectively. In addition, clonidine significantly depolarized VT from -14.5 +/- 2.8 to -11.2 +/- 1.8. However, unlike its effects in the SD rat CCD, yohimbine (300 nM, an alpha 2-adrenergic receptor antagonist) did not significantly reverse the effects of clonidine on J1-->b, Pf or VT in the SS rat CCD. PMID- 8355464 TI - Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. AB - Endothelins (ET), a group of vasoconstrictor peptides, are expressed in a wide range of tissues and species and bind to specific receptors of which there are at least two subtypes, ETA and ETB. The kidney has been found in animal studies to be highly sensitive to the effects of ET. We have used two new peptide ligands, which are selective for particular ET receptor subtypes (the antagonist BQ123 for ETA and the agonist BQ3020 for ETB) in binding studies to characterize human renal ET receptors. Saturation studies gave equilibrium dissociation constants (Kd) for [I125]ET-1 of 0.17 +/- 0.04 nM and for [I125]BQ3020 of 0.36 +/- 0.06 nM. Hill coefficients were 0.86 +/- 0.03 and 0.77 +/- 0.04, respectively. Macro- and microautoradiography using [I125]-labeled ligands with BQ123 and BQ3020 as competing blockers showed the majority of ET binding to be in the medulla with concentration in the vasa recta bundles, and ETA binding localizing to vascular smooth muscle. The ETB subtype predominated over ETA receptors by about 2:1, and was more generally distributed, with concentration in the collecting system. These findings were confirmed by competition binding assays giving Bmax values (ETB/ETA, fmol/mg protein), for medulla and cortex, respectively, of 18.7 +/- 2.2/11.3 +/- 2.7 and 12.7 +/- 3.9/7.6 +/- 3.5 for BQ3020; and 36.2 +/- 5.6/11.1 +/- 4.1 and 14.9 +/- 1.6/5.3 +/- 0.2 for BQ123. This study establishes ETA and ETB receptor distribution in human kidney and demonstrates that the novel ligands BQ123 and BQ3020 have at least thousand-fold selectivities for the ETA- and ETB receptor subtypes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355465 TI - Interferon-gamma regulation of human renal cortical epithelial cell-derived monocyte chemotactic peptide-1. AB - The chemoattractant signal(s) that results in the transmigration of monocytes/macrophage into the tubulointerstitium during acute inflammation is not known. Monocyte chemotactic peptide-1 (MCP-1), a recently described chemotactic cytokine, may function as both a potent monocyte chemotaxin and activator in renal inflammation. We have studied the proinflammatory conditions in which cultured human renal cortical epithelial cells (RCEC) of tubular origin may be stimulated to produce MCP-1. RCEC were stimulated in a dose-time dependent manner with: IL-1 beta (0.01 to 1.0 ng/ml), TNF (0.1 to 10 ng/ml), LPS (0.1 to 10 micrograms/ml) or INF-gamma (10-1000 U/ml). Conditioned media from RCEC stimulated with either IL-1 beta or INF-gamma produced a monocyte chemoattractant activity which was significantly suppressed with neutralizing antibody to MCP-1. Stimulation of RCEC with either IL-1 beta or INF-gamma resulted in a significant (4- to 5-fold) increase in steady state levels of MCP-1 mRNA. MCP-1 antigenic peptide in RCEC conditioned media was significantly increased over control (2- to 2.5-fold) after stimulation with either IL-1 beta or IFN-gamma. In contrast, production of interleukin-8 (IL-8), a neutrophil chemotactic cytokine, was not stimulated by IFN-gamma in RCEC. Thus, the chemokine signaling repertoire of renal tubule cells may be selectively controlled by IFN-gamma. PMID- 8355466 TI - IFN-gamma mediates stimulation of complement C4 biosynthesis in human proximal tubular epithelial cells. AB - The liver has been presumed to be the main source of complement deposited in inflammatory lesions such as in glomerulonephritis. In a previous study, however, it was demonstrated that renal tubular cells synthesize C3 in vitro. Furthermore, it was shown by others that C4 gene transcripts were detectable in situ in renal tubular cells. Therefore studies were initiated to investigate the synthesis of C4 by proximal tubular epithelial cells (PTEC) in vitro. Biosynthetic labeling experiments showed de novo synthesis of C4 by PTEC. The synthesis of C4 by PTEC and its regulation by IFN-gamma was fully inhibitable by the addition of cycloheximide, indicating that protein synthesis is required for an increase in C4 secretion. Addition of increasing concentrations of IFN-gamma enhanced the production of C4 by PTEC in a dose dependent fashion, with a 2.5-fold maximum. Kinetic experiments demonstrated higher levels of C4 production when stimulated with IFN-gamma for up to 72 hours. The hemolytic activity of C4 present in culture supernatants of PTEC decreased during the culture period as assessed by hemolytic titration. Northern blot analysis showed no enhancement of C4 mRNA in IFN-gamma treated PTEC, indicating that IFN-gamma regulates C4 production at a post-transcriptional level. Antibody blocking experiments confirmed that regulation of C4 production was directly mediated by IFN-gamma. From this study it was concluded that renal cells are able to synthesize complement components that could possibly play a role in inflammatory responses evolving in the kidney. PMID- 8355467 TI - Activation of protein kinase C reduces thromboxane receptors in glomeruli and mesangial cells. AB - The potential role of protein kinase C (PKC) in the modulation of thromboxane A2 (TX) receptor density was evaluated in intact glomeruli and cultured renal mesangial cells (MC) from the rat. Incubation of glomeruli with 0.1 microM phorbol dibutyrate (PDBu) or 30 mM glucose for four hours activated PKC as reflected by increased in situ phosphorylation of the 80 kDa MARCKS protein, a specific endogenous substrate for PKC. High affinity binding to TX receptors, as assessed from the binding of the stable TX antagonist [3H]-Sq-29548 (Sq), was decreased 30% in glomeruli exposed to PDBu and 28% in glomeruli incubated in 30 mM D-glucose for four hours. Concurrent incubation with 0.05 microM of the PKC inhibitor staurosporine blocked both MARCKS protein phosphorylation and the decrease in TX receptor sites in response to either PDBu or 30 mM glucose. Neither 30 mM L-glucose nor 30 mM mannitol altered glomerular PKC activity or TX receptor density, thus excluding an osmotic effect of D-glucose, and implicating cellular metabolism of glucose in the expression of these actions. Inhibition of endogenous production of TX with indomethacin during exposure of glomeruli to 30 mM glucose did not prevent the decrease in TX binding. Homologous down-regulation of TX receptors mediated by endogenous TX was therefore not implicated in this action of glucose. The affinity of the glomerular receptor sites for [3H]-Sq was not affected by PKC activation. MC in passages 3 to 7 also demonstrated high affinity sites for [3H]-Sq (Kd, 2.8 nM). Culture of MC with PDBu (0.05 or 0.1 microM) for four hours decreased TX receptor density.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355468 TI - Shared idiotypes in mesangial deposits in IgA nephropathy are not disease specific. AB - The antigenic specificity of the mesangial IgA in IgA nephropathy (IgAN) remains unknown. Because shared antigenic specificities may be reflected in the usage of shared idiotypes, we prepared five monoclonal anti-idiotypic antibodies (MoAbs) specific for the mesangial IgA eluted from the kidney of an IgAN patient. All five MoAbs reacted with the same idiotype, which proved to be of a public nature. Although the idiotype could be identified in the mesangial deposits of the majority of IgAN patients studied, it was not specific for the disease because it was also found in the glomerular deposits of other types of glomerulonephritis. The idiotype was also expressed in polyethylene glycol precipitates of sera and in pokeweed mitogen-induced plasma cells from both IgAN patients and healthy controls. The conclusion that no disease-specific idiotypes are present in the renal eluate was further supported by the failure to produce polyclonal anti idiotypic antibodies by immunizing a rabbit with the eluted mesangial IgA. Our results support the concept that mesangial IgA deposits in IgAN are of a polyclonal nature. PMID- 8355469 TI - Fish oil in lupus nephritis: clinical findings and methodological implications. AB - Our objective was to determine the effects of fish oil on renal function, symptoms, and serum lipids in patients with lupus nephritis. A double-blind, randomized crossover trial of fish oil versus placebo (olive oil) was done on 26 patients with confirmed systemic lupus; 21 completed the study. Intervention was fish oil or placebo, 15 g/day, for one year followed by a 10 week wash-out period, and then the reverse treatment for one year. At baseline and six month intervals, we measured platelet membrane fatty acids, indices of renal function, a disease activity index, serum lipid levels, blood pressure, serum viscosity and red cell flexibility. We found that platelet membrane phospholipids were uniformly affected by fish oil supplementation (P < 0.001) but with significant carry-over effects despite a 10 week wash-out period. Glomerular filtration rate and serum creatinine were not affected. A non-significant reduction in mean (SE) 24-hour proteinuria occurred, from 1424.1 mg (442.7) on placebo to 896.7 mg (352.2) on fish oil (P = 0.21). Fish oil lowered serum triglycerides from 1.89 (0.25) mmol/liter to 1.02 (0.11) mmol/liter (P = 0.004). VLDL cholesterol decreased markedly whether patients initially received fish oil or placebo (P = 0.004). The size of the reduction was affected by the order of treatment (P = 0.03), but parallel comparisons were significant before the crossover (P = 0.0006). With the possible exception of bleeding time, no other treatment effects were shown with fish oil. However, treatment order effects were seen in urinary IgG excretion (P = 0.03), whole blood viscosity (P < 0.0001), red cell flexibility (P = 0.004), and bleeding time (P = 0.06). In conclusion, one year of dietary supplementation with fish oil in patients with stable lupus nephritis did not improve renal function or reduce disease activity, but did alter some lipid parameters. Hitherto unreported carry-over effects and treatment order effects caused by the olive oil created a risk of type II error, and bear methodologic consideration in the design of future studies. PMID- 8355470 TI - Intra-peritoneal free elastase in CAPD peritonitis. AB - Neutrophil (PMN) recruitment into the peritoneum during acute bacterial peritonitis is an important part of the host defense barrier in CAPD patients. However, the subsequent phagocytosis of bacteria may also lead to PMN degranulation and the release of lysosomal enzymes. We determined the concentration of neutrophil elastase, both in complex with its natural inhibitor alpha 1Pi (E alpha 1Pi), and in uncomplexed, free form, in infected and normal CAPD peritoneal fluid by ELISA. In addition elastase activity was estimated in a casein degradation assay. Infected fluid contained a median (range) of 1.4 nM (0 to 9.2) free elastase by ELISA and 1.2 nM (0 to 11.9) activity. There were strong correlations between the peritoneal leukocyte count and both immunoreactive elastase and activity (r = 0.816, P < 0.001, 0.687, P < 0.01, respectively). In contrast, normal fluid contained 0.0 nM (0 to 0.32) immunoreactive elastase (P < 0.01) and 0.0 nM (0 to 0.6) elastase activity (P < 0.001). E alpha 1Pi complexes were raised significantly during peritonitis at 6.2 nM (0 to 34.3) and were barely detectable in normal fluid 0.0 nM (0 to 0.17; P < 0.005). The study shows that small but significant quantities of uninhibited elastase can be detected in the peritoneal fluid of CAPD patients with acute bacterial peritonitis. This observation may have important implications for the pathogenesis of peritoneal membrane damage and the phlogistic response to infection. PMID- 8355472 TI - Epiphyseal impaction as a cause of severe osteoarticular pain of lower limbs after renal transplantation. AB - A syndrome of severe osteoarticular pain of lower limbs occurring early after renal transplantation (TP) has been recently identified. We describe its prevalence, clinical presentation and outcome. Symptomatic patients have been studied with conventional X-rays, magnetic resonance (MR) imaging, and 99mTechnetium scintigrams of the painful areas. Among 86 patients transplanted over a two-year period, nine (4 men, 5 women; mean age of 40.4 years; range 32 to 59) developed unexplained severe spontaneous osteoarticular pain of lower limbs 19 to 105 (mean 58) days after TP. Pain affected hip(s), knee(s), and/or ankle(s). Clinical examination was usually unremarkable. Favorable outcome was the rule; mean duration of pain was 86 (range 19 to 175) days. Radiographs were abnormal (joint swelling, patchy osteoporosis and/or periosteal reactions) in 41%, MR (epiphyseal fatty marrow replacement by edema and/or hemorrhages) in 83%, and bone scans (one to several epiphyseal foci of increased uptake) in 81% of the symptomatic examined areas. Among joints re-examined 9 to 12 months after resolution of the symptoms, X-rays showed periosteal reactions in 31%, and the bone scans disclosed persistent increased uptake in 53% of the joints, whereas epiphyseal MR abnormalities had completely disappeared in 86%. There was no difference in dialysis duration, post-TP weight gain, evidence of hyperparathyroidism, and steroid and cyclosporine doses between symptomatic and an appropriately selected group of asymptomatic patients. By contrast, serum alkaline phosphatase levels were transiently higher (at the onset of symptoms) in the symptomatic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355471 TI - Role of elevated lecithin: cholesterol acyltransferase and cholesteryl ester transfer protein activities in abnormal lipoproteins from proteinuric patients. AB - Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of free cholesterol, and the distribution of cholesteryl ester among lipoproteins in plasma. Alterations in these processes may play a role in the lipoprotein abnormalities associated with glomerular proteinuria. The activities of LCAT and CETP were measured using excess exogenous substrate assays in nine patients with nephrotic-range proteinuria and in 18 matched controls. The proteinuria-lowering effect of four weeks of angiotensin converting enzyme (ACE) inhibition with enalapril was also studied. Plasma very low lipoprotein and low density lipoprotein (VLDL and LDL) cholesterol, triacylglycerol and apolipoprotein B levels were significantly elevated in the patients compared with controls. High density lipoprotein (HDL) total cholesterol, free cholesterol, cholesteryl ester and the free cholesterol/cholesteryl ester ratio in HDL were lower. Total plasma apolipoprotein A1 was normal. Plasma LCAT and CETP activities were elevated in the patients by 30% (P < 0.01) and by 39% (P < 0.01), respectively, and were both inversely related to serum albumin. VLDL and LDL cholesterol levels were positively related to LCAT and CETP activities, whereas the HDL free cholesterol content was inversely related to LCAT activity. ACE inhibition resulted in a 40% reduction of proteinuria, a partial normalization of LCAT activity, and a decrease in VLDL and LDL cholesterol. In conclusion, elevated activities of LCAT and CETP may provide a mechanism that contributes to the low proportion of cholesterol in HDL relative to that in VLDL and LDL, as well as to the compositional changes of HDL seen in glomerular proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355473 TI - Torsion of the gallbladder in a thirteen year old boy--case report. AB - Torsion of the gallbladder in a child is rare and only 23 cases in children have been reported in Japan. A preoperative diagnosis is very difficult and only four cases have been diagnosed, preoperatively, to date. In the case reported here the suspected preoperative diagnosis was an acute cholecystitis. During the operation, the gallbladder was found to be enlarged to twice the normal size and twisted 540 degrees in a clockwise direction around the cystic duct. A cholecystectomy with abdominal drainage was successfully performed; and the patient was discharged in good condition, 13 days after the operation. It was concluded that one of the most important features for the preoperative diagnosis of torsion of the gallbladder is a dislocation on ultrasonography. PMID- 8355474 TI - Laparoscopic treatment of ectopic pregnancies--reports of two cases. AB - Two cases with ectopic pregnancy were successfully treated by laparoscopic injection of methotrexate (MTX). Case 1: A 29 year-old housewife was laparoscopically treated with a 15 mg MTX injection to the left Fallopian tube. After the laparoscopy, the human chorionic gonadotropin (HCG) was reduced to the normal range. Case 2: A 34 year-old housewife was also laparoscopically treated with a 35 mg MTX injection to the right Fallopian tube. After the laparoscopy, the HCG was quickly reduced to the normal range. The endoscopic approach can be used as the surgical treatment of choice for ectopic pregnancies. PMID- 8355475 TI - Acute obstructive hydrocephalus due to an unruptured basilar bifurcation aneurysm associated with bilateral internal carotid occlusion--a case report. AB - A patient with a higherly positioned and large basilar bifurcation aneurysm associated with bilateral internal carotid occlusion was described. A 63 year-old man was admitted to Yokokura Hospital with disturbed consciousness and mild left hemiparesis. On admission, an initial plain CT-scan showed an acute obstructive hydrocephalus with periventricular lucency caused by an abnormal lesion in the anterior part of the third ventricle. An emergency ventriculo-peritoneal shunt was inserted. The postoperative course was uneventful. The patient regained his consciousness with normal motor function by the following day. Postoperative cerebral angiography disclosed a large basilar bifurcation aneurysm at a higher position, 19 mm from the dorsum sellae. Bilateral internal carotid occlusion had occurred, but rich collateral blood supply from the vertebro-basilar artery via the bilaterally enlarged posterior communicating arteries to the anterior circulation was observed. This rich collateral blood supply to the vertebrobasilar artery might be responsible for the development of the aneurysmal formation due to the increased hemodynamic stress. PMID- 8355476 TI - Increased incidence of cholestasis during total parenteral nutrition in children- factors affecting stone formation. AB - Cholelithiasis is extremely unusual in infants and children. Recently, some cases of cholelithiasis associated with total parenteral nutrition (TPN) have been reported. A group of 400 children receiving TPN were evaluated prospectively for the presence of gallstones and sludge in this report. Eight children (2%) were determined by ultrasonography to have developed cholelithiasis. All of these patients had received large amounts of amino acids (> or = 1.8g/kg/day) and relatively low amounts of fat (< or = 1.7g/kg/day) with a high ratio of non protein: kcal/ml (> 0.8). It was concluded that the administration of large amounts of amino acids and a high ratio of non-protein: kcal/ml enhanced the risk for formation of gallstones and sludge. Conversely, these are prevented by the administration of appropriate amounts of fat. PMID- 8355477 TI - What's in a picture? PMID- 8355478 TI - Two rat isolates of B. Piliformis are different based on protein banding patterns in acrylamide gels and immunoblots. PMID- 8355479 TI - A review of laboratory animal anesthesia with chloral hydrate and chloralose. AB - Chloral hydrate (CH) and alpha-chloralose (CS) are often used to anesthetize laboratory animals although, to our knowledge, there have been no controlled studies of their anesthetic or analgesic effects. Induction of and recovery from anesthesia can be stressful, and anesthesia and analgesic quality have been questioned. Intraperitoneal (i.p.) administration of CH has resulted in adynamic ileus and peritonitis in rats, gastric ulcers in rats, and peritonitis in swine. Light anesthesia is induced in rats. In dogs, CH induces sedation to deep anesthesia when given intravenously. Gastric irritation in dogs can occur when CH is given orally. Chloral hydrate is considered a good sedative-hypnotic for farm animals. Intravenously administered CS anesthetizes dogs and cats for 5 to 10 hours, but the animals may require respiratory support. Chloralose appears to be a satisfactory anesthetic for dogs when stage III thiobarbiturate anesthesia is first induced. It is difficult to gauge the depth of anesthesia and analgesia with CS. In our clinical experience with swine and calves, CH given i.p. leads to adynamic ileus. We have found that CS given i.p. causes an inflammatory response in guinea pigs, rats, and calves. We observed that CS analgesia varies with the type of surgical procedure performed. Based on a literature review and our clinical experience, we suggest that CH or CS anesthesia should be preceded by administration of barbiturates, opioids, alpha-2 agonists, or phenothiazine tranquilizers. Chloral hydrate should only be used as a sedative or hypnotic for dogs; CS should not be used as a sole anesthetic agent. Neither drug should be used i.p. for survival surgery. PMID- 8355480 TI - Pathologic features associated with decreased longevity of mutant sphha/sphha mice with chronic hemolytic anemia: similarities to sequelae of sickle cell anemia in humans. AB - A colony of sphha/sphha mice with congenital hemolytic anemia and an abnormality in erythrocyte spectrin assembly was screened to determine the cause of premature death. Sphha/sphha mice have decreased life span, with 50% of animals dying by 6 months of age. The phenotype of these mutant mice includes moderate anemia (hematocrit: 21 to 28%), reticulocytosis, leukocytosis, lymphocytosis, extensive extramedullary hematopoiesis in spleen and liver, lymph node hyperplasia and membranoproliferative glomerulonephritis. With increased surveillance of this mouse colony, 20 clinically sick anemic mice were evaluated (complete blood counts and cultures of blood), euthanized and necropsied. Compared with anemic mice without clinical signs of disease, sick anemic mice had significantly higher white blood cell counts with only 4 (20%) of 20 animals being severely anemic (hematocrit: 4 to 8%). Blood from 11 (45%) of 20 animals was culture-positive for Pasteurella pneumotropica, Enterococcus, and/or Escherichia coli. In addition to the usual lesions in sphha/sphha mice, sick anemic mice had pneumonitis (95%) with thrombosis and infarction (80%) of one or more organs (spleen, myocardium, pancreas, liver, or bone marrow). The thrombotic tendency that accompanies the chronic hemolytic anemia in sphha/sphha mice, as well as the other clinicopathologic changes in these mutant mice, bears a striking resemblance to some poorly understood sequelae in human patients with sickle cell anemia. This mouse model may be useful in studying the pathophysiology of complications associated with sickle cell anemia in humans. PMID- 8355481 TI - Pharmacokinetics of minocycline and vancomycin in rabbits. AB - The pharmacokinetic disposition of minocycline and vancomycin was studied in New Zealand White rabbits before initiating an experimental staphylococcal endocarditis protocol. Minocycline was administered in a multiple-dose regimen of 3 mg/kg i.v. every 12 h, 3 mg/kg i.v. every 8 h, and 6 mg/kg i.v. every 8 h. Vancomycin was given in a similar fashion using regimens of 75 mg/kg i.v. every 12 h and 50 mg/kg i.v. every 8 h. Multiple serum samples were obtained after the fifth dose and drug concentrations were analyzed by microbiologic assay. The pharmacokinetic parameters for each of the drug regimens were calculated using a two-compartment model by nonlinear least-squares regression. No statistically significant differences were noted in the volume of distribution or the half-life of the individual dosing regimens for either agent. As a result of this study, it appears that a minocycline regimen of 6 mg/kg i.v. every 8 h and a vancomycin regimen of 50 mg/kg i.v. every 8 h are appropriate dosing schemes for a comparative study of these agents in rabbits. PMID- 8355482 TI - Laboratory survival, growth, and digestive gland histologic features of squids reared on living and non-living fish diets. AB - The effects of non-living diets on the survival, growth, and digestive gland histologic features of the bigfin reef squid (Sepioteuthis lessoniana Lesson, 1830) cultured in the laboratory were evaluated during one-half of their life cycle (95 days). Two groups of squids (n = 16 per group) were held in closed seawater systems with similar water volume, temperature, salinity, water filtration, and water flow velocities. Food for the control group consisted of live, freely swimming fish (Cyprinodon variagatus); the test group was trained to grab freshly dead fish (days 1 to 45) and then thawed, frozen fish (days 46 to 95). The two groups were evaluated for differences in (1) food intake, (2) survival, (3) growth (wet weight, mantle length, instantaneous growth rate), (4) morphologic (mantle thickness in four locations, digestive gland weight), and (5) digestive gland histologic features (indices for nuclear density and relative vacuolar density). Unexpectedly, no significant differences were found between the two groups. Mean wet weight increased from 32.1 g to 342.9 g for the control group and from 58.6 g to 372.0 g for the group fed dead food. The results demonstrate that laboratory-cultured squids can survive and grow when fed dead fish (fresh or frozen) as well as live fish without adverse effects on growth, survival, or digestive gland histologic features. PMID- 8355483 TI - Effects of halothane anesthesia on the motility of the sphincter of Oddi and transsphincteric flow in Australian brush-tailed possums. AB - We evaluated the effect of halothane anesthesia on the motility of the sphincter of Oddi and simultaneous transsphincteric flow in Australian Brush-tailed possums (Trichosurus vulpecula). Halothane levels in the range of 0.25 to 2% were administered and decreased transsphincteric flow in a dose-dependent manner. Sphincter of Oddi basal pressure was higher than normal, but not in a dose dependent manner. Additionally, halothane anesthesia influenced the sphincter of Oddi motility by decreasing the motility index (mean amplitude multiplied by frequency of contractions). This decrease was dose dependent. These findings indicate that sphincter of Oddi basal pressure is a major component of sphincter of Oddi motility responsible for regulating transsphincteric flow in this species. For studies of the sphincter of Oddi motility in anesthetized Australian Brush-tailed possums, we recommend anesthetic induction with ketamine (50 mg/kg, i.m.) and the inspired halothane level should not exceed 0.75% during the study period, as the effects we have demonstrated were most evident at levels greater than 0.75%. If higher halothane levels are required to maintain satisfactory anesthesia, an alternative anesthetic agent should be considered. PMID- 8355484 TI - Clinical parameters of the normal baboons (Papio species) and chimpanzees (Pan troglodytes). AB - Improved equipment and advanced progressive techniques by scientists using baboons and chimpanzees in biomedical research have resulted in improved clinical laboratory data. The use of state-of-the-art clinical laboratory instruments, methodologies with improved accuracy, and an increased variety of individual tests routinely requested and performed has necessitated the comparison of current data with prior data produced in our laboratory and with those values reported in the literature. In addition to an expanded hematologic profile, including red blood cell distribution width and mean platelet volume, and a more comprehensive chemical profile of 28 individual tests, additional data collected included values for coagulation profiles, arterial blood gases, serum protein electrophoresis, and urine osmolalities. Samples for evaluation were obtained from clinically normal sedated adult baboons (Papio species) and chimpanzees (Pan troglodytes) and processed conventionally according to Good Laboratory Practice Act standards. Arithmetic means were calculated, values of 3 standard deviations or greater were eliminated, and means were recalculated to include 2 standard deviations. All data correlated well with prior in-house values, and no remarkable differences from established data were detected, thus indicating the reliability of past and present data. Data compared favorably with normal clinical values established for humans. PMID- 8355485 TI - Prophylactic treatment of swine with bretylium for experimental cardiac catheterization. AB - We evaluated a cryothermic ablation catheter for potential use in treating supraventricular tachycardia by cardiac catheterization in miniature swine. Cardiac catheterization was performed on anesthetized miniature swine by using multiple catheters that were inserted bilaterally by either percutaneous or cutdown techniques into the femoral veins. We performed electrophysiologic tests according to standard atrial and ventricular electrical stimulation protocols. Manipulation of catheters in the tricuspid valve area and right ventricle was an essential part of the study. During an initial study of five swine, catheter manipulation produced sustained and nonsustained ventricular tachycardia and ventricular fibrillation. To prevent arrhythmias, bretylium (5 mg/kg) was administered intravenously 10 minutes before catheter manipulation and repeated every 30 minutes throughout the procedure. Since the use of bretylium was instituted, there have been no cases of ventricular fibrillation in a series of 20 animals. We determined that bretylium is effective in the suppression of ventricular arrhythmias in swine undergoing cardiac catheterization. PMID- 8355486 TI - A case of adenomyosis in a pigtailed monkey diagnosed by magnetic resonance imaging and treated with the novel pure antiestrogen, ICI 182,780. PMID- 8355487 TI - Cavernous lymphangioma in a squirrel monkey. PMID- 8355488 TI - Imperforate anus, colo-colic intussusception, and bowel rupture in a neonatal guinea pig. PMID- 8355489 TI - Leptospirosis in a white-lipped tamarin (Saguinus labiatus). PMID- 8355490 TI - Use of medroxyprogesterone acetate to reduce aggression in a male chimpanzee (Pan troglodytes). PMID- 8355491 TI - Chronic epidural implantation of vascular access catheters in the cat lumbosacrum. PMID- 8355492 TI - A reliable method of anesthesia for extensive surgery in small rabbits. PMID- 8355493 TI - Partial splenic resection using nylon cable tie ligatures in rhesus monkeys. PMID- 8355494 TI - Assessing the severity of depressive states in recently detoxified alcoholics. AB - The problem of how to assess "unbiased" symptoms of depression meaningfully in the context of alcoholism bedevils studies of concomitant alcoholism and affective disorder. This study summarizes this controversy and discusses its implications for developing improved measures of depression severity among alcoholics. The Beck Depression Inventory (BDI) responses of 130 alcoholic applicants applying for inpatient care were evaluated using a two-parameter normal item response model. This study demonstrates that a single dimension of depression severity accounts for patient responses well, but that seven BDI items were relatively poor markers of syndrome severity for these alcoholics. The study documents growing consensus among investigators as to which BDI items constitute a fair scale of depression severity among alcoholic patients The availability of "unbiased criteria" for assessing the severity of depression among alcoholics applying for inpatient treatment will enable investigators and clinicians to recognize patients with concomitant alcoholism and affective disorder for special attention and/or treatment. The modified BDI scale proposed here is a candidate for a clinical definition of depression severity among alcoholic patients by virtue of this study's demonstration that it defines a distinct syndrome in this patient sample; but the modified scale must undergo independent tests of validity before its clinical utility can be established. PMID- 8355495 TI - A comparison of functional indexes, derived from screening tests, of chronic alcoholic neurotoxicity in the cerebral cortex, retina and peripheral nervous system. AB - Thirty abstinent alcoholics and 30 age-, education- and occupation-matched normal control subjects were tested with the Category test, the Lanthony-15 test of color discrimination and the Biothesiometer test of vibration detection threshold. Multivariate analysis of covariance revealed significant impairment of the alcoholics on these tasks (p < .007), but univariate analysis revealed that only the Category test yielded a significant difference (p < .001). Canonical correlation analysis, with age and education partialed out, was calculated on the alcoholics' data to determine whether duration, mean and maximum alcohol consumption, age of onset of alcoholism and duration of abstinence predicted performance on the tasks. The prediction was significant (p < .001). Multiple regression analysis revealed that vibration threshold, color preception and Category test performance were decreasingly predicted by the alcohol-related variables (p < .001, .006, .051, respectively). There was no higher incidence of hereditary dyschromatopsia in the alcoholic group than the control group. It was therefore concluded that all three functions (Category test performance, color discrimination, vibrotactile sensitivity) were impaired as a result of alcohol consumption. PMID- 8355496 TI - The correspondence between saliva and breath estimates of blood alcohol concentration: advantages and limitations of the saliva method. AB - Increased awareness of the devastating effects of alcohol misuse on our highways, workplaces and families, as well as on the individual, has resulted in increased social pressure to enforce driving-while-intoxicated laws and to develop educational, prevention and treatment programs. One aspect of this movement is to develop improved sobriety testing to ensure that laws are properly and fairly enforced and that there is compliance with abstinence in treatment. Although sophisticated blood and breath testing devices are available, field tests suggest that saliva alcohol tests based on alcohol-oxidase methodology offer advantages in portability, ease of administration, and cost and time efficiency. We evaluated the validity and reliability of a simple saliva test, based on the enzymatic oxidation of alcohol by alcohol oxidase, for estimating blood alcohol concentration. Ten subjects consumed various doses of alcohol and multiple saliva samples were obtained using alcohol sensitive saliva strips that change color in proportion to the concentration of alcohol. The reflectance values of reacted saliva strips were read by meter and estimates of blood alcohol concentration in the range of 10-90 mg/dl were compared to simultaneous estimates obtained from breath analysis using a Breathalyzer Model 900A. We also examined how alcohol levels changed over time in alcohol reacted saliva strips. The results of regression analysis indicated that the saliva strips and the Breathalyzer gave reasonably close estimates (r = 0.89-.90) of blood alcohol concentration. Correlation coefficents for the values of saliva samples read by meter measured at 10 minutes and at 18 days after collection ranged from .90 to 1.00, showing high test-retest reliability despite storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355497 TI - Alcoholic beverage server liability and the reduction of alcohol-involved problems. AB - Legal liability of alcoholic beverage servers has been suggested as a means to stimulate preventive serving practices and thus reduce alcohol-involved problems. A number of variables contribute (both negatively and positively) to the potential of such liability and a conceptual model that links these variables was developed. In this project, an expert legal panel was used to identify and rate the major legal factors contributing to server liability. As a result each state was ranked according to its relative level of liability exposure. States that ranked highest in server liability were found to have more publicity about such liability, greater awareness and higher concern among licensed establishment owners/managers and different serving practices compared to states with lowest liability exposure. As a result we conclude that server liability has a real potential for reducing alcohol-involved problems but additional research is needed. PMID- 8355498 TI - A cross-study contextual analysis of effects from individual-level drinking and group-level drinking factors: a meta-analysis of multiple longitudinal studies from the collaborative alcohol-related longitudinal project. AB - In contextual (cross-level) analysis within multiple longitudinal general population studies, individual-level drinking behaviors (quantity per typical occasion, frequency of drinking per month and total volume of drinks per month) at final measurement are assessed by three models that simultaneously enter individual- and group-level measures. Two age groups (15-20 and 21-30) are independently assessed. In each model, the Time 1 individual-level drinking behavior and one of three group-level factors are entered. The group-level factors are (1) the percentage of abstainers at Time 1 for each age/sex cohort, (2) the Time 1 group mean for the drinking measure for the age/sex cohort and (3) the mean difference of the age/sex cohort's change in the drinking measure over time. All variables in the model are controlled by variations to exposure in per capita consumption of alcohol during the age/sex cohort's formative years and at Time 2. Meta-analysis assesses the homogeneity of the findings across studies. Models were proposed with the rationale that (1) understanding of individual drinking behavior can be advanced if individual-level data and group-level data are considered in the same models, and (2) integration of these two levels of analyses are, to date, rare. The rationale for using meta-analysis is that findings from the models can be assessed across social contexts with respect to their generalizability. The mean difference model, controlling for individual drinking at Time 1, is the most influential of the group-level models for the younger age group: the degree to which the group changes its drinking pattern is positively related to individual-level drinking behavior at final measurement, over and above the individual's drinking behavior at Time 1, for individual-level frequency of drinking among males (homogeneous among drinkers only). Younger females show more significant relationships for the mean difference females show more significant relationships for the mean difference model. Findings are significant for all relationships examined for the mean difference of the drinking of the group and the individual drinking among the older males and females. Measures of individual-level drinking for all measures at Time 1, controlling for the group-level effects, are significantly related to individual level drinking at final measurement. The results are homogeneous for quantity (drinkers only) and volume among the young. Findings indicate that characterizations of the drinking for both the individual and the group to which the individual belongs predict measures of drinking practices on the individual level over time. PMID- 8355499 TI - The association between fast-flushing response and alcohol use among Japanese Americans. AB - This study investigated the association between the flushing response and alcohol use among Japanese Americans in the greater Los Angeles area. Epidemiolocial data collected through a telephone survey and a mail survey were utilized to test the flushing-alcohol use relationship in the Japanese population, and to explore the effects of socioenvironmental variables. Results showed that, as predicted, those Japanese Americans who exhibited the fast flushing response tended to drink less than those who did not flush, in the general community sample, but the relationship was weaker in the college student sample. Logistic regression analysis identified several covariates that predicted alcohol use among the general community residents: being a male, being single and being of the third/fourth generation. A separate logistic regression analysis with the college students only revealed a moderately significant interaction effect of flushing response and "Greek" affiliation (membership in a campus fraternity or sorority) on alcohol use (i.e., 6 drinks or more in a 24-hour period), indicating that the social context appeared to have a moderating effect on the relationship between the flushing response and alcohol use among Japanese Americans. Eighty out of 300 individuals completely abstained from alcohol consumption and therefore did not know if they possessed the fast-flushing response. Results were discussed with respect to further investigation of the role played by ALDH-I deficiency in varying social situations in the Japanese population. PMID- 8355500 TI - Biases in the perceptions of the consequences of alcohol use among college students. AB - Previous studies have shown that college students' perceptions of the quantity and frequency of peer alcohol consumption are biased. Most students report that their social referents drink more than they themselves do. In the current study members of two fraternities and two sororities (N = 252) were asked to make two types of ratings of alcohol-related consequences across four target individuals. The ratings were: (1) the frequency of occurrence of predefined alcohol-related negative consequences and (2) the degree to which certain alcohol-related consequences are considered "problems." The targets were: themselves, their best friend, a typical member of their fraternity or sorority and a typical student at the university. Estimates of frequency of problem behaviors for typical member of the residence and typical student at the university were significantly higher than ratings for self (p < .001). Data from ratings of behavioral definitions of alcohol problems for the same four targets replicated the bias, although to a lesser degree. Correlational analyses suggest that biased perceptions of problems were unrelated to personal levels of alcohol consumption. Results are discussed in terms of the cognitive and motivational factors that could result in this misrepresentation of peer behavior. PMID- 8355501 TI - Alcohol consumption and work performance. AB - This study examines the work performance of 136 males, including both self reports and reports of workplace collaterals. Comparisons are made on several dimensions of work performance and different levels of alcohol consumption. Different levels of drinking are not associated with scales of self-reported work performance, but relatively heavy drinkers are less frequently absent and late to work than their lighter drinking counterparts. Collateral reports of work performance, however, indicate that heavier drinkers are more likely to score lower on self-direction at work, conflict avoidance at work and interpersonal relations at work. The relationship of alcohol consumption to the technical aspects of work performance is less clear. There is, however, an overall negative relationship between alcohol consumption and technical aspects of work performance as indicated by workplace collateral reports. The implications for the design of workplace intervention programs are considered. PMID- 8355502 TI - Validity of children's reports of parental alcohol abuse. AB - Data from interviews with parents and 9-12 year old children from 303 families were used to test the validity of children's reports of parental alcoholism or problem drinking status. Children's responses to several single-item screening questions that had been used previously to identify children of alcoholics, as well as their responses to the Short Michigan Alcoholism Screening Test for each parent, were compared to parents' alcoholism diagnosis and screening test scores. In general, children's responses correctly identified only a small portion of alcoholic parents and, when all screening items were combined into a single screening tool to increase sensitivity, the false positive rate became unreasonable for most applications. The screening items were better at identifying active alcoholics than abstaining alcoholics but were also better at identifying problem drinking parents than alcoholic parents. None of the screening options tested had optimal characteristics for use in research or intervention applications. PMID- 8355503 TI - Reliability of sibling reports on parental drinking behaviors. AB - Questionnaire data from the Colorado Alcohol Research on Twins and Adoptees (CARTA) were analyzed to explore the reliability of sibling responses to items from the CARTA Family Alcoholism History Questionnaire (FHQ) concerning parental drinking behaviors. Subjects included 142 pairs of male and female, twin and nontwin siblings who reported on paternal and maternal problem drinking. FHQ items were summed to produce drinking-problem scales for fathers and mothers. There was generally good concordance across sibling reports of parental problem drinking symptoms. There was a significant gender difference in that male offspring were more in agreement about their mothers' drinking behavior, while female offspring were more in agreement about their fathers' drinking behavior. For the most part, objective items, such as having two or more drunk-driving arrests, were more reliable (paternal kappa total = .56, maternal = .66) than subjective items, such as being happy only when drinking (paternal = .24, maternal = -.03). This evidence for reliability of sibling reports about parental drinking does seem to validate the use of such questionnaire data in alcohol studies. PMID- 8355504 TI - Severely dependent alcohol abusers may be vulnerable to alcohol cues in television programs. AB - The self-reported ability of 96 alcohol abusers to resist the urge to drink heavily was assessed after they viewed a videotape of a popular prime time television program complete with advertisements. Different versions of the videotape were used to evaluate the effects of a television program with and without alcohol scenes as crossed with the effects of three different types of commercials (i.e., beer, nonalcoholic beverages, food). Before and after viewing the videotape, subjects, who were led to believe that they were participating in two separate and unrelated sets of experimental procedures, completed several drinking questionnaires. Responses to one of the questionnaires provided an unobtrusive measure of self-reported ability to resist the urge to drink heavily. Results indicated that alcohol cues in a television program affected some alcohol abusers' perceived ability to resist the urge to drink heavily. In particular, those with higher alcohol dependence scores showed a decrease in confidence after viewing a television program with alcohol cues compared to subjects who watched the same program but without the alcohol scenes. The clinical implications of these findings are discussed. Until further research is forthcoming, given the artificial nature of the study setting, the results of this study must be viewed with some caution. PMID- 8355505 TI - A randomized phase II trial of low-dose aclarubicin vs very low-dose cytosine arabinoside for treatment of myelodysplastic syndromes. AB - We performed a randomized phase II trial comparing low-dose aclarubicin (LC-ACR) with very low-dose cytosine arabinoside (VLD-AC) in 39 consecutive untreated patients with myelodysplastic syndromes (MDS), including refractory anemia (RA), RA with excess of blasts (RAEB) and RAEB in transformation (RAEB-t). Nineteen patients received the VLD-AC therapy; 2 good responses (GR) and 2 partial responses (PR) were obtained in 11 patients with RAEB and RAEB-t, while 2 PR were obtained in 8 RA patients. Eighteen patients received the LD-ACR therapy; 2 GR and 4 PR were obtained in 11 RAEB/RAEB-t patients while 2 PR in 7 RA patients. There was no significant difference in the therapeutic effects and survival between these two groups of patients. These observations suggest that the LD-ACR therapy is effective in some patients with MDS and can be used as an alternative to the low-dose Ara-C therapy. PMID- 8355506 TI - Human promyelocytic cell line HL60 has the specific binding sites for prolactin and its ornithine decarboxylase, DNA synthesis and cellular proliferation are induced by prolactin. AB - Human prolactin (hPRL) induced ornithine decarboxylase (ODC) activity, subsequently DNA synthesis and cellular proliferation on human promyelocytic cells, HL60, cultured in a serum-free medium. HL60 cells had 2100 specific binding sites for hPRL per cell, showing a dissociation constant of 1.1 x 10(-10) M. Binding of 125I-PRL to the cells was not blocked by simultaneous addition of human growth hormone. ODC activity and DNA synthesis were activated maximally at 5 and 20 h, respectively, after the addition of 0.05 nM hPRL. These effects of PRL on cellular proliferation, ODC activity and DNA synthesis were abolished by the simultaneous addition of anti-hPRL antibody. Simultaneous addition of an irreversible inhibitor of ODC, difluoromethyl ornithine (DFMO), also abolished the inductions of ODC and DNA synthesis by hPRL. The inhibitory effect of DFMO on hPRL-induced DNA synthesis was reversed by the addition of putrescine to the culture medium. These results suggest that hPRL binds to the prolactin receptor on HL60 cells and induces ODC activity to increase cellular polyamine levels, which eventually stimulates DNA synthesis and cellular proliferation. PMID- 8355507 TI - Expression of differentially phosphorylated Rb and mutant p53 proteins in myeloid leukemia cell lines. AB - We studied the structure and expression of Rb and p53 genes in six myeloid leukemia cell lines (HL-60, KBM3, K562, KBM5, EM2, KBM7) in the light of the published reports that structural abnormalities of these genes are rarely seen in leukemic cells and also a recent finding that Rb gene expression can be regulated by the p53 protein. Except for HL-60 cells which have a truncated p53 gene, none of the other cell lines revealed any gross structural abnormalities in the Rb and p53 genes. KBM3, KBM5 and EM-2 expressed lower levels of Rb mRNA than HL-60, K562 and KBM7. The amount of Rb protein was lowest in KBM3 cells and in this and two other cell lines (KBM5, KBM7) Rb was markedly hypophosphorylated compared to the other three cell lines. HL-60 and K562 did not express p53 m-RNA, while the other four cell lines all expressed high levels of mutant p53 protein. Thus even in the absence of gross structural alterations, subtle abnormalities in the expression pattern of Rb and p53 genes occur in myeloid leukemia cells. PMID- 8355508 TI - Thermal stress as an inducer of differentiation of U937 cells. AB - The individual and combined effects of heat shock, all-trans retinoic acid and 1,25-dihydroxyvitamin D3 on inhibition of cell growth and initiation of differentiation were investigated on U937 human leukemia cells. Incubation of U937 cells at 43 degrees C for 1 h did not affect cell viability but induced a reduction of cell growth and the emergence of a differentiated phenotype, characterized by the acquisition of chemiluminescent responses to various oxidative burst inducers and by the capacity to produce IL-6 in response to bacterial lipopolysaccharide. Heat shock alone, therefore, appears to be an efficient inducer of cell differentiation. In addition, heat shock primed the cells to respond more efficiently to the action of retinoic acid and vitamin D, and amplified the phenotypic changes initiated by pretreatment of U937 cells with these agents. PMID- 8355509 TI - Phorbol ester induction of early response gene expression in lymphocytic leukemia and normal human B-cells. AB - The spectrum of early response genes induced following phorbol ester (phorbol 12 myristate 13-acetate-PMA) stimulation of B-chronic lymphocytic leukemia cells was compared with that in normal tonsillar B-cells by using a panel of 20 gene probes. Of these, 2 (fos-B and Fra-1) were not expressed in either cell type; 11 displayed a comparable pattern and magnitude of induction in both the cell types, and one anonymous gene (5L3) that was inducible in leukemic cells was not detectably expressed in normal B-cells. Four further anonymous cDNAs (1R21, 10A, 1R19 and 3L11) detected transcripts that were constitutively expressed in normal B-cells with a concomitant reduction in inducibility compared with leukemic B cells, whilst jun-B and jun-D, which were both inducible in normal B-cells, were constitutively expressed and only marginally PMA-inducible in leukemic B-cells. These data demonstrate clear differences in the PMA-activated early response gene regulatory pathways between normal and lymphocytic leukemia B-cells, which may reflect perturbations in signal transduction pathways that manifest in the differentiation arrest characteristic of these malignant B-cells. PMID- 8355510 TI - Decreased blood flow to rat bone marrow, bone, spleen, and liver in acute leukemia. AB - An acute promyelocytic leukemia in the rat (BNML) has been used in model studies on pathogenesis and therapy of human acute myeloid leukemia. The blood supply to bone marrow during BNML development has hitherto not been examined, even though in general, blood flow to hematopoietic tissues might affect drug treatment and marrow transplantation regimes. We measured the perfusion of various organs during the course of the disease in untreated rats and in rats given one injection of cyclophosphamide treatment. Organ perfusion was measured with radioactive microspheres. Blood flow per gram tissue to the bone marrow, bone, spleen, and liver declined gradually during the leukemic progression, thus paralleling the growth of leukemic deposits. Cyclophosphamide treatment retarded, but did not reverse, the decreasing perfusion of these tissues. PMID- 8355511 TI - Immunophenotypic and idiotypic characterisation of the leukaemic B-cells from patients with prolymphocytic leukaemia: evidence for a selective expression of immunoglobulin variable region (IGV) gene products. AB - B-cell prolymphocytic leukaemia (B-PLL) is a rare chronic lymphoproliferative disease characterised by a massive splenomegaly associated with a mild or no lymphadenopathy and a high leukocyte count, mostly representing prolymphocytic features. We have studied membrane expression of certain Ig VK and VH gene products in five patients with B-PLL using a panel of monoclonal anti-subgroup and anti-cross-reactive idiotype (CRI) antibodies. Membrane expression of leukocyte-associated markers has also been investigated. The leukaemic cells from four patients expressed VKIII and VKIIIb subgroup and sub-subgroup kappa light chains. The VKIIIb and VHI-associated CRI identified by the monoclonal antibodies (MoAb) 17-109 and G8 were co-expressed in one patient. No B-cells from the patients expressed the VHIII-associated CRI. The same pattern of CRI expression was observed in a serum paraprotein collected from one of the patients. These results suggest a biased selection for the IG VKIII and VKIIIb light chains in B PLL. PMID- 8355512 TI - Minimal residual disease status in pre-B acute lymphoblastic leukemia patients after chemotherapy and bone marrow transplantation: assessment of the anti leukemic effects of chemotherapy and BMT. AB - We prospectively analyzed minimal residual disease (MRD) in four patients with B cell precursor acute lymphoblastic leukemia who had been in complete remission for more than one year after chemotherapy and allogenic or autologous bone marrow transplantation (BMT). MRD was quantitatively estimated using polymerase chain reaction amplification to detect the complementarity-determining region III of the immunoglobulin heavy chain gene at limiting dilution DNA samples. Our study showed that remission induction chemotherapy reduced at most 2-logs of leukemia cells, and that subsequent consolidation chemotherapy induced further reduction of leukemia cells. In two cases, 10(-5) levels of MRD were detected two months after BMT. However, no MRD was detected four months after BMT. We also showed the effectiveness of ex vivo purging with anti-CALLA monoclonal antibodies which eliminated at least 2-logs of leukemia cells in autologous BMT. Our results suggest that this detection system is useful for assessing the reduction of the original leukemia clone, and that the presence of MRD within three months after BMT is not related to clinical outcome. PMID- 8355514 TI - Unbalanced translocation (1;7) and inversion 16 in a patient with acute myelocytic leukemia. AB - Pericentric inversion of chromosome 16 has been delineated as a characteristic chromosome abnormality of acute myelomonocytic leukemia with abnormal eosinophils and a favorable prognosis. By contrast, unbalanced translocation (1;7) has been reported as frequently associated with therapy-related leukemia, and patients with this karyotypic abnormality are susceptible to severe infections which lead to a poor prognosis. Here we report the first case of acute myelocytic leukemia in which the complexed chromosomal aberrations of der(7)t(1;7)(cen;cen) and inv(16) were found simultaneously in the patient's leukemia cells. Eosinocytosis has not been observed so far, but life-threatening pneumonia developed during the remission induction therapy. PMID- 8355513 TI - Prediction of chemotherapy response in human leukemia using in vitro chemosensitivity test. AB - We performed the dye exclusion assay (DEA) and the MTT dye reduction assay to determine the drug sensitivity of acute leukemia using short-term microplate cultures. The in vitro results were compared with the clinical response of 31 patients with acute leukemia treated by combination chemotherapy. The true positive rates of the DEA and MTT assays were 86.7 and 91.3%, respectively; the true-negative rates were 33.3 and 77.8%, respectively; and the predictive accuracy was 62.5 and 87.5%, respectively. The DEA and MTT assays gave comparable results in drug sensitivity testing of leukemic blast cells. Our data suggest that MTT assay is the more suitable for assessing chemosensitivity in acute leukemia. PMID- 8355515 TI - Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha 2C and low-dose cytosine arabinoside. AB - Patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) and on interferon (IFN)-alpha-2c treatment for at least two months were entered in the present pilot study. IFN-alpha treatment was maintained identically and cytosine arabinoside (Ara-C) was added at monthly cycles of 10 mg/m2/day for ten days subcutaneously. In the case of a leukocyte nadir above 10 G/l, the Ara-C dose was increased to 20 mg/m2/day for 10 days per month. Ten of the eleven patients entered in this study were evaluable for toxicity and response. They received a total of 87 IFN-alpha/Ara-C cycles (3-14/patient). Five patients received 1-5 cycles with Ara-C dose intensification to 20 mg/m2/day. The following gastrointestinal and hematological toxicities were attributable to Ara C, as they had not been observed in these patients during the preceding IFN-alpha monotherapy period. Gastrointestinal side effects consisted of nausea grade 1 (n = 5) and diarrhea grade 2 (n = 1). Hematotoxicity was observed in eight patients, grade 1 in five patients and grades 2, 3 and 4 in one of the patients each. Both episodes of grades 3 and 4 toxicity were seen during dose escalation to 20 mg/m2. Small cytogenetic responses (4-14%) were observed in 3 patients and a larger one (50%) in one patient, hematological improvement or stable disease in an additional three patients. These preliminary data suggest that the combination of IFN-alpha and low-dose Ara-C is active in inducing cytogenetic responses in CML patients at an acceptable rate of toxicity and therefore warrant further investigation. PMID- 8355516 TI - Isochromosome 17q as a sole anomaly: a distinct myelodysplastic syndrome entity? AB - We report four patients with myelodysplastic syndrome (MDS) with isochromosome i(17q) as the sole chromosomal anomaly. One patient was classified as refractory anemia (RA) and three as refractory anemia with excess of blasts (RAEB). All four patients shared several features such as male sex, advanced age, severe anemia, as well as a bone marrow with myeloproliferative characteristics: hypercellularity, prominent baso- and eosinophilia, and marked increase of micromegakaryocytes. We suggest that patients with i(17q) as the sole chromosomal anomaly may identify a distinct MDS with characteristics between MDS and chronic myeloproliferative disorders (CMPD). PMID- 8355517 TI - Rearrangement of the N-myc oncogene in acute leukemias: a case report. AB - Rearrangements of the N-myc oncogene have not been described in the literature. The authors present a case of ANLL with the N-myc gene rearranged out of 16 ANLLs and 11 ALLs. While the proportion of the blast cells in the case reported was 85%, the rearranged gene gave a hybridization band which was less intense than that of the germline band, making it probable that this gene rearrangement is present in a leukemia subclone. The c-myc oncogene as well as Ig and TcR genes were in germline configurations. The presence of the rearranged N-myc in the reported case could imply an alternative mechanism of mutation of this oncogene in the pathogenesis of hematological malignancies. PMID- 8355518 TI - Estimation of lymph flow by relating lymphatic pump function to passive flow curves. AB - Active pumping in postnodal lymphatic vessels is an important factor influencing lymph flow. However, the output of the lymphatic pump also depends on the rate of flow into the pump. This arrangement is similar to the blood circulation where cardiac output depends on the rate of blood flow through the veins into the heart (venous return) and on the pumping characteristics of the heart itself (cardiac function curves). One common way to analyze the blood circulation rate is to interrelate venous return and cardiac function curves. In this study, we used a similar technique to analyze lymph flow. We used lymphatic flow vs. outflow pressure (passive flow) relationships for nonpumping lymphatics to represent the inflow of lymph to the lymphatic pump. We used data on the pumping characteristics of postnodal lymphatic vessels to generate relationships between lymphatic pump outflow and pump inflow pressure (pump function curves), and then interrelated these curves. The results were not only similar to previously measured lymph flow data obtained from experimental animals, but also support the observation that under normal circumstances lymph flow is periodic and in surges (active pumping) but in edematogenic states lymph flows more continuously (i.e., passively). PMID- 8355519 TI - Disorders of the intestinal mesenteric lymphatic system. AB - Disorders of the intestinal lymphatic transport system are rare and typically associated with protein losing enteropathy (PLE). Hypoproteinemia caused by intestinal lymphangiectasia is often associated with lymphedema of the legs and occasionally with chyluria, chylometrorrhea and chylous ascites. This article examines the varied presentations of lymphangiectasia syndromes including its pathophysiology. Diagnosis is based on signs and symptoms, specific laboratory findings, and confirmed by contrast small bowel series, lymphography and best of all laparoscopy. We describe 12 patients with PLE secondary to primary intestinal lymphangiectasia (1980-1991). Treatment was non-operative (dietary) in 8 patients and surgical in 4 including segmental resections of the jejunum in two, lymphatic mesenteric venous anastomosis in one, and peritoneal-venous (LeVeen) shunt in one with overall satisfactory results. PMID- 8355520 TI - Terminal endothelial cells of lymph capillaries as active transport structures involved in the formation of lymph in rat skin. AB - Electron microscopic examination of lymph capillaries of the dermal papillae of rat scalp skin revealed continuous extension of the lymph collection system into 4 to 10 micron diameter lumen capillaries with thin walls, scant basement lamellae (membranes), and blind-endings of 1 to 4 micron lumen diameter within endothelial-type cells. These terminal endothelial cells also displayed intracytoplasmic channels and pinocytotic vesicles, extensive cytoplasmic processes and a high cytoplasmic volume-percent of mitochondria suggesting active transport capabilities of lymphatic endothelia. The mitochondrial cytoplasmic volume-percent (mean 14.5%) exceeded that present in blood capillary endothelial cells of the rat brain (the anatomic substrate of the blood-brain barrier), that have a volume-percent of mitochondria of 10 to 12% (1). Active transport processes centered in such endothelial cells could account for a portion of lymph formation, and explain the continued accumulation of lymphedema distal to blocked lymphatic collection ducts when lymphatic intraluminal pressure is greatly increased. The small lumen diameter capillaries, which correspond spatially to the prelymphatics of other authors (2), typically converge in groups of three to form larger diameter lymph capillaries corresponding to the lymph "initials" previously described (2,3). PMID- 8355521 TI - Endothelial transdifferentiated phenotype and cell-cycle kinetics of AIDS associated Kaposi sarcoma cells. AB - The nature of Kaposi sarcoma (KS) (vascular malignancy vs. discordant angiogenesis) and lineage of the progenitor cell remain unclear. Therefore, AIDS KS enzyme isolate cultures were prepared from excised skin lesions. Endothelial marker positivity for Factor VIII related antigen (F8RAg), Ulex europaeus agglutinin (UEA), and angiotensin-converting enzyme (ACE) were determined by fluorescence microscopy (FM) and flow cytometry (FCM). DNA cell-cycle analysis was performed using FCM. KS lesions showed large thick-walled channels (F8RAg and UEA strongly +), narrow vascular slits and thin-walled lakes (F8RAg and UEA weakly +), and non-prominent spindle cells (F8RAg and UEA almost uniformly negative). KS cultures yielded heterogenous populations of spindle, stellate, and flattened endothelial-like cells, displaying positivity for F8RAg (64 +/- 3%; mean +/- SE), UEA (40 +/- 9%), and ACE (81 +/- 9%). When injected subcutaneously in the nude mouse these cells failed to produce tumors. During contact inhibition induced quiescence, KS cultures exhibited a high G2M (18 +/- 3%) compared to non KS (7 +/- 4%; p < 0.04), evidence of an altered proliferative potential consistent with a transdifferentiated or transformed phenotype. PMID- 8355522 TI - Morpho-physiological function and role of omental milky spots as omentum associated lymphoid tissue (OALT) in the peritoneal cavity. AB - The morpho-physiological function and role of milky spots in the greater omentum are reviewed. These milky spots are composed of cellular aggregations of mesenchymal cells, mainly macrophages and lymphocytes, surrounding capillary convolutions termed omental glomeruli. Initial lymphatics of the omentum begin at the milky spots and drain into lymph collectors. The lymphatic capillaries in the omental milky spots take part in the absorption of various substances from the peritoneal cavity. Omental milky spots probably act as the first line of defense in the peritoneal cavity and therefore are immunologically important. In human infants, most of the cells in these milky spots are macrophages (49%); less common are B lymphocytes (29%) and T lymphocytes (12%). Whereas macrophages form clusters near the peritoneal surface of the milky spots and are oriented toward the peritoneal cavity for migration, clusters of B and T lymphocytes are typically found in periarteriolar locations within the milky spots. This cell zonation facilitates phagocytosis and processing of circulating antigens and foreign bodies which emanate from the peritoneal cavity. During inflammation, the number and size of omental milky spots dramatically increase, and some develop germinal centers within the lymphatic follicles and produce antibodies. During intraperitoneal immunotherapy, the omental milky spots and their cellular elements may be activated by intraperitoneal administration of biological response modifiers, and thereby represent an important immunoregulatory system for the peritoneal cavity. Omental milky spots are also closely linked to the dissemination of cancer cells. Thus, intraperitoneally inoculated experimental tumor cells selectively invade the milky spots and proliferate there to form tumor nodules. This occurrence is relevant to clinical practice where nodular metastases to the omentum are common. Omental milky spots are analogous to regional lymph nodes and as such are the omentum-associated lymphoid tissues and participate in intraperitoneal immune reactions. PMID- 8355523 TI - [The evolution of the Spanish health system]. PMID- 8355524 TI - [The image of the family physician]. PMID- 8355525 TI - [Euthanasia, yes; euthanasia, no]. PMID- 8355526 TI - [Capacity, equality, and life expectancy]. PMID- 8355527 TI - [To what extent can pollution affect our health?]. PMID- 8355528 TI - [Stress]. PMID- 8355529 TI - [The teaching of medicine, should the model be changed?]. PMID- 8355530 TI - [The transplantation age]. PMID- 8355531 TI - [HIV infection. When will the cure be found?]. PMID- 8355532 TI - [Ambulatory major surgery: an alternative to traditional surgery?]. PMID- 8355533 TI - [Teleinformation in medicine, where is it heading to?]. PMID- 8355534 TI - [Artificial intelligence in medicine. Current status and perspectives]. PMID- 8355535 TI - [The future of diagnostic aids in medicine]. PMID- 8355536 TI - [The human genome project: reality and hope]. PMID- 8355537 TI - [Financing medical research]. PMID- 8355538 TI - [The way the ideal hospital should be]. PMID- 8355539 TI - [Clinical usefulness of adrenal gland computed tomography in the etiologic diagnosis of Addison's disease]. AB - BACKGROUND: The aim of this study was to evaluate adrenal gland morphology by computerized tomography (CT) in the etiologic diagnosis of Addison's disease. METHODS: Twenty-two patients were grouped according to their etiology based on the study of antiadrenal antibodies at diagnosis of the disease: 7 were positive (autoimmune etiology or EAA), 11 were negative (tuberculous etiology or EAT) and in four serologic study was not available (undetermined etiology or EAI). Adrenal gland CT was performed with contiguous sections every 5 mm. In eight cases the examination was carried out upon diagnosis of the disease (initial stage) and in 14 between 2 and 17 years following diagnosis (evolutive stage). RESULTS: In all the patients of the EAA group, examined in either the initial or evolutive stages, the adrenal glands appeared atrophic without calcifications. In the patients of the EAT group adrenal masses of proven tuberculous origin were found in five who were studied in the initial stage and with atrophic glands with calcifications in the remaining patients examined in the evolutive stage, with the exception of two cases with atrophic adrenal glands without calcifications which could serologically be considered as false negatives having autoimmune etiology. The patients in the EAI groups were studied in the evolutive stage with three having atrophic glands with calcifications and one atrophic adrenal glands without calcifications. CONCLUSIONS: Adrenal gland computerized tomography is an useful examination to differentiate between autoimmune or tuberculous origin in Addison's disease. Clinical application may be justified in all patients of recent diagnosis when the study of the antiadrenal antibodies is negative or not possible. PMID- 8355540 TI - [Inhalation chambers: an alternative to the conventional inhalator?]. AB - BACKGROUND: Aerosol inhalers constitute the most commonly used form of administration of medication by most of the patients with respiratory disease although incorrect usage is a demonstrated fact in many studies. A previous study demonstrated that, despite correct instruction by health care staff and the patients, 30% of the same use these inhalers incorrectly. In the present study, the efficacy of inhalation chambers (750 ml) and spacers (50 ml) versus the conventional inhaler was evaluated by quantification of bronchodilator response. METHODS: Fifty-six stable patients with chronic obstruction to air flow in habitual treatment with aerosol inhalers (AI) were studied. For this study 27 patients used the chamber and 29 the spacer. The patients using the maneuvers correctly (n = 42) and those that did not (n = 14) were studied together and separately. RESULTS: Patients using the inhaler incorrectly were found to benefit significantly from either of the procedures. Upon comparison of the chambers (750 ml) with the spacers (50 ml) a significant improvement was observed with the former. CONCLUSIONS: The response to bronchodilator treatment in patients not using aerosol inhalers correctly improves significantly upon use of either inhalation chambers or spacers with the former demonstrating the best results. PMID- 8355541 TI - [The effect of continuous positive pressure in the nasal airway on the right ventricular function in obstructive apnea sleep syndrome]. AB - BACKGROUND: The aim of this study was to evaluate the right ventricular function in the obstructive apnea sleep syndrome (OSAS) and to determine the effect of the continuous use of a continuous positive pressure nasal device on the airway (CPSPn) produces on this aspect of the disease. METHODS: Forty patients were diagnosed of OSAS by study of spontaneous night sleep. A functional respiratory study was performed in all the patients as was a calculation of the index of body mass (IBM) and isotopic ventriculography for the calculation of the right and left ventricular ejection fractions (RVEF and LVEF). Twenty-six patients were followed after 8.4 +/- 3.3 months of home treatment with CPAPn in which these studies were repeated. RESULTS: Twenty-four of the 40 patients (60%) had RVEF lower than 0.45. These 24 patients had paO2 in vigil state (69.9 +/- 13.6 mmHg) than those with a normal RVEF (80.1 +/- 8.7 mmHg) (p < 0.05). After treatment with CPAPn an elevation was observed in the RVEF in the group which was followed. This increase was significant in the subgroup sharing low RVEF (n = 16) prior to starting treatment upon passing from 0.39 (+/- 0.02) to 0.45 (+/- 0.04) (p < 0.001). CONCLUSIONS: Right ventricular dysfunction in frequent in patients with the obstructive apnea sleep syndrome and is more frequent in patients maintaining hypoxemia in vigil. The continual use of continuous positive pressure in the nasal airway produces improvement in right ventricular function particularly in those in whom this was most disturbed. PMID- 8355542 TI - [Information needs of the health professional. Available resources and ways of access]. PMID- 8355543 TI - [New diagnostic and therapeutic aspects of hyper-IgE syndrome. Report of 3 cases]. AB - Three female patients, 46, 34, and 19 years old, diagnosed of hyper-IgE syndrome are reported. The most relevant clinical findings are recurrent sinopulmonary tract infections, cold staphylococcal abscesses and chronic dermatitis. All patients presented elevated serum IgE levels (> 3,000 U/ml) and blood eosinophilia (> 0.6 x 10(9) cel/l). Two patients presented impaired antibody forming capacity to tetanus and pneumococcal antigens; one of these patients also had low serum IgG2 levels. After initiation of the intravenous gammaglobulin therapy, a marked improvement of infectious problems was observed. The controversial pathophysiology of this syndrome, the antibody deficiency present in some patients and the rationale for intravenous gammaglobulin therapy are discussed. PMID- 8355544 TI - [New techniques for nucleic acid amplification]. PMID- 8355545 TI - [The world of serotonin and its receptors. Physiopathologic, clinical, and therapeutic aspects]. PMID- 8355546 TI - [Reiter's syndrome and IgA glomerulonephritis]. PMID- 8355547 TI - [Acute pancreatitis in acute poisoning caused by organophosphate insecticides. Report of 3 cases]. PMID- 8355548 TI - [Acute hemolysis and dermonecrosis secondary to bite of Loxosceles (brown spider)]. PMID- 8355549 TI - [Bronchoalveolar lavage and diffusion capacity of carbon monoxide in the diagnosis of diffuse alveolar hemorrhage]. PMID- 8355550 TI - [The Fisher's test]. PMID- 8355551 TI - [Hyperthyroidism secondary to interferon therapy]. PMID- 8355552 TI - [Campylobacter jejuni sepsis and chronic terminal kidney insufficiency]. PMID- 8355553 TI - [Treatment with thalidomide and production of tumor necrosis factor alpha]. PMID- 8355554 TI - Endothelin peptides: biological actions and pathophysiological significance in the lung. AB - Endothelins (ETs) are a family of novel regulatory peptides. Besides their effects on the cardiovascular system, which have been extensively described, several lines of evidence suggest an important role for ETs in regulating pulmonary functions. ETs are present in the pulmonary tissues, bronchoalveolar space and pulmonary circulation. Release of ETs from macrophages, endothelial and epithelial cells is modulated by a variety of chemical and physical stimuli and is regulated at the level of transcription or translation. Specific endothelin receptors have been identified in the airways as well as in the pulmonary vasculature. ETs are among the most potent bronchoconstrictors yet described. In the pulmonary circulation, ETs can elicit both vasodilation and vasoconstriction and can enhance vascular permeability. ETs could also modulate activation of inflammatory cells. Enhanced ET expression and/or production have been detected in asthma, certain pulmonary tumors, shock states associated with adult respiratory distress syndrome and pulmonary hypertension. These findings suggest that by regulating pulmonary vascular and airway tone, activation of inflammatory cells and cellular growth and/or differentiation, ETs may play an important role in pulmonary pathophysiology. PMID- 8355555 TI - Reversal of activity profile in analogs of the antiprogestin RU 486: effect of a 16 alpha-substituent on progestational (agonist) activity. AB - 16 alpha-Ethyl-17 beta-acetyl substitution in the D-ring of steroids having an 11 beta-aryl-4,9-dien-3-one structure resulted in compounds with strong progestational activity. These compounds caused endometrial proliferation in the uterus of estrogen-primed rabbits with a potency greater than that of progesterone and had no detectable antiprogestational activity in this model. This is in stark contrast with the marked antiprogestational activity in rabbits, rats and humans reported for most 11 beta-aryl-4,9-diene-3-keto steroids such as RU 486 and its 17 beta-acetyl-17 alpha-acetoxy analog, 17 alpha-acetoxy-11 beta (4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene- 3,20-dione. Examination of structure activity relationships in combination with computer aided molecular modelling suggests that a binding interaction of the 16 alpha-ethyl group with the progesterone receptor (PR) or the PR-progestin response element complex may play the major role in this reversal of activity profile. PMID- 8355556 TI - Metabolism of benzo(a)pyrene by lung microsomes from rabbits pretreated with polychlorinated biphenyls and 2,3,4,7,8-pentachlorodibenzofuran. AB - The polychlorinated biphenyls (PCBs) mixture, Aroclor 1254, is a weak inducer of aryl hydrocarbon hydroxylase (AHH) activity in rabbit lung. In contrast, 2,3,4,7,8-pentachlorodibenzofuran (PCDF), like 3-methylcholanthrene (3-MC), caused a 3-fold increase in pulmonary AHH activity. An important finding of the present studies was that AHH activity, whether assayed by the flourometric or HPLC methods, was dependent on the buffer used in the incubation mixture. The metabolism of benzo(a)pyrene (BP) to its oxidative metabolites, as assayed by HPLC, revealed that PCBs, PCDF and 3-MC pretreatments caused greater than 15-fold and about 3- to 4-fold increase in the formation of the tumorigenic metabolites 9,10- and 7,8-dihydrodiols, respectively. In contrast to 3-MC and PCDF, PCBs caused a 75% decrease in the formation of the K-region metabolite, BP-4,5 dihydrodiol. These studies strongly suggest that the catalysis of BP metabolism is mediated by more than one isoform of cytochrome P450 (P450). PMID- 8355557 TI - Adjuvant use of warm butyl alcohol vapor in experimental pulmonary edema. AB - Studies were done to determine if warm n-butyl alcohol vapor might be effective for the destruction of respiratory tract foam bubbles and for alleviation of the arterial hypoxemia accompanying severe acute pulmonary edema. In vitro studies showed that warm butyl alcohol vapors made from 5% and 7% butyl alcohol solutions at 39 degrees C were much more effective in antifoam activity against synthetic foam bubbles than ethyl alcohol vapors, made from 20% and 30% ethyl alcohol at 22 degrees C. Warm butyl alcohol vapor also slowly destroyed in vitro the fine foam bubbles of alveolar lining origin made in rabbit lung post mortem. Evolving lung edema was induced in anesthetized rabbits by aspiration of 1.1 ml/kg of 1.2 molal sorbitol/0.14 molal sodium chloride/0.01 molal hydrochloric acid solution of pH 2.0. After established severe arterial hypoxemia and in the absence of overt foam, inhalation of warm butyl alcohol/H2O vapor-air mixture, made by air humidification from 7% butyl alcohol at 39 degrees C, alleviated promptly the hypoxemia. The improvement was progressive over the first 45 minutes of continued vapor therapy. The lessened hypoxemia occurred without concurrent improvement in the amount of formed lung edema fluid. Control inhalations of warm 100% H2O vapor air mixture did not improve the hypoxemia. The only noted side effects of warm butyl alcohol vapor treatments were slight hypotension and slight metabolic acidosis which developed very slowly. The results suggest that warm butyl alcohol vapor might prove to be an effective adjuvant agent to lessen critically severe hypoxemia in selective cases of acute pulmonary edema in man. PMID- 8355558 TI - The effect of propylene glycol on the P450-dependent metabolism of acetaminophen and other chemicals in subcellular fractions of mouse liver. AB - Propylene glycol (PG) decreases the hepatotoxicity of acetaminophen (APAP). To elucidate the mechanism for this response, we measured the effect of PG on the in vitro metabolism of APAP by subcellular liver fractions from 6-10 week-old male B6C3F1 mice. The fractions were assayed for their ability to bioactivate APAP to N-acetyl-p-benzoquinone imine, which was trapped as APAP-glutathione conjugates or APAP-protein adducts, and for dimethyl-nitrosamine-N-demethylase (DMN), 4 nitrophenol hydroxylase (4-NPOH), and phenacetin-O-deethylase (PAD) activities. Activity in the crude mitochondrial-rich (10,000 x g pellet) fraction was low and PG had no effect. PG inhibited DMN and 4-NPOH, indicators of IIE1-dependent activity, and the formation of APAP-glutathione conjugates and APAP-protein adducts in both heavy (15,000 x g pellet) and light (100,000 x g pellet) microsomes. PAD, a measure of IA2-dependent activity, was not inhibited. These data demonstrate that PG selectively inhibits IIE1 activity, including the bioactivation of APAP, and implicates this as the mechanism for PG-mediated protection of APAP hepatotoxicity in mice. PMID- 8355560 TI - The effect of chronic administration of cyclosporin A on phenytoin pharmacokinetic parameters in the rat. AB - The potential for a drug interaction between cyclosporin A and phenytoin was investigated in rats. Rats were treated daily for 14 days with cyclosporin A (50 mg/Kg, s.c.) and on the day of the experiment phenytoin (10 mg/Kg) was administered intravenously. The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group. However, total body clearance was similar in both groups. Plasma levels of urea, aspartate aminotransferase (AST) and glucose were significantly higher in the cyclosporin A treated group than the control group. It was concluded that the observed changes could have been, at least in part, due to an inhibitory effect of cyclosporin A on liver drug metabolizing enzymes and/or liver and kidney damage. PMID- 8355559 TI - Effects of cholecystokinin and gastrin on gastroduodenal motility and coordination in chickens. AB - Cholecystokinin (CCK) has not been isolated from chicken gut yet and there has been no study on the effects of chicken gastrin (CG), the only gastrin/CCK peptide isolated from avian gut, on gastrointestinal motility. The main objective was to study the effects of CCK and CG on gastroduodenal motility and coordination in chickens. Electrodes for electromyography were implanted in the stomach and proximal and distal duodenum of 4 wk old chickens. Sulphated CCK octapeptide (CCK8) (10(-10) to 10(-8) moles/kg), CCK-tetrapeptide (CCK4) (2 x 10( 10) to 2 x 10(-8) moles/kg) and CG (3 x 10(-10) to 10(-8) moles/kg) were given in a 10 min i.v. infusion. All these peptides induced a dose-dependent inhibition of gastric motility. CCK8 induced a duodenal hyperactivity whereas CCK4 and CG induced a duodenal inhibition. Neither the CCK-A receptor antagonist L364,718 nor the CCK-B receptor antagonist L365,260 (10(-9)-10(-7) moles/kg) antagonized CCK8 actions. From these results we suggest that the receptors mediating CCK effects are different from those of mammals. The site of action for these peptides is the same in the stomach whereas in the duodenum there are two different ones, one mediating excitation and the other inhibition. These results suggest a physiological role for CCK regulating gastroduodenal motility in birds. PMID- 8355561 TI - Increased concentrations of atrial and plasma atrial natriuretic peptide in castrated male rats. AB - The effects of orchiectomy and testosterone replacement on the plasma concentration and the atrial stores of atrial natriuretic peptide (ANP) were studied in the rats. Male rats were orchiectomized (Orc) three weeks before replacement with testosterone propionate (TP, 20 mg/ml/kg body weight) or sesame oil for five days. Immunoreactive ANP (IR-ANP) in the extracted right atria and plasma of experimental rats was measured. Plasma ANP concentrations were 206 +/- 22, 927 +/- 151, and 264 +/- 61 pg/ml in normal control, Orc, and Orc + TP rats, respectively. ANP contents in right atria were higher in Orc (108 +/- 9 ng/mg tissue) and TP-treated Orc rats (123 +/- 9 ng/mg tissue) than in normal animals (32 +/- 7 ng/mg tissue). These results indicate an increased plasma concentration and atrial stores in the castrated male rats. Replacement of testosterone in the castrated male rats does not decrease the atrial ANP stores, but decreases the plasma ANP concentration. PMID- 8355562 TI - Cytosolic lipogenic enzymes: effect of fibric acid derivatives in vitro. AB - The effect of fibric acid derivatives, clofibric acid (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on hepatic cytosolic enzymatic activities involved in saturated fatty acid synthesis has been estudied in vitro. From all the activities tested (fatty acid synthetase, acetyl-CoA carboxylase, ATP-citrate lyase, malic enzyme, malic dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase), only acetyl-CoA carboxylase and glucose-6 phosphate dehydrogenase were significantly inhibited by fibrates, with the following order of potency: GFB > BFB > > CFB. The characteristics of the inhibition phenomena (IC50, kinetic analysis, time and protein dependence, etc) and their transcendence to the effects of fibric acid derivatives in vivo are discussed. PMID- 8355563 TI - In vivo uptake of ethanol and release of acetate in rat liver and GI. AB - The concentration gradients of ethanol and acetate across liver and GI were determined in overnight starved rats infused with ethanol at a rate (15 mu mol/min/rat) below and a rate (30 mu mol/min/rat) exceeding the rate of ethanol disposal in the animals. Plasma concentrations of ethanol in the systemic circulation reached steady-state levels of approximately 0.6 mM between 30 and 60 min during low rate of infusion; increased steadily from 3.5 mM at 30 min to 6.4 mM at 2 h during high rate of infusion. GI metabolism was determined by concentration differences in aorta and portal vein; hepatic metabolism by differences in hepatic influx and hepatic veins. Hepatic influx was the sum of the concentrations in aorta and portal vein, each multiplied by their fractional contributions to hepatic blood supply. At low rate of infusion, hepatic extraction of ethanol was nearly complete and could be accounted for entirely by the acetate released from liver. The concentrations of ethanol in aorta were greater but not significantly than that in portal vein. At high rate of infusion, hepatic and GI gradients of ethanol remained constant despite changes in circulating concentrations of ethanol. The concentration gradients of ethanol and acetate across liver, though different in signs, were identical in magnitude. GI gradient indicating uptake of ethanol was statistically significant and was about 30% of hepatic gradient. Enzyme activity of alcohol dehydrogenase in stomach was found to be about 10% of that in liver. Our results thus show that acetate generated during ethanol oxidation is completely released from liver in rats, in either conscious or anesthetized state under submaximal or maximal condition of ethanol disposal, and that GI metabolism of circulating ethanol can be as high as one third of the metabolism in liver. PMID- 8355564 TI - Cardiovascular effects of adenosine and its analogs in anaesthetized rats. AB - In order to define the purinergic receptors subtype involved in the control of cardiovascular activity, the effects of intracerebroventricular (icv 3rd ventricle) or intravenous (i.v.) injection of purinergic agonists and antagonists were evaluated on arterial blood pressure and heart rate of anaesthetized normotensive adult male rats. Adenosine (Ado) an A1 and A2 purinergic receptors agonist, N6-cyclohexyladenosine (CHA), an A1 receptor agonist and 5'-(N cyclopropyl)-carboxamidoadenosine (CPCA), an A2 purinergic receptor agonist, were administered in rats by icv (0.01-0.05-0.1 microgram) and i.v. (0.1-0.5-1 microgram/kg) injections. The animals treated with adenosine were either pretreated with an A1 (8-cyclopenthyl-1,3-dimethylxanthine, CPT) an A2 (3,7dimethyl-1-propargylxanthine, DMPX) or an A1-A2 (aminophylline, APH) purinergic receptor antagonist by icv (0.05 microgram) or i.v. (0.5 microgram/kg) injected or not at all pretreated. Ado, CPCA and CHA produced a dose-dependent decrease in arterial blood pressure and heart rate. The effects of CHA were less marked than those caused by Ado and CPCA. The icv and i.v. pretreatment with aminophylline, CPT and DMPX inhibited arterial hypotension and bradycardia induced by Ado, CHA and CPCA. The inhibitor effects of aminophylline and DMPX were stronger than those caused by CPT. These results showed that in the cerebral areas near the 3rd ventricle the purinergic system plays an important role in the control of cardiovascular function. The involvement of A2 purinergic receptors after administration of adenosine or its analogs on central and peripheral cardiovascular activity was also confirmed. PMID- 8355565 TI - Production of fibroblast-pneumocyte-like factor by fetal rabbit lung fibroblasts: isolation and effects of it and related factors on fetal type II cells in vitro. AB - Fetal lung fibroblasts interact with type II epithelial cells, inducing their maturation. This interaction arises by secretion of factors which alter fetal type II cell function. To analyze these factors, conditioned medium (CM) was produced by exposing serum-free minimum essential medium, with [35S]methionine (5 microCi/ml), to confluent cultures of fetal rabbit lung fibroblasts. This medium was tested for ability to stimulate [3H]choline incorporation by fetal type II cells and subsequently fractionated on molecular weight filtration columns P60 (2.5cm x 90cm; NMW cutoff, 60kd; 1M acetic acid) and A1.5m (2.5cm x 90cm; NMW cutoff, 1,500kd; Tris-buffered saline) and a hydroxyapatite column (HT) (1.5cm x 30cm; NaCl and 0.01-0.3M phosphate). Crude medium stimulated choline incorporation into phosphatidylcholine. [35S]methionine was resolved in void volume material and in material of apparent molecular weight of 6000 daltons on the P60 filtration column. Filtration on the A1.5m column showed two major fractions with radiolabel incorporation. Each of these was resolved into two subfractions on HT chromatography. The high molecular mass fraction contained material which stimulated [3H]choline incorporation by fetal type II cells. The low molecular mass fraction tended to inhibit [3H]choline incorporation. The second subfractions of both the first and second primary fractions inhibited [3H]thymidine incorporation into DNA by fetal type II cells. SDS-PAGE electrophoresis and autoradiography showed that under reducing conditions, each peak contained several proteins. However few of these displayed radioactivity. These results indicate that protein factors produced by fetal lung fibroblasts may be involved in regulating both differentiation and replication of fetal type II cells. PMID- 8355566 TI - Disparate effects of phosphoramidon on blood pressure in SHR and DOCA-salt hypertensive rats. AB - Phosphoramidon inhibits both endothelin converting enzyme (ECE) and neutral metalloendopeptidase (NEP). The contribution of ECE and NEP inhibition to the antihypertensive effects of phosphoramidon was investigated in SHR and DOCA-salt hypertensive rats. SCH 32615, an active acid of the potent and selective NEP inhibitor prodrug SCH 34826 was used as a reference compound. Intravenous infusion of SCH 32615 (1.0 mg/kg/min x 2 hr) or phosphoramidon (0.3 and 1.0 mg/kg/min x 2 hr) did not reduce blood pressure (BP) in conscious SHR. The combination of SCH 32615 (100 mg/kg + 1.0 mg/kg/min) and phosphoramidon (0.3 mg/kg/min) also did not alter BP in SHR. In comparison, the BP of conscious DOCA salt rats was significantly reduced by phosphoramidon (0.01, 0.1 and 1.0 mg/kg/min x 2 hr) (-28 +/- 6, -51 +/- 5 and -85 +/- 6 mmHg, respectively). SCH 32615 (100 mg/kg, i.v.) over 5 min followed by a sustained infusion of 1.0 mg/kg/min for 2 hr also reduced BP by 49 +/- 7 mmHg (P < .05) in DOCA-salt rats. However, phosphoramidon (0.1 mg/kg/min x 2 hr) failed to cause a further reduction in BP in DOCA-salt rats concurrently receiving SCH 32615. In contrast, a higher dose of phosphoramidon (0.3 mg/kg/min) in combination with SCH 32615 caused a greater reduction in BP in DOCA-salt rats than SCH 32615 alone. In anesthetized normotensive rats, phosphoramidon (0.01-1.0 mg/kg/min x 30 min) dose dependently inhibited the BP responses to big endothelin-1 (BET-1) without blocking the pressor responses to ET-1. SCH 32615 failed to attenuate the pressor responses to either BET-1 or ET-1. The results indicate that SCH 32615 lacks in vivo ECE inhibitory activity. It is concluded that the antihypertensive action of SCH 32615 and low doses of phosphoramidon can be attributed to the inhibition of NEP which may presumably cause an accumulation of ANF. In comparison, at higher doses phosphoramidon causes a further reduction of BP in DOCA-salt hypertensive rats by inhibition of endothelin bioconversion. PMID- 8355567 TI - 16 beta-[18F]fluoromoxestrol: a potent, metabolically stable positron emission tomography imaging agent for estrogen receptor positive human breast tumors. AB - 16 beta-[18F]Fluoromoxestrol (beta FMOX, 1) is a highly selective, metabolically stable estrogen with potential as a receptor imaging agent. It demonstrates receptor-mediated uptake in the immature rat in the estrogen receptor-rich primary target tissues, uterus and ovaries, as well as, in receptor-poor secondary target tissues, muscle, thymus and kidneys; uptake in the uterus is nearly four times that of the clinically useful 16 alpha-[18F]fluoroestradiol (FES), most likely due to the extended lifetime of the labeled beta FMOX in the blood afforded by its relatively slow metabolism. In vivo and in vitro studies demonstrate a nearly four-fold decrease in metabolism rate between beta FMOX and FES. Dosimetry studies indicate radiation absorbed doses comparable to FES. beta FMOX possesses desirable imaging characteristics and may prove to be a clinically useful imaging agent. PMID- 8355569 TI - Naltrexone treatment attenuates the inhibitory effect of nicotine treatment on serum LH in rats. AB - The hypothesis that endogenous opioids might have a role in mediating the suppressive effects of nicotine on serum LH concentrations in rats was investigated. Naltrexone treatment prevented the inhibitory effect of high doses of nicotine on serum LH concentrations. Nicotine treatment also prevented the stimulatory effect of naltrexone on serum LH concentrations. These results suggest that the inhibitory effects of nicotine on serum LH concentrations involve an opioidergic component. PMID- 8355568 TI - Radiochemical quantitation of conjugated dienes in rat hepatocytes exposed to oxyradicals. AB - Conjugated dienes are fingerprint signatures of oxidant damage in cells. We used a radiochemical method based on the Diels-Alder reaction of 14C-labeled tetracyanoethylene with conjugated dienes to delineate the changes of its levels in ischemia-reperfusion in the rat liver. To more directly illustrate the kinetics of diene appearance in hepatocytes, we have applied the same radiochemical assay to rat hepatocytes exposed to xanthine oxidase and hypoxanthine. We observed that the conjugated dienes rose to a maximum under our condition at approximately 10 min, while Trolox--an antioxidant derived from vitamin E found previously to protect rat hepatocytes from oxyradical damage (2)- markedly reduced the formation of conjugated dienes. PMID- 8355570 TI - The influence of reproductive hormones on ANF release by rat atria. AB - The effects of subcutaneous (sc) administration of estradiol (50 micrograms/100 microliters/day x 10 day) or testosterone (15 mg/100 microliters twice a week x 2 weeks) on ANF release were examined in isolated perfused rat atria. The concentration of ANF in the perfusate was measured by radioimmunoassay, under basal conditions (atrial wall unstressed), and during atrial distention (intraluminal pressure raised to 4, 6, and 10 cm water). In both male and female control (vehicle-injected) groups, increased atrial pressure resulting in distention of the atrium caused a significant increase in ANF release. Estradiol increased basal secretion of ANF but did not influence stretch-induced stimulation of ANF secretion. By contrast, although testosterone did not affect basal secretion, it completely abolished the stretch-induced increase in ANF secretion. Neither estradiol nor testosterone affected atrial compliance. PMID- 8355571 TI - Increased content of epidermal growth factor in platelet lysates in non-insulin dependent diabetes mellitus. AB - We evaluated the content of EGF in platelet lysates obtained from 49 patients with non-insulin-dependent diabetes mellitus (NIDDM)(18 males, 31 females, age 58 +/- 13 years) and from 23 clinically healthy control subjects (11 males, 12 females, age 53 +/- 18 years). Platelets were collected from platelet-rich plasma and lysed. EGF was determined by radioimmunoassay. The immunoreactive EGF content in the platelet lysates in diabetic patients significantly exceeded that of control subjects (44.9 +/- 18.5 pg/mm3platelet vs. 34.2 +/- 7.8 pg/mm3platelet, mean +/- SD p < 0.008). In performing multiple regression analysis with ten clinical parameters, urinary albumin excretion (F = 16.1, r = 0.551, p < 0.001), duration of diabetes (F = 13.0, r = 0.511, p < 0.001) and the presence of diabetic proliferative retinopathy (F = 8.8, p < 0.01) were significantly associated with irEGF content in platelet lysates. These observations suggest that the amount of EGF in platelets may increase with the progression of diabetic complications. The mechanism for the increase of EGF in platelets remains to be clarified. PMID- 8355572 TI - Recombinant interleukin-1 receptor antagonist protein prevents sensitization and intestinal anaphylaxis in guinea pigs. AB - Recombinant interleukin-1 receptor antagonist protein (rlRAP, 0.5 mg/kg) administered intraperitoneally in guinea pigs one hour before primary and booster parenteral sensitization (1 ml) by cow milk, led to a reduced immunoglobulin E (IgE) production, as displayed by a passive cutaneous anaphylaxis test. rlRAP administered intraperitoneally in sensitized guinea pigs at 0.5 mg/kg 10 min before challenge administration (beta-lactoglobulin, 100 mg per os), also prevents the colonic motor and secretory changes induced by intestinal anaphylaxis. These results suggest the involvement of interleukin-1 in food allergy and evidence a double protective role for rlRAP in food hypersensitivity. PMID- 8355573 TI - Chronic effects of monoamine oxidase-B inhibitors on the behaviour of aged mice. AB - In order to measure the chronic effects of monoamine oxidase-B (MAO-B) inhibitors on the physical and cognitive condition of 60 aged male mice, 1-deprenyl or N methyl-N-(2-pentyl)-propargylamine (M-2-PP) were administered in drinking water (10 micrograms/ml/day) for 37 weeks. The spontaneous open-field locomotion, balancing ability and weight gain of the mice were assessed continuously. At the end of the study the spatial learning ability of all surviving mice was assessed in a Morris water maze. Both drug groups exhibited a reduction in spontaneous locomotion at the same rate as the control group, while there were no changes in balancing ability. The mice receiving 1-deprenyl, however, performed the water maze task less well than the control group. The mice receiving 1-deprenyl also gained weight at a significantly reduced rate compared to both the M-2-PP and water treated groups. A brain MAO assay indicated that MAO-B was completely inhibited by both drugs while MAO-A remained unchanged. The implications of these data on longevity studies using 1-deprenyl and other MAO-B inhibitors are discussed. PMID- 8355575 TI - Effect of clofibric acid on the turnover of the fatty acid-binding protein identified in cultured endothelial cells from bovine aorta. AB - Several types of fatty acid-binding proteins are found in mammalian cells. Cultured endothelial cells from bovine aorta were shown to contain exclusively the cardiac-type fatty acid-binding protein (cFABP) with a mean concentration of 90 ng cFABP/mg extract protein. Only small variations were observed from passage to passage. In pulse-chase labeling experiments with L-[35S]methionine, a half life of 4.0 d was measured for cFABP which is about two times longer than the average half-life of the extracted proteins. These data imply that in aortic endothelial cells cFABP is not subject to short-term regulation. However, addition of clofibric acid to the culture medium led to a shortening of the half life of cFABP, which was compensated for by an increase in its biosynthesis. The turnover of the bulk of extract proteins remained unchanged when the cells were challenged with clofibric acid. PMID- 8355574 TI - Protein kinase C-dependent stimulation of phospholipase D in phospholipase C treated fibroblasts. AB - Treatment of [14C]choline- or [14C]ethanolamine-labeled NIH 3T3 fibroblasts with Bacillus cereus phosphatidyl-choline-specific phospholipase C (PLC) enhanced phospholipase D (PLD)-mediated hydrolysis of the respective 14C-labeled phospholipids. PLD activity was stimulated by 1.5 U/mL of PLC and by 100 nM of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) to similar extents. Treatment of [14C]palmitic acid-labeled fibroblasts with PLC in the presence of ethanol also enhanced PLD-mediated formation of phosphatidylethanol; the effects of PLC and PMA were nonadditive. PLC had no effect on PLD activity in fibroblasts in which PKC was down-regulated by prolonged (24 h) treatment with 300 nM PMA. These data indicate that treatment of fibroblasts with exogenous PLC results in PKC-dependent activation of PLD. PMID- 8355576 TI - Role of lipid structure in the activation of phospholipase A2 by peroxidized phospholipids. AB - The time course of hydrolysis of a mixed phospholipid substrate containing bovine liver 1,2-diacyl-sn-glycero-3-phosphocholine (PC) and 1,2-diacyl-sn-glycero-3 phosphoethanolamine (PE) catalyzed by Crotalus adamanteus phospholipase A2 was measured before and after peroxidation of the lipid substrate. The rate of hydrolysis was increased after peroxidation by an iron/adenosine diphosphate (ADP) system; the presence of iron/ADP in the assay had a minimal inhibitory effect. The rate of lipid hydrolysis was also increased after the substrate was peroxidized by heat and O2. Similarly, peroxidation increased the rate of hydrolysis of soy PC liposomes that did not contain PE. In order to minimize interfacial factors that may result in an increase in rate, the lipids were solubilized in Triton X-100. In mixtures of Triton with soy PC in the absence of PE, peroxidation dramatically increased the rate of lipid hydrolysis. In addition, the rate of hydrolysis of the unoxidizable lipid 1-palmitoyl-2-[1 14C]oleoyl PC incorporated into PC/PE liposomes was unaffected by peroxidation of the host lipid. These data are consistent with the notions that the increase in rate of hydrolysis of peroxidized PC substrates catalyzed by phospholipase A2 is due largely to a preference for peroxidized phospholipid molecules as substrates and that peroxidation of host lipid does not significantly increase the rate of hydrolysis of nonoxidized lipids. PMID- 8355577 TI - Structure-function relationships of alkyl-lysophospholipid analogs in selective antitumor activity. AB - This investigation was initiated in order to delineate the structure-function relationship of the anticancer alkyl-lysophospholipids and assess their degree of selective cytotoxicity toward neoplastic cells. A series of glycerol phosphocholine analogs with varying substitutions in the sn-1 and sn-2 position were tested for their inhibitory activity as measured by thymidine incorporation, clonogenic assays and effects on protein kinase C activity against a series of human leukemic cell lines and healthy bone marrow progenitor cells. The IC50 was determined for each of the compounds in each cell line and healthy bone marrow cells following a 4-h incubation. The data indicated that a 16-18 carbon chain at the sn-1 coupled with a short substitution at sn-2 had the broadest antitumor activity and was the least toxic to normal bone marrow cells. The results provide a number of useful leads toward the design and development of potentially more active phospholipid compounds. PMID- 8355578 TI - Differential utilization of eicosapentaenoic acid and docosahexaenoic acid in human plasma. AB - It has recently been shown that the omega 3 fatty acid status in humans can be predicted by the concentration of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma phospholipids [Bjerve, K.S., Brubakk, A.M., Fougner, K.J., Johnsen, H., Midjthell, K., and Vik, T. (1993) Am. J. Clin. Nutr., in press]. In countries with low intake of omega 3 fatty acids, the level of EPA in plasma phospholipids is often only about one-fifth the concentration of DHA. The purpose of this study was to investigate whether this difference in the concentration of these two fatty acids was due to a selective loss of EPA relative to DHA or to a lower dietary intake of EPA. Seven female volunteers ingested four grams of MaxEPA daily for 2 wk and in the following 4 wk they ate a diet almost completely devoid of the long-chain omega 3 fatty acids. The concentrations of the omega 3 fatty acids in the plasma cholesteryl esters, triglycerides and phospholipids and the high density lipoprotein phospholipids were examined at weekly intervals throughout the study. There was a more rapid rise in the concentration of EPA than in DHA levels in the supplementation period in all lipid fractions, but there was a disproportionate rise in DHA relative to EPA in the plasma lipids compared with the ratio in the supplement. In the depletion phase there was a rapid disappearance of EPA from all fractions, such that pre-trial levels were reached by one week post-supplementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355579 TI - Interrelationship of stearic acid content and triacylglycerol composition of lard, beef tallow and cocoa butter in rats. AB - We investigated modes whereby stearic acid (18:0) exerts a neutral or cholesterol lowering effect using dietary fats which provided graded levels of 18:0 and distinct triacylglycerol (TAG) profiles. Male Sprague-Dawley rats (150-175 g) were fed diets containing 0.2% cholesterol and 16% fat from corn oil, or from 1% corn oil plus 15% lard (13.2% 18:0), beef tallow (19.2% 18:0) or cocoa butter (34.7% 18:0) for 3 wk, and then killed in a fasted or fed state. Chylomicron (CM) fatty acid profiles suggested reduced absorption of 18:0 with greater 18:0 intake. CM TAG profiles indicated a reduction or loss of two TAG species compared to the TAG profiles of the stearate-rich diets: 1-palmitoyl-2-oleoyl-3-stearoyl glycerol (POS) and 1,3-distearoyl-2-oleoyl glycerol (SOS). Hepatic total cholesterol concentrations were 54-77% lower (P < 0.01) in the cocoa butter-fed than the lard-and beef tallow-fed groups. The cocoa butter group showed a significantly lower ratio of high-density lipoprotein esterified/free cholesterol than all other groups. Hepatic stearoyl-CoA and oleoyl-CoA concentrations, the substrate and product for hepatic delta 9 desaturase, were not significantly different for corn oil-fed and cocoa butter-fed groups in spite of a large difference in 18:0 intake. These data suggest that the neutral or cholesterol lowering effect of 18:0 is not due to hepatic conversion of stearic to oleic acid, and that POS and SOS are poorly absorbed from stearate-rich dietary fats. PMID- 8355580 TI - Cholesterol synthesis and esterification in isolated enterocytes: regulation by cholesterol and cholestyramine feeding. AB - The purpose of the present study was to investigate the physiological control of the main regulatory enzymes of cholesterol metabolism in isolated enterocytes obtained from chick duodenum, jejunum and ileum. Cholesterol feeding resulted in an inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase and mevalonate 5 pyrophosphate decarboxylase, while cholestyramine feeding increased reductase activity in all the regions studied and decarboxylase activity only in duodenum. Cholesterol feeding markedly increased acyl-CoA:cholesterol acyltransferase, but the effects of cholestyramine were less clear. The effects on transferase activity cannot be due to differences in the availability of acyl-CoA as exogenous substrate as no significant differences were found in acyl-CoA hydrolase activity after any of the dietary treatments. The effects of cholesterol feeding were related to changes in the cholesterol content of epithelial cells, whereas in the case of cholestyramine this relationship was less apparent. PMID- 8355581 TI - Radioprotection of mice by dietary squalene. AB - Male C3H mice were fed a diet containing 2% squalene for 14 d prior to and 30 d subsequent to exposure to 6, 7 or 8 Gy of whole body gamma-irradiation (Cesium 137). After 14 d on squalene-supplemented diet, plasma and jejunal tissue squalene levels were 2X and 15X that of controls. Seven days after irradiation, total white cell counts and total lymphocyte counts were substantially depressed in a radiation dose-dependent manner. Although counts in the squalene group were consistently (18-119%) higher than those in the corresponding dietary control group, the differences between dietary groups at any single dose were not significant. Nuclear area of villus cells in the jejunum of both dietary groups was significantly reduced (20%) by day 11 post-irradiation but the nuclear area in squalene-fed mice was significantly greater (15%) than in controls, before and after irradiation. There were no differences in body weight as a function of either diet or radiation dose prior to the first observations of animal lethality. Animal survival was decreased from 100 to 0% at 30 d post-irradiation by radiation doses of 6-8 Gy, with the greatest difference between dietary groups being observed at 7 Gy (median survival times of 12 and 16 d for control and squalene groups, respectively). Overall, survival of squalene-fed mice was significantly prolonged compared with control-fed mice (P = 0.0054 by censored multiple regression analysis). It is concluded that squalene conferred some cellular and systemic radioprotection to mice receiving these lethal whole-body radiation doses. PMID- 8355582 TI - 2-Alkenyl-4,4-dimethyloxazolines as derivatives for the structural elucidation of isomeric unsaturated fatty acids. AB - Several types of unsaturated fatty acid methyl esters were converted into 4,4 dimethyloxazoline (DMOX) derivatives and analyzed by mass spectrometry to further evaluate the feasibility of using this derivative for locating the positions of double bonds in isomeric fatty acids. Five isomeric 20-carbon tetraenoic acids were analyzed in which the four cis double bonds were systematically moved from the 4,7,10,13- to the 8,11,14,17-positions. It was possible to locate the positions of all four double bonds in the 7,10,13,16- and 8,11,14,17-isomers by appropriate ions differing by 12 atomic mass units. In a similar way the three terminal double bonds in the 4,7,10,13-, 5,8,11,14- and 6,9,12,15-isomers could be assigned. Odd-numbered ions at m/z 139, 153 and 167 which are accompanied by an even mass ion at 138, 152 and 166, respectively, are diagnostic for DMOX derivatives of acids with their first double bond, respectively, at positions 4, 5 and 6. It was thus possible to assign the location of all four double bonds in these three isomers. A comparison of the spectra of the DMOX derivatives of 17,17,18,18-d4 vs. 9,10,12,13-d4 linoleic acid suggests that double bonds preferentially migrate toward the polar end of the molecule prior to fragmentation. The merit of using DMOX derivatives to locate double-bond positions in mono- and dicarboxylic acids, produced during beta-oxidation of polyunsaturated fatty acids, was evaluated. The spectra of 3-cis- and 4-cis decenoic acids differ as do the spectra of 8-carbon dicarboxylic acids with their double bonds at positions 3 and 4. PMID- 8355583 TI - Acidic hydrolysis of plasmalogens followed by high-performance liquid chromatography. AB - A simple, quantitative method for determining the plasmalogen content of small samples is reported here. The method uses the different susceptibility to acid catalyzed hydrolysis of the alkyl, alkenyl and acyl linkages to separate the plasmalogen subclass from the other two non-labile subclasses. Hydrolysis of plasmenylethanolamine and plasmenylcholine was complete after 4 and 1 min of acid treatment, respectively. The acid-catalyzed hydrolysis did not alter the phospholipid fatty acid composition, making this method useful for fatty acid compositional analysis of the plasmalogen subclass. High-performance liquid chromatography was used for separations, and phospholipids were quantitated by assay of lipid phosphorus or by direct quantitation of peak area. Using this method, small amounts (10 nmol) of ethanolamine glycerophospholipid and choline glycerophospholipid are subjected to acid-catalyzed hydrolysis and subsequent separation of the resulting lysocompounds obtained from plasmalogens from the more acid-stable alkylacyl and diacyl glycerophospholipid fractions. Our values for plasmalogens from commercial preparations of choline and ethanolamine glycerophospholipids agree with literature values. The usefulness of the method is demonstrated for small glycerophospholipid samples that are equivalent to samples from cultured neural cells. PMID- 8355584 TI - Time response of cholesterol synthesis inhibition by compactin-related compounds. In vitro quantitation of the "escape phenomenon". AB - The time course of the inhibition of cholesterol synthesis by low and high doses of mevinolin and monacolin X were studied in normal human skin fibroblasts, fibroblasts without low density lipoprotein receptor and HepG2 hepatoma cells. Low doses of the inhibitors (0.2 ng/mL) caused a sharp decrease in the rate of cholesterol synthesis during the first 2-3 h, which gradually increased to about 40% during the next 6 h. Further incubation led to a decrease or stabilization of the cholesterol synthesis rate. High doses of the drugs (100 mg/mL) strongly inhibited cholesterol synthesis during the first 2-3 h, followed by a moderate increase during the next 20 h. No drug or tissue selectivity was observed. PMID- 8355585 TI - Oxidative modification of triglyceride-rich lipoproteins in hypertriglyceridemic rats following magnesium deficiency. AB - Hypertriglyceridemia observed in magnesium (Mg)-deficient rats was associated with a significant increase in the very low-density lipoprotein (VLDL) plus low density lipoprotein (LDL) fractions. The results from in vitro copper-induced lipid peroxidation, expressed in terms of conjugated dienes and thiobarbituric acid reactive substances content, showed that VLDL + LDL particles from Mg deficient rats were more susceptible to oxidative damage than lipoproteins from control rats. These results suggest that the mechanism responsible for the atherogenicity and tissue damage characteristic of Mg deficiency may be mediated by an increased susceptibility of triglyceride-rich lipoproteins to peroxidation in hypertriglyceridemic animals. PMID- 8355586 TI - Lipid biosynthesis in cultured arterial smooth muscle cells is related to their phenotype. AB - During the atherogenic process in vivo, arterial smooth muscle cells (SMC) undergo changes in their phenotype. In the present study, rat SMC from primary cultures and from subcultures before 10 and after 200 passages, showing contractile-like, synthetic and transformed phenotypes, respectively, were compared in regard to their lipid content and biosynthesis. The rationale for comparing these phenotypes rests in the similar changes in phenotype of SMC that occur in the formation and progression of atherosclerotic lesions. Phenotype changes were shown to be associated with changes in the phospholipid content of SMC. Phospholipid levels increased, but not as significantly as did cholesterol levels when passing from contractile to synthetic and transformed cells (1.23 +/- 0.18, 2.28 +/- 0.26 and 3.25 +/- 0.23 micrograms/10(6) cells, respectively). Cholesterol normalized in respect to cell protein was increased to the same extent. Lipid synthesis as judged by [14C]acetate incorporation was increased 3- to 12-fold in the synthetic and transformed cells, respectively, compared to contractile cells. After thin-layer chromatography, radioactivity was shown to be markedly increased in most of the lipid fractions, but label in the cholesterol fraction of synthetic and transformed cells was increased by 7- and 21-fold, respectively. Thus, SMC in vitro were shown to drastically increase cholesterol biosynthesis associated with phenotype changes. Such changes are known to occur in vivo and might represent a critical step in the deposition of excess cholesterol within foam cells. PMID- 8355587 TI - The esterified plasma fatty acid profile is altered in early HIV-1 infection. AB - Previous studies have shown that alterations in micronutrient utilization occur in patients with Acquired Immune Deficiency Syndrome. In this study, total plasma fatty acid composition was measured in 36 homosexual men infected with the Human Immunodeficiency Virus 1 (HIV-1) and in 17 HIV-1 seronegative homosexual men in order to evaluate differences associated with early HIV-1 infection. Immunologic assessment included CD4 cell number count and lymphocyte blastogenesis in response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). The mean total amount of omega 6 polyunsaturated fatty acids (18:2 and 20:4) was significantly lower in the HIV-1 seropositive subjects (38 +/- 8.1% SD) as compared to HIV-1 seronegative subjects (43 +/- 4.2%; P = 0.0027). This was also reflected in a higher level of total saturated fatty acids (16:0 and 18:0) in HIV 1 seropositive subjects (30 +/- 2.2% vs. 26 +/- 2.8%; P = 0.0001). The ratio of linoleic to arachidonic acid (18:2 to 20:4) was higher in the HIV-1 seropositive group (6.76 +/- 4.88) compared to the HIV-1 seronegative group (4.86 +/- 1.37; P = 0.0213). The response to PHA in seropositive subjects correlated inversely with total plasma omega 6 fatty acids (r = -0.36; P = 0.027), and directly with the 18:2 to 20:4 ratio (r = 0.33; P = 0.046). CD4 cell counts and the response to PWM did not correlate with plasma fatty acid levels in HIV-1 seropositive subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355588 TI - Atherosclerosis and plasma and liver lipids in nine inbred strains of mice. AB - Nine inbred strains of mice, which are progenitors of recombinant inbred sets, were evaluated for aortic lesion formation and plasma and liver lipid levels. This survey was done to determine if a semi-synthetic high-fat diet could elicit the same extent of diet-induced atherosclerosis as that observed in mice fed a natural ingredient high-fat diet and to discover strain-specific plasma and liver lipid variants for future genetic characterization. Evaluation of aortic lesions after 18 wk of diet consumption showed that strains C57BL/6J, C57L/J, SWR/J and SM/J were susceptible to atherosclerosis and that A/J, AKR/J, C3H/HeJ, DBA/2J and SJL/J were relatively resistant. High-density lipoprotein cholesterol (HDL-C) levels were negatively correlated to lesion formation. Susceptible strains had decreased HDL-C levels when switched from chow to the semi-synthetic high-fat, high cholesterol diet, whereas resistant strains either showed no change or a slight increase in HDL-C levels. The exception to this pattern was found in SM mice, which were susceptible to aortic lesion formation but maintained the same HDL-C level on both chow and high-fat diets. HDL size differed among the strains, and levels of plasma apolipoprotein A-I and A-II correlated with HDL-C levels. Liver damage was not correlated to HDL-C levels or to susceptibility to atherosclerosis. Mice from strain A, which are resistant to atherosclerosis, had evidence of liver damage as observed by elevated levels of plasma alanine aminotransferase activity, by liver histology, by increased liver weight and by exceptionally high hepatic cholesterol content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355589 TI - Adipose glycerolipid formation: effect of nutritional and hormonal states. AB - The potential of glycerolipid formation from sn-glycerol-3-phosphate (GP) and 2 monoacylglycerol (MG) was studied in adipose microsomal fractions under various nutritional and hormonal states. Glycerolipid formation from GP was followed in the presence of [14C]glycerol-3-phosphate and palmitoyl-CoA and was assayed by measuring the formation of butanol-soluble product, consisting mainly of [14C]phosphatidate. Glycerolipid formation from MG was determined in the presence of 2-mono-oleyl glycerol and [14C]palmitoyl-CoA, and was estimated by the formation of both [14C]di- and triacylglycerol. Glycerolipid formation from GP was decreased significantly during food deprivation, in experimental diabetes, in the presence of lipolytic hormone, and during aging. Glycerolipid formation from MG did not change under these conditions and continued at the same rate as observed in control animals. The rate of glycerolipid formation from GP was 7-20 times greater than from MG in the various fat depots. Measurement of the adipose monoacylglycerol concentration did not show any correlation with the glycerolipid formation from MG. The studies suggest that glycerolipid formation from MG is active in various fat depots, and is substantial when glycerolipid formation via GP is impaired. PMID- 8355590 TI - The esterification of cholesterol in the yolk sac membrane of the chick embryo. AB - The uptake of lipid from the yolk by the yolk sac membrane of the chick embryo is accompanied by the rapid esterification of a large proportion of the yolk cholesterol. This could arise from enhanced acyl-CoA:cholesterol acyltransferase (ACAT) activity and/or inhibition of cholesteryl ester hydrolase (CEH) activity. The activity of ACAT was therefore measured in microsomes obtained from yolk sac membranes at various stages of development. A high level of activity (up to 929 pmol of cholesteryl oleate formed per min per mg protein) was found during the second half of this period. Supplementation with exogenous cholesterol stimulated ACAT activity in microsomes obtained from the tissue at the earlier, but not at the later, stages of development suggesting that the enzyme became saturated with microsomal cholesterol as development proceeded. Correlating with this, the concentration of cholesterol in the microsomes increased 4-fold between 9 and 20 d of development. The activity of CEH was very low in the microsomes and could not be detected in the cytosolic fraction. The activity of a protein, which has been shown to function as an inhibitor of CEH, was found to be present at all stages of development. The high activity of ACAT, together with the low activity of CEH and an active CEH inhibitor protein is a combination well suited to promote an essentially unidirectional conversion of cholesterol to cholesteryl ester. This process may be a major determinant of the rate of lipid transfer from the yolk to the embryo. PMID- 8355591 TI - Nervonic acid in red blood cell sphingomyelin in premature infants: an index of myelin maturation? AB - The present study addresses the question whether nervonic acid (24:1n-9) accumulation in sphingomyelin (SM) of red blood cells (RBC) could yield information on cerebrum maturation in premature infants. The study included 28 premature eutrophic infants of 31.5 wk gestational age. Eleven were fed with human milk, nine with a regular formula and eight with an alpha-linolenate enriched formula. The fatty acid composition of the SM fraction was determined by gas-liquid chromatography on a 50-m fused silica capillary column. At 32 wk gestational age, the main fatty acids in SM were 16:0, 18:0, 20:0, 22:0, 24:0 and 24:1n-9. After five weeks of feeding, at week 37 of postconceptional age, the most striking variation was a rise in 24:1n-9, from 9.9 +/- 0.7 to 12.8 +/- 0.9 (P < 0.02), regardless of regimen in all three feeding groups. The rise in 24:1n 9 after birth in premature eutrophic infants is the beginning of a trend toward the higher levels in 24:1n-9 observed in mature newborns and older infants. The 24:1n-9 level in SM of RBC from premature infants may reflect 24:1n-9 levels in SM of brain and could thus reflect brain maturity. PMID- 8355592 TI - Phospholipid molecular species from human placenta lipids. AB - The phospholipid molecular species from a large-scale preparation of human placenta lipids were analyzed. The major placental phospholipids were choline glycerophospholipids (CPL) (53.2 wt%), sphingomyelin (21.7 wt%) and ethanolamine glycerophospholipids (EPL) (14.6 wt%). 1,2-Diacyl-glycerophosphocholine was the most abundant subclass of CPL (91.7 mol%), while EPL contained 1,2-diacyl (54.6 mol%) and 1-alk-1'-enyl-2-acyl (43.8 mol%) subclasses. The level of polyunsaturated fatty acids (PUFA) in total phospholipids was remarkably constant (38.4-39.9 mol%) within all placental batches tested. The long-chain PUFA, mainly 20:4n-6 and 22:6n-3 of the n-6 and n-3 series, respectively, were found in high proportion in all phospholipid classes, especially in EPL (46.7 mol%) and in inositol glycerophospholipids (IPL) (39.9 mol%). CPL and serine glycerophospholipids were much richer in 18:1n-9 and 18:2n-6. High levels of molecular species with arachidonic acid in the sn-2 position were found particularly in 1-alk-1'-enyl-2-acyl-glycerophosphoethanolamine (with 24.0 mol% 16:0 and 22.0 mol% 18:0 in sn-1 position) and in 1,2-diacyl glycerophosphoinositol with 42.6 mol% 18:0 in sn-1 position. EPL subclasses were rich in 22:6n-3, which occurs mainly as 16:0/22:6n-3 (11.7 mol%) in the plasmalogen form and as 18:0/22:6n-3, 16:0/22:6n-3 and 18:1/22:6n-3 in the diacyl forms. Based on their availability and composition, placental phospholipids could be of interest, for example, for supplementing artificial milk preparations with n-3 and n-6 long-chain PUFA for newborn infants with insufficiently developed 18:2n-6 and 18:3n-3 desaturation/elongation. PMID- 8355593 TI - Triacylglycerol structure of human colostrum and mature milk. AB - Because triacylglycerol (TAG) structure influences the metabolic fate of its component fatty acids, we have examined human colostrum and mature milk TAG with particular attention to the location of the very long chain polyunsaturated fatty acid on the glycerol backbone. The analysis was based on the formation of various diacylglycerol species from human milk TAG upon chemical (Grignard degradation) or enzymatic degradation. The structure of the TAG was subsequently deduced from data obtained by gas chromatographic analysis of the fatty acid methyl esters in the diacylglycerol subfractions. The highly specific TAG structure observed was identical in mature milk and colostrum. The three major fatty acids (oleic, palmitic and linoleic acids) each showed a specific preference for a particular position within milk TAG: oleic acid for the sn-1 position, palmitic acid for the sn-2 position and linoleic acid for the sn-3 position. Linoleic and alpha linolenic acids exhibited the same pattern of distribution and they were both found primarily in the sn-3 (50%) and sn-1 (30%) positions. Their longer chain analogs, arachidonic and docosahexaenoic acids, were located in the sn-2 and sn-3 positions. These results show that polyunsaturated fatty acids are distributed within the TAG molecule of human milk in a highly specific fashion, and that in the first month of lactation the maturation of the mammary gland does not affect the milk TAG structure. PMID- 8355594 TI - Dietary saturated, monounsaturated, n-6 and n-3 fatty acids, and cholesterol influence platelet fatty acids in the exclusively formula-fed piglet. AB - Platelet lipid composition is important to normal platelet morphology and function, and is influenced by dietary fatty acids and cholesterol. The fatty acid composition and cholesterol content of infant formulas differs from those of human milk, but the possible effects on platelet lipids in young infants is not known. This was studied in piglets fed from birth to 18 d of age with one of eight formulas differing in saturated fatty acid chain length, or content of 18:1, 20:5n-3 plus 22:6n-3, or cholesterol. A reference group of piglets fed sow milk was also studied. Sow milk has a fatty acid composition and cholesterol content similar to that of human milk. Piglets fed formulas high in 18:1 (34.9 40.8% wt fatty acids) and low in 16.0 (< or = 6.5% wt fatty acids) had lower platelet counts and greater platelet size than piglets fed sow milk (40.4% 18:1, 30.7% 16:0). Piglets fed formulas high in 16:0 (27-29.6%) and 18:1 (40-40.6%), or low in both 16:0 (5.9-6.1%) and 18:1 (10.8-11.2%), had similar platelet counts and size to piglets fed sow milk. Platelet phospholipid % 20:4n-6 was lower in all the groups of piglets fed formula than in the group fed sow milk. Addition of fish oil with 20:5n-3 plus 22:6n-3 to the formula further decreased platelet phospholipid 20:4n-6. Addition of cholesterol to the formula increased the platelet phospholipid % 20:4n-6 and platelet volume. PMID- 8355595 TI - Dietary fat effects on hepatic lipid peroxidation and enzymes of H2O2 metabolism and NADPH generation. AB - The purpose of this study was to determine the effects of dietary fat quantity and fatty acid composition on hepatic H2O2-metabolizing systems, activities of NADPH-generating enzymes and lipid peroxidation. One-month-old male C57BL/6J mice were fed one of six diets: (i) 5% fat, rich in 18:2n-6 fatty acid (5% N-6); (ii) 20% fat, rich in 18:3n-3 (N-3); (iii) 20% fat, rich in 18:2n-6 (N-6); (iv) 20% fat, rich in 18:1n-9 (N-9); (v) 20% fat, rich in saturated fatty acids (SAT); and (vi) 20% fat, deficient in essential fatty acids (EFAD); for 11 wk. Comparisons between animal groups receiving different fat quantities showed that activities of glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) and malic enzyme (ME, EC 1.1.1.40) and the levels of conjugated dienes were significantly lower in the N-6 than in 5% N-6 group. Conversely, activities of catalase (CAT, EC 1.11.1.6) and selenium-glutathione peroxidase (SeGSHPx, EC 1.11.1.9) were higher in the N-6 than in 5% N-6 group. Among the five dietary groups receiving 20% fat but differing in fatty acid composition, CAT activity was lower in the N-9 group, SeGSHPx activity was lower in the EFAD group, and glutathione reductase (GSSGR, EC 1.6.4.2) activity was higher in the N-6 than in the N-3, N-9, SAT and EFAD group. The EFAD group had much higher levels of total lipids and conjugated dienes, as well as activities of NADPH-generating enzymes, including G6PDH, ME and isocitrate dehydrogenase (EC 1.1.1.42), than the other four high-fat groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355596 TI - Diabetes increases excretion of urinary malonaldehyde conjugates in rats. AB - The effect of streptozotocin-induced diabetes on the urinary excretion of thiobarbituric acid test-positive materials was examined. In diabetic rats, urinary excretion of thiobarbituric acid reactive substances was increased 5-fold over that in nondiabetic animals. High-performance liquid chromatography of urine samples revealed that five of the six fractions previously found to be increased in vitamin E deficiency [Lee, H.-S., Shoeman, D.W., and Csallany, A.S. (1992) Lipids 27, 124-128] were also significantly increased in streptozotocin-induced diabetes. The data suggest that a high level of oxidative stress is induced by uncontrolled diabetes in rats. PMID- 8355597 TI - A major difference between the divergence patterns within the lines-1 families in mice and voles. AB - L1 retroposons are represented in mice by subfamilies of interspersed sequences of varied abundance. Previous analyses have indicated that subfamilies are generated by duplicative transposition of a small number of members of the L1 family, the progeny of which then become a major component of the murine L1 population, and are not due to any active processes generating homology within preexisting groups of elements in a particular species. In mice, more than a third of the L1 elements belong to a clade that became active approximately 5 Mya and whose elements are > or = 95% identical. We have collected sequence information from 13 L1 elements isolated from two species of voles (Rodentia: Microtinae: Microtus and Arvicola) and have found that divergence within the vole L1 population is quite different from that in mice, in that there is no abundant subfamily of homologous elements. Individual L1 elements from voles are very divergent from one another and belong to a clade that began a period of elevated duplicative transposition approximately 13 Mya. Sequence analyses of portions of these divergent L1 elements (approximately 250 bp each) gave no evidence for concerted evolution having acted on the vole L1 elements since the split of the two vole lineages approximately 3.5 Mya; that is, the observed interspecific divergence (6.7%-24.7%) is not larger than the intraspecific divergence (7.9% 27.2%), and phylogenetic analyses showed no clustering into Arvicola and Microtus clades. PMID- 8355598 TI - Conserved sequence and functional domains in satellite 2 from three families of salamanders. AB - Thirteen satellite 2 elements from Ambystoma talpoideum and 16 from Amphiuma tridactylum were cloned, sequenced, and compared with the satellite 2 consensus from Notophthalmus viridescens. These elements have maintained a high degree of similarity during the 65-200 Myr that the salamander families, represented by the three species, have been separated. The DNA sequences of the consensus elements from A. talpoideum and A. tridactylum are 81% similar, and both are approximately 65% similar to the N. viridescens consensus. In addition to its DNA sequence, the functional properties of satellite 2 have also been conserved. By selecting and analyzing clones that closely mimicked the consensus of each species, we were able to demonstrate that satellite 2 from each species was capable of promoting transcription after injection into Xenopus laevis oocytes and that synthetic transcripts of satellite 2 from each species were capable of catalyzing their own site-specific cleavage. These properties may be related to the process of retroposition, which was previously proposed to be responsible for the genomic proliferation of satellite 2. Each of these functional properties also has general biological interest. PMID- 8355599 TI - Mitochondrial phylogeny of the endemic mouthbrooding lineages of cichlid fishes from Lake Tanganyika in eastern Africa. AB - Of the three cichlid species flocks in eastern Africa, Lake Tanganyika harbors the oldest species assemblage, which is also the most diverse morphologically and behaviorally. For 12 species (20 individuals) of 12 genera of the tribe Ectodini, 852 bp from two segments (cytochrome b and control region) of the mitochondrial genome were sequenced. In addition, orthologous sequences were obtained from eight species (11 individuals) representing other mouthbrooding lineages from Lake Tanganyika. Comparisons of sequence divergences revealed that the single Tanganyikan tribe Ectodini appears to be approximately five times older than the whole Lake Malawi cichlid species flock, suggesting that the radiation of the Tanganyikan mouthbrooding lineages took place long before the species flocks of Lakes Malawi and Victoria evolved. Seven of nine surveyed tribes of Tanganyikan cichlids appear to be approximately equally divergent, and this seems to corroborate the hypothesis of a rapid simultaneous formation of lineages at an early stage in the history of the Lake Tanganyika species flock. The close genetic relationship between the endemic Tropheus lineage and a nonendemic "Haplochromine," Astatotilapia burtoni, indicates that members of the tribe Tropheini may be the sister group of the cichlid flocks of Lakes Malawi and Victoria. The phylogenetic analyses demonstrate the monophyly of the Ectodini and identify the Cyprichromini as their sister group among the Tanganyikan cichlids. Within the tribe Ectodini the molecular data suggest both a branching pattern different than that previously proposed and a subdivision of the Ectodini into four clades, instead of the two originally described. The previously postulated model of morphological transformations believed to be responsible for the drastically different types of ecological specialization found among the Ectodini might therefore be in need of reinterpretation. Characters immediately related to foraging and nutrition seem to be particularly prone to homoplasy, even among members of a single lineage of cichlid fishes. PMID- 8355600 TI - Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species. AB - The Mlc1 gene of Drosophila melanogaster encodes two MLC1 isoforms via developmentally regulated alternative pre-mRNA splicing. In larval muscle and tubular and abdominal muscles of adults, all of the six exons are included in the spliced mRNA, whereas, in the fibrillar indirect flight muscle of adult, exon 5 is excluded from the mRNA. We show that this tissue-specific pattern of alternative splicing of the Mlc1 pre-mRNA is conserved in D. simulans, D. pseudoobscura, and D. virilis. Isolation and sequencing of the Mlc1 genes from these three other Drosophila species have revealed that the overall organization of the genes is identical and that the genes have maintained a very high level of sequence identity within the coding region. Pairwise amino acid identities are 94%-99%, and there are no charge changes among the proteins. Total nucleotide divergence within the coding region of the four genes supports the accepted genealogy of these species, but the data indicate a significantly higher rate of amino acid replacement in the branch leading to D. pseudoobscura. A comparison of nucleotide substitutions in the coding portions of exon 5 and exon 6, which encode the alternative carboxyl termini of the two MLC1 isoforms, suggests that exon 5 is subject to greater evolutionary constraints than is exon 6. In addition to the coding sequences, there is significant sequence conservation within the 5' and 3' noncoding DNA and two of the introns, including one that flanks exon 5. These regions are candidates for cis-regulatory elements. Our results suggest that evolutionary constraints are acting on both the coding and noncoding sequences of the Mlc1 gene to maintain proper expression and function of the two MLC1 polypeptides. PMID- 8355601 TI - Population genetics and phylogenetics of DNA sequence variation at multiple loci within the Drosophila melanogaster species complex. AB - Two regions of the genome, a 1-kbp portion of the zeste locus and a 1.1-kbp portion of the yolk protein 2 locus, were sequenced in six individuals from each of four species: Drosophila melanogaster, D. simulans, D. mauritiana, and D. sechellia. The species and strains were the same as those of a previous study of a 1.9-kbp region of the period locus. No evidence was found for recent balancing or directional selection or for the accumulation of selected differences between species. Yolk protein 2 has a high level of amino acid replacement variation and a low level of synonymous variation, while zeste has the opposite pattern. This contrast is consistent with information on gene function and patterns of codon bias. Polymorphism levels are consistent with a ranking of effective population sizes, from low to high, in the following order: D. sechellia, D. melanogaster, D.mauritiana, and D. simulans. The apparent species relationships are very similar to those suggested by the period locus study. In particular, D. simulans appears to be a large population that is still segregating variation that arose before the separation of D. mauritiana and D. sechellia. It is estimated that the separation of ancestral D. melanogaster from the other species occurred 2.5-3.4 Mya. The separations of D. sechellia and D. mauritiana from ancestral D. simulans appear to have occurred 0.58-0.86 Mya, with D. mauritiana having diverged from ancestral D. simulans 0.1 Myr more recently than D. sechellia. PMID- 8355602 TI - On the detection of nonrandom associations between DNA polymorphisms in natural populations of Drosophila. AB - The capacity to detect nonrandom associations between restriction-map variants was examined in eight gene regions of Drosophila melanogaster (yellow achaetescute, white, Zw, Adh, Est6, and rosy) and D. pseudoobscura (Adh and Xdh), on the basis of published population data. The statistical power from individual pairwise tests was both heterogeneous and generally low across gene regions. Sample sizes larger than those currently being used are needed to ensure any power to detect disequilibrium by individual tests. It is found that the heterogeneity in power is mostly explained by large differences in the intensity of sample disequilibrium among regions. The yellow-achaete-scute, Zw, and Adh loci of D. melanogaster displayed both the highest mean power (approximately 0.4) and a very great disequilibrium (mean absolute values of D' were 0.8-1). By contrast, all the other gene regions exhibited lower mean power (approximately 0.2) and moderate levels of disequilibrium (0.4-0.6). Although the proportion of significant pairwise associations, especially for white, Est6, and rosy in D. melanogaster and for Adh and Xdh in D. pseudoobscura, is more or less close to the type I error, simultaneous-inference significance tests show that gametic disequilibrium is occurring at the eight DNA regions examined. PMID- 8355603 TI - Analysis of a genetic hitchhiking model, and its application to DNA polymorphism data from Drosophila melanogaster. AB - Begun and Aquadro have demonstrated that levels of nucleotide variation correlate with recombination rate among 20 gene regions from across the genome of Drosophila melanogaster. It has been suggested that this correlation results from genetic hitchhiking associated with the fixation of strongly selected mutants. The hitchhiking process can be described as a series of two-step events. The first step consists of a strongly selected substitution wiping out linked variation in a population; this is followed by a recovery period in which polymorphism can build up via neutral mutations and random genetic drift. Genetic hitchhiking has previously been modeled as a steady-state process driven by recurring selected substitutions. We show here that the characteristic parameter of this steady-state model is alpha v, the product of selection intensity (alpha = 2Ns) and the frequency of beneficial mutations v (where N is population size and s is the selective advantage of the favored allele). We also demonstrate that the steady-state model describes the hitchhiking process adequately, unless the recombination rate is very low. To estimate alpha v, we use the data of DNA sequence variation from 17 D. melanogaster loci from regions of intermediate to high recombination rates. We find that alpha v is likely to be > 1.3 x 10(-8). Additional data are needed to estimate this parameter more precisely. The estimation of alpha v is important, as this parameter determines the shape of the frequency distribution of strongly selected substitutions. PMID- 8355604 TI - Protein evolution in different cellular environments: cytochrome b in sharks and mammals. AB - DNA sequences for the mitochondrial cytochrome b gene were determined for 13 species of sharks. Rates and patterns of amino acid replacement are compared for sharks and mammals. Absolute rates of cytochrome b evolution are six times slower in sharks than in mammals. Bivariate plots of the number of nonsynonymous and silent transversions are indistinguishable in the two groups, however, suggesting that the differences in amino acid replacement rates are due primarily to differences in DNA substitution rates. Patterns of amino acid replacement are also similar in the two groups. Conserved and variable regions occur in the same parts of the cytochrome b gene, and there is little evidence that the types of amino acid changes are significantly different between the groups. Similarity in the relative rates and patterns of protein change between the two groups prevails despite dramatic differences in the cellular environments of sharks and mammals. Poor penetrance of physiological differences through to rates of protein evolution provides support for the neutral theory and suggests that, for cytochrome b, patterns of evolution have been relatively constant throughout much of vertebrate history. PMID- 8355605 TI - Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development. AB - Examination of 18 complete and 6 partial sequences of the major outer-membrane protein from 24 chlamydiae isolates was used to reconstruct their evolutionary relationships. From this analysis, assuming that the clades with 100% bootstrap support are correct, come the following conclusions: (1) The tree of these sequences is not congruent with the phylogeny of the hosts, and thus host switching would seem to have occurred, thereby limiting the extent to which there has been coevolution of parasite and host. (2) The tree is also noncongruent with clustering by type of cell infected, thereby limiting the extent to which there has been coevolution of parasite and the cell type that it infects. (3) The tree is also noncongruent with clustering by the organ infected (eyes or genitalia), thereby limiting the extent to which there has been coevolution of parasite and the organ that it infects. (4) The tree is also noncongruent with genital strains arising from lymphogranuloma venereum strains. (5) The tree is also noncongruent with the geographic site at which the isolates were obtained, thereby limiting the extent of divergence explained by geographic separation. (6) There are estimated to be 185 amino acid positions that are invariable (as opposed to unvaried) in the major outer-membrane protein. There are 10 unvaried positions in the variable domains, of which 9 appear to be invariable, giving some reason to hope that development of a vaccine might be possible. (7) The rate of change of this protein is too small to see increased divergence over the time span of isolation of these genes, giving hope to any vaccine having longevity. Bootstrapping supports those portions of the tree on which the first five conclusions above depend. The picture that these results provide is more one of pathogen versatility than one of coevolutionary constraints. In addition, we examined 10 60-KDa, outer-membrane protein-2 genes, all but one of which were from these same strains. The tree was not, among the trachomatis strains, congruent with the major-outer-membrane protein tree, suggesting that gene exchange could be occurring among strains. Moreover, there is an apparent slowdown in divergence in this gene, among the trachomatis strains. PMID- 8355606 TI - Rolling circle-replicating plasmids from gram-positive and gram-negative bacteria: a wall falls. AB - Rolling circle-replicating plasmids constitute a group of small, promiscuous multicopy replicons spread among eubacteria. Until recently, rolling circle replication seemed to be limited to small plasmids from Gram-positive hosts and to single-stranded bacteriophages from Gram-negative bacteria. However, characterization of two small plasmids from Gram-negative hosts has shown that this replication mechanism is general among eubacteria. This review focuses on a family of highly related promiscuous plasmids that replicate by the rolling circle mechanism, and that have been isolated from various Gram-positive bacteria and from the Gram-negative bacterium Helicobacter. They all share homologies at the leading-strand origins and at the initiator of replication proteins. The plasmids of this family have directly repeated sequences at their plus origin of replication, which is located 5' from the start point of the mRNA for the initiation of replication protein. Replication is controlled by an antisense RNA and by a transcriptional repressor protein. The features and regulatory circuits of replication of this plasmid family seem to be unique among rolling circle replicating plasmids. Members of this family replicate autonomously in Gram positive and -negative hosts. PMID- 8355607 TI - Electrophoretic karyotyping of the lignin-degrading basidiomycete Phanerochaete chrysosporium. AB - Electrophoretic karyotyping of the two most widely studied strains of Phanerochaete chrysosporium, BKMF-1767 and ME-446, has been determined using transverse alternating field electrophoresis. The genomic DNA of BKMF-1767 was resolved into 10 chromosomes ranging in size from 1.8-5.0 Mb, amounting to a total genome size of about 29 Mb. The genomic DNA of strain ME-446, on the other hand, was resolved into 11 chromosomes, amounting to a total genome size of about 32 Mb. Lignin peroxidase genes have been localized to five chromosomes in strain BKMF-1767 and to four chromosomes in strain ME-446. PMID- 8355608 TI - An M protein with a single C repeat prevents phagocytosis of Streptococcus pyogenes: use of a temperature-sensitive shuttle vector to deliver homologous sequences to the chromosome of S. pyogenes. AB - The major virulence factor of the important human pathogen Streptococcus pyogenes is the M protein, which prevents phagocytosis of the bacterium. In different strains of streptococci, there are over 80 serologically different M proteins and there are additional M-like proteins, some of which bind immunoglobulins. Although the sequence of the M molecules differs among different S. pyogenes strains, all M proteins, and some of the immunoglobulin-binding molecules, have at least two copies of the C repeat region. We describe construction of a deletion mutation in S. pyogenes, which has only one C repeat copy, and show that the mutant strain is still resistant to phagocytosis. The mutation was constructed in vitro and used to replace the resident emm allele in an S. pyogenes strain. To facilitate homologous recombination into the streptococcal chromosome, we adapted a shuttle vector which is temperature sensitive for replication in Gram-positive bacteria but not in Gram-negative hosts. This new method for delivery of a homologous DNA fragment to the S. pyogenes chromosome is efficient and reproducible and should be of general use. PMID- 8355609 TI - Sequence and analysis of the genetic locus responsible for surfactin synthesis in Bacillus subtilis. AB - The chromosomal region of Bacillus subtilis comprising the entire srfA operon, sfp and about four kilobases in between have been completely sequenced and functionally characterized. The srfA gene codes for three large subunits of surfactin synthetase, 402, 401 and 144 kDa, respectively, arranged in a series of seven amino acid activating domains which, as shown in the accompanying communication, recognize and bind the seven amino acids of the surfactin peptide. The srfA amino acid activating domains share homologies with similar domains of other peptide synthetases; in particular, regions can be identified which are more homologous in domains activating the same amino acid. A fourth gene in srfA encodes a polypeptide homologous to grsT. Four genes are positioned between srfA and sfp, the disruption of which does not affect surfactin biosynthesis. PMID- 8355610 TI - Characterization of the srfA locus of Bacillus subtilis: only the valine activating domain of srfA is involved in the establishment of genetic competence. AB - srfA is a locus required for the production of the lipopeptide antibiotic surfactin. This locus is also necessary for efficient sporulation and competence development. Mutations in the 5' portion of the srfA operon affect all three of these processes, whereas mutations in the 3' portion of srfA only affect sporulation and surfactin production. Analysis of the proteins encoded by the srfA locus revealed seven large domains which are likely to be responsible for the activation and binding of the seven amino acids of surfactin. Identification of the amino acid that is activated by the srfA domains was determined by amino acid-dependent pyrophosphate exchange reactions on partially purified cell extracts of strains carrying different srfA mutations. These results indicate colinearity between the order of the domains in the srfA locus and the amino acid sequence of surfactin. The minimal genetic element of srfA required for the establishment of competence was shown to be the 5' region of the second open reading of srfA, which encodes the valine activation domain. This portion of srfA, when cloned on a plasmid, complemented the competence deficiency of a srfA deletion mutant in trans. PMID- 8355611 TI - Identification of cpsD, a gene essential for type III capsule expression in group B streptococci. AB - We showed previously that a mutant strain of group B Streptococcus (GBS) defective in capsule production was avirulent. This study describes the derivation of an unencapsulated mutant from a highly encapsulated wild-type strain of type III GBS, COH1, by transposon mutagenesis with Tn916 delta E. The mutant, COH1-13, was sensitive to phagocytic killing by human leukocytes in vitro and was relatively avirulent in a neonatal rat sepsis model compared with the wild-type strain. No capsular polysaccharide was evident in the cytoplasm or on the cell surface of the mutant strain. The Tn916 delta E insertion site in COH1 13 was mapped to the same chromosomal location as the Tn916 insertion site in the unencapsulated type III mutant COH31-15 reported previously. Nucleotide sequencing of DNA flanking the insertion site in COH1-13 revealed an open reading frame, designated cpsD, with significant homology to the rfbP gene of Salmonella typhimurium. RfbP encodes a galactosyl transferase enzyme that catalyses the transfer of galactose to undecaprenol phosphate, the initial step in O polysaccharide synthesis. A particulate fraction of a lysate of wild-type strain GBS COH1 mediated the transfer of galactose from UDP-galactose to an endogenous acceptor. The galactose-acceptor complex partitioned into organic solvents, suggesting it is lipid in nature or membrane-associated. Galactosyl transferase activity was significantly reduced in the unencapsulated mutant strain COH1-13. These results, together with the similarity in deduced amino acid sequence between cpsD and rfbP suggest that cpsD encodes a galactosyl transferase essential for assembly of the GBS type III capsular polysaccharide. PMID- 8355612 TI - Proteins essential for expression of the Hms+ phenotype of Yersinia pestis. AB - One characteristic of pigmented (Pgm+) cells of Yersinia pestis is the adsorption of sufficient quantities of exogenous haemin during growth at 26 degrees C to form dark-brown colonies. Carriage of the cloned haemin-storage (hms) locus in pHMS1 restores this phenotype to spontaneous Pgm- chromosomal deletion mutants of Y. pestis. We have mapped the location of the structural genes for four proteins encoded on pHMS1 using minicell, in vitro transcription/translation, and complementation analysis. The hmsH and hmsF genes encode 90 kDa and 72 kDa protein precursors processed to surface-exposed, outer membrane proteins of 86 kDa and 70 kDa, respectively. Beta-galactosidase positive MudII1734 insertions in hmsR suggest that it encodes a protein that is also essential for haemin storage. Finally, the structural gene for a 41 kDa protein lies distal to the hmsH gene but, unlike hmsH, hmsF, and hmsR, its expression is not essential for the Hms+ phenotype in Y. pestis. PMID- 8355613 TI - Synthesis of the Escherichia coli K-12 nucleoid-associated DNA-binding protein H NS is subjected to growth-phase control and autoregulation. AB - Mutations in the structural gene (hns) for the Escherichia coli nucleoid associated DNA-binding protein H-NS cause highly pleiotropic effects on gene expression, site-specific recombination, transposition of phage Mu, the stability of the genetic material and the topological state of the DNA. We have investigated the regulation of hns expression and found that hns transcription is subjected to stationary phase induction and negative autoregulation. A set of hns lacZ protein and operon fusions was constructed in vitro and integrated in single copy into the attB site of the bacterial genome. Quantification of beta galactosidase activity along the bacterial growth curve showed that hns expression increases approximately 10-fold in stationary phase compared with exponentially growing cells. Immunological detection of the H-NS protein in growing and stationary phase cells supported the genetic data and showed that H NS synthesis varies with growth phase. In addition, primer extension experiments demonstrated that the amount of hns mRNA is elevated in stationary phase cultures and that hns transcription is directed by a unique promoter functioning in both log and stationary phase. Disruption of the hns gene by an insertion mutation led to the derepression (approximately fourfold) of the expression of an hns-lacZ operon fusion integrated at the attB site, showing that hns transcription is subjected to negative regulation by its own gene product. Autoregulation of hns expression is particularly pronounced in log phase. Both stationary phase control and autoregulation of hns transcription are associated with a 130 bp fragment that contains the hns promoter. In order to study the interaction of H-NS with its own regulatory region, we developed an efficient overproduction procedure and a simple purification scheme for H-NS. DNA gel retardation assays showed that the H-NS protein can preferentially interact with a restriction fragment carrying the hns promoter. This restriction fragment showed features of curved DNA as judged by two-dimensional polyacrylamide gel electrophoresis performed at 4 degrees C and 60 degrees C. PMID- 8355614 TI - The role of galE in the biosynthesis and function of gonococcal lipopolysaccharide. AB - Lipopolysaccharide is an essential component of the outer membrane of Gram negative bacteria and an important virulence factor of many pathogens, such as Neisseria gonorrhoeae. We have cloned the gonococcal galE gene which was found to be located in the gonococcal homologue of the meningococcal capsule gene complex region D. Sequence alignment indicated extensive homology with the Escherichia coli and Salmonella GalE proteins. Mutants with insertions in the galE gene were used as a tool to characterize the structure and function of gonococcal lipopolysaccharide. They displayed deep rough phenotypes, and chemical analysis confirmed the loss of galactose from the mutant lipopolysaccharide. Functional analysis indicated that the terminal oligosaccharides contain galactose and that these are lost in galE mutants. The importance of these oligosaccharides in gonococcal biology is clear from the fact that they contain the epitopes that are the targets for killing by normal human serum, and the acceptor site for sialic acid, which acts to protect the gonococcus from this killing. Furthermore, infection experiments in vitro indicate that the galE mutants exhibit unaltered intergonococcal adhesion as well as adhesion to, and invasion of, epithelial cells. PMID- 8355615 TI - Sequence, genetic, and lacZ fusion analyses of a nifR3-ntrB-ntrC operon in Rhodobacter capsulatus. AB - Transcription of Rhodobacter capsulatus genes encoding the nitrogenase polypeptides (nifHDK) is repressed by fixed nitrogen and oxygen. Regulatory genes required to sense and relay the nitrogen status of the cell are glnB, ntrB (nifR2), and ntrC (nifR1). R. capsulatus nifA1 and nifA2 require ntrC for activation when fixed nitrogen is limiting. The polypeptides encoded by nifA1 and nifA2 along with the alternate sigma factor RpoN activate nifHDK and the remaining nif genes in the absence of both fixed nitrogen and oxygen. In this study we report the sequence and genetic analysis of the previously identified nifR3-ntrB-ntrC regulatory locus. nifR3 is predicted to encode a 324-amino-acid protein with significant homology to an upstream open reading frame cotranscribed with the Escherichia coli regulatory gene, fis. Analysis of ntrC-lacZ fusions and complementation data indicate that nifR3 ntrBC constitute a single operon. nifR3 lacZ fusions are expressed only when lacZ is in the proper reading frame with the predicted nifR3 gene product. Tn5, a kanamycin-resistance cassette, and miniMu insertions in nifR3 are polar on ntrBC (required for nif transcription). This gene organization suggests that the nifR3 gene product may be involved in nitrogen regulation, although nifR3 is not stringently required for nitrogen fixation when ntrBC are present on a multicopy plasmid. In addition, a R. capsulatus strain with a 22-nucleotide insert in the chromosomal nifR3 gene was constructed. This nifR3 strain is able to fix nitrogen and activate nifA1 and nifA2 genes, again supporting the hypothesis that nifR3 is not stringently required for ntrC-dependent gene activation in R. capsulatus. PMID- 8355616 TI - Formation of a putative relaxation intermediate during T-DNA processing directed by the Agrobacterium tumefaciens VirD1,D2 endonuclease. AB - During the initial stages of crown gall tumorigenesis, the T-DNA region of the Agrobacterium tumefaciens Ti-plasmid is processed, resulting in the production of T-DNA molecules that are subsequently transferred to the plant cell. Processing of the T-DNA in the bacterium involves the nicking of T-DNA border sequences by an endonuclease encoded by the virD locus, and the subsequent tight (possibly covalent) association of the VirD2 protein with the 5' end of the processed single-stranded or double-stranded T-DNA molecule. To investigate the interaction of the VirD1,D2 endonuclease with a right T-DNA border, a set of plasmids containing both the border and virD sequences on the same high-copy-number replicon has been constructed and introduced into Escherichia coli. In this model system a tight nucleoprotein complex is formed between the relaxed double stranded substrate plasmid and the VirD2 protein. This putative T-DNA processing complex may be analogous to the covalent relaxation complex formed between the pilot protein and plasmid DNA during bacterial conjugation. VirD2 attachment to the relaxed substrate plasmid was resistant to denaturing agents but sensitive to S1 nuclease digestion, indicating a single-stranded region near the site of protein attachment. We speculate that this structure may be an intermediate formed prior to T-strand unwinding from the substrate plasmid in a host bacterium. PMID- 8355617 TI - Molecular cloning of a gene involved in glucose sensing in the yeast Saccharomyces cerevisiae. AB - Cells of the yeast Saccharomyces cerevisiae display a wide range of glucose induced regulatory phenomena, including glucose-induced activation of the RAS adenylate cyclase pathway and phosphatidylinositol turnover, rapid post translational effects on the activity of different enzymes as well as long-term effects at the transcriptional level. A gene called GGS1 (for General Glucose Sensor) that is apparently required for the glucose-induced regulatory effects and several ggs1 alleles (fdp1, byp1 and cif1) has been cloned and characterized. A GGS1 homologue is present in Methanobacterium thermoautotrophicum. Yeast ggs1 mutants are unable to grow on glucose or related readily fermentable sugars, apparently owing to unrestricted influx of sugar into glycolysis, resulting in its rapid deregulation. Levels of intracellular free glucose and metabolites measured over a period of a few minutes after addition of glucose to cells of a ggs1 delta strain are consistent with our previous suggestion of a functional interaction between a sugar transporter, a sugar kinase and the GGS1 gene product. Such a glucose-sensing system might both restrict the influx of glucose and activate several signal transduction pathways, leading to the wide range of glucose-induced regulatory phenomena. Deregulation of these pathways in ggs1 mutants might explain phenotypic defects observed in the absence of glucose, e.g. the inability of ggs1 diploids to sporulate. PMID- 8355618 TI - The importance of morphological events and intercellular interactions in the regulation of prespore-specific gene expression during sporulation in Bacillus subtilis. AB - We have established a time course for the early morphological events of sporulation in Bacillus subtilis and related this to changes in gene expression, particularly those occurring in the prespore compartment. We have also systematically studied the effects of mutations in various regulatory (spo) genes on prespore-specific gene expression. On the basis of these results, and those of other laboratories, at least four distinct temporal classes of prespore-specific gene expression can now be distinguished. The first class begins within 15 min of the formation of the spore septum, and requires the sigma F form of RNA polymerase. The second class, also directed by RNA polymerase containing sigma F, begins soon after the completion of prespore engulfment, and depends on an intercellular signal from the mother cell. This transcription results in synthesis of sigma G. However, sigma G activity, directing the third class of gene expression, appears only about 30 min later and is dependent on the completion of prespore engulfment and on further interactions with the mother cell. The fourth class of gene expression has been described. The results demonstrate that the prespore programme of gene expression incorporates a series of control points modulated by information from the mother cell and on progress through the morphogenetic process. PMID- 8355619 TI - Nucleotide substitutions and small-scale insertion produce size and antigenic variation in group A streptococcal M1 protein. AB - The presence of M protein on the surface of group A streptococci (GAS) confers the ability of the cell to resist phagocytosis in the absence of type-specific antibodies. It undergoes antigenic variation with more than 80 different serotypes having been defined. We have sequenced the M protein gene (emm1.1) from strain CS190 and present evidence that individual nucleotide substitutions are responsible for sequence variation in the N-terminal non-repeat region of emm1.1 and these substitutions have altered antibody recognition of opsonic epitopes. The N-terminal non-repeat domains of two other closely related strains, 71-155 and 76-088, were found to have sequence identical to emm1.1 with the addition of a 21 bp insert. This study provides the first evidence that nucleotide substitutions and small insertions are responsible for size and antigenic variation in the N-terminal non-repeat domain of the M protein of GAS. PMID- 8355620 TI - In vitro modification of human immunodeficiency virus type 1 (HIV-1) infectivity by the U937 cells. AB - The effect of host cell factors on infectivity of human immunodeficiency virus type 1 (HIV-1) was studied by infecting a monoblastoid cell line (U937) or a T cell line (MOLT-4) with a highly infective single clone of HIV-1 and comparing the infectivity of the produced viruses to different cell lines. Chronically infected U937 cells consistently produced viruses with minimal infectivity. This phenotypic change was host-dependent as the back-passage of the U937-produced low infective viruses into MOLT-4 cells resulted in regaining their original high infectivity. Southern and Northern blot analyses of the HIV-1 grown in U937 cells did not reveal any genomic difference between it and the virus grown it MOLT-4 cells. The radioimmunoprecipitation analysis of viral proteins showed that the HIV-1-infected U937 cells had a different pattern of envelope glycoproteins and core proteins, which well correlated with the low infectivity of the produced viruses. This experimental system using MOLT-4 and U937 cell lines would be useful to further explore host cell factor(s) which play an important role in the regulation of HIV-1 infectivity. PMID- 8355621 TI - Yersinia pseudotuberculosis in Italy. Attempted recovery from 37,666 samples. AB - From 1981 to 1991, 37,666 human, animal, food and environmental samples were cultured for Yersinia pseudotuberculosis using direct plating methods and/or cold enhancement techniques. Despite an intensive surveillance and adequate culture methods, Y. pseudotuberculosis was isolated from stools of 0.05% (5/9,720) of patients with acute enteritis, and alimentary tracts of 0.1% (10/6,849) of apparently healthy animals. No Y. pseudotuberculosis strains were recovered from stools of 4,726 health controls nor from the appendices (656), mesenteric lymph nodes (84), and stools (421) of 656 patients operated for suspected appendicitis. Of the 10,842 food and 4,368 environmental samples, none yielded positive cultures for Y. pseudotuberculosis. PMID- 8355622 TI - Similarity in nucleotide sequence of the gene encoding nontoxic component of botulinum toxin produced by toxigenic Clostridium butyricum strain BL6340 and Clostridium botulinum type E strain Mashike. AB - The complete nucleotide and deduced amino acid sequence of the nontoxic component of botulinum type E progenitor toxin is determined in recombinant plasmid pU9BUH containing about 6.0 kb HindIII fragment obtained from chromosomal DNA of Clostridium butyricum strain BL6340. The open reading frame (ORF) of this nontoxic component gene is composed of 3,486 nucleotide bases (1,162 amino acid residues). The molecular weight calculated from deduced amino acid residues is estimated 13,6810.1. The present study revealed that 33 nucleotide bases of 3,486 are different in the nontoxic component gene between C. butyricum strain BL6340 and C. botulinum type E strain Mashike. This corresponds to the difference of 17 amino acid residues in these nontoxic component. PMID- 8355623 TI - Studies on hemolytic action of a hemolysin produced by Vibrio mimicus. AB - Some properties and mechanism of action of a hemolysin (VMH) produced by an enteropathogenic Vibrio mimicus strain was examined. VMH was heat-labile and inhibited by addition of divalent cations, including Ca2+, Mg2+ and Mn2+. The hemolysis by VMH was inhibited by incubating with gangliosides, suggesting that the ganglioside was the binding site on the erythrocyte membrane for VMH. Existence of a galactose moiety on reducing end of the ganglioside molecule and a sialic acid on the galactose moiety was suggested to be important for the binding of VMH molecule. Colloid osmotic manner of the hemolysis by VMH was demonstrated. PMID- 8355624 TI - Identification and characterization of heat-stable enterotoxin II-producing Escherichia coli from patients with diarrhea. AB - Stock strains of Escherichia coli isolated from patients with traveller's diarrhea were examined for production of heat-stable enterotoxin II (STII). Of 400 strains examined, 3 were found to produce STII. The nucleotide sequence of the STII gene of these human strains was shown to be identical to that of porcine strains. Cultured cells of these strains induced fluid accumulation in ligated mouse intestinal loops and the activity was neutralized by anti-STII antiserum. These results suggest that STII-producing enterotoxigenic E. coli can cause human diarrhea. PMID- 8355625 TI - [The role of Bacillus thuringiensis in natural biocenoses]. AB - The results of the author's data and those from literature on ecology and genetic exchange of Bacillus thuringiensis strains have been analyzed in this brief review. It has been concluded that there is no strict confinement of B. thuringiensis strains of the particular serotypes to certain habitat and that the bacteriocinogenicity is of great importance in the intraspecies competition and stability of strains in nature. It has been emphasized that the plasmid conjugation process in B. thuringiensis can serve as a main factor of genetic variability to establish ecological placement of these bacteria. PMID- 8355626 TI - [Inhibitors of nucleic acid synthesis as a means of identifying the forms of DNA dependent DNA polymerases in Acholeplasma laidlawii PG-8 and of determining their functions]. AB - Antibiotics, inhibitors of nucleic acids' synthesis from the group of chromomycins (olivomycin of sodium salt), anthracyclines (carminomycin and doxorubicin) and streptonigrin (bruneomycin) have been studied for their effect on DNA synthesis in vitro performed by DNA polymerases (1st and 2nd forms) of Acholeplasma laidlawii PG-8. It has been stated that olivomycin inhibits the function of both the first and second forms of DNA polymerases in proportion to an increase of the antibiotic concentration in the medium. Carminomycin in the concentration of about 1 microgram/ml almost completely inhibited the activity of both DNA polymerases. However, doxorubicin also belonging to the group of anthracyclins completely inhibited the activity of the first form of DNA polymerase in the concentration of 1 microgram/ml and practically has no effect in the concentration up to 100 micrograms/ml on the activity of the second form possessing 3'-->5'-function. Streptonigrin also proved to be suitable for differentiate the forms of DNA polymerases and to determine their functions. The first form of DNA polymerase with 5'-->3'-polymerase and exonuclease functions was not sensitive by this antibiotic in the concentration of 1000 micrograms/ml, while the activity of the second form of DNA polymerase with 3'-->5'-exonuclease functions was fully inhibited by this concentration of the antibiotic in the medium. The combination of doxorhubicin and streptonigrin in the medium can be used to determine the form of DNA polymerases and to identify their 5'-->3'- or 3'-->5'-exonuclease function and for selectivity inhibition of the function of one or another DNA polymerase in the medium. PMID- 8355627 TI - D. K. Zabolotny Institute of Microbiology and Virology of the Academy of Sciences of the Ukraine (to the 65th anniversary of foundation). PMID- 8355628 TI - [The growth and sporulation of Bacillus subtilis under different aeration conditions]. AB - The dynamics of accumulation of Bacillus subtilis 39 cells and spores under different conditions of aeration has been studied. It is shown possible to intensify the process of growth, biomass accumulation and sporulation of bacteria using aeration conditions. The growth of cells of the studied bacilli proceeds under conditions of providing the culture with oxygen according to its real demands for the whole period of fermentation. The mathematical models have been obtained which connect the aeration conditions with the rate of biomass accumulation and sporulation of the studied bacteria. It has been stated that with an increase of aeration the yield of microbic cells, degree of using the substrate by them as well as the specific growth rate become higher. Intensive aeration 4.4 = 5.8 g O2/l.h promotes the creation of the most optimal conditions for the growth of bacteria. While deteriorating the aeration to 3.2 g O2/l.h and over, the specific growth rate and yield of viable cells decrease. The optimal conditions of air feed and medium agitation rate decrease the duration of fermentation exerting no effect on the final yield of biomass. It is shown that yield of biomass and spores depends on the growth phase. PMID- 8355629 TI - [The interaction of pathogenic microorganisms with the sorbent polymethylsiloxane]. AB - The method of electron microscopy has been used to study adhesion of the microbic cells of standard strains of Staphylococcus aureus, Escherichia coli and fungi of genus Candida on the organosilicon sorbent polymethylsiloxane (PMS) and medicamentous complex containing it. This complex contains furazolidone and metronidazole immobilized on silver ions-modified PMS. It is shown that the adhesion of microorganisms is accompanied by their destruction whose rate on pure PMS and medicamentous complex is different. Using experimental data the assumptions are advanced concerning the mechanism of the PMS interaction with Gram-positive and Gram-negative microorganisms as well as with fungi of genus Candida. PMID- 8355630 TI - [The use of the polymerase chain reaction method in studying the causative agents of diphtherial infection]. AB - A method for identification of genomic polymorphism of strains belonging to different biovars Corynebacterium diphtheriae has been described. The method is based on the polymerase chain reaction (PCR) using universal inter-species oligonucleotide primer N 45. Using this method 17 strains of C. diphtheria, isolated in the western region of Ukraine during epidemic activity in 1992, were studied. The study has shown high similarity of PCR patterns of toxicogenic and non-toxicogenic strains of both mitis and gravis biovars. It is supposed that the method will be used in molecular epidemiology to identify new pathogenic isolates from different regions and countries. PMID- 8355631 TI - [The physiological-biochemical properties of Klebsiella pneumoniae strains of different origins]. AB - While comparatively analyzing the properties of Klebsiella pneumoniae from three studied sources (patients, healthy people, environment), no reliable differences between the comparable strains have been revealed. No differences have been found in the toxin formation, hemagglutinating and antilysozymic activity, adhesivity and invasive properties as well as in the peculiarities of gas exchange, while growing on media with different nitrogen and carbon sources. The studied microorganisms differed only in antibiotic resistance: strains isolated from the environment were sensitive to antibiotics, whereas strains of human origin were resistant to them. PMID- 8355632 TI - [The bacteriological and immunological efficacy of biosporin in nonspecific ulcerative colitis]. AB - The results from examination of intestinal microflora and immune status in 75 patients with nonspecific ulcerative colitis with different degree of disease seriousness are presented. The deviations in the composition of normal microflora were primarily expressed in a decrease of the number of bifidobacteria. In 64.9% of patients the disease proceeded against the background of deficit of T-cellular immunity link. The sufficiently expressed bacteriological and immunological efficiency of complex therapy including preparation from spore-forming bacteria as a normalizer of microflora is shown. PMID- 8355633 TI - [The use of soil micromycetes for treating industrial sewage]. PMID- 8355634 TI - [The count and distribution of saprophytic bacteria and bacteria of the E. coli group in the water of Odessa Bay and the adjacent waters]. AB - The quantity and distribution of heterotrophic and enteric bacteria as indicators of the human activity influence on the marine ecosystem have been studied in water thickness of the Odessa Bay. It has been established that in the late autumn period the average quantity of heterotrophic bacteria in Bay waters is 6500 cells/ml and the number of the enteric ones--2400 cells/l. The spatial distribution of the heterotrophic bacterioplankton was mosaic and a tendency to decrease their quantity while moving away from the shore was not observed. This indicated the absence of the shore flow influence on the distribution of heterotrophic bacteria. On the contrary, the number of enteric bacteria significantly decreased with an increase of the distance from the shore, but on the greater part of the Bay they were absent at all. As to the vertical distribution of the heterotrophic bacteria quantity their maximum was in the water layer (0.5) below the surface, whereas the distribution of enteric bacteria did not correspond to this rule. Proceeding from the number of heterotrophic bacteria in the late autumn period waters of the Odessa Bay can be characterized as mesoeutrophic and according to the value of coli-index--as mesosaprobic ones. PMID- 8355635 TI - [The species composition of the micromycetes in feed and their role in animal kojic acid toxicosis]. AB - Microflora of more than 100 samples of different sorts of foodstuff (coarse fodder, grain forage, mixed fodder, premixes, silo, whole milk substitute etc.) selected in 1989-1992 in the period of mass diseases and death of animals in farms of Ukraine has been studied. It is shown that the amount of spore material included in lg of fodder, depends on the sort of feed substrate. Grains and grain forage (94.5 thou. spores in 1 g) occupy the first place in sporification with fungi; vetch-oat mixture and whole milk substitute (82-89 thou. spores)--the second place; mixed fodder granules and maize briquettes (79.5-66.5 thou. spores) -the third place; the latter are mixed fodder plants hay, cereals straw (11.8 43.5 thou. spores). Aspergillus mainly occurred on the concentrated forage, grain, grain forage, in less amount--in grass stand, cereals straw. Penicilli, fusari and other species of saprophytic fungi dominated on hay of natural meadows, on mixed fodder plants and cereals straw. It has been stated that the highest toxicity was typical of the fodder samples infected with Aspergillus strains producing kojic acid. Under conditions of our experiments out of 67 strains of genus Aspergillus kojic acid was synthesized by 48.6% of the total number of the tested fungus cultures. The greatest number of kojic acid producers was found among Aspergillus flavus isolates (56.8%) the less number--among A. fumigatus (36.7%). Kojic acid has been revealed to exert a pathological effect on the organism of different animal species. PMID- 8355636 TI - [The determination of tetanus antitoxin by the latex agglutination reaction]. AB - A new method to detect the protective value of antitetanic antibody in latex agglutination test (LAT) has been described. The new method is highly sensitive and fast, and requires no special equipment. The optimal conditions of sensibilization, latex types, test providing procedure have been selected. New LAT detects approximately 0.0015 IU antitoxin per ml. This method can be used to determine the state of immunization of population against tetanus and to detect the protective antibodies in production series of human and horse antitetanic immunoglobulins. PMID- 8355637 TI - [The modification of a nutrient medium for determining the toxigenicity of Corynebacterium diphtheriae]. AB - The nutrient medium has been developed on the basis of home components to determine toxigenicity of Corynebacterium diphtheriae using the biological method of diphtheria diagnosis. The advantage of the proposed nutrient medium is independence of delivers of commercial dry nutrient agar from Dagestan Research Institute of Nutrient Media. PMID- 8355638 TI - [Synchronization of bacterial division in rapid change of tryptone concentration]. AB - Rapid decrease from 1 to 0.4% or rapid increase from 0.4 to 15 in tryptone concentration caused synchronization of cell division in a culture of Escherichia coli. The effect was not observed for the mutants impaired in reception of taxis system AW-569 and AW-618. Maintenance of the constant concentration of serine prior to and after alteration in tryptone concentration prevented synchronization in wild-type strains J621 and AW-405. Based on the results obtained, it was inferred that reception of the change in the concentration of the substrates attractants is necessary for synchronization of bacterial cell division this way. PMID- 8355639 TI - Thalamic vacuolation in acute Wernicke's encephalopathy [corrected]. AB - Two patients with acute Wernicke's encephalopathy, with the diagnosis confirmed pathologically at autopsy, showed substantial vacuolation and neuronal degeneration in discrete nuclei of the thalamus. Thalamic vacuolation has not been described previously in acute Wernicke's encephalopathy. The use of frozen sections to minimize processing artifact was fundamental in demonstrating this pathology. The pathogenic mechanism underlying this change appears to be different to that seen in the more typical periventricular, mamillary body and brainstem lesions. We hypothesize that a specific neural pathway may be involved and suggest that this pathway could be the ascending nitric oxide-containing cholinergic pathway from the brainstem. PMID- 8355640 TI - Metabolic changes in axotomized fetal and early postnatal hamster facial motoneurons: an autoradiographic study. AB - The developing facial neurons of a series of hamsters ranging in age from the 14 day fetus to the 9 day postnatal were axotomized. Postoperative times were graded for each age so that the retrograde response could be observed before any significant amount of cell degeneration or death occurred. The incorporation of tritiated uridine was followed by the autoradiographic procedure. Although grain counts, relative to control values, were significantly reduced only in the axotomized fetus and at 24 hours postoperatively in 4-day postnatal animals, there was also a repression of isotopic incorporation in all the other axotomized animals. These results support data obtained from previous work with the hamsters which indicate that it is not until after the nerve cell nucleolus reaches full cytomorphic maturity (between 15 and 20 days postnatal age in hamster facial neurons) that the axotomized neurons respond with significantly increased incorporation levels of isotope over that of control neurons. PMID- 8355643 TI - [Reflections on the use of ultrasonic diagnosis in pediatrics]. PMID- 8355641 TI - Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. AB - Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were prepared from brain cortex, hippocampus and striatum. Hepatic encephalopathy was induced by a two-stage liver devascularization procedure and acute hyperammonemia by a prolonged ammonium acetate infusion; rabbits receiving a sodium-potassium-acetate infusion served as controls. In these animal models extracellular brain glutamate levels are known to be elevated. However no significant alterations in the number nor the affinity of the MK-801 binding sites of the NMDA receptors were found during acute liver failure and acute hyperammonemia. These findings suggest that the NMDA receptor population remains unaltered in experimental encephalopathy from acute liver failure and acute hyperammonemia, despite alterations in extracellular brain glutamate levels. PMID- 8355642 TI - Neuronal and glial marker proteins in encephalopathy associated with acute liver failure and acute hyperammonemia in the rabbit. AB - Neuronal and glial cell marker proteins were quantified in order to evaluate the possibility of increased proteolysis in the brain of rabbits with acute liver failure and acute hyperammonemia. Acute liver failure was induced by a two-stage devascularization procedure. Acute hyperammonemia was induced by a prolonged infusion of ammonium acetate, which simulates the plasma ammonia level in acute liver failure. Control animals received an infusion of sodium/potassium acetate. After development of severe encephalopathy, the animals were sacrificed (13.7 +/- 1.3 hours for rabbits with acute liver failure and 20.2 +/- 0.8 hours for rabbits with hyperammonemia) (x +/- S.E.M./n = 6) and their brains were dissected into cerebral cortex, hippocampus, cerebellum and brain stem. The total protein content and the concentrations of the neuronal cell marker proteins NSE (neuron specific enolase), NF68 and NF200 (68 kD and 200 kD neurofilament polypeptides) and the glial cell marker proteins GFAP (glial fibrillary acidic protein) and S 100 were determined. Total protein content was decreased in the brain stem in acute hyperammonemia only. The content of neuronal and glial cell markers was not affected in either of the two conditions. However, low molecular weight proteolytic fragments of the NF 68 kD polypeptide were observed in the hippocampus of three out of six animals in both experimental groups. No proteolytic degradation of GFAP was observed. The results show that, in experimental encephalopathy due to acute liver failure and acute hyperammonemia, no major changes occur in the marker proteins. The finding of proteolytic fragments of the NF68 polypeptide indicates that the neuronal population is affected prior to glial alterations. These findings are in agreement with the concept that acute hepatic encephalopathy is reversible and induces only slight structural changes. PMID- 8355644 TI - [Pulmonary complications after bone marrow transplantation]. AB - Pulmonary toxicity occurs in approximately 10 to 50% of patients undergoing bone marrow transplantation (BMT). Bacterial pneumonia very commonly affects patients within the first 6 months post-BMT. Etiologic factors include neutropenia and the presence of graft-versus-host disease (GVHD). Pulmonary fungal infections, due to candida and aspergillus, may develop in 16% of patients receiving BMT, with a high mortality rate, being about 80%. A prolonged neutropenia as well as GVHD and associated immunosuppressive treatments are important factors in predisposing a patient to develop fungal pneumonitis. Interstitial pneumonitis occurs in 10-40% of patients; herpes viruses are the most commonly documented cause, with cytomegalovirus (CMV) being the most common pathogen. No causative organism is identified in up to 60% of the cases. It is likely that some of these cases may result from drug or radiation toxicity. Lung shielding and fractionation of the dose have decreased the incidence of interstitial pneumonitis to less than 5%. Patients with GVHD are predisposed to lung infections because of the immunosuppression that accompanies GVHD and its treatment. In addition, GVHD itself appears to have a direct effect on pulmonary epithelium. Cultural and serologic studies as well as radiographic investigations and other diagnostic procedures (ie bronchoalveolar lavage) are needed for appropriate management of pulmonary complications. PMID- 8355645 TI - [The timing of the start of rehabilitative intervention with the newborn infant at neurological risk]. AB - The few studies related to the effect of the timing of intervention of high-risk infants, ie. early vs late, have produced equivocal results. The aim of this study was to investigate whether "critical periods" for intervention exist. Among the high-risk infants (previously assigned to one of 3 random samples), who achieved follow-up at 5 yrs of age, 36 received a prescribed intervention as soon in NICU (very early treatment group: ET Gr). The other 21 infants began to receive the treatment after discharge (postdischarge treatment group: PDT Gr.). The remaining 27 received only traditional care both during hospitalization and after discharge (control group: C Gr.). Treated infants both ET Gr. and PDT Gr., exhibit significantly better neurological status than control infants, as assessed by Touwen Neurological Examination. They also scored significantly higher at standard psychological tests and have a significantly lower incidence of developmental sequelae. Insteated not significant differences of any of the measured outcomes were found between the ET Gr. and the PDT Gr. Delay in initiating intervention does not appear to reduce the benefits. Recent advances in the field of the developmental psychology have resulted in some new understandings of the early human behavior and the role of learning experiences in the developmental processes. Although learned changes in behavior occur from the earliest 2 and 4 months, when major physiologic/maturational changes are occurring (Lipsitt, 1986). Our findings are in accordance with the above statement and suggest that the crucial period for intervention is in 2 to 4 first months of life. Further studies are needed to solve the many unanswered questions in this controversial filed. PMID- 8355646 TI - [Boutonneuse fever in childhood: a pathology often underdiagnosed. A report of 2 clinical cases]. PMID- 8355648 TI - Missouri State Medical Association. 1993-1994 membership directory. PMID- 8355647 TI - [The Simpson-Golabi-Behmel syndrome. The stages of a diagnostic procedure]. AB - We report on an Italian patient with growth excess, course face and normal psychomotor development, who had a diagnosis of Simpson-Golabi-Behmel. The clinical difference between this syndrome and lysosomal diseases and other syndromes with overgrowth is discussed. PMID- 8355649 TI - Isolation and characterization of genome-specific DNA sequences in Triticeae species. AB - Two contrasting genome-specific DNA sequences were isolated from Aegilops speltoides (wild goat grass) and Hordeum chilense (wild barley), each representing more than 1% of the genomes. These repetitive DNA fragments were identified as being genome-specific before cloning by genomic Southern hybridization (using total genomic DNA as a probe), and hence extensive screening of clones was not required. For each fragment, up to six recombinant plasmid clones were screened and about half were genome-specific. Clone pAesKB52 from Ae. speltoides was a 763 bp EcoRI fragment, physically organized in simple tandem repeats and shown to localize to sub-telomeric chromosome regions of species with the Triticeae S-genome by in situ hybridization to chromosomes. The sequence data showed an internal duplication of some 280 bp, which presumably occurred before sequence amplification and dispersion, perhaps by unequal crossing-over or reciprocal translocation. In situ hybridization showed that the sequence distribution varied between closely related (S-genome) species. Clone pHcKB6 was a 339 bp DraI fragment from H. chilense, also tandemly repeated but more variable; loss of the DraI site resulting in a ladder pattern in Southern blots which had little background smear. In situ hybridization showed that the tandem repeats were present as small clusters dispersed along all chromosome arms except at a few discrete regions including the centromeres and telomeres. The clone hybridized essentially specifically to the H-genome of H. chilense and hence was able to identify the origin of chromosomes in a H. chilense x Secale africanum hybrid by in situ hybridization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355650 TI - Characterization of the Nicotiana tabacum L. genome by molecular cytogenetics. AB - Nicotiana tabacum (2n = 48) is a natural amphidiploid with component genomes S and T. We used non-radioactive in situ hybridization to provide physical chromosome markers for N. tabacum, and to determine the extant species most similar to the S and T genomes. Chromosomes of the S genome hybridized strongly to biotinylated total DNA from N. sylvestris, and showed the same physical localization of a tandemly repeated DNA sequence, HRS 60.1, confirming the close relationship between the S genome and N. sylvestris. Results of dot blot and in situ hybridizations of N. tabacum DNA to biotinylated total genomic DNA from N. tomentosiformis and N. otophora suggested that the T genome may derive from an introgressive hybrid between these two species. Moreover, a comparison of nucleolus-organizing chromosomes revealed that the nucleolus organizer region (NOR) most strongly expressed in N. tabacum had a very similar counterpart in N. otophora. Three different N. tabacum genotypes each had up to 9 homozygous translocations between chromosomes of the S and T genomes. Such translocations, which were either unilateral or reciprocal, demonstrate that intergenomic transfer of DNA has occurred in the amphidiploid, possibly accounting for some results of previous genetic and molecular analyses. Molecular cytogenetics of N. tabacum has identified new chromosome markers, providing a basis for physical gene mapping and showing that the amphidiploid genome has diverged structurally from its ancestral components. PMID- 8355651 TI - Consequences of unique double-stranded breaks in yeast chromosomes: death or homozygosis. AB - We have developed a system in which a unique double-stranded break (DSB) can be introduced into a yeast chromosome during mitotic growth. The recognition site for the endonuclease I-SceI was inserted at different places in the yeast genome in haploid and diploid cells expressing this endonuclease. Induction of the break in haploids results in cell death if no intact copy of the cleaved region is present in the cell. If such a copy is provided on a plasmid, as an ectopic gene duplication, or on a homologous chromosome, the break can be repaired. Repair results in two identical copies in the genome of the locus which has been cut. We call this phenomenon homozygotization by reference to diploids heterozygous for the cut site in which repair leads to homozygosis at this site. We have compared the efficiencies of repair in the various topological situations examined, and conclude that some mechanism must search for regions of homology to both sides of the DSB and that repair is successful only if the homologies are provided by the same template molecule. PMID- 8355652 TI - Chromosome mapping in Alcaligenes eutrophus CH34. AB - Mutants and mobilizing plasmids were developed as genetic tools in Alcaligenes eutrophus CH34. In order to map the chromosome, spontaneous and ethyl methane sulphonate (EMS)-induced mutants (mostly auxotrophs) were isolated. Another source of mutants was provided by the phenomenon of temperature-induced mortality and mutagenesis that is observed at 37 degrees C and is characteristic of many metallotolerant strains of A. eutrophus. Plasmid pULB113 (RP4::miniMu) was used to map the available mutations. Twenty-five loci were ordered in a circular map. pMOL50, a rearranged derivative of plasmid pMOL28, which was obtained in a survivor at 37 degrees C and displayed chromosome mobilizing activity (Cma+), was also used to mobilize chromosomal markers: resulting linkages were stronger than with pULB113, allowing confirmation of the circularity of the A. eutrophus CH34 chromosome with a small number of crosses. PMID- 8355653 TI - Characterization of the ntrBC genes of Azospirillum brasilense Sp7: their involvement in the regulation of nitrogenase synthesis and activity. AB - A 7.1 kb EcoRI fragment from Azospirillum brasilense, that hybridized with a probe carrying the ntrBC genes from Bradyrhizobium japonicum, was cloned. The nucleotide sequence of a 3.8 kb subfragment was established. This led to the identification of two open reading frames, encoding polypeptides of 401 and 481 amino acids, that were similar to NtrB and NtrC, respectively. A broad host range plasmid containing the putative Azospirillum ntrC gene was shown to restore nitrogen fixation under free-living conditions to a ntrC-Tn5 mutant of Azorhizobium caulinodans. Several Tn5 insertion mutants were isolated in the ntrBC coding region in A brasilense. These mutants were prototrophic and Nif+. However, their nitrogenase activity was slightly lower than in the wild type and they were unable to grow on nitrate as sole nitrogen source. Under microaerobiosis and in the absence of ammonia, a nifA-lacZ fusion was expressed in the mutants at about 60% of the level in the wild type. In the presence of ammonia, the fusion was similarly expressed (60% of the maximum) both in the wild type and mutants. Addition of ammonia to a nitrogen-fixing culture of ntrBC mutants did not abolish nitrogenase activity, in contrast with the wild type. It thus appears that in Azospirillum the ntrBC genes are not essential for nitrogen fixation, although NtrC controls nifA expression to some extent. They are, however, required for the switch-off of nitrogenase activity. PMID- 8355654 TI - Sequence-specific binding of protein factors to two independent promoter regions of the acidic tobacco pathogenesis-related-1 protein gene (PR-1). AB - Gel shift mobility analysis, using the proximal 0.3 kb fragment of the tobacco pathogenesis-related protein 1a gene (PR-1a) and nuclear extracts from healthy Samsun NN tobacco leaves, which do not produce PR-1 proteins, showed a broad shifted signal with low mobility. This signal was not detected with nuclear proteins from the interspecific hybrid of Nicotiana glutinosa x Nicotiana debneyi, which constitutively produces the PR-1a protein. Similar shifted signals were detected with both proximal and distal regions of the 0.3 kb fragment using nuclear proteins from healthy Samsun NN tobacco, but not with proteins from the interspecific hybrid. Further experiments, performed using 5' or 3' truncated fragments of the 0.3 kb fragment, identified two independent binding sites: a distal site between -179 and -168 bp from the transcription start site, and a proximal site between -61 and -37 bp. Footprint analysis revealed two protected sequences, a distal region between -184 and -172 bp, and a proximal region between -68 and -51 bp. These results indicate the presence of regulatory factor(s) for expression of the acidic PR-1a gene. The possibility of negative regulation of the gene is discussed. PMID- 8355655 TI - Nitrate reductase of Neurospora crassa: the functional role of individual amino acids in the heme domain as examined by site-directed mutagenesis. AB - The enzyme nitrate reductase, which catalyzes the reduction of nitrate to nitrite, is a multi-redox center homodimeric protein. Each polypeptide subunit is approximately 100 kDa in size and contains three separate domains, one each for a flavin, a heme-iron, and a molybdopterin cofactor. The heme-iron domain of nitrate reductase has homology with the simple redox protein, cytochrome b5, whose crystal structure was used to predict a three-dimensional structure for the heme domain. Two histidine residues have been identified that appear to coordinate the iron of the heme moiety, while other residues may be important in the folding or the function of the heme pocket. Site-directed mutagenesis was employed to obtain mutants that encode nitrate reductase derivatives with eight different single amino acid substitutions within the heme domain, including the two central histidine residues. Replacement of one of these histidines by alanine resulted in a completely nonfunctional enzyme whereas replacement of the other histidine resulted in a stable and functional enzyme with a lower affinity for heme. Certain amino acid substitutions appeared to cause a rapid turnover of the heme domain, whereas other substitutions were tolerated and yielded a stable and fully active enzyme. Three different single amino acid replacements within the heme domain led to a dramatic change in regulation of nitrate reductase synthesis, with significant expression of the enzyme even in the absence of nitrate induction. PMID- 8355656 TI - Tissue- and stage-specific modulation of RNA editing of the psbF and psbL transcript from spinach plastids--a new regulatory mechanism? AB - The psbE operon of spinach chloroplasts, which includes the genes psbE, psbF, psbL and psbJ, encodes two RNA editing sites. One site corresponds to the initiation codon of the psbL transcript, as has been described earlier for the homologous transcript from tobacco, while at a second editing site, newly reported here, an internal phenylalanine codon of the psbF transcript is restored. Both these sites were investigated with respect to the extent of editing in spinach plastids at various developmental stages. The apparent existence of only completely edited transcripts in etioplasts and chloroplasts, indicates that light-induced processes are not acting as determinants in eliciting the editing process. Reduced editing is, however, observed in the psbF and psbL transcript from seeds and roots. This finding suggests that the RNA editing process is differentially down-regulated in leucoplasts and proplastids and that editing may, therefore, function as a regulatory device in plastid gene expression. PMID- 8355658 TI - Construction of a barley (Hordeum vulgare L.) YAC library and isolation of a Hor1 specific clone. AB - We have constructed an EcoRI-based YAC (yeast artificial chromosome) library from barley (Hordeum vulgare L. cv. Franka) using the vector pYAC4. The library consists of approximately 18,000 recombinant YACs with insert sizes ranging between 100 and 1000 kb (average of 160 kb) corresponding to 50% of the barley genome. Size fractionation after ligation resulted in an increased average insert size (av. 370 kb) but also in a substantial decrease in cloning efficiency. Less than 1% of the colonies showed homology to a plastome-specific probe; approximately 50% of the colonies displayed a signal with a dispersed, highly repetitive barley-specific probe. Using a primer combination deduced from the sequence of a member of the small Hor1 gene family coding for the C-hordein storage proteins, the library was screened by polymerase chain reaction and subsequently by the colony hybridization technique. A single YAC, designated Y66C11, with a 120 kb insert was isolated. This DNA fragment represents a coherent stretch from the terminal part of the Hor1 gene region as judged from the correspondence of the restriction patterns between Y66C11 DNA and barley DNA after hybridization with the Hor1-specific probe. Restriction with the isoschizomeric enzymes HpaII/MspI suggests a high degree of methylation of the Hor1 region in mesophyll cells but not in YAC-derived (yeast) DNA. PMID- 8355657 TI - Potentially rapid walking in cellular regulatory networks using the gene-gene interference method in yeast. AB - The recognition that cellular regulatory circuitry is composed of antagonistic elements has made possible a new approach to the selection of regulatory genes, called the gene-gene interference method. The method was used to identify and isolate genes possibly related in an antagonistic way to protein kinase A. Two such genes were recovered: ART1 encodes a potential regulator of cytokinesis and KAI1 appears to be involved in the Start control. The principles of the gene-gene interference method are discussed, as well as its possible general use for 'walking' within the cellular regulatory networks of eukaryotes. PMID- 8355659 TI - Extent of polytene in the pericentric heterochromatin of polytene chromosomes of pseudonurse cells of otu (ovarian tumor) mutants of Drosophila melanogaster. AB - In the polytene nuclei of germ-line cells (ovarian pseudonurse cells) of Drosophila melanogaster females mutant for otu11 (ovarian tumor), the pericentric heterochromatin is much more abundant than in somatic salivary gland cells. This is due to the degree of heterochromatin compaction (and consequently the level of underreplication) being lower in the nurse cells than in the salivary gland cells. The lower level of compaction probably results in a very low degree of position effect gene inactivation in the ovarian nurse cells. PMID- 8355660 TI - The gdhA1 point mutation in Escherichia coli K12 CLR207 alters a key lysine residue of glutamate dehydrogenase. AB - gdhA1 is a spontaneous mutant of Escherichia coli that causes complete loss of activity of the NADP-specific glutamate dehydrogenase (GDH) encoded by the gdhA gene. The gdhA1 mutational site has been identified by recombinational mapping, polymerase chain reaction (PCR) amplification and DNA sequencing, as an A to G transition at nucleotide 274 of the gdhA coding sequence, resulting in an amino acid change of lysine 92 to glutamic acid. The mutant enzyme forms hybrid hexamers with a wild-type GDH, providing a useful system for analysis of conformational integrity of mutational variants. PMID- 8355661 TI - Partial characterization of the Nicotiana tabacum actin gene family: evidence for pollen-specific expression of one of the gene family members. AB - The actin gene family of Nicotiana tabacum has been partially characterised by Southern hybridisation and by isolating lambda EMBL4 recombinants from a genomic library having homology to the soybean actin gene, Sac3. The number of actin genes with homology to Sac3 is estimated at between 20 to 30, based on Southern hybridisation and library screening, though the total gene family may be larger. Twenty-four recombinant lambda clones were isolated, 18 had unique restriction profiles and from these, 2 clones, Tac9 and Tac25, were selected for further study. The region of Tac25 hybridizing to Sac3 was sequenced and shown to contain an open reading frame (ORF) with homology to actin. Partial sequencing of Tac9 revealed a sequence with homology to the third exon of Tac25 and Sac3. The two tobacco actin sequences were compared to other reported actin gene sequences; Tac25 was closely related to the allelic potato actins, Pac58 and Pac85, while Tac9 was more related to Pac79 than to other plant actins. Northern hybridisation analysis showed that while Tac9 detected actin transcripts in RNA from root, leaf, stigma and pollen, Tac25 transcripts were only detected in pollen RNA. PMID- 8355663 TI - Selective enhancement of the interaction of curare with the nicotinic acetylcholine receptor. AB - Alteration of the ligand-binding domain of the nicotinic acetylcholine receptor through site-directed mutagenesis offers a powerful approach to the elucidation of structure-function relations in the receptor. Several conserved tyrosine residues in the large extracellular amino terminus of the alpha subunit of the receptor have been implicated by both chemical labeling and mutagenesis studies as playing an important role in the interaction of acetylcholine with the receptor. We and others have previously shown that substitution of phenylalanine for tyrosine at position 198 of the alpha subunit (alpha Y198F) leads to a rightward shift in the dose-response curve for acetylcholine-elicited currents. We have further investigated this particular mutation by examining the interaction of the competitive antagonist d-tubocurarine (curare) with the receptor. In contrast to the effect on the interaction of agonists with the receptor, this mutation leads to a marked increase in the affinity of the receptor for curare. Furthermore, this enhancement in affinity is selective for curare and is not seen with other competitive antagonists (pancuronium, beta erythroidine, and gallamine). Examination of the structures of these competitive antagonists leads to the proposal that this enhancement is due to the formation of an aromatic-aromatic interaction between the phenylalanine ring at position alpha 198 in the mutant and one of the aromatic rings of curare and that this can provide information about the spatial arrangement of this residue in the binding site. PMID- 8355664 TI - Heterogeneity of insulin receptors in rat tissues as detected with the partial agonist B29,B29'-suberoyl-insulin. AB - Using the insulin receptor partial agonist B29,B29'-suberoyl-insulin, a covalently dimerized insulin derivative, we previously demonstrated a heterogeneity of signal transduction by insulin receptors in two cell systems. The present study was designed to characterize the heterogeneity of insulin receptors in different rat tissues with this agent. Binding of 125I-insulin to insulin receptors and its inhibition by B29,B29'-suberoyl-insulin or by unlabeled insulin were assayed in plasma membranes from brain, spleen, adipocytes, and liver. IC50 values of B29,B29'-suberoyl-insulin were different in all tissues investigated (brain < spleen < adipocytes < liver). In contrast, IC50 values of insulin were identical, with the exception of spleen membranes (spleen < brain = adipocytes = liver). Furthermore, the IC50 ratios (B29 dimer/insulin) were significantly different, ranging from 0.7 (brain) to 12.8 (liver). Solubilization and partial purification of insulin receptors failed to abolish the marked difference between brain and liver (IC50 ratios of 1.8 and 7.1, respectively). The apparent molecular masses of the alpha subunits of insulin receptors, as labeled with a photoreactive insulin derivative, appeared identical in liver and spleen but were significantly lower in adipocytes and brain (liver = spleen > adipocytes > brain). The tissue-specific expression of the known insulin receptor isoforms generated by alternative splicing (insulin receptor types A and B), as assessed by polymerase chain reaction amplification with oligonucleotide primers flanking exon 11, was not correlated with the differences in the IC50 values and ratios for insulin and B29,B29'-suberoyl-insulin. Furthermore, IC50 values of both insulin and the B29 dimer were 3-fold lower in membranes from Rat1 cells overexpressing insulin receptor type A, compared with membranes with insulin receptor type B; the IC50 ratios were identical. No additional alternative splicing of insulin receptor mRNA was found by polymerase chain reaction amplification and digestion with HaeIII and AluI of seven overlapping domains of the receptor alpha subunit. These data suggest a heterogeneity of insulin receptors in rat tissues that is unrelated to alternative splicing of the insulin receptor gene. PMID- 8355662 TI - Inducibility of the SOS response in a recA730 or recA441 strain is restored by transformation with a new recA allele. AB - Escherichia coli RecA protein plays an essential role in both genetic recombination and SOS repair; in vitro RecA needs to bind ATP to promote both activities. Residue 264 is involved in this interaction; we have therefore created two new recA alleles, recA664 (Tyr264-->Glu) and recA665 (Tyr264-->His) bearing mutations at this site. As expected both mutations affected all RecA activities in vivo. Complementation experiments between these new alleles and wild-type recA or recA441 or recA730 alleles, both of which lead to constitutively activated RecA protein, were performed to further investigate the modulatory effects of these mutants on the regulation of SOS repair/recombination pathways. Our results provide further insight into the process of polymerization of RecA protein and its regulatory functions. PMID- 8355665 TI - Isolation and expression of a novel angiotensin II receptor from Xenopus laevis heart. AB - A Xenopus laevis heart cDNA library was screened using the human angiotensin type 1 (AT1) receptor cDNA coding sequence as a hybridization probe. A cDNA was isolated that encodes a protein of 363 amino acids that shares 63% sequence identity with the human AT1 receptor. Radioligand binding studies with the cloned receptor expressed in COS cells indicated that it is an angiotensin II receptor that possesses pharmacological properties distinct from those of the two known mammalian receptor subtypes, AT1 and AT2. Electrophysiological studies with the recombinant receptor expressed in X. laevis oocytes revealed that the amphibian receptor, like the mammalian AT1 receptor, can functionally couple to a second messenger system, leading to the mobilization of intracellular stores of calcium. However, nonpeptide antagonists selective for the mammalian AT1 and AT2 receptors do not block angiotensin II-stimulated functional responses in injected oocytes, which confirms that the amphibian receptor is a pharmacologically unique angiotensin II receptor. Nevertheless, based on conservation of structural features and motifs and similarity in coupling mechanisms, we speculate that the cloned Xenopus receptor is the amphibian counterpart of the mammalian AT1 receptor, having acquired its unique pharmacology as a consequence of evolutionary divergence. PMID- 8355666 TI - Identification and characterization of type A endothelin receptors in MMQ cells. AB - Recently the identification of endothelin (ET) receptors and ET in the pituitary gland has induced much interest in studying the potential role of ET in neuroendocrine regulation. MMQ, isolated from rat pituitary, is a prolactin secreting cell line. Similar to primary pituitary cells, the secretory response in MMQ cells is regulated by calcium and cAMP. In this report, by combining radioligand binding, cross-linking, and reverse transcription-polymerase chain reaction (RT-PCR) techniques, we characterized the properties of ET receptors in MMQ cells. 125I-ET-1 bound to membranes prepared from MMQ cells in a time dependent manner, reaching a plateau at 150 min at 25 degrees. 125I-ET-1 binding was inhibited by ET-1 with an IC50 value of 0.17 nM but was only partially (approximately 60%) inhibited by 1 microM ET-3. BQ123 (cyclo[D-Trp-D-Asp-Pro-D Val-Leu]) and FR139317 (cC6N-L-Leu-D-Trp-Me-D-2Pya-OH), two antagonists that are selective for the ETA receptor, inhibited 125I-ET-1 binding with IC50 values of 5 nM and 0.9 nM, respectively. RT-PCR detected mRNA for the ETA receptor but not the ETB receptor. RT-PCR detected mRNA for both ETA and ETB receptors in control experiments using rat kidney RNA. 125I-ET-1 binding was saturable, reaching a plateau at 0.1 nM. Scatchard analysis of the data from saturation studies yielded a straight line, with Bmax and Kd values of 0.11 pmol/mg and 0.038 nM, respectively. The number of receptors was 6.6 x 10(10) sites/mg of protein or 13,200 sites/cell. Cross-linking studies using bis(sulfosuccinimidyl)suberate revealed an apparent molecular mass of 65 kDa for the ET receptor. Labeling of the 65-kDa protein was abolished by ET-1, BQ123, or FR139317 at 0.1 microM. ET-1 stimulated the formation of total inositol phosphates in a dose-dependent manner, with an EC50 of 0.1 nM. The phosphatidylinositol hydrolysis response was also inhibited by BQ123 and FR139317. We conclude that MMQ cells express the ETA receptor, which is coupled to phosphatidylinositol hydrolysis. MMQ cells may be useful for elucidating the mechanisms through which ET exerts its regulatory effects on pituitary cells. PMID- 8355667 TI - Characterization of ligand and substrate specificity for the calcium-dependent and calcium-independent protein kinase C isozymes. AB - Analysis of [3H]phorbol-12,13-dibutyrate (PDBu) binding was performed with protein kinase C (PKC)-alpha, -beta 1, -gamma, -delta, -epsilon, -eta, and -zeta produced in Sf9 insect cells using the baculovirus expression system. With the exception of PKC-zeta, all of the PKC isozymes bound [3H]PDBu with high affinity (Kd < 1 nM), either in the presence or in the absence of calcium. Scatchard analysis using 100% phosphatidylserine vesicles revealed slightly lower affinity for the calcium-independent isozymes (PKC-delta, -epsilon, and -eta) than for the calcium-dependent isozymes (PKC-alpha, -beta, and -gamma). Competition for [3H]PDBu binding by different classes of PKC activators showed that 12 deoxyphorbol esters, mezerein, and octahydromezerein likewise possessed lower affinity for the calcium-independent isozymes. The mezerein analog thymeleatoxin was the most marked example, being almost 20-fold less potent for binding to PKC epsilon and -eta than to PKC-beta 1. In contrast, the indole alkaloids (-) indolactam V and (-)-octylindolactam V and the postulated endogenous activator 1,2-diacylglycerol bound with similar affinities to all of the PKC isoforms, suggesting that different residues/configurations in the binding sites of the different PKC isozymes might be involved in interaction with the pharmacophore of the activators. The seven PKC isozymes also showed clearly different substrate specificities with exogenous peptide and protein substrates. The heterogeneous behavior of the different members of the PKC family with ligands and substrates may contribute to the heterogeneity of PKC-mediated pathways at the cellular level. PMID- 8355668 TI - Functional effects of a naturally occurring amino acid substitution in human thymidylate synthase. AB - A major mechanism underlying the cytotoxicity of fluoropyrimidine analogs such as 5-fluorouracil and 5-fluoro-2'-deoxyuridine (FdUrd) occurs via the formation of 5 fluoro-2'-deoxyuridylate (FdUMP), a tight-binding inhibitor of thymidylate synthase (TS). Genetic variation in the structure of the TS molecule is an important determinant of response to fluoropyrimidines, because such variation may affect the binding of FdUMP to the enzyme. Previous studies have shown that the colonic tumor cell line HCT116 expresses two structurally distinct TS polypeptides that differ by the presence of tyrosine or histidine at residue 33. Compared with the Tyr-33 form, the His-33 form confers a 3-4-fold level of FdUrd resistance to cells; this was postulated to be derived from the reduced affinity of the enzyme for FdUMP and N5,N10-methylenetetrahydrofolate, ligands required for the formation of a stable inhibitory complex. In the present study, the Tyr 33 and His-33 forms have been purified to homogeneity, and their properties have been compared in detail. The Km values for dUMP and N5,N10 methylenetetrahydrofolate in the TS reaction were not significantly different between the two enzymes. In contrast, the catalytic efficiency (kcat) was 8-fold lower for the His-33 form. Kinetic and equilibrium binding measurements demonstrated that the dissociation constant for FdUMP binding into the ternary complex was 3-4-fold higher for the His-33 form; this was shown to be due to both a decrease in the rate of FdUMP association with the enzyme and an increase in the rate of FdUMP dissociation from the ternary complex. A TS form containing phenylalanine at residue 33 was created by site-directed mutagenesis and was shown to be very similar to the Tyr-33 enzyme with regard to kcat, pH/activity profile, and effect on FdUrd response. Thus, it is the presence of histidine at residue 33, rather than the absence of tyrosine, that is responsible for the alterations in catalytic and ligand-binding functions exhibited by the His-33 form. Possible mechanisms by which the histidine residue perturbs the structure of the TS active site are discussed. PMID- 8355669 TI - Phosphoramidon modulates the number of endothelin receptors in cultured Swiss 3T3 fibroblasts. AB - Endothelin (ET) is generated from prepro-ET by dibasic pair proteolysis, followed by specific proteolytic cleavage between Trp21 and Val22. Currently, intense research efforts are focused on the investigation of a metalloprotease-like ET converting enzyme that is inhibited by phosphoramidon but not by other inhibitors of neutral metalloproteases. In this report, we show that ET binding was increased significantly in cultured Swiss 3T3 fibroblasts after phosphoramidon treatment. Saturation studies using membranes prepared from cells or using intact cells assayed at 4 degrees showed that Bmax increased from 0.13 pmol/mg or 0.038 pmol/1 x 10(6) cells in untreated cells to 0.66 pmol/mg or 0.22 pmol/1 x 10(6) cells in cells treated with 100 microM phosphoramidon for 24 hr, equivalent to a net increase of 100,000 ET binding sites/cell. The effect of phosphoramidon was time and dose dependent. Other protease inhibitors, such as thiorphan, pepstatin A, E-64, phenylmethylsulfonyl fluoride, bestatin, and leupeptin, failed to exert a similar effect. Reverse phase high performance liquid chromatography analysis indicated that the effect of phosphoramidon was not due to inhibition of 125I-ET 1 degradation. The effect of phosphoramidon remained evident after cells were treated with actinomycin D or cycloheximide to inhibit protein synthesis, suggesting that the phenomenon was not due to the effect of phosphoramidon stimulating the synthesis of ET receptors. Degradation studies suggested that the effect of phosphoramidon was due to inhibition of a protease responsible for degrading the ET receptor. The fact that Swiss 3T3 cells treated with phosphoramidon exhibit an increase in the number of ET receptors is likely to complicate the interpretation of results when phosphoramidon or related compounds are used to block the putative ET-converting enzyme. PMID- 8355670 TI - Tityustoxin-K alpha, a structurally novel and highly potent K+ channel peptide toxin, interacts with the alpha-dendrotoxin binding site on the cloned Kv1.2 K+ channel. AB - The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-K alpha (TsTX-K alpha) and Dendroaspis angusticeps (snake) toxin dendrotoxin (alpha-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, alpha-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-K alpha produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-K alpha did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-K alpha blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-K alpha the blocking potency of alpha-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. alpha-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-K alpha, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-K alpha and alpha-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites. PMID- 8355671 TI - Long-lasting modification of the N-methyl-D-aspartate receptor channel by a voltage-dependent sulfhydryl redox process. AB - Ionic currents through the N-methyl-D-aspartate (NMDA) receptor channel are modulated by sulfhydryl redox reagents. We report here a novel form of redox modulation that alters NMDA channel kinetics in a voltage-dependent manner. The effects of the thiol reductant dithiothreitol (DTT) and the oxidizing agent 5,5' dithio-bis(2-nitrobenzoic acid) (DTNB) on NMDA-activated whole-cell currents were examined at various transmembrane voltages in cultured rat cortical neurons. DTT produced a similar level of potentiation of NMDA-induced currents at both -60 mV and +30 mV. However, the reversal of this potentiation by a sulfhydryl-oxidizing agent was dependent on the holding potential, because DTNB decreased the DTT potentiated NMDA responses more effectively at negative voltages. Interestingly, the NMDA peak current-voltage relationship became substantially outwardly rectifying when sequential DTT/DTNB treatments took place at a positive holding potential, but not under any other circumstances. Single-channel recordings from outside-out patches revealed that this phenomenon was likely produced by a significant and long-lasting 2.3-fold prolongation of the mean open time of NMDA channels at a positive holding potential. Thus, a voltage-dependent chemical alteration in NMDA receptor structure modified the kinetic properties of the associated ion channel. PMID- 8355672 TI - Development of lipoprotein-like lipid particles for drug targeting: neo-high density lipoproteins. AB - The possibility was explored of synthesizing, from commercially available lipids, high density lipoprotein (HDL)-like particles (neo-HDL) with the same physico chemical and biological properties as native HDL. A preparation method involving egg yolk phosphatidylcholine, cholesterol, and apoproteins from HDL led to the formation of particles with a composition, size, electrophoretic mobility, and density similar to those of discoidal HDL. In vitro experiments with isolated parenchymal liver cells showed that unlabeled HDL and neo-HDL competed for the same high affinity binding sites as did radiolabeled neo-HDL, whereas an excess of unlabeled low density lipoprotein was ineffective. In vivo experiments with radio-labeled neo-HDL indicated that neo-HDL showed a slow decay upon injection into rats, whereas the liver uptake did not exceed > 10% of the injected dose. The small additional liver uptake of radioactivity from neo-HDL, compared with HDL, was due to enhanced uptake by endothelial and Kupffer cells. Lactosylation of neo-HDL led to a markedly increased decay rate and a rapid uptake by rat liver (80% in 10 min). Parenchymal cells accounted for > 90% of the total liver uptake of radiolabeled lactosylated neo-HDL. Because the liver uptake of lactosylated 125I-neo-HDL could be blocked by preinjection of N-acetylgalactosamine, we conclude that the asialoglycoprotein receptor, which is specifically localized on parenchymal liver cells, is responsible for the avid liver uptake. With a fibroblast cell line transfected with the human asialoglycoprotein receptor, it was found that lactosylated neo-HDL binds with high affinity (Kd, 40 nM), in a galactose-specific way. It can be concluded that, with commercially available lipid components, HDL-like particles (neo-HDL) with virtually the same characteristics as found for native apolipoprotein E-free HDL can be reconstituted. Lactosylated neo-HDL, which is rapidly taken up by galactose specific receptors on parenchymal liver cells, might be used to transport antiviral drugs specifically to parenchymal liver cells. PMID- 8355673 TI - An E box mediates activation and repression of the acetylcholine receptor delta subunit gene during myogenesis. AB - The genes encoding the skeletal muscle acetylcholine receptor (AChR) are induced during muscle development and are regulated subsequently by innervation. Because both the initiation and the subsequent regulation of AChR expression are controlled by transcriptional mechanisms, an understanding of the steps that regulate AChR expression following innervation is likely to require knowledge of the pathway that activates AChR genes during myogenesis. Thus, we sought to identify the cis-acting sequences that regulate expression of the AChR delta subunit gene during muscle differentiation. We transfected muscle and nonmuscle cell lines with gene fusions between 5'-flanking DNA from the AChR delta-subunit gene and the human growth hormone gene, and we show here that 148 bp of 5' flanking DNA from the AChR delta-subunit gene contains two regulatory elements that control muscle-specific gene expression. One element is an E box, which is important both for activation of the delta-subunit gene in myotubes and for its repression in myoblasts and nonmuscle cells. Mutation of this E box, which prevents binding of MyoD-E2A and myogenin-E2A heterodimers, decreases expression in myotubes and increases expression in myoblasts and nonmuscle cells. An E-box binding activity, which does not contain MyoD, myogenin, or E2A proteins, is present in muscle and nonmuscle cells and may be responsible for repressing the delta-subunit gene in myoblasts and nonmuscle cells. An enhancer, which lacks E boxes, is also required for expression of the delta-subunit gene but does not confer muscle-specific expression. PMID- 8355674 TI - A small segment of the MAT alpha 1 transcript promotes mRNA decay in Saccharomyces cerevisiae: a stimulatory role for rare codons. AB - Differences in decay rates of eukaryotic transcripts can be determined by discrete sequence elements within mRNAs. Through the analysis of chimeric transcripts and internal deletions, we have identified a 65-nucleotide segment of the MAT alpha 1 mRNA coding region, termed the MAT alpha 1 instability element, that is sufficient to confer instability to a stable PGK1 reporter transcript and that accelerates turnover of the unstable MAT alpha 1 mRNA. This 65-nucleotide element is composed of two parts, one located within the 5' 33 nucleotides and the second located in the 3' 32 nucleotides. The first part, which can be functionally replaced by sequences containing rare codons, is unable to promote rapid decay by itself but can enhance the action of the 3' 32 nucleotides (positions 234 to 266 in the MAT alpha 1 mRNA) in accelerating turnover. A second portion of the MAT alpha 1 mRNA (nucleotides 265 to 290) is also sufficient to destabilize the PGK1 reporter transcript when positioned 3' of rare codons, suggesting that the 3' half of the MAT alpha 1 instability element is functionally reiterated within the MAT alpha 1 mRNA. The observation that rare codons are part of the 65-nucleotide MAT alpha 1 instability element suggests possible mechanisms through which translation and mRNA decay may be linked. PMID- 8355675 TI - Termination and pausing of RNA polymerase II downstream of yeast polyadenylation sites. AB - Little is known about the transcriptional events which occur downstream of polyadenylation sites. Although the polyadenylation site of a gene can be easily identified, it has been difficult to determine the site of transcription termination in vivo because of the rapid processing of pre-mRNAs. Using an in vitro approach, we have shown that sequences from the 3' ends of two different Saccharomyces cerevisiae genes, ADH2 and GAL7, direct transcription termination and/or polymerase pausing in yeast nuclear extracts. In the case of the ADH2 sequence, the RNA synthesized in vitro ends approximately 50 to 150 nucleotides downstream of the poly(A) site. This RNA is not polyadenylated and may represent the primary transcript. A similarly sized nonpolyadenylated [poly(A)-] transcript can be detected in vivo from the same transcriptional template. A GAL7 template also directs the in vitro synthesis of an RNA which extends a short distance past the poly(A) site. However, a significant amount of the GAL7 RNA is polyadenylated at or close to the in vivo poly(A) site. Mutations of GAL7 or ADH2 poly(A) signals prevent polyadenylation but do not affect the in vitro synthesis of the extended poly(A)- transcript. Since transcription of the mutant template continues through this region in vivo, it is likely that a strong RNA polymerase II pause site lies within the 3'-end sequences. Our data support the hypothesis that the coupling of this pause site to a functional polyadenylation signal results in transcription termination. PMID- 8355676 TI - Transgenic expression of COL1A1-chloramphenicol acetyltransferase fusion genes in bone: differential utilization of promoter elements in vivo and in cultured cells. AB - To directly compare the patterns of collagen promoter expression in cells and tissues, the activity of COL1A1 fusion genes in calvariae of neonatal transgenic mice and in primary bone cell cultures derived by sequential digestion of transgenic calvariae was measured. ColCAT3.6 contains 3.6 kb (positions -3521 to +115) of the rat COL1A1 gene ligated to the chloramphenicol acetyltransferase (CAT) reporter gene. ColCAT2.3 and ColCAT1.7 are 5' deletion mutants which contain 2,296 and 1,672 bp, respectively, of COL1A1 DNA upstream from the transcription start site. ColCAT3.6 activity was 4- to 6-fold lower in primary bone cell cultures than in intact calvariae, while ColCAT2.3 activity was at least 100-fold lower in primary bone cells than in calvariae. These changes were accompanied by a threefold decrease in collagen synthesis and COL1A1 mRNA levels in primary bone cells compared with collagen synthesis and COL1A1 mRNA levels in freshly isolated calvariae. ColCAT3.6 and ColCAT2.3 activity was maintained in calvariae cultured in the presence or absence of serum for 4 to 7 days. Thus, when bone cells are removed from their normal microenvironment, there is parallel downregulation of collagen synthesis, collagen mRNA levels, and ColCAT3.6 activity, with a much greater decrease in ColCAT2.3. These data suggest that a 624-bp region of the COL1A1 promoter between positions -2296 and -1672 is active in intact and cultured bone but inactive in cultured cells derived from the bone. We suggest that the downregulation of COL1A1 activity in primary bone cells may be due to the loss of cell shape or to alterations in cell-cell and/or cell matrix interactions that normally occur in intact bone. PMID- 8355677 TI - Functional domains of wild-type and mutant p53 proteins involved in transcriptional regulation, transdominant inhibition, and transformation suppression. AB - The wild-type (wt) p53 protein has transcriptional activation functions which may be linked to its tumor suppressor activity. Many mutant p53 proteins expressed in cancers have lost the ability to function as transcriptional activators and furthermore may inhibit wt p53 function. To study the mechanisms by which mutant forms of p53 have lost their transactivation function and can act in a dominant negative manner, a structure-function analysis of both mutant and engineered truncated forms of p53 was carried out. We show that different mutant p53 proteins found in cancers vary in the ability to inhibit the transcriptional transactivation and specific DNA binding activities of wt human p53. This transdominant effect was mediated through the carboxy-terminal oligomerization region. The role of the transactivation activity in transformation suppression by wt p53 was also examined by constructing an N-terminal deletion mutant lacking the transactivation domain. This mutant was unable to transactivate but could bind specifically to DNA. Although it was impaired in its ability to suppress transformation of primary rat embryo fibroblasts by adenovirus E1A plus activated ras, the N-terminal deletion mutant still had some suppression activity, suggesting that additional functions of p53 may contribute to transformation suppression. PMID- 8355678 TI - Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth. AB - We have characterized a growth factor-inducible gene, erp, and demonstrated that it encodes a 367-amino-acid nontransmembrane tyrosine phosphatase protein with significant similarity to the vaccinia virus H1 protein. Immunoprecipitation analyses show that the erp protein, ERP, is rapidly induced following serum stimulation of quiescent fibroblasts. ERP has been expressed as a fusion protein with glutathione S-transferase and shown to have tyrosine as well as serine protein phosphatase activity. The enzymatic activity of ERP depends on the presence of reducing agents such as dithiothreitol, and its tyrosine phosphatase activity is inhibited by sodium vanadate, a potent inhibitor of protein tyrosine phosphatases. The number of stable NIH 3T3 clones obtained after transfection with a vector expressing the complete ERP protein is reduced more than 90% compared with that after transfection with a vector expressing a mutated inactive ERP protein. The remaining ERP-expressing clones present a significant increase in the proportion of bi- and multinucleated cells and a decrease in proliferation rate. Studies on the genomic structure reveal that the erp transcription unit is 2.8 kbp long and split into four exons. The erp gene maps to the 17A2-17C region of the murine genome. Our results demonstrate that the protein product of the immediate-early gene erp has a negative effect on cell proliferation. PMID- 8355679 TI - Overlapping positive and negative regulatory elements determine lens-specific activity of the delta 1-crystallin enhancer. AB - Lens-specific expression of the delta 1-crystallin gene is governed by an enhancer in the third intron, and the 30-bp-long DC5 fragment was found to be responsible for eliciting the lens-specific activity. Mutational analysis of the DC5 fragment identified two contiguous, interdependent positive elements and a negative element which overlaps the 3'-located positive element. Previously identified ubiquitous factors delta EF1 bound to the negative element and repressed the enhancer activity in nonlens cells. Mutation and cotransfection analyses indicated the existence of an activator which counteracts the action of delta EF1 in lens cells, probably through binding site competition. We also found a group of nuclear factors, collectively called delta EF2, which bound to the 5' located positive element. delta EF2a and -b were the major species in lens cells, whereas delta EF2c and -d predominated in nonlens cells. These delta EF2 proteins probably cooperate with factors bound to the 3'-located element in activation in lens cells and repression in nonlens cells. delta EF2 proteins also bound to a promoter sequence of the gamma F-crystallin gene, suggesting that delta EF2 proteins are involved in lens-specific regulation of various crystallin classes. PMID- 8355680 TI - Inducible transcriptional activation of the human immunodeficiency virus long terminal repeat by protein kinase inhibitors. AB - The protein kinase inhibitor 2-aminopurine (2-AP) greatly stimulated expression in human promonocytes-macrophages of plasmid constructs carrying various reporter genes (chloramphenicol acetyltransferase, lacZ, firefly luciferase [luc], and Salmonella typhimurium histidinol dehydrogenase [his]) driven by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat. Adenine, adenosine, and caffeine were also effective inducers, but other purine or pyrimidine derivatives were ineffective. Experiments with mutant derivatives of the HIV-1 long terminal repeat revealed no specific eukaryotic promoter elements necessary for 2-AP induction but indicated the need for some minimum combination of such elements. Induction of HIV-1-directed gene expression appeared not to require action of the transcription factor NF-kappa B. The mechanism of induction was investigated by using the luc and his genes linked to the HIV-1 long terminal repeat. 2-AP induced marked, steady rises in mRNA accumulation from both transfected and chromosomally integrated HIV-1 constructs but no increases from an endogenous gene encoding gamma-actin or glucose 6-phosphate dehydrogenase. Thus, induction is selective and not an artifact induced by transfecting DNA into cells. In run-on transcription experiments, the rates of transcription initiation of both transfected and integrated copies of the his gene increased about sixfold in cells treated with 2-AP. Thus, while increased initiation accounted for a portion of 2-AP induction, it could not cause the far greater increase in steady state mRNA levels. 2-AP induction did not change mRNA decay rates and differed from the phorbol ester (phorbol myristate acetate)-induced activation of the protein kinase C-NF-kappa B pathway in its time course and in its requirement for new protein synthesis. Gel retardation assays showed that unlike phorbol myristate acetate induction, 2-AP induction is enhancer independent. Whereas many previous studies have implicated the activation of various protein kinases in gene induction, we here describe a mechanism of gene activation that appears to involve protein kinase inhibition as a component of the induction response. PMID- 8355681 TI - Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice. AB - DNA regions of 10 and 7 kb that flank the mouse metallothionein II (MT-II) and MT I genes, respectively, were combined with a minimally marked MT-I (MT-I*) gene and tested in transgenic mice. This construct resulted in (i) position independent expression of MT-I* mRNA and copy number-dependent expression, (ii) levels of hepatic MT-I mRNA per cell per transgene that were about half that derived from endogenous MT-I genes, (iii) appropriate regulation by metals and hormones, and (iv) tissue distribution of transgene mRNA that resembled that of endogenous MT-I mRNA. These features were not observed when MT-I* was tested without the flanking regions. These MT-I flanking sequences also improved the expression of rat growth hormone reporter genes, with or without introns, that were under the control of the MT-I promoter. Moreover, they enhanced expression from two of four heterologous promoters/enhancers that were tested. Deletion analysis indicated that regions known to have DNase I-hypersensitive sites were necessary but not sufficient for high-level expression. These data suggest that the DNA regions flanking the mouse MT-I and MT-II genes have functions like the locus control regions described for other genes. PMID- 8355682 TI - C/EBP, NF-kappa B, and c-Ets family members and transcriptional regulation of the cell-specific and inducible macrophage inflammatory protein 1 alpha immediate early gene. AB - Macrophage inflammatory protein 1 alpha (MIP-1 alpha) cytokine gene expression is restricted to a limited number of cells of hemopoietic origin and is rapidly and transiently induced by serum and endotoxin in macrophages. A single nuclear DNase I-hypersensitive site, which maps to the proximal promoter of the MIP-1 alpha gene, was identified in macrophage cells but was absent in cells which do not express basal levels of MIP-1 alpha mRNA. The proximal promoter sequences (+36 to -220 bp) are sufficient to confer cell-specific and inducible transcription in transfection assays. In vitro DNA-binding studies revealed five major nuclear protein binding sites in the proximal promoter which bind C/EBP, NF-kappa B, and/or c-Ets family members. Cell-specific differences in DNA binding by members of the NF-kappa B and c-Ets families correlate with the cell-specificity of MIP-1 alpha gene expression and the chromosomal conformation of the promoter. Changes in promoter binding by members of the C/EBP and NF-kappa B families correlate with the transcriptional up-regulation observed in serum- or endotoxin-stimulated macrophages in functional studies. PMID- 8355683 TI - Elements regulating an alternatively spliced exon of the rat fibronectin gene. AB - We have investigated the regulation of splicing of one of the alternatively spliced exons in the rat fibronectin gene, the EIIIB exon. This 273-nucleotide exon is excluded by some cells and included to various degrees by others. We find that EIIIB is intrinsically poorly spliced and that both its exon sequences and its splice sites contribute to its poor recognition. Therefore, cells which recognize the EIIIB exon must have mechanisms for improving its splicing. Furthermore, in order for EIIB to be regulated, a balance must exist between the EIIIB splice sites and those of its flanking exons. Although the intron upstream of EIIIB does not appear to play a role in the recognition of EIIIB for splicing, the intron downstream contains sequence elements which can promote EIIIB recognition in a cell-type-specific fashion. These elements are located an unusually long distance from the exon that they regulate, more than 518 nucleotides downstream from EIIIB, and may represent a novel mode of exon regulation. PMID- 8355684 TI - A unique ribonucleoprotein complex assembles preferentially on ecdysone responsive sites in Drosophila melanogaster. AB - The protein on ecdysone puffs (PEP) is associated preferentially with active ecdysone-inducible puffs on Drosophila polytene chromosomes and contains sequence motifs characteristic of transcription factors and RNA-binding proteins (S. A. Amero, S. C. R. Elgin, and A. L. Beyer, Genes Dev. 5:188-200, 1991). PEP is associated with RNA in vivo, as demonstrated here by the sensitivity of PEP specific chromosomal immunostaining in situ to RNase digestion and by the immunopurification of PEP in Drosophila cell extract with heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. As revealed by sequential immunostaining, PEP is found on a subset of chromosomal sites bound by the HRB (heterogeneous nuclear RNA-binding) proteins, which are basic Drosophila hnRNPs. These observations lead us to suggest that a unique, PEP-containing hnRNP complex assembles preferentially on the transcripts of ecdysone-regulated genes in Drosophila melanogaster presumably to expedite the transcription and/or processing of these transcripts. PMID- 8355685 TI - A phylogenetically conserved sequence within viral 3' untranslated RNA pseudoknots regulates translation. AB - Both the 68-base 5' leader (omega) and the 205-base 3' untranslated region (UTR) of tobacco mosaic virus (TMV) promote efficient translation. A 35-base region within omega is necessary and sufficient for the regulation. Within the 3' UTR, a 52-base region, composed of two RNA pseudoknots, is required for regulation. These pseudoknots are phylogenetically conserved among seven viruses from two different viral groups and one satellite virus. The pseudoknots contained significant conservation at the secondary and tertiary levels and at several positions at the primary sequence level. Mutational analysis of the sequences determined that the primary sequence in several conserved positions, particularly within the third pseudoknot, was essential for function. The higher-order structure of the pseudoknots was also required. Both the leader and the pseudoknot region were specifically recognized by, and competed for, the same proteins in extracts made from carrot cell suspension cells and wheat germ. Binding of the proteins is much stronger to omega than the pseudoknot region. Synergism was observed between the TMV 3' UTR and the cap and to a lesser extent between omega and the 3' UTR. The functional synergism and the protein binding data suggest that the cap, TMV 5' leader, and 3' UTR interact to establish an efficient level of translation. PMID- 8355686 TI - Identification of the ligand-binding regions in the macrophage colony-stimulating factor receptor extracellular domain. AB - The c-fms gene encodes the receptor for the macrophage colony-stimulating factor (M-CSF), and its extracellular domain consists of five immunoglobulin-like subdomains. To identify which of the five immunoglobulin-like regions are involved in ligand binding, we polymerase chain reaction-cloned five segments of the extracellular domain of the murine c-fms gene, each starting with the normal initiation codon and containing successive additions of the immunoglobulin-like subdomains. These protein segments are designated A, B, C, D, and E and contain, from the N-terminal end, either one, two, three, four, or all five immunoglobulin like subdomains, respectively. Each segment was expressed as a secreted soluble protein from a baculovirus expression vector in Sf9 insect cells. In addition, segments A, B, C, and E were produced as soluble alkaline phosphatase fusion proteins, as was a segment containing only the fourth and fifth immunoglobulin domains. These segments of the Fms extracellular domain were used to assess M-CSF binding by competition radioimmunoassays, plate binding immunoassays, and immunoprecipitation analyses. The results indicated that the first two N-terminal immunoglobulin-like domains did not interact with M-CSF but, in combination with the third immunoglobulin-like domain, provided high-affinity M-CSF binding. The fourth and fifth immunoglobulin-like domains near the cell membrane did not exhibit M-CSF binding and may inhibit interaction of M-CSF with the first three immunoglobulin domains. These results suggest that the three N-terminal immunoglobulin-like domains constitute the high-affinity M-CSF binding region and that the fourth and fifth immunoglobulin-like domains may perform functions other than ligand binding. PMID- 8355688 TI - Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding. AB - The DNA binding activity of the c-jun proto-oncogene product is inhibited by oxidation of a specific cysteine residue (Cys-252) in the DNA binding domain. Jun protein inactivated by oxidation of this residue can be efficiently reactivated by a factor from human cell nuclei, recently identified as a DNA repair enzyme (termed HAP1 or Ref-1). The HAP1 protein consists of a core domain, which is highly conserved in a family of prokaryotic and eukaryotic DNA repair enzymes, and a 61-amino-acid N-terminal domain absent from bacterial homologs such as Escherichia coli exonuclease III. The eukaryote-specific N-terminal domain was dispensable for the DNA repair functions of the HAP1 protein but was essential for reactivation of the DNA binding activity of oxidized Jun protein. Consistent with this finding, exonuclease III protein could not reactive Jun. A minimal 26 residue region of the N-terminal domain proximal to the core of the HAP1 enzyme was required for redox activity. By site-directed mutagenesis, cysteine 65 was identified as the redox active site in the HAP1 enzyme. In addition, it is proposed that cysteine 93 interacts with the redox active site, probably via disulfide bridge formation. It is concluded that the HAP1 protein has evolved a novel redox activation domain capable of regulating the DNA binding activity of a proto-oncogene product which is not essential for its DNA repair functions. Identification of a putative active site cysteine residue should facilitate analysis of the mechanism by which the HAP1 protein may alter the redox state of a wide range of transcription factors. PMID- 8355687 TI - cis-acting components in the replication origin from ribosomal DNA of Saccharomyces cerevisiae. AB - The ribosomal DNA (rDNA) repeats of Saccharomyces cerevisiae contain an autonomously replicating sequence (ARS) that colocalizes with a chromosomal origin of replication. We show that a minimal sequence necessary for full ARS function corresponds to a 107-bp rDNA fragment which contains three 10-of-11-bp matches to the ARS consensus sequence. Point mutations in only one of the 10-of 11-bp matches, GTTTAT GTTTT, inactivate the rDNA ARS, indicating that this consensus sequence is essential. A perfect match to a revised ARS consensus is present but not essential. Sequences up to 9 bp 5' from the essential consensus are dispensable. A broad DNA region directly 3' to the essential consensus is required and is easily unwound as indicated by: (i) hypersensitivity to nicking of an approximately 100-bp region by mung bean nuclease in a negatively supercoiled plasmid and (ii) helical instability determined by thermodynamic analysis of the nucleotide sequence. A correlation between DNA helical instability and replication efficiency of wild-type and mutated ribosomal ARS derivatives suggests that a broad region 3' to the essential ARS consensus functions as a DNA unwinding element. Certain point mutations that do not stabilize the DNA helix in the 3' region but reduce ARS efficiency reveal an element distinct from, but overlapping, the DNA unwinding element. The nucleotide sequence of the functionally important constituents in the ARS appears to be conserved among the rDNA repeats in the chromosome. PMID- 8355689 TI - The phylogenetically invariant ACAGAGA and AGC sequences of U6 small nuclear RNA are more tolerant of mutation in human cells than in Saccharomyces cerevisiae. AB - U6 small nuclear RNA (snRNA) is the most highly conserved of the five spliceosomal snRNAs that participate in nuclear mRNA splicing. The proposal that U6 snRNA plays a key catalytic role in splicing [D. Brow and C. Guthrie, Nature (London) 337:14-15, 1989] is supported by the phylogenetic conservation of U6, the sensitivity of U6 to mutation, cross-linking of U6 to the vicinity of the 5' splice site, and genetic evidence for extensive base pairing between U2 and U6 snRNAs. We chose to mutate the phylogenetically invariant 41-ACAGAGA-47 and 53 AGC-55 sequences of human U6 because certain point mutations within the homologous regions of Saccharomyces cerevisiae U6 selectively block the first or second step of mRNA splicing. We found that both sequences are more tolerant to mutation in human cells (assayed by transient expression in vivo) than in S. cerevisiae (assayed by effects on growth or in vitro splicing). These differences may reflect different rate-limiting steps in the particular assays used or differential reliance on redundant RNA-RNA or RNA-protein interactions. The ability of mutations in U6 nucleotides A-45 and A-53 to selectively block step 2 of splicing in S. cerevisiae had previously been construed as evidence that these residues might participate directly in the second chemical step of splicing; an indirect, structural role seems more likely because the equivalent mutations have no obvious phenotype in the human transient expression assay. PMID- 8355690 TI - Inactivation of YME1, a member of the ftsH-SEC18-PAS1-CDC48 family of putative ATPase-encoding genes, causes increased escape of DNA from mitochondria in Saccharomyces cerevisiae. AB - The yeast nuclear gene YME1 was one of six genes recently identified in a screen for mutations that elevate the rate at which DNA escapes from mitochondria and migrates to the nucleus. yme1 mutations, including a deletion, cause four known recessive phenotypes: an elevation in the rate at which copies of TRP1 and ARS1, integrated into the mitochondrial genome, escape to the nucleus; a heat-sensitive respiratory-growth defect; a cold-sensitive growth defect on rich glucose medium; and synthetic lethality in rho- (cytoplasmic petite) cells. The cloned YME1 gene complements all of these phenotypes. The gene product, Yme1p, is immunologically detectable as an 82-kDa protein present in mitochondria. Yme1p is a member of a family of homologous putative ATPases, including Sec18p, Pas1p, Cdc48p, TBP-1, and the FtsH protein. Yme1p is most similar to the Escherichia coli FtsH protein, an essential protein involved in septum formation during cell division. This observation suggests the hypothesis that Yme1p may play a role in mitochondrial fusion and/or division. PMID- 8355691 TI - The DNA-binding activity of the human heat shock transcription factor is regulated in vivo by hsp70. AB - The human heat shock transcription factor (HSF) is maintained in an inactive non DNA-binding form under nonstress conditions and acquires the ability to bind specifically to the heat shock promoter element in response to elevated temperatures or other conditions that disrupt protein structure. Here we show that constitutive overexpression of the major inducible heat shock protein, hsp70, in transfected human cells reduces the extent of HSF activation after a heat stress. HSF activation was inhibited more strongly in clones that express higher levels of hsp70. These results demonstrate that HSF activity is negatively regulated in vivo by hsp70 and suggest that the cell might sense elevated temperature as a decreased availability of hsp70. HSF activation in response to treatment with sodium arsenite or the proline analog azetidine was also depressed in hsp70-expressing cells relative to that in the nontransfected control cells. As well, the level of activated HSF decreased more rapidly in the hsp70 expressing clones when the cells were heat shocked and returned to 37 degrees C. These results suggest that hsp70 could play an active role in the conversion of HSF back to a conformation that does not bind the heat shock promoter element during the attenuation of the heat shock response. PMID- 8355692 TI - Nuclear protein-binding sites in a transcriptional control region of the rabbit alpha-globin gene. AB - The 5'-flanking and internal regions of the rabbit alpha-globin gene, which constitute a CpG island, are required for enhancer-independent expression in transfected cells. In this study, electrophoretic mobility shift assays revealed that a battery of nuclear proteins from both erythroid and nonerythroid cells bind specifically to these regulatory regions. Assays based on exonuclease III digestion, methylation interference, and DNase I footprinting identified sequences bound by proteins in crude nuclear extracts and by purified transcription factor Sp1. In the 5' flank, recognition sites for the transcription factors alpha-IRP (positions -53 to -44 relative to the cap site), CP1 (-73 to -69), and Sp1 (-95 to -90) are bound by proteins in K562 cell nuclear extracts, as are three extended upstream regions. Two recognition sites for Sp1 in intron 1 are also bound both by proteins in crude nuclear extracts and by purified Sp1. The sequences CCAC in intron 2 and C5 in the 3'-untranslated region also bind proteins. A major binding site found in exon 1, TATGGCGC, matches in sequence and methylation interference pattern the binding site for nuclear protein YY1, and binding is inhibited through competition by YY1-specific oligonucleotides. The protein-binding sites flanking and internal to the rabbit alpha-globin gene may form an extended promoter. PMID- 8355693 TI - Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA. AB - The fibroblast growth factor receptor 2 gene pre-mRNA can be spliced by using either the K-SAM exon or the BEK exon. The exon chosen has a profound influence on the ligand-binding specificity of the receptor obtained. Cells make a choice between the two alternative exons by controlling use of both exons. Using fibroblast growth factor receptor 2 minigenes, we have shown that in cells normally using the K-SAM exon, the BEK exon is not used efficiently even in the absence of the K-SAM exon. This is because these cells apparently express a titratable repressor of BEK exon use. In cells normally using the BEK exon, the K SAM exon is not used efficiently even in the absence of a functional BEK exon. Three purines in the K-SAM polypyrimidine tract are at least in part responsible for this, as their mutation to pyrimidines leads to efficient use of the K-SAM exon, while mutating the BEK polypyrimidine tract to include these purines stops BEK exon use. PMID- 8355694 TI - Genetic transfer and expression of reconstructed yeast artificial chromosomes containing normal and translocated BCL2 proto-oncogenes. AB - The goal of this study was to determine whether it will be feasible to study the expression of a large, human gene, such as the BCL2 proto-oncogene, by DNA transfection. The BCL2 proto-oncogene is 230 kb in size and is deregulated in tumor cells by translocation into the immunoglobulin heavy-chain locus. Yeast artificial chromosomes (YACs) containing the human BCL2 gene were altered by homologous recombination in Saccharomyces cerevisiae to yield replicas of the normal and translocated alleles. Constructions containing either allele and ranging in size from 360 to 800 kb were integrated stably into a mouse tumor line. Fifty-eight percent of the clones contained a copy of the entire YAC insert. Over 50% of these clones expressed appropriate levels of human BCL2 RNA and protein. These studies suggested that the expression of large human genes and their pathologic rearrangements can be studied by transfection techniques employing YACs propagated in S. cerevisiae. PMID- 8355695 TI - Selective DNA bending by a variety of bZIP proteins. AB - We have investigated DNA bending by bZIP family proteins that can bind to the AP 1 site. DNA bending is widespread, although not universal, among members of this family. Different bZIP protein dimers induced distinct DNA bends. The DNA bend angles ranged from virtually 0 to greater than 40 degrees as measured by phasing analysis and were oriented toward both the major and the minor grooves at the center of the AP-1 site. The DNA bends induced by the various heterodimeric complexes suggested that each component of the complex induced an independent DNA bend as previously shown for Fos and Jun. The Fos-related proteins Fra1 and Fra2 bent DNA in the same orientation as Fos but induced smaller DNA bend angles. ATF2 also bent DNA toward the minor groove in heterodimers formed with Fos, Fra2, and Jun. CREB and ATF1, which favor binding to the CRE site, did not induce significant DNA bending. Zta, which is a divergent member of the bZIP family, bent DNA toward the major groove. A variety of DNA structures can therefore be induced at the AP-1 site through combinatorial interactions between different bZIP family proteins. This diversity of DNA structures may contribute to regulatory specificity among the plethora of proteins that can bind to the AP-1 site. PMID- 8355696 TI - In vivo protein-DNA interactions at the c-jun promoter: preformed complexes mediate the UV response. AB - Irradiation of cells with UV light triggers a genetic response, called the UV response, which results in induction of a set of genes containing AP-1-binding sites. The c-jun gene itself, which codes for AP-1-binding activity, is strongly (> 100-fold) and rapidly activated by UV. The UV induction of c-jun is mediated by two UV response elements consisting of AP-1-like sequences within its 5' control region. We have analyzed protein-DNA interactions in vivo at the c-jun promoter in noninduced and UV-irradiated HeLa cells. In vivo footprint analysis was performed by using dimethyl sulfate on intact cells and DNase I on lysolecithihin-permeabilized cells in conjunction with ligation-mediated polymerase chain reaction to cover about 450 bp of the c-jun promoter, including the transcription start sites. We find that this region does not contain methylated cytosines and is thus a typical CpG island. In uninduced cells, in vivo protein-DNA interactions were localized to an AP-1-like sequence (nucleotides [nt] -71 to -64), a CCAAT box element (nt -91 to -87), two SP1 sequences (nt -115 to -110 and -123 to -118), a nuclear factor jun site (nt -140 to -132), and a second AP-1-like sequence (nt -190 to -183). These results indicate that complex protein-DNA interactions exist at the c-jun promoter prior to induction by an external stimulus. Surprisingly, after stimulation of c-jun expression by UV irradiation, all in vivo protein-DNA contacts remained essentially unchanged, including the two UV response elements located at the AP-1 like sequences. The UV-induced signalling cascade leads to phosphorylation of c Jun on serines 63 and 73 (Y. Devary, R.A. Gottlieb, T. Smeal, and M. Karin, Cell 71:1081-1091, 1992). Taken together, these data suggest that modification of the transactivating domain of DNA-bound c-Jun or a closely related factor may trigger the rapid induction of the c-jun gene. PMID- 8355697 TI - MPTP delta, a putative murine homolog of HPTP delta, is expressed in specialized regions of the brain and in the B-cell lineage. AB - Protein tyrosine phosphatases (PTPs), together with protein tyrosine kinases (PTKs), are involved in the regulation of cell activation, growth, and differentiation. To further elucidate the fine tuning of cell growth and differentiation through tyrosine phosphorylation, we tried to isolate mouse receptor-type PTP (RPTP) cDNA clones by screening mouse brain cDNA libraries with mouse CD45 PTP domain probes under reduced-stringency conditions. Characterization of isolated cDNA clones for RPTP showed that the cytoplasmic region contains two tandem repeats of PTP domain of about 230 amino acids with intrinsic phosphatase activity. The extracellular region was composed of immunoglobulin (Ig)-like domains and fibronectin type III (FN-III)-like domains. The gene was highly homologous to human PTP delta (HPTP delta) and thus was named MPTP delta (murine counterpart of HPTP delta). The MPTP delta gene appeared to generate at least three species of mRNA, which differ in the composition of the extracellular domain: type A, one Ig-like and four FN-III-like domains; type B, one Ig-like and eight FN-III-like domains; and type C, three Ig-like and eight FN III-like domains. Interestingly, the 5' untranslated region and the leader peptide of types A and B were completely different from those of type C. Northern (RNA) blot analysis demonstrated that brain, kidney, and heart cells express three mRNA species of about 7 kb. Antibody directed against part of the extracellular domain of type A MPTP delta recognized a 210-kDa protein in brain and kidney lysates. In situ hybridization of brain samples revealed that MPTP delta mRNA is present in the hippocampus, thalamic reticular nucleus, and piriform cortex, where some Src family PTKs have been also demonstrated to exist. Although MPTP delta mRNA was not detected in lymphoid tissues, all of the pre-B cell lines tested and one of three B-cell lines tested expressed MPTP delta mRNA, whereas antibody-producing B-cell hybridomas and T-cell and macrophage lines did not. Finally, the MPTP delta locus was tightly linked to the brown (b) locus on mouse chromosome 4. PMID- 8355698 TI - Identification and purification of a protein that binds DNA cooperatively with the yeast SWI5 protein. AB - The Saccharomyces cerevisiae SWI5 gene encodes a zinc finger protein required for the expression of the HO gene. A protein fusion between glutathione S-transferase and SWI5 was expressed in Escherichia coli and purified. The GST-SWI5 fusion protein formed only a low-affinity complex in vitro with the HO promoter, which was inhibited by low concentrations of nonspecific DNA. This result was surprising, since genetic evidence demonstrated that SWI5 functions at the HO promoter via this site in vivo. A yeast factor, GRF10 (also known as PHO2 and BAS2), that promoted high-affinity binding of SWI5 in the presence of a large excess of nonspecific carrier DNA was purified. Final purification of the 83-kDa GRF10 protein was achieved by cooperative interaction-based DNA affinity chromatography. In vitro binding studies demonstrated that SWI5 and GRF10 bind DNA cooperatively. Methylation interference and missing-nucleoside studies demonstrated that the two proteins bind at adjacent sites, with each protein making unique DNA contacts. SWI5 and GRF10 interactions were not detected in the absence of DNA. The role of cooperative DNA binding in determining promoter specificity of eukaryotic transcription factors is discussed. PMID- 8355699 TI - Demethylation of somatic and testis-specific histone H2A and H2B genes in F9 embryonal carcinoma cells. AB - In contrast to many other genes containing a CpG island, the testis-specific H2B (TH2B) histone gene exhibits tissue-specific methylation patterns in correlation with gene activity. Characterization of the methylation patterns within a 20-kb segment containing the TH2A and TH2B genes in comparison with that in a somatic histone cluster revealed that: (i) the germ cell-specific unmethylated domain of the TH2A and TH2B genes is defined as a small region surrounding the CpG islands of the TH2A and TH2B genes and (ii) somatic histone genes are unmethylated in both liver and germ cells, like other genes containing CpG islands, whereas flanking sequences are methylated. Transfection of in vitro-methylated TH2B, somatic H2B, and mouse metallothionein I constructs into F9 embryonal carcinoma cells revealed that the CpG islands of the TH2A and TH2B genes were demethylated like those of the somatic H2A and H2B genes and the metallothionein I gene. The demethylation of those CpG islands became significantly inefficient at a high number of integrated copies and a high density of methylated CpG dinucleotides. In contrast, three sites in the somatic histone cluster, of which two sites are located in the long terminal repeat of an endogenous retrovirus-like sequence, were efficiently demethylated even at a high copy number and a high density of methylated CpG dinucleotides. These results suggest two possible mechanisms for demethylation in F9 cells and methylation of CpG islands of the TH2A and TH2B genes at the postblastula stage during embryogenesis. PMID- 8355700 TI - Multiple proteins interact with the fushi tarazu proximal enhancer. AB - The expression of the Drosophila segmentation gene fushi tarazu (ftz) is controlled at the level of transcription. The proximal enhancer, located approximately 3.4 kb upstream of the transcription start site, directs lacZ fusion gene expression in a ftz-like seven-stripe pattern in transgenic fly embryos. We have taken a biochemical approach to identify DNA-binding proteins that regulate ftz gene expression through the proximal enhancer. DNase I footprinting and methylation interference experiments with staged Drosophila embryo nuclear extracts identified nine protein binding sites in the proximal enhancer. Ten different sequence-specific DNA-binding complexes that interact with eight of these sites were identified. Some interact with multiple sites, while others bind to single sites in the enhancer. Two of the complexes that interact with multiple sites appear to contain the previously described ftz regulators, FTZ-F1 and TTK/FTZ-F2. These in vitro studies allowed us to narrow down the proximal enhancer to a 323-bp DNA fragment that contains all of the protein binding sites. Expression directed by this minimal enhancer element in seven ftz-like stripes in transgenic embryos is identical to that directed by the full-length enhancer. Internal deletions of several sites abolish reporter gene expression in vivo. Thus, the ftz proximal enhancer, like other cell-type specific eukaryotic enhancers, interacts with an array of proteins that are expected to mediate the establishment, maintenance, and repression of transcription of the ftz gene in seven stripes in the developing embryo. PMID- 8355701 TI - Differentiation arrest and stromal cell-independent growth of murine erythroleukemia cells are associated with elevated expression of ets-related genes but not with mutation of p53. AB - The ELM erythroleukemia is novel in that long-term survival of leukemic cells in culture (ELM-D cells) is dependent on contact with a bone marrow-derived stromal feeder cell layer. However, a number of stroma-independent (ELM-I) mutants that vary in their ability to differentiate in vitro in response to erythropoietin and interleukin-3 have been derived. We have attempted to define the genetic changes responsible for these different phenotypes. At the p53 locus in the primary leukemic cells, one copy of the gene has been lost whereas the other contains an 18-bp depletion, implicating its mutation as an early step in the development of the leukemia. Changes in ets gene expression have also been found. The Fli-1 gene region is rearranged in the primary tumor because of the insertion of a retrovirus inserted upstream of one Fli-1 allele, but this does not result in Fli 1 gene activation in any of the ELM-D or ELM-I cell lines except one. It seems significant that this line is the only one to have lost the ability to differentiate in response to erythropoietin. In addition, up-regulation of erg is associated with stromal cell-independent growth, since all ELM-I mutants have moderate levels of erg mRNA, whereas only low or undetectable levels are found in primary leukemic cells in vivo or in ELM-D cells in vitro. This up-regulation of erg mRNA seems to be important for stromal cell-independent growth, since ELM-D cells show elevated expression of the erg gene after separation from stromal cells. This seems to be made permanent in ELM-I mutants, since they do not down regulate erg mRNA when grown in contact with stromal cells. We therefore propose that ets family members regulate both the survival and differentiation of erythroid cells. PMID- 8355703 TI - Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell specific subunit and evidence for an associated partner. AB - The human globin locus control region-binding protein, NF-E2, was purified by DNA affinity chromatography. Its tissue-specific component, p45 NF-E2, was cloned by use of a low-stringency library screen with murine p45 NF-E2 cDNA (N. C. Andrews, H. Erdjument-Bromage, M. B. Davidson, P. Tempst, and S. H. Orkin, Nature [London] 362:722-728, 1993). The human p45 NF-E2 gene was localized to chromosome 12q13 by fluorescent in situ hybridization. Human p45 NF-E2 and murine p45 NF-E2 are highly homologous basic region-leucine zipper (bZIP) proteins with identical DNA binding domains. Immunoprecipitation experiments demonstrated that p45 NF-E2 is associated in vivo with an 18-kDa protein (p18). Because bZIP proteins bind DNA as dimers, we infer that native NF-E2 must be a heterodimer of 45- and 18-kDa subunits. Although AP-1 and CREB copurified with NF-E2, no evidence was found for heterodimer formation between p45 NF-E2 and proteins other than p18. Thus, p18 appears to be the sole specific partner of p45 NF-E2 in erythroid cells. Cloning of human p45 NF-E2 should permit studies of the role of NF-E2 in globin gene regulation and erythroid differentiation. PMID- 8355702 TI - NonO, a non-POU-domain-containing, octamer-binding protein, is the mammalian homolog of Drosophila nonAdiss. AB - We have cloned the ubiquitous form of an octamer-binding, 60-kDa protein (NonO) that appears to be the mammalian equivalent of the Drosophila visual and courtship song behavior protein, no-on-transient A/dissonance (nonAdiss). A region unprecedently rich in aromatic amino acids containing two ribonuclear protein binding motifs is highly conserved between the two proteins. A ubiquitous form of NonO is present in all adult tissues, whereas lymphocytes and retina express unique forms of NonO mRNA. The ubiquitous form contains a potential helix turn-helix motif followed by a highly charged region but differs from prototypic octamer-binding factors by lacking the POU DNA-binding domain. In addition to its conventional octamer duplex-binding, NonO binds single-stranded DNA and RNA at a site independent of the duplex site. PMID- 8355704 TI - An mRNA-type intron is present in the Rhodotorula hasegawae U2 small nuclear RNA gene. AB - Splicing an mRNA precursor requires multiple factors involving five small nuclear RNA (snRNA) species called U1, U2, U4, U5, and U6. The presence of mRNA-type introns in the U6 snRNA genes of some yeasts led to the hypothesis that U6 snRNA may play a catalytic role in pre-mRNA splicing and that the U6 introns occurred through reverse splicing of an intron from an mRNA precursor into a catalytic site of U6 snRNA. We characterized the U2 snRNA gene of the yeast Rhodotorula hasegawae, which has four mRNA-type introns in the U6 snRNA gene, and found an mRNA-type intron of 60 bp. The intron of the U2 snRNA gene is present in the highly conserved region immediately downstream of the branch site recognition domain. Interestingly, we found that this region can form a novel base pairing with U6 snRNA. We discuss the possible implications of these findings for the mechanisms of intron acquisition and for the role of U2 snRNA in pre-mRNA splicing. PMID- 8355705 TI - A heterodimer of HEB and an E12-related protein interacts with the CD4 enhancer and regulates its activity in T-cell lines. AB - A T-lymphocyte-specific enhancer located 13 kb upstream of the murine CD4 gene was recently shown to be required for the developmentally regulated expression of CD4. We have previously identified three nuclear protein binding sites in this enhancer; one of these sites, CD4-3, is essential for expression and contains two E-box core motifs (CANNTG) adjacent to each other in the sequence TAACAGGTGTCAGCTGGT. In electrophoretic mobility shift assays using the CD4-3 oligonucleotide as a probe, three nuclear protein complexes, termed CD4-3A, -B, and -C, were detected with nuclear extracts from T-cell lines. CD4-3A, which involves nuclear protein binding to the 5' E-box, was detected only with nuclear extracts from lymphoid cells. Specific antisera were used to show that the CD4-3A complex contains a heterodimer or heterooligomer of basic helix-loop-helix transcriptional factors, E12 or a related factor and HEB, which is expressed predominantly in thymus. Consistent with this finding, in vitro-translated E12 and HEB proteins, as homodimers or heterodimers, bound preferentially to the 5' E box. Point mutations in the 5' E-box, but not in the 3' E-box, abolished CD4 enhancer activity. Furthermore, overexpression of Id, a protein that forms inactive heterodimers with E12/E47, blocked CD4 enhancer activity in T cells. These results suggest that a heterodimer composed of HEB and E12 or a closely related protein plays a critical role in CD4 enhancer function by interacting with the 5' E-box motif of the CD4-3 site in vivo. PMID- 8355706 TI - Saccharomyces cerevisiae HSP70 heat shock elements are functionally distinct. AB - The Saccharomyces cerevisiae HSP70 gene SSA1 has multiple heat shock elements (HSEs). To determine the significance of each of these sequences for expression of SSA1, we analyzed expression from a set of promoters containing point mutations in each of the HSEs, individually and in pairwise combinations. Of the three HSE-like sequences, two (HSE2 and HSE3) were active promoter elements; only one, HSE2, was active under basal growth conditions. Either HSE2 or HSE3 alone was able to drive SSA1 transcription at near-normal rates after heat shock. Both HSE2 and HSE3 were capable of driving basal transcription when placed in the context of the CYC1 promoter. Previous analysis had identified an upstream repressing sequence overlapping HSE2 that repressed basal transcription driven by HSE2. Our analysis showed that basal transcription driven by HSE3 was repressed both by the distant upstream repressing sequence and by closer flanking sequences. The ability to drive basal transcription is not inherent in all natural HSEs, since the HSEs from the heat-inducible SSA3 and SSA4 genes showed no basal activity when placed in the CYC1 vector. Gel mobility shift experiments showed that the same population of heat shock transcription factor molecules bound to HSEs capable of driving basal activity and to HSEs having very low or undetectable basal activity. PMID- 8355707 TI - Distinct properties of c-myc transcriptional elongation are revealed in Xenopus oocytes and mammalian cells and by template titration, 5,6-dichloro-1-beta-D ribofuranosylbenzimidazole (DRB), and promoter mutagenesis. AB - A block to c-myc transcription elongation has been observed in Xenopus oocytes and mammalian cells. Here, we show that the distribution of RNA polymerase II transcription complexes in the c-myc promoter proximal region in Xenopus oocytes is different from that observed previously in mammalian cells. Thus, there are major differences in the c-myc elongation block observed in the two systems. In addition, as first reported for a Xenopus tubulin gene (K. M. Middleton and G. T. Morgan, Mol. Cell. Biol. 10:727-735, 1990). c-myc template titration experiments reveal the existence of two classes of RNA polymerase II transcription complexes in oocytes: one (at low template concentration) that is capable of reading through downstream sites of premature termination, and another (high template concentration) that does not. We show that these classes of polymerases are distinct from those previously identified by 5,6-dichloro-1-beta-D ribofuranosylbenzimidazole (DRB), which distinguishes transcription complexes on the basis of transcribed distance, rather than on the basis of differential elongation through sites of premature termination. We also show that mutations that affect the efficiency of initiation of transcription from the c-myc P2 promoter can influence premature termination by at least two mechanisms: TATA box mutations function by the titration effect (decrease in transcription initiation results in a relative decrease in premature termination), while an upstream activator (E2F) site functions by contributing to the assembly of polymerase complexes competent to traverse the downstream sites of premature termination. PMID- 8355708 TI - The Ets-related transcription factor PU.1 immortalizes erythroblasts. AB - In vivo studies of Friend virus erythroleukemia have implied that proviral integrations adjacent to the gene for the Ets-related transcription factor PU.1 may inhibit the commitment of erythroblasts to differentiate and cause their capability for indefinite transplantation (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 62:4129-4135, 1988; R. Paul, S. Schuetze, S. L. Kozak, C. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test this hypothesis, we ligated PU.1 cDNA into a retroviral vector and studied its effects on cultured cells. Infection of fibroblasts with PU.1-encoding retrovirus resulted in PU.1 synthesis followed by nuclear pyknosis, cell rounding, and degeneration. In contrast, in long-term bone marrow cultures, erythroblasts were efficiently and rapidly immortalized. The resulting cell lines were polyclonal populations that contained PU.1, were morphologically blast-like, required erythropoietin and bone marrow stromal cells for survival and proliferation, and spontaneously differentiated at low frequency to synthesize hemoglobin. After 9 months in culture, erythroblasts became stroma independent, and they then grew as clonal cell lines. We conclude that PU.1 perturbs the pathway(s) that controls potential for indefinite proliferation and that it can be used to generate permanent erythroblast cell lines. PMID- 8355709 TI - Stimulation of kappa light-chain gene rearrangement by the immunoglobulin mu heavy chain in a pre-B-cell line. AB - B-lymphocyte development exhibits a characteristic order of immunoglobulin gene rearrangements. Previous work has led to the hypothesis that expression of the immunoglobulin mu heavy chain induces rearrangement activity at the kappa light chain locus. To examine this issue in more detail, we isolated five matched pairs of mu- and endogenously rearranged mu+ cell lines from the Abelson murine leukemia virus-transformed pro-B-cell line K.40. In four of the five mu+ cell lines, substantial expression of mu protein on the cell surface was observed, and this correlated with an enhanced frequency of kappa immunoglobulin gene rearrangement compared with that in the matched mu- cell lines. This increased kappa gene rearrangement frequency was not due to a general increase in the amount of V(D)J recombinase activity in the mu+ cells. Consistently, introduction of a functionally rearranged mu gene into one of the mu- pre-B-cell lines resulted in a fivefold increase in kappa gene rearrangements. In three of the four clonally matched pairs with increased kappa gene rearrangements, the increase in rearrangement frequency was not accompanied by a significant increase in germ line transcripts from the C kappa locus. However, in the fourth pair, K.40D, we observed an increase in germ line transcription of the kappa locus after expression of mu protein encoded by either an endogenously rearranged or a transfected functional heavy-chain allele. In these cells, the amount of the germ line C kappa transcript correlated with the measured frequency of rearranged kappa genes. These results support a regulated model of B-cell development in which mu protein expression in some way targets the V(D)J recombinase to the kappa gene locus. PMID- 8355710 TI - The ht beta gene encodes a novel CACCC box-binding protein that regulates T-cell receptor gene expression. AB - A gene encoding a novel CACCC box-binding protein that binds to the promoter region of the human T-cell receptor (TCR) V beta 8.1 gene and the mouse TCR alpha gene silencer has been cloned. This gene, termed ht beta, contains four zinc fingers of the class Cys2-X12-His2 that may be responsible for DNA binding and a highly negatively charged region that defines a putative transcriptional activation domain. Analysis of the expression of ht beta mRNA revealed similar expression levels and patterns in various cell lines. The bacterially expressed ht beta protein can bind to the CACCC box in both the human TCR V beta 8.1 gene promoter and the mouse TCR alpha gene silencer. The CACCC box is essential for efficient transcription of the V beta 8.1 promoter. Cotransfection with an ht beta expression plasmid and a reporter vector indicated that ht beta can activate human TCR V beta 8.1 gene transcription. ht beta also is able to counteract the silencing effect of the mouse TCR alpha gene silencer. The CACCC box has been found in almost all V beta 8.1 gene subfamily members and in both TCR alpha and beta gene enhancers in humans and mice. These results suggest that the CACCC box binding protein may have an important regulatory function for TCR gene expression in alpha beta T cells versus gamma delta T cells. PMID- 8355711 TI - Transcriptional regulator Leu3 of Saccharomyces cerevisiae: separation of activator and repressor functions. AB - The Leu3 protein of Saccharomyces cerevisiae binds to specific DNA sequences present in the 5' noncoding region of at least five RNA polymerase II-transcribed genes. Leu3 functions as a transcriptional activator only when the metabolic intermediate alpha-isopropylmalate is also present. In the absence of alpha isopropylmalate, Leu3 causes transcription to be repressed below basal levels. We show here that different portions of the Leu3 protein are responsible for activation and repression. Fusion of the 30 C-terminal residues of Leu3 to the DNA-binding domain of the Gal4 protein created a strong cross-species activator, demonstrating that the short C-terminal region is not only required but also sufficient for transcriptional activation. Using a recently developed Leu3 responsive in vitro transcription assay as a test system for repression (J. Sze, M. Woontner, J. Jaehning, and G. B. Kohlhaw, Science 258:1143-1145, 1992), we show that mutant forms of the Leu3 protein that lack the activation domain still function as repressors. The shortest repressor thus identified had only about 15% of the mass of the full-length Leu3 protein and was centered on the DNA-binding region of Leu3. Implications of this finding for the mechanism of repression are discussed. PMID- 8355712 TI - Repeated CT elements bound by zinc finger proteins control the absolute and relative activities of the two principal human c-myc promoters. AB - Transcription of the human proto-oncogene c-myc is governed by two tandem principal promoters, termed P1 and P2. In general, the downstream promoter, P2, is predominant, which is in contrast to the promoter occlusion phenomenon usually observed in genes containing tandem promoters. A shift in human c-myc promoter usage has been observed in some tumor cells and in certain physiological conditions. However, the mechanisms that regulate promoter usage are not well understood. The present studies identify regulators which are required to promote transcription from both human c-myc promoters, P1 and P2, and have a role in determining their relative activities in vivo. A novel regulatory region located 101 bp upstream of P1 was characterized and contains five tandem repeats of the consensus sequence CCCTCCCC (CT element). The integrity of the region containing all five elements is required to promote transcription from P1 and for maximal activity from P2 in vivo. A single copy of this same element, designated CT-I2, also appears in an inverted orientation 53 bp upstream of the P2 transcription start site. This element has an inhibitory effect on P1 transcription and is required for P2 transcription. The transcription factor Sp1 was identified as the factor that binds specifically to the tandem CT elements upstream of P1 and to the CT-I2 element upstream of P2. In addition, the recently cloned zinc finger protein ZF87, or MAZ, was also able to bind these same elements in vitro. The five tandem CT elements can be functionally replaced by a heterologous enhancer that only in the absence of CT-I2 reverses the promoter usage, similar to what is observed in the translocated c-myc allele of Burkitt's lymphoma cells. PMID- 8355713 TI - Saccharomyces cerevisiae BUF protein binds to sequences participating in DNA replication in addition to those mediating transcriptional repression (URS1) and activation. AB - The heteromeric BUF protein was originally shown to bind to URS1 elements which are situated upstream of many genes in Saccharomyces cerevisiae and mediate negative control of their transcription. Among the genes regulated through the URS1 site and the proteins interacting with it are those participating in carbon, nitrogen, and inositol metabolism; electron transport; meiosis; sporulation; and mating-type switching. We show here that pure BUF protein, in addition to binding to the negatively acting URS1 site, also binds to CAR1 sequences supporting transcriptional activation (upstream activation sequences). To determine the BUF protein structure, we cloned and sequenced the BUF1 and BUF2 genes and found them to be identical to the RF-A (RP-A) gene whose products participate in yeast DNA replication as single-stranded DNA binding proteins. These data argue that BUF protein-binding sites serve multiple roles in transcription and replication. PMID- 8355714 TI - Retention of fibroblast growth factor 3 in the Golgi complex may regulate its export from cells. AB - The fibroblast growth factors (FGFs) fall into two distinct groups with respect to their mode of release from cells. Whereas FGF1 and FGF2 lack conventional signal peptides, the remaining members have typical features of secreted proteins. However, the behavior of mouse FGF3 is anomalous, since, despite entering the secretory pathway and undergoing primary glycosylation, its release from transfected COS-1 cells is very inefficient compared with that of FGF4 and FGF5. To investigate the unusual properties of FGF3, we analyzed the processing, secretion, and intracellular localization of a series of site-directed mutants as well as chimeras produced by fusing parts of FGF3, FGF4, and FGF5. Wild-type FGF3 was shown to accumulate in an immature form in the Golgi complex, from where it is slowly released into the extracellular matrix. Removing or relocating the Asn linked glycosylation site further impaired its release, and exchanging the signal peptide or carboxy terminus had little effect. In contrast, a chimeric protein with an amino terminus from FGF5 was efficiently secreted and biologically active in cell transformation assays. The data suggest that a structural feature of FGF3 involving the amino-terminal region and glycosylation site has a significant bearing on its passage through the Golgi complex and may regulate the secretion of the ligand. PMID- 8355715 TI - SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase. AB - SPK1 was originally discovered in an immunoscreen for tyrosine-protein kinases in Saccharomyces cerevisiae. We have used biochemical and genetic techniques to investigate the function of this gene and its encoded protein. Hybridization of an SPK1 probe to an ordered genomic library showed that SPK1 is adjacent to PEP4 (chromosome XVI L). Sporulation of spk1/+ heterozygotes gave rise to spk1 spores that grew into microcolonies but could not be further propagated. These colonies were greatly enriched for budded cells, especially those with large buds. Similarly, eviction of CEN plasmids bearing SPK1 from cells with a chromosomal SPK1 disruption yielded viable cells with only low frequency. Spk1 protein was identified by immunoprecipitation and immunoblotting. It was associated with protein-Ser, Thr, and Tyr kinase activity in immune complex kinase assays. Spk1 was localized to the nucleus by immunofluorescence. The nucleotide sequence of the SPK1 5' noncoding region revealed that SPK1 contains two MluI cell cycle box elements. These elements confer S-phase-specific transcription to many genes involved in DNA synthesis. Northern (RNA) blotting of synchronized cells verified that the SPK1 transcript is coregulated with other MluI box-regulated genes. The SPK1 upstream region also includes a domain highly homologous to sequences involved in induction of RAD2 and other excision repair genes by agents that induce DNA damage. spk1 strains were hypersensitive to UV irradiation. Taken together, these findings indicate that SPK1 is a dual-specificity (Ser/Thr and Tyr) protein kinase that is essential for viability. The cell cycle-dependent transcription, presence of DNA damage-related sequences, requirement for UV resistance, and nuclear localization of Spk1 all link this gene to a crucial S phase-specific role, probably as a positive regulator of DNA synthesis. PMID- 8355716 TI - Functionally distinct elements are required for expression of the AMPD1 gene in myocytes. AB - AMP deaminase (AMPD) is an enzyme found in all eukaryotic cells. Tissue-specific and stage-specific isoforms of this enzyme are found in vertebrates, and expression of these different isoforms is determined by selective expression of the multiple genes. The AMPD1 gene is expressed predominantly in skeletal muscle, in which transcript abundance is controlled by stage-specific and fiber type specific signals. This enzyme activity is presumed to be important in skeletal muscle because a metabolic myopathy develops in individuals with an inherited deficiency of AMPD1. In the present study, cis- and trans-acting factors that control expression of AMPD1 have been identified. Two cis-acting elements located within 100 nucleotides of the transcriptional start site are required for muscle specific expression of AMPD1. One element (-100 to -79) behaves like a tissue specific enhancer, and it interacts with protein(s) found predominantly in nuclei of myoblasts and myotubes. This element is similar in sequence to an MEF2 binding motif, and it contains an A/T core that is essential for enhancer activity and binding of a nuclear protein(s). The second element (-60 to -40) has properties of a stage-specific promoter in that it is essential for muscle-specific expression of the AMPD1 promoter, does not confer muscle-specific expression on a heterologous promoter construct, and interacts with a protein(s) restricted to nuclei of differentiated myotubes. Interaction between these functionally distinct elements may be required for regulating the expression of AMPD1 during myocyte differentiation and in different muscle fiber types. PMID- 8355717 TI - Elements controlling follicular expression of the s36 chorion gene during Drosophila oogenesis. AB - An 84-bp proximal regulatory protein (PRR) of the Drosophila melanogaster s36 chorion gene is sufficient for directing proper temporal and spatial expression of a reporter gene in three domains of the follicle: anterior, posterior, and main body. Here we show that the fidelity of PRR-directed s36 expression is dependent on the proper dorsal-ventral differentiation of the follicular epithelium, which requires the Drosophila epidermal growth factor receptor homolog. Transgenic analysis of site-directed mutants of the PRR suggests that s36 expression is regulated by the concerted action of multiple positive activators. Several cis-acting transcriptional elements have been identified: some appear to function in a quantitative manner, while others either are essential or appear to regulate expression in particular spatial domains. The approximate locations of these regulatory elements have been defined; some map within sequences that are strongly conserved in widely divergent dipteran species. In fact, the PRR analog of the medfly Ceratitis capitata Ccs36 gene directs expression in a manner similar to the D. melanogaster s36 PRR. We propose a model for transcriptional regulation of s36 based on the prechoriogenic polarization of the follicular epithelium that surrounds the developing egg chamber. PMID- 8355719 TI - Femoral mononeuropathy induced by the lithotomy position: a report of 5 cases with a review of literature. AB - We report 5 young women who developed femoral mononeuropathy (FMN) after placement in the lithotomy position. Three had uncomplicated vaginal deliveries and 2 underwent exploratory laparoscopies. EMG was performed on 3 patients. The lesions were localized to the inguinal ligament and probably demyelinating, accounting for their excellent prognosis. On reviewing the literature, however, we believe that lithotomy position can cause FMN, not only by nerve compression at the inguinal ligament, but also by stretching of the nerve by excessive hip abduction and external rotation. PMID- 8355718 TI - In vitro transcription of a Drosophila U1 small nuclear RNA gene requires TATA box-binding protein and two proximal cis-acting elements with stringent spacing requirements. AB - Transcription of a Drosophila U1 small nuclear RNA gene was functionally analyzed in cell extracts derived from 0- to 12-h embryos. Two promoter elements essential for efficient initiation of transcription in vitro by RNA polymerase II were identified. The first, termed PSEA, is located between positions -41 and -61 relative to the transcription start site, is crucial for promoter activity, and is the dominant element for specifying the transcription initiation site. PSEA thus appears to be functionally homologous to the proximal sequence element of vertebrate small nuclear RNA genes. The second element, termed PSEB, is located at positions -25 to -32 and is required for an efficient level of transcription initiation because mutation of PSEB, or alteration of the spacing between PSEA and PSEB, severely reduced transcriptional activity relative to that of the wild type promoter. Although the PSEB sequence does not have any obvious sequence similarity to a TATA box, conversion of PSEB to the canonical TATA sequence dramatically increased the efficiency of the U1 promoter and simultaneously relieved the requirement for the upstream PSEA. Despite these effects, introduction of the TATA sequence into the U1 promoter had no effect on the choice of start site or on the RNA polymerase II specificity of the promoter. Finally, evidence is presented that the TATA box-binding protein is required for transcription from the wild-type U1 promoter as well as from the TATA-containing U1 promoter. PMID- 8355720 TI - Persistent and transient "conduction block" in motor neuron diseases. AB - Although conduction block indicates dysfunction of peripheral nerve, it may occur in patients with clinically typical motor neuron disease. There are no universally accepted criteria to identify conduction block, so diagnosis may be difficult. In some peripheral neuropathies, conduction block persists over long periods of time. If conduction block persists in motor neuron disease, then a more reproducible means for identification would be available. We repeatedly studied 9 patients with different forms of motor neuron diseases; conduction block was suspected because of excessive loss of the amplitude of motor evoked responses between distal and proximal stimulation sites. Five showed persistent amplitude loss at intervals between 12 and 36 months. All had focal loss of amplitude and area across a specific segment; all were men; none had definite upper motor neuron signs, 2 had probable and 3 had no upper motor neuron signs; 1 had IgM paraproteinemia, one elevated anti-GM1 titers; the duration of symptoms spanned 4-13 years. Four patients had transient loss of amplitude that was not reproduced in intervals between 3 and 13 months. None had focal loss of both amplitude and area; 2 were men; all had definite upper motor neuron signs and none had symptoms for more than 3-13 months; and none had immunological abnormalities. Thus, patients with persistent amplitude loss fulfill other criteria for conduction block, have prolonged survival but otherwise have clinical syndromes indistinguishable from ALS, except that definite upper motor neuron signs seem to be exceptional. PMID- 8355721 TI - Hereditary motor-sensory neuropathy and movement disorders. AB - To explore the relationship between hereditary motor and sensory neuropathy (HMSN) and movement disorders, we examined 7 patients with HMSN referred to our Movement Disorders Clinic and surveyed members of the Charcot-Marie-Tooth association. The following movement disorders were observed in the index patients: postural tremor in 6, rest tremor in 3, and Parkinsonism and dystonia in 2. Tremor, present in 40% of the 201 patients who responded to the survey, was first noted at a mean age of 36 years, and mostly involved the hands. Family history of tremor was more frequent in the tremor group (P < 0.005), which also had a significantly worse writing score than the nontremor group (P < 0.001). The overlap in clinical features between HMSN-associated tremor and essential tremor (ET), the high frequency of family history of tremor, and the lack of a relationship between the severity of tremor and of peripheral neuropathy suggest that the tremor in HMSN is pathogenically related to ET. PMID- 8355722 TI - Mechanisms of fatigue in normal intercostal muscle and muscle from patients with myasthenia gravis. AB - Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility. PMID- 8355723 TI - Na+ currents near and away from endplates on human fast and slow twitch muscle fibers. AB - Fast and slow twitch muscle fibers have distinct contractile properties. Here we determined that membrane excitability also varies with fiber type. Na+ currents (INa) were studied with the loose-patch voltage clamp technique on 29 histochemically classified human intercostal skeletal muscle fibers at the endplate border and > 200 microns from the endplate (extrajunctional). Fast and slow twitch fibers showed slow inactivation of endplate border and extrajunctional INa and had increased INa at the endplate border compared to extrajunctional membrane. The voltage dependencies of INa were similar on the endplate border and extrajunctional membrane, which suggests that both regions have physiologically similar channels. Fast twitch fibers had larger INa on the endplate border and extrajunctional membrane and manifest fast and slow inactivation of INa at more negative potentials than slow twitch fibers. For normal muscle, the differences between INa on fast and slow twitch fibers might: (1) enable fast twitch fibers to operate at high firing frequencies for brief periods; and (2) enable slow twitch fibers to operate at low firing frequencies for prolonged times. Disorders of skeletal membrane excitability, such as the periodic paralyses and myotonias, may impact fast and slow twitch fibers differently due to the distinctive Na+ channel properties of each fiber type. PMID- 8355724 TI - Sympathetic skin response abnormalities in amyotrophic lateral sclerosis. AB - The sympathetic skin response (SSR) was evaluated in 25 patients with amyotrophic lateral sclerosis (ALS) to assess for involvement of the autonomic nervous system. Twenty-two age-matched normals and 6 patients with muscular dystrophy served as controls. The SSR was intact in all normal volunteers and all patients with muscular dystrophy. The mean SSR latency in the ALS patients was prolonged compared to that of normals (2.29 +/- 0.28 versus 2.13 +/- 0.16 s, P < 0.05). The SSR was absent in one or both legs of 10 ALS patients (40%). Absence or abnormal latency of SSR in patients with ALS without clinical findings of autonomic failure suggests involvement of the autonomic nervous system in addition to the motor system. PMID- 8355725 TI - Chronic immune activation in the eosinophilia-myalgia syndrome. AB - Eosinophilia-myalgia syndrome (EMS) is a multisystem illness of uncertain pathogenesis that occurred in an epidemic related to the ingestion of contaminated L-tryptophan. To investigate the role of immune dysfunction in EMS we prospectively measured a serologic index of T-cell activation, the soluble interleukin-2 receptor (sIL-2R), in 7 patients followed into the late stages of the illness. As a group, EMS patients had significantly elevated sIL-2R levels throughout the study. Five patients suffered chronic symptoms of myalgia, arthralgia, muscle cramps, fatigue, or subjective memory impairment and all had persistently elevated sIL-2R levels. Two patients had near-resolution of EMS and normal sIL-2R levels. We conclude that chronic symptoms are common in EMS and are associated with persistent T-cell activation as measured by serum sIL-2R levels. These findings suggest that immunosuppressive treatment may be beneficial in EMS. PMID- 8355726 TI - Vocal cord paralysis: clinical and electrophysiologic features. AB - Vocal cord paralysis may occur in isolation or as part of a constellation of findings in neurological disease. We investigated the pathophysiology of these disorders with laryngeal electromyography (LEMG). We studied 44 patients with idiopathic vocal cord paralysis, confirmed by laryngoscopy. The major LEMG finding, present in 29 vocal cords, was evidence of active or chronic denervation in the thyroarytenoid (TA), indicating recurrent laryngeal neuropathy. Denervation of the cricothyroid (CT) in 5 patients indicated superior laryngeal neuropathy. TA and CT involvement in 1 patient indicated proximal laryngeal or vagus nerve damage. LEMG was performed in 48 patients with other laryngeal disorders. LEMG proved to be a safe and effective procedure in the diagnosis of laryngeal neuropathy as distinguished from supranuclear and mechanical disorders of the larynx. PMID- 8355727 TI - Increased spike-frequency adaptation and tea sensitivity in dorsal root fibers after sciatic nerve injury. AB - Excitability of rat dorsal root axons were studied 3 weeks after injury to the sciatic nerve. Whole nerve recordings were obtained from injured and control nerves in a sucrose gap chamber. Constant current depolarization pulses (30-200 ms) applied approximately 50% above the stimulus strength required for maximal amplitude compound action potentials (CAPs) evoked a burst of action potentials in the dorsal root which displayed spike adaptation. The depolarization-induced burst response of the dorsal roots was greatly reduced after crush or transection of the sciatic nerve. However, application of the potassium channel blocker, tetraethylammonium (TEA), restored the burst discharge in injured dorsal root axons. Brief tetanic stimulation of the dorsal root also induced an afterhyperpolarization (AHP) that was twice as large in the transection group as compared to the control group, and which was blocked by TEA. There were no changes seen in the amplitude of the compound action potential, frequency following characteristics, refractory properties, or 4-AP sensitivity in the dorsal roots after peripheral nerve injury. These results suggest that there is enhanced spike adaptation that occurs at the same time as an increase in the sensitivity to the potassium channel blocker, TEA, in axon regions proximal to the site of nerve injury and have implications for the pathophysiology of nerve injury. PMID- 8355728 TI - Quantifying how location and dose of botulinum toxin injections affect muscle paralysis. AB - Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effective paralysis. PMID- 8355730 TI - Use of laryngeal electromyography in prediction of recovery after vocal cord paralysis. PMID- 8355729 TI - Are nerve conduction studies useful for monitoring the adequacy of renal dialysis? AB - When hemodialysis was first used clinically, a peripheral neuropathy frequently emerged. The discovery that sufficient dialysis time would prevent the emergence of symptomatic neuropathy led to the routine use of nerve conduction studies (NCS) to monitor the "adequacy" of dialysis. Modern dialysis practice has evolved since then, and the patient population is markedly different. This report addresses the question of whether there is evidence to indicate that routine use of NCS is helpful to monitor the adequacy of present-day dialysis. A critical review of the available literature reveals that there is insufficient evidence to allow one to answer the question. PMID- 8355731 TI - Early involvement of motor nerve dysfunction in atypical cases with familial amyloidotic polyneuropathy (FAP) type I. PMID- 8355732 TI - Marfan's syndrome in association with cervical rib syndrome. PMID- 8355733 TI - In vivo and in vitro muscle tensions in wobbler mouse motor neuron disease. PMID- 8355734 TI - Intrapontine generation of myokymia in multiple sclerosis. PMID- 8355735 TI - Kineceptic ankle-foot orthosis in neuromuscular disease. PMID- 8355736 TI - Tuberculosis of striated muscle. PMID- 8355737 TI - Serial measurements of nerve conduction velocity and F-wave latency in diphtheritic neuropathy. PMID- 8355738 TI - Lambert-Eaton myasthenic syndrome associated with an ameloblastoma of the tibia. PMID- 8355739 TI - Macro-EMG and motor unit recruitment threshold. PMID- 8355740 TI - Effect of prenatal ultrasound screening on perinatal outcome. RADIUS Study Group. AB - BACKGROUND: Many clinicians advocate routine ultrasound screening during pregnancy to detect congenital anomalies, multiple-gestation pregnancies, fetal growth disorders, placental abnormalities, and errors in the estimation of gestational age. However, it is not known whether the detection of these conditions through screening leads to interventions that improve perinatal outcome. METHODS: We conducted a randomized trial involving 15,151 pregnant women at low risk for perinatal problems to determine whether ultrasound screening decreased the frequency of adverse perinatal outcomes. The women randomly assigned to the ultrasound-screening group underwent one sonographic examination at 15 to 22 weeks of gestation and another at 31 to 35 weeks. The women in the control group underwent ultrasonography only for medical indications, as identified by their physicians. Adverse perinatal outcome was defined as fetal death, neonatal death, or neonatal morbidity such as intraventricular hemorrhage. RESULTS: The mean numbers of sonograms obtained per woman in the ultrasound screening and control groups were 2.2 and 0.6, respectively. The rate of adverse perinatal outcome was 5.0 percent among the infants of the women in the ultrasound-screening group and 4.9 percent among the infants of the women in the control group (relative risk, 1.0; 95 percent confidence interval, 0.9 to 1.2; P = 0.85). The rates of preterm delivery and the distribution of birth weights were nearly identical in the two groups. The ultrasonographic detection of congenital anomalies had no effect on perinatal outcome. There were no significant differences between the groups in perinatal outcome in the subgroups of women with post-date pregnancies, multiple-gestation pregnancies, or infants who were small for gestational age. CONCLUSIONS: Screening ultrasonography did not improve perinatal outcome as compared with the selective use of ultrasonography on the basis of clinician judgment. PMID- 8355741 TI - Reversibility of unawareness of hypoglycemia in patients with insulinomas. AB - BACKGROUND: A lack of appropriate autonomic warning symptoms before the development of neuroglycopenia occurs frequently in patients with diabetes mellitus. The pathogenesis of this phenomenon is unclear, but it is associated with intensive insulin therapy, prolonged duration of diabetes, frequent episodes of hypoglycemia, and impaired glucose counterregulation. Recently, it has been proposed that repeated episodes of hypoglycemia may themselves induce the phenomenon. METHODS: To test this hypothesis and to determine whether the phenomenon is reversible, we assessed autonomic and neuroglycopenic symptoms, counterregulatory hormonal responses, and cognitive function during stepped hypoglycemic-clamp studies in 6 patients with insulinomas before and approximately six months after curative surgery and in 14 normal subjects matched for age, weight, and sex. RESULTS: Before surgery, the patients with insulinomas had lower scores than the normal subjects for autonomic symptoms (mean [+/- SD], 3.5 +/- 0.8 vs. 9.6 +/- 4.5) and neuroglycopenic symptoms (2.8 +/- 1.5 vs. 8.9 +/ 5.3). The patients also had impaired counterregulatory hormonal responses (their plasma epinephrine, norepinephrine, glucagon, growth hormone, and cortisol responses before surgery were 187 +/- 227 pg per milliliter [1.03 +/- 1.25 nmol per liter], 223 +/- 85 pg per milliliter [1.32 +/- 0.50 nmol per liter], 86 +/- 21 ng per liter, 7.4 +/- 5.2 micrograms per liter, and 12.1 +/- 1.5 micrograms per deciliter [334 +/- 41 nmol per liter], respectively, as compared with 842 +/- 439 pg per milliliter [4.63 +/- 2.41 nmol per liter], 519 +/- 150 pg per milliliter [3.07 +/- 0.89 nmol per liter], 201 +/- 58 ng per liter, 25.3 +/- 13.7 micrograms per liter, and 26.3 +/- 1.2 micrograms per deciliter [726 +/- 33 nmol per liter] in the normal subjects) and less deterioration in cognitive function than the normal subjects during hypoglycemia (sum of z scores for seven tests of cognitive function, 1.7 +/- 1.9 vs. 8.9 +/- 3.5) (P < 0.02 for all comparisons). Surgical cure reversed all these abnormalities (P not significant for all comparisons with the normal subjects). CONCLUSIONS: Hypoglycemia itself can induce unawareness of the autonomic and neuroglycopenic symptoms of hypoglycemia and decrease the counterregulatory hormonal responses to hypoglycemia. PMID- 8355742 TI - Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. AB - BACKGROUND: Patients with homozygous beta-thalassemia, who have a good prognosis during treatment with conventional therapy, appear to have an especially high probability of hematologic cure with bone marrow transplantation, although the morbidity and mortality associated with such treatment are not established. METHODS: The records of all patients with thalassemia who received bone marrow transplants from HLA-identical donors in Pesaro, Italy, were examined from October 1982 through May 1992. Detailed evaluation of the outcome was conducted in the 89 patients identified as being in class 1 according to the Pesaro classification, in which hepatomegaly, portal fibrosis, and the inadequacy of iron chelation therapy are considered independent risk factors, and the patients are classified as being in class 1 if none of these factors are present, class 2 if one or two of the factors are present, and class 3 if all three factors are present. Sixty-four of the patients had been prepared for transplantation with a drug regimen in current use that includes busulfan and cyclophosphamide followed by cyclosporine as prophylaxis against acute graft-versus-host disease (protocol 6). RESULTS: There were seven deaths, all within 101 days of transplantation. Two of the 64 patients treated according to protocol 6 died. The probabilities of survival, rejection-free survival, death from causes unrelated to rejection, and rejection were 0.92, 0.85, 0.06, and 0.08, respectively, in the total group and 0.97, 0.93, 0.03, and 0.04 in the 64 patients treated according to protocol 6. Preliminary evidence suggests that there was useful unloading of tissue iron deposits. CONCLUSIONS: The high probability of cure with little early or late morbidity and mortality suggests that patients with class 1 thalassemia who have HLA-identical donors available should be treated by bone marrow transplantation. However, this was not a controlled trial, so we cannot directly compare the outcome with that of conventional treatment. PMID- 8355743 TI - Images in clinical medicine. Tinea Capitis. PMID- 8355744 TI - Prevalence and magnitude of perinatal substance exposures in California. AB - BACKGROUND: Perinatal substance exposure has been linked to many neonatal and obstetrical complications. There have been few population-based epidemiologic studies to identify the prevalence and demographic profiles associated with drugs, alcohol, and smoking during pregnancy. METHODS: We studied a fully probabilistic stratified-cluster sample to estimate the prevalence of perinatal substance exposures in California in 1992. Urine samples from 29,494 women presenting for delivery in 202 hospitals were coded and screened for toxins; the results of toxicology screening were later linked by code number to the subjects' demographic variables and their reported use of tobacco and prescribed drugs. Urinary toxicologic tests provide conservative estimates because they can detect only very recent substance use. RESULTS: The weighted prevalence for perinatal substance exposure was 5.16 percent for the use of one or more drugs, 6.72 percent for alcohol (analyzed independently), and 8.82 percent for self-reported smoking. The percentage of women testing positive for any drug, including alcohol, was 11.35 percent. Estimates for racial and ethnic groups varied widely. Black women had the highest prevalence of total drug use (14.22 percent), alcohol use (11.58 percent), cocaine use (7.79 percent), and tobacco use (20.12 percent). Most drug exposures occurred among white non-Hispanic and Hispanic women. White non-Hispanic women had the second highest prevalence rate for the use of one or more drugs (6.79 percent) and self-reported tobacco use (14.82 percent). Hispanic women had the second highest prevalence rate for alcohol (6.87 percent). CONCLUSIONS: In California in 1992, there were 67,361 estimated perinatal exposures to one or more drugs, including alcohol, and 52,346 self-reported exposures to tobacco. These findings have clinical and public health implications. PMID- 8355745 TI - Nuclear cardiology (2). PMID- 8355746 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 37-1993. A 48-year-old woman with an atrial septal defect and pulmonary hypertension. PMID- 8355747 TI - Should every pregnant woman undergo ultrasonography? PMID- 8355748 TI - Reversal of unawareness of hypoglycemia. PMID- 8355749 TI - Managed competition and the patient-physician relationship. PMID- 8355750 TI - The marketplace in health care reform. PMID- 8355751 TI - The marketplace in health care reform. PMID- 8355752 TI - The marketplace in health care reform. PMID- 8355753 TI - The marketplace in health care reform. PMID- 8355754 TI - Controlling costs through "managed competition". PMID- 8355755 TI - Controlling costs through "managed competition". PMID- 8355756 TI - Controlling costs through "managed competition". PMID- 8355757 TI - Eisenmenger's syndrome in pregnancy. PMID- 8355759 TI - Post-polypectomy surveillance. PMID- 8355758 TI - Post-polypectomy surveillance. PMID- 8355760 TI - Use of anabolic steroids among adolescents. PMID- 8355762 TI - Medical journals and the popular media. PMID- 8355761 TI - Infectious diseases in Somalia. PMID- 8355763 TI - Lidocaine for severe hiccups. PMID- 8355764 TI - Images in clinical medicine. Secondary syphilis. PMID- 8355765 TI - Images in clinical medicine. Left ventricular aneurysm. PMID- 8355766 TI - Images in clinical medicine. Necrobiosis lipoidica diabeticorum. PMID- 8355767 TI - Images in clinical medicine. Streptococcus pneumoniae. PMID- 8355768 TI - Images in clinical medicine. Basal-cell carcinoma. PMID- 8355769 TI - Psychiatric care in further trouble. PMID- 8355770 TI - Clean drugs for Italy? PMID- 8355771 TI - Push for Gulf syndrome research. PMID- 8355772 TI - Brazil's proposed law threatens animal experimentation. PMID- 8355773 TI - Italian health sector in disarray following more scandals. PMID- 8355774 TI - Epidemic misuse. PMID- 8355775 TI - Competition in science. PMID- 8355776 TI - Fetal tissue. PMID- 8355777 TI - Insurance risks. PMID- 8355778 TI - Making more of academic assets. AB - Why is the UK's biotechnology industry still nascent? Academic institutions must exploit the commercial opportunities of the research they support if Britain is to remain internationally competitive. PMID- 8355779 TI - Physiology. And brother begat nephew. PMID- 8355780 TI - Muscular dystrophy. Muscling in on gene therapy. PMID- 8355781 TI - Ancient use of cannabis. PMID- 8355782 TI - Hormonally mediated inheritance of acquired characteristics in Mongolian gerbils. AB - The intrauterine position relative to members of the same or opposite sex that a rodent fetus occupies affects both its morphology and behaviour when adult. Female fetuses that mature between males are androgenized by testosterone crossing fetal membranes, and their phenotypes as adults differ significantly from those of sisters that received less intrauterine exposure to exogenous testosterone. We report here that adult female Mongolian gerbils that gestated between male fetuses produce litters containing a significantly greater proportion of sons than the litters produced by those that gestated between female fetuses. Consequently, daughters delivered by dams that gestated between male fetuses are more likely to have gestated between male fetuses and be androgenized in utero than are daughters of dams that gestated between female fetuses. Female gerbils thus tend to inherit the phenotype (either androgenized or not androgenized) of their respective mothers. PMID- 8355783 TI - Rapid sequence evolution of the mammalian sex-determining gene SRY. AB - In mammals, induction of male sex determination requires the Y-chromosome gene SRY. SRY encodes a protein with a central 'high mobility group' domain (HMG box) of about 78 amino acids. HMG boxes are found in a wide variety of proteins that bind to DNA with high affinity but differing degrees of sequence specificity. The human SRY protein binds to linear DNA with sequence specificity and to cruciform DNA structures without sequence specificity. The DNA-binding activity of the SRY protein resides in the HMG box and mutations in this region are associated with sex reversal in XY females. No function has been ascribed to the portions of the SRY protein outside the HMG box. SRY belongs to a family of genes that are related by sequence homology within the DNA-binding domain: the genes most similar to SRY (> 60%) have been named SOX genes (SRY box genes). None of the known SOX genes is homologous to SRY outside the HMG-box region. Although SRY is an important developmental regulator, its sequence is poorly conserved between species apart from the HMG-box domain. Here we investigate the coding sequence of SRY in primates and find that evolution has been rapid in the regions flanking the conserved domain. The high degree of sequence divergence and the frequency of non-synonymous mutations suggest either that the majority of the coding sequence has no functional significance or that directional selection has occurred. PMID- 8355784 TI - Rapid evolution of the sex determining locus in Old World mice and rats. AB - The Y chromosome-linked sex determining locus (Sry) responsible for testis determination in mammals contains a DNA-binding motif (HMG box) that is conserved across species of marsupial and placental mammals (infraclasses Metatheria and Eutheria, respectively). But little to no sequence similarity is observed in flanking sequences between these two infraclasses, or among orders within each infraclass. We investigated the rate and pattern of evolution for the coding sequence of Sry in Old World mice and rats (subfamily Murinae). We found typical rates of synonymous substitution throughout the gene, but high rates of non synonymous substitution, especially in the C-terminal (non-HMG box) region, when compared to other genes. This region is also characterized by a frame-shift mutation and variation in a trinucleotide repeat motif. These data suggest that the non-box region is either functionally unconstrained or has undergone species specific adaptive divergence. PMID- 8355785 TI - Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit like repeats. AB - Lissencephaly (agyria-pachygyria) is a human brain malformation manifested by a smooth cerebral surface and abnormal neuronal migration. Identification of the gene(s) involved in this disorder would facilitate molecular dissection of normal events in brain development. Type 1 lissencephaly occurs either as an isolated abnormality or in association with dysmorphic facial appearance in patients with Miller-Dieker syndrome. About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller-Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref. 6). These deletions are hemizygous, so haplo-insufficiency for a gene in this interval is implicated. Here we report the cloning of a gene (LIS-1, lissencephaly-1) in 17p13.3 that is deleted in Miller-Dieker patients. Non-overlapping deletions involving either the 5' or 3' end of the gene were found in two patients, identifying LIS-1 as the disease gene. The deduced amino-acid sequence shows significant homology to beta subunits of heterotrimeric G proteins, suggesting that it could possibly be involved in a signal transduction pathway crucial for cerebral development. PMID- 8355786 TI - Spectral motion produces an auditory after-effect. AB - Distortions of perception following prolonged exposure to an unvarying sensory stimulus have been observed since at least the third century BC. The motion after effect is a familiar experience in which, after a few minutes of viewing objects moving in a single direction, a stationary object appears to move in the opposite direction. Similar after-effects have been observed for many visual stimuli, including tilted lines, colours, stereoscopic depth, curvature, spatial frequency, contrast, rotation and motion in depth. In contrast to the rich variety of visual after-effects reported since the 1960s, reports of analogous auditory adaptation effects only appeared in the 1970s, but have continued since then. Some effects of sound source spatial movement perception after adaptation to a spatially moving sound source have been reported. Here we report an auditory perceptual after-effect analogous to the visual motion after-effect, which is caused by adaptation to auditory spectral (frequency) motion. After a few minutes of listening to a simple spectral pattern moving upwards or downwards in frequency space, the same pattern sounds as though it is drifting in the opposite direction when it is stationary. The effect shows binaural transfer, implying that it is generated at the level after binaural interaction. After-effects produced by the motion of spectral peaks are independent of those produced by spectral notches, suggesting separate processing channels for spectral peaks and notches. PMID- 8355787 TI - Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. AB - Brain cholinergic neurons are critical for memory function and their loss may contribute to memory impairment in Alzheimer's disease. One role of cholinergic neurons is to elicit an oscillatory activity called theta rhythm in the hippocampus, a brain region involved in memory processing. Theta rhythm occurs during periods of learning, but its effect on the synaptic plasticity that underlies learning remains unclear. We have studied synaptic plasticity in hippocampal slices during theta-frequency oscillations induced by a cholinergic agonist. Here we report that during these oscillations, synapses are in a state of heightened plasticity and can be modified by what would otherwise be ineffective stimulation. This heightened plasticity is sensitive to the timing of incoming stimuli with respect to the oscillatory activity. The results suggest that cholinergic systems may affect memory formation through the induction of an oscillatory state in which the requirements for synaptic plasticity are dramatically altered. PMID- 8355788 TI - Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity. AB - Duchenne and Becker muscular dystrophy (DMD and BMD) are X-linked recessive diseases caused by defective expression of dystrophin. The mdx mouse, an animal model for DMD, has a mutation that eliminates expression of the 427K muscle and brain isoforms of dystrophin. Although these animals do not display overt muscle weakness or impaired movement, the diaphragm muscle of the mdx mouse is severely affected and shows progressive myofibre degeneration and fibrosis which closely resembles the human disease. Here we explore the feasibility of gene therapy for DMD by examining the potential of a full-length dystrophin transgene to correct dystrophic symptoms in mdx mice. We find that expression of dystrophin in muscles of transgenic mdx mice eliminates the morphological and immunohistological symptoms of muscular dystrophy. In addition, overexpression of dystrophin prevents the development of the abnormal mechanical properties associated with dystrophic muscle without causing deleterious side effects. Our results provide functional evidence for the feasibility of gene therapy for DMD. PMID- 8355789 TI - Helper T-cell development in the absence of CD4-p56lck association. AB - The CD4 and CD8 glycoproteins are expressed on helper and cytoxic T lymphocytes, respectively, and have important functions in the differentiation and activation of these cells. These molecules are thought to participate in signal transduction by binding to the same class II or class I major histocompatibility complex molecules that are engaged by the T-cell antigen receptor. The cytoplasmic domains of both CD4 and CD8 interact with the protein tyrosine kinase p56lck (refs 14-17), an essential participant in thymocyte maturation and T-cell activation. This interaction is required for effective in vitro responses to antigen, suggesting that signalling through p56lck is a major function of CD4 and CD8. Here we investigate the role of the CD4-p56lck interaction during T lymphocyte development by expressing wild-type and truncated products of CD4 transgenes in mice that lack endogenous CD4 and hence have defective helper-cell development. We find that transgenic CD4, which cannot associate with p56lck, can nevertheless rescue the helper-cell lineage when overexpressed. This result indicates that the contribution of CD4 to lineage development need not involve signalling through p56lck, and provides insight into the general function of CD4 and CD8. PMID- 8355790 TI - Coated vesicle assembly in the Golgi requires only coatomer and ARF proteins from the cytosol. AB - Transport vesicles derived from the Golgi apparatus are thought to mediate biosynthetic transport across the Golgi stack. These vesicles are surrounded by a protein coat whose principal constituents are coatomer (a complex of seven distinct subunits or COPs) and ADP-ribosylation factor (ARF, an N-myristylated small GTP-binding protein). The coat proteins of the COP-coated vesicles were originally defined by ultrastructural criteria, however, and it is possible that important but minor coat proteins or cytoplasmic proteins needed for coat assembly may have been overlooked. Here we show that coatomer and ARF are the only cytoplasmic proteins needed for the assembly and budding of COP-coated vesicles. COP-coated buds may therefore form essentially by self-assembly from Golgi cisternae after an initial step in which GTP is used to allow ARF binding. PMID- 8355791 TI - Science research and philanthropy. Government funding dominant. PMID- 8355792 TI - Science research and philanthropy. Charities taking the strain. PMID- 8355793 TI - Science research and philanthropy. A new trend for Japan. PMID- 8355794 TI - Pfizer donates drugs. PMID- 8355795 TI - Gene bill still controversial. PMID- 8355796 TI - MicroGeneSys goes on trial. PMID- 8355797 TI - A strange discipline... PMID- 8355798 TI - Molecular biology. PMID- 8355799 TI - Racial science. PMID- 8355800 TI - A home for the mighty mouse. PMID- 8355801 TI - Neurobiology. Two ears and two eyes. PMID- 8355802 TI - Potassium channels. The response to vagusstoff. PMID- 8355803 TI - Sequence data as evidence. PMID- 8355804 TI - Disparity-sensitive cells in the owl have a characteristic disparity. AB - We experience the visual world as being three-dimensional. A major source of depth information derives from the slightly different views of each eye, leading to small variations in the retinal images ('disparities'). Neurons sensitive to visual disparities are thought to form the neural basis of stereo vision. Barn owls as well as several mammalian species have neurons that are sensitive to visual disparities. But how visual disparities are represented in the brain has been a matter of discussion ever since the first disparity-sensitive neurons were found some 25 years ago. Here we adopt a new approach to this problem and study the neural computation of visual disparities with a paradigm borrowed from auditory research. The measurement of interaural time difference (ITD) has many similarities with the measurement of visual disparity on the formal, algorithmic level. We speculate that the similarities might extend to the level of neural computation. The neural representation of ITD is well understood, and we have studied the representation of disparities with visual stimuli analogous to those successfully used in acoustic experiments. For example, ITD is converted in the brain to a pathlength on an axon that, owing to the finite conduction velocity in neurons, exactly matches the external ITD. This pathlength is called 'characteristic delay'. Our results suggest that there is an analogue of the characteristic delay in stereo vision which we propose to call 'characteristic disparity'. PMID- 8355805 TI - Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel. AB - Parasympathetic nerve stimulation causes slowing of the heart rate by activation of muscarinic receptors and the subsequent opening of muscarinic K+ channels in the sinoatrial node and atrium. This inwardly rectifying K+ channel is coupled directly with G protein. Based on sequence homology with cloned inwardly rectifying K+ channels, ROMK1 (ref. 11) and IRK1 (ref. 12), we have isolated a complementary DNA for a G-protein-coupled inwardly rectifying K+ channel (GIRK1) from rat heart. The GIRK1 channel probably corresponds to the muscarinic K+ channel because (1) its functional properties resemble those of the atrial muscarinic K+ channel and (2) its messenger RNA is much more abundant in the atrium than in the ventricle. In addition, GIRK1 mRNA is expressed not only in the heart but also in the brain. PMID- 8355806 TI - Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. AB - Intracellular Ca2+ signals that last more than a few minutes after the onset of stimulation depend critically on influx of extracellular Ca2+. Such Ca2+ influx can be triggered in many cell types by depletion of intracellular Ca2+ stores without detectable elevations of known messengers. The mechanism by which store depletion can control plasma membrane Ca2+ permeability remains controversial. Here we present evidence for a novel soluble mediator. Calcium depletion of a lymphocyte cell line caused the messenger to be released from intracellular organelles into the cytoplasm and to a much lesser extent into the extracellular medium. The messenger caused Ca2+ influx when applied to macrophages, astrocytoma cells, and fibroblasts and was therefore named CIF (for Ca(2+)-influx factor). CIF appears to have hydroxyls (or hydroxyl and amino groups) on adjacent carbons, a phosphate, and a M(r) under 500. PMID- 8355807 TI - Fission yeast wee1 protein kinase is not required for DNA damage-dependent mitotic arrest. AB - Checkpoints maintain the dependency relationships between discrete events in the cell cycle (for example, ensuring mitosis does not occur before DNA replication is complete). In Schizosaccharomyces pombe, mitotic checkpoints monitor DNA synthesis and the presence of DNA damage. The replication-dependent mitotic checkpoint prevents mitosis by inactivating p34cdc2 kinase. The mechanism by which the DNA damage checkpoint interacts with the mitotic machinery is distinct from that used by the replication checkpoint. The activity of p34cdc2 is controlled, in part, by the wee1 protein kinase, which inactivates cdc2 through phosphorylation at tyrosine-15 (ref. 7). Here we report normal mitotic arrest after DNA damage in S. pombe cells in which the wee1 gene is defective or missing. We suggest why these findings contradict a recent report which suggested that the wee1 gene product was required for DNA damage-dependent mitotic arrest. PMID- 8355808 TI - Development of the cortical dysplasia of type II lissencephaly. AB - A detailed neuropathological study of five immature brains with type II lissencephaly is reported. The cases described include two pairs of siblings. One infant survived for 2 months after birth, the others died at 18, 20, 20 and 32 weeks of gestation. This series of cases demonstrates the sequence in which the malformation develops from mid-gestation to post-natal life and shows that type II lissencephaly is not an intracortical malformation but is the result of massive glial and neuronal ectopia in the leptomeninges. This results from a failure of arrest of neuronal migration due to defects in the integrity of the pial/glial barrier. PMID- 8355809 TI - Axonal neurofilamentous accumulations: a comparison between human and canine giant axonal neuropathy and 2,5-HD neuropathy. AB - The neuropathy produced by the hexacarbon 2,5-hexanedione (2,5-HD) resembles human and canine inherited giant axonal neuropathy (GAN) in the presence of giant axonal swellings that contain accumulations of neurofilaments. The accumulations are both paranodal and internodal in GAN and 2,5-HD induced neuropathy. Detailed morphometry on the neurofilaments reveals that the changes in human and canine GAN are closely similar and differ from those of 2,5-HD neuropathy, suggesting that the mechanisms underlying the formation of the axonal neurofilamentous accumulations differ between the two conditions. In both human and canine GAN, the neurofilaments are more closely spaced and are of greater diameter than in 2,5-HD neuropathy. The changes in the NF in GAN may be the consequence of flattening of the side-arms of the neurofilaments against the axis of the filaments. PMID- 8355810 TI - The neurotoxicity of alpha-chlorohydrin in rats and mice: I. Evolution of the cellular changes. AB - Mice and rats are found to be equally susceptible to developing symmetrical brain stem lesions on exposure to alpha-chlorohydrin and in both species the earliest neurotoxic changes are strictly confined to glial cells, particularly astrocytes; haemorrhages are not found in either species. Minimal evidence of increased vascular leakage of horse-radish peroxidase (HRP) in rats is shown by increased HRP content of perivascular cells within the lesions. Later macrophage invasion and capillary proliferation is accompanied by rare focal leakiness of HRP. Gross astrocytic damage, therefore, does not necessarily impair integrity of the blood brain barrier. While early in intoxication, astrocytes are severely distended with fluid and their organelles seriously disorganized, they do not die but rapidly regenerate their processes. They thus appear to undergo a process of 'clasmatodendrosis' from which they recover. Comparisons are made with the genesis of symmetrical brain stem lesions in other acute energy deprivation syndromes, including Wernicke's encephalopathy. PMID- 8355811 TI - Cerebral amyloid in human prion disease. AB - The clinical and neuropathological features of 21 patients with prion disease were reviewed with special reference to the morphology and immunoreactivity of cerebral amyloid. Six cases had a mutation at codon 102 of the prion protein (PrP) gene and in these the characteristic pathology was the formation of multicentric amyloid plaques which were stained with PrP antibody, whereas spongiform changes were absent in one and minimal in two. In one case, with a 216 base-pair insertion in the PrP gene, there was no spongiform encephalopathy (SE) but cerebellar amyloid was a prominent feature of the pathology. One case with a PrP gene mutation at codon 200 had severe SE but no amyloid. Two iatrogenic and 11 sporadic cases had SE and some form of amyloid was identified in all but three. Amyloid angiopathy and senile neuritic plaques, which stained with antibody to beta-protein, were present in familial as well as in sporadic cases, including some who were rather young to be regarded as having Alzheimer's disease. Cerebellar amyloid and degeneration of granule and Purkinje cells were particularly common findings in sporadic as well as in genetically determined cases. This study serves to emphasize the association between prion disease and amyloid deposition in the brain. PrP is a component of some amyloid plaques in a high proportion of cases with inherited prion disease but may also be found in cases of sporadic SE without known mutations or base-pair insertions in the PrP gene. PMID- 8355812 TI - The cellular pathology associated with Alzheimer beta-amyloid deposits in non demented aged individuals. AB - In this study, we have compared the cellular pathology associated with beta amyloid (beta A) deposits which characterize Alzheimer's disease (AD) in demented patients with pathologically confirmed AD, with that in non-demented aged individuals. Brain sections from two severely demented AD cases, six non-demented individuals with beta A deposits, and six age-matched controls devoid of beta A deposits were double-immunostained with antibodies against beta A, and antibody markers for neurofibrillary tangles (NFT), astrocytes and microglial cells. We found that the severely demented patients displayed numerous plaques of variable morphology, most of which were associated with NFT, hypertrophied astrocytes and reactive microglial cells. In contrast, non-demented patients showed fewer plaques, few or not NFT and less astroglial and microglial reaction. The number of plaques with associated abnormal cellular elements were much lower in non demented than in demented cases. Furthermore, classical plaques were more likely to be associated with abnormal cellular elements than diffuse plaques, which were most often devoid of any associated cellular change. These findings suggest that: (i) beta A plaques in non-demented individuals may represent an early stage of AD; (ii) beta A deposition is the first recognizable pathological abnormality of AD; and (iii) NFT, and astro- and microglial proliferation are later features, possibly secondary to the known dystrophic effects of the beta A peptide and other fragments of its precursor protein. PMID- 8355813 TI - Corpora amylacea could be an indicator of neurodegeneration. AB - We describe an investigation of corpora amylacea (CA) in the brain tissue of Alzheimer's disease (AD) cases and normal ageing controls, using both light (LM) and electron (EM) microscopic techniques. CA populations were shown by routine histological staining of LR White resin sections with methenamine silver and PAS, and were compared with those shown by immunocytochemistry using antibodies to tau, GFAP, tubulin, ubiquitin, beta-amyloid and serum amyloid P component in serial sections. All CA were immunoreactive with anti-tau and all were unreactive with anti-beta-amyloid. Most were immunoreactive with anti-serum amyloid P component, although this was often weak in AD. CA from normal ageing brain were immunoreactive for proteins that are associated with the neuronal cytoskeleton and cell injury. CA from AD brain shared some of these but differed from those in normal ageing brain by being in much larger number and more variable in their immunoreactivity. In all CA, X-ray microanalysis illustrated the presence of the metallic elements Ca, Fe and Cu. Aluminium, often associated with AD, was not present, even in CA from AD brain. Phosphorus and sulphur, probably from phosphorylated proteins associated with degenerating cytoskeleton elements, were usually detected. In AD brain, the greater numbers of CA and their variable biochemical and elemental composition, when compared with CA in the normal ageing brain, suggests that they may derive from a number of sources both neuronal and glial as a result of the neurodegenerative disease. PMID- 8355814 TI - Differential pattern of beta-amyloid protein deposition within cortical sulci and gyri in Alzheimer's disease. AB - We have quantified the pattern of beta-amyloid protein (beta AP) deposition in the sulci and gyri of the frontal cortex in Alzheimer's disease. The distribution pattern in the frontal cortex gyri is unequivocally different from the pattern found in the frontal sulci. These findings, in conjunction with our previous studies, reflect a differential vulnerability between the sulci and the gyri with respect to Alzheimer's disease pathology, sulci being affected to a greater extent. It is probable that the different patterns of deposition relate to the underlying cytoarchitecture of the cortex. PMID- 8355815 TI - Intracranial lipoma of the Sylvian region. AB - The incidental autopsy finding of an intracranial lipoma in the left Sylvian region is reported. This is a rare location for an uncommon lesion. A recent theory on its pathogenesis as a congenital lesion is presented and current methods of diagnosis and treatment are discussed. PMID- 8355816 TI - Eye movements in a familial vestibulocerebellar disorder. AB - Eye movement abnormalities consisting of poor or absent smooth pursuit and vestibulo-ocular reflex suppression, gaze-paretic and rebound nystagmus, slow build-up of optokinetic nystagmus, mildly hyperactive vestibulo-ocular reflex, and a high incidence of strabismus were inherited in an autosomal dominant fashion in 10 members of a non-consanguineous English caucasian family. The onset was in early childhood, but was not congenital. In 7 cases there was no tremor, dizziness, consistent ataxia, or other cerebellar signs that are often associated with these ocular motor deficits, and apart from strabismus, patients were asymptomatic. Magnetic resonance imaging of the propositus was normal. After childhood there appears to be no progression, with the oldest affected member being 40 years. Two members had been prone to falling in childhood, and one admitted to dizziness when tired. This condition, which is probably benign, has not been previously described and may represent a very mild variant of episodic ataxia or a new vestibulocerebellar syndrome. PMID- 8355817 TI - Clinical application of a noninvasive multi-electrode array EMG for the recording of single motor unit activity. AB - Using a recently developed noninvasive EMG recording technique with multi electrode arrays we investigated the pattern and distribution of motor unit action potentials (MUAP) following maximal voluntary contraction of the musculus abductor pollicis brevis. An additional parameter, i.e. muscular conduction velocity (CV) in single motor units, was calculated from the multi-electrode array EMG recordings. From 63 healthy children of various age the normal EMG pattern and CV were derived and compared to the EMG of diagnosed patients known to suffer from Duchenne muscular dystrophy and from spinal muscular atrophy. In normal individuals the muscular CV in neonates was lowest at 1-2 m/s and gradually reached a plateau of 2.9-4 m/s from the age of 4 years onwards. The EMG in 31 children with Duchenne muscular dystrophy showed an abnormal pattern with low amplitude action potentials. In 30 out of 31 patients a significantly lower muscular CV was found. In 10 children with spinal muscular atrophy the EMG showed action potentials of abnormally large amplitude and a reduced recruitment of firing motor units. The muscular CV remained within the normal range. Compared to classical needle EMG the application of this new noninvasive EMG technique in children is painless and offers an easy-to-handle diagnostic tool to differentiate between neuromuscular diseases of denervating or of myopathic origin. PMID- 8355818 TI - Molybdenum-cofactor deficiency: an easily missed cause of neonatal convulsions. AB - Intractable seizures in the neonatal period may be caused by molybdenum-cofactor deficiency, an inborn error which combines the deficiencies of sulphite oxidase and xanthine dehydrogenase. The neurological symptoms of molybdenum cofactor and isolated sulphite oxidase deficiencies are identical. Two new cases are reported, and the literature on neonatal convulsions due to molybdenum-cofactor and sulphite deficiencies is reviewed. Because of the high incidence of neonatal convulsions a search for this deficiency is advocated in each case of unexplained refractory neonatal convulsions. Diagnosis may be missed or delayed on standard metabolic screening for several reasons discussed. By simply using a sulphite strip test in a fresh urine sample an indication for the defect can be obtained. Antenatal diagnosis can be performed by assay of sulphite oxidase activity in a chorionic villus sample. PMID- 8355819 TI - Cortical laminar abnormalities--occurrence and clinical significance. AB - Cortical laminar necrosis is a histopathological entity, related to conditions of cerebral energy depletion. Clinical correlates are supposed to be spastic motor deficits, decreased intellectual capacity and epilepsy. A study was performed in 45 children with cortical laminar abnormalities in signal intensity on MRI. The purpose of the study was to evaluate causes and clinical consequences of these cortical abnormalities on MRI in order to find indirect evidence for the hypothesis that they may represent cortical laminar necrosis. In view of the frequently present concomitant white matter damage, two contrast groups were formed: one group of 40 children with periventricular white matter abnormalities, part of them with subcortical extensions of the white matter damage; and another group of 53 children without abnormalities on MRI. Data concerning history, present clinical condition and final diagnosis were collected. The presence of cortical laminar abnormalities on MRI was found to be strongly associated with a history of cerebral energy depletion, especially hypoxia-ischemia, either in the perinatal period or later in life. Whereas white matter abnormalities tended to be more frequent in premature children, cortical laminar abnormalities tended to occur more frequently in term neonates and older children. The presence of cortical laminar abnormalities on MRI was correlated with an increased risk of spasticity in children without concomitant white matter abnormalities. In children with white matter lesions, cortical laminar abnormalities did not contribute to the risk of spasticity, which was already highly increased by the presence of white matter damage. No association was found between cortical abnormalities on MRI and epilepsy or psychomotor retardation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355820 TI - Visual functions in relation with neonatal cerebral ultrasound, neurology and cognitive development in very-low-birthweight children. AB - In order to determine the relationship between visual functions and neonatal cerebral ultrasound, neurological examinations and cognitive development, a prospective longitudinal study was conducted in 69 high-risk very-low-birthweight children. Visual development was studied at 1 and 2.6 years of corrected age by assessment of visual acuity, binocular visual fields, optokinetic nystagmus and strabismus. Visual impairments were found in 33% at age 1 and in 28% at age 2.6. Visual impairments were related to intraparenchymal damage, as detected by neonatal cerebral ultrasound, as well as to abnormal neurological examinations and lower mean developmental indices. A stepwise multiple regression analysis with neonatal cerebral ultrasound as the dependent variable and visual functions at ages 1 and 2.6 and neurological examinations at ages 1 and 2 as independent variables, however, demonstrated that standardized neurological examinations were better markers of neonatal cerebral damage than visual functions. In cognitive development at ages 1 and 2, the neurological examination at age 1 was the most important variable. In cognitive development at age 3.6, visual functions at age 2.6 were more important. Early visual impairments might thus influence later cognitive development. The effectiveness of appropriate early intervention strategies to stimulate visual and cognitive development in infants with less severe visual impairments should be subject to further study. PMID- 8355821 TI - New subform of the late infantile form of neuronal ceroid lipofuscinosis. AB - Clinicopathological studies of a series of nine children with a new subform of Jansky-Bielschowsky disease or late infantile neuronal ceroid lipofuscinosis (LINCL) is presented. The onset of this subform is between 2.5-3.5 years of age with initial neurological symptoms of abnormal motor skills caused by cerebellar and extrapyramidal signs. Soon after dementia, myoclonic seizures are followed. Visual impairment is more clearly seen after the age of 5 or 6 years. The ultrastructural studies of the skin and/or buffy coat showed abundant lysosomal storage of curvilinear profiles, rarely intermixed with fingerprint profiles. The MRI of the head performed in seven cases, showed initially enlargement of the ventricles that is secondary to basal ganglia atrophy and presence of cerebellar and cerebral atrophy. In 4 of 7 cases (Cases 1, 5, 6, 8) abnormalities in the deep white matter showing increased signals of T2-weighted imaging in the periventricular areas of the fronto-parietal region, internal capsule, tracks of the brainstem, and white matter of cerebellum were seen. These abnormalities were also observed by post-mortem neuropathological studies in three cases (nos. 7-9). The MRI in Cases 7 and 9 was not performed. The electrophysiological abnormalities (EEG, ERG, VER) are similar as described in the classical LINCL. Neuropathological studies done in 3 of 9 cases showed generalized brain atrophy and unique type of neuronal cytoplasmic inclusion body in the basal ganglia, brainstem, dentate nuclei, and rarely, cerebral cortex. These large, round neuronal cytoplasmic inclusions were pink in hematoxylin (HE), violet in cresyl violet, and dark blue with Kluver-Barrera method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355822 TI - Chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies in a new case. AB - Clinical and biochemical findings in a patient affected by chronic GM1 gangliosidosis, presenting as progressive dystonia and mental deterioration, are reported. The patient, a 13-year-old male, showed, at the age of 3 years, an impairment of gait with frequent falls, dysarthria and stuttering. At the age of 6, writing dystonia appeared and subsequently mental deterioration and dystonic postures of arms and legs became evident. The clinical features presented by this patient are similar to those shown by the cases of adult/chronic GM1 gangliosidosis previously reported, except for the early onset. This observation emphasizes the occurrence of dystonia as prominent symptom in chronic GM1 gangliosidosis, underlining that this disease must be considered in the diagnostic approach to the progressive dystonias of the early infancy. PMID- 8355823 TI - Parasomnia with rhythmic movements manifesting as nocturnal tongue biting. AB - The case of a healthy 2-year-old girl with repeated nocturnal tongue biting as a result of rhythmic movements of the jaw associated with body rocking in non-REM sleep is described. Parasomnias manifesting with rhythmic, stereotyped movements of the head, trunk and extremities are well described in healthy children. The term rhythmic movement disorders (RMD) was introduced for these repetive movements in sleep which may appear as head banging (jactatio capitis), body rocking or leg rolling. Severe injuries including fractures, subdural effusions and eye injures are reported. Repeated tongue injuries have not been described as a consequence of RMD. The differential diagnosis from nocturnal seizures is crucial to avoid overtreatment of this benign albeit dramatically presenting condition. PMID- 8355824 TI - Cerebral hemodynamics in subarachnoid hemorrhage evaluated by transcranial Doppler sonography. Part 1. Reliability of flow velocities in clinical management. AB - During recent years, the management of subarachnoid hemorrhage (SAH) has changed, resulting in an increase in early operations and routine administration of nimodipine. Both influenced the indication for transcranial Doppler sonography (TCD). Furthermore, investigations detected discrepancies between Doppler findings and neurological status. In a prospective study, the reliability of TCD was investigated in patients with SAH treated with intravenously administered nimodipine. Patients with large hematomas were excluded. Neurological deficits immediately after surgery or within the first 48 hours were classified as not delayed, and therefore not necessarily due to vasospasm. The most remarkable points of this study are that there is no significant difference between the flow velocities for Hunt and Hess Grades I and II when compared with those for Grade III, and that Grades IV and V seem to be affiliated with the lowest velocities. When the flow velocities of 11 patients who developed delayed ischemic deficits (DIDs) were compared with those of patients with no deficit, no significant difference was seen. A significant increase in velocity in the days before the onset of DID was found only in 3 of 11 cases. Eight patients showed either constant high or constant low velocities or even, in some cases, decreasing time courses. High flow velocities did not necessarily mean impending neurological deficits: 8 of 66 patients tolerated flow velocities over 200 cm/s. Therefore, it no longer seems to be justified to proclaim that TCD is able to predict neurological deficits, although it is doubtless able to detect vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355826 TI - Cerebrovascular histopathology after intracarotid infusion of Gelfoam in the rat. AB - To evaluate the histopathology of Gelfoam on the cerebral vasculature, 42 Sprague Dawley rats weighing 250 to 300 g received internal carotid artery infusions of 0.3 ml of Gelfoam solution (5 mg/ml) or normal saline (0.9%). The animals were killed at 1 hour, 5 hours, 3 days, 1 week, 2 weeks, and 4 weeks after the infusion. The brains were removed, sectioned, and stained with hematoxylin and eosin. Examination of brain sections revealed Gelfoam emboli lodged primarily in the small leptomeningeal arteries. At 5 hours after infusion, inflammatory cells were noted in the arterial walls with vessel occlusion. Further canalization of vessels was noted at 1 week. At 4 weeks, Gelfoam was not seen in the specimens. This study suggests that Gelfoam acts as an embolic agent in vessels over short periods of time with no residual inflammatory activity postinfusion. PMID- 8355825 TI - Cerebral hemodynamics in subarachnoid hemorrhage evaluated by transcranial Doppler sonography. Part 2. Pulsatility indices: normal reference values and characteristics in subarachnoid hemorrhage. AB - In previous publications on the diagnostic value of transcranial Doppler sonography (TCD), conflicting results concerning predictive capacities for evaluating vasospasm by measuring flow velocities were reported, and the necessity to examine pulsatility indices (PIs) was stressed. PIs are known to give useful information on cerebral hemodynamics in cases of stenosis of the extracranial internal carotid artery and cerebral arteriovenous malformations. Whether the examination of PIs can give additional information in cases of subarachnoid hemorrhage (SAH) and allow prediction of impending delayed ischemic deficits (DIDs) is still unclear. Normal reference values for the Gosling pulsatility index, the Pourcelot resistance index, and the first Fourier pulsatility index were established in a series of 97 normal subjects. A significant increase in the indices was found as age increased, and there was a strong relation between the indices. There were no statistically significant differences between the right and left sides. An inverse relation was found between the flow velocity and PIs in the middle cerebral artery. In a prospective study of 455 follow-up TCD examinations in 66 SAH patients treated routinely with nimodipine, three different groups were analyzed separately: Group I, patients without DIDs; Group II, patients with DIDs; and Group III, patients with neurological deficits not strictly classifiable as DIDs. The analysis of all three groups together showed a typical time course after the onset of SAH: initially elevated PIs normalized around the tenth day after bleeding. According to Fisher grading, the amount of subarachnoid blood influences the increase in PIs significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355827 TI - Giant aneurysms of the proximal anterior cerebral artery: report of three cases. AB - Aneurysms of any size involving the A1 segment of the anterior cerebral artery are unusual, but giant aneurysms in this location are exceedingly rare, with only five cases previously reported in the literature. We report three cases of A1 segment giant aneurysms presenting with mass effect that were successfully treated. A discussion of the salient features of diagnosis and treatment are presented, along with a brief review of the literature describing these aneurysms. The role of newer imaging modalities, including magnetic resonance imaging, magnetic resonance angiography, and intraoperative angiography, is discussed. The three patients were treated by direct exploration, trapping, and endaneurysmal decompression. Giant A1 segment aneurysms present a unique opportunity to safely trap and decompress the aneurysm with definitive cure. PMID- 8355828 TI - Spinal arterial aneurysm: case report. AB - Isolated aneurysms of the spinal artery (not associated with arteriovenous malformations) are exceptionally rare. Fewer than 17 cases have been reported in the literature. We report a case of an isolated spinal artery aneurysm causing acute subarachnoid hemorrhage. Spinal artery aneurysms are contrasted with the more common intracranial aneurysms in terms of presentation and pathogenesis. The various clinical presentations of spinal artery aneurysms are discussed as well. A summary of all reported cases of spinal aneurysms, with and without associated arteriovenous malformations, is listed. PMID- 8355829 TI - Pachymeningoencephalitis: case report. AB - Hypertrophic cranial pachymeningitis is uncommon. We report the first case of pachymeningitis extending to the cerebral parenchyma (pachymeningoencephalitis) and involving the bone and extracranial soft tissue. The clinical features and pathogenesis are discussed. PMID- 8355830 TI - Neuro-ophthalmic complications of intracranial catheters. AB - We report four patients who sustained direct injury to the brain after insertion of intraventricular shunts and pressure monitoring lines, which resulted in permanent neuro-ophthalmic deficits. These included hemianopsia from an optic tract lesion, esotropia and residual bilateral facial paresis from dorsal pontine injury, unilateral blindness from damage to the optic nerve, and dorsal midbrain syndrome from catheter compression in the region of the posterior commissure. Although presumably rare, such injuries should be considered in diagnosing patients with neuro-ophthalmic complaints after insertion of such devices. PMID- 8355831 TI - Successful radiosurgical treatment of a dural arteriovenous malformation: case report. AB - An anterior fossa dural arteriovenous malformation was treated with radiosurgery. The lesion was irradiated with 3000 cGy to the 80% isodose line of an 18-mm collimator. Angiography revealed complete thrombosis 3 years after treatment. The case is described in detail, and the pertinent literature is reviewed. PMID- 8355832 TI - Isolated metastatic melanoma of the cerebellopontine angle: case report. AB - Malignant melanoma is a common cause of central nervous system metastases. This report describes an extremely rare case of metastatic melanoma presenting as an isolated cerebellopontine angle tumor. Clinically and radiographically, the lesion mimicked an acoustic neuroma. The patient had neuro-otological symptoms, including tinnitus, vertigo, sensorineural hearing loss, facial nerve dysfunction, and prominent cerebellar dysfunction. Magnetic resonance images showed a lesion of the internal auditory canal and cerebellopontine angle that was hypointense on T1-weighted images, hyperintense on T2-weighted images, and enhanced after the administration of gadolinium. T2-weighted images showed significant cerebellar edema. Subtotal resection of the tumor through a suboccipital craniotomy palliated the symptoms, but the patient died of tumor progression 6 months later. In contrast to other metastatic tumors of the temporal bone, melanoma initially metastasizes to the internal auditory canal and is characterized by early neurovascular infiltration. This report highlights the pathophysiological characteristics, radiological findings, differential diagnosis, and treatment of metastatic melanoma of the internal auditory canal and cerebellopontine angle. PMID- 8355833 TI - Simultaneous presentation of symptomatic subependymomas in siblings: case reports and review. AB - Two young adult siblings independently developed similar neurological complaints that included headaches, photophobia, nausea, and intermittent lancinating facial pains. Magnetic resonance imaging revealed fourth ventricular lesions that required surgery in both patients. A pathological review revealed subependymomas with virtually identical histological features. The clinical features and common pathological findings of both patients suggest that familial subependymomas may have a maldevelopmental origin with genetic implications. PMID- 8355834 TI - Percutaneous catheterization of the jugular bulb with a Doppler probe: technical note. AB - On-line measurement of jugular venous bulb oxygen saturation may be of clinical value in patients with head injuries. Cannulation of the jugular bulb may be technically difficult in this group of patients. Trendelenberg positioning and head rotation may be associated with increased morbidity or mortality. A technique is described whereby catheterization can be performed with the head of the bed elevated and the neck in a neutral position. A needle with a Doppler probe is used to distinguish between the carotid artery and the internal jugular vein. The needle and the probe are then directed to the audible signal representative of the jugular vein. Once the vein is penetrated, placement of a fiberoptic oxygen saturation catheter is performed in the usual fashion. This technique allows auditory feedback to guide the course of the needle and decreases the morbidity that may be associated with the "blind" technique. PMID- 8355835 TI - A micrometric multiple electrode array for the exploration of gasserian and retrogasserian trigeminal fibers: preliminary report. Technical note. AB - The determination of the target for percutaneous thermocoagulation of the trigeminal rootlets has been generally based on the analysis of subjective clinical verbal and motor responses as assessed by freehand displacement of an electrode active at its straight or curved distal tip. In a previous report, we demonstrated that sensory and motor trigeminal evoked potentials are of practical value when attempting to localize the position of trigeminal electrodes. This report describes the technical features of a multiple electrode array designed to provide simultaneous access to various segments along a chosen trigeminal division or divisions, correlating at each segment clinical and electrophysiological data with radiological landmarks in the individual patient. The system consists of an outer needle with four windows at a distance of 15 mm from the tip. A multiple electrode array occludes the windows with four isolated caps for stimulation and recording. After correlating clinical verbal and motor responses with sensory and motor evoked potentials at each window and inter se, a target window is selected. A thermocouple fitted with a micromanipulator allows the accurate placement of the center of the active tip at the center of the chosen window. Preliminary data from 25 patients indicate that the technique provides a reliable sequential analysis of clinical, electrophysiological, and radiological data along the explored tract. PMID- 8355836 TI - Thompson-Farley spinal retraction system. PMID- 8355837 TI - Thompson-Farley spinal retraction system. PMID- 8355838 TI - Synthes spine drill instrumentation. PMID- 8355839 TI - Biomagnetic technologies: magnetic source imaging (MSI). Magnes Biomagnetometer. PMID- 8355840 TI - A temporal transsylvian approach to anterior circulation aneurysms. PMID- 8355841 TI - Pull-out strength of Caspar cervical screws. PMID- 8355842 TI - Management of unruptured intracranial arteriovenous malformations: a decision analysis. PMID- 8355843 TI - The influence of halothane, enflurane, and isoflurane on motor evoked potentials. PMID- 8355844 TI - Glucose consumption in recurrent gliomas. AB - In order to investigate the clinical significance of glucose consumption (GC) in recurrent gliomas, positron emission tomography with 18F-labeled fluorodeoxyglucose was measured in 18 cases of histologically verified recurrent gliomas. The GC of the tumors were categorized into four groups. Five tumors were in Group IV, the highest GC, four were in Group III, eight were in Group II, and one was in Group I. Masses in Groups III and IV were clearly defined as a hot spot higher than or similar to the GC of the contralateral cortex. Half of the recurrent gliomas showed the lower GC of Group I or II, but two thirds of these were histologically high-grade gliomas. Although GC in the recurrent gliomas did not always increase as expected, a focal increase of GC, even mild and small, in the area of previous surgery is diagnostically important. Tumors with high GC showed high histological malignancy, irrespective of tissue damage. Patients with tumors of low GC had longer survival rates than those with high GC, although statistical significance was not obtained. Thus, positron emission tomography with 18F-labeled fluorodeoxyglucose was useful for detecting the recurrence of gliomas and suggesting their histological malignancy and prognosis. Care should be taken because viable tumor cells could be present in areas of low GC and small recurrent masses could be missed because of the poor spatial resolution of positron emission tomography. PMID- 8355845 TI - Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury. AB - The present study was conducted to further our understanding of the relationship between performance on neuropsychological tests and functional status after head injury and to provide information on the relative usefulness of neuropsychological tests as outcome measures in clinical trials of brain injury. We sought to select the fewest number of 19 neuropsychological tests administered to 110 patients that, in combination, were most closely related to outcome (as measured by the Glasgow Outcome Scale (GOS) and to the remaining neuropsychological measures. The relationship of memory and intellectual deficits to functional status was also considered. To address these questions, we analyzed 19 neuropsychological measures and GOS scores of 110 severely brain injured patients from the Traumatic Coma Data Bank. Of 19 neuropsychological measures compared with GOS at 3 and 6 months, four tests (Controlled Oral Word Association, Grooved Pegboard, Trailmaking Part B, and Rey-Osterrieth Complex Figure Delayed Recall) provided the closest relationship to GOS and to the remaining 15 tests. Similar analyses were performed on 30 moderately injured patients to test the generality of our findings across different levels of patient severity. The same four tests were found to be highly predictive of GOS. Grooved Pegboard, a test of fine motor coordination, accounted for 80% of the variation in GOS. Fifteen percent of 116 patients with severe brain injury could not complete a neuropsychological battery and 39% were excluded because of previous brain injury or known substance abuse. PMID- 8355847 TI - Subtemporal amygdalohippocampectomy for treating medically intractable temporal lobe epilepsy. AB - A SUBTEMPORAL AMYGDALOHIPPOCAMPECTOMY technique has been developed for mesial temporal lobe epilepsy. The conventional subtemporal approach has been modified to diminish temporal lobe retraction and the risk of damage to the temporal lobe. In the new technique, the surgeons' position has moved from above to below and the approach has been changed from anterolateral to posterolateral, thereby avoiding the voluminous and steeply inclined anterior temporal lobe. By this modified approach, it was unnecessary to remove the roof of the external auditory meatus and it was estimated that both the retraction pressure and the extent of temporal lobe retraction were reduced. To date, surgeons using this approach have operated on four patients with temporal lobe epilepsy whose epileptic foci were in the mesial temporal structure; the inferior temporal gyrus, the temporal tip, the vein of Labbe, and the ventral bridging veins were preserved. After surgery, two patients became completely free of seizures and the other two showed over 90% reduction in seizure frequency without neurological sequelae. Postoperative visual field examination revealed full visual fields without quadrantanopsia. This approach can preserve the temporal stem and lateral temporal lobe, it can be used to remove as much of the posterior hippocampus as necessary, and it can be extended to conventional lobectomy if it is indicated. PMID- 8355846 TI - Sigmoid diverticular perforation in neurosurgical patients receiving high-dose corticosteroids. AB - Perforation of colonic diverticula is a complication of corticosteroid use that has not been described in the neurosurgical literature. Between 1987 and 1992, 719 patients who underwent surgery for primary and metastatic brain and spinal tumors of the central nervous system received 2246 to 4936 mg of methylprednisolone given over at least 7 days. Five patients in this group (all men, ages 50-69 yr) experienced a sigmoid diverticular perforation at a mean dose of 3947 mg of methylprednisolone (range, 2240-6160 mg). Of these five, two had a known history of diverticular disease. In contrast, during this same period, 3749 patients who underwent neurosurgical procedures for non-neoplastic conditions did not receive corticosteroids and experienced no colonic perforations. All five patients with colonic perforations presented with abdominal pain and had free intraperitoneal air that was revealed on radiographs of the abdomen. Perforation of a sigmoid diverticulum was confirmed in all five at exploratory laparotomy. Four patients had good outcomes, and one died. We conclude the following: 1) patients over age 50 who receive high-dose corticosteroids are at risk for sigmoid colonic perforation, and these medications should be used with caution in such patients; 2) if possible, lower total doses of perioperative corticosteroids should be used in patients with known diverticular disease; and 3) because corticosteroids mask many of the inflammatory signs of perforation, this diagnosis should be considered in any patient with abdominal discomfort, fever of unknown origin, or unexplained leukocytosis. PMID- 8355848 TI - Thoracic disc disease: experience with the transpedicular approach in twenty consecutive patients. AB - TWENTY CONSECUTIVE PATIENTS were treated for symptomatic thoracic disc herniation with the transpedicular approach. Most patients had severe, incapacitating local or radicular pain. Myelopathy was uncommon as magnetic resonance imaging allowed an early diagnosis. Computed tomography, after myelography, provided further information necessary for surgical planning. Three patients had disc disease at two levels. Nine central and 14 lateral disc herniations were found. Disc calcification or an associated osteophyte was identified in six instances. Although the size of the disc herniation correlated with the amount of cord compression, no radiological features were found to be correlated with neurological function. The transpedicular approach was used in all patients. New curettes, specifically designed for the procedure, allowed the removal of all discs, including central and calcified fragments. A modified arthroscope was used to confirm neural decompression in some instances. One year after surgery, all 20 patients were significantly improved and 8 patients were asymptomatic. Apart from the duration of the symptoms, no other factors were found to affect outcome. The findings suggest that the prognosis of thoracic disc herniation is excellent if the disease is recognized early. The transpedicular approach, using curettes specifically designed for the procedure, can be an effective and safe method of surgical decompression in carefully selected patients. PMID- 8355849 TI - Chronic subdural hematoma: the role for craniotomy reevaluated. AB - The management of chronic subdural hematoma in the adult patient is approached with a variety of different surgical techniques. The trend in recent years has been toward treatment with burr holes or twist-drill holes rather than craniotomy. The rationale for this has been based on the assumption that burr holes and twist-drill holes offer equivalent efficacy and lower morbidity and mortality. This viewpoint is not, however, universally accepted, and many surgeons feel that craniotomy is superior to a burr hole for the management of this condition. In a review of 92 patients presenting over a 3-year period with 112 chronic subdural hematomas, 49 underwent craniotomy and 43 underwent burr hole treatment. The recurrence of hematomas, requiring another operation, occurred in 8.6%; operative mortality was 2.2% at hospital discharge and 4.4% at follow-up. No patient died as a consequence of the operative procedure. There was no significant difference in the incidence of postoperative complications, hematoma recurrence, or operative mortality among the different surgical groups. Previous reports concerning the superiority of burr holes over craniotomy are not substantiated by this review. Although the issue concerning optimal therapy has not been resolved by this review, at this time, craniotomy remains a valid and safe technique for the management of patients with chronic subdural hematoma. PMID- 8355850 TI - A risk/benefit analysis of spinal manipulation therapy for relief of lumbar or cervical pain. AB - Approximately 12 million Americans undergo spinal manipulation therapy (SMT) every year. Renewed interest in this method requires an analysis of its reported risks and possible benefits. This review describes two patients with spinal cord injuries associated with SMT and establishes the risk/benefit ratios for patients with lumbar or cervical pain. The first case is a man who underwent SMT for recurrent sciatica 4 years after chemonucleolysis. During therapy, he developed bilateral sciatica with urinary hesitancy. After self-referral, myelography demonstrated a total block; he underwent urgent discectomy with an excellent result 3 months after surgery. The second patient with an indwelling Broviac catheter and a history of lumbar osteomyelitis underwent SMT for neck pain. Therapy continued for 3 weeks despite the development of severe quadriparesis. After self-referral, he underwent an urgent anterior cervical decompression and removal of necrotic bone and an epidural abscess with partial neurological recovery. An analysis of these cases and 138 cases reported in the literature demonstrates six risk factors associated with complications of SMT. These include misdiagnosis, failure to recognize the onset or progression of neurological signs or symptoms, improper technique, SMT performed in the presence of a coagulation disorder or herniated nucleus pulposus, and manipulation of the cervical spine. Clinical trials of SMT have been summarized in several recent articles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355851 TI - The surgical anatomy of the perforating branches of the basilar artery. AB - The perforating branches of the basilar artery were examined in 14 brain stems injected with india ink or methylmethacrylate. Three groups of the perforators were distinguished: the caudal, the middle, and the rostral. The caudal perforators varied in number from two to five and in diameter from 80 to 600 microns. In addition to their terminal branches, which entered the foramen cecum, the perforators occasionally branched off the pontomedullary artery, the pyramidal vessels, and the hypoglossal branches. The middle perforators arose either separately from the basilar artery or along with the basilar artery collateral branches. They ranged in number from five to nine and in diameter from 210 to 940 microns. The perforators gave rise to the pontomedullary artery (8.3%), the long pontine arteries (25.0%), and the anterolateral vessels (100%). The rostral perforators originated from the terminal part of the basilar artery (91.6%), as well as from the superior cerebellar artery (91.6%) and the posterolateral artery (16.6%). They varied in number from one to five and in diameter from 190 to 800 microns. The anastomoses among various perforating vessels were noted in 41.6 to 66.6% of the cases. The authors discussed the possible clinical significance of the anatomical data observed in this study. PMID- 8355852 TI - The frequency of intradural conjoined lumbosacral dorsal nerve roots found during selective dorsal rhizotomy. AB - The frequency of occurrence of conjoined nerve roots (CR) in the cauda equina has been reported to range from 0.3% to 2%. We found intradural conjoined nerve roots in 13 of 123 (10.6%) patients undergoing selective dorsal rhizotomy for spasticity due to cerebral palsy. The anomaly occurred most commonly at L5-S1 and S1-S2. There was no consistent relationship to other anomalies of segmental anatomy. Our finding of a significantly higher number of conjoined nerve roots in these patients is primarily due to the surgical exposure of the entire cauda equina. This anomaly is more common than previous reports have indicated. PMID- 8355853 TI - Neurofibromatosis 2 in the pediatric age group. AB - Bilateral acoustic neurofibromatosis or neurofibromatosis 2 (NF2) is an autosomal dominant disease predisposing to the formation of multiple tumors in the central and peripheral nervous system. Vestibular schwannomas (VSs) are considered to be the hallmark of the disease, but other tumors and ocular findings occur as well. In patients that do not carry the NF2 mutation, VSs usually occur in the fifth or sixth decade of life. VSs in patients with NF2 are often bilateral and become symptomatic in the third or fourth decade of life. In order to define the early manifestations of NF2, we examined nine children who either had one parent with NF2 or had multiple skin or spinal tumors suggestive of NF2. In addition to neurological, dermatological, and ocular examinations, all patients were studied by gadolinium-enhanced magnetic resonance imaging of the brain and spine. None of the children exhibited symptoms or signs due to VSs. However, VSs were detected during the neuroradiological work-up in six children. Seven children developed symptoms or signs due to skin or spinal tumors. Slit lamp examination detected cataracts in four patients as young as 10 years of age. The diagnosis of NF2 in the pediatric age group requires a high degree of suspicion and should be considered in children with multiple central nervous system or skin tumors without cafe-au-lait spots or Lisch nodules. Because VSs are unlikely to produce the signs seen at the time of admission, careful examination of the skin and eyes is necessary and should be followed by gadolinium-enhanced magnetic resonance imaging of the brain and spine. First-degree relatives need to be examined as well. PMID- 8355854 TI - Ruptured suprasellar dermoid cyst presenting olfactory delusion (Eigengeruchs erlebnis). AB - A 24-year-old man sought treatment of a long-standing olfactory delusion (Eigengeruchs erlebnis) and associated psychotic symptoms, which disappeared after the removal of a suprasellar dermoid cyst. The pathophysiology of the phenomenon is discussed. PMID- 8355855 TI - [The natural history of peripheral arteriopathy]. AB - An the content of atherosclerosis, knowledge of the natural history of peripheral arteriopathy of the lower limbs is of fundamental importance. The authors review the literature involved; in particular they examine the prevalence of peripheral arteriopathy, its incidence and multimodal course in time. It is very interesting to state the cardiovascular morbility and mortality owing to pathology of the coronary district as well as the cerebral one during the course of peripheral arteriopathy. The literature conclusions are not univocal; this matter is principally due to different approach methodologies. As far as arteriopathy of inferior limbs is concerned, the literature shows that we can have a worsening in the local picture for 25% of the cases involved, considering the worst hypothesis; amputation involves at the most 5% of the cases. The real problem in these patients is the presence of arteriosclerotic disease involving other different vascular districts. PMID- 8355856 TI - [Biochemical-physical and rheologic changes in the blood of patients with angina pectoris]. AB - Viscosity, erythrocyte flexibility, haematocrit value and fibrinogen concentration have been studied in fifty patients: twenty-five of them suffering from angina pectoris and the other twenty-five in good health. The parameters considered in the first group have been found out to be much higher in comparison with the control group. In particular, when the values of blood viscosity are corrected for the standard haematocrit as to 45 per cent, the significance of the values themselves between the two groups of patients is cancelled. In such a way the dependence of viscosity on haematocrit is demonstrated. The results obtained are discussed in relation to the literature data which are not always univocal. PMID- 8355857 TI - [ST elevation during ergometric test: correlation with coronary angiography]. AB - BACKGROUND: ST elevation during ergometric stress test (EST) is relatively rare. Its prevalence depends upon the tested population but occurs more frequently in patients who have had myocardial infarction or variant angina. This phenomenon is very rare in patients with typical exertional angina and its pathogenesis is still unclear. MATERIAL AND METHODS: We studied a group of 75 consecutive patients with exertional angina who underwent EST and coronary angiography. A symptom limited EST was performed in the upright position on a cycloergometer with load increases of 25 watts every 3 minutes and 12 leads were monitored during all test. Coronary angiography was performed according to Judkins technique. From these patients, according to Froelicher's criteria, a group of 49 patients (age 32-68, mean 51.6 years), without myocardial infarction and/or left ventricular asynergy, was selected. RESULTS: All patients had a coronary artery disease (16 patients with 3 vessels, 11 patients with 2 vessels and 22 patients with 1 vessel disease). The EST was positive for ST depression in 31 patients (63.3%) and for ST elevation in 5 patients (10.1%), while 13 patients (26.6%) had a non diagnostic EST. The ST elevation occurs in V1-V2 and it was associated in all cases with a stenosis in the left anterior descending (LAD) artery. Therefore we divided the 19 patients with LAD stenosis into two subgroups: subgroups A (9 patients, mean age 49.6 years) with LAD stenosis > or = 90% and subgroups B with LAD stenosis between 70% and 90%. ST elevation occurs in 5 patients (55.5%) of subgroup A and in no patient of the subgroup B. Moreover, in the subgroup A ST elevation seems to be related to the anatomic localization of the stenosis: in fact it appears in 83.3% of patients with LAD stenosis located before the onset of the first diagonal branch. CONCLUSIONS: From these data it can be desumed that ST elevation in V1-V2 that occurs in patients with exertional angina and without myocardial infarction or variant angina is strongly predictive of a very important LAD stenosis. PMID- 8355858 TI - [Safety of the dipyramidole echocardiography test in elderly coronary disease patients]. AB - We prospectively studied the feasibility and safety of high-dose dipyridamole echocardiography in 166 patients (77 younger and 89 elderly patients) referred for clinical evaluation of coronary artery disease. The feasibility of dipyridamole echocardiography test was 80.5% in the young and 82% in the elderly (p = n.s.). The incidence of side effects during dipyridamole echocardiography was similar in two groups, except for dyspnea which was observed in 20% in the older and 4% in the younger (p < 0.01). Our data demonstrate that the dypiridamole test combined with echocardiographic monitoring of regional myocardial contractility may be considered a valid non invasive method for evaluating coronary artery disease in the elderly. PMID- 8355860 TI - [Effect of cilazapril therapy on diastolic filling and left ventricular hypertrophy in patients with arterial hypertension]. AB - BACKGROUND: Of the main aspects of hypertension, left ventricular hypertrophy and appearance of cardiac dysfunction seem to be the most common and to produce an early and severe cardiac deterioration. Even in the presence of normal systolic function diastolic filling abnormalities are described. The efficacy of many antihypertensive drugs to decrease blood pressure and to reduce left ventricular hypertrophy has already been demonstrated. Cilazapril is a new ACE-inhibitor that in previous studies showed a very important antihypertensive effect. To assess its capacity, in long-term treatment, to reduce left ventricular hypertrophy we performed a prospective study on patients with mild hypertension. MATERIAL AND METHODS: Nineteen patients (aged 48 +/- 15 years) with mild hypertension (mean arterial pressure automatically recorded for 24 hours with blood pressure ambulatorial monitoring) were treated with cilazapril (5 mg/day) for 1 year. Doppler echocardiography was performed: at the beginning, after 6 months and after one year of therapy. The following parameters were evaluated: interventricular septal and posterior wall thickness, LV end-diastolic diameter, LV mass index, early (E) and late (A) diastolic filling flow velocities and the ratio E/A. RESULTS: A significant decrease was observed in mean arterial pressure (from 130 +/- 14 mmHg at beginning to 102 +/- 11 mmHg at six months of therapy and to 103 +/- 9 mmHg at one year of therapy). A significant reduction in LV hypertrophy and an improved diastolic filling pattern of the left ventricle was shown after six months of therapy with cilazapril; this improvement still remained after 1 year of therapy. CONCLUSIONS: In this study antihypertensive efficacy of cilazapril has been confirmed. Moreover, in long treatment, cilazapril has been useful to reduce left ventricular hypertrophy and to improve diastolic filling without significant side effects. PMID- 8355859 TI - [Treatment of ischemic heart disease in the elderly. Comparison of diltiazem, verapamil and gallopamil]. AB - The medical therapy of myocardial ischemia in elderly patients has not been well evaluated. We studied the age-related changes in 127 patients with proved coronary artery disease and stable effort angina the efficacy and the safety of diltiazem 120 mg tid, verapamil 120 mg tid and gallopamil 50 mg tid a medium term parallel, double blind cross-over placebo controlled study. All patients have been clinically and ergometrically evaluated. In middle-age patients diltiazem, verapamil and gallopamil induced a significant increasing of exercise duration and time to onset ST segment depression > or = 1 mm. In the elderly patients both verapamil and diltiazem as increased the exercise duration and ischemic threshold, while the diltiazem did not increased the exercise duration even if the time of onset ST segment depression > or = 1 mm is increased. At peak exercise the ST segment depression have been reduced both in middle-age and elderly patients after active drugs. Weekly angina and DNT consumption have been significantly reduced after diltiazem, verapamil and gallopamil in middle-age and elderly patients. Side effects have not been relevant even if gallopamil as a lower frequency of them in comparison to diltiazem and verapamil. No patients stopped the treatment because major side effects. Our experience suggests that diltiazem, verapamil and gallopamil have a similar efficacy and rare well tolerated. The choice of one instead of another must be suggested on the basis of side effects developing. PMID- 8355861 TI - [Increase in capillary permeability induced by endotoxin: protection with antioxidants and glutathione]. AB - Endotoxin administration increases capillary permeability in experimental animals and this is one of the most relevant events in the pathophysiology of endotoxin shock; the aim of the present experiment was to demonstrate that the action of endotoxin on capillary permeability is due to oxygen-free radicals generation. Experiments were performed on the mesocecum of male Wistar rats; fluorescent labeled bovine albumin (FITC-BSA) was injected intra-arterially to evaluate the capillary permeability; the mesocecum microcirculation was observed by fluorescent light. Permeability was quantified by changes in the number of leaky sites at 10 minute intervals for an hour. The effects of Endotoxin (DIFCO 0111:B4, 30 mg/kg i.a.) were assessed in rats receiving 1) saline, 2) reduced glutathione (250 or 500 mg/kg i.p.), 3) three different nitrones (PBN, DMPO, POBN) (6.25 mg/kg i.p.) whose action is to "trap" oxygen radicals. Capillary permeability largely increased in a few minutes in control rats but it was quite unaffected in rats receiving glutathione or nitrones. As a conclusion the increased capillary permeability observed after endotoxin injection in rats may be due to an oxygen-radicals generation. PMID- 8355862 TI - [Charcoal and isoflurane alveolar washout in low-flow circuit]. AB - The inclusion of charcoal filters in anaesthetic low-flow systems contributes to the acceleration of the kinetics of isoflurane (Forane). In twenty subjects, scheduled for extra- and intracranial surgery, ventilated with a low-flow system (Ohmeda Excel OAV7750 with rebreathing cassette) with a mean total flow of 0.7 l/min, awakening was complete within 5 minutes from stopping isoflurane and including charcoal in the circuit. At the awakening, the expiratory concentration of isoflurane was 0.23% (95% confidence intervals: 0.19-0.27%): these values are similar to those of MACawake of isoflurane after fast alveolar washout. The use of charcoal during low-flow anaesthesia makes low-flow systems more flexible in their use; the anaesthetic level is more easily controllable and accidental overdosing of volatile anaesthetics can be immediately removed. PMID- 8355863 TI - [Subarachnoid anesthesia with Sprotte 24-G needle in ambulatory surgery]. AB - In order to evaluate the possibility of using a selective subarachnoid anesthesia in ambulatory surgery we studied its feasibility with a Sprotte needle 24 G in 103 patients (range 15-67 years) undergoing a knee joint arthroscopy. The subarachnoid anesthesia was achieved with Sprotte needle 24 G with introducer with patient on lateral decubitus. Hyperbaric bupivacaine 1% (0.05 mg/cm height) was used in order to obtain a selective homolateral metameric anesthesia between L1 and S3. The numbers of attempts were 1.29 (range 1-4). We involved the homolateral determatomeres in 94% of our attempts, adding a weak anesthetic action on contralateral ones. In the remaining 6% of the patients the anesthesia was bilateral and extending in an overlying manner. Anesthesia was adequate for the time needed to perform all the surgical procedures. Nevertheless in 3 patients the tourniquet was painful. We registered systemic hypotension only in 2% of the patients (a reduced systolic pressure value > 30%). No cases of postdural puncture headache were registered. Non postural atypical headache was seem in 3.9% of the patients. Urinary retention necessitating catheterization was noted only in 3 cases. A weak backache was revealed in 8.8%. When interviewed after surgery, 98% of our patients fulfilled the technique. In spite of technical difficulties that the use of the Sprotte needle may present, the selective subarachnoid anesthesia may be a safe alternative to the other anesthetic procedures for ambulatory surgery of the legs. PMID- 8355864 TI - [Effects of clonidine vs trinitroglycerin on myocardial oxygen balance and on pulmonary gas exchange after myocardial revascularization]. AB - The authors examined the effects of clonidine, a preferential alpha-adrenergic agonist, upon myocardial oxygen balance and pulmonary function during the perioperative period in patients undergoing CABG surgery. Anesthesia was provided by fentanyl infusion reaching the final dose of 100 micrograms.kg.min-1 in 10 minutes before skin incision. Ten patients received clonidine 0.125 mg intravenously after induction of anesthesia; a group of 10 patients was managed identically except for nitroglycerin infusion during the pre-CPB period, in order to keep the aortic pressure in the normal range. Intergroup differences in hemodynamics, respiratory data, rewarming time, post-operative ST-tract pattern and enzyme values were evaluated. Results are suggestive (in the clonidine group) for ameliorating myocardial oxygen balance by reducing oxygen consumption indexes (systolic aortic pressure, cardiac index, rate pressure product) and increasing coronary blood flow [coronary perfusion pressure (p < 0.01)] at the end of the surgery and intensive care. Global oxygen consumption reduction, recorded in the clonidine group patients, the oxygen available being unchanged, ameliorated the total oxygen balance mainly after sternotomy (p < 0.05) and at the end of bypass (p < 0.05). Cardiac index was greater during the awakening and rewarming period in intensive care and the ventilatory/perfusion ratio was improved, allowing a minor minute ventilation required in clonidine group patients, specially during admission to intensive care. PMID- 8355865 TI - [Gabexate mesilate (FOY), a new synthetic protease inhibitor, in the treatment of shock. An Italian multicenter study]. AB - BACKGROUND: Circulatory shock has been accepted as a consequence of a chain of biochemical events beginning with production of proteases and ending with an uncontrolled generation of oxygen radicals. OBJECTIVE: To evaluate the efficacy of gabexate-mesilate (FOY) in circulatory shock in man. Gabexate-mesilate is a new wide-range synthetic protease inhibitor that also has antioxidant properties. DESIGN: Clinical multicenter study with open design that has been compared with some Japanese controlled studies performed using identical parameters and very similar protocols. EXPERIMENTS: 59 shocked patients were treated with FOY in 9 italian intensive therapy units. Circulatory shock was traumatic (n = 14), traumatic-hemorrhagic (n = 25), septic (n = 11) or of mixed type (n = 9). Evaluation of seriousness of shock on beginning of therapy and during the follow up period was performed on the basis of the same "shock score" (Ogawa and Fujita, Jap J Surg 12:122, 1982) that was used in Japanese clinical studies on FOY in shock. 1.45 mg/kg/hour of FOY were injected i.v. during 48 hours. Conventional therapy was permitted but steroids and aprotinin were excluded. The follow-up period was 9 days. RESULTS: 8 patients died. The mean initial score of the survivors was 8.2; after 8 hours it was 5.0 and after 12 it was 4.0. No adverse reactions were reported. The above quoted survival was greater than that of Japanese studies although the initial score was quite the same. However these studies were controlled and demonstrated gabexate-mesilate to be significantly more active in shock therapy than placebo. They also demonstrated an activity of FOY greater than that of aprotinin when shock was associated to acute respiratory insufficiency and to coagulopathies. CONCLUSIONS: Gabexate mesilate might be useful in therapy of circulatory shock due to its wide-range inhibition of proteases and to its antioxidant properties. PMID- 8355866 TI - [Diazepam and dehydrobenzperidol: comparison of 3 protocols of oral premedication in children]. AB - Oral diazepam, oral droperidol and oral diazepam plus droperidol were compared as premedicants in 75 children weighting from 10 to 20 kg. The sedation and anti salivary action were more satisfactory with droperidol alone and with droperidol plus diazepam. PMID- 8355867 TI - [The Mallampati's scale: a study of reliability in clinical practice]. AB - The need to predict the rank of difficulty of tracheal intubation is of paramount importance in anaesthesia as has been well documented in numerous studies. We assessed the use of the Mallampati scale as possible predictive indicator of difficult tracheal intubation in a study conducted on 700 patients. The rank of difficulty determined during the pre-anaesthesiological examination by the Mallampati scale, was compared to the Cormack scale as assessed by the laryngeal direct examination at the beginning of anaesthesia. The correlation between the two first ranks of both scales was highly significant. The evaluation by the scale of Mallampati showed a good sensibility and a low specificity with incorrect overestimation only for the difficult intubation. In our study orotracheal intubation was rated difficult in 10.4% of the patients by the Mallampati scale and in 11% of the patients score by the Cormack scale. The chin to jugulum distance, also studied as a possible predictive parameter, did not correlate with the Cormack scale. PMID- 8355868 TI - [Quality of care at a regional emergency medical system]. AB - The Emergency Medical System (EMS) in the district of Florence is based upon the activity of 13 Emergency Mobile Unit (EMU). The activity of such a huge system is difficult to evaluate: we have concentrated our attention upon the diagnostic process assuming that "correct diagnosis = correct treatment = benefit for the patient". Then we compared diagnoses set on EMU to diagnoses made in hospitals, giving to each comparison a score from 1 to 5. In terms of quality the services of the EMS in Florence seem to be effective, since in 72% of cases the Hospital Emergency Department has confirmed the diagnoses achieved under emergency conditions, and in 12% only there has been remarkable difference. Comparing the diagnoses made on EMU to that at the hospital discharge, in two thirds of cases there is excellent correlation. PMID- 8355869 TI - [General anesthesia for endobronchial laser therapy in a heart and lung transplant recipient]. AB - The introduction of heart, lung and heart-and-lung transplants, only recently performed in Italy, has presented the anesthetist with the problem of the anesthesiological treatment of newly transplanted patients whose number will increase over time. For some time our unit has used general anesthesia using spontaneous breathing for endotracheal and endobronchial laser therapy. This solution was adopted in the case of a patient who had undergone a heart-lung transplant using an "a domino" technique some 90 days earlier. The authors discuss the results of the anesthesiological technique used taking into account the particular hemodynamic and respiratory characteristics of these patients. PMID- 8355870 TI - [Treatment of pheochromocytoma in children. Experience with 3 clinical cases]. AB - The authors report their own experience in three cases of paediatric phaeochromocytoma. Before surgery the patients received alpha-adrenergic blocking drugs; two of them also received calcium channels blocking drugs and in one of them was employed a beta-adrenergic blocking drug too. Before surgery the patients received blood and plasma expandera infusions for two weeks. Hypertension during surgery was treated with phentolamine infusion. The employment of an invasive haemodynamic monitoring was very important. The authors believe that such management, already employed in adult patients, is the best choice in paediatric patients too. PMID- 8355871 TI - [Cholecystectomy by video celioscopy in the elderly. An obligatory choice?]. AB - The videocelioscopic technique is becoming increasingly widely used in the treatment of cholelithiasis. In view of the results obtained, the authors underline the advantages of this method in geriatrics. PMID- 8355872 TI - [Tumors of the breast in old age]. AB - After reviewing the literature on this topic the authors studied all patients admitted to the Institute of Surgical Pathology I at the University of Pavia for breast cancer between 1-1-1974. An analysis of the findings revealed that: (a) Out of 993 patients with breast cancer, 204 (20.54%) belonged to the geriatric age group (> 65 years old) and of the latter 135 (66.17%) belonged to the 3rd age group and 69 (33.82%) belonged to the 4th age group (> 75 years old). (b) In the 3rd age group 25 (18.51%) were benign tumours and 110 (81.48%) were malignant, whereas in the 4th age group 4 (5.79%) were benign and 65 (94.20%) were malignant. (c) Familial patterns were also examined and were found to be positive in 47 (23.03%) cases in the 3rd age group and in 30 (14.71%) in the 4th age group. (d) In the physiological anamnesis it is interesting to note that there was 1 menarche before 12 (0.9%) in the 3rd age group; delayed menopause (after 50) in 66 cases (60%) in the 3 rd age group and in 29 cases (44.61%) in the 4 th age group. (e) In the pathological anamnesis of the patients in question it was observed that the most frequent site of previous tumours was the breast (72 cases, equivalent to 10.9% in the 3rd age group; 9 cases, 13.8% in the 4th age group). (f) In the next pathological anamnesis and at EOL it was observed that the tumours was most often found in the supero-external quadrant, in the right breast in the 3rd age group (66 cases, 48.89%) and in the left one in the 4th age group (42 cases, 60.87%). (g) Test included breast cancer scan, mammography, aspirated needle and biopsy where required. (h) Surgery in the form of Halsted's mastectomy was the preferred therapy and as early as possible. Some Authors use conservative therapy. (i) Histological tests were performed in all patients and revealed that the most frequent malignant tumour was ductal carcinoma. (j) Postoperative complications took the form of wound suppuration. (k) Only one tumour (carcinoma) was observed in male patient aged 83 years old, without metastasis. From the above findings it can be concluded that the most evident risk factor for breast cancer is the influence of the estrogen hormone. PMID- 8355873 TI - [Immediate reconstruction after radical mastectomy for breast carcinoma with a Becker-type expander prosthesis]. AB - In recent years, the breast has won importance from the female psychology point of view. After ablative surgery for cancer, the loss of the breast gives rise in the woman to a feeling of refusal of her new body shape. Reconstruction produces positive feelings in the patient. The best-used surgical technique for operable breast cancer is modified radical mastectomy. An immediate reconstruction of the missing breast is considered when the following conditions are fulfilled: desire for reconstruction, age of the patient, clinical and pathologic evaluation (tumor size-tumor grade-lymph-node status). After modified radical mastectomy with "en bloc" removal of axillary lymph nodes, an immediate reconstruction is performed by lining the surfaces with human fibrin glue (Tissucol) followed by the insertion of a prosthesis of appropriate size (Becker Expander Mammary Prosthesis Type 1) in the subserratus-subpectoral position. Human fibrin lining reduces the incidence of capsular contracture and effusion production. A suction drain is placed in the axillary area and is removed after 5 days. The use of expanding type prostheses means that the patient must return for further expanding. When the pathologic features are negative, the delayed nipple areola reconstruction is possible with the full-thickness skin grafts in the groin or in pre-existent appendectomy incision. By this procedure, adjuvant chemotherapy or radiation therapy can be performed if required. From 1987 to 1991 the procedure has been performed in 35 cases of mammary neoplasm (mean age 40 years) at INRCA Department of Surgery of Ancona). No evidence of adverse effect on the natural course of the breast disease for have been seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355874 TI - [The role of node-picking lymphadenectomy in the treatment of differentiated carcinoma of the thyroid]. AB - A retrospective analysis of the treatment of spreading of differentiated thyroid carcinoma to regional lymph nodes was performed in 201 patients observed in 1973 1991. In 183 patients with no clinical metastatic involvement (A group), no lymph node excision was performed. In 36 patients with limited metastatic lymph node involvement (B group), a node-picking lymphadenectomy was performed. After 1977, all patients were treated also with metabolic radiotherapy postoperatively. Actuarial 15-year survival was 98.28% in A group and 87.50% in B group (n.s. difference). In 15 patients with lymph nodal relapse, actuarial 10-year survival was 83.4%. The survival figures are not different from those obtained after more radical operations. So, in limited metastatic involvement of neck lymph nodes by differentiated thyroid carcinoma, in the opinion of the Authors, node-picking lymphadenectomy is equally effective as more radical surgical procedures. PMID- 8355875 TI - [The surgical treatment of renovascular hypertension in subjects with a single kidney]. AB - Renovascular hypertension in subjects with a solitary kidney, though an infrequent condition, requires surgical direct revascularization procedures either to reduce the hypertensive state and, more important, to preserve renal function. This paper reports a series of six surgically treated cases between 1982 and 1990, with at least two years follow-up. Preoperative renal function, as evaluated by BUN and blood creatinine, was reduced in 5 cases, the remaining one being normal. All subjects were hypertensive at admission: in four cases drug therapy was ineffective for restoring normal pressure values. All subjects had previously undergone surgical nephrectomy: in 3 cases for shrunk kidney, in 2 for failure of a previous attempt of renal revascularization, and one for renal tuberculosis. 3 subjects were concomitantly affected with abdominal aortic aneurysm, and one had previously undergone aortobifemoral bypass. Treatment of the concomitant aortic lesion and renal artery revascularization were carried out at the same operation. Operations performed were TEA of residual renal artery in 3 cases, prosthetic reconstruction in 2 and intraoperative transluminal angioplasty by Gruentzig balloon catheter in one. Over a two-year follow-up renal function remained good in 4 cases, while one subject required a second surgical revascularization due to late acute thrombosis of a previous aortorenal saphenous vein graft. Acute early postoperative renal failure occurred in one case and permanent haemodialysis was instituted. No deaths were recorded in this series. PMID- 8355876 TI - [Traumatic lesions of the colon]. AB - Four patients operated on at the Clinica Chirurgica II of IRCCS--Policlinico San Matteo of Pavia for trauma involving the colon were reviewed. All were males and their ages ranged from 14 to 84 years (mean 43.5 years). Injuries of the colon were found on 9 per cent of all patients operated on for abdominal penetrating injuries and on 6 per cent of patients with blunt injuries. The authors recall the pathogenetic mechanisms, clinical patterns, some grading systems proposed for quantifying the severity of the lesion. Our experience has shown that in blunt trauma the prognosis is worse because there were many associated organ injuries. These condition the early mortality for shock and exsanguination. PMID- 8355877 TI - [Burn patients in major emergencies. The preparation of air-drop kits for emergency surgical-resuscitation use]. AB - The kit described is for air-dropping for immediate use in the surgical treatment and resuscitation of burn victims in major emergencies when there is no direct access to the disaster area by rescue teams or vehicles. The kit can also be used to make up for deficiencies in medicines or medical materials in remote hospitals that have admitted people with severe burns who are not immediately transferable to other hospitals. PMID- 8355878 TI - [Necrotizing enterocolitis]. AB - Necrotizing enterocolitis (NEC) is an important cause of neonatal morbidity and mortality. During the last few years, there was an increase in the incidence of this disease, associated with a better knowledge of NEC, and an increase in survival rate, associated with the development, even from a technological point of view, of neonatal intensive care units. In this study, the authors first perform the diagnostic procedures and describe the anatomical and clinical characteristics of NEC, then evaluate by standard criteria a series of patients observed during the last 5 years, revising the various surgical treatments adopted and the results obtained. PMID- 8355879 TI - [A proposal for a computerized clinical records file for a department of general surgery]. AB - The author suggest a computerized program for filing clinical records of surgical institution. The proposed file is written in DB III plus (Ashton-Tate) and consists of one file .dbf and 4 files .prg. The database file contains anagraphic and clinical data of the patients. The program files make it possible to attribute a personal code to patients, print records of single patients, calculate the time of operation and assist in codifying diagnostic related groups (DRGs). The author stresses the utility of a medical computerized records system containing only few but important clinical data. It makes it possible to perform the most analysis of surgical series without the aid of a professional programmer. PMID- 8355880 TI - [Injuries due to seat belts. Comments on a clinical case]. AB - The authors report a case of associated injuries (thoracoabdominal trauma with multiple rib and sternum fractures, perforation of the small intestine, abdominal cutaneous ecchymosis) caused by a seat belt, and describe the possible seat-belt mechanisms of lesion in road accidents. Some clinical aspects are discussed; in particular the diagnostic problems concerning a seat-belt syndrome as well as the limits of effectiveness in the use of belts. PMID- 8355881 TI - [Umbilical flowmetry: effect of measurement sites on the results]. AB - Pulsed Doppler duplex sonography was performed longitudinally on 11 uncomplicated singleton pregnancies from 20 to 41 week's gestation (87 measurements). Blood flow velocities were recorded at 3 locations: abdominal insertion site (O), in the free floating part (C), placental insertion site (PL). The objective of the study was to determine whether the C site S/D ratio, the quickest and easiest to perform, relates to the other sites. The S/D ratio measurements fell from the near abdomen (O) to the free floating part (C) to the placental insertion site (PL) between 25-35 week's gestation. Statistical analysis, including analysis of variance for repeated measures and student t test, showed no significant difference in S/D ratio among the locations before 25 and after 35 week's gestation. The S/D ratio at the O site was significantly higher than at the PL site between 25-35 week's gestation; the C site was not significantly different from the PL site. PMID- 8355882 TI - [The role of laparoscopy in the evaluation of chronic pelvic pain]. AB - Chronic pelvic pain, defined as cyclic or acyclic pain reported for a minimum of six months, is one of the most common gynecological symptoms and one of the most important in terms of social costs. From January 1987 to December 1991, 127 patients suffering from chronic pelvic pain were submitted to diagnostic laparoscopy at the Department of Obstetrics and Gynecology of the Universita Cattolica del Sacro Cuore in Rome. The mean age of the patients was 30 years, ranging from 14 to 46. All patients were submitted to bimanual pelvic examination upon hospital admission, and most of them (No. = 99, 78%) to pelvic ultrasonographic examination. In 117 patients (92%) samples for the isolation of Chlamydia trachomatis in 5-iodo-2-deoxiuridine treated McCoy cell cultures were obtained from the cervix, the endometrium and the cul-de-sac peritoneal fluid. At laparoscopy, in 25 patients (20%) the exam showed normal pelvic anatomy, whereas in 102 patients (80%) some pelvic pathology was found. The most frequent conditions observed were: pelvic adhesions in 55% (No. = 70), endometriosis in 29% of the cases (No. = 37), and other pathologies (non-endometriotic ovarian cysts, hydrosalpinges, myomas, etc.) in 25% of the cases (No. = 32). At the comparison of bimanual examination and laparoscopic findings, out of 71 patients with normal findings at bimanual examination, 75% (No. = 53) were found to have abnormal findings at laparoscopy; out of 55 patients with abnormal bimanual examination, 11% (No. = 6) were found to have normal laparoscopic findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355883 TI - [Echography in the diagnosis of postoperative complication in gynecology]. AB - The authors report their experience regarding the use of ultrasonic instruments to control the postoperative iter of gynecological, oncological or urological surgery. These types of surgery may be complicated by urethral lesions, retroperitoneal or subfascial sero-hematic stasis, lymphocele, urethrohydronephrosis or vescical dysfunctions with urinary stasis which, if identified at an early stage, can be resolved by surgery. Out of 88 cases of gynecological surgery with a high risk of complications which were followed using ultrasound during the postoperative period, complications occurred in 11 cases (12.5%): their early identification also enabled adequate treatment to be performed using an echo-guided aspirated needle technique or using the application of drainage catheters. PMID- 8355884 TI - [Lymphocytic subpopulations in malignant ascites of ovarian origin. Flow cytometric analysis]. AB - A flow-cytometric analysis of ascitic fluid (AF) and peripheral blood lymphocyte subpopulations (LS) was performed on 16 patients with ovarian malignancy (OM) and 5 with metastatic peritoneal carcinomatosis (MPC). AF lymphocytes are 58% of total leukocytes in OM patients, 37% in MPC patients, while blood lymphocytes are 14% and 17%, respectively. AF absolute lymphocyte count (total and individual LS) is higher in OM patients. OM patients AF lymphocytes are: T = 70%, CD4+ = -37%, CD8+ = 32% (CD4/CD8 = 1.39), B = 5%, NK cells = 4-10%, CD25+ = 20%, CD69+ = 15%, CD71+ = 3%. In MPC patients the values are generally similar, though CD4+ cells are +7%, CD8+ cells = -14% (CD4/CD8 = 3.17), CD69+ cells = -8%. Untreated OM patients have a AF total and percent lymphocyte count higher than treated ones. Among the latter, however, the CD4/CD8 ratio as well as the number of CD4+, inducer, CD25+ and CD71+ cells are higher. In terms of percent values, the most striking differences involve total T and B lymphocytes (81-87% vs 56-62%, and 10% vs 2%, respectively). With the only exception of absolute NK cell count, OM patients show no correlation between AF and peripheral blood LS pattern. These results agree only partially with data from the literature. Pathophysiologic and clinical considerations support the practical usefulness of LS analysis in AF from OM patients. PMID- 8355885 TI - [The effect of pregnancy and breast feeding on bone mineral content]. PMID- 8355886 TI - [Fetal choroid plexus cysts: a real dilemma!]. AB - The clinical significance of the fetal choroid plexus cysts, observed by prenatal sonographic examination, is now a days still discussed. A consequence of this situation is the discordance of opinions about the question of whether karyotype analysis is always necessary to evaluate chromosomal anomalies sometimes correlated, especially in the presence of (as some authors have reported) large (> 1 cm), bilateral, persistent cysts and of other structural abnormalities. We have effected a prospective study to estimate the incidence of fetal choroid plexus cysts and to establish the obstetrical behaviour to be adapted in these cases. During 834 routine ultrasonographic examinations at 18-21 weeks' gestational age, we have evaluated the presence of fetal choroid plexus cysts in 9 fetuses, with an incidence of 1.07%. Three of these cysts were larger than 1 cm, three were bilateral. Karyotype analysis, effected in all cases, diagnosed a case of Trisomy 18 in a fetus who ultrasonographically showed, in addition to a unilateral cyst of 1.2 cm, also a diaphragmatic hernia. Careful ultrasound follow up revealed that all the cysts disappeared spontaneously, but two of them (whose dimensions were larger than 1 cm) were still visible at 24 weeks' gestation and probably this age will be too advanced to begin a chromosome analysis. In conclusion, we think that the presence of fetal choroid plexus cysts always imposes a careful ultrasonographic evaluation of fetal morphology and, since there is always the risk that other small fetal anomalies (evocative of abnormal fetal karyotypes) wight not be noted, we believe that it is better, in any case, to recommend to the patient a prenatal cytogenetical analysis. PMID- 8355887 TI - [Cholestasis in pregnancy]. AB - The authors report the main morphological and functional alterations of the liver during the course of pregnancy. The size of the organ does not change and there is a slight (20%) reduction of hepatic flow. Hepatic function is partially modified in view of the following factors: reduced protein synthesis (in particular the albumin component), increased serum levels of cholesterol and triglycerides mediated by steroid hormones, inhibition of canalicular secretion and consequent diminution of the liver's excretory function, variations in serum levels of many markers of cholestasis so much so that they become unreliable due to pregnancy. The high level of sexual steroids also influences cholecystic kinetics: progesterone, in particular, negatively affects the contractile response to cholecystokinin-pancreozymin stimulus. The paper then reports some historical data including those which led to the definition of "gravidic cholestasis" as a clinical condition. The incidence of the disease varies considerably in relation to the geographical area and genetic factors. In Sweden and Finland the percentage ranges between 1 and 3%, whereas much higher values (12-22%) are reported in Chile and among the American Indians. The latest data for Italy reveal an incidence of 0.34%. The onset of disease is conditioned by familial predisposition due to an enhanced sensitivity to estrogens or excessive production of estrogenic metabolites. Among the hepatocytic changes induced by estrogens are the reduced fluidity of sinusoidal plasmatic membranes and the inhibition of vasolateral Na+K+ ATPase pump activity. The last months of gestation are characterized by a "cholestatic state" which may vary in severity from slight symptoms, to itching and idiopathic jaundice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8355888 TI - [The effect of two contraceptive methods (EP vs. IUD) in relation to inflammatory changes and CIN]. AB - The authors examine Smear Test phlogistic picture repair processes, endometrial cells and preneoplastic lesions in women who used IUD and EP. The research has pointed out that infection due to Actinomyces is only (present) in IUD carriers. CIN affects for 4.2% of IUD carriers. PMID- 8355889 TI - [Endometriosis of the abdominal wall after cesarean section]. AB - The finding of endometriosis of the abdominal wall is a rare event; we describe three cases observed after cesarean section. The first case is an endometriosis of the rectus abdominis, first occurrence in literature. The second case describes a localization limited to the subcutaneous tissue. The third case describes the involvement of the entire abdominal wall. Only two patients complained about excruciating abdominal pain during menstrual bleeding. In one case pain was only an occasional event. PMID- 8355890 TI - Home infusion therapy: comparison of costs for intravenous immunoglobulin. AB - Increasing utilization of intravenous immunoglobulin home therapy has stimulated a scramble by various home health agencies for this high-priced business. A comparison of costs illustrates wide disparity among companies serving patients in New Jersey. PMID- 8355891 TI - Management of upper extremity ischemia. AB - Upper extremity ischemia is insidious in onset and debilitating. It accounts for 1 to 4 percent of all peripheral vascular procedures. Once the site of the symptomatic lesion is determined, an extrathoracic extra-anatomic bypass often can provide long-lasting relief. PMID- 8355892 TI - Adenosquamous carcinoma of the pancreas. AB - Adenosquamous carcinoma of the pancreas is an unusual tumor. The authors review the case report of a 70-year-old male. Radiologic and computer tomography (CT) findings for adenosquamous carcinoma were indistinguishable from adenocarcinoma of the pancreas. PMID- 8355893 TI - Radiographic assessment of traumatic rupture of the thoracic aorta. AB - The authors discuss the advantages and limitations of radiographic modalities in assessing traumatic rupture of the thoracic aorta (TRTA). TRTA is one of the most frequent causes of death from high-speed deceleration accidents and other blunt trauma sustained during motor vehicle accidents. PMID- 8355894 TI - The Evers case: 1984 decision has lasting impact. AB - In 1984, the Supreme Court of New Jersey established the standard for determining physician liability for the delay in the diagnosis of cancer. The effects and implications of that 1984 decision are lasting. The case involved a failure to diagnose breast cancer. PMID- 8355895 TI - Ventricular dysfunction and pulmonary function in OSA syndrome. AB - Patients with obstructive sleep apnea (OSA) have increased cardiovascular morbidity and death as a result of myocardial ischemia and both pulmonary and systemic hypertension. Early detection allows for proper risk stratification and treatment. PMID- 8355896 TI - Peripheral alpha-agonists provide another option for hypertension. PMID- 8355897 TI - ANA concerned with prescription denial by out-of-state pharmacies. PMID- 8355898 TI - The clinical challenge of progressive myoclonus epilepsy. AB - Health care providers who care for patients with seizure disorders should be able to recognize progressive myoclonus epilepsy. Progressive myoclonus epilepsy is a syndrome confused with myoclonic seizures and other epilepsies. The main symptom is myoclonus, a brief involuntary muscle jerk of varying intensity that can throw a patient against a wall or to the ground. This article describes major types of progressive myoclonus epilepsy, a typical case presentation and two clinical drug trials available for these patients. The focus of clinical drug trials is to identify a drug that controls the myoclonus and improves the quality of life for the affected individual. There is no cure for patients with progressive myoclonus epilepsy. 5-hydroxy-L-tryptophan and piracetam are two drugs available through clinical-research protocols to patients with progressive myoclonus epilepsy. PMID- 8355899 TI - Urban, low-income, African-American and Hispanic youths' negative experiences with condoms. Implications for nursing intervention. AB - Research suggests that the rate of HIV infection is increasing dramatically in African-American and Hispanic youths who live in low-income, urban areas. Nurses need information about these youths' negative experiences with condoms to intervene effectively in the spread of acquired immune deficiency syndrome. This article discusses negative experiences with using condoms that were reported by a subsample of condom users (n = 975) from a household probability sample of low income, urban, African-American and Hispanic youths. Condom users were asked about 12 different negative experiences with condoms. Results from this household survey highlight a need for nurses to provide clients with specific directions about how to use condoms correctly and to encourage clients to practice putting on condoms. PMID- 8355900 TI - Nurse-managed clinics provide access and improved health care. AB - With the closing of hospitals, communities must work together to provide access to health care. This article reports on the development of a prenatal nurse managed clinic, and its expansion to include a birth center, well-child/sick child clinic, teen-pregnancy program and family planning clinic. The staff includes four certified nurse midwives, five pediatric nurse practitioners, a bilingual certified clinical nurse specialist and a bilingual social worker. Through the innovative management of these professionals, the incidences of low birth-weight infants and pregnancy-induced hypertension have decreased. Since 1988 when the clinic first opened, first trimester enrollment has increased from 12 percent to 25 percent and third trimester enrollment has decreased from 44 percent to 21 percent because clients go to the clinic earlier. At the largest emergency room in the county, visits by Medicaid recipients under six years of age have decreased 27 percent from the time the pediatric clinic opened. PMID- 8355902 TI - Women in dentistry. PMID- 8355901 TI - Simvastatin, pravastatin and lovastatin: three options for lowering cholesterol. PMID- 8355903 TI - Dentists' opinions of the effect of changes in Accident Compensation Corporation regulations on dental practice and patient access to dental services. AB - A 50 percent random sample of practising dentists in New Zealand was invited to complete a questionnaire aimed at determining their opinions on the effects of changes to Accident Compensation Corporation regulations on dental practice and patient access to treatment. Seventy-six percent of those surveyed returned the survey form. The results suggested that the introduction of a fee schedule for dental treatment in 1989 restricted practitioners' treatment decisions, and prevented some patients from receiving what was considered to be ideal care, largely on the basis of cost. Although the scheduled fee did not always cover the cost of treatment, many practitioners absorbed this shortfall. However, since the 15 percent cut in fees payed by ACC, which was introduced in 1992, practitioners are now finding it necessary to charge the patient for the amount not covered by ACC. Dentists state that this is further restricting the kind of treatment they can provide, and that patients can afford. Some patients are now unable to have any treatment for dental injuries resulting from accidents as they cannot afford it. Some practitioners feel that the introduction of a fee schedule and the requirement of a patient contribution to treatment costs have had some positive effects, but the majority feel that significant barriers to treatment have been created by the ACC changes. PMID- 8355904 TI - A combined orthodontic and orthognathic surgery approach to the treatment of extreme deep overbite in an adult. AB - This report describes a combined orthodontic and orthognathic surgery approach to the treatment of extreme deep overbite in an adult male. An aesthetically pleasing and stable result was achieved without extensive restorative or prosthetic treatment and their inevitable sequelae. The functioning occlusion exhibited bilateral canine rise and an absence of non-working side interferences on lateral excursion. Incisal guidance with disclusion of posterior occlusal surfaces occurred on protrusive function. PMID- 8355905 TI - The small faces of Romania--a report on a dental tour to Romania in August 1992. PMID- 8355906 TI - Occlusion and restorative dentistry: Part II. AB - When planning treatment for major reconstruction of a dentition, occlusal factors which can affect the comfortable functioning of the masticatory system are a prime consideration. Anterior guidance and posterior support contribute significantly to the comfortable functioning of the masticatory system. Aesthetic factors are also significant for, in providing anterior guidance, the alignment, lengths, and proportions of incisors are as critical as their shape, colour and surface texture. Finally, treatment does not end with the insertion of the fixed and removable prostheses. Continual maintenance over the years can be as challenging as the reconstruction. PMID- 8355907 TI - Restoration of primary anterior teeth with composite crowns. AB - For children with extensive caries of primary teeth, or with deformed or traumatised teeth, restoration with composite using a crown form gives excellent results. Strength is gained by full crown coverage. The aesthetics are very acceptable. The technique also allows primary teeth to be modified to resemble permanent teeth when these are missing and the primary teeth are being kept until more definitive treatment is provided. Caries is usually well controlled, and space loss due to further tooth breakdown is avoided. PMID- 8355908 TI - Dental caries in 5-year-olds. PMID- 8355909 TI - Penile radionuclide studies in impotence: an overview. PMID- 8355910 TI - Evaluation of 99Tcm-teboroxime scintigraphy for the differentiation of reversible from fixed defects: comparison with 201T1 redistribution and reinjection imaging. AB - The aim of this study was to compare 99Tcm-teboroxime and 201T1 myocardial studies with particular regard to the classification of perfusion defects as reversible or fixed. Twenty patients with a history of previous myocardial infarction and suspected effort ischaemia underwent exercise 201T1 scintigraphy with early (4 h) redistribution and reinjection scans, exercise and rest 99Tcm teboroxime imaging and coronary angiography. Using a qualitative scoring of static planar images, the perfusion defects were classified as reversible or fixed. 201T1 and 99Tcm-teboroxime gave comparable results in the evaluation of the individual vessels (sensitivity 65%, specificity 80% and 85%, respectively). The stress-redistribution 201T1 sequence classified 45 defects as reversible and 28 as fixed, the stress-rest 99Tcm-teboroxime studies classified 47 as reversible and 26 as fixed (NS). The stress-reinjection 201T1 images, however, characterized 64 defects as reversible and nine as fixed (P < 0.005 versus 201T1 redistribution, P < 0.0005 versus 99Tcm-teboroxime rest). In conclusion, this study shows that rest 99Tcm-teboroxime and 201T1 redistribution give comparable results but that significantly more defects are classified as fixed by 99Tcm teboroxime than by 201T1 if reinjection of the latter tracer is performed. PMID- 8355911 TI - Delayed recovery of myocardial perfusion after successful coronary angioplasty of infarct-related artery in patients with prior myocardial infarction. AB - We studied the status of myocardial perfusion before and after coronary angioplasty (PTCA) of infarct-related artery using stress thallium scan in patients with prior myocardial infarction. Twenty-six patients who had anterior myocardial infarction caused by single-vessel disease at the left anterior descending coronary artery were involved. Patients were classified into the following four groups according to the stress-redistribution thallium scintigraphic findings before PTCA: complete redistribution (two cases), incomplete redistribution (12 cases), partial redistribution (seven cases) and no redistribution (five cases). In the group with complete redistribution, the extent of residual ischaemia in the infarct area decreased significantly after PTCA but infarct size only slightly. In the groups with incomplete and partial redistribution, the extent of residual ischaemia and infarct size decreased significantly after PTCA. In contrast, the group with no redistribution showed a slight decrease in the extent of residual ischaemia and a gradual decrease in infarct size beginning 3 months after PTCA. Clinical findings including electrocardiogram indicated that the patients with incomplete redistribution had more viable myocardium and the patients with no redistribution had more scarring. The groups with incomplete and partial redistribution showed characteristics intermediate between complete and no redistribution. The change of infarct area after PTCA was different between the four groups, but both residual ischaemia and infarct size decreased in all groups. Thus, PTCA of the infarct-related coronary artery is useful even in the patients with prior myocardial infarction, even in patients with no redistribution shown by stress thallium scan. PMID- 8355912 TI - The detection of ventricular dysfunction and carditis in children with Kawasaki disease using equilibrium multigated blood pooling ventriculography and 99Tcm HMPAO-labelled WBC heart scans. AB - Thirty-seven children (11 girls, 26 boys; aged 2.8 +/- 2.2 years) with Kawasaki disease (KD) were included in the study. The biventricular functions were evaluated by equilibrium multigated blood pooling ventriculography (EMBPV) and the severity of carditis was decided by Tc-hexamethylpropyleneamine oxime (HMPAO) labelled white blood cell (WBC) heart scans (Tc-WBC). The results showed that 43% (16/37) of the KD cases with the severe carditis by Tc-WBC had the worst left ventricular ejection fraction (LVEF) (55.4 +/- 15.6%) and right ventricular ejection fraction (RVEF) (43.7 +/- 12.2%) by EMBPV; 24% (9/37) of the cases with the mild carditis had the best LVEF (63.5% +/- 8.2%) and RVEF (53.7% +/- 11.2%); the remaining 32% (12/37) had moderately severe carditis and biventricular function (LVEF: 58.2 +/- 17.2% and RVEF: 46.9 +/- 19.5%). Because Tc-WBC cannot only detect the severity of carditis but also predict impairment of ventricular function accurately, the choice of Tc-WBC should be preferable for KD-a common inflammatory cardiovascular disease in children. PMID- 8355913 TI - An alternative method for rapid preparation of 99Tcm-sestamibi. AB - The availability of 99Tcm-sestamibi is limited, especially in emergency cases due to the time-consuming preparation procedure that requires a 10-min boiling water bath and a 30-min radiochemical purity (RCP) analysis. These two restrictions have been surmounted by the combined use of a microwave oven heating method and a minipaper chromatography system. However, use of the microwave oven heating method presents some potential problems: (1) technical error in setting the microwave oven heating time and power setting; (2) ejection of the rubber septum if the vial is not evacuated; (3) breakage of the vial during the microwave heating process; (4) inconsistent and inhomogeneous microwave heating; (5) reevaluation process required for use of a different type of microwave oven. Although a 1-min boiling water bath time is sufficient to provide an acceptable RCP for 99Tcm-sestamibi, additional time is required to heat the water to a boiling state. An instant hot water machine was evaluated for possible replacement of the microwave heating method. Three millilitres of 5500 MBq (150 mCi) 99Tcm was added to a Cardiolite kit and then placed in a 150-ml insulated beaker filled with hot water (86.2 +/- 1.9 degrees C, n = 45) from an instant hot water machine. A minipaper chromatography system was used to determine the RCP of samples after 1, 1.5, 2, 3, 4 and 5 min incubation periods. Our results show that 2 min was the shortest incubation time that yielded an acceptable RCP of 94.7 +/- 0.4% (n = 60) over the 24 h evaluation time. The use of an instant hot water machine not only avoids those problems associated with the microwave heating method, but also provides a rapid, efficient and relatively simple option for preparation of 99Tcm-sestamibi. PMID- 8355914 TI - Somatostatin receptors in meningiomas: a scintigraphic study using 111In-DTPA-D Phe-1-octreotide. AB - 111In-octreotide (Octreoscan) planar scintigraphy was performed in 12 patients with suspected meningioma. The scan was positive in 10 patients with meningioma and negative in two patients with acoustic neurinoma assisting in the differential diagnosis. Good quality images were obtained as early as 2 h after injection and there was no increase in diagnostic quality at 24 h. No adverse effects were observed to radiopharmaceutical administration. The following conclusions are drawn: 111In-octreotide is a safe and fast test which can increase the specificity of traditional neuroimaging procedures. PMID- 8355915 TI - A method to improve the quality of bone marrow scintigraphy by scatter radiation correction with the use of two opposing views. AB - Bone marrow scintigraphy using radiocolloids labelled with 99Tcm allows imaging of the active marrow with moderate effort. However, most of the administered colloid is trapped in the liver and spleen giving rise to a considerable amount of scattered photons, which cause considerable problems when evaluating the adjacent bone marrow. There are scatter correction methods developed for single photon emission computed tomography. The application of such a technique to bone marrow scintigraphy in the liver region using two opposing views is described. Phantom measurement and patients studies show that substantially improved visualization of the bone marrow close to the liver is possible using this technique for scatter correction. PMID- 8355916 TI - 99Tcm-MDP global skeletal uptake and markers of bone metabolism in patients with bone diseases. AB - 99Tcm-methylene diphosphonate (MDP) global skeletal uptake (4 h GSU) was determined by quantitative measurement of activity on bone scan images 4 h after injection in whole skeleton regions of interest (ROI) in 16 normal subjects, in five patients with hypertrophic pulmonary osteoarthropathy (HPO) and in 12 with Paget's disease. Values were correlated with those of whole body retention (24 h WBR), and serum bone gla protein (BGP), i.e. osteocalcin, alkaline phosphatase (AP) and type 1 procollagen (P1CP). They were 40% higher in HPO than in the normal controls, while in Paget's disease they increased more in polyostotic than in monostotic patients. A statistically significant difference was noted between 4 h GSU and 24 h WBR values in the two groups of patients compared with the controls. Of the bone metabolism markers, serum AP and P1CP were higher in the patients and positively correlated with their enhanced 4 h GSU values, whereas BGP was always within the normal range. This method may thus be regarded as a useful way of simultaneously determining bone 99Tcm-MDP uptake and altered bone turnover sites, especially in patients with systemic bone disease. PMID- 8355917 TI - Dose response from pharmacological interventions for CBF changes in a baboon model using 99Tcm-HMPAO and SPECT. AB - This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and 99Tcm hexamethylpropyleneamine oxime (HMPAO) dose responses from drugs (acetazolamide) with known regional cerebral blood flow (rCBF) effects on humans. Three dosages of acetazolamide were chosen: 250, 500 and 750 mg. The effects of these were studied by conventional SPECT 5 min after intravenous (i.v.) administration and compared to previous studies of rCBF with the baboons under anaesthesia only. An additional study concerned the effect of 500 mg acetazolamide at 15 min after administration. Haemodynamic parameters and blood gases were also monitored. No statistically significant regional effects were noted (P > 0.05). The largest increase in CBF (39%) was observed from 500 mg acetazolamide after 5 min. This was statistically significantly different from control values only at a 10% level of confidence; then followed a 27% increase above control values after 750 mg (5 min). At 15 min 500 mg yielded values lower by 10% than the high dose. No effects were observed from 250 mg acetazolamide; only pO2 showed changes which largely confirm the CBF findings. The model did not give significant results at a 5% level of confidence but large fluctuations were observed, also in the haemodynamic and blood gas values. At a 10% level a significant dose response was confirmed for acetazolamide. PMID- 8355918 TI - Immunoscintigraphy of ovarian carcinoma using a monoclonal antibody (111In NCRC48) defining a polymorphic epithelial mucin (PEM) epitope. AB - An anti-polymorphic epithelial mucin (PEM) monoclonal antibody NCRC48 (IgG3) has been tested for its capacity to localize in tumours according to accepted guidelines for human administration. Following radiolabelling with 111In, 1 mg antibody was administered to 19 patients with a clinical suspicion of ovarian malignancy. Initial imaging and biodistribution studies confirm the safety of this conjugate although six out of 11 patients tested developed an antibody response to the monoclonal antibody. Immunoscintigraphy with this antibody was compared with magnetic resonance imaging and ultrasound in relation to the final tumour histology, the final accuracies being 79, 79 and 64% respectively. Positive localization of antibody was confirmed in malignant tissue with little evidence of uptake in benign tissue. PMID- 8355919 TI - Body and blood clearance and marrow radiation dose of 131I-Lym-1 in patients with B-cell malignancies. AB - Fifty-eight per cent of patients with B-cell malignancies had durable responses to treatment with 131I-Lym-1. Myelosuppression manifested by peripheral blood cytopenia was the radiation dose-limiting toxicity. The mean biologic half-times were 3.3 and 31.2 h for the fast and slow phases, respectively, of the blood clearance and 33.5 h for the clearance from the total body. Nonpenetrating radiation from the blood contributed 0.18 rad and penetrating radiations from the total body contributed 0.18 rad per administered mCi to the bone marrow. The average total contribution from both of these sources was 0.36 +/- 0.14 rad mCi 1. Clearances and marrow radiation doses were remarkably constant among different patients and among different therapy doses for the same patient. These results are potentially useful as an initial approximation for other mouse monoclonal antibodies of the same isotype. While radiation to normal marrow from 'spill over' incident to specific targeting of 131I-Lym-1 on malignant B-cells in the marrow is not addressed in this publication because it is unique for each patient, it should be considered in the case of individual patients. PMID- 8355920 TI - Pancreatic cancer detected by positron emission tomography with 18F-labelled deoxyglucose: method and first results. AB - In order to evaluate the utility of positron emission tomography (PET) with 18F labelled deoxyglucose (FDG) for detection of pancreatic cancer 15 patients with pancreatic masses shown by computed tomography were investigated. Static PET scans covering an axial field of view of 15 cm were obtained 45 min after intravenous injection of 150-300 MBq FDG. Focally increased FDG accumulation was present in 12 out of 13 patients with histologically proven adenocarcinoma, in particular in eight of nine lymph node and four of five liver metastases. Scans of two patients with chronic pancreatitis confirmed by surgery revealed a normal FDG distribution. Contrast between tumour and normal tissue depended the metabolic situation prior to FDG injection. High ratios were found in fasting patients whereas no elevated FDG uptake was measured in an insulin-dependent diabetic suffering from carcinoma of the pancreatic head. We conclude that FDG PET might have the potential for detection and even differentiation of pancreatic carcinoma from chronic pancreatitis. Further studies are necessary to substantiate these preliminary findings and to optimize results in diabetic patients. PMID- 8355921 TI - In vivo determination of radiation dose in kidneys and bladder during renogram: a new approach. AB - The radiation dose absorbed by a patient from a radiopharmaceutical is usually calculated with the help of the equations published by the Society's Medical Internal Radiation Dose (MIRD) Committee and the use of a Reference Man. However, the (MIRD) estimations are based on the assumption that the patient is a normal subject with the characteristics of the Reference Man. This is not always true particularly in some pathological situations which present large deviations from normal. The purpose of this paper is to determine the dose in kidneys and bladder, during renograms, on the basis of real data. A protocol is formulated by means of which the processing of the frames acquired in the various stages of the renogram enables the determination of the kidney and bladder mass as well as the time distribution of radioactivity in these organs. Our results are in accordance with MIRD estimations for normal cases, whereas very significant deviations are observed in pathological ones. This is due to the fact that the mass of the 'source' and 'target' organs as well as the biodistribution of the radiopharmaceuticals are essential in the dose determination and large deviations are expected between estimated and real doses when in some pathological cases the mass of kidney is particularly reduced or its clearance retarded. PMID- 8355922 TI - Letter from the Mayo Clinic. PMID- 8355923 TI - The Human Genome Project: impact on obstetrics and gynecology. PMID- 8355924 TI - Prostaglandin synthetase inhibitors in pregnancy. AB - The use of indomethacin as a tocolytic agent in patients with premature labor was first reported by Zuckerman in 1974. Since then, prostaglandin synthetase inhibitors (PSI) have been used in pregnancy for a variety of indications. However, serious fetal side effects of this category of drugs continue to be reported. We present a review of the literature and the experience at our institution on the use of indomethacin, the most commonly prescribed antiprostaglandin in pregnancy. Therapeutic guidelines and surveillance recommendations for the use of PSI in pregnancy are proposed. The role of newer PSI in pregnancy and their side effect profile are also presented. PMID- 8355925 TI - Percutaneous balloon valvuloplasty for severe mitral stenosis during pregnancy: a review of therapeutic options. AB - A woman presented at 29 weeks' gestation with previously undiagnosed severe mitral stenosis. She did not respond to medical therapy, and underwent successful percutaneous balloon mitral valvuloplasty with complete resolution of her symptoms. The remainder of her pregnancy was uncomplicated, and she delivered a healthy infant at 40 weeks' gestation. Percutaneous balloon valvuloplasty offers an innovative alternative to standard surgical therapy if medical management is unsuccessful. PMID- 8355927 TI - Randomized comparison of home uterine activity monitoring and routine care in patients discharged after treatment for preterm labor. AB - OBJECTIVE: To determine whether home uterine activity monitoring reduces the likelihood of preterm birth in women successfully treated for preterm labor in their current pregnancies. METHODS: Women between 20-34 weeks' gestation who had been treated successfully for preterm labor were solicited to participate in a randomized clinical trial of home uterine activity monitoring versus routine high risk care. The sample size of 56 was based on power calculations using the results of earlier investigators. Twenty-eight women were randomized to home uterine activity monitoring and 29 were assigned to the type of care appropriate for women discharged after hospitalization for parenteral treatment of preterm labor. One of the routine-care subjects was lost to follow-up. The two groups were comparable in distribution for race, insurance status, multiple gestation, marital status, gestational age at beginning of the study, and incidence of prior preterm birth. RESULTS: The 28 women receiving routine care had a 54% incidence of preterm birth, whereas the incidence was 57% in monitored women (relative risk 1.08, 95% confidence interval 0.6-1.9; P = .79). The incidences of delivery before 32 weeks and 34 weeks also were unaffected by the intervention. CONCLUSION: Home uterine activity monitoring is not effective in reducing the likelihood of preterm delivery in patients successfully treated for preterm labor in their current pregnancies. PMID- 8355926 TI - Estrogen effects on the urethra: beneficial effects in women with genuine stress incontinence. AB - The urethra, which originates from the urogenital sinus, is under the influence of estrogen just like the vagina. The concentration of estrogen receptors in the urethral mucosa is similar to that of the vaginal mucosa. Estrogen deprivation will result in atrophic urethritis and sometimes urinary incontinence, and estrogen replacement therapy may reverse this trend. Estrogens have been shown to increase urethral pressure in up to 30 per cent of women and to significantly improve or cure stress urinary incontinence in many cases. Adding alpha sympathomimetic drugs to estrogens may further improve symptoms in women with stress incontinence. It seems that vaginal estrogens have more beneficial effect on the urethra, compared with the oral medication, although prospective control studies have not always supported these findings. Overall, it seems that estrogens have beneficial effects on urethral function in women with postmenopausal stress incontinence, although more prospective randomized control studies are needed to assess the effect of estrogens on the lower urinary tract. PMID- 8355928 TI - Pregnancy in heart transplant recipients: management and outcome. AB - OBJECTIVE: To determine the outcome of pregnancies in cardiac allograft recipients. METHODS: Thirty women who became pregnant after heart transplantation were identified from cases managed personally, questionnaires sent to all cardiac transplant centers, and review of the literature. Mothers were evaluated for evidence of rejection and for obstetric complications. The infants were observed for congenital abnormalities and perinatal morbidity or mortality. RESULTS: Frequent pregnancy complications included chronic hypertension (48%), preeclampsia (24%), and preterm labor (28%). The rate of cesarean delivery was 32%. Six episodes of rejection required treatment, and three late maternal deaths occurred. Among the 27 live births, 17 infants were born after 36 weeks' gestation and ten were preterm, five were small for gestational age, and four had neonatal complications. There were no congenital anomalies. CONCLUSION: Pregnancies in heart transplant recipients present management problems similar to those seen in patients with other allografts and should be considered high risk. PMID- 8355929 TI - A randomized, double-blind, placebo-controlled trial of the safety of vaginal recombinant human relaxin for cervical ripening. AB - OBJECTIVE: To assess the safety of vaginal recombinant human relaxin in pregnant women treated before the induction of labor and to collect preliminary data on the efficacy of recombinant human relaxin in promoting cervical ripening. METHODS: In a multi-center, randomized, double-blind placebo-controlled trial, 40 women were studied before induction of labor because of post-dates. The women were randomized to receive either 1.5 mg recombinant human relaxin in 3% methylcellulose gel or gel only, placed into the posterior vaginal fornix after a cervical assessment on the evening before scheduled induction. If a subject did not go into spontaneous labor overnight, another cervical assessment was performed 15 hours following treatment, immediately before the standard induction regimen of the hospital. RESULTS: No important maternal or fetal-neonatal complications could be attributed to the drug. The differences between the recombinant human relaxin group and the placebo group for all the outcome measures of efficacy did not achieve statistical significance. Placebo patients were more likely to report moderate or strong uterine contractions in the first 4 hours following treatment than were the recombinant human relaxin-treated patients. CONCLUSIONS: The use of recombinant human relaxin at a dose of 1.5 mg was not associated with any significant maternal or fetal-neonatal complications. The relatively small number of subjects in this study was chosen deliberately because this was the first use of the drug in pregnant subjects. Assessment of efficacy will require studies that include more patients and a range of relaxin doses. PMID- 8355930 TI - Peripartum changes in maternal cerebral blood flow velocity in normotensive and preeclamptic patients. AB - OBJECTIVE: To compare the effect of delivery on cerebral blood flow velocity between normotensive and preeclamptic women, adjusting for mode of delivery and change in hematocrit values. METHODS: Twenty-three normotensive and 46 preeclamptic women had maternal middle cerebral blood flow velocity assessed antepartum and at 24 and 48 hours postpartum. In addition, hematocrit changes and method of delivery were recorded. We then compared the effect of delivery on cerebral blood flow velocity changes using analysis of variance with Student t test for significance. RESULTS: Cerebral blood flow velocity was significantly higher in preeclamptic than in normotensive women (P < .05) and rose significantly in the postpartum period (P < .004). Neither hematocrit change nor mode of delivery affected cerebral blood flow velocity changes. CONCLUSION: Cerebral blood flow velocity showed minimal peripartum changes in the normotensive group but increased significantly postpartum in preeclamptic women in a setting of minimal arterial pressure change. PMID- 8355931 TI - Penicillin levels following the administration of benzathine penicillin G in pregnancy. AB - OBJECTIVE: To investigate the distribution of penicillin in the maternal placental-fetal unit at term gestation. METHODS: Twenty-five healthy gravidas at 38-39 weeks' gestation scheduled for elective repeat cesarean delivery under spinal anesthesia received benzathine penicillin G, 2.4 million units intramuscularly (IM) preoperatively. Ten women delivered 1 day after injection, five delivered 2-3 days after, and ten delivered 7 days after. We collected maternal serum and cerebrospinal fluid, amniotic fluid (AF), and cord serum at delivery. Penicillin levels were measured using a validated agar disc diffusion method (sensitivity 0.006 micrograms/mL) with Micrococcus lutea as the test organism. RESULTS: There was no significant difference in mean penicillin levels at day 1, day 2-3, or day 7 for maternal serum, maternal cerebrospinal fluid, cord serum, or AF. The mean (+/- standard error) penicillin concentration (range 0.005-0.59 micrograms/mL) in maternal serum declined from 0.14 +/- 0.04 micrograms/mL 1 day after injection to 0.08 +/- 0.06 micrograms/mL 7 days after injection. The proportion of patients with a penicillin concentration at or above 0.018 micrograms/mL in the maternal serum declined significantly from day 1 to day 7 (P = .03). Overall, nine of 25 women (36%) had serum penicillin levels that were less than 0.018 micrograms/mL. CONCLUSION: A wide range of penicillin levels were observed in gravidas at term in the maternal serum, cerebrospinal fluid, umbilical cord serum, and AF within 1 week after 2.4 million units of benzathine penicillin G IM. We speculate that altered pharmacokinetics may affect the efficacy of this drug for prevention of congenital syphilis in the near-term gestation. PMID- 8355932 TI - Prenatal use of metronidazole and birth defects: no association. AB - OBJECTIVE: To determine whether the use of metronidazole by pregnant women increases the risk of birth defects in the offspring. METHODS: Two cohorts of pregnant women who delivered live-born or stillborn infants between January 1, 1983 and December 31, 1988 were identified from the Tennessee Medicaid enrollment files. The exposed cohort consisted of 1387 women who filled a prescription for metronidazole between 30 days before and 120 days after the onset of their last normal menstrual period. The unexposed cohort consisted of 1387 comparable women who did not fill a prescription for metronidazole during the same time. Medical records for 94% of the offspring of both study cohorts were then reviewed to ascertain the occurrence of birth defects. RESULTS: Pregnancy outcomes were similar for the exposed and unexposed cohort members. There was no excess of overall birth defect occurrence in the offspring of exposed women (risk ratio 1.2, 95% confidence interval 0.9-1.6), nor could an excess risk be detected for any category of birth defects. CONCLUSION: This study provides no evidence that prenatal use of metronidazole increases the risk of overall birth defect occurrence. PMID- 8355933 TI - Erythropoietin in human fetuses with immune hemolytic anemia and hydrops fetalis. AB - OBJECTIVE: To determine whether plasma erythropoietin is increased in fetuses with anemia due to Rh isoimmunization. METHODS: Hemoglobin and erythropoietin were measured in samples obtained by funipuncture from 15 fetuses with Rh isoimmunization (gestational age 26.2 +/- 5.0 weeks, mean +/- standard deviation) and from 13 control fetuses (23.1 +/- 6.7 weeks). Hemoglobin and erythropoietin also were determined in umbilical cord blood collected at birth from 20 term fetuses delivered by elective cesarean. RESULTS: Fetuses with Rh isoimmunization had lower hemoglobin and higher plasma erythropoietin measurements than mid gestation controls (6.1 +/- 3.9 versus 10.7 +/- 1.5 g/dL and 105.5 +/- 168.1 versus 12.5 +/- 3.1 mU/mL, P < .05, respectively). Hemoglobin and plasma erythropoietin increased with gestational age in control fetuses. There was an inverse association between hemoglobin and plasma erythropoietin in control and Rh-isoimmunized fetuses (r = -0.56, P < .005). Using multiple linear regression, hemoglobin and gestational age were associated independently with plasma erythropoietin (overall F2,25 = 12.3, multiple r2 = 0.49, P < .001). Despite marked decreases in hemoglobin, fetuses below 24 weeks' gestation had minimal increases in plasma erythropoietin compared to fetuses above that gestational age. Mildly anemic Rh-isoimmunized fetuses (hemoglobin 11.6 +/- 2.0 g/dL) delivered vaginally had significantly higher erythropoietin levels in umbilical cord plasma than Rh-isoimmunized fetuses with comparable hemoglobin (10.9 +/- 3.5 g/dL) delivered by elective cesarean without labor (1246 +/- 856 versus 106 +/- 66 mU/mL, respectively, P < .05). CONCLUSION: Fetuses with anemia at mid to late gestation respond with increases in plasma erythropoietin, but these changes are substantially attenuated before 24 weeks' gestation. PMID- 8355934 TI - Ultrasonic estimation of fetal weight: use of targeted formulas in small for gestational age fetuses. AB - OBJECTIVE: To derive a formula for calculating fetal weight in small for gestational age (SGA) fetuses and to determine prospectively whether the use of such a targeted formula reduces birth weight prediction errors. METHODS: Standard ultrasonic measurements were made in 159 SGA fetuses within 7 days of delivery. Three classes of fetal weight formulas (linear, quadratic, and cubic) were fitted to the data using stepwise regression analysis. Birth weight predictions using these three formulas were then compared prospectively with five previously reported formulas in 187 SGA fetuses. RESULTS: R2 was 0.97 for each of the three derived formulas. The 95% prediction intervals were comparable for the three formulas (eg, cubic model -11.6, 17.8%), and none were statistically superior to previous formulas. Each of the formulas evaluated prospectively had a systematic error and, with the exception of the present study's linear formula, all had percentage errors that varied systematically over the range of actual birth weights. CONCLUSION: Clinically useful birth weight predictions can be made in SGA fetuses, although no particular formula estimates birth weight significantly more accurately than any other. PMID- 8355935 TI - Sonographic estimation of fetal weight based on a model of fetal volume. AB - OBJECTIVES: To derive a formula for sonographic estimated fetal weight (EFW) based on a two-compartment model of fetal volume and to test it against two widely used formulas, especially at the extremes of fetal weight for which existing formulas are generally inaccurate. METHODS: We analyzed 865 consecutive sonograms that met the following inclusion criteria: singleton pregnancy, normal anatomy, delivery within 3 days of sonography, and measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The weight of the fetal head was modeled to be proportional to HC3, and the weight of the trunk proportional to AC2 x FL. The proportionality constants were found by multiple linear regression on 380 sonograms performed in 1990 (the "derivation set"). The new formula was tested for accuracy of prediction of actual birth weight against the formulas of Hadlock et al and Shepard et al using 485 sonograms from 1991-1992 (the "validation set"). RESULTS: In the derivation set, the formula EFW = (0.23718 x AC2 x FL) + (0.03312 x HC3) was fit; the correlation with actual birth weight had an r value of 0.996. In the validation set, the new formula produced smaller systematic errors and smaller absolute errors than either the Hadlock or Shepard formula both overall and in fetal weight strata from less than 1000 g to over 4000 g. CONCLUSION: The new formula makes geometric sense and provides accurate estimates of fetal weight across a broad range of weights. PMID- 8355936 TI - The use of vibroacoustic stimulation during the abnormal or equivocal biophysical profile. AB - OBJECTIVE: To determine whether vibroacoustic stimulation during the biophysical profile can change the fetal behavioral state and thus improve the score without increasing the false-negative rate of the test. METHODS: Eighty-one patients whose biophysical profile scores were 6 or lower after 15 minutes of observation had an electronic artificial larynx applied to the maternal abdomen in the region of the fetal head for 3 seconds, followed by continued observation for fetal movement, tone, and breathing for 15 minutes. We compared the obstetric and neonatal outcomes of 41 patients whose biophysical profile scores improved to normal after vibroacoustic stimulation with those of 283 patients whose scores were normal without vibroacoustic stimulation. RESULTS: Vibroacoustic stimulation did improve an abnormal or equivocal biophysical profile score to normal in 67 of 81 cases (82%). No antepartum stillbirths or perinatal deaths occurred. There was no increase in the obstetric and neonatal complication rates of cesarean delivery for fetal distress, meconium staining of the amniotic fluid, and the incidence of small for gestational age infants. CONCLUSION: Vibroacoustic stimulation improved the biophysical profile scores in most cases, an effect seen throughout the third trimester. Vibroacoustic stimulation did not appear to increase the false negative rate of the biophysical profile and may reduce the incidence of unnecessary obstetric intervention. PMID- 8355937 TI - Phenytoin and magnesium sulfate effects on fetal heart rate tracings assessed by computer analysis. AB - OBJECTIVE: To compare the effects of maternally administered phenytoin and magnesium sulfate on the fetal heart rate (FHR) using computer analysis. METHODS: Thirty-six nonlaboring preeclamptic women between 27-41 weeks' gestation were treated with either phenytoin or magnesium sulfate in a nonrandomized fashion. All fetuses were deemed to be well by traditional electronic-biophysical criteria. One-hour FHR recordings were analyzed by computer analysis before treatment. No other medications were administered. Tracings recorded 1 hour after drug administration were analyzed. Therapeutic serum levels were achieved in both groups before FHR tracings were reevaluated. Statistical analysis used paired Student t test, with significance set at P < or = .05. RESULTS: There were no differences in birth weight, gestational age, Apgar scores, or computer-analyzed FHR characteristics between the groups before treatment. Magnesium sulfate reduced significantly the frequency of accelerations of ten and 15 beats per minute; caused a 62% reduction in reactivity, defined as accelerations of 15 beats per minute in 20 minutes of FHR tracing (but no change in reactivity with accelerations of ten beats per minute); and reduced short- and long-term variability. Phenytoin reduced short-term variability only. CONCLUSION: Phenytoin does not confound the computer analysis of FHR tracings and may offer some advantage over magnesium sulfate when used for prophylaxis against eclampsia. PMID- 8355938 TI - The effect of vaginal dissection on the pudendal nerve. AB - OBJECTIVE: To determine the effect of vaginal dissection on the pudendal nerve. METHODS: Pudendal and perineal nerve terminal motor latencies were measured before and at least 6 weeks after either abdominal or vaginal surgery for genital tract prolapse with or without urinary and fecal incontinence. Forty-eight women were studied prospectively in a randomized, blinded fashion. RESULTS: All women in this study had pelvic floor prolapse, and their mean preoperative pudendal and perineal nerve terminal motor latencies were prolonged compared to previously established normal values. The 27 women undergoing vaginal dissection demonstrated significant mean increases in pudendal nerve terminal motor latency (0.63 milliseconds, 95% confidence interval [CI] 0.33-0.93; P = .001) and perineal nerve terminal motor latency (1.33 milliseconds, 95% CI 0.80-1.86; P = .0001). In the 21 who had abdominal operations without vaginal dissection, essentially no mean change was noted. Clinically significant increases (more than 2 standard deviations) in pudendal or perineal nerve terminal motor latency occurred in 20 women (74%) in the vaginal dissection group and in seven women (33%) in the abdominally operated group. The odds ratio of producing such neuropathy by vaginal dissection compared to operating abdominally without vaginal dissection was 5.78 (95% CI 1.6-20). CONCLUSIONS: All women had abnormal preoperative pudendal nerve function, supporting previous reports linking pudendal neuropathy with pelvic floor prolapse. Pelvic floor surgery involving vaginal dissection produces neuropathy of the pudendal nerve as measured by terminal motor latency. PMID- 8355939 TI - Cosmetic result of lower midline laparotomy wounds: polybutester and nylon skin suture in a randomized clinical trial. AB - OBJECTIVE: To compare the cosmetic outcome of lower midline laparotomy scars using either nylon or polybutester suture for skin closure. METHODS: A randomized clinical trial compared polybutester skin suture with nylon for lower midline laparotomy wounds in 50 women undergoing gynecologic surgery. Scar hypertrophy, scar width, scar color, the presence of cross-hatching marks, and a total score were assessed in all patients at 18 months following surgery and compared by nonparametric statistical tests. RESULTS: The wounds closed with polybutester suture were significantly less hypertrophic than those closed with nylon. Regardless of the suture material used, the lower part of the laparotomy scar showed an inferior cosmetic result compared with the upper part underneath the umbilicus for scar hypertrophy, scar width, and the total scar score. CONCLUSIONS: Polybutester skin suture diminishes the risk of hypertrophic scarring because of its special properties allowing it to adapt to changing tensions in the wound. Increased closure tension of the skin in the midline region above the pubic bone may be caused by a relative immobility of the skin. Scar cosmetics in this area may be improved by extra subcuticular suture support. PMID- 8355940 TI - Cervical conization with frozen section before planned hysterectomy. AB - OBJECTIVE: To report our institutional experience with the accuracy and usefulness of cervical conization with frozen section before planned hysterectomy. METHODS: One hundred fifty-nine patients who planned to have hysterectomies for or with a concomitant diagnosis of cervical intraepithelial neoplasia (CIN) underwent preliminary cone biopsies with frozen section. The frozen and permanent pathologic diagnoses were compared retrospectively. Detailed analysis was directed at the indications for cone biopsy and the patients who were found to have invasive cancer. RESULTS: Among 108 patients with negative specimens or CIN, the frozen section was accurate within one degree of CIN in 106. Cone biopsy for a positive endocervical curettage, unsatisfactory colposcopy, or discrepant cytology did not contribute to the diagnosis of invasive cancer but did lead to an ultimate diagnosis of CIN III. One of 12 women with a frozen-section diagnosis of microinvasion had deeper invasion on permanent sections. CONCLUSIONS: Frozen-section evaluation of a cone biopsy carries a degree of accuracy that enables the surgeon to make an immediate decision about definitive therapy. Exact indications, use during pregnancy, and accuracy for the diagnosis of microinvasion require further study. PMID- 8355941 TI - Strategy for screening pregnant women for chlamydial infection in a low prevalence area. AB - OBJECTIVE: To assess the prevalence and risk factors for chlamydial infection in pregnant women in the Quebec City area and to propose strategies for a screening program. METHODS: From January 1990 to July 1991, pregnant women from six centers were cultured for Chlamydia trachomatis. One hundred thirty-six with positive results and 536 with negative results were included in a case-control study on risk factors for this infection. RESULTS: The prevalence of C trachomatis was 1.9% (136 of 7305). In a logistic regression analysis, young age (P < .0001, test for trend), nulliparity (odds ratio [OR] 3.3; P < .00001), and a new sexual partner in the last year (OR 3.3; P = .0012) were independently associated with infection. With screening restricted to pregnant women under age 25 or those with at least one risk factor, 81.7% of women positive for C trachomatis would have been detected, whereas only 40.6% of all women would have been cultured. CONCLUSION: In a low-prevalence area for chlamydial infection in pregnant women, pre-screening criteria could optimize the use of specific diagnostic tests. PMID- 8355942 TI - Efficacy of clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis. AB - OBJECTIVE: To compare the efficacy and tolerance with 2% clindamycin vaginal cream versus oral metronidazole for the treatment of bacterial vaginosis. METHODS: This was a multicenter, randomized, double-blind study in which patients were randomly assigned to one of the following two regimens in a 1:1 ratio: clindamycin phosphate vaginal cream 2% (5 g intravaginally at bedtime for 7 days) plus two placebo capsules (twice a day for 7 days) or metronidazole 500 mg (two 250-mg capsules orally twice a day for 7 days) plus placebo vaginal cream (5 g intravaginally at bedtime for 7 days). The patients were seen for follow-up at 5 10 days and 25-39 days after completion of therapy. RESULTS: Seven investigators, four in Germany, two in Austria, and one in Switzerland, enrolled 407 patients. Four patients never received either protocol drug, leaving 403 evaluable for safety. Two hundred thirty-four patients were evaluable for efficacy. The analysis for all evaluable patients showed no significant difference between treatment groups. The cure or improvement rate at 1 month after therapy was 83% in the clindamycin group versus 78% in the metronidazole group. The incidence of drug-related adverse medical events was approximately 12% in both groups. CONCLUSIONS: Oral metronidazole and intravaginal clindamycin cream had a similar efficacy of 78 to 83%. Both drugs were tolerated, with vaginal candidiasis developing in 8.5 and 4.7% of the patients in the clindamycin and metronidazole groups, respectively. PMID- 8355943 TI - The effect of same-day pregnancy testing on the incidence of luteal phase pregnancy. AB - OBJECTIVE: To assess the impact of same-day pregnancy testing on the incidence of luteal phase pregnancy (pregnancy in which conception occurs before sterilization). METHODS: Retrospectively, all patients (N = 1006) undergoing laparoscopic tubal ligations at the Regional Medical Center, Memphis, from May 1990 through December 1991 were reviewed for sterilization failures. Negative urine pregnancy tests were documented on all scheduled patients at their preoperative examination. After the first 401 sterilizations, same-day pregnancy testing with enzyme-linked immunosorbent assay (ELISA) pregnancy tests was instituted. We reviewed the records of all presumed sterilization failures as well as all patients with a positive pregnancy test on the day of surgery. Last menstrual period, ultrasound records, and date of delivery were analyzed to determine time of conception. RESULTS: Seven luteal phase pregnancies were discovered among the first 401 sterilization cases (17 per 1000). No luteal phase pregnancies occurred in the next 605 sterilizations after institution of same-day pregnancy testing. Eight patients' sterilizations were canceled because of a positive pregnancy test on the morning of surgery. If these patients had not been eliminated, the incidence of luteal phase pregnancies in this second group would have been 13 per 1000 sterilization procedures. CONCLUSION: Same-day pregnancy testing with an ELISA-type pregnancy test is a rapid, inexpensive, and effective means of reducing the incidence of luteal phase pregnancy. PMID- 8355944 TI - Diagnostic and operative hysteroscopy in the management of persistent postmenopausal bleeding. AB - OBJECTIVE: To determine the cause and possible treatment of postmenopausal bleeding of 6 months' duration or longer. METHODS: One hundred ten women between the ages of 40-90 years with persistent postmenopausal bleeding were evaluated by diagnostic hysteroscopy and managed by operative hysteroscopy. All had endometrial sampling and/or office hysteroscopy before operative hysteroscopy. RESULTS: A benign organic cause was noted in 95 cases (polyps in 42 and submucous fibroids in 53). Thirteen women had no significant disease and two had an early adenocarcinoma. Resection of the polyps or myomas without ablation was performed in 45 women, and all but one were satisfied with the results of treatment. Resection and ablation with performed in the remaining 50 patients with organic causes, and all but one were satisfied with the results. Twelve of 13 women without organic causes were satisfied with their treatment. The two adenocarcinomas were early lesions, grade 1 without invasion, and were managed by simple hysterectomy. CONCLUSION: Diagnostic and operative hysteroscopy was effective in controlling postmenopausal bleeding of at least 6 months' duration. Almost 90% of the patients had either polyps or submucous fibroids as the primary cause of the bleeding. Resection alone and resection with ablation were equally effective in controlling the bleeding. PMID- 8355945 TI - Post-ablation-tubal sterilization syndrome. AB - OBJECTIVE: To determine the cause of unilateral or bilateral pelvic pain associated with vaginal spotting in women who had previously undergone tubal ligation followed by roller-ball endometrial ablation. METHODS: Women who had undergone previous tubal sterilization followed by rollerball endometrial ablation were evaluated laparoscopically and hysteroscopically when they presented with a symptom complex of intermittent vaginal bleeding associated with severe cramping pain in the lower abdomen. RESULTS: During a 1.5-year observation period, six women with the symptom complex had laparoscopy and hysteroscopy. In all cases, marked endometrial scarring was noted. In every case, the proximal portions of either one or both fallopian tubes were swollen, and two cases had the appearance of an early ectopic pregnancy. In the remaining cases, the fallopian tubes were rubbery and swollen to as much as twice normal size. Symptoms in five of six patients subsided after laparoscopic removal of the oviduct. CONCLUSION: It appears that women who have had a tubal sterilization followed by endometrial ablation are at risk of developing an ectopic-like symptom complex. Salpingectomy appears to be effective in relieving symptoms. Whether this represents a new syndrome or just an unusual association between tubal sterilization and endometrial ablation remains to be seen. PMID- 8355946 TI - Accuracy of the Papanicolaou smear in the diagnosis of asymptomatic infection with Trichomonas vaginalis. AB - OBJECTIVE: To assess the accuracy of Papanicolaou smears in reporting cytologic evidence of Trichomonas vaginalis in asymptomatic women attending a resident clinic. METHODS: In phase I of this study, we prospectively enrolled 100 asymptomatic gynecologic patients to be screened for vaginal trichomoniasis using wet preparation, vaginal culture, and Papanicolaou smear. During phase II, asymptomatic patients (40 gynecologic and 20 obstetric) whose screening Papanicolaou smears showed cytologic evidence of trichomoniasis returned for wet preparation, culture, and repeat Papanicolaou smear. Patients were considered infected with T vaginalis if either the wet preparation or culture was positive, and uninfected if both tests were negative. The cytopathologist was not informed of the patient's enrollment in this study or of the results of culture or wet preparation. RESULTS: The prevalence of asymptomatic trichomonas infection in gynecologic patients enrolled in phase I was 6%. In asymptomatic gynecologic patients enrolled in phase II, repeat Papanicolaou smear had a sensitivity and specificity of 86 and 83%, respectively, when diagnosing infection. Thirty percent of these patients would have been treated unnecessarily for trichomoniasis based upon screening Papanicolaou smear. In obstetric patients, the sensitivity of repeat Papanicolaou smear was 94% and specificity was 100%. Had therapy been initiated based on screening cytology, 20% of obstetric patients would have received unindicated therapy. The differences in sensitivity and specificity between the groups were statistically significant (P < .05). CONCLUSION: When a screening Papanicolaou smear reports cytologic evidence of T vaginalis infection in the asymptomatic patient, a confirmatory test should be performed before initiating therapy. PMID- 8355947 TI - The mode ages of women with cervical dysplasia. AB - OBJECTIVE: To resolve the discrepancy that women seem to have Papanicolaou smears with dysplasia at younger ages than the reported mean ages. METHODS: Every other Papanicolaou smear diagnosed during a 5-year period at our institution was reviewed. There were 1947 cases with dysplasia or carcinoma. Dysplasia was defined as a lesion of disordered squamous epithelial differentiation and was graded by standard criteria. The mean, median, and mode ages of the women were determined by diagnosis. Normal (symmetrical) distribution was tested for each population, and significant differences were sought by diagnosis. RESULTS: Normal distribution was rejected for the ages of women with all grades of dysplasia and carcinoma in situ, but not for the ages of women with carcinoma. CONCLUSIONS: Because the ages of women with dysplasia are not distributed normally, but are asymmetrically skewed to younger women, we suggest that the mode better describes the central tendency for ages of women with dysplasia. The difference between the mean and mode ages of these women explains the apparent discrepancy between the reported mean ages and our clinical impression. Appropriate descriptive statistics like these help the clinician evaluate individual patients in the true context of the disease. PMID- 8355948 TI - Thermal artifacts and inter-gynecologist variation of laser cone biopsies of the cervix. AB - OBJECTIVE: To evaluate the extent of thermal artifacts and the inter-gynecologist variation in CO2 laser cone biopsies for cervical intraepithelial neoplasia (CIN) using high power density. METHODS: All 1180 histologic sections from 93 CO2 laser cone biopsies performed by nine gynecologists were evaluated by morphometry. Power density of 19,700 W/cm2 and spot size of 0.43 mm were used. The lengths of different epithelia, the distance from CIN to the excision margins, the thermal artifacts, and the extension of denudation were analyzed. Mean values and standard deviations were analyzed for all indices. The inter-gynecologist variation was analyzed using one-way analysis of variance, Tukey-Kramer Honestly Significant Difference test, and chi 2 contingency table analysis regarding cones classified as "good" or "not good". RESULTS: The mean length of analyzed surface per cone was 134 mm. In 3% of the sections, the sum of artifacts at the external excision margin exceeded the average "minimum free distance" from CIN to the margin (2.88 mm). At the endocervical excision margin, the free distance was exceeded in 17% of the sections. Eighteen percent of the cones had CIN at the excision margins, with no significant differences between gynecologists (P = .83). Differences existed between gynecologists regarding free minimum distance and minor thermal artifacts at the external margin, but when clinically relevant groups were applied, no significant differences were found (P > .05). CONCLUSION: We found that a high power density at CO2 laser cone biopsy resulted in specimens with minimal thermal artifacts compared to other authors who used low power density. No clinically relevant differences were found between the gynecologists regarding free margins or artifacts. PMID- 8355949 TI - Management of patients with positive margins after cervical conization. AB - OBJECTIVE: To evaluate conservative management of patients undergoing cervical conization with cone margins positive for dysplasia. METHODS: The outcomes of 93 patients with cone biopsies that had margins positive for dysplasia were tabulated. RESULTS: Thirty of 47 patients (64%) undergoing conization only and followed by cytology had negative Papanicolaou smears for at least 2 years. Twenty-one of 37 women (57%) with conization and immediate hysterectomy had no residual disease in the cervix. Three of nine women (33%) with conization and delayed hysterectomy had no detectable dysplasia in the remaining cervix. There was no case of progression to invasive disease. The overall resolution rate was 58%. Persistence of disease was found most often at the endocervical margins associated with cervical intraepithelial neoplasia grade III. CONCLUSION: Patients with cone margins positive for dysplasia can be followed appropriately with cytology. In cases of recurrent abnormal Papanicolaou smears, colposcopy, biopsies, and endocervical curettage should be repeated. PMID- 8355950 TI - Cytologic examination of ovarian cyst fluid for the distinction between benign and malignant tumors. AB - OBJECTIVE: To assess the feasibility of using cytologic examination of ovarian cyst fluid for distinguishing between benign and malignant tumors. METHODS: Cyst fluid was aspirated at surgery in 83 women with benign and 35 women with malignant (25 invasive and ten borderline) ovarian tumors and submitted for routine cytologic examination. RESULTS: The specificity of the cytologic examination was 100%, but the sensitivity and negative predictive value were only 26 and 76%, respectively. CONCLUSION: The low sensitivity and negative predictive value of cytologic cyst fluid examination preclude its use for the distinction between benign and malignant ovarian tumors. PMID- 8355951 TI - Three-year results after neoadjuvant chemotherapy, radical surgery, and radiotherapy in locally advanced cervical carcinoma. AB - OBJECTIVE: To evaluate the complications and results of neoadjuvant treatment before surgery and radiotherapy in locally advanced cervical carcinoma. METHODS: Between March 1988 and June 1989, 24 consecutive patients with locally advanced cervical carcinoma received chemotherapy consisting of six weekly courses of cisplatin (50 mg/m2), vincristine (1 mg/m2), and bleomycin (30 mg), followed by radical hysterectomy and radiotherapy. Lymph node metastases were detected by means of lymphangiography and confirmed by fine-needle aspiration in 21 patients. RESULTS: Twenty-one women (87.5%) completed the planned sequence of treatment and 16 (66.7%) achieved objective responses. Three patients did not complete chemotherapy (one refusal, one myocardial infarction, one severe allergic reaction) and were treated further by radiotherapy. Nineteen subjects (79%) underwent subsequent radical surgery and radiotherapy without serious complications. After a minimal follow-up of 3 years, 16 patients had died of disease. Distant recurrences developed in only three of eight women in whom the nodes were negative originally, possibly reflecting systemic effectiveness of the chemotherapy. CONCLUSION: This sequence of treatment, although feasible, does not seem to improve long-term survival compared to standard treatment. PMID- 8355952 TI - The effect of lactation on glucose and lipid metabolism in women with recent gestational diabetes. AB - OBJECTIVE: To investigate the effect of lactation in the puerperium on glucose and lipid metabolism in women with recent gestational diabetes. METHODS: In women with recent gestational diabetes, we examined the effect of 4-12 weeks of lactation on glucose tolerance (2-hour oral glucose tolerance test) and on fasting serum lipids (total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and triglycerides). Of 809 women tested in the puerperium, 404 elected to breast-feed and 405 did not lactate. RESULTS: The mean (+/- standard deviation) maternal age (31.6 +/- 5.9 versus 30.5 +/- 6.3 years), body mass index (28.8 +/- 5.1 versus 28.8 +/- 4.5 kg/m2), and parity (3.0 +/- 1.6 versus 2.8 + 1.7) were not different between the lactating and nonlactating groups, respectively. Glucose metabolism improved in the lactating group, indicated by a significantly lower total area under the glucose tolerance curve (17.0 +/- 4.2 versus 17.9 +/- 5.0 g.minute/dL; P = .01), mean fasting serum glucose (93 +/- 13 versus 98 +/- 17 mg/dL; P = .0001), and mean 2-hour glucose level (124 +/- 41 versus 134 +/- 49 mg/dL; P < .01). These differences were significant after adjusting for maternal age, body mass index (BMI), and the use of insulin in pregnancy. Nursing had no effect on total cholesterol, LDL cholesterol, or triglyceride levels. However, the mean serum HDL cholesterol was elevated in the lactating group after adjusting for maternal age, BMI, and pregnancy insulin use compared with the nonlactating group (48 +/- 11 versus 44 +/- 10 mg/dL; P < .01). CONCLUSIONS: Lactation, even for a short duration, has a beneficial effect on glucose and lipid metabolism in women with gestational diabetes. Breast-feeding may offer a practical, low-cost intervention that helps reduce or delay the risk of subsequent diabetes in women with prior gestational diabetes. PMID- 8355954 TI - Determinants of utilization of Tay-Sachs screening. AB - OBJECTIVE: To identify the characteristics of patients associated with optimal utilization of Tay-Sachs screening. METHODS: Medical records of patients undergoing amniocentesis for genetic diagnosis were reviewed. Three hundred twenty-nine of 537 charts evaluated were from individuals at risk for Tay-Sachs heterozygosity. Among these, 213 couples had previously been screened for Tay Sachs. In 116 couples, neither member of the couple had been screened before amniocentesis. A concurrent reference group consisted of 208 couples without an indication for Tay-Sachs screening. Patient characteristics, including ethnicity, genetic screening history, parental ages, and pregnancy history, were reviewed for each group. Analysis of variance and likelihood chi 2 test were used for statistical analysis. RESULTS: There were no significant differences in maternal age or reproductive history among the groups. The most common indication for amniocentesis was advanced maternal age for all three groups. However, the previously screened group was more than twice as likely to self-refer because of a positive family history or patient anxiety than was the unscreened group (P = .006). Conversely, the unscreened group was more than twice as likely as screened couples to be referred because of a positive high or positive low maternal serum alpha-fetoprotein level (P = .002). CONCLUSION: Despite 2 decades of professional and lay education, many couples are unaware of their individual risk for Tay Sachs heterozygosity. Additional education, most likely at the professional level, is needed to maximize informed participation. PMID- 8355955 TI - Referees: their roles, rights, and responsibilities. PMID- 8355953 TI - Transfer of carbetocin into human breast milk. AB - OBJECTIVE: To study the transfer of carbetocin into human breast milk. METHODS: Five healthy nursing women, 7-14 weeks postpartum, emptied their breasts using a breast pump and then received 70 micrograms carbetocin by intramuscular injection. Using a radioimmunoassay, the concentrations of carbetocin were measured in plasma and breast milk samples obtained before carbetocin administration and at 15, 30, 60, 90, 120, and 240 minutes after drug administration. RESULTS: For plasma, the mean (+/- standard deviation) area under the curve (AUC) of carbetocin versus time was 1119.3 +/- 315.9 pg/mL, a value about 50 times higher than the mean AUC for carbetocin in breast milk (18.6 +/- 13.7 and 29.0 +/- 23.8 pg/mL for the right and left breast, respectively). The ratio of milk to plasma AUC was low: 1.7 +/- 0.9 and 3.1 +/- 2.8% for the left and right breast, respectively. No serious adverse reactions occurred and no clinically significant changes in vital signs were found. CONCLUSION: Very little carbetocin is transferred into human breast milk, presenting little risk to breast-fed infants. PMID- 8355956 TI - Is deception for reimbursement in obstetrics and gynecology justified? AB - Deceptive reporting to insurers of procedure indications to obtain reimbursement for non-covered services creates ethical and legal problems for practitioners. The motive for deceptive reporting is rooted in the expectation that any medical intervention recommended by the physician--even if of marginal benefit--should be covered. This traditional expectation collides with changing medical economics. Patient expectations of medical technology and insurance also promote deception. The deceptive physician fails to acknowledge a changed paradigm of medical economics, threatens his or her future practice, and does not model technical and ethical virtues to residents and students. Such deception preempts any possible dialogue with insurers that might result in coverage for a larger group of patients. The harmful outcomes of false reporting, present and future, far outweigh any temporary monetary gain for the patient or physician. PMID- 8355957 TI - Racial differences in oral glucose screening test results: establishing race specific criteria for abnormality in pregnancy. PMID- 8355958 TI - [Wilhelm His (the elder)]. PMID- 8355959 TI - [The crystalline lens as a model for studying the cellular and molecular mechanisms of differentiation in the adult organism]. AB - This review summarizes the published and authors own data about characteristics of expression of tissue-specific lens proteins (crystallins) during differentiation of lens epithelial cells into lens fibers in adult mammals, birds, reptiles, and amphibians. Information is analyzed about the presence, synthesis, and localization of different crystallins in lens epithelium and fiber cells of lens cortex and nucleus which correspond to sequential stages of lens cell differentiation. The data available suggest that morphologically similar differentiation of lens epithelial cells into fibers in different classes of vertebrates is accompanied by different programs for activation (and/or increase) of tissue-specific protein synthesis. PMID- 8355960 TI - [The DNA content of the neurons in the embryonic cerebellum transplanted into the cerebral cortex of adult rats]. AB - Cerebellum of rat embryos at day 17 of gestation was transplanted into sensomotor cortex of adult syngenic rats. DNA content in granule and Purkinje cells of the transplant was determined cytophotometrically on day 30 after surgery. It is shown that granule cells are diploid; about 3% Purkinje cells contain hyperdiploid and tetraploid nuclei which corresponds to the content of such cells in the adult cerebellum. The conclusion is drawn that cell hyperploidy does not depend on the functional load but is essential property of the tissue. PMID- 8355961 TI - [Bilateral symmetry of the dermatoglyphic characteristics in Down's syndrome]. AB - Dermatoglyphic traits were analyzed in 132 patients with Down syndrome. The level of bilateral symmetry of dermatoglyphic indices in these patients was found to be higher than in normal people (control). By this parameter, patients with Down syndrome showed lower intragroup variation than the control group. It is suggested that such difference is due to a more primitive developmental pathway. PMID- 8355962 TI - Intraocular pressure and mechanical ventilation. AB - Mechanical ventilation increases superior vena cava pressure and should theoretically increase episcleral venous pressure and intraocular pressure (IOP). A Keeler Pulsair Non Contact Tonometer was used to measure the IOP's of six subjects with no history of glaucoma or ocular hypertension. At 30 min of supine mechanical ventilation of tidal volume with low (7 to 15 cm H2O) peak inspiratory pressures, the IOP's were no different than at the end of a 30-min control period of supine spontaneous ventilation. However, using high (60 cm H2O) peak inspiratory pressures for 1 min after tidal volume ventilation, IOP's were 32.7% higher than at the end of the supine spontaneous ventilation control period (p < 0.05). Patients requiring long-term mechanical ventilation at high peak inspiratory pressures may be at increased risk of vision impairment secondary to machine-induced increase of IOP. PMID- 8355963 TI - Decreased uncorrected vision after a period of distance fixation with spectacle wear. AB - Myopes of low degree commonly report that their vision seems poorer upon removal of their spectacles compared to that after a period without spectacle wear. Notably, this difference in vision can be appreciated after distance fixation. In this paper, we propose and test several alternative hypotheses to explain the phenomenon: an accommodative response to spectacles, sensory adaptation, or altered criteria for blur of psychological origin. We measured visual acuity (VA), refractive error, and lens thickness on 10 subjects with less than 2.00 D of myopia. Testing was performed after two 90-min sessions viewing at distance. At one session, the subjects wore their current spectacle correction and, at the other session, no correction was worn. VA underwent a slight but significant decrease (0.4 of a line) after the session in which spectacles were worn, but no difference in refractive error or lens thickness was found. The change in acuity in the absence of a refractive shift suggests sensory adaptation to blur. However, the demonstrated change in VA appears to be less than that which is subjectively reported; accordingly, psychological input cannot be ruled out. PMID- 8355964 TI - Dark focus of accommodation and nervous system activity. AB - The purpose of this study was to evaluate the relation between physical exercise and dark focus of accommodation. Varsity intercollegiate runners (N = 12) participated in the experiment. Measurements of dark focus and pulse rates were taken before and after running 400 m. The hypothesis that arousal of the sympathetic nervous system through physical exercise would result in an inward shift of the dark focus was investigated. A repeated measures t-test was used to analyze the difference of dark focus between resting and running. These findings suggest that arousal of the sympathetic nervous system does have a significant effect on dark focus of accommodation. PMID- 8355965 TI - Measurement of elastic modulus of the bovine cornea by means of holographic interferometry. Part 1. Method and experiment. AB - Holographic interferometry of the cornea of fresh, enucleated bovine eyes placed in air was used for determination of the elastic modulus of the central part of the cornea. The high sensitivity of the method enables measurement of the radial distension of the cornea even for intraocular pressure (IOP) changes equal to 5 Pa (0.05 mbar or approximately 0.0375 mm Hg). The method of calculation of the tangent Young's modulus of the cornea Et, based on data obtained from double exposure as well as real-time holographic interferograms and on some geometrical data describing the form of the cornea are presented. The average value of Et amounting to 1.42.10(5) Pa was calculated from 2 interferograms of the same eye. PMID- 8355966 TI - Astigmatic optical systems with separated and prismatic or noncoaxial elements: system matrices and system vectors. AB - A general system of noncoaxial separated astigmatic optical elements is examined. Allowance is made for prismatic elements including decentered lenses and refracting surfaces, prisms, and plane interfaces. The directions and positions of a ray entering and emerging from the system are related by a system matrix and a system vector. Given an incident ray one can readily obtain the emergent ray. The analysis is of fundamental importance for visual optics. Two numerical examples are presented. One is a model eye with astigmatic and obliquely crossing astigmatic and decentered surfaces. PMID- 8355967 TI - Measurement of central and peripheral dynamic visual acuity thresholds during ocular pursuit of a moving target. AB - Previously, visual acuity thresholds for eccentric retinal points have been documented for targets that oscillate while the observer fixates a central point. This research describes the situation where the observer tracks a moving target in constant linear motion, thereby involving the pursuit and saccadic eye movements. The increase of visual acuity thresholds with target motion (0 to 70 degrees/s) was evaluated as a function of retinal eccentricity. Nine retinal points were evaluated, (central, 5 degrees and 10 degrees nasal, 5 degrees and 10 degrees temporal, 5 degrees and 10 degrees superior, and 5 degrees and 10 degrees inferior to the fovea). Eight normal subjects viewed computer-generated randomly oriented E's monocularly through a horizontally rotating mirror. A computer automatically calculated the minimal angle of resolution (MAR) threshold values. Result indicated that the change in visual acuity thresholds was dependent upon retinal location. The thresholds for central and peripheral eccentricities plotted as a function of angular velocity were linear but the slope of the linear function was much reduced for peripherally viewed targets compared to centrally viewed targets. Although both peripheral and central visual acuity thresholds may increase with increasing target velocity due to velocity mismatch errors and saccadic suppression and/or omission, the reduction in slope for peripherally viewed targets may be due to differential temporal summation, retinal smear, and/or separate retinogeniculate pathway processing. PMID- 8355968 TI - Subjective assessment of contact lens wear by army aircrew. AB - Because 23% of Army aviators are ametropic, contact lenses have drawn increased attention as a spectacle substitute to solve system compatibility problems. From November 1988 until October 1991, a series of contact lens research protocols were conducted to develop a comprehensive database on contact lens wear in varied environments. Questionnaires were used to assess suitability and acceptability of routine contact lens wear. Responses from 202 subjects were obtained from September 1989 through September 1991. The questions explored operational and safety of flight issues of contact lens wear. Subjects overwhelmingly approved of contact lens use in all settings: 95% expressed greater combat readiness and effectiveness with contact lenses, 98% felt contact lens use (and maintenance) in the cockpit had no adverse impact on safety of flight, and 98% endorsed the routine use of contact lenses. These data highlight Army aircrew acceptance of contact lens use. PMID- 8355969 TI - Potential applications of ocular thermography. AB - Thermography is an investigative technique which allows rapid color-coded display of the temperature across a wide surface by means of infrared detection. We describe an ocular thermographic study of a normal population and present case studies describing the application of this technique for patients with ocular disease. We found that 95% of the normal population have an interocular temperature difference (temperature of center of right cornea minus temperature of center of left cornea) of 0.60 degrees or less. There appears to be a greater difference in temperature between the limbus and the center of the cornea in patients with dry eyes. This technique has potential for evaluating tear film disorders and inflammatory conditions, for monitoring the progress of such conditions, and for evaluating the efficacy of various treatments. PMID- 8355970 TI - Humidity-conditioned gravimetric method to measure the water content of hydrogel contact lens materials. AB - A method to determine the humidity-conditioned gravimetric water content of hydrogel contact lens materials has been developed, in which errors due to blotting have been eliminated by conditioning the lens in a series of relative humidity (RH) environments before measuring the water content gravimetrically, and then extrapolating the water content to 100% RH. This method has been used to determine the water contents of representative materials from each of the four FDA lens groups, which were compared with their labeled values, as well as with values obtained from refractive index measurements. The deviation of the water content of soft contact lenses as measured by refractive index from that obtained gravimetrically increased as the water content decreased. The humidity conditioned gravimetric method to determine water content of hydrophilic contact lenses is being proposed as an International Organization for Standardization (ISO) standard, as an improvement over the gravimetric and refractive index methods. PMID- 8355971 TI - Redefining the optometric examination: addressing the vision needs of older adults. AB - The aging of America's population will result in an increased number of older adult patients in optometric practices. Although older patients frequently report declines in their vision, the results of high contrast testing procedures often do not correlate with the symptoms. Age-related functional vision decrements can impact upon an individual's ability to perform the activities of daily living. I explored the relation between reported visual complaints and the results of objective tests for older adults (N = 50) as compared with middle-aged adults (N = 20). Decrements in visual acuity, contrast sensitivity, glare sensitivity, color vision, and stereopsis were apparent in the older group and all were significant at alpha = 0.05. Open-ended questions elicited more visual complaints from older adults than from middle-aged adults. However, only the reported complaint of decreased vision was related to visual decrements as determined by clinical testing (chi 2; p = 0.0596). These results indicate that task-specific case history questions may provide greater insight into older adults' visual performance in their normal environment. Additional testing in the areas of contrast sensitivity, glare sensitivity, stereopsis, and color vision should also be included in the optometric examination when warranted. PMID- 8355972 TI - Optometry research. Part 3: Faculty publications. AB - I compared the production of faculty-produced publications among the U.S. schools and colleges of optometry and the Department of Veterans Affairs (VA) Optometry Service. These publication rates were viewed against the schools' rankings in National Eye Institute (NEI) funding (see Part 2), student/faculty ratios, faculty salaries, and the presence of a graduate degree program. The schools and the VA grouped into three levels of publication production with five of first rank, four of middle rank, and eight of lower rank. The five leading producers in the period 1982 through 1991 were Berkeley, Alabama, Houston, VA, and State University of New York (SUNY). Since 1982 VA optometrists have authored the largest number of articles published in the Journal of the American Optometric Association and since 1985 have been the leading group of continuing education (CE) lecturers at the Academy. PMID- 8355973 TI - Optometry in the lead: public education and ultraviolet radiation. PMID- 8355974 TI - Aniseikonia with intraocular lenses. PMID- 8355975 TI - [Adjuvant BCG immunotherapy in the management of superficial bladder tumors]. AB - The net benefit of BCG immunotherapeutic prophylactic effect on recurrence of superficial bladder tumours was investigated. The BCG treatment group consisted of 121 stage Ta, T1 patients, while the control group, 49 patients, was treated only with transurethral resection. During 3-year follow-up recurrence rate in the control group was 55.1%, while in the BCG group in the two-and-a-half-year follow up it was 23.9%. The yearly repeated 6-week cycles resulted in decrease of recurrence rate to 11.8%. The recurrence indexes were 2.2 and 0.6 in the control group and in the repeated treatment group respectively. A progression rate of 18.8% was recorded in the control group and 4.1% in the treatment group. Finally both clinical and investigative results were summarised and the necessity of repeated immunotherapeutic BCG courses were emphasized. PMID- 8355976 TI - [Pen-type insulin dispenser for intensive insulin therapy]. AB - The authors investigate the advantage of the intensified insulin therapy and the use of pen-type devices in the practice of the Diabetic Outpatient Clinic of National Institute of Cardiology. The metabolic control improved markedly during intensified insulin therapy already after a short time as three months without any change in the applied dosage. Furthermore pen-type devices have been recognized to let the patients better accept the daily more than two injections, to improve the life-style, and last but not least to decrease the waste quantity of insulin. Authors want to draw attention to the fact that more than 33% of diabetic patients with intensified insulin therapy have a higher demand for insulin, then it could be injected by the pen devices used at this time and by cartridges available in Hungary at this moment. Therefore, availabilities of both cartridges of 3 ml volume would become necessary without any delay. PMID- 8355977 TI - [Repair of an electrode breakage in a permanent pacemaker by internal bypassing]. AB - A possible complication of the definitive pacemaker therapy is the fracture on the electrode which usually needs new electrode replacement. A new method is discussed as the electrical fault caused by fracture is resolved by internally bypassing the broken part of the electrode with a guide-wire. This method is more simple and economical and quicker than the electrode replacement and provides more safety for the patients. This method is therefore recommended to be spread. PMID- 8355978 TI - [Fatal myocardial lesion in systemic lupus erythematosus]. AB - The authors present the case of a 47-year old female patient. She suffered from a moderate activity SLE for two years. The outcome of SLE was changed by an ulcer because of leg injury, which was repeatedly infected. Severe polyarthritis, leucopenia, thrombocytopenia, clinical signs of vasculitis and in the last two months fever, high ESR, and pericarditis appeared. The angina pectoris, the cardiac decompensation, the electrocardiogram, the echocardiogram was suspect to diffuse myocardial lesion. Cardiac decompensation caused the death of the patient. Besides the activation of her autoimmune disease, infection was suspect in the patient taken immunosuppressive and steroid drugs, though it could not be verified. Autopsy verified besides the recent necrosis of heart without reaction, and multifocal myocardial abscess, which appeared possible in the terminal phase. PMID- 8355979 TI - [Remembering Mor Kaposi at Kaposvar]. PMID- 8355980 TI - [W. Griesinger and the "Thubingen Triad"]. PMID- 8355981 TI - [Successful treatment of hemorrhaging necrotizing pancreatitis with peritoneal dialysis]. PMID- 8355982 TI - Characterization and physical mapping of the genome of bacteriophage phi Aa from Actinobacillus actinomycetemcomitans. AB - The size, configuration and restriction map of Actinobacillus actinomycetemcomitans bacteriophage phi Aa DNA was determined by means of restriction endonuclease analysis. Digestion of the phi Aa DNA with restriction enzymes Hind III, Eco RI and Sal I produced 6, 5, and 4 fragments, respectively. Based upon the sum of the sizes of the restriction fragments of these enzymes, the DNA was estimated to be 47.2 kilobase pairs in length. A restriction map was constructed using Hind III and Sal I. Incubation with exonuclease Bal 31 for increasing lengths of time resulted in progressive hydrolysis of the DNA, as expected for a linear molecule. No sub-molar fragments or diffuse bands were observed in the agarose gels of the restriction endonuclease digests of the phi Aa DNA. Attempts at ligating the ends of the DNA were consistently unsuccessful. Therefore, we found no evidence for cohesive ends, a circular permutation of the genome or for headful packaging mechanism from a concatameric DNA precursor. PMID- 8355983 TI - Identification of Actinobacillus actinomycetemcomitans: polymerase chain reaction amplification of lktA-specific sequences. AB - Actinobacillus actinomycetemcomitans has been strongly implicated in the etiology of localized juvenile periodontitis. Techniques used in the identification of this periodontal pathogen include cultural, biochemical, immunological and DNA hybridization analysis. In this study, we report the use of polymerase chain reaction (PCR) to amplify unique sequences of A. actinomycetemcomitans. Specific oligonucleotide primers LKT2 and LKT3 were designed to hybridize to the A. actinomycetemcomitans lktA gene, which encodes leukotoxin, a putative A. actinomycetemcomitans virulence factor. The LKT2 and LKT3 primers amplified lktA specific sequences from all 12 A. actinomycetemcomitans strains tested. In another set of experiments, 13 other bacterial species, most of which are normal residents of the oral cavity, were tested with these primers. These PCR amplifications also contained 2 additional primers, RRN4 and RRN5, which served as positive controls; RRN4 and RRN5 were designed to amplify specific sequences of eubacterial 16S ribosomal DNA (rDNA). PCR amplifications of all bacterial species tested, including A. actinomycetemcomitans, yielded 16S rDNA-specific DNA fragments. Furthermore, each bacterial species tested, with the exception of A. actinomycetemcomitans, failed to amplify lktA sequences. The LKT and RRN primers were used in further PCR experiments to detect A. actinomycetemcomitans directly from gingival fluid samples. The results clearly demonstrate the simplicity, rapidity, specificity and accuracy of the LKT primers in the identification of A. actinomycetemcomitans. PMID- 8355984 TI - Seroclassification of hitherto nontypeable Actinobacillus actinomycetemcomitans strains: evidence for a new serotype e. AB - Serotyping of 89 Actinobacillus actinomycetemcomitans isolates by indirect immunofluorescence with serotype-specific monoclonal antibodies yielded 10 nontypeable strains. The aim of the present study was to re-evaluate the seroclassification of these strains with a different assay. Electroblotted antigens of nontypeable isolates and selected reference strains were immunostained with 37 human sera containing high antibody titers to A. actinomycetemcomitans. Such immunoblots typically showed an immunodominant, serotype-specific antigen smear. Twelve human sera were found to recognize specifically serotype a, 10 serotype b and 9 serotype c. Three sera contained antibodies to 2 or all 3 serotype antigens; 3 sera had no activity to any reference strain smear antigen. There was complete agreement between the seroclassification of the reference strains with the monoclonal and the polyclonal reagents. Seven of the 10 strains, nontypeable with monoclonal antibodies, could also not be typed by the human sera. Of the remaining 3 strains, one belonged to a previously unrecognized serovar of serotype a, and 2 isolates expressed a novel smear antigen detected by the 3 human sera containing no antibodies to the serotype a, b, or c antigens. We propose that these 2 strains be assigned to a new A. actinomycetemcomitans serotype, designated serotype e. PMID- 8355985 TI - Effect of outer membrane of Treponema denticola on bone resorption. AB - The effect of the outer membrane (outer sheath) of Treponema denticola on bone resorption was studied. Bone resorption was measured by the release of previously incorporated 45Ca from the shafts of the radii and ulnae of 19-day fetal rats. A treated-over-control ratio (T/C ratio) significantly greater than 1 indicated the stimulation of bone resorption by the test substance. The addition of outer membrane of T. denticola increased the release of 45Ca from the assay bones. The minimum concentrations required to yield significant 45Ca release from the assay bones were 15, 22 and 75 micrograms protein/ml for serovars a, b and c, respectively. These protein values corresponded to estimated lipopolysaccharide contents of 0.6, 0.8 and 2.8 micrograms/ml, based on 3-deoxy-2-manno-octulosonate analysis. Heat treatment of outer membrane (60 degrees for 30 min) did not change the effect on 45Ca release. Parathyroid hormone or prostaglandin E2, known to act synergistically with lipopolysaccharides in bone resorption, was also added to the assay system. Neither prostaglandin E2 at 10(-7) M nor parathyroid hormone at 40 ng/ml, by itself, increased 45Ca release. However, in the presence of 10 micrograms protein/ml of outer membrane of serovar b at 120 h, the T/C ratio was increased to 1.31 +/- 0.07 and 1.58 +/- 0.118, respectively. These results suggest that a lipopolysaccharide-like material is present in the outer membrane of T. denticola that may be responsible for bone resorption in the in vitro system. PMID- 8355986 TI - Salivary effects on polymorphonuclear leukocyte functions. AB - Respiratory burst, enzymatic degranulation and bacterial killing were investigated on peripheral blood polymorphonuclear leukocytes (polymorphonuclear leukocytes) incubated with a pool of salivary fluids elicited from healthy donors. Low saliva concentrations primed polymorphonuclear leukocytes for enhancement of O2 consumption, O2- and beta-glucuronidase release and Staphylococcus aureus killing. Whole saliva, on the contrary, depressed all tested phagocytic activities. PMID- 8355987 TI - Bacteria reactive to plaque-toxin-neutralizing monoclonal antibodies are related to the severity of gingivitis at the sampled site. AB - Certain monoclonal antibodies (Mabs) neutralize the inhibition of HL60 cell growth by bacterial plaque extracts. The aim of this study was to enumerate and identify the bacteria reactive to these Mabs at sites where periodontal disease was measured by gingival index, pocket depth and attachment loss. The bacterial colonies were grown on blood agar and the colonies counted directly and after immunoblotting. Sites that bled on probing (n = 15) had a mean of 3.35% Mab positive colonies (SEM = 0.52%) and sites that did not bleed (n = 9) had a mean of 1.61% (SEM = 0.41%). The percentage of Mab-positive colonies also correlated with gingival index but not with the total number of colonies sampled, attachment loss or pocket depth. Antigen was expressed by 4 genera: strains of Streptococcus sanguis and/or Eikenella corrodens (8 sites), Staphylococcus epidermidis (4 sites) and Corynebacterium minutissimus (1 site). The results suggest that the antigens detected on these bacteria by the Mabs may be processed to form toxins and maintain gingivitis by irritating the surrounding cells. PMID- 8355988 TI - Changes in the prevalence of subgingival enteric rods, staphylococci and yeasts after treatment with penicillin and erythromycin. AB - The changes in the balance of microbial flora in the periodontium after antibiotic treatment were investigated in a blind study. The prevalence of gram negative enteric rods, staphylococci and yeasts was followed before and during penicillin or erythromycin treatment of 72 periodontitis patients without periodontal cleaning. The prevalence of subgingival coagulase-positive staphylococci increased significantly following systemic penicillin therapy. After systemic erythromycin therapy, the prevalence of subgingival gram-negative enteric rods increased. Ten of 24 (42%) patients receiving systemic penicillin therapy developed clinical evidence of periodontal abscesses. In the absence of conventional mechanical cleaning, systemic administration of penicillin and erythromycin antibiotic to patients with pre-existing periodontitis may lead to periodontal superinfection with opportunistic organisms. PMID- 8355989 TI - A successful method for quantifying viable oral anaerobic spirochetes. AB - Spirochetes are markedly prevalent in periodontal disease but are not included as predominant cultivable organisms because of the inability to quantify them by viable count. A successful method was developed for enumerating viable oral spirochetes as colony-forming units (CFU) in an agarose-based medium. Treponema denticola, Treponema vincentii and Treponema socranskii in log-phase growth in new oral spirochete (NOS) broth were used for evaluation of the method. Critical components of the method include enzyme-free low temperature-gelling (37 degrees C) agarose in NOS medium in small tissue-culture flasks into which the spirochetes were seeded and diluted. The flasks were anaerobically incubated in a glove-box. Reliable, consistent and reproducible viable counts of pure spirochete cultures were obtained. The injurious effects of spirochete temperature sensitivity were averted by using molten agarose at 37 degrees C. Distinctive colony morphologies of spirochete species could be compared from pure cultures. Addition of rifampin into the medium showed no decrease in spirochete CFU count. The method as described allows for selection of mutants and detection of biochemical activity and is potentially useful for enumeration of spirochetes from periodontal pockets as members of the predominant cultivable flora. PMID- 8355990 TI - Attachment of Treponema denticola strains to monolayers of epithelial cells of different origin. AB - The attachment of 10 different Treponema denticola strains to monolayers of 4 types of epithelial cells derived from rat palatal epithelium, guinea pig ear, human buccal epithelium and human corneal epithelium was screened microscopically. Most T. denticola strains were able to attach to all four types of epithelial cells. The T. denticola strains seemed to attach better to epithelial cells derived from primary cultured material. The T. denticola strains showed different degrees of attachment. Scanning electron microscopy studies revealed that the attachment of T. denticola was not only tip-associated but occurred also at random points in close contact with microvilli of the epithelial cells. Attached spirochetes were non-uniformly distributed over the monolayers, indicating the presence of receptive subpopulations of epithelial cells in the monolayers. PMID- 8355991 TI - Identification of plasmids in Actinobacillus actinomycetemcomitans and construction of intergeneric shuttle plasmids. AB - A collection of 39 isolates of Actinobacillus actinomycetemcomitans, obtained from laboratories located in 5 different geographical regions of the United States, was examined for the presence of plasmid DNA. Only 2 of the strains examined, designated VT736 and VT745, harbored detectable plasmids. Strain VT736 contained a 1.9 kb plasmid species (pVT736-1) and a larger ( > 30 kb) species (pVT736-2). Both plasmids were detected in the covalently closed circular DNA fraction of dye buoyant density gradients. However, only the smaller plasmid was observed in agarose gels containing plasmid-enriched cell lysates prepared by a rapid screening procedure. Strain VT745 contained a single, 24 kb, plasmid (pVT745) that was observed consistently in plasmid-enriched lysates, as well as in the plasmid band of dye buoyant density gradients. A restriction endonuclease map of pVT736-1 was constructed. The plasmid contained one site each for the enzymes HincII, KpnI and XhoI, located 600 to 700 bp from each other on the pVT736-1 map. HincII-digested pVT736-1 DNA could not be cloned in Escherichia coli. However, intact pVT736-1 digested with KpnI or XhoI could be cloned in E. coli on pUC19 or pGEM7Zf(-), respectively. KpnI-digested pVT736-1 was cloned in both orientations on pUC19, but XhoI-digested pVT736-1 was clonable in only one orientation on pGEM7Zf(-). Each of the 3 types of chimeric plasmid constructs provided a potential A. actinomycetemcomitans/E. coli shuttle plasmid for the development of a genetic transfer system in A. actinomycetemcomitans. PMID- 8355992 TI - The methionine synthesis cycle and salvage of methyltetrahydrofolate from host red cells in the malaria parasite (Plasmodium falciparum). AB - Plasmodium falciparum, P. knowlesi and P. chabaudi showed a significant activity of methylenetetrahydrofolate reductase (MTHFR). The presence of this enzyme completes the methionine synthesis cycle, in which the one-carbon fragment from serine side-chain can be transferred to methionine. However, while metabolic labelling of methionine from L-3 [14C]serine could not be demonstrated in P. falciparum, the significance of MTHFR was implicated by a novel pathway for salvage of exogenous 5-methyltetrahydrofolate from the host cell. The methyl group of the cofactor was incorporated into methionine, and the folate cofactor was found in the same pool as that derived from de novo synthesis with p aminobenzoic acid as the precursor, shown previously as polyglutamylated 5 methyltetrahydrofolate. It is proposed from these results that the function of MTHFR and the methionine synthesis cycle is not the supply of methionine, but the generation of active folate cofactors from more stable precursors salvaged by the parasites. PMID- 8355993 TI - Rapid changes in the surface of parasitic nematodes during transition from pre- to post-parasitic forms. AB - All mammalian-parasitic stages of a range of nematode species investigated (Brugia pahangi, Acanthocheilonema viteae, Strongyloides ratti, Nippostrongylus brasiliensis, Trichinella spiralis and Ostertagia ostertagi) labelled in a surface-restricted manner with the fluorescent lipid analogues 5-N (octadecanoyl)aminofluorescein (AF18) or nitrobenzoxadiazole-cholesterol (NBD chol), but failed to bind other similar probes. In contrast, the surfaces of the 'pre-parasitic' infective stages of these species had affinity for neither AF18 nor NBD-chol. This exclusion of lipid analogues changed rapidly upon exposure of the larvae to tissue culture conditions which mimic the mammalian tissue environment (e.g. RPMI 1640/37 degrees C) such that the above probes could then insert into the surface layer of the larvae. The dauer larva of Caenorhabditis elegans also excluded the probes, but became permissive to labelling upon stimulation to emerge from the dauer state. The time taken for the surface transformation to occur ranged from less than 10 min in the vector-borne parasites to approximately 5 h in those which enter by the oral route, with direct skin-penetrators occupying an intermediate position. In all cases, the alteration proceeded too rapidly for it to have been associated with a moult. Fluorescence Recovery After Photobleaching (FRAP) studies of A. viteae larvae showed that approximately 50% of the AF18 probe was free to diffuse within the plane of the surface immediately after transformation. This is only a transitory state because AF18 was found to be highly restricted in its lateral diffusion on the surface of adult parasites. In the larvae of S. ratti, the change in affinity for AF18 was accompanied by the rapid shedding of an otherwise stable surface coat of polyanionic material, here visualized by labelling with fluorescein conjugated cationized ferritin. Incubation of larvae in lipid-rich host serum during the induction of transformation inhibited subsequent labelling with AF18. This possibly reflects competition for insertion sites and an in vivo propensity towards the acquisition of host lipid by invading parasites. PMID- 8355994 TI - Frequency of cross-fertilization in the human malaria parasite Plasmodium falciparum. AB - Two clones of the human malaria parasite Plasmodium falciparum, denoted 3D7 and HB3, were grown in vitro under conditions permitting the development of gametocytes. The two clones differ in their allelic forms of two antigen genes MSP1 and MSP2. The alleles can be distinguished as size differences of polymerase chain reaction (PCR) amplified fragments of repetitive regions of each gene. Mosquitoes (Anopheles stephensi) were fed on a mixture of these gametocytes. A total of 128 oocysts was isolated from the midguts of infected mosquitoes from 9 crossing experiments between the clones. DNA extracted from these oocysts was amplified by PCR. Oocysts which contained both alleles of each gene (MSP1 and MSP2) had developed from heterozygotes produced by cross-fertilization events between 3D7 and HB3 gametes. The remaining oocysts contained single alleles of each gene, in parent clone combinations, and these had developed from homozygotes formed by self-fertilizations. The results suggest that gametes in the original mixture fed to mosquitoes had undergone random mating. PMID- 8355995 TI - Modelling toxoplasma incidence from longitudinal seroprevalence in Stockholm, Sweden. AB - Age-stratified data on toxoplasma seroprevalence in pregnant women in Stockholm, Sweden for the years 1969, 1979 and 1987 provide the basis for an analysis of temporal patterns of Toxoplasma gondii infection, and estimation of the risk of maternal toxoplasmosis, in this population. A catalytic infection model, in which the rate or force of infection is assumed to be a function of time (and not, as is more usual, age), was employed to describe the observed changes in levels of toxoplasma seropositivity. A range of simple incidence functions (up to 3 parameters) were fitted using a method of maximum likelihood. The data were significantly better described by a linear or an exponential decay in the rate of infection through time compared with a constant level. More complex incidence functions gave no better data description. Thus, whilst there is strong evidence for declining incidence in Stockholm over the past 4-5 decades, the data do not allow discrimination between different possibilities for the nature of this decline. Based on these modelling results, best estimates of the force of infection in 1987 acting on susceptible women are within the range 0 to 0.0045/susceptible/year (95% confidence limits), yielding a possible risk of maternal toxoplasmosis of between 0 and 2.7 cases/1000 pregnancies. These values are shown to be significantly lower than estimates based upon an assumption of temporal stability in toxoplasma incidence, which may be of practical significance to public health policy. PMID- 8355996 TI - The influence of host blood on infection rates in Glossina morsitans sspp. infected with Trypanosoma congolense, T. brucei and T. simiae. AB - Trypanosoma congolense, T. brucei and T. simiae isolated from wild-caught Glossina pallidipes were fed to laboratory-reared G. morsitans centralis and G.m. morsitans to determine the effect of host blood at the time of the infective feed on infection rates. Bloodstream forms of trypanosomes were membrane-fed to flies either neat, or mixed with blood from cows, goats, pigs, buffalo, eland, waterbuck and oryx. The use of different bloods for the infective feed resulted in differences in infection rates that were repeatable for both tsetse subspecies and most parasite stocks. Goat, and to a lesser extent, pig blood facilitated infection, producing high infection rates at low parasitaemias. Blood from cows and the wildlife species produced low infection rates, with eland blood producing the lowest. Addition of D(+)-glucosamine (an inhibitor of tsetse midgut lectin) increased infection rates in most cases. These results indicate the presence of species-specific factors in blood that affect trypanosome survival in tsetse. In certain hosts, factors actually appear to promote infection. The nature of these factors and how they might interact with midgut lectins and proteases are discussed. PMID- 8355997 TI - Endotoxins and the pathogenesis of Trypanosoma brucei brucei infection in mice. AB - The involvement of endotoxins in Trypanosoma brucei brucei infection in CD-1 mice was investigated by the Limulus amoebocyte lysate (LAL) test. At 7 days post infection mean serum endotoxin level was elevated by 2.5 times (36.4 pg/ml cf. control 14.25 pg/ml, P < 0.001) and a similar increase was maintained throughout the infection (survival 28-35 days). Purified disrupted parasites contained significant endotoxin activity (mean value 280 pg/mg protein). The mouse infections were also associated with progressive Gram-negative bacteraemia (present in 4 out of 5 infected animals by day 28 p.i.). The increased endotoxin levels may be due to parasite products, the products of intercurrent bacterial infections, other unidentified sources (e.g. from the gut), or a combination of these. It is concluded that the raised endotoxins may be important contributive factors in the pathogenesis of experimental murine trypanosomiasis. PMID- 8355998 TI - Characterization of Megatrypanum trypanosomes from European Cervidae. AB - Megatrypanum trypanosomes have been isolated from a number of different European Cervidae, but on the basis of morphology it has not been possible to define the species to which these isolates belong. We isolated Trypanosoma (Megatrypanum) theileri from 10 cattle, and Megatrypanum trypanosomes from 11 fallow deer (Cervus dama), 9 red deer (Cervus elaphus), and 4 roe deer (Capreolus capreolus) by blood culture on a biphasic medium (NNN agar slopes). Trypanosomes were propagated in Schneider's Drosophila medium and characterized by isoenzyme analysis and molecular karyotyping. Isocitrate dehydrogenase and phosphoglucomutase were visualized after starch gel electrophoresis of trypanosome lysates. By cluster analysis of this data all isolates from deer were clearly separated from the T.(M.) theileri isolates from cattle. Isolates from roe deer were different not only from T. (M.) theileri but also from the other deer isolates. Isolates from fallow deer and red deer were grouped together. Thus, there are probably at least two different species of Megatrypanum trypanosomes in the three Cervidae. One parasitizing roe deer, the other, apparently less host specific species, infecting red deer and fallow deer. Separation of the chromosomes of Megatrypanum trypanosomes by pulsed-field gradient gel electrophoresis (PFGE) showed that each isolate contained a large number (> 18) of chromosomes ranging in size from 300 to > 2200 kb. The molecular karyotypes were similar for all isolates, although no isolate was identical to another. PMID- 8355999 TI - A quantitative study of the susceptibility of cockroach species to Moniliformis moniliformis (Acanthocephala). AB - We exposed 19 species of cockroaches to Moniliformis moniliformis by administering shelled acanthors orally and by injecting hatched acanthors directly into the body cavity. The exposure method had little influence on susceptibility: with one exception, species that were susceptible to oral exposure were also susceptible to injected acanthors and, in no case, did acanthors develop in injected animals when they did not develop in orally exposed conspecifics. We found no support for the hypothesis that the intestine may be a barrier to M. moniliformis establishment in cockroaches. There is, however, clear interspecific variation in susceptibility to M. moniliformis infection. PMID- 8356000 TI - Dipstick dot ELISA for the detection of Taenia coproantigens in humans. AB - A dipstick dot ELISA for detection of Taenia-specific coproantigens was developed. The test was based on a sandwich ELISA using antibodies raised against adult Taenia solium. Antibodies were absorbed to nitrocellulose paper previously adhered to acetate plastic to form dipsticks. Once blocked with 5% skimmed milk and dried the antibody-coated dipsticks were stable for several weeks at room temperature. Both micro and dot ELISA formats were genus specific although the dot ELISA was less sensitive than the micro ELISA based on the same antiserum. During field studies, in which the majority of samples were tested in rural villages soon after collection, 3728 samples were tested. All samples were also examined by microscopy using formol ether concentration and individuals questioned to determine whether they were aware of being infected. After the initial diagnostic work individuals were treated with taeniacidal drugs for worm recovery. Use of the coproantigen test significantly increased the number of cases diagnosed. Of the 41 cases diagnosed by the three diagnostic techniques combined 31 were detected by the dipstick assay making it the most sensitive technique employed. The specificity of the dipstick assay was 99.9% with a positive predictive value of 88.6%. The combined diagnostic approach did not, however, diagnose all cases. The coproantigen test was fast and easy to use. Further improvements may make the dipstick test suitable for wide-scale use in field studies and diagnostic laboratories. PMID- 8356001 TI - Experimental onchocerciasis in chimpanzees: cellular responses and antigen recognition after immunization and challenge with Onchocerca volvulus infective third-stage larvae. AB - Immunization of chimpanzees with radiation-attenuated infective 3rd-stage larvae (L3) of Onchocerca volvulus did not induce strong protective immunity against a subsequent challenge infection; only 1 out of 4 immunized animals remained non patent (i.e. microfilariae-negative) after challenge, and may have been protected. However, during immunization and before challenge, a broad range of adult O. volvulus-derived antigens (OvAg) and also uterus-derived OvAg were recognized by circulating antibodies; moreover, the repertory of antigens recognized increased further in subsequently patent animals after challenge, particularly in the range of M(r) 12-42 kDa. In the immunized and non-patent chimpanzee, by contrast, serological recognition of uterus-derived OvAg with M(r) 14 kDa and 105 kDa disappeared by 19 months post-challenge (p.c.). During immunization, Acanthocheilonema viteae L3 antigens of M(r) 11-12 kDa were strongly recognized only by the non-patent animal, suggesting that recognition of these antigens may have supported resistance to the subsequent challenge infection. In immunized chimpanzees, a substantial increase in the cellular reactivity to OvAg was induced; this, however, declined by 19 months p.c. to levels similar to those seen prior to immunization. At that time, 3 out of 4 immunized animals were patently infected. The effect of exogenous cytokines on in vitro-reactivity of PBMC to OvAg was examined. Addition of exogenous IL-2 alone, IFN-gamma alone, and IFN-gamma in combination with IL-2, did not augment net cellular responses to OvAg by PBMC from infected and control chimpanzees. In the presence of IL-4 alone, IL-6 alone, IL-2 with IL-4, IL-2 with IL-4 and IFN-gamma, or IL-2 with IL-4 and IL-6, the net cellular reactivity to OvAg increased significantly in patent chimpanzees and reached levels similar to non-patent animals. Thus, non-patent chimpanzees maintain high cellular reactivity to OvAg and in vitro cellular unresponsiveness to OvAg on the part of patent chimpanzees is reversible after addition of several cytokines which act individually or synergistically. PMID- 8356003 TI - Centrocytic lymphoma: a distinct clinicopathologic, immunophenotypic, and genotypic entity. PMID- 8356002 TI - Estimation of intestinal nematode prevalence: influence of parasite mating patterns. AB - Prevalence of infection with intestinal helminths is usually assessed through stool examination. There are limitations in using this technique to measure infection status, since some infected individuals have no patent infection. The relationship between infection assessed by stool examination and actual infection prevalence is investigated for the three major nematode species--Ascaris lumbricoides, Trichuris trichiura and the hookworms--using a model which describes the presence of non-egg producing worm combinations. The analysis demonstrates that stool examination under-estimates the actual infection prevalence, and that the degree of under-estimation is dependent on the level of infection, the nematode species and the parasite sex ratio. These findings have implications for the validity of epidemiological surveys and the evaluation of control programmes. PMID- 8356004 TI - Limited forms of Churg-Strauss syndrome. PMID- 8356005 TI - Metastatic malignant neoplasms and secondary lymphomatous involvement of the breast: a study of 43 cases. PMID- 8356006 TI - Sources of variability in classifying common ovarian cancers using the World Health Organization classification. Application of the pathtracking method. PMID- 8356007 TI - Cervical adenocarcinoma and related lesions. Cytodiagnostic criteria and pitfalls. PMID- 8356008 TI - Neuroendocrine tumors of the nasal cavity. PMID- 8356009 TI - Targeting zinc protoporphyrin liposomes to the spleen using reticuloendothelial blockade with blank liposomes. AB - Metalloporphyrin inhibitors of heme oxygenase have been studied for use in the prevention of hyperbilirubinemia of the neonate. One report has suggested that incorporation of these drugs into liposomes can increase their localization to the spleen, dramatically reducing heme oxygenase activity in that important heme degrading organ. We sought to further increase porphyrin delivery to the spleen by using reticuloendothelial blockade with blank liposomes 2 h before injection of 0.3 microns extruded zinc protoporphyrin liposomes (L-ZnPP). Control adult rats without hemolysis had splenic heme oxygenase activity of 1.07 +/- 0.09 nmol carbon monoxide (CO)/h/mg protein. Rats treated with L-ZnPP alone had splenic heme oxygenase activity of 0.53 +/- 0.16 nmol CO/h/mg protein 6 h after L-ZnPP dosing. However, rats treated with 1000 mumol of blank liposomes per kg to saturate the reticuloendothelial system 2 h before L-ZnPP administration had splenic heme oxygenase activity of 0.25 +/- 0.16 nmol CO/h/mg protein at t = 6 h, which is significantly less than that of the L-ZnPP alone group (p < 0.05). In adult rats treated with heat-damaged red blood cells (RBC) to simulate hemolysis, treatment with 10 mumol of aqueous ZnPP per kg or 10 mumol of untargeted L-ZnPP per kg did not produce a difference from control in total body bilirubin production as estimated by CO excretion. However, RBC-treated rats given 1000 mumol of blank liposomes per kg 2 h before L-ZnPP administration produced significantly less CO than control, aqueous ZnPP-treated, and untargeted L-ZnPP treated rats from 8 to 12 h after RBC treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356010 TI - Molecular and genetic analyses of two patients with Pearson's marrow-pancreas syndrome. AB - Pearson's syndrome, a rare and fatal disorder characterized by refractory sideroblastic anemia and pancreatic insufficiency in infancy, is classified into mitochondrial cytopathies. To understand the molecular and genetic bases of this disorder, we have investigated the mitochondrial respiratory chain enzymes and the mitochondrial DNA (mtDNA) in two Japanese patients with Pearson's syndrome. Immunoblot analysis from various tissues showed the different grades of defects in the subunits of respiratory enzyme complexes. The analyses of mtDNA showed that the deletion in patient 1 spanned 4977 bp from the ATPase 8 gene to the NADH dehydrogenase 5 gene between 13-bp direct repeats, whereas the deletion in patient 2 spanned 3151 bp from the transfer RNA(His) gene to the cytochrome b gene unrelated to any repeated sequences. The deleted mtDNA was heteroplasmic in all the analyzed tissues, but the proportions of deleted mtDNA were quite different. We observed a tendency for the tissue with low percentages of normal sized mtDNA to show low contents of complex I subunits. Analysis of the entire sequence of both patient's mtDNA showed several nucleotide substitutions including alteration of the initiation codon of the NADH dehydrogenase 5 gene. Some of these nucleotide substitutions might contribute to the phenotypic expression of Pearson's syndrome synergistically with the deletion. PMID- 8356011 TI - Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency. AB - Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of fatty acid beta-oxidation. Its diagnosis has been made based on the reduced activity of palmitoyl-CoA dehydrogenation, i.e., in fibroblasts. We previously showed that in immunoblot analysis, an LCAD band of normal size and intensity was detected in fibroblasts from all LCAD-deficient patients tested. In the present study, we amplified via polymerase chain reaction and sequenced LCAD cDNA from three of these LCAD-deficient cell lines, and found perfectly normal LCAD sequences in two of them, indicating that at least these patients were not deficient in LCAD. The third patient was homozygous for an A to C substitution at 997, although it is unknown whether or not 997-C is a normal polymorphism. Although the LCAD sequence data were puzzling, a new enzyme, very-long-chain acyl-CoA dehydrogenase (VLCAD), was recently identified. Because VLCAD also has high activity with palmitoyl-CoA as substrate, it was possible that defective VLCAD may cause reduced palmitoyl CoA dehydrogenating activity. We performed immunoblot analysis of VLCAD in six "LCAD-deficient" patients; VLCAD was negative in three of them, two of whom had a normal LCAD cDNA sequence. These results indicated that a considerable number of the patients who had previously been diagnosed as having LCAD deficiency in fact have VLCAD deficiency. PMID- 8356012 TI - Pretreatment with monosialoganglioside GM1 protects the brain of fetal sheep against hypoxic-ischemic injury without causing systemic compromise. AB - The purpose of this study was to determine whether prophylaxis with monosialoganglioside GM1 can protect the fetus from hypoxic-ischemic encephalopathy in utero. Because some protective strategies can compromise the fetus, the effect of GM1 treatment on metabolic status and blood pressure was also evaluated. Chronically instrumented near-term fetal sheep (119-133 d) were subjected to 30 min of severe cerebral ischemia. Six were given 30 mg/kg GM1 through the umbilical vein 2 h before insult followed by continuous infusion of 30 mg/kg/d over the next 60 h, and these were compared with seven vehicle-treated control sheep. The time course of electrocorticographic activity and cytotoxic edema within the parasagittal cortex were determined with real-time spectral analysis and continuous impedance measurements, respectively. Histologic outcome was assessed 72 h later. Pretreatment with GM1 improved recovery of primary edema, reduced the duration of epileptiform activity (15 +/- 2 versus 31 +/- 5 h; p < 0.05) and the magnitude of secondary edema (p < 0.05). At 72 h, histologic damage was reduced, particularly in the cortex (p < 0.05) and hippocampus (p < 0.01), and residual electrocorticographic activity was increased in the GM1 treated group (-5 +/- 1 versus -9 +/- 3 dB, p < 0.01). GM1 infusion did not alter arterial blood pressure or metabolic status. These results indicate that GM1 can protect the fetal brain against hypoxic-ischemic injury without causing hypotension or metabolic compromise. PMID- 8356013 TI - Scavengers of free oxygen radicals in combination with magnesium ameliorate perinatal hypoxic-ischemic brain damage in the rat. AB - The effect of oxygen radical scavengers in combination with magnesium administered after a hypoxic-ischemic insult was evaluated in a model of perinatal brain damage. A mixture of scavengers of oxygen-derived free radicals (L-methionine, 0.2 g; mannitol, 0.5 g) and magnesium sulfate (0.3 g) per kg body weight was given to 34 1-wk-old rat pups immediately after a session of unilateral carotid artery ligation and 2 h of hypoxia (8% O2 in N2). Thirty-four littermates served as controls; they received a placebo. At 3 wk of age, there was a significantly smaller reduction of hemisphere weight ipsilateral to the ligation in the treated animals compared with the controls (0.7 versus 8.8% of contralateral hemisphere weight median values, p < 0.01). The difference was especially marked for the most severe degrees of brain damage. Only one of the 34 treated animals, compared with 13 of 34 control animals, had a reduction of ipsilateral hemisphere weight > 25%. The protection offered by the mixture used was larger than in previously published studies using this model and treatment after the hypoxic exposure with only one protective agent. It is concluded that a combination of oxygen radical scavengers and magnesium administered in the phase of resuscitation mitigates perinatal postasphyxial brain damage in the rat. An additive protective effect of different therapeutic strategies on the brain damage may be present in this situation. PMID- 8356014 TI - Differential gene expression of antioxidant enzymes in the perinatal rat lung. AB - It has been previously demonstrated that the developing rat lung markedly increases its catalase (CAT) and glutathione peroxidase (GP) activities during the final 10 to 15% of gestation. In the present studies, we tested whether four major antioxidant enzymes (AOE) in perinatal rat lungs might share a similar pattern of developmental AOE gene expression via a pretranslational mechanism. The left lungs of 18-d to term fetuses and early postnatal rat pups were used to measure the concentrations of AOE mRNA by solution hybridization and the right lungs of the same group of animals were assayed for AOE activities. Results revealed differential AOE gene expression in developing rat lungs. Whereas the CAT and GP activities progressively increased prenatally, the superoxide dismutase (SOD) activity either declined [copper-zinc SOD (Cu, ZnSOD)] or remained constant [manganese SOD (MnSOD)] in late gestation. Postnatally, Cu,ZnSOD and CAT activities progressively increased, whereas MnSOD remained constant and GP activity declined slightly. For Cu,ZnSOD, MnSOD, and CAT, the activity changes were generally consistent with the patterns of changes in their mRNA concentrations in both the prenatal and postnatal period, but for GP they were not. At the time of birth, however, the mRNA levels of Cu,ZnSOD and CAT decreased approximately 40%, whereas their enzyme activities increased. For MnSOD, only a slight rise in mRNA level was observed versus approximately 100% increase in its activity at the time of birth. These findings suggest that the AOE are not coordinately regulated, and that developmental regulation of AOE gene expression in the perinatal rat lung is complex and likely exerted at different levels of regulation. PMID- 8356015 TI - Intrinsic microbicidal activity and pulmonary hypertension in isolated newborn piglet lungs. AB - The lung appears to be one of the dominant sites of bacterial clearance from the blood of infant piglets. Part of the lung bacterial clearance involves activation of an oxygen radical bactericidal mechanism that may be central to induction of acute pulmonary hypertension. The present study determined whether this bactericidal activity was intrinsic to resident lung cells. Isolated piglet lung preparations perfused with blood-free salt solution were used to delineate the amount of group B streptococci (GBS) extracted and killed upon transit through pulmonary vasculature. Approximately 45% of infused GBS was deposited in the lung during a single pulmonary transit, whereas nearly 40% of the organisms sequestered in the lung were killed within a 30-min period. Pretreatment with dimethylthiourea, a scavenger of hydroxyl radical that inhibits GBS-induced pulmonary hypertension, attenuated both bacterial uptake and killing to similar extents. Along with its deposition in the lung, GBS also induced concentration dependent increases in total pulmonary resistance, which were related principally to increases in upstream arterial resistance. Lung weight also increased in a concentration-dependent manner. Both the increase in total pulmonary resistance and lung weight were temporally related to elevation in perfusion medium content of the stable thromboxane degradation product, thromboxane B2. Pretreatment with indomethacin, a prostaglandin H synthase inhibitor, or sodium(E)-3[4-(1 imidazolyl-methyl)phenyl]-2-propenoic acid a thromboxane synthase inhibitor, reduced GBS-induced pulmonary hypertension and edema. These results suggest that, in isolated piglet lungs, GBS evokes an intrinsic bactericidal response residing within lung cells, probably pulmonary intravascular macrophages, which may be responsible for the initiation of pulmonary hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356016 TI - The effects of hypoxic acidemia on left ventricular end-systolic elastance in fetal sheep. AB - Using the conductance catheter technique, we measured the effects of hypoxic acidemia on left ventricular end-systolic elastance in anesthetized, 133-d gestation, in utero fetal sheep (n = 7). Conductance and Millar catheters were introduced into the left ventricle through a carotid artery cutdown. Fetuses were rendered progressively hypoxic and acidemic by placental embolization with repeated injections of 5 x 10(5) 50-microns plastic spheres every 15 min via a catheter placed in the fetal abdominal aorta. We recorded pressure-volume data and arterial blood gases at 15-min intervals. End-systolic elastance was computed using a single-beat method of extrapolating maximum isovolumic pressure. A mean of five boluses was required to cause fetal death. Placental embolization caused progressive fetal acidemia. Mean baseline fetal arterial pH was 7.32 +/- 0.06 (mean +/- SD) and gradually decreased with embolization (p < 0.0001). A linear relationship was found to exist between elastance and pH with a mean decrease of 0.46 kPa/mL per 0.1-unit drop in pH (r = 0.96; p < 0.0001). Despite the decrease in end-systolic elastance, stroke volume and left-ventricular output were maintained due to a parallel decrease in afterload. The decrease in end-systolic elastance was gradual and extended over the entire clinically important range of pH, rather than being a terminal event. This study, which, to our knowledge, is the first to use the conductance catheter to measure fetal left ventricular function demonstrates that hypoxic acidemia adversely affects myocardial contractility assessed by end-systolic elastance. PMID- 8356017 TI - Hemodynamic parameters of stage 20 to stage 35 chick embryo. AB - Hemodynamic parameters of the chick embryo from stage 20 (3 d of a 21-d incubation) up to stage 35 (8 d) are described. Normal values of dorsal aortic flow velocity wave forms were measured with a 20-MHz directional-pulsed Doppler velocity meter that was validated to be accurate above 5 mm/s. An analysis of variance was carried out for each of the flow velocity parameters. The correlation coefficient that represents the reproducibility was satisfactory (r > 0.90). There was a 17-fold rise in mean dorsal aortic blood flow (mm3/s). Heart rate doubled from 123 +/- 12 to 239 +/- 8 bpm, and stroke volume increased from 0.14 +/- 0.08 to 1.28 +/- 0.55 mm3. A stage-related rise was seen in peak systolic and mean velocities and peak acceleration. These data may serve as a basis for flow velocity wave form investigation and interpretation in developmental stages of cardiac malformations. PMID- 8356018 TI - Sympathoadrenal, metabolic, and regional blood flow responses to cold in fetal sheep. AB - Because environmental temperature falls when the fetus is delivered from the uterus, the role of cold in stimulating cardiovascular and sympathoadrenal responses at the time of birth was examined in fetal lambs. In eight fetuses (gestational age 140 +/- 2 d), catheters were inserted into hind-limb and neck arteries and veins, and into an umbilical vein. After returning the fetus to the uterus and administering a muscle relaxant (succinylcholine chloride), blood gases, glucose and lactate concentrations, and plasma catecholamine and atrial natriuretic peptide concentrations were measured. Fetal combined ventricular output and organ blood flows were measured by the radionuclide-labeled microsphere technique. Measurements were repeated after delivering the fetus into a warm water bath (40 degrees C) and at 15 and 30 min after the bath temperature was cooled to 25 degrees C. Fetal cooling stimulated a sympathoadrenal response, which was manifested by an immediate increase in heart rate and arterial blood pressure, a rise in atrial natriuretic peptide, and modest increase in norepinephrine concentration. Contrary to earlier reports that investigated the effect of cold on fetal lambs using an intrauterine cooling coil, we did not find a decrease in fetal arterial oxygen tensions and pH, an increase in plasma glucose and lactate concentrations, or changes in fetal oxygen consumption. Combined ventricular output did not increase with cooling, and blood flow to most organs did not change significantly; however, blood flow to the skin decreased markedly, particularly in the lower body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356019 TI - Carotid, not aortic, chemoreceptors mediate the fetal cardiovascular response to acute hypoxemia in lambs. AB - The fetal cardiovascular response to acute hypoxemia consists of a decrease in heart rate, a variable change in mean arterial pressure, and an increase in peripheral vascular resistance. This response is mediated by the arterial chemoreceptors. To determine whether chemoreceptors in the carotid artery or in the aorta mediate the fetal cardiovascular response to acute hypoxemia, we studied the response to acute hypoxemia in fetal lambs at 125 to 130 d of gestation after selective carotid (six fetuses) or aortic (five fetuses) denervation. One to 3 d after insertion of catheters, hypoxemia was induced by inflating a balloon occluder around the ewe's hypogastric artery or by giving the ewe 95% N2 and 5% O2 to breathe. The chemoreflex response was measured as decrease in heart rate per decrease in Hb O2 saturation. To validate our results, we also studied the response to chemical stimulation of the chemoreceptors by injection of sodium cyanide into the inferior vena cava. We found that carotid denervation abolished the heart rate and peripheral vascular resistance responses to hypoxemia but that aortic denervation did not. Responses after injection of sodium cyanide were similar to those seen during acute hypoxemia. We conclude that the carotid chemoreceptors, and not the aortic chemoreceptors, mediate the fetal cardiovascular response to acute hypoxemia. PMID- 8356020 TI - Brainstem bilirubin toxicity in the newborn primate may be promoted and reversed by modulating PCO2. AB - The auditory brainstem response (ABR) was monitored during infusion of bilirubin in six ventilated newborn rhesus monkeys (138-145 d gestation) while acute changes in pH were produced by varying inspired CO2. Prolonged respiratory acidosis without bilirubin infusion produced minimal changes in the ABR (one animal). CO2 exposure, usually initiated when the bilirubin level reached approximately 20 mg/dL, decreased arterial pH to values ranging from 6.85 to 7.10. ABR changes, including prolongation of the wave II-IV peak to peak intervals and decreased wave amplitudes, first developed 2-4 h after initial exposure to CO2. Total and unbound bilirubin levels at this time ranged from 376 to 564 mumol/L (22-33 mg/dL) and 38 to 65 nmol/L (2.5-3.8 micrograms/dL), respectively. Correction of respiratory acidosis produced partial to complete reversal of ABR changes within 3 to 20 min. Reexposure to CO2 immediately reproduced the ABR abnormality. Production and reversal of the abnormal ABR was obtained through two to three cycles in three animals. Thus, when the brainstem bilirubin level was near the threshold for toxicity, the effect of changes in PCO2 on the ABR were immediate, suggesting that auditory pathway toxicity is initially mediated by a reversible pH-dependent bilirubin-membrane complex. In contrast to humans, in monkeys auditory toxicity appeared to be a late manifestation of bilirubin toxicity, inasmuch as all monkeys were obtunded and apneic 30-70 min before ABR abnormalities appeared. Notwithstanding these limitations, the results support the hypothesis that bilirubin toxicity can be both promoted and reversed by modulating brain pH. PMID- 8356021 TI - Glucose but not a mixed amino acid infusion regulates plasma insulin-like growth factor-I concentrations in fetal sheep. AB - The influence of fetal glucose and amino acid supply on the regulation of fetal plasma IGF-I levels was investigated in fetuses from starved ewes. Paired maternal and fetal blood samples were taken during an initial 2-d control period, after 48 h of maternal starvation, during a 24-h fetal infusion of glucose (n = 6) or an amino acid mixture (Synthamin 17, n = 5) with continued starvation, and after 48 h of maternal refeeding. After 48 h of starvation, maternal and fetal plasma IGF-I, insulin, and blood glucose fell significantly in both groups compared with control values (IGF-I for glucose group: maternal, -18.53 +/- 6.60; fetal, -5.23 +/- 1.81 nmol/L; amino acid group: maternal, -18.2 +/- 6.97, fetal, 5.12 +/- 1.61 nmol/L; both p < 0.05). Fetal glucose but not mixed amino acid infusion raised fetal plasma IGF-I, insulin, and blood glucose to near control values (glucose group fetal IGF-I, -1.77 +/- 1.98; amino acid group, -5.93 +/- 2.22 nmol/L; both p < 0.05). Maternal plasma IGF-I remained depressed during glucose infusion (-16.33 +/- 8.32 nmol/L), but continued to fall in the amino acid group (-21.41 +/- 8.20 nmol/L, p < 0.05). After 48 h of maternal refeeding, all values had returned to near control values for both groups (glucose group IGF I: maternal, -5.2 +/- 3.86; fetal, 0.01 +/- 2.2; nmol/L; amino acid group: maternal, -11.66 +/- 3.2; fetal, -0.70 +/- 2.61 nmol/L). We conclude that in the ovine fetus glucose may have a more important role than amino acids in the regulation of fetal plasma IGF-I. PMID- 8356022 TI - In vitro insulin-like growth factor-I, growth hormone, and insulin resistance occurs in symptomatic human immunodeficiency virus-1-infected children. AB - Poor growth is a common feature of symptomatic children (Centers for Disease Control stage P2) infected with human immunodeficiency virus-1 (HIV-1). However, several previous studies have failed to show any relationship between serum hormone levels and poor growth. To assess the roles of hormone deficiency and hormone resistance in the development of poor growth in HIV-1-infected children, we studied six asymptomatic Centers for Disease Control stage P1 [height SD score = 0.01 +/- 1.0 (mean +/- SD)], 10 P2 (height SD score = -2.0 +/- 1.0), and six short, normal children (height SD score = -2.4 +/- 1.2). Mean weight:height SD scores were similar in all three groups, suggesting that gross nutritional status did not differ between groups. There were no significant differences between groups with respect to mean plasma levels of IGF-I, thyroid hormones, TSH, and cortisol. As an index of hormone sensitivity, we quantified in vitro colony formation of erythroid progenitor cells, isolated from peripheral blood of study subjects, in response to IGF-I, growth hormone (GH), and insulin. P2 subjects had a quantitative mean reduction in erythroid progenitor cells colony formation in response to IGF-I of 32% compared with P1 subjects (p = 0.001 by analysis of variance) and 21% compared with controls (p = 0.006); in response to GH of 21% compared with controls (p = 0.015); and in response to insulin of 35% compared with P1 subjects (p = 0.038) and 34% compared with controls (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356023 TI - Influence of treatment on the maturation of the somesthetic pathway in infants with primary congenital hypothyroidism during the first year of life. AB - To assess the influence of treatment on the development of the somesthetic pathway in infants with congenital hypothyroidism receiving early treatment, median nerve somatosensory evoked potentials were measured during the 1st y of life. Twenty-nine infants were studied with six to seven somatosensory evoked potential tests per infant. The cervical latency (N13) divided by arm length and the first (N19) and second (N32) cephalic latencies as well as N13-N32 latency were measured. At diagnosis, all components showed a small but significant delay, which was not related to thyroxine (T4) levels before treatment. During treatment, T4 ranged from 50 to 290 nmol/L. At 12 mo, the cervical latency divided by arm length had normalized, whereas N19 and N13-N32 were more abnormal than at diagnosis. For N19, these abnormalities were related to a slow initial rise of T4 (< or = 100 nmol/L after 1 wk of treatment) and the initial N19 values. Abnormal N13-N32 values were associated with high T4 values during treatment (> 200 nmol/L) and the type of congenital hypothyroidism (partial or total deficiency in T4 production). Induction of therapy with l-triiodothyronine rather than l-thyroxine and the occurrence of low T4 values (< 100 nmol/L) after the 4th wk of therapy had no such effect. Our data suggest that, for normal CNS development, euthyroidism should be reached as soon as possible by adequate induction therapy. Thereafter, T4 supplementation should be strictly dosed, keeping the serum T4 values within narrow limits around the mean normal for age, because overtreatment, like initial undertreatment, may lead to CNS abnormalities at the end of the first year. PMID- 8356024 TI - The role of I and B in peritonitis associated with the nephrotic syndrome of childhood. AB - Children with nephrotic syndrome (NS) are susceptible to bacterial infections, including primary bacterial peritonitis. Immunologic abnormalities associated with NS include low serum levels of the complement proteins I and B of the alternative complement pathway. We developed a novel and highly sensitive enzyme immunoassay using murine MAb to I and B to quantitate urinary concentrations of these proteins. We studied 22 patients with minimal change NS, including seven with a history of peritonitis (1.6 +/- 0.3 episodes, mean +/- SEM) and 15 without such a history. The two groups did not differ significantly in age, sex, race, age at onset of disease, or duration of disease. Children with minimal change NS complicated by peritonitis had 1) increased urinary excretion of both I (p < 0.05) and B (p < 0.05) in relapse versus remission, 2) greater excretion of I in both relapse (p < 0.01) and remission (p < 0.05) compared with patients without peritonitis, 3) greater excretion of B in relapse compared with patients without peritonitis (p < 0.05), and 4) decreased plasma levels of I compared with patients without peritonitis and controls (p < 0.01) and decreased plasma levels of B compared with controls. Increased urinary excretion of I correlated with decreased plasma levels of I (r = 0.88, p < 0.001). These data support our initial hypothesis that depressed plasma concentrations of these proteins of the alternative complement pathway may predispose patients with minimal change NS to peritonitis and that urinary loss of these proteins is a tenable mechanism. PMID- 8356025 TI - Renal handling of carnitine in secondary carnitine deficiency disorders. AB - Reduced plasma and tissue concentrations of carnitine, a cofactor required for fatty acid oxidation, are present in patients with inherited disorders of mitochondrial acyl-CoA oxidation that are associated with accumulations of acylcarnitines. To determine whether the secondary carnitine deficiency in these patients is due to excessive urinary loss of acylcarnitines, the development of carnitine deficiency was examined in patients with four different acyl-CoA oxidation disorders, including medium-chain and long-chain fatty acyl-CoA dehydrogenase deficiencies, isovaleric acidemia, and propionic acidemia. After a 3-mo period of treatment with oral carnitine to raise plasma total carnitine concentrations to or above normal, patients were started on a carnitine-free diet and the changes in plasma total and free carnitine levels and urinary total and free carnitine excretion were followed for 5 d. Patients with all four disorders showed a return of plasma carnitine levels and urinary carnitine excretion to baseline within 2 to 4 d. The rapidity of these changes could not be explained solely by excessive acylcarnitine wasting. Continued excretion of free carnitine in all patients indicated the additional presence of an impairment in renal transport of free carnitine. Consistent with this interpretation, estimates of renal thresholds for free carnitine gave values that were less than that for a control child in all four disorders and ranged as low as one half those reported in normal individuals. These results suggest that secondary carnitine deficiency in the acyl-CoA oxidation disorders is due to indirect as well as direct effects of accumulated acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356027 TI - A season of new challenges. 4th Annual Fall Institute. Oncology Nursing Society. Seattle, Washington, October 29-31, 1993. Program. PMID- 8356026 TI - Evidence for human placental synthesis of 24,25-dihydroxyvitamin D3 and 23,25 dihydroxyvitamin D3. AB - The two principal dihydroxylated metabolites of the vitamin D prohormone 25 hydroxyvitamin D3 [25(OH)D3] are 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3, the active hormone] and 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3, a putative regulator of developmental bone formation]. Although several studies have demonstrated placental synthesis of 1,25(OH)2D3 from 25(OH)D3, placental production of 24,25(OH)2D3 has not been thoroughly investigated. Therefore, we studied 25(OH)D3 metabolism in term human placenta using a villous explant model and cultures of isolated trophoblast and villous mesenchymal cells. We determined that both vitamin D-replete and vitamin D-deficient trophoblast metabolize 25(OH)D3 predominantly via 24-hydroxylation. Placental 24,25(OH)2D3 was identified by cochromatography with authentic standard on four different HPLC systems, scanning UV spectrophotometry profile of the metabolite, sensitivity to periodate cleavage, and mass spectrometry of the putative placental 24,25(OH)2D3 and its periodate cleavage product. We also identified for the first time placental synthesis of 23,25(OH)2D3 using cochromatography with authentic standard on two different HPLC systems, scanning UV spectrophotometry, resistance to periodate cleavage, and mass spectrometry. When trophoblast was incubated for up to 4 h with physiologic concentrations of [3H]25(OH)D3 (6 nM) significant amounts of [3H]24,25(OH)2D3 were produced, but [3H]1,25(OH)2D3 could not be consistently detected. In contrast, when we incubated trophoblast with supraphysiologic concentrations of 25(OH)D3 (6-10 microM), both 24,25(OH)2D3 and 1,25(OH)2D3 were synthesized. These results provide unequivocal evidence for placental synthesis of both 24,25(OH)2D3 and 23,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356028 TI - Structures of the "open" and "closed" state of trypanosomal triosephosphate isomerase, as observed in a new crystal form: implications for the reaction mechanism. AB - The structure of trypanosomal triosephosphate isomerase (TIM) has been solved at a resolution of 2.1A in a new crystal form grown at pH 8.8 from PEG6000. In this new crystal form (space group C2, cell dimensions 94.8 A, 48.3 A, 131.0 A, 90.0 degrees, 100.3 degrees, 90.0 degrees), TIM is present in a ligand-free state. The asymmetric unit consists of two TIM subunits. Each of these subunits is part of a dimer which is sitting on a crystallographic twofold axis, such that the crystal packing is formed from two TIM dimers in two distinct environments. The two constituent monomers of a given dimer are, therefore, crystallographically equivalent. In the ligand-free state of TIM in this crystal form, the two types of dimer are very similar in structure, with the flexible loops in the "open" conformation. For one dimer (termed molecule-1), the flexible loop (loop-6) is involved in crystal contacts. Crystals of this type have been used in soaking experiments with 0.4 M ammonium sulphate (studied at 2.4 A resolution), and with 40 microM phosphoglycolohydroxamate (studied at 2.5 A resolution). It is found that transfer to 0.4 M ammonium sulphate (equal to 80 times the Ki of sulphate for TIM), gives rise to significant sulphate binding at the active site of one dimer (termed molecule-2), and less significant binding at the active site of the other. In neither dimer does sulphate induce a "closed" conformation. In a mother liquor containing 40 microM phosphoglycolohydroxamate (equal to 10 times the Ki of phosphoglycolohydroxamate for TIM), an inhibitor molecule binds at the active site of only that dimer of which the flexible loop is free from crystal contacts (molecule-2). In this dimer, it induces a closed conformation. These three structures are compared and discussed with respect to the mode of binding of ligand in the active site as well as with respect to the conformational changes resulting from ligand binding. PMID- 8356029 TI - Conformational deformation in deoxymyoglobin by hydrostatic pressure. AB - Pressure effect on the equilibrium conformation in sperm whale deoxymyoglobin and its volume fluctuation are studied by the normal mode analysis and strain tensor analysis. The pressure-induced deformation of interhelix regions are found to be remarkably more compressed than the other parts of the molecule. The intrahelix compressibility is shown to be relatively small. We also calculate the compressibility of the three hydrophobic clusters, located at the bottom, distal, and proximal side of the heme. Its value is found to decrease in the indicated order. The average compressibility of these hydrophobic clusters is less than the average interhelix compressibility, even though there are large cavities in these clusters. In order to study overall deformation, we define a linear compressibility and calculate it for all pairs of C alpha atoms. The pressure induced deformation is observed to be heterogeneous also in this analysis. The calculated root-mean-square displacement of the constituent atoms in the equilibrium conformation at 1,000 atm from those at 0 atm is 0.12 A, which is much smaller in magnitude than the average value of the atomic fluctuations at room temperature. In the water solvent, the volume excluded by the protein molecule in the equilibrium conformation is reduced by 0.9%, when the pressure is raised from 0 to 1,000 atm. The calculated magnitude of the root-mean-square volume fluctuation is 0.3% of the excluded volume at room temperature. The square of the volume fluctuation is given as a sum of contributions from individual normal modes. Contributions from low frequency normal modes are found to dominate over those from higher frequency normal modes. The estimated value of the isothermal compressibility of deoxymyoglobin is 9.37 x 10(-12) cm2/dyn. PMID- 8356030 TI - Secondary structural features of modules M2 and M3 of barnase in solution by NMR experiment and distance geometry calculation. AB - Proteins consist of structural units such as globular domains, secondary structures, and modules. Modules were originally defined by partitioning a globular domain into compact regions, each of which is a contiguous polypeptide segment having a compact conformation. Since modules show close correlations with the intron positions of genes, they are regarded as primordial polypeptide pieces encoded by exons and shuffled, leading to yield new combination of them in early biological evolution. Do modules maintain their native conformations in solution when they are excised at their boundaries? In order to find answers to this question, we have synthesized modules of barnase, one of the bacterial RNases, and studied the solution structures of modules M2 (amino acid residues 24-52) and M3 (52-73) by 2D NMR studies. Some local secondary structures, alpha-helix, and beta-turns in M2 and beta-turns in M3, were observed in the modules at the similar positions to those in the intact barnase but the overall state seems to be in a mixture of random and native conformations. The present result shows that the excised modules have propensity to form similar secondary structures to those of the intact barnase. PMID- 8356031 TI - Localization of hydrogen-bonds within modules in barnase. AB - Proteins in eukaryotes are composed of structural units, each encoded by discrete exons. The protein module is one such structural unit; it has been defined as the least extended or the most compact contiguous segment in a globular domain. To elucidate roles of modules in protein evolution and folding, we examined roles of hydrogen bonds and hydrophobic cores, as related to the stability of these modules. For this purpose we studied barnase, a bacterial RNase from Bacillus amylolique-faciens. Barnase is decomposed into at least six modules, M1-M6; the module boundaries are identified at amino acid residues 24, 52, 73, 88, and 98. Hydrogen bonds are localized mainly within each of the modules, with only a few between them, thereby indicating that their locations are designed to primarily stabilize each individual module. To obtain support for this notion, an analysis was made of hypothetical modules defined as segments starting at a center of one module and ending at the center of the following one. We found that the hydrogen bonds did not localize in each hypothetical module and that many formed between the hypothetical modules. The native conformations of modules of barnase may be specified predominantly by interactions within the modules. PMID- 8356032 TI - Crystal structure of Escherichia coli TEM1 beta-lactamase at 1.8 A resolution. AB - The X-ray structure of Escherichia coli TEM1 beta-lactamase has been refined to a crystallographic R-factor of 16.4% for 22,510 reflections between 5.0 and 1.8 A resolution; 199 water molecules and 1 sulphate ion were included in refinement. Except for the tips of a few solvent-exposed side chains, all protein atoms have clear electron density and refined to an average atomic temperature factor of 11 A2. The estimated coordinates error is 0.17 A. The substrate binding site is located at the interface of the two domains of the protein and contains 4 water molecules and the sulphate anion. One of these solvent molecules is found at hydrogen bond distance from S70 and E166. S70 and S130 are hydrogen bonded to K73 and K234, respectively. It was found that the E. coli TEM1 and Staphylococcus aureus PC1 beta-lactamases crystal structures differ in the relative orientations of the two domains composing the enzymes, which result in a narrowed substrate binding cavity in the TEM1 enzyme. Local but significant differences in the vicinity of this site may explain the occurrence of TEM1 natural mutants with extended substrate specificities. PMID- 8356033 TI - Molecular dynamics study of structure and stability of a model coiled coil. AB - This paper employs methods used earlier to study helix propensity in a model alpha-helix. The methods are extended to simulations of a motif structure of the alpha-helical coiled coil, i.e., a structure with a simple amino acid sequence, containing only alanine, leucine, and valine, with leucine and valine forming hydrophobic contacts in the helix interface (positions "d" and "a"). Dynamic simulations of the model coiled-coil structure reproduce characteristic features of the coiled-coil motif seen in experimental studies. Free energy simulations were used to assess the change in stability of the model when a leucine pair or a valine pair in the helix interface was replaced with an alanine pair. A leucine pair at position d was found to contribute 3.4 kcal/mol to the stability of the coiled coil relative to an alanine pair, and a valine pair at position a was found to contribute 0.8 kcal/mol relative to an alanine pair. The value for the leucine pair agrees with reports in two experimental studies with molecules having different amino sequence. The value for the valine pair is reasonable given the smaller size of the valine side chain and the intrinsic low helix propensity of valine. No experimental value was available for comparison. PMID- 8356034 TI - An analysis of the conformational paths of citrate synthase. AB - Previous simulation studies have provided reaction pathways leading from the closed to the open form of citrate synthase. We now undertake a detailed analysis of these pathways using a variety of different tools including backbone dihedral angles, P-Curves helicoidal parameters, inter-helix geometrical parameters, and accessibility calculations. The results point to a relatively small number of residues, mostly in loop regions, which are responsible for the majority of the conformational changes observed. An important role is attributed to transient changes in the backbone which facilitate movement along the reaction coordinate. Comparisons between the two pathways show that they share many common features despite the different algorithms used to generate them. PMID- 8356035 TI - Normal mode analysis of mouse epidermal growth factor: characterization of the harmonic motion. AB - Normal mode analysis of mouse epidermal growth factor (mEGF) has been carried out at room temperature. The value of the lowest frequency is 4.1 cm-1. This mode corresponds to hinge-bending motion between the N-terminal and C-terminal domains of mEGF. This hinge-bending motion corresponds to the "mitten mode." In this motion, the N-terminal domain is almost rigid. However, the C-terminal domain is found to consist of three rigid segments. Two segments, C33-D46 and G51-R53, are observed moving in the same direction, but L47-W50 moves in the opposite direction. For this mode, the effective Young's modulus turned out to be 1.1 x 10(9) dyn.cm-2. This value is a little larger than that of the mode with the lowest frequency 4.4 cm-1 of BPTI. The difference may be related to the fraction of residues involved in beta-sheets in the molecule. Similar analyses are carried out for other low frequency modes. PMID- 8356036 TI - Levels of DNA polymorphism and divergence yield important insights into evolutionary processes. PMID- 8356037 TI - A new use for intracellular antibody expression: inactivation of human immunodeficiency virus type 1. PMID- 8356038 TI - Protein-DNA complexes: the cost of recognition. PMID- 8356040 TI - Peroxisome biogenesis in the yeast Hansenula polymorpha is controlled by a complex set of interacting gene products. AB - We have studied the genetic interactions between mutant alleles in 12 genes, designated PER1-PER12, which are essential for peroxisome biogenesis in the yeast Hansenula polymorpha. Recessive mutations in any of these genes determined three different morphological phenotypes: (i) complete absence of peroxisomes (Per-); (ii) presence of small peroxisomes in conjunction with a major fraction of peroxisomal matrix proteins in the cytosol (Pim-); and (iii) presence of peroxisomes with aberrant crystalline matrix substructure (Pss-). Extensive complementation analysis showed many cases of noncomplementation--that is, diploids that contained both wild-type and mutant alleles of two different PER genes were unable to grow on methanol and showed peroxisomal defects. The observed cases of unlinked noncomplementation appeared to be gene and allele specific and were predominantly observed at lower temperatures (cold sensitive). The genetic results obtained were used to formulate a model of PER gene product interactions. In this model, five PER gene products are key or core components of the complex. Other PER gene products appear to play a more peripheral role. PMID- 8356039 TI - Cloning a plant amino acid transporter by functional complementation of a yeast amino acid transport mutant. AB - Amino acids are transported across the plasma membrane of plant cells by proton amino acid symports. We report here the successful cloning of a neutral amino acid carrier by functional complementation. A histidine transport deletion mutant of Saccharomyces cerevisiae was transformed with an Arabidopsis thaliana cDNA library constructed in a yeast expression vector. Forty transformants, out of 10(5), allowed growth on a histidine-limiting medium. The acquired ability to grow on low histidine was shown to be strictly dependent on the protein encoded by the expression plasmid. Histidine and alanine transport activity were 10- to 20-fold greater in the transformants. The transport kinetics, inhibitor sensitivity, and substrate specificity match those of neutral system II, a neutral amino acid carrier we previously described in plasma membrane vesicles isolated from leaf tissue. The cDNA insert is 1.7 kb with an open reading frame that codes for a protein containing 486 amino acids with a calculated molecular mass of 52.9 kDa and three sites of potential N-linked glycosylation. Hydropathy analysis of the deduced amino acid sequence suggests this is an integral membrane protein with 10-12 membrane-spanning alpha-helices. Overall, the sequence of this amino acid carrier is not closely related to any other protein sequences in the GenBank data base. Interestingly, however, there are small regions of sequence that exhibit significant levels of similarity with at least seven other integral membrane proteins. PMID- 8356041 TI - Evidence for adaptive evolution of the G6pd gene in the Drosophila melanogaster and Drosophila simulans lineages. AB - Proponents of the neutral theory argue that evolution at the molecular level largely reflects a process of random genetic drift of neutral mutations. Under this theory, levels of interspecific divergence and intraspecific polymorphism are expected to be correlated across classes of nucleotide or amino acid sequences with different degrees of functional constraint, such as synonymous and replacement sites. Nucleotide sites with reduced polymorphism should show comparably reduced levels of interspecific divergence. To examine this hypothesis, we have sequenced 32 and 12 copies of the glucose-6-phosphate dehydrogenase (G6pd) gene in Drosophila melanogaster and Drosophila simulans, respectively. Both species exhibit similar levels of nucleotide polymorphism at synonymous sites. D. melanogaster shows two amino acid polymorphisms, one associated with the cosmopolitan allozyme polymorphism and a second with an allozyme polymorphism endemic to European and North African populations. In contrast, D. simulans shows no replacement polymorphism. While synonymous divergence between species is 10%, which is typical of other genes, there are 21 replacement differences. This level of amino acid sequence divergence, when contrasted with levels of amino acid polymorphism, silent polymorphism, and divergence, is in 10-fold excess over that expected under the neutral model of molecular evolution. We propose that this excess divergence reflects episodes of natural selection on G6pd resulting in fixation of advantageous amino acid mutations in these two recently separated lineages. PMID- 8356043 TI - Photochemically induced cataracts in rat lenses can be prevented by AL-3823A, a glutathione peroxidase mimic. AB - Oxidative stress is known to cause cataracts in lens culture systems and is believed to be an important factor contributing to human cataracts. In this communication, it is demonstrated that cataract development of cultured rat lenses produced as a result of photochemically induced oxidation in a 4% oxygen atmosphere similar to the native environment of the lens can be blocked by the transition metal complex AL-3823A. In this system, riboflavin is added to the medium as a photosensitizer. AL-3823A acts primarily as a glutathione peroxidase mimic, which catalytically metabolizes H2O2 and also has low superoxide dismutase like activity. Measurements of H2O2, O2.-, and OH. indicate that appreciable levels of the first two of these oxidants and low levels of OH. are produced by this photochemical stressing system. The H2O2 concentrations are similar to those found in some patients with cataracts. The development of cataracts was followed over a 96-hr period. Transparency, hydration, glyceraldehyde-3-phosphate dehydrogenase activity, and protein and nonprotein thiol were monitored. All parameters show marked changes during the 96-hr period. However, in the presence of 200 microM AL-3823A, no difference between control and light-exposed lenses was observed with respect to these parameters. The results suggest that in vivo human cataract development caused by oxidative stress may be prevented by compounds of this type. PMID- 8356042 TI - The synonymous substitution rate of the major histocompatibility complex loci in primates. AB - Because the divergence of many allelic lineages at the major histocompatibility complex (MHC) loci predates species divergence, standard methods of calculating synonymous substitution rates are not applicable to this system. We used three alternative methods of rate estimation: one based on the minimum number of substitutions (Dm), another on the nucleotide difference (Dxy), and the third on the net nucleotide difference (Dn). We applied these methods to the protein encoding sequences of primate MHC class I (A, B, and C) and class II (DRB1) genes. To determine the reliability of the different estimates, we carried out computer simulation. The distribution of the estimates based on Dxy or Dn is generally much broader than that based on Dm. More importantly, the Dm-based method nearly always has the highest probability of recovering true rates, provided that Dm is not smaller than 5. Because of its desirable statistical properties, we used the Dm-based method to estimate the rate of synonymous substitutions. The rate is 1.37 +/- 0.61 for A, 1.84 +/- 0.40 for B, 3.87 +/- 1.05 for C, and 1.18 +/- 0.36 for DRB1 loci, always per site per 10(9) years. Hence despite the extraordinary polymorphism, the mutation rate at the primate MHC loci is no higher than that of other loci. PMID- 8356044 TI - A closed curve is much more than an incomplete one: effect of closure in figure ground segmentation. AB - Detection of fragmented closed contours against a cluttered background occurs much beyond the local coherence distance (maximal separation between segments) of nonclosed contours. This implies that the extent of interaction between locally connected detectors is boosted according to the global stimulus structure. We further show that detection of a target probe is facilitated when the probe is positioned inside a closed circle. To explain the striking contour segregation ability found here, and performance enhancement inside closed boundaries, we propose the existence of a synergetic process in early vision. PMID- 8356045 TI - Molecular and structural composition of phospholipid membranes in livers of marine and freshwater fish in relation to temperature. AB - The compositions and physical states of the liver phospholipids of marine and freshwater fish adapted to relatively constant but radically different temperatures were investigated. Fish adapted to low temperature (5-10 degrees C) accumulated more unsaturated fatty acids than those in a warm (25-27 degrees C) environment. There were no measurable differences in the gross fatty acid compositions of the total liver phospholipids from identical thermal environments. Docosahexaenoic acid (22:6) did not seem to participate in the process of adaptation. Cold adaptation was coincidental with oleic acid (18:1) accumulation, preferentially in the phosphatidylethanolamine. Determination of the molecular species composition of phosphatidylethanolamine revealed a 2- to 3 fold and 10-fold increase in the level of 18:1/22:6 and 18:1/20:5 species, respectively. ESR spectroscopy revealed a 7-10% compensation in the ordering state of native phospholipids with temperature. Combination of 16:0/22:6 phosphatidylcholine with phosphatidylethanolamines of cold-adapted marine fish showed a drastic fluidization near the C-2 segment of the bilayer, but not in the deeper regions. An appropriate combination (75:25) of phosphatidylcholines from warmth-adapted marine fish with phosphatidylethanolamines from cold-adapted marine fish mimicked a 100% adaptational efficacy in the C-2 segment as compared with the phosphatidylethanolamines of warmth-adapted marine fish. A specific role of 18:1/22:6 phosphatidylethanolamine in controlling membrane structure and physical state with thermal adaptation is proposed. PMID- 8356047 TI - Plants transformed with a cistron of a potato virus Y protease (NIa) are resistant to virus infection. AB - An oligonucleotide carrying signals for translation initiation in plants was engineered upstream to a cDNA clone containing nucleotides 5812-7260 of the potato virus Y (PVY) genome. This fragment contains all but the first 100 5' terminal bases of the cistron encoding one of the PVY proteases (NIa) as well as the first 251 bases of the next cistron (NIb). Nicotiana tabacum cv. SR1 plants were transformed with this fragment. The presence of the NIa sequences in transformed plants was determined by hybridization or PCR, and its expression was ascertained by reverse transcription coupled to PCR. Plants expressing NIa were self-pollinated, and the R1 kanamycin-resistant progeny were rechecked for NIa expression. Several of these plants were found to be resistant to PVY infection, inasmuch as they did not develop symptoms for at least 50 days (the duration of the experiments), and no viral accumulation could be detected in their leaves by ELISA. All of the descendents of resistant homozygous R2 plants were also resistant. Several of the plants transformed with the last three cistrons of PVY (bases 5812-9704; NIa-NIb-coat protein) were also resistant to PVY. None of the transformed plants exhibited resistance to tobacco mosaic virus. Exposure of the plants to 35 degrees C for 48 hr prior to inoculation lowered, but did not abolish, resistance. PMID- 8356046 TI - Triplet structure of von Willebrand factor reflects proteolytic degradation of high molecular weight multimers. AB - High molecular weight (HMW) and low molecular weight (LMW) forms of von Willebrand factor (vWF) were isolated from normal human plasma in the presence of protease inhibitors. HMW and LMW vWF preparations were subjected to reduction of interdimeric disulfide bridges under mild reducing conditions. Following sodium dodecyl sulfate electrophoresis in 3% agarose, the vWF bands were detected by immunoblotting with a polyclonal rabbit anti-vWF antiserum as well as with two monoclonal antibodies directed against epitopes located in the NH2-terminal (MAb 418) or in the COOH-terminal (MAb 9) region of the vWF subunit. Our results suggest that the slowest migrating band of the dimeric triplet set of LMW vWF represents an asymmetric structure composed of an intact subunit to which one NH2 terminal and one COOH-terminal fragment are linked by disulfide bridges. The intermediate band of the first triplet of LMW vWF strongly reacted with MAb 9 but not with MAb 418, indicating that it represents a dimer of COOH-terminal fragments. The fastest migrating band of the same triplet is apparently a dimer of the NH2-terminal fragments because it reacted with MAb 418 but not with MAb 9. Each next higher family of triplets seems to contain one more asymmetric fragment of dimeric size. These results are compatible with a model according to which LMW forms of vWF are derived from HMW vWF by proteolytic cleavage in the circulating blood. PMID- 8356048 TI - Molecular mechanics calculations of the structures of polyamide nucleic acid DNA duplexes and triple helical hybrids. AB - Polyamide nucleic acids (PNAs) have emerged as useful agents for recognition of single- and double-stranded nucleic acids. Interresidue hydrogen bonds between the amide carbonyl nearest the nucleobase and chain NH moieties provide inherent stability to the helical conformation of PNA 1. Moving the amide carbonyl away from the nucleobase to the backbone, and replacing it with a methylene group, results in 2 lacking the stabilizing hydrogen bond. Oligomers of 2 do not interact with DNA. Modeling suggests that 2 displays a more extended conformation than 1, and nucleobase orientation is disrupted in 2 in the absence of a complementary DNA strand. This is in contrast to 1, which retains a centrosymmetric arrangement of nucleobases. Structures for 1-T10.DNA and (1 T10)2.DNA species spanned by a pyrimidine strand (D-loop) were constructed. In the triple helical (1-T10)2.DNA structure, the two PNA strands form the complementary Watson-Crick paired strand and the Hoogsteen base-paired strand in the major groove of the 1.DNA duplex. The PNA strands are proposed to bind antiparallel to one another in (1-T10)2.DNA structure. The factors suggested to account for the stability of this 2:1 complex are (i) a hydrophobic attraction between two PNA backbones and (ii) a favorable electrostatic effect resulting from replacement of a phosphodiester backbone by a neutral peptide backbone. PMID- 8356049 TI - Crystal structures of medium-chain acyl-CoA dehydrogenase from pig liver mitochondria with and without substrate. AB - The three-dimensional structure of medium-chain acyl-CoA dehydrogenase from pig mitochondria in the native form and that of a complex of the enzyme and a substrate (product) have been solved and refined by x-ray crystallographic methods at 2.4-A resolution to R factors of 0.172 and 0.173, respectively. The overall polypeptide folding and the quaternary structure of the tetramer are essentially unchanged upon binding of the ligand, octanoyl (octenoyl)-CoA. The ligand binds to the enzyme at the rectus (re) face of the FAD in the crevice between the two alpha-helix domains and the beta-sheet domain of the enzyme. The fatty acyl chain of the thioester substrate is buried inside of the polypeptide and the 3'-AMP moiety is close to the surface of the tetrameric enzyme molecule. The alkyl chain displaces the tightly bound water molecules found in the native enzyme and the carbonyl oxygen of the thioester interacts with the ribityl 2' hydroxyl group of the FAD and the main-chain carbonyl oxygen of Glu-376. The C alpha--C beta of the fatty acyl moiety lies between the flavin and the gamma carboxylate of Glu-376, supporting the role of Glu-376 as the base that abstracts the alpha proton in the alpha--beta dehydrogenation reaction catalyzed by the enzyme. Trp-166 and Met-165 are located at the sinister (si) side of the flavin ring at the surface of the enzyme, suggesting that they might be involved in the interactions with electron transferring flavoprotein. Lys-304, the prevalent mutation site found in patients with medium-chain acyl-CoA dehydrogenase deficiency, is located approximately 20 A away from the active site of the enzyme. PMID- 8356050 TI - Functional analysis of Arabidopsis thaliana rRNA gene and spacer promoters in vivo and by transient expression. AB - In eukaryotes, RNA polymerase I transcription is controlled by DNA elements located within the spacers that separate the tandemly arranged rRNA genes. Unlike rRNA coding sequences, the intergenic spacers evolve rapidly and have little sequence similarity even among closely related species. Nonetheless, the arrangement of functional elements, such as spacer promoters and enhancers, is thought to be highly conserved. Here, we identify spacer promoters in the plant Arabidopsis thaliana, thereby demonstrating their existence in both the plant and animal kingdoms. We also use an Arabidopsis transient expression system to perform transcriptional analysis of the ribosomal gene promoter. Spacer promoters share sequence similarity with the gene promoter from -91 to +22 relative to the transcription start site, +1. Deletion analysis shows that sequences required for RNA polymerase I transcription reside within these boundaries. Spacer sequences upstream of the gene promoter have only a small positive effect on transcription in transfected protoplasts but can increase transcription from a Xenopus ribosomal gene promoter in injected frog oocytes. This trans-kingdom enhancer effect further suggests that the functional elements within eukaryotic ribosomal genes are highly conserved. PMID- 8356051 TI - Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. AB - Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, induces endothelial proliferation in vitro and vascular permeability in vivo. The human transmembrane c-fms-like tyrosine kinase Flt-1 has recently been identified as a VEGF receptor. Flt-1 kinase has seven immunoglobulin-like extracellular domains and a kinase insert sequence, features shared by two other human gene-encoded proteins, kinase insert domain-containing receptor (KDR) and FLT-4. In this study we show that the mouse homologue of KDR, Flk-1, is a second functional VEGF receptor. Flk-1 binds VEGF with high affinity, undergoes autophosphorylation, and mediates VEGF-dependent Ca2+ efflux in Xenopus oocytes injected with Flk-1 mRNA. We also demonstrate by in situ hybridization that Flk-1 protein expression in the mouse embryo is restricted to the vascular endothelium and the umbilical cord stroma. VEGF and its receptors Flk-1/KDR and Flt-1 may play a role in vascular development and regulation of vascular permeability. PMID- 8356052 TI - A recombinant immunotoxin containing a disulfide-stabilized Fv fragment. AB - B3(dsFv)-PE38KDEL is a recombinant immunotoxin composed of the Fv region of monoclonal antibody B3 connected to a truncated form of Pseudomonas exotoxin (PE38KDEL), in which the unstable Fv heterodimer (composed of heavy- and light chain variable regions) is held together and stabilized by a disulfide bond [termed disulfide-stabilized Fv (dsFV)]. A computer modeled structure of the B3(Fv), made by mutating and energy minimizing the amino acid sequence and structure of McPC603, enabled us to identify positions in conserved framework regions that "hypothetically" could be used for disulfide stabilization without changing the structure or affecting antigen binding. This prediction was evaluated experimentally by constructing a disulfide-linked two-chain dsFv immunotoxin that was produced in Escherichia coli. The activity and specificity of this immunotoxin was indistinguishable from its single-chain Fv (scFv) counterpart, indicating that, as in B3(scFv), the structure of the binding region is retained in B3(dsFv). Because we introduced the stabilizing disulfide bond in between two framework residues in a position that is conserved in most Fv molecules, this method of linkage between the heavy- and light-chain variable regions should be generally applicable to construct immunotoxins and dsFv molecules using other antibodies. Furthermore, the finding that B3(dsFv) was much more stable at 37 degrees C in human plasma than B3(scFv) indicates that dsFvs are possibly more versatile for therapeutic application than scFvs. PMID- 8356054 TI - Facilitated distortion of the DNA site enhances EcoRI endonuclease-DNA recognition. AB - We have measured the binding of EcoRI endonuclease to a complete set of purine base analogue sites, each of which deletes one functional group that forms a hydrogen bond with the endonuclease in the canonical GAATTC complex. For five of six functional group deletions, the observed penalty in binding free energy is +1.3 to +1.7 kcal/mol. For two of these cases (replacement of adenine N7 with carbon) a single protein-base hydrogen bond is removed without deleting an interstrand Watson-Crick hydrogen bond or causing structural "adaptation" in the complex. This observation establishes that the incremental energetic contribution of one protein-base hydrogen bond is about -1.5 kcal/mol. By contrast, deletion of the N6-amino group of the inner adenine in the site improves binding by -1.0 kcal/mol because the penalty for deleting a protein-base hydrogen bond is outweighed by facilitation of the required DNA distortion ("kinking") in the complex. This result provides direct evidence that the energetic cost of distorting a DNA site can make an unfavorable contribution to protein-DNA binding. PMID- 8356053 TI - In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease. AB - Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi (CHOH)]2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val-->Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors. PMID- 8356055 TI - Association of the low molecular weight GTP-binding protein rap2B with the cytoskeleton during platelet aggregation. AB - The intracellular distribution of the low-molecular-weight GTP-binding protein rap2B was investigated in resting and agonist-activated human platelets. In both cases, platelets were lysed by Triton X-100, and cell fractions were obtained by differential centrifugations. Using a specific polyclonal antiserum, we found that rap2B in resting platelets was completely detergent-soluble. When platelets were aggregated with thrombin, the thromboxane analogue U46619, or the Ca(2+) ATPase inhibitor thapsigargin, a significant amount of rap2B became associated with the cytoskeleton. This association was paralleled by a decrease of rap2B in the Triton X-100-soluble fraction. Translocation of rap2B to the cytoskeleton strictly depended on platelet aggregation, and maximal incorporation was found when approximately 50% aggregation was measured. Inhibition of fibrinogen binding to the glycoprotein IIb-IIIa complex completely prevented the interaction of rap2B with the cytoskeleton. These results clearly demonstrate that changes in the intracellular localization of rap2B occur during platelet activation and represent evidence that this low molecular weight GTP-binding protein may be involved in platelet function. PMID- 8356056 TI - Improved prediction of protein secondary structure by use of sequence profiles and neural networks. AB - The explosive accumulation of protein sequences in the wake of large-scale sequencing projects is in stark contrast to the much slower experimental determination of protein structures. Improved methods of structure prediction from the gene sequence alone are therefore needed. Here, we report a substantial increase in both the accuracy and quality of secondary-structure predictions, using a neural-network algorithm. The main improvements come from the use of multiple sequence alignments (better overall accuracy), from "balanced training" (better prediction of beta-strands), and from "structure context training" (better prediction of helix and strand lengths). This method, cross-validated on seven different test sets purged of sequence similarity to learning sets, achieves a three-state prediction accuracy of 69.7%, significantly better than previous methods. In addition, the predicted structures have a more realistic distribution of helix and strand segments. The predictions may be suitable for use in practice as a first estimate of the structural type of newly sequenced proteins. PMID- 8356057 TI - Identification and characterization of an essential, activating regulatory element of the human SIS/PDGFB promoter in human megakaryocytes. AB - The SIS/PDGFB gene, encoding the B polypeptide of platelet-derived growth factor (PDGF-B), is transcriptionally activated (> 50 fold) in human K562 erythroleukemia cells when they are induced to differentiate into megakaryocytic cells by treatment with phorbol 12-myristate 13-acetate ("tetradecanoylphorbol acetate," TPA). A 250-bp PDGF-B gene promoter attached to a reporter gene was shown to reproduce this TPA-induced activation. In a series of mutants that we constructed, a 10-bp linker sequence was systematically moved across the 250-bp PDGF-B promoter sequence, and the effect upon luciferase reporter activity was measured to identify a site through which this TPA-induced transcriptional activation occurred. We identified a site, which we named the SIS proximal element (SPE), at positions -58 to -39 relative to the PDGF-B mRNA initiation site that was essential for the TPA-induced activation. The SPE site contains two repeated sequences (TCTC and CACC) arranged in an ABBA configuration. The SPE sequence was not found in the existing list of consensus sequences for transcription factor binding sites. Gel mobility-shift assays using an SPE oligonucleotide and K562 cell nuclear extracts showed three shifted complexes, one of which was formed only following TPA treatment of K562 cells. In a time course study, TPA induction of the endogenous PDGF-B mRNA and formation of the TPA-inducible complex occurred over the same time frame, and both events were specifically blocked by the addition of cycloheximide. The 20-bp SPE sequence was highly conserved (19/20) in both the cat and the mouse PDGF-B promoter, and conserved portions of the SPE sequence were also found at two sites within the human PDGF-A promoter. The role of the SPE in regulating the concurrent expression of the PDGF-B and PDGF-A genes in megakaryocytes, as well as various human tumor cells, is considered. PMID- 8356058 TI - Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes. AB - The Ras-related small GTP-binding proteins are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The interconversion of the active, GTP-bound form of the protein to the inactive, GDP-bound form is influenced by two types of regulatory proteins, those that alter the intrinsic GTPase activity of the GTP-binding protein and those that affect the rate of GDP/GTP exchange. By utilizing a subtractive hybridization approach, we have isolated a human gene encoding Ly-GDI, a protein that has striking homology to the product of a previously cloned gene, Rho-GDI, which inhibits GDP/GTP exchange on the Rho family of GTPases. In contrast to Rho GDI, which is ubiquitously expressed, Ly-GDI is expressed only in hematopoietic tissues and predominantly in B- and T-lymphocyte cell lines. The full-length Ly GDI cDNA encodes a 27-kDa protein which binds to RhoA and inhibits GDP dissociation from RhoA. Stimulation of T lymphocytes with phorbol ester leads to phosphorylation of Ly-GDI, suggesting an involvement of Ly-GDI in lymphocyte activation pathways. Cell type-specific regulators of the Ras-like GTP-binding proteins may provide one mechanism by which different cell types respond uniquely to signals transduced through the same cell surface receptor or may provide a way by which the GTP-binding proteins can be uniquely engaged by tissue-restricted receptors. PMID- 8356059 TI - Identification of CD4 and major histocompatibility complex functional peptide sites and their homology with oligopeptides from human immunodeficiency virus type 1 glycoprotein gp120: role in AIDS pathogenesis. AB - CD4 molecules interact with class II major histocompatibility complex molecules as a critical costimulatory signal in CD4+ cell immune activation. CD4 also recognizes a specific region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 forming a binding site for early stages of HIV-1 infection. We designed two software packages, AUTOMAT and CRITIC, which allowed us to identify similarities between regions of HIV-1 proteins and immunoregulatory protein sequences stored in data banks. In this report we have characterized (i) a pentapeptide, SLWDQ, found in both CD4 and HIV-1 gp120, which surprisingly had remained undetected in these two well-studied molecules until now, and (ii) an HLA sequence corresponding to the putative functional site of H2 I-A. We found that a region of gp120 (residues 254-263) known to be similar to a sequence in HLA class II beta chain overlaps this functional region. We showed experimentally that these two CD4 and HLA peptide segments inhibit CD4+ cell immune activation. There is strong inhibition (50% up to 80%) of immune activation by SLWDQ-containing gp120 segments and a lesser inhibition by the gp120 HLA-homologous segment. In addition, we found that SLWDQ induced in HIV-1 infected individuals a humoral (antibody) and cellular (cytotoxic T lymphocyte) immune reaction. We propose that these HIV-1 gp120 segments, together with the known CD4-binding region, may contribute to the HIV-1-induced immunosuppression by two mechanisms affecting CD4-HLA interaction during T-cell immune activation: autoimmune reaction toward CD4 and direct interference with the CD4-HLA costimulatory signal inducing CD4+ cell anergy with, as a consequence, generation of immunosuppression. PMID- 8356060 TI - Localization of E2A mRNA expression in developing and adult rat tissues. AB - E2A helix-loop-helix proteins are involved in the control of various developmental pathways. We show here by in situ hybridization that E2A transcripts are present in most embryonic and adult tissues. However, no E2A expression is detectable in heart and nonproliferative regions of the brain and spinal cord. Highest levels of E2A expression are found in the ependyma cell layer surrounding the cerebral ventricles in the embryonic rat brain. In addition, in the embryo, E2A transcripts were found in secretory cells of the pancreas, the bronchial tubes of the lung, glomeruli of the kidney, and the lining of the stomach. Interestingly, high levels of E2A transcripts are selectively found in the germinal center of the lymphatic nodules in the adult rat spleen. Thus, E2A, like its Drosophila homolog daughterless, is expressed in most tissues. The most notable feature of the E2A expression pattern is its high levels of expression in some areas of rapid cell proliferation and differentiation and in certain epithelial cell types. PMID- 8356061 TI - Transgenic mice containing a 248-kb yeast artificial chromosome carrying the human beta-globin locus display proper developmental control of human globin genes. AB - Transgenic mice were generated using a purified 248-kb yeast artificial chromosome (YAC) bearing an intact 82-kb human beta-globin locus and 148 kb of flanking sequence. Seventeen of 148 F0 pups were transgenic. RNase protection analysis of RNA isolated from the blood of 13 gamma- and beta-globin-positive founders showed that only the human beta-globin gene was expressed in the adult founders. Studies of F1 and F2 fetuses demonstrated that the genes of the beta locus YAC displayed the proper developmental switches in beta-like globin gene expression. Expression of epsilon- and gamma-globin, but not beta-globin, was observed in the yolk sac, there was only minor gamma and mostly beta expression in the 14-day liver, and only beta mRNA in the blood of the adult animals. Structural data showed that the locus was intact. These results indicate that it is now possible to dissect regulatory mechanisms within the context of an entire locus in vivo by using the ability to perform mutagenesis efficiently in yeast via homologous recombination, followed by purification of the altered YAC and its introduction into mice. PMID- 8356062 TI - Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I. AB - T cells control the majority of antigen-specific immune responses. Therefore, influencing the activation of the T-cell response in order to modify immune responsiveness is an obvious therapeutic goal. We have used a mouse model of response to Fel d I, the major cat protein allergen in humans, to explore the ability of peptides derived from Fel d I to inhibit T-cell-dependent immune responses to the peptides themselves and to larger polypeptides. T cells from B6CBAF1 mice respond to the Fel d I peptide IPC-2 after challenge with IPC-2. However, subcutaneous tolerization with IPC-2 prevents this response as measured by production of interleukins 2 and 4 and interferon gamma. Fel d I immunization of B6D2F1 mice results in T-cell responses primarily to one peptide derived from Fel d I. Injecting this peptide in soluble form inhibits T-cell activation (as measured by interleukin 2 production) and antibody production in Fel d I-primed animals when they are subsequently challenged with peptide in adjuvant. Most of the cat-allergic human T-cell response to Fel d I is specific for two peptides on one of its two chains. Immunization of B6CBAF1 mice with recombinant Fel d I chain 1 results in T-cell responses to the same peptides. Subcutaneous administration of these two peptides, which contain some, but not all, of the T cell epitopes from Fel d I chain I, decreases the T-cell response to the entire recombinant Fel d I chain 1. The ability to tolerize T-cell responses with subcutaneous injections suggests a practical approach to treating human diseases with peptides containing T-cell epitopes. PMID- 8356064 TI - Inhibition of CD10/neutral endopeptidase 24.11 promotes B-cell reconstitution and maturation in vivo. AB - The common acute lymphoblastic leukemia antigen [(CALLA) CD10, neutral endopeptidase 24.11 (NEP)] is a cell-surface zinc metalloprotease expressed by a subpopulation of early murine B-lymphoid progenitors and by bone marrow stromal cells that support the earliest stages of B lymphopoiesis. In previous in vitro studies in which uncommitted murine hematopoietic progenitors plated on a stromal cell layer differentiate into immature B cells, the inhibition of CD10/NEP increased early lymphoid colony numbers. To further characterize CD10/NEP function during lymphoid ontogeny in vivo, we utilized a Ly5 congenic mouse model in which the lymphoid differentiation of uncommitted hematopoietic progenitors from Ly5.1 donors was followed in sublethally irradiated Ly5.2 recipients treated with a specific long-acting CD10/NEP inhibitor (N-[L-(1-carboxy-2-phenyl)ethyl]-L phenylalanyl-beta- alanine (SCH32615)). The expression of Ly5.1, B220, and surface IgM (sIgM) was utilized to characterize donor-derived hematopoietic cells (Ly5.1+), B lymphocytes (B220+), and mature B cells (B220+ sIgM+) from the lymphoid organs of recipient animals treated with SCH32615 or vehicle alone. SCH32615-treated animals had higher percentages of Ly5.1+ donor splenocytes than animals treated with vehicle alone (16.9% vs. 10.4%, 63% increase, P = 0.013). Animals treated with the CD10/NEP inhibitor also had relatively more Ly5.1+ splenic B (B220+) cells than vehicle-treated animals (14.4% vs. 8.2%, 75% increase, P = 0.018). To more specifically characterize the effects of CD10/NEP inhibition on B-cell differentiation, Ly5.1+ splenocytes from animals treated with SCH32615 or vehicle alone were analyzed for coexpression of B220 and sIgM. Animals treated with the CD10/NEP inhibitor had a significantly higher percentage of mature donor B cells (Ly5.1+ B220+ sIgM+, 10.2% vs. 5.2%, 90% increase, P = 0.006) and a more modest relative increase in immature donor B cells (Ly5.1+ B220+ sIgM-, 4.7% vs. 3.4%, 38% increase, P = not significant). Taken together, these results suggest that CD10/NEP inhibition promotes the reconstitution and maturation of splenic B cells. Therefore, CD10/NEP may function to regulate B cell ontogeny in vivo by hydrolyzing a peptide substrate that stimulates B-cell proliferation and/or differentiation. PMID- 8356063 TI - Ferritin synthesis is controlled by iron-dependent translational derepression and by changes in synthesis/transport of nuclear ferritin RNAs. AB - Ferritin synthesis, maintained at a very low basal rate when extracellular iron levels are low, is elevated up to 50-fold when iron levels are increased. Previous examinations of this iron-dependent activation have concluded that changes in ferritin synthesis results from selective translational activation conferred by an "iron response element" that lies near the 5' terminus of all known ferritin mRNAs. By placing an iron response element in an optimal position in other mRNAs, we find the iron response element to be a potent translational repressor whose influence can only partially be abrogated under optimal inducing conditions. Further, we show that the 25- to 50-fold iron-mediated increase in ferritin synthesis results from coupling a 5- to 6-fold iron-dependent translational derepression with a similar 5- to 6-fold nuclear-dependent increase in mRNA level. PMID- 8356065 TI - Human mitochondrial carbonic anhydrase: cDNA cloning, expression, subcellular localization, and mapping to chromosome 16. AB - A full-length cDNA clone encoding human mitochondrial carbonic anhydrase (CA), CA V, was isolated from a human liver cDNA library. The 1123-bp cDNA includes a 55 bp 5' untranslated region, a 915-bp open reading frame, and a 153-bp 3' untranslated region. Expression of the cDNA in COS cells produced active enzyme. The 34-kDa precursor and 30-kDa mature form of CA V were identified on Western blots of COS-cell homogenates by a CA V-specific antibody raised to a synthetic peptide corresponding to the C-terminal 17 aa of CA V. Both 34-kDa and 30-kDa bands were also present in mitochondria isolated from transfected COS cells, whereas only the 30-kDa band was present in mitochondria isolated from normal human liver. The N-terminal sequence determined directly on the 30-kDa soluble CA purified from transfected COS cells indicated that processing of the precursor to mature human CA V involves removal of a 38-aa mitochondrial leader sequence. The 267-aa sequence deduced for mature human CA V shows 30-49% similarity to amino acid sequences of previously characterized human CAs (CA I-CA VII) and 76% similarity to the corresponding amino acid sequence deduced from the mouse cDNA. PCR analysis of DNAs from human-rodent somatic cell hybrids localized the gene for CA V to human chromosome 16, the same chromosome to which CA VII has previously been mapped. PMID- 8356066 TI - Identification of small GTP-binding rab proteins in human platelets: thrombin induced phosphorylation of rab3B, rab6, and rab8 proteins. AB - The activation of platelets by specific agonists is a tightly regulated mechanism that leads to the secretion of the dense- and alpha-granule contents. Platelets have been shown to possess small GTP-binding proteins thought to be involved in central biological processes; however, no rab proteins, which may regulate the exocytic process at different stages, have been reported. This study has shown that rab1, rab3B, rab4, rab6, and rab8 proteins, but not rab3A protein, were present in platelets and in endothelial cells. To probe their functional significance in platelets, rab3B, rab6, and rab8 proteins were further characterized with regard to their intracellular localization and their phosphorylation properties. Whereas rab3B protein was found to be mainly cytosolic, rab6 and rab8 proteins were preferentially targeted to the plasma membrane and to the alpha granules. The activation of platelets by thrombin, a potent inducer of secretion, resulted in the phosphorylation of rab3B, rab6, and rab8 proteins, whereas no phosphorylation was observed in the presence of prostaglandin E1, which stimulates cAMP-dependent protein kinase and inhibits the secretion process. These findings provide evidence that members of the subfamily of rab proteins, rab6 and rab8, are localized in platelets to one type of specific secretory vesicle, the alpha granule, and would suggest their possible implication in the secretion process through phosphorylation mechanisms. PMID- 8356067 TI - Masking generates contiguous segments of metal-coated and bare DNA for scanning tunneling microscope imaging. AB - To date, no microscopic methods are available to confirm scanning tunneling microscope (STM) images of DNA. The difficulties encountered in repeating these images may be attributed to inadequate distribution of molecules on the substrate, poor adhesion to the substrate, or the low conductivity of the molecules. However, these factors are difficult to assess in an STM experiment where they may act simultaneously. A method to isolate these factors involves partly masking the deposited molecules before coating them with a conductive film to produce adjacent segments of coated and bare DNA after the mask is removed. The coated DNA segments are conductive and mechanically stable to allow easy identification of DNA by the STM. Furthermore, the path of a molecule can be traced from a coated to an uncoated region to test STM imaging of bare DNA. Masked preparations of DNA deposited on platinum/carbon-coated mica and highly oriented pyrolytic graphite were examined with a tunneling current 1000 times lower than the usual nanoamps. The tip apparently displaces molecules adsorbed to graphite to preclude imaging whereas more stably bound DNA on platinum/carbon coated mica appears in reversed contrast. PMID- 8356069 TI - Mediation of osmoregulatory influences on neuroendocrine corticotropin-releasing factor expression by the ventral lamina terminalis. AB - Chronic exposure to a hyperosmolar challenge invokes coordinate, differential, and ostensibly adaptive alterations in the expression of mRNA encoding corticotropin-releasing factor (CRF) in the endocrine hypothalamus. Rats maintained on 2% (wt/vol) saline for 7 days displayed the expected reduction in CRF mRNA levels in the parvocellular neurosecretory compartment of the paraventricular nucleus, as well as a concomitant increase in CRF transcripts in oxytocin-containing magnocellular neurosecretory neurons. Also detected in salt loaded animals was a prominent induction of the immediate-early gene product Fos in magnocellular neurosecretory cell groups and in several brain regions that are known to provide major projections to the endocrine hypothalamus. These included a triad of cell groups making up the lamina terminalis of the third ventricle, and, to a lesser extent, catecholaminergic cell groups in the caudal brain stem. Discrete transections of descending projections from structures associated with the lamina terminals, as well as excitotoxin lesions centered in one lamina terminalis-associated structure, the organum vasculosum, abolished the effects of salt loading in both the magno- and parvocellular neurosecretory systems. Knife cuts in the lamina terminalis complex that spared only projections from the organum vasculosum region or cuts that disrupted ascending catecholaminergic projections failed to modify either effect of salt loading. The results suggest the existence of a simple circuit through which osmotic influences on gene expression in the magnocellular and parvocellular neurosecretory systems are effected. PMID- 8356068 TI - In vivo and in vitro evidence for slipped mispairing in mammalian mitochondria. AB - Slipped mispairing between repeated sequences during DNA replication is an important mutagenic event. It is one of several suggested mechanisms thought to be responsible for generating polymorphic regions and large-scale deletions found in mammalian mitochondrial DNA. In the porcine mitochondrial genome, a domain carrying a 10-bp tandemly repeated sequence displays a unique in vivo pattern of repeat copy number polymorphs. Upon passage in Escherichia coli, a recombinant plasmid containing this domain also displays a unique polymorphic pattern that is different from that seen in the animal. To test the hypothesis that these polymorphisms were slippage induced and that the different polymorphic patterns reflected differences in modes of replication, we performed a series of in vitro primer extension reactions. By utilizing either single- or double-stranded templates containing the repeat domain we were able to correlate in vitro generated repeat polymorphism patterns with those seen in the mitochondria or the bacteria, respectively, thus providing experimental evidence that slippage replication is responsible for a major class of mammalian mutations. PMID- 8356070 TI - Amino acid residues essential for biological activity of a peptide derived from a major histocompatibility complex class I antigen. AB - The stimulatory activity of peptides from the alpha 1 domain of the major histocompatibility complex (MHC) class I antigen on adipose cell glucose transport was previously shown to require a preformed, ordered conformation of the peptide. The two peptides studied previously were Dk-(61-85) (ERETQIAKGNEQSFRVDLRTLLRYY) and Dk-(69-85). We now show that systematic alanine substitution in Dk-(69-85) identifies residues that are essential for biological activity. Ordered structure of the peptides, estimated by circular dichroism, was found in all peptides with activity, but with a complex variety of spectra. Inactive peptides were in either a random coil or an ordered structure. Ordered structure, therefore, is not sufficient for activity. The peptides self-interact in the absence of cells and form aggregates that precipitate upon centrifugation. The tendency to aggregate is correlated with biological potency. Only MHC class I molecules have significant homology to the peptides studied here. The peptide self-interaction suggests that the biological effects in cells, which result from inhibition of receptor and transporter internalization, may be due to the binding (tantamount to self-interaction) of the peptide to the homologous sequences in the alpha 1 domain of the MHC class I molecule. PMID- 8356071 TI - The Src family tyrosine kinases are required for platelet-derived growth factor mediated signal transduction in NIH 3T3 cells. AB - Three members of the Src family of protein tyrosine kinases Src, Fyn, and Yes associate with the activated platelet-derived growth factor (PDGF) receptor in vivo. This interaction requires the Src homology 2 (SH2) domain of the Src family member and causes activation of the intrinsic activity of the Src family kinases. We microinjected cells with DNA encoding catalytically inactive forms of the Src and Fyn proteins and examined their effects on PDGF-mediated signaling in vivo. Kinase-inactive Src and Fyn inhibited PDGF-stimulated entry of cells into S phase, whereas kinase-active forms of the proteins had no inhibitory effects. An intact SH2 domain was required for inhibition. Furthermore, when kinase-inactive Fyn was comicroinjected with a plasmid expressing activated Ras, the cells could enter S phase, indicating that the expression of kinase-inactive Fyn did not damage cell viability. Injection of an antibody specific for Src, Fyn, and Yes also reduced signal transduction through the PDGF receptor but only when injected within 8 hr of PDGF stimulation. Together these results indicate that the ubiquitously expressed Src family members are required for PDGF-induced mitogenic signaling. PMID- 8356072 TI - Relevance of chemistry to conservation of isolated populations: the case of volatile leaf components of Dicerandra mints. AB - Chemical analysis of the essential oils of four congeneric species of mint plant (Dicerandra spp.) endemic to Florida revealed a pattern of chemical similarity and dissimilarity that would not have been predicted on morphological or geographic criteria. Dicerandra christmanii differs fundamentally from its congeners in that it produces fewer compounds and lacks the acyclic components. Yet D. christmanii is more closely similar to Dicerandra frutescens than to other Dicerandra species in morphological characters and geographic range. We conclude that the potential chemical value of a species should not be prejudged on the basis of nonchemical characters and that designation of surplus plant populations by conservationists should be resisted unless such populations have also been chemically studied. PMID- 8356073 TI - The N-terminal coiled-coil domain of beta is essential for gamma association: a model for G-protein beta gamma subunit interaction. AB - We have identified the N terminus of the beta subunit as an essential domain for G-protein beta gamma assembly. A C-terminal fragment, beta 1-(130-340), fails to bind gamma unless coexpressed with the complementary N-terminal fragment, beta 1 (1-129). Deletion of the N-terminal 33 residues of beta 1, a region identified by computer algorithm to favor coiled-coil formation, abolishes gamma 2 association. On the basis of these findings, we propose a coiled-coil model of beta gamma interaction and refine this by computer-assisted molecular modeling. The model is tested by further mutagenesis: reversing the charge of residues in beta 1 that are hypothesized to be involved in interhelical salt bridges precludes gamma association. Insertions in the coiled-coil region, which disrupt the proposed hydrophobic interface, prevent gamma association. This structural basis for beta gamma dimerization provides a starting point for the design of beta and gamma mutants that can be used to map regions in beta gamma critical for interactions with the alpha subunit, receptors, and effectors. PMID- 8356074 TI - Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex. AB - Although antibodies are highly specific, cross-reactions are frequently observed. To understand the molecular basis of this phenomenon, we studied the anti-hen egg lysozyme (HEL) monoclonal antibody (mAb) D11.15, which cross-reacts with several avian lysozymes, in some cases with a higher affinity (heteroclitic binding) than for HEL. We have determined the crystal structure of the Fv fragment of D11.15 complexed with pheasant egg lysozyme (PHL). In addition, we have determined the structure of PHL, Guinea fowl egg lysozyme, and Japanese quail egg lysozyme. Differences in the affinity of D11.15 for the lysozymes appear to result from sequence substitutions in these antigens at the interface with the antibody. More generally, cross-reactivity is seen to require a stereochemically permissive environment for the variant antigen residues at the antibody-antigen interface. PMID- 8356075 TI - Evolutionary games and computer simulations. AB - The Prisoner's Dilemma has long been considered the paradigm for studying the emergence of cooperation among selfish individuals. Because of its importance, it has been studied through computer experiments as well as in the laboratory and by analytical means. However, there are important differences between the way a system composed of many interacting elements is simulated by a digital machine and the manner in which it behaves when studied in real experiments. In some instances, these disparities can be marked enough so as to cast doubt on the implications of cellular automata-type simulations for the study of cooperation in social systems. In particular, if such a simulation imposes space-time granularity, then its ability to describe the real world may be compromised. Indeed, we show that the results of digital simulations regarding territoriality and cooperation differ greatly when time is discrete as opposed to continuous. PMID- 8356076 TI - A transmissible Creutzfeldt-Jakob disease-like agent is prevalent in the human population. AB - The etiology of most human dementias is unknown. Creutzfeldt-Jakob disease (CJD), a relatively uncommon human dementia, is caused by a transmissible virus-like agent. Molecular markers that are specific for the agent have not yet been defined. However, the infectious disease can be transmitted to rodents from both brain and infected buffy coat (blood) samples. To determine whether human CJD infections are more widespread than is apparent from the low incidence of neurological disease, we attempted to transmit CJD from buffy coat samples of 30 healthy volunteers who had no family history of dementing illness. Primary transmissions from 26 of 30 individuals produced CJD-like spongiform changes in the brains of recipient hamsters at 200-500 days postinoculation. This positive evidence of viremia was found for individuals in all age groups (20-30, 40-50, and 61-71 years old), whereas 12 negatively scored brain samples failed to produce similar changes in hamsters observed for > 900 days in the same setting. We suggest that a CJD agent endemically infects humans but only infrequently produces an infectious dementia. Disease expression is likely to be influenced by several host factors in combination with viral variants that have altered neurovirulence. PMID- 8356077 TI - Molecular regulation of human interleukin 2 and T-cell function by interleukin 4. AB - Distinct functional T-cell subsets, differing in the patterns of lymphokines produced, regulate cell-mediated and humoral immune responses. The two major types and their principal products, interleukin 4 and interferon gamma (IL-4 and IFN-gamma), are reciprocally negatively interactive. To analyze the molecular mechanism of IL-4-mediated suppression of cell-mediated immunity we studied its effects on expression of interleukin 2 (IL-2) and IFN-gamma. IL-4 pretreatment of Jurkat cells prior to stimulation resulted in a decrease in transcription of the IL2 gene. IL-4 suppressed IL-2 and IFN-gamma mRNA levels in primary human T cells, and addition of anti-CD28 antibodies relieved this suppression. Using enhancer-reporter constructs, IL-4 specifically down-regulated the NFIL-2B element. Electrophoretic mobility shift assays using a DNA oligomer containing the NFIL-2B binding site indicated that IL-4 inhibited the NFIL-2B complex and that the NFIL-2B DNA binding factor is distinct from AP-1. These results suggest that IL-4 may regulate development and function of T-cell subsets involved in cell-mediated immunity in part by inhibiting factors required for transcription of the IL2 gene. PMID- 8356078 TI - Characterization of the human CD4 gene promoter: transcription from the CD4 gene core promoter is tissue-specific and is activated by Ets proteins. AB - We analyzed the 5' transcription control sequences of the human CD4 gene. We located the transcription initiation site and showed that the CD4 core promoter (positions -40 to +16) lacks a classical "TATA" or initiator positioning consensus sequence but directs precise and efficient transcription when coupled to the ubiquitously active simian virus 40 enhancer. The transcriptional activity of the CD4 gene promoter correlated with CD4 expression in various cell types. Interestingly, the CD4 core promoter also displayed a tissue-specific transcriptional activity. Within this fragment, three nucleic acid sequences are completely conserved in the murine CD4 gene. One of these sequences contains a perfect ETS consensus sequence. Another ETS consensus sequence is located 1060 nt upstream. Electrophoretic-mobility-shift assays showed that the core promoter ETS motif binds an Ets-related protein specifically expressed at high levels in CD4+ cells. Moreover, in CD4- cells, overexpression of Ets-1 or Ets-2 efficiently and specifically activated transcription from the CD4 promoter and core promoter. These data indicate that Ets transcription factors play a central role in controlling CD4 gene expression, by binding to both a classical remote site and an unusual proximal activator sequence. PMID- 8356079 TI - Replication of UV-irradiated DNA in human cell extracts: evidence for mutagenic bypass of pyrimidine dimers. AB - We have examined the efficiency and fidelity of simian virus 40-origin-dependent replication of UV-irradiated double-stranded DNA in extracts of human cells. Using as a mutational target the alpha-complementation domain of the Escherichia coli lacZ gene in bacteriophage M13mp2 DNA, replication of undamaged DNA in HeLa cell extracts was highly accurate, whereas replication of DNA irradiated with UV light (280-320 nm) was both less efficient and less accurate. Replication was inhibited by irradiation in a dose-dependent manner. Nonetheless, covalently closed, monomer-length circular products were generated that were resistant to digestion by Dpn I, showing that they resulted from semiconservative replication. These products were incised by T4 endonuclease V, whereas the undamaged replication products were not, suggesting that pyrimidine dimers were bypassed during replication. When replicated, UV-irradiated DNA was used to transfect an E. coli alpha-complementation host strain to score mutant M13mp2 plaques, the mutant plaque frequency was substantially higher than that obtained with either unirradiated, replicated DNA, or unreplicated, UV-irradiated DNA. Both the increased mutagenicity and the inhibition of replication associated with UV irradiation were reversed by treatment of the irradiated DNA with photolyase before replication. Sequence analysis of mutants resulting from replication of UV irradiated DNA demonstrated that most mutants contained C-->T transition errors at dipyrimidine sites. A few mutants contained 1-nt frameshift errors or tandem double CC-->TT substitutions. The data are consistent with the interpretation that pyrimidine dimers are bypassed during replication by the multiprotein replication apparatus in human cell extracts and that this bypass is mutagenic primarily via misincorporation of dAMP opposite a cytosine (or uracil) in the dimer. PMID- 8356080 TI - Plasma arginine and citrulline kinetics in adults given adequate and arginine free diets. AB - The fluxes of arginine and citrulline through plasma and the rate of conversion of labeled citrulline to arginine were estimated in two pilot studies (with a total of six adult subjects) and in a dietary study with five healthy young men. These latter subjects received an L-amino acid-based diet that was arginine-rich or arginine-free each for 6 days prior to conduct, on day 7, of an 8-hr (first 3 hr, fast; final 5 hr, fed) primed continuous intravenous infusion protocol using L-[guanidino-13C]arginine, L-[5,5-2H2]citrulline, and L-[5,5,5-2H3]leucine, as tracers. A pilot study indicated that citrulline flux was about 20% higher (P < 0.05) when determined with [ureido-13C]citrulline compared with [2H2]citrulline, indicating recycling of the latter tracer. Mean citrulline fluxes were about 8-11 mumol.kg-1.hr-1 for the various metabolic/diet groups and did not differ significantly between fast and fed states or arginine-rich and arginine-free periods. Arginine fluxes (mean +/- SD) were 60.2 +/- 5.4 and 73.3 +/- 13.9 mumol.kg-1.hr-1 for fast and fed states during the arginine-rich period, respectively, and were significantly lowered (P < 0.05), by 20-40%, during the arginine-free period, especially for the fed state, where this was due largely to reduced entry of dietary arginine into plasma. The conversion of plasma citrulline to arginine approximated 5.5 mumol.kg-1.hr-1 for the various groups and also was unaffected by arginine intake. Thus, endogenous arginine synthesis is not markedly responsive to acute alterations in arginine intake in healthy adults. We propose that arginine homeostasis is achieved largely via modulating arginine intake and/or the net rate of arginine degradation. PMID- 8356081 TI - Insulin stimulates the biosynthesis of chiro-inositol-containing phospholipids in a rat fibroblast line expressing the human insulin receptor. AB - HIRc-B cells (rat fibroblasts expressing the human insulin receptor) were incubated with myo-[3H]inositol for 48 hr, and the biosynthesis of chiro [3H]inositol was investigated in the absence and presence of insulin following a time course up to 60 min. After phase separation, treatment with insulin for 15 min caused a 2.2-fold increase in the specific radioactivity of chiro [3H]inositol-containing phospholipids in contrast to a 1.2-fold increase in the specific radioactivity of myo-[3H]inositol-containing phospholipids. No insulin mediated change in the specific radioactivity was observed in the inositol phosphates or free inositols. Further detailed analysis of individual [3H]inositol-containing phospholipids demonstrated marked increases in specific activity of the chiro-[3H]inositol phospholipids after 15 min of incubation with insulin: phosphatidylinositol 4-phosphate and 4,5-bisphosphate, 4.2-fold; lysophosphatidylinositol, 1.5-fold; phosphatidylinositol, 3.2-fold. In contrast, myo-[3H]inositol-containing phospholipids demonstrated relatively small increases (1.1- to 1.4-fold) after 5 min of incubation with insulin. These findings indicate that insulin stimulates de novo synthesis of chiro-inositol-containing phospholipids at the inositol phospholipid level. PMID- 8356082 TI - Serine/threonine phosphorylation regulates binding of C hnRNP proteins to pre mRNA. AB - The C hnRNP proteins bind to nascent pre-mRNA and are thought to participate in an early step of the pre-mRNA splicing pathway. We report here that C hnRNP proteins are phosphorylated by a casein kinase II activity in a HeLa cell nuclear extract and that dephosphorylation of C hnRNP proteins is inhibited by the specific protein-serine/threonine-phosphatase 1/2A inhibitor okadaic acid. We further find that dephosphorylation of C hnRNP proteins is required for their binding to adenovirus and human beta-globin pre-mRNAs. These results indicate that the participation of C hnRNP proteins in pre-spliceosome assembly is coupled to a dynamic cycle of their phosphorylation and dephosphorylation. PMID- 8356083 TI - The N-terminal region of the 37-kDa translocated fragment of Pseudomonas exotoxin A aborts translocation by promoting its own export after microsomal membrane insertion. AB - The 37-kDa C-terminal fragment of Pseudomonas exotoxin A (PE; termed PE37 and composed of aa 280-613 of PE) translocates to the cell cytosol to cause cell death. PE37 requires a C-terminal endoplasmic reticulum retention sequence to be cytotoxic, indicating that the toxin may translocate to the cytosol from the endoplasmic reticulum. We show here that the N-terminal region of nascent PE37 can be inserted into the membrane of canine pancreatic microsomes by the preprocecropin signal sequence but then is exported or released from microsomes. The 34 N-terminal amino acids of the toxin fragment are sufficient to arrest translocation and prevent the microsomal accumulation of nascent chains that otherwise are sequestered into microsomes. These data support a role for the N terminal region of PE37 in the translocation of the toxin from the endoplasmic reticulum to the cytosol in mammalian cells. PMID- 8356084 TI - Ultrastructural localization of a neutral and basic amino acid transporter in rat kidney and intestine. AB - A sodium-independent neutral and basic amino acid transporter (NBAT) from rat kidney was recently cloned and its amino acid sequence deduced. We used light and electron microscopic immunoperoxidase labeling to determine the cellular localization of NBAT in rat kidney and small intestine. The localization was carried out using site-directed antisera raised against synthetic peptides within NBAT. The most prominent localization of NBAT was in microvilli of epithelial cells lining renal proximal tubules. Microvilli of small intestinal epithelia were less frequently immunoreactive. Unexpectedly, the most intense labeling in the small intestine was seen within enteroendocrine cells and submucosal neurons. The neuronal labeling was highly localized within dense core vesicles in axon terminals apposed to the basal lamina near fenestrated blood vessels. These results support the proposal that NBAT plays a role in reabsorption of amino acids in renal tubules. In addition, they suggest that NBAT (or NBAT-like proteins) may have multiple functions in the small intestine, including luminal uptake of amino acids and vesicular uptake of related substrates into enteroendocrine cells and enteric neurons. PMID- 8356085 TI - Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity. AB - Pathological changes of Alzheimer disease are characterized by cerebral cortical atrophy as a result of degeneration and loss of neurons. Typical histological lesions include numerous senile plaques composed of deposits of amyloid beta protein and neurofibrillary tangles consisting predominantly of ubiquitin and highly phosphorylated tau proteins. Previously, tau protein kinase I (TPK I) was purified and its cDNA was cloned. To examine the biological role of this enzyme in neurons, we have studied the induction of its kinase activity in primary cultures of embryonic rat hippocampal neurons. Treatment of cultures with amyloid beta-protein significantly increased TPK I activity and induced the appearance of tau proteins recognized by the Alz-50 monoclonal antibody. In addition, though amyloid beta-protein was neurotoxic, either cycloheximide or actinomycin D prevented neuronal death. Death was also prevented by TPK I antisense oligonucleotides but not by sense oligonucleotides. These observations suggest that rat hippocampal neurons undergo programmed cell death in response to amyloid beta-protein and that TPK I is a key enzyme in this process. PMID- 8356086 TI - Social regulation of the brain-pituitary-gonadal axis. AB - Reproduction in vertebrates is regulated by the hypothalamic-pituitary-gonadal axis via neural and hormonal feedback. This axis is also subject to exogenous influences, particularly social signals. In the African cichlid fish Haplochromis burtoni, gonadal development in males is socially regulated. A small fraction of the males, which are brightly colored, maintain territories and aggressively dominate inconspicuously colored nonterritorial males. Here we show through manipulation of the social and endocrine environment that changes in social status and gonadal state are accompanied by soma size changes in a population of gonadotropin-releasing hormone-containing neurons in the ventral forebrain. In territorial males, these cells are significantly larger than in nonterritorial males. When an animal switches from being territorial to nonterritorial through a change in social situation, these cells shrink; in animals that change from nonterritorial to territorial status, the cells enlarge. These gonadotropin releasing hormone-containing cells project to the pituitary and are ultimately responsible for regulating gonadal growth. This mechanism of socially induced cell size change provides the potential for relatively quick adaptive changes in the neuron-endocrine system without nerve cell addition or death. Since the structure of this regulatory axis is conserved among all vertebrates, other species with socially modulated reproductive physiology may exhibit a similar form of physiological regulation. PMID- 8356087 TI - Neural control of the endocrine rat heart. AB - Although atrial stretch is the accepted stimulus for atrial natriuretic factor (ANF), in vivo studies suggest a stretch-independent, neurally induced ANF release mechanism. Thus the hypothesis that cardiac nerves can stimulate ANF secretion was tested in the Langendorff-perfused, paced rat heart. Venom from the scorpion Centruroides sculpturatus was used to activate neuronal sodium channels, veratridine was added to activate sodium channels (predominantly in myocytes), and electrical stimulation was applied to the right atrial appendage. The efficacy of nerve stimulation was verified by measurements of increased neuropeptide Y in the effluent. ANF levels in the effluent increased by 120% over baseline with 0.5 microM scorpion venom and by 88% with 0.5 microM veratridine (P < 0.01). Cardiac mechanics did not explain the large, concentration-dependent ANF response to the scorpion venom, since changes in the left ventricular developed pressure were small, opposite to those induced by veratridine, and unaffected by sympathectomy or adrenergic receptor blockade. Prior chemical sympathectomy and adrenergic receptor blockade almost abolished the ANF response to scorpion venom but hardly affected the ANF response to veratridine. Addition of 1 microM tetrodotoxin abolished all ANF responses. Electrical stimulation of the atrial appendage increased the ANF secretion by 60.2% (P < 0.02), in conjunction with neuropeptide Y, whereas control stimulations were ineffective. These studies unequivocally demonstrate that stimulation of cardiac sympathetic nerves potently stimulates ANF secretion. PMID- 8356088 TI - The ornithine decarboxylase gene is a transcriptional target of c-Myc. AB - Constitutive c-myc expression suppresses cell cycle arrest, promotes entry into S phase, and results in the growth factor-independent expression of ornithine decarboxylase (ODC; EC 4.1.1.17). The ODC gene contains a conserved repeat of the Myc binding site, CACGTG, in intron 1. In this report, we demonstrate that c-Myc is a potent transactivator of ODC promoter-reporter gene constructs in fibroblasts that requires the CACGTG repeat. These sites conferred Myc responsiveness on heterologous promoter constructs, suggesting that ODC is regulated by Myc at the level of transcription initiation. Analysis of deletion and point mutants of c-myc revealed that domains required for transactivation of the ODC promoter did not include the leucine zipper of the Myc protein. This suggests that Myc may interact with transcription factors other than Max to transactivate the ODC gene. PMID- 8356089 TI - Application of physical organic chemistry to engineered mutants of proteins: Hammond postulate behavior in the transition state of protein folding. AB - Transition states in protein folding may be analyzed by linear free-energy relationships (LFERs) analogous to the Bronsted equation for changes in reactivity with changes in structure. There is an additional source of LFERs in protein folding: the perturbation of the equilibrium and rate constants by denaturants. These LFERs give a measure of the position of the transition state along the reaction coordinate. The transition state for folding/unfolding of barnase has been analyzed by both types of LFERs: changing the structure by protein engineering and perturbation by denaturants. The combination has allowed the direct monitoring of Hammond postulate behavior of the transition state on the reaction pathway. Movement of the transition state has been found and analyzed to give further details of the order of events in protein folding. PMID- 8356090 TI - Crystallization of ribozymes and small RNA motifs by a sparse matrix approach. AB - The three-dimensional structures of RNA enzymes form catalytic centers that include specific substrate binding sites. High-resolution determination of these and other RNA structures is essential for a detailed understanding of the function of RNA in biological systems. The crystal structures of only a few RNA molecules are currently known. These include tRNAs, which were produced in vivo and contained modified bases, and short oligonucleotide duplexes lacking tertiary interactions. Here we report that a number of different RNA molecules of 4-50 kDa, all synthesized in vitro, have been crystallized. A highly successful method for the growth of RNA crystals based on previously reported conditions for tRNA crystallization is presented. This method is rapid and economical, typically requiring 1.1 mg of RNA to set up an experiment and 2 weeks to complete the observations. Using this technique, we have obtained crystals of 8 of 10 different RNA molecules tested, ranging in size from a dodecamer duplex to a 208 nucleotide catalytic intron. Several of these crystal forms diffract to high resolution; in one case, we have collected a 2.8-A native data set for a 160 nucleotide domain of the group I self-splicing intron from Tetrahymena thermophila. The solution of these RNA structures should reveal aspects of tertiary structure that relate to RNA function and catalytic mechanisms. PMID- 8356091 TI - Females have a larger hippocampus than males in the brood-parasitic brown-headed cowbird. AB - Females of the brood-parasitic brown-headed cowbird (Molothrus ater) search for host nests in which to lay their eggs. Females normally return to lay a single egg from one to several days after first locating a potential host nest and lay up to 40 eggs in a breeding season. Male brown-headed cowbirds do not assist females in locating nests. We predicted that the spatial abilities required to locate and return accurately to host nests may have produced a sex difference in the size of the hippocampal complex in cowbirds, in favor of females. The size of the hippocampal complex, relative to size of the telencephalon, was found to be greater in female than in male cowbirds. No sex difference was found in two closely related nonparasitic icterines, the red-winged blackbird (Agelaius phoeniceus) and the common grackle (Quiscalus quiscula). Other differences among these species in parental care, migration, foraging, and diet are unlikely to have produced the sex difference attributed to search for host nests by female cowbirds. This is one of few indications, in any species, of greater specialization for spatial ability in females and confirms that use of space, rather than sex, breeding system, or foraging behavior per se, can influence the relative size of the hippocampus. PMID- 8356092 TI - Activation of mast cell K+ channels through multiple G protein-linked receptors. AB - The rat basophilic leukemia (RBL) mast cell line possesses cell surface receptors for adenosine whose ligation markedly potentiates antigen-driven Ca2+ influx and secretion. Here we show that engagement of these receptors and of separate P2 purinergic receptors rapidly activates an outwardly rectifying K+ conductance [GK(OR)] in RBL cells. Activation of GK(OR) by the ligands 5'-(N ethylcarboxamido)adenosine (NECA), ADP, and ATP was prevented by cytoplasmic guanosine 5'-[beta-thio]diphosphate as well as by pretreatment of the cells with pertussis toxin, implicating mediation by a G protein. Multiple cycles of induction and decay of GK(OR) were produced upon application and removal of ligand. Induction of GK(OR) by either ligand was much faster than the induction caused by guanosine 5'-[gamma-thio]triphosphate (t1/2 < 10 sec vs. 210 sec.). In control cells the maximal whole-cell conductance elicited by ADP (2.25 +/- 0.30 nS) or ATP (2.50 +/- 0.33 nS) was about twice as large as that induced by NECA (1.03 +/- 0.11 nS), and similar to that previously reported for the guanosine 5' [gamma-thio]triphosphate-elicited GK(OR) in RBL cells (2.58 +/- 1.59 nS). Treatment of RBL cells with dexamethasone upregulated Ca2+ responses to NECA, and it also nearly doubled the maximal conductance elicited by NECA without appreciable effect on responses to ADP or ATP. The failure of water-soluble second messengers to activate GK(OR) and the inability of 11 mM EGTA (< 10 nM Ca2+) to prevent activation by ADP suggest that the relevant pathway is membrane delimited. Two ion-channel blockers inhibited antigen-stimulated secretion with IC50 values similar to those at which they blocked GK(OR), suggesting that activity of the outwardly rectifying K+ channel may be important for stimulus response coupling in these cells. Potentiation of the secretory response by NECA may reflect, in part, the activation of GK(OR), which serves to repolarize the membrane more effectively than does the constitutive mechanism, thereby enhancing antigen-driven Ca2+ influx. This channel and its functionally associated receptors may allow neighboring cells of the host to modulate the response of mast cells to exogenous antigen. PMID- 8356093 TI - Two different forms of metarhodopsin II: Schiff base deprotonation precedes proton uptake and signaling state. AB - Rhodopsin is a retinal protein and a G-protein-coupled receptor; it shares with both of these families the seven helix structure. To generate the G-interacting helix-loop conformation, generally identified with the 380-nm absorbing metarhodopsin II (MII) photoproduct, the retinal Schiff base bond to the apoprotein must be deprotonated. This occurs as a key event also in the related retinal proteins, sensory rhodopsins, and the proton pump bacteriorhodopsin. In MII, proton uptake from the aqueous phase must be involved as well, since its formation increases the pH of the aqueous medium and is accelerated under acidic conditions. In the native membrane, the pH effect matches MII formation kinetically, suggesting that intramolecular and aqueous protonation changes contribute in concert to the protein transformation. We show here, however, that proton uptake, as indicated by bromocresol purple, and Schiff base deprotonation (380-nm absorption change) show different kinetics when the protein is solubilized in suitable detergents. Our data are consistent with a two-step reaction: PMID- 8356094 TI - Polymer models for interphase chromosomes. AB - The overall geometry of chromosomes in mammalian cells during interphase is analyzed. On scales larger than approximately 10(5) bp, a chromosome is modeled as a Gaussian polymer subjected to additional forces that confine it to a subvolume of the cell nucleus. An appropriate partial differential equation for the polymer Green's function leads to predictions for the average geometric length between two points on the chromosome. The model reproduces several of the experimental observations: (i) a square root dependence of average geometric distance between two marked chromosome locations on their genomic separation over genomic length scales from approximately 10(5) to approximately 10(6) bp; (ii) an approach of the geometric distance to a maximum value for still larger genomic separations of the two points; (iii) overall chromosome localization in subdomains of the cell nucleus, as suggested by fluorescent labeling of whole chromosomes and by radiobiological evidence. The model is also consistent with known properties of the 30-nm chromatin fiber. It makes a testable prediction: that for two markers a given number of base pairs apart on a given chromosome, the average geometric separation is larger if the configuration is near one end of the chromosome than if it is near the center of the chromosome. PMID- 8356095 TI - Differential expression of nerve growth factor receptors leads to altered binding affinity and neurotrophin responsiveness. AB - The low-affinity p75 neurotrophin receptor is believed to participate with the Trk receptor tyrosine kinase in the formation of high-affinity binding sites for nerve growth factor (NGF). To investigate the functional significance of the two NGF receptors, a truncated p75 receptor was stably expressed in PC12 rat pheochromocytoma cells, yielding cells with greatly reduced levels of wild-type p75 and normal Trk levels. Although these cells were capable of normal differentiation by NGF, very few high-affinity NGF binding sites were detected. These findings indicate that high-affinity binding may be functionally dissociated from biological responses. Furthermore, an increased responsiveness to neurotrophin 3 was observed, as manifested by increased neurite outgrowth. These results suggest that a correct ratio of p75 and p140trk is required to create high-affinity sites and that p75 expression may assist in the discrimination between related but different neurotrophin factors. PMID- 8356096 TI - The SCL gene product is regulated by and differentially regulates cytokine responses during myeloid leukemic cell differentiation. AB - Differentiation induction in murine M1 leukemia cells by interleukin 6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) is postulated to occur via a common receptor chain, gp130. In this study, growth factor-induced differentiation of M1 cells was accompanied by a late and persistent decrease in levels of mRNA and protein for a helix-loop-helix transcription factor, the SCL gene product. To evaluate whether reduced SCL expression was instrumental in monocyte differentiation, an SCL cDNA expression vector was introduced into M1 cells to obtain cell lines in which overexpression of SCL mRNA and protein was enforced. This resulted in a reduction in cells differentiating in response to LIF and OSM but not in response to IL-6. Scatchard analysis indicated that both parental and SCL-transfected cell lines exhibited similar receptor numbers and receptor affinities for LIF, OSM, and IL-6, suggesting that the differential responsiveness was not due to selective receptor down-modulation. Thus, these data implicate SCL in monocytic differentiation and provide evidence for differential receptor signaling pathways despite utilization of a common gp130 subunit by all three receptors. PMID- 8356097 TI - Targeted mutagenesis of DNA using triple helix-forming oligonucleotides linked to psoralen. AB - Oligonucleotides can bind as third strands of DNA in a sequence-specific manner in the major groove in homopurine/homopyrimidine stretches in duplex DNA. Here we use a 10-base triplex-forming oligonucleotide linked to a psoralen derivative at its 5' end to achieve site-specific, targeted mutagenesis in an intact, double stranded lambda phage genome. Site-specific triplex formation delivers the psoralen to the targeted site in the lambda DNA, and photoactivation of the psoralen produces adducts and thereby mutations at that site. Mutations in the targeted gene were at least 100-fold more frequent than those in a nontargeted gene, and sequence analysis of mutations in the targeted gene showed that 96% were in the targeted region and 56% were found to be the same T.A to A.T transversion precisely at the targeted base pair. The ability to reproducibly and predictably target mutations to sites in intact duplex DNA by using modified oligonucleotides may prove useful as a technique for gene therapy, as an approach to antiviral therapeutics, and as a tool for genetic engineering. PMID- 8356099 TI - Free energies for refolding of the common beta turn into the inverse-common beta turn: simulation of the role of D/L chirality. AB - Quantitative estimates of the Gibbs free-energy change (delta G) for refolding of one beta-turn conformation into another would assist rational protein design. For beta-turn models, we studied a chirally representative set of nine peptides of the form CH3CO-L1-L2-NHCH3, where loop residues L1 (i + 1) and L2 (i + 2) are achiral Gly (G), L-Ala (A), or D-Ala (a). The stabilities of their common (type I) and inverse-common (type I') beta-turn conformers (GGI is the type-I GG conformer, etc.) were estimated by free-energy simulations using explicit water molecules. An alpha-hydrogen atom of a Gly residue at L1 or L2 was replaced by a methyl group by slow growth. The resulting conformers were less stable than GGI and GGI' by about 1-3 kcal/mol (delta G = 0.9 kcal/mol for AGI and aGI', 1.0 kcal/mol for GAI and GaI', 2.1 kcal/mol for aGI and AGI', and 2.8 kcal/mol for GaI and GAI'; 1 kcal = 4.18 kJ). The delta G value for simultaneous growth of one methyl group at L1 and another at L2 was the sum of the two component delta G values. The delta G values for I-->I' refolding of the common beta-turn conformer into the inverse-common beta-turn conformer ranged over 6 kcal/mol (-3.0 for aa, 1.8 for Ga, -1.1 for aG, -0.7 for Aa, 0 for GG, 0.7 for aA, 1.1 for AG, 1.8 for GA, and 3.0 for AA). Thus, replacing L-Ala by D-Ala at both L1 and L2 of a common beta turn may contribute as much as 6 kcal/mol toward its refolding as an inverse common beta turn. PMID- 8356100 TI - Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear stress-responsive element. PMID- 8356098 TI - Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody. AB - A single-chain antibody, derived from a human monoclonal antibody that recognizes the CD4 binding region of the human immunodeficiency virus type 1 (HIV-1) envelope protein, has been designed for intracellular expression in eukaryotic cells. The single-chain antibody is composed of an immunoglobulin heavy-chain leader sequence and heavy- and light-chain variable regions that are joined by an interchain linker. The antibody is stably expressed and retained in the endoplasmic reticulum and is not toxic to the cells. The antibody binds to the envelope protein within the cell and inhibits processing of the envelope precursor and syncytia formation. The infectivity of the HIV-1 particles produced by cells that express the single-chain antibody is substantially reduced. These studies illustrate the feasibility of designing antibodies that bind and inactivate molecules intracellularly. Antibodies that act on target molecules within cells should provide a useful tool for research as well as for control of infectious and other diseases. PMID- 8356101 TI - Effects of veratridine and cocaine on the kinetics of synaptosomal dopamine release. AB - Following preloading of striatal synaptosomes with 3H-dopamine (DA), the kinetics of release have been followed for a 60-min incubation period. DA appears to be totally releasable under both depolarizing (veratridine) and nondepolarizing conditions. Cocaine has no significant effect on release under either condition. Release is consistent with a model consisting of two parallel, linear compartments (when plotted as a log function). It is proposed that the slower compartment might represent the operation of the DA transporter, while the faster compartment might represent vesicular release. PMID- 8356102 TI - Ouabain cardiotoxicity is enhanced by GABA in anesthetized rats. AB - Potential alteration of ouabain-induced cardiotoxicity by gamma-aminobutyric acid (GABA) in rats was tested by infusing ouabain for 10 min (0.7 mg/kg/min, i.v.) before or after continuous infusion of Ringer's solution with or without GABA (1 mg/min, i.v.). GABA evoked hypotension and bradycardia of similar magnitude under both conditions. The incidence of ouabain-induced ventricular fibrillation (VF) or cardiac arrest (CA) was similar in both groups. However, the time intervals to onset of VF and CA, in rats given ouabain before, but not after, GABA were shorter than in rats treated with Ringer's solution (p < 0.05). In experiments where baclofen (0.034 mg/min, i.v.) was infused after ouabain, hypotension and bradycardia occurred, but the incidence and times of ouabain-induced VF and CA were similar to control values. These results suggest that the enhancement in ouabain cardiotoxicity was mediated by GABAA receptors. PMID- 8356103 TI - Studies on the mechanism of action of colloidal bismuth subcitrate. II. Interaction with pepsin. AB - The effects of colloidal bismuth subcitrate (CBS) on porcine pepsin have been studied in vitro. CBS inhibited pepsin activity in a pH-dependent manner. CBS was not active at pH 4.0 but inhibited pepsin activity at pH 1.0 (IC50: 2.3 +/- 0.09 mmol/l) and pH 2.0 (IC50: 8.9 +/- 0.7 mmol/l). This inhibition was reversible. In the presence of the sulfhydryl ligand mercaptoethanol, which prevents precipitation of CBS, the inhibitory potency of CBS increased. CBS bound to both positively (Amberlite) and negatively charged (Dowex) ion exchangers in a pH dependent manner. With increasing acidity, binding to Amberlite increased, whereas binding to Dowex decreased. From these data we conclude that negatively charged bismuth salts derived from CBS bind at pH 2.0 and 1.0 via an ionic interaction to positively charged groups of pepsin, thereby inactivating the enzyme. PMID- 8356104 TI - Effects of chronic treatment with phenazone on the hot-plate test and [3H]serotonin binding sites in pons and cortex membranes of the rat. AB - Many reports indicate that nonsteroidal anti-inflammatory drugs exert their antinociceptive effect through adrenergic and serotoninergic systems. We investigated the acute and chronic effects of phenazone on the pain threshold and on brain serotonin binding sites. A relationship between phenazone serum levels and the antinociceptive effect was found; acute treatment with phenazone provokes a significant decrease in serotonin binding sites both in the pons and cerebral cortex after 2, 4 and 8 h, but not after 24 h. After 15 and 30 days of treatment, the number of binding sites increases both in the pons and cortex. PMID- 8356105 TI - Melatonin decreases brain serotonin release, arterial pressure and heart rate in rats. AB - The effects of intravenous administration of melatonin (30-60 mg/kg) or vehicle (10% alcohol) on arterial pressure, heart rate, blood gases or brain serotonin release were assessed in rats under urethane anesthesia. Administration of melatonin, but not the vehicle, produced a dose-related fall in mean arterial pressure, heart rate, or serotonin release in both the corpus striatum and the hypothalamus. Melatonin treatment had an insignificant effect on either PaCO2, PaO2 or pH. In addition, the melatonin-induced depressor responses were abolished by pretreatment with spinal transection, whereas melatonin-induced bradycardia was abolished by pretreatment with bilateral vagotomy. These results suggest that melatonin decreases brain serotonin release and results in sympathetic inhibition or parasympathetic stimulation which leads to hypotension and bradycardia in rats. PMID- 8356107 TI - Perceptions of acute care physical therapy practice: issues for physical therapist preparation. AB - BACKGROUND AND PURPOSE: Acute care physical therapists have experienced the effects of dramatic changes in health care reimbursement systems and population demographics. Acute care hospitals now serve a patient population of much older, chronically ill patients who are hospitalized for shorter periods of time in a practice environment in which physical therapy staffing resources are often inadequate. The purposes of this study were to document common experiences in the practice of acute care physical therapy and to identify differences in the perceptions of physical therapists with varying levels of experience and in various sizes of acute care facilities. SUBJECTS AND METHODS: A survey questionnaire was mailed to 500 randomly selected physical therapists employed in acute care facilities. The therapists answered questions regarding the frequency of various physical therapy evaluation and treatment practices, problems encountered in delivering physical therapy services, coordination of the discharge planning process, and perceptions of staffing trends in the acute care setting. The responses of 188 physical therapists who completed the survey were compared by their experience levels and the size of the institutions in which they practiced. RESULTS: Subjects reported that patient factors, such as medical complications and cooperation; organizational factors, such as staffing shortages and large caseloads; and health care system constraints, such as difficulty changing orders and limited time in which to work with the patient interfered with patients reaching physical therapy goals. CONCLUSION AND DISCUSSION: Inadequate skills for successful acute care practice and maladaptive therapist beliefs about acute care career possibilities may adversely affect physical therapist career longevity in the acute care setting. PMID- 8356106 TI - Diagnosis and treatment in physical therapy: an investigation of their relationship. AB - BACKGROUND AND PURPOSE: The diagnosis made by a physical therapist gives direction to the selection of therapeutic interventions. Therefore, in an investigation, specific relationships between diagnoses and therapeutic interventions are expected. This study was designed to test whether such relationships exist. SUBJECTS AND METHODS: Data on diagnosis, treatment goals, and interventions were gathered on 8,714 patients by 74 physical therapists. The diagnosis and treatment goals were defined in terms of impairments and disabilities. RESULTS: Specific relationships were found to exist between those impairments and disabilities that were chosen as a basis for forming treatment goals and the application of interventions. These relationships are particularly marked at the impairment level. CONCLUSION AND DISCUSSION: It is concluded that the diagnostic categories validly predict which interventions are applied and that the selection of interventions depends on which treatment goals are pursued. PMID- 8356108 TI - Test-retest reliability of two tiltboard tests in children. AB - BACKGROUND AND PURPOSE: Most clinical evaluations of postural control in children are relatively subjective and have not been tested for reliability of scoring. The purpose of this study was to investigate the test-retest reliability of measurements obtained with two tiltboard tests. SUBJECTS: Subjects were 18 children, aged 53 to 81 months (mean = 64.4, SD = 8.3), who were typically developing (TD group) and 18 children, aged 50 to 79 months (mean = 63.3, SD = 8.4), with developmental delays (DD group). METHODS: Each child was tested using the two tilt-board tests and was then retested using the same tests approximately 1 week later. The maximum angle of tiltboard tilt prior to any postural adjustment by the child was recorded. RESULTS: Intraclass correlation coefficients for test-retest reliability (two-way, random-effects, repeated measures model) ranged from .49 to .54 for the TD group and from .52 to .82 for the DD group. Angles were higher for both groups for the second test. CONCLUSION AND DISCUSSION: The results suggest that these tiltboard tests do not give stable and reliable measurements across test sessions. Before these tests can be used to document change in postural control abilities across time, further research is warranted. PMID- 8356110 TI - APTA policy. PMID- 8356109 TI - Intrasubject reliability of spinal range of motion and velocity determined by video motion analysis. AB - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the repeatability of spinal range of motion (ROM) and movement velocity measurements of patients with chronic low back pain, using a two-dimensional motion analysis system. This apparatus uses reflective markers placed on anatomical landmarks and video digitization to derive ROM measurements from three segments of the spine and associated velocities through the respective ROMs. SUBJECTS: Forty-two patients with chronic LBP underwent ROM and movement velocity testing. METHODS: Each subject was tested twice without removal of the markers to minimize error contribution from differences in marker placement. RESULTS: Results indicated that both the ROM measures and the velocity measures were highly repeatable. Intraclass correlations for the ROM measures ranged from .77 to .96. Velocity measures were also reliable, with intraclass correlation coefficients ranging from .75 to .97. CONCLUSION AND DISCUSSION: Overall, the results seem to indicate that the video motion analysis system used in this study yields repeatable ROM and velocity measures on a clinical population. In practice, however, the measures may reflect greater errors due to the need of examiners to relocate markers at different testing sessions. These systems also offer distinct advantages over other means of obtaining ROM and velocity measures. The results of this study indicate that these measures may be obtained without undue concern for measurement artifact due to the instrumentation reliability. PMID- 8356111 TI - Continuing education rating system needed. PMID- 8356112 TI - RepFIB: a basic replicon of large plasmids. AB - The distribution of the RepFIB replicon among a total of 20 plasmid incompatibility groups was determined using Southern blot and polymerase chain reaction analysis. The presence of the replicon was confirmed in 25 of 55 plasmids tested. The majority of plasmids carrying RepFIB are from the IncF incompatibility groups, but one plasmid from IncI and one plasmid from IncP also possess the replicon. Seven different examples of RepFIB were sequenced in the minimal replicon region to obtain 1525 bp of sequence information covering the repA gene and flanking repeat regions for comparison. An analysis of these sequences plus three sequences previously reported showed almost perfect conservation of the predicted protein sequence of RepA and of the flanking DNA repeats. DNA sequence data were analyzed using maximum parsimony techniques to describe the possible evolutionary relationships of the 10 examples of RepFIB. PMID- 8356113 TI - Transcription of the kalilo linear senescence plasmid from Neurospora intermedia. AB - The 8.6-kb kalilo linear mitochondrial plasmid of Neurospora intermedia was found to give rise to multiple transcripts of 8.6, 4.4, 4.0, 1.3, 1.2, and 0.9 kb. Plasmid transcripts were found in all the developmental stages tested and were present in cells with and without plasmid integration into mtDNA. The 4.4- and 4.0-kb transcripts corresponded to the two known ORFs in size, position, and polarity. An analysis of RNA fractions has confirmed the mitochondrial location of kalilo. The kalilo-specific RNA appears to be selectively unstable in affected strains of N. intermedia; this may be a general property of linear plasmid RNA. Transcripts are most likely initiated from near the termini of the linear plasmid. Primer extension and sequencing showed a clear 5' RNA end at nucleotide 101. However, the sequence in this region does not show homology with any known mitochondrial, plasmid, or nuclear promoter. The sequence does show homology with the tip of the plasmid and marks the border of a long series of direct repeats. Possibly the plasmid RNA polymerase may be bifunctional, recognizing sequences at the plasmid tip as well as the promoter. PMID- 8356114 TI - Optimization of methods for transfecting Spiroplasma citri strain R8A2 HP with the spiroplasma virus SpV1 replicative form. AB - Seven methods for the transfection of bacteria were compared and optimized for use in Spiroplasma citri strain HP using the spiroplasma virus SpV1 R8A2 B replicative form (RF). These methods included both chemical-mediated protocols [CaCl2, RbCl/CaCl2, polyethylene glycol (PEG)], liposome-mediated transfection, electroporation, freeze/thaw cycling, and natural competence. The best protocols were those which utilized PEG or electroporation, yielding transfection frequencies of 1.4 x 10(-4) and 9.1 x 10(-4) transfectants/colony-forming unit (CFU), respectively. For both of these protocols, transfection frequencies were higher using CsCl-purified, covalently closed, circular DNA. In the PEG-mediated protocol, Sigma 8000 brand PEG at a final concentration of 44%, and the presence of carrier DNA proved to be optimal with a PEG exposure time of 2 min. Using electroporation, a 1-2 ms pulse of a 6.5 kV/cm electric field was best; washing the host cell pellet prior to electroporation enhanced efficiencies by 50%. Linearization of the DNA resulted in lower transfection efficiencies by either method. PMID- 8356115 TI - Genetic organization and evolution of the cryptic plasmid of Neisseria gonorrhoeae. AB - Three promoters have been identified on the phenotypically cryptic plasmid of Neisseria gonorrhoeae that can direct transcription in Escherichia coli. These promoters do not seem to function at a detectable level when N. gonorrhoeae is grown in vitro under normal growth conditions. The T7 RNA polymerase expression system has been used to identify the proteins encoded by this plasmid, and a series of subclones were constructed and used to localize the gene encoding each protein. In a search of the sequence databases, we have discovered that the derived amino acid sequence of a 1.2-kb segment of the plasmid shows a high degree of sequence similarity to the Mob proteins encoded by the colicinogenic plasmids ColA, ColE1, and ColK of E. coli. The 1.2-kb segment contains part of a Col mobilization region that has subsequently been inactivated by a small duplication. During the recombination event that formed the cryptic plasmid one of the mobilization genes was fused to a cryptic plasmid open reading frame to form the cppB gene. Despite the manner in which it was formed, we have shown that the cppB gene can be expressed when N. gonorrhoeae is grown under the appropriate environmental conditions. PMID- 8356116 TI - A natural A/T-rich sequence from the yeast FBP1 gene exists as a cruciform in Escherichia coli cells. AB - Palindromic or semipalindromic sequences can adopt cruciform structures in DNA in vitro. It has been demonstrated in some cases that A/T-rich cruciforms exist also in vivo in Escherichia coli. The biological function of those structures is not understood although putative cruciforms have been found in interesting locations on replication origins, operators, or transcriptional termination regions. Here we show by means of the use of structure-dependent nucleases that the 3' end of the yeast FBP1 gene contains a stable cruciform both in vitro and in E. coli cells and that in both cases, its extrusion depends on the DNA supercoiling state. PMID- 8356117 TI - Clostridium perfringens-Escherichia coli shuttle vectors that carry single antibiotic resistance determinants. AB - Two versatile Clostridium perfringens-Escherichia coli shuttle vectors were constructed. Each plasmid carried a single antibiotic resistance gene which was expressed in both organisms. The plasmid pJIR750 encoded resistance to chloramphenicol and pJIR751 encoded resistance to erythromycin. Each plasmid contained the pUC18-derived multiple cloning site and the lacZ' gene which enabled direct screening for recombinants in E. coli. These plasmids should prove invaluable for the genetic manipulation of C. perfringens. PMID- 8356119 TI - Refinements using free-tissue transfer for complex cranial base reconstruction. AB - Resection of skull base tumors may sometimes result in massive extirpation defects that are not amenable to local tissue closure. Closure of large basicranial defects can be performed with either a myocutaneous, a deepithelialized myocutaneous, or a simple muscle free flap designed from the ample rectus abdominis vascular territory. This free-tissue donor site has abundant and reliable well-vascularized tissue that can easily be customized to seal these tenuous areas. The rectus abdominis muscle and its vascularized territory were used in 18 of 19 consecutive patients at our center to close basicranial ablation defects. Of these, 6 were rectus abdominis muscle flaps, 5 were myocutaneous rectus abdominis flaps, and 7 were deepithelialized rectus abdominis muscle flaps. All free flaps survived. The intracranial space was sealed successfully in all but one patient. This patient underwent reconstruction with a muscle free flap and had a postoperative cerebrospinal fluid leak. This complication could have been avoided by using a deepithelialized myocutaneous flap to obliterate the central dead space with the vascularized subcutaneous fat. Two patients experienced minor wound infections, and one had a subdural abscess that was fully contained by a free flap placed over the duraplasty. One patient had a donor-site hernia. There was no incidence of meningitis. Knowledge of the anatomy of the vascular territory of the deep inferior epigastric vessels can be used judiciously to secure three-dimensional reconstruction of the skull base. The donor site supplies ample tissue for reconstruction and allows individual tailoring for obliteration of geometrically complex extirpation defects in and around the cranial base without the need to reposition the patient. PMID- 8356118 TI - Overproduction and purification of the colicin E1 immunity protein. AB - Colicin E1 immunity protein encoded by the plasmid colicin E1 was overproduced in Escherichia coli from an expression plasmid which was constructed by placing the immunity protein-encoding sequence downstream of the tac promoter and by properly positioning the ribosome binding site on a run-away replication vector. The immunity protein was solubilized with 0.5% Brij 58 from the membrane fraction and purified to homogeneity by a simple batch procedure with hydroxyapatite gel and reverse-phase chromatography. A 15-residue NH2-terminal amino acid sequence was determined to be the same as that deduced from the DNA sequence. The effect of the purified immunity protein on membranes was tested in vitro using solute loaded liposomes. The immunity protein added to the liposomes showed a small but significant channel or lytic activity that is an indicator of its hydrophobic nature. PMID- 8356120 TI - Computer-assisted three-dimensional planning in craniofacial surgery. AB - Three-dimensional surface reconstruction from computed tomographic (CT) data has been used to plan craniofacial operations. Cephalometric and anthropometric databases were integrated with three-dimensional CT reconstructions to quantitate the skeletal deformity and to assist in the design of the surgical procedure. Interactive techniques were developed to simulate osteotomies and skeletal movements in three dimensions on the computer-generated surface images. The ocular globes were referenced to position the orbital segments; i.e., the osteotomized segments were transposed into normal anatomic relationship with respect to the eyes. The measurements from the computer graphic simulation were used intraoperatively to establish the correct position of the skeletal segments. PMID- 8356121 TI - [Measurement of normal eyeball position and its application for evaluation of exophthalmos in craniofacial synostosis]. AB - The chronologic changes in eyeball position in relation to bony landmarks were studied by CT scans. The results were applied to the preoperative evaluation in 16 craniofacial synostosis patients. Ten subjects from each age group were selected from more than 2000 subjects who underwent CT scanning of the skull without any brain and skull diseases. These age groups ranged from birth to 20 years of age. The following four distances were measured on the CT section incorporating lenses: (1) the distance from the dorsum sellae to the lenses, (2) the distance between the lateral orbital rim and the lenses, (3) the distance from the nasal root to the lenses, and (4) the width between the lenses. These distances also were measured in 16 craniofacial synostosis patients preoperatively, and the results were compared with those of the healthy individuals in the same age group. The distances of the lenses from the nasal root and from the lateral orbital rim were larger than in the healthy individuals in almost all craniofacial synostosis patients. However, the distance from the dorsum sellae to lenses was the same as that in healthy individuals on the whole. PMID- 8356122 TI - Nasopharyngeal profile and velopharyngeal valve mechanism. AB - Proper management of velopharyngeal insufficiency requires an understanding of normal velopharyngeal anatomy and function. The present cephalometric study correlates the nasopharyngeal profile at rest with velopharyngeal function as observed by nasendoscopy and fluorographic and videofluoroscopic studies. Fifty two normal individuals and 23 patients with insufficient velopharyngeal valves were examined. A correlation was found between nasopharyngeal profiles at rest and the closure patterns of the velopharyngeal valve. It was found that when existent, Passavant's ridge is subsequently formed where thick soft tissue corresponding to the superior constrictor muscle is found beneath the mucosa of the posterior pharyngeal wall at rest. Our conclusion is that Passavant's ridge is formed by the superior constrictor. The present study represents additional confirmation that differences in velopharyngeal closure patterns are the result of differences in anatomy. A biomechanical model of velopharyngeal valving is presented based on individual spatial muscular orientation and the hierarchical recruitment of the velopharyngeal muscles. This recruitment is progressive and is dependent on the effort required to achieve tighter velopharyngeal sealing. PMID- 8356123 TI - The split-lip advancement technique (SLAT) for the treatment of congenital sinuses of the lower lip. AB - In this paper we present 7 cases of Van der Woude syndrome and describe a new surgical technique for the treatment of congenital sinuses of the lower lip. Our technique is essentially a new modification of the elastic lip flap technique of Goldstein. We term this procedure the split-lip advancement technique, in which two opposite labial artery--based flaps including the whole thickness of the vermilion and the mucosal surface of the lip are used to repair the median defect that resulted from excision of the sinuses. To our knowledge, there have been no reports of the use of this technique in the treatment of congenital sinuses of the lower lip. PMID- 8356124 TI - A method of treatment of constricted ears with a conchal cartilage graft to the posterior auricular plane. AB - In order to make natural auricular features in a simple and certain way and also to prevent the occurrence of a postoperative lop-eared deformity, we contrived a new method to treat constricted ears. Our method consists of correction of the anthelical deformity according to a modified Converse method and a cartilage graft harvested from the posterior region of the concha to fix as a support on the posterior auricular plane which enables the auricle to maintain a normal shape. This method resulted in very satisfactory treatment of prominent ears or ears with mild helical constriction, categorized as group I, IIa, or IIb on Tanzer's classification, and the patients did not have marked postoperative problems. Thus, in this respect, our technique is considered to be a very effective and safe method. PMID- 8356125 TI - Recipient vessels in head and neck microsurgery: radiation effect and vessel access. AB - Historical cohort analysis compared free-flap survival rates in 226 irradiated and 108 nonirradiated head and neck reconstructions. The failure rate for the irradiated flaps (3.5 percent) did not differ significantly from that for the nonirradiated group (2.9 percent). A case-control study of the failed irradiated flaps revealed infection and lag time between radiotherapy and surgery as the only factors significantly associated with free flap failure. Salvage techniques (vein grafting, cephalic transposition, and Corlett looping) for recruiting recipient vessels into radically ablated head and neck beds are reviewed. PMID- 8356127 TI - Face lift without preauricular scars. AB - A subperiosteal rhytidectomy is described that corrects aging of the forehead, the orbital region, the nasolabial fold, and the cheeks. It substantially improves muscular tone, consistency of subcutaneous tissue, and projection of malar volume. Its use with proper preoperative evaluation of the grade of facial aging reduces the indication for preauricular incision. PMID- 8356126 TI - Frostbite in the prairies: a 12-year review. AB - A 12-year retrospective review of inpatient frostbite injury was undertaken in three tertiary hospitals serving a northern prairie population of 650,000. In the 125 patients identified, the mean age was 41 years, with a range of 3 to 90 years. Predisposing factors were alcohol consumption (46 percent), psychiatric illness (17 percent), vehicular trauma (19 percent), vehicular failure (15 percent), and drug use (4 percent). Profound hypothermia with a core temperature less than 32 degrees C was present in 12 percent. Anatomic distribution was 19 percent upper extremity, 47 percent lower extremity, 31 percent combined upper and lower extremity, and 3 percent facial or trunk only. Factors correlating with amputation of parts (p < 0.05) were duration of exposure, lack of proper attire, remote site of injury, presence of wound infection, and delay in seeking treatment. Prophylactic systemic antibiotics did not decrease the incidence of wound infection. Comparison with nine other civilian series revealed striking similarities in the patient populations. PMID- 8356128 TI - Causes for cancellation of aesthetic and reconstructive procedures. AB - Cancellation of plastic surgical procedures has several deleterious effects, including emotional distress and economic ramifications. This prospective study, conducted over a 12-month period in a solo practice, reviewed the factors that contributed to surgical cancellations. Cancellations occurred despite many strict measures such as at least two preoperative visits, in-depth counseling and reinforcement by surgeon and staff, laboratory testing done 2 weeks prior to surgery, detailed evaluation of medical background, extensive written and verbal instructions to avoid medications that adversely affect surgery, and thorough discussion of payment plans and insurance coverage, including predetermination of any third-party coverage. Of the 952 patients (667 males, 285 females) scheduled for surgery, 113 experienced cancellation of the operation, either by the surgeon and staff or by the patient. Cancellations were proportionally fewer in male patients (p < 0.025). The total number of scheduled procedures was 1590 (some patients scheduled for more than one procedure); 727 of these were cosmetic (46 percent), and 863 were reconstructive (54 percent). Of the 205 procedures canceled, cosmetic procedures were more likely to be canceled (p < 0.001), since 123 (16.9 percent) cosmetic procedures were canceled in contrast to 82 (9.5 percent) canceled reconstructive procedures. Because of multiple cancellations, there were a total of 119 cancellations for 113 patients. Thirty of the 113 patients were rescheduled at a later date. Of these 30, 24 did undergo surgery, while 6 canceled for a second time. Thirty-two of the 113 canceled patients (28.3 percent) were patients in their fifth decade of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356129 TI - A one-stage nipple reconstruction with the "modified star" flap and immediate tattoo: a review of 100 cases. AB - Nipple reconstruction employing both grafts and local flaps has historically been a staged procedure. This paper presents a one-stage procedure using a local flap with immediate tattoo that has the advantages of high patient satisfaction and low cost. The procedure can be performed in a minor surgery suite with local or no anesthetic in 15 to 30 minutes. In this series of 100 nipples there has been only one partial necrosis, which was easily corrected with a "boost" procedure. Only 8 percent of patients required revision procedures in the office, and there have been no infections or wound complications. Patient satisfaction and compliance have been excellent because the procedure is fast and easy with minimal morbidity. Modifications in technique are presented, based on the type of breast reconstruction (implant versus flap), local scarring, and size and color of the opposite nipple-areola complex. PMID- 8356130 TI - Definitive diagnosis of breast implant rupture using magnetic resonance imaging. AB - Breast implant rupture is an important complication of augmented and reconstructed breasts. Although several techniques such as mammography, xeromammography, ultrasound, thermography, and computed tomographic (CT) scanning have been proven to be useful to detect implant rupture, they have several disadvantages and lack specificity. In the current study, we have established magnetic resonance imaging (MRI) as a definitive, reliable, and reproducible technique to diagnose both intracapsular and extracapsular ruptures. The study was conducted in 100 symptomatic patients. Our imaging parameters were able to identify ruptures in implants with silicone shells. All the ruptures showed the presence of wavy lines, free-floating silicone shell within the gel ("free floating loose-thread sign" or "linguine sign"). We had a 3.75 percent incidence of false-positive and false-negative results. The sensitivity for detection of silicone implant rupture was 76 percent, with a specificity of 97 percent. In addition, we also were able to identify the artifacts that may interfere with the definitive diagnosis of implant rupture. PMID- 8356131 TI - The role of microvascular surgery in limb-sparing procedures for malignant tumors of the knee. AB - Limb-sparing surgery has proven to be a feasible alternative to amputation for treatment of malignant tumors about the knee. Microvascular surgery and the possibility of providing healthy, stable soft-tissue coverage to the affected limb have expanded the possible role of limb-sparing techniques. Microvascular free flaps were utilized in 26 patients undergoing resection for large malignant tumors of the knee or adjacent to the knee. Patients were then followed for a minimum of 3 years to a maximum of 7 years and evaluated for tumor recurrence and limb function. Survival and disease-free interval were 68 and 77 percent, respectively, in stage II patients and only 50 and 0 percent, respectively, in stage III patients. Function, as determined by the MSTS functional evaluation system, was found to be fair to good in all patients. Microvascular free-tissue transfer has proven to be a valuable adjunct in limb-sparing surgery. PMID- 8356132 TI - Application of maxillofacial miniplating and microplating systems to the hand. AB - During the past several years, a profound change in our approach to bone stabilization in the hand has occurred. Today, standard management of almost any fracture requiring open reduction as well as most arthrodeses and osteotomies will incorporate rigid fixation employing one of the maxillofacial systems. Many of the early concerns, such as increased complexity of the procedure, the need for extensive periosteal stripping, bulkiness of the plates (with potential palpation, tenderness, and the impingement on tendon and joint motion), and the anticipated frequent need for removal, have been allayed. Thinner plates, the smallest screws from the miniplating systems, and the introduction of the microplating systems (Luhr and Synthes) have obviated much of the anticipated difficulty with tendon gliding and have made the necessity for subsequent plate removal a rarity in our practice. The use of these systems allows much earlier mobilization postoperatively, reducing the incidence of joint stiffness and tendon adhesion. This paper discusses our series of 143 patients (average follow up time over 18 months) and the application of miniplating and microplating systems for a variety of fractures, osteotomies, and arthrodeses in the hand. PMID- 8356133 TI - Histomorphologic changes in expanded skeletal muscle in rats. AB - Tissue expansion is one of the powerful tools for various reconstructive procedures and has proven to provide more available local tissues. However, limited attention has been given to the characteristics of expanded skeletal muscle. Using a rat model (n = 41), we expanded the rat gracilis muscle and investigated the histomorphologic changes in the expanded skeletal muscle. By expansion, the gracilis muscle after 3 weeks increased 50.4 to 58.4 percent in length and 60.5 percent in width and decreased 39.0 to 42.0 percent in thickness. Histologically, the expanded muscle demonstrated a normal striation and no signs of inflammation or necrosis. The cross-sectional areas of muscle fibers indicated that expanded muscle consisted of predominantly smaller fibers. Vasculature in the expanded muscle demonstrated a longer network of arteries and a more obvious and developed arterial arcade. The average number of sarcomeres in a fiber estimated from the sarcomere length and fiber length was significantly greater (46.5 percent) in the expanded muscle. These findings suggest that the expansion of skeletal muscle is not a "stretching" process of muscle but rather a growth process of the muscle accompanied by an increase in the number of sarcomeres per fiber. Furthermore, the expanded skeletal muscle appears to preserve normal skeletal muscle architecture, vasculature, and function while undergoing the ischemic stress of expansion. PMID- 8356134 TI - Cross-chest C7 nerve grafting followed by free muscle transplantations for the treatment of total avulsed brachial plexus injuries: a preliminary report. AB - The number of donor nerves available for nerve transfer in the reconstruction of total root avulsion injuries of the brachial plexus is always insufficient. Use of the contralateral normal C7 cervical nerve as a donor nerve is a new approach to obtain more nerve fibers but also is a controversial procedure. Fifteen patients with total root avulsion of the brachial plexus received cross-chest C7 nerve grafting as the first stage of reconstruction. Eight of these patients, after an interval of 11 to 20 months, had free muscle transplantations (one to three muscles transferred per individual) to the affected limb. A long period of rehabilitation (at least 2 years) is required. The donor limbs of the 15 patients showed negligible deficits of motor and sensory function. Although independent movement of the transferred muscles from the contralateral limb has not been achieved, useful function of the reconstructed limb is possible. The preliminary results are encouraging. PMID- 8356135 TI - Reinnervation of denervated Pacinian corpuscles: ultrastructural observations in rats following free nerve grafts. AB - Nerve transection and immediate free nerve grafts using rat sciatic nerves were employed to observe the morphologic changes in periodical denervation and reinnervation of Pacinian corpuscles located on the interosseous membrane between the fibula and tibia. During periods of from 2 weeks to 20 months after the surgery, a total of 28 corpuscles were obtained under an operating microscope and processed for morphologic analysis using light and electron microscopes. Based on our morphologic findings, normal corpuscles were composed of an axon terminal and inner and outer cores. The axon terminal disappeared within 2 weeks after the nerve grafts, but the original inner and outer core cells remained for up to 20 months. In addition, a small number of collagen fibrils was observed between the inner and outer core cells. After 4 months, multiple axon terminals began to regenerate in the inner core. From 7 to 20 months, these axon terminals in some corpuscles developed a structure resembling that of normal terminals. Some of these terminals were located in the center of the inner core, but a few were in contact with the outside of the inner core. The production of collagen fibrils in denervated corpuscles was periodically activated in the intercellular spaces. These findings suggest that the morphologic changes in denervated corpuscles correspond to those in denervated nerves. Inner core cells, which are continuous with Schwann cells, remain in their original condition in denervated corpuscles until regenerating nerves enter the inner core and are essential for corpuscle regeneration, because they may produce some trophic substances that induce the regeneration of multiple axon terminals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356136 TI - Chest-wall reconstruction for spondylocostal dysostosis. AB - A child with respiratory insufficiency due to a lethal syndrome known as spondylocostal dysostosis is described. Severe chest-wall deformities with resultant paradoxical chest-wall motion were successfully corrected by surgical reconstruction of the right thorax. We conclude that patients with the severe lethal form of the syndrome may benefit from aggressive surgical correction of the thoracic abnormality. PMID- 8356137 TI - Advances in cosmetic micropigmentation. AB - Cosmetic micropigmentation for implanting pigments into the skin is a relatively new and beneficial procedure. We have found patient satisfaction to be high and complication rate low. We do stress that the help of an aesthetician is necessary in determining the color of pigmentation. PMID- 8356138 TI - Reversed cephalic vein: a lifeboat in head and neck free-flap reconstruction. AB - Free flaps always followed surgical resection in head and neck cancer patients as a means of reconstruction. Problems may be encountered in recurrent patients who have received postoperative cervical irradiation, since finding a good, healthy vein for microanastomosis is sometimes difficult. The internal jugular vein, with or without vein grafting, as the recipient vessel may solve the problem. However, we encountered two patients in whom the internal jugular vein was very fibrotic as a result of irradiation. A long vein graft to the nonirradiated, healthy area was the only choice in this condition. A new method in which a reversed cephalic vein is used as the recipient vessel was designed. It seems that the reversed cephalic vein can play the role of lifeboat as recipient vein and solve the most difficult problem encountered in head and neck free-flap surgery. PMID- 8356139 TI - "Iris" technique for immediate umbilical reconstruction. PMID- 8356140 TI - Extended transverse rectus abdominis musculocutaneous flap. AB - The transverse rectus abdominis musculocutaneous flap is widely used for breast reconstruction, but it does not have a rich blood supply. A previous article described the inclusion of superficial epigastric vessels and superficial circumflex iliac vessels to "supercharge" the flap. Subsequent experience has shown that the external pudendal vessels also can be used for "supercharging." PMID- 8356141 TI - Presternal bronchogenic cyst in an adult. PMID- 8356142 TI - Kaposi sarcoma limited to the glans penis. PMID- 8356143 TI - Lip augmentation. PMID- 8356144 TI - Thyroid "storm" after cervical facial rhytidectomy. PMID- 8356145 TI - Treatment for trichiasis. PMID- 8356146 TI - Repair of anterior tibial muscle hernia. PMID- 8356147 TI - American center for plastic and reconstructive surgery through the eyes of a surgeon from Russia. PMID- 8356148 TI - Where to use superficial lipoplasty (liposuction)? PMID- 8356149 TI - Reports in the media on breast implants. PMID- 8356150 TI - Possible hemorrhage after inferior turbinectomy. PMID- 8356151 TI - Prevention of violence. AB - Primary care physicians can easily incorporate efforts toward the primary and secondary prevention of family violence into their practices. By designing a preventive effort using the phases of the family life cycle, a developmentally appropriate system of prevention is created. The anticipatory guidance at each (annual) visit acknowledges family transitions and assures the family that abuse is a health issue and that the physician is a resource for issues of violence prevention. Using the FLC, the first phase is Coupling, when there is a risk of partner violence that continues as long as there is a partnership. Pregnancy and childbirth bring concerns of child neglect and battery. Older children are at additional risk for child sexual abuse. As families age, risks develop for elder abuse, too. The regular discussion of these issues raises the awareness that the potential for family violence continues over the life span and allows the physician opportunities to assess the risk of violence in that family and make appropriate preventive referrals. Primary care physicians are optimally positioned to address violence and its prevention in the office: they know and care for family units over time. Physicians are respected and trusted advisors who can become effective in preventing violence. PMID- 8356152 TI - Domestic violence. AB - Domestic violence is an enormous health care issue that primary care physicians are powerfully suited to address. Rarely, however, do primary care physicians recognize that many of the patients who regularly and routinely present to them are victims of abuse. This article is designed to empower America's front-line doctors to recognize and appropriately treat the many victims of domestic violence who currently suffer from this silent epidemic. The reader will come to understand that it is via relatively simple-to-learn techniques that physicians can significantly impact the health and well-being of their communities. PMID- 8356153 TI - Psychological child maltreatment. A developmental view. AB - This article explores the concept of psychological child maltreatment. It begins with a definition of psychological maltreatment in terms of care-giver behavior that thwarts the meeting of the needs of children. It focuses on five forms of psychological maltreatment that are of concern to the practitioner: rejecting (sending messages of rejection to the child), ignoring (being psychologically unavailable to the child), terrorizing (using intense fear as a weapon against the child), isolating (cutting the child off from normal social relationships), and corrupting (missocializing the child into self-destructive and antisocial patterns of behavior). PMID- 8356154 TI - Child physical abuse. AB - Child abuse is an age-old problem for which we have had documentary records for as long as we have had recorded history. This article reviews the ethical dilemmas, diagnosis, interviewing guidelines, physical examination, and treatment for child physical abuse. Also discussed are unusual manifestations and differential diagnosis. PMID- 8356155 TI - Initial evaluation and interview techniques for child sexual abuse. AB - Because physicians are often the first professionals to have contact with a sexually abused child, they must be alert to the symptoms and prepared to respond knowledgeably. Early and effective intervention affects the overall prognosis for the child and family positively. As physicians become aware of child sexual abuse, protocols can be used routinely as part of a child's medical care. Regular checks on potentially abusive situations can prevent the tragic and traumatic occurrence of child sexual abuse. PMID- 8356156 TI - Medical evaluation of the sexually abused child. AB - Clearly, there are numerous troubling variations in the medical diagnosis of child sexual abuse. These variations include delays in disclosure; rapid healing; maturational changes; variations in normal congenital findings; the technique of the examiner; patient position, relaxation, and cooperation; and additional medical conditions that mimic abuse. For these reasons, physical evidence is often inconclusive and can be an unreliable source of information in child sexual abuse cases. The reader is logically cautioned against attempts to diagnose child sexual abuse based on a single finding, particularly that of the diameter of the hymenal orifice. Emphasis on the child's history in documenting the abuse is increasing. As physicians, we must develop interviewing techniques that will assist in child protection, and we must listen and believe the comments made by our patients. PMID- 8356157 TI - Treatment of child abuse. AB - Standards of care have recently been established for the diagnosis and treatment of child abuse. This article addresses the key areas of treatment with which each primary care physician should be acquainted. As part of a community-based approach to this problem, the physician can positively impact the prognosis for the victimized child and his or her family. PMID- 8356158 TI - Elder abuse. AB - Elder abuse is a tragedy both for the individual and for society because it occupies a pivotal position in the family life cycle of violence. Great variety exists among victims, abusers, and situations; thus, no single model is adequate to explain cause and direct treatment. Primary care physicians must be alert to the possibility of elder abuse in their patients and aware of resources within their community for managing cases once identified. Federal laws and regulations must take a proactive, long-term approach to the solution of this problem and must respect the autonomy of competent elderly patients. PMID- 8356159 TI - Survivors of abuse. Health care issues. AB - This article has discussed the most common sequelae of victimization with regard to incest, rape, and battering. Although legislators and law-enforcement officials have traditionally been viewed as having primary responsibility for the prevention and control of violence, it is now known that physicians must also act in this regard. Their action is especially required with regard to victim assessment and treatment. Physicians serve as the entry points not only to the health care system, but also to other resources for victims of violence. By identifying their victimized patients and by understanding the antecedents of their patients' symptoms, physicians can go much further in meeting their patients' needs for physical, mental, and social well-being. Given the scope and impact of violence, physicians have a moral and ethical obligation to inquire about the possibility of current violence, past violence, or both in their patients' lives. PMID- 8356160 TI - Legal considerations in cases of child abuse. AB - Child abuse is a common pediatric problem that can be recognized and treated appropriately by all primary care physicians who care for children. One of the necessary skills in this process involves being prepared to interface with the legal system. The physician is mandated to report suspected child abuse according to his or her state laws. He or she must be aware of the legal recourses for child protection in cases when the child remains at risk. When interacting with the child, a number of legal considerations can guide the physician in obtaining information with history, physical examination, and specimen collection. Finally, the physician may be called to testify. An understanding of how to prepare for court and how to conduct oneself in court is the final necessary skill for the primary care physician who sees children. This article provides the primary care physician with a practical understanding of the legal considerations in child abuse. PMID- 8356161 TI - The biologic basis of posttraumatic stress. AB - The psychological effects of trauma are accompanied by biologic changes in the stress response that persist when people develop posttraumatic stress disorder (PTSD). This article explores the nature of this altered stress response; provides a review of the symptomatology of PTSD; describes how developmental level affects the biology of the trauma response, the stress response, and the psychobiology of PTSD; and discusses the implications for psychopharmacologic treatment. PMID- 8356162 TI - Adult survivors of sexual abuse. AB - Adult survivors of child sexual abuse suffer a range of physical, psychological, and interpersonal aftereffects. These patients are increasingly evident in health care settings where they seek medical or psychological treatment for symptoms related to the abuse. The recognition of an abuse history as the traumatic antecedent is critical in differential diagnosis, treatment, and management. This paper reviews the aftereffects of child sexual abuse and provides recommendations to the primary care professional about identifying and treating adult survivors in their practices. PMID- 8356163 TI - Sadistic ritual abuse. An overview in detection and management. AB - Sadistic ritual abuse, including satanic cult abuse, is emerging as a syndrome among people with severe dissociative disorders, including multiple personality disorder. This article discusses the essential features that compose the clinical picture of sadistic ritual abuse in adults, adolescents, and children. Particular attention is paid to the differences between adolescents who may have been victimized by adults in sadistic and ritualized ways and disenfranchised "teenage dabblers" who may temporarily adopt a ritualized lifestyle as a way of expressing or acting out. The article also covers guidelines for appropriate medical, pharmacologic, and referral interventions. The controversy surrounding sadistic ritual abuse is discussed thoroughly, and primary care physicians are advised of the current status of understanding and validation in this area. PMID- 8356164 TI - The physician as perpetrator of abuse. AB - Although the exploitation and abuse of patients is forbidden by every code of medical ethics, physicians are in a power position vis-a-vis their patients, and this power may be misused. The spectrum of abusive physician behaviors includes doctors functioning as agents of control, exploiting physicianly perogatives, acting out personal problems in the medical setting, allowing subversion of their judgment, deliberately delivering suboptimal care, dehumanizing care, and sexually exploiting patients. Guidelines for the treatment of patients with such prior experiences are offered. PMID- 8356165 TI - Surviving survivors. Coping with caring for patients who have been victimized. AB - Caring for survivors of victimization is very hard work, in ways that are similar to and different from other difficult patient interactions. Careful attention to basic physiologic and psychological needs of the physicians is necessary to tolerate the stress and to prevent the burnout that can accompany this work. In addition, understanding survivors' interpersonal dynamics may help physicians provide better care. Consultation with colleagues is essential to remaining healthy and effective as givers of care. PMID- 8356166 TI - Community responses to violence. AB - Community level efforts are effective in the reduction of violence. Community level interventions have three goals: to prevent the escalation of risk for violence among the families in the community, to assist families at risk of or using violence, and to protect victims of abuse. To prevent violence or reduce its prevalence, community groups need to collaborate to reduce the community level risk factors. Assisting families and protecting victims of violence requires coordination of community services, including law enforcement, schools, therapists, courts, child care, and social services. All of these goals can best be achieved through the efforts of a community level, multidisciplinary council or board that directs the programs. A community process to establish an integrated program involves several steps. The leaders that are identified need to represent all the disciplines and the entire geographic area involved in the project. Once the leaders start meeting, the baseline information and plan can be developed. Then the project itself can be undertaken, with the support of the media and other appropriate organizations. Several examples of effective projects document this process and its success; the best efforts involve coalitions of private and governmental agencies working together. Physicians are integral to this process. The practice of medicine provides opportunities every day to prevent and intervene in potential cases of abuse and violence. Also, by participating actively in the community, physicians can be effective leaders to change attitudes and behaviors and institute programs toward reducing violence. PMID- 8356167 TI - [A case of jealous fantasy]. PMID- 8356168 TI - [A quantitative pharmaco-EEG study on psychotropic properties of cerebral metabolic enhancers: comparison between young and elderly healthy volunteers]. AB - In order to investigate psychotropic properties of cerebral metabolic enhancers (CMEs), the author carried out two identical quantitative pharmaco-EEG studies in different age groups of healthy volunteers; the young group (group-Y) consisted of six males between the ages of 21-26 years and elderly group (group-E) consisted of six males between the ages of 60-66 years. The drugs tested were five CMEs, dihydroergotoxine mesylate (DHE), propentofylline (PPF), nicergoline (NCG), lisuride maleate (LIS) and ibudilast (IDL). Each volunteer received either of the five test drugs or inert placebo in six one-day weekly sessions' according to single-blind, randomized crossover design. In each session, a single oral dose, equivalent to the clinically recommended daily dose, of either drug or placebo was administered and EEGs were recorded before and 1.3 and 6 hours after the drug administration. Firstly, the background EEGs before the drug administration were compared between the two groups. Group-E showed less slow activities and more alpha and fast activities than group -Y. This difference in background EEG profiles between two groups are considered to be due to physiological aging process. Secondly, drug effects on EEGs in two groups were compared. There were discrepancies in drug-induced EEG changes between the groups. In group-Y, any of the five tested CMEs did not induce EEG changes that were significantly different from placebo, whereas, in group-E, drug-induced EEG changes were more apparent. In group-E, DHE and PPF induced similar EEG changes, which were characterized by a decrease of alpha activity associated with marked decreases of slow and fast activities, the EEG profile similar to thymoleptics with sedative effects. LIS and IDL induced a decrease of alpha activity and an increase of fast activities, the profile close to thymoleptics with mood elevating (stimulant) effects. NCG induced an increase of slow activities, the profile close to central depressants. These results in this study coincided with the experimental and subjective classification of the clinical effects of CMEs. Further analysis of EEG profiles based on principal component analysis indicated that there were two major components in background EEGs. There were discrepancies in the response to CMEs between two groups. In group-Y, CME-induced changes were seen mainly in the second principal component, while in group-E, the changes were seen mainly in the first principal component. These results suggested CMEs provoked thymoleptic effects by affecting the essential component of the EEG basic rhythm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8356169 TI - [On compulsive hand-washing--psychopathology of "touching"]. AB - Compulsive hand-washing has been well known to the psychiatrists, since Legrand du Saulle described this disorder by the name of "delire du toucher" (1866), which refers to mysophobia or contact-phobia. But its clinical significance seems to have been not fully examined, except from the psychoanalytical point of view, that has observed the repression of sexuality in its pathology. This report presents four cases of compulsive hand-washing, and explores why they exclusively wash their hands. In order to elucidate the reason for their hand-washing and its significance, this report aims to study the relation of following three elements; "Sexuality", "hand" and "touching". As the idioms using "hand" often represent the various modes of sexual life in Japanese language as well as in English, so the "touching by hand" is reasonably considered to evoke the sexual impulsions, which the hand-washers fear and wish to avoid. On the other hand, "touching" is, necessarily in nature, to be touched by the touched object. For example, one who touches the lover's hand is inevitably to be touched by hers. That is; one is forced to be an object of one's object, which becomes to be a subject. In this sense, the act of "touching" means to lose one's "being subject" and to melt oneself into the situation where the structural distinction of subject and object can disappear. So one's act of "touching" or vivid contact with the other can cause anxiety by means of losing one's ego, which may be also a critical point to introduce to create something new. A compulsive hand-washer fears and avoids this critical moment that can make him lose his "being subject", so he "washes his hands of (cuts off relation with)" the situation that can undermine his ego. This avoidance of having contact can be compared to "the lose of vivid contact with the reality (la perte du contact avec la realite (Minkowski)" observed in schizophrenia. In their ways of life, many hand-washers are not less autistic than the schizophrenics.om PMID- 8356170 TI - [Human values and respect of human rights in oppressive conditions]. AB - Human rights, an issue of political debates in the last decades, listed in the United Nations Declaration of 1946 are rooted in the humanistic tradition of philosophy and religion. The UN declared their universal character and made state organizations responsible for their observation. Among all human rights that for freedom is usually perceived as crucial. Psychiatry developed in Europe primarily a caring function. The medical model developed in psychiatry through the 19th c. supplied the criteria for medical diagnosis of mental disturbance, and elaborated a system of treatment which included long term hospitalization. Medicalization of psychiatry (recently coming back) is a force which gives courage to those who suffer, to their families, and to professionals as well. This power however, can be easily abused, when a psychiatrist adopts a position of someone who knows better that which is good for his/her patient. Legal regulations of the circumstances of psychiatric treatment, especially treatment against the patient's will should prevent the abuse of the mentally disturbed person's right for freedom. The goal is usually achieved by clear description of clinical and other conditions under which a person can be committed, and by establishing the committed person's right to claim the decision to be unjust. Poland is a country without legal regulation in the area of mental health (there are only administrative acts). For more than sixty years several projects on mental health law have been worked on. The last one which came to the Sejm (parliament) in 1980 was withdrawn by the "Solidarity" Trade Union. At present, the membership of Poland in international organizations makes an introduction of mental health law an obligation. Having no legal regulation, Polish psychiatry has been a self regulating system. It is worth to note that even in the hard Stalinist period (1947-1956) there was no abuse of psychiatry for political reasons. The main reason for Polish psychiatry staying free from political abuse is seen in the role of internalized norm of human dignity. But others should also be taken into account. It was a specificity of the political situation that the ruling powers did not insist that psychiatrists cooperate. On the other hand the integration of the Polish psychiatric community was helpful in observing the rule of non collaboration. One of the most important factors is seen as the experience and memory of NAZI crimes in the field of psychiatry in Poland. Extermination of psychiatric patients had to leave the feeling of the importance of psychiatrist's own responsibility.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8356171 TI - [Panel discussion at the 37th Congress of Polish psychiatrists in Poznan in May, 1992]. PMID- 8356172 TI - [Confrontation with frustration in psychiatric practice]. AB - In the educational programs for psychiatrists one often meets emissions in the confrontation with difficult situations during the first steps in that specialty. In the background of frustrogenic cases, which trainees have in their first years of their practice, the author outlines an adequate program, which could improve this situation. A discussion about these themes would also be useful in postgraduate training. PMID- 8356173 TI - [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. PMID- 8356175 TI - [Further research into the formation of the syntonic-autistic relationship in paranoid schizophrenia]. AB - Research was conducted on a sample of 100 patients. The diagnosis was carefully verified according to the DSM-III. The "Syntonic" Scale and the "Autism" Scale, described in a separate paper were used. A literature review was performed with special attention to the fact that surprisingly rarely are references made to syntonia in research upon schizophrenic patients. The results are presented in table 1 and Figures 1 and 2. In all of the 100 subjects both factors studied were present though to varying degrees of severity. Both factors showed evident characteristics of selectivity. The numerical data revealed a definite predominance of autism over syntony, which is a well known fact in schizophrenia, however, of significant importance is the presence of syntony as an additional factor. The correlation variable of both scales is expressed by r = -0.79, which indicates that there is a strong negative relationship. For the needs of further analysis the groups were split into smaller subgroups. Subgroup I was characterized by the predominance of autism over syntony (47 cases). In subgroup II a predominance of syntony over autism was found (33 cases). On the basis of greater confidence the subgroup III was described, which contained the cases in which neither factor was predominant (20 cases). The majority of the sample of patients ill with schizophrenia showed the ability to react syntonically. The obtained results support the view that autism and syntony are two poles of the same dimension, they also support the hypothesis which states that there is evidence to suggest that the are two basic subgroups of paranoidal schizophrenia. PMID- 8356174 TI - [Computer tomography in diagnosis of mental disorders]. AB - The article includes a review of literature discussing the results of CT (computed tomography) usage with psychiatric patients and a range of recommendations for using this diagnostic method in psychiatry. Recommended indications for ordering a CT scan for psychiatric patients have ranged from narrow guidelines (only patients with focal neurological findings) to a broad spectrum, including any of the following: confusion and/or dementia of unknown cause, a first episode of a psychosis of unknown etiology, a movement disorder of unknown etiology, a diagnosis of anorexia nervosa, prolonged catatonia, and a first episode of major affective disorder or personality change after 50. PMID- 8356176 TI - [Further research into the formation of the "vitality and adequacy of emotion emotional blunting" relationship in paranoid schizophrenia]. AB - A sample of 100 paranoidal schizophrenic patients were assessed. Scales of "vitality and the adequacy of emotion" and "emotional blunting" which are described in a separate paper were used. At the beginning attention was focused on the fact that several synonimous terms are used to describe the blunting of emotion (flatness of affect, blunted or inappropriate affect, presence of affect as opposed to flatness). The results indicate that in only a very few cases the intensity of both studied qualities was negligible, however in the majority of the cases it appeared that the quality of "vitality" and its opposite is present. In 62 patients the emotional blunting was moderate. Emotional vitality in these cases remained in the wide range from moderate to significant. Both factors may be considered to be additional factors on the basis of the size and type of correlation. The coefficient of both Scales is expressed by r = -0.77. The correlation between the studied proportion and the syntonic-autistic proportion is expressed by r = 0.69. The cases of emotional blunting which occurred at different levels of intensity were generally accompanied by relative vitality and adequate emotional reaction. The formation of the studied proportion and in particular the high correlation coefficient between this proportion and the syntonic-autistic proportion suggests that autistic schizophrenia and syntonic schizophrenia form two basic subgroups of paranoidal schizophrenia. PMID- 8356177 TI - [The disturbance of the sense of time in schizophrenia]. PMID- 8356178 TI - [Current views of the mechanism of action of antidepressants]. AB - Considering the ever growing number of new discoveries and changes in ideas in the field of psychopharmacology, the authors present the actual state of knowledge about the mechanism of action of antidepressant drugs. Three periods characterize the research and the development of antidepressants. In the first period the presynaptic monoamine neuron was considered as the target structure both with respect to the search for the origin of depression and the mechanism of action of antidepressants. Two types of antidepressants, monoamine uptake inhibitors and monoamine oxidase inhibitors (IMAO) are representative of this period. In the second period, the research focused its interest primarily on monoaminergic receptors, anticipating that they were critically involved in the pathophysiology of depression. Such research sought to explain the antidepressant properties of iprindole and mianserine which are neither monoamine uptake inhibitors nor inhibitors of MAO. The onset of the third period is recent and it is characterized by the shift in research emphasis to intracellular transmission events. This period started with the discovery of the antidepressant properties of the phosphodiesterase inhibitor rolipram. PMID- 8356179 TI - [Rat's nigrostriatal dopamine system under the influence of insulin in alloxan diabetes]. PMID- 8356180 TI - A description of the forensic outpatient and the opinions of mental health professionals who work with these clients. AB - This paper presents a descriptive profile of clients placed on Conditional Release in New York State between September 1980 and September 1987 (N = 331). Data on the client's sociodemographic characteristics, prior mental health history, prior criminal justice history, and target offense are presented, as well as information on the conflicts faced by the primary therapists working with this population. PMID- 8356181 TI - The assessment of dangerousness and predictions of violence: recent research and future prospects. AB - Recent research on clinical and actuarial assessments of dangerousness leaves many important questions unanswered regarding the relative validity and utility of such assessments. Moreover, the focus that has existed on determining the false-positive and false-negative rates of predictions of violence may be fundamentally misplaced. Clinical evaluations of dangerousness should be viewed as assessments of risk rather than as predictions of violence; and future research should focus on understanding and evaluating how clinical assessments of dangerousness-regarding truly representative types of possibly dangerous patients -are (or should be) made. In the meantime, the research to date on clinical assessments of dangerousness cannot properly be taken to conflict with the Supreme Court's recent affirmations of the admissibility of such assessments in courtroom proceedings. PMID- 8356182 TI - The ongoing risk assessment in the treatment of forensic patients on conditional release status. AB - In New York State, patients who have been found not criminally responsible by reason of mental disease or defect, eventually become outpatients while still under the supervision of the courts. The treatment of these patients on outpatient orders of condition poses special problems. Treatment needs to center on the issues related to patient's potential for harmful/violent behavior. Therefore, outpatient clinicians need to conduct periodic risk assessments and must continuously monitor identified risk indicators. The author outlines steps for information gathering and evaluation necessary for risk assessment. Treatment of these patients is conceptualized as ongoing clinical risk identification and management. It is framed by a treatment contract that integrates mandates of the Orders of Conditions with information gathered through ongoing risk assessments and spells out legal and other consequences that may arise from non-compliance. PMID- 8356183 TI - Providing outpatient services to criminal procedure law patients: the clinician's perspective. AB - This presentation identifies a number of the elements involved in implementing an effective program for the care and treatment of the Conditionally Released CPL Patient. The component parts to be explored include: societal and agency issues, the identified patient and, issues relating to the clinician and the clinical treatment team. The outpatient clinician fulfills numerous role/task functions. The roles of therapist, educator, teacher, advocate, casemanager, and "parole officer" will be discussed. Techniques for identifying and working through the worker's own "blocks" will be discussed as a prelude to establishing a therapeutic alliance. Principles of utilizing authority and contracts as basic therapeutic techniques will also be noted. Recognizing that the patients who comprise the conditionally released CPL 330 category are heterogeneous and multiply disabled, techniques for active focused rehabilitation treatment will be explored. PMID- 8356184 TI - Semiotic aspects of cognitive development: illustrations from early mathematical cognition. AB - The premise of this article is that cognitive development involves both conceptual and semiotic achievements. From this perspective, the authors emphasize the distinctness of the semiotic issues and develop a differentiated appreciation of semiotic aspects of cognition, particularly in the field of elementary mathematical cognition. The authors provide semiotic analyses of the differences between counting, adding, and multiplying and of the conventional place-value sign system. The authors introduce the concept of the field of reference of a sign, the differentiation of the field into foreground and background, and the dynamics within the field of reference. Finally, the authors relate these ideas to the dynamics between two dimensions of semiotic relations: the sign-referent dimension and the sign-sign dimension. PMID- 8356185 TI - Decision field theory: a dynamic-cognitive approach to decision making in an uncertain environment. AB - Decision field theory provides for a mathematical foundation leading to a dynamic, stochastic theory of decision behavior in an uncertain environment. This theory is used to explain (a) violations of stochastic dominance, (b) violations of strong stochastic transitivity, (c) violations of independence between alternatives, (d) serial position effects on preference, (e) speed-accuracy trade off effects in decision making, (f) the inverse relation between choice probability and decision time, (g) changes in the direction of preference under time pressure, (h) slower decision times for avoidance as compared with approach conflicts, and (i) preference reversals between choice and selling price measures of preference. The proposed theory is compared with 4 other theories of decision making under uncertainty. PMID- 8356186 TI - The perception of natural contour. AB - The observation that natural curves and surfaces are often fractal suggests that people may be sensitive to their statistical properties. The perceptual protocols that underlie discrimination between fractals and between other types of random contour and fractals are examined. Discrimination algorithms that have precisely the same sensitivities as human observers are constructed. These algorithms do not recognize the integrated scale hierarchy intrinsic to fractal form and operate by imposing a metatheory of structure that is based on a signal-noise distinction. The success of the algorithms implies that (a) self-affinity in random fractals is not perceptually recovered and (b) people have a natural disposition to view contour in terms of signal and noise. The authors propose that this disposition be understood as a principle of perceptual organization. PMID- 8356187 TI - Social contagion and adolescent sexual behavior: a developmental EMOSA model. AB - Epidemic Models of the Onset of Social Activities (EMOSA models) describe the spread of adolescent transition behaviors (e.g., sexuality, smoking, and drinking) through an interacting adolescent network. A theory of social contagion is defined to explain how social influence affects sexual development. Contacts within a network can, with some transition rate or probability, result in an increase in level of sexual experience. Five stages of sexual development are posited. One submodel proposes a systematic progression through these stages; a competing submodel treats each as an independent process. These models are represented in sets of dynamically interacting recursive equations, which are fit to empirical prevalence data to estimate parameters. Model adjustments are substantively interpretable and can be used to test for and better understand social interaction processes that affect adolescent sexual behavior. PMID- 8356188 TI - Metrics and mappings: a framework for understanding real-world quantitative estimation. AB - Estimation is influenced by a variety of processes: application of heuristics, domain-specific reasoning, and intuitive statistical induction, among them. In this article, we propose the metrics and mapping framework to account for how these processes are integrated to generate estimates. This framework identifies 2 types of information as critical: knowledge of distributional properties (metric knowledge) and knowledge of relative status of individual entities within the distribution (mapping knowledge). Heuristics and domain-specific knowledge are both viewed as cues that contribute to mapping knowledge; intuitive statistical induction is viewed as providing cues to metric properties. Results of 4 experiments illustrate the framework's usefulness for integrating these types of information and for predicting when people emphasize heuristics and when they emphasize domain-specific knowledge. PMID- 8356189 TI - The regularities of recognition memory. AB - Three regularities in recognition memory are described with supporting data: the mirror effect, the order of receiver operating characteristic slopes, and the symmetry of movement of underlying distributions. The derivation of these regularities from attention/likelihood theory is demonstrated. The theory's central concept, which distinguishes it from other theories, is the following: Ss make recognition decisions by combining information about new and old items, the combination made in the form of likelihood ratios. The central role of the likelihood ratios extends the implications of signal detection theory for recognition memory. Attention/likelihood theory is fitted to data of 2 series of experiments. One series involves yes-no tests and confidence ratings, the other forced-choice experiments. It is argued that the regularities require a revision of most current theories of recognition memory. PMID- 8356190 TI - The influence of perceptual and motor factors on bimanual coordination in a polyrhythmic tapping task. AB - In this study the role of perceptual and motor factors on the motor organization (integrated versus parallel) adopted by musically skilled and unskilled subjects in a polyrhythmic tapping task was investigated. Subjects tapped a 3:2 polyrhythm to match the timing of two isochronous tone trains, one tone train for each hand. Perceptual factors were examined by the manipulation of the frequency difference between the tone trains to produce either an integrated or a streamed percept. Motor factors were examined by comparison of performance on two versions of the 3:2 polyrhythm. In one (simultaneous) version, each cycle of the polyrhythm began with a simultaneous left- and right-hand tap. In the other (shifted) version a 100-ms interval was introduced between the initial left and right taps in each cycle. Examination of the pattern of variances and covariances among intertap intervals suggested that most of the subjects in this study adopted an integrated motor organization that involved interleaving the timing of the two hands. Further analysis revealed that a serial chained model described the pattern of covariances best for the simultaneous pattern, whereas a hierarchical organization described the pattern of covariances for the shifted pattern best. The finding that performance was more accurate with integrated tones than with streamed tones provides some support for a perceptual-motor facilitation hypothesis. PMID- 8356191 TI - The effect of temporal and force changes on the patterning of sequential movements. AB - This article examines the programming of relatively long sequences of action with the control of sequential movements being effected through the use of a tapping task involving a sequence of five taps. Subjects were required to tap with their right hand at rates of 150, 200, and 250 ms. There were two conditions, with subjects being required either to increase, in condition 1, or to decrease, in condition 2, the force at one of the five tap positions (all five tap positions were examined), then return to the previous force level. Changes in timing resulting from variations in the force characteristics have previously been discussed in terms of changes in the organizational time required (Semjen, Garcia Colera, & Requin, 1984). The current study breaks the intertap interval down into two separate components: the contact interval (finger in contact with the key) and the non-contact interval (interval preceding the tap). Although changes in the non-contact interval could be explained in terms of changes in the organizational time required, changes in the contact interval appeared to be a result of the mechanical changes in force. PMID- 8356192 TI - Central and peripheral coordination in movement sequences. AB - Motor coordination has been too poorly defined to be a useful construct in studying the control of movement. In general, motor coordination involves controlling both the timing and the kinematics of movement. Yet the motor behaviors typically used for the study of coordination have required controlling only the timing or the spatial aspects of a movement. To understand better the basis of motor behavior, this study examined movement sequences, a class of movement in which both the timing and the kinematics must be controlled. In one experiment we studied a reaching and grasping movement sequence to characterize the central coordination of movement sequences. In another experiment we studied a throwing movement sequence to characterize the peripheral (kinesthetic) coordination of movement sequences. An heuristic model is presented to explain how central and peripheral mechanisms of coordination might interact to produce accurate movement. PMID- 8356193 TI - Searching for the minimal essential information for skilled perception and action. AB - A common concern for both cognitive/computational and ecological/dynamical models of human motor control is the isolation of the minimal essential information needed to support skilled perception and action. In perception isolating essential features of the optic flow field, which are reliably informative regarding the nature of current events, from nonessential features provides a valuable step towards understanding how the computational complexity of perceptual information processing may be reduced to manageable levels and how relatively direct linkages of low dimensionality may be established between information and control variables. Likewise, in the study of action, discrimination of the movement features that remain immutable (invariant?) across changes in task conditions from the variables that are situationally determined provides a principle insight into the structural framework upon which skilled movement is built. Controversy abounds, however, in the study of perception and action as to whether features isolated as informative and immutable are centrally represented (in the form of a template or program) or are rather directly picked up (in the case of perceptual variables) or are simply an emergent consequence of the underlying dynamics (in the case of action variables). In this paper some examples of putative minimal essential information sources in perception and action are provided, strategies for uncovering such sources are discussed, and attention is directed, with the use of some recent data collected on natural skills, to some systematic expert-novice differences in the utilization of essential information and control variables. Expert-novice differences are highlighted because of the insight they may provide regarding the nature of perceptual-motor skill acquisition. PMID- 8356194 TI - Detection and execution of movements. AB - Detection thresholds for movements imposed on the relaxed joints in upper limbs, when expressed in terms of angular or linear displacement, differ from joint to joint. However, when they are expressed in terms of proportional changes in the lengths of fascicles of the muscles serving the joints, they are found to be similar. When the execution of finely graded voluntary movements is analysed, performances of similar accuracy occur when the movements at different joints require alterations of the lengths of active muscle fascicles by similar proportions. These findings suggest that muscle length is a variable of importance to the CNS in both the detection and execution of movements. For faster contractions, another category of movement must be considered. This is the triggered response, which can be voluntarily pre-formulated and stored in the brain, to be released subsequently by some sensory input. Such triggered responses can be demonstrated in experiments in which subjects respond to masked stimuli--low-intensity sensory stimuli which, while readily detected when presented alone, are not detected when followed very soon afterwards by a high intensity stimulus. Subjects are able to react with simple and more complex movements to low-intensity stimuli whether these are detected (delivered alone) or undetected. PMID- 8356195 TI - Judgments of moving and intending to move in a timed-response task. AB - Subjects performed a timed-response task in which they attempted to synchronize a rapid flexion of the index finger of their preferred hand with the last of a train of four regularly spaced acoustic clicks. The task was used to stabilize the execution time of a simple voluntary response in order to facilitate psychophysical judgments about the subjects' perception of having responded and of having intended to respond. In the first experiment, male subjects (N = 6) adjusted the appearance time of a reference stimulus (a brief percutaneous pulse to the responding finger) until it appeared to be simultaneous with their perception of having made the response. All subjects adjusted the reference stimulus to appear after response onset during the latter half of the force impulse. This finding suggests that the perception of having responded is based on peripheral feedback from the response. In the second experiment, male subjects (N = 6) performed the same motor task, but adjusted the time of the reference stimulus so that it appeared to be simultaneous with their intention to respond. Two subjects were not able to do the task successfully; the remaining four subjects adjusted the reference stimulus to appear from 101 to 145 ms before response onset. This finding suggests that the intention to respond is perceptually separable from the response itself and occurs at a measurable time before response onset. PMID- 8356197 TI - Correction processes in early reaching: reaches by infants to prismatically displaced targets. AB - A comparison was made between trajectories of reaches to visual targets by 6 months-old infants, with and without lateral prismatic displacement. In the No Prism condition, the major element of the movement veered towards the target, confirming the results of Mathew and Cook (1990). In the Prism condition, the prism did not affect hand position or movement direction at the beginning of the major element, but a lateral displacement was evident by the end of the element. This is taken as evidence that shifts in trajectory during the element were not due to visual guidance. It is suggested instead that these shifts may reflect correction based upon somatic feedback about position in relation to the visually specified goal of the movement. Evidence that the hand approached the virtual target supports the suggestion that any visual guidance was confined to the approach phase of the reach. Nevertheless, it appears that visual guidance was operating at this stage, since movement direction was displaced away from the virtual target and towards the real target. PMID- 8356196 TI - The amendment of large-magnitude aiming-movement errors. PMID- 8356198 TI - Perceptual-motor development and prevention of clumsiness. AB - This longitudinal study, following children's development over three years, examines the developmental trends in the processes underlying perceptual-motor behaviour. Entry into the study was at first year of primary school, at age 6. The study has three aims: (1) to obtain developmental trends in kinaesthesis and motor-programming processes; (2) to examine the relationship between slow kinaesthetic and motor development; (3) to establish the effect of accelerated kinaesthetic development and prevention of perceptual-motor dysfunction (clumsiness). The results to date show that over 60% of children entering primary school have not developed the kinaesthetic ability necessary for the acquisition and learning of educationally demanded motor skills. Kinaesthetic development is accelerated spontaneously in some children as a response to educational demands; in others a single exposure to kinaesthetic input triggers significant improvement. In the remaining 17% kinaesthetic training can alleviate the kinaesthetic dysfunction. At age 5-6 years only 25 children (8.1%) performed the Perceptual-Motor Abilities Test at levels indicative of perceptual-motor dysfunction. Of these, 13 children (4.2%) were identified as having motor difficulties. These low incidence rates indicate that a low level of kinaesthetic ability has no effect on general motor function at the beginning of schooling, and that only when competence in complex motor skills is expected, from the third year of schooling, does perceptual-motor dysfunction (PMD) become manifest. PMID- 8356199 TI - Motor functions of the basal ganglia. AB - A study of movement disorders such as Parkinson's disease and Huntington's disease can provide an indication of the motor functions of the basal ganglia. Basal-ganglia diseases affect voluntary movement and can cause involuntary movement. Deficits are often manifested during the coordination of fine multi joint movements (e.g., handwriting). The disturbances of motor control (e.g. akinesia, bradykinesia) caused by basal-ganglia disorders are illustrated. Data suggest that the basal ganglia play an important role in the automatic execution of serially ordered complex movements. PMID- 8356200 TI - Stability and change in children's skill. AB - This paper explores age-related performance variability, both within trials and between sessions, in repetitive hopping. The mean, the standard deviation (SD), and the coefficient of variation (CV) of several timing and ground-reaction-force variables of hopping were analysed by repeated-measures ANOVA for age-related effects across test sessions and foot used. Forty-five subjects in five age groups (3-4 years, 4-5 years, 6-7 years, 8-9 years, or Adult) performed self paced, one-footed hopping on three occasions within one week. As was expected, the results showed main effects for Age in all force and time variables, with the exception of CV of medio-lateral force. No significant main effects for Feet were revealed. However, significant Feet x Session interactions were found in flight time measures, with higher flight-time SD and lower CV for the non-preferred foot in Session 1, a reversal in Session 2, and a negligible difference in Session 3. Across sessions, decreased SD and CV for both vertical and medio-lateral force and shorter flight time indicated more efficient hopping. Overall, it was concluded that SD and CV measures were more sensitive measures of children's performance across repeated sessions than were mean scores and that the order of testing the limbs is an important consideration in experimental protocols when lateralized tasks are measured. PMID- 8356201 TI - Motor control and sensory-motor integration. PMID- 8356203 TI - Public health research. PMID- 8356202 TI - Structural constraints on bimanual movements. AB - A theoretical framework is outlined, according to which structural constraints on bimanual movements can at least in part be understood as coupling between parameters of generalized motor programs. This framework provides a conceptual link between reaction-time data from experiments with bimanual responses, successive unimanual responses, and choice between left-hand and right-hand responses on the one hand and performance data obtained with concurrently performed continuous movements or sequences of discrete responses on the other. On the basis of data obtained with different methods for the study of intermanual interactions, a distinction is drawn between steady-state and transient constraints, and the hypothesis that the tendency to coactivate homologous muscles originates from a transient coupling of program parameters is applied to a variety of observations on performance in different tasks. Finally, the notion of transient constraints is applied to other types of intermanual interdependencies, and to interpersonal coordination; the possible emergence of transient constraints from steady-state constraints through progressive development of inhibitory pathways in childhood is discussed, as is the potential biological significance of transient constraints. PMID- 8356204 TI - 9th Duncan Memorial Lecture, University of Liverpool, November 1991. Gaia and health. PMID- 8356205 TI - How do we measure consumer opinions of outpatient clinics? AB - Consumer opinion of care in outpatient departments is increasingly seen as an important measure in the process of quality assurance. However, there are many ways of measuring consumer opinion. The aim of this series of studies was to compare different methods so as to throw light on when and where to use them. What is revealed is that there is no one right answer; instead, a combination of methods will allow the development of a balanced view of consumer opinion and an agenda for action. PMID- 8356206 TI - Maternal and child health services: evaluating mothers' perceptions and participation. AB - Urban mothers' perceptions and their actual practices in respect of antenatal care, postnatal care, childbirth and breast-feeding were reviewed through a predesigned questionnaire provided to all mothers (n = 114) staying for a day in the Clinical Research Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh. Only 8% of mothers surveyed were pregnant and 71% had access to a maternal and child health clinic near their homes. Although 61% of the mothers replied that antenatal care is needed, 45% of all mothers actually used the service. Similarly, 79% of them felt that postnatal care is needed, yet only 26% attended the clinics. Only 6% of all mothers had their previous children delivered at a hospital or clinic. The majority (91%) were delivered at home, traditional birth attendants assisting in childbirth in most cases (74%). In spite of mass campaigning against the use of pre-lacteal foods (like honey and sugar water), these were given to 90% of the newborns. Underutilization of maternal and child health clinics was mostly due to the clinics only being open during the busy hours of family work and because of the misbehaviour of the staff. Changing clinic opening times, supervising staff properly and educating mothers will help to overcome their taboos and to motivate them to use 'institutional services'. PMID- 8356207 TI - Social class and health behaviour in Danish adults: a longitudinal study. AB - Health behaviours were examined in a random sample of 3,608 men and women aged 30, 40, 50 and 60 years, living in the western part of Copenhagen, Denmark. Data were collected by standardized questionnaires completed by each individual in 1982 and by 2,987 subjects who attended for follow up five years later. Smoking, leisure time inactivity and infrequent intake of vegetables were interrelated and highly influenced by social class. Between 1982 and 1987 the proportion of smokers decreased in both sexes. However, an inverse association with social status persisted in the men and increased by 8% in the women. The proportion of physically inactive subjects remained nearly constant. Infrequent intake of vegetables decreased in both sexes, but an inverse association with social status persisted in men and increased by 10% in women from 1982 to 1987. In the multivariate analysis high social status predicted quitting smoking in both sexes and increased intake of vegetables in women. It is suggested that the inequalities in health behaviours between social status groups may to some extent be attributed to the way health promotion has been carried out in Denmark. This observation provides a challenge for the future design of effective public health strategies. PMID- 8356208 TI - A study of some psycho-social characteristics of blind and deaf male students in Abha City, Asir region, Saudi Arabia. AB - Psychosocial characteristics including depression, attitude towards their handicap, hobbies and problems of living situations have been studied among 152 male students in the Institute for the Blind (n = 44) and in the Institute for the Deaf (n = 108) in Abha City. All students were subjected to a constructed Arabic version of the rating scale 'Children Depression Inventory (CDI)'. They were categorised according to their scores on this CDI, into depressed and non depressed. Also, an interview questionnaire was administered to collect data related to the handicap, such as age of onset, and its cause and family history of the same handicap. The effect of the handicap upon the attitudes of students in relation to their social tendencies, hobbies and problems in living situations was studied. The mean ages for blind and deaf students were 15.70 and 13.04 years respectively. About 91.% and 75.% of blind and deaf students respectively were born with their handicap. Depression was more prevalent among the blind (14%) than among the deaf (6.5%) students. Difficulty in mobility was the main problem among blind students (44%) while difficulty in communication with people was the main problem among the deaf (52%). Reading was the commonest hobby for the blind (51%), while playing football was the commonest among the deaf (62%). This information should be considered when planning for rehabilitative services for these groups. PMID- 8356209 TI - Trends in nutrition in Greece: use of international data to monitor national developments. AB - With the purpose of studying trends in nutrition in Greece, data from the Food Balance Sheets about the calorie and nutrient intakes were analysed. During the period 1961-86, the average per capita consumption of calories increased by 26.6%, while the calories obtained exclusively from animal sources increased by 106%. The average protein intake rose by 29.9%. Animal proteins increased by 90.6% and their proportion reached 51.5%. Lipid intake increased by 62.2%; in particular animal fats went up by 114.3%. It is concluded that the most important changes in nutrition in Greece during the study period were (a) the increase in total calorie intake, and (b) the rise in total fat consumption and especially the vertical increase in consumption of animal fats. These developments show a change to the traditional pattern of the Greek diet. PMID- 8356210 TI - Chemical disasters, real and suspected. PMID- 8356211 TI - Control of falciparum malaria. PMID- 8356212 TI - Design and discovery of new drugs by stepping-up and stepping-down approaches. PMID- 8356213 TI - Present status of luteolytic agents in fertility regulation. PMID- 8356214 TI - Aldose reductase inhibitors: recent developments. PMID- 8356215 TI - [Structure of 3-isopropylmalate dehydrogenase from an extreme thermophile--a new model enzyme molecule for the study of structure-function and structure-stability relationships]. PMID- 8356216 TI - [Recent progress of mitochondrial fatty acid oxidation system]. PMID- 8356217 TI - [The contractile proteins and the contractile apparatus of platelets]. PMID- 8356218 TI - [What brings certain molecular species of membrane phospholipids?]. PMID- 8356219 TI - Management of Hodgkin's disease patients with mediastinal adenopathy and pulmonary involvement (stage IIE). AB - Two hundred and fifty-five patients with Hodgkin's disease and with localized pulmonary involvement (Stage IIE) were retrospectively assessed for their response to different treatment programmes while considering the size of mediastinal lymph nodes and the extent of pulmonary disease (involvement of lung subsegment, segment or lobe). Five-year overall and disease-free survival rates in 255 patients were 89.6% and 72.3%, respectively. In patients with mediastinal index < 1/3 and lung segment and/or subsegment involvement, 5-year overall and disease-free survival rates were 96.6%. For patients with mediastinal index > 1/3 and similar lung involvement the corresponding values were, respectively, 88.6% and 73.5%; and for those with a lung lobe involvement the values were 76.4% and 56.7%, respectively. Patients were treated according to the following programmes: 1 combination chemotherapy cycle + radiotherapy (RT) + 4-5 combination chemotherapy cycles; 3 combination chemotherapy cycles + RT; 6 combination chemotherapy cycles + RT. The best results were obtained with the programme consisting of 1 combination chemotherapy cycle + lymphoid irradiation above the diaphragm and irradiation of the spleen to a total tumour dose of 40 Gy and irradiation of involved lung sites to a total tumour dose of 20 Gy + 4-5 combination chemotherapy cycles. PMID- 8356220 TI - Radiotherapy for supratentorial low-grade gliomas: results and prognostic factors with special focus on tumour volume parameters. AB - From 1973 to 1990, 67 patients with a diagnosis of low-grade glioma were treated in our hospital. Overall survival was analysed as well as the influence of patient, tumour- and treatment-related factors with special focus on tumour volume parameters. Our study group included 49 patients treated by surgery and post-operative radiotherapy (RT) (40 patients) or post-biopsy irradiation alone (9 patients). Total or almost total resection was performed in 16 patients; partial excision was done in 24. With the available pre-surgery and pre-RT CT scan and/or MRI images we were able to calculate tumour volumes by measuring the largest tumour dimensions in the three axes D1, D2, D3 and by assuming an ellipsoidal growth (i.e., tumour volume = D1D2D3 pi/6). RT was delivered to involved regions: either the residual tumour volume or the tumour bed. The median RT dose was 56 Gy (45-60, range). The 60- and 90-month overall survival (Kaplan Meier) was 79% and 67%, respectively. Female sex, > 70% Karnofsky (Kf) score, oligodendroglioma and < 71 cm3 (approximately 5 cm diameter sphere) tumour residuals before RT were associated with better overall survival rates (p < 0.05, log-rank). However, a Cox proportional hazards model showed that only the histological subtype and Kf significantly determined the patients' outcome: 60 month overall survival of 100%, 62%, 83% and 64% for oligodendrogliomas, mixed oligo-astrocytomas and grade-I and grade-II astrocytomas, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356221 TI - Blood tests and prognosis in bladder carcinomas treated with definitive radiotherapy. AB - The value of some commonly recorded blood tests as prognostic factors in patients with bladder carcinomas treated with definitive radiotherapy has been assessed. This study included 202 consecutive patients (T2, n = 46; T3, n = 82 and T4, n = 74) treated during the period 1980-1987. The median total dose received was 56 Gy [50-67] and the median cumulative radiation effect was 1750 reu (radiation effect unit) (1515-1823). The blood tests examined in survival analyses were erythrocyte sedimentation rate (ESR), hemoglobin (Hb), leucocyte and thrombocyte count, alkaline phosphatase (ALP), gamma-glutamyltransferase (GT), lactate dehydrogenase (LD), creatinine and albumin. In the univariate survival analyses six blood tests were significant prognostic factors (ESR, albumin, creatinine, Hb, ALP and GT). In the multivariate analysis of all 202 patients, the following five variables were significantly associated with shorter survival: T4 tumors, ESR > 30 mm/h, albumin < 35 g/l, LD > 400 U/I and age > 75 years. Our conclusion is that several commonly recorded blood tests are powerful prognostic factors in bladder cancer treated with definitive radiotherapy. These tests can replace other more expensive laboratory investigations used for prognostication. PMID- 8356222 TI - Changes in the oxygenation of head and neck tumors during carbogen breathing. AB - The oxygenation of head and neck tumors and changes during carbogen breathing were assessed in 20 patients. The median oxygen tension (pO2) for each patient was lower in tumors before breathing carbogen than in normal tissues. The median pooled pO2 of all the tumors was 20 mmHg; for normal tissue it was 60 mmHg. Low values (below 10 mmHg) were found in 4 patients for the normal tissue and in 18 patients for tumors. During carbogen breathing, the median (61 mmHg) pO2 readings for all tumors was higher than that recorded before carbogen breathing. The frequency of low (< 10 mmHg) pO2 values decreased with carbogen breathing in 11 patients; only 4 patients still exhibited very low values (< 2 mmHg). Maximal effect was obtained within 1-6 min of gas exposure. The pO2 stayed high under carbogen breathing in 15 out of 16 patients. Return to pre-carbogen levels of oxygenation occurred in 1 min after the end of gas exposure. These data suggest that carbogen breathing increases tumor oxygenation as assessed by polarography. The breathing time appears to be important for therapeutical use and should to be taken into consideration. PMID- 8356223 TI - Nicotinamide pharmacokinetics in humans and mice: a comparative assessment and the implications for radiotherapy. AB - Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested. The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed in female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed similar characteristics as the human data, although the elimination half lives were not dose-dependent. The average peak plasma concentration of 160 micrograms/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a regrowth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 100-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation response. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours. PMID- 8356224 TI - Effects of the radiosensitising agent nicotinamide on relative tissue perfusion and kidney function in C3H mice. AB - Nicotinamide is an effective radiosensitiser of murine tumours, functioning by improving tumour perfusion by decreasing the proportion of intermittently closed capillaries. The effect of nicotinamide on relative tissue perfusion of RIF-1 tumour and normal skin, muscle, lung, liver, kidney and spleen were investigated using the 86Rb extraction technique. A dose of 1000 mg/kg was shown to have transient effects on tumour, skin and lung perfusion but to have sustained effects on muscle (a drop to 80% of control), liver, kidney and spleen (with increases ranging from 165% to 280% of control) from 0.5 to 4 h after treatment i.e. during the period of maximum radiosensitisation. These increases were evident at doses as low as 100 mg/kg. The data suggest that the radiosensitisation induced by nicotinamide in the mouse may be associated with these perfusion changes. Nicotinamide was also shown to have a substantial inhibitory effect on renal function, inhibiting 51CrEDTA clearance by a factor (+/- 2 SE) of 2.56 +/- 0.19 and 125I-iodohippurate clearance by a factor of 2.07 +/- 0.45 at 1000 mg/kg. These effects were shown to be dose-related, and to be evident at doses from 400 mg/kg upwards. This suggests that nicotinamide potentiation of co-administered cytotoxic agents may be mediated by reduced renal clearance of the cytotoxic drug, thus increasing the plasma half-life. PMID- 8356226 TI - Dose intercomparison at the radiotherapy centers in The Netherlands. 3. Characteristics of electron beams. AB - Dosimetric characteristics of a number of clinically applied electron beams were analyzed as part of a dosimetry intercomparison program performed at the radiotherapy centers in The Netherlands. Absorbed dose values, determined under reference conditions, were compared during site visits with stated dose values. The mean deviation was 0.2% with a standard deviation (SD) of 2.5%. The maximum deviation was 5.7%. The largest differences were due to differences in the calibration procedures and differences in the numerical values of conversion factors adopted from different dosimetry protocols. In addition, a number of clinically relevant parameters of the dose distribution on the central beam axis were analyzed including the depth of the 85% and 50% relative dose, the dose reduction at the depth of the 50% relative dose and the surface dose. The average difference between the stated and measured therapeutic depth (85% dose level) was -0.4 mm with an SD = 1.2 mm. Due to this dosimetric uncertainty observed a safety margin of about 3 mm at the therapeutic depth is recommended. The maximum difference between stated and observed mean energy of the electron beams had only a small influence, < 1%, on the absorbed dose determination. The normalized dose gradient is not an adequate parameter to describe the dose reduction beyond the therapeutic depth. The depth of a low dose level is a better parameter. The relative dose at the surface showed differences up to 10% between scanning electron beams and beams from accelerators with a single scattering foil and closed wall collimating system. PMID- 8356225 TI - Radiosensitivity, blood perfusion and tumour oxygenation after perflubron emulsion injection. AB - The effect of 90% and/or 100% w/v perflubron (perfluorooctyl bromide (PFOB); Alliance Pharmaceutical Corp.) emulsions on radiosensitivity, tumour relative perfusion and oxygenation was studied using EMT6 tumours in nude mice. Perflubron (2-15 ml/kg) emulsion was injected. The mice inhaled carbogen for 30 min and 60 min prior to irradiation. The radiosensitizing effect of the 90% w/v emulsion was maximal at 4 ml/kg. The tumour relative perfusion diminished after injection of both 100% and 90% w/v emulsions in carbogen-breathing mice at a dose of 15 ml/kg. This drop could explain the lack of efficiency of these treatments at this high concentration. Lastly, tumour oxygenation was increased after administration of perflubron emulsion plus carbogen. PMID- 8356227 TI - Recurrent endometrial adenocarcinoma after surgery alone: prognostic factors and treatment. AB - Twenty-six patients with a local and/or regional relapse of a previously surgically treated adenocarcinoma of the endometrium were referred to the Dr. Daniel den Hoed Cancer Center (DDHCC) in Rotterdam, The Netherlands between 1965 and 1985 for external radiotherapy (ERT) and/or brachytherapy (BT). The 5-year overall survival was 44%. Tumour volume seemed to be an important prognostic factor in locoregional control; 1 out of 17 patients with tumour sizes smaller than or equal to 4 cm relapsed locoregionally, while in 3 out of 9 patients with tumour sizes of more than 4 cm a locoregional recurrence developed. Another important finding is the impact of RT on treatment outcome: none of the 16 patients treated with a combination of ERT and BT failed locoregionally, while 4 out of 10 patients treated with either ERT or BT relapsed. PMID- 8356228 TI - Development of a computer-controlled moving bar (CCMB) conformal technique for neck irradiation. AB - The development of an original conformal technique for neck cancer is in progress in our Institute. This technique uses a computer-controlled moving bar (CCMB): a portion of a blocking bar rotates during the rotation of the gantry in a 2 pi arc field in order to shield the spinal cord over the whole irradiated volume. This technique should solve in a relatively simple way some problems for different clinical situations when cervical node irradiation is required together with the primary tumor. The technique has been tested in an acrylic cylindrical phantom and in the humanoid RANDO phantom for two different irradiation conditions (neck completely bent and partially aligned). PMID- 8356229 TI - Hormonal abnormalities in survivors of primary brain tumours. PMID- 8356230 TI - Using the LQ model in the clinic: definition of normalized total doses. PMID- 8356231 TI - The time variable dose-rate in HDR stepping source brachytherapy. PMID- 8356232 TI - Use of micronuclei formation following graded doses of radiation as a marker for the intrinsic sensitivity of tumors in vivo. PMID- 8356233 TI - Gamma knife radiosurgery for acoustic tumors: multivariate analysis of four year results. AB - In order to evaluate the results of radiosurgery for acoustic tumors and to identify optimum treatment parameters, an analysis of tumor control, as well as incidences of hearing loss, facial and trigeminal neuropathies was undertaken. Between August 1987 and August 1991, 134 patients with 136 acoustic tumors received stereotactic gamma knife radiosurgery at the University of Pittsburgh. Median follow-up was 24 months (range: 6-56 months). Tumor volumes ranged from 0.10 to 17.00 cm3 (median = 2.75 cm3). From one to ten isocenters were utilized per tumor treated (median = 3). Minimum tumor doses varied from 12 to 20 Gy (median = 17 Gy). The 4-year actuarial tumor control rate was 89.2 +/- 6.0%. Some degree of hearing (by pure tone audiometry) was preserved in 71.0 +/- 4.4% of patients. The actuarial rates for preservation of either pretreatment hearing level or useful hearing were 34.4 +/- 6.6% and 35.1 +/- 97% respectively. Respectively, the actuarial incidences of postradiosurgery facial and trigeminal neuropathies were 29.0 +/- 4.4% and 32.9 +/- 4.5%, respectively. No significant factors affecting tumor control were identified. Multivariate analysis identified a significantly increased risk of hearing loss in patients with neurofibromatosis (p = 0.0003) as well as decreased risks of facial and trigeminal neuropathies with both decreasing tumor diameter (p = 0.001) and increasing number of isocenters treated (p = 0.003). Radiosurgery is a safe and effective treatment for acoustic neuromas with acceptable morbidity that may be lowered by the use of multiple isocenter treatment techniques and by earlier treatment of small tumors. PMID- 8356234 TI - Non-Hodgkin's lymphoma of the testis. AB - Primary non-Hodgkin's lymphoma of the testis is rare. From 1976 to 1989 32 patients have been registered with the British National Lymphoma Investigation and two with the Institute of Urology. All 34 patients had disease of high grade histology (BNLI) although in four patients there were some areas with features similar to those described in lymphomas of Mucosal Associated Lymphoid Tissue (MALT). Twenty-three of 34 (67.5%) patients had early stage disease (I/II); 17/34 (50%) achieved complete remission from their initial treatment, and the relapse free survival of these patients was 66% at 5 years. The disease-free survival for the 34 patients as a whole was 33% and their overall survival 39% at 5 years. The life expectancy for those presenting with advanced (stage III/IV) disease was very poor (median survival 9 months) with a low complete remission rate from chemotherapy. The salvage rate from recurrent disease (17%) was poor. Bilateral testicular involvement (18%) and a high rate of central nervous system disease (21%) occurred in the series, and two patients were HIV positive. Stage at presentation was the most important prognostic factor. PMID- 8356235 TI - The present controversial approach to the diagnosis and treatment of prostatic carcinoma. PMID- 8356236 TI - Clinical examination, radiology and markers in the follow-up of prostatic carcinoma. PMID- 8356237 TI - US, CT, MR imaging and radiology in the diagnosis and staging of prostatic carcinoma. PMID- 8356238 TI - Prostatic carcinoma: histopathologic classification, grading, receptors and markers. PMID- 8356239 TI - External beam radiotherapy in the treatment of prostatic carcinoma: technical procedures. PMID- 8356240 TI - Brachytherapy in prostatic carcinoma: technical considerations. PMID- 8356242 TI - Indications and results of radiotherapy in prostatic carcinoma. PMID- 8356241 TI - New 125I dosimetry in prostatic brachytherapy planning. PMID- 8356243 TI - External or interstitial radiotherapy: what indications for the management of prostatic carcinoma? PMID- 8356244 TI - The role of chemotherapy in the treatment of prostatic carcinoma. PMID- 8356245 TI - The role of hormonal therapy in the treatment of prostatic carcinoma. PMID- 8356246 TI - Do antineutrophil cytoplasmic autoantibodies cause Wegener's granulomatosis and other forms of necrotizing vasculitis? AB - The in vitro experimental observations support the theoretical pathogenic scenario depicted in Figure 14. A similar scenario could be portrayed for monocytes. ANCA in the circulation are unable to interact with unprimed neutrophils because the target antigens are within the cytoplasm (Fig. 14A). Synergistic priming of neutrophils, e.g., by an infection, causes small amounts of target antigens to be released at the cell surface (Fig. 14B) where they can interact with ANCA (Fig. 14C). ANCA-activated neutrophils then adhere to endothelial cells via adhesion molecule interactions that may require prior priming of the endothelial cells (Fig. 14C). These activated and adherent neutrophils then injure endothelial cells (and eventually underlying vessel wall structures) by releasing granule enzymes and toxic oxygen metabolites (Fig. 14D). Although many research groups throughout the world have been attempting to create an animal model of ANCA-induced disease based on the theoretical paradigm proposed in Figure 14, as well as on other paradigms, no one has reported complete success. Until this is accomplished, the role of ANCA in the pathogenesis of Wegener's granulomatosis and other forms of ANCA-associated vasculitides will remain conjectural. PMID- 8356248 TI - What is the natural history of rheumatoid arthritis? AB - Analyses of the natural history of RA, recognizing that all patients receive therapies, indicate the following: 1. Classification criteria for RA identify individuals with (at least) three different types of pathogenetic processes and long-term outcomes; most patients seen in clinical settings have progressive disease. 2. Results of therapies documented to be efficacious in clinical trials are not applicable to the long-term course of RA, in part due to patient selection and the short-time frame of observation in clinical trials; most therapies for RA are not effective in most patients over long periods. 3. Over periods of 10 years or longer, most patients with RA experience radiographic progression and severe functional declines, and work disability is seen in 60% of patients after 10 years of disease. 4. Mortality rates are increased in patients with RA, although RA is generally not listed on death certificates. 5. Individual patients with RA who are at risk for early mortality may be identified through clinical markers, including many involved joints, comorbid cardiovascular disease, and poor functional status according to questionnaires and physical measures. 6. Patient behaviors and lifestyles identified through formal educational level as a marker appear of great importance in the prevalence, morbidity, and mortality of RA. PMID- 8356247 TI - Do nonimmunologically mediated pathways play a role in the pathogenesis of rheumatoid arthritis? AB - The association between elevated serum rheumatoid factor and rheumatoid arthritis (RA) has been confirmed repeatedly and interpreted as strong evidence for an immunologic basis for the disease. In recent years, considerable additional evidence supporting this view has been obtained, strongly suggesting a role for CD4+ T cells in the pathogenesis of RA. An alternative view has also gained support, however. Based on studies of animal models and of RA itself, several lines of evidence have emerged that indicate that nonimmunologic pathways are operative in established RA. These observations have fostered the hypothesis that the evolution of RA may be associated with the emergence of non-T-cell-dependent autonomous pathways that dominate the latter stages of the disease. PMID- 8356249 TI - The interplay of nature versus nurture in predisposition to the rheumatic diseases. AB - The revolution in microbiology and genetics that has transpired in the past few years has brought fresh debate in the question of the relative contributions of nature and nurture in susceptibility to the rheumatic diseases. For nature, a variety of immunologically relevant genes have been identified whose presence has been shown to be associated either with an increased risk for certain diseases or for complications or subsets thereof. For nurture, the role of infectious agents in disease triggering and modification has been found. PMID- 8356250 TI - The need for aggressive therapy of rheumatoid arthritis. AB - We are on the threshold of a new era in the treatment of RA if we learn from the experience of the past and utilize new techniques and therapeutic modalities that the future will bring. New strategies and treatment of RA in the future will need to include earlier recognition of progressive disease, earlier interventions, new preparations for use in therapeutic armamentarium, combinations of agents, and monitoring of long-term outcomes to assess results over 5 to 10 years. There is always concern about new therapies and strategies. As noted by Huskisson, however, "In the absence of knowledge about the cause of disease and the mode of action of the drugs, the only way forward is by clinical trials of different preparations. With trial, there is always the risk of error." Our greatest error, however, will be if we ignore lessons from the past, fail to control the inflammatory process early, and continue to spend years writing "doing well" in the charts of patients who become progressively disabled before our eyes. PMID- 8356251 TI - Aggressive therapy does not substantially alter the long-term course of rheumatoid arthritis. So what else is new? AB - A consensus has evolved that there is little evidence supporting the view that the second line agents significantly alter long-term outcomes in rheumatoid arthritis. Consequently, changes in approaches to treatment currently being employed include earlier use of existing second line agents, their use in combinations, and greater use of corticosteroids. Our awareness that our current drugs, at best, fall considerably short of attaining the therapeutic results we would like to achieve causes us to look forward to the development of rationally derived biologic agents with considerable anticipation. PMID- 8356252 TI - The curious case of intramuscular gold. AB - Controlled clinical trials, meta-analysis, and observational studies provide strong evidence of short-term gold efficacy. There is also substantial evidence for the retardation of radiographic abnormality. Although gold therapy is discontinued by most patients within 2 years of onset, a minority of patients sustain important long-term benefit. PMID- 8356253 TI - Should steroids be used in the management of rheumatoid arthritis? PMID- 8356254 TI - Reflections on unproven remedies. AB - The use of unproven remedies is widespread in the United States. Most rheumatic disease patients, regardless of socioeconomic or educational background, try a number of these. This essay presents a somewhat tolerant view of nontraditional arthritis remedies, which, when considered thoughtfully, may advance our art. PMID- 8356255 TI - Microbial superantigens as etiopathogenic agents in autoimmunity. AB - A recently characterized group of immunologically active microbial products, termed superantigens, may provide the etiopathogenic link between antecedent infection and the subsequent development of autoimmunity in the genetically susceptible host. In this article, the authors review the cellular interactions that underlie autoimmune disease and emphasize the central role played by T lymphocytes. Based on the unique properties of the superantigen and data derived from experimental animal models and clinical studies of human autoimmune disease, a hypothesis that these molecules could trigger both systemic and organ-specific autoimmunity was developed. PMID- 8356256 TI - What is lupus? What is not lupus? AB - Present understanding suggests that lupus reflects a spectrum of syndromes that share many clinical, inflammatory, and immunologic features. Those patients not fulfilling criteria for systemic lupus erythematosus (SLE) do not seem to evolve frequently to classic SLE, tend to have a good prognosis, and may be managed conservatively. This is important for clinical management. Whether this pertains to etiopathogenesis is speculative and will await information not yet available. PMID- 8356257 TI - Which patients with antiphospholipid antibody should be treated and how? AB - The tests for antiphospholipid antibody are relatively crude but usable. Asymptomatic persons with incidentally discovered antiphospholipid antibody do not need treatment. Those with symptoms are best treated with anticoagulation, but data specifically supporting aspirin, heparin, or warfarin or combinations thereof remain to be generated. High-dose corticosteroid therapy has at best equivocal efficacy and much toxicity and should be used only for lupus activity and not for phenomena of the antiphospholipid antibody syndrome. The roles of low dose corticosteroid therapy, immunosuppressive agents, and other treatments are unknown. PMID- 8356258 TI - Is aggressive therapy effective for lupus? AB - Intravenous cyclophosphamide is an effective form of aggressive therapy for the management of a wide range of serious manifestations of systemic lupus erythematosus. Although it has been best studied in patients with progressive lupus nephritis, recent evidence indicates an important role for this therapy for other clinical lupus indications, particularly acute neurologic diseases. The available comparative data suggest that intravenous cyclophosphamide is far more effective than intensive corticosteroid therapies, including conventional high dose oral therapy as well as bolus intravenous therapy. Differences in efficacy compared with oral regimens of cyclophosphamide or azathioprine are less clear, although clinical experience would seem to suggest that intravenous cyclophosphamide has a more rapid onset of action clinically than low-dose oral therapies. Finally, the toxicity profile of intravenous cyclophosphamide compares favorably with other aggressive approaches to drug management and does not pose an unacceptable risk. The future impact of several current investigational therapies remains to be defined. PMID- 8356259 TI - Is "aggressive" therapy necessary for systemic lupus erythematosus? AB - Much of the initial attention in therapeutic studies for systemic lupus erythematosus (SLE) has justifiably been focused on the severe forms of the disease such as diffuse proliferative glomerulonephritis or central nervous system manifestations. Unfortunately, to all forms of SLE, thereby submitting patients with more benign variants of lupus have been submitted to aggressive, toxic, and probably unnecessary treatments. The thesis of this article is that aggressive therapy is not always necessary for SLE. PMID- 8356261 TI - Fibromyalgia and the rheumatisms. Common sense and sensibility. AB - Chronic musculoskeletal pain syndromes are common problems, but the etiology, pathogenesis, and pathology of many of them are very poorly understood. Because the currently used nomenclature suggests an understanding that we do not have, I propose that names like "myofascial pain," "tension myalgia," and "FM" be abandoned in favor of the more indefinite (but more honest) terms like "regional" and "generalized rheumatism." No matter what we rheumatologists call it, however, the condition of chronic generalized musculoskeletal pain probably is only one part of an even more generalized condition that includes IBS, chronic headaches, regional migratory numbness, TMJ syndrome, and a whole host of other somatic pain syndromes. The same patients end up seeing many specialists who themselves feel frustrated with the labels at their disposal, and these specialists end up resembling the blind men confronting the elephant. In this regard, the new ACR criteria for the diagnosis of fibrositis, by emphasizing tenderness and ignoring the presence of these other syndromes, are too circumscribed and represent a step backward in our attempts to understand. Although the chronic rheumatisms are problems difficult to manage and frustrating for both the patient and the physician, when patience can be applied and confidence achieved, a positive relationship can result and the patient can be helped. PMID- 8356260 TI - Should nonsteroidal anti-inflammatory drugs be used to treat osteoarthritis? AB - Millions of individuals with osteoarthritis have experienced relief of joint pain and improvement in mobility as a result of taking nonsteroidal anti-inflammatory drugs (NSAIDs). These agents are currently considered the drug of choice for treatment of osteoarthritis (OA). Despite their efficacy and nearly universal use in OA, the role of NSAIDs in managing this disorder recently has become controversial. This article reviews the issues that lie at the heart of the problem. PMID- 8356262 TI - Lyme disease: testing and treatment. Who should be tested and treated for Lyme disease and how? AB - LD can mimic a number of other disease, and vice versa. It is imperative that clinicians understand LD and be able to use serologic diagnostic techniques appropriately. LD is not a diagnosis that can be made on the basis of serologic testing. By this is meant that vague symptoms plus a positive serologic test do not assure that the patient has LD. On the other hand, a patient with ECM or other manifestations of LD may still be seronegative. In addition, therapy for LD must be tailored to the clinical problems of the individual patient. Especially in patients with chronic or persisting complaints, it is important to be precise in making the correct diagnosis and in understanding the underlying pathogenetic mechanisms at work so that an appropriate and ultimately successful therapeutic plan can be made. PMID- 8356263 TI - Is measurement of bone density useful? AB - Bone density testing is safe, accurate, and useful. Specific clinical indications and the types of equipment available to assess them are reviewed. A positive effect on the practice of a clinical rheumatologist with resultant improved patient care appears likely in light of the information available. PMID- 8356264 TI - Extraosseous Tc-99m MDP uptake: a pathophysiologic approach. AB - Scintigraphy with technetium-99m methylene diphosphonate (MDP) delineates a wide spectrum of nonosseous disorders. Neoplastic, hormonal, inflammatory, ischemic, traumatic, excretory, and artifactual entities demonstrate abnormal soft-tissue uptake of Tc-99m MDP. Mechanisms leading to increased extraosseous Tc-99m MDP uptake include extracellular fluid expansion, enhanced regional vascularity and permeability, and elevated tissue calcium concentration. The composition of the calcium deposition and the presence of other metallic ions (eg, iron and magnesium) are important. Soft-tissue Tc-99m MDP uptake is seen in benign (tumoral calcinosis, myositis ossificans) and malignant (sarcomas, adenocarcinomas, metastases) neoplastic entities. Hormonal disturbances in calcium metabolism, especially in hyperparathyroidism, can lead to metastatic calcification, visualized with Tc-99m MDP scintigraphy. Tissue damage from inflammation, infection, or physical trauma results in localized hyperemia, edema, or calcium (and hemosiderin) deposition based on their pathophysiologic characteristics. Urinary tract obstruction, anomalies, or dysfunction are demonstrated by Tc-99m MDP imaging. Common artifacts are related to faulty radiopharmaceutical preparation, Tc-99m MDP administration, and imaging technique. Recognition of these modes of extraskeletal Tc-99m MDP uptake can enhance the diagnostic value of bone scintigraphy. PMID- 8356265 TI - CT in abdominal and pelvic trauma. AB - Computed tomography (CT) is valuable in the evaluation of the abdomen and pelvis in victims of blunt trauma and stab wounds to the back if their condition is stable or if results of their physical examination are unreliable (eg, due to altered mental status). The appearance of blood at CT depends on window width, hematocrit, physical state of blood, use of intravenous contrast material, and attenuation of adjacent organs. Rapid infusion of contrast material improves visualization of hematoma. CT is most useful in evaluating injuries to the spleen, liver, pancreas, kidney, duodenum, and small and large bowel. Although CT can be accurate in demonstrating lacerations and hematoma, radiologists must beware of pitfalls in the CT diagnosis of splenic injuries (normal lobulation or cleft within the spleen, elongation of the left hepatic lobe, adjacent unopacified bowel loop, previous splenic infarct), hepatic injuries (beam hardening artifact from adjacent ribs, air-contrast level in the stomach), and pancreatic injuries (streak artifacts from nasogastric tubes, folding of the pancreas, misinterpretation of adjacent structures, pancreatic contusion or hematoma, intrinsic elasticity of the pancreas). Delayed scanning or scanning with slow infusion rates may also obscure hematoma. Knowledge of the various appearances of the posttraumatic abdomen and pelvis on CT scans is essential for prompt and effective treatment of patients. PMID- 8356266 TI - Imaging of pregnancy-related complications. AB - Thirty-six cases of pregnancy-related complications were studied with plain radiography, ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging alone or in combination. Among the complications diagnosed with these various techniques were venous thromboembolic disorders, deep vein thrombosis, ovarian vein thrombosis, endometritis and pyometra, HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelet counts), hepatic hematoma and rupture, fatty liver, uterine rupture, various hematomas and a foreign body, tubo-ovarian abscess, cerebral venous thrombosis, cerebral ischemia, and cerebral edema. Prompt detection and appropriate management of many of these complications could result in decreased maternal and fetal mortality and morbidity. Although US should be considered first because it can be performed bedside, does not require use of ionizing radiation, and is cost-effective, CT is superior in demonstrating the extent of the abnormality and MR imaging is best for detection of neurologic complications of pregnancy. The radiologist should select the best available method and tailor the examination according to the presumptive clinical diagnosis and the individual problem to be solved. PMID- 8356268 TI - Imaging of complications of lung transplantation. AB - With the increasing number and improved survival of lung transplant recipients, radiologists should be aware of the imaging features of lung transplants and the associated complications. Reimplantation response, a noncardiogenic pulmonary edema seen 48 hours after transplantation that subsequently resolves, varies in appearance from a mild perihilar haze to a dense consolidation in the perihilar areas and lung bases. A late complication of omentopexy (used to prevent bronchial dehiscence) is herniation of abdominal contents through the diaphragmatic incision into the thorax. Extrabronchial air collections are a radiologic manifestation of anastomotic dehiscence. Stricture formation that compromises the bronchial lumina is usually visible with plain radiography, but computed tomography can aid in the evaluation. Acute rejection is evident radiographically as new or increasing pleural effusions, septal lines, subpleural edema, peribronchial cuffing, and air-space disease, without increase in cardiac size. Radiographic features of chronic rejection include both increased and diminished lung volumes, central and peripheral bronchiectasis, localized air space disease, partial lobar atelectasis, thin linear irregular areas of increased opacity, pleural thickening, and diminished peripheral lung markings. Infection is frequently seen, especially gram-negative pneumonias, with fewer occurrences of cytomegalovirus infection, candidiasis, and invasive aspergillosis. PMID- 8356267 TI - Pattern recognition of the pulmonary manifestations of AIDS on CT scans. AB - More than 50% of patients with acquired immunodeficiency syndrome (AIDS) develop pulmonary disease during the course of their illness. The authors reviewed 96 computed tomographic (CT) scans of patients with AIDS in an attempt to describe disease entities by the patterns seen on the scans. Such patterns included isolated ground-glass and interstitial infiltrates, which are suggestive of Pneumocystis carinii pneumonia (PCP). If pleural effusions or parenchymal nodules are also present, AIDS-related lymphoma (ARL) or Kaposi sarcoma (KS) is more likely. Although diffuse alveolar infiltrates are most commonly present in PCP, a segmental alveolar infiltrate is suggestive of a bacterial pneumonia, especially when associated with cavitation or ipsilateral pleural effusion. Well-defined nodules are typical for ARL, whereas ill-defined nodules are more commonly suggestive of KS. Accompanying adenopathy or effusion with nodules further suggests ARL. Different combinations of parenchymal, nodular, and pleural abnormalities may be suggestive for additional diagnoses, including Mycobacterium tuberculosis, M avium-intracellulare, and Cryptococcus neoformans infections and human immunodeficiency virus adenopathy. The authors believe that a specific pattern of involvement can help suggest a likely diagnosis in many instances. PMID- 8356269 TI - Spinal fixation. Part 3. Complications of spinal instrumentation. AB - Spinal fixation devices can be used to form a rigid construct with the spine to replace bone, restore alignment, maintain position, and prevent motion in the treatment of fractures, degenerative disease, neoplasm, and congenital deformities. Because most spinal constructs will eventually fail if bone fusion does not occur, bone graft material is often used along with the implant to promote fusion. Conventional radiographs, obtained in two projections, remain the mainstay of implant evaluation, demonstrating the position of the spinal elements, hardware, graft material, and evidence of complication. Possible complications connected with use of fixation devices include intraoperative soft tissue injuries, postoperative hematomas, and infection. The components (through incorrect use, malpositioning at surgery, and later dislodgment or fracture) may also contribute to complications such as instability; failure of fusion; or pain, with possible resultant neurologic damage. Bone graft material can migrate or hypertrophy, resulting in impingement on the spinal canal or neural foramen. Radiologists should be familiar with the various spinal fixation devices and techniques to better identify evolving complications. PMID- 8356271 TI - Preservation of augmented breasts in patients with breast cancer. AB - It is not uncommon for a patient who has previously undergone breast augmentation to be diagnosed with breast cancer. The options available to such a patient are a modified radical mastectomy and breast conservation treatment. If the patient chooses breast conservation treatment, the concerns that need to be addressed are whether the breast prosthesis should be removed before irradiation and whether the presence of the prosthesis would impair local control of the tumor or cosmetic results. This article presents the feasibility of breast conservation treatment without impairing the augmentation. Five patients underwent lumpectomy, perioperative placement of interstitial catheters in the tumor bed for immediate postoperative boost brachytherapy, and external beam irradiation to the entire breast. Results of follow-up examinations for a median of 60 months revealed successful local control and satisfactory cosmetic results. No long-term effects of radiation therapy on the breast prostheses have been observed. Thus, it seems feasible to conserve the breast and the augmentation with limited surgical resection and radiation therapy, including an immediate interstitial boost. PMID- 8356270 TI - Painful conditions affecting the first metatarsal sesamoid bones. AB - The sesamoid bones of the first metatarsal exhibit a special anatomic configuration, enveloped by the tendons of the flexor hallucis brevis and lying within the capsule of the first metatarsophalangeal joint. Painful conditions of the hallux sesamoid bones are many and include congenital, traumatic, arthritic, infectious, and ischemic conditions. Because of the complex anatomy and the numerous pain-sensitive structures in the region of the first metatarsophalangeal joint, a differential diagnosis can be challenging. The imaging examination should always begin with conventional radiography, including special axial and lateromedial views of the sesamoid bones. In cases in which results of routine radiography are inconclusive, scintigraphy, conventional or computed tomography, xeroradiography, or magnetic resonance imaging can be used. A thorough understanding of the anatomy; pathophysiology; and clinical, laboratory, and imaging findings is often helpful in the establishment of a diagnosis and management plan for painful conditions of the hallux sesamoid bones. PMID- 8356272 TI - Spiculated lesions of the breast: mammographic-pathologic correlation. AB - Spiculated breast lesions may be caused by both benign and malignant processes, including sclerosing adenosis, postsurgical scar, radial scar, tuberculosis (rare), posttraumatic oil cysts, infiltrating ductal carcinoma, ductal carcinoma in situ (rare), infiltrating lobular carcinoma, and tubular carcinoma. Mammographically, such lesions are often similar, and only some can be differentiated on the basis of morphologic characteristics. Although microcalcifications are often associated with breast carcinoma, not all spiculated lesions with microcalcifications are malignant. Sclerosing adenosis occurs with punctate microcalcifications, but the lesion often has a radiolucent center, compared with the opaque center generally found in malignant spiculated lesions. Radial scar may occasionally occur with microcalcifications and usually has a radiolucent center, but the latter is not a reliable criterion for differentiation from carcinoma. The spicules of benign lesions are often caused by fibrous tissue, lipid-filled spaces surrounded by histiocytes, or sclerotic stroma, whereas the spicules of malignant lesions are due to tumor infiltration, desmoplastic response, or periductal fibrosis. Mammography alone is frequently not reliable for making the specific diagnosis. Clinical breast examination, additional mammographic views, and needle or surgical biopsy are often required. PMID- 8356273 TI - From the archives of the AFIP. Extraskeletal osseous and cartilaginous tumors of the extremities. AB - Extraskeletal osseous and cartilaginous tumors and tumorlike conditions of the extremities can often be differentiated radiologically; for those that cannot, knowledge of the spectrum of lesions will allow a suitably ordered differential diagnosis. Of the osseous lesions--myositis ossificans, fibro-osseous pseudotumor, fibrodysplasia ossificans progressiva, soft-tissue osteoma, and extraskeletal osteosarcoma--all but myositis ossificans are relatively rare. Myositis ossificans has a distinct mineralization pattern that can be observed radiologically as a peripheral rim of lamellar bone. Fibro-osseous pseudotumor typically occurs in the digits of the hand and lacks the well-defined zoning pattern of myositis ossificans. The cartilaginous entities include the true tumors, soft-tissue chondroma and extraskeletal chondrosarcoma, and the tumorlike process, synovial osteochondromatosis. The tumors are relatively rare; synovial osteochondromatosis commonly affects middle-aged men, especially in the knee, and is associated with osteoarthritis. The differential diagnosis for these extraskeletal osseous and cartilaginous lesions includes soft-tissue sarcoma, benign mesenchymoma, malignant mesenchymoma (rare), calcified tophi in gout, melorheostosis (rare), pilomatricoma (rare), and tumoral calcinosis (rare). PMID- 8356274 TI - Advances in clinical neuroimaging: functional MR imaging techniques. PMID- 8356275 TI - Interventional MR imaging. PMID- 8356276 TI - MR imaging of the breast: technical approach and clinical experience. PMID- 8356277 TI - Current trends in MR imaging of the female pelvis. PMID- 8356278 TI - MR angiography of the peripheral vasculature. PMID- 8356279 TI - Computer-aided instruction for radiologic education. PMID- 8356281 TI - Medical records: mind what you say. PMID- 8356280 TI - Searching on-line data bases. PMID- 8356282 TI - Single-element transducers. PMID- 8356283 TI - Pediatric case of the day. Ewing sarcoma of the thumb with multiple metastases. PMID- 8356284 TI - Ultrasound case of the day. Combined iatrogenic CFA pseudoaneurysm and CFA-CFV arteriovenous fistula. PMID- 8356285 TI - General case of the day. Enterolith in a blind pouch (blind pouch syndrome secondary to side-to-side enteroanastomosis). PMID- 8356286 TI - [Infection and systemic lupus erythematosus: analysis of a series of 145 patients]. AB - Systemic lupus erythematosus (SEL) is a chronic inflammatory disease, which often requires corticosteroid treatment, being infection a common cause of both morbidity and mortality. We report the infectious episodes from 145 SLE patients revisited through 1975-1991, with a 6.8 years mean follow-up period. The relationship between each episode and several variables, especially corticosteroid treatment a month before the infectious episode, was analyzed. Forty two infections were diagnosed in 32 patients (22.06%). A significant increase in the number of infections among SLE patients with daily corticosteroids treatment was observed with respect to that of SLE patients with alternate day treatment (p < 0.001). The administration corticosteroids in alternate day form, if possible, can decrease the infection incidence in SLE patients. PMID- 8356287 TI - [Cancer mortality in women from Cadiz. 1975-1983]. AB - Both in Spain and in the rest of industrialized countries, cancer is the second caused mortality in accordance with its incidence. Respect to the different Autonomous Communities, Andalucia is that where men are at most unfavorable situation, and women are within the most unfavored. Out of all the Provinces which constituted this Community, mainly Cadiz attracted attention by its systematically and constantly growing rates of that tumors present in the most common localizations. The aim of the present work is to study, by means of death certificate dates, the mortality rate of women from Cadiz between 1975-1983. Mortality rate was 104.08 decease per 100,000 inhabitants. The cut off rate of female population older than 40 years was 287.77. The temporal trend of women cancer in our ambient was studied comparing the mortality rates with the incidence rates from some Spanish Populational-Based Cancer Registers (Granada, Murcia, Tarragona and Navarra). We conclude that in Cadiz Province there is a higher number of women decreased by cancer, mainly by liver cancers. PMID- 8356288 TI - [Liver disease in patients with human immunodeficiency virus infection. Study of 100 biopsies]. AB - Human immunodeficiency virus (HIV)-related liver disease is frequently diagnosed. We report a study about 100 liver biopsy samples (LB) in patients with HIV infection. The aim of the study has been to analyze the liver biopsy yield when a systemic disease (group A) or a chronic liver disease (group B) are suspected. Tuberculosis, all of them disseminated, was the most common finding in group A biopsy samples, and a 81% yield was obtained. Chronic active hepatitis was the most common finding group B, and profitability reached 90%. We conclude that LB is the elective method to diagnose systemic disease, in patients previously selected according to their clinical findings, and that final diagnoses and safe. PMID- 8356289 TI - [Scleromyxedema associated with myopathy]. AB - We describe a 45 year-old man, with scleromyxedema associated to systemic manifestations, including myopathy. After 6 years of dermatologic manifestations, muscular weakness, with proximal predominance resulting in incapacity, was established. Corticosteroids plus cyclophosphamide treatment suppressed muscular symptomatology, and a second biopsy was normal. The common association between scleromyxedema and myopathy and other systemic alterations suggest that this entity should probably be considered as a systemic disease instead as a skin disease. PMID- 8356290 TI - [Evolution of the emergency consultations in patients with human immunodeficiency virus infection in various levels of medical care in an urban area of Barcelona]. AB - Medical emergencies involving patients with Human Immunodeficiency Virus (HIV) infection comprise an increasing number of the total hospitalary consults and contribute to their overflow. In order to evaluate possible alternative solutions to this problem, we performed a retrospective study of urgent medical consults by HIV patients at three different levels of medical care (primary assistance, extrahospitalary and hospitalary emergencies centers) all included in the same urban area of Barcelona. We demonstrated a growing excess in hospitalary emergencies, with high requirements of complementary explorations and hospitalary admittances. In the extrahospitalary emergency center, we can observe a progressive increasing of emergency consults, but still reasonable in number and adequate to the real possibilities of the center. At primary care level, HIV patients consulted because of less severe reasons. We conclude that a possible solution in order to decrease the assistance requirements in the hospitalary emergencies level could be to try to attend these patients in emergency extrahospitalary centers. These centers should be technically provided and with a close relationship both with the primary assistance care level and with the reference hospital. PMID- 8356291 TI - [Intra-abdominal paraganglioma: clinical, functional, structural, and immunohistochemical study of an exceptional case]. AB - Paragangliomas are tumors, derived from paraganglionary system, able to synthesize and to liberate substances with neuroregulatory activity. They are rare, mainly in the neck located, difficult to anatomo-pathologic diagnose, and of poor prognosis. They may present as space-occupying lesions or as secondary syndromes due to the liberation of biologically active substances. Whenever it is possible, surgical excision is the treatment of choice. Nor chemotherapy, nor immunomodulators, like alpha-2b-interferon, have provided satisfactory results. A 57 year-old man, with a non-surgical paraganglioma characterized by abdominal mass associated with liver and bone metastasis, is presented. The rarity of the intra-abdominal presentation, the image study findings, the histopathological and immunohistochemical examinations, and the evolution after alpha-2b-interferon therapy are analyzed. PMID- 8356292 TI - [Malignant lumbosciatic syndrome. Report of 21 cases with vertebral metastases]. AB - We describe twenty one cases of tumoral metastasis on the vertebral column simulating initially discal herniation. All of them presented sciatica as a primary clinical manifestation of the malignant tumor. We describe here the differential diagnosis with other pathologies and the different outcome, like the poor response to regular treatment, alteration of the normal status, and alteration of the laboratory data. The radiologic findings and the laboratory abnormalities found in the emergency analysis should induce us to do more complete studies of the patient aimed to identify an underlying tumoral pathology. PMID- 8356293 TI - [Pharmacological knowledge among general physicians]. AB - We inquired to 200 physicians about the 50 pharmaceutical products most dispensed in Seville during 1989. The most significative results were: 68.5% of the inquired answered the questionnaire. 98.5% knew the product, but only 80.3% prescribed it. The principal sources of information to know the drug were books and scientific journals (67.3%), followed by detailers (62%). 86.1% knew the composition of the product, and 94.9% knew its indications. 71.5% described the side effects, 66.4% the contraindications, and 25.5% the interactions with other drugs. Only 56.9% mentioned a therapeutic alternative. PMID- 8356294 TI - [Cancer of unknown origin: diagnostic and therapeutic yield]. AB - Patients with carcinoma of unknown origin represents at least 5% on the total neoplastic patients. A review of the main metastatic locations and the different histological types has been done; giving special attention to the most frequent primitive neoplasms. Diagnostic yield in this type of cancer is emphasized, since many times, it is advisable to limit the number of explorations directed to find the primary tumor, as they decrease patient quality of life while no profit is obtained from the knowledge of the primary tumor, for most of the patients. However, this must not drive us to the opposite end: diagnostic and therapeutic nihilism. We have to rule out, in a reasonable way, certain types of tumors which have an useful treatment even in advanced phases (oat all carcinoma, germinal neoplasms, lymphomas). PMID- 8356295 TI - [Muscular tumors of the digestive tract]. AB - We report the experience of the General Surgery Service of Segovia General Hospital. In a 15-years-period (1976-1991), we have cared for 32 patients with muscular tumors of the gastrointestinal tract, including 22 leiomyomas and 11 leiomyosarcomas. These tumors were localized in stomach (46.8%), small intestine (40.6%), esophagus (9.3%) and colon-rectum (3.1%). A histologic study was developed on the basis of the mitosis number in 10 high power fields. Clinical manifestations, histological dates, treatment, and prognosis factors, outstanding the histological grade, size lesser than 10 cm, and tumor origin localization, are reviewed. PMID- 8356296 TI - [Hypersensitivity to aromatic anticonvulsive agents. Report of 2 cases]. PMID- 8356297 TI - [Pentamidine-induced diabetes mellitus]. PMID- 8356298 TI - [Incidentalomas and serendipity]. PMID- 8356299 TI - [Adrenal gland incidentalomas smaller than 6 cm and their gammagraphic imaging diagnosis]. PMID- 8356300 TI - [The therapy of hypertension]. PMID- 8356301 TI - [Good health]. PMID- 8356302 TI - [The relations between atrial natriuretic factor release and adrenergic activation in hypertrophic cardiomyopathy]. AB - Atrial natriuretic factor (ANF) is a potent natriuretic and vasoactive (vasorelaxant) peptide localized in the secretory-like atrial specific granules. The main peptide in this storage granules is the 126 amino acid proatrial natriuretic peptide, but the principal circulating form in human plasma is the 28 amino acid, alpha-human natriuretic peptide. Animal and in vitro studies have suggested that ANF modulates autonomic circulatory control, probably with a dose dependent mechanism. Moreover, recent human studies have resulted contradictory. In particular, it is still unclear if high circulating levels of ANF, which are present in congestive heart diseases constantly, may be correlated with sympathetic nervous system activity in man. Previously we have shown that in congestive diseases there is a relation between ANF and catecholamine secretion. From these basis, the aim of this study was to investigate on the pathophysiological relations between atrial natriuretic factor (ANF) release and adrenergic activation in patients with obstructive hypertrophic cardiomyopathy (n = 6) and non obstructive hypertrophic cardiomyopathy (n = 4). Sympathetic activation in physiologic way was induced by cycloergometer sub-maximal exercise. Then specimens of venous blood were achieved for plasma determination of ANF and catecholamines pre- and post-exercise. Results have shown that in obstructive hypertrophic cardiomyopathy patients basal levels of ANF and catecholamines were higher than levels of these parameters in non obstructive hypertrophic cardiomyopathy patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356303 TI - Oxidative burst and lysosomal enzyme release by polymorphonuclear cells in type IIa, type IIb and type IV primary hyperlipoproteinaemia. AB - Several findings pint out the occurrence of a strict relationship between lipoproteins and immunoresponsiveness. In this regard, in vitro lipoproteins pretreatment of mononuclear cell suspensions leads to an inhibition of Natural Killer (NK) cytotoxicity or T- and B-mediated immune functions. These results have an in vivo counterpart, since an impairment of either T-driven B cell polyclonal differentiation or phagocyte chemotaxis, phagocytosis and killing has been shown in patients with type IIa and type IIb primary hyperlipoproteinaemia. On the contrary, these activities fall within normal range in type IV hyperlipoproteinaemic subjects. To further address the potential role of polymorphonuclear cells (PMN) in atherosclerotic process, in the present report PMN-mediated superoxide anion (O2-) generation, hydrogen peroxide (H2O2) production, beta-glucuronidase and myeloperoxidase release have been assessed in similar groups of patients. Results provide a clearcut evidence for a significant enhancement of oxidative metabolism by either suspended or adherent to plastic PMN in type IIa primary hyperlipoproteinaemia only. These data were further confirmed by the observation that the same cell suspensions exhibit a significant increase of H2O2 generation and/or beta-glucuronidase and myeloperoxidase release. By contrast, PMN metabolic pathway in type IIb and type IV patients mimics that observed in healthy individuals. In the light of the well known increase of serum low-density lipoproteins (LDL) in type IIa primary hyperlipoproteinaemia, these findings suggest that also PMN may play an important role in the development of atherosclerosis. The augmented oxidative responsiveness may, in fact, give rise to LDL oxidation, which is in turn responsible for foam cell generation through an exaggerated uptake of oxidized LDL by macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356304 TI - [Chronic kidney failure: dialysis and kidney transplantation. The medicolegal and social considerations]. AB - The authors carried out a research on the social and labour problems of the people affected by chronic renal failure, either on dialysis treatment or already transplanted since two years. It has been given a questionnaire based on questions about the person, the working position, the social insurance situation, the family and personal problems. The results show a good social reinsert and a good recover of the transplanted in opposition of the many problems had by those on dialysis; in particular it has been considered also the problem of the periodic absences from work. It has been also considered the italian law situation regarding the people affected by chronic renal failure in some different social insurance fields. PMID- 8356305 TI - [Atraumatic rupture of the renal pelvis]. PMID- 8356306 TI - [Mastocytosis. A case of urticaria pigmentosa with a systemic malignant evolution]. AB - A case of systemic mastocytosis with a malignant course, started as urticaria pigmentosa in adult age, is reported. The progression from cutaneous to systemic involvement has been marked by increasing hypereosinophilia which can be considered an important sign of adverse prognosis. PMID- 8356308 TI - Impaired growth hormone response to growth hormone releasing hormone in myotonic dystrophy. PMID- 8356307 TI - [Recombinant granulocyte colony-stimulating factor in the long-term treatment of AIDS-related neutropenias]. AB - Neutropenia is a common finding in patients with AIDS or AIDS-related complex (ARC), and limits their survival and therapies. We administered recombinant human granulocyte colony-stimulating factor (rG-CSF) 300 micrograms/day to 15 AIDS patients with severe neutropenia (< 1000/microliters). without discontinuing zidovudine, ganciclovir or other myelosuppressive drugs (e.g. antineoplastic chemotherapy). All patients showed correction of neutropenia and/or limitation of drug myelosuppressive action. Neutrophil count was > 1000/microliters during the whole follow-up (11 months). No patient showed sepsis, opportunistic infections or side effects. These data confirm the efficacy and tolerability of rG-CSF in AIDS-related neutropenia. PMID- 8356309 TI - [The therapy of peripheral obstructive arteriopathies: rational bases]. AB - The authors underline the relations among the anatomical lesion progression, the appearance of the clinical signs (claudicatio) of tissue ischaemia and the thromboembolic event in vascular districts like myocardium and brain, at high morbidity and mortality risk. They widely state the pathogenetic mechanism of the atherosclerotic arterial disease and the compensative mechanisms that may prevent the ischaemic effects of the vascular obstruction. It has been considered the importance of the hemorheologic changes and their influence on the development of the ischaemic syndrome. The therapeutic choice in relation to physiopathologic and hemorheologic events in the peripheral obstructive arterial disease is considered. PMID- 8356310 TI - [Insulin resistance: related clinical syndromes]. AB - The authors, after having defined and listed the pathogenetic mechanisms of insulin resistance, describe the main, more or less frequent, syndromes with accompany this condition, classified on the basis of the prevalent etiology (dismetabolic, disendocrine, genetic, mixed), identifying of each one, when possible, the modes of determining the same insulin resistance. The more frequent diseases, whose common feature is the insulin resistance (obesity, non insulin dependent diabetes mellitus, acanthosis nigricans, polycystic ovarian syndrome) are particularly considered on the basis of recent literature and of personal data. PMID- 8356312 TI - Genetic determinants in carcinogenesis. PMID- 8356311 TI - [Mycoplasmas and mycoplasmosis: the etiopathogenetic problems and nosological, clinical and diagnostic advances]. AB - Authors point out, on the basis of literature and of their own experience, the following aspects of Mycoplasma infections: 1) Genetical and biological progresses, especially related to pathogenetic aspects and diagnostic procedures. 2) Recent clinical and diagnostic findings of M. pneumoniae infections: "bacteria like" pulmonary presentations by mycoplasmas (and, on the contrary, "virus-like" pulmonary presentations by bacteria); atypical kinds of pulmonary presentations by mycoplasmas; role of autoimmunity in extrapulmonary involvement. 3) Relationship among mycoplasmas, immune system and autoimmune diseases, with particular regard to animal models and to the Mycoplasma "superantigen". 4) Appearance of new pathogens and of a new spectrum of Mycoplasma infections: genito-urinary involvement by Ureaplasma urealyticum and by M. Hominis; relationship between Mycoplasma spp. and HIV infection. PMID- 8356313 TI - Dysplastic nevi-dysplastic nevus syndromes: clinical features and genetic aspects. PMID- 8356314 TI - Integrins and melanoma progression. PMID- 8356315 TI - Growth regulation in normal and malignant melanocytes. PMID- 8356316 TI - Transforming growth factor regulation of keratinocyte growth. PMID- 8356317 TI - Keratinocyte carcinogenesis: introduction. PMID- 8356318 TI - Diversity of epithelial skin tumors: thoughts and comments on some basic principles. PMID- 8356319 TI - Cellular and molecular changes during mouse skin tumor progression. PMID- 8356320 TI - Influence of aging and malignant transformation on keratinocyte gene expression. PMID- 8356321 TI - Molecular mechanisms of skin carcinogenesis induced by chemicals and ionizing radiation. PMID- 8356322 TI - Threshold-like dose response of mouse skin cancer induction by repeated beta irradiation and its relevance to radiation-induced human skin cancer. PMID- 8356323 TI - Environmental risk factors for skin cancer. PMID- 8356324 TI - Ultraviolet carcinogenesis: environmental effects of ozone depletion. PMID- 8356325 TI - Experimental ultraviolet carcinogenesis. PMID- 8356326 TI - Xeroderma pigmentosum patients from Germany (the Mannheim XP collection): clinical and biochemical characteristics. PMID- 8356327 TI - The in vitro analysis of biochemical changes relevant to skin carcinogenesis. PMID- 8356328 TI - Positive and negative growth control in multistage skin carcinogenesis. PMID- 8356329 TI - Epithelial stem cells, hair follicles, and tumor formation. PMID- 8356330 TI - The role of endogenous factors in skin carcinogenesis. PMID- 8356332 TI - Skin carcinogenesis: a health problem meets with a scientific challenge concluding remarks and future prospects. PMID- 8356331 TI - In vitro transformation and tumor progression. PMID- 8356333 TI - The skin: initiation and target site of immune responses. PMID- 8356334 TI - Melanocyte carcinogenesis: facts and fancies. PMID- 8356335 TI - The German melanoma registry and environmental risk factors implied. PMID- 8356336 TI - Fair complexion and risk of malignant melanoma of the skin based on experience from the Danish Cancer Registry. AB - Our Danish study shows that many pigmented naevi, a tendency to freckle and light hair colours are significant, important, and independent host factors which increase the risk of development of malignant melanoma of the skin. These results are in line with what has been consistently shown in previous and in more recent case-control studies. Light hair colour may be a measure of light complexion. The finding that individuals with a large number of naevi, a tendency to freckle and a sensitive skin constitute a risk group may be of importance. Such individuals could be warned about signs of early melanoma development and be instructed to avoid excessive sun exposure, especially damaging sunburn, with the aim of reducing melanoma mortality and melanoma incidence, respectively. PMID- 8356337 TI - A new pressure chamber to study the biosynthetic response of articular cartilage to mechanical loading. AB - A prototype chamber was used to apply a precise cyclic or static load on articular cartilage explants under sterile conditions. A variable pressure, pneumatic controller was constructed to power the chamber's air cylinder, capable of applying, with a porous load platen, loads of up to 10 MPa at cycles ranging from 0 to 10 Hz. Pig articular cartilage explants were maintained successfully in this chamber for 2 days under cyclic mechanical loading of 0.5 Hz, 0.5 MPa. Explants remained sterile, viable and metabolically active. Cartilage responded to this load with a decreased synthesis of fibronectin and a small but statistically significant elevation in proteoglycan content. Similar but less extensive effects on fibronectin synthesis were observed with the small static load (0.016 MPa) inherent in the design of the chamber. PMID- 8356339 TI - Transient early metabolic and functional hyperreactivity and late areactivity of lymphocytes in preleukemic AKR mice. AB - The dynamics of changes in the metabolic and functional activities of thymus, lymph node and spleen lymphocytes and spleen macrophages of AKR mice was examined during the preleukemic period. The MTT colorimetric assay was used to determine the mitochondrial enzyme activity of viable cells, the local xenogeneic GVH reaction and the IL-2 assay for measuring T cell responses, and the IL-1 assay as an indicator of macrophage activity. In the early preleukemic period (at 1.5 months of age), lymphocyte dehydrogenase enzyme hyperactivity was accompanied by a highly increased production of IL-2, positive local xenogeneic GVH reaction and increased IL-1 production. Later on, at the age of 4-5 months, AKR mice demonstrated a progressive decrease in the metabolic activity of lymphocytes, negative local GVH reaction and reduction or lack in IL-2 and IL-1 production. This early hyperreactivity and late, gradually evolving, areactivity of lymphocytes and macrophages was not found in other, non-leukemic strains of mice (RFM, CBA, C57BL). PMID- 8356338 TI - Cell proliferation and prevalence of ras gene mutations in 7,12 dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. AB - Exposure of female inbred Sprague-Dawley Curl rats to intragastric 7,12 dimethylbenz(a)anthracene (DMBA) resulted in a variety of benign and malignant mammary tumors exhibiting a wide spectrum of proliferative activity as measured by [3H]-thymidine autoradiography. On the basis of earlier observations of 21% H ras codon 61 mutations in DMBA-induced rat mammary tumors reported by Zarbl et al., the prevalence of this type of ras gene mutation was studied in relation to the rate of proliferation in individual benign and malignant tumors. In a series of 50 mammary tumors exhibiting highly different proliferation activities we did not detect any H-ras codon 61 mutations after allele-specific dot blot hybridization of PCR-amplified material obtained from paraffin sections. Neither mode of proliferation nor type of differentiation appears related to H-ras codon 61 mutations. The relevance of activated ras genes for rat mammary carcinogenesis appears restricted to model systems using N-methyl-N-nitro-sourea (MNU) as initiating carcinogen. PMID- 8356340 TI - Recovery of pressor response to norepinephrine following relief of the obstructed common bile duct in the rat. AB - Jaundice caused by common bile duct (CBD) obstruction is associated with a blunted pressor response to norepinephrine (NE). We studied the rate and extent of recovery of the pressor response in the rat following relief of the obstruction. Three groups of male Wistar rats underwent CBD ligation. In the first and second group blood pressure measurements were obtained at 72 and 144 h after CBD ligation, respectively. In the third group pressure measurements were recorded 72 h after the relief of a 72-h obstruction. A fourth group served as control, and measurements were obtained 72 h after a sham operation. In all four groups measurements included basal blood pressure and pressure change following escalating doses of NE, ranging from 0.5 to 10 micrograms/kg. Basal blood pressure was similar in all four groups. In the control group the change of blood pressure was 23.4% +/- 6.7% in response to the lowest dose of NE, and 83.5% +/- 24.9% in response to the highest dose. A blunted pressor response to NE was recorded in all three groups with CBD obstruction. The duration of CBD ligation (72 or 144 h) did not affect this blunded response. Re-establishment of bile flow for 72 h made only a slight improvement in the response to NE. Obstruction of the CBD was associated with hyperbilirubinemia which disappeared following the re anastomosis of the CBD to the duodenum. This most significant decrease in serum bilirubin was not associated with a similar improvement in pressor response to NE. We conclude that in the rat CBD obstruction is associated with a blunted pressor response to NE, that relief of CBD obstruction for 72 h is insufficient to abolish this response, and that there is no full correlation between serum bilirubin and pressor response. PMID- 8356341 TI - Electromyographic evaluation of the gastrointestinal tract in dogs with short bowel syndrome. AB - Seven dogs were subjected to resection of 80% of the total length of the small bowel. Seven pairs of electrodes were implanted in the seromuscular layer of the antrum and remaining small bowel. Electromyographic recordings were obtained during fasting and after milk ingestion. Slow waves were identified in all sites studied and their frequencies were 4.7 +/- 0.4/min in the antrum; 17.5 +/- 0.58/min in D1; 17.5 +/- 0.61/min in D2; 17.43 +/- 0.65/min in J1; 17.40 +/- 0.62/min in J2; 10.28 +/- 0.77/min in I1; and 9.81 +/- 0.53/min in I2. The phase III of the migrating motor complex was identified in only one recording. Ingestion of milk caused the appearance of the fed pattern in all recording sites, except the antrum. It is concluded that extensive resection of the small bowel causes reduction of the slow wave frequency in the gut distal to the resection and disappearance of phase III of the migrating motor complex. PMID- 8356342 TI - Cardiovascular and catecholamine responses to acute haemorrhage in anaesthetized potassium-adapted rats. AB - The experiments were designed to determine whether potassium-loaded rats have a deficient recovery of blood pressure after a rapid arterial haemorrhage. Potassium loading was achieved by providing a 0.75% KCl solution as drinking fluid for 14 days, while control rats had either distilled water or tapwater. MAP, HR, Hct, and plasma electrolytes were determined before and after 1 and 2% body weight haemorrhage in anaesthetized Sprague-Dawley rats. Potassium-loaded rats had significantly reduced blood pressure recovery within 20 min after haemorrhage. HR was significantly reduced within 5 min only after 2% haemorrhage in potassium-adapted rats. Haemorrhage induced significant hyperkalaemia which was greater and significantly prolonged after 2% haemorrhage. The significant fall in Hct after haemorrhage was not affected by the magnitude of haemorrhage. In an additional group of rats, the pressor response to intravenous infusion of vasopressin was unaffected by potassium loading, whereas that to noradrenaline and angiotensin II was significantly reduced throughout the 20 min of infusion. The peak increase in blood pressure after phenylephrine injection was, however, unaffected by potassium loading. Basal plasma catecholamines concentration as well as concentrations after 1% haemorrhage were unaffected by potassium loading. It is concluded that the reduced vascular response to noradrenaline and angiotensin contributed to the reduced recovery of blood pressure after haemorrhage in potassium-loaded rats. Furthermore, the result with phenylephrine suggest a mechanism that is unrelated to direct vascular effects of noradrenaline and angiotensin II. PMID- 8356343 TI - Identification of viruses with bi- and trisegmented double-stranded RNA genome in faeces of children with gastroenteritis. AB - Polyacrylamide gel electrophoresis of nucleic acid extracted from faecal samples of diarrhoeic children revealed the presence of group A rotavirus in 50 (23.4%) samples and group C rotavirus in 1 (0.5%) sample out of 214 tested. One other sample showed the presence of three bands (with apparent length of 2.92, 2.37 and 1.32 kbp) which by enzymatic digestion analysis, were shown to consist of double stranded RNA (dsRNA). The sample was shown by electron microscopy to contain virus particles with a diameter of 32-34 nm. On the basis of morphology and genomic characteristics, this virus closely resembles a virus hitherto described only in chickens by Leite et al. in 1990 and tentatively named "picotrirnavirus". From the same group of 214, one sample containing a "picobirnavirus" was also identified. Thus, small icosahedral viruses with either a bior trisegmented dsRNA genome appear to infect humans. However, their pathogenic potential remains to be established. PMID- 8356345 TI - Detection of HIV1 DNA by a simple procedure of polymerase chain reaction, using "primer-dimer" formation as an internal control of amplification. PMID- 8356344 TI - Coronary artery lesions and human immunodeficiency virus infection. AB - The postmortem anatomopathological examination of eight heart-and-lung specimens obtained from eight HIV-seropositive patients was performed. Three patients were CDC stage II and five patients were CDC stage IV. The mean age was 27 (range: 23 32). Distal and proximal vascular lesions of the coronary arteries were observed. These impairments were marked by major excentric atherosclerosis (with 80-90% obstruction of the arterial lumen) or by fibrosis two-fold or six-fold the thickness of the tunica media. Sclero-hyalinosis of the smaller arteries and myocardial interstitial fibrosis lesions was also revealed. In view of the severity of the described lesions, the absence of any associated cardiovascular risk factors and the context of immunodepression, the role of a virus in the genesis of these lesions is suggested, in particular a virus of the herpes group. PMID- 8356346 TI - Neurocysticercosis. PMID- 8356347 TI - Echinococcosis affecting the central nervous system. PMID- 8356348 TI - Trichinosis of the central nervous system. PMID- 8356349 TI - Amebic brain abscess and meningoencephalis. AB - Infections caused by the free-living amebae remind us of the fine line that divides environmental and pathogenic microorganisms, and the number and complexity of the threats our natural defenses must cope with routinely. The comparative rarity of amebic brain infections, and their devastating consequences, demand utmost vigilance from the clinician. Although in many cases nothing can be done to save the lives of persons with these maladies, early diagnosis and prompt therapy can be effective in some cases. Much remains to be discovered about the pathogenesis, diagnosis, and effective therapy of amebic CNS infections. PMID- 8356350 TI - Eosinophilic meningitis. PMID- 8356351 TI - Disseminated strongyloidiasis. PMID- 8356352 TI - Visceral and ocular larva migrans. PMID- 8356353 TI - Cerebral malaria. PMID- 8356354 TI - Spinal and cerebral schistosomiasis. PMID- 8356355 TI - Cerebral paragonimiasis. PMID- 8356356 TI - Trypanosomiasis of the central nervous system. AB - American (Chagas' disease) and African (sleeping sickness) trypanosomiasis are diseases that are endemic in parts of Latin American and Africa, respectively. Physicians in developed countries may occasionally see cases because of extensive travel and immigration from endemic countries. In addition, in American trypanosomiasis, transmission via contaminated blood transfusions poses significant risks of causing acute Chagas' disease in immunocompromised patients. Both forms of trypanosomiasis have neurologic manifestations. Chagas' disease can present as acute meningoencephalitis in children and some immunocompromised patients. Additionally, there are increasingly frequent reports of neurologic syndromes, including CNS mass lesions, in HIV-infected patients. African sleeping sickness has prominent CNS pathologic features in stage II disease. Proposed pathogenetic mechanisms and diagnostic and therapeutic considerations are reviewed in this article. PMID- 8356357 TI - Serodiagnosis of parasitic infection of the central nervous system. PMID- 8356358 TI - Luther in worms and vice versa. PMID- 8356359 TI - Patient satisfaction and design of treatment. Results from a study of two different ways of treating hypertension. AB - OBJECTIVE: To compare patients' experiences of two different treatments of hypertension (non-pharmacological and pharmacological) and study to what extent seven specified factors of treatment differ between the two groups and the impact of these factors on patient satisfaction. DESIGN: Postal questionnaire with structured and open questions concerning the treatment. SETTING: Ten health centres in mid-Sweden. PARTICIPANTS: The 165 patients in the non-pharmacological group participated in a two-year-long study called Non-pharmacological treatment of hypertension (NPTH) at eight health centres. The 85 patients in the control group were recruited from two health centres providing traditional, pharmacological treatment of hypertension. MAIN OUTCOME MEASURE: Statistical comparisons between (the questionnaires from) the two groups. RESULTS: The results show that the patients in the NPTH-group considered that six out of seven factors had a more positive influence on them than the C-group. The six factors are doctor continuity, patient-doctor relation, patient participation, responsibility, control, and knowledge. The seventh factor is accessibility. CONCLUSIONS: The NPTH-group to a greater extent than the C-group had positive experience of all but one of seven factors of treatment studied. The factors studied are assumed to be an important part of patient satisfaction in outpatient health care. PMID- 8356360 TI - Patterns of abuse of the elderly in their own homes as reported by district nurses. AB - This study aimed at describing patterns of abuse of elderly persons living in their homes as experienced by district nurses in a county of Sweden. 12% of the district nurses (n = 153) reported 30 cases. Those abused were 78.7 years old (mean) and half of them had disturbed memory and mental state and were mostly isolated. The abuser was a relative of the abused person and 64.2 years old (mean). Psychological abuse was the most frequently reported kind of abuse. Along with the abuse the abusers' behaviour was commonly experienced as unpleasant and aggressive and/or combined with family conflicts. The results indicated that abuse is very much a family affair. To guide district nurses in a family-oriented approach is justified by the results. It also seems important further to investigate the pattern of how the different types of abuse occur. PMID- 8356361 TI - Dementia day care and its effects on symptoms and institutionalization--a controlled Swedish study. AB - OBJECTIVE: To examine the effects of Day Care (DC) on demented patients. DESIGN: A prospective non-randomized concurrent-control study. PARTICIPANTS: 55 demented patients in DC and 44 controls. SETTING: Sundsvall, an industrial community in northern Sweden. MAIN OUTCOME MEASURE: Cognition, ADL-functions, behaviour and institutionalization. RESULTS: Measurements of cognition, ADL-functions, and behaviour showed no or only small differences between the groups. After one year, 24% of the patients in the DC-group were institutionalized, compared with 44% of the controls. In the control group, the exhaustion of spouse and supervision need were highly correlated to institutionalization (p < 0.001), while high physical nursing load was correlated to institutionalization in the DC-group (p < 0.01). CONCLUSION: DC postpones institutionalization, probably because of less exhaustion of spouses and decreased supervision need. PMID- 8356362 TI - The Danish version of the Nottingham Health Profile: its adaptation and reliability. AB - OBJECTIVE: To test the reliability of the Danish version of the Nottingham Health Profile. DESIGN: Test-retest reliability with an interval of four weeks between administrations of the measure. SETTING: Copenhagen. PARTICIPANTS: Seventy patients suffering from osteoarthrosis, living at home and awaiting hip replacement operation. The patients' ages ranged from 37 to 90 years, with a median of 72 years. OUTCOME MEASURE: The Danish version of the Nottingham Health Profile, a measure of perceived health status, widely used in Europe. The measure consists of six sections; pain, physical mobility, energy level, sleep, social isolation, and emotional reactions. RESULTS: The respondents scored highly on the measure, particularly on the pain, physical mobility, and energy sections. No major differences in scores associated with age or sex were found. The test retest correlation coefficients obtained for the six sections were high (ranging from 0.76 to 0.86) and comparable with those found in Sweden and the UK. The test retest correlation for the whole measure was 0.93. CONCLUSION: The Danish version of the Nottingham Health Profile has been shown to be reliable and to be acceptable and relevant to patients with chronic disability. Should the formal tests of validity currently in progress prove satisfactory, Danish clinicians and researchers will have a valuable tool available for gaining insight into the impact of illness and its treatment on patients. PMID- 8356363 TI - Clinical assessment of pregnant women's psychosocial conditions, prematurity and birth weight. AB - OBJECTIVE: To seek a relation between pregnant women's psychosocial condition, assessed clinically in general practice, and prematurity and birth weight of the child. DESIGN: Clinical assessment early and late in pregnancy of psychosocial condition based on all accessible information, which included an extended history on psychosocial condition supplemented by background information about the woman and her social network and clinical observations. SETTING: Antenatal care in a general practice. RESULTS: The women assessed as having psychosocial difficulties were younger, had less education, and gained less weight in pregnancy. Birth weight was related to parity, body mass index before pregnancy, and total weight gain in pregnancy. A relationship was found between difficult psychosocial conditions and prematurity and low birth weight of the child. If the assessment of psychosocial condition had been based on the women's verbal descriptions of their problems alone, no relationship would have been found between psychosocial difficulties and prematurity and birth weight of the child. CONCLUSION: A clinical assessment of a woman's psychosocial condition, in which all accessible information is used, and an emphasis on emotional and social support for women when needed, may be necessary for improvement of antenatal care. PMID- 8356364 TI - The value of screening for retinopathy and microalbuminuria in patients with type 2 diabetes in primary health care. AB - Patients with type 2 diabetes (NIDDM) attending the Primary Care Centre in Molnlycke, Sweden, were evaluated regarding their metabolic status, microalbuminuria (UAER), and hypertension. An ophthalmological examination was performed, and two diagnostic methods, slit-lamp biomicroscopy and fundus photography, were compared. Nearly half the patients (42%) had diabetic retinopathy, mainly of the background type. Retinopathy was associated only with the duration of the disease, but the prevalence was as high as 20% within 0-4 years of the diagnosis. Fundus photography was easy to apply, except in the age groups above 80 years, in otherwise healthy and mentally cooperative patients. Fundus photography could not be applied in only 7% of the patients for ophthalmological reasons. The prevalence of microalbuminuria (20-200 micrograms/min) was high--34%--with another 8% above that range. Male sex, mode of antidiabetic treatment, and hypertension were associated with an increased UAER. Screening for retinopathy and microalbuminuria is valuable in primary health care in order to detect treatable diabetic retinopathy and to trace patients with microalbuminuria, a risk factor for clinically overt nephropathy as well as for cardiovascular diseases. PMID- 8356366 TI - Health service consumption and parent reported episodes of illness in children 0 3 years. AB - OBJECTIVE: To describe health service consumption and to find out whether a series of possible explanatory variables can help us to predict the number of contacts among children. DESIGN: A prospective study following a cohort of children during the first four years of life. SETTING: A municipality in southern Norway. PARTICIPANTS: 183 children born in the community from October 1979 to and including December 1980. MAIN OUTCOME MEASURE: Direct and indirect encounters with general practitioners (GPs) from the bills to the national insurance office, outpatient encounters and hospital admissions from the hospital files, and episodes of illness as reported in postal questionnaires to the parents. RESULTS: Each child had on average 10.6 GP contacts (2.6 per year), and the frequency of contacts decreased as they grew. Telephone contacts were almost as frequent as consultations at the doctor's surgery, and the doctors made more home visits to the youngest children. Of the contacts, 4/5 took place in the day time, but most of the home visits took place during the evening/night/weekend. Each child had 1.9 hospital contacts in 4 years, i.e. 0.3 admissions and 1.6 outpatient department contacts. The parents reported an average of 11.5 episodes of illness during the period, more than twice as many in the first year as in the last year. Information about sex, duration of breast feeding, smoking in the family, family history of allergy, parents' education, whether in kindergarten, and presence of psychosocial problems cannot help in predicting health care consumption. CONCLUSION: The low number of contacts with GPs can partly be explained by the fact that the children also have contact with a well-baby clinic. In our study, a series of possible explanatory factors did not help us to predict the amount of health care consumption during the first four years of life. PMID- 8356365 TI - Myocardial infarction risk factors and well-being among 50-year-old women before and after the menopause. The population study "50-year-old people in Kungsor". AB - OBJECTIVE: To examine whether early menopause has a negative influence on the traditional ischaemic heart disease (IHD) risk factor pattern and on well-being. DESIGN: Cross-sectional population study. SETTING: Kungsor, a semirural community in mid-Sweden. PARTICIPANTS: All 155 women in Kungsor who became 50 years old in 1984-7. MAIN OUTCOME MEASURES: Traditional IHD risk factors and self assessed well-being measures. RESULTS: Women who smoked had an earlier menopause than others. Postmenopausal women had significantly higher serum cholesterol levels (and haemoglobin levels), and more sleep disturbances than premenopausal women. There were no significant differences in other self-rated well-being, but home and family situation, patience, anxiety, and sleep disturbances tended to become worse with time from menopause. CONCLUSIONS: These findings may be interpreted as evidence indicating that the menopause affects the IHD risk factor profile and well-being negatively. PMID- 8356367 TI - Alcohol-use patterns in young university students in Finland. AB - OBJECTIVE: To obtain descriptive data on the alcohol-use patterns and the factors affecting them among Finnish first-year university students. DESIGN: Cross sectional survey with a self-administered questionnaire. SETTING: Finnish first year university students. PARTICIPANTS: 3,836 students during the academic year 1989/90. The participation rate was 73.7% for female and 53.6% for male students. MAIN OUTCOME MEASURE: Frequency of drinking alcohol, heavy drinking, and drinking for intoxication, average alcohol consumption. RESULTS: The mean alcohol consumption for female students was 2.6 kg and for male students 6.5 kg of pure alcohol per year. 6.5% of the female students and 5.1 of the male students were abstainers. The heaviest drinking 10% consumed 42% of all consumed alcohol. 4.9% of the female students reported a consumption of at least 10 kg of pure alcohol per year and 11.7% of male students reported a consumption of at least 15 kg. The median for the frequency of drinking was every second week for the females and once a week for the males. Furthermore, drinking for intoxication was more frequent among the male than the female students. CONCLUSION: Male students have a higher alcohol consumption, drink more frequently, and are more often intoxicated than female students. PMID- 8356368 TI - Characteristics of young female smokers in a Swedish primary health care area. AB - OBJECTIVE: To analyse the correlation between smoking, socioeconomic characteristics, and sexual and contraceptive patterns in young women. DESIGN: Cross-sectional population study, smokers compared with non-smokers. SETTING: Nattraby-Hasslo, a rural area in southern Sweden. PARTICIPANTS: All women between 15-34 years of age (n = 541). RESULTS: 26% smoked daily. Smokers on average had less schooling, lower 9th grade results, less satisfaction in school, and more unskilled professions than non-smokers. Apart from a higher parental divorce rate among smokers, no correlation between parental factors and smoking was found. Smokers on average reported an earlier sexual debut, more unprotected first intercourse, more life-time sexual partners, and more legal abortions. CONCLUSION: Smoking is associated with sexual habits, which may reflect a higher tendency to take personal risks among smokers. PMID- 8356369 TI - Medical theories derived from clinical practice. PMID- 8356370 TI - Manual therapy with steroid injections in low-back pain. Improvement of quality of life in a controlled trial with four months' follow-up. AB - OBJECTIVE: To compare prospectively the effect of manual treatment such as manipulation, specific mobilization, muscle stretching, auto-traction, and cortisone injections with standardized conventional but optimized activating treatment by primary health care teams. DESIGN: Prospective controlled multicentre trial with four months' follow-up. SETTING: Kopparberg County, Sweden. Six primary health care or occupational health care centres, representing a catchment area of 56000 residents participated. PARTICIPANTS: 101 outpatients with acute or subacute low-back pain were, during the period February 1988 to April 1989, randomly allocated to one of two treatment groups. MAIN OUTCOME MEASURE: Quality of life was assessed at baseline and at four months by means of visual analogue scales (VAS). The occurrence of 27 different symptoms of a psychosomatic character was surveyed initially and at four months by questions answered by "yes" or "no" in a questionnaire. RESULTS: There were significant differences concerning quality of life and presence of general symptoms in favour of the group receiving manual treatment with steroid injections. CONCLUSION: Manual treatment with steroid injections was superior to conventional treatment in minimizing mental and somatic symptoms and increasing quality of life, in parallel with other measures of improvement. PMID- 8356372 TI - Patients' perceptions--a shift in medical perspective. AB - Based on an empirical study in general practice, patients' perceptions and a fundamental shift in medical perspective are described. The research material was collected in a prospective interview-study that included 13 general practitioners and 35 patients (24 female and 11 male). Patients and doctors were interviewed before and after the consultation. A semistructured schedule was followed, and all 175 interviews were performed by the investigator, and taped. A patient perception-model of health, based on the analysis of the interviewdata, became the framework for describing the complexities of illness experiences. The coupling of viewpoints revealed that patients and doctors live in different conceptual worlds. Often they did not know the extent to which their perceptions were different, nor why. The aspects of disease that lie outside the biomedical field have not hitherto been of great interest in medical research. However, our ability to act on the humanistic dimensions in everyday clinical settings depends on knowledge about these as well. Medical human science research may give us new conceptions and theories in this complex territory. PMID- 8356371 TI - Ketoprofen controlled release (CR) in the treatment of osteoarthrosis; a double blind, randomized multicentre study of single morning versus evening dose. Norwegian Study Group of General Practitioners. AB - OBJECTIVE: To compare the morning and evening dose of 200 mg ketoprofen controlled release formulation with regard to both efficacy and GI tolerability. DESIGN: Double-blind, randomized multicentre prospective trial with cross-over design combined with a parallel design. PARTICIPANTS: One hundred and eight female and 55 male patients with osteoarthrosis in hip(s) or knee(s) necessitating treatment with nonsteroidal antiinflammatory drugs. MAIN OUTCOME MEASURE: The degrees of pain and stiffness and joint movement ability in joints with osteoarthrosis. RESULTS: Both the morning and the evening dose demonstrated a significant effect (p < 0.01) on all efficacy variables. The reduction in degree of pain in the afternoon and in the evening was significantly higher (p < 0.01) for the morning dose. The total frequency and degree of gastrointestinal discomfort increased significantly (p < 0.01) during both treatment periods. The increases were mainly caused by increased gastric pain and constipation. No significant differences were found between the two regimes regarding tolerability. CONCLUSION: Ketoprofen controlled release given once daily in the morning compared to the evening to patients with osteoarthrosis may increase the efficacy without reducing the tolerability of the drug. PMID- 8356373 TI - 'Sports anaemia'. Does it exist? PMID- 8356374 TI - Exercise-induced hypoxaemia in elite endurance athletes. Incidence, causes and impact on VO2max. AB - Arterial oxygenation is well maintained in healthy untrained or moderately trained individuals during exercise. In contrast, approximately 40 to 50% of healthy elite endurance athletes (cyclists and runners) demonstrate a significant reduction in arterial oxygenation during exercise at work rates approaching VO2max. The mechanism(s) to explain this exercise-induced hypoxaemia (EIH) remain controversial. However, hypoventilation and venoarterial shunt do not appear to be involved. By elimination, this suggests that ventilation-perfusion inequality and/or pulmonary diffusion limitations must contribute to EIH in this population. Theoretical and direct experimental evidence exists to support the notion that both ventilation-perfusion inequality and diffusion disequilibrium contribute to EIH; however, the relative contribution of each factor remains to be determined. In athletes who exhibit a profound EIH, the exercise-induced decline in arterial oxygenation results in a limitation of VO2max. Further, athletes who exhibit EIH at sea level suffer more severe gas exchange impairments during short term exposure to altitude than athletes or nonathletes who do not exhibit EIH at sea level. This finding explains much of the observed variance in the decline in VO2max among individuals during short term altitude or hypoxia exposure. PMID- 8356375 TI - Physical fitness and adults with mental retardation. An overview of current research and future directions. AB - The deinstitutionalization movement of the past 25 years has focused on the placement of people with mental retardation into community-based settings. There is a need for exercise- and health-related professionals to demonstrate a thorough understanding of the term mental retardation and all of the intellectual and behavioural ramifications that coexist with this condition before addressing the 'how to' of fitness evaluation. Therefore, the article outlines the range of intellectual and behavioural characteristics of this population, based on the level of retardation. Many researchers investigating body composition have reported that a disproportionate number of adults with mental retardation carry a percentage of body fat that would be considered unhealthy (e.g. it increases the risk of early onset of such diseases as hypertension and adult onset diabetes mellitus). Living arrangements (i.e. institution vs smaller residences) play a role in the prevalence of obesity. Many attempts of researchers to control weight in adults with mental retardation through caloric restriction, exercise, and a combination of diet and exercise, have had a varied outcome. Cardiovascular capacity is considered by most exercise physiologists as the major physiological indicator for overall fitness. The majority of researchers who have evaluated the cardiovascular fitness levels of adults with mental retardation have reported fitness levels representative of a very sedentary population. Therefore, one would expect a keen sense of urgency among researchers to develop training regimens targeted specifically for people with mental retardation. Many have been developed, but to date only 2 cardiovascular training regimens have been reported that specifically describe the necessary components of an exercise programme (i.e. frequency, duration, intensity) that would allow for reproducibility--a stationary bicycle routine using the Schwinn 'Air-Dyne' ergometer and a run/walk programme. Of these, only the programme using the Schwinn 'Air-Dyne' ergometer reported significant improvements in cardiopulmonary fitness. Researchers have demonstrated that: (1) body strength is valuable for recreation activities and activities of daily living; (2) competence in upper body muscular skills is a prerequisite for many available vocational opportunities; and (3) positive correlations have been established between muscular strength and industrial work performance in people with mental retardation. Therefore, there is a need for appropriate evaluation procedures for determining the muscular strength and endurance of people with mental retardation. The future directions for researchers and professionals concerned with the fitness status of people with mental retardation includes answering question such as: What will be the effect of obesity on general health status?(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8356377 TI - Weight-training injuries. Common injuries and preventative methods. AB - The use of weights is an increasingly popular conditioning technique, competitive sport and recreational activity among children, adolescents and young adults. Weight-training can cause significant musculoskeletal injuries such as fractures, dislocations, spondylolysis, spondylolisthesis, intervertebral disk herniation, and meniscal injuries of the knee. Although injuries can occur during the use of weight machines, most apparently happen during the aggressive use of free weights. Prepubescent and older athletes who are well trained and supervised appear to have low injury rates in strength training programmes. Good coaching and proper weightlifting techniques and other injury prevention methods are likely to minimise the number of musculoskeletal problems caused by weight training. PMID- 8356376 TI - Blood lactate measurement in recovery as an adjunct to training. Practical considerations. PMID- 8356378 TI - Golfing injuries. An overview. AB - Golf is becoming an increasingly available and popular sport. It is played by people of all ages and abilities, which accounts for a wide spectrum of injury. Few reports of injuries exist, but increasing media attention of the golfing injuries of professional players has raised the profile of these medical conditions. Numerically, the vast majority of problems occur from soft tissue musculoskeletal injuries rising principally from overuse. The injury pattern seen is influenced by the age, ability and amount of play. Anatomically, most injuries are localised to the back, wrist, elbow and shoulder. In addition to causing new injuries the game may cause recrudescence of old injuries and exacerbate pre existing degenerative disease. A different injury pattern is seen among elite players compared with recreational players, and this relates to skill and amount of practice. Appropriate conditioning and attention to technique may help to reduce the incidence of injury. There are no injuries exclusive to golf, however fracture of the hamate bone is an uncommon injury seen in sports involving the use of a club or bat. The high number of childhood golf-related head injuries is disturbing. Most of these arise from blows to the head from a golf club and highlight the need for early tuition in the safety aspects of the game. PMID- 8356379 TI - Will multimodality therapy solve the enigma of long-term survival for squamous cell carcinoma of the esophagus? AB - Squamous carcinoma of the esophagus is a disease with a poor prognosis which fortunately occurs seldom in the United States. Because patients present with more advanced disease here, surgical therapy has not equaled results reported from Asia. Although, claims of equality have appeared in the literature, radiation therapy alone has not been very effective for this disease. There are a myriad of small reports which extol a variety of combined approaches. Based upon a review of these series it is obvious that a Phase III trial is required to establish the best multimodality therapy for management of squamous carcinoma of the esophagus. Components of such a trial are reviewed and suggestions are made for design and reporting of such a trial. PMID- 8356380 TI - Efficacy of multimodality therapy in gastric adenocarcinoma. AB - Multimodality therapy has not reproducibly improved the survival of patients with gastric adenocarcinoma. This is largely because the staging of disease has been imprecise and because the current regimens have only limited efficacy against advanced disease. Until staging is improved and active regimens are found, it will be difficult to identify synergism between surgery and other treatment modalities. PMID- 8356381 TI - Influence of multimodality therapy on the management of pancreas carcinoma. AB - Carcinoma of the pancreas has an especially grim prognosis. Only 1-3% of patients survive for 5 years. Radical pancreaticoduodenectomy, especially for minimal disease, is currently the only chance for cure. While radiation therapy does not improve overall survival, it may improve local control following radical resection and decrease pain in locally advanced cancers. Although chemotherapy has led to significant improvements in survival in patients with locally advanced disease, the overall effect is small. When surgery, radiotherapy, and chemotherapy are administered to localized carcinomas in randomized, prospective trials, survival is significantly lengthened. Similar trials in locally advanced, unresectable pancreatic cancer also confirm the concept of synergistic interaction between therapies. Thus, pancreas carcinoma is one neoplasm where multimodality therapy has had a demonstrable, although small effect. PMID- 8356382 TI - Evolving role of surgery after induction chemotherapy and primary site radiation in head and neck cancer. AB - Chemotherapy, as preliminary treatment before surgery and/or radiation for advanced squamous cell carcinoma of the head and neck, is no longer novel. In prospective trials to date, however, multiple agent induction chemotherapy has yet to demonstrate the initial presumptive promise of improved rates of cure. As an alternate goal, there has emerged a renewed attentiveness toward limiting treatment morbidity, several strategies for which may be considered. Extirpative, often radical, surgery on the primary site of disease usually represents the most significant threat to life quality. Various ways of limiting surgical morbidity will be considered by way of introduction. The trends of head and neck cancer treatment over the decades, leading into the era of induction chemotherapy and refined radiation techniques, will be described. At the combined Dana-Farber/New England Deaconess Head and Neck Oncology Clinic, an experience with over 300 patients receiving induction chemotherapy for advanced head and neck cancer has been analyzed with an emphasis on the postulate of lessening the extent of surgery in appropriately selected patients. In a comparison between trials initiated in 1980 and 1987, improved complete response rates from 26 to 57% were documented. Survival rates were identical, but the use of planned primary site ablative surgery was decreased from 47 to 14%. While some increase in local failure has been noted in patients treated by primary site radiation alone, surgical salvage appeared to be more effective. The implication of these trends for patterns of failure and surgical salvage and data concerning the need for neck dissection in this group of patients will be briefly summarized. Other trials addressing organ-preservation strategies will also be referenced and the dichotomy between survival-based studies and morbidity-limiting studies illustrated. Independent trends in radiation technique as a potential substitute for traditional surgical practice will be reviewed. PMID- 8356383 TI - Impact of combined modality therapy on the treatment of adenocarcinoma of the colon. AB - An emphasis on careful surgical staging of adenocarcinoma of the colon has improved the predictive value of tumor staging systems. As a result of improved staging and carefully conducted randomized clinical trials, adjuvant therapy of locally advanced colon cancer, based on 5-fluorouracil chemotherapy, has been proven to substantially reduce recurrence rates and significantly increase overall survival for selected patients. Improved treatments and schedules are currently being studied in randomized trials and may increase the efficacy of this adjuvant therapy. Radiation therapy has not as yet been integrated into the adjuvant treatment of colon carcinoma. The application of a combined approach of surgery and chemotherapy in selected patients with liver metastases may also improve cure rates and long-term survival. The developing understanding of molecular determinants for the biological behavior of these cancers will increase the opportunities to identify, on the one hand, those patients who will benefit from specific therapies, and, on the other hand, new therapeutic strategies and treatments. PMID- 8356384 TI - Conservative management of rectal carcinoma: the efficacy of a multimodality approach. AB - The goals of the conservative management of adenocarcinoma of the distal rectum are to preserve rectal sphincter function and achieve excellent local tumor control. Multimodality therapy for more advanced disease suggests that these goals will be met by conservative surgery combined with radiation therapy and chemotherapy. Over 100 patients with T0-3 N0-1 lesions have been treated in prospective single institution trials with either local excision or anterior resection with coloanal anastomosis, usually combined with chemotherapy and radiotherapy. The typical criteria for local excision have been for lesions to be 4.0 cm or less, mobile, and not poorly differentiated or mucinous. Patients with larger or more advanced lesions may undergo anterior resection with coloanal anastomosis. Following resection, radiotherapy is delivered to the pelvis and tumor bed often with concomitant chemotherapy. The overall rate of local failure in the trials in which local excision is performed with postoperative chemoradiotherapy is 3% for T1 lesions, 5% for T2 lesions, and 30% for T3 lesions with a median follow-up of at least 25 months. Local failure in patients with a coloanal anastomosis is 9% overall. Salvage was successful in about half of the patients who failed locally. Importantly, nearly all patients remained continent. These institutional studies show that sphincter preservation can be used in patients who are objectively selected for this procedure. However, before this multimodality approach may be considered standard therapy the rate of local control must be confirmed in a large, Phase II, multicenter, prospective trial such as that now underway in many of the cooperative groups. PMID- 8356385 TI - Effect of combined modality therapy on the surgical management of locally advanced rectal carcinoma. AB - The treatment of locally advanced rectal carcinoma is one of the more complicated problems in the management of colorectal carcinoma. More than any other site successful treatment requires a multimodality approach as surgery alone is frequently insufficient to completely eradicate all disease. This review focuses primarily on the management of patients who present without prior treatment and discusses the role of preoperative radiation therapy as well as intraoperative radiation therapy. Although much less gratifying, patients who present after failing previous therapy may also benefit from an aggressive multimodality approach. PMID- 8356386 TI - Laparoscopy/thoracoscopy for staging: I. Staging endoscopy in surgical oncology. AB - The application of laparoscopy to the staging of solid abdominal tumors is reviewed. The current evidence support the use of laparoscopy particularly in hepatic tumors. There is evidence that the hospital length of stay for a patient with a nonresectable hepatic tumor can be reduced from 5.6 +/- 0.4 days with a laparotomy to 1.5 +/- 0.3 days with a laparoscopy. Where the palliative and bypass issues are not limiting, cases of pancreatic and gastric carcinoma also appear to benefit in having a staging laparoscopy before a formal laparotomy for resection. Current instrumentation does produce limits, but with future prospects of laparoscopic ultrasound, and tumor staining, staging laparoscopy will become an important diagnostic tool in surgical oncology. PMID- 8356387 TI - Laparoscopy/thoracoscopy for staging: II. Pretherapy nodal evaluation in carcinoma of the esophagus. AB - Many surgical studies show a significant stratification of survival following resection of esophageal cancer based upon accurate pathologic staging. However, investigators are moving away from single modality therapy toward multimodality trials for the treatment of this disease. This presents a problem in staging of patients before therapy is begun. Chemotherapy and/or radiation therapy may alter the local tumor characteristics and nodal metastases, thus confounding evaluation of treatment results. Although CT scanning and transesophageal ultrasound help in assessing nodal status, they have not reached the precision necessary for study purposes. Pretherapy nodal staging using video-assisted exploration may provide the same level of accuracy as mediastinoscopy does for lung cancer. PMID- 8356388 TI - Laparoscopic surgery for colon and rectal cancer. AB - Laparoscopic techniques are now being applied to increasing numbers of general surgical procedures. Technical feasibility, margins, number of lymph nodes, and recurrence rates need to be assessed with the application of this new technique to colon or rectal malignancies. Technically, the right colon, sigmoid, and proximal rectum appear to be the most amenable to laparoscopic assisted or complete laparoscopic resection. Early results from a registry of laparoscopic assisted colectomies shows that there is no significant difference in the number of lymph nodes in the lymphovascular bundle compared to conventional colon resections. Early retrospective reports indicate that there may be a significant decrease in post op length of stay. We conclude that the technique of laparoscopic assisted colectomy for colon or rectal cancer needs to follow the same oncologic principles as that of conventional surgery, and ultimately a trial will be needed to compare conventional and laparoscopic cancer resections of the large bowel. PMID- 8356389 TI - Relevance of quality of life assessment to the evaluation of combined-modality therapy. AB - Quality of life (QOL) assessment is a research tool which is incorporated into clinical trials to provide information about the ways in which the treatment affects the individuals sense of well-being and his physical, psychologic, and social functions. In the appropriate setting QOL assessment offers additional endpoints, beyond the traditional response rates and survival durations, to evaluate cancer treatments in ways which can be particularly meaningful to patients. Selected aspects of QOL methodology and the application of QOL assessment to the evaluation of combined-modality therapies for gastrointestinal cancers are discussed. PMID- 8356390 TI - Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. AB - Interleukin-6 (IL-6) was detected at low levels in plasma [0.014 +/- 0.006 ng/ml (mean +/- SEM] and in high amounts in synovial fluid [SF; 2.6 +/- 2.2 ng/ml (mean +/- SEM)] of patients with rheumatoid arthritis. No correlation of IL-6 levels in plasma or SF with the ESR (n = 15) or with histological parameters of acute local synovitis (n = 10) was observed. In contrast, SF IL-6 was positively correlated with histological characteristics of chronic synovitis (n = 10; P < or = 0.01) and elevated plasma IgG concentrations (n = 15; P < or = 0.05). In vitro concentrations of IL-6 comparable to those detected in SF increased the production of both IgG and IgM by synovial membrane mononuclear cells. The present results contribute to the view that high local IL-6 concentrations in SF promote chronic synovitis in RA. PMID- 8356391 TI - Differential expression of gelatinase B (MMP-9) and stromelysin-1 (MMP-3) by rheumatoid synovial cells in vitro and in vivo. AB - Primary cultures of adherent rheumatoid synovial cells (ASC) are comprised of variable proportions of fibroblasts, macrophages and stellate cells (activated fibroblasts). These cultures were shown to produce the metalloproteinases stromelysin-1 (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9) by Western blotting and zymography techniques. Immunolocalisation studies showed that MMP-3 was mainly produced by the fibroblastic cells whereas MMP-9 was restricted to macrophages (CD68 positive). Subcultured synovial fibroblasts, devoid of macrophages, did not produce MMP-9 as judged by zymography and immunolocalisation; but when stimulated with phorbol myristate acetate and interleukin-1 alpha both MMP-9 and MMP-3 were co-expressed. These 'activated' fibroblasts assumed a dendritic or stellate morphology, which in localisation studies was usually associated with enhanced enzyme production. Immunolocalisation studies of rheumatoid synovial tissue showed that relatively few cells were positive for MMP-3 and MMP-9. Localisation of MMP-9 corresponded to a proportion of macrophages positive for the CD68 marker throughout the synovial tissue. MMP-3 localisation was not associated with the macrophage marker, but was observed in both the synovial lining layer and deeper stromal locations. Widespread distribution of both enzymes was not observed in fresh tissues, but this increased in tissues subjected to short-term explant cultures. Thus, both in vitro and in vivo studies indicated that synovial fibroblasts or B cells are effective producers of MMP-3 whereas macrophages elaborate MMP-9, observations that demonstrated different metalloproteinase phenotypes under similar environmental conditions. PMID- 8356392 TI - Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing. AB - HLA-DR gene frequencies in 59 Japanese children with juvenile rheumatoid arthritis (JRA) and 62 Japanese adults with rheumatoid arthritis (RA) were analyzed by oligonucleotide DNA typing. As in other studies, the frequency of DRB1*0405 in RA patients was significantly higher than in the Japanese controls. In a comparison of non-classified JRA patients with Japanese controls, no significant differences were observed in the frequency of DR types. However, when the JRA patients were classified into four clinical types, i.e., a rheumatoid factor-positive [RF(+)] polyarticular type, a rheumatoid factor-negative [RF(-)] polyarticular type, a pauciarticular type, and a systemic onset type, DRB1*0405 was found to be significantly higher in the RF(+) polyarticular JRA patients than in the controls (P < 0.05). Thus, the RF(+) polyarticular type of JRA had the same HLA association as RA. This result is consistent with the fact that both RF(+) polyarticular JRA and RA cases have a similar clinical course. PMID- 8356393 TI - Toxicity of complement for chondrocytes. A possible source of cartilage degradation in inflammatory arthritis. AB - Cartilage from patients with rheumatoid arthritis and from animals with antigen induced arthritis is frequently contaminated with complement-containing immune complexes. A possible role for complement activation in cartilage degradation was modeled in vitro by exposing cultured bovine chondrocytes to homologous serum, and determining cytotoxicity by monitoring the release of intracellular 51Cr. Complement activation was found to be cytotoxic, having maximal effect at 20-30% serum by 18 h. Serum toxicity was ablated by heat (50 degrees C, 20 min) or methylamine treatment but not by EGTA, suggesting that in these experiments activation occurred by the alternate route. The implications of the results are discussed in relation to ultrastructural evidence for the involvement of complement in the pathogenesis of cartilage degradation in inflammatory arthritis. PMID- 8356395 TI - The T-cell antigen receptor enters its second decade. PMID- 8356394 TI - Detection of tumour necrosis factor alpha and interleukin-1 beta in the rheumatoid osteoarthritic cartilage-pannus junction by immunohistochemical methods. AB - During inflammation the rheumatoid synovial membrane is invaded by a number of different cell types. When activated most of these cells produce cytokines including tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta). These cytokines are believed to stimulate production of degradative enzymes and disturb the equilibrium between such enzymes and their inhibitors resulting in tissue damage. In this study we investigated the localisation of TNF alpha and IL-1 beta at the cartilage-pannus junction (CPJ). Here, cytokines are well placed to influence the integrity of articular cartilage. Tissue was derived from advanced rheumatoid (RA) and, as a comparison, osteoarthritic (OA) joints at the time of replacement surgery (arthroplasty). Antibody staining of fixed serial sections of tissue localised cells that were associated with IL-1 beta and TNF alpha. Cell markers for macrophages and endothelial cells were included to provide positive identification of the cytokine-associated cells. Analysis of these sections revealed that both TNF alpha and IL-1 beta were associated with macrophages, particularly those in the synovium overlying cartilage (pannus) and endothelial cells. Positive staining was seen at the CPJ in RA and in similarly located tissue in OA. The similar distribution of cytokines in OA was unexpected even if the overall numbers of tissue and infiltrating cells in the CPJ were different in the two diseases. This highlights the possible role played by endogenous inhibitors [1, 2] in influencing the degree of cytokine activity necessary to explain the different pathogenic mechanisms in RA and OA. PMID- 8356396 TI - A rapid method for selecting specific hybridoma clones using paramagnetic Dynabeads. AB - This paper describes how specific hybridoma clones can be rapidly selected using paramagnetic beads coated with the antigen used for immunization. Spleen cells from a mouse immunized with fragment D dimer (DD) from plasminolysed fibrin were first fused with X-63 mouse myeloma cells. Paramagnetic monodisperse beads (precoated with sheep anti-mouse antibodies) were then coated with S4, a monoclonal antibody to DD, and subsequently with DD. Mixing such beads with the fused cells allowed selective harvesting of cells with membrane-expressed anti-DD gammaglobulins using a magnetic particle concentrator. Within 24 h, the cells spontaneously detached from the beads and were plated out on 96-well plates. Supernatants from the clones obtained were tested by the ELISA technique. Antibodies specific for DD were produced by 40-79% of the tested clones. It is concluded that it is possible to use antigen-coated paramagnetic beads to select, prior to cloning, hybridomas that produce specific antibodies. Implementation of this technique has significantly reduced costs and time in our efforts to obtain hybridoma clones of interest. PMID- 8356397 TI - T-cell responsiveness to LCMV segregates as a single locus in crosses between BALB/cA and C.B-17 mice. Evidence for regulation by a gene outside the Igh region. AB - The course of systemic infection with lymphocytic choriomeningitis virus (LCMV) was studied in BALB/cA and C.B-17 mouse strains differing in the immunoglobulin heavy chain region (Igh). Susceptibility to intracerebral infection and the ability to clear the virus differed significantly between these presumably congenic strains, suggesting that a gene in the Igh region might influence the course of this infection. A difference in virus spread prior to appearance of the immune response could not explain the observed differences. On the other hand, the differences in course of infection correlated with a difference in virus specific T-cell responsiveness measured in terms of virus-specific cytotoxicity in vitro and delayed-type hypersensitivity in vivo. Analysis of F1, BC1 and F2 progeny showed that differential T-cell responsiveness was influenced by a single gene or gene complex; however, no linkage was found between this locus and the Igh-C region. Taken together, these results indicate that an additional, and previously unknown, genetic difference exists between these two mouse strains, and that the involved locus carries a gene which significantly affects T-cell responsiveness to LCMV. PMID- 8356398 TI - Preferential damage to IgM production by ultraviolet B in the cells of patients with Bloom's syndrome. AB - In most patients with Bloom's syndrome (BS), selective IgM deficiency is commonly found. We examined proliferative responses by incorporation of [3H]-thymidine and the production of immunoglobulin after ultraviolet B (UVB) irradiation in the cells of two patients with BS. With regard to the proliferative responses in peripheral blood mononuclear cells (PBMC) cultured with pokeweed mitogen (PWM), the patients' PBMC were more sensitive to UVB irradiation than controls. Although the effect of UVB irradiation in lymphoblastoid cell lines (LCL) after 0 days of culture showed no difference between one patient and controls, the patient's LCL were more sensitive to UVB than the controls after 3 and 7 days of culture. These results suggest that the proliferative responses of the patient's LCL recovered later than those of controls. IgM production was the most sensitive to UVB in the patients' PBMC and LCL. IgG and IgA production in the patients' PBMC and LCL showed the same sensitivity as controls. From our results, it is suspected that the preferential damage to IgM production by UVB is connected with the selective IgM deficiency of BS. PMID- 8356399 TI - Effects of growth factors on cytokine production in serum-free cultures of human thymic epithelial cells. AB - Human thymic epithelial cells (TEC) of medullary phenotype were cultured for 14 days in a growth factor-defined serum-free medium. The effects of added growth factors on cell numbers and the production of cytokines were investigated by separate exclusion of the various growth factors from the medium. We found that hydrocortisone stimulated cell proliferation but inhibited the differentiation of TEC and significantly reduced the production of interleukin-1 alpha, interleukin 6 and granulocyte-macrophage colony stimulating factor. Insulin was found to enhance the differentiation of TEC and the production of the three cytokines. Transferrin and choleratoxin were found to inhibit cell proliferation, but they did not affect production of the cytokines. Exclusion of epidermal growth factor, however, leads to cell death. We conclude that it is essential to exclude hydrocortisone from the medium to optimize production of cytokines, and that transferrin and choleratoxin seem to be unnecessary constituents in serum-free cultures of human TEC. PMID- 8356400 TI - Specific activation of human peripheral blood gamma/delta + lymphocytes by sonicated antigens of Mycobacterium tuberculosis: role in vitro in killing human bladder carcinoma cell lines. AB - Tumour regression induced in cancer patients by local instillation of Bacillus Calmette-Guerin (BCG) into the bladder has been considered to be mainly mediated by activated cellular immunity and inflammatory reactions. In the present study we investigated the cytotoxicity of T cells bearing gamma/delta T-cell receptors (gamma/delta + cells) against bladder carcinoma cells in vitro. Long-term cultured gamma/delta + T-cell lines from peripheral blood lymphocytes of healthy donors were established by stimulation with sonicated cell wall-associated antigens of Mycobacterium tuberculosis (SMA). These gamma/delta + T cells lack the natural killer (NK) markers CD16 and CD56, as determined by flow cytometry. The SMA-specific gamma/delta + T cells exhibited profound cytotoxicity against two NK-resistant bladder tumour cell lines as well as against NK-sensitive tumour cells in a non-major histocompatibility complex-restricted manner. The pattern of tumour cells killed by gamma/delta + T cells differed significantly from those of NK cells and lymphokine-activated killer LAK cells. Furthermore, we tested the effects of recombinant human cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF), on gamma/delta + T cell-mediated cytotoxicity. It was shown that the addition of recombinant TNF in co-incubation could augment gamma/delta + T-cell-mediated killing of two bladder tumour cell lines, but not of cells of the erythroleukaemia cell line K562. Based on these results it was concluded that mycobacterial antigens could specifically activate resting gamma/delta + T cells. The cytotoxicity of gamma/delta + T cells against bladder tumour cells and its selective enhancement by TNF may be an important mechanism involved in bladder tumour regression induced by intravesical instillation of BCG. PMID- 8356401 TI - Phenotypic and molecular characterization of human monoclonal TCR gamma/delta T cell lines from jejunum and colon of healthy individuals. AB - We have performed a phenotypic and molecular analysis of monoclonal TCR gamma/delta T-cell lines derived from jejunal and colonic biopsies of healthy individuals. Flow cytometric analysis employing a panel of 24 monoclonal antibodies (MoAbs) demonstrated that intestinal TCR gamma/delta intraepithelial lymphocytes (IEL) constitute a phenotypically heterogeneous population. Nucleotide sequence analysis of expressed TCR delta variable (V) regions revealed the dominant utilization of the V delta 2 and D delta 3 gene segments and frequent rearrangement of J delta 3. IEL V delta regions displayed extensive junctional diversity as a result of N and P insertion and the utilization of D delta 3 in all three reading frames. The results demonstrate that intestinal TCR gamma/delta T cells from healthy individuals constitute a phenotypically heterogeneous population expressing V delta regions that differ from their systemic counterparts. PMID- 8356402 TI - Expression of human IL-2 receptor alpha- and beta-chains using the baculovirus expression system. AB - The genes encoding the alpha- and beta-chains of the human interleukin-2 receptor were expressed in lepidopteran insect cells using the baculovirus expression vector system. The corresponding genes were inserted under the polyhedrin promoter of the Autographa california nuclear polyhedrosis virus and expressed in the Spodoptera frugiperda insect cell line during viral infection. The recombinant receptor proteins were identified in the insect cell lysates by using protein dot blot and ELISA techniques. At 36 h post infection the corresponding proteins were clearly detected using anti-IL-2 alpha- and beta-receptor-specific antibodies. A large amount of the alpha-chain was also found in the supernatant culture media at 72 h post infection and metabolic labelling with [35S] methionine indicated that it was proteolytically cleaved into a 32 kDa soluble form. A similar soluble or secreted form of the beta-chain was, however, not observed. Both receptor proteins were expressed on the surface of the insect cells as determined by flow cytometry analysis. Studies performed with the different IL-2 receptor forms (alpha- and beta-chains alone or in combination) in the presence or absence of rIL-2 suggest that the receptor proteins when expressed in infected insect cells are non-functional with respect to tyrosine phosphorylation. PMID- 8356403 TI - Leucocyte endothelial cell adhesion: a study comparing human umbilical vein endothelial cells and the endothelial cell line EA-hy-926. AB - EA-hy-926 is a cell line produced by hybridizing human umbilical vein endothelial cells (HUVEC) and the epithelial cell line A549. To establish whether EA-hy-926 could be used as a model for endothelial cells (EC) in leucocyte-EC adhesion interactions, the effect of interleukin-4 (IL-4), tumour necrosis factor (TNF) or interferon-gamma (IFN) stimulation on their adhesiveness and expression of E selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was compared with that of HUVEC and A549. Although HUVEC exhibited increased adhesiveness and adhesion molecule expression with IL-4, TNF or IFN, EA-hy-926 exhibited these responses only with TNF. CD11/CD18-dependent binding accounted for a significant component of basal binding to HUVEC and EA-hy 926, but did not account for the increased binding of T cells, JY, J6, ICH-BJ or ICH-KM cell lines to TNF-stimulated monolayers. At least part of the CD11/CD18 independent adhesion was attributable to VCAM-1 induction on HUVEC and EA-hy-926. TNF-stimulation also induced E-selectin expression on EA-hy-926 and HUVEC and an accompanying increase in neutrophil (PMN) binding. The EA-hy-926 cells used in this study, therefore, showed responses similar to HUVEC when stimulated with TNF but not when stimulated with IL-4 or IFN. PMID- 8356404 TI - Up-regulation by cyclosporine (CsA) of the in vitro release of soluble CD23 (sCD23) and of the in vitro production of IL-6 and IgM. AB - In the present study, we examined the effect of CsA on the in vitro production of Ig and on the in vitro production of molecules known to have B-cell growth and differentiation activities, such as IL-6 and sCD23. For the purpose of this study, we developed an experimental in vitro system closely resembling an in vivo model of ongoing B-cell activation. Pre-activated B cells proliferated and produced IgM optimally when they were re-cultured in the presence of IL-2/IL-6. CsA down-regulated the IL-2/IL-6-induced proliferative responses of pre-activated B cells by at least 50%, but it up-regulated IgM production in the same experiments. This up-regulating effect was not cytokine-related since it was also seen when cells were re-cultured in the absence of any cytokines. Optimal release of sCD23 was observed when SAC-pre-activated B cells were re-cultured in the presence of IL-4 or IL-4 plus IL-2 and CsA up-regulated significantly the release of this molecule in these cultures. Finally, CsA was shown to inhibit PHA-induced cell proliferation of PBMC and to up-regulate IL-6 production in the same cultures. We conclude that CsA can amplify in vitro both the production of Ig and the release of sCD23 by pre-activated B cells. This finding, in combination with the CsA-induced up-regulation of lectin-induced IL-6 production, may have clinical implications in disease states with an ongoing immune activation, where prolonged administration of CsA might be anticipated. PMID- 8356405 TI - Immunogenicity of HILDA/LIF either in a soluble or in a membrane anchored form expressed in vivo by recombinant vaccinia viruses. AB - Insertion of various cDNAs in the genome of the vaccinia virus (VV) enables the in vivo and in vitro study of the functional role and/or the immunogenicity of the virally encoded recombinant proteins. We have prepared a recombinant VV expressing the cDNA of the human cytokine HILDA/LIF (human interleukin for DA cells/leukaemia inhibitory factor), and used this virus to immunize mice against this protein, which is very homologous to its murine counterpart (approximately 80% homology). We also constructed and expressed by the same system a chimeric gene encoding the HILDA/LIF protein fused to the 37 COOH-terminal amino-acids of the human decay accelerating factor (DAF). This sequence proved to be sufficient for the targeting of the fusion protein to the cell membrane, where it is linked to the phosphatidylinositols. Both recombinant VVs induced cytokine-specific antibodies in mice as analysed with an ELISA where the recombinant HILDA/LIF was plastic-coated and a cytofluorometric assay where the LIF-DAF molecule was present at the cell surface of stably transfected P815. In the latter case HILDA/LIF remained biologically active suggesting that it was expressed in its native form. The LIF-DAF fusion protein was found to exhibit a better capacity to elicit an antibody response against the native form of the cytokine as detected in cytofluorometric assays. Whatever the recombinant virus used to immunize the mice, the MoAbs obtained were positive either in the ELISA or in the cytofluorometric assays but one, which suggested that the plastic coating induced a conformational change of HILDA/LIF. PMID- 8356406 TI - Occurrence of autoimmune diseases and relationship of autoantibody expression with HLA phenotypes in multicase rheumatoid arthritis families. AB - Presence of autoimmune diseases and relationship of autoantibody expression with HLA association has been studied in 44 multicase rheumatoid arthritis (RA) families of Asian Indian origin. An increased prevalence of systemic lupus erythematosus (SLE) was observed in relatives (2.3%). Although HLA-DR4 segregated preferentially with seropositivity in general, no difference was observed among seropositive versus seronegative RA. On the other hand, no HLA association was observed with ANF positivity in these families. An increased frequency of DR7 in the ANF negative and RF negative group of RA patients compared to positive groups suggests that it may act as protective element for the development of autoantibodies in RA. An increased occurrence of DR4 in relatives affected with SLE was observed. While RA segregated mostly with HLA-DR4 in these families, autoimmune thyroid disease and insulin dependent diabetes mellitus (IDDM) segregated with HLA-DR3 suggesting the involvement of at least two sets of HLA linked autoimmunity favouring susceptibility genes in the Indian population. PMID- 8356407 TI - Amyloidosis--incidence and early risk factors in patients with rheumatoid arthritis. AB - In a 15-year follow-up examination, reactive secondary amyloidosis (RSA) was found by subcutaneous fat biopsy in six out of 74 still living patients (8.1%) of an original population of 102 with erosive and seropositive rheumatoid arthritis (RA). Five of the 24 deceased patients had had RSA. Thus the 15-year incidence of RSA in RA was at least 10.9% (11/102). To study early prognostic aspects of RSA, comparison was made of 14 entry variables and the initial treatment in the RSA group (n = 11) and the control group (n = 81) respectively. At onset (< or = 6 months) of RA only serum orosomucoid, but after three years morning stiffness, ESR, serum CRP and orosomucoid were significantly worse in patients whom later developed RSA. Three out of 48 patients treated with gold sodium thiomalate and seven out of 30 treated with chloroquine developed RSA (p = 0.04). It is concluded that continuously active disease was the risk factor underlying RSA. The role of early chloroquine therapy is discussed. PMID- 8356408 TI - Polyclonal IgG anti-dsDNA antibodies exert cytotoxic effect on cultured rat mesangial cells by binding to cell membrane and augmenting apoptosis. AB - IgG anti-double stranded DNA antibodies (anti-dsDNA) purified from serum of patients with active systemic lupus erythematosus (SLE), have been found to be cytotoxic to the cultured rat mesangial cells (MC). In the present study, by use of immunofluorescent staining, immunoblotting, radioimmunoprecipitation, and cell cycle analysis, we showed that IgG anti-dsDNA could bind to the membrane of MC. The bound epitope was a 28 kDa protein, which would disappear if the cells were treated in advance with proteinase K (100 micrograms/ml). In addition, binding of MC by 20 micrograms/ml of anti-dsDNA IgG F(ab')2 activated plasma membrane (equivalent to 80 IU/ml of calf thymus double-stranded DNA binding activity) resulted in release of much more 3H-arachidonic acid than binding by 20 micrograms/ml of human IgG F(ab')2 (26.71 +/- 3.75% in the case of anti-dsDNA vs. 4.73 +/- 2.86% in the case of IgG). To understand further the cytotoxic mechanism of anti-dsDNA, we incubated MC with anti-dsDNA, for a variety of periods (from 10 minutes to 24 hours). After incubation, the cells were fixed and stained with hematoxylin-eosin for morphologic observation. Simultaneously, the genomic DNA was extracted and analyzed in 1.8% agarose gel electrophoresis. We found that cell death caused anti-dsDNA followed a process of apoptosis rather than necrosis. These results suggest that binding of anti-dsDNA with MC membrane may activate endonuclease which will fracture the DNA and lead to programmed cell death. PMID- 8356409 TI - Low serum vitamin D metabolites in women with rheumatoid arthritis. AB - The etiology of osteoporosis associated with rheumatoid arthritis (RA) is unknown. We studied the calcium and vitamin D metabolism in 143 women with RA (mean age 50.7 years). Albumin corrected serum calcium was normal. Serum alkaline phosphatase was increased in 29 percent of cases. Serum vitamin D levels were frequently very low. In 16 percent of the RA patients serum 25(OH)D concentration was below 12.5 nmol/L, which is arbitrarily considered as the limit of vitamin D deficiency osteomalacia. In the winter season 73 percent of the patients had serum 1,25(OH)2D levels below the seasonally adjusted normal range. The lowest values were found in patients with high disease activity. We suggest that there is a disturbance in vitamin D metabolism in RA. This might play a role in osteoporosis associated with RA. PMID- 8356410 TI - The recognition of rheumatoid arthritis in the eighteenth century. The contribution of Linne and Boissier de la Croix de Sauvages. AB - Linne and Boissier de la Croix de Sauvages, two botanists and physicians of the mideighteenth century, proposed systems for the classification of diseases. Their medical works have been examined for passages suggestive of rheumatoid arthritis (RA). References to gouty arthritis dominated in Linne's works. Sauvages described chronic joint diseases with affection of small and large joints which might have been RA. William Musgrave described similar cases in 1703. In a single passage in Linne's works such cases are also described. The conclusion is that RA probably has existed throughout the eighteenth century, and that its supposed emergence around the year 1800 is not well-founded. PMID- 8356411 TI - Total and free plasma and total synovial fluid piroxicam concentrations: relationship to antiinflammatory effect in patients with reactive arthritis and other arthritides. AB - Twenty-five patients (14 males, 11 females), sixteen with reactive arthritis and 9 with other arthritides were treated with piroxicam, 40 mg at day 1 and 20 mg daily the following 9 days. Both local knee joint and general disease activity were assessed at day 0 and day 10. At day 10, plasma and synovial fluid were drawn. Total and free (determined after equilibrium dialysis) plasma concentrations and total synovial fluid concentrations were measured by HPLC. Total plasma piroxicam concentrations (micrograms/ml) were 4.1 (0.5-8.3) [median (range)], free piroxicam plasma concentrations were 0.051 (0.012-0.118), total synovial fluid concentrations were 2.2 (0.3-4.6) and ratios total synovial to total plasma concentration were 0.51 (0.39-0.90). The effect of piroxicam treatment varied among the patients. We found no relationship between drug concentration and change in any of the disease activity parameters nor any correlation between the ratio of synovial fluid to plasma piroxicam concentration and the local knee joint disease activity parameters. PMID- 8356412 TI - Successful treatment of the anemia of rheumatoid arthritis with subcutaneously administered recombinant human erythropoietin. Slower response in patients with more severe inflammation. AB - We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease. PMID- 8356413 TI - Rifamycin SV versus triamcinolone in local treatment of rheumatoid synovitis. AB - This study was aimed to evaluate the usefulness of rifamycin SV as an agent for local treatment of rheumatoid synovitis. Rifamycin SV was compared with triamcinolone acetonide in a randomized controlled trial on 87 patients with rheumatoid arthritis and with persistent knee synovitis. The treatment with rifamycin consisted of several weekly intra-articular injections, whereas triamcinolone was given as a single intra-articular injection. At the end of the therapy, 27 (61.4%) of the 44 rifamycin patients and 39 (91%) of the 43 steroid patients responded well to the treatment, and this difference was significant (p < 0.01). Rifamycin SV was responsible for unpleasant local side effects in all cases. In both groups, after 1 year of follow-up the synovitis had relapsed in about 42% of cases. We conclude that rifamycin SV is less useful than triamcinolone acetonide in the local treatment of rheumatoid synovitis. PMID- 8356414 TI - Verrucous endocarditis and sicca syndrome. PMID- 8356415 TI - Use of unconventional remedies for arthritis in Brazil. PMID- 8356416 TI - Lack of effect of recombinant alpha interferon in the treatment of rheumatoid arthritis. PMID- 8356417 TI - [3 reports of success]. PMID- 8356418 TI - [Dental caries (DMFT) in adults in Switzerland 1988]. AB - In 1988, 864 adults were examined for dental and periodontal conditions in 47 dental offices in Switzerland according to WHO methods. Among the 57 offices selected at random 10 dentists were unwilling to cooperate. Within each office, 36 patients were chosen by a randomizing mechanism. 51 percent of the selected patients presented themselves for the examination whereas 14 percent refused to participate in the study; of the remaining subjects one third could not be reached during the three to five days available for contacting them and two thirds were unable to come to the respective dental office at the preset day of examination. The DMF data obtained were similar to the results of previous local surveys, part of which were based on random samples. Up to age 74, it was concluded that the data of the present survey are fairly representative of the Swiss resident population. In the age group 75 and above, the number of missing teeth (MT) was too low, mainly due to edentulous persons, institutionalized and other, being obviously underrepresented. The Swiss DMFT of 22.3 in the age group 35-44 was almost the highest mean among 26 European countries. However, prevention efforts at school age, already obvious in the age group 30-34, will substantially improve the results at age 35-44 by the year 1998. The number of DT was 1.0 and 1.3 for the ages up to 29 and below 1.0 in the older groups. Up to age 54, FT was the most important component of the DMFT while in the older groups, MT was highest. PMID- 8356419 TI - Microstructure and strength analysis of ultrasonically shaped ceramics. AB - In this study, the influence of a new ultrasonic shaping procedure on the surface quality, microstructure, bending strength and fatigue behaviour of a feldspathic porcelain was investigated. A total of 120 standardized (ISO 6872) autoglazed, ground, lapped and ultrasonically machined porcelain test bars were analyzed. Another 24 equiformat experimental alumina ceramics, which were ultrasonically machined, as well as 24 nontreated fload glass specimen served as controls. It could be shown that the porcelain removal process with diamond grinding wheels yielded a rough surface microrelief and lead to structural subsurface damage, decreasing bending strength and fatigue behaviour. In contrast, ultrasonic shaping resulted in a smoother surface and prevented damage to the subsurface layer of the machined brittle porcelain, although, the smoothest surfaces were achieved by lapping. Both bending strength and fatigue behaviour of the conventional dental porcelain were increased by ultrasonic machining. However, the fracture toughness of the experimental alumina was substantially higher and was not subjected to a decrease in fatigue. PMID- 8356420 TI - [Efficiency and margin quality in the computer-assisted molding and grinding of ceramic inlays]. AB - The life of diamond-coated discs during CAD/CAM machining of ceramic inlays was evaluated using the standard hydro-drive (H) and an electric drive (E) as a part of the Cerec 3rd generation unit. E-drive discs (40 mm diameter, 0.5 mm thickness) with four experimental diamond coatings, i.e. different grain sizes, E126 (106-125 microns), E64 (53-63 microns), E46-3 (38-45 microns; triple coating), E46-1 (38-45 microns; single coating) were used. The standard H-drive disc (30 mm diameter, 0.3 mm thickness) and H126 (106-125 microns) coating were used as a control. The same standard mesio-occluso-distal molar inlay was machined from blocks (size 1-8) of Dicor MGC light glass-ceramic and of Vita MkII feldspathic fine porcelain as many times as possible with one disc in each group and the number of machined inlays per disc was counted. Additionally the edge roughness (Ra) of the machined inlays was measured using a Talysurf 50 instrument. The numbers of inlays machined with H126 were 21 porcelain/12 glass ceramic inlays. The numbers of inlays machined from porcelain/glass-ceramic with the E-drive test discs were E126: 180/68; E64: 93/29; E46-3: 80/21 and E46-1 (current limited to 2.5 ampere): 44/19 inlays. The edge roughness of porcelain/glass-ceramic inlays machined with the E-drive discs was significantly lower than the roughness of inlays machined using the H-drive. E126: 16% (p < 0.05)/43% (p < 0.001); E64: 49%/66%; E46-1: 62%/73%; E46-3: 83%/87% (all differences p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356421 TI - [Food-induced granuloma of oral tissues]. PMID- 8356422 TI - [Impression and registration methods for difficult complete-denture cases]. PMID- 8356423 TI - [Dental filling materials/amalgam. The joint statement of the university dental institutes of Switzerland and of the Swiss Dental Society]. PMID- 8356424 TI - Is a healthy diet always healthy? PMID- 8356425 TI - Percutaneous endoscopic gastrostomy (PEG): a major advance in enteral feeding. PMID- 8356427 TI - Dental disease, fibrinogen and white cell count; links with myocardial infarction? AB - Plasma fibrinogen and white blood cell count were compared in fifty patients aged 25-50 years with periodontal disease and in fifty age-matched controls with relatively healthy periodontal tissues. Patients had significantly higher levels of fibrinogen and white cell count, and dental indices correlated significantly with these two cardiovascular risk factors on multivariate analyses. We suggest that inflammatory dental disease may be a determinant of fibrinogen level and white cell count in the general population, and that fibrinogen and white cell count may be two mediators of the link between dental disease and myocardial infarction. PMID- 8356426 TI - Minimal change nephropathy in the west of Scotland: a review of sixty-four patients. AB - Sixty-four patients with a histological diagnosis of minimal change nephropathy have been followed for a median of 110 months. Patients transferred from paediatric units (11%) had a worse prognosis in that all became frequent relapsers. Patients who relapsed within three months or who went on to become frequent relapsers had a higher 24 hour urine protein excretion at presentation than patients who did not relapse. After fifteen months of remission relapse was rare; 97% of those who relapsed did so within 36 months. Patients who have been off steroids and proteinuria free for 36 months might therefore be considered cured. PMID- 8356428 TI - An audit of the activities of the paediatric oncology unit in Edinburgh, 1982 1991. AB - The activities of the paediatric oncology unit at the Royal Hospital for Sick Children, Edinburgh during 1982-1991 were audited. There were 254 new patients of whom 240 had a malignancy, seven had Langerhans cell histiocytosis and seven had non malignant tumours. Of the 254,131 (52%), 78 (31%), 14 (65), were normally resident within the Lothian, Fife and Borders regions respectively. Therefore, although the unit is a part of the Lothian Health Board, it is in practice, the referral centre for S.E. Scotland. A majority (92%) of patients were treated according to national or international protocols during the last five years and of the 240 children diagnosed to have cancer, 158 (66%) are at present in clinical remission. These figures compare favourably with national averages for protocol compliance and survival. During these ten years, an additional 69 children with cancer from S.E. Scotland were treated at other centres. Therefore, while the unit justifies its existence it has yet to realise its full potential. PMID- 8356429 TI - When should patients with bacterial meningitis be referred to a neurosurgical unit? AB - The case records of 97 patients with proven bacterial meningitis who were referred to a regional neurosurgical unit between 1964 and 1991 were reviewed. Mortality declined from 34% in the first cohort referred between the years 1964 82 to 5% for 1983-91 (X2 = 11.78; p < 0.001). Fewer patients were admitted in coma, (X2 = 4.43; p < 0.05), or with focal neurological signs (X2 = 7.57; p < 0.01) in the second cohort. The rate of referral increased in the later period but the incidence of unsuspected brain abscess (16% and 15%) did not change. There was a strong correlation between coma on admission and death, (X2 = 17.3; p < 0.001) and with brain abscess and death (X2 = 6.73; p < 0.01). In conclusion patients with known or suspected bacterial meningitis coupled with a decreasing level of consciousness or focal neurological signs should be referred to a neurosurgical centre. PMID- 8356430 TI - Defibrillation by general practitioners: an audit of resuscitation in a Scottish rural practice. AB - The objective was to review the outcome of resuscitation attempts in a small remote two-partner practice of 2700 patients in Galloway, South West Scotland during the period 1985-1992. During the study period 15 attempts were made to resuscitate the victims of cardiac arrest. Two sub-groups were identified. In the first, nine out of ten patients whose arrest occurred in the presence of a doctor were successfully resuscitated and all proved to be long term survivors. In the second group of five patients whose arrest took place before the arrival of the doctor there were no survivors. We conclude that defibrillation by general practitioners has a valuable contribution to make in reducing the mortality from myocardial infarction in rural practice. PMID- 8356431 TI - Pasteurella multocida abscess complicating a femoral vein thrombosis. PMID- 8356432 TI - A patient with neurosyphilis presenting as chorea. AB - Despite the marked decline in frequency of neurosyphilis over the past three decades in the United Kingdom, new cases continue to appear both sporadically and as a complication of HIV infection. There is clinical evidence that neurosyphilis is becoming less typical. We describe a case of neurosyphilis presenting predominantly with choreoathetosis and associated hemiparesis in an otherwise healthy, immunocompetent patient. Only six cases of neurosyphilis presenting with features of basal ganglia damage have been reported in the recent literature, five of whom had HIV infection. PMID- 8356433 TI - Reflections on Dr Henderson of Perth's case of impracticable labour: an early case (1820) in which the caesarean operation was performed. AB - The rediscovery of a female pelvis with features characteristic of osteomalacia stimulated an enquiry into the clinical history of the woman involved. It was established that she died in 1820, aged 30. Despite being severely debilitated and confined to bed for some years with increasing skeletal deformities, she became pregnant, and in due course laboured unsuccessfully for about 102 hours. An elective caesarean section was performed, but she died some hours later, though her daughter survived and was appropriately christened Caesar Anna. This represents one of the earliest cases in which the caesarean operation was performed where the full obstetric history was carefully recorded by the obstetrician involved, Dr. Henderson of Perth. The case was clearly considered important, and in 1836 engravings of this pelvis were used to illustrate Professor Hamilton's "Practical Observations of Various Subjects Related to Midwifery". Such cases are now of great rarity in the developed world. PMID- 8356434 TI - Recent developments in secondary prevention of stroke. PMID- 8356435 TI - Models of health care for stroke. PMID- 8356436 TI - Management of change in the NHS. PMID- 8356437 TI - Cost of stroke. PMID- 8356439 TI - Developments in acute stroke care. PMID- 8356438 TI - Recent developments in primary prevention of stroke. PMID- 8356440 TI - Three good choices. PMID- 8356441 TI - "Critical fat". PMID- 8356442 TI - The true cost of a free AIDS vaccine. PMID- 8356443 TI - Misconduct: views from the trenches. PMID- 8356444 TI - Innovative techniques on display at Boston meeting. PMID- 8356445 TI - Putting antibodies to work inside cells. PMID- 8356446 TI - Frog venom cocktail yields a one-handed painkiller. PMID- 8356447 TI - Is NIH's crown jewel losing luster? PMID- 8356448 TI - Life history variables preserved in dental cementum microstructure. AB - The age and season of death of mammals, as well as other aspects of their life history, can be estimated from seasonal bands in dental cementum that result from variations in microstructure. Scanning electron micrographs of goats fed controlled diets demonstrate that cementum bands preserve variations in the relative orientation of collagen fibers that reflect changes in the magnitude and frequency of occlusal forces from chewing different quality diets. Changes in the rate of tissue growth are also reflected in cementum bands as variations in the degree of mineralization. PMID- 8356449 TI - Deletion of the paired alpha 5(IV) and alpha 6(IV) collagen genes in inherited smooth muscle tumors. AB - The gene encoding alpha 6(IV) collagen, COL4A6, was identified on the human X chromosome in a head-to-head arrangement and within 452 base pairs of the alpha 5(IV) collagen gene, COL4A5. In earlier studies, intragenic deletions of COL4A5 were detected in a subset of patients with Alport syndrome (AS), a hereditary defect of basement membranes. In some families, AS cosegregates with diffuse leiomyomatosis (DL), a benign smooth muscle tumor diathesis. Here it is shown that patients with AS-DL harbor deletions that disrupt both COL4A5 and COL4A6. Thus, type IV collagen may regulate smooth muscle differentiation and morphogenesis. PMID- 8356450 TI - Identification of a structural glycoprotein of an RNA virus as a ribonuclease. AB - One of the three structural glycoproteins of classical swine fever virus (CSFV) is E0, a disulfide-bonded homodimer that induces virus-neutralizing antibodies and occurs in a virion-bound as well as a secreted form. E0 was shown to be similar to a family of fungal and plant ribonucleases. Purified E0 from CSFV infected cells was a potent ribonuclease specific for uridine and inhibitable by zinc ions. PMID- 8356451 TI - Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes. AB - During the assembly of immunoglobulin and T cell receptor variable region genes from variable (V), diversity (D), and joining (J) segments, the germline-encoded repertoire is further diversified by processes that include the template independent addition of nucleotides (N regions) at gene segment junctions. Terminal deoxynucleotidyl transferase (TdT)-deficient lymphocytes had no N regions in their variable region genes, which shows that TdT is responsible for N region addition. In addition, certain variable region genes appeared at increased frequency in TdT-deficient thymocytes, which indicates that N region addition also influences repertoire development by alleviating sequence-specific constraints imposed on the joining of particular V, D, and J segments. PMID- 8356452 TI - Mice lacking TdT: mature animals with an immature lymphocyte repertoire. AB - In adult animals, template-independent (or N) nucleotides are frequently added during the rearrangement of variable (V), diversity (D), and joining (J) segments of lymphocyte receptor genes, greatly enhancing junctional diversity. Receptor genes from adult mice carrying a mutation in the terminal deoxynucleotidyl transferase (TdT) gene have few N nucleotides, providing proof that this enzyme is essential for creating diversity. Unlike those from normal adults, receptor genes from adult mutant mice show extensive evidence of homology-directed recombination, suggesting that TdT blocks this process. Thus, switch-on of the TdT gene during the first week after birth provokes an even greater expansion of lymphocyte receptor diversity than had previously been thought. PMID- 8356454 TI - Fibrinogen: its role in the hemostatic regulation in atherosclerosis. AB - Numerous epidemiologic studies have clearly shown that high plasma fibrinogen levels are strongly correlated with the frequency of myocardial infarction, stroke, and peripheral atherosclerosis. These data indicate that measurements of fibrinogen should be included in cardiovascular risk factor profiles. Since thrombosis is recognized as the central mechanism of these atherosclerotic complications, it seems advisable to accept the predictive value of this protein. Fibrinogen is involved in platelet aggregation, blood rheology, and endothelial cell injury, which are thought to play a key role in thrombogenesis. Fibrinogen may predict bypass occlusion but appears to have no significant influence on restenosis following successful coronary angioplasty. Furthermore, fibrinogen represents an acute-phase protein, being of no specificity. Its level varies genetically, as well as circadian and seasonal variations, and is influenced by a number of circumstances and drugs. Plasma levels of fibrinogen decrease by life style changes, smoking cessation, and different medications such as fibrates, but the risk-lowering effect is not proven yet. PMID- 8356453 TI - Genotypic and phenotypic characterization of HIV-1 patients with primary infection. AB - Better characterization of human immunodeficiency virus-type 1 (HIV-1) in patients with primary infection has important implications for the development of an acquired immunodeficiency syndrome (AIDS) vaccine because vaccine strategies should target viral isolates with the properties of transmitted viruses. In five HIV-1 seroconverters, the viral phenotype was found to be uniformly macrophage tropic and non-syncytium-inducing. Furthermore, the viruses were genotypically homogeneous within each patient, but a common signature sequence was not discernible among transmitted viruses. In the two cases where the sexual partners were also studied, the sequences of the transmitted viruses matched best with minor variants in the blood of the transmitters. There was also a stronger pressure to conserve sequences in gp120 than in gp41, nef, and p17, suggesting that a selective mechanism is involved in transmission. PMID- 8356455 TI - Blood cell activation: new perspectives from ultrastructural morphometry. AB - The new computerized approaches for image analysis available for a few years permit, in an excellent and detailed way, monitoring cellular structural modifications during activation processes. Here, we presented morphometric data obtained on blood cells (platelets, monocytes, and PMN cells) after in vitro activation and under in vivo conditions related to atherosclerosis studied by means of electron microscopy. Area and perimeter form factors, nucleus to cytoplasma area ratio, and the surface density of platelet plasma membrane openings of SCCS presented significant differences compared with the respective significant differences compared with the respective controls. Ultrastructural markers of blood cell activation were revealed by the computerized morphometry applied on ultrastructural images. PMID- 8356456 TI - Hypercholesterolemia and platelets. PMID- 8356457 TI - Platelets in diabetes: the role in the hemostatic regulation in atherosclerosis. AB - Vascular diseases and related complications still represent the main cause of death in diabetic patients. Neuropathy, nephropathy, retinopathy, and disturbed nutritive tissue perfusion may result from reduced capillary microcirculation. These disturbances are diabetes specific. Macroangiopathy does not differ structurally from atherosclerotic lesions of nondiabetic subjects, but leads to accelerated cerebral, coronary, and peripheral artery disease. Occurrence of life terminating thrombotic events, which are superimposed on those vascular lesions, are increased. Thus, morbidity and mortality of diabetics depend mainly on vascular complications. Normal blood flow is a prerequisite of adequate organ perfusion and results from vasomotion, plasma components, corpuscular blood elements, vascular architecture, and the undisturbed interaction of these components at the endothelial interface. Functional thromboresistance of the endothelial layer is reduced in the diabetic state. Increased intravascular thrombin generation, reduced fibrinolytic potential, and hyperactive platelets lead to a prethrombotic state. This thrombotic diathesis increases the permanent danger of acute flow interruption. Activated platelets operate by three mechanisms: (1) Microembolization of the capillaries; (2) local progression of preexisting vascular lesions by secretion of constrictive, mitogenic, and oxidative substances; (3) trigger of the prognosis-limiting arterial thrombotic event. We were able to show that the increased functional properties of diabetic platelets result from the primary release of larger platelets with enhanced thromboxane formation capacity and increased numbers of functional glycoprotein receptors GPIb and GPIIb/IIIa, which are synthesized in the megakaryocytes. The megakaryocyte-platelet system is turned on in diabetes mellitus. It could be demonstrated with the Duesseldorf III method of flow cytometric activation marker testing (CD62, CD63, thrombospondin) that predominantly large platelets circulate in an activated state in diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356458 TI - Omega-6 and omega-3 essential fatty acids in atherosclerosis. PMID- 8356459 TI - Lipoproteins and prostacyclin stability. AB - PGI2 is an important local mediator keeping circulating blood cells apart from the vessel wall, thus regulating hemostasis. Alterations of locally available amounts of this compound may be associated with either bleeding or thrombotic events. Factors influencing synthesis, transmission, and degradation coregulate the amount of biologically active PGI2 available at a certain vascular site. Plasmatic T1/2 of PGI2 is shortened either due to an inherited disorder or an acquired disease, its underlying cause being unknown. Generally, this is associated with thrombotic events and extremely low concentrations of both HDL cholesterol and apoA1. In contrast, the only patient we saw with a prolonged PGI2 T1/2 repeatedly experienced extremely severe bleeding complications. Recovery from severe diseases such as shock and malaria, for example, results in normalization of both PGI2 T1/2 and lipoprotein (HDL) and apoA values. Although these findings have not yet been verified at a molecular level, it is likely, that apoA1 contributes to the stabilization of PGI2 in human blood, thus representing one further link between lipid metabolism and hemostasis. PMID- 8356460 TI - 13,14-Dihydro-prostaglandin E1 in atherosclerosis. PMID- 8356461 TI - Altering vessel wall fatty acid metabolism: a new strategy for antithrombotic treatment. PMID- 8356463 TI - Heparin, polycations, and atherosclerosis. PMID- 8356462 TI - Endothelium-derived nitric oxide, endothelin, and platelet vessel wall interaction: alterations in hypercholesterolemia and atherosclerosis. AB - The endothelium modulates vascular tone by releasing NO, which is a potent vasodilator and inhibitor of platelet aggregation. Thus, the endogenous nitrate has an important protective role in preventing vasospasm and thrombus formation. In addition, the endothelium is a source of contracting factors, such as endothelin-1. Due to its strategical anatomic position, the endothelium is a primary target for injurious stimuli and cardiovascular risk factors. Oxidized LDL reduce the endothelial production of NO and enhance that of endothelin-1. The same pattern of endothelial dysfunction occurs in hypercholesterolemia and in part in atherosclerosis. These alterations of endothelial function may contribute to vasospasm and thrombus formation, which are common events in patients with atherosclerosis. PMID- 8356464 TI - Hemorheology, thrombogenesis, and atherosclerosis. PMID- 8356465 TI - [A study of transpial migration of implanted serotonergic neurons in rat spinal cord]. AB - Transpial migration of implanted 5-HT neurons from the subarachnoid space into the spinal cord was studied in adult Wistar rats. Embryonic raphe tissue or cell suspension containing 5-HT cells was used as grafts. The implanted 5-HT cells were monitored by 5-HT immunohistochemical method. The results are as follows: (1) 10 d after cutting the spinal cord at lower thoracic level, 5-HT fibers disappeared in the transected spinal cord. (2) Raphe tissue was implanted into the subarachnoid space of the thoracic lumbar segment after the spinal cord was cut. One month later, 5-HT positive cells could be found in the transected spinal cord with fibers extending into both the grey and the white matters. (3) If the raphe cell suspension instead was implanted, a number of 5-HT positive cells appeared in the grey matter near the implanted region and the distribution of these cells in the grey matter was quite consistent with the implanted range of the cell suspension in the subarachnoid space. The 5-HT positive cells which had entered into the spinal cord sent out fibers and reestablished a new fiber network in the grey matter. (4) After implantation, the number of the 5-HT positive fibers in the transected grey matter became more and more sparsely distributed with increasing distance from the cell bodies and the 5-HT positive fibers reappeared in the white matter were much less than that in the grey matter. Present results show that the implanted 5-HT neurons are able to migrate transpially from the subarachnoid space into the spinal cord. PMID- 8356466 TI - [Effects of 6-OHDA lesions of the bilateral dorsal noradrenergic bundle on learning-dependent long-term synaptic potentiation in dentate gyrus]. AB - In the present study, the role of NE in learning-dependent long-term potentiation (LdLTP) was investigated by examining the effects of 6-hydroxydopamine (6-OHDA) lesion made in the bilateral dorsal noradrenergic bundle on the changes of synaptic efficacy in dentate gyrus (DG) and related conditioned response during drinking conditioning. Bilateral injection of 6-OHDA (12 micrograms/4 microliters) into the dorsal noradrenergic bundle caused a continuous decrease of the amplitude of population spike (PS) reaching a value of 50 +/- 6.3% and 28 +/- 6.4% respectively at the 6th and the 12th day after injection of the drug. During this period of 7 days, the LdLTP could not be produced in spite of 20 trainings per day for a total of 140 trials, and the conditioned drinking response could not be established. The above results indicate that normal levels of norepinephrine in the hippocampus are necessary to the establishment of LdLTP in the DG and suggest that the development of LdLTP in the DG may be modulated by the nucleus locus ceruleus via the dorsal noradrenergic bundle. PMID- 8356467 TI - [Measurement of the single muscle fiber action potentials and jitter value in tibialis anterior muscles of rabbits in situ]. AB - With a home-made jitter data processing board and microcomputer for recording extracellular single fiber action potential (SF-AP), variations of the time intervals of the SF-AP pairs, or the jitters, from two adjacent muscle fibers in the unique motor unit in tibialis' anterior in response to repeated stimuli were measured. The jitter distribution of 936 recorded from 7 rabbits was positively showed with a percentile value of P75-P25 of 54.99-14.61 microseconds. The data suggested that the lower limit was smaller than that of skeletal muscles in normal human and that there exists also some differences in the jitter values of SFEMG between human and rabbit muscles. PMID- 8356468 TI - [Expression of left ventricular ANF-gene in rat with cardiac hypertrophy]. AB - Plasma concentration of ANF and expression of left ventricular ANF-gene in rats with cardiac hypertrophy induced by abdominal aortic partial ligation were analyzed by RIA and Northern blot respectively. Results showed that plasma concentration of ANF and level of left ventricular ANF-mRNA in cardiac hypertrophic rats increased markedly, indicating that the cardiac load may induce transcription and expression of left ventricular ANF-gene. This effect could be potentiated by intracellular calcium modulator taurine and inhibited by vasodilator hydralazine. PMID- 8356469 TI - [Modulating effects of nucleus termination nervi trigemini on the activities of genioglossus in rabbits]. AB - The effects of electrical stimulation to the nucleus termination nervi trigemini (NTV) on the activities of genioglossus were studied in 35 rabbits anesthetized with urethane. Electrical stimulation of NTV could cause facilitatory response of genioglossal muscle markedly. Monosodium glutamate microinjected into NTV also produced significant increase of genioglossal activities. The latency of genioglossal response to electrical stimulation of dorsal or ventral part of NTV were respectively 5.9 +/- 0.7 ms and 3.0 +/- 0.4 ms. When the nucleus hypoglossus was stimulated, the latency was 2.2 +/- 0.2 ms. These results suggested that the excitation of NTV could enhance the genioglossal activities so that the resistance of upper airway might be decreased. PMID- 8356470 TI - [Descending cord dorsum potentials evoked by stimulation at "Yong Quan" acupoint]. AB - Segmental spinal cord potential (Y-sCDP) evoked by stimulation at "Yong Quan" acupoint of Sprague-Dawley rat vanished gradually when the recording electrode was moved rostrally along the dorsal surface of the spinal cord. When the recording electrode was placed more rostrally, for example at C6, another positive slow potential, Y-dCDP, could be recorded. Y-dCDP disappeared completely when the spinal cord had been sectioned at a higher cervical level. Electrolytic lesions of ventral periaqueductal gray (PAG) could also decrease remarkably the amplitude of Y-dCDP. This facet suggests that the PAG, an analgesia related nucleus, is involved in the generation of Y-dCDP induced by stimulation at "Yong Quan" acupoint. PMID- 8356471 TI - [Changes of calcium transport capacity of myocardium and myocardial mitochondria during sepsis]. AB - On the isolated perfused heart model of septic rats, the present study showed that: (1) Calcium content and 45Ca-influx of myocardium increased 190%, 208% (P < 0.01) and that of mitochondria elevated 332%, 178% (P < 0.01) respectively with no change of myocardial 45Ca-release during sepsis. (2) 10(-8) mol/L calcitonin gene-related peptide (CGRP) or 10(-7) mol/L atriopeptin (ANP) added into the Krebs-Henseleit solution could effectively reduce 45Ca-influx to myocardium and mitochondria with no effect on myocardial 45Ca-release. (3) The calcium uptake reserve of mitochondria evaluated in vitro showed that the maximal calcium uptake and uptake velocity of mitochondria during sepsis were reduced 34.6%, 33.3% (P < 0.01) respectively. The data suggested that the net increase of myocardial Ca2+ content resulted from increase of 45Ca-influx with no change of 45Ca-efflux and the reduction of mitochondrial Ca2+ buffering capacity during sepsis were key events in the pathogenesis of intracellular Ca(2+)-overload. CGRP and ANP could effectively alleviate Ca(2+)-overload of myocardium and mitochondria. This may have some cellular protection action during sepsis. PMID- 8356472 TI - [Effect of electrical stimulation of hyperstriatum on nucleus dorsalis intermedius ventralis anterior thalami somatosensory units in pigeon]. AB - Discharges of 88 somatosensory units in the nucleus dorsalis intermedius ventralis anterior thalami (DIVA) in response to afferent impulses of radial nerve on 55 urethane anesthetized pigeons were recorded and analysed. Among the 88 units, part of them also responded to the stimulation of sciatic nerve. Following electrical stimulation of somatic projecting area of hyperstriatum, the spontaneous discharges and the responses of DIVA somatosensory units to radial inputs were obviously inhibited and the degree of inhibition was linearly correlated with the frequency and intensity of stimulation. The inhibitory effect on the responses to radial inputs may cause an increase in latency and a decrease in number of spikes. These results indicate that the DIVA certainly belongs to somatosensory system, and the somatic projecting area of hyperstriatum has a descending inhibitory effect on the DIVA somatosensory units. The hyperstriatum may thus exert feedback control over its sensory inputs through descending inhibition. It appears that the functional connection between the highest region of central nervous system and thalamus in avian is similar to that of mammal. PMID- 8356473 TI - [Changes of Leu-enkephalin in striatum and hypothalamus of rats during hyperbaric oxygen exposure]. AB - The purpose of this study is to investigate the changes of Leu-Enkephalin (L-Enk) content in striatum and hypothalamus of rats during hyperbaric (HBO) oxygen exposure. Thirty-two male rats in the experiment were randomly divided into four groups: normobaric air group, normoxic hyperbaric nitrox group, nonconvulsion HBO group and convulsion HBO group. L-Enk content in striatum and hypothalamus was determined by radioimmunoassay. The results show that L-Enk content in the striatum and hypothalamus of rats exposed to hyperbaric oxygen environment were markedly higher than that of rats exposed to normobaric air and normoxic hyperbaric nitrox. The experimental results suggest that the elevation of L-Enk content in striatum and hypothalamus shows a positive relationship with the HBO exposure duration of animals and that there was no marked relationship with normoxic hyperbaric nitrox environment and compression-decompression method. PMID- 8356474 TI - [Glucocorticoid receptor-like antigen on neuronal plasma membrane of rat brain]. AB - The existence of glucocorticoid receptor-like antigen on the synaptic plasma membrane (SPM) isolated from rat brain was demonstrated by ABC-gold technique. The SPM was first incubated with McAb 250 (a monoclonal antibody to the glucocorticoid receptor) and then biotinylated horse-anti-mouse IgG and streptavidin-gold (SAG) was added in proper order to the reacting system. The gold particles could be visualized on the external surface of neuronal processes under electron microscope. This is the first morphological demonstration of the existence of glucocorticoid receptor-like antigen on neuronal membranes. PMID- 8356475 TI - [A method for repairing the tip of tungsten-in-glass microelectrode]. AB - When glass insulating tungsten microelectrodes are made, the insulating glass is usually drawn apart at an earlier than desired moment leaving a longer uninsulated metallic tip. A simple method for removing the excessively protruded part of the tungsten tip and triming it to any desirable length and shape is described. PMID- 8356476 TI - [A model for perfusing the carotid body in the awake goat and its evaluation]. AB - A model for perfusing the carotid body (CB) in the awake goat was described in detail. The main surgical procedures were: (1) to ligate the occipital artery, cut the carotid sinus nerve and excise the CB on one side; (2) to rearrange some arteries, which supply the brain and neck on the other side (perfusion side), for isolating the CB; (3) to place cannulae in the jugular vein and the carotid artery for drawing blood and perfusing the intact CB on the perfusion side. Perfusion of the CB with goat own blood can be carried out via an extracorporal circuit during the experiment. The remark able advantages of this perfusion model are: (1) the animal can be kept in a normal physiological condition; (2) the arterial gases and pH in the CNS and CB can be controlled separately. The NaCN test was done in three steps to evaluate the model by judging the sensitivity of the peripheral chemoreceptors including the aortic and perfused carotid bodies. Applications of this model were also discussed. PMID- 8356477 TI - Anthropological perspectives on chronic illness. Introduction. PMID- 8356478 TI - 'High-pertension'--the uses of a chronic folk illness for personal adaptation. AB - Chronic illness exerts a lasting and pervasive influence on personal experience of the world. It is commonly viewed as a phenomenon to be coped with, requiring an adaptive response on the part of an individual. Chronic illness, however, is a culturally-influenced tool which in itself can be used to organize and implement an adaptive response to personal experience. Employing Hallowell's concept of the self in the behavioral environment, the uses of a chronic folk illness, 'high pertension', for personal adaptation are discussed. Data from research on health beliefs about hypertension and illness behavior in a sample of 60 older African American women in New Orleans are presented. 'High-pertension', a chronic folk illness related to the biomedical 'hypertension', and involving blood and 'nerves', is described. Health beliefs and illness behavior associated with high pertension are considered as part of an individual's total effort at adaptation within the behavioral environment. These points are made: (1) Chronic illness can be used as a means to express one's self in relation to the behavioral environment. (2) Chronic illness can be used to manipulate and manage the relation of self to environment. (3) Chronic illness can be used to legitimize and announce role change. These uses are available to the individual by virtue of social interaction, cultural precedent and the chronicity and meaning of the illness itself. For persons in a severely stressed, constrained, and disadvantaged social position, as are many older African-American women, chronic illness offers one of the few means of controlling the behavioral environment available to the individual. Although in anthropology and biology we speak of adaptation in terms of human groups, we are ultimately considering person environment fit, that is, personal adaptation. Chronic illness can be a part of a culturally-influenced adaptive response. PMID- 8356479 TI - Redefining health: living with cancer. AB - The patients presented in this paper were being treated for cancer. None denied the diagnosis, and all were adhering to the medical regimen. Yet these patients also said that they were healthy in the face of the implications of their disease and the physical toll imposed by the treatments. The definition of health currently used by the American health care system is too restrictive to encompass the perception voiced by these individuals. This paper proposes to broaden the concept of health to help provide a legitimate place in society for individuals with chronic, life-threatening illnesses. A theoretical framework is proposed which might explain how these patients could still see themselves as healthy despite their disease. The core concept of health in this model is a sense of self-integrity, and the construct of health has two dimensions, Physical Status and Social Function. Individuals with chronic, life-threatening diseases like cancer use both of these dimensions simultaneously in order to negotiate and reestablish a sense of self-integrity based on their continued social functioning even in light of their acknowledged physical condition. Implications for restructuring our thinking about health, disease, and the mechanisms used to cope with cancer are outlined in order to develop a more realistic definition of health which is contextually based in the lives of the individuals with the disease. The criteria for assessment would not be biologic integrity alone, but a complex compromise between personal needs, social obligations, and physical abilities. PMID- 8356480 TI - The dilemma of seeking urgent care: asthma episodes and emergency service use. AB - Asthma is an invisible and unpredictable chronic illness characterized by recurrent episodes of airflow obstruction and airway inflammation. Until recently, psychological factors were thought to play a major role in this condition. The notion of an emotionally-based illness serves to discredit asthma as a 'real' illness among health professionals and patients alike, contributes to the sense of stigma that persons who have asthma experience, and impedes effective management. Findings from research with a sample of 95 adults with physician diagnosed and documented asthma indicate that persons who have asthma walk a tightrope between delaying formal medical intervention and seeking treatment too soon. Uncertainty about the quality and speed of care available in an emergency department shapes, in part, the nature of the lived experience of asthma and affects feelings of control over the illness. These concerns create a push-pull dynamic, as individuals struggle to make decisions about emergency department use that will provide relief, ensure autonomy, deter the experience of stigma, and diminish the threat of death. PMID- 8356481 TI - Self-care and multiple sclerosis: a view from two cultures. AB - The role of self-care in the management of chronic illnesses is essential to successful patient care. This paper compares and contrasts self-initiated self care practices of 51 Danish and 35 American persons with multiple sclerosis at various levels of disability. Respondents were asked about ways they managed their symptoms and problems during periods of non-medical contact--including methods of following the medical regimen; alternative treatments; use of lay referral systems; and, sources of information regarding physical, psychological, social, and environmental dimensions of coping with the illness. The two groups of respondents varied regarding adaptation strategies and primary sources of information used. The ultimate aim, however, of using these strategies was similar; to gain control over uncertainty, dependency, and physical and emotional decline. This study suggests that the empowering role of self-initiated self-care strategies in chronic illness may transcend differences in health care systems. PMID- 8356482 TI - Life stress, social support and clinical depression: a reanalysis of the literature. AB - In recent years, theorists and researchers have disagreed about the relationship between social support and mental health. Some believe that support is a direct provoking agent (i.e. lack of support constitutes strain), whereas others maintain that support is a vulnerability factor moderating the effect of life stress. Focusing on clinical depression, the article reviews the arguments and evidence supporting a strain hypothesis of social support versus a vulnerability hypothesis. Reanalyzing cross-classified data from 12 community studies of clinical depression, the study shows that the choice of model depends on the specification of functional form of the stress-clinical depression relationship. The linear probability specification suggests a vulnerability hypothesis, whereas the logit and probit specifications support a strain hypothesis. However, theoretical and statistical arguments tend to favor a logit or probit specification, and an additional analysis of data from Brown and Harris [Social Origins of Depression: A Study of Psychiatric Disorder in Women. The Free Press, New York, 1978] supports these arguments. Thus, the study concludes that the strain hypothesis of social support is more consistent with the available data. PMID- 8356484 TI - Health care behavior on Nicaragua's Atlantic Coast. AB - Survey methods are used to investigate health behavior in five communities on Nicaragua's Atlantic Coast. Eighteen health behaviors classified as 'biomedical' or 'traditional' are analyzed according to the ethnicity and educational level of the respondent. Household location (urban vs rural) and material wealth are also analyzed as predictors of health care behavior. Traditional behaviors are found to vary considerably among the six ethnic groups and among the various socioeconomic groupings. Biomedical behaviors are not found to be clearly related to ethnicity, wealth, or education. PMID- 8356483 TI - Health care financing for the elderly in Japan. AB - This paper examines the financing of elderly health care in Japan for medical institutions, nursing homes, and at home. The analysis demonstrates that the conventional figures for elderly health expenditures in Japan systematically underestimate the real costs by excluding the costs of uninsured services, nursing homes, and home health care. The paper estimates these costs and shows that they add about 10% to the conventional figure for elderly health care costs in Japan. This inquiry also shows how government policy for health care financing shaped distinctive Japanese patterns of elderly care provision. The financing system provided a hidden subsidy--through national health insurance coverage of long-term hospitalization--that encouraged high institutionalization rates of elderly in medical facilities. Public financing for long-term elderly hospitalization, however, has not been matched by government attention to quality of care, resulting in serious quality problems and reflecting a social trade-off between cost and quality. Also, until recently the financing system rarely reimbursed home health care, thereby creating strong disincentives to the development of formal home health care services. This analysis has important implications for reforms now being considered by the Japanese government in the financing and provision of health care for the elderly, especially the limitations of relying on reimbursement price policy. The reforms could have unintended negative consequences for equity, efficiency, and quality of care. PMID- 8356485 TI - User fees plus quality equals improved access to health care: results of a field experiment in Cameroon. AB - Since the Bamako Initiative was launched in 1988, many African countries have embarked on comprehensive primary health care programs relying, at least partially, on revenues generated through user fees to revitalize health care delivery systems. Although these programs contain two critical components, user fees and improved quality, policy debates have tended to focus on the former and disregarded the latter. The purpose of this study is to provide a net assessment of these two components by testing how user fees and improved quality affect health facility utilization among the overall population and specifically among the poorest people. A "pretest-posttest controlled" experiment was conducted in five public health facilities in the Adamaoua province of Cameroon. Three health centers which were to introduce a user fee and quality improvement (i.e. reliable drug supply) policy were selected as "treatment" centers and two comparable facilities not yet phased into this policy were selected as "controls". Two rounds of household surveys were conducted (each to 800 households in 25 villages surrounding the five study sites) to measure the percentage of ill people seeking care at the health center before and after the implementation of the policy. The experiment was tightly controlled by conducting monthly observations at each study site. Results indicate that the probability of using the health center increased significantly for people in the "treatment" areas compared to those in the "control" areas. Travel and time costs involved in seeking alternative sources of care are high; when good quality drugs became available at the local health center, the fee charged for care and treatment represented an effective reduction in the price of care and thus utilization rose. Moreover, contrary to previous studies which have found that the poorest quintile is most hurt by user fees, this study found that probability of the poorest quintile seeking care increases at a rate proportionately greater than the rest of the population. Since the poor are most responsive to price changes, they appear to be benefitting from local availability of drugs more than others. PMID- 8356487 TI - The general practitioner's use of time: is it influenced by the remuneration system? AB - The practice pattern of 116 general practitioners in 60 rural municipalities in Northern Norway was studied with respect to length of consultation, the weekly number of consultations and the proportion of return visits. The average length of consultation was 14 mins, and only slightly lower for fee-for-service (FFS) doctors (13.7) than for salaried ones (14.8). The weekly average number of surgery consultations was higher for FFS doctors than for the salaried (63 vs 49), but the weekly number of hours spent consulting and the proportion of return visits were about the same. Further, the characteristics of the health care system (doctor density and doctor turnover) were associated with variations in the doctors' use of time. The most consistent effects, even if weak, were the age and sex of the patients. The strongest effects on the length of consultation were referrals and various medical procedures. This suggests that in this instance the medical condition at hand would appear to have a greater influence on the doctors' use of time than either the remuneration system or other characteristics of the health care system. Although the association between the doctors' use of time and the type of remuneration was weak, the study indicates that the type of remuneration does matter. Consequently, financial incentives can be used to influence the practice pattern of GPs. PMID- 8356486 TI - Ways of coping with chronic fatigue syndrome: development of an illness management questionnaire. AB - Chronic fatigue syndrome (CFS) is a disorder of uncertain aetiology, and there is uncertainty also about the appropriate way in which patients should manage the illness. An illness management questionnaire (IMQ) was designed to assess coping in CFS. This was completed by 207 patients, in parallel with the COPE scales (a general measure of coping that can be applied situationally), and measures of functional impairment, anxiety and depression. The IMQ yielded four factors: maintaining activity, accommodating to the illness, focusing on symptoms and information-seeking. Scales based upon these factors together predicted 26, 27 and 22% of the variance in functional impairment, anxiety and depression, respectively, and each scale had significant relationships with relevant scales of the COPE, supporting the interpretation of the factors. It is suggested that the IMQ may be employed to relate ways of coping to outcomes in CFS, and to assess coping as a mediator of change in cognitive-behavioural interventions. PMID- 8356489 TI - Assessment of trends in geographical inequalities in infant mortality. AB - After discussing the comparative effectiveness of different measures of dispersion used as indices of inequality, the Weighted Coefficient of Variation is proposed as an appropriate indicator of geographical inequality attending infant death. Furthermore, this paper proposes a methodology based on simple linear regression to be employed for the purposes of assessing the percentage of the observed change in said inequality over any given period, as is required by the terms of Target 1 of the WHO policy document "Health for All by the Year 2000". To this end, trends in Infant, Neonatal, Postneonatal and Perinatal Mortality in Spain for the period 1975-1986 have been analysed. For the 12 years examined, the Average Spanish Rate for these four indicators fell by over 50%. We observed a statistically significant decrease (34.8%) in geographical inequalities in the case of Postneonatal Mortality. However for the same period, geographical inequalities in Perinatal Mortality showed an important and significant rise (79.33%). It is suggested that, where Spain is concerned, it is Perinatal Mortality which should be assigned priority status for monitoring purposes. A plan of action should be drawn up, duly targeted at reducing geographical inequalities in health services, in the mother-and-child care sector above all. PMID- 8356488 TI - Sexual behaviors relevant to HIV transmission in a rural African population. How much can a KAP survey tell us? AB - KAP surveys have been proposed as a means to gather quantitative information on AIDS-related sexual behaviors, but the validity of survey results has not been tested. The validity of data gathered during a KAP survey in a rural district in Northern Uganda (N = 1486) was examined analyzing expected behavioral patterns, agreement of partner reports, and concordance of number of sexual contacts across gender. Patterns of sexual behavior and age trends are as expected. More men (50%) than women (18.5%) reported premarital sex. The likelihood of sexual intercourse before marriage increases with age at first marriage and with education. Women marry 5 years earlier than men, and the number of marriages increases with age. Peak incidence of casual sex occurs before age 25. The male/female ratio of casual sex is 4, as compared to about 3 in other African surveys. Single men are 2.5 times more likely to engage in casual sex than married males. Agreement of partner reports was examined for 392 couples selected by chance. 86% of the couples agreed on being polygamous or monogamous. On average men reported 1.3 (SD = 0.7) wives as compared to women reporting 1.5 (SD = 0.89) wives (P < 0.001). 16.8% of women declared more, and 2.8% less cowives than their husband (r = 0.65). Self-reports on frequency of sexual intercourse in the past month were examined for 256 monogamous couples. Mean frequencies differ (5.24 +/- 5.1 for men, 4.43 +/- 4.7 for women, P < 0.001). 42.8% of couples are in agreement within +/- 1 unit (r = 0.44). The total number of extra-marital and marital sex acts, as well as the total number of partners reported by each gender are similar. There is, however, a striking gender difference in reporting of casual partners in the past year. Data were found to be accurate at the aggregate level. However, accuracy of reporting at the individual level was found to be low. The gender difference in reporting of casual partners may be due to female underreporting, to not having captured prostitutes or to a different perception of the meaning of casual partnership. All KAP surveys should include a validity analysis, so as to provide a sense of the accuracy of the surveys and allow for comparison of the quality of different KAP surveys. There is an urgent need for a standardized approach to validating the findings from AIDS-related KAP surveys. Some of the indirect methods described here could be relevant for further use. PMID- 8356490 TI - Motorcycling safety research: a review of the social and behavioral literature. AB - The literature on motorcycling safety research is reviewed, and it is argued that there have been two main periods. The first, spanning the 1970's, was based on accident analysis, and the main objective was to identify and control factors that contribute to the severity of motorcycling accidents. The main concerns were to reduce head and brain injuries through safety helmets, to reduce multi-vehicle collisions through daytime use of headlamps, and to reduce drink-riding. The second period, the 1980's shifted the emphasis of research to what might be called 'riding analysis'--that is, analysis of the process of motorcycle riding. Particular attention was paid to skills testing, training evaluation and perceived risk. Now, in the early 1990's, a third period is developing, in which the rider is seen as 'active agent'. The theoretical basis of the new research has come from the models of social psychology, and the main concern is to use riders' beliefs and attitudes about safe riding to predict their behaviour on the roads and so their accident involvement. The three periods of research are reviewed in turn, and the paper concludes with an outline of the key research issues that remain to be addressed. PMID- 8356491 TI - Concurrent utilization of chiropractic, prescription medicines, nonprescription medicines and alternative health care. AB - This study examines the use of chiropractic, prescription medicines, nonprescription medicines and alternative health care for two independent samples representative of the population of Edmonton, Alberta, Canada in 1979 (n = 439) and again in 1988 (n = 464). While the usage of prescription medicines was unchanged from 1979 to 1988, utilization of nonprescription medicines, chiropractic and alternative health care increased. Users of chiropractic tended to be concurrent users of the conventional health care system, although they were also more likely to utilize alternative health care. This study shows that Edmontonians tend to select their health care concurrently from various health care modalities including both prescription and nonprescription medicines and conventional and alternative health care. PMID- 8356492 TI - A fifteen year experience with open drainage for infected pancreatic necrosis. AB - Advances in the understanding of the pathophysiologic factors of acute pancreatitis, combined with several recent technologic breakthroughs, have led to the establishment of infected pancreatic necrosis as the most common, the most severe and the most lethal of the infectious complications of acute pancreatitis. In this report, a single institutional experience in the surgical management of infected pancreatic necrosis during a 15 year period is chronicled. Using open drainage with scheduled abdominal re-explorations, the overall mortality rate was 15 percent in 71 consecutive patients with infected pancreatic necrosis. In the most recent 25 instances, sequential re-explorations were performed until retroperitoneal granulation occurred, at which time the abdomen was closed over lesser sac lavage catheters. Compared with the original 46 patients permitted to heal entirely by secondary intention, patients undergoing delayed secondary closure and lavage had a significant decrease during the hospitalization period (48.8 versus 30.1 days; p < 0.05), without a significant change in the mortality rate. In the most recent patients, dynamic pancreatography and fine needle aspiration bacteriologic factors were accurate in the preoperative prediction of pancreatic necrosis and microbial infection in 95 and 97 percent of the patients, respectively. Preoperative endoscopic retrograde cholangiopancreatography demonstrated leakage of contrast material from necrotic pancreatic ducts in seven of eight patients, while postoperative pancreatograms revealed abrupt truncation or other abnormalities in 11 of 13 patients. These observations establish that necrotizing pancreatitis involves pancreatic parenchyma as well as peripancreatic adipose tissue. Open drainage with contingent secondary closure and high volume lavage deserves a place in the management of patients with extensive infected pancreatic necrosis. PMID- 8356493 TI - Surgical management of gastroduodenal ulcer associated with hiatal hernia. AB - The problem of surgical management of gastric and duodenal ulcers associated with the hiatal esophageal hernias is reported. The authors have summed up the results of simultaneous surgical treatment of 97 patients. Good follow-up results were obtained in 69.2 percent of the patients, satisfactory in 26.9 percent and unsatisfactory in 3.9 percent of the patients. Of the 28 patients with reflux esophagitis who had previously undergone gastric resection, it was noted that nonresection of the associated hiatal hernia during the primary operation for ulcer disease decreased the effect of surgical treatment. A new method of surgical management of reflux esophagitis of the resected stomach is presented. The authors conclude that simultaneous operation for gastroduodenal ulcers associated with hiatal hernia is a promising area of surgical treatment and ensures high medical, social and economic efficiency. PMID- 8356494 TI - The significance of a positive test of morphine cholescintigraphy in hospitalized patients. AB - Morphine-augmented radionuclide cholescintigraphy (MC) is a useful adjunctive diagnostic tool for the identification of acute cholecystitis (AC) in patients who are hospitalized and critically ill with occult sepsis. The results of previous studies have demonstrated a reduction in false-positive rates, that is, nonvisualization, from 40 percent with standard radionuclide cholescintigraphy to 5 percent with MC in these high-risk patient groups, with an overall accuracy of 92 percent. This study was performed to determine the significance of a positive test result from MC in patients with occult sepsis. We reviewed the records of all 20 patients at high risk in whom MC was positive during the 35-month period ending 31 May 1992. AC was confirmed by laparotomy in all 16 patients who underwent surgical treatment. There were two patients who recovered with antibiotic therapy alone (considered false-positives) and two additional patients who died without operation or a confirmed diagnosis of AC (excluded from analysis). Thus, in this series, MC was associated with a positive predictive value of 0.89, confirming that it is a valuable adjunct in establishing the diagnosis of AC in patients who are seriously ill and hospitalized with occult sepsis. PMID- 8356495 TI - Results of a prospective study with comparison of clinical, endosonographic, computed tomography, magnetic resonance imaging and pathologic staging of advanced gynecologic carcinoma and recurrence. AB - Between January 1988 and April 1991, 57 patients with advanced gynecologic carcinoma were preoperatively evaluated by gynecologic examination and endosonography (ESG) using general anesthesia. Abdominopelvic computed tomography (CT) was performed in 49 patients and magnetic resonance imaging (MRI) in 21 patients. There were 34 primary tumors and 23 instances of recurrence. Causes of gynecologic carcinoma were 38 carcinomas of the cervix uteri (26 primary and 12 recurrences), eight carcinomas of the ovary (four primary and four recurrences), three recurrences of carcinoma of the endometrium, five sarcomas of the uterus (one primary and four recurrences) and three primary carcinomas of the vagina. All of the patients were operated upon. This perspective study compares the data from clinical and imaging examinations to the data obtained from histologic examination of surgical sections. According to anterior or posterior tumor extension, the accuracy of clinical evaluation and preoperative imaging were studied for the posterior vesical wall and the vesicovaginal septum and the anterior rectal wall and the rectovaginal septum. Histologic examination revealed vesical involvement in 17 patients and of the involvement of vesicovaginal septum in 21 patients. The accuracy of the clinical examination, ESG, cystoscopy, CT and MRI was 83, 88, 87, 75 and 81 percent, respectively, for vesical extension. Cystoscopy was not taken into account for evaluation of extension to the vesicovaginal septum--accuracy was 80, 90, 67 and 86 percent for clinical examination, ESG, CT and MRI. Histologic examination showed involvement in the rectum in 14 patients and involvement in the rectovaginal septum in 19 patients. Rectoscopy was performed 13 times. The accuracy of clinical examination, ESG, CT and MRI was 91, 98, 89 and 71 percent, respectively, for extension to the anterior rectal wall. Rectoscopy was not taken into account for evaluation of extension to the rectovaginal septum--accuracy was 80, 96, 75 and 57 percent for clinical examination, ESG, CT and MRI. Endosonography would seem to be useful to complete examinations for regional extension of advanced gynecologic carcinomas. Its accuracy is superior to that of other examinations. Because it is performed using general anesthesia, there is no discomfort for the patient during this low cost procedure. PMID- 8356496 TI - Identifying the low-risk patient with penetrating colonic injury for selective use of primary repair. AB - As the mortality rate for penetrating colonic injuries approaches zero, emphasis has shifted toward reducing associated morbidity. This study was done to identify patients at low risk for colon-related extensive morbidity after primary repair of a penetrating colonic injury. The records of 100 consecutive patients admitted to the District of Columbia General Hospital (DCGH) between 1984 to 1990, surviving more than 24 hours after full-thickness penetrating colonic injuries, were retrospectively reviewed. Data collection included mechanism, management and anatomic location of the colonic injury. Severity of injury was evaluated by the Trauma Score (TS), Penetrating Abdominal Trauma Index (PATI), Flint Colon Injury Score (FCIS), time in the operating room, blood transfused during the first 24 hours and presence of preoperative shock (systolic blood pressure less than 90 millimeters of mercury). Mechanism of injury included 97 gunshot wounds and three stab wounds. Fifty-seven patients had primary repair (17 having resection and anastomosis) and 43 had colostomy. The anatomic location of injury was right colon in 37, transverse colon in 27, left colon in 35 and multiple sites (two) in one patient. In this series, only two patients had colon-related extensive morbidity--a parastomal hernia and wound dehiscence, both requiring operative intervention. There were no instances of intraperitoneal abscess formation. One patient died from overwhelming pneumonia after segmental resection of the colon with primary anastomosis. The literature reports a 12 to 42 percent colon-related morbidity rate in patients sustaining penetrating colonic injuries. This series from DCGH represents the lowest colon-related extensive morbidity and mortality rates reported to date in any substantial series of penetrating abdominal trauma. We attribute the 2 percent extensive morbidity rate to high TS (mean of 15.7), low PATI (mean of 24.2), low FCIS (mean of 1.9) and few associated intra abdominal injuries (59 percent of patients with less than two). We have identified a group of patients with full-thickness penetrating injuries to the colon, few associated intra-abdominal injuries, high TS, low PATI and low FCIS who can be managed safely and judiciously by primary repair without undue morbidity and mortality. PMID- 8356497 TI - Surgical scar endometrioma. AB - Relatively few instances of surgical scar endometrioma have been reported. Herein we review 24 patients treated for this condition at the institutions at which we work between 1972 and 1992. The age of the patients ranged from 17 to 47 years, with an average age of 31.7 years. Surgical scar endometriomas occurred after operations including cesarean section (19 patients), appendectomy (two patients), episiotomy (two patients) and hysterectomy (one patient). The interval between prior surgical treatment and the onset of symptoms ranged from one to 20 years, with an average of 4.8 years. All patients were treated by wide excision. Seventeen of 24 patients were available for follow-up evaluation. The interval between excision and follow-up evaluation ranged from 1.2 to 14.0 years, with an average of 6.4 years. None of the patients had recurrence of surgical scar endometrioma. Patients with the classic presentation of a painful surgical scar mass that increases in size or tenderness during menstruation need no further evaluation of the lesion before excision. Ultrasonographic examination and fine needle aspiration biopsy should be used preoperatively in women who have a constantly painful or asymptomatic mass in a surgical scar. Because medical management yields poor results, wide excision of surgical scar endometriomas is the treatment of choice. PMID- 8356499 TI - A randomized comparison of Verres needle and direct trocar insertion for laparoscopy. AB - Two hundred and fifty-two women scheduled to undergo laparoscopy were randomly assigned to a Verres needle or direct insertion group. The groups were similar with respect to incidence of obesity, prior surgical treatment, indication for operation and level of training of the surgeon performing the procedure. There were no major complications associated with either technique. Minor complications (preperitoneal insufflation, failed entry or more than three attempts necessary to enter the peritoneal cavity with the trocar) were significantly more frequent (p < 0.05) in the Verres needle technique group. One hundred and thirteen of these patients underwent sterilization procedures. The mean times for performance of the laparoscopic procedure using the direct insertion and Verres needle techniques was 15.3 and 19.6 minutes, respectively. The time saved using the direct insertion technique is explained by a significant (p < 0.01) reduction in the mean laparoscope insertion time, which was 2.2 minutes and 5.9 minutes for the direct insertion and Verres needle techniques, respectively. We prefer the direct insertion technique for trocar placement because it has fewer minor complications and requires less operating time. PMID- 8356498 TI - Superior mesenteric arteriovenous fistula in vascularized whole organ pancreatic allografts. AB - Despite improved results in vascularized pancreatic transplantation, the incidence of technical complications continues to be high. Vascular complications are an important source of morbidity. Previously undescribed is the occurrence of an arteriovenous fistula (AVF) in the transplanted mesenteric bundle. We have identified this unusual complication in three of 90 consecutive recipients of pancreatic transplant. The first patient presented with severe and protracted endocrine insufficiency, which was effectively reversed by direct surgical ligation of the AVF. The second patient presented with hematuria, which likewise, resolved with correction of the AVF. The third instance was diagnosed immediately after transplant and was successfully corrected by direct surgical ligation. The operative approach with establishment of proximal vascular control differed in each instance. Clinical presentation was variable and diagnosis was suggested by physical examination, duplex ultrasonography and radionuclide perfusion scanning. Arteriography was confirmatory. Mesenteric AVF can be easily identified and corrected at the time of reoperation without compromising allograft function. PMID- 8356501 TI - Appendectomy incidental to cholecystectomy among elderly Medicare beneficiaries. AB - To assess the risks of adverse outcomes after appendectomy incidental to cholecystectomy among elderly Medicare beneficiaries, 8,936 persons undergoing cholecystectomy with incidental appendectomy and 44,461 persons undergoing cholecystectomy without incidental appendectomy were studied. Controlling for age, race, gender and co-morbidity status, the risk for wound infection in persons with incidental appendectomy was 83 percent higher than in persons without incidental appendectomy (95 percent confidence interval, 1.53 to 2.18). The risks for having other adverse outcomes, including other infections, extensive intrahospital complications and mortality rate at 30 days, were also higher for the former group, although these differences were not statistically significant. In addition, the demographic characteristics and health status of persons undergoing cholecystectomy with incidental appendectomy with persons undergoing cholecystectomy only were compared. Males, persons of younger ages, of white race or with no co-morbid conditions, were significantly more likely to undergo cholecystectomy with incidental appendectomy. Variables to control for differences in the demographic characteristics and health status between persons receiving and not receiving incidental appendectomy were included in the regression models for adverse outcomes. However, these models may not completely control for differences between the two groups. As a result, the actual relationship between incidental appendectomy and adverse outcomes may be underestimated. The preventive effect of incidental appendectomy on morbidity and mortality rates from future instances of appendicitis was assessed by determining the remaining lifetime risk for acute appendicitis. For persons 65 to 69 years of age, 115 incidental appendectomies would be required to prevent one future instance of appendicitis and 4,472 incidental appendectomies would be needed to prevent a single future death from acute appendicitis. Because incidental appendectomy increases the risk for wound infection among persons undergoing cholecystectomy and because the lifetime risk for acute appendicitis is relatively low for persons of this age group, surgeons should carefully consider the risks and benefits of incidental appendectomy in the elderly. PMID- 8356500 TI - Optimal outcome after tibial arterial bypass. AB - To evaluate factors for the optimal outcome after tibial arterial bypass for lower extremity ischemia, we analyzed our experience with 1,359 such bypasses during the last ten years. There were 869 males and 490 females, of whom 739 patients (54 percent) had diabetes. The average age was 68 years. One thousand and twenty-four bypasses were performed using the atraumatic valve incision in situ technique, 281 bypasses using free vein grafts and 54 bypasses with synthetic materials. These bypasses were taken to the anterior tibial (312 patients), posterior tibial (341 patients), peroneal (520 patients) and dorsalis pedis arteries (125 patients). Inflow arteries included external iliac (two patients), common (435 patients), superficial (472 patients) and profunda femoris arteries (259 patients). In certain instances, popliteal and tibial arteries were used for inflow (short bypasses). Limb salvage was the significant indication (95 percent). The overall cumulative primary patency rate at five years was 68 percent and secondary patency was 76 percent. In situ bypasses had the best secondary patency rate of 80 percent at five years followed by free vein grafts of 70 percent and synthetic bypasses of 33 percent. The choice of inflow or outflow arteries did not influence the patency rate in any category. The overall limb salvage rate was 94 percent at five years. Short bypasses using free vein grafts had a similar patency to long free vein graft but lower patency than long in situ bypasses. These data demonstrate that bypasses to tibial arteries, using autogenous vein for ischemia of the lower extremity and limb salvage, have long term durability. In situ bypass with a complete saphenous vein is the best conduit for such reconstructions. We suggest that tibial arterial bypass should be strongly considered in all instances for limb salvage when autogenous vein is available before resorting to primary amputation. PMID- 8356502 TI - A direct approach to the left and middle hepatic veins during left-sided hepatectomy. AB - A direct surgical approach to the MHV during left-sided hepatectomy is anatomically feasible. The procedure should be applied with appropriate safety measures. Prior verification of the precise anatomic relationship of the hepatic veins is necessary and the MHV should be isolated and secured by the described stepwise technique. PMID- 8356503 TI - Four steps to local anesthesia for endarterectomy of the carotid artery. PMID- 8356504 TI - Integrins, adhesion molecules and surgical research. AB - Integrins and adhesion molecules are a group of closely related glycoproteins expressed by a wide variety of cells. In vitro experiments have shown these families of cell surface receptors to be essential to the interactions between the cytoskeleton and the extracellular matrix. Although the designations of families of integrins and adhesion molecules is complex, this review attempts to present an organization in which the result is to provide surgeons with an understanding of their structure and function. This is particularly important because integrins and adhesion molecules have a critical role in such diverse processes as embryogenesis, inflammation, wound healing, thrombosis, transplantation and oncogenic transformation. It is, therefore, highly probable that they will be critical to future advances in surgical research and ultimately in surgical practice. It should be remembered that this area of investigation is so dynamic that the interval involved in publication of this article will in itself be characterized by a plethora of publications in the basic science and surgical literature, which warrants careful attention. PMID- 8356505 TI - [Questions and aspects of radiotherapy of adult patients with localized supradiaphragmatic stage (CS I/II) Hodgkin's disease. 1. Questions and aspects on indications for primary and adjuvant radiotherapy]. AB - Important studies of the therapy in patients with early stages of Hodgkin's disease aim at reducing the long-term risks, yet maintaining the high cure rate. Several prospective studies and two large meta-analyses did not observe a significant difference of the ten- or 15-year survival rate after radiotherapy or combined radio- and chemotherapy in the total group of patients with CS I/II A Hodgkin's disease, not withstanding a significant reduction of the recurrence risk after combined therapy. There is some evidence but no proof, that certain subgroups of patients with early stage, have a higher survival after combined therapy compared to that after radiotherapy alone. Most studies of therapy in Hodgkin's disease have a statistical power much too low, in order to demonstrate significant differences of the survival rate in the order of 10 to 15%. Randomized studies of chemo- versus radiotherapy in patients with PS I/II A and some PS III A have shown conflicting results. Patients with supradiaphragmatic Hodgkin's disease and CS I/II can be subdivided according to the recurrence risk after primary radiotherapy in the following subgroups: 1. Patients with a very low or a low recurrence risk of approximately 10 to 20%: patients less than 40 years old and CS I/II A NS/LP with less than three involved regions and no bulky mediastinal mass and an ESR below 30 mm. If there is only unilateral suprahyoidal lymph node involvement, primary radiotherapy of the involved region or a mini mantle or a mantle field is acceptable and achieves a recurrence free survival of 90% or higher. If there is only non bulky mediastinal involvement, mantle field radiotherapy is acceptable and achieves a recurrence-free survival of at least 90%. In the other patients, primary irradiation of an extended mantle field without a staging laparotomy is an acceptable primary treatment, achieving a recurrence-free survival rate of approximately 80%. Another option is a staging laparotomy with splenectomy and a mantle radiotherapy for PS I/II. Few groups prefer primary chemotherapy alone or some type of a reduced chemotherapy with lesser toxicity combined with localized radiotherapy and long-term observations of a larger group of patients after the last type of treatment have to confirm the excellent early results. 2. Patients with an intermediate recurrence risk of approximately 20 to 40%: patients, who do not belong to group one or group 3.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8356506 TI - Prognostic factor of radiotherapy for squamous cell carcinoma of oropharynx without clinically positive nodes. AB - Local control rates of oropharynx carcinoma treated with radiation alone were reported as 40 to 71%. We investigate the factors which affect the local control rate for oropharynx carcinoma. From 1967 through 1982, 62 cases of squamous cell carcinoma of oropharynx without positive neck nodes were treated with external radiation at the Department of Radiology, Osaka University Hospital. Five-year actuarial survival rates of T1, T2, T3 and T4 cases were 53%, 63%, 47% and 0%, respectively. Five-year local control rates of T1, T2, T3 and T4 cases were 51%, 46%, 34% and 0%, respectively. In 52 cases treated with a total dose of 60 Gy or more, tumor response could be evaluated at the dose level of 40 and 60 Gy. The local control rates of tumors which disappeared and persisted at 40 Gy were 88% (7/8) and 39% (17/44), respectively (p < 0.05). Of 44 cases which persisted at 40 Gy, the local control rates of tumors which disappeared and persisted at 60 Gy were 48% (11/23) and 29% (6/21), respectively (p > 0.30). Evaluation of tumor response at 40 Gy was an important indicator of local control for N0 oropharynx carcinoma. PMID- 8356507 TI - High-dose-rate remote afterloading intestinal radiotherapy employing the template technique for recurrent cancer in the pelvic area. AB - Between December 1991 and August 1992, five patients with recurrent cancer in the pelvic area (four gynecological cancers and one rectal cancer) were treated at Osaka University Hospital with a remote afterloading interstitial implantation employing the template technique. External irradiation (40 to 50 Gy) was performed in four cases one to four weeks before brachytherapy. Interstitial high dose-rate brachytherapy (24 to 40 Gy/four to eight fractions/two to four days) was performed twice a day. Three of the five patients achieved complete local tumor control. The remaining two patients obtained symptom relief. There were no complications serious enough to need surgical treatment. Moreover, this procedure is well tolerated and therefore an effective modality for elderly and frail patients. PMID- 8356508 TI - A method for improving the output dose rate protocols for cobalt machines. AB - A method of correcting the output dose rate of the radiotherapeutic cobald units is presented. This method links measurements values with the decay formula for increasing the accuracy of output dose rate determining. The least squares method has been applied to mathematical processing of the data. Results were discussed on the record of output dose rate which had been measured since 1969. PMID- 8356509 TI - CT assisted computation of collimator angle and importance of off-axis planning of inclined lesions. AB - In the radiation treatment of inclined lesions the longitudinal axis of beam should be always parallel to the longitudinal axis of lesion in the treatment plane. Hence the choice of correct collimator angle is of prime importance in the oblique field off-axis treatment planning of inclined lesions. In this paper a graphical method is discussed to determine the collimator angles from the CT scans taken at different off-axis planes. A phantom was constructed which can simulate conditions like inclined lesion in the patient and CT scans were taken at different levels. The collimator angles estimated from CT scans are found to match with the collimator angles obtained from simulator within +/- 1 degree for various gantry angles. The method is applied to plan a case of cancer of the oesophagus (upper third), which is a typical example of inclined lesion. PMID- 8356510 TI - [Electron microscopic studies of the effect of x-rays and L-3,4 dihydroxyphenylalanine (L-Dopa)--alone and in combination-- on Harding-Passey melanoma cells in monolayer cell culture]. AB - Monolayer cultures of Harding-Passey melanoma cells in exponential growth phase were exposed to 8 or 16 Gy by X-ray treatment. The 8 Gy treated cells revealed little ultrastructural changes, while the 16 Gy exposed cells showed increased damage as segregates, swollen mitochondria and vacuoles. Sole treatment with L 3,4-dihydroxyphenylalanine (2 x 10(-4) M L-Dopa) resulted in insignificant electronmicroscopically tangible cell alterations. Combined treatment--starting with 8 Gy irradiation followed by a six-day incubation in the presence of 2 x 10( 4) M L-Dopa--revealed more pronounced cell damage with final cell disintegration; the cytoplasm contained an increased number of vacuoles and segregates, a strongly decreased endoplasmic reticulum as well as swollen mitochondria and less pinocytosis vesicles; the cell surface showed less microvilli. Melanin containing organelles increased after the combination treatment. The growth inhibitory and cell destructive influence of L-Dopa on X-ray pretreated melanogenic melanoma cells was explained with the formation of cytotoxic oxidation products of L-Dopa. PMID- 8356511 TI - Individualization of hernia repair: a new era. PMID- 8356512 TI - Liver transplant in complete situs inversus: a case report. AB - BACKGROUND: Several technical solutions have been proposed for patients with situs inversus (SI) needing liver transplantation. This report describes the hepatic replacement in a patient with complete SI with dextrocardia. In the only other reported patient with complete SI the donor right lobe was placed over the vertebral column and the stomach to align the donor cava with that of the recipient. METHODS: A 45-year-old woman with complete SI, suffering from Laennec's cirrhosis with frequent upper gastrointestinal hemorrhages, underwent transplantation in June 1991. The recipient weighed 48.2 kilograms and was 155 centimeters tall. The donor weighed 77.3 kilograms and was 188 centimeters tall. The weight of the native liver was 1934 grams, and the donor liver weighed 1595 grams. RESULTS: At hepatectomy of the native liver an intact vena cava was left behind. Donor liver was rotated 90 degrees to the left, making the donor left lobe point into the left iliac fossa and the donor right lobe fall into the recipient hepatic fossa. Donor infrahepatic vena cava was sewn end-to-side to the recipient vena cava. Suprahepatic vena cava was oversewn. Donor and recipient hila were well aligned, allowing a standard arterial reconstruction and a choledocholedochostomy. Patient's recovery was uneventful with no problems during the following 6 months. CONCLUSIONS: The proposed technique for a patient with complete SI and dextrocardia offers several advantages: no need to downsize the donor in comparison with the recipient; no need for cutdown of the liver; no risk of kinking of the venous outflow; hepatic hila are aligned; and it allows for a standard arterial and biliary reconstruction. We recommend this technique as a procedure of choice for patients with SI and an intact vena cava. PMID- 8356513 TI - Metachronous bilateral nonfunctional intercarotid paraganglioma (carotid body tumor) and functional retroperitoneal paraganglioma: report of a case and review of the literature. AB - BACKGROUND: The occurrence of an intercarotid paraganglioma and a paraganglioma in an anatomic distribution away from the head and neck in the same patient is rare. We have treated a patient with this combination of tumors and report this unusual case with the purpose of reviewing the paraganglion system. We endeavor to clarify the confusion that exists by use of the terms chemodectoma, glomus tumors, nonchromaffin paragangliomas, and pheochromocytoma and to present a rational nomenclature based on their ontogeny. METHODS: A computer-generated list of articles on this subject was obtained, and all articles relative to this rare combination of tumors were reviewed. RESULTS: We found 31 other cases. Functional intercarotid paragangliomas are extremely rare, with only five cases having been reported. CONCLUSIONS: All hypertensive patients who are found to have an intercarotid paraganglioma should be investigated for a functional tumor. Family members should also be made aware of their probabilities of having these tumors because a familial trend has been documented in certain cases. PMID- 8356514 TI - Closure of complex abdominal wall defects with bilateral rectus femoris flaps with fascial extensions. AB - Large full-thickness abdominal wall defects present a difficult reconstructive problem. Synthetic mesh has significant drawbacks and should be used only as a temporizing measure. Ideally abdominal wall defects should be resurfaced with well-vascularized autologous fascia and skin. A variety of myofascial, myocutaneous, and myofasciocutaneous flaps have been described. This report describes two cases of near-total abdominal wall reconstruction using bilateral rectus femoris myocutaneous flaps with fasciocutaneous extensions of superficial thigh fascia and skin. In both cases the rectus femoris flaps and fascial extensions healed, and the patients went on to full recovery. In one patient the skin over the fascial extension did not survive and had to be debrided and the underlying vascularized fascia resurfaced with a skin graft. The extended rectus femoris flap is a reliable and versatile flap that leaves negligible functional deficits. The fascial extensions are reliable and well perfused and should be included in the reconstruction of larger abdominal wall defects. The skin overlying the fascial extensions is less reliable, and selective use is recommended. PMID- 8356515 TI - Reflex sympathetic dystrophy after modified radical mastectomy: a case report. AB - Despite the long history of descriptions of reflex sympathetic dystrophy (RSD), much confusion remains regarding its pathogenesis, diagnosis, and treatment. It most commonly occurs after trauma and is more frequent in women, white persons, and the elderly. The first case of RSD after mastectomy is reported and the proposed pathophysiology and management of RSD are reviewed. PMID- 8356517 TI - Primary adenocarcinoma arising in an ileostomy. AB - Two cases are added to the world literature of patients in whom an adenocarcinoma developed at the ileostomy site after total proctocolectomy for ulcerative colitis. Fourteen additional cases have been reported in the world literature; of these, 12 cases have been in patients with ulcerative colitis, and four cases have been in patients with familial adenomatous polyposis. Adenocarcinoma of an ileostomy is not common. However, in the analysis of the reported cases, patients with long-standing ileostomies appear to be at a greater risk. With an aging ileostomy population, an increase in the number of cases may be seen. Three hypotheses are discussed as potential causative pathways to this entity. Continued analysis of these cases may yield information on the pathophysiology involved. PMID- 8356516 TI - Implant metastasis of gallbladder carcinoma in situ in a cholecystectomy scar: a case report. AB - A subcutaneous mass within the scar left by cholecystectomy with common bile duct exploration and T-tube drainage developed 6 years after surgery. Pathologic examination of this mass showed features of atypical villous hyperplasia, similar to that identified within the previously removed gallbladder, but with additional foci of carcinoma in situ. Since excision of the mass, the patient has had persistent fluid collections requiring frequent aspiration. Cytologic analysis of the fluid has revealed tumor cells. The cause of this spread has been unclear. Few literature reports have identified biliary drainage techniques as a source for metastatic seeding. The malignant or metastatic potential of severe dysplasia or carcinoma in situ of the gallbladder associated with T-tube drainage and implantation in the drainage tract is previously unreported. PMID- 8356518 TI - Long bone fractures and pulmonary dysfunction. PMID- 8356519 TI - Basis for beneficial effects of partial portal decompression. PMID- 8356520 TI - Laparoscopic cholecystectomy in neoplasms of the gallbladder. PMID- 8356521 TI - Laparoscopic surgery and tumor seeding. PMID- 8356522 TI - "Tension-free" inguinal herniorrhaphy: a preliminary report on the "mesh plug" technique. AB - BACKGROUND: Since 1984 we have completed 3897 inguinal herniorrhaphies. This article compares our results with a conventional Cooper ligament repair versus the "mesh hernia plug" method. METHODS: From 1984 through 1988 we performed 2886 conventional Cooper ligament repairs. From 1989 through 1991 we completed 1011 mesh hernia plug repairs. RESULTS: Despite an acceptable recurrence rate (1.8%), we abandoned the Cooper ligament technique because of persistent difficulties with immediate postoperative pain, inability to reasonably resume day-to-day activities, delayed capacity regarding return to work, and four cases of femoral vein compression. Of the hernias repaired by the mesh plug method, the recurrence rate remains remarkably low (0.2%), and except for four superficial infections and three cases of urinary retention, no other significant complications have been reported. CONCLUSIONS: Compared with conventional sutured surgical techniques, a plug repair uses less overall dissection and ensures a "tension free" hernioplasty. We believe that the two factors of no tissue tension and decreased dissection are the most important reasons for greater patient comfort, rapid rehabilitation, decreased recurrence, and lessened overall complication rates with the mesh hernia plug technique. PMID- 8356523 TI - Ruptured abdominal aortic aneurysms: predictors for early complications and death. AB - BACKGROUND: Urgent operation for ruptured aneurysm is still associated with a high operative mortality rate. The purpose of the study was to determine the risk factors that truly influence early complications and death. METHODS: Between 1979 and 1991, 314 consecutive patients with a mean age of 69 years were treated surgically for a ruptured infrarenal abdominal aortic aneurysm. Twenty-two preoperative, perioperative, and intraoperative variables were subjected to a multivariate analysis to identify the independent predictors. RESULTS: Early death occurred in 92 (29%) of 340 patients. Significant primary predictors for early death were duration of cross-clamp (p < 0.0001), preoperative shock (p = 0.0005), suprarenal cross clamp (p = 0.002), and a history of coronary artery disease (CAD) (p = 0.004). The following postoperative complications were risk factors for death: myocardial failure (p < 0.0001), renal failure (p < 0.0001), sepsis (p = 0.01), and colon ischemia (p = 0.03). Predictors for postoperative myocardial insufficiency were a history of CAD (p < 0.0001), amount of intraoperative volume substitution (p < 0.0001), suprarenal cross clamp (p = 0.0007), and preoperative shock (p = 0.05). CONCLUSIONS: Preoperative and perioperative risk factors that result in fatal postoperative complications can be partially influenced by the surgeon. Short clamping time and infrarenal position of aortic clamp may lower overall early mortality rates. A history of CAD is a highly significant predictor for postoperative complications and early death. PMID- 8356524 TI - Effects of prostacyclin on spinal cord ischemia: an experimental study. AB - BACKGROUND: Paraplegia after thoracic aortic aneurysm has an incidence of 2.2% to 24%. This study was planned to show the beneficial effects of prostacyclin on spinal cord ischemia. METHODS: Twelve rabbits underwent 30 minutes of aortic occlusion. Six rabbits received prostacyclin, whereas the remaining rabbits did not. Prostacyclin administration was started with a rate of 5 ng/kg/min 5 minutes before aortic occlusion. This dosage was increased to 25 ng/kg/min during aortic occlusion. Prostacyclin administration after aortic occlusion was maintained for a period of 5 minutes. During this period, prostacyclin dosage was 5 ng/kg/min. RESULTS: One rabbit in the prostacyclin group and five rabbits in the control group were paraplegic. Arterial pressure proximal to the clamp was 65 +/- 7 mm Hg before aortic occlusion and 78 +/- 10 mm Hg during aortic occlusion in the control group and 68 +/- 12 mm Hg before aortic occlusion and 65 +/- 6 mm Hg during aortic occlusion in the prostacyclin group. Arterial pressure distal to the clamp was 11 +/- 4 mm Hg during aortic occlusion in the control group and 18 +/- 5 mm Hg during aortic occlusion in the prostacyclin group (p = 0.02). CONCLUSIONS: Intravenous prostacyclin reduced the neurologic injury caused by spinal cord ischemia and reperfusion after 30 minutes of aortic occlusion in the rabbit model. PMID- 8356525 TI - Extracorporeal venovenous recirculation for the treatment of hypothermia during elective aortic surgery: a phase I study. AB - BACKGROUND: Hypothermia caused by massive transfusion or prolonged exposure during operation is difficult to reverse and is associated with adverse side effects. This prospective, randomized study evaluated a technique using extracorporeal venovenous recirculation (EVR) through a roller pump-driven device with a commercial countercurrent heat exchanger used for treatment of hypothermia (temperature < 35.5 degrees C) occurring during elective aortic operation. METHODS: Patients undergoing aortic operation had routine prophylaxis against hypothermia including ventilator cascades, warming blankets, and low-velocity fluid warmers. When core temperature was less than 35.5 degrees C, patients were randomized to continue existing therapy (control, n = 7) or EVR (n = 8), performed through two large-bore venous lines. RESULTS: There were no differences in age, sex, weight, body surface area, Acute Physiology and Chronic Health Evaluation II score, fluid replacement, length of operation, blood lost or given, induction temperature, red blood cell or platelet structure, hemolysis, length of intensive care unit or hospital stay, complications, or mortality rates. EVR was associated with increased final core temperature (35.5 degrees +/- 0.8 degrees [EVR] vs 33.8 degrees +/- 0.9 degrees [control]; p < 0.005) and body heat content (-13.9 +/- 62.3 kcal [EVR] vs -118.2 +/- 62.2 kcal [control]; p < 0.01), with heat gained being proportional to flow rate. CONCLUSIONS: These data show that EVR provides a safe and effective method for the treatment of hypothermia. PMID- 8356526 TI - Contralateral disease progression after carotid endarterectomy. AB - BACKGROUND: We report the natural history of the carotid artery contralateral to the ipsilateral endarterectomized carotid artery. METHODS: The incidence of new symptoms and disease progression of the patient contralateral side after unilateral carotid endarterectomy (CE) was studied by clinical follow-up and serial duplex scanning in 127 patients. RESULTS: During a mean follow-up of 44 months, new hemispheric events occurred in nine (7%) and significant progression was recorded in 27 (21%) patients. In 97 patients with initial stenosis of less than 50% (group I), contralateral progression to greater than 50% was noted in 22% and new symptoms (one transient ischemic attack and one cerebrovascular accident) in 2% of patients; three patients underwent CE. In 30 patients with initial stenosis between 50% and 99% (group II), new symptoms (all transient ischemic attacks) occurred in seven (23%) (group II vs group I; p < 0.003) and nine underwent CE (group II vs group I; p < 0.001). Progression in 26 patients with 50% to 79% stenosis within group II to greater than 80% was noted in 19% of patients (difference not significant compared with group I). CONCLUSIONS: Overall, new symptoms occurred in 7% and significant contralateral disease progression in 21% of patients; subsequent CE was performed in 9.4% of patients. Initial presence of greater than 50% contralateral stenosis is a predictor of future hemispheric symptoms, which are likely to be transient ischemic attacks. New symptoms did not necessarily correlate with disease progression. Because disease progression was observed in patients with varying degrees of initial contralateral stenosis, serial clinical and duplex scanning in all patients undergoing unilateral CE is recommended. PMID- 8356527 TI - Personal experience of right anterior segmentectomy (segments V and VIII) for hepatic malignancies. AB - BACKGROUND: Right anterior segmentectomy is the most difficult type of hepatic resection to perform and is reported only rarely. For patients with tumors limited to the anterior segment but complicated by mild liver dysfunction, this is the only type of hepatectomy that can be tolerated. This article described personal experience with this operation in 17 patients with liver malignancies. METHODS: Fourteen patients had hepatocellular carcinoma, one had cholangiocellular carcinoma, and two had metastases, one from rectal and the other from gastric carcinoma. Except in one case of dense adhesion of the hepatoduodenal ligament, hemihepatic vascular occlusion was used. Both the right and middle hepatic veins were fully exposed in 14 patients. RESULTS: The average operation time was 412 minutes and the average blood loss was 1482 ml. There was one operative death as a result of pneumonia and liver failure. Another patient had prolonged bile leakage with right pleural effusion and bleeding gastric erosions. The cumulative 1- and 5-year survival rates were 88% and 47%, respectively. CONCLUSIONS: The results of this experience indicate that in selected patients with hepatic malignancies this procedure is safe and compatible with improved survival. This may be the first report to describe the clinical features and operative technique in a series of patients treated by right anterior segmentectomy. PMID- 8356528 TI - Significance of hepatic vein reconstruction in hepatectomy. AB - BACKGROUND: To preserve remnant liver function, hepatectomy combined with hepatic vein (HV) reconstruction was performed in resection of the tumor located at the confluence of the HV and inferior vena cava. METHODS: Eight patients underwent HV reconstruction: the right HV in three, the middle HV in four, and the left HV in one. An external iliac vein graft was used in two patients, a superficial femoral vein graft in three, and a long saphenous vein graft in one. In one patient a patch graft was applied to the right HV; another patient underwent end-to-end anastomosis of the right HV without grafting. RESULTS: There were no operative deaths and liver function was adequate throughout the postoperative period. Complications included two cases of minor biliary fistula. The middle HV with a saphenous graft and the left HV with an external iliac graft became occluded because of size mismatch at the anastomosis. Six veins were patent at 1 month and three were still patent after 30 months. CONCLUSIONS: To prevent graft occlusion, it is important to select an autologous vein of optimal size and avoid inflammation of the liver stump. HV reconstruction appears to be a new surgical option for patients undergoing hepatectomy. PMID- 8356529 TI - Cystic enlargement of extrahepatic bile ducts. AB - BACKGROUND: Cystic enlargement of the extrahepatic bile duct system is a rare abnormal finding. A congenital origin is usually supposed; however, the pathogenesis is unknown. We report on our experience with extrahepatic bile duct cysts with special regard to cause, treatment, and recurrent disease. METHODS: From 1976 to 1991, 13 patients, 35 to 74 years of age, were treated for extrahepatic bile duct cysts. Seven patients had previously undergone cholecystectomy. Two patients were admitted because of recurrent disease; neither had undergone curative resection. RESULTS: In 11 patients a biliojejunal anastomosis with a Roux-en-Y was created after cyst resection; one patient underwent a diverticular stalk resection with end-to-end anastomosis of the choledochal duct. After a mean follow-up of 68 months eight of 10 patients were alive, two of whom complained about cholangitis. Recurrent diffuse dilatation of the remaining choledochus developed in one patient; one other patient died of cholangiocellular carcinoma 2 years after operation. CONCLUSIONS: In patients who had undergone previous cholecystectomy or with recurrent disease an acquired malformation cannot be excluded. Surgical treatment is always indicated because of imminent complications and should aim at complete resection of cystic tissue. Periodic postoperative evaluation is necessary to detect recurrent disease and malignant transformation. PMID- 8356530 TI - Preoperative chemotherapy and radiotherapy for cancer of the esophagus. AB - BACKGROUND: We wished to determine the role and significance of preoperative chemotherapy and radiotherapy in management of operable cancer of the esophagus. METHODS: Twenty-two patients with clinical stage I-II cancer of the esophagus were entered in a prospective study of preoperative chemotherapy (5 fluorouracil/cisplatin) and radiotherapy (3405 cGy) administered concomitantly during 21 days followed by restaging and total esophagectomy. RESULTS: Five patients did not complete the protocol (three had toxicity, one refused surgery, and one had interim distant metastasis). Seventeen patients underwent total esophagectomy with cervical anastomosis. Two postoperative deaths resulted from sepsis. Thirteen (76%) of 17 patients were considered to have complete clinical response (esophagoscopy and computed axial tomographic scanning) before surgery, but only 5 (29%) of 17 were free of cancer. The median survival was 18 months (median follow-up 57 months). No difference in survival was seen between complete and partial pathologic response. CONCLUSIONS: (1) Preoperative chemotherapy and radiotherapy did not result in increased survival compared with historic controls (surgery alone). (2) Preoperative chemotherapy and radiotherapy clinical staging overestimates the incidence of complete tumor response. (3) Combination chemotherapy is well tolerated, but until newly developed drugs show their efficacy for treatment, surgery should continue to be the major modality for local control and an integral part of clinical investigational trials. PMID- 8356531 TI - Postoperative mental confusion--association with postoperative hypoxemia. AB - BACKGROUND: Postoperative confusion is a well-known complication, but the pathogenetic mechanisms, of which hypoxemia may be one, are not completely understood. METHODS: Thirty otherwise healthy patients undergoing major abdominal surgery and ten patients undergoing middle ear minor surgery, all under general anesthesia, were monitored for oxygen saturation (SpO2) with a pulse oximeter on a preoperative night and on the second night after operation (11:00 PM to 7:00 AM). All patients were tested with a mental test questionnaire (the Hodkinson modification of the original Roth-Hopkins test) before operation and on the third and seventh day after operation. RESULTS: Postoperative hypoxemia did not develop in patients undergoing minor surgery, whereas major surgery was associated with severe constant and episodic hypoxemia on the second postoperative night (p < 0.05). The patients undergoing major surgery had decreased mental function on the third day (p < 0.05) but not on the seventh day after operation, whereas minor surgery did not impair mental function. There was a significant correlation between mental function on the third day after operation and mean SpO2 on the second postoperative night after major surgery (rs = 0.53, p < 0.005) and minor surgery (rs = 0.74, p < 0.03). After major surgery there was also a correlation between decrease (preoperative to postoperative) in mental function on the third postoperative day and mean SpO2 on the second postoperative night (rs = -0.40, p < 0.04). During stepwise multiple regression analysis in patients undergoing major surgery, a significant relationship was found between postoperative mental test score and SpO2 (p < 0.05) but not between mental function and other perioperative variables (age, premedication dose, duration of operation, and intraoperative and postoperative opioid dose). CONCLUSIONS: These results suggest postoperative hypoxemia to be an important pathogenetic factor in postoperative mental dysfunction. PMID- 8356532 TI - Perioperative immune modulation. AB - BACKGROUND: The effects of operative trauma on systemic immunity were studied. The relative effects of skin incision and of breaching the peritoneum were determined. In addition, the role of the antiendotoxic agent taurolidine in preventing postoperative immune suppression was assessed. METHODS: Systemic immune responsiveness was measured as the delayed-type hypersensitivity (DTH) response to 2-4 dinitro l-fluorobenzene (DNFB) with an in vivo rat model. The effect of both laparotomy and taurolidine on the hepatic Kupffer cell population was determined by immunohistochemistry. RESULTS: This study confirmed that cellular immunity is significantly depressed after laparotomy (15.5%; range, 2.5% 24.0%) compared with unoperated controls (26.77%; range, 9.2%-38.0%). Opening the peritoneum appeared to be a critical factor in inducing this immunosuppression, in which animals undergoing a similar midline incision without opening of the peritoneum displayed minimal alteration in their DTH response (20.5%; range, 0.85%-41.5%). In addition, intraperitoneal administration of taurolidine in the perioperative period prevented this decrease in postoperative DTH response. Kupffer cell numbers were increased after intraperitoneal administration of taurolidine, compared with animals treated with intraperitoneal saline solution or unoperated controls. CONCLUSIONS: These findings confirm the presence of an operatively induced decrease in immune responsiveness and suggest that entering the peritoneum is an important factor in the induction of this effect. In addition, administration of taurolidine acts to prevent the impact of laparotomy on DTH response, possibly by preventing perioperative portal endotoxemia. PMID- 8356533 TI - Complex iliac arterial trauma: autologous or prosthetic vascular repair? AB - The methods for vascular reconstruction of iliac arterial trauma can be a challenging problem. Primary arterial repair is usually possible, but an extensive injury may require interposition grafting or extra-anatomic bypass. Some investigators have advocated prosthetic grafting as a reasonable method of repair for complex iliac arterial injuries. We challenge this concept and describe our experience with the exclusive use of autogenous vascular repair during involvement with 87 consecutive patients surviving iliac arterial trauma. PMID- 8356534 TI - Our technique of parathyroid autotransplantation in operation for papillary thyroid carcinoma. AB - BACKGROUND: For papillary thyroid carcinoma, we have used our standard operative method consisting of total thyroidectomy, bilateral lymph node dissection, and parathyroid autotransplantation. Our special parathyroid transplantation method involves transplantation of the minced glands into the pectoralis major muscle. We investigated whether this method is useful for preserving parathyroid function. METHODS: In 17 patients who underwent our standard operation for papillary thyroid carcinoma, the intact parathyroid hormone (PTH) and serum calcium levels were determined for 4 weeks after the operation. RESULTS: In all cases the intact PTH levels fell below detectable limits immediately after operation and then recovered to the preoperative level about 2 weeks after the operation. The same recovery patterns were observed in two groups undergoing transplantation of two glands and three or four glands. CONCLUSIONS: These recovery patterns of intact PTH levels seem to indicate that the glands were grafted successfully and recovered their function. Our method is thought to be useful for preserving parathyroid function after surgery. PMID- 8356535 TI - Preimplant radiographic assessment of available maxillary bone support. Comparison of tomographic and panoramic technique. AB - For maxillary implants it is essential that presurgical radiographic examination provides reliable assessment of the available bone support. Radiographic confirmation of the inclination of the alveolar crest is also necessary, to select optimum sites for insertion of implants. When preimplant radiographic assessment is based solely on a panoramic radiograph, only the bone height can be assessed and not the available bone volume or the inclination of the alveolar crest. Tomographic examination techniques allow for assessment not only of available bone height and volume but also of the inclination of the crest. In the present work tomographic and panoramic examinations of two cases are compared. The radiographic appearance of different alveolar crest forms is discussed. For preimplant assessment of the maxilla, tomography is the method of choice. PMID- 8356536 TI - Dental health in suburban Jordanian preschool children. AB - There is no previous report from Jordan on dental health in preschool children. In the present study, carried out from November 1988 to January 1989, 255 Jordanian children aged 6 months to 6 years and living in a suburb of Amman were examined for dental caries and related factors. The disease was clinically visible in the second year of life. In the age group 3-6 years 72% had acquired caries, most of them severe. Boys and girls were affected similarly. The prevalence of caries was independent of social background factors. The reason for the high prevalence was probably early and uncontrolled intake of sweets combined with absence of dental cleaning. The authors pose that dental caries is becoming a major health problem among suburban Jordanian children and propose that this preventable disease should be tackled a the child health centers through teaching programmes directed to parents, commencing when the child is under one year of age. PMID- 8356537 TI - Development of periapical lesions. AB - The purpose of the present study was to follow the development of periapical lesions both radiographically and histologically in infected teeth with open and sealed root canals. The mandibular premolars from five adult monkeys were used in the experiment. Sealed infected teeth developed radiographic signs of periapical pathosis significantly earlier than unsealed teeth. Although, histological signs of pathology could be seen periapically at earlier observation periods, sealed teeth consistently developed these changes earlier than unsealed teeth. Furthermore, the histological periapical pathology differed somewhat between the two groups in that unsealed teeth showed a multi-focal diffuse pattern of spreading. PMID- 8356539 TI - [Review of a technic for the estimation of area under the concentration curve in pharmacokinetic analysis]. AB - The determination of the area under concentration-time curve (AUC) is the most important parameter of a non-compartmental pharmacokinetic analysis. The calculation of AUC is usually performed by the trapezoidal rule. The aim of this work is to examine the reliability of this method still considered as a reference. The trapezoidal rule was compared to a selection of calculation methods often owning to other fields of research i.e., rectangular rule, Simpson and Tchebychev rules and log trapezoidal rule. The specific interest and limits of each method were discussed according to the kind and the type of pharmacokinetic profiles i.e., logarithmic or nonlogarithmic and the number of concentration-time couples. We obtained the following results: 1) The rectangular rule is the most simple and less effective method. 2) The trapezoidal rule remains an interesting method particularly when the profile is monologarithmic or nonlogarithmic. The efficacy of this method increases with the number of points of the pharmacokinetic profile. 3) The Simpson and the Tchebychev rules give very good results particularly when the number of points is higher than 7 and 6 respectively. 4) The log trapezoidal rule is an excellent method for the treatment of a logarithmic profile. 5) Both Tchebychev and log trapezoidal rules give accurate results when compared to the true AUC values. Further, it must be pointed out that this determination is depending on an arbitrary choice of points. Finally, the trapezoidal rule is not always the best method to determine AUC. If the analyst has only a pocket-calculator, he will obtain best results with the Simpson method than with the trapezoidal rule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356538 TI - Local inflammatory reactions in juvenile and adult rats. AB - The present investigation was designed for the study of the early phases of local inflammatory reactions in juvenile and adult rats. A recently developed experimental model, based on continuous diffusion of an inflammation inducing agent, was applied. Thirty-five juvenile (6 weeks) and thirty-five adult (6 months) rats were used. Two sterile teflon tables were implanted subcutaneously on the back of each animal on each side of the midline. After three weeks, when a connective tissue capsula had developed, the tablets were replaced by one test tablet (containing lipopolysaccharide) and one fresh teflon tablet, respectively. In each group five animals were sacrificed on day 0 and fifteen animals on each of day 7 and 21. Biopsies comprising tablet and surrounding tissue were taken and exposed to routine histological treatment. The total number of cells was assessed in four defined areas in connection with each tablet. Cells classified as leukocytes were recorded separately. The analysis was performed at 1000x magnification in a light microscope. During the first seven days an increase in the number of leukocytes was seen in the tissue adjacent to the test tablets in both young and adult rats. After 21 days the number of leukocytes was still high in the adult group while in the juvenile group the number of leukocytes returned to the base-line level. PMID- 8356540 TI - [Review and use of decision rules for bioequivalence trials]. AB - To declare bioequivalent two different formulations of one active drug, bioavailability studies are conducted, usually based on area under the plasma concentration-time curves and peak concentrations. The decision follows a statistical basis with right statement of the hypotheses of bioequivalence that are described. This procedure allows to control the consumer risk of falsely accepting bioequivalence while minimizing the new formulation risk of erroneously rejecting bioequivalence. Six decision rules meeting these criteria are reviewed and compared with numerical data: classic confidence interval; symmetric confidence interval; Hauck-Anderson method; two one-sided tests procedure; bayesian method; non parametric confidence interval. The six rules all have very similar performance. However, the bayesian procedure which gives a probability of the location of the true relative bioavailability could likely complete the two one-sided tests procedure and/or the classic confidence interval method that are recommended in regulatory guidelines. Some other statistical points that have received different interpretation in the international regulations are finally evoked and discussed. PMID- 8356541 TI - Pharmacokinetics of acipimox and of its N-deoxy metabolite following single and repeated oral administration to healthy volunteers. AB - The aim of the present study was to evaluate the plasma pharmacokinetics of acipimox and of its N-deoxy metabolite (5-methylpyrazine-2-carboxylic acid, MPCA) following single and repeated administration of 250 mg acipimox (thrice daily, for 6 days) to ten healthy volunteers. Mean maximum concentration, the corresponding time, area under the curve extrapolated to infinity and elimination half-life values of acipimox after single administration were equal to 5.74 micrograms/ml (range 2.56-8.38 micrograms/ml), 1.7 h (1-3 h), 16.99 micrograms/ml.h (11.28-22.17 micrograms/ml.h) and 1.15 h (0.79-1.48 h), respectively. Mean area under the curve over one dosing interval (8 h) and elimination half-life values of acipimox after repeated dosing were not significantly different from the corresponding values after the single dose. No significant accumulation was observed following the repeated treatment, since the mean accumulation ratio was 1.08 (range 0.74-1.52). The mean maximum concentration and corresponding time values in the 7 out of 10 subjects with detectable metabolite levels after the single dose were 0.19 microgram/ml (0.10 0.34 microgram/ml) and 6.7 h (3-12 h), respectively, whilst after the repeated treatment, detectable concentrations of the metabolite were observed in all subjects, the mean maximum concentration value being equal to 0.48 micrograms/ml (0.11-1.19 microgram/ml). The average ratio of the parent/metabolite area under the curve values (8 h) after repeated dosing was equal to 14 (range 2-56). Inter subject variability in the extent of metabolite formation was very high. PMID- 8356543 TI - [Zopiclone. Data of experimental pharmacology and clinical use]. AB - Zopiclone is the first of the cyclopyrrolones, a new class of psychotropic agents which is chemically different from the benzodiazepines (BZD). From an experimental point of view it has qualitatively the pharmacological profile of the tranquilizer-hyponotics, and activity quantitatively differs from hypnotic BZD by its lower myorelaxant. The electroencephalographic studies also demonstrated that its power spectrum is characteristic of a product having a tranquilizing hypnotic potential. The cyclopyrrolones interact with GABA ergic neurotransmission, and have a high affinity for GABA receptor complex. They act on sites close to BZD sites, but physically different. The sleep polygraphic studies have shown that zopiclone has a specific profile. It respects the sleep architecture, specially the delta sleep which is even increased, in some studies. Its residual effects are absent or minimal, and its acceptability is good in the usual conditions of hypnotic prescription. PMID- 8356542 TI - [Pharmacokinetic and clinical evaluation of rectal hydrophilic gel of methohexital in pediatric surgery]. AB - The purpose of the study was to develop and to test a new form of rectal systemic gel for methohexitone administration in children undergoing minor surgery. Pharmacokinetics of methohexitone were determined in children following intravenous or intrarectal administration either at low or therapeutic dosage. Anaesthesic efficacy of this gel was performed in 11 patients receiving a therapeutic dosage (25 mg/kg). Pharmacokinetics of methohexitone appears independent of both dosage and route of administration in children. The bioavailability of the rectal gel appears sufficient to provide efficient clinical plasmatic concentrations. As a consequence of the rapid and good resorption of methohexitone from rectal lumen and of the low variability of plasmatic concentrations, a rapid and reliable sedation was observed in all patients. The clinical anaesthesic efficacy of the rectal hydrophilic gel associated with the absence of an apparent local intolerance and important side effects, make this new form suitable for methohexitone administration in children. PMID- 8356544 TI - Medications exposure during pregnancy. A study in a university hospital. AB - To collect informations about drugs prescribed during pregnancy in France we carried out a retrospective survey from august to december 1989. This study was based on a questionnaire at delivery for 225 women. Socio-economic status, obstetrical past history and patterns of prescribing medications were studied. 99.5% of the women were found to have used drugs during pregnancy with a mean of 6.84 medications per woman. There was no influence of age, geographic origins, number of previous pregnancies on drug consumption; socio-professional status was also found to have a poor correlation with drug intake. Patterns of prescribing were compared to those of a previous French study made in 1976: changing pattern of prescribing were found for progestatives, corticoids, neurotropes, aspirin and beta adrenergic agents. We also pointed out that self-administered drugs decreased from 25.9 to 17.9%. This evaluation supports the need of further epidemiological studies in our country. PMID- 8356545 TI - [Possible exploitation of a pharmacovigilance center concerning the risk of teratogenesis]. AB - Evaluating a teratogenic risk remains a difficult problem, since the existing data in this field is fragmentary. One can consider using the material obtained by the follow-up of pregnancies which have motivated a telephone consultation to an Information Center. The material could, within limits, be used to give some security. If the present numbers do not change, it would take around four years to obtain data concerning 150 women exposed during the first trimester of their pregnancy. PMID- 8356546 TI - [Collection of familial data in pharmacogenetics. Methodological problems]. AB - The purpose of this paper is to show the problems with family data collection in a pharmacogenetic study, the aim of which was to study the genetic polymorphism of inducibility of cytochromes P4501A by polycyclic aromatic hydrocarbon (PAH). Data were collected from 76 smoker nuclear families (315 volunteers). A caffeine test, a blood sample and answers to a questionnaire were obtained from each healthy volunteer. It was a crucial problem to recruit nuclear families with healthy smoker father and/or mother and 2 smoker children. On 127 answers, 22 families were not eligible, 27 refused and 10 had a single child, that meant secondary refusals. Problems differed with origin of the recruitment. Included were 40 families obtained from 3 antismoking outpatient departments, 29 from general practitioners but 6 only from students. The family rates with 2 parents/2 children were significantly higher with general practitioners (p < 0.01). This emphasized their part in epidemiologic studies. Problems with the use of methodology were bound to acceptability of the tests which were better in females (p < 0.05), and a change in caffeine form could improve this acceptability. Lastly, difficulties with laboratories constraints required a very good coordination between families, nurses and laboratories. PMID- 8356547 TI - [Survey of the incidence of undesirable events in geriatric services]. AB - In elderly with the risk of side effects of drugs is more important due to the age-related changes in organs and the drug interactions. It's why 26 gerontologic centers performed a multicentric survey about side effects (SE) incidence during a short period of 15 days. This survey was realised by REGATES (Network of Evaluation in Gerontology of Activity of Treatments and Side Effects). 2829 patients were included (8% acute patients, 23% Geriatric medicine, 69% nursing home). 74 SE were noticed in 64 patients among 21 centers. There were 23 men and 41 women with an average age 81.2 +/- 6.5 y. taking 5.7 +/- 1.6 drugs/per day. The main SE were neurological or cardiovascular (26% each). SE incidence is high with extrapolation 636 SE per year for 1000 geriatric patients. Considering the 100,000 hospital beds for elderly, we may measure the lack of informations which don't reach the pharmacovigilance centers, in relation to the weak medical density. PMID- 8356548 TI - [Value of the study of the stability of diltiazem and its metabolites in blood samples]. PMID- 8356549 TI - [Bupivacaine concentration in newborn infants after epidural maternal anesthesia]. PMID- 8356550 TI - Troleandomycin hepatotoxicity: a case report of overt jaundice and a placebo controlled trial. PMID- 8356551 TI - [Ventricular arrhythmia during fluvoxamine poisoning]. PMID- 8356552 TI - [Interaction between fluvoxamine and tricyclic antidepressants. Some precise details]. PMID- 8356553 TI - [Accidents with antivitamin K. Advantages of benefits over risks]. PMID- 8356554 TI - [Reversible cardiomyopathy induced by interferon]. PMID- 8356555 TI - [Hepatic involvement associated with indapamide therapy]. PMID- 8356556 TI - [Furosemide (Lasilix) can be used in patients with G6PD deficiency. Apropos of a case]. PMID- 8356557 TI - [Myasthenia induced by thiopronine in rheumatoid polyarthritis]. PMID- 8356558 TI - Changes in the prescription patterns for hypercholesterolaemia in Upper Normandy. PMID- 8356559 TI - [Value of the theory of the optimal sampling scheme for bioequivalence studies]. AB - Use of optimal sampling theory (OST) in pharmacokinetic studies allows a large reduction of the number of sampling times without loss in parameter estimation precision. OST has been applied to the determination of bioavailability parameters [area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration, (Tmax)]. Three different Monte-Carlo simulations in twelve subjects have been performed, corresponding to different pharmacokinetic models: one-compartment with or without a lag time, two-compartment. Bioavailability parameters were estimated using a non-compartmental method (with 12 to 16 sampling times) and OST method (6 to 7 sampling times). Estimates were compared with true values. Bias and RMSE were similar with both methods for AUC and Cmax, while Tmax was better estimated using OST method. However, when a posteriori identifiability of the model was poor, use of a maximum a posteriori Bayesian estimator improved considerably the efficacy of OST method. Potential interest of OST for increasing statistical power of bioequivalence studies at the same cost is discussed, as well as possible limitations. PMID- 8356560 TI - Adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in AIDS. PMID- 8356561 TI - Weight gain under oral testosterone undecanoate in AIDS. PMID- 8356562 TI - [Study of the transplacental transfer of interferon alfa-2a on the model of isolated perfused cotyledon]. AB - Interferon can be used for VIH+ pregnant women, to decrease materno-fetal contamination. Added to maternal circulation, its behaviour was studied by human placental cotyledon ex vivo perfusion. Human recombinant IFN 2a and reference substance 3H2O were injected in intervillous chamber and their behaviours in venous fetal and maternal circulations was followed. At steady state, in fetal circulation 3H2O concentration was 37% of injected rate whereas no IFN transfer rate was observed. In both venous circulations IFN amounts were lower than injected ones 56% versus of 82% for water (p < 0.05). IFN didn't cross placental filter and disappeared partially during placental contact. PMID- 8356564 TI - Rodent tissue distribution of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile. AB - The direct acting mutagen 2-cyanoethylene oxide (CEO), formed in the liver by oxidation of acrylonitrile (ACN), is thought to mediate the extrahepatic carcinogenic effects of ACN in rats. This study determined the tissue distribution of CEO (3 mg/kg p.o.) in F-344 rats and B6C3F1 mice. Radioactivity from [2,3-14C]CEO was widely distributed in the major organs of rodents by 2 h and decreased by 71% to 90% within 24 h, demonstrating that there was no preferential tissue uptake or retention of CEO. CEO was detected in rodent blood and brain 5-10 min after an oral dose of ACN (10 mg/kg), demonstrating that this mutagenic epoxide metabolite circulates to extrahepatic target organs following ACN administration. PMID- 8356563 TI - Toxicity evaluations of L-cysteine and Procysteine, a cysteine prodrug, given once intravenously to neonatal rats. AB - Decreased enzymatic production of cysteine in premature and newborn infants may limit the synthesis of glutathione. Unfortunately, cysteine supplementation is limited by associated toxicity and product instability. Procysteine (L-2 oxothiazolidine-4-carboxylate) is a prodrug of cysteine that is inert until metabolized to cysteine intracellularly, thus stimulating glutathione synthesis. The potential toxicities of cysteine and Procysteine were compared in two studies with neonatal rats (10 per group; 3 +/- 1 days of age) after a single intravenous administration. In one study, acute high dosage survivorship was compared for approximately equimolar cysteine dosages of L-cysteine and Procysteine. Mortality at 7 days after single intravenous dosages of L-cysteine at 1.52 or 1.14 g/kg or Procysteine at 1.80 or 1.35 g/kg was 80, 50, 10 and 0%, respectively. Clinical pathology parameters and body and organ weights were compared in a second study, following a moderate dosage of Procysteine or equimolar or lower dosages of L cysteine. No differences were observed in clinical pathology parameters nor body or organ weights at 14 days following single intravenous dosages of L-cysteine at 369, 185 or 37 mg/kg or Procysteine at 450 mg/kg. Also, Procysteine solutions were considerably more stable than L-cysteine solutions (months vs. hours, respectively). These studies indicated that cysteine supplementation in infants may be enhanced by Procysteine administration. PMID- 8356565 TI - Stimulation of protein kinase C by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat thymocytes. AB - Exposure of immature thymocytes to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (10 nM) transiently increased detergent extractable protein kinase C (PKC) activity. The increase was apparent at 7.5 min after exposure of cells to TCDD. At later time points, PKC activity returned to control values. Addition of TCDD to cytosol significantly increased phospholipid-stimulated PKC activity. Thus, stimulation of PKC activity may be one of the early events affected by TCDD. PMID- 8356566 TI - Subchronic toxicity study of methyl hesperidin in mice. AB - A subchronic toxicity study of methyl hesperidin was performed using B6C3F1 mice. The flavonoid was administered to groups of ten males and ten females in dietary levels of 0, 0.3, 0.6, 1.25, 2.5 and 5.0% for 13 weeks. No significant treatment related differences were found in data for body weights, food and water consumption, hematology, clinical chemistry and organ weights. Furthermore, no effects of treatment were observed on gross and histopathological examination of the major organs. The present experiment thus demonstrated that methyl hesperidin exerts no obvious toxic effects in mice of either sex when administered at a level as high as 5.0% in the diet. PMID- 8356567 TI - Maternal and developmental toxicity of manganese in the mouse. AB - Manganese (II) chloride tetrahydrate was investigated in Swiss mice for maternal and developmental toxicity after subcutaneous (s.c.) exposure to doses of 0, 2, 4, 8 and 16 mg/kg per day from gestation day 6 through 15. Females were sacrificed on gestation day 18, and fetuses were examined for external, visceral, and skeletal abnormalities. Maternal toxicity included significant reductions in weight gain and food consumption at 8 and 16 mg/kg/day, as well as several treatment-related deaths in the high dose-group. There were no treatment-related effects on the number of total implants, early resorptions, dead fetuses or sex ratio, whereas a significant increase in the number of late resorptions was found in the 4, 8, and 16 mg/kg/day groups. Fetotoxicity, consisting primarily of reduced fetal body weight and an increased incidence of morphological defects was also observed at 8 and 16 mg/kg/day. There were no differences between control and manganese-treated groups in the incidence of individual or total malformations. The no observable adverse effect level (NOAEL) for maternal toxicity of MnCl2 x 4H(2)0 in mice was 4 mg/kg/day, while the NOAEL for embryo/fetal toxicity was 2 mg/kg/day. PMID- 8356568 TI - In vitro cytotoxicity of 1,4-naphthoquinone derivatives to replicating cells. AB - The acute cytotoxicities of a series of alkyl-1,4-naphthoquinones (NQ) and of 2 hydroxy-3-alkyl-1,4-NQs, as well as some amino derivatives, were evaluated with the neutral red cytotoxicity assay, using BALB/c mouse 3T3 fibroblasts. As compared to the unsubstituted 1,4-NQ: (i) Substitution at the 2 position reduced toxicity, with the extent of reduction following the sequence, hydroxyl >> dimethylamino >> C1-C5 alkyl group. (ii) Substitution with C2-C5 alkyl groups at position 3 enhanced toxicity. As noted with the n-alkyl-1,4-NQs, increasing the chain length of the 2-hydroxy-3-alkyl-1,4-NQs did not appreciably change potency of the test agent. (iii) Substitution with amino groups at position 3 had little effect on cytotoxicity. Some differences in cytotoxicity of specific test agent were noted between the 3T3 fibroblasts and isolated rat hepatocytes, as reported in the literature. PMID- 8356569 TI - The mechanism of chloroform toxicity in isolated rat hepatocytes. AB - Chloroform (CHCl3) is widely used in the manufacture of drugs, cosmetics, plastics and cleaning agents. It is also found in chlorinated drinking water. This study was designed to investigate the toxic effect of CHCl3 on isolated male rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and the cell viability was determined by Trypan blue exclusion. The leakage of cytosolic enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) after treatment with CHCl3 was measured. Reduced glutathione content (GSH) and its related enzymes, glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px), were also evaluated to study the effect of CHCl3 on hepatocytes. Exposure to 100 and 1000 ppm CHCl3 results in a significant decrease in cell after 30 min incubation. However, the effect of 1 and 10 ppm concentrations was observed at 60 min incubation. AST leakage was significantly increased in all treatment groups, while ALT was significantly increased at 100 and 1000 ppm CHCl3 after 60 and 30 min, respectively. As early as 15 min, GSH was decreased significantly at 1000 ppm, but at 100 and 10 ppm CHCl3 the decrease in GSH began after 30 and 120 min, respectively. GSH-Px activity did not changed. However, the activity of GSH-Rx was significantly decreased at 1000 ppm CHCl3 and at the same time GSH content was decreased. The data indicate that the toxic effect of CHCl3 was dose- and time-dependent. The degree of GSH depletion correlated with increased cytotoxicity and decreased GSH-Rx activity due to CHCl3. PMID- 8356570 TI - The mechanism of methyl mercury toxicity in isolated rat hepatocytes. AB - Mercury is the major component of dental amalgam restorative material, which typically has 50% pure elemental mercury. It is also used in some skin creams, and in the manufacturing of plastic, drugs and fungicides. The present study was designed to investigate the toxicity of methyl mercury (MeHg+) on isolated rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and were incubated with different concentrations of MeHg+ (0.1-100 ppm) for 2 h. Through the incubation period the viability was determined by Trypan blue exclusion. Reduced glutathione (GSH) content and its enzymes, glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-RX) were measured. Leakage of enzymes such as aspartate transaminase (AST), and alanine transaminase (ALT) were determined. The cell viability was reduced significantly after 1 h incubation when 0.1 and 1 ppm MeHg+ were applied. The decrease in the cell viability was dose- and time-dependent. A depletion of GSH content was observed with 100 ppm MeHg+ after 30 min of incubation. A significant decrease in GSH-RX was observed with 100 ppm during 15 and 30 min of incubation, while 10 ppm of MeHg+ significantly increased ALT leakage after 60 min. However, there was a significant increase in AST leakage with 100 ppm only. The present investigation indicates that the toxic effect of MeHg+ is most likely cytosolic enzyme related. PMID- 8356572 TI - Transformation of estrone, estradiol, and estrone sulfate in uterine and vaginal isolated cells of fetal guinea pig. Effect of various antiestrogens in the conversion of estrone sulfate to estradiol. AB - The metabolism of physiological concentrations (5 x 10(-9) M) of [3H]estrone (E1), [3H]estradiol (E2), and [3H]estrone sulfate (E1S) was studied in isolated fetal uterine and vaginal cells of guinea pigs in culture. After 24 hours of incubation in both cells, a large percentage (40-60%) of E1 is converted to E2; however, after incubation of E2, most of the radioactive material (45-65%) corresponds to unchanged E2. Similarly, in the incubation medium the concentration of E2 is significantly higher related to E1 after incubation with E1 or E2. An intense sulfotransferase activity is found for both estrogens, whereas in the culture medium the respective sulfates represent 27-45% of the total radioactive material after incubation with the uterine cells and 15-24% for the vaginal cells. Using E1S, significant hydrolysis is observed in both cells and the analysis of the freed radioactive material indicated a high percentage in E2 (66% in the uterine cells and 71% in the vaginal cells). The conversion of E1S to E2 was strongly decreased by the antiestrogens: tamoxifen, 4-hydroxy tamoxifen, and ICI 164,384. The inhibitory effect in relation to the incubation with E1S only was 43-66% in the uterine cells and 50-85% in the vaginal cells. The present data suggest that estrogen sulfates can play an important biological role in the target tissues of the fetus, and that the enzymatic mechanisms of the bioavailability of E2 for the biological responses of the hormone can be operated in the target tissue itself. PMID- 8356571 TI - Tetrapropylammonium perruthenate as a mild and efficient oxidant for sensitive steroidal alcohols. AB - Tetrapropylammonium perruthenate N-methylmorpholine N-oxide oxidation of steroidal alcohols is described. The reagent combination is mild and gave good yields of the corresponding ketones. Although the oxidation can generate ketones from 3-, 11-, 15-, 17-, and 20-hydroxy steroids, the oxidation of homoallylic alcohols proceeds in low yields. Finally, we observed that the oxidation reagents will convert 17 alpha-hydroxy-20-keto steroids to 17-keto systems in excellent yield. PMID- 8356573 TI - Alteration in proliferative and endocrine responsiveness of human mammary carcinoma cells by prototypic tumor-suppressing agents. AB - The experiments performed in this study were designed to establish that (1) acquisition of anchorage-independent growth, a biological characteristic of tumorigenically transformed phenotype, can be modulated by prototypic tumor suppressing agents, and (2) modulation of growth is influenced by the metabolic competence of the cells to biotransform estradiol, MCF-7 human breast carcinoma cells exhibited linear cell proliferative kinetics with a 41-hour population doubling time, and a 15% colony-forming efficiency in 0.33% agar. Indole-3 carbinol (13C), a naturally occurring tumor-suppressive agent; tamoxifen (TAM), an antiestrogenic agent; and 4-hydroxytamoxifen (4-OHTAM), a metabolite of TAM, demonstrated 73.7%, 72.5%, and 89.9% suppression in anchorage-independent growth of MCF-7 cells, respectively. At the metabolic level, 13C and 4-OHTAM induced 2.3 fold (P < 0.0001) and 1.3-fold increase (P = 0.001) relative to their own controls in the extent of 2-hydroxylation of estradiol. The results indicate that growth inhibition by 13C, TAM, and 4-OHTAM may in part be due to altered estradiol metabolism in MCF-7 cells. Thus, anchorage-independent growth and altered biotransformation of estradiol may constitute useful cellular and endocrine markers to evaluate the biological response of chemosuppressive agents. PMID- 8356574 TI - Steroids 49. Investigations on the dehydration of 17 alpha-ethynyl-17 beta hydroxysteroids. AB - The acidic dehydration of 17 alpha-ethynyl-17 beta-hydroxysteroids (1-3) was investigated. On reaction with thionyl chloride, phosphorus oxychloride, and formic acid, the desired dehydration was accompanied by chlorination, Wagner Meerwein rearrangement, and D-homoaromatic rearrangement. The structure of the product from the transformation of 17 beta-hydroxypregn-20-yne derivative (3) on reaction with formic acid was misjudged. It was regarded as a pregn-16-en-20-yne (10) instead of the actually rearranged D-homoaromatic compound (11). As a consequence, physical data corresponding to this latter structure have been cited in the literature as those of pregn-16-en-20-yne derivative (10). This confusion prompted us to prepare compounds of both types (4, 9, 10, and 11), the characterization of which is here described. PMID- 8356575 TI - The ozonation of cholesterol: separation and identification of 2,4 dinitrophenylhydrazine derivatization products of 3 beta-hydroxy-5-oxo-5,6 secocholestan-6-al. AB - The ozonation products of cholesterol, which are of interest as possible biomarkers of O3 exposure, were studied by derivatization with 2,4 dinitrophenylhydrazine (DNPH). The DNPH derivatization of 3 beta-hydroxy-5-oxo 5,6-secocholestan-6-al (2) produces the expected trans (3b) and cis (3c) derivatives of 3 beta-hydroxy-5-oxo-5,6-secocholestan-6-al, and the unexpected DNPH derivative of 3,5-dihydroxy-B-norcholestane-6-carboxaldehyde (3a). The structures of 3a, 3b, and 3c were identified with 1H nuclear magnetic resonance (NMR), 13C NMR, DEPT, COSY, and H-C correlation two-dimensional NMR techniques, and by comparison with the spectra of known compounds. A possible mechanism involving an enamine functionality is proposed for the formation of 3a. The ratio of 3a/(3b + 3c) depends on the concentration of acid used and the reaction time. PMID- 8356576 TI - Human placental cholesterol side-chain cleavage: enzymatic synthesis of (22R)-20 alpha,22-dihydroxycholesterol. AB - (22R)-20 alpha,22-Dihydroxycholesterol is the second intermediate in the conversion of cholesterol to pregnenolone by cytochrome P450scc in steroidogenic tissues. We report a rapid method for the enzymatic synthesis of (22R)-20 alpha,22-dihydroxycholesterol from (22R)-22-hydroxycholesterol using mitochondria from the human placenta. PMID- 8356577 TI - Preparation of 16-formylestradiol and the 16-(alpha-methylenebutanolide) derivative. AB - Routes to the preparation of 16-formylestradiol are described. Estrone was converted to (E)-16-methoxymethylene estrone via the 16-hydroxymethylene estrone. Reduction of the methoxymethylene estrone with NaBH4 in the presence of CeCl3 gave 16-methoxymethylene estradiol. Deprotection by acid afforded the desired 16 formylestradiol. Attempts to prepare the 16-formylestradiol via the 16 butylthiomethylene derivative gave only 16-formylestra-1,3,5(10),16-tetraen-3-ol, and a route through the 16-dimethoxymethyl derivative gave a mixture of the 16 formyltetraen-3-ol and the 16-formylestradiol in low yield. The 16 formylestradiol was subsequently converted to the alpha-methylene lactone conjugate, 4-(3,17 beta-dihydroxyestra-1,3,5(10)trien-16-yl)-2-methylene-4 butanol ide by reaction with methyl alpha-(bromomethyl) acrylate and zinc. PMID- 8356578 TI - Rejection of cultured keratinocyte allografts in presensitized mice. AB - The fate of cultured keratinocyte (KC) allografts remains controversial. Although prolonged survival of cultured KC allografts in naive mice has been reported, the detailed mechanisms remain undetermined. Furthermore, it was also reported that in the human cultured KC allografts do not survive permanently, and they are rapidly replaced by recipient cells. In the present study, we have addressed this issue and obtained findings that cultured KC allografts survive for a prolonged period in naive mice under the conditions in which reepithelization by recipient cells is prevented. However, the same cultured KC allografts were rejected when they were grafted onto recipients primed with allogeneic spleen cells or full thickness skin grafts. To clarify the mechanisms behind these findings, the allostimulatory ability of cultured KC and their susceptibility to alloreactive cytotoxic T cells were examined in vitro. In a mixed epidermal cell-lymphocyte reaction, cultured KC were unable to induce allospecific proliferative responses of naive T cells. On the other hand, primed T cells from presensitized mice showed weak but significant proliferative responses against allogeneic KC. It also was confirmed that cultured KC are susceptible to lysis by alloreactive cytotoxic T cells. These data indicate that prolonged survival of cultured KC allografts in naive mice is attributable to a defect in the afferent, but not the efferent, phase of the rejection process that is caused by the weak allostimulatory ability of cultured KC. This assumption was also supported by the finding that spleen cells from the recipient mice bearing long-surviving KC allografts retain in vitro responsiveness against stimulator cells syngeneic to the grafted KC. Taken together, these findings indicate that long-term survival of cultured KC allografts in naive mice may be due solely to the weak allostimulatory ability of cultured KC, but not to loss of susceptibility to alloreactive cytotoxic T cells after culture of KC or induction of tolerance in the recipient mice bearing KC allografts. PMID- 8356579 TI - Minimum number of islets required to maintain euglycemia and their reduced immunogenicity after transplantation into diabetic mice. AB - In streptozocin (SZ)-induced diabetic mice, 200 islets, but not 50 islets, consistently restore euglycemia within 1 week of transplantation. To determine the minimum number of islets sufficient to maintain euglycemia in a diabetic mouse, we first transplanted 50 and 150 syngeneic islets simultaneously into the right (RK) and left kidney (LK), respectively, and then removed the LK 1 week post-transplantation. The remaining 50 islets maintained euglycemia in 8 of 11 mice with normal intravenous glucose tolerance tests (IVGTT). Protection of 50 islets for at least 7 days was necessary because removal of the 150 islets at 5 or 3 days resulted in a much lower incidence of persistent euglycemia. Similarly, 25 islets were capable of maintaining euglycemia in 2 of 9 mice once hyperglycemia was reversed by split-transplantation of 25 (RK) and 175 (LK) islets. To examine if 50-islet allografts survive longer than 200-islet allografts, we split-transplanted 50 DBA/2 islets in the RK and 150 islets of either B6 (syngeneic), DBA/2 (allogeneic), or C3H/He (third party allogeneic) mouse origin in the LK in 3 groups of diabetic C57BL/6 (B6) mice. The survival of 50 DBA/2 islets in each group after removal of the LK on day 7 was compared to that of 200 DBA/2 islets in control B6 mice. Maximum prolongation of allograft survival was obtained with 50 DBA/2 islets that were split-transplanted with syngeneic B6 islets. These results clearly demonstrate that 50 islets are sufficient to maintain normal glucose tolerance once euglycemia is induced by transplantation of a larger number (i.e., 200) of islets and that 50 islet allografts are much less immunogenic than 200-islet allografts. PMID- 8356580 TI - Rapamycin: immunosuppression, hyporesponsiveness, and side effects in a porcine renal allograft model. AB - Rapamycin prolongs allograft survival and induces donor-specific tolerance in some small animal transplant models. Large animal studies, however, are limited. We studied rapamycin in a porcine renal allograft model. Donor-recipient combinations were chosen based on high response in pretransplant MLCs. Allografts were anastomosed to the aorta and vena cava and the native kidneys removed. There were 5 treatment groups: (a) no immunosuppression; (b) triple therapy (CsA, 1 mg/kg/day; AZA, 2-3 mg/kg/day; and PRED, 3-4 mg/kg/day); (c) rapamycin (0.75 mg/kg/day i.m.) in carboxymethylcellulose (CMC); (d) rapamycin (0.25 mg/kg/day i.m. in CMC); and (e) a vehicle (CMC) control. Serum creatinine levels were determined every other day. Most allografts were biopsied once a week. Immunosuppression was stopped after 30 days. Mean graft survival in nonimmunosuppressed recipients was 6.8 +/- 3.6 days. Mean graft survival in triple therapy recipients (n = 10) was 45.7 +/- 36 days vs. 59.6 +/- 11.4 days in rapamycin (0.25 mg/kg/day) recipients (n = 7) (P = 0.51). Both triple therapy and rapamycin improved renal allograft survival versus nonimmunosuppressed controls (P = 0.0025 and 0.001, respectively). Serum creatinine levels were significantly lower (P < 0.05) in rapamycin versus triple therapy recipients. We conclude that rapamycin is a potent immunosuppressant in a porcine renal allograft model and may avoid the elevated serum creatinine levels associated with CsA. PMID- 8356581 TI - The effects of cold preservation on steatotic graft viability in rat liver transplantation. AB - Clinical experience suggests that grafts obtained from steatotic livers result in primary nonfunction more frequently than those from nonsteatotic livers. To date, however, only a few studies have been done to verify the accuracy of this observation. To investigate the effects of cold preservation on steatotic liver viability, liver grafts obtained from rats fed with a choline-deficient diet were transplanted after periods of cold preservation. Recipient survival rates with normal liver grafts were 8/8 (100%) and those with steatotic liver grafts were 7/8 (88%) (P > 0.05) after 1-hr preservation with UW solution. After 9-hr preservation, however, these rates decreased significantly to 0/8 (0%) with steatotic grafts (P < 0.01), but were not significantly decreased with normal grafts. LDH levels in the effluent at the time of transplantation were 133 IU/L (1-hr) and 512 IU/L (9-hr) in normal livers, but in steatotic livers these were elevated to 598 and 3141 IU/L, respectively (P < 0.01). Recovery rates of hepatic blood flow measured by laser Doppler flowmeter after revascularization were 99% (1-hr) and 96% (9-hr) in normal grafts, but in steatotic grafts they were 98% (1 hr) and 63% (9-hr, P < 0.01). In addition, the oxidative phosphorylation ability of liver mitochondria obtained from steatotic grafts was decreased significantly after cold preservation. The present results suggest that steatotic liver grafts are prone to lose their viability more easily than normal liver grafts after prolonged periods of cold preservation due to a combination of causes. PMID- 8356582 TI - Storage of porcine pancreatic digest prior to islet purification. The benefits of UW solution and the roles of its individual components. AB - The aim of this study was to establish the beneficial effect of storage of pancreatic digest in University of Wisconsin solution on porcine islet purification, the mechanism of this effect, and the components of UW responsible. Ten porcine pancreata were collagenase-digested, and samples of digest were washed and stored for 1 hr in either UW or minimum essential medium at 4 degrees C, prior to separation on continuous linear density gradients of bovine serum albumin. Samples of digest from a further ten pancreata were similarly treated, comparing storage in MEM, UW, and five solutions varying in lactobionate:chloride ratio and raffinose content. The purity of the islet preparations and the densities of islets and exocrine tissue were determined from insulin and amylase assay of aliquots aspirated from these gradients. Washing and storage of digest in UW markedly improved islet purity, compared with MEM, due to an increase in the density of exocrine tissue. Exocrine tissue density following storage was dependent upon the control of acinar cell volume, rather than exocrine enzyme discharge, and was determined primarily by the chloride:lactobionate ratio of the storage solution. Raffinose was of little additional benefit, while the beneficial effect of UW was greater than that due to its lactobionate and raffinose content alone. In conclusion, inadequate purification of islets results from exocrine tissue swelling. This swelling is reduced by storage of the pancreatic digest in UW solution, due primarily to the replacement of chloride by lactobionate in UW. PMID- 8356583 TI - The significance of a positive flow cytometry crossmatch test in primary kidney transplantation. AB - This study was conducted to determine the efficacy of the T cell flow cytometry crossmatch (T-FCXM) test in 841 first cadaver donor transplants. Results showed one-year graft survival rates were 82% for T-FCXM-negative patients, compared with 75% for T-FCXM-positive patients (P = 0.01). Early one-month graft failure was 13 percentage points higher in those with a positive T-FCXM than those with a negative T-FCXM. The positive crossmatch patients also had more frequent immunological failures. A positive T-FCXM was found in 39% of the sensitized patients (PRA > 10%) and 8% of those who had not been sensitized. Patients with a positive T-FCXM in either category had a 74% graft survival rate. Thus, most of the T-FCXM-positive results occurred in patients with complement-fixing antibodies. It is suggested that flow cytometry crossmatching (FCXM) be used prospectively, despite the fact that many patients with a positive crossmatch did have successful transplants (TXs). In the current climate of a cadaver kidney scarcity and large recipient waiting pools, utilization of kidneys for patients with the highest probability of success seems a most prudent policy. PMID- 8356584 TI - The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens. AB - To characterize factors of importance for the occurrence of acute rejection as well as study the impact of these episodes on long-term renal survival and function, a total of 819 acute rejection episodes were studied in 951 primary cadaveric donor kidney recipients (CD) and in 396 primary living donor kidney recipients (LD). The patients were treated by three immunosuppressive schedules, namely, CsA given in a high dose, a medium dose, or a low dose. Additionally, all patients received PRED and patients in the low-dose group received AZA. The incidence of acute rejection was higher and occurred earlier after transplantation in the CsA medium dose and low dose groups than in the CsA high dose group (P < 0.05 and P < 0.01, respectively). Although the incidence of first acute rejection was similar in CD and LD patients, 59.1% vs. 60.6%, it was successfully reversed by antirejection treatment in a higher percentage in LD patients. The estimated graft half-life was shorter in patients who had acute rejection episodes than those who did not, 6.6 years vs. 12.5 years in CD patients (P < 0.0001). Renal function at 1-5 years after transplantation was stable, but significantly poorer in CD patients who had experienced acute rejection than in patients who had not, with the mean creatinine clearance rates in the ranges 45-47 vs. 54-60 ml/min in the other groups (P < 0.0001). In a stepwise Cox regression analysis in CD recipients, risk factors for acute rejection were CsA (low dose) treatment schedule, immunization as displayed by presence of panel-reactive antibodies and positive B cell cross-match, young recipient age, disease of diabetes mellitus, and HLA-DR mismatching. In LD recipients, the corresponding risk factors were treatment schedule, young recipient, HLA mismatching, and transplantation from parent to child. Thus, the study has demonstrated some factors of importance for acute rejection episodes in CsA-treated patients as well as showing the detrimental effect of these episodes on long-term graft survival and renal function. These results suggest that a primary aim of future treatment strategies should be to reduce the incidence of these episodes. PMID- 8356585 TI - The unreliability of the lidocaine/monoethylglycinexylidide test for assessment of liver donors. AB - The serum monoethylglycinexylidide (MEGX) level 15 min (t15) after i.v. administration of lidocaine (1 mg/kg) in liver donors was retrospectively correlated with graft outcome and early hepatic function. Among the 35 orthotopic liver transplants studied, 4 recipients had to be retransplanted within 10 days post-OLT because of early graft nonfunction or dysfunction, and 3 recipients died, with a median (range) donor MEGX t15 (ng/ml) of 100 (86-119) and 169 (146 182), respectively. The remaining 28 OLT patients living with functioning grafts had a donor MEGX of 87 (18-245). No significant correlations could be found between donor MEGX t15 and recipient mean and peak glutamic-oxaloacetic and pyruvic transaminases, total serum bilirubin, or mean and minimum prothrombin time values studied from day 1 to day 5 post-OLT. Moreover, categorization of donors using the MEGX t15 cut-off point of 80 ng/ml could not predict liver graft quality, as previously suggested. In summary, MEGX t15 in liver donors correlated neither with graft outcome nor with early functional parameters. Accordingly, the MEGX test should not be used as an isolated discriminatory evaluation for organ utilization. PMID- 8356587 TI - Suppression of HLA-specific alloantibodies by high-dose intravenous immunoglobulins (IVIg). A potential tool for transplantation of immunized patients. AB - Renal transplantation in patients presenting end-stage renal failure can be hampered by the presence of alloantibodies against HLA antigens. In 4 out of 5 patients with HLA-specific alloantibodies waiting for a renal allograft, treatment with high-dose i.v. Ig resulted in a prolonged suppression (over 3 months) of most of the panel-reactive anti-HLA antibodies (PRA). Intravenous polyclonal human Ig (IVIg) and F(ab')2 fragments from IVIg inhibited the binding of patients' plasma and IgG fractions to peripheral blood lymphocytes from normal donors as well as their cytotoxicity, suggesting that the in vivo effect of IVIg was mediated by the presence, in the IVIg preparation, of anti-idiotypes directed against idiotypes borne on the anti-HLA antibodies. Thus, treatment with IVIg can be a valuable tool toward the transplantation of immunized patients. PMID- 8356586 TI - The appearance of donor heparin in the recipient after reperfusion of a liver graft. AB - The release of heparin has been mentioned as one of the causes of hypocoagulability after reperfusion of the liver graft. It has been ascribed to endogenous heparin released from the donor liver or to exogenous heparin in the preservation fluid that is released into the recipient after sequestration into the graft during preservation. The aim of this study was to investigate whether systemic administration of heparin to the donor before the hepatectomy contributes to the appearance of heparin in the recipient after reperfusion. We studied 20 patients undergoing an auxiliary heterotopic liver transplantation; 15 donors had received heparin immediately before circulation arrest (median 300 IU/kg body weight), but 5 had not. The thrombin time (TT), activated partial thromboplastin time (aPTT), and heparin neutralization test were determined at several intervals during the transplantation. PMID- 8356588 TI - A comparison of preoperative and postoperative nutritional states of lung transplant recipients. AB - Malnutrition is a documented problem in some types of endstage lung disease (ESLD). Recently, isolated lung transplants have successfully reversed the respiratory failure of patients suffering from ESLD. In this study, we compare the preoperative and postoperative nutritional states of lung transplant recipients using weight-to-height ratios, anthropometric measurements, subjective global assessment, and biochemical blood values. Patients with emphysema, cystic fibrosis, and other types of bronchiectasis, but not patients with pulmonary fibrosis or pulmonary hypertension, were malnourished preoperatively. All groups had normal biochemical profiles. Caloric intake of patients with cystic fibrosis and bronchiectasis was increased above predicted basal energy expenditure levels. By six months to one year postoperatively, all groups of malnourished patients had significantly improved their nutritional status. Emphysema patients improved nutrition by maintaining preoperative caloric intake levels--however, both cystic fibrosis and bronchiectasis patients were able to achieve the same goal with significantly decreased caloric intakes. We conclude that malnourished ESLD patients receiving isolated lung grafts are able to achieve normal nutrition within one year posttransplant. Since this occurs in all cases with a reduced, or at best maintained, caloric intake, more study is needed to elucidate the factors that contribute to ESLD malnutrition. PMID- 8356589 TI - Preclinical studies for adoptive immunotherapy in bone marrow transplantation. Generation of anti-CD3 activated cytotoxic T cells from normal donors and autologous bone marrow transplant candidates. AB - In order to obtain T cells for adoptive immunotherapy after autologous bone marrow transplantation (ABMT) for patients with resistant hematological malignancies, a culture system was developed for growing T cells and inducing non MHC-restricted cytotoxicity using anti-CD3 monoclonal antibody (OKT3) activation. In this investigation, we show that (1) peripheral blood lymphocytes or bone marrow mononuclear cells (BMMNC) from normal donors and cancer patients can be activated with OKT3 and grown in interleukin-2; (2) normal BMMNC activated with OKT3/IL-2 exhibited non-MHC-restricted cytotoxicity and surface markers comparable to that exhibited by normal PBL activated with OKT3/IL-2; (3) both proliferation and cytotoxic functions were IL-2-dependent; (4) PBL activated with OKT3/IL-2 after cryogenic storage grew and killed comparable to PBL activated with OKT3/IL-2 prior to cryopreservation; (5) OKT3/IL-2-activated PBL and BMMNC obtained from 5 patients with non-Hodgkin's lymphomas (NHL) and 1 patient with acute myelogenous leukemia (AML) increased cell numbers 41-75-fold in 2 weeks of culture; 5 of 6 patients with NHL or AML had PBL and BMMNC that exhibited cytotoxic activity; and (6) contaminating leukemic cells did not overgrow in OKT3/IL-2-activated cultures and could no longer be detected on cytospin specimens after 3 weeks of culture. These data show that T cells in PBL or BMMNC from ABMT candidates can be activated with OKT3/IL-2 for adoptive immunotherapy in combination with ABMT. PMID- 8356590 TI - The hemodynamic effects of intraoperative injection of muromonab CD3. AB - During anesthesia 5 mg of muromonab CD3 (OKT3), an anti-CD3 monoclonal antibody, was administered prophylactically to twelve patients undergoing cadaveric renal transplantation. Preoperatively, all patients were at or near their dry body weights. Methylprednisolone 500 mg on call to or in the operating room, azathioprine 2 mg kg-1 and diphenhydramine 50 mg were administered intraoperatively to reduce the probability and severity of reported effects of OKT3. After induction of anesthesia, the patients were monitored for changes in cardiovascular variables for up to 120 min after OKT3 administration. All patients had uneventful anesthetic courses. Analysis of variance showed no significant changes from pre-OKT3 administration in heart rate, mean blood pressure, mean pulmonary artery pressure, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVRI). CVP values were a reliable indicator of PCWP with the correlation coefficient of CVP to PCWP or r = 0.78 (P < 0.00005) and PCWP = .89 x CVP + 3.78. Cardiac index (CI) increased 22% at 105 min (P < 0.05). Systemic vascular resistance index (SVRI) decreased 21% at 105 min (P < 0.05). SVRI was increased 16% at 10 min post-OKT3 (P < 0.05). All of these statistically significant values were within acceptable clinical limits. Euvolemic cadaveric renal transplant recipients receiving prophylactic steroids and diphenhydramine may receive OKT3 in the operating room for induction immunosuppression without any appreciable risk of cardiovascular compromise. PMID- 8356591 TI - Prevention of Pneumocystis carinii pneumonia in cardiac transplant recipients by trimethoprim sulfamethoxazole. AB - Pneumocystis carinii pneumonia (PCP) continues to cause significant morbidity in recipients of solid-organ transplants. While some programs administer trimethoprim-sulfamethoxazole (TMP-SMX) prophylactically following transplantation, a prospective determination of the safety and efficacy of TMP SMX in cardiac transplant recipients has not previously been reported. We therefore prospectively randomized 58 cardiac transplant recipients to receive TMP (160 mg)-SMX (800 mg) twice daily either three days per week (group B), or seven days per week (group C), or to receive no treatment (group A). Treatment began 14 days after transplantation and continued for four months. Age, sex, preexisting pulmonary pathology and immunosuppressive protocols did not differ among the groups. Of 17 patients in the control group (A), 7 developed a clinical syndrome compatible with PCP, with the diagnosis histologically confirmed by bronchoalveolar lavage during the first four months following transplantation. In contrast, no patients in either the daily or intermittent therapy groups developed PCP during the study period (P < 0.005). Both doses of TMP-SMX were well tolerated, and discontinuation of therapy was not necessary in any patient. Total white blood cell count, azathioprine dose, and number of treated episodes of rejection per patient did not differ among the three groups. We conclude that TMP-SMX can safely and effectively be administered to prevent the occurrence of P carinii pneumonia during the first four months following cardiac transplantation. PMID- 8356592 TI - The endocrine pancreas in brain-dead donors. A prospective study in 25 patients. AB - To determine whether hyperglycemia in brain-dead donors is a sign of endocrine pancreas insufficiency, we studied pancreatic function in 25 consecutive brain dead patients. Blood samples were drawn at 2-hr intervals from donor referral until organ procurement to analyze glucose, insulin, and C-peptide levels. After donor retrieval, two specimens were taken from the pancreas for a subsequent immunohistochemical examination. At referral mean glycemia was 13.60 +/- 1.49 mmol/L, and there was a large range of plasma glucose levels (4.6-31.6). Of 25 patients, 16 had glycemia above 10 mmol/L. At organ procurement a mean of 20 hr later, mean glycemia as 8.61 +/- 0.58 mmol/L (P < 0.005 with paired t test), and only 5 patients had glycemia above 10 mmol/L. Hyperglycemia was associated with elevated insulin and C-peptide levels during donor management. An elevated C peptide/glucose molar ratio might be considered a sign of peripheral insulin resistance. Hyperglycemia above 25 mmol/L could not be related to the amount of glucose administered during donor maintenance. Severe hyperglycemia had a natural tendency to be partly corrected. Histologic and immunohistochemical examinations were available in 17 cases and can be considered normal. It is concluded that endocrine pancreatic function can be considered effective after brain death. The mechanism of the relative insulin resistance of these patients requires further study. Blood glucose levels, in the range observed in this study, are not a good donor criterion of endocrine pancreatic function before pancreas transplantation. PMID- 8356594 TI - The effect of donor-recipient strain combination on rejection and graft-versus host disease after small bowel/liver transplantation in the rat. AB - The initial clinical experience with simultaneous small bowel/liver transplantation (SBL) suggests that liver grafting may protect the small bowel from rejection. A pilot study of SBL in DA (RT1a) rats with Lewis (RT1l) allografts in our laboratory provided experimental support for this concept. However, the clinical applicability of the data was questioned because the transplants were performed in a low-immune-responder rat strain combination. This study examined the outcome of SBL in several rat strain combinations. Isolated small bowel transplants (SB) and SBL were performed in three groups: DA-->PVG (low immune responder), BN-->LEW (intermediate immune responder) and ACI-->LEW (high immune responder). Lewis-->Lewis isografts were used as controls. All of the rats with SB rejected their allografts, whereas all of the rats with simultaneous liver grafts had minimal or no signs of intestinal rejection. The outcome of SBL was profoundly affected by the donor-recipient strain combination. The low immune responders developed severe graft-versus-host disease. The intermediate immune responders developed mild-to-moderate GVHD and moderate liver rejection. The high immune responders developed severe liver rejection. In this study, the outcome of small bowel transplantation depended upon the strain combination used and whether or not a simultaneous liver graft was transplanted. The immune interactions that occur after multi-visceral transplantation are complex and cannot be easily predicted. PMID- 8356593 TI - The antilymphocytic activity of brequinar sodium and its potentiation by cytidine. Effects on lymphocyte proliferation and cytokine production. AB - Based on its capacity to inhibit de novo pyrimidine biosynthesis by blocking dihydroorotate dehydrogenase activity, the antitumor agent brequinar sodium (BQR) has emerged as a new immunosuppressive agent. Since BQR is known to prevent the synthesis of nucleotides during cell proliferation, we hypothesized that it would be highly effective in controlling strong lymphocyte proliferative responses but might be less effective in controlling comparatively weak responses that do not necessarily involve new nucleotide synthesis. We addressed this question by culturing murine spleen cells with different types of stimuli, including Con A, phorbol myristate acetate +/- ionomycin, anti-CD3, and anti-Igs. Addition of BQR (0.001 microgram/ml to 10 micrograms/ml) at the start of a 72-hr culture period caused dose-dependent inhibition of strong proliferative responses, induced either by Con A (5 micrograms/ml) or PMA+ionomycin. A residual degree of proliferation persisted, however, even at the highest BQR concentrations. In contrast, no impairment of low-concentration Con A (0.5 or 0.1 microgram/ml), anti-CD3, or anti-Igs responses was observed. In order to ascertain its role in arresting nucleotide synthesis, we attempted to reverse the inhibitory effect of BQR by adding exogenous uridine or cytidine to lymphocyte cultures. BQR's inhibitory activity was reversed completely by adding uridine at 0.1 mM. In contrast, combination of BQR and cytidine (0.1 mM) potentiated BQR's activity and abrogated anti-CD3 or anti-Igs-induced lymphocyte proliferation in a dose dependent manner. A synergistic inhibitory action between BQR and cytidine was observed when the BQR concentration was higher than 0.1 microgram/ml and with cytidine at 0.1 mM. Production of interleukin-2 and IL-4 was only slightly affected by BQR, but was significantly suppressed by coadministration of BQR and cytidine. Neither BQR (5 micrograms/ml) on its own, however, nor combination of BQR with cytidine affected production of mRNA for IL-2, IL-4, or interferon gamma, as determined by reverse-transcription polymerase chain reaction. Our observations suggest that BQR may not only affect dihydroorotate dehydrogenase activity, but may also inhibit the enzyme cytidine deaminase, which converts cytidine to uridine. These antimetabolic effects of BQR complement the well-known cytokine synthesis inhibitory actions of FK506 or CsA. The combination of BQR and cytidine, however, offers a further possibility for inhibition of both cytokine production and T and B cell proliferation, and may have potential for the control of graft rejection. PMID- 8356595 TI - Abrogation of secondary skin allograft rejection by veto-like cells in donor bone marrow. AB - To investigate whether a veto cell phenomenon is involved in the ability of donor strain bone marrow cells (BMC) to inactivate second-set skin graft rejection induced by the adoptive transfer of sensitized spleen cells (SSC), mice were grafted with ear skin allografts and injected on the following day with recipient strain SSC or SSC plus donor strain BMC. When skin and BMC donors from an F1 strain (B6AF1) were combined with a parental strain (C57BL/6) as recipient and SSC donors, the BMC were fully active in abrogating second-set rejection even though the SSC were naturally tolerant of the BMC. Thus, immunological recognition of the SSC by the BMC is not necessary for this abrogation. The suppressive activity of the BMC is specific in a manner similar to that reported for veto cells (i.e., they suppress an anti-self response). If BMC from various strains of mice were used to alter the rejection of C3H grafts by B6AF1 recipients, only BMC expressing the MHC antigens to which the SSC had been sensitized significantly suppressed the activity of SSC. Sharing of additional antigens between the graft and BMC (e.g., MHC antigens not recognized by the SSC or minor antigens) was neither necessary nor sufficient. Mitomycin C-treated BMC were unable to inhibit SSC-induced accelerated rejection. Overall, the characteristics of the SSC-suppressive activity of BMC are consistent with a veto cell nature of the BMC. PMID- 8356596 TI - Induction of TNF alpha and TNF beta gene expression in rat cardiac transplants during allograft rejection. AB - The expression of the cytotoxic cytokines tumor necrosis factor alpha and TNF beta or lymphotoxin (LT) was assessed in rat cardiac transplants during rejection. Newborn rat cardiac grafts placed in adult rat ear pinnae were retrieved on days 1 through 10 posttransplantation; the average time to rejection, assessed by the absence of detectable electrocardiographic activity, was determined to be 7 days. Total cellular RNA and tissue homogenates were prepared from cardiac transplants in order that relative levels of TNF alpha and LT mRNA and TNF protein could be determined. A biphasic pattern of TNF alpha gene expression was consistently seen in cardiac allografts. TNF alpha mRNA transcripts were detected as early as day 2 post-tx, with peak levels appearing on day 3 post-tx. Although transcript levels decreased by day 4, a significant increase appeared again on day 6 post-tx, coincident with the onset of rejection. Similar to TNF alpha gene expression, LT transcripts demonstrated a biphasic pattern of induction. LT mRNA transcripts also reached peak levels on day 3 post tx, with a second increase in transcript levels coincident with rejection. TNF protein levels in allografts displayed a biphasic pattern, similar to that shown by the cytokine mRNAs. Peak levels of TNF protein were detected on day 3 post-tx, with a second increase again coinciding with rejection. In contrast to TNF expression found in allografts, TNF alpha and LT mRNA transcripts were not detected in isografts on days 1 through 10 post-tx. TNF protein levels in cardiac isografts were consistently at or below the standard limits of detection, and on days 3 through 7 post-tx were significantly reduced (P < or = 0.001) when compared with time-matched allografts. Increased expression of the cytotoxic cytokines TNF alpha and LT, therefore, appears to be allograft-specific and is an early event during rat cardiac allograft rejection. In conclusion, induction of TNF gene expression may be an important early indicator of transplant rejection. PMID- 8356597 TI - Similar levels of granzyme A and perforin mRNA expression in rejected and tolerated heart allografts in donor-specific tolerance in rats. AB - Congenic LEW.1W (RT1u) heart grafts in LEW.1A (RT1u) recipient rats are rejected within 15 +/- 6 days. Tolerance (> 100 days) can be induced by pretransplant donor-specific blood transfusions. In both cases, the graft is heavily infiltrated by recipient cells, and class I and class II molecules of the major histocompatibility complex are strongly expressed. Moreover, T lymphocytes extracted from both tolerated and rejected grafts are similarly cytotoxic in vitro against donor cells. However, it cannot be excluded that this cytotoxicity does not operate in vivo. To answer this important question, we have studied the expression of granzyme A and perforin mRNA expression, in situ, by Northern blotting. Our data show that the two corresponding mRNAs accumulate with the same kinetic and at the same level in rejected and tolerated grafts. These results strongly suggest that infiltrating cells are cytotoxic in vivo and that a "cellular rejection" does occur in the "tolerated" grafts. In addition, these findings show that cytotoxic T lymphocytes are not sufficient to impair graft survival and lead to a revaluation of the relevance, in general, terms of granzyme and perforin expression as a correlate of rejection. PMID- 8356598 TI - Acute graft-versus-host-like disease induced by transplantation of human activated natural killer cells into SCID mice. AB - Whereas T lymphocytes are essential for the initiation of acute graft-versus-host disease (aGVHD), it is not at all clear whether they or other cells or noncellular factors actually mediate the characteristic lesions. This report describes the in vivo effects of human NK cells, T cells, and cytokines on the induction of aGVHD in 4 Gy sublethally irradiated C.B-17 scid/scid (SCID) mice. Human NK and T lymphocytes were obtained separately by antibody- and complement mediated negative selection from the peripheral blood of normal donors and expanded in medium containing rIL-2 and irradiated autologous feeder cells. The characteristics of the two groups of cells were analyzed before injection into SCID mice. Cytofluorometric phenotyping demonstrated that 70-95% of NK-enriched cells expressed CD3-, CD16+, CD56+, and CD8-dim+; ninety-seven per cent of T cells expressed CD3+, TCR-alpha/beta+, CD4+, or CD8-bright+. Analysis of K562 and Daudi cultured target cell lines demonstrated 40-50% higher cytotoxicity by NK enriched cells as compared with activated T lymphocytes. TNF-alpha cytokine production was greatly increased in activated NK cells (250 pg/ml) as compared with T cells (25 pg/ml) and fresh PBMC (12.5 pg/ml). IFN-gamma was increased in both NK and T cells. After i.v. injection of 1-5 x 10(7) cells into irradiated SCID mice, minor to severe skin lesions, diarrhea, and weight loss occurred in NK but not the T cell-injected animals. In NK-injected animals, thinning and focal loss of epithelium with pyknotic nuclear change and degeneration and loss of skin appendages were observed. Single cell necrosis, crypt abscess formation, and loss of glandular epithelium developed in the colon of NK but not in T cell-injected animals. These findings are very similar to allogeneic aGVHD in SCID mice injected with C57BL/6 mouse splenocytes. Immunohistological staining with anti human CD56, CD3, TNF-alpha, and IFN-gamma antibodies demonstrated CD56+ cells in association with TNF-alpha and IFN-gamma secretion in the bowel of NK-injected animals. CD3+ cells were not found in the same tissues. These findings were not observed in T cell-injected and control mice. In summary, aGVHD-like lesions were induced by transplantation of xenogeneic human activated NK cells into SCID mice. We hypothesize that cytokines released from human NK cells play a central role in the pathogenesis of clinical aGVHD. PMID- 8356599 TI - Modulation of the kinetics of the initial leukocyte migration into renal allografts by 16,16-dimethyl PGE2. AB - Host sensitization to vascular allografts is induced by the interaction between host lymphocytes, antigen-presenting cells, and the allograft. However, little is known concerning the nature or kinetics of the initial host leukocyte migration into the transplanted organ prior to immune sensitization. Employing a model of donor-irradiated renal allografts and isografts, we have characterized the participating cell types and the kinetics of the leukocyte influx during the first 96 hr after engraftment. Both isografts and allografts experience a marked initial influx of host leukocytes into the renal interstitium, peaking at 48 hr after transplantation. Concomitant glomerular accumulation of leukocytes is much less marked. By 96 hr, the leukocyte influx into isografts has significantly diminished, while allografts demonstrate a subsequent additional rise in interstitial leukocytes coincident with the development of allosensitization. In allografts, the predominant cell type in the influx of the first 24-48 hr of the leukocyte influx is the monocyte/macrophage, with a smaller component of T lymphocytes. Neutrophils and B lymphocytes are not found in this initial infiltrate. Intragraft infusion of dimethyl PGE2 markedly inhibits the monocyte influx during the first 24-48 hr into the renal interstitium, but not the glomeruli, of allografts, while having relatively little effect on the migration of leukocytes into the renal glomerulus or renal interstitium of isografts. The results suggest that one mechanism by which PGE may inhibit host sensitization to allografts may be suppression of the initial influx of donor monocytes into the newly allografted organ. PMID- 8356600 TI - Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats. AB - Many severe metabolic deficiencies in children are caused by a single gene defect with a resultant single gene product deficiency. These diseases may be amenable to permanent cure using new techniques of gene transfer and cell transplantation. In many in vivo models of retroviral mediated gene therapy, a significant limiting factor is the ability to transplant a sufficient number of modified cells. To potentially circumvent this problem, we have developed a biodegradable polymer implant system capable of supporting large numbers of genetically modified cells. In this study, we inserted a reporter gene into syngeneic cultured normal fibroblasts and then transplanted these genetically modified cells into animals using synthetic biodegradable polymer fibers as temporary cell delivery scaffolds. To begin to develop a system capable of delivering desirable proteins secreted by genetically modified cells, Fischer 344 adult rat fibroblasts were transduced in tissue culture with a retrovirus containing the reporter gene Lac Z. These genetically modified cells (1.1 x 10(7) cells/graft) were then attached to the biodegradable polymer fibers and the polymer-cell graft was transplanted subdermally into syngeneic recipients (n = 9). There was persistence of the modified cells with expression of the reporter gene for at least 30 days. The estimated number of genetically modified cells per implanted graft decreased from a pretransplant value of 1.1 +/- 0.6 x 10(7) to 3.2 +/- 0.7 x 10(6) by 15 days after transplantation (P < 0.01). Thereafter, the cell number did not vary significantly to the conclusion of the study at day 30 (3.6 +/- 1.0 x 10(6) cells/graft). Evidence of ingrowth and incorporation of other stromal elements was present in the graft by 1 week post-transplantation, as judged by counterstained hematoxylin and eosin micrograph sections. Migration of modified cells to areas outside of the polymer-cell graft was not detected. Over the course of the study, there was little degradation of the polymer implant, although by day 30, evidence of early dissolution was evident. The number of polymer fibers per high power field increased slightly from 62.5 +/- 5.8 on day 1 to 77.3 +/- 26.6 on day 30 (P > 0.2). These data suggest that the use of biodegradable polymer fibers may permit the transplantation of genetically modified cells in sufficient numbers to deliver a therapeutically useful product. Polymer matrices allow for the attachment and site-specific transplantation of genetically modified cells. PMID- 8356601 TI - Continuous systemic secretion of a lysosomal enzyme by genetically modified mouse skin fibroblasts. AB - Lysosomal enzymes secreted or externally supplied into the extracellular medium can be internalized by cells and targeted to lysosomes after binding to specific membrane receptors. This process allows for the replacement of the missing enzyme activity in deficient cells. Using a retroviral vector, we have introduced the human beta-glucuronidase cDNA into primary mouse skin fibroblasts. The genetically modified cells were then engrafted into neo-organs that had been previously implanted into the peritoneal cavity of syngeneic recipient mice. The hypervascularized structures, made of collagen and basic fibroblast growth factor coated synthetic fibers embedded into extracellular matrix gel, allowed in vivo survival of engrafted fibroblasts that expressed the human beta-glucuronidase cDNA for at least 3 months. The human enzyme was detected in the liver, lung, and spleen of experimental animals, but became undetectable after removal of the neo organ. This observation indicated that the human enzyme was secreted into the serum and then captured by distant organs. The use of genetically modified fibroblasts implanted into neo-organs may, therefore, represent a convenient approach to enzyme replacement therapy in lysosomal storage diseases. PMID- 8356602 TI - Ventricular expression of atrial natriuretic peptide after orthotopic cardiac transplantation. AB - In order to determine if atrial natriuretic peptide is produced by the human ventricle after transplantation, specimens were obtained from 54 separate right ventricular endomyocardial biopsies from 14 transplant recipients (age range 10 19 years) and were analyzed with simultaneous plasma samples. Radioimmunoassay techniques were used to determine plasma and tissue levels of atrial natriuretic peptide in each biopsy specimen, and blot hybridizations with the atrial natriuretic peptide c deoxyribonucleic acid probe were performed once for each patient. Mean plasma levels of atrial natriuretic peptide were obtained from the right ventricle (106 +/- 12 pg/ml); there was a positive correlation with end diastolic pressure (r = 0.7, P < 0.0001). Plasma levels, however, were not significantly increased during rejection episodes. Atrial natriuretic peptide was detectable in all ventricular biopsy specimens--mean 989 +/- 164 pg/mg soluble protein. Mean tissue level during rejection episodes was 1163 +/- 17 and following treatment of rejection was 411 +/- 147--however, this difference was not significant (P = 0.55). In 6 patients biopsied within 1 month of transplantation initial myocardial levels were significantly higher than those obtained at the following biopsy (P < 0.05). Despite these initially high tissue levels no correlation was found with time posttransplantation. Ventricular tissue levels positively correlated with systolic ventricular pressure, r = 0.3, P < 0.05, but there was no significant correlation with other hemodynamic parameters. The normalized atrial natriuretic peptide messenger ribonucleic acid signal from the slot blot hybridization was 59 +/- 6 mm (peak height of signal intensity) range 20-110 mm. The expression of atrial natriuretic peptide gene was also confirmed by Northern blot analysis. The ventricular messenger ribonucleic acid signal contained a single hybridizing band of approximately 920 nucleotides. Thus, we have demonstrated that atrial natriuretic peptide production by the human ventricle is independent of innervation. The consistent atrial natriuretic peptide gene expression and detection by radioimmunoassay in apparently healthy ventricles was unexpected but may reflect the use of immunosuppressive drugs, or perhaps subclinical graft dysfunction. PMID- 8356603 TI - Detection of cytokine mRNA in vivo by polymerase chain reaction. Problems and solutions. AB - The expression of cytokine mRNAs in murine sponge matrix graft infiltrates was studied using the polymerase chain reaction (PCR). In infiltrates of both C57B1/6 > C57B1/6 isografts and DBA/2 > C57B1/6 allografts, a similar pattern of cytokine expression was observed. On days 6, 8, and 10 postimplant, mRNAs encoding IL-4, IL-6, and IFN-gamma were detected. On days 8 and 10, mRNAs encoding IL-1 alpha, TNF, and lymphotoxin/TNF beta were also expressed. Surprisingly, no IL-2 mRNA was observed in isografts or allografts. Two modified PCR techniques were utilized to compare the level of expression of cytokine mRNAs in isografts versus allografts and to detect the expression of IL-2 mRNA in this system. A semiquantitative PCR protocol based on limiting cycles of amplification is described that was used to determine the amount of IL-4 mRNA expressed in isograft and allograft infiltrates relative to beta-actin mRNA. Using this method, no difference was found in the amount of IL-4 mRNA in infiltrates of day 8 isografts and allografts. The validation of this technique by analysis of samples with known relative mRNA levels is presented. A nested PCR protocol is described that provided greatly enhanced sensitivity over standard PCR analysis. Using this technique, IL-2 mRNA was detected in infiltrates from sponge allografts on all days tested, beginning on day 2 postimplant. No IL-2 mRNA was detected in isograft infiltrates or in peripheral blood from allograft-bearing animals. The pattern of cytokine mRNA expression observed in sponge matrix allografts is consistent with the presence of a weak alloreactive response superimposed upon an intense granulomatous process that occurs in both the isografts and allografts. This report demonstrates modified PCR techniques that can be used to resolve experimental problems associated with the analysis of cytokine mRNA expression in vivo. PMID- 8356604 TI - Clinically significant anti-A derived from B lymphocytes after single lung transplantation. PMID- 8356605 TI - Jaundice associated with concomitant use of norethandrolone and cyclosporine. PMID- 8356607 TI - Umbilical cord blood transplantation in a patient with Philadelphia chromosome positive chronic myeloid leukemia. PMID- 8356606 TI - Liver preservation with lidoflazine and the University of Wisconsin solution: a dose-finding study. PMID- 8356608 TI - Hamster coagulation and serum proteins in rat recipients of hamster xenografts. PMID- 8356609 TI - Production of interference in the TDx polarization immunoassay by fluorescein angiography. PMID- 8356610 TI - Esophageal candidiasis, omeprazole therapy, and organ transplantation--a word of caution. PMID- 8356611 TI - The genetics of race. PMID- 8356612 TI - Introduction to the African American Histocompatibility Workshop: goals and overview. PMID- 8356613 TI - HLA diversity in African Americans. PMID- 8356614 TI - Association of HLA phenotypes with hypertension in African Americans and Caucasoid Americans with type II diabetes, a population at risk for renal disease. PMID- 8356615 TI - Comparison of HLA phenotypes among African Americans from Alabama, Maryland, and North Carolina. PMID- 8356616 TI - Beneficial effects of HLA-DR3 gene expression on renal allograft survival in black recipients. AB - We have shown that there is a subgroup of black recipients who lack DR3 antigen expression and have decreased graft survival in comparison to black recipients who express DR3 antigen. Overall, the 3-year renal graft survival was equivalent between white and black recipients in our series and white recipients were not affected by DR3 antigen expression. We suspect that altered immune activity in the DR3-positive black patients may afford a benefit in overcoming immunologic barriers. This needs further investigation both in light of the possible association of the linked antigens A1-Cw7-B8-DR3 which are associated with loss of suppressor cell activity, as well as the issue of DR3 subtyping. However, there clearly exists the possibility of targeting higher risk groups such as the DR3-negative black recipients for more intense immunosuppressive regimens as well as eliminating pretransplant transfusion of third-party donors. Finally, we must reconsider the question of whether HLA matching is especially punitive to blacks, since matching for broad DR specificities in black recipients does not necessarily match for subtypes unique to blacks. Modifying or de-emphasizing the UNOS point system for organ allocation based on MHC antigen should be seriously considered as a mechanism for increasing the percentage of black kidney transplant recipients. PMID- 8356617 TI - Presensitization and frequency of positive crossmatches in black and nonblack renal transplant candidates. PMID- 8356618 TI - Risk factors for end-stage renal disease among minorities. AB - Blacks, Hispanics, and American Indians are at increased risk of ESRD. Among blacks, hypertension, type II DM, and possibly type I DM are classic risk factors and pose an increased risk for disease. A unifying concept in both DM and hypertension appears to be increased glomerular pressures. The role of diuretics as an independent risk factor for ESRD is further advanced. At a minimum diuretics appear not to be renal protective. Glomerulonephritis also occurs more commonly in blacks. The underlying pathology is largely unknown. There is an increased rate of HAN- and HIV-associated nephropathy which does not explain the excess risk. Patterns of referral or other biases may be in effect. The increased incidence of ESRD in Hispanics is mainly related to DM although, hypertension also plays a role. There is also evidence that HIV-associated nephropathy may occur relatively more often than in whites. We have alluded to the increased incidence of ESRD among American Indians and noted that diabetes mellitus occurs more commonly in most tribal groups while glomerulonephritis occurs more frequently in the Zuni. That groups at increased risk of ESRD are at the lower spectrum of the SES raises this issue as a common risk factor for disease. It is unlikely that SES is an independent risk factor. Education, access to early interventions, and social behavioral factors must be incorporated into any model which proposes a reduction in the rate of ESRD in these groups. The treatment of hypertension with medications that may be renal protective or pose increased risk, especially insofar as diuretics are concerned, must be considered urgent grounds for future research. PMID- 8356619 TI - Hypertensive renal disease in blacks. PMID- 8356620 TI - Renal microvascular susceptibility in African American pedigrees. PMID- 8356621 TI - Diabetic renal disease: racial and ethnic differences from an epidemiologic perspective. AB - In summary, Native Americans, Hispanics, and blacks are at higher risk of diabetic ESRD relative to whites, particularly among subjects with NIDDM, even after controlling for the higher prevalence of diabetes in these groups. Incidence of diabetic ESRD is increasing in all race and ethnic groups, particularly in Native Americans and Hispanics. This increase may be real or artifactual. Based on the results of a few studies, controlling for several risk factors for diabetic ESRD does not explain the excess risk in blacks and Hispanics. Survival after beginning treatment for diabetic ESRD is longer in blacks, Native Americans, and Asian/Pacific Islanders when compared to whites. Longer survival in blacks compared with whites occurs among dialysis patients, but not in transplant patients, after controlling for type of diabetes and comorbidity present at onset of ESRD. The higher incidence of diabetic ESRD in blacks, Hispanics, and Native Americans, combined with an increased incidence over time and longer survival after ESRD onset, indicate that these racial and ethnic groups will comprise a large portion of diabetic ESRD in the future. PMID- 8356622 TI - Diabetic nephropathy in blacks. PMID- 8356624 TI - A decade of human immunodeficiency virus-associated nephropathy (HIVAN). PMID- 8356623 TI - Improving renal transplant outcomes in African Americans with OKT3 induction therapy. PMID- 8356625 TI - Collaborative Transplant Study analysis of graft survival in blacks. PMID- 8356626 TI - HLA polymorphisms, ethnicity, and graft survival: united network for organ sharing. UNOS Scientific Renal Transplant Registry. PMID- 8356627 TI - Twenty-five-year review of race and transplantation at a single institution. PMID- 8356628 TI - Matching and the black recipient. PMID- 8356629 TI - Decreased HLA matching does not preclude successful renal transplantation in African Americans. PMID- 8356630 TI - Effect of donor race on graft survival in black South African recipients of cadaveric renal allografts. PMID- 8356631 TI - Posttransplant hypertension in blacks versus nonblacks. PMID- 8356632 TI - Effect of recipient race on waiting time for renal transplantation at the University of Pittsburgh. PMID- 8356633 TI - Influence of race on delayed renal allograft function and outcome in the cyclosporine era. PMID- 8356634 TI - Blacks and whites on the UNOS renal waiting list: waiting times and patient demographics compared. PMID- 8356635 TI - Organ allocation: current problems and future issues. PMID- 8356636 TI - In vitro response to immunosuppressive agents in blacks. PMID- 8356637 TI - Influence of length of time on dialysis before transplantation on long-term renal allograft outcome. PMID- 8356638 TI - Correlation of CD3+ lymphocyte depletion with rejection and infection in renal transplants. PMID- 8356639 TI - Cadaveric renal transplant in the highly sensitized African-American patient. AB - A statistically significant difference was discovered when comparing the 1-year graft survival of CAUC and AA. The difference was due in part to nine AA failures that occurred within the first week posttransplant (Fig 3). Using a multivariant analysis both the AA and CAUC were found to be normally distributed in regard to CIT, HLA mismatch, transplant number, and PRA. If these traditional variables thought to have relevance on graft survival in cadaveric renal transplantation are ruled out as contributing factors other avenues must be explored. If credence is given to the theory that the difference in function between AA and CAUC is due to the difference in the number of transplants that failed within the first week then factors such as immunosuppressive therapy and noncompliance can also be ruled out. One possible area of explanation may lie in the area of specificity to HLA antibody. It is possible that these recipients received transplants from a donor to which they were sensitized. A closer analysis of donor and recipient HLA typing as well as the recipient's transfusion and transplant history is recommended. Despite the fact that all transplants occurred in the presence of negative preliminary and final XM's using American Society for Histocompatibility and Immunogenetics (ASHI) certified techniques (Table 2), transplant centers may wish to consider using a more sensitive XM technique such as flow cytometry for these patients. We hope that these recommendations will enable transplant centers to continue their commitment to transplanting the highly sensitized recipient. PMID- 8356640 TI - Hepatic transplantation in the United States. PMID- 8356641 TI - Organ donation and referrals among African-Americans. AB - Solid organ referrals for AA have been growing since 1989. One third of AA referrals are in the 16 to 30 year age group with the majority of these males suffering traumatic injury. AA donors have increased from 11 in 1989 to 32 in 1992. This is in spite of AA and minority consent rates that are 20% to 30% below that of the CAUC group. This gap represents a vital opportunity for improvement. Increased education to minority groups with a message that considers the ethnic and cultural diversity of the minority community coupled with an increase in the number of minority transplant coordinators should help to increase the number of AA referrals and donors. PMID- 8356642 TI - Increasing African American organ donation: the St Louis experience. PMID- 8356643 TI - Review of black donor awareness in New York City. PMID- 8356644 TI - Hispanic experience of organ donation in New York City. PMID- 8356645 TI - Continuing dilemma of organ procurement for clinical transplantation. PMID- 8356646 TI - Moving toward cultural competence in the transplant milieu. PMID- 8356647 TI - Postrenal transplant compliance: report of 519 responses to a self-report questionnaire. PMID- 8356648 TI - Treatment options for end-stage renal disease: patient perceptions and factors influencing choice of modality. PMID- 8356649 TI - Rehabilitation following a kidney transplant. PMID- 8356650 TI - Rehabilitation revisited. PMID- 8356651 TI - Effects of cultural preferences on nutrition. PMID- 8356652 TI - Influence of mind in the healing process. PMID- 8356653 TI - A tribute to Veretta Woodhouse Blake. PMID- 8356654 TI - Summation of the Third International Samuel L. Kountz Symposium on renal disease and transplantation in blacks. PMID- 8356655 TI - Evaluation of preservation of the intra-abdominal organs. PMID- 8356656 TI - Defibrotide use during preservation favors the metabolic function of grafted kidneys in rats. PMID- 8356657 TI - Long-term renal preservation and prevention of acute tubular necrosis by inhibition of arachidonate metabolism. PMID- 8356658 TI - Effects of Carolina rinse on hepatic microcirculation and leukocyte-endothelium interaction in rat liver transplantation. PMID- 8356659 TI - Essential components of Carolina rinse for attenuation of reperfusion injury in rat liver transplantation. PMID- 8356660 TI - Increased flow rate of preservation solution in the hepatic artery during organ preservation can improve postischemic liver function. PMID- 8356661 TI - Platelet-activating factor antagonist BN52021 improves survival in normothermic liver ischemia in rats. PMID- 8356662 TI - Failure of PGE1 to prevent liver allograft reperfusion injury in a prospective randomized trial. PMID- 8356663 TI - Role of eicosanoids in reperfusion injury in rat liver transplantation. PMID- 8356664 TI - Rinsing with warm Ringer's lactate reduces microvascular reperfusion injury in rat liver transplantation. PMID- 8356665 TI - Influence of SOD, catalase, and epoprostenol on 24-hour liver preservation in pigs. PMID- 8356666 TI - Comparison of HTK solution and UW solution in 24- and 48-hour preservation of canine hepatic allografts. PMID- 8356667 TI - Morphological and functional evaluation of the quality of preservation of the rat pancreas. PMID- 8356668 TI - Ex vivo normothermic preservation of rat multiple organ blocks using a perfluorooctyl bromide emulsion as oxygen carrier. PMID- 8356669 TI - Impact of preservation solution on early function and graft survival in cadaveric renal transplantation. PMID- 8356670 TI - Pretransplant assessment of renal viability by using ion-selective electrodes--a pilot study. PMID- 8356671 TI - Transplantation of abdominal organs in children. PMID- 8356672 TI - The Stockholm experience with pediatric renal transplantation. PMID- 8356673 TI - Significance of duplex and color encoded Doppler sonographic monitoring in children with renal transplants. PMID- 8356674 TI - Sequential color and pulsed Doppler sonography for monitoring antirejection therapy in pediatric patients. PMID- 8356675 TI - Comparison of adjusted-dose vs standard-dose OKT3 therapy of acute rejection in pediatric kidney transplant recipients. PMID- 8356676 TI - 24-hour blood pressure monitoring for the control of antihypertensive therapy in pediatric kidney transplant recipients. PMID- 8356677 TI - Long-term effect of cyclosporine on renal function in children after liver transplantation. PMID- 8356678 TI - Growth in children after liver transplantation on cyclosporine alone or in combination with low-dose azathioprine. PMID- 8356679 TI - Hemodynamic changes during intra-abdominal organ transplantation. PMID- 8356680 TI - Hemodynamics during the anhepatic phase in orthotopic liver transplantation with vena cava preservation: a comparative study. PMID- 8356681 TI - Shuntflow vs renal perfusion pressure during venovenous bypass in human orthotopic liver transplantation. PMID- 8356682 TI - Effect of high shuntflows during portofemoro-subclavian venovenous bypass in human orthotopic liver transplantation. PMID- 8356684 TI - Splenic artery steal syndrome after orthotopic liver transplantation: diagnosis and treatment. PMID- 8356683 TI - Continuous indirect calorimetry during orthotopic liver transplantation with and without venovenous bypass. PMID- 8356685 TI - Assessment of microhemodynamics after liver transplantation by in vivo microscopy in the rat. PMID- 8356686 TI - Analysis of hepatic hemodynamics after orthotopic liver transplantation: an experimental study in pigs. PMID- 8356687 TI - Power spectrum analysis of heart rate variability following kidney transplantation. PMID- 8356689 TI - Persistence of abnormal left ventricular filling following renal transplantation. PMID- 8356688 TI - Colour Doppler recording of renal blood flow in kidney grafts. PMID- 8356690 TI - Prevention of early postoperative graft thrombosis in pancreatic transplantation. PMID- 8356691 TI - Causes of early vascular complications in renal transplantation. PMID- 8356692 TI - Kidneys from pediatric donors: a source of increased risk for graft failure in recipients. PMID- 8356693 TI - Causes of early graft failure at less than 12 months after renal transplantation. PMID- 8356694 TI - Effects of piretanide on early graft function in kidney transplantation: a pilot study. PMID- 8356695 TI - Obesity in kidney transplant patients as a risk factor. PMID- 8356696 TI - Diagnostic value of antegrade pyelography in renal transplants: a comparison of imaging modalities. PMID- 8356697 TI - Can split liver grafting increase the overall success rate of liver transplantation? PMID- 8356698 TI - Donor selection and surgical technique for en bloc liver-small bowel graft procurement. PMID- 8356699 TI - Imported grafts in hepatic transplantation. PMID- 8356700 TI - Early graft function in liver transplantation: comparison of two techniques of graft procurement. PMID- 8356701 TI - Procurement, grafting, and early graft function in liver transplantation, including reduced size and split livers from cadaveric and living related donors. PMID- 8356702 TI - Relationship between cytochrome P-450 3A content of orthotopically transplanted liver and postoperative morbidity. PMID- 8356703 TI - Angiography and vascular radiologic intervention before and after liver transplantation. PMID- 8356704 TI - Liver transplantation for posthepatic B-delta cirrhosis: prevention of recurrence with high-dose anti-HBs immunoglobulins. PMID- 8356705 TI - Acute liver allograft rejection and liver function: quantitative evaluation using the [14C]aminopyrine breath test. PMID- 8356706 TI - Reticuloendothelial system clearance capacity following liver transplantation as a predictor of early graft function. PMID- 8356707 TI - General aspects of the pathology of rejection of kidney and liver in the early posttransplant period. PMID- 8356708 TI - Preliminary analysis of HLA matching in pancreas and liver transplantation. Collaborative Transplant Study. PMID- 8356709 TI - Immune monitoring: does the reality fulfill the promise? PMID- 8356710 TI - Relationship between HLA compatibility and first liver allograft survival. l'ESPRIT Study Group. PMID- 8356711 TI - The number of granulocytes in "time-zero" biopsy as a parameter of prognosis of graft function after liver transplantation. PMID- 8356712 TI - Monitoring of plasma endothelin in relation to Doppler signal in human liver transplantation. PMID- 8356713 TI - Leucocyte elastase in the early diagnosis of rejection after liver transplantation. PMID- 8356714 TI - Balancing cyclosporine A nephrotoxicity and rejection late after adult liver transplantation. PMID- 8356715 TI - Cytokine secretion capacity of mononuclear cells in renal transplant recipients: the effect of two different dose schedules. PMID- 8356716 TI - Nitric oxide synthesis during rejection of orthotopic small bowel allografts is not a strain-specific phenomenon. PMID- 8356717 TI - Recurrent HBV/HDV infections under different immunoprophylaxis protocols. PMID- 8356718 TI - Efficacy of rapamycin in orthotopic small bowel transplantation in the rat. PMID- 8356719 TI - A new immunosuppressive drug, brequinar sodium, suppresses liver allograft rejection in the rat. PMID- 8356720 TI - Mizoribine as an alternative to azathioprine in triple-therapy immunosuppressant regimens in cadaveric renal transplantation. PMID- 8356721 TI - Antithymocyte globulin or interleukin 2 receptor antibody for immunosuppressive induction therapy after orthotopic liver transplantation: a follow-up study. PMID- 8356722 TI - Induction therapy with anti-T-lymphocyte globulin following orthotopic liver transplantation. PMID- 8356723 TI - Management of induction phase of immunosuppression in liver graft recipients: prevention of oversuppression by immune monitoring. PMID- 8356724 TI - Significant effect of HLA-DRB1 typing by linkage disequilibrium on kidney graft outcome. PMID- 8356725 TI - Study of the effect of HLA class II antigens (serotyping and mixed lymphocyte reaction) on kidney graft outcome. PMID- 8356726 TI - Complement-dependent immunosuppressive anti-tissue factor monoclonal antibody: the establishment of monoclonal antibodies and their effect on mixed lymphocyte reaction. PMID- 8356727 TI - Lipid peroxidation of parenchymal hepatocytes during cold preservation and after reoxygenation in rats. PMID- 8356728 TI - Childbirth after renal transplantation. PMID- 8356729 TI - Altered disposition of pravastatin following concomitant drug therapy with cyclosporin A in transplant recipients. PMID- 8356731 TI - Financial compensation for cadaver organ donation: good idea or anathema. PMID- 8356730 TI - Influenza vaccine does not cause rejection after cardiac transplantation. PMID- 8356732 TI - Cloned veto cells as immunoregulators. PMID- 8356733 TI - Effect of rapamycin on islet and skin xenograft survival. PMID- 8356734 TI - Tuberculosis control learning games. AB - In teaching health workers about tuberculosis (TB) control we frequently concentrate on the technological aspects, such as diagnosis, treatment and recording. Health workers also need to understand the sociological aspects of TB control, particularly those that influence the likelihood of diagnosis and cure. Two games are presented that help health workers comprehend the reasons why TB patients often delay in presenting for diagnosis, and why they then frequently default from treatment. PMID- 8356735 TI - A study of prescribing patterns with special reference to drug use indicators in Dar es Salaam Region, Tanzania. AB - Drug prescribing patterns were studied in 720 retrospective and 779 prospective outpatient prescriptions from 20 dispensaries in Dar es Salaam region, and these revealed a mean drug exposure of 2.0 and 2.3, respectively. The percentage of patients leaving the dispensaries with no prescribed drugs was 1.3% and 0.7%, respectively. Prescriptions containing antibiotics were 36.8% (retrospective) and 39.8% (prospective), while injections accounted for 24.6% and 34% of the total encounters, respectively. Over 70% of prescriptions conformed to the Tanzania essential drug list (EDP) and/or standard treatment guidelines and consisted of 83.9% and 79.1% generic prescriptions, respectively. Interestingly, only 15% of the surveyed dispensaries had an EDP book and/or calendar. Despite the consulting and dispensing times being short (2.98 min and 77.7 s, respectively), 70% of the patients could remember the dosing instructions. Only 64% of the patients had a minimum physical examination. PMID- 8356736 TI - How can growth monitoring and special care of underweight children be improved in Zambia? AB - Despite widespread promotion and implementation, very few growth monitoring programmes have been evaluated. Where they have, the findings have often been disappointing and the value of routine growth monitoring has been questioned. There is a concern that the process has become more of a weighing ritual rather than growth promotion. This paper highlights the findings of the evaluation study carried out to assess the performance of the Lusaka urban growth monitoring programme in Zambia. The problems faced and reasons are identified and alternate ways of offering the service are presented. Since the shortfalls are not unique to the Lusaka programme, it is hoped that this paper will stimulate a re-think in the way growth monitoring would be best implemented. PMID- 8356737 TI - Indications for operative fracture treatment in tropical countries. AB - In the period 1 January 1987 to 30 June 1989, 3003 operations were performed at the regional hospital of Gbadolite, northern Zaire. In 123 patients fractures were reduced operatively, in 86 patients by internal fixation and in 37 patients by external fixation. There was no additional bone infection after external fixation but six of 28 patients (21%) with internal fixation by plate and screws developed postoperative osteitis. Non-union was observed in 12% after intramedullary nailing, in 4% after screw fixation alone, and 14% after internal fixation by Kirschner wires. Based on these data, indications and contraindications for operative fracture treatment in tropical countries are defined. PMID- 8356738 TI - Spectrum of cholangitis in a rural setting in North-eastern Peninsular Malaysia. PMID- 8356739 TI - Statistics of perinatal mortality due to error or omission: a suggestion of how to improve care. PMID- 8356740 TI - Missed dislocation of the hip. PMID- 8356741 TI - Indirect immunofluorescence used as confirmatory test for HIV-2 infection in developing countries. PMID- 8356742 TI - The value of family planning user profiles in better targeting of family planning: the case of Vanuatu. PMID- 8356743 TI - The use of filter paper in sero-epidemiological studies: a community based approach. PMID- 8356744 TI - TB control and HIV. PMID- 8356745 TI - Leper--what's in a name? PMID- 8356746 TI - Chloroquine. PMID- 8356747 TI - Ultrasonography in biliary ascariasis. PMID- 8356748 TI - Late presentation of vulval carcinoma in Trinidad. PMID- 8356749 TI - Surgical complications of typhoid fever. PMID- 8356750 TI - The abdominal cocoon. PMID- 8356751 TI - Primary mycetoma of the calcaneum. PMID- 8356753 TI - Spontaneous delivery of the placenta before the fetus in uterine rupture. PMID- 8356752 TI - Amoebic splenic abscess. PMID- 8356754 TI - Venous air embolism: another cause. PMID- 8356755 TI - Bird-related eye injuries. PMID- 8356756 TI - Use of intravenous infusion set tubing for puncture suprapubic cystostomy. PMID- 8356757 TI - Management of tuberculosis. PMID- 8356758 TI - Osteomyelitis in Uganda. PMID- 8356759 TI - Teaching through games. PMID- 8356760 TI - Mothers monitor growth. PMID- 8356761 TI - [Psychopharmacological therapy]. PMID- 8356762 TI - [The effect of serum monitoring on concentration of perphenazine and zuclopenthixole]. AB - The effect of therapeutic drug monitoring (TDM), including pharmacokinetic guidance, was examined in 994 psychiatric patients treated with perphenazine (Trilafon) or zuclopentixol (Cisordinol). Before monitoring of the serum level, half of the serum concentrations from patients given perphenazine tablets (466 patients) was below the therapeutic level, and about one third was above. For perphenazine depot (208 patients), almost no patients had a serum concentration below the therapeutic level whereas 40% had concentrations above. For zuclopentixol tablets (231 patienter) and zuclopentixol depot (163 patients), about 60% of the patients had concentrations above the therapeutic level. For all four groups, it was found that slightly more than half of the patients with serum concentrations outside the therapeutic level was reexamined. The dosage was changed in most of these patients (80-90%) in order to bring the concentration within the therapeutic level. Half of those in whom the dose was changed obtained concentrations within the therapeutic level. It is concluded that since the recommendations for changes of the dosage is followed to a wide extent, the therapeutic drug monitoring service does influence the treatment significantly. PMID- 8356763 TI - [Vaginal bleeding in the first trimester]. AB - Significant changes in attitudes towards patients with vaginal bleeding during the first trimester of pregnancy are taking place at the moment, and it is with this in mind that the relevant literature dealing with these patients is reviewed. The rate of miscarriage in an asymptomatic population of pregnant women is 2-4%. If vaginal bleeding occurs, about half the fetuses will have no detectable heartbeat by the time symptoms appear and miscarriage is taking place. Of the remainder, where heartbeat is demonstrated, only ten percent will miscarry despite the bleeding. The presence of an intrauterine haematoma will at most have marginal significance for the prognosis. There is no treatment that has a documented effect amongst these patients, which is why hospitalization can no longer be recommended. A possible investigational program is suggested. PMID- 8356764 TI - [Pouchitis: acute inflammation in the pelvic ileal reservoir. Diagnostic criteria, frequency, possible etiological factors and treatment]. AB - Pouchitis is a significant long-term complication of restorative proctocolectomy. Pouchitis is characterized by diarrhoea, fever, malaise, abdominal pain and in few a patients a worsening of already present extraintestinal manifestations may occur. The estimated probability of pouchitis occurring within five years is approximately 35%. Standard diagnostic criteria have not yet been established, but clinical symptoms, endoscopic and histological features should be included. The cause of pouchitis is unknown, bacterial over-growth, faecal stasis, oxygen free radicals, secondary and deconjugated bile acids, shortchain fatty acids, gastrointestinal hormones and an immunologically-mediated reaction have all been suggested as possible etiological factors. Metronidazole is the most commonly used treatment and has prompt effect in more than 90% of the patients. Steroids and 5-aminosalicylic acid derivatives also seem to be effective. A diverting ileostomy is necessary in only five to seven percent of the patients, and in less than one percent does pouchitis result in excision of the pouch. Controlled trials with uniform diagnostic criteria are required to assess the effectiveness of the individual regimens. PMID- 8356765 TI - [Parenchymal surgery in patients aged 80 and over--a coming crisis? An analysis of current status and results and an attempt to illuminate future needs]. AB - This study reviews 594 admissions of 434 patients aged 80 years or more to the departments of general surgery in Ringkobing County, Denmark, during one year. Half of the patients were admitted as emergencies, and 60% underwent surgery. The overall mortality was 9%, the postoperative mortality 8%. The number of postoperative complications and the postoperative mortality rate increased in emergency cases and in patients with complicating medical diseases. 72% of all admissions were uncomplicated and 69% of the patients were discharged directly home. Generally, these patients do not block beds, but are discharged as soon as medical care is no longer indicated. During this decade it is expected that the number of admissions of patients aged 80 years or older will increase by about 25%, and unless additional resources are provided, new standards must be considered for the distribution of resources and of indications for surgery in both young and old. Also, the development of less traumatic methods of operative surgery with lower morbidity rates, earlier recovery and reduced hospital stay must be encouraged. PMID- 8356766 TI - [Surgical treatment of hydronephrosis. Late results after surgery using the Anderson-Hynes method]. AB - Twenty-one patients with hydronephrosis mean age 37 years (11-72) were operated using Anderson-Hynes pyeloplasty, without routine use of a nephrostomy catheter. One patient developed urinary leakage postoperatively, which ceased after insertion of a ureteric catheter. Follow-up assessment was performed after a mean observation time of 85 months (44-142). Clinical examination, laboratory investigations, urography and renography were performed preoperatively and at follow-up. No signs of stones or stenosis in the pelvis were found. The patients operated upon before the age of 30 showed improved postoperative renal function. All patients had symptoms preoperatively, but only one had symptoms postoperatively. It can be concluded that the results of surgical intervention in hydronephrosis are excellent, especially in patients below 30 years. PMID- 8356767 TI - [Unrecognized Hodgkin's disease as cause of death. A review of 27 cases diagnosed post mortem]. AB - The purpose of the study was to examine the incidence of unrecognised Hodgkin's disease (HD) as cause of death and to search for clinical features that could have ensured a correct pre-mortem diagnosis. A review of cases of HD reported to the Danish Cancer Registry from 1976 through 1987 in patients younger than 70 years old disclosed 27 where HD was the primary cause of death and the diagnosis was unrecognised at the time of death. The majority of the patients had no concurrent diseases and may have benefitted from a correct diagnosis and a potentially curative treatment. Most of the patients had persistent unexplained fever and weight loss. Pancytopenia, hepatic involvement, bone marrow involvement, advanced stage disease, and lymphocytic depletion histology were also frequent findings. Peripheral or retroperitoneal lymphadenopathy was noted in nine patients without biopsy. The many uncommon features of HD together with the frequent findings of falsely negative chest X-ray, bone marrow examination, liver biopsy, and abdominal ultrasound contributed to the difficulty in diagnosis. However, in about 1/3 of the patients clinical findings suggestive of lymphoma did not result in relevant diagnostic procedures. PMID- 8356768 TI - [Fatal poisonings in Jutland 1980-1989]. AB - A description is given of trends in the pattern of fatal poisonings examined at the Department of Forensic Medicine, Aarhus University during the period 1980 through 1989 (638 men and 391 women). These cases comprised 36% of all fatal poisonings in the area during the decade. In more than half of the medicolegally examined cases, death was categorized as accident. In two thirds of the examined cases death was caused by drugs, whereas non-medical substances (alcohol, carbon monoxide etc.) accounted for one third of the deaths. During the ten-year period, a decline was seen in the number of barbiturate-related deaths, whereas the number of deaths caused by analgesics increased. Propoxyphene was the drug found to have caused most deaths during the period, and developments concerning fatal poisonings involving this drug must still be watched closely. PMID- 8356769 TI - [Penetration of a sliding screw into the pelvis. A rare complication in osteosynthesis of hip fractures]. AB - Penetration into the pelvis by a sliding screw, with screwplate disengagement, is a rare complication after osteosynthesis of intertrochanteric fractures of the femur. This case highlights such an unusual event with fatal outcome. Unstable fracture, osteoporosis, and full weight bearing combined with the failure of the screw to slide within the barrel of the plate and with the absence of a compression screw increases the risk of complications. Optimal reposition and screw placement with a high plate angle, full screw-plate engagement and use of the compression screw is recommendable in unstable fractures. PMID- 8356770 TI - [Injuries of the hand caused by high-pressure air]. AB - Based on two cases of accidental high-pressure air injection injury to the hand, we describe pathology, symptoms and therapeutic principles. Despite nontoxicity of injected air, the importance of acute surgical intervention must be emphasized, as there is a risk of high-pressure soft tissue damage. The treatment suggested is: 1) systemic medication including tetanus toxoid and antibiotics, 2) adequate incision, decompression, exploration, drainage and debridement under either general, plexus or i.v. anaesthesia. Postoperatively, the hand should be elevated, and a program of physical mobilisation should be started as soon as possible. PMID- 8356771 TI - [Infarct of the tongue and hyperlipidemia]. AB - We describe a case of a 49 year-old woman, predisposed to arteriosclerosis, who developed and infarct of the tongue caused by hyperlipidaemia. Treatment and differential diagnoses, including giant cell arteritis, are discussed. PMID- 8356772 TI - [Primary malignant lymphoma in the appendix vermiformis]. AB - Primary gastrointestinal lymphoma (PGL) is a rare condition. A case story concerning a 17 year old boy is presented and discussed. The symptoms were fever and pain in the lower right quadrant of the abdomen, where a tender tumor was palpable. The tentative diagnosis was periappendicular abscess and the patient was treated with antibiotics. As the tumor persisted, a laparotomy with resection of the coecum was performed. Histologic diagnosis was malignant lymphoma originating in the appendix. There was no sign of dissemination in the abdomen. Postoperative treatment with chemotherapy and radiation was carried out. PGL in the appendix in young patients, almost entirely males, will as here often be of the Burkitt type. The histologic type of the tumor, the staging and the radicality at operation are important with regard to prognosis. PMID- 8356774 TI - [On paternalistic cancer science]. PMID- 8356773 TI - [Chordoma localized in the spine]. PMID- 8356775 TI - Applications of a post-column imaging filter in biology and materials science. AB - We have developed an energy-selecting imaging filter which can be attached to most transmission electron microscopes, and is capable of operating at primary energies of up to 400 keV. We review the filter's design and operation, and illustrate them with several applications including imaging of thick biological materials, energy-filtered diffraction, energy-filtered high-resolution imaging, and elemental mapping. We conclude the paper with a discussion of the areas of transmission electron microscopy in which the filter is likely to make especially significant contributions. PMID- 8356776 TI - The present status of ultrasonic imaging in medicine. AB - The ultrasonic techniques that are used routinely in medical imaging have resulted from basic scientific discoveries, new methods of signal analysis and image processing, the development of transducer materials and fabrication techniques, and the application of digital electronics. The system designer is constrained by the ultrasonic properties of tissues, especially speed and attenuation: these properties determine the optimum choices of ultrasonic frequency, and spatial contrast and temporal resolutions. Ultrasonic Doppler techniques provide information about moving targets, including blood flow. Two dimensional images of anatomical structure and blood flow can be combined in real time displays. Other advances include sonoelasticity imaging, computed tomography, three-dimensional imaging, contrast agents and quality assurance. Contemporary ultrasonic diagnostic techniques seem to be safe, but the search for possible hazards is continuing with emphasis on thermal effects and cavitation. PMID- 8356777 TI - Recent activity in ultrasonic tomography. AB - During the past two decades there have been significant developments in many aspects of acoustical imaging techniques for various applications. One aspect of this development has been the application of ultrasonic tomography to medical imaging and diagnosis instrumentation, and also to non-destructive evaluation of materials, to oceanographic systems for measurements of such factors as temperature and currents etc, and to seismic exploration. This paper reviews the theoretical and practical work in acoustical tomography to the present time. PMID- 8356778 TI - Doppler colour flow mapping of fetal intracerebral arteries in the presence of central nervous system anomalies. AB - The adjunctive role of Doppler colour flow mapping in the evaluation of intracerebral morphology and arterial blood flow in the presence of normal and abnormal central nervous system morphology was determined. A total of 59 fetuses with suspected central nervous system pathology between 14 and 37 weeks of gestation was studied (median 31 weeks). One hundred and one fetuses with normal central nervous system anatomy between 14 and 37 weeks (median 19 weeks) served as controls. Visualisation of blood flow in one or more intracerebral arterial vessels was successful in more than 80% of normal fetuses. For the anterior, middle and posterior cerebral artery, the percentages were 63%, 89% and 45%, respectively, at 14-25 weeks and 74%, 100% and 55%, respectively, at 26-37 weeks of gestation. Intracerebral arterial flow identification was attempted in 52/59 (88%) affected fetuses. Identification of blood flow in one or more intracerebral arterial vessels was successful in 40/52 (77%) fetuses. End-diastolic flow velocities were present in at least one of the intracerebral arteries in 39/40 fetuses, absent in one case of hydrocephaly and raised in the presence of an intracerebral vascular tumour. Doppler colour flow mapping seems to provide only limited additional information on intracranial structural pathology. PMID- 8356779 TI - Nonlinear propagation in Doppler ultrasound. AB - The nonlinear propagation of ultrasound was demonstrated using Doppler transducers on two commercial duplex machines. The influence of nonlinear propagation on Doppler measurements was studied on both a flow phantom and a string phantom. It was found that although the pulse waveforms showed clearly different degrees of nonlinear distortion, no effect due to the nonlinearity could be detected on the received Doppler spectrum both in terms of the maximum frequency or underlying Doppler spectral profile. PMID- 8356780 TI - Quantification of ventricular remodeling in the tight-skin mouse cardiomyopathy with acoustic microscopy. AB - To determine the role of ultrasonic tissue characterization for the detection of changes in myocardial architecture associated with cardiomyopathy, acoustic microscopy was performed on the hearts of 4- to 6-month-old tight-skin mice [TSK/+, C57-B10.D2 (58B)/SN strain], a model of cardiomyopathy characterized by diffuse interstitial fibrosis. Ultrasonic backscatter was measured from excised segments of left ventricular free walls of five TSK mice and five sex- and age matched normal controls with a 50 MHz broad band focused piezoelectric transducer operated in a saline-filled water tank at room temperature. Forty-nine radio frequency (RF) lines were digitized from each specimen at 2 ns/sample. Power spectral analysis of RF data was performed and mean integrated backscatter (IB) computed. The TSK group demonstrated greater IB (-53.6 +/- 0.6 dB, n = 5) than did the control group (-56.6 +/- 0.7 dB, n = 5; p < 0.02). Myocardial collagen content determined by hydroxyproline assay increased by 11% in the TSK group (2.54 +/- 0.08 microgram/mg dry wt, n = 5) over that in controls (2.28 +/- 0.07 microgram/mg dry wt, n = 5; p < 0.05). A significant linear relationship was observed between myocardial hydroxyproline concentration and IB (r = 0.74; p < 0.02). Thus, ultrasonic tissue characterization permits sensitive detection of modest changes in the extent of interstitial fibrosis that accompany tissue remodeling in the early stages of cardiomyopathy. PMID- 8356781 TI - In vitro evaluation of gallstone dissolution with methyl-tert-butyl ether and ultrasound energy. AB - Given the large number of cholecystectomies performed annually, a nonsurgical approach to gallstone therapy is of great interest. A laboratory ultrasound system has been developed to study enhancement of methyl-tert-butyl ether (MTBE) dissolution of human gallstones in vitro. A mathematical model that quantitatively characterizes the dissolution process via a rate constant has been developed. Using this model, the kinetics of 15 gallstones from a single patient were evaluated for three dissolution methods: 1) unstirred MTBE, 2) aspirated MTBE, and 3) ultrasonically enhanced MTBE. The results showed excellent fits between the model and measured dissolution rates. 195 kHz continuous-wave (CW) ultrasonically enhanced dissolution rates exhibited a 6.2 fold gain over the manually aspirated MTBE and a 49.5 fold gain over static MTBE dissolution. Investigation of 50% duty cycle pulsed mode ultrasound revealed that total power appears to be the determinant of the observed dissolution rates. Gallstone calcification showed a strong correlation with dissolution rates measured by the model. PMID- 8356782 TI - Effects of pulsed ultrasound on the frog heart: I. Thresholds for changes in cardiac rhythm and aortic pressure. AB - High intensity pulsed ultrasound at 1.2 MHz is shown to change the cardiac rhythm and aortic pressure of frog hearts in vivo. Threshold levels for these effects occur at acoustic pressure amplitudes of the order of 10 MPa for 5 ms pulse lengths. Depending upon the phase of the heart cycle, a pulse of ultrasound either may cause a premature ventricular contraction, a reduction in the strength of contraction as measured by the aortic pressure, or an enhanced relaxation of the heart muscle. There is an increase in the effectiveness of the ultrasound with increase in pulse length in the range from 1 to 5 ms. PMID- 8356783 TI - Effects of pulsed ultrasound on the frog heart: II. An investigation of heating as a potential mechanism. AB - This study investigated heating as the possible mechanism for the reduction in aortic pressure observed as a result of exposure of frog hearts in vivo to a single, high intensity pulse of ultrasound. The threshold for producing reduced aortic pressure with 5 ms pulses of ultrasound was found to be approximately 5-10 MPa peak positive pressure (ISPPA approximately 350-1000 W/cm2) at both 1.2 MHz and 3.7 MHz. Theoretical estimates and experimental measurements of heating, though, indicate that heating rates at threshold exposures for these two frequencies differ by as much as a factor of 10. As a result, heat alone does not appear to be the primary mechanism responsible for the observed effects on the heart. PMID- 8356784 TI - Biological effects of high energy shock waves in mouse skeletal muscle: correlation between 31P magnetic resonance spectroscopic and microscopic alterations. AB - To investigate the in vivo effects of electromagnetically generated high energy shock waves (HESW) on skeletal muscle, we used in vivo 31P nuclear magnetic resonance (NMR) spectroscopy (MRS) measurements and correlated the results with microscopical studies. Mouse skeletal muscle (calf muscle) was exposed to 200 or 800 HESW (Pmax: 37.5 MPa, Pmin: 5.2 MPa, tr: 30-120 ns, tw: 340 ns, frequency: 1.25 Hz). In the 31P MRS spectra, transient alterations were observed. A prominent increase of inorganic phosphate (Pi) peaks was found, as well as the appearance of Pi with different chemical shifts, reflecting the presence of different pH values (5.4-7.1) in cellular or tissue compartments. Within 20-96 h after exposure, pH values and Pi levels returned to normal. The changes were more pronounced in the animals treated with 800 HESW as compared to 200 HESW. Light and electron microscopy demonstrated focal degenerations of muscle fibers. This process consisted of disorganization of myofilaments and structural changes in sarcoplasmic organelles and was progressive in time. The (ultra)structural changes were not present in all myofibers (i.e., between affected degenerating fibers unaffected intact fibers were seen). Several ultrastructural abnormalities were also found in capillaries even up to severe dilatation and disruption, as well as in the peripheral nerves. The degeneration of the preexisting myofibers was predominantly confined to type 1 fibers and was followed by a regeneration of the muscle tissue by proliferation of myoblasts. A notable amount of myotubes still showed vacuolization. We conclude that in vivo HESW exposure of skeletal muscle tissue results in a degeneration of myofibers. The cellular effects are present in foci and associated with changes in the 31P NMR spectra. The NMR spectroscopy technique provides us with a noninvasive method to evaluate in a longitudinal way the biological effects of HESW. PMID- 8356785 TI - Ultrasound-induced enhancement of ACh, AChE and GABA in fetal brain tissue of mouse. AB - Pregnant mice were exposed to continuous-wave (CW) ultrasound of 875 kHz frequency at 1 W/cm2 for 300 and 400 s, spread over five days, starting from the sixth day of pregnancy. The neurotransmitters, acetylcholine (ACh) and gamma amino butyric acid (GABA), and the associated enzyme acetylcholinesterase (AChE) levels, were estimated in the exposed fetal brains. Enhanced levels, significant at p < 0.001, were observed in the brains excised on day 10, day 15 and day 20 of gestation compared to sham-exposed and cage-control brains. PMID- 8356786 TI - Heating of guinea-pig fetal brain during exposure to pulsed ultrasound. AB - Ultrasound-induced temperature elevations in fresh and formalin-fixed fetal guinea-pig brains were measured during in vitro insonation, with a stationary beam in a tank containing water at 38 degrees C. The pulsing regimen used 6.25 microseconds pulses, repeated at a frequency of 4 kHz emitted from a focussed transducer operating with a centre frequency of 3.2 MHz. The greatest temperature rise in brain tissue occurred close to bone and correlated with both gestational age and progression in bone development. After a 2 min insonation with a spatial peak temporal average intensity (ISPTA) of 2.9 W/cm2, a mean temperature elevation of 5.2 degrees C was recorded in fetuses of 60 days gestation (dg). The same exposure produced an increase of 2.6 degrees C in the centre of whole brains of 60 dg fetuses when the bony cranium was removed. As most of the heating occurs within 40 s, these findings have implications for the safety of pulsed Doppler examinations where dwell-time may be an important factor. PMID- 8356787 TI - Mutations in the transmembrane domain of the HN protein of Newcastle disease virus affect the structure and activity of the protein. AB - To explore the role of the transmembrane domain of the HN protein in the structure and function of the molecule, three conserved leucine residues in this domain which occur in a heptad-repeat motif were changed to alanine singly or in combination by site-specific mutagenesis. None of the mutant proteins were defective in translocation and intracellular transport. All mutant proteins formed disulfide-linked dimers. However, tetrameric structures of proteins with mutations in the third or most carboxy-terminal leucine could not be detected by sucrose gradient analysis, and mutant proteins with changes in both the first and second leucine formed less-stable tetramers. These results suggest that the transmembrane domain plays a role in the tetrameric structure of the HN protein. These mutations also altered the biological activities of the protein. Mutant proteins with alterations in the third leucine were very defective in attachment activity and somewhat defective for neuraminidase activity while all other mutant proteins had wild-type levels of attachment and neuraminidase activity. While all mutant proteins showed diminished fusion-promotion activity, proteins with mutations in the third leucine and proteins with changes in both the first and second leucines were very defective in fusion promotion. These results suggest that elimination or destabilization of the tetrameric structure affects attachment activity and fusion-promotion activity of the HN protein. PMID- 8356788 TI - Probing of the receptor-binding sites of the H1 and H3 influenza A and influenza B virus hemagglutinins by synthetic and natural sialosides. AB - To compare features of the receptor-binding sites (RBSs) of different influenza virus hemagglutinins (HA), binding of a number of synthetic sialic acid (SA) analogs and natural sialosides by a panel of about 30 human influenza A and B virus strains was studied in a competitive ligand binding assay. For all the viruses tested, the N-acetyl group of Neu5Ac, as well as the natural orientation of the carboxylic group at C2 and the hydroxylic group at C4, was essential for binding. Significant type- and subtype-specific differences were observed in virus recognition of asialic parts of sialosides. H1 strains, unlike H3 and type B viruses, were found to bind alpha 2-6-sialyl-N-acetyllactosamine with about an order of magnitude higher affinity than alpha 2-6-sialyllactose (6'SL). The H1 viruses and the H3 strains with Gln in position 226 of HA, but not the H3 strains with Leu-226, bound 6'SL with a lower affinity than alpha 2-3-sialyllactose; this effect correlated clearly with the preferential binding by the former viruses of unsubstituted alpha Neu5Ac compared to methyl alpha-glycoside of Neu5Ac. Thus, differentiation between the types of the SA-Gal linkage by the A viruses appeared to depend, at least partially, upon the recognition by the HA of the first hydrocarbon group of the aglycon. Type B virus strains were distinct in having a lower affinity for the Neu5Ac moiety and in providing a higher contribution of the asialic portions of sialosides to the HA-ligand interactions. The last effects are presumably due to the amino acid insertions in the type B HA surrounding the RBS, which makes the receptor-binding pocket deeper. The results obtained in the present investigation indicate that while the functional groups of Neu5Ac studied are recognized by the RBSs of all influenza viruses, the magnitude of their contribution to the binding energy, as well as the contribution of the asialic portion of the receptor, may vary in dependence upon the virus type, subtype, and strain. PMID- 8356789 TI - Regulation of HIV-1 envelope protein synthesis by Tat and Rev in 293 cells. AB - A plasmid expression vector (B2) with the HIV-1 envelope sequence downstream of the adenovirus type 5 early region 3 promoter could direct the synthesis of envelope protein in the absence of Rev when transfected into 293 cells. We investigated this further using pNL4.3 delta TR, and HIV-1 mutant which lacks the first exon of Tat and Rev and pNL4.3 delta R, an HIV-1 mutant with a premature termination codon in the second coding exon of Rev. In cells transfected with pNL4.3 delta TR and a Tat-expressing vector or with pNL4.3 delta R alone, analysis of RNA revealed the accumulation of cytoplasmic Env mRNA in the absence of Rev. However, envelope protein synthesis was observed in the absence of Rev only in cells transfected with pNL4.3 delta TR and a Tat-expressing vector, not in cells transfected with pNL4.3 delta R. The Env mRNAs synthesized from pNL4.3 delta R can have 536 to 548 nucleotides of 5' non coding sequence, whereas the Env mRNA from pNL4.3 delta TR will have a shortened noncoding sequence of 321 nucleotides. These results indicate that the mRNA sequences 5' to the Env protein initiation codon have a role in Env expression. PMID- 8356790 TI - Influence of host cell-mediated variation on the international surveillance of influenza A (H3N2) viruses. AB - Growth of clinical specimens of influenza viruses in eggs can result in the selection of antigenic variants distinct from corresponding viruses grown in mammalian tissue culture. To evaluate the contribution of host cell selection on the antigenic diversity of human influenza isolates, as seen in annual surveillance studies, viruses grown in embryonated eggs were compared by antigenic and genetic analyses with their mammalian tissue culture-grown counterparts. Clinical specimens were gathered from around the world from late 1987 to 1990 and the antigenicity of isolated viruses was assessed by hemagglutination-inhibition assays using immune ferret sera as is currently performed for routine surveillance and the selection of vaccine strains. In addition, viruses were assessed using a panel of anti-H3 HA monoclonal antibodies. The extent of antigenic variation exhibited by the egg-grown strains was far greater than the relative antigenic homogeneity of the tissue culture grown viruses. Nucleotide sequence analysis of HA1 gene PCR products of 28 MDCK cell and egg derived pairs allowed identification of amino acid substitutions responsible for the antigenic differences observed and the adaptation to growth in eggs. Among these substitutions was a change at amino acid position 186 of HA1 (Ser in tissue culture viruses and lle in egg-grown viruses) which was observed at relatively high frequency. Egg- and MDCK-grown pairs with this single amino acid difference were classified into distinct antigenic groups by ferret sera raised to WHO reference viruses. Given the additional antigenic diversity observed among egg-grown strains, considerable care should be taken in the selection of reference and vaccine strains grown in eggs. Rapid sequence comparisons of MDCK- and egg-grown viruses allow identification of variants arising through egg selection and will prove to be a useful adjunct to antigenic surveillance for the selection of reference and vaccine strains. PMID- 8356791 TI - Comparison of envelope and precore/core variants of hepatitis B virus (HBV) during chronic HBV infection. AB - We analyzed entire pre-C/C and pre-S/S coding genes of hepatitis B virus (HBV) in serial serum samples from four chronic HBV carriers with 4-5 years of follow-up. Two patients with chronic active hepatitis became seronegative for HB e antigen (HBeAg), but the hepatitis did not subside, while the other two were persistent asymptomatic carriers with normal aminotransferase values. DNAs amplified by PCR were cloned and sequenced (subtype adr). After HBeAg became negative, one patient had 96-183 bp deletions in 4/6 clones for C gene. In addition, both patients had 129-183 bp deletions in 3/6 and 2/5 clones for pre-S1 gene, respectively. Divergence rate of deduced amino acid for both pre-C/C and pre-S/S regions from the adr subtype was significantly higher in patients with chronic hepatitis than in asymptomatic carriers. Furthermore, the divergence rate for pre-S/S region was usually greater in asymptomatic carriers as well as chronic hepatitis patients compared with that for pre-C/C region. However, no significant difference was found in the rate of amino acid divergence for the entire HBV genes between the serial samples in all patients studied here. These results suggest that active hepatitis induces variation of HBV gene and defective virus is often selected along with the disappearance of HBeAg. In addition, the fact that patients with active liver disease possess greater numbers of mutant clones than asymptomatic carriers suggests that viral mutants are being immune-selected. PMID- 8356792 TI - HTLV-1 gene expression by defective proviruses in an infected T-cell line. AB - We have examined human T-lymphotropic virus type I (HTLV-I) gene expression in the human T-cell line, C8166-45 (C81), as a model to define the gene products expressed from defective proviruses. C81 cells contain one complete and two different deleted proviral genomes. The internal deletions of the latter encompass most of the gag to env region. All three proviruses are transcriptionally active as evidenced by the presence of three unspliced nuclear mRNAs. Unspliced genomic mRNAs and singly spliced env mRNAs were present in the nucleus, but were not detected in the cytoplasm, suggesting a defect in Rex function. Three small cytoplasmic mRNAs were observed and are likely to correspond to the normal 1.8-kb Tax1/Rex1 mRNA, a 1.6-kb mRNA formed by splicing the 5'LTR to the pX region, and a 2.1-kb mRNA of unknown origin. Consistent with the subcellular mRNA distribution pattern, the viral structural proteins encoded by gag and env genes were not detected. The transcriptional transactivator protein, Tax1 (p40), was abundantly expressed in C81 cells; in addition, a 42-kDa Tax1 protein, unique to this cell line, was also detected. Although Tax1 and Rex1 (p27) are translated from overlapping open reading frames in the same mRNA, Rex1 was not detected in C81 cells. The presence of a premature termination codon in the Tax1/Rex1 mRNA encoded by the full-length provirus was inferred from the presence of small Rex1-related polypeptides lacking C-terminal sequences and confirmed by sequence analysis. Furthermore, a p21X protein lacking the N terminus of Rex1 was expressed at high levels; our data indicate that p21X is translated from the 1.6-kb mRNA which is derived primarily from deleted proviruses. PMID- 8356793 TI - Leader-mRNA junction sequences are unique for each subgenomic mRNA species in the bovine coronavirus and remain so throughout persistent infection. AB - The common leader sequence on bovine coronavirus subgenomic mRNAs and genome was determined. To examine leader-mRNA junction sequences on subgenomic mRNAs, specific oligodeoxynucleotide sets were used in a polymerase chain reaction to amplify junction sequences from either the positive-strand mRNA (eight of nine total identified species) or the negative-strand anti-mRNA (six of the nine species), and sequenced. The mRNA species studied were those for the N, M, S, and HE structural proteins and the 9.5-, 12.7-, 4.8-, and 4.9-kDa putative nonstructural proteins. By defining the leader-mRNA junction sequence as the sequence between (i) the point of mismatch between the leader and genome and (ii) the 3' end of the consensus heptameric intergenic sequence [(U/A)C(U/C)AAAC)], or its variant, a unique junction sequence was found for each subgenomic mRNA species studied. In one instance (mRNA for the 12.7-kDa protein) the predicted intergenic sequence UCCAAAC was not part of the junction region, and in its place was the nonconforming sequence GGTAGAC that occurs just 15 nt downstream in the genome. Leader-mRNA junction sequences found after 296 days of persistent infection were the same as those found during acute infection (< 18 hr postinfection). These data indicate that, in contrast to the closely related mouse hepatitis virus, the bovine coronavirus maintains a stable leader-mRNA junction sequence for each mRNA. Interestingly, this stability may be related to the fact that a UCUAA sequence element, postulated by others to be a regulator of the leader-mRNA fusion event, occurs only once within the 3' flanking sequence of the genomic leader donor and once at intergenic sites in the bovine coronavirus genome, whereas it occurs two to four times at these sites in the mouse hepatitis coronavirus. PMID- 8356794 TI - Differences between cell membrane fusion activities of two dengue type-1 isolates reflect modifications of viral structure. AB - The genetic diversity of dengue (DEN) virus was explored using two South American DEN-1 virus strains isolated from viremic human sera. DEN-1 virus strains BR/90 and FGA/89 were selected on the basis of their membrane fusion properties in mosquito cell cultures. Infection of mosquito cell lines with BR/90 virus strain induced a cytopathic effect characterized by syncytium formation whereas no cytopathic changes were observed with FGA/89. Cell-to-cell fusion experiments indicated that the fusogenic activity of FGA/89 required a lower pH than BR/90. Immunoreactivity analysis of the DEN-1 envelope (E) protein with monoclonal antibodies revealed a minor difference between the antigenic structures of FGA/89 and BR/90 virions. FGA/89 was less neurovirulent than BR/90 for newborn mouse. To determine the genetic origin of these modifications, the amino acid sequences of the structural proteins from these virus strains were compared. One amino acid difference was found within the carboxy-terminal domain of protein C. Five amino acid substitutions were found in the E proteins at positions 96, 180, 297, 379, and 473. Changes at positions 96, 297, and 379 map within two overlapping antigenic domains of protein E. These limited amino acid differences in the E protein could affect the biological properties and the antigenicity of the DEN virion. PMID- 8356795 TI - Attachment of the gammaherpesvirus bovine herpesvirus 4 is mediated by the interaction of gp8 glycoprotein with heparinlike moieties on the cell surface. AB - Cell surface heparan sulfate serves as the initial receptor for several alphaherpesviruses and at least one betaherpesvirus. This study shows that during the process of adsorption of the gammaherpesvirus bovine herpesvirus 4 (BHV-4), the viral glycoprotein gp8 interacts with heparinlike moieties of cell surface. This conclusion is based on the following findings. (i) Soluble heparin was capable of blocking BHV-4 infection of Georgia bovine kidney cells by inhibition of viral attachment. (ii) Nevertheless, after virus adsorption to Georgia bovine kidney cells, heparin was partially capable of removing adsorbed virus. (iii) Enzymatic digestion of cell surface heparan sulfate but not of chondroitin sulfates A, B, and C reduced the binding of the virus to the cells, and rendered the cells partially resistant to infection. (iv) Radiolabeled purified BHV-4 bound to wild-type Chinese hamster ovary cells, whereas binding of the virus to mutant Chinese hamster ovary cell lines that where deficient in either all glycosaminoglycans or only heparan sulfate was significantly impaired. (v) Using heparin-affinity chromatography, gp8 glycoprotein was shown to bind specifically to immobilized heparin and to elute in the presence of soluble heparin. These data together showed that the gammaherpesvirus BHV-4, like alphaherpesviruses and one betaherpesvirus, adsorbs to cells by binding to cell surface heparin-like moieties. Therefore, this study extends the group of herpesviruses interacting with heparinlike moieties at the cell surface to a member of the gammaherpesvirinae subfamily. PMID- 8356796 TI - Molecular assembly of influenza virus: association of the NS2 protein with virion matrix. AB - The NS2 protein, one of the two nonstructural proteins of influenza A virus, was found to exist in virus particles. By immunochemical method, the average number of NS2 in a virus particle was estimated to be 130-200 molecules. After solubilization of viral envelope, NS2 was still associated with ribonucleoprotein cores, but was later dissociated upon removal of the M1 protein. A filter-binding assay in vitro indicated direct protein-protein contact between M1 and NS2. Following chemical cleavage of the M1 protein, NS2 bound only a C-terminal fragment of M1. By immunoprecipitation, NS2-M1 complexes were also detected in virus-infected cell lysates. These observations altogether indicate specific molecular association between M1 and NS2. Biological significance of M1-NS2 interaction is discussed. PMID- 8356797 TI - In vivo infection of human T-cell leukemia virus type I in non-T cells. AB - Using three different procedures, immunomagnetic isolation, FACS and panning, each of the T4 cell, T8 cell, monocyte, and B cell population was fractionated from peripheral blood mononuclear cells (PBMC) obtained from 10 human T cell leukemia virus type I (HTLV-I)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) cases, 3 adult T cell leukemia and lymphoma (ATLL) cases and 9 HTLV-I-infected healthy carriers. DNA from each fraction was then subjected to the quantitative polymerase chain reaction. Although T4 cells possessed the highest copy number of HTLV-I in general, we also detected a significant amount of HTLV-I provirus in T8 cells, monocytes, and B cells. To confirm virus infection of the non-T cell populations, especially the monocyte fraction, we performed further experiments and the following results were obtained: (1) HTLV-I tax RNA expression was confirmed simultaneously in the RNA of monocytes that were negative for T cell receptor beta chain (TCR beta) expression in vivo. (2) We cultured these monocytes for a short period of time and detected HTLV-I antigen expression in non-specific esterase-positive monocyte/macrophage cells. Our data indicate that HTLV-I has a broad host range in vivo and that monocytes or cells of monocyte lineage such as tissue macrophages might comprise a virus reservoir in vivo. PMID- 8356798 TI - BEL-1 transactivator responsive sequences in the long terminal repeat of human foamy virus. AB - Cis-regulatory elements in the long terminal repeat (LTR) of human foamy virus (HFV) were identified by using LTR mutants to transiently express the chloramphenicol acetyl-transferase gene after co-transfection with an expression plasmid for the virus bel-1 (transactivator) gene. The R-U5 region and an element in the 5' U3 region were found to negatively influence HFV gene expression. The complete BEL-1 responsive region was mapped to extend from nucleotide position 471 to position -93 relative to the start of transcription. Within this region, three elements were identified that in the homologous or a heterologous (SV40) promoter context can, independently and irrespective of their orientation, act as targets for BEL-1. These elements are located between nucleotide positions -413/ 378, -361/-291, and -124/93. The target elements do not share obvious sequence homologies. The mechanism of HFV transactivation appears to be novel among the complex retroviruses and is likely to involve, as yet, undiscovered cellular DNA binding factors. PMID- 8356799 TI - Multiple functions of the adenovirus DNA-binding protein are required for efficient viral DNA synthesis. AB - Mutational analysis within the amino-terminal (N-t) domain of the adenovirus DNA binding protein (DBP) defined a region (aa 2-38) important for DBP function. Several viruses carrying lesions in this region of DBP showed reduced accumulation of viral DNA and infectious virions. Characterization of one of these mutants, H5in800, indicated that the N-t domain affects viral DNA synthesis in vivo. The reduction in DNA synthesis was not due to a change in the amount or nuclear location of the H5in800 DBP. Expression of other early genes in H5in800 infected cells was similar to that seen in wild-type Ad5-infected cells, suggesting that the depression of DNA synthesis was not due to disruption of DBP's role in early gene expression. The H5in800 and wild-type DBP also had comparable affinities for single-stranded DNA and functioned with similar efficiencies in two DNA elongation assays. Prior studies have shown that the carboxyl-terminal (C-t) domain of DBP was responsible for these two activities. Together these results suggest that DBP has at least two separable functions in viral DNA replication in vivo and that both domains of the protein are necessary for full activity. The intragenic complementation between the N-t mutant H5in800 and the C-t mutant H5in804 supports this model. PMID- 8356800 TI - The direction and rate of bacteriophage T7 DNA packaging in vitro. AB - To determine the direction of the entry of DNA during in vitro bacteriophage T7 DNA packaging, incompletely packaged DNA (ipDNA) was fractionated by agarose gel electrophoresis after degradation of DNA outside of capsids and then release of packaged DNA from capsids. After fractionation, quantitative in-gel probing with a right end-specific oligonucleotide detects heterogeneous ipDNA (called right end ipDNA). Most of the right-end ipDNA appears with kinetics expected of a precursor to the mature T7 DNA. In-gel probing with a left-end-specific oligonucleotide detects ipDNA (left-end ipDNA); the molar amount of left end ipDNA is always at least 50x less than the molar amount of right-end ipDNA. Left end ipDNA appears with the kinetics of an abortive end product of T7 DNA packaging. Thus, productive T7 DNA packaging occurs in a right-to-left direction. Quantitation of the conversion of right-end ipDNA to mature-length DNA yields an estimate of the mean rate of right-to-left in vitro T7 DNA packaging: 28 +/- 6 kbp/min for the last 20-50% of the DNA packaged. PMID- 8356802 TI - Crystallization and preliminary X-ray characterization of tobacco streak virus and a proteolytically modified form of the capsid protein. AB - Isolated tobacco streak virus strain mild (TSV-M) top nucleoprotein component (TV) was crystallized by vapor diffusion with polyethylene glycol (PEG) and methyl pentanediol. The morphology of the crystal suggested a hexagonal space group, however, the crystals were disordered as analyzed by X-ray diffraction. Capsid protein from TSV (strains M and white clover) was treated with trypsin to remove 87 amino terminal residues. The modified capsid protein was purified by ion exchange chromatography and crystallized in both hexagonal and triclinic forms. Hexagonal crystals grown by vapor diffusion in PEG diffract X rays to 4.5 A. The crystals, in the space group P6(2) or its enantiomorph, possess unit cell dimensions of a = 98.3 A, c = 108.7 A and probably contain 12 dimers/unit cell. Triclinic crystals grown by vapor diffusion in ammonium sulfate diffracted X rays to 2.4 A resolution when exposed to X-ray synchrotron radiation. The crystals have unit cell dimensions of a = 60.1 A, b = 77.5 A, c = 73.9 A with alpha = 67.8 degrees, beta = 130 degrees, and gamma = 106 degrees and probably contain 4 dimers/unit cell. PMID- 8356801 TI - A transgenic model of transactivation by the Tax protein of HTLV-I. AB - The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax. PMID- 8356803 TI - An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site. AB - An immune-selected point-mutation (HXB2-Env:Ala582(-->Thr)) in the transmembrane protein, gp41, of the human immunodeficiency virus type 1 confers relative insensitivity to neutralization by a number of sera from HIV-1-positive persons. Affinity-purified human antibodies to continuous epitopes spanning Ala582 do not neutralize the virus (C. Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and M. J. Robert-Guroff, J. Virol. 64, 3240-3248, 1990). The specificity of the antibodies that the mutation renders less active has not previously been determined. We now report that this substitution in gp41 reduces the neutralizing activity of monoclonal antibodies to discontinuous gp120 epitopes, which overlap with the CD4-binding site. There was no such difference in sensitivity to neutralization by soluble CD4, CD4-immunoglobulin, or by two monoclonal antibodies to the V3 region of gp120. Furthermore, the ability of 10 human HIV-1-positive sera to block the binding of soluble CD4 to mammalian recombinant gp120 correlated weakly with their differentiation of neutralization between the wild-type and the Env:Ala582(-->Thr)-mutant virus. We thus suggest that the substitution in gp41 modulates the conformation of gp120 so as to decrease viral sensitivity to one category of antibodies which is partly responsible for the group-specific neutralization of HIV-1 by human sera. PMID- 8356804 TI - Enhanced activity of human G6PD promoter transfected in HeLa cells producing high levels of HIV-1 Tat. AB - Glucose 6-phosphate dehydrogenase (G6PD) enzyme activity has an important role in the cell defence against oxidative damage produced by hydrogen peroxide, a compound known to activate HIV-1 expression through the intermediate of NF-kappa B. By means of CAT assays, in this paper we show that the Tat protein increases the rate of transcription from the human G6PD promoter in HeLa cells; furthermore, we report a similar effect of Tat on transcription driven from the viral RSV promoter. We did not observe Tat stimulation with the human CMV, SV40 or the basic RSV promoters. Dose-response curves indicate that Tat activates G6PD and RSV through a mechanism different from the major one operating on the HIV-1 LTR promoter. TAR-like structures are not involved, instead a short sequence close to the G6PD transcription start site and the RSV LTR enhancer is a good candidate for mediating the phenomena described in this paper. This sequence has some features in common with the NF-kappa B motif. PMID- 8356805 TI - A novel terminase activity associated with the DNA packaging protein gp17 of bacteriophage T4. AB - The mechanism of generation of circularly permuted ends in bacteriophage T4 by a strictly headful packaging process has remained unresolved since its proposal by Streisinger et al. (1967, Proc. Natl. Acad. Sci. USA 57, 292-295). In this paper, we show that the phage T4 DNA packaging proteins gp16 and gp17 act as T4 terminase. Expression of gp16 and gp17 in Escherichia coli resulted in extensive cleavage of both plasmid as well as E. coli genomic DNAs. Analysis of a number of recombinant terminase constructs, and mutants in gene 17, demonstrated that the active site for cleavage of DNA is located in gp17, but not in gp16. Consistent with the circularly permuted nature of phage T4 ends, cleavage by gp17 occurred in a sequence independent manner generating random ends. The terminase cutting occurred preferentially on a DNA substrate that is transcriptionally active. We propose that a structural feature in the transcriptionally active region provides a site for attachment of terminase to DNA following which the terminase moves along the DNA, and cleaves at a random sequence. PMID- 8356806 TI - Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. AB - Human teratocarcinoma-derived viruses (HTDV) are retrovirus-like particles that are regularly observed by electron microscopy at low frequency in cell lines established from human teratocarcinomas. Over the last years, one of our teratocarcinoma cell lines spontaneously began to produce high amounts of HTDV. This cell line is stained in immunofluorescence tests by an antiserum raised against recombinant gag protein of HERV-K, an expressed human endogenous retrovirus sequence. In immunoelectron microscopy of ultrathin frozen sections, this anti HERV-Kgag-specific antiserum reacts specifically with HTDV particles. In Western blots, the antiserum recognizes predominantly a protein with an apparent molecular weight of 30 kDa, presumably the major core protein of HTDV particles. Taken together, these results provide evidence that HERV-K codes for HTDV. PMID- 8356807 TI - Complete nucleotide sequence of HTLV-II isolate NRA: comparison of envelope sequence variation of HTLV-II isolates from U.S. blood donors and U.S. and Italian i.v. drug users. AB - The entire nucleotide sequence of human T-cell lymphotropic virus type II (HTLV II) from a previously described isolate of patient NRA (HTLV-IINRA) was determined. Clones encoding the 5' LTR and gag, pol, env and tax/rex open reading frames were subcloned and sequenced on both strands. The provirus consisted of 8957 nucleotides and showed 95.2% homology with the HTLV-IIMo prototype at the nucleotide level. Less than 5% amino acid variation between HTLV-IINRA and HTLV IIMo was observed for coding regions. Although isolate HTLV-IINRA had an additional 25 amino acids at the 3' end of tax/rex, this region was 96% homologous with the 5' end of HTLV-IIMo 3' LTR. To further investigate HTLV-II variability, a portion of the env gp46 gene derived from 9 HTLV-II infected persons was amplified by polymerase chain reaction and sequenced. Sequence was obtained for 320 nucleotides corresponding to HTLV-IIMo positions 5291 to 5610. Isolates similar to the HTLV-IIMo and HTLV-IINRA prototypes were identified, and sequences were highly conserved. PMID- 8356809 TI - [The optimization of academic classes in military hygiene]. PMID- 8356808 TI - Alterations in cell membrane permeability by the lentivirus lytic peptide (LLP-1) of HIV-1 transmembrane protein. AB - Previously we reported that synthetic peptide homologs of an amphipathic region (designated the lentivirus lytic peptide, or LLP-1) near the carboxy terminus of HIV-1 transmembrane protein (TM) were toxic for both prokaryotic and eukaryotic cells when added exogenously to cell cultures. We postulated that these peptides may exert their toxic effects in much the same manner as natural cytolytic peptides such as magainins, cecropins, and melittin by forming pores through cellular membranes. Here we show the results of 51Cr-release assays and membrane flux measurements of peptide treated cells that support our hypothesis. We have also tested a limited panel of LLP-1 peptide analogs in these assays and found that relatively minor alterations in peptide charge or amphipathicity in the parent HIV LLP-1 sequence resulted in total loss of membrane perturbative properties. These results demonstrate that the peptide homolog of HIV-1 LLP-1 can indeed perturb membranes by forming pores of defined size in cytoplasmic membranes. Furthermore, the analog studies described here reveal that the amphipathy and high positive charge of this protein segment are required for the membrane perturbative properties. PMID- 8356810 TI - [The improvement of independent work--the most important factor in raising quality in the continuing education of physician administrators]. PMID- 8356811 TI - [The work of a medical institute military department under the new socioeconomic conditions]. PMID- 8356812 TI - [The effect of dalargin on the course of combined radiation lesions (experimental research)]. PMID- 8356813 TI - [The use of the helium-neon laser in treating gunshot wounds]. PMID- 8356814 TI - [The expansion of the indications for prescribing laser therapy in chronic recurrent dermatoses]. AB - Besides the well-known methods applied for the treatment of chronic recurrent dermatoses, the authors propose to use laser therapy for management of its coexistent diseases. The article contains data which prove the high efficiency of laser therapy for treatment of chronic recurrent dermatoses with such coexistent diseases as tonsillitis, hymoritis, gastroduodenal erosion, ulcers and respiratory diseases. Methods of laser therapy are enclosed. PMID- 8356815 TI - [Skin diseases and the problems of military medical expertise under the conditions of the Far North]. PMID- 8356816 TI - [The clinico-anatomical characteristics of dermatogenic sepsis in servicemen]. PMID- 8356817 TI - [The effect of hyperbaric oxygenation on hemostasis in the treatment of jaw deformities]. PMID- 8356818 TI - [The laboratory diagnosis of atherogenic disorders in servicemen]. AB - In order to calculate the atherogenic coefficient the authors have made a comparative estimation of methods for determining alfa-cholesterin in serum applying various temperature regimes during sedimentation of beta and pre-beta lipoproteids. It was found out that the complete sedimentation of beta and pre beta-lipoproteids could be obtained after incubation of specimen into the ice bath for 30 min. (t 0-4 degrees C) with further centrifugation at room temperature. No differences were disclosed in comparison with the reference method based on refrigerated centrifugation at 2-4 degrees C. PMID- 8356819 TI - [The prospects for using inactivated influenza vaccines on the troops]. AB - The article analyses the results of controlled epidemiologic observation made in military unit to estimate the immunological and clinico-epidemiological efficiency of national inactivated influenza vaccines with different valency and antigen charge in inoculative dose. The analysis proves the high immunogenic activity and protective features of inactivated influenza trivaccines with enhanced contents of hemagglutinins. The article substantiates the reasons for mass application of these vaccines in military units with obligatory addition of B-component and enhanced antigen contents of vaccine viruses in inoculative dose. PMID- 8356820 TI - [The prospects for the development of the laboratory diagnosis of HIV infection in military medicine]. PMID- 8356821 TI - [The training of military physicians]. AB - The article proposes to regard the training of military physicians as a cybernetic command system with an instructor as a command body, and a student as an object of command. During curriculum planning it is necessary to take into consideration the correlative factors of this system. The analysis of elements which form within students the concept of goal of study has shown that in some cases it was important to make corrections and take into account various motivations. The course of training has a number of new aspects, including computer application, which inevitably need adaptative period. PMID- 8356822 TI - [Solid-phase immunoenzyme analysis in the differential diagnosis of pulmonary tuberculosis and other infectious diseases with respiratory organ involvement]. AB - The authors studied the information efficiency of stable-phased immunofermental analysis (IFA) in differential diagnosis of infectious diseases of respiratory system and pulmonary tuberculosis. IFA method was used on 60 infectious patients with non-tuberculous pathology, 64 patients with pulmonary tuberculosis and 200 donors. It was found out that the minimal diagnostical IFA titer in pulmonary tuberculosis was 1:320 (antibody revealing frequency--up to 89.2%; specificity- 95%). IFA method with phosphatide antigen has a great practical significance in differential diagnosis of influenza, acute respiratory viral infections and pneumonias with pulmonary tuberculosis. PMID- 8356823 TI - [Laboratory diagnostic experience in pyloric helicobacteriosis]. PMID- 8356824 TI - [Hypobaric hypoxia as a method for correction and rehabilitation in aviation medicine]. PMID- 8356825 TI - [The dynamics of the electroencephalogram indices in pilots with acute hypoxia]. AB - In experimental conditions the authors have modelled the state of acute hypoxia in pilots with disorders of high psychic functions. In the result of these researches it was found out that the changes of peak frequency of alpha rhythm anticipated the slow delta and theta rhythms. This EEG characteristic feature could be used for the development of a device which would control these states in pilots. PMID- 8356826 TI - [The professional fitness of the pilot]. PMID- 8356827 TI - [Typical pathology during the free immersion of a man under water]. AB - The free immersion of a man under the water is accompanied by the threat of specific disorders which could cause the drowning. The article examines the causes, conditions and mechanisms of two most frequent pathological states, i.e. the compression of thorax and loss consciousness caused by CO2 action and hypoxia. The symptoms of these states, as well as prophylactic measures and first aid recommendations are enclosed. PMID- 8356828 TI - [A comparative evaluation of tents for the deployment of small medical units]. PMID- 8356829 TI - [The medical evacuation work of Local Evacuation Point No. 44 of the Urals Military District during World War II]. PMID- 8356830 TI - [The use of personal computers in a military medicine department]. PMID- 8356832 TI - [A rapid assaying method for biotin determination and the computer program for data calculation]. AB - A rapid auxanographic method for biotin determination was established by means of a biotin auxotrophic yeast strain, and a computer program was designed to calculate the data obtained. Its determination concentration ranges from 0.3 to 5.0 micrograms/ml. The time-tested routine work in our laboratory proved that it is rapid, precis and reliable. PMID- 8356831 TI - [Purification and properties of beta-mannanases from alkalophilic Bacillus N16 5]. AB - Three extracellular alkaline beta-mannanases from an alkalophilic Bacillus N16-5 were purified to electrophoretic homogeneity by (NH4)2SO4 precipitation, DEAE Sephadex A-25 chromatography, hydroxyapatite chromatography and preparative electrophoresis. Molecular weights and pI values of the beta-mannanases (M-1, M-2 and M-3) were 51000, 38000 and 34700 by SDS-PAGE and 4.3, 2.5 and 2.5 by PAGEIEF, respectively. The optimum pH for enzyme catalysis were 9.0 for M-1 and 10.0 for M 2 and M-3, respectively. All of three enzymes were the most active at 70 degrees C. The activities of three enzymes were strongly inhibited by Ag1+, Hg2+ and Mn2+. Michaelis constants (Km) of the enzyme M-1, M-2 and M-3 for mannase from konjak were 2.9, 1.7 and 12.5 mg/ml, maximum velocities (Vmax) for the saccharide were 27500, 47500 and 15700 mumol.min-1.mg-1, respectively. Konjak was hydrolyzed by the enzyme M-1, and major components in digests were mono-, di-, tri- and tetra-saccharides. PMID- 8356833 TI - Reliability/validity issues. PMID- 8356834 TI - Evaluation of breast self-examination beliefs using a decision model. PMID- 8356835 TI - Parental perceptions of ethical issues post-NICU discharge. PMID- 8356836 TI - Making behavior changes after a myocardial infarction. PMID- 8356837 TI - Perceived control in patients with chronic obstructive pulmonary disease. PMID- 8356838 TI - Psychometric properties of a cognitive functioning scale for patients with traumatic brain injury. PMID- 8356839 TI - Obtaining and evaluating data sets for secondary analysis in nursing research. AB - Secondary analysis of existing data offers many advantages to the nurse researcher. Data from large-scale studies may be reanalyzed and refined by secondary analysts with a fresh perspective, thus enhancing the original study's contribution to scientific knowledge. High-quality data can be obtained for comparatively little expenditure of time and money. The secondary analyst, however, must exercise care in evaluating and analyzing a data set to maximize the internal and external validity of the reanalysis. Because the secondary analyst's lack of involvement in data collection procedures may decrease insight into the original study's limitations, vigilant skepticism should accompany all phases of the research process in secondary data analysis, just as it should in all other research. Miller (1982) advised, "Begin by assuming the worst and seek out the same kinds of information about sample selection procedures, sample size, response rates, field procedures, and coding conventions that you would insist on if you were collecting your own data" (p. 722). By systematically evaluating potential data sets according to rigorous predetermined criteria, the nurse researcher can minimize the possible pitfalls inherent in secondary analysis. On the other hand, investigators who use secondary sources appropriately can make significant contributions to nursing science at less cost than that engendered by traditional research methods. PMID- 8356840 TI - The reporting of consent rates in nursing dissertations. PMID- 8356841 TI - Nurses' reasons for participating in a longitudinal panel survey. PMID- 8356842 TI - Of postulates and peccadilloes: Robert Koch and vaccine (tuberculin) therapy for tuberculosis. AB - In August 1890, Robert Koch dramatically announced that he had discovered a cure for tuberculosis, and the world rejoiced. The miracle substance was subsequently revealed to be tuberculin, inoculated as a 'vaccine therapy'. However, within a matter of months his claims were disputed and debunked, and his reputation was grievously damaged. The nationalistic pressures, professional jealousies and pecuniary interests that drove Koch's premature announcement are reviewed here and discussed in a context relevant to the development of therapeutic vaccines for human immunodeficiency virus infections. PMID- 8356843 TI - Role of central nervous system and behaviour in the immune response. AB - Recent advances in antigen preparation and delivery have led to a renewed interest in vaccination to control infectious disease. However, relatively less attention has been devoted to host factors which affect the outcome of immune responses. There is now increasing acceptance that the central nervous and immune systems interact, and that this can be a bidirectional process. A range of behavioural and psychological states, learned responses and reactions to external stimuli have all been implicated in immune modulation. These interactions may occur via the direct innervation of lymphoid compartments, by paracrine means through the release of mediators from nerves situated in close proximity to cells involved in immunity, or by neuroendocrine signals in the form of hypothalamic, pituitary and peripheral endocrine hormones. These effects may account to some extent for unexplained variability in response to vaccination and disease challenge, through inherited or acquired differences in neuroendocrine or neurotransmitter responses to stress, circadian effects or learned behavioural responses. This review addresses the effects of environmental stimuli and behavioural manipulations on immune outcome and the response to vaccination, and the potential for practical application of these techniques in human and animal disease control and health management. PMID- 8356844 TI - AroD deletion attenuates Shigella flexneri strain 2457T and makes it a safe and efficacious oral vaccine in monkeys. AB - The aromatic-dependent live Shigella flexneri 2a vaccine strain SFL1070, with a deleted aroD gene, had a much reduced intracellular growth in HeLa cells compared with its parent strain S. flexneri 2457T. S. flexneri SFL1070 gave no adverse effects in eight Macaca fascicularis monkeys orally vaccinated with four doses of 1 x 10(11) live bacteria within a 5-week period, whereas S. flexneri 2457T caused dysentery in all eight non-vaccinated monkeys. Thus the aromatic dependency rendered S. flexneri SFL1070 significantly attenuated (p = 0.00008). Significant intestinal S. flexneri lipopolysaccharide (LPS)-specific sIgA responses were seen in seven of eight vaccinated monkeys (p < 0.01) after four doses with SFL1070. However, serum IgG or IgA responses to various S. flexneri LPS antigens and the invasion plasmid antigens (Ipa-s) were seen in only four of eight vaccinated monkeys. The serum IgG titre increases against S. flexneri Y and 2a LPS reached significant levels (p < or = 0.05). All but one of the vaccinated monkeys were protected against oral challenge with 1 x 10(10) or 1 x 10(11) live S. flexneri 2457T given 2 weeks after the last vaccination. The protection was highly significant (p = 0.0007) as all non-vaccinated monkeys challenged with equal doses of strain 2457T developed dysentery. Three of them succumbed. Challenge infection of vaccinated monkeys elicited serum IgA and IgG responses to the homologous S. flexneri 2a LPS in three monkeys each (0.005 < or = p < or = 0.025). Serum IgA and IgG responses to the Ipa-s were seen in five and four monkeys each (0.01 < p < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356845 TI - Prevention of transmission of simian immunodeficiency virus from vaccinated macaques that developed transient virus infection following challenge. AB - Macaque immunization with a mixture of four SIV peptides from conserved hydrophilic envelope regions has been shown to prevent virus persistence following challenge with SIVmne/E11s. Data shown here demonstrate that lymph node cells from all vaccinated monkeys and peripheral blood lymphocytes from one of the vaccinees were positive in a SIV-pol 'nested' polymerase chain reaction (PCR) amplification analysis. However, by 37 months after infection, all immunized monkeys were healthy while two of three controls had died and the remaining animal was virus culture-positive and had declining CD4+ lymphocytes. Viable lymph node cells and peripheral lymphoid cells in blood were transferred from the three immunized macaques to individual susceptible macaques. As a control for the transfer, one of the vaccine experiment controls that was actively producing virus in its peripheral blood was used. None of the recipients of cells from the vaccinated macaques seroconverted and all were virus coculture- and PCR-negative 25 weeks post-transfer (p.t.). The recipient of cells from the control infected macaque became positive in these tests by 2-3 weeks p.t. These results suggest that, while peptide-vaccinated macaques permitted some level of SIV replication following challenge, the vaccine prevented disease progression and virus transmission. PMID- 8356847 TI - Protection of mice against respiratory Bordetella pertussis infection by intranasal immunization with P.69 and FHA. AB - Intranasal immunization of adult female Balb/c mice with the Bordetella pertussis antigens FHA or P.69, greatly enhanced their ability to clear B. pertussis from their lungs following aerosol challenge compared with ovalbumin-immunized controls. Low numbers of lymphocytes secreting antibodies (IgG, IgA and IgM) against the immunizing antigens could be isolated from the lungs of immunized mice. Following aerosol challenge with B. pertussis there was a large increase in the numbers of FHA or P.69-specific antibody-secreting cells in the lungs of mice immunized with these antigens. Intranasal immunization, particularly with FHA, also primed mice to develop a systemic serum anti-pertussis antibody response subsequent to challenge. However, pulmonary clearance of B. pertussis correlated most closely with the local antibody response. A strong anti-FHA response was demonstrated in the lungs of mice that received a booster dose of FHA 9 months after their previous exposure to FHA, demonstrating that long immunological memory can develop in the murine respiratory tract following direct application of pertussis antigens to the respiratory tract mucosa. PMID- 8356848 TI - Global immunization against AIDS: economic considerations. AB - Many knowledgeable people believe that the only real hope for halting the AIDS pandemic rests with safe and effective HIV vaccines that are delivered through a global immunization programme. When such vaccines become a reality, the size of potential target populations for HIV vaccines may well be over 100 million. The costs associated with such a large vaccination programme probably reach the multi billion dollar level. An international consideration of financing strategies should begin in the near future in order to avoid a repetition of the lag between vaccine availability and widespread use that accompanied the introduction of hepatitis B vaccine. PMID- 8356846 TI - Immunization of institutionalized asthmatic children and patients with psychomotor retardation using live attenuated cold-adapted reassortment influenza A H1N1, H3N2 and B vaccines. AB - Live attenuated cold-adapted reassortant (CR) influenza virus vaccines were evaluated in institutionalized asthmatic children and severe psychomotor-retarded (SPR) patients. Almost all the vaccinees were seropositive to the vaccine strains before immunization. Trivalent CR vaccine (containing A H1N1 (CR-125), A H3N2 (CR 149) and B (CRB-117)), bivalent CR vaccine (CR-125 and CR-149) and monovalent CRB 117 were inoculated to 19 asthmatic children and 36 and 16 SPR patients, respectively. Overall 49, 22, and 11% of vaccinees were infected by A H1N1, A H3N2 or B vaccine viruses, respectively, as indicated by significant haemagglutination-inhibition (HI) antibody titre rises 4 weeks after inoculation. No severe adverse reactions associated with CR vaccination were observed in the handicapped patients. A nosocomial outbreak of influenza A H1N1 occurred in the ward with asthmatic children, but none of the 19 CR-trivalent vaccinees became infected. However, five of 20 non-vaccinees in the same ward, and ten of 30 vaccinees in another ward that received inactivated split vaccine became infected. The CR vaccines demonstrated significant protective effects against natural exposure to the A H1N1 virus, and were well tolerated and safe when given to patients with bronchial asthma and severe psychomotor retardation. PMID- 8356849 TI - [Cestode adaptation to life cycles]. AB - There are two groups of cestode adaptations. One of them makes it possible for particular developmental stages to be adapted to their particular environment (including second order environment). The second one involves passing through the entire life circle: transition from one environment to another, releasing from protective shells, host intrusion, population density regulation at different developmental stages. Spectrum of adaptive reactions on the life cycles is determined by peculiarities of parasite systems. PMID- 8356851 TI - The effect of storage on ice and various freezing treatments on enzyme leakage in muscle tissue of rainbow trout (Oncorhynchus mykiss). AB - In order to study the biochemical changes in fish muscle during ice storage and freezing-thawing processes, the activities of certain marker enzymes in the cell interstitial fluid from muscle tissue of rainbow trout (Oncorhynchus mykiss) were measured. The enzymes analysed were: lysosomal alpha-glucosidase (E.C. 3.2.1.20), beta-N-glucosaminidase (E.C. 3.2.1.30) and acid phosphatase (E.C. 3.1.3.2). The activity in centrifuged tissue fluid (CTF) was compared with the activity in total homogenate. When ice storage was varied between 3 and 14 days, it did not affect enzyme leakage into the CTF significantly. However, there was a distinct difference between fresh fish and fish iced even for only 1 day, which gave increased leakage of marker enzymes. When the ice-stored samples were subject to a freezing-thawing cycle they showed a marked increase in enzyme activity in the press juice. When the freezing process was varied so as to achieve different freezing rates, the slowest freezing rate caused the highest enzyme leakage. PMID- 8356850 TI - Bitter taste of enzymic hydrolysates of casein. I. Isolation, structural and sensorial analysis of peptides from tryptic hydrolysates of beta-casein. AB - beta-Casein A2 was isolated from milk of a homozygous cow and hydrolysed with trypsin. The hydrolysate was separated by RP-HPLC into 18 peptides, all but one of which could be attributed to the sequence of beta-casein on the basis of the amino acid composition. Some peptides overlapped. In total, they represented about 97% of the protein sequence. Only three peptides had a bitter taste, namely I49-N68 (recognition threshold 1.0 mg/ml, 0.45 mmol/l), I49-K97 (1.5 mg/ml, 0.28 mmol/l) and G203-V209 (0.175 mg/ml, 0.23 mmol/l). The contribution of the three peptides to the overall bitterness of the beta-casein hydrolysate (2.67 mg/ml) was about 11, 21, and 60%, respectively. Peptide I49-K97 was present in the hydrolysate together with its fragments I49-N68 and S69-K97. Remarkably, the smaller and more hydrophobic fragment I49-N68 was less bitter than I49-K97 on a molar basis, whereas the larger and more hydrophilic fragment S69-K97 had a neutral taste. These results show that in the case of larger peptides neither hydrophobicity nor size are responsible alone for bitter potency, but that conformational parameters must be of great importance. Furthermore, it can be concluded that only a part of the structure is responsible for the contact with the receptor. The bitterness of G203-V209 is discussed in connection with related synthetic peptides in the literature. PMID- 8356852 TI - [The effects of polylysine on the aggregation of surface and on the cleavage furrow of Rana amurensis eggs]. AB - Polylysine synchronously aggregated pigment granules and egg surface stained uniformly with fluorescein isothiocyanate to form patches (Plate I, fig 1 & 2). Patches always appeared and aggregated first in the opposite grey crescent region, then in grey crescent region and next at animal hemisphere. A fluorescent ring formed at the upper side of the equatorial region. The ring and the patches at the animal hemisphere accumulated to the animal pole to make a cap (Plate I, Fig. 3). Finally the vegetal hemisphere broke due to the contraction of egg surface during aggregation. These indicated that four different domains: opposite grey crescent region, grey crescent region, animal and vegetal hemispheres, were present at the fertilized egg surface. Similar domains also occurred at the unfertilized egg surface as revealed by the same treatment suggesting that the opposite grey crescent region of fertilized egg, which corresponding to the sperm entrance region had existed at the mature egg surface. There were three modes in the early stage of patch formation: (1) the features of granular protrusions did not change greatly (Plate I, Fig. 5-7), (2) the granular protrusions elongated (Plate I, Fig 8-11) and (3) folds radiated from patch (Plate I, Fig. 12, 13). Around each patch new surface membrane arose, which was similar to the nascent membrane of cleavage furrow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8356854 TI - [The characteristics of monoclonal antibodies and their antigens associated with human sperm acrosome reaction. II. Effects of the monoclonal antibodies on sperm function, sperm antigen localization and immunoblotting]. AB - By using microassay, the strong human sperm agglutination were caused by 9 of 23 monoclonal antibodies (McAbs) obtained by immunization with fresh human acrosome reacted (AR) sperm, which was induced by ionophore A 23187, but no one of them demonstrated the ability to immobilize human sperm. In contrast to most studies reported by other laboratories, the antigens recognized by most of McAbs in the present study were located in equatorial segment and midpiece of human sperm, and no one in acrosome region of human sperm. The binding pattern of some McAbs on non-treated and AR sperm was found to be different. The human sperm proteins ranged in the size of 16-146 kDa were demonstrated to be reacted with 9 of 23 McAbs by immunoblotting. Moreover, the cross reaction of 23 McAbs with mouse and tree shrew sperm was detected by indirect immunofluorescent assay. These results suggest that AR sperm possesses peculiar immunogenic properties. PMID- 8356853 TI - [The characteristics of monoclonal antibodies and their antigens associated with human sperm acrosome reaction. I. The induction of acrosome reaction and monoclonal antibody production]. AB - Sperm released from the male genital tract must undergo capacitation and acrosome reaction (AR) before binding to oocyte membrane. Changes of sperm components have been found after the capacitation and AR. Based on these changes, the new contraceptive methods and the treatment of the male infertility might be approached. In the present study, in vitro capacitated human sperm were induced to undergo AR in BWW-BSA medium with calcium ionophore A 23187. The fresh human AR sperm in about 50% of sperm population assayed by triple stain technique and/or chlortetracycline fluorescence staining were used for immunization. Twenty three murine hybridomas secreting monoclonal antibodies (McAbs) to non-treated (NT) and/or AR human sperm have been obtained. Of them, 21 McAbs were classified as IgM, others as IgG1 and IgG2a. Based on the immunoreactions of 23 McAbs with NT and AR sperm, they were divided into three groups: group A reacted mainly with the AR sperm, group B with NT sperm, and group C with both AR and NT sperm. The cross reaction of these McAbs with human leukemia cell lines was detected by ELISA and the discrepant reactions were observed. PMID- 8356855 TI - [Plant regeneration from hypocotyl protoplasts of Lycium barbarum L]. AB - The hypocotyl protoplasts of Lycium barbarum L. CV. Ningji No. 1 were isolated in an enzyme mixture solution containing 1% cellulase and 1% pectinase. The protoplasts were cultured in KM 8 p liquid medium containing 0.3 mg/L 2,4-D and 0.3 mg/L BA, The first division of regenerated cells occurred 3 days after culture. The small cell clumps could be observed by naked eyes 20 days after culture. 40 days after culture, microcalli of 1-2 mm in size were transferred to MS solid differentiation medium containing 3% sugar, 0.1-0.4 mg/L BA and 0.05-0.1 mg/L NAA. About 30 days after culture on MS solid medium, the calli with shoots were transferred to 1/2 MS medium containing 0.1 mg/L BA and 0.2 mg/L IBA, from which 80% of them differentiated roots and regenerated whole plantlets. PMID- 8356856 TI - Comparison of the ventilatory effects of morphine and buprenorphine in children. AB - This study was a prospective, randomized comparison of the ventilatory effects of equianalgesic single-doses of morphine, 100 micrograms/kg, and buprenorphine, 3.0 micrograms/kg, administered intravenously to 20 children (5-8 years of age) after elective ophthalmic surgery. The decrease in ventilatory rate and acute change in the arteriolar oxygen saturation and the increase in end-tidal CO2 levels were statistically significantly greater in magnitude and duration after buprenorphine than after morphine. For both drugs, the time, duration and magnitude of ventilatory changes varied appreciably between individuals. No child had apnea or hypoventilation requiring assistance. The authors conclude that acutely administered buprenorphine depresses ventilation to a greater degree than morphine. The maximal ventilatory effect of buprenorphine occurs later than with morphine, and ventilatory depression after buprenorphine may develop late. For safety, all children given opioids intravenously should be observed until they are fully responsive and ventilatory control has stabilized. PMID- 8356857 TI - Glycopyrrolate vs. atropine during anaesthesia for laryngoscopy and bronchoscopy. AB - As glycopyrrolate has been reported superior to atropine with respect to reduction of salivation, stability of cardiac rate and rhythm, and recovery, a comparison of these properties of the two drugs and placebo was made in 45 patients undergoing direct laryngoscopy and 45 patients undergoing bronchoscopy, in most cases followed by mediastinoscopy. When given i.m. 30 min before anesthesia (midazolam, alfentanil, thiopentone, and suxamethonium), the two test drugs were found to be equally potent regarding the antisialogogic effect. The same increase in heart rate after the test drugs was seen before induction, and during anaesthesia heart rate rose to the same level in the placebo group as the test groups. During anaesthesia, blood pressure was lowest in the atropine group. No differences could be demonstrated with respect to cardiac arrhythmias, possibly due to the small size of the material. The present study gives no reason for preferring either drug, and only the efficacy of both test drugs in controlling airway secretions provides an argument for using any anticholinergic drug when laryngoscopy or bronchoscopy is performed under the conditions of the present study. PMID- 8356858 TI - Effective concentration 50 for propofol with and without 67% nitrous oxide. AB - The Effective Blood Concentration (EC) of propofol required to prevent response to surgical incision was determined in 65 ASA I or II female patients breathing either 100% oxygen or 67% N2O in oxygen. Propofol was administered via a microcomputer-controlled infusion system programmed to maintain the blood propofol concentration at predetermined target values. The blood propofol concentrations predicted by the micro-computer were validated by measurement of whole blood propofol concentration. Predicted and measured concentrations differed during infusion of propofol, but became similar after discontinuing the infusion for at least 90 s, suggesting that equilibration within the central compartment was incomplete during infusion. The response to the initial incision was observed and probit analysis used to determine the predicted blood concentration at which 50% of patients responded. The predicted EC50 for propofol/N2O/O2 and propofol/O2 was 4.5 micrograms ml-1 and 6.0 micrograms ml-1 respectively, and the measured EC50 propofol/N2O/O2 and propofol/O2 was 5.36 micrograms ml-1 and 8.1 micrograms ml-1, 67% nitrous oxide in oxygen reducing the predicted EC50 by 25% and the measured EC50 of propofol by 33%. The predicted EC may be more representative of the equilibrated concentration in the central compartment and thus reflective of tissue propofol concentrations. PMID- 8356859 TI - Favorable effects of epidural analgesia on hemodynamics, oxygenation and metabolic variables in the immediate post-anesthetic period. AB - Fourteen adult patients undergoing elective major abdominal surgery were divided into two groups. One group received epidural and general anesthesia (epidural group), and 20 ml of 0.125% bupivacaine and 2 mg of morphine were administered epidurally about 30 min before the end of the operation for post-anesthetic analgesia. The other group (control group) received general anesthesia alone with nitrous oxide, oxygen and enflurane. Flow-directed pulmonary arterial and radial arterial catheters were inserted preoperatively, and hemodynamic, respiratory, neuroendocrine and metabolic variables were measured serially. The data were compared during anesthesia and the immediate post-anesthetic recovery period. In the control group, the plasma epinephrine level in the post-anesthetic recovery period increased about four times over the anesthetic period. Oxygen consumption was increased and mixed venous oxygen saturation was decreased significantly. There was a close linear correlation between oxygen consumption (Y) and plasma epinephrine (X) level: Y = 285.7X + 90.5 (P < 0.01, r = 0.72). On the other hand, plasma epinephrine, oxygen consumption and mixed venous oxygen saturation did not change significantly in the epidural group in the post-anesthetic recovery period. There was also a close linear correlation between oxygen consumption (Y) and oxygen delivery (X): Y = 0.22X-32.0 (P < 0.01, r = 0.89). We conclude that the surgical stress and anesthetic reversal may seriously influence neuroendocrine responses and subsequently increase plasma epinephrine. Tissue oxygenation and metabolic imbalance may occur due to the rapid increase of epinephrine in the post-anesthetic recovery period. Epidural analgesia at this period may play a more important role and have a more favorable effect on the tissue metabolism. PMID- 8356860 TI - Complications and late sequelae following nasotracheal intubation. AB - A total of 379 patients admitted to the ICU for mechanical ventilation were prospectively investigated for lesions on the nose, nasal cavity, ears and larynx during and after nasotracheal intubation. One to two years later, the surviving patients were questioned to investigate late persisting sequelae. During intubation and up to 5 days following extubation, inflammatory changes and ulceration of the nostrils or nasal septum were found in 76 (20%) and 110 patients (29%), respectively. There were bleedings from the nasal cavity in 67 (19%) and fractures of the conchae in 40 patients (11%). Hoarseness was noted in 135 patients (42%). Inflammatory changes and ulcerations of the nostril and nasal septum were correlated to the duration of intubation. Among the 281 patients included in the follow-up study, 100 (35%) had symptoms from the nose and nasal cavity. Sixty-five (24%) had symptoms related to the ears, 56 (20%) to the maxillary sinus, 81 (29%) to the voice and 90 (32%) to the throat. Increasing duration of intubation was found to be correlated to persisting symptoms from the larynx. Former ulcerations of the nose were associated with a tendency to nasal bleeding. To avoid as many complications as possible from the nose and nasal cavity, we recommend orotracheal intubation. As late sequelae from the larynx increase with the duration of intubation, perhaps tracheostomy should be performed earlier than is general practice today, but that has to be proven in forthcoming studies. PMID- 8356861 TI - Effect of single-dose omeprazole and ranitidine on gastric juice acidity and volume in patients undergoing laparotomy. AB - The effects of oral omeprazole and oral ranitidine on gastric fluid volume and pH were compared in 95 elective surgical patients, randomly assigned to one of three groups. The patients received either 80 mg of omeprazole or 300 mg of ranitidine orally at 6.00 on the morning of surgery. One third of the patients received no antacid therapy. Following induction, a no. 18 nasogastric tube was passed into the stomach and all available gastric fluid was aspirated. pH and volumes were measured. In the omeprazole- and ranitidine-treated groups, the mean pH was > 5.4 after induction, at completion of surgery and 1 h after operation, although at least one patient in both groups had pH < 2.5. The volumes of gastric aspirates were reduced equally by both drugs. Two patients in the omeprazole group, none in the ranitidine group and eight in the control group (26%) had pH < 2.5 with volume > 25 ml at induction. Both drugs appeared to be effective in reducing the volume of intragastric fluid and acidity to acceptable values. PMID- 8356862 TI - Fluidity state of lymphocyte plasma membrane in malignant hyperthermia susceptible pigs and humans. AB - Recent studies suggest that abnormalities occur at the lipid level in malignant hyperthermia susceptible humans and pigs. To test this hypothesis, we first investigated the physical state of plasma membranes of lymphocytes isolated from normal and malignant hyperthermia susceptible swine. In halothane-challenged pigs, malignant hyperthermia susceptibility was also assessed by ryanodine binding assay on purified sarcoplasmic reticulum membranes. The results clearly show that plasma membrane of lymphocytes from malignant hyperthermic pigs are significantly more fluid than controls. We then attempted to apply the same methodology to lymphocytes prepared from human patients previously diagnosed by the halothane and caffeine contracture test. In that case, there was no clear relationship between malignant hyperthermia susceptibility and the fluidity state of lymphocyte plasma membranes. PMID- 8356863 TI - The influence of different procedures of general anaesthesia on platelet function, coagulation and the fibrinolytic system. AB - We investigated whether different procedures during general anaesthesia alter platelet activation in vivo and/or activate coagulation and fibrinolysis. Forty one healthy adult patients, scheduled for elective ophthalmic surgery under general anaesthesia, were studied with regard to changes of plasma beta thromboglobulin (beta TG, index of platelet activation), thrombin-antithrombin III-complex (TAT, index of activation of coagulation) and d-dimer (index of fibrinolysis) during anaesthesia. The patients underwent either inhalation anaesthesia with enflurane and nitrous oxide or balanced anaesthesia with enflurane (0.5% end-tidal concentration) and alfentanil. Ten minutes after intubation the beta TG level was significantly reduced compared to the preoperative value in both general anaesthesia groups. Balanced anaesthesia caused a moderate but significant increase of TAT values at 10 min after extubation. No significant change in d-dimer levels was seen. Presuming a minimal effect of the surgical procedure on the determined variables, we conclude that none of the anaesthetic procedures induces platelet activation and fibrinolysis. The clinical relevance of the moderate coagulation activation during balanced anaesthesia remains to be investigated. PMID- 8356864 TI - Effects of propofol on mean arterial pressure and systemic vascular resistance during cardiopulmonary bypass. AB - This study was designed to evaluate the effects of propofol on mean arterial pressure (MAP) and systemic vascular resistance (SVR) during cardiopulmonary bypass (CPB). Twenty patients were divided randomly for administration of 2 mg.kg 1 propofol (group Propofol, n = 10) or 0.9% saline solution (group Control, n = 10) during CPB. The two groups were comparable with respect to sex, age, height, type of surgery (valvular or coronary), arterial hypertension and preoperative antihypertensive treatment. Only their weight and body surface area were significantly different (control group vs propofol group, respectively: 78.5 +/- 14.4 vs 64.7 +/- 7.7 kg, P < 0.05; and 1.85 +/- 0.2 vs 1.68 +/- 0.13 m2, P < 0.05). MAP, SVR and SVR index were significantly lower in the propofol group than in the control group at 10, 15 and 20 min of study, suggesting that the hypotensive effect of a bolus injection of propofol is due, at least in part, to a direct decrease in the SVR. PMID- 8356865 TI - CSF neuropeptides in cancer pain: effects of spinal opioid therapy. AB - The cerebrospinal fluid (CSF) levels of the opioid peptides met-enkephalin (ME), beta-endorphin (BE) and dynorphin (DYN) as well as the putative sensory neuropeptides substance P (SP), somatostatin (SOM), calcitonin gene related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were determined in 10 patients with severe nociceptive pain due to malignancy, before and after initiation of spinal opioid therapy, and in 10 control patients. Pain intensity, evaluated by means of a 100-mm visual analog scale (VAS), was reduced from 39 +/- 9 to 18 +/- 10 for continuous pain and from 70 +/- 10 to 10 +/- 8 for intermittent pain (means +/- s.e.mean). Lumbar CSF immunoreactive ME and DYN concentrations were significantly increased (P = 0.05) and BE and VIP were significantly decreased (P < or = 0.05) in the pain patients. A slight, but non significant (P = 0.06) decrease in SP-like immunoreactivity was found after initiation of spinal opioid therapy. Visceral pain seemed to be associated with low immunoreactive SP and ME concentrations compared to somatic pain. A highly significant correlation was found between SP and ME (P < 0.001) and to a lesser extent also between other peptides. We conclude that the concentrations of the endogenous opioids were more affected by nociceptive pain states than the non opioid peptides. The origin of pain may also influence the results. The postulated inhibition of peptide release by spinal opioid application seemed to be present for SP, but could otherwise not be confirmed. PMID- 8356866 TI - Low-flow isoflurane-nitrous oxide anaesthesia offers substantial economic advantages over high- and medium-flow isoflurane-nitrous oxide anaesthesia. AB - Isoflurane consumption was studied for three different fresh gas flows in patients scheduled for major elective abdominal, urological or gynaecological surgery under general anaesthesia with an expected duration of 2 h or more. Thirty patients were randomly assigned to either high-flow anaesthesia using a partial rebreathing system without carbon dioxide absorption (Mapleson D) or medium- or low-flow anaesthesia using a circle system with carbon dioxide absorption. Patients were anaesthetised with isoflurane in 40% oxygen and 60% nitrous oxide. The amount of isoflurane consumed was measured with a precision scale. The total consumption of liquid isoflurane (mean +/- s.d.) during the first 2 h was 40.8 +/- 12.2 ml in the high-flow group, 18.5 +/- 5.4 ml in the medium-flow group and 7.9 +/- 2.2 ml in the low-flow group. The corresponding cost of isoflurane for the three groups was 214 Danish kroner (DKK) (19.5 pounds), 97 DKK (8.8 pounds) and 42 DKK (3.8 pounds), respectively. The calculated total cost of anaesthetics was 286 DKK (26 pounds), 155 DKK (14.1 pounds) and 91 DKK (8.3 pounds), respectively. In conclusion, low-flow isoflurane nitrous oxide anaesthesia offers substantial economic advantages over high- and medium-flow isoflurane-nitrous oxide anaesthesia. PMID- 8356867 TI - Epidural anesthesia in a patient with myasthenia gravis. AB - We present a patient with myasthenia gravis who was safely managed by epidural anesthesia during and after thymectomy. An epidural catheter was inserted via the C7-T1 intervertebral space and 2% lidocaine was used during the surgery. The level of analgesia as determined by pinprick extending from C5 to T6. Epidural morphine or morphine and bupivacaine were used for postoperative pain relief. We evaluated ventilatory responses to CO2 and hypoxia after epidural anesthesia with lidocaine or morphine, and during continuous epidural infusion of the mixture of morphine and bupivacaine. Ventilatory responses to CO2 and hypoxia were both depressed following epidural injection of morphine. However, depression of ventilatory responses was not demonstrated following continuous epidural infusion of a mixture of morphine and bupivacaine. This case report suggests that epidural anesthesia is useful as a primary anesthetic and for postoperative pain control in patients with myasthenia gravis. PMID- 8356868 TI - Inhibition of brain cell excitability by lidocaine, QX314, and tetrodotoxin: a mechanism for analgesia from infused local anesthetics? AB - Local anesthetic infusions have been used to provide analgesia in a variety of painful conditions. The mechanism for this drug effect remains unknown. To better define the electrical effects of lidocaine concentrations comparable to those obtained during analgesic infusions, lidocaine (0.05-3 mmol.l-1), QX314 (an obligatorily charged, quaternary lidocaine derivative applied within the cells), and tetrodotoxin (10 mmol.l-1) were applied to rat hippocampal pyramidal cells. The three drugs, which inhibit Na+ currents by varying mechanisms, produced tonic increases in (firing) current threshold, and decreases in the amplitude of action potentials measured using an intracellular microelectrode technique. Lidocaine inhibited action potential spikes and increased current threshold in a concentration-dependent fashion. Lidocaine 50 and 100 mumol.l-1 did not inhibit action potentials, but increased firing threshold by nearly 100%. Lidocaine 1-3 mmol.l-1 significantly inhibited action potential amplitude and increased threshold by as much as 800%. Similarly, QX314 and tetrodotoxin produced greater increases in current threshold than in action potential amplitude. QX314 produced phasic (or frequency-dependent) block during trains of stimuli at 1 Hz, even when almost no tonic block was present. Lidocaine produced less phasic block than QX314, and required both greater tonic block and more frequent stimulation to produce the phenomenon. Tetrodotoxin demonstrated no phasic block. Increases in current threshold occurred in lidocaine concentrations associated with analgesia and toxicity; inhibition of action potentials occurred scarcely at all at these concentrations. Thus, tonic increases in current threshold may underlie analgesia and supplementation of general anesthesia by intravenous lidocaine. PMID- 8356869 TI - Significance of centro-temporal spikes on the EEG. AB - In a prospectively studied group of 43 children with centro-temporal spikes on the EEG, only 26 had the classical epileptic syndrome related to this EEG abnormality. Ten patients never had epileptic manifestations. In the other seven cases two types of epileptiform activity were encountered: in addition to the centro-temporal spikes generalized spike-and-wave complexes or--in other patients -occipital epileptiform phenomena occurred. In these cases the clinical signs and symptoms correlated best with the non-Rolandic EEG abnormalities. Some patients had only a few centro-temporal spikes during the recording of the EEG; in others this epileptiform activity was almost continuously present. This quantitative difference had no clinical correlation. Centro-temporal spikes should probably be looked upon as an (epi)phenomenon of cerebral disfunction with a wide range of clinical and electroencephalographic expressions. PMID- 8356870 TI - Outcome of resective surgery for intractable partial epilepsy guided by subdural electrode arrays. AB - The aim of this paper was to evaluate the outcome and the factors predictive for a good prognosis of resective surgery for intractable partial epilepsy guided by subdural electrode arrays (SEA's) and operative electrocorticography. Sixty-four patients, aged 8-52 years, were evaluated with chronic SEAs in order to record interictal and ictal activity and delineate speech and motor areas by functionally mapping. Resection were individualized to each patient's SEA recorded electrocorticogram and operative electrocorticogram and functional mapping results (tailored resection). The follow-up time was a minimum of one year. Good seizure outcome was defined as seizure free from complex partial and secondary generalized seizures. After one year 70% of the patients with a temporal ictal focus was seizure free compared to 55% of the patients with an extra-temporal focus. Complete resection of interictal or ictal fields as mapped with SEAs, gave better prognosis than partial resection. Patients with no postresection spikes had a better prognosis than patients with residual postresection spikes evaluated with operative electrocorticography. Sex, age, duration of epilepsy prior to surgery, extent of temporal lobe resection and structural abnormalities determined by MRI were not associated with a favorable seizure outcome after surgery. We conclude that complete resection of the interictal and ictal field mapped with SEA's and absence of postresection spikes on operative electrocorticography are associated with an excellent seizure outcome. PMID- 8356871 TI - Epilepsy treatment in The Netherlands. Comparison of two medical centres. AB - In order to test if it is feasible to compare epilepsy treatment policies, a secondary (University Hospital) and a tertiary referral care centre (i.e. an Epilepsy Centre) were compared with respect to their characteristics, the treatment approaches, and the outcome of treatment using clinimetric indexes. At the Epilepsy Centre a greater variety of seizure types was seen than at the University Hospital. At the University Hospital more patients were treated with monotherapy (62.5%) than at the Epilepsy Centre (28.0%). The Composite Index of Impairments (CII), which reflects all treatment related impairments i.e. seizures and adverse events, was significantly higher at the Epilepsy Centre than at the University Hospital. No difference was seen in the groups of patients with a high score of the CII (> 100). Further analysis is needed to obtain an answer as to why differences between the two groups exist. PMID- 8356872 TI - Amyotrophic lateral sclerosis in Sardinia, Italy: an epidemiologic study. AB - The authors carried out an epidemiologic study on amyotrophic lateral sclerosis in Sardinia for the years 1957 through 1990. The duration of the disease and survival were significantly shorter in bulbar form. The distribution of ALS in various areas of the island was found to be not at all homogeneous. Mean yearly incidence showed no significant variations in the decades 1971-80 and 1981-90. In the last decade, an increase of bulbar forms was observed. PMID- 8356873 TI - Absence of brain antibodies in the sera of relapsing-remitting multiple sclerosis patients is not due to the formation of immune complexes. AB - Using an enzyme-linked immunoadsorbent assay, we looked, whether the formation of idiotype-anti-idiotype complexes was responsible for the absence of antibodies in the sera of MS patients. We tested 18 relapsing-remitting and 26 chronic progressive patients versus 44 age- and sex-matched controls. We did not find elevated titres of immune complexes in the sera of the multiple sclerosis patients. PMID- 8356874 TI - Effects of recombinant alpha-2b-interferon therapy in patients with progressive MS. AB - The effects of systemic recombinant interferon-alpha-2b were studied in 6 carefully selected patients with progressive multiple sclerosis. 3.0 million IU were given as daily subcutaneous injections for 6 months, 5 patients showed worsening disability, and in 4 of them new or enlarged lesions were detected in MRI. In one patient no change in disability was found; his MRI showed regressed changes. The mean progression index during the treatment was significantly higher (p < 0.02) than during the previous 2 to 3 years' period of continuous progression. The frequency of peripheral blood natural killer (CD16+) cells declined significantly 3 months during the treatment, but returned to the pretreatment values after termination the treatment. An increase of intrathecal IgG synthesis and oligoclonal bands was demonstrated in 4 and 3 patients, respectively. Our experience suggests that long-term recombinant IFN-alpha-2b treatment may activate the immunological process of MS. PMID- 8356875 TI - Mercury and multiple sclerosis. AB - It has occasionally been claimed that multiple sclerosis (MS) may be due to a chronic mercury intoxication, e.g. from mercury liberated from dental fillings. Therefore, the present communication compares the mercury content assayed by neutron activation in 8 macroscopically normal areas (frontal lobe) of MS autopsy brains with those of 8 control samples. No significant differences could be traced between the two groups concerning total mercury. However, the lipid soluble mercury (preferably methyl mercury) expressed per cell unit (DNA) was found significantly decreased in MS. These data may be explained either by a wash out of lipid soluble mercury due to break-down of the blood-brain barrier in MS or to abnormalities in methylation processes probably related to the vitamin B12 metabolism in MS. PMID- 8356876 TI - Serial study of neuropsychological performance and gadolinium-enhanced MRI in MS. AB - Many multiple sclerosis patients show cognitive decline, although no definite correlation between brain demyelination at MRI and neuropsychological performance has been found so far. We submitted a group of nine relapsing-remitting, mildly disabled patients to both serial gadolinium-DTPA enhanced MRI and neuropsychological evaluation in a follow up period of three months. Despite the great variability in acute lesions' load, no overall decline in test, performance was found. Furthermore, in selected cases whose test scores declined at follow up, no concordance with the new lesion load was found. PMID- 8356877 TI - Clinical characteristics of familial and sporadic Creutzfeldt-Jakob disease in Finland. AB - The clinical features of 44 Finnish patients with Creutzfeldt-Jakob disease (CJD) were analyzed with special emphasis on the differences between the sporadic and familial forms. The 32 sporadic patients comprised all neuropathologically verified cases of CJD in 1974-89 in Finland. The 12 familial patients were members of the same pedigree where CJD has been linked with a mutation at codon 178 of the PRNP gene. The median age at the onset of the disease was 62.5 years and median duration 4.5 months in sporadic patients, and 49 years and 20.5 months in familial CJD, respectively. 90 percent of both sporadic and familial patients had myoclonus. Typical periodic EEG change was seen in 72% of sporadic patients, whereas the familial patients showed only a progressive slowing of EEG. PMID- 8356878 TI - Serum cobalamin and methylmalonic acid in Alzheimer dementia. AB - The cobalamin status was evaluated in Alzheimer dementia (n = 26), other dementias (n = 24), various gerontopsychiatric disorders (n = 25), and in neuro psychiatrically healthy controls (n = 20). Supplementing serum cobalamin we measured methylmalonic acid (MMA), a metabolite accumulating early in cobalamin deficiency. Subnormal cobalamin and/or clearly elevated MMA concentrations were found in 11 cases: 7 Alzheimer patients (27%), 2 with other dementias (8%), one psychiatric patient (4%), and one control (5%). None presented the typical neurologic features of cobalamin deficiency and macrocytosis was found in only one. The mean cobalamin concentration was significantly lower in Alzheimer patients (179 +/- 18 pmol/l) than in the age-matched controls (256 +/- 23 pmol/l) (p = 0.013) and the other patient groups. Correspondingly, the mean MMA level was higher in the Alzheimer group (0.480 +/- 0.062 mumol/l) than in any other diagnostic group (controls: 0.347 +/- 0.040 mumol/l). Comparing the Alzheimer group to the other groups as a whole, the elevation was significant (p = 0.0097). Our findings indicate that Alzheimer patients are particularly prone to cobalamin deficiency, and even subtle biochemical signs of deficiency seem to justify treatment. PMID- 8356879 TI - Chronobiological aspects of acute cerebrovascular diseases. AB - The study was aimed at further investigating the circadian and circannual patterns of stroke onset. Study design and type of participants: 977 strokes (475 in men and 502 in women) concerning 926 subjects (457 men and 469 women) admitted to Ferrara Hospital in two calendar years (1990-1991), were prospectively investigated. The strokes were classified as based on cerebral infarction (CI), transient ischemic attack (TIA) and cerebral hemorrhage (CH: subarachnoid and intracerebral hemorrhage). Two statistical models of analysis were used. The assessment of circadian and circannual periodicity was performed utilizing the single cosinor method. A separate analysis was performed after distribution of events into 6-hour intervals, and chi-square test for fit was applied to the number of observed versus expected cases. The majority of strokes occurred in the morning between 7 a.m. and noon (35% of cases) and the hypothesis of a uniform distribution of the time onset was rejected on the basis of the chi-square for all subtypes of stroke. A circadian rhythm was found for CI and TIA with acrophase at the 11.56 and 12.41 respectively. Also a circannual periodicity was found for CI with a prevalent peak in October. The spectral analysis detected a circadian cycle for CH having a period of 4 h, and a circannual cycle for TIA with a period of 4 months. This study confirms that stroke is a high-chrono-risk disease, with specific circadian and circannual rhythms. This is very important for a better understanding and control of the underlying factors and in terms of prevention. PMID- 8356880 TI - Transcranial Doppler recordings in raised intracranial pressure. AB - The pulsatility index (PI) registered by the transcranial doppler (TCD) was examined in relation to arterial pCO2 (paCO2) and epidural pressure (ICP). In 10 normal subjects PI was studied during variations in paCO2. In 10 neurosurgical patients with head injuries concomitant measurements of PI and ICP were obtained. The results showed a negative exponential correlation between PI and paCO2. PI changes with 3.2% pr mmHg paCO2. A positive exponential correlation between PI and ICP was observed. PI changed with 2.4% pr mmHg ICP. In the subgroup of patients with raised ICP (15 mmHg <) paCO2 was found not to influence the PI reflection of the ICP, probably because paCO2-changes affected PI as well as ICP. The results suggest that the noninvasive bedside TCD-registration may be a useful marker of the ICP and probably replace the former invasive methods of measuring ICP. PMID- 8356881 TI - Overlapping syndrome of MERRF and MELAS: molecular and neuroradiological studies. AB - We describe a 42-year-old woman with overlapping syndrome of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonus epilepsy and ragged-red fibers). Clinically, she had episodic headache, stroke-like episode with left hemiparesis and lactic acidosis commonly found in MELAS syndrome. However, myoclonus seizure, and ataxia with dyssynergic gait characteristic of MERRF were also noted. Computed tomographic scans showed a right temporo-parietal hypodense lesion. The lesion disappeared 20 months later, even magnetic resonance images also failed to reveal this abnormality. A molecular analysis of mitochondrial DNA was conducted by using restriction endonucleases ApaI and NaeI. A transition from A to G was found at the nucleotide position 3243, but not found at the 8344th nucleotide pair. In this report, we document the fluctuating CT changes and emphasize the importance of molecular analysis in patients with overlapping syndrome of mitochondrial encephalomyopathies. PMID- 8356882 TI - Diagnosis of X-adrenoleucodystrophy phenotypic variants. AB - We report the radiological and biochemical data of a familial X adrenoleucodystrophy with an extreme phenotypic variability, in which the diagnosis of several affected members was delayed for several years. The propositus developed a progressive dementia, while two of his brothers were diagnosed of primary Addison's disease several years previously. MRI in two cases with different phenotypes revealed hyperintense diffuse white matter lesions, and the diagnosis was confirmed by increased serum levels of very long chain fatty acids. We conclude that X-adrenoleucodystrophy should be included in the differential diagnosis of adult Addison's disease even though no neurological involvement or family history is recorded, and that MRI is a useful tool for diagnosis and follow-up of neurological involvement in this disease. PMID- 8356883 TI - Idiopathic intracranial hypertension after ofloxacin treatment. AB - We report the occurrence of idiopathic intracranial hypertension in a patient treated with ofloxacin, a fluoroquinolone antimicrobial agent, for 16 months. The withdrawal of ofloxacin and acetazolamide therapy were followed by a complete recovery of visual function. PMID- 8356884 TI - Post-traumatic segmental myoclonus associated with bilateral olivary hypertrophy. AB - We present clinical and magnetic resonance (MR) findings in three patients with segmental myoclonia occurring 11-18 months after severe brainstem injury. Palatal myoclonus and vertical ocular myorhythmia were present in all three patients and synchronous involuntary movements of the upper extremities ("wing beating") in two patients. MR-imaging showed multiple post-traumatic lesions within the dentato-rubro-olivary pathway ("myoclonic triangle"), associated with bilateral enlargement and increased signal intensity of the inferior olives. The signal abnormality was more prominent on proton density weighted images than on T2 weighted images, suggesting underlying pathological changes different from typical gliosis. PMID- 8356885 TI - Impairment of Fos protein formation in the rat infarct borderzone by MK-801, but not by NBQX. AB - In the present immunocytochemical study, we investigated the mechanism of Fos protein induction and the regional distribution of the Fos protein in brains of spontaneously hypertensive rats subjected to 2 h of permanent middle cerebral artery occlusion (MCAO). Rats were administered either saline or a glutamate receptor antagonist; the non-competitive NMDA receptor antagonist MK-801 or the AMPA receptor antagonist NBQX which are known to be able to reduce infarct size in MCA occluded rats. The saline treated rats showed presence of Fos protein in nerve cell nuclei throughout the cortical and striatal infarct borderzone, but no staining in the infarct core or contralateral hemisphere. MK-801 almost totally abolished this expression of Fos protein whereas NBQX had no significant effect on Fos protein expression. It is suggested that the Fos protein induction is due to repeated spreading depressions mediated by NMDA receptors in the infarct borderzone, and that Fos protein due to its persistence in the tissue can be used as a histochemical marker of borderzone tissue at risk for eventually becoming recruited in the infarct. PMID- 8356887 TI - Satisfaction with care reported by psychiatric inpatients. Relationship to diagnosis and medical treatment. AB - In this survey, 274 patients were sent a questionnaire concerning satisfaction with psychiatric treatment and the ward 1 month after their discharge from hospital. Fifty-two percent of the patients responded. Answers to the 56 items of patient satisfaction were analyzed in relation to patient diagnoses and treatment given. Patients who were diagnosed as suffering from affective disorders or from reactive psychoses were more satisfied than patients with schizophrenia or paranoia or with transitory adjustment reactions. Patients who had no personality disorder diagnosis and patients with character neurosis were more satisfied than patients with antisocial or borderline personality disorders. Patients on antidepressant medication were much more satisfied than other patients. The results of the study are discussed with regard to the need of further research in this area and to quality assurance. PMID- 8356886 TI - Cross-cultural comparison of depression and depressive symptoms in older people. AB - This article presents data on the prevalence of depression and the profile of depressive symptoms in 2 groups of people aged 65 and over: 1070 living in Liverpool, United Kingdom, and 1080 living in Zaragoza, Spain. Similar prevalence figures were found for women (Liverpool first); 14.2% vs 14.8% and, for men, 7.2% vs 6.2%. No age differences were found. The figures are lower than those found using similar methods in London and New York, but higher than those from Iceland. The article also compares the profile of depressive symptoms between Liverpool and Zaragoza and explains these by reference to social and cultural differences. PMID- 8356888 TI - The anterior pituitary responds normally to protirelin in obsessive-compulsive disorder: evidence to support a neuroendocrine serotonergic deficit. AB - The prolactin and thyroid-stimulating hormone (TSH) responses to protirelin and the prolactin and cortisol responses to d-fenfluramine were measured in 8 outpatients with DSM-III-R obsessive-compulsive disorder (OCD). The results were compared to those in 8 age- and sex-matched healthy controls. The responses to d fenfluramine were significantly attenuated in the OCD patients, but there was no significant difference between the responses to protirelin in OCD patients and healthy controls. The data suggest that, in OCD, blunting of prolactin responses to the serotonin-releasing agent d-fenfluramine is due to a central abnormality and not due to a pituitary deficit. PMID- 8356889 TI - Impulsivity and dyscontrol in bulimia nervosa: is impulsivity an independent phenomenon or a marker of severity? AB - Fifty-eight normal-weight DSM-III-R bulimia nervosa patients were compared with 27 normal controls on measures of bulimia nervosa, depression, impulsivity, obsessionality and impulse control (dyscontrol) behaviours. Patients scored higher than controls on all these measures. Almost half the patient cohort met Lacey's multi-impulsive bulimia criteria. When bulimic symptoms were controlled for in an analysis of covariance, multi-impulsive bulimics did not score significantly differently to non-impulsive bulimics on psychometric measures of impulsivity, obsessionality and depression. The concept of impulsivity is critically reviewed and newer concepts linking obsessionality and impulsivity are explored. PMID- 8356890 TI - Psychotic features and the course of Alzheimer's disease: relationship to cognitive, electroencephalographic and computerized tomography findings. AB - Thirty-one of 50 patients satisfying the NINCDS-ADRDA criteria of probable or possible Alzheimer's disease showed psychotic features during a 2-year observation period. Paranoid delusions were reported in 23 patients, delusional misidentification in 17, visual hallucinations in 16 and auditory hallucinations in 8. All of the 7 patients who died within the observation period had suffered from psychotic features even before the preterminal phase of illness. A faster progression of illness towards more severe stages of dementia was associated with paranoid delusions and hallucinations but not with delusional misidentification. We could not prove a significant influence of age, age of onset, cognitive performance, ventricular enlargement or the severity of quantitative electroencephalographic changes at initial examination on the course of illness. This may indicate that specific psychotic features and their potential organic substrate exert an effect on the progression of illness and on survival in Alzheimer's disease, which is not related to gross brain atrophy and generalized neurophysiological changes. PMID- 8356891 TI - Reproductive rates in schizophrenic outpatients. AB - We investigated the marriage rates, the reproductive rates and the marital reproductivity of schizophrenic outpatients in Japan. A total of 553 patients with DSM-III-R-diagnosed schizophrenia at the Teikyo University Hospital, Tokyo, Japan were compared with age- and sex-matched outpatients at surgical clinics of the same hospital. Our findings indicate that the reproductivity of schizophrenics is reduced, even though the sample consists of outpatient population and modern operational diagnostic criteria have been used. The marriage rate and reproductive rate of the schizophrenics were reduced, especially in men. The number of married men was significantly less than that of married women and the reduced marital reproductivity was found in women but not men. These findings indicate that the reduced reproductivity of men in accounted for largely by a reduced rate of marriage, and that in women is accounted for partly by lower rate of reproductivity within marriage. PMID- 8356892 TI - Clinical significance of outcome in long-term follow-up of borderline patients at a day hospital. AB - All borderline patients admitted at a day hospital during a 6-year period were followed up with a postal questionnaire after 3-10 years. Patients who had chosen to leave the treatment within 4 months were analyzed as a separate group, and these drop-outs and the remaining patients were compared with a group of well adjusted people who were assumed to represent the functional norm. The patients who remained in treatment were clearly posited at a level of functioning between the norm and the drop-outs, although the variation among them was quite large. Depending on the stringency and content of the criterion of clinical significance, 25-75% of the patients remaining in treatment fell within the range of the norm group versus 20-50% of the drop-outs. The patients who had benefited most since termination had differed favorably from the other patients already at admission to treatment, but not as much as had the drop-outs. The drop-outs, however, at admission also had more ambivalent or negative attitudes towards treatment. PMID- 8356894 TI - Brief family therapy with alcohol-dependent men in Trinidad and Tobago. AB - This study--the first of its kind in the English-speaking Caribbean--investigated the efficacy of modified brief family therapy in the treatment of alcoholism. Thirty men were treated with family therapy and milieu therapy and compared with 30 sex- and age-matched patients treated with milieu therapy alone. Follow-up over a period of 1 year showed significant levels of improvement in those treated with family therapy. The treatment group did not revert to their original drinking pattern. This can be attributed to family therapy. Family therapy was brief and involved seeing all significant members for 3 sessions, each session lasting 90 min. The role of family therapy and importance of culture in management of these patients are discussed. Our study confirms that a time limited problem-solving family therapy approach is of use in these ethnic groups. PMID- 8356893 TI - The pattern of regional cerebral blood flow during alcohol withdrawal--a single photon emission tomography study with 99mTc-HMPAO. AB - Cerebral blood flow was investigated during alcohol withdrawal in 15 male alcoholics by single photon emission computerized tomography with 99mTc-HMPAO and compared with the results of a second study 3 weeks later when all symptoms of withdrawal had disappeared and when the patients had been free of medication for at least 1 week. Slice images were reconstructed parallel to the orbitomeatal plane, and tracer activity was analyzed in 8 regions of interest per hemisphere. During alcohol withdrawal a special pattern of cerebral blood flow distribution could be observed. Relative perfusion was elevated in both inferior temporal regions, whereas it was reduced in the superior temporal region of both hemispheres. The changes of cerebral blood flow distribution did not correlate with neuropsychological findings nor with the severity of withdrawal syndrome. PMID- 8356895 TI - The Utrecht comparative study on psychiatric day treatment and inpatient treatment. AB - A prospective randomized comparative study on the effectiveness of psychiatric day treatment and inpatient treatment is described. The target population consisted of patients who would normally have been admitted to an open inpatient unit. Outcome indicators were psychopathology, social functioning, interpersonal functioning, social network and social support. No differences in effectiveness were found between the two forms of treatment, although more patients accepted and completed day treatment, and day patients were more satisfied. Although a uniform treatment programme for both departments was established, distinct differences did arise in the actual treatment programme offered to the patients. The duration of treatment for the day patients was considerably longer, and the intensity of treatment was more low-key. No striking differences in the amount of medication prescribed and in the occurrence of crisis situations (including suicide) were found. Day treatment turns out to be a realistic alternative for 33% of all patients admitted for inpatient treatment. It was not possible to predict which type of patient in particular is suitable for day treatment. PMID- 8356896 TI - Outcome, recovery, relapse and mortality across six years in patients with clinical eating disorders. AB - The study describes course and outcome over 6 years for adults with eating disorders. Special interest is paid to clinically critical events such as relapse and premature death. Seventy-seven per cent of the 30 prospectively studied patients had no eating disorder diagnosis after 6 years. Among the recovered patients, the total risk of relapse was 48%. The mortality was 17.8 times higher than expected. The overall pattern of results confirm earlier ones for anorexia nervosa and extend the limited database for bulimia nervosa. Of particular importance may be 1) that no patient in this sample suffered more than one major relapse and 2) that the risk for premature death may be twice as high among bulimic as among restricting patients. PMID- 8356897 TI - Effect of a long-lasting gonadotrophin hormone-releasing hormone agonist in six cases of severe male paraphilia. AB - Six men with severe paraphilia had been treated with depot gonadotrophin luteinizing releasing hormone analogue (GnRHa) (triptorelin 3.75 mg per month intramuscularly). In 5 cases, the treatment ended their deviant sexual behavior and markedly decreased their sexual fantasies and activities without further significant side effects than those related to hypoandrogenism. This clinical improvement was parallel to the gradual decrease of plasma testosterone level to castration values within the first month. The beneficial effect of this treatment had been maintained at follow-up varying from 7 months to 3 years. One patient interrupted the treatment at the end of the first year and relapsed within 10 weeks. GnRHa treatment, which leads to reversible castration, may constitute a promising treatment of paraphilic behavior and may favor the possibility of concurrent psychotherapy. PMID- 8356899 TI - Development of personality disorders in children and adolescents with obsessive compulsive disorder. A 6- to 22-year follow-up study. AB - Forty-seven people with admissions in childhood for obsessive-compulsive disorder (OCD) and 49 child psychiatric controls were followed up in young adulthood and assessed for DSM-III-R personality disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders. The number of personality disorders in OCD patients did not differ significantly from the number in controls. The most common personality disorder was avoidant personality disorder (significantly more frequent than in controls), whereas obsessive-compulsive personality disorder (OCPD) was not found more often in the OCD group. Subjects with OCD in adulthood seemed to have OCPD more often than childhood OCD patients with no OCD at follow-up. In the whole group, histrionic personality disorders were more common in women than in men and OCPD more common in men than in women, whereas borderline personality disorder was most common among women in the OCD group. The presence of a personality disorder in adulthood could not be correlated with such childhood factors as social background, symptoms or age of onset of OCD. PMID- 8356898 TI - Suicide and attempted suicide reported by general practitioners in Belgium, 1990 1991. AB - In 1990-1991 the Belgian sentinel network of general practitioners recorded suicide and suicide attempts within their practices. The annual attempted suicide rate is estimated at 13.0 cases per 10,000 inhabitants. The highest incidence rates are found among women and young people. The annual suicide rate is estimated at 2.3 cases per 10,000 inhabitants, with the highest rates in men and in elderly people. The highest incidence rates of suicide attempts as well as of suicide are found among divorced people. About 30% of the attempters and committers made at least one earlier attempt. Drug overdose and hanging are the most frequently used methods, respectively when attempting and committing suicide. About 60% of both committers and attempters contacted their general practitioner within a period of 1 month preceding the attempt. Nearly half of the attempters and of the committers were treated for a mental disorder in the year preceding the attempt. PMID- 8356900 TI - Peripheral nerve regeneration: role of growth factors and their receptors. AB - Growth factors play a central role in the regulation of normal and injury-induced regenerative cell growth. The purpose of this article is to summarize the available data on the expression of different growth factors and their receptors in the injured peripheral nervous system and to discuss their possible role in promoting peripheral nerve regeneration. PMID- 8356901 TI - Developmental profile of glucocorticoid binding to synaptic plasma membrane from rat brain. AB - The plasma membranes of several mammalian tissues including the brain are known to have specific binding sites for glucocorticoids. The developmental changes in specific glucocorticoid binding to synaptic plasma membrane (SPM) from rat brain were determined at various postnatal ages, using [3H]triamcinolone acetonide (TA) as the steroid ligand. The specific binding of the labeled glucocorticoid to SPM during the first 2 postnatal weeks was only 40% of the adult level. An increase of the specific binding occurred after day 15, and this developmental rise of binding reached the adult level approximately by the end of the fourth week. Methodologically, these developmental data are detailed in the present article to include nonspecific binding as well as specific binding. Scatchard analysis indicates that the developmental rise of the specific glucocorticoid binding was due to an increase in the membrane binding sites. The ontogenetic increase of membrane binding sites during postnatal brain development provides additional evidence that these binding sites have physiological significance in brain function. PMID- 8356902 TI - Trophic influences of human and rat amniotic fluid on neural tube-derived rat fetal cells. AB - Normal human (week 17-20) and rat (E16-17) amniotic fluids were used as culture media for primary cultures of rat fetal (E 16) cortical, mesencephalic and striatal cell dissociates, or astroglial subcultures from the same brain regions. Phase-bright and dark cells were identified under phase contrast microscopy and their cell processes were measured utilizing semi-automated procedures. Subcultured astroglia were immuno-reacted against glial fibrillary acidic protein and fibronectin. Rat and human amniotic fluid allowed survival and growth of neuronal and non-neuronal cells. Human amniotic fluid samples were trophic in variable degrees. Cerebral cortex subcultured astroglia usually expressed a radial-like morphotype. Although charcoal-adsorbed human amniotic fluid was trophic for primary cultures, its ability to sustain neuritic growth depended on its degree of trophism before treatment. Growth of cell processes in neuronal- and glial-like cells in primary cultures was inhibited to different degrees by the addition of antisera towards nerve or epidermal growth factors. It is concluded that amniotic fluid constitutes a trophic medium for astroglia and neurons. Both, nerve and epidermal growth factors appear to be necessary for growth of cell processes in neuronal and glial primary cultures in amniotic fluid. Trophic effect of amniotic fluid on subcultured astroglia did not seem to be diminished by nerve growth factor antiserum. The role of amniotic fluid during the early phases of brain organogenesis is discussed. PMID- 8356903 TI - Laminar expression of m1-, m3- and m4-muscarinic cholinergic receptor genes in the developing rat visual cortex using in situ hybridization histochemistry. Effect of monocular visual deprivation. AB - The postnatal development of laminar pattern of m1-, m3- and m4-mRNA-muscarinic acetylcholine receptor subtypes in the visual cortex of both normally raised and monocularly deprived rats (one eyelid sutured at the age of 11 days) was studied using in situ hybridization histochemistry and computer-assisted image analysis. From birth until day 15 the level of m1-receptor transcript in layer II/III increases markedly as compared to deeper layers. From day 15 up to day 18 a transient bimodal pattern develops with peaks in layers II/III and VI. Already on day 35 a more homogeneous distribution of m1-receptor mRNA level is detectable persisting until adulthood. In contrast, the m3-receptor mRNA shows already at birth a bimodal distribution with peaks in layers II/III and VI. Further development until adulthood results in transient changes in the ratio of the mRNA levels in these layers. In the adult visual cortex a similar laminar pattern as at birth is observed. From day 1 up to day 10 a relative increase in the mRNA level of the m4-receptor in layers II to IV is observed. From day 10 until day 15 a bimodal distribution of receptor mRNA develops with peaks in layers III and VI which is similar to the adult stage. However, between days 18 and 35 a shift in the laminar receptor mRNA distribution occurs resulting in peaks in layers IV and VI. The labeling of the m5-receptor transcript in rat visual cortex was very weak and did not show any alteration with age. Unilateral eyelid closure from postnatal day 11 resulted in transient changes in the laminar distribution of m3- and m4-receptor mRNA between postnatal days 18 and 25, whereas the development of the laminar pattern of the m1-receptor mRNA was not affected regardless of the length of visual deprivation. The distinct laminar developmental pattern of mRNA muscarinic receptor subtypes in rat visual cortex suggests specific roles of the muscarinic receptor subtypes during the first weeks of postnatal maturation of visual function. PMID- 8356904 TI - Hippocampal cholinergic alterations and related behavioral deficits after early exposure to ethanol. AB - The present study was designed to ascertain septohippocampal cholinergic alterations and their related behavioral deficits after early exposure to ethanol. Mouse pups were exposed to ethanol, 3 g/kg by daily subcutaneous injection on postnatal days 2-14. At age 50 days, the ethanol-exposed mice had significant reductions from control levels in eight-arm maze performance. For example, on the fourth testing day, the number of correct entries in the ethanol group was 21% below control levels (P < 0.05) and the number of trials needed to enter all arms was 48% above control (P < 0.001). It took the ethanol-exposed mice twice the time to reach criterion than it did control (P < 0.01). A 33% increase from control level in muscarinic receptor number (Bmax) was found in the treated mice of age 22 days and a 64% increase at age 50 days (P < 0.001). However, no differences between control and treated groups could be detected in the presynaptic component of the cholinergic innervation, choline acetyltransferase activity. The results suggest that early ethanol exposure acts on hippocampal function similarly to phenobarbital, probably via alterations in postsynaptic processes in the septohippocampal cholinergic pathways. PMID- 8356905 TI - Structural aspects of N-hydroxy-N'-aminoguanidine derivatives as inhibitors of L1210 cell growth and ribonucleotide reductase activity. AB - Previous studies have shown that N-hydroxy-N'-aminoguanidine (HAG) derivatives [RCH = NNHC(= NH)NHOH-tosylate] inhibit ribonucleotide reductase activity and block the growth of leukemia L1210 cells and human colon carcinoma, HT-29, cells in culture. In the current studies, the role of the side chains and the location of the bond of the side chain moiety to HAG were investigated using a new series of HAG derivatives which contained as the R-group--cyclohexyl, phenyl-, pyridyl- or napthyl moieties. The effects of these compounds as inhibitors of L1210 cell growth and ribonucleotide reductase activity were compared with the parent compound. N-hydroxy-N'-aminoguanidine was less inhibitory to ribonucleotide reductase activity and L1210 cell growth than hydroxyurea. The phenyl-HAG compounds which included 1-benzyloxybenzylidene- and 4 cyclohexylmethoxybenzylidene-HAG inhibited CDP reductase with IC50s which ranged from 50-110 microM. 1-Naphthylmethylene-HAG was more inhibitory than 2 naphthylmethylene-HAG and more inhibitory than the phenyl-HAG compounds. 2 Pyridylmethylene-HAG was more inhibitory than 3-pyridylmethylene- or 4 pyridylmethylene-HAG. While HAG inhibited CDP and ADP reductase activities essentially to the same extent, the HAG-derivatives inhibited ADP reductase activity to a greater extent than CDP reductase activity. Cyclohexylmethylene-HAG did not inhibit either L1210 cell growth or ribonucleotide reductase activity. There was good correlation between the inhibition of ribonucleotide reductase activity and L1210 cell growth by these HAG-derivatives. These data indicate that not only is the nature of the side chain substitution important, but also the location of the HAG-moiety on the ring position. PMID- 8356906 TI - Regulation of proteasome expression in developing and transformed cells. AB - The proteasome is a unique protease complex found in all eukaryotic cells and has multiple functions for essential activities. In this work we showed that it is expressed at high level in immature, rapidly growing cells, such as those in early embryonic tissues and cancer cells (Fig. 7). The increase of its expression is down-regulated on differentiation of the cells. However, lymphatic blastocytes grow rapidly and express high levels of proteasomes, but are differentiated. Therefore, the proteasome is not expressed at high levels only in immature cells, but is also involved specifically in nuclear activities of cells during rapid growth, possibly regulating proteinous factors in the cell cycle. PMID- 8356907 TI - Peroxisomal leukotriene degradation: biochemical and clinical implications. AB - Degradation of the cysteinyl leukotrienes LTE4 and N-acetyl-LTE4, and of LTB4 by beta-oxidation from the omega-end has been recognized as an important pathway in the inactivation of these mediators. The contribution of peroxisomes to leukotriene degradation and inactivation was studied in isolated hepatocytes, in isolated liver peroxisomes, and in patients with inherited peroxisome deficiency. (1) Isolated hepatocytes from rats pretreated with the peroxisome proliferator clofibrate produced highly increased amounts of beta-oxidation products derived from omega-carboxy-LTB4 and omega-carboxy-N-acetyl-LTE4 as compared to normal hepatocytes. (2) Isolated peroxisomes purified from normal and clofibrate-treated liver produced omega-carboxy-dinor-LTB4 and omega-carboxy-tetranor-LTB3 when nucleotide cofactors, including CoA, ATP, NAD+, FAD, and NADPH, were added. beta Oxidation of the cysteinyl leukotriene omega-carboxy-N-acetyl-LTE4 was observed only with isolated peroxisomes together with a microsome fraction providing an acyl-CoA synthetase activity. (3) Peroxisomal leukotriene-binding proteins were identified by photo-affinity labeling with omega-carboxy-[3H]leukotrienes and precipitation of labeled polypeptides with antibodies against enzymes of the peroxisomal beta-oxidation system. (4) Peroxisomal degradation of leukotrienes in humans was studied by analyses of endogenous leukotrienes and their catabolites in urine from patients with an inherited peroxisomal deficiency disorder (Zellweger syndrome) and healthy infant controls. Urinary LTE4, relative to creatinine, was increased 10-fold in the patients, whereas the beta-oxidation product omega-carboxy-tetranor-LTE3 was only detectable in healthy infants. In addition, LTB4 was exclusively detected in the urine of patients with peroxisome deficiency. The increased levels of biologically active, proinflammatory mediators might be of pathophysiological significance. In addition, the altered pattern of leukotriene metabolites in urine may be of diagnostic value. The measurements in these patients underline the essential role of peroxisomes in the catabolism and inactivation of leukotrienes in humans. PMID- 8356908 TI - Role of glutathione in cellular resistance to alkylating agents. AB - Both elevated glutathione levels and increased activity of the enzyme glutathione S-transferase have been associated with the resistance of cells to alkylating agents. We have demonstrated that one mechanism of this resistance is the inactivation of the alkylating agents by conjugation with glutathione. This conjugation can be catalyzed by glutathione S-transferase. For the nitrogen mustard agents we have studied, both the spontaneous and enzyme catalyzed reactions proceed through the aziridinium intermediates of the alkylating agents, and the alpha isoenzymes of GST are involved. In a study of cyclophosphamide resistant medulloblastoma cell lines elevated cellular concentrations of glutathione correlated well with the resistance of the cell lines. PMID- 8356909 TI - Chemical modification of an arginine residue in aldose reductase is enhanced by coenzyme binding: further evidence for conformational change during the reaction mechanism. AB - Chemical modification of pig muscle aldose reductase (ALR2) with the arginine specific reagent phenylglyoxal resulted in the inactivation of the enzyme. This inactivation exhibited pseudo-first order kinetics typical of active-site directed chemical modification. Inactivation of ALR2 by [7-C14] phenylglyoxal in the absence of NADPH or NADP+ followed by tryptic digestion resulted in the isolation by HPLC of one major and one minor radioactive peptide. Protein sequencing revealed that the major peptide contained a modified arg268, a residue located in the coenzyme binding site. The minor radioactive peptide and the single radioactive peptide isolated from ALR2 inactivated in the presence of NADP+ contained chemically modified arg293. The arginine residue modified at the active site is positioned to bind the 2'-OH phosphate group of the ribose sugar of the adenine moiety of NADP+. Arg293 is present on the C-terminal loop of ALR2. The enhancement of Arg293 modification by phenylglyoxal in the presence of NADP+ indicates that this C-terminal loop may be involved in the slow conformational change that occurs during the reaction sequence upon coenzyme binding. PMID- 8356910 TI - Nucleoside transport in normal and neoplastic cells. AB - The permeation of nucleosides across the plasma membrane of mammalian cells is complex and mediated by at least five distinct transporters that differ in their sensitivity to inhibitors and in their specificity for nucleosides. The basic properties and permeant specificity of these transporters are summarized in Table 3. It appears that there may be differences in the distribution of these transporters in tumors and normal tissues that might be exploited for chemotherapeutic purposes. The human tumor cell lines examined express predominantly the NBMPR-sensitive equilibrative transporter es which can be blocked by low concentrations of NBMPR and dipyridamole. It is reasonable to expect that tumors with transport properties similar to the CCRF-CEM and Rh28 cell lines (Table 1) that have no detectable NBMPR-insensitive transport activity will be highly susceptible to the therapeutic approach of combining a transport inhibitor such as dipyridamole or NBMPR with an inhibitor of de novo pyrimidine biosynthesis. On the other hand, this approach to therapy is unlikely to succeed against tumors with transport phenotypes similar to the WI-L2 cell line that may permit the salvage nucleosides in the presence of these inhibitors. The majority of tumor cells examined, however, fall between these extremes, and it is not yet known what level of NBMPR-insensitive transport activity can be tolerated without seriously compromising this therapeutic approach. With respect to normal tissues, the mature absorptive cells of the intestine have predominantly Na(+)-dependent nucleoside transporters that are insensitive to NBMPR and dipyridamole. The proliferating crypt cells also appear to have Na(+)-dependent nucleoside transport, although they may also have an NBMPR-sensitive component of transport (Belt, unpublished data). Bone marrow granulocyte-macrophage progenitor cells also appear to have one or more concentrative nucleoside transporters. Thus these tissues, which are most vulnerable to the toxicity of antimetabolites, may be able to salvage nucleosides in the presence of inhibitors of equilibrative transport and be protected from the toxicity of de novo synthesis inhibitors. It is likely, however, that a successful application of this therapeutic approach will require the analysis of the nucleoside transport phenotype of individual tumors in order to identify those patients that may benefit from such therapy. Since the development of antibodies and cDNA probes for the various nucleoside transporters is currently underway in several laboratories, it is likely that analysis of the nucleoside transport phenotype of tumors from biopsy material will be feasible in the future. PMID- 8356911 TI - Molecular cloning of the branched-chain alpha-keto acid dehydrogenase kinase and the CoA-dependent methylmalonate semialdehyde dehydrogenase. AB - The complete amino acid sequence of rat liver CoA-dependent methylmalonate semialdehyde dehydrogenase, the enzyme responsible for the oxidative decarboxylation of malonate- and methylmalonate semialdehydes to acetyl- and propionyl-CoA in the distal portions of the valine and pyrimidine catabolic pathways, has been deduced from overlapping cDNAs obtained by screening a lambda gt11 library with nondegenerate oligonucleotide probes synthesized according to PCR-amplified portions coding for the N-terminal amino acid sequence of the enzyme. Although unique because of its requirement for coenzyme A, the methylmalonate semialdehyde dehydrogenase clearly belongs to the aldehyde dehydrogenase superfamily of enzymes. Quantitation of mRNA and protein levels indicates tissue-specific expression of methylmalonate semialdehyde dehydrogenase. A large increase in expression of methylmalonate semialdehyde dehydrogenase occurs during 3T3-L1 preadipocyte differentiation into adipocytes. The complete amino acid sequence of rat liver branched-chain alpha-ketoacid dehydrogenase kinase, the enzyme responsible for phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, was deduced from a cDNA cloned by a procedure similar to that described above for the methylmalonate semialdehyde dehydrogenase. Expression of the cDNA in E. coli yielded a protein that phosphorylated and inactivated the branched-chain alpha-ketoacid dehydrogenase complex. Very little sequence similarity between branched-chain alpha-ketoacid dehydrogenase kinase and other eukaryotic protein kinases could be identified. However, a high degree of similarity within subdomains characteristic of prokaryotic histidine protein kinases was apparent. Thus, this first mitochondrial protein kinase to be cloned appears closer, evolutionarily, to the prokaryotic histidine protein kinases than eukaryotic ser/thr protein kinases. PMID- 8356912 TI - Suppression of ras-mediated transformation. Differential expression of genes encoding extracellular matrix proteins in normal, transformed and revertant cells. AB - A subtraction hybridization technique was used to identify genes specifically expressed in phenotypic revertants derived from cells transformed by the H-ras oncogene. The expression of genes coding for components of the extracellular matrix appears to be frequently down-regulated in transformed cells. Partial restoration is associated with the reexpression of the normal phenotype in revertants. PMID- 8356913 TI - The electrophile counterattack response: protection against neoplasia and toxicity. AB - Exposure of rodents or their cells in culture to low doses of a wide variety of chemical agents, many of which are electrophiles, evokes a coordinated metabolic response that protects these systems against the toxicity (including mutagenicity and carcinogenicity) of higher doses of the same or other electrophiles. This response involves enhanced transcription of Phase 2 enzymes: glutathione transferases, NAD(P)H:quinone reductase, UDP-glucuronsyltransferases, and epoxide hydrolase, as well as the elevation of intracellular levels of reduced glutathione. We suggest that this cellular adaptation, which occurs in the liver and many peripheral tissues, be designated as the "Electrophile Counterattack" response. Seven families of highly diverse chemical agents that elicit this response include: oxidatively labile diphenols and quinones; Michael reaction acceptors (olefins conjugated to electron-withdrawing groups); isothiocyanates; organic hydroperoxides; vicinal dimercaptans; trivalent arsenicals; heavy metals (HgCl2, CdCl2) as well as mercury derivatives with high affinities for sulfhydryl groups; and 1,2-dithiole-3-thiones. An analysis of the molecular mechanisms of these enzyme inductions was carried out by transient expression in hepatoma cells of a plasmid containing a 41-bp enhancer element derived from the 5'-upstream region of the mouse glutathione transferase Ya gene, and the promoter region of this gene, linked to a human growth hormone reporter gene. The concentrations of 28 inducers (belonging to the seven chemical classes) required to double growth hormone production in this system spanned a range of four orders of magnitude and were closely and linearly correlated with the concentrations of the same compounds required to double the specific activity of quinone reductase in murine hepatoma cells. We therefore conclude that the regulation of these Phase 2 enzymes (and possibly also that of glutathione synthesis) by all of these inducers is mediated by the same enhancer element that contains AP-1-like sites. Similar enhancer sequences are present in the rat glutathione transferase Ya gene, and in the upstream regulatory regions of the quinone reductase genes of rat and human liver. PMID- 8356914 TI - Lithium increases accumulation of second messenger inositol 1,4,5-trisphosphate in brain cortex slices in species ranging from mouse to monkey. AB - Historical aspects of the phosphoinositide field are briefly reviewed. The effects of the anti-manic depressive drug, lithium, on inositol 1,4,5 trisphosphate accumulation in brain cortex slices in species ranging from mouse to monkey are presented. In the guinea pig, lithium, in the presence of acetylcholine, increases the accumulation of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate, but at therapeutic concentrations of lithium 1 mM inositol is required to see a statistically significant effect. In previous studies in rat brain cortex slices, lithium inhibited accumulation of inositol 1,4,5-trisphosphate by 15-20%. We have confirmed this and found a similar effect in mouse brain cortex slices. However, if we added 20-30 mM inositol we observed lithium-stimulated accumulations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in these two latter species. These observations in rat and mouse appear to relate to the following facts: (1) brain cortices of mouse and rat contain in vivo concentrations of inositol half that of guinea pig, (2) incubated rat brain cortex slices are depleted of inositol by 80% and (3) the slices require 10 mM inositol supplementation to restore in vivo concentrations. More recently, we have shown that in monkey brain cortex slices, therapeutic concentrations of Li+ increase accumulation of inositol 1,4,5-trisphosphate. Inositol 1,3,4,5-tetrakisphosphate is not increased. Neither inositol, nor an agonist, is required. The same effects are seen whether inositol 1,4,5 trisphosphate is measured by the [3H]inositol-prelabelling technique or by mass assay, although mass includes a pool of inositol 1,4,5-trisphosphate which is metabolically inactive. Thus, in a therapeutically relevant model for man, Li+ increases Ins(1,4,5)P3 in brain cortex slices, as was previously seen in lower mammals at nonrate-limiting concentrations of inositol. PMID- 8356915 TI - Studies on the mechanism of the cytotoxic action of the mitomycin antibiotics in hypoxic and oxygenated EMT6 cells. AB - The mitomycin antibiotics, because of their preferential toxicities for hypoxic cells, have significant potential as adjuncts to ionizing radiation in the treatment of solid tumors. To gain information on the mechanism by which these agents exert their cytotoxicities to hypoxic and aerobic cells, the effects of MC, POR and several of their analogs were studied in EMT6 mammary carcinoma cells. The rate of uptake of POR by these cells was directly correlated with the cytotoxicity produced by this agent under both hypoxia and aeration. At equivalent concentrations, uptake of POR into hypoxic cells was more rapid than into aerobic cells. Hypoxic cells also accumulated the antibiotic in concentrations well in excess of that present in the extracellular medium, presumably as a result of reductive activation and covalent binding of POR to cellular structures. Such activation and binding occur to a much lesser degree in aerated cells, resulting in the rapid efflux of POR from these cells when the antibiotic is removed from the extracellular environment. To gain information on the reaction of POR with DNA, mono- and bis-adducts formed in EMT6 cells exposed to this agent were measured. Three major adducts were formed. Two were mono adducts consisting of deoxyguanosine linked at its N2-position to the C-1 of POR and of 10-decarbamoyl POR. The third was a bis-adduct in which POR was cross linked to two deoxyguanosines at their N2-positions. More adducts were formed in hypoxia than in air, and more bis-adducts were present in hypoxic cells. Simultaneous exposure of cells to both POR and DIC reduced the total adduct level and a new unknown adduct was formed, primarily under hypoxia. Several mitomycins were evaluated for their capacity to kill EMT6 cells and to produce DNA cross links in both hypoxia and aeration. The number of cross-links required to produce a given amount of cell kill was similar, regardless of the mitomycin employed or the degree of oxygenation. The findings support the concept that DNA is a critical target in the action of the mitomycins and that cross-linking of the DNA creates an important lesion for cytodestruction. PMID- 8356916 TI - Regulation of deoxycytidine kinase activity and inhibition by DFDC. AB - (1) Deoxycytidine kinase activity increased in a transformation- and progression linked fashion in rat hepatomas of different proliferation rates. The activity also increased and was growth rate-linked in a series of tissue culture cell lines of human and animal tumors. (2) Deoxycytidine kinase activity was stringently linked with expression of the neoplastic proliferative program as it sharply increased in log phase in tissue culture cells of hepatoma 3924A and several human carcinoma strains. (3) Deoxycytidine kinase is subject to nutritional and hormonal regulation. On starvation the activity in liver decreased and on refeeding it returned to normal. Steroid hormone increased liver enzymic activity. Deoxycytidine kinase is substrate-inducible, since deoxycytidine injections in rat led to a 2- to 3-fold increase in hepatic enzyme activity. (4) Actinomycin or cycloheximide treatment blocked the increase in liver deoxycytidine kinase activity induced by steroid or deoxycytidine treatment. Therefore, it is assumed that the rise in deoxycytidine kinase activity requires new RNA and protein synthesis. (5) Cycloheximide treatment of rats carrying hepatomas yielded a t1/2 = 3.4 hr in the tumor for deoxycytidine kinase activity which was the shortest among the examined enzymes of purine and pyrimidine biosynthesis. (6) Actinomycin treatment of rats carrying hepatomas yielded a t1/2 of 5.8 hr for deoxycytidine kinase activity in the tumor which was one of the shortest in the examined enzymes of purine and pyrimidine biosynthesis. (7) Difluorodeoxycytidine (DFDC) is a competitive inhibitor (Ki = 7 28 microM) of deoxycytidine kinase from rat hepatoma and from human pancreatic carcinoma and ovarian carcinoma cells in culture. PMID- 8356917 TI - Regulation of human deoxycytidine kinase expression. AB - The human deoxycytidine kinase gene is a single copy gene and is comprised of seven exons that are spread over more than 34 kb of the genome. The 5'-flanking region is highly G/C rich and does not contain CAAT or TATA boxes. This region, when cloned into a recorder gene construct containing the chloramphenicol acetyltransferase gene, is capable of mediating CAT activity in human lymphoid cell lines and appears to have greater activity in human T, as compared to B, lymphoblast cell lines. The expression of the gene at the mRNA level does not appear to be cell-cycle regulated in that the levels of mRNA in human peripheral blood T lymphocytes remain constant as the cells progress from a resting to a proliferating state. Since this enzyme catalyzes the conversion of a number of chemotherapeutic agents to their corresponding monophosphate form and is thus essential for their activation, it will be important to define further the genetic elements which regulate the expression of this gene. PMID- 8356918 TI - Oxidation resistant muteins of antileukoproteinase as potential therapeutic agents. AB - Native antileukoproteinase (ALP) and two oxidant resistant mutants ALP 242 and ALP 231 were synthesized by means of recombinant DNA technology. In the ALP 242 molecule the methionine residue located in the reactive centre of the binding loop is replaced by a leucine residue. In ALP 231 all four methionine residues of the second domain were substituted by leucine residues. The native inhibitor and the two oxidant resistant molecules show comparable inhibitory capacities towards human neutrophil elastase (HLE) and cathepsin G. All three inhibitors were treated with different reactive oxygen species. After incubation with chloramine T or supernatants of activated polymorphonuclear leukocytes (PMN's) a drastic drop of inhibitory capacity of the native molecule was observed. Compared to the native form of ALP the mutant ALP 242 was less inactivated, whereas ALP 231 was nearly totally resistant towards all reactive oxygen. (Heinzel-Wieland R. et al., Biomed Biochim Acta 50: 677-681 (1991)) The intratracheal administration of HLE into the lung of Syrian Hamsters induced mild to moderate emphysematous lesions. The inhibitory potencies of native ALP and the ALP mutants were determined in this animal model by means of intratracheal instillation of the different molecules one hour prior to the administration of HLE. The inhibitory effects of ALP 242 and ALP 231 towards HLE-induced emphysema were significantly better than that of the native molecule. Surprisingly no significant differences between the two mutants were observed. (Rudolphus A. et al., Clin Sci 81: 777-784 (1991)) In a second animal model the emphysema was induced by repeated intratracheal administration of lipopolysaccharides (LPS) into the hamster lungs. This model is characterized by a chronic process of inflammation probably caused by a continuous release of endogenous elastase from infiltrating PMN's. Repeated applications of 1 mg of ALP 242 reduced the LPS-induced emphysema by 70 to 80%. In contrast, equal amounts of the native molecule resulted in significantly lower inhibition of the LPS-induced emphysema, only 23-30% reduction was observed. Repeated applications of 1 mg of ALP 231 reduced the LPS-induced emphysema only about 50%. So far it is not yet clear, why the totally oxidant resistant ALP 231 was less effective than the ALP 242 molecule. (Stolk J. et al., Pulmonary Pharmacology in press (1992)) PMID- 8356919 TI - Factor XII activation and inhibition in inflammation. AB - Biochemical observations during clinical sepsis using functional and immunological measurements of enzymes, cofactors and inhibitors of the kallikrein kinin system indicate that activation of these proteases occur during hypotensive gram-negative septicemia and adult respiratory distress syndrome. Using animal models of septicemia, we demonstrated that protease inhibitors or neutralizing monoclonal antibodies to proteins of the contact system inhibit or prevent the formation of kallikrein and the decrease in kininogen. In addition, the irreversible phase of hypotension can be prevented and survival prolonged. Thus, bradykinin is one of the important mediators of hypotension. In contrast, the contact system plays little role in the associated DIC. In cardiopulmonary bypass, the formation of kallikrein leads to neutrophil degranulation and release of elastase. Selective inhibitors of kallikrein not only block its activation but play a predominant role in inhibiting elastase release. PMID- 8356920 TI - The kinin system in inflammation. AB - Bradykinin and related kinins are important mediators of most kinds of inflammation. Mechanisms of kinin production in injury, infection and immune system activation are discussed. Bradykinin antagonists show great promise for development of new drugs for inflammation. PMID- 8356922 TI - Kinin antagonists as human therapeutics. PMID- 8356921 TI - Role of bradykinin in microbial infection: enhancement of septicemia by microbial proteases and kinin. AB - Data presented herein will show that bradykinin, microbial proteases which activate the kinin generating cascade, and kininase inhibitors can enhance septicemia by approximately 10 to 100 fold in mice infected intraperitoneally (i.p.) with a strain of bacteria, Pseudomonas aeruginosa 621, which does not usually produce a kinin generating protease. Bacterial spreading was evaluated either in the blood or in the spleen by colony formation on agar plates. Using the P. aeruginosa kaguma strain which produces a large amount of proteases, further experiments were carried out. Results showed that two different protease inhibitors (ovomacroglobulin and a synthetic peptide inhibitor against pseudomonal elastase) as well as a kinin antagonist suppressed bacterial dissemination to 1/10-1/100 of control. Similar results were observed in experiments using Vibrio vulnificus. These data support the hypothesis that microbial proteases and especially bradykinin is responsible for facilitation of microbial dissemination in vivo. PMID- 8356923 TI - Cytokine regulation of endothelial cell extracellular proteolysis. AB - The vascular endothelium plays a central role in the regulation of extrinsic fibrinolysis and thus maintains vascular patency through clot dissolution. Plasminogen activation provides an important source of localized proteolytic activity not only during fibrinolysis but also during a variety of other physiological and pathological processes. Numerous studies have indicated that human endothelial cells can directly synthesize and secrete plasminogen activators (PA) and inhibitors of these activators. PAs specifically hydrolyse a single arginine-valine bond in plasminogen, an abundant and widely distributed plasma zymogen, to form the broad spectrum serine protease, plasmin. Tissue type PA (t-PA) and urokinase type PA (u-PA) forms of PA have been described in endothelial cells, although t-PA production and secretion is elevated most frequently. The tPA form of PA functions predominantly in endothelial cell mediated fibrinolysis, while uPA is involved in tissue remodeling. During inflammatory reactions activated mononuclear phagocytes produce a variety of cytokines which may influence the phenotype of the endothelium through a process termed "endothelial cell activation". Tumor necrosis factor alpha (TNF alpha), a mononuclear cytokine, is a distinct polypeptide of Mr 17,000 and has been implicated as a mediator of gram negative induced sepsis as well as angiogenesis. TNF alpha is known to interact with specific endothelial cell receptors and to alter endothelial coagulant and anticoagulant properties implying that cytokines may be potent modulators of hemostasis. Recent observations have indicated that TNF alpha and lymphotoxin (TNF beta) can promote the expression, synthesis and secretion of urokinase plasminogen activator (uPA) in human endothelial cells. The upregulation of uPA results in an alteration in the fibrinolytic capacity of endothelial cells and allows cells the selective ability to degrade and invade underlying subendothelial extracellular matrix (ECM). Endothelial cells treated with TNF alpha also display, in an in vitro angiogenic assay, the ability to invade Matrigel and reorganize into tube-like structures, unlike control cultures. The effects of TNF alpha on the PA proteolytic system of endothelial cells, the biological significance of this event and potential in vivo consequences will be discussed. In addition, the influence of cytokine regulatory control systems will be described, since it is becoming increasingly clear that cytokines do not act in isolation. The vascular endothelium serves as a widely distributed anatomical interface between the blood and tissue with diverse capabilities, performing distinctive biologic functions at different sites and within specific organs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8356924 TI - Biochemical mechanisms for disrupting the proteinase-proteinase inhibitor balance in tissues. AB - The regulation of proteolytic activity in tissues by members of the Serpin family of inhibitors is normally tightly controlled. However, numerous mechanisms are available for interrupting this process in pathological tissues by depleting functional inhibitory activity at inflammatory foci. These include a) saturation of inhibitory activity due to excessive proteinase release from inflammatory cells, b) oxidative inactivation of inhibitory activity, c) proteolytic inactivation of inhibitory activity by non-complexing proteinases. In an attempt to regain a normal inhibitor-proteinase balance, however, it is now known that both inhibitor: enzyme complexes and inactive forms of inhibitors can act as signalling agents for the resynthesis of functionally active proteins. Thus, during inflammatory episodes where the levels of functional inhibitors are continually being depleted, mechanisms are in place to signal either directly or indirectly for their resynthesis. PMID- 8356925 TI - Different functional share of individual lysosomal cathepsins in normal and pathological conditions. PMID- 8356926 TI - Neuropeptide processing in pathophysiology. AB - Neuropeptides (peptides synthesized and secreted by neurons) perform many functions in the central nervous system as neurotransmitters, neuromodulators and neurotrophic factors. Neuropeptides are important regulators of amine neurotransmitter release, and can be identified as playing important roles in several pathological states. Neuropeptides are synthesized as protein precursors that are processed enzymatically to yield the biologically active peptides. Many neuropeptides having defined roles are further processed enzymatically to yield fragments having totally different actions. Examples discussed are substance P, adrenocorticotrophic hormone, endorphins and vasopressin. PMID- 8356927 TI - Endotoxin and eicosanoids. PMID- 8356928 TI - Oxidants, metalloproteases and serine proteases in inflammation. PMID- 8356929 TI - Proteases--structures, mechanism and inhibitors. AB - Proteases have been divided into four mechanistic classes: serine proteases, metalloproteases, aspartic proteases, and cysteine proteases. Once a new enzyme is classified by the use of general inhibitors, it is possible to design reactive inhibitors by using mechanistic information learned through study of other members of the same protease family. The most useful types of inhibitors for serine proteases are transition-state inhibitors including alpha-ketoesters and phosphonates, and mechanism-based inhibitors such as heterocyclic isocoumarin inhibitors. Some of these inhibitors are quite specific toward individual target serine proteases. Many proteases are involved in various disease states, and potent inhibitors of these enzymes have the potential to be developed as new therapeutic agents. In the future, it is likely than numberous specific protease inhibitors will be tested clinically for the treatment of human disease. PMID- 8356930 TI - Elastase and oxygen radicals: synergistic interactions. PMID- 8356931 TI - Proteolysis-induced pathomechanisms in acute inflammation and related therapeutic approaches. PMID- 8356932 TI - Synthesis and characterization of human neutrophil elastase inhibitors derived from aromatic esters of phenylalkanoic acids. PMID- 8356933 TI - In vivo evaluation of MDL 201,404YA, a novel inhibitor of human neutrophil elastase. AB - MDL 201,404YA (alternatively, CE-1037), a potent selective inhibitor of human neutrophil elastase (HNE), was tested both intratracheally and intravenously for its activity at inhibiting HNE. MDL 201,404YA given either i.t. or i.v. was effective in preventing the pulmonary hemorrhage which occurred after intratracheal instillation of HNE. Additional studies with MDL 201,404YA suggested that this compound remained active in the lung environment for at least 6 hours. Further evaluation of MDL 201,404YA suggested that it could inhibit the ongoing proteolysis caused by HNE when given 15 minutes after the initial HNE challenge. These data suggest that MDL 201,404YA may be effective therapeutically in treating conditions which result from an imbalance between elastase and its endogenous inhibitor alpha-1-proteinase inhibitor (alpha 1-PI). PMID- 8356934 TI - Alpha 1-antitrypsin augmentation therapy. AB - Alpha 1-proteinase inhibitor (also known as alpha 1-antitrypsin) derived from pooled human serum (Prolastin, Miles Biologicals) has been available in the United States since 1988. Although no formal controlled prospective study has been performed to prove its efficacy, intravenous administration of Prolastin has been the accepted treatment for individuals with pulmonary emphysema due to alpha 1-antitrypsin deficiency. In addition, Prolastin has been used experimentally by inhalation for the treatment of cystic fibrosis. It has been administered with some success to treat the panniculitis associated with alpha 1-antitrypsin deficiency. As a greater number of severely impaired alpha 1-antitrypsin deficient patients receive lung transplantation, the role of Prolastin in the post-transplant therapy of these patients will need evaluation. Newer antiproteases may render Prolastin obsolete with respect to its route of administration and its pricing, however, the safety record of this drug has been impressive. PMID- 8356935 TI - Covalent-binding native blot in the determination of specific IgE to latex gloves allergens. Comparison with other methods. AB - Six sera from patients with clinical symptoms of latex hypersensitivity and latex RAST values ranging from class 1 to 4 were used to characterize latex-glove allergens by immunoblotting. Twelve % acrylamide-SDS-PAGE of the latex glove crude extract revealed a single band with an estimated mol wt lower than 14,000 D. The proteins bound to nitrocellulose after electrical transfer as shown by Ponceau red staining of the membrane. However, standard immunoblotting methods using alkaline-phosphatase anti-IgE did not detect the presence of specific IgE. Different variants of SDS-PAGE immunoblotting were also unsuccessful. On the other hand, the use of IEF and capillary transfer (native blot) to a covalent binding hydrophilic membrane was found to be the method of choice for the study of this allergen. The authors believe that this procedure can be helpful in the study of other antigen-antibody systems, particularly when standard immunoblotting assays fail. PMID- 8356936 TI - Deflazacort in the treatment of uveitis: a comparative study versus prednisone. AB - Since corticosteroids represent a fundamental tool in the treatment of uveitis, we evaluate the clinical efficacy and possible appearance of side effects of deflazacort, a new corticosteroid of third generation, versus prednisone at equiactive dosages. Sixty six patients suffering from recurring acute anterior uveitis (RAAU) and/or chronic anterior uveitis (CAU) were treated with deflazacort or alternatively prednisone in an "open" study. Clinical efficacy, ophthalmological parameters and haemato-bioassays were evaluated on admission and during the treatment period. All patients showed a complete remission of clinical signs and symptoms with both treatment and no statistically significant difference was evidenced between the studied groups. Concerning the possible appearance of side effects, the comparison between deflazacort and prednisone a statistically significant difference. These preliminary results are strongly encouraging and suggest further controlled studies on the employment of deflazacort in the treatment of uveitis. PMID- 8356937 TI - Nutrition and immunity: where are we standing? PMID- 8356938 TI - Relationship of blood EG2+ eosinophils in patients with bronchial asthma. AB - The presence of eosinophils in peripheral blood has been previously associated with different degrees of activity in the evolution of disease in asthmatics. The eosinophil cationic protein is a mediator released by the eosinophils when they are activated due to various stimuli. The monoclonal antibody EG2 binds to human ECP, the epitopes which EG2 recognizes is only present in the secreted form of ECP, hence it only stains eosinophils which are undergoing activation and/or secretion. Flow cytometry was used to measure the level of eosinophils stained by the monoclonal antibody EG2 (eosinophil EG2+) in the peripheral blood of subjects with unstable extrinsic bronchial asthma, stable extrinsic bronchial asthma and healthy control group. A statistically significant higher level of eosinophil EG2+ was found in the group with unstable asthma than in either the group with stable asthma or the group of healthy subjects (p < 0.0002). No difference was found between the patients with stable asthma and the control group. The level of eosinophil EG2+ in peripheral blood, measured by flow cytometry, could be used as an indicator of inflammatory activity in patients suffering from bronchial asthma. PMID- 8356939 TI - Hyperaggregation of platelets detected by whole blood platelet aggregometry in newly diagnosed noninsulin-dependent diabetes mellitus. AB - Twenty-five newly diagnosed cases of noninsulin-dependent diabetes mellitus were studied at the time of diagnosis and again after metabolic control of diabetes was achieved (approximately 3 months later) for platelet aggregation abnormalities in whole blood by the impedance method. Adenosine diphosphate in 10 and 20 mumol/L final concentrations and arachidonic acid in 25 and 50 mmol/L final concentrations were used as agonists. Patients had a significant hyperaggregation of platelets (P < 0.01) at the time of diagnosis compared with age-matched healthy control subjects. After metabolic control of blood glucose was achieved using oral hypoglycemic agents (n = 20) and diet regulation alone (n = 5), there was a significant decrease in platelet aggregation (P < 0.01). There was a positive relationship between blood glucose levels and whole blood platelet aggregation with adenosine diphosphate (P < 0.02 and < 0.05, with 10 mumol/L and 20 mumol/L, respectively), but there was no relationship between aggregation and glycosylated hemoglobin levels. Thus, platelet hyperaggregation was present even at the time of diagnosis in patients with diabetes mellitus in the absence of any vascular complications, and there was significant improvement in platelet hyperaggregation after metabolic control of blood glucose levels was achieved. PMID- 8356940 TI - Artifactual prolongation of the activated partial thromboplastin time mimicking a coagulopathy. A lesson relearned. AB - A markedly prolonged activated partial thromboplastin time (APTT) was observed in a 61-year-old woman with bruising and a decreasing hematocrit. Coagulation laboratory evaluation was sought to determine the cause of the prolonged APTT and bleeding. Evaluation demonstrated that, rather than identifying a coagulopathy, the APTT prolongation was most likely artifactual. The APTT was actually very short. With a combination of a relatively strong activating APTT reagent (Dade Actin; Dade, Miami, FL) and a fixed lag phase in the automated coagulation instrument (16 seconds), the clot formed before the instrument began to read. Thus, during the period of observation (120 seconds), no change in optical density was observed. This was interpreted by the laboratory as "> 120 seconds." This case reminds those involved in the performance and interpretation of APTTs of the importance of a manual or visual method of verifying markedly prolonged APTTs. PMID- 8356941 TI - Reference ranges for lymphocyte subsets in pediatric patients. AB - Peripheral blood lymphocyte subset reference ranges were examined in a large group (N = 130) of healthy pediatric patients ranging in age from 1 month to 17 years. All samples were stained with monoclonal antibodies, processed with a whole blood lysis technique, and analyzed on a flow cytometer. Data analysis demonstrated statistically significant changes in most lymphocyte subsets at age 3 years. The relative and absolute numbers of total lymphocytes, CD2, CD4, and CD19 cells; absolute numbers of CD3 and CD8 cells; and CD4/CD8 ratios were high at birth, decreased during early childhood, and closely approximated adult reference values after age 3 years. The relative numbers of CD8 lymphocytes were low in early childhood and then rose to adult values after 3 years of age. The relative percentage of CD3 cells remained stable over all ages studied. Although "adult" lymphocyte subset reference ranges may be similar to those in children older than 3 years, age-adjusted reference ranges should be used for the early childhood period. PMID- 8356942 TI - Higher white blood cell counts and band forms in newborns delivered vaginally compared with those delivered by cesarean section. AB - The authors retrospectively reviewed complete blood counts in the medical records of all babies admitted to a normal newborn nursery from January through December 1989. The subjects consisted of 326 babies who were delivered vaginally (VgD) and 138 who were delivered by Cesarean section (CS). All blood samples were drawn by warmed or unwarmed heel sticks or by venipuncture. The subject's age at the time of blood drawing was similar in both VgD and CS groups (13.4 vs. 13.9 hours, P = 0.51). The number of total leukocytes, neutrophils, band forms, and platelets was significantly higher in VgD newborns than in CS newborns. The mean and standard error of the mean for each of these blood counts (each per microliter) were 23.9 x 10(9) +/- 0.33 versus 21.1 x 10(9) +/- 0.6, 14.6 x 10(9) +/- 0.26 versus 12.8 x 10(9) +/- 0.39, 1.18 x 10(9) +/- 0.08 versus 0.82 x 10(9) +/- 0.08, and 304 x 10(9) +/- 4.1 versus 286 x 10(9) +/- 0.6, respectively (P values for the first three comparisons were all less than 0.005). However, there was no difference between the two groups with regard to hemoglobin, hematocrit, and absolute number of lymphocytes, eosinophils, basophils, and monocytes (P > 0.5). It was speculated that the higher leukocyte, neutrophil, and band counts in VgD babies are the consequences of physical stress and periodic hypoxia, which are more frequent and prolonged with VgD compared with CS delivery. The authors suggest that the mode of delivery should be considered when interpreting blood counts in neonates. PMID- 8356943 TI - Diagnosis of hereditary spherocytosis with dual-angle differential light scattering. AB - Efficacy in the diagnosis of hereditary spherocytosis (HS) using a system of dual angle differential light scattering of a monochromatic laser beam on sphere shaped and fixed erythrocytes was evaluated. Fifty-one nonsplenectomized patients with HS, 6 with autoimmune hemolytic anemia, and 140 control subjects were studied. The percentage of erythrocytes with hemoglobin concentration more than 410 g/L (hyperhemoglobin) was significantly different in patients with HS and control subjects (P < 0.001). Hyperhemoglobin could be detected even in the mildest HS, in all patients with autoimmune hemolytic anemia, and in some control subjects, although none of the latter had more than 3%. This technique is extremely sensitive to the presence of spherocytes and the absence of erythrocytes with more than 410 g/L hemoglobin excludes HS. The presence of hyperhemoglobin is not specific for HS and increased amounts of hyperhemoglobin were found in patients with autoimmune hemolytic anemia and control subjects. To make a confident diagnosis of HS, the detection of hyperhemoglobin must be evaluated in the same clinical setting and with the same criteria as those applied to the osmotic fragility test. PMID- 8356944 TI - An evaluation of hemoglobin determination using sodium lauryl sulfate. AB - The standard reference method for hemoglobin determination for years has been the photometric quantitation of cyanmethemoglobin. Other existing methods have not gained popularity in North America. In an attempt to eliminate hazardous cyanide waste, a method to determine the hemoglobin concentration in whole blood using sodium lauryl sulfate has been devised and recently was released as a commercial reagent. The authors compare this new method with the cyanmethemoglobin method using two hematology analyzers. Their results show that there is excellent correlation between the two methods (r2 = 0.996). In addition, other elements of the complete blood count also show good correlation. Thus, it was confirmed that the sodium lauryl sulfate method of estimating hemoglobin concentration is an appropriate alternative to the cyanmethemoglobin method and avoids the generation of toxic wastes. PMID- 8356945 TI - Comparison of the HemoCue beta-glucose photometer and reflotron for open heart surgery. AB - The HemoCue beta-glucose photometer (Angelholm, Sweden) was evaluated for use in monitoring blood glucose in both diabetic and nondiabetic patients undergoing open heart surgery. Because occasional discrepancies were noted in patients with low total proteins when the Reflotron (Boehringer Mannheim, Indianapolis, IN) was used for this purpose, the effects of protein and hematocrit on glucose results from both instruments were investigated and compared with plasma values from a Paramax 720 ZX (Baxter Healthcare, Irvine, CA). Linear-regression analysis of the HemoCue results (y) versus Paramax (x) yielded y = 0.956x + 0.35, r2 = 0.980, with Sy/x = 0.57 mmol/L (10.3 mg/dL). Results from the Reflotron (y) versus Paramax (x) yielded y = 1.075x - 0.10, r2 = 0.964, with Sy/x = 0.99 mmol/L (17.8 mg/dL). Bias plots of (HemoCue-Paramax) or (Reflotron-Paramax) versus glucose, hematocrit, or protein showed no effect of glucose on the results from either instrument and no effect of protein or hematocrit on the HemoCue findings. The Reflotron, however, showed a positive bias of up to 3.5 mmol/L (63 mg/dL) at protein concentrations between 30-40 g/L (3.0-4.0 g/dL) and a possible positive bias at low hematocrit levels. PMID- 8356946 TI - Tumoral presentation of amyloidosis (amyloidomas) in soft tissues. A report of 14 cases. AB - Amyloidosis in its diverse types (immunocytic dyscrasia-associated, reactive, or heredofamilial) most often presents in a systemic form. Localized amyloidosis is uncommon in general and is exceedingly rare in the soft tissues. The authors discuss the cases of 14 patients in whom amyloidosis manifested as a localized mass ("amyloidoma") in the soft tissues (mostly mediastinal and retroperitoneal), leading to a clinical diagnosis of neoplasm in most cases. On the basis of the associated morphologically atypical and phenotypically monoclonal cell population, the resistance to potassium permanganate pretreatment, and the lack of reactivity with anti-AA antisera, 10 cases could be classified as immunocytic dyscrasia-associated AL-amyloidosis. However, four cases had histopathologic and histo- and immunohistochemical characteristics of reactive ("secondary") AA amyloidosis. This proportion (28.5%) was higher than that suggested by the sporadic AA-amyloidomas reported in the literature. The pathologic distinction between these two categories is important because patients with AA-amyloidomas of the soft tissues appear to have a better prognosis. PMID- 8356948 TI - Bednar tumor pattern in recurring giant cell fibroblastoma. AB - Giant cell fibroblastoma (GCF) and Bednar tumor (BT) have been perceived as two rare, not directly related, soft tissue neoplasms. Recent studies, separately conducted on each process, have presented evidence indicating that, in each instance, the tumor seemed to be related to the dermatofibrosarcoma protuberans. The case being reported provides additional evidence supporting those previous results and, for the first time, documents a direct link between GCF and BT, as seen in this girl who had a vulvar GCF resected at 1-year of age, with recurrence, 1.5 years later, as a mixed BT-GCF. PMID- 8356947 TI - Myocarditis associated with doxorubicin cardiotoxicity. AB - In contrast to previous reports, the authors were impressed by the frequency of myocarditis in the endomyocardial biopsy specimens of patients treated with anthracyclines. To examine this, they reviewed the histologic and electron microscopic results and immunoperoxidase stains of myocardial biopsy specimens from 11 patients with doxorubicin cardiotoxicity grades 1.0-3.0. Immunoperoxidase stains for lymphocytes, macrophages, and endothelial cells and induced expression of Class II antigen were performed using the avidin-biotin complex procedure. A full panel of monoclonal antibodies was employed on fresh-frozen tissue; a smaller panel was used with formaldehyde-fixed paraffin-embedded material. Four of the 11 endomyocardial biopsy specimens showed myocarditis, and 2 showed borderline myocarditis by the Dallas criteria. The infiltrating lymphocytes were generally characterized as T lymphocytes and were associated with induced Class II antigen expression by arterial endothelial cells. In addition, foci of replacement fibrosis, suggesting a chronic process, were identified. Although this association does not prove a causal relationship, these results suggest that myocarditis can be a component of doxorubicin-induced myocardial injury. PMID- 8356949 TI - Benign glandular schwannoma. AB - A rare example of a benign glandular schwannoma is reported. Further attention is drawn to this unusual subtype of schwannoma and the clinical parameters of the reported cases are compared with those of other types of schwannomas. The tumors tend to be small and superficial, and by contrast with malignant glandular schwannomas, the benign variant does not appear to be associated with von Recklinghausen neurofibromatosis. PMID- 8356950 TI - Cytologic diagnosis of metastatic epithelioid sarcoma. A cytologic mimic of squamous cell carcinoma. AB - A case of epithelioid sarcoma in a 39-year-old woman who had metastatic lesions in her lung from a primary arm tumor is presented. A review of the literature and analysis of this case did not identify any specific light microscopic or immunohistochemical way to separate definitively the lung cytologic smear in this case from squamous cell carcinoma. The authors believe cytologic smears from epithelioid sarcoma can closely mimic smears from squamous cell carcinoma. Pathologists should be alert to these similarities. PMID- 8356951 TI - The defective nature of hepatitis delta virus. PMID- 8356952 TI - Turnaround time, point-of-care testing, and a future role for the clinical pathologist. PMID- 8356953 TI - Tumoral amyloidosis of soft tissue (amyloidoma). New approaches to an old problem. PMID- 8356954 TI - Immediate management of mammographically detected breast lesions. PMID- 8356955 TI - Paradoxic effect of multiple mild coagulation factor deficiencies on the prothrombin time and activated partial thromboplastin time. AB - Single coagulation factor deficiencies predictably prolong the prothrombin time (PT) and activated partial thromboplastin time (APTT) at levels below 35% of normal activity. Acquired coagulopathies generally are characterized by multiple coagulation factor deficiencies. The effect was studied of such combined deficiencies on the PT/APTT using plasma from patients congenitally deficient in specific factors and pooled normal plasma. The PT begins to lengthen when individual factor levels fall below 25%. The APTT becomes prolonged when the levels of Factor V fall below 45%; the levels of Factors II and XI fall below 40%; and the levels of Factors I, V, VII, VIII, IX, and XII fall below 25% of normal. When plasma samples containing 50% activity of a single factor and 100% of all other factors were prepared by mixing the congenitally deficient plasma samples with the normal pool, the resulting mixtures had normal PT and APTT values. However, when two of these 50% factor-deficient plasmas were combined so that the mixture contained 75% activity of two coagulation factors and 100% of all other factors, the resulting PT and APTT were prolonged over the clotting times of either 50% factor-deficient plasma. Similar findings were obtained in patients with mild factor reductions caused by warfarin treatment. These data indicate that prolongations of the PT and APTT in disorders of coagulation affecting multiple factors represent less of a reduction in factor levels than is generally appreciated. This may explain the poor clinical correlation between abnormalities in these test results and clinical bleeding in acquired disorders of hemostasis. PMID- 8356956 TI - Behavior of diluted activated partial thromboplastin time in pregnant women with a lupus anticoagulant. AB - The present study was developed to verify whether a reduction in phospholipid concentration could increase the activated partial thromboplastin time (APTT) sensitivity to detect lupus anticoagulant (LA) during pregnancy. The authors studied 38 pregnant women (10 normal subjects and 28 patients with associated clinical complications) and 40 nonpregnant control subjects. Tests to detect LA, including APTT, platelet neutralization procedure (standard APTT), the kaolin clotting time, the diluted Russell viper venom test neutralized by lysed platelets, and factor assays, were performed. Positive results were found in 5 of 28 pregnant women with associated clinical complications. The APTT, using three different phospholipid concentrations (standard and more diluted cephalin), was performed on plasma samples and on its 1:1 mixture with normal plasma. The behavior of standard and diluted APTT was similar in negative LA pregnant women and nonpregnant control subjects. The mean values showed nonsignificant differences. Four of five pregnant women with positive LA findings had a prolonged APTT, which was not corrected by the addition of normal plasma using standard conditions. When diluted phospholipids were used, only one of them had a prolonged APTT that was corrected by the addition of normal plasma. Therefore, the highest sensitivity (80%) and specificity (100%) of the APTT to detect LA in pregnant women were obtained using the standard conditions. PMID- 8356957 TI - Selective screening for Chlamydia trachomatis infection in a primary care population of women. AB - The authors used cell cultures to assess the prevalence of cervical infection caused by Chlamydia trachomatis in a population-based sample of nonpregnant women aged 15 to 34 years who attended two primary care clinics at Group Health Cooperative of Puget Sound, Seattle, Washington, between January 1, 1988, and June 30, 1989. C. trachomatis was isolated from 67 of 1,804 women (3.7%), including 13% of those who were less than 20 years of age. Seven patient characteristics were independently predictive of chlamydial infection by stepwise multivariate logistic regression analysis: being unmarried, examination showing cervical ectopy, black race, douching, nulliparity, age of 24 years or less, and intercourse with two or more partners within the preceding year. Testing all women who had a score of 5 or more (28% of women) on a weighted index based on risk factors would detect 77% of all infections with a positive predictive value of 9%. These results suggest that it should be feasible to develop a risk factor based program to screen for cervical infection with C. trachomatis in populations where its prevalence is low. PMID- 8356958 TI - Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico. AB - Eosinophilia-myalgia syndrome (EMS) has been linked to ingestion of tryptophan contaminated with 1,1'-ethylidene-bis[L-tryptophan] (EBT), but other contaminants have received little study. The authors identified 101 lots of L-tryptophan that had been consumed either by persons with EMS or by asymptomatic tryptophan users and quantified the amounts of EBT and five other contaminants in each lot. After stratification of case and noncase lots by time of manufacture to adjust for the strong sequential pattern over time among case and noncase lots, higher EBT levels were still associated with a lot's case status, but the association lacked statistical significance (p = 0.120, odds ratio = 1.56, 95% confidence interval 0.758-3.23). While these findings do not rule out the possibility that EBT is the etiologic agent in EMS, they raise the possibility that other chemical contaminants in manufactured tryptophan modify the effects of EBT or that the causal agent of EMS is an entirely distinct compound. PMID- 8356959 TI - Relation between body size and bone mineral density in elderly men and women. AB - This cross-sectional study of the Rancho Bernardo, California, cohort examines the relation between bone mineral density and eight measures of body size (total weight, body mass index, waist-hip ratio, lean mass, fat mass, percentage fat mass, and current and maximum adult height) measured between 1988 and 1991 in 1,492 ambulatory white adults aged 55-84 years. Lean mass, fat mass, and percentage fat mass were measured by bioelectric impedance. Bone mineral density was measured at the hip and lumbar spine with dual-energy x-ray absorptiometry and at the midshaft and ultradistal radius with single photon absorptiometry. In multiple linear regression models adjusted for age, smoking, exercise, alcohol, thiazide use, and estrogen use (in women), total weight was the most consistent marker of bone mineral density overall. In this cohort, all measures of body size were associated with bone mineral density in both sexes and were better markers of bone mineral density in the weight-bearing sites than in the non-weight bearing sites, implying a mechanical effect of weight on bone mineral density. PMID- 8356960 TI - Estimating the population prevalence of injection drug use and infection with human immunodeficiency virus among injection drug users in Glasgow, Scotland. AB - Although data on the prevalence of injection drug use are an essential prerequisite for estimating the number of individuals infected with the human immunodeficiency virus (HIV), there have been few attempts to utilize statistical methods of population estimation based on multiple data sources. Data on 3,670 cases (2,866 individuals) were obtained from the HIV test register, drug treatment agencies, police records, and needle and syringe exchanges in Glasgow, Scotland, in 1990. Log-linear analysis was used to model the number of individuals in each of the sources. The model incorporating dependency among the three health care agencies (HIV test, drug treatment, and needle exchange) and independence of the police sample fitted the data well, with a residual chi 2 value of 2.9 (6 df). The expected value of the missing cell corresponding to absence from all four samples was 5,628, yielding an overall estimate of 8,494 injectors (95% confidence interval (CI) 7,491-9,721), for a prevalence rate of 1.35% for people aged 15-55 years in Glasgow during 1990. The high ratio of known to unknown injectors (1:2) resulted from the extensive coverage of known injectors and the relatively high level of overlap between the combined health care agency sample and the police sample. While further analysis demonstrated that the probability of appearing in the four samples varied by age and sex, heterogeneity in the population did not affect the choice of model or substantially alter the estimates for the total number of unknown injectors. A concurrent study of a community-wide sample of 503 injectors resulted in an HIV prevalence rate of 1.1% (95% CI 0.4-2.5%). The results of these studies were combined to produce a further estimate of 93 HIV-infected current injectors in Glasgow (95% CI 33-214). PMID- 8356961 TI - Efficacy of measles vaccines after controlling for exposure. AB - The clinical efficacy of measles vaccines was investigated in Niakhar, a rural area of Senegal under demographic surveillance in 1987-1990. Three measles vaccines were tested: a standard Schwarz, a high-titer Edmonston-Zagreb, and a high-titer Schwarz. The two high-titer vaccines were administered at 5 months of age and the standard Schwarz vaccine at 10 months. In addition to a formal randomized vaccine trial, data from national campaigns using the standard Schwarz vaccine were also analyzed. Clinical efficacy was estimated after controlling for exposure. In the randomized trial, the estimate of the efficacy of the standard Schwarz vaccine was 97.2% (95% confidence interval (CI) 91.3-98.1). In the 1986 1987 national campaign, the efficacy of the standard Schwarz vaccine was lower: 92.5% (95% CI 88.8-94.6). In the randomized trial, the efficacy of the high-titer vaccines was lower than that of the standard vaccine. High-titer vaccines were not used in national campaigns. Other factors associated with vaccine efficacy were age at exposure, intensity of exposure, and age at vaccination. Controlling for the intensity of exposure did not change the relative ranking of the efficacy of the three vaccination strategies. The theoretical efficacy of the standard measles vaccine for a single unit of exposure was estimated at 98.0%. PMID- 8356962 TI - Associations between changes in physical activity and risk factors for coronary heart disease in a community-based sample of men and women: the Stanford Five City Project. AB - Aerobic exercise training studies involving volunteers generally result in an improved cardiovascular risk factor profile. Little is known, however, about associations between physical activity change and risk factor change in a more representative sample, such as a community. This investigation evaluated correlations between a composite physical activity change score and change in cardiovascular risk factors from 1979 to 1985 in the cohort sample of the Stanford Five-City Project. Men (n = 380) and women (n = 427) between the ages of 18 and 74 years were evaluated for change in self-reported physical activity and change in total cholesterol, high density lipoprotein cholesterol (HDL cholesterol), systolic blood pressure, resting pulse rate, and body mass index (weight (kg)/height (m)2). For men, improvement in the composite physical activity score significantly correlated with an increase in HDL cholesterol (r = 0.14, p = 0.005) and decreases in body mass index (r = -0.16, p = 0.001) and estimated 10-year coronary heart disease risk score (r = -0.10, p = 0.056). For women, improvement in the physical activity score was associated with changes in HDL cholesterol (r = 0.11, p = 0.028) and resting pulse rate (r = -0.15, p = 0.001). These data demonstrate that an increase in physical activity over 5 years is favorably associated with changes in major cardiovascular disease risk factors in men and women and support the public health efficacy of community-wide promotion of physical activity. PMID- 8356963 TI - Dietary fat and sports activity as determinants for age at menarche. AB - A prospective study (1985-1991) was conducted to evaluate the role of nutrition, physical activity, and other life-style factors for the age at menarche, a known breast cancer risk factor. In 1988-1989, a total of 261 girls, aged 8-15 years, from a nationwide representative nutrition and activity survey (1985-1988) responded additionally to a mailed questionnaire on personal maturation and anthropometric data, physical activity, and information about nutritional habits, measured by a short food-frequency questionnaire. All girls without menarche at the time of questionnaire mailing were observed for 2 years or until the event of menarche. At the end of the follow-up period, 79% of the girls had experienced menarche. The survey and questionnaire data were analyzed for their relation to age at menarche using Cox's proportional hazards method. After excluding participants with largely deviating measurements between survey and questionnaire, the increased energy-adjusted fat intake was associated with accelerated menarche (relative risk = 2.1; 95% confidence interval 1.1-4.0; lowest vs. highest quartile), while increased sports activity was associated with a delay in menarche (relative risk = 0.3; 95% confidence interval 0.1-0.5; lowest vs. highest quartile). Parameters of physical development such as body weight or body fatness were found to be predictors of menarche. The study provides evidence that dietary effects on breast cancer risk might be indirect by influencing hormonal events like the age at menarche. PMID- 8356964 TI - Can men be trusted? A comparison of pregnancy histories reported by husbands and wives. AB - Agreement between pregnancies and pregnancy outcomes reported by husbands and wives was assessed in a sample of 857 couples interviewed between June 1989 and July 1990. The respondents were men employed in a semiconductor manufacturing plant in Burlington, Vermont, and their wives. The wives' reports were used as the standard against which the husbands' reproductive histories were evaluated. Measures included sensitivity, specificity, and percentage of agreement. Reports were considered to be congruent if an outcome reported by the husband agreed with the outcome reported by the wife within a period of +/- 6 months. Although men and women reported similar numbers of livebirths (1,478 and 1,500, respectively), men tended to misreport the timing of events; therefore, complete agreement on the numbers and dates of births was only 88.5%. Men also misreported the prevalence of low birth weight (sensitivity, 74%). Specificity was poorer for the younger (< 35 years) and less educated (< or = 12 years) respondents. Husbands' reports of spontaneous abortions had lower sensitivity (71.2%) than their reports of livebirths, particularly among the better educated (66.9%). Induced abortions were frequently omitted by the husbands (sensitivity, 35.1%), and events such as stillbirths or tubal pregnancies were too few in number to permit meaningful analysis. It is concluded that husbands' misreporting of their wives' reproductive histories may be substantial and sufficient to compromise the validity of epidemiologic studies. It would, therefore, be prudent to avoid the use of husbands as proxy informants of their wives' reproductive histories. PMID- 8356965 TI - Effect of fecal contamination on diarrheal illness rates in day-care centers. AB - Contact spread of enteropathogens in day-care centers is supported by the recovery (presence vs. absence) of fecal coliforms from hands and day-care center fomites. This prospective study was conducted to determine what, if any, quantitative measures of fecal coliforms predict the risk of diarrhea among day care center attendees. Diarrheal illness without concomitant respiratory symptoms was monitored among 221 children aged < 3 years in 37 classrooms (24 day-care centers) through biweekly parental telephone interviews from October 1988 to May 1989 in Cumberland County, North Carolina. The risk of diarrhea was expressed as new episodes/classroom-fortnight. Contamination was expressed as the log10 fecal coliform count per unit of surface area, per toy, and per child and staff hands. Significant predictors of diarrheal risk were any hand contamination (p = 0.003) and the number of contaminated moist sites (hands, faucets, and sinks) (p = 0.006). After adjusting for the child/staff ratio using weighted multiple regression, the authors found that classrooms with either any hand contamination (p = 0.0015) or contamination on all moist sites (p = 0.015) had a significant twofold increased rate of diarrhea compared with classrooms without contamination. This was the first study to demonstrate an increased risk of diarrhea associated with fecal contamination and the frequent sink contamination in day-care centers. PMID- 8356967 TI - Epidemiologic analysis of Kaposi's sarcoma as an early and later AIDS outcome in homosexual men. AB - The authors separately studied the epidemiology (risk and risk factors) of Kaposi's sarcoma occurring as an initial acquired immunodeficiency syndrome (AIDS) outcome (early Kaposi's sarcoma) and later after a different initial AIDS outcome (later Kaposi's sarcoma) in a cohort of 2,591 human immunodeficiency virus type 1-infected gay men of the Multicenter AIDS Cohort Study between 1984 and 1992. Among 844 AIDS cases, 202 presented with early Kaposi's sarcoma, 101 subsequently developed later Kaposi's sarcoma, and 541 were not diagnosed with Kaposi's sarcoma. Overall, 37.4% of AIDS cases were diagnosed with Kaposi's sarcoma prior to death. Kaposi's sarcoma diagnosed on the skin was significantly more common with early Kaposi's sarcoma (77.3%) than with later Kaposi's sarcoma (65.1%). Men presenting with an AIDS outcome other than Kaposi's sarcoma were at high risk for later Kaposi's sarcoma. Later Kaposi's sarcoma onset in men with a previous AIDS outcome was associated with the following characteristics: 1) lower immune status prior to AIDS and 2) longer post-AIDS survival. A Kaposi's sarcoma diagnosis in a man with a previous AIDS illness approximately doubled the risk (hazard) for death. Histories of urethral gonorrhea and scabies prior to study entry were more common in early Kaposi's sarcoma cases than in later Kaposi's sarcoma cases. However, self-reported sexual activity at study entry and prior to AIDS onset was highest in the later Kaposi's sarcoma group. In this cohort, cigarette smoking had a protective association against all Kaposi's sarcoma in univariate and multivariate models. Only 21.0% of the later Kaposi's sarcoma and 25.0% of the early Kaposi's sarcoma men smoked at least one-half pack of cigarettes daily at study entry compared with 33.8% of non-Kaposi's sarcoma and 35.5% of seroprevalent men still AIDS free. The reasons for this surprising association are unclear. However, other evidence which documents that habitual smoking alters the immune system (and possibly cytokine levels) in ways that could perhaps influence Kaposi's sarcoma pathogenesis should be considered. PMID- 8356966 TI - Composite risk score for Kaposi's sarcoma based on a case-control and longitudinal study in the Multicenter AIDS Cohort Study (MACS) population. AB - The possibility that an agent in addition to human immunodeficiency virus type 1 may be involved in the etiology of Kaposi's sarcoma in acquired immunodeficiency syndrome (AIDS) patients was investigated between 1984 and 1992 in this nested case-control analysis from the Multicenter AIDS Cohort Study (MACS) of homosexual and bisexual men. A total of 316 cases of Kaposi's sarcoma were identified and compared with 510 participants with AIDS and no evidence of cancer. More of the Kaposi's sarcoma cases were from Los Angeles and used a higher number of recreational drugs. The Kaposi's sarcoma cases were also more active sexually. There was a dose-response relation between Kaposi's sarcoma and the number of sexual partners, with an odds ratio of 2 between the most and least sexually active subgroups. The odds ratio for Kaposi's sarcoma increased to 4.18 (95% confidence interval 1.29-14.1) in the presence of a history of five infections. Hepatitis and gonorrhea contributed the most to this relation. The various observed odds ratios did not change after multivariate adjustment for the other risk factors. A model was developed combining all predictive associations into a composite risk score ranging from one to 12 and based on history of infections, sexual activity, use of poppers/nitrites, and having had sexual partners from the West Coast of the United States. The subgroup with the highest scores, compared to the subgroup with the lowest score, had an odds ratio of 8.93 (95% confidence interval 3.21-30.44) for Kaposi's sarcoma. A longitudinal proportional hazards analysis among all 2,190 human immunodeficiency virus type 1-seroprevalent men at study entry, based on this risk score and CD4 cells at baseline, confirmed these findings. Identifying these specific subgroups that are at high and low risk for Kaposi's sarcoma will help future investigations to be more focused in their search for an additional etiologic factor for Kaposi's sarcoma in AIDS. PMID- 8356968 TI - Sources of variability in waist and hip measurements in middle-aged women. AB - The reliability of single measurements of waist and hip circumference and the ratio of waist circumference to hip circumference (a widely used measure of body fat distribution) has not been fully examined. The authors analyzed measurements of waist and hip circumference, as well as self-reported weight and height, repeated 3-6 times between 1986 and 1991 among 1,851 participants in the New York University Women's Health Study. Quetelet index (weight (kg)/height (m)2) was positively correlated with waist circumference (r = 0.88), hip circumference (r = 0.89), and waist/hip ratio (r = 0.52). Mean weight was positively correlated with the within-subject variance of waist circumference (r = 0.27) and, to a lesser degree, with the within-subject variance of hip circumference (r = 0.08) and waist/hip ratio (r = 0.10). The within-subject variance of weight was positively correlated with the within-subject variance of waist (r = 0.30) and hip (r = 0.23) measurements, and less so with waist/hip ratio (r = 0.05). Intraclass correlations for waist, hip, and waist/hip ratio were 0.89, 0.81, and 0.74, respectively; adjustment for Quetelet index reduced the intraclass correlations for waist and hip measures by 33% and 48%, respectively. Such adjustment can provide a more realistic determination of the reliability associated with an exposure variable in the design and analysis of studies investigating the relation between body fat distribution and disease. PMID- 8356969 TI - Mortality-discriminating power of some nutritional, sociodemographic, and diarrheal disease indices. AB - This study compared the predictive power of selected nutritional (anthropometric), socioeconomic, and diarrheal disease morbidity variables for subsequent childhood mortality over a 1-year period. The data consisted of observations of approximately 1,900 children aged 6-36 months obtained from a longitudinal demographic surveillance system located in a rural area of Bangladesh in 1988-1990. The results suggested that weight-for-age (%) was the best predictor of subsequent mortality over a 1-year period, followed by weight velocity (monthly weight gain or loss in grams). Standardization of weight velocity by the US National Center for Health Statistics standard did not improve the mortality-discriminating power of this variable. Reported diarrheal morbidity was also a useful criterion for predicting mortality. Neither maternal education nor sex of the child had significant mortality-discriminating power. PMID- 8356970 TI - Malaria and low birth weight in central Sudan. AB - A nested case-control hospital study and a midwife-based community cohort study were conducted in Central Sudan during 1989 and 1990 to assess the contribution of mesoendemic malaria to low birth weight. Malarial infection was determined by maternal history, parasitology, and histopathology. There were significant associations between a maternal history of malaria and low birth weight in the hospital study (adjusted odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.2 2.1) and the community study (OR = 1.7, 95% CI 1.3-2.3). Attributable risk percentages were high and were comparable in the hospital study (22.2%) and the community study (24.5%). A significant trend of increased risk of low birth weight was observed with increasing number of reported malaria attacks, with attacks occurring earlier in pregnancy, and with higher parasitemia. In addition, the risk of low birth weight associated with malaria was higher among primiparous women than among multiparous women. The mean birth weight of infants whose mothers had malaria during pregnancy was significantly lower than the mean birth weight of infants whose mothers did not. Malaria treatment, chemoprophylaxis, and use of insecticides decreased the risk of low birth weight and are recommended as appropriate interventions. These measures should target primigravid women and should be initiated early in pregnancy. PMID- 8356971 TI - The bacterial etiology of conjunctivitis in early infancy. Eye Prophylaxis Study Group. AB - The authors conducted this study to determine the etiologic agents of conjunctivitis in early infancy. From 1985 to 1990, 630 infants enrolled in a randomized, controlled, double-masked study of eye prophylaxis were observed for 60 days after delivery for signs of conjunctivitis. The following isolates were categorized as pathogens: Haemophilus influenzae, Streptococcus pneumoniae, Neisseria cinerea, Klebsiella pneumoniae, and Chlamydia trachomatis. Using conditional logistic regression for analysis of 97 infant pairs, the authors identified isolates categorized as pathogens almost exclusively among cases (odds ratio (OR) = 18.0, 95% confidence interval (CI) 2.3-128). Among the microorganisms which have not usually been regarded as pathogens in the etiology of infant conjunctivitis, Streptococcus mitis was the only microorganism associated with an increased risk of conjunctivitis (OR = 5.3, 95% CI 1.8-15.0). The findings concerning the species of bacteria most often associated with conjunctivitis, as well as the finding that method of delivery is unimportant, suggest that bacteria were transmitted to the infants' eyes after birth and not from the birth canal. PMID- 8356972 TI - Day care attendance and other risk factors for invasive Haemophilus influenzae type b disease. AB - Two hundred and ninety-five of 373 (79%) children with reported cases of invasive Haemophilus influenzae type b (Hib) occurring in the state of Oklahoma from January 1, 1986, through December 31, 1987, were matched according to birth date with two controls each. Conditional logistic regression was used to assess the independent roles of day care attendance, number of young children in the home, crowding, passive smoking, maternal education, household income, and race in Hib disease. Statistically significant odds ratios (ORs) were found for day care attendance (OR = 2.9), the presence of two or more children in the home under 6 years of age (OR = 2.4), crowding (ratio of number of people in the home to number of bedrooms > or = 2) (OR = 2.0), and exposure to cigarette smoking in the home (OR = 1.4). Household income was independently associated with Hib disease. African Americans were at increased risk even after adjustment for income and crowding (OR = 4.1). Although there were no important differences in risk for other factors by type of Hib disease, there was a large and statistically significant difference in risk for day care attendance between meningitis (adjusted OR = 5.1, 95% confidence interval (CI) 3.1-8.2) and other types of Hib disease (combining nonmeningitis cases, adjusted OR = 1.6, 95% CI 0.9-2.7). Increasing numbers of hours per week of day care attendance and children per room were associated with increasing risk of Hib meningitis in a dose-response pattern. The highest day care ORs for meningitis were observed in the youngest (< 6 months) and oldest (> or = 24 months) children. The adjusted OR for exposure to breast feeding was 0.5 (95% CI 0.3-0.8). A protective effect for Hib polysaccharide vaccination among children aged > or = 18 months was suggested but did not reach statistical significance (OR = 0.4, 95% CI 0.2-1.1). PMID- 8356973 TI - Survival and mortality patterns of an acquired immunodeficiency syndrome (AIDS) cohort in New York State. AB - The survival experience and causes of death of acquired immunodeficiency syndrome (AIDS) patients were studied using a cohort of 3,699 AIDS patients in New York State, excluding New York City, whose illness was diagnosed before January 1990 at age 13 years or older. The median length of survival for all cases was 11.5 months, and survival increased over time from 5.3 months pre-1984 to 9.3 months in 1984-1986 and to 13.2 months in 1987-1989. In a Cox proportional hazards model, risk of dying was higher for persons aged 35 years or more at diagnosis and for persons with a diagnosis other than Pneumocystis carinii pneumonia or Kaposi's sarcoma whose illness was diagnosed before 1986. In this AIDS cohort, 2,834 (77 percent) persons died before 1991; 87 percent of the death certificates listed human immunodeficiency virus (HIV)/AIDS or an AIDS indicator disease as one of the multiple causes of death. The finding that 13 percent of the death certificates did not mention AIDS/HIV suggests that use of death certificates alone to count HIV-related deaths would result in an undercount. The recent expansion of the federal AIDS case definition is expected to add HIV-infected persons who die from conditions, such as recurrent pneumonia, that were not included in the earlier definition. PMID- 8356974 TI - Re: "Validity of exposure data derived from a structured questionnaire". PMID- 8356975 TI - Re: "Reproductive factors and risk of myocardial infarction". PMID- 8356976 TI - The American Society of Human Genetics 43rd annual meeting. New Orleans, Louisiana, October 5-9, 1993. Abstracts. PMID- 8356977 TI - Attempted cardiopulmonary resuscitation in nursing homes. PMID- 8356978 TI - Outcomes of cardiopulmonary resuscitation in nursing homes: can we predict who will benefit? AB - PURPOSE: To determine the benefits of cardiopulmonary resuscitation (CPR) in nursing home patients and assess possible prearrest and arrest predictors of survival. PATIENTS AND METHODS: During a 4-year period (1986 to 1989), consecutive nursing home patients from Milwaukee, Wisconsin, who sustained cardiac arrest and received CPR by paramedics were studied. The patients' prearrest clinical characteristics were determined including age, length of stay in nursing home, medical diagnoses, medications, circumstances surrounding the arrest, laboratory studies, and baseline functional status. Cardiac arrest data were obtained from a paramedic computer data base and included whether the arrest was witnessed, initial cardiac rhythm, and success of CPR. Survival was defined as the discharge of the patient alive from the hospital, and the patient's pre- and post-arrest functional status was compared. Possible predictors of survival were analyzed from the patient's prearrest characteristics and arrest characteristics. RESULTS: Of the total 196 patients who received CPR, 37 (19%) were successfully resuscitated and hospitalized, and 10 (5%) survived to be discharged. However, 27% of patients survived whose arrests were witnessed and who demonstrated ventricular fibrillation at the time of the arrest. In comparison, only 2.3% of all other nursing home patients who received CPR survived (p < 0.0002). Age, mental or functional status, hematocrit, renal dysfunction, pulmonary disease, cancer, and cardiovascular disease were not significant predictors of survival. At the time of hospital discharge, the functional status of the majority (80%) of the survivors was comparable to their prearrest status and 40% of the survivors lived for greater than 12 months. CONCLUSION: We conclude that only a small percentage of nursing home patients who sustain cardiac arrest will benefit from CPR. However, greater than 25% of nursing home patients whose arrest is witnessed and who demonstrate ventricular fibrillation will survive. This is comparable to the survival rate of elderly community-dwelling persons who sustain cardiac arrest. Our data suggest that CPR should be initiated only in nursing home patients whose cardiac arrest is witnessed and should only be continued in patients whose initial documented cardiac rhythm is ventricular fibrillation or ventricular tachycardia. PMID- 8356979 TI - Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women. AB - PURPOSE: To study the effect of exercise added to an energy-restrictive diet in overweight postmenopausal women. SUBJECTS AND METHODS: In a longitudinal clinical study, 121 healthy, overweight postmenopausal women (age 53.8 +/- 2.5 years, body mass index: 29.7 +/- 3.1 kg/m2) were randomly assigned to 3 groups: controls, a 4,200 kJ/d diet, or a 4,200 kJ/d diet with combined aerobic and anaerobic exercise. Body composition (measured by dual-energy x-ray absorptiometry), fat distribution, resting metabolic rate, blood pressure, serum lipids and lipoproteins, bone mineral densities, and markers of collagen and bone turnover were measured before and after 12 weeks of intervention. RESULTS: One hundred eighteen women completed the study. The mean loss of body weight (9.5 kg versus 10.3 kg, NS) was similar in the intervention groups, but compared with the diet only group, the diet-plus-exercise group lost more fat (7.8 kg versus 9.6 kg, p < 0.001) and no lean tissue mass (1.2 kg versus -0.0 kg, p < 0.001). The resting metabolic rate (per kg wt) was increased in the diet-plus-exercise group compared with the control group (11% versus 4%, p < 0.009). The levels of serum triglycerides, total cholesterol, low-density lipoprotein, and very-low-density lipoprotein decreased, and the ratio of high-density lipoprotein to low-density lipoprotein increased by 20% to 30% in both intervention groups compared with the control group (p < 0.001). The systolic blood pressure dropped, and the waist-to hip circumference ratio and abdominal-to-total body fat decreased in both intervention groups compared with the control group (10%, p < 0.003, and 3.5%, p < 0.0001). There were no consistent, major differences between the groups in terms of changes in total body, spinal, or forearm bone mineral densities, or in markers of collagen and bone turnover. CONCLUSION: Overweight postmenopausal women benefit from addition of combined aerobic and anaerobic exercise to an energy-restrictive diet. The diet itself has a positive effect on cardiovascular risk factors. PMID- 8356980 TI - Prophylaxis of urinary tract infection in persons with recent spinal cord injury: a prospective, randomized, double-blind, placebo-controlled study of trimethoprim sulfamethoxazole. AB - PURPOSE: To determine the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for prophylaxis of urinary tract infection in persons with recent spinal cord injury, during the first 4 months of intermittent catheterization. PATIENTS AND METHODS: One hundred twenty-nine adults (112 men, 17 women) with recent acute spinal cord injury participated in a randomized, double-blind, placebo-controlled trial, and were studied for up to 16 weeks. Low-dose TMP-SMX (TMP 40 mg, SMX 200 mg) or placebo was given once daily. Clinical observations, urine cultures, and cultures of rectal and urethral swabs were made weekly. Subjects who developed breakthrough bacteriuria received conventional antimicrobial therapy and prophylaxis was continued. RESULTS: Sixty-six TMP-SMX recipients (57 men, 9 women) and 60 placebo recipients (52 men, 8 women) are evaluable for efficacy. Among male subjects, bacteriuria was present during 50% or more of study weeks in 30% of TMP-SMX recipients and in 56% of placebo recipients (p = 0.003). The interval to the onset of bacteriuria was prolonged in TMP-SMX recipients (p < 0.0001). TMP-SMX recipients without bacteriuria in any given week had a lower probability of having bacteriuria the subsequent week (0.26) than did placebo recipients (0.49) (p < 0.0001). At least 1 episode of definite symptomatic bacteriuria (bacteriuria and fever and at least 1 classical manifestation of urinary infection) occurred in 4 of 57 TMP-SMX-treated men and in 18 of 52 placebo-treated men (p < 0.0003). We observed similar trends in women, but differences did not reach statistical significance, perhaps because the number of females was small. Adverse events suspected to be due to medications were frequent in this population of patients with recent severe injuries and led to discontinuation of the study in 10% of the TMP-SMX group and 8% of the placebo group. Adverse events included neutropenia (TMP-SMX: two; placebo: three), pseudomembranous colitis (TMP-SMX: one), severe skin rash (TMP-SMX: two; placebo: one), and drug fever (TMP-SMX: one). The proportion of all episodes of bacteriuria that were due to TMP-SMX-resistant organisms was unexpectedly high in the placebo group (51%), and increased progressively according to year of enrollment in the study. By Year 3, all subjects in the placebo group had at least one episode of TMP-SMX-resistant bacteriuria. Gram-negative enteric bacilli resistant to TMP-SMX were recovered from rectal swabs (TMP-SMX 49%, placebo 42%) and urethral swabs (TMP-SMX 33%, placebo 26%) in similar proportions of subjects in the two study groups. CONCLUSIONS: Prophylaxis with TMP-SMX significantly reduces bacteriuria and symptomatic urinary tract infection in persons with recent acute spinal cord injury during bladder retraining using intermittent catheterization. However, adverse reactions attributable to TMP-SMX are common in this population. Colonization and breakthrough bacteriuria with TMP-SMX-resistant organisms are frequent and may seriously limit the usefulness of this strategy, particularly in an institutional setting. PMID- 8356981 TI - Neuropsychiatric disease in Sjogren's syndrome: anti-ribosomal P and anti neuronal antibodies. AB - PURPOSE: Patients with Sjogren's syndrome (SS) may develop nonfocal (i.e., psychiatric and/or cognitive dysfunction) as well as focal, neuropsychiatric disease (CNS-SS). Anti-ribosomal P and anti-neuronal antibodies have been associated with nonfocal neuropsychiatric disease in systemic lupus erythematosus (SLE), particularly psychosis and depression. This study examines the spectrum of psychiatric and cognitive dysfunction observed in SS patients with focal, as well as nonfocal, central nervous system (CNS) disease and relates these observations to the presence of serum and cerebrospinal fluid (CSF) anti-ribosomal and anti neuronal antibodies. PATIENTS AND METHODS: One hundred thirty-one patients- patients with primary SS (n = 91), patients with secondary SS (n = 34), and mothers of infants with neonatal lupus erythematosus (NLE) (n = 6)--were studied. Patients were referred to a large tertiary referral center and the population was highly selected for CNS disease. Patients were evaluated clinically for focal and nonfocal CNS disease. Sera from 131 patients and 34 paired sera/CSF samples were examined by enzyme-linked immunosorbent assay and radioimmunoassay for the presence of anti-ribosomal P and anti-neuronal autoantibodies, respectively. Clinical features were categorized and autoantibody profiles obtained and correlated independently for statistical significance. Data were analyzed using the two-tailed Fisher exact test. RESULTS: Psychiatric or cognitive impairment, usually mild or moderate, occurred in over 80% (63 of 77) of this highly selected population of SS patients, and more than 60% of patients (48 of 77) had both. Anti-ribosomal P antibodies occurred in six (4.6%) patients with SS and related disorders. None of the patients with primary SS had anti-ribosomal P antibodies, whereas they were present in a small number of patients with secondary SS (i.e., 4 of 34 [12%]) and in 2 of 6 mothers of infants with NLE. There was no correlation between nonfocal CNS disease, including psychosis or severe depression, and the presence of anti-ribosomal P antibodies. Paired serum CSF samples from 34 SS patients with active CNS disease, including 6 with psychosis and 5 with severe depression, did not contain either anti-ribosomal P or anti neuronal antibodies. Anti-ribosomal P and anti-neuronal antibodies were present in a control subset of SLE patients defined serologically by the presence of anti nDNA antibodies. CONCLUSION: Patients with primary SS associated with CNS disease, including psychosis and depression, do not have serum or CSF autoantibodies to ribosomal P peptide or neuronal antigens, detected by binding to neuroblastoma cells. Thus, autoantibodies associated with nonfocal or diffuse CNS disease in classical SLE (particularly psychosis and depression) are not present in CNS-SS. The observations suggest that nonfocal CNS disease in CNS-SS and CNS-SLE may be mediated by different immunopathologic mechanisms. Potentially, these observations may have diagnostic and therapeutic implications in the management of patients with CNS-SS and patients with CNS-SLE. PMID- 8356982 TI - Autoimmune C1 inhibitor deficiency: report of eight patients. AB - PURPOSE: In this study, we investigated the clinical and biochemical features and the responses to treatment of eight patients with auto-antibody-mediated C1 inhibitor (C1-INH) deficiency and symptoms of angioedema. PATIENTS AND METHODS: In addition to the 8 patients with acquired angioedema (AAE), we also studied 36 subjects with hereditary angioedema (HAE), 15 of them treated with C1-INH plasma concentrate, and 26 patients with different autoantibodies in their plasma (10 with systemic lupus erythematosus, 6 with lupus-like anticoagulant, and 10 with chronic liver disease). Functional C1-INH was measured with the reagent kit of Immuno (Vienna, Austria); C1-INH, C4, and C1q antigen were determined by radial immunodiffusion; and autoantibodies to C1-INH were detected by an enzyme-linked immunosorbent assay method. RESULTS: Four patients with AAE had no other diseases, one had breast cancer, one liver hydatidosis, one Waldenstrom's disease, and one a benign M component. Functional C1-INH levels were below 30% of normal, and C1q plasma levels were low in seven patients but normal in one. Autoantibodies to C1-INH were detectable in all eight AAE patients but in none of the others. Prophylactic treatment with attenuated androgens was successful in one of four patients, and with antifibrinolytic agents (tranexamic acid) in six of seven patients. Laryngeal attacks in five patients were treated with C1-INH plasma concentrate; two patients had marked clinical and biochemical responses. In three, the symptoms resolved only with high doses, and the biochemical parameters did not significantly increase. CONCLUSIONS: Our results suggest that patients with autoimmune AAE are clinically and biochemically heterogeneous. They have different responses to treatment that seem to be related to variable C1-INH consumption. PMID- 8356983 TI - Primary hyperparathyroidism: incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy. AB - PURPOSE: This prospective study was designed to assess the effect of primary hyperparathyroidism on heart muscle, valves, and myocardial function. Echocardiography was used to evaluate changes in mechanical performance, the thickness of the left ventricular wall, myocardial calcific deposits, and valvular calcifications in patients with primary hyperparathyroidism. METHODS: Echocardiography was performed in 54 patients with hyperparathyroidism prior to surgery and 12 +/- 2 months after successful parathyroidectomy. A matched control group was followed for comparison. RESULTS: In a blinded fashion, aortic and mitral valve calcifications were detected in 63% and 49% of patients with primary hyperparathyroidism (controls: 12% and 15%, respectively). Calcific deposits in the myocardium were found in 69% of patients with hyperparathyroidism and 17% of the control subjects. After parathyroidectomy and 12 months of normocalcemia, a significant regression of left ventricular hypertrophy (p < 0.001) was observed. CONCLUSIONS: The present data show a high incidence of left ventricular hypertrophy, calcific deposits in the myocardium, and/or aortic and mitral valve calcification in patients with primary hyperparathyroidism. A 1-year follow-up after parathyroidectomy (and restoration of normocalcemia) discloses regression of hypertrophy, while calcifications persist without evidence of progression. PMID- 8356984 TI - Clinical characteristics of vasodepressor, cardioinhibitory, and mixed carotid sinus syndrome in the elderly. AB - PURPOSE: Carotid sinus syndrome (CSS) is frequently overlooked as a cause of syncope in the elderly. It is diagnosed when carotid sinus massage (CSM) produces asystole exceeding 3 seconds (cardioinhibitory CSS), a reduction in systolic blood pressure exceeding 50 mm Hg independent of heart rate slowing (vasodepressor CSS), or a combination of the two (mixed CSS). Most published data pertain to the cardioinhibitory subtype. The recent availability of noninvasive phasic blood pressure monitoring has allowed accurate routine assessment of the vasodepressor response to CSM. The aim of this study was to assess the clinical characteristics of vasodepressor, cardioinhibitory, and mixed CSS. PATIENTS AND METHODS: CSM was carried out on 132 consecutive patients over 65 years referred for investigation of dizziness, falls, or syncope. Massage was performed both supine and upright with continuous electrocardiographic and phasic blood pressure monitoring. Patients exhibiting greater than 1.5-second asystole were given 600 micrograms of intravenous atropine to abolish heart rate slowing and allow assessment of the pure vasodepressor response. RESULTS: Carotid sinus hypersensitivity was documented in 64 patients (mean age 81 +/- 7 years, 31 male). The response was vasodepressor in 37%, cardioinhibitory in 29%, and mixed in 34%. Thirty-six patients had recurrent syncope, 17 presented with unexplained falls, and the remainder had dizziness alone. Symptoms had been present for a median of 24 months, and the median number of syncopal episodes was four. Twenty five percent had sustained a fracture and, of these, 93% had not experienced a prodrome. Head movement precipitated symptoms in 47% and vagal stimuli in 73%. Episodes were unwitnessed in two thirds of patients. Twelve patients who presented with falls denied syncope but had witnessed loss of consciousness during CSM. Mean cardioinhibition was 5 +/- 2 seconds and mean vasodepression 61 +/- 9 mm Hg. The blood pressure nadir occurred rapidly at 18 +/- 3 seconds after massage, and baseline values were regained at 30 +/- 6 seconds. The clinical characteristics of patients with vasodepressor, cardioinhibitory, and mixed responses were similar. CONCLUSION: CSS is an underdiagnosed cause of dizziness, falls, and syncope in the elderly. The vasodepressor form occurs more frequently than previously reported and has clinical characteristics similar to those of the cardioinhibitory and mixed subtypes. Elderly patients with this condition may deny syncope and present with recurrent unexplained falls. CSM, ideally with noninvasive phasic blood pressure monitoring, should be routinely performed in elderly patients with unexplained bradycardic or hypotensive symptoms. PMID- 8356985 TI - Etiology of large pericardial effusions. AB - PURPOSE: To determine the effectiveness of the preoperative evaluation and overall diagnostic efficacy of subxiphoid pericardial biopsy with fluid drainage in patients with new, large pericardial effusions. DESIGN: A prospective interventional case series of consecutive patients admitted with new, large pericardial effusions. PATIENTS AND METHODS: Fifty-seven of 75 consecutive patients admitted to a university tertiary-care center and a university affiliated Veterans Administration Medical Center with new, large pericardial effusions were studied over a 20-month period. Each patient was assessed by a comprehensive preoperative evaluation followed by subxiphoid pericardiotomy. The patients' tissue and fluid samples were studied pathologically and cultured for aerobic and anaerobic bacteria, fungi, mycobacteria, mycoplasmas, and viruses. RESULTS: A diagnosis was made in 53 (93%) patients. The principle diagnoses consisted of malignancy in 13 (23%) patients; viral infection in 8 (14%) patients; radiation-induced inflammation in 8 (14%) patients; collagen-vascular disease in 7 (12%) patients; and uremia in 7 (12%) patients. No diagnosis was made in four (7%) patients. A variety of unexpected organisms were cultured from either pericardial fluid or tissue: cytomegalovirus (three), Mycoplasma pneumoniae (two), herpes simplex virus (one), Mycobacterium avium-intracellulare (one), and Mycobacterium chelonei (one). The pericardial fluid yielded a diagnosis in 15 (26%) patients, 11 of whom had malignant effusions. The examination of pericardial tissue was useful in the diagnosis of 13 (23%) patients, 8 of whom had an infectious agent cultured. Of the 57 patients undergoing surgery, the combined diagnostic yield from both fluid and tissue was 19 patients (33%). CONCLUSIONS: A systematic preoperative evaluation in conjunction with fluid and tissue analysis following subxiphoid pericardiotomy yields a diagnosis in the majority of patients with large pericardial effusions. This approach may also result in the culturing of "unusual" infectious organisms from pericardial tissue and fluid. PMID- 8356987 TI - Noninvasive monitoring. AB - Noninvasive monitors are finding increased use in the intensive care unit both as labor-saving tools and as a means to reduce complications associated with invasive techniques. The current technology allows for the replacement of a number of invasive devices with a noninvasive counterpart capable of providing similar information. The potential reduction in morbidity and mortality realized with a greater reliance on noninvasive monitors should result in widespread application of these modalities. PMID- 8356986 TI - Needle exchange decreases the prevalence of HIV-1 proviral DNA in returned syringes in New Haven, Connecticut. AB - PURPOSE: To report on the deployment of the syringe tracking and testing system in the New Haven needle exchange program, which is the first federally funded evaluation of a needle exchange program conducted in the United States. PATIENTS AND METHODS: A legal needle exchange for intravenous drug users began in New Haven, Connecticut, in November 1990. All syringes distributed by the program received unique tracking codes. Syringes were tracked and HIV-1 proviral DNA prevalence in returned syringes was assessed using polymerase chain reaction and Southern blotting. RESULTS: At the outset of the program, the prevalence of HIV-1 proviral DNA in syringes exceeded two thirds. Prevalence decreased rapidly to less than 45% during the first 3 months of the program and remained at this level for the following 10 months. During the periods of decreasing prevalence and subsequent steady state, no changes in the demographics of program participants or in the drug use habits of newly enrolling clients that could account for the decrease in HIV-1 prevalence in needles were detected. In addition, the program referred almost 20% of its clients to drug treatment programs. CONCLUSION: The needle exchange program in New Haven has decreased the percentage of syringes testing positive for HIV-1 proviral DNA among needle exchange clients while simultaneously serving as an entry point for drug treatment. PMID- 8356988 TI - Build it and they will come. PMID- 8356989 TI - Retooling academic internal medicine: the challenge to departmental leadership. PMID- 8356990 TI - Acute pulmonary coccidioidomycosis mimicking bacterial pneumonia and septic shock: a report of two cases. AB - Two patients with acute pulmonary coccidioidomycosis presenting as acute bacterial pneumonia and sepsis are described. One patient died despite appropriate antifungal therapy, whereas the diagnosis in the other patient was only established after postmortem examination. In both cases, coccidioidomycosis had disseminated beyond the lungs. Factors leading to overwhelming coccidioidomycosis are discussed, and the relation of the sepsis syndrome to coccidioidomycosis is reviewed. PMID- 8356991 TI - Coma due to ciguatera poisoning in Rhode Island. AB - A patient is presented who developed an acute gastrointestinal and neurologic syndrome progressing to coma after ingestion of a fish soup made in Rhode Island. Laboratory studies confirmed the clinical diagnosis of ciguatera poisoning. Physicians should be aware of the diagnostic features of this disease even in non endemic areas. PMID- 8356992 TI - Adrenal abscess as a complication of adrenal fine-needle biopsy. PMID- 8356993 TI - Didanosine-induced hypertriglyceridemia. PMID- 8356994 TI - Omeprazole-induced acute interstitial nephritis. PMID- 8356995 TI - Para-articular manifestations of palindromic arthritis. PMID- 8356996 TI - Continuing Developments with Nabumetone: An Investigators' Update. Proceedings of a symposium. PMID- 8356997 TI - Safety experience with nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in osteoarthritis and rheumatoid arthritis. AB - The comparative safety of nabumetone (1,000-2,000 mg/day) versus diclofenac (100 200 mg/day), naproxen (500-1,500 mg/day), piroxicam (10-20 mg/day), and ibuprofen (1,200-3,200 mg/day) was evaluated in a 12-week, randomized, open-label, multicenter study. Patients with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in a 3:1 ratio (nabumetone:one of the four comparator NSAIDs). The incidence of > or = 1 adverse event considered by the investigator to be related or probably related to therapy was similar in all groups. However, significantly (p < 0.02) more diclofenac-treated patients experienced abdominal pain and/or gastritis than nabumetone-treated patients. Naproxen-treated patients experienced significantly (p < 0.002) more dyspepsia as compared with patients treated with nabumetone or ibuprofen and significantly (p < or = 0.001) more nabumetone treated patients experienced diarrhea than patients treated with naproxen, ibuprofen, or piroxicam. Ulcers occurred in one (0.03%) nabumetone-treated patient versus six (0.5%) patients treated with one of the comparator NSAIDs (p = 0.001). A decrease in hemoglobin > or = 1.5 g/dL occurred in fewer nabumetone treated patients than in patients treated with diclofenac (p < 0.04), ibuprofen (p < or = 0.04), or piroxicam (p = 0.055). Finally, a similar percentage of patients in all treatment groups withdrew from the study because of adverse events related or probably related to treatment. More (p < 0.001) diclofenac treated patients withdrew because of elevated hepatic transaminases than patients treated with the other agents. Withdrawal because of gastritis was also noted for more diclofenac-treated patients than nabumetone-treated patients (p < 0.04). In conclusion, nabumetone was demonstrated to be at least as safe as diclofenac, piroxicam, ibuprofen, and naproxen as related to subjective complaints, such as dyspepsia or gastritis. However, more serious events, such as ulcers or meaningful decreases in hemoglobin, seem to occur less often with nabumetone. PMID- 8356998 TI - Efficacy and safety of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in the elderly. AB - In a randomized, open-label, controlled, multicenter, 12-week study, the efficacy and safety of nabumetone (1,000-2,000 mg/day) versus diclofenac (100-200 mg/day), naproxen (500-1,500 mg/day), ibuprofen (1,200-3,200 mg/day), or piroxicam (10-20 mg/day) were evaluated in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). The results in elderly patients (> or = 65 years of age) are presented. Nabumetone was as effective as the comparator nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of elderly OA and RA patients. Ibuprofen and diclofenac caused significantly (p < 0.05) more abdominal pain than nabumetone (8.5%, 13.1%, and 4.1%, respectively). The frequency of abdominal pain was dose related for all NSAIDs except nabumetone. Diarrhea was reported by significantly (p < 0.02) more nabumetone-treated (6.6%) than ibuprofen-treated (0.9%) elderly patients, but the incidence of diarrhea was not dose related. There were no clinically significant changes in renal function with nabumetone or the comparator NSAIDs. A significant change in hepatic enzymes occurred in elderly patients treated with diclofenac (3.3%), which was different than for patients treated with nabumetone (p < 0.04), naproxen (p < 0.06), or ibuprofen (p < 0.06). With regard to withdrawals for adverse events, more (p < 0.04) piroxicam treated patients (4.9%) withdrew than nabumetone-treated patients (1%). In addition, doubling the dose of nabumetone from 1,000 mg/day to 2,000 mg/day did not result in a proportional increase in adverse events. However, with the comparator NSAIDs, proportional increases in adverse events occurred with increased dose. Finally, the efficacy and safety of nabumetone in elderly patients were similar to the efficacy and safety observed in nonelderly patients. PMID- 8356999 TI - Efficacy of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in osteoarthritis and rheumatoid arthritis. AB - The efficacy of nabumetone was compared with that of diclofenac, naproxen, ibuprofen, and piroxicam in patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in a randomized, controlled, open-label, multicenter trial. Patients > or = 18 years with clinical and radiographic evidence of OA or RA (functional class I, II, or III), who provided written informed consent, were eligible. To mimic real-life therapy, no washout phase preceded randomization. Eligible patients were assigned in a 3:1 ratio to receive nabumetone or a comparator NSAID for 12 weeks. Thus a total of 4,411 eligible patients were randomized to receive nabumetone (N = 3,315) or one of the comparator NSAIDs (N = 1,096). Initial daily doses were: nabumetone, 1,000 mg; diclofenac, 100 mg; naproxen, 500 mg; ibuprofen, 1,200 mg; piroxicam, 10 mg. Dosage increases were permitted after a 2-week trial period. All patients were evaluated at baseline, and at 4 and 12 weeks. Of all patients randomized, approximately 46% had RA and approximately 54% had OA. Demographic characteristics were similar for the nabumetone and comparator NSAID treatment groups. In OA, nabumetone was as effective as the comparator NSAIDs in the physician and patient global assessments of disease activity, in improving the Activities and Lifestyle Index, and in decreasing the degree of pain. There was no significant difference in the percentage of patients withdrawn for lack of efficacy when treated with nabumetone or one of the comparator NSAIDs. In contrast, nabumetone was significantly (p < or = 0.02) more effective than the comparator NSAIDs in RA patients for the global assessments of disease activity, pain relief, and improving the Activities and Lifestyle Index, primarily due to the poor response in the ibuprofen and piroxicam treatment groups. Furthermore, fewer nabumetone treated RA patients (8.8%) withdrew for lack of efficacy than those treated with diclofenac (10.3%), naproxen (11%), piroxicam (13.5%), or ibuprofen (13.2%). In conclusion, in a large, randomized, open-label trial that mimicked real-life therapy, nabumetone was as effective as diclofenac, naproxen, piroxicam, and ibuprofen for the treatment of patients with OA. However, in RA, nabumetone was significantly more effective than the comparator NSAIDs, and fewer patients were withdrawn because of lack of efficacy. PMID- 8357000 TI - Nonsteroidal antiinflammatory drug use in patients receiving warfarin: emphasis on nabumetone. AB - Phenylbutazone has been clearly demonstrated to interact pharmacokinetically and clinically with warfarin, although several other nonsteroidal antiinflammatory drugs (NSAIDs) also have the potential to interact with warfarin to cause alterations in prothrombin time. Aspirin is known to inhibit platelet aggregation irreversibly, whereas nonaspirin NSAIDs are thought to inhibit platelet aggregation reversibly. In contrast, nabumetone was not shown to cause significant inhibition of platelet aggregation, which may be related to the fact that nabumetone preferentially inhibits the prostaglandin synthase-2 isozyme instead of the prostaglandin synthase-1 isozyme. Furthermore, in studies in patients and normal volunteers stabilized on warfarin, nabumetone did not cause alterations in the prothrombin time or international normalized ratio. Based on data evaluating the concomitant use of nabumetone and warfarin, the relative lack of platelet inhibition, and the relatively lower risk of nabumetone-induced gastrointestinal mucosal damage as assessed by radiolabeled chromium-51 fecal blood loss studies and endoscopic evaluations, nabumetone may be preferred if concomitant therapy with warfarin is indicated. PMID- 8357001 TI - Gastrointestinal damage demonstrated with nabumetone or etodolac in preclinical studies. AB - Nabumetone, a nonacidic, nonsteroidal antiinflammatory drug (NSAID), and etodolac, an acidic NSAID, were compared to assess the gastrointestinal (GI) tolerability of these agents and their effects on gastric prostaglandins in rats. In a single-dose study, etodolac caused a significant increase in both gastric and intestinal damage 6, 24, 48, and 144 hours after dosing. In contrast, no significant GI damage was noted with nabumetone. Chronic, 28-day studies comparing five times the ID25 (the dose that reduces carrageenan-induced inflammation by 25% in 50% of animals) of nabumetone with twice the ID25 of etodolac demonstrated a significant increase in both gastric and intestinal damage with etodolac, but no GI damage with nabumetone, despite the higher dose employed. In single-dose studies comparing gastric damage and prostaglandin synthesis 4 hours after dosing, both nabumetone and etodolac did not significantly reduce gastric prostaglandin I2 production. However, there was a significant increase in gastric damage with etodolac, but not with nabumetone. It was hypothesized, and confirmed in a second study, that there is a transient inhibition of gastric prostaglandin synthesis with etodolac that is responsible, in part, for the gastric damage noted. In conclusion, acute and chronic dosing of nabumetone at doses up to five times the ID25 did not cause GI damage in rats. In contrast, etodolac did result in GI damage, which is thought to be, in part, the result of a transient inhibition of gastric prostaglandin synthesis, observed at minimally effective antiinflammatory doses. PMID- 8357002 TI - PGH synthase isoenzyme selectivity: the potential for safer nonsteroidal antiinflammatory drugs. AB - With the recent cloning of a second gene coding for the prostaglandin endoperoxide (PGH) synthase (cyclooxygenase), it has become obvious that mammalian cells contain two related, but unique, isozymes of PGH synthase. Both of these isozymes catalyze the conversion of arachidonic acid to PGH2, leading to production of biologically active prostaglandins. Although the first of these isozymes, PGH synthase-1 (PGHS-1), has long been thought to be the primary and sole site of action of nonsteroidal antiinflammatory drugs (NSAIDs), it is now known that the second isozyme, PGH synthase-2 (PGHS-2), is also sensitive to NSAIDs. Cloning of complementary DNAs for murine PGHS-1 and PGHS-2 has permitted individual expression of these two isozymes in the cos-1 cell system and comparison of their relative inhibition by several common NSAIDs in vitro. These studies have demonstrated that the two mouse isozymes, PGHS-1 and PGHS-2, are pharmacologically distinct. PGHS-1 is a constitutively expressed enzyme that early observations indicate is the principal enzyme involved in producing prostaglandins that regulate cellular housekeeping functions, such as gastric cytoprotection, vascular homeostasis, and kidney function. In contrast, PGHS-2 appears only to be expressed in inflamed tissue or following exposure to growth factors, lymphokines, or other mediators of inflammation. Expression of PGHS-2 is inhibited by antiinflammatory glucocorticoids, lending further support to the hypothesis that this enzyme produces prostaglandins involved in inflammation. We have identified NSAIDs that preferentially inhibit murine PGHS-1 or PGHS-2 or inhibit both isozymes equally. The finding that the two isozymes can be differentially inhibited provides a possible mechanism for identifying safer, more effective NSAIDs. Screening for drugs that preferentially inhibit PGHS-2 may allow identification of NSAIDs that reduce inflammation, but spare renal and gastric prostaglandin synthesis, thus reducing the untoward side effects commonly associated with most NSAIDs. Thus far, nabumetone is the only NSAID identified that preferentially inhibits murine PGHS-2. PMID- 8357003 TI - Fronto-nasal dysostosis, callosal agenesis, crossed-fused ectopia, tibial hemimelia, and preaxial polydactyly of feet: severe expression of the acrocallosal syndrome? AB - We report on a girl with frontonasal "dysostosis," callosal agenesis, crossed fused ectopia, tibial hemimelia, and preaxial polydactyly of feet. This pattern of the developmental defects suggests a severe form of the acrocallosal syndrome. Implications for genetic counselling are discussed. PMID- 8357004 TI - New form of spondyloepimetaphyseal dysplasia (SEMD) in Jewish family of Iraqi origin. AB - We report a distinct type of spondyloepimetaphyseal dysplasia seen in 2 sibs and their second cousin, characterized by early onset severe short stature, small chest, and distended abdomen. They had short neck, severe lumbar lordosis, and marked genu varum due to fibular overgrowth and joint laxity. Radiographically, the patients had platyspondyly, initially noted during the first years of life, with central hypoplasia of the vertebral bodies. At a later age, the vertebrae appear squared with mild interpedicular narrowing. The long bone changes, which at early age resemble those seen in achondroplasia, later include general metaphyseal irregularities and significant epiphyseal ossification delay. These patients present a previously undescribed form of spondyloepimetaphyseal dysplasia, most probably transmitted as an autosomal recessive tract. PMID- 8357005 TI - Mental retardation locus in Xp21 chromosome microdeletion. AB - Xp21 microdeletion syndrome is associated with variable size Xp21 deletions that usually include the glycerol kinase locus. The clinical phenotypes we studied in this chromosome region include: Xpter - Aland Island eye disease (AIED) -adrenal hypoplasia (AH) -glycerol kinase (GKD) -Duchenne muscular dystrophy (DMD) retinitis pigmentosa (RP) -ornithine transcarbamylase (OTC) -centromere. In a compilation of 18 individuals in 14 families with the AH, GKD, and DMD loci deleted, 17 were male and all were developmentally delayed. In contrast, we report mentally retarded female carriers in two Xp21 deletion syndrome families with DMD, GKD, and AH in affected males. In the first family with normal karyotypes, a submicroscopic deletion was associated with DMD in the retarded male and with retardation in carrier females. In the second family an X chromosome with a cytogenetically deleted Xp21 distal to the OTC and RP genes segregated in the affected male and retarded female carriers. DNA analysis at the DMD locus verified the cytogenetic findings. This report of mental retardation in otherwise asymptomatic female carriers of Xp21 deletion classifies one form of mental retardation in females. PMID- 8357006 TI - Alopecia universalis as a single abnormality in an inbred Pakistani kindred. AB - A Pakistani kindred comprising 5 generations contained 9 males and 4 females with alopecia universalis as a single abnormality without any associated defects. The skin biopsy from the scalp showed hair follicles without hair. Analysis of the pedigree is strongly suggestive of autosomal recessive inheritance, and consanguineous loops could account for all affected persons being homozygous for the abnormal allele. PMID- 8357007 TI - Study of isolated apparent amniogenic limb deficiency in Hungary, 1975-1984. AB - A population-based and validated data set of 206 cases with apparent amniogenic limb deficiency was ascertained in Hungary between 1975 and 1984. Such limb defects frequently (36%) associated with nonlimb abnormalities. In 134 cases with isolated defects typically more limbs are affected, upper and lower limbs, right and left sides, and both sexes are equally affected. Case-control analysis of such isolated cases indicates a lower socioeconomic status of parents, a higher parity, more frequent unwanted pregnancies, preterm birth, and a higher rate of threatened abortion. Familial occurrence was not found in 415 first-degree relatives. PMID- 8357008 TI - Preaxial acrofacial dysostosis (Nager syndrome) associated with an inherited and apparently balanced X;9 translocation: prenatal and postnatal late replication studies. AB - We report on an infant with preaxial acrofacial dysostosis (Nager syndrome) who was diagnosed prenatally as having an apparently balanced X/autosome translocation [46,X,t(X;9)(p22.1;q32)mat] inherited from a previously diagnosed mosaic translocation carrier mother [46,XX/46,X,t(X;9)(p22.1;q32)]. Replication studies on amniocytes showed the normal X chromosome to be late replicating while the same studies repeated on the infant's lymphocytes showed the translocated X chromosome to be late replicating in most cells. Late replication studies of the mother's lymphocytes demonstrated that the normal X chromosome was late replicating in most cells. The presence of Nager syndrome in this infant may be the result of critical breakpoints and/or position effects on chromosome 9, inducing expression of a gene responsible for the syndrome. PMID- 8357009 TI - Isochromosome 18p in a mother and her child. AB - We present a familial case of isochromosome 18p [i(18p)] as a supernumerary chromosome. The mother, who is a mosaic for i(18p) with partial tetrasomy 18p syndrome, transmitted the isochromosome to her only child. The child has the full syndrome of tetrasomy 18p. This is the first case of mosaicism i(18p) in an adult patient with clinical manifestations. PMID- 8357010 TI - Pseudoaminopterin syndrome. AB - We report on a boy with a combination of manifestations reminiscent of aminopterin embryopathy: brachyturricephaly with craniosynostosis, poorly mineralised vault, upslanted palpebral fissures, malar hypoplasia, high-arched palate, micrognathia, thick, abnormal auricles, ASD, minor hand anomalies, growth and mental retardation. Three convincing cases of "Aminopterin Syndrome Sine Aminopterin" have been reported (the fourth case possibly having the Juberg Hayward syndrome). Variability and heterogeneity of cases with apparent aminopterin embryopathy are discussed. PMID- 8357011 TI - Cultural and psychosocial considerations in screening for thalassemia in the Southeast Asian refugee population. AB - The combination of a high incidence of thalassemia and a high fertility rate in the Southeast Asian refugee population mandates effective screening programs, but unique cultural and psychosocial factors often impede optimal screening and genetic counseling. This paper identifies cultural and psychosocial barriers often associated with refugee thalassemia screening, and offers practical guidelines for remediation. PMID- 8357012 TI - Hirsutism-skeletal dysplasia-mental retardation syndrome with abnormal face and a uric acid metabolism disorder. AB - We report on a German boy, born to nonconsanguineous parents, with an apparently new combination of multiple congenital anomalies including extraordinary hirsutism, marked brachycephaly, abnormal position of thumbs, pedes excavati with claw-toes, an abnormal face, and mental retardation. Additionally the boy manifests a disorder of uric acid metabolism. This sporadic case may represent a new syndrome due to a fresh autosomal or X-linked mutation, or chance-isolated case due to segregation of an autosomal recessive gene. PMID- 8357013 TI - Oral zinc therapy in the treatment of alpha-mannosidosis. AB - Human alpha-mannosidosis is a lysosomal storage disorder characterized by mental retardation, dysostosis multiplex, and hepatosplenomegaly. Deficiency of the enzyme leads to accumulation of mannose-rich glycoconjugates in tissues. Zinc sulphate has been shown to stimulate alpha-mannosidase activity in vitro. Oral zinc therapy was attempted on a 4-year-old boy with alpha-mannosidosis for 3 years. After almost 10 years of follow-up on and off zinc therapy, we must conclude that oral zinc does not substantially affect the clinical course of alpha-mannosidosis. PMID- 8357014 TI - Effect of fragile X on physical and intellectual traits estimated by pedigree analysis. AB - A maximum likelihood scoring technique for analysis of pedigree data, which allows for estimation of random effects (variance components) concurrently with other "fixed" effects in a quantitative trait, was applied to establish the effect of the fragile X condition in the variation of intellectual and physical traits. In 52 fragile X families, intellectual status was represented by measures of vocabulary knowledge (PPVT) and of nonverbal visuospatial skills (BDT), and physical status by a combined physical (anthropometric) score, and jaw length. The fixed effects included fragile X and sex and their interaction on the mean and covariances between relatives for the intellectual and physical scores. The random effects included environmental (common and individual) and genetic (additive and dominance) components. Different genetic models were tested by the likelihood ratio criterion, and the maximum likelihood parameters for each of the three scores were based on the most appropriate models. The effect of fragile X on the mean values was found to be significant for all the traits, and much more conspicuous in male than in female individuals, the effects in the PPVT and the anthropometric score being intercorrelated. The effect of fragile X on growth of a single physical trait relative to height was demonstrated using jaw length as an example. We have also demonstrated an effect of fragile X on genetic (additive) variance, as well as on the mean of the BDT score, and the effect of age on the nongenetic variance of PPVT, and jaw length. PMID- 8357015 TI - Pattern of cardiac malformation in oculoauriculovertebral spectrum. AB - The reported prevalence of congenital heart defects (CHD) in the oculoauriculovertebral "spectrum" (OAVS) is 5-58%. This variability is mainly due to differences in the diagnostic criteria used, and to ascertainment bias introduced by selection of patients from different specialty databases. Two thirds of the cardiac anomalies reported are either tetralogy of Fallot (TOF) or ventricular septal defect (VSD). We found a CHD frequency of 19% in a series of 32 patients identified either through a genetic or autopsy database. The cardiac lesions were much more varied and complex than previously reported and included asplenia syndrome, ventricular inversion associated with double outlet right ventricle, pulmonary atresia with VSD, double outlet right ventricle, and infradiaphragmatic total anomalous pulmonary venous connection. Pulmonary and renal abnormalities were more common in OAVS patients with CHD than in those where the heart was normal. PMID- 8357016 TI - Causal study of isolated ulnar-fibular deficiency in Hungary, 1975-1984. AB - A population-based and validated data set of 114 cases with isolated ulnar fibular deficiency was evaluated in Hungary, 1975-1984. Ulnar-fibular type had the third most common birth prevalence (0.07 per 1000) among isolated congenital limb deficiency types. This type is relatively rarely associated with nonlimb defects, a single limb is affected in two-thirds of cases, nearly all other cases had femur-fibula-ulna (FFU) dysostosis. Upper and lower limbs, right and left sides, are equally affected, however, there is an obvious male excess (71%). Case control analysis indicated a lower birth weight due to intrauterine growth retardation, higher birth order, lower socioeconomic status of parents, and a more frequent reported subfertility. The family study identified one familial cluster (one siboccurrence) among 331 first-degree relatives. PMID- 8357017 TI - Confirmation of trisomy 22 in two cases using chromosome painting: comparison with t(11;22). AB - We present a nonmosaic case of trisomy 22 in a liveborn, abnormal infant and a second case of a fetus who died in utero. Both have been verified cytogenetically and confirmed by in situ hybridisation with a centromeric alphoid probe and chromosome painting. The accuracy of the combined cytogenetic and molecular cytogenetic approaches in the karyotype determination is highlighted by comparison with a case showing partial translocation of chromosome 22 in t(11;22) (q23;q11). PMID- 8357018 TI - Absence of chromosome fragility at 19q13.3 in patients with myotonic dystrophy. AB - Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by a trinucleotide (AGC) amplification at 19q13.3. The degree of trinucleotide amplification may increase in successive generations and generally correlates with severity of the disorder. Because amplification of a trinucleotide repeat is also associated with the observation of a fra(X)(q27.3) in the fragile X syndrome, we investigated whether chromosome fragility at 19q13.3 might be inducible in patients with DM. Using 3 different culture stress systems (medium 199, RPMI 1640 with excess TdR, and RPMI 1640 with FudR) and high resolution chromosome analyses, we studied 6 individuals with DM and 5 unaffected relatives representing two unrelated families. Molecular studies were done on two of the most affected patients and showed AGC repeat sequences of 970 and 1,260 at 19q13.3. The normal range of AGC repeat is 5 to 30. We found no indication of fragility at 19q13.3 in any of these individuals. PMID- 8357019 TI - Newly recognized autosomal dominant disorder with craniosynostosis. AB - We report a family with a newly recognized form of autosomal dominant craniosynostosis. The disorder has high penetrance and variable expression with respect to sutural involvement and cranial abnormalities, ranging from fronto orbital recession to clover-leaf skull deformity. Associated problems included headache, poor vision, and seizures; intelligence, however, is normal. Assignment of a well-described syndromic designation, e.g., Crouzon, Pfeiffer, Saethre Chotzen, or Jackson-Weiss, is precluded based upon the absence of characteristic changes, i.e., midfacial hypoplasia, orbital hypertelorism, blepharoptosis, hand anomalies, or foot anomalies. The large size of this family and high penetrance of the disorder suggests that this may be an excellent candidate for positional cloning of a locus important in craniofacial development. PMID- 8357020 TI - Assessment of subcutaneous fat using ultrasonography in the Ullrich-Turner syndrome. AB - Subcutaneous fat was measured using an ultrasonic method (SF-US) in girls with Ullrich-Turner syndrome (UTS) and in height and weight-matched controls. The method is not influenced by changes in cutaneous compressibility, which is frequently abnormal in UTS especially at a younger age. SF-US in the arms was significantly less in UTS patients (ulnar SF-US: P < 0.05; triceps SF-US: P < 0.005) than in the control girls. Results in suprailiac SF-US measurement was also similar (P < 0.05). Though the mean SF-US in the subscapular region was less in UTS patients than the control girls, there was no statistically significant difference. It is demonstrated that subcutaneous fat in UTS patients is less in their arms than in girls without UTS and that trunkal fatness is not increased but rather decreased in the UTS. The ratio of lean body mass to weight seems higher in UTS patients than in girls with similar weight and height. PMID- 8357021 TI - Kohlschutter-Tonz syndrome: epilepsy, dementia, and amelogenesis imperfecta. AB - Kohlschutter-Tonz syndrome is a central nervous system (CNS) degenerative disease with convulsions and mental regression in which the affected children present with yellow teeth due to defective enamel. We present a family in which 2 affected children (a boy and a girl) were born to consanguineous parents. This report confirms the autosomal recessive inheritance of the disorder. The combination of a CNS and an enamel defect may represent pleiotropy or a contiguous gene syndrome. PMID- 8357022 TI - E. coli sepsis as a presenting sign in neonatal propionic acidemia. PMID- 8357023 TI - Discrepancy in mosaic findings between chorionic villi and amniocytes: a diagnostic dilemma involving 45,X, 46,XY, and 47,XYY cell lines. AB - Discrepancies between cytogenetic findings in chorionic villi (CV) and fetal tissue have been reported. Several embryogenic models have been proposed to explain such discrepancies. We describe a case in which analysis of the direct preparation showed 24% 45,X and 76% 46,XY, with 43% 45,X and 57% 46,XY cells in cultured villi. Amniocentesis results disclosed 97% 46,XY and 3% 47,XYY. No 45,X cells were found in cultured amniocytes. These findings suggest that nondisjunction occurred early in postzygotic cleavage resulting in 3 cell lines. It is postulated that through selection, the less viable 45,X cells died out among those destined to become fetus proper but persisted among the cytotrophoblast and extraembryonic mesoderm cells. While there is probably selection against all aneuploid cell lines, 47,XYY cells are more likely to survive in the fetus. An explanation for the lack of 47,XYY cells in the CV might be simply that the tissue sampled was not representative of the cytogenetic make up of the entire placenta. PMID- 8357024 TI - Monitoring for new multiple congenital anomalies in the search for human teratogens. AB - The ability of birth defects monitoring to detect new human teratogenic and mutagenic agents may be limited if only isolated defects are monitored. Surveillance for "new" multiple congenital anomalies (MCA) may improve the detection of environmental agents associated with new defect patterns. To evaluate the feasibility of such monitoring, we examined data from two programs: 1) the Metropolitan Atlanta Congenital Defects Program (MACDP), which ascertains infants with serious defects diagnosed in the first year of life, and, 2) the Italian Multicenter Register for Congenital Malformations (IPIMC), which ascertains newborn infants with birth defects from many hospitals in Italy. We focused on 24 relatively serious defects and defect groups. For a baseline period (MACDP: 1968-1988, 581,000 births; IPIMC: 1986-1989, 448,000 births), we identified all possible combinations of defects occurring in the same baby. For a test period (MACDP: 1989-1990, 77,000 births; IPIMC: 1990, 91,500 births), we identified babies with "new" MCA (i.e., combinations of defects not observed before in the system). During this period in MACDP, of the 85 babies with two or more defects, 9 babies had new MCAs. In IPIMC, of the 54 babies with two or more defects, 10 babies had new MCAs. A review of the records of infants with new MCAs in MACDP and IPIMC did not identify commonalities in maternal characteristics. This analysis illustrates the feasibility of monitoring for new MCAs in surveillance systems. This approach, complemented by an evaluation of exposures, may be a powerful additional tool in searching for human teratogens and mutagens. PMID- 8357025 TI - Steinfeld syndrome: report of a second family and further delineation of a rare autosomal dominant disorder. AB - We report on a fetus with alobar holoprosencephaly, microphthalmia, midline cleft lip and palate, absent nose, dysplastic ears, radial defects, pentalogy of Fallot, unilateral renal aplasia, absent gallbladder, vertebral anomalies, and absence of ribs. The father had a cleft palate, bilateral colobomas of the iris and retina, a bifid uvula, vertebral anomalies, and unilateral congenital hearing loss. His sister had a cleft lip. On the basis of this family and the family reported by Steinfeld [1982], this malformation syndrome can be defined as a rare autosomal dominant syndrome whose main component manifestations are holoprosencephaly, predominantly radial limb deficiency, heart defects, kidney malformations, absence of gallbladder, and vertebral anomalies. PMID- 8357026 TI - Caroline Crachami, the Sicilian fairy: a further note. PMID- 8357027 TI - Exclusion of the neurofibromatosis 1 locus in a family with inherited cafe-au lait spots. AB - We have performed linkage analysis in a small family with autosomal dominant inheritance of multiple cafe-au-lait spots (CLS) in order to clarify its relationship to classical von Recklinghausen disease (NF 1). We found that an affected woman had transmitted a different haplotype for markers flanking the NF1 gene to both of her affected daughters. These results exclude an allelic mutation of the NF 1 gene on chromosome 17 as the cause for inherited cafe-au-lait spots in this family. PMID- 8357028 TI - Cytomegalic type of congenital adrenal hypoplasia due to autosomal recessive inheritance. PMID- 8357029 TI - Another case of spondylocostal dysplasia and severe anomalies. PMID- 8357030 TI - Position statement on interphase in situ hybridization prenatal diagnosis. Report of the Southeastern Regional Genetics Group (SERGG). PMID- 8357031 TI - Presymptomatic DNA-testing for Huntington disease: pretest attitudes and expectations of applicants and their partners in the Dutch program. AB - We studied the baseline attitudes, prior to testing, of 70 applicants at risk for Huntington disease (HD) and their partners in the Dutch presymptomatic DNA testing program. Two thirds of the applicants were female; 36% already had children. The main reason (60%) for undertaking the test was for family planning. Other reasons were either to reduce uncertainty (43%) or to obtain certainty (38%). Partners of applicants stated that planning for the future was for them the most important reason (76%). Significantly more at-risk females (42%) than males (16%) anticipated an unfavorable test outcome. Quite remarkably, most applicants and partners denied that a positive result might have adverse effects on either personal mood, quality of life, or marriage. Only a few did not expect that a favorable result would induce relief. The eventual outcome of the test was expected to enable applicants to gain control over their future, whatever the results. Hence, we propose that the applicants form a self-selected group, based on their expectation that they will not be emotionally affected by either result. PMID- 8357032 TI - Legal and ethical issues in psychiatric genetic research. AB - Genetic research may uncover the causes of severe mental disorders, and many projects have been undertaken to locate the genes responsible for schizophrenia, bipolar disorder, and Alzheimer disease. A number of sensitive legal and ethical issues have been raised, including 1) protection of confidential data concerning research subjects; 2) the assessment of types and degree of risk to subjects who participate in such studies; 3) the legal and ethical acceptability of substituted judgement on behalf of patients who may not be competent to provide informed consent; and 4) the separation of research and clinical roles in areas such as genetic counseling. Federal regulations and other guidelines are of limited value in dealing with such concerns, and many important human subjects issues will need to be dealt with by the investigator, subject to approval by a local Institutional Review Board. There does seem to be general agreement that informed consent must be obtained, potential risks of research need to be minimized, and confidentiality of sensitive data must be protected. PMID- 8357033 TI - Do genes influence exposure to trauma? A twin study of combat. AB - Data from 4,029 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975) were used to examine genetic and non-genetic factors that influence wartime exposure to traumatic events. Specific events examined were volunteering for service in Vietnam, actual service in Southeast Asia, a composite index of 18 combat experiences, and information from military records about being awarded combat decorations. Correlations within monozygotic (MZ) and dizygotic (DZ) twin pairs for volunteering for service in Vietnam were 0.40 and 0.22, respectively. For actually serving in Southeast Asia, the MZ correlation was 0.41 and the DZ correlation was 0.24. Analysis of twin pairs in which both siblings served in Southeast Asia (n = 820) demonstrated a correlation for self-reported combat experiences within MZ and DZ pairs of 0.53 and 0.30, respectively. Heritability estimates ranged from 35 to 47%. The family environment did not have a significant effect on any of the variables. Analyses of data from military records regarding being awarded a combat decoration provided very similar results to those found for self-reported combat experiences. PMID- 8357034 TI - Novel association approach for determining the genetic predisposition to schizophrenia: case-control resource and testing of a candidate gene. AB - We have developed a two-tiered approach to elucidating the genetic predisposition to schizophrenia. The approach first involves the examination of candidate genes in a subset of schizophrenic individuals to identify DNA sequence variations of likely functional significance, i.e., that produce either structural alterations in the protein or affect the level of gene expression. Once identified, the prevalence of the aberrant allele is examined in a large group of unrelated schizophrenic cases and controls to assess whether a true disease association exists. Herein, we describe the establishment of a DNA bank on nearly 200 unrelated schizophrenic cases defined by DSM-III-R criteria and on over 300 unrelated, ethnically similar controls. Characteristics of the study sample are described. The study approach then is illustrated by testing known mutations in the phenylalanine hydroxylase gene, responsible for the autosomal recessive disease of phenylketonuria, in the case-control sample to determine if carriership of a mutant allele is associated with an increased risk of schizophrenia. Using PCR amplification of specific alleles (PASA), we screened 190 schizophrenic cases and 336 controls for two common point mutations in the phenylalanine hydroxylase gene. Two carriers were found among the controls, while none of the cases was shown to carry a mutant allele. Thus, carriership of either of two common mutations in the phenylalanine hydroxylase gene does not appear to be associated with an increased risk of schizophrenia. As additional candidate genes are tested in this case-control resource, adjustment for multiple comparisons will become crucial in order to reduce the chance of false positive findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357035 TI - Schizophrenia: genetics and the maternal immune response to viral infection. AB - Thirty years ago, Eliot Slater suggested that the reason schizophrenia was not progressively eliminated from the population was that the responsible gene also conveyed a compensatory advantage in terms of increased resistance to infection. If this selective advantage lies in the antibody response to certain viral infections, this could explain recent studies suggesting that exposure to influenza in the second trimester of gestation increases the risk of later schizophrenia. We propose that prenatal exposure to influenza induces maternal antibodies which then cross-react with proteins in the developing foetal brain, becoming foetal autoantibodies. Thus an immunogenetic response by the mother results in aberrant foetal neurodevelopment, the biological substrate for a proportion of adult schizophrenia. Initial research strategies to test this hypothesis are proposed. PMID- 8357036 TI - Usefulness of twin studies for exploring the etiology of childhood and adolescent psychiatric disorders. AB - It is estimated that approximately 12% of the individuals under the age of 18 in the United States have a diagnosable mental illness [Institute of Medicine, 1989]; however, only a minority of the etiological research in psychopathology focuses on disorders with childhood onset. The present report demonstrates the usefulness of twin studies in exploring the etiology of childhood and adolescent psychiatric psychopathology and reviews the design, methodology, and results from traditional twin studies of various behavioral disorders. Alternative twin designs are also reviewed in an effort to address the future direction of twin studies in the area of childhood and adolescent psychopathology and to illustrate that twin data have much more to offer the field of psychopathology than merely an initial test to rule in or to rule out a significant genetic contribution to the development of such behaviors. PMID- 8357037 TI - Agenesis of the corpus callosum with mental retardation and osseous lesions. AB - We report on a patient with agenesis of corpus callosum, mental retardation, and unusual hitherto undescribed bone changes. The latter include multiple Wormian bones, thin ribs, short, straight, laterally tapering clavicles, small iliac bodies, high iliac angles, triangular areas of sclerosis in the iliac bones, minimal metaphyseal irregularity, striated trabecular pattern in some metaphyses, granular ossification pattern of the patellae, hypoplastic distal phalanges, minimal flatness of phalangeal epiphyses, and retarded bone age. This patient represents a new mental retardation syndrome with agenesis of corpus callosum and unusual bone changes. PMID- 8357038 TI - DSM-III-R personality disorders in parents of schizophrenic patients. AB - This study examines the frequency of DSM-III-R personality disorders in parents of 58 patients who were admitted consecutively to a New York State psychiatric hospital with a first admission for a schizophrenia-like psychosis. For comparison, a control group of 65 families were randomly recruited who were in the same age group and denied any psychiatric history in their immediate families. Significantly more parents of the patients had a diagnosed personality disorder than controls. These were classified as schizoid, schizotypal, histrionic, and sadistic types by DSM-III-R criteria. While paranoid personality disorder was frequent, it was equally distributed among both groups of parents. These data suggest that the genetic boundaries to a "schizophrenia spectrum" disorder may extend further than previously thought and particularly the specific characteristics that are common to a wide variety of these disorders need to be examined in further analyses. PMID- 8357039 TI - Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores. AB - Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses. PMID- 8357041 TI - Bacterial Vaginosis. Conference proceedings. Seattle, Washington, August 8, 1990. PMID- 8357040 TI - History and review of bacterial vaginosis. AB - OBJECTIVES: Review publications that significantly impacted on the knowledge of bacterial vaginosis. STUDY DESIGN: Assessment of information on the epidemiology, bacteriology, and pathology of bacterial vaginosis. RESULTS: Bacterial vaginosis has a complex microbiology. Further information is required on the epidemiology. The large increase in the concentration of vaginal bacteria among patients with bacterial vaginosis is associated with postpartum and postsurgical infections and with preterm delivery. CONCLUSIONS: Bacterial vaginosis is the most important vaginal infection because of its potential to cause upper genital tract infection in specific settings. PMID- 8357042 TI - Epidemiology of bacterial vaginosis. AB - Studies of the prevalence of and risk factors for bacterial vaginosis are flawed by imprecision in diagnosis, failure to study large and well-characterized populations, selection bias, and failure to correct for confounding variables. Prevalences range from 5% for women without any symptoms to 25% for those with gynecologic symptoms. Although bacterial vaginosis is associated with nonwhite race and intrauterine contraceptive device use, these may represent surrogate markers for other presently unappreciated risk factors. PMID- 8357043 TI - The microbiology of bacterial vaginosis. AB - A group of microorganisms are present concurrently in high concentrations in the vaginas of women with bacterial vaginosis. The major members of the group are Gardnerella vaginalis, anaerobic gram-negative rods belonging to the genera Prevotella, Porphyromonas and Bacteroides, Peptostreptococcus species, Mycoplasma hominis, Ureaplasma urealyticum, and often Mobiluncus species. Facultative species of Lactobacillus are present in lower concentrations and are less prevalent in bacterial vaginosis than in women with a normal vaginal examination. The exact microbe(s) responsible for bacterial vaginosis is unknown whether among the organisms listed above or an unknown agent. The high concentrations of anaerobic gram-negative rods, peptostreptococci, and other opportunistic pathogens in the lower genital tract place women with bacterial vaginosis at increased risk for genital infections and adverse pregnancy outcomes. PMID- 8357044 TI - Diagnostic microbiology of bacterial vaginosis. AB - Bacterial vaginosis is characterized microbiologically by replacement of the Lactobacillus-predominant vaginal flora by Gardnerella vaginalis, Bacteroides species, Mobiluncus species, and genital mycoplasmas. A standardized, laboratory based diagnostic test for bacterial vaginosis is desirable in those instances in which a microscope is unavailable in the clinic or when the evaluator of the wet mount examination is inexperienced at recognizing clue cells. Vaginal cultures have excellent sensitivity for the diagnosis of bacterial vaginosis, but because the predictive value of a positive G. vaginalis culture is less than 50%, cultures are not recommended. Vaginal Gram smears are objective and reproducible, have 62% to 100% sensitivity, and have a positive predictive value of 76% to 100%. Diagnosis of bacterial vaginosis with use of Papanicolaou-stained smears has been reported, but standardized criteria have not been widely adopted. A rapid, office-based oligonucleotide probe test for high concentrations of G. vaginalis has been developed and may be useful when direct microscopy is unavailable or confidence in microscopic examination is low. Laboratory tests that detect microbial products unique to the vaginal fluid of women with bacterial vaginosis include detection of amines (putrescine, cadaverine, and trimethylamine), measurement of the relative levels of succinate and lactate in the vaginal fluid by gas chromatography, detection of proline aminopeptidase by colorimetric assay, or detection of sialidases in the vaginal fluid. Although these tests are not yet applicable to routine use, these research tests could be adapted for wider use in office laboratories. Vaginal Gram stains are more useful than culture for laboratory confirmation of bacterial vaginosis. PMID- 8357045 TI - Chorioamnionitis and bacterial vaginosis. AB - An improved understanding of bacterial vaginosis and of clinical intraamniotic infection and histologic chorioamnionitis has produced data showing strong associations among these conditions. It has recently been shown that the microorganisms in both bacterial vaginosis and clinical intraamniotic infection are similar, of which anaerobes, Gardnerella vaginalis, and Mycoplasma hominis are the predominant organisms in both. Furthermore, in the amniotic fluid of women with intraamniotic infection, strong associations among anaerobes, G. vaginalis, and M. hominis have recently been observed. In two epidemiologic studies (one in a high-risk group of women in labor and another in a lower risk group of antepartum women), the presence of bacterial vaginosis has been associated with the development of intraamniotic infection. Additional recent studies have provided new evidence that histologic inflammation of the placental membranes is associated with both clinical intraamniotic infection and positive cultures of the placenta. Multiple logistic regression analysis has shown a relationship between isolation of organisms from the chorioamnion and bacterial vaginosis. PMID- 8357046 TI - Premature rupture of membranes and bacterial vaginosis. AB - OBJECTIVE: Critically review obstetric, epidemiologic, microbiologic, and pathophysiologic information regarding the possible casual associations of bacterial vaginosis with premature rupture of membranes. METHODS: Observational and experimental studies are reviewed and correlated with in vitro and clinical, microbiologic, and pathophysiologic experiments in an effort to define possibly casual relationships with bacterial vaginosis and premature rupture of membranes and its maternal and perinatal sequelae. RESULTS: Considerable information shows that bacterial vaginosis, a common vaginal microbe-associated condition of reproductive age women, can be strongly (risk ratios up to 7.3, confidence interval 95%, 1.8 to 29.4) associated with preterm premature rupture of membranes as well as preterm labor and birth. Microorganisms of bacterial vaginosis produce factors including proteases (IgAse, collagenase, etc.) that can facilitate transport of bacteria to fetal membranes and impair fetal membrane integrity in experimental models. CONCLUSIONS: Controlled investigations are required to evaluate if treatment of bacterial vaginosis is associated with reduction of premature rupture of membranes and preterm birth. PMID- 8357047 TI - Bacterial vaginosis and postoperative infections. AB - Postoperative infections are common complications of obstetric and gynecologic surgery. The pathophysiology of both postcesarean endometritis and postoperative cuff cellulitis involves the ascending spread of potentially pathogenic microorganisms found in the vagina. Bacterial vaginosis is associated with increased vaginal concentrations of certain anaerobic and facultative bacteria. Bacterial vaginosis appears to be a risk factor for the development of postoperative infections in obstetrics and gynecology. PMID- 8357048 TI - Vaginal flora and pelvic inflammatory disease. AB - Forty-one patients with acute pelvic inflammatory disease were evaluated for the coexistence of bacterial vaginosis. Because all patients had a copious purulent vaginal discharge, microscopic criteria could not be used and microbiologic criteria were employed. The vaginal bacterial flora were not consistent with that of bacterial vaginosis, because Lactobacillus and other gram-positive bacteria dominated with colony counts of 10(3) to 10(5) cfu/ml (colony-forming units per milliliter). Endocervical specimens yielded Neisseria gonorrhoeae from 20 patients and Chlamydia trachomatis from 11 patients. Anaerobes were not dominant in any site sampled. A total of 147 bacteria were isolated from the endometrium, 16 (11%) of which were anaerobes. Thus the endogenous bacterial flora were not consistent with that of the microbiologic definition of bacterial vaginosis. N. gonorrhoeae was the most common isolate from the endocervix and endometrium; it was isolated three times more frequently from the endocervix and two times more frequently from the endometrium than was C. trachomatis. PMID- 8357049 TI - Historical review of the treatment of bacterial vaginosis. AB - The review of the treatment of bacterial vaginosis parallels the history of this syndrome. Before the syndrome was defined, treatment was local and nonspecific. Gardner and Dukes defined nonspecific vaginitis in 1955 as an infection caused by Haemophilus vaginalis. Therapy was directed toward this aerobic "pathogen" and included oral tetracycline and a triple sulfa vaginal cream. Subsequent studies indicated success with this regimen as well as with ampicillin, a drug with good aerobic activity. Since 1977, studies have shown the importance of anaerobes in this clinical syndrome. Both metronidazole and clindamycin have been found to have clinical success. The clinical definition of the disease makes evaluation of treatment difficult, because it includes women without symptoms. PMID- 8357050 TI - New approaches for the treatment of bacterial vaginosis. AB - OBJECTIVE: Review alternative approaches to oral metronidazole for the treatment of bacterial vaginosis. STUDY DESIGN: Assessment of clinical trials on the treatment of bacterial vaginosis with regimens other than 5 to 7 days of metronidazole. RESULTS: Single-dose metronidazole, 2 gm orally, is as effective as 5- to 7-day courses of oral metronidazole, with cure rates in the 80% to 90% range. Oral clindamycin results in more than a 90% clinical cure rate. Intravaginal clindamycin cream 2% and intravaginal metronidazole gel 0.75% are associated with clinical cure rates similar to those for oral metronidazole. CONCLUSIONS: Single-dose metronidazole, oral clindamycin, intravaginal clindamycin cream, and intravaginal metronidazole gel are effective and safe alternatives to a 5- to 7-day course of oral metronidazole for the treatment of bacterial vaginosis. PMID- 8357051 TI - Effect of the vitreous on the prognosis of full-thickness idiopathic macular hole. AB - We studied 112 eyes with full-thickness idiopathic macular holes (mean follow-up period, 5.7 years) to ascertain the effect of the vitreous on prognosis. Eyes were divided as follows: group 1, 58 eyes with no posterior vitreous detachment; group 2, 25 eyes with no posterior vitreous detachment initially and development of complete posterior vitreous detachment during follow-up; and group 3, 29 eyes with complete posterior vitreous detachment. In group 1, the macular hole enlarged in 37 eyes (64%), and the surrounding retinal detachment enlarged in 29 (50%); visual acuity decreased in 20 eyes (34%) by two or more Snellen lines. These percentages were significantly higher than in group 3 (14%, 10%, and 10%; P = .01, P = .01, and P = .03, respectively). Eyes with a full-thickness macular hole with no posterior vitreous detachment may have a greater risk of enlargement of the macular hole and surrounding retinal detachment, and thus a worse prognosis than eyes with posterior vitreous detachment. PMID- 8357053 TI - Association of herpes zoster ophthalmicus with acquired immunodeficiency syndrome and acute retinal necrosis. AB - We conducted a review to investigate the prevalence of human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS), in patients with herpes zoster ophthalmicus, as well as the incidence of acute retinal necrosis after herpes zoster ophthalmicus. All charts of patients seen at our institution between 1987 and 1992 with a primary diagnosis of herpes zoster ophthalmicus were reviewed. Of 112 patients with herpes zoster ophthalmicus, 29 (26%) had HIV or AIDS. All these patients were younger than 50 years at the time of diagnosis. Five of 29 (17%) immunocompromised patients had acute retinal necrosis after herpes zoster ophthalmicus. No acute retinal necrosis was identified in the nonimmunocompromised patients after herpes zoster ophthalmicus. We recommend that all patients younger than 50 years who have herpes zoster ophthalmicus at initial examination be tested for HIV. Additionally, HIV-infected patients should be monitored closely after herpes zoster ophthalmicus for development of acute retinal necrosis. Long-term oral prophylactic as well as initial high-dose intravenous acyclovir may be appropriate in HIV-infected individuals with herpes zoster. PMID- 8357052 TI - Risk factors for branch retinal vein occlusion. The Eye Disease Case-control Study Group. AB - The objective of our clinic-based case-control study was to identify risk factors for branch retinal vein occlusion. Between 1986 and 1990 data were obtained at five clinical centers from 270 patients with branch retinal vein occlusion and 1,142 controls. Data were collected from interviews, clinical examinations, and laboratory analyses of blood specimens. An increased risk of branch retinal vein occlusion was found in persons with a history of systemic hypertension, a history of cardiovascular disease, an increased body mass index at 20 years of age, a history of glaucoma, and higher serum levels of alpha 2-globulin. Risk of branch retinal vein occlusion decreased with higher levels of alcohol consumption and high-density lipoprotein cholesterol. The data suggest a cardiovascular risk profile for patients with branch retinal vein occlusion and indicate that 50% of patients with branch retinal vein occlusion may be attributable to hypertension. Our findings support current public health recommendations to diagnose and treat hypertension, reduce weight, increase physical activity, and maximize serum high density lipoprotein levels. PMID- 8357054 TI - Giant retinal pigment epithelial tears in acute retinal necrosis. AB - We observed large peripheral tears of the retinal pigment epithelium in two patients, a 59-year-old man and a 15-year-old girl, who had acute retinal necrosis. These tears ranged from 90 to 180 degrees of the circumference of the peripheral retinal pigment epithelium and occurred in areas of previous retinal viral infection. Both patients had curled folds of tissue at the posterior edge of the retinal pigment epithelial tear. During vitrectomy at the time of fluid air exchange, we noted the edge of these tears to sag posteriorly. Because of the area that was denuded of retinal pigment epithelium by the tears, we selected a more posterior location for argon laser endophotocoagulation in both patients. These large retinal pigment epithelial tears did not appear to have an adverse effect on the outcome of surgical treatment of the retinal detachments. PMID- 8357055 TI - A double-masked comparison of betaxolol and dipivefrin for the treatment of increased intraocular pressure. AB - Noncardioselective beta-adrenoceptor antagonists are used for treatment of increased intraocular pressure. Because these agents may be absorbed systemically, their use is of concern in patients with restricted pulmonary function. We compared the efficacy of betaxolol, a cardioselective beta adrenoceptor antagonist, and dipivefrin, an alpha/beta-adrenergic agonist. Seventy-six patients with open-angle glaucoma or ocular hypertension were randomly assigned to receive either betaxolol 0.5% or dipivefrin 0.1%. Patients were examined at two weeks, one month, two months, and three months. Intraocular pressure reductions were similar, with a mean decrease of 4.1 mm Hg in the betaxolol group and 3.5 mm Hg in the dipivefrin group. Both treatments caused similar minor increases in heart rate, typical with alpha-adrenergic agonists but atypical with beta-blockers. Stinging or burning in the betaxolol group was significantly (P = .008) greater than in the dipivefrin group. Our findings suggest that betaxolol and dipivefrin therapy are effective, equivalent ocular hypotensive agents. PMID- 8357056 TI - Ocular hypotony after trabeculectomy with mitomycin C. AB - Because mitomycin C reduces the resistance to aqueous outflow normally provided by postoperative subconjunctival fibrosis, we would expect to see more frequent hypotony after trabeculectomy with mitomycin C than after standard trabeculectomy. To evaluate the incidence of hypotony in trabeculectomy with intraoperative mitomycin C use, we performed a retrospective analysis on 52 eyes of 48 patients who underwent trabeculectomy with mitomycin C. Mitomycin C concentration was 0.4 mg/ml in all eyes, and treatment time ranged from 3 1/2 to seven minutes. We defined hypotony as intraocular pressure lower than 5 mm Hg on two examinations at least four weeks apart and six weeks or more postoperatively. Overall, average intraocular pressure was 22.7 +/- 10.7 mm Hg preoperatively and 10.4 +/- 5.0 mm Hg postoperatively (P < .001), a mean reduction in intraocular pressure of 12.3 +/- 11.5 mm Hg (47.0%). Hypotony occurred in 17 of 52 eyes (32.7%). Seven eyes required trabeculectomy revision for hypotony. Hypotonous eyes received longer treatment with mitomycin C intraoperatively, with a mean application time of 5.3 +/- 1.0 minutes for hypotonous eyes and 4.7 +/- 0.8 minutes for nonhypotonous eyes (P = .03). Sixteen of 43 eyes (37.2%) undergoing primary filtration became hypotonous, as compared to one of nine (11.1%) eyes that had previous filtering procedures (chi 2 = 2.30, P = .13). Nine of 17 hypotonous eyes (52.7%) and five of 35 nonhypotonous eyes (14.3%) had loss of two or more lines of Snellen visual acuity. Hypotony occurred in nearly one third of eyes treated with mitomycin C during trabeculectomy in our study. There was a statistically significant (P = .03) association of hypotony with longer application time of mitomycin C, and a trend toward increased incidence of hypotony in primary filtration. PMID- 8357057 TI - Treatment and prognosis of secondary glaucoma in Fuchs' heterochromic iridocyclitis. AB - After reviewing the records of 111 patients with Fuchs' heterochromic iridocyclitis, we studied the therapy and prognosis of secondary glaucoma in 30 of these 111 patients (27%) who had glaucoma or could be considered glaucoma suspects. Maximal medical therapy was unsuccessful in 22 of the 30 patients (73%). Surgical intervention (mostly trabeculectomies, half with 5-fluorouracil) successfully controlled intraocular pressure (< or = 21 mm Hg with or without medication) in 13 of the 18 operated-on patients (72%) after a mean follow-up of 26 months. All successfully operated-on patients retained a visual acuity of 20/80 or better. We had favorable results, possibly because of modern surgical techniques (use of 5-fluorouracil, sodium hyaluronate) or earlier surgical intervention, or both. PMID- 8357058 TI - An ultrasound biomicroscopic analysis of angle-closure glaucoma secondary to ciliochoroidal effusion in IgA nephropathy. AB - Immunoglobulin A nephropathy is a common glomerulonephritis of unknown cause. Episcleritis, scleritis, anterior uveitis, and keratoconjunctivitis sicca have been associated with this disease. We diagnosed angle-closure glaucoma secondary to ciliochoroidal effusion in a patient with IgA nephropathy confirmed by biopsy. High-frequency ultrasound biomicroscopy was used to determine internal relationships of angle structures and to follow changes with treatment. Supraciliary effusion undetected by B-scan ultrasound and retinal examination was easily imaged by ultrasound biomicroscopy. Glaucoma mechanisms included forward rotation of the ciliary processes, which caused direct angle closure in a manner similar to plateau iris. Ultrasound biomicroscopy showed that cycloplegia improved this mechanism by retracting the ciliary processes, but angle closure secondary to forward iris bowing from pupil block remained. Iridectomy was performed and immediately opened the angle. Ultrasound biomicroscopy proved a useful method of defining mechanisms and a helpful guide to treatment in this type of glaucoma. PMID- 8357059 TI - Postoperative endophthalmitis resulting from prosthesis contamination in a monocular patient. AB - Monocular patients who wear an ocular prosthesis may harbor pathogenic conjunctival flora both in the socket and in the contralateral eye. They may therefore be at increased risk of developing endophthalmitis after intraocular procedures. We studied a monocular, prosthesis-wearing, 86-year-old man who underwent cataract extraction, subtotal transpupillary vitrectomy, and intraocular lens insertion. Fulminant endophthalmitis ensued postoperatively, and despite complete vitrectomy and administration of intraocular antibiotics, the eye lost light perception. Intravitreal as well as conjunctival cultures bilaterally grew Proteus mirabilis. The patient disclosed that he cleaned the prosthesis frequently because of discharge. We considered an association between this bacterial colonization and the risk of developing postoperative endophthalmitis and suggest prophylactic measures for treatment of monocular patients undergoing intraocular procedures. PMID- 8357061 TI - Anophthalmic socket pain. AB - We examined and treated four patients with anophthalmic socket pain. Conditions responsible for this problem in this series included scleritis after evisceration, amputation neuroma, pain from a skull-base meningioma, and chemical dependency with drug-seeking behavior. The pain associated with the scleritis after evisceration responded to removal of the scleral remnant. The pain associated with the amputation neuroma responded to removal of the orbital implant and its pseudocapsule in which the amputation neuroma was embedded. The pain associated with the meningioma was intractable. The pain associated with the chemical dependency remained a persistent problem. A careful history and physical examination are critical in the evaluation of anophthalmic socket pain. Computed tomography or magnetic resonance imaging may be helpful in some cases. PMID- 8357060 TI - Corneal iron lines associated with the intrastromal corneal ring. AB - Corneal epithelial iron lines commonly occur, and their shape is characteristically influenced by the underlying corneal surface topography. We studied a pattern of iron deposition, observed after implantation of the Intrastromal Corneal Ring (KeraVision, Inc., Santa Clara, California). In five of ten patients undergoing placement of the Intrastromal Corneal Ring, an arcuate pattern of epithelial iron deposition was observed eight to 12 months postoperatively. There was no significant clinical or topographic difference over time among the corneas of patients who developed an iron line vs those who did not. Of the five patients with an arcuate epithelial iron line, three underwent explantation of their Intrastromal Corneal Ring at 12 months according to the study protocol. Iron deposition either reverted to a Hudson-Stahli pattern or disappeared in each of these three patients. PMID- 8357062 TI - The effect of optical defocus on the pattern electroretinogram in normal subjects and patients with Alzheimer's disease. AB - The pattern electroretinogram, thought to originate from the spatially sensitive inner retinal layers, was recorded in 16 patients with Alzheimer's disease and 16 age- and gender-matched control subjects under the following two test conditions: (1) optical defocus or inattention, without laser pointer, and (2) optical focus or attention, with laser pointer. By correcting for optical defocus with the laser pointer, control subjects increased their pattern electroretinogram amplitudes by 8% from a mean value of 2.65 microV (standard deviation, 1.12) to 2.87 microV (standard deviation, 0.93), whereas patients with Alzheimer's disease had a 19% increase in pattern electroretinogram amplitude from 2.20 microV (standard deviation, 0.86) to 2.62 microV (standard deviation, 0.64). By controlling for optical defocus, the coefficient of variation (standard deviation/mean) was reduced by 10% (from 42% to 32%) in normal subjects and by 14% (from 39% to 25%) in patients with Alzheimer's disease. A two-way analysis of variance (ANOVA) did not show a significant difference in amplitudes between populations, which indicates that the pattern electroretinogram may not be valuable in establishing an early diagnosis of Alzheimer's disease. In a second study conducted in 20 young, healthy normal subjects, plus lenses were used to defocus the checkerboard stimuli, before recording the pattern electroretinogram. We found that the pattern electroretinogram was extremely sensitive to optical defocusing such that the response amplitude decreased by 13% at 20/25 visual acuity and 19% at 20/30. Reduction of pattern electroretinogram amplitude caused by change in visual acuity is an independent source of artifact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357063 TI - Laser weapons designed to produce blindness. PMID- 8357064 TI - Retinopathy associated with low-dose tamoxifen. PMID- 8357065 TI - The prevalence of retinitis pigmentosa and congenital stationary night blindness in Israel. PMID- 8357066 TI - Symptomatic intraocular reflections from oval intraocular lens implants. PMID- 8357067 TI - Intracorneal hemorrhage with acute glaucoma. PMID- 8357068 TI - Application of mitomycin C during filtering surgery. PMID- 8357069 TI - Substitution of acetohexamide for acetazolamide. PMID- 8357070 TI - Microsporidal keratoconjunctivitis. PMID- 8357071 TI - Tarantula hair ophthalmia nodosa. PMID- 8357073 TI - Spontaneous orbital hemorrhage in a child with autoimmune hepatitis. PMID- 8357072 TI - Rosai-Dorfman disease involving four eyelids. PMID- 8357074 TI - Peripunctal eyelid oncocytoma. PMID- 8357075 TI - Paresis of the abducens nerve after trivial head injury. PMID- 8357076 TI - New challenges for tropical medicine. PMID- 8357077 TI - Three simple devices for preventing development of Aedes aegypti larvae in water jars. AB - We developed three types of covers that are easily fabricated from plastic screen locally manufactured in Thailand. The covers were designed to permit normal use of water jars for drinking, utility water uses, and water storage. Tests of the covers in the laboratory and field demonstrated that they could completely prevent successful development of Aedes aegypti (L.) in water jars. Initial experience in a village setting demonstrated that these devices were readily manufactured and used in a community-based program. Village residents adapted the covers to local patterns of water use, collecting rainwater through the screen and adjusting cover use to water depth. PMID- 8357078 TI - Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. AB - Volunteers immunized with gamma-irradiated Plasmodium falciparum sporozoites serve as the gold standard for protective immunity against mosquito-borne malaria transmission and provide a relevant model for studying protective immune effector mechanisms. During a 7-12 month period, we immunized four volunteers via the bites of irradiated, infected mosquitoes. Following these exposures to attenuated sporozoites, all four volunteers developed antibodies to sporozoites as measured by an immunofluorescence assay and by an enzyme-linked immunosorbent assay using the circumsporozoite (CS) protein repeat-based molecule R32LR as capture antigen. Three volunteers also developed antibodies against the nonrepeating (flanking) regions of the CS protein; the level of these antibodies paralleled the serum activity to inhibit sporozoite invasion of hepatoma cells in vitro. These three volunteers were protected against malaria transmitted by the bites of five infected mosquitoes. Two of these protected volunteers received additional immunizing doses of irradiated sporozoites and were subsequently protected against challenge with a heterologous P. falciparum clone. No detectable fluctuations were observed in circulating levels of tumor necrosis factor, interferon-gamma, or interleukin-6 during the course of this study. Analysis of the humoral and cellular immune responses of these protected volunteers is expected to yield important clues to additional targets of immunity against the pre-erythrocytic stages of malaria parasites. PMID- 8357079 TI - Effects of ingested human anti-sporozoite sera on Plasmodium falciparum sporogony in Anopheles stephensi. AB - We investigated the effects of human anti-sporozoite antibodies on the sporogonic development of Plasmodium falciparum in Anopheles stephensi. Equal volumes of washed human erythrocytes and human sera from 1) volunteers with protective immunity induced by immunization with irradiated P. falciparum sporozoites, 2) the same volunteers before immunization, or 3) Kenyans exposed to natural sporozoite transmission, were fed to cohorts of P. falciparum-infected A. stephensi on either day 5, 8, or 11 after infection. A fourth group of infected mosquitoes from the same cohort were not refed. In two experiments, the effects of anti-sporozoite antibodies were evaluated by determining the infection rates and parasite densities for oocysts and salivary gland sporozoites. There was no evidence that anti-sporozoite antibodies had any effect on the development or intensity of P. falciparum infection in A. stephensi. However, accelerated oocyst maturation was associated with mosquitoes taking a second blood meal, independent of serum source. Salivary gland sporozoites from mosquitoes that fed on immune human sera contained bound human IgG, which was detectable by indirect immunofluorescence assay. The infectivity and transmission potential of human IgG coated sporozoites is unknown. PMID- 8357080 TI - Leishmania (Viannia) panamensis-specific IgE and IgA antibodies in relation to expression of human tegumentary leishmaniasis. AB - Leishmania (Viannia) panamensis-specific IgE and IgA antibodies were quantified in patients with parasitologically confirmed American tegumentary leishmaniasis using a radioallergosorbent test (RAST) and an enzyme-linked immunosorbent assay (ELISA), respectively. The RAST values, presented as the mean +/- SEM percentage of total isotope added, were significantly elevated in patients having disease evolution greater than 12 months (3.14 +/- 0.91), as compared with those with an evolution time of 12 or fewer months (1.66 +/- 0.15) (P = 0.017). A separate group of patients, those with eosinophils in the biopsy specimen of their lesion, also had elevated mean RAST values (2.55 +/- 0.58) when compared with patients who did not demonstrate these cells in their biopsy specimens (1.32 +/- 0.24) (P = 0.038). Leishmania-specific IgA levels, presented as the mean +/- SEM optical density, were significantly higher for patients with mucocutaneous disease (0.40 +/- 0.03) than for patients with cutaneous disease (0.28 +/- 0.023) (P = 0.0063). Inhibition testing with homologous and heterologous antigens confirmed the specificity of these assays, and were used to assess cross-reactivity among L. (Viannia) subspecies and other kineto-plastic hemoparasites. Results demonstrate that patients with more severe forms of American tegumentary leishmaniasis, defined either as increased duration of disease or invasion of the mucosa, have elevated levels of Leishmania-specific IgE and IgA antibodies, respectively. PMID- 8357081 TI - Serologic response to Helicobacter pylori among children and teenagers in northern Chile. AB - The serologic response to Helicobacter pylori was determined in 388 children and teenagers living in Iquique, Chile by using an IgG enzyme-linked immunosorbent assay. Serum antibody levels, as measured by optical density, correlated strongly with age. Increases in the mean antibody level were seen primarily after age five, with rates of seropositivity increasing to > or = 70% among teenagers. The reasons for this age-related pattern of acquisition of infection remain to be determined. PMID- 8357082 TI - Mechanism of increased dissemination of chikungunya virus in Aedes albopictus mosquitoes concurrently ingesting microfilariae of Dirofilaria immitis. AB - We investigated whether concurrent ingestion of chikungunya virus and microfilariae of Dirofilaria immitis increases viral dissemination and multiplication in a mosquito vector. The increased rate of dissemination of this virus in mosquitoes concurrently ingesting both agents was found when homogenates of bodies and those of legs only were examined. It was significantly higher than that of controls ingesting the virus alone through the end of the experiment on day 14 after infection. We next studied the mechanism by which the presence of microfilariae enabled the virus to enter into the hemocoel and to reach the salivary glands. We checked our results using histopathologic procedures and electron microscopy by identifying holes produced by the microfilariae that penetrated the midgut epithelial layer. When the midgut of mosquitoes was punctured with a thin needle immediately after the mosquitoes ingested viruses, higher infection rates were observed than in mosquitoes without such punctures. PMID- 8357083 TI - Differential serodiagnosis of alveolar and cystic hydatid disease in the People's Republic of China. AB - Western blot analysis was carried out using crude antigens of Echinococcus multilocularis and 33 serum samples from the People's Republic of China to differentiate patients with alveolar hydatid disease (AHD) with active lesions from those with inactive lesions, those with other parasitoses including cystic hydatid disease (CHD), and healthy persons. This analysis was based on the detection of antibody responses against two polypeptides, Em18 and Em16, which appeared to be species specific and good indices for the differentiation of AHD with active lesions from AHD with inactive lesions. Twenty-one of the 33 samples showed antibody responses against Em18 and/or Em16. Fifteen were antibody positive for both Em18 and Em16, five were antibody-positive for Em18 only, and one was antibody-positive for Em16 only. Of the subjects from which the 33 samples were obtained, 12 patients had AHD with active lesions, two had AHD, but their lesions were resolved by surgical resections, 14 had CHD with active lesions, and five were apparently healthy people. Western blot analysis confirmed all 14 cases of AHD, three of the 14 cases of CHD, and showed that one of the five apparently healthy individuals had a positive serologic response for AHD. This apparently healthy person with a positive serologic response for AHD by Western blot analysis was found to be positive for the disease on re-examination. Thus, Western blot analysis based on the antibody responses against Em18 and Em16, especially against Em18, was extremely reliable for the detection of AHD with active lesions, although it failed to differentiate two of the 14 patients with CHD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357084 TI - Evaluation of the polymerase chain reaction for diagnosis of Lassa virus infection. AB - We evaluated the polymerase chain reaction (PCR) and hybridization procedures for diagnosis of Lassa fever. Primers were derived from a region of the small RNA segment of Lassa virus coding for the glycoprotein. Serum samples stored for a 14 year period from patients in Sierra Leone, West Africa were examined retrospectively. Blinded samples were then tested prospectively. Eighty-eight virus isolation-negative control sera were negative by PCR and hybridization. In the retrospective study, virus was isolated from 51 of 98 specimens from patients with Lassa fever, and 33 of these were positive for Lassa virus RNA by PCR, and 42 by PCR and hybridization. Fifteen were positive by PCR and hybridization but isolation-negative, and nine were positive by isolation but PCR/hybridization negative. Thirty-two were negative by all methods (sensitivity by PCR/hybridization compared with virus isolation 0.82, specificity 0.68). In a prospective blinded study of 195 patient sera, 51 were positive by PCR and virus isolation, and 24 were PCR positive but virus isolation-negative (sensitivity 0.66, specificity 0.71). After hybridization, 66 virus isolation-positive sera were positive. The sensitivity was 0.86 and the specificity was 0.59, and the probability of false-positive results compared with virus isolation was 32%, (chi 2 = 21.9, by McNemar's test). Since some specimens may not have contained viable virus, we re-analyzed the data of individual patients using laboratory-confirmed case definitions for Lassa fever. All specimens from patients in whom Lassa fever was excluded by serologic tests were negative by PCR/hybridization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357085 TI - Brazilian spotted fever in Espirito Santo, Brazil: description of a focus of infection in a new endemic region. AB - Although Brazilian spotted fever is known to occur in several adjacent states, infection with spotted fever group (SFG) rickettsiae has not previously been documented in the Brazilian state of Espirito Santo. We report a cluster of two proven and four suspected cases of Brazilian spotted fever in a small valley near Colatina, Espirito Santo. Four patients died without confirmatory serologic or pathologic studies. The two surviving patients had serologic and/or pathologic evidence of infection with SFG rickettsiae. Results of a survey done in 1991 confirmed the presence of antibodies reactive with SFG rickettsiae in the serum of dogs living in this region. Two of 25 dogs had elevated microimmunofluorescent antibody titers (1:64 and 1:256). Both seropositive dogs were pets of the index cases and lived in the valley where all six human cases were presumed to have acquired their infections. These cases and the results of the canine serosurvey suggest that a focus of virulent disease exists in an area not previously known to be endemic for SFG rickettsiae. PMID- 8357086 TI - Amblyomma americanum: a potential vector of human ehrlichiosis. AB - Polymerase chain reaction primers specific for Ehrlichia chaffeensis were used to amplify DNA from extracts of pooled ticks. Amplification was performed on extracts from 140 pools (1,579 total ticks) consisting of three tick genera collected from five states. The characteristic 389-basepair product was observed after amplification of extracts from seven different pools of adult Amblyomma americanum (117 pools, 1,462 ticks), but not from pools of nymphs. No specific product was observed after amplification of 20 pools (105 ticks) of Dermacentor variabilis and three pools of Ixodes scapularis (12 ticks). Ehrlichia chaffeensis was present in A. americanum at a minimum frequency of > or = 0.48%, suggesting that A. americanum may be a vector of human ehrlichiosis. PMID- 8357087 TI - Low-level Plasmodium falciparum transmission and the incidence of severe malaria infections on the Kenyan coast. AB - The transmission of Plasmodium falciparum was studied in relation to the incidence of severe malaria infections at Sokoke and Kilifi town, Kilifi District, Kenya. Intensive mosquito sampling during a one-year period yielded Anopheles gambiae s.l., An. funestus, and An. coustani. Anopheles gambiae s.l. was the predominant vector, comprising 87.9% and 97.9% of the total anophelines collected in Sokoke and Kilifi town, respectively. The proportion of An. gambiae s.l. with P. falciparum sporozoite infections was 4.1% (20 of 491) in Sokoke and 2.2% (3 of 138) in Kilifi town; no infections were detected in An. funestus or in An. coustani. Entomologic inoculation rates indicated that residents were exposed to only 8.0 infective bites per year in Sokoke and 1.5 in Kilifi town. Transmission was detected during only six months in Sokoke and three months in Kilifi town despite low-level, year-round vector activity. The yearly incidence of severe P. falciparum infections in children, 1-4 years of age was 24.1 per 1,000 in Sokoke and 4.2 per 1,000 in Kilifi town. Monthly patterns of transmission corresponded closely with the incidence of severe infections. At these sites on the coast of Kenya, the spatial and temporal incidence of severe malaria infections is associated with low-level P. falciparum transmission by vector populations. PMID- 8357088 TI - Trypanosomes and microfilariae in feral owl and squirrel monkeys maintained in research colonies. AB - A group of 358 owl and squirrel monkeys imported from Colombia, Peru, and Bolivia for the U.S. Agency for International Development Malaria Vaccine Development Program was examined for trypanosomes and microfilariae. Trypanosoma rangeli, isolated by hemoculture from Aotus nancymai, Saimiri b. boliviensis, and S. b. peruviensis, accounted for 76.6% of all trypanosome infections. Trypanosoma cruzi was isolated from 25 of 194 S. b. boliviensis, including two mixed infections with T. rangeli. Identifications of trypanosomes were confirmed by blinded tests with a panel of five rRNA probes on a subsample of cultures identified morphologically. Although no trypanosomes were isolated from Aotus vociferans or A. lemurinus griseimembra, positive serologic responses to T. cruzi were observed by indirect immunofluorescence assay in all species of monkeys examined and ranged from 42.1% among S. b. peruviensis to 92.3% among A. vociferans. Among T. rangeli-infected monkeys, 43.7% were seronegative for T. cruzi. No microfilariae were found in S. b. boliviensis or A. l. griseimembra. Mansonella barbascalensis and Dipetalonema caudispina were observed in A. vociferans, M. panamensis in A. nancymai, and M. saimiri and D. caudispina in S. b. peruviensis. Such naturally occurring infections in imported animal models are potential sources of accidental transmission to animal handlers and uninfected laboratory animals and can introduce confounding variables into otherwise well-planned and well-executed studies. PMID- 8357089 TI - A comparative field study of the relative importance of Lutzomyia peruensis and Lutzomyia verrucarum as vectors of cutaneous leishmaniasis in the Peruvian Andes. AB - A two-year field study of Andean cutaneous leishmaniasis (uta) in the valley of Purisima, Ancash Department, Peru has provided quantitative epidemiologic and entomologic evidence for the predominant role of Lutzomyia peruensis in the transmission of Leishmania peruviana in this endemic area. The monthly incidence in the valley was greatest in the wet season (from December to May), when Lu. peruensis was particularly endophilic. A significant correlation was detected between intradomiciliary (but not extradomiciliary) Lu. peruensis abundance and the monthly incidence of uta in the valley following a one-month time lag. In contrast, no significant correlation was detected between any measure of Lu. verrucarum abundance and the incidence of uta. Lutzomyia peruensis and Lu. verrucarum comprise more than 98% of all the sand fly captures made in this valley. The increase in incidence of uta with altitude, which reached a peak rate between 2,250 and 2,750 meters above sea level, was associated with an increase in the relative abundance of Lu. peruensis as compared with Lu. verrucarum. Seasonal and altitudinal variation was also detected in the peak time of activity for both sand fly species, a phenomenon that could significantly influence the transmission rate: later host-seeking sand flies being more likely to find sleeping, nondefensive, human hosts. PMID- 8357090 TI - Environmental sources of Cryptosporidium in an urban slum in northeastern Brazil. AB - Cryptosporidium is an important cause of diarrheal disease in children worldwide. To elucidate the environmental sources of this parasite, we selected an urban slum in Fortaleza, Brazil, a community with a known high incidence of cryptosporidiosis, and examined both stool smears from household animals (n = 127) and filtrates from local water sources (n = 18) for Cryptosporidium oocysts. Because previous work in this community has demonstrated the seasonal nature of human infection with Cryptosporidium, collections were made separately for the dry and rainy seasons. Of the 64 stools collected during the dry season (September-December 1990), four (6.3%) were positive by acid-fast staining for Cryptosporidium. Of the 63 rainy season samples (March-May 1991), nine (14.3%) were positive. Overall, oocysts were detected in 13 (10.2%) of 127 animal stool samples. Freshwater samples were obtained from a variety of sources including open and closed wells, and running city water and then processed. Four of 18 samples (22.2%), including a sample from city water were positive by at least one of two staining techniques (acid-fast and immunofluorescence). In summary, animals may serve as a reservoir of Cryptosporidium, with potential for the contamination of immediate household water sources. These findings may help to explain the high incidence of cryptosporidiosis among infants in this impoverished community. PMID- 8357091 TI - Is anemia an accurate predictor of vitamin A status in Pakistani children? AB - Serum retinol and hemoglobin levels were determined in 532 children aged 6-60 months living in urban slums of Karachi, Pakistan. Overall 67% (358 of 532) of children had hemoglobin levels of less than 11 g/dl, the World Health Organization definition of anemia for this age group. Estimations for red blood cell indices (hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red blood cell count) were done on a sample of 391 children to classify anemia morphologically. A similar percentage (69.8% [273 of 391 children]) of anemia was found in this group. The anemia was predominantly microcytic and hypochromic. Normocytic normochromic anemia was present in only 16.5%. Serum retinol levels were significantly correlated with hemoglobin (P < 0.002), hematocrit (P < 0.01), and red blood cell (P < 0.001) levels. However, anemia was found to be a poor predictor (positive predictive value [PPV] = 2.5%) for the presence of vitamin A deficiency (retinol < 10 micrograms/dl). The PPV increased to 54% if 20 micrograms/dl, which is an indicator of marginal vitamin A status, was used as the cutoff point. The sensitivity of the hemoglobin test was found to be 75% in correctly identifying vitamin A deficiency when retinol levels of 10 micrograms/dl and 20 micrograms/dl were both used as the cutoff points for deficiency. The specificity for the hemoglobin test varied from 33% to 40% when levels of 10 micrograms/dl and 20 micrograms/dl were used as the cutoff points for vitamin A deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357092 TI - Clinical and angiographic determinants of initial percutaneous transluminal coronary angioplasty success. AB - Clinical and anatomic determinants of primary success of percutaneous transluminal coronary angioplasty were retrospectively evaluated in 299 patients. Successful angioplasty (residual stenosis < 50%) was achieved in 350 (94%) of 373 lesions. The success rate in patients chronically treated with aspirin was higher than that of patients not treated with aspirin (95% versus 86%, P < 0.03). An additional finding was that the success rate in patients referred for coronary angioplasty because of acute myocardial infarction or postinfarction angina was lower than that of those without these characteristics (89% versus 96%, P < 0.01). No other clinical features studied influenced the outcome of coronary angioplasty. The angiographic characteristics of the lesions did not differ between patients with successful or failed angioplasty except for the degree of stenosis prior to the procedure, being lower in patients with successful procedure (92.4 +/- 7.6% versus 97.3 +/- 3.1%), P < 0.002). Thus coronary angioplasty can be performed with a high rate of success. Long-term pretreatment with aspirin may have a beneficial effect. PMID- 8357093 TI - The deltopectoral triangle as a landmark for percutaneous infraclavicular cannulation of the subclavian vein. AB - An anatomic landmark is identified and described that simplifies the technique of central venous cannulation via the subclavian vein. The commonly used techniques are an approach to the subclavian at the junction of the medial and middle thirds of the clavicle or at the midclavicular line. A described anatomic landmark, the deltopectoral triangle, is easily identified in virtually all patients and requires no measuring or extensive knowledge of anatomy for localization. Penetration of the skin at this landmark facilitates the procedure and produces less patient discomfort. Using this technique, the authors have successfully cannulated the subclavian vein in 92.7% (51/55) of attempts with a 5.5% (3/55) complication rate. The only complications were arterial punctures, which were treated with pressure and were of no consequence to the patient. PMID- 8357094 TI - Arterial mapping with color flow duplex imaging of the lower extremities after excimer-laser-assisted angioplasty. AB - The purpose of the present study was to evaluate the role of color flow duplex imaging (CFDI) in the follow-up of patients who have undergone excimer-laser assisted angioplasty of peripheral arteries. Sixty-one patients (40 men and 21 women) were studied (mean age +/- SD sixty-three +/- nine years). All patients were affected by peripheral vascular disease and, for this reason, underwent percutaneous excimer-laser-assisted angioplasty. Digital angiography and CFDI were performed before the laser procedure. CFDI was repeated at months 1, 3, 6, 9, and 12 after the laser procedure, whereas angiography was repeated after twelve months. Common, superficial, and profunda femoral arteries and popliteal arteries were visualized in looking for the presence of lesions and occlusions, and spectral analysis of Doppler signals was recorded. After the initial success, claudication was reported again by 9 patients, 7 of whom showed total occlusions. All reocclusions were discovered by CFDI and confirmed by angiography; 3 of these 7 patients underwent a second laser procedure. The remaining 2 symptomatic patients showed patent vessels and did not undergo angiography. Another 9 patients redeveloped an occlusion, unsuspected from clinical history and symptoms. All the reocclusions, confirmed by angiography, were diagnosed by CFDI. The data show that CFDI provides an accurate noninvasive technique for following up patients after excimer laser angioplasty, allowing for asymptomatic reocclusions to be recognized and treated if necessary, and permitting symptoms not due to reocclusions to be properly identified, thus avoiding unnecessary angiography. PMID- 8357096 TI - Circulating platelet aggregates indicative of in vivo platelet activation in pulmonary hypertension. AB - The authors investigated the existence of circulating cellular aggregates in 12 patients with moderate to severe pulmonary hypertension, using scanning electron microscopy. Peripheral venous blood was collected in the presence of 11.5 mM buffered ethylenediaminetetraacetic acid, in order to disperse freshly formed disaggregable aggregates. Irreversible aggregates represented by platelet clusters and/or platelet attachment to either leukocytes or red cells were identified in 7 patients with pulmonary hypertension. Endogenous platelet activation was further confirmed by a significant increase in plasma levels of beta-thromboglobulin in comparison with controls (33.8 +/- 14.1 vs 22.7 +/- 11.5 ng/mL respectively, p < 0.025). The presence of irreversible aggregates in the blood stream strongly suggests that cell-cell interactions actually occur in vivo in these patients. If so, therapeutic measures aimed at preventing in situ thrombosis and its consequences may be beneficial in this disorder. PMID- 8357095 TI - Prophylaxis of recurrent deep venous thrombosis. A randomized, prospective study using indobufen and graduated elastic compression stockings. AB - After an episode of deep venous thrombosis (DVT) 224 patients were randomized into four groups: a control group (A; 63 subjects); one receiving prophylaxis with indobufen (B; 60 patients)--an oral antiplatelet agent; one using graduated elastic compression stockings (C; 53); and one receiving prophylaxis with both indobufen and graduated stockings (D; 48). Patients were monitored over a three year period with color duplex scanning repeated every three months. In 46% of the controls there was at least one episode of recurrent DVT (RDVT). In patients receiving indobufen (group B) and using graduated compression stockings (group C) the incidence of RDVT was significantly lower (5% and 9.43%, respectively). The incidence of RDVT was further significantly reduced by the combination of the two methods (group D) (2.08%). In conclusion, RDVT is common and often asymptomatic and can be effectively prevented by prophylaxis with indobufen or graduated compression and more effectively by the combination of the two methods. PMID- 8357097 TI - Angina and coronary artery disease in patients with aortic valve disease. AB - The significance of angina pectoris in patients with aortic valve disease (AVD) and the need for coronary arteriography before valve replacement are controversial. The history of chest pain and coronary arteriographic findings were reviewed in 333 patients > or = forty years old, with AVD: 142 with aortic stenosis, 87 with mixed AVD and 104 with aortic regurgitation. The prevalence of coronary artery disease (CAD) was similar among different types of AVD. Angina pectoris was more frequent in patients with aortic stenosis (56%) and mixed AVD (53%) than in patients with aortic regurgitation (24%) (p < 0.0001). Similar results were found in patients with and without CAD. Twenty-six of 95 (27%) patients with CAD had no chest pain at all. The absence of any chest pain in CAD patients was more frequent in those > or = sixty years old than in those < sixty (p < 0.05). Thus, since a significant number of patients had CAD in the absence of any chest pain, the authors recommend coronary arteriography for all patients > or = forty years of age before aortic valve replacement. PMID- 8357098 TI - Abnormal erythrocyte rheology in patients with morbid obesity. AB - The objectives of this study were to investigate the rheological properties of the erythrocyte in patients with morbid obesity and to follow them up after a short-term weight loss. A fluorescent polarization method was used to assess erythrocyte membrane biorheology and to measure its fluidity. Eighteen subjects participated in the study: 8 healthy controls and 10 patients with morbid obesity. The erythrocyte membrane fluidity was obtained in the healthy subjects and in the patients with morbid obesity prior to and after a ten-day zero-calorie diet. Fluidity was determined by steady-state fluorescence polarization after incorporation of the lipophilic probe 1,6-diphenyl-1,3,5 hexatriene (DPH). With this method, the anisotropy parameter at 37 degrees C, which is inversely related to membrane fluidity, was obtained. The patients with morbid obesity revealed an abnormal erythrocyte rheology. The exhibited an abnormally low erythrocyte membrane fluidity as compared with normal subjects. The anisotropy parameter at 37 degrees C was 1.417 +/- 0.093 in these obese patients compared with 1.279 +/- 0.043 in normal-weight controls (p < 0.01). Upon a short-term significant weight loss from a body mass index (BMI) (weight/height2) of 39 +/- 5 to 36 +/- 5 kg/m2 (p < 0.05), the anisotropy parameter did not change (1.401 +/- 0.190). Thus, fluidity measurements permit recognition of an abnormal erythrocyte rheology in patients with morbid obesity. This abnormality may partially explain the excess cardiovascular and thromboembolic morbidity in morbid obesity. PMID- 8357099 TI - Increased plasma endothelin levels in Kawasaki disease: a possible marker for Kawasaki disease. AB - Plasma immunoreactive endothelin (iET) levels were investigated in patients with Kawasaki disease (KD). The iET level was 2.49 +/- 0.13 pg/mL in KD patients and 1.32 +/- 0.06 in age-matched control subjects, showing a significant increase with KD. The iET level was not increased in patients with febrile inflammatory diseases of bacterial origin without KD (non-KD group). Parameters indicating an inflammatory reaction, such as C-reactive protein, platelet count, white blood cell count, and interleukin-6 level, were increased in the KD patients. However, they were similarly increased in the patients with febrile diseases of bacterial origin and showed no significant differences between the two groups. This study is the first to report that plasma iET levels are elevated in a disease mainly involving vasculitis. These results suggest that blood iET levels are increased in KD patients as a result of the associated vascular endothelial damage and that iET can be a useful marker for the diagnosis of KD. PMID- 8357100 TI - Fatal bile pulmonary embolism following percutaneous transhepatic cholangiodrainage: case report and literature review. AB - Bile pulmonary emboli were present at autopsy in a seventy-year-old woman who had undergone percutaneous transhepatic cholangiodrainage for pancreatic carcinoma obstructing the common bile duct. The patient also developed hemobilia following the drainage. In spite of emergency surgery, she died on the third day after the operation. Microscopic findings of the lungs at autopsy disclosed numerous bile emboli in the smaller arteries, arterioles, and capillaries. Review of the literature showed 13 cases of bile pulmonary embolism, 10 of which had an obvious history of marked jaundice and trauma to the liver, like the present case. Bile enters the systemic circulation through a fistulous communication made by trauma between the biliary tree and the hepatic vein. PMID- 8357101 TI - Hyperparathyroidism associated with Raynaud's phenomenon--a case history. AB - The authors describe a patient with hyperparathyroidism and Raynaud's phenomenon. This association was hitherto undescribed. PMID- 8357102 TI - A variant of Noonan's syndrome: a case history. AB - The authors describe a variant of Noonan's syndrome hitherto undescribed. The special findings in this case were anomalous origin of the aortic arch vessels and focal glomerulonephritis. PMID- 8357103 TI - Invasive development of right atrial myxoma--a case report. AB - A thirty-nine-year-old man was admitted to the authors' department complaining of exertional dyspnea and high fever. An echocardiogram showed a mass in the right atrium, which was observed to move to the right atrium during the systolic phase and to the right ventricle during the diastolic phase. Magnetic resonance imaging showed that the mass developed from the right atrium to the superior vena cava. Intravenous digital subtraction angiography also showed a partial defect of the right atrium as well as obstructions of both the superior vena cava and the bilateral innominate veins. A pulmonary hemodynamic scintigram showed multiple defects at the mid and inferior areas of each lung, suggesting multiple pulmonary infarctions. The right atrial tumor was surgically removed. The superior vena cava and the innominate veins were found to be obstructed by organized thrombi, and the tumor had invasively grown into the right atrial wall. Histologic findings demonstrated that most of the tumor was composed of organized thrombi with scattered myxomatous tissue and was diagnosed as cardiac myxoma. These histologic findings suggest that the histogenesis of this right atrial myxoma might be thrombogenic. PMID- 8357104 TI - Association of congenital afibrinogenemia and K-dependent protein C deficiency--a case report. AB - The authors describe a rare case of congenital afibrinogenemia with concomitant K dependent protein C deficit that was brought to our observation for ischemic lesions of the foot in association with fibrinogen concentrate infusions. These lesions can be attributed to the association of various factors: fibrinogen infusion without heparin coverage, microtrauma, and protein C (PC) deficit. In fact, thromboembolic complications during afibrinogenemia were previously reported usually in association with substitutive therapy, and it is also known that PC deficit predisposes to thrombotic complications. The the authors' knowledge, the case described by them is the first in which PC deficit is associated with afibrinogenemia. This association cannot be explained by a common genetic mechanism because the genes for fibrinogen and for protein C are located on different chromosomes (chromosomes 4 and 2 respectively). PMID- 8357105 TI - Patent ductus arteriosus involving three generations--a case history. PMID- 8357106 TI - Relief of acute lower limb ischemia with percutaneous fenestration of intimal flap in a patient with type III aortic dissection--a case report. AB - Acute right lower limb ischemia developed in a patient with type III aortic dissection. Aortography revealed complete occlusion of the right common iliac artery by dissecting intima. Immediately percutaneous transfemoral fenestration with angioplasty balloon catheter was performed and marked improvement was obtained in clinical symptoms and angiographic findings. Unfortunately the patient died of rupture of the thoracic aorta about eleven hours after the procedure. The cause of death was not thought to be related to this procedure. The authors conclude that percutaneous fenestration should be considered as the treatment of choice for visceral or limb ischemia due to acute aortic dissection. PMID- 8357107 TI - The institutional review board as a mirror of scientific and ethical standards. AB - Decisions by institutional review boards (IRBs) are presumed to reflect the norms and standards of the scientific community. Such criteria have shifted as changes have occurred in experimental interventions and protocols, codes of federal regulatory agencies, norms among investigators, and expectations of participants. The tension created by shifting norms and standards raises two questions: (a) Should IRBs evaluate the scientific (e.g., design) features of the proposed research, and (b) should consistent standards be expected even in areas that are in constant flux (e.g., AIDS research)? We discuss these questions and propose a mechanism to keep IRBs abreast of emergent issues and sensitized not only to the costs of doing research but also to the costs of not doing it. PMID- 8357108 TI - The public's knowledge about psychologists and other mental health professionals. AB - A random sample of New London County, CT, residents received a questionnaire about nine mental health professions or professionals (MHPs): clergyperson, marriage and family counselor, nonpsychiatric physician, psychiatrist, psychiatric nurse, psychologist, psychotherapist, social worker, and telephone crisis counselor. Respondents defined each MHP and reported their satisfaction with treatment, which MHP they would recommend, their referral source(s), licensure requirements, and fees. A mixed-design analysis of variance was computed, with comfortableness as the dependent variable; age, sex, saw an MHP, and education, the between-subjects variables; and the nine MHPs, the within subjects variable. A significant MHP effect showed that physicians were perceived as slightly more comfortable than were psychologists (nonsignificant), who, nevertheless, were perceived as exceeding all other trained MHPs in the comfortableness experienced by their clients. PMID- 8357109 TI - Utility of nocturnal home oximetry for case finding in patients with suspected sleep apnea hypopnea syndrome. AB - OBJECTIVE: To evaluate prospectively the validity of home oximetry for case finding in patients clinically suspected of having the sleep apnea hypopnea syndrome (SAHS). DESIGN: Blinded comparison of home oximetry and polysomnographic nocturnal recordings. SETTING: Sleep clinic of a tertiary referral center. PATIENTS: A total of 240 outpatients referred because of reported sleep disturbances or daytime hypersomnia compatible with the diagnosis of SAHS. MEASUREMENTS: All participants had nocturnal home oximetry followed by a conventional polysomnographic study. The two recordings were interpreted blindly. Home oximetry test results were classified as abnormal (suspicion of sleep related breathing abnormalities) in the presence of repetitive, short-duration arterial oxyhemoglobin saturation. (SaO2) fluctuations without any absolute or relative decrease in the SaO2 threshold. The diagnosis of SAHS was confirmed when the apnea-plus-hypopnea index was greater than 10. RESULTS: Based on the results of the polysomnographic sleep study, 110 patients had SAHS (apnea-plus-hypopnea index, 38.1 +/- 2.5/h; mean +/- SE). Home oximetry test results were interpreted as abnormal in 176 patients (this included 108 patients with SAHS and 68 without SAHS) and were read as normal in 62 patients without SAHS and in 2 with SAHS. Home oximetry testing had a sensitivity of 108/110 or 98.2% (95% Cl, 93.6% to 99.8%); a specificity of 62/130 or 47.7% (Cl, 38.8% to 56.6%); a positive predictive value of 108/176 or 61.4%; and a negative predictive value of 62/64 or 96.9%. CONCLUSIONS: A negative home oximetry test result is helpful in ruling out the diagnosis of SAHS in patients clinically suspected of having this syndrome, because a negative test result reduced the probability from 54.1% to 3.1% in our patients. However, a positive oximetry test increased the probability from 46% to 61.4% in our group of patients. PMID- 8357110 TI - A reassessment of the importance of "low-count" bacteriuria in young women with acute urinary symptoms. AB - OBJECTIVE: To determine whether a statistical association exists between "low count" bacteriuria (> 10(2) to 10(4) colony-forming units/mL) and acute urinary symptoms in young women. DESIGN: Prospective, case-control study. SETTING: Gynecology clinic at a student health center. PATIENTS: Women with or without urinary or vaginal symptoms. MEASUREMENTS: History of urinary infections and sexual activity. Quantitative determination of bacteriuria and pyuria and bacterial species; urine leukocyte esterase test; specific gravity; creatinine levels; vaginal leukocytes; and in-vitro culture of urine. RESULTS: The frequency of recent sexual activity, pregnancies, and contraceptive practices was not statistically different between women with acute urinary symptoms and asymptomatic controls. Escherichia coli and Staphylococcus saprophyticus were the only microorganisms statistically associated with urinary symptoms and pyuria (P < 0.001). Low counts of these organisms were found in 10.2% of asymptomatic women. As the bacterial count increased, the association between these organisms and symptoms increased, and a step-wise increase occurred in the frequency and magnitude of pyuria, but the specific gravity and urine creatinine levels remained unchanged. Escherichia coli, even at low counts, grew well in the patients' own urine. Pyuria (> 20 leukocytes/mm3) was present in 19.6% of asymptomatic women and was associated with vaginal leukorrhea. CONCLUSIONS: "Low count" bacteriuria was statistically more frequent among young women with urinary symptoms than among asymptomatic controls. The low counts could not be explained by dilution of the urine or failure of the bacteria to grow well in the patients' urine. These findings suggest that the infection was not established in the bladder urine and that "low-count" bacteriuria might be an early phase of urinary tract infection. PMID- 8357111 TI - The prevalence of deep venous thrombosis in patients with suspected paradoxical embolism. AB - OBJECTIVE: To determine the prevalence of venous thrombosis in patients with suspected paradoxical embolism. DESIGN: Observational study. PATIENTS: Two hundred sixty-four patients with clinically suspected embolic events underwent contrast transesophageal echocardiographic evaluation. Forty-nine patients (24 women, 25 men) had a patent foramen ovale. Forty-one patients had acute stroke, and 8 had acute limb ischemia. SETTING: Echocardiography laboratory of a community hospital. MEASUREMENTS: The presence of a patent foramen ovale was assessed by transesophageal contrast echocardiography. Forty-two patients had venographic evaluation of the lower-extremity venous system. RESULTS: Venous thrombosis was clinically suspected in 6 patients and documented in 24 of the 42 patients with patent foramen ovale who underwent venographic study (57%; 95% Cl, 41% to 72%). Venous thrombosis was confined to calf or popliteal veins in 15 cases. Fifteen of 17 patients who had venographic evaluation within 7 days of the index event had thrombosis compared with 9 of 25 patients who had later evaluations (P = 0.001). More patients with venous thrombosis than without venous thrombosis had a history of previous thromboembolism (13 of 24 compared with 1 of 18 [corrected], respectively; P = 0.001). CONCLUSION: When a patent foramen ovale is detected in a patient with embolism, occult leg vein thrombosis is frequently present. PMID- 8357112 TI - A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. AB - OBJECTIVE: To prospectively develop and validate a predictive model for the occurrence of new delirium in hospitalized elderly medical patients based on characteristics present at admission. DESIGN: Two prospective cohort studies done in tandem. SETTING: University teaching hospital. PATIENTS: The development cohort included 107 hospitalized general medical patients 70 years or older who did not have dementia or delirium at admission. The validation cohort included 174 comparable patients. MEASUREMENTS: Patients were assessed daily for delirium using a standardized, validated instrument. The predictive model developed in the initial cohort was then validated in a separate cohort of patients. RESULTS: Delirium developed in 27 of 107 patients (25%) in the development cohort. Four independent baseline risk factors for delirium were identified using proportional hazards analysis: These included vision impairment (adjusted relative risk, 3.5; 95% Cl, 1.2 to 10.7); severe illness (relative risk, 3.5; Cl, 1.5 to 8.2); cognitive impairment (relative risk, 2.8; Cl, 1.2 to 6.7); and a high blood urea nitrogen/creatinine ratio (relative risk, 2.0; Cl, 0.9 to 4.6). A risk stratification system was developed by assigning 1 point for each risk factor present. Rates of delirium for low- (0 points), intermediate- (1 to 2 points), and high-risk (3 to 4 points) groups were 9%, 23%, and 83% (P < 0.0001), respectively. The corresponding rates in the validation cohort, in which 29 of 174 patients (17%) developed delirium, were 3%, 16%, and 32% (P < 0.002). The rates of death or nursing home placement, outcomes potentially related to delirium, were 9%, 16%, and 42% (P = 0.02) in the development cohort and 3%, 14%, and 26% (P = 0.007) in the validation cohort. CONCLUSIONS: Delirium among elderly hospitalized patients is common, and a simple predictive model based on four risk factors can be used at admission to identify elderly persons at the greatest risk. PMID- 8357113 TI - Clinical trial of clarithromycin for cutaneous (disseminated) infection due to Mycobacterium chelonae. AB - OBJECTIVE: To determine if clarithromycin monotherapy is safe and effective in treating cutaneous disease (especially disseminated disease) due to Mycobacterium chelonae (formerly M. chelonae subspecies chelonae). DESIGN: An open, noncomparative trial of clarithromycin as single-drug therapy. SETTING: Nationwide referrals. PATIENTS: Culture-positive patients whose M. chelonae came from a cutaneous source and whose isolate was submitted to a single referral laboratory for susceptibility testing. INTERVENTION: Clarithromycin, 500 mg twice a day by mouth for 6 months. No attempt was made to alter use of immunosuppressive drugs. MAIN OUTCOME MEASURES: Acid-fast bacilli smears and cultures of skin lesions during and after treatment, with monitoring of clinical response, side effects, and development of new lesions. RESULTS: Fourteen patients (10 with disseminated disease) were enrolled in the study and completed at least 3 months of therapy. Underlying diseases included rheumatoid arthritis, other autoimmune disorders, and organ transplantation. All were taking corticosteroids (93%) or cyclophosphamide (7%). All patients had an excellent response to therapy, with only mild side effects from the drug. Two patients died of other diseases after improving clinically but while still taking medication. One noncompliant patient who prematurely discontinued therapy after 3.5 months relapsed 1 month later with an isolate resistant to clarithromycin. The remaining 11 patients have all completed therapy given for a mean of 6.8 months (range, 4.5 to 9 months). Therapy has been discontinued for 9 of the 11 patients for at least 6 months (mean, 7.1 months; range, 6 to 12 months), with no evidence of relapse. No remaining patient had positive acid-fast bacilli smears or cultures of skin lesions after 1 month of therapy. CONCLUSIONS: Clarithromycin may be the drug of choice for cutaneous (disseminated) disease due to M. chelonae, although more patients with long-term clinical follow-up need to be studied. PMID- 8357114 TI - Echocardiographic manifestations in a patient with pseudoxanthoma elasticum. PMID- 8357115 TI - Rapid brain calcification after ischemic stroke. PMID- 8357116 TI - Levothyroxine therapy in patients with thyroid disease. AB - PURPOSE: To review the indications for and the proper monitoring of levothyroxine therapy in patients with thyroid disease. DATA SOURCES: Relevant English language articles published from 1966 to 1992 were identified through a MEDLINE search and manual searches of both identified articles and selected endocrinology texts. STUDY SELECTION: Studies, case reports, and review articles that contained data on the pathophysiologic aspects of relevant thyroid disorders and on the pharmacologic aspects of, indications for, and administration of levothyroxine therapy. DATA EXTRACTION: Data on the epidemiology, clinical manifestations, complications, and treatment of thyroid disorders were analyzed with respect to patient selection, methods, diagnostic criteria, and conclusions. These data were used to develop a rational approach to the management of such patients. RESULTS OF DATA SYNTHESIS: Levothyroxine is a reliable and commonly prescribed drug to treat thyroid disease, but excessive dosage may have adverse effects. In patients with hypothyroidism, levothyroxine is used as replacement therapy. For most patients, therapy can be initiated with a full replacement dosage (1.6 micrograms/kg body weight), which is usually 75 to 100 micrograms/day for women and 100 to 150 micrograms/d for men. The goal is to normalize the serum thyroid stimulating hormone concentration. Levothyroxine is also used to suppress the serum thyroid-stimulating hormone concentration. A trial of thyroid-stimulating hormone suppressive therapy is indicated for most patients with benign solitary nonfunctioning thyroid nodules and for those with a history of thyroid cancer. Levothyroxine in non-thyroid-stimulating hormone-suppressive doses may also be indicated for patients with nontoxic multinodular goiter and for certain patients after lobectomy for benign thyroid nodules. CONCLUSIONS: With proper patient monitoring, levothyroxine replacement therapy should be effective, inexpensive, and free of complications. Recommendations for thyroid-stimulating hormone suppression with levothyroxine are based on risk-benefit considerations of the biologic characteristics of the thyroid disorder and the individual patient. PMID- 8357117 TI - Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis. AB - PURPOSE: To examine the cost-effectiveness of empirical, parenteral antibiotic treatment of patients with chronic fatigue and myalgia and a positive serologic result for Lyme disease who lack classic manifestations. DATA SOURCES: Peer reviewed journals, opinion of experts in the field, and published epidemiologic reports. STUDY SELECTION: Consensus by authors on articles that indicated methods for patient selection; on criteria used for diagnosis; on immunologic methods used for classifying patients; on the dose and duration of therapy; and on criteria by which responses to therapy were ascertained. DATA EXTRACTION: In a cost-effectiveness model, the costs and benefits of empirical parenteral therapy for patients seropositive for Lyme disease were compared with a strategy in which only patients having classical symptoms of Lyme disease were treated. DATA SYNTHESIS: In areas endemic for Lyme disease, the incidence of false-positive serologic results in patients with nonspecific myalgia or fatigue exceeds by four to one the incidence of true-positive results in patients with nonclassical infections. Treatment of the former group of patients costs $86,221 for each true positive patient treated. The empirical strategy causes 29 cases of drug toxicity for every case in the more conservative strategy. If patients were willing to pay $3485 to eliminate anxiety about not treating possible true Lyme disease, the empirical strategy would break even. CONCLUSION: For most patients with a positive Lyme antibody titer whose only symptoms are nonspecific myalgia or fatigue the risks and costs of empirical parenteral antibiotic therapy exceed the benefits. Only when the value of patient anxiety about leaving a positive test untreated exceeds the cost of such therapy is the empirical treatment cost effective. PMID- 8357119 TI - Appropriateness of parenteral antibiotic treatment for patients with presumed Lyme disease. A joint statement of the American College of Rheumatology and the Council of the Infectious Diseases Society of America. PMID- 8357118 TI - Chronic active hepatitis: the challenge for a new nomenclature. AB - OBJECTIVES: To review the etiologic agents and pathogenic mechanisms of chronic active hepatitis, to describe the current nomenclature for this disease and highlight its shortcomings, and to propose guidelines for change. DATA SOURCES: Relevant references were identified through a MEDLINE search (1982 to 1992), through prominent review articles and texts, and through a personal library of journals and reprints. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: All pertinent articles on the etiologic agents, pathogenic mechanisms, and nomenclature of chronic active hepatitis were studied. DATA SYNTHESIS: Subtypes of chronic active hepatitis can be defined by etiologic agent or immunoserologic marker, and these subtypes may have different clinical features, prognoses, pathogenic mechanisms, and treatments. An unauthorized jargon has evolved to accommodate these subtypes, and it may wrongly or prematurely connote their validity. Patients with cryptogenic disease, mixed viral and immunologic features, and atypical findings lack a formal designation. No established mechanism exists for modification of the nomenclature. CONCLUSIONS: Chronic hepatitis can be subclassified into different subtypes that are defined by etiologic agent or by predominate pathogenic mechanism. A new nomenclature must be based on this knowledge. Formal mechanisms must be established to revise the nomenclature and to promulgate change. PMID- 8357120 TI - Brain death: reconciling definitions, criteria, and tests. AB - Brain death has been discussed extensively for the last 25 years. Most investigators now believe that requiring death of the entire brain as the criterion for brain death in the Uniform Determination of Death Act and the standard clinical tests of brain death outlined in the Report of the Medical Consultants to the President's Commission have produced a satisfactory resolution of the issues surrounding the determination of death. However, we show that satisfying the standard medical tests does not guarantee that all brain functions have actually ceased and that there is tension between the legal criterion and the standard clinical tests. After considering and rejecting six possible reconciliations, we present an alternative approach that does not acknowledge any sharp dichotomy between life and death and incorporates the proposition that the questions of when care can be unilaterally discontinued, when organs can be harvested, and when a patient is ready for the services of an undertaker should be answered independent of any single account of death. PMID- 8357121 TI - Predator and prey. PMID- 8357122 TI - A magnificent whole. PMID- 8357123 TI - Large-scale trials of thrombolytic therapy for acute myocardial infarction: GISSI 2, ISIS-3, and GUSTO-1. PMID- 8357124 TI - Rochalimaea infections. PMID- 8357125 TI - Aminophylline and cardiac arrest. PMID- 8357126 TI - Cost and effectiveness of hepatitis B immunization. PMID- 8357127 TI - The benefit of increasing sulfonylurea dose. PMID- 8357128 TI - The benefit of increasing sulfonylurea dose. PMID- 8357129 TI - Vital capacity as a predictor of premature death. PMID- 8357130 TI - The familial Muir-Torre syndrome. PMID- 8357131 TI - Differential collapsing pulses: a new clinical sign. PMID- 8357132 TI - Standardizing criteria for logistic regression models. PMID- 8357133 TI - The Mendoza Line and in-training examination scores. PMID- 8357134 TI - What is internal medicine? PMID- 8357135 TI - What is internal medicine? PMID- 8357136 TI - What is internal medicine? PMID- 8357138 TI - What is internal medicine? PMID- 8357137 TI - What is internal medicine? PMID- 8357139 TI - [Local anesthesia in hernia surgery]. AB - After a short historical outline, the advantages of, the indication for, and the contraindications for local anaesthesia in hernial surgery are considered. The principal pharmacological characteristics of the most widely-employed local anaesthetics are set out. Preoperative preparation of the patient, intraoperative monitoring and the technique of local anaesthesia employed by the authors are described in detail. PMID- 8357140 TI - Inguinal and femoral hernioplasty utilizing polypropylene patch and plug. PMID- 8357141 TI - The office hernioplasty and the Trabucco repair. PMID- 8357142 TI - The Shouldice operation. PMID- 8357143 TI - Femoral hernia. PMID- 8357144 TI - [Complicated extremely large hernias. The technical problems]. AB - The surgical repair of giant hernias is a serious problem. To return the viscera that are contained within the hernia sac, to the abdominal cavity, we can cause an increase of abdominal pressure, that influences the motion of the diaphragm. In fact, post-operative acute respiratory failure is always possible, in these patients. To have a good operation, the preoperative preparation by physiotherapy is very important, it helps the patient to utilize at most his pulmonary capacity. In the surgical repair of these cases, it is necessary to increase the volume of the abdominal cavity by some different techniques, in order that the intra-abdominal pressure does not increase too much. The reabsorbable prosthesis is placed in direct contact with viscera and fixed to the peritoneum and posterior rectus sheaths, so that it allows to increase the volume of the abdominal cavity. Dacron mesh is fixed to fascia and muscles and assures a long time contentitive function. To choose the right operation depends on every single case, so the techniques are different and they often can not be codified. In the text there are described three complicated cases and the surgical repair that has been used. The last case describes a personal techniques that uses two prosthesis to create a new peritoneal cavity and a new pre-peritoneal space. The results obtained let us say that the surgery which has a functional base and the alloplastic prostheses have permitted to operate some clinical cases very difficult. PMID- 8357145 TI - [The repair of inguinal hernias with a large Dacron-mesh prosthesis and the preperitoneal approach]. PMID- 8357146 TI - [The complications of hernia surgery]. PMID- 8357147 TI - [The effect of ionizing radiation on the onset of breast carcinoma]. AB - The authors examine the influence of ionogenic radiations on the onset of breast cancer. They remark the connection between the doses of radiations and the incidence of cancer and point out that the danger increases when the women is exposed to radiations during her fertile age. They present five cases of patients suffering from breast cancer where the exposition to radiations may have been a cause of the cancer. PMID- 8357148 TI - [The epidemiology of gallbladder cancer in Italy. ISTAT data 1970-1987]. AB - The Italian surgeon needs to know the real situation about gallbladder carcinoma in Italy, his professional field of action: real incidence, sex and age characteristics and regional distribution with useful correlations to define the risk population. We can use nowadays the ISTAT data (since 1969 also in magnetic tape) about such neoplasia, based on death denunces. These differentiate gallbladder carcinoma from others hepatobiliary neoplasms and are referred to the whole national territory and allow and analyze for the various regions a period of 18 years (from 1970 to 1987). We have therefore the facility of a statistical index which give us the possibility to compare directly the specific mortality taxes between very different regions of residence from the point of view of population density, sex and age distribution on each year of the period considered. Also in Italy incidence of gallbladder carcinoma shows an absolute and relative increasing with age in both sexes, reaching the peak in the seventy's, with a M/F rate between 1/3 to 1/2, and with global incidence that is increasing in the last years. Risk factors could be in the age older than 50 years, in the females, in the long standing gallbladder lithiasis with wide cholesterinic stones on the basis of a chronic inflammation and consequent dysplasia, in the diet more far from the mediterranean's, and finally in papillomas and papillomatosis of gallbladder. PMID- 8357149 TI - [The risk factors and prevention of recurrences in rectal surgery]. AB - The authors report their own experience of 34 patients operated on for rectal cancer. In 8 cases abdomino perineal resection and in 26 anterior resection with anastomoses (6 in second time) were performed. Operatory mortality was nil and with an average follow up of 34 months 5 local recurrences were observed 16%. Among the risk factors examined the most important seems to be the stage of the disease; imperative it is therefore a correct surgical approach which warranted a significant reduction of local recurrences. This surgical approach includes a safety distal clearance from the tumour (at least 2.5 cm.), radical lymphadenectomy and complete removal of the mesorectum. PMID- 8357150 TI - [The current state of adjuvant treatment in carcinoma of the resected colon]. AB - After radical surgery for colo-rectal cancer, the prevention of local recurrence and/or distant metastasis, represents the key factor of the active measures adopted by surgeons and oncologists. Recent trends of the research in this field, show that an effective chemotherapy is the goal to achieve. Our review of the literature on this subject, is aimed to make some remarks about the results of the main randomized protocols of adjuvant chemotherapy conducted in recent years, comparing the efficacy of different treatments. We should consider two ways of administering the chemotherapy: the systemic route, the classic one, and the portal route, especially designed to prevent liver metastasis. At the end of our review, we can conclude the following: poly-chemotherapy (MF or MOF) did not show real advantages compared to 5-FU alone the combination of 5-FU + Levamisole, showed an undoubtable efficacy in Dukes' C colorectal cancer the efficacy of intra-portal vein chemotherapy for Dukes' B colorectal cancer, has been proved in one report only, therefore we are waiting for a confirmative answer from the several similar investigations prompted recently. The analysis of such investigations may contribute, in future, to establish new protocols combining chemotherapy with immunotherapy and particularly, systemic chemotherapy with loco regional one. PMID- 8357151 TI - [Hemangioma of the masseter: a rare location of a pathology not always accurately diagnosed]. AB - The hemangiomas of the skeletal muscles are rare. The authors describe a case of masseter muscle hemangioma, dwelling upon the problems of differential diagnosis that are present for the straight rapport that the muscle contract with the parotid gland. Thus, the surgeon is led to confuse the malformation with a neoplasm of the parotid gland. PMID- 8357152 TI - [Laparoscopic cholecystectomy and percutaneous echo-guided cholecystostomy. Their applications in acute cholecystitis]. AB - Laparoscopic cholecystectomy is nowadays proposed as elective treatment in acute cholecystitis; the advantages obtained with this method are comparable with those of laparoscopic cholecystectomy outside inflammatory complications. Moreover in emergency we have the advantage of better diagnostic definition and less surgical trauma. When acute cholecystitis affects high risk patients from the anesthesiologic view percutaneous US-assisted cholecystostomy is considered more valuable than the medical conservative treatment. Drainage of gallbladder is followed from a dramatic clinical improvement with more time for a laparoscopic cholecystectomy or for a percutaneous lithotripsy or eventually for the simple withdrawal of the catheter. PMID- 8357153 TI - [The laparoscopic treatment of splenic rupture, a case report]. AB - The case report refers to a splenic traumatic rupture treated conservatively by diagnostic and interventional laparoscopy. The peculiarities of the method are discussed and related to the various problems of the situation: direct observation, washing and the use of fibrin glue are the key of the success. PMID- 8357154 TI - [A case of a left-sided gallbladder treated surgically via laparoscopy]. AB - The authors relate about a case of symptomatic cholelithiasis, in which the organ was located in the inferior face of III hepatic segment and the surgical treatment was performed by laparoscopy. They discuss about etiopathogenesis of this anomaly, symptomatology referred by the patients and diagnostic procedures. Finally, they stress the necessity, in this case, to perform the cholecystectomy by anterograde approach in order to well visualize the anatomic structures and be safe to avoid injury of hepatic pedicle. PMID- 8357155 TI - An immunogenic self-peptide for T cells in mice with experimental myasthenia. PMID- 8357156 TI - In situ production of interleukins in hyperplastic thymus from myasthenia gravis patients. PMID- 8357157 TI - Myf-4 does not mediate AChR receptor subunit mRNA expression in thymic tissues. AB - We investigated whether a MyoD gene family member plays a role in the expression of AChR or AChR-like proteins in human thymus. We amplified from thymic tissue, mRNA of subunits of the fetal- and adult-type AChR, and Myf-4, a gene product that appears to regulate AChR expression. RNA extracted from paraffin-embedded thymic tissue of five myasthenics and five nonmyasthenics was subjected to reverse transcription followed by polymerase chain reaction using primers specific for these mRNAs. Thymic RNA from eight of ten patients contained transcripts of the alpha- and epsilon-subunits (specific for the adult-type AChR). Presence of these transcripts did not correlate with thymic pathology or clinical presentation. No gamma-subunit (specific for the fetal-type AChR) or Myf 4 transcripts were found. Our results indicate that mRNA for the adult-type AChR is expressed in thymic tissue and is expressed by mechanisms not involving Myf-4. Thymic AChR subunits may be the primary epitope that initiates the immune response in MG against the adult-type AChR. PMID- 8357158 TI - Myasthenia gravis-associated thymic epithelial tumors express neurofilaments and are associated with antiaxonal autoimmunity. PMID- 8357159 TI - Thymus histology and acetylcholine receptor antibodies in generalized myasthenia gravis. PMID- 8357160 TI - Molecular evolution of the binding site of the acetylcholine receptor. PMID- 8357161 TI - Degradation of acetylcholine receptors at vertebrate neuromuscular junctions. PMID- 8357163 TI - Stereo view of conformation and myasthenogenicity in synthetic peptides of acetylcholine receptor alpha-subunit. PMID- 8357162 TI - cDNA and genomic clones encoding the human muscle acetylcholine receptor. PMID- 8357164 TI - Approaches for studying the pathogenic T cells in autoimmune patients. AB - Our provisional conclusions from this work are as follows. (1) For screening responses of established lines, native human AChR is not prohibitively scarce, especially if it is concentrated onto beads, and class II-transfected TE671 cells may be useful too; both may give vital evidence of AChR-specificity, but it is still crucial to confirm that with synthetic peptides. (2) For mapping epitopes, panels of full-length and shorter recombinant human polypeptides, and of synthetic peptides, are invaluable complementary material: longer peptides tend to stimulate particularly strongly. (3) Initial selection with pooled synthetic peptides can easily generate interesting lines from both patients and controls, but they may depend on the artificial processing sites that are an inevitable consequence of arbitrarily chosen start and stop points. Of course, these might conceivably be employed in unusual antigen-presenting cells (such as thymic myoid cells), so we cannot totally dismiss such "cryptic" epitopes. This system can sometimes select T cells responding to "natural" epitopes too, as now reported for tetanus toxin. Nevertheless, for these and other reasons, at present, we strongly favor using the longest human recombinant material possible, because it is apparently processed more naturally. This must be combined with rigorous screening for reactivity to E. coli-derived contaminants plus concomitant mapping of epitopes as above. Use of intact AChR for initiating lines may yet become feasible. (4) The T cells thus isolated and characterized so far are proving to be heterogeneous in the epitopes and presenting class II molecules they recognize, and in their T-cell receptor gene usage. It is premature to claim key myasthenogenic epitopes or clonotypes, but HLA-DR3 and the linked -DQw2 do not appear to monopolize presentation. (5) Assessing the disease-relevance of these T cells is a separate problem, highlighted by their apparent similarity in healthy controls. In the meantime, to test their potential pathogenicity, we are assaying their cytokine profiles and ability to help specific antibody production in vitro. In the hope that they do prove to be relevant, we are also using some of them to test possible therapeutic strategies that might prove applicable in the patients. PMID- 8357165 TI - Differences in acetylcholine receptor-antibody interactions between extraocular and extremity muscle fibers. AB - There are two types of motor nerve innervation patterns and AChR distributions in human EOM: single and multiple. The latter is further divided into two subgroups that are restricted to EOM and are not found in limb muscles. Epitopes that are unique to EOM end-plates exist. Some OMG patients have antibodies that are specifically targeted to those epitopes. These antibodies are functionally active and can cause AChR loss in EOM end-plates. In addition to AChRs, specific components constructing the microenvironment surrounding them may also be involved in the susceptibility of EOM in myasthenia gravis. PMID- 8357167 TI - Molecular structure of a monoclonal antiacetylcholine receptor antibody and of a corresponding monoclonal antiidiotopic antibody. PMID- 8357166 TI - Effector mechanisms of myasthenic antibodies. PMID- 8357169 TI - Abnormal immunoregulation involving the IL-2/IL-2 receptor complex in myasthenia gravis. PMID- 8357168 TI - Differential recognition by T cells of the P3A+ and P3A- isoforms of the human acetylcholine receptor alpha-subunit. PMID- 8357171 TI - Stimulation of specific T cells by human AChR adsorbed to immunomagnetic particles. PMID- 8357170 TI - VH gene family utilization of antiacetylcholine receptor antibodies in experimental autoimmune myasthenia gravis. PMID- 8357172 TI - Steps in the generation of autoantibodies. PMID- 8357173 TI - T-cell receptor expression in murine myasthenia gravis. PMID- 8357174 TI - EAMG induced in rabbits by immunization against peptides representing human AChR alpha 138-199. PMID- 8357175 TI - A novel therapy for myasthenia gravis by reducing the endocytosis of acetylcholine receptors. PMID- 8357176 TI - The hu-SCID myasthenic mouse. A new tool for the investigation of seronegative myasthenia gravis. PMID- 8357177 TI - Tolerance to AChR induced by AChR-coupled syngeneic cells: clonal anergy? PMID- 8357178 TI - Acetylcholine receptor-specific T cells are present in the normal immune repertoire. A study with recombinant polypeptides of the human acetylcholine receptor alpha-subunit. PMID- 8357179 TI - T-cell receptor gene usage of acetylcholine receptor-specific T-helper cells. PMID- 8357180 TI - Production of interferon gamma and interleukin-2 by peripheral blood lymphocytes of patients with myasthenia gravis and other autoimmune diseases. PMID- 8357181 TI - Cells from mice exposed chronically to D-penicillamine show proliferative responses to D-penicillamine-treated self (macrophage/dendritic cells): a graft versus-host response? PMID- 8357182 TI - Response of peripheral blood mononuclear cells from myasthenia gravis patients to exogenous interleukin-2. PMID- 8357183 TI - Acetylcholine receptor presentation by B cells using heterobifunctional antibody conjugates. PMID- 8357184 TI - T-cell receptor genes in autoimmunity. AB - T cells are primary participants in the pathogenesis of the MHC-dependent autoimmune diseases, and therefore, evidence for association of TCR V-gene repertoires with such disorders has been actively sought. With very few exceptions, no clear-cut evidence for correlation of particular RFLP-defined V-C region genomic polymorphisms with autoimmune disease predisposition has thus far been demonstrated. With regard to TCR V-gene repertoires engaged in responses to autoantigens, restricted use of certain V beta and V alpha genes in response to myelin basic protein has been documented in animal models. In many spontaneous and experimentally induced animal and human autoimmune diseases, however, the picture is far from clear. Although dominance of certain TCR V genes has been noted, the clonal restrictions are not absolute; they differ from one study to another and from one patient to another. Such variations may be caused by MHC allele-dependent determinant selection mechanisms, secondary T-cell infiltrates in inflammatory sites, different patient populations and stages of disease, or the involvement of different pathogens that, nevertheless, lead to the same clinical entity. Overall, the results indicate that efforts to intervene therapeutically in autoimmune diseases by vaccination with modified T-cell clones, V region-synthetic peptides, or TCR blocking analogues may not be easily applicable. Further studies on the characterization of the specific antigens involved in autoimmune disease pathogenesis is required in order to accurately address the issue of TCR utilization in autoimmune diseases. PMID- 8357185 TI - Regulation of experimental autoimmune myasthenia gravis by synthetic peptides of the acetylcholine receptor. PMID- 8357187 TI - Muscarinic receptor-mediated modulation of acetylcholine release in mice with passively transferred Lambert-Eaton myasthenic syndrome. PMID- 8357186 TI - Human muscle acetylcholine receptor reactive T and B lymphocytes in myasthenia gravis. PMID- 8357188 TI - The thymus in myasthenia gravis. PMID- 8357189 TI - Congenital myasthenic syndrome attributed to an abnormal interaction of acetylcholine with its receptor. PMID- 8357191 TI - The thymus and T-cell tolerance. PMID- 8357190 TI - Myasthenic syndromes attributed to mutations affecting the epsilon subunit of the acetylcholine receptor. PMID- 8357192 TI - Congenital end-plate acetylcholine receptor deficiency and short channel open time. PMID- 8357193 TI - Strategies for treatment of myasthenia gravis. PMID- 8357194 TI - A clinical therapeutic trial of cyclosporine in myasthenia gravis. AB - We randomly assigned 39 patients with steroid-dependent generalized myasthenia gravis to treatment with cyclosporine (5 mg/kg per body weight in divided doses) or placebo. Duration of treatment was 6 months. Patients were evaluated monthly. Primary measures of efficacy were quantified strength testing, antihuman acetylcholine receptor antibody titer, and dosage of corticosteroid medication. At the end of the study, patients in the cyclosporine group had significantly greater improvement in strength (p = 0.004) and a reduction in antireceptor antibody titer (p = 0.01). Percentage reduction of steroid medication was greater in the cyclosporine group, although the difference was not statistically significant (p = 0.12). There were no treatment failures, and there was one drug failure in the cyclosporine group. In the placebo group, there were three treatment failures. No significant nephrotoxicity was noted at this dosage during the first 6 months. During the subsequent 18 months of open-label therapy, continued reduction in steroid dosage occurred. Cumulative side effects, however, caused 35% of patients to discontinue the medication; 10% did so secondary to slowly progressive nephrotoxicity. PMID- 8357195 TI - Clinical improvement of myasthenia gravis by treatment with a chimeric anti-CD4 monoclonal antibody. PMID- 8357197 TI - Infections occurring in hospitalized myasthenia gravis patients. PMID- 8357196 TI - Searching for prognostic factors at the time of thymectomy for myasthenia gravis. Correlation between outcome after long-term follow-up and immunophenotype of thymic and peripheral blood lymphocytes. PMID- 8357198 TI - Therapies for exacerbation of myasthenia gravis. The mechanism of action of intravenous high-dose immunoglobulin G. PMID- 8357199 TI - Single-fiber EMG and repetitive stimulation of the same muscle in myasthenia gravis. PMID- 8357200 TI - Analysis of HLA DPB1 allele in patients with myasthenia gravis in Japan. PMID- 8357202 TI - How reliable are imaging procedures in detecting residual thymus after previous thymectomy? PMID- 8357201 TI - Myasthenia gravis is associated with two DQ alpha/beta heterodimers. PMID- 8357203 TI - An in vitro model for disease-specific immunotherapy in myasthenia gravis using soluble MHC class II bound to AChR-derived peptide. PMID- 8357205 TI - Electrophysiological characteristics in seronegative myasthenia gravis. PMID- 8357204 TI - HLA haplotype in myasthenia gravis (MG) of Japanese children. Correlative studies between MG patients and their normal siblings and parents. PMID- 8357206 TI - 3,4-Diaminopyridine in Lambert-Eaton myasthenic syndrome and myasthenia gravis. PMID- 8357207 TI - Relapses in patients with myasthenia gravis treated with azathioprine. PMID- 8357208 TI - Immunosuppressive treatments. Their efficacy on myasthenia gravis patients' outcome and on the natural course of the disease. PMID- 8357209 TI - Treatment strategies in myasthenia gravis. PMID- 8357210 TI - Transplantation of myasthenia gravis thymus to SCID mice. PMID- 8357211 TI - Molecular analysis of intrathymic nicotinic acetylcholine receptor. PMID- 8357212 TI - Nicotinic neuronal acetylcholine receptor alpha-3 subunit transcription in normal and myasthenic thymus. AB - Thymic transcription of the alpha-3 subunit of the AChR was studied through sequencing and PCR analysis of thymic cDNA clones, Northern blotting, and ribonuclease protection assays. This analysis revealed at least three, 3' end sequence variants for the alpha-3 subunit as well as a variant that results from the alternative splicing of an antisense 122 bp Alu sequence between exons 5 and 6 of the normal transcript. The spliced Alu sequence not only shifts the exon 6 reading frame but also carries an in-frame stop codon. If translated, this variant transcript would produce a truncated peptide lacking the fourth transmembrane domain of the subunit and carrying a carboxy terminus dodecapeptide not found in any other known AChR subunit sequence. The putative variant subunit may lack biological activity and should differ antigenically from its normal counterpart. In comparing the normal, the MG hypertrophic, and the MG thymoma for transcription of the alpha-3 subunit and its 122 bp variant, it was found that there were no qualitative or quantitative changes in alpha-3 transcript expression in the MG hypertrophic thymi. Thymomas, however, showed an overall decrease in alpha-3 transcription and a comparative increase in beta-amyloid precursor transcription. The decrease in the levels of alpha-3 transcription in thymomas may be related to the proliferation of thymic epithelial cells. PMID- 8357213 TI - High IL-6 gene expression and production by cultured human thymic epithelial cells from patients with myasthenia gravis. PMID- 8357214 TI - Microsurgical scalp and skull reconstruction using a serratus anterior myo osseous flap. AB - In reconstruction of large scalp and skull defects, the usefulness of microvascular free tissue transfer is manifest. We have performed 4 scalp and skull reconstructions by free serratus anterior osteomuscle flap transfer. The usefulness of serratus anterior osteomuscle flap for reconstruction of combined, extensive scalp and skull defects is emphasized. PMID- 8357215 TI - Platysma myocutaneous flap for intraoral and surface reconstruction. AB - Different procedures have been described for facial and oral reconstruction after malignant tumor removal, such as skin grafts and local and distal staged flaps. Myocutaneous island or free flaps are the method of choice for these reconstructions. Our experience concerns the use of the platysma myocutaneous flap in 12 patients after intraoral and extraoral malignant tumor resection. Six patients had squamous cell carcinomas, i.e., 2 malignant melanomas of the skin and 4 squamous cell carcinomas of the oral mucosa. The complete tumor resection was controlled by frozen-section biopsy in all patients, but for 7 of them a functional or radical neck dissection was performed. We suggest including in the flap the external jugular vein. The results were evaluated from an oncological, functional, and aesthetic point of view. We noticed 2 recurrences in a minimum follow-up of 4 years. The functional and aesthetic results were quite satisfactory and no serious complications were noticed in our series. However, the primary disadvantage of this interesting flap is that the dominant vasculature derived from the submental branch of the facial artery is seldom visualized. In spite of this, it should be regarded as very useful for limited intraoral or surface coverage problems in an arc extending 10 cm from the level of the facial artery at the mandible. This arc includes the cheek, the lower lip, the chin, the floor of the mouth, and the mastoid area. PMID- 8357216 TI - Experimental effects of intraorbital tissue expansion on orbitomaxillary growth in anophthalmos. AB - A skeletal growth study evaluating an intraorbital tissue expander as a globe replacement in anophthalmos was conducted in an infant animal model. Twenty-one 21-day-old kittens were equally divided into the following three groups: a control, a unilaterally enucleated, and an enucleated-expanded group. Postoperative three-dimensional computed tomographic scans were obtained at 5 months of age immediately before study termination. Linear orbital, orbitomaxillary, and zygomaticomaxillary dimensions were measured on the scans and compared at necropsy with orbital volume assessment on the dry skulls. Control animal orbits averaged 21.5 mm in height, 21.0 mm in width, and 5.1 cm3 in orbital volume, and an orbitomaxillary-zygomaticomaxillary height-to-width ratio of 31.0: 24.5. The control side, its contralateral side, and the contralateral orbits of the treated sides were not significantly different. By study completion, enucleation resulted in a significant loss of orbital volume (mean, 1.9 cm3; p < 0.001) confirmed by deficient orbitozygomaticomaxillary measurements. The expanded orbits showed no loss of volume (mean, 5.2 cm3; p > 0.1) and normalization of all linear midfacial structures. This study demonstrates that early expansion emanating from within the orbital soft tissue positively affects both the skeletal and lid anomalies associated with congenital globe loss or early enucleation. PMID- 8357217 TI - The perineal artery axial flap. AB - We have found the perineal artery axial flap to be useful in reconstruction of moderate defects of the perineum. The experimental surgical technique and clinical applications of the perineal artery axial flap are updated. Our experience with 10 patients over the past 5 years is reviewed. The advantages of this flap are that it is thin and the donor site morbidity is minimal. PMID- 8357218 TI - Diagnostic criteria of vascular lesions in the face. AB - Diagnostic criteria of vascular lesions in the face were studied in a series of 57 patients investigated and treated during the years 1980 to 1990. Twenty-eight had hemangiomas and malformations, and 29 had telangiectasia. At present, the histological diagnoses are most commonly used to describe vascular lesions, but unfortunately this gives little idea of the actual appearance of the lesion. In the present study, the clinical appearance was compared and correlated with the findings at the time of surgery, with the angiographs, and with the histological diagnosis. An attempt was undertaken to coordinate the accepted clinical, microscopic, and angiographic classifications with our own results. Based on the modern concepts of pathology of angiogenesis and the conclusions drawn from our present investigation, the "new," unifying classification of vascular lesions was compiled. This classification is presented in the form of a diagram. PMID- 8357219 TI - A new classification of vascularized flaps in plastic and reconstructive surgery. AB - Advances during the last 15 years in microsurgical technique and in our understanding of vascular anatomy have led to the development of two new branches of plastic and reconstructive surgery. The first is the transfer of free composite flaps with microvascular anastomoses. The second is transposition of island flaps solely on a proximal or distal vascular bundle. Both types of operations require an adequate vascular pedicle to provide sufficient blood circulation for flap viability and survival in the recipient site. PMID- 8357221 TI - Midfacial fracture repair in the adult rat. AB - The consensus in the literature is that fracture healing within the midface occurs via fibrous union. Clinical experience with the surgical correction of established traumatic deformities has not borne this out. An earlier histological examination with human biopsy specimens demonstrated that eventually repair occurred by direct bony union. However, a recent study in a rabbit model challenged this conclusion and indicated that the process of new formation resembles secondary bone formation as in endochondral formed bone. The purpose of our inquiry is to elucidate further the process of midfacial bony repair in an adult male Sprague-Dawley rat model. PMID- 8357220 TI - Identification of xanthine oxidase activity following reperfusion in human tissue. AB - In this series of experiments, we surveyed xanthine oxidase activity after microvascular transfer in the venous effluent after reperfusion of human rectus abdominis muscle (n = 8) and jejunum (n = 4). Enzyme activity was correlated with duration of ischemia and biochemical markers of cellular injury. Xanthine oxidase (XO) activity was measured spectrofluorometrically using a pterin assay, whereas cellular injury was measured with commercial creatinine phosphokinase activity assay and lipid peroxidation products using a spectrophotometer. The data demonstrated that XO activity was statistically significantly increased in muscle flaps kept at room temperature during ischemia compared with muscle flaps that were cooled (p < 0.05). Creatinine phosphokinase activity was also increased after 15 minutes of reperfusion in muscle flaps that were not cooled (p < 0.05). Two of the jejunal free flaps had ischemia times of > 1 hour and had elevated XO activity after reperfusion despite cooling (p < 0.05). Two other jejunal flaps had ischemia times of < 1 hour, but in one case, the XO activity was increased before harvest. The other case had no increase in XO activity. PMID- 8357222 TI - Ultrasound analysis of 150 patients with silicone gel breast implants. AB - One-hundred fifty patients with silicone gel breast implants were investigated using ultrasound (US) studies, to assess the integrity of their implants. US testing demonstrated 8 patients (5.33%) with implant rupture, which was subsequently confirmed at surgery. A further 4 patients were "false negatives," wherein they presented with normal US tests, but at subsequent surgery, demonstrated secondary alterations in their implant envelopes. Two of these patients demonstrated profound local silicone gel "bleed," whereas the 2 others had frank implant rupture. There was also one "false positive" patient. The total known prevalence of patient implant alteration was therefore 12, i.e., 10 with ruptures and 2 with profound local gel "bleed," in 150 patients (8.0%). Five of the 10 patients with ruptured implants had undergone multiple closed capsulotomies in the past. The mean time of diagnosis after implant insertion was 8.5 years (range, 2.0-18 yr). US analysis may provide a safe, simple, inexpensive, noninvasive tool to assist in the identification of ruptured silicone gel breast implants. There were significant limitations with technique, however, in that there were 4 false negatives, and 1 false positive result, and US analysis was not helpful in diagnosing profound silicone gel bleeds. PMID- 8357223 TI - Effects of magnetic resonance imaging fields on gold eyelid loads. AB - Magnetic resonance imaging is frequently used for visualization of soft tissues of the head and neck. It was the purpose of this study to determine whether gold eyelid weights, used for treatment of lagophthalmos in facial palsy, would be deflected at high magnetic strengths during imaging. Ex vivo study of six incrementally increasing weights at two magnetic strengths was performed. There was no deflection of any of the gold eyelid loads at either 0.5-tesla or 1.5 tesla magnetic strengths. We conclude that patients with gold eyelid weights are not at risk of damage from movement of the prostheses during magnetic resonance imaging examination. PMID- 8357224 TI - Control of hemorrhage during renal failure with triglycyl-lysine-vasopressin. AB - A 35-year-old man with chronic renal failure developed toxic epidermal necrolysis due to combination antibiotic therapy for a community acquired pneumonia. During wound care for his toxic epidermal necrolysis, he developed massive bleeding, a 4 to 6 unit blood loss at each dressing change, due to uremia-associated platelet dysfunction and thrombocytopenia. After failure of standard therapy, the man was treated with intravenous triglycyl-lysine-vasopressin, a selective peripheral vasoconstrictor. Transfusion requirements stopped during treatment. This man went on to full recovery with complete wound healing. Triglycyl-lysine-vasopressin effectively reduced skin blood loss in this man with toxic epidermal necrolysis and an intrinsic hemostatic defect, and may be useful in other patients with cutaneous blood loss. PMID- 8357225 TI - Emergency free flap reconstruction of a facial gunshot wound. AB - An emergency free rectus abdominis myocutaneous flap was used to reconstruct a massive facial gunshot wound with associated cranial communication immediately after the primary debridement. The bony defect was reconstructed with split calvarial and rib grafts, plates, and screws. The free flap provided adequate coverage of the bony reconstruction and separation of the cranial and sinus cavities. PMID- 8357226 TI - Osteoid osteoma of the hamate: report of a case and review of the literature. AB - There are 7 reported patients with osteoid osteoma of the hamate. Only 1 of these has involved the hook of the hamate. This article reports the second patient with osteoid osteoma involving the hook of the hamate. The clinical features, the diagnostic problems, and the management of this lesion are reviewed. PMID- 8357227 TI - Dermatofibrosarcoma protuberans appearing during pregnancy. AB - Dermatofibrosarcoma protuberans is an uncommon skin tumor with a high potential for local recurrence if not adequately excised. There are only two reports in the literature describing dermatofibrosarcoma protuberans that enlarged considerably during pregnancy. On the other hand, the new development or enlargement of dermatofibromas in pregnancy is well documented. We present 2 additional patients in whom a dermatofibrosarcoma protuberans appeared and grew rapidly during pregnancy. Immunohistochemical studies were negative for estrogen and progesterone receptors. The possible pathophysiology and surgical management are presented and discussed. PMID- 8357228 TI - But is it significant? PMID- 8357229 TI - Re: Free muscle transfer for reconstruction after melanoma resection of the leg. PMID- 8357230 TI - Intravascular ultrasound. PMID- 8357231 TI - Imaging for planned hepatic resection. PMID- 8357232 TI - Percutaneous recanalization and stents of the biliary tree. AB - Biliary obstruction can be treated by surgical, endoscopic or percutaneous methods. Interventional radiology has the following recanalization methods to offer: external-internal drainage, balloon dilatation of strictures and permanent stent placement. Metallic expandable stents are becoming very popular. In many centers, endoscopic interventions of the biliary tract have replaced the percutaneous route as a primary procedure. Combined radiologic and endoscopic methods are helpful in complicated interventions. PMID- 8357234 TI - Ultrasound guided drainage of abdominal abscesses and fluid collections. PMID- 8357233 TI - Imaging of the kidney, liver, and pancreas transplant. AB - Imaging of the renal, hepatic, and pancreas allograft is essential for evaluation of postoperative complications. Surgical complications after organ transplantation can generally be specifically diagnosed. These complications include obstruction, leakage, peritransplant fluid collections, and vascular problems such as vascular stenosis or thrombosis, arteriovenous fistula, and pseudoaneurysm. Using computed tomography (CT) or ultrasound guidance, interventional procedures can often be performed to treat various surgical complications. On the other hand, medical causes of allograft transplant dysfunction such as rejection, acute tubular necrosis, drug toxicity, ischemia, infection, inflammation, or the development of recurrent disease are frequently associated with nonspecific imaging findings. Allograft biopsy is still usually necessary for definitive diagnosis in these cases. In this article, we will briefly outline the spectrum of abnormalities that can be seen in the allograft recipient and show some examples of these complications. PMID- 8357236 TI - Surgical aspects of diagnostic and interventional radiology. Special issue. PMID- 8357235 TI - Percutaneous treatment of lumbar disc herniation. AB - Nine hundred and eighteen patients were subjected to percutaneous treatment of lumbar herniated disc. 733 of these were treated through enzymatic nucleolysis with chymopapain, for a total 883 levels (150 of whom were treated at two levels): 185 patients were treated with Onik's automate discectomy. Chemonucleolysis was carried out on 733 patients (79.8%) and automated discectomy in 185 cases (20.1%). Chemonucleolysis has led to the resolution of the symptoms in a high percentage of cases (82.2%). Nucleotomy was an effective method of management in 74.6% of the cases. The availability of several therapeutic methods has allowed us to respond in a more appropriate way to the patient's requirements and, in the case of failure, offer a more flexible therapeutic spectrum, and to consider surgery as the last resort. As regards the relation between enzymatic nucleolysis with chymopapain and disc nucleoaspiration, we feel that the two should not be in competition, for the indications are precise for both methods: in the enzymatic treatment, the hernia can be medium-large sized, in a sub- or extra-ligamentous position. The treatment of patients with moderately severe symptoms is preferable. In disc nucleoaspiration, the hernia must be small-sized. PMID- 8357237 TI - The role of coronary angioplasty in the management of coronary artery disease. AB - Coronary angioplasty is well established as a treatment modality for coronary artery disease. Clinical experience leaves no doubt that it can be very effective in relieving symptoms in patients with unstable angina and with chronic stable angina. There are, at present, no controlled trials to demonstrate its efficacy, though several are under way. In straightforward cases the initial success rate is about 90%, but for each lesion dilated, there is about a 30% chance of significant re-stenosis. Re-stenosis (which is the main chronic complication) usually occurs early--often within a few weeks of the procedure--and it rarely develops later than six months after the procedure. Acute closure of the dilated artery (usually within an hour or two of procedure) is the most feared acute complication and is the main factor contributing to the 0.2% acute mortality rate and to the 1-5% risk of emergency coronary artery bypass grafting. The procedural risk does not increase progressively with serial interventions (in contrast to coronary artery surgery). Furthermore, angioplasty is often undertaken following surgery when stenoses have developed within the grafts, at the graft-vessel anastomosis, in the native vessels distal to the graft insertion or in native ungrafted vessels. Angioplasty is less costly than coronary surgery, although the 30% re-stenosis rate implies a requirement for additional interventions as a result of which the cost differential is not as great it initially appears. PMID- 8357238 TI - Magnetic resonance angiography: current clinical applications. AB - Magnetic Resonance Angiography (MRA) is the newest non-invasive procedure for the evaluation of the vascular system. The basis to obtain images of vessels from Magnetic Resonance (MR) data rely upon the specific signal alteration determined by flowing blood. By using special techniques only these signals are evidenced, with cancelling of the surrounding stationary tissues. Clinical applications are reviewed in this paper. They include: Evaluation of intracranial vessels with important adjunct information to those obtained by conventional MR images; Definition of cerebrovascular disease including the carotid artery with good correlation with Digital Subtraction Angiography (DSA); Evidence of abdominal vessels, with clear imaging of abdominal aortic aneurysms; Definition of renal arteries; although problems exist, the technique may become useful in the future for the screening of renovascular hypertension; Visualization of peripheral vessels; initial results indicate a potential application in the evaluation of peripheral run-off distal to occlusions. PMID- 8357239 TI - Percutaneous recanalisation of arteries. PMID- 8357240 TI - Survival and growth of Escherichia coli O157:H7 on salad vegetables. AB - The influence of modified-atmosphere packaging, storage temperature, and time on survival and growth of Escherichia coli O157:H7 inoculated onto shredded lettuce, sliced cucumber, and shredded carrot was determined. Growth of psychotrophic and mesophilic microorganisms and changes in pH and sensory qualities of vegetables, as judged by subjective evaluation, were also monitored. Packaging under an atmosphere containing 3% oxygen and 97% nitrogen had no apparent effect on populations of E. coli O157:H7, psychotrophs, or mesophiles. Populations of viable E. coli O157:H7 declined on vegetables stored at 5 degrees C and increased on vegetables stored at 12 and 21 degrees C for up to 14 days. The most rapid increases in populations of E. coli O157:H7 occurred on lettuce and cucumbers stored at 21 degrees C. These results suggest that an unknown factor(s) associated with carrots may inhibit the growth of E. coli O157:H7. The reduction in pH of vegetables was correlated with initial increases in populations of E. coli O157:H7 and naturally occurring microfloras. Eventual decreases in E. coli O157:H7 in some samples, e.g., those stored at 21 degrees C, are attributed to the toxic effect of accumulated acids. Changes in visual appearance of vegetables were not influenced substantially by growth of E. coli O157:H7. The ability of E. coli O157:H7 to growth on raw salad vegetables subjected to processing and storage conditions simulating those routinely used in commercial practice has been demonstrated. PMID- 8357241 TI - Purification and preliminary characterization of permethrinase from a pyrethroid transforming strain of Bacillus cereus. AB - Bacillus cereus SM3 was isolated on a mineral salts medium with Tween 80 as the primary carbon source. It was able to hydrolyze second- and third-generation pyrethroids, thereby generating noninsecticidal products. The enzyme responsible for this hydrolytic reaction was named permethrinase for this study. This is the first instance in which pyrethroid detoxification has been achieved with a cell free microbial enzyme system. Permethrinase was purified by ion-exchange chromatography and gel filtration chromatography. The molecular mass of native permethrinase was 61 +/- 3 kDa, as estimated by Sephadex G-100 gel filtration. This novel microbial esterase seems to be a carboxylesterase. Permethrinase activity had an optimum pH of 7.5 and a temperature optimum of 37 degrees C. No cofactors or coenzymes were required for permethrinase activity. The enzyme may be a serine esterase, as it seems to be sensitive to the organophosphorus compound tetraethylpyrophosphate at concentrations in the micromolar range. Addition of dithiothreitol afforded permethrinase protection against the inhibitory effects of the sulfydryl agents p-chloromercuribenzoate and N ethylmaleimide. The enzyme was stable over a range of temperatures. Cell extracts of strain SM3 also contained another esterase, which was active towards beta naphthylacetate, but this enzyme was distinct from permethrinase. PMID- 8357242 TI - Isolation and characterization of the lantibiotic salivaricin A and its structural gene salA from Streptococcus salivarius 20P3. AB - A bacteriocin-like inhibitory substance, salivaricin A, was purified from cultures of Streptococcus salivarius 20P3 and was shown by ion spray mass spectrometry to have a molecular mass of 2,315 +/- 1.1 Da. Amino acid composition analysis demonstrated the presence of lanthionine, indicating that salivaricin A may be a member of the lantibiotic class of antibiotic substances. The sequence of eight amino acids at the N terminus of the molecule was determined by Edman degradation, and mixed oligonucleotide probes based on part of this sequence (GSGWIA) were used to detect the salivaricin A structural gene. A 6.2-kb EcoRI fragment of chromosomal DNA from strain 20P3 that hybridized with the probes was cloned, and the hybridizing region was further localized to a 379-bp DraI-AluI fragment. Analysis of the nucleotide sequence of this fragment indicated that salivaricin A is synthesized as a 51-amino-acid prepeptide that is posttranslationally modified and cleaved to give a biologically active 22-residue peptide containing one lanthionine and two beta-methyllanthionine residues. The secondary structure of presalivaricin A was predicted to be similar to that of type A lantibiotics, with a hydrophilic alpha-helical leader sequence and a propeptide region with potential for beta-turn formation and a lack of alpha helicity. The sequence around the cleavage site of presalivaricin A differed from that of other type A lantibiotics but was similar to that of several bacteriocin like inhibitory substances produced by lactic acid bacteria. PMID- 8357243 TI - Combined effects of sulfites, temperature, and agitation time on production of glycerol in grape juice by Saccharomyces cerevisiae. AB - Analysis of variance was used to evaluate the simultaneous effects of strain, incubation temperature (15 to 25 degrees C), agitation time (0 to 24 h), and initial sulfite concentration (100 to 300 ppm) on glycerol production in grape juice by Saccharomyces cerevisiae. Fourteen strains were studied to determine their growth patterns in the presence of sulfites and ethanol. Baker's yeast strains were more sensitive to sulfite than wine strains, and little growth occurred at initial sulfite levels greater than 150 ppm. Sensitivity to sulfite increased with increasing levels of ethanol. Three strains exhibiting the best growth in the presence of sulfites and ethanol were selected for interaction studies. Fermentations were carried out until the solids content had decreased to less than 6 degrees Brix, which was the point that glycerol content became stable. For the three strains used, the greatest level of glycerol production was observed in the presence of 300 ppm of sulfite for most incubation temperatures and agitation times. There was significant interaction between the strain, incubation temperature, and agitation time parameters for glycerol synthesis, and a response surface method was used to predict the optimal conditions for glycerol production. Under static conditions, the highest level of glycerol production was observed at 20 degrees C, while incubation at 25 degrees C gave the best results when the cultures were agitated for 24 h. Response surface equations were used to predict that the optimum conditions for glycerol production by S. cerevisiae Y11 were a temperature of 22 degrees C, an initial sulfite concentration of 300 ppm, and no agitation, which yielded 0.68 g of glycerol per 100 ml. PMID- 8357244 TI - Isolation and characterization of Selenomonas ruminantium strains capable of 2 deoxyribose utilization. AB - Microbes from ruminal contents of cattle were selectively enriched by using 2 deoxyribose (2DR) as a substrate for growth. Bacterial isolates growing on 2DR were gram-negative, curved, motile rods. The isolates grew on a broad range of substrates, including deoxyribose, glucose, ribose, mannitol, and lactate as well as ribonucleosides and deoxyribonucleosides. The strains also grew on rhamnose (6 deoxymannose) but not DNA. Organic acids produced from growth on hexoses and pentoses included acetate, propionate, lactate, and succinate. The isolates were identified as Selenomonas ruminantium subsp. lactilytica on the basis of morphology, substrate specificity, and other biochemical characteristics. Several characterized species of ruminal bacteria were also screened for growth on 2DR, with only one strain (S. ruminantium PC-18) found able to grow on 2DR. Ethanol was produced by 2DR when strains were grown on ribose or 2DR. PMID- 8357245 TI - Sodium chloride, potassium chloride, and virulence in Listeria monocytogenes. AB - Virulence, as determined in a mouse model, and the virulence factor activities of catalase, superoxide dismutase, and listeriolysin O were examined in a parental strain (10403S) and in a nonhemolytic mutant strain (DP-L224) of Listeria monocytogenes. The cells were propagated in media containing various concentrations of sodium chloride or potassium chloride. Strains 10403S and DP L224 exhibited significant increases in catalase activity and listeriolysin O activity when grown in medium containing either salt at 428 mM. The superoxide dismutase activities for both strains increased when they were grown in medium containing either salt. The superoxide dismutase activity was significantly increased only when cells were propagated in medium containing no salt compared with that when they were propagated in medium containing either salt at 1,112 mM. In addition, the listeriolysin O activity was highest for cells propagated in medium containing KCl at 428 mM, while the activity was significantly less for cells propagated in medium containing NaCl at an equal concentration. Virulence was examined in mouse livers and spleens after intravenous infection, and approximate 50% lethal doses were determined after intragastric and intraperitoneal infection. Each method of infection indicated that listeriolysin O is required for virulence, while growth in salt-containing medium or the production of higher levels of catalase, superoxide dismutase, and listeriolysin O do not appear to enhance the virulence of L. monocytogenes. PMID- 8357246 TI - Purification and partial characterization of an elastolytic serine protease of Prevotella intermedia. AB - Elastolytic strains of Prevotella intermedia were isolated from pus samples of adult periodontal lesions. Elastase was found to associate with envelope, and it could be solubilized with guanidine-HCl. The enzyme was purified to homogeneity by sequential procedures including ion-exchange chromatography, gel filtration, and hydrophobic interaction chromatography. This elastase was a serine protease, and its mass was 31 kDa. It hydrolyzed elastin powder, but collagen and azodye conjugated proteins were not degraded by this enzyme. Both synthetic substrates for human pancreatic (glutaryl-L-alanyl-L-alanyl-L-prolyl-L-leucine p nitroanilide) and leukocyte elastase (methoxy succinyl-L-alanyl-alanyl-L-prolyl-L valine p-nitroanilide) were hydrolyzed. PMID- 8357247 TI - Fate of Agrobacterium radiobacter K84 in the environment. AB - Agrobacterium radiobacter K84 is an effective, commercially applied, biological control agent for the plant disease crown gall, yet little is known about the survival and dissemination of K84. To trace K84 in the environment, spontaneous antibiotic-resistant mutants were used. Growth rates and phenotypes of streptomycin- or rifampin-resistant K84 were similar to those of the parental K84, except the rifampin-resistant mutant produced less agrocin 84 as determined by bioassay. K84 and a strain of Agrobacterium tumefaciens established populations averaging 10(5) CFU/g in the rhizosphere of cherry and persisted on roots for 2 years. K84 established rhizosphere populations between 10(4) and 10(6) CFU/g on cherry, ryegrass, and 11 other herbaceous plants. Populations of K84 declined substantially in fallow soil or water over a 16-week period. K84 was detected in the rhizosphere of ryegrass located up to 40 cm from an inoculum source, indicating lateral dissemination of K84 in soil. In gall tissue on cherry, K84 established populations of 10(5) CFU/g, about 10- to 100-fold less than that of the pathogen. These data demonstrate that K84 persists for up to 2 years in a field environment as a rhizosphere inhabitant or in association with crown gall tissue. PMID- 8357248 TI - Effects of medium and trace metals on kinetics of carbon tetrachloride transformation by Pseudomonas sp. strain KC. AB - Under denitrifying conditions, Pseudomonas sp. strain KC transforms carbon tetrachloride (CT) to carbon dioxide via a complex but as yet undetermined mechanism. Transformation rates were first order with respect to CT concentration over the CT concentration range examined (0 to 100 micrograms/liter) and proportional to protein concentration, giving pseudo-second-order kinetics overall. Addition of ferric iron (1 to 20 microM) to an actively transforming culture inhibited CT transformation, and the degree of inhibition increased with increasing iron concentration. By removing iron from the trace metals solution or by removing iron-containing precipitate from the growth medium, higher second order rate coefficients were obtained. Copper also plays a role in CT transformation. Copper was toxic at neutral pH. By adjusting the medium pH to 8.2, soluble iron and copper levels decreased as a precipitate formed, and CT transformation rates increased. However, cultures grown at high pH without any added trace copper (1 microM) exhibited slower growth rates and greatly reduced rates of CT transformation, indicating that copper is required for CT transformation. The use of pH adjustment to decrease iron solubility, to avoid copper toxicity, and to provide a selective advantage for strain KC was evaluated by using soil slurries and groundwater containing high levels of iron. In samples adjusted to pH 8.2 and inoculated with strain KC, CT disappeared rapidly in the absence or presence of acetate or nitrate supplements. CT did not disappear in pH adjusted controls that were not inoculated with strain KC. PMID- 8357249 TI - Hydroxylation and biodegradation of 6-methylquinoline by pseudomonads in aqueous and nonaqueous immobilized-cell bioreactors. AB - Selective culturing of pseudomonads that could degrade quinoline led to enrichment cultures and pure cultures with expanded substrate utilization and transformation capabilities for substituted quinolines in immobilized and batch cultures. Immobilized cells of the pseudomonad cultures rapidly transformed quinolines to hydroxyquinolines in bioreactors and were able to tolerate higher substrate concentrations compared with batch cultures. After prolonged incubation on a mixture of quinoline and 6-methylquinoline, a quinoline-degrading culture of Pseudomonas putida developed the ability to biodegrade 6-methylquinoline, which initially was resistant to microbial attack, as a sole source of carbon and energy. 6-Methylquinoline was also degraded in a nonaqueous solution by this strain of P. putida when a solution of 6-methylquinoline in decane was flowed through an immobilized-cell fixed-bed bioreactor. PMID- 8357250 TI - Direct polymerase chain reaction detection of Campylobacter jejuni and Campylobacter coli in raw milk and dairy products. AB - A polymerase chain reaction (PCR) method designed to sensitively detect and identify Campylobacter jejuni and Campylobacter coli without the need for isolating and culturing strains is described. The intergenic sequence between the flagellin genes flaA and flaB was amplified and characterized with a triple primer or seminested primer approach. A total of 50 bacterial strains, 27 of C. jejuni and C. coli and 23 of other species, were tested, giving no false-positive or false-negative results. The detection limit as determined by ethidium bromide staining of amplification products on agarose gels was 10 bacteria or less in artificially contaminated water, milk, and soft cheese samples with the seminested primer PCR assay. As an application of the PCR system, a set of 93 samples of milk and other dairy products was screened for the presence of C. jejuni and C. coli. We identified six positive samples (6.5%), while none were found with a conventional culture method. PMID- 8357251 TI - Initial-phase optimization for bioremediation of munition compound-contaminated soils. AB - We examined the bioremediation of soils contaminated with the munition compounds 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine, and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetraazocine by a procedure that produced anaerobic conditions in the soils and promoted the biodegradation of nitroaromatic contaminants. This procedure consisted of flooding the soils with 50 mM phosphate buffer, adding starch as a supplemental carbon substrate, and incubating under static conditions. Aerobic heterotrophs, present naturally in the soil or added as an inoculum, quickly removed the oxygen from the static cultures, creating anaerobic conditions. Removal of parent TNT molecules from the soil cultures by the strictly anaerobic microflora occurred within 4 days. The reduced intermediates formed from TNT and hexahydro-1,3,5-trinitro-1,3,5-triazine were removed from the cultures within 24 days, completing the first stage of remediation. The procedure was effective over a range of incubation temperatures, 20 to 37 degrees C, and was improved when 25 mM ammonium was added to cultures buffered with 50 mM potassium phosphate. Ammonium phosphate buffer (50 mM), however, completely inhibited TNT reduction. The optimal pH for the first stage of remediation was between 6.5 and 7.0. When soils were incubated under aerobic conditions or under anaerobic conditions at alkaline pHs, the TNT biodegradation intermediates polymerized. Polymerization was not observed at neutral to slightly acidic pHs under anaerobic conditions. Completion of the first stage of remediation of munition compound-contaminated soils resulted in aqueous supernatants that contained no munition residues or aminoaromatic compounds. PMID- 8357252 TI - Presumptive fecal streptococci in environmental samples characterized by one dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - The use of fecal streptococci as fecal indicators requires better knowledge of the ecology of these bacteria. We isolated 371 presumptive fecal streptococci from environmental samples--domestic wastewater, forest industry wastewater, contaminated surface and seawater, well water, cow dung, bird droppings, and pristine waters--and clustered them according to their protein profiles in one dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Some clusters could be tentatively identified with the help of reference strains. Samples from each environment had a typical composition of streptococcus types. Enterococcus faecalis was present, but not as a dominating enterococcal species, in samples in which fecal contamination was probable. Enterococcus faecium, Enterococcus durans, Enterococcus hirae, and Enterococcus mundtii had protein profiles that were difficult to distinguish from each other. These bacteria were found in a variety of samples. Enterococcus casseliflavus and Enterococcus gallinarum had identical protein profiles. On the basis of the maximum temperatures for growth and pigment production, isolates of this protein profile group common in forest industry wastewaters were identified as E. casseliflavus. Lactococcus lactis subsp. lactis was also found in this environment. Nearly all strains from pristine waters belonged to protein profile groups which could not be identified with the aid of known Aerococcus, Enterococcus, Lactococcus, or Streptococcus strains. The maximum temperatures for growth and the results of fatty acid analysis were in general agreement within each protein profile group. PMID- 8357253 TI - Inhibitory effect against pathogenic and spoilage bacteria of Pseudomonas strains isolated from spoiled and fresh fish. AB - The antibacterial effects of 209 Pseudomonas strains isolated from spoiled iced fish and newly caught fish were assessed by screening target organisms in agar diffusion assays. One-third (67 strains) inhibited the growth of one or several of six target organisms (Escherichia coli, Shewanella putrefaciens, Aeromonas sobria, Pseudomonas fluorescens, Listeria monocytogenes, and Staphylococcus aureus), of which S. aureus and A. sobria were the most sensitive. The inhibitory action was most pronounced among the strains producing siderophores, and the presence of iron eliminated the antibacterial effect of two-thirds of the inhibitory strains. Siderophore-mediated competition for iron may explain the inhibitory activity of these strains. All but nine of the inhibiting strains were found to inhibit the growth of 38 psychrotrophic S. putrefaciens strains isolated from spoiling fish and fish products. Siderophore-containing Pseudomonas culture supernatants inhibited growth of S. putrefaciens, as did the addition of iron chelators (ethylenediamine dihydroxyphenylacetic acid [EDDHA]). In particular, Pseudomonas strains isolated from newly caught and spoiled Nile perch (Lates niloticus) inhibited S. putrefaciens. This suggests that microbial interaction (e.g., competition or antagonism) may influence the selection of a microflora for some chilled food products. PMID- 8357254 TI - Isolation and identification of eight microcystins from thirteen Oscillatoria agardhii strains and structure of a new microcystin. AB - Microcystins (cyclic heptapeptide hepatotoxins), isolated from 13 freshwater Oscillatoria agardhii strains from eight different Finnish lakes by high performance liquid chromatography, were characterized by amino acid analysis, fast atom bombardment mass spectrometry (FABMS), and tandem FABMS (FABMS/collisionary-induced dissociation/MS). All strains produced two to five different microcystins. In total, eight different compounds, of which five were known microcystins, were isolated. The known compounds identified were [D Asp3]MCYST (microcystin)-LR, [Dha7]MCYST-LR, [D-Asp3]MCYST-RR, [Dha7]MCYST-RR, and [D-Asp3,Dha7]MCYST-RR. This is the first time that isolation of these toxins from Oscillatoria spp., with the exception of [D-Asp3]MCYST-RR, has been reported. Three of the strains produced a new microcystin, and the structure was assigned as [D-Asp3,Mser7]MCYST-RR. The structures of two new microcystins, produced as minor components by one Oscillatoria strain, could not be determined because of the small amounts isolated from the cells. Four strains produced [Dha7]MCYST-RR as the main toxin, but [D-Asp3]MCYST-RR was clearly the most abundant and most frequently occurring toxin among these isolates of O. agardhii. PMID- 8357255 TI - Simple solutions to false-positive staphylococcal enterotoxin assays with seafood tested with an enzyme-linked immunosorbent assay kit (TECRA). AB - The TECRA kit, a commercial staphylococcal enterotoxin visual immunoassay kit, is an enzyme-linked immunosorbent assay system which utilizes polyvalent antisera against staphylococcal enterotoxin types A to E. The test is simple and rapid to perform (4 h) and has therefore been widely used for screening purposes. In this study, the TECRA kit produced a number of false-positive reactions with seafood; 25% of 218 samples of seven types of seafood gave false-positive results, particularly shellfish such as mussels (85%), clams (32%), oysters (23%), winkles (20%), and squid (13%). Some nonshellfish samples also gave false-positive results with the TECRA kit (smelt [20%] and trout [10%]). The substance contributing to the false-positive results differed from true staphylococcal enterotoxins in that it was: (i) heat labile, being completely inactivated by heating for 3 min at 70 degrees C, compared with 5% inactivation of true staphylococcal enterotoxins by the same heat treatment, (ii) in a selective reaction with normal rabbit or calf serum (nonspecific reactions were completely abolished by these sera, whereas staphylococcal enterotoxins were not affected), and (iii) incapable of binding to a copper-chelate Sepharose gel (all of the substance remained in the unbound wash fraction, whereas staphylococcal enterotoxins were quantitatively bound to the gel). The false-positive reactions occurring with seafood were not associated with substances produced by microorganisms, since the bacterial isolates from the samples did not give positive results with the TECRA kit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357256 TI - Genetic instability and strain degeneration in Streptomyces rimosus. AB - During a strain selection program to improve oxytetracycline production in Streptomyces rimosus R6, isolates that showed extreme morphological instability appeared. Propagation via spores gave much higher instability than did propagation via mycelial fragments. Five phenotypic traits were affected: sporulation, pigmentation, colony morphology, oxytetracycline production, and oxytetracycline resistance. The variants were classified on the basis of oxytetracycline resistance into three classes. Class I variants (99% of variants) showed parental levels of resistance but were very heterogeneous regarding the other phenotypes. No DNA rearrangements were detected in primary class I variants. Class II variants (1% of variants, oxytetracycline sensitive) were phenotypically uniform, and most variants carried the same large deletion of ca. 455 kb, including the oxytetracycline resistance gene otrB. Class III variants (0.1% of variants, increased oxytetracycline resistance) were phenotypically uniform and overproduced a brown pigment and oxytetracycline. Most of these variants also showed a reproducible large-scale DNA rearrangement, which probably included deletion and a low-level reiteration (three or four copies) of a DNA fragment. "Revertants" of some class I variants show a similar DNA rearrangement to the class III variants, but there is extensive reiteration of sequences of about 200 kb, including the otrB gene. The significance of these results for the problem of strain degeneration and overproduction of antibiotics is discussed. PMID- 8357257 TI - Biodegradation of 4-nitrotoluene by Pseudomonas sp. strain 4NT. AB - A strain of Pseudomonas spp. was isolated from nitrobenzene-contaminated soil on 4-nitrotoluene as the sole source of carbon, nitrogen, and energy. The organism also grew on 4-nitrobenzaldehyde, and 4-nitrobenzoate. 4-Nitrobenzoate and ammonia were detected in the culture fluid of glucose-grown cells after induction with 4-nitrotoluene. Washed suspensions of 4-nitrotoluene- or 4-nitrobenzoate grown cells oxidized 4-nitrotoluene, 4-nitrobenzaldehyde, 4-nitrobenzyl alcohol, and protocatechuate. Extracts from induced cells contained 4-nitrobenzaldehyde dehydrogenase, 4-nitrobenzyl alcohol dehydrogenase, and protocatechuate 4,5 dioxygenase activities. Under anaerobic conditions, cell extracts converted 4 nitrobenzoate or 4-hydroxylaminobenzoate to protocatechuate. Conversion of 4 nitrobenzoate to protocatechuate required NADPH. These results indicate that 4 nitrotoluene was degraded by an initial oxidation of the methyl group to form 4 nitrobenzyl alcohol, which was converted to 4-nitrobenzoate via 4 nitrobenzaldehyde. The 4-nitrobenzoate was reduced to 4-hydroxylaminobenzoate, which was converted to protocatechuate. A protocatechuate 4,5-dioxygenase catalyzed meta-ring fission of the protocatechuate. The detection of 4 nitrobenzaldehyde and 4-nitrobenzyl alcohol dehydrogenase and 4-nitrotoluene oxygenase activities in 4-nitrobenzoate-grown cells suggests that 4-nitrobenzoate is an inducer of the 4-nitrotoluene degradative pathway. PMID- 8357258 TI - Distribution of uidA gene sequences in Escherichia coli isolates in water sources and comparison with the expression of beta-glucuronidase activity in 4 methylumbelliferyl-beta-D-glucuronide media. AB - The uidA gene, which encodes the beta-glucuronidase enzyme, was detected in 97.7% of 435 Escherichia coli isolates from treated and raw water sources by DNA-DNA hybridization; 92.4% of the strains expressed the translational product in 4 methylumbelliferyl-beta-D-glucuronide-containing media after reinoculation. Upon initial isolation from water samples, the minimal medium o-nitrophenyl-beta-D galactopyranoside-4-methylum-belliferyl -beta-D-glucuronide preparations failed to detect more than 50% of the E. coli isolates that possessed uidA gene. Treated water gave the lowest recovery, with Colilert producing 26% positive samples and Coliquik producing 48% positive samples. There appears to be no relationship between the intensity of the autoradiographic signals of the uidA gene and the expression of beta-glucuronidase activity. Therefore, another variable such as physiological condition of the bacteria could be responsible for the nonexpression of the enzyme activity. PMID- 8357259 TI - Microcosm and in situ field studies of enhanced biotransformation of trichloroethylene by phenol-utilizing microorganisms. AB - The ability of different aerobic groundwater microorganisms to cometabolically degrade trichloroethylene (TCE), 1,2-cis-dichloroethylene (c-DCE), and 1,2-trans dichloroethylene (t-DCE) was evaluated both in groundwater-fed microcosms and in situ in a shallow aquifer. Microcosms amended with phenol or toulene were equally effective in removing c-DCE (> 90%) followed by TCE (60 to 70%), while the microcosm fed methane was most effective in removing t-DCE (> 90%). The microcosm fed ammonia was the least effective. None of the microcosms effectively degraded 1,1,1-trichloroethane. At the Moffett Field groundwater test site, in situ removal of c-DCE and TCE coincided with biostimulation through phenol and oxygen injection and utilization, with c-DCE removed more rapidly than TCE. Greater TCE and c-DCE removal was observed when the phenol concentration was increased. Over 90% removal of c-DCE and TCE was observed in the 2-m biostimulated zone. This compares with 40 to 50% removal of c-DCE and 15 to 25% removal of TCE achieved by methane-grown microorganisms previously evaluated in an adjacent in situ test zone. The in situ removal with phenol-grown microorganisms agrees qualitatively with the microcosm studies, with the rates and extents of removal ranked as follows: c-DCE > TCE > t-DCE. These studies demonstrate the potential for in situ TCE bioremediation using microorganisms grown on phenol. PMID- 8357260 TI - Biodegradation of ortho-cresol by a mixed culture of nitrate-reducing bacteria growing on toluene. AB - A mixed culture of nitrate-reducing bacteria degraded o-cresol in the presence of toulene as a primary growth substrate. No degradation of o-cresol was observed in the absence of toluene or when the culture grew on p-cresol and 2,4 dimethylphenol. In batch cultures, the degradation of o-cresol started after toluene was degraded to below 0.5 to 1.0 mg/liter but continued only for about 3 to 5 days after the depletion of toluene since the culture had a limited capacity for o-cresol degradation once toluene was depleted. The total amount of o-cresol degraded was proportional to the amount of toluene metabolized, with an average yield of 0.47 mg of o-cresol degraded per mg of toluene metabolized. Experiments with [ring-U-14C]o-cresol indicated that about 73% of the carbon from degraded o cresol was mineralized to CO2 and about 23% was assimilated into biomass after the transient accumulation of unidentified water-soluble intermediates. A mathematical model based on a simplified Monod equation is used to describe the kinetics of o-cresol degradation. In this model, the biomass activity toward o cresol is assumed to decay according to first-order kinetics once toluene is depleted. On the basis of nonlinear regression of the data, the maximum specific rate of o-cresol degradation was estimated to be 0.4 mg of o-cresol per mg of biomass protein per h, and the first-order decay constant for o-cresol-degrading biomass activity was estimated to be 0.15 h-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357261 TI - In situ identification of bacteria in drinking water and adjoining biofilms by hybridization with 16S and 23S rRNA-directed fluorescent oligonucleotide probes. AB - Free-water-phase and surface-associated microorganisms from drinking water were detected and roughly identified by hybridization with fluorescence-labeled oligonucleotide probes complementary to regions of 16S and 23S rRNA characteristic for the domains Bacteria, Archaea, and Eucarya and the beta and gamma subclasses of Proteobacteria. Samples of glass-attached biofilms and plankton were taken from a Robbins device installed in a water distribution system. More than 70% of the surface-associated cells and less than 40% of the planktonic cells visualized by 4',6-diamidino-2-phenylindole staining bound detectable amounts of rRNA-targeted probes. These findings are an indication for higher average rRNA content and consequently higher physiological activity of the attached microbial cells compared with the free-living cells. All detectable cells hybridized with the bacterial probe, whereas no Archaea and no Eucarya cells could be detected. Simultaneous hybridization with probes specific for the beta and gamma subclasses of Proteobacteria revealed that microcolonies already consisted of mixed populations in early stages with fewer than 50 cells. These observations provide further evidence that the coexistence and interaction of bacteria in drinking water biofilms may be an integral part of their growth and survival strategies. PMID- 8357262 TI - Estimation of ruminal bacteriophage numbers by pulsed-field gel electrophoresis and laser densitometry. AB - To investigate phage activity in the rumen, a method for quantifying phage has been developed. By differential centrifugation and ultrafiltration, phage particles were separated and concentrated from ruminal fluid. Linear double stranded DNA from this fraction containing predominantly tailed phage was isolated and separated by size, using pulsed-field gel electrophoresis (PFGE). Laser densitometry of gel photographs allowed the numbers of phages with DNA in each size region to be calculated and, therefore, the total numbers per milliliter of ruminal fluid to be estimated. Phage numbers were estimated to be between 3 x 10(9) and 1.6 x 10(10) particles ml of ruminal fluid-1. The phage population, as gauged by the appearance of DNA on PFGE gels, had two major components. A broad region of DNA between 30 and 200 kb was always present on PFGE gels. It appears this region comprises DNA from a great many different phages and would include most of the temperate phages. In addition, discrete DNA bands ranging in size from 10 to 850 kb were frequently observed. DNA from one such band, of 12 kb in size, was shown to consist primarily of a single DNA type, suggesting that it originated from a specific phage. It is postulated that the discrete bands are due to epidemics or blooms of phage activity from specific, probably lytic, phages. The method that has been developed will greatly enhance future investigations into the interactions between the ruminal phage population, the ruminal bacterial population, and animal nutrition and growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357263 TI - Effect of treated-sewage contamination upon bacterial energy charge, adenine nucleotides, and DNA content in a sandy aquifer on Cape Cod. AB - Changes in adenylate energy charge (ECA) and in total adenine nucleotides (A(T) and DNA content (both normalized to the abundance of free-living, groundwater bacteria) in response to carbon loading were determined for a laboratory-grown culture and for a contaminated aquifer. The latter study involved a 3-km-long transect through a contaminant plume resulting from continued on-land discharge of secondary sewage to a shallow, sandy aquifer on Cape Cod, Mass. With the exception of the most contaminated groundwater immediately downgradient from the contaminant source, DNA and adenylate levels correlated strongly with bacterial abundance and decreased exponentially with increasing distance downgradient. ECAS (0.53 to 0.60) and the ratios of ATP to DNA (0.001 to 0.003) were consistently low, suggesting that the unattached bacteria in this groundwater study are metabolically stressed, despite any eutrophication that might have occurred. Elevated ECAS (up to 0.74) were observed in glucose-amended groundwater, confirming that the metabolic state of this microbial community could be altered. In general, per-bacterium DNA and ATP contents were approximately twofold higher in the plume than in surrounding groundwater, although ECA and per-bacterium levels of A(T) differed little in the plume and the surrounding uncontaminated groundwater. However, per-bacterium levels of DNA and A(T) varied six- and threefold, respectively, during a 6-h period of decreasing growth rate for an unidentified pseudomonad isolated from contaminated groundwater and grown in batch culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357264 TI - Brochocin-C, a new bacteriocin produced by Brochothrix campestris. AB - Brochotrix campestris ATCC 43754 produces a bacteriocin inhibitory towards Brochothrix thermosphacta, lactobacilli, Listeria spp., and other gram-positive bacteria. This antimicrobial agent is heat stable, sensitive to proteases, catalase insensitive, and free of organic acids. No phage particles were detected by transmission electron microscopy. Muramidase activity was not detected in the preparations. On the basis of established criteria, the antimicrobial agent was classified as a bacteriocin and named brochocin-C. PMID- 8357265 TI - Degradation of dicamba by an anaerobic consortium enriched from wetland soil. AB - The biodegradability of dicamba was investigated under anaerobic conditions with a consortium enriched from wetland soil. Degradation proceeded through an initial demethylation reaction, forming 3,6-dichlorosalicylic acid, followed by reductive dechlorination, forming 6-chlorosalicylic acid. The consortium, consisting of a sulfate reducer, three methanogens, and a fermenter, was unable to mineralize the aromatic ring. PMID- 8357266 TI - Is an activator protein-2-like transcription factor involved in regulating gene expression during nitrogen limitation in fungi? AB - The upstream sequences of all published lignin peroxidase and manganese peroxidase genomic clones from Phanerochaete chrysosporium were analyzed. This analysis revealed the presence of putative activator protein-2 (AP-2) recognition sequences in 11 of 15 lignin peroxidase genes. The lignin peroxidase clone GLG6 and the manganese peroxidase gene (mnp-1) have two copies of putative AP-2 sequence in the upstream region. Interestingly, the lignin peroxidase gene VLG4 of another white rot fungus, Trametes versicolor, and the nit-2 gene of Neurospora crassa also contain putative AP-2-binding sequences. Since all of these genes are regulated by nutrient nitrogen, I hypothesize that an AP-2-like transcription factor may be involved in inducing gene expression during nitrogen limitation in fungi. PMID- 8357267 TI - Colony immunoblot assay of botulinal toxin. AB - Botulinal neurotoxin in and around colonies of Clostridium botulinum types A, B, and E and of toxigenic Clostridium butyricum was detected by an enzyme-linked immunoassay procedure whereby the toxin was transferred from the agar medium to a nitrocellulose support and the immobilized toxin was probed with type-specific antibodies. The method identified the toxin types of the colonies grown from a mixed inoculum of C. botulinum serotypes. The specificity of the antitoxins for type A and B toxins was improved by adsorption of the antitoxins with the antigens of heterologous type cultures. PMID- 8357268 TI - Enzymatic determination of itoic acid, a Bacillus subtilis siderophore, and 2,3 dihydroxybenzoic acid. AB - A specific enzymatic method to determine the amounts of itoic acid, a Bacillus subtilis siderophore, and 2,3-dihydroxybenzoic acid (2,3-DHBA) was devised. A sample was incubated first with hippurate hydrolase and then with 2,3-DHBA-3,4 dioxygenase. Itoic acid was estimated from the increase in A374. The incubation with the first enzyme was omitted for the determination of 2,3-DHBA. PMID- 8357269 TI - Associations of London, England, daily mortality with particulate matter, sulfur dioxide, and acidic aerosol pollution. AB - During the extreme pollution episodes of 1952 and 1962 in London, England, excesses in daily mortality were clearly evident. In this study, we examined daily British Smoke, sulfur dioxide, acid aerosols, and weather variables for their short-term associations with daily mortality in the more typical (nonepisodic) winters of 1965-1972. Consideration of the acid aerosol data was of special interest because this chemical component has been suspected as a causal agent in past episodes. Temporal lag structures between the variables were examined after removal of long-term components from each series in order to obtain "rational" cross-correlations. Significant associations between same-day and lagged pollution variables and mortality were found. Alternative regression models with pollution and weather variables were also developed. The coefficients obtained were applied to the 1962 pollution episode to examine the continuity of the estimated slopes. The pollution-predicted deaths fit the observed deaths well, which supports the applicability of such deviation-derived coefficients to the absolute scale. These models were also employed to estimate mean excess daily deaths attributed hypothetically to air pollution. On average, mean effect ranged from 2-7% of all deaths during the nonepisodic winters in Greater London, but the 95% confidence intervals of these estimates overlapped for all model specifications examined. This estimated pollutant mixture "effect" cannot be attributed to a particular pollutant because of a lack of quantitative information on the relative downward biases caused by both analytical errors and errors in the spatial representativeness of each respective pollution index. PMID- 8357270 TI - The hair-organ relationship in mercury concentration in contemporary Japanese. AB - The hair-organ relationship of mercury concentration was investigated in 46 autopsy samples in Tokyo, Japan. Hair mercury levels were highly significantly correlated with organ Hg levels in the cerebrum, cerebellum, heart, spleen, liver, kidney cortex, and kidney medulla, when the total mercury or methyl mercury value in the organ was compared with the hair total mercury or organic mercury, respectively. When the inorganic mercury value was tested, significant correlations remained, with weaker coefficients in all the organs but the spleen. Stepwise multiple regression analysis evidenced that the hair organic mercury value was the major explanatory variable for the organ total mercury or organ methyl mercury value in all the organs. To explain the organ inorganic mercury value, the hair organic mercury value was the major variable for the cerebrum and kidney (both cortex and medulla), the hair inorganic mercury value was the major variable for the cerebellum and heart, and the hair phosphorous and hair organic mercury were the major variables for the liver; no explanatory variable existed for the spleen. Auxiliary explanatory variables accounted for the organ total mercury and inorganic mercury levels, among which the hair selenium value was conspicuous with negative regression coefficients. PMID- 8357271 TI - Questionnaire data as predictors of urinary cotinine levels among nonsmoking adolescents. AB - The strength of association between urinary cotinine and questionnaire data on passive smoking among 542 adolescents was evaluated. There were 103 individuals with urinary cotinine higher than 30 ng/ml; they were compared with all other subjects. The single variable that best predicted the urinary cotinine level was maternal smoking. A strong effect was made by house size and, consequently, house crowding. Maternal smoking and house crowding had a synergic effect. The subject's perception of passive smoking at home also was an independent indication of a high cotinine level. The final model had a fairly good sensitivity, whereas the specificity was somewhat lower. The results suggest that maternal smoking, house crowding, and subject's perception of a smoky environment could be surrogate indices of high passive smoking exposure in this age group and could be useful for epidemiologic studies. PMID- 8357273 TI - Increased risk of esophageal cancer among workers exposed to combustion products. AB - Alcohol and tobacco habits have been identified as strong risk factors for esophageal cancer. Increased risks of esophageal cancer have also been reported to be associated with occupational exposure to asbestos and various metals, among vulcanization workers, asphalt workers, and workers in the petrochemical industry. Mortality and cancer incidence were investigated in a series of studies of workers exposed to combustion by-products, i.e., chimney sweeps, waste incinerator workers, gas workers, and bus garage workers exposed to diesel exhausts. The SMRs for esophageal cancer ranged from 150-386 in these cohorts, and a combined SMR of 289 (95% C.I. 174-452) was obtained. Available data on smoking habits and indirect indicators of alcohol consumption show that the excess cannot be attributed solely to these factors. It seems likely that occupational exposure to combustion products is associated with an increased risk of esophageal cancer. PMID- 8357272 TI - Evidence for interaction between air pollution and high temperature in the causation of excess mortality. AB - Studies have demonstrated repeatedly that air pollution in Athens is associated with a small but statistically significant increase in mortality. Extremely high air temperatures can also cause excess mortality. This study investigated whether air pollution and air temperature have synergistic effects on excess mortality in Athens. Data concerning the increased number of deaths in July 1987 (when a major "heat wave" hit Greece) were compared to the deaths in July of the 6 previous years. This comparison revealed a greater increase in the number of deaths in Athens (97%), compared to all other urban areas (33%) and to all non-urban areas (27%). Data on the daily levels of smoke, sulfur dioxide, and ozone; the number of deaths that occurred daily; and meteorological variables were collected for a 5-y period. The daily value of Thom's discomfort index was calculated. Multiple linear regression models were used to investigate main and interactive effects of air temperature and Thom's discomfort index and air pollution indices. The daily number of deaths increased by more than 40 when the mean 24-h air temperature exceeded 30 degrees C. The main effects of an air pollution index are not statistically significant, but the interaction between high levels of air pollution and high temperature (> or = 30 degrees C) are statistically significant (p < .05) for sulfur dioxide and are suggestive (p < .20) for ozone and smoke. Similar results were obtained when the discomfort index was used, instead of temperature in the models. PMID- 8357274 TI - Air pollution-type fluorosis in the region of Pingxiang, Jiangxi, Peoples' Republic of China. AB - This paper reports on the epidemiology, environmental factors, geological features, and total amount of fluoride intake by residents of the Pingxiang region in the Peoples' Republic of China where there is a high incidence of endemic fluorosis. The results demonstrate that the type of endemic fluorosis is related to air pollution, the major source of which comes from coal that is burned by the residents in their homes. Air pollution also originates from the small kilns that are used to make bricks and tile. The fluorine content in the coal and mud used to mix the coal is considerably high; the content in the mud used as adobe for tiles exceeds 10,000 mg/kg. During the process of burning coal or baking bricks or tiles, a large amount of nonsoluble fluorine is converted into water-soluble fluoride, which can have major human health effects. PMID- 8357275 TI - Chloroform in alveolar air of individuals attending indoor swimming pools. AB - Alveolar air samples were collected from 163 subjects at indoor swimming pools and from 77 nonexposed subjects. Chloroform was present in all samples collected from exposed subjects (median = 695.02 nmol/m3). It was found at very low levels in 53% of samples from nonexposed subjects. Alveolar air chloroform levels from people attending indoor swimming pools (mean value within each sampling session) were correlated with environmental air concentration (r = 0.907, p = .002). Analysis of variance showed that levels of chloroform in alveolar air depend on environmental air concentration, age, intensity of the sport activity, and kind of swimming. Chloroform levels in samples collected from competitive swimmers versus nonswimming visitors were different (F = 10.911, p = .001). Moreover, their pattern of swimming may affect chloroform concentration in alveolar air. The analysis of chloroform in alveolar air assesses indoor exposure in healthy subjects simply and at low cost. PMID- 8357276 TI - Acute myeloid leukemia among petrol station attendants. AB - The risk of acute myeloid leukemia (AML) within different occupations was studied, using occupational information obtained from the Swedish 1970 census. Follow-up in the Swedish Cancer Register was carried out from 1971 to 1984. Among male petrol station attendants, 10 cases were observed versus 2.8 expected (observed/expected = 3.6, 95% confidence interval 1.7-6.6). For several decades, Swedish petrol has contained 3-5% of benzene. Thus, a hypothesis was that benzene had contributed to the excess risk. The work histories of the 10 cases were reconstructed through interviews with surviving relatives and were compatible with the hypothesis. However, because the air benzene exposures at petrol stations always have been lower than benzene exposures associated previously with an increased risk of AML, the leukemogenic effect of benzene may have been potentiated by other petrol or vehicle exhaust components. PMID- 8357277 TI - Hypersensitivity pneumonitis resulting from Aspergillus fumigatus in a greenhouse. AB - A 57-y-old female who had cultivated vegetables in a plastic greenhouse developed a case of hypersensitivity pneumonitis from Aspergillus fumigatus. This report exemplifies a potential hazard caused by a thermotolerant fungus, A. fumigatus, in a poorly constructed greenhouse. PMID- 8357278 TI - Evaluation of the relationship between heart rate and ventilation for epidemiologic studies. AB - Estimation of pulmonary exposure and dose in air pollution epidemiology has been impaired by the lack of methods for directly measuring ventilation in ambulatory subjects. Heart-rate monitoring offers an approach to estimate ventilation by using ventilation-on-heart-rate (VE-HR) regressions established during exercise testing to estimate ventilation in the field. Conventional methods and protocols for testing were used to evaluate the relationship between VE and HR during three tasks: (1) exercising on a cycle ergometer, (2) lifting, and (3) vacuuming. The relationship between VE and HR was curvilinear and was best fit with linear regression models, using a natural log transformation of VE. Considerable interindividual variability in slopes and intercepts was observed across all types of exercise tests. The variability about the fitted regression lines for individual subjects was minimal; for example, individual R2 values for the maximum exercise test on 15 men ranged from 0.90 to 0.99 (mean = 0.97). The regression slopes established during upper-body exercise were greater by approximately 30%, relative to those derived in lower-body exercise (paired t test, p < .001). However, VE-HR regression slopes derived from tests in which progressively increasing workloads were used were comparable to those obtained during variable and nonprogressive protocols. These findings indicate that predictive accuracy is maximized by deriving VE-HR regressions for individual subjects and for both lower- and upper-body activities. PMID- 8357279 TI - Experimental model of lead nephropathy. III. Continuous low-level lead administration. AB - We sought to determine whether continuous low-level lead exposure (100 ppm lead acetate in drinking water) for periods of 1, 3, 6, 9, or 12 mo would produce adverse effects on kidney function or morphology in rats. Maximum blood lead levels in experimental animals were reached at 3 mo and averaged 29.4 +/- 4.1 micrograms/dl. Glomerular filtration rate, determined by single-injection 125I iothalamate clearance, was found to be significantly increased above pair-fed controls at 1 and 3 mo, but it was normal at other time periods. Levels of urinary N-acetyl-beta-D-glucosaminidase exceeded levels found in controls at all time periods, except at 12 mo, when the normal increase with aging obscured differences between experimental animals and controls. In contrast, urinary ligandin (glutathione S transferase), a more specific marker of metal-associated proximal tubular injury, was normal at all time periods. Proximal tubular nuclear inclusion bodies were sparse and were observed only at 1 and 3 mo. There were no other pathological alterations in the kidneys, except at 12 mo, at which time mild tubular atrophy and interstitial fibrosis were seen. Therefore, low-level lead exposure in rats produced no significant changes in renal function and produced only mild alterations in renal morphology after 12 mo. The absence of changes in urinary ligandin accorded with the relative absence of morphological changes, whereas the observed increases in urinary N-acetyl-beta-D glucosaminidase suggest that this enzyme may be an overly sensitive indicator of tubular injury. PMID- 8357280 TI - Hepatorenal syndrome. New perspectives in pathogenesis and treatment. AB - Hepatorenal syndrome is a life-threatening complication of severe liver disease. It is generally accepted that the syndrome is the final stage of complex hemodynamic derangements associated with portal hypertension, ie, peripheral arterial vasodilation, effective hypovolemia, and hyperkinetic status. In spite of reduced systemic resistances, intrarenal vascular resistances are increased. This is probably the consequence of the activation of systemic vasoactive factors, such as the renin-angiotensin system, the sympathetic nervous system, and vasopressin aimed at restoring arterial filling pressure. Recently, it has been shown that intrarenal vasoconstrictors, such as leukotrienes and endothelins, are activated with the progression of liver disease. The renal vasoconstriction is counterbalanced by the intrarenal hyperproduction of vasodilating prostaglandins and kallikreins. When this balance is lost, for whatever mechanism, the renal vascular resistances dramatically increase and the hepatorenal syndrome develops. In spite of increased knowledge about pathogenesis, the treatment of hepatorenal syndrome remains unresolved. Low-dose dopamine or ornipressin are currently employed in many liver units to avoid further deterioration of renal function in patients with severe liver disease who are waiting for liver transplantation that remains, at present, the only effective treatment for hepatorenal syndrome. PMID- 8357281 TI - Ketoconazole and fluconazole drug interactions. AB - This article reviews potential drug interactions that exist between ketoconazole or fluconazole and other drugs. English-language data sources included human subjects' computerized databases and published indexes. Case reports and studies demonstrate decreased dosage requirements of cyclosporine sodium, methylprednisolone sodium succinate, and possibly anticoagulants and phenytoin after ketoconazole or fluconazole administration, suggesting hepatic enzyme inhibition. Increased dosage requirements of ketoconazole are necessary after rifampin administration, suggesting rifampin's induction of hepatic microsomal enzymes. Possibly a similar effect may occur with concomitant fluconazole and rifampin. The effect of ketoconazole administration on prednisolone sodium phosphate and theophylline warrants further study. Fluconazole, a more selective agent for fungal P-450, seems to be of less concern regarding the potential for drug interactions than ketoconazole. PMID- 8357282 TI - DNA screening for breast/ovarian cancer susceptibility based on linked markers. A family study. AB - BACKGROUND: Linkage to chromosome 17q has been identified in hereditary breast cancer and hereditary breast/ovarian cancer syndrome. A hereditary breast/ovarian cancer syndrome kindred was identified that yielded a highly significant lod score (4.20) when 17q markers were studied, enabling us to identify those who probably carried the cancer-associated gene among the high-risk members of the family. METHODS: High-risk members of the hereditary breast/ovarian cancer syndrome kindred were offered counselling on the basis of 17q markers. Family members responding positively received one-to-one genetic counseling in a structured setting. Subjects were educated before disclosure, and the immediate impact of this information was assessed after disclosure. RESULTS: We provided genetic counseling on the basis of linkage findings to 32 relatives (four men and 28 women). Women who were told they were linkage positive expressed an increased motivation for surveillance and prophylactic surgery. Most women who were told they were linkage negative indicated that they would not proceed with prophylactic surgery but would continue careful surveillance. To date, there has been no evidence of serious emotional disturbances resulting from this disclosure. We believe that this experience can be used by cancer geneticists and physicians in developing protocols for genetic counseling in cancer-associated hereditary disorders. CONCLUSIONS: Physicians must understand current developments in cancer genetics and linkage so that they can be applied to genetic counseling and treatment of high-risk patients. PMID- 8357283 TI - Evaluating chest pain. The patient's presentation style alters the physician's diagnostic approach. AB - BACKGROUND: Clinical prediction rules rely largely on objective data to estimate coronary artery disease (CAD) likelihood. However, characterization of chest pain, which is central to such prediction rules, depends in part on a physician's subjective judgments. We performed a clinical trial to assess the influence of the patient's presentation style on the physician's approach to evaluating chest pain. METHODS: Forty-four internists were randomized to one of three treatment groups. Two groups viewed videotapes of the same actress performing the role of a patient in a scripted physician-patient interview in two distinct styles: one group saw a "histrionic" characterization, the other a "businesslike" portrayal. The interviewer was not seen or heard by the subjects; they saw only words on the screen. The third group read a verbatim transcript of the interview. After their initial CAD-likelihood estimates and impressions of probable cause for the patient's symptoms, which were based on history only, the participants in all three groups were given the same laboratory data and a second CAD-likelihood estimate was made. Finally, recommendations for further workup were elicited. RESULTS: Initial diagnostic impressions differed dramatically: a cardiac cause was suspected by 50% of physicians viewing the businesslike portrayal but by only 13% of those viewing the histrionic portrayal. Likewise, those viewing the histrionic and businesslike videos provided different CAD-likelihood estimates initially (10% vs 20%). However, after the patient's laboratory data were revealed, the difference in CAD-likelihood estimates was no longer significant. Despite their making a similar risk appraisal after receiving all of the data, internists viewing the histrionic portrayal were far less likely to pursue a cardiac workup (53% vs 93%). CONCLUSIONS: Although physicians may evaluate patients who have the same history word for word and the same laboratory data and whom they regard as having nearly identical likelihoods of CAD, the physician's ultimate diagnostic approach can be profoundly affected by the patient's presentation style. PMID- 8357284 TI - Factors influencing physicians in recommending in-hospital cardiopulmonary resuscitation. AB - BACKGROUND: Cardiopulmonary resuscitation (CPR) is a dramatic, costly, and often futile intervention whose appropriate use is under scrutiny. Physicians often ask patients and families to make decisions about resuscitation for themselves or loved ones. Clinical variables and personal beliefs may influence physician recommendations about CPR. METHODS: Physicians (N = 451) at a tertiary care hospital were surveyed to determine the following: (1) the factors they consider when recommending in-hospital CPR, (2) the conditions under which they discuss CPR with patients, (3) their recent participation in CPR attempts, (4) their perceptions of its effectiveness, (5) their personal wishes regarding their own resuscitation, and (6) their personal and professional characteristics. RESULTS: The patient's self-reported wishes about resuscitation and physician judgment of medical utility were the most important influences on physician recommendations. Most physicians believe that patients with metastatic cancer or late Alzheimer's disease should not be resuscitated. Age alone was not viewed as an important clinical consideration. Guidance from hospital policies and ethics committees had the least influence on physicians. Physicians overestimated the likelihood of survival to hospital discharge after in-hospital CPR by as much as 300% for some clinical situations and predicted an overall success rate of 30%. CONCLUSION: These findings suggest that most physicians are thoughtful and discriminating in their recommendations to patients about CPR. Patient's wishes are of paramount importance, followed by physician judgment of medical utility. However, physicians do overestimate the efficacy of CPR and may thus misrepresent the potential utility of this therapy to patients and their families. PMID- 8357285 TI - Early administration of heme arginate for acute porphyric attacks. AB - BACKGROUND: We investigated the efficacy of early administration of heme arginate in acute porphyric attacks. METHODS: The series consisted of 51 consecutive acute attacks in 22 patients with acute intermittent porphyria and in two patients with variegate porphyria referred to a hospital in France or in Finland. Four attacks were associated with pareses, and 47 attacks were not. Heme in a dose of 250 mg or 3 mg/kg was started within 24 hours after admission in 37 (72.5%) of the attacks and within 4 days in 49 (96%) of the attacks. During all except five attacks, four daily infusions were given. RESULTS: The mean (+/- SD) duration of abdominal or nonabdominal pain was 2.5 +/- 0.97 days, and opiates were stopped an average of 2.8 +/- 0.72 days after the first heme infusion was started. All patients responded. In 46 (90%) of the attacks, the total hospitalization time was 7 days or less. The mean urinary excretion of porphobilinogen decreased to 16.2% +/- 7.7% and that of 5-aminolevulinic acid to 11.6% +/- 5.6% of pretreatment values. The only side effect was moderate thrombophlebitis in one patient. CONCLUSION: Favorable responses in every attack suggest specific effects of heme. In patients with acute attacks, heme therapy should be started immediately on admission. PMID- 8357286 TI - Infectious complications in heart-lung transplantation. Analysis of 200 episodes. AB - BACKGROUND: Infection remains an important cause of morbidity and mortality in heart-lung transplant recipients. This study was designed to assess the frequency, type, and timing of infection in heart-lung transplant recipients. METHODS: A retrospective analysis of 200 episodes of serious infections occurring in 73 heart-lung recipients at Stanford (Calif) University Medical Center between 1981 and 1990. RESULTS: Bacterial infections accounted for half of all infections, with the highest incidence in the first month after transplantation. Fungal infections (14%) were also common in the first month. Cytomegalovirus was the most common viral agent (15%), occurring primarily in the second month after transplantation. Other viruses (herpes simplex, adenovirus, and respiratory syncytial virus) accounted for a further 15% of total infections. Pneumocystis carinii infections were common 4 to 6 months after transplantation, and Nocardia typically infected recipients later than 1 year after transplantation. There was no significant difference in incidence of infections between patients receiving triple (cyclosporine, prednisone, immuran) or double (cyclosporine and prednisone) immunosuppression therapy. Mortality due to infection accounted for 40% of all deaths. CONCLUSIONS: Knowledge of the incidence and timing of infection should help in the prevention, early detection, and initiation of therapy in these patients. PMID- 8357287 TI - A negative trial of inpatient geriatric consultation. Lessons learned and recommendations for future research. AB - PURPOSE: To determine the effectiveness of inpatient interdisciplinary geriatric consultation provided during hospitalization to frail, elderly subjects. SUBJECTS AND SITE: Admission cohort of 197 men admitted from 1985 through 1989, aged 65 years or more, meeting proxy criteria for frailty, living within follow-up area, without terminal illness, and without prolonged nursing home residence. METHODS AND MEASURES: Randomized controlled trial of inpatient geriatric consultation at a tertiary care Veterans Affairs hospital. Differences were determined between groups in the Physical Self-Maintenance Scale, Instrumental Activities of Daily Living, Mini-Mental State Examination, Morale Scale, and nursing home and health care utilization. RESULTS: No differences were seen between groups in any measure after the intervention or during 1 year of follow-up. Intervention implementation may have been incomplete due to compliance and resource availability. CONCLUSIONS: This trial is not definitive in determining whether geriatric consultation is effective or ineffective. Lessons learned from this research indicate that future studies should target frail subjects, include intervention specific measures, and be conducted with direct control of comprehensive resources. PMID- 8357288 TI - Prevalence of hepatitis C in a chemically dependent population. AB - BACKGROUND: Drug abuse is the major risk factor for hepatitis C in the United States. The objective of this study was to determine the prevalence of hepatitis C virus (HCV), to identify risk factors for HCV, and to correlate HCV and liver function in patients presenting for inpatient detoxification of substances of abuse. METHODS: A total of 687 patients were tested for the presence of antibody to HCV (anti-HCV). Histories related to drug use, sexually transmitted diseases, blood transfusion, and human immunodeficiency virus were obtained, as were serum tests for human immunodeficiency virus, syphilis, hepatitis B, aminotransferases, total bilirubin, and alkaline phosphatase. RESULTS: The overall prevalence of anti-HCV was 63%: 68% in men vs 54% in women (P < .001), with no difference by race. Remarkably, 86% of injecting drug users tested positive for anti-HCV. Identified risk factors for anti-HCV were injecting drug use (P < .001), human immunodeficiency virus infection (P = .003), exposure to hepatitis B virus (P < .001), and a positive rapid plasma reagin test (P = .04). Previous transfusion and history of previous infection with gonorrhea or syphilis did not correlate with the presence of anti-HCV. Patients positive for anti-HCV had significant elevations in aspartate aminotransferase and alanine aminotransferase levels when compared with patients negative for anti-HCV: 50.8 vs 36.7 U/L (P = .002) and 56.0 vs 36.9 U/L (P < .001), respectively. CONCLUSION: Injecting drug users have an extremely high prevalence of anti-HCV. This is the first demonstration, to our knowledge, that the presence of anti-HCV in drug users is associated with significantly increased levels of serum aminotransferases. PMID- 8357289 TI - Renal cell carcinoma presenting as polymyalgia rheumatica. Resolution after nephrectomy. AB - Renal cell carcinoma can present as a variety of paraneoplastic, nonmetastatic conditions, including vasculitis. We describe a patient who presented with the polymyalgia rheumatica syndrome but did not respond to a trial of prednisone. An asymptomatic, nonmetastatic renal cell carcinoma was found during this patient's evaluation. Nephrectomy led to resolution of the systemic complaints. Malignancy, in this case, renal cell carcinoma, can present as polymyalgia rheumatica and resolve after surgical removal of the underlying tumor. PMID- 8357290 TI - Severe reversible hyperglycemia as a consequence of niacin therapy. AB - Hypocholesterolemic drug therapy has become a major focus of cardiovascular medicine because recent evidence has demonstrated that optimization of serum lipid levels results in decreased atherosclerotic cardiovascular risk. Niacin, a B-complex vitamin, is capable of lowering total serum cholesterol and triglyceride levels while simultaneously raising serum high-density lipoprotein cholesterol levels. However, the use of niacin can be complicated by the development of hepatotoxicity, hyperuricemia, and modest hyperglycemia. A patient is described who had an excellent lipid response to niacin therapy but developed the previously undescribed complication of severe, life-threatening hyperglycemia. Therefore, despite its low cost and demonstrated efficacy, because of potential very toxic side effects, niacin therapy needs to be carefully monitored. PMID- 8357291 TI - The bedside Valsalva maneuver: a continually overlooked clinical tool. PMID- 8357292 TI - Pheochromocytoma as a cause of blue toes. PMID- 8357293 TI - Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. AB - OBJECTIVES: We evaluated recurrence and survival for 68 patients with malignant melanoma who participated in a 6-week structured psychiatric group intervention 5 to 6 years earlier, shortly after their diagnosis and initial surgical treatment. We also explored the role of several factors as possible predictors of outcome. DESIGN: This was a randomized controlled experimental study. The Cox proportion hazards regression model was used to quantify the relationship between treatment and the outcomes adjusted by the covariates (age, sex, Breslow depth, tumor site, baseline Profile of Mood States Total Mood Disturbance, baseline active behavioral coping, baseline natural killer cell activity, and treatment [ie, group intervention]). The stepwise procedure was used for covariate selection. RESULTS: For control patients, there was a trend for recurrence (13/34) and a statistically significant greater rate of death (10/34) than for experimental patients (7/34 and 3/34, respectively). We found that being male and having a greater Breslow depth predicted greater recurrence and poorer survival. Analysis of multiple covariates found that only Breslow depth and treatment (ie, group intervention) were significant. Adjusting for Breslow depth, treatment effect remained significant. Finally, baseline affective distress and baseline coping were significant psychobehavioral predictors for recurrence and survival. Surprisingly, higher levels of baseline distress as well as baseline coping and enhancement of active-behavioral coping over time were predictive of lower rates of recurrence and death. CONCLUSION: Psychiatric interventions that enhance effective coping and reduce affective distress appear to have beneficial effects on survival but are not proposed as an alternative or independent treatment for cancer or any other illness or disease. However, the exact nature of this relationship warrants further investigation. PMID- 8357294 TI - Alcoholism and major depression in women. A twin study of the causes of comorbidity. AB - BACKGROUND: Although major depression (MD) and alcoholism co-occur in clinical and epidemiologic samples of women more often than expected by chance, the magnitude and causes of this comorbidity are uncertain. METHODS: Personal interviews were conducted with 2163 female twins from a population-based twin registry. Bivariate twin analysis was performed using two definitions of MD and three definitions of alcoholism of varying diagnostic breadth. RESULTS: Odds ratios ranged from 2.7 to 6.0 and were consistently higher using narrower diagnostic criteria for either disorder. Twin analyses found (1) no evidence for familial environmental factors for either MD or alcoholism; (2) significant genetic correlations, ranging from +.4 to +.6, between MD and alcoholism, which were higher using narrower criteria for alcoholism; (3) significant individual specific environmental correlations, ranging from +.2 to +.4, for all but one of the diagnostic combinations, which were higher using narrower criteria for MD. CONCLUSIONS: Comorbidity between MD and alcoholism in women is substantial and appears to result largely from genetic factors that influence the risk to both disorders, but common environmental risk factors also contribute. However, genetic factors exist that influence the liability to MD without influencing the risk for alcoholism and vice versa. Narrowing the diagnostic criteria for MD or alcoholism increases comorbidity, but for different reasons narrow diagnostic criteria for MD increase the environmental sources of comorbidity while narrow diagnostic criteria for alcoholism increase the genetic sources of comorbidity. PMID- 8357295 TI - A pilot Swedish twin study of affective illness, including hospital- and population-ascertained subsamples. AB - OBJECTIVE: We sought to compare the probandwise concordance rate (PRC) for affective illness (AI) in monozygotic (MZ) and dizygotic (DZ) twins in samples ascertained through psychiatric hospitalization vs samples from the general population. METHODS: Twins were ascertained through psychiatric hospitalization for AI from the Swedish Psychiatric Twin Registry or as a matched sample from the population-based Swedish Twin Registry. Lifetime diagnoses were based on a mailed questionnaire containing, in self-report format, DSM-III-R criteria for mania and major depression. Returned questionnaires were obtained from 1484 individuals and both members of 486 pairs, of whom 154 were classified as MZ, 326 as DZ, and six of unknown zygosity. RESULTS: No evidence was found for violations of the equal environment assumption. Using either a narrow or broad diagnostic approach, the risk for AI in cotwins of proband twins was independent of the gender, polarity (ie, unipolar vs bipolar) and mode of ascertainment of the affected proband (ie, via hospitalization vs from the general population). Combining both subsamples, PRC for total AI using narrow diagnostic criteria was 48.2% in MZ and 23.4% in DZ twins. Using broad diagnostic criteria, the parallel figures were 69.7% and 34.9%. The risk for bipolar illness was substantially increased in the cotwins of probands with bipolar AI. CONCLUSIONS: Genetic factors play a major role in the etiology of AI in Sweden, as assessed by self-report questionnaire. Heritable factors appear to be equally important in AI as ascertained in clinical and epidemiological samples. PMID- 8357296 TI - Lifetime DSM-III-R diagnostic outcomes in the offspring of schizophrenic mothers. Results from the Copenhagen High-Risk Study. AB - OBJECTIVES: To perform a long-term prospective follow-up of children at high risk for schizophrenia to identify risk factors for the development of this disorder. DESIGN: Prospective follow-up population study of children of schizophrenic mothers and their matched controls from age 15 years to age 42 years, with multiple diagnostic assessments performed by senior clinicians using structured interviews blindly with respect to the group membership of the subject. PARTICIPANTS: Two hundred seven offspring of schizophrenic mothers and 104 control children without schizophrenic parents matched to the index group on age, sex, paternal socioeconomic status, urban/rural residence, and the amount of time spent during childhood in institutional rearing. MAIN OUTCOME MEASURE: The prevalence of the DSM-III-R disorders during the subjects lifetime. RESULTS: A significant aggregation of schizophrenia (16.2%) and other nonaffective, nonorganic psychosis (4.6%), and Cluster A personality disorders (21.3%) occurred among the offspring of schizophrenic mothers compared with the controls (1.9%, 0.9%, and 5%, respectively). No evidence of increased aggregation of (psychotic and nonpsychotic) affective disorders was noted among the offspring of schizophrenics. CONCLUSION: These results coincide with the results of other family studies in demonstrating a significant and specific familial aggregation of schizophrenia and nonpsychotic schizophrenia spectrum disorders among the biological relatives of schizophrenics. PMID- 8357297 TI - Plasma alprazolam concentrations. Relation to efficacy and side effects in the treatment of panic disorder. AB - A series of 237 patients with DSM-III-diagnosed panic disorder, or agoraphobia with panic attacks, received alprazolam as part of the placebo-controlled Cross National Collaborative Panic Study. After a 1-week drug-free period, alprazolam dosage was titrated upward with the objective of reaching 6.0 mg/d in all patients. At week 3 of treatment, alprazolam plasma levels were significantly correlated with daily dosage (regression slope: 11.7 ng/mL per milligram per day) but with considerable individual variation. Among patients with spontaneous panic attacks, 70% of those with plasma alprazolam levels greater than 20 ng/mL achieved complete remission vs 31% of those with levels less than 20 ng/mL. Situational panic attack remission increased in frequency with increasing plasma levels, but the relationship was not significant. Patient- and physician-rated global improvement and Hamilton Anxiety and Depression Scale score reductions were maximal at 20 to 39 ng/mL, with no further benefit at higher levels. Central nervous system-depressant side effects increased in frequency with higher plasma levels. Between weeks 3 and 8 of treatment, physicians were permitted to adjust dosage (maximum: 10 mg/d) to optimize response. At week 8, the dose-concentration relationship was essentially identical (regression slope: 10.8 ng/mL per milligram per day), but plasma levels were no longer related to efficacy or side effects. Thus, monitoring of plasma alprazolam concentrations may have a clinically useful role during short-term treatment of panic disorder. PMID- 8357298 TI - An epidemiologic study of Gilles de la Tourette's syndrome in Israel. AB - OBJECTIVES: The goal of this study was to estimate the lifetime prevalence of Gilles de la Tourette's syndrome (GTS) in adolescents aged 16 to 17 years. DESIGN: Population-based epidemiologic study. SUBJECTS: Eighteen thousand three hundred sixty-four males and 9673 females aged 16 to 17 years screened for induction into the Israel Defense Force. RESULTS: Of the 28,037 individuals screened, 12 met diagnostic criteria for GTS. The point prevalence in this population was 4.3 +/- 1.2 (mean +/- SE) per 10,000. The 95% confidence interval for this estimate is 1.9 to 6.7 per 10,000. The point prevalence was 4.9 +/- 1.6 per 10,000 for males (95% confidence interval, 1.8 per 10,000) and 3.1 +/- 1.8 per 10,000 for females (95% confidence interval, 0 to 6.6 per 10,000). The rate of obsessive-compulsive disorder (OCD) was significantly elevated among the subjects with GTS (41.7%) compared with the population point prevalence of OCD (3.4) in those without GTS. In contrast, the rate of attention deficit hyperactivity disorder was only 8.3% compared with the population point prevalence of 3.9% in those individuals without GTS. CONCLUSIONS: The prevalence estimates from this population-based study are in agreement with previous results based on surveys of younger children. The sex ratio observed in this study is not as large as reported in previous studies and remains to be explored in other studies of adolescents and adults. PMID- 8357299 TI - Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Application to the NIMH treatment of Depression Collaborative Research Program dataset. AB - Longitudinal studies have a prominent role in psychiatric research; however, statistical methods for analyzing these data are rarely commensurate with the effort involved in their acquisition. Frequently the majority of data are discarded and a simple end-point analysis is performed. In other cases, so called repeated-measures analysis of variance procedures are used with little regard to their restrictive and often unrealistic assumptions and the effect of missing data on the statistical properties of their estimates. We explored the unique features of longitudinal psychiatric data from both statistical and conceptual perspectives. We used a family of statistical models termed random regression models that provide a more realistic approach to analysis of longitudinal psychiatric data. Random regression models provide solutions to commonly observed problems of missing data, serial correlation, time-varying covariates, and irregular measurement occasions, and they accommodate systematic person-specific deviations from the average time trend. Properties of these models were compared with traditional approaches at a conceptual level. The approach was then illustrated in a new analysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program dataset, which investigated two forms of psychotherapy, pharmacotherapy with clinical management, and a placebo with clinical management control. Results indicated that both person-specific effects and serial correlation play major roles in the longitudinal psychiatric response process. Ignoring either of these effects produces misleading estimates of uncertainty that form the basis of statistical tests of hypotheses. PMID- 8357300 TI - Synthesis and evaluation of sulfur-containing glutethimide derivatives for aromatase and desmolase inhibitory activity. AB - Novel sulfur-containing glutethimide derivatives, substituted with either thiol or methylsulfide groups in the ortho/para positions of the aromatic ring, were synthesized and tested for both human placental aromatase and bovine adrenocortical desmolase inhibitory activities. The synthesis was achieved by the chlorosulfonation of gluthethimide, which yielded a 3:1 mixture of the para to ortho sulfonyl chlorides 2a/b. The sulfonyl chlorides of gluthethimide were reduced with Zn/H2SO4 to give the thioglutethimides 3a/b, which in turn were methylated with MeI/EtOH to give the corresponding methylsulfides 4a/b. In comparison to aminoglutethimide (AG), 3a/b and 4a/b were weak inhibitors of aromatase, with 3a/b being more potent than 4a/b. Aromatase inhibition by the thiol compound was pH-dependent; 3a/b was most potent at higher pH (7.4) than at lower (6.6). This suggested that the thiolate form of 4 coordinates with the ferric heme of aromatase. Likewise, both 3a/b were less potent at inhibiting bovine adrenal desmolase than AG. Possible reasons for the surprisingly poor aromatase inhibitor activity of these compounds are discussed. PMID- 8357301 TI - Ketomethylenebestatin: synthesis and aminopeptidase inhibition. AB - The synthesis of (6R,5S,2RS)-6-amino-5-hydroxy-2-isobutyl-4-oxo-7- phenylheptanoic acid (9), a carbaanalogue of the aminopeptidase (AP) inhibitor bestatin (1) is described. This synthesis was carried out by a malonic ester alkylation with the suitably protected halomethyl ketone of (2S,3R)-AHPBA*), followed by a second alkylation with isobutyl bromide of the resulting 4 ketodiester, and subsequent decarboxylation and deprotection. The inhibitory potencies of the 1:1 diastereomeric mixture 9 against AP-B, AP-M and Leu-AP were approximately 10-fold lower than those of bestatin. PMID- 8357302 TI - Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXII: Bisoxazol-, bisimidazol-, bisthiazol- and oligo-1,2,4-thiadiazolimines. AB - One mesoionic 4,4'-propylene-bis-oxazol-5-imine (5), two 2,2'-m-phenylene-bis imidazol-4-imines (9a,b), five 4,4'-benzene-bis-(and tris)-thiazol-2-amines (13a,b, 14a-c) and 14 3,3'-benzene-bis-(and tris)-1,2,4-thiadiazolimines (18a-o) were synthesized and assayed for their antiplatelet and anticoagulant activities. The most potent compound was the tris-thiadiazole derivative 18m which inhibited the aggregation of platelets induced by collagen at a concentration of 10 mumol/L by 50 percent (Born-test). No anticoagulant effects (Quick-test) were observed up to 400 mumol/L. In the thiazolamine series combined antiplatelet and anticoagulant activities were seen. PMID- 8357303 TI - Mammary tumor inhibiting [1,2-bis(2,6-dihalo-3 hydroxyphenyl)ethylenediamine]platinum(II) complexes, III: Relationship between structure and estrogenic activity of the diamine ligands, their sulfatoplatinum(II) and diiodoplatinum(II) complexes. AB - 1,2-Bis(2,6-dihalo-3-hydroxyphenyl)ethylenediamines with 2,6-Cl2, 2-F-6-Cl, 2 Cl,6-F, and 2,6-F2 substituents (meso-1 to meso-4, D,L-1 and D,L-4) and their sulfatoplatinum(II) complexes were tested in the immature mouse uterine weight test. The only complex with marked estrogenic properties proved to be meso-1 PtSO4. Surprisingly its diamine ligand meso-1 was only marginally active. 1H-NMR spectroscopic studies on the 1,2-diphenylethylenediamine ligand reveal that the 2,6-standing Cl-atoms in meso-1 (antiperiplanar phenyl residues) hinder the rotation of the aromatic rings, which results in very stable conformers with different O-O distances owing to the unsymmetric arrangement of the ring substituents. On transformation into the Pt(II) complex the conformations of meso 1 change (synclinal phenyl residues) and a delta and lambda interconversion takes place already at physiological temp. (37 degrees C). This process is accompanied by a rotation of phenyl rings, which is supposed to allow an optimal fit for the formation of hydrogen bridges to the estrogen receptor, resulting in a marked estrogenic activity. The other ligands and complexes are inactive presumably due to a diminished hydrophobic interaction with the estrogen receptor, resulting from their R,R/S,S-configuration or the reduced number of Cl-atoms. PMID- 8357304 TI - A new approach to electrical safety testing of electromedical equipment. AB - The "New Approach" to electrical safety testing in Sir Charles Gairdner Hospital (SCGH) is based on the results and experience we have obtained in carrying out such tests for a period of over twenty years. Until recently our testing was carried out according to the annual procedures as described in Standards Australia recommendations. Test protocol changes have, however, now been made since it seemed from our records that we had been carrying out testing to an extent not justified by our test results. The paper describes the safety testing programme now in place at SCGH. This programme has resulted in substantial reduction in the testing time without, in our opinion, compromises in safety. The main elements in electromedical equipment test procedures are:- Acceptance tests In-Service tests Tests after repair We have found that the main consumer of time in electrical safety testing, aside from the test procedure itself, is gaining access to the equipment. This can be particularly difficult in areas where equipment is in constant use, e.g. in CCU, ICU, Renal Dialysis, Operating Theatres, etc. We have developed an earth integrity meter for the purpose of checking medical equipment without the need to disconnect it from the mains supply or from the patient. By means of this device, together with our new testing protocol, access problems have been largely eliminated. PMID- 8357305 TI - Biomechanical simulations of scoliotic spinal deformity and correction. AB - A new approach to surgical correction of scoliosis has been advanced by us, in the form of simulation of the surgical correction system and technique. For this purpose, we developed a finite-element model of the spinal column (SFEM), applied tractions to it and determined the model stiffness so as to watch the actual spinal geometry. Having patient-simulated this SFEM, we applied to this SFEM corrective forces and determined the optimal set of forces to gain the best correction of the spinal deformity. We then developed a special instrumentation to measure the applied corrective forces during surgery using a particular fixation system. The SFEM corrected geometry was shown to compare favourably with the post-surgical curve. We have now developed an elastic beam-column model (EBCM) to which muscle activation forces, representing asymmetrical paralysis of the vertebral column muscles, can be applied to generate a given scoliotic curve. In that process the stiffness properties of the patient-simulated EBCM are determined. Now on these patient-simulated EBCM(s), identical corrective force systems are applied as developed by the finite-element model (SFEM) and implemented surgically for these patients. It is shown that the EBCM corrected geometries compare favourably with both SFEM corrected geometries as well as with the post-surgical curves for similar corrective force systems. Thus the EBCM can be employed to presurgically simulate scoliolic correction, specify the optimal corrective system of forces so as to gain the best surgical correction. PMID- 8357306 TI - Absorbance measurement with a helium-neon laser for chemical dosimetry. AB - A laser-based system for absorbance measurement has been developed for use in chemical dosimetry as an alternative to the spectrophotometer. The system incorporating a Helium-Neon laser operating at 543.5 nm is designed specifically for measurement of absorbed doses below 10 Gy with the ferrous sulphate-benzoic acid-xylenol orange (FBX) dosimeter. Absorbance measurement for the FBX dosimeter is normally carried out at 540 nm with a spectrophotometer. The performance of the laser-based system in measurement of absorbance is comparable to that of a standard spectrophotometer and it is concluded that the absorbance measurement technique is not the limiting factor in the sensitivity of the FBX dosimeter for absorbed doses below 1 Gy. PMID- 8357307 TI - Integration of 3-D medical imaging and rapid prototyping to create stereolithographic models. AB - This paper describes current research into the creation of solid models which replicate anatomical structures using rapid prototyping techniques. Stereolithography is particularly efficient in the production of highly-complex structures. This technique was applied to the fabrication of a plastic model of a human skull. A geometric definition of the object was obtained by transferring the three-dimensional medical image volume (x-ray CT) and processing the data on a computer graphics workstation. A 3-D biomedical visualisation software package (ANALYZETM) was used to perform segmentation of structures. A 3-D triangular-mesh representation of the selected structure was calculated and converted to a format suitable for processing and construction using stereolithography (SLA). Improvements in the quality of the anatomical model produced will result from improved data processing techniques. Future work is proposed to investigate the influence of imaging parameters and data processing techniques on the resultant plastic models. PMID- 8357308 TI - The validity of the geometric mean method for estimating internal activities in nuclear medicine. AB - The activity of an internal radioactive source may be calculated by comparing the geometric mean of the regional counts in a pair of conjugate gamma camera images with the geometric mean of the counts from a small surface reference source of known activity. Allowance must be made for the effects of differential forward scatter in the detector count rates from the internal and reference sources. The magnitude of these can be predicted, and a suitable correction factor for a given collimator and energy acquisition window calculated by applying a simple count rate build-up model to the observed count rate-depth data for a point and plate source in a water tank. Using a high resolution collimator with 99mTc sources in three sets of phantom trials, the model shows that a scatter build-up correction factor of 1.20-1.22 is suitable for an internal 99mTc source in a typical adult chest or abdomen. PMID- 8357309 TI - Alpha radiation detection using silicon memory chips--preliminary studies. AB - Alpha radiation dosage is an important occupational health factor in the mining of uranium and mineral sands. Alpha radiation induced errors in the data of silicon based memory chips provide the foundation for a new type of sensor, with the potential for affordable and prompt measurement of personal alpha doses. With particular reference to Dynamic Random Access Memories (DRAM) this paper introduces the operating principle of a memory based radiation sensor, which is the error mechanism in silicon integrated circuits. PMID- 8357310 TI - Influence of temperature and metabolic rate on work performance with Canadian Forces NBC clothing. AB - This study examined the effects of environmental temperature and metabolic rate on soldiers' work tolerance time (WTT) while wearing various levels of nuclear, biological, and chemical (NBC) defence protective clothing. There were 23 unacclimatized males (23 +/- 3 years, 76 +/- 8 kg, 1.77 +/- 0.08 m) assigned to exercise at either a light (walking 1.11 m.s-1 0% grade, alternating with lifting 10 kg) or heavy metabolic rate (walking 1.33 m.s-1 7.5% grade, alternating with lifting 20 kg) in an environmental chamber at either 18 degrees C, 50% R.H. (cool) or 30 degrees C, 50% R.H. (warm). Subjects were tested wearing three levels of clothing protection: combat clothing (L); combats and a semi-permeable NBC overgarment (M); combats and NBC overgarment, gloves, boots and respiratory (H). WTT was the time until rectal temperature (Tre) reached 39.3 degrees C, heart rate reached 95% maximum, dizziness or nausea precluded further exercise, or 5 h had elapsed. During the light and cool trials (N = 5), wearing M or H did not impair WTT (277 +/- 47 min). For the light and warm experiments (N = 6), WTT was significantly impaired with H (82.7 +/- 10.6 min). With the heavy and cool condition (N = 6), WTT was reduced with M (240.5 +/- 73.8 min) and H (56.7 +/- 17.9 min). Finally, during the heavy and warm trials (N = 6), WTT was progressively impaired for L (172.5 +/- 52.8 min), M (65.8 +/- 18.2 min), and H (34.0 +/- 9.7 min) levels of protection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357311 TI - Continuous vs. intermittent work with Canadian Forces NBC clothing. AB - This study examined the benefits of work and rest schedules on soldiers' work tolerance (WTT) while wearing various levels of nuclear, biological and chemical (NBC) defence protective clothing in a warm environment (30 degrees C and 50% R.H.). Eight unacclimatized males were assigned to exercise at either a light (walking 1.11 m.s-1 0% grade, alternating with lifting 10 kg) or heavy metabolic rate (walking 1.33 m.s-1 7.5% grade, alternating with lifting 20 kg). Subjects were tested wearing three levels of clothing protection: combat clothing (L); combats and a semi-permeable NBC overgarment with the hood down (M); combats and NBC overgarment, gloves, boots and respirator (H). For each clothing configuration, subjects were evaluated using both a "continuous" exercise protocol and an intermittent work and rest schedule. WTT was defined as the time until rectal temperature (Tre) reached 39.3 degrees C, heart rate reached 95% maximum, dizziness or nausea precluded further exercise, or 5 h had elapsed. Assuming a resting VO2 of 4 ml.kg-1 x min-1 an average metabolic rate was calculated for all trials. A decreasing hyperbolic function described the relationship between WTT and metabolic rate for M and H. These relationships facilitate quantification of appropriate work and rest schedules if the metabolic rate of a task is known. PMID- 8357312 TI - Hemodynamic and hormonal correlates with exposure to lower body negative pressure after 12 hours head-down tilt. AB - Hemodynamic and hormonal responses to lower body negative pressure (LBNP) after 12-h head-down tilt (HDT) were examined to investigate the mechanism of orthostatic intolerance following spaceflight. Ten young healthy male volunteers participated in the experiment. After 6 degrees HDT for 12 h, the tolerance to 1 h continuous -30 mm Hg LBNP was tested. Variables were measured before and after HDT, during LBNP, and 1 and 10 min after LBNP. Significant reduction in leg volume and plasma volume were observed at the end of 12-h HDT (500 ml and 5.5%, respectively). In the tolerant group, stroke volume index (SI) was decreased by 35% after 15 min LBNP, and carotid arterial blood flow (CBF), by 27% at the end of LBNP compared to the pre-LBNP value. Of the 10 subjects, 5 developed presyncope during LBNP; they exhibited remarkable reduction in SI, CBF, and heart rate, and increased secretion of ADH and adrenaline during or just prior to presyncope. This non-tolerant group tended to be hemo-concentrated from the start of the experiment. However, it will require a prospective study to determine if this variable is a reliable predictor of the outcome of the post-HDT LBNP test from data collected at the end of HDT. PMID- 8357313 TI - Hormonal responses during orthostasis following 4 hours of head-down tilt. AB - The purpose of this investigation was to test the hypothesis that endurance exercise trained (ET) subjects would demonstrate a greater reduction in orthostatic tolerance as compared to untrained (UT) subjects following prior exposure to -6 degrees head-down tilt (HDT) because vasoactive hormone and enzyme responses to head-up tilt (HUT) would be decreased following HDT so as to predispose ET subjects to orthostatic intolerance. Six ET subjects (VO2peak = 4.52 +/- 0.20 L/min) were matched for age and height with six UT subjects (VO2peak = 3.26 +/- 0.22 L/min; p < 0.01). After 30 min of supine rest, subjects were exposed to 30 min of head-up tilt (HUT) at 70 degrees, then on a separate occasion, 4 h of HDT (-6 degrees) followed by 30 min of HUT. The HUT involved passive standing for 30 min or until subjects became presyncopal. Blood sampled from the antecubital vein at min 1, 15, and 30, or at presyncope was analyzed for atrial natriuretic peptide (ANP), aldosterone (PA), arginine vasopressin (AVP), plasma renin activity (PRA), and norepinephrine (NE), while BP and HR were continuously monitored. All subjects tolerating 30 min of HUT, after either condition, had significantly increased (p < 0.05) levels of PRA at the 30th min. Following 4 h of HDT, five of six UT subjects and only one of six ET subjects endured 30 min of HUT. The most marked difference during HUT after prior exposure to HDT was a significant increase in AVP (p < 0.05) at the onset of HUT observed only for the UT subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357315 TI - Correlates of military tank simulator sickness. AB - A military tank driving simulator is currently widely used as a training aid for tank drivers. The purpose of this study was to investigate the relationship between possible correlates of simulator sickness and the occurrence of sickness and performance test results among simulator drivers. The average number of motion sickness-like symptoms reported after driving the simulator among subjects with a history of susceptibility to motion sickness was 3.4, significantly higher than the average of 1.6 reported among subjects who did not report previous susceptibility to motion sickness (p < 0.05). Subjects driving the simulator while screen image quality was disturbed had a longer reaction time (42.0 s) than when driving the simulator without screen interferences (18.4 s, p = 0.001). Subjects driving the simulator for a short period had the same number of symptoms as did those driving for a longer period, but had better digit symbol test results. There was no statistically significant association between the development of sickness and tank driving experience. Suggested countermeasures are expected to prevent simulator sickness among some of the simulator trainees and to make simulator training more effective. PMID- 8357314 TI - Changes in the dark focus of accommodation associated with simulator sickness. AB - The relationship between the dark focus of accommodation and simulator sickness, a form of motion sickness, was examined in three experiments. In Experiment 1, dark focus was measured in 18 college students in a laboratory setting before and after they viewed a projected motion scene depicting low altitude helicopter flight. In Experiments 2 and 3, dark focus was measured in pilots (N = 16 and 23, respectively) before and after they "flew" in moving-base helicopter flight simulators with optical infinity CRT visual systems. The results showed that individuals who experienced simulator sickness had either an inward (myopic) change in dark focus (Experiments 1 and 3) or attenuated outward shifts in dark focus (Experiment 2) relative to participants who did not get sick. These results are consonant with the hypothesis that parasympathetic activity, which may be associated with simulator sickness, should result in changes in dark focus that are in a myopic direction. Night vision goggles, virtual environments, extended periods in microgravity, and heads-up displays all produce related visual symptomatology. Changes in dark focus may occur in these conditions, as well, and should be measured. PMID- 8357316 TI - Helmet slippage during visual tracking: the effect of voluntary head movements. AB - The influence of visual tracking on head movement and on the head/helmet system was investigated for two different helmets (a motorcycle helmet and a flying helmet) under static laboratory conditions. Subjects visually refixated between pairs of illuminated targets located at various horizontal (up to 160 degrees) and vertical (up to 90 degrees) distances apart while head position and helmet slippage were measured in azimuth, pitch, roll, X, Y, and Z using a double magnetic coil system. Results showed that for both helmets, root mean square (RMS) head movement increased with refixation distance, especially in the main axis of refixation, and that RMS helmet slippage can be a function of RMS head motion. Further, large individual differences in the degree of head motion were found. These findings may have implications for designers and investigators of helmet-mounted avionics. PMID- 8357317 TI - Acceleration-induced effects on baboon blood chemistry. AB - Gravity-induced loss of consciousness (G-LOC) is known to have occurred in pilots since the early 1920's. Most of the research in this area has shown that G-LOC occurs due to a decrease in cerebral blood pressure and a concomitant reduction in brain perfusion. Since a reduction in cerebral blood flow can cause transient hypoxia, it is important to study the cerebral metabolism during high +Gz exposure. One component of these studies should include measurements of substrate availability and degradative products. In the present study, adult baboons were given multiple high +Gz exposures (2 to 6) using the Armstrong Laboratory human centrifuge. Venous blood was collected by an automatic syringe withdrawal pump before, during and after centrifuge exposures. The concentration of blood gases, glucose and lactate tended to decrease during the centrifuge exposure followed by an increase after the run. Total creatine kinase activity in serum was not significantly altered. These results suggest that during +Gz exposure, anaerobic glycolysis is stimulated resulting in elevated lactate production due to a reduction in cerebral blood flow (CBF). The elevated tissue lactate is released into the central circulation upon resumption of normal CBF (after the termination of centrifuge run). Therefore, the observed decrease in lactate concentration during the run may result from a lag in the release of tissue lactate into the blood due to a reduction in CBF. It is speculated that at high +6 Gz, G-LOC may occur as a protective response to reduce the brain metabolic rate, to maintain energy levels and to prevent severe cellular acidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357318 TI - Perceptual scaling of whole-body low frequency linear oscillatory motion. AB - Evidence that Z-axis oscillation in the Earth-vertical plane is more provocative of motion sickness than the equivalent imposed oscillation acting in the Earth horizontal raises the possibility that horizontal oscillation is perceived as less intense than equivalent vertical oscillation. In Experiment 1, subjects (n = 8) were oscillated through their head Z-axis in both the Earth-vertical and horizontal planes. In Experiment 2, another group (n = 10) were oscillated through their head Y-axis in the Earth-horizontal. Stimuli were 5 cycles of motion at 0.3 Hz ranging in 3.5 dB intervals from 0.19 to 2.15 m.s-2 (Expt. 1) and from 0.1 to 3.98 m.s-2 (Expt. 2). Perceptual scaling of intensity against acceleration was similar irrespective of direction of oscillation in the Earth plane or head-body axis. Displacement tended to be overestimated, this being most marked for the lower acceleration levels in the horizontal condition. Results supported the notion that Stevens' Power Law exponents decrease as a function of increasing stimulus range. Differences in perception of oscillation intensity and displacement do not seem to explain the markedly greater nauseogenic potential of vertical oscillation. PMID- 8357319 TI - Flight crew sleep during multiple layover polar flights. AB - This study investigated changes in sleep after multiple transmeridian flights. The subjects were 12 B747 airline pilots operating on the following polar flight: Tokyo (TYO)-Anchorage (ANC)-London (LON)-Anchorage-Tokyo. Sleep polysomnograms were recorded on two baseline nights (B1, B2), during layovers, and, after returning to Tokyo, two recovery nights were recorded (R1, R2). In ANC (outbound), total sleep time (TST) was reduced and, sleep efficiency was low (72.0%). In London, time in bed (TIB) increased slightly, but sleep efficiency was still reduced. On return to ANC (inbound), there was considerable slow wave sleep (SWS) rebound and multiple awakenings reduced sleep efficiency to 76.8%. Sleep efficiency on R2 was significantly lower than on B1 (t-test, p < 0.05) but not different from R1. To sum up, sleep of aircrews flying multiple transmeridian flights is disrupted during layovers and this effect persists during the two recovery nights. As a result, there is a marked cumulative sleep loss during multi-legs polar route trip in comparison to single leg flights. These findings suggest that following such extensive transmeridian trips, crews should have at least three nights of recovery sleep in their home time zone before returning to duty. PMID- 8357320 TI - Explosive outbreak of gastroenteritis on an aircraft carrier: an infectious disease mass casualty situation. AB - An aircraft carrier experienced 777 cases of acute gastroenteritis while deployed in the eastern Mediterranean over a 16-d period. These cases were noted in the 5,000-man crew, suggesting a cumulative incidence rate of 15%, though many sailors did not seek medical care for their symptoms. The onboard medical department response included epidemiological investigation with unique shipboard facility considerations, development of a treatment plan, and implementation of preventive/educational programs. Implications for nontrauma related mass casualty situations are discussed. Flight surgeons and operational medicine physicians must have a solid foundation in general preventive medicine to fulfill their responsibilities. PMID- 8357321 TI - Determinants of +Gz-related neck pain: a preliminary survey. AB - The aim of the present study was to detect determinants of acute inflight neck pain in a cohort of 27 student fighter pilots frequently exposed to high +Gz forces. Strenuousness of work, job satisfaction, psychological distress, smoking habits, and frequency of muscle strength, muscle endurance, and aerobic training regimens were inquired about by questionnaire. Physical examination determined the subjects' height, body weight, body mass index, head and neck circumference, passive cervical range of motion, grip strength, and isometric strength of neck muscles. The frequency of muscle endurance training was the only possible determinant related to experienced acute inflight neck pain. PMID- 8357322 TI - Coccidioidomycosis: a persistent threat to deployed populations. AB - The world-wide deployability of aircrew members exposes them to a peculiar array of medical problems. Non-immune populations, upon deployment to endemic areas, may present to the deployed flight surgeon with acute, poorly recognizable syndromes, such as acute coccidioidomycosis. Alternatively, the acquisition of the chronic progressive form of coccidioidomycosis in endemic areas may be a problem for the flight surgeon, who may be faced with a poorly recognizable syndrome which first manifests itself weeks to months after the crewmember's return from deployment. We describe three cases of coccidioidomycosis in service members that highlight the difficulty in the diagnosis of this disease. These cases prompted an epidemiologic survey of recent cases of coccidioidomycosis among Air Force beneficiaries, presented here, to better define the impact of this disease on personnel assigned to endemic areas. A brief discussion of the epidemiologic and clinical features of the disease and of the aeromedical disposition of the aviator is presented. PMID- 8357323 TI - Hazardous materials incidents in military aircraft. AB - We evaluated 10 years of reported hazardous cargo incident information from the U.S. Air Force and Naval Safety Centers. In this first of two papers describing the hazardous cargo problems reported by the two services, we describe types of aircraft and types of hazardous cargo involved in incidents not causing aircraft mishaps. Normally, hazardous cargo must be manifested as such and no passengers are allowed on such flights. Unauthorized hazardous cargo was found on military aircraft carrying passengers. The most common problem was fuel spills or fumes. The most frequent cause of a hazardous cargo incident was improper manifest of same. Improvements are recommended for the incompatible or inconsistent hazardous cargo incident reporting systems, in order to improve prevention of hazardous cargo incidents. PMID- 8357324 TI - Physiological problems caused by transportation of hazardous cargo in military aircraft. AB - This is the second of two articles describing reported incidents involving hazardous cargo on U.S. military aircraft over a 10-year period. In this article, we describe the various physiological responses reported on the incident reports. These physiological incidents may have involved either the aircrew, the passengers, or both. We also list the substances that caused the problems. Physiological responses ranged from nausea and lightheadedness to loss of consciousness. We discuss why flights involving a physiological incident may not have been aborted. The present military hazardous cargo incident reporting system is deficient in that there appears to be no requirement for reporting whether passengers were on board the incident aircraft, or whether passengers or aircrew suffered physiological responses to various toxic substances. PMID- 8357325 TI - Inflight medical aspects of a massive air evacuation. PMID- 8357326 TI - Inbuilt obsolescence in conventionally piloted advanced fighter aircraft. AB - If pilot and fighter plane capability to sustain accelerations in the 10 to 15 G range for many seconds or minutes provides an important tactical advantage, as some fighter pilots believe, currently used anti-G procedures, including the Combat Edge Technology (29), will provide only partial, questionably safe protection. Therefore, relative to preservation of maximal pilot effectiveness, current and future advanced fighters, if flown in seated positions, are physiologically outdated in respect to blackout and G-LOC prevention. Consequently, future victories in the air may come to the adversary first to discard conventional upright or partially supinated seats in favor of a biomedically advanced fighter, developed for flight in the fully horizontal, preferably prone, position. PMID- 8357327 TI - You're the flight surgeon. Flatus. PMID- 8357328 TI - Ventricular remodeling after myocardial infarction. Experimental and clinical studies. AB - Changes of ischemic myocardium following coronary occlusion, including active and passive functions, and adaptive changes of non-ischemic surviving myocardium have been summarized under the term "left ventricular remodeling" post myocardial infarction. An increase in left ventricular volume may be a consequence, and associated with an adverse prognosis. Although left ventricular dilatation may increase stroke volume and, thus, be compensatory at first, in about one-fifth of patients it ultimately results in progressive dysfunction and heart failure. Major determinants of this process are time, infarct size, infarct location, global left ventricular function assessed 4 days after infarction by radionuclide ejection fraction and right heart catheter (stroke volume), and morphology of the infarct-associated coronary artery. The surviving myocardium hypertrophies and may also dilate structurally. Depression of left ventricular ejection fraction chronically after the infarct is due to deterioration of wall motion of chamber segments initially classified normal by radionuclide analysis. Biochemical changes may also occur, including reduction of phosphocreatine, prolongation of time to peak Cai2+, and changes in myosin isoforms. Systemic or local humoral factors may be involved in these changes, however, clear evidence is still lacking. Perfusion of surviving myocardium may be altered under various conditions due to morphologic and functional changes of coronary vasculature. Successful prevention of heart failure and death by angiotensin converting enzyme inhibitors in asymptomatic patients with left ventricular dysfunction post myocardial infarction has supported the pathophysiologic concepts of remodeling. PMID- 8357329 TI - "Cardioprotection" by ACE-inhibitors in acute myocardial ischemia and infarction? AB - Coronary artery occlusion results in the acute activation of the renin angiotensin system and production of angiotensin II, a potent vasoconstrictor and positive inotropic agent. This has raised the possibility that angiotensin converting enzyme (ACE) inhibitors might be "cardioprotective" (that is, might attenuate myocardial injury, dysfunction and necrosis) in the setting of acute ischemia and infarction. Captopril, enalapril and ramipril have, in fact, been reported to acutely limit myocardial injury and necrosis in models of permanent coronary artery occlusion. The mechanisms responsible for this cardioprotection are complex, but include favorable alterations in myocardial oxygen supply/demand, and, in some instances, inhibition of bradykinin metabolism and/or increased prostaglandin synthesis. Other studies, however, have failed to document a reduction in infarct size with ACE inhibitor treatment. Results obtained in models of coronary occlusion/reperfusion have also been mixed. In models of brief transient ischemia not associated with necrosis, captopril and zofenopril have consistently been found to attenuate postischemic contractile dysfunction of the viable but "stunned" myocardium during the early hours following relief of ischemia. In contrast, there is no consensus on the effects of enalapril on the stunned myocardium: both positive and negative results have been obtained. Similar disparity has been reported in models of more prolonged ischemia/reperfusion resulting in subendocardial necrosis: some studies have reported myocardial salvage, while others have provided disturbing evidence of apparent exacerbation of myocardial necrosis with captopril and enalapril therapy. Thus, after a decade of investigative effort, the question of whether ACE inhibitors are "cardioprotective" in the setting of acute myocardial ischemia and infarction remains unresolved. Nonetheless, clinical protocols are in progress to assess the effects of early ACE inhibitor treatment in patients with acute myocardial infarction. PMID- 8357330 TI - Angiotensin, ACE-inhibitors and endothelial control of vasomotor tone. AB - The renin angiotensin system and endothelium-derived vasoactive substances are both important regulators of vascular tone. Recent evidence suggests that the two systems may be tightly interconnected and drugs interfering with one system may also affect the other. Beside the circulating renin angiotensin system, a vascular wall renin angiotensin system has been postulated and various components of it have been demonstrated in endothelial and vascular smooth muscle cells. Of particular importance is the angiotensin converting enzyme (ACE) which is identical to kininase II, which breaks down bradykinin into inactive components. Bradykinin is a potent activator of the L-arginine nitric oxide system (endothelium-derived relaxing factor). Hence, ACE-inhibitors not only deactivate the pressor system, but increase the local concentrations of bradykinin and thereby stimulate a potent endothelium-derived vasodilator system. Angiotensin II not only can activate vascular smooth muscle cells (where it causes contraction and proliferation), but also endothelial cells. In certain blood vessels, angiotensin II can stimulate prostacyclin production; in addition, angiotensin II activates endothelin messenger RNA in endothelial cells. This activation of the endothelin vasopressor system increases vascular tone and enhances the local vasoconstrictor responses (due to the amplifying effects of endothelin on noradrenaline- and serotonin-induced contractions). Although the acute effects of ACE-inhibitors in isolated blood vessels are restricted to inhibition of angiotensin I-induced contractions and augmentation of bradykinin-induced endothelium-dependent relaxations, chronic therapy with the drugs appears to enhance endothelium-dependent responses to several agonists, particularly in hypertensive animals. Hence, this mechanism of action of ACE-inhibitors may account for an important vascular protective effect of the drugs. Thus, in summary, the renin angiotensin system and endothelium-derived vasoactive substances are tightly interconnected. This may be important under physiological and pathophysiological conditions, and is of importance for the action of currently available cardiovascular drugs, in particular, ACE-inhibitors. PMID- 8357331 TI - Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview. AB - There are multiple mechanisms whereby ACE inhibitors could be beneficial during myocardial ischemia and reperfusion, including: i) reduced formation of angiotensin II, ii) decreased metabolism of bradykinin, iii) antioxidant activity, and iv) possibly other unknown mechanisms. Reduced formation of angiotensin II should be beneficial because this peptide exerts several actions that are potentially detrimental to the ischemic/reperfused myocardium, including vasoconstriction, increased release of norepinephrine, stimulation of phospholipase C and/or A2, and increased afterload with an attendant increase in oxygen demands. Reduced metabolism of bradykinin could be beneficial by increasing myocardial glucose uptake, by causing vasodilation, and by stimulating production of endothelium-derived relaxing factor and prostacyclin. Although earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs scavenge hydroxyl radical and hypochlorous acid with no effect on superoxide anion. Studies in isolated hearts have demonstrated that ACE inhibitors attenuate the metabolic, arrhythmic, and contractile dearrangements associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin and/or increased synthesis of prostacyclin. Studies in models of myocardial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile function after a single brief ischemic episode. No data are available regarding the effect of these drugs on myocardial stunning after a prolonged, partly reversible episode, after multiple consecutive brief ischemic episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involve an antioxidant action (in the case of thiol containing molecules) or potentiation of prostaglandins (in the case of non-thiol containing molecules). What is clear is that the enhanced recovery of function effected by these drugs is not due to hemodynamic effects, inhibition of the converting enzyme per se, or an "antischemic" action (since the drugs were effective when given at the time of reperfusion). The effects of ACE inhibitors on myocardial infarct size remain controversial. Further studies will be necessary to conclusively establish whether ACE inhibitors can protect against the detrimental effects of myocardial ischemia and reperfusion. Nevertheless, the evidence provided thus far is encouraging and warrants an in-depth assessment of the role of these drugs in attenuating myocardial ischemia/reperfusion injury. PMID- 8357332 TI - Angiotensin-converting enzyme inhibitor in a human model of restenosis. MERCATOR ("Multicenter European Research Trial with Cilazapril after Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis") Study Group. PMID- 8357333 TI - Pathophysiology of heart failure and the renin-angiotensin-system. AB - For more than a decade, the inhibition of the renin-angiotensin system in heart failure has been regarded as pure vasodilator therapy. Consequently, the role of the renin-angiotension system has been seen as contributing to hemodynamic overload by vasoconstriction and volume retention. Meanwhile, clinical experience was indicated that important additional aspects of ACE-inhibition in heart failure are attenuation of the enhanced neuroendocrine activity and reversal or prevention of inappropriate trophic reactions of the overloaded myocardium. In overloaded hearts there is enhanced intracardiac formation of angiotensin due to enhanced expression of angiotensinogen and ACE, and due to accumulation of circulating, nephrogenic active renin. In human hearts, a mast-cell-derived chymase, which is not blocked by ACE-inhibition, contributes to intracardiac angiotensin formation. The enhanced intracardiac angiotensin-II formation in overloaded hearts is involved in coronary constriction, impairment of diastolic relaxation, myocyte enlargement and interstitial fibrosis, which aggravate the diastolic impairment. The major problem in overloaded, hypertrophied cardiocytes is the dedifferentiation with instabilization of Ca(++)-homeostasis due to an altered program of gene expression. Dedifferentiated cardiocytes have a reduced expression of sarcoplasmic reticulum Ca(++)-ATPase and an enhanced expression of the sarcolemmal Na+/Ca(++)-exchanger, resulting in an attenuation of active diastole (Ca(++)-reaccumulation into the sarcoplasmic reticulum), a depressed force-frequency relation, and an enhanced susceptibility for fatal arrhythmias. Furthermore, an enhanced local renin-angiotensin system in distensible coronary and systemic arteries seems to contribute to a reduced releasability of endothelium-derived relaxing factor, probably by reducing bradykinin availability. This modulation of endothelial function appears to contribute to the localization and progression of atheroma development in presence of risks factors for atherosclerosis. PMID- 8357334 TI - Angiotensin-converting enzyme inhibitors in the treatment of clinical heart failure. AB - During the last decade, angiotensin-converting enzyme inhibitors (ACE-I) have become cornerstones in the treatment of clinical congestive heart failure. There is convincing evidence that they improve survival and that, in this respect, they are superior to ordinary vasodilators. ACE-I administration also improves New York Heart Association functional class and the left-ventricular function, but their long-term effects on exercise tolerance and quality of life appear modest. During prolonged administration to patients with ischemic left-ventricular dysfunction, ACE-I also significantly reduce the incidence of new ischemic events (myocardial infarction, unstable angina). PMID- 8357335 TI - ACE-inhibitors in coronary artery disease? AB - Angiotensin converting enzyme (ACE)-inhibitors are established in the treatment of arterial hypertension and heart failure. In recent years ACE-inhibitors have also been used in the treatment of patients with coronary artery disease (CAD), since from experimental data an antiischemic action of these agents is suggested. Antiischemic effects of ACE-inhibitors may be exerted through a reduction of myocardial oxygen demand, by a reduction of angiotensin-mediated coronary vasoconstriction, by an interaction with bradykinin and the prostaglandin system, by a modulation of endothelial control of vascular tone, and by an interaction with the sympathetic nervous system. However, clinical findings on potential beneficial effects of ACE-inhibitors in patients with CAD are inconsistent and controversial. While in hypertensive patients with CAD ACE-inhibitors generally seem to attenuate myocardial ischemia at rest and during exercise, a significant fraction of about 30% of normotensive patients with CAD does not benefit or even deteriorates. Lowering of coronary perfusion pressure and alteration of transmural blood flow distribution may be responsible for this. In patients with left ventricular dysfunction (SOLVD) or congestive heart failure (CONSENSUS, SOLVD) ACE-inhibitors have been proven to prevent progressive deterioration in left ventricular function and to reduce mortality. In patients with asymptomatic left ventricular dysfunction after myocardial infarction (SAVE), long-term administration of captropril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. Therefore, from a prognostic viewpoint patients with CAD and left ventricular dysfunction or congestive heart failure should be treated with ACE-inhibitors, although the clinical use of ACE-inhibitors in patients with ongoing angina pectoris may be limited by an aggravation of angina, presumably due to critically lowering coronary perfusion pressure. Finally, ACE-inhibitors failed to prevent restenosis after successful PTCA. In conclusion, from a prognostic viewpoint patients with CAD and congestive heart failure or left ventricular dysfunction should be treated with ACE-inhibitors. In hypertensive patients ACE-inhibitors generally seem to attenuate myocardial ischemia. In normotensive patients with CAD and angina pectoris but without left ventricular dysfunction ACE-inhibitors cannot generally be recommended at present, unless the patients, which may have benefit from ACE-inhibitor treatment can be better defined. PMID- 8357336 TI - Molecular mechanisms of cardiac gene expression. AB - Although the physiological properties of the myocardium and their dynamic character have been the focus of intense research during the past three decades, the biochemical and molecular correlates underlying cardiac development and performance have, until recently, remained poorly understood. The development of modern cellular and molecular biology has provided the necessary tools to undertake the study of the mechanisms involved in cardiac development and to understand the basis for important clinical and experimental problems in cardiovascular physiology. Most of the gene encoding contractile proteins have been cloned and characterized. The availability of molecular probes and the ability to introduce genes into individual cell types and tissues of living animals, are the most important breakthroughs of molecular and cell biology. This permits not only to analyze basic mechanisms of gene expression but has also significant practical applications for gene therapy. It is now possible to analyze the role of different regulatory gene sequences and identify their corresponding trans-active factors. In addition, direct gene injection makes it possible to study gene expression in a natural context, under conditions that are physiologically relevant and controllable. PMID- 8357337 TI - Myocardial perfusion dependent and independent mechanisms of regional myocardial dysfunction in hypertrophy. AB - Reduced coronary reserve is one of the hallmarks of ventricular hypertrophy. Although this reduced coronary reserve may not affect baseline left ventricular (LV) function, it could be of greater importance during periods of stress such as occurs during exercise where increased metabolic demands induced by the stress may not be fully met by increases in coronary blood flow. The impaired subendocardial coronary reserve is caused not only by the hypertrophy but also by the hemodynamic changes, e.g., the LV subendocardial wall stress, which increases markedly upon exercise. In the severely hypertrophied heart during exercise there is impaired subendocardial wall function even after 10 beats, i.e., the first 3 s of exercise, at a time when LV pressures and stresses had not increased, and subendocardial perfusion was still preserved. During more severe exercise, subendocardial dysfunction persisted and was associated with reduced subendocardial perfusion. After beta-adrenergic receptor blockade with propanolol, the most intense level of exercise was associated with lesser increase in systolic and diastolic LV wall stresses, heart rate, and LV dP/dt, and the endo/epi blood flow ratio, an index of adequacy of subendocardial perfusion, was no longer reduced below unity, and there were no decreases in subendocardial wall thickening. Thus, the subendocardial dysfunction occurred rapidly, before alterations in LV systolic or diastolic wall stress or an alteration in the endo/epi blood flow ratio. However, the subendocardial hypoperfusion and depression in subendocardial wall thickening observed during more severe exercise in dogs with LV hypertrophy was prevented by pretreatment with beta-adrenergic receptor blockade. Therefore, myocardial perfusion dependent and independent mechanisms mediate regional myocardial dysfunction during exercise in the hypertrophied heart. PMID- 8357338 TI - ACE-inhibitors and coronary microcirculation. AB - Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris-symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine to what extent under clinical conditions coronary flow reserve can be improved, in hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (Dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with the ACE-inhibitor enalapril (10-20 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, the coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a decrease in LV muscle mass by about 8%, coronary reserve was improved after enalapril by 48%. It is likely that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities at the level of the coronary microcirculation. Consequently, it seems that reparation of hypertensive remodeling of the coronary microcirculation can be induced by ACE-inhibitor therapy. PMID- 8357339 TI - Genetic control of fungal differentiation: the three sporulation pathways of Neurospora crassa. AB - Sporulation in the mold Neurospora crassa can proceed along three very different pathways, leading to the production of three types of spores. Two asexual sporulation pathways that lead to the formation of macroconidia and microconidia involve budding from hyphae by two different mechanisms. A much more complex sexual reproductive pathway involves the formation of a fruiting body called a perithecium, in which meiosis takes place and ascospores are formed in sac-like cells called asci. Numerous mutations exist that affect these developmental pathways and genes have been isolated that are expressed preferentially during sporulation. The Neurospora sporulation pathways offer a simple system with which to study mechanisms and regulation of development that are usually obscured by complex cell-cell interactions involved in animal and plant development. PMID- 8357340 TI - Integrins hold Drosophila together. AB - The Drosophila position-specific (PS) integrins are members of the integrin family of cell surface receptors and are thought to be receptors for extracellular matrix components. Each PS integrin consists of an alpha subunit, alpha PS1 or alpha PS2, and a beta PS subunit. Mutations in the beta PS subunit and the alpha PS2 subunit have been characterised and reveal that the PS integrins have an essential role in the adhesion of different cell layers to each other. The PS integrins are especially required for the function of the cell matrix-cell junctions, where the muscles attach to the epidermis and where one surface of the developing wing adheres to the other. These junctions are similar to vertebrate focal adhesions and hemidesmosomes, which also contain integrins. Integrin-mediated cell to cell adhesion via the extracellular matrix provides a way for tissues to adhere to each other without intermingling of their cells. PMID- 8357341 TI - Dynamic aspects of adhesion receptor function--integrins both twist and shout. AB - The recognition of extracellular molecules by cell surface receptors is the principal mechanism used by cells to sense their environment. Consequently, signals transduced as a result of these interactions make a major contribution to the regulation of cellular phenotype. Historically, particular emphasis has been placed on elucidating the intracellular consequences of growth factor and cytokine binding to cells. In addition to these interactions, however, cells are usually in intimate contact with a further source of complex structural and functional information, namely immobilised extracellular matrix and/or cell surface adhesion proteins. A key question in recent years has been whether cells use the myriad of adhesion protein-receptor interactions purely for structural and migratory function, or whether these interactions also make a more varied contribution to cell phenotype. Here we review dynamic aspects of the function of one major class of adhesion receptor, the integrins. In particular, we focus on the evidence for shape changes in integrin molecules, the mechanisms responsible for regulating ligand binding, and the signals transduced following integrin occupancy. PMID- 8357342 TI - Meiosis, mitosis and microtubule motors. AB - A framework for understanding the complex movements of mitosis and meiosis has been provided by the recent discovery of microtubule motor proteins, required for the proper distribution of chromosomes or the structural integrity of the mitotic or meiotic spindle. Although overall features of mitosis and meiosis are often assumed to be similar in mechanism, it is now clear that they differ in several important aspects. These include spindle structure and assembly, and timing of chromosome segregation to opposite poles. Here we review progress in the functional characterization of several newly identified microtubule motor proteins, emphasizing their possible roles in spindle structure and function. PMID- 8357343 TI - The role of DNA repeats and associated secondary structures in genomic instability and neoplasia. AB - Tumour-associated genetic changes frequently involve DNA translocation or deletion. Many of these events will have arisen from initial genomic damage, induced by either the activity of endogenous metabolic processes or from exposure to environmental genotoxic agents. Although initial genomic damage will have been widely distributed, tumorigenic events are confined to certain DNA target sites. Furthermore, within these target sites there appear to be regions of preferential DNA rearrangement, and examination of these sites implies that the location and extent of such rearrangement may be influenced by DNA primary and secondary structure rather than simply by the point of damage. We selectively review evidence relating to DNA structures that may predispose certain regions of the genome to damage-induced rearrangement, and discuss the possible role of interstitial, inverted telomere-like sequence arrays in promoting chromosomal events of a type known to be associated with some human and animal tumours. PMID- 8357344 TI - Dystrophin as a mechanochemical transducer in skeletal muscle. AB - This review is primarily concerned with two key issues in research on dystrophin: (1) how the protein interacts with the plasma membrane of skeletal muscle fibres and (2) how an absence of dystrophin gives rise to Duchenne muscular dystrophy. In relation to the first point, we suggest that the post-translational acylation of dystrophin may contribute to its interaction with the plasma membrane. Regarding the second point, it is generally considered that an absence of dystrophin makes the plasma membrane susceptible to damage by contraction/relaxation cycles. In this connection, we propose that the progressive nature of Duchenne dystrophy, and the phenotypic characteristics of mdx mice, are more consistent with dystrophin functioning as a mechanical transducer that transmits growth stimuli from the enlarging skeleton to the muscle. On the basis of this hypothesis, dystrophin-deficient muscles would be unable to grow at the same rate as the skeleton. PMID- 8357345 TI - Werner syndrome and biological ageing: a molecular genetic hypothesis. AB - Werner syndrome (WS) is an inherited disorder that produces somatic stunting, premature ageing and early onset of degenerative and neoplastic diseases. Cultured fibroblasts derived from subjects with WS are found to undergo premature replicative senescence and thus provide a cellular model system to study the disorder. Recently, several overexpressed gene sequences isolated from a WS fibroblast cDNA library have been shown to possess the capacity to inhibit DNA synthesis and disrupt many normal biochemical processes. Because a similar constellation of genes is overexpressed in WS and senescent normal fibroblasts, these data suggest the existence of a common molecular genetic pathway for replicative senescence in both types of cell. We propose that the primary defect in WS is a mutation in a gene for a trans-acting repressor protein that reduces its binding affinity for shared regulatory regions of several genes, including those that encode inhibitors of DNA synthesis (IDS). The mutant WS repressor triggers a sequence of premature expression of IDS and other genes, with resulting inhibition of DNA synthesis and early cellular senescence, events which occur much later in normal cells. PMID- 8357346 TI - Biological, physical, and electrical parameters for in vitro studies with ELF magnetic and electric fields: a primer. AB - This paper presents material which is intended to assist researchers in identifying and controlling a range of biological, electrical, and other physical parameters that can affect the outcome of in vitro studies with extremely low frequency (ELF) magnetic and electric fields. Brief descriptions of power line magnetic and electric fields are provided and methods for the generation of 60 Hz as well as other ELF fields in the laboratory are surveyed. Methods for calculating and measuring exposure parameters in culture medium are also described. Relating in vitro and internal in vivo exposure conditions across different animal species is discussed to aid researchers in selecting levels of field exposure. The text is purposely elementary, and sometimes brief, with references provided to aid the interested reader in obtaining a fuller understanding of the many topics. Because the range of experimental parameters that can influence the outcome of in vitro studies with ELF fields is so broad, a multidisciplinary approach is normally required to carry out the research. PMID- 8357347 TI - Immunodetection of human atherosclerotic plaque with 125I-labeled monoclonal antifibrin antibodies. AB - To test the affinity of a new F(ab')2 monoclonal antibody (TRF1) against human fragment D dimer of cross-linked fibrin for atherosclerotic plaques free of detectable thrombi, 6 atherosclerotic segments of carotid and femoral artery, and as a control 5 segments of atherosclerosis-free internal mammary artery, were drawn from 11 male patients undergoing bypass surgery. All segments were carefully washed in order to remove possible endoluminal thrombi, and cut to obtain pairs of intimal fragments of similar weight, containing either plaques (n = 16), or fatty streaks (n = 12), or normal endothelium (n = 20). Each fragment underwent a direct binding test to TRF1, or to a non-specific antibody, both labeled with 125I. The activity in each fragment was measured after 3 h of incubation at 37 degrees C, and after washing the fragments every hour for 3 h. TRF1 binding (as percentage of initial activity) was significantly higher (P < 0.001) in atherosclerotic than in normal fragments (26% +/- 11.5%, vs. 9.2% +/- 3.9% in fatty streaks, and 1.9% +/- 0.6% in normal endothelium), and indirect immunofluorescence confirmed TRF1 uptake within the plaque wall. By contrast, the non-specific antibody did not show any significant binding. These preliminary results demonstrate the high specific affinity of TRF1 for atherosclerotic plaques, probably due to the hemorheologic phenomena that activate platelets and provoke the formation of fragment D dimers of cross-linked fibrin on the plaque surface. PMID- 8357348 TI - Ramipril prevents impaired endothelium-dependent relaxation in arteries from rabbits fed an atherogenic diet. AB - Endothelium-dependent relaxation in arteries is attenuated in clinical and experimental atherosclerosis. This study investigates the endothelial preservation properties of the angiotensin converting enzyme inhibitor, ramipril, by assessing its ability to restore endothelium-dependent responsiveness in blood vessels from rabbits fed an atherogenic diet (0.25% cholesterol; 3% coconut oil; 12 weeks). Seven rabbits fed the atherogenic diet received ramipril (3 mg/kg mixed into their food daily) and 6 rabbits were maintained on the atherogenic diet alone. Control rabbits (n = 6) were fed a standard diet and did not receive ramipril. At the end of the dietary intervention, the rabbits were killed and blood was collected for measurement of the lipid profile. The thoracic aorta was isolated and half was frozen for pathologic review while the other half was cut into rings and placed in a muscle bath for measurement of isometric force development. Dose response curves to phenylephrine (10(-9) to 10(-5) M) and angiotensin II (10(-10) to 3 x 10(-7) M) were completed. There was a minimal decrease in responsiveness to phenylephrine in vessels from rabbits eating the atherogenic diet compared with controls and no significant differences in the response to angiotensin II for any of the vessels. Following contraction by phenylephrine, acetylcholine (10(-9) to 10(-5) M) and nitroglycerin (10(-10) to 10(-5) M) dose response curves were completed. Relaxation to acetylcholine in aortic rings from control rabbits was observed, although in arteries from atherogenic rabbits relaxation was attenuated. This effect was prevented in the atherogenic rabbits fed ramipril. Responsiveness to the endothelium-independent vasodilator, nitroglycerin, was similar in arteries from the three rabbit groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357349 TI - Probucol inhibits mononuclear cell adhesion to vascular endothelium in the cholesterol-fed rabbit. AB - Mononuclear cells, isolated from the blood of hyperlipidaemic patients, are hyper reactive and possess an increased propensity to adhere to vascular endothelial cells. Hyperlipidaemia is also associated with a dysfunctional endothelium, to which mononuclear cells stick with greater avidity. In order to assess the importance of lipid peroxidation and free-radical generation in these processes, we have investigated the effects of probucol on mononuclear cell adhesion to vascular endothelial cells in vivo and in vitro in the cholesterol-fed rabbit. New Zealand White rabbits were fed either: (i) control chow (n = 15), (ii) 2% cholesterol (n = 11), or (iii) 2% cholesterol with 1% probucol (n = 11). Mononuclear cell adherence to endothelium in the common carotid artery was assessed 5 weeks after the start of the experimental diet using the Hoechst 33342 staining technique. The 2% cholesterol diet caused a more than 6-fold increase in mean mononuclear cell adherence (P < 0.001). Concurrent probucol therapy abrogated the effects of cholesterol feeding, and in animals in this group, in vivo mononuclear cell adherence did not differ significantly from control animals. In vivo mononuclear cell adherence was directly related to serum cholesterol levels (r = 0.68, P < 0.0001) and inversely related to serum probucol concentrations (r = -0.63, P < 0.002). Concurrent probucol therapy also reduced the in vitro binding of mononuclear cells, isolated from hypercholesterolaemic animals, to endothelial cell monolayers (P < 0.01). These data suggest that the increased binding of mononuclear cells to vascular endothelium of cholesterol-fed rabbits may be a free radical mediated process that is inhibited by antioxidants. PMID- 8357350 TI - Lp(a) levels and antiestrogen antibodies in women with and without thrombosis in the course of oral contraception. AB - Several reports have shown that lipoprotein(a) is associated with ischemic diseases. Two characteristics might explain this association. Firstly, Lp(a) is an LDL-like lipoprotein which may be implicated in the atherosclerotic process and secondly, Lp(a) possesses an additional apolipoprotein(a) whose structure is close to that of plasminogen and might confer to the molecule prothrombotic properties. It seemed of interest to see whether Lp(a) was a risk factor in oral contraceptive users with thrombotic complications, a group of young women with presumably little or no atherosclerosis. Three groups of women were compared: 25 of them served as controls and did not use oral contraceptives (OC) (group 1); 25 women were healthy current users of OC (group 2); 35 women suffered thrombotic complications in the course of OC (group 3). Mean levels of Lp(a), estimated by RID, were not found to be significantly different in the 3 groups: 19 +/- 18, 20 +/- 23 and 16 +/- 22 mg/dl, respectively. Levels above 30 mg/dl were similarly distributed. Among the other risk factors studied, antiestrogen antibodies were absent in group 1, present in 24% of group 2 and 71.4% of group 3 (P < 0.01). Serum cholesterol levels were similar in the 3 groups: 209 +/- 33, 220 +/- 41, 213 +/- 45 mg/dl respectively. Mean serum triglyceride levels were higher in group 2 than in group 1 (61 +/- 18 and 83 +/- 32, P < 0.01), and higher in group 3 than in group 2 (116 +/- 66 and 83 +/- 32, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357351 TI - Effect of linoleic acid hydroperoxide on production of matrix metalloproteinases by human aortic endothelial and smooth muscle cells. AB - The effect of linoleic acid hydroperoxide on the production of proforms of matrix metalloproteinase-1, -2, and -3 (proMMP-1, -2, and -3) in cultured human arterial endothelial and smooth muscle cells was investigated. Upon cultivation of the endothelial cells in the absence of the hydroperoxide, only proMMP-1 was detected, and its amount was increased by cultivation with the hydroperoxide. In the cultures of the intimal smooth muscle cells in the absence of the hydroperoxide, a large amount of proMMP-2 and small amounts of proMMP-1 and -3 were detected, and the hydroperoxide treatment increased remarkably the amounts of proMMP-1 and -3, but rather decreased the amount of proMMP-2. In the cultures of the medial smooth muscle cells, the same tendency was observed. However, the amounts of these proenzymes found in the intimal smooth muscle cells exceeded those found in the medial smooth muscle cells, both in the absence and in the presence of the hydroperoxide. Possible involvement of these phenomena in atherogenesis was discussed. PMID- 8357352 TI - Ultrastructural studies on the phenotypic modulation of human intimal smooth muscle cells. AB - The present study was carried out to clarify the mechanism of intimal thickening at the ostia of celiac and superior mesenteric arteries. The cell components involved in the process were analyzed under electron microscope. Autopsy samples from cases without significant atherosclerotic diseases were examined and the percentages of smooth muscle cells in either synthetic or contractile state, macrophages, and foam cells in the intima of mesenteric and celiac arteries were calculated. Smooth muscle cells in the synthetic state were predominant in the proximal region and those in the contractile state were predominant in the distal region. Few macrophages were present in both regions. The intima in the proximal and distal regions of celiac arteries in autopsy samples was further divided into three layers and the percentages of various smooth muscle cell phenotypes in each layer were calculated and compared in patients at different ages. In the proximal region, the phenotype of the smooth muscle cells changed from the synthetic to the contractile state from the deeper to the superficial layers with the advance of age. In the distal region, the contractile state was dominant regardless of the age. These results suggest that the phenotypic modulation of human intimal smooth muscle cells is reversible dedifferentiation-redifferentiation process; this phenomenon plays an important role in the initiation of atherosclerosis. PMID- 8357353 TI - Targeting of experimentally induced atherosclerotic lesions by liposome-delivered Zn(II)-phthalocyanine. AB - Zn(II)-Phthalocyanine (Zn-Pc) is an exogenously administrable dye which is accumulated by tumors and other rapidly proliferating tissues. This property could be used for visualising atherosclerotic plaques. In order to define the feasibility and the optimal conditions for in vivo labelling of atheroma, we evaluated the ability of Zn-PC to be accumulated by experimentally induced atherosclerotic lesions in rabbits. We also performed pharmacokinetic investigations to assess photosensitizer delivery system, difference in phthalocyanine concentration between normal and atherosclerotic vessels, and the time interval after administration, which yields a large difference between normal and diseased vessels. We observed a preferential accumulation of Zn-Pc by atherosclerotic lesions which accumulated about a tenfold larger amount of photosensitizer, and the retention of significant amounts for prolonged periods. Zn-Pc can be considered as a potentially useful fluorescence marker for atheroma. The feasibility of photodiagnosis and phototherapy of atheroma deserves further investigation. PMID- 8357354 TI - Changes in antioxidant enzymes activities, aggregability and malonyldialdehyde concentration in blood platelets from patients with coronary heart disease. AB - In 41 patients with coronary heart disease (CHD) the concentrations of total blood platelet malonyldialdehyde (MDA: 2.11 +/- 0.25 nmol/10(9) platelets) and MDA corresponding to thromboxane A2 (TXA2 0.84 +/- 0.13 nmol/10(9) platelets) were increased in comparison with values in blood platelets of healthy subjects (1.19 +/- 0.09 and 0.71 +/- 0.05 nmol/10(9) platelets), respectively. The increased aggregability with ADP and thrombin of patient platelets was also observed. In relation to the blood platelets of healthy subjects, the antioxidant enzymes activities of patient blood platelets were significantly (P < 0.001) decreased. Platelet glutathione peroxidase (GSH-Px) activity of the patients (11.3 +/- 0.85 U/g protein) was significantly lower than controls (18.3 +/- 1.12 U/g protein). In patients with CHD the activities of the other antioxidative platelet enzymes: catalase (Cat, 7.37 +/- 1.38 U/g protein) and superoxide dismutase (SOD, 1529.4 +/- 167 U/g protein) were also significantly decreased in comparison with values for healthy subjects (Cat: 9.06 +/- 1.30 U/g protein and SOD: 1987 +/- 230 U/g protein, respectively). It is suggested that antioxidative defense in blood platelets may affect the haemostatic processes and lipid peroxidation in patients with CHD. PMID- 8357355 TI - Effects of a high-fat, sucrose diet on serum insulin and related atherosclerotic risk factors in rats. AB - Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are all risk factors for atherosclerosis. The clustering of these risk factors in the same individual greatly increases the risk for atherosclerosis and has been termed 'Syndrome X' or 'The Deadly Quartet' The purpose of the present study was to investigate the effects of diet on these risk factors in inbred, female Fischer 344 rats. Animals were raised on ad lib diets consisting of high-fat, sucrose (HFS) or low-fat, complex-carbohydrate (LFCC). After 2 years, the HFS rats were obese (38% +/- 1% vs. 15% +/- 1% body fat), hypertensive (140 +/- 3 vs. 123 +/- 3 mmHg), hyperinsulinemic (439 +/- 118 vs. 98 +/- 10 pmol/l), and hypertriglyceridemic (1.1 +/- 0.2 vs. 0.4 +/- 0.07 mmol/l). The HFS rats also exhibited enhanced clotting and impaired fibrinolytic response to streptokinase. All these differences between the two groups were statistically significant (P < 0.05). Insulin was significantly correlated with body weight (r = 0.71), triglycerides (r = 0.48), and systolic blood pressure (r = 0.70). Total cholesterol was slightly, but not significantly higher, in the HFS group (2.8 +/- 0.3 vs 2.2 +/- 0.1 mmol/l) while HDL-cholesterol was unchanged. These results show that many risk factors for atherosclerosis can be induced in inbred rats by feeding a HFS diet. Aggregation of risk factors was found in the HFS group but not in the LFCC group. In fact, most of the rats on the LFCC diet developed no risk factors after 2 years, indicating that the development of risk factors is not an aging phenomenon. PMID- 8357356 TI - Monocyte/macrophage accumulation and smooth muscle cell phenotypes in early atherosclerotic lesions of human aorta. AB - In a search for early atherosclerotic lesions, we have investigated grossly normal areas of human thoracic aortas taken at autopsy from 40 trauma victims aged from 3 to 40 years. Two areas of aorta were compared: lesion predisposed to atherosclerosis (LP) area localized on the dorsal aspect of the vessel along the row of intercostal branching sites, and lesion resistant (LR) area located on the ventral aspect of the vessel. Accumulation of apolipoprotein B (apo B) was found in LP aortic area of each child older than 6 years. Similar retention of apo B in LR area appeared only in aortas of teenagers. The apo B staining increased with age in both areas tested but was usually of a greater extent in LP area than in LR area. Typical smooth muscle cells (SMCs) and a few monocytes/macrophages (Mn/Mph) were revealed in the intimal layer of all aortas examined. The number of Mn/Mph dramatically increased in LP areas of individuals over 17 years. Quantitative study of double stained sections has shown a 2- to 6-fold enhanced number of Mn/Mph in LP area compared with LR aortic area of 10 men over 21 years. Focal infiltration of Mn/Mph in aortas of young adults occurred without endothelial denudation. In addition, some intimal SMCs in LP area of 12 aortas out of 29 expressed desmin and contained well-developed endoplasmic reticulum, while such cells were seldom detected in LP area of the vessels. Thus, focal accumulation of apo B with subsequent Mn/Mph infiltration and SMC phenotypic modulation in LP aortic area of young adults may be causally involved in fatty streak and atherosclerotic plaque formation. PMID- 8357357 TI - Westernized food habits and concentrations of serum lipids in the Japanese. AB - To investigate the association of westernized food habits and concentrations of serum lipids in the Japanese, we studied 1200 healthy Japanese living in Hiroshima prefecture and 1483 ethnic Japanese from Hiroshima prefecture living in the Hawaii Islands and Los Angeles. The nutritional assessments were made by the same dietitians. No major difference was observed in the total energy intake between the Japanese and the Japanese-Americans in both males and females. However, the intake of animal fat and simple carbohydrates (especially fructose) were markedly greater, and that of complex carbohydrates lower, in the Japanese Americans compared with the Japanese. The mean serum cholesterol (CH), LDL-CH and serum triglyceride (TG) levels were significantly higher in the Japanese Americans in both sexes. The mean HDL-CH concentration was similar between the two groups in males, but it was approximately 7 mg/dl higher in Japanese-American females. Using the 75 percentile values of CH and TG in the Japanese in Hiroshima, the frequency of WHO types IIa and IIb hyperlipidemia was about twice as high in the Japanese-Americans. These results suggest that westernized food habits in the Japanese include qualitative changes in animal fat, simple carbohydrate and complex carbohydrate diet rather than an increase in the total energy intake. These changes are associated with marked increases in the concentrations of serum CH and TG and increased prevalence of types IIa and IIb hyperlipidemia. PMID- 8357358 TI - Seasonal variation in high density lipoprotein cholesterol. AB - We investigated the seasonal variation in high density lipoprotein cholesterol (HDL) in 142 dyslipidemic (non-HDL-cholesterol > or = 5.2 mmol/l) middle-aged men in the placebo group of the Helsinki Heart Study over the 5-year trial period. A seasonal pattern was found in HDL fluctuation, with a 4.5% drop during mid-winter (5-year mean 1.192 +/- 0.265 mmol/l) compared with a stable level (5-year mean 1.248 +/- 0.281 mmol/l) during the rest of the year (P < 0.001). A less pronounced seasonal variation in HDL was observed in 85 subjects receiving gemfibrozil. Although affecting pretrial HDL level in cross-sectional analyses, age, alcohol consumption, dietary adherence, physical activity and serum triglycerides had no influence on the seasonality of HDL variation. Smoking had a slight attenuating effect on the variation pattern. Pretrial HDL was influenced by relative weight, but there was also an inverse relationship between HDL and body weight variations, i.e. the annual drop in HDL coincided with the annual peak in body weight. However, seasonal HDL variation was not directly reflected in the annual variation in CHD incidence. PMID- 8357359 TI - Inhaled nitric oxide for the adult respiratory distress syndrome. AB - BACKGROUND: The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood. We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions, thereby reducing pulmonary hypertension and improving gas exchange. METHODS: Nine of 10 consecutive patients with severe adult respiratory distress syndrome inhaled nitric oxide in two concentrations for 40 minutes each. Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin. Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million (ppm) for 3 to 53 days. RESULTS: Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean (+/- SE) pulmonary-artery pressure from 37 +/- 3 mm Hg to 30 +/- 2 mm Hg (P = 0.008) and decreased intrapulmonary shunting from 36 +/- 5 percent to 31 +/- 5 percent (P = 0.028). The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2), an index of the efficiency of arterial oxygenation, increased during nitric oxide administration from 152 +/- 15 mm Hg to 199 +/- 23 mm Hg (P = 0.008), although the mean arterial pressure and cardiac output were unchanged. Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure. Continuous nitric oxide inhalation consistently lowered the pulmonary-artery pressure and augmented the PaO2/FiO2 for 3 to 53 days. CONCLUSIONS: Inhalation of nitric oxide by patients with severe adult respiratory distress syndrome reduces the pulmonary-artery pressure and increases arterial oxygenation by improving the matching of ventilation with perfusion, without producing systemic vasodilation. Randomized, blinded trials will be required to determine whether inhaled nitric oxide will improve outcome. PMID- 8357360 TI - Effects of walnuts on serum lipid levels and blood pressure in normal men. AB - BACKGROUND: In a recent six-year follow-up study, we found that frequent consumption of nuts was associated with a reduced risk of ischemic heart disease. To explore possible explanations for this finding, we studied the effects of nut consumption on serum lipids and blood pressure. METHODS: We randomly placed 18 healthy men on two mixed natural diets, each diet to be followed for four weeks. Both diets conformed to the National Cholesterol Education Program Step 1 diet and contained identical foods and macronutrients, except that 20 percent of the calories of one diet (the walnut diet) were derived from walnuts (offset by lesser amounts of fatty foods, meat, and visible fat [oils, margarine, and butter]). RESULTS: With the reference diet, the mean (+/- SD) serum values for total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were, respectively, 182 +/- 23, 112 +/- 16, and 47 +/- 11 mg per deciliter (4.71 +/- 0.59, 2.90 +/- 0.41, and 1.22 +/- 0.28 mmol per liter). With the walnut diet, the mean total cholesterol level was 22.4 mg per deciliter (0.58 mmol per liter) lower than the mean level with the reference diet (95 percent confidence interval, 28 to 17 mg per deciliter [0.72 to 0.44 mmol per liter]); the LDL and HDL cholesterol levels were, respectively, 18.2 mg per deciliter (0.47 mmol per liter) (P < 0.001) and 2.3 mg per deciliter (0.06 mmol per liter) (P = 0.01) lower. These lower values represented reductions of 12.4, 16.3, and 4.9 percent in the levels of total, LDL, and HDL cholesterol, respectively. The ratio of LDL cholesterol to HDL cholesterol was also lowered (P < 0.001) by the walnut diet. Mean blood-pressure values did not change during either dietary period. CONCLUSIONS: Incorporating moderate quantities of walnuts into the recommended cholesterol-lowering diet while maintaining the intake of total dietary fat and calories decreases serum levels of total cholesterol and favorably modifies the lipoprotein profile in normal men. The long-term effects of walnut consumption and the extension of this finding to other population groups deserve further study. PMID- 8357361 TI - Anaphylactoid reaction following local anaesthesia for epidural block. AB - A potentially serious complication of epidural bupivacaine used for a repeat, elective Caesarean section is presented. The main features of this reaction were erythema, itching, generalised and pulmonary oedema. In addition, pulmonary oedema was subsequently noted in the baby. An immunological hypersensitivity to bupivacaine or lignocaine is the likely cause. PMID- 8357362 TI - Activated glutaraldehyde. PMID- 8357363 TI - [Children with minimal brain dysfunction in the family]. PMID- 8357364 TI - Indications for hysterectomy. PMID- 8357365 TI - The new face of AIDS. PMID- 8357367 TI - Trends in prenatal diagnosis of Down's syndrome. PMID- 8357366 TI - Condoms and contraceptives in junior high and high school clinics. What do you think? PMID- 8357368 TI - Early soft-tissue complications after distal radius fractures. PMID- 8357369 TI - [The international in nursing. Ethics and foreign cultures]. PMID- 8357370 TI - Weighting in the dark: resource allocation in the new NHS. AB - National allocation of resources to regional health authorities and by them to districts is now determined by a weighted capitation formula. The national formula was derived from regression analysis, with hospital utilisation as an index of need for health care--a method which has fundamental limitations. This paper argues that the search for an empirically based resource allocation formula of high precision in the name of promotion of equity is largely fruitless given the impossibility of measuring the true need for, and costs of, providing health care, especially with the limited data available. The inclusion of measures of social deprivation is also poorly thought out. The availability of data from the 1991 census, which included a question regarding long-standing illness, together with the intention of the Department of Health to review the weighted capitation formula using this information may stimulate much work but little light. It is essential that the impact of resource allocation formulas is justifiable on grounds other than the composition of any particular formula. PMID- 8357371 TI - Health prevention messages may have paradoxical effect. PMID- 8357373 TI - Early diagnosis of staphylococcal toxaemia. PMID- 8357372 TI - Coronary bypass surgery should not be offered to smokers. PMID- 8357374 TI - Health policy and the courts: a new approach. PMID- 8357375 TI - Reader responds to April JMAG editorial. PMID- 8357376 TI - Unfunded research? I am shocked, shocked! PMID- 8357377 TI - Race and crack cocaine. PMID- 8357378 TI - Caffeine use during pregnancy: how much is safe? PMID- 8357379 TI - Article appreciated. PMID- 8357380 TI - Measles statistics inaccurately reported in poverty article. PMID- 8357381 TI - Patterns of internal echoes in lymph nodes in the diagnosis of lung cancer metastasis. PMID- 8357382 TI - Catheter-associated sepsis due to Alcaligenes xylosoxidans in a child with AIDS. PMID- 8357383 TI - Complications related to gastrostomy button placement. PMID- 8357384 TI - Simultaneous trapezium and Bennett's fractures. PMID- 8357385 TI - Psychosomatic medicine. PMID- 8357386 TI - Inhaled nitric oxide for the adult respiratory distress syndrome. PMID- 8357387 TI - The affliction of internal medicine. PMID- 8357388 TI - Hypertrophic sternal scars. PMID- 8357389 TI - Lipomatous hypertrophy of the interatrial septum. PMID- 8357390 TI - Refrigeration of used multidose vials. PMID- 8357391 TI - Doxapram in tubeless anaesthesia for microlaryngeal surgery. PMID- 8357392 TI - Isolated antibody to hepatitis B core antigen in blood donors and immune response to hepatitis B vaccination. PMID- 8357393 TI - Restenosis after coronary angioplasty: a proposal of new comparative approaches based on quantitative angiography. PMID- 8357394 TI - Primary hyperoxaluria type 1--liver transplantation before end-stage renal disease? PMID- 8357395 TI - Access to heart surgery for smokers. The NHS can't treat only saints. PMID- 8357396 TI - Psychiatry services for elderly people. Doctors should be in the front line. PMID- 8357397 TI - Injecting drug users in Edinburgh. General practitioners reluctant to prescribe. PMID- 8357398 TI - Sleep disorders. Liver damage warning with insomnia remedy. PMID- 8357399 TI - Triazolam. Weight of evidence supports increased risk. PMID- 8357400 TI - Sleep disorders. "Working treatment" best for night terrors. PMID- 8357401 TI - Chickenpox in pregnancy. Acyclovir for uncomplicated chickenpox? PMID- 8357402 TI - Antenatal HIV testing. Named testing is unevaluated and costly. PMID- 8357403 TI - Reporting deaths to the coroner. Death certification needs urgent overhaul. PMID- 8357404 TI - Asthma management guidelines. PMID- 8357405 TI - Lasers in surgery. PMID- 8357406 TI - Hereditary hydronephrosis and the short arm of chromosome 6. PMID- 8357408 TI - Preventive medicine: what does it prevent. PMID- 8357407 TI - Dangers of iron and vitamin C supplements. PMID- 8357409 TI - Screening and informed consent. PMID- 8357410 TI - More on compensating egg donors. PMID- 8357411 TI - Physical measurements and their reliability in low back pain patients. PMID- 8357412 TI - Re: Bleeding from a Meckel's diverticulum after the use of ibuprofen. PMID- 8357413 TI - Vaginal foreign body extraction by obstetric soft vacuum cup: an alternative to forceps. PMID- 8357414 TI - Disulfiram-induced lead intoxication. PMID- 8357415 TI - HCG positive mesothelioma. PMID- 8357416 TI - Animal research. PMID- 8357417 TI - You paid for the block. Why throw it away? PMID- 8357418 TI - Cricoid pressure and the laryngeal mask airway. PMID- 8357419 TI - Functional improvement in stunned myocardium. PMID- 8357420 TI - Comments on 'Blood vitamin and lipid levels in overweight and obese women', by A. Moor de Burgos et al. PMID- 8357421 TI - Comments on chlamydiosis. PMID- 8357422 TI - Screening for colorectal cancer: the accuracy of fecal occult blood. PMID- 8357423 TI - Walnuts and serum lipids. PMID- 8357424 TI - Duesberg: rights and wrongs. PMID- 8357425 TI - Reform options for peer review. PMID- 8357426 TI - Floppy eyelids and crack eye syndrome. PMID- 8357427 TI - More on condoms in school clinics. PMID- 8357428 TI - Hypercalcemia due to hard well water in a home hemodialysis patient. PMID- 8357430 TI - Injury to the superficial flexor tendon. PMID- 8357429 TI - Bleeding time and oral anticoagulant therapy. PMID- 8357431 TI - Update on drug therapy for HIV and related infections in adults. PMID- 8357432 TI - There is a need to modify the Sprotte needle. PMID- 8357433 TI - Checking anaesthetic machines. PMID- 8357434 TI - Impedance plethysmography and DVT diagnosis. PMID- 8357435 TI - More on the doctor's anguish. PMID- 8357436 TI - Alopecia areata, topical minoxidil, and balanced reviews. PMID- 8357437 TI - C reactive protein and neutrophil band forms in neonates. PMID- 8357438 TI - Treatment of ethylene glycol poisoning. PMID- 8357439 TI - Is surgery in Costa Rica really cheaper? PMID- 8357440 TI - Diet and colorectal adenomatous polyps. PMID- 8357441 TI - Lactic acidosis and AIDS. PMID- 8357442 TI - [Immunologic risk in blood transfusion]. PMID- 8357443 TI - [Passive transmission of granulo-agglutinating anti-HLA antibodies without pulmonary involvement]. PMID- 8357444 TI - [Practice of delayed autologous transfusion in Saint-Louis (Senegal)]. AB - In Saint-Louis' Regional Hospital, transfusional risks and blood shortage led us to introduce the delayed autologous transfusion despite a great number of difficulties. Our study aimed at finding the most adapted technique to the conditions in an African peripheral hospital, and lasted four months (from April to July 1992). In this paper, our first results are given that encourage us to continue in this way. PMID- 8357445 TI - [HIV seropositivity in blood donors from 1990 to 1992: prevalence, estimation of residual risk of transfusion-related infections and epidemiology]. AB - In France, HIV seroprevalence in blood donations still decreased from 1990 to 1992 with an important diminution in 1992, in first time donors as well as in regular donors. During the last 1992 semester, this prevalence reached 0.051%: 0.19% and 0.026% in donations from first time and regular donors respectively. The residual risk was estimated to be 1 for 580,000 donations in 1992 (CI 95% = 1/2,000,000 to 1/330,000). Sex ratio was 3.7 and 3.4 in 1990 and 1991 and increased to 5.5 in 1992 due to a very small number of seropositive women, which seems to be an important epidemiological indicator. The major at-risk group is still represented by homo-bisexual men. PMID- 8357446 TI - [Immunologic aspects of bone marrow transplantation]. AB - Allogeneic bone marrow transplantation is concerned by immunology by at least two aspects: the first one is the acceptance of the graft by the host and reciprocally and the second one is that it constitutes an unique human model of immune reconstitution. In this review of the immunological aspects, we deal with the selection of the bone marrow donor (related or not) especially on the base of HLA compatibility and the graft-versus-host disease (GVH) with the clinical manifestations, the usual treatments, the supposed cellular mechanisms and the risk factors of developing such complications. The graft versus leukemia effect (GVL) which may be linked to the GVH disease and the mechanisms of rejection and take of the graft are also reviewed as well as the immune reconstitution following the immune deficiency due to the conditioning treatment and the occurrence of a GVH disease. PMID- 8357447 TI - [Description and validation of a flow cytometric method to estimate residual leukocytes in leukocyte-depleted red cell concentrates]. AB - We describe a flow-cytometric method for estimating residual white blood cells (WBC) counts in WBC depleted blood components, namely units of packed red cells. The method uses fluorescent staining of nuclear ADN with ethidium bromide. WBC nuclei are discriminated from background events using fluorescence ratio (585 nm versus 650 nm). A facultative procedure of concentration is described, in order to get better sensitivity at very low WBC counts. Main steps of validation are dilution assays and correlation with hemocytometer counts. The method can be used to explore very low concentrations (less than 100 WBC/ml) and should be useful in quality control of blood products. PMID- 8357448 TI - [Irregular erythrocyte antibody screening using gel-test. Analysis of 35,882 samples]. AB - The results of screening for irregular blood-group antibodies in 35,882 blood specimens using the gel-test method were analysed. The samples came from different clinics and hospital units. 1,179 samples from 728 different individuals (3.2%) contained one or several irregular antibodies. The gel low ionic strength antiglobulin test detected Kell, Duffy, and Ss antibodies with a normal frequency compared to bibliographic data, whereas Kidd antibodies seemed to be abnormally infrequent. The best detection of Rhesus antibodies was obtained with the gel enzyme test (papain). The prevalence of cold, naturally occurring, anti-Lewis and anti-P1 antibodies was low. The gel enzyme test with papain treated red blood cells seems to be necessary for detecting Lewis antibodies (only 10 out of 95 were detected with the gel low ionic strength antiglobulin test). As a counterpart, the gel enzyme test also detected many antibodies with doubtful clinical significance: anti-E and anti-Cw reacting only with the gel enzyme test, autoantibodies with Rhesus specificity (82 examples), antibodies mimicking Jka (4 examples) and S (1 example) specificities in individuals with the corresponding antigen. PMID- 8357449 TI - A comparison of alcohol-related driving behavior of white and nonwhite North Carolina drivers. AB - This paper broadens the knowledge of drinking/driving behavior by examining the involvement of North Carolina (NC) nonwhite drivers in alcohol-related (A/R) crashes and fatal crashes involving alcohol for the period of 1980 through 1988. The study identifies an A/R crash involvement problem for nonwhites, particularly nonwhite males above the age of 25 and nonwhite females above the age of 54. For ages 25 and higher, the A/R crash rates per licensed nonwhite male are at least twice those of white (Euro-caucasian) males. In addition, the driving while intoxicated (DWI) arrest rates per driver are approximately twice as high for nonwhite males as for white males of the same age. Through analysis of other data related to arrests for drinking and driving, single-vehicle nighttime (SVNT) crashes, breath alcohol concentration (BAC) levels of those arrested for DWI, and those involved in A/R crashes, and blood alcohol concentration of those involved in fatal crashes, a series of alternative explanations for this nonwhite involvement are examined. It is concluded that while nonwhite males and females may be involved in more crashes than whites at the same BAC level (as hypothesized by other researchers), there is also evidence that nonwhites appear to drive more often after drinking and also drive at slightly higher levels of BAC. PMID- 8357450 TI - Development of a work behavior taxonomy for the safety function in industry. AB - A safety job activity questionnaire incorporating 24 job tasks was developed for describing the safety function within industry. This instrument was mailed to a stratified-proportionate sample of 1,190 working safety professionals representing 10 major industrial categories. Respondents rated the relative importance and amount of time spent on each of the 24 job activities. The overall response rate was 40%, producing 465 usable questionnaires. Factor analytic techniques were applied to each set of ratings to derive the principal dimensions of the safety position. Similar five-factor solutions emerged for both importance and time spent, accounting for 56% and 52% of the variance, respectively. The five job dimensions were: (i) serving as safety consultant and advisor, (ii) coordinating compliance and control activities, (iii) assessing the effectiveness of controls, (iv) analyzing hazards and losses, and (v) conducting specialized studies and reviews. Respondents, classified by industrial group and size of operation, were then compared using the job dimensions from the factor analyses. There were very few differences in the safety function across different industries or sizes of operations. PMID- 8357451 TI - Subjective probability of accident and apprehension in relation to self-other bias, age, and reported behavior. AB - Responses from over 900 male drivers were examined on items measuring the subjective probability of two adverse driving scenarios (accident and apprehension) for a number of speeding and drink-driving-related events. The items were constructed to focus on self versus average referent driver comparisons. Respondents were categorised into "offenders" and "non-offenders" according to their reported behaviour concerning speeding and drink-driving. The data were analysed using repeated measures analysis of variance. The results indicated that both accident and apprehension are seen as less probable when self is the reference compared to the average driver. There was evidence to suggest that this self-favouring bias did vary over presented scenarios. It was suggested that such perceptions may vary in relation to the perceived influence of driver skill within scenarios. Weak age effects were found, but it was concluded that, generally, self-favouring biases were common across all age groups. Concerning the offender/nonoffender classification, the results indicated that speeders and drink-drivers generally perceived the probability of apprehension and accident as being lower than did the nonoffender groups. There was no evidence to suggest that self-average driver biases were associated with offender/nonoffender grouping. PMID- 8357452 TI - The effects on accidents of compulsory use of daytime running lights for cars in Norway. AB - The use of daytime running lights was made mandatory for new cars in Norway in 1985 and for all cars in 1988. This paper examines the effectiveness of this regulation as an accident countermeasure. The paper relies on the same study design and method of analysis as previous studies of similar laws in Finland and Sweden. Four hypotheses concerning the effects of daytime running lights are tested. None of them was supported. The total number of multiparty accidents in daylight was not reduced. Pedestrian accidents and accidents in twilight were not reduced. The number of rear-end collisions increased by about 20%. Daytime running lights appear to reduce daytime multiparty accidents only during summer (by about 15%) and only for multivehicle accidents, excluding rear-end collisions. The possibility that confounding factors may have influenced study results is examined. It is concluded that such an influence cannot be ruled out. The discussion of the results highlights the difficulties of reaching clear and defensible conclusions in nonexperimental accident research of the kind reported in this paper. PMID- 8357453 TI - Typical accidents encountered by assembly workers: six scenarios for safety planning identified using multivariate methods. AB - This study highlights the most typical accidents encountered by assembly workers employed in a variety of different workshops at a large automobile and truck factory in Sweden. Following site visits and the collection of data from accident registers, statistics on 28 accident characteristics were compiled on the basis of the 145 accidents involving assemblers in 1986 and 1987. For data treatment, two statistical methods complemented one another: the factorial analysis of correspondence (FAC) and the hierarchical ascendant classification (HAC). Six typical accident profiles were extensively portrayed, quantified, and illustrated graphically: overexertion; falls and stumbling; injuries related to the handling of tools; superficial wounds to the (left) hand; cuts/pinches from moving machine parts and the handling of objects; miscellaneous blows from work pieces. The distribution of these types of accidents across the workshops was studied. It is emphasized that the search for typical accident patterns using multivariate statistical methods helps to structure and define the accident problems of a target group and therefore provides benefits for the evaluation of the need for preventive measures. PMID- 8357454 TI - Alcohol and drug use among motor vehicle collision victims admitted to a regional trauma unit: demographic, injury, and crash characteristics. AB - This study examined the incidence of alcohol and drugs in a sample of seriously injured motor vehicle collision victims, and differences related to pre-crash use of alcohol and/or other drugs on demographic variables, injury severity measures, and crash variables. The sample selected were all motor vehicle collision admissions to the Regional Trauma Unit at the Sunnybrook Health Science Centre in Toronto, Ontario, over a 37-month period (N = 854). Prospective demographic and injury-related information were collected from hospital charts, and crash data were collected from motor vehicle collision police reports. Blood samples were routinely collected on admission and tested for blood alcohol concentration (BAC). We found 32.0% of the BAC-tested motor vehicle collision admissions and 35.5% of drivers tested positive for blood alcohol. The drivers' mean BAC on admission was found to be 145.2 mg/100 ml, and the mean estimated BAC at crash time was 181 mg/100 ml. Drug screens were performed on a two-year subsample (n = 474), of whom 339 were drivers. Drug screens revealed that 41.3% of drivers tested positive for other drugs in body fluids, and 16.5% were positive for alcohol in combination with other drugs. Other than alcohol, the drugs most frequently detected in the drivers were cannabinoids (13.9%), benzodiazepines (12.4%), and cocaine (5.3%). Investigation of differences on demographic, injury, and crash characteristics related to precrash use of alcohol and/or drugs yielded significant findings. In the drug screened sample we found sex, admission type, and occupant status were related to precrash alcohol use. Also, use of drugs was found to interact with admission type and mean BAC on admission. Elapsed time was found to be significantly different for BAC by other drug use, with a greater length of elapsed time found for the subjects testing other drug positive but BAC negative. We found that BAC-positive drug-screened drivers were significantly more likely to be male, involved in a single-vehicle collision, not wearing a seat belt, ejected from the vehicle, and travelling at higher speeds than BAC negative drivers. No significant differences were found between BAC and/or other drug use on injury severity measures. PMID- 8357455 TI - Does the use of child safety seats increase as a result of loan schemes? AB - This population-based study carried out in central Sweden is concerned with parents' attitudes towards infant restraints in cars and whether the loaning of infant car seats leads to increased use during and after the first nine months of the infant's life. Of 937 infants born in a defined geographical area with a population of 86,000 (test group) 84.8% of parents borrowed a seat for their newborn infants. No such loan was available to the control group. Use increased greatly during the first nine months (loan period) when the seat was freely available to the test group; but no important difference emerged between the test and control groups after nine months of age concerning long or short journeys. In the test group use of the seat was lower for short than for long journeys during the first nine months. In the control group, in which the parents had to obtain their own seat, the difference was marginal. A total of 19 accidents involving infants in the study group occurred during a one-year period. In some respects the findings of the present study differ from those of two other comparable studies, particularly regarding the number of parents who chose to borrow a seat, the age of the child when starting to use the seat, and parents' views on the comfort of the seat. PMID- 8357456 TI - Self-bias in older drivers' judgments of accident likelihood. AB - Drivers generally perceive their own chance of having a road accident to be significantly lower, and their own skill to be greater, than that of their peers. Previous research has shown this effect to be reduced in middle-aged drivers as opposed to young ones. This study examines the extent to which this positive self bias in relation to driving continues or changes with increasing age beyond 50 years, examining the relationship of self-bias to driving experience and also to locus of control. Eighty subjects aged between 50 and 79 completed a self-rating questionnaire on the likelihood of having different types of accidents (driving and nondriving) when in control themselves and when someone else was in control, comparing themselves to "average others" of different ages. In the nondriving accidents, the self-bias for people in their 70s comparing themselves with an average other aged 70, was far greater than for those in their 50s (comparing themselves with an average other aged 50). In the driving accident scenarios there was little self-bias at all when the comparison was with same aged peers only. In this analysis, people in their 50s showed no self-bias, whereas their self-bias had been considerable when comparing themselves with three age groups (30s, 50s, and 70s were used). Amount of positive self-bias generally decreased with increasing age, increased with greater current driving experience (mileage), and increased with amount of perceived control. Number of years of driving experience had no effect. However, in regression analysis on the same aged peers comparison, only internality of locus of control was a significant independent predictor of the variance in self-bias in the driving situation. Age and current driving experience were not significant independent predictors. Results were discussed with reference to the importance of the comparison group when assessing differences in self-bias and to the potential implications for road safety education. PMID- 8357457 TI - Work-related road fatalities in Australia, 1982-1984. AB - A study of work-related fatalities, based on coroners' records, has provided national data on work-related road fatalities. A total of 1,544 work-related fatalities were identified over 1982-1984. Of these, 600 (39%) resulted from injuries sustained in road vehicle accidents on public roads; 366 (24%) in the course of work, and 234 (15%) while commuting between home and work. These figures are likely to underestimate work-related road fatalities because the coroners' records often did not contain the required information. The incidence of road fatalities declined slightly over the three years, although the proportion amongst all work-related fatalities remained constant. The at-work victims tended to be older than victims of road death generally. Fifty-six percent of the at-work cases were in the occupational group "drivers, road transport". Articulated trucks accounted for 41% of the at-work cases. Drivers made up 79% of the at-work group. In contrast, drivers accounted for only 38% of all road deaths. Two-thirds of the at-work road fatalities occurred outside capital city districts, the proportion of nonmetropolitan cases being highest for deaths involving articulated trucks. This is striking, in view of Australia's highly urbanised population. Blood alcohol data were available for 76% of the at work cases and 79% of the commuting fatalities. Of these, 15% and 13%, respectively, had a blood alcohol of 0.05 g/100mL or more. In contrast, 6% of other workplace fatalities for which blood alcohol data were available had such levels. This difference may reflect more assiduous blood-alcohol testing of road accident victims.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357458 TI - Application of an injury surveillance system to injuries at an industrial facility. AB - We developed a computerized surveillance database employing the Abbreviated Injury Scale (AIS) and sampled three months of nonfatal injuries at a large industrial facility. Data from 197 injury visits to the plant medical department were collected. With the addition of some new AIS codes for injuries specific to the workplace, most injuries could be coded and severity scores calculated with good interrater reliability. Neither Maximum AIS nor Injury Severity Score (ISS) predicted restricted or lost work time. Because of its ease of automation and reliability, the AIS can serve as a useful tool for occupational injury surveillance, but its current severity scoring system is not predictive of disability. PMID- 8357459 TI - The effect of laser speed-measuring devices on speed limit law enforcement in Charleston, South Carolina. AB - Drivers exceeding the speed limit by more than 10 mph were identified and ticketed by the Charleston County, South Carolina police using two types of speed measuring devices: conventional police radar and a new laser device. The two types of enforcement were used alternately on the same roads at similar times. Under the laser enforcement condition, the police issued 534 tickets (54%) compared with 457 (46%) under radar enforcement. The increase in tickets issued under laser enforcement was observed at three of the four study sites, and the number of tickets per traffic volume increased at two of the three sites for which traffic volumes were available. Speeders ticketed under the laser enforcement condition were four times as likely to have radar detectors as those ticketed under the radar enforcement condition. Most of the additional speeders caught by the laser were using radar detectors. These data indicate that some speeders with radar detectors are avoiding detection when the police enforce the limit with radar. PMID- 8357460 TI - A temporal analysis of rain-related crash risk. AB - The study presents empirical evidence of accident risk during and following rain events in the cities of Calgary and Edmonton, Canada. The matched sample approach is used to examine data for 169 rain events and over 15,000 accidents that occurred during the years 1979-1983. The overall accident risk during rainfall conditions was found to be 70% higher than normal. The data suggest that accident risk returns to normal as soon as the rainfall has ended, despite the lingering effects of wet road conditions. PMID- 8357461 TI - Exposure corrected risk estimates for childhood product related injuries. AB - This study assesses the effect of exposure correction on injury risk estimates for children, using Chicago-area survey data on age-specific exposure of children to seven products: amusement park rides, sleds, bunkbeds, skateboards, fireworks, toboggans, and air guns and rifles. National Electronic Injury Surveillance System estimates for 1987 were used as numerators with two denominators: (i) uncorrected age-specific U.S. Census estimates for 1987 and (ii) these estimates corrected for exposure. Except for bunkbeds, skateboards and sleds, corrected injury risk decreased as age increased. Uncorrected population injury rates underestimated the risk posed to product-using children, especially those who are youngest and those who use skateboards. PMID- 8357463 TI - Road accident trends in Nigeria. AB - A study of road accident trends in Nigeria between the period 1960 and 1989 revealed a sharp increase in fatal accident occurrence. Between 1960 and 1969, it was observed that over 18,000 deaths occurred as a result of road accidents. By the third decade (1980-1989), this figure had increased to about five times, i.e. more than 92,000 deaths. Reasons for the severity of road accidents in Nigeria are discussed. PMID- 8357462 TI - Incidence of alcohol and drugs in fatally injured car drivers in Norway. AB - Blood samples from 159 fatally injured drivers from 1989 and 1990, corresponding to 57% of all fatally injured drivers in Norway during this period, were analysed for alcohol and psychoactive drugs. Alcohol was found in 28.3% of the drivers, 27.0% above the legal limit of 0.05%. Drugs were found in 16.4% of the drivers; benzodiazepines and tetrahydrocannabinol were the drugs most frequently found. Among 79 drivers fatally injured in single-vehicle accidents, 41.8% were positive for alcohol and 21.5% were positive for drugs. PMID- 8357464 TI - Synthesis and pharmacological screening of a group of piperazine derivatives. Analgesic activity. AB - Fifteen original piperazine derivatives were synthesized: 11 esters of 1 substituted-4-(3'-phenyl-3'-hydroxypropyl)-piperazines with acetic, propionic, benzoic and phenylacetic acids and 4 symmetrical esters of 1,4-bis-(3'-phenyl-3' hydroxypropyl)-piperazine with acetic, propionic, benzoic and phenylacetic acids. The compounds were tested with respect to their analgesic and behavioural activity, as well as toxicity. Three nociceptive tests were used: chemical intraperitoneal irritation with acetic acid, thermal contact irritation and thermal radiation irritation. The tests were performed on albino mice breed H. All tested compounds were biologically active and showed analgesic effect. The "therapeutic index" was determined on the basis of the mean effective doses (ED50) and the mean lethal doses (LD50). Most favorable "therapeutical" indices were distinguished in 1,4-bis[3'-phenyl-3'-acetoxypropyl]-piperazine (12), 1 benzhydryl-4[3'-benzyloxypropyl]-piperazine (10) and 1-benzhydryl-4[3'-phenyl-3' phenylacetyloxypropyl]-piperazine (11). PMID- 8357465 TI - Synthesis and antimicrobial activity of some new indolo[2,1-b]quinazolin 6(12H)ones. AB - A series of indolo[2,1-b]quinazolin-6(12H)ones 4a-i was prepared and tested for the antimicrobial activity. The synthesis of the new compounds and the results of the antimicrobial screening are reported. PMID- 8357466 TI - Fungicidal activity of new O-derivatives of phenylpyridylketoximes. AB - Some alkyl- and acylderivatives of phenylpyridylketoximes were prepared and tested in vitro and in vivo against fungal plant pathogens of different taxonomic classes. The tested compounds exhibited remarkable activities, especially when an ethyl group was present on the oxime function. PMID- 8357467 TI - Synthesis of 4-quinolylazide derivatives and evaluation of their antitumor and antimicrobial activity. AB - Synthesis and pharmacological evaluation of a series of 4-quinolylazide derivatives are reported. These were screened against P388 lymphocitic leukemia in mice, but they resulted inactive. All the compounds were also tested for their antimicrobial activity against gram-positive, gram-negative strains and fungi; only three derivatives exhibited poor activity. PMID- 8357468 TI - Synthesis and antimycobacterial activity of some 4-pyridinecarboxyamidrazone derivatives. AB - A series of N1-aryliden-4-pyridinecarboxyamidrazone derivatives was prepared. Some of the synthesized compounds showed interesting in vitro antimycobacterial activity against some strains of Mycobacterium and clinical isolates of Mycobacterium tuberculosis. PMID- 8357470 TI - [Risk factors for allergy to hymenoptera stings]. AB - Hymenoptera stings are common and potentially serious. The clinical, paraclinical and therapeutic aspects of allergy to hymenoptera venom are being better and better understood. A retrospective descriptive enquiry of hymenoptera stings in 270 consultations in a Central General Hospital has established three risk factors in the possibility of a serious reaction (R.A.G.): Men: 2.4 times more allergic reactions (R.A.). Severity of R.A. increases with age, especially after 50 years. Hornet stings have a risk 5 times greater than that of bees and 4.3 times greater than wasp. PMID- 8357469 TI - N-substituted 4-carboxy-1-phenyl-1H-pyrazole-5-propanamides with antiinflammatory, analgesic, antipyretic and platelet antiaggregating activities. AB - The synthesis of a series of N-substituted 4-carboxy-1-phenyl-1H-pyrazole-5 propanamides by reaction of 1-phenyl-1H-oxepino[4,3-c]pyrazole-4(8H),6(7H)-dione with aromatic primary amines is described. Some amides showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as moderate antiinflammatory, analgesic and antipyretic activities in rats or mice. PMID- 8357471 TI - [Preliminary study of the importance of trace elements in immunostimulation]. AB - Stimunal is an original immuno-stimulant of which the action is between adapted therapy and probability. It has a composition of trace elements which are usually recognised to be useful for the function of immune defences and this requires a clinical research of two populations: Those subjects who are predisposed to infections of the upper and lower respiratory tract. Those allergic subjects who do not respond overall to the protocols for specific desensitisation. The study of 27 cases shows a modality of modest but not negligible response in particular in 8 patients who showed objective clinical and complementary improvement. This study should be extended to a larger sample. PMID- 8357472 TI - [Double-blind comparative study of terfenadine and cetirizine in chronic idiopathic urticaria]. AB - Our randomised study in parallel groups, double-blind double placebo, has compared the efficacy, onset of action and safety of terfenadine and cetirizine in chronic idiopathic urticaria. Over a fourteen day period, patients of the first group received a tablet containing 120 mg of terfenadine, those of the second group a tablet containing 10 mg of cetirizine. Symptoms were assessed every two hour period for the ten first hours on the first day (D1), and before and at the end of the study by the investigators. 193 patients were included by 48 dermatologists between May 1989 and July 1990. Both groups were well matched for all general characteristics and baseline symptoms scores. The onset and the intensity of regression of symptoms (pruritus, erythema and discomfort during sleeping time) were similar in both treatment groups public physicians: improvement of pruritus in over 90% of the patients. Meanwhile the tolerability was good or excellent for dermatologists and allergologists for 92% of the patients under terfenadine against 81% of the patients under cetirizine (p < 0.05). Adverse events (fatigue and drowsiness) were significantly reported less frequently (p < 0.05) in patients on terfenadine (19%) than on cetirizine (33%). This study confirms the efficacy of terfenadine compared with cetirizine in the treatment of chronic idiopathic urticaria. Adverse events were less significant for terfenadine (n = 18) than for cetirizine (n = 29) (p < 0.05). PMID- 8357473 TI - [Sublingual specific immunotherapy for rhinoconjunctivitis caused by grass pollens]. AB - Fifty eight patients with rhino-conjunctivitis caused by grass pollen were included in a double-blind study in which they received, by the sub-lingual route over 5 months, either a solution of purified and standardised allergen or a placebo. Assessment of the effect of this immunotherapy, which was done with drops of Stallergenes "5-grass pollen" was by clinical symptoms and the use of authorized drugs and treatments. Compared with the placebo group, the patients on active treatment showed significantly less (P = 0.05 to P = 0.01) rhinitis symptoms (sneezing and rhinorrhea) and conjunctivitis (reddening and tears) during the pollen season. Consumption of nasal cromoglycate solution, of betamethasone and dexchlorpheniramine was significantly lower (p = 0.01) in the desensitised group. Secondary effects were negligible. From this study, it can be concluded that immunotherapy with grass pollen extract, by the sub-lingual route, of patients with rhino-conjunctivitis who were sensitive to these allergens, is efficacious, easy to do, economic and sure. PMID- 8357474 TI - [Determination of total IgE (tIgE) and specific IgE (sIgE) using the IMX and MATRIX techniques]. AB - This study, on 185 subjects, has given evaluation of total IgE by the IMX technique in comparison with CAP PRIST, and of the MATRIX* technique for the measurement of sIgE in comparison with the reference technique of CAP RAST**, skin tests and clinical history. The two techniques of CAP and MATRIX are judged to be comparable (Correlation percentage 88.2%). The correlation of MATRIX with skin tests and clinical history is satisfactory (respectively 85.9% and 95%). The results were obtained with four allergens (D. pteronyssinus, Timothy grass, cat and dog). Separate assays confirmed the reliability of the technique. PMID- 8357475 TI - Studies of tissue cultured sliced dermis as a skin substitute. AB - A dermis slicer designed by the authors enabled us to prepare about 10 sheets of sliced dermal grafts (SDG), 300 micron(s) thick, from the dermis harvested from the back or buttocks of adult patients during operations. Such a sliced dermal sheet was stretched with one surface stuck on the base of a culture dish. It was then incubated in Dulbecco's essential medium for tissue culture, to which epidermal growth factor had been added. By the first week only its upper side was epithelialized from epithelial components in sliced dermis. The formation of basement membrane with anchoring fibrils was confirmed by electron microscopy. The appearance of type IV collagen and laminin was observed between epithelialized basal cells and the dermal layer. Thus, it is thought that the SDG is useful not only for immediate grafting, when epithelialization follows, but also as a substitute for free split thickness skin grafts following tissue culture. PMID- 8357476 TI - A novel approach to extend the survival of skin xenografts without entailing general immunosuppression or systemic toxicity. AB - The feasibility of using antigenically disguised skin xenotransplants to cover extensive burns for a suitable time lag without administering immunosuppressive drugs was tested experimentally. Pieces of human skin that had been preincubated for 3 h at 37 degrees C with either mouse anti-human beta 2-microglobulin monoclonal antibody (beta 2m-McAb) or PBS (controls) were grafted onto the backs of immunologically competent Swiss mice, and the time required for their rejection or substitution by normal autogenous skin was determined. Thus, it was found that the beta 2m-McAb-pretreated xenografts had a significantly longer mean survival time than the control grafts. An even longer skin xenograft MST was obtained when beta 2m-McAb was repeatedly injected, at weekly intervals, just beneath the transplants. Parallel immunohistochemical studies showed that the beta 2m-McAb entered the grafts and was bound to its targets both in epidermis and dermis. Moreover, a small amount of beta 2m-McAb administered at the outset significantly hindered the reactive proliferation of primed mouse spleen cells cultured in the presence of human epidermal cells. Finally, neither toxic effects nor a weakening of immune competence were elicited by repeated intraperitoneal injections of beta 2m-McAb. Therefore, it seems expedient to propose the use of beta 2m-McAb to delay the rejection of skin xenografts as this antibody harmlessly prevents, wholly or in part, the activation of the recipients' lymphocytes. This would positively aid any patient urgently needing xenograft cover of extensive burns. PMID- 8357477 TI - Effect of corticotropin releasing factor on acid-base alterations and bacterial translocation in a murine model of thermal injury. AB - Corticotropin-releasing factor (CRF) is a 41 amino acid polypeptide produced by the hypothalamus which has been shown to decrease inflammation and tissue oedema when administered following burns, cold and acid injuries in some animal models, and to increase mesenteric blood flow. We determined whether systemic administration of CRF to burned mice would decrease metabolic acidosis and protect the gastrointestinal (GI) tract from ischaemic injury leading to bacterial translocation (BT). Synthetic CRF was administered by intraperitoneal injection in doses of 20 and 200 micrograms/kg to mice immediately following 25 and 32 per cent TBSA burn injuries; the doses were repeated at 8 and 16 h postburn. Severe metabolic acidosis, measured 12 h after burn injury, was not improved in mice which received CRF treatment. Bacterial translocation, measured by quantifying bacteria in mesenteric lymph nodes harvested from animals 48 h postburn, was also not decreased with CRF treatment. CRF does not improve general tissue perfusion nor decrease GI derangements leading to bacterial translocation in this animal model of burn injury. PMID- 8357478 TI - Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing. AB - The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite (Smith & Nephew) and a conventional topical antibiotic dressing (Soframycin, Roussel) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean time to complete healing (complete epithelialization) was 6.2 +/- 1.6 days in the phenytoin treated group (30 patients), compared to 8.6 +/- 2.2 days with OpSite (15 patients), and 12.6 +/- 3.4 days in the 15 Soframycin-treated patients. The differences between the treatment groups were significant at P < 0.001. Mean pain scores were also lower in the phenytoin-treated group, 0.40 +/- 0.55 vs. 0.66 +/- 0.60 with OpSite (P < 0.05) and 1.4 +/- 0.50 with the conventional dressing (P < 0.001). Both phenytoin and OpSite were superior to the Soframycin dressing with respect to bacterial contamination and wound infection as measured by Gram stains of wound smears, swab and aspirate (OpSite) cultures, and clinical assessments (P < 0.001) carried out on the fifth day of treatment. No local or systemic adverse effects of the three agents used were noted. Phenytoin appears to be an effective, low-cost and safe method for the treatment of partial-thickness skin graft donor sites, comparing very favourably with, and in some aspects superior to, occlusive dressings. Further clinical use and evaluation of topical phenytoin are merited. PMID- 8357479 TI - Experimental study on alkaline skin injuries--periodic changes in subcutaneous tissue pH and the effects exerted by washing. AB - A skin alkaline injury model was constructed using rats and 2N-NaOH. The changes over time, paying special attention to subcutaneous tissue pH, were recorded and included a comparative study of the effect on subcutaneous tissue pH of washing with water at 1, 10 and 30 min after injury. After inflicting alkaline injury, the subcutaneous tissue pH reached its peak value at the 32nd minute and had not recovered to the pre-experimental level by the 90th minute. The peak pH values of the 1-, 10- and 30-min delays before washing groups were 7.97, 10.57 and 12.17, respectively. When washing was started within 1 min of injury the tissue pH values did not exceed 8.00. Washing had virtually no effect on lowering the raised pH levels when the delay between injury and the start of washing was 10 and 30 min. PMID- 8357480 TI - A burn patient resuscitation therapy designed by computer simulation (BET). Part 1: Simulation studies. AB - This study presents an analysis of the fluid, electrolyte and colloid needs of burn patients during the shock phase. A digital simulation technique was used which had previously been validated and published in burned patients (Roa et al., 1988). After analysing the repercussions of both burns and various resuscitation procedures, a fluid therapy method (BET) has been designed using a burn patient simulator, which has been characterized by its effectiveness and minimal side effects. The characteristics of the BET method are a low volume of infusion resuscitation solution (220 ml/h/m2 burned body surface area (BBSA)) and a rapid and large volume of colloidal substances (with colloid concentrations of 10, 7.5 and 5 g/100 ml during the first three 8 h periods of the first postburn day and 2.5 g/100 ml until the 40th h postburn). PMID- 8357481 TI - A burn patient resuscitation therapy designed by computer simulation (BET). Part 2: Initial clinical validation. AB - The clinical results obtained from the first 40 burned patients resuscitated with 220 ml/h x BBSA (m2) of human serum albumin with concentrations of 10, 7.5, 5 and 2.5 per cent in lactated Ringer's (0-8, 8-16, 16-24 and 24-40 h post injury respectively), which we have called BET fluid therapy, were compared with those obtained in 58 patients resuscitated with lactated Ringer's 4 ml/kg of body weight/%BBSA during the first 24 h after burning. The results confirm the effectiveness of the BET form of fluid therapy during the shock phase after burning. The BET fluid therapy method differs from other procedures because of its lower volume of infused resuscitation solution with the rapid infusion of large amounts of colloid. These preliminary results have encouraged us to continue analysing this new method of fluid therapy. PMID- 8357482 TI - Burns in Madras, India: an analysis of 1368 patients in 1 year. AB - Analyses were made of 1368 patients who attended Kilpauk Medical College Hospital, Madras with burns between 1 May 1987 and 30 April 1988. Nine hundred and sixty-five patients were admitted, of whom 505 died. The peak age incidence was in young adults (11-30 years; 58.9 per cent of all burns). Three quarters of the patients came from the low family income group, 39.5 per cent were illiterate and 86.2 per cent of burns occurred in the home. Of those admitted 81 per cent of the injuries were flame burns; in 31.3 per cent the burn affected more than half of the body surface. Of the 505 deaths 94.8 per cent were the result of flame burns (at least 323 being caused by kerosene), and 20.4 per cent were suicide. Most of the deaths (91 per cent) occurred in the first 5 days. The urgent need for burn prevention in the Madras area is discussed. PMID- 8357483 TI - Infection and antibiotic therapy in 4000 burned patients treated in Milan, Italy, between 1976 and 1988. AB - The pathogenic flora, isolated from burn wounds of patients admitted to a burn care unit during the years between 1976 and 1988 were typed and the in vitro susceptibility to antibacterial agents was recorded. Between 1976 and 1988 the general therapeutic approach was changed three times, in congruence with the prevalent nosocomial bacterial resistance. The most frequent isolates were: Pseud. aeruginosa, Staphylococcus aureus, Enterococcus spp., Proteus mirabilis, Escherichia coli, Enterobacter cloacae, Klebsiella spp. and other Enterobacteriaceae, such as Acinetobacter, Citrobacter. The most striking finding was the increase in antibiotic-resistant Enterococcus isolates. Staph. aureus, Klebsiella and E. cloacae showed susceptibility to cephalosporins, imipenem, pefloxacin, vancomycin; Enterococcus susceptibility to pefloxacin and vancomycin, and Pseud. aeruginosa sensitivity to piperacillin, amikacin, tobramycin was generally good. E. coli showed a satisfactory susceptibility on average, and P. mirabilis showed a good sensitivity to piperacillin, cephalosporins, amikacin, tobramycin, aztreonam and imipenem. Thus, the general bacterial flora and susceptibility have remained mostly unchanged over the years, with the conspicuous exception of Enterococcus spp. and E. cloacae, which demonstrated a marked increase in incidence, with a concomitant dramatic decrease in the sensitivity of Enterococcus spp. to antibiotics. PMID- 8357484 TI - Entry to the burns team: stressors, supports and coping strategies. AB - Employment as a member of a multidisciplinary burns team presents the individual with an enticing professional and personal challenge. Patients sustaining major burns require intense physical and psychological rehabilitation over an extended period of time, often drawing upon the services of a sole therapist. Although more attention is being paid to professional issues of 'burn-out' and general care of the health professional, there has been little published with regard to actual stressors experienced by burn staff. An understanding of stressors faced, and current support systems utilized, by an occupational therapist in the first 12 months in a major burns unit, illustrates the unique demands placed upon junior staff. Following this review possible coping strategies for the individual and institution at large are discussed. It is suggested that continuing education, supervision by senior staff and better staff/patient ratios, may facilitate an easier transition into the burns team and render staff better able to cope with continuing stressors. PMID- 8357485 TI - Epidemiology of burns in the Tel Aviv area. AB - Between 1 August 1988 and 31 January 1992, 421 burn patients were admitted to the Burn Unit at Beilinson Medical Center. Name, age, sex, month of the year, cause of burn, area and degree of burn and duration of stay in hospital were recorded. Of these patients, 37 per cent were treated surgically and the remainder were treated conservatively. The male to female ratio was 2:1. Burns occurred most frequently in July and January; the peak average age was the first decade of life. The most frequent cause in children was scalding (domestic burns), and in adults open fires (work accidents). Patients treated by early tangential excision and skin grafting (204 operations on 157 patients) had a shorter stay in hospital than conservatively treated patients. In accordance with others, we suggest that early surgery of burn injuries decreases morbidity and mortality and leads to better aesthetic results and improved motor function. Secondly, burn injury can be prevented in children and the elderly by increasing safety measures at home, and in adults by enforcing strict safety measures at work. PMID- 8357486 TI - Chemical burn due to contact with soda lime on the playground: a potential hazard for football players. AB - Two football players were treated for chemical burns of their genitalia and medial thighs caused by contact with soda lime used to line a playground. The cases are reported and the unusual mechanism causing the injury is described. PMID- 8357487 TI - Acquired tracheo-oesophageal fistula following tracheal intubation in a burned patient. AB - A 27-year old male sustained a 60 per cent TBSA burn with inhalation injury following a road traffic accident. He developed respiratory distress on day 3 postburn, and was intubated and ventilated. He was noted to have greenish aspirate from his trachea on day 17 of ventilation. He succumbed from sepsis and died on day 21 post injury. At post-mortem, a large tracheo-oesophageal fistula (TOF) was found at the level of the cuff of the nasotracheal tube. PMID- 8357488 TI - A summary of the workshop on child and adolescent obesity: what, how, and who? PMID- 8357489 TI - Defining obesity in children and adolescents: epidemiologic approaches. AB - This article discusses the use of epidemiologic and statistical approaches in developing definitions of obesity for children and adolescents. Definitions of adult obesity have been derived from mortality data or from statistical data on reference populations. Both approaches pose problems when applied to children and adolescents. The choice of appropriate measurements can be difficult. Data on childhood weight and adult outcomes are sparse and hard to interpret. Statistical definitions based on reference populations are more straightforward, but require arbitrary assumptions that limit their usefulness for prevalence estimates or comparisons across age, sex, or race/ethnic groups. Examples illustrate some issues in defining childhood obesity, including a case study of two groups of researchers who used the same data sets, but arrived at different conclusions. At present there is no generally accepted objective definition of obesity for children or adolescents. PMID- 8357490 TI - Defining obesity in children and adolescents: clinical approaches. AB - For clinical utility, obesity should be defined as a condition of excess adipose tissue associated with adverse health outcomes. Based on a number of criteria, body mass index (BMI) (weight/height) is the most appropriate measure for clinical assessment of adiposity in children and adolescents. However, sufficient information regarding associations between adiposity and current or future morbidity is lacking. Available data suggest a definition of obesity based on adiposity alone would perform poorly as a clinical screening test for adverse health outcomes. In addition, labeling and attempted weight control therapy may produce more harm than benefit. Therefore, until better information regarding the risks of adiposity and risks of treatment are available, recommendations for weight control therapy should be focused primarily on those children and adolescents who currently manifest adiposity-related morbidity, those with a BMI above the 95th percentile, or those above the 85th percentile who perceive their adiposity to be a significant psychosocial problem. To produce a clinically useful definition of obesity, longitudinal data should be used to determine the sensitivities, specificities, and predictive values of comparative measures of childhood and adolescent adiposity for predicting current and future morbidity, and to evaluate the utilities of including characteristics such as age, age of adiposity rebound, persistence of increased adiposity, family adiposity, family morbidities, and fat distribution to improve predictive values and minimize misclassification. Weight control research should attempt to identify patient characteristics that predict long-term treatment success, treatment failure, and treatment side effects. PMID- 8357491 TI - Physical activity assessment in children and adolescents. AB - This article provides a review of the techniques that have been developed for measurement of physical activity in children and adolescents. Physical activity has been measured in youngsters using three major approaches: direct observation, heart rate or motion monitors, and self-report measures. Each of these techniques has relative benefits and deficiencies. Direct observation is a valid procedure requiring little interference and can provide good information concerning contextual variables (i.e., physical and social environment). However, direct observation is costly in terms of investigator and observer time. Motion sensors and heart rate monitors overcome problems associated with subject recall of activity and are less costly than direct observation. However, these instruments can be prone to technical problems and they provide no information concerning specific activities or the context in which activities are performed. Self-report and proxy report (e.g., by parents or teachers) techniques are relatively inexpensive, but their validity is limited by the ability of the subject (or proxy) to recall and report activity behavior. A major limitation in this field has been the lack of a "gold standard" measure of energy expenditure. The lack of such a criterion measure has precluded validation of the aforementioned activity measures as indicators of energy expenditure in children and youth. PMID- 8357492 TI - Obesity in children and adolescents: development of predictive equations and their application to epidemiologic studies. AB - Epidemiological studies of body fatness cannot be based on laboratory measures. One alternative is to analyze values related to body composition such as skinfold thicknesses, but it is better to apply an equation that accurately predicts a body composition variable. If an equation is to be developed, the choice of the dependent variable affects the selection of the independent variables to be tested for inclusion. The validation group should have a wide distribution of values for the dependent and independent variables. To develop an equation that works well on validation and with other groups, all possible sub-set regression should be applied, multicollinearity examined, and ridge and robust regression used if these are needed. An equation chosen from the literature should have been developed and tested by appropriate methods and it should be validated against data from a sub-group of the study sample. PMID- 8357493 TI - Obesity genes and diabetes induction in the mouse. AB - Obesity, a phenotype having high heritability in humans, constitutes the major risk factor predisposing an individual to non-insulin-dependent diabetes mellitus (NIDDM). However, most obese humans do not develop NIDDM, indicating that diabetogenesis entails a complex interaction between obesity genes and other predisposing susceptibility traits. The possible nature of some of these background modifiers is being elucidated by analysis of genetically obese mice. Mutations at loci on six different mouse chromosomes produce obesity, but development of insulin-resistant diabetes requires an interaction between the obesity mutation and other factors in the genetic background. Analysis of the interaction between three distinct obesity genes expressed on the same genetic background has shown that virilization of hepatic sex steroid metabolism mediated via aberrant shifts in sex steroid sulfotransferase activities is a prerequisite for diabetogenesis. The analogies between the development of a hyperandrogenized tissue state in obese mice with obesity-diabetes syndromes in humans are discussed. PMID- 8357494 TI - Genetic models of human obesity--family studies. AB - Childhood obesity is predictive of obesity as an adult, and individual differences in body weight relative to height (body mass index) in adults are important predictors of morbidity as well as mortality from atherosclerotic cardiovascular disease. The observation of strong familial correlations does not ensure that genes are involved in the determination of body mass index, because individuals in families share environments as well as genes. However, several recent studies have found evidence for both additive (polygene) and nonadditive (major gene) components. A question that results from these analyses is--what gene(s) has been inherited that carries an associated risk, most likely mediated by environmental exposures, for obesity? Studies to identify genetic loci linked to familial obesity should add to our understanding of the genetic factors involved in the determination of obesity and may lead to early identification of individuals and families at high risk for the chronic disorders that are associated with obesity. PMID- 8357495 TI - Genetic influences on energy expenditure in humans. AB - Variations in human energy expenditure are partly because of an influence of the genotype, even after control for the well-established concomitants of energy expenditure. Using the techniques of genetic epidemiology, we have found that about 40% of the variance in resting metabolic rate, thermic effect of food, and energy cost of low-to-moderate intensity exercise (< or = 5 times the resting metabolic rate) is explained by inherited characteristics. A significant genetic effect has also been reported for the level of habitual physical activity. The existence of a genotype-environment interaction has also been investigated. Thus, in response to chronic overfeeding, as well as negative energy balance, changes in the components of energy expenditure exhibit significant identical twin pair resemblance. Nutrient partitioning is emerging as a major determinant of the individual differences in metabolic rate responses to overfeeding or negative energy balance conditions. Taken as a whole, these observations consistently support the hypothesis that heredity plays a significant role in the various components of energy expenditure in humans. PMID- 8357497 TI - Metabolic efficiency of macronutrient utilization in humans. AB - Macronutrient utilization in humans is a complex phenomenon, with each macronutrient having its separate storage and utilization pathways. Carbohydrate and fat are to some extent interdependent, but while carbohydrate utilization is greatly dependent on intake, fat is not. The food quotient of the diet is important in determining how nutrients are utilized and stored, and thus is an important determinant of body composition. Also, the effect of these two macronutrients on food intake differs. The bioenergetics of utilization of the macronutrients are discussed. PMID- 8357496 TI - Strategies for the molecular genetic analysis of obesity in humans. AB - Studies of twins, adopted children, and some human populations indicate that body composition is significantly influenced by genetic factors. However, in no specific instance in either man or animals is the precise etiology of obesity known at the molecular level. Attempts to identify the molecular basis of obesity in humans have been hampered by difficulties in measuring food intake and energy expenditure with sufficient accuracy, as well as the apparent polygenic control of body composition in man. These constraints have stimulated interest in inbred animal strains, particularly mice, that have a genetic predisposition to obesity. Using the techniques of positional cloning, molecular markers flanking two autosomal recessive mouse obesity mutants (ob and db), which demonstrate a metabolic/behavioral phenotype similar to that observed in obese humans, have been identified. These markers are being used: (1) as starting points for chromosome walks to identify these genes, (2) as an aid in identifying genetically obese rodents prior to the development of the experimentally confounding obese phenotype, and (3) to investigate the possible contribution of the ob and db gene products to obesity in families segregating an obese phenotype. Additionally, genetic crosses segregating these obesity mutations are being used to identify "polygenes" that influence the severity of obesity and type II diabetes. Such studies may ultimately lead to the characterization of genes that influence the development and severity of obesity and non-insulin dependent diabetes (NIDDM) in humans. PMID- 8357498 TI - Metabolic rate and body composition of Pima Indian and Caucasian children. AB - A low metabolic rate for a given body size and body composition may be a risk factor for body weight gain. Because the prevalence of obesity exceeds 75% in the Pima Indian population, we investigated whether Pima Indian children have a low resting metabolic rate (RMR) when compared with Caucasian children. Body composition (bioelectrical resistance) and RMR were measured in 43 Pima Indian children (22 male/21 female, means +/- SD = 9.9 +/- 1.1 year) and 42 Caucasian children (21 male/21 female, 9.7 +/- 1.2 year). Pima Indian children were taller (p < 0.001), heavier (p < 0.001), and fatter (p < 0.0001) than Caucasian children. Absolute values of RMR were higher in the Pimas than in the Caucasians (p < 0.001), but were similar when adjusted for differences in body size, body composition, and sex. In Pima Indian girls before puberty (< 10 years; n = 8), adjusted values of RMR were negatively correlated with the mean body mass index (BMI) of the parents (r = -0.88; p < 0.005). Inasmuch as resting metabolic rate was not low in Pima children, the data suggest that the major factors in the weight gain of 10-year-old Pima children may be reduced physical activity and/or excess energy intake. However, this study does not exclude the possibility that a low metabolic rate may be a predisposing factor at an earlier age. PMID- 8357499 TI - Impact of experimental manipulation of energy intake and expenditure on body composition. AB - There is persuasive evidence that much obesity is due to underexercising rather than overeating. In a series of randomized, controlled trials we found that sedentary men who take up jogging lose body fat in proportion to miles run, increase their energy intake, and improve their lipoprotein pattern. In a 1-year comparison of fat loss by dieting vs. fat loss by exercise without dieting, both methods were found to be effective in moderately overweight men, and both approaches raised plasma HDL cholesterol. We also demonstrated in overweight men and women losing weight on a prudent diet (low fat, low cholesterol) that adding exercise to energy restriction further increased loss of body fat and reduced waist-to-hip girth ratio, especially in men. Risk of coronary heart disease was also substantially further reduced by addition of exercise, in both sexes. These studies suggest that regular exercise is a valuable addition to dietary change for weight control and reduction of risk of chronic disease in people of all ages. In this article I shall describe studies done by our group in the past 10 years to investigate the effects of varying energy expenditures and varying caloric intakes on body composition, in particular body fat content. The intervention studies are of relatively long duration (1 or 2 years) and have been conducted in free-living men and women. Such long-term investigations are rare in children and adolescents. Although experience in adults cannot be translated directly to children, our findings may indicate profitable research directions for future obesity research in the young.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357500 TI - Trends in body composition for infants and children in the U.S. AB - Nationally representative health examination surveys have collected anthropometric measurements on children and adolescents in the U.S. These data may serve as very crude indicators of total fat or fat-free body mass, but do not yield information on body composition per se. Attempts to accurately describe trends in obesity for children and adolescents have been complicated by a number of limitations associated with body measurements taken over time in sequential surveys. Inferences from limited anthropometric measures should be made cautiously. Factors to consider include the selection of cutpoints for trend analysis, changes that may be within range of technical measurement error, and use of data at extreme percentiles. Ostensible trends may be genuine, but they may also be influenced by methodological differences across surveys. Comparative data are presented for selected body measures from 1963 to 1980 for U.S. children and adolescents sampled in national health examination surveys, and apparent differences are discussed. PMID- 8357501 TI - Ethnic variation in the prevalence of obesity in North American children and youth. AB - The estimated prevalence of obesity in North American children and youth (6 to 17 years) in the 1960s through the 1980s is reported. Use of the triceps skinfold and BMI independently and in combination as indicators of obesity provides different estimates of prevalence due to ethnicity. With the triceps skinfold as the indicator, there is an increase in the prevalence of obesity and a reduction in variation between Black and White children and youth from the 1960s to 1980; however, with the BMI as the indicator, there is no change in the prevalence of obesity and negligible ethnic difference in these national data sets. On the other hand, the prevalence of obesity has increased over time in Mexican American and American Indian children and youth. Data for American children and youth of Asiatic ancestry are limited. PMID- 8357502 TI - Obesity and cardiovascular disease risk factors in prepubescent and pubescent black and white females. AB - A total of 2379 females equally divided between black and white were enrolled at 9 or 10 years of age. Participants were seen yearly for 5 years for a complete medical examination, evaluation of socioeconomic status, and patterns of eating and physical activity. Parents were seen in year 1 and responded to a questionnaire in years 3 and 5. At baseline, black females 9 to 10 years of age were taller and heavier and had greater BMI and skinfold thickness than white females. On the basis of dietary history, black females consumed more total energy and more calories as fat than white females. White females were physically more active and spent less time than black females watching television. More black than white females expressed a desire to be on the fat side, and black mothers were noted to be 20 lb. heavier than white mothers. PMID- 8357503 TI - Epidemiology of physical activity and fitness in children and adolescents. AB - Variations in physical activity and aerobic power are examined in relation to age and gender of children and adolescents. Reviews of the world literature show aerobic power relative to body mass remains stable from ages 6 to 16 for males, but for females it declines about 2% per year. Overall, males are about 25% more fit than females. Reviews of nine studies using standardized self-reports or objective measures of physical activity revealed that males are about 15 to 25% more active than females. Over the school age years, a consistent decline in physical activity is seen, with males decreasing about 2.7% per year and females decreasing about 7.4% per year. These data suggest that older youth and females are at increased risk of obesity because of a sedentary lifestyle. PMID- 8357504 TI - Trends and patterns in height and weight status of low-income U.S. children. AB - To better define the trends and patterns of growth for low-income children, we studied the anthropometry data collected by the second National Health and Nutrition Examination Survey (NHANES II) and the CDC Pediatric Nutrition Surveillance System (PNSS). Based on NHANES II, we found that low-income children appear to have a greater prevalence of shortness (low height-for-age), but do not have a greater prevalence of overweight (high weight-for-height) when compared with children from higher income families. Based on 12 states that were monitored continuously by the PNSS from 1980 to 1989, low-income children under 5 years of age appear to have a stable trend of height and weight status, with the exception of Asian children, most of whom were from Southeast Asian refugee background, showed a dramatic improvement in height status. However, based on PNSS data for the years 1977 to 1990 from Louisiana and Michigan, school-aged children and adolescents appear to have become slightly taller as well as having significant increases in body weight in relation to height. An additional investigation is needed to verify this trend of increasing excess weight among older, low-income children. PMID- 8357505 TI - Does childhood obesity track into adulthood? AB - Between 1971 and 1981 the Muscatine Coronary Risk Factor Project measured, in six biennial school surveys, 2631 schoolchildren 9 to 18 years of age. Beginning in 1981, these individuals were measured near their 23rd, 28th, and 33rd birthday. This article examines the tracking from childhood into young adult years of the heights, weights, body mass indices (BMI), and triceps skinfold thicknesses (TSF) of these individuals. Depending on age and gender, tracking correlations for height ranged from 0.41 to 0.97; for weight they ranged from 0.51 to 0.88; for BMI they ranged from 0.58 to 0.91; and for TSF they ranged from 0.26 to 0.58. From 49 to 70% of children in the upper quintile of weight were found in the upper quintile of weight as adults, from 48 to 75% of children in the upper quintile of BMI were again in the upper quintile as adults, and from 25 to 56% of children in the upper quintile of TSF were again in the upper quintile as adults. These measures track from childhood into young adult life, and the majority of obese children become obese adults. However, about 31% of children from the upper quintile of BMI became adults with substantially lower levels, while a similar number of lean children become obese adults. Why some obese children become obese adults and others do not remains an unanswered question. The data presented herein indicate that obesity is often acquired during childhood and adolescence when preventive measures could be applied. PMID- 8357506 TI - A review of the impact of fluoride on adult caries. PMID- 8357507 TI - Development and verification of the proximal/marginal plaque index. AB - The purpose of this study was to compare the ability of experienced and newly trained investigators to use the published Global Plaque Index and a newly developed Proximal/Marginal Index (PMI) that focuses on disclosed plaque at clearly defined proximal and marginal surfaces. Four independent clinical studies were performed, two with each index, on 11 subjects per study. In each study, examinations were conducted before and after brushing, to determine inter- and intra-examiner comparisons over a range of plaque levels. Inter-examiner reliability estimates for the PMI were at a level below Global Plaque index means. Intra-examiner agreement values were similar for both indices. Both scoring systems are considered sufficiently validated to detect product differences in clinical studies. PMID- 8357508 TI - Clinical plaque removal efficacy of three toothbrushes. AB - A single-blind, randomized clinical study compared plaque removal efficacy of three toothbrush designs under conditions simulating normal use. Ninety (90) subjects with substantially complete dentition used one of the three toothbrushes: Advanced Design Reach, Crest Complete and Oral-B 40. Subjects were examined for plaque before and after a single brushing using the Global Plaque Index to estimate plaque on the entire tooth surface, and the Proximal/Marginal Plaque Index (PMI), a new index, was used to estimate plaque at proximal and marginal surfaces of the teeth. The Advanced Design Reach toothbrush reduced plaque scores significantly more than did the other toothbrushes tested (p < 0.05) using either scoring method. At marginal and proximal sites, combined or separate, Advanced Design Reach toothbrush was significantly more effective than the other toothbrushes in plaque removal and produced significantly more plaque free sites than the other two toothbrushes. Evaluation of all anterior and posterior parts of the dentition with the Global Plaque Index indicated that Advanced Design Reach was superior in removing plaque in these regions. Both plaque indices were highly correlated (correlation coefficient 0.91) indicating excellent consistency by the dental examiner. PMID- 8357509 TI - Plaque removal efficacy of two children's toothbrushes: a one-month study. AB - Reach Wonder Grip toothbrush for children was evaluated for plaque removal efficacy and compared to the Colgate Plus Junior (extra soft). The subjects appeared at the test site with overnight (14-18 hours) plaque accumulation. After qualifying for the study, sixty-eight (68) subjects were randomly assigned one of the test brushes. They then participated in the test evaluation at the clinical site wherein plaque levels were measured before and after a one minute brushing. Plaque removal efficacy was evaluated by the Global Plaque Index (percent of tooth surface covered by stained deposit). The subjects then used the assigned toothbrush at home for one month and returned to the test site to repeat the baseline evaluations. After their final plaque evaluations, the subjects were given a new toothbrush from each brand to use at home for one week and the subject and the parent were asked to complete a preference questionnaire. Sixty seven (67) subjects completed the one month study. After one month's use of twice per day brushing, neither of the test toothbrushes demonstrated any evidence of oral irritation that could be related to toothbrushing. The results indicated that Reach Wonder Grip for Children was significantly more effective (p < 0.05) than Colgate Plus Junior in removing overall (Global) plaque at the initial exam period. The preference questionnaire indicated that the Reach Wonder Grip toothbrush was preferred by both the children and their parents. It is concluded that the new Reach Wonder Grip toothbrush for children is safe and effective for plaque removal. PMID- 8357510 TI - Second malignancies after chemotherapy and transplantation. PMID- 8357511 TI - Current advances in the treatment of gastrointestinal malignancy. PMID- 8357512 TI - Macrophage function activating cytokines: potential clinical application. PMID- 8357513 TI - Recent advances in diagnosis of hemoglobinopathies. PMID- 8357514 TI - [Brainstem auditory evoked potentials in low and high risk newborns]. AB - Brainstem auditory evoked potentials (BAEP) were performed in a population of preterm infants of 32-34, 35-37 and 38-41 weeks of gestational age (GE) high risk newborns, and in 38-41 weeks GE low risk newborns. Statistical differences were found between both 38-41 weeks GE groups. High risk newborns showed longer latencies of waves III and V (P < 0.001), and I-III and I-V interwave intervals (P < 0.01). Our data show that auditory brainstem system suffer in high risk newborns. Results is discussed in relationship with other brainstem auditory evoked potentials studies in high risk newborns due it's clinical implications of present data. PMID- 8357515 TI - [Child abuse: a disturbing problem]. AB - This current information on "battered child syndrome" (BCS) was obtained during 1990 from nine institutions in Tijuana, Baja California; 549 cases of BCS were studied, of which 338 were female, 203 male, eight of indeterminate sex due to loss documentation. Child abuse was manifested in all its forms: beatings, sexual abuse, neglect, and affective indifference. The victim's and perpetrator's characters were analyzed together with other factors which had to be taken into consideration in order to detect results which were similarly described in the literature. It is of utmost importance to alert all medical staff to this terrible social problem for the complete treatment of the affected child and the family environment. Community support, and legislation to adequately cover rights of minors and their protection are imperative to elimination of the battered child syndrome. PMID- 8357516 TI - [Pharyngo-tonsillitis and necrosing submaxillary adenitis caused by Streptococcus pyogenes associated with toxic shock syndrome in children from Mexico City]. AB - We report on six previously healthy children between nine months and nine years old, who suffered streptococcal faringoamigdalitis and cervical adenitis with scarlet fever and toxic shock syndrome; four of them died in a fulminant course and two survived. These patients behave similarly to others reported from United States of America, England and Australia, and in similar way these clinical entity could be due to bacterial pyrogenic exotoxins according to the clinical fulminant course. PMID- 8357517 TI - [Neonatal conjunctivitis caused by Chlamydia trachomatis]. AB - 32 newborns with neonatal Chlamydia trachomatis conjunctivitis were reported. Diagnosis was carried out through immunofluorescent monoclonal antibody of conjunctiva scraping staining; 37 conjunctiva samples were taken from same number of newborn patients not responds to topical antibiotic treatment. The sample came out from two different third level institutions with maternal facilities and attending more than five thousand deliveries per year each one of them. Were studied incidence and clinical picture from neonatal C. trachomatis conjunctivitis. Positive immunofluorescent and conjunctive culture of secretion to C. trachomatis in the sample were 86 per cent (32 out of 37). 19 of the newborns acquired Staphylococcus associated to C. trachomatis (59%): nine with S. aureus in six Staphylococcus negative coagulase was isolated and four with the latest two. Out of 32 patients who demonstrated positive cultures to C. trachomatis (86%), 22(69%) were males and ten (31%) were females. Significant proportion of newborns were identified as small for gestational age. 18 of them were born by natural way and 14 by cesarean section. In 16/32 (50%) had interstitial pneumonia by Chlamydia. The main clinical findings were stated as: conjunctiva exudate in different stages including purulent secretion and oedema or inflammation of the ophthalmic conjunctiva. Those newborns where topical therapy did not irradiate the organism and demonstrated clinical picture persistence or relapse and diagnosis of C. trachomatis infection, systemic treatment with erythromycin and topic tetracycline were installed, disappearing all symptoms. Maternal history related to neonatal disease were mainly: endocervical infection, miscarriages and or preterm delivery. PMID- 8357518 TI - [Validity of a scale of vital prognosis in multiorgan failure syndrome: experience at a pediatric ICU]. AB - In order to evaluate the utility of modified score index for multiple organ failure syndrome (MOFS) detection, we studied 31 critically ill pediatric patients at University Hospital of Puebla. They had a critical illness and they were successfully animated and developed two or more organ failure other than initial lesion. Were calculated sensibility, specificity, positive predictive value and negative predictive value of clinical and biochemical criterion of modified score index and results were few consistent. Were assessed that scale for know its predictive value and results were significant: sensitivity 81%, specificity 30% and accuracy, 54.5%. Finally we recommended caution to use anyone score system in evaluating MOFS. PMID- 8357519 TI - [Changes in the consciousness as a manifestation of intestinal intussusception]. AB - Many reviews have included the salient features of the clinical spectrum of intussusception: abdominal pain, vomiting, bloody stools and abdominal mass. We report a case with atypical presentation of the illness, presenting as altered consciousness. A misdiagnosis and delay of treatment is often associated with increased morbidity. Either plain radiographs, supplemented by ultrasonography of the abdomen, or a barium enema should be performed in infants with unexplained lethargy. PMID- 8357520 TI - [Hereditary blepharophimosis with visual alterations]. AB - We report a Mexican family with two members (mother and daughter) affected with blepharophimosis hereditary syndrome: ptosis of the eyelids, blepharospasm and epicanthus inversus. The daughter presented: hyperopia, astigmatism, hemispheric asymmetry, superficial mental deficiency and ovarian cyst. The mother with ophthalmological affectation, present too border line intellectual quotient. Clinical findings in this family illustrate autosomal dominant trait; differential diagnosis should be taken into account for genetic counselling. PMID- 8357521 TI - [Funicular torsion with testicular necrosis in the newborn]. AB - Three cases of extravaginal torsion of the spermatic cord with infarct of the testicle in the newborn are presented. All three cases had acute fetal distress. They had in common being the products of multiparous women, born in a distocic fashion with a prolonged labor without prenatal control. One of the had a shoulder impaction with required forceps use. Two of them were delivered on vaginal way and the other one by cesarean section. In all three cases, torsion was present at birth. Diagnosis was made between third and fifth day of life; the clinical findings were: enlargement of the right scrotal bag, purple discoloration of the skin, a painless hard mass that did not permit the passage of light (transillumination) and the absence of cremasteric reflex. A right resolution ultrasound was useful in determining the inflammatory tumoral mass. A right orchidectomy and pexy of the contralateral testicle were done in the three cases with nonabsorbable sutures and no testicular implants. The following diagnoses should be discarded prior to a definitive diagnosis: scrotal edemas, hydrohematocele, strangled inguinal hernia with infarct and testicular neoplasia. PMID- 8357522 TI - [Alport's syndrome: new findings]. AB - The Alport's syndrome is a disease characterized by a symptomatic triad: nephropathy, hypoacusia and ocular alterations. This syndrome is genetically heterogeneous and results from numerous mutations in COL4A5 gene, whose locus resides on the long arm of the X chromosome (Xq22). This gene codifies for IV collagen alpha 5 chain, which is a fundamental constituent of the glomerular, lens and Corti's organ basal membranes. Present knowledge on molecular genetics and the characterization of the different mutations that affect the Alport's gene will lead to classification of this syndrome in subtypes, according to those mutations, and to its phenotypic expressions; in addition, some syndromes, phenotypically similar, will probably have to be distinguished from Alport's disease, in a future, if a genetic alteration is found in genes other than COL4A5. PMID- 8357523 TI - Gordon James Mogenson (1931-1991). PMID- 8357524 TI - A special issue dedicated to Gordon James Mogenson (1931-1991). PMID- 8357525 TI - Bibliography of Dr. Gordon J. Mogenson. PMID- 8357526 TI - Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of D-amphetamine. AB - The experiments reported here have investigated the impact on reward-related processes of lesioning the basolateral amygdala, ventral subiculum and prelimbic cortex which represent the major limbic sources of afferents to the ventral striatum. The results showed that, while lesions of the prelimbic cortex were without effect on the approach to a CS predictive of sucrose reinforcement and the acquisition of a new response with conditioned reinforcement, lesions of the other two structures significantly impaired both responses. However, there were important differences between the effects of basolateral amygdala and ventral subiculum lesions. Thus, lesions of the ventral subiculum completely abolished the locomotor response to intra-accumbens infusions of D-amphetamine, in addition to blocking the potentiative effect of the same treatment on responding with conditioned reinforcement. Lesions of the basolateral amygdala, by contrast, reduced the control over behaviour by a conditioned reinforcer, but not the potentiation of that control by intra-accumbens D-amphetamine except at the highest dose. Moreover, the locomotor response to D-amphetamine-induced increases in dopamine in the nucleus accumbens was unaffected by amygdala lesions over the dose range blocked by ventral subiculum lesions. The results suggest a rather selective effect of amygdala-ventral striatal interactions on processes subserving conditioned reinforcement and a more fundamental influence of ventral subiculum-ventral striatal interactions in mediating the psychomotor stimulant effects of D-amphetamine. PMID- 8357527 TI - Relationship between schedule-induced polydipsia and amphetamine intravenous self administration. Individual differences and role of experience. AB - It has been suggested that drug abuse belongs to a larger class of addictive behaviors, including smoking, eating or gambling, which are mediated by common processes. Since laboratory animals can be induced to develop drug self administration as well as indulge in compulsive eating or drinking, the present experiments were designed to find out if the same animals were susceptible to both behaviors. Only certain rats develop amphetamine intravenous self administration (SA), and this susceptibility can be predicted from their enhanced locomotor response in a novel environment. Furthermore, excessive, non-regulatory drinking, referred to as schedule-induced polydipsia (SIP), in response to the periodic delivery of small amounts of food is only observed in certain rats. Since the propensity to SA has been shown to be influenced by experimental factors and testing for SIP was found to modify behavioral and biological parameters related to the propensity for drug-seeking, we also investigated whether experience of SIP influenced the subsequent development of SA. In Expt. 1, the rats that developed SA also acquired SIP, and had a higher locomotor response to novelty. The results of Expt. 2 showed that testing for SIP influenced the predisposition to develop amphetamine SA. When animals were tested for SIP first, the polydipsic rats subsequently failed to acquire SA, and had a reduced locomotor response to novelty. These changes seemed to be specific to the experience of SIP, as individual differences in the locomotor response to novelty were unchanged when animals were housed in standard laboratory conditions over a period of one month between the two tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357528 TI - Effects of repeated amphetamine injections on lateral hypothalamic brain stimulation reward and subsequent locomotion. AB - Intracranial self-stimulation was assessed by the curve-shift method before and after D-amphetamine (1 mg/kg, i.p.) or vehicle injections given 8 times at 48-h intervals. Locomotor was assessed, in a separate test box, for the hour following the 35-min self-stimulation sessions. Amphetamine facilitated self-stimulation, shifting to the left the function relating response rate to stimulation frequency. The drug was most effective the first time it was given; the effects were weaker but unchanging across the remaining 7 days of repeated testing. When control animals that had been given vehicle for the eight initial days of testing were subsequently treated with amphetamine, it facilitated the behavior to the same extent as was seen the first time it was given in the experimental group. Amphetamine significantly increased locomotion in the period following the self stimulation tests, and the degree of increase grew slightly but steadily with repeated testing; there was more rapid sensitization to this response in animals that were not subjected to self-stimulation testing prior to activity testing. These data do not fit well with earlier reports of sensitization to the reward enhancing effects of amphetamine and reflect a potential dissociation between the locomotor-stimulating and reward-facilitating effects of amphetamine. PMID- 8357529 TI - Cholecystokinin-dopamine interactions within the nucleus accumbens in the control over behaviour by conditioned reinforcement. AB - Cholecystokinin (CCK) is colocalised with dopamine in the postero-medial nucleus accumbens (NAS). We have utilised an acquisition of a new response procedure to investigate the interaction between CCK and dopamine in the control over behaviour by conditioned reinforcers. A conditioned reinforcer (CR) may be defined as an initially neutral stimulus which gains control over behaviour through selective association with a primary reinforcer. Here, rats learned to associate a light/noise compound stimulus with the imminent availability of 10% sucrose reinforcement. Later, in the absence of sucrose, responding on one of two novel levers (the CR lever) was acquired and maintained by contingent presentation of the CR alone, while responding on the second lever had no programmed consequences. In Expt. 1, infusion of 10 micrograms D-amphetamine within the postero-medial NAS enhanced responding selectively on the CR lever. Infusion of sulphated CCK octapeptide (CCK: 1 or 10 ng) alone within the same area had no effect on response rate. However, infusion of CCK immediately prior to D-amphetamine caused a dose-dependent potentiation of the impact of D amphetamine upon rates of response on the CR lever. In Expt. 2, infusion of D amphetamine (10 micrograms) within the postero-medial NAS again enhanced responding selectively upon the CR lever. Intra-accumbens infusion of CCK (10 ng), or s.c. administration of the CCKA receptor antagonist devazepide had no effect upon response rates. However, CCK again potentiated the D-amphetamine induced increase in rates of response, and this potentiation was blocked by pretreatment with devazepide. These results are discussed in terms of the co modulation by CCK and dopamine of the processing of reward-related stimuli within the NAS. PMID- 8357530 TI - Acquisition of a spatial conditioned place preference is impaired by amygdala lesions and improved by fornix lesions. AB - This experiment examined the role of the lateral nucleus of the amygdala, the hippocampus and the dorsal striatum in the acquisition of a conditioned place preference (CPP). The CPP was established on a radial maze which was rotated before each daily trial so that only distal cues could be used to distinguish among locations on it. Each rat was assigned a paired location in which the arm contained food, and an unpaired location in which the arm was empty. A training trial consisted of 30-min confinements in the paired and unpaired locations on successive days. Groups of animals received between 1 and 4 training trials, after which they were tested for their preference between their two assigned locations with no food in either one. Normal animals acquired a CPP after 4 training trials, an instance of stimulus--reward learning. Electrolytic and neurotoxic lesions of the lateral nucleus of the amygdala prevented acquisition of the CPP in 4 training trials, suggesting that some function of this structure (or of a neural system that includes it) is required for acquisition and/or expression of stimulus--reward associations. Striatal lesions had no effect on the CPP. Fornix lesions facilitated acquisition of the CPP after 1-3 training trials, but no CPP was observed in animals with combined fornix and amygdala lesions, suggesting that exposure to the maze environment led to the processing of information in a hippocampal system that interfered with acquisition or expression of the amygdala-based CPP. Fornix lesions also increased the number of entries into maze arms on the test day, and concurrent amygdala lesions attenuated this increase. This finding suggests that the increase in arm entries may have been generated by the amygdala and suppressed by the hippocampus. Arm entries were interpreted as an instance of a particular type of exploratory behavior. Therefore, the present results suggest that a neural system including the lateral nucleus of the amygdala mediates both stimulus--reward learning and at least one form of exploration, possibly through its connections with the motor output system in ventral striatum. A hippocampal system appears to suppress or interfere with both of these behaviors in normal animals. PMID- 8357531 TI - Two types of motivation revealed by ibotenic acid nucleus accumbens lesions: dissociation of food carrying and hoarding and the role of primary and incentive motivation. AB - Rats with dopamine-depleting lesions of the nucleus accumbens (NAcc) no longer carry food and leave it in a refuge (carry-to-leave or hoard). The present study replicates this finding and extends it to rats with ibotenic acid lesions. The same rats, however, were found to carry food to a refuge to eat it (carry-to eat). Thus, within a test session, control rats would first carry food to eat it, and when sated, carry the remaining food to leave it in the refuge. NAcc food deprived rats carried food to eat it but when sated engaged mainly in exploratory behavior. When carrying-to-eat, NAcc rats modulated responses normally to food size and eating time, their movement speed and motor patterns were normal, and their eating times were normal. Nevertheless, they were slower to return for food after eating, and they did not show normal slowing of eating times with successively presented food pellets. The failure of NAcc rats to carry-to-leave when sated was not related to general inactivity. In activity tests, they were as active in the light, more active in the dark, and did not differ from control rats under amphetamine (1.25 and 2.5 mg/kg). Their impairments were also not related to damage to other forebrain related structures, as they displayed normal neocortical and hippocampal atropine-sensitive and atropine-resistant electroencephalograms (EEG). The finding that NAcc rats carry-to-eat when hungry but do not carry-to-leave when sated suggests two separate conclusions. First, food carrying can be dissociated into two separate actions with respect to neural control, carrying-to-eat and carrying-to-leave. Second, the selective involvement of the NAcc in only carrying-to-leave suggests that it is associated with recruiting actions in response to the secondary incentive features of food but is not required for behaviors associated with food consumption. Other structures are presumably activated by the primary drive-reducing features of food. The results are discussed in relation to two-factor theories of motivation. PMID- 8357532 TI - Microbial metabolism of quinoline and related compounds. XVIII. Purification and some properties of the molybdenum- and iron-containing quinaldic acid 4 oxidoreductase from Serratia marcescens 2CC-1. AB - Serratia marcecens 2CC-1 utilizes quinaldic acid (quinoline 2-carboxylic acid) as sole source of carbon, nitrogen and energy. Growth of strain 2CC-1 on quinaldic acid as well as on nicotinic acid and hypoxanthine was inhibited completely by the molybdate antagonist tungstate, whereas growth on kynurenic acid and 6 hydroxynicotinic acid was not affected by tungstate. The synthesis of the molybdenum-containing hydroxylases quinaldic acid 4-oxidoreductase and nicotinic acid 6-oxidoreductase was found to be inducible. In addition, Serratia marcescens 2CC-1 produced a constitutively expressed xanthine oxidoreductase. Quinaldic acid 4-oxidoreductase was purified 1075-fold with a recovery of 5%. For catalytic activity, artificial electron acceptors were necessary. The 95-100-kDa enzyme was a heterodimer with subunit molecular masses of 75-80 kDa and 18-19 kDa. Quinaldic acid 4-oxidoreductase contained 2.3-3.7 g atom of iron and 0.5-0.6 g atom of molybdenum per mol of enzyme. The absorption spectrum exhibited maxima at 280 nm, 334 nm, 480 nm and a shoulder at 550 nm, with A280/A334 = 4.8, A280/A450 = 10.0, A280/A480 = 9.4, and A450/A550 = 1.6, suggesting the absence of a flavin cofactor. Acridine, quinacrine, ethylenediaminetetraacetate, 2,2'-dipyridyl, 1,10 phenanthroline and iodoacetate did not affect enzyme activity. p Hydroxymercuribenzoate, m-arsenite, cyanide and methanol were effective inhibitors of quinaldic acid 4-oxidoreductase. Cyanide-inhibited enzyme was reactivated by treatment with S2-, indicating the presence of a pterin molybdenum cofactor with a monooxo-monosulfidotype molybdenum center. Quinaldic acid 4 oxidoreductase showed a very high substrate specificity, quinaldic acid being the only substrate found to be transformed significantly. PMID- 8357533 TI - Isolation and characterization of a new ribosomal protein from the thermophilic eubacteria, Thermus thermophilus, T. aquaticus and T. flavus. AB - A ribosomal protein, showing no homology with other known prokaryotic ribosomal proteins, was isolated and characterized from the thermophilic eubacteria, Thermus thermophilus, T. aquaticus and T. flavus. This small (26 amino acids) and strongly basic (1 acidic and 13 basic residues) protein displayed the same primary structure from all three sources. Interestingly, it shows about 65% homology with a ribosomal protein from spinach chloroplasts (J. Schmidt, personal communication). PMID- 8357534 TI - The isoforms of human neutrophil elastase and cathepsin G differ in their carbohydrate side chain structures. AB - The two proteinases found in human neutrophil granules, elastase and cathepsin G, each are normally isolated as a mixture of isoforms differing only in carbohydrate content. Elastase has two N-glycosylation sites occupied (Asn-45 and Asn-144), whereas cathepsin G has only one (Asn-64). Analysis of a minor form of elastase (E-1) and cathepsin G (C-1) indicates that the carbohydrate structures at each glycosylation site are complex-type bi-antennary chains usually associated with secretory glycoproteins. In contrast, the isoforms E-3 and C-3, the major forms of elastase and cathepsin G respectively, contain exclusively truncated, oligomannose-type chains at the same positions in the sequence of each protein. These data suggest the possibility that certain elastase and cathepsin G isoforms (E-1 and C-1) might be destined for secretory, others (E-3 and C-3) for lysosomal functions. PMID- 8357535 TI - Limited proteolysis of chloroplast glyceraldehyde-3-phosphate dehydrogenase (NADP) from Spinacia oleracea. AB - The structural and functional properties of chloroplast glyceraldehyde-3-P dehydrogenase I (D-Glyceraldehyde-3-phosphate: NADP oxidoreductase (phosphorylating) EC 1.2.1.13) from Spinacia oleracea were investigated by limited proteolysis. The enzyme is insensitive to trypsin and chymotrypsin, while Staphylococcus aureus V8 protease cleaves the C-terminal region of its subunits. Subunit A (36 kDa) is only partially cleaved at Glu 317. No intact subunit B (39 kDa) is found at the end of the proteolytic experiment: two forms are originated from this subunit which is cleaved at Glu 342 and Glu 320. Proteolytic cleavage at these sites does not significantly alter enzymatic activity, but leads to destabilization of the protein. Unlike the intact parent enzyme (600 kDa) the cleaved enzyme behaves as a 150-kDa species in size exclusion chromatography. PMID- 8357536 TI - Specific interactions of the allosteric effector 2,3-bisphosphoglycerate with human hemoglobin--a difference FTIR study. AB - The specific interactions of 2,3-bisphosphoglycerate (BPG) with human deoxy hemoglobin (deoxy-HbA) are studied by difference FTIR spectroscopy. Due to these interaction effects the O2 affinity of the hemoglobins is regulated. In deoxy-HbA a NH+ ... -OOC hydrogen bond is formed between beta 82 Lys and the carboxylate group of BPG. The phosphate groups of BPG are completely deprotonated causing a strong electrostatic stress within the Hb molecule. The aminotermini (beta 1 Val) interact with the phosphate groups but no hydrogen bonds are formed. The interaction is limited to an electrostatic interaction between the NH3+ and the negatively charged phosphate group, i.e. only ionic bonds are built up. The histidines beta 2 and beta 143 of the two beta-chains form hydrogen bonds with the phosphates. To each phosphate two bonds are formed. These bonds polarize each other and hence only the polar structures NH+ ... -OP of the hydrogen bonds are realized. This follows since no protons are present at the BPG molecules. Thus, caused by the hydrogen bonds and the electrostatic interaction the conformation of HbA is changed by BPG in the way that the T-structure is favored and hence the affinity for oxygen is decreased. PMID- 8357537 TI - 8th conversation in biomolecular stereodynamics. June 22-26, 1993. Abstracts. PMID- 8357538 TI - Flexibility of DNA within transcriptionally active nucleosomes: analysis by circular dichroism measurements. AB - The conformational flexibility of DNA in transcriptionally active chromatin fractions has been estimated by circular dichroism spectroscopy analysis and was found to be restricted in the same fashion as in bulk chromatin. The observation is discussed in the context of different models of active chromatin organization. PMID- 8357539 TI - Dynamics of unfolded nucleosomal fiber. AB - The "rigidity" of chromatin fiber solenoidal structure in different states of condensation was evaluated with the help of gel-electrophoresis. A new property of the unfolded nucleosomal fiber-the capacity to condense with temperature-was demonstrated. These results together with our previously obtained data (W.A. Krajewski et al., Mol. Gen. Genet. 230, pp. 442-448, 1991; W.A. Krajewski et al., Ibid. 231, pp. 17-22, 1991) testify that changes in DNA linking number of transcriptionally active minichromosomes arise in vivo from alteration of nucleosomal solenoid parameters (i.e. from supernucleosomal level of chromatin organization), rather than from core histone modifications only or from increased flexibility of DNA within nucleosomes. PMID- 8357540 TI - Stereochemical effects of methylphosphonate in B- and Z-DNA helices: variation in hydrophobicity and effective widths of grooves. AB - Stereochemical effects of methylphosphonate (MP) in B-DNA and Z-DNA duplexes are studied through molecular mechanics approach. Duplexes of different lengths, tetramers, hexamers, dodecamers are examined to assess the interstrand and intrastrand electrostatic effects due to MPs vis-a-vis phosphates. A variety of models which include duplexes with alternating S-MP and R-MP, alternating phosphate and MP and, duplexes possessing MPs in only one of the strands, are examined by considering both the S- and R-stereoisomers. Majority of the calculations are performed with CG sequences to delineate factors responsible for the stability of B- and Z-DNA, as well as B-->Z-DNA transition under nonionic conditions. The results show that both B- and Z-DNA duplexes are energetically favoured in the presence of MP due to overwhelming reduction in intrastrand as well as interstrand electrostatic repulsive interactions. The effect is distinct in oligomers longer than tetramers. Comparison of energetics of MP B- and Z-DNA duplexes suggests that an oligodeoxynucleotide such as d(CG)6 with all phosphates replaced by MPs may favour equally both B- and Z-DNA conformations. The analysis further provides an estimate of electrostatic interactions, operating at the grooves under a variety of conditions. Several specific and localised effects due to S-MP and R-MP are seen at CG and GC steps in various B-DNA and Z-DNA models. S MP in B-DNA reduces the effective major groove width by nearly 3 A hence denying access to the functional groups of endonucleases thereby enhancing the resistance of MP-DNA to enzymatic digestion. Further, methyl groups of MP render the surface of the DNA helix to be significantly hydrophobic which may explain higher permeability of MP-DNA in membranes as well as its less soluble nature in aqueous media. PMID- 8357541 TI - Comparative study of thermostability and structure of close homologues--barnase and binase. AB - Parameters of heat denaturation and intrinsic fluorescence of barnase and its close homologue, binase in the pH region 2-6 have been determined. The barnase heat denaturation (pH 2.8-5.5) proceeds according to the "all-or-none" principle. Barnase denaturation temperature is lower than that of binase and this difference increases from 2.5 degrees C at pH 5 to 7 degrees C at pH 3. Enthalpy values of barnase and binase denaturation coincide only at pH 4.5-5.5, but as far as pH decreases the barnase denaturation enthalpy decreases significantly and in this respect it differs from binase. The fluorescence and CD techniques do not reveal any distinctions in the local environment of aromatic residues in the two proteins, and the obtained difference in the parameters of intrinsic fluorescence is due to fluorescence quenching of the barnase Trp94 by the His 18 residue, absent in binase. Secondary structures of both native and denaturated proteins also do not differ. Some differences in the barnase and binase electrostatic characteristics, revealed in the character of the dipole moments distribution, have been found. PMID- 8357542 TI - An exact description of five-membered ring configurations. I. Parameterization via an amplitude S, an angle gamma, the pseudorotation amplitude q and phase angle P, and the bond lengths. AB - A method is developed which exactly parameterizes the configurations of five membered rings. In addition to the five bond lengths, (bj), four other parameters are needed to describe completely all configurations of a three-dimensional figure with five sides. Two of these parameters are taken as the phase angle, P, and amplitude, q (A), introduced by Cremer and Pople (J. Am. Chem. Soc. 97, 1354 (1975)) which give exactly the displacements of the atoms in any five-membered ring from a special plane (the CP plane). For the two other parameters, a second amplitude, S (A), and an orientation angle, gamma (the upper case Greek letter "gamma"), are introduced. These two new parameters describe the "distortion" of the projection of the ring in the CP plane. gamma is the angle in the CP plane at which the projected ring is maximally "spread" or "stretched," where the stretch is a least squares measure of position along a line through the ring center. S measures the difference between maximum stretch (in direction gamma) and minimum stretch (in direction gamma +/- 90 degrees) such that S = 0 denotes maximum symmetry. Transformations from Cartesian coordinates to the new internal coordinates, and from the new internal coordinates to the Cartesian set, are exact inverse transformations. Fortran source codes MAKERING and BREAKRING for these transformations are available. The set of four parameters aids in direct comparisons of ring structures and in detailed numerical analyses of data. They also aid the systematic generation of all possible rings, useful for theoretical studies of ring conformation. To demonstrate the descriptive method, we have generated distributions of q, P, S, and gamma for furanose rings in the structures of 665 nucleosides determined by X-ray crystallography. PMID- 8357543 TI - Laser photofootprinting of d(C).d(G).d(G) intramolecular triplex. AB - Supercoiling-induced structural transition of the d(C24GC21).d(G21CG24) sequence in plasmid DNA in the presence of Mg2+ at neutral pH results in alterations of efficiencies of not only single-quantum (pyrimidine[6-4]pyrimidone adducts) but also two-quantum (alkali-sensitive lesions of dG residues) photomodifications of nucleoside residues within this sequence. The generation of both types of photoreactions was achieved by the application of high-intensity laser UV radiation (intensity approximately 10(11) W/m2, pulse duration approximately 10( 8) s, lambda = 266 nm) for irradiation of a plasmid DNA. The modification extent sufficient for analysis of photoreaction efficiency distributions along both strands of the insert (photofootprinting) was obtained by the action of a single nanosecond pulse of laser UV radiation. The pattern of a laser photofootprinting is consistent with the d(C).d(G).d(G) triplex formation in the presence of Mg2+ within the insert and shows some details of this triplex structure. PMID- 8357544 TI - Modeling study on the cleavage step of the self-splicing reaction in group I introns. AB - A three-dimensional model of the Tetrahymena thermophila group I intron is used to further explore the catalytic mechanism of the transphosphorylation reaction of the cleavage step. Based on the coordinates of the catalytic core model proposed by Michel and Westhof (Michel, F., Westhof, E. J. Mol. Biol. 216, 585 610 (1990)), we first converted their ligation step model into a model of the cleavage step by the substitution of several bases and the removal of helix P9. Next, an attempt to place a trigonal bipyramidal transition state model in the active site revealed that this modified model for the cleavage step could not accommodate the transition state due to insufficient space. A lowering of P1 helix relative to surrounding helices provided the additional space required. Simultaneously, it provided a better starting geometry to model the molecular contacts proposed by Pyle et al. (Pyle, A. M., Murphy, F. L., Cech, T. R. Nature 358, 123-128. (1992)), based on mutational studies involving the J8/7 segment. Two hydrated Mg2+ complexes were placed in the active site of the ribozyme model, using the crystal structure of the functionally similar Klenow fragment (Beese, L.S., Steitz, T.A. EMBO J. 10, 25-33 (1991)) as a guide. The presence of two metal ions in the active site of the intron differs from previous models, which incorporate one metal ion in the catalytic site to fulfill the postulated roles of Mg2+ in catalysis. The reaction profile is simulated based on a trigonal bipyramidal transition state, and the role of the hydrated Mg2+ complexes in catalysis is further explored using molecular orbital calculations. PMID- 8357545 TI - Counterion-type characteristic effects on intrinsic bending components of calf thymus DNA; hydrodynamic investigations. AB - This paper stresses structural differences in A.T clusters of the ammonium salt of calf thymus (ct) DNA (ctNH4DNA) and the respective sodium salt, ctNaDNA. Sequence mediated intrinsic helix bends of ctNaDNA, distributed along the molecule partially randomly and partially phased with the helix screw (accompanying paper), are enhanced in ctNH4DNA. Additionally, the number of the most strongly bent segments (of A-tract character) is raised in ctNH4DNA by a counterion mediated shift of the equilibrium between at least two local DNA conformations. Nevertheless, the apparent DNA elongation, induced by the abolition of a single apparent solenoid-related DNA tertiary structure component which generates a special intrinsic DNA bend, is the same for NH4DNA and NaDNA. These conclusions follow from two independent sets of experimental results: (1.) Titration viscometric measurements with ctNH4DNA as a function of the cation concentration in comparison to ctNaDNA (KER et al., JBSD 9,537 (1991)) and respective DNA conformational analyses. (2.) Quantitative viscometric analysis of DNA conformational changes on netropsin (Nt) interaction of ctNH4DNA at different temperatures and comparison with the respective data for ctNaDNA (KER et al., NAR 9,2335 (1981). PMID- 8357546 TI - The reliability and validity of two HIV-specific health-related Quality-of-Life measures: a preliminary analysis. AB - OBJECTIVE: To evaluate the reliability and validity of two HIV-specific Quality of-Life (QoL) questionnaires in a UK sample. METHOD: Subjects were 99 HIV seropositive gay men (23 were asymptomatic, 41 were asymptomatic, 35 had AIDS). QoL was measured using two HIV-specific QoL questionnaires. MEASURES: An adaptation of the Medical Outcomes Study questionnaire and a self-completion version of the Health-Related Quality-of-Life Questions. Affect was measured using the Hospital Anxiety and Depression (HAD) Scale. Disease measures included Centers for Disease Control and Prevention (CDC) stage, and CD4 and CD8 cell count. RESULTS: Both QoL instruments showed good internal reliability on all scales used. Many of the scales, particularly those related to physical health and functional performance, showed significant correlations with CD4 cell count and other measures of disease progression. Measures of physical health showed a deterioration in QoL as disease progressed from asymptomatic disease to AIDS. In contrast, most subscales purporting to measure psychological aspects of QoL did not correlate significantly with measures of disease progression, nor was there any difference between CDC stages. Subjects' global ratings of QoL were most strongly correlated with the HAD depression scale, although there were also significant correlations with most other QoL scales. CONCLUSION: This study provides further evidence for the reliability and validity of two HIV-specific QoL questionnaires in a wider range of disease stages than hitherto reported and raises issues relevant to the practical use of QoL scales in HIV disease. PMID- 8357547 TI - Development of AIDS in people with transfusion-acquired HIV infection. AB - OBJECTIVE: To determine the rate of development of AIDS, and the demographic and clinical cofactors for development of AIDS in a group of 117 people with transfusion-acquired HIV infection, who were infected between 1980 and 1985 in New South Wales, Australia. RESULTS: By December 1991, 67 (57%, 95% CI 48-66%) of the study subjects had developed AIDS. The estimated median time to development of AIDS was 7.2 years from the date of infection. There was no significant difference in median age at infection or sex between individuals who did and did not develop AIDS. The median time to development of AIDS was shorter in older individuals (median time to AIDS for age groups 13-39, 40-59 and > 59 was 7.8, 7.1 and 5.4 years, respectively; P = 0.20). A significantly greater proportion of individuals who had never received treatment with zidovudine developed AIDS compared with individuals who had (P = 0.04). But in a statistical analysis which took account of the changing availability of zidovudine over time, there was no significant association between the development of AIDS and treatment with zidovudine (P = 0.44). CONCLUSION: Consistent with other studies, age appeared to increase the rate of progression to AIDS, although not significantly so in this study. PMID- 8357548 TI - Pneumocystis carinii choroidopathy in AIDS patients. PMID- 8357549 TI - Liposomal amphotericin B for leishmaniasis treatment of AIDS patients unresponsive to antimonium compounds. PMID- 8357550 TI - Pyomyositis in patients with HIV infection. PMID- 8357551 TI - High triglyceride levels as a predictor of mortality in AIDS patients. PMID- 8357552 TI - Vertical transmission of hepatitis C virus and HIV. PMID- 8357553 TI - Comparison of eight commercial test kits for detecting anti-HIV antibodies in saliva specimens. PMID- 8357554 TI - HIV DNA and antibodies in syringes from injecting drug users: a comparison of detection techniques. AB - OBJECTIVE: Direct HIV testing of individual injecting drug users is not always feasible. As an alternative, we have evaluated the sensitivity and specificity of several techniques for detecting HIV-1-specific products in used syringes. DESIGN: Polymerase chain reaction (PCR) and antibody-capture assays were compared using syringes prepared with blood from HIV-1-positive and -negative individuals. METHODS: PCR sensitivity was maximized, enabling detection of single copies of HIV-1-specific proviral DNA. The limits of detection from used syringes were determined for PCR by diluting extracts and correlated to CD4+ cell counts. Similarly, limits of detection were determined for enzyme immunoassays (EIA) and Western blot. RESULTS: All techniques were highly specific, although with PCR false-positives were detected occasionally. EIA proved more sensitive than Western blot in detecting needles containing HIV-1-infected individuals' blood. Even after prolonged storage of syringes at room temperature, EIA was equal to or better than PCR as an HIV-1 detection technique. The most sensitive method for detecting HIV-1 was the viral-based EIA when the recommended predilution step was omitted. CONCLUSIONS: EIA proved preferable to PCR because of their higher sensitivity, absence of false-positives and easier sample preparation and analysis. PMID- 8357555 TI - A dose escalation study to determine the toxicity and maximally tolerated dose of foscarnet. AB - OBJECTIVE: To determine the maximum tolerated dose of intravenous foscarnet (trisodium phosphonoformate hexahydrate); and to examine antiviral activity at plasma levels shown to inhibit HIV-1. DESIGN: Dose escalation study in three male subjects with AIDS who received foscarnet by continuous intravenous infusion at a dose of 200 mg/kg per day, after a 20 mg/kg loading dose. The dose was increased until a plasma level > 150 micrograms/ml was attained. RESULTS: Foscarnet was discontinued due to progressive renal insufficiency in all three patients (days 11, 19, and 21). Renal function normalized in all three, and no adverse sequelae due to foscarnet were observed at 1 year of follow-up. A seizure was observed in one patient on day 19. Maximum daily doses of foscarnet achieved were 395 mg/kg, 389 mg/kg, and 523 mg/kg. No changes in serum Ca2+, Mg2+, or PO4- were observed. CONCLUSIONS: Renal effects and toxicity of foscarnet in evolving renal insufficiency is self-limiting and reversible when the drug is discontinued. Incremental increases in dose can result in rapid rises in the plasma level with renal failure and may be compounded by concomitant medications and underlying illnesses. PMID- 8357556 TI - Longitudinal study on the Quality of Life of symptomatic HIV-infected patients in a trial of zidovudine versus zidovudine and interferon-alpha. AB - OBJECTIVES: To compare the effect of treatment with zidovudine (ZDV) or a combination of ZDV and interferon-alpha (IFN-alpha) on patient Quality-of-Life (QoL); and to document changes over time in QoL. DESIGN: This study is part of a longitudinal, randomized, controlled clinical trial comparing the efficacy and tolerance of ZDV monotherapy and ZDV plus IFN-alpha. Patients were followed-up for 1 year. SETTING: Seven academic or general medical hospitals. PARTICIPANTS: Thirty-six symptomatic HIV-infected patients (Centers for Disease Control and Prevention stage IV) with a CD4+ count > or = 150 x 10(6)/l and Karnofsky Performance Status score > or = 60, who had not received ZDV or IFN-alpha before. METHODS: QoL was assessed using two self-report questionnaires (the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire and an AIDS-specific questionnaire), administered before and every 3 months after the start of the treatment. RESULTS: There were no significant differences in QoL between the two treatment groups over a 1-year period. Emotional, cognitive and social functioning improved in the entire group, and patients reported fewer symptoms (for example, shortness of breath, nausea and vomiting, influenza-like symptoms, diarrhoea, lack of appetite, taste disturbances, dizziness, weight loss, trouble in vision) and a better overall QoL until month 9. Thereafter, emotional, cognitive and social functioning and overall QoL deteriorated and patients reported more symptoms. Major complaints at baseline and follow-up were associated with fatigue and emotional functioning: patients reported a strong need to rest, and felt very tired, worried, tense and irritable. CONCLUSIONS: These results show that both treatments may have a temporary beneficial effect on patient QoL. QoL research may contribute to evaluation of clinical trials and provide patients with information about the effects of treatment on their QoL, thus enabling them to make informed decisions. PMID- 8357558 TI - A prospective study of vertical transmission of HIV-2 in Bissau, Guinea-Bissau. AB - OBJECTIVES: To determine the vertical transmission rate of HIV-2 and clinical findings associated with vertically transmitted HIV-2 infection. DESIGN: A prospective study of HIV-2 transmission in children of HIV-2-seropositive mothers, and a comparison of clinical findings between children of seropositive and seronegative mothers. SETTING: Recruitment of women delivering at the national hospital in Bissau, Guinea-Bissau. Follow-up by home visits. SUBJECTS AND METHODS: Eighty-six newborns of 82 HIV-2-seropositive mothers and a control group of 102 newborns of HIV-seronegative mothers were followed-up clinically and by HIV serology until the children reached the age of 20 months. RESULTS: Of the 86 children of seropositive mothers, 51 had a complete follow-up, 22 died and 13 were lost due to change of residence. Of the 102 children of seronegative mothers, 63 had a complete follow-up, 13 died and 26 were lost due to change of residence. None of 51 children of seropositive mothers had serological evidence of HIV-2 infection at the end of the follow-up period. There was no significant difference in the frequency of clinical symptoms between the children in the study group and the children in the control group. The mortality during the first year of life was not significantly different between the children of seropositive and seronegative mothers (13 out of 80 and 11 out of 94, respectively, P > 0.05, excluding children lost to follow-up). Only three of the dead children of seropositive mothers and one of the dead children of seronegative mothers had any symptoms that might be related to HIV-2 infection (diarrhoea > 1 month). CONCLUSION: Vertical transmission of HIV-2 appears to be rare. PMID- 8357557 TI - The impact of HIV on infectiousness of pulmonary tuberculosis: a community study in Zambia. AB - OBJECTIVE: To examine the impact of HIV on infectiousness of pulmonary tuberculosis (TB). DESIGN: A cross-sectional tuberculin survey carried out among household contacts of HIV-1-positive and negative patients with bacteriologically confirmed pulmonary TB. Contacts were also examined for active TB. SETTING: Index cases were recruited from patients attending the University Teaching Hospital in Lusaka, Zambia and household contacts were examined during visits to their homes within Lusaka. PATIENTS, PARTICIPANTS: A total of 207 contacts of 43 HIV-positive patients, and 141 contacts of 28 HIV-negative patients with pulmonary TB were examined. MAIN OUTCOME MEASURES: Proportion of contacts of HIV-positive and negative index cases with a positive tuberculin response (diameter of induration > or = 5 mm to a dose of 2 tuberculin units). RESULTS: Fifty-two per cent of contacts of HIV-positive pulmonary TB patients had a positive tuberculin response compared with 71% of contacts of HIV-negative patients (odds ratio, 0.43; 95% CI, 0.26-0.72; P < 0.001). This difference persisted after allowing for between household variations in the tuberculin response. Tuberculin response in the contact was related to age of contact, intimacy with the index case and crowding in the household. However, the effect of HIV status of the index case was not confounded by these variables. Tuberculin response in the contact was also related to the number of bacilli seen in the sputum smear of the index case which partially explained the effect of HIV status of the index case. Active TB was diagnosed in 4% of contacts of HIV-positive and 3% of contacts of HIV-negative cases, respectively (P = 0.8). CONCLUSIONS: HIV-positive patients with pulmonary TB may be less infectious than their HIV-negative counterparts and this may partly be explained by lower bacillary load in the sputum. PMID- 8357559 TI - Blood transfusion practices and blood-banking services in a Kenyan hospital. AB - OBJECTIVES: To identify ways to improve the operation of blood-screening programs and to decrease the inappropriate use of blood by evaluating blood-transfusion practices and blood-banking services in a Kenyan hospital. DESIGN: Prospective cohort. SETTING: The study was conducted in a rural district hospital in western Kenya between September 1990 and July 1991. METHODS: We collected data on all transfusion requests (blood donation, grouping, HIV screening) and blood recipients (age, sex, diagnosis, and for a 3-month period on the pediatric, maternity, and female wards, admission hemoglobin and outcome). RESULTS: During the 11-month study period, 799 patients received 927 transfusions: 67% were children < 15 years of age, 27% were adult women and 6% were adult men. Transfusions were often delayed due to reliance on patient-recruited donors. Patients who received blood donated on or after the date of request waited longer for transfusion (median, 3 days) than patients who received blood that had been banked and screened before the request (median, 1 day). Patient-recruited donors had a higher HIV-seropositivity rate than volunteer donors (13.4 and 4.6%, respectively; chi 2 test, P < 0.001). Overall, 47% of pediatric transfusions were classified as inappropriate: 23% did not meet the criteria of having hemoglobin < 5.0 g/dl and clinical evidence of respiratory distress, and 27% were transfused 2 or more days after requested. Among adults, 68% received one unit of blood or less. CONCLUSIONS: Improved laboratory services, reduction of unnecessary transfusions, and increased recruitment of volunteer donors are critical for improving the appropriate and timely use of blood and reducing transfusion associated HIV transmission. PMID- 8357560 TI - Townes-Brocks syndrome in an infant with translocation t (5;16). AB - We report the occurrence of Townes-Brocks syndrome (TBS) in an infant with a two break reciprocal translocation between chromosome 5 and chromosome 16. The occurrence of both abnormalities in the same subject could be due to chance. However, it is of interest to note that a familial case of TBS associated with an inv(16) with the same breakpoint at 16q12.1 has been reported. We suggest the possible disruption of the TBS gene at this breakpoint. PMID- 8357561 TI - The Noonan syndrome. The Nancy experience revisited. AB - 67 patients with Noonan syndrome seen over the last 29 years were selected preferentially on cardiac involvement. The cardiac anomalies consisted in the association of dysplastic pulmonary stenosis with asymmetric cardiomyopathy. In one patient, a translocation (3;22) was found. The relationship with cardio-facio cutaneous syndrome and with the group of phacomatoses is discussed. The familial occurrence (10 families) seems compatible with autosomal dominant inheritance. A gene location on chromosome 22 cannot be excluded. PMID- 8357562 TI - Twelve cases with hemihypertrophy: etiology and follow up. AB - Twelve patients with hemihypertrophy are described. All but one are sporadic cases. The parents were unrelated. Family and pregnancy histories are otherwise unremarkable in all cases. Diagnosis was always performed at birth or in the weeks following birth. There were 5 boys and 7 girls including one mother and her daughter. Hemihypertrophy was localized to the upper limb in one case and to the lower limb in one case. One patient had some features of Mc Cune Albright syndrome. Hemihypertrophy was associated with Silver-Russel syndrome in two patients. In all other cases hemihypertrophy was idiopathic. Mental and motor development were normal in all cases, as was puberty. During growth the body asymmetry was unchanged. Orthopedic problems complicated growth in some cases. The most obvious of these problems was scoliosis. Limb lengthening was necessary in 2 cases. One of our patients developed an abdominal tumor. One of our patients had two normal children. Hemihypertrophy is usually not inherited. However, the mother of one of our patients also had hemihypertrophy. PMID- 8357563 TI - Potter sequence due to renal aplasia and postaxial hexadactyly. A distinct entity? AB - Report on a prematurely born female with the Potter sequence, postaxial hexadactyly of both hands, and bilateral short metacarpals I. Autopsy findings included severely hypoplastic lungs, bilateral renal aplasia as well as aplasia of the vagina and uterus. Chromosomes were normal (46,XX). Similar--though not identical--observations have been published by Holzgreve et al. (5), by Bonnet et al. (2), and by Legius et al. (6). PMID- 8357565 TI - Nager acrofacial dysostosis and preaxial polydactyly: a further example with lethal outcome. AB - A sporadic malformed premature stillborn showing the typical craniofacial features of mandibulofacial dysostosis combined with unilateral extra thumb and visceral anomalies is described and classified as a preaxial acrofacial dysostosis of the Nager type (NAFD). Comparison with other rare similar cases reported in the literature is made and genetic heterogeneity discussed. PMID- 8357564 TI - Miller postaxial acrofacial dysostosis. The phenotypic changes with age. AB - We report data on the clinical and psychological follow-up of a boy with Miller postaxial acrofacial dysostosis syndrome between the ages of 1 and 7 years. After an initial psychomotor retardation intellectual and social function improved significantly after the use of hearing aids (50-70 db bilateral hearing loss). The facial appearance changed with age: the face became asymmetric and triangular with more pronounced ectropion and fine, thin lips. PMID- 8357566 TI - Mental retardation, ataxia, seizures, dysmorphia, and hydrocephaly in two sibs. Angelman syndrome or new syndrome. AB - We report two sibs with Angelman syndrome or an apparently new syndrome. In addition to severe mental retardation and seizures, clinical examination showed an ataxic and stiff legged gait, truncal hypotonia with hypertonia of the limbs, dysmorphic facial features (brachycephaly, large mouth, pointed chin and a prominent jaws) and scoliosis. Brain CT scan and MRI revealed ventricular enlargement and squared frontal horns. Pregnancy and delivery were uneventful. Karyotypes were normal. No deletion of chromosome 15q11-13 region was shown by molecular genetic techniques. The parents who are normal are second cousins. The condition is therefore probably inherited as an autosomal recessive one. PMID- 8357567 TI - The Larsen syndrome. The diagnostic contribution of the analysis of the metacarpophalangeal pattern profile. AB - In this report we illustrate the variable expression and the different modes of inheritance in Larsen syndrome. The important contribution of the metacarpophalangeal profile pattern analysis in the final diagnosis is emphasized. PMID- 8357568 TI - Characteristic facial dysmorphism, arachnodactyly and mental handicap in two unrelated girls: a distinct MCA/MR syndrome? AB - Two nonrelated, moderately mentally retarded girls are described with identical clinical signs and symptoms, i.e. brachycephaly, typical facies with thin lips and microstomia, ectomorphic habitus with extreme long, thin fingers and toes and hypoplastic external genitalia. The clinical findings in the present patients allow for the delineation of a new MCA/MR syndrome. PMID- 8357569 TI - Goldston syndrome reconsidered. AB - We describe two siblings with the combination of central nervous system malformations, renal dysplasia and hepatic ductal plate malformation. Based on the occurrence of a cerebellar Dandy-Walker malformation (variant), the diagnosis of Goldston syndrome was proposed in the first case. The second sibling however, showed a typical Meckel syndrome with occipital encephalocele. Both cases had a cranium bifidum with two defects in the squamous part of the occipital bone. This observation confirms that Goldston syndrome is not a distinct entity but merely a variant of Meckel syndrome, and that a cerebellar Dandy-Walker malformation can be a component of Meckel syndrome. PMID- 8357570 TI - Spire Corporation: a paradigm for success in the 90s. AB - There is much talk now of "defense conversion" and the need to turn a given country's "peace dividend" into improving its "infrastructure." Beyond the obvious political rhetoric, those terms bode well for the field of biotechnology. Every facet of technology must attend to its "delivery system," for the same obvious reason, roads and bridges must be maintained and improved. In the case of biosensors and their delivery into the human body, for example, it stands to reason that adequate focus should be paid to advancements in the field of the biomaterials from which they are made, or that house or carry them. PMID- 8357571 TI - Continuous non-diluted serum sample measurement with an ISFET glucose sensor. AB - An ion-sensitive field-effect transistor (ISFET) glucose sensor with a new membrane structure is fabricated and its characteristics are evaluated in continuous measurement of non-diluted serum glucose. This sensor chip is composed of two ISFETs and a gold electrode. An albumin-glutaraldehyde crosslinked membrane, patterned on one of the ISFET gates and the gold electrode, contacts an enzyme membrane deposited on the other gate in edge to edge. Making an electrical connection between the gold electrode and two ISFETs, this membrane enables stable sensor responses to be made. This sensor is mounted on a flow cell into which serum samples and air are alternately fed. The sensor output shows a good linear relationship, up to 300 mg dl-1 glucose, and correlates well with a conventional glucose analyzer. This sensor shows promise as a key device in the development of portable glucose monitors. PMID- 8357572 TI - An immunosensor for syphilis screening based on surface plasmon resonance. AB - In this paper the development of a surface plasmon resonance (SPR) immunosensor for syphilis screening is described. This immunosensor is based on the detection of antibodies in serum against the causative organism Treponema pallidum. In order to achieve selectivity a recombinant Treponema pallidum membrane protein A (TmpA) was used. This antigen can react with antibodies to T. pallidum, present in serum of syphilitic patients. Reproducible results have been obtained, using a 'sandwich SPR' method: binding of a sandwich antibody to the treponemal antibody after serum incubation was measured in real time while the binding was taking place. The SPR results obtained from ten blind-coded sera corresponded well with classical syphilis tests (Treponema pallidum haemagglutination assay (TPHA), fluorescent treponemal antibody-absorbed test (FTA-ABS), venereal diseases research laboratory flocculation test (VDRL) and TmpA-based enzyme-linked immunosorbent assay (TmpA-ELISA)). Preliminary experiments showed that direct measurement of serum (in the 'one step SPR') is not yet possible, probably as a result of non-uniformity of serum samples. The application of latex beads is considered to solve this problem. PMID- 8357573 TI - Non-leaking amperometric biosensors based on high-molecular ferrocene derivatives. AB - Poly(ethylene glycol)-bound ferrocene derivatives, synthesized after activation of ferrocene carboxylic acid with 1,1'-bis carbonyl diimidazol, are able to transfer electrons from the active site of reduced glucose oxidase to electrode surfaces. This opens a route to non-leaking mediated enzyme electrodes for the determination of glucose. PMID- 8357574 TI - The 3D structure of glucose oxidase from Aspergillus niger. Implications for the use of GOD as a biosensor enzyme. AB - The tertiary structure of glucose oxidase (GOD) from Aspergillus niger was determined by x-ray crystallography (to be described elsewhere). The overall folding of the enzyme is described with regard to its application in biosensors, and conclusions are drawn from experiments on electrical communication between the enzyme and the electrodes. PMID- 8357575 TI - Bienzyme strip-type glucose sensor. AB - A strip-type glucose biosensor, prepared using screen-printing technology and comprising glucose oxidase (E.C.1.1.3.4.), peroxidase (E.C.1.1.3.13.) and ferrocyanide as mediator incorporated into graphite-hydroxyethyl cellulose matrices is described. The sensor acted at 0.0 V vs Ag/AgCl electrode, and the response time was 50-60 s. The calibration was linear up to 25 mM of glucose. The sensor response was constant in the range of pH 7.0-8.5. At 25 degrees C the biosensor temperature coefficient was 2.7% degrees C(-1). The sensor was insensitive to a physiological level of ascorbic acid (40 microM) and was used for glucose determination in whole blood. PMID- 8357576 TI - Portable system for continuous ex vivo measurements of lactate. AB - The lactate profile in serum was monitored continuously in volunteers under physical exercise on a test bicycle. The assay was operated ex vivo by means of continuous sampling through a coaxial catheter. After dialysis online, lactate was converted by means of lactate oxidase immobilized to porous glass, and the depletion of oxygen was registered by means of a Clark electrode. Good agreement between the continuous monitoring and off-line analyses was found. PMID- 8357578 TI - Regulatory aspects of modified release dosage forms: clinical studies. AB - In a recently drafted "Note for guidance" of the European Community it is stated that "The therapeutic objective and rationale for developing the prolonged release product should be provided". This implies that any therapeutic claim should be documented by ad hoc clinical trials. Another "Note for guidance" describes "the studies to be conducted in man, which are specific to new extended release forms containing recognized active and safe medicinal substances so as to ensure a more prolonged action than the conventional pharmaceutical forms already marketed". From this second "Note for guidance" it appears clearly that three situations must be distinguished: a) a modified release dosage form is intended for use with a new active principle; b) the active principle is already available in a conventional pharmaceutical form; and c) the active principle is available as a modified release dosage form with which the new form is not bioequivalent. In case a) drug development clearly proceeds as with any other new clinical entity, but in addition "the therapeutic objectives and rationale for developing" a prolonged release product must be provided. Unless the reasons appear evident, some forms of comparison with a conventional release form or a solution will probably be needed for marketing authorization to be granted. In case b), recommendations contained in the "Note for Guidance" on clinical testing will have to be followed. For case c) no clear recommendations are available and it would probably be more efficacious to develop a new and bioequivalent modified release dosage form rather than to embark into a full clinical program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357577 TI - Microbiosensors for acetylcholine and glucose. AB - Microbiosensors based on carbon and and platinum fibers are described. Carbon fibers were used to construct microelectrodes of 7 microm diameter. Electrochemical operations for pre-electrolysis and measuring were examined for the highly sensitive determination of hydrogen peroxide. A triangular potential ( 2 to +2V vs Ag/AgCl) was applied before measuring each pair of double pulses (first pulse: 750 mV; second pulse: 1100 mV). The determination limit was 0.1 microM of hydrogen peroxide. The reproducible determination of hydrogen peroxide is possible even in samples containing albumin protein. The separation of hydrogen peroxide from ascorbic acid is also possible because the oxidation potential of ascorbic acid is different from that of hydrogen peroxide. An acetylcholine microsensor was fabricated by immobilizing acetylcholine esterase and choline oxidase on the carbon fiber by entrapment with poly(vinyl alcohol) quarternized stilbazole (PVA-SbQ). This sensor gave a linear calibration plot for the range 0.1-1.0 mM with a linear correlation coefficient of 0.9842. Glucose oxidase (GOD) and glucose dehydrogenase (GDH) immobilized cylindrical platinum microelectrodes were fabricated, and their characteristics were evaluated, respectively, by using 1,4-benzoquinone (BQ) and ferricyanide as electron mediators. Each enzyme was immobilized by using PVA-SbQ on a cylindrical microelectrode of 2 microm diameter. A linear range in the calibration curve of the GOD-based glucose microsensor was observed to be wider than that obtained using a disk electrode of 1 mm diameter. The mediated response of the 2 microm glucose sensor was compared with the response resulting from hydrogen peroxide detection. This result showed that a higher response and a wider linear range were observed with highly concentrated mediator. A much higher response of the GDH immobilized 2 microm microelectrode was obtained when not only ferricyanide but also diaphorase was employed to reoxidize the NADH produced by the enzyme reaction of GDH. The GHD-based glucose microsensor was found to be unaffected by the concentration of dissolved oxygen. PMID- 8357579 TI - Extraction, purification and evaluation of structures and physico-chemical properties of glycosaminoglycans. AB - Heparin was extracted and purified from beef intestinal mucosa. The two components, fast moving heparin and slow moving heparin were purified by selective precipitation as barium salts. Heparan sulfate was extracted and purified from beef spleen. Dermatan sulfate was purified from beef intestinal mucosa and chondroitin sulfate from bovine trachea. The purity of the purified glycosaminoglycans was evaluated by agarose-gel and cellulose polyacetate electrophoresis and by specific optical rotation. The relative molecular masses of glycosaminoglycans were estimated by high performance-size exclusion chromatography and the sulfate to carboxyl ratio by titrimetric analysis. The disaccharide pattern of heparin, fast moving and slow moving heparins and heparan sulfate were determined by specific enzymatic cleavage using heparinase I, II and III; the disaccharide composition of dermatan sulfate and chondroitin sulfate was evaluated by cleavage by chondroitinase ABC. The disaccharides obtained by enzymatic cleavage were qualitatively and quantitatively analysed by strong anion exchange-high performance liquid chromatography. The sulfate to carboxyl ratios of glycosaminoglycans were also determined by this technique and compared with the values obtained by titrimetric analysis. PMID- 8357580 TI - Transconjunctival approach vs subciliary skin-muscle flap approach for orbital fracture repair. AB - OBJECTIVE: To compare the transcutaneous and transconjunctival approaches for repair of orbital rim and floor fractures. DESIGN: We conducted a retrospective study of the occurrence of eyelid retraction following the repair of 63 orbital fracture, 27 with the subciliary skin-muscle flap approach and 36 with the transconjunctival preseptal approach. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Fifty-nine patients underwent 63 orbital explorations. INTERVENTIONS: Of the 27 transcutaneous explorations, 24 were done early within the first 2 weeks of injury and three were performed for correction of late posttraumatic enophthalmos. Of the 36 transconjunctival explorations, 25 were done early and 11 were performed for correction of late posttraumatic enophthalmos. OUTCOME MEASURE: Clinically noted complications. RESULTS: We found a 12% rate of transient ectropion and a 28% rate of permanent scleral show with the subciliary skin-muscle flap approach compared with no transient ectropion and a 3% rate of permanent scleral show with the transconjunctival approach. CONCLUSIONS: We believe that the transconjunctival approach provides excellent exposure with less risk of postoperative eyelid retraction and ectropion. PMID- 8357581 TI - Expanded polytetrafluoroethylene (Gore-Tex soft-tissue patch) in facial augmentation. AB - BACKGROUND: Expanded polytetrafluoroethylene (EPTFE) (Gore-Tex soft-tissue patch) has received favorable clinical reports for use in facial augmentation procedures. We evaluated the EPTFE soft-tissue patch in short-term (3-week), intermediate-term (6-month), and long-term (12-month) animal models. METHODS: Nine pathogen-free male and female New Zealand white rabbits weighing 2 to 4 kg were used. After implantation of the EPTFE soft-tissue patch, the animals were carefully observed on a daily basis for signs of wound infection, seroma, or hematoma formation. The stability of the implant was evaluated and graded after the animals were killed. Tissue specimens, including skin, implant, and underlying bone, were removed en bloc. These blocks were sectioned and stained for histologic evaluation. A portion of these blocks were used for scanning electron microscopy. RESULTS: The material increased in stability over time and showed minimal inflammatory cell response and only a delicate fibrous capsule, even in long-term implants. Ultrastructural analysis demonstrated close apposition of the material to tissue, suggesting good interface bioactivity. CONCLUSIONS: The EPTFE soft-tissue patch appears to be safe and reliable material for augmentation, demonstrating high biocompatibility, low tissue reactivity, and increasing stability over time. PMID- 8357582 TI - Verapamil enhances the survival of primary ischemic venous obstructed rodent skin flaps. AB - The effect of verapamil, a calcium channel blocker, on the survival of skin flaps subjected to primary venous obstruction was studied. Skin flaps 9 x 4 cm, which are axial patterns with random extension, were elevated in Sprague-Dawley rats. A microvascular clamp was placed on the vein alone for 8 hours. Group 1 received verapamil (0.3 mg/kg) before flap elevation and before clamp release; group 2 received saline on the same schedule. Group 3 received verapamil (0.3 mg/kg) as above, plus every 8 hours for 5 days postoperatively. Group 4 received saline on the same schedule. There was no difference in survival between groups 1 and 2. Group 3 had 100% improvement in the flap survival compared with group 4 (78% vs 37%). Verapamil, if administered for the duration of the experiment, significantly increased flap survival. PMID- 8357583 TI - Botulinum toxin for the treatment of hyperfunctional lines of the face. AB - OBJECTIVE: To determine the effectiveness of botulinum toxin injections for the management of hyperfunctional facial lines in patients with dystonia. DESIGN: Twenty-six patients were included in the study: 24 patients had dystonic movement of the face as either a primary or secondary component, and two patients were treated for purely hyperfunctional lines. Botulinum toxin type A was injected via a monopolar hollow-bore Teflon-coated electromyography needle into the facial muscles associated with the hyperfunctional lines. Doses were divided into 1.25- to 10-U aliquots. Qualitative assessments by the patient and physician were made before injection and 2 to 3 weeks after injection. PATIENTS: Twenty-six patients (two male and 24 female) with hyperfunctional lines were included. The ages were from 32 to 84 years with an average age of 59 years. Twenty had dystonia, four had hemifacial spasm, and two had pure hyperfunction without neuromuscular disease. RESULTS: All of the patients had an effect of toxin within the first 24 to 72 hours. All of the patients experienced benefit from the toxin injections with partial or total resolution of painful contractions or unsightly hyperfunctional lines and spasms. The effects of the injection lasted 3 to 6 months. No systemic side effects were noted. Adverse effects included mild, temporary eyelid or lip weakness. CONCLUSION: Based on this initial pilot study, botulinum toxin may be an important new option for the treatment of patients with hyperfunctional facial lines. PMID- 8357585 TI - Long-term stability of two different mandibular bridging systems. AB - To evaluate the benefits of narrow-beam roentgenography and spiral tomography for examination and monitoring of screw and plate fixation to bone we studied 22 rigid plate bridgings of mandibular defects. The plate reconstructions were of long duration or considered permanent. In 13 patients, AO-THORP (AO: Arbeitsgemeinschaft fur Osteosynthesefragen; THORP: Titanplasma-beschichteten Hohl- und Vollkern-Rekonstruktionsplatten-Systems) reconstructions were used and in nine classic AO stainless steel plate bridgings. With the AO-THORP system, good bone apposition to the screws was evident in 96% (73/76 screws) of the cases. Fixation using the classic AO screws, however, was inadequate in 30% (20/66 screws) of the cases. Plate loosening was noted in 56% (5/9 plates). Examination using narrow-beam roentgenography and spiral tomography provided detailed information about bone resorption around the screws and provided a reliable tool for deciding on a follow-up regimen. When complications occur, they can be detected and treated early, reducing patient morbidity. In our opinion, classic AO plate bridging should always be considered temporary. PMID- 8357586 TI - Cause for intractable chronic cough: Arnold's nerve. PMID- 8357587 TI - Allergic Aspergillus sinusitis. PMID- 8357584 TI - Surgical treatment of obstructive sleep apnea. Technical variations. AB - OBJECTIVE: To determine the effectiveness of the two basic surgical types of uvulopalatopharyngoplasty (UPPP), as classified by us. The two basic surgical variations of UPPP differ for the width of the anteroposterior palatal resection, being 1 to 2 cm (type 1) and 0.5 to 1.0 cm (type 2). DESIGN: Randomized, retrospective study. PATIENTS: Eighty-seven patients with obstructive sleep apnea hospitalized in our department from 1983 to 1991. All patients had a complete preoperative and postoperative polysomnographic evaluation. RESULTS: The operation was found to be an effective treatment of obstructive sleep apnea in most patients. Snoring improvement was found in 95% (29/31) of patients with type 1 UPPP and in 96% (54/56) of the patients with type 2 UPPP, whereas, apnea index improvement was detected in 65% (20/31) of the patients with type 1 UPPP vs 64% (36/56) of the patients with type 2 UPPP. Postoperative dysphagia was found in 94% (29/31) vs 79% (44/56), P = .0025; nasal reflux was found in 81% (25/31) vs 11% (6/56), P = .0001; and hypernasality was found in 100% (31/31) vs 13% (7/56), P = .0001, in type 1 and type 2 UPPP operations, respectively. Chi-square analysis shows highly significant differences. CONCLUSIONS: Type 2 UPPP is the recommended surgical procedure of obstructive sleep apnea, mainly due to the minimal postoperative morbidity. PMID- 8357588 TI - Cleft lip and palate surgery in La Ceiba, Honduras. PMID- 8357589 TI - Chlamydia species and Mycoplasma species in recurrent tonsillitis. PMID- 8357591 TI - Pathologic quiz case 1. Clear cell carcinoma of the nasal cavity. PMID- 8357590 TI - Pathologic quiz case 2. Benign mesenchymoma. PMID- 8357592 TI - Case report. PMID- 8357593 TI - Smokeless tobacco usage associated with oral carcinoma. Incidence, treatment, outcome. AB - Smokeless tobacco usage, particularly by young men and boys, has increased dramatically in the United States. To assess their possible risk, we reviewed the records of 128 patients with oral carcinoma who had used smokeless tobacco exclusive of other carcinogens. Most were elderly white women (average age, 78 years), 78% of whom had used smokeless tobacco for 40 or more years. The median duration of symptoms before presentation was only 3 months, yet initially 42% of these patients had T3 or T4 lesions and 30% had nodal metastases. Forty-two percent had posttreatment recurrence at the presenting site (average, 8.2 months); 26% had a second oral-cavity tumor at a new site more than 24 months after treatment (average, 49.3 months), indicative of a field cancerization phenomenon. Forty-seven percent were alive after 3 years and 37% after 5 years. These findings emphasize that strong preventive programs are needed if today's young users of smokeless tobacco are not to form future oral cancer patient populations. PMID- 8357594 TI - Total glossectomy with laryngeal preservation. AB - OBJECTIVE: To evaluate the results of a planned combined therapy with surgery and postoperative radiotherapy in the management of large (T3 to T4) squamous cell carcinomas of the tongue-tongue base in properly selected patients. PATIENTS AND METHODS: Twenty-one patients underwent this procedure in a 4-year period. The selection criteria were directed to identify those patients in whom laryngeal preservation was feasible and who were motivated. Five categories of patients were included: those with (1) large primary tumors of the tongue-tongue base; (2) recurrence after initial radiotherapy, brachytherapy, chemotherapy, or a combination of these modalities; (3) recurrence after initial surgery and radiotherapy; (4) double primary tumors; and (5) second or third primary tumors arising in the tongue or base of the tongue. Preoperative investigation included examination under anesthetic and magnetic resonance imaging. Depending on the proximity of the primary tumor to the mandible, a mandibular split, a marginal resection, or a segmental resection was carried out. Soft-tissue replacement was achieved by a myocutaneous or a muscle flap of the pectoralis muscle with split skin. Whenever possible tissues of the contralateral floor of the mouth were also used. Laryngeal suspension was performed in all cases. Postoperative radiotherapy consisted of megavolt therapy, 66 Gy in 6 weeks to the primary site and both sides of the neck. RESULTS: Resumption of swallowing and speech was achieved in all patients. External deformity was slight. Patients were able to return to their families. CONCLUSIONS: Total glossectomy with laryngeal preservation in properly selected patients provides local and regional control and preserves quality of life. PMID- 8357595 TI - Clinical underestimation of laryngeal cancer. Predictive indicators. AB - OBJECTIVE: To evaluate the accuracy of clinical staging of advanced laryngeal cancer and to morphologically analyze the underestimated cases. DESIGN: We conducted a retrospective histopathologic study of larynges from patients who had had total laryngectomy and were seen over a 21-year period. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Forty-one patients had clinically staged T3 laryngeal cancer and 16 patients had T4 cancer. INTERVENTION: Patients all underwent wide-field total laryngectomy. All larynges were processed as whole organ serial sections in the coronal plane. OUTCOME MEASURE: The incidence of clinically underestimated laryngeal cancer. During this investigation, it became obvious that predictive indicators of thyroid cartilage involvement could be established. RESULTS: Clinical underestimation had been made in approximately 50% of all T3 laryngeal cancer cases. The extent of the cartilage involvement in the underestimated group was characterized by microinvasion without penetration; approximately 90% of the cartilage involvement affected the thyroid notch and adjacent area. We established five objective indicators of thyroid cartilage involvement: (1) extensive cartilage ossification (risk for cartilage involvement, 73%); (2) glottic fixation (54%); (3) transglottic cancer (74%); (4) tumor length longer than the entire vocal fold length or longer than 2 cm (66%); and (5) extensive involvement of the anterior commissure (67%). CONCLUSIONS: Clinical underestimation of T4 laryngeal cancer was high because thyroid cartilage involvement was not accurately diagnosed. We believe our indicators of thyroid cartilage involvement will provide objective guidelines for laryngeal cancer staging and will contribute to more reliable clinical cancer-staging decisions. PMID- 8357596 TI - Supraomohyoid neck dissection in the treatment of head and neck tumors. Survival results in 212 cases. AB - Elective supraomohyoid neck dissection is considered part of standard treatment of oral and oropharyngeal cancer in most institutions, but its role in the treatment of clinically positive neck cancer remains a subject of controversy. The main object of this study is to report the results of 212 consecutive patients who underwent supraomohyoid neck dissections from 1954 to 1990. Most patients had squamous cell carcinoma of the oral cavity. Eighty-six patients (40.6%) had histologically positive lymph nodes in the surgical specimen (sensitivity, 0.55; specificity, 0.53). At the study closing date there were 58.8% actuarial 10-year overall survival rates. Forty-five patients (21.2%) had 50 tumor recurrences (32 local, 13 regional, five distant), and in 40 patients (18.8%) a second primary tumor was diagnosed. A multivariate regression technique based on Cox's proportional hazards model was used, and age (65 years or younger vs older than 65 years) represented the variable with the highest predictive strength with respect to overall survival (relative risk, 2.3). Tumor site, sex, and histologically proved metastasis were also associated with overall survival rates. The same variables were also related to the risk of recurrence. In conclusion, the death rate is mainly related to the control of the primary site tumor and the occurrence of a second primary tumor rather than to neck recurrences. It confirms that supraomohyoid neck dissection is an adequate elective procedure and possibly sufficient in the treatment of a selected group of patients with lip cancer with positive nodes at level 1. PMID- 8357597 TI - Squamous cell carcinoma of the maxillary sinus. AB - Eighty-five patients with squamous cell cancer of the maxillary sinus received all of their treatment at The University of Texas M.D. Anderson Cancer Center between the years 1971 and 1986. Their records were evaluated according to stage, disease at presentation, symptoms and signs at presentation, treatment, and outcome. There were no differences in locoregional control or survival between groups treated with surgery alone vs surgery plus radiotherapy. Careful analysis of the data indicates that there was almost certainly some selection bias for the patients undergoing combination therapy, as most of this group had historically adverse prognostic factors identified. Those patients who underwent radiotherapy alone or chemotherapy presented with either metastatic or locally advanced disease and were treated with palliative intent; therefore, comparison between this group and standard therapy groups was impossible in this retrospective review. Although it is tempting to speculate that combination therapy improved locoregional control and survival in patients with more advanced disease, none of the data presented in this review reach statistical significance. Furthermore, there is no difference in survival in this population compared with a study at this institution 20 years ago. Squamous cell cancer of the maxillary sinus continues to be a challenging neoplasm. Radiotherapy may improve locoregional control and survival in a group of patients with more advanced disease and may have its greatest utility in earlier-stage disease. A multi-institutional prospective trial is needed to find ways to improve outcome in this patient population. PMID- 8357598 TI - Angiosarcoma of the head and neck. The UCLA experience 1955 through 1990. AB - Between 1955 and 1990, 28 patients with angiosarcoma of the head and neck were seen at UCLA Medical Center, Los Angeles, Calif. Half the lesions arose on the scalp; the remainder occurred in the soft tissues of the face and neck. Nine patients presented with multifocal disease. Follow-up ranged from 3 to 159 months, with a median of 32 months. The overall prognosis was poor, with a 5-year disease-free survival of 26% (7/27 patients). Of 21 patients having recurrences after primary treatment, 90% (19/21 patients) had a component of local failure. Distant metastasis had developed in nine patients at last follow-up. Of patients treated initially with surgery alone, 8% (1/12 patients) remain disease free vs 67% (4/6 patients) who received postoperative radiation therapy, with or without chemotherapy. Only one (14%) of seven patients treated primarily with radiation therapy with or without chemotherapy was rendered disease free. Angiosarcoma usually presents with high-grade histologic features and frequently with multifocal disease. There is propensity for both local recurrence and distant metastasis. Our results and a review of the literature suggest that combined modality therapy offers the best chance for long-term control in patients with angiosarcoma of the head and neck. PMID- 8357599 TI - External septorhinoplasty in children: Outcome and effect on growth of septal excision and reimplantation. AB - Outcome and effect on nasal growth of external septorhinoplasty was evaluated in 32 children. All had septal disease anterior to the nasal spine. In all cases, the cartilaginous septum was totally excised, refashioned, and then reinserted. Sixteen children with follow-up for more than 2 years were identified. Nine children had preoperative and postoperative nasal airflow studies and demonstrated a reduction in total nasal airway resistance, from a mean untreated value of 6.1 cm of water per centimeter per second preoperatively to a mean of 2.5 cm of water per centimeter per second postoperatively. IN 10 of these 16 children, six postoperative anthropometric measures and one index were determined, and these measurements were within the range of age- and sex-specific normative data from the Craniofacial Measurements Laboratory at the Hospital for Sick Children, Toronto, Ontario. PMID- 8357600 TI - Transconjunctival blepharoplasty. Complications and their avoidance: a retrospective analysis and review of the literature. AB - The transconjunctival approach to lower eyelid blepharoplasty is becoming increasingly popular. From 200 transconjunctival blepharoplasties performed between 1984 and 1991, 40 randomly selected cases were reviewed to identify the complications associated with this technique. This represents the largest reported series (to our knowledge) in the English-language otolaryngology head and neck surgery literature. A review of the literature was performed to compare this series with reported complications associated with this approach, as well as to compare the reported complications from the transcutaneous method. Discussion on how to best avoid these complications is included. We found that the transconjunctival approach avoided the most common complication associated with transcutaneous blepharoplasty, lower lid malposition. Inadequate fat removal, the most common complication when the transconjunctival method was used, was believed to be best avoided by the careful graded and through removal of herniated lower lid fat. Patients exhibiting prominent fat without excess lower lid skin were found to be ideal candidates for transconjunctival blepharoplasty. PMID- 8357602 TI - Lysozyme and lactoferrin in human maxillary sinus mucosa during chronic sinusitis. An immunohistochemical study. AB - Immunohistochemistry was used to study the localization of lysozyme (LZ) and lactoferrin (LF) in the human sinus mucosa during recurrent and chronic sinusitis. Serous cells of submucosal mixed glands and polymorphonuclear leukocytes both displayed a strongly positive staining reaction to both LZ and LF in the normal mucosa. A positive though weak staining for LZ and LF could also be found occasionally within goblet cells. In the mucosa from patients with recurrent or chronic sinusitis, the staining reaction to LZ appeared to intensify in goblet cells. Furthermore, an increased immunoreactivity of glands vis-a-vis LZ and LF was also noted occasionally. Atypical glands were frequently found in mucosa from patients with chronic sinusitis. The epithelium of these latter glands often showed an intense staining reaction to LF, but a rather weak reaction to LZ. The results of the present study suggest that the observed increase in LZ and LF secreting activity of goblet cells, epithelial cells and newly formed atypical glands may play a part in the defense mechanism of the sinus mucosa during the course of chronic sinusitis. PMID- 8357603 TI - Keratosis of the tympanic membrane and deep external auditory canal. A defect of auditory epithelial migration. AB - We have previously described the pathways of movement of epithelium on the tympanic membrane, showing that there are two discrete and separate zones. Four cases of keratosis of the tympanic membrane and deep external auditory canal are here reported. All patients complained of tinnitus and other aural symptoms. Sequences of otoscopic photography of daubs of dye placed on the tympanic membrane showed an abnormal anterior movement over the whole tympanic membrane in two cases and complete paralysis of movement in the two others. These findings suggest that the disorder arises from damage to basal epidermal cells caused by inflammation, which is probably due to infection. Treatment is by suction stripping of keratin from the eardrum. Careful examination of the eardrum under magnification is required in all cases of tinnitus so as to detect this condition. PMID- 8357601 TI - The nature of the head and neck cancer. AB - Squamous cell carcinoma of the head and neck is a disease predominantly of males and is due to a variety of known environmental irritants, notably cigarette smoke. Dietary, viral and immunological factors may also be relevant. Head and neck squamous cancers express epidermal growth factor receptors and some show weak levels of oestrogen receptor activity, but a reliable serum marker of tumour burden remains to be identified. The prognosis is found to be less favourable in females, in those with advanced T stage, in association with multiple node involvement, especially where extracapsular spread is present and where the T4/T8 ratio is elevated. Administration of heterologous blood during therapy may also have an adverse effect on prognosis. Interested clinicians must remember that most cases are preventable. PMID- 8357604 TI - Benign keratoma of the vocal cords. AB - Benign keratomas are true benign tumors of the vocal cords that are to be differentiated clinically and histologically from malignant, inflammatory and reactive lesions which may also result in superficial keratinization. Clinically, keratomas present as flat, warty or papillary lesions with varying keratinization surrounded by a normal-appearing ("healthy") epithelium. They are usually unilateral, with their extents varying from 2 to 3 mm in diameter to tumors occupying the entire vocal cord. Histology shows grade I or grade II epithelial hyperplasia without any signs of inflammation. In the present study 61 patients with benign keratomas were treated by excisional biopsies alone. Fifty-seven patients were followed for a minimum of 7 months and a maximum of 16.5 years. Two patients developed recurrent keratomas. To date none of the patients has developed an invasive vocal cord carcinoma or a carcinoma in situ. PMID- 8357605 TI - Nucleolar organizer regions in carcinomas of the oropharynx and hypopharynx. AB - It is supposed that the nucleolar organizer regions (NORs), genes on which ribosomal RNA is coded, may contain information on the structure of the nucleolus and on nucleolar activity which permits discrimination between normal and neoplastic cells and their proliferation activity. In the present study, the histological sections of 144 patients with carcinomas of the oropharynx and hypopharynx were studied in a retrospective approach to determine the absolute NOR counts per 100 nuclei and investigate their influence on the prognosis and extent of lymphogenic formation of metastases. An absolute NOR count of 681 per 100 nuclei was found to give reliable discrimination between stage N0 or N1 carcinomas and stage N2 or N3 disease. PMID- 8357606 TI - A peptide-like putative marker substance of laryngeal cancer patients. AB - Acidic ethanol precipitation, gel-filtration chromatography (Sephadex G-25) and capillary isotachophoresis were performed on serum and tumor tissue samples from eight patients with stage III and IV laryngeal cancers. An anionic 0.3-5 kDA molecular mass substance that was probably peptide was recorded in both the serum and cancer tissue, but could not be shown in the serum of five control subjects. This substance disappeared from the sera of four patients after total laryngectomy and they have now lived without tumor recurrence for about 2 years. Three of the other four patients developed tumor recurrences while one patient has remained tumor-free. Our findings support a hypothesis that the peptide-like molecule is characteristic of laryngeal cancer and can possibly be used for monitoring the disease. PMID- 8357607 TI - A quantitative study of nerve fibers in the human facial nerve. AB - The facial and intermediate nerves were quantitatively evaluated in seven patients who died from systemic malignancies not involving the facial nerve. In addition, five of the specimens were also qualitatively evaluated by measuring the total and axon diameters of the facial and intermediate nerve fibers. In two cases the facial nerve fibers were counted at five different levels. The total number of myelinated nerve fibers in the facial nerve varied from 7500 to 9370. The total number of myelinated nerve fibers in the intermediate nerve varied between 3120 and 5360. The peak diameter of the facial nerve axon was between 4 and 6 microns, and was between 2 and 3 microns in the intermediate nerve. When comparing nerve segments at different anatomical levels, the largest amount of nerve fibers was found at the level of the middle mastoid portion. However, this number did not reach the amount of nerve fibers counted in the internal acoustic meatus. PMID- 8357608 TI - Chondrosarcoma of the larynx. AB - Chondrosarcoma of the larynx is a rare, slow-growing malignant tumor. One hundred and fifty cases of this entity have been reported in the literature. In 75% of cases the site of involvement was the cricoid cartilage, while 20% have involved the thyroid cartilage. The tumor presents as a space-occupying lesion in the subglottic region, or as a neck mass. An insidious, slowly progressing disease course associated with hoarseness and dyspnea accounts for usual delays in arriving at a diagnosis. We report our experiences with six cases of this entity and discuss a diagnostic and therapeutic approach. Whenever possible a conservative surgical management should be attempted. PMID- 8357609 TI - Inner ear damage due to lipoid nephrosis. AB - Inner ear pathology was studied in adult rats with lipoid nephrosis induced by puromycin aminonucleoside. Although no abnormality was observed in auditory brain stem responses, significant changes were noted in the stria vascularis. The most striking observation was that intermediate cells were markedly swelled, there-by pressing adjacent marginal cells. Severely affected marginal cells have vacuoles and increased lysosomes and protruded toward the endolymphatic space. The organ of Corti remained virtually intact. Although the vestibular maculae were relatively normal, type I hair cells in the semicircular canal underwent a conspicuous vaculolization. These findings support a postulate that the inner ear is liable to damage in lipoid nephrosis. PMID- 8357610 TI - Biochemical characterization of mucous glycoproteins secreted by in vitro chinchilla middle ear epithelial cells. AB - A method for middle ear epithelial (CMEE) cell culture with active mucus secretory function has been successfully developed, using the chinchilla as an animal model. CMEE cells were dissociated by protease digestion from the middle ear mucosa. The CMEE cells grown in primary culture incorporated [3H]glucosamine into a glycoconjugate after its release into medium. This substance was characterized biochemically as mucin, although the production of mucin by the cells required growth on a substratum of collagen gel. These cultures provide an excellent model for studying factors that regulate synthesis and secretion of glycoproteins in CMEE cells. PMID- 8357611 TI - An immunohistochemical and electrophysiological study on Isk protein in the stria vascularis of the guinea pig. AB - The reaction product against rat Isk protein antibody was demonstrated on the endolymphatic surface of the marginal cell of the guinea pig, using an immunohistochemical method. Clofilium, a potassium channel blocker which has been previously found to block rat kidney Isk channels, decreased the endocochlear potential (EP) when applied by perilymphatic perfusion and iontophoresis into endolymph. This finding of a decreased EP supports the presence of Isk protein on the endolymphatic surface of the marginal cell. PMID- 8357612 TI - A three-dimensional reconstructive study of the layer structure of the human vocal cord. AB - The purpose of this investigation was to clarify the detailed histological structure of the human larynx and to clarify the cause of adaptation in high frequency vibrations using three-dimensional histological reconstructions of human true vocal cords. In a first series of studies, 54 intact adult larynges were obtained from 398 human cavaders with known histories. Four of these laryngeal specimens were fixed in 10% formalin. Three of these were decalcified and embedded in paraffin and the other in Technovit-7100. The layer structure of each larynx was investigated with a three-dimensional reconstruction method using a personal computer. Results demonstrated that the elastic fiber layer in the superior surface of the vocal cord was wider than that in the inferior surface. The collagen fiber layer extends from the anterior commissure in a posterior direction. The elastic fiber layer connected both the anterior and the posterior macula flava, while the collagen fiber layer connected the thyroid cartilage and the anterior macula flava. PMID- 8357613 TI - Innovations in auxiliary dental education. PMID- 8357614 TI - A WDA interview with MUSOD's Dean...Dr. Kenneth L. Zakariasen, Jr.. Interview by Dr. Peter H. Jacobsohn. PMID- 8357615 TI - Microbial purification technique of mineral dressing plants reject waters. AB - Earlier investigations on laboratory and pilot plant scale have shown the resort to microorganisms to be a practicable approach to the problem of purifying mineral dressing plant reject waters from residual flotation reagents and/or metal ions. In spite of the proven effectiveness of this method, one major drawback, namely the pathogenicity of some microorganisms, has so far hampered its application on a commercial scale. A research programme, aimed at developing a microbial reject water purification technique utilizing non-pathogenic strains was thus drawn up and is currently being implemented. Strains such as Bacillus subtilis, Saccharomyces cerevisiae, Bifidobacterium bifidum, Lactobacillus acidophilus and Acinetobacter calcoaceticus, which are not harmful to human health, some of them being commonly found in the human intestine, have been successfully tested for removing alkylsulphates, alkylamines and fatty acids from solutions simulating flotation plant tailings waters. Removals as high as 90% in less than 48 h can be easily achieved with no nutrient requirements, since in most cases the flotation reagent residue to be removed is metabolized by the microorganisms themselves. PMID- 8357616 TI - Amplification of ribulose biphosphate carboxylase/oxygenase large subunit (RuBisCO LSU) gene fragments from Thiobacillus ferrooxidans and a moderate thermophile using polymerase chain reaction. AB - Southern blot analysis of DNA from an iron-oxidising moderate thermophile NMW-6 and from Thiobacillus ferrooxidans strain TFI-35 demonstrated sequences homologous to the RuBisCO LSU gene of Synechococcus. DNA fragments (457 bp) encoding part of the RuBisCO LSU gene (amino acids 73-200) were amplified from the genomic DNA of Thiobacillus ferrooxidans and the moderate thermophile NMW-6 using the polymerase chain reaction (PCR) technique (Saiki et al. (1985) Science 233, 1350-1354). A comparison with the LSU sequences from T. ferrooxidans, Alcaligenes eutrophus, Chromatium vinosum, Synechococcus and Spinacea oleracea, which all have RuBisCOs with a hexadecameric structure, showed that the RuBisCO LSU gene sequence from NMW-6 appeared to be most closely related to that of the hydrogen bacterium A. eutrophus which showed 71.9% homology at the amino acid level. Despite its physiological similarity, T. ferrooxidans showed only 64.1% homology to the amino acid sequence from NMW-6 and had the lowest DNA homology (60.9%) of the hexadecameric type RuBisCOs. In the region sequenced, T. ferrooxidans and the RuBisCOs of the phototrophs C. vinosum, Synechococcus and S. oleracea, had 17 residues that were completely conserved which were substituted in both NMW-6 and A. eutrophus, 11 of these being identical substitutions. Comparison of the nucleotide and derived amino acid sequences of the RuBisCO LSU fragment from T. ferrooxidans with other RuBisCO sequences indicated a closer relationship to the hexadecameric type LSU genes of photosynthetic origin than to that of A. eutrophus. The T. ferrooxidans amino acid sequence showed 93.8%, 78.9% and 77.3% homology, respectively, to the C. vinosum, Synechococcus and S. oleracea (spinach) sequences but only 56.2% to A. eutrophus. The DNA sequence from Rhodospirillum rubrum, which has the atypical large subunit dimer RuBisCO structure with no small subunit, showed 39.2% and 42.7% homology, respectively, with the sequences of NMW-6 and T. ferrooxidans, and 25.0% and 29.7% amino acid homology, indicating that the DNA homology was substantially random in nature. PCR fragments (126 bp) that overlaped the last 15 codons of the fragments above were also amplified and sequenced. They showed incomplete homology with the larger fragments, supporting evidence obtained from Southern hybridizations that T. ferrooxidans and the moderate thermophile NMW-6 have multiple copies of RuBisCO LSU genes. PMID- 8357617 TI - Enzymes of aerobic respiration on iron. AB - Bacteria capable of aerobic respiration on ferrous ions are spread throughout eubacterial and archaebacterial phyla. Comparative spectroscopic analyses revealed that phylogenetically distinct organisms expressed copious quantities of spectrally distinct redox-active biomolecules during autotrophic growth on soluble iron. Thiobacillus ferroxidans, Leptospirillum ferrooxidans, Sulfobacillus thermosulfidooxidans, and Metallosphaera sedula possessed iron respiratory chains dominated by a blue copper protein, a novel red cytochrome, a novel yellow protein, and a novel yellow cytochrome, respectively. Further investigation of each type of respiratory chain will be necessary to deduce the advantages and disadvantages of each. PMID- 8357618 TI - Imaging the sphenoid bone and basiocciput: anatomic considerations. AB - The sphenoid bone is a complex structure with an intricate embryologic origin. It is centrally located within the skull base and articulates with almost every structure in the skull and face. The sphenoid bone contains multiple foramina and fissures accommodating numerous vessels and nerves. This report reviews the embryology of the sphenoid bone and its normal postnatal changes, and describes the normal anatomy of the sphenoid bone and its numerous foramina and fissures. Computed tomography (CT) and magnetic resonance (MR) are used to illustrate developmental changes and normal anatomy. PMID- 8357619 TI - Imaging the sphenoid bone and basiocciput: pathological considerations. AB - Many diverse pathologic processes can involve the sphenoid bone because of its complex embryologic origin. In addition to primary neoplasia, the central location of the sphenoid predisposes it to involvement by many intracranial and extracranial lesions. The presence of multiple foramina and fissures offer "paths of least resistance" that allow the spread of pathology across the skull base. Sphenoid sinus disease also accounts for a number of pathologic entities occurring in this vicinity. This article reviews the more common lesions affecting the sphenoid bone as well as their CT and MR appearance. PMID- 8357620 TI - The sellar/parasellar endocrinopathies: a brief clinical overview. AB - Endocrine disorders of the pituitary and other hypothalamic structures are reviewed. Anterior and posterior pituitary physiology is described as well as hormone-producing tumors that cause Cushing's disease, hyperprolactinemia, acromegaly-gigantism, and precocious and delayed puberty. The diagnosis and management of diabetes insipidus caused by hypothalamic-posterior pituitary disorders complete the overview. PMID- 8357621 TI - Imaging of the sella: anatomy and pathology. AB - The hypophysis cerebri, or pituitary gland, is a complex neuroendocrine organ involved in the control of a variety of homeostatic mechanisms. Subtleties in the internal anatomy of this gland are now becoming appreciated, such as the topographic arrangements of pituitary cell types and specializations in its regional microcirculation. A large number of potential lesions may affect the pituitary, including tumors (adenomas, Rathke cleft cysts, and craniopharyngiomas), inflammatory processes (adenohypophysitis, infections), and vascular lesions (apoplexy, infarction). Diseases isolated to the posterior lobe and stalk (eg, pituitary dwarfism, choristoma, diabetes insipidus) are also well recognized. Modern radiologic techniques like computed tomography (CT) and magnetic resonance (MR) imaging have provided new insights into the morphologic changes of the gland that occur both in health and in a variety of diseases. The picture of the gland that has emerged from this research is a dynamic one: The pituitary undergoes dramatic changes in size and shape throughout life that must be recognized when assessing it for pathologic change. PMID- 8357622 TI - Normal imaging anatomy of the suprasellar cistern and floor of the third ventricle. AB - This article discusses the gross, functional, and imaging anatomy of the suprasellar cistern and its contents as well as the structures that form its borders, among the most important being the floor of the third ventricle and associated structures. Specific structures discussed include the optic chiasm and optic tracts, the anterior third ventricle, the tuber cinereum, the pituitary stalk (infundibulum), the choroidal fissure, the lamina terminalis, the gyrus rectus, the uncus, and the cerebral peduncles. PMID- 8357623 TI - Clinical manifestations of lesions of the suprasellar and parasellar regions: a neuro-ophthalmologic perspective. AB - Radiologists, neurologists, and ophthalmologists must develop common ground in describing the clinical manifestations of and terminology used in lesions of the basilar cisterns and parasellar region. This article attempts to bridge that communications gap using lesions of the orbital apex, cavernous sinus, sella turcica, and parasellar regions as examples. PMID- 8357624 TI - Suprasellar masses: diagnosis and differential diagnosis. AB - Suprasellar masses are neoplastic, vascular, congenital, or infectious/inflammatory in origin. Magnetic resonance imaging (MRI) is the study of choice for evaluating suprasellar masses, although computed tomography (CT) may provide complementary information. Suprasellar masses present with a variety of neurologic or endocrine dysfunctions depending on their site of origin and mass effect on adjacent structures. Imaging characteristics of the most common suprasellar lesions are described with particular emphasis on MR findings. PMID- 8357625 TI - Petrous apex and cavernous sinus: anatomy and pathology. AB - The cavernous sinus (CS) and petrous apex (PA) are contiguous. The cavernous space and cranial nerves III and VI are intimately associated with each. To accurately interpret computed tomography (CT) and magnetic resonance (MR) images of this region, one must understand thoroughly the anatomy of the PA and CS. This article begins with a detailed review of this anatomy, followed by a discussion of pathology. Intrinsic diseases of the CS and PA are emphasized specifically. PMID- 8357626 TI - [Clinicopathologic prognostic factors of laryngeal and pharyngeal tumors. III: Supraglottic carcinoma]. AB - The factors which influenced the prognosis of 306 supraglotic carcinomas were studied. The determinate survival at 3 and 5 years was 7.8% and 57.5% respectively. The lymph node metastases and the presence of recurrence affected significantly the survival. Also showed a worse prognosis those with an advanced local stage, and the patients with excessive alcoholic consumption. Without significative prognostic influence were the grade of tumor differentiation, involvement of surgical margins, previous tracheostomy, and the existence of a second primary tumour. PMID- 8357627 TI - [Oncoprotein p21-ras expression in epidermoid carcinoma of the laryngopharynx]. AB - Ras genes can acquire transforming properties by qualitative and quantitative mechanisms. The mutated products of ras oncogenes (p21 protein) exhibit a decreased ability to hydrolyze GTP that lead to the stabilization of ras proteins in their active state and cause a continuous flow of signal transduction which may result in malignant transformation. These biochemical aberrant properties can also be achieved by an increased expression of the normal p21 protein. In this work we have analyzed the presence of ras gene mutations and the overexpression of the oncogene product p21 in the same series of squamous cell carcinoma of pharynx and larynx. Of 13 cases studied we have detected mutations in seven cases and in nine we have observed overexpression of the p21 protein. There is no correlation between ras mutations and overexpression of the p21 protein. PMID- 8357628 TI - [Correlation of auditory brainstem evoked potentials and pure tone audiometric thresholds]. AB - This work is on relation existing between the objective threshold of auditory brainstem responses in adults and those existing in the different frequencies of audiometry pure-tone, in order to make the audiometry from the objective threshold of the ABR, from the subjective threshold to the click, and the type of hearing loss in question. Such results can be transferred to children, and starting from the ABR in children we could guess their probable audiometric profiles. On that purpose we have studied the auditory brainstem responses and the pure-tone audiometry in 168 ears suffering from hearing-loss, both conductive and sensory neurals with and without recruitment, with different degrees of hearing losses and audiometric profiles. The results have confirmed the relation existing between the threshold of evoked brainstem responses and those of high frequencies, 2,000, 4,000 and 8,000 herzs. We have also proved that the threshold ABR has a predicting value on the audiometry of patients, and that the difference between the objective threshold ABR and the subjective one represents the inclination degree of the pure tone audiometry, which considerably reduces the great variability presented by the prediction of thresholds of low tones starting from ABR. PMID- 8357629 TI - [Psychological alterations in patients with cancer of the larynx before and after laryngectomy]. AB - Our work, about the psychological disorders associated with cancer of the larynx and its therapeutics, study a group of 54 neoplasicos patients who have undergone a laryngectomy, before and after surgical treatment. We analyze in the pre operation period, the relationship between the cancer and anxiety/state, comparing the patients with a serious neoplasia and those with a more benign pathology. After the operation, we study the relationship between the loss or retention of speech and the existence of anxiety/state and depression. We evaluate anxiety through the (STAI) of Spielberger and depression through the SDS scale of Zung. The pre-operative results indicate that the patients have levels of A/E significantly greater (p < 0.0001) than the mean score in the control group, without there being any significant difference according to the gravity of the cancer. Patients that have lost the capacity to speak after the surgical treatment, have significantly higher levels of anxiety and depression than the control group and those patients that have retained the capacity to speak (p < 0.0005). Other results about the relationship between the two disorders studied and variables of personality, can be found in the analysis section and in the discussion of the results. PMID- 8357630 TI - [Partial horizonto-vertical laryngectomy: experience of 44 cases (follow up of more than five years]. AB - The horizontal-vertical partial laryngectomy combines supraglottic and hemilaryngeal excisions of one side of the larynx and is indicated, as first choice, in the supraglottic tumours with unilateral glotoaryntenoid involvement. We have followed this theory and practice since 1974, and have studied 44 patients operated on using this technique up to 1986, who have now (1992) been followed up for more than five years. Analysis of the results shows the number of patients alive and free of tumour, and the number of decannulations, to be sufficiently high for the recommendation of this technique in the treatment of such tumours. PMID- 8357631 TI - [Epidemiologic aspects of cancer of the nasopharyngeal cavum]. AB - We have made a retrospective study of 22 patients with CC. We have studied epidemiologic and clinical factors and we related them with similar studies. PMID- 8357632 TI - [Applied anatomy for the radiologic and computed tomography study of the paranasal sinuses]. AB - The current diagnosis by images has a significant importance in the medical and/or surgical treatment of the sinusal incidences due to its great sensibility to detect local pathological signs, their limits and neighboring relations. These data are of unvaluable importance at the moment of a therapeutical decision and should be based upon common interests among otorrhinolaringologists and neuroradiologists, speaking the common language given by a firm and shared knowledge of regional anatomy. This presentation is based on the comparison between drawings which show the essential anatomical data and the computed tomography findings, supplying the necessary technical data to obtain veracious images which coincide with the surgeons' angle of view in the direct as well as in the endoscopic approach. PMID- 8357633 TI - [Comparative study of the effect of different chemical procedures on the antigenicity of allogenic transplants of the human trachea]. AB - Replacement of long tracheal segments poses some unsolved problems, specially the undisponibility of an adequated substitution material. This study deals with some of the immunological aspects of the transplantation and preservation of human tracheal grafts. Since immunological rejection occurs in the first place as a consequence of incompatibility for class II antigens (HLA-DR, -DP and -DQ), their presence and distribution was studied using monoclonal antibodies and the immunoperoxidase method. Class II expressing cells were recognized in the mucosa and the mixed glandular tissue. Furthermore we investigated the influence of different preservation methods on the antigenicity of tracheal allografts. The results showed a total destruction of these antigens. We can conclude that chemically preserved human tracheal allografts are immunologically suitable for reconstructive surgery of the trachea. PMID- 8357634 TI - [Study of the vestibulospinal reflex. Clinical applications of posturography]. AB - The vestibulo-spinal reflex is of great importance in maintaining balance--hence the interest in evaluating it objectively in patients suffering from vertigo. A review is made of the objective exploratory methods currently available, i.e., static posturography, stimulation posturography, dynamic posturography and craneocorpography. The clinical applications of posturographyare discussed, fundamentally as applied to the diagnosis of central vestibular pathology, treatment planning and evolutive monitoriacion of the patient with vertigo. PMID- 8357635 TI - [Pseudosarcoma of the larynx. Presentation of two clinical cases in our service with distinct laryngeal localization]. AB - We present two pseudosarcoma of larynx with different localization. Both with pedunculate morphologic, one in vocal cord true, another case in supraglottic. PMID- 8357636 TI - [Mucoepidermoid carcinoma of the larynx]. AB - A case report of mucoepidermoid carcinoma of the larynx es presented and the literature reviewed. The inherent difficulties in histologic mucoepidermoid carcinoma is discussed. At the present time, mucoepidermoid carcinoma of the larynx should be regarded as a separate entity, its treatment based in histological grade as well as clinical behavior. PMID- 8357637 TI - [Malignant otitis externa with disfunction of the temporomandibular articulation]. AB - Here we present a case of a female patient 70 years old stricken with diabetes mellitud 40 years of evolution with manifestations of malignant external otitis accompanied by disfunction of the temporomandibular articulation. Here we will show the clinical characteristics and the diagnosis in our patient likewise its treatment. We will expound the most important aspects of the entity at this present time. PMID- 8357638 TI - [Solitary extramedullary plasmacytoma of the larynx. Presentation of a clinical case]. AB - Extramedullary plasma cell tumours are uncommon neoplasia. Their highest incidence is in the upper respiratory tract, specially in the nasal cavity, paranasal sinuses and nasopharynx. They represent the 4% of all the non epithelial tumours of this site. Their evolution is unsteady and a 30% of the cases develop into a multiple mieoloma. PMID- 8357639 TI - [Geographic distribution of mortality from cancer of the stomach and the colon in Spain]. AB - The present study analyzes the mortality of gastric and colon cancer in Spain from 1975 to 1985, and examines the figures obtained for each Spanish province as well as in several major cities. During the study period, proportional mortality for all cancers increased, except for gastric cancer which decreased both for men and women. We found that Soria the highest mean mortality rate due to gastric cancer (81.83), whereas figures were highest for men in Segovia (97.71) and for women in Soria (66.69). By contrast, Gran Canaria had the lowest mean mortality rate due to gastric cancer (6.26), whereas lowest values were obtained for men in Tenerife (8.42) and for women in Gran Canaria (4.11). On the other hand, the highest mortality rate due to colon cancer was found in Gerona (19.11), and the sex distribution was as follows: for men the rate was highest in Gerona (22.22), and for women in Burgos (19.75). Albacete had the lowest mortality rate due to colon cancer (1.09); for men the lowest was obtained in Avila (1.20), and for women in Albacete (0.90). This geographical distribution suggest that environmental as well as dietary factors may play a role in cancer mortality. PMID- 8357640 TI - [Colorectal cancer in elderly patients: postoperative mortality and survival]. AB - Twenty percent of colorectal cancers develop in elderly patients. Since the size of the geriatric population increases this percentage will get higher. The data collected from the Cantabria Colorectal Cancer Population Registry (1989-90) were divided into two groups: patients aged > or = 80 years at diagnosis and patients aged < 80. The postoperative mortality rates were 11% vs. 7%. Emergency surgery on patients over 80 years was associated with a significantly higher incidence of perioperative deaths (26%). Three-year survival rates for the two groups (20%) were not significantly different. These data suggest that elderly patients suffering from colorectal cancer can be treated by standard methods. PMID- 8357641 TI - [Effect of antibiotic prophylaxis with vancomycin on methicillin-resistant Staphylococcus aureus infection following liver transplantation]. AB - An epidemic outbreak of Methicillin-resistant Staphylococcus Aureus (MRSA) infections affecting liver transplantation patients was detected in our hospital. In this study we describe the special characteristics of the infections and the results of prophylactic treatment with Vancomycin. Between april 1990 and december 1991, 47 patients with mean age of 54.4 +/- 10 years underwent liver transplantation. The patients were included in two chronological groups: 1) Group I: 20 patients not treated prophylactically with Vancomycin; 2) Group II: 27 consecutive patients treated with Vancomycin. Systematical cultures of body fluids for bacteria and fungi were done in every patient, and were repeated after 24 hours. The cultures were repeated again in case of sepsis. Group I patients had a significantly higher frequency of MRSA infections than group II patients. Furthermore, in patients with MRSA infection, independently of the group, duration of transplantation (p < 0.01), reoperations (p < 0.001) and prophylactic treatment with Vancomycin (p < 0.001) were significative factors. In conclusion, Vancomycin appears to be an elective prophylactic antibiotic in case of high risk of MRSA sepsis after liver transplantation. PMID- 8357642 TI - [Primary lithiasis of the choledochus: etiologic factors and structural characteristics]. AB - OBJECTIVE: To study clinical and morphological characteristics of primary gall stones in the common bile duct in order to establish a differential diagnosis with migrating stones. DESIGN: To analyze a number of clinical parameters (age, parity, evolution, number of stones and diameter), qualitative parameters (sex, obesity, cholecystitis, cholangitis, liver disease or previous biliary surgery) and statistic evaluation. To show composition of stones throw stereomicroscope, electronic microscope and dispersion analysis by X-Ray. PATIENTS: We studied 56 patients who were diagnosed and operated of choledocholithiasis. RESULTS: 21 cases (37.5%) were considered as primary stones (group "a") and 35 (62.5%) were considered as migrating stones (group "b"). We have found significant statistical differences in relationship with the age of patients (p < 0.05) and diameter of stones (p < 0.01). They were both greater in primary stones, while the rest of parameters were not significant. Brown pigment stones dominate in primary stones followed by calcium palmitate and cholesterol stones. We identified bacteria or their traces (38.1%), foreign bodies (19.04%), carbonate of calcium (38.1%) and phosphate of calcium (9.5%). CONCLUSIONS: They are clinical and morphological characteristics which may differentiate between primary and migrating common duct stones. The high incidence of germs or foreign bodies found in the core layer of stones show their importance in the formation of brown pigment. PMID- 8357643 TI - [Long-term results of endoscopic sphincterotomy]. AB - A review is made of the results of long-term endoscopic sphincterotomy. We studied 81 endoscopic sphincterotomies performed between 1980 and 1985. The technique performed, its indications and immediate complications were evaluated, along with the follow-up carried out in these patients (minimum 6 years). In view of the results obtained, the patients were classified as asymptomatic or symptomatic. Thus, immediate complications (21.9%) were all minor, with the exception of one case (1.2%) of severe complication due to acute pancreatitis. One death was recorded three days after sphincterotomy, corresponding to an elderly patient with in situ gallbladder as a consequence of biliary sepsis. In turn, 91.4% of the patients followed-up at long term remained asymptomatic. The overall results show the method to be effective, with few either immediate or long-term complications. PMID- 8357644 TI - [Methods to evaluate the hepatic metabolic capacity: pharmacologic tests]. PMID- 8357645 TI - [Composite gastric lymphoma: MALT gastric lymphoma associated with Hodgkin's disease]. AB - We report a case of MALT (Mucosa Associated Lymphocytic Tissue) gastric lymphoma which occurred in a 52-year-old woman, associated with Hodgkin's disease, Lymphocyte Predominant type, in epiploic nodes. Although many cases of composite lymphomas have been reported, we were not able to find cases of gastric MALT lymphoma associated with Hodgkin's disease. This is probably the first case reported in the literature. PMID- 8357646 TI - [Metachronous adenocarcinoma of the duodenum associated with previous colorectal carcinoma]. AB - We present two patients who developed a carcinoma of the duodenum years after a colectomy was performed adenocarcinoma of the colon. Duodenal carcinoma has been reported in patients with villous tumor of the colon, familial adenomatous polyposis, Gardner's syndrome, celiac disease and Crohn's disease. A relationship between carcinoma of the Vater's ampulla and adenocarcinoma of the colon has also been reported. However, we have not found in the literature this association in patients without familial adenomatous polyposis or Gardner's syndrome. PMID- 8357647 TI - [Enteritis caused by small intestine irradiation]. AB - Two cases of small bowel postradiation enteritis after abdominoperineal resection are presented. The interval between radiation of 60 Gy to the pelvis and perineal area and the occlusive symptoms were 3 and 6 years. One patient required a massive small bowel resection, and the second an ileo-transverse colon bypass. The first case had a partial dehiscence of the anastomosis, and the second a colonic fistula 8 months after surgery that closed after total parenteral nutrition. Both patients had abdominal wall closure defects. PMID- 8357649 TI - [Massive rectal hemorrhage caused by nonspecific colonic ulcers]. AB - Nonspecific colon ulcers are a rare disease which may produce lower gastrointestinal bleeding. A history of previous nonsteroidal anti-inflammatory drugs ingestion may be recorded in most patients. The right colon is the main location, being the cecum the most frequent site. However, they may be distributed in all the large intestine, including the rectum. We present a case of lower massive gastrointestinal hemorrhage produced by nonspecific colic ulcers requiring emergency total colectomy. Although infrequent, they have to be considered in every patient with lower gastrointestinal bleeding and previous nonsteroidal anti-inflammatory drugs ingestion. PMID- 8357648 TI - [Peutz-Jeghers syndrome with malignization of hamartomatous polyp]. AB - Peutz-Jeghers syndrome is characterized by hamartomatous polyps in the gastrointestinal tract associated with mucocutaneous melanin spots; the condition is inherited in an autosomic dominant fashion. Although the hamartomatous polyps are not regarded as malignant, there is an association between the Peutz-Jeghers syndrome and the development of carcinomas of the gastrointestinal tract. Similarly, there is an increasing evidence suggesting that hamartomas can give rise to adenocarcinomas. We present a patient with Peutz-Jeghers syndrome who developed an adenocarcinoma in an hamartomatous jejunal polyp. PMID- 8357650 TI - [Primary angiosarcoma of the spleen]. AB - Primary spleen angiosarcoma is a malignant neoplasia based on vascular tissue and it is a rare tumor (65 cases published). The clinical aspects are obscure and the specific diagnosis is made by laparotomy. The prognosis is very poor in any case and survival isn't more than two years, whenever the spleen undergoes spontaneous rupture in which case the survival should be less than six months. The splenectomy before rupture could increase survival. Patients with or without metastatic disease may be treated by chemotherapy but with poor results. Radiotherapy is used for relief the pain produced for bone metastasis. PMID- 8357651 TI - [Colonoscopic diagnosis of the origin of a right inguinal abscess]. PMID- 8357652 TI - [Basal and postprandial blood gastrin in duodenal ulcer]. PMID- 8357653 TI - [Stercoral perforation of the colon]. PMID- 8357654 TI - [Iron deficiency anemia as onset form of duodenal leiomyosarcoma]. PMID- 8357655 TI - [Acute myocardial infarction following vasopressin injection for portal hypertension syndrome]. PMID- 8357656 TI - [Incidence of digestive system neoplasms. Trends. Soria 1981-1990]. AB - The aim of this study was to evaluate, to compare and to identify the various incidence rate trends in digestive tract malignant tumours in the province of Soria. Tumor sites and histological types, patient's age, sex and town and area residence were studied. All new cases of digestive tract malignant tumours were collected during the 1981-1990 period. 30.4% of all malignant tumours in men (1906 patients) and 29% in women (1,256 patients) came from digestive tract sites. Incidence rates for each site were calculated for the two 1981-1985 and 1986-1990 subperiods. The histology, rates and trends of the tumours were compared with the other national and international cancer registries. Gastric cancer showed the highest adjusted rate for men (35.1 x 10(5) and colo-rectal cancer one for women (14.7 x 10(5). The lowest rates were for men in the gallbladder (0.5) and liver (1.1) sites; and for women in the gallbladder (1.6), whose diminishing trend was significant (2.92/0.75) (p < 0.05) and liver (0.5). Colorectal cancer showed a marked increase between the two subperiods for both sexes (men: 13.1/27.6) (women: 9.8/19.2). Pancreas cancer trends ascended for both sexes (men: 1.22/2.74) (women: 0.13/1.46). Gastric cancer rates in Soria are higher than the rest of the cancer registries in Spain while gallbladder, liver, and colorectal, cancer rates are one of the lowest for both sexes. Trends are significantly increasing in colorectal sites for both sexes (p < 0.01), and for women only in the pancreas (p < 0.05). The other cancer rate sites showed lesser variations and are not statistically significant. PMID- 8357657 TI - Comparison of clinical treatment decisions with US National Institutes of Health consensus indications for lower third molar removal. AB - Treatment decisions about lower third molar surgery have important clinical and cost implications. Although indications for surgery have been the subject of a National Institutes of Health (NIH) consensus conference at which several unambiguous criteria were agreed, no prospective investigations have been carried out to compare clinic treatment decisions with these consensus criteria. Treatment decisions made by six Hospital Service oral surgeons were therefore evaluated for 72 consecutive patients (28 men, 44 women) aged 15-44 years (mean age 25 years), referred for lower third molar assessment. The presence of local disease; recurrent pericoronitis; caries not amenable to restorative measures; follicular cyst formation; internal/external resorption and periodontal disease was recorded by an independent observer immediately after treatment planning had been completed. Of the 139 third molars present, 55 were unerupted, 79 partially erupted and 5 fully erupted. Thirty patients had been scheduled for surgery under general anaesthesia (GA), 36 under local anaesthesia and six patients had not been scheduled for surgery. A total of 42 teeth, according to NIH consensus criteria, had no indications for removal, of which 27 had been scheduled for surgery. These excluded disease-free contralateral teeth that had been scheduled for removal under GA. When a single episode of pericoronitis was excluded as a valid indication, 39 teeth did not meet criteria for removal but had been scheduled for surgery. It was concluded that two-thirds of lower third molars not meeting NIH consensus criteria for surgery had been scheduled for removal. The reasons for this, which may include inappropriate criteria, require further research. PMID- 8357658 TI - Allergy to octyl gallate causing stomatitis. AB - Octyl gallate is an antioxidant (European Community number 311). It is used as a preservation agent in a wide variety of foods and other non-dietary substances. We report a case of a 49-year-old female with a 10-year history of 'burning mouth' and clinical erythema of the tongue, who, after investigation, proved to be allergic to octyl gallate. Management with an exclusion diet proved effective in both controlling the burning sensation and resolving the erythema of the tongue. PMID- 8357659 TI - Dentistry down-under. AB - It was with some trepidation that I entered into private practice in the City of Perth, Western Australia. I had left behind a collapsing NHS style of dentistry in England, where the average high street dentist has to work increasingly harder and faster to maintain the same salary, with barely time for luxuries such as leisurely consultations with patients or experimenting with new equipment or materials. PMID- 8357660 TI - Dental needs in Bosnia. AB - The dental needs of the growing number of refugees in Bosnia-Hercegovina were all too apparent on my recent visit to work with children in Medugorje in the Mostar province of Hercegovina. While this area has not undergone the sustained destruction of central Bosnia it is a natural first haven for refugees from the fighting. PMID- 8357661 TI - Peace of mind. PMID- 8357662 TI - Research in general practice. PMID- 8357663 TI - From crisis to crisis. PMID- 8357664 TI - Treatment of a dental phobic with pronounced aversion to rubber gloves by swallowing relaxation in two appointments. AB - This case illustrates where excessive dental stress on the swallowing reflex caused retching then nausea and eventually dental phobia. Swallowing relaxation enabled normal variable function to be quickly restored, which rapidly cured the phobia. PMID- 8357665 TI - What value market research? AB - Whether you have just left your hotel, purchased a new car or eaten at a roadside cafe, the chances are someone will have asked your views about their services, products and delivery. Why? Perhaps because the market oriented business knows better than to assume it understands its customers. A safer approach is to seek their views through market research, and that is the approach the new Quality Development Awards initiated by the BDJ, Denplan and Colgate have taken. PMID- 8357666 TI - 'Dentists and general'. PMID- 8357667 TI - 'Mercury spillage'. PMID- 8357668 TI - 'Revised guidelines for HIV-infected health care workers'. PMID- 8357669 TI - 'Personal orthodontic audit: the first 100 cases'. PMID- 8357670 TI - Non-setting pastes. PMID- 8357671 TI - An investigation into sugar-containing and sugar-free over-the-counter medicines stocked and recommended by pharmacists in the north western region of England. AB - Sugar-containing paediatric medicines can contribute to the aetiology of dental caries, and as many are sold over-the-counter (OTC) as are prescribed. This study evaluated a dental health education initiative among pharmacists in the north west of England in an effort to increase the sales of sugar-free preparations. It also investigated the stocks they held, their recommendations to their customers and their knowledge of, and attitudes to, sugar in medicine as a cause of dental caries. Following a baseline questionnaire, a randomly selected group of pharmacists were sent a dental health education leaflet informing them of the role of sugar-containing medicines in the aetiology of dental caries and a list of sugar-free alternatives which they were asked to stock and recommend. Twelve months later, a second questionnaire was completed by both the test and control groups of pharmacists. The most commonly stocked and recommended OTC paediatric medicines contained sugar. Of the 14 preparations stocked by over 90% of the pharmacists only two were sugar-free. During the year of the study the mean number of sugar-free medicines stocked by the pharmacists in the test group reduced from 7.70 to 7.12 (P < 0.05) and in the control group from 8.39 to 7.45 (P < 0.05). Seventy-seven per cent of the pharmacists thought that sugar in medicines could contribute to caries, but recommended sugar-containing preparations more frequently than sugar-free alternatives. The dental profession needs to actively promote medicines that are sugar-free if there is to be a change from the use of iatrogenic sugar-containing preparations. PMID- 8357672 TI - A follow-up study of incisor teeth which had been treated by apical closure and root filling. AB - A follow-up study was conducted of 93 non-vital immature incisor teeth treated by apical closure and root filling. Only six teeth had been lost and these losses were due to trauma, failed restorative treatment or root resorption. Life table analysis suggested that 86% of teeth would still be present after 5 years. The number of teeth at risk was too small after 5 years to provide precise enough estimates of the percentage of survivors. PMID- 8357673 TI - Panorama: a retrospect. PMID- 8357674 TI - Deafness and dentistry. AB - An article published last year in the British Medical Journal has illustrated that severe deafness does not preclude a career in medicine. My own experience and that of others prompts me to write that the same is true of dentistry. For patients who are deaf, dentists need to be aware of simple measures that may ease communication and avoid misunderstanding. PMID- 8357675 TI - 'Temporomandibular joint and orofacial pain'. PMID- 8357676 TI - 'A comparative study in the treatment of acute dentoalveolar infection'. PMID- 8357677 TI - Glass ionomer cement. PMID- 8357678 TI - A clinical trial of prostaglandin E2 in recurrent aphthous ulceration. AB - Thirty-five patients suffering from minor recurrent aphthous ulceration (RAU) entered a single-phase double-blind clinical trial of treatment with topical prostaglandin E2 (PGE2). The PGE2 was applied as a gel at a dose of 0.3 mg twice daily for 10 days. The vehicle alone acted as control. Patients were examined on days 1, 3, 5, 7 and 10 and also maintained daily diary cards. Of the 33 patients (94%) who completed the study, 18 had been allocated the active PGE2 and 15 the placebo. The two volunteers who failed to complete were excluded on technical grounds related to the strict study design and did not withdraw on the basis of adverse reactions to the trial preparation. Patients using the active PGE2 gel experienced significantly fewer new lesions than those on placebo (P < 0.05) over the 10-day trial period. There were no significant differences between the PGE2 and placebo gels in terms of speed of healing or pain relief of established aphthous ulcers. Prostaglandin E2 may, therefore, have useful prophylactic activity in RAU. PMID- 8357679 TI - A rare complication of dental treatment: Streptococcus oralis meningitis. AB - A case of Streptococcus oralis meningitis is reported. This followed extraction of a normal tooth during routine orthodontic treatment. No focus of infection could be demonstrated, either local to or distant from the extraction site. Full recovery followed hospital admission and intravenous benzyl penicillin. PMID- 8357680 TI - Dentistry and anaesthesia. PMID- 8357681 TI - 'Extended duties' orthodontic auxiliaries--an insight into the training and practice in America and Canada. PMID- 8357682 TI - Personnel auxiliary to dentistry. PMID- 8357683 TI - [Results of treatment of multiple ventral shoulder dislocation and surgical stabilization by Weber rotational osteotomy. 78th Annual Meeting of the Swiss Society of Trauma Surgery and Occupational Diseases 4-5 September 1992 in Olten]. AB - The treatment of recurrent anterior shoulder dislocation with the rotational humeral osteotomie by Weber showed best results in the follow-up of 53 operations when combined with a shortening of the capsule and the musculus subscapularis. Rotational humeral osteotomie alone showed in 20% redislocations. The rate of redislocation could significantly be reduced by additional shortening of the soft tissue. PMID- 8357685 TI - [Differential diagnosis and therapy of multi-fragment humeral head fracture--an analysis of three clinical studies]. AB - Out of the total number of patients of three Centers for Orthopaedic and Trauma Surgery, 93 comminuted humeral head fractures were clinically and radiologically controlled by means of a retrospective analysis. The classification of the fractures was made according to C.S. Neer, the clinical evaluation according to the Constant-Score. The analysis of the results in relation to the respective therapeutic methods revealed fundamental differences between the various types of fractures depending on the number of fragments. The prognosis of the three-part fractures appears essentially determined by the biomechanical conditions. This means that the therapeutic method has to be applied according to the restitution of the respective position of the fragments. Open reduction and internal fixation (mean Constant-Score 83 resp 91 points) or conservative treatment (78 points) seem to be primarily indicated in these cases. The prognosis of the four-part fractures, on the contrary, is largely determined by the problems of vascular supply of the head fragment, with a high risk of a humeral head necrosis. For this reason a primary prosthetic replacement (mean Constant-Score in case of primary implantation 75 points, compared with 54 points in case of conservative treatment and 52 points for open reduction and internal fixation), should be recommended for this type of fracture. For therapeutic and prognostic reasons, fractures at the proximal end of the humerus require an exact classification on the radiological basis of at least a so-called "trauma series". However, for a more accurate visualisation especially of the region of the lesser tuberosity (which is difficult to assess by means of conventional radiology), and consequently for the precise determination of the number of fracture-parts and their respective positions, we consider a CT Scan to be compulsory. PMID- 8357684 TI - [Fractures of the scapula and injuries of the acromioclavicular joint. The traumatized shoulder and its sequelae]. AB - Fractures of the scapula are rare and mainly result from a severe direct trauma. Most fractures may be treated non-operatively, only severely displaced and unstable fractures of the neck and/or the clavicula, unstable intraarticular fractures of the glenoid or open fractures (especially in combination with neurovascular lesions) should be fixed operatively. A dislocated fracture of the clavicula or glenoid should be approached first ventrally. Displaced fractures of the neck and body may also require an open reduction and fixation through a dorsal approach. Careful preoperative planning and anatomical studies are required to prevent intraoperative damage of innervation and vascularization. Cannulated single screws, 1/3 tubular plates or 3.5 LC-DC plates are recommended for the stable fixation of the scapula, whereas a Bosworth screw or a hook plate are helpful to stabilize the lateral clavicula and the acromioclavicular joint. Postoperative treatment: Temporary immobilization in a Gilchrist or Desault bandage for about 3 to 4 days thereafter careful passive and active mobilization. PMID- 8357686 TI - [Possibilities of shoulder arthroscopy in comparison with magnetic resonance tomography and arthro-computerized tomography]. AB - In the last 15 years the methods of examination of the shoulder have intensively expounded. According to a well documented retrospective study we describe the value of the shoulder arthroscopy and its correlation to MRI and arthro-CT findings. MRI represents nowadays the best way of exploring rotator cuff lesions and of investigating an impingement syndrome. Associated with a contrast medium its ability to clear up an anterior or posterior shoulder instability is now superior to the arthro-CT's. The arthroscopy allows the dynamic exploration of the joint and can be used not only as a diagnostic but also as a therapeutic procedure. PMID- 8357687 TI - [Long-term results of replacement of the head of the radius with a silastic prosthesis]. AB - 22 patients after head fracture were treated with replacement of the radial head by a silastic prosthesis. 11 patients were followed up after 91 +/- 48.8 months. The results are good to excellent. Twice a fracture of the prosthesis was detected at control. No prosthetic synovitis occurred in our patients. PMID- 8357688 TI - [The AO universal femur intramedullary nail: problems and their amelioration. Retrospective quality control study of 57 femur shaft fractures]. AB - Today intramedullary nailing is considered the treatment method of choice in fractures of the femoral diaphysis. In this retrospective quality control study 57 femoral fractures treated with the AO-Universal Femoral Nail have been reviewed. The average follow up time was 2.9 years. Intramedullary nailing was done as a primary procedure in 40 cases and in 17 cases as a secondary procedure following various initial operations. The results were evaluated according to the Stromsoe score. 27 of the 40 primary procedures went on to an uneventful healing and showed good to excellent final result. Technical errors (7), non-unions (4) and 1 deep infection required various secondary procedures. Thereafter the final number of good to excellent results amounted to 35 out of 40 patients. In the group with secondary i.m. nailing 9 out of 17 patients showed a good to excellent final result. 2 non unions persisted. In conclusion the AO-Universal Femoral Nail proved to be suited for the treatment of femoral shaft fractures for both primary and secondary procedures. In this series, however, technical imperfections led to a high rate of secondary procedures. Strict observation of the recommended operative technique is therefore mandatory. PMID- 8357689 TI - Effect of direct current stimulation on triradiate physeal cartilage. In vivo study in young rabbits. AB - Electrical stimulation with 8 microA direct current was applied to the triradiate physeal cartilage of young rabbits for periods of 3, 4, and 5 weeks. The effect was evaluated by morphometric measurement and histological observation. We tried to improve some previously described technical problems (e.g., movement of electrode during experiment) in this model of the growing acetabulum. Statistically significant differences in acetabular depth were found between the experimental and the control side in the 3-week group, but no obvious differences were found among the other measurements. Characteristic thickening of the growing physeal cartilage, especially proliferating cells, was found in the stimulated sides. Electricity affects the cell behavior in the triradiate physeal cartilage as well as the growth plate of long bone, but further study is still necessary to find more appropriate conditions to gain actual growth. PMID- 8357690 TI - Cellular and humoral immune responses after fresh meniscal allografts in mice. A preliminary report. AB - To date, no study of allogeneic meniscal transplantation has investigated both the host cellular immune response and the humoral immune response. Using inbred mice, we examined cellular immunity to meniscal allografts by assaying mixed lymphocyte culture and investigated humoral immunity through a complement dependent cytotoxicity test. The level of the stimulation index of the mixed lymphocyte culture seen after placing fresh meniscal allografts subcutaneously was not significantly higher than when isograft controls were similarly placed. Following placement of the allografts, no specific antibodies were detected in serum throughout the 24-week period after grafting. Thus, in mice, fresh meniscus apparently is not immunogenic. Our results tentatively suggest that a fresh allogeneic meniscus might be transplanted without any special treatment to decrease its immunogenicity. PMID- 8357691 TI - Allograft in the treatment of benign cystic lesions of bone. AB - Seventeen patients with benign cystic osseous lesions were treated by curettage and grafting using allogenic decalcified bone. Human bones were partially decalcified using 0.6 N HCl and preserved in 90% ethanol in a deep freezer at -16 degrees C. The cystic lesions were: 5 cases of fibrous dysplasia, 4 aneurysmal bone cysts, 3 simple bone cysts, 2 giant-cell tumours, 1 chondromyxoid fibroma, 1 non-ossifying fibroma and 1 fibrous cortical defect. The bones involved were: femur, tibia, humerus, fibula and calcaneum. Infection was a complication in three patients. In two of these it did not interfere with healing, but in one it persisted for more than 1 year with partial resorption of the graft. The time to adequate incorporation of the graft varied from 6 to 9 months in children and 9 to 15 months in adults. The overall response compares favourably with that to allograft from more sophisticated bone banks. PMID- 8357692 TI - Different healing patterns of experimental osteotomies treated by intramedullary nailing. AB - The healing of 52 diaphyseal osteotomies in rabbit tibiae was followed up histologically from 3 to 24 weeks after rigid intramedullary nailing. The histological evaluation was made from longitudinal sections through the osteotomy area. Particular attention was paid to the fracture healing pattern. A bulky periosteal response was visible in every specimen. At 24 weeks, the external callus was always well remodeled. The osteotomy line rapidly filled with bone from 6 weeks onwards. At 24 weeks, the site of osteotomy was detectable only on the basis of slight irregularity in the cortex. The secondary gap healing seen in 19 specimens was the most common type of bone union from 6 weeks onwards. In 13 specimens, the exact type of osteonal healing was not definable, since a solid union with good cortical reconstruction was always the final outcome. Altogether, four nonunions were detected throughout the study, none of these, however, in the specimens at 24 weeks. Considerable endosteal resorption was detected at 24 weeks, at which time at least one third of the original cortex had disappeared in all specimens. The rigid nail seems to ensure a relatively uneventful healing of the experimental osteotomies. Vast endosteal resorption and some nonunions make the use of medullary reaming in this connection doubtful. PMID- 8357693 TI - Foot and ankle fusions in Charcot-Marie-Tooth disease. AB - We reviewed 15 patients with Charcot-Marie-Tooth disease who were treated with foot or ankle fusions. Altogether, 26 feet were treated with fusions and the average follow-up time was 14 years. In half of the patients the principal symptom leading to fusion operation was instability of the ankle. In four patients, in two of them bilaterally, soft tissue corrections were performed before the fusion. In 21 cases, a subtalar triple arthrodesis was performed and each time correction to neutral position was the aim. In six feet, the triple arthrodesis was complemented by soft tissue plasties, e.g., plantar release, Achilles elongation, or transposition of tibial or peroneal tendons in order to achieve proper balance. Other primary fusions were a Grice-type fusion in one case, pantalar arthrodesis in one case, talocrural fusion in one case, and interphalangeal fusions in both feet in one patient with extreme claw foot. In four cases the triple arthrodesis failed to fuse (three nonunions and one delayed union), and new fusions were successful in three of them. The one pantalar fusion in the series was done for a 58-year-old man with late onset of the disease who had a very severe cavovarus deformity at the time of the operation, and this fusion failed to unite. In 17 of 26 feet, other operations than the primary fusion were performed, and five feet were operated on three or four times. In four feet the result was judged as excellent, in 15 good, in four fair, and in three poor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357694 TI - Usefulness of MRI in the preoperative diagnosis of cervical disk herniation. AB - We investigated the preoperative diagnostic value of MRI, myelography, and CT myelography (CTM) in a retrospective analysis of 17 patients (15 men and two women) who were surgically treated for cervical disk herniation. Their ages ranged from 29 to 63 years, with a mean of 49 years. Anterior interbody fusion using iliac bone grafts was performed following microscopic diskectomy in all patients. MRI, myelography, and CTM were performed in 13 patients, while four patients were operated on after MRI alone. Neurological improvement was observed in all 17 patients after the surgery. MRI proved useful for determining the level of symptomatic cervical disk herniation. Surgery can be carried out on the basis of MRI findings alone when there is disk herniation at a single level which corresponds with the patient's symptoms and signs. PMID- 8357695 TI - Acute torticollis in children due to atlanto-axial rotary fixation. AB - Acute, painful torticollis in a child is not uncommon. When no local changes can explain the disease, atlanto-axial rotary fixation should be considered. The position of the head is typical but the roentgenological diagnosis is difficult, and as early treatment is mandatory, it should be initiated even if the roentgenogram is "normal". We present a review of nine patients. PMID- 8357696 TI - Surgical treatment of acute type-V acromioclavicular injuries in athletes. AB - In a prospective study, 18 consecutive athletes with an acute type-V acromioclavicular sprain were treated with a coracoclavicular repair using a double velour Dacron graft. All patients were reviewed after a mean follow-up period of 6 years (range: 2-9 years). At follow-up, 12 patients (66.7%) showed a good or excellent result according to the Imatani evaluation system, and six patients (33.3%) demonstrated a fair or poor result according to the same system. Loss of reduction was encountered in eight shoulders (44.4%) despite an initial anatomical reduction. No correlation was seen between the overall scores at follow-up and the degree of residual dislocation, between the overall scores and the presence of coracoclavicular calcifications or ossifications, between the overall scores and the development of post-traumatic arthritic changes, or between the overall scores and the presence of osteolysis of the distal clavicle. PMID- 8357697 TI - Accelerometric assessment of osseous union. AB - Study of the dynamic structure response of the long bone has demonstrated the potential to provide an objective quantitative test of fracture healing. The method described consists of monitoring the propagation of a mechanical wave across the fracture site. This wave--generated by the fall of a steel ball from a constant height on a subcutaneous bony protuberance--was monitored on the side opposite the fracture gap by a light-weight accelerometer and traced on a beam storage oscilloscope. The signals received were found to correlate linearly with the different stages of the fracture welding, as shown by accepted clinical and radiological practice. It seems feasible that the method, being noninvasive, reproducible, simple, painless, and inexpensive, may be used to measure the parameters of fracture healing that are of clinical and scientific interest. PMID- 8357698 TI - Ulnar-shortening osteotomy after fracture of the distal radius. AB - The ulnar impingement syndrome due to a relatively long ulna is one of the complications of a fracture of the distal radius. We performed ten ulnar shortening osteotomies to restore distal radioulnar joint congruity. The mean relative ulna length was 4-5 mm. Insufficient bone healing was encountered in four osteotomies. Replating and cancellous bone grafting was necessary in two cases because of nonunion. The functional outcomes were good in six, fair in two, and poor in two cases. Nonunion and poor functional outcome were related to a malunion of the radius with a volar radiocarpal angle of 20 degrees or 25 degrees. It appeared that incongruity of the distal radioulnar joint favored nonunion. PMID- 8357699 TI - Traumatic anterior dislocation of the shoulder in a child. AB - Dislocation of the shoulder joint is a rare occurrence in children. This paper reports on traumatic anterior dislocation of the shoulder in a 3-year-old boy and a 9-year-old boy, together with a discussion of the relevant literature. PMID- 8357700 TI - Spontaneous regression of aneurysmal bone cyst. A case report. AB - Generally, aneurysmal bone cyst is considered to be a benign lesion that occurs rarely. Its etiology and treatment vary considerably, but curettage and grafting is the widely accepted treatment. Due to the nature of the disease recurrence is always expected. It rarely regresses and we report here a case that showed an improvement spontaneously after open biopsy. Follow-up for more than 4 years has shown no progression. PMID- 8357701 TI - High resolution EEG. PMID- 8357702 TI - The estimation of a realistic localization of dipole layers within the brain based on functional (EEG, MEG) and structural (MRI) data: a preliminary note. PMID- 8357703 TI - Models of source currents in the brain. AB - Electroencephalography (EEG) and magnetoencephalography (MEG) provide signals that are weighted integrals of source currents in the brain. In addition to technical aspects, the two methods differ in their sensitivities to various cerebral sources. Moreover, it is more difficult to determine the lead fields of EEG than of MEG. If it can be assumed that only one localized source is active at a particular time, the source location, direction, and amplitude can be found with the dipole model. However, if the assumption of a single localized source is violated, erroneous results are obtained. If a few sources are responsible for the measured fields, multiple-dipole models can be used. In the general case one must start from the fundamentals of estimation theory. The use of a priori information, together with experimental data, will provide the best possible solution to the inverse problem. In the case of minimal prior information, the so called minimum-norm solution is obtained. With the help of supplementary information, the resolution can be further improved. PMID- 8357704 TI - The influence of the volume conductor on electric source estimation. PMID- 8357705 TI - EEG/EP: new techniques. AB - The topographic analysis of electrical brain activity consists of the extraction of quantitative features which adequately describe the scalp recorded electrical fields of the brain. In the beginning of brain electrical activity mapping most methods centered mainly around the graphical display of multichannel EEG and evoked potential data. Meanwhile quantitative analysis strategies have been developed, and such methods are applied to topographic EEG and evoked potential data enabling the statistical evaluation of the effects of different experimental conditions as well as the comparison of various clinical populations. Major new analysis techniques comprise the computation of global field power and global dissimilarity for determination of components of evoked potential fields, the segmentation of map series by topographical features, time range analysis, FFT approximation for the spatial analysis of EEG frequency bands as well as correlation analysis and spatial principal components analysis (Spatial PCA). Data from experiments dealing with evoked brain activity will illustrate the application of these quantitative methods that also can be used for the analysis of the spontaneous EEG. PMID- 8357706 TI - MEG: new techniques. PMID- 8357707 TI - Equivalent dipole source localization of EEG and evoked potentials: sources of errors or sources with confidence? PMID- 8357709 TI - Magnetic source imaging based on the minimum-norm least-squares inverse. AB - The flow of ionic currents within the neurons of cerebral cortex produces a magnetic field that can be detected outside the human scalp. The dominant contribution is attributed to pyramidal cells, which are preferentially oriented perpendicular to the cortical surface. In general, it is not possible to deduce a unique representation of the spatial configuration of these cortical sources from a measurement of their field pattern alone. However, accurate a priori knowledge of the geometry of the underlying cerebral cortex makes it possible to infer the spatial configuration of these transcortical current sources, moment by moment, without imposing a simplified model such as a small set of current dipoles. To achieve such a realistic magnetic source image, we have introduced what we call the "Minimum-Norm Least-Squares Inverse" (MNLS inverse) for the magnetic problem. The MNLS inverse provides the least residual error in accounting for the measured field pattern, with a source current distribution having minimum power. An extension of this procedure provides an inverse solution for average field power, as opposed to field per se. This makes it possible to define spatial configurations of spontaneous cortical activity not phase-locked to a sensory stimulus. Rhythmic activity such as the occipital alpha rhythm is one example. Thus, it is possible to determine spatial patterns of enhanced or suppressed cortical rhythms that accompany cognitive processes and some pathological conditions. This paper provides the necessary background for understanding these recent developments, as well as examples of how they might be used. PMID- 8357708 TI - Comparison of high resolution EEG methods having different theoretical bases. AB - Mathematically simulated data is used to obtain direct comparisons of the accuracies of spline/Laplacian and cortical imaging algorithms in predicting cortical potential. Even though the two approaches have quite different theoretical bases, the two methods provide nearly identical estimates of cortical activity at scales greater than about 2 or 3 cm when 64 electrodes are used. PMID- 8357710 TI - Empirical bases for constraints in current-imaging algorithms. PMID- 8357711 TI - Magnetoencephalography using high temperature rf SQUIDs. AB - We have developed high-critical-temperature radio-frequency Super conducting QUantum Interference Devices (SQUIDs) with step-edge grain-boundary Josephson junctions and large flux focusers. These planar devices were fabricated from epitaxial YBa2Cu3O7 films and operated in the magnetometer and first-order gradiometer configurations while immersed in liquid nitrogen. At the temperature of 77K, we have attained a magnetic field resolution for the magnetometer better than 200 fT/Hz1/2 down to less than 1 Hz, i.e., over the low signal frequency range important for medical diagnostics. The results to date show a high promise for biomagnetic diagnostics. For the first time, we recorded the evoked responses from human brains using a high-temperature magnetometer and a first-order electronic gradiometer channel simultaneously. These results were obtained in a magnetically shielded room. An improvement in the magnetic field resolution by another order of magnitude is possible and probable. PMID- 8357712 TI - Topography and source analysis of brain activity associated with selective spatial attention and memory search. AB - We investigated the topographical aspects of the ERP reflections of visual spatial attention and memory search. Spatial attention was found to enhance the amplitudes of the P1 and N1 deflections. The brain activity in the P1-N1 latency range could be modeled with a single moving equivalent dipole, or alternatively with two stationary dipoles in a spatio-temporal dipole model. The dipoles were located in mesial and lateral posterior brain regions. Similar dipole solutions were obtained for ERPs to attended and unattended stimuli. Increasing the memory search requirements of the task resulted in an increase of late negativity, which was topographically distinguishable from the P3 component. PMID- 8357713 TI - EEG reactivity in high and low symptomatic schizophrenics, using source modelling in the frequency domain. AB - A dipole localization method in the frequency domain was used (FFT Dipole Approximation) to assess spatial differences in the spectral EEG reactivity (orienting response) between high and low symptomatic schizophrenics. Frequency bands of interest were determined empirically by comparing the two dichotomized patient groups with two matched control groups. Evidence for a correlation between EEG reactivity and severity of schizophrenic symptomatology was found, especially in the higher beta frequency range (16-25.5 Hz). Opposite effects were found in the two beta ranges of 20.5-22.5 Hz and 23.0-25.5 Hz, supporting the hypothesis that different EEG frequency bands have specific functional significances and that these bands are not necessarily those that are conventionally selected. PMID- 8357714 TI - Dynamic changes of alpha power as a probe of linguistic processes in normal and dyslexic children. PMID- 8357716 TI - Localization of topographic quantitative EEG in neurological disorders. PMID- 8357715 TI - Brain electrical correlates of psychological measures: strategies and problems. AB - We explore relationships between brain electrical activity and cognitive performance where qEEG data are correlated with psychological variables gathered at a different time. For a population of 202 healthy adults using univariate and multivariate correlation techniques in a split half replication design, we confirm prior findings that subjects with better psychological scores show shorter evoked potential (EP) latency, suggesting that speed of processing is an important factor in cognitive performance. By canonical correlation we demonstrate a consistent, replicable relationship between electrophysiological and behavioral data. We suggest that reliance upon univariate correlation may have fueled early controversies about relationships between electrophysiology and IQ. In addition we correlate psychological factors with the entire qEEG data set (both EP and spectral analyzed EEG) and demonstrate the use a multidimensional image graphics techniques to assist in visual assessment of the resulting correlation matrices. PMID- 8357717 TI - Models of brain sources. AB - Two categories of models are available for the functional imaging of scalp recorded electric brain activity: single-time-point and spatio-temporal. Instantaneous models require strict assumptions that do not conform with the underlying physiology, because they rely on the few voltage differences measured at only one sampling point. Spatio-temporal models create a spatial image of discrete multiple sources and a temporal image of source current wave forms which reflect the time course of the local activity in circumscribed brain areas at a macroscopic level. The spatial image may be limited in accuracy because it depends both on model and data, but it can be validated by scanning the brain with regional dipole sources. In many cases of temporal lobe epilepsy, for example, interictal spikes can be described adequately by as few as two equivalent dipoles, which image the vertical source current arising from the medio-basal aspect of the temporal lobe and the horizontal source current from its lateral surface. PMID- 8357718 TI - Clinical applications of MEG in epilepsy. PMID- 8357719 TI - Expectancy revisited. PMID- 8357720 TI - CHIRBASE, a graphical molecular database on the separation of enantiomers by liquid-, supercritical fluid-, and gas chromatography. AB - In order to cope with the increasing number of publications on the separation of enantiomers by chromatography on a chiral stationary phase, the graphical molecular database CHIRBASE was created. In the present state, the database package covers information (structural, bibliographic, and chromatographic data) on liquid-, supercritical fluid-, and gas chromatography; other methods will follow. CHIRBASE, running on the MDL software Chembase, meets the requirements of contemporary information management in the chemical and pharmaceutical industry. (Detailed information including a demo-version of each part of CHIRBASE can be obtained from the authors on request). PMID- 8357721 TI - [Incentives and competition mechanisms]. PMID- 8357722 TI - [Neuroblastoma in childhood. Review of clinical aspects and of 2 forms of treatment]. AB - The optimum time for a surgical resection of the primary lesion in the advanced neuroblastoma has not been defined properly. Recently the therapeutic results of the advanced neuroblastoma have improved through the use of preoperative chemotherapy. We check on our patients who were affected by this disease in the last 15 years. From 185 malignant tumours diagnosed in our department, 52 belonged to neuroblastomas with more than 12 months of evolution. Most of them were diagnosed during the year after their birth and it was not observed a difference of sexes. The location was the habitual one, except 2 cases of thoracoabdominal tumour and 1 of stesioneuroblastoma the most common manifestation was the metastatic disease. Catecholamines in 24 hours urine were positive in 74% of our patients, and enolase in 100% of the same ones. The longest percentage of patients is distributed in the advanced stages of Evans. PMID- 8357723 TI - [Complications of the use of implantable reservoirs of central venous access++ in pediatrics: causes and treatment]. AB - The use of a totally implantable reservoir venous system (RIAV) in children improved the quality of life of a large group of patients undergoing long-term drug therapy. We have routinely used RIAV in the last four years with specific therapeutic indications. One hundred and seven Low Profile model Port-a-Cath (PAC) and two PAS-Port were followed in 104 patients, for a total of 43.000 days, i.e. 395 days per system. Complications which arose in our series were classified as severe (requiring system withdrawal) and slight (resolved medically). There were 17 severe complications: 9 obstructions, 5 infections, 2 skin necrosis and 1 catheter roture, and 5 slight complications including 2 obstructions, 2 system infections and 1 haematoma. Analysis of complications provided the experience necessary to establish a protocol, in order to reduce the number of catheter withdrawals to a minimum. PMID- 8357724 TI - [Biliary complications in hepatic transplantation in children]. AB - Biliary reconstruction continuous to be a source of severe complications in paediatric liver transplantation (PLT). Five (7%) biliary complications in 70 PLT in patients aged from 8 months to 13 years with a body weight of 4-37 Kg. were studied. End-to-end common duct anastomosis (group I) with Kehr drainage was performed in 18 cases. End-to-side common duct jejunostomy (group II) was performed in the remaining 52 cases. In this group, two patients were found to have stenosis and biliary stones or sludge respectively and one obstruction with sludge without evident stenosis. All cases required surgery and there was no mortality. Transparietohepatic cholangiography has provided early diagnosis of these complications and has proved to be a reliable method of choice. The use of inert biological material in Kher tubes and steroids slow down the organization of a fistulous tract, thereby causing the complications which arose in group I. PMID- 8357725 TI - [Barrett++ esophagus in children. Presentation of 12 cases]. AB - This paper describes 12 cases of Barrett's oesophagus selected out of a population of 364 refluxing children studied from 1986 to 1990. Their mean age was 14, seven were cared for in special institutions for brain damaged and 2 had been operated upon for oesophageal atresia at birth. Excessive acid exposure was documented in 8/10 patient studied and simultaneous gastric and oesophageal pH monitoring demonstrated massive duodeno-gastric alkaline reflux in 3. Histological studies revealed that columnar-lined epithelium was of fundic type in 2 cases, of junctional type in 7 and of specialized type in three. Helicobacter pylori was found in the mucosa of 8 patients. The present series confirms that BE should be looked for endoscopically in children with GER and provides further evidence of the long duration of GER disease and the excessive acid-alkaline chemical exposure of the oesophageal lining in the pathogenesis of mucosal changes. PMID- 8357726 TI - [Treatment of colonic atresia. Report of 3 cases]. AB - Atresia of the colon (AC) is an uncommon cause of neonatal intestinal obstruction requiring prompt surgery. However, its optimal operative management is matter of discussion. We report the surgical therapy and evolution of three cases successfully treated at our department. A type I case was submitted to a coloplasty plus resection of the diaphragm; two cases of type III underwent a two staged procedure, i.e., colostomy with subsequent anastomosis without resection. After analysing the different operative procedures we suggest that a colostomy with later establishment of intestinal continuity may be an advantageous procedure even in the healthy patients with proximal lesions. A coloplasty is a safe alternative to type I atresias. PMID- 8357727 TI - [Bladder psoas hitch. Report of 11 cases]. AB - Bladder psoas hitch is an surgical technique which, in very complicated cases, like repeated failures of vesico-ureteral re-implants or undiversions, allow us to bridge the shortness of the ureter and obtain a good vesico-ureteral reimplant. The surgical maneuver is described and several of the 11 cases operated by this technique are commented. The results are presented. PMID- 8357728 TI - [Airway obstruction associated with gastroesophageal reflux: experimental study]. AB - Gastro-oesophageal reflux (GER) frequently complicates the clinical course of children suffering from conditions leading to upper airway obstruction (UAO) (choanal atresia, tracheomalacia, oesophageal atresia, vascular rings etc.). In an attempt to explore whether partial airway obstruction causes changes in the normal thoraco-abdominal pressure gradients, we measured end-inspiratory intrathoracic and intra-abdominal pressures in anesthesized rats under spontaneous breathing conditions, after tracheostomy and under upper airway obstruction induced by tracheal intubation with three progressively narrower cannulae (inner diameters 1.0 mm, 0.5 mm. and 0.2 mm.). We also measured the lower oesophageal sphincter pressure (LESP) and length (LESL) and calculated the thoraco-abdominal end-inspiratory pressure gradient (TAEIPG). Neither LESP nor LESL changed significantly before or after maximal tracheal obstruction but TAEIPG significantly increased from 5.58 +/- 1.34 cm H2O to 17.62 +/- 4.27 cm. H2O (p < 0.01) under the same conditions, mainly as a result of progressively stronger intra-thoracic pressures during inspiration. These experiments prove that the powerful thoraco-abdominal pressure gradients developed after partial UAO may contribute to the pathogenesis of GER by overcoming the anti-reflux barrier function. PMID- 8357729 TI - [Neonatal tracheomalacia. Study of 3 cases treated with aortopexy+]. AB - Neonatal tracheomalacia is a disease in which there is a softening of the tracheal wall with lost of this consistency. This cause expiratory collapse cough and respiratory difficulty it is generally associated with Esophageal atresia and Vascular Rings. Exceptionally is a primary disease. In this paper we present three cases of neonatal tracheomalacia treated by aortopexy who is at the moment the best treatment that we have in severe cases. Soft cases will remit with conservative treatment. PMID- 8357730 TI - [Paraplegia following surgical repair of a ductus and of a coarctation of the aorta in childhood]. AB - The cases of two girls with 4 and 7 years of age presented. They had a patent ductus and an aortic coarcation which were subsequently surgically repaired. After the operation paraplegia was diagnosed. With rehabilitation they are able to walk, however paraparexis persist. Anatomy of the arterial irrigation of the spinal cord is reviewed and also the pathophysiology and mechanisms of medullar ischemia. PMID- 8357731 TI - [Cerebral abscess secondary to esophageal dilatations]. AB - We report two cases of cerebral abscess secondary to esophageal dilations in children with caustic stenosis of the esophagus. High fever and neurological findings postdilation lead us to suspect this complication. Cranial C.T. confirmed the diagnosis. Clinical course was favourable in both patients, with antibioterapy on the first case and combined therapy with surgical drainage and parenteral antibiotics on the second patient. We remark the importance of suspect this complication on the basis of clinical and tomographic findings on the pediatric patients subjected to esophageal dilations. Pathogenic ways of bacterial dissemination from the esophagus to the brain are discussed and reviewed. PMID- 8357732 TI - [Intestinal obstruction caused by milk curds in newborns]. AB - Intestinal obstruction due to milk curds syndrome may present with a clinical picture and radiological findings which suggest the correct diagnosis. This type of intestinal obstruction usually affects neonates, previously healthy, with concentrated formula feeding. Surgical treatment may be avoided in some cases by the administration of Gastrografin enemas. Two patients with milk curd obstruction treatment in our Hospital, are presented. PMID- 8357733 TI - [Hemi-splenectomy in epidermoid cyst of the spleen. Presentation of a case]. AB - We report a case of non-parasitic splenic cyst, diagnosed by abdominal ultrasound scan. These were treated by partial splenectomy. The anatomopathological study indicated the existence of epithelial coating. PMID- 8357735 TI - [European board of pediatric surgery]. PMID- 8357736 TI - Spondyloarthropathies. PMID- 8357734 TI - [Solitary intestinal fibromatosis: an unusual cause of neonatal intestinal obstruction]. AB - We report a new case of solitary intestinal fibromatosis (SIF) in a neonate with intestinal obstruction in the first day of life. At the laparotomy was found to be due to a solid mass in the jejunum. A segmental jejunal resection with anastomosis was performed. Histologic examination showed a SIF. The postoperative course was excellent in contrast to cases of congenital fibromatosis with multiples lesions, which carries a poor prognosis. PMID- 8357737 TI - Clinical features and management of ankylosing spondylitis. AB - The clinical features and management of ankylosing spondylitis are reviewed here. Important descriptions of the paleopathology of ankylosing spondylitis are discussed, and articles are reviewed in which the characteristics of some extra articular complications are described. Controversy persists on the bone mineral content of patients with ankylosing spondylitis and its relationship with disease duration and outcome, as well as on the role of sulfasalazine in the management of ankylosing spondylitis. PMID- 8357738 TI - Infectious agents in reactive arthritis. AB - It is now clear that the deposition and persistence of bacterial antigens in the joint are significant features of reactive arthritis. It is possible that in some instances this represents persistence of live bacteria, and several studies point to the potential value of antimicrobial therapy. Searches for bacterial DNA and RNA have yielded conflicting data, however, so further developments in this area will be of great importance. It is likely that bacterial antigens interact in some way with class I major histocompatibility complex (MHC) antigens in the pathogenesis of reactive arthritis. However, with the increasing understanding of the structure and function of HLA molecules, some evidence of a classic antigen class I MHC-CD8 T-lymphocyte interaction is now emerging. Thus far, the mechanisms that link HLA-B27 and bacterial antigens with reactive arthritis remain unclear. PMID- 8357739 TI - Psoriatic arthritis and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome. AB - Psoriatic arthritis is an inflammatory arthropathy associated with psoriasis, and its clinical presentation varies from case to case. Distal interphalangeal involvement is characteristic but not seen in all patients. Enthesopathy, including that of the spine, is common and contributes to the classification of psoriatic arthritis as a seronegative spondyloarthropathy. The etiopathogenesis of psoriatic arthritis is not well understood, and evolution as measured by follow-up is variable. Treatment includes nonsteroidal anti-inflammatory drugs and some of the drugs used in the treatment of rheumatoid arthritis. Sulfasalazine and, in the more severe cases, cyclosporine, are being studied for efficacy and tolerance. Some cases of psoriatic arthritis are associated with an inflammatory bone disease, frequently seen on the anterior chest wall, which is part of the newly described SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. SAPHO syndrome is characterized by this bone involvement, which can affect the spine and peripheral bones. Various skin conditions are associated with this syndrome, but they do not necessarily occur in all cases. Chronic recurrent multifocal osteomyelitis, which is seen mostly in children, may be a presentation of SAPHO syndrome. Associations with sacroiliitis, bowel disease, and psoriasis link SAPHO syndrome with the spondyloarthropathies. PMID- 8357740 TI - Immunogenetics of the spondyloarthropathies. AB - In this review, recent data relevant to better understanding of the immunogenetics of the spondyloarthropathies are discussed or, in a somewhat broader sense, the HLA-B27 disease associations. Although in 1993 much more is known about the B27 molecule than was known in 1992, its contribution to the pathogenesis of disease is unclear. Peptide presentation to the T-cell receptor is still the basic, if not the only, function of HLA class I molecules. Nothing special was found for the B27 gene, molecule assembly, protein sequence, and crystal and peptide-binding motif, nor for the function dependent on these physical properties. Nevertheless, the theory regarding an "arthritogenic peptide" seemed to promise an explanation. However, this theory is rather an assembly of older views modified by the new data and is missing any detail or perspective that would answer the specific question: why B27 and not other HLA molecule(s)? If the solution is simple, and B27 is qualified to bind certain (bacterial) peptides that are not bound by any other class I molecule, or the unique complex, B27 + x, has special properties resulting in a "dysfunction," there is still no answer to the question: which peptide and why does its binding with B27 result in disease? PMID- 8357741 TI - Bacterial arthritis. AB - The 1992 literature on septic arthritis reiterated the factors that portend a poor outcome in septic arthritis. However, we still know very little about how to improve the outcome for such patients. Infections of the musculoskeletal system may be more common among patients with HIV than the reported cases indicate. Bacterial endocarditis is frequently associated with musculoskeletal complaints. Low back pain may be a presenting manifestation. Acute gout and septic arthritis can cause peripheral arthritis in some patients with bacterial endocarditis. Septic arthritis can present unusual manifestations and can occur as a complication of arthroscopic surgery; the risk factors for its development after arthroscopy have been identified. Arthroscopy as a therapeutic procedure to drain an infected joint is discussed. PMID- 8357743 TI - Reactive arthropathy and autoimmunity in non-HIV-associated immunodeficiency. AB - The spectrum of arthropathy in non-HIV immune deficiency states includes arthritis due to prevalent infectious pathogens and autoimmunity that may in some instances be triggered by microorganisms. Joint symptoms may be clinical manifestations of disease, or they may develop later during therapy for immunodeficiency. Pathogenesis can be related to occult infection, loss of mucosal barrier function, defective clearance of immune complexes, or aberrant immune responses. Proper treatment includes an appreciation of likely pathogens, an understanding of the nature of immunologic deficits, and rigorous exclusion of immune dysfunction that may be secondary to treatment. PMID- 8357742 TI - Infections complicating joint replacement and other orthopedic conditions. AB - The principles underlying the diagnosis and management of infection in the orthopedic patient are well established. Despite this, the patient with an infected implant still presents the orthopedic surgeon with a challenging problem. In this review, I consider the recent developments in the diagnosis and management of the infected arthroplasty, infected tibial nonunions, spinal infections, and disease transmission by bone allografts. PMID- 8357744 TI - Osteoarthritis and crystal deposition diseases. PMID- 8357745 TI - Management of osteoarthritis of the hip and knee joints. AB - Osteoarthritides of the hip and knee represent two of the most important causes of pain and physical disability in the community. Recent studies have helped delineate the different patterns, rates of progression, and determinants of outcome in these two conditions. For example, patellofemoral and tibiofemoral osteoarthritis of the knee appear to have different associations and consequences; psychosocial factors and muscle strength seem to be the key determinants of pain and disability. These insights have contributed to a parallel development in new treatment strategies for established hip and knee osteoarthritis, including increased psychosocial support, educational and fitness programs, and different drugs and physical interventions. Therapeutic regimens geared to the specific needs of patients with lower limb osteoarthritis are emerging. They should replace the inappropriate application of treatments designed for inflammatory arthropathies to patients with osteoarthritis. PMID- 8357746 TI - Imaging in osteoarthritis and crystal deposition diseases. AB - The challenge in imaging joints and articular cartilage is to detect both early and subtle changes that may influence the treatment of osteoarthritis and crystal deposition diseases. Although radiographs show gross changes, they cannot show cartilage surfaces directly. Both ultrasonography and magnetic resonance imaging are able to demonstrate both the surface and internal details of articular cartilage. Advances in magnetic resonance imaging have begun to show internal details of articular cartilage that correspond with histologic zones. These changes can be shown using minor modifications of conventional imaging techniques. More elaborate studies using experimental contrast agents and sodium nuclear magnetic resonance imaging have shown changes in the magnetic resonance signal intensity that appear to correlate with the distribution of proteoglycans in the cartilage matrix. The application of these techniques may be possible in a clinical setting to enhance the detection and monitor the changes of degenerative joint disease. PMID- 8357747 TI - Gout and mechanisms of crystal-induced inflammation. AB - Since last year's review of gout and hyperuricemia, investigators have described new potential mechanisms that may contribute to urate crystal deposition and the propagation, self-limitation, and therapeutic control of gouty inflammation. The clinical presentation of gout in women continues to be described in greater detail. Also, new information on oral allopurinol desensitization is now available to help approach the difficult problem of allopurinol hypersensitivity. PMID- 8357749 TI - Epidemic neuropathy in Cuba. PMID- 8357748 TI - Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases. AB - Recent advances in understanding the pathogenesis and mechanisms of tissue damage related to calcium-containing crystals are highlighted in this review. The clinical spectrum of diseases related to crystal deposition has broadened and includes distinct neurologic syndromes associated with hypertrophy and calcification of the ligamentum flavum or posterior longitudinal ligament in the cervical spine. Diagnostic methods of crystal identification are also reviewed. PMID- 8357750 TI - Evaluation of epidemiology course in Haiti. PMID- 8357751 TI - Tracing infection by T. cruzi in El Salvador. PMID- 8357752 TI - Selective media for detecting and enumerating foodborne yeasts. AB - No one medium is satisfactory for detecting, isolating and enumerating all yeasts in all foods. Antibiotic-supplemented media such as dichloran rose Bengal chloramphenicol agar, tryptone glucose yeast extract chloramphenicol agar, oxytetracycline glucose yeast extract agar and rose Bengal chloramphenicol agar are superior to acidified potato dextrose agar and other acidified media for enumeration of the vast majority of spoilage yeasts. Dichloran glycerol (18%) agar performs well for enumerating moderately xerotolerant yeasts. Malt extract yeast extract glucose (up to 60%) can be used for detecting and enumerating moderate and extreme xerophiles. These media also support the growth of moulds. Lysine agar, Schwarz differential agar and Lin's wild yeast differential agar are used by the brewing industry to differentiate wild yeasts from brewer's strains. Lysine agar is selective for apiculate yeasts and ethanol sulfite yeast extract agar is selective for Saccharomyces. Both have application in wineries. Modified molybdate agar can be used to selectively isolate yeasts from tropical fruits. Preservative-resistant yeasts can be detected on malt acetic agar. The recommended incubation temperature is 25 degrees C, but incubation time between plating and counting colonies ranges from 5 days for determination of general populations of yeasts to 10 days for more for xerotolerant yeasts. There is need for new and improved media for selectively isolating various groups, genera, species and strains of yeasts capable of growing only under specific environmental conditions in specific types of foods and beverages. PMID- 8357754 TI - Methods for the separation of yeast cells from the surfaces of processed, frozen foods. AB - More aggressive pre-isolation treatments of samples, such as vigorous shaking, jet-streaming with excess of water and sonication, were applied in sequence to the study of yeast ecology of the surface of several frozen foods. The conventional isolation method based on bland shaking was unable to disengage yeast cells from their substrates in most of the cases, while each more aggressive treatment caused progressive separation of colony-forming units (cfu) along the sequence of application of the three procedures. Altogether, in the majority of cases, a few colony forming units were found on the surface of frozen fish, poultry, vegetables and mushrooms. Conversely, the numerically poor yeast flora is almost constantly represented by many species, always different from those found on the surface of the same foods in nature before processing. The uniformity of the composition of the yeast flora throughout the four different categories of foods excludes any possible occasional origin of the yeast colonization and probably indicates a processing plant origin. PMID- 8357753 TI - Simplified techniques for identifying foodborne yeasts. AB - Four problematic areas associated with the identification of foodborne yeasts are discussed. These consist of (1) the inability of conventional identification tests to recognize some common and important foodborne yeasts characterized by genomic differences (e.g., Saccharomyces cerevisiae, S. bayanus and S. pastorianus); (2) the delay in application of non-traditional identification methods such as DNA fingerprinting, chromosome karyotyping, protein electrophoretic patterns and fatty acid profiles for routine identification purposes; (3) the lack of commercially available manual or automated identification systems dedicated to the diagnosis of foodborne yeasts; and (4) the disregard for considering ecological frequency of yeasts in computerized probabilistic identification systems. PMID- 8357755 TI - Application of fatty acid profiles in the identification of yeasts. AB - In order to develop a rapid yeast identification technique using fatty acid profiles, an extensive survey has been conducted in our laboratory on the long chain fatty acid composition (CLFAC) of yeasts representing the endomycetous and basidiomycetous yeast domain. It was accomplished by cultivating the yeast strains under standardized conditions in a synthetic liquid medium. When stationary phase was reached the cells of each culture were freeze-dried and the CLFAC was examined by gas chromatography. It was found that the fatty acid profile obtained for each strain was reproducible. However, as work progressed, it became clear that variation exists within species and that the relative percentages of some strains from different species may overlap. Identification of species could therefore not be achieved in all attempts, even when the resolution of the fatty acid analyses was enhanced by using capillary columns, useful for the detection of minor fatty acids. When used in isolation, CLFAC analyses is therefore not a generally applicable identification technique for yeast species. However, the technique was found to be a valuable chemotaxanomical tool to distinguish between strains of certain species, species of certain genera and species from particular environments. The technique currently finds application in the South African food and beverage industry as a quick, cheap and easy way to distinguish between strains of Saccharomyces cerevisiae. It is also used by an industry which produces bioprotein from Geotrichum candidum, to determine fungal contaminants in a quality control process. PMID- 8357756 TI - Immuno-assay techniques for detecting yeasts in foods. AB - A brief literature review on immuno-assay of yeast cell wall antigens is given. Special attention is paid to extracellular, thermostable yeast antigens (EPS), which are released to the growth medium by many yeast species. The EPS of Saccharomyces cerevisiae and of Stephanoascus ciferrii (syn. Candida ciferrii) could be specifically and sensitively detected by a sandwich ELISA, using an IgG raised in rabbits immunized with the EPS of these yeasts. The EPS ELISA of three basidiomycetous yeasts tested was not specific, that of Geotrichum candidum was genus-specific but was not sensitive. The EPS of Zygosaccharomyces bailii could be detected in a highly specific competitive ELISA but not in a sandwich ELISA or in a latex agglutination test. PMID- 8357758 TI - Children have a right to AIDS facts. PMID- 8357757 TI - Use of electrophoretic karyotyping and DNA-DNA hybridization in yeast identification. AB - Contour-clamped homogeneous electric field (CHEF) gel electrophoresis was used to separate intact, chromosome-size DNA of different species of Saccharomyces and Zygosaccharomyces. Strains of the same Saccharomyces species had similar electrophoretic karyotypes. However, reproducible differences between individual bands indicated that strain-specific chromosome length polymorphism (CLP) is widely spread in these organisms. Strains of Zygosaccharomyces spp. showed karyotype differences beyond chromosome length polymorphism. A new, DNA-DNA hybridization technique was developed to test conspecificity, using individual chromosomes as templates to prepare randomly primed, radioactive probes. Under our conditions of stringency, species and chromosome-specific hybridization reactions were achieved with these probes. Using isolated chromosomes of Sacch. cerevisiae, Sacch. bayanus, and Zygosacch. rouxii as templates for probe preparation, conspecificity of strains was established, and closely related yeast species were distinguished with high reproducibility. This method is an efficient tool for studying genetic diversity of a given yeast species. Also, it can assist in yeast species identification and taxonomy. PMID- 8357759 TI - HIV health education needs reassessing. PMID- 8357760 TI - Behind the headlines: death by waiting list? PMID- 8357761 TI - Community health: a brush with bureaucracy. Interview by Maura Thompson. PMID- 8357762 TI - Organ donation: a gift of life. Interview by Simon Canning. PMID- 8357763 TI - Setting standards in diabetes education. AB - The project described in this article was undertaken to develop and improve the levels of nursing knowledge on diabetes mellitus and subsequently improve the quality of patient education on diabetes. A written standard on health education was devised and an educational programme for nurses was implemented to prepare nurses to meet the requirements of the standard. The project is ongoing, and initial results suggest that while there have been problems, nurses appear to be more confident in assuming their roles as patient educators. PMID- 8357764 TI - Job opportunities: growth or decline? AB - If and when those much promised green shoots of economic recovery start sprouting, the effect on nursing remains open to question. The growth in general unemployment has tailed off, but nurses are increasingly concerned about their own future employment prospects. This article discusses whether career opportunities look set to improve or diminish beyond mid-decade. PMID- 8357765 TI - Statistical tests (Part 1): Descriptive statistics. AB - This series of three articles has been designed to facilitate an understanding of some commonly used statistical terms encountered when reading research articles. In addition, it is hoped that the nurse researcher who has access to a personal computer containing basic statistical software will gain some insight into which statistical tests to use and in what circumstances. The articles do not attempt to provide any understanding of the mathematics of the statistical tests employed. PMID- 8357766 TI - Helping male victims of sexual abuse. AB - The author recounts his experience of working in an extra care psychiatric unit in which a proportion of the male attenders had been subject to sexual abuse as children. While there is a paucity of literature on the subject of male sexual abuse, his experience of looking after victims suggests that many commonalities with female sexual abuse survivors exist. A model is presented as guidance for practitioners in helping men who have suffered sexual abuse as children. PMID- 8357767 TI - Up and away. The Barry Clifton column. PMID- 8357768 TI - Sister Susie. Susie goes grammy bashing. PMID- 8357769 TI - A matter of Trust. Interview by Trevor Clay. PMID- 8357770 TI - Size and moans. PMID- 8357771 TI - Workwise: banking on work. PMID- 8357772 TI - One minute wisdom. PMID- 8357773 TI - Hypertensive labeling: does it have therapeutic implications. AB - Screening for hypertension within the proper setting potentially leads to the detection of numerous (mild) hypertensives, some of whom in due time may well qualify for treatment. One disadvantage of the procedure appears to be that hitherto unwitting hypertensives may develop some adverse psychological and physiological phenomena. Behavioral effects seem to be particularly obvious after screening on the worksite, where newly identified hypertensive employees tend to respond with increased absenteeism and allied symptoms of labeling. In the clinical setting, physiological studies in recently informed hypertensives have demonstrated a series of signs of increased sympathetic activity: heart rate, cardiac index, circulating catecholamines, and renin, and even blood pressure itself, tend to be higher in aware vs. unaware young hypertensives. Although some correlations between psychological and physiological sequelae have been observed, the true nature of such links is far from clear. Simple anxiety does not seem to be the main mechanism. Pending further research, the question is discussed as to whether these phenomena are harmful enough to warrant a need for counseling or treatment. PMID- 8357774 TI - Effects of the single and repeated administration of benazepril on systemic and forearm circulation and cardiac function in hypertensive patients. AB - The hemodynamic and cardiac effects of the new angiotensin-converting enzyme inhibitor, benazepril, were studied in 28 hypertensives in a double blind, placebo-controlled, between-patient study. Hemodynamic studies were performed noninvasively by means of M-mode echo (central hemodynamics and left ventricular systolic function), 2-D echo-Doppler (left ventricular diastolic function), and pulsed Doppler flowmetry (forearm circulation). Examinations were done at the end of a placebo run-in period and 3 hours after benazepril administration, both on the first day and after 6 weeks of treatment (10 or 20 mg once daily, according to patient response). In comparison with placebo, benazepril reduced systolic (p = 0.04) and diastolic (p = 0.003) blood pressure, because of a significant reduction in systemic vascular resistance (p = 0.03), while cardiac output was unchanged. Forearm vascular resistance was reduced and brachial artery compliance increased, although not to a statistically significant level (both p = 0.07). Both systolic and diastolic left ventricular function were positively influenced by the afterload reduction: End-systolic stress was reduced by 12% (p = 0.07), as was the late diastolic peak flow velocity (p = 0.02). All hemodynamic changes were evident after acute benazepril administration, and no differences was observed between acute and repeated treatment. We conclude that, similar to other ACE-inhibitors, benazepril reduces blood pressure through a reduction in vascular resistance, while cardiac output and heart rate are unaffected. These hemodynamic effects occur as early as after the first administration and exert a favorable influence on left ventricular dynamics. PMID- 8357775 TI - Arrhythmogenicity of antiarrhythmic drugs and intraventricular conduction disorders: possible aggravation by myocardial ischemia--study in the porcine in situ heart. AB - The effects of three antiarrhythmic drugs were investigated in anesthetized, open chest pigs, in a left ventricular area, under pacing at a constant high rate (180 beats/min), in the absence and presence of ischemia. Ischemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin. In addition to the surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibers. In the absence of ischemia, intravenous flecainide and propafenone 2.5 mg/kg, and intravenous cibenzoline 2.0 mg/kg considerably lengthened conduction time (by 50 90%) but had no significant effect on the monophasic action potential duration. Consequently, the cited antiarrhythmic drugs enhance the prolongation of conduction time by 60% but do not limit the 30% shortening of the monophasic action potential caused by ischemia. Contrary to what was expected, they largely reduced the time to onset of the fibrillation due to ischemia from about 120 to 25 seconds. Thus, they manifested profibrillatory properties (more pronounced than those of other antiarrhythmic drugs of class I), which might be explained by their potent action on depolarization. PMID- 8357776 TI - Attenuation of reperfusion-induced ventricular fibrillation in the rat isolated hypertrophied heart by preischemic diltiazem treatment. AB - The ability of the calcium antagonist diltiazem to protect against reperfusion induced arrhythmias in hypertrophied myocardium was studied. Hearts from normotensive and DOCA-salt hypertensive rats were Langendorff perfused and subjected to 10 minutes of stabilization, 10 minutes of left coronary artery occlusion, and 5 minutes of reperfusion. The incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion were determined and the effects of diltiazem or vehicle (given as a single bolus 3 minutes before coronary artery occlusion) were assessed in hypertrophied and normal hearts. In vehicle-treated (control) hypertrophied hearts, VF incidence was 91% compared with 67% in normal hearts, and the median duration of VF was 272 seconds (mean 207.4 +/- 32.3) compared with 27 seconds (mean 110.6 +/- 36.6; p < 0.05), respectively, suggesting that reperfusion VF is more severe in hypertrophied hearts. In normal hearts, diltiazem 18 micrograms reduced VT incidence from 92% to 55%, reduced VF from 67% to 27%, and sustained VF from 42% to 9%. In hypertrophied hearts, 18 micrograms diltiazem reduced the VT incidence from 100% to 58%, reduced VF from 91% to 25% (p < 0.01), and sustained VF from 82% to 8% (p < 0.01). Median VF duration in this group was reduced to 0 seconds (p < 0.05; mean 24.7 +/- 22.6). Diltiazem did not significantly affect heart rate or coronary flow rate decreases during ischemia. However, developed tension, at the onset of ischemia, was lower in diltiazem-treated groups than in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357777 TI - Actions and interactions of E-4031 and tedisamil on reperfusion-induced arrhythmias and QT interval in rat in vivo. AB - The effects of the Ito blocker, tedisamil (0.1, 1.0, and 3.0 mg/kg, IV), and the IK blocker, E-4031 (0.1, 1.0, and 3.0 mg/kg, IV), on the incidence and duration of reperfusion-induced arrhythmias were compared in the anesthetized rat (n = 12 per group). Reperfusion arrhythmias were evaluated after a 5 minute occlusion period of the left main coronary artery. In the absence of any pronounced effect on blood pressure, tedisamil and E-4031 reduced heart rate in a dose-dependent manner. During the preischemic period, QTc interval was increased by tedisamil but was not changed by E-4031. Both compounds increased the QTc interval during the ischemic period and also during the reperfusion. E-4031 was unable to reduce the incidence and duration of reperfusion-induced ventricular arrhythmias after 5 minutes of coronary artery occlusion. Tedisamil dose-dependently reduced the duration of reperfusion arrhythmias and their incidence. In a second set of experiments, the combination of tedisamil (1.0 mg/kg) with E-4031 (1.0 mg/kg) was administered. The electrocardiographic action of this combination was similar to that observed with tedisamil given alone. However, with the combination the incidence of fibrillation was reduced from 83% in the control group to 8% in the treated group (p < 0.001), and the mortality was reduced from 67% to 0% (p < 0.001), that is, to a greater extent than with tedisamil (1.0 mg/kg) alone. The results show that the blockade of Ito by tedisamil allows a reduction of reperfusion-induced mortality and that a specific IK blocker (E-4031) is devoid of antifibrillatory action in the anesthetized rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357778 TI - Effect of propionyl-L-carnitine in a rat model of peripheral arteriopathy: a functional, histologic, and NMR spectroscopic study. AB - Propionyl-L-carnitine (PLC) has been shown to exert beneficial effects in experimental models of peripheral arterial diseases, such as ergotamine-induced tail gangrene and bilateral femoral arteries occlusion in rats. These models, however, present some drawbacks. The present study was performed to determine whether repeated oral administration of PLC improves the functional, histologic, and metabolic parameters in rats with long-lasting chemically induced peripheral arteriopathy. Peripheral arteriopathy was induced by injecting Na laurate in both the femoral arteries of rats. The walking capacity of the animals (treadmill test) was evaluated at different times and up to 5 weeks after Na laurate injection. Histological examination of vessels and muscles was performed at the end of the experimental period (5 weeks). In separate experiments the level of high-energy phosphates was determined with 31P NMR methodology in the leg muscles. Injection of Na laurate impaired (p < 0.05) the walking capacity of rats, caused thickening of the intima and marked narrowing of the vasal lumen, and reduced the ATP and PCr levels in muscles by 42% and 25%, respectively. PLC given orally for 7 days at 30, 60, 120, and 250 mg/kg dose-dependently decreased the severity of walking capacity impairment by 19%, 41%, 64%, and 71%, respectively. Long-term administration (4 weeks) of PLC (60 and 250 mg/kg os) caused a significant improvement of walking capacity throughout the entire period. The improvement persisted 1 week after discontinuation of the treatment. The severity of the vascular and muscular damages was markedly reduced, particularly in animals treated with the highest dose. Alterations in ATP and PCr levels were significantly (p < 0.05) diminished by PLC (120 mg/kg os) administered daily for 15 days starting 24 hours after Na laurate injection, or for 11 days starting 4 days after Na laurate. The dextro-isomer of the compound was completely inactive, and L-carnitine improved motor performance to a much lesser degree than an identical dose of PLC. It is suggested that the activity of PLC is linked to its metabolic effects on fatty acid oxidation, with consequent preservation of high-energy phosphate levels. PMID- 8357779 TI - Effects of cicletanine on the urinary excretion of prostanoids and kallikrein, and on renal function in man. AB - The effects of cicletanine, a new antihypertensive agent, on the prostaglandin kallikrein system and the renin-angiotensin system were studied. A single oral dose of 200 mg cicletanine or placebo was administered to 9 healthy male volunteers, with samples of blood and urine obtained before and 2 hours after drug administration. Cicletanine increased the urine flow, urinary excretion of sodium, and fractional excretion of sodium by 47%, 115%, and 104%, respectively. While the excretion of 6-keto-prostaglandin-F1 alpha was enhanced significantly, urinary excretion of thromboxane-B2, prostaglandin-E2, and kallikrein were unchanged. Cicletanine also did not alter plasma renin activity, plasma aldosterone concentration, or creatinine clearance. These observations suggest that cicletanine may suppress sodium reabsorption at the nephron, and it may stimulate prostacyclin generation with no effect on that of thromboxane-A2. Thus cicletanine may be beneficial in the management of cardiovascular disorders in which the equilibrium between prostacyclin and thromboxane is disturbed. PMID- 8357780 TI - Inhibitory effect of clentiazem (TA-3090), a new calcium antagonist, on balloon catheter-induced intimal thickening of rabbit aorta. AB - Male Japanese white rabbits were fed a restricted amount (100 g/head/day) of an atherogenic diet containing 0.2% cholesterol and 6% peanut oil during an 8-week experimental period. Atherosclerotic lesions, characterized by intimal thickening with lipid deposition, were produced by de-endothelialization of the rabbit aorta with a 4 F balloon catheter halfway through the experiment. Clentiazem (TA-3090), a new calcium antagonist, was administered at an oral dose of 30 mg/kg/day for 4 weeks starting on the day of deendothelialization. Clentiazem significantly depressed the intimal thickening without any effect on serum lipid levels. Clentiazem (1, 3, and 10 microM) significantly and dose-dependently inhibited the in vitro proliferation of smooth muscle cells that had been explanted from the neointima of the deendothelialized aorta. At a higher concentration, this drug markedly inhibited collagen-induced aggregation of rabbit platelets. Diltiazem also showed similar effects, but the effects of clentiazem were more potent than those of diltiazem. These results suggest that clentiazem exhibits an antiatherogenic effect, at least partly through prevention of smooth muscle cell proliferation in atheromatous lesions, in addition to its hypotensive action. PMID- 8357781 TI - Effects of a new calcium antagonist, CD-832, on experimental coronary artery spasm in miniature pigs. AB - The effects of a new calcium antagonist, CD-832, on experimental coronary artery spasms were studied in Gottingen miniature pigs. Pigs underwent endothelial denudation at the left anterior descending coronary artery using a balloon catheter. Changes in the diameter of the denuded and nondenuded site in response to an intracoronary administration of serotonin (10 micrograms/kg) or histamine (10 micrograms/kg) were assessed quantitatively by selective coronary arteriography 1 week after endothelial denudation. Percent reductions of the coronary artery diameter induced by serotonin or histamine in the denuded site were significantly greater than those in the nondenuded site (p < 0.01). Coronary artery spasm induced by serotonin or histamine in the denuded site was attenuated in a dose-dependent manner by intravenous infusion of CD-832 (10 and 30 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min). The degrees of inhibition of coronary artery spasm by CD-832 were similar to those produced by nifedipine. CD-832 and nifedipine at the high dose caused comparable increases in the basal coronary artery diameter. These results suggest that CD-832 may be a useful drug for the treatment of coronary artery spasm. PMID- 8357783 TI - Trends in cardiac medicine: the American Heart Association meeting, New Orleans, November 16-19, 1992. PMID- 8357784 TI - Effects of cytokines, anti-cancer agents and cocarcinogen on DNA synthesis in hair bulb cells. AB - We analysed the effects of cytokines, anti-cancer agents and cocarcinogen on DNA synthesis in human hair germinative cells cultured in serum-free media. Epidermal growth factor and gamma interferon were found to inhibit DNA synthesis slightly, while strong inhibition was demonstrated by doxorubicin, cytosine arabinoside and tetradecanoyl-phorbolacetate. Basic fibroblast growth factor had very little influence on DNA synthesis. This organ culture model in serum-free media is a useful method by which to examine the effects of various cytokines and drugs on DNA synthesis in hair germinative cells and/or to study the pathogenesis of various alopecia diseases. PMID- 8357782 TI - The QUinapril Ischemic Event Trial (QUIET) design and methods: evaluation of chronic ACE inhibitor therapy after coronary artery intervention. AB - The rationale, trial design, and statistical aspects of QUIET, the QUinapril Ischemic Event Trial, are described. QUIET is a prospective, double-blind placebo controlled study that will assess the ability of the angiotensin-converting enzyme (ACE) inhibitor quinapril to reduce the rate of cardiac ischemic events and to slow or prevent the development of coronary artery atherosclerosis as assessed by serial angiography in a normolipidemic population without left ventricular dysfunction. The study began in September 1991 and has completed recruitment with 1740 patients across 38 centers (28 U.S., 4 Canada, 6 Europe) by the end of 1992. Patients are randomized to 20 mg of quinapril or placebo once daily and continue in the study for 3 years. Study completion is projected for 1995. PMID- 8357786 TI - Histocompatibility antigens in Egyptians with cutaneous leishmaniasis: a preliminary study. AB - The frequency of human leucocytic antigens (HLA) were studied in 27 patients with cutaneous leishmaniasis to evaluate the role of HLA antigens as genetic markers in the pathogenesis of this protozoal skin infection. A significant statistical association was observed between HLA-A11, -B5 and -B7 antigens and diffuse cutaneous leishmaniasis. In conclusion, study of immune response genes could be of value to understand the pathogenic mechanisms responsible for cutaneous leishmaniasis. PMID- 8357785 TI - Expression of basement membrane components in skin equivalents--influence of dermal fibroblasts. AB - We have made a skin equivalent constructed of fibroblasts embedded in a type I collagen, with an overlying stratified keratinocyte epithelium to examine formation of the basement membrane. We assessed the influence of the existence and species of fibroblasts in the collagen gel. Cultured human keratinocytes were well attached to the dermal equivalent. Plating efficiency was not clearly different among several types of gel. On the control and mouse fibroblast gel, sheet formation was delayed and epithelial stratification on the human fibroblast gel was more remarkable than on the control gel. On the human fibroblast gel, we observed the expression of basement membrane components (bulbous phemphigoid antigen, laminin, type IV collagen and fibronectin) between the sheet of cultured keratinocytes and the human fibroblast gel earlier than those on the control gel and mouse fibroblast gel. Type VIII collagen was not observed in any of the models at 4 weeks. PMID- 8357787 TI - Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline. AB - The existence of a defect in the skin barrier of patients with atopic dermatitis (AD) was demonstrated and its importance in the pathogenesis of AD was emphasized. In order to evaluate the penetration properties of the stratum corneum of AD patients, the in vivo skin response to the penetration of dimethyl sulfoxide (DMSO) and in vitro response to the penetration of theophylline utilizing a diffusion chamber were studied. Both methods demonstrated an increasing level of penetration through the epidermal stratum corneum, with greatest penetration being evident with lesional skin, followed by AD non lesional and then the normal control. However, statistical significances existed only between non-lesional and lesional skins in the case of the DMSO test, and between the normal control and non-lesional skin in the case of the diffusion chamber analysis using theophylline. Increased penetration of a non-specific nature is important in the pathogenesis of AD. PMID- 8357788 TI - Labeling of fractured human skin with antibodies to BM 600/nicein, epiligrin, kalinin and other matrix components. AB - A variety of methods were used to fracture the dermal-epidermal junction (DEJ) of human skin. These included warm and hot phosphate buffered saline, trypsin, cold 1 M salt, potassium bromide and proteolytic digestion with dispase. The localization and sensitivity of basement membrane components (bullous pemphigoid antigen, BM 600/nicein, epiligrin, kalinin, laminin, collagens IV and VII (EBA antigen) and linkin) were determined after the DEJ was fractured by each method. We found that the basement membrane zone proteins, BM 600/nicein, epiligrin and kalinin remained with the dermal side of the DEJ fractured through the lamina lucida by cold salt, phosphate buffered saline and potassium bromide. BM 600/nicein, epiligrin and kalinin were not detected after treatment with trypsin. In contrast, laminin, another glycoprotein in the lamina lucida, was insensitive to all of the procedures, but co-localized to the dermal side of DEJ-fractured skin. We also found that separation of the DEJ with brief exposure of skin to 56 degrees C provided a useful substrate for testing the autoantibodies in the sera of patients with epidermolysis bullosa acquisita (EBA). Heat-separated skin can be prepared in a significantly shorter period of time than salt-separated skin. PMID- 8357789 TI - Transmission of conformational change from the heparin binding site to the reactive center of antithrombin. AB - Heparin greatly increases the rates at which antithrombin inhibits target proteinases. An important part of this rate acceleration is a heparin-induced conformational change in antithrombin. To answer the question of whether or not this change is transmitted to the reactive center, we have prepared a recombinant P1 mutant of antithrombin, R393C, labeled the cysteine with nitrobenzofuran (NBD) fluorophore, and examined the perturbation of NBD fluorescence intensity as a function of bound sulfated oligosaccharide. Two high-affinity heparins, low affinity heparin, and dextran sulfate were used. We found (i) that binding to antithrombin of all these oligosaccharides resulted in transmission of conformational change to P1 in the reactive center, (ii) that these oligosaccharides all gave enhancements of the rate of inhibition of factor Xa beyond any contribution from surface approximation, and (iii) that the degree of perturbation of P1 correlated with the enhancement of the rate of factor Xa inhibition that was not due to surface approximation. PMID- 8357790 TI - Atomic force microscope measurements of nucleosome cores assembled along defined DNA sequences. AB - We have found that the atomic force microscope (AFM) can be used to image the "beads-on-a-string" chromatin structure in a normal air environment following adsorption onto a cover glass substrate. Individual nucleosome cores and linker DNA could be resolved clearly along chromatin fibers that were reconstituted using histone octamers and a tandemly repeated 208-bp nucleosome positioning DNA sequence (208-18). AFM measurements showed that the compaction of the 3780-bp DNA by different loadings of histone octamers was consistent with 146 bp of DNA wrapped 1.75 turns about the histone octamer to form the 11-nm nucleosome core. Precise internucleosome core spacing measurements could be performed along the chromatin fiber axis. In other experiments, AFM images of chromatin reconstituted using closed circular DNA showed highly tangled beaded fibers, as expected. These images and measurements demonstrate that AFM can provide useful high-resolution structural information about chromatin that can be used to complement other more established techniques such as electron microscopy. PMID- 8357791 TI - Nuclear matrix association of multiple sequence-specific DNA binding activities related to SP-1, ATF, CCAAT, C/EBP, OCT-1, and AP-1. AB - The association of DNA binding proteins with the nuclear matrix may be related to a functional role of this subcellular structure in chromatin organization and gene regulation. In this study, nuclear matrix preparations from human HeLa S3 cervical carcinoma and rat ROS 17/2.8 osteosarcoma cells were assayed for the presence of DNA binding activities using consensus binding sequences of well characterized transcription factors as probes. Competition analysis shows that each probe interacts with different nuclear matrix proteins in a sequence specific manner and that DNA binding activities related to or identical with SP 1, ATF, CCAAT, C/EBP, OCT-1, and AP-1 are present in the nuclear matrix fraction of different cell types. Comparison of the relative abundance of these transcription factor binding activities in nuclear matrix and nonmatrix nuclear fractions suggests that the distribution between these two fractions is cell type specific, cell growth dependent, or independent of these biological parameters. These results are consistent with the postulated role of the nuclear matrix in transcriptional regulation of gene expression. PMID- 8357792 TI - Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras. AB - The three-dimensional structures and biochemical properties of two mutants of the G-domain (residues 1-166) of p21H-ras, p21 (G12D) and p21 (G12P), have been determined in the triphosphate-bound form using guanosine 5'-(beta,gamma imido)triphosphate (GppNHp). They correspond to the most frequent oncogenic and the only nononcogenic mutation of Gly-12, respectively. The G12D mutation is the only mutant analyzed so far that crystallizes in a space group different from wild type, and the atomic model of the protein shows the most drastic changes of structure around the active site as compared to wild-type p21. This is due to the interactions of the aspartic acid side chain with Tyr-32, Gln-61, and the gamma phosphate, which result in reduced mobility of these structural elements. The interaction between the carboxylate group of Asp-12 and the gamma-phosphate is mediated by a shared proton, which we show by 31P NMR measurements to exist in solution as well. The structure of p21 (G12P) is remarkably similar to that of wild-type p21 in the active site, including the position of the nucleophilic water. The pyrrolidine ring of Pro-12 points outward and seems to be responsible for the weaker affinity toward GAP (GTPase-activating protein) and the failure of GAP to stimulate GTP hydrolysis. PMID- 8357793 TI - Heteronuclear nuclear magnetic resonance studies of cobalt corrinoids. 15. The structure of glutathionylcobalamin: a 1H and 13C two-dimensional nuclear magnetic resonance study at 600 MHz. AB - Glutathionylcobalamin (GSCbl), the complex formed between glutathione (GSH, gamma glutamylcysteinylglycine) and aquacobalamin (H2OCbl), has been implicated as an intermediate in the pathway for the formation of the cobalamin coenzymes. In chemical model studies, GSCbl has been shown to be a substrate for methylcobalamin formation in the presence of S-adenosylmethionine and a thiol reductant. Although GSCbl was first described in 1964, the structure of this compound, particularly the site of GSH coordination, has been unknown. GSCbl was prepared by reacting GSH (5-fold molar excess) with H2OCbl in 0.1 M sodium phosphate (pH 6.5) and was purified by gel-permeation chromatography on a Bio-Gel P2 polyacrylamide column. By use of a combination of homonuclear [homonuclear J correlated spectroscopy (COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA), and absorption-mode nuclear Overhauser effect spectroscopy (NOESY)] and inverse detected heteronuclear [1H-detected heteronuclear multiple-quantum coherence (HMQC) and 1H-detected multiple-bond heteronuclear multiple-quantum coherence (HMBC) spectroscopies] two-dimensional NMR methods at 600 MHz, the complete 1H and 13C NMR spectra of GSCbl have now been assigned. Comparison of the 1H and 13C NMR chemical shifts of the GS moiety of GSCbl to those of free GSH and GS- shows that by far the largest differences occur at the cysteine alpha and beta positions. This result strongly suggests that GSH is coordinated to the cobalt atom in GSCbl via the cysteine sulfur atom. PMID- 8357794 TI - The solution structures of mutant calbindin D9k's, as determined by NMR, show that the calcium-binding site can adopt different folds. AB - The complete 1H NMR assignments have been obtained for five mutant proteins of calbindin D9k and the three-dimensional solution structures determined for two of the mutants. The structures have been determined using distance geometry and simulated annealing, with distance constraints from NMR. All mutants have modifications in the first calcium-binding site of calbindin (the N-terminal site designated the pseudo-EF-hand). The 3D structure of the mutant with the most extensive modifications in the pseudo-EF-hand shows that the site has turned inside-out and coordinates calcium as in the normal EF-hand (the C-terminal site). In a pseudo-EF-hand loop the calcium is coordinated by main-chain carbonyls, whereas calcium in the normal EF-hand is coordinated by side-chain carboxylates. The 3D structures and 1H NMR assignments show that in order to accomplish a change in the coordinating ligands of the pseudo-EF-hand the loop must be 12 residues long and have glycine in the sixth position. It does, however, seem possible to have alanine instead of aspartic acid in the first calcium coordinating position. The overall global fold of the proteins has not been affected by the mutations in the calcium-binding site, as compared to the wild-type calbindin D9k [Kordel, J., Skelton, N. J., Akke, M., & Chazin, W. J. (1993) J. Mol. Biol. (in press)]. The structures consist of two helix-calcium binding loop-helix motifs, the so called EF-hands, and the loops are connected by a short antiparallel beta-sheet. All helices are pairwise in an antiparallel orientation. PMID- 8357795 TI - Crystal structure of a fluorescent derivative of RNase A. AB - The crystal structure of RNase A chemically modified with the fluorescent probe, N-[[(iodoacetyl)-amino]ethyl]-5-naphthylamine-1-sulfonic acid (1,5-IAENS), has been solved and refined to high resolution. It yields information on the mode of binding, the mobility of a probe commonly used in spectroscopic studies, and anion binding sites in RNase A. Trigonal crystals of the fluorescent derivative grown in sodium or cesium chloride and ammonium sulfate, pH 5.1, were nearly isomorphous with those of a semisynthetic RNase [DeMel, et al. (1992) J. Biol. Chem. 267, 247-256]. Refinement starting from semisynthetic RNase led to a model with R = 20% against 1.7-A diffraction data from crystals in ammonium sulfate and another model with R = 17% against 1.9-A data taken in the presence of 3 M NaCl. The second model contains three chloride ions: one is at the active site, and the other two are at molecular interfaces. Otherwise, the two models are very similar. The fluorophore has very little effect on the protein conformation. It is found to be covalently attached to the active site His-12 with the naphthyl group stacked on the imidazole ring of His-119. It remains largely accessible to solvent and in a polar environment on the protein surface, even though the fluorescence emission spectrum is blue shifted as it is in nonpolar solvents. PMID- 8357796 TI - X-ray crystallographic determination of the structure of bovine lens leucine aminopeptidase complexed with amastatin: formulation of a catalytic mechanism featuring a gem-diolate transition state. AB - The structure of the complex of bovine lens leucine aminopeptidase (blLAP) with the slow-, tight-binding inhibitor amastatin has been determined by X-ray crystallography. X-ray diffraction data were collected at -150 degrees C from a single blLAP-amastatin crystal which under the data collection conditions was of the space group P6(3)22 with unit cell parameters a = 130.3 A and c = 121.9 A. The structure of the blLAP-amastatin complex was determined by molecular replacement, using the structure of native blLAP as the starting model. Refinement of the blLAP-amastatin model plus 132 water molecules against data from 10.0- to 2.4-A resolution resulted in a final structure with a crystallographic residual of 0.198. The binding mode of amastatin is similar to that of bestatin, the structure of whose complex with blLAP has previously been determined. Of particular note, the N-terminus-to-C-terminus orientation of the two bound inhibitors is the same. The two N-terminal residues of amastatin and bestatin occupy the same binding sites, which are most likely S1 and S'1. The slow binding of amastatin and bestatin may be partially attributable to a binding mechanism in which the two active site metals are sequentially coordinated by the P1 amino and hydroxyl groups of these inhibitors. A catalytic mechanism for blLAP is proposed based on the binding modes of amastatin and bestatin and plausible binding modes of a dipeptide substrate and its putative gem-diolate transition state which were modeled into the active site of blLAP after the binding mode of amastatin. The proposed catalytic mechanism invokes roles for the catalytic metals in binding and activating the substrate and in stabilizing the transition state. The mechanism also includes roles for Asp-255 as a general base, Arg-336 as an additional electrophilic substrate activator and transition state stabilizer, and Lys-262 as a proton shuttle. PMID- 8357797 TI - Role of conformational change in the fumarase reaction cycle. AB - Activation of fumarase by high concentrations of either malate or fumarate, often referred to as negative cooperativity, can be explained without assuming additional sites of substrate action or subunit-subunit interactions. The following observations support a model based on a rate-dependent recycling of free enzyme through a sequence of conformational states that differ in substrate specificity and catalytic activity: (1) Displacement from equilibrium of a radiolabeled malate/fumarate probe is readily induced by moderate concentrations of either substrate. This phenomenon, called substrate-induced countertransport, indicates that the steady-state ratio of free enzyme forms is very dependent on substrate concentration. (2) Related to this, the back-labeling that can be observed with either 14C product with either substrate in the steady state is more rapid than expected for a single free enzyme state model. (3) Fumarate, more strongly than malate, shows competitive effects as a product. This may reflect a higher affinity of fumarate for an isoform that also reacts with malate. (4) P(i), an activator of fumarase at midrange substrate concentration, overcomes strong competitive inhibition by fumarate of the M-->F reaction and increases recycling as shown by its effect on counterflow. To the extent that these effects are due to buffer activation, they suggest that proton transfer between solvent and the enzyme site is important in determining the recycling rate. (5) Transaconitate, a competitive inhibitor, overcomes counterflow induced by either substrate, indicating that recycling events occur in the enzyme-transaconitate complex. PMID- 8357798 TI - Low-density lipoprotein modification and arterial wall accumulation in a rabbit model of atherosclerosis. AB - Chemically or enzymatically modified low-density lipoproteins (LDL), with and without changes in surface charge, were studied in vivo in the healing, balloon catheter-deendothelialized rabbit aorta to determine the effect of LDL modification on its accumulation in arterial lesions. In this model, in which healing (reendothelialization) proceeds radially outward from individual aortic branch arteries, it was previously shown by autoradiography that two kinetically distinct compartments accumulated 125I-labeled LDL. In aortic regions which were still deendothelialized, accumulation was diffuse and labile. In contrast, at the edges of the islands of regenerating endothelium, LDL accumulation was intensely focal, as it is in human atherosclerotic lesions, and persisted for at least 40 h after injection in spite of falling levels of radiolabeled LDL in plasma [Chang, M. Y., et al. (1992) Arterioscler. Thromb. 12, 1088-1098]. In the present study, modified LDLs with gradations in charge change were prepared to clarify the role of changes in surface charge on focal aortic LDL accumulation. Oxidized LDL (weakly anionized), desialated LDL (weakly cationized), and reductively methylated LDL (no change in net charge) all accumulated focally. Focal accumulation of native LDL also occurred in ballooned rabbits fed probucol to inhibit LDL oxidation. Strongly anionized succinylated and diazobenzenearsonylated LDL and strongly cationized dimethylpropanediamine LDL did not accumulate focally. The results support the concept that focal sequestration of LDL in arterial lesions is mediated by specific, oxidation independent patterns of charge and polarity on LDL which are disrupted by major changes in LDL surface charge. PMID- 8357799 TI - Primary structure of and studies on Acanthamoeba actophorin. AB - We determined the amino acid sequence of the actin monomer binding/actin filament severing protein actophorin from Acanthamoeba castellanii by automated Edman degradation of peptide fragments and by sequencing of full-length cDNA. Actophorin consists of 138 amino acids (calculated molecular weight of 15,543) and shares a high degree of sequence similarity to other low molecular weight actin monomer sequestering proteins, especially vertebrate cofilin, vertebrate actin depolymerizing factor/destrin, and echinoderm depactin. Actophorin is smaller and does not contain a nuclear localization sequence like the related vertebrate proteins. Southern blot analysis indicates that actophorin is a single copy gene; however, Northern blots show two distinct mRNA species of 1 and 0.9 kb in size. Homogeneous recombinant actophorin purified from Escherichia coli is indistinguishable from the native protein in its physical properties and in biochemical assays of its interaction with actin, but is less reactive with three monoclonal antibodies raised against the native protein. The NH2 terminus of native actophrin is blocked, while the initiating methionine residue is removed from recombinant actophorin. This difference has no measurable effect on activity. By fluorescent antibody staining of Acanthamoeba, actophorin colocalizes with actin filaments in the cortical cytoplasm, especially at the leading edge of the cell. Additionally, actophorin binds phosphatidylinositol 4',5'-bisphosphate. The recombinant actophorin forms X-ray diffraction quality crystals of superior quality in poly(ethylene glycol)/2-propanol and, like the native crystal form, belongs to space group P2(1)2(1)2(1). PMID- 8357800 TI - Three-dimensional model for the membrane domain of Escherichia coli leader peptidase based on disulfide mapping. AB - We have mapped the interface between the two transmembrane alpha-helices in the membrane domain of the Escherichia coli enzyme leader peptidase by analyzing disulfides formed between pairs of cysteine residues introduced near their respective periplasmic ends. The interface is formed primarily from aliphatic amino acids, and the two helices appear to pack against each other in a left handed supercoil. We suggest that disulfide mapping may be a generally applicable approach for the construction of models of helix-helix interfaces in membrane proteins. PMID- 8357801 TI - The substrates of a sodium- and chloride-coupled gamma-aminobutyric acid transporter protect multiple sites throughout the protein against proteolytic cleavage. AB - Fragments of the (Na(+) + Cl-)-coupled GABAA transporter were produced by proteolysis of membrane vesicles and reconstituted preparations from rat brain. The former were digested with Pronase, the latter with trypsin. Fragments with different apparent molecular masses were recognized by sequence-directed antibodies raised against this transporter. When GABA was present in the digestion medium, the generation of these fragments was almost entirely blocked. At the same time, the neurotransmitter largely prevented the loss of activity caused by the protease. The effect was specific for GABA; protection was not afforded by other neurotransmitters. It was only observed when the two cosubstrates, sodium and chloride, were present on the same side of the membrane as GABA. The results indicate that the transporter may exist in two conformations. In the absence of one or more of the substrates, multiple sites located throughout the transporter are accessible to the proteases. In the presence of all three substrates--conditions favoring the formation of the translocation complex--the conformation is changed such that these sites become inaccessible to protease action. PMID- 8357802 TI - Minimum intron requirements for tRNA splicing and nuclear transport in Xenopus oocytes. AB - The presence or absence of an intron defines two classes of eukaryotic nuclear tRNA genes whose transcripts differ in a requirement for splicing. Using quantitative nuclear microinjection, we have previously found that nucleocytoplasmic transport of these two classes of tRNAs involves pathways which differ in one or more limiting components. To examine substrate features which distinguish these two pathways, a series of variants of a Xenopus tRNA(Tyr) gene were constructed in which the intron size was altered. The splicing and transport properties of the resulting transcripts were examined in oocyte microinjection and in vitro processing assays. The addition of one or two nucleotides at the splice site equivalent in an intronless gene produced transcripts which could be transported without splicing. However, transport was reduced relative to the mature-sequence tRNA, suggesting the anticodon loop (interrupted in pre-tRNAs) may be recognized by the intronless tRNA transport apparatus. Transcripts with four- or six-nucleotide intervening sequences were incompletely spliced with cleavage at only the 3' splice site. Neither unspliced precursor nor partially processed intermediates were efficiently transported. The results of coinjection experiments using tRNA and pre-tRNA competitors suggest that simple retention by the splicing apparatus may not account for failure to export these RNAs. Finally, a requirement for splicing is not unique to transport of pre-tRNA(Tyr) since a pre-tRNA(3Leu) variant which was not spliced was also not exported. PMID- 8357803 TI - Photoaffinity labeling of the vesamicol receptor of cholinergic synaptic vesicles. AB - On the basis of the high-affinity vesamicol analog 4-aminobenzovesamicol (ABV), a tritiated, arylazido ligand (azidoABV) of the vesamicol receptor (VR) in cholinergic synaptic vesicles was synthesized. azidoABV is an inhibitor of acetylcholine (AcCh) active transport, and it binds to the VR with higher affinity than vesamicol. The rate of dissociation of azidoABV from synaptic vesicles is 0.058 +/- 0.003 min-1 at 20 degrees C (about 3-fold slower than that of vesamicol), and the equilibrium dissociation constant is 2 nM (about 4-fold lower than that of vesamicol). Photolysis of [3H]azidoABV in the presence of a stoichiometric excess of the VR led to incorporation of 28% of the radiolabel, of which 57% was blocked by 50 microM vesamicol. Sodium dodecyl sulfate polyacrylamide gel electrophoretic analysis of the labeled vesicles revealed, after autofluorography, specific labeling over a broad molecular weight range that extended from about 50 to 200 kDa. This labeling pattern was essentially the same as that obtained with an azido analog of AcCh that was used to label the AcCh transporter (Rogers, G.A., & Parsons, S. M. (1992) Biochemistry 31, 5770 5777). In addition, about 6% of the radioligand that was specifically incorporated into proteins with M(r) greater than 12 kDa labeled four polypeptides that corresponded to bands in the Coomassie image at M(r) = 23, 33, 35, and 38 kDa. The results suggest that the VR exists as part of a complex system of subunits. PMID- 8357804 TI - A high-affinity site for acetylcholine occurs close to the alpha-gamma subunit interface of Torpedo nicotinic acetylcholine receptor. AB - Affinity labeling techniques have been used to investigate the location of high affinity binding sites for cholinergic agonists on the Torpedo acetylcholine receptor and the extent of overlap of these sites with those for long alpha neurotoxins. Following reduction of the receptor by dithiothreitol, reaction with [3H]bromoacetylcholine leads to covalent incorporation into each of the two alpha subunits. At high concentrations of [3H]bromoacetylcholine (240 microM) and with prolonged incubation times (1-2 h), this labeling was not inhibited by either alpha-bungarotoxin or alpha-najatoxin. Following maximum labeling by [3H]bromoacetylcholine, no residual high binding sites for [125I]-alpha bungarotoxin could be detected in the membrane-bound receptor, but 50% of the original sites were recovered by receptor solubilization. Since it has previously been reported that one of the two sites for alpha-bungarotoxin in the membrane bound receptor is readily reversible but is converted to a high-affinity state by solubilization [Conti-Tronconi, B. M., Tang, F., Walgrave, S., & Gallagher, W. (1990) Biochemistry 29, 1046-1054], these results demonstrate that the covalently bound agonist inhibits the binding of alpha-bungarotoxin only to its higher affinity site in the membrane. When [3H]bromoacetylcholine labeling was carried out after reduction of the receptor by sodium borohydride rather than dithiothreitol, both alpha and gamma subunits of the receptor were labeled. Labeling of both subunits was completely inhibited if the receptor was first reduced with dithiothreitol and the alpha subunit sites were previously covalently labeled by unlabeled bromoacetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357805 TI - Mechanism of fluorescent fatty acid transfer from adipocyte fatty acid binding protein to membranes. AB - Adipocyte fatty acid binding protein (A-FABP) is a 15-kDa protein found in high abundance in the cytosol of adipose cells. To better understand the role of this protein in intracellular free fatty acid (ffa) transport, the mechanism of ffa transfer from A-FABP to model membranes was examined by monitoring the transfer of fluorescent anthroyloxy ffa (AOffa) to small unilamellar phospholipid vesicles, using a resonance energy transfer assay. Structural features of ffa that increase aqueous solubility, such as shorter chain length and unsaturation, did not increase the AOffa transfer rate. In addition, solution conditions that increase the aqueous solubility of ffa, such as decreasing ionic strength and increasing pH, had little effect on AOffa transfer from A-FABP to membranes. These results suggest that AOffa do not transfer through the aqueous phase. The small entropic contribution to the free energy of the transfer process provides further evidence that AOffa may not travel through the surrounding aqueous environment when transferred from A-FABP to phospholipid membranes. Finally, the rate of AOffa transfer from A-FABP was directly dependent on the concentration of the acceptor membranes. These studies suggest that AOffa transfer from A-FABP to phospholipid vesicles may occur via transient collisional interactions between the protein and membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357806 TI - G protein beta gamma subunit: physical and chemical characterization. AB - The beta gamma subunits of heterotrimeric G proteins play a central role in regulating the function of the G protein alpha subunits and in modulating the activity of several enzymes and ion channels. We have used the signature tryptic cleavage pattern of native beta gamma from bovine brain as a starting point for our analysis of its physical and chemical properties. Digestion of bovine brain beta gamma with trypsin yields only 2 beta-derived fragments, with relative mobilities on SDS-PAGE of 14 kDa (amino terminal) and 27 kDa (carboxyl terminal), despite the presence of 32 potential tryptic cleavage sites in the beta 1 subunit. Trypsin-cleaved beta gamma remains in a complex that has the same apparent sedimentation coefficient as intact beta gamma, and retains its ability to associate functionally with the alpha o subunit. Comparison of the incorporation of [14C]iodoacetamide into reduced denatured beta and unreduced denatured beta showed that there are no disulfide bonds in the molecule to hold the complex together. The brain beta and gamma subunits can be cross-linked by 1,6-bis(maleimido)hexane to form a 46-kDa product on SDS-PAGE, and trypsin cleavage of cross-linked beta gamma shows that gamma is cross-linked to the 14 kDa amino-terminal fragment of the beta subunit. On the basis of its primary sequence, the beta subunit is predicted to form a repetitive structure encompassing the 27-kDa fragment and part of the 14-kDa fragment. Analysis of the thermal denaturation of trypsin-cleaved beta gamma supports this prediction and confirms that both fragments retain stable tertiary structures following tryptic cleavage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357807 TI - The class I major histocompatibility complex related Fc receptor shows pH dependent stability differences correlating with immunoglobulin binding and release. AB - Maternal immunoglobulin G (IgG) in milk is transported to the bloodstream of newborn rodents via an Fc receptor (FcRn) expressed in the gut. The receptor shows a striking structural similarity to class I major histocompatibility complex (MHC) molecules, being composed of a related heavy chain and the identical light chain (beta 2-microglobulin). FcRn binds IgG at the pH of milk in the proximal intestine (pH 6.0-6.5) and releases it at the pH of blood (pH approximately 7.5). We have compared the stability of a soluble form of FcRn in these two pH ranges and find that the heterodimer is markedly more stable at the permissive pH for IgG binding. Using the rate of beta 2m exchange as a correlate of heterodimer stability, we find that exchange is more than 10 times slower at pH 6.1 compared to pH 7.8. Thermal denaturation profiles of FcRn heterodimers at pH 8.0 indicate a two-step, sequential heavy-chain (Tm = 52 degrees C) and beta 2m (Tm = 67 degrees C) denaturation. By contrast, at pH 6.0, a single transition is observed, centered at 62 degrees C, corresponding to denaturation of both chains. The striking difference in stability does not appear to be correlated with the binding of peptide as in class I MHC molecules, because analysis of purified FcRn by acid dissociation and sequencing suggests that FcRn is not associated with cellular peptides. These results are indicative of pH-dependent conformational changes in the FcRn heterodimer, which may be related to its physiological function. PMID- 8357808 TI - Alcohol-induced protein folding transitions in platelet factor 4: the O-state. AB - Platelet factor 4 (PF4) (7800 daltons) is an anti-parallel beta-sheet, alpha/beta class protein whose tertiary structure is stabilized by the presence of two disulfide bonds. Titration of PF4 with 2-propanol or similar low molecular weight, aliphatic alcohols induces reversible protein folding transitions which are observed to be in slow exchange on the 600-MHz 1H NMR time scale. Line fitting of resolved resonances assigned to ring protons of Y60, H35, H23, and alpha H of K50 in native and alcohol-induced states (O-states) allows derivation of folding equilibrium constants and exchange kinetics. Folding exchange rates vary between 5 and 100 s-1 on going from 9.8 to 3.3 M2-propanol. Simple linear extrapolation to 0 M2-propanol yields an O-state to N-state exchange rate of about 500 s-1, i.e., millisecond time scale. At relatively high 2-propanol concentration (>9.5 M), where the O-state is predominant (>90%), NMR spectra suggest a more "unfolded" structure, while CD data indicate the preservation of considerable secondary structure. Increasing 2-propanol from 3.3 to 9.8 M, however, shifts the CD-derived fractional compositions significantly, with overall beta-structure decreasing by about 20% and alpha-helix composition increasing by about 25%. Alcohol-jump experiments, which identify O-state long lived NHs in the NMR spectrum of native PF4, indicate folding transition reversibility and conservation of about 15 long-lived NHs in native and O-states. Most of these NHs are assigned to residues in anti-parallel beta-sheet structure. Of these 15 NHs, H/D exchange rates, although variably reduced in the O-state, are generally still long-lived compared with random coil H/D exchange. Overall, the PF4 O-state is a stable intermediate with an apparently more highly fluctuating anti-parallel beta-sheet structure and a more stabilized C-terminal alpha-helix. PMID- 8357809 TI - Structural effects of the C2-methylhypoxanthine:cytosine base pair in B-DNA: A combined NMR and X-ray diffraction study of d(CGC[m2I]AATTCGCG). AB - C2-Methylhypoxanthine (m2I) is a synthetic analog of guanine with the N2-amino group replaced by a methyl group. We have studied the structural consequence of the m2I incorporation in DNA by a combination of X-ray crystallographic, NMR, and enzymatic analyses. The crystal structure of d(CGC[m2I]AATTCGCG) has been solved and refined to an R factor of 20.7% at 2.25-A resolution. In the DNA duplex, the two independent m2I:C base pairs maintain the Watson-Crick scheme. While the C2 methyl group of m2I is in van der Waals contact with the O2 of the base-paired cytosine, it only causes the base pair to have slightly higher propeller twist and buckle angles. Its solution structure was analyzed by the NMR refinement procedure SPEDREF [Robinson, H., & Wang, A. H.-J. (1992) Biochemistry 31, 3524 3533] using 2D nuclear Overhauser effect data. Two starting models, a relaxed fiber model and an X-ray model, were subjected to the NOE-constrained refinement using 1518 NOE cross-peak integrals to arrive at the final models with (NOE) R factors of 13.8% and 14.3%, respectively. The RMSD between the two refined models (all atoms included) is 1.23 A, which presently seems to be near the limit of convergence of NOE-based refinement. The local structures of the two models are in better agreement as measured by the RMSD of the dinucleotide steps, falling in the range 0.54-0.98 A. Both refined solution structures confirm that the m2I dodecamer structure is of the B-DNA type with a narrow minor groove at the AT region, as observed in the crystal. However, significant differences exist between the crystal and solution structures in parameters such as pseudorotation angles, propeller twist angles, etc. The solution structure tends to have a more uniform backbone conformation, an observation consistent with that concluded from the laser Raman study of d(CGCAAATTTGCG) [Benevides, J. M., Wang, A. H.-J., van der Marel, G. A., van Boom, J. H., & Thomas, G. J., J. (1988) Biochemistry 27, 931-938]. Three related dodecamers, d(CGCGAATTCGCG), d(CGC[m2I]AATTCGCG), and d(CGC[e6G]AATTCGCG), were tested as substrates for the restriction endonuclease EcoRI. The m2I dodecamer was active, but the e6G dodecamer was not. Our results illustrate the complementarity in terms of the structural information provided by the two methods, X-ray diffraction and NMR. PMID- 8357810 TI - Strand orientation in the DNA quadruplex formed from the Oxytricha telomere repeat oligonucleotide d(G4T4G4) in solution. AB - The structure formed from the DNA oligonucleotide d(G4T4G4) (Oxy-1.5), which contains the Oxytricha telomere repeat T4G4, has been investigated by two dimensional 1H and 31P NMR spectroscopy. Sequence-specific assignments have been obtained for the 1H and 31P resonances, using a combination of methods including comparisons to the inosine- and uracil-containing derivatives d(G4T4G3I) and d(G4UT3G4). The oligonucleotide forms a symmetrical bimolecular G-quadruplex with four G-quartets and thymine loops at opposite ends of the G-quartets. Guanines are alternatively syn and anti along each "strand" and all of the thymines are anti. The thymines loop diagonally across the G-quartet, resulting in a structure in which adjacent strands are alternately parallel and antiparallel and the glycosidic torsion angles are syn-syn-anti-anti around each G-quartet. There are three different types of grooves, a wide, a narrow, and two medium grooves. A diagonally looped quadruplex is formed in the presence of both Na+ and K+ counterions. The model structure of Oxy-1.5 is compared to the recently published crystal structure of Oxy-1.5 (Kang et al., 1992), which contains many of the same features as those found in solution but differs in that the thymines loop across an edge of the G-quartet. PMID- 8357811 TI - Modulation of the stability of a Lac repressor mediated looped complex by temperature and ions: allosteric regulation by chloride. AB - The lactose repressor of Escherichia coli (LacI) associates to a bidentate tetramer in solution and can simultaneously bind two operators to form a protein mediated "looped complex". Studies have been conducted of the binding of LacI to two operators separated by approximately 11 helical turns of DNA. Quantitative DNase I footprint titration analysis of the stability of the LacI-mediated looped complex reveals that the Gibbs free energy of cyclization (delta Gzeroj) of the looped complex of 11.7 +/- 0.4 kcal/mol is invariant with temperature. van't Hoff analysis reveals a large and positive enthalpy of cyclization (delta H degrees = 12.3 +/- 2.4 kcal/mol) and an entropy that is small and positive (delta S degrees = 2.2 cal/deg). Quantitative DNase I footprint titration and kinetic dissociation studies were also conducted as a function of counter-ion type and concentration. Increasing concentrations of KCl or potassium glutamate destabilize the looped complex, a result completely accounted for by increases in the intrinsic DNA binding free energies. While the value of delta Gzeroj is invariant with ion concentration, chloride is a positive regulator. The value of delta Gzeroj decreases by 1.5 kcal/mol upon substitution of chloride for glutamate. Measurements of delta Gzeroj conducted as a function of chloride concentration at constant ionic strength reveal that approximately one chloride ion per tetramer is bound upon looped complex formation. These results demonstrate specific allosteric regulation of the formation of the LacI-mediated looped complex by a mechanism distinct from the regulation of the constituent protein--DNA interactions. PMID- 8357812 TI - Conformational properties of DNA hairpins with TTT and TTTT loops. AB - The DNA hairpins d[CGATCG-Tn-CGATCG] (n = 3, 4) have been studied by NMR in order to gain information on hairpin conformation and flexibility. Resonance assignments were made using a combination of DQF-COSY, DQF-COSY[31P], NOESY, and 1H-31P-COSY. These data also provide approximate coupling constant information which points out exceptionally flexible regions of the phosphate backbone. The data for both hairpins reveal substantial flexibility within the loop segments. For n = 4, NOESY data alone are insufficient to distinguish between two loop folding motifs, although coupling constant data favor a conformation in which Tb is folded toward the minor groove and is highly exposed to solvent. This is in agreement with chemical shift data and susceptibility to modification by KMnO4. The phosphate backbone between Tc and Td is exceptionally flexible, undergoing a facile exchange between (beta t,gamma+) and (beta+,gamma t) conformers. A similar flexible phosphate is observed between Tc and C7 when n = 3. Differences in stem conformation and dynamics in both hairpins are restricted to the two base pairs adjacent to the stem-loop junction. The C7pG8 stem phosphate appears to flip easily between (zeta-,alpha-) and (zeta-,alpha t) conformers when n = 4 but not when n = 3. Hairpin loop size thus affects the conformational flexibility of the adjacent stem segment. PMID- 8357813 TI - Correlation of DNA sequence specificity of anthramycin and tomaymycin with reaction kinetics and bending of DNA. AB - Anthramycin and tomaymycin are potent antitumor antibiotics belonging to the pyrrolo[1,4]-benzodiazepine [P[1,4]B] group. Their potent biological effects are thought to be due to their ability to react with DNA within the minor groove, forming covalent adducts through the N2 of guanine with the drug molecules overlapping with a 3-4 bp region. In spite of their small molecular weights, the P[1,4]B's show a surprising degree of sequence selectivity, with 5'-PuGPu sequences being the most reactive and 5'-PyGPy sequences being the least reactive [Hertzberg, R. P., Hecht, S. M., Reynolds, V. L., Molineux, I. J., & Hurley, L. H. (1986) Biochemistry 25, 1249-1258]. It has been proposed that inherent DNA flexibility may be one important component of the sequence recognition process for P[1,4]B bonding to DNA, and in this regard, molecular modeling studies are reflective of the experimentally determined hierarchy of bonding sequences [Zakrzewska, K., & Pullman, B. (1986) Biomol. Struct. Dyn. 4, 127-136]. In this study, we have used chemical and enzymatic probes (hydroxyl radical, DNase I) to evaluate drug- and sequence-dependent changes in DNA-adduct conformation, gel electrophoresis to measure drug-induced bending in DNA, and HPLC to measure the reaction kinetics of anthramycin bonding to different sequences. The results show that tomaymycin bonding to DNA induces greater conformational changes in the DNA (i.e., bending and associated narrowing of the minor groove) than anthramycin. In addition, we find that within each drug species (i.e., tomaymycin or anthramycin), sequence specificity correlates with the degree of bending and reaction kinetics such that those sequences with the highest sequence selectivity produce more bending of DNA and react faster with DNA and vice versa. On the basis of these results, we propose that sequence-dependent conformational flexibility may be an important factor in determining the hierarchy of bonding sequences for the P[1,4]B's. PMID- 8357814 TI - Fura-2 transport in toad urinary bladder epithelium: effects of antidiuretic hormone, colchicine and osmotic gradients. AB - Fluorescence is transferred across the toad urinary bladder when fura-2/AM is added to the mucosal or serosal sides of the epithelium. It was now observed that: (1) Oxytocin (20 nM, serosal) increased fluorescence transfer from the mucosal to the serosal but not from the serosal to the mucosal baths. The ratio between the fluorescence intensities recorded with excitation wavelengths of 340 and 380 nm indicates that the calcium sensitive probe (free fura-2) was transferred to the serosal but not to the mucosal compartment by an oxytocin sensitive transport. (2) Preincubation with probenecid did not change fluorescence transfer in basal conditions but significantly reduced the oxytocin induced increase in free fura-2 transport. (3) Fluorescence accumulation inside the tissue was strongly reduced by oxytocin, but only when fura-2/AM was added to the mucosal side. (4) An osmotic gradient, in the presence of oxytocin, further increased the transfer of fluorescence at 380 nm but not at 340 nm. This indicated that the transfer of a calcium-insensitive fraction was being stimulated. (5) Preincubation with colchicine strongly inhibited fluorescence transfer across the tissue, at both 340 and 380 nm (the 340/380 ratio did not change). (6) Tissue accumulation was increased by colchicine. (7) Vanadate did not inhibit fura-2 transfer in the toad urinary bladder. We conclude that intracellularly-generated free fura-2 is only transported across the basolateral border, and that this transfer is stimulated by ADH. The calcium-insensitive fraction is transferred by a temperature-dependent process, sensitive to an osmotic gradient and colchicine. PMID- 8357815 TI - Electric field-mediated glycophorin insertion in cell membrane is a localized event. AB - Purified soluble glycophorin, an intrinsic protein, can be back 'electroinserted' in the membrane of Chinese hamster ovary cells by submitting the cell/protein mixture to short electric field pulses. Previous studies showed that this complex between pulsed cells and proteins, which is detected only when the cell membrane is electropermeabilized, was very stable. This strongly suggested that the protein was indeed inserted in the membrane. The basic processes involved in this phenomena are studied in the present work. The association is observed at the single cell level by means of videoimmunofluorescence. Electric field-mediated insertion occurs firstly in a limited patch of the cell surface, which size is in agreement with the prediction of Electropermeabilization theory. A free diffusion of the inserted proteins then follows on the cell surface. The diffusion coefficient is computed to be less than 10(-10) cm2/s as observed for transmembranous proteins. This slow process gives an homogeneous distribution of the inserted protein. PMID- 8357816 TI - The state of association of Band 3 of the human erythrocyte membrane: evidence of a hexamer. AB - Band 3 of the human erythrocyte membrane was isolated from 32P-labelled erythrocytes in non-ethyleneglycol n-dodecyl ether (C12E9), Triton X-100, and Brij 58 solutions, and its states of association were studied by sucrose gradient sedimentation and by Sepharose 4B column chromatography. The sedimentation and elution profiles indicated that Band 3 exists under two stable forms in each detergent solution, a slow form and a fast form. The fraction of the fast form in a Brij 58 solution was 2-3-times higher than those of the fast forms in C12E9 and Triton X-100 solutions. Moreover, depending of the conditions of isolation, only the slow form or the fast form was present in a Brij 58 solution. The apparent values of sedimentation coefficients, Stokes radii, and effective masses of the slow and fast forms in C12E9, Triton X-100, and Brij 58 solutions were determined. On the basis of these values, we have concluded that the slow and fast forms of Band 3 were dimer and tetramer in C12E9 and Triton X-100 solutions but were dimer and hexamer in a Brij 58 solution. PMID- 8357817 TI - Influence of hydroxylation and conjugation in cross-inhibition of bile acid transport across the human trophoblast basal membrane. AB - Taurocholate (TC) transport across the basal plasma membrane of the human trophoblast is a carrier-mediated process, whose specificity is probably not restricted to TC. The aim of this work was to gain further insight into the role of hydroxylation and conjugation in the behavior of the carrier system vs. bile acid (BA) species. Radiolabeled TC transport by basal plasma membrane (BPM) vesicles obtained from human term placenta was measured by a rapid filtration technique. Glycocholate (GC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TDC) inhibited TC binding to BPM. These bile acids compete with TC for the binding sites. Symmetry properties for GC- and TCDC-induced inhibition of TC transport was found in experiments where GC or TCDC were at the cis-side of the membrane (uptake and efflux experiments). GC and TCDC-induced inhibition seems to be of mixed type. By contrast, TDC was observed to affect TC transport differently, depending on whether the experiments addressed uptake or efflux. At the intracellular side of the membrane (uptake), TDC induced a marked increase in both Vmax and Kt. However, at the fetal side (efflux) a significant reduction in both Vmax and Kt was found. In spite of these peculiarities, the values for Ki were very close for GC, TCDC and TDC at the intracellular side but not at the fetal side, where the decreasing order for Ki was GC > TCDC > TDC. TC uptake by BPM vesicles was not modified in the presence of a wide range of estrone sulfate concentrations (0.002-1.0 mM). In summary, these results indicate that a particular bile acid molecular structure is necessary for steroid-related compounds to interact with the bile acid carrier located in BPM. They also suggest that changes in the number and position of hydroxy groups, as well as in the amino-acid moiety in amidated bile acids modify the behavior of the carrier, which may play an important role in the net vectorial transfer of bile acids across the placenta. PMID- 8357818 TI - Biosynthesis and initial processing of the cardiac sarcolemmal Na(+)-Ca2+ exchanger. AB - Based on the deduced amino-acid sequence of the cardiac Na(+)-Ca2+ exchanger, there are six potential N-linked glycosylation sites and a potential cleaved signal sequence. To study the post-translational modifications of the exchanger, in vitro translation was examined in the presence and absence of canine pancreatic microsomes. Glycosylation, detected as endoglycosidase H induced shifts in molecular size, was examined for proteins having different numbers of potential N-linked glycosylation sites by using full and partial length RNA transcripts. In the presence of microsomes, the molecular mass of the full-length clone increased from 110 to 113 kDa. Endoglycosidase H treatment led to a reduction to 108 kDa, indicating that glycosylation increases the molecular mass by approx. 5 kDa and a signal sequence of approx. 2 kDa is cleaved during processing. Analysis of molecular-mass shifts obtained with partial transcripts suggested that glycosylation occurs at position N-9. This was confirmed by site directed mutagenesis studies. A molecular mass of approx. 120 kDa was measured for Western blots of cardiac sarcolemmal membrane or oocytes expressing the wild type exchanger. The molecular mass was reduced by approx. 10 kDa for the N9Y mutant or from exchanger obtained from a baculovirus-infected insect cell line where glycosylation does not occur. The giant excised patch technique was used to determine the functional consequences of glycosylation. Na(+)-Ca2+ exchange current was examined in patches from oocytes expressing either the wild-type or N9Y mutant. The non-glycosylated mutant exhibited the same properties as the native exchanger with respect to voltage, sodium dependence, and the effects of chymotrypsin. The results indicate that glycosylation does not affect exchanger function in Xenopus oocytes and help to define exchanger topology. PMID- 8357819 TI - Interaction of hydrophobic peptides with model membranes: slow binding to membranes and not subtle variations in pore structure is responsible for the gradual release of entrapped solutes. AB - Investigation of the mechanism of action of membrane-perturbatory peptides often involves monitoring the release of entrapped solutes from small unilamellar vesicles. Complete release of vesicular contents can take 15 min or more. Theoretical calculations suggest that the process should be of the order of seconds and not minutes. We have investigated the membrane-perturbatory abilities of hydrophobic peptides corresponding to regions of pardaxin that are important for toxin action. Peptide-induced release of entrapped carboxyfluorescein (CF) from lipid vesicles under various conditions was monitored by fluorescence spectroscopy. Several minutes were required for the complete release of CF. This has been shown to be due to lack of instantaneous and complete association by all the added peptide with the lipid vesicles. In addition, for a given peptide/lipid molar ratio, an increase in lipid concentration causes an increase in the rate of CF-release. It is likely that increased binding following a greater number of collisions between peptide and vesicles is responsible for this observation. A Fast Protein Liquid Chromatography assay confirms that a significant amount of peptide remains unbound from the vesicles. Other investigators have reported the requirement for a similar time span for the complete release of vesicular contents by pardaxin and several other membrane-perturbatory peptide toxins. The proposed reason for the delay in lysis may therefore be applicable to a large variety of membrane-perturbants. Thus, the assay of peptide-induced release of vesicular contents is likely to predominantly reflect only the rate of association of peptide with the membrane, and not more subtle variations in the nature of the pore formed. PMID- 8357820 TI - In vitro cytostatic effect of TNF (tumor necrosis factor) entrapped in immunoliposomes on cells normally insensitive to TNF. AB - The cytostatic activity of TNF entrapped in novel immunoliposomes with a specific antibody against target cells is described. A two step conjugation method was used for the preparation of these targeted immunoliposomes. In the first step, liposomes containing N-4-(p-maleimidophenyl)butyryl phosphatidylethanolamine (MPB PE) were conjugated with a goat anti-mouse IgG Fab' fragment which recognizes the Fc portion of a mouse antibody against the target cell markers. In the second step, the mouse antibody against human tumor cells was conjugated to the liposomes. Using these targeted immunoliposomes, we demonstrated that cells usually insensitive to TNF such as Daudi cells, MT-2 cells and T-24 cells could become sensitive to TNF in vitro. The cytostatic activity of these immunoliposomes was blocked by the addition of a lysosomotropic agent such as NH4Cl or chloroquine. Significant uptake of 125I-TNF into T-24 cells was observed when these immunoliposomes were used, and this uptake of TNF was inhibited by cytochalasin B or chloroquine. Free 125I-TNF was not taken up by these cells. PMID- 8357821 TI - Novel radioactive phospholipid probes as a tool for measurement of phospholipid translocation across biomembranes. AB - In an attempt to develop a new method to measure transbilayer phospholipid translocation, with a higher sensitivity and higher temporal resolution, novel radioactive phospholipid probes (*C5-PC, *C5-PE, and *C5-PS) with a short acyl chain at the 2-position were synthesized. The *C5-PC probe was made by coupling lysophosphatidylcholine with [14C]pentanoic acid, using N,N-carbonyldiimidazole as a coupling agent (yield 37%), and *C5-PE and *C5-PS were synthesized by exchanging the choline moiety of *C5-PC for ethanolamine and L-serine, respectively, as catalyzed by phospholipase D. The usefulness of the probes was confirmed by measuring phospholipid translocation across the human erythrocyte plasma membrane, in which the presence of aminophospholipid translocase was revealed using EPR techniques (Zachowski, A., Farve, E., Cribier, S., Herve, P. and Devaux, P.F. (1986) Biochemistry 25, 2585-2590). Using the present probes, ATP-dependent and SH-reagent-inhibitable translocation of *C5-PS and *C5-PE from outer to inner leaflets, which is characteristic to the translocation mediated by aminophospholipid translocase, was detected with a higher sensitivity than seen with the EPR technique. These radioactive phospholipid probes will be useful to measure phospholipid translocation with a high sensitivity and have the potential for application in measurements of transbilayer lipid-translocation for a wide variety of membranes. PMID- 8357822 TI - Oligomeric structure of the sodium-dependent phlorizin binding protein from kidney brush-border membranes. AB - Immunodetection of solubilized kidney brush-border proteins on Western blots using antibodies against the 70 kDa phlorizin binding component of sodium-glucose cotransporter allows to identify an additional protein band with apparent molecular mass of 120 kDa in the presence of reducing agent dithiothreitol. Antibodies specifically eluted from the 70 kDa protein still recognize the 120 kDa protein on Western blot. The lack of dissociation of the 120 kDa protein from native brush borders or Triton X-100 extract in the presence of dithiothreitol can be improved by an extended incubation at 25 degrees C; this protein is full dissociated when purified by electroelution from polyacrylamide gel and gives two subunits with apparent molecular masses of 70 and 60 kDa by Coomassie staining and Western blot analysis. The effect of dithiothreitol on the renal brush-border membrane phlorizin binding is studied; a decrease in the number of high-affinity phlorizin binding sites without modification of the affinity to the binding molecule is observed. These data suggest that the high-affinity phlorizin binding moiety of sodium-glucose cotransporter exists in the kidney as a dimeric structure. PMID- 8357823 TI - The role of E2F in the mammalian cell cycle. PMID- 8357824 TI - Oncogenes and protein kinases in neuronal growth-factor action. PMID- 8357825 TI - Signals and genes in the control of cell-cycle progression. PMID- 8357826 TI - The tumor suppressor p53. PMID- 8357827 TI - Peptide growth factors and the regulation of early amphibian development. PMID- 8357828 TI - src-related protein tyrosine kinases and their surface receptors. AB - The CD4-p56lck and CD8-p56lck complexes have served as a paradym for an expanding number of interactions between src-family members (p56lck, p59fyn, p56lyn, p55blk) and surface receptors. These interactions implicate src-related kinases in the regulation of a variety of intracellular events, from lymphokine production and cytotoxicity to the expression of specific nuclear binding proteins. Different molecular mechanisms appear to have evolved to facilitate the receptor-kinase interactions, including the use of N-terminal regions, SH2 regions and kinase domains. Variation exists in stoichiometry, affinity and the nature of signals generated by these complexes in cells. The CD4-p56lck complex differs from receptor-tyrosine kinases in a number of important ways, including mechanisms of kinase domain regulation and recruitment of substrates such as PI 3 kinase. Furthermore, they may have a special affinity for receptor-substrates such as the TcR zeta, MB1/B29 or CD5 receptors, and act to recruit other SH2 carrying proteins, such as ZAP-70 to the receptor complexes. Receptor-src kinase interactions represent the first step in a cascade of intracellular events within the protein-tyrosine kinase/phosphatase cascade. PMID- 8357829 TI - The differential induction of alpha 1-acid glycoprotein and serum amyloid A genes by heavy metals. AB - We have investigated the differential regulation of the mouse (Balb/c) acute phase reactants, alpha 1-acid glycoprotein and serum amyloid A by heavy metals (Hg, Cd, Pb, Cu, Ni and Zn). Mice have two distinct alpha 1-acid glycoprotein mRNAs encoded by alpha 1-acid glycoprotein gene-1, (AGP-1) and alpha 1-acid glycoprotein gene-2 (AGP-2) and 3 distinct serum amyloid A mRNAs encoded by serum amyloid A gene-1, (SAA-1), serum amyloid A gene-2 (SAA-2) and serum amyloid A gene-3 (SAA-3). Using specific oligonucleotides as probes we have demonstrated that the AGP-1 and AGP-2 genes, and the SAA-1 and SAA-2 genes are differentially induced by heavy metals in the liver. At the peak of induction, AGP-2 mRNA is 80 100-fold higher than the AGP-1 mRNA level; the SAA-1 mRNA level is approx. 40 fold higher than SAA-2, and SAA-3 mRNA is not detected. A similar differential pattern of expression is observed in bacterial lipopolysaccharide mediated inductions. However, low levels of SAA-3 are also seen in this treatment. Adrenalectomy has no effect on the inductions by heavy metals of AGP-2 and the SAAs, indicating that the glucocorticoid receptor pathway may not function in this regulation. However, AGP-1 induction is significantly delayed, indicating that glucocorticoid may be essential for a rapid response to Hg. The liver is the major site of heavy metal induction of AGP and SAA genes; Hg induces AGP-1 and 2, and SAA-1 and 2 only in the liver. Our studies clearly show that the AGP and SAA genes belong to a subgroup of acute-phase reactants that respond to heavy metals. CRP is another member of this family. Furthermore, our data suggest that the mechanism is not directly mediated by glucocorticoid or cytokine induction pathways. PMID- 8357830 TI - Heat-shock-induced protein synthesis is responsible for the switch-off of hsp70 transcription in Tetrahymena. AB - We had previously described that new RNA synthesis is required for expression of the heat shock protein HSP70. Here, we find that the HSP70 mRNA decreases its levels under stress conditions, heat shock (HS) or arsenite (As), and that its levels start to decline at the same time as maximal HSPs synthesis (including HSP70) occurs. This suggests that regulation of the hsp70 gene is mainly exerted at the transcriptional level. Accumulation of the HSP70 mRNA in cells stressed in presence of cycloheximide (CHX), indicates that (a) protein(s) non-existent before stress, possibly HSP70 itself (which is shown here to be relatively stable), is involved in negatively regulating hsp70 expression. Since degradation of the HSP70 mRNA is also shown to occur in cells heat-shocked under CHX, as seen from decay of its levels upon addition of actinomycin D (AMD), the protein(s) must repress hsp70 expression at the transcriptional level. Other conditions that affect normal protein synthesis, namely the translation inhibitor puromycin and the arginine-analog canavanine (shown here to be stress inducers in Tetrahymena pyriformis), also cause a delay in transcription-arrest of the HSP70 mRNA. Under severe stress conditions of HS (36 degrees C) or As (350 microM), the levels of HSP70 mRNA are higher than under mild stress conditions, however, no significant difference is seen in the pattern of HSP70 mRNA decay. PMID- 8357831 TI - Isolation and characterization of a cDNA clone encoding for rat CSF-1 gene. Post transcriptional repression occurs in myogenic differentiation. AB - A major CSF-1 (Colony-Stimulating Factor 1) mRNA 4.0 kb long was expressed during the proliferation of the L6 alpha 1 rat myogenic cells and was down-regulated after their differentiation into myotubes. A complete cDNA encoding the rat CSF-1 gene (rmCSF-1) was isolated from a cDNA library of L6 alpha 1 myoblasts and sequenced. The overall deduced amino acid sequence was 100% and 68% identical to the mouse and human CSF-1, respectively. While the previously reported mechanisms about the regulation of CSF-1 expression in TPA-treated-monocytes (Horiguchi, J., Sariban, E. and Kufe, D. (1988) Mol. Cell. Biol. 8, 3951-3954) and in fibroblasts (Falkenburg, J.H.F., Harrington, M.A., De Paus, R.A., Walsh, M.K., Daub, R., Landegent, J.E. and Broxmeyer, H.E. (1991) Blood 78, 658-665) involved a control at the transcriptional level, in contrast, the CSF-1 mRNA (half-life approximately 3 h in L6 alpha 1 myoblasts) was post-transcriptionally down regulated during myogenesis. Inhibition of protein synthesis with cycloheximide (CHX) increased differentially the half-life of CSF-1 mRNA in L6 alpha 1 myotubes compared to L6 alpha 1 myoblasts. Finally, L6 alpha 1 myoblasts were shown to synthesize a 140 kDa homodimeric form of CSF-1. Thus, these findings, together with other results, indicate that CSF-1 gene products may play a role in the normal and neoplastic proliferation of muscular cells. PMID- 8357832 TI - Regulation of the uncoupled GTPase activity of elongation factor G (EF-G) by the conformations of the ribosomal subunits. AB - The elongation factor G (EF-G) GTPase activity is induced by either 70S ribosomes or 50S ribosomal subunits. The GTPase activity induced by 50S ribosomal subunits is predominant at low concentrations of monovalent cations and decreases with increasing concentrations of K+ or NH4+. Double-logarithmic plots of the data reveal straight lines with different slopes for low and high concentrations of monovalent cations, respectively, intersecting at the same concentration of monovalent cations where maximal EF-G GTPase activity is measured in the presence of both ribosomal subunits. Substantially the same curves are obtained when 50S ribosomal subunits are substituted by 50S CsCl-core particles partially reconstituted by addition of purified 50S split proteins L7/L12. Intact 30S ribosomal subunits, but not 30S CsCl-core particles are able to associate with 50S ribosomal subunits and to modulate ribosome-dependent EF-G GTPase activity. Therefore, our data clearly show that the biphasic courses of the NH4+ and K+ curves of EF-G GTPase activity induced by 50S ribosomal subunits are not due to contaminations with 30S ribosomal subunits but result from different conformations of EF-G/50S ribosomal-subunit complexes at low and high concentrations of monovalent cations, respectively. CD spectra of 50S ribosomal subunits measured under different salt conditions have shown that the conformation of the 50S ribosomal subunits is strongly dependent on the concentration of monovalent cations. The conformation of 30S ribosomal subunits is, however, considerably stronger influenced by the Mg2+ than by the concentration of monovalent cations. The salt effects on the conformation of the 30S ribosomal subunits correspond to the salt effects on the association of ribosomal subunits and the modulation of EF-G GTPase activity by 30S ribosomal subunits. Since, in the presence of both ribosomal subunits, EF-G GTPase activity is maximal at the same concentration of monovalent cations where obviously a spontaneous conformation change of 50S ribosomal subunits takes place, we postulate that EF-G GTPase primarily acts on the ribosomes by changing the conformation of 50S ribosomal subunits. The resulting model is based on the assumption that EF-G GTPase activity is considerably more strongly induced by the 'substrate conformation' ('state I') than by the 'product conformation' of the 50S ribosomal subunits ('state II'). A spontaneous transformation of 'state II' to 'state I' is expected to occur in the absence of mRNA, aminoacyl-tRNA and EF-T especially under salt conditions favouring state I. PMID- 8357833 TI - Purification and characterization of nuclear scaffold proteins which bind to a highly repetitive bent DNA from rat liver. AB - Our previous work (Hibino et al. (1992) Biochem. Biophys. Res. Commun. 184, 853 858) has shown that the binding affinities of a highly repetitive DNA component for rat nuclear scaffold proteins, P123 and P130, depend on the degree of sequence-directed bending of the helix axis. In the present experiment, these proteins have been purified and finally isolated by DNA-Sepharose column chromatography. The pI values of P123 and P130 were 7.2 and 8.1, respectively. The southwestern blotting revealed that a highly repetitive bent DNA (370-bp XmmI fragment) from rat liver binds readily to the isolated proteins under a hypotonic condition (50 mM NaCl) and that the level of the binding affinity for each protein was lowered with increasing NaCl concentration. The sedimentation analysis predicted that direct interaction between the XmnI fragment and P123 or P130 results in the formation of a complex which consists of two of the fragments and one molecule of the protein, alternatively, one of the fragment and three molecules of the proteins. Distamycin A, an antibiotic which binds specifically to AT-rich DNA, removed the bend in the XmnI fragment and inhibited binding of the fragment to P123 or P130, whereas neither removal of the bend nor binding inhibition was observed with chromomycin A3, an antibiotic specific for GC-rich sites in DNA. These results imply that AT-rich regions in a highly repetitive DNA component cause bending of the helix axis to be recognized by some of nuclear scaffold proteins. PMID- 8357834 TI - Molecular and biochemical characterization of a recombinant human PKC-delta family member. AB - Two cDNA clones coding for the human protein kinase C-delta (PKC-delta) were fortuitously isolated during the process of screening a human library for a cDNA clone of an unrelated protein, the nucleolar protein fibrillarin. The two human homologues have about 88% nucleotide sequence identity to the rat and mouse PKC delta cDNA clones. A comparison of the predicted amino acid sequences of the two human PKC-delta clones with the rat and mouse homologues indicated a greater degree of sequence divergence (89-90% homology) compared to the high degree of sequence conservation observed with other human PKC family members and their mammalian counterparts. Expression of the clones in the baculovirus insect-cell expression system indicated that both proteins exhibited phorbol ester binding activity, and were dependent upon phosphatidylserine and diacylglycerol for maximal activation. Further characterization of the properties of the human PKC delta revealed substrate and lipid dependencies distinct from other members of the protein kinase C family; including PKC-deltas isolated from other species. The dissimilarities in the predicted amino acid sequences between the human and other mammalian species could account in part for some of these observed biochemical differences. PMID- 8357835 TI - Cloning, sequencing and expression of the gene encoding NADH oxidase from the extreme anaerobic thermophile Thermoanaerobium brockii. AB - The gene encoding the enzyme NADH oxidase from the extreme thermophile Thermoanaerobium brockii has been isolated from a recombinant library of genomic DNA and sequenced. An open reading frame corresponds to the 651 amino acids of the enzyme's subunit, which include characteristic FAD- and NADH-binding sequences, as well as cysteines which are involved in the FeS cluster present in the enzyme. The enzyme is expressed either from its own promoter or from vector promoters in Escherichia coli. After heat-treating the recombinant extracts at 70 degrees C, most of the host proteins are denatured, leaving the NADH oxidase 5- to 10-fold enriched. PMID- 8357836 TI - Cloning and sequencing of a soybean nuclear gene coding for a chloroplast translation elongation factor EF-G. AB - A plant nuclear gene coding for a chloroplast specific translation elongation factor EF-G (cEF-G) was cloned and sequenced for the first time. We screened two partial soybean genomic libraries with a short PCR amplified pea DNA probe constructed according to the N-terminal peptide sequence of pea chloroplast EF-G. The gene is three times split, codes for a chloroplast type transit peptide and a protein very similar to bacterial translation elongation factor EF-G. The gene is expressed as evidenced by Northern hybridisations. PMID- 8357837 TI - The nucleotide sequence of human aminoacylase-1. AB - The nucleotide sequence of a cDNA coding for human aminoacylase-1 (N-acylamino acid aminohydrolase, ACY-1, EC 3.5.1.14) subunit has been determined. The amino acid sequence of human ACY-1 subunit deduced from its cDNA nucleotide sequence showed a high degree of identity (87.7%) with the corresponding protein from porcine [1], although the former is one amino acid residue longer than the latter. Of 12 histidine and 3 cysteine residues, conserved between the proteins from two species, some are anticipated to form the active site of ACY-1 as either catalytic residues or ligands for an essential Zn2+ atom. PMID- 8357838 TI - Structure and deduced amino acid sequence of the human fibromodulin gene. AB - We have determined the structure and partially sequenced the human fibromodulin gene. The translated region of the gene is composed of two exons. An exon in the 5'-non translated region is separated from the next exon by a 1 kb intron. This exon, which encodes the major part of the translated region, is 983 bp and is followed by an approx. 5 kbp intron. The last 50 nucleotides of the translated region as well as the 3'-nontranslated region are located on the last exon. This exon arrangement is different from the arrangement reported for the gene of the structurally related biglycan. The translated region of the gene was sequenced and compared with bovine fibromodulin. The amino acid sequences of human and bovine fibromodulin show an overall homology of 90%. PMID- 8357840 TI - Sequence and genomic organization of the Drosophila proteasome PROS-Dm25 gene. AB - The genomic region encoding the Drosophila proteasome alpha-type subunit Dm25 has been isolated and analysed with regard to its nucleotide sequence and structure. Our data show that the Dm25 coding region is interrupted by four introns and that the 5' upstream region contains no sequence motifs common with the two previously described proteasome genes. PMID- 8357839 TI - Nucleotide sequence of cDNA encoding ZP3 alpha, a sperm-binding glycoprotein from zona pellucida of pig oocyte. AB - We isolated a cDNA encoding the pig oocyte zona pellucida protein ZP3 alpha from a pig ovary lambda gt11 cDNA library. The 1699 bp cDNA contains a short 3' untranslated region characteristic of cDNAs encoding zona proteins. The deduced amino acid sequence for ZP3 alpha consists of 536 amino acid residues and shares 66% overall identity with a 55 kDa rabbit zona protein. Important features of the ZP3 alpha polypeptide include a predicted N-terminal signal sequence, twenty-two cysteine residues, an O-glycosylated domain and potential attachment sites for five N-linked sugar chains. A multibasic tetrapeptide occurs upstream of a predicted C-terminal transmembrane sequence; this suggests proteolytic processing of an integral membrane precursor within the constitutive secretory pathway. PMID- 8357841 TI - Cloning, expression and characterization of horse L-ferritin in Escherichia coli. AB - Horse L-ferritin cDNA was cloned from horse liver, and the base sequence was determined. The L-ferritin was expressed using pTZ18U encoding lac promoter, and found to possess an additional 8-amino acid sequence at the N-terminus as compared with commercially obtained horse spleen (natural) ferritin. It was determined that there was Pro at position 94 in both the recombinant and natural L-ferritin, although it was previously reported that Leu was in this position in the natural species. Transmission electron microscopy showed that this recombinant ferritin formed a 24-mer shell. PMID- 8357842 TI - Recent developments in certain X-linked genetic eye disorders. AB - Over the past few years, genetic diseases of the ocular system have become very active and fast-growing research areas in the vision field. The rapid development of the recombinant DNA techniques together with somatic cell genetics, during the last two decades has fueled this progress. As a result, many genetic disease genes have been localized in the human chromosome and several of them have been isolated and characterized. These and other studies have profoundly enriched our basic understanding of genetic eye disorders. Although gene replacement therapy, prenatal diagnosis and carrier detection have not been extensively tried for genetic eye diseases, such attempts will now be feasible. Molecular analyses made it clear that there are many challenging problems that need attention. This report highlights some of these initial developments, particularly on the X linked major genetic eye diseases. In order to help the beginners and general audience, a brief description of the clinical pathology and the molecular probes used to locate the genetic defects of certain disorders are presented. Disorders are arranged according to their linkage from telomere to telomere on the chromosome to give a coherent structure. It is hoped that this information is useful and of general interest for the beginners, established investigators and ophthalmologists. PMID- 8357843 TI - Polyamines in testosterone-induced hypertrophic and antifolate-induced hyperplastic mouse kidney. Differential effect of alpha-difluoromethylornithine. AB - In the testosterone-induced hypertrophic and antifolate (N10-propargyl,5,6 dideazafolic acid, CB 3717)-induced hyperplastic mouse kidney models, a marked increase of two diamine levels--putrescine and cadaverine--occurred which paralleled induced ornithine decarboxylase (ODC) activity. Under these conditions the augmentation of spermidine levels was much smaller, while spermine levels were affected differentially--increased by testosterone and decreased by CB 3717; this resulted in an increase of spermidine/spermine ratio in hyperplastic, but not hypertrophic kidney. alpha-Difluoromethylornithine (DFMO) prevented testosterone- or CB 3717-induced increment of both diamine levels. Spermidine and spermine depletion in response to DFMO was significant in hyperplastic kidney only. DFMO also significantly affected the other biochemical markers of hyperplasia, namely lowered CB 3717-induced cell proliferation rate and increased S-adenosylmethionine decarboxylase (AdoMetDC) activity. In contrast, testosterone induced hypertrophy was not influenced by DFMO, as judged by the lack of its effect on S-adenosylmethionine synthetase and cystathionine and synthase activity. These results indicate that the increase of putrescine levels does not mediate testosterone-induced renal hypertrophy and possibly also antifolate induced hyperplasia. The involvement of spermidine in mediation of renal hyperplasia is highly possible, while that of spermine is excluded. PMID- 8357844 TI - Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme. AB - Sandhoff disease is a lysosomal storage disorder characterized by accumulation of GM2 ganglioside due to mutations in the beta-chain of beta-hexosaminidase. Hexosaminidase activity is negligible in infantile Sandhoff disease whereas residual activity is present in juvenile and adult forms. Here we report the molecular basis of the first described adult form of Sandhoff disease. Southern analysis of chromosomal DNA indicated the absence of chromosomal deletions in the gene encoding the beta-chain. Northern analysis of RNA from cultured fibroblasts demonstrated that at least one of the beta-chain alleles was transcribed into normal-length mRNA. Sequence analysis of the entire cDNA prepared from poly adenylated RNA showed that only one point mutation was present, consisting of a G ->A transition at nucleotide position 1514. This mutation changes the electric charge at amino acid position 505 by substitution of glutamine for arginine in a highly conserved part of the beta-chain, present even in the slime mold Dictyostelium discoideum. The nucleotide transition generated a new restriction site for DdeI, which was present in only one of the alleles of the patient. Reverse transcription of mRNA followed by restriction with DdeI resulted in complete digestion at the mutation site, demonstrating that the second allele was of an mRNA-negative type. Transfection of COS cells with a cDNA construct containing the mutation but otherwise the normal sequence resulted in the expression of a labile form of beta-hexosaminidase. These results show that the patient's is a genetic compound, and that the lability of beta-hexosaminidase found in this form of Sandhoff disease is based on a single nucleotide transition. PMID- 8357845 TI - Ceramide composition of the psoriatic scale. AB - This paper investigates the ceramide composition of the psoriatic scale compared with that of normal human SC. A method was optimalized, based on TLC separation followed by densitometry, allowing the provision of good resolution and quantification of ceramide fractions from both normal and pathological specimens. Seven ceramide fractions were isolated and submitted to compositional analysis. The obtained results suggested a revisitation of previous ceramide designation. Therefore a simple classification is suggested, based on grouping ceramides carrying structural similarities under common codes. According to these rules, ceramides were grouped into five classes designated as: (1) Cer[EOS], which contains ester-linked fatty acids, omega-OH fatty acids and sphingosines; (2) Cer[NS], which contains non-OH fatty acids and sphingosines; (3) Cer[NP], which contains non-OH fatty acids and phytosphingosines; (4) Cer[AS], which contains alpha-OH fatty acids and sphingosines; (5) Cer[AP], which contains alpha-OH fatty acids and phytosphingosines. Analysis of ceramides from the psoriatic scale, compared to those from normal human SC, resulted in an impairment of the Cer[EOS] content as well as of the ceramides containing phytosphingosine, with concurrent increase in ceramides containing sphingosine, being the total amount maintained identical. Since one of the suggested pathways for phytosphingosine biosynthesis involves the water addition to the corresponding sphingosine double bond, we can speculate that the observed alteration is due to a deranged water bioavailability, associated with psoriasis. PMID- 8357846 TI - Renal corticosterone 6 beta-hydroxylase in the spontaneously hypertensive rat. AB - Excess 6 beta-OH-corticosterone production by family 3A cytochromes P-450 may play a role in genesis of hypertension in the spontaneously hypertensive rat (SHR), by producing a renal defect in Na+ excretion. Renal cytochromes P-450 may be a causal factor in this genetic model. Since family 3A P-450 is present in rat kidney (collecting duct), the renal family 3A catalytic (6 beta-OHase) and immunoreactive activities were compared in SHR and normotensive control (Wistar Kyoto; WKY) rats. Corticosterone 6 beta-hydroxylation is markedly higher in SHR than in WKY renal microsomal preparations. Western blot analysis with antibodies to rat and rabbit liver family 3A isoforms demonstrated related proteins. Densitometry revealed greater relative intensity of staining in SHR compared to WKY with both antibodies. Both antibodies inhibited corticosterone 6 beta hydroxylation by SHR renal microsomes. Increased renal 6 beta-OH-corticosterone production by increased renal family 3A cytochromes P-450 may play a role in the blood pressure elevation in SHR. PMID- 8357847 TI - Structural and functional studies in vitro on the p6 protein from the HIV-1 gag open reading frame. AB - Protein p6 from HIV-1 gag open reading frame is reported to affect both the final phase of assembly of the viral particle and the early stage of the gag polyprotein maturation in vitro. Two separate hypotheses have been proposed, on only one of these reported effects. We think that both observations may be eventually explained if p6 protein strongly inhibits the HIV-1 proteinase. Protein p6 was synthesised by solid-phase peptide synthesis. Several methods of folding the p6 protein were tested, each resulting in the random structure according to both CD and 1D proton NMR spectra. A uniformly high exposure of NH protons to the solution was confirmed by temperature-dependent NMR spectra and isotope exchange experiments. Thus the p6 protein does not have any rigid conformation in solution. A rigid structure is not formed after further cleavage by HIV-1 proteinase as neither the protein nor its fragments are cleaved by this proteinase. In addition, the p6 protein itself does not act as inhibitor of HIV-1 proteinase. This excludes a direct role of p6 protein and supports the hypothesis that p6 is involved in forming the appropriate structure of gag polyprotein precursor. The role of slowly cleaved tight gag-proteinase in the final stage of maturation may be to slow down maturation of the precursor polyproteins prior to their transport to final location in the membrane. PMID- 8357848 TI - A carbon-13 nuclear magnetic resonance investigation of the metabolic fluxes associated with glucose metabolism in human erythrocytes. AB - We have used [2-13C]D-glucose and carbon-13 nuclear magnetic resonance (NMR) spectroscopy to investigate metabolic fluxes through the major pathways of glucose metabolism in intact human erythrocytes and to determine the interactions among these pathways under conditions that perturb metabolism. Using the method described, we have been able to measure fluxes through the pentose phosphate pathway, phosphofructokinase, the 2,3-diphosphoglycerate bypass, and phosphoglycerate kinase, as well as glucose uptake, concurrently and in a single experiment. We have measured these fluxes in normal human erythrocytes under the following conditions: (1) fully oxygenated; (2) treated with methylene blue; and (3) deoxygenated. This method makes it possible to monitor various metabolic effects of stresses in normal and pathological states. Not only has 13C-NMR spectroscopy proved to be a useful method for measuring in vivo flux through the pentose phosphate pathway, but it has also provided additional information about the cycling of metabolites through the non-oxidative portion of the pentose phosphate pathway. Our evidence from experiments with [1-13C]-, [2-13C]-, and [3 13C]D-glucoses indicates that there is an observable reverse flux of fructose 6 phosphate through the reactions catalyzed by transketolase and transaldolase, even in the presence of a net flux through the pentose phosphate pathway. PMID- 8357849 TI - Measurement of fluxes through the pentose phosphate pathway in erythrocytes from individuals with sickle cell anemia by carbon-13 nuclear magnetic resonance spectroscopy. AB - Erythrocytes from individuals with sickle cell anemia have previously been shown to have increased levels of intracellular oxidants and increased oxidative damage. Oxidative damage has been implicated in the events leading to the painful crises and hemolytic anemia found in sickle cell anemia. Since the pentose phosphate pathway (PPP) is an important source of reducing capacity in erythrocytes, we have investigated the fluxes through the PPP in normal and sickle cell erythrocytes using [2-13C]D-glucose and carbon-13 nuclear magnetic resonance (NMR) spectroscopy. Our results indicate that sickle cell erythrocytes have a flux through the PPP of 0.13 +/- 0.02 mumol/h per ml erythrocytes that is comparable to that in normal erythrocytes, 0.21 +/- 0.02 mumol/h per ml erythrocytes. However, when stimulated with methylene blue, sickle cell erythrocytes show a decreased response, 0.59 +/- 0.10 mumol/h per ml erythrocytes, compared to normal erythrocytes, 1.64 +/- 0.10 mumol/h per ml erythrocytes. When homogeneous populations of sickle cell erythrocytes are isolated by density gradient centrifugation, the rate of flux through the PPP in methylene blue-stimulated sickle cell erythrocytes, 1.16 +/- 0.16 mumol/h per ml erythrocytes, approaches that in methylene blue-stimulated normal erythrocytes. In addition, by analyzing the dose response to methylene blue, we have found that the decreased stimulation of the PPP by methylene blue in heterogeneous populations of sickle cell erythrocytes is a failure of methylene blue to stimulate the PPP rather than a deficiency in the PPP in sickle cell erythrocytes. PMID- 8357850 TI - Fibronectin fragments bind to and penetrate cartilage tissue resulting in proteinase expression and cartilage damage. AB - We have reported that fibronectin (Fn) fragments added to bovine articular cartilage slices in culture causes marked cartilage damage by enhancing proteinase expression and resultant degradation and release of proteoglycan (PG). Several different non-overlapping Fn fragments, an amino-terminal 29-kDa, gelatin binding 50-kDa and integrin-binding 140-kDa Fn fragment, representing nearly all of the polypeptide chain, were compared in terms of ability to cause PG release from cartilage and to bind cartilage. The most active fragment, the 29-kDa fragment, was able to enter cartilage in an intact metacarpophalangeal joint in culture and cause PG release at the same rate as with surgically cut cartilage. Further, when radiolabelled 29-kDa fragment was added to cartilage, a large proportion bound the intact articular surface, while a lesser amount diffused throughout the tissue matrix and concentrated in clusters near the mid-section of full thickness cartilage. The 29-kDa, 50-kDa, 140-kDa Fn fragments and Fn, respectively, showed PG degradation activities 9-, 6-, 2- and 1.1-fold that of control levels and bound cartilage to the extent of 180, 20, 18 and 2 pmol/100 mg cartilage, respectively. Therefore, the PG degradation activities were greatest for the smaller fragments, which bound to the greatest extent. The apparent Kd values for interaction of the 29-kDa, 50-kDa, 140-kDa fragments and Fn for cartilage tissue were about 1.2, 0.3, 0.1 and 0.02 microM, respectively, and the order was inversely related to PG degradation activities. We conclude that the smaller the Fn fragment, the greater the degradation activity and extent of binding to cartilage tissue, but the weaker the affinity. PMID- 8357851 TI - Biological distribution of 99mTc-labeled YIGSR and IKVAV laminin peptides in rodents: 99mTc-IKVAV peptide localizes to the lung. AB - Two laminin-derived peptides containing either YIGSR or IKVAV (single amino acid code) sequences were radiolabeled with 99mTc and their biological distribution evaluated in rodents. Both 99mTc-peptides cleared rapidly from the circulation though the kidney, and to a lesser extent, through the liver. 99mTc-YIGSR peptide did not accumulate in any organ examined in normal, tumored, and emphysemic mice. The 99mTc-IKVAV peptide localized within 10 min to the lung of normal animals, resulting in lung-to-blood ratios of approximately 23:1. The 99mTc-IKVAV peptide localized to lung after submicron filtration and after intraperitoneal injection, suggesting that particulates do not major role in localization. Pre-incubation of 99mTc-IKVAV peptide in whole blood decreased lung localization, suggesting that margination of radiolabeled cells does not play a major role in the lung localization. When 99mTc-IKVAV was injected into mice with tumored lungs (melanoma), the lung uptake was markedly increased (up to 20% injected dose higher than control lungs) at all time points examined (10, 30, and 120 min). When 99mTc-IKVAV was injected into mice with genetic emphysema, the lung uptake was markedly decreased at all time points. The localization of the 99mTc-IKVAV containing peptide to the lung is consistent with a receptor-based mechanism. PMID- 8357852 TI - Calpain activity alters in rat myocardial subfractions after ischemia or reperfusion. AB - To examine whether calpain is activated during ischemic or reperfusion injury, we measured calpain activity of the subfractions of rat myocardia after global ischemia for 60 min or the ischemia followed by 30 min reperfusion by the Langendorff procedure. The myocardial homogenate was fractionated into 600 x g, 10,000 x g and 100,000 x g pellet fractions as well as 10,000 x g supernatant fraction. The supernatant fraction was further subjected to DEAE cellulose and phenyl-Sepharose chromatographies to separate mu- and m-calpains. The m-calpain activity of the DEAE fractions after global ischemia for 60 min was higher but that after ischemia-reperfusion was lower than that of the control. On the other hand, the ischemia-reperfusion but not ischemia by itself raised the calpain activity of the phenyl-Sepharose fraction (mu-calpain) and the 10,000 x g pellet measured at 100 microM and 5 mM Ca2+. Treatment with verapamil but not with ryanodine during ischemia attenuated the increase in m-calpain activity. A dot blotting analysis of calpain antigenicity showed a decrease in soluble but no change in the particulate fractions after ischemia-reperfusion. An immunoblotting technique did not detect proteolysis of the calpain 80-kDa subunit. These observations suggest that calpain is activated by Ca2+ influx during ischemia and reperfusion without gross changes in its amount. Some unknown processes other than translocation or autolysis are thought to be involved in the alterations. PMID- 8357853 TI - Determination of an acetylcholinesterase inhibitor, MDL 73745, in dog plasma and urine by combined gas chromatography/negative ion chemical ionization mass spectrometry. AB - A highly sensitive and specific assay has been developed for the determination of MDL 73745 [2,2,2-trifluoro-1-(3-trimethylsilyl-phenyl) ethanone] (I) and the internal standard (MDL 74398) at the nanomolar level in dog plasma and urine by gas chromatography/mass spectrometry. After a single-step extraction process, an aliquot was directly injected onto the gas chromatograph column. The mass spectrometer was run in the negative ion chemical ionization mode with ammonia as reagent gas, and was set to monitor the abundant M-. ion at m/z 246 of both compounds. The method yielded a linear response over the concentration range 0.1 10 pmol 100 microliters -1 plasma or urine. Within-day reproducibility at a concentration of 0.25, 1 and 5 pmol 100 microliters -1 plasma was 8.6%, 1.0% and 1.0%, respectively. The method was applied to the determination of I in plasma and urine after administration of 1 mg kg-1 i.v. and 10 mg kg-1 p.o. to dogs. PMID- 8357854 TI - A simplified method for deuterium/hydrogen isotope ratio measurements on water samples of biological origin. AB - Equilibration of hydrogen gas with the water in a variety of biological sample materials was carried out in Vacutainers using platinum-on-alumina catalyst physically isolated from the liquid water. The equilibration takes 3 days at room temperature--much slower than with catalysts which float on the water surface- but this reduces the short-term temperature sensitivity of the procedure, and the inexpensive materials used allow convenient disposal of biologically contaminated samples after analysis. The slow equilibration also allows time for complete exchange with water contained in a complex sample matrix such as plant stems or soil without the need for prior isolation of the water sample. The method has particular application in studies of human total body water where repeated studies can be carried out over a short time period without the need to wait for the previous dose to wash out. Water turnover rates from total diurnal energy expenditure studies measured by this method were not significantly different from those obtained by the zinc reduction method. PMID- 8357855 TI - Quantitative measurement of 4-hydroxy tamoxifen in human plasma and mammary tumours by combined gas chromatography/negative chemical ionization mass spectrometry. AB - A highly sensitive and specific assay was developed for the quantitative measurement of 4-hydroxy tamoxifen (4-OH Tam) at the femtomole level in human plasma and mammary tumours. The drug and deuterated internal standard (4-OH Tam D4) were measured by gas chromatography/negative chemical ionization mass spectrometry with methane as the reactant gas. The two compounds of interest were isolated from the complex biological matrices using a solid-phase extraction procedure with Extrelut 1 columns. Soft operating conditions were required to convert 4-OH Tam to the fluorinated derivatives with pentafluorobenzyl chloride. The mass spectrometer was tuned to monitor the abundant and stable molecular ions at m/z 581 and 585 which were generated in the ion source by an electron capture process. This assay required only 0.5 ml of plasma or 0.5 g of mammary tissue, and the quantification limits of the method were 20 pg ml-1 for the body fluids or 100 pg g-1 for the tissue samples. The very low relative standard deviation and mean percentage error calculated during the different within-day or day-to day repeatability assays have clearly demonstrated the ruggedness of the technique for routine analysis of 4-OH Tam. PMID- 8357856 TI - Effect of the biological matrix on the urinary testosterone/epitestosterone ratio measured by gas chromatography/mass spectrometry in doping analysis. AB - Testosterone doping in sport is detected by measurement of an increased testosterone/epitestosterone (T/E) ratio in urine. The critical limit is 6. The present study concerns calibration curves for the T/E ratio measured by gas chromatography/mass spectrometry (electron impact) according to the guidelines of the International Olympic Committee. Testosterone (T) and epitestosterone (E) are measured as trimethylsilyl (TMS)-enol-TMS ethers in selected ion monitoring mode using m/z 432 with methyltestosterone (MT) (m/z 446) as internal standard. Calibration curves corresponding to T/E = 1, 6 and 12 prepared directly, i.e. without extraction of T and E, were non-linear. The non-linearity was caused by an increase of the relative molar response of T with respect to the internal standard MT with increasing concentration level. A mean increase of 82% was observed from T/E = 1 to T/E = 12 (E fixed). Adding T/E corresponding to 1/1, 6/1 and 12/1 to urine without endogeneous hormone content resulted in an almost linear calibration curve along the diagonal, with only a slight increase of the relative molar response of testosterone (16% from T/E = 1 to 12). Apparently, the biological matrix stabilizes the relative molar response over a wide concentration range. At a molar ratio of about 1/1 for T/MT, the relative molar response for direct measurement of T is identical to that observed in the presence of urine matrix, which is explained on the basis of a simple mathematical model. The practical conclusion of this study is that, contrary to the present-day practice, calibration curves for the T/E ratio should be based on T/E added to blank urine taken through the extraction procedure. Otherwise, the T/E ratio of urine sample is systematically easily underestimated by 30% or more. PMID- 8357857 TI - Plasma kinetics of magnesium and calcium stable isotope tracers in a human subject after simultaneous oral ingestion of 25Mg and 44Ca determined by thermal ionization mass spectrometry. AB - The plasma concentrations of stable isotope tracers of magnesium (25Mg) and calcium (44Ca) were determined during a 50 h period, after simultaneous oral tracer ingestion in an adult man. The measurements were performed by magnetic sector field mass spectrometry using surface ionization ion sources. The data were used to evaluate the potential of this method in long-term kinetic studies. It is concluded that under the experimental conditions specified, the isotopic tracers will be detectable in blood plasma with sufficient precision and accuracy for approximately 600 h after oral ingestion. The differences in the plasma concentration curves of 25Mg and 44Ca were analysed by means of the convolution integral method. These differences indicate inhomogeneities in the distribution of absorption activity relative to magnesium and calcium within the upper small intestine. PMID- 8357858 TI - Characterization of the primary structure of H-protein from Pisum sativum and location of a lipoic acid residue by combined liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry. AB - A purified extract of H-protein, a subunit of the glycine cleavage complex of the pea leaf mitochondria, was investigated by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS), using both continuous flow fast atom bombardment (CF-FAB) and electrospray ionization (ESI) mass spectrometry. Determination of the molecular weight of the entire protein, a 14 kDa subunit of the glycine decarboxylase complex, was achieved by ESI mass spectrometry and revealed covalent binding of the protein to the stabilizing agent beta-mercapto-ethanol. On-line LC/MS analysis of peptides arising from the endoproteinase Glu-C digestion of the H protein was achieved using capillary columns (0.25 mm i.d.), and permitted confirmation of the previously reported sequence deduced from cDNA cloning experiments. The detailed interpretation of data extracted from these LC/MS experiments facilitated identification of peptides containing modified amino acid residues. In particular the identification of a lipoic acid cofactor, a rather unusual modified lysine residue which interacts with different active sites in the enzyme complex, was achieved using both LC/CF-FAB-MS and LC/ESI-MS. The exact location of this modified lysine residue was determined by obtaining fragment spectra of multiply protonated precursor ions of selected peptides, using on-line LC/MS/MS techniques. PMID- 8357859 TI - Gas chromatographic/electron impact mass spectrometric selective confirmatory analysis of clenbuterol in human and bovine urine. AB - A method for the confirmatory analysis of clenbuterol in human and bovine urine was developed. After a double washing of the acidified sample with tert-butyl methyl ether (only for bovine urine), and a solid-phase extraction with Bond-Elut Certify columns, derivatization was performed with trimethylboroxine. The extract was then analysed by gas chromatography/electron impact mass spectrometry. The advantages of the methylboronate derivative with respect to other derivatives are discussed in terms of chromatographic properties and, above all, of specificity of the electron impact mass spectrum. The method was successfully used for the confirmatory analyses of clenbuterol during the XXV Olympic Games of Barcelona. PMID- 8357860 TI - Low-energy fast atom bombardment tandem mass spectrometry of monohydroxy substituted unsaturated fatty acids. AB - The low-energy collision-induced dissociation (CID) of the carboxylate anions generated by fast atom bombardment ionization of monohydroxy unsaturated fatty acids derived from oleic, linoleic, linolenic and arachidonic acids were studied in a tandem quadrupole mass spectrometer. The collisional activation spectra revealed structurally informative ions as to the position of the hydroxyl substituent in relationship to the sites of unsaturation. Five mechanisms are proposed for the fragmentation of hydroxyl substituted unsaturated fatty acids and are dependent upon the presence of alpha- or beta-unsaturation sites. These mechanisms include charge-remote allylic fragmentation, charge-remote vinylic fragmentation, charge-driven allylic fragmentation, charge-driven vinylic fragmentation, and homolytic fragmentation by an oxy-Cope rearrangement process. The assignment of specific fragmentation pathways was supported in many instances with deuterium-labeled analogs. Although no single fragmentation mechanism appears to predominate, a rational approach to the interpretation of these CID spectra is proposed. The CID spectra of unknown compounds could be used to establish the hydroxyl substituent position in relationship to certain sites of unsaturation but would not be indicative of all double bond locations. The oxy Cope rearrangement is specific for a structural unit, namely the 3-hydroxy-1,5 diene moiety. PMID- 8357861 TI - Determination of linkage positions in peracetylated (methyl) xylo oligosaccharides with fast atom bombardment mass spectrometry. AB - Distinction between the linkage types 1-->2, 1-->3 and 1-->4 of xylobioses can be achieved on the basis of the unimolecular decomposition spectra of the oxonium ions of the per-O-acetylated methyl glycosides. The spectra of the oxonium ions of various unbranched xylotri-, tetra- and pentaoses allow determination of the linkage position between the xylose residues. This indicates that in unbranched peracetylated xylo-oligosaccharides the linkage between the xylose residues at the non-reducing end can be determined. PMID- 8357862 TI - Concentration dependence of methyl palmitate isotope ratios by electron impact ionization gas chromatography/mass spectrometry. AB - Isotope ratios must be measured precisely when stable isotopic tracers are used for in vivo metabolic kinetic studies since low enrichments are generally achieved above relatively high natural abundance backgrounds. We have observed that the (m + 1)/(m + 0) isotope ratio for the molecular ion of methyl palmitate (measured by electron impact ionization selected ion monitoring gas chromatography/mass spectrometry) is limited by a dependence of the isotope ratio on the quantity of sample analyzed. Since it is not practical to analyze exactly the same quantity of sample in a series of samples, this concentration dependence decreases the apparent precision of the isotope ratio measurement. The apparent natural abundance (m + 1)/(m + 0) isotope ratio increased from approximately 0.185 (0.2 nmol analyzed) to 0.20 (2.0 nmol). The concentration dependence was not altered as the quadrupole tuning resolution was varied and did not appear to arise from system non-linearity. The major source of concentration dependence derived from hydrogen abstraction during ion-molecule collisions within the ionization chamber. The concentration dependence was decreased as the repeller voltage increased and ion residence times in the source were reduced. Furthermore, the integrated (m + 1) peak ares increased with the square of the (m + 0) peak area, consistent with a bimolecular ion-molecule collision process. A simple mathematical correction for the concentration dependence afforded a ten fold improvement in the coefficient of variation of the isotope ratio measurement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357863 TI - 750 MHz 1H-NMR spectroscopy of human blood plasma. AB - The application of high-resolution 750 MHz 1H-NMR spectroscopy to a biological fluid is demonstrated for the first time and its advantages over 600 MHz 1H observation shown by reference to studies on human blood plasma. Improvements in signal dispersion were observed which facilitated improved signal assignments. Differences in lipid/lipoprotein signal line-widths between 600 and 750 MHz were noted indicating that ultrahigh field measurements may help to give insight into dynamic motional phenomena of lipids in whole plasma. The two-dimensional J resolved (JRES) technique and spin-echo spectra measured at 750 MHz have enabled new signal assignments to be made in control plasma. The application of 750 MHz JRES to the clinical chemical problem of the detection of abnormal metabolites associated with chronic renal failure is also demonstrated. PMID- 8357864 TI - Solid-phase extraction of 1,4-benzodiazepines from biological fluids. AB - The solid-phase extraction (SPE) of seven 1,4-benzodiazepines (oxazepam, diazepam, temazepam, nordazepam, brotizolam, adinazolam and midazolam) using prazepam as internal standard was investigated. The 1,4-benzodiazepines were recovered from an aqueous buffer of suitable pH, using C18 Sep-Pak cartridges and mixtures of methanol-water as elution solvent. The recovery of oxazepam using different sorbent materials (C2, C8, C18, cyanopropyl, phenyl and cyclohexyl Bond Elut) was also examined as a function of pH and the composition of the elution solvent. The SPE of oxazepam was investigated using spiked urine samples and the C2 cartridge gave rise to the cleanest urine extracts. The recoveries of the other 1,4-benzodiazepines from spiked urine and plasma samples using the C2 cartridge was then found to be higher than 90%, without any interference from endogenous compounds of the samples. Finally, the influence of other factors such as drug concentration, sample volume and the number of times the SPE cartridge had been used was also examined. PMID- 8357865 TI - Optimization of the USP assay for hyaluronidase. AB - The current USP XXII assay for hyaluronidase (EC 3.2.1.35, HAse) determines activity indirectly by measuring the amount of undegraded hyaluronic acid (HA) substrate remaining after the enzyme is allowed to react with the HA for 30 min at 37 degrees C. To be acceptable as a substrate, the HA must pass a USP suitability test. In this study, seven HA samples, which differed in their anatomical origin, their commercial supplier, and their chondroitin sulphate content, were tested as substrates. One of these did not pass the USP suitability test and therefore would not be an officially acceptable substrate; however, it was carried through the investigation along with the others in order to demonstrate its effect on the analysis. All seven HAs were used as substrates to assay testicular hyaluronidases from three different suppliers. The standard by which the other hyaluronidase activities were measured was USP hyaluronidase reference standard. The activity values calculated for a particular hyaluronidase differed significantly depending on which HA was used as substrate in its assay. Optimal results, as judged on the bases of initial purity, suitability for the assay, linearity of the standard curve, and per cent relative standard deviation of the measured activity, were obtained with a HA substrate derived from vitreous humour. PMID- 8357866 TI - Characterization of polymorphs of a new anti-inflammatory drug. AB - The present study demonstrates the utility of a diversified analytical approach for the characterization and quantitative analysis for two polymorphs of a new anti-inflammatory agent, (+/-)-7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy 3,4-dihydro -8-propyl- 2H-1-benzopyran-2-carboxylic acid (SC-41930). The existence of two distinct crystal polymorphs of SC-41930 was qualitatively indicated through microscopy and application of thermal methods of analysis. The application of TGA was important for establishing that the two solid forms were, in fact, polymorphs, as opposed to solvated and unsolvated drug substances. The application of IR spectrometry revealed spectral features in the carbonyl stretching region, which were characteristic and unique to the two SC-41930 polymorphs. DRIFT spectrometry was implemented as the sampling method of choice to eliminate the possibility of polymorphic transformations during conventional mulling or KBr pellet sampling procedures. The DRIFT spectrometry procedure permitted development of a quantitative assay for detection of the low-melting polymorph (as an impurity) in high-melting samples. Calibration plots showed acceptable linearity of response from 0 to 25% (w/w) low-melting samples spiked into the high-melting polymorph. The performance characteristics of the method indicated good run-to-run and day-to-day consistency for its intended use. PMID- 8357867 TI - Automatic determination of amylocaine and bromhexine by atomic absorption spectrometry. AB - An automatic method for the determination of amylocaine and bromhexine hydrochloride by atomic absorption spectrometry (AAS) is proposed. The drugs were determined indirectly by formation of reineckates, extraction into 1,2 dichloroethane and measurement of chromium in the organic phase. The chemical conditions and experimental variables influencing the performance of the flow system of the liquid-liquid extractor were established. The proposed method allows the determination of amylocaine and bromhexine at concentrations between 3 and 120 micrograms ml-1 with a relative standard deviation of 1 and 3%, respectively, even in the presence of other synthetic drugs. PMID- 8357868 TI - An automated aerosol actuator: application to the uniformity testing of pharmaceutical aerosol dosage forms. AB - An automated system for valve performance testing to determine net weight loss per actuation of pharmaceutical aerosol dosage forms has been developed and is described. The principal element of the system is a novel automatic aerosol actuation device. Details of the validation, comparison to manual methods of analysis and advantages are presented. The automated system has been shown to be a cost-effective, productive and facile alternative to manual testing. PMID- 8357869 TI - GC-MS procedure for the analysis of zipeprol. AB - A sensitive and specific quantitative method for the determination of zipeprol, a newly abused antitussive, in human fluids is described. Zipeprol and an internal standard, levallorphan, are isolated by a basic extraction and back-extraction process. The final extract is derivatizated with BSTFA + 1% TMCS and separated on a 12-m HP-1 capillary column. Drugs are detected by selected ion monitoring at m/z 335 and m/z 355 for zipeprol and the internal standard, respectively. The minimum detectable quantities are 0.6 and 0.4 ng ml-1, for zipeprol in plasma and urine, respectively. Relative standard deviations for within-run data are less than 6%. PMID- 8357870 TI - Influence of hydrolysis procedures on the urinary concentrations of codeine and morphine in relation to doping analysis. AB - A method is described for the GC-NPD determination of urinary codeine and morphine after derivatization with trifluoroacetic anhydride. The lower limit for accurate quantitative determination was 0.05 microgram ml-1. After the oral administration of Bisolvon Griblettes corresponding to 30 mg codeine phosphate to seven subjects maximum codeine concentrations were obtained after 1-2 h and codeine remained detectable generally 24 h post dosing. The mean maximum level was 5.1 +/- 2.8 micrograms ml-1 found after enzymatic hydrolysis with Suc Helix pomatia juice (SHP). Based on these and previous results (mean 6.3 +/- 3.4 micrograms ml-1) a threshold level for codeine of 16 micrograms ml-1 is proposed. Significant differences were noticed between urinary codeine concentrations found after enzymatic hydrolysis with SHP, beta-glucuronidase from Patella vulgata and acid hydrolysis, respectively. Generally, highest values were obtained after SHP, while beta-glucuronidase and especially acid hydrolysis resulted in much lower levels. No morphine could be detected after acid hydrolysis. Concerning doping analysis, in particular the uniformity of methods and interpretation of the results, it is recommended that the hydrolysis method should be specified in the rules of those sporting federations allowing codeine and/or morphine. PMID- 8357871 TI - Liquid chromatographic study of the stability of 5-halogeno-2'-deoxyuridines. AB - The stability of a series of 5-halogeno-2'-deoxyuridines was investigated using liquid chromatography as the analytical technique. Characteristics and profiles of the acidic, neutral and alkaline degradation are described, together with Arrhenius relationships and activation parameters for weakly acidic media. PMID- 8357872 TI - Assay of citrate in pharmaceutical matrices by indirect photometric liquid chromatography. AB - The development of a simple HPLC procedure is described for the analysis of citrate in pharmaceutical formulations using the technique of indirect photometric chromatography. A novel mobile phase, using dual eluent species, was developed for rapid elution of citrate. The developed method was found to be linear over the range studied (1-12 micrograms of citrate injected), showed good per cent recoveries (+/- RSD) of 97.5 +/- 3.05% from a generalized matrix solution, and includes very simple sample preparation steps for analysis of commercial products. This method is quite specific for tricarboxylic acids as most other ions are not retained by the column using the developed mobile phase. The resolution of the method is also good as indicated by a baseline resolution (Rs = 1.5) obtained for citrate and tricarballylate, two structurally similar tricarboxylic acids. It is proposed that the developed method be evaluated as an alternative to the tedious procedures employed by the USP for assay of total citrate in some of its monographs. PMID- 8357874 TI - Determination of ampicillin in human plasma by high-performance liquid chromatography using ultraviolet detection. AB - A high-performance liquid chromatographic method with isocratic elution has been developed for the determination of ampicillin in human plasma. The method comprises injection of the plasma after protein precipitation on to a reversed phase C18 column, using phosphate buffer (pH3.5)-methanol as the mobile phase. The method involves UV detection at 225 nm. This method provides a simple technique for the rapid analysis of ampicillin within the concentration range 0.2 25 micrograms ml-1 with a high degree of accuracy and precision. PMID- 8357873 TI - Comparison of separation and detection techniques for human growth hormone releasing factor (hGRF) and the products derived from deamidation. AB - Separation of the deamidation products, Asp8 Leu27 hGRF(1-32)NH2 (MH+ = 3654) and isoAsp8 Leu27 hGRF(1-32)NH2 (MH+ = 3654), from the parent analogue Leu27 hGRF(1 32)NH2 (MH+ = 3653) was achieved by reversed-phase LC and CE, where the retention order was seen to change from tr isoAsp8 hGRF < tr Asn8 hGRF < tr Asp8 hGRF to tr Asn8 hGRF < tr Asp8 hGRF < tr isoAsp8 hGRF, respectively. Both reversed-phase LC and CE gave adequate separations, limits of detection and standard curves. However, CE was preferred due to shorter analysis time, better separation and a smaller demand for material. Packed capillary LC with ESI-MS was then compared with UV detection. On-line LC-MS was found to offer the most efficient approach to detection and identification of hGRF analogues within a single methodology. Identification of Asn8 hGRF from the isobaric deamidation products was achieved from analysis of the triply charged states, where the species were separated by 0.5 amu. LC-MS separation and identification of degradation products offers a viable alternative to fraction collection and subsequent sequencing or enzymatic identification methods. The method becomes increasingly useful for such cases as trace degradation product identification, minimal sample availability or instability of resulting degradation products. PMID- 8357875 TI - Simultaneous determination of a new anticancer drug galocitabine and its metabolites in blood by high-performance liquid chromatography. AB - A relatively simple and sensitive high-performance liquid chromatographic (HPLC) method is described for measuring galocitabine (Ro 09-1390) and its meatbolites, i.e. 5'-deoxy-fluorocytidine (5'-DFCR), 5'-deoxy-fluorouridine (5'-DFUR) and 5 fluorouracil (5-FU), in blood for the purpose of studying pharmacokinetics and toxicokinetics in small animals. The procedure for blood includes deproteinization with acetonitrile. Blood components were separated on a reversed phase C18 column with a linear gradient of acetonitrile and water and detected at a wavelength of 270 nm. The between-day relative standard deviation (RSD) was less than 10% for all compounds at concentrations of 10-100 micrograms ml-1. The calibration curves obtained from the analysis of blood samples were linear and the correlation coefficients ranged from 0.997 to 0.999. The calculated determination limits were 6.9 micrograms ml-1 for galocitabine, 3.0 micrograms ml 1 for 5'-DFCR, 4.0 micrograms ml-1 for 5'-DFUR and 3.7 micrograms ml-1 for 5-FU. PMID- 8357876 TI - Modified high-performance liquid chromatographic method for analysis of drotaverine in human plasma. AB - An HPLC method is described for the determination of drotaverine in plasma; papaverine is used as the internal standard. The lower limit of quantitation is 50 ng ml-1 with an inter-assay precision (RSD) of below 4%. The method has been validated and successfully used to assay clinical trial samples in healthy volunteers. PMID- 8357877 TI - Measurement of ascorbic acid in human aqueous humour and plasma and bovine aqueous humour by high-performance liquid chromatography with electrochemical detection. AB - High-performance liquid chromatography (HPLC) on ODS silica with cetyltrimethylammonium bromide as an ion-pairing reagent and electrochemical detection (ECD) was used to determine ascorbic acid in bovine and human aqueous humour and human plasma. Hydroquinone was used as the internal standard. A calibration curve plotted with ascorbic acid concentrations in the range 0.5-5 micrograms ml-1 for peak height versus internal standard peak height had a correlation coefficient of 0.998. The RSD (precision) between analyses of the same diluted sample was 1.5% and the RSD (reproducibility) between analyses of separate aliquots of the same sample of aqueous humour was 1.6%. PMID- 8357878 TI - An improved extraction method for the HPLC determination of morphine and its metabolites in plasma. AB - A new, simple and rapid extraction procedure coupled with a combined coulometric fluorescence HPLC assay is described for the simultaneous determination of morphine (M) and morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), and normorphine (NM) in plasma. The effect of concentration and pH of selected ion pairing agents on the extraction of these compounds from plasma by solid-phase extraction was investigated. The extraction procedure was optimized in terms of recovery, reproducibility and lack of interference from endogenous materials. The optimized method uses tetrabutylammonium hydrogen sulphate (TBAHS) at pH 10 followed by separation on a single C18 solid-phase extraction cartridge. For routine analysis the procedure provides high and reproducible recoveries over a concentration range of 1.0-1000 ng ml-1 for morphine, M6G and normorphine and 20 1000 ng ml-1 for M3G. The method was used successfully to analyse plasma samples from a pharmacokinetic study in which sheep had received an intravenous dose of 0.015 mg kg-1 of M6G. PMID- 8357880 TI - [Assessment of portal hypertension in hepatic cirrhosis in relation to etiologic factors]. AB - Hundred-forty-one patients, 78 affected by alcoholic liver cirrhosis and 63 by posthepatitic cirrhosis were studied in order to assess the degree of portal hypertension in liver cirrhosis of different etiology taking into account the developing stages of the disease. Etiological assessment was based on anamnesis, laboratory data, needle liver biopsy and patients of each group were divided into 3 subgroups (grade A, B, C) according to Child-Turcotte classification. A > 1.3 cm diameter of portal vein and a > 13 cm spleen size evaluated by means of real time ultrasonography together with the occurrence of esophageal varices at endoscopy were considered as signs of portal hypertension. Our study shows that such signs are more frequent in patients affected by posthepatitic cirrhosis in comparison with those affected by alcoholic cirrhosis. If the severity of the disease was considered, at the early stage (grade A) no significant difference was reported in portal diameters while splenomegaly and esophageal varices appeared more frequent in posthepatitic cirrhosis. In grade B patients the increase of portal and spleen size proved significantly greater in posthepatitic cirrhosis whereas prevalence of esophageal varices was similar in the two groups. The lack of differences in the three considered parameters at the end stage of the disease may be due to severe changes in liver morphology actually similar in the 2 groups apart from etiological factors. PMID- 8357879 TI - Indirect determination of diphenhydramine hydrochloride by atomic absorption spectrometry. PMID- 8357881 TI - [Palliative endoscopic intubation of esophago-gastric neoplastic stenosis: analysis of factors that may influence immediate results]. AB - The paper examines a series of 172 patients undergoing endoscopic intubation with plastic stent due to unoperable esophago-gastric tumoral stenoses during the period 1980-1991. An analysis of the data enabled the following conclusions to be drawn: (1) The majority of perforations occur during the treatment of distal stenoses (15%), anastomotic stenosis (20%) and extrinsic compression stenoses (23% vs 7% in the case of stenosing primary esophageal neoplasia). (2) Severe respiratory problems may occur during treatment of cervical stenoses. (3) Malfunctioning of prostheses is more frequent in the treatment of cardias stenosis (10%). Having a few technical comments on the subject of passing the guide thread through the most twisting and narrow stenoses, the authors express the wish that expandable metal prostheses will be more widely used in order to render the method less traumatic, increase the percentage of success (extending the indications regarding the site and type of stenosis) and reduce severe complications. PMID- 8357882 TI - [Percutaneous endoscopic gastrostomy]. AB - Surgical gastrostomies were first performed in the middle of the 19th century and modified during the following years, but the most important technical improvement was percutaneous endoscopic placement (PEG), in 1980 by Ponsky and Gauderer. This technique doesn't require anesthesia and it in possible also in patients with contraindications to surgical gastrostomy. The simple procedure involves a shorter hospitalization, lower risks and reduced costs. Many authors already reported the good results of this new technique, that can be performed on a day hospital regimen as well. The main indications are head and neck cancers, neurologic diseases involving food intake capacity, cancer cachexia, obstruction of the GI tract when there is enough space for an endoscopic procedure. Every disease that can compromise food intake for a period longer than 60 days can find an indication in placing a percutaneous gastrostomy. The advantage for the patient is a much better psychological tolerance compared with a naso-gastric tube. Also the incidence of mechanical complications of a PEG is much lower. In our experience from October '90 to July '92 we followed 34 patients with PEG, 22 males and 12 females, with mean age of 69 years (range 41-88). We used 9-French tube placed using the pull-method technique. All patients received antibiotic therapy for 5 days. About 12 hours after PEG placement all patients began using the gastrostomy, initially with the administration of electrolyte solutions and later with enteral polymeric formulas. The constant increase led all patients to a 1500 non protein calories daily intake in 3-4 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357883 TI - [Intensive care management of diffuse septic peritonitis]. AB - The function of the peritoneum in severe abdominal sepsis involves specific properties and defence mechanisms: large surface, efficient barrier, continuous mobility, capacity of migration, multiplication, secretion and absorption. The development of peritonitis supposes an initial lesion of the peritoneal surface by septic or biochemical mechanism. Peritoneal response consists of: septation of the abdominal wall, adhesion of the omentum to damaged surfaces or visceral perforation, massive stepping up of cellular and humoral defence mechanism. In our opinion therapeutic procedures consist of: early surgical approach and management of the patient in an intensive care unit. The aim of the medical therapy is: treatment of multiple organ failure (anti-infectious therapy, hemodynamic support, treatment of respiratory and renal failure, support of the hepatic failure and balancing of metabolic changes) and prevention of the most common complications: bleeding from upper gastrointestinal tract and thromboembolic risks. PMID- 8357885 TI - [Major clinical complications of hepatic cysts and angiomas. Report of 8 cases]. AB - The detection of hepatic cysts and hemangiomas has become relatively frequent after the diffusion of US imaging, but rarely they cause major clinical problems. We report our experience with 8 cases (4 cysts and 4 hemangiomas) which caused either signs and symptoms simulating a hepatic disease or compression on vascular structures with systemic consequences. PMID- 8357884 TI - [Purified human IgG administration, after chemotherapy, to patients with colorectal carcinoma]. AB - The authors, in the present study try to test the prophylactic effect of human IgG on surgical patients affected by colorectal cancer and undergoing chemotherapy in order to prevent microbial infections, supporting immunological host defences. PMID- 8357886 TI - [Alcohol-dependent mast cell activation in ulcer]. AB - Numerous studies have shown that alcohol causes both acute and chronic damage to gastroduodenal mucosa. The methods of damage differ however, and experimental studies in animals have shown that the degranulation of mast cells in gastric mucosa causes acute hemorrhagic lesions after the consumption of alcohol. It is not known whether this mechanism also operates in man. The aim of the present study was therefore to evaluate whether there is a correlation between mast-cell activation, determined by assaying tryptase levels in gastric mucosa, and the consumption of alcohol in patients with ulcerative diseases. Thirty-one patients with cicatrized ulcerative lesions (13 gastric ulcers, 18 duodenal ulcers) were included in the study. Biopsies at the level of the gastric fundus and antrum and the duodenal bulb were performed in all patients to determine tryptase levels. Biopsy material was frozen and subsequently homogenized; the enzyme was assayed in the supernatant using a radioimmunometric method. The mean daily alcohol consumption was calculated in clinical terms for each patient over the past 5 years and patients were subdivided into non-drinkers and moderate (< 60 g alcohol/day) and excessive (> 60 g alcohol/day) drinkers. It was found that tryptase concentrations were higher in the fundus compared to the gastric antrum and duodenal bulb, irrespective of alcohol consumption both in patients with gastric ulcer and duodenal ulcer. The importance of mast cells in provoking alcohol-dependent damage was studied at a gastric level. Alcohol leads to their degranulation and therefore contributes to the formation of gastric lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357887 TI - Factors associated with heroin users' AIDS risk-taking behaviours. AB - A survey was undertaken in Sydney in 1989 to identify factors associated with behaviour involving risk for human immunodeficiency virus infection. Self-report data on needle-sharing and sexual practices were collected from 91 heroin users entering a residential, drug-free detoxification unit. Data were analysed using polytomous and ordinal logistic regressions. Heroin-dependent subjects who also had a current alcohol problem were significantly more likely than others to report high risk needle-sharing behaviour. Subjects with more than one sexual partner in the last three months were significantly more likely to use condoms while those with a current benzodiazepine problem were significantly less likely to use condoms. Qualitative data suggest that high risk needle-sharing behaviour most often occurred around the time of relapse to injecting drug use and among homeless drug users occupying derelict buildings in inner-city suburbs. PMID- 8357888 TI - Medication use and its correlates among the elderly. AB - Medication use and its correlates were examined in a randomly selected sample of 178 urban-dwelling elderly people: 89 per cent were currently using medication and 44 per cent were using four or more medications concurrently. Forty percent were using at least one nonprescription medication, usually in combination with prescription medication. The treatment of hypertension was the most commonly given reason for medication use. Respondents demonstrated good knowledge of their medication and how to take it, and good compliance with prescribing instructions. Multiple medication use was associated with advanced age, living in supervised accommodation, and a range of measures indicative of reduced wellbeing. There was no association between cognitive functioning and multiple medication use. These findings suggest that stereotypical images of older people as being poor compliers and having little knowledge about their medication should be treated with caution. However, the extensive use of medication and of multiple medications and concerns about the appropriateness of use of some classes of medication highlight the need for more detailed study of medication use among the elderly. PMID- 8357889 TI - Generalism and specialism in public health. PMID- 8357890 TI - The benefits of exercise in postmenopausal women. AB - Physical exercise is commonly promoted as a panacea. However many of the claimed benefits, in particular any positive effects on bone density, have not been scientifically proved. We assessed the effects of a twice-weekly aerobic weight bearing exercise program on bone density in postmenopausal women. We tested bone density at the spine and hip in 19 exercisers with a mean age of 66.4 years (SEM +/- 1.2) before and after a two-year exercise program, and in 11 controls, mean age 65.4 years (SEM +/- 1.5). We also assessed risk factors for cardiovascular disease and tested wellbeing and cognitive function. The mean percentage change in lumbar bone mineral density was -0.8 in exercisers and -3.8 in controls (difference 3.0 per cent; 95 per cent confidence interval (CI) 0.3 to 5.7 per cent; P = 0.031). The mean percentage change in trochanteric bone mineral concentration was +9.6 in exercisers and -4.4 in controls (difference 14.0 per cent; CI 4.6 to 23.5; P = 0.0049). The exercisers also had significantly higher wellbeing and diastolic blood pressure. This study adds strong evidence that twice-weekly weight-bearing aerobic exercise has a protective effect on bone density in postmenopausal women as well as being associated with other measurable benefits. PMID- 8357891 TI - Testing for HIV infection among heterosexual, bisexual and gay men. AB - This paper answers the questions: who is and is not tested for human immunodeficiency virus (HIV) antibodies, why, where are they tested, and what do they find difficult about the testing process? The data came from two samples of sexually active heterosexual, bisexual and gay men in Perth (N = 545). Bisexual and gay men were much more likely to be tested than heterosexual men, although the commonest reason for testing for all three groups was risky sex. The three groups differed on reasons for not having the HIV antibody test: heterosexual men most commonly claimed that they were not at risk; bisexual men explained that they had been meaning to go but kept putting it off; and gay men primarily feared a positive test result and lacked trust in the confidential treatment of results. Gay men were more likely to trust their regular doctors than were heterosexual and bisexual men who had more trust in state health clinics. Waiting for test results was the most difficult part of the testing process for all respondents. Few respondents agreed that employers and the police should be notified by a doctor of an antibody-positive test result; nearly all agreed that those who had contracted HIV should be notified; notification of surgeons received moderate support. Knowing one's HIV infection status appears to be strongly associated with safer sex practices, and therefore the HIV antibody test could be promoted as part of a preventive health care program. PMID- 8357892 TI - Sexual practices, sexually transmitted diseases and other risk factors for HIV among injecting drug users. AB - Data were collected from 814 clients attending anonymously for counselling before tests for human immunodeficiency virus (HIV) infection at the Burnett Clinic in Auckland. Just over 10 per cent of clients (n = 83) reported ever having injected drugs. This group was matched according to age, gender, ethnicity and sexual orientation with an equal sized control group drawn from clients who had not injected drugs. The groups were compared in terms of their sexual practices, sexual partnerships, other drug use, current and past health status and their perception of HIV risk. The injecting drug users reported more sex partners than the nonusers, they were less likely to be in a relationship and they were less likely to be monogamous. Vaginal and oral sex were the most common practices in both groups but anal sex was more common among users than the nonusers. Regular condom use was reported by less than a quarter of each group. The health status of drug users was generally poorer than that of the nonusers. They reported greater use of alcohol and other drugs, more mental health problems, and more symptoms of ill health. They also had experienced more sexually-transmitted diseases. Only 1 per cent of users and 2 per cent of nonusers tested positively for HIV, although users saw themselves and their partners as at greater risk of HIV infection than the nonusers. PMID- 8357893 TI - A holosphere of healthy and sustainable communities. AB - Public health practice is in a transitory state, expanding considerably beyond medical and behavioural models of health and disease to encompass physical and social environmental health determinants. A new public health practice is emerging, apparent in initiatives like the international healthy cities/communities projects. This new public health practice must integrate the challenge of sustainable development, as defined by the 1987 World Commission on Environment and Development. The holosphere framework locates health as its central metaphor, and defines six interacting environmental spheres: a viable natural environment, a sustainable economic environment, a sufficient economy, an equitable social environment, a convivial community, and a livable built environment. There are five functional roles for local government: policy, legislation, education, partnerships and advocacy. Representative actions from each of the six environmental spheres of the holosphere framework are identified and discussed, using the five functional roles of local government. There is a need for new intersectoral forums to act upon the knowledge generated by integrative models such as the holosphere. Canadian Round Tables on Environment and Economy are encouraging examples of such intersectoralism. PMID- 8357894 TI - Cost-effectiveness of mammographic screening in Australia. AB - The purpose of this research was to estimate the cost-effectiveness of mammographic screening to supplement the results of the National Evaluation of Breast Cancer Screening which identified the mortality benefit as the most sensitive parameter. This appraisal used a different computer model, MISCAN, which models the effects of introducing a national screening program into a previously unscreened population, rather than basing estimates on the assumption of a fully established program. For the 40 to 49 age group a mortality reduction of 8 per cent was assumed, rather than the 30 per cent estimate utilised in the National Evaluation. The revised estimate is based on the two Swedish trials (Malmo and WE). New estimates for treatment costs were also incorporated into the MISCAN model. The cost-effectiveness of the policy recommended in the National Evaluation Report, $11,000 per life year saved with two-yearly screening of women over 40, is estimated by the MISCAN model to be $20,300. These differences arise partly from the difference in mortality effects for the 40 to 49 age group, but also from differences inherent in the steady-state and dynamic population approaches to modelling premature deaths averted. The MISCAN results confirm that screening for women over 50 is more cost-effective than screening women under 50. Screening all women aged 50 to 69 every two to three years is reasonable value for money. For women aged 40 to 49 the mortality benefit and cost-effectiveness is less clear, and it would be prudent to allow screening in this group until further evidence is available. PMID- 8357895 TI - Information-seeking behaviour and sources of health information: associations with risk factor status in an analysis of three Queensland electorates. AB - Making a special effort to gain health information has been associated with healthy behaviour. This paper identifies the information-seeking dimension and the sources of information people use and examines whether there is an association between these and individual health status. In November 1989 a randomly selected sample of 2134 adults in the electorates of Maryborough, Toowoomba and Port Curtis (Gladstone) completed a self-administered questionnaire which aimed to measure health-related knowledge, attitudes and behaviour. Factor analysis identified clusters of items representing different dimensions of risky health behaviour as well as different perceived barriers to seeking preventive health care. Multiple regression analysis was then used to determine sociodemographic, attitudinal and behavioural variables related to a tendency not to seek health information and to be at risk for preventable diseases. The findings have implications for the development of future health promotion programs in provincial Australian cities. Both age and sex were significant in predicting where people obtain information on health. Women were more likely than men to seek health information and their sources of information reflected this proactive attitude to health. While there was no significant difference between the perceived health status of males and females, reported behavioural risk factors were much more prevalent in males. Most respondents had consulted a general practitioner in the previous twelve months and stated that they would change their behaviour on the advice of a medical practitioner. However, few nominated medical practitioners as their main source of health information. PMID- 8357896 TI - Social controls, harm minimisation and interactive outreach: the public health implications of an ethnography of drug use. AB - This is a report on ethnographic research with the members of a social network of young, recreational, illicit drug users in Perth, Western Australia, with whom I maintained close social interaction for over twelve months. Following the work of Zinberg, the article outlines some of the main social controls employed by these young drug users to reduce drug-related harm. These social controls are of two types: sanctions (the rules prescribing certain behaviours and proscribing others) and rituals (the stylised behaviour surrounding the use of drugs). There exists an ideology of harm minimisation amongst drug users which may provide the basis for innovative programs. The implications of these findings are discussed with reference to one particular public health strategy, outreach, and the possibility of a more active, reciprocal and beneficial engagement between drug users and researchers, health educators and policy makers is suggested. PMID- 8357897 TI - Health and housing--seasonality in New Zealand mortality. AB - The common belief that New Zealand's climate is mild appears to be supported by the statistics of deaths directly attributable to cold. However an initial analysis of seasonality of mortality using the modified Edwards method suggests New Zealand has a greater seasonality of mortality than the more extreme climates of the United Kingdom, the United States, Australia, Japan or Sweden. Examination of New Zealand monthly mortality from 1976 to 1986 suggests this is driven by the seasonality of mortality of those aged 65 and over. Three surveys of temperatures within New Zealand homes have suggested that few are fully maintained in the 18 degrees C to 24 degrees C comfort range. Mean temperatures close to or below 16 degrees C were found in two of these surveys. Further research is suggested to examine the links between health and housing thermal performance. This research should combine both health and building science knowledge and techniques. PMID- 8357898 TI - Heart disease risk factors in the Vietnamese community of southwestern Sydney. AB - Despite low mortality from heart disease in the New South Wales Vietnamese community, the prevalence of risk factors for heart disease has been increasing. This study sought to identify the prevalence of heart disease risk factors in the Vietnamese community in southwestern Sydney. In 1991, 389 randomly selected Vietnamese-born residents of southwestern Sydney (79.2 per cent response rate) were interviewed by telephone about their risk status. Sixty-one per cent of this sample agreed to a second interview in their homes where physical measurements were taken. Smoking prevalence was high in males (53 per cent), whereas raised blood pressure (5.1 per cent), high blood cholesterol (21.1 per cent) and overweight (14.0 per cent) had a low prevalence compared to National Heart Foundation data for the general population. Interventions targeting males about smoking should be a health promotion priority, and the maintenance of the traditional Vietnamese diet should be encouraged. PMID- 8357899 TI - Bulk-billing of general practitioner services: the evidence. PMID- 8357900 TI - Bulk-billing of Medicare: more about the evidence. PMID- 8357901 TI - Prevalence of hearing loss. PMID- 8357902 TI - General practice smoking cessation. PMID- 8357903 TI - Cervical cancer screening by women's health nurses. PMID- 8357904 TI - Evaluating petrol-sniffing prevention programs. PMID- 8357905 TI - Clinical pathology reference ranges of laboratory animals. Working Group II, Nonclinical Safety Evaluation Subcommittee of the Japan Pharmaceutical Manufacturers Association. AB - We analyzed historical control data of clinical pathology testings provided by sixty-seven member companies of the Japan Pharmaceutical Manufacturers Association covering study populations of approximately 7,000 rats/sex, 5,000 dogs/sex, and 700 monkeys/sex. This paper assesses the relationship between conditions of sample collection, methods of measurement, etc. and potential factors contributing to variations in reference data, based on weighted means and standard deviations thereof derived from data for rats, dogs and monkeys for those parameters measured using methods most common to the participating facilities. Parameters included erythrocyte count (RBC), hematocrit (Ht), hemoglobin concentration(Hb), reticulocyte count (Rt), platelet count, total leukocyte count (WBC), differential leukocyte count (%WBC), coagulation time (activated partial thromboplastin time: APTT, prothrombin time: PT), and serum/plasma levels of GOT, GPT, ALP, LDH, glucose, cholesterol, triglycerides (TG), total protein, albumin, urea nitrogen (UN), creatinine, sodium (Na), potassium (K), calcium (Ca), chloride (Cl), inorganic phosphorus (Ip), and CPK. Analyses of the data revealed species differences in RBC, Ht, Rt, platelet count, WBC, %WBC, ALP, LDH, glucose, cholesterol, TG, total protein, UN, creatinine, Ca, Ip, and CPK. There were strain differences in rats in platelet count, WBC, GOT, ALP, UN, creatinine, and CPK. Sex differences were noted for Hb, Ht, WBC, ALP, glucose, cholesterol, TG, total protein, A/G ratio, UN, and Ip. Age differences were observed with RBC, Hb, Ht, Rt, %WBC, GOT, GPT, ALP, LDH, cholesterol, TG total protein, Ip, and CPK. APTT, PT, ALP, glucose, TG and UN were found to be subject to the influence of fasting/feeding. In rats, Ht, WBC, CPK and K showed differences by the site of bleeding. Observed values for LDH and CPK varied with specimen type, plasma or serum; serum assay values showed greater variation than plasma values. PMID- 8357906 TI - Comparative study of Trichuris trichiura from non-human primates and from man, and their difference with T. suis. AB - Whipworms from the macaque and baboon were studied by light and scanning electron microscopy. They were identified as Trichuris trichiura, though a slight variation was observed in the length of spicule as compared with the whipworms collected from man. Moreover, a row of small knob-like structures was observed at the base of the pericloacal papillae of T. trichiura from the monkey by scanning electron microscopy. T. trichiura from non-human primates and man has been reported to be morphologically indistinguishable from T. suis. However, this study showed that males of T. trichiura from both the monkey and man can be differentiated from T. suis from the pig on the basis of the presence of a pair of pericloacal papillae and a cluster of small papillae near the caudal end in the former, which is totally absent in the latter. PMID- 8357907 TI - Visual dysfunction in aged Fischer 344 rats. AB - To investigate age-related changes in visual function in rats, male and female Fischer 344 (F344) rats at 30 months of age were examined electrophysiologically and histopathologically. The selection rate for the dark area in a T-shaped test box was 80% in aged rats, and the ability of light-dark discrimination was definitely depressed. Electroretinogram (ERG) was non-recordable in 25 out of the 28 eye balls examined, and amplitudes of the ERG a- and b-waves were markedly depressed in the remaining three eye balls. Histopathologic examination of the retina revealed marked atrophy of photoreceptor cells on the outer nuclear and photoreceptor layers; the change was less extensive in the retina of eye balls in which ERG was recordable. Immunohistochemically, increased reactivity to anti glial fibrillary acid protein serum was observed in the retina of the aged animals. These results evidenced that the number of photoreceptor cells is decreased in age F344 rats, resulting in the reduced reactivity to light and the depressed light-dark discrimination. PMID- 8357909 TI - Constrictive effect of thyroxine on the ductus arteriosus in fetal rats. AB - This work was conducted to know whether thyroxine (T4) when injected into fetal rats would induce a constriction of the ductus arteriosus (DA). In Experiment 1, fetal rats on day 20 of gestation were given a subcutaneous injection of 1 or 10 micrograms T4 through the maternal uterine wall, and were autopsied 3 or 6 hr later. Similarly, in Experiment 2, the mother rats were given an injection of hydrocortisone (10 mg/kg) just after fetal T4 injections. In either series of experiments, uninjected littermates served as controls. According to the whole body freezing and shaving method, the DA was exposed and calibrated under a dissecting microscope. In Experiment 1, the DAs of the T4-injected fetuses, 3 hr later, were significantly smaller in caliber than those of their controls, but recovered 6 hr later. In Experiment 2 with fetal T4 injection followed by maternal hydrocortisone injection, the DAs of the T4-injected fetuses were further smaller in caliber than those of their controls which were clearly shrunken as compared with those of controls in Experiment 1. These results indicate that T4 exerts a constrictive effect on the DA, an effect which is strengthened in the presence of hydrocortisone. PMID- 8357908 TI - Developmental changes in paramesonephric and mesonephric ducts and the external genitalia in swine fetuses during sexual differentiation. AB - The paramesonephric (Mullerian) duct was first observed in the vicinity of the mesonephric (Wolffian) duct in 30-day-old swine fetuses of both sexes at the level close to the gonad. The paramesonephric duct extended caudally in parallel with the mesonephric duct on day 35 of gestation. By day 40 the paramesonephric duct reached the urogenital sinus. At this stage, the paramesonephric duct began to degenerate in the male, while it continued to develop in the female. This suggests that an anti-Mullerian duct hormone (AMH) is produced before day 40 of gestation. By day 45 of gestation, the mesonephric duct began to decrease in diameter and was accompanied with the involution of the mesonephros in both sexes. By day 60, the male and female mesonephric ducts reduced in their diameter by 70%. Thereafter, the female mesonephric ducts disappeared, while the male ducts developed again. The sex differences was first observed on day 35 in the differentiation of the external genitalia when a small circular urogenital orifice and the anogenital raphe appeared at the sites caudal to the genital tubercle in the male. Such structures were not present in the female. These results suggest that the fetal pig testis is activated to secrete androgen before day 35 of gestation. PMID- 8357910 TI - Inhibitory effect of fenthion and diazinon on the contraction of rat aorta, and its contribution to lethality. AB - Fenthion and diazinon, P = S type organothiophosphates which are precursors of cholinesterase inhibitors, cause remarkable atropine-insensitive hypotension in rats when administered intravenously in lethal doses. We investigated their effects on isolated rat aorta and atria to reveal the site of action. Fenthion and diazinon inhibited both types of contractions induced by high K+ solution and norepinephrine in aortic preparations from which the endothelium was removed. IC50 values (under [Ca2+] = 1.5 mM) were 2 x 10(-5) M and 7 x 10(-5) M, respectively. However, the atrial preparations were relatively resistant, since fenthion showed no effect up to 10(-3) M and diazinon at 10(-4) M exhibited a slight inhibition which was antagonized by atropine. The hypotensive effect of fenthion or diazinon was therefore attributable to the direct inhibiting action on the arterial muscle tone, which may be independent of the activation of muscarinic receptors. The results suggested that fenthion and diazinon affect movement and/or utilization of calcium in the aortic muscle cells, since an increase in the calcium concentration in the bathing solution antagonized their inhibitory effect. PMID- 8357911 TI - DNA sequence of type 1 fimbrin, Fpul1, gene from a chicken pathogenic Escherichia coli serotype O78. AB - The gene encoding type 1 fimbriae of chicken pathogenic Escherichia coli serotype O78 (designated Fpul1) was cloned and the genetic region encoding fimbrial subunit was sequenced. The nucleotide sequence and its deduced amino acid sequence demonstrated that the Fpul1 was a novel variation among E. coli type 1 fimbriae and showed an extensive homology to previously reported Klebsiella pneumoniae type 1 fimbriae. The E. coli K-12 strains carrying the Fpul1 genes did not show the acid-induced autoagglutination, suggesting that the Fpul1 was genetically distinct from the acid-induced autoagglutination. PMID- 8357912 TI - Purification of toxic saponins from Narthecium asiaticum Maxim. AB - Toxic substances in Narthecium asiaticum Maxim. were isolated and purified, monitoring the oral toxicity in guinea pigs. The crude extract prepared from the methanolic extract of the plant contained 2 major saponins (C8 and C9), and 7 corresponding saponins (C1-7) on TLC. The crude extract was fractionated by a conventional method for saponin preparation. The 1-butanol fraction was rich in C8 and C9, and showed oral toxicity. C8 and C9 were isolated by fractional precipitation and silica gel column chromatography. On the basis of C-13 and H-1 nuclear magnetic resonance (NMR) spectral data, and acid and enzymatic hydrolysis of C9, C9 was confirmed to be a mixture of two furostanol saponins (C9a, C9b); a branched trisaccharide composed of galactose, glucose, and arabinose, was linked at 3 beta-C, and glucose at 26-C of sarsasapogenin and smilagenin. C8 was considered to be a furostanol saponin containing xylose instead of arabinose in the structure of C9. Oral administration of C8 and C9 caused diarrhea, proteinuria, hematuria and death in guinea pigs. PMID- 8357913 TI - Preliminary results of short-term combination immunosuppressions of mizoribine, azathioprine, and prednisolone with pretreatment to canine kidney transplantation. AB - Serial combinations of immunosuppressive drugs (mizoribine: Mi, azathioprine: Az, and prednisolone: Pr) were administered for renal heterotopic allotransplantation in 50 mixed-breed dogs and 4 beagle dogs. The dogs were randomly divided in 5 groups depending upon immunosuppressive protocols. All immunosuppressive protocols were started at 5 days prior to transplantation and discontinued on the eighth day after transplantation. The mean survival time for the allograft recipients in the group receiving Az and Pr [Az (2.5) & Pr group; Az dosage, 2.5 mg/kg once a day with Pr] was 16.2 +/- 2.4 days and in the group receiving Az, Mi, and Pr (Mi & Az & Pr group; Mi dosage, 5.0 mg/kg once a day with Az and Pr), it was 14.0 +/- 2.6 days. These results were significantly longer than the control group (mean survival time, 8.7 +/- 2.4 days; P < 0.01). There was no statistical difference in survival time between these two groups. Groups with combinations of Az and Pr had significant elevations of hepatic enzymes (ALT and ALP) during the 7 days of immunosuppressive treatment after kidney transplantation. The Mi & Az & Pr group had lower elevations of hepatic enzymes than groups with combinations of Az and Pr. The combination immunosuppression of Mi, Az, and Pr with pre-treatment for canine, kidney transplantation revealed relatively fewer side-effects for the liver and longer survival-time. PMID- 8357914 TI - Species- and organ-specificity and expression of 105 kD liver cell membrane glycoprotein antigen during rat development. AB - Species- and organ-specificity of a rat liver cell antigen recognized by a monoclonal antibody (MoAb) from a hybridoma clone RM-1 was investigated immunohistologically and immunoelectronmicroscopically. In rats, the MoAb reacted specifically with liver cell membrane, but not with other organs tested, including the brain, thymus, heart, lung, stomach, spleen, kidney, small and large intestines, testis and muscle. Furthermore, it was found that liver from the human, monkey, mouse, rabbit, guinea pig, dog, cat, cattle and chicken showed no specific reaction with this MoAb. The results indicated that the antigen was organ- and species-specific and designated as rat liver cell-specific membranous antigen (RLSA). RLSA was expressed scarcely along cell junctions of immature hepatocytes at the 19th day of pregnancy. This increased gradually, and was expressed along all surface membranes after birth. PMID- 8357915 TI - The bronchial tree, lobular division and blood vessels of the masked palm civet (Paguma larvata) lung. AB - The right lung of the masked palm civet (Paguma larvata) consists of the cranial, middle, caudal and accessory lobes. The left lung has no cranial and accessory lobes and has a bilobed middle and caudal lobes. On either side, there are four bronchiole systems, i.e. dorsal, lateral, ventral and medial. The right cranial lobe is formed by the first bronchiole of the dorsal bronchiole system. However, this bronchiole arises from the right lateral side of the trachea, the so-called tracheal bronchus (bronchiole). The right middle lobe is formed by the first bronchiole of the lateral bronchiole system, and the right accessory lobe is formed by the first bronchiole of the ventral bronchiole system. The remaining bronchioles of the dorsal, lateral and ventral bronchiole systems and a bronchiole of the medial bronchiole system constitute the right caudal lobe. In the left lung, the left middle lobe is formed by the first bronchiole of the lateral bronchiole system. This bronchiole divides into two branches, each of which forms a lobule. The remaining bronchioles constitute the left caudal lobe as in the right lung. The branches of pulmonary arteries mostly run along the dorsal or lateral side of bronchioles. The pulmonary veins run the ventral or medial side of bronchioles and between the bronchioles. PMID- 8357916 TI - The bronchial tree and lobular division of the horse lung. AB - The lungs of five horses were examined. At present, in veterinary anatomy, the horse lung is divided into the cranial and caudal lobes by the cardiac notch on either side. In addition to these lobes, in the right lung, the accessory lobe is present. However, from the viewpoint of the bronchial ramifications, the horse lung can be divided into the cranial, middle, caudal and accessory lobes bilaterally. The horse lung has four bronchiole systems on either side, dorsal, lateral, ventral and medial. The cranial lobe is formed by the first bronchiole of the dorsal bronchiole system. The middle lobe is formed by the first bronchiole of the lateral bronchiole system. The accessory lobe is formed by the first bronchiole of the ventral bronchiole system. The remaining bronchioles of the dorsal, lateral and ventral bronchiole systems and all bronchioles of the medial bronchiole system constitute the caudal lobe. These features were compared with those of the lungs of other domestic animals. PMID- 8357917 TI - Pharmacokinetics and tolerability of chloramphenicol in budgerigars (Melopsittacus undulatus). AB - Pharmacokinetics and tolerability of chloramphenicol (CP) were evaluated in budgerigars. Following intramuscular administration of CP at 100 and 200 mg/kg of body weight, serum peak concentrations of 35.3 and 90.7 micrograms/ml, respectively, were obtained 0.25 hr following injection, and these values declined with a terminal half-life of 2.5 and 2.7 hr, respectively. Based on these results, an intramuscular dosage regimen of 100 mg/kg of CP 3 times a day or of 200 mg/kg twice daily was recommended as effective against many of the common bacterial infections in budgerigars. Red blood cell count, packed cell volume, hemoglobin, total plasma protein, serum AST, ALT, LDH and CK values were determined after intramuscular injection of either CP or physiological saline 2 or 3 times a day for 5 days. The birds were weighed before and after treatment. Tissue samples from various organs were examined histologically. The most prominent adverse effect was muscular damage at the injection site. A dosage regimen of 200 mg/kg twice daily for 5 days was considered to be safe. PMID- 8357918 TI - The bronchial tree, lobular division and blood vessels of the Japanese deer (Cervus nippon) lung. AB - The bronchial tree, lobular division and blood vessels of the lungs were examined in three Japanese deer (Cervus nippon). The dorsal, lateral, ventral and medial bronchiole systems arose from the dorsal, lateral, ventral and medial sides of both bronchi, respectively. Furthermore, one bronchiole arose from the right side of the trachea, namely the tracheal bronchus (bronchiole). This bronchiole formed the right cranial lobe. The right middle lobe was formed by the first bronchiole of the lateral bronchiole system. The right accessory lobe was formed by the first bronchiole of the ventral bronchiole system. The remaining bronchioles of the four bronchiole systems constituted the right caudal lobe. In the left lung, the cranial and accessory lobes were absent. The left middle lobe was formed by the first bronchiole of the lateral bronchiole system. This bronchiole was well developed and formed a bilobed middle lobe. The remaining bronchioles constituted the left caudal lobe. The right lung consisted of the cranial, middle, caudal and accessory lobes. The left lung consisted of the middle and caudal lobes. The branches of the pulmonary arteries ran mostly along the dorsal or lateral side of the bronchioles. The pulmonary veins ran the ventral or medial side of the bronchiole, and between the bronchioles. PMID- 8357919 TI - A clinical trial of recombinant bovine interferon alpha 1 for the control of bovine respiratory disease in calves. AB - The effects of recombinant bovine interferon alpha 1 (rBoIFN alpha 1) on the incidence of bovine respiratory disease (BRD) were examined in 60 young male cattle. Each group of clinically healthy 30 male cattle was injected intramuscularly with either rBoIFN alpha 1 (5 mg/head) or physiological saline 5 times in 6 months. They were examined daily for the clinical symptoms of respiratory distress. The clinical signs of respiratory distress in rBoIFN alpha 1-treated cattle were significantly less severe than those of the placebo group. The incidence rate, relapse rate and mean sick days of respiratory disease in the rBoIFN alpha 1-treated group were 23%, 14% and 4.43 days, respectively, whereas those in the placebo group were 80%, 46% and 6.42 days, respectively. Furthermore, the mean increase of body weights in rBoIFN alpha 1-treated group and placebo group were 1.365 kg/day and 1.340 kg/day, respectively. These results suggest that rBoIFN alpha 1 has a potentially preventive effect on the incidence of BRD. PMID- 8357920 TI - An occurrence of equine transport pneumonia caused by mixed infection with Pasteurella caballi, Streptococcus suis and Streptococcus zooepidemicus. AB - An acute death occurred in a racehorse with pneumonia after long-distance transportation in December, 1990. Pasteurella caballi, Streptococcus suis and Streptococcus zooepidemicus were isolated from the lung at high rate. Specific antigens of these bacteria were also demonstrated immunohistologically in the pneumonic lesion. These findings indicated that the disease is equine transport pneumonia caused by a mixed infection of the three bacterial species. This is the first report on the isolation of P. caballi and S. suis from a racehorse in Japan. PMID- 8357921 TI - Spontaneous coronary arteriolosclerosis in broiler chickens. AB - Arteriolosclerotic changes were found in 202 out of 203 randomly collected heart specimens of broiler chickens. These chickens were reared in a poultry farm and killed at a poultry meat processing plant at 60 days of age with healthy appearance. Cellular intimal thickening due to a proliferation of smooth muscle cells of small arteries or arterioles were found mostly in the innermost layer of the left ventricle. Severity of the thickening varied from slight to severe. In 2 cases, myocardial necrotic changes were found in the proximity of severely affected small arteries and arterioles. PMID- 8357922 TI - A simple method of hybridohistochemistry for detection of renin mRNA in the mouse kidney. AB - Hybridohistochemistry was applied for the detection of renin mRNA in the mouse kidney with a digoxigenin-labeled probe, synthesized as the sense and antisense RNAs from Ren-1 cDNA in the presence of digoxigenin-dUTP. Renin mRNA was detected in the juxtaglomerular cells located in the vicinity of the glomerular vascular poles of the kidney using the digoxigenin-labeled antisense RNA as a probe. Using the sense RNA as a probe, no signal was detected anywhere. In neighboring serial sections, the same cells reacted immunohistochemically to rabbit anti-mouse submandibular gland renin serum as in hybridohistochemistry. As we used the probe labeled with digoxigenin as a non-radioisotopic marker, there was no need for special handling other than that in immunohistochemistry. It was concluded that the simple procedure given in the present study is useful for the detection of mRNA. PMID- 8357923 TI - Lymphoplasmacytic lymphoma in a stallion. AB - Lymphoplasmacytic lymphoma found in a 6-year-old Anglo-Arabian stallion was investigated histologically, immunohistochemically and ultrastructurally. The animal showed a large mediastinal mass and generalized lymph node involvement. The neoplastic cells were in various differentiation stages of small lymphocyte, centrocyte, centroblast, immunoblast and plasma cell. Some neoplastic cells showed positive cytoplasmic reactivity for mu and lambda chains. There were well developed rough endoplasmic reticulum (RER) and Golgi complexes in plasmacytoid cells, and slightly developed RER or a few long strands of RER in medium-sized to large lymphoid cells. These findings suggest that this neoplasm is of B-cell origin. PMID- 8357924 TI - Immunothermotherapy and related TNS induction in mice. AB - Induction of tumor necrosis factor in sera (TNS) as a multidisciplinary cancer therapy by the administration of a combination of 2-carboxyethylgermanium sesquioxide (Ge-132) and lipopolysaccharide (LPS) on Meth-A sarcoma-bearing mice was attempted. In addition to the above TNS induction therapy (TNS therapy) per se, the potential on the above parameters by employing a multidisciplinary cancer therapy (immunothermotherapy), in which TNS therapy was coupled with regional hyperthermia treatment, was investigated. This immunothermotherapy enhanced the antitumor effects produced by the above TNS therapy. PMID- 8357925 TI - Detection of Mycoplasma hyorhinis in porcine eustachitis. AB - Pathologic study of the ear was performed on 179 young swine, ranging in age from 1 day to 18.6 weeks. Histologically, eustachitis was the most common and its inflammatory reaction appeared to precede otitis. Immunohistochemically, Mycoplasma hyorhinis (Mhr) antigens were detected on the luminal surface of the auditory epithelia in 19 of 179 cases (10.6%). All the cases, positive for Mhr antigens, were associated with an acute eustachitis. Ultrastructural examination of two piglets confirmed these immunohistochemical data. The present results indicate that Mhr may be a primary cause of acute eustachitis in young swine. PMID- 8357926 TI - Placental and plasma cystine aminopeptidase in pregnant animals. AB - The placental and plasma cystine aminopeptidase (CAP) in pregnant animals was examined on stability after the treatment with L-methionine, ethylene diamine tetra-acetic acid (EDTA) and heat. Inhibitory effects of these treatments on enzyme activities were different among CAPs from the animal species, however, significant correlation in those effects between placental and plasma CAPs was observed. These results suggested that plasma CAP might reflect placental CAP and seemed to be available for estimating maternal gestational conditions. PMID- 8357927 TI - Protein kinase C and its endogenous substrate proteins in isolated cow liver parenchymal cells. AB - Protein kinase C activity was evaluated and its endogenous substrate proteins were explored in isolated cow liver parenchymal cells. Protein kinase C activity was detected in both cytosolic and total particulate fractions of the cells. At least four proteins in cytosolic and seven proteins in total particulate fractions were found to be substrates for protein kinase C. These results suggested that protein kinase C-catalyzed protein phosphorylation was involved in the regulation of functions of cow liver parenchymal cells. PMID- 8357928 TI - Heterotopic splenic tissue in the liver of a swine. AB - A heterotopic splenic tissue (HST) was observed in the diaphragmatic face of the right hepatic lobe of a 6-month-old, female mixed bred swine. Macroscopically, HST was a solitary, well-demarcated intrahepatic nodule, 1 x 0.5 x 0.5 cm in size. Other organs including original spleen showed no macropathological abnormalities. Histological findings of HST were essentially similar to those of the original spleen, receiving feeding blood vessels from hepatic portal vein. To our knowledge, the present case is the first report of HST in the liver not only of domestic animals but also of man. PMID- 8357929 TI - Biochemical polymorphisms in Long-Evans Cinnamon (LEC) inbred strain of rat. AB - Long-Evans Cinnamon (LEC) rat is an inbred strain of mutant rat which has been proposed to be an animal model for human Wilson's disease. In the present study, 28 genetic marker proteins were analyzed by electrophoresis in sublines of LEC inbred strain held separately by four facilities. As expected, the 27 markers were homozygous and identical in all of examined animals. We further found a novel variant of esterase-2 (ES-2) showing an intermediate mobility between profiles of ES-2A and ES-2C types. PMID- 8357930 TI - Five cases of cranial duplication in calf. AB - Five cases of cranial duplications in calves were morphologically reported. Each calf had a single body with duplicated heads that showed various degrees of fusion. The medial sides of individual heads were asymmetrically supplied by the branches of hemilateral common carotid or lingual artery. No marked differences in the development of the duplicated head in any of the calves were observed. Cleft palates were observed in all heads. The development and general structures of the organs in the head and neck regions appeared to depend on the degree of duplication of the cranial nerves. PMID- 8357931 TI - Induction of serum haptoglobin by administration of ethionine to cows. AB - In order to assess the association of cow serum haptoglobin with fatty liver, haptoglobin concentrations were evaluated by single radial immunodiffusion in sera from cows after administration of ethionine (an analogue of methionine). Haptoglobin concentrations were found to be increased in the sera of the ethionine-administered cows. This result suggests that the induction of haptoglobin is associated in the pathogenesis of fatty liver. PMID- 8357932 TI - Immunosuppression in dogs naturally infected with Babesia gibsoni. AB - We examined lymphoproliferative response to phytohemagglutinin and anti-parasite antibody level in dogs naturally infected with Babesia gibsoni. The dogs with subclinical B. gibsoni infection exhibited suppressed lymphocyte blastogenesis. Prominent depression of lymphocyte blastogenesis and anti-parasite antibody production was observed in dogs suffering from relapses of clinical B. gibsoni infection. PMID- 8357933 TI - Production of cytolethal distending toxin (CLDT) by Campylobacter fetus subsp. fetus isolated from calves. AB - Cytolethal distending toxin (CLDT) production by Campylobacter fetus subsp. fetus isolated from calves was examined using CHO cells. Twenty-five of the 26 strains tested were positive for CLDT with titer of ranging 1:8 to 1:2,048. CLDT positive strains were divided into low and high cytotoxin titer groups. Isolates from diarrhea cases tended to produce a significant amount of CLDT compared with isolates from liver. CLDT produced by C. fetus showed no effect on Y-1 cells and was heat-labile and trypsin-sensitive. PMID- 8357934 TI - Outbreaks of Salmonella Dublin infection among calves on a dairy farm applying Salmonella bacterins in Zambia. AB - In Zambia, a dairy farm keeping about 600 cows and self-contained calves had applied S. Dublin and S. Typhimurium bacterins to pregnant cows and calves in combination with all-in all-out pen system for rearing calves. Only relatively small scale outbreaks of S. Dublin infection occurred repeatedly in these years from 1989 to 1991 among fattening calves on the farm. The results obtained from the epizootiological study suggest that the preventive measures including the vaccination with Salmonella bacterins gave insufficient protection against S. Dublin infection to the calves, but they might have prevented large scale outbreak of the disease. This is the first report of the epizootiological study on outbreak of bovine S. Dublin infection on farm in Zambia. PMID- 8357935 TI - Hydranencephaly in newborn calves in Zambia. AB - Hydranencephaly without arthrogryposis was observed in three newborn Holstein Friesian calves, born during one week in a 400-cow dairy herd in Zambia. The affected calves were blind and exhibited nystagmus and depressed behavior. Akabane virus infection was suspected based on the pathological findings and etiological data, however, we could not determine the exact causative agent. PMID- 8357936 TI - Establishment of reference ranges for thyrotropin, triiodothyronine, thyroxine and free thyroxine in neonates, infants, children and adolescents. AB - Thyrotropin, triiodothyronine, thyroxine and free thyroxine were determined in the sera of 714 euthyreotic neonates, infants, children and adolescents (age range 5 days to 18 years), using the IMx from Abbott Laboratories. Thyrotropin, triiodothyronine and free thyroxine were determined with microparticle enzyme immunoassays (MEIA). Thyroxine was determined with a fluorescence polarization immunoassay (FPIA). The proband collective was divided into 9 age groups, and each age group into males and females. In accordance with the recommendations of the International Federation of Clinical Chemistry, the 95% scatter range was taken as the reference range. In the different age groups, the ranges of some hormones showed significant differences between males and females. When no significant difference existed between the sexes, the results for males and females were evaluated statistically as a single group. Only a few reference groups showed normal Gaussian distributions. Therefore, in addition to the 50th percentile, the 2.5th and 97.5th percentiles were also calculated for all reference groups. Minimal and maximal values were also determined. The U-test of Mann & Whitney was used to test for significant differences between individual reference groups, and groups showing no significant differences were combined. The corresponding references ranges were then calculated. PMID- 8357937 TI - Assay of antinuclear antibodies by ELISA using nuclei as antigen. AB - An enzyme-linked immunosorbent assay to detect antinuclear antibodies in the sera of patients with autoimmune diseases is described. Goat liver nuclei were immobilized on polystyrene plates and antinuclear antibodies were used to standardize the assay. The effects of variables, such as the nuclei concentration, conditions of nuclei storage, and the length of the incubation period were investigated on the assay. Prototype sera with known antibody specificity were used to evaluate the assay. The method described is highly sensitive, autoantibodies being detectable at serum dilutions of 1:1000 or higher. According to the intra- and inter-assay coefficient of variation, the results were highly reproducible. PMID- 8357938 TI - Determination of lipoprotein(a): evaluation of three methods. AB - Lipoprotein(a) (Lp(a)) is a strong independent risk factor for premature atherosclerosis. Structurally, Lp(a) closely resembles LDL. Its protein moiety contains apolipoprotein B-100 and apolipoprotein(a). We evaluated two commercial enzyme immunoassays (EIAs) and an immunoradiometric assay (IRMA) for Lp(a). The three assays differed in their design and they used different antibodies. In the immunoradiometric assay, two different monoclonal antibodies were used. In the first EIA, monoclonal anti-apolipoprotein(a) was bound to the solid phase and Lp(a) was detected with polyclonal anti-apolipoprotein B (Lp(a):B-EIA). In the second EIA, polyclonal anti-apolipoprotein(a) was used as capturing antibody and as detecting antibody (apo(a)-EIA). Ninety three plasma samples were assayed for Lp(a) with the three methods. The best correlation was obtained between the IRMA and the Lp(a):B-EIA (r = 0.971). Correlations between the apo(a)-EIA on the one hand and the IRMA or the Lp(a):B-EIA on the other hand were 0.889 and 0.836, respectively. The methods significantly differed in their calibration. This resulted in different mean Lp(a) concentrations. When tested against purified Lp(a), the apo(a)-EIA appeared accurately calibrated, whereas the IRMA and the Lp(a):B-EIA overestimated Lp(a) by approximately twofold. In the Lp(a):B-EIA, the detecting antibody is directed against apolipoprotein B. The Lp(a):B-EIA is, therefore, not affected by apolipoprotein(a) size polymorphism. This allows expression of the concentration of Lp(a):B complexes on a molar basis. In contrast, the polyclonal antibody-based apo(a)-EIA measures the concentration of apolipoprotein(a) antigen, and may, therefore, be susceptible to inter- and intra individual polydispersity of apolipoprotein(a) and Lp(a) particles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357940 TI - Self-organizing neural networks as a means of cluster analysis in clinical chemistry. AB - Connectionist systems (often termed "neural networks") are an alternative way to solve data processing tasks. They differ radically from conventional "von Neumann" computing devices. Recent work on neural networks in clinical chemistry was done using supervised learning schemes, resulting in models which resemble classical discriminant analysis. The aim of the present study is to make clinical chemists familiar with basic concepts of self-organizing neural networks employing unsupervised learning schemes. Using a benchmark data set on the composition of milk from 22 different mammals, it is demonstrated that self organizing neural networks are capable of performing tasks similar to classical cluster analysis and principal component analysis. Self-organizing neural networks could be envisaged to provide an alternative way for reducing the dimensionality of complex multivariate data sets, thus producing easily comprehensible low-dimensional "maps" of essential features. PMID- 8357939 TI - A high-performance liquid chromatographic method for the determination of hypoxanthine, xanthine, uric acid and allantoin in serum. AB - A method was developed for the simultaneous determination of hypoxanthine, xanthine, uric acid and allantoin based on isocratic reversed-phase chromatography. This HPLC-method additionally allows the direct determination with UV-detection of inosine-5'-phosphate, uridine, thymine, orotic acid, allopurinol and oxipurinol, besides hypoxanthine, xanthine and uric acid in the same chromatographic run. Allantoin elutes in this system near the void volume and a fraction is collected covering the retention time range for this substance. After hydrolysis allantoin is converted to glyoxylate-2,4-dinitrophenylhydrazone, rechromatographed and detected at 360 nm. The coefficient of variation for this method does not exceed 5.0% for a serum concentration of 0.3 mumol/l hypoxanthine and is not greater than 5.3% for a xanthine concentration of 0.3 mumol/l serum. Recoveries were 90-110% for both hypoxanthine and xanthine. The determination of uric acid had an imprecision and inaccuracy not exceeding 1.45% in the concentration range of 103-568 mumol/l. Due to the more complex procedure required for the determination of allantoin, the coefficient of variation between days was 13.6% for a sample containing 0.8 mumol/l allantoin and the recoveries for this analyte were in the range of 86-93%. Reference ranges (mean +/- SD) determined on 171 serum samples from healthy adults were 12.7 +/- 6.6 mumol/l for hypoxanthine, 3.3 +/- 1.4 mumol/l for xanthine, and 15.7 +/- 7.9 mumol/l for allantoin. No significant age or sex dependence was observed. Uric acid concentrations were 320 +/- 55 mumol/l serum for men and 206 +/- 55 mumol/l for women. PMID- 8357941 TI - The use of liquid chromatography-mass spectrometry for the identification and quantification of urinary iminodipeptides in prolidase deficiency. AB - It has been reported that the urine of patients with prolidase deficiency contains various iminodipeptides with a carboxyl-terminal proline (hydroxyproline). These iminodipeptides have hitherto been detected indirectly by acid hydrolysis or enzymatic digestion, followed by amino acid analysis. In the present study, it was shown that X-Pro could be distinguished from Pro-X when the iminodipeptides were analysed directly by liquid chromatography coupled with atmospheric pressure ionization mass spectrometry (LC/API-MS), with scanning of the protonated molecule ions ([M+H]+). The same procedure also successfully quantified urinary iminodipeptides from patients with prolidase deficiency. A quantitative investigation of two siblings with prolidase deficiency revealed that the patient with severe clinical symptoms excreted more iminodipeptides than the other who did not have serious symptoms. LC/API-MS also revealed iminodipeptides (Gly-Hyp and Pro-Hyp) in the urine of the mother of the patients and in normal volunteers. Patients excreted much more Pro-Hyp than normal volunteers, whereas no quantitative differences were found between the mother and controls. In patients, the excretion of large quantities of X-Pro is due to their very low prolidase activity towards this type of substrate. In the erythrocytes of patients, prolidase activity towards X-Hyp was extremely low; even in the mother and normal volunteers, it was remarkably low in comparison with the activity against X-Pro. PMID- 8357943 TI - Development and evaluation of a reagent carrier with a new reaction sequence for the determination of creatinine in blood, plasma, serum and urine. AB - After a short outline of the history of creatinine determination methods we describe the development of a dry-reagent-carrier system for the reflometric determination of the creatinine concentration in blood, plasma, serum and urine (Reflotron Creatinine (new)). The method is based on a sequence of enzymatically catalyzed reactions producing H2O2, but which in contrast to the previously used procedure do not lead to the formation of creatine as an intermediate. Hence, pretreatment of sample material to eliminate endogenous creatine is no longer necessary. In the indicator reaction, use is made of an imidazole derivative as the chromogen. The dye formed in the presence of peroxidase can be measured by reflectance photometry beyond the long-wave absorption bands of haemoglobin and bilirubin at 642 nm. We present in detail the results of the multicentre evaluation of the analytical properties of this new test principle. The data obtained show that Reflotron Creatinine (new) correlates well with the routine method Creatinine PAP, which was used as a comparison method, with respect to accuracy and precision and even surpasses it with respect to specificity. Advantages over the first generation of Reflotron Creatinine are: shorter reaction time, longer stability of the reagent carrier, no interference by bilirubin and reduced interference by haemoglobin. PMID- 8357942 TI - Falsely low results in CA 125 determination due to anti-idiotypic antibodies induced by infusion of [131I]F(ab')2 fragments of the OC125 antibody. AB - We investigated a one-step immunometric CA 125 assay, which employs new anti-CA 125 antibodies as capture antibodies and OC125 antibodies for detection, for interference due to antibodies induced by repeated administration of F(ab')2 fragments of the anti-CA 125 antibody OC125. Testing 33 samples, obtained from 13 patients treated with OC125 fragments, we found falsely high CA 125 concentrations only in samples with exceptionally high concentrations of both anti-idiotypic antibodies and non-specific human anti-mouse antibodies. In contrast, the recovery of added CA 125 was already diminished in the presence of low anti-idiotypic antibody concentrations. Both interferences disappeared after removal of serum IgG. It was possible to eliminate the falsely high results, but not the reduction in recovery rate, by adding non-specific murine IgG. When the binding of the detector antibodies was performed in a separate incubation step, no reduction in recovery rate was observed. Our results suggest that non-specific human anti-mouse antibodies are responsible for falsely high results. The reduction in the recovery rate is obviously due to an inhibition of the binding of OC125 detector antibodies by anti-idiotypic antibodies. In patients receiving OC125 antibodies CA 125 can be measured using OC125 detector antibodies if a two step assay is performed. An increase in CA 125 following OC125 infusion should be confirmed after the addition of non-specific murine IgG. PMID- 8357944 TI - Ibuprofen toxicity. A review of adverse reactions and overdose. PMID- 8357945 TI - Impurities in organic synthetic drugs: a review of regulatory and toxicological considerations. PMID- 8357946 TI - Famous names in toxicology. Paracelsus--born 500 years ago. PMID- 8357947 TI - Chloramphenicol toxicity. AB - Although high serum concentrations of chloramphenicol are related to toxicity, as shown experimentally and during treatment, the mechanism of toxicity remains unclear. Published work suggests that relatively minor metabolites may be causally related to toxic reactions in vitro and some of these metabolites have been detected in sera from treated patients. It is possible that all the major toxic manifestations of chloramphenicol may be explained by attack by free radicals. Depletion in compounds acting as cellular antioxidants, such as glutathione and vitamin E, may conceivably increase the vulnerability of an individual to chloramphenicol toxicity, while supplementation with an antioxidant might protect against it. Research into the metabolism of chloramphenicol and into the mechanism of its toxicity has declined since early work in the 1950s and 1960s, but its continuing use worldwide means that there is justification for renewed interest in the toxicology of this useful antibiotic. PMID- 8357948 TI - Do chloramphenicol blood dyscrasias occur in Hong Kong? PMID- 8357949 TI - Two-dimensional tortuosity of the superficial femoral artery in early atherosclerosis. AB - Tortuosity of an artery can disturb fluid mechanics and cause flow separation, which might in turn promote atherogenesis. This study discusses theoretically several quantitative measures of arterial tortuosity and curvature in two dimensions and tests them with computations from digitized femoral arteriograms. When reproducibility, sensitivity to scaling and computational procedure, and agreement between the measures were all taken into account, the total curvature and distance factor were considered the most suitable measures. Significant correlations were found between tortuosity and atherosclerosis measures, but the interpretation of this finding is not straightforward. PMID- 8357950 TI - Morphogenic effects of endothelin-1 on vascular smooth muscle cells. AB - Endothelin-1 (ET-1), a vasoconstrictor peptide produced by endothelial and vascular smooth muscle cells (VSMC) might play a role in vascular remodelling. To investigate the proposed 'mitogenic' potential of ET-1, we examined the effects of chronic exposure of VSMC to ET-1 on cell cycle, growth/proliferation and differentiation under essentially mitogen-free culture conditions. Bulk cultures of thoracic aortic VSMC of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats, although exhibiting genetically determined differences in growth/proliferation (due to shortened G1 and G2 phases in SHR VSMC), respond in a similar manner to ET-1 exposure: long-term exposure (12-15 days) of VSMC from both sources to ET-1 in nonmitogenic medium did not promote cycling of cells. On the contrary, ET-1 attenuated the cycling of VSMC which had already cycled beyond the S phase. For cells which had not cycled beyond the S phase, ET 1 interrupted progression through the cell cycle at the late G1/early S phase. The specific ability of SHR VSMC to grow in mitogen-free medium was abolished by ET-1, most likely via down-regulation of platelet-derived growth factor (PDGF) alpha receptors. Subsequent to ET-1 exposure, VSMC expressed increased levels of mRNA and protein for smooth-muscle-specific alpha-actin. However, expression of smooth muscle alpha-actin did not predominate over beta-actin as observed for adult contractile VSMC in vivo. The ET-1-induced expression of smooth-muscle specific alpha-actin mRNA was dose dependent (EC50 approx. 2 x 10(-9) M), and alpha-actin protein expressed was associated with organized actin fibers. PMID- 8357951 TI - Eicosapentaenoic acid potentiates the production of nitric oxide evoked by interleukin-1 beta in cultured vascular smooth muscle cells. AB - Experiments were designed to determine whether the omega 3-unsaturated fatty acid eicosapentaenoic acid affects the production of nitric oxide evoked by interleukin-1 beta in cultured vascular smooth muscle cells. Incubation of cultured rat or human aortic smooth muscle cells with interleukin-1 beta evoked a time- and concentration-dependent release of nitrite, an oxidation product of nitric oxide. The exposure of cells to interleukin-1 beta in combination with eicosapentaenoic acid caused a significantly larger production of nitrite than that evoked by the cytokine alone. The potentiation by eicosapentaenoic acid was concentration-dependent. The production of nitrite evoked by equieffective concentrations of interleukin-1 beta in the presence and absence of eicosapentaenoic acid were inhibited to a similar extent by nitro L-arginine (an inhibitor of nitric oxide synthase), transforming growth factor beta 1, platelet derived growth factorAB and thrombin. The addition of interleukin-1 beta activated smooth muscle cells to suspensions of washed and indomethacin-treated platelets inhibited the aggregation caused by thrombin. The inhibitory effect was enhanced when the smooth muscle cells were exposed to the cytokine in the presence of eicosapentaenoic acid prior to the experiment. Smooth muscle cells exposed to interleukin-1 beta and eicosapentaenoic acid did not affect platelet aggregation in the presence of oxyhemoglobin or methylene blue. Untreated cells or cells exposed to the fatty acid alone did not have such effects. These observations suggest that eicosapentaenoic acid potentiates the production of nitric oxide evoked by interleukin-1 beta in vascular smooth muscle. PMID- 8357952 TI - Renal versus femoral hemodynamic response to endothelium-derived relaxing factor synthesis inhibition. AB - Systemic inhibition of endothelium-derived relaxing factor (EDRF) synthesis leads to acute hypertension and increased peripheral vascular resistance. The changes in vascular resistance are not evenly distributed to all vascular beds. In this study, we compared the renal and femoral hemodynamic responses to EDRF synthesis inhibition. Renal blood flow (RBF) and femoral blood flow (FBF) were assessed in the presence and absence of DuP 753, an angiotensin II receptor antagonist. Inhibition of EDRF synthesis by a bolus dose of Lw-nitroarginine methyl ester (L NAME) increased blood pressure (BP) by 21 +/- 1 mm Hg (p < 0.001) and decreased RBF by 32 +/- 5% (from 5.9 +/- 0.5 to 3.9 +/- 0.3 ml/min/g kidney weight; p < 0.005) while FBF remained unchanged (9.5 +/- 0.4 versus 9.4 +/- 0.4 ml/min). Renal vascular resistance (RVR) increased by 83 +/- 16% (p < 0.001), compared with only a 24 +/- 6% increase in femoral vascular resistance (FVR; p < 0.005). To eliminate the influence of systemic hypertension, we returned organ perfusion pressure to pre-L-NAME levels by partial aortic constriction. The kidney maintained RBF by decreasing RVR by 8 +/- 2% (p < 0.02), while FBF decreased by 15 +/- 5% (p < 0.01). When rats were pretreated with DuP 753, L-NAME still increased BP by 22 +/- 2 mm Hg, but RVR increased by only 26 +/- 5% (from 13.2 +/ 1.6 to 16.8 +/- 2.7; p < 0.01) and RBF did not change. DuP 753 had no effect on the femoral vascular response to L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357953 TI - Contractility of the rabbit abdominal aorta 4 days after endothelium denudation. AB - The purpose of this study was to evaluate contractility of the rabbit abdominal aorta 4 days after de-endothelialization by balloon catheter. The isometric tension of ring-segments in response to vasoactive agents was monitored. A significant enhancement of contraction to noradrenaline and serotonin was found in aortas 4 days after endothelium denudation as compared with controls with endothelium. The enhancement, however, did not differ from that found already in acutely denuded vessels (immediate denudation). No significant difference in contractility to potassium chloride was found in either group of denuded preparations as compared with controls. The sensitivity to all three vasoactive agents (EC50) was not influenced by denudation. These results indicate that changes in the contractility of denuded vessels are predominantly a consequence of lacking the endothelium as a producer of endothelium-derived relaxing factor. The access of mitogens to the media does not seem to interfere with the magnitude of contraction 4 days after denudation. PMID- 8357954 TI - Arginine vasopressin increases perinuclear [Ca2+] in single cultured vascular smooth muscle cells of rat aorta. AB - The effects of arginine vasopressin (AVP, 10(-7) M) on the spatial dynamics of intracellular [Ca2+] in single cultured smooth muscle cells of the rat aorta were studied by digital imaging microscopy using the fluorescent Ca2+ indicator fura 2. The nuclear and cytosolic regions were distinguished by the fluorescent image excited at 380 nm. Changes in intracellular [Ca2+] were expressed as percent increases in the ratios of fluorescence intensity at 500 nm excited by 340 and 380 nm. AVP increased the nuclear and cytosolic [Ca2+] in Ca(2+)-containing (control) (285 +/- 27 and 172 +/- 22%, respectively) or Ca(2+)-free (203 +/- 26 and 121 +/- 15%, respectively) solutions. However, caffeine (20 mM) and ryanodine (20 microM) greatly attenuated the [Ca2+] increase induced by AVP in both regions (61 +/- 21 and 42 +/- 15%, respectively). On the ratio image, the nuclear region was discriminated from other regions at the peak response to AVP in preparations treated with caffeine and ryanodine, whereas the outline of the nuclear region was indistinct in untreated preparations. The finding implies that caffeine- and ryanodine-responsive Ca2+ storage sites may exist in the region surrounding the nucleus. The results suggest that the region surrounding the nucleus may be one of the important Ca2+ storage sites with regard to the responses of rat aortic smooth muscle cells to AVP. PMID- 8357955 TI - Reduction of vein graft intimal hyperplasia by ex vivo treatment with desferrioxamine manganese. PMID- 8357956 TI - Human kappa chain expression in a lambda phage vector: methods of isolating amplified cDNA affects cloning efficiency. AB - Three common methods of isolating amplified DNA were evaluated for their effects on cloning efficiency in a phage vector designed to express human kappa chain. The "glass milk" technique gave higher cloning efficiency and protein expression than phenol-chloroform extraction or microfiltration. This shows that the quality of amplified cDNA should be considered when studying the human antibody repertoire using this vector system. PMID- 8357957 TI - Specific immunosuppression of human anti-murine antibody responses in hu-PBL-SCID mice. AB - Severe combined immunodeficient (SCID) mice were reconstituted with normal human peripheral blood leukocytes (PBLs) and were shown to produce a human anti-mouse immunoglobulin antibody response on immunization with heat-treated murine monoclonal IgG1 antibody to ovalbumin, referred to as ha-Mab-2. The human anti mouse antibody response was proportional tot the number of B cells and mononuclear cells transferred from a given batch of PBL. However, pretreatment of hu-PBL-SCID mice with a tolerogenic covalent conjugate of monomethoxypolyethylene glycol (mPEG) and Mab-2 suppressed this response on subsequent injections of ha Mab-2, and this suppression was shown to be antigen-specific, i.e., it did not suppress the antibody response to ovalbumin and did not affect the level of production of human immunoglobulin of hu-PBL-SCID mice. The suppression was due to the generation of human suppressor CD8+ T (Ts) cells, which down regulated CD4+ helper T cells in an antigen and HLA class I specific manner, i.e., these findings were in accord with the previously shown immunosuppressive effect of tolerogenic mPEG conjugates in normal mice. PMID- 8357958 TI - Suppression of human anti-mouse idiotypic antibody responses in hu-PBL-SCID mice. AB - Severe combined immunodeficient (SCID) mice were engrafted with appropriate numbers of T cells and B plus mononuclear cells, which had been fractionated from normal human peripheral blood leukocytes (hu-PBLs). Treatment of these hu-PBL SCID mice with a tolerogenic covalent conjugate of monomethoxypolyethylene glycol (mPEG) and an anti-ovalbumin, IgG1 murine monoclonal antibody, Mab-2, suppressed the human anti-mouse antibody responses to both the common (gamma 1,kappa) and the idiotypic determinants of Mab-2. Moreover, the Mab-2(mPEG)36 conjugate suppressed the immune responses of hu-PBL-SCID mice to the common and idiotypic determinants of murine monoclonal antibodies to the 2,4-dinitrophenyl residue and to human CD4, consisting also of gamma 1 and kappa chains. It is concluded that a tolerogenic mPEG conjugate of a murine monoclonal antibody induces pan suppression of the human lymphoid system with respect to other murine monoclonal antibodies that share the isotypic determinants of the original one (here, Mab-2) incorporated in the conjugate. Hence, it may be anticipated that human anti-mouse antibody responses to any murine IgG monoclonal antibody would be suppressed by one of eight mPEG conjugates, each incorporating one of the four subclasses of IgG and one of the two light chains. PMID- 8357959 TI - Immunoglobulin V region heavy and light chain gene sequences of the lymphoblastoid cell line GM 4672. AB - GM 4672 is an IgG2 kappa-producing lymphoblastoid cell line derived from a patient with multiple myeloma. It has been used by many laboratories as a fusion partner for the production of human-human hybridoma monoclonal antibodies. GM 4672 immunoglobulin variable region heavy and light chain family usage was originally assigned to VH1 and VK1, respectively. This assignment was based on the positions of [3H]leucine of the heavy and light chain proteins using the Edman degradation method. Using the polymerase chain reaction and variable region leader primers and constant region primers, we report here the immunoglobulin variable region gene sequence expressed by GM 4672. The VH region belongs to the VH4 family and is most homologous with the V71-2 (87.9%), DK1, and JH4 germline genes. The entire heavy chain V region contained 41 mutations in 36 codons and included 11 N nucleotide additions flanking the D region. GM 4672 VK region contained a VK1 gene rearranged with a JK4 gene. The VK germline gene used by GM 4672 light chain was not identified but showed the most homology with Vb' germline gene (87.7%). When compared to Vb' and JK4 genes, there were 37 mutations in 30 codons with evidence of antigen selection as determined by the replacement to silent mutation ratio in the complementarity-determining regions. The high frequency of mutations in the V region genes of GM 4672 is comparable to the sequences of other myeloma proteins. PMID- 8357960 TI - Dendritic cell activity against primary tumors: an overview. AB - Bone marrow-derived dendritic cells (DC) function as antigen presenting cells (APC). Little is known of their capability to exert regulatory effects on the epithelial cells in various organs. It was reported that injection of the bacterial cell wall preparation OK432 into mouse skin resulted in the activation of IL-1 and TNF-alpha gene expression in Langerhans cells (LC). In addition to studies on LC/DC in normal tissues, numerous investigators reported that DC can infiltrate primary tumors in experimental animals and humans and cause tumor regression. Human tumors in which DC infiltrates were detected did not develop metastases. The presence of DC in tumor biopsies correlated with the survival of patients. Absence of DC from tumors suggested poor prognosis. Activation of DC by immunomodulators seemed to enhance the ability of DC to prevent the development of metastatic tumors. Information on the role of DC as anticancer cells was recently reviewed, but information on the molecular basis of the anticancer activity of DC is needed. Another problem which needs to be answered is the ability of some tumors to prevent DC from entering the tumor. It is possible that DC and tumor cells, interact and counteract by releasing cytokines which abrogate tumor cells or DC, respectively. In the present analysis the DC responses to extrinsic cytokines and immunomodulators will be discussed. The ability of DC to induce the expression of the nitric oxide synthase gene will be discussed in relation to the anticancer activity of DC and in comparison with the reported anticancer activity of macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357961 TI - The dendritic cell system and anti-tumour immunity. AB - Dendritic cells (DC) are essential for the initiation of T- and T-dependent immune responses by virtue of their capacities to acquire, process and present antigens and to deliver activation signals to mature resting T cells. In contrast, antigen presentation by other types of antigen-presenting cells (APC) may lead to peripheral T cell tolerance. This paper reviews the immunobiology of DC, and considers the possibility that immune unresponsiveness of tumour-bearing hosts may be due to clonal anergy of T cells. An important issue is whether it is possible to use DC to vaccinate tumour-free individuals, to overcome the immunological unresponsiveness of tumour-bearing hosts, and ultimately to cause rejection of primary and metastatic cancers. PMID- 8357962 TI - Langerhans cells in epithelial skin tumors. A quantitative immunohistological and morphometric investigation. AB - In the present study we investigated whether there is a correlation between Langerhans cell density, peritumoral infiltrate or intraepithelial T-lymphocyte density within 17 epithelial skin tumors using immunohistologic and morphometric methods. We found a significant difference between seborrheic keratosis, basal cell carcinoma, and squamous cell carcinoma. No correlation was found between the Langerhans cell density and the number of intraepithelial T lymphocytes or between Langerhans cell density and the peritumoral infiltrate. A significant (inverse) correlation was found between mean nuclear area of the epithelial tissue and the number of Langerhans cells. These data might indicate that the number of Langerhans cells does not influence the extent of the anti-tumoral immune response, but that there is an association between the differentiation state of the epithelium and Langerhans cell density. PMID- 8357963 TI - Role of Langerhans cells and other dendritic cells in disease states. AB - Langerhans cells belong to the dendritic cell lineage and function as potent antigen-presenting cells in the skin epidermis. During the last decade, much has been learned on dendritic cell involvement in the pathogenesis of disease states. This review briefly summarizes our current understanding of the role played by Langerhans cells and other dendritic cells in the pathogenesis of immune mediated, neoplastic and infectious disorders. PMID- 8357964 TI - Dendritic cells prevent lymph node metastasis in patients with gastric cancer. AB - Infiltration of S-100 protein positive dendritic cells into tumor tissues was investigated immunohistochemically. Although the survival time of patients with Stage I, II or IV gastric cancer did not relate to the density of dendritic cells, survival time in Stage III patients correlated with the density of dendritic cells. In patients with a marked infiltration, survival time was longer than in cases of only a slight infiltration (P < 0.001). The frequency in the marked infiltration group at the mucosal stage did not change in proportion to invasion into the deeper layers. There was a similar incidence of lymph node metastasis between the marked and slight infiltration groups in each grade of tumor invasion. However, marked infiltration of dendritic cells prevented widespread nodal involvement beyond the primary node in cases of advanced cancer (P < 0.05). This may be one of the reasons why the infiltration of dendritic cells is clinically effective in patients with Stage III gastric cancer. PMID- 8357965 TI - Dendritic cells in esophageal cancer and lymph node tissues. AB - The density of infiltrating S-100 protein-positive dendritic cells (DCs) on histological sections and that of CD1- and L-M2 positive DCs on cryostat sections of esophageal dysplastic and cancerous lesions were examined. There was no significant correlation between the number of S-100 protein-positive DCs and the degree of dysplasia, tumor of S-100 protein-positive DCs and the degree of dysplasia, tumor differentiation, depth of invasion or lymph node metastasis of esophageal cancer, but the numbers of these cells in patients after preoperative radiotherapy were significantly lower than those in patients without radiotherapy. Immunohistochemical staining of cryostat sections with anti-CD1 antibody and L-M2 revealed that poorly differentiated squamous cell carcinoma (SCC) contained significantly more DCs than well differentiated SCC. Analysis of the numbers of Langerhans cells (LCs) and interdigitating cells (IDCs) revealed that well differentiated SCC contained 32.8% LCs and 67.2% IDCs, moderately differentiated SCC contained 37.0% LCs and 63.0% IDCs, and poorly differentiated SCC contained 2.1% LCs and 97.9% IDCs, the overall proportions being 24.2% for LCs and 75.8% for IDCs. Morphometrical analysis of regional primary lymph nodes revealed that the degree of paracortical hyperplasia with cancer metastasis was significantly higher than that without cancer metastasis, and that the degree of sinus hyperplasia with cancer metastasis was significantly lower than that without. Furthermore, lymph nodes with cancer metastasis contained significantly more S-100 protein-positive IDCs than those without.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357966 TI - Dendritic cells in various human thyroid diseases. AB - The aim of this study is to determine the presence of S-100 protein-positive and CD1-positive dendritic cells (DCs) in tissues with various human thyroid diseases. Infiltrating DCs were frequently observed in papillary carcinoma and Hashimoto's disease, and these DCs were composed primarily of IDCs. The number of DCs was closely correlated with the expression of thyrocytes for S-100 protein and Ia-antigen. These findings suggest that DCs may play an important role in the immunologic defence mechanisms against papillary carcinomas and in the progression and self perpetuation of autoimmunity. PMID- 8357967 TI - Antitumor activity of Langerhans cells in radiation therapy for cervical cancer and its modulation with SPG administration. AB - Correlations between infiltration of Langerhans cells (ILC) in tumor tissues and radiation curability were investigated in 449 patients with cervical cancer treated with radiation alone, including 390 squamous cell carcinomas and 59 adenocarcinomas. No significant difference in prognosis was noted in stage I, II, and IV squamous cell carcinomas between positive and negative ILC. However, in the patients with stage III squamous cell carcinoma, a significantly better survival was observed for patients with ILC than for those without, 10 year survival rates being 78% vs. 54%, P < 0.01. In adenocarcinoma, the patients with ILC also showed significantly better survival than those without ILC, the 10 years survival rates being 45% vs. 25%, P < 0.025. An analysis of failure patterns following radiation treatment demonstrated that the favorable prognosis in patients with ILC in squamous cell carcinoma was due to improvement of local control rates and somewhat lower metastatic rates, whereas in adenocarcinoma it was only due to better local control rate. The ILC was significantly associated with T-cell infiltration in tumor tissues. The immunological stimulation with Sizofiran in 20 patients led to an augmentation of ILC in tumor tissues. The present study suggests that the ILC in cancer tissues improves local response to radiation treatment partly by T-cell mediated anti-tumor activity. PMID- 8357968 TI - Modulation of antigen-presenting cell function as a potential regulatory mechanism in tumor-host immune reactions. AB - A growing body of information suggests that immunological defense mechanisms against newly emerging tumors may exist within the skin. In this regard, the recognition and presentation of tumor-associated antigens by cutaneous antigen presenting cells is a prerequisite for the establishment of specific tumor immunity. However, despite the recently demonstrated ability of normal I-A+ epidermal cells (Langerhans cells) to effectively present tumor-associated antigens in vivo, even tumors with recognizable antigenic epitopes can grow progressively in situ. Therefore, regulatory mechanisms within the local microenvironment may exist that control the ability of resident epidermal APC to initiate and to elicit protective immunity against incipient cutaneous neoplasms. This report reviews the role of APC in tumor immunity and the effects of cytokines and ultraviolet radiation (UVR) on tumor antigen presentation by epidermal APC. Our data suggest that these agents can significantly modify the ability of epidermal cells to present tumor-associated antigens and may therefore control the type and effectiveness of tumor immune responses in situ. Furthermore, the induction of primary tumor immunity and the elicitation of secondary immune responses are independently regulated and respond differently to cytokine application. PMID- 8357969 TI - Topical retinoic acid inhibits changes in Langerhans cell density during carcinogenesis. AB - Ultraviolet radiation (UVR), chemical carcinogens and contact sensitisers all reduce the density of Langerhans cells (LC) in murine epidermis; UVR also lowers the number of Thy-1 dendritic epidermal cells (Thy-1+ dEC). Topical application of all-trans retinoic acid (RA) renders these cells insensitive to UVR and the tumour promoter 12-0-tetradecanoylphorbol 13-acetate (TPA) but does not inhibit LC migration from the epidermis in response to a contact sensitiser. Additionally, when the diet of mice was supplemented with the retinoid temarotene, UVR was unable to reduce the number of LC or Thy-1+ dEC. Hence one of the anti-carcinogenic mechanisms of retinoids may be to protect LC from carcinogens. PMID- 8357970 TI - Epidermal Langerhans cells and prognosis of patients with mycosis fungoides and Sezary syndrome. AB - Langerhans cells (LC) (CD1a-positive dendritic epidermal cells) have been proposed to favour the pathogenesis of mycosis fungoides (MF) and Sezary syndrome (SS). We therefore examined the influence of LC retrospectively on the survival of 35 patients. Two clinical parameters (age, stage of disease) were additionally evaluated. LC densities were morphometrically assessed on immunohistochemically stained cryostat sections of the respective diagnostic specimen. Death resulting from MF and SS was significantly (p = 0.003) less frequent in patients with CD1a positive epidermal cell densities higher than 90 cells/mm2 (optimal break point) as compared with patients with lower numbers, independently of the stage of disease. This result suggests that LC have a significant impact on the prognosis of patients with MF and SS, playing an important role in the host defense mechanisms against these lymphomas. PMID- 8357971 TI - Bone marrow-derived dendritic cells and the protection against X-ray-induced thymic leukemia in mice. A new interpretation. AB - About forty years ago, Henry Kaplan and collaborators reported that four weekly X ray doses of 160 rads each were highly leukemogenic in C57BL mice. A single dose of 350 Rads had a week leukemogenic effect. These authors also demonstrated that lead shielding of the thigh during irradiation prevented the development of leukemia. They reported that intravenous injection of syngeneic bone marrow cells into irradiated mice facilitated the regeneration of the thymus and prevented the development of X-ray-induced tumors. We characterized the thymic Ia+ dendritic cells (DC) with the aid of a fluorescence-activated cell-sorter (FACS). It was found that exposure of mice to a leukemogenic regimen of fractionated X irradiation treatment led to a gradual decrease in the number of thymic DC. The disappearance of thymic DC and the development of leukemia were prevented by intravenous injection of syngeneic bone marrow or by lead shielding of the femur during irradiation. These results indicated that the fractionated irradiation caused a decline in the number of DC and, as a result, diminution of the natural defense against the developing tumor. Homing of the injected bone marrow DC into the thymus can be connected to the prevention of tumor development. Since leukemogenic T cells produce interleukin-4(IL-4), we tested the effect of the conditioned medium in which YAB-3 cells (tumorigenic Th cells: CD4+, CD8-, Thy 1+) were cultivated. Following injection of the conditioned medium into the mouse footpads, the number of skin Langerhans cells (LC) decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8357972 TI - The role of dendritic cells in the motility of melanoma cells in initial lymphatic metastasis. AB - Malignant melanoma is well known for its aggressive metastatic behavior, following upon the earliest initial stages. It is the purpose of this preliminary paper to add some new ideas, based on electron microscopy, to our understanding of the complex progression of malignant melanoma, using cutaneous melanoma as a model for the subtypes. Special attention is paid to cellular interaction in the progression of melanoma, with emphasis on the subtypes. PMID- 8357973 TI - Langerhans cell alterations in cutaneous carcinogenesis. AB - Analysis of the early stages of experimental skin cancer in mice has demonstrated that complete chemical carcinogens (e.g. DMBA or benzo(a)pyrene) and tumour promoters (e.g. TPA) but not tumour initiators (e.g. urethane) deplete or functionally alter epidermal Langerhans cells (LC). These changes result in altered local immunity as antigen presentation through LC depleted skin results in either immune tolerance due to the generation of suppressor T cells or anergy. Parallel studies in sheep have shown that, following the application of DMBA, depletion of LC is due to increased migration of these cells from the skin whereas tumour initiators did not alter LC migration. Likewise benzo(a)pyrene did not trigger enhanced LC migration from the epidermis. Experiments in mice suggest that part of this increased migration after the application of DMBA is due to the carcinogen being handled as an antigen by the epidermal LC. However, this fails to explain the prolonged migration which follows. The implication of these studies is that early in carcinogenesis, altered immune function occurs as a result of LC depletion/modification, allowing aberrant cells to proliferate in the absence of immune destruction. PMID- 8357974 TI - Epidemiological considerations in the role of dendritic/Langerhans cells in human cancer. AB - The roles of dendritic or Langerhans cells in human neoplasia have been studied in animal models and human subjects for some years. Much has already been learned concerning the operative immunological processes, relationships with other components of the reticuloendothelial system, and correlations with genetics and the aging process. Unfortunately, the present requirement for microscopic examination of human tissues to assay these cells greatly limits the types of study which can be under-taken and their scope. Investigations must presently be limited to human cancers occurring in readily accessible sites such as the uterine cervix, urinary bladder and skin. In the future, it is anticipated that new experimental approaches can be developed which permit the measurement of DC/LC activity levels without the need for biopsy specimens, thus greatly enhancing research possibilities in the important arena of biomedical investigation. PMID- 8357975 TI - Leukotriene A4 hydrolase: structural and functional properties of the active center. AB - Leukotriene (LT) A4 hydrolase (EC 3.3.2.6) is a bifunctional zinc metalloenzyme that possesses both an epoxide hydrolase activity, i.e., the well-known conversion of LTA4 into the proinflammatory substance LTB4, and a recently discovered peptidase activity. We have employed biochemical/kinetic analyses of native enzyme as well as site directed mutagenesis towards a recombinant enzyme to explore structural and functional properties of the enzyme active center. Thus, we have found that the peptidase activity is selectively stimulated by chloride ions, in a manner that suggests the presence of an anion binding site. Furthermore, a number of mutated enzymes have been constructed, expressed in E. coli, and purified to homogeneity to allow enzyme activity determinations and zinc analyses. The catalytic properties and zinc contents of these mutated enzymes establish the three zinc binding ligands of the protein and identify Glu 296 as a catalytic amino acid, directly involved in the peptidase, but not in the epoxide hydrolase reaction. In conclusion, our data provide strong evidence that the two catalytic activities of LTA4 hydrolase are exerted via non-identical but overlapping active sites. PMID- 8357977 TI - Drug inhibition and cellular regulation of prostaglandin G/H synthase isoenzyme 2. AB - Prostaglandin G/H synthase isoenzyme 2 (PGHS-2) was identified as an immediate early gene product induced by Rous sarcoma virus, serum, phorbol ester and a wide variety of other mitogens. Induction of PGHS-2 occurs through an increase in PGHS 2 gene transcription. Dexamethasone inhibits both the basal and induced levels of PGHS-2 mRNA. In contrast, PGHS-1 gene transcription rate, mRNA, and protein levels are unaffected by mitogens and dexamethasone. Post-transcriptional down regulation of PGHS-2 mRNA plays a significant role in causing dexamethasone's effect. Specific cell systems have been identified which allow selective analysis of PGHS-1 and PGHS-2 at the nucleic acid and protein levels. These cell systems indicate that PGHS-1 and PGHS-2 may have different sensitivities to non-steroidal anti-inflammatory drugs. Furthermore, inhibition of PGHS activity correlates well with suppression of the transformed phenotype in an in vitro cell model. PMID- 8357976 TI - Anti-inflammatory glucocorticoid action: inhibition of griPGHS, a new cyclooxygenase. AB - Our understanding of the anti-inflammatory actions of glucocorticoid hormones has significantly advanced in the past year with the discovery of a second cyclooxygenase gene which we call 'glucocorticoid-regulated inflammatory prostaglandin G/H synthase' (griPGHS). In mouse fibroblasts and human monocytes levels of griPGHS mRNA and protein rise dramatically in response to growth factors, cytokines, and oncogene activation. These inductions are markedly suppressed by the glucocorticoid hormone, dexamethasone. This stands in contrast to the behavior of the previously cloned cyclooxygenase (PGHS), which appears to be constitutively expressed. Thus far, data show that griPGHS is increased in many other systems where prostaglandin biosynthesis is regulated, including models of inflammation, tissue injury, and hormonal control of reproductive processes. Thus, griPGHS is likely to be a key mediator of many clinically relevant processes and as such represents an important target for both steroidal and nonsteroidal anti-inflammatory agents. PMID- 8357978 TI - Expression of the murine prostaglandin (PGH) synthase-1 and PGH synthase-2 isozymes in cos-1 cells. AB - Plasmid vectors were constructed which allowed expression of the mouse prostaglandin endoperoxide (PGH) synthase-1 and PGH synthase-2 isozymes in cos-1 cells. Efficient expression of the PGHS-2 isozyme required the truncation of the entire 3'-untranslated region of the PGHS-2 cDNA, possibly due to the presence of multiple AUUUA sequences which may destabilize the PGHS-2 mRNA. The length of the 3'-untranslated regions of the murine and ovine PGHS-1 isozymes, which do not contain AUUUA sequences, did not affect the efficiency of expression of these proteins. The murine PGHS-2 isozyme catalyzes the same cyclooxygenase and hydroperoxidase activities as the ovine and murine PGHS-1 isozymes. The maximal activities of the mouse enzymes expressed in cos-1 cells was about equal, but both were only about a third that seen with the sheep enzyme. Whether this reflects differences in the turnover rate of the mouse and sheep enzymes, or differences in the efficiency of expression in cos-1 cells is not known. PMID- 8357979 TI - Trp387 and the putative leucine zippers of PGH synthases-1 and -2. AB - The active site sequence 385-YHWH-388 of ovine prostaglandin endoperoxide synthase-1 (PGHS-1) has residues critical for cyclooxygenase and peroxidase catalysis. Tyr385 is essential for cyclooxygenase activity, His386, for peroxidase activity, and His388, for both activities. To determine the importance of Trp387, we used site-directed mutagenesis to replace Trp387 of PGHS-1 with arginine, phenylalanine, and serine. W387R and W387S lacked significant activity. W387F retained both cyclooxygenase and peroxidase activities. Thus, we conclude that Trp387 is not essential for catalysis by PGHS-1. Purified PGHS-1 is a homodimer. There are two putative leucine zipper regions in ovine PGHS-1 involving residues 345-366 and 487-508. We tested for a role of these leucine zippers as determinants of dimer formation. Helix-breaking proline mutations were introduced at Leu359 or Leu501. Neither of these residues proved to be essential for peroxidase activity; but, mutations at each residue greatly reduced or eliminated cyclooxygenase activity. Both mutant proteins chromatographed as dimers on Sephacryl G-200. Thus, neither of these putative leucine zipper regions alone is responsible for PGHS-1 dimer formation. PMID- 8357980 TI - Molecular cloning and expression of human thromboxane synthase. PMID- 8357982 TI - Physiological aspects of a high affinity binding site for pancreatic-type phospholipase A2. AB - We characterized a specific binding site for pancreatic-type phospholipase A2 (PLA2-I) in several tissues and cells. The PLA2-I binding protein was purified from bovine corpus luteum membranes, which had a mass of 190 kDa. The purified protein, which possessed a binding capacity with high affinity and specificity for a mammalian mature type of PLA2-I, was a glycoprotein having a core protein of approx. 150 kDa and its carbohydrate moieties might be required for ligand recognition. PLA2-I elicited several biological responses in tissues and cells; i.e., cell proliferation and eicosanoid production, possibly through its specific binding site. PMID- 8357981 TI - PAF-induced amplification of mediator release in septic shock: prevention or downregulation by PAF antagonists. PMID- 8357983 TI - Comparison of six mammalian lysophospholipases. AB - Lysophospholipases participate in the regulation of the levels of lysophospholipid, compounds with pleiotropic biological effects. Lysophospholipases were purified from a macrophage cell line (WEHI 265.1), a myelocytic leukemia cell line (HL-60) and peripheral blood eosinophils. WEHI 265.1 cells contain three lysophospholipases 28, 27 and 110 kDa as determined by polyacrylamide gel electrophoresis. The 110 kDa lysophospholipase also exhibits phospholipase A2 activity and appears to be identical to a previously described 110 kDa phospholipase A2. Similarly, the HL-60 cells have three lysophospholipases, the largest again a 110 kDa enzyme with phospholipase A2 activity and the smaller are 20 and 21 kDa. The low molecular mass lysophospholipases have distinctive chromatographic properties and amino acid compositions. However, the two low molecular mass enzymes from a given cell type are not radically different, e.g., 15 of the 20 amino acids of the C-terminal sequences of the HL-60 enzymes are identical. A single lysophospholipase, approx. 15 kDa, is a major eosinophil protein. This enzyme is different from those described above. PMID- 8357984 TI - Discovery of inhibitors of the 5-lipoxygenase activating protein (flap). PMID- 8357985 TI - A new class of leukotriene biosynthesis inhibitor: the development of MK-0591. AB - The evolution of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2 ylmethoxy+ ++)indol-2-yl]- 2,2-dimethylpropanoic acid), 12, a potent, orally active leukotriene biosynthesis inhibitor is described. MK-0591 is currently undergoing clinical evaluation as a potential agent for the treatment of asthma and inflammatory bowel disease. It acts through a novel mechanism by a specific interaction with a membrane protein, 5-lipoxygenase activating protein (FLAP), which has been shown to be essential for LT synthesis in inflammatory cells. A brief comparison of its biological activity with that of its progenitors MK-886 and L-674,636 is described. PMID- 8357986 TI - Inflammation, prostaglandins, and loss of function. PMID- 8357987 TI - The role of lipocortin 1 in the regulation of A549 cell proliferation and leukocyte migration. PMID- 8357988 TI - Prostaglandins in human cartilage metabolism. AB - (1) Human cartilage, both non-arthritic (N) and arthritic, is extremely sensitive to inhibition of glycosaminoglycan (GAG) synthesis by low concentrations of interleukin 1 (IL1). Local episodic synthesis and secretion of sub-nanogram concentrates of the cytokine is considered to play a significant role in the pathogenesis of osteoarthritis (OA) by preventing matrix repair. (2) The synthesis of IL1 can be controlled by prostaglandins (PGs), which may explain why the inhibitory action can be at least partially overcome by the action of the PG analogue Misoprostol in the dose range 10-100 ng/ml. It is suggested that this action is due to the suppression of a positive feedback loop for local IL1 synthesis and secretion. (3) Certain non-steroidal anti-inflammatory drugs (NSAIDs), in particular Indomethacin, Ibuprofen and Naproxen, cause inhibition of GAG synthesis, and hence may diminish the potentiality for repair in arthritic cartilage. It is suggested that these NSAIDs induce IL1 synthesis by diminishing PG levels. Misoprostol is able to reverse this effect at least partially. (4) Some cartilages in the presence of other NSAIDs, such as Diclofenac, which do not greatly inhibit chondrocyte matrix metabolism, nevertheless respond to the presence of Misoprostol by increased GAG synthetic activity. (5) The low mean matrix synthetic activity of human OA cartilages was significantly increased by Misoprostol. (6) Taken together, these studies substantiate the suggestion that Misoprostol is able to increase the repair potentiality of human OA cartilage, particularly during treatment with NSAIDs. PMID- 8357989 TI - Amino acid residues of 5-lipoxygenase-activating protein critical for the binding of leukotriene biosynthesis inhibitors. AB - 5-Lipoxygenase-activating protein (FLAP) plays an essential role in cellular leukotriene (LT) synthesis and represents the target of three classes of LT biosynthesis inhibitors. We have taken three approaches to localize regions of FLAP involved in the binding of these inhibitors. A comparison of the amino acid sequences of FLAP from eight mammalian species identifies regions of the protein which are highly conserved and consequently may be involved in functional and inhibitor binding properties of the protein. Conversely, amino acids not conserved amongst these species are unlikely to play an essential role in inhibitor binding. Immunoprecipitation of peptide fragments of FLAP cross-linked to photoaffinity analogues of LT biosynthesis inhibitors following site-specific peptide cleavage indicates that the inhibitor attachment site is amino-terminal to 72Trp. Taken together, the cross-species analysis and photoaffinity labelling studies suggest a region within the first hydrophilic loop of FLAP which may be important for inhibitor binding. Site-directed mutagenesis of human FLAP followed by the analysis of FLAP mutants in a radioligand binding assay was used to more accurately define critical amino acid residues within this region. Mutagenesis studies reveal that mutants containing deletions of amino acids in regions of FLAP not conserved between species retain the ability to specifically bind inhibitors. Furthermore, mutants containing deletions in a highly conserved region of the protein (residues 42-61) do not bind inhibitors. These studies have therefore localized specific amino acids of FLAP which are essential for inhibitor binding. The roles that these amino acids play in inhibitor binding and may play in 5-LO activation is under investigation. PMID- 8357990 TI - Formation and effects of leukotrienes and lipoxins in human bone marrow. AB - The present results demonstrate leukotriene and lipoxin synthesis in human bone marrow and link these findings to biological effects in the same tissue. However, the mechanisms behind the described effects on myeloid progenitor cell growth are presently unknown. It is conceivable that both leukotrienes and lipoxins may act through modulation of endogenous cytokine production. However, it should be noted, that these lipoxygenase products totally failed to induce colony growth in the absence of GM-CSF. Moreover, the role of lipoxins in the bone marrow needs to be further clarified, since LXA4 induced both synergistic (with GM-CSF) and antagonistic (with LTC4) effects on progenitor cell growth. A possible pathophysiological role for leukotrienes and lipoxins may be suggested in chronic myelogenous leukemia. Thus, the capacity of hematological cells from CML patients to synthesize LTC4 was significantly increased. In addition, we have recently reported that CML platelets possessed a markedly decreased ability to participate in transcellular synthesis of the potential inhibitors of myelopoiesis, LXA4 and 5(S),12(S)-diHETE (Stenke et al., 1991b). Moreover, the production of these compounds was totally abolished in platelets obtained from CML patients in blastic crisis. Further studies should aim at defining the mechanisms behind the regulatory actions of leukotrienes and lipoxins in normal and leukemic human myelopoiesis. PMID- 8357991 TI - Cell-cell interactions between platelets, macrophages, eosinophils and natural killer cells in thromboxane A2 biosynthesis. AB - Biosynthesis of thromboxane A2 (TxA2) during cell-cell interactions between platelets and alveolar macrophages, eosinophils and natural killer cells from guinea pigs has been investigated. The stimulation of platelets incubated with varying numbers of macrophages or eosinophils or NK cells with 5 microM ionophore A23187 has induced an increase of TxA2 synthesis in comparison to the sum of TxA2 production by each cell population stimulated alone. These results suggest that transcellular biosynthesis of TxA2 or cell cooperation occurred between platelets and the other cell population studied, which could correspond to cell-cell interactions of type IA and/or type III, according to the classification proposed by Marcus ((1986) Prog. Hemost. Thromb. 28, 127-42). When varying concentrations of platelets were incubated with the supernatant of cells previously stimulated with the ionophore A23187, an enhancement of TxA2 release was also observed. However, the supernatant of platelets stimulated with the ionophore A23187 did not induce a significant increase of TxA2 synthesis by the other cell populations. It is suggested that the biosynthesis of TxA2 during cell-cell interactions could account for the large amount recovered in biological fluid in various pathological conditions such as inflammatory and hypersensitivity reactions. PMID- 8357992 TI - Pathophysiologic role of eicosanoids in mesangial cell immune injury. AB - The pathophysiologic role of thromboxane and of arachidonate 5-lipoxygenation products in mediating changes in glomerular filtration rate (GFR) and renal blood flow (RBF) was investigated in a rat model of mesangial cell immune injury induced by a monoclonal antibody (ER4) directed against the mesangial cell membrane antigen, Thy 1. Following a single intravenous dose of the ER4 antibody acute decrements in GFR and RBF occurred at 1 h and were associated with enhanced glomerular leukocyte infiltration and synthesis of thromboxane A2, 12-HETE and LTB4. Pretreatment of animals with the thromboxane synthase inhibitor, Furegrelate, or the thromboxane receptor antagonist SQ-29,548 ameliorated or completely abolished the decrements in GFR and RBF without reducing glomerular leukocyte infiltration. Pretreatment with the arachidonate 5-lipoxygenase inhibitor MK-886 partially ameliorated the decrements in GFR and RBF, reduced the glomerular leukocyte infiltration and completely inhibited the glomerular LTB4 synthesis. Combined treatment with Furegrelate and MK-886 completely abolished the decrements in GFR and RBF as well as the glomerular synthesis of thromboxane, LTB4 and 12-HETE without altering glomerular leukocyte infiltration. These observations indicate that in mesangial cell immune injury thromboxane A2 and arachidonate 5-lipoxygenation products originating from infiltrating inflammatory cells mediate the decrements in GFR and RBF. Selective inhibition of these eicosanoids could be of benefit in clinical forms of mesangial nephritis. PMID- 8357993 TI - Interleukin 1 and interleukin 6 inhibition of mesangial cell proliferation: role of PGE2. PMID- 8357994 TI - Functional aspects of eicosanoid hydroxylation by lung and kidney cytochromes P450. Expression of cDNAs in mammalian cells and E. coli. AB - A gene subfamily of cytochromes P450 with catalytic activity toward various eicosanoid substrates has been studied with a variety of techniques in this laboratory, including purification and characterization, localization at the tissue and subcellular levels, physiological function, and cloning and expression in prokaryotic and eukaryotic systems. This paper reports experiments directed toward determining the function of the cytochrome P4504A metabolite, 20 hydroxyarachidonic acid (20-hydroxyeicosatetraenoic acid; 20-HETE), in cellular ion flux, immunohistochemical localization in lung, the effects of a mechanism based inhibitor, 12-hydroxy-16-heptadecynoic acid (12-HHDYA) on PGE1 omega hydroxylation, and the structure-function determinants which govern the activities of the enzymes encoded by this gene subfamily. PMID- 8357995 TI - Effect of aging on renal cytochrome P450-dependent arachidonic acid metabolism in Dahl rats. AB - We investigated the age-related changes of renal cytochrome P450-dependent arachidonic acid metabolism in 3-, 5-, 7-, 9-, 11-, 13- and 20-week-old male Dahl salt-sensitive (DS) and -resistant (DR) rats on a low sodium diet (0.3% NaCl). NADPH-dependent arachidonic acid metabolism was separated and measured by a radio HPLC system. The formation of 19-hydroxyeicosatetraenoic acid (HETE), 20 HETE, 1,20-dioic acid, epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acid (DHET) was age dependent in both DS and DR rats. omega-Hydroxylase (20-HETE and 1,20-dioic acid formation) and (omega-1)-hydroxylase (19-HETE formation) were increased from 3 to 5 weeks age, then decreased with aging in DR rats. Whilst omega/(omega-1)-hydroxylase activities were increased from 3- to 9-week-old rats, they decreased with aging in DS rats. omega/(omega-1)-Hydroxylase activities were higher in 3-5-week-old DR than DS rats. Epoxygenase activities (EETs and DHET formations) were highest in 3-week-old DS and DR rats, and showed no significant differences between two strains of rats at any ages tested. Renal cytochrome P450 dependent arachidonic acid metabolites have a wide and contrasting spectrum of biological and renal effects, and their relative rates of production may influence not only renal hemodynamics but also pro- and antihypertensive mechanisms of hypertension in Dahl rats. PMID- 8357997 TI - Formation by the endothelium of prostacyclin, nitric oxide and endothelin. AB - Prostacyclin and nitric oxide (NO) are two labile vasorelaxant and anti aggregatory substances which are released by receptor activation and in response to shear forces acting on endothelial cells, whereas the potent constrictor peptide, endothelin-1 (ET-1) is probably slowly released and exerts long-term control over the cardiovascular system. This review deals with the synthesis, release and pharmacological actions of prostacyclin, NO and ET-1, as well as the diseases which might result from their under- or over-production. PMID- 8357996 TI - Pheromonal and reproductive function of F prostaglandins and their metabolites in teleost fish. AB - Although the function of prostaglandins in fish reproduction has not been well studied, it is becoming increasingly clear that prostaglandin F2 alpha or a compound closely resembling it serves three critical roles mediating reproductive activities in teleost fish. First, it appears to play a paracrine role in the ovary stimulating and/or modulating follicular rupture. Second, circulating levels of F prostaglandins rise at the time of ovulation and travel to the brain where they elicit female sexual behavior. Third, recent studies indicate that F prostaglandin is metabolized and released to the water where it functions as a sex pheromone stimulating male sexual behavior. Although these roles have been best characterized in the goldfish, ongoing studies indicate that metabolites of prostaglandin F2 alpha may commonly function as pheromones in many fish. Many questions remain about the identity(ies), origins, and species-specificity of the prostaglandin pheromone. PMID- 8357998 TI - Diphenylmethylazine prostanoids with prostacyclin-like actions on human platelets. AB - A structure-activity study has been performed with respect to EP 157, a PGH2 analogue with a diphenylmethoxime omega-chain which behaves as an IP-receptor agonist. Bicyclo[2.2.1]heptene/heptane and bicyclo[2.2.2]octene/octane analogues were the most potent, with a cyclohexene analogue being less potent. Oxabicyclo[3.2.2]nonane, oxabicyclo[3.2.1]octane and oxabicyclo[2.2.1]heptane analogues were of low potency. Introduction of ether oxygen(s) into the omega chain generally maintained potency, whereas 6-oxa-1,4-m- and 6-oxa-1,4-p interphenylene analogues were inactive. Diphenylmethylazine analogues were also potent platelet inhibitors, but saturation of one of the phenyl rings abolished activity. Replacement of the oxime function by an ether group abolished activity. The results are discussed in relation to octimibate, a triphenylimidazoloxyalkanoic acid which is also an IP-receptor agonist, and to the possibility of IP-receptor subtypes. PMID- 8357999 TI - Thromboxane biosynthesis and metabolism in cardiovascular and renal disease. PMID- 8358000 TI - Marked overproduction of non-cyclooxygenase derived prostanoids (F2-isoprostanes) in the hepatorenal syndrome. AB - In spite of extensive searching for clues to the pathogenesis of the hepatorenal syndrome (HRS), its cause remains an enigma. The renal dysfunction in HRS has been attributed to intense but reversible renal vasoconstriction. This has engendered the hypothesis that the renal vasoconstriction is caused by a circulating factor. Patients with HRS exhibit chronic endotoxemia and may have tissue hypoxia, an environment conducive for the formation of free radicals. Recently, we discovered a series of novel prostaglandin (PG) F2-like compounds, termed F2-isoprostanes, that are produced in vivo as products of free radical catalyzed lipid peroxidation independent of the cyclooxygenase enzyme. One of these compounds, 8-epi-PGF2 alpha, has been found to be an extremely potent renal vasoconstrictor. Therefore, we quantified levels of these prostanoids in patients with HRS and compared them to various control groups. Plasma levels of these compounds were markedly elevated only in patients with HRS (113 +/- 30 pg/ml) (p < 0.01) compared to normal controls (19 +/- 7 pg/ml), patients with compensated liver disease (20 +/- 4 pg/ml), patients with decompensated liver disease (22 +/- 4 pg/ml), and patients with chronic renal failure (23 +/- 4 pg/ml). The increased levels of these compounds are unlikely the result of reduced hepatic and renal clearance of the compounds since levels are not markedly increased in patients with either decompensated liver disease or chronic renal failure alone. Whether F2-isoprostanes are the elusive mediators responsible for the renal vasoconstriction in HRS remains to be established. However, these findings do suggest that oxidant injury may be a fundamental abnormality involved in the pathogenesis of HRS. PMID- 8358001 TI - Prostaglandin D synthase is the key enzyme in the promotion of physiological sleep. PMID- 8358003 TI - Cellular origin of prostaglandins D2 and E2 in chick dorsal root ganglion: a biochemical and immunocytochemical study. PMID- 8358002 TI - 1,25-Dihydroxyvitamin D3 upregulates 5-lipoxygenase metabolism and 5-lipoxygenase activating protein in peripheral blood monocytes as they differentiate into mature macrophages. PMID- 8358005 TI - Control mechanisms for the ductus arteriosus and the perinatal pulmonary circulation. PMID- 8358004 TI - Phospholipase A2 (PLA2) activity in gerbil brain: characterization of cytosolic and membrane-associated forms and effects of ischemia and reperfusion on enzymatic activity. AB - Phospholipases A2 comprise a family of enzymes that hydrolyze the acyl bond at the sn-2 position of phospholipids to generate free fatty acids and lysophospholipids. In the central nervous system products of PLA2 regulate neurotransmission. In addition, the lysophospholipids, free fatty acids, eicosanoids, platelet activating factor and reactive oxygen species, generated by enhanced PLA2 activity and arachidonic acid metabolism, may be responsible for many destructive cellular processes in neuronal tissue. There are interactions between glutamate and PLA2 and its products which suggest that PLA2 activity plays an important role in excitotoxic neuronal cell injury associated with ischemia. Our laboratory has demonstrated that multiple forms of Ca(2+)-dependent PLA2 are present in the gerbil brain. These forms differ from previously described forms and from each other. After ischemia and reperfusion, cytosolic, mitochondrial/synaptosomal and microsomal PLA2 enzymatic activities are enhanced. These stable modifications of enzymatic activity cannot be explained by a direct effect of Ca2+ alone and our data suggest that regulatory influences other than Ca2+ may play an important role in PLA2 activation and mediation of cellular injury after an ischemic insult. PMID- 8358006 TI - The role of eicosanoids and endothelium-dependent factors in regulation of the fetal pulmonary circulation. AB - A complex interaction of mechanical, hormonal, vasoactive, morphological and gaseous factors is responsible for the transitional period and maintenance of these changes in the newborn period. Vasoactive eicosanoids, formed at multiple sites in the lungs exert multiple effects on the perinatal pulmonary circulation. By direct, as well as indirect interaction with other systems, eicosanoids appear to have a role in the rearrangement of the circulation at birth. At this time PGE1, acetylcholine, bradykinin, and endothelin appears to work, at least in part, to cause fetal pulmonary vasodilation via the release of EDRF. Products of the lipoxygenase pathway are powerful vasoconstrictors, but may not be important in regulation of high fetal pulmonary vascular tone or the pulmonary pressor response to hypoxia. PMID- 8358007 TI - PGE2 in the perinatal brain: local synthesis and transfer across the blood brain barrier. PMID- 8358008 TI - The role of prostanoids in neonatal cerebral blood flow autoregulation. AB - The regulatory role of prostanoids in acute cerebrovascular adaptations in newborns was determined using awake neonatal piglets (ages 0-5 days, n = 60). Cerebral blood flow (CBF) was measured by radiolabelled microspheres before and 45 s after intracarotid injections of PGE1 (0.1-10 micrograms/kg, n = 6), PGE2 (0.01-2 micrograms/kg, n = 6), PGF2 alpha (0.01 microgram/kg, n = 8) and PGI2 (0.1 microgram/kg, n = 6). CBF increased with PGE1 (10 micrograms/kg) by 39.5% and with all doses of PGE2 (p < 0.01) compared to zero dose. PGF2 alpha, a known adult vasoconstrictor increased total CBF from 97 +/- 8 to 130 +/- 14 ml/min per kg. PGI2 also increased CBF by 27% (p < 0.01). When CBF and prostanoid levels were measured with balloon catheters placed at the aortic root and the descending aorta and were inflated to adjust arterial blood pressure (BP) from 17 to 117 mmHg, sagittal sinus concentrations of prostanoids inversely correlated with total CBF (for PGs, tau = -0.52 to -0.66, p < 0.001; for TXB2, tau = -0.91 to 0.99, p < 0.0001). During hypotension (MABP < 50 mmHg) PGE, PGF2(2)alpha, 6-keto PGF1 alpha and TXB2 increased by 311 +/- 56, 330 +/- 50, 301 +/- 44 and 658 +/- 44%, respectively. Net cerebrovascular production [total CBF x (sagittal sinus arterial plasma prostanoid concentration)] of PGE, PGF2 alpha, and 6-keto-PGF1 alpha and TXB2 increased during hypotension compared to normotension (BP = 50-90 mmHg). At MABP = 91-117 mmHg, net production of prostanoids increased by 142 31%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358009 TI - Are prostaglandins mediators of mifepristone (RU 486)-induced cervical softening in early pregnancy? PMID- 8358010 TI - Mechanism of prostaglandin F2 alpha action in the ovary. PMID- 8358011 TI - Prostaglandin endoperoxide H synthase (PGHS) activity increases with gestation and labour in human amnion. PMID- 8358012 TI - Lipid mediators of implantation and decidualization. PMID- 8358013 TI - Site-directed mutagenesis of leukotriene A4 hydrolase: distinction of leukotriene A4 hydrolase and aminopeptidase activities. AB - Leukotriene (LT) A4 hydrolase catalyzes enzymatic hydration of LTA4 to biologically active substance, LTB4. Biochemical and immuno-histochemical studies have shown that this enzyme is ubiquitously distributed in various cells and tissues. A sequence domain of LTA4 hydrolase was found to be homologous to those of several zinc metalloproteases. Both native and recombinant enzymes were shown to possess equimolar zinc ion and aminopeptidase activity. To examine the molecular mechanism of this enzyme reaction, site-directed mutagenesis experiments were carried out. Single amino acid substitutions at Glu-297 revealed a distinction of two enzyme activities, and suggest that the glutamic acid residue at 297 is essential for aminopeptidase, while the side chain of Glu or Gln is required for LTA4 hydrolase activity. The loss of two enzyme activities in a mutant E319K confirmed the proposal that the presence of a zinc ion in the enzyme is required for both enzyme activities. PMID- 8358014 TI - The ocular effects of prostaglandins and the therapeutic potential of a new PGF2 alpha analog, PhXA41 (latanoprost), for glaucoma management. AB - In the early days of prostaglandin (PG) research, the infusion of large PG doses into rabbit eyes already traumatized by cannulation, led to the conclusion that PGs have a profound ocular hypertensive effect that is associated with a breakdown of the blood-aqueous barrier. In contrast, repeated topical application of PGs to nontraumatized eyes of several species other than rabbits has later been shown to yield a maintained ocular hypotensive effect, without barrier breakdown. Due to its excellent pharmacokinetic properties, the isopropyl ester form of PGF2 alpha (PGF2 alpha-IE) is a much more potent ocular hypotensive agent and appeared to be better suited for the management of glaucoma, than PGF2 alpha itself or any currently used glaucoma drug. However, even this prodrug caused clinically unacceptable foreign-body sensation and conjunctival hyperemia, which could be reduced, or eliminated, only by some modifications of the omega chain of PGF2 alpha-IE. One such analog, PhXA41, maintained highly significant IOP reduction in glaucoma patients even with once-daily application at the remarkably low concentration of 0.006%. Because PhXA41 reaches intraocular tissues and the systemic circulation in its de-esterified free-acid form, which is a good substrate for the PG transport system, it retains the most important pharmacokinetic advantages of topically applied PGF2 alpha-IE. However, its greatly reduced side effects give PhXA41 a clear therapeutic advantage over PGF2 alpha-IE, making it an effective new drug candidate for the long-term medical management of glaucoma. PMID- 8358015 TI - Intraocular pressure effects of selective prostanoid receptor agonists involve different receptor subtypes according to radioligand binding studies. AB - The receptors involved in the ocular hypotensive activity of prostaglandins (PG) E2 and F2 alpha in dogs and monkeys was investigated by examining the effects of putative receptor selective agonists on intraocular pressure. A diverse variety of receptor selective agonists lowered intraocular pressure in these species. Thus, FP-receptor agonists (17-phenyl PGF2 alpha, fluprostenol), agonists with potent activity at the EP3 receptor (MB 28767, sulprostone) and a prostanoid with activity at the EP2 receptor (11-deoxy PGE1) were all potent ocular hypotensives when administered as a single dose to dogs and monkeys or b.i.d. for 5 days in monkeys. These findings were regarded as surprising and prompted us to re-examine some aspects of the current classification for prostanoid receptors. At present certain receptor subtypes, notably EP2, EP3 and FP receptors, are defined only according to the potency rank order for agonists. In these studies, we employed radioligand binding studies to determine the degree of competition between prostanoid agonists claimed to be selective on the basis of functional assays. Competition studies with a diverse variety of prostanoids at the binding site for PGE2 and sulprostone on the myometrial plasma membrane prepared from the rat uterus were consistent with the presence of an EP3 receptor. Thus, EP3-receptor agonists (MB 28767 and sulprostone) potently inhibited PGE2 and sulprostone binding, whereas FP agonists (17-phenyl PGF2 alpha, fluprostenol), a DP agonist (BW 245C), an EP1 antagonist (AH 6809), an EP2 agonist (AH 13205) and TP-receptor ligands (BM 13505, I-BOP) afforded little or no inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358016 TI - Enhancement by GM-CSF of agonist-induced 5-lipoxygenase activation in human neutrophils involves protein synthesis and gene transcription. AB - We investigated the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the 5-lipoxygenase (5-LO) component of the leukotriene (LT) biosynthetic pathway of human neutrophils, in order to better understand the mechanism whereby the cytokine primes for LT synthesis. We found that GM-CSF increased 5-LO activation elicited by platelet-activating factor (PAF), N-formyl methionyl-leucyl-phenylalanine (fMLP), C5a, LTB4, IL-8 and calcium ionophore A23187, as determined by using an exogenous substrate. A close correlation was observed between the priming kinetics of GM-CSF on 5-LO activation and on LT synthesis; moreover, the effects of the cytokine on both 5-LO activation and LT synthesis were inhibited when the cells had been exposed to either the protein synthesis inhibitor, cycloheximide (CX), or the transcription inhibitor, actinomycin D (AD), prior to incubation with GM-CSF. These results raise the possibility that the priming by GM-CSF of LT synthesis may involve an effect of the cytokine on 5-LO protein synthesis and gene expression. PMID- 8358017 TI - Biochemical and molecular biological approaches to two types of arachidonate 12 lipoxygenase. PMID- 8358018 TI - Human 15-lipoxygenase: induction by interleukin-4 and insights into positional specificity. AB - Arachidonate 15-lipoxygenase (15-lipoxygenase) is a lipid-peroxidizing enzyme associated with specific inflammatory cells seen in asthma and atherosclerosis. In atherosclerosis, 15-lipoxygenase is induced in the macrophages of human and rabbit lesions and has been implicated in foam cell formation. In human lung, 15 lipoxygenase is preferentially expressed in airway epithelial cells and eosinophils. Our studies have focused both on the regulation of expression and on the structure-function relationships of the enzyme. To determine factors that could regulate expression, peripheral blood monocytes were purified and cultured with combinations of 18 factors. Only interleukin-4 (60 pM) induced 15 lipoxygenase mRNA, protein and enzymatic activity. Interferon-gamma (100 pM) inhibited the interleukin-4 dependent induction of 15-lipoxygenase. Results with cultured human airway cells were similar. These data suggest that expression of 15-lipoxygenase is regulated by interleukin-4, and that 15-lipoxygenase is a potential downstream effector molecule for this potent cytokine. In parallel studies, we have investigated determinants of positional specificity using site directed mutagenesis and bacterial expression of human 15-lipoxygenase. Hypotheses for mutagenesis were derived from an analysis of conserved differences among multiple lipoxygenase sequences. Switching four amino acids in 15 lipoxygenase to their counterparts in 12-lipoxygenase resulted in a variant enzyme that produced equal 12- and 15-lipoxygenation. Further analysis has identified two amino acids that completely control the positional specificity of 15-lipoxygenase. These data have led to a preliminary model of the enzyme's active site region. PMID- 8358019 TI - TIS10, a mitogen-inducible glucocorticoid-inhibited gene that encodes a second prostaglandin synthase/cyclooxygenase enzyme. PMID- 8358020 TI - Pharmacological profile of epiyangambin: a furofuran lignan with PAF antagonist activity. AB - The ability of a furofuran lignan, epiyangambin, to inhibit PAF-induced rabbit platelet aggregation in vitro and thrombocytopenia in rats was investigated. Epiyangambin dose-dependently inhibited PAF-induced platelet aggregation without modifying the amplitude of the maximal response, indicating a competitive antagonism. The IC50 value of epiyangambin for 10(-9) M PAF-induced aggregation was 6.1 x 10(-7) M and the Schild analysis provided a pA2 of 6.91 +/- 0.2 with a slope of 0.98 +/- 0.25 (n = 4) and a pKb of 6.94 +/- 0.19. Epiyangambin had no effect upon the platelet aggregation induced by collagen, thrombin or ADP. The in vivo administration of the lignan at 20 mg/kg significantly inhibited PAF-induced thrombocytopenia in rats. These data indicate that epiyangambin is a potent and selective antagonist of PAF both in vitro and in vivo. PMID- 8358021 TI - Involvement of platelet-activating factor (PAF) in endotoxin- or ischaemia induced intestinal hyperpermeability in the rat. AB - We have investigated the influence of BN 50727, a PAF antagonist, and allopurinol, a free radical scavenger, on the damaging effects of ischaemia reperfusion and endotoxin in the small intestinal mucosa. Using a rat experimental model, we determined the alterations in intestinal permeability and mucosal levels of PAF and lysoPAF following ischaemia or intravenous administration of endotoxin. Both of these treatments increased intestinal permeability and enhanced PAF levels in the mucosa. Preventive oral or intraduodenal administration of BN 50727 reduced both of these effects, by decreasing mucosal PAF formation, probably as a result of neutrophil infiltration and activation reduction. Pretreatment of the rats with allopurinol also resulted in similar protection except that the free radical scavenger was unable to inhibit the increase in PAF levels after ischaemia, suggesting that oxidative reagents are implicated in this pathology to a much greater extent than PAF. PMID- 8358022 TI - Stimulation of PGE2 synthesis in a co-culture of periosteal fibroblasts and osteoblast-like cells by parathyroid hormone. AB - In previous experiments, we demonstrated that hPTH 1-34 activates PGE2 synthesis and calcium mobilization by chick calvaria. In this report, we started to search for the PTH responsible cell population in this bone tissue. When the chick calvariae were subjected to sequential enzyme digestion, we found that the third cell population were the cells that reacted to human PTH 1-34 and bovine PTH 1 34. A subsequent procedure was performed using the cells isolated from enzyme digestion and separated into two distinct populations--periosteal fibroblasts (PF) and osteoblast-like cells (OB)--by a two-step density gradient of Percoll. We found that PF and OB cells alone did not respond to PTH in terms of PGE2 synthesis. However, when these two cell populations were mixed in the proportion of 50:50, the synthesis of PGE2 and PGF2 alpha was increased significantly by the treatment of PTH and calcitonin. No effects were demonstrated in the mixing proportions of 30:70 and 70:30. These results suggest that PTH responsiveness may need a local interaction between periosteal fibroblasts and osteoblast-like cells residing in chick calvaria. PMID- 8358023 TI - Leukotriene synthesis in U937 cells expressing recombinant 5-lipoxygenase. AB - The U937 human promyelocytic cell line does not express 5-lipoxygenase, but does express 5-lipoxygenase-activating protein (FLAP). U937 cells do not synthesize leukotrienes after stimulation by calcium ionophore A23187. Dimethyl sulfoxide (DMSO) differentiation of U937 cells, towards a more mature monocyte-macrophage lineage, induces the expression of FLAP but not 5-lipoxygenase. These DMSO differentiated U937 cells also lack the ability to synthesize leukotrienes. We infected viral RNA coding for 5-lipoxygenase into U937 cells using a retroviral vector and measured the synthesis of 5-lipoxygenase, FLAP, leukotrienes and 5 hydroxyeicosatetraenoic acid (5-HETE) by these cells after stimulation with A23187. Undifferentiated U937 cells infected with 5-lipoxygenase RNA expressed 5 lipoxygenase and FLAP but neither leukotrienes nor 5-HETE were detected after these cells were stimulated with A23187. Exposure of the 5-lipoxygenase-infected U937 cells to DMSO increased the expression of 5-lipoxygenase and FLAP, and these cells produced leukotrienes and 5-HETE in response to A23187. The synthesis of these products was inhibited by MK-886, a compound which specifically binds to FLAP. PMID- 8358024 TI - Effect of leukotrienes on sheep airway smooth muscle. AB - The effects of leukotrienes (LT) C4, LTD4, LTE4 and LTB4 on the development of isometric tension by sheep airway smooth muscle were determined in a tissue bath. LTE4 (1.5 x 10(-7) M) had no contractile effect. LTB4 contracted only lung parenchymal strips. LTC4 (8 x 10(-8) M) and LTD4 (1.1 x 10(-7) M) caused contractions in trachea, bronchi and lung parenchyma that developed slowly and persisted. The tracheal contractions caused by LTD4 and ACh were potentiated approx. 30% by the cyclooxygenase inhibitor meclofenamate (10(-6) M). Meclofenamate had no effect on leukotriene induced contractions in bronchi or lung parenchymal strips. The bronchodilator prostaglandins PGI2 and PGE2 were released from sheep trachea at rest and after contraction by LTD4. Inhibition of their release by meclofenamate may explain the potentiation of LTD4 contractions by meclofenamate. In vitro, LTD4 and LTC4 have potent contractile effects on sheep airway smooth muscle that are not mediated by the secondary release of constrictor cyclooxygenase products. These leukotrienes may play a substantial role in the pathogenesis of allergen and endotoxin induced lung mechanics changes in sheep. PMID- 8358025 TI - Activation of phospholipases D and A by amphiphilic cations of cultured LA-N-2 cells is G protein- and protein kinase C-independent. AB - Several amphiphilic cations such as mepacrine, desipramine, didodecyldimethylamine, chlorpromazine, oleylamine and W-7 activated the phospholipase D (PLD) activity of cultured LA-N-2 cells. These compounds, except for oleylamine, provoked the release of fatty acids, suggesting phospholipase A activation. Melittin, a PLA2 stimulator, caused the robust release of the free fatty acids but was a poor PLD activator. Although PLD could be activated by GTP gamma S, the stimulation by these amphiphilic cations was not abolished by GDP beta S, an inhibitor of G protein function. There was no change in the PLD activation by these amphiphilic cations by DiC8, a PKC activator, or by H-7, a PKC inhibitor or in PKC down-regulated cells. PMID- 8358026 TI - Expression of the Arabidopsis AtAux2-11 auxin-responsive gene in transgenic plants. AB - Five constructions containing deletions of the promoter from an auxin-inducible gene of Arabidopsis thaliana, AtAux2-11, were fused to the coding region of the reporter gene LacZ, which encodes beta-galactosidase, and a polyadenylation 3' untranslated nopaline synthase sequence from Agrobacterium. These chimeric genes were introduced into Arabidopsis by Agrobacterium tumefaciens-mediated transformation, and expression of the gene was examined by spectrophotometric and histochemical analyses. A 600 bp fragment from the AtAux2-11 promoter conferred histochemical patterns of staining similar to the longest 5' promoter tested, a 3.0 kb fragment. Localization of AtAux2-11/LacZ activity in the transgenic plants revealed spatial and temporal expression patterns that correlated with tissues and cells undergoing physiological processes modulated by auxin. LacZ activity was expressed in the elongating region of roots, etiolated hypocotyls, and anther filaments. Expression was detected in the vascular cylinder of the root and the vascular tissue, epidermis, and cortex of the hypocotyl, and filament. The AtAux2 11/LacZ gene was preferentially expressed in cells on the elongating side of hypocotyls undergoing gravitropic curvature. Expression of the chimeric gene in the hypocotyls of light-grown seedlings was less than that in etiolated seedling hypocotyls. The AtAux2-11/LacZ gene was active in the root cap, and expression in the root stele increased at sites of lateral root initiation. Staining was evident in cell types that develop lignified cell walls, e.g. trichomes, anther endothecial cells, and especially developing xylem. The chimeric gene was not expressed in primary meristems. While the magnitude of expression increased after application of exogenous auxin (2,4-D), the histochemical localization of AtAux2 11/LacZ remained unchanged. Transgenic plants with a 600 bp promoter construct ( 0.6 kb AtAux2-11/LacZ) had higher levels of basal and auxin-inducible expression than plants with a 3.0 kb promoter construct. Transgenic plants with a -500 bp promoter had levels of expression similar to the -3.0 kb construct. The -0.6 kb AtAux2-11/LacZ gene responded maximally to a concentration of 5 x 10(-6) to 5 x 10(-5) M 2,4-D and was responsive to as little as 5 x 10(-8) M. The evidence presented here suggests that this gene may play a role in several auxin-mediated developmental and physiological processes. PMID- 8358027 TI - Investigation of the mechanism underlying the inhibitory effect of heterologous ras genes in plant cells. AB - The ras genes from yeast and mammalian cells were fused to plant expression promoters, and introduced into plant cells via Agrobacterium, to study their effect on cell growth and development. All introduced ras genes had a strong inhibitory effect on callus and shoot regeneration from plant tissues. This is consistent with earlier findings that heterologous ras genes were highly lethal to protoplasts following direct DNA uptake. These effects could not be reversed by increasing exogenous or endogenous cytokinin levels. These effects were also independent of the v-Ha-ras mutations in functionally important regions of Ras proteins such as effector-binding and membrane-binding sites. Similarly, co transformation with the genes encoding the Ras-negative regulators, GTPase activating protein and neurofibromin did not affect the ras inhibitory effect, indicating that the mechanism of ras inhibition of plant cells is not related to normal ras cellular functions. This conclusion was supported by further studies in which ras gene expression was modified using various promoters and antisense constructs. The introduced ras sequences remained fully inhibitory regardless of which promoters (inducible or tissue-specific) or which orientations (sense or antisense) were tested. This strongly suggests that the ras DNA sequence itself, rather than the Ras protein or ras mRNA, is directly involved in the inhibitory effect. The mechanism underlying this novel phenomenon remains unknown. Introduced ras genes may inhibit plant cell growth by inducing co-suppression of unknown endogenous ras or ras-related genes, thereby leading to the arrest of cell growth. PMID- 8358028 TI - Purification of chloroplast elongation factor Tu and cDNA analysis in tobacco: the existence of two chloroplast elongation factor Tu species. AB - We have purified a chloroplast elongation factor Tu (EF-Tu) from tobacco (Nicotiana tabacum) and determined its N-terminal amino acid sequence. Two distinct cDNAs encoding EF-Tu were isolated from a leaf cDNA library of N. sylvestris (the female progenitor of N. tabacum) using an oligonucleotide probe based on the EF-Tu protein sequence. The cDNA sequence and genomic Southern analyses revealed that tobacco chloroplast EF-Tu is encoded by two distinct genes in the nuclear genome of N. sylvestris. We designated the corresponding gene products EF-Tu A and B. The mature polypeptides of EF-Tu A and B are 408 amino acids long and share 95.3% amino acid identity. They show 75-78% amino acid identity with cyanobacterial and chloroplast-encoded EF-Tu species. PMID- 8358029 TI - Transgenic potato plants overexpressing the pathogenesis-related STH-2 gene show unaltered susceptibility to Phytophthora infestans and potato virus X. AB - The STH-2 gene is rapidly activated in potato leaves and tubers following elicitation or infection by Phytophthora infestans. However, its biochemical function remains unknown. In order to ascertain if STH-2 protein is directly involved in the defense of potato against pathogens, the STH-2 coding sequence under the control of the CaMV 35S promoter was introduced into potato plants. Transgenic plants expressing the STH-2 gene were analyzed for an altered pattern of susceptibility to a compatible race of P. infestans and to potato virus X. Results indicate that constitutive expression of the STH-2 gene did not reduce susceptibility of potato to these pathogens. PMID- 8358030 TI - WIP1, a wound-inducible gene from maize with homology to Bowman-Birk proteinase inhibitors. AB - We have cloned and sequenced a wound-inducible cDNA clone designated WIP1 (for wound-induced protein) from maize coleoptiles. It was isolated by differential screening of a cDNA library prepared from excised maize coleoptile segments. The deduced amino acid sequence predicts a secretory, cysteine-rich protein of 102 residues with a calculated molecular mass of 11 kDa and a typical N-terminal signal sequence. The protein has about 30% identity with various Bowman-Birk type proteinase inhibitors. Most interestingly, it is novel in that it is double headed with exclusive specificity for chymotrypsin. WIP1 is strongly wound induced in contrast to other members of the Bowman-Birk proteinase inhibitor family, which occur in seeds and are regulated during development. The response is fast, similar to defence-induced genes, and measurable as early as 30 min after wounding. Induction can also be evoked in the intact coleoptiles and the signal is systematically transmitted in the coleoptile to adjacent regions of the wounded area. Isolation and analysis of the corresponding genomic clone reveals that WIP1 contains an intron of 90 nucleotides. PMID- 8358031 TI - The U6 small nuclear RNA gene family of potato. AB - Using the inverse polymerase chain reaction (IPCR), 19 U6snRNA gene promoters were isolated from the potato genome. Analysis of their nucleotide sequences revealed the existence of two subfamilies. Promoters from class 1 harbour the typical sequence elements required for plant snRNA gene transcription whereas those from class 2 do not have a TATA box. Three promoters were fused to a modified U6snRNA-coding sequence to allow their activity to be monitored in tobacco protoplasts. Two of the promoters, one from either class, were found to be active. Comparison of potato U6snRNA gene promoter sequences with those found in other plant species showed various degrees of homology. In addition, the entire nucleotide sequences of seven potato U6snRNA genes and one pseudogene were determined. The overall frequency of nucleotide changes after PCR was found to be 1.15 x 10(-3). The mutations appeared to be clustered in a distinct area and were all A-to-G/T-to-C substitutions. PMID- 8358032 TI - Purification and characterization of (1-->3, 1-->4)-beta-glucan endohydrolases from germinated wheat (Triticum aestivum). AB - A (1-->3, 1-->4)-beta-glucan 4-glucanohydrolase [(1-->3, 1-->4)-beta-glucanase, EC 3.2.1.73] was purified to homogeneity from extracts of germinated wheat grain. The enzyme, which was identified as an endohydrolase on the basis of oligosaccharide products released from a (1-->3, 1-->4)-beta-glucan substrate, has an apparent pI of 8.2 and an apparent molecular mass of 30 kDa. Western blot analyses with specific monoclonal antibodies indicated that the enzyme is related to (1-->3, 1-->4)-beta-glucanase isoenzyme EI from barley. The complete primary structure of the wheat (1-->3, 1-->4)-beta-glucanase has been deduced from nucleotide sequence analysis of cDNAs isolated from a library prepared using poly(A)+ RNA from gibberellic acid-treated wheat aleurone layers. One cDNA, designated lambda LW2, is 1426 nucleotide pairs in length and encodes a 306 amino acid enzyme, together with a NH2-terminal signal peptide of 28 amino acid residues. The mature polypeptide encoded by this cDNA has a molecular mass of 32,085 and a predicted pI of 8.1. The other cDNA, designated lambda LW1, carries a 109 nucleotide pair sequence at its 5' end that is characteristic of plant introns and therefore appears to have been synthesized from an incompletely processed mRNA. Comparison of the coding and 3'-untranslated regions of the two cDNAs reveals 31 nucleotide substitutions, but none of these result in amino acid substitutions. Thus, the cDNAs encode enzymes with identical primary structures, but their corresponding mRNAs may have originated from homeologous chromosomes in the hexaploid wheat genome. PMID- 8358033 TI - Upstream regulatory sequences from two beta-conglycinin genes. AB - Genes encoding the beta-conglycinin seed storage proteins of soybean are expressed only in seeds during specific stages of development. The different subunits of beta-conglycinin, alpha', alpha and beta, are encoded by distinct members of a gene family. Yet there are marked differences in the regulation of the genes encoding the alpha'/alpha and beta subunits. Previous work (Chen et al., EMBO J 7: 297-302, 1988) identified a seed specific transcriptional enhancer upstream of a gene encoding the alpha' subunit. Mutations were made within this region to discern its functional components. Among those identified is a 62 bp region (between -77 and -140) that contains a vicilin box consensus sequence as well as a sequence that binds the soybean nuclear factor SEF4 in vitro. A second region, which contains a sequence homologous to the core of the legumin box consensus (i.e., CATGCAT-like or RY repeat element) at -246, was also shown to affect the activity of this enhancer in transgenic plants. A series of 5' terminal deletions were used to identify regulatory elements upstream of the beta subunit gene. Two regions were identified (from -553 to -442 and from -308 to 72) that, when deleted, led to a marked reduction in gene expression. Both of these elements contain sequences that bind SEF4 in vitro. The distal element also contains an AT-rich segment that recognizes a second nuclear factor, SEF1, in vitro. Neither of these elements contains any homology to the vicilin box consensus. PMID- 8358034 TI - Structure of the intergenic spacer region from the ribosomal RNA gene family of white spruce (Picea glauca). AB - Five genomic clones containing ribosomal DNA repeats from the gymnosperm white spruce (Picea glauca) have been isolated and characterized by restriction enzyme analysis. No nucleotide variation or length variation was detected within the region encoding the ribosomal RNAs. Four clones which contained the intergenic spacer (IGS) region from different rDNA repeats were further characterized to reveal the sub-repeat structure within the IGS. The sub-repeats were unusually long, ranging from 540 to 990 bp but in all other respects the structure of the IGS was very similar to the organization of the IGS from wheat, Drosophila and Xenopus. PMID- 8358036 TI - A chimaeric tryptophan decarboxylase gene as a novel selectable marker in plant cells. AB - A novel selection system for plant genetic transformation was developed based on the enzyme tryptophan decarboxylase (TDC; EC 4.1.1.28) from Catharanthus roseus. This enzyme converts the toxic tryptophan analogue 4-methyl tryptophan (4-mT) into the non-toxic compound 4-methyl tryptamine. Expression of tdc in transgenic plants that have no endogenous TDC-activity allows selection on 4-mT. A vector was constructed containing a tdc cDNA clone under control of the constitutively expressed cauliflower mosaic virus 35S promoter. This vector was used in Agrobacterium-mediated tobacco leaf disc transformation experiments. The optimal concentration for selection with 4-mT was found to be 0.1 mM. The transformed nature of shoots obtained after tdc gene transfer and subsequent selection on 0.1 mM 4-mT was confirmed by northern blot analysis. PMID- 8358035 TI - The petunia homologue of the Antirrhinum majus candi and Zea mays A2 flavonoid genes; homology to flavanone 3-hydroxylase and ethylene-forming enzyme. AB - The synthesis of anthocyanins in higher plants involves many enzymatic steps. Here we describe the isolation and characterization of a cDNA, ant17, which encodes a protein that has 73% amino acid sequence identity with the candi gene product of Antirrhinum majus and 48% with that of the maize a2 gene. This protein may therefore be involved in the synthesis of anthocyanins in the steps after the action of dihydroflavonol 4-reductase. This is consistent with the absence of ant17 expression in the regulatory anthocyanin mutants of petunia an1, an2 and an11. Furthermore, ant17 is predominantly expressed in corollas and anthers and is induced by gibberellic acid. PMID- 8358037 TI - A highly conserved alpha-tubulin sequence from Prunus amygdalus. AB - The sequence of an alpha-tubulin from Prunus amygdalus has been obtained by cDNA cloning. When this sequence is compared to that of the Tub alpha 1 gene from maize it shows a very high degree of similarity, much higher than any of the alpha-tubulin sequences reported so far from plants. The expression of this gene is high in the stages of seed development where a high divisional activity is present. It is preferentially expressed in the radicular tissues as it is gene Tub alpha 1 in maize. Southern analysis indicates that this gene may form a subfamily of alpha-tubulin genes having similar sequence and tissue specificity and existing at least in maize and in Prunus. PMID- 8358038 TI - cDNA cloning and expression of a potato (Solanum tuberosum) invertase. AB - A cDNA clone encoding an invertase isoenzyme has been isolated from a potato leaf cDNA library. The deduced amino acid sequence shows significant similarities to previously characterised invertases. The highest degree of overall similarity, including the signal peptide sequence, is to carrot cell wall invertase, suggesting that the potato gene encodes an apoplastic enzyme. Expression of the gene, as determined by RT-PCR, is detected in stem and leaf tissue, and at lower levels in tuber, but is absent from roots. PMID- 8358039 TI - In planta analysis of the Agrobacterium tumefaciens T-cyt gene promoter: identification of an upstream region essential for promoter activity in leaf, stem and root cells of transgenic tobacco. AB - The promoter region of the Agrobacterium tumefaciens T-cyt gene was fused to a beta-glucuronidase (gusA) reporter gene and introduced into tobacco plants. Detection of gusA expression in transgenic F1 progeny revealed that the T-cyt promoter is active in many, if not all, cell types in leaves, stems and roots of fully developed plants. Developmental stage-dependent promoter activity was observed in seedlings. Analysis of 5'-deleted promoter fragments showed that sequences located between positions -185 and -139 with respect to the T-cyt translational start codon are essential for T-cyt promoter activity in transfected tobacco protoplasts as well as in transformed tobacco plants. PMID- 8358040 TI - Comparative sequence analysis of cis elements present in Glycine max L. leghemoglobin lba and lbc3 genes. AB - The soybean leghemoglobin lba gene promoter sequence was determined and aligned with the promoter sequence of the soybean lbc3 gene from the same gene family. Five highly conserved regions were found. There are two large conserved regions, one of which overlaps the basic promoter while the other defines a minimal enhancer in the upstream positive elements. Within the minimal enhancer, an inverted repeat with similarity to the binding site of a yeast transcription factor, GCN4, was found. This particular repeat is conserved in the promoters of all functional soybean lb genes as well as in lb gene promoters from other legumes. This suggests that the inverted repeat is important for leghemoglobin gene expression. PMID- 8358041 TI - Detection of partial deletion and partial duplication of dystrophin gene in Japanese patients with Duchenne or Becker muscular dystrophy. AB - The dystrophin gene was analyzed in 59 Japanese patients with Duchenne muscular dystrophy (DMD) from 48 unrelated families, including 11 pairs of siblings, and three patients with Becker muscular dystrophy (BMD) from two unrelated families, including one pair of siblings. The relationship between the type of gene abnormality and clinical symptoms was examined. Twenty-seven of 50 (54.0%) unrelated DMD or BMD patients were found to have partial deletions, and five (10%) appeared to have partial duplications in the dystrophin gene. Nine DMD patients, including three pairs of siblings, showed mental retardation, the existence of which was coincident in each pair of siblings, but deletion of an identical exon was not always related to mental retardation in unrelated patients. PMID- 8358043 TI - PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western Japan. AB - An alpha 1-antitrypsin deficiency associated with pulmonary emphysema was investigated in a 32-year-old Japanese male. Polymerase chain reaction (PCR) amplified fragments and dot blot hybridization with allele-specific oligonucleotide probes revealed that the patient was homozygous for a C to T transition at codon 53, resulting in the substitution of Phe53 for Ser53 (PI*S(iiyama)). Crossed immunoelectrophoresis after isoelectric focusing and agarose gel electrophoresis showed atypical banding patterns. PI*S(iiyama) is a rare deficiency gene, but it can occur sporadically all over the Japan. PMID- 8358042 TI - Deletion detection for diagnosis of Duchenne muscular dystrophy in the Japanese population--comparison between the polymerase chain reaction and the Southern blot analysis. AB - We compared the efficacy of the multiplex PCR with that of the cDNA analysis for detection of deletions of the DMD gene in the Japanese patients. Thirty males with DMD from 27 Japanese families were studied by the multiplex PCR, and 24 of them were also investigated by Southern blot analysis. We used five dystrophin cDNA probes for deletion analysis. A total of 19 regions were amplified by the PCR to detect deletions, 9 regions by the method of Chamberlain et al. and another 10 regions by the method of Beggs et al. Deletions were detected in 14 (52%) out of 27 DMD families by the PCR. Southern blot analysis detected deletions in 14 (64%) out of 22 families. Thirteen (93%) of the 14 DMD families with deletions detected by Southern blotting were also confirmed by the multiplex PCR. Provided care is taken in cases where the deletion is limited to a single exon, the multiplex PCR appears to be an efficient and useful alternative to conventional Southern blot analysis for detecting deletions during the prenatal and postnatal diagnosis of DMD. PMID- 8358044 TI - Two Japanese cases with microcephalic primordial dwarfism: classical Seckel syndrome and osteodysplastic primordial dwarfism type II. AB - A male infant with "classical" Seckel syndrome and a girl with osteodysplastic primordial dwarfism type II are described. The boy with classical Seckel syndrome had severe brain dysplasia, a finding hitherto unreported in patients with this syndrome. The patient with osteodysplastic dwarfism type II had skeletal abnormalities including lumbar scoliosis, a small and high pelvis, metaphyseal flaring of the distal radii and ulnae, V-shaped metaphyseal flaring of the distal femorae, and short metacarpals and phalanges. The mother of this girl was short, microcephalic, and had disproportionately short forearms and legs. In view of this, dominant inheritance of the disease was suggested. PMID- 8358045 TI - Interstitial deletion of the long arm of chromosome 11 determined by fluorescence in situ hybridization. AB - An interstitial deletion, del(11)(q14q22), found in a female infant was examined by fluorescence in situ hybridization with cosmid DNA markers mapped on the long arm of chromosome 11. Three cosmids mapped on 11q14.1-11q22.1 region were not hybridized to the del(11) chromosome, while all the other DNA markers mapped on 11cen-11q14.1 and 11q23.1-11qter region gave hybridization signals on the del(11) chromosome. Cytogenetic analysis after R-banding confirmed an apparent deletion of 11q14-q22, but containing a small R-negative band, a part of 11q22.3 and/or 11q14.1, in the middle part of del(11) chromosome. The karyotype thus was determined to be 46,XX,del(11)(q14.1q22.3). PMID- 8358046 TI - A case of Goldenhar syndrome associated with growth hormone deficiency. AB - We have experienced the case of a 10-year-old boy who had Goldenhar syndrome accompanied by growth hormone (GH) deficiency. His height increased after treatment with growth hormone was administered. We found no untoward effects of the hormone and we consider that treatment with GH is useful for patients who present with Goldenhar syndrome associated with growth hormone deficiency. PMID- 8358047 TI - A case of schizophrenia with a dicentric Y chromosome. AB - A case of DSM-III-R schizophrenia with a dicentric Y chromosome (46,X,dic(Y)(q11)) is reported. Structural chromosome abnormalities such as this case may provide clues to finding regions of the genome etiologically involved in schizophrenia. PMID- 8358048 TI - Effect and mechanism of sucralfate on healing of acetic acid-induced gastric ulcers in rats. AB - We examined the effect of sucralfate on spontaneous and delayed healing of experimental gastric ulcers and the underlying mechanism of action. Gastric ulcers were produced 5 days after submucosal injection of 20% acetic acid (0.03 ml) into the antral-oxyntic border of rat stomachs. To delay the healing of ulcers, indomethacin was administered s.c. at 1 mg/kg once daily for 4 weeks from 5 days after the acid injection. Sucralfate, administered p.o. three times daily, significantly accelerated the spontaneous healing of ulcers, the healing rates being 13.7%, 43.7% and 47.1% with 100 mg/kg, 300 mg/kg and 600 mg/kg, respectively. In addition, the drug also significantly prevented the delay in ulcer healing caused by indomethacin, the preventive rates being 56.6% and 83.9% with 300 mg/kg and 600 mg/kg, respectively. Sucralfate, even at 1000 mg/kg, had no effect on the mucosal prostaglandin E2 (PGE2) level around the ulcers and did not affect the reduced PGE2 content caused by indomethacin. A single dose of sucralfate significantly increased the volume and the pH of the gastric contents in a dose-dependent manner, the effects persisting for up to 8 hr. These results suggest that the mechanism by which sucralfate accelerates the healing of gastric ulcers is unrelated to endogenous PGs but related to the acid-neutralizing activity. PMID- 8358049 TI - Adenosine modulates reactive hyperemia in rat gut. AB - Intestinal reactive hyperemia is an abrupt blood flow increase following release from anterior mesenteric arterial occlusion. We investigated the role of adenosine in reactive hyperemia. In anesthetized rats, mesenteric arterial velocity of blood flow was determined with pulsed Doppler velocimetry and arterial pressure with a transducer. Three indices quantifying reactive hyperemias obtained following 30, 60, and 120 s arterial occlusions included duration, the volume of blood flow exceeding preocclusion blood flow, and the percentage increase in conductance. In six rat groups (half fasted and half with intrajejunal bile-oleate solutions), hyperemia parameters were determined before and after administration of either adenosine deaminase (ADA) or two adenosine receptor antagonists, namely 8-phenyltheophylline (8-PT) and 1,3-dipropyl-7 methylxanthine (DPMX). In fasted gut the three agents had variable effectiveness against reactive hyperemia, although 8-PT was the most consistent inhibitor. Instillation of intrajejunal lipid evoked a stable hyperemia and increased duration and blood flow volume after each occlusive period. ADA and 8-PT were more effective against reactive hyperemia in fed gut than in fasted gut. Our findings suggest that adenosine is a vasodilator metabolite modulating mesenteric reactive hyperemia, especially during enhanced intestinal metabolic activity. PMID- 8358050 TI - Microcirculatory and motor effects of endogenous nitric oxide in the rat gut. AB - The aim of the study was to determine the role of endogenous nitric oxide (NO) as the mediator of intestinal blood flow and motility. Experiments were performed on anesthetized rats. Blood flow in the jejunum was determined by Laser-Doppler flowmeter. Motility was monitored on the basis of changes in intrajejunal pressure. Systemic arterial pressure was also recorded. To investigate the potential role of nitric oxide in the regulation of basal intestinal blood flow and motility the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) was given systemically. Intravenous bolus of L-NNA (15 mg/kg) reduced basal intestinal blood flow and increased both intestinal motility and arterial pressure in the dose-dependent manner. To test the specificity of the NO synthase blockade we administered L-arginine alone or in combination with L-NNA. Pretreatment with L arginine (100.0 mg/kg i.v.) alone had no major influence but when combined with L NNA it reversed the intestinal circulatory and motor effects of L-NNA. The results of these studies suggest that endogenous NO exerts a tonic relaxatory influence on the smooth muscle of the intestinal vessels and intestinal wall. PMID- 8358051 TI - Inhibitory effects of indomethacin on growth and proliferation of gastric carcinoma cells KATO III. AB - The effects of indomethacin on growth and proliferation of gastric carcinoma cells KATO III were examined. Indomethacin (10(-4) and 10(-3) M) significantly inhibited cell growth and these effects were not affected by treatment with 16,16 dimethyl prostaglandin E2 (3 x 10(-7) M and 3 x 10(-6) M). Indomethacin 10(-3) M significantly reduced cell viability and completely inhibited cell growth. Indomethacin 10(-4) M did not affect cell viability and its inhibitory effect of cell growth became apparent on the fifth day of culture. Indomethacin 10(-4) M reduced BrdU labeling index within 2 hours. These results suggest that indomethacin inhibited growth and proliferation of gastric carcinoma cells KATO III. This effect is not mediated by prostaglandins. PMID- 8358052 TI - Insulin-like immunoreactivity (IRI) in the rat hypothalamo-neurohypophysial system: effect of dehydration and haemorrhage. AB - Hypothalamic IRI was not affected in haemorrhaged rats, but diminished considerably in the dehydrated ones. In the neurohypohysis, IRI was distinctly higher both in dehydrated and haemorrhaged rats, i.e., under disorders which stimulated vasopressin and/or oxytocin release. It is suggested that insulin-like substance(s) may be someway involved in regulation of vasopressin or oxytocin secretion. PMID- 8358053 TI - Kinins and thrombolysis. AB - In cats with extracorporeal circulation arterial blood pressure and thrombolysis were assayed. In this model apart from their hypotensive properties kallikrein (3 10 units/kg, i.v.) and captopril (> 200 micrograms/kg, i.v.) dissipated blood clots which were preformed on superfused collagen strips. Captopril at a lower dose of 50 micrograms/kg i.v. potentiated the thrombolytic effect of kallikrein while aprotinin (100,000 unit/kg, i.v.) abolished it. Thrombolysis by kallikrein was mediated by an unstable principle which was decomposed by blood during 15 min of incubation at 37 degrees C. Generation of this principle was inhibited by pretreatment of animals with aspirin (50 mg/kg, i.v.). The above analysis points to prostacyclin which owing to its platelet-suppressant and fibrinolytic properties induces thrombolysis when released by kinins. PMID- 8358054 TI - Effect of thyrotropin on phospholipid composition in thyroid plasma membranes. AB - Differences particular in phospholipid levels from pig thyroid membranes incubated in the presence of TSH were observed, but with exception of lysophosphatidylcholine, were not statistically significant. TSH evoked about a twice increase of lysophosphatidylcholine content. A slight decrease of phosphatidylcholine, phosphatidylinositol and phosphatidylserine were found, when at the same time a slight increase of phosphatidylethanolamine and sphingomyelin level was noted. There were no statistical differences in range fluctuation of individual phospholipid levels, but direction of fluctuation (i.e. decrease or increase) were identical for every single phospholipid in all experiments. An increase of lysophosphatidylcholine and a simultaneously decrease of phosphatidylcholine contents suggests the stimulation of phospholipase A2 activity. PMID- 8358055 TI - Actions and interactions of endothelins, prostacyclin and nitric oxide in the gastric mucosa. AB - The modulation of the gastric mucosal microcirculation plays a key role in the maintenance of gastric integrity. Disruption of the balance between the local release of vasodilator and vasoconstrictor mediators could therefore be involved in the pathogenesis of mucosal injury. Thus, the endothelium derived peptide endothelin-1 (ET-1), induces mucosal injury following local administration. In contrast, the vasodilator prostanoids, prostacyclin and PGE2 can protect against gastric damage, while inhibition of endogenous prostanoid formation by cyclo oxygenase inhibitors augment mucosal damage, including that induced by ET-1. Sensory neuropeptides such as calcitonin gene-related peptide (CGRP) may also play a local protective role, since acute intragastric administration of capsaicin which stimulates neuropeptide release, protects against mucosal injury induced by ET-1, as does local infusion of CGRP. Furthermore, chronic administration of capsaicin which deplete primary sensory neurones augments gastric damage induced by a number of ulcerogens including ET-1. Nitric oxide (NO) synthesized from L-arginine can regulate gastric mucosal blood flow, both under resting conditions and following stimulation of acid secretion. Inhibition of NO biosynthesis alone does not induce acute mucosal injury, yet extensive haemorrhagic damage results from concurrent inhibition of NO formation, cyclo oxygenase inhibition and depletion of sensory neuropeptides. NO donors can protect against ulceration, although the unregulated release of high levels of NO can lead to mucosal injury. Thus, NO has a critical interactive role with other local protective mediators such as the prostanoids and sensory neuropeptides in the physiological regulation of mucosal integrity. PMID- 8358056 TI - Chemotherapy in esophageal cancer. AB - Esophageal cancer is a virulent malignancy, with the conventional approach of surgery or radiation therapy offering patients only a small chance for long-term disease-free survival. The frequent early systemic dissemination of disease has prompted an ongoing interest in the study of chemotherapy. A broad range of antitumor agents have been studied which demonstrate moderate antitumor activity. A number of combination chemotherapy regimens, mainly cisplatin-based, have been studied, which have consistently greater antitumor activity in local regional disease compared with metastatic disease. The use of preoperative chemotherapy in the surgical treatment of the disease remains investigational. Results from clinical trials comparing radiation therapy alone with concurrent radiation and chemotherapy demonstrate a survival benefit for the use of a combination of concurrent chemotherapy and radiation compared to radiation therapy alone. However, current studies with conventional chemotherapy, radiation and surgery are likely to impart at best a modest to moderate improvement in the treatment of esophageal carcinoma. The priority in chemotherapy trials, therefore, remains the identification of new active chemotherapy agents. The search for novel therapeutic approaches, exploiting advances in understanding of the molecular biology of the disease, continues. PMID- 8358057 TI - Update of hormonal treatment in cancer of the prostate. AB - Prostate carcinomas are heterogeneous tumors composed of hormone sensitive and hormone insensitive cells. Although all androgens have an effect on prostatic cells, it is believed that dihydrotestosterone (DHT) is the active metabolite primarily utilized by prostatic cancer cells for growth and division. Hormonal therapies are therefore designed to lower tissue levels of DHT or prevent its binding to receptors on prostatic cancer cells. The Veterans Administration Cooperative studies in the 1960s and 1970s laid the groundwork for the use and timing of hormonal therapy. Until recently orchiectomy and estrogens were the two main alternatives, but new compounds such as luteinizing hormone releasing hormone analogs and antiandrogens have shown to be as effective and less toxic than estrogens. Today, important controversies concerning the selection of the best primary treatment and the timing of initiating the hormonal therapy still exist. Second line hormonal strategies are used, but they still have to prove their impact on overall survival. PMID- 8358058 TI - Transient hyperammonemia related to chemotherapy with continuous infusion of high dose 5-fluorouracil. AB - Hyperammonemic encephalopathy has been reported in patients receiving chemotherapy (CT). It is characterized by abrupt alteration in mental status with markedly elevated plasma ammonium levels in the absence of obvious liver disease. This paper reports seven patients who developed transient hyperammonemia during chemotherapy. The regimens all included continuous infusion of high-dose 5 fluorouracil (5-FU). The onset of hyperammonemic encephalopathy was 1.5-4 days after the start of CT. Five cases had infection and six had prerenal azotemia at the time of hyperammonemia. After management, plasma ammonium levels all returned to the normal range within 2 days. Except for one persistent coma, status of consciousness cleared completely. The true mechanism of transient hyperammonemia is unclear. The excess production of ammonium due to metabolites of 5-FU added to precipitating factors such as infection, hypovolemia or constipation may be the explanation for transient hyperammonemia in our study. PMID- 8358059 TI - Epidoxorubicin and high dose leucovorin plus 5-fluorouracil in advanced gastric cancer: a phase II study. AB - We conducted a multicentric phase II study on advanced gastric cancer to determine the efficacy and toxicity of treatment with epidoxorubicin (EPI) plus high doses of leucovorin (LV) and 5-fluorouracil (5-FU). Thirty-seven patients with measurable disease were enrolled into the trial and treated with EPI 75 mg/m2 on day 1 and LV 200 mg/m2 plus 5-FU 450 mg/m2 from day 1 to 3, the cycle being repeated every 3-4 weeks from a median of five cycles per patients. The response rate was 49% in 35 evaluable patients, with two complete remissions and 15 partial responses. Median response duration was 12.4 months; median survival for responding patients was 17.3 months, which was significantly longer than 8.7 months for non-responding patients. General toxicity was usually mild, myelotoxicity was moderate and there was no evidence of cardiac toxicity. These results show that EPI-LV-5-FU is an effective regimen for advanced gastric carcinoma. The efficacy of this combination should now be tested as an adjuvant therapy in resectable gastric cancer. PMID- 8358060 TI - Metastatic adenocarcinoma of the endometrium treated with 13-cis-retinoic acid plus interferon-alpha. AB - Phase II trials of the novel biologic combination of 13-cis-retinoic acid plus interferon (IFN)-alpha have achieved major activity in advanced squamous cell carcinomas of the skin and cervix, but not of the lung or head and neck. Very limited study of this combination has occurred in cancers other than those of squamous type. Although uncommon, cases of unresectable or metastatic endometrial adenocarcinoma are virtually incurable, and chemotherapy has had no impact on survival in these cases. This report describes our use of 13-cis-retinoic acid plus IFN-alpha to treat a case of cisplatin- and hormone-resistant, locally advanced and distantly metastatic adenocarcinoma of the endometrium. In this worst-prognosis case, the biologic therapy achieved a major response, which persisted for 4 months. Based on the dramatic activity in this case, we believe that depthful mechanistic and clinical study of this promising new biologic combination should be expanded to include non-squamous tumors of many different sites and histopathologic types. PMID- 8358062 TI - Decrease in vivo of cysteine endopeptidases in blood of patients with tumor of the larynx. AB - Since cysteine endopeptidase (cathepsins B and L) have been proposed to be implicated in tumor malignancy, we have attempted to decrease these in vivo. Large amounts of urine cysteine peptidase inhibitors (UCPI) are present in the urine of patients. Our results indicate protective effects of a UCIP preparation against human serum cysteine endopeptidases. PMID- 8358061 TI - Effective salvage therapy using all-trans retinoic acid for relapsed and resistant acute promyelocytic leukemia. AB - All-trans retinoic acid (ATRA) has been shown to be active against acute promyelocytic leukemia (APL). Six patients with APL, either in relapse or resistant to initial chemotherapy were reinduced with ATRA 100 g/m2/day for 6 weeks. Complete remission was achieved in all six of them. Side effects were seen in two of them. ATRA appears to provide a relatively safe and reliable means to induce a complete remission in patients with refractory or relapsed APL. PMID- 8358063 TI - Polyamine increase in rat tissues treated with 1-beta-D-arabinosylcytosine and 5 fluorouracil. AB - The effects of 1-beta-D-arabinosylcytosine (ara-C) and 5-fluorouracil (5-FU) on body weight, and the contents of putrescine, spermidine and spermine in 14 different tissues were examined in rats given these drugs for 5 days. There were statistically significant increases in all three polyamines in the small intestine, in spermidine in the lung, and in spermine in the thymus, spleen and liver of rats treated with ara-C and 5-FU. Putrescine content in the spleen, heart, muscle and liver, and spermidine and spermine contents in the stomach of the 5-FU-treated rats also showed significant increases. PMID- 8358064 TI - AS-101: a modulator of in vitro T-cell proliferation. AB - AS-101 is a tellurate compound originally designed as a drug with cytostatic activity. Nevertheless, in vivo it was found to be an immunomodulator agent due to a stimulation of cytokine production. Mitotic Index (MI) as an indicator of cytotoxicity and cell proliferation kinetics (CPK) in lymphocytes cultures are parameters used in the evaluation of the antineoplastic activity of drugs, such as mitomycin-C and cisplatin. For this reason, we evaluated the effects of AS-101 upon these two parameters. The results show that AS-101 produces an inhibition of MI in proliferating lymphocytes higher than the inhibition mediated by cisplatin. When CPK was evaluated, AS-101 induced a retardation not related with dose, while cisplatin produced a stepwise inhibition. This effect contrasts with the stimulation observed when AS-101 was added to non-proliferating lymphocytes which was measured as an increased [3H]thymidine incorporation in culture. The results confirm the mode of action of AS-101 as a real modulating agent of cell proliferation. PMID- 8358065 TI - In vitro cytotoxic activity of 1-alkylpiperidine N-oxides and quantitative structure-activity relationships. AB - The main objective of the present investigation was to screen a series of 1 alkylpiperidine N-oxides for in vitro cytotoxicity, and to find out whether there is a quantitative structure-activity correlation (QSAR) between cytotoxic effect represented here by inhibition of incorporation of [14C]adenine into nucleic acid or [14C]valine into proteins in Ehrlich ascites carcinoma (EAC) cells and structure (as a structural parameter the number of carbon atoms m in the alkyl chain was used). On the basis of primary screening, one of the most active compounds, i.e. 1-decylpiperidine N-oxide, was chosen for further biochemical study. The drug inhibited the incorporation rate of 14C-labeled precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of Ehrlich cells, the extent of inhibition being dependent on both time and concentration of the compound in the incubation medium. The lengthening of the alkyl chain in 1 alkylpiperidine N-oxides positively affected their cytotoxic activity in Ehrlich cells. For these compounds the optimal m value is 12-15. PMID- 8358066 TI - Ethyl 4-isothiocyanatobutanoate--antiproliferative activity in vitro and in vivo. AB - A new isothiocyanate (ITC) derivate ethyl 4-isothiocyanatobutanoate (E-4IB) induces an immediate dose-dependent inhibitory action on the division of HeLa cells in the concentration range 1.0-0.1 mg/l. Concomitant with the decrease in cell proliferation which follows E-4IB treatment the protein:cell number ratio increases and DNA accumulates. Cells which have lost their ability to divide do not stop their glucose metabolism and only partly stop their glutamine metabolism. The increased content of DNA suggests that cells synthesize DNA without entering into mitosis and that dying cells are in late S or G2 phases prior to death. E-4IB produces a significant growth inhibition of transplanted sarcoma cells B77-RF in rats (at 28 mg/kg). A 57% regression in tumor volume was observed for at least 30 days following the completion of the in vivo treatment. These findings support the presumption that E-4IB is a potential anti-cancer drug. However, further studies are needed for the optimization of its in vivo activity. PMID- 8358067 TI - Enhancement of LAK-like activity and cytokine induction in regional lymph nodes and spleen cells of mice after intralymphnodal injection of OK-432, a killed streptococcal preparation. AB - A single dose of inactivated streptococci (OK-432) was injected into the popliteal lymph nodes of male CDF1 mice and its effects on popliteal, inguinal, and para-aortic lymph node cells and spleen cells were investigated and compared with the effects of subcutaneous injections of the same dosage of OK-432. Regional lymph node cells and spleen cells obtained from intralymphnodally injected mice lysed not only natural killer (NK)-sensitive YAC-1 cells, but also NK-resistant P-815 and meth-A cells. Lysis of target cells was inhibited when effector cells were treated with anti-Thy-1.2 or anti-Lyt-2.2 monoclonal antibody and complement, but no inhibition was apparent after treatment with anti-asialo GM1 or anti-Lyt-1.2 antibody and complement. These results suggest that the effector cells are lymphocyte-activated killer (LAK) cells. An enhanced capacity of lymph node cells to produce cytokines, tumor necrosis factor and interleukin 1 upon restimulation with lipopolysaccharide was found only in intralymphnodally injected mice. Thus, the induction of LAK-like cells and cytokine production in regional lymph nodes and spleen cells by the intralymphnodal administration of OK 432 should be effective for the inhibition or treatment of lymph node metastases. PMID- 8358068 TI - The cytotoxicity of N-substituted indazolones in murine and human tumor cells. AB - N-Substituted indazolones are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt3, colon adenocarcinoma and HeLa S3. Selected agents were also active against the growth of KB, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of L1210 cells, which reduces DNA and RNA syntheses. Agents lowered d(NTP) pools, further reducing DNA synthesis. DNA strand scission was evident after incubation with N-substituted indazolones for 24 h at 100 microM, lowering DNA synthesis and causing cell death. PMID- 8358069 TI - Rhein inhibits glucose uptake in Ehrlich ascites tumor cells by alteration of membrane-associated functions. AB - Rhein (RH), 4,5 dihydroxyanthraquinone-2-carboxylic acid, is known to inhibit the glycolysis of neoplastic cells by impairing glucose uptake. In order to establish whether this might be due to a selective interaction of the carrier with the drug or to functional modifications of the cell membrane, the effect of RH on glucose uptake in Ehrlich ascites tumor cells has been investigated. RH strongly inhibits the uptake of both 2-deoxyglucose and 3-O-methylglucose, so the reduced influx therefore cannot be ascribed to an effect on glucose phosphorylation. The inhibition of glucose transport does not depend on a reduction of the number of the carriers as indicated by the inability of the drug to interfere with the synthesis of the transporter. Moreover, the extent of total binding of cytochalasin B, as well as the fact that glucose specificity is not altered, indicate that the intrinsic activity of the glucose carrier is not affected. We therefore conclude that the inhibition of glucose uptake must be ascribed to an interaction of the drug with cell membranes that results in an alteration of membrane-associated functions. PMID- 8358070 TI - Neosurugatoxin blocks an alpha-bungarotoxin-sensitive neuronal nicotinic acetylcholine receptor. AB - Neosurugatoxin (NSTX), a neurotoxin isolated from the Japanese ivory mollusc Babylonia japonica, is a potent neuronal nicotinic acetylcholine receptor (nAChR) antagonist. Hitherto, NSTX has been found to block only neuronal nAChRs that are insensitive to alpha-Bgt. Here, we report for the first time that NSTX blocks an alpha-Bgt-sensitive nAChR on an identified insect motor neurone. Bath-applied NSTX at a concentration of 10 nM and above reversibly blocks the nicotine-induced depolarizations recorded from the cockroach (Periplaneta americana) fast coxal depressor motor neurone (Df) and is without effect on GABA-induced responses detected on the same cell. NSTX is among the most potent blockers tested to date on nAChRs of motor neurone Df. PMID- 8358071 TI - Defense mechanisms in insects: certain integumental proteins and tyrosinase are responsible for nonself-recognition and immobilization of Escherichia coli in the cuticle of developing Ceratitis capitata. AB - A defense mechanism in the cuticle of developing C. capitata was demonstrated using an in vitro system consisting of isolated cuticular tyrosinase from C. capitata, cuticular tyrosinase-free proteins, tyrosine, and E. coli. The simultaneous presence of the above components resulted in the formation of large immobilized E. coli aggregates. By contrast, omission of any of the above components failed to produce such aggregates. In other words, E. coli retained their mobility and viability. The results indicate that certain cuticular proteins are responsible for the nonself-recognition, since they are able to bind to the E. coli surface in vitro, and a reactive tyrosine derivative is generated by the action of cuticular tyrosinase for the immobilization and probably killing of E. coli. Based on these studies the most likely explanation for the nonself recognition and immobilization and/or killing of bacteria is the production of E. coli-protein complexes and their crosslinking through quinone intermediate. PMID- 8358072 TI - On the control of ecdysone biosynthesis by the central nervous system of blowfly larvae. AB - Ecdysone was found to be the major secreted steroid of ring glands dissected from blowfly larvae and incubated in vitro. Other secretory products such as 3 dehydroecdysone and 20-deoxy-makisterone A could not be detected when the glands were labelled with tritiated cholesterol. Ecdysone synthesis and secretion were found to be tightly coupled. The highest rate of secretion was observed a few hours before pupariation. In vitro, the rate of ecdysone secretion by ring glands was affected significantly by coincubation with the central nervous system (CNS). Modulating effects from the CNS to the gland were mediated both by culture medium and by nerve connections. Distinct parts of the CNS revealed multiple and partially opposite effects on ecdysone secretion, suggesting a more complex control than had been anticipated. Multiple neural control systems appear to be involved. Moreover, the observed effects changed with development during the second half of the third instar, reflecting a significant plasticity of neural control. PMID- 8358073 TI - Bacterial translocation and reticuloendothelial function after implantation of abdominal drainage in the rat. AB - Bacterial translocation and reticuloendothelial system (RES) function were measured in the rat after intraperitoneal (IP) implantation of rubber drain pieces (7.5 cm2). Six hours after implantation, enteric bacterial translocation was noted to mesenteric lymph nodes (MLNs), the liver, spleen, lungs, kidneys and portal and caval vein blood. RES function was evaluated in terms of blood clearance and organ uptake of intravenously injected 125I-labelled, heat-killed E. coli. A significant elevation of corrected phagocytic index (alpha) was found 24 hours after IP implantation. Localization of 125I-labeled E. coli was significantly enhanced in systemic organs (kidneys, spleen, liver and lungs) 24 hours after IP implantation, whereas it was locally impaired (MLNs and proximal jejunum) 6 hours after IP implantation and thereafter. An inverse correlation between the localization of radiolabelled E. coli in the liver, spleen and lungs and the incidence of bacterial translocation to these organs was found. The results suggest that an association exists between alterations in RES function and bacterial translocation in the early course following IP implantation of rubber drains. PMID- 8358074 TI - Oesophageal cancer in gastric surgery patients. AB - Oesophageal adenocarcinoma (which has been steadily increasing in incidence during the last 20 years) is thought to be promoted by gastric reflux. In a cohort of 5018 gastric surgery patients, 19 of whom developed oesophageal cancer, there was no increased proportion of adenocarcinomas. We conclude that the hypothesized aetiology was not supported. PMID- 8358075 TI - A randomized controlled trial of a new PEG-electrolyte solution compared with a standard preparation for colonoscopy. AB - The efficacy, tolerability and patient acceptance of a new flavoured PEG solution for gut lavage was compared with a standard preparation for bowel cleansing in a randomized controlled trial of patients undergoing colonoscopy. One hundred and sixty patients were randomly allocated either to a standard preparation (2-day semi-liquid diet, laxatives and cleansing enemas) or to gut lavage (fractionalized ingestion of lavage solution, two litres in the afternoon before and a third litre the morning of the examination). Adequacy of colon cleansing was scored evaluating residual stool in each colonic segment and overall mucosal visibility. Tolerability of methods was assessed by evaluating the incidence and severity of side-effects. Patient acceptance was graded (good, fair to good, poor) according to the patient's judgement about the ease of execution and interference with sleep and working activity. Less residual stool (p < 0.05) and better visualization of colonic mucosa (p < 0.05) were obtained with gut lavage than with standard preparation. Both methods were well-tolerated and a low incidence of side effects was recorded in both groups. Patient acceptance was good in more than 80% of patients in both groups. We conclude that gut lavage is a rapid, effective and well-tolerated method for bowel cleansing. The use of a flavoured solution in a fractionalized schedule seems to improve the tolerability and the patient acceptance of this method. PMID- 8358076 TI - Characterization of agarose as an encapsulation medium for particulate specimens for transmission electron microscopy. AB - Agarose, agar, and gelatin were initially compared as encapsulation media for 3 structurally diverse particulate specimens: bacteria, yeast, and mitochondria. Agarose proved superior to both gelatin and agar for ease of handling and overall image quality (minimum background). All sample types exhibited high quality fixation and structural detail with no heat damage from the agarose medium. Based on this finding, we further characterized agarose encapsulation as affected by post-fixation, en bloc staining and resin type. Osmium tetroxide post-fixation, followed by en bloc uranyl acetate staining, could be performed without an increase in the electron density of the encapsulation medium. Agarose proved successful as an encapsulation medium regardless of the resin type or preparation protocol, thus providing flexibility in experimental design and excellent results over a range of variables. PMID- 8358077 TI - Subcellular calcium localization in Toxoplasma gondii by electron microscopy and by X-ray and electron energy loss spectroscopies. AB - The localization of calcium in Toxoplasma gondii tachyzoites was studied at the ultrastructural level, with a cytochemical pyroantimonate precipitation method (PA) and controlled by EGTA chelating and EDX and EELS microanalyses. Appropriate conditions for material preparation, fixation and embedding, were defined. The proportion of precipitates that were either free or inside vacuoles and their distribution inside Toxoplasma appeared to be PA dose-dependent. Precipitation mainly occurred in the anterior pole of the Epon-embedded tachyzoites. EDX and EELS analyses showed that out of 30 PA precipitates inside tachyzoites, 78% contained Ca. In Melamine sections, 96% of the tachyzoites had intracellular precipitates and the membrane complex was stained; 25% of the tachyzoites inside host cells contained PA-Ca precipitates, but most of them were retained in the reticular network of the parasitophorous vacuole. Melamine embedding appeared to improve the preservation of calcium pyroantimonate precipitates. PMID- 8358078 TI - Rapid primary microwave-glutaraldehyde fixation preserves the plasma membrane and intracellular structures of the protozoan Tritrichomonas foetus. AB - Tritrichomonas foetus, a pathogenic protozoan, was used as a model to analyse microwave-stimulated fixation as a procedure of preparation of biological samples for electron microscopy of thin sections and freeze-fracture replicas. Good preservation of the protozoan structure was achieved by microwave-stimulated fixation and Epon polymerization. The membrane structure, as visualized in freeze fracture replicas, was well preserved. PMID- 8358079 TI - Selective etching of AlAs for preparation of III-V semiconductor thin foils. AB - A new method of thin section preparation of III-V semiconductors and multilayers for transmission electron microscopy (TEM) is presented that exhibits considerable advantages over conventional methods such as ion beam milling and jet thinning. GaAs thin films and multilayers of GaAs/In chi Ga1-chi As/GaAs are grown over an etch release layer of AlAs on GaAs substrates by molecular beam epitaxy (MBE). Planar TEM sections prepared by selective etching from these samples show improved ability to image film morphology and dislocation arrangements, and the resulting large thin electron transparent areas facilitate dislocation density measurements and detection of spatial variations. Avoidance of radiation effects and wedge shaping, both common to ion milled samples, allows this method to be used to prepare uniform thickness standards of single layer GaAs films for EDS analysis or lattice imaging. PMID- 8358080 TI - High resolution and image processing of otoconia matrix. AB - This study was designed to investigate patterns of fibrils organization in histochemically stained otoconia. Transmission electron microscope and video imaging were used. These data indicate that otoconia of the chick (Gallus domesticus) inner ear may have central cores in vivo. The data also show that the ultrastructural organization of fibrils fixed with aldehydes and histochemical stains follows trajectories that conform to the hexagonal shape of otoconia. These changes in direction may contribute to the formation of a central core. The existence of central cores is important for the in vivo buoyancy of otoconia. Packing of fibrils is tighter after phosphotungstic acid (PTA) stained otoconia than with other histochemical stains, which usually produce looser packing of fibrils and seemingly larger central core. TEM of tilted and untilted material showed that turning of fibrils occurs at the points where the face angles of otoconia form and where central cores exist. Video image processing of the images allowed reconstructing a template which, if assumed to repeat and change trajectories, would fit the pattern of fibrils seen in fixed otoconia. Since it is highly unlikely that aldehyde primary fixation or PTA stain caused such drastic change in the direction of fibrils, the template derived from these results may closely approximate patterns of otoconia fibrils packing in vivo. However, if the above is correct, the perfect crystallographic diffraction pattern of unfixed otoconia do not correspond to patterns of fixed fibrils. PMID- 8358081 TI - Software for quantitative immunogold and in situ hybridization. AB - A well-deserved criticism of stereology is that it is often too difficult to understand and use. Nevertheless, it is rapidly becoming one of the most effective ways of collecting and interpreting structural data in experimental biology. Recent breakthroughs in theory have produced a remarkable set of tools that can be used to engineer new methods. The dilemma remains, however, in that some of these new methods continue to be too difficult to understand and use. One solution to this growing problem of technology transfer might be to simplify the methods with computer software. To test this idea, programs were written for quantitative immunogold and in situ hybridization. Simulators were used to develop and test new experimental designs, which, in turn, were translated into step-by-step laboratory tool kits. This paper shows how these tool kits can turn two-dimensional section data into estimates for the number of labeled molecules in three-dimensional organelles, cells, tissues, and organs. The results indicate that software can identify the key data of an experiment and reduce the computational requirements of a new stereological method to entering constants and variables into data entry forms. PMID- 8358083 TI - High-resolution transmission electron microscopy of hexagonal and rhombohedral molybdenum disulfide crystals. AB - Natural (molybdenite) and synthesized molybdenum disulfide crystals have been studied by high-resolution transmission electron microscopy. The image simulation demonstrates that the [0001] and [0110] HRTEM images of hexagonal and rhombohedral MoS2 crystals hardly disclose their stacking sequences, and that the [2110] images can distinguish the Mo and S columns along the incident electron beam and enable one to determine not only the crystal structure but also the fault structure. Observed [0001] images of cleaved molybdenite and synthesized MoS2 crystals, however, reveal the strain field around partial dislocations limiting an extended dislocation. A cross-sectional image of a single molecular (S-Mo-S) layer cleaved from molybdenite has been observed. Synthesized MoS2 flakes which were prepared by grinding have been found to be rhombohedral crystals containing many stacking faults caused by glides between S/S layers. PMID- 8358082 TI - Software for counting cells and estimating structural volumes with the optical disector and fractionator. AB - We describe MS-DOS software for the optical volume fractionator (OVF), a stereological method combining the principles of the optical disector (Gundersen et al.: Acta Pathol. Microbiol. Immunol. Scand., 96:857-881, 1988) and fractionator (Gundersen: J. Microsc., 143:3-45, 1986). The OVF program estimates the volume of a fixed and embedded structure, the numerical density of cells, and the total number of cells in a structure. The hardware requirements include a PC computer (386 or 486 with VGA graphics) and a conventional light microscope fitted with a rotating stage, extension tube, and length gauge. The software includes an introduction, tutorial, simulator, laboratory tool kit, and report generator. The tool kit improves the efficiency of gathering stereological data with light microscopy and offers a convenient link between the data of light and electron microscopy. A novel algorithm, based on fractionator sampling, gives the volume of a fixed and embedded structure from the same set of sections used for cell counting. A laboratory example illustrates the operation of the software. PMID- 8358084 TI - A simplified mode of differential phase contrast Lorentz microscopy. AB - A simplified mode of differential phase contrast Lorentz microscopy for the study of magnetic domain structures in thin films is proposed and demonstrated. This mode employs a single annular detector in a scanning transmission electron microscope rather than the specialized split detectors that have been previously used. The resulting signal is sufficiently linear with magnetic field strength to allow quantitative data to be obtained on the domain configurations and the natures of the domain walls. PMID- 8358085 TI - A novel method for the cross-sectional TEM preparation of thin films deposited onto water-soluble substrates. AB - A preparational method was developed solving the problem of cross-sectional TEM preparation of thin films and layer systems deposited onto water-soluble substrates. The technique is based on the replacement of the sample onto steady substrate, followed by mechanical and ion beam thinning. Cross-sectional TEM micrographs of Ag and Ag/Ag2Se layers are shown presenting the efficiency of this novel technique. PMID- 8358086 TI - Yet another artifact of quantitative immunocytochemistry in electron microscopy: serial sections reveal inconsistent labeling. PMID- 8358087 TI - Medical education: Providence and Bologna. PMID- 8358088 TI - The Brown University School of Medicine class of 1993. PMID- 8358089 TI - The "reading" of patients. PMID- 8358090 TI - The status of women in medicine at the Brown University School of Medicine. AB - Although the number of women medical faculty appointed and promoted at the School of Medicine has increased gradually since 1987, the extent to which women have advanced in academic medicine and the timeliness of their movement forward are of concern. With women constituting nearly 20% of the medical faculty at Brown, and comprising only 5% of professorial appointments, it is easy to see the disparities. While the Brown University School of Medicine stands out as one of less than a dozen medical schools with an Office of Women in Medicine, clearly there is still much to accomplish in this domain. Progress may be accelerated through networking and advocacy promoted by professional development programs sponsored by offices for women in medicine and organizations as RIMWA. Offering women medical faculty a forum to discuss issues as departmental promotion criteria in academic medicine and to link up with other women physicians, ultimately serves not only women faculty but their institution. Providing role models is critical to assist women medical students in looking well ahead to plan for their own career development. In creating opportunities for dialogue among women in medicine at all levels in the medical school environment and among women physicians in the nearby community, institutions take an essential step forward towards supporting women's advancement in medicine. PMID- 8358091 TI - The practicing physicians of Rhode Island: a statistical profile. PMID- 8358092 TI - The unifying principles of family medicine: a historical perspective. PMID- 8358093 TI - Carrot juice xanthoderma: an orange patient with multiple myeloma. PMID- 8358094 TI - Patient education for screening mammography: the unmet need. PMID- 8358095 TI - Chloroquine stimulates the mitogen-driven lymphocyte proliferation in patients with psoriasis. AB - Chloroquine is known to exacerbate psoriasis. Since immunological stimuli are considered to be important for the pathogenesis of psoriasis, we compared the effects of chloroquine on cell-mediated immunity in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin (PHA)-induced uptake of 3H-thymidine to measure lymphocyte proliferation. Chloroquine was added to the cultures at concentrations ranging from 0.022 to 220 microM. We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (p < 0.002). The spontaneous blastogenesis in both controls and patients remained stable under chloroquine. In PHA-driven cultures in controls, 0.022-2.2 microM chloroquine had no effect, higher concentrations of the drug suppressed proliferation. In patients, 22 microM chloroquine surmounted the suppression of the PHA-induced proliferative response found in controls; moreover, 2.2-0.022 microM chloroquine increased lymphocyte proliferation by > 300% (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally stimulated by the addition of pharmacological doses of chloroquine. PMID- 8358096 TI - Pitting scars in progressive systemic sclerosis. AB - The digital pitting scar is a common clinical feature in patients with progressive systemic sclerosis (PSS). Its pathogenesis is unclear, but it may result in small ulcerations. The clinical and histological features of these lesions are poorly understood. Eighty-seven patients with PSS were examined at least once per year. Pitting scars were defined as pinhole-sized digital concave depressions with hyperkeratosis. They were seen in 34 cases (39%) and were located not only on the tips of the fingers, but also on the sides, especially on the radial border of the index and middle finger and the ulnar side of the thumb, where they had a linear arrangement. Additional pitting scars were noticed on the dorsal surface of the proximal interphalangeal and metacarpophalangeal joints. Pitting was closely associated with several signs of PSS, e.g. Raynaud's phenomenon, skin thickening or articular involvement (e.g. stiffness, swelling, pain). There was no relationship between the number of pitting scars and the duration of PSS. Biopsy samples were taken of the lesions on the lateral sides of fingers in 3 patients. Histologically, there was a plug-like hyperkeratosis with parakeratosis, homogenized collagen fibers and slight perivascular mononuclear cell infiltration. Calcification and altered collagen fibers were observed in the deep dermis. Although pitting scars of the fingertips may be different from those of the lateral sides of the fingers, both histologically and pathogenetically, they were similar clinically. The scar locations on the fingertips and finger joints (proximal interphalangeal and metacarpophalangeal) suggest that exogenous trauma, vibration injury and/or cold exposure may play a role in their pathogenesis. PMID- 8358097 TI - Occupational dermatitis from isothiazolinones in the nylon production. AB - Kathon is a biocide consisting of a mixture of two isothiazolinone derivatives (5 chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one) in an approximate ratio of 3:1, respectively, and with MgCl2 and Mg(NO3)2 present as stabilizers. The isothiazolinones are marketed under several brand names, and the concentration of the active ingredient varies according to their intended application. At a concentration of 3-15 ppm it shows activity against a wide spectrum of fungi, gram-positive and gram-negative bacteria. Contact allergy to it has been caused by cosmetics and also by products used in the pottery and various other industries. Recently we had the opportunity to observe 6 cases of occupational allergic contact dermatitis from an isothiazolinone mixture named Grotan TK 2 in a large textile industry producing nylon. An oil emulsion containing isothiazolinones is used in the spinning phase of the work cycle to prevent bacterial contamination that would damage yarn quality; furthermore, it helps to decrease the electrostatic charge that is produced by high speed at which the yarn moves and also to decrease the breakage possibility. PMID- 8358098 TI - Contact immunotherapy with squaric acid dibutylester for warts [corrected]. AB - The efficacy of squaric acid dibutylester (SADBE), a topical allergen, was investigated in the treatment of 20 patients with warts. All patients had multiple or warts recalcitrant to other therapies or hesitated to have the painful cryotherapy. The patients with warts present for a mean of 15.3 months (range 1-36) were successfully sensitized with 2% SADBE in acetone. Then the warts were treated with a 0.1 or 0.01% SADBE application once a week or every other week, so as to maintain a mild contact dermatitis. Twelve of the 20 patients (60%) were completely cured after an average of 6 applications (range 2 12). Five patients (25%) showed either a poor or no response even after 9-18 applications. Three patients (15%) exhibited contact dermatitis either at the sensitization or the treatment site. Our study shows that this therapy, although not always safe, is effective in treating warts in some patients, who either hesitate at conventional cryotherapy or have warts resistant to other therapies. The safety of this method remains to be evaluated. PMID- 8358099 TI - Microcystic adnexal carcinoma. Case report with an immunohistochemical study. AB - We report the case of 71-year-old Japanese woman with microcystic adnexal carcinoma (MAC) of the nose. Our histological and immunohistochemical observations suggest that MAC has both pilar and eccrine sweat gland differentiation. PMID- 8358100 TI - Subcorneal pustular dermatosis and IgA myeloma. AB - A case of subcorneal pustular dermatosis (SCPD), as a presenting feature in a patient with multiple myeloma, is described. This is the seventh case report of this association and the first from the Middle East. Five of these cases, including the present report, have been of the IgA paraprotein type, IgA intraepidermal deposits have been described in a few patients with SCPD associated with IgA paraproteinaemias but have not been detected in our patient. PMID- 8358101 TI - Diffuse erythrodermic cutaneous mastocytosis with bone marrow infiltration. AB - We report a case of diffuse erythrodermic cutaneous mastocytosis with bone marrow infiltration. An 11-month-old female patient was referred to our hospital for intermittent flushing, fever, intense itching, erythematous rash and bullous lesions. Cutaneous biopsy demonstrated diffuse cutaneous mastocytosis. The bone marrow aspirate revealed mast cell infiltration. Ketotifen treatment was very effective. PMID- 8358102 TI - Aquagenic pruritus as a presenting symptom of polycythemia vera. AB - A female patient was presented because of a prickling sensation that appeared shortly after warm water contact. Examination revealed no abnormality, but water exposure was followed by pruritus without any visible skin changes. Blood and bone marrow examinations revealed abnormalities typical of polycythemia vera. Skin biopsy before and after warm water challenge showed increased numbers of mononuclear cells in the papillary dermis and epidermis particularly after water exposure. Phlebotomy was associated with prompt cessation of pruritus. PMID- 8358103 TI - Pigmentary demarcation lines of pregnancy with erythema. AB - We describe two patients with pregnancy-associated pigmentary demarcation lines overlapped by erythematous changes. In both cases, there was a symmetrical well defined erythematous pigmentation involving the buttocks and flexor aspects of the legs. After normal delivery the erythema disappeared within 7-10 days, followed by slow resolution of the pigmentation. Compression by the enlarged uterus of peripheral nerves issuing at S1-S2 is proposed as a mechanism of these changes. PMID- 8358104 TI - Psoriasis and birdshot chorioretinopathy: response to aromatic retinoids. AB - Birdshot chorioretinopathy, also known as vitiliginous chorioretinitis, is a rare and serious retinochoroidopathy. We describe a case in a patient with long standing typical psoriasis. To our knowledge this association has not been previously reported in the dermatologic literature. Both psoriasis and chorioretinitis appeared to respond to aromatic retinoids. The incidence of birdshot chorioretinopathy in patients with psoriasis should be assessed. PMID- 8358105 TI - Fingertip tophi without gouty arthritis. AB - We report 2 patients without a history of acute gouty arthritis showing tophi located only on the fingertips, an unusual location. A review of the literature found a few similar reports; these patients might represent a subgroup of gout characterized by: (1) elderly patients, from the 7th to 9th decades; (2) hyperuricemia; (3) absence of a history of acute gouty arthritis; (4) tophi in the fingertips or fingerpads; (5) chronic renal failure, and (6) all taking drugs or suffering from a disease that affects urate renal excretion. PMID- 8358106 TI - Juvenile hyaline fibromatosis with skull-encephalic anomalies: a case report and review of the literature. AB - We report a case of juvenile hyaline fibromatosis. Besides the typical features of this syndrome, skull and encephalic abnormalities, not previously mentioned, are described. Clinical and microscopic characteristics, therapeutic possibilities and different theories concerning histopathogenesis are discussed. PMID- 8358108 TI - Odor in pemphigus. PMID- 8358107 TI - Use of topical lithium succinate in the treatment of seborrhoeic dermatitis. PMID- 8358109 TI - Is sustained production of tumor necrosis factor-alpha relevant to the development of pustular psoriasis? AB - Tumor necrosis factor-alpha (TNF-alpha) has been implicated as one of the critical mediators of psoriasis. Evidence for an important role on the progression of the disease is increasing, while recent clinical studies have suggested its beneficial role in the disease. Based on the results of our sequential analysis of the serum cytokine levels in a patient with pustular psoriasis, we speculate that immunologic effects of constitutive local release of TNF-alpha may be quite different from those of its systemic injection. PMID- 8358110 TI - Drug hypersensitivity syndrome. AB - Some types of hypersensitivity to drugs are defined either by the generic name of the drug or descriptive terms. They are sometimes assimilated to pseudolymphoma because the causative drugs are often the same, although the eruption lacks clinical and histopathological criteria of pseudolymphoma. It is then suggested to use 'idiosyncratic drug hypersensitivity syndrome' to define this type of drug reaction. As the skin and other organs may be involved, a generic name would help to determine a better definition and a surveillance program. PMID- 8358111 TI - Melanocytic nevi and tumor progression: perspectives concerning histomorphology, melanoma risk and molecular genetics. AB - Atypical variants of melanocytic nevi such as congenital nevi, acral nevi and Spitz nevi may share many architectural and cytologic abnormalities in common with conventional dysplastic nevi. Although largely undetermined, the degree of melanoma risk (if any) associated with the atypical nevus in question may correlate with the grade of atypia in the particular nevus and a variety of other factors such as the number of nevi and skin phototype. PMID- 8358113 TI - 'Anti-metastatic' nm23 gene product expression in keratoacanthoma and squamous cell carcinoma. AB - An inverse correlation has been demonstrated between nm23 gene expression and metastasis. The gene is located on chromosome 17q (q1.1-q2.1), a region distinct from tumour suppressor gene p53. We have previously reported expression of mutant products of p53 gene to be significantly associated with worsening degrees of differentiation in squamous cell carcinoma. nm23 gene product, which shows complete identity to human erythrocyte nucleoside diphosphate kinase, was used to raise an affinity-purified polyclonal antibody Ab-11 which is applicable to formalin-fixed and paraffin-embedded tissues. Keratoacanthomas and squamous cell carcinomas of the epidermis form a fascinating human tumour model in which to test the hypothesis that the nm23 gene confers 'anti-metastatic' properties, since the former never metastasise while the latter have this potential. Two observers rated immunohistochemistry for the nm23 gene product as the proportion of tumour positive from grades 1-4 (corresponding to 25, 50, 75 and 100% of tumour cells stained). Nineteen typical keratoacanthomas, 20 well, 21 moderately and 8 poorly differentiated epidermal squamous cell carcinomas were studied. The Jonckheere-Terpstra test statistic of association between staining grade and lesion type was 762.5, p = 0.189 (2 tails), p = 0.0945 (1 tail). There was no statistically significant trend in tumour staining from keratoacanthoma through decreasing grades of differentiation of squamous cell carcinoma. nm23 product expression does not appear to correlate with differentiation, itself an indicator of metastatic potential, in this system of human squamous cell neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358114 TI - Gene therapy. PMID- 8358112 TI - Plastic occlusion stress test as a model to investigate the effects of skin delipidization on the stratum corneum water holding capacity in vivo. AB - The purpose of the study was to develop an in vivo model to study the effects of lipid removal on skin barrier. 16 subjects (age 41 +/- 8) were delipidized in vivo on the volar forearm using respectively ether/acetone (EA; 1:1) and chloroform/methanol (CM; 2:1). A third site served as control. Water holding capacity (WHC) was measured according to the plastic occlusion stress test (POST) procedure: the water desorption curve after removal of the occlusion was recorded in terms of skin surface water loss (SSWL) using an evaporimeter for 30 min. In the central part of the evaporation curve (bound water) the CM-treated site is significantly different from control and EA-treated sites (p < 0.01). The SSWL decay constants reflecting the desorption rate of water from SC are higher in the CM-treated site (p < 0.01). The data are consistent with the effect of CM delipidization (polar lipids) on bound water. No differences are recorded in the evaporation of free water. We conclude that polar lipids have a key role in modulating barrier function and WHC of the stratum corneum. The POST can represent a useful in vivo model to study the effects of lipid extraction on skin function. PMID- 8358115 TI - Postoperative pneumonia in elderly patients: incidence and mortality in comparison with younger patients. AB - To determine whether elderly patients have an increased incidence of postoperative pneumonia and/or an increased mortality, we conducted a retrospective study of 4,380 patients who underwent thoracic, abdominal or neurosurgery under general anesthesia. Thirty of these patients developed postoperative pneumonia (incidence, 0.68%). The elderly patients aged 65 years or older who underwent thoracic surgery had the highest incidence of pneumonia. Nine of the 30 patients with pneumonia died (mortality, 30%). Elderly patients did not show a higher mortality than the younger patients. The extent of pulmonary infiltrates on chest roentgenogram and the serum bilirubin level, both of which were determined at the onset of pneumonia, independently had a significant association with mortality. Our study suggests that advanced age is a risk factor for postoperative pneumonia in patients who undergo thoracic surgery. PMID- 8358116 TI - Lung abscess: analysis of 66 cases from 1979 to 1991. AB - Sixty-six patients with bacterial lung abscess were treated between 1979 and 1991 in our hospital. Among these patients, death occurred in one of the 42 cases of community-acquired infection (mortality rate: 2.4%) and in 16 of the 24 cases of nosocomial infection (mortality rate: 66.7%). Of all 66 cases, 55 were culture positive, and the etiologic agents isolated from 24 of the culture-positive cases were found to be anaerobic bacteria. The most common aerobes isolated from the foci were identified as Staphylococcus aureus, Klebsiella spp. and Pseudomonas aeruginosa, while the most common anaerobes were Bacteroides spp., Peptostreptococcus, Fusobacterium spp., microaerophilic Streptococcus and Veillonella. The mortality was higher in the cases with P. aeruginosa, Klebsiella spp. and Candida spp. than in those with other bacteria. The prognosis of lung abscess patients proved to depend on the presence of underlying diseases and on superinfection with aerobes. PMID- 8358117 TI - Percutaneous transluminal coronary angioplasty for acute myocardial infarction. AB - Between 1986 and 1991, direct coronary angioplasty was attempted in 79 patients. The procedure was successful in 76 patients (96%), unsuccessful without complications in 2 patients, and major complications occurred in 1 patient (ventricular fibrillation and cardiogenic shock). Reperfusion was obtained from 1 to 7.5 hours (mean: 3.3 +/- 1.3 hours) after the onset of chest pain. Among the 76 successfully dilated patients, there was one cardiac death and 68 had predischarge angiography (64 patent, 2 stenosed, and 2 occluded). Although only 33 of the 58 patients (57%) angiographically followed after discharge showed persistence of primary patency, 52 of the 57 (91%) followed further obtained final patency when angioplasty was repeated up to 4 times. These results indicate that direct angioplasty in the community hospital setting can achieve a high primary success rate and a low reocclusion rate. PMID- 8358118 TI - Shunt nephritis: efficacy of an antibiotic trial for clinical diagnosis. AB - Coagulase negative staphylococcus, a normal skin flora, is especially nosopoietic under shunt management, because coagulase negative staphylococcus sometimes forms a biofilm around itself at catheter tips in vivo, which shields the organism from the effects of antibiotics. But it is difficult to distinguish this pathogen from a possible confounding contamination of a blood culture. In this article, we report a case, and discuss how a patient with suspected shunt nephritis should be examined and treated. In addition, to further histological and prognostic interpretation, we review the previously reported cases of shunt nephritis in Japanese adults. PMID- 8358119 TI - Ulcerative colitis in female siblings with an identical human leukocyte antigen haplotype (A24, Bw52, DR52 and DQw1). AB - Two female siblings with ulcerative colitis are reported. Both the 30-year-old elder sister and the 28-year-old younger sister developed bloody stools and diarrhea; ulcerative colitis was diagnosed by endoscopic and histologic examination of the colon. Their maternal aunt also suffered from the disease. Human leukocyte antigen analysis revealed an identical haplotype for the sisters (A24, Bw52, DR2 and DQw1), while the aunt had A24, Bw52 and DR2. The haplotypes of Japanese patients with familial ulcerative colitis are reviewed, and the role of human leukocyte antigens in this disease is discussed. PMID- 8358120 TI - Selective IgM deficiency in a patient with Hashimoto's disease. AB - A 70-year-old man with Hashimoto's disease had selective IgM deficiency, while other immunoglobulin levels were normal. In vitro mixing experiments were carried out in which B cells and T cells from the patient and from a healthy control donor were co-cultured in the presence of pokeweed mitogen, in order to investigate the etiology of IgM hypoproduction. The results indicated that the patient had B-cell dysfunction, involving the impairment of B-cell differentiation. In addition, both IgG of the healthy control donor and thyroid hormone may play important roles in the pathogenesis of this case. PMID- 8358121 TI - Fatal angioedema associated with enalapril. AB - A 37-year-old female with a history of hypertension for 5 years was brought to the emergency room with swelling of the tongue and neck after the second dose of enalapril. After administration of hydrocortisone by her physician, she went to the emergency room. Her dyspnea and dysarthria were relieved. However, she experienced recurrence of the symptoms followed by respiratory arrest. She suffered severe anoxic brain damage and died three days later. Although angioedema is a rare occurrence with the use of enalapril, it is potentially life threatening. PMID- 8358122 TI - Sclerosing peritonitis associated with keratoconjunctivitis sicca, pleurisy, and secretory otitis media. AB - A male case of sclerosing peritonitis of unknown cause, associated with keratoconjunctivitis sicca, pleurisy, and secretory otitis media, is presented. These unusual complications are very similar to the adverse reactions to the beta adrenergic blocking agent, practolol, which is known to cause sclerosing peritonitis. This similarity suggests an etiological association between the sclerosing peritonitis of this case and that caused by practolol. The sclerosing peritonitis of this case may be considered to occur as part of some systemic disorder, and thus casts doubt on the hitherto accepted hypothesis that sclerosing peritonitis results from infectious peritonitis. PMID- 8358123 TI - Lactic dehydrogenase anomaly in a patient with chronic renal failure. AB - A 67-year-old man with chronic renal failure (CRF) was defined to have lactic dehydrogenase (LDH)-immunoglobulin A (IgA) complex, the so-called "LDH anomaly", in his serum and pleural effusion. He was found to have a pleural effusion on the right side during maintenance dialysis at a satellite hospital. A LDH-IgA complex was detected in the serum and pleural effusion by the method of current electrophoresis. The immunoglobulin class was found to be IgA (K) by counter immunoelectrophoresis. LDH anomaly is extremely rare in patients with CRF; the clinical significance of this substance in serum and pleural effusion remains unclarified. PMID- 8358124 TI - Progressive external ophthalmoplegia and myositis. AB - We reported a senile male patient with progressive external ophthalmoplegia (PEO) and myositis. The ophthalmoplegia was severe, but other neuromuscular features were nearly normal. Muscle enzymes in serum were moderately elevated. Autoimmune, endocrinological or malignant diseases were not observed during the previous 4 years. Pathology of non-weak limb muscles biopsied twice was consistent with active inflammatory myopathy. The ragged-red or cytochrome c oxidase-negative fibers, which are a hallmark of mitochondrial myopathy with PEO, were not increased in comparison with age-matched control muscles. Analysis of mitochondrial DNA in muscle by the Southern blot method did not reveal any deletions. It was concluded that the inflammatory myopathy, myositis clinically localized at the ocular muscles, is an important and distinct disorder in PEO. PMID- 8358125 TI - Silent lupus nephritis with fingerprint deposits. AB - A 26-year old woman with diffuse active lupus nephritis showed no proteinuria. Electron microscopy revealed a typical fingerprint pattern in glomerular subendothelial electron dense deposits. Out of 21 renal biopsy cases of lupus nephritis, we found fingerprint deposits in 4 cases (19%) including the present case. All of the cases showed diffuse proliferative glomerulonephritis with overt proteinuria, except the present case. To our knowledge, the present case is the first reported case of active lupus nephritis, where fingerprint deposits were found, with normal urinalysis. PMID- 8358126 TI - A patient with congenital plasminogen deficiency manifesting primary pulmonary hypertension. AB - A 25-year-old Japanese man was diagnosed as having primary pulmonary hypertension, on the basis of the findings of cardiac catheterization and ventilation-perfusion scintiscans. The plasma level of plasminogen in this patient was found to be reduced to 43% by a functional assay and 61 mg/l by an antigenic assay. Based on the family study, the patient was considered to have a heterozygous congenital plasminogen deficiency. Accordingly, it is suggested that the defective fibrinolysis in this patient may have played an important role in the development of primary pulmonary hypertension through microthrombosis. PMID- 8358127 TI - Sleep apnea and palatal myoclonus in a patient with neuro-Behcet syndrome. AB - A 50-year-old man with neuro-Behcet syndrome showed truncal imbalance, dementia, palatal myoclonus, snoring and rhythmic inspiration synchronized with palatal myoclonus. Magnetic resonance imaging showed hypertrophy of the bilateral inferior olivary nuclei with slight pontine atrophy. A polysomnographic recording disclosed sleep apnea during non-REM sleep: 6% central type, 46% mixed type, and 48% obstructive type. We speculate that lesions of the respiratory center or related structures in the brainstem resulted in sleep apnea and that laryngeal myoclonus also affected the apnea. PMID- 8358128 TI - Aseptic localized peritonitis in a patient with chemical meningitis associated with craniopharyngioma cysts. AB - We report a rare case of a young woman with cystic craniopharyngioma who developed not only aseptic chemical meningitis as an initial sign but also aseptic localized peritonitis which was confirmed by the presence of ascites. PMID- 8358129 TI - Increased serum level of interleukin-5 in a patient with episodic angioedema and eosinophilia syndrome. AB - A case of episodic angioedema and eosinophilia syndrome is reported. An 18-year old male suffered from monthly episodes of angioedema, pruritic papules, weight gain, and fever for twelve years. During the episodes, peripheral eosinophils and serum levels of interleukin (IL)-5, an eosinophil proliferating cytokine were elevated. Extensive evaluations disclosed neither visceral involvement nor evidence of parasitic infections, collagen diseases, or neoplastic disorders. Corticosteroid treatment brought about a dramatic clinical improvement concomitant with decrement of eosinophils and serum IL-5 was observed. These observations suggest that IL-5 may be a causative factor for this pathological state. PMID- 8358130 TI - Right ventricular inflow obstruction due to giant hematoma formed by chronic constrictive pericarditis. AB - A 26-year-old man having chronic constrictive pericarditis with rare complications is described. Right ventricular inflow obstruction was caused by an intracavity giant mass which was surrounded by thick calcified pericardium. The mass consisted of old bloody fluid with some calcified tissue. The findings of auscultation closely mimicked those of tricuspid valvular stenosis. PMID- 8358131 TI - Treatment of ulcerative colitis with camostat mesilate, a serine protease inhibitor. AB - We were able to induce and maintain remission with camostat mesilate, a serine protease inhibitor, in two patients with ulcerative colitis, to whom salicylazosulfapyridine could not be administered due to previous side effects. The enzymatic activity of proteases from granulocyte, pancreatic juice and bacteria is possibly harmful to the inflamed colonic mucosa. Camostat mesilate can be expected to have an anti-inflammatory effect on the damaged mucosa of inflammatory bowel disease. PMID- 8358132 TI - Imported Plasmodium malariae malaria. PMID- 8358133 TI - Depression and the experience of chronic back pain: a study of related variables and age differences. AB - OBJECTIVE: To document the prevalence of depression and examine the relationship between depression and selected pain-related variables associated with chronic back pain among elderly and nonelderly samples. DESIGN: Survey with mailed questionnaire. SETTING: Patients seeking treatment at a spine diagnostic and treatment center. PATIENTS: Consecutive sample of elderly subjects (n = 69). Nonelderly subjects (n = 59) were randomly selected to achieve a sample size comparable to the elderly. Evaluation of depressed mood was determined by Beck Depression Inventory. MAIN OUTCOME MEASURES: Multidimensional Pain Inventory, Pain Disability Index, Pain Duration, Work-Related Disability, Medication Use, and Pain Severity. RESULTS: A high prevalence of dysphoria was found in both age groups. No significant differences were found between age and depressed mood. The only significant association between depressed mood and age occurred with pain duration, with the elderly experiencing fewer total hours per day in pain. Combining age groups, multivariate analysis of variance revealed that dysphoric chronic pain patients reported more antidepressant use, greater pain intensity, greater interference due to pain, and less life control than the nondepressed patients. Interference in activities demonstrated the strongest relationship with depressed mood in both age groups. CONCLUSIONS: There is a high prevalence of dysphoria in both the elderly and nonelderly with chronic back pain. The relationships between pain-related constructs and depressed mood in chronic back pain patients are similar in the elderly and nonelderly. The impact of the pain experience on the individual's activities, functioning, and feelings of life control should be considered in theoretical and clinical explanations of the association between pain and depression. PMID- 8358134 TI - Predictors of response to pain management treatment. The role of family environment and changes in cognitive processes. AB - OBJECTIVE: The purpose of the present study was to examine factors that influence individual differences in treatment response after multidisciplinary pain management. DESIGN: Pre-post assessment design. PATIENTS: 119 chronic pain inpatients. MAIN MEASURES: Outcome measures included pain report from the McGill Pain Questionnaire, emotional distress from the Symptom Checklist-90 Revised, and activity discomfort from the Activity Discomfort Scale. Process measures included the Family Environment Scale, the Coping Strategies Questionnaire, and the Inventory of Negative Thoughts in Response to Pain. RESULTS: Results indicated that pretreatment family environment, cognitive coping strategies, and negative thinking accounted for small yet significant proportions of the variance in outcome. The proportion of variance accounted for by the changes in cognitive coping and negative thinking was somewhat higher. An increase in pain control and rational thinking was related to decreases in depression and anxiety, pain report, and activity discomfort. Decreases in negative social cognitions were related to decreased depression at posttreatment. CONCLUSIONS: Changes in coping strategies and negative thinking may be important mechanisms related to improvement, or lack of improvement, in a range of outcome measures. Patients from families who are controlling and disorganized, and patients high on negative thinking at pretreatment may represent high-risk groups in need of further individually tailored interventions. PMID- 8358135 TI - False-positive rates of cervical zygapophysial joint blocks. AB - OBJECTIVE: To determine the false-positive rate of anesthetic blocks of the medial branches of the cervical dorsal rami in the diagnosis of cervical zygapophysial joint pain. DESIGN: Comparison between single diagnostic blocks, and a criterion standard of double-blind, controlled, differential anesthetic blocks. SETTING: Tertiary referral center. PATIENTS: The first 55 consecutive patients with neck pain for > 3 months after and attributable to a motor vehicle accident, and who had completed a second diagnostic block after an initial positive response. A total of 60 joints was studied, with five patients providing two joints each. The mean age was 41 years; 61% were female. METHODS: Each patient had been investigated with radiologically controlled blocks of the medial branches of the cervical dorsal rami to anesthetize the target cervical zygapophysial joint. The initial block was performed using either 0.5% bupivacaine or 2% lignocaine, randomly selected. The duration of pain relief was assessed in a double-blind fashion. The procedure was repeated with the complementary anesthetic. Only patients experiencing a longer period of pain relief from bupivacaine were considered to have true-positive responses. RESULTS: The second block failed to relieve pain in two of the tested joints. In a further 14 joints, the control blocks relieved pain, but the patient failed to correctly discriminate the longer acting anesthetic. The remaining 44 joints met the criteria for true-positive responses. The false-positive rate of single blocks was 16 of 60 or 27% (95% confidence interval 15%, 38%). CONCLUSIONS: Uncontrolled diagnostic blocks are compromised by a significant false-positive rate that seriously detracts from the specificity of the test. PMID- 8358136 TI - Pain clinic records: a comprehensive form and computerized database. PMID- 8358137 TI - Combined stellate ganglion and sphenopalatine ganglion block in acute herpes infection. PMID- 8358138 TI - Head banger's whiplash. AB - OBJECTIVE: The current trend in dancing includes "head banging" with extreme flexion, extension, and rotation of the head and cervical spine. We suggest that dance-related severe pain in the cervical area may result from head banging. DESIGN: A cohort of 37 eighth graders ages 13 or 14 participated in a dance marathon for charity lasting 7 h. There were 26 girls and 11 boys. SETTING: During the dance marathon, three "heavy metal" songs were played during which head banging could be done. PATIENTS: The painful syndromes that relate to head banging were evaluated by a convenience sample of the 37 marathon dancers in the eighth grade. INTERVENTIONS: None. MAIN OUTCOME MEASURES: A self-selected age matched control group is included since 17 adolescents participated in head banging and 20 did not. RESULTS: Of the head bangers, 81.82% of the girls and 16.6% of the boys had resultant cervical spine pain that lasted 1-3 days. Only 26.2% of non-head-banging girls and 0% of non-head-banging boys had cervical spine pain lasting 1-3 days. Of all the 8th-grade participants, 62.16% had pain somewhere. Other types of pain included leg pain, back pain, and headache. Only three adolescents took any medication for their pain. CONCLUSIONS: The head banger's whiplash is a self-limiting painful disorder. The easy resolution of the pain problem in adolescents is a tribute to the resilience of youth. PMID- 8358139 TI - In response to letter by Drs. Clarke, Hill, and Barnes. PMID- 8358140 TI - In response to RSD article by Dr. Ochoa. PMID- 8358141 TI - In response to RSD editorial by Dr. Wilson. PMID- 8358142 TI - Errors and artifacts. PMID- 8358143 TI - McGill Pain Questionnaire translated into Danish: experimental and clinical findings. AB - OBJECTIVE: To develop a methodology for translating the McGill Pain Questionnaire (MPQ) into a Danish version, and to make comparisons to studies of patients speaking other languages. DESIGN: Finding suitable Danish adjectives using the same methodology as that in the original MPQ. Comparison of Danish descriptors to the words in the English version of MPQ. Survey in healthy subjects and patients with rheumatoid arthritis (RA) and fibromyalgia (F). SETTING: The general public and hospital outpatients. PATIENTS: A random sample of 186 healthy volunteers, 20 patients with rheumatoid arthritis and 41 patients with fibromyalgia. MAIN OUTCOME MEASURES: Danish words translated as closely as possible to the descriptors in the original McGill Pain Questionnaire. A pain-assessment instrument making international pain description possible. RESULTS: A Danish version of the McGill Pain Questionnaire was developed with scale values of Danish descriptors not differing more than 5 x SEM from the 'patient' words in the English version. The subdivision into classes and subclasses was respected. In the reliability experiment, the same rank values were found in 85% of subclasses. In a study using two experimental pain stimulus intensities, seven of 10 subjects obtained higher MPQ scores following the high-intensity stimulus. In the clinical study, the pain profiles of patients with RA and F in English, Italian, and Danish patients were almost the same. CONCLUSION: The present methodology of translating the McGill Pain Questionnaire permits comparison of studies from English-speaking and non-English-speaking populations, thus facilitating international research exchange. PMID- 8358144 TI - Physiological correlates of painful stimulation in preterm infants. AB - OBJECTIVE: The study investigates the physiological responses of preterm infants to procedures that are routinely performed in intensive care nurseries. Changes in heart rate, respiration rate, and oxygen saturation were examined as indicators of the level of discomfort experienced by the infant during the procedures. DESIGN: Clinical descriptive. Systematic observations of the infants were conducted during periods of rest as well as during routine interventions. SETTING: All observations were recorded from monitored preterm infants in the intensive care units of two urban hospitals. PATIENTS: Thirty-five preterm infants 24-30 weeks gestational age and weighing < 2,000 g at birth. Data were collected from all infants in the units who met the weight criterion. INTERVENTIONS: The researchers observed the infants while the intensive care nursery staff were performing routine care procedures. Observations were made during procedures that adults would consider to be painful, such as injection, heel stick, tape removal, and squeezing of the heel to induce blood flow after heel stick, as well as nonpainful procedures, such as handling, temperature taking, alcohol swabbing, patting, taping a tube, feeding, and placing a pacifier. MAIN OUTCOME MEASURES: Heart rate, respiration rate, and oxygen saturation were recorded from infant monitors. Mean values of the three measures during procedures were compared with mean values before and after procedures. RESULTS: Significant differences (p < 0.001) were found among pre-, peri-, and post-procedures for all three outcome measures. Heart rate and respiration rate means were significantly (p < 0.001) higher during procedures that adults consider to be painful than in those regarded as nonpainful. Oxygen saturation was lower (p < 0.001) for painful procedures than for nonpainful procedures. Gender and infant size comparisons yielded inconclusive results. CONCLUSION: The outcome measures appear to be reliable indices of preterm infant responses to painful stimulation. PMID- 8358145 TI - Strategies for coping with pain and psychological distress associated with temporomandibular joint osteoarthrosis and internal derangement. AB - OBJECTIVE: To analyse the relationship among a variety of emotional, cognitive, and behavioral coping strategies and pain/suffering and psychological distress in patients with temporomandibular joint (TMJ) pain. DESIGN: Cross-sectional, correlational study. SETTING: Department of Oral and Maxillofacial Surgery, University Hospital Groningen. SUBJECTS: A consecutive sample of 53 patients with a mean age of 25 with TMJ osteoarthrosis and internal derangement or synovitis without internal derangement. There were seven men and 46 women. No patient was excluded. MAIN OUTCOME MEASURES: Pain/suffering was assessed using the West Haven Yale Multidimensional Pain Inventory and visual analogue scales. Psychological distress was assessed by the General Health Questionnaire and the Symptom Checklist. Coping with pain was assessed by the Coping with Specific Symptoms Questionnaire. RESULTS: Psychological distress and pain severity were low, and there was little interference by pain with daily life. While none of the coping strategies were frequently used, these strategies did explain a significant proportion of the variance in pain and psychological distress measures (27-58% of the variance). Stepwise regression analysis showed that patients scoring high on expression of emotions and wishful thinking had significantly higher levels of pain/suffering and psychological distress. CONCLUSIONS: Previous studies of other subgroups of patients with temporomandibular disorders (TMDs) report higher degrees of psychological distress. The need to distinguish between specific subgroups of patients with TMD is emphasized by the results of this study. Cognitive-behaviorial interventions to improve ways of coping is not very useful for the subgroup in this study. PMID- 8358146 TI - N-glycosylation in trypanosomatid protozoa. AB - Trypanosomatid protozoa are parasites of considerable medical and economic importance in developing countries. The pathway leading to N-glycosylation in these microorganisms is characterized by the following features: (i) dolichols are composed of only 10-13 isoprene units; (ii) oligosaccharides transferred in N glycosylation have the compositions Man(6,7,9)GlcNAc2, depending on the species; (iii) trypanosomatids are unable to synthesize dolichol-P-Glc and, in addition, some species lack certain dolichol-P-Man-dependent mannosyltransferases; (iv) the oligosaccharyltransferase does not require the presence of glucose units in the oligosaccharide in order to catalyse an efficient transfer reaction; (v) trypanosomatids have a glucosidase II-like enzyme, but lack glucosidase I; (vi) glucosidase II is required for deglucosylation of oligosaccharides glucosylated by the UDP-Glc:glycoprotein glucosyltransferase, an activity first detected in those parasites; (vii) the structures of polymannose-type compounds in these protozoa have no significant differences with those of their mammalian counterparts except for the presence, in certain species, of oligosaccharides having galactofuranose units linked to external mannose residues; (viii) biantennary complex-type oligosaccharides having in some cases terminal alpha linked galactose units or poly-N-acetylactosamine extensions, but lacking sialic acid units, have been described in Trypanosoma brucei; (ix) complex-type oligosaccharides having alpha-linked galactose, fucose and sialic acid residues have been described in Trypanosoma cruzi. In this parasite, addition of sialic acid units to glycoproteins and glycolipids is mediated by a trans-sialidase located on the external surface of the parasite and not by an intracellular CMP sialic acid-dependent sialyltransferase. PMID- 8358147 TI - Sialic acids as important molecules in the regulation of the immune system: pathophysiological implications of sialidases in immunity. PMID- 8358148 TI - O-linked fucose and other post-translational modifications unique to EGF modules. AB - Three types of unusual post-translational modification have been found within conserved amino acid sequences in epidermal growth factor homology regions (EGF modules) of some multidomain proteins. beta-Hydroxyaspartate and beta hydroxyasparagine are found within -Cys-Xxx-Asp/Asn-Xxx-Xxx-Xxx-Xxx-Tyr/Phe-Xxx Cys-Xxx-Cys- sequences. (Xyl alpha 1-->3)Xyl alpha 1-->3Glc beta 1-->O-Ser glycans at conserved sites within -Cys-Xxx-Ser-Xxx-Pro-Cys- sequences have been reported in several proteins. Fuc alpha 1-->O-Thr/Ser modifications have been found at conserved sites within -Cys-Xxx-Xxx-Gly-Gly-Thr/Ser-Cys- sequences. More recently, it has been discovered that the Ser residue corresponding to the potential O-fucosylation site in human factor IX carries the novel tetrasaccharide NeuAc alpha 2-->6Gal beta 1-->4GlcNAc beta 1-->3Fuc alpha 1-->O Ser; this tetrasaccharide can be considered to be an extension of the Fuc alpha 1 ->O moiety. The consensus sequences for these post-translational modifications are in close proximity to each other; e.g. human factor IX has all three unusual modifications within a 12 amino acid linear sequence. In proteins with multiple EGF modules, the O-glycosidic modifications have been found only within the N terminal EGF module; beta-hydroxyaspartate/asparagine residues are not restricted in the same fashion. Little is known yet about the functions of, or possible relationships between, any of these modifications. PMID- 8358149 TI - Human non-secretory ribonucleases. I. Purification, peptide mapping and lectin blotting analysis of the kidney, liver and spleen enzymes. AB - Human non-secretory neutral ribonucleases (RNases) from kidney, liver and spleen have been purified and characterized. SDS-PAGE indicates that all three RNases are highly purified and have apparent mol. wts of 17-18 kDa. Kinetic analysis indicates that all three RNases have a broad pH optimum centred around 6.5, and all three have similar substrate specificities with significant preference for RNA and poly(U) when compared to poly(C), poly(A) and poly(G). All of the above data, as well as immunoblotting data using three polyclonal antibodies (anti human liver RNase, anti-human pancreatic RNase, anti-human eosinophil-derived neurotoxin), indicate that the three proteins are highly purified and are non secretory RNases (IIN). Further characterization by cyanogen bromide peptide mapping and extensive lectin blotting indicated no significant differences between the three human RNases. All three RNases appear to have very similar, if not identical, protein backbones and all three are glycoproteins which are recognized by lectins with specificity for GlcNAc, Fuc and, to a lesser extent, with specificity for Gal beta(1-4)GlcNAc. No significant tissue-specific differences were found among the three human non-secretory RNases. PMID- 8358150 TI - Human non-secretory ribonucleases. II. Structural characterization of the N glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry. AB - The N-glycans have been removed by peptide-N-glycosidase F (PNGase F) from purified human non-secretory RNases derived from kidney, liver and spleen. The spleen RNase was purified by two procedures, one of which did not include the usual acid treatment step (0.25 M H2SO4, 45 min, 4 degrees C), to determine if acid treatment alters the carbohydrate moieties. The N-glycans of the RNases were fractionated by Bio-Gel P-4 chromatography and analysed by 600 MHz 1H-NMR spectroscopy and electrospray mass spectrometry. All four non-secretory RNase preparations contained the following structures: [formula: see text] The relative amounts of the trisaccharide, pentasaccharide and hexasaccharide appeared to vary slightly in the different tissue RNases. The overall results indicate: (i) that acid treatment during purification does not alter the N-glycans of non-secretory RNases; (ii) that the N-glycans from kidney, liver and spleen non-secretory RNases are very similar, if not identical, to one another, but different from the N-glycan structures reported for secretory RNase. PMID- 8358151 TI - Structural characterization of novel inositol phosphosphingolipids of Tritrichomonas foetus and Trichomonas vaginalis. AB - Two major ethanolamine phosphate-substituted inositol phosphosphingolipids have been identified in the unsaponifiable acidic lipid fractions of Tritrichomonas foetus and Trichomonas vaginalis. The compounds were radiolabelled and purified by high-performance thin-layer chromatography followed by high-performance liquid chromatography. The structures were determined by a combination of tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR) experiments, and gas liquid chromatography of components obtained by degradation and derivatization. Inositol in the T. foetus component was 1-linked to the phosphosphingolipid, had the phosphoethanolamine group at the 3-position and a fucosyl residue at the 4 position. The T. vaginalis component lacked the fucosyl moiety. Both organisms also produced inositol phosphosphingolipids having the same long-chain base (sphingosine or dihydrosphingosine) and the same fatty acyl distribution as the inositol diphosphate compounds. These glycosphingolipids may represent metabolic intermediates for new types of membrane anchors for surface glycopeptides or glycolipids that mediate the host-parasite relationship of these trichomonads. The MS/MS and NMR spectroscopic data should provide reference information for structural determinations of other phosphorylated inositol derivatives. PMID- 8358152 TI - Mode of interaction between platelet factor 4 and heparin. AB - Platelet factor 4 (PF4) is a platelet-derived protein capable of binding to, and thus neutralizing, the biological activities of heparin and heparan sulphate. The mode of binding of PF4 to heparin was investigated in a comparative study also involving antithrombin (AT; previously shown to selectively bind a specific oligosaccharide sequence) and fibronectin (FN; non-specific electrostatic interaction). Heparin-derived saccharides were incubated with each of the three proteins, followed by separation of free and protein-bound carbohydrate on a nitrocellulose filter. The interaction systems involved either (i) competition for the protein ligand between 3H-labelled heparin and unlabelled, size fractionated heparin oligosaccharides (isolated after deaminative cleavage with HNO2) or (ii) direct binding of 3H-labelled oligosaccharides. Species smaller than octasaccharides were unable to bind AT, whereas binding to FN and PF4 increased continuously throughout the series, with increasing size of the oligosaccharides. Further separation by anion-exchange chromatography showed that the PF4-binding and FN-binding octasaccharides represented essentially all components present in the initial octasaccharide fraction, the proportion of binding species increasing with charge (hence with the degree of sulphation). The AT-binding octasaccharides, on the other hand, selectively represented only a few of the total octasaccharide components, without any correlation to overall charge. These results indicate that the binding of PF4 to heparin occurs by relatively non-specific electrostatic interactions. The methodology delineated here may be generally useful in assessing specificity in glycosaminoglycan protein interactions. PMID- 8358153 TI - Spermatozoa-like cell invaders (nuclear vlimata) in human neoplasia. AB - Spermatozoa-like cells (nuclear vlimata) have been identified in malignant cell cultures and embryonic cells, also common in the cytology and histology of all types of human neoplasia even after chemotherapy. A new mechanism of invasion of malignant cells has been described, according to which neoplastic cells behave and function as parasites using host-cells to divide, survive and eventually produce nuclear vlimata (bullets). Nuclear vlimata are the end cell products of incomplete, unequal, assymetrical division of neoplastic cells. The nuclear vlima exhibits similar morphology to spermatozoa and virus (head with, or without, tail) and invades the cytoplasm and/or nucleus of surrounding host-cells by a similar mechanism to sperm-oocyte interaction (fertilization) or viral cell infection, in the events of nuclear vlima-->tumor-->nuclear vlima-->tumor. The nuclear vlima head contains and transfers DNA, and when incorporated into the host-nucleus is indistinguishable from nucleoli and when in the cytoplasm is similar to sperm pronucleus, observed after sperm penetration of the oocyte. Function of nuclear vlimata is directly dependent on the specific extracellular matrix produced by malignant cells, consisting of glycosaminoglycans-protease membranes. This mechanism of invasion constitutes the link of all scientific information concerning human neoplasia. PMID- 8358154 TI - A comparative immunohistochemical study of phaeochromocytomas and paragangliomas. AB - There is no definite morphological distinction between phaeochromocytomas and paragangliomas. We, therefore, attempted to determine the universality and differential utility of a panel of tumour markers for diagnosis in formalin fixed, paraffin-embedded specimens. Antibodies to neuron-specific enolase (NSE), chromogranin, synaptophysin, Leu-7, neurofilaments, cytokeratins, carcinoembryonic antigen (CEA), melanoma antigen HMB-45, S-100 protein and glial fibrillary acid protein (GFAP), were used on 11 phaeochromocytomas and 8 paragangliomas. NSE reactivity was detected in 10 phaeochromocytomas and in all paragangliomas. Chromogranin reactivity was found in all but two cases (one phaeochromocytoma and one paraganglioma). Synaptophysin reactivity was present in 10 phaeochromocytomas and in the 8 paragangliomas. Ten phaeochromocytomas stained for Leu-7, but none of the paragangliomas did. S-100-positive cells (sustentacular or type II cells) were found in 8 phaeochromocytomas and 7 paragangliomas. GFAP stained sustentacular cells of only one paraganglioma. Only in 5 phaeochromocytomas was there a focal reaction by neurofilaments. Cytokeratins, CEA and HMB-45 were never detected. We conclude that NSE, chromogranin, synaptophysin and S-100 protein are useful markers of both types of tumour, whereas GFAP staining is limited to a small number of these neoplasms. Leu-7 reactivity seems to favour diagnosis of phaeochromocytoma rather than paraganglioma, but further studies with larger series are needed to confirm this. Unlike previous reports, we did not find cytokeratin or HMB-45 immunostaining in any case. PMID- 8358155 TI - Evaluation of volume-weighted mean nuclear volume in endometrial lesions. AB - The individual nuclear size was studied in three groups of endometrial samples (simple hyperplasia -SH-, atypical hyperplasia -AH-, and well-differentiated adenocarcinoma -WDA-). The application of recent semiquantitative systems in combination with stereological methods permits a simple, quick and unbiased estimation of the volume-weighted mean nuclear volume vv(nucl). We have found an increase in the vv(nucl) from SH to AH to WDA. There are significant differences between the mean of the three groups (p < 0.01). The variance associated with estimates of vv(nucl) is mainly provided by differences among lesions; i.e. patients. This capacity for discriminating may be associated with gland and lumen endometrial quantification to improve the correct diagnosis of endometrial samples. PMID- 8358157 TI - Fibronectin expression in cancer tissues from patients undergoing radiation therapy. AB - Fibronectin expression and distribution were examined in cancer tissues from 19 patients with cancer of the head and neck regions. Samples taken before and after irradiation of approximately 10 Gy, 20 Gy or 30 Gy were analyzed by the avidin biotin-horseradish peroxidase method using mouse monoclonal antibodies against human fibronectin. The results were correlated with the patient's prognosis after radiation therapy. No remarkable changes in the fibronectin expression or distribution were found between tissue specimens taken before and after each dose of irradiation. The prognosis, however, varied according to the degree of expression and the distribution pattern of fibronectin. Seven patients in which the cancer tissue was encircled by a thick fibronectin network are still alive without recurrence 4.5-6 years after treatment, whereas 6 patients in which fibronectin was only faintly expressed or focally distributed died or developed recurrence soon after treatment. The present findings demonstrate that fibronectin expression and distribution in cancer tissue are intimately related to the patient's prognosis, and that the analysis of these two parameters is applicable as a predictive assay in radiotherapy of cancer of the head and neck regions. PMID- 8358156 TI - Ultrastructural changes induced by anabolic steroids in liver of trained rats. AB - The effects of anabolic steroid treatment in association with endurance training on biochemical serum parameters and liver ultrastructure have been investigated in male rats. Values of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were not significantly affected by administration of high doses of fluoxymesterone or methylandrostanolone. Electron microscopic examination of hepatic tissue from treated animals revealed ultrastructural alterations of hepatocytes. The most prominent changes were swelling of mitochondria, which presented electron-lucent matrix and slightly defined cristae, and a marked increase in the number of lysosomes. These changes were evident in both sedentary and trained treated rats, indicating that liver cell damage is produced by anabolic-androgenic steroids despite the simultaneous realization of physical exercise. The alterations observed were not detected by means of conventional biochemical liver tests. PMID- 8358159 TI - Fusion mechanism of the myoblasts in the myotome of the chick embryo. AB - We have studied the fusion process of myoblasts in the mytome corresponding to H.H. stages 22, 23 and 24 from calcitonin-treated chick embryos and their untreated controls. The micrograph images of this process were studied to detect the ultrastructural changes in myoblast morphology that could be associated with the known hormonal and biochemical changes that take place in preparation of fusion. Once actin and myosin myofilament differentiation and sarcomerogenesis had begun, the myotome myoblasts fused in bundles of 10-14 myoblasts, and the following was observed during this process: plasmatic membrane interdigitation and invagination; the appearance of cytoplasmic flaps covering other myoblasts and fading at the point of contact; plasmatic membranes that fade and disintegrate; membrane rupturing; double closed lamina; small ringed lamina; large disperse vesicles; small vesicles (liposomes), and semi-dense amorphous material. Seven stages were established: 1--Membrane rupture; 2--Double closed and elongated lamina; 3--Small ringed lamina aligned lengthwise; 4--Large dispersed vesicles; 5--Imprecise boundaries with amorphous material in diffuse areas; 6--Cytoplasm fusion; and 7--Prefunctional syncitium. Answers to the questions: "how", "when", "where", "why" and "for what purpose" the fusion of myoblasts takes place are suggested. PMID- 8358158 TI - Matrix changes during long-term cultivation of cartilage (organoid or high density cultures). AB - In high density (organoid or micromass) cultures of prechondrogenic mesenchymal cells from limb buds of 12-day-old mouse embryos typical cartilaginous tissue develops after 3 days. Immunomorphological investigations have shown that it contains the typical components of the cartilaginous matrix, such as collagen type II and cartilage-specific proteoglycans. After a 2-week cultivation period hypertrophic cartilage cells develop to an increasing extent. Many of these cells as well as normal chondroblasts detach from the matrix from the 2nd week in vitro onwards to assume a fibroblast-like appearance. At the same time thick (25-65 nm) collagenous fibrils occur at the surface of these cells. These thick fibrils contain collagen type I, as shown by immunomorphology. Hence, in these older cartilage cultures chondroblasts change their synthesis programme or direction of differentiation. Consequently, a model for the study of "dedifferentiation" of cartilage and possibly also transformation of cartilage cells to osteoblasts has become available. PMID- 8358160 TI - Further histological observations on popliteal lymph nodes after interruption of the afferent lymphatic vessels. AB - Lymphatic vessels afferent to the popliteal nodes in young adult rats and guinea pigs were interrupted at the lowest edge of the popliteal fossa, and regressive changes in the nodes occurring 4 to 16 or 18 weeks after surgery were re-examined histologically. In the rat, some popliteal nodes were drained by lymphatic channel(s) from the tail. After surgery, the popliteal nodes without lymphatic channel(s) from the tail underwent regression of all their constituent deep cortical units and also the peripheral cortex comprising lymph follicles, until at 18 weeks, the lymphoid organization of the node reached a minimal level. On the other hand, in popliteal nodes having a lymphatic channel from the tail, some deep cortical units and the overlying peripheral cortex underwent hypotrophy, leaving the remaining units and their overlying peripheral cortex little affected. In the guinea pig, the treated nodes underwent progressive atrophy and ultimately became rudimentary, or even vanished, after 16 weeks. Treated rudimentary nodes were composed largely of stromal cells only, and these were replaced to a various extent by fat. The present results are discussed in relation to complete and incomplete inhibition of the afferent lymph flowing into the surgically treated nodes. PMID- 8358161 TI - Nuclear morphometry lacks prognostic value in squamous cell carcinoma of the oesophagus. AB - In order to determine the possible influence in oesophageal squamous cell carcinoma of nuclear measurements on patients' postoperative survival and on various histological tumour features, we performed a nuclear morphometry study on 53 patients (50 males, 3 females) with a mean age of 57.4 years (37-79). A statistical correlation was revealed between area, perimeter and diameter and the analysis was, therefore, performed only in terms of nuclear area. No influence of nuclear area on postoperative survival was observed. Nor was a relationship found between mean nuclear area and either involvement of the oesophageal wall or degree of histological differentiation. The tumours showing expansive growth had a larger mean nuclear area than those of the infiltrative growth type, although differences did not reach statistical significance. The nuclear area standard deviation (reflecting anisocytosis of the tumour) showed no correlation with survival. In conclusion, our data do not support that measurement of nuclear parameters by static methods is of any prognostic value in surgically-treated squamous cell carcinoma of the oesophagus. PMID- 8358162 TI - Immunocytochemical distribution of serotonin and neuropeptide Y (NPY) in mouse adrenal gland. AB - By the use of immunocytochemical staining methods, we studied the morphology and distribution of 5HT and NPY immunoreactive cells and fibres in the mouse adrenal gland. The 5HT-immunoreactive cells were numerous and widely localized in the medullar tissue. These cells were arranged in three cellular types with regard to their morphological and immunocytochemical features. One of them showed cells with polygonal shape, being intensified like the typical medullary chromaffin cells. These immunoreactive cells were observed arranged in medullar islets. The second 5HT-immunoreactive cellular type was constituted by cells with polygonal shape and strong immunoreactivity. The third one was formed by cells with immunoreactive prolongations. We found some islets of chromaffin non immunoreactive cells surrounded by immunostained cells. We also observed some 5HT immunoreactive nerve fibres in the medullar tissue. NPY-like immunoreactivity was detected in both chromaffin and ganglion cells in adrenal medulla. NPY-like immunoreactivity was also detected in nerve fibres at cortical level. In a few cases, we observed medullar 5HT- and NPY-immunoreactive tissue in the adrenal cortex (monotremas). PMID- 8358163 TI - Ultrastructural alterations of the rat intestinal epithelium fed with polymeric, oligopeptidic or elementary full diet, following starvation. AB - In this study the ultrastructure of rat jejunal epithelial cells was examined, following a starvation period of 72 hours and an enteral refeeding period of 12 days, with either Nutrison, Pepti 2000, or Nutri 2000. Most changes occurred in the animals examined immediately after the 72-hour starvation period; these mainly included a significant decrease in microvilli population, occasional cell membrane disintegration, and a usual microvesicular appearance and degranulation of the rough endoplasmic reticulum. No alterations were found in the normally-fed animals (control group). This was also practically the same for the Pepti 2000 group. In the Nutrison group, a small amount of changes were found, while in the Nutri 2000 group many alterations were detected, which nevertheless were fewer than in the starved animals. The results demonstrate that the micromorphological alterations of the intestinal epithelium caused by starvation improve faster when an oligopeptidic formula is provided, which consequently results in faster and better absorption of the nutrients. PMID- 8358164 TI - Histomorphometric analysis of the reticulum of the sheep during development. AB - Histomorphometric and scanning electron microscopic analysis were performed on 74 embryos and foetuses and on 20 sheep (early post-natal to adult age). Histodifferentiation of the reticulum took place at 33 days of foetal life. Reticular ribs were observed as evaginations of the epithelial stratum germinativum at 64 days. Neutral mucopolysaccharides first appeared in epithelial cells at 46 foetal days, thereafter to decrease gradually in number, subsequently stabilising in postnatal life. Acid mucopolysaccharides, mucins and mucoid compounds were not detected. Growth curves and formulae were constructed for each tissue layer. Initial test involved multiplicative (y = axb), linear (y = a+bx) and polynomial model (y = a+b+cx2+dx3). PMID- 8358165 TI - The ileocaecal junction. AB - The ileocaecal junction remains a controversial region of the gut. There are still a lot of questions concerning its anatomical structure and function. In this review, a concise overview is given of the recent and older literature on the embryology, anatomy, including the intrinsic and extrinsic innervation, and the pharmacology of this region. Based on the available data from the literature, evidence is accumulating for a sphincteric function. PMID- 8358166 TI - Origin and differentiation of gut endocrine cells. AB - The epithelium of the digestive tract contains endocrine cells which produce serotonin and an array of regulatory peptides. It is now irrefutably established that gut endocrine cells are not of neural crest nor even of neurectodermal origin. Furthermore, the proposal that they might originate from neuroendocrine programmed epiblast has been retused by recent evidence that they share the endodermal stem cell pool with the other epithelial cells of the gut. Based on the available evidence, a working hypothesis for the differentiation of gut endocrine cells has been developed. It is proposed that initially the developing gut acquires an underlying tendency to differentiate into intestine: the endoderm has the potential to form a wide range of endocrine cell types. A little later, some influence operative over the length of the presumptive gut imposes a regionally specific pattern on the tract. This process concerns morphogenesis and pre-selection of the range and proportions of the endocrine cell types. Thereafter, the mesenchyme feeds to the endoderm confirmatory signals reinforcing this pre-selected regional pattern of endocrine cells. Once the different endocrine cell types have started to differentiate, their maturation is effected by circulating factors which include glucocorticoid hormone: this process is mediated by the mesenchyme. Other factors concerned at various stages of gut endocrine cell differentiation could be other hormones, growth factors and or components of extracellular matrix: such factors are still untested in this context. PMID- 8358167 TI - Chemocytoarchitecture of the rat locus ceruleus. AB - I shall elaborate on the cytochemical classifications of the rat locus ceruleus (LC) and state how each of these could be identified. In the LC, 80% (1,309/1,642) of the noradrenergic (NA) neurons are also GABAergic. This is found by demonstrating that two immunoreactivities coexist in adjacent sections alternately immunostained by anti-TH or anti-GABA antibody. Pharmacological manipulations with pargyline (75 mg/kg, i.p., 2 h prior to perfusion) and L tryptophan (150 mg/kg, 1.5 h prior to perfusion) revealed 5-HT-like immunoreactivity (5-HT-LI) in most LC cells (masked 5-HT cells) that produce 5-HT but not other indoleamines. If 5-HTP is applied instead of tryptophan, 5-HT-LI is shown by the raphe nuclei and a few LC cells (masked indoleamine cells) in the marginal zone. Anti-GAD antibody reveals GAD-LI in 32% of GABA neurons predominantly in the dorsal division. In situ hybridization studies detected tryptophan hydroxylase mRNA and GAD mRNA in many small- and medium-sized neurons. It is concluded that the LC consists mostly of an NA population that is possibly synthesizing multiple transmitters, such as GABA, GAD and 5-HT in single neurons so that the system enables the LC simultaneously to innervate the entire CNS. PMID- 8358168 TI - N-ethyl-N-nitrosourea-induced prenatally lethal mutations define at least two complementation groups within the embryonic ectoderm development (eed) locus in mouse chromosome 7. AB - Two loci [l(7)5Rn and l(7)6Rn] defined by N-ethyl-N-nitrosourea (ENU)-induced, prenatally lethal mutations were mapped by means of trans complementation crosses to mice carrying lethal deletions of the albino (c) locus in Chromosome (Chr) 7. Both loci were found to map to the subregion of the Mod-2-sh-1 interval that contains the eed (embryonic ectoderm development) locus, eed has been defined by the inability of embryos homozygous for certain c deletions to develop beyond the early stages of gastrulation. Evidence for at least two loci necessary for normal prenatal development, rather than one locus, that map within the eed interval came from the observation that two prenatally lethal mutations, 3354SB [l(7)5Rn3354SB] and 4234SB [l(7)6Rn4234SB], could complement each other in trans, but could not each be complemented individually by c deletions known to include the eed locus. A somewhat leaky allele of l(7)5Rn [l(7)5Rn1989SB] was also recovered, in which hemizygotes are often stillborn and homozygotes exhibit variable fitness and survival. The mapping of the loci defined by these mutations is likely to be useful for genetic, molecular, and phenotypic characterization of the eed region, and mutations at either locus (or both loci) may contribute to the eed phenotype. PMID- 8358169 TI - A new Pax gene, Pax-9, maps to mouse chromosome 12. AB - Members of the Pax gene family have recently been shown to play important roles in mouse embryogenesis. Of eight so far characterized Pax genes, three have been associated with mouse developmental mutants. Here we report the cloning of a new Pax gene, Pax-9. Most of the DNA sequence encoding the highly conserved paired domain has been determined and compared with previously known paired domains. This comparison classifies Pax-9 as a member of the same subgroup as Pax 1/undulated. By analysis of the segregation of a Pax-9 restriction fragment length polymorphism and a large number of simple sequence length polymorphisms in an interspecific C57BL/6 x Mus musculus mollosinus backcross, Pax-9 was mapped close to the D12Nds1 locus on the proximal part of Chromosome (Chr) 12. PMID- 8358170 TI - Genome mapping by arbitrary amplification of yeast artificial chromosomes. AB - Several methods have been described for using the polymerase chain reaction (PCR) to isolate fragments of DNA for genome mapping. We have developed an approach for isolating discrete fragments by amplifying DNA with single oligonucleotides (10 mers) with arbitrarily selected sequences. The method is rapid and technically simple. We isolated fragments from a contig of three yeast artificial chromosomes (YACs) from the human Xq28 chromosomal region. We purified YACs yWXD37, yWXD348, and yWXD705 from a preparative pulsed field gel. Amplifications of each YAC were performed with single 10-mers as the PCR primers and the products were visualized on agarose gels. These fragments have been successfully used as hybridization probes against Southern blots containing the YACs and against blots containing human genomic DNA and somatic cell hybrids containing Xq28 as their only human constituent. The results have been concordant with the known order of the YACs. We have also successfully combined 10-mers with primers derived from vector arm sequences to isolate YAC ends. We discuss several uses of this method in comparative mapping and in filling in gaps in physical and genetic maps. PMID- 8358171 TI - The positions of 12 simple sequence repeat markers relative to reference loci on mouse chromosome 16. AB - The genetic map positions of 12 simple sequence repeat (SSR) markers spanning mouse Chromosome (Chr) 16 were determined relative to reference markers on that chromosome. Interval mapping data were obtained with a panel of DNAs from two intersubspecific backcrosses. All but one of the markers were typed by us of nonradioactive polymerase chain reaction (PCR) products analyzed on agarose gels. The marker order was determined to be Prm-1, D16Mit9, Igl-1, D16Mit29, D16Mit1/D16Mit2, Smst, D16Mit4, D16Mit11, Gap43, D16Mit14, D16Mit30, D16Mit5, Pit 1, D16Mit27, D16H21S16 (formerly D21S16h), D16Mit19, App, D16Mit7, Sod-1. Two of these markers mapped to the known human Chr 21 (HSA21)/Chr 16 conserved linkage group. Nine additional SSR markers could not be typed because they were not polymorphic (four markers), did not amplify MOLD/Rk DNA (three markers), or failed to give PCR products under a range of conditions (two markers). A subset of the most robust SSRs provide a useful marker set for the analysis of previously unmapped crosses. PMID- 8358173 TI - Construction of a large-insert yeast artificial chromosome library of the mouse genome. PMID- 8358172 TI - Chromosomal localization of HSP70 genes in cattle. AB - Five genomic clones representing three HSP70 genes of cattle were biotin labeled and independently hybridized to cattle chromosomes. Fluorescence in situ hybridization localized HSP70-2 to Chromosome (Chr) 23 band 22 (the BoLA region), HSP70-3 to Chr 10 band 34, and HSP70-4 to Chr 3 band 13. Since HSP70-1, a fourth HSP70 gene, is tightly linked with HSP70-2 and the BOLA, HSP70-1 was also localized to Chr 23 band 22. The localization of HSP70-4 is the first assignment of a cattle U6 marker; thus, this entire syntenic group is tentatively placed in cattle Chr 3. PMID- 8358174 TI - Striking conservation of the brain-specific region of the dystrophin gene. PMID- 8358176 TI - Localization of the inhibin beta B gene on mouse chromosome 1. PMID- 8358175 TI - The serotonin 5-HT1B receptor subtype (Htr1b) gene maps to mouse chromosome 9. PMID- 8358177 TI - Emk, a protein kinase with homologs in yeast maps to mouse chromosome 19. PMID- 8358178 TI - Cell adhesion molecules and potential for pharmacological intervention in lung inflammation. PMID- 8358179 TI - Heterogeneity of guinea-pig lung muscarinic receptors revealed by [3H]4-DAMP binding. AB - Muscarinic receptors present in guinea-pig lung were characterized using the M3 selective radioligand [3H]4-diphenylacetoxy-N-methyl-piperidine methiodide ([3H]4 DAMP). In saturation studies, [3H]4-DAMP identified two populations of binding sites with approximately 4% of the sites displaying high affinity (Kd = 0.21 nM and Bmax = 10 fmol/mg prot.) while the remaining sites were low affinity ones (Kd = 18.11 nM and Bmax = 269 fmol/mg prot.). In competition studies with [3H]4-DAMP (0.35 nM), methoctramine and hexahydro-siladifenidol (HHSiD) identified 50 and 70% of high affinity binding sites displaying the pharmacological profile of the M2 and the M3 receptors, respectively. No evidence was found for high affinity [3H]pirenzepine binding sites in guinea-pig lung. However, pirenzepine/[3H]4-DAMP competition experiments suggested that pirenzepine recognized an equal proportion of [3H]4-DAMP binding sites with intermediate and low affinity binding constants. The intermediate affinity binding constant was inconsistent with the presence of M1 receptors and reflected more the presence of M4 or a mixture of M3 and M4 receptors. The low affinity pirenzepine binding sites may represent M2 receptors. These results provide further evidence for the occurrence of M2 and M3 receptors and suggest the presence of the M4 muscarinic receptor subtype in guinea-pig lung. PMID- 8358180 TI - The protective effect of inhaled levomepromazine (Nozinan) on histamine-induced bronchial constriction. AB - The effect of inhaled levomepromazine (Nozinan, Veractil) on bronchial responsiveness to inhaled histamine was investigated in asthmatics. In a double blind, randomized controlled study, 12 asthmatics (FEV1% pred 52-96%, and PC20 histamine 1.01 mg/ml (geometric mean)) were challenged before and after inhalation of levomepromazine in three different doses. Before and after each inhalation of levomepromazine, PC20, FEV1, the continuous reaction time (CRT) and the subjective sedation score (VAS) were determined. A dose-dependent increase in PC20 was observed after inhalation of levomepromazine. PC20 was increased by up to 4.02 two-fold concentration differences (doubling), i.e. up to a 38-fold increase from the basic values. Inhalation of the two higher doses of levomepromazine had a small sedative effect evaluated from an increase in CRT and the VAS-score and corresponding to the plasma concentrations. We conclude that inhaled levomepromazine has a dose-dependent protective effect on histamine induced bronchial hyperresponsiveness in asthmatics and that inhalation of levomepromazine was well tolerated. The mechanism by which levomepromazine acts on histamine-induced bronchial hyperresponsiveness is not known but it could be partly explained by the antihistaminic effect. In this respect levomepromazine bears comparison with the most potent second generation antihistamines. The plasma concentrations of levomepromazine measured corresponded to those seen after oral intake of 5-10 mg levomepromazine. PMID- 8358182 TI - Effects of melatonin on isolated pulmonary artery and vein: role of the vascular endothelium. AB - The influence of melatonin on tension of isolated pulmonary vascular smooth muscle rings was examined in these experiments. Melatonin caused a dose-dependent relaxation of precontracted (30 mM KCl) pulmonary artery and pulmonary vein. Removal of the endothelium did not alter the relaxant response to melatonin in pulmonary artery. In pulmonary artery with endothelium intact, preincubation with indomethacin, but not L-NG-monomethyl-L-arginine (L-NMMA) or deferoxamine, antagonized the relaxant response to melatonin. In pulmonary artery with endothelium removed, preincubation with deferoxamine, but not indomethacin, phorbol esters, or lithium chloride, antagonized the relaxant response to melatonin. In pulmonary vein, removal of the endothelium significantly increased the maximum relaxation attained in response to melatonin. In pulmonary vein with endothelium intact, preincubation with indomethacin, but not L-NMMA or deferoxamine, antagonized the relaxant response to melatonin. On the other hand, preincubation of de-endothelialized pulmonary vein with lithium chloride significantly increased the relaxation response to melatonin. These experiments demonstrate that both pulmonary artery and vein relax in response to melatonin and the mechanisms are apparently different. PMID- 8358181 TI - The effects of indomethacin and thiorphan on bradykinin-induced albumin output and submucosal gland secretion in the ferret trachea in vivo. AB - In the ferret liquid-filled trachea in vivo, intraluminal bradykinin (BK, 3-300 microM) produced concentration-dependent increases in the output of lysozyme from submucosal gland serous cells and albumin movement into the lumen. Baseline outputs of albumin and lysozyme were not altered significantly by intraluminal indomethacin (10 microM) or thiorphan (10 microM). However, intraluminal indomethacin completely blocked the BK-induced increase in albumin output. Intraluminal thiorphan (10 microM) did not significantly potentiate BK-induced albumin output, although mean output was higher. Neither indomethacin nor thiorphan significantly altered BK-induced lysozyme output, although mean output was reduced in the presence of indomethacin. Thus BK increases albumin output and may increase lysozyme output via the action of cyclooxygenase products. Inhibition of neutral endopeptidase activity may enhance the action of BK on albumin output. PMID- 8358183 TI - Effects of loop diuretics on airways and inflammatory cells both in vivo and in vitro. PMID- 8358184 TI - New perspectives in the pulmonary circulation and hypoxic pulmonary vasoconstriction. AB - In the past few years there has been a reawakening of interest in the systems that underly pulmonary vascular control and an increased awareness of the clinical potential of pharmacological manipulation of the pulmonary circulation. Nevertheless, although so much has been learned about the physiological role of the endothelium, vasoactive substances, and neural modulation of the pulmonary vasculature; how these disparate influences interact to control the matching of ventilation to perfusion remains uncertain. Consequently, even less is known of the way in which lung injury influences these regulatory processes. It is likely that the response to hypoxia may involve a system with many pathways and much redundancy, such that blockade of the production of a single agent has only a minor effect on HPV. We speculate that the products of arachidonic acid metabolism, PAF, adenosine and EDRF, may act in concert with neural pathways in a 'microenvironment' bounded by the alveolus and endothelium to modify pulmonary vascular tone during both normoxic and hypoxic conditions. PMID- 8358185 TI - [Increase in infections caused by Salmonella enteritidis--causes and possibilities for intervention]. AB - Recently published data document a worldwide increase of infections of humans and of food contamination by Salmonella enteritidis (SE). The results of our own analyses of animal foods reflect this general trend and indicate a clonal spreading of SE phage type (PT) 4 in animal foods in Northern Bavaria. In humans SE PT 4 shows high invasivity and virulence. In poultry an adaption of certain SE phage types is supposed to have taken place. Those types cause infections of poultry flocks without visible symptoms. Hens do lay eggs during infection, but 1.5-2.0% of them are SE contaminated. Incorrect handling and incorrect processing and use of SE infected hens' eggs and/or of foods prepared with those eggs have caused a great number of infections in humans. The present state of scientific research leads us to assume that the increase in human SE infections is linked to the increase of the SE infections of poultry and hens' eggs. In order to stem further spreading of SE and to improve the protection of the consumer certain measures have to be taken in original/primary production, production and processing of poultry meat and eggs and in handling of eggs in commercial and private kitchens. These measures, which, from a veterinary point of view, should be surveyed and also be taken by the relevant authorities, are described in 5 lists. PMID- 8358186 TI - [Timely consultation of psychiatric assessment by members of the public health services]. AB - The present possibilities and limitations of psychiatric expertising (supplementary or main) by the Public Health services are explained taking the proband group of public servants as an example. The need, preconditions, planning, designing, interaction, methods, amount of work and cost involved in such expertising are described in detail and illustrated by brief case reports, including psychodynamic aspects and definition and outlining of various phases of the relevant examinations. A guiding thesis is proposed: Successful psychiatric assessment of an individual is always also a crisis intervention with therapeutic changes and effects--even if this aim has not been consciously aimed at, but better still if performed with this purpose in mind. Obsolete approaches are pinpointed and quality standards stipulated. Possibilities of improvement and preventive aspects are shown. PMID- 8358187 TI - [Results of breast milk examinations in Northern Bavaria]. AB - During the years of 1984-1991 2069 samples of human milk from Northern Bavarian were analyzed for residues of organochlorined pesticides and polychlorined biphenyls. In this paper it is exclusively reported about substance residues in human milk which were toxicological valuated by the German Research Fellowship (Deutsche Forschungsgemeinschaft). Concerning the amount of pesticides and PCB residues in human milk a dependence to woman's age, number of children and time of suckle period could be found. There was not seen any dependence to kind of nutrition and smoking behavior. Residue-concentrations of forbidden organochlorined pesticides decrease during the whole research period. Nevertheless polychlorined biphenyls will continual regarded as critical substances where no decreasing of residue concentrations is observed. This substance class furthermore will be observed because of continual environment pollution. It is reported about a test in which during a suckle period milk of two women was analyzed after weekly sampling. After ten weeks significantly decreasing of residue amounts concerning the most observed substances were found. A conclusion to help in practical counsel for nursing mothers is given. PMID- 8358188 TI - [Data on the status of the organizational structures of hospital hygiene in Germany. II--Rehabilitation clinics, psychiatric hospitals]. AB - The results of an inquiry about the personnel and organisation of the hospital hygiene in 657 German rehabilitation centres and psychiatric hospitals demonstrate that 24% of these hospitals have a hospital epidemiologist, 44% have infection control nurses and 74% infection control physicians. Infection control committees are present in 64% of these hospitals. 78% of the hospitals use the guideline of the Federal Public Health Office "On the Identification, Prevention and Control of Hospital Infections" as a basis for all decisions on hospital hygiene. PMID- 8358189 TI - [Hydrophobizing building facades and subsequent indoor air pollution and offensive odors--10 case reports]. AB - Water repellent and facade protective solvent-containing agents applied to external facades (hydrophobizing) may in some cases cause considerable and long term indoor aerosol pollution with aliphatic and aromatic hydrocarbons. This may result in odor nuisance and other complaints that may even make the affected rooms uninhabitable. To date the entire phenomenon has not been subjected to conclusive scientific research although its existence has long been known. Administrative offices react inconsistently to complaints; in many cases their actions are unsystematic and they try to minimize the issue. Measurement data and results of investigations from 10 practical cases are juxtaposed to find causal links and to assess the relevance of the entire problem of hydrophobizing of facades. The type, extent and duration of indoor aerosol pollutions are discussed and assessed in respect of already existing guiding and reference values. Furthermore, suggestions are made to the Public Health Services in the sense of preventive health protection. A more far-reaching consequence would be to introduce a licence for facade hydrophobizing or weather-proofing of buildings; this suggestion is offered for discussion. PMID- 8358190 TI - [Heavy metal pollution of soil and garden products of Stolberg home gardens and lead and cadmium pollution of small farms in Stolberg]. AB - Cadmium, lead and zinc were determined in garden soils and vegetable products from private gardens located in a lead/zinc smelter area (Stolberg, Germany). At the same time lead and cadmium were measured in blood and urine samples collected from 90 garden owners. Inspite of extraordinary high levels of cadmium and lead in garden soils and vegetables, blood lead, blood cadmium and urine cadmium levels were not or only slightly elevated in the gardeners when compared to a reference group of subjects from the same area who did not consume home-grown vegetables and fruits. The results show that high levels of pollutants in soil and vegetables are not necessarily associated with an increased burden of pollutants in the human body, and that the transfer of pollutants from soil to humans might have been overestimated in some cases. Moreover, the results underline the preventive character of the guideline values presently applied with respect to the evaluation of soil contaminants. PMID- 8358191 TI - [Possibilities of quality assurance in ambulatory rehabilitation]. AB - Formal, structurally determined quality requirements (for medical and non-medical staff, space and equipment, respectively) are supplemented by guidelines that are able to inform about the actual course of rehabilitation. Not only externally controlled medical reports on the treatment are suited for this, but also inquiries of patients comparisons between sickness insurances (for example on duration of inability to work, need for hospital measures of rehabilitation) and the comparison with patients who did not take part in ambulant rehabilitation. A report system has to be built up that pictures the clientele of the "reha" institution, measures changes and documents results a long-term basis. The proposed periodical tests and final test serve not only for the control of patient progress in each single case with information for the practitioner, but also give financial committees hints on the efficiency of the work of the institutions for rehabilitation. Continuous attendance is proposed with a report system and scientific evaluation, whose results are sent concisely but anonymous by to the contract partners on a quarterly basis. A committee for quality assurance discusses new developments and improves ambulant rehabilitation. PMID- 8358192 TI - Demonstration of nucleolar organizer regions in lung carcinoma by silver staining. AB - Nucleolar organizer regions (NORs) were investigated in lung carcinomas by silver staining. This method was applied to 111 lung carcinoma specimens, including 40 with squamous cell carcinoma (SCC), 42 with adenocarcinoma (ADENO), 8 with adenosquamous carcinoma (ADESQ), 8 with small cell carcinoma (SMCC), 6 with large cell carcinoma (LGCC), and 7 with typical carcinoid tumors (CAOID). The mean AgNOR counts of ADENO, SCC, ADESQ, SMCC, and LGCC were significantly higher than those of the normal bronchial surface and those of the glandular or alveolar epithelium. The mean AgNOR count of CAOID was significantly higher than those of the normal glandular and alveolar epithelium but not that of the surface epithelium. The mean AgNOR count of SCC was significantly higher than that of bronchial squamous metaplasia, and the count of SMCC was significantly higher than that of CAOID. Within the same cancer category, the mean number of AgNORs increased in parallel with the histological tumor grades. These results indicate that the AgNOR method is useful for differentiating lung carcinoma from its normal counterparts and for evaluating histological tumor grades in the same lineage of lung carcinoma. PMID- 8358193 TI - Elevation of carcinoembryonic antigen related to biliary malignancy in hepatolithiasis. AB - Bile duct neoplasms occur relatively often in patients with hepatolithiasis in Taiwan. In this study, 49 patients with a positive immunoperoxidase stain for carcinoembryonic antigen (CEA) in the bile duct glands were examined in relation to the concentration of CEA in serum and bile. The bile concentrations of CEA in 15 control patients, 16 patients with hepatolithiasis only, 7 with hepatolithiasis and bile duct carcinoma, and 11 with bile duct carcinoma only were 4.09 +/- 4.12, 70.49 +/- 81.62, 137.73 +/- 66.15, and 144.3 +/- 117.31 ng/ml (mean +/- SD), respectively. A positive CEA stain from the bile duct was seen in 13.33%, 81.23%, 85.71%, and 90.91% of each group, respectively. No strongly positive staining, (2+ or 3+) was found in the control group, but it was found frequently in the hepatolithiasis and bile duct carcinoma groups. The findings of this study therefore suggest the probability of a combined neoplasm in patients with hepatolithiasis if the CEA value is unusually elevated in the serum or bile. PMID- 8358194 TI - Surgery for cholelithiasis in cirrhotic patients. AB - Although biliary tract surgery for cholelithiasis is performed frequently in Japan, cirrhotic patients require special consideration. Postoperative complications after biliary tract surgery were studied in 23 patients with liver cirrhosis and associated cholelithiasis, 9 of whom had no complications, 8 had minor complications, and 6 had severe complications. Concerning the relation between Child's classification and postoperative complications, no complications were seen in four Child's type A patients, but seven of ten (70%) Child's type B patients and seven of nine (78%) Child's type C patients developed complications. Two (20%) of the Child's type B patients and four (44%) of the Child's type C were severe, and three of the latter group died. Regarding the preoperative laboratory findings, significant differences were seen between the patients without complications and those with severe complications in serum bilirubin, albumin, and ICG R15 values. Of the six patients with severe complications, five had choledocholithiasis, three of whom died of liver failure, while two developed biliary peritonitis caused by insufficient fistula formation after removal of the T-tube. Thus, for the treatment of choledocholithiasis in patients with severe cirrhosis, avoiding surgical invasion through the use of such techniques as endoscopic papillotomy is recommended whenever possible. PMID- 8358195 TI - The reticuloendothelial system and hepatocyte function in orthotopic liver transplantation. AB - The reticuloendothelial system function, especially phagocytic activity, and hepatocyte function were investigated in dogs undergoing an orthotopic liver transplantation. The donor's phagocytic index, measured by a lipid emulsion test, was higher in the Survivor group which survived more than 3 days after transplantation (0.063 +/- 0.008 vs 0.024 +/- 0.002; mean +/- standard error of the mean (SEM), P < 0.01). There was a statistically significant difference in the phagocytic index between the survivor and nonsurvivor groups. However, the hepatocyte function at an early phase after transplantation, indicated by the arterial ketone body ratio, hepaplastin test and lecithin cholesterol acyltransferase level, did not distinguish the Survivor group from the Nonsurvivor group at all. In the survivor group, the hepaplastin test and the lecithin cholesterol acyltransferase level were significantly decreased after liver transplantation, namely from 155 +/- 15% to 58 +/- 5% and from 57 +/- 12 unit/ml to 19 +/- 1 unit/ml on the 2nd day after transplantation (P < 0.01, P < 0.05), respectively. On the other hand, the reticuloendothelial system (RES) function, as estimated by the phagocytic index and serum complement activity (CH 50), demonstrated no change throughout the experimental period. The present study therefore demonstrated that the operative results might be affected by the phagocytic activity. PMID- 8358197 TI - An unusual cause of hydropic gallbladder and biliary colic--heterotopic pancreatic tissue in the cystic duct: report of a case and review of the literature. AB - We present herein an unusual case of heterotopic pancreas in the cystic duct with hydrops of the gallbladder and concomitant chronic pancreatitis of the heterotopic tissue. A review of the relevant literature is discussed following the presentation of this case. PMID- 8358196 TI - Suppressive effect of doxorubicin on liver recurrence after resection of colonic VX2 cancer lesions: difference in efficacy according to the injection protocol. AB - An animal model with liver cancer recurrence was induced by resecting colonic VX2 cancer lesions in 57 rabbits, and the effects of doxorubicin (ADR) on the recurrence were examined. Animals were divided into a control group and three chemotherapeutic groups: a portal injection group, to which ADR was injected into the portal vein after resection of the primary lesions; a peripheral injection group, to which ADR was injected into a peripheral vein after resection; and a preoperative injection group, to which an ADR dose of 0.5 mg/kg was peripherally injected 0, 1, and 2 days prior to resection followed by a portal injection of ADR 0.5 mg/kg after resection. The rate of liver recurrence was 100% in the control group, whereas it was 0% and 60% in the portal ADR 1.0 and 0.5 mg/kg injection groups, and 60% and 100% in the peripheral ADR 1.0 and 0.5 mg/kg injection groups. In the preoperative group, the rate was 0%, 100%, and 67% in the animals injected 2, 1, and 0 days prior to resection, respectively. These results suggest that portal injection or appropriate combinations of preoperative peripheral and portal injections of ADR are more effective than peripheral or portal injection alone in the suppression of liver recurrence. PMID- 8358198 TI - Bilateral femoral nerve compression by iliacus hematomas complicating anticoagulant therapy. AB - An unusual case of bilateral femoral nerve compression caused by iliacus hematomas in a patient on anticoagulant therapy is herein reported with special reference to the comparative diagnostic value of ultrasonography, computerized tomorgraphy, and magnetic resonance imaging. The importance of early surgical decompression is also emphasized. PMID- 8358199 TI - An infant with bilateral adrenal neuroblastoma found by mass-screening: report of a case. AB - A male infant with bilateral adrenal neuroblastoma found by mass-screening is herein reported. The patient presented with almost equal-sized tumors, each remaining confined to the respective adrenal gland without crossing the midline. No other tumorous lesion was evident. The two adrenal tumors had similar histologic features and appeared to have grown concurrently. Such simultaneous occurrence of primary adrenal neuroblastoma is unusual, and appears to reflect the multicentric origin of this tumor. PMID- 8358200 TI - A solid and papillary (solid-cystic) tumor of the pancreas occurring in a 36-year old man: report of a case. AB - A case of a solid and papillary (solid-cystic) tumor of the pancreas occurring in a 36-year-old man is herein reported. This patient was admitted with left hypochondrial pain and diagnostic imaging detected a large tumor consisting of both solid and cystic components in the tail of the pancreas. A distal pancreatectomy with splenectomy was performed. The resected tumor was diagnosed as a solid and papillary tumor of the pancreas by pathological examination. Detailed immunohistochemical studies showed that the tumor consisted of cells both exocrine and endocrine in character. Thus, this case appears interesting from the point of cellular differentiation in solid and papillary tumors, since they are generally considered to have an acinar cell origin. PMID- 8358201 TI - Intussusception caused by a carcinoma of the cecum during pregnancy: report of a case and review of the literature. AB - A case of intussusception due to a carcinoma of the cecum during pregnancy is reported. A 27-year-old pregnant female was admitted to Shimodate Municipal Hospital because of abdominal pain, nausea and vomiting. Her abdomen was distended, and a relatively hard mass was palpable in the right hypochondrium. Following a diagnosis of intussusception by ultrasonography, a laparotomy was performed. The lesion causing the intussusception was found to be a carcinoma of the cecum, and thus a right hemicolectomy with lymph node dissection was carried out. Histological examination revealed that the tumor was a well-differentiated adenocarcinoma which had invaded the muscularis propria but was superficial to the subserosa. None of the lymph nodes were cancerous. The incidence of colonic cancer above the peritoneal reflection during pregnancy is very low. Only 24 cases have been previously reported; our patient is only the 25th case, as well as being the first case demonstrating Dukes' A. Due to the intussusception, ultrasonography was effective for diagnosis and the patient was able to undergo a curative operation at an earlier stage than other patients. PMID- 8358202 TI - Carcinosarcoma of the esophagus: a report of two cases. AB - Among 137 cases of esophageal neoplasms surgically treated at Kobe City General Hospital from 1983 to 1990, there were two patients with a huge polypoid lesion identified as carcinosarcoma by light microscopic examination, both of whom underwent radical resection and esophagogastrostomy. Microscopic examination of the resected specimens revealed the tumors to be composed of carcinomatous and sarcomatous elements. Additional immunohistochemical examination disclosed keratin-positive cells in the carcinomatous element and vimentin-positive cells in the sarcomatous element. In case 1, keratin-positive cells were also found in the sarcomatous element, which suggested that the sarcomatous cells were derived from epithelial cells. Despite the huge size of the tumors, the depth of invasion to the esophageal wall was limited to the mucosal layer in case 1 and the submucosal layer in case 2, and there has been no evidence of recurrence in either case since surgery. PMID- 8358203 TI - Effect of superoxide dismutase, allopurinol and glucocorticoids on liver and lung metallothionein induction by endotoxin in the rat. AB - Liver and lung metallothionein (MT) levels were increased by endotoxin. The administration of superoxide dismutase (SOD) or allopurinol (ALLO) before (30-60 min) or after (24-32 h) the endotoxin treatment either increased or did not affect the effect of endotoxin on MT levels, depending on the particular treatment and tissue. SOD and ALLO also increased liver and lung MT levels in control rats. In contrast, liver MT levels tended to be decreased by the glucocorticoid prednisolone (PRED) when administered before the endotoxin and were significantly decreased when it was administered after endotoxin. The effect of PRED on lung MT levels was completely different, since it decreased the effect of endotoxin when injected before the lipopolysaccharide, but increased it when injected after the endotoxin. Liver lipid peroxidation, as measured by thiobarbituric acid reactants (TBARs), increased after endotoxin in the liver but not in the lung, an effect even potentiated in some cases by the antioxidants studied. As expected, tissue MT and TBARs could not be correlated. PMID- 8358204 TI - Ferric reductases of Legionella pneumophila. AB - Ferric reductase enzymes requiring a reductant for maximal activity were purified from the cytoplasmic and periplasmic fractions of avirulent and virulent Legionella pneumophila. The cytoplasmic and periplasmic enzymes are inhibited by zinc sulfate, constitutive and active under aerobic or anaerobic conditions. However, the periplasmic and cytoplasmic reductases are two distinct enzymes as shown by their molecular weights, specific activities, reductant specificities and other characteristics. The molecular weights of the cytoplasmic and periplasmic ferric reductases are approximately 38 and 25 kDa, respectively. The periplasmic reductase (Km = 7.0 microM) has a greater specific activity and twice the affinity for ferric citrate as the cytoplasmic enzyme (Km = 15.3 microM). Glutathione serves as the optimum reductant for the periplasmic reductase, but is inactive for the cytoplasmic enzyme. In contrast, NADPH is the optimum reductant for the cytoplasmic enzyme. Ferric reductases of avirulent cells show a 2-fold increase in their activities when NADPH is used as a reductant in comparison with NADH. In contrast, ferric reductases from virulent cells demonstrated an equivalent activity with NADH or NADPH as reductants. With the exception of their response to NADPH, the ferric reductase at each respective location appears to be similar for avirulent and virulent cells. PMID- 8358205 TI - Intestinal administration of copper and its transient release into venous rat blood serum concomitantly with metallothionein. AB - The molecular side of copper transport in biological systems is unknown. It was attempted to examine the copper and metallothionein (MT) release into the portal blood in rats in vivo. After direct administration of Cu(II) into the jejunum the copper and MT levels were distinctively higher in the portal venous serum compared with that of the vena cava inferior. MT in gel filtrated serum samples was analyzed immunologically employing ELISA and a monoclonal antibody to rat MT I. Affinity chromatography on Protein A-Sepharose resulted in a higher immunoreactivity in the portal compartment as deduced from an elevated MT antibody complex. It is assumed that MT serves as a genuine transport system for cuprous copper during the mucosal-to-serosal flux of this biologically important transition metal. PMID- 8358206 TI - Indirect utilization of the phytosiderophore mugineic acid as an iron source to rhizosphere fluorescent Pseudomonas. AB - The phytosiderophore mugineic acid (MA) was studied as a source of iron for rhizosphere fluorescent pseudomonads. 55Fe supplied as Fe-MA was taken up by Pseudomonas putida WCS358, B10 and St3 grown under iron deficient conditions. The uptake decreased when the bacteria were grown in the presence of iron. However, no differences in uptake were observed when a siderophore deficient mutant was tested. Since ligand exchange between pseudobactin and MA was shown to occur rapidly with a half-life of 2 h, MA mediated iron uptake probably proceeds through this indirect mechanism. The ecological implications of these findings are discussed. PMID- 8358207 TI - Influence of dietary iron deficiency on acute metal intoxication. AB - The influence of dietary iron deficiency on acute nickel, lead or cadmium toxicity as reflected by the induction of hepatic, renal and intestinal metallothionein (MT), disposition of the metals, and alterations in hematological parameters was investigated in rats. The administration of cadmium induced the hepatic, renal and intestinal MT while that of nickel or lead induced hepatic MT only. However, dietary iron deficiency did not influence the cadmium induced tissue MT but enhanced the ability of nickel or lead to restore the normal synthesis of renal and intestinal MT lowered under the influence of reduced body iron status. The accumulation of lead in liver and kidney and that of cadmium enhanced in liver only, while tissue deposition of nickel remained unaffected by iron deficiency. The induction of hepatic MT by three metals appears related to the concomitant rise in the hepatic zinc, calcium and iron levels in normal rats. However, dietary iron deficiency increased the hepatic zinc in response to nickel or cadmium and that of heptic calcium in response to lead. PMID- 8358208 TI - Involvement of metallothionein and copper in cell proliferation. AB - Metallothionein is a low-molecular weight, cysteine-rich, metal-binding protein which has been implicated in the detoxification of toxic metals (cadmium, mercury), metabolism of zinc and copper, as well as in the scavenging of free radicals. Recent evidence suggests that the protein may also be involved in cell proliferation. Based on the experiments carried out so far, it is assumed that the fundamental role of metallothionein in cell proliferation may be to detoxify and/or transfer copper ions from the cytoplasm to the nucleus at the G1/S phase, which in turn participate in some way in nuclear DNA synthesis. PMID- 8358209 TI - The effect of lead on iron uptake from transferrin in human erythroleukemia (K562) cells. AB - The effect of lead on cellular iron metabolism has been investigated using human erythroleukemia (K562) cells. When the cells were cultured with 100 microM Pb2+ for 48 h, the rate of cellular iron uptake from transferrin decreased to 46% of that in untreated cells. Scatchard analysis of the binding data revealed that this reduction was the result of a decrease in the number of transferrin receptors rather than an alteration in ligand-receptor affinity. The results of immunoprecipitation of transferrin receptors on the cell surface also confirmed the decreased expression of transferrin receptors by lead-treated cells. The down regulation of transferrin receptors by treatment with lead did not result from a decrease in the total amount of the receptor, as determined by immunoblotting. Moreover, the biosynthesis of the receptor was unaffected by lead treatment. Thus, the down-regulation of surface transferrin receptors in lead-treated cells might be due to a redistribution of receptors rather than an actual loss of receptors from the cell. Using kinetic analysis, it was shown that redistribution of the receptor did not result from the alteration in the rates of transferrin receptor recycling. A comparison of the amounts of transferrin receptor on the cell surface and in the cycling pool revealed that the sequestration of the receptor from normal flow through the cycle might cause down-regulation of the surface receptor. PMID- 8358210 TI - Zinc affects siderophore-mediated high affinity iron uptake systems in the rhizosphere Pseudomonas aeruginosa 7NSK2. AB - Zinc concentrations ranging between 0.1 and 1 mM only slightly reduced maximal growth of wild-type Pseudomonas aeruginosa 7NSK2 in iron-limiting casamino acid medium, but had a clear negative effect on the growth of mutant MPFM1 (pyoverdin negative) and especially mutant KMPCH (pyoverdin and pyochelin negative). Production of pyoverdin by wild-type strain 7NSK2 was significantly increased in the presence of 0.5 mM zinc and could not be repressed by iron even at a concentration of 100 microM. Siderophore detection via isoelectrofocusing revealed that mutant KMPCH did not produce any siderophores, while mutant MPFM1 overproduced a siderophore with an acidic isoelectric point, most likely pyochelin. Pyochelin production by MPFM1 was stimulated by the presence of zinc in a similar way as pyoverdin for the wild-type. Analysis of outer membrane proteins revealed that three iron regulated outer membrane proteins (IROMPs) (90, 85 and 75 kDa) were induced by iron deficiency in the wild-type, while mutants were found to have altered IROMP profiles. Zinc specifically enhanced the production of a 85 kDa IROMP in 7NSK2, a 75 kDa IROMP in MPFM1 and a 90 kDa IROMP in KMPCH. PMID- 8358211 TI - [Biliary cystadenoma]. AB - Biliary cystadenomas are rare biliary ductal neoplasms of congenital origin. There is an excellent correlation between CT and sonographic findings for number, size and location of the lesions. However, sonography can demonstrate better morphologic features such as thickened wall, mural nodules and septations. CT shows more clearly the accurate size and location of the neoplasm to surrounding structures. Angiography is not diagnostic; however, it can help to distinguish between benign and malignant lesions. MRI provides useful information for surgical planning, demonstrating well the relationship of the tumor to vascular structures and other organ systems. Complete excision is the treatment of choice to prevent recurrence or malignant transformation of biliary cystadenomas. PMID- 8358212 TI - Stereo-microvision. Development of an opto-electronic operating microscope. AB - A novel opto-electronic operating microscope has been designed and clinically tested. It consists of a small camera microscope, a central electronic unit, and a stereoscopic video monitor. Advanced miniaturization permitted ergonomics superior to those of conventional optomechanical microscopes. Electronic imaging facilitates coupling to an ultrasound navigation system which enables the neurosurgeon to verify the location of the focus in real time, correlated with CT and MRI pictures. A fully computerized, digital operating microscope will now be developed based on this prototype. PMID- 8358213 TI - Current status of the imaging modalities in the pre- and postoperative diagnostic workup of liver transplant patients. AB - Before transplantation, imaging procedures are mainly used to exclude factors which may serve as contraindications, render surgery difficult, or necessitate a modification of the operative technique. In addition, assessment of liver volume is necessary before segmental liver transplantation. Sonography or other cross sectional imaging modalities are sufficient for these purposes. After transplantation, imaging is principally required in cases with suspected complications. Sonography, including Duplex and Doppler sonography, is an excellent first investigative modality for this purpose in addition to assessment of the clinical and biochemical parameters. Sonography can diagnose not only vascular complications but also biliary and infective complications; the former may also be a concealed cause of the latter. In unclear infections sonography often has to be supplemented by other modalities like CT. In equivocal cases a puncture is indicated. Invasive procedures are necessary in only selected cases, in particular when an intervention is under consideration. At present MR plays a limited role in the diagnostic workup as it rarely offers additional information except in very few cases. The early diagnosis of rejection cannot be reliably made by any of the imaging modalities and is essentially dependent on the biopsy. PMID- 8358215 TI - [Dialysis-associated amyloidosis. Part 2: Incidence and site of osseous amyloidosis. Dialysis characteristics and clinical findings]. AB - In a conventional radiographic skeletal survey of 90 hemodialyzed patients, 28% (25 patients) showed renal osteopathy; 27 patients (30%) had periarticular bone cysts and 3 patients (3%) presented radiological evidence of destructive spondylarthropathy. The bone cysts were most commonly identified in the carpal bones and around the hips and shoulders; destructive spondylarthropathy was seen in the cervical and lumbar spine. Whereas characteristic radiographic changes of renal osteodystrophy could already be identified in the 1st year of dialysis, periarticular bone cysts occurred at the earliest after 2 years, most frequently after 5 years of dialysis. Destructive spondylarthropathy was seen after more than 10 years of dialysis. A positive correlation between these bone lesions and secondary hyperparathyreoidism, dialysis membranes or renal diseases was not found. PMID- 8358214 TI - [Dialysis-associated amyloidosis. Part 1: Biochemistry, clinical aspects, roentgen morphology]. AB - Dialysis-related amyloidosis is characterized clinically by the carpal tunnel syndrome, pain and swelling of joints. These alterations are due to amyloid deposits in the carpal tunnel, in the synovia, ligaments and bones. It has been shown that beta 2m is the major component of this amyloidosis. Serum and urine concentration of beta 2m are markedly elevated in chronic renal failure due to failure of filtration and lack of metabolism by the renal tubular epithelium. beta 2m-derived amyloid is identified by immunohistochemistry using antibodies derived against beta 2m. Radiology shows cyst-like periarticular bone defects, destructive arthropathy and spondylarthropathy. PMID- 8358216 TI - Relief of malignant obstructive jaundice by endoscopic or percutaneous insertion of metal stents. AB - From January 1990 through July 1992 we attempted to treat 42 patients (21 men, 21 women; mean age 69 +/- 2 years) with obstructive jaundice due to inoperable malignant biliary obstructions with insertion of metal stents. 67% of the patients had stenoses of the distal common bile duct, 5% of the proximal common bile duct, and 28% had hilar lesions. Obstructions were due to pancreatic cancer (47%), gallbladder cancer (13%), cholangiocarcinoma (20%), and lymphoma of metastatic cancer (20%). We inserted a total of 51 Wallstents and 17 Strecker Stents with a technical success of 100%. The functional success was 95%. The mean bilirubin level decreased from 18.2 +/- 1.7 mg/dl before to 1.5 +/- 0.2 after stent insertion. In the first 30 days one patient (2%) with hilar malignancy developed an early reobstruction due to tumor bleeding and debris. The 30-day mortality rate was 2%. 2 (5%) patients developed recurrent jaundice within the 3 month follow-up period; 1 had tumor overgrowth of the metal stent, 1 had tumor ingrowth through the mesh. Metal biliary endoprotheses offer sufficient initial relief of malignant obstructive jaundice with reduced morbidity and mortality compared to the placement of conventional plastic stents. However, the long-term results are impaired by stent occlusion due to tumor ingrowth or overgrowth. PMID- 8358217 TI - [Percutaneous intraductal ultrasound of the bile ducts]. AB - Miniaturization of ultrasound probes (6 F, 20 MHz) enables to perform intraluminal sonography of the bile duct in patients in whom a percutaneous transhepatic access has been achieved for diagnostic or therapeutic reasons. Initial experiences in 13 patients with malignant bile duct obstruction and in 8 patients with benign bile duct disease are described. Intraluminal ultrasound displays the normal anatomy and pathologic processes of the bile ducts and reveals information on therapeutic procedures within the bile ducts. Malignant tumors and benign strictures can be differentiated in most cases. In malignant disease, this diagnostic method improves the difficult staging of bile duct tumors and gives information on tumor extension, infiltration of adjacent tissues and vessels, and lymph node enlargement. The limited penetration depth of 1.5-2.0 cm creates problems in the staging of tumors particularly at the hepatic hilum. The procedure is simple and devoid of risks, but requires some refinements and improvements to attain a wider use in different clinical problems. PMID- 8358218 TI - Diagnostic imaging of acute rupture of the thoracic aorta by blunt trauma. AB - Ten patients with acute rupture of the thoracic aorta by blunt trauma were studied. In all instances chest radiographs, computed tomography and aortography were performed. A diagnostic algorithm is proposed for subjects with suspected acute rupture of the thoracic aorta. PMID- 8358219 TI - [Value of radiologic procedures in diagnosis of osteoporosis of the axial skeleton]. AB - Lateral radiograms of the lumbar spine are compared with quantitative mineralometry of vertebral spongiosa done by computed tomography. In 82% of cases, conventional x-rays of the spine give hints towards an increased loss of bone mass. More than 50% of patients with osteoporosis verified by histology are primarily detected by quantitative mineralometry. There is no strict correlation between the severity of osteoporotic disease and the level of mineral content of bone. Conventional x-radiographs of the spinal column are indispensable for estimation of the degree of osteoporosis. Mineralometry can monitor the course of the disease - either to recognize the onset of osteoporosis or to control therapeutic effects. Mineralometry is of less value in primary, early detection of osteoporosis. PMID- 8358220 TI - [Symptomless lung sequestration]. AB - Two cases of asymptomatic intralobar pulmonary sequestrations are reported. Chest radiographs showed a solid intrapulmonary mass left posterior at the base. By computed tomography the exact localization and relationship of the sequesters to the surrounding tissue were demonstrated, and a bolus injection of contrast medium revealed the supplying arteries. The arteriography showed a single arterial supply in both cases and their exact course. In the late phase the pulmonary veins were visualized. Finally a suggested diagnostic workup is given. PMID- 8358221 TI - Regulation of biosynthesis of N-glycolylneuraminic acid-containing glycoconjugates: characterization of factors required for NADH-dependent cytidine 5'monophosphate-N-acetylneuraminic acid hydroxylation. AB - The hydroxylation of CMP-NeuAc has been demonstrated to be carried out by several factors including the soluble form of cytochrome b5. In the present study, mouse liver cytosol was subjected to ammonium sulfate fractionation and cellulose phosphate column chromatography for the separation of two other essential fractions participating in the hydroxylation. One of the fractions, which bound to a cellulose phosphate column, was able to reduce the soluble cytochrome b5, using NADH as an electron donor. The other fraction, which flowed through the column, was assumed to contain the terminal enzyme which accepts electrons from cytochrome b5, activates oxygen, and catalyses the hydroxylation of CMP-NeuAc. Assay conditions for the quantitative determination of the terminal enzyme were established, and the activity of the enzyme in several tissues of mouse and rat was measured. The level of the terminal enzyme activity is associated with the expression of N-glycolylneuraminic acid in these tissues, indicating that the expression of the terminal enzyme possibly regulates the overall velocity of CMP NeuAc hydroxylation. PMID- 8358222 TI - Indications for the enzymatic synthesis of 9-O-lactoyl-N-acetylneuraminic acid in equine liver. AB - Fractionation of horse liver homogenate by centrifugation into heavy membranes at 10,000 x g, microsomal fraction at 105,000 x g, and the supernatant revealed sialate 9-O-lactoyltransferase activity only in the latter fraction. For the enzyme assay, the various fractions were incubated with 14C labelled CMP-N acetylneuraminic acid, N-acetylneuramimic acid and glycoconjugate-bound N acetylneuramimic acid. Lactoylation was identified in three different TLC systems after acid hydrolysis and purification of the sialic acids in the incubation mixtures. Enzyme activity was found only in the supernatant fraction. Glycoconjugate-bound N-acetylneuramimic acid was the best substrate tested, although some lactoylation was also found when using CMP-N-acetylneuraminic acid. PMID- 8358223 TI - Synthesis of phosphites and phosphates of neuraminic acid and their glycosyl donor properties--convenient synthesis of GM3. AB - The importance and requirements for catalytic activation of sialyl donors are discussed, leading to the acid sensitive phosphite and phosphate moiety, respectively, as leaving group and nitriles as solvent. Therefore, from readily available N-acetylneuraminic acid, derivative 1 with phosphochloridites 2a-f and Huenigs' base sialyl phosphites 3a-f were prepared and isolated in high yields. Oxidation of 3a,c with tert-butyl-hydroperoxide afforded the corresponding phosphates 4a,c. As expected, phosphites 3 could be activated in acetonitrile by catalytic amounts of TMSOTf; thus, from 3a-e as donors and lactose derivatives 8A,B as acceptors the ganglioside building blocks 9A and 9B, respectively, were obtained in good yields. The best results were obtained with diethyl phosphite derivative 3a as sialyl donor, which exceeded by far the results obtained with the corresponding phosphate derivative 4a. Trisaccharide 9B was transformed into known 9A and into the fully O-acetylated GM3-trisaccharide 10. PMID- 8358224 TI - Chemoenzymatic galactosialylation with integrated cofactor regeneration. AB - As a precursor for the chemical synthesis of sialylated oligosaccharides, the trisaccharide glycoside Neu5Ac alpha (2-8)Gal beta (1-4)GlcNAc beta (1-O)-pent-4 ene was synthesized starting from GlcNAc beta (1-O)-pent-4-ene, UDP-glucose and N acetylneuraminic acid in a one pot reaction employing galactosyltransferase and alpha (2-6)sialyltransferase in a complete cofactor regeneration system. PMID- 8358225 TI - Inhibition of sialidases from viral, bacterial and mammalian sources by analogues of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid modified at the C-4 position. AB - The inhibition of sialidase activity from influenza viruses A and B, parainfluenza 2 virus, Vibrio cholerae, Arthrobacter ureafaciens, Clostridium perfringens, and sheep liver by a range of 2-deoxy-2,3-didehydro-N acetylneuraminic acid analogues modified at the C-4 position has been studied. All substitutions tested resulted in a decrease in the degree of inhibition of the bacterial and mammalian sialidases. For sialidases from influenza viruses A and B, on the other hand, most of the substitutions tested either had no significant effect on binding or, in the case of the basic amino and guanidino substituents, resulted in significantly stronger inhibition. The results for parainfluenza 2 virus sialidase were mostly intermediate, in that inhibition was neither significantly increased nor decreased by most of the modifications. We conclude that only the influenza A and B sialidase active sites possess acid groups correctly positioned to participate in charge-charge interactions in the region of C-4 of bound substrate, and that the C-4 binding pockets of the bacterial and mammalian sialidases examined are considerably smaller than is observed for either the influenza virus or parainfluenza virus sialidases. PMID- 8358226 TI - Differential effect of various inhibitors on four types of rat sialidase. AB - The inhibitory effect of various compounds on the activities of four types of rat sialidase was investigated. 2-Deoxy-2,3-dehydro-N-acetylneuraminic acid and N acetylneuraminic acid were competitive inhibitors for the sialidases. The former was effective against cytosolic sialidase and intralysosomal sialidase more than two membrane-associated sialidases I and II, the latter being a much weaker inhibitor. A heavy metal ion such as Cu2+ (1 mM) and thiol-modifying 4 hydroxymercuribenzoate (50 microM) caused complete inhibition of the activities of cytosolic sialidase and membrane sialidase I, while no decrease in the activities of intralysosomal sialidase and membrane sialidase II was observed. When 4-nitrophenyloxamic acid and siastatin B, inhibitors of bacterial sialidases, and synthetic thioglycoside GM3 analogue Neu5Ac alpha-s-(2-6)Gal beta(1-4)Glc beta(1-1) ceramide, an inhibitor of influenza virus sialidase, were tested, they did not affect any activity of the rat sialidases. By the differential effect of these inhibitors, the four types of rat sialidase could be discriminated from one another and furthermore from viral and bacterial sialidases. PMID- 8358227 TI - Isolation and properties of the natural and the recombinant sialidase from Clostridium septicum NC 0054714. AB - The natural sialidase of Clostridium septicum was purified and characterized in parallel with the recombinant enzyme expressed by Escherichia coli. The two enzymes exhibit almost identical properties. The maximum hydrolytic activity was measured at 37 degrees C in 60 mM sodium acetate buffer, pH 5.3. Glycoproteins like fetuin and saponified bovine submandibular gland mucin, most of them having alpha(2-6) linked sialic acids, are preferred substrates, while sialic acids from gangliosides, sialyllactoses, or the alpha(2-8) linked sialic acid polymer (colominic acid) are hydrolysed at lower rates. alpha(2-3) Linkages are more rapidly hydrolysed than alpha(2-6) bonds of sialyllactoses. The cleavage rate is markedly reduced by O-acetylation of the sialic acid moiety. These properties are similar to those of other secreted clostridial sialidases. The enzyme exists in mono-, di- and trimeric forms, the monomer exhibiting a molecular mass of 125 kDa, which is close to the protein mass of 111 kDa deduced from the nucleotide sequence of the cloned gene. PMID- 8358228 TI - Identification of a developmentally regulated sialidase in Eimeria tenella that is immunologically related to the Trypanosoma cruzi enzyme. AB - Sporozoites and merozoites of three species of Eimeria, E. tenella, E. maxima, and E. necatrix, that cause diarrhea in chickens worldwide, were examined for their expression of sialidase (SA) activity. The enzyme was found in three species, and the activity of merozoites was 10-20 times higher than that of sporozoites. The enzyme was resistant to degradation by proteases that are normally present in the intestine, a site inhabited by the Eimeria parasites, and it was relatively resistant to heat, with optimum activity being at 40 degrees C, which is within the range of temperature in the chicken intestine (40-43 degrees C). E. tenella SA was immunoprecipitated by monoclonal and polyclonal antibodies raised against the Trypanosoma cruzi SA (TCSA), and enzyme activity was neutralized by these antibodies. E. tenella SA was identified by immunoblots as a doublet of molecular weight 190,000 and 180,000 using, as a probe, anti-TCSA antibodies and antibodies against a synthetic peptide (TR) derived from the long tandem repeat domain of TCSA. Binding of the monoclonal and polyclonal antibodies to E. tenella was completely blocked by TR, but not by an irrelevant peptide (BR). Therefore, E. tenella expresses a developmentally regulated SA that is structurally related to the T. cruzi counterpart. Because of the high SA activity in merozoites, and by analogy with other SA-producing microbes that inhabit mucin rich epithelia, we suggest that the Eimeria SA plays a role in desialylating intestinal mucins to reduce viscosity of the local environment and thereby facilitate parasite migration. The enzyme could also play a role in host cell parasite interaction. PMID- 8358230 TI - Action of rat liver Gal beta 1-4GlcNAc alpha(2-6)-sialyltransferase on Man beta 1 4GlcNAc beta-OMe, GalNAc beta 1-4GlcNAc beta-OMe, Glc beta 1-4GlcNAc beta-OMe and GlcNAc beta 1-4GlcNAc beta-OMe as synthetic substrates. AB - Incubation of synthetic Man beta 1-4GlcNAc beta-OMe, GalNAc beta 1-4GlcNAc beta OMe, Glc beta 1-4GlcNAc beta-OMe, and GlcNAc beta 1-4GlcNAc beta-OMe with CMP Neu5Ac and rat liver Gal beta 1-4GlcNAc alpha(2-6)-sialyltransferase resulted in the formation of Neu5Ac alpha 2-6Man beta 1-4GlcNAc beta-OMe, Neu5Ac alpha 2 6GalNAc beta 1-4GlcNAc beta-OMe, Neu5Ac alpha 2-6Glc beta 1-4GlcNAc beta-OMe and Neu5Ac alpha 2-6GlcNAc beta 1-4GlcNAc beta-OMe, respectively. Under conditions which led to quantitative conversion of Gal beta 1-4GlcNAc beta-OEt into Neu5Ac alpha 2-6Gal beta 1-4GlcNAc beta-OEt, the aforementioned products were obtained in yields of 4%, 48%, 16% and 8%, respectively. HPLC on Partisil 10 SAX was used to isolate the various sialyltrisaccharides, and identification was carried out using 1- and 2-dimensional 500-MHz 1H-NMR spectroscopy. PMID- 8358229 TI - The roles of enteric bacterial sialidase, sialate O-acetyl esterase and glycosulfatase in the degradation of human colonic mucin. AB - Sialidase activity in normal faecal extracts showed a preference for mucin related glycoprotein and oligosaccharide substrates, but the presence of two or more O-acetyl esters at positions C7-C9 on the sialic acids retarded the rate of hydrolysis. A specific sialate O-acetyl esterase was detected with a lower total activity relative to sialidase with mucin substrates and having a pH optimum of 7.8 and a KM of approximately 1 mM sialate O-acetyl ester. A specific glycosulfatase activity was found in faecal extracts using the substrate lactit [3H]ol 6-O-sulfate with a pH optimum of pH 5.0 and a KM of approximately 1 mM. Faecal extracts from ulcerative colitis (UC) patients had higher sialate O-acetyl esterase and glycosulfatase activity, while mucin sialidase activity was unchanged. Metabolically labelled mucin isolated from UC patients contained less sulfate and had lower sialic acid O-acetylation compared with normal mucin. Colonic mucin was degraded more efficiently by faecal extracts from UC patients compared with normal extracts. The UC mucin was degraded more rapidly than the normal mucin by faecal enzyme extracts from both normal and UC subjects. PMID- 8358232 TI - The three-dimensional structure of acyl-coenzyme A binding protein from bovine liver: structural refinement using heteronuclear multidimensional NMR spectroscopy. AB - The 3D structure of bovine recombinant acyl-coenzyme A binding protein has been determined using multidimensional heteronuclear magnetic resonance spectroscopy in a study that combines investigations of 15N-labeled and unlabeled protein. The present structure determination is a refinement of the structure previously determined (Andersen, K.V. and Poulsen, F.M. (1992) J. Mol. Biol., 226, 1131 1141). It is based on 1096 distance restraints and 124 dihedral angle restraints of which 69 are for phi-angles and 8 for chiral centers and 47 for prochiral centers. The new experimental input for the structure determination has provided an increase of 263 distance restraints, 5 phi-angle restraints, and 32 chi-angle restraints in 2 chiral centers, and 31 prochiral centers restraining an additional 23 chi 1, 8 chi 2, and 1 chi 3 angles. The increase of 300 distance and dihedral angle restraints representing an additional 30% of input parameters for the structure determination has been shown to be in agreement with the first structure. A set of 29 structures has been calculated and each of the structures has been compared to a mean structure to give an atomic root mean square deviation of 0.44 +/- 0.12 A (1 A is 0.1 nm) for the backbone atoms C, C alpha, and N in the four alpha-helices A1, residues 4-15, A2, residues 21-36, A3, residues 51-62 and A4, residues 65-84. The loop-region of residues Gly45-Lys50 could not be defined by the restraints obtained by NMR. The program PRONTO has been used for the spectrum analysis, assignment of the individual nuclear Overhauser effects, the integration of the cross peaks, and the measurement of the coupling constants. The programs DIANA, X-PLOR and INSIGHT have been used in the structure calculations and evaluations. PMID- 8358231 TI - Sialyltransferase activity in FR3T3 cells transformed with ras oncogene: decreased CMP-Neu5Ac:Gal beta 1-3GalNAc alpha-2,3-sialyltransferase. AB - We have investigated the activity of CMP-Neu5Ac:Gal beta 1-3GalNAc alpha-2,3 sialyltransferase (EC 2.4.99.4) in FR3T3 cells transformed by the Ha-ras oncogene in which we have previously demonstrated the higher expression of the beta galactosidase alpha-2,6-sialyltransferase (EC 2.4.99.1) [21]. We demonstrate that the presence of the activated ras gene decreases the activity of this specific alpha-2,3-sialyltransferase fourfold. According to the kinetic parameters and to mixing experiments, we can assume that this decreased enzymatic activity reflects a decrease in the number of active O-glycan alpha-2,3-sialyltransferase polypeptides in ras-transformed cells. However, no change in the binding of Peanut agglutinin was observed on the cell surface of ras-transformed FR3T3 suggesting that no change in the sialylation of O-glycan core 1 appeared in these cells, although the activity of the alpha-2,3-sialyltransferase was decreased. PMID- 8358233 TI - Measurement of two- and three-bond 13C-1H J couplings to the C delta carbons of leucine residues in staphylococcal nuclease. AB - A new 1H-detected 3D NMR experiment is described that permits quantitative measurement of two- and three-bond 13C-1H couplings in proteins with selectively 13C-enriched methyl sites. The method is demonstrated for staphylococcal nuclease selectively [5,5 13C]-labeled in all 11 leucine positions and ligated with thymidine 3',5'-biphosphate and Ca2+. Two- and three-bond 13C methyl-proton couplings are reported and, together with the measured three-bond JC alpha C delta in uniformly 13C-enriched staphylococcal nuclease, the chi 2-angles and the stereospecific assignments of the C delta methyl group with respect to the prochiral beta-protons were determined. The same residues that were previously found to have high degrees of internal mobility on the basis of 13C relaxation times have measured coupling constants that are indicative of motional averaging. PMID- 8358234 TI - [2-3H]ATP synthesis and 3H NMR spectroscopy of enzyme-nucleotide complexes: ADP and ADP.Vi bound to myosin subfragment 1. AB - The synthesis of [2-3H]ATP with specific activity high enough to use for 3H NMR spectroscopy at micromolar concentrations was accomplished by tritiodehalogenation of 2-Br-ATP. ATP with greater than 80% substitution at the 2 position and negligible tritium levels at other positions had a single 3H NMR peak at 8.20 ppm in 1D spectra obtained at 533 MHz. This result enables the application of tritium NMR spectroscopy to ATP utilizing enzymes. The proteolytic fragment of skeletal muscle myosin, called S1, consists of a heavy chain (95 kDa) and one alkali light chain (16 or 21 kDa) complex that retains myosin ATPase activity. In the presence of Mg2+, S1 converts [2-3H]ATP to [2-3H]ADP and the complex S1.Mg[2-3H]ADP has ADP bound in the active site. At 0 degrees C, 1D 3H NMR spectra of S1.Mg[2-3H]ADP have two broadened peaks shifted 0.55 and 0.90 ppm upfield from the peak due to free [2-3H]ADP. Spectra with good signal-to-noise for 0.10 mM S1.Mg[2-3H]ADP were obtained in 180 min. The magnitude of the chemical shift caused by binding is consistent with the presence of an aromatic side chain being in the active site. Spectra were the same for S1 with either of the alkali light chains present, suggesting that the alkali light chains do not interact differently with the active site. The two broad peaks appear to be due to the two conformations of S1 that have been observed previously by other techniques. Raising the temperature to 20 degrees C causes small changes in the chemical shifts, narrows the peak widths from 150 to 80 Hz, and increases the relative area under the more upfield peak. Addition of orthovanadate (Vi) to produce S1.Mg[2-2H]ADP.Vi shifts both peaks slightly more upfield without changing their widths or relative areas. PMID- 8358235 TI - SESAME: a least-squares approach to the evaluation of protein structures computed from NMR data. AB - A method is proposed for defining a probability distribution on an ensemble of protein conformations from a 2D NOE spectrum, while at the same time back calculating the experimental spectrum from the ensemble. This enables one to assess the relative quality and significance of the conformations, and to test the consistency of the ensemble as a whole with the experimental spectrum. The method eliminates the need to integrate the cross-peak intensities and is surprisingly insensitive to random noise in the spectrum. In this communication, these advantages are demonstrated by applying the method to simulated data, for which the correct result is already known. PMID- 8358236 TI - Deficiency of dystrophin-associated proteins: a common mechanism leading to muscle cell necrosis in severe childhood muscular dystrophies. AB - Dystrophin is a large cytoskeletal protein encoded by the Duchenne muscular dystrophy (DMD) gene. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoproteins, including the novel laminin-binding glycoprotein called dystroglycan, which provides a linkage to the extracellular matrix. In DMD, the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins. In severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype (SCARMD), a specific deficiency of the 50 kDa dystrophin-associated glycoprotein is found. Thus, the disruption/dysfunction of the dystrophin-glycoprotein complex due to the deficiency of one or more of the dystrophin-associated proteins is presumed to cause the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. This may render muscle cells susceptible to necrosis in two forms of severe childhood muscular dystrophy, DMD and SCARMD. PMID- 8358237 TI - Dystrophin-positive myotubes in innervated muscle cultures from Duchenne and Becker muscular dystrophy patients. AB - Nerve-muscle co-cultures from five Duchenne muscular dystrophy (DMD) patients and one Becker (BMD) patient, were studied by immunocytochemistry with antibodies against different portions of dystrophin. Four DMD patients had a deletion in the dystrophin gene. Some dystrophin-positive myotubes were detected in a few samples of all DMD cases. PCR amplification of exon 8 of the dystrophin gene ruled out a contamination from rat spinal cord during innervation. Our results in three DMD cases, may be explained by a clonal selection of dystrophin-positive fibers observed in muscle biopsies, while in the other two cases, a "frame-restoring" mutation might account for the presence of dystrophin-positive myotubes. The possible expression of "dystrophin-related protein" or dystrophin immature isoform was considered. In the BMD case an abnormal truncated dystrophin was found in innervated muscle cultures, as well as in muscle biopsy. PMID- 8358239 TI - Manifesting carriers of Xp21 muscular dystrophy; lack of correlation between dystrophin expression and clinical weakness. AB - Ten females presenting with muscle weakness and a raised serum creatine kinase revealed abnormalities in the expression of dystrophin in their muscle biopsies and were diagnosed as manifesting carriers of Xp21 Duchenne/Becker muscular dystrophy. Seven cases, aged 3-22 yr at the time of biopsy, had a variable proportion of dystrophin-deficient fibres and an abnormal expression on immunoblot. These were confidently diagnosed as manifesting carriers. Results in the remaining three cases, aged 8-10 yr, were less clear-cut. Dystrophin expression on immunoblots was slightly reduced and some unevenness and reduction of immunolabelling was seen on sections, but dystrophin-deficient fibres were not a feature of these cases. The weakness in the ten carriers ranged from minimal to severe and there was no correlation between the degree of weakness and the number of dystrophin-deficient fibres. Two minimally weak girls had a high proportion of dystrophin-deficient fibres. Our results show that analysis of dystrophin expression is useful for the differential diagnosis of carriers of Xp21 dystrophy and autosomal muscular dystrophy, but that dystrophin expression does not correlate directly with the degree of clinical weakness. PMID- 8358238 TI - Accumulating autofluorescent material as a marker for early changes in the spinal cord of the Mnd mouse. AB - The mouse mutant Motor neuron degeneration (Mnd) displays an adult-onset progressive degeneration of upper and lower motor neurons, with mild symptoms recognizable at 6 months, leading to spastic paralysis and premature death at 10 12 months on the C57B1/6 background. Despite this late onset, abnormally accumulating autofluorescent material can be seen in both the spinal cord and other regions as early as the first month. This pigmented material is present in both increasing numbers of cells, and in increasing amounts within individual cells, as the animals age. Motor neurons then go on to degenerate, while most other cell types stabilize. The level of pathological involvement, well before the onset of clear clinical symptoms, suggests that the full degenerative process is an extremely gradual and protracted one with some selectivity for motor neurons. PMID- 8358240 TI - The glycinamide ribonucleotide transformylase (GART) gene is not responsible for familial amyotrophic lateral sclerosis. AB - Though the nature of the underlying metabolic defect which leads to amyotrophic lateral sclerosis (ALS) remains obscure, certain biochemical anomalies have been found, such as, reduced RNA content in ALS motor neurons. Recently, a gene causing the familial form of ALS (FALS) has been assigned to an interval of approximately 10 cM including the locus D21S58 on chromosome 21q22.1. This region includes the GART gene which encodes an enzyme catalyzing three steps in the de novo biosynthesis of purine nucleotides which are precursors for RNA. A defect of this gene might result in reduced RNA production and predispose to premature death of motor neurons. In order to test GART as a candidate we developed two highly informative DNA markers in this region and carried out linkage analyses for FALS. GART is excluded as a candidate for FALS. PMID- 8358241 TI - Molecular biology and pathology of skeletal and cardiac myogenesis. EMBO Workshop, Baia di Conti, Sardinia, 25 September-1 October 1992. PMID- 8358242 TI - Neuromuscular disorders: gene location. PMID- 8358243 TI - Continuing education and degree programs. Factors affecting nurses entry. PMID- 8358244 TI - Career challenges and distance education. PMID- 8358245 TI - Preceptors: a research study. PMID- 8358246 TI - The move to outcomes measurement. PMID- 8358247 TI - Top-level administrators. A study of continuing education needs. PMID- 8358248 TI - Stress decreases the serum level of osteocalcin. AB - During a study undertaken to characterize the time course of the osteocalcin response to bone fractures, lower than normal values of serum osteocalcin (1.7 +/ 0.9 vs. 3.3 +/- 1.3 ng/ml, P < 0.001) were found in the basal samples (blood obtained 48-72 h after fracturing). Suspecting that such a decrease could be due to the stress response induced by the fracture, for corticosteroids are known to diminish serum osteocalcin, we extended our study to another two stressful situations of high stress: acute myocardial infarction and elective abdominal surgery. Indeed, the concentration of osteocalcin was also significantly diminished in both of these (2.0 +/- 0.9 ng/ml, P < 0.0005; 1.5 +/- 1.0 ng/ml, P < 0.0001). To further characterize this phenomenon, the time course of osteocalcin changes during the 24 h following abdominal surgery was studied in a second group of patients. The decrease was found to begin soon after surgery. In order to exclude the immobilization present in those three situations as the cause of the decrease in serum osteocalcin, a group of patients with retinal detachment was studied. Their serum osteocalcin levels were normal. It is concluded that serum osteocalcin levels decrease in stressful situations. Therefore, they should be interpreted cautiously when used as a marker of osteoblastic activity in this setting. PMID- 8358249 TI - Declining bone loss rate variability with increasing follow-up time. AB - Bone loss rates are believed to vary substantially among post-menopausal women. The belief, however, might be largely based upon comparisons of loss rates measured with considerable error. This issue arises because the precision of the bone mass instrumentation (1-2% errors in measuring bone mass) is similar in magnitude to the loss rate (typically 1-2% of bone mass per year). The 'true' variability in loss rates, however, can be estimated by adjusting for instrument errors. An equation is presented which estimates the true variability in loss rates from a study sample. The adjustment was examined using a cohort of post menopausal, Japanese-American women living in Hawaii. The study examined the calcaneus, distal, and proximal radius sites. The results suggest that measurement errors did not markedly inflate the bone loss variability. Even after adjustment for measurement errors considerable variability in loss rates remained. The variability was examined for various follow-up durations. Both the observed and adjusted loss rates had smaller standard deviations over long intervals than over short intervals. This result suggests that the more extreme rates of change in bone mass over a year or two were often not sustained. The implications of this finding for sample size calculations in longitudinal studies are examined. The results also indicate that the length of follow-up and instrument precision should be taken into consideration when comparing the proportion of fast losers between populations. PMID- 8358250 TI - Determinants of lumbar bone mineral density in normal weight, non-smoking women soon after menopause. A study using clinical data and quantitative computed tomography. AB - OBJECTIVES: Is there an influence of oral contraceptive use, parity and lactation on early postmenopausal bone mass? Is assessment of reproductive history, body weight in combination with biochemical markers of bone metabolism suitable to predict lumbar bone mass soon after menopause? STUDY DESIGN: A cross-sectional study in 94 healthy, normal weight, non-smoking women, 1-3 years after spontaneous menopause. Bone mineral density (BMD) of the lumbar spine was measured with single energy quantitative computed tomography. RESULTS: Multiple regression analysis showed that only total duration of lactation and alkaline phosphatase (AP) levels are independently related to trabecular BMD (P = 0.001 and P = 0.002 respectively). AP was also associated with cortical BMD (P = 0.003). Assessment of reproductive history, body mass index and biochemical markers of bone metabolism could only account for 17% of the variation of trabecular BMD observed in the study population. CONCLUSION: This study suggests that total duration of lactation rather than parity is associated with trabecular BMD of the spine. Clinical assessment of risk factors unsuccessfully predicts lumbar BMD in healthy, early postmenopausal women. PMID- 8358251 TI - Cyclic stretch increases alkaline phosphatase activity of osteoblast-like cells: a role for prostaglandin E2. AB - We investigated the effects of applied cyclic stretch on osteoblast-like cells using a computerized, pressure-operated instrument that physically deforms the cells. Cyclic stretch increased DNA and collagenous protein synthesis and enhanced alkaline phosphatase activity in the cells. These effects were considered to be regulated through prostaglandin E2 production since this stretch reduced the levels of prostaglandin E2 in the medium and when prostaglandin E2 was added exogenously, there was a significant decrease in the alkaline phosphatase activity. PMID- 8358252 TI - Effects of 1,25-dihydroxyvitamin D3 and growth hormone therapy on serum osteocalcin levels in children with growth hormone deficiency. AB - In order to investigate the influence on bone metabolism of growth hormone (GH), we evaluated the response to an acute load of 1,25(OH)2D3 (Rocaltrol) (1.5 micrograms/day for 4 days) in 16 growth hormone-deficient prepubertal children (11 boys and 5 girls, aged from 6.2 to 9.6 years) both before and after 1 month of human GH (hGH) therapy (0.1 IU/kg/day, 6 times per week). Before and after the 1,25(OH)2D3 load, serum IGF-I, osteocalcin, Ca, P, alkaline phosphatase (ALP) and urinary excretion of Ca and P were measured. The serum levels of osteocalcin rose significantly after the first 1,25(OH)2D3 load, without an increase in IGF-I values and with a slight non-significant increase in serum Ca and P. Almost superimposable increases of osteocalcin, Ca and P were observed after 1 month of hGH therapy, with a significant increase of IGF-I, but they did not rise further after the second 1,25(OH)2D3 load. On the basis of our results, 1,25(OH)2D3 seems to have a stimulatory action on osteoblastic activity even in the absence of normal levels of GH. However, there is no apparent additional stimulatory activity after administration of hGH. Osteocalcin level behaviour during our study might suggest that GH and 1,25(OH)2D3 have a common and easily saturable stimulatory pathway on osteoblastic function. PMID- 8358253 TI - Physical activity and bone mass: exercises in futility? AB - Growing bone responds to low or moderate exercise through significant additions of new bone in both cortical and trabecular moieties and results in adaptation through periosteal expansion and endocortical contraction. Intracortical activation frequency declines in growing bone in response to exercise, reducing porosity and the remodelling space. These adaptations can be maintained into and throughout adulthood. Young bones have a greater potential for periosteal expansion than aging bone, allowing them to adapt more rapidly and efficiently to an acute need for increased strength, but a threshold level of activity exists above which some bones respond negatively by suppressing normal growth and modelling activity, reducing geometric, mechanical and material properties in cortical and trabecular bone. From cross-sectional studies, differences in bone mass between exercising and non-exercising adults are generally less than 10%, but do not account for exercise history which may be very important, and often fail to consider important confounding variables. There is sufficient longitudinal data to demonstrate that moderate to intensive training can bring about modest increases of about 1-3% in bone mineral content (BMC) of men and premenopausal women. In young adults very strenuous training may increase BMC of the tibia up to 11% and its bone density (BD) by 7%, but may represent periosteal woven bone formation in response to excessive strain. Some evidence shows that exercise can also add bone mass to the post-menopausal skeleton, although the amounts are site-specific and relatively modest. Increases as high as 5-8% can be found after 1-2 years of intensive exercise, but additions of bone to the femur and radius are generally less than 2%, well within the range of the remodelling space and measurement precision. Although increases in bone mass of the post menopausal skeleton may be extremely modest, physical activity is important to preserve bone mass and muscle function. Detraining reduces any bone mass increase to pre-existing values so that long-term benefits are only retained with continuing exercise. Most importantly, the amount of bone gain that can be achieved appears dependent primarily on the initial bone mass suggesting that individuals with extremely low initial bone mass may have more to gain from exercise than those with moderately reduced bone mass. PMID- 8358254 TI - Prevention of alcohol-related accidents in the community. AB - This paper establishes a conceptual and operational basis for development of community prevention programs to reduce alcohol-related accidents. A public health perspective of accidents is proposed as the philosophical basis for local prevention interventions in which accidents are viewed as system problems (system outputs, if you will) not simply problems caused by a few alcohol-dependent individuals. Since there are no examples of controlled community prevention research projects (trials) which have demonstrated a reduction in community-level alcohol-related accidents, such controlled trials are needed in the future. An example of one being developed by the Prevention Research Center, Berkeley, CA is provided. Without such controlled trials, prevention research will be unable to demonstrate that such accidents can actually be reduced. This paper explores the applications of a public health perspective to the prevention of alcohol-involved accidents at the community level including a conceptual model of alcohol-involved trauma and suggested design, alternative local interventions, possible outcome measures, and phases for community prevention of alcohol-related accidents. PMID- 8358255 TI - The Stockholm County programmes for accident and alcohol prevention and injury surveillance--initial experiences. AB - A comprehensive programme for accident prevention and injury surveillance was established in Stockholm County in 1988. Its main objective is to reduce the morbidity and mortality of unintentional injuries by 25% by the year 2000, and by more than 25% in the high-incidence groups. An accident prevention unit has been assigned to task of planning and implementing an accident prevention programme, while a programme for prevention of alcohol-related problems was set up later. An injury epidemiological unit at the Karolinska Hospital is responsible for coordinating injury surveillance, which is an important contribution for monitoring and evaluation of the prevention programmes. On injured patients information about type of injury, extent of injury, place, activity, injury mechanism, external cause of injury, treatment and other items is entered on a special registration form. In (10%) of 11,327 injury events alcohol was considered by the physician to be a main or contributory cause of the injury, with a predominance among males. An act of violence was approximately three times as common among males and five times as common among females with alcohol involvement than among cases without alcohol involvement. The injury surveillance can be an important means for evaluation of programmes for prevention of injuries and alcohol-related events. PMID- 8358256 TI - Special issue: Alcohol-related accidents and injuries. PMID- 8358257 TI - Research on and prevention of alcohol-related trauma: phases, patterns, and issues. PMID- 8358258 TI - Societal norms and risk-taking behaviour: inter-cultural comparisons of casualties and alcohol consumption. AB - Inter-cultural comparisons point to associations among aggregate rates of consumption and certain alcohol-related complications, particularly chronic effects, such as liver cirrhosis mortality. Accidental, poisoning and violent incidents are not considered to have as strong an association with societal drinking patterns, since situational, environmental and interactional features contributing to the incident are likely to play a strong role relative to the volume of alcohol consumed. This paper compares annual alcohol consumption rates and male and female mortality rates for liver cirrhosis and 12 main accidental/violent causes of death for Canada, Finland, France, the Netherlands, Switzerland, and the US between 1965 and 1987. Using filtering techniques to account for autocorrelation, conservative measures of association were developed. The results indicate that while statistically significant correlations were evident with regard to liver cirrhosis and suicide in some jurisdictions, in most instances the comparisons were not significant. Further work is suggested with regard to the following: utilizing more refined approaches to examine the covariations of casualties and alcohol consumption, and studies combining aggregate level investigations with those focusing at the group or interactional level--in particular those specifying and examining societal norms and risk taking at the group and sub-population levels. PMID- 8358259 TI - Alcohol and non-traffic unintended injuries. AB - In a review of the English language literature on alcohol and unintentional injury we identified 21 studies on falls, 36 on drownings and 32 on burns from 1947-1986. The proportion of fatal and non-fatal fall victims who had been drinking ranged from 21-77%, and 18-53% respectively. In three more recent studies, 35-63% of persons fatally injured in falls had been drinking. In five other studies 13-37% of persons injured in non fatal falls had been drinking. In our earlier review of drowning studies with complete ascertainment and duration of submergence specified, 27-47% of those who drowned had positive BAC's. In eight subsequent studies, alcohol was identified in 21-47% of drowning deaths. In our earlier review alcohol was involved in 9-86% of burn deaths. In five more recent US studies, alcohol was found in 12-61% of fatally injured burn victims. Case control studies are needed to establish whether alcohol increases the risk of trauma. Studies are also needed of interventions to reduce the proportion of these injuries where alcohol is involved. PMID- 8358260 TI - Methodological approaches and problems in research into alcohol-related accidents and injuries. AB - A classification system for methodologies and problems in research on alcohol related accidents and injuries is introduced. On the basis of this system, possible designs and statistical methods are presented, and their possible contributions to research on alcohol-related accidents/injuries are evaluated. Special consideration is given to potential biases in secondary data sources, and to methods of overcoming these biases. Finally, the need for more theory-driven research is established. PMID- 8358261 TI - Causal attributions in the explanation of alcohol-related accidents. AB - This paper discusses issues related to the cognitive and communicational activity of ascribing a causal role to alcohol use in accidents. It is argued that in addition to the empirical relationships to be explained causal attribution is limited by two other types of empirical contingencies: the cognitive processing of information available for causal attribution, and the representation of this information in language (encoding and decoding as part of communication). Only the latter two types of restrictions in causal attribution are discussed, since its logical requirements are covered by well known methodological principles. On the linguistic and communicative side, limitations and biases in causal ascription are introduced by (1) the three central concepts ('alcohol', 'cause', 'accidents') due to properties inherent in language; (2) the (often implicit) selection of boundary conditions; (3) heuristic inference rules; and (4) the tendency towards thematic closure in describing and explaining phenomena. It is suggested that social, psychological and interactional causal processes have been overlooked in attributing causal links between alcohol use, hazardous behaviour and accidents. PMID- 8358262 TI - The measurement of alcohol-related accidents. AB - This paper examines some of the major ethical and research issues associated with the measurement and recording of alcohol-related problems. Because self-reports of the history of the amount of alcohol ingested are sometimes unreliable, the assessment of the role of alcohol in casualties often relies on a variety of methods which are both diverse and interrelated. The unique measurement problems posed by the diversity of alcohol measures are reviewed and issues in selection and recording bias of alcohol's involvement in injury are discussed. A number of fundamental ethical and moral issues related to measurement are identified. PMID- 8358263 TI - Personal willingness to pay for prevention: evaluating the consequences of accidents as a basis for preventive measures. AB - This paper argues that if scarce resources are to be allocated efficiently and to greatest advantage then it is necessary to have explicit monetary measures of the benefits of reduced accident rates so that these benefits can be weighed against costs in the process of determining the appropriate amount to expend on alcohol related accident prevention programmes. The conceptual issues related to the definition and estimation of monetary values of safety are discussed and the case in favour of basing such values on individual willingness to pay for safety is developed. The paper then summarises existing empirical estimates of willingness to-pay based values for the prevention of fatalities and reports the preliminary results of recent work aimed at estimating willingness-to-pay based values for the prevention of non-fatal injuries. The paper concludes by examining the applicability of existing empirical estimates of the value of safety in the alcohol-related accident context and the transferability of estimates derived in developed countries to the developing country context. PMID- 8358264 TI - Alcohol and injuries: a review of international emergency room studies. AB - This paper reviews emergency room (ER) studies from a number of countries which have focused on the association of alcohol and casualties. The review emphasizes studies which used probability sample of patients to represent the population of the emergency facility where the data were collected, and which separated injured patients from patients with medical conditions not due to injuries (the 'non injured'). Reviewed here are studies concerned with: (1) estimated prevalence of positive blood alcohol at the time of the ER visit; (2) self-reported alcohol consumption prior to the event resulting in a need for ER treatment; (3) patients' descriptions of their usual drinking patterns and alcohol-related problems; (4) predictions of casualties and of alcohol-related casualties. Comparisons of findings from several countries are also presented. Comments on limitations of ER studies as well as other issues pertaining to the usefulness and interpretation of such data, and future directions for research in emergency room populations are discussed. PMID- 8358265 TI - Alcohol in home and leisure injuries. AB - The part that alcohol plays in non-motor vehicle unintentional injuries is not well known. Injuries at home and during leisure form a very heterogeneous group. Alcohol involvement varies considerably from one subgroup to another: for example, all cases of alcohol poisoning involve alcohol by definition, whereas alcohol involvement is very infrequent in sports injuries. One-third of falls, half of drownings and fire deaths and two-thirds of hypothermia deaths involve alcohol. Young and middle-aged males form a risk group of alcohol-related trauma. Alcohol involvement varies also from country to country: deaths from alcohol poisoning are several times as common in Finland as in other Western countries. In contrast to experience in Western countries, in Dar es Salaam, Tanzania, wealthier injured Africans were found to have alcohol involvement more often than poor Africans. Alcohols seems to increase the risk of falling, bicycle and motor vehicle injuries largely to the same extent. The relative importance of the two main components of alcohol-related risk--risk-taking and impaired psychomotor functions--requires further exploration in each main external cause category of home and leisure injuries. PMID- 8358266 TI - The occurrence and epidemiologic features of alcohol-related occupational injuries. AB - This paper presents a review of published literature on alcohol-related occupational injuries. Based on the information presented the true magnitude of the problem of alcohol- and work-related injuries has not been accurately assessed and the epidemiologic features of this problem have not been properly evaluated. There is some evidence, albeit incomplete, that alcohol contributes to work-related injuries, but the extent is not known. Further, the risk of injury by specific industry and occupation has not yet been elucidated. Analytic studies which include control groups and which assess confounding variables are needed so as to aid in the design of effective countermeasure strategies. Even when alcohol is detected, its role in the causal pathway from the worker-energy interaction to injury onset (or exacerbation) has not been studied. PMID- 8358267 TI - Alcohol and civil aviation. AB - In aviation medicine until the early 1960s the idea that pilots would fly while under the influence of alcohol was taboo. In the United States of America, the taboo was broken when it became known that 30% of fatally injured pilots in general aviation had been under the influence of alcohol. Since then the rate has declined to 10%. No fatal accidents involving alcohol have been recorded in airline passenger transport. The prevalence of pilots flying under the influence of alcohol is unknown. The lowest studied blood alcohol concentration (BAC) with impaired flying skill today is 0.025%, effectively suggesting that the permitted level should be zero, but many aviation authorities have not yet translated such findings into rules and regulations. In the early 1970s the US Federal Air Surgeon began to re-issue licences for rehabilitated alcoholic pilots. Previously alcoholism had been a reason for mandatory permanent grounding. The possibility of returning to the cockpit first opened the way to early recognition of alcoholic pilots on a larger scale. Today many airlines have their own alcohol programmes. This paper gives a brief account of the Swissair programme with its four phases: observation, intervention, treatment and follow-up. PMID- 8358268 TI - Issues in cross-national comparisons of crash data. AB - While national accident record systems appear to provide an attractive method of comparing the effectiveness of traffic safety programs, differences in definitions, data collection methods and file structure may lead to misleading conclusions. Variations in crash definitions and methods for measuring alcohol involvement are described and illustrated with data from US crash files. Examples of international comparisons are provided. PMID- 8358269 TI - Alcohol and accidents in Switzerland--a critical review. AB - The analysis of alcohol-related traffic accidents points to a negative relationship between the average amount of alcohol consumed and the percentage of alcohol-related accidents. The data show that the officially registered problem rates among drivers under the influence of alcohol depend primarily neither on consumption trends nor on general preventive factors, but, rather on the capacity for accident detection, the recording practices of the authorities and a less tolerant public opinion. Regional differences in the willingness to enforce control measures are related to varying cultural drinking contexts. The under reporting of occupational accidents reflects an undue emphasis in insurance statistics which are based on a guilt/moral concept which is used to justify sanctions, such as cuts in insurance benefits. It is clear from the empirical evidence, that the broad press coverage on 'alcohol-related' ski accidents proves to be a typical case of problem amplification. PMID- 8358270 TI - Effects of mass media communications on health and safety habits: an overview of issues and evidence. AB - A review is presented of factors that have been investigated on their relevance in mass media communications that are specifically designed to alter health and safety related behaviours of the recipients. While alcohol consumption is a major concern in this paper, the evidence regarding the effective use of mass communications for the modification of other health and safety habits has also been incorporated. Specific topics include the choice of yardstick of effect, study methodology and the strength of conclusion this permits, as well as the dependency of the effect of mass communication upon its four constituent components: the source, the content of the message, the channel of communication, and the characteristics of the recipients. Reference is made to the effect of educational journalism related to the prevention of health problems and to efforts to increase the educational value of traffic accident reports in daily newspapers through the inclusion of information that is potentially helpful to accident avoidance. PMID- 8358271 TI - Punishment as a factor in preventing alcohol-related accidents. AB - As a humanitarian and economic 'bad', infliction of punishment requires justification in terms of compensating achievements, as well as moral appropriateness. In the context of road accidents, there is evidence that increasing the certainty and swiftness of threatened punishment may deter risky behavior, although increasing the severity of the threat seems ineffective. These effects may be generalizable to other kinds of accidents, but empirical evidence is lacking. A further possibility for the justifiable use of punishment is in its application to negligent service of alcohol. PMID- 8358272 TI - [The constant electrical potentials of the skin as an integral index of the functional state]. AB - The electric potential difference between the head and hind limb of monkeys was studied before, during and after 2h-restraint in a supine position. The kinetics of electric potentials depended on the initial electric polarity of animals. The role and place of the basal system of epithelium (basal membrane and basal cell layer) in functioning of multicellular organisms is discussed. PMID- 8358273 TI - [The effects of the white gene on coat pigmentation in mouse aggregation chimeras]. AB - We obtained eight Mi(wh)/+<==>Mi(wh)/Mi(wh) chimeras using embryos of two mutant substrains of Mi(wh)/Mi(wh) mice with different isozymes Gpi-1(aa) and Gpi-1(bb). Chimerism was determined by the mosaicism of retinal pigment epithelium and electrophoretically different variants of glucose phosphate isomerase. The patterns of coat pigmentation in all chimeras were similar to those in Mi(wh)/+ heterozygotes. Despite the high proportion of the parental Mi(wh)/Mi(wh) component in three chimeras, the phenotype of their coat pigmentation was also similar with that of Mi(wh)/+ mice. The chimeras lacked mosaic-pigmented hairs. These data suggest presence only one cell population of Mi(wh)/+ melanoblasts that actively proliferate and colonize almost all forming hair follicles. Hence, the proliferation and/or differentiation of Mi(wh)/+ melanoblasts is not suppressed in the Mi(wh)/Mi(wh) dermis and epidermis. The Mi(wh) gene acting in melanoblasts leads to the block of their proliferation at the early stages of development in the homozygotes. PMID- 8358274 TI - [The role of glutathione in shaping the metabolic response of the cell to hypoxia]. AB - The role of glutathione in metabolic response of the cell to hypoxia is discussed. Experiments were carried on random bred white female rats and their offspring. The antihypoxic effect of glutathione was studied using a low-pressure chamber model of acute hypoxic hypoxia and a perfused heart. When administered during the last third of pregnancy, glutathione stimulates in the female and in the foetus development of protective-adaptive reactions, thus increasing the resistance of hypoxia. This is expressed in an increased resistance to acute hypoxia and an improved mechano-energetic coupling of the myocardium. A proposed mechanism underlying the hypoxic, energizing effect of glutathione is related to decreased hyper-reduction of the NAD-dependent region of the respiratory chain and the recovery of its ability to synthesize ATP in the first site of oxidative phosphorylation. The results obtained allow us to outline perspectives of search for new compounds controlling the level of glutathione in the cells and, hence, activating the development of adaptational compensatory mechanisms for protection against de-energizing effect of hypoxia and similar factors. PMID- 8358275 TI - [The prospects for using marine algae]. AB - Different aspects of utilization of the products of marine algae processing are discussed: phycocolloids, sterins, isoprenoids, etc. The natural resources of algae are decreased due to their intensive exploitation. Hence, the development of algal mariculture becomes very urgent. PMID- 8358276 TI - [The prediction of the superactivity of embryo-toxic benzine and indole derivatives by the discriminant analysis method]. AB - The discriminant functions allowing to predict the phenomenon of superactivity for some embryotoxic neurochemicals by means of tabular electronic and lipophilic parameters are received. The prognosis possibility of the received functions for benzene and indole derivatives on the sea urchin embryos is about 93%. PMID- 8358277 TI - [A comparative study of the action on the hemostatic system of extracts from the flowers and seeds of the meadowsweet (Filipendula ulmaria (L.) Maxim.)]. AB - Flowers and seeds of Filipendula ulmaria show a high level of anticoagulant activity. Their anticoagulant and fibrinolytic effects were demonstrated after per os administration of the extracts. The seed extracts exert equally high anticoagulating effects when administered in vivo and in vitro. PMID- 8358278 TI - [The inhibition of bile acid synthesis in cultured rabbit hepatocytes by bezafibrate]. AB - Primary culture of rabbit hepatocytes was used for study the influence of hypolipidemic drug bezafibrate on bile acid production. Bezafibrate inhibits bile acid synthesis from endogenous and exogenous (lipoprotein) cholesterol at concentration range 1-10 micrograms/ml. Such inhibitory action of bezafibrate on bile acid synthesis should be kept in mind while applying hypolipidemic treatment. PMID- 8358279 TI - Food additives and contaminants and their contribution to the human cancer load. PMID- 8358280 TI - The epidemiological evidence concerning intake of mutagenic activity from the fried surface and the risk of cancer cannot justify preventive measures. AB - In the fried meat surface layer (the meat crust) mutagenic heterocyclic amines are formed during cooking. A human cancer risk is conceivable after intake of such mutagenic activity. We investigated the current literature mentioning fried foods, and six studies of colorectal cancer, three of stomach cancer and one each of cancer of the breast, lower urinary tract and pancreas are included. None of the reports tried to assess directly the intake of mutagenic activity from the fried surface. One indirect measure of mutagenic activity is to look at the browning of the meat surface; two investigations are available for this variable. The content of mutagenic activity in the surface may vary with the 'doneness' of meat and two studies consider this variable. Another indirect measure is to compare results from meat irrespective of cooking methods (ie, comparing meat not fried with fried meat or fried foods). There are several validity problems in the reviewed studies. Major potential sources of bias include, quite apart from misclassification of mutagenic activity, possible confounding factors from meat per se and fat. The epidemiological evidence in the field is sparse and cannot justify preventive measures. PMID- 8358281 TI - Self-administered faecal occult blood tests do not increase compliance with screening for colorectal cancer: results of a randomized controlled trial. AB - In the UK, compliance with conventional faecal occult blood (FOB) tests such as Haemoccult is about 50% in the general population. It has been postulated that characteristics of the performance of conventional tests, in particular the need for dextrous gathering and manipulation of faeces, delay in receiving results, and the recommended dietary restrictions, may all diminish compliance. New FOB tests have been developed, popularly termed 'magic toilet paper' tests, which not only minimize faecal manipulation but are also self-reported. Compliance rates with two self-administered faecal occult blood tests (Early Detector and Coloscreen Self-Test) were compared with Haemoccult in a randomized trial involving 1,842 subjects aged 40-74 years. Use of self-administered FOB tests did not increase compliance significantly, with rates of 52.1% for Early Detector, 50.6% for Coloscreen and 49.1% for Haemoccult. Moreover, dietary restriction did not reduce compliance significantly (restricted 49.3%, unrestricted 51.8%). A wide variation (from 1.3% to 21.4%) in positivity rates was observed which was dependent on which of the three tests was used and whether dietary restrictions were applied. Since the physical aspects of test performance do not appear to determine an individual's decision to be screened, self-administered tests will not overcome the problem of poor compliance with FOB screening. PMID- 8358282 TI - Patterns of Pap smear use in the Rimini area: an analysis of women's attitudes to the test. AB - The use of the Pap test is a method of the prevention of cervical cancer in our local division of the Sanitary Unit and has been studied with the help of a questionnaire which was completed by women who had adopted this test. The socioeconomic characteristics, level of education, occupation and general attitudes regarding the Pap test as well as how the women had acquired knowledge of the test, have all been examined. From an analysis of the answers, we have been able to trace a precise social, economic and cultural profile of the type of women who take advantage of this test. Principally, we are dealing with women aged 40-49 years, often with children, with a medium to low level of education, who are mainly housewives and white-collar workers. Very few elderly women present themselves for the Pap test. We have noticed that there is a direct decrease in the use of preventive methods, proportional to the increase in age. These results demonstrate that an erratic use of this preventive method, in the absence of an organized screening programme, seems only to involve women who are among those at less risk from cervical cancer. PMID- 8358283 TI - Cancer patterns in three African populations compared with the United States black population. AB - Cancer incidence rates and patterns in three African populations in the Gambia, Mali and South Africa, have been compared with corresponding data on the Black population in Connecticut, USA. In the African populations, total rates for cancer are much lower than that of US Blacks, even allowing for under-reporting. Chief cancers are those of the oesophagus, liver and cervix. In Mali, stomach cancer is very common. As to trends, among South African Blacks, a population in transition, rates are rising, albeit slowly, of cancers of prosperity--prostate, lung, breast and colon-rectum. Salient questions are: can the number of cancers of underprivilege be lessened, and can cancers linked with rising socioeconomic states be restrained? Discussions of common risk factors, including diet, reproduction, smoking and drinking practices, indicate that for Africans as a whole, continuing poverty will prevent major changes in cancer pattern and rises in occurrence of the disease. However, should prosperity increase for Africans in big cities, rates are ultimately likely to attain those prevailing in the US Black population. Significant avoiding action seems almost impossible. PMID- 8358284 TI - Prevalence of Helicobacter pylori infection in patients with precancerous changes and gastric cancer. AB - Several papers suggested a role for H. pylori infection in gastric cancer. We evaluated the prevalence of H. pylori infection in an endoscopic population of patients with gastric precancerous conditions and lesions by studying biopsies from 252 patients and recording the presence and degree of H. pylori infection. Patients were subgrouped as follows: chronic non-atrophic gastritis (CG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), epithelial dysplasia (ED) and gastric cancer (K). As control populations, patients with duodenal ulcer (DU) and patients with no endoscopic and histologic damage (CO) were investigated. H. pylori infection rate increased with age, but became significantly lower (P < 0.001) with the progression of gastric mucosal damage: DU 85%, CG 72%, CAG 58%, particularly in the antral type (39%), IM 63% overall, ED 44% and K 35%. The density of colonization showed the same trend (P < 0.001). Of the K patients, only 36% were H. pylori positive in the adjacent mucosa. Anti-H. pylori antibodies (IgG, IgA and IgM) were also tested. A concordance in the diagnosis between histology and serology was obtained in 82% of the cases. In our experience, H. pylori infection correlates inversely with the presence of gastric precancerous changes and cancer. A cautious interpretation of the epidemiological data regarding H. pylori infection and gastric cancer is therefore, in our opinion, mandatory. PMID- 8358285 TI - Effects of fruit juices, processed vegetable juice, orange peel and green tea on endogenous formation of N-nitrosoproline in subjects from a high-risk area for gastric cancer in Moping County, China. AB - The effects of four fruit juices, processed vegetable juice, orange peel, green tea and low dose vitamin C on endogenous N-nitrosation in 86 subjects from a high risk area for gastric cancer in Moping County, China were studied using urinary excretion of N-nitrosoproline (NPRO) as an indicator. After ingestion of 300 mg L proline, urinary excretion of NPRO was significantly increased from a baseline of 2.5 +/- 1.6 micrograms/day to 8.7 +/- 6.2 micrograms/day. (P < 0.001). Vitamin C (75 mg) administration significantly reduced NPRO formation (62.3%, P < 0.002) although NPRO excretion remained higher than the baseline level (4.2 +/- 1.3 vs 2.2 +/- 1.2 micrograms/day, P < 0.001). Intake of fruit juices and green tea extracts (containing 75 mg vitamin C) or of orange peel powder (containing 3 mg vitamin C) together with 300 mg L-proline inhibited NPRO formation effectively to the baseline level or to levels significantly lower than the baseline level (P < 0.05-0.005). A processed juice of a number of vegetables (300 ml) significantly catalysed endogenous nitrosation (14.7 +/- 11.8 vs 9.4 +/- 4.7 micrograms/day, P < 0.05). Endogenous N-nitrosation was unaffected by the presence of intragastric lesions. The present study shows that endogenous nitrosation in this population is profoundly affected by environmental factors and that inhibitors, such as vitamin C, alpha-tocopherol and other non-nutritive compounds in the foods do inhibit endogenous nitrosation either synergistically or in an additive manner. The significance of fruits and vegetables in prevention of human cancers is discussed. PMID- 8358286 TI - Regional and national variation in lung cancer mortality in Italy and Czechoslovakia. AB - In developed countries lung cancer mortality has been shown to be related to lifestyle, occupational and environmental aspects, diet, and other factors which may vary widely from one region to another. To investigate inter-area differences in lung cancer mortality and cigarette smoking a descriptive study has been carried out in three areas of Italy and two republics of Czechoslovakia. The highest death rates from lung cancer were found in the Czech Republic and Northern Italy, for both sexes. Analysis of age-specific rates by birth cohort, comparing all five areas, showed the greatest differences in trends between Slovakia and Northern Italy in men, and between the Czech Republic and Southern Italy in women. The lowest rates were observed in Southern Italy throughout the period under study, particularly among women. Making allowance for the latency period between the onset of exposure and the development of the disease, data on the occurrence of lung cancer could be interpreted looking at previous smoking habits. An imperfect overlap between the trend of cigarette smoking and the corresponding lung cancer mortality pattern was present in Northern and Southern Italy, a finding suggesting that even non-smoking-related factors could have played a significant role in lung cancer aetiology. PMID- 8358287 TI - Occupational exposures and thyroid cancer: results of a case-control study. AB - A case-control study on thyroid cancer concerning 180 cases and 360 controls aged 20-70 years at diagnosis was performed. Both females and males were included. Of the cases, 63% had had papillary thyroid cancer. Work with diagnostic X-ray investigations constituted a risk factor for thyroid cancer of the papillary type yielding an odds ratio (OR) of 2.9 with 95% confidence interval (CI) = 1.1-8.3. For women only OR was 3.3 (CI = 1.2-9.8). The results also indicated that work as a lineman, which entails exposure to electromagnetic fields and chemicals, increased the risk. Exposure to impregnating agents gave an increased OR = 2.8 with CI = 1.0-8.6. For men only OR was 3.8 with CI = 1.1-16. Women who were previously smokers and female current smokers had significantly decreased risks with OR = 0.5 (CI = 0.2-0.96) and OR = 0.6 (CI = 0.3-0.96), respectively. PMID- 8358288 TI - Inhibition of dexamethasone-induced cytochrome P450-mediated mutagenicity and metabolism of aflatoxin B1 by Chinese medicinal herbs. AB - Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumours. We previously showed that they inhibited mutagenesis, DNA binding and metabolism of aflatoxin B1 (AFB1) and benzo(a)pyrene (BaP) bioactivated by Aroclor 1254-induced rat S9. The purpose of this study was to investigate the effects of OD and SB on the mutagenicity of AFB1 in Salmonella typhimurium TA100 using dexamethasone (DXM)-induced rat hepatic S9, on cytochrome P450-linked aminopyrine N-demethylase (APND) activity in DXM-induced hepatic microsomes and on the metabolism of AFB1 by DXM-induced S9 using high-performance liquid chromatography (HPLC). The experimental results showed that OD and SB consistently inhibited the mutagenicity of AFB1 bioactivated by either non-induced or DXM-induced S9. These effects correlated with the inhibition of cytochrome P450-linked APND activity in DXM-induced microsomes and with an inhibition of DXM-induced S9 mediated metabolism of [3H]AFB1 as determined by HPLC. Since DXM treatment has been associated with an induction of the CYP3 enzyme family, these results suggest that OD and SB may possess antimutagenic and antitumorigenic activity towards AFB1 through an inhibition of CYP3-mediated metabolism of AFB1. PMID- 8358289 TI - Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. AB - Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis. PMID- 8358290 TI - Pretreatment levels of CEA, CA 19-9, CA 50 and CA 72-4 in sera of patients with squamous cell carcinoma of the oesophagus. PMID- 8358291 TI - Structural engineering of the HIV-1 protease molecule with a beta-turn mimic of fixed geometry. AB - An important goal in the de novo design of enzymes is the control of molecular geometry. To this end, an analog of the protease from human immunodeficiency virus 1 (HIV-1 protease) was prepared by total chemical synthesis, containing a constrained, nonpeptidic type II' beta-turn mimic of predetermined three dimensional structure. The mimic beta-turn replaced residues Gly16,17 in each subunit of the homodimeric molecule. These residues constitute the central amino acids of two symmetry-related type I' beta-turns in the native, unliganded enzyme. The beta-turn mimic-containing enzyme analog was fully active, possessed the same substrate specificity as the Gly16,17-containing enzyme, and showed enhanced resistance to thermal inactivation. These results indicate that the precise geometry of the beta-turn at residues 15-18 in each subunit is not critical for activity, and that replacement of the native sequence with a rigid beta-turn mimic can lead to enhanced protein stability. Finally, the successful incorporation of a fixed element of secondary structure illustrates the potential of a "molecular kit set" approach to protein design and synthesis. PMID- 8358292 TI - In situ conversion of coproporphyrinogen to heme by murine mitochondria: terminal steps of the heme biosynthetic pathway. AB - Coproporphyrinogen oxidase (EC 1.3.3.3), protoporphyrinogen oxidase (EC 1.3.3.4), and ferrochelatase (EC 4.99.1.1) catalyze the terminal three steps of the heme biosynthetic pathway. All three are either bound to or associated with the inner mitochondrial membrane in higher eukaryotic cells. A current model proposes that these three enzymes may participate in some form of multienzyme complex with attendant substrate channeling (Grand-champ, B., Phung, N., & Nordmann, Y., 1978, Biochem. J. 176, 97-102; Ferreira, G.C., et al., 1988, J. Biol. Chem. 263, 3835 3839). In the present study we have examined this question in isolated mouse mitochondria using two experimental approaches: one that samples substrate and product levels during a timed incubation, and a second that follows dilution of radiolabeled substrate by pathway intermediates. When isolated mouse mitochondria are incubated with coproporphyrinogen alone there is an accumulation of free protoporphyrin. When Zn is added as a substrate for the terminal enzyme, ferrochelatase, along with coproporphyrinogen, there is formation of Zn protoporphyrin with little accumulation of free protoporphyrin. When EDTA is added to this incubation mixture with Zn, Zn protoporphyrin formation is eliminated and protoporphyrin is formed. We have examined the fate of radiolabeled substrates in vitro to determine if exogenously supplied pathway intermediates can compete with the endogenously produced compounds. The data demonstrate that while coproporphyrinogen is efficiently converted to heme in vitro when the pathway is operating below maximal capacity, exogenous protoporphyrinogen can compete with endogenously formed protoporphyrinogen in heme production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358293 TI - Effects of alanine substitutions in alpha-helices of sperm whale myoglobin on protein stability. AB - The peptide backbones in folded native proteins contain distinctive secondary structures, alpha-helices, beta-sheets, and turns, with significant frequency. One question that arises in folding is how the stability of this secondary structure relates to that of the protein as a whole. To address this question, we substituted the alpha-helix-stabilizing alanine side chain at 16 selected sites in the sequence of sperm whale myoglobin, 12 at helical sites on the surface of the protein, and 4 at obviously internal sites. Substitution of alanine for bulky side chains at internal sites destabilizes the protein, as expected if packing interactions are disrupted. Alanine substitutions do not uniformly stabilize the protein, either in capping positions near the ends of helices or at mid-helical sites near the surface of myoglobin. When corrected for the extent of exposure of each side chain replaced by alanine at a mid-helix position, alanine replacement still has no clear effect in stabilizing the native structure. Thus linkage between the stabilization of secondary structure and tertiary structure in myoglobin cannot be demonstrated, probably because of the relatively small free energy differences between side chains in stabilizing isolated helix. By contrast, about 80% of the variance in free energy observed can be accounted for by the loss in buried surface area of the native residue substituted by alanine. The differential free energy of helix stabilization does not account for any additional variation. PMID- 8358294 TI - Crystal structure to 2.45 A resolution of a monoclonal Fab specific for the Brucella A cell wall polysaccharide antigen. AB - The atomic structure of an antibody antigen-binding fragment (Fab) at 2.45 A resolution shows that polysaccharide antigen conformation and Fab structure dictated by combinatorial diversity and domain association are responsible for the fine specificity of the Brucella-specific antibody, YsT9.1. It discriminates the Brucella abortus A antigen from the nearly identical Brucella melitensis M antigen by forming a groove-type binding site, lined with tyrosine residues, that accommodates the rodlike A antigen but excludes the kinked structure of the M antigen, as envisioned by a model of the antigen built into the combining site. The variable-heavy (VH) and variable-light (VL) domains are derived from genes closely related to two used in previously solved structures, M603 and R19.9, respectively. These genes combine in YsT9.1 to form an antibody of totally different specificity. Comparison of this X-ray structure with a previously built model of the YsT9.1 combining site based on these homologies highlights the importance of VL:VH association as a determinant of specificity and suggests that small changes at the VL:VH interface, unanticipated in modeling, may cause significant modulation of binding-site properties. PMID- 8358295 TI - Primary structure of a photoactive yellow protein from the phototrophic bacterium Ectothiorhodospira halophila, with evidence for the mass and the binding site of the chromophore. AB - The complete amino acid sequence of the 125-residue photoactive yellow protein (PYP) from Ectothiorhodospira halophila has been determined to be MEHVAFGSEDIENTLAKMDDGQLDGLAFGAIQLDGDGNILQYNAAEGDITGRDPKEVIGKNFFKDVAP+ ++ CTDSPEFYGKFKEGVASGNLNTMFEYTFDYQMTPTKVKVHMKKALSGDSYWVFVKRV. This is the first sequence to be reported for this class of proteins. There is no obvious sequence homology to any other protein, although the crystal structure, known at 2.4 A resolution (McRee, D.E., et al., 1989, Proc. Natl. Acad. Sci. USA 86, 6533-6537), indicates a relationship to the similarly sized fatty acid binding protein (FABP), a representative of a family of eukaryotic proteins that bind hydrophobic molecules. The amino acid sequence exhibits no greater similarity between PYP and FABP than for proteins chosen at random (8%). The photoactive yellow protein contains an unidentified chromophore that is bleached by light but recovers within a second. Here we demonstrate that the chromophore is bound covalently to Cys 69 instead of Lys 111 as deduced from the crystal structure analysis. The partially exposed side chains of Tyr 76, 94, and 118, plus Trp 119 appear to be arranged in a cluster and probably become more exposed due to a conformational change of the protein resulting from light-induced chromophore bleaching. The charged residues are not uniformly distributed on the protein surface but are arranged in positive and negative clusters on opposite sides of the protein. The exact chemical nature of the chromophore remains undetermined, but we here propose a possible structure based on precise mass analysis of a chromophore binding peptide by electrospray ionization mass spectrometry and on the fact that the chromophore can be cleaved off the apoprotein upon reduction with a thiol reagent. The molecular mass of the chromophore, including an SH group, is 147.6 Da (+/- 0.5 Da); the cysteine residue to which it is bound is at sequence position 69. PMID- 8358296 TI - Crystal structure of activated tobacco rubisco complexed with the reaction intermediate analogue 2-carboxy-arabinitol 1,5-bisphosphate. AB - The crystal structure of activated tobacco rubisco, complexed with the reaction intermediate analogue 2-carboxy-arabinitol 1,5-bisphosphate (CABP) has been determined by molecular replacement, using the structure of activated spinach rubisco (Knight, S., Andersson, I., & Branden, C.-I., 1990, J. Mol. Biol. 215, 113-160) as a model. The R-factor after refinement is 21.0% for 57,855 reflections between 9.0 and 2.7 A resolution. The local fourfold axis of the rubisco hexadecamer coincides with a crystallographic twofold axis. The result is that the asymmetric unit of the crystals contains half of the L8S8 complex (molecular mass 280 kDa in the asymmetric unit). The activated form of tobacco rubisco is very similar to the activated form of spinach rubisco. The root mean square difference is 0.4 A for 587 equivalent C alpha atoms. Analysis of mutations between tobacco and spinach rubisco revealed that the vast majority of mutations concerned exposed residues. Only 7 buried residues were found to be mutated versus 54 residues at or near the surface of the protein. The crystal structure suggests that the Cys 247-Cys 247 and Cys 449-Cys 459 pairs are linked via disulfide bridges. This pattern of disulfide links differ from the pattern of disulfide links observed in crystals of unactivated tobacco rubisco (Curmi, P.M.G., et al., 1992, J. Biol. Chem. 267, 16980-16989) and is similar to the pattern observed for activated spinach tobacco. PMID- 8358298 TI - Characterization of the stable, acid-induced, molten globule-like state of staphylococcal nuclease. AB - Titration of a salt-free solution of native staphylococcal nuclease by HCl leads to an unfolding transition in the vicinity of pH 4, as determined by near- and far-UV circular dichroism. At pH 2-3, the protein is substantially unfolded. The addition of further HCl results in a second transition, this one to a more structured species (the A state) with the properties of an expanded molten globule, namely substantial secondary structure, little or no tertiary structure, relatively compact size as determined by hydrodynamic radius, and the ability to bind the hydrophobic dye 1-anilino-8-naphthalene sulfonic acid. The addition of anions, in the form of neutral salts, to the acid-unfolded state at pH 2 also causes a transition leading to the A state. Fourier transform infrared analysis of the amide I band was used to compare the amount and type of secondary structure in the native and A states. A significant decrease in alpha-helix structure, with a corresponding increase in beta or extended structure, was observed in the A state, compared to the native state. A model to account for such compact denatured states is proposed. PMID- 8358297 TI - Leucine 332 influences the CO2/O2 specificity factor of ribulose-1,5-bisphosphate carboxylase/oxygenase from Anacystis nidulans. AB - The role of Leu 332 in ribulose-1,5-bisphosphate carboxylase/oxygenase from the cyanobacterium Anacystis nidulans was investigated by site-directed mutagenesis. Substitutions of this residue with Met, Ile, Val, Thr, or Ala decreased the CO2/O2 specificity factor by as much as 67% and 96% for the Ile mutant in the presence of Mg2+ and Mn2+, respectively. For the Met, Ile, and Ala mutants in the presence of Mg2+, no loss of oxygenase activity was observed despite the loss of greater than 65% of the carboxylase activity relative to the wild-type enzyme. In the presence of Mn2+, carboxylase activities for mutant enzymes were reduced to approximately the same degree as was observed in the presence of Mg2+, although oxygenase activities were also reduced to similar extents as carboxylase activities. Only minor changes in Km(RuBP) were observed for all mutants in the presence of Mg2+ relative to the wild-type enzyme, indicating that Leu 332 does not function in RuBP binding. These results suggest that in the presence of Mg2+, Leu 332 contributes to the stabilization of the transition state for the carboxylase reaction, and demonstrate that it is possible to affect only one of the activities of this bifunctional enzyme. PMID- 8358299 TI - Refolding and proton pumping activity of a polyethylene glycol-bacteriorhodopsin water-soluble conjugate. AB - Bacteriorhodopsin (BR), from the purple membrane (PM) of Halobacterium halobium, was chemically modified with methoxypolyethylene glycol (m-PEG; molecular weight = 5,000 Da) succinimidyl carbonate. The polyethylene glycol-bacteriorhodopsin (m PEG-SC-BR33) conjugate, containing one polyethylene glycol chain, was water soluble. The secondary structure of the conjugate in water appeared partially denatured, but was shown to contain alpha-helical segments by circular dichroism spectroscopy. The isolated bacteriorhodopsin conjugate, with added retinal, was refolded in a mixed detergent-lipid micelle and had an absorption maximum at 555 nm. The refolded conjugate was transferred into vesicles that pumped protons, upon illumination, as efficiently as did native BR. Modification of the PM with m PEG did not alter the native structure or inhibit proton pumping, and therefore it is suggested that the glycol polymer is present as a moiety covalently linked to residues unnecessary for proton pumping and proper folding. The site of attachment of m-PEG was determined to be at either Lys 129 or Lys 159, with position Lys 129 the most probable site of attachment. The m-PEG-SC-BR33 could be stepwise refolded to the native conformation by the addition of trifluoroethanol to lower the dielectric constant, simulating the insertion of the BR into the phospholipid bilayer. PMID- 8358301 TI - Polarity of disulfide bonds. PMID- 8358300 TI - Cross-validation of protein structural class prediction using statistical clustering and neural networks. AB - We present an approach to predicting protein structural class that uses amino acid composition and hydrophobic pattern frequency information as input to two types of neural networks: (1) a three-layer back-propagation network and (2) a learning vector quantization network. The results of these methods are compared to those obtained from a modified Euclidean statistical clustering algorithm. The protein sequence data used to drive these algorithms consist of the normalized frequency of up to 20 amino acid types and six hydrophobic amino acid patterns. From these frequency values the structural class predictions for each protein (all-alpha, all-beta, or alpha-beta classes) are derived. Examples consisting of 64 previously classified proteins were randomly divided into multiple training (56 proteins) and test (8 proteins) sets. The best performing algorithm on the test sets was the learning vector quantization network using 17 inputs, obtaining a prediction accuracy of 80.2%. The Matthews correlation coefficients are statistically significant for all algorithms and all structural classes. The differences between algorithms are in general not statistically significant. These results show that information exists in protein primary sequences that is easily obtainable and useful for the prediction of protein structural class by neural networks as well as by standard statistical clustering algorithms. PMID- 8358302 TI - Fibronectin type III modules in the receptor phosphatase CD45 and tapeworm antigens. PMID- 8358303 TI - The contributions of Stein and Moore to protein science. PMID- 8358305 TI - [Experimental-clinical study of a dual-micron holmium laser]. PMID- 8358304 TI - [Formation of stabile complexes of myosin subfragment-1 with ADP and orthovanadate or beryllium fluoride in the presence of calcium ions]. PMID- 8358306 TI - [The effect of a glycoprotein from bone marrow (an amplifying protein) on the functional activity of growth factors]. PMID- 8358307 TI - [Rate of chromosome segregation in human-mouse somatic hybrids is controlled by murine genome]. PMID- 8358308 TI - [A radiation situation on the Kola Peninsula, Novaia Zemlia, Franz-Josef Land and in the Barents Sea water]. PMID- 8358309 TI - [Oligonucleotides forming highly stable, specific duplexes, their use as primers in sequencing and in the polymerase chain reaction]. PMID- 8358310 TI - [The effect of NMDA and quinolinic acid on cortical neurons of the rat brain]. PMID- 8358311 TI - [Reactions of reticulospinal neurons of the medulla oblongata on the stimulation of the inhibitory motion sites of the brain, thalamus, and frontal cortex]. PMID- 8358312 TI - [Cyclic peptide hepatotoxins from spring water cyanobacteria (blue-green algae) from blooming water sources in the Ukraine and in the European part of Russia]. PMID- 8358313 TI - [Xeno- and allotransplantation of insulin-producing tissues in the anterior eye chamber as a method of compensating for experimental diabetes]. PMID- 8358314 TI - [The effect of specific formations in mouth corners on physiologo-morphological parameters of the adult Campbell hamster (Phodopus Campbelli, Thomas, 1905)]. PMID- 8358315 TI - [Visual radiation fibers regenerate after replacing the visual cortex with a neocortical transplant]. PMID- 8358316 TI - [Integration of hepatitis B virus DNA into the human neuroblastoma cell genome]. PMID- 8358317 TI - [Expression of heat shock proteins in mycoplasma]. PMID- 8358318 TI - [Structure of the anal gland of the Mongolian woodchuck]. PMID- 8358319 TI - [Effect of synthesizing molecules of double-stranded RNA in transgenic tobacco plants on resistance to tobacco mosaic virus]. PMID- 8358320 TI - [Morphofunctional adaptation of the Galliformes cecum to vegetable feedstuffs]. PMID- 8358321 TI - [Structure and function of the hemiglandular and discoglandular stomachs of field mice (Rodentia, Clethrionomys)]. PMID- 8358322 TI - Microheterogeneity in O-type sugar chains of carbohydrases secreted by Asp. awamori. AB - This paper deals with microheterogeneity in the structure of O-linked sugars of carbohydrases secreted by Asp. awamori, namely glucoamylase, alpha-galactosidase and alpha-glucosidase. Microheterogeneity was found to be related both to post secretion deglycosylation and to changes in transferase activity induced by the differences in culturing conditions. PMID- 8358323 TI - Adsorption of glucoamylase from Asp. awamori X-100/D27 on cell walls. AB - Upon secretion, the major form of glucoamylase from Asp. awamori adsorbs on fungal cell walls. Its substrate binding site showing affinity for alpha-1-4 and alpha-1-6 wall glucans is responsible for adsorption. The minor form in which this site is absent has no sorption ability for cell walls. PMID- 8358325 TI - New observations on proteases of the human hookworm Necator americanus. AB - Two protease populations have been identified in the somatic products of adult Necator americanus. One population (158, 138, 34 and 31 kDa) loses, whereas the other population (107, 74, 51 and 20 kDa) retains, its proteolytic activity after elution from substrate gels. The present study warns that hookworm proteases may oligomerise and/or lose their activity under the conditions necessary for their purification. We suggest that following assessment of protease activity on substrate gels, the protease of interest should be eluted from plain gels; their isolation from substrate gels may lead to a reduced or no yield. PMID- 8358324 TI - Structure and properties of the 26S protease complex from chick skeletal muscle. AB - The 26S protease complex was purified from chick skeletal muscle and shown to consist of unusually heterogeneous 21-140 kDa polypeptides, including the 21-32 kDa subunits of the 20S proteasome. Electron microscopic analysis revealed that the 26S complex may have a symmetric morphology with two large rectangular terminal domains attached to a thinner central 20S proteasome domain. The 26S complex was capable of degrading the peptide substrates of the 20S proteasome, including Suc-LLVY-AMC, N-Cbz-LLE-NA and N-Cbz-ARR-MNA. The two enzyme complexes showed similar sensitivities to various site-specific protease inhibitors, although their sensitivities to SDS were differed from each other. Immunoprecipitation with anti-26S complex antibody reduced peptide hydrolysis by the 20S proteasome. Similarly, anti-20S proteasome antibody inhibited peptide hydrolysis by the 26S complex. These results demonstrate that the 26S protease complex contains the 20S proteasome as a functional and structural component. PMID- 8358326 TI - Dual role of free fatty acids in regulation of mitochondrial L-glycerol-3 phosphate dehydrogenase. AB - In brown adipose tissue mitochondria, the influence of free fatty acids on FAD linked L-glycerol-3-phosphate dehydrogenase was investigated using either hydrophilic or hydrophobic electron acceptors. The apparent kinetic parameters were determined for substrate and electron acceptors in the presence of different concentrations of oleic acid. In contrast to the L-glycerol-3-phosphate dehydrogenase enzyme from mitochondrial hyperthyroid rat liver, the brown adipose tissue enzyme shows only a single detectable L-glycerol-3-phosphate binding site. The inhibition is of competitive type for L-glycerol-3-phosphate using either hydrophilic or hydrophobic electron acceptors, while for electron acceptors non competitive or uncompetitive inhibition was determined, respectively. PMID- 8358327 TI - Characterisation of 2S albumin with nutritionally balanced aminoacid composition from the seeds of Chenopodium album and its antigenic homology with seed proteins of some Chenopodiaceae and Amaranthaceae species. AB - The low molecular weight 2S albumin protein of Chenopodium album seeds has been isolated and characterized with respect to its subunit structure by SDS-PAGE and antigenic homology with low molecular weight seed storage proteins of several other phylogenetically related species by immunoprecipitation and Western blotting. These studies revealed the existence of antigenically homologous proteins of similar molecular weights in seeds of some other members of Chenopodiaceae and Amaranthaceae. However, Chenopodium 2S albumin is antigenically unrelated to low mol.wt. albumins of dicots belonging to other families. It has a nutritionally balanced aminoacid composition in respect of essential aminoacids. PMID- 8358328 TI - Influence of palm oil or its tocotrienol-rich fraction on the lipid peroxidation potential of rat liver mitochondria and microsomes. AB - The effect of palm oil, a widely used vegetable oil, rich in tocotrienols, on peroxidation potential of rat liver was examined. Long-term feeding of rats with palm oil as one of the dietary components significantly reduced the peroxidation potential of hepatic mitochondria and microsomes. As compared to hepatic mitochondria isolated from rats fed control or corn oil-rich diet, those from palm oil-fed group showed significantly less susceptibility to peroxidation induced by ascorbate and NADPH. However, in microsomes, only NADPH-induced lipid peroxidation was significantly reduced in rats fed palm oil rich-diet. Though the accumulation of thiobarbituric acid reactive substances during ascorbate-induced lipid peroxidation in mitochondria from rats fed corn oil-rich diet supplemented with tocotrienol-rich fraction (TRF) of palm oil was similar to that of control rats, the initial rate of peroxidation was much slower than those from control or corn oil fed diets. Our in vitro studies as well as analyses of co-factors related to peroxidation potential indicated that the observed decrease in palm oil-fed rats may be due to increased amount of antioxidants in terms of tocotrienol as well as decrease in the availability of substrates for peroxidation. PMID- 8358329 TI - The mechanism(s) of the alcohol-induced impairment in glycogen synthesis in oxidative skeletal muscles. AB - Ethanol is known to acutely inhibit glucose-stimulated glycogen deposition in skeletal muscles in the rat. This effect is selective for oxidative as opposed to non-oxidative muscles. This paper explores the biochemical basis for this selective impairment in muscle glycogen metabolism. 4-Methylpyrazole, a potent inhibitor of alcohol dehydrogenase, potentiated the ethanol-mediated impairment in glycogen deposition in oxidative muscles and was associated with abnormalities in glycogen deposition in non-oxidative muscles. By contrast, disulfiram, a potent inhibitor of aldehyde dehydrogenase had no effect on the ethanol-mediated impairment in glycogen deposition in both oxidative and non-oxidative muscles. The implication is that it is the ethanol molecule itself, and not one of its metabolites (acetaldehyde, acetate, excess NADH), that mediates the defect in glycogen metabolism. PMID- 8358330 TI - Increased platelet aggregation and fatty acid oxidation in diabetic rats. AB - The effects of diabetes on fatty acid oxidation in platelets was determined in streptozotocin-induced diabetic rats. In platelets isolated from diabetes, the oxygen consumption which reflects mainly the degree of fatty acid oxidation and ADP- and thrombin-induced aggregation were increased as compared to non-diabetic rat platelets. Carnitine palmitoyltransferase I (CPT I), the rate-limiting enzyme for fatty acid oxidation, in platelets obtained from diabetes showed a higher Vmax for palmitoyl-CoA and an increased I50 (concentration giving 50% inhibition of CPT I activity) for malonyl-CoA inhibition. These changes observed in fatty acid oxidation in platelets derived from diabetes returned to the control levels after insulin therapy. When platelets were stimulated with thrombin, platelet CPT I activity increased over time in both diabetic and non-diabetic rats. From these findings, fatty acid oxidation in platelets, as in the liver, is likely to be regulated by insulin and both increased CPT I activity and decreased sensitivity to malonyl-CoA inhibition are attributable to enhanced platelet fatty acid oxidation in diabetic rats. PMID- 8358331 TI - Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. AB - The synthetic C-terminal peptide fragment of human growth hormone, Leu-Arg-Ile Val Gln-Cys-Arg-Val-Ser-Glu-Gly-Ser-Cys-Gly-Phe (hGH 177-191), was shown to have antilipogenic activity identical with that of the intact molecule of human growth hormone (hGH). No significant lipolytic effect of hGH 177-191 was found as determined by the rate of glycerol release from epididymal fat pads of the peptide-treated rats. The results support the suggestion that the functional domain responsible for the antilipogenic activity of hGH resides in the C terminal region of the molecule and that the main physiological effect of hGH in lipid metabolism is at the level of lipogenesis. PMID- 8358332 TI - Effects of tumour necrosis factor-alpha on the enzymatic activities related to glucose metabolism. AB - The effects of an intravenous administration of a single dose (100 micrograms/kg bw) of tumour necrosis factor-alpha (TNF, cachectin) on in vivo glucose oxidation and on several enzymatic activities related with glucose metabolism both in rat liver and skeletal muscle were studied. The treatment with the cytokine induced an increase in the oxidation of glucose, the differences being significant from minute 30. In contrast, TNF did not induce any change on the activities of glucokinase, hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase, although significant increase in the activity of muscle phosphofructokinase was observed. PMID- 8358333 TI - Chronic tumour necrosis factor-alpha treatment modifies protein turnover in rat tissues. AB - Chronic TNF treatment for 8 days resulted in an increased protein turnover in most of the tissues studied. The increased turnover could be observed in both the synthetic and degradation fractional constants; however, in the majority of the tissues (muscle, diaphragm, heart, kidneys, lungs and brown adipose) the increase in Kd was higher than that of Ks resulting thus in a reduced protein accumulation (Ka). In contrast, chronic TNF treatment resulted in an increased brain protein accumulation. The data presented suggest that the cytokine could be involved in tissue wasting in pathological states such as sepsis and malignancy. PMID- 8358334 TI - The distribution of aldose and aldehyde reductases in different regions of human and bovine kidney. AB - Human and Bovine kidney aldose and aldehyde reductases from cortex, medulla and papilla have been purified by DE-52 column chromatography or chromatofocusing and have been biochemically characterized. In both human and bovine kidney, cortex contains only aldehyde reductase and papilla aldose reductase. Medulla however, contains aldose as well as aldehyde reductase. PMID- 8358335 TI - Purification of superoxide dismutase from placental haemolisate blood: a simple and efficient method. AB - Superoxide dismutase functions as a scavenger of superoxide radical protecting living organisms. This enzyme has potential use as anti-inflammatory or anti reperfusion injury drug. Here we present a simple and efficient SOD purification method from human placental blood. Superoxide dismutase from clarified haemolysed placental blood after chloroform and ethanol treatment was purified by DEAE Sepharose, Phenyl-Sepharose chromatographies and cross flow ultrafiltration. The purified product is 98% pure by SDS-PAGE with 71% yield and specific activity of 2.8 x 10(5) U/mg protein. PMID- 8358336 TI - Comparison of changes in the uptake and mucosal processing of iron in riboflavin deficient rats. AB - Riboflavin deficiency in rats resulted in a reduction in the transfer of 59Fe from an intragastric dose to plasma compared to age-matched or weight-matched controls. The uptake of iron by brush-border membrane vesicles made from intestinal mucosa of riboflavin-deficient rats was much less than identically prepared vesicles from control groups. Although the mucosal content of 59Fe was smaller in riboflavin-deficient rats thirty minutes after dosing, the relative distribution of 59Fe between the mucosal iron-binding proteins, ferritin and transferrin, was not changed compared to the control groups. These studies suggest that the impairment in iron absorption in riboflavin deficiency is primarily the result of a reduced uptake of iron into the mucosal cell and not a redistribution of iron between iron-binding proteins inside the mucosal cell. PMID- 8358338 TI - 4-Hydroxyaminoquinoline 1-oxide can convert the Z-form of poly(dG-m5dC).poly(dG m5dC) back to B-form-DNA. AB - Reactions between the chemical carcinogen 4-hydroxyaminoquinoline 1-oxide (4HAQO) and poly(dG-dC).poly(dG-dC), poly(dG-m5dC).poly(dG-m5dC) and poly(dG br5dC).poly(dG-br5dC) were studied under B-form and Z-form conformation conditions. 4HAQO bound covalently to both B-form and Z-form-DNA. The extent of the B-form to Z-form-DNA transition was diminished by 4HAQO, as inferred by spectroscopic methods. Moreover, conversion of the Z-form-DNA back to a right handed DNA close to the B-form was observed with this carcinogen. PMID- 8358337 TI - Translocation of human platelet calpain-I. AB - Intracellular localization of calpain (calcium dependent cysteine proteinase) was studied in resting or activated human platelets. When stimulated with 2 U/ml thrombin, approximately 40% of total cellular calpain activity and 25% of antigen translocated mainly to the intracellular membrane fractions with autolytic activation. Translocation of calpain was completely abolished by the addition of EDTA to the sonication medium. However an endogenous calpain inhibitor (calpastatin) activity was not detected in the membrane fractions both in resting and in thrombin stimulated platelets. Translocation of calpain was also observed in the platelets stimulated with ionomycin, collagen or phorbor myristate acetate (PMA). These data suggest that cytosolic calpain reversibly translocates to the intracellular membranes during platelet activation without an interference by calpastatin. PMID- 8358339 TI - Effect of aging on insulin regulation of fructose 2,6-bisphosphate metabolism in human fibroblasts. AB - Fructose 2,6-bisphosphate (Fru-2,6-P2) content in human fibroblasts is under hormonal control and is strictly related to glycolytic flux. In the present study it has been examined whether aging process is accompanied with an impairment in the control exerted by insulin on the metabolite content. Upon insulin stimulation old fibroblasts show a reduced increase in Fru-2,6-P2 content and glycolytic flux. Similarly, 6-phosphofructo-2-kinase (PFK-2) activity in old fibroblasts is increased at a lesser extent by insulin treatment, suggesting that an impairment at post-receptor level in the signalling pathway of insulin might occur with aging. In addition in unstimulated senescent fibroblasts PFK-2 displays higher activity and reduced Km for substrate, suggesting either that during senescence PFK-2 undergoes a post-translational modification or that a different PFK-2 isoenzyme is expressed. PMID- 8358340 TI - N-(2-hydroxybenzyl)-omega-amino carbonic acids and their derivatives as tools for biochemical and biophysical investigations. AB - We propose N-(2-hydroxybenzyl)-omega-amino carbonic acids (An) as multifunctional probes for fatty acid metabolism studies. Multifunctionality could be achieved by introduction of different isotopes into An molecule. Deuteration of An results in probes for 2H-NMR membrane studies. Introduction of radioactive iodine and bromine isotopes into An gives diagnosticums for gamma-tomography and PET. AnI and AnBr are fluorescence quenchers usable for membrane studies. This multifunctionality of An derivatives is valuable because they participate in such metabolic pathways of fatty acids as beta-oxidation and inclusion into lipids. They can also inhibit natural FA oxidation. PMID- 8358341 TI - Preclinical evaluation of intravenously administered 111In- and 90Y-labeled B72.3 immunoconjugate (GYK-DTPA) in beagle dogs. AB - B72.3, a monoclonal antibody with reactivity against human adenocarcinomas was obtained from the Cytogen Corporation in the form of an immunoconjugate coupled with linker-chelator GYK-DTPA by using proprietary carbohydrate directed site specific chemistry. The immunoconjugate was radiolabeled with indium-111 or yttrium-90. A preclinical analysis was performed in 10 normal beagle dogs. The pharmacokinetics of intravenously administered indium- and yttrium-labeled immunoconjugates were compared serially in blood, bone marrow and urine samples. Compared to 90Y less of the 111In label ended up in urine and more was found in blood and bone marrow. Indium-labeled B72.3 GYK-DTPA had relatively higher uptake in most glandular tissues than 111In-labeled antiferritin immunoconjugate. Bone marrow toxicity was the dose limiting side effect after intravenous infusion of 90Y-labeled B72.3 GYK-DTPA. Toxicity was also observed in the liver but not in other organ systems. Recently other investigators obtained similar results with these immunoconjugates in human patients. A preclinical pharmacokinetic analysis of radioimmunoconjugates in beagle dogs provided useful information regarding bone marrow toxicity, liver toxicity and in vivo instability of the immunoconjugate. Data suggest that for future trials in human patients, a more stable chelated immunoconjugate for yttrium is needed to achieve less liver uptake and a better correlation with the 111In-labeled product than the 90Y labeled B72.3 GYK-DTPA used in this investigation. PMID- 8358342 TI - Fractionated intravenous administration of 90Y-labeled B72.3 GYK-DTPA immunoconjugate in beagle dogs. AB - B72.3, a monoclonal antibody with reactivity against human adenocarcinomas, was coupled with linker-chelator GYK-DTPA using carbohydrate mediated conjugation chemistry and radiolabeled with yttrium-90. Single and double intravenous injections of radioimmunoconjugate were compared for acute and late normal tissue toxicity in 15 beagle dogs. The second injection was given 4 or 8 days after the first. Pharmacokinetics of the radioimmunoconjugate in blood, bone marrow and urine were similar for first and second injections. Only bone marrow (acute) and liver (late) toxicity were observed. Both liver and bone marrow toxicity were decreased by fractionation of the injections. After double injections, the total equitoxic dose was 15 and 60% higher for bone marrow and liver toxicity, respectively. The mechanisms of normal tissue protection offered by fractionated radioimmunoglobulin therapy (RIT) remain to be defined. Fractionated RIT will have a better therapeutic ratio than single injection RIT, if antitumor effects appear to be less susceptible to fractionation than normal tissues. PMID- 8358343 TI - Quantitation of thrombogenicity of hemodialyzer with technetium-99m and indium 111 labeled platelets. AB - The platelet thrombogenicity of a hemodialyzer was quantified with 99mTc- and 111In-labeled platelets. The platelets collected from blood of Beagle dogs, Yorkshire pigs and human volunteers were labeled with 111In-tropolone (detergent free) and 99mTc-HMPAO. Hemodialysis was performed with a hollow-fiber dialyzer (HFD) in a flow-loop, the temperature of which was maintained at 37 degrees C, with flow-rates of 7, 150 and 270 mL/min; after dialysis, the HFD radioactivity was measured with an ionization chamber and imaged with a gamma-camera. The radioactivity of samples of hollow-fibers taken from the top, middle and bottom of the dialyzer was determined with a gamma-counter. The mean values of hemodialyzer-adherent platelet radioactivity were calculated for both radionuclides. The canine platelets were found to be more thrombogenic than porcine and human platelets. The adhesivity of porcine platelets to the biomaterial (cellulose-acetate) of the dialyzer approximated that of human platelets. The 99mTc label underestimated the thrombus formation (P < 0.01). The dynamic processes of thrombosis and embolization from the hemodialyzer resulted in the large standard deviations around the mean values of the adherent thrombus. In spite of this limitation of the dynamic pathology, the quantitation of comparative thrombogenicity with 111In- and 99mTc-labeled platelets suggests that both radionuclides could be used for measurement of device-induced thrombogenicity and may provide an estimation of prosthesis-induced thrombogenicity of human platelets from animal studies. PMID- 8358344 TI - A pilot study using 99mTc to measure lead and platinum in the human kidney. AB - A pilot study has been conducted to investigate the hypothesis that the chemotherapeutic drug, cisplatinum, can mobilize skeletal lead. In vivo measurements of lead and platinum in the kidney of chemotherapy patients were performed with the technique of x-ray fluorescence, using 99mTc in a backscatter geometry. The results of the pilot study were inconclusive; the majority of patients exhibited no evidence of kidney lead at the level of system sensitivity, and negligible blood and urine lead levels. PMID- 8358346 TI - In vitro and in vivo testing of the dopamine D1 ligand [123I]SCH 23982 with respect to its potential application in SPET investigations. AB - [123I]SCH 23982, a dopamine D1 ligand, was labelled in a large scale process and then tested in vitro for binding to rat brain sections and membranes. Because of the promising values of KD = 1.5 x 10(-10) M and Bmax = 0.7 x 10(-11) mol/g, in vivo evaluation was performed on rats and normal volunteers to test its possible usefulness for SPET imaging. In competition experiments, a higher binding in the presence of sulpiride was found while ketanserin displaced [123I]SCH 23982 only at a 10,000-fold excess. Differences between rats and men were seen with respect to their metabolism. SPET investigations failed because the washout of [123I]SCH 23982 was too rapid. PMID- 8358345 TI - Evaluation of the monoamine uptake site ligand [123I]methyl 3 beta-(4-iodophenyl) tropane-2 beta-carboxylate ([123I]beta-CIT) in non-human primates: pharmacokinetics, biodistribution and SPECT brain imaging coregistered with MRI. AB - The in vivo properties of a new radioiodinated probe of the dopamine and serotonin transporter, [123I]methyl 3 beta-(4-iodophenyl)tropane-2 beta carboxylate ([123I]beta-CIT) were evaluated in baboons and vervet monkeys. The labeled product was prepared in 65.2 +/- 2.8% yield (mean +/- SEM; n = 18) by reaction of the tributylstannyl precursor with [123I]NaI in the presence of peracetic acid followed by high pressure liquid chromatography (HPLC) purification to give a product with radiochemical purity of 97.5 +/- 0.5% and specific activity of 500-1200 Ci/mmol. After intravenous administration, whole brain activity peaked at 6-10% injected dose within 1 h post injection (p.i.) and washed out in a biphasic manner with clearance half-lives of 1-2 and 7-35 h for the rapid and slow components, respectively. Excretion occurred primarily through the hepatobiliary route, with about 30% of the injected dose appearing in the GI tract after 5 h. Estimates of radiation absorbed dose gave 0.01, 0.1, 0.2 and 0.03 mGy/MBq to the brain, gall bladder wall, lower large intestine wall and urinary bladder wall, respectively. High resolution SPECT imaging in a baboon demonstrated high uptake of tracer in the region of the striatum (striatum:cerebellum ratio 4.0), in the hypothalamus (ratio 2.6) and in a midbrain region comprising raphe, substantia nigra and superior colliculus (ratio 2.0), with regional brain uptakes measured at 210 min p.i. of [123I]beta-CIT. The anatomical locations of the regions on the SPECT image were confirmed by coregistration with MRI. Plasma metabolites and pharmacokinetics were analyzed in baboons and vervets by ethyl acetate extraction and HPLC. The major metabolite was a polar, non-extractable fraction, which increased to > 50% of the plasma activity by 30-45 min p.i. A minor lipophilic (extractable) metabolite was also observed, increasing to about 4% at 2-3 h p.i. The plasma protein bound fraction, determined by ultrafiltration, was 74.8 +/- 1.4% (n = 6). The arterial input function was characterized by the sum of three exponential terms with half-lives of 0.3-1.7, 9.7-24.9 and 77-166 min, respectively, for the concentration of free parent compound. [123I]beta-CIT promises to be a useful marker for SPECT study of the monoamine uptake system in primate brain. PMID- 8358347 TI - In vivo instability of reduction-mediated 99mTc-labeled monoclonal antibody. AB - A murine monoclonal antibody that reacts with human osteogenic sarcoma (OST7) was reduced and directly labeled with 99mTc without any loss of immunoreactivity. No fragmentation of the antibody was detected by high performance liquid chromatography after the labeling. However, SDS-PAGE analysis of the labeled antibody demonstrated the presence of low molecular weight species. Although more than 95% of the radioactivity remained bound at the antibody after incubation with human serum for 24 h, 99mTc-labeled OST7 was cleared faster from the circulation than 125I-labeled OST7 or 111In-labeled OST7 in mice. Urinary and fecal excretion of 99mTc were higher than those of 125I. When the 125I-labeled antibody was dual-labeled with 99mTc, the blood clearance of 99mTc was faster than that of 125I, suggesting release of 99mTc from the antibody in vivo. 99mTc labeled OST7, however, gave a higher tumor-to-blood ratio than 125I- or 111In labeled OST7 in mice bearing human osteogenic sarcoma. The 99mTc-labeled antibody prepared by the direct method was unstable in vivo, but retained a good tumor targeting ability. PMID- 8358348 TI - Synthesis of (+/-)-[18F]BMY 14802, its enantiomers and their anatomical distributions in rodents. AB - A potential antipsychotic drug, BMY 14802 was labeled with 18F and its distribution in rodents was studied. No-carrier-added (NCA) (+/-)-[18F]BMY 14802 (5) was synthesized by two methods in 5-10% radiochemical yield in a synthesis time of 130-140 min from EOB with a specific activity of 0.5-1.5 Ci/microM. (+)- and (-)-[18F]BMY 14802 was synthesized by the chiral reduction of alpha-(4 [18F]fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-b utanone (4) with chiral reducing agent, (+)- and (-)-beta-chlorodiisopinocampheylborane [(+)- and (-)-DIP chloride] in 6-10% radiochemical yield in a synthesis time of 150 min from EOB. Animal studies in mouse and in rat revealed that the distribution of 5 in each tissue was high at 5 min, the radioactivity then declined rapidly in all tissues studied except in the liver and in the small intestine. The radioactivity in the femur did not increase with time indicating in vivo defluorination may not occur. The uptakes of (+/-)-[18F]BMY 14802 and its enantiomers, (+)- and (-) [18F]BMY 14802 in rat cerebellum, brain stem, hippocampus and spinal cord were similar and were significantly reduced by prior treatment of rat with haldol. This suggests that (+/-)-[18F]BMY 14802 and its enantiomers bind to sigma receptors in a similar fashion. PMID- 8358349 TI - Simplified measurement of protein-bound iodine with epithermal neutron activation analysis. AB - A refined method for the measurement of protein-bound iodine (PBI) in blood serum was demonstrated by the use of epithermal neutron activation analysis (ENAA). PBI in ammonium sulfate-precipitated serum protein, after epithermal neutron activation, was determined by high resolution gamma-ray spectrometry. From our results, the PBI concentration was 67.8 +/- 2.2 ng/mL. Good agreement was obtained with published data, ranging from 40 to 80 ng/mL, which had been obtained using different analytical techniques. The validity of these techniques for PBI has been born out by a very good accuracy and simplicity without temperature dependence. PMID- 8358350 TI - Studies of quality control of 99mTc-labelled macroaggregated albumin--Part 1. Aggregation of non-mercaptalbumin and its conformation. AB - The aggregative condition of albumin was investigated using bovine serum albumin (BSA) as a model for quality control of 99mTc-macroaggregated albumin (99mTc MAA). Uniformalized aggregates were obtained from the oxidized non-mercapt-type of BSA by heating. The size of the aggregates was affected by the pH and the types of buffer solutions used as well as the concentrations of albumin and buffers. The beta form structure of the albumin was more stable on heating and this may contribute to its aggregation. Aggregation of oxidized non mercaptalbumin afforded a portion of smaller sized particles in MAA, this being an inappropriate factor for scintiscanning of lungs. Our results suggest that it is necessary to remove oxidized type albumin from human serum albumin as the starting material, in order to prepare MAA with a uniform and larger particle size. PMID- 8358351 TI - Chloramine-T induced binding of monoclonal antibody B72.3 to concanavalin-A. AB - The effects of chloramine-T (CT) on monoclonal antibody B72.3 were studied with particular reference to Con-A lectin binding. After exposure to chloramine-T concentrations from 0.8 to 4.0 mg/mL (115-574 mol CT/mol B72.3), B.72.3 showed progressive binding to agarose-linked Con-A. This behavior was paralleled by decreasing immunoreactivity and increasing fragmentation and aggregation of B72.3 demonstrated by SDS-PAGE and size exclusion HPLC. PMID- 8358352 TI - Analysis of urine samples from metastatic bone cancer patients administered 153Sm EDTMP. AB - 153Sm-EDTMP is currently undergoing clinical evaluation as a radiotherapeutic agent for the relief of pain associated with cancer metastatic to bone. These clinical studies have demonstrated biodistributions similar to those seen earlier in animals, namely, rapid clearance from blood, selective uptake in bone and in particular metastatic bone lesions. The radioactivity not deposited in bone is cleared through the kidneys into the urine. In this study, urine samples collected from 9 patients injected with 153Sm-EDTMP underwent complexation analysis via Pharmacia SP-Sephadex C25 cation exchange chromatography. The results showed 96.9 +/- 1.7% of the radioactivity in the urine to be present as a complex of 153Sm. An HPLC method was developed and it was demonstrated that different complexes of 153Sm could be separated. A non-radioactive analytical standard of the Sm-EDTMP chelate was synthesized, characterized and shown to have the same HPLC retention profile as the 153Sm-EDTMP drug product. HPLC analysis was performed on six urine samples and in each case a single radioactivity peak with an elution profile the same as that of a 153Sm-EDTMP standard was observed. These results indicate that the 153Sm-EDTMP chelate is excreted intact in the urine of patients. PMID- 8358353 TI - Pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin and biotin. AB - The extraordinary high affinity of avidin and streptavidin for biotin may be exploited in a two-step approach for delivering radiolabeled biotin derivatives suitable for imaging and therapy to target-bound streptavidin or avidin conjugated monoclonal antibodies (MAbs). The in vivo pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin (SA) and DTPA-biocytinamide (DTPA-biotin) were studied in the rabbit and dog. SA circulated in the blood similar to other 60 kDa proteins, avidin cleared immediately and DTPA-biotin exhibited plasma clearance by glomerular filtration. PMID- 8358354 TI - Preparation of [1-11C]dopamine, [1-11C]p-tyramine and [1-11C]m-tyramine. Autoradiography and PET examination of [1-11C]dopamine in primates. AB - A method for no-carrier-added 1-11C-labelling of 3-hydroxy-, 4-hydroxy- and 3,4 dihydroxy-substituted phenethylamines is described. [11C]Dopamine, [11C]p tyramine and [11C]m-tyramine were prepared from on-line produced [11C]nitromethane. Condensation of [11C]nitromethane with various protected and unprotected benzaldehydes was investigated. A one-pot two-step reduction of the substituted 11C-labelled nitrostyrene intermediates, gave after hydrolysis and reversed-phase semi-preparative HPLC-purification the corresponding labelled amines in a total radiochemical yield of 8-20% (based on [11C]CO2 and decay corrected). The total synthesis time was 45-50 min with a specific radioactivity of 400-1000 Ci/mmol (15-37 GBq/mumol). The radiochemical purity was higher than 98% [11C]Dopamine was used for in vitro autoradiography on human post-mortem brain sections and for positron emission tomography (PET) on Cynomolgus monkeys. Autoradiographic examination of [11C]dopamine binding on human brain section post mortem demonstrated specific binding in the caudate putamen and the substantia nigra, regions with a dense dopaminergic innervation. Some binding was also seen in the globus pallidum, nucleus ventralis of the thalamus and in nucleus dentatus of the cerebellum, regions where the dopaminergic innervation is very low. In PET examinations of [11C]dopamine binding in Cynomolgus monkeys there was a high uptake of radioactivity in the pituitary, the kidneys and the heart. Any passage of [11C]dopamine across the blood-brain barrier could not be demonstrated. In human PET studies [11C]dopamine has potential as a radioligand for examination of the myocardium, pituitary and kidneys. PMID- 8358355 TI - Dose-dependent biodistribution of [153Gd]Gd(acetate)n in mice. AB - [153Gd]Gd(acetate)n was administered i.v. to mice to study the effect of dose on the distribution of free Gd. Distribution from blood was slow with the majority of the Gd distributing in the liver. Gd saturated in bone. Heart, lungs, kidneys, brain and skeletal muscle exhibited time-dependent decreases in Gd concentration. Gd that washed out of heart, lungs, kidneys and/or muscle redistributed in liver, spleen and femur. These results indicate a complex dose- and time-dependent tissue distribution for Gd and emphasize the importance of eliminating unchelated free Gd as a contaminant in Gd-chelates before testing in biodistribution experiments. The long-term residual accumulation of Gd suggests the need to minimize Gd-chelate dissociation in vivo. PMID- 8358356 TI - Radioassays of yttrium-90 used in nuclear medicine. AB - Yttrium-90 radioassays are required in nuclear medicine at the gigabecquerel activity level (GBq) for measuring injected activity, and at the becquerel level for measuring individual tissue samples in biodistribution studies. A method of standardizing 90Y for activity using high-efficiency liquid-scintillation counting is described. Solution standards were used to establish the calibration factors for commercial radionuclide calibrators. Detection efficiencies are also presented for liquid-scintillation counting, NaI(T1) bremsstrahlung counting and Cerenkov counting. PMID- 8358358 TI - Continuing education. PMID- 8358357 TI - Radiopharmacology of inhaled 133Xe in skeletal sites containing deposits of Gaucher cells. AB - Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of inhaled 133Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a gamma-camera interfaced to a computer system. All patients rebreathed 133Xe gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered "dose"). There was essentially no 133Xe uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Skeletal Gaucher deposits released the 133Xe at a greater rate relative to soft tissue. PMID- 8358359 TI - Screening for psychological problems in temporomandibular disorder patients. AB - Research efforts have been directed to determine whether temporomandibular disorder (TMD) patients have psychological problems and whether these factors influence treatment outcome. Because there is no consensus about the best way to quickly assess psychological problems in TMD patients, this study was designed to evaluate a simple method for identifying psychological factors that may need to be addressed as part of a comprehensive treatment program. This method involved having TMD patients systematically rate themselves, using a brief screening questionnaire, for the presence or absence of psychological problems. These ratings were then compared to results from extensive psychological testing. Sensitivity, specificity, and ordinal rank-based association model analyses showed moderate to strong associations between patients' ratings and the corresponding psychometric measures. These results provide evidence that the brief self-ratings of psychological factors utilized in this study may be a useful first step to screening for psychological difficulties in TMD patients. PMID- 8358360 TI - Myogenous or arthrogenous limitation of mouth opening: correlations between clinical findings, MRI, and clinical outcome. AB - The reproducibility and predictive power of MRI diagnosis was evaluated in a group of 70 patients with limited mouth opening. The predictive reliability of the MRI findings was assessed by comparing the images with a final clinical diagnosis that was based on the initial clinical diagnosis, adjusted and refined, when possible, by findings made during the treatment period (conservative treatment in 51 patients, conservative and surgical treatment in 19 patients). The overall reproducibility of the MRI interpretation by the radiologist appeared very good. The predictive reliability was excellent for normal disc position and fair for anterior disc displacement with reduction. For disc displacement without reduction, however, the predictive power was questioned because of false-positive MRI findings. PMID- 8358362 TI - Clinical utility of mandibular movement ranges. AB - The range of mandibular movements was studied on 600 randomly selected people. Mandibular mobility varied widely from subject to subject. There were considerable age and sex differences but no differences were found between the mobility values of persons who were functionally healthy and those with dysfunctions. These factors make it difficult to construct cutoff values that reflect normalcy in mandibular mobility and thus render the clinical utility of such values questionable. The use of age- and sex-corrected border values for mandibular mobility is proposed. The clinical utility of patients' opinions concerning mouth-opening capacity is stressed. On the basis of statistically significant differences, the use of different border values for the protrusive and laterotrusive movements seems to be necessary. PMID- 8358361 TI - Association between malocclusion and temporomandibular disorders in orthodontic patients before treatment. AB - The association between malocclusion and the prevalence of temporomandibular disorders (TMD) was studied in an orthodontic patient population before orthodontic treatment was started. A total of 305 patients, 232 with general malocclusion and 73 who also had cleft lip or palate, were given a questionnaire about the subjective symptoms of TMD. Clinical examinations for type of malocclusion and TMD signs were also conducted. No significant differences in the prevalence of TMD were observed between the sexes or between the two patient groups. Temporomandibular joint sounds and difficulty of jaw movement were the most common of the TMD signs and symptoms. Open bite, posterior crossbite, and deep bite were the most prevalent types of malocclusion in both groups. Thus, some specific types of malocclusion were significantly associated with the occurrence of TMD. PMID- 8358363 TI - Parasagittal magnetic resonance imaging of the lateral pterygoid muscle: a preliminary study. AB - Ten anatomic territories, including both lateral pterygoid muscle and temporomandibular joint heads, were explored with magnetic resonance imaging in subjects with no dysfunctional disorders. The sequence used was one of inversion recovery, supplemented with image contrast reversal for better visualization. The muscles were observed in the resting position and in dynamic relation. Slice plane definition provided information on the anatomic variations of the superior head and on the muscle-articular junction, in particular on the fascicular aspect of the superior lateral pterygoid muscle and on the differentiation between condyle insertions under effort. The choice of technique and the results are discussed. Avenues are opened for the exploration of muscles utilizing magnetic resonance imaging. PMID- 8358364 TI - Prevalence of oromandibular dysfunction in a general population. AB - The prevalence of oromandibular dysfunction was studied in 735 subjects from a random sample population of 1,000 subjects aged 25 to 64 years. A diagnosis of oromandibular dysfunction was based on criteria established by the International Headache Society, as a subgroup to tension-type headache. Tenderness in pericranial or jaw muscles was not included. The most common symptoms were clenching (22%) and grinding of teeth (15%). The most common sign was irregular jaw movements on opening and closing (29%). The ratio of men to women for most symptoms and signs ranged from 2:3 to 1:3. This study serves as a base in evaluating the importance of oromandibular dysfunction as a causative factor for tension-type headache. PMID- 8358365 TI - Assessment of mandibular function impairment associated with temporomandibular joint osteoarthrosis and internal derangement. AB - Clinical assessment of function impairment associated with temporomandibular disorders should not only comprise diagnostic assessment of symptoms and signs but also function impairment assessment in the patient's value system. Regarding clinical assessment methods, the range of opening movement has been demonstrated to be one of the few variables that can be measured reliably. However, this variable allows no distinction to be made between articular and muscular causes of movement restriction. To assess joint mobility, a combination of indirect and direct assessments is proposed, including the range of opening movement after passive stretch, the range of horizontal excursion toward the opposite side, and the condylar translatory capacity by palpation. In clinical practice, signs and symptoms needed for diagnosis are frequently used as the only basis for mandibular function assessment. Function assessment in the patient's value system, however, is a neglected area in outcome assessment. The main objective of this study was to design and clinimetrically evaluate a mandibular function impairment questionnaire. The relationship between jaw function impairment and measures of pain, movement restriction, and psychological distress was assessed. The questionnaire appears to be a reliable and valuable complementary tool for assessing mandibular function impairment. PMID- 8358366 TI - The degree to which attrition characterizes differentiated patient groups of temporomandibular disorders. AB - Dental attrition severity as the cumulative record of parafunctional and functional wear was graded from study cast analysis using established methodology. Attrition severity was compared in anterior, posterior mediotrusive, and posterior laterotrusive segments. Attrition scores in 48 female and 100 male totally asymptomatic controls were compared to 239 female and 31 male patients differentiated into five patient groups of temporomandibular disorders: (1) disc displacement with reduction, (2) disc displacement without reduction, (3) osteoarthrosis with a history of prior derangement, (4) osteoarthrosis without a history of prior derangement, and (5) myalgia only. All the male patients were in the myalgia-only group. Age was controlled in the analysis to control for functional wear. Comparisons between patients and controls were made according to 10-year age intervals. Analysis included ANCOVA confirmed by a Games-Howell post hoc test, with P < .01 interpreted as a significant difference in the attrition score. Only 1 of 112 ANCOVAs showed a significant difference, with younger men from 20 to 29 years of age in the myalgia-only group having lower mediotrusive attrition than the male controls. It would therefore be difficult if not impossible to differentiate patients from nonpatients based on the severity of dental attrition. Consequently, a major peripheral occlusal etiologic role for attrition in TMD is questioned. Some clinical implications are elaborated. PMID- 8358368 TI - Osteochondroma of the mandibular condyle mimicking TMJ syndrome: clinical and therapeutic appraisal of a case. AB - This paper describes a patient in whom a huge osteochondroma of the mandibular condyle was mistakenly treated as temporomandibular joint syndrome for approximately 6 months before an accurate diagnosis was made. While clinical and pathologic features of this lesion are discussed, further emphasis is placed on the surgical management and immediate reconstruction with autogenous costochondral grafting. PMID- 8358367 TI - The incidence of TMJ dysfunction in patients who have suffered a cervical whiplash injury following a traffic accident. AB - Forty consecutive patients with a cervical whiplash injury were examined and compared with 40 matched controls. The incidence of signs and symptoms was high in both groups. Temporomandibular joint pain (P < .001), limitation of mouth opening (P < .01), and masticatory muscle tenderness (P > .01) were found significantly more frequently in the patient group, while the presence of joint sounds, deviation during mouth opening, and the overall presence of a symptom were not significantly different between groups. When asked whether they would seek treatment for the observed signs and symptoms, a significantly higher number of the whiplash group responded positively when compared to the control group. These findings warrant further study and suggest the benefit of a routine examination of the temporomandibular joint and masticatory system in patients with cervical whiplash injury. PMID- 8358369 TI - Ciguatera fish poisoning--Florida, United States, 1991. PMID- 8358371 TI - The future of implant education: a prediction. PMID- 8358370 TI - An outbreak of severe paralytic shellfish poisoning in British Columbia. PMID- 8358372 TI - Osseous changes following placement of the transmandibular implant system in edentulous mandibles. AB - The transmandibular implant system is designed for the reconstruction and rehabilitation of the endentulous mandible utilizing an extraoral approach. Transmandibular implants were placed in 19 patients and mandibular bony changes were followed using standardized panoramic radiography. Eleven sites were identified on each postoperative radiograph and the percentage of radiographic enlargement was calculated for each site. The true bony changes were then computed for both short-term (9.4 months) and long-term (53.4 months) follow-up. Patients with an average mandibular height in the saddle areas of 3.5 to 8.9 mm showed bilateral bony regeneration in the saddle areas and over the most distal cortical screws of the implants. Most of these bony changes were seen in the first year, but continued beyond that time. Patients with residual bone height of 9.0 to 12.9 mm had little bone change, while patients with bone height of 13.0 to 20.5 mm demonstrated slight resorption. Theories for the observed changes are presented. The transmandibular implant is especially indicated for the severely atrophic mandible because its position within the mandible and the rigid box frame design of the implant promote bilateral bone regeneration distal to the framework of the implant. PMID- 8358373 TI - Chemotherapeutics in implant dentistry. AB - Adjunctive treatment with various chemotherapeutic regimens in implant dentistry are reviewed along with the indications for specific approaches. The use of systemic antibiotics, topical antimicrobials, and various mechanical modalities are discussed in relation to patient maintenance and the repair of ailing implants. PMID- 8358374 TI - The use of free gingival grafts in the treatment of peri-implant soft tissue complications: clinical report. AB - Soft tissue complications including gingival hyperplasia, peri-implantitis, inadequate vestibular depth, and insufficient attached tissue may occur adjacent to endosseous implants. In most clinical cases vestibuloplasty and grafting techniques to establish a wider zone of keratinized tissue are not needed. A clinical case is presented involving peri-implant mucosal areas exhibiting persistent inflammation and progressive recession. A free gingival palatal graft was used to correct the soft tissue defects and provide optimal peri-implant health in order to increase the long-term prognosis of the implant reconstruction. PMID- 8358375 TI - Mechanical tooth concepts in implant dentistry. AB - A brief history of mechanical tooth concepts is presented with an update and discussion of the three basic categories of designs presently available. The application of mechanical designs to implant dentistry is covered with a discussion of indications, contraindications, and technical requirements for each of the categories. PMID- 8358376 TI - The role of a hospital-based dental implant center. AB - The role of a hospital-based implant center with dental and medical specialists working as a team is discussed. Advantages to the team include the availability of sophisticated hospital equipment and facilities. Referring dentists are encouraged to participate in and/or observe treatment performed at the implant center. Four cases treated by an implant team within a hospital environment are presented. PMID- 8358377 TI - The use of demineralized freeze-dried bone and nonresorbable hydroxyapatite in the treatment of buccal dehiscences around implants: clinical reports. AB - A mixture of equal parts of demineralized freeze-dried human cortical bone and nonresorbable porous hydroxyapatite was used in conjunction with expanded polytetrafluoroethylene membrane to promote deposition of bone in buccal dehiscences around dental implants. Two case studies are presented. PMID- 8358378 TI - The edentulous mandible opposing maxillary natural teeth: treatment considerations utilizing implant overdentures. AB - The restoration of the edentulous mandible opposing all or part of the maxillary natural dentition with implant overdentures is described. There are many situations in which the maxillary teeth opposing an edentulous mandible can and should be retained. Mandibular implant overdentures can be utilized as long as health considerations, morphologic features of the resorbed mandible, and maxillomandibular jaw relationships are satisfactory. PMID- 8358379 TI - Providing optimum torque to implant prostheses: a pilot study. AB - Ten N/cm torque has been proposed as the optimum level for the tightening of implant retaining gold screws in order to preload the implant components to limit loosening and fracture. The purpose of this study was to determine the influence of instrumentation and operator experience on the torque generated during manual tightening of slotted gold screws. Sixteen subjects, divided into four groups based on experience, were instructed to tighten five screws into implant analogs with 20-mm and 37-mm slotted screwdrivers. The screws were then removed with a torque gauge. All of the groups of subjects were able to generate significantly greater torque with the 37-mm screwdriver. Dentists with no implant treatment experience generated significantly less torque than the other three groups. Of the 12 dentist subjects, only 3 generated the optimal amount of torque when using the 20-mm screwdriver. Operators who had little experience dealing with implant prostheses were not able to provide the recommended torque and experienced operators tended to generate more than the recommended amount. None of the subjects were able to generate consistent torque values. PMID- 8358381 TI - Separation and characterization of dermatan sulfate in normal human urine. AB - Dermatan sulfate excreted in normal human urine was isolated and characterized by TLC and cellulose acetate strip electrophoresis after cetylpyridinium chloride precipitation and pronase digestion. In these separation methods, dermatan sulfate and chondroitin sulfate were extracted and then monitored by sensitive HPLC methods with post column fluorometric derivatization coupled with chondroitinase ABC, ACII and B digestion. From the results, we demonstrated that human urinary dermatan sulfate contains iduronic acid as its major uronic acid (80-90% of total uronic acid), and is composed mainly of repeated mono-sulfated disaccharide units [Di-4S (structure shown in Fig. 1), 89%] and small numbers of di-sulfated disaccharide units (Di-diSB, 7% and Di-diSE, 1%). PMID- 8358380 TI - Structural diversity of mammalian hepatic dermatan sulfates. AB - Dermatan sulfate-proteoglycans (DS-PGs) were extracted from rabbit, rat and bovine defatted livers by magnesium chloride extraction and DEAE-cellulose chromatography, and then submitted successively to Asahipak GS-520 gel filtration chromatography, Asahipak ES-502N anion exchange chromatography, and cellulose acetate membrane electrophoresis. The disaccharide composition of the glycosaminoglycan chains was determined by differential digestion by chondroitinase ABC, AC, ACII and/or B followed by HPLC for analysis of the resulting unsaturated disaccharides. The hepatic dermatan sulfate chains contained disulfated disaccharide units; Di-diSB and Di-diSE. The hepatic DS-PGs were divided into two groups; Di-diSE-poor DS-PGs and Di-diSE-rich DS-PGs. The iduronic acid content of Di-diSE-poor dermatan sulfate chains was higher than that of Di-diSE-rich ones. PMID- 8358382 TI - Enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae. AB - Squalene epoxidase is a microsomal membrane-associated enzyme that acts as an important regulator in the sterol biosynthetic pathway. In this study, the enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae were examined. Unlike Candida squalene epoxidase, S. cerevisiae squalene epoxidase required NADPH for enzyme reaction. However, S. cerevisiae enzyme reaction did not require FAD or autologous S105 fraction. Unlike rat squalene epoxidase, the activity of S. cerevisiae was reduced by Triton X-100, a nonionic detergent. Terbinafine, an inhibitor of fungal squalene epoxidase, inhibited the enzyme in a non-competitive manner, while NB-598, an inhibitor of mammalian squalene epoxidase, barely inhibited it in a partially non-competitive manner. Thus, the properties of squalene epoxidase from S. cerevisiae were different from those of squalene epoxidase from rats and Candida, which were previously known. We propose that a species difference of squalene epoxidase exists not only between animals and fungi but between Candida and Saccharomyces. PMID- 8358383 TI - Purification and some properties of ribonuclease from Xenopus laevis eggs. AB - A 122 kDa RNase from eggs of Xenopus laevis was purified by sequential chromatography on Sephadex G-75, DEAE-cellulose, heparin-Sepharose and TSK gel G3000SW columns, and gave a single 60 kDa band on SDS-polyacrylamide gel electrophoresis under reducing and nonreducing conditions. The RNase composed of two 60 kDa subunits is able to recognize pyrimidine bases specifically. The pH optimum of the RNase was 7.5 in Tris-HCl buffer. The enzyme activity was abolished by treatment at 80 degrees C for 5 min and pH 2 or 12 for 1 h. Since egg lectins with RNase activity obtained from Rana catesbeiana and R. japonica and bovine pancreatic RNase A show about 30% protein homology and these three proteins are 12-14 kDa heat-stable RNases, [K. Titani, K. Takio, M. Kuwada, K. Nitta, F. Sakakibara, H. Kawauchi, G. Takayanagi and S. Hakomori, Biochemistry, 26, 2189 (1987); Y: Kamiya, F. Oyama, R. Oyama, F. Sakakibara, K. Nitta, H. Kawauchi, Y. Takayanagi and K. Titani, J. Biochem. (Tokyo), 108, 139 (1990)], the data suggest that the X. laevis egg RNase is a unique protein compared with RNases from not only amphibians, but also mammals. PMID- 8358384 TI - Effects of synthetic trypsin inhibitors on the cell cycle of synchronized HeLa cells. AB - HeLa cells were synchronized by a double-thymidine block. After removal of thymidine, the cells immediately caused the uptake of [3H]thymidine into DNA and reached a half-maximum. The duration of the cell cycle was 23 h, and definite changes in cell density were observed between 12 and 13 h and between 35 and 36 h after removal of thymidine. Thus, the initiation time of S phase could be fixed. A trypsin-like proteinase appearing at around 17 h 17 min after removal of thymidine and correlated with the onset of the second S phase, tryptase 17:17 [cf., M. Muramatu et al., Biochim. Biophys. Acta, 1087, 87 (1990)], was obtained. 4-tert-Butylphenyl and 4-biphenyl esters of trans-4 guanidinomethylcyclohexanecarboxylic acid (GMCHA) and amidinopiperidine-4 alkanoic acids, trypsin inhibitors, strongly inhibited the tryptase activity, and these esters exert different effects on the cell cycle of HeLa cells at concentrations showing complete inhibition or maximal inhibitory effect on the tryptase. Both esters of GMCHA elongated the onset of the second S phase for 3 h. Esters of amidinopiperidine-4-acetic and 4-propionic acids showed a similar effect at lower concentrations than GMCHA esters. 4-tert-Butylphenyl esters of amidinopiperidine-4-propionic acid and butyric acids strongly suppressed the second S and M phases by probably affecting the G1 late phase, since they have no effect on the first S and M phases. The addition of amidinopiperidine-4 carboxylic acid 4-tert-butylphenyl ester 0 min after removal of thymidine into the cells completely suppressed the first S and M phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358385 TI - Effects of highly purified ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on rabbit platelets. AB - The effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), highly purified ethyl ester of icosapentaenoic acid (EPA), on rabbit platelets were studied. In in vitro, highly purified EPA (62.5-3000 microM) suppressed the platelet aggregation induced by collagen, arachidonic acid (AA) and adenosine diphosphate (ADP). In ex vivo, a single administration of EPA-E (300 and 1000 mg/kg, p.o.) and repeated administrations (30 and 300 mg/kg/d, p.o.) for 2 weeks showed no effects on collagen-, AA- and ADP-induced platelet aggregation. Repeated administrations (30 and 300 mg/kg/d, p.o.) for 4 weeks suppressed the collagen-induced platelet aggregation, but not the AA- and ADP-induced platelet aggregation. Repeated administrations for 4 weeks also suppressed thromboxane B2 (TXB2) formation induced by collagen, but a single administration and repeated administrations for 2 weeks failed to inhibit TXB2 formation. The EPA level in the platelet phospholipids increased slightly with a single administration, and increased markedly with repeated administrations for 2 and 4 weeks. The AA level in the phospholipids showed practically no changes with a single and repeated administrations. These results suggested that highly purified EPA-E could reduce platelet aggregability by the change of the EPA level in the platelet phospholipids and should allow for a reasonable period of administration. PMID- 8358386 TI - Protective effects of dithiocarbamates against toxicity of cis diamminedichloroplatinum in mice. AB - The protective effects of various dithiocarbamates such as N-benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), and diethyldithiocarbamate (DDTC) on cis-diamminedichloroplatinum (DDP)-induced toxicity in mice were studied. The mice were injected i.v. with a chelating agent (1 mmol/kg) immediately or 5 min after i.v. injection of DDP (15 or 20 mg/kg). The lethal toxicity of DDP (20 mg/kg) was completely prevented by treatment with HBGD or CBGD immediately after DDP. The survival time of mice treated with HBGD or CBGD 5 min after DDP tended to be longer than that treated with BGD or DDTC. Significant increases in blood urea nitrogen (BUN) level and plasma aspartate aminotransferase (AST) activity were observed 3d after DDP injection. The increase in BUN level was completely prevented only by HBGD and CBGD among these chelating agents, while increase in AST activity was significantly prevented by treatment with these two agents. Treatment with HBGD or CBGD immediately after DDP (20 mg/kg) completely protected against DDP-induced diarrhea. These chelating agents significantly decreased the platinum (Pt) contents in the kidney and liver after DDP administration. Treatment with HBGD or CBGD was the most effective in decreasing the renal Pt content, resulting in maximum protection against DDP induced renal damage. The antitumor efficacy of DDP (15 mg/kg) in the colon 26 carcinoma-bearing mice was not affected by HBGD administration. PMID- 8358387 TI - Effect of preinduction of metallothionein on tissue distribution of silver and hepatic lipid peroxidation. AB - Silver ion causes a number of toxic effects, it decreases the activities of lactate dehydrogenase and glutathione peroxidase, and the peroxidation of membrane lipids. Silver ions complex strongly to sulfhydryl groups and the effects of preinduction of metallothionein, a sulfur-rich protein, on silver administration in rats were examined. The preinduction of metallothionein decreased the mortality of mice following silver administration. A major portion of the incorporated silver in the liver was bound to the basal membrane and cellular components, and the distribution of silver into cytosol was small. The preinduction of metallothionein decreased the amount of bound silver in the membrane and increased the distribution of silver in the cytosol; in addition, it depressed silver-induced lipid peroxidation in liver. PMID- 8358388 TI - Absorption mechanism of 1,3-bis(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy )propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate. AB - To clarify the absorption mechanism of 1,3-bis(2-ethoxycarbonylchromon-5-yloxy)-2 ((S)-lysyloxy+ ++)propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate (DSCG), a study was made using rats. N-556 gave the highest plasma level of DSCG following its injection into the loop at the upper part of the small intestine. N-556 was stable in acidic washings of gastric contents, but rapidly hydrolyzed to M1 with twin ethyl residues on DSCG in the washings of the small intestinal contents. N-556 and M1 were hydrolyzed to DSCG via M2 having a mono ethyl residue in the homogenate of the small intestinal mucosa. The oral absorption of M1 following its administration in 50% (v/v) propylene glycol solution was essentially the same as that of N-556. That of M1 administered in aqueous suspension was low. After the oral administration of N 556, a small amount of M2 and a trace of M3 having L-lysyl residue were detected in the portal plasma, but no hydrolytic intermediate except DSCG could be found in the general plasma. The major absorption mechanism of N-556 may thus be concluded as follows: N-556 given orally is transferred to the small intestine in essentially intact form. N-556 is then rapidly diffused to an aqueous layer on the surface of the mucosal membrane and hydrolyzed to M1. The resultant M1 is transported to the mucosal membrane and hydrolyzed to DSCG via M2. DSCG generated in the mucosal membrane is used for general circulation through the portal blood and liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358389 TI - Antitumor activities of ellagitannins against sarcoma-180 in mice. AB - Forty-five ellagitannins and related compounds were intraperitoneally injected into mice once, 4 d before intraperitoneal inoculation of S-180 cells, and their antitumor activities were evaluated. When an antitumor-active tannin was defined as one producing a 70% increase or more in the mean life span of mice or one regressor out of six mice, twenty-one ellagitannins were active. Among monomeric ellagitannins, tellimagrandin II was most active. Most of the oligomeric ellagitannins, consisting of tellimagrandins I and II as the monomer unit, had a significant antitumor activity. Macrocyclic ellagitannins were all active. Oenothein B, among them, had the most potent antitumor activity. In contrast, ellagitannins containing a casuarictin or potentillin moiety in their molecules, except for extensively oligomerized ones, showed very low or negligible activity. These results suggest that tannins need the ellagitannin monomer units, having galloyl groups at the O-2 and O-3 positions on the glucose core(s), such as tellimagrandins, in order to exhibit a strong antitumor activity. PMID- 8358390 TI - p-Aminohippurate transport in rat renal brush-border membranes: a potential sensitive transport system and an anion exchanger. AB - Transport mechanisms of p-aminohippurate (PAH) were investigated in rat renal brush-border membrane vesicles. The uptake of PAH was stimulated by an inside positive membrane potential created by K+ and valinomycin. This potential stimulated uptake of PAH was inhibited by various anion transport inhibitors and was saturable. In addition, PAH uptake in the presence of valinomycin was linearly increased in proportion to log[K+]out/[K+]in. On one hand, PAH uptake was stimulated by [14C]PAH/PAH or [14C]PAH/Cl- exchange, and the [14C]PAH/PAH exchange was insensitive to the membrane potential. The uptake by the exchanger was also inhibited by anion transport inhibitors, but the potential-stimulated uptake of PAH was more sensitive to furosemide and 4,4'-diisothiocyano-2,2' disulfonic stilbene. On the contrary, [14C]PAH/PAH exchange was more sensitive to urate than the potential-stimulated uptake of PAH. These findings indicate that PAH is transported by two distinct transport systems in rat renal brush-border membranes, a potential-sensitive transport system and an anion exchanger. PMID- 8358391 TI - Freeze-drying of cephalothin sodium: granularly agglomerated crystallization during freezing. I. AB - Optimal conditions for the crystallization and subsequent freeze-drying of an aqueous cephalothin sodium (CET-Na) solution of supersaturated concentrations to obtain granular crystalline CET-Na have been discussed, as have the qualities of the product thus obtained. In general, CET-Na in supersaturated aqueous solution is barely recrystallized, even when in its frozen stage. Our previous report revealed that when the solution is kept at low temperatures for a long duration, the molecules begin to change structurally to as condensed a state as that of liquid crystals, and such change facilitates a spontaneous nucleation and seed independent crystal growth in the frozen solution. These findings prompted the authors to investigate optimal CET-Na concentrations and thermal histories during the crystallization and subsequent freeze-drying process without seeding. It has subsequently been found out that optimization of the latter conditions gives granular agglomerated crystalline CET-Na contaminated with neither the amorphous nor the quasi-crystalline form. The optimized conditions are: 25-28% CET-Na concentrations; storage before the freezing process at 0 degrees C for 2 h, and subsequent storage at 20-25 degrees C for 1 h; cooling in the freezing process at a rate not faster than 0.5 degrees C/min; warming of the solution for facilitating crystallization prior to vacuum application for drying at -4 degrees C. Under these conditions, the freeze-dried product of CET-Na in granular form has been successfully obtained in a shorter freeze-drying cycle, exhibiting a faster reconstitution time than those of CET-Na prepared according to seeded crystallization followed by a conventional freeze-drying. PMID- 8358392 TI - Freeze-drying of cephalothin sodium: granularly agglomerated crystallization during freezing. II. AB - The mechanism of granularly agglomerated crystallization during freezing of cephalothin sodium (CET-Na) in aqueous solution has been discussed. Our previous report noted that strict control of the following is important in order to obtain crystalline granular agglomerates of CET-Na: (1) thermal history of the solution before receiving freezing, (2) cooling rate in freezing, and (3) aging temperature level in the crystal growth step. In order to clarify the physico/chemical meanings of the individual controls, further investigations have been made: 1) with varying thermal history, aqueous 30-% CET-Na solutions were prepared for storage, first at 0 degrees C with its supersaturation and secondly at 25 degrees C, in an unsaturated state for observing any structural changes by viscosimetry, refractometry, and surface tensiometry; 2) morphological changes in ice crystals during freezing at varying cooling rates, as well as those during the crystal growth step, were observed by polarized-light cryomicroscopy and scanning electron microscopy; 3) melting, as well as crystal growth, at several aging temperature levels were observed by electrical conductometry and also by the above-mentioned techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358393 TI - Immunopharmacological characterization of a highly branched fungal (1-->3)-beta-D glucan, OL-2, isolated from Omphalia lapidescens. AB - The immunopharmacological activities of a fungal (1-->3)-beta-D-glucan, OL-2, isolated from "Leiwan" Omphalia lapidescens were examined. Intraperitoneal (i.p.) administration of OL-2 to ICR mice induced a significant number of peritoneal exudate cells (PEC) and white blood cells over the period of a few days. Spleen cell numbers were also increased by i.p. administration of OL-2 at about a week. These changes reverted to the normal level within a month. Responses of spleen cells and bone marrow cells (BM) to colony stimulating factors (CSF) were augmented by OL-2 administration assessed by cell proliferation assay. Sera from OL-2 administered mice contained an increased concentration of colony stimulating activity. Gene expressions of interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha in the spleen were also increased. These results suggested the activation of hematopoietic responses, and would well relate to the incremental increase in PEC, white blood cell and spleen cell numbers. OL-2 also increased the serum concentration of fibronectin and complement component C-3. However, OL-2 did not show adjuvant activity to SRBC and antitumor activity against the solid form of Sarcoma 180 by i.p. administration. Yet, OL-2 did not interfere with the antitumor activity of SSG against the same tumor system. These facts suggested that OL-2 could enhance nonspecific host defense mechanisms by enhancing hematopoietic responses, but would not enhance or inhibit the specific immunity mediated by lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358394 TI - Preparation and evaluation of a controlled-release formulation of nifedipine using alginate gel beads. AB - Alginate gel beads containing nifedipine (NP) were prepared using a gelation of alginate with calcium cations. The dissolution and absorption of NP from alginate gel beads were evaluated as a controlled-release formulation of NP. The release of NP from alginate gel beads was affected by the composition of uronic acid in alginate, and by the NP content in alginate gel beads. NP absorption after oral administration to beagle dogs of alginate gel beads prepared by air-drying was significantly lower than that after the administration of NP powder alone, due to the limited release of NP from the alginate gel beads in the gastrointestinal tract. On the other hand, the alginate gel beads prepared by freeze-drying improved the absorption of NP because of the increasing disintegration of alginate gel beads with decreasing structural strength. However, this method had poor reproducibility, compared with air-dried alginate gel beads. The gel beads with added alginate propylene glycol ester (PGA) swelled and released calcium ions rapidly, even in water. This is because PGA gels weakly to the calcium cation. Consequently, it was observed that NP release from the PGA gel beads was highly accelerated compared to the release from alginate gel beads. The higher serum level of NP with large variance was obtained after the oral administration of the PGA gel beads. Gel beads consisting of a 1:1 ratio of PGA to alginate had intermediate characteristics between the alginate and PGA gel beads in respect to NP release and absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358395 TI - Influence of lacquer thinner and some organic solvents on reproductive and accessory reproductive organs in the male rat. AB - The effects of thinner and its main components, toluene, xylene, methanol, and ethyl acetate, on reproductive and accessory reproductive organs in male rats were studied. The vapour from these organic solvents was inhaled twice a day for 7 d. Following inhalation of thinner vapour for 7 d, the weights of the testes and prostate fell and acid phosphatase activity in the prostate and plasma testosterone levels were significantly decreased compared with the control group. Both ethyl acetate and xylene caused a decrease in the weight of the testes and accessory reproductive organs, as well as reducing acid phosphatase activity in the prostate and plasma testosterone levels. In contrast, toluene and methanol had no effect on organ weights, circulating testosterone levels, or on enzyme activity. Body weight was decreased by inhalation of thinner or ethyl acetate vapour. Spermatozoa levels in the epididymis were decreased by inhalation of ethyl acetate and xylene vapour. These results suggest that thinner, particularly the components ethyl acetate and xylene, interfere with the functions of the testes and accessory reproductive organ; toluene has no effect on these functions. PMID- 8358396 TI - Cardiac glycoside-induced elevation of intracellular Na+ ion concentration in human erythrocytes studied by 23Na NMR spectroscopy: relationship between inotropy speed and elevation rate of intracellular Na+ ion concentration. AB - Elevation of intracellular sodium ion concentration in human erythrocyte induced by the cardiac glycoside, proscillaridin, and its four derivatives was measured using 23Na NMR spectrometry. In this examination, there was a significant correlation between the time to half maximum inotropic effect and the time to maximum of Na+ concentrations in human erythrocyte, determined by 23Na NMR. PMID- 8358397 TI - Lignified materials as medicinal resources. VI. Anti-HIV activity of dehydrogenation polymer of p-coumaric acid, a synthetic lignin, in a quasi-in vivo assay system as an intermediary step to clinical trials. AB - After the dehydrogenation polymer of p-coumaric acid, a synthetic lignin, was intravenously injected into mice, the serum was collected immediately, 15 min, 1 h, 5 h, and 24 h after the injection. The serum thus obtained was added to the assay medium containing MT-4 cells infected with HTLV-IIIB (an HIV-1 strain). Inhibition of the cytopathogenicity of HIV by these serum preparations was assayed by the MTT method. The result revealed that lignins could be a promising class of anti-HIV agents with an unidentified unique mode of action. PMID- 8358398 TI - An efficient radiosynthesis of [18F]fluoromisonidazole. AB - An efficient preparation of the hypoxic cell tracer [18F]3-fluoro-1-(2'-nitro-1' imidazolyl)-2-propanol ([18F]fluoromisonidazole) is reported. This radiopharmaceutical is of interest to probe hypoxic tissue in infarcts and tumors. One-step radiolabeling and rapid protection group removal provided 55-80% yield in 50 min. The process is similar to common fluorine labeling procedures, simplifying the procedure for most laboratories, and offers an improvement over more difficult previous methods. The labeling precursor was prepared in five steps from readily available materials in a straightforward reaction scheme. PMID- 8358399 TI - Determination of 90Sr in milk by using two inorganic exchangers. AB - Two inorganic exchangers, consisting of PRTD (partially reduced tin dioxide) and CUCR (normal copper chromate), both prepared and studied by the authors, were investigated for radiochemical isolation and purification of 90Sr from milk samples. A procedure combining the use of both exchangers is reported and is recommended when it is necessary to remove a radiobarium interference. Due to the lack of appropriate samples the procedure was tested using defatted milk spiked with 90Sr and 133Ba. PMID- 8358400 TI - The use of cotton balls to collect infant urine samples for 2H/1H and 18O/16O isotope ratio measurements. AB - To test the validity of cotton balls as a urine collection medium for hydrogen and oxygen isotope ratio measurements, we moistened cotton balls with 1-, 5-, and 10-mL aliquots of urine that contained either natural abundances or one of two enriched levels of 2H and 18O. The liquids were then expressed from the cotton balls, either at once, or after 30 or 60 min of atmospheric exposure, and analyzed for their 2H/1H and 18O/16O isotope ratios. The 2H abundances of the fluids expressed from the cotton balls were significantly lower than the original values. This dilution of 2H, however, diminished in the samples that had a greater volume of urine. We observed no effects of volume or time on 18O. Our results indicate that at low urine volumes, ambient moisture dilutes 2H in the cotton balls, but isotope exchanges and evaporation have little or no effect on the hydrogen and oxygen isotopic abundances of the urine samples. Total body water and energy expenditure values calculated from the 2H and 18O enrichments of 5- and 10-mL urine samples were within 1% of the theoretical values. Therefore, cotton balls are suitable for collection of infant urine samples for hydrogen and oxygen isotope ratio measurements, if the volume of urine that can be expressed from a cotton ball is > or = 5 mL. PMID- 8358401 TI - Application of microwave heating to the synthesis of [18F]fluoromisonidazole. AB - A modified synthesis of [18F]fluoromisonidazole is reported which makes use of microwave heating to reduce the synthesis time to ca 70 min from EOB. A remote system for column purification, concentration and delivery to an HPLC syringe, which reduces the total absorbed dose to the operator, is also described. PMID- 8358403 TI - Abnormal patterns of speech breathing in dysarthric speakers following severe closed head injury. AB - The respiratory abilities of a group of 20 subjects with a speech disorder resulting from severe closed head injury (CHI) were assessed using both spirometric and kinematic techniques and compared with those of a group of 20 non neurologically impaired controls matched for age and gender. Results of the spirometric assessment showed that the CHI subjects as a group had lower vital capacities and lower forced expiratory volumes 1 second than the controls. Kinematic assessment also showed that the CHI subjects had problems co-ordinating the action of the rib-cage and abdomen when carrying out speech tasks such as vowel prolongations, syllable repetitions and reading. Results are discussed in terms of the effects of CHI on neuromuscular function. PMID- 8358402 TI - Statistical profile of traumatic brain injury: a Canadian rehabilitation population. AB - A retrospective clinical hospital chart study was undertaken to prepare a statistical profile of traumatic brain-injured patients in rehabilitation. It included 498 consecutive admissions to the Traumatic Brain Injury Rehabilitation Program of the Queen Elizabeth Hospital (Toronto, Canada) from 1978 to 1991. Descriptive statistics were obtained for age, gender, marital status, educational status, occupational status, history of drug and alcohol use, cause of injury, month of injury and length of coma. Comparisons are made between the studied population and several Canadian centres, as well as international brain injury demographics in the literature. Results are discussed in terms of the gender differences and lifestyle parameters associated with brain injury. PMID- 8358404 TI - Glasgow Outcome Scale: an inter-rater reliability study. AB - This study was set up to test the reliability of the Glasgow Outcome Scale (GOS) when information was obtained from different sources. Eighty assessments were carried out on a group of 58 patients at three different time intervals up to 24 months post-injury. Each assessment consisted of three independently obtained GOS scores for each patient; (i) a score by a research psychologist after interview and neuropsychological testing of the patient; (ii) a score, obtained by post, by the patient's general practitioner (GP), and (iii) a score made by a research worker based on questionnaire information obtained from relatives by post. The agreement between the psychologist's score and that based on the relatives' information was high (r = 0.79 p = 0.001) whereas the correlation between the psychologist's score and that of the GP was low (r = 0.49 p = 0.001). The GPs tended to make overoptimistic assessments and this was most notable at 6 months post-injury when only 50% of the GPs' assessments agreed with those of the psychologist. We have shown that reliability of the GOS varies with the method of obtaining data. Ideally patients should be interviewed and tested by staff who have not been involved in the acute care of the patient. Failing this, information should be obtained from relatives of the patient and used by staff, trained in the use of the GOS, to assign a GOS score. PMID- 8358405 TI - A survey of accredited and other rehabilitation facilities: education, training and cognitive rehabilitation in brain-injury programmes. AB - Although it is routinely acknowledged that cognitive rehabilitation therapy comprises a major part of the services provided to survivors of brain injury, there continues to be no general consensus regarding the methods and training of those who provide cognitive rehabilitation services. This survey of 398 head injury rehabilitation facilities includes information on which disciplines are providing and supervising cognitive rehabilitation therapy, which therapy formats are used, and a first attempt to define the costs and providers for cognitive therapy staff training in Commission on Accreditation of Rehabilitation Facilities (CARF) approved and other (non-CARF) facilities. The education and training of junior and senior staff members is compared, and respondents suggest changes in the education and training of those who provide cognitive rehabilitation therapy. The results of this survey suggest no significant differences in the organization and delivery of cognitive rehabilitation therapy in CARF and non-CARF programmes. They indicate that cognitive rehabilitation therapy and the education and training of providers deserve further study and definition, given the widespread provision of cognitive rehabilitative services. PMID- 8358406 TI - A double-blind controlled study of methylphenidate treatment in closed head injury. AB - Closed head injuries (CHI) may produce permanent, disabling changes in cognitive functions and social behaviour. Recent clinical case reports have suggested that stimulant medications may improve neurobehavioural functioning in CHI patients. In the present study, we evaluated the effects of methylphenidate (0.3 mg/kg b.i.d.) in 12 chronic CHI patients (14 to 108 months post-injury) using a double blind, placebo-controlled, randomized, crossover design. Outcome measures consisted of cognitive tests of attention, learning and cognitive processing speed. In addition, a rating scale was completed by a close friend or relative to assess social behaviour. No significant differences were found between drug and placebo conditions on any of the neurobehavioural measures. These data do not support the clinical use of methylphenidate in the treatment of CHI patients. PMID- 8358407 TI - Oral hygiene following traumatic brain injury: a programme to promote dental health. AB - Dental care and oral hygiene programmes for persons with traumatic brain injury (TBI) have been relatively ignored areas of clinical care and research. Data regarding the need for structured oral hygiene programmes with this population are sorely lacking. Further, evidence to support or contraindicate the efficacy of such interventions is negligible. The purpose of the present study was to address the need for ongoing dental follow-up and oral hygiene programmes in the post-acute phase of rehabilitation care. A group of 20 TBI patients (10 experimental, 10 control) who were at least 1 month post-injury and had Rancho Los Amigos Scale scores of 6 or greater, were randomly selected for participation in the study. Oral hygiene status was assessed by a dental hygienist using a plaque index score developed by Silness and Loe. The experimental group received individualized oral hygiene instruction along with dental supplies for their personal use, including a dental mirror and red disclosing tablets. The control group received no such instructions or supplies. At 5-6 weeks following initial evaluation, 18 patients (nine from each group) were reassessed via the plaque index score. Comparisons between the control and experimental groups revealed significant differences on follow-up plaque scores with a lower mean score for the experimental group only on baseline and follow-up data yielding a significant decrease in plaque scores over time. These results suggest that dental hygiene interventions for patients following TBI can effectively promote dental plaque control. PMID- 8358408 TI - Hyponatremia-associated cognitive impairment in traumatic brain injury. AB - The case of a traumatic brain injury (TBI) patient with dramatic cognitive deterioration in the absence of medical aetiology other than simultaneous decline in serum sodium led to an investigation of the association between declines in sodium levels and cognitive status. In a population of 50 persons undergoing TBI rehabilitation, 12 (24%) had relative (3 mEq/L) decreases in serum sodium while five (10%) experienced absolute hyponatremia (136 mEq/L). Correlation with cognitive status was significant when the absolute hyponatremia group was compared with those whose sodium levels remained above 136 mEq/L. A case-matched study of the relative hyponatremia group yielded no significant association between sodium-level decreases and cognitive status. These data support previous conclusions indicating wide variation in individual responses to changes in serum sodium. The threshold for significant effects of hyponatremia may be higher in patients with TBI than in populations studied previously. PMID- 8358409 TI - Protriptyline as an alternative stimulant medication in patients with brain injury: a series of case reports. AB - The results of a series of eight individual case reports in which protriptyline, an activating tricyclic antidepressant, was used as a 'stimulant' medication are presented. For some patients with head injury, traditional stimulants, such as methylphenidate, or dopaminergic stimulants, such as levodopa-carbidopa, amantadine, or bromocriptine, may be partially or totally ineffective or not tolerated. Protriptyline can be a very effective alternative and, for some patients, may be the most effective stimulant tried. In low to moderate doses, protriptyline should be considered for trials as an activating/stimulant medication in patients with head injury. PMID- 8358410 TI - Post-traumatic haemorrhage in corpus callosum: a case study of disconnection syndrome. AB - This paper reports the case of a 16-year-old man who had sustained a traumatic head injury. Neuroradiological examinations showed haemorrhagic lesion in corpus callosum. The patient initially demonstrated several symptoms of disconnection syndrome; however, these clinical signs later resolved in subtle dysfunctions that could be evidenced only by statistical analyses of performances to specific tests. It is thus suggested that comparable cases may be undetected by standard examination procedures. PMID- 8358411 TI - Repatriation Community Programs, Part I: A collaborative model of service delivery. AB - The Repatriation Community Programs pilot project was funded by the Ontario Ministry of Health in 1990. Its mandate is to facilitate the return of brain injured individuals from US rehabilitation facilities to their home communities in Ontario. Most Ontario residents receiving rehabilitation in the US fall into one of two 'hard to serve' groups: (1) those with severe behavioural difficulties; and (2) those at various levels of post-comatose unawareness whose families are unwilling to accept chronic care 'maintenance'. The pilot programme has been charged with demonstrating the feasibility of community-based care for severely brain-injured individuals and their families, as well as developing a model of service delivery and interagency collaboration which will expedite province-wide implementation of similar programmes. This paper describes the collaborative model developed over the first 2 years of the project. Issues leading to this model are identified and elements of the model are discussed. PMID- 8358412 TI - Extracorporeal shock wave lithotripsy in patient with cardiac pacemaker in an abdominal location: case report and review of the literature. AB - A 75-year-old man with complete heart block and a ventricular demand pacemaker with the generator in a left upper-quadrant subcutaneous pouch underwent extracorporeal shock wave lithotripsy (SWL) for a 2-cm proximal right ureteral calculus, receiving 2000 shocks at 24 kV. There was no damage or malfunction of the pacemaker, and the Dornier HM3 lithotripter had no difficulty sensing all paced ventricular complexes. The patient had excellent fragmentation of his calculus. Extracorporeal shock wave lithotripsy may be performed safely on patients with pacemakers directly in the path of the shock waves at maximal kilovoltage when appropriate peri-SWL guidelines are followed. Specifically, the treatment should be approved by a cardiologist knowledgeable about the patient and the pacemaker, and a cardiologist should be nearby with the equipment necessary to deal with any problems. Dual-chamber pacemakers should be reprogrammed to the single-chamber mode, and single-chamber rate-responsive devices should have the activity mode programmed off. Patients with the latter type of pacemaker implanted in the abdomen should not have SWL if the device will be close to F2. PMID- 8358413 TI - Absence of activation of proteolytic enzymes by extracorporeal shock waves. AB - The mechanism of tissue damage by extracorporeal shock wave lithotripsy has not been clarified, but proteolytic enzymes are known to play an important role in tissue breakdown in response to other types of injury. Screening tests for activation of the proteolytic enzymes kallikrein, plasmin, trypsins 1 and 2, and granulocyte elastase therefore were performed for 4 to 5 hours in 14 dogs after unilateral treatment with 1500 or 2000 extracorporeal shock waves under anesthesia and vigorous hydration. We also studied the activity of the proenzymes prekallikrein, plasminogen, and prothrombin and three plasma protease inhibitors (kallikrein inhibitor, antiplasmin, and antithrombin III). Blood from both renal veins (treated and control kidneys) and the aorta and tissue samples of the injured renal parenchyma and corresponding areas of the control kidneys revealed no proteolytic enzyme activation by the shock waves and no decline in the activities of proenzymes and enzymes inhibitors. Significant proteolysis does not seem to play a part in the tissue injury induced by extracorporeal shock wave lithotripsy. PMID- 8358414 TI - Compliance with use of the Hydrate 1 system by patients with treated urolithiasis. AB - Adequate hydration, leading to decreased urine osmolality and increased solubility of urinary constituents, is the cornerstone of urolithiasis prevention. Hydrate 1 is a system designed to allow patients to monitor urine osmolality by a simple colorimetric method, thereby adjusting their fluid intake. In 10 patients treated surgically for stone disease, the device worked well when used, guiding patients to increase intake appropriately. However, compliance was sporadic, determined principally by occupational or lifestyle constraints. Use of this system may have a place in that subset of patients with recurrent stone disease who have difficulty maintaining adequate urine volume. PMID- 8358415 TI - Lasertripsy of ureteral calculi using pulsed-dye laser with automatic shut-off after tissue contact. AB - Since June 1991, 54 patients with ureteral calculi (13 upper, 18 middle, and 23 distal) have been treated in our department using a flashlamp-pumped tunable-dye (rhodamine 6G) laser with a wavelength of 594 nm with an energy at the distal fiber tip between 30 and 120 mJ. The fiber core diameters were 200 and 300 microns. By spectral analysis of the reflected light, immediate shut-off of the laser was obtained after tissue contact. In average, 1599 impulses at a mean energy of 76.4 mJ were applied. In 32 cases (59%), complete disintegration was achieved. In 22 cases (41%), partial disintegration was noted, leading to retrograde mobilization of the fragments followed by SWL in 16 patients. Ureteroscopic extraction of fragments was performed in six patients. All patients were rendered stone free after 6 weeks. Because of the ureteroscopic manipulation, mucosal lesions were found in five patients, but no trauma attributable to the action of the laser was seen. In 42 patients, a double-J stent was placed after the procedure. Lasertripsy using a pulsed-dye laser with automatic shut-off after tissue contact is a safe and effective approach that offers a new aspect in the noninvasive treatment of recalcitrant ureteral calculi in our department. PMID- 8358416 TI - Outcomes of non-self-expandable metal prostheses in strictured human ureter: suggestions for future developments. AB - The success of metal stents in the urethra led us to implant flexible metal stents unilaterally in the ureter in four patients. Radiographic and endoscopic controls during follow-up showed an obstruction in three cases. We describe the different aspects of these unfavorable outcomes and propose changes to be made in metal stents for use in the upper urinary tract. PMID- 8358417 TI - Effect of balloon dilation of ureter on upper tract dynamics and ureteral wall morphology. AB - Sixteen male Yucatan minipigs underwent balloon dilation of the right ureterovesical junction (UVJ) and lower ureter to twice its normal caliber. With the bladder open, bilateral upper tract dynamics measurements under different perfusion rates (0.5, 2, and 4 ml/min) were recorded predilation, immediately after dilation, and 1, 2, 3, 4, and 6 weeks after dilation. Immediate and late antegrade nephrostograms, suprapubic cystograms, and right antegrade nephrostograms (oblique view) were taken. In the chronic experiment, no difference in renal pelvic pressure (Ppvs) was detectable between the control and dilated sides immediately after dilation. Only at 4 ml/min was there a statistically significant increase in the Ppvs of the dilated ureter 1 week after dilation when compared with the controls. At 2 weeks, this obstructive change had disappeared. At 3, 4, and 6 weeks, Ppvs of the dilated ureter declined progressively in comparison with the control side, but the difference was not statistically significant. At 6 weeks, Ppvs of the dilated ureter decreased significantly compared with predilation readings only at 4 ml/min. Immediate antegrade radiologic evaluation revealed that 69% of the experimental animals had no extravasation, while 31% showed variable degrees of extravasation, which disappeared completely on late antegrade nephrostograms (6 weeks). Grade 2 reflux occurred in 33% of the experimental animals at 1 week and had disappeared at 6 weeks. Histologic examinations at 1, 2, and 3 weeks revealed a nonhomogeneous pattern of ureteral damage, ranging from total rupture to much less dramatic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358418 TI - Intrarenal access with the flexible ureteropyeloscope: effects of active and passive tip deflection. AB - In flexible ureteroscopy, active deflection of the tip of the endoscope is essential to reach the lateral and inferior infundibula. Two other features may affect endoscope function: one- or two-way deflection and the presence of a secondary, passively deflectable, segment. In our 7-year experience with five different endoscopes, attempts to examine the intrarenal collecting system were successful in 205 of 225 patients (92%). The success rate was lowest with a prototype endoscope, which did not have a secondary deflecting segment. There was no significant difference between those instruments with single- or two-way deflection that possessed secondary deflection. Endoscopes with secondary deflection were most successful in entering the lower pole, and this feature was necessary to reach the entire collecting system in 51% of the patients. Most of the failures of access were in attempts to reach the lower infundibulum. There was some trend toward greater success with the smaller instruments (8.5F). PMID- 8358419 TI - Endoscopic repair of the completely disrupted urethra. AB - Posterior urethral disruption or obliteration is most often the result of pelvic trauma. We describe a modified endoscopic technique used to reestablish urethral continuity in five patients with a minimum 2-year follow-up. This technique involved cold-knife incision of the scar without dilation followed by short-term catheterization. The advantages of endoscopic reestablishment of urethral continuity include short hospitalization, limited blood loss, no external incision, briefer operating time compared with open urethroplasty, and a stable patent urethra. PMID- 8358420 TI - Extraperitoneal endosurgical lymphadenectomy with insufflation in the staging of bladder and prostate cancer. AB - A new technique of endosurgical pelvic lymph node dissection was performed for the staging of 10 prostate and 8 bladder cancers. The technique, involving an exclusive extraperitoneal space development with CO2 insufflation, is described in detail. Using the standard endosurgical (laparoscopic) equipment, we performed a complete bilateral ilio-obturator lymph node dissection in 15 patients (83%). In the remaining three patients, because of technical difficulties, only unilateral dissection was performed. The average operating time was 84 minutes. Morbidity was low (one instance of sepsis). Prospective assessment of CO2 homeostasis showed that arterial CO2 pressure (PaCO2) increased significantly but could be controlled by increasing minute ventilation output. Our results show that perioperative assessment of end-tidal CO2 partial pressure is necessary and sufficient for the adaptation of minute ventilation output. Two patients with prostate cancer had positive nodes. No intraoperative or postoperative morbidity related to the procedure was observed in patients submitted to radical surgery. Extraperitoneal endosurgical pelvic lymphadenectomy with CO2 insufflation is a rapid, safe, and effective method in the staging of urologic pelvic malignancies and represents an alternative to traditional open surgery as well as to conventional transperitoneal laparoscopic lymphadenectomy. PMID- 8358421 TI - Inhibition of peritoneal tumor-cell implantation: model for laparoscopic cancer surgery. AB - A serious concern in applying laparoscopic surgery to malignancies is the possibility of tumor spillage and seeding. We developed a model of peritoneal tumor implantation using a murine bladder tumor cell line, MBT-2. Anesthetized C3H male mice underwent mock laparoscopy with or without peritoneal disruption and instillation of tumor cells via a 16-gauge angiocatheter, and the effect of heparin and the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) on tumor cell adherence and growth was evaluated. Animals were divided into six groups: Group 1 = tumor cells only; Group 2 = peritoneal disruption + tumor cells; Group 3 = heparin + tumor cells; Group 4 = peritoneal disruption + heparin + tumor cells; Group 5 = GRGDS + tumor cells; and Group 6 = peritoneal disruption + GRGDS + tumor cells. In all animals, a greater tumor burden was noted at the sites of peritoneal disruption. Moreover, 50% and 63% of animals in Groups 1 and 2 developed tumors compared with 17% and 31% of those in Groups 3 and 4, respectively. There was significantly more tumor at the sites of peritoneal disruption in the "tumor only" groups than in those that received heparin (mean tumor volume 32.32 mm3 in Group 2 v 2.77 mm3 in Group 4; p < 0.05). The GRGDS-treated groups showed a trend toward decreased number and size of tumors compared with the tumor only groups, although the differences were not statistically significant. These findings imply that prophylactic irrigation with substances that decrease cell adherence may prevent tumor implantation after accidental intraoperative tumor spillage. PMID- 8358422 TI - Laparoscopic retroperitoneal lymphadenectomy in the pig: initial report. AB - The value of retroperitoneal lymphadenectomy in the management of nonseminomatous testicular tumors is still a matter of controversy. Lymphadenectomy doubtlessly has great advantages but is somewhat down-graded by the considerable associated morbidity. Our experimental study in six pigs has shown that retroperitoneal lymphadenectomy by means of laparoscopic techniques is feasible. Clinical trials will follow. Should they prove successful, the role of retroperitoneal lymphadenectomy in the management of testicular tumors has to be reassessed. PMID- 8358423 TI - Prostatic tissue destruction by high-intensity focused ultrasound: experimentation on canine prostate. AB - High-intensity focused ultrasound (HIFU) has been used transrectally to induce intraprostatic coagulation necrosis lesion in the canine prostate. The device combines a firing system (power amplifier and therapy transducer) and a localization system (ultrasound scanner). Thirty-seven dogs have been treated with ultrasound intensity ranging from 720 W/cm2 to 2300 W/cm2 and shot durations ranging from 1 to 4 seconds. The threshold for focal ultrasonic lesions was determined to be 1000 W/cm2 with a 1-second shot duration. Intraprostatic lesions were obtained without any damage to the rectal wall. These lesions were homogeneous coagulation necroses and progressed first to an inflammatory fibrosis and then to sclerosis with cavity formation. Intraprostatic lesions also occurred with a combination of moderate acoustic intensity (720 W/cm2) and longer shot duration (4 seconds). The temperature reached at the focal point of the transducer was 85 degrees C. The study confirms the possibility of creating irreversible lesions in the prostatic tissue through the rectal wall. The destruction of localized prostatic cancer seems to be possible in the near future using HIFU delivered by the transrectal route. PMID- 8358424 TI - Diagnosing the heart of the problem. PMID- 8358425 TI - Are linkage studies boring? PMID- 8358426 TI - Therapies that make sense. PMID- 8358427 TI - No linkage to chromosome 14 in Swedish Alzheimer's disease families. PMID- 8358428 TI - Nonsense mutations and diminished mRNA levels. PMID- 8358429 TI - Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. AB - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder characterized by neurodegeneration of the cerebellum, spinal cord and brainstem. A 1.2-Megabase stretch of DNA from the short arm of chromosome 6 containing the SCA1 locus was isolated in a yeast artificial chromosome contig and subcloned into cosmids. A highly polymorphic CAG repeat was identified in this region and was found to be unstable and expanded in individuals with SCA1. There is a direct correlation between the size of the (CAG)n repeat expansion and the age-of-onset of SCA1, with larger alleles occurring in juvenile cases. We also show that the repeat is present in a 10 kilobase mRNA transcript. SCA1 is therefore the fifth genetic disorder to display a mutational mechanism involving an unstable trinucleotide repeat. PMID- 8358430 TI - Effect of the myotonic dystrophy (DM) mutation on mRNA levels of the DM gene. AB - Myotonic dystrophy (DM) results from the amplification of an unstable CTG repeat in the 3' untranslated region of a transcript encoding a putative serine/threonine kinase. We have analysed the amplification of the repeat and the steady state levels of the DM kinase (DMK) mRNA in tissues and cell lines from normal and congenital DM individuals. Southern blot analysis of DNA samples from a severely affected neonate shows somatic heterogeneity of the repeat in all tissues studied. RNA analyses on these tissues show a marked increase in DMK steady state mRNA levels. We demonstrate that the mutant DMK allele is expressed regardless of the number of CTG repeats and that the increase in DMK mRNA levels is due to elevated mutant mRNA levels. We postulate that elevated DMK levels explains the dominant inheritance pattern of DM. PMID- 8358431 TI - Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA. AB - Rad51, of Saccharomyces cerevisiae, is a homologue of recA of Escherichia coli and plays crucial roles in both mitotic and meiotic recombination and in repair of double-strand breaks of DNA. We have cloned genes from human, mouse and fission yeast that are homologous to rad51. The 339 amino acid proteins predicted for the two mammalian genes are almost identical and are highly homologous (83%) with the yeast proteins. The mouse gene is transcribed at a high level in thymus, spleen, testis and ovary and at a lower level in brain and other tissues. The rad51 homologues fail to complement the DNA repair defect of rad51 mutants of S. cerevisiae. The mouse gene is located in the F1 region of chromosome 2 and the human gene maps to chromosome 15. PMID- 8358432 TI - Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. AB - Fragile X syndrome is associated with massive expansion of a CGG trinucleotide repeat within the FMR-1 gene and transcriptional silencing of the gene due to abnormal methylation. Partial cDNA sequence of the human FMR-1 has been reported. We report here the isolation and characterization of cDNA clones encoding the murine homologue, fmr-1, which exhibit marked sequence identity with the human gene, including the conservation of the CGG repeat. A conserved ATG downstream of the CGG repeat in human and mouse and an in-frame stop codon in other human 5' cDNA sequences demarcate the FMR-1 coding region and confine the CGG repeat to the 5' untranslated region. We also present evidence for alternative splicing of the FMR-1 gene in mouse and human brain and show that one of these splicing events alters the FMR-1 reading frame, predicting isoforms with novel carboxy termini. PMID- 8358433 TI - Telomere capture stabilizes chromosome breakage. AB - Terminal deletions are found frequently in both malignancies and clinically recognizable deletion syndromes in man. Little is known, particularly in cancer, of the specific mechanisms which lead to the generation of deleted chromosomes or the process by which these broken chromosomes are stabilized. We demonstrate that several examples of apparent terminal deletions are, in fact, subtelomeric translocations which were not detectable using conventional cytogenetics. The unexpectedly high frequency of this phenomenon and the diversity of partner chromosomes involved in the subtelomeric translocations is consistent with a model in which telomere capture can stabilize chromosome breakage in man. PMID- 8358435 TI - Functional equivalence of human X- and Y-encoded isoforms of ribosomal protein S4 consistent with a role in Turner syndrome. AB - Several genes are found on both the human X and Y chromosomes in regions that do not recombine during male meiosis. In each case, nucleotide sequence analysis suggests that these X-Y gene pairs encode similar but nonidentical proteins. Here we show that the human Y- and X-encoded ribosomal proteins, RPS4Y and RPS4X, are interchangeable and provide an essential function: either protein rescued a mutant hamster cell line that was otherwise incapable of growth at modestly elevated temperatures. These findings are consistent with the hypothesis that RPS4 deficiency has a role in Turner syndrome, a complex human phenotype associated with monosomy X. PMID- 8358434 TI - 3,400 new expressed sequence tags identify diversity of transcripts in human brain. AB - We present the results of the partial sequencing of over 3,400 expressed sequence tags (ESTs) from human brain cDNA clones, which increases the number of distinct genes expressed in the brain, that are represented by ESTs, to about 6,000. By choosing clones in an unbiased manner, it is possible to construct a profile of the transcriptional activity of the brain at different stages. Proteins that comprise the cytoskeleton are the most abundant; however, a large variety of regulatory proteins are also seen. About half of the ESTs predicted to contain a protein-coding region have no matches in the public peptide databases and may represent new gene families. PMID- 8358436 TI - A high resolution deletion map of human chromosome Xp22. AB - We have developed a 32-interval deletion panel for human chromosome Xp22 spanning about 30 megabases of genomic DNA. DNA samples from 50 patients with chromosomal rearrangements involving Xp22 were tested with 60 markers using a polymerase chain reaction strategy. The ensuing deletion map allowed us to confirm and refine the order of previously isolated and newly developed markers. Our mapping panel will provide the framework for mapping new sequences, for orienting chromosome walks in the region and for projects aimed at isolating genes responsible for diseases mapping to Xp22. PMID- 8358437 TI - Heterozygous missense mutation in the rhodopsin gene as a cause of congenital stationary night blindness. AB - A number of mutations in the rhodopsin gene have been shown to cause both dominant and recessive retinitis pigmentosa. Here we describe another phenotype associated with a defect in this gene. We discovered a patient with congenital stationary night blindness who carries the missense mutation Ala292Glu. When coupled with 11-cis-retinal in vitro, Ala292Glu rhodopsin is able to activate transducin in a light-dependent manner like wild-type rhodopsin. However, without a chromophore, Ala292Glu opsin anomalously activates transducin. We speculate that the rod dysfunction in this patient is due to an abnormal, continuous activation of transducin by mutant opsin molecules in photoreceptor outer segments. PMID- 8358438 TI - Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1. AB - The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders characterized by onset with gait ataxia, dysarthria, dysmetria and dysdiadochokinesia. We have demonstrated previously genetic heterogeneity within these disorders by excluding the disease locus from the documented spinocerebellar ataxia locus (SCA1) on chromosome 6p in a large Cuban founder population. We now report the assignment of a second locus for ADCA (SCA2) to chromosome 12q23-24.1 following linkage analyses carried out for the Cuban pedigrees, with probable flanking markers D12S58 and phospholipase A2. Investigation of linkage to the interval containing SCA2 for seven French ADCA families, previously excluded from linkage to SCA1, provides preliminary data suggesting the existence of a third ADCA locus (SCA3). PMID- 8358439 TI - The gene for Machado-Joseph disease maps to human chromosome 14q. AB - Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Although it was first reported in families of Portuguese-Azorean descent, MJD has also been described in non-Azorean families from various countries, being one of the most common hereditary spinocerebellar degenerations. With the use of highly polymorphic microsatellite DNA polymorphisms, we have assigned the gene for MJD to the long arm of chromosome 14 (14q24.3-q32) by genetic linkage to microsatellite loci D14S55 and D14S48 (multipoint lod score Zmax = 9.719). PMID- 8358441 TI - Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome 11. AB - Familial hypertrophic cardiomyopathy (FHC) is a cardiac disorder transmitted as an autosomal dominant trait. FHC has been shown to be genetically heterogeneous with less than 50% of published pedigrees being associated with mutations in the beta myosin heavy chain (beta-MHC) gene on chromosome 14q11-q12. A second locus has recently been reported on chromosome 1. We examined the segregation of microsatellite markers in a French pedigree for which the disease is not linked to beta-MHC gene. We found significant linkage of the disease locus to several (CA)n repeats located on chromosome 11 (lod scores between +3.3 and +4.98). The data suggest the localization of the novel FHC gene in a region spanning 17 centiMorgans. PMID- 8358440 TI - Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. AB - Recent studies have demonstrated that a locus at 11p15.5 confers susceptibility to insulin dependent diabetes mellitus (IDDM). This locus has been shown to lie within a 19 kb region. We present a detailed sequence comparison of the predominant haplotypes found in this region in a population of French Caucasian IDDM patients and controls. Identification of polymorphisms both associated and unassociated with IDDM has allowed us to define further the region of association to 4.1 kb. Ten polymorphisms within this region are in strong linkage disequilibrium with each other and extend across the insulin gene locus and the variable number tandem repeat (VNTR) situated immediately 5' to the insulin gene. These represent a set of candidate disease polymorphisms one or more of which may account for the susceptibility to IDDM. PMID- 8358443 TI - [Hormonal treatments of normo-gonadotrophic oligoasthenospermia]. PMID- 8358442 TI - Identification of a common mutation in the carnitine palmitoyltransferase II gene in familial recurrent myoglobinuria patients. AB - Carnitine palmitoyltransferase (CPT) II deficiency is the most common inherited disorder of lipid metabolism affecting skeletal muscle. We have identified a missense mutation (Ser113Leu) in one patient with the classical muscular symptomatology. Transfection experiments in COS cells demonstrate that the mutation drastically depresses the catalytic activity of CPT II. The mutation results in normal synthesis but a markedly reduced steady-state level of the protein, indicating decreased stability of mutant CPT II. The Ser113Leu mutation is the most frequent cause of CPT II deficiency. The mutation can be detected easily by restriction analysis enabling molecular diagnosis of most patients and identification of heterozygous carriers. PMID- 8358444 TI - [Use of GnRh analogues in the treatment of female sterility]. PMID- 8358445 TI - [Ultrasonic mammography]. PMID- 8358446 TI - [What to do--what not to do with hirsutism]. PMID- 8358448 TI - [Cancer of the ovary and the treatment of infertility. Analysis of the article by Whittemore et al]. AB - Whittemore and al. recently published a general paper concerning the risk factors of ovarian cancer, combining the data from 12 epidemiological studies realised from 1979 to 1988. Three of these studies allowed to analyze the role of infertility treatments which were associated to an increased risk (odds ratio = 2.8), specially in nulligravid women (OR = 27.0). However potential bias could not be rejected, and information on drugs was too scanty, so that no definite conclusion could be drawn, even if the results were in accordance with the main physicopathogenical theories. In conclusion, it appears necessary to undertake a large epidemiological study, and, in the same time, even if patients must be reassured, to recommend attention to the doctors when prescribing infertility treatments. PMID- 8358447 TI - [Contraception and endometriosis]. AB - Contraception in women with endometriosis is unusual. In case of mild asymptomatic endometriosis all contraceptive methods may be used except predominant estrogenic action pills. In case of severe endometriosis if score is upon 70 or adhesion score upon 50 the patients are generally infertile. Contraception is not necessary. If scores are lower, medical treatment of endometriosis insure the contraception during the first six months. Afterwards an hydroxyprogesterone derivative pill such as cyproterone acetate, or a norpregnan derivative pill, or a combined estrogen progestogen pill, with predominant progestogen action (norgestrienon), or a monophasic pill containing norethisteron, or in case of metabolic diseases a pill containing gestoden, must be prescribed three out of four weeks. In case of adenomyosis, vaginal contraception is better. Perhaps in the next future, the new progestogen sterilant will be the best. PMID- 8358449 TI - [Microfertilization techniques: con]. AB - The actually used microfertilization procedures are exposed according to potential indications: flagellar immotility, previous unexplained failure of IVF, and oligo-asthenoteratozoospermia. Results of two prospective randomized studies are presented in case of severe asthenozoospermia associated with at least one previous failure of IVF. Evaluation of fertilization rates confirms that ZD does not improve IVF prognosis whereas SUZI could be used to enhance IVF results. Authors focused on major methodological criticisms raising about most of published series, on relatively low evolutive pregnancy rate (5.7%) and on the need of randomized prospective studies for judge real interest of assisted fertilization. PMID- 8358450 TI - [Pro clomiphene]. AB - Thanks to CC an important number of endocrine sterility has been cured. The antiestrogenic effect of CC has been accused to promote perturbations of cervical mucus secretion and endometrial receptivity. The different technics to assure correction of negative side effects while promoting optimal activity of clomiphene will be discussed in terms of modern evaluation methods. PMID- 8358451 TI - [Sperm and HIV]. AB - Screening and prevention are two major weapons in the fight against AIDS. Procreation of couples where the spouse is seropositive poses a serious ethical social and epidemiological problem. We have consequently established a list of the current biological data concerning HIV in the sperm at the level of non germinal cells, seminal plasma and spermatozoa and of the clinical data on the transmission of the virus during sexual intercourse and insemination. Finally, we have presented the results of the research on predictable factors of the infectiousness of sperm. After this analysis, we consider the possibilities open to the medical corps: dissuasion, ovulation monitoring, insemination with the husband sperm, IVF and insemination with hope to be able to participate in the debate which must lead to a clear concerted and coherent position on the part of the medical corps, at least on a national level. PMID- 8358452 TI - [Fertility tests (hamster, electronic microscopy): are they useful?]. AB - Tests of sperm function are often considered to be able to predict the in vivo or in vitro fertility of a given patient although they only assess part of the process of sperm fertilizing ability. It appears from the literature, that the sperm penetration assay (SPA) which investigates the sperm fusiogenic and nuclear functions cannot accurately predict the in vivo fertility and there is still much debate on the reliability of its correlation with in vitro fertilization (IVF) principally in cases of severe sperm deficiency. With the development of new techniques of assisted fertilization, by-passing the zona pellucida, a test of sperm fusion, hetero or homospecific as well, could be interesting. Considering sperm ultrastructure and beyond some specific morphological alterations of the whole sperm population that can be responsible for the infertility, such studies were not able, as yet, to reveal significative differences between semen fertile in vitro or not. PMID- 8358453 TI - [Chronicle of functional pain: chronic pelvic pains]. AB - Chronic pelvic pains are one of the most frequent complaints in our daily gynecological practice, motivating at least a quarter of our consultants. As it usually puts the practitioner ill at ease in a difficult situation, we will try to understand the meaning of those particular pains, thus defined: a duration outlasting 6 months and the absence or the ineffective suppression of any organic -somatic--substratum. But every alleged pain is real and true, and we must work on that. To validate such suffering, to accept such repetitive complaints, can also be a therapeutic medical approach, even if it is less gratifying for the gynecologist, and certainly less customary. PMID- 8358454 TI - [University of Quebec at Montreal. Psychosexuality of childhood and adolescence: trends in research]. AB - This paper reviews the literature on child and adolescent psychosexuality. It intends to identify the major trends in contemporary research in the field of psychosexual development. Reviewing first, the theories of the child and adolescent development, in exploring the psychosexuality dimension, it shows afterward that in the actual state of research two thematics are privileged in empirical literature: "gender" and "sexual and contraceptive attitudes-values behaviours". These thema are mainly studied in the descriptive correlation researches which focus on gender identity, gender roles, gender differences in one part and on initiation to first sexual relationships, its predictors and consequences on the other part. In a whole, these data are factual rather than developmental in nature. These one identifies the facts inherent to development but they rarely shows the interaction between these facts nor their evolution in the courses of time. This literature review does not cover all the interests touched by the searchers in the field nor it pretend to fully examine the research content exposed in this paper. It limits itself to identify the major trends in the contemporary research and to offer some indication for the future. PMID- 8358455 TI - [Prostatic utricle, a rare but potentially curable cause of male sterility]. AB - This case report describes a patient presenting a cyst of the prostatic utricule that was detected during assessment for sterility and removed surgically. A review of the pertinent literature is proposed. Azoospermia or severe oligospermia associated with a low ejaculation volume are the main manifestations. Transrectal ultrasonography is the diagnostic examination of choice. In most cases incision of the mouth of the utricule promptly abolishes sterility and enables fertilization. PMID- 8358456 TI - [Respective roles of thecal and granulosa cells in the morphogenesis of the corpus luteum]. AB - Studies on human ovary embryogenesis and adult post-ovulatory surgically resected ovaries allowed the authors to propose a new conception on the genesis of corpus luteum: large luteal cells would be derived from theca interna cells and small luteal cells would come from externa theca cells. So there would be a structural unity of luteal tissue which might explain steroidogenesis potential of these two types of cells, derived both from the same ovarian stroma. On the other hand if granulosa cells played an important function in bio-conversion of androgens to oestradiol by aromatase activity before ovulation, their role is over after the expulsion of the oocyte out of the follicle; derived from primitive sex cords of coelomic mesothelium origin, granulosa cells act to support and surround the oocyte; they disappeared at the disappearance of the oocyte from the follicle. PMID- 8358457 TI - Interesting times: managed critical care. PMID- 8358458 TI - Determining AACN's research priorities for the 90s. AB - The American Association of Critical-Care Nurses completed a three-phased process of priority identification for critical care nursing research. In phase 1, a 78 item survey was generated following a comprehensive review of potential research topics. In phase 2, approximately 1000 critical care nurses rated each item on the survey for importance to critical care nursing. Based on these results, the AACN Research Committee formulated a clinical and a nonclinical (contextual) list of research topics. Each list contained 25 topics. In phase 3, topics were given final rankings at a 1-day Consensus Conference on Research Priorities. Both Likert-type and magnitude estimation scaling were used to determine priority ranking of items on each list. As a result, both clinical and contextual research priorities were established for AACN. PMID- 8358460 TI - Pilot study: validating staff nurses' observations of sleep and wake states among critically ill patients, using polysomnography. AB - BACKGROUND: Effective management of sleep pattern disturbance begins with accurate assessment of the patient's sleep and wake states. OBJECTIVE: The purpose of this study was to validate staff nurses' observations of sleep and wake states among critically ill adult patients, using polysomnography. SAMPLE AND SETTING: The sample consisted of 21 adult patients with multisystem diagnoses in a 10-bed medical intensive care unit in a 540-bed acute care teaching hospital. METHOD: Each staff nurse caregiver observed a single patient for the entire data collection period of 4 hours, with a total of 15 nurses participating in the study. A total of 340 observations were made, with the possibility of 17 observations per patient. Nursing observations were made every 15 minutes on each patient and compared to the actual patient state as measured by polysomnography. RESULTS: Nurses' assessments were correct 81.9% of the time. CONCLUSIONS: There is some basis for using staff nurses as observers of sleep and wake states. Increased credence can be placed on nursing assessments and diagnosis of sleep pattern disturbance, resulting in more timely and effective management of the problem. PMID- 8358459 TI - Effects of patient-controlled analgesia on postoperative anxiety in elderly men. AB - OBJECTIVE: To determine whether the use of patient-controlled analgesia vs intramuscular injections improves postoperative psychological parameters, particularly anxiety. DESIGN: Randomized, controlled trial of patient-controlled analgesia vs as-needed intramuscular morphine with pre- and postoperative assessments of pain, mental status, narcotic use, anxiety and mood states. SETTING: General surgical wards and surgical intensive care unit at a Veterans Administration hospital. PATIENTS: Eighty-three elderly, chronically ill males undergoing major elective surgery. INTERVENTION: Subjects randomized to receive postoperative patient-controlled analgesia vs as-needed intramuscular morphine. Pre- and postoperative assessments of State-Trait Anxiety Inventory, McGill Dartmouth Part IV and Short Portable Mental Status Questionnaire. Pain (using linear analog scale), sedation score and narcotic use assessed every 4 hours for 72 hours. RESULTS: No differences were found in state anxiety or self-perceived mood states. Postoperative state anxiety was found to relate most closely to preoperative anxiety and postoperative complications, rather than method of analgesia or severity of pain. However, patient-controlled analgesia subjects had significantly improved analgesia and increased satisfaction. CONCLUSION: The use of patient-controlled analgesia does not significantly alter the measured psychological parameters, compared with intramuscular injections. Improved analgesia is the result of pharmacologic effects, independent of psychological factors. PMID- 8358461 TI - Room-temperature thermodilution cardiac output: proximal injectate lumen vs proximal infusion lumen. AB - OBJECTIVE: To assess the accuracy of room-temperature thermodilution cardiac output measurements from the venous infusion port. DESIGN: Central venous port cardiac output measurements were compared with venous infusion port measurements in 48 right-heart catheters. INTERVENTION: Three 10-mL injections of 5% dextrose in water were made through each port. The order of port injection was random. RESULTS: The cardiac outputs were 5.8 +/- 1.8 L/min from both ports, with no difference between ports (paired t test). CONCLUSION: Room-temperature thermodilution cardiac output determinations from the venous infusion port can be used in place of central venous port cardiac outputs if the central venous port becomes nonfunctional. PMID- 8358462 TI - Liver transplantation for acute hepatic failure: a review of clinical experience and management. AB - OBJECTIVE: The purpose of this review was to examine and describe the clinical experience and outcomes of liver transplantation in humans for acute fulminant hepatic failure. DATA SOURCES: A review of the literature since 1980 using Medline was done to identify clinical reports including case study reports. STUDY SELECTION: Clinical reports were included if they stated the number of patients in a given time frame who were evaluated and/or received a transplant for acute hepatic failure and any other outcome data such as the number of those who recovered without a transplant and who died in the operative period. Twenty-two reports were identified that met the selection criteria. Data were reported inconsistently. No ex post facto reports that examined factors relevant to clinical outcomes were identified. CONCLUSIONS: Acute hepatic failure is considered an acceptable indication for liver transplantation based on the opinions expressed by the leading experts in the field as currently reported in the literature and at professional meetings. Data is limited, however, on outcomes and factors contributing to successful outcomes. PMID- 8358463 TI - Common infections in heart transplant patients. AB - Infection is the primary cause of morbidity and mortality following cardiac transplantation because of the strict immunosuppressive regimens patients follow. In the immediate postoperative phase, patients are more susceptible to infection because of interruption of their external barriers to infection. Cardiac transplant recipients are most likely to succumb to infections caused by cytomegalovirus, Epstein-Barr virus and bacterial organisms, especially staphylococcus. Fungal, protozoal and herpes simplex infections are also frequently troublesome to the transplant recipient. Critical care clinicians can control the incidence of infection in the cardiac transplant population by initiating measures to maintain external barriers, monitoring the patient for early signs of infection, and instituting appropriate isolation techniques. PMID- 8358464 TI - Case study: heart transplantation--increased incidence of acute rejection in female recipients. AB - Although the precise link between the increased incidence of allograft rejection in female heart transplant recipients remains uncertain, various gender-specific characteristics may predispose women to earlier rejection episodes. Critical care practitioners must be cognizant of the underlying immunologic factors that indicate higher risk in these recipients. Until the ideal treatment for cardiac rejection is discovered, identifying pertinent immunologic factors, attending to subtle symptoms, obtaining serial endomyocardial biopsies and initiating prompt, additional aggressive immunosuppressive protocols remain paramount in rendering quality patient care. Research must continue to elicit more specific tissue typing antigens and more selective immunosuppressive agents that will ultimately result in prolonged survival of all heart transplant recipients. PMID- 8358466 TI - A case report of postpneumonectomy syndrome. PMID- 8358465 TI - A preliminary investigation of opinions and behaviors regarding advance directives for medical care. AB - BACKGROUND: Advance directives are a means of promoting patient autonomy in end of-life decisions but are used infrequently. A recent federal law requires healthcare organizations to provide information to patients about advance directives. This study explored attitudes and behaviors related to the use of advance directives in three areas: familiarity with advance directives, reasons for completing or not completing advance directives and preferences for receiving information about advance directives. METHODS: A questionnaire was administered by personal interview to a nonrandomized convenience sample of 46 inpatients and 50 outpatients at a large, tertiary care, urban academic medical center in the summer of 1991. RESULTS: Most respondents (77%) had heard of either the living will or durable power of attorney for healthcare, but only 52% correctly understood the purpose of these documents. Twenty-nine percent of the sample had executed an advance directive. Those who had advance directives were older and considered themselves less healthy than did those without advance directives. Unfamiliarity with advance directives and procrastination were cited most often as reasons for not having an advance directive. Most subjects (65%) had spoken with someone, usually a family member or close friend, about preferences for treatment during a critical illness. Although they had rarely discussed advance directives, 83% anticipated that they would be comfortable doing so with a physician or a nurse. CONCLUSIONS: Advance directives are used infrequently to document treatment preferences. The success of programs to promote greater use of advance directives depends on a clearer understanding of the factors that influence both decision and action to execute an advance directive. Patients claim to be comfortable in discussing the topic and prefer that such discussions occur in the outpatient setting. PMID- 8358467 TI - PTCA in elderly patients: hospital events. AB - BACKGROUND: Medical treatment of the elderly is changing to include the aggressive management of coronary artery disease with percutaneous transluminal coronary angioplasty. OBJECTIVE: The purpose of this study was to review major hospital events of patients aged 70 years or more, who underwent a first percutaneous transluminal coronary angioplasty. METHODS: A retrospective medical record review was done of 246 consecutive patients of 70 years or more, from January 1985 to December 1988, at a tertiary care community hospital. Adverse events and the factors that influenced outcome were identified. RESULTS: Of 246 patients (age range, 70-85 years, mean = 73.6), 19 died, 4 had a cerebral vascular accident, 11 had a transfusion and 11 underwent coronary artery bypass grafting. Sixteen patients had acute vessel closure and 8 died. Twenty-five patients had one event and 21 patients had more than one. DISCUSSION: The event rate after percutaneous transluminal coronary angioplasty in the elderly is high. CONCLUSIONS: Knowledge of the factors that influence adverse events (diagnostic category, success of procedure, degree of coronary artery disease and age) will assist the critical care team to plan and implement appropriate care. PMID- 8358468 TI - Survey of the degree to which critical care nurses are performing current procedural terminology-coded services. PMID- 8358469 TI - An open door policy in ICU. PMID- 8358470 TI - Regulations and critical care. PMID- 8358471 TI - Nontraditional nursing education programs. PMID- 8358472 TI - Doing the thing right: assumptions and assessment in hemodynamic monitoring. PMID- 8358473 TI - Indirect blood pressure measurement: a need to reassess. AB - BACKGROUND: Indirect blood pressure measurement is the assessment tool used most frequently in epidemiological studies and hypertension management in the population at large. OBJECTIVE: To review indirect blood pressure measurement within the context of nursing practice. RESULTS: Nurses are not following recommended American Heart Association measurement guidelines. CONCLUSION: A national program of certification in indirect blood pressure measurement, similar to that of basic and advanced cardiac life support, is needed. An initial approach to evaluating present practice is also suggested. PMID- 8358474 TI - ST segment monitoring for coronary artery reocclusion following thrombolytic therapy and coronary angioplasty: identification of optimal bedside monitoring leads. AB - BACKGROUND: Bedside ST segment monitors analyze only one precordial lead and one, two or three limb leads. The precordial lead V1 (or V6 if V1 is not feasible) has been recommended for bedside monitoring because of its value in diagnosing cardiac rhythms with a wide QRS complex. Thus, the remaining lead choices for ST monitoring are limited to the six limb leads. PURPOSE: To determine which of the limb leads in conjunction with V1 or V6 provides the greatest sensitivity for myocardial ischemia, a study was undertaken. METHOD: A total of 30 vessel-unique ischemic episodes were analyzed prospectively using continuous 12-lead electrocardiographic recordings in patients with acute myocardial infarction (n = 2) and patients undergoing coronary angioplasty (n = 25). RESULTS: Ischemic changes were evident in all cases using the full 12-lead electrocardiogram. Right coronary artery-related ischemia was detected in all cases using a single-lead III or aVF. In the group as a whole, the best combinations were: V1 + aVF, V1 + III, V6 + III, and V6 + aVF. Two patients developed sudden coronary artery reocclusion in the cardiac care unit after successful angioplasty. In both, leads identified in the cardiac catheterization laboratory as sensitive for recording ischemia were excellent choices for detection of reocclusion in the cardiac care unit. CONCLUSIONS: 12-lead electrocardiogram recordings during coronary angioplasty balloon inflation provide excellent guidance for postprocedure lead selection decisions. The most valuable limb leads for detecting ischemia due to abrupt artery closure are leads III and aVF, either of which is more sensitive than the routinely monitored lead II. The precordial leads valuable for arrhythmia monitoring, V1 and V6, are seldom sensitive in detecting ischemia in these patients. PMID- 8358475 TI - Chest tube stripping in pediatric oncology patients: an experimental study. AB - BACKGROUND: Stripping of chest tubes to promote drainage of the thorax of postthoracotomy patients has been routine practice, based on tradition. Recent published findings indicate that significant negative pressures are generated in the tube during stripping that could cause pain, bleeding and possible damage to the patient's lung tissue. OBJECTIVE: To determine whether pediatric oncology patients whose chest tubes were not stripped would differ in frequency of pain, fever or lung complications from patients who underwent routine tube stripping. METHODS: Data were collected at multiple points during the first 72-hour postoperative period from 16 patients assigned to the stripped or unstripped groups. Pain was measured by the Faces Pain Scale and the Visual Analogue Scale; temperature, by electronic thermometer; and lung complications, by stethoscope and radiographs. Both groups, which were comparable for age, primary diagnosis and prior history of lung problems, received identical supportive nursing and medical care, with the physicians blind to group assignment. RESULTS: The two groups did not differ significantly in frequency of pain, incidence of fever, breath sounds or radiographic findings across measurement points. A strong correlation was found between the pain scores using the two instruments. DISCUSSION: Patients whose tubes were not stripped did not have an increased risk of infection or lung complications. Study findings indicated that stripping did not increase the frequency of pain. CONCLUSIONS: Stripping of chest tubes as a routine postoperative measure is questioned. PMID- 8358476 TI - Consenting to DNR: critical care nurses' interactions with patients and family members. AB - OBJECTIVE: To investigate the process of consenting to do-not-resuscitate status from the perspective of critical care nurses who have been involved with patients and/or family members during their decision. METHOD: A network sample of 22 critical care nurses, with at least 1 year's experience in a critical care unit and self-reported multiple experiences with the do-not-resuscitate consent process, participated in the study. Semistructured, formal interviews were used to collect data. All interviews were tape recorded and transcribed verbatim. The grounded theory method was used to collect and analyze data. RESULTS: The analysis revealed a core category: consenting to do-not-resuscitate status. Integrated into the process were intervening conditions that further explained the process: the meaning of "do not resuscitate," the importance of time/timing in the process, the nurse's role and conflict issues that arose during the process of consenting to do-not-resuscitate status. CONCLUSIONS: The theoretical model developed in this study provides a framework to describe the role of critical care nurses in the do-not-resuscitate process. In addition, a description of the categories provides information for nurses, especially novice nurses, to consider when caring for patients and families who are in the process of making decisions concerning resuscitation. PMID- 8358477 TI - Organ donation: comparison of nurses' participation in two states. AB - BACKGROUND: The number of organs available for transplantation in the United States is insufficient, and the donor rate in New Jersey is particularly low. OBJECTIVES: To explore reasons nurses do or do not refer organ donors and to identify factors that contribute to differences in referral rates in New Jersey and Pennsylvania. METHODS: Registered nurses (N = 976) in 57 nongovernmental acute care hospitals, primarily in emergency departments and intensive care units, completed a questionnaire that focused on their knowledge and participation in the organ procurement process. RESULTS: Two-thirds of the subjects said they had participated in organ procurement. Pennsylvania nurses had a significantly higher involvement rate than New Jersey nurses. Pennsylvania nurses were also slightly more knowledgeable about the process. A higher proportion of nurses in both states who attended continuing education programs participated. CONCLUSIONS: Nurses need more inservice education regarding policies and procedures for organ donation. PMID- 8358478 TI - Effects of lung hyperinflation and presence of positive end-expiratory pressure on arterial and tissue oxygenation during endotracheal suctioning. AB - PURPOSE: To explore the effects of endotracheal suctioning on mixed venous oxygen tension and other measures of arterial and tissue oxygenation, to determine if these would be clinically useful outcome measures of endotracheal suctioning. BACKGROUND: Measuring arterial oxygenation only as an outcome of endotracheal suctioning can be misleading in that it may appear adequate in the presence of marked decreases in mixed venous oxygen tension, a good indicator of the adequacy of tissue oxygenation. METHODS: Eighteen instrumented and oleic acid-injured animal models of acute respiratory failure undergoing closed-system endotracheal suctioning were studied according to a 2 x 2 factorial design to measure the effects of oxygen inflations at tidal volume or 135% of tidal volume either in the presence or absence of positive end-expiratory pressure. RESULTS: Using multivariate analysis of variance for repeated measures, protocol by time effects for mixed venous oxygen tension, arterial oxygen saturation, arterial oxygen tension, oxygen delivery and oxygen extraction ratio were statistically significant. Changes in mixed venous oxygen tension and arterial oxygen saturation were parallel. CONCLUSIONS: Continuous measurement of mixed venous oxygen tension allows the calculation of oxygen delivery and oxygen extraction ratio, which provide a better estimation of the effects of endotracheal suctioning on tissue oxygenation than arterial oxygen tension alone. PMID- 8358480 TI - The indirect patient care effect of a unit-based clinical nurse specialist on preventable pulmonary complications. AB - PURPOSE: To examine the indirect effect of a unit-based expert nurse on the incidence of preventable pulmonary complications, which were defined as malpositioned endotracheal tube and inadvertent extubation. DESIGN: A nonequivalent control group/separate samples pretest/posttest design was used to test differences in the incidence of preventable pulmonary complications before and after a 6-month intervention by a unit-based expert nurse in the experimental unit. Retrospective medical record audits were used to collect data on all consecutive admissions to the experimental and control units in March and April of years 1 and 2. RESULTS: Estimated risk ratios demonstrated a significant reduction in preventable pulmonary complications in the experimental unit after the test, even though the acuity was significantly higher in posttest patients. It was concluded that indirect patient care by a unit-based clinical nurse specialist can reduce the incidence of preventable pulmonary complications. PMID- 8358479 TI - The effect of saline lavage prior to suctioning. AB - OBJECTIVE: To determine the effect on oxygen saturation of instilling a saline bolus into artificial airways prior to suctioning, as measured by pulse oximeter. DESIGN: Quasi-experimental, single-case, counterbalanced design. SETTING: The surgical, medical and coronary intensive care units of a federal, teaching medical center. SUBJECTS: Subjects were 40 men, more than 40 years old, in need of intensive care nursing and mechanical ventilation. INTERVENTIONS: Subjects were suctioned as needed for 24 hours. A 5-mL saline bolus was instilled every other time the subject was suctioned. Outcome measurements were done immediately before and after suctioning and at 1-minute intervals for 5 minutes after suctioning. MAIN OUTCOME MEASURES: Noninvasive oxygen saturation values. RESULTS: The instillation of a saline bolus was found to have an adverse effect on oxygen saturation that worsened over time. Significant changes in oxygen saturation as a result of saline bolus instillation were found at 2,3,4 and 5 minutes after instillation. CONCLUSIONS: These results indicate that instilling saline prior to suctioning has an adverse effect on oxygen saturation. These results support the recommendation that the practice of instilling saline prior to suctioning should be abandoned as a routine procedure. More study is needed to investigate whether a specific group of patients may actually benefit from this procedure. PMID- 8358481 TI - Visit preferences of middle-aged vs older critically ill patients. AB - OBJECTIVE: To differentiate between middle-aged and older adults' visiting preferences in critical care settings. DESIGN: Patients' preferences for visiting, perceptions of illness severity and extent of fatigue associated with visiting and an objective measurement of illness severity while in critical care were surveyed within 3 days after transfer from the critical care unit. SETTING: Interviews occurred on the transitional care units with patients who transferred from either the coronary care or surgical intensive care units in a large Northeast teaching hospital. PATIENTS: Fifty-three middle-aged (35 through 65 years) and 46 older (over 65 years) patients were surveyed (N = 99). RESULTS: Both middle-aged and older patients consistently wanted to limit the number of visitors to two or three persons per visit. Compared with middle-aged patients, a greater proportion of older patients preferred to limit visits to once a day and wanted the visit length to be unlimited. A greater proportion of older coronary care unit patients preferred to limit visits to two times a day than older surgical unit patients. CONCLUSIONS: Middle-aged and older patients differed in their preferences for visits, with sufficient variation in responses to warrant tailoring visits to the unique preferences of patients based on age and clinical setting. PMID- 8358482 TI - "I want to die, I think": a case study in clinical ethics and determination of truth. PMID- 8358483 TI - The importance of magnesium in cardiovascular disease. PMID- 8358484 TI - Intelligent monitoring and control of dynamic physiological systems. PMID- 8358485 TI - Model-based diagnosis in intensive care monitoring: the YAQ approach. AB - YAQ is an ontology for model-based reasoning in physiologic domains. YAQ is based on a hybrid algebra of qualitative and numerical values, and is designed to benefit from the rich and ever-changing nature of information available in a critical care monitoring environment. The focus of the project is on diagnosis of clinical conditions, prediction of the effects of therapy, and therapy management assistance. Two models of diagnosis are implemented in YAQ: diagnosis based on associations, and model-based diagnosis. The ontology is applied to the domain of ventilator management in infants with respiratory distress syndrome (RDS). The article describes the diagnostic capabilities of YAQ, illustrates these concepts on examples taken from actual patient records, and reports the results of an evaluation of the diagnostic performance on the RDS/assisted ventilation domain model. PMID- 8358486 TI - Guaranteeing real-time response with limited resources. AB - Unanticipated problems detected by patient-monitoring systems may sometimes require real-time response in order to provide high-quality care and avoid catastrophic outcomes. In this paper, we present an approach for guaranteeing a response to such events by a monitoring agent even in situations where we have limited problem-solving resources. We show that an action-based hierarchy can accomplish this goal. We also analyze the performance of this hierarchy under varying resource availability and discuss decision-theoretic approaches to enable us to best structure such a hierarchy. We also describe an implementation of these ideas, called ReAct, in the BB1 architecture. All the ideas are illustrated with examples from the surgical intensive care unit (SICU). PMID- 8358487 TI - The design and implementation of a ventilator-management advisor. AB - VentPlan is an implementation of the architecture developed by the qualitative quantitative (QQ) research group for combining qualitative and quantitative computation in a ventilator-management advisor (VMA). VentPlan calculates recommended settings for four controls of a ventilator by evaluating the predicted effects of alternative ventilator settings. A belief network converts clinical diagnoses to distributions on physiologic parameters. A mathematical modeling module applies a patient-specific mathematical model of cardiopulmonary physiology to predict the effects of alternative ventilator settings. A decision theoretic plan evaluator ranks the predicted effects of alternative ventilator settings according to a multiattribute-value model that specifies physician preferences for ventilator treatments. Our architecture allows VentPlan to interpret quantitative observations in light of the clinical context (such as the clinical diagnosis). We report a retrospective study of the ventilator-setting changes encountered in postoperative patients in a surgical intensive-care unit (ICU). We conclude that the QQ architecture allows VentPlan to apply a patient specific physiologic model to calculate ventilator settings that are optimal with respect to a decision-theoretic value model describing physician preferences for setting the ventilator. PMID- 8358488 TI - Physiological applications of consistency-based diagnosis. AB - This research attempts to span the gap between the AI in medicine (AIM) and consistency-based diagnosis (CBD) communities by applying CBD to physiology. The highly-regulated nature of physiological systems challenges standard CBD algorithms, which are not tailored for complex dynamic systems. Extensions of CBD to dynamic domains have relied upon complete quantitative dynamic simulation for behavior prediction. However, dynamic simulations, particularly by continuous systems, tend to inundate key CBD processes (such as truth maintenance and information-theoretic testing) with a deluge of temporal information. To combat this problem, we separate static from dynamic analysis so that CBD performs static diagnosis at a selected set of time slices. Knowledge of the qualitative behavior of physiological regulators is then used to link static intra-slice diagnoses into a complete dynamic account of the progression of a physiological condition. This provides a simpler approach to CBD of dynamic systems while adding a new capability to CBD: the detection of dynamic faults (i.e. those that do not necessarily persist throughout diagnosis). This paper describes (a) a few of the problems underlying CBD extensions to dynamic systems, (b) our hybrid static-dynamic, qualitative-quantitative approach, (c) our implemented IDUN system, (d) IDUN's diagnosis of volume-loading hypertension, (e) the generalization of IDUN's modeling perspective to the compartmental ontology, and (f) IDUN's use of compartmental models to diagnose acidosis. PMID- 8358489 TI - European research efforts in medical knowledge-based systems. AB - This article describes the major projects going on in Europe in the field of Artificial Intelligence in Medicine. The important role of the Commission of the European Communities in providing the needed resources is stressed throughout the paper. Particular attention is given to the methodological and technological issues addressed by the European research teams, since the results which these teams accomplish are fundamental for a more extensive diffusion of knowledge based systems in real medical settings. The variety of medical problems tackled shows that there is no field of medicine where the potential of advanced informatics technologies has not yet been assessed. PMID- 8358490 TI - Exploring the relationship between rationality and bounded rationality in medical knowledge-based systems. AB - If our goal in Artificial Intelligence in Medicine (AIM) is to engineer systems health-care providers will both use and, in the process, improve their performance, we must concentrate on the development of causal theories of knowledge and problem solving. One broad direction in pursuing this goal is understanding the relationships between existing models of rationality and bounded rationality for similar tasks. Models of rationality refer to those approaches in which the optimal properties of the models are deductively provable, i.e. in which the processing is rational. Representative models of rationality used in AIM are deductive logical models, statistical models such as Bayesian inference models, and decision-analytic models. Models of bounded rationality are those which do not guarantee such optimal properties nor yield to deductive correctness proofs. These models have their roots in cognitive psychology. In this article we show how explicating the relationship between models of rationality and bounded rationality might be done in the case of abductive tasks in medicine. This is done by positioning these modeling approaches within the same framework (an abstract computational model) and interpreting in this context both computational complexity results concerning the nature of the task and empirical results studies of human problem-solving behavior. PMID- 8358491 TI - Neural computation in medicine. AB - During the last decade there has been a great revival of interest in neural modelling. Powerful new computational methods have resulted from work in this area and are being applied to an increasing range of medical problems. This paper briefly explains the nature of a neural model and then reviews work in neural computation involving problems in medical informatics (e.g. expert systems) and modelling of psychiatric and neurological phenomena. The state of the art is assessed, and speculation about future developments is given. PMID- 8358492 TI - On the soundness and safety of expert systems. AB - The problems of developing sound and safe expert systems are discussed, with particular reference to medicine. The concepts, notations, methods, results and technologies which have emerged from the study of mathematical logic as a computational paradigm offer many benefits for improving the quality of expert systems. Logic programming offers a better discipline for design, specification and implementation than ad hoc development methodologies. When logic programming is combined with software engineering methods, such as a software development life-cycle, the probability of routinely developing large-scale yet efficient and sound applications will be increased. However, although soundness is a necessary property of any technology it is not sufficient for assuring safety. Established methods for improved software safety are discussed, and a number of approaches to improving the safety of medical expert systems is identified. The possibility of introducing an appropriately extended life-cycle, and the potential benefits of a formal theory of safety are discussed. PMID- 8358493 TI - Artificial intelligence in medicine: state-of-the-art and future prospects. PMID- 8358494 TI - The adolescence of AI in medicine: will the field come of age in the '90s? AB - Artificial intelligence in medicine (AIM) has reached a period of adolescence in which interactions with the outside world are not only natural but mandatory. Although the basic research topics in AIM may be those of artificial intelligence, the applied issues touch more generally on the broad field of medical informatics. To the extent that AIM research is driven by performance goals for biomedicine, AIM is simply one component within a wide range of research and development activities. Furthermore, an adequate appraisal of AIM research requires an understanding of the research motivations, the complexity of the problems, and a suitable definition of the criteria for judging the field's success. Effective fielding of AIM systems will be dependent on the development of integrated environments for communication and computing that allow merging of knowledge-based tools with other patient data-management and information retrieval applications. The creation of this kind of infrastructure will require vision and resources from leaders who realize that the practice of medicine is inherently an information-management task and that biomedicine must make the same kind of coordinated commitment to computing technologies as have other segments of our society in which the importance of information management is well understood. PMID- 8358495 TI - Graphical knowledge acquisition for medical diagnostic expert systems. AB - Like many textbook authors use text systems for writing their books, expert system authors should have easy to use knowledge acquisition systems for entering and testing their knowledge bases by themselves without much help from 'knowledge engineers'. In this paper, we report on a graphical knowledge acquisition tool (CLASSIKA) based on an expert system shell for heuristic classification (MED2) and designed for direct use by domain experts. We demonstrate how the system has been used for building a rather large expert system for diagnosing rheumatology diseases which is now being tested in clinical use. PMID- 8358496 TI - Medical decision making based on inductive learning method. AB - Medical decision making based on inductive learning has been studied in order to collect experience necessary for practical use of such methods in clinical and epidemiological work. The decision trees have been constructed by using the modified Quinlan's approach based on choosing relevant attributes according to their informativity. An inductive learning software tool, ASSISTANT Professional, has been used for experimenting. The variability in results has been studied under varying learning conditions. Two sets of data have been chosen for learning experiments: from a study on rheumatoid factors in patients with rheumatoid arthritis, and from an epidemiological investigation of aging. The results of this study indicate the necessity to determine inductive learning parameters for each particular problem. The pruning procedure is always recommended as it eliminates redundant elements in the tree. In problems with greater number of attributes, however, pruning itself is not guaranteeing satisfactory solutions. Interventions like the change of the minimal weight threshold might improve the situation. If these precautions are met, the method of inductive learning seems to be a useful guide in practical clinical and epidemiological decisions. PMID- 8358497 TI - Automatic knowledge base refinement: learning from examples and deep knowledge in rheumatology. AB - MESICAR is a second generation expert system which contains very general descriptions of rheumatological disorders in the primary medical care field. With the help of a detailed hierarchical description of the human anatomy the system is able to support diagnostic decisions. The paper describes how machine learning techniques are used to automatically construct more specific disease descriptions for common, frequently occurring cases. The system MESICAR-LEARN implements a learning method which integrates analytical and empirical learning techniques. Cases diagnosed by MESICAR form the training examples, and MESICAR's knowledge base is used as domain theory. The learned concepts are integrated into a hierarchy of disease descriptions. They support efficient and fast reasoning on common cases in addition to the general diagnostic support afforded by MESICAR's deep knowledge. PMID- 8358498 TI - Consistency enforcement in medical knowledge base construction. AB - Some aspects of knowledge base creation can be partially or completely automated, resulting in higher quality and smaller effort. Computer assistance is particularly valuable in ensuring the internal consistency of a knowledge base. The article describes several techniques for consistency enforcement in QMR-KAT, an interactive knowledge base editor for the INTERNIST-I/QMR medical knowledge base. Two strategies that improve consistency are applicable to a wide range of situations. The first strategy prevents simple (but common) inconsistencies. The second strategy reveals facts that are potentially (but not necessarily) inconsistent with known data, and may require further evaluation. Both strategies use the contents of the existing knowledge base in the evaluation of new facts. PMID- 8358499 TI - Inferential knowledge acquisition. AB - This paper describes the approach we are pursuing for modeling inferential processes in knowledge-based systems. It is aimed at overcoming the lack of generality affecting many of the systems described in the literature. This mainly happens since the problem-solving method adopted by those systems is too closely tied to the particular domain problem over which the method itself has been modeled. We also describe a system called M-KAT (Medical Knowledge Acquisition Tool) which is useful in simplifying the process of acquiring inferential knowledge. M-KAT relies on an epistemological model of medical reasoning which represents a generalization of most of the problem-solving methods adopted in medical knowledge-based systems. The metarules formalism has been adopted as a mean for representing inferential knowledge and making its acquisition easier, thus allowing the computational implementation of the epistemological model of medical reasoning. PMID- 8358500 TI - Specification of models in large expert systems based on causal probabilistic networks. AB - Problems involved in the specification of large expert systems are discussed. In the specification of causal probabilistic networks conditional probability tables for all nodes have to be provided. These conditional probability tables can often be described by models that specify the nature of interaction between nodes. Various types of models are described and a program that handles such models is presented. Large causal probabilistic networks often contain several copies of identical tables or structures. A header facility that provides common definitions of such repeated elements is proposed. This facility makes specifications much shorter and easier to construct and maintain. PMID- 8358501 TI - Calbindin D-28k and monoamine oxidase A immunoreactive neurons in the nucleus basalis of Meynert in senile dementia of the Alzheimer type and Parkinson's disease. AB - In this study, calbindin D-28k (CaBP), monoamine oxidase A (MAO A) and nerve growth factor receptor (NGFr) immunoreactivities were investigated in the nucleus basalis of Meynert (NbM) in patients with senile dementia of the Alzheimer type (SDAT), with Parkinson's disease (PD) with or without dementia, and in controls. Immunocytochemistry using specific antibodies in differing serial sections was employed, and cell counts and NbM nuclear volume measurements were made. Most of the large multipolar NbM neurons showed CaBP immunoreactivity in the cytoplasm of their somata, dendrites and axons. In adjacent, NGFr-reacted sections, the large NbM neurons were also found to be intensely immunoreactive for NGFr on their cellular surfaces. In addition, a subpopulation of large NbM neurons and glial cells were found to be immunoreactive for MAO A. The number of CaBP immunoreactive (CaBP-i) neurons was decreased by an average of 55% in the 6 SDAT patients, 70% in the 2 nondemented PD patients and 40% in the 1 demented PD patient. The volume calculated for the compact part of the NbM formed by the CaBP i neuronal somata decreased by an average of 47% in SDAT. On the other hand, measurements in the volume of NGFr-i neurons (including the dendritic arborization) showed an average decrease of 25% in SDAT patients compared to controls. Although all SDAT and PD patients showed a decrease of CaBP-i neurons in the NbM, a loss of MAO-A-i NbM neurons was found only in those patients with dementia. Therefore, the relative proportions of MAO-A-i to CaBP-i neurons were increased in the nondemented PD patients (14.2 and 19.6%) when compared with those in the demented PD patient (2.2%) and with the SDAT patients (0.3-5.6%). These data indicate that a balanced presence of MAO-A-i cholinergic, large NbM neurons may be necessary for the proper maintenance of cognitive function. Functionally this may be translated to mean that dementing changes may cause a decrease from the normal amount of MAO A enzyme activity. This suggests that therapeutic strategies based upon correction of MAO-A activities by MAO-A inhibitors may be important to ameliorating some of the loss in cholinergic function in dementias of SDAT and PD. PMID- 8358502 TI - The spatial patterns of plaques and tangles in Alzheimer's disease do not support the 'cascade hypothesis'. AB - In Alzheimer's disease (AD), the 'Cascade hypothesis' proposes that the formation of paired helical filaments (PHF) may be casually linked to the deposition of beta/A4 protein. Hence, there should be a close spatial relationship between senile plaques and cellular neurofibrillary tangles in a local region of the brain. In tissue from 6 AD patients, plaques and tangles occurred in clusters and individual clusters were often regularly spaced along the cortical strip. However, the clusters of plaques and tangles were in phase in only 4/32 cortical tissues examined. Hence, the data were not consistent with the 'Cascade hypothesis' that beta/A4 and PHF are directly linked in AD. PMID- 8358503 TI - Brain damage caused by ischemia: pathophysiological and pharmacological aspects. AB - The distribution of brain cell injury after ischemic challenge is remarkable because only discrete brain areas are damaged, whereas other structures exhibit a very high resistance (selective neuronal death). The calcium hypothesis, one of the hypotheses that has been formulated to explain this selective vulnerability, postulates that an increase in excitatory amino acid release and the large calcium influx during ischemia leads to insufficient energy production and to stimulation of lipases, proteases, and endonucleases. This paper reviews the experimental data concerning the relationship between cerebral blood flow, glucose consumption and hippocampal morphological damage. The neuroprotective effects of some drugs against ischemic damage have also been discussed. PMID- 8358504 TI - Oral tetrahydroaminoacridine treatment of Alzheimer's disease evaluated clinically and by regional cerebral blood flow and EEG. AB - Neurochemical evidence indicates that cognitive impairment in dementia of Alzheimer type (DAT) is related to degeneration of cholinergic neurons in the brain. A pharmacological approach is treatment with a cholinesterase inhibitor such as tetrahydroaminoacridine (THA). THA treatment of 17 patients with DAT was studied with a double-blind crossover design with three types of treatment, THA + lecithin, THA + placebo and placebo + placebo. Each treatment period was 6 weeks with wash out periods of 2 weeks. The treatment was evaluated with clinical ratings, psychometric testing, EEG and regional cerebral blood flow (rCBF) measurements. No significant clinical differences between treatment periods were found in the total sample, but marked individual differences were observed. The patients were subdivided into three outcome groups based on four clinical measures: 6 patients improved (responders), 5 patients were mainly unchanged, and 6 patients showed further deterioration during the trial period of 26 weeks. Pretreatment rCBF in responders differed significantly from that of the deteriorated patients. EEG showed more high frequency activity among responders. Hepatotoxic side effects were observed in several cases. Three subjects showed marked increases of liver enzymes, with normalization following dose reduction. The majority of patients who improved or remained unchanged during the study chose to continue THA treatment in an open trial. PMID- 8358505 TI - Multichannel EEG frequency analysis and somatosensory-evoked potentials in patients with different types of organic dementia. AB - Thirty-five patients with organic dementia were investigated with multichannel FFT analysis of EEG. In 21 of them, somatosensory-evoked potentials (SEPs) with stimulation of the median nerves were also recorded. Based on clinical and psychometric data and regional cerebral blood flow measurements, the patients were subdivided into Alzheimer-type dementia (DAT) of moderate (n = 10) and severe (n = 11) degree, multi-infarct dementia (MID) (n = 7), and frontotemporal degeneration (FTD) (n = 7). The FTD patients showed mild EEG abnormality and the MID patients showed increases of low frequency activity in combination with a well-preserved posterior dominant activity. The DAT patients showed the most pronounced abnormalities with deterioration of the posterior activity combined with a large increase of low frequency activity. The SEPs of the DAT group showed an amplitude enhancement of the parietal response components. The FTD group showed only a moderate delay of the precentral N30 component. The MID group showed individually varying abnormalities, including a delay of the primary cortical response. It is concluded that the different distributions of pathology in the different organic dementia disorders are reflected in the quantified EEG and SEPs as studied with multichannel technique. PMID- 8358506 TI - Increased sweat sodium concentration in patients with Alzheimer's disease. AB - Sweat sodium concentration was estimated with pilocarpine iontophoresis in 15 women with Alzheimer's disease (AD) and 29 healthy control women. The age ranged from 76 to 96 years with a mean age of 85 years in both groups. The mean sodium concentration of 91 +/- 41 mmol/l (n = 11) in the Alzheimer patients was significantly higher than in the control group (62 +/- 29 mmol/l, n = 27, p = 0.0011). 27% of AD patients and 7% of the control women did not respond to stimulation. The impaired sweating in AD patients make them more vulnerable to heat stress. Further studies are needed to reveal whether the neurophysiological mechanism involved is located in the hypothalamus in cortical projections to the hypothalamus or in postganglionic sympathetic fibers. PMID- 8358507 TI - Psychometric discrimination of tetrahydroaminoacridine responders in Alzheimer patients. AB - Fourteen patients with probable Alzheimer's disease (AD) participated in an open tetrahydroaminoacridine (THA) treatment trial. Before initiation of THA treatment, a brief battery of neuropsychological tests was performed by an experienced neuropsychologist. The tests were repeated 120 min after a single dose of 50 mg THA had been administered perorally. Thereafter, the patients had a 4-week active treatment with THA 100 mg/day. After the treatment period, eight patients were defined as responders (increase of Mini-Mental State Examination score > or = 3) and six patients as nonresponders to the treatment. The responders showed significant improvement on Digit Span, Trail Making B, and on both Clock Setting and Clock Recognition tests after 50 mg of THA. The results suggest that in this subgroup of AD patients augmentation of the brain cholinergic systems mainly led to improvement of attentional and frontal-lobe rather than mnemonic functions. PMID- 8358508 TI - Clinical course and CSF amyloid beta protein precursor having the site of application of the protease inhibitor (APPI) levels in patients with dementia of the Alzheimer type. PMID- 8358509 TI - Is impaired recall in dementia of the Alzheimer type a consequence of a contextual retrieval deficit? AB - Eighty-eight patients with mild to moderate dementia of the Alzheimer type were tested in a word list and a spatial pattern recall task. With increasing degree of dementia severity we found a decline in the initial recall scores while learning curves over five consecutive trials remained normal in the mildly demented patients. Furthermore, there was a loss of the primacy effect in the word list task in our moderately demented patients. These findings are consistent with the pattern that have been reported after medial temporal lobe dysfunction. The data are discussed in the framework of cognitive dual process theories of memory as indicators of a contextual retrieval deficit. PMID- 8358510 TI - Long-term effects of bilateral frontal lobe lesions from neuropsychiatric and neuroradiological aspects. AB - Long-term effects of bilateral prefrontal lesions were studied in 14 lobotomized schizophrenic patients who were operated in the fifties. CT scans revealed cystic bilateral frontal lesions in almost every patient and cortical atrophy was seen in 5 patients. The prefrontal syndrome was severe in 1 patient, marked in 1 patient, mild in 9 patients and absent in 3 patients. Primitive reflexes could be elicited in 2 patients, 3 patients suffered from epileptic seizures, and 8 from minor motor defects. Four patients committed a homicide in the period after the operation, which indicates that the frequency of committing homicidal acts had doubled when compared with the situation before the operation. The incidence of homicides after lobotomy is extremely high considering that all patients except 1 were kept under continuous observation in hospitals. PMID- 8358511 TI - Delirium in the elderly: relationship of clinical symptoms to outcome. AB - Twenty-eight elderly patients meeting the DSM-III-R criteria for delirium were evaluated using the Delirium Rating Scale (DRS) in order to examine the relation between the clinical symptoms of delirium and its outcome. Patients whose delirious episode improved within 1 week had a significantly lower DRS score at the time of psychiatric consultation than patients whose delirium lasted more than 1 week. Neither the difference between the mean ages nor the sex distribution in the two groups was statistically significant. The present study suggests that the DRS is a valuable instrument for predicting the clinical outcome of delirium. PMID- 8358512 TI - Telephone-Assessed Mental State. AB - In 30 patients with Alzheimer's disease (AD), we compared performance on a brief Telephone-Assessed Mental State (TAMS) examination with performance on standard cognitive instruments administered face to face. TAMS scores correlated strongly with scores on both the Mini Mental State Examination (rho = 0.81) and the Alzheimer's Disease Assessment Scale (rho = -0.80). PMID- 8358513 TI - MRI findings in an individual at risk for familial Alzheimer's disease. PMID- 8358514 TI - Distribution of iron in the basal ganglia and neocortex in postmortem tissue in Parkinson's disease and Alzheimer's disease. AB - Post-mortem tissue was obtained from subjects with Parkinson's disease (PD), Alzheimer's disease (AD) and age-matched controls. Iron levels were measured from various sites of the basal ganglia and neocortex using atomic absorption spectrophotometry. The results indicate that iron levels are increased in the substantia nigra and the lateral segment of the globus pallidus of parkinsonian tissue. In contrast, the medial segment of the globus pallidus shows reduced iron levels in AD when compared to age-matched controls. No significant alterations of iron concentration were detected in AD in any region. These results are discussed in terms of the role of iron in the basal ganglia, mechanisms of abnormal deposition and possible neurotoxicity in PD. PMID- 8358515 TI - Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia. AB - It has remained a matter of debate until now whether amyloid and tangle pathology may be regarded as the main causes of the dementia in Alzheimer's disease (AD) or only as markers of the disease. In the present study we examined the synaptophysin immunoreactivity of the cortical neuropil as a measure of its synapse density, in 17 cases of AD, 1 case with a 10-month episode of dementia and cortical amyloid deposition, 5 cases of Huntington's disease (HD) with dementia, 11 cases of parkinsonism (PD), 5 with dementia (PD-D) and 16 controls. The immunoreactivity was assessed in two layers (molecular, pyramidal) of three regions (frontal, occipital, hippocampus) by means of automated black-and-white image analysis. In AD we found a rather diffuse reduction of the cortical synaptophysin expression of up to 26.5% (mean 11%) of the controls. No correlation was found between synaptophysin expressivity and age either in AD or in the controls. Univariate analyses revealed only a very weak negative correlation between the density of beta A4-immunoreactive cortical plaques and the intensity of the synaptophysin staining, while in a multivariate analysis the plaque density did not show any impact on the latter. In HD a reduction of the synaptophysin immunoreactivity of the cortical neuropil was also found (mean 10.4%), with a predominance in the pyramidal layer of the neocortex. The same was true for PD (5.3%) and PD-D (8.2%). Our results support the view that loss of synapses in the cortical neuropil may be a significant factor for the development of organic dementia, while the amyloid pathology in AD is more likely a marker of the disease. PMID- 8358516 TI - Rare neuropil threads in amyotrophic lateral sclerosis and parkinsonism-dementia on Guam and in the Kii Peninsula of Japan. AB - Using three different silver impregnation methods and antisera against microtubule-associated protein-tau (MAP-tau) and amyloid beta/A4 protein, we demonstrated abundant neurofibrillary tangles (NFTs), rare senile plaques, absence of amyloid angiopathy and rare MAP-tau- and silver-positive neuropil threads in the hippocampus of patients with amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) on Guam and in the Kii Peninsula of Japan. In contrast, abundant neuropil threads, NFTs, senile plaques with associated dystrophic neurites and amyloid angiopathy were confirmed in Alzheimer disease patients. These observations indicate that there may be important factor(s) responsible for the difference in the deposition and distribution of amyloid beta/A4 protein and MAP-tau between Pacific ALS and PD and Alzheimer disease. PMID- 8358517 TI - Assessment of depression in Alzheimer's disease: symptoms, syndrome, and computed tomography findings. AB - The Hamilton Rating Scale for Depression (HAM-D) and DSM-III-R criteria were simultaneously employed to assess the prevalence of depression in 26 outpatients with dementia of the Alzheimer type and 26 age-matched normal control subjects. Both assessment methods evidenced a higher frequency of depression during the severe stages of Alzheimer's disease. Among the Alzheimer patients, the prevalence rate of depression produced by the HAM-D (38%) was higher than the rate produced by DSM-III-R criteria (23%). Such a difference was due to the weight given by the HAM-D to the vegetative symptoms reported by the Alzheimer patients with more severe dementia. In a subgroup of 14 Alzheimer patients who underwent computed tomography, the volumetric measurement of CSF spaces did not reveal any difference between the depressed and nondepressed patients. On the basis of these results, the clinical problems related to the assessment of depression in Alzheimer's disease are discussed. PMID- 8358518 TI - Pattern of cerebral metabolic interactions in a subject with isolated amnesia at risk for Alzheimer's disease: a longitudinal evaluation. AB - A pattern of reduced cerebral metabolic rate for glucose (rCMRglc) has been shown by positron emission tomography (PET) in patients with dementia of the Alzheimer type. To verify if a similar rCMRglc pattern is present in subjects 'at risk' for Alzheimer's disease (AD), we used high-resolution PET to longitudinally study a subject with isolated memory impairment and a family history for autosomal dominant AD. Initial rCMRglc data did not reveal any consistent abnormality as compared to a group of sex- and age-matched healthy controls. However, 1 year later, a follow-up evaluation did reveal reduced parietal rCMRglc values coinciding with a worsening of cognitive impairment, which suggested that standard analyses of resting rCMRglc data may not be useful in the early diagnosis of AD. In contrast, when a previously determined discriminant function for distinguishing controls from AD patients was applied, the subject was correctly identified as an AD patient on both PET scans. PMID- 8358519 TI - Social support in labor--a selective review. AB - Support during labor has been offered by a variety of different people, including fathers, professional medical staff, trained labor coaches and monitrices, untrained lay supporters and family and friends. A comparison of the various findings shows that support given by trained or lay untrained female supporters, who are not necessarily known to the laboring woman, yields the most extensive, methodologically sound, and consistently positive effects on obstetric and psychosocial outcomes. Although trained labor coaches have been shown to exert a positive effect on outcome, the results of doula support are the most impressive when both methodology and outcome effects are considered. Studies of father support have yielded contradictory findings, although women do appear to value their presence in most studies. Family and friends have not been shown to influence outcomes. Support from professional medical staff is rare, but when given, has, in some cases, had a positive effect. These findings are important for the field, since the use of lay supporters constitutes a low-cost preventive intervention. The inclusion of lay supportive women is also consistent with traditional practices in most countries in the world. PMID- 8358520 TI - The potential value of a short self-completion questionnaire for the assessment of habitual physical activity in pregnancy. AB - The aim of this methodological study was to validate a newly designed self completion questionnaire assessing various dimensions of physical activity among 100 pregnant women in Bristol, UK. For this purpose different measures obtained by self-completion questionnaire were compared with those simultaneously obtained by two established assessment methods for physical exertion. Based on the findings it was suggested that the self-completion questionnaire be slightly modified by adding questions pertaining to household activities and deleting questions which proved to be conceptually meaningless. It is concluded that in future studies this strategy will facilitate the understanding of the complex relationship between way of life and pregnancy outcome. PMID- 8358521 TI - The relationship between sex role and emotional functioning in patients undergoing assisted conception. AB - It is suggested that infertility may be distressing because it results in an inability to fulfil traditional roles and thus those individuals who adhere to traditional sex roles may be more distressed by the experience of infertility. In order to examine the relationship between sex role and emotional well-being in infertility patients, 58 women attending a clinic for assisted conception procedures and 31 of their male partners completed questionnaires assessing sex role type (i.e. masculine, feminine, androgynous or undifferentiated) and emotional, marital and sexual functioning. Women with a traditional feminine sex role type were more anxious than those with a masculine sex-role type but there were no differences in depression or marital or sexual functioning. Men with an undifferentiated sex-role type were more anxious and depressed than those with other sex-role types. The findings are discussed in terms of the relationship between sex role and infertility, previous research into sex differences in distress amongst infertility patients, and the problems associated with measuring distress. PMID- 8358522 TI - Premenstrual symptoms and dysmenorrhea in relation to emotional distress factors in adolescents. AB - The extent to which premenstrual symptoms occur when they are distinguished from primary dysmenorrhea and the relationship of premenstrual symptoms to other emotional distress in adolescents is not well understood. This pilot investigation examined relationships between premenstrual symptoms, dysmenorrhea and emotional distress factors in a sample of 165 females, ages 15-19 years. Premenstrual symptoms were correlated with dysmenorrhea (r = 0.54, p < 0.0001). Subjects with premenstrual symptoms had significantly more emotional distress than the normal group as assessed by the Symptom Checklist (SCL-90), an objective self-report questionnaire. In contrast, dysmenorrhea had no relationship with the SCL factors and no interaction with premenstrual symptoms in relation to emotional distress. The SCL scores significantly decreased from baseline (2 years earlier) in the normal group but not in the premenstrual symptom group. The data show that premenstrual symptoms were associated with other emotional distress factors in adolescents while dysmenorrhea was not. A further prospective, longitudinal study of menstrually-related symptoms in adolescents is needed to learn about the development of these premenstrual symptoms that may be related to the premenstrual syndrome seen clinically in the later reproductive years. PMID- 8358523 TI - Changes in sexual behavior following radiation therapy for cervical cancer. AB - Twenty-one women with cervical cancer Types I and II, treated by radiation were evaluated by comparing periods before cancer and after therapy in order to identify changes in sexual behavior; if so, whether they attributed the changes to therapy, or whether other factors were associated with being sexually dysfunctional or non-dysfunctional. Data were obtained through administration of a sexual behavior questionnaire, personal interviews and review of medical records. Statistically significant changes were found: decreased frequency of masturbation and intercourse, decreased frequency of orgasm through non-coital sexual activities, less satisfaction with sex, and less enjoyment of intercourse. The majority believed that changes were due to radiation therapy and reflected decreased feelings of self-esteem, sex desirability and attractiveness. Most of the women believed that cancer could be transmitted through intercourse. Women who did not follow advice regarding use of vaginal dilators and did not resume their pre-illness level of sex were more likely to develop physical and sexual changes. The subjects' need for sexual counselling concerning the effect of the illness and treatment on relationships with partners was strongly evident. Suggestions for preventing undesirable physical and psychological changes, and guidelines for counselling are provided. PMID- 8358524 TI - Evolution of maternal mood state and of the auditory and olfactory perception of their newborn: preliminary data. AB - The auditory and olfactory discrimination ability of mothers, in relation to stimuli from their newborn infants, was concomitantly measured in a sample of 12 mother-newborn dyads during the 1st week after the child's birth. Both types of discrimination ability had a parallel evolution from one day to the next. The performances continued to increase from day to day, except on the 4th and 7th days. These 2 days corresponded to times when the mothers were more depressed. Half of the mothers were more skilled in one sensorial skill than the other. PMID- 8358525 TI - Comparative prospective study of the psychological development of children born by in vitro fertilization and their mothers. AB - A comparative prospective survey of psychomotor development and mother-infant bonding was conducted on 33 children born after in vitro fertilization and two control groups composed of: a group of children born to infertile women who underwent ovulation induction treatment but with no medically assisted procreation; and a group of children born by natural procreation, with no medical intervention. No major disorders were observed. In the postpartum, the minor mother-infant relational problems seemed to be more frequent in the in vitro fertilization and infertility groups but with no statistical differences. At 9 months, the factors related to sleep disturbances in the child and maternal depressive syndromes seemed to be more frequent in the in vitro fertilization and infertility groups than in the controls. At 18 months these minor disturbances decreased and there were fewer differences across the three groups. This trend was confirmed at 3 years. PMID- 8358526 TI - The climacteric and well-being. AB - The climacteric is accompanied by many changes in life, which may give cause to a variety of complaints. Thus, it may be difficult to discern to what extent the climacteric is related to well-being. The association between menopausal status and well-being was determined in a population of 2729 women aged 45-60 years. A self-administered questionnaire was filled out and returned by 1947 women (response 71.3%). Well-being was measured by the Inventory of Subjective Health (ISH) and the three subscales of the Sickness Impact Profile (SIP): social functioning; emotions, feelings and sensations; and intellectual functioning. The relationship between menopausal status and well-being was estimated using linear regression analysis, while adjusting for age and other potential confounding variables, including body mass index, smoking behavior, education, work outside the home, parity, way of cohabitation, difference in age with the partner and partner's employment. The results show that early perimenopausal women report a lower level of well-being as compared to premenopausal women on all three SIP scales. Early postmenopausal women report a lower level of well-being on the SIP emotions, feelings and sensations. Intermediate postmenopausal women have a lower level of well-being on the ISH only. Finally, late postmenopausal women have a lower level of well-being on the SIP social functioning and SIP emotions, feelings and sensations. We tentatively conclude that the influence of the climacteric on well-being independent of confounders is primarily found in behavioral functioning in the daily life of a woman. PMID- 8358527 TI - Psychological aspects of genital human papillomavirus infection: a preliminary report. AB - Genital human papillomavirus (HPV) infection can lead to self-inflicted blame and hypochondriac fears as well as to problems with sexuality. The aim of this study was to assess the psychological and psychodynamic aspects of patients with widespread genital HPV infection entering into a clinical trial in which they were randomly assigned to three treatment groups: CO2 laser ablation, intramuscular interferon-alpha, CO2 laser ablation plus intramuscular interferon alpha. Fifty-one patients were studied. Patients were asked to take a series of questionnaires which included a self-rating questionnaire for gathering information on sexuality, emotional relationship with the partner and social life. A visual analog scale was used to rate intensity of pain during sexual intercourse. Each patient went also through an in-depth interview with a clinical psychologist and filled out two personality tests to measure depression (CDQ = IPAT depression test) and anxiety (ASQ = IPAT anxiety test). Results indicated a high percentage of sexual impairments after therapy (28 cases), presence of fear of cancer (14 cases) and worsenings in the emotional relationship with the partner. No difference was found among groups of treatment. PMID- 8358528 TI - Maternal-fetal attachment during pregnancy following in vitro fertilization. AB - The aim of the study was to examine the degree of anxiety experienced by pregnant women who had conceived by in vitro fertilization (IVF), as well as their attitudes towards the pregnancy and the strength of their attachment to the fetus. Fifteen women who had conceived by IVF were compared with 20 women who had conceived without assistance. Each woman was administered the State-Trait Anxiety Inventory, the Childbearing Attitudes Questionnaire and the Maternal-Fetal Attachment Scale. While the two groups of expectant mothers did not differ on these measures, a clear relationship was found for all of the women combined between general attitudes towards childbearing and attachment to the fetus, showing that women who are less positive about pregnancy, childbirth and childcare show weaker attachment to their unborn child. PMID- 8358529 TI - Neuropsychiatric aspects of Sydenham's chorea: a case report. AB - A case report of a 21-year-old girl developing Sydenham's chorea in pregnancy following a probable streptococcal A infection is reported. Associated neuropsychiatric aspects are discussed. Awareness of this condition is encouraged to prevent possible misdiagnosis. PMID- 8358530 TI - Is premenstrual syndrome an endocrine disorder? AB - To both patients and physicians it seems natural to attribute adverse premenstrual phenomena to cyclic fluctuations of hormones produced by the ovary. This seems so plausible that, although the endocrine mechanism that causes premenstrual syndrome remains unknown, the condition itself is often treated with hormonal substances. Psychosocial factors are thus considered to be of only secondary importance. They may play a role as a contributing factor, to the 'real' cause of premenstrual syndrome they are not an essential ingredient. The aim of this review article is to examine how strong the evidence is for the possible existence of an endocrine factor as the causative agent in premenstrual syndrome. Using an epidemiological approach we conclude that the continuing search for the responsible mechanism that causes premenstrual syndrome may very well be an endocrine 'Holy Grail'. Human behavior cannot be understood within a single (hormonal) frame of reference. Cyclical ovarian activity is only one of the etiological factors in premenstrual syndrome. Unravelling the pathogenesis of premenstrual syndrome requires a multidisciplinary approach. PMID- 8358531 TI - Peripheral endotoxin induces hypothalamic immunoreactive interleukin-1 beta in the rat. AB - Interleukin-1 (IL-1) is a polypeptide produced by a variety of cells and contributes to the general host response to inflammation. It displays a wide spectrum of inflammatory, metabolic, physiological, haematopoietic and immunological activities. Brain cells, including neurones, microglia, endothelial cells and astrocytes can all produce IL-1 beta in response to various physiological and pathological stimuli. In this report we show that peripherally administered endotoxin stimulates the appearance of immunoreactive IL-1 beta (IL 1 beta) in the rat hypothalamus as measured by an ultrasensitive, highly specific enzyme amplified immunometric assay for rat IL-1 beta. PMID- 8358532 TI - Mg2+ and caffeine-induced intracellular Ca2+ release in human vascular endothelial cells. AB - Interaction of ionized magnesium ([Mg2+]o) and caffeine in regulation of intracellular free calcium concentration ([Ca2+]i) in human aortic endothelial cells was studied using fura-2 and digital imaging microscopy. In 1.2 mM [Mg2+]o, basal [Ca2+]i was 73.7 +/- 22.4 nM, with a heterogeneous distribution within the cells. No significant changes of basal [Ca2+]i were found either when cells were treated with 10 mM caffeine or when [Mg2+]o was lowered from 1.2 mM to 0.3 mM. However, a combined superfusion of the cells with 0.3 mM [Mg2+]o and 10 mM caffeine resulted in a significant elevation of [Ca2+]i to 382.8 +/- 57.1 nM, probably by release of Ca2+ from internal stores, which was attenuated by NiCl2 (1 mM). These results suggest that a Ca(2+)-induced Ca2+ release mechanism is involved in regulation of [Ca2+]i in endothelial cells, which may be either regulated or modulated by Mg2+. PMID- 8358533 TI - Differential effects of cocaine and cocaethylene on intracellular Ca2+ and myocardial contraction in cardiac myocytes. AB - 1. Isolated cardiac myocytes of the ferret were used to investigate the influence of cocaine and cocaethylene on the intracellular Ca2+ transient indicated by the indo-1 405/480 nm ratio signal, and peak cell shortening. 2. Both cocaine and cocaethylene produced significant decreases in peak intracellular Ca2+ and peak cell shortening in a dose-dependent manner. Of interest, (1) the minimally effective dose of cocaethylene was ten fold lower (10(-8)M versus 10(-7)M) than that of cocaine; (2) the log EC50 of cocaethylene was -5.99 +/- 0.13 (1.0 x 10( 6) M), which was about ten fold lower than that of cocaine (-5.02 +/- 0.11, 9.6 x 10(-6) M); and (3) 1 x 10(-4)M cocaethylene decreased the contraction amplitude by 71 +/- 7%, while the same concentration of cocaine decreased the amplitude only by 55 +/- 5%, indicating that cocaethylene is more potent than cocaine. 3. The negative inotropic effects of either cocaine or cocaethylene could be overcome by noradrenaline (approximately 5 microM) or calcium. 4. In contrast to cocaine, cocaethylene shifted the peak [Ca2+]i-peak shortening relationship downward, indicating that cocaethylene decreased myofilament Ca(2+) responsiveness. 5. These data indicate that both cocaine and cocaethylene act directly on cardiac myocytes to produce a negative inotropic effect that is due to decreased Ca2+ availability. In contrast to cocaine, cocaethylene produces more potent inhibition by an additional action to decrease myofilament Ca(2+) responsiveness. PMID- 8358534 TI - High-affinity uptake of noradrenaline in postsynaptic neurones. AB - 1. Neurotransmitters released from nerve endings are inactivated by re-uptake into the presynaptic nerve terminals and possibly into neighbouring glial cells. While analysing the functional properties of alpha 1-adrenoceptors in the hypothalamus, we observed a high-affinity uptake process for noradrenaline in postsynaptic peptidergic neurones. 2. In primary hypothalamic cell cultures and in a hypothalamic neuronal cell line, [3H]-prazosin bound with high affinity and was displaced by unlabelled prazosin in concentrations of 10(-10) to 10(-7) M. However, at concentrations of unlabelled prazosin above 10(-7) M, there was a paradoxical increase in apparent [3H]-prazosin binding. 3. Methoxamine, an alpha 1-adrenoceptor ligand that is not subject to significant neuronal uptake, displaced [3H]-prazosin but did not cause the paradoxical increase in the apparent binding of [3H]-prazosin. Cooling the cells to 4 degrees C reduced the total amount of prazosin associated with the cells; under these conditions, methoxamine almost completely inhibited [3H]-prazosin binding to the cells. 4. In the presence of desipramine (DMI), unlabelled prazosin displaced [3H]-prazosin as before, but no paradoxical increase in apparent binding was seen above 10(-7) M. 5. The paradoxical increase of [3H]-prazosin binding was not observed in membrane preparations of hypothalamic neurones. These findings indicated that the paradoxical increase in apparent [3H]-prazosin binding was due to a cellular uptake process that becomes evident at high concentrations of the ligand. 6. DMI (10(-5) M) had no effect on the specific binding of [3H]-prazosin. The presence of alpha1-adrenoceptors was confirmed by binding of [125]-HEAT, but [3H]-idazoxan (an alpha2- ligand) did not bind to the cells.7. The uptake of prazosin obeyed the Michaelis-Menten model, with similar Km and Vmax values in both types of cultures.8. Noradrenaline was taken up with high affinity by both types of cultures. (+/-)-[3H]-noradrenaline uptake was reduced by DMI and by excluding sodium from the medium, indicating that this process has some of the properties of uptake 1. (+/-)-[3H]-noradrenaline uptake in the cell line was unaffected by testosterone.9. The measured uptake of (-)-noradrenaline in the cell line was considerably increased by blockade of catechol-omicron-methyl-transferase and monoamine oxidase, suggesting that (-)-noradrenaline is metabolized to lipophilic products that escape across the plasma membrane.10. Studies in rats, in which the noradrenaline isomer 6-hydroxydopamine was used, suggested that the post synaptic uptake process is operative in hypothalamic CRH and vasopressin neurones in vivo.11. The Km for (-)-noradrenaline was within the range for the high affinity uptake, process in noradrenergic neurones. Uptake takes place in concentrations at which noradrenaline activates alpha1-adrenoceptors.Removal of noradrenaline from the vicinity of the receptors may prevent desensitization,thus maintaining the responsiveness of postsynaptic neurones to the actions of the neurotransmitter. PMID- 8358535 TI - Effects of potassium channel openers and their antagonists on rat locus coeruleus neurones. AB - 1. Intracellular recordings were obtained from a pontine slice preparation of the rat brain containing the locus coeruleus (LC). Two openers of ATP-sensitive potassium (K(ATP)) channels, RO 31-6930 (10 microM) and cromakalim (100 microM) decreased the spontaneous discharge of action potentials without altering their amplitude or duration. Neither compound changed the resting membrane potential. 2. Of two K(ATP) channel blockers, tolbutamide (300 microM) increased the firing rate, while glibenclamide (3 microM) only tended to do so. In addition, both compounds antagonized the effect of RO 31-6930 (10 microM). Neither glibenclamide (3 microM) nor tolbutamide (300 microM) altered the resting membrane potential. 3. Tetrodotoxin (0.5 microM) depressed the firing, but did not influence the inhibitory action of RO 31-6930 (10 microM). The excitatory amino acid antagonist, kynurenic acid (500 microM), did not change the spontaneous discharge of action potentials. 4. Small shifts (2-4 mV) of the membrane potential by hyper or depolarizing current injections markedly decreased and increased the firing rate, respectively. 5. Noradrenaline (100 microM) hyperpolarized the cells and decreased their input resistance. This effect was not antagonized by glibenclamide (3 microM) or tolbutamide (300 microM). Ba2+ (2 mM), a blocker of both ATP-sensitive and inwardly rectifying potassium channels, abolished the effects of RO 31-6930 (10 microM) and noradrenaline (100 microM). 6. These data suggest that K(ATP) channels are present on the noradrenergic LC neurones, but are not coupled to alpha 2-adrenoceptors. PMID- 8358536 TI - Inhibition by the adenosine analogue, (R-)-N6-phenylisopropyladenosine, of kainic acid neurotoxicity in rat hippocampus after systemic administration. AB - 1. Binding of the peripheral benzodiazepine receptor ligand, [3H]-PK 11195, to rat hippocampal membranes has been used to quantify the reactive gliosis resulting from neuronal death induced by intraperitoneally administered kainic acid. 2. Intraperitoneal administration of kainic acid (10 mg kg-1) caused a 350 500% increase in [3H]-PK 11195 binding measured in rat hippocampal P2 membranes 7 days later. Co-treatment with the adenosine derivative R-phenylisopropyladenosine (R-PIA) (100, 25 or 10 micrograms kg-1, i.p.) abolished this elevation. The protective action of R-PIA could itself be abolished by co-treatment with 8 phenyltheophylline (1 mg kg-1). 3. Body temperatures were recorded in the antagonist experiments and no significant changes were recorded, suggesting that the protective action of R-PIA was not mediated by hypothermia. 4. Since systemic kainic acid-induced neurotoxicity has been claimed as a good model of neuronal death in temporal lobe epilepsy, the results suggest that the systemic administration of purines in low doses may provide protection against certain neurodegenerative insults. PMID- 8358538 TI - Novel regulation of muscarinic receptors and their coupling with G proteins in smooth muscle: transient resensitization during desensitizing process. AB - 1. Muscarinic stimulation of the smooth muscle of guinea-pig taenia caeci was produced with 10(-4) M carbachol for 15 s, 30 s, 1 min, 2 min and 30 min, and the time course of developing desensitization was studied by measuring the muscle contractility and the binding characteristics of muscarinic receptors. 2. The contractile response to carbachol was analyzed using dose-response curves. The response to 10(-7) M carbachol was reduced by treatment for 15 s with 10(-4) M carbachol (fast desensitization), but recovered partially after 30 s treatment and completely after 1 min treatment (resensitization). Contractility was reduced again after 2 min and 30 min treatment (re-desensitization). 3. The affinity of carbachol for muscarinic receptors was changed by the carbachol treatment in a manner similar to the contractility. Thus, the affinity was reduced at 15 s, restored slightly at 30 s and completely at 1 and 2 min, and was reduced again at 30 min. 4. 5'-Guanylylimidodiphosphate (GppNHp), a non-hydrolysable analogue of guanosine triphosphate (GTP) reduced the affinity of muscarinic receptors for carbachol via guanine nucleotide-binding regulatory proteins (G proteins). A similar effect was observed in tissues desensitized by 15 s carbachol treatment. This effect disappeared after 30 s, recovered completely after 1 and 2 min, and disappeared again after 30 min carbachol treatment. 5. Neither the dissociation constant (Kd value) nor the maximal binding (Bmax) of [3H]-quinuclidinyl benzilate ([3H]-QNB) to muscarinic receptors were changed by the carbachol treatment. 6. These results indicate that the whole process of desensitization, resensitization and re-desensitization are related to changes in the binding ability of muscarinic receptors, in their coupling with G proteins and in the post-receptor steps of the signal transduction. We emphasize that the desensitizing process involves an early transient phase of resensitization that could be caused by restoration of both the affinity of carbachol for muscarinic receptors and their coupling with G proteins. This novel resensitization mechanism may have some physiological significance for cellular homoeostasis by modulating cellular responsiveness transiently or even in an oscillatory manner during the process of desensitization. PMID- 8358537 TI - Mechanisms of vasodilatation in pregnancy: studies of the role of prostaglandins and nitric-oxide in changes of vascular reactivity in the in situ blood perfused mesentery of pregnant rats. AB - 1. To examine the possible mechanisms of the vasodilatation and blunted pressor responses in late pregnancy, we have studied vascular reactivity of the in situ blood perfused mesenteric resistance vessels of 18-20 day pregnant Wistar-Kyoto rats (WKY). 2. Intra-arterial mean blood pressure (MBP) was lower in pregnant rats than in nonpregnant controls. There was no significant difference in basal mesenteric perfusion pressure (BPP) between groups. 3. Vascular reactivity to electrical stimulation (ES) or intra-arterial noradrenaline (NA), angiotensin II (AII) and arginine vasopressin (AVP) was decreased in the preparations from pregnant rats compared to that from nonpregnant controls. Noradrenaline spillover into mesenteric venous blood following ES was similar in pregnant and nonpregnant animals. 4. Indomethacin (5 mg kg-1, i.v.), an inhibitor of cyclo-oxygenase, induced significant increases in reactivity to ES in both pregnant and nonpregnant groups while potentiating the responses to NA and AII in nonpregnant animals only and having no effect on AVP-induced contractions in the preparations from either pregnant or nonpregnant animals. 5. NG-nitro-L-arginine (L-NOARG) (5 mg kg-1, i.v.), an inhibitor of nitric-oxide synthase, increased MBP and BPP in both pregnant and nonpregnant animals, but the difference in MBP between groups was still evident. 6. L-NOARG enhanced mesenteric vascular responses to ES, NA and AII in both pregnant and nonpregnant groups. Only the difference in NA responses between groups was abolished after pretreatment with L-NOARG. 7. These data show that vasoconstrictor responses to a variety of agonists are decreased in the in situ blood-perfused mesenteric resistance vessels of pregnant rats. Increase in endothelial-dependent nitric oxide generation could contribute to the vasodilatation seen in pregnancy but other mechanisms might also be involved. Cyclo-oxygenase products are not responsible for any decreased contractile responses in this preparation. PMID- 8358539 TI - The superficial buffer barrier in venous smooth muscle: sarcoplasmic reticulum refilling and unloading. AB - 1. The interaction of Ca2+ transport in the plasmalemma and the sarcoplasmic reticulum (SR) was investigated in smooth muscle of the rabbit inferior vena cava. We tested the possibility of direct refilling of the SR with extracellular Ca2+ and of the existence of a vectorial Ca2+ extrusion pathway from the SR lumen to the extracellular space suggested by earlier results. 2. After depletion with caffeine the SR was loaded with Ca2+ to increasing levels by incubation in a high potassium 1.5 mM Ca2+ solution and a 10 mM Ca2+ zero Na+ solution, respectively. Thapsigargin, 2 microM, (a specific SR Ca(2+)-ATPase blocker) completely blocked refilling of the SR in either of the above solutions, indicating that the SR Ca(2+)-ATPase is essential for this process. 3. Three different agents, caffeine, ryanodine and thapsigargin, which inhibit Ca2+ accumulation by the SR, increased the steady state intracellular Ca2+ concentration in the rabbit inferior vena cava. 4. Measurements of Mn2+ induced quenching of the intracellular fura-2 signal during pharmacological manipulation of the SR content showed that these three agents did not stimulate divalent cation entry. 5. On the other hand, stimulation with noradrenaline caused a marked increase in Mn2+ influx, which was blocked by 2 mM Ni2+. Mn2+ entry stimulated by high K+ solution was blocked by 1 microM diltiazem. 6. We conclude that the SR refilling has to be mediated by the SR Ca(2+)-ATPase. Inhibition of Ca2+ accumulation by the SR causes an increase in the steady state intracellular Ca2+ concentration. This observation cannot be explained by an increase in Ca2+ influx into the smooth muscle cells of the rabbit inferior vena cava. Alternatively these results suggest the existence of a continuous vectorial release of Ca2+ from the SR lumen to the extracellular space. PMID- 8358540 TI - Desensitization of histamine H1 receptor-mediated inositol phosphate production in HeLa cells. AB - 1. Histamine stimulated the accumulation of total [3H]-inositol phosphates (IPn) in control HeLa cells with an EC50 of 3.7 +/- 0.7 microM in the presence of 10 mM LiCl. The maximum response to histamine after 15 min incubation was 43 +/- 5% over basal accumulation and occurred at a concentration of 1 mM histamine. 2. The histamine-induced IPn production in HeLa cells was confirmed as H1 receptor mediated, since the H1 antagonist mepyramine (10(-6) M) inhibited the histamine response (10(-4) M) by 83 +/- 7%, whereas the H2 antagonist, ranitidine (10(-4) M), and H3 antagonist, thioperamide (10(-6) M), were ineffective. 3. Histamine (10(-4) M) pretreatment of HeLa cells for 30 min desensitized the subsequent histamine-induced IPn accumulation. The desensitized cells accumulated IPn in response to histamine with an EC50 of 1.7 +/- 0.7 microM after 15 min incubation. The maximum histamine-induced IPn accumulation at 10(-4) M was 19 +/- 5% over basal and was significantly lower (P < 0.03) than the maximum response in control cells. 4. The desensitization of histamine-induced IPn accumulation was time dependent and, at a desensitizing histamine concentration of 10(-4) M, the half maximal attenuation occurred after approximately 9 min and maximum desensitization was achieved by 15-20 min. The desensitization of the IPn accumulation was a reversible phenomenon and full recovery of the response occurred 150 min after the removal of the desensitizing histamine-containing medium. The half-time for the recovery of the histamine-induced response was estimated at 120 min. 5. Bradykinin stimulated IPn, accumulation in HeLa cells, and the ECm in control cells of 1.9 +/- 0.2 nM was not significantly different from the EC50 value from histamine-pretreated cells of 1.6 +/- 0.9 nM. The bradykinin response at 1 microM was 194 +/- 48% over basal IPn accumulation in control cells and this value was significantly different (P <0.04) from the 1 microM bradykinin-induced IPn accumulation in histamine pretreated HeLa cells of 143 +/- 38% over basal.6. NaF stimulated IP,, accumulation in control HeLa cells in a dose-related manner, with the maximum effect occurring at 15-20 mM. The EC50 value for NaF-stimulated IPn accumulation in control cells was 10.5 +/- 1.1 mm and the maximum response was 136 +/- 41% over basal after 20 min incubation. In histamine desensitized HeLa cells the EC50 value for NaF was 12.3 +/- 0.4 mM after 20 min stimulation,which was not significantly different from the value obtained in control cells. The maximum NaF stimulated IPn formation in desensitized cells of 68 +/- 23% over basal occurred at 15 -20 mM and was significantly lower (P<0.01) than that obtained in control cells.7. We show here that the acute histamine pretreatment of HeLa cells results in the desensitization of histamine H1 receptor-mediated IPn production. The desensitization was not restricted to the H1 receptor-mediated signal transduction pathway, but also includes both the bradykinin- and NaF mediated responses, supporting a heterologous desensitization mechanism. Our results are consistent with the site of attenuation being at or distal to the G-protein and the underlying mechanism being a slowed time-course for the production of inositol phosphates. PMID- 8358541 TI - Modulation of vasodilatation to levcromakalim by hypoxia and EDRF in the rabbit isolated ear: a comparison with pinacidil, sodium nitroprusside and verapamil. AB - 1. We have used an isolated buffer-perfused preparation of the rabbit ear to investigate the effects of hypoxia and inhibition of endothelium-derived relaxing factor (EDRF) synthesis on the vasodilator responses to the potassium channel opener, levcromakalim (the active (-)-enantiomer of cromakalim). The results obtained with levcromakalim have been compared with those for pinacidil, sodium nitroprusside and verapamil. 2. Levcromakalim relaxed preconstricted preparations with an EC50 = 343 +/- 41 nM and Rmax = 80.3 +/- 6.4%. Under hypoxic conditions the concentration-response curve was significantly (P < 0.01) shifted to the left with an EC50 = 118 +/- 16 nM and Rmax = 89.9 +/- 2.7%. Hypoxia did not influence relaxation to either pinacidil, sodium nitroprusside or verapamil. 3. Inhibition of EDRF synthesis with 100 microM NG-nitro-L-arginine methyl ester (L-NAME) also significantly (P < 0.001) increased the vasodilator potency of levcromakalim (EC50 = 56 +/- 5 nM), and caused a similar shift in the concentration-response curve to sodium nitroprusside. It did not influence vasodilation to either verapamil or pinacidil. The potentiation of vasodilator responses to levcromakalim by L-NAME was reversed by an excess of L-arginine. 4. Impairment of oxidative phosphorylation with 400 nM carbonyl cyanide m-chlorophenylhydrazone significantly (P < 0.05) increased the potency of levcromakalim (EC50 = 120 +/- 20 nM) but did not influence vasodilation to pinacidil or endothelium-dependent relaxations to acetylcholine. 5. Vasodilatation to levcromakalim was augmented both by hypoxia and by inhibition of EDRF activity. Since impairment of oxidative phosphorylation increased the potency of levcromakalim but did not alter EDRF activity then the mechanism responsible for hypoxic facilitation of responses to levcromakalim is likely to be due to reduced ATP levels in hypoxic smooth muscle cells rather than a change in EDRF activity. These results suggest that levcromakalim may selectively dilate both hypoxic vessels and vessels with impaired EDRF activity. The results also point to important differences in the pharmacology of levcromakalim and pinacidil. PMID- 8358542 TI - Interaction between the effects of 5-hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog. AB - 1. The interaction between adrenaline and 5-hydroxytryptamine (5-HT) has been quantitated on the rate of thrombus formation, in the stenosed coronary artery with damaged endothelium of the anaesthetized dog. 2. Changes in the plasma concentration of adrenaline were produced by varying the rate of an intravenous infusion of adrenaline and in the effects of 5-HT, by intravenous injections of the selective 5-HT2 receptor antagonist, ICI 170809. 3. Increases in the plasma concentration of adrenaline, which did not cause significant changes in blood pressure and heart rate, increased the rate of thrombus formation. 4. Antagonism of the 5-HT2 receptor by ICI 170809, in the absence of an infusion of adrenaline, abolished thrombus formation (mean ED50 0.41 microgram kg-1, i.v.). 5. The effects of adrenaline were non-competitively antagonized by ICI 170809; maximum effects were obtained in the dose-range 50-200 micrograms kg-1, i.v., when the mean dose-ratio increase in adrenaline required to restore equivalent rates of thrombus formation was 39 fold. 6. These results are consistent with a synergism between adrenaline and 5-HT and emphasize the importance of both on thrombus formation. PMID- 8358543 TI - A2-purinoceptor-mediated relaxation in the guinea-pig coronary vasculature: a role for nitric oxide. AB - 1. The Langendorff heart preparation was used to investigate the mechanism of action of the endothelium-dependent vasodilatation evoked by adenosine and its analogues in the guinea-pig coronary vasculature. 2. The relative order of potency of adenosine and its analogues in causing a reduction in perfusion pressure was D-5'-(N-ethylcarboxamide)adenosine (NECA) = 2-[p-(2 carboxyethyl)phenylethylamino]-5'-N- ethylcarboxamidoadenosine (CGS 21680)> R-N6 (2-phenylisopropyl)adenosine (R-PIA) = adenosine = 2-chloroadenosine (2-CA) > S N6-(2-phenylisopropyl)adenosine (S-PIA) = N6-cyclopentyl-adenosine (CPA); thus suggesting the presence of A2-purinoceptors in this preparation. 3. 8-(p Sulphophenyl)theophylline (8-PSPT; 3 x 10(-5) M) significantly reduced both the maximum amplitude and area of the vasodilatation produced in response to adenosine (5 x 10(-10) -5 x 10(-8) mol) without having any effect on the response to the P2-purinoceptor agonist, 2-methylthioATP. The relaxation induced by adenosine (5 x 10(-12) -5 x 10(-8) mol) was unaffected by the selective A1 purinoceptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10(-8) M). This antagonist profile suggests that only A2-purinoceptors are present in the guinea-pig coronary vasculature. 4. The areas of the vasodilator response to adenosine (5 x 10(-10) -5 x 10(-7 mol), NECA (5 x 10(-12) -5 x 10(-7) mol) and CGS 21680 (5 x 10(-12) -5 x 10(-10) mol) were significantly reduced by NG-nitro-L arginine methyl ester (L-NAME; 3 x 10(-5) M). The amplitude of the responses to low concentrations of adenosine (5 x 10-10-5 x 10-9mol), NECA (5 x 1011 mol) and CGS 21680 (5 x 1011-5 x 10-9mol)were significantly reduced by L-NAME (3 x 10-5 M).5. L-Arginine (1.5 x 10-3 M) significantly reversed the inhibition, by L-NAME (3 x 10-5 M), of the relaxant response to adenosine (5 x 10-8 mol), NECA (5 x I0- mol) and CGS 21680 (5 x 10-11 mol).6. Indomethacin (10-6 M) did not inhibit the response to adenosine, except at low doses (5 x 10-11-5 x 10-10 mol).7. It is concluded that in the guinea-pig coronary vasculature, while a major part of the vasodilator action of adenosine is probably directly via A2-receptors on the smooth muscle, activation of a subpopulation of A2-purinoceptors on endothelial cells by adenosine and its analogues induces relaxation via production of nitric oxide; prostanoids appear to play a minimal role in the relaxation induced by adenosine as in most other preparations. PMID- 8358544 TI - Release of nitric oxide from glyceryl trinitrate by captopril but not enalaprilat: in vitro and in vivo studies. AB - 1. The hypotensive effects of glyceryl trinitrate (GTN, 0.5 mg kg-1) but not of 3 morpholino-sydnonimine (SIN-1, 0.125 mg kg-1) in anaesthetized rats were attenuated following a seven day (using a q.i.d. dosing schedule) oral treatment with isosorbide-5-mononitrate (IS-5-MN; 5 mg kg-1) indicative of the induction of tolerance to GTN but not to SIN-1. The hypotensive effects of GTN did not decline when the sulphydryl (SH) containing angiotensin converting enzyme inhibitor (ACE 1), captopril (CPT, 5 mg kg-1) or the structurally unrelated SH-containing, N acetylcysteine (NAC, 10 mg kg-1) but not the non-SH-containing ACE-I, enalaprilat (ENA, 5 mg kg-1) were given together with IS-5-MN for the seven days treatment. 2. The attenuated hypotensive effects of GTN (0.5 mg kg-1) in rats treated with IS-5-MN were also restored when CPT (1 mg kg-1) or NAC (2.5 mg kg-1) but not ENA (1 mg kg-1) was administered intraperitoneally (i.p.) 30 min before GTN. Furthermore, in control rats, CPT or NAC but not ENA given i.p. 30 min before GTN, potentiated its haemodynamic effects. These effects were blocked by methylene blue (10 mg kg-1). At the same doses, CPT or NAC did not affect the hypotensive effects of SIN-1. 3. The reduced ability of cultured tolerant smooth muscle cells (SMC, 24 x 103 cells) or endothelial cells(EC, 40 x 103 cells) to potentiate the anti-platelet effects of GTN (44 microM) was restored by CPT or NAC but not by ENA or glutathione (all at 0.5 mM). Potentiation of the anti platelet effects of tolerant SMC or EC by CPT or NAC was abolished by co incubation with oxyhaemoglobin (Oxy-Hb, 10 microM)indicative of nitric oxide (NO) formation.4. When GTN (150-2400 microM) was incubated with CPT, NAC or glutathione but not ENA (all at 0.1 mM) for 30 min in Krebs buffer at 37 degrees C a concentration-dependent increase in nitrite (NO2-)formation was observed. 5. The antiplatelet effects of GTN (5.5-352 microM) were potentiated by co incubation with CPT or NAC but not with ENA or glutathione (all at 0.5 mM). The concentration of GTN required to inhibit platelet aggregation by 50% (IC50) was 110 +/- 2 microM for GTN alone, 14 +/- 2 microM for GTN in the presence of NAC and 30 +/- 2 microM for GTN in the presence of CPT. The potentiation of the effects of GTN by CPT or NAC was inhibited by co-incubation with Oxy-Hb (10 microM). By themselves, CPT or NAC did not inhibit platelet aggregation.6. The ability of CPT to restore (a) the haemodynamic effects of GTN in tolerant rats and (b) the reduced capacity of tolerant SMC or EC to potentiate the anti platelet effects of GTN is not related to its ACE inhibitory activity.7. CPT also potentiated the hypotensive effects of GTN in non-tolerant rats, and in vitro CPT released NO from GTN in the absence of a GTN to NO converting cell, so that it is unlikely that reversal of tolerance by CPT is due to the replenishment of intracellular thiols. Rather it can be explained by the ability of CPT to release NO from GTN in the extracellular space. This extracellular formation of NO from GTN by CPT would then compensate for the impaired enzymic biotransformation of GTN to NO that develops during tolerance as was originally proposed for NAC. PMID- 8358545 TI - Effects of prolonged application of isoprenaline on intracellular free magnesium concentration in isolated heart of rat. AB - 1. The effect of prolonged application of isoprenaline on intracellular free-Mg2+ concentration ([Mg2+]i) was examined by use of 31P-nuclear magnetic resonance (31P-n.m.r.) in rat isolated hearts. Left ventricular pressure (LVP) was simultaneously measured. 2. [Mg2+]i was estimated from the separation of the alpha- and beta-ATP peaks, using the dissociation constant of MgATP 38 microM (established previously). In normal (phosphate-free, Krebs-Henseleit) solution, [Mg2+]i was approximately 0.4 mM. 3. When isoprenaline was applied for 100 min, a transient increase in [Mg2+]i was observed during the initial 25 min, whilst concentrations of ATP ([ATP]) and phosphocreatine ([PCr]) decreased and [Pi] correspondingly increased. During the subsequent 75 min of isoprenaline application, [Mg2+]i decreased below its resting levels. Washout of isoprenaline restored [Mg2+]i and [PCr], but [ATP] remained low. These changes elicited by isoprenaline were not observed in the presence of propranolol, a typical alpha adrenoceptor blocker. 4. Isoprenaline increased both LVP and heart rate. The increased LVP and heart rate slowly returned to lower values during prolonged application of isoprenaline, but remained higher than those before application. 5. The transient rise in [Mg2+]i elicited by isoprenaline could be attributed to the decrease in [ATP] resulting in a release of Mg2+. The subsequent decrease in [Mg2+]i during the prolonged applications suggests that beta-adrenoceptor stimulation itself facilitates Mg(2+)-extruding mechanism(s). PMID- 8358546 TI - Blockade by glibenclamide of the flow-evoked endothelial release of ATP that contributes to vasodilatation in the pulmonary vascular bed of the rat. AB - 1. The effect of step augmentation of flow rate on the level of adenosine -5' triphosphate (ATP) measured in the Krebs perfusate was investigated, and the effect of glibenclamide on the release of ATP was tested in the rat pulmonary vascular bed. 2. For flow rates between 10.38 +/- 1.18 and 28.88 +/- 2.08 ml min 1 (n = 8) 1 microM suramin, a P2-purinoceptor antagonist, significantly (P < 0.05) increased vascular resistance under conditions of step augmentation of flow rate. This suggests that endogenous ATP released during increases in flow rate dilates pulmonary vessels. 3. In response to a step augmentation in flow rate from 9.13 +/- 0.97 to 18.3 +/- 1.69 ml min-1 (n = 4) ATP levels were up to 23 fold higher (P < 0.05) for 15 s, and gradually dropped to a level of about half the initial rise. Once the ATP levels had stabilized, another step augmentation of flow rate to 27.00 +/- 3.49 ml min-1 was able to evoke a corresponding increase of ATP release. The ability of the vascular bed to respond with increased ATP release after the initial ATP responses had tapered, demonstrates that the drop in ATP levels after the initial rise is not due to depletion of ATP. Furthermore, the maximal ATP response directly precedes the vasodilatation observed following each jump in perfusion pressure produced with each step increase in flow rate. 4. In response to two 3 fold step augmentations of flow rate (8.41-27.29 ml min-1) spaced 30 min apart there were two increases in the level of ATP which were not significantly different from each other.However, perfusion with 1 microM glibenclamide between the first and the second step augmentation of flow rate (8.08-24.67 ml min-1) significantly (P<0.05; n = 6) blocked the increase in ATP release. This suggests that the release of intracellular ATP is mediated by glibenclamide-sensitive K+ channels.5. A concentration of 1 microM glibenclamide perfused for 30 min was without effect on vascular pressure at constant flow. However, under conditions where flow was augmented in a stepwise manner (between 11.50 and 36.45 ml min-1) perfusing with 1 microM glibenclamide increased vascular resistance (P <0.10).6. It is concluded that flow-induced ATP release is mediated by a glibenclamide-sensitive K+ channel,and that the release of ATP from endothelial cells probably functions to vasodilate the pulmonary vascular bed of the rat. PMID- 8358548 TI - Reciprocal interaction of 5-hydroxytryptamine and cholecystokinin in the control of feeding patterns in rats. AB - 1. The effect of the CCKA receptor antagonist, devazepide (100 mg kg-1) on meal parameters during the initial phase of the dark period was studied in free feeding rats by use of a procedure for continuously monitoring feeding patterns. 2. In a second experiment, the effect of devazepide on the reduction in meal parameters induced by the 5-hydroxytryptamine (5-HT) releaser and uptake inhibitor, (+)-fenfluramine (1.5 mg kg-1) in 4 h food-deprived rats was examined. 3. The hypophagic effect of an intraperitoneal injection of cholecystokinin (CCK 8, 4 micrograms kg-1) was studied in rats treated with the 5-HT receptor antagonist, metergoline (1 and 2 mg kg-1). 4. Devazepide increased the size of the first meal in free-feeding, but not in 4 h food-deprived rats and partially antagonized the effect of (+)-fenfluramine on the size and duration of the first meal. The reduction in eating rate induced by (+)-fenfluramine was not modified by devazepide. No changes in (+)-fenfluramine or (+)-norfenfluramine levels were found in the brain of rats treated with devazepide. 5. The effect of CCK-8 on meal size was completely antagonized by 2 mg kg-1 metergoline. A significant interaction was also found between 2 mg kg-1 metergoline and CCK-8 as regards their effect on the inter-meal interval. 6. The results suggest a reciprocal interaction between 5-HT and CCK-8 in enhancing the satiating effect of food in rats. PMID- 8358547 TI - Induction of endothelium-dependent relaxation in the rat aorta by IRL 1620, a novel and selective agonist at the endothelin ETB receptor. AB - 1. The effects of a novel and selective agonist at the endothelin ETB receptor, IRL 1620 (Suc-[Glu9, Ala11,15] endothelin-1 (8-21)), were examined in the isolated aorta of the rat. 2. IRL 1620 (1-300 nM) changed neither the resting tone nor the cytosolic Ca2+ level ([Ca2+]i) of the aorta without endothelium. In the presence of endothelium, however, IRL 1620 increased endothelial [Ca2+]i with little effect on the muscle tone. In the absence of external Ca2+, IRL 1620 still induced a transient increase in endothelial [Ca2+]i. 3. Noradrenaline (100 nM) increased both muscle [Ca2+]i and tension. IRL 1620 (1-300 nM) relaxed the muscle with an increase in endothelial [Ca2+]i only in the presence of endothelium. An inhibitor of nitric oxide synthase, 100 microM NG-monomethyl-L-arginine, inhibited the relaxant effect of IRL 1620 but not the increase in endothelial [Ca2+]i. 4. In resting and noradrenaline-stimulated aorta, the effects of IRL 1620 were inhibited by a selective antagonist of the ETB receptor, IRL 1038 (0.3 3 microM), although a selective antagonist of the ETA receptor, BQ-123 (3 microM), was ineffective. Verapamil (10 microM) did not alter the effects of IRL 1620. 5. A muscarinic receptor agonist, carbachol (1 microM), also induced endothelium-dependent relaxation with an increase in endothelial [Ca2+]i. However, the effects of carbachol were not inhibited by the ETB antagonist, IRL 1038 (3 microM). 6. These results suggest that IRL 1620 is a selective agonist at the ETB receptor which increases endothelial [Ca2+]i by releasing Ca2+ from storage sites and by opening non-L type Ca2+ channels,activates nitric oxide synthase, releases nitric oxide, and relaxes vascular smooth muscle. PMID- 8358549 TI - Investigations of the dual contractile/relaxant properties showed by antioquine in rat aorta. AB - 1. In the present study we assessed the activity of antioquine, a bisbenzyltetrahydroisoquinoline alkaloid isolated from Pseudoxandra sclerocarpa, by examining its effects on the contractile activity of rat isolated aorta, specific binding of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin to cerebral cortical membranes and the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta. 2. Contractions in rat aorta induced by high concentrations of KCl (80 mM) and noradrenaline (1 microM) were inhibited by antioquine in a concentration-dependent manner (0.1 microM- 300 microM). The alkaloid appeared more potent against KCl-induced contractions. This inhibitory effect was observed at both 37 degrees C and 25 degrees C. 3. Paradoxically, at the highest concentration tested (300 microM) antioquine induced a contractile response of similar magnitude in the presence and absence of extracellular calcium, at 37 degrees C. This activity was greatly attenuated at 25 degrees C. Antioquine-induced contractions were not inhibited by prazosin (0.1 microM), nifedipine (1 microM) or diltiazem (100 microM). On the contrary, prazosin and nifedipine slightly increased the contractions in the presence of extracellular calcium. Papaverine (100 microM) partially inhibited the contractile response to antioquine both in the presence and absence of extracellular calcium. 4. At 25 degrees C, in Ca(2+)-free solution, antioquine (300 microM) did not modify the contractile response (phasic and tonic) evoked by noradrenaline, but increased the phasic contraction induced by caffeine. At 37 degrees C, the contraction elicited by antioquine made it impossible to observe the noradrenaline-induced one. 5. Antioquine showed affinity for the [3H] prazosin binding site and for the [3H]-(+)-cis-diltiazembinding site of the Ca2+ channel receptor complex, but had no effect at the dihydropyridine binding site in rat cerebral cortex.6. Antioquine weakly inhibited some PDE forms isolated from bovine aorta: a CaM-PDE (PDE I)which preferentially hydrolyzes cyclic GMP and is activated by calmodulin, and a rolipram-sensitive cyclic AMP-PDE (PDE IV) which hydrolyzed cyclic AMP. Antioquine did not exert any inhibitory effect on the other forms of PDE, a cyclic GMP selective form (PDE V) and a low Km cyclic AMP-PDEthat is inhibited by cyclic GMP (CGI-PDE, PDE III).7. The present work provides evidence that antioquine has properties both as a calcium entry blocker(possibly through the benzothiazepine recognition site in the calcium channel) and as a contractile agent.Its mechanism of action as a contractile agent is not related to Ca2+-entry and is hypothetically similar to that of calyculin-A or okadaic acid. The possible involvement of a-adrenoceptors in this paradoxical effect cannot be excluded. The rigidity of the molecule provides an interesting model for analyzing this contractile mechanism and the intracellular processes involved. PMID- 8358550 TI - Activation by calcium alone of chloride secretion in T84 epithelial cells. AB - 1. The goal of this study was to determine if an increase in cytoplasmic calcium concentration ([Ca2+]i), in the absence of additional second messengers derived from membrane phospholipid turnover, is a sufficient signal to induce chloride secretion across monolayers of the human colonic epithelial line, T84. 2. Thapsigargin was used to increase [Ca2+]i by inhibiting the endomembrane Ca(2+) ATPase. [Ca2+]i was monitored in monolayers by fura-2 fluorescence spectroscopy, chloride secretion by measuring changes in short circuit current (Isc) in modified Ussing chambers, and inositol phosphates were measured by radio-h.p.l.c. of extracts of cells prelabelled with [3H]-inositol. 3. Thapsigargin increased [Ca2+]i and Isc in parallel, without increasing any inositol phosphates. The effect of thapsigargin on Isc was abolished by the intracellular calcium chelator, bis-(o-aminophenoxy)-ethane-N,N,N',N"-tetraacetic acid (BAPTA). 4. Increasing [Ca2+]i with thapsigargin did not prevent a subsequent calcium response to carbachol or histamine if extracellular calcium was available. In the absence of extracellular calcium, only one such release of calcium to hormonal stimulation occurred when cells were pretreated with thapsigargin, and a second response to either carbachol histamine was essentially abolished. 5. Addition of carbachol or histamine to thapsigargin-treated cells mounted in Ussing chambers caused a transient further increase in Isc followed by termination of the response, even though [Ca2+]i continued to rise. 6. We conclude that an elevation in [Ca2+]i is a sufficient signal to induce chloride secretion in T84 cells. Rather than being required to stimulate secretory responses, additional second messengers induced by hormonal secretagogues (such as inositol phosphates) may in fact serve to limit the secretory response. PMID- 8358551 TI - On the high affinity binding site for [3H]-1,3-dipropyl-8-cyclopentylxanthine in frog brain membranes. AB - 1. Radioligand binding properties of the adenosine receptor ligands, [3H]-1,3 dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), and [3H]-R-phenylisopropyladenosine ([3H]-R-PIA) were investigated in frog brain membranes. 2. The specific binding of the adenosine antagonist, [3H]-DPCPX to frog brain membranes showed one binding site with Kd and Bmax values of 43.8 nM and 0.238 +/- 0.016 pmol mg-1 protein, respectively. Guanosine 5'-triphosphate (GTP, 100 microM) decreased to 72 +/- 7% and Mg2+ (8 mM) increased to 121 +/- 3% [3H]-DPCPX (40 nM) binding to frog brain membranes. 3. [3H]-DPCPX saturation binding experiments performed in the presence of Mg2+ (8 mM), or in the presence of GTP showed that Mg2+ ions decreased the Kd value of [3H]-DPCPX to 14 nM, and GTP increased this value to 65.6 nM. Bmax values were not significantly (P > 0.05) modified (0.261 +/- 0.018 pmol mg-1 protein, with Mg2+, and 0.266 +/- 0.026 pmol mg-1 protein, in presence of GTP) by the presence of Mg2+ or GTP. 4. The specific binding of [3H]-R-PIA (15 nM) was decreased to 37 +/- 6% by GTP (100 microM) and increased to 123 +/- 4% by Mg2+ (8 mM). [3H]-R-PIA saturation binding experiments performed in the presence of Mg2+ (8 mM) showed one binding site with Kd and Bmax values of 0.9 nM and 0.229 +/- 0.008 pmol mg-1 of protein, respectively. 5. The concentration inhibition curves of adenosine agonists and antagonists versus [3H]-DPCPX binding showed the following order of potencies: CPA> R-PIA~ NECA> S-PIA> > CGS 21680, for the agonists, and XAC ~-DPCPX> > XCC> PACPX, for the antagonists.6. The present results suggest that the adenosine binding site in the frog brain membranes is G-protein coupled, but that the antagonist affinities and the pharmacological profile is different from the Al or A2 adenosine receptors. PMID- 8358552 TI - Roles of prostacyclin, EDRF and active oxygens in leukocyte-dependent platelet adhesion to endothelial cells induced by platelet-activating factor in vitro. AB - 1. The mechanism of polymorphonuclear leukocyte (PMN)-dependent platelet adhesion to cultured endothelial cells induced by platelet-activating factor (PAF) was investigated to determine whether PMNs release or generate any factor(s) capable of inducing platelet adhesion, and the roles of prostacyclin and endothelium derived relaxing factor (EDRF). 2. Cell-free supernatants, sonicates or rapid filtrates of PAF-stimulated PMN suspensions did not induce platelet adhesion to endothelial cells, but the PMN sonicates induced platelet adhesion when endothelial cells were pretreated with both aspirin and NG-nitro-L-arginine (L NOARG). Its microphotograph showed that mainly platelet aggregates adhered to the endothelial cell surface. 3. Platelet adhesion induced by the PMN sonicates to aspirin- and L-NOARG-pretreated endothelial cells was dose-dependently prevented by OP-41483 (1-100 nM), and slightly by L-arginine (1 mM). The inhibition of platelet adhesion by OP-41483 and L-arginine was potentiated by their combination. 4. WEB 2170 (3 microM), a PAF antagonist, inhibited platelet adhesion induced by the PMN sonicates. However, PAF alone did not induce significant platelet adhesion to aspirin- and L-NOARG-treated endothelial cells. 5. Platelet adhesion induced by the PMN sonicates was not suppressed by AA-861 and indomethacin. However, both superoxide dismutase and catalase significantly inhibited platelet adhesion, and, in combination, their inhibitory effect was synergistically potentiated. Mannitol had no effect. It was also significantly inhibited by alpha 1-antitrypsin, whereas chymostatin and elastatinal had no effect. 6. PAF-induced platelet adhesion to endothelial cells in the presence of intact PMNs was not suppressed by indomethacin and AA-861, or by protease inhibitors. SOD alone, and in combination with catalase, caused a slight but significant inhibition, while catalase and mannitol by themselves had no effect.7. PMN-induced platelet adhesion was slightly inhibited by OP-41483 (100 nM). L-Arginine (1 mM)alone had no effect, but slightly potentiated the effect of OP-41483. This platelet adhesion was not accompanied by suppression of prostacyclin synthesis.8. The results with the PMN sonicates show that prostacyclin, EDRF and active oxygens are important modulators of intercellular interactions between platelets and endothelial cells. These results further suggest that the mechanism of intact PMN-dependent platelet adhesion is primarily through platelet endothelial cell interactions in which leukocyte-derived active oxygens play a role, but does not involve platelet-platelet interactions inhibitable by prostacyclin. PMID- 8358553 TI - Mediation of endothelin-1-induced inhibition of platelet aggregation via the ETB receptor. AB - 1. The effects of FR139317 (ETA antagonist) or PD145065 (non-selective ETA/ETB antagonist) on endothelin-1 (ET-1)-induced changes in blood pressure and inhibition of ex vivo platelet aggregation were investigated in the anaesthetized rabbit. 2. ET-1 (1 nmol kg-1, i.a. bolus) caused a sustained increase in mean arterial pressure (MAP) (peak increase 47 +/- 5 mmHg, n = 8). Intravenous infusion of FR139317 at 0.2 (n = 4) or 0.6 mg kg-1 min-1 (n = 4) inhibited the ET 1 pressor response by 83 or 89%, respectively. Infusion of PD145065 at 0.2 (n = 4) or 0.6 mg kg-1 min-1 (n = 4) inhibited the ET-1-induced increase in MAP by 79 or 75%, respectively. 3. The transient depressor response (-16 +/- 3 mmHg) which preceded the rise in blood pressure induced by ET-1 (1 nmol kg-1, i.a., n = 8) was enhanced by an intravenous infusion of FR139317 (0.6 mg kg-1 min-1) to -35 +/ 5 mmHg (P < 0.05, n = 4). This enhancement was abolished by indomethacin (5 mg kg-1, i.v.) pretreatment (-17 +/- 1 mmHg, n = 4). PD145065 (0.2 mg kg-1 min-1, i.v.) attenuated the ET-1-induced fall in blood pressure to -9 +/- 1 mmHg (n = 4), while a higher dose of this antagonist (0.6 mg kg-1 min-1, i.v.) completely abolished the ET-1-mediated depressor response. 4. ET-1 (1 nmol kg-1, n = 8) inhibited ex vivo platelet aggregation by 96% at 5 min after injection of the peptide. FR139317 (0.2 or 0.6 mg kg-1 min-1, i.v.) or PD145065 (0.2mg kg-1 min-1, i.v.) did not affect the inhibition of ex vivo platelet aggregation in response to ET-1. In contrast, intravenous infusion of PD145065 (0.6 mg kg-1 min-1) abolished the anti-aggregatory effects of ET-1.5. Thus, FR139317 inhibits the pressor, but not the depressor actions of ET-1 and has no effect on the ET-l induced inhibition of ex vivo platelet aggregation. In contrast, PD145065 antagonizes the pressor and depressor responses to ET-1 and abolishes the anti aggregatory effects of the peptide.6. These results strongly suggest that ET-1 induced vasoconstriction in the anaesthetized rabbit is primarily mediated via the ETA receptor while the depressor and antiaggregatory actions of ET-1 are due to activation of the ETB receptor. PMID- 8358554 TI - Action of alpha-dendrotoxin on K+ currents in nerve terminal regions of axons in rat olfactory cortex. AB - 1. In the rat olfactory cortex, unmyelinated axons give rise to synapses en passant. This tissue was used to study the pharmacology of axonal K(+)-currents. Responses were measured from a group of these axons as unclamped field currents, with a polarizable suction electrode. 2. A single stimulus to the axons elicited a tetrodotoxin-sensitive Na(+)-dependent transient K(+)-currents were revealed by positive polarization of the suction electrode and were manifest as a negative current following the Na(+)-component. 3. In the presence of tetraethylammonium (TEA, 5 mM) and Cd2+ (100 microM), the K(+)-component was depressed by 3,4 diaminopyridine (3,4-DAP; 1 to 20 microM; IC50 2.0 +/- 0.4 microM). alpha Dendrotoxin (DTX; 15-1500 nM) also attenuated the aminopyridine-sensitive component (IC50 93 +/- 4 nM). At the highest DTX concentration, depression of the K(+)-current was incomplete, the residual K+ current being reduced by 3,4-DAP (0.1 to 5 microM). 4. These results indicate the presence of two aminopyridine sensitive K+ currents in this preparation distinguished by their susceptibility to DTX. PMID- 8358555 TI - Differential localization of endothelin ETA and ETB binding sites in human placenta. AB - 1. The localization and differential distribution of endothelin (ET) receptor subtypes (ETA and ETB) was investigated in sections of human placenta by use of quantitative in vitro autoradiography and receptor selective ligands. 2. Specific, high density [125I]-ET-1 binding sites were localized to the decidua and foetal membranes as well as to arteries and veins in the chorionic plate and throughout the villous tree. Moderate to low density binding was found in the extravillous and villous trophoblast respectively. 3. [125I]-ET-1 binding sites exhibited a rank order of inhibition by unlabelled peptide sequences (ET-1 > ET-3 > [Ala3,11,18Nle7]-ET-1 > BQ123 > or = sarafotoxin 6c). However, in contrast to the monophasic inhibition curve of ET-1, the other sequences produced a significantly better fit to a two component inhibition curve suggesting the presence of a heterogeneous population of ET binding sites. 4. ETA and ETB receptors were distinguished by competitive inhibition of [125]-ET-1 binding with increasing concentrations of unlabelled ET-3, [Ala3,11,18Nle7]-ET-1, sarafotoxin 6c and BQ123 and by incubating sections with the ETB agonist, [125I]-BQ3020. ET receptor subtypes exhibited a differential distribution in the placenta. ETA type binding sites predominated (approximately 80% of the total) on veins and arteries in the chorionic plate. Veins in stem villi, blood vessels in distal regions of the villous tree and decidual cells displayed a high density (approximately 60 70% of the total) of the ETB receptor subtype. 5. No difference was detected in either the relative density of [125I]-ET-1 binding sites or the proportion of ETA to ETB sites in placentae from pregnancies complicated by pre-eclampsia compared with normal term controls.6. ET may have a local autocrine or paracrine role in the placenta, acting via specific receptors to influence foetoplacental blood flow and other aspects of placental function. PMID- 8358556 TI - A comparison of the effects of polyarginine and stimulated eosinophils on the responsiveness of the bovine isovolumic bronchial segment preparation. AB - 1. The bovine isovolumic bronchial segment preparation has been used to study the sensitivity and responsiveness of bronchial smooth muscle after various manipulations. 2. Addition of acetylcholine (ACh) to the lumen of the segments elicited an increase in intraluminal pressure as a result of contraction of the airway smooth muscle. However, the increases in intraluminal pressure were greater when the ACh was added to the adventitial surface of the preparation. 3. Addition of polyarginine to the bronchial lumen for 60-120 min resulted in an increased magnitude of response and greater than 100 fold increase in sensitivity to ACh administered into the lumen. Depolarizations induced by KCl were similarly enhanced when the solution was added into the lumen. In contrast, the sensitivity and responsiveness to ACh or K(+)-induced depolarization administered adventitially was unchanged. 4. The mechanical disruption of the epithelium produced a 32 fold increase in sensitivity to ACh introduced via the lumen, whereas the sensitivity to ACh added adventitially remained unaltered. 5. Addition of polyarginine to the adventitial bathing medium resulted in no change in the responsiveness or sensitivity to ACh, irrespective of whether the ACh was given intraluminally or adventitially. 6. Histological examination revealed that polyarginine caused extensive disordering of the normal architecture of the bronchial epithelium. Taken together with the unaltered responsiveness to adventitial ACh (i.e. lack of change in intrinsic muscle sensitivity) these observations suggest that the effect of polyarginine was most likely due to disruption of a diffusion barrier. 7. In contrast to the effects of polyarginine, the only effect of stimulated eosinophils was to produce a small diminution in the responsiveness to ACh that had been added adventitially. PMID- 8358557 TI - Hoe 694, a new Na+/H+ exchange inhibitor and its effects in cardiac ischaemia. AB - 1. The benzoylguanidine derivative Hoe 694 ((3-methylsulphonyl-4- piperidino benzoyl) guanidine methanesulphonate) was characterized as an inhibitor of Na+/H+ exchange in rabbit erythrocytes, rat platelets and bovine endothelial cells. The potency of the compound was slightly lower or comparable to ethylisopropyl amiloride (EIPA). 2. To investigate a possible cardioprotective role of the Na+/H+ exchange inhibitor Hoe 694, rat isolated working hearts were subjected to ischaemia and reperfusion. In these experiments all untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 10(-7) M Hoe 694 to the perfusate almost abolished reperfusion arrhythmias in the rat isolated working hearts. 3. Hoe 694 reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), which are indicators of cellular damage during ischaemia, into the venous effluent of the hearts by 60% and 54%, respectively. 4. The tissue content of glycogen at the end of the experiments was increased by 60% and the high energy phosphates ATP and creatine phosphate were increased by 240% and 270% respectively in the treated hearts as compared to control hearts. 5. Antiischaemic effects of the Na+/H+ exchange inhibitor, Hoe 694, were investigated in a second experiment in anaesthetized rats undergoing coronary artery ligation. In these animals, pretreatment with Hoe 694 caused a dose dependent reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation down to doses of 0.1 mg kg-1, i.v. Blood pressure and heart rate remained unchanged. 6. We conclude that the new Na+/H+ exchange inhibitor, Hoe 694, shows cardioprotective and antiarrhythmic effects in ischaemia and reperfusion in rat isolated hearts and in anaesthetized rats. In view of the role which Na+/H+ exchange seems to play in the pathophysiology of cardiac ischaemia these effects could probably be attributed to Na+/H+ exchange inhibition. PMID- 8358558 TI - Kinetic study of the tubular dopamine outward transporter in the rat and dog kidney. AB - 1. The present study has determined the kinetic characteristics of the outflow of dopamine of renal origin in slices of rat and dog renal cortex loaded with exogenous L-dihydroxyphenylalanine (L-DOPA 5 to 5000 microM). 2. In both dog and rat renal tissues the production of dopamine was found to be dependent on the concentration of L-DOPA used and reached its maximum at 2500 microM L-DOPA. The decarboxylation of L-DOPA in rat cortical slices (16.4 +/- 2.6 to 1479.2 +/- 85.2 nmol g-1) was 6 fold that in the dog (2.2 +/- 0.4 to 252.1 +/- 21.2 nmol g-1). In the rat kidney a large amount (approximately 50%) of the dopamine (5.2 +/- 0.6 to 743.4 +/- 58.3 nmol g-1) was found to escape into the incubation medium, whereas in dog renal slices the amount of newly-formed dopamine escaping into the incubation medium (0.7 +/- 0.2 to 46.5 +/- 9.3 nmol g-1) was less than 25% of the total amount of the amine formed. 3. The application of the Michaelis-Menten equation to the net transport of newly-formed dopamine has allowed the identification of a saturable (carrier-mediated transfer) and a non-saturable component (diffusion). The Vmax (nmol g-1 15 min-1) and Km (nM) values for the saturable component were, respectively, 340 +/- 41 and 396 +/- 45 in the rat kidney and 112 +/- 16 and 319 +/- 35 in the dog kidney. In both rat and dog renal tissues, the magnitude of the non-saturable component was found to be of minor importance up to a concentration of 250 nmol g-1 of dopamine to be transported. At high concentrations of the amine (greater then 250 nmol g-1), only attainable in rat kidney slices, most of the dopamine was found to leave the compartment where the synthesis did occur through a non-saturable transport system.4. In conclusion, the results presented here show that the outflow of newly-formed dopamine in both dog and rat kidney slices loaded with exogenous L-DOPA follows Michaelis-Menten kinetics with a saturable component and a non-saturable one, the latter assuming particular importance only at higher concentrations of the amine. PMID- 8358559 TI - The antiarrhythmic effects of the nucleoside transporter inhibitor, R75231, in anaesthetized pigs. AB - 1. The effect of R75231, an inhibitor of purine nucleoside transport, were examined on ischaemic arrhythmias in anaesthetized pigs. 2. In closed chest pigs (n = 4), R75231 exerted a moderate dose-dependent decrease in mean arterial blood pressure (from 97 +/- 4 mmHg to 95 +/- 4, 90 +/- 1 and 83 +/- 2 mmHg at 25, 50 and 100 micrograms kg-1 respectively) and produced a dose-related shift to the left of the blood pressure dose-response curve to intravenous bolus doses of adenosine. The degree of inhibition of adenosine uptake by R75231, assessed ex vivo in erythrocyte suspensions, was 43 +/- 5%, 64 +/- 13 and 114 +/- 15% at doses of 25, 50 and 100 micrograms kg-1 respectively. 3. In open chest pigs, intravenous injection of R75231 (50 micrograms kg-1; n = 6 and 100 micrograms kg 1; n = 10) induced a dose-related decrease in both systolic and diastolic arterial blood pressure which was more marked than in closed-chest pigs (mean pressure 86 +/- 4 to 70 +/- 2 mmHg and 88 +/- 6 to 60 +/- 6 mmHg with 50 and 100 micrograms kg-1 respectively), without affecting heart rate or myocardial contractility. Coronary artery occlusion in these pigs caused a secondary decrease in blood pressure. This was not observed in controls (n = 10). The lower dose of R75231 did not exert any antifibrillatory effects, whereas the higher dose significantly reduced the incidence of ventricular fibrillation, from 80% in control pigs to 30%. Neither dose modified the incidence of ventricular tachycardia (33% and 40% with 50 and 100 microg kg-1 respectively, compared to 30% in controls) or had any effect on the total number of ventricular ectopic beats (85 +/- 47 and 130 +/- 31 vs 110 +/- 19 in controls). R75231, at a dose of 100 microg kg-1, also attenuated the ischaemia-induced shortening of QRS interval, but neither dose modified the ST-segment depression seen following occlusion.4. These results show that the nucleoside transport inhibitor, R75231, exerts an antifibrillatory effect ina model of severe myocardial ischaemia in a dose which completely inhibits adenosine uptake ex vivo.However, while this agent has minimal haemodynamic effects in closed chest animals, the reduction in blood pressure induced by R75231 in open-chest pigs cannot be excluded as a possible contributory mechanism of the antiarrhythmic effects of this drug. PMID- 8358560 TI - 5-HT1B receptors mediate potent contractile responses to 5-HT in rat caudal artery. AB - 5-Hydroxytryptamine (5-HT) evoked potent contractile responses in phenoxybenzamine-treated ring segments of rat caudal artery, partially contracted with U46619. Responses were mimicked by 5-HT1-selective agonists with the potency order: RU24969 > 5-carboxamidotryptamine > 5-HT = CP-93,129 >> sumatriptan. 8 Hydroxy-N,N-dipropylaminotetralin was virtually inactive. Responses were unaffected by spiperone (0.1 microM) and mesulergine (1.0 microM), but were antagonized competitively by (+/-)-cyanopindolol affording agonist-independent pKB estimates of 8.4 to 8.9. The pharmacological profile of this receptor is consistent with that of the 5-HT1B subtype. Since the 5-HT1B receptor is the rodent homologue of the 5-HT1D beta subtype, it might be anticipated that 5-HT1D beta receptors will be found to mediate vasoconstrictor responses in non-rodent species. PMID- 8358561 TI - Oestradiol inhibits smooth muscle cell proliferation of pig coronary artery. AB - 1. The effect of oestradiol 17 beta on vascular smooth muscle proliferation was examined in segments of the pig left anterior descending coronary artery (LAD). It was established by cytochemical techniques that out-growth from the segments was composed of vascular smooth muscle cells. 2. [3H]-thymidine uptake by pig LAD segments was used as an index of vascular smooth muscle cell proliferation. Nitroprusside and forskolin significantly inhibited [3H]-thymidine uptake and were used as positive controls. 3. Oestradiol 17 beta (180-360 nM) inhibited thymidine uptake by pig LAD segments (P < 0.05). The inhibition was observed only in the absence of phenol red, which is a weak oestrogen receptor agonist. The anti-oestrogens tamoxifen and its more potent metabolite 4-hydroxytamoxifen, both of which are partial oestrogen receptor agonists, also significantly inhibited thymidine uptake. However, pretreatment with either tamoxifen or 4 hydroxytamoxifen did not significantly block oestradiol 17 beta-induced inhibition of thymidine uptake. 4. The LAD segments bound [3H]-oestradiol 17 beta in a time-dependent manner and about 20 to 30% was displaced by an excess of unlabelled oestradiol 17 beta. Autoradiography showed [3H]-oestradiol 17 beta was evenly distributed in the cytosol and nuclei of cells in the three layers of the vessel wall. 5. The data suggest that oestradiol 17 beta inhibits smooth muscle cell proliferation in porcine LAD segments, possibly through an oestrogen receptor mechanism. This in vitro effect suggests an in vivo role for oestradiol 17 beta in directly protecting coronary arteries against myointimal proliferation in premenopausal women. PMID- 8358562 TI - Development of a radioligand binding assay for 5-HT4 receptors in guinea-pig and rat brain. AB - 1. The 5-HT4 receptor antagonist, GR113808, has been radiolabelled to a high specific activity with tritium. 2. Characterization of specific [3H]-GR113808 binding in homogenates of guinea-pig striatum and hippocampus revealed a single site of high affinity (Kd values 0.20 and 0.13 nM respectively). 3. [3H]-GR113808 binding was reversible and displayed rapid kinetics such that association and dissociation were complete within 3 min. 4. Specific [3H]-GR113808 binding was potently and stereoselectively inhibited by agonists and antagonists acting at the 5-HT4 receptor but not by compounds selective for other 5-HT receptors or other neurotransmitter receptors. 5. Autoradiographic analysis revealed a discrete localization in both guinea-pig and rat brain with high concentrations of binding in brain areas such as the striatum, substantia nigra and olfactory tubercle. 6. [3H]-GR113808 binding to homogenates of guinea-pig striatum meets the criteria for labelling of the 5-HT4 receptor and, as such, represents the first characterization of this receptor in a radioligand binding assay. PMID- 8358563 TI - Vasorelaxant mechanism of KRN2391 and nicorandil in porcine coronary arteries of different sizes. AB - 1. The relaxant mechanisms of action of KRN2391, a novel vasodilator, and nicorandil on epimyocardial coronary artery (2.5- 3.0 mm outer diameter) and mid myocardial coronary artery (0.8-1.0 mm outer diameter) were investigated in porcine isolated coronary arteries. In addition, the vasorelaxant responses of KRN2391 and nicorandil were compared with those of nitroglycerin and cromakalim, a K+ channel opener, in epi- and mid-myocardial coronary arteries. 2. Nitroglycerin showed a more potent relaxant effect on epi-myocardial coronary arteries than on mid-myocardial coronary arteries, whereas cromakalim produced greater relaxation responses in mid-myocardial coronary arteries. There was no difference between epi- and mid-myocardial coronary arteries in terms of the relaxant effect of KRN2391 and nicorandil. 3. Relaxation induced by KRN2391 in epi- and mid-myocardial coronary arteries was inhibited by oxyhaemoglobin, a pharmacological antagonist of nitrovasodilators, and glibenclamide, a pharmacological antagonist of K+ channel opening drugs. However, the inhibitory effect of glibenclamide on KRN2391-induced relaxation was greater in mid myocardial coronary artery than in epi-myocardial coronary artery. 4. Relaxation induced by nicorandil was inhibited by oxyhaemoglobin alone in epi-myocardial coronary arteries and by both oxyhaemoglobin and glibenclamide in mid-myocardial coronary arteries. 5. In epi- and mid-myocardial coronary arteries, relaxation induced by cromakalim was inhibited by glibenclamide but not by oxyhaemoglobin, whereas relaxation induced by nitroglycerin was inhibited by oxyhaemoglobin but not by glibenclamide. 6. These results suggest that KRN2391 and nicorandil exhibit a dual mechanism of action acting partly as a nitrate and partly as a K+ channel opener. The mechanism of action of these drugs depend on the segment of coronary artery studied. Furthermore, the dual mechanism of action of KRN2391 and nicorandil seems to contribute to the equipotent relaxant effect between epi- and mid-myocardial coronary arteries. PMID- 8358564 TI - Cellular mechanism of the positive inotropic effect of hydralazine in mammalian myocardium. AB - 1. The purpose of this study was to elucidate the cellular mechanism of the positive inotropic effect of hydralazine, a vasodilator widely used for afterload reduction in patients with heart failure that has also been reported to have positive inotropic effects on the heart. After isolation, right ventricular papillary muscles from the ferret were maintained in bicarbonate-buffered salt solution (30 degrees C). A concentration-response relationship was obtained for hydralazine (10(-6) to 10(-3) M). In order to mimic different levels of catecholamine release found in heart failure, we utilized two methods of stimulation: (a) threshold punctate pulses and (b) suprathreshold punctate stimulation with voltage approximately 10% above threshold. 2. In a first group of muscles (n = 16), a maximally effective concentration of hydralazine (10(-3) M) increased peak isometric tension by 39 +/- 9% (P < 0.05). Doses lower than 10( 5) M had no significant effect. The bioluminescent Ca2+ indicator, aequorin, was loaded into a subset of these muscles (n = 7). A significant increase in peak light (i.e., intracellular Ca2+) developed, concurrently with an increase in peak tension (38 +/- 5% to 66 +/- 8%). This inotropic response was associated with a decrease in time to peak tension (ms), 221 +/- 7 to 186 +/- 5 (P < 0.05), and time to peak light, 65 +/- 4 to 52 +/- 2 (P < 0.05). These effects were markedly attenuated by pretreatment with autonomic blocking agents. 3. In a second group of muscles (n = 12), histamine was used to stimulate cyclic AMP production in the presence of propranolol. Hydralazine (3 x 10-4 M) led to a shift in the pD2 (i.e. the negative log of the concentration of histamine producing 50% of the maximal response) from 6.1 +/- 0.1 to 5.9 +/- 0.1(P <0.05), thus increasing the sensitivity of the muscles to histamine. Hydralazine also increased maximum tension from 160 +/- 77% to 195 +/- 57% (P <0.05) above baseline. Thus, hydralazine altered the potency and efficacy of histamine despite the presence of beta-adrenoceptor blockade.4. A third group of muscles were chemically skinned to examine the effects of hydralazine on myofilament Ca2+ responsiveness. Pretreatment of ferret papillary muscles with hydralazine (10-3 M)before skinning did not shift the force-pCa curve after skinning (n = 16). However, hydralazine added to previously skinned fibres desensitized the myofilaments, as indicated by a rightward shift of the force-pCa curve (n = 12). Maximum tension development was not changed.5. The pharmacological effects of hydralazine are characteristic of inotropic drugs that act mainly via cyclic AMP; however, the increase in peak tension demonstrated with histamine in the presence of hydralazine also suggests an effect on cyclic AMP-independent second messenger pathways. These data are consistent with reports that large doses of hydralazine may increase cellular levels of cyclic AMP, as well as other second messengers, by direct cardiac and indirect neuronal mechanisms. PMID- 8358565 TI - Effect of nafamostat mesilate on Na+ and K+ transport properties in the rabbit cortical collecting duct. AB - 1. To determine the mechanism(s) of hyperkalemia caused by nafamostat mesilate (NM), a serine-protease inhibitor, we investigated the effects of the drug on Na+ and K+ transport properties of the collecting duct (CD) cell in the isolated and perfused cortical collecting duct from rabbit kidneys. 2. NM at 10(-4) M in the lumen, hyperpolarized the apical membrane in parallel with increases in transepithelial resistance (RT) and fractional apical membrane resistance (fRA). 3. These effects were completely inhibited by pretreatment with 50 microM luminal amiloride, whereas they were not affected by luminal addition of 2 mM Ba2+. 4. NM at 10(-4) M in the bath slightly but significantly depolarized the basolateral membrane without any changes in RT or fRA, although NM at 10(-5) M in the bath had no effect on the electrical parameters. 5. It is concluded that NM mainly acts on the apical membrane of the CD cell and inhibits the amiloride-sensitive Na+ conductance in the apical membrane. PMID- 8358566 TI - Functional characterization of three adenosine receptor types. AB - 1. The purpose of the present study was to classify adenosine receptors into A1 and A2 subtypes in a wide range of isolated tissues and cell types (rat adipocytes and atria, guinea-pig ileum and atria (A1); guinea-pig aorta, dog coronary artery and human platelets and neutrophils (A2)) using the R- and S diastereoisomers of N-phenylisopropyladenosine (PIA), N-cyclopentyladenosine (CPA), the novel compound, N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR79236), N-[(2-methylphenyl)methyl]adenosine (metrifudil), 2 (phenylamino)adenosine (CV1808), and 2[[2-[4-(2-carboxyethyl)phenyl]ethyl]amino] N- ethylcarboxamidoadenosine (CGS21680); N-ethylcarboxamidoadenosine (NECA) was used as a standard. 2. Results obtained in all tissue preparations previously reported to contain A1-receptors could be described by a single rank order of agonist potency: CPA > or = GR79236, R-PIA > or = NECA >> S-PAI > or = metrifudil > or = CV1808, CGS21680. 3. In contrast, two distinct rank orders of agonist potency were observed in preparations previously reported to contain A2 receptors. In dog coronary artery, human neutrophils and platelets the rank order of potency was: CV1808, CGS21680 > or = NECA > R-PIA > or = metrifudil > or = CPA > GR79236 S-PIA. However, in guinea-pig aorta the rank order was: NECA > metrifudil > R-PIA, CPA > CV1808, GR79236 > or = S-PIA, CGS21680. 4. The results of this study are consistent with the existence of three types of adenosine receptor: A1-and two subtypes of A2-receptor. The receptor present in dog coronary artery, human platelets and neutrophils, probably corresponds to the A2a subtype, whilst that present in the guinea-pig aorta may be of the A2b subtype. PMID- 8358567 TI - Intracellular cross-talk between receptors coupled to phospholipase C via pertussis toxin-sensitive and insensitive G-proteins in DDT1MF-2 cells. AB - 1. The effect on intracellular free calcium concentration ([Ca2+]i) of simultaneous activation of receptors coupled to phospholipase C via pertussis toxin (PTX)-sensitive and -insensitive G-proteins has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF-2. 2. In fura-2-loaded DDT1MF-2 cells, activation of adenosine A1-receptors (which are linked to PTX sensitive G-proteins) with a maximal concentration of N6-cyclopentyladenosine (CPA; 300 nM) increased [Ca2+]i from 121 +/- 5 nM to 254 +/- 20 nM (n = 8). These experiments were performed in the presence of extracellular Ca2+. Stimulation of histamine H1-receptors (which are linked to PTX-insensitive G-proteins) with a low concentration of histamine (1 microM) increased [Ca2+]i from 128 +/- 8 nM to 150 +/- 13 nM (n = 8). When combined, CPA (300 nM) and histamine (1 microM) synergistically raised [Ca2+]i from 134 +/- 6 nM to 607 +/- 61 nM (n = 8). 3. Removal of extracellular Ca2+ (experiments performed in Ca(2+)-free buffer containing 0.1 mM EGTA) had no effect on the synergistic interaction between CPA (300 nM) and histamine (1 microM). 4. The addition of maximal concentrations of CPA (300 nM) and histamine (100 microM) resulted in a rise in [Ca2+]i which was additive when compared to the Ca2+ responses obtained with the two agonists alone. Low (30 nM) and subthreshold (3 nM) concentrations of CPA did not alter the Ca2+ response elicited by maximal concentrations of histamine (100 microM). 5. Subthreshold concentrations of CPA (3 nM) and low concentrations of histamine (1 microM) elicited synergistic rises in [Ca2+]i. 6 Synergistic Ca2+ responses were not observed between histamine Hl- and ATP-receptors when cells were simultaneously stimulated with either 1 microM or 10 microM of each agonist.7 These data suggest that adenosine A1-receptors linked to PTX-sensitive G protein(s) and histamine H14-receptors linked to PTX-insensitive G-proteins interact synergistically to raise [Ca2+]i. In contrast,activation of ATP receptors which are linked to PTX-insensitive G-protein(s) do not interact synergically with histamine H1-receptors. PMID- 8358568 TI - Pharmacology of a cloned potassium channel from mouse brain (MK-1) expressed in CHO cells: effects of blockers and an 'inactivation peptide'. AB - 1. Chinese hamster ovary cells (CHO), maintained in cell culture, were stably transfected with DNA for the MK-1 voltage-activated potassium channel, previously cloned from a mouse brain library. 2. Voltage-activated currents were recorded by the whole cell patch clamp method. In CHO cells transfected with the vector only, there were no significant outward voltage activated currents. However, large outward voltage-activated potassium currents were always observed in those cells which had been transfected with the vector containing the DNA encoding for MK-1. 3. These potassium currents activated from -40 mV, and reversed at the potassium equilibrium potential. The half-maximal conductance of MK-1 was at -10 mV and had a slope factor of 11 mV when fitted with a Boltzmann function. There was only very slight (< 10%) inactivation of MK-1 even at very large positive voltages. 4. MK-1 was reversibly blocked by: 4-aminopyridine (4-AP, 0.1-4 mM), Toxin I 10-100 nM), mast cell degranulating peptide (1 microM), tetraethylammonium (TEA, 4-10 mM), tedisamil (100 microM), quinine (100 microM) and ciclazindol (100 microM); all applied to the outside of the cell from a 'U tube' rapid perfusion system. 4 AP may block closed as well as open MK-1 potassium channels. 5. A synthetic 20 amino acid peptide derived from the N-terminus sequence of the Shaker B potassium channel (the 'inactivation peptide') produced dramatic inactivation of MK-1 when applied to the inside, but not the outside of the cell. Reducing peptide concentration or 'degrading' the peptide produced less inactivation. 6. The block of MK-1 by the synthetic inactivation peptide was quite different in time dependence from block by internal TEA (0.4-4 mM), which probably blocks much more quickly but less potently than the peptide. PMID- 8358569 TI - Differential effects of BQ-123 against endothelin-1 and endothelin-3 on the rat vas deferens: evidence for an atypical endothelin receptor. AB - 1. Endothelin-1 and endothelin-3 enhanced concentration-dependently the rat vas deferens twitch response to electrical stimulation, endothelin-1 being three times more potent. Sarafotoxin S6c was at least 200 times less active than endothelin-1. 2. The response to endothelin was antagonized in a competitive manner by the supposedly selective ETA receptor antagonist, BQ-123 (pA2:7.0 +/- 0.1). In contrast, the endothelin-1 concentration-response curve was only shifted two fold in the presence of 10 microM BQ-123, while no effect was observed at 1 microM. 3. This evidence suggests the rat vas deferens contains an endothelin receptor not conforming to the ETA/ETB receptor subtype classification so far proposed. PMID- 8358570 TI - Protective effects of ranolazine in guinea-pig hearts during low-flow ischaemia and their association with increases in active pyruvate dehydrogenase. AB - 1. In isolated Langendorff-perfused, electrically-paced, hearts of guinea-pigs, global low-flow-ischaemia (LFI; at 0.7 ml min-1) resulted in marked increases in the rates of release of lactate, lactate dehydrogenase (LDH) and creatine kinase (CK) over a 30 min period. At the end of the LFI period, tissue ATP content was significantly reduced from a control value of 11.8 +/- 0.8 (5) to 5.6 +/- 0.8 (5) mumol g-1 dry weight. 2. The presence of ranolazine [(+/-)-N-(2,6-dimethyl phenyl)-4[2-hydroxy-3-(2-methoxy-phenoxyl)- propyl] - l-piperazine acetamide dihydro-chloride; RS-43285-193] at 10 microM, from 20 min prior to and during LFI, resulted in significant reductions in the release of lactate, LDH and CK during the ischaemic period and a significant preservation of tissue ATP (9.0 +/- 1.1 (6) mumol g-1 dry wt.). Ranolazine did not prevent the reductions in creatine phosphate or glycogen observed in LFI, nor did it have any significant effects on any contractile parameters before or during the LFI period. 3. Neither ranolazine nor LFI affected the total amounts of tissue pyruvate dehydrogenase (PDH) activity; however, the significant reduction in the amount of active, non phosphorylated PDH caused by LFI (from 88.2 +/- 5.5 to 44.2 +/- 3.2% of total activity) was partially but significantly prevented by ranolazine (67.2 +/- 6.8%). This effect of ranolazine on PDH may be part of the mechanism whereby the compound reduces lactate release and preserves tissue ATP during ischaemia. PMID- 8358571 TI - Binding of angiotensin antagonists to rat liver and brain membranes measured ex vivo. AB - 1. The effects of the angiotensin antagonists GR117289, losartan and Sar1Ala8 angiotensin II on the ex vivo binding of [125I]-Sar1Ile8-angiotensin II to rat liver and cortex/hippocampus (Cx/H) membranes have been investigated. 2. GR117289 (0.1-30 mg kg-1, s.c., 2 h pretreatment) caused a dose-dependent reduction in [125I]-Sar1Ile8-angiotensin II binding to both liver and cortex/hippocampus membranes. 3. Administration of a submaximal dose of GR117289 (1 mg kg-1, s.c.) indicated that the peak inhibition of binding in the liver occurred within 0.5 h, whereas the peak inhibition of binding in the Cx/H occurred 2 h after drug treatment. 4. The effect of GR117289 was long lasting. Binding was still reduced in the Cx/H 48 h after drug treatment (10 mg kg-1, s.c.) but had returned to normal 72 h after drug treatment. In the liver binding was still reduced 72 h after treatment with the same dose. 5. Losartan (1-30 mg kg-1, s.c.) was equipotent with GR117289 in its ability to reduce liver binding, but was less effective at inhibiting binding to central receptors. 6. The non-peptide antagonist Sar1Ala8-angiotensin II (3 and 10 mg kg-1) reduced binding in the liver but not in the Cx/H membranes. 7. These results suggest that, unlike the peptide antagonist Sar1Ala8-angiotensin II, the non-peptide angiotensin antagonists, GR117289 and losartan, are able to cross the blood brain barrier and occupy central angiotensin II receptors. PMID- 8358572 TI - Effects of rolipram and siguazodan on the human isolated bronchus and their interaction with isoprenaline and sodium nitroprusside. AB - 1 The effects of the selective inhibitors of cyclic AMP phosphodiesterase type IV (rolipram) and type III (siguazodan) and their interactions with isoprenaline and sodium nitroprusside have been studied in the human isolated bronchus. 2 On bronchi under resting tone rolipram was, in terms of potency (pD2 = 7.77 +/- 0.14, n = 8), very similar to isoprenaline (pD2 = 7.31 +/- 0.12, n = 12) and salbutamol (pD2 = 7.12 +/- 0.17, n = 10) and approximately 10 fold more potent than siguazodan (pD2 = 6.80 +/- 0.12, n = 6). In terms of efficacy (Emax, expressed as percentage of maximal effect induced by theophylline 3 mM), both rolipram and siguazodan were less efficient (Emax = 74 +/- 6.7%, n = 8 and 66 +/- 7.5%, n = 6, respectively) than isoprenaline (Emax = 98 +/- 0.4%, n = 12) and salbutamol (Emax = 83 +/- 2.4%, n = 10). 3 During precontraction induced by methacholine (3 x 10(-7) M) or acetylcholine (10(-3) M), concentration-response curves to rolipram and siguazodan were shifted to the right and maximal effects reduced. Rolipram was more potent than siguazodan and, in terms of efficacy, it was less active. 4. Rolipram 10(-8) and 10(-7) M but not siguazodan potentiated the effects of isoprenaline as shown by the shift to the left of the concentration-response curve to isoprenaline. Sodium nitroprusside-induced relaxation was not modified by either drug. 5. These results show that rolipram is a potent relaxant of the human isolated bronchus, potentiating the effects of beta-adrenoceptor stimulation and suggest that, as previously demonstrated in other species(guinea-pig, cow) (Tomkinson et al., 1993), there may be a connection between the beta2-adrenoceptor subtype, which predominate in human airway smooth muscle, and the cyclic AMP phosphodiesterase type IV. PMID- 8358573 TI - Endothelin receptors mediating contraction in goat cerebral arteries. AB - 1. The aim of the present study was to identify the subtype of receptor mediating contraction to endothelin-1 and sarafotoxin S6b in goat isolated middle cerebral arteries. 2. Endothelin-1, endothelin-2 and endothelin-3 contracted cerebral arteries in a concentration-dependent manner. Although the three peptides were full agonists, the order of potency was endothelin-1 = endothelin-2 > endothelin 3, with a relative potency of endothelin-1 and endothelin-2 versus endothelin-3 of approximately 280. Sarafotoxin S6b induced concentration-dependent contractions with lower potency than endothelin-1/endothelin-2, higher potency than endothelin-3 and a higher maximum response than the three endothelins. 3. The selective ETA-receptor antagonist, BQ-123, did not induce changes in either the resting tension or in the active tone developed by depolarization. In contrast, BQ-123 produced concentration-dependent relaxations of endothelin-1 precontracted cerebral arteries, and to a greater extent of sarafotoxin S6b precontracted arteries. 4. Concentration-response curves to endothelin-1 and sarafotoxin S6b were competitively antagonized by BQ-123 (pA2 of 7.43 +/- 0.12 and 8.41 +/- 0.09, respectively). In contrast, BQ-123 had no effect on 5 hydroxytryptamine-elicited contractions even at 10(-6) M. 5. It is concluded that both the order of potency of endothelin isopeptides and the antagonism of BQ-123 point to the existence of ETA receptors mediating vasoconstriction to endothelin 1 and sarafotoxin S6b in the goat middle cerebral artery. The different antagonistic potency of BQ-123 against endothelin-I and sarafotoxin S6b suggests the existence of subtypes of ETA receptors. PMID- 8358574 TI - Hypercholesterolaemia severely impairs EDRF-dependent collateral perfusion following acute arterial occlusion in rabbit isolated ear. AB - 1. We have used a rabbit isolated buffer-perfused ear as a model of acute arterial occlusion to investigate the effects of dietary-induced hypercholesterolaemia on EDRF-dependent collateral perfusion. The effects of hypercholesterolaemia on endothelium-dependent relaxations to acetylcholine were also investigated in the unligated isolated buffer-perfused ear of the rabbit. 2. In rabbits receiving a high cholesterol diet (1%) for 4 weeks, blood cholesterol levels were significantly (P < 0.001) increased (26.0 +/- 3.6 vs. 2.6 +/- 0.6 mmol l-1), EDRF-dependent collateral perfusion was similar to that in age-matched controls for the first 15 min after occlusion but then decreased and was significantly (P < 0.01) less than control during the maintenance phase of collateral perfusion. 3. Cholesterol feeding for 8 weeks (blood cholesterol = 56.2 +/- 3.8 vs. 1.3 +/- 0.1 mmol l-1) was associated with almost complete impairment of collateral perfusion, an effect previously observed following inhibition of EDRF synthesis. 4. Endothelium-dependent relaxations to acetylcholine in isolated perfused ears were impaired in the rabbits fed the diet for 8 weeks but not those fed for 4 weeks. In the 8 week group, the maximum relaxation of tone was 32.6 +/- 11.6% and was significantly (P < 0.01) less than that in the controls (77.9 +/- 5.7%). 5. We conclude that EDRF-dependent collateral perfusion is severely impaired in hypercholesterolaemia and that the level of impairment is related to the duration of feeding. PMID- 8358575 TI - Non-adrenergic, non-cholinergic neural activation in guinea-pig bronchi: powerful and frequency-dependent stabilizing effect on tone. AB - 1. We examined non-adrenergic, non-cholinergic (NANC) stimulation for its stabilizing effect on bronchial smooth-muscle tone with respect to its regulatory power and the effect of variations in neural impulse frequency. 2. The guinea-pig isolated main bronchus (n = 4-12) was pretreated with indomethacin (10 microM) and incubated with atropine (1 microM) and guanethidine (10 microM). Electrical field stimulation (EFS: 1200 mA, 0.5 ms, 240 s) was applied at various levels of tone prior to EFS: first without tone, then at a moderate tone induced by histamine (0.3 microM) and, finally, at a high tone induced by histamine (6 microM). Three different stimulation frequencies (1, 3 or 10 Hz) were used in order to produce moderate to near-maximum contractile and relaxant NANC neural responses. Both the contractile and the relaxant NANC responses were tetrodotoxin sensitive in the guinea-pig isolated main bronchus (3 Hz). 3. Without tone prior to EFS, NANC activation (1, 3 or 10 Hz) induced a pronounced contractile response. At a moderate level of tone prior to EFS, NANC activation induced a less pronounced contractile response. At the highest level of tone prior to EFS, NANC activation induced a relaxant response. All these NANC responses adjusted the tone towards a similar level and this 'stabilization level' was 56(6)% at 1 Hz, 65(3)% at 3 Hz and 56(5)% at 10 Hz, expressed as a percentage of the maximum histamine-induced (0.1 mM) tone in each airway preparation. 4. There was a difference of approximately 90% of maximum between the highest and the lowest tone level prior to NANC activation. This difference was reduced by the converging contractile and relaxantNANC responses and the magnitude of this 'convergence effect' was 40(8)% at 1 Hz, 72(4)% at 3 Hz and 90(2)% at 10 Hz.5. These findings indicate that NANC neural activation stabilizes bronchial smooth muscle tone via a contraction when the tone is low prior to activation and via a relaxation when the tone is high prior to activation. The NANC stabilizing effect on tone appears to be powerful and its magnitude can be controlled by the neural impulse frequency. The level of tone towards which the NANC responses converge does not appear to be markedly altered by variations in the impulse frequency. Our findings are consistent with a regulatory role for NANC responses in the control of bronchial smooth-muscle tone. PMID- 8358576 TI - Antiarrhythmic drugs, clofilium and cibenzoline are potent inhibitors of glibenclamide-sensitive K+ currents in Xenopus oocytes. AB - 1. The novel K+ channel opener, Y-26763 induced outward K+ currents in voltage clamped follicle-enclosed Xenopus oocytes in a concentration-dependent manner with an EC50 value of 58 microM. 2. The Y-26763-induced K+ current was completely and reversibly blocked by glibenclamide (an ATP-sensitive K+ channel blocker) in a concentration-dependent manner (IC50 140 nM). Effects of several antiarrhythmic drugs on Y-26763-induced glibenclamide-sensitive K+ currents were investigated. 3. (+/-)-Cibenzoline, RS-2135, pirmenol, lorcainide and KW-3407 (class I antiarrhythmic drugs, Na+ channel blockers) suppressed Y-26763 responses in a concentration-dependent manner with IC50 values (in microM) of 6.6, 54, 68, 71 and 370, respectively. 4. Clofilium, E-4031, MS-551 and bretylium (class III antiarrhythmic drugs which increase the action potential duration) also suppressed Y-26763 responses concentration-dependently, IC50 values (in microM) were 3.3, 660, 980 and > or = 2000, respectively. N-acetylprocainamide (class III antiarrhythmic drug) scarcely suppressed Y-26763 responses. 5. The glibenclamide sensitive K+ currents elicited by KRN2391 were also suppressed by all these antiarrhythmic drugs. 6. The antiarrhythmic drugs, clofilium and (+/-) cibenzoline block glibenclamide-sensitive K+ channels in Xenopus oocytes at concentrations comparable to their therapeutic plasma levels. PMID- 8358577 TI - Enhancement by endothelin-1 of microvascular permeability via the activation of ETA receptors. AB - 1. The objective of the present experiments was to assess the involvement of endothelin-A (ETA) receptors in mediating the effects of endothelin-1 on microvascular permeability in conscious rats. 2. Bolus injection of endothelin-1 (0.1 and 1 nmol kg-1, i.v.) resulted in a dose-dependent prolonged pressor effect preceded by a transient depressor response. These changes were accompanied by a dose-dependent loss of plasma volume. Endothelin-1 (1 nmol kg-1) enhanced the vascular permeability of the upper and lower bronchi, kidney, stomach, duodenum and spleen (up to 270%) as measured by the extravasation of Evans blue dye. 3. Pretreatment of the animals with the selective ETA receptor antagonist, BQ-123 (1 mg kg-1, i.v.) significantly blunted the pressor response to endothelin-1 without affecting the depressor response. BQ-123 inhibited by 87% the endothelin-1 (1 nmol kg-1)-induced plasma volume loss. BQ-123 markedly attenuated protein extravasation elicited by endothelin-1 in the upper and lower bronchi and kidney, whereas it completely inhibited the permeability effect of endothelin-1 in the stomach and duodenum. BQ-123 by itself had no significant effect on the parameters studied. 4. The endothelin-1 analogue, [Trp(For)21]-endothelin-1, in which Trp21 is formylated, was as potent a pressor agent as endothelin-1, but had no depressor action. Bolus injection of [Trp(For)21]-endothelin-1 (0.1 and 1 nmol kg-1, i.v.) evoked similar plasma volume losses to those observed following administration of equimolar doses of endothelin-1. Furthermore, 1 nmol kg-1 [Trp(For)21]-endothelin-l evoked increases in protein extravasation similar to endothelin-l, 1 nmol kg-1.5. The present findings suggest that endothelin- 1 enhances microvascular permeability, in part, via the activation of ETA receptors. PMID- 8358578 TI - Influence of exercise adherence level on modifiable coronary heart disease risk factors and functional-fitness levels in middle-aged men. AB - The study investigated the potential health benefits of two levels of short-term exercise intervention, compared with non-intervention, on selected modifiable coronary heart disease (CHD) risk factors and functional fitness states in middle aged men. All subjects underwent medical screening and signed informed consent before carrying out a standardized graded treadmill walk which required exercise up to 85% of age-predicted maximal heart rate. The results of the test were used together with musculoskeletal fitness assessments, for the prescription of a personalized exercise programme lasting 14 weeks. In all, 55 subjects were classified by adherence into high (HA, n = 20), low (LA, n = 19), or non adherence (NA, n = 16) groups according to the degree of documented participation in the programme based on standard criteria (American College of Sports Medicine 1978, 1990). In addition, the respective groups of subjects were classified according to other modifiable and non-modifiable CHD risk factors and compared by self-reported levels of activity and sport involvement as well as perceived body weight classification. The results indicated that there were more comprehensive improvements in functional fitness including significant gains in aerobic endurance capacity, muscular endurance and flexibility in the HA group compared with the LA and NA groups. However, there was little or no change in the modifiable CHD risk factors in any of the respective groups, although anthropometric indices of weight, body mass index (BMI), skinfolds and waist:hips ratio tended to decrease in the HA and LA groups but increased marginally in the NA group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358579 TI - Evaluation of the Colin STBP-680 at rest and during exercise: an automated blood pressure monitor using R-wave gating. AB - The application of automated blood pressure measurement during exercise has been limited by inaccuracies introduced by the effects of accompanying motion and noise. We evaluated a newly developed automated blood pressure monitor for measuring exercise blood pressure (Colin STBP-680; Colin, San Antonio, Texas, USA). The STBP-680 uses acoustic transduction with the assistance of the electrocardiogram R-wave to trigger the sampling period for blood pressure measurement. The automated monitor readings were compared with simultaneous technician mercury sphygmomanometric readings in the same arm. Blood pressure was measured in 18 men at rest and during exercise at 40% VO2 peak, (low intensity), 70% VO2 peak (moderate intensity) and VO2 peak (high intensity) on the cycle ergometer. Mean(s.d.) systolic blood pressure difference between the automated monitor and mercury manometer readings at rest and during exercise at low, moderate and high work intensities were 3(0) mmHg, 3(2) mmHg, 1(1) mmHg, and 0(11) mmHg respectively (analysis of variance; P > 0.05). Resting diastolic blood pressure obtained with the STBP-680 was similar to the mercury manometer readings (78(10) versus 81(7) mmHg (P > 0.05). Exercise diastolic pressure at the low level of work intensity was almost identical between the automated monitor and mercury manometer readings (64(8) versus 65(10) mmHg (not significant)). Diastolic blood pressure readings between the STBP-680 and mercury manometer showed a greater difference at the moderate and high workloads (11 mmHg and 9 mmHg, respectively), but this difference was not significant (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358580 TI - Effectiveness of functional ankle taping for judo athletes: a comparison between judo bandaging and taping. AB - This study was conducted to compare the effectiveness of the traditional method of ankle bandaging and the new method of ankle taping for judo athletes in Japan, and to introduce a functionally effective taping method for judo players. Four university judo athletes with ankle instability were selected to undertake radiography of the ankles before and after exercise, with bandaging at one time and taping at the other. Talar tilt (TT) angles were measured in order to compare the ankle-supporting effects. The results showed that the old ankle bandaging method had no role in eliminating the talar tilt during judo practice. In contrast, the new taping method was more effective in eliminating the talar tilt and supporting the involved ankles both mechanically and functionally. PMID- 8358581 TI - Audit of knee injuries seen in a sports medicine clinic. AB - In order to assess the management of knee injuries in a sports medicine clinic, an audit was performed of all new patients who attended the clinic over a 12 month period. Of the 167 new patients seen, 76 (46%) had sustained knee injuries. Of these, 43 (57%) were treated in the sports medicine clinic and 33 (43%) were referred for arthroscopic assessment. The maximum waiting time from the time of referral was 3 weeks, with 85% of patients seen within 1 week and 92% within 2 weeks. Arthroscopy was performed on 28 (85%) of the 33 patients referred, and the positive correlation between the sports clinic diagnosis and the arthroscopic diagnosis was 64%. Of the 33 patients referred for arthroscopy, 28 (85%) had sustained acute knee injuries while five (15%) had been treated at other hospitals before referral to the sports medicine clinic. A National Health Service sports medicine clinic is an effective means of treating knee injuries, provided that access to arthroscopy is readily available. PMID- 8358582 TI - Spinal injuries in sports in the UK. AB - An analysis was made of 150 rugby, trampolining, gymnastics and horse-riding injuries between 1952 and 1985, resulting in severe spinal injury. The individual analyses of the separate sports had been published previously. There are common factors to all these sports. Of those injured 121 had cervical injuries often as a result of participation in sport by young impetuous people, and causes included: inadequate supervision; motivation to attempt tasks beyond their abilities; a mismatch between the abilities of the performer and the task attempted. PMID- 8358583 TI - Surgical treatment of dislocations of the acromioclavicular joint in the athlete. AB - The treatment of the sports related dislocation of the acromioclavicular joint remains controversial. This study was carried out to determine whether or not a combined surgical procedure consisting of repair and polydioxanone (PDS)-cord augmentation of the coracoclavicular ligaments, fixation of the acromioclavicular joint with a single Kirschner wire as well as the repair of the acromioclavicular ligament permitted return to athletic activity. Athletes were examined with regard to their range of motion, pain and their ability to return to the performance level achieved before the injury. During the period 1986-1989, 21 athletes were treated. Follow-up averaged 22 months. Return of athletes to previous performance level was related to their original degree of activity. Two recreational once-a-week athletes did not return to this level, 19 patients, including five competitive athletes, continued their previous activities. There was no correlation between coracoclavicular ossification or post-traumatic arthritis and a good or excellent result. We recommend the operative treatment of acromioclavicular separations in athletes. PMID- 8358584 TI - Shoulder tendinitis and osteoarthrosis of the acromioclavicular joint and their relation to sports. AB - A sample of 207 men from the construction industry was studied using an epidemiological technique of cross-sectional design to investigate if sport activities involving the arms increase the risk of developing shoulder tendinitis or osteoarthrosis of the acromioclavicular joint. The relative risk for shoulder tendinitis was estimated to be 9.5 on the right side, and 4.9 on the left side for a lifetime of sport activity exceeding 8399 h. Subjects who reported both extremely high physical load from work and from sports had an estimated relative risk for signs of shoulder tendinitis of 5.9 on the right side and 10.4 on the left side. High sport activity yielded relative risks of 4.6 on the right side and 2.8 on the left side for osteoarthrosis of the acromioclavicular joint. The combination of high activity in sports and high exposure to load lifted during work yielded relative risks for osteoarthrosis of the acromioclavicular joint of 12.5 on the right side and 6.7 on the left side. There seems to be an increased risk for shoulder tendinitis and acromioclavicular osteoarthrosis for subjects who have been extremely active in sports, and an even higher risk for those who have been extremely active in sports and also report a high exposure to load lifted during work. PMID- 8358585 TI - Patient assessment of treatment following knee injury. AB - A survey of 100 sports-injured cases was carried out to elicit patients' personal assessment of their treatment and to investigate the utility of a typical database system for recording and analysis. The cases were limited to knee injuries, with a high proportion arising from football of various types and interesting light was thrown on several possible contributory factors. PMID- 8358587 TI - Clenbuterol: a medal in tablet form? PMID- 8358586 TI - American football injuries in Finland. AB - American football is currently played in 14 European countries. It is a contact sport where injuries are inevitable. In this study, injuries causing more than one week of absence from game or practise were registered during the 1991 preseason and season. A total of 112 injuries was reported among 684 players. Knees were most vulnerable to injury (28.6%) followed by ankle injuries (16.7%). Operations were performed on 28 (25%) of the injured players. Catastrophic injuries can occur in this sport, but none has happened in Finland during the 12 years for which the sport has been practised. The skill level was not a contributing factor. The frequency of injuries and their profile closely resemble those in US-based studies so it is suggested that the precautions and preventive measures recommended in the USA should be applied and followed in Europe. PMID- 8358588 TI - Hong Kong Sports Institute: sports medicine and science from theory to practice. PMID- 8358589 TI - Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. PMID- 8358590 TI - Arthrography and arthrotomy of the knee in sports injuries. AB - A total of 266 patients with injuries to the knee sustained during sports activities were managed by arthroscopy and/or arthrotomy. All of them received systemic examination and a standard battery of knee stability tests. Fifty-three were examined by arthrography and all underwent arthrotomy for surgical correction of the lesion diagnosed by both clinical examination and arthrography. Our study showed that clinical examination could give an accurate clinical diagnosis in 88.35% of cases and arthrography in 76.89%. No complication from arthrography was found. Injury occurred most commonly between 21 and 30 years of age and was more common to the right knee than the left. The sport in which most injuries occurred was football. PMID- 8358591 TI - Closed extensor tendon rupture and distal radial fracture with use of a gymnast's wrist support. AB - We report a case of delayed closed rupture of the tendon of extensor indicis proprius in a skeletally immature individual. This occurred following a minor greenstick fracture during use of a gymnast's wrist-finger support. To our knowledge this unusual complication has not been described previously. PMID- 8358593 TI - Speech perception and brain laterality: the effect of ear advantage on auditory event-related potentials. AB - Dichotic listening has been used for assessing asymmetries in processing auditory stimuli. It is known that there is better recognition of dichotic stimuli in the right ear with verbal stimuli (right ear advantage, REA) by the majority of the subjects. We were interested in the psychophysiological correlates of ear advantage as it is manifested in event-related potentials (ERP). We compared ERPs to monaural and dichotic syllables in stable REA and LEA subjects. The most consistent finding was that REA subjects show larger positive ERP deflections over the left hemisphere (maximal at T5) and LEA subjects over the right hemisphere (maximal at T6) both at the latency range of 320-340 msec. Thus, brain event-related potentials support the contention that the REA and LEA reflect differential activation of the left and right hemispheres, respectively. PMID- 8358592 TI - Sports medicine: some ethical issues. AB - The ethical aspects of sports medicine have hitherto received little scrutiny, in contrast to its legal implications, which have recently been subject to much greater discussion. However, the differences that are apparent between sports medicine and 'mainstream' areas of clinical practice can shed new light on a number of the central issues within health-care ethics. By means of hypothetical case studies, this paper seeks to examine some of these issues within a sports medicine context. Specific attention will be paid to the concepts of autonomy and paternalism, issues to do with truthfulness, and the question of conflicting professional loyalties. It is suggested that the ethics of sports medicine warrant further and more detailed examination. PMID- 8358594 TI - Automatic access to lexical semantics in aphasia: evidence from semantic and associative priming. AB - We report the auditory lexical decision performance of four patients, all of whom are clinically diagnosed as Broca's aphasics. In a task that separates associative from semantic priming, all four patients show significant priming effects and no interaction with type of relatedness. We find no evidence to support some of the current accounts of these patients' linguistic difficulties in terms of an impairment in automatic processing routines. Instead, we argue that automatic access to lexical semantics is intact. PMID- 8358595 TI - Intraword timing relations in Thai after unilateral brain damage. AB - The present study examined temporal characteristics of monosyllabic, bisyallabic, and trisyllabic words in Thai to evaluate timing control at the word level in brain-damaged patients. Subjects included young and old normal adults, right hemisphere patients, and left hemisphere nonfluent and fluent aphasic patients. Utterances were produced at a conversational speaking rate. Results indicated that, on an absolute or relative measurement scale, magnitude of the shortening effect on nonfinal syllables in polysyllabic words was significantly smaller in left nonfluent aphasics than in other groups. In trisyllabic words, duration of the penultimate syllable for left fluent aphasics was also significantly longer than that of normals. Left nonfluent and fluent aphasics were significantly more variable than other speakers in their production of bisyllabic and trisyllabic words. Findings are discussed in relation to issues pertaining to the nature of timing deficits in nonfluent and fluent aphasic patients. PMID- 8358596 TI - Diazepam therapy of verbal auditory agnosia. AB - A 7-year-old girl suffered from a gradual loss of her ability to understand speech. But she had normal hearing and understood various environmental sounds. Brain computerized axial tomography showed normal, but electroencephalogram revealed spike and wave activity from temporal leads, especially on the left side. She was diagnosed as having verbal auditory agnosia. The treatment consisted of diazepam therapy. One year after the onset, her impaired auditory comprehension dramatically improved with the use of diazepam. The dichotic listening test revealed a left ear advantage for both environmental sounds and spoken words. The results seemed to suggest that in this patient the right hemisphere might be functioning as a speech center instead of the left one. PMID- 8358597 TI - Impairments of lexical-semantic processing in aphasia: evidence from the processing of lexical ambiguities. AB - Broca's and Wernicke's aphasics performed speeded lexical decisions on the third member of auditorily presented triplets consisting of two word primes followed by either a word or a nonword. In three of the four priming conditions, the second prime was a homonym with two unrelated meanings. The relation of the first prime and the target with the two meanings of the homonym was manipulated in the different priming conditions. The two readings of the ambiguous words either shared their grammatical form class (noun-noun ambiguities) or not (noun-verb ambiguities). The silent intervals between the members of the triplets were varied between 100, 500, and 1250 msec. Priming at the shortest interval is mainly attributed to automatic lexical processing, and priming at the longest interval is mainly due to forms of controlled lexical processing. For both Broca's and Wernicke's aphasics overall priming effects were obtained at ISIs of 100 and 500 msec, but not at an ISI of 1250 msec. This pattern of results is consistent with the view that both types of aphasics can automatically access the semantic lexicon, but might be impaired in integrating lexical-semantic information into the context. Broca's aphasics showed a specific impairment in selecting the contextually appropriate reading of noun-verb ambiguities, which is suggested to result from a failure either in the on-line morphological parsing of complex word forms into a stem and an inflection or in the on-line exploitation of the syntactic implications of the inflectional suffix. In a final experiment patients were asked to explicitly judge the semantic relations between a subset of the primes that were used in the lexical decision study. Wernicke's aphasics performed worse than both Broca's aphasics and normal controls, indicating a specific impairment for these patients in consciously operating on automatically accessed lexical-semantic information. PMID- 8358598 TI - Anomia for facial expressions: neuropsychological mechanisms and anatomical correlates. AB - We report a patient with a selective impairment in naming and pointing to emotional facial expressions following a circumscribed lesion of the right temporal lobe. Detailed investigation of this patient's deficit revealed that the neuropsychological mechanism underlying his anomia for facial expressions is best understood as a category-specific bidirectional visual-verbal disconnection between intact visual semantic and verbal semantic representations for facial emotions. Magnetic resonance imaging findings from this case and from another patient previously described with this unique syndrome (Rapcsak, Kaszniak, & Rubens, 1989), together with the results of cortical electrical stimulation studies and microelectrode recordings of cortical neuronal activity in epileptic patients, provide converging evidence that the inferotemporal visual association cortex of the right middle temporal gyrus plays an important functional role in the verbal labeling of emotional facial expressions. The implications of these findings for cognitive and neural models of facial affect processing are discussed. PMID- 8358600 TI - An investigation of attention allocation deficits in aphasia. AB - Nine aphasic and 18 normal adults participated in a dual task with components of phoneme monitoring and semantic judgment. Subjects listened to lists of recorded spoken words and were required to detect semantic and phonetic targets. Two within-subject variables were manipulated: the probability of target occurrence for each dual-task component (.2, .5, and .8) and the explicitness of instruction (explicit vs. implicit). Only in the explicit condition were subjects told about the probability structure and given the attention allocation strategy congruent with that structure. Reaction times were recorded on-line for analysis by an IBM AT. The results showed that normal subjects' overall latencies in detecting phonetic targets decreased as the target occurrence probability increased in both implicit and explicit instruction conditions. The detection latencies for semantic targets showed a similar probability effect but only in the explicit condition. By contrast, the aphasic subjects did not show the probability effect in any condition, although they performed above the chance level on both semantic and phonetic tasks. The presence of the probability effects for the normal subjects indicated that an efficient attention allocation mechanism was operating so as to optimize the performance level. On the other hand, the absence of probability effects for the aphasic subjects suggests that their attention control system might be inefficient so that task-demand cues (probability and attention allocation instruction) were not utilized properly. PMID- 8358599 TI - Memory impairment and executive control in individuals with stroke-induced aphasia. AB - The purpose of this study was to examine memory abilities of aphasic individuals in relation to site of neurological lesion. Fourteen individuals with stroke induced aphasia (7 with anterior lesions; 7 with posterior lesions) and 14 demographically matched control subjects were given selected tests of short-term memory (STM) and long-term memory (LTM). Stroke patients were impaired relative to control subjects on tests of verbal memory, with greater impairment of LTM associated with anterior lesions and greater impairment of STM associated with posterior lesions. Verbal memory performance did not correlate highly with language ability, and did not appear to be simply a consequence of language impairment. Executive control deficits were postulated as explanatory of the LTM impairment associated with anterior lesions. PMID- 8358601 TI - Blunting of the neurotensin mRNA response to haloperidol in the striatum of aging rats: possible relationship to decline in dopamine D2 receptor expression. AB - Neuroleptic drugs such as haloperidol (H) induce a rapid increase in neurotensin/neuromedin N (NT/N) gene expression in the dorsolateral striatum (DLSt) and nucleus accumbens (NA) in young adult rats. This effect may be mediated by post-receptor effectors that are activated by dopamine D2 receptor antagonism. The regional pattern of induction of neurotensin gene expression correlates with the side effect profile of particular neuroleptics. As motor side effects of H differ in aged animals, we hypothesized that the regional expression of the neurotensin gene may differ between young and old animals. We administered H or saline acutely to 3, 14, and 25 month-old Fischer 344 rats, followed by in situ hybridization and quantitative autoradiography for NT/N mRNA. There was a significant age effect on the H-induced NT/N mRNA response in the DLSt, but not the NA, of older animals. In addition to the blunted NT/N mRNA response, significant decreases in D2 receptor mRNA were observed in the lateral striatum of another group of young, middle-aged, and aged rats. Age-related blunting of the NT/N mRNA response to H in the DLSt may be due in part to a decrease in D2 receptors in this structure. PMID- 8358602 TI - Intracerebroventricular administration of corticotropin-releasing factor induces c-fos mRNA expression in brain regions related to stress responses: comparison with pattern of c-fos mRNA induction after stress. AB - Centrally administered corticotropin-releasing factor (CRF) produces a number of physiological and behavioral changes akin to those elicited by exposure to acute stress. However, the specific brain site of action responsible for the centrally activating property of CRF has not been precisely determined. In this study, we used in situ hybridization histochemistry for c-fos mRNA to map potential neuronal structures activated after intracerebroventricular (i.c.v.) injection of CRF and compared the distribution of c-fos mRNA with that after stress. Wistar male rats were sacrificed 30, 60, 120 and 180 min after the i.c.v. injection of 1 microgram ovine CRF or vehicle alone. Another group of rats was exposed to immobilization stress for 60 min or electrical foot-shock stress (1.5 mA, 1-s duration, 30 x) for 15 min and sacrificed before and 30, 60, 120 and 180 min after the beginning of stress. Centrally administered CRF rapidly (30-60 min) induced c-fos mRNA expression in most of the areas that showed hybridization signals for c-fos after stress: the limbic structures, including the piriform cortex, cingulate cortex, the lateral septal nucleus, the hippocampus, the anterior corticomedial and the medial amygdaloid nuclei, the hypothalamic nuclei, such as the paraventricular nucleus, the supraoptic nucleus (SO) and the dorsomedial nucleus (DMD), and some brainstem nuclei like the pontine nucleus, the locus ceruleus (LC) and Barrington's nucleus. The granular layer of the cerebellum, some thalamic nuclei and the habenula also showed hybridization signals after i.c.v. injection of CRF and stress. However, c-fos induction in the bed nucleus of the stria terminalis, the central nucleus of the amygdala (CeA) and the nucleus tractus solitarius (SOL) was seen only after i.c.v. administration of CRF; in the septo-hypothalamic nucleus and the superior olive, however, c-fos mRNA expression was observed only after stress. There were no differences in the pattern of c-fos mRNA expression between the two stress paradigms. In contrast, i.c.v. injection of saline-induced expression of c-fos mRNA in the piriform cortex, neocortex, cingulate cortex and the amygdala was much less than that seen after i.c.v.-administered CRF as evident in the intensity of the signals. These results suggest that CRF produces c-fos mRNA expression in the brain areas related to stress response, and that CRF may induce behavioral and neuroendocrine responses through activating these brain structures, such as the limbic system and the hypothalamic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8358604 TI - Olfactory sensitivity of rats with transection of the lateral olfactory tract. AB - Rats with discrete transection of the lateral olfactory tract (LOT) were tested using operant conditioning and psychophysical methods for their amyl acetate intensity difference threshold and absolute detection threshold. Experimental rats performed as well as controls on the easiest problems of both threshold series but their intensity difference threshold was approximately 2.5 times as high as controls and their absolute detection threshold was approximately 2.25 orders of magnitude higher than controls. The deficit in sensitivity in both tests was related to the frontal level at which the tract was cut; rats with the most rostral transection had the greatest increase in threshold. The absolute detection threshold of rats with transection of the LOT was increased to that of normal human subjects tested with the same apparatus. PMID- 8358603 TI - Neurobehavioral changes produced in rats by prenatal exposure to carbon monoxide. AB - Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) produced a significant reduction in the minimum frequency of ultrasonic calls emitted by rat pups removed from their nest. Moreover, a significant decrease in the responsiveness (rate of calling) to a challenge dose of diazepam (0.25 mg/kg) was found in male pups exposed to CO (150 ppm) during gestation. Prenatal CO (75 and 150 ppm) did not significantly affect locomotor activity or D-amphetamine-induced hyperactivity in both 14- and 21-day-old animals. Furthermore, adult male rats exposed to this chemical (150 ppm) during gestation exhibited significant alterations in the acquisition of an active avoidance task. CO-induced learning disruption does not seem to be linked to changes in the emotionality of animals. These findings suggest that gestational exposure to CO induces in rat offspring both short- and long-term behavioral changes characterized by altered ontogeny of emotional responsiveness to environmental challenges and by learning impairment. PMID- 8358605 TI - NMDA glutamatergic receptors, labelled with [3H]MK-801, in brain samples from drug-free depressed suicides. AB - Glutamate receptors of the NMDA-subtype were quantitated by binding of [3H]dizocilpine maleate (MK-801) in nine brain regions from 22 suicide victims (20-60 yr), with a firm retrospective diagnosis of depression, who had not recently received antidepressant drugs, and 20 age- and sex-matched controls. [3H]MK-801-binding did not differ between suicides and controls in any region studied. Suicides who died violently did not differ from non-violent suicides and controls. A significative negative correlation was found between age and NMDA receptor-binding in the frontal cortex of suicide victims, but not in controls. This preliminary study provides little evidence for an important role of NMDA binding sites in the pathophysiology of depression. PMID- 8358606 TI - Influence of GABA on neurons of the gustatory zone of the rat nucleus of the solitary tract. AB - The role of gamma-aminobutyric acid (GABA) as an inhibitory neurotransmitter in the rostral, gustatory zone of the nucleus of the solitary tract (rNST) was examined using whole cell recordings in brain slices of the adult rat medulla. Superfusion of GABA resulted in a concentration-dependent reduction in input resistance in 68% of the neurons in rNST. The change in input resistance was often accompanied by membrane hyperpolarization. The effect of GABA was a direct action on the postsynaptic membrane since it could be elicited when synaptic transmission was blocked by tetrodotoxin or in a low Ca2+ and high Mg2+ perfusing solution. The mean reversal potential of the GABA effect was about -60 mV, determined by applying GABA at different holding potentials, or from the intersection of current-voltage curves measured in control saline and saline containing GABA. When neurons were separated into groups based on intrinsic membrane properties, some neurons in each group responded to GABA. Superfusion of the slices with either the GABAA agonist, muscimol, or the GABAB agonist, baclofen, caused a decrease in input resistance accompanied by membrane hyperpolarization. The GABAA antagonist bicuculline either totally or partially blocked the neuronal response to GABA and blocked the response to muscimol but did not antagonize responses to baclofen. Superfusion of the GABAB antagonist phaclofen depressed the membrane responses to GABA. The use of the GABAA and GABAB agonists and antagonists demonstrates that some neurons in rNST have both GABAA and GABAB receptors. Since most rNST neurons studied respond to GABA, inhibition probably plays a major role in sensory processing by the rNST. PMID- 8358607 TI - Mesencephalic microinjections of neurotensin-(1-13) and its C-terminal fragment, neurotensin-(8-13), potentiate brain stimulation reward. AB - Using the curve shift method, we assessed the effects of ventromedial mesencephalic tegmental (VMT) microinjections of an equimolar concentration of neurotensin-(1-13) (NT-(1-13)) and of its C-terminal fragment, neurotensin-(8-13) (NT-(8-13)), on operant responding for rewarding electrical stimulation of the caudal mesencephalic central gray. The effects of NT-(1-13) and NT-(8-13) on brain stimulation reward (BSR) were also compared to those of systemically administered quinpirole (0.1 and 0.2 mg/kg, s.c.), a direct dopamine agonist, and GBR-12909 (10 and 20 mg/kg, i.p.), a selective dopamine uptake blocker. At the concentration injected, NT-(8-13) was as effective as NT-(1-13) at facilitating BSR, producing significant leftward shifts of the function relating the rate of responding to the stimulation frequency (R/F function); neither form of the peptide was effective when injected in regions dorsal to the VMT. Similarly, GBR 12909 produced a parallel leftward shift of the R/F function, but, unlike NT-(1 13), also significantly increased the asymptotic rates of responding. In contrast, the high dose of quinpirole produced non-parallel leftward shifts of the R/F function and suppressed the asymptote. The similarity between the effects of neurotensin and GBR-12909 on one hand, and the differences between those of neurotensin and quinpirole on the other, suggest that activation VMT neurotensin receptors potentiate BSR by enhancing increases in dopamine neurotransmission that are contingent upon operant responding or rewarding brain stimulation, or both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358608 TI - Polyamines modulate the neurotoxic effects of NMDA in vivo. AB - The ability of polyamines to alter NMDA-induced neurotoxicity in neonatal rats was examined to determine whether polyamines modulate NMDA receptor activity in vivo. Unilateral injections of NMDA and/or polyamines were made into the striatum of 7-day-old rats. After 5 days, the brains were removed and 20 microns thick coronal sections were cut and stained with Cresyl violet. A computer-based image analysis system was used to densitometrically measure the cross-sectional area of intact tissue in the control and injected hemispheres. Administration of NMDA (5 40 nmol) produced a dose-dependent tissue damage that ranged from 7 to 52% of the area of the uninjected hemisphere. The polyamine agonist spermine (10-500 nmol) dose-dependently exacerbated the toxicity of a 15 nmol dose of NMDA, increasing the size of the lesion by up to 50%. Administration of spermine alone produced dose-dependent tissue damage that ranged from 9 to 52%. The damage produced by both NMDA and spermine could be completely inhibited by co-administration of the NMDA antagonist MK-801. The polyamine inverse agonist 1,10-diaminodecane (DA-10, 50-400 nmol) inhibited the damage produced by NMDA in a dose-dependent manner, with a maximal inhibition of 50%. Administration of DA-10 alone produced limited damage at doses above 100 nmol. The weak partial agonist diethylenetriamine had no effect by itself or on NMDA-induced toxicity at the doses tested. These results indicate that polyamines can modulate the activity of NMDA receptors in vivo and suggest that polyamines or related compounds may have important therapeutic potential as neuroprotective agents. PMID- 8358609 TI - Kindling antagonism: mapping of susceptible sites. AB - Previous research has shown that concurrent alternating stimulation of paired limbic sites culminates in kindling of generalized seizures from 1 (dominant) site, whereas the other (suppressed) site supports only focal or partial seizures. This phenomenon has been referred to as kindling antagonism, and it has been proposed that antagonism reflects an arrest of kindling, which is therefore viewed as a non-continuous stepwise process. We have attempted to replicate these important observations in adult rats stimulated in various combinations of forebrain sites. Kindling antagonism was displayed by rats stimulated in the amygdala and the septal area, in the bilateral amygdala, the septal area and the splenium of the corpus callosum, and the amygdala and the cingulate cortex. We also found that antagonism between the amygdala and septal area as well as electrographic and behavioral correlates of alternating stimulation were sensitive to the hemispheric relation of the electrodes and to the order in which the sites received initial stimulations. That is, rats that carried ipsilateral amygdaloid and septal electrodes were less likely to display antagonism when the amygdala was the first site stimulated. On the other hand, we failed to obtain antagonism from rats stimulated in other limbic pairs (e.g. entorhinal cortex and septal areas. PMID- 8358610 TI - Mechanical hyperalgesia in streptozotocin-diabetic rats is not sympathetically maintained. AB - It has been suggested that the mechanism underlying the pain that occurs in patients with diabetic neuropathy may be similar to that mediating sympathetically maintained pain (SMP), such as occurs in patients with reflex sympathetic dystrophy. To evaluate this suggestion we have examined a model of diabetes mellitus, the streptozotocin-diabetic (STZ-D) rat, for features characteristic of SMP. We demonstrate that the decrease in nociceptive threshold observed in the STZ-D rat is not attenuated by chemical sympathectomy nor exacerbated by intradermal injection of norepinephrine (NE). In addition, the NE content is markedly decreased in the skin of the STZ-D rat. These results suggest that altered nociceptive thresholds associated with diabetic neuropathy are not sympathetically maintained. PMID- 8358611 TI - Neuronal loss in the human claustrum following ulegyria. AB - The claustrum is a large subcortical structure that in animals possesses extensive connections with almost all regions of the cerebral cortex. Because there are no data that support the presence of claustrocortical connections in human brain, the main aims of the present study were to confirm the existence of these connections in the human brain. Five control brains and nine brains with bilateral and large ulegyria were studied. Severe neuronal loss in the anterior part of the claustrum was observed after pathological lesions that involved the frontal cortex. Pathological changes localized in the parietal and occipital cortices caused neuronal loss in the central and posterior part of the human claustrum. These findings suggest that the human claustrum is dependent on the neocortex and that, as in animals, it possesses extensive connections with the cerebral cortex that are topographically organized. The anterior part of the claustrum is connected with the frontal cortex, and the central and posterior parts with the parietal and occipital cortices. PMID- 8358612 TI - Abdominal vagal afferents excite A1 area neurons antidromically activated from the region of the supraoptic nucleus in the rabbit. AB - We made extracellular recordings from 113 spontaneously active neurons in the A1 area, after identifying the cells by antidromically activating them from the region of the supraoptic nucleus in urethane-anesthetized rabbits. We tested the response of these neurons to inputs from abdominal vagal, renal and somatic nerves. Electrical stimulation of the abdominal vagus nerve activated 64/85 neurons tested (75%), and had no effect on the remaining 25%. Latency was 195 +/- 25 ms, (conduction velocity 0.7 m/s). Stimulation of renal afferents had no effect on the discharge rate of 4 neurons tested. Stimulation of branches of the sciatic nerve inhibited 7/17 A1 area neurons tested, excited 4 and had no effect on 6 neurons. Stimulation of the central ear nerve inhibited 4/17 neurons tested, excited 6 and had no effect on 7 neurons. Gastric distension had no effect on 20/24 neurons tested. Lightly touching the animals back and legs had no effect on the discharge of 45/49 neurons tested. Similarly, painful stimuli failed to affect 44/49 neurons tested. Our results indicate that A1 area neurons, with projections to the region of the supraoptic nucleus, receive excitatory inputs from the abdominal vagus nerve. The visceral information transmitted to A1 cells by these abdominal vagal afferents is not yet determined, but acute gastric distention does not appear to be a physiological stimulus. A1 area neurons seem not to be involved in transmitting somatic information to the hypothalamus. PMID- 8358613 TI - In Aplysia sensory neurons, the neuropeptide SCPB and serotonin differ in efficacy both in modulating cellular properties and in activating adenylyl cyclase: implications for mechanisms underlying presynaptic facilitation. AB - The facilitatory transmitters serotonin (5-HT) and the molluscan neuropeptides SCPA and SCPB both activate adenylyl cyclase in Aplysia mechanosensory neurons and produce multiple modulatory effects that contribute to increasing transmitter release from these cells. This enhancement of transmitter release from sensory neurons contributes to increased behavioral response during sensitization and classical conditioning in Aplysia. Recently, specific examples of modulation in these sensory neurons have been described that are more effectively initiated by 5-HT than by the SCPs. For example, in the present study, 5-HT produces 55% greater broadening of the normal sensory neuron action potential than did SCPB. These differences in the modulatory actions of the facilitatory transmitters have been interpreted as suggesting that 5-HT produces its modulatory effects at least partly via a cAMP-independent mechanism. However, we have found that the two types of facilitatory transmitters are not equally effective in activating adenylyl cyclase. In both whole CNS membranes and sensory neuron membranes, SCPB was less effective than 5-HT in stimulating adenylyl cyclase activity measured in steady state assays. Because electrophysiological experiments suggested that the response to the SCPs desensitizes rapidly, we further compared cyclase stimulation in perfused membrane assays that enable continuous monitoring of cyclase activity; however we observed that 5-HT was also more effective than SCPB in stimulating cyclase at the onset of transmitter exposure. We discuss the possibility that lower peak stimulation of cyclase by SCPB and a faster rate of desensitization could account for some of the differences between the SCPs and 5 HT in modulating sensory neurons. PMID- 8358614 TI - Separate neural pathways respond to different noxious stimuli affecting respiratory pump frequency in Aplysia fasciata. AB - Neural circuits responsible for both conditioned and unconditioned respiratory pumping to three stimuli modulating respiratory pumping were examined. The stimuli used were: (i) reduction of pH; (ii) increase and (iii) decrease in seawater concentration. Ablation of the osphradium, but not of the rhinophores, abolished responses to all 3 stimuli. Cutting the pleural-abdominal connectives led to a decrease in responses to lowered pH, but did not affect responses to changes in seawater concentration. Further lesions showed that integrity of the cerebral-pleural ganglion is needed for animals to respond to a decrease in pH. Thus, neural circuitry entirely within the abdominal ganglion and the periphery innervated by the ganglion is sufficient for mediating responses to changes in seawater concentration, while the cerebral ganglion is needed to respond to lowered pH. Different transmitter mechanisms are also used by pathways responding to changes in seawater concentration and to decreased pH: 5,7-dihydroxytryptamine in concentrations which cause depletion of serotonin blocked the response to lowered pH, but not to altered seawater concentrations. PMID- 8358615 TI - Demonstration of a human urinary trypsin inhibitor (urinastatin)-like substance in the murine brain. AB - A human urinary trypsin inhibitor (urinastatin)-like immunoreactive substance with trypsin-inhibitory activities was found in the murine brain. Regional levels of this urinastatin (UT)-like substance in the brain were within 5 ng/mg protein and were expressed in a descending order as follows: cerebral cortex not equal to hippocampus > hypothalamus > mesencephalon not equal to corpus striatum >> medulla oblongata > cerebellum. Mechanical lesioning of the cerebral cortex or hippocampus with a needle induced a rapid and intense appearance of a UT-like immunoreactive substance in the neuronal cells of injured sites. Conditioned fear stress induction incited a reversible increase in the level of UT-like immunoreactive substance in the hippocampus. These results suggest that the UT like immunoreactive substance is produced by neurons in response to brain injury and fear-stress stimuli. PMID- 8358616 TI - Heterogeneous distribution of D1, D2 and D5 receptor mRNAs in monkey striatum. AB - The primate striatum has a compartmental organization reflected both in the topography of its afferent projections and in the segregation of its morphologically similar but neurochemically distinct efferent neurons. Discretely projecting mesostriatal neurons release dopamine (DA) which modulates the responses of striatal neurons to other afferent inputs. Multiple DA receptor (DAR) subtypes have been cloned and characterized and mapping their cellular expression is crucial for understanding the influence of DA on striatal function. We report the distribution of mRNAs for D1, D2 and D5 DAR subtypes (D2R, D2R and D5R) in the striatum of cynomolgus monkeys (Macaca fascicularis) studied by in situ hybridization histochemistry (ISH) using monkey-specific cRNA probes. Adjacent sections were stained for calbindin immunoreactivity to distinguish striosomal and matrix compartments for comparison with the patterns obtained with ISH. In the caudate nucleus, D1R mRNA was concentrated in calbindin-poor striosomes where dense grain clusters were seen overlying the majority of medium sized neurons (diameter approximately 15 microns). D1R mRNA localization was relatively homogeneous in the putamen. By contrast, the distributions of D2R and D5R mRNAs showed no clear preference for the striosomal or matrix compartments of either caudate nucleus or putamen. In the ventral striatum (nucleus accumbens, olfactory tubercle and ventral portions of caudate nucleus and putamen), expression of D1R and D2R mRNA was sparse relative to dorsal striatum, while D5R mRNA expression was roughly equal in ventral and dorsal striatum. Circumscribed zones of hybridization associated with islands of tightly packed small cells occurred with all three DAR mRNA subtypes in the ventral striatum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358617 TI - Suppression of visual responses of neurons in inferior temporal cortex of the awake macaque by addition of a second stimulus. AB - The responses of neurons, in inferior temporal cortex of the awake macaque, to single stimuli and pairs of stimuli were examined. The responses of most neurons were weaker to pairs of stimuli than to the best single stimulus of that pair presented alone. This 'suppression by a second stimulus' did not appear to be stimulus-selective and the suppression was greater when the second stimulus appeared in receptive field locations that exhibited weaker responses. This phenomenon suggests competitive interactions between IT neurons that may be involved in visual attention or learning or both. PMID- 8358618 TI - Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study. AB - Neuroanatomical methods were used to determine if cocaine irreversibly injures neurons. Despite acute and chronic high-dose treatments for months that produced stereotyped behavior and seizures, and the use of a sensitive silver impregnation method, we were unable to find any evidence of neuronal damage anywhere in the brain. Since expression of the inducible 72 kDa heat shock protein (HSP72) is a sensitive indicator of potentially toxic neuronal stress, we next determined if cocaine evoked HSP72 expression. Even high doses of cocaine that evoked seizures did not induce HSP72 immunoreactivity anywhere within the brain, whereas kainic acid produced widespread HSP72 immunoreactivity and irreversible injury. Having failed to find indications of frank neurotoxicity, we examined peptide and protein cell marker immunoreactivities in search of cocaine-induced changes. Although cocaine treatment had no obvious effects on the patterns of hippocampal calbindin-D28K, somatostatin-, tyrosine hydroxylase- and parvalbumin immunoreactivities, cocaine reliably altered neuropeptide Y-like immunoreactivity (NPY-LI). Most notably, NPY-LI was expressed in hippocampal dentate granule cells and pyriform cortical neurons, which do not normally express it. Conversely, we noted decreased NPY-LI in dentate hilar neurons that normally do express it. Since both changes in NPY-LI were seen only in cocaine-treated rats that exhibited seizures, the role of seizure activity per se in producing the NPY changes was addressed in normal rats by electrical stimulation of the perforant path. Like cocaine, perforant path stimulation for as little as 15min evoked NPY LI in granule cells but did not replicate the cocaine-induced decrease in hilar cell NPY-LI. These results suggest that cocaine does not irreversibly injure neurons in the rat, even at doses that induce seizures. However, cocaine produces long-lasting changes in NPY expression that are of unknown functional significance. Our inability to demonstrate cocaine-induced neuronal damage in rats should in no way be taken as evidence of its safety in humans. PMID- 8358619 TI - Task constraints on foot movement and the incidence of compensatory stepping following perturbation of upright stance. AB - Our understanding of the postural control responses in the event of external perturbation has focused almost exclusively on the early automatic adjustments. The present study addresses another postural reaction that is functionally important: compensatory stepping. The purpose was to identify the relative importance by comparing the prevalence of compensatory stepping with and without instructions constraining the subjects' responses. Subjects stood on two force plates which were mounted on a "moveable" platform. Their posture was perturbed by the translation of the platform either forward or backward at various accelerations. Following a practice period, seven subjects each performed under two different tasks: "constrained" (keep feet in place) and "unconstrained" (no specific instructions given). The primary focus of the analysis was on responses to forward platform translations. Analysis revealed that the frequency of stepping tended to be higher in "unconstrained", as opposed to "constrained", tasks. The frequency of stepping was also related to the interaction between the tasks and the order in which they were given. Specifically, subjects stepped most frequently when they received the "unconstrained" task first. The frequency of stepping also increased as the magnitude of the platform acceleration increased. Time of onset of stepping, as defined from the force plate measures, began as early as 160 ms in one subject and averaged 250 ms across all subjects. These relatively fast response times suggest that step initiation often occurs well before the limits of stability are reached. A novel and unexpected finding was the identification of a third response type, intermediate to stepping and (bilaterally symmetrical) non-stepping responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358620 TI - Separation of different interictal discharge patterns in acute experimentally induced epileptic foci of the rat in vivo. AB - Epileptic discharge patterns in an acute experimental model of epilepsy were analyzed. Epileptic foci were induced by epicortical application of penicillin on the rat motor cortex in vivo. Patterns with regular 1/s discharges, patterns with irregular discharges of about 0.5/s as well as compound patterns comprising discharges with intervals of about 300 ms could be differentiated by means of interval histograms and autocorrelation functions. These patterns occurred in an ordered sequence indicating that the different rhythms are activated by a progressive enlargement of the focus and duration of focal activity. The experiments suggest that different interictal discharge patterns can occur within the same brain regions and are not specific for a certain etiology; instead they seem to represent 'resonance' frequencies characteristic for the brain tissue which are disclosed under pathophysiological conditions. PMID- 8358621 TI - Medial diencephalic sites involved in calcitonin-induced hyperthermia and analgesia. AB - Calcitonin is a peptide hormone which can act centrally to decrease food intake and locomotor activity, and increase body temperature and nociceptive thresholds. In a previous study we showed that the brain sites involved in the food intake and locomotion decreases were mostly the paraventricular nucleus, the perifornical area and the preoptic area above the optic chiasma. We now study the diencephalic sites involved in calcitonin-induced increases in body temperature and nociceptive thresholds. Salmon calcitonin (15 ng in 0.3 microliters) was injected in several diencephalic sites, and the effects on body temperature and nociceptive thresholds compared with a saline injection. The results show that the sensitive sites are the dorsomedial nucleus of the hypothalamus, the preoptic area and the centromedial nucleus of the thalamus, and not the paraventricular nucleus and adjacent perifornical area. Therefore, different kinds of central effects of calcitonin can be differentiated on an anatomical basis. PMID- 8358622 TI - Neonatal glutamate can destroy the hippocampal CA1 structure and impair discrimination learning in rats. AB - Neonatal Wistar rats were subcutaneously injected with 0.1, 1, or 2 mg/g b.wt. of monosodium glutamate (MSG) at 1, 3, 5, 7, and 9 days after birth. The animals were observed for degeneration of pyramidal cells in the hippocampus. The histological change disappeared when the animals were concurrently injected with glutamate diethyl ester (GDEE), an antagonist of the glutamate receptor. When light-dark discrimination learning was carried out at 10 weeks old, the correct response in the acquisition period was impaired in the animals given 1 and 2 mg/g of neonatal MSG. Their retention scores were also impaired in comparison with the control animal. The behavioral impairment recovered with pre-treatment with GDEE. No significant changes were observed in the concentrations of transmitter substances, including amino acids and monoamines. These results suggest that neonatal MSG destroys the hippocampus and impairs acquisition and retention of discrimination learning through the mechanism of glutamate receptors. PMID- 8358623 TI - Alterations of corticotropin-releasing factor-like immunoreactivity in different brain regions after acute cocaine administration in rats. AB - Corticotropin-releasing factor (CRF) may mediate some of the neuroendocrine and behavioral responses to cocaine. In this study, the distribution of CRF-like immunoreactivity (CRF-LI) was determined in the hypothalamus and in several extrahypothalamic brain regions after acute cocaine administration in handled rats. CRF-LI decreased dose-dependently with cocaine administration in the hypothalamus and in the basal-forebrain structures. A small dose of cocaine (7.5 mg/kg) decreased CRF-LI in the hippocampus and in the frontal cortex. A significant, selective, dose-dependent increase in CRF-LI was found in the amygdala after cocaine injection. None of the investigated doses of cocaine altered CRF-LI in the striatum. These results suggest that acute cocaine administration alters brain CRF systems to contribute behavioral and neuroendocrine responses to cocaine. PMID- 8358625 TI - Simultaneous demonstration of Fos-like immunoreactivity and 2-deoxy-glucose uptake in the inferior colliculus of the mouse. AB - Fos-like immunoreactivity and 2-deoxy-glucose uptake can be visualized in adjacent sections of the same brain by applying a modified cytochemical reaction protocol. This study demonstrates that the two methods correspond to each other in mapping the tonotopic organization of the inferior colliculus. PMID- 8358624 TI - A68 is a component of paired helical filaments of Gerstmann-Straussler-Scheinker disease, Indiana kindred. AB - Gerstmann-Straussler-Scheinker disease in the Indiana kindred is pathologically characterized by prion protein amyloid deposits and neurofibrillary tangles (NFT) with paired helical filaments (PHF). Using antibodies to various domains of the tau molecule, we investigated the composition of PHF in this family by immunocytochemistry and immunoblot analysis. The results indicate that A68 is a component of NFT in this family as it is in Alzheimer's disease, and suggest that post-translational modifications of tau leading to formation of A68 are not unique to Alzheimer's disease. PMID- 8358626 TI - Immunocytochemical identification of photoreceptor populations in the tree shrew retina. AB - The presence and retinal distributions of short-wavelength-sensitive cones, long wavelength-sensitive cones, and rods were assessed in the retina of the tree shrew Tupaia belangeri using visual pigment antibodies OS-2, COS-1 and anti rhodopsin, respectively. Results demonstrated a clear immunocytochemical differentiation of the three photoreceptor types with each showing regional variation in density across the retina. PMID- 8358627 TI - A geometrical description of horizontal cell networks in the turtle retina. AB - Networks of physiologically identified H2 horizontal cells in the turtle retina were labeled by intracellular injection of Neurobiotin. We obtained a quantitative description of the neighbourhood relations in the dye-coupled cell mosaics by using the somata as centers for the Voronoi-Delaunay construction. Computational models simulating the experimental data are presented. PMID- 8358628 TI - The variation in safety factor with myelinated axon diameter: experiments with low sodium perfusion. AB - Theoretical considerations suggest that myelinated axons of a small diameter (and therefore with a low conduction velocity) also have a low safety factor. That these axons, many of which are involved in the mediation of pain, may fail first when action potential conduction is inhibited may explain the analgesic properties of local anesthetics. We have tested this hypothesis by perfusing frog myelinated axons with a low concentration of sodium ions and monitoring the reduction in conduction velocity, and the tendency to conduction failure. It was found that axons conducting action potentials at below 10 m/s are affected to the greatest extent by low sodium perfusion, indicating that slow conducting axons do have a low safety factor and confirming the earlier theoretical prediction. PMID- 8358630 TI - Responses of rat striatal neurons during performance of a lever-release version of the conditioned avoidance response task. AB - Neural activity was recorded from 218 sites in the striatum (caudate-putamen and nucleus accumbens) of rats trained on a lever-release version of the conditioned avoidance response (CAR) task, in which an auditory signal elicits a short latency, forelimb withdrawal. > 80% of these recording sites showed task-related activity, including neurons that responded to the auditory stimulus (signal related cells), the lever-release (response-related cells), or both of these events (signal/response-related cells). Histological analysis revealed a predominance of signal-related neurons in medial striatum, whereas lateral recording sites mainly showed response-related activity. Haloperidol (0.1 mg/kg s.c.), a widely used neuroleptic that impairs CAR performance, significantly attenuated task-related neural activity without altering the latency of the neural response or spontaneous firing rate. Collectively, these results, which demonstrate the usefulness of the lever-release CAR paradigm for assessing striatal function, suggest that the sensory and motor aspects of the CAR task are processed by different striatal regions. Moreover, haloperidol appears to disrupt the striatal processing of both sensory and motor information. PMID- 8358629 TI - Serotonin 5-HT3 receptors in schizophrenia: a postmortem study of the amygdala. AB - Alterations in density of some serotonin receptor sites (5-HT1A receptors, 5-HT2 receptors and 5-HT uptake sites) have been reported in postmortem studies of brain obtained from subjects with schizophrenia, suggesting a disturbance in serotonergic transmission in schizophrenia. The purpose of the present study is to investigate [3H]-LY278584 binding to serotonin 5-HT3 receptors in postmortem samples of amygdala from schizophrenic and matched control subjects. As all of the schizophrenic patients but none of the controls had been treated with neuroleptics, we first investigated in rodents the effects of short-term and long term haloperidol administration on limbic 5-HT3 receptors, and we found no effects. No differences in the maximum number of 5-HT3 binding sites (Bmax) or equilibrium dissociation constant (Kd) between schizophrenics and controls were found in amygdala. This study does not support the presence of an alteration of 5 HT3 receptors in amygdala in schizophrenic patients. PMID- 8358631 TI - Blockade of morphine-induced analgesia and tolerance in mice by MK-801. AB - The effect of MK-801 on morphine-induced analgesia, tolerance and opioid binding sites was examined in mice. In analgesia studies, mice received either naloxone or MK-801. Controls were injected with saline. Mice were then injected with morphine 10 or 30 min following naloxone or MK-801, respectively, and tested for analgesia (tail flick assay) 45 min later. Pretreatment with naloxone or MK-801 blocked morphine-induced analgesia. In tolerance studies, mice were pretreated with either saline or MK-801. Thirty minutes later, mice were injected with either saline or morphine (acutely or chronically) and tested for analgesia 24 h later. Pretreatment with MK-801 partially or completely blocked the development of acute and chronic tolerance, respectively. In binding studies, MK-801 displaced [3H]naloxone poorly compared to naloxone or morphine. Together, these data suggest a role for NMDA receptors in morphine-induced analgesia and tolerance. The poor inhibition of the [3H]naloxone binding sites by MK-801 supports the possibility that MK-801 might not act directly on the opioid receptors, but rather, inhibits morphine-induced analgesia and tolerance by some other mechanisms. PMID- 8358634 TI - Ultrastructural changes of osteoclasts on hen medullary bone during the egg laying cycle. AB - 1. The ultrastructure of osteoclasts on hen medullary bone during the egg-laying cycle was observed by electron microscopy. 2. At 0 to 6 h after oviposition, osteoclasts lacking ruffled borders were attached to the bone via the clear zone and appeared to have ceased bone resorption. Small vacuoles were scattered throughout this cytoplasm. 3. At 9 to 21 h after oviposition, most of the osteoclasts had ruffled borders and appeared to be resorbing bone. The ruffled borders at 15 h were well developed, whereas at 9, 18 and 21 h they were poorly developed or showed similarities in structure to the clear zone. The small vacuoles were concentrated under the ruffled borders at 9 h and then decreased. 4. These results demonstrate cyclic changes in osteoclasts during the egg-laying cycle, indicate that ruffled borders form at the beginning of bone resorption and suggest that they are derived from the clear zone and the small vacuoles. The results also indicate that the ruffled borders fuse into the clear zone and disappear at the completion of bone resorption. PMID- 8358633 TI - Incidence and classification of early embryonic mortality in broiler breeder chickens. AB - 1. Unusually high early embryonic mortality (EEM) was observed in hatching eggs from broiler compared with white or brown table-egg breeders in Atlantic Canada. Broiler breeder EEM in Atlantic Canada was twice the EEM in broiler breeders from other areas of North America. 2. Comparisons of holding temperatures (18 and 30 degrees C) for 24 h after egg collection, in combination with a storage time of 0 or 7 d at 18 degrees C prior to incubation, were made using the criteria: embryo development (stage), and size at 0, 3, 6 and 9 d incubation, EEM, late embryonic mortality (LEM) and hatchability (HAT). 3. Stage of development of embryos, at 0 d incubation, was highest for eggs held for 24 h at 30 degrees C and stored for 7 d. Embryo stage, weight and length at 3, 6 and 9 d incubation were positively correlated. 4. Hatchability of fertile eggs was lowest (66.5%) for eggs held for 24 h at 30 degrees C and stored for 7 d and highest (87.2%) for eggs held for 24 h at 18 degrees C and stored for 0 d. Holding temperature and storage time significantly influenced EEM and LEM. 5. EEM classification differed for strain of breeder. In broiler breeders the majority of the EEM was at a relatively late stage of development (exhibiting an obvious blood ring with a visible embryo). In comparison, EEM from table egg breeders was distributed equally among three categories. PMID- 8358632 TI - Identification of a 34 kDa protein specific to synaptic vesicles. AB - In this study, we used synaptic vesicles purified from the electric organ of marine electric rays to search for novel molecules which have important functions in synaptic transmission. Proteins that copurified with synaptic vesicles were used to immunize rats, and the resulting antisera were then used to further characterize the vesicle proteins. One of the antisera recognizes a protein of 34 kDa, p34, that has several characteristics which suggest it is a synaptic vesicle specific protein: (1) it copurifies exclusively with the synaptic vesicle peak during permeation chromatography on a controlled pore glass beads column, (2) it can be immunoprecipitated with intact synaptic vesicles and (3) it is specifically localized to the nervous system. The results suggest that p34 is a synaptic vesicle specific protein with a widespread distribution in the nervous system. PMID- 8358635 TI - Effects of the sex-linked dwarf gene (dw) on skeletal muscle cellularity in broiler chickens. AB - 1. The number and size of muscle fibres and the DNA concentration in m. pectoralis superficialis of normal (Dw+/-) and dwarf (dw/-) White Plymouth Rock females were investigated at the ages of 9 and 52 weeks. 2. Live weight and total meat was reduced by 37.4 and 42.8% in dw/- as compared with Dw+/- females at the age of 9 weeks. The suppressive effect of the dwarf allele on the weight of m. pectoralis superficialis was 40.6% (67.8 v. 40.3 g in Dw+/- and dw/- genotypes). This reduction in weight was accompanied by a similar decrease of DNA content (28.8 v. 17.1 mg, i.e. 40.6%), a decrease in number of muscle fibres (829 x 10(3) v. 654 x 10(3), i.e. 21.2%) and fibre diameter (30.80 v. 28.95 microns, i.e. 6.0%). In mature hens, the differences between genotypes Dw+/- and dw/- were slightly smaller. 3. The different relationships between the muscle growth traits studied are discussed. PMID- 8358636 TI - The relationship between yolk cholesterol and total lipid concentration throughout the first year of egg production in the domestic fowl. AB - 1. Variation of egg yolk cholesterol and total lipid concentration (mg/g wet yolk) throughout the first year of egg production for the domestic fowl is described. 2. Yolk cholesterol concentration decreases between 20 and 30 weeks of age, and then remains constant until 70 weeks of age. Yolk total lipid concentration increases to a maximum at 40 weeks of age before decreasing to its original value at 60 and 70 weeks of age. 3. Bird means for yolk cholesterol and total lipid concentration are negatively related at 20 weeks of age, and essentially independent for the remainder of the first year of egg production. 4. Variation for yolk cholesterol concentration between 30 and 70 weeks of age appears to be a consequence of differences in the proportion of cholesterol to other lipid components. 5. Uptake of plasma lipoproteins characteristic of the immature bird is likely to be responsible for the high yolk cholesterol concentration at 20 weeks of age. PMID- 8358637 TI - Microbiological survey of five poultry processing plants in the UK. AB - 1. Neck skin samples were taken from chickens and turkeys at all the main stages of processing to monitor changes in total viable count (TVC) and counts of coliforms and pseudomonads. 2. Processing reduced TVC by up to 100-fold. Geometric mean counts after packaging were log10 4.4 to 5.3 CFU/g whilst corresponding counts of coliforms were 2.7 to 3.8 CFU/g. 3. Increases in mean TVC or coliforms as a result of either defeathering or evisceration did not exceed 0.6 log. 4. Pseudomonads represented only a minor fraction of the initial microflora of the bird and were often reduced by scalding to a figure which could not be detected by direct plating of samples; however, subsequent contamination resulted in means between log10 2.9 and 4.0 CFU/g for packaged carcases. 5. Although Staphylococcus aureus was readily isolated from defeathering equipment, mean counts from defeathered carcases were always below log10 3.0 CFU/g. PMID- 8358638 TI - Toxicity of raw limabeans (Phaseolus lunatus L.) and limabean fractions for growing chicks. AB - 1. In a 4-week feeding trial, raw limabeans Phaseolus lunatus and extracted limabean fractions were tested as dietary ingredients in broiler starter diets. During the study, parameters such as body weight, lengths of intestinal sections as well as weights and histopathology of some organs (liver, kidney, heart, adrenals, spleen, brain, pancreas and small intestine) were investigated. 2. With the exception of broiler chicks fed on the diet containing soaked/boiled limabeans, growth was severely hindered in chicks fed on diets containing raw limabeans and limabean fractions. 3. Significant treatment differences in lengths of some intestinal sections were observed. The relative weights of the liver and spleen decreased, and the weights of the kidney, adrenals, small intestine and caecum increased in birds fed on diets containing raw limabeans and fractions containing high concentrations of anti-nutritional factors, whereas there was no difference in the weights of these organs in soaked/boiled limabean diet-fed birds. 4. The inclusion of raw limabeans, base-soluble protein, acid-soluble protein, defatted limabean and ether extracted meal in the diets for growing chickens was shown to produce serious histopathological changes within the livers, kidneys, pancreases, spleen and lungs. PMID- 8358639 TI - Comparative growth and development of the digestive organs and of some enzymes in broiler and egg type chicks after hatching. AB - 1. Body weight, the weight of digestive organs and activities of some digestive enzymes were determined from hatching to 14 d of age in meat- and egg-type chickens. 2. Relative daily food intake and growth rate were much higher in meat- than in egg-type chickens. Relative daily food intake peaked at 30% of body weight at 3 d of age in meat-type, and at 20% of body weight at 6 d of age in egg type chickens and then decreased gradually. The corresponding values for growth rate were 20 and 14%. 3. Allometric growth of the small intestine, intestinal contents and liver was greater in meat-type chickens, but the growth of the pancreas attained a higher value in the egg-type birds. Diminution of the vitelline residue was similar in the two breeds. 4. Pancreatic digestive enzyme activities were similar between stocks, but activities in the small intestinal contents were lower in meat-type chickens. 5. The secretion of digestive enzymes in the newly-hatched meat-type chicken could be a limiting factor in digestion and, consequently, in food intake and growth. PMID- 8358640 TI - Precocious puberty in tamoxifen-treated cockerels: hypothalamic gonadotrophin releasing hormone-I and plasma luteinising hormone, prolactin, growth hormone and testosterone. AB - 1. The administration of the anti-oestrogen, tamoxifen (TAM) to juvenile chicks results in precocious puberty. In the present study the effects of TAM administration (1 mg/kg body weight on alternate days from 12 d of age) on testicular function, hypothalamic chicken gonadotropin-releasing hormone (cGn-RH I), plasma luteinising hormone (LH), growth hormone (GH), prolactin (PRL) and testosterone were studied in juvenile White Leghorn cockerels. 2. The increase in hypothalamic GnRH-I content which occurs during sexual development was advanced in TAM-treated birds, in association with precocious testicular development, an early rise of plasma testosterone content and enhanced comb growth. 3. Plasma LH concentrations behaved similarly and were higher in the TAM-treated than in control birds, during most of the experimental period. Plasma PRL concentration, which is high at hatching, decreased more quickly in TAM-treated than in control birds; plasma GH values were not consistently affected by TAM treatment. 4. Both the growth and the involution of the bursa of Fabricius in the TAM-treated cockerels preceded that in the control chicks. 5. It is concluded that TAM treatment induces precocious puberty in the cockerel by blocking the negative feedback action of aromatised testicular androgens on the hypothalamus. PMID- 8358641 TI - Effect of acute heat exposure on triglyceride transfer to the preovulatory follicles of the laying fowl (Gallus domesticus). AB - 1. The effect of acute heat exposure on triglyceride (TG) transfer to preovulatory follicles was studied in the laying fowl. 2. Heat exposure of laying fowl resulted in a 1.1 degree C rise in body temperature, a 10-fold increase in respiration frequency and mild hypocapnia and hypoxaemia. 3. Plasma and follicular tissue TG concentrations were not significantly affected by heat exposure, but plasma TG specific radioactivity decreased significantly and was negatively correlated with body temperature. 4. The transfer rate of TG to the preovulatory follicles was not affected significantly by hyperthermia. 5. We conclude that nutrient supply to the developing follicles is not compromised in acutely heat-exposed laying fowl. PMID- 8358642 TI - Susceptibility of two commercial single comb White Leghorn strains to calcium induced urolithiasis: efficacy of dietary supplementation with DL-methionine and ammonium sulphate. AB - 1. Susceptibility to calcium-induced urolithiasis was assessed in pullets of two commercial SCWL strains (A and B) reared together from 5 to 18 weeks of age on diets containing 10 g/kg calcium (normal calcium: NC) or 35 g/kg calcium (high calcium: HC). 2. Kidney damage was not observed in pullets reared on NC diets. For pullets fed on HC diets, strain A developed significantly greater kidney asymmetry, a higher incidence of gross kidney damage and a higher incidence of uroliths than strain B. 3. Supplementing the HC diet with 6 g/kg DL-methionine significantly reduced the incidence of calcium-induced gross kidney damage and urolith formation in both strains. Ammonium sulphate (5.3 g/kg) was significantly more effective than DL-methionine in reducing calcium-induced kidney damage. 4. Neither DL-methionine nor ammonium sulphate caused a measurable metabolic acidosis. Neither supplement consistently affected water consumption or manure moisture. PMID- 8358643 TI - Defective Down syndrome in chicks is not caused by riboflavin deficiency in breeders. AB - 1. Riboflavin-deficient practical and semi-purified diets were fed to broiler breeder hens. 2. Yolk and albumen riboflavin concentrations were depressed by the deficient diets and cases of curled toes were seen in the chicks. 3. The few instances of defective down did not resemble cases seen in field outbreaks of a condition involving depressed hatchability and a defective down syndrome. 4. It is concluded from observations in this experiment and in the field outbreaks that there is a condition in breeding chickens causing depressed hatchability and defective down that is not attributable to riboflavin deficiency. PMID- 8358644 TI - Application of epidemiologic principles and methods to investigating and controlling equine infectious diseases. AB - Epidemiology is a tool much like any other diagnostic tool that the practitioner uses as an aid in the complete physical examination of the group of animals. It can be used to generate a specific differential diagnosis list. Epidemiology is especially useful to design a disease control and prevention program by helping to elucidate the key determinants of disease occurrence. PMID- 8358645 TI - Equine influenza. AB - Influenza continues to be one of the most important diseases of horses despite the availability and widespread use of equine influenza vaccines for almost 30 years. In recent years, infection with the influenza A/equine/2 subtype has become endemic in the equine populations of North America, Europe, and Scandinavia. Continued antigenic drift of field virus has compromised the efficacy of vaccines, most of which contain antigens prepared from influenza viruses isolated more than 10 years ago. This article reviews the history, virology, epidemiology, pathogenesis, immunology, clinical presentation, diagnosis, treatment, control, and prevention of influenza in horses and emphasizes recent developments in diagnostic methods and vaccine technology. PMID- 8358646 TI - Rotaviral diarrhea. AB - Rotavirus poses a challenge each foaling season to farm managers and veterinarians in intensive horse breeding areas throughout the world. By understanding the epidemiology of the disease as well as characteristics of the virus, veterinarians can make sound recommendations on prevention and control of outbreaks. Even when effective prophylactic products are developed, farm management practices, including quarantine, disinfection, and hygiene, will always need to be in force to prevent any contagious disease outbreak. PMID- 8358647 TI - Equine rabies. AB - With the continued increase in the number of wildlife rabies cases reported across the United States and Canada, this disease will remain a threat to the horse as the potential for exposure to infected wildlife and other domestic animals is likely to also increase. Because there are no rapid, definitive antemortem diagnostic tests, the tentative diagnosis is based upon the variable and sometimes nonspecific clinical signs. Although the CSF analysis may be helpful in some cases, it may not be abnormal. Nor is collection of the specimen always practical in the field situation. The FAT on neural tissue remains the most accurate diagnostic test; therefore, the diagnosis of rabies can be definitively made only at necropsy. Vaccination of horses with the inactivated rabies vaccines is thought to be safe and effective and may be advised for horses in endemic areas. Practitioners should consult with state or provincial authorities regarding the need for vaccination in their area. Veterinary technicians, veterinarians, and other animal health workers should be vaccinated against rabies. PMID- 8358648 TI - African horse sickness. AB - AHS is a noncontagious vector-borne disease of Equidae caused by Orbiviruses. Species susceptibility in decreasing order is horses, mules, donkeys, and zebras. The main vectors of AHS are culicoides. The disease is endemic in sub-Saharan Africa, but epizootics have occurred outside of this area on several occasions. The most recent outbreaks outside of the endemic area were in Spain, Morocco, and Portugal between 1987 and 1990. AHS causes mortality up to 95% and is classically divided into four clinical forms: the pulmonary, cardiac, mixed, and horse fever forms. Pathologic changes are subcutaneous and intermuscular edema and lung edema. The most consistent clinical signs include fever, nonpurulent conjunctivitis, and increased respiratory rate. Prevention and control measures include quarantines, control of insects, and vaccination. There is no treatment for AHS. Neurotropic strains of AHSV may cause retinitis and encephalitis in humans. PMID- 8358649 TI - Strangles. AB - The etiology, epizootiology, pathogenesis, and clinical presentation of strangles are described. Streptococcus equi, the causative organism, is highly host-adapted to Equidae and shows no antigenic variation. Protective immunity apparently is mediated by a combination of serum opsonic and nasopharyngeal mucosal humoral responses. Vaccines based on M protein or inactivated bacterial suspensions may reduce the clinical attack rate by 50%, a level of protection much lower than that produced during recovery from strangles. PMID- 8358650 TI - Rhodococcus equi. AB - This article summarizes recent advances in understanding of the epidemiology, pathogenesis, clinical and laboratory diagnosis, immunology, treatment, and control of Rhodococcus equi infections in foals. Our understanding of these aspects currently is sufficient to ensure control of this problem on affected farms and in infected foals. More information, however, is needed on factors predisposing foals to R. equi pneumonia, in particular, the nature of the naturally occurring cellular immunodeficiency in foals of 2 to 4 months of age, which also predisposes them to severe respiratory infection with certain other intracellular pathogens. In addition, the relative importance of R. equi pneumonia in the context of other causes of lower respiratory tract infection of foals needs to be defined. PMID- 8358651 TI - Salmonellosis. AB - Salmonellosis is the most common infectious cause of diarrhea or colitis in horses. It can be associated with high fatality rates in patients with compromised host defenses. The increasing incidence of infection and antimicrobial resistance present a challenge for the practicing veterinarians. The epidemiology and pathogenesis of salmonellosis are reviewed. Diagnosis, treatment, and control of disease are discussed. PMID- 8358652 TI - Potomac horse fever. AB - E. risticii, the cause of classic Potomac horse fever, is now known to produce two disease syndromes: EEC and EEA. The pathogen appears to commonly infect horses based on seroepidemiologic studies; however, the method of transmission remains unknown. The most common clinical disease is EEC, commonly called Potomac horse fever, which presents a wide spectrum of clinical signs. Diagnosis is currently dependent on serology, which frequently does not lead to a definitive diagnosis and at best results in a retrospective diagnosis. A new diagnostic approach, polymerase chain reaction, may offer a rapid and accurate diagnostic test but is yet to be proven. Antimicrobials found to be highly effective in treating EEC include intravenous oxytetracycline and the oral combination of erythromycin and rifampin. Without an understanding of the mode of transmission, prevention of EEC will remain impossible. Although two commercial bacterins are available, vaccination does not result in complete protection. EEA is a recently recognized clinical syndrome caused by E. risticii. After recovery from EEC, pregnant mares may abort. Based on histologic examination, the aborted fetus appears to be a victim of an ehrlichial colitis as well as placentitis. The effect of antimicrobials and vaccination on the occurrence of EEA has yet to be investigated. PMID- 8358653 TI - Clostridia-associated enterocolitis in adult horses and foals. AB - A review of the literature describing clostridia-associated enterocolitis is presented. The bacteria, their toxins, and possible factors that interact to contribute to the pathogenesis of enterocolitis are described. Clinical signs associated with clostridia-associated enterocolitis, methods of diagnosis, treatments, and preventive strategies are discussed. PMID- 8358654 TI - Equine ehrlichiosis. AB - Equine ehrlichiosis is a seasonal disease of horses first reported in 1969. Clinical signs in horses include high fever, depression, partial hypophagia, anorexia, limb edema, petechiation, icterus, ataxia, and reluctance to move. Hematologic changes include leukopenia, thrombocytopenia, icterus, anemia, and inclusion bodies, principally in neutrophils and occasionally in eosinophils. Diagnosis is made by clinical signs and observing characteristic morulae in a blood smear with standard Wright's stain. Mortality is low unless secondary infection develops or injury occurs as a result of incoordination. Treatment with tetracycline produces prompt defervescence of fever and gradual improvement of clinical signs. PMID- 8358655 TI - Lyme disease (Lyme borreliosis) in horses. AB - This article reviews epizootiology, public health considerations, antibody testing, and molecular biology of Lyme borreliosis. Correlation of clinical signs with titer response is discussed. PMID- 8358656 TI - Leptospirosis. AB - Equine clinical leptospirosis has been primarily related to uveitis and the often recurrent sequelae of ocular changes. Reports of equine hepatic and renal involvement are sporadic. More recently, serovar bratislava has been identified as a host-adapted serovar in the horse. More significantly, reports of equine abortion and stillbirth have become more frequent in the literature. This is more than likely a result of improved diagnostic techniques, not of increased prevalence of disease. In addition to abortion, equine neonatal disease is becoming more frequently recognized in association with leptospira infection. Whether leptospiral infection results in abortion or diseased foals may depend upon the stage of gestation when the mare is exposed and host immune status. Antibiotic of choice for treatment of equine leptospirosis remains speculative, as specific equine studies have not been performed. Extrapolation from other species suggests that the use of streptomycin remains a good choice of therapy for the chronic shedding state and may be used in combination with other antimicrobials for treatment of acute disease. Penicillin or potentiated penicillins and tetracycline at appropriate to high end dosages are logical choices for the treatment of acute leptospirosis. PMID- 8358657 TI - The nursing practice corner. PMID- 8358659 TI - I offer the public the fruit of my pains. PMID- 8358658 TI - On-the-job exposure to HIV: reducing RNs' risk (continuing education credit). PMID- 8358660 TI - Lack of risk of HIV transmission. PMID- 8358661 TI - The do's and don'ts of marketing. AB - Marketing is a tough area for most dentists. They either reject it altogether (an attitude that is bound to go the way of the dinosaurs because of sheer economics) or they accept its role in principal but aren't sure about the choreography for the marketing moves. What's important for dentists who embrace marketing is that their actions are well thought out, planned and executed. Because the fallout from inappropriate or ineffectual marketing can be bottomless. The idea (a variation of that old adage) is to please most of the people most of the time, as in the cited rose example above. (Yes, Abby sided with the wife.) PMID- 8358662 TI - Meeting the needs of women in dentistry. PMID- 8358663 TI - Access and isolation problem solving in endodontics: anterior teeth. AB - Through a pictorial presentation of case studies, this paper examines the versatility of alternative methods of retention as a means of improving the overall access to the endodontically-involved tooth. Successful endodontics is the result of precise biomechanical instrumentation involving procedural manipulations that depend on a complete and unobstructed approach to the working field. This pictorial essay is aimed principally at clinicians who would ordinarily reject rubber dam isolation in those cases where the clinical pretreatment conditions are anything but ideal. PMID- 8358664 TI - Prosol-chlorhexidine irrigation reduces the incidence of bacteremia during ultrasonic scaling with the Cavi-Med: a pilot investigation. AB - The purpose of this pilot investigation was to determine whether the incidence of bacteremia following subgingival ultrasonic scaling and root planing could be reduced by the use, pre- and intraoperatively, of an irrigant containing 0.12 per cent chlorhexidine (CHX); Prosol. Individuals having evidence of significant periodontal disease (minimum of seven sites per quadrant 4.0 mm and bleeding on probing) were entered into this study. By use of a random number table, patients were assigned to either the experimental or control groups. The procedures, as described below, were carried out in a double blind fashion so that neither the investigator nor the patient was aware of whether Prosol or placebo was being used. The placebo solution was flavored to make it indistinguishable from Prosol. Patients were first anesthetized. Their gingival crevices were then irrigated using the Cavi-Med ultrasonic scaler. At this point, the ultrasonic action was not activated. Ten minutes later, ultrasonic scaling and root planing with the Cavi-Med unit were begun with a continuous flow of either the placebo or control solutions. Blood samples were taken preoperatively, while postoperative samples were taken one minute after completing the scaling of each quadrant and then 10 minutes after scaling the second quadrant. Routine aerobic and anaerobic bacterial culture methods were used to identify viable blood-borne bacteria. The results show that there was no difference in the distribution or presentation of periodontal disease between the experimental and control quadrants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358665 TI - [Mouth diseases in a prehistoric agricultural population of northeastern North America]. AB - There is no longer any question that the consumption of refined sugar is a factor in the development of dental caries. In fact, researchers now believe that the production of refined sugar and, particularly, its great availability and use in post-industrial populations has led to a virtual revolution in both the food industry and buccopathology. Clinical and epidemiological studies on the relationship between caries and sugar consumption have been conducted for more than 40 years, and the harmful effects of sugar consumption on the development of dental caries are now well known. Some authors have also demonstrated a historical relationship between caries and sugar over the last three centuries. Another food revolution that had an equally great impact on oral health occurred with the introduction of agriculture. This innovation is discussed from both a technical and food perspective. Agriculture modified the diet of ancient populations by providing new foods that were rich in carbohydrates and by introducing new cooking methods (food was now often boiled instead of being roasted). These two factors alone contributed to an increased rate of dental caries, but at the same time reduced the abrasion of occlusal surfaces and dental crowns. This paper documents the relationship between dental caries, occlusal abrasion, fractures and periodontal disorders, as well as the agriculture practises of an Amerindian population that lived between 1000 and 1500 A.D. in parts of what are now New York State, Quebec and Ontario. The author's findings confirm those of many other researchers who have investigated agricultural populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358666 TI - The questionable relationship between HIV and AIDS. PMID- 8358667 TI - Computerized occlusal analysis. PMID- 8358668 TI - A two-part energy burden imposed by growth of Enterobacter cloacae and Escherichia coli in sodium dodecyl sulfate. AB - Enterobacter cloacae, like most enteric bacteria, can grow in the presence of 10% sodium dodecyl sulfate (SDS). The bacteria tolerate the detergent and do not metabolize it. In a defined glucose-salts medium the growth rate remained unchanged (G = 55 min) as the detergent concentration was increased from 0 to 10% SDS. However, growth in SDS exhibited a two-part energy dependence. In part 1, the SDS-grown cells underwent rapid lysis when they ran out of energy. Cells that had entered stationary phase owing to carbon limitation lysed, while those that had entered owing to nitrogen or phosphorus limitation did not. We attribute part 1 of the energy dependence to SDS as a detergent. In part 2, the cells grown in 5 or 10% SDS exhibited longer lag periods, potassium accumulation, decreased cell yields, and higher oxygen consumption. The higher oxygen consumption occurred during both exponential phase and nitrogen-limited stationary phase. However, the decreased cell yield and higher oxygen consumption of SDS-grown cells were mimicked by cells grown in equivalent concentrations of sucrose or polyethylene glycol. We attribute part 2 of the energy dependence to SDS as a solute. Finally, with regard to the as yet unidentified bacterial osmotic stress detector, we used the micelle-forming nature of SDS to conclude that the detector was responding to turgor pressure-water activity rather than to osmolarity itself. PMID- 8358669 TI - Biodegradation of cycloalkane carboxylic acids in oil sand tailings. AB - The biodegradation of both an n-alkane and several carboxylated cycloalkanes was examined within tailings produced by the extraction of bitumen from the Athabasca oil sands. The carboxylated cycloalkanes examined were structurally similar to naphthenic acids that have been associated with the acute toxicity of oil sand tailings. The biodegradation potential of naphthenic acids was estimated by determining the biodegradation of both the carboxylated cycloalkanes and hexadecane in oil sand tailings. Carboxylated cycloalkanes were biodegraded within oil sand tailings, although compounds with methyl substitutions on the cycloalkane ring were more resistant to microbial degradation. Microbial activity against hexadecane and certain carboxylated cycloalkanes was found to be nitrogen and phosphorus limited. PMID- 8358670 TI - Host range and transfer efficiency of incompatibility group HI plasmids. AB - HI plasmids are distinguished by their thermosensitive mode of conjugation (transfer efficiency is optimal at 22-30 degrees C) and their capacity to encode multiple antibiotic resistance. These traits have implicated HI plasmids as potential vectors in the dissemination of antibiotic resistance among pathogenic and indigenous bacterial species in water and soil environments. We compared the transfer efficiency of HI plasmids with that of plasmids from 13 other incompatibility groups at 37, 24, and 14 degrees C in intragenic conjugations between laboratory strains of Escherichia coli K-12 under in vitro conditions. Only the HI plasmids and a representative plasmid from incompatibility groups M, N, P alpha, T, and W were observed to be transmissible at 14 degrees C. These plasmids, along with HI plasmids and the related HII representative, were tested for their host range and transfer proficiency to Enterobacteria species and some other Gram-negative organisms of environmental significance at 24 and 14 degrees C. Notable differences in the host range of HI plasmids compared with plasmid representatives from the other enterobacterial groups were not evident at 24 degrees C. At 14 degrees C, R478 (HI2) displayed the broadest host range and transfer proficiency among the test plasmids. The ability of several plasmid groups, including HI, to transfer at 14-24 degrees C to Vibrio cholerae non 01, Salmonella typhi, and the fish pathogens Aeromonas salmonicida, Vibrio anguillarum, and Yersinia ruckeri needs to be corroborated by in situ studies. PMID- 8358671 TI - Factors affecting PCB degradation by an implanted bacterial strain in soil microcosms. AB - Pseudomonas testosteroni B-356 was able to degrade approximately 50% of the Aroclor 1242 mixture in shaken culture. The aims of the present study were to evaluate the capabilities of this bacterial strain to degrade PCBs in soil microcosms and to identify some of the factors likely to favor the degradative performance of the implanted bacteria. The presence of biphenyl as cosubstrate was the most important factor affecting PCB degradation in soil. However, because biphenyl was rapidly depleted in soil microcosms, repeated addition of small amounts of biphenyl to maintain a constant level of the cosubstrate allowed the achievement of a higher degree of degradation of the tetrachlorinated components of Aroclor 1242 than was achieved with a single addition at the time of inoculation. Degradation of di- and tri-chlorinated PCB congeners was less affected by repeated addition of biphenyl because these congeners were degraded very fast and complete degradation was achieved before biphenyl was depleted in the soil. Biodegradation was also related to bioavailability of the substrate. We observed that the proportion of each congener degraded was higher in the microcosms receiving both the producer of the surface-active agent, Alcaligenes faecalis B-556, and strain B-356. Under the best conditions (presence of a constant level of biphenyl and of strain B-556) P. testosteroni B-356 was able to degrade approximately 30% of the Aroclor 1242 added to soil microcosms; some other factors reducing the PCB degradation capabilities of the implanted bacteria are also discussed. PMID- 8358672 TI - Genetic mapping of bfmA mutation causing fatty acid deficiency in Bacillus subtilis. AB - Bacillus subtilis strain 626, defective in the bfmA gene, is a derivative derivatives of B. subtilis strain 168 and requires branched short-chain carboxylic acids for growth. Branched-chain 2-keto acid decarboxylase activity and fatty acid synthesis in B. subtilis strain 626 were 14 and 7%, respectively, of their levels in strain 626-2R, a spontaneously reverted strain. These results indicate that the bfmA mutation is in either the branched-chain 2-keto acid decarboxylase gene itself or its controlling gene. Thus, primer synthesis from the 2-keto acid substrate in strain 626 is defective, causing a deficiency in fatty acid synthesis. A bfmA mutation was transferred to a suitable genetic background and analysed. The bfmA strain, CAC1, was competent and motile, and required 50 microM CaCl2 or 5 microM FeCl3 for growth on glucose minimal agar plates. The bfmA gene was mapped between glyC (320 degrees) and ctrA (325 degrees) and estimated to be at 320 degrees by protoplast fusion and PBS1 phage transduction. PMID- 8358673 TI - Comparative study of the body surface electrocardiogram in double-muscled and conventional calves. AB - The purpose of this work was to study electrocardiographic features of double muscled beef cattle. Electrocardiograms were recorded on one to six occasions from each of a group of 18 conventional calves of the Friesian breed and 29 double-muscled calves of the Belgian White and Blue breed. Ages of the calves at the times of examination ranged from eight to 348 days. The Holmes semi orthogonal lead system was used. The waves and interval durations and the tridimensional P, QRS, and T modal vector orientation and amplitude were calculated. The magnitude of the cardiac vectors was significantly lower and the ventricular waves and QT interval duration significantly shorter in the double muscled than in the conventional calves. The P modal vector pointed significantly less downwards and the QRS modal vector pointed significantly more forwards and less up- and rightwards in the Belgian White and Blue, than in the Friesian group. Most of the observed differences might be a consequence of the bodily, and more specifically the thoracic, conformation of the former calves. However, the lower cardiac vector magnitude and shorter wave and interval durations might also reflect lower cardiac mass in the double-muscled subjects. PMID- 8358674 TI - Characterization of Escherichia coli isolated from cases of avian colibacillosis. AB - Forty-four western Canadian isolates of Escherichia coli associated with colibacillosis of turkeys and chickens were examined for serotype, antibiotic resistance, and production of aerobactin. The isolates belonged to fourteen O serogroups, with 39% of the strains being non-typeable. A high frequency of resistance to tetracycline, kanamycin, neomycin, cephalothin, streptomycin and erythromycin was observed. Most isolates produced aerobactin. Ten E. coli belonging to serogroups O1, O2 and O78 were also examined for pili production, hemagglutination, serum sensitivity, production of iron-regulated outer membrane proteins (IROMPS), and virulence. All isolates examined produced pili, exhibited mannose-sensitive hemagglutination of avian red blood cells and produced IROMPS under iron-restricted growth conditions. The five isolates of serogroup O1 and O2 were resistant to killing by turkey serum and were highly virulent. Only two of the five isolates of serogroup O78 were serum resistant. No correlation between serum resistance and virulence was observed in serogroup O78. PMID- 8358676 TI - Lack of effect of recombinant bovine interferon alpha I1 in the treatment of experimentally-induced bovine warts. AB - Fifteen four-month old calves were inoculated, on five scarified sites on each side of the neck, with a suspension of ground wart tissue from a steer naturally infected with bovine papilloma virus 1. Warts started to appear about one month postinfection and were measurable in ten calves two months postinfection, when the trial started. After stratification on the size of the warts, all fifteen calves were allocated randomly to one of the following treatment groups: twice weekly intramuscular injections of 5 mg recombinant bovine interferon alpha I1 (rBoIFN alpha I1), weekly injection of 5 mg of rBoIFN alpha I1 or placebo, for three weeks. The biggest wart on each calf at the beginning of the trial was measured and photographs of all warts were taken weekly for five weeks. An analysis of covariance on the log of the volumes of warts during the five weeks of the trial showed a significant difference between groups (p = 0.026). Warts in treated groups tended to grow faster than in the placebo group. PMID- 8358675 TI - The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) colorimetric assay for the quantitation of Actinobacillus pleuropneumoniae cytotoxin. AB - Using swine neutrophils as target cells, two MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium) colorimetric assay systems, one with and one without phorbol 12-myristate 13-acetate (PMA) stimulation were established for the quantitation of Actinobacillus pleuropneumoniae cytotoxin. The MTT assays were optimized for the number of neutrophils, incubation time, and PMA concentration by a series of experiments. The optimal conditions were 25 x 10(4) cells/well incubated for four hours for the assay system without PMA stimulation, and 12.5 x 10(4) cells/well incubated for two hours for the assay system with PMA stimulation. One culture supernatant of a toxigenic Pasteurella multocida strain and five A. pleuropneumoniae cytotoxin preparations produced from three A. pleuropneumoniae strains were used to test assay reproducibility. Results showed both assays were reproducible with a coefficient of variation ranging from 7.8 to 18% for the assay system without PMA stimulation and from 10.7 to 18.2% for the assay system with PMA stimulation. The PMA-stimulated assay had 40 to 60-fold higher sensitivity than the nonstimulated MTT assay. The MTT assay also was applied to the measurement of neutralizing antibody titers against A. pleuropneumoniae cytotoxin. PMID- 8358677 TI - The predictive value of pelvimetry in beef cattle. AB - To elucidate reasons for failure of pelvimetry to predict dystocia, we collected data from 1146 heifers and 210 cows in five beef cow herds in Saskatchewan. We assessed the reliability of pelvic area measurements, the generalizability of findings, various modifications of the technique, and the statistical association between pelvic area measurements and dystocia. The repeatability (kappa) of pelvic area measurements between and within veterinarians for the Rice and Krautmann pelvimeters were low to moderate, indicating pelvic area measurements were imprecise. The positive predictive values and sensitivities of pelvic area measurements were consistently poor across herds, years of study, breeds of heifers, times of measurement, various pelvic area cut-off points, and sires. Various modifications of the technique, including pelvic area/calf birth weight ratios, pelvic area/heifer weight ratios, and Ko's calving prediction equation were also poor on-farm tests for predicting dystocia. Although the mean pelvic area in heifers with dystocia was smaller than those without dystocia, there was a large overlap in the distribution of their measurements. Far too many heifers with a small pelvic area had no dystocia (false positives) and far too many heifers with a large pelvic area had dystocia (false negatives) for pelvimetry to be useful. We conclude there is little evidence to justify the continued use of pelvimetry as an on-farm test to reduce dystocia in beef cattle. PMID- 8358679 TI - Chlamydia psittaci infection and associated infertility in sheep. AB - Nineteen ewes were injected subcutaneously with the agent of enzootic ovine abortion, Chlamydia psittaci serovar 1, at 50 days gestation. Placental and fetal tissues were examined at 15 days postinfection and thereafter at ten day intervals. Placental infection was detected at 15 days postinfection. Only postinoculation sera collected from postinfected ewes contained antibodies reactive to C. psittaci. Five (26%) chlamydial infected ewes experienced inapparent fetal loss before day 105 of gestation. This finding is significant since C. psittaci infection in sheep is commonly associated with abortion and not infertility. PMID- 8358678 TI - Characterization of Salmonella enteritidis strains. AB - A study was conducted to characterize 318 Salmonella enteritidis strains that were mainly isolated from poultry and their environment in Canada. Biotype, phagetype (PT), plasmid profile (PP), hybridization with a plasmid-derived virulence sequence probe, antibiotic resistance, outer membrane proteins (OMPs), and lipopolysaccharide (LPS) profiles were determined. Relationships of these properties to one another, and their diagnostic and pathogenic significance were assessed. Biotyping indicated that failure to ferment rhamnose was sometimes useful as a marker for epidemiologically related strains. Phagetyping was the most effective method for subdividing S. enteritidis; it distinguished 12 PTs. Phagetype 13 was occasionally associated with septicemia and mortality in chickens. The strains belonged to 15 PPs. A 36 megadalton (MDa) plasmid was found in 97% of the strains. Only the 36 MDa plasmid hybridized with the probe. Seventeen percent of the strains were drug resistant; all strains were sensitive to ciprofloxacin. Thirty-five of 36 strains possessed the same OMP profile, and 36 of 41 strains contained smooth LPS. PMID- 8358680 TI - Actinobacillus pleuropneumoniae culture supernatants interfere with killing of Pasteurella multocida by swine pulmonary alveolar macrophages. AB - The effect of Actinobacillus pleuropneumoniae culture supernatant on swine pulmonary alveolar macrophage (PAM) functions was studied. The A. pleuropneumoniae culture supernatant was toxic to PAMs when tested by MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) release assays. Biological activity of the supernatant was ascribed to cytotoxins. Both the LDH and MTT assays were used for measurement of crude A. pleuropneumoniae cytotoxin concentration with good reproducibility. A preparation containing 6,800 toxic units/mL (determined by MTT assay) was used for subsequent experiments. The objective was to study the effect of crude cytotoxin on the ability of swine PAMs to kill Pasteurella multocida. Phagocytosis of opsonized P. multocida type A by PAMs was not efficient. Only 8% of incubated organisms were ingested by noncytotoxin-treated PAMs after 30 min phagocytosis. The bactericidal effect of noncytotoxin-treated PAMs only last for 60 min, after which, the rate of growth of surviving P. multocida exceeded the rate of bacterial killing by PAMs. Complete elimination of P. multocida by PAMs was not observed in this study. A total loss of ability to kill P. multocida by PAMs was seen when the PAMs were pretreated with a high concentration (340 toxic units/mL) of A. pleuropneumoniae cytotoxin. If the PAMs were pretreated with a low concentration (3.4 toxic units/mL) of cytotoxin, a significant reduction in the killing of P. multocida was still observed. The reductions in phagocytosis, phagosome-lysosome fusion (demonstrated using yeast particles of Candida albicans), and oxidative burst (demonstrated by nitro blue tetrazolium reduction (NBT) assay) may have contributed to the impaired killing of P. multocida by PAMs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358681 TI - Effects of Pasteurella haemolytica culture supernate on bovine tracheal smooth muscle. AB - Pasteurella haemolytica leukotoxin is a ruminant specific leukotoxin that has been implicated in the pathogenesis of shipping fever in cattle. The present study was undertaken to determine the effect of this toxin on bovine airway smooth muscle. In vitro, the addition of culture supernate containing leukotoxin to bovine tracheal smooth muscle resulted in contraction of 55% of the muscle strips tested. Maximum responses were reached rapidly during cumulative additions of this material. In 95% of the muscle strips that responded, maximum responses were obtained after the addition of one or two cumulative doses. Repeated additions of culture supernate resulted in decreased responsiveness. Since responsiveness to other agonists was not affected, these results suggest the development of a condition similar to tachyphylaxis. The contractions were inhibited by antihistamines. Diphenhydramine, at a concentration of 10(-6) M (dose-ratio 7), and mepyramine, at a concentration of 2 x 10(-7) M (dose-ratio 56), blocked the contractions by 84% and 100% respectively. In addition, the contractions were blocked by the muscarinic antagonist atropine, but this inhibition was much weaker (46%) and was present at high concentrations only. Inhibition of the contractions by H1 receptor antagonists suggests that the contractions are mediated via H1 receptors. Since the dose-response relationship is not typical of a drug-receptor interaction, it appears unlikely that the leukotoxin is a direct agonist of H1 receptors. It is proposed that an indirect mechanism of action involving the release of histamine by tissue mast cells is responsible for the leukotoxin-induced contractions. PMID- 8358683 TI - Influence of low dietary iron and iron overload on urethan-induced lung tumors in mice. AB - Weanling male CD-1 mice were fed low iron (7 ppm), control (120 ppm) and iron loaded diets (3000 or 5000 ppm) for 19 weeks. After seven weeks, the mice received 1.5 mg urethan/g ip, and tumor development was evaluated 12 weeks later. The low iron diet increased the incidence of lung adenomas by 86%. The iron loaded diets did not influence adenoma development. Tumor size was unaffected by iron status (p = 0.297). These results indicate that low iron body status promotes tumor development and are inconsistent with the hypothesis that excess iron promotes cancer growth and that low iron protects against tumor growth. PMID- 8358682 TI - Detection of Actinobacillus pleuropneumoniae in the porcine upper respiratory tract as a complement to serological tests. AB - Attempts were made to isolate Actinobacillus pleuropneumoniae from the nasal cavities and tonsils of 442 healthy pigs from 15 herds. Samples were streaked onto different media formulations. Serum samples were assayed for antibodies to A. pleuropneumoniae by enzyme-linked immunosorbent assay and complement fixation test. Actinobacillus pleuropneumoniae was isolated from the nasal cavities only in 24 pigs, from tonsils only in 90 pigs, and from both the nasal cavities and the tonsils in 11 pigs. A PPLO medium supplemented with lincomycin, bacitracin and crystal violet allowed recovery of A. pleuropneumoniae from more animals than a tryptic soy agar medium from both sites. Incubation of plates in an enriched CO2 atmosphere did not affect the recovery rate. Actinobacillus pleuropneumoniae belonging to serotypes 1, 2, 3, 5a, 5b, 7, 8, 10 and 12 were isolated, and, in several herds, more than one serotype were recovered. Serotypes of A. pleuropneumoniae were isolated from nine herds which were found seronegative to these. The isolation of A. pleuropneumoniae from the upper respiratory tract can be useful for detection of carrier pigs and complements serological screening. PMID- 8358684 TI - Response of heifer mammary gland macrophages and neutrophils to interferon-gamma stimulation in vitro. AB - The phagocytic and killing abilities of heifer mammary gland macrophages (M phi) and neutrophils were evaluated after exposure to recombinant bovine interferon gamma (rBoIFN-gamma) stimulation in vitro. Macrophages or neutrophils were cultured for 2 h with 0, 10(2), 10(4) and 10(5) units rBoIFN-gamma/mL. Phagocytosis assays were performed by incubation with Staphylococcus aureus at a leukocyte:bacteria ratio of 1:10. After 45 min, cells were stained with acridine orange and phagocytic and killing abilities were determined. Although rBoIFN gamma had no effect on M phi phagocytic activity, neutrophil phagocytic activity after incubation in 10(4) units rBoIFN-gamma (41.62%) was significantly higher than 0 (25.24%) or 10(2) units rBoIFN-gamma (24.73%). Neutrophil and M Phi killing abilities were not affected by any dose of rBoIFN-gamma. Results suggested that rBoIFN-gamma promoted neutrophil phagocytic activity, but did not affect neutrophil killing or overall M phi function in vitro. PMID- 8358685 TI - Injuries and public health in Canada. PMID- 8358686 TI - A pilot study of farm accidental injuries in Aberdeen, Saskatchewan. PMID- 8358687 TI - Home injuries to children. AB - To describe the circumstances around childhood injuries in the home, information on home injuries to children was collected in the emergency room of a pediatric trauma centre as part of an injury surveillance program. During a one-year period, data on 1,538 patients (age < or = 18 years) injured at home were recorded. An inverse s-shape association of home injuries with age was observed. Falls were the leading cause (51%); other children were struck by objects (18%) or sustained cutting/piercing injuries (9%). Age was positively associated with the likelihood of being struck by objects, cutting/piercing, and overexertion, but negatively associated with falls. Playing was the most common activity at time of injury. The peak time of injuries tended to be the early evening. Because most injuries occurred in an environment that seemed safe to parents, reduction in home injuries may require identification of potential hazards in the context of the stages of children's psychological and motor development. PMID- 8358688 TI - Childhood gunshot injuries in the Ottawa area. AB - To determine the incidence of non-fatal firearm injuries in the Ottawa area, we retrospectively reviewed the charts of all children admitted to the Children's Hospital of Eastern Ontario for firearm injuries in the last 15 years. The Children's Hospital is the only pediatric tertiary care care centre in the Eastern Ontario and Western Quebec areas, serving a child population of 600,000. Eighteen children were admitted to our hospital for firearm injuries during this period; six suffered long-term disabilities. The low number of non-fatal firearm injuries at our institution reflects national trends in the incidence of fatal firearm injuries in Canadian children and adolescents. PMID- 8358689 TI - Parental attitudes toward legislation for helmet use by child cyclists. AB - A random-digit dialing telephone survey was conducted in the second half of 1991 to examine parental attitudes toward legislation of helmet use by child cyclists. The surveyed population were 703 parents of at least one child aged 5-17 years who owned a bicycle and lived within Metropolitan Toronto. Five hundred sixty eight (80.8%) responding parents were in favour of the suggested legislation, 81 (11.5%) were against, and 54 (7.7%) had no opinion on the issue. The 95% confidence interval for the support rate was 78.9-83.7%. Although there was some variation in the level of support, at least two thirds of the respondents in every subgroup, except parents with teenaged children (aged 15-17 years), were in favour of the legislation. Legislation requiring bicycle helmet use by all children has strong support from the public. Additional surveys should be directed at public attitudes to legislation of helmet use by adults. PMID- 8358690 TI - [Profile of aged traffic victims on the road to Sherbrooke (Quebec)]. AB - This article draws a portrait of the victims, 65 years of age and over, of road accidents in a mid-size Quebec town. By examining four variables--age, sex, condition of the victims and the type of road users--we measured the magnitude and severity of road accident injuries in senior citizens, and identified those road users most at risk. Results indicate that, in the city of Sherbrooke as elsewhere in Quebec, road accident injuries are increasing slowly but constantly in this age group. Analysis of the severity of injuries and of the category of road users, shows that senior citizens have a high degree of vulnerability and are over-represented in statistics dealing with pedestrians who are victims of accidents. We discuss these results and their impact on public health. PMID- 8358691 TI - Cooperation and collaboration between a public health unit and midsized private industry in health promotion programming: the Polymer Heart Health Program experience. AB - In 1990, Cobequid Health Unit was approached by Polymer International, a plastics manufacturer, and planning began for a worksite cardiovascular risk factor screening and follow-up program. In 1991, 302 Polymer employees (89.1%) participated in a screening. Follow-up included smoking cessation programs, fitness opportunities, dietary counselling, and physician referral for further investigation of blood pressure and cholesterol levels. Policy and environmental changes include heart healthy foods at the cafeteria, development of non-smoking policy, and coverage under the corporate group insurance plan for dietary counselling. This process demonstrates the potential for public health and private industry to collaborate in preventive efforts and the principles required for success. PMID- 8358692 TI - Hypertension follow-up survey Laval, Quebec, 1988. AB - In 1988, a follow-up study of a group of hypertensives (n = 278), identified two years earlier in a prevalence survey (1986), was conducted. Blood pressure (BP) levels, treatment and control status and medical follow-up were assessed. Subjects were classified as either known hypertensives or newly identified hypertensives. There was a moderate increase in blood pressure control over the two-year period in known hypertensives. Approximately half of newly identified hypertensives remained untreated, uncontrolled; half became ex-hypertensives. One third of the ex-hypertensives, however, still had high-normal diastolic readings (85-89 mm Hg). Newly identified hypertensives reported less frequent medical visits and fewer non-pharmacological recommendations from their physicians than known hypertensives. The study suggests that follow-up and counselling on modifiable risk factors in borderline and mild hypertensives might not be up to recent Canadian and American guidelines. PMID- 8358694 TI - [Knowledge and attitude to sexually transmitted diseases and condoms in students and undergraduate students]. AB - Since sexually transmitted diseases (STDs) are a serious health problem among youth, proper understanding of knowledge about STDs, beliefs about condom use and associated factors are public health necessities. A self-administered questionnaire was sent to 2,920 randomly selected students and was returned by 59.3% of the sample. We observed a lack of knowledge in one third of students, negative beliefs on condom use for at least 20% of students and a low perceived risk to contract STDs. With multivariate analyses, we observed that male students, youths between 18-21 years of age and those who didn't have any sexual partner since their admission to the university should be the target of intervention programs. PMID- 8358693 TI - Calgary's needle exchange program: profile of injection drug users. AB - This report provides a baseline description of a sample of injection drug users who are clients of a needle exchange program in Calgary, Alberta. The results of the study suggest a relatively older, predominantly male clientele who reported heavy and sustained use of drugs, particularly cocaine. Despite a high level of awareness of the basic modes of HIV transmission, many respondents still engaged in high risk injection practices and/or sexual practices. In addition, self perception of risk was much lower than reported behaviour would indicate. Three percent of the sample were HIV+ at the time of the interview. In addition to providing a baseline for further evaluation, the results of this study can be used by program planners to target interventions more effectively. PMID- 8358695 TI - [Utilization of qualitative and quantitative methods to study the attitudes and beliefs related to AIDS in a Montreal population of Haitian origin]. AB - To determine attitudes and beliefs related to AIDS among the population of metropolitan Montreal of Haitian origin, we conducted serial cross-sectional surveys between 1987 and 1990 among a random sample of 777 men and women aged 15 to 39. Data on perceived risk of AIDS and attitudes towards HIV testing were collected in home settings using a combination of face-to-face structured interviews and a self-administered questionnaire. Multivariate analysis was conducted to determine predictors of attitudes towards people with HIV. The fear of being infected with HIV is great in this population. The social representation of illness in this community is very much influenced by religious beliefs. Scores for the five-item scale suggest only moderately favourable attitudes towards persons with HIV compared to Montrealers in general. Attitudes towards persons with AIDS were positively associated with years of schooling and a higher perceived risk of getting infected (p < or = 0.01). PMID- 8358696 TI - Concentrations of organochlorine pesticides in the adipose tissue of British Columbia residents. AB - Adipose tissue from a sample of 41 British Columbians was analyzed for a number of organochlorine pesticides. Pesticide concentrations were very low. Persistent fat-soluble compounds like DDT were found at the highest concentrations, whereas compounds that either quickly metabolize to other forms or are readily excreted were found at low levels or not detected. Data on age, sex, area of residence, occupation, diet and weight were obtained by interview. Increasing age was related to increasing levels of several of the persistent pesticides. Although there were insufficient data for statistical analysis, two individuals with potential occupational exposures had much higher levels of the pesticides than other subjects. Although population-based surveys of these organochlorine pesticides in human tissue may have little value, further study may be warranted for groups known to have had high exposures (e.g. occupationally exposed). PMID- 8358697 TI - Indicators for a sustainable society. AB - This study presents a set of 20 indicators that could be suitable for monitoring the progress of our society on the path to sustainable development. Based on the concept of a sustainable society, which explicitly links the four aspects of health, social equity, economy and environment, these indicators are meant for large administrative areas, and use mostly already available data. The approach is global and symbolic in order to be able to facilitate the integration of the four aspects in the public's mind. It is information for action that could be used in a systematic way for presentation to the general public and to decision makers, in the manner of everyday economic or weather indicators. PMID- 8358698 TI - The accuracy of ascertaining vital status in a historical cohort study of synthetic textiles workers using computerized record linkage to the Canadian Mortality Data Base. AB - Vital status of a cohort of 10,211 Quebec, synthetic textiles workers was ascertained through a probabilistic record linkage to the Canadian Mortality Data Base (CMDB); 5,033 of these workers were also traced using other sources. There was agreement in the vital status of all but 60 of the subjects traced jointly through the CMDB and the alternate sources. 41 subjects were declared 'deceased' from the CMDB but 'alive' from the alternate sources; it is likely that these subjects were indeed deceased. 19 subjects, declared 'deceased' with a fair degree of certainty from the alternate sources, were not identified from the computer search of the CMDB; 17 were found manually on the microfiche death records and two died outside of Canada. The probability of identifying deceased and living subjects from the CMDB was therefore estimated to be 98.2% (95% confidence interval: 97.5-98.7%) and about 100%, respectively. Estimates of cost are also presented, and it is concluded that use of the CMDB is the method of choice for tracing moderate to large cohorts. PMID- 8358699 TI - Leukemia and residential exposure to radon. PMID- 8358700 TI - Preconceptional folate and neural tube defects: time for rethinking. PMID- 8358701 TI - Children fathered by previous partners: a risk factor for violence against women. PMID- 8358702 TI - Concerning the link between tobacco smoking and impaired mental functioning. PMID- 8358703 TI - Q fever. AB - Q fever is an acute febrile illness first described in 1935 and now seen in many parts of the world. Human infection follows exposure to animals, especially domestic livestock. Recent outbreaks in metropolitan areas have implicated cats as the carrier of disease to humans. The etiologic agent, Coxiella burnetti, belongs to the family Rickettsiaceae, although it has distinct genetic characteristics and modes of transmission. Most recent attention has been focused on a number of large outbreaks of Q fever associated with medical research involving pregnant sheep. Although most infections are self-limited, some patients require prolonged treatment. Recent vaccines have had encouraging success in the prevention of disease in individuals at high risk of exposure. PMID- 8358704 TI - Delta hepatitis: molecular biology and clinical and epidemiological features. AB - Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection. PMID- 8358708 TI - Increased mannose 6-phosphate/insulin-like growth factor II receptor and transforming growth factor beta 1 levels during monoterpene-induced regression of mammary tumors. AB - The monoterpenes represent a potentially new class of breast cancer therapeutic agents. We have shown that d-limonene induces the regression of advanced rat mammary adenocarcinomas. These regressing tumors have an increased cellular concentration of both the mannose-6-phosphate/insulin-like growth factor II receptors and transforming growth factor beta 1. The terpene-induced regression of mammary tumors may result in part from the mitoinhibitory and differentiation properties of active transforming growth factor beta 1. Furthermore, the activation of transforming growth factor beta 1 in these tumors is likely to be facilitated by the increased concentration of the mannose-6-phosphate/insulin like growth factor II receptors in the mammary tumor cells. Tumors not responding to terpene therapy lacked a rise in the mannose-6-phosphate/insulin-like growth factor II receptor level which may relate to the fact that this gene is hemizygous due to maternal imprinting. PMID- 8358709 TI - Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia. AB - We have designed a single polymerase chain reaction (PCR) primer pair that detects the MLL/AF-4 fusion mRNA encoded by the derivative 11 chromosome from t(4;11)(q21;q23) leukemia cells using the reverse transcriptase PCR technique. PCR amplification was possible in seven of seven cells studied. Sequencing of the amplified products showed three different breakpoints on 11q23 and three on 4q21, resulting in six unique fusion sequences. All fusion sequences maintained an open reading frame. The areas of the MLL and AF-4 genes that are conserved in all derivative 11 fusion RNAs and therefore likely to contribute to the function of the oncogenic fusion protein are centromeric regions of MLL through exon 6 (retaining the AT hook motif) and telomeric regions of AF-4 beginning at codon 491 (containing nuclear localization and GTP-binding motifs). A single primer pair was able to detect the derivative 11 fusion transcript in seven of seven cases of t(4;11) acute leukemia tested. Given the variability shown in specific fusion sequences, studies correlating differential exon usage with clinical parameters will require different fusion-specific oligonucleotides or PCR primer pairs. PMID- 8358705 TI - Leishmaniases of the New World: current concepts and implications for future research. AB - Recent epidemiologic studies indicate that leishmaniasis in the Americas is far more abundant and of greater public health importance than was previously recognized. The disease in the New World is caused by a number of different parasite species that are capable of producing a wide variety of clinical manifestations. The outcome of leishmanial infection in humans is largely dependent on the immune responsiveness of the host and the virulence of the infecting parasite strain. This article reviews current concepts of the clinical forms, immunology, pathology, laboratory diagnosis, and treatment of the disease as well as aspects of its epidemiology and control. Recommendations for future research on the disease and its control are made. PMID- 8358710 TI - Association of putative origins of replication with the nuclear matrix in normal human fibroblasts. AB - Several metabolic processes, such as DNA organization and replication, transcription, and RNA processing are closely associated with the nuclear matrix. Nuclear matrix attachment regions are nucleotide sequences holding DNA tightly complexed with the nuclear scaffold and are resistant to extractions with detergents and high salt solutions. The role of matrix attachment regions in DNA replication has not been completely clarified, but they have been identified in close association with origins of replication in mammalian cells. We isolated nuclear matrix-associated DNA from normal human fibroblasts synchronized to different phases of the cell cycle and cloned compatible fragments into pUC19. We tested the homology of a fraction of the available clones to DNA replicated at the beginning of the S phase in human fibroblasts. We confirmed that nuclear matrix-associated DNA isolated from cells in G0 and G1 phases of the cell cycle contains sequences that are among the earliest replicated regions in the human genome. This finding supports the hypothesis that matrix attachment regions in human DNA are located in close proximity to origins of DNA replication. PMID- 8358711 TI - Transplacental carcinogenicity of cisplatin: initiation of skin tumors and induction of other preneoplastic and neoplastic lesions in SENCAR mice. AB - cis-Dichlorodiammineplatinum (cis-DDP), an anticancer agent sometimes used in pregnant women for the treatment of malignant ovarian and uterine tumors, was tested for transplacental carcinogenic and/or tumor-initiating effects in SENCAR mice. Pregnant mice were given a single i.p. injection of either cis-DDP (7.5 mg/kg body weight) in 2.5% NaCl or the same weight-adjusted volume of NaCl (5 ml/kg body weight) on day 17 of gestation. Offspring were delivered and raised by their natural mothers until weaning at 3 weeks of age. Starting at week 4, offspring in experimental groups received topical applications of 2 micrograms 12 O-tetradecanoylphorbol-13-acetate (TPA) in acetone twice a week for 20 weeks while those in control groups received only acetone (0.2 ml/application) for the same duration. The experiment was terminated at 25 weeks of age. A high incidence (18 of 37; 48.7%) of papillomas was observed in offspring exposed transplacentally to cis-DDP and postnatally to TPA, while only 10% (4 of 40) of offspring exposed to TPA alone developed such tumors (P < 0.0002). Although no skin tumors were observed without TPA promotion, transplacental administration of cis-DDP resulted in development of thymic lymphomas, lung tumors, and proliferative kidney lesions in offspring. These results provide the first evidence that cis-DDP can initiate and/or induce preneoplastic and neoplastic lesions in multiple tissues transplacentally. PMID- 8358712 TI - Alternatively spliced glucocorticoid receptor messenger RNAs in glucocorticoid resistant human multiple myeloma cells. AB - Glucocorticoids are highly effective chemotherapeutic agents used in the treatment of hematological malignancies including multiple myeloma. However, the clinical usefulness of this class of drugs is limited by the problem of resistance. In the following study, we have isolated two alternatively spliced transcripts of the glucocorticoid receptor from a complementary DNA library generated from the glucocorticoid-resistant myeloma cell line MM.1Re. In each of the clones, specific exons of the hormone binding domain are precisely deleted. Our data implicate alternate splicing as a mechanism by which a cell generates different receptor isoforms and as a consequence evades the effects of hormone. PMID- 8358706 TI - Clostridium difficile: clinical disease and diagnosis. AB - Clostridium difficile is an opportunistic pathogen that causes a spectrum of disease ranging from antibiotic-associated diarrhea to pseudomembranous colitis. Although the disease was first described in 1893, the etiologic agent was not isolated and identified until 1978. Since clinical and pathological features of C. difficile-associated disease are not easily distinguished from those of other gastrointestinal diseases, including ulcerative colitis, chronic inflammatory bowel disease, and Crohn's disease, diagnostic methods have relied on either isolation and identification of the microorganism or direct detection of bacterial antigens or toxins in stool specimens. The current review focuses on the sensitivity, specificity, and practical use of several diagnostic tests, including methods for culture of the etiologic agent, cellular cytotoxicity assays, latex agglutination tests, enzyme immunoassay systems, counterimmunoelectrophoresis, fluorescent-antibody assays, and polymerase chain reactions. PMID- 8358714 TI - Repair of O6-methylguanine and O4-methylthymidine in F344 rat liver following treatment with 1,2-dimethylhydrazine and O6-benzylguanine. AB - Concentrations of O6-methylguanine, O4-methylthymidine, and N-7-methylguanine were measured in the livers of Fischer 344 rats following treatment with 1,2 dimethylhydrazine (20 mg/kg, s.c.) alone or in combination with the O6 alkylguanine transferase inhibitor O6-benzylguanine (100 mg/kg, i.p., daily). Animals were sacrificed at 12, 24, 36, or 48 h following 1,2-dimethylhydrazine exposure. Direct measurement of alkyltransferase demonstrated that daily treatment with O6-benzylguanine completely eliminated detectable alkyltransferase activity in the livers of treated rats. Adducts in liver DNA were quantitated by high performance liquid chromatography separation followed by fluorescence detection, UV absorbance, and/or specific radioimmunological assays. In animals exposed to 1,2-dimethylhydrazine alone O6-methylguanine concentrations declined rapidly, whereas animals exposed to both O6-benzylguanine and 1,2 dimethylhydrazine showed less removal of O6-methylguanine, with significant differences between the two populations appearing at 36 and 48 h. O4 Methylthymidine removal also differed significantly between the two groups, with O6-benzylguanine-treated animals exhibiting higher concentrations of adducts at 36 and 48 h. O6-Benzylguanine treatment had no effect on the removal of N-7 methylguanine. These results show that the rate of disappearance of both O6 methylguanine and O4-methylthymidine is slower following alkyltransferase depletion, suggesting that mammalian alkyltransferase is involved in the removal of O4-methylthymidine lesions as well as O6-methylguanine lesions. PMID- 8358713 TI - Radiation-induced transforming growth factor beta and subsequent extracellular matrix reorganization in murine mammary gland. AB - Little is known about radiation-induced protein expression in vivo nor has the relationship between early molecular events and subsequent tissue repair, fibrosis, or carcinogenesis been fully appraised. In this study, expression of proteins involved in tissue remodeling was examined in mammary gland immediately and shortly after ionizing radiation exposure. Using indirect immunofluorescence, selected antigens were followed as a function of time after 0, 5, or 10 Gy of whole body gamma-radiation in the mammary gland of adult female BALB/c mice. Rapid induction of transforming growth factor beta (TGF beta) immunoreactivity was observed at 1 h post radiation. Extracellular and intracellular TGF beta increased in the periepithelial stromal sheath as evidenced by immunoreactivity with antibodies CC(1-30) and LC(1-30), respectively. Furthermore, both extracellular and intracellular TGF beta were unexpectedly expressed in the previously negative adipose stroma. Elevated expression persisted for 7 days after irradiation. Thus an early response to radiation exposure is the induction of TGF beta, which mediates myriad events during tissue repair, growth, and extracellular matrix production. The distribution of extracellular matrix proteins was examined as a function of time post radiation exposure. Collagen III immunoreactivity decreased in the periepithelial stroma at day 1. In contrast, at day 3 collagen III was newly evident in the adipose stroma, and periepithelial collagen III had increased in both abundance and intensity. By day 7 collagen III expression in the adipose stroma had resolved but was enhanced in the periepithelial stroma. Over this same period stromal collagen I immunoreactivity surrounding the epithelium became diffuse and possibly diminished. Fibronectin, laminin, and collagen IV localization were unchanged over the time course. I postulate that radiation-induced TGF beta may mediate the remodeling of the stromal extracellular matrix in the irradiated mammary gland. PMID- 8358715 TI - Chemopreventive effects of dietary D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, on initiation and postinitiation stages of diethylnitrosamine-induced rat hepatocarcinogenesis. AB - The modifying effects of dietary administration of D,L-alpha difluoromethylornithine (DFMO) during initiation or postinitiation phase on the hepatocarcinogenesis initiated by diethylnitrosamine (DEN) were investigated in male F344 rats. A total of 129 animals were divided into seven groups. Groups 1-5 were given the drinking water containing 40 ppm DEN for 5 weeks, starting at 7 weeks of age. Groups 2 and 3 were fed the diets mixed with 500 and 1000 ppm DFMO, respectively, for 7 weeks, starting at 6 weeks of age. Groups 4 and 5 were given the diets containing 500 and 1000 ppm DFMO, respectively, starting 1 week after DEN exposure and maintained on these diets until the end of the study (Week 32). Rats in group 6 were fed the DFMO diet (1000 ppm) alone during the experiment. Group 7 served as an untreated control. At the end of the study, the incidences of liver cell foci (resistant iron accumulation or positive for glutathione S transferase placental form) and hepatocellular neoplasms along with polyamine levels in the liver were measured. Also, morphometric analysis of silver-stained nucleolar organizer regions proteins as cell proliferation activity in liver cells was performed. The mean incidences and areas of foci in rats given DEN and DFMO in groups 2-5 were significantly lower than those of group 1 (P < 0.01). The frequencies of liver cell tumors in group 3 (50%), 4 (24%), and 5 (45%) were significantly reduced compared to that of group 1 (100%) (P < 0.01). The multiplicities of neoplasms in group 2 (1.15/rat), 3 (0.65/rat), 4 (0.35/rat), and 5 (0.95/rat) were significantly smaller than that of group 1 (3.34/rat) (P < 0.001). Although the polyamine levels of liver tissues among the groups showed no clear differences among the groups, the number and area of silver-stained nucleolar organizer regions proteins/nucleus in rats given DEN and DFMO (groups 2 5) were significantly lower than those of group 1. These results indicate that the feeding of DFMO during the initiation or postinitiation stage clearly inhibited DEN-induced rat hepatocarcinogenesis and that such inhibition may be due to alteration in cell proliferation activity caused by DFMO. PMID- 8358716 TI - Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid: suppressing effects on tumor development and biomarkers expression of colon tumorigenesis. AB - Our previous study has shown that dietary administration of protocatechuic acid (PCA) acts as potential chemopreventive agent in inhibiting diethylnitrosamine induced liver carcinogenesis in male F344 rats. The present study was designed to determine the modifying effect of PCA on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats and the effect on intermediate biomarkers, i.e., colonic mucosal ornithine decarboxylase activity and colonic epithelial proliferation, which can be used as effective predictors of colon cancer. Staring at 6 weeks of age, groups of animals were fed the basal diet and experimental diet containing PCA at dose levels of 250, 500, and 1000 ppm. At 7 weeks of age, all animals except the PCA alone group (1000 ppm) and untreated controls were given s.c. injections of AOM at a dose level of 15 mg/kg body weight/week for 3 weeks. PCA at 3 doses was fed during the initiation phase (before 1 week, during, and after 1 week of AOM exposure) or postinitiation phase (for 28 weeks starting 1 week after the last injection of AOM). All animals were then killed at 32 weeks after the start and colonic tumor incidence and multiplicity were determined. Animals intended for cell proliferation study were given injections of bromodeoxyuridine/5-fluoro-2'-deoxyuridine (1 ml/100 g body weight) 1 h prior to be killing. The rate of colonic cell proliferation in the distal portion was assessed by immunohistochemistry using antibromodeoxyuridine and by counting silver-stained nucleolar organizer regions protein. The colonic mucosal ornithine decarboxylase activity was also measured at the termination. The results indicate that dietary PCA administration at 500 and 1000 ppm during the initiation or postinitiation phase significantly inhibited intestinal carcinogenesis induced by AOM as revealed by the reduction of tumor incidence and multiplicity. The data also demonstrate that PCA at 500 ppm and 1000 ppm significantly inhibited bromodeoxyuridine labeling index and also silver-stained nucleolar organizer regions protein number at three doses when animals were fed PCA at the initiation or postinitiation stage. Also, feeding of PCA at 1000 ppm during the initiation and postinitiation phase exerted a pronounced inhibitory effect on the colonic ornithine decarboxylase levels. PCA feeding did not cause any toxicity. These results demonstrate that PCA is a possible new chemopreventive agent for colon carcinogenesis through the suppression of manifestation of intermediate biomarkers induced by AOM, although the precise mechanisms of PCA-induced inhibition during the initiation and postinitiation phases remain to be elucidated. PMID- 8358717 TI - Inhibitory effect of Bifidobacterium longum on colon, mammary, and liver carcinogenesis induced by 2-amino-3-methylimidazo[4,5-f]quinoline, a food mutagen. AB - The inhibitory effect of lyophilized cultures of Bifidobacterium longum on 2 amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced carcinogenesis was investigated in male and female F344 rats. Beginning at 5 weeks of age, male and female rats were divided into various experimental groups and fed one of the high fat, semipurified diets containing 0 and 0.5% lyophilized cultures of B. longum with or without 125 ppm IQ in the diet. All animals were continued on this regimen until the termination of the study. All animals were necropsied during the 58th week. The results indicated that dietary B. longum significantly inhibited the IQ-induced incidence (percentage of animals with tumors) of colon (100% inhibition) and liver (80% inhibition) tumors and multiplicity (tumors/animal) of colon, liver, and small intestinal tumors in male rats. In female rats, dietary supplementation of Bifidobacterium cultures also suppressed the IQ-induced mammary carcinogenesis to 50% and liver carcinogenesis to 27% of those observed in animals fed the control diet, but the differences did not reach a statistical significance at P < 0.05; however, the mammary tumor multiplicity (tumors/animal) was significantly (P < 0.05) inhibited in female rats fed the diet containing Bifidobacterium cultures. These findings suggest that Bifidobacterium supplements in the diet inhibit IQ-induced colon and liver tumors and to a lesser extent mammary tumors in F344 rats. PMID- 8358718 TI - Two-year carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats. AB - Tamoxifen, a nonsteroidal antiestrogen used widely in the treatment of breast cancer, was tested in a conventional 2-year carcinogenicity bioassay in rats, a species in which tamoxifen acts variably as a partial agonist and antagonist on different target tissues. Groups of 51 males and 52 females were given 5, 20, and 35 mg/kg of tamoxifen/day by gastric intubation in 0.5% hydroxypropyl methylcellulose at 5 ml/kg dose volume. There were 102 male and 104 female controls dosed with vehicle alone. Growth rate and food consumption were reduced in all treated groups. The major finding was a dose-related increase in the incidence of hepatocellular tumors which were first observed after 31 weeks of treatment in the top dose group. The majority of the neoplasms were hepatocellular carcinomas showing a well differentiated trabecular pattern. Some tumors were glandular in type. Mortality was increased in the 20 and 35 mg/kg dose groups compared with controls as a result of these tumors. By contrast, survival was greater than controls in rats given 5 mg/kg tamoxifen despite the presence of hepatocellular tumors due to a reduction in the number of pituitary tumors in females and less chronic renal disease in males. The mechanism of hepatic tumor induction by tamoxifen in rats is unclear. In view of the lack of genotoxic activity in conventional genotoxicity studies and lack of similar effect in mice or in humans, the findings may relate to a particular constellation of effects in rats. All other drug-induced changes in this study were nonneoplastic in nature and most appeared to be the result of hormonal perturbation since they were confined to endocrine organs or have been seen previously in rats treated for long periods with tamoxifen. PMID- 8358719 TI - Stimulation of growth of azaserine-induced putative preneoplastic lesions in rat pancreas is mediated specifically by way of cholecystokinin-A receptors. AB - Cholecystokinin (CCK) has been shown to stimulate the growth of both normal pancreas and azaserine-induced putative preneoplastic pancreatic lesions in the rat. The present study was performed to determine whether these effects are mediated by way of CCK-A receptors, CCK-B receptors, or both. Sixteen-day-old male Lewis rats were given i.p. injections of azaserine at 30 mg/kg body weight. Starting on day 21, rats were given s.c. injections, 5 days/week for 16 consecutive weeks, of either (a) CCK octapeptide (nonselective CCK agonist) (2.50 micrograms/kg body weight, n = 17), (b) tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2 methylphenylaminocarbonyl++ +)-Asp- (N-methyl)-Phe-NH2 (highly selective CCK-A agonist) (1.84 micrograms/kg body weight, n = 18), (c) [(2R,3S)-beta-MePhe28,N MeNle31]CCK26-33 (highly selective CCK-B agonist) (2.40 micrograms/kg body weight, n = 18), or (d) normal saline solution (control, n = 17). Rats were subsequently sacrificed, pancreatic weights were determined, and quantitative morphometric analysis of atypical acinar cell foci and nodules was performed. Both CCK octapeptide and the selective CCK-A agonist tert-butyloxycarbonyl-Trp Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 stimulated pancreatic growth and the development of acidophilic atypical acinar cell foci and nodules. Furthermore, the effect produced by the selective CCK-A agonist tert butyloxycarbonyl-Trp-Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl) Phe-NH2 was greater than that produced by CCK octapeptide. In contrast, the selective CCK-B agonist [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 had no effect. These findings suggest that the growth of putative preneoplastic lesions (acidophilic atypical acinar cell foci and nodules) in the rat pancreas during the early stages of azaserine-induced pancreatic carcinogenesis is mediated specifically by way of CCK-A receptors. PMID- 8358720 TI - Phase I trial of a 90-minute infusion of the fusion toxin DAB486IL-2 in hematological cancers. AB - DAB486IL-2, a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with interleukin-2 (IL-2), has displayed significant activity in patients with chemotherapy refractory hematological cancers. To further investigate the safety and antitumor effect of this agent, we conducted a single arm, dose escalation study of a 90-min infusion of DAB486IL-2 daily for 5 days. Patients with cancers of a histology previously reported to express the p55 component of the IL-2 receptor and who could not receive potentially more effective therapy were eligible for enrollment. Fifteen men and 8 women with a median age of 49 years were given a total of 51 courses of DAB486IL-2. The maximum tolerated dose was 0.3 mg/kg/day defined by renal insufficiency associated with hemolysis and thrombocytopenia. The clearance of DAB486IL-2 from serum fit a one-compartment model with a half-life of 11.5 +/- 4.3 (SD) min at the 0.2-mg/kg dose. Two patients sustained a partial response and 4 patients had tumor reduction not qualifying for an objective response. No tumors that were negative for expression of the p55 subunit of the receptor responded to DAB486IL-2 treatment. Reduction in size occurred in 2 tumors in which p55 expression was unknown and 4 patients with tumors that were known to be p55 positive. Dosing determined by specific activity rather than mass also appeared to be an important determinant of response. This study suggests that the presence of p55 expression on tumor cells is necessary, but alone may not be sufficient to achieve a tumor response. The correlation of additional variables such as specific activity of DAB486IL-2 and tumor expression of the p75 subunit of the IL-2 receptor and receptor function will also require further study. PMID- 8358707 TI - The Mycobacterium avium complex. AB - Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing is of increasing interest and importance as new effective antimicrobial agents are identified and evaluated. Antimicrobial resistance has already emerged as an important problem, and methods for circumventing resistance that use combination therapies are now being studied. PMID- 8358721 TI - Control of HLA-DR antigen expression by gamma-interferon: separate signal transduction mechanisms in malignant and nonmalignant human thyroid cells. AB - Three intracellular signal transduction pathways have been found to be utilized by gamma-interferon (IFN-gamma) in the induction of HLA-DR in several cell types, mainly monocytes/macrophages and B-cells: the protein kinase A (PKA); Ca(2+) calmodulin; and protein kinase C (PKC) pathways. In this study, we investigated the role of these pathways in IFN-gamma-induced HLA-DR expression in normal and neoplastic human thyroid cells. The PKA pathway seemed to inhibit both neoplastic and normal IFN-gamma-induced HLA-DR expression; addition of thyroid-stimulating hormone to normal thyroid cells, as well as 8-bromo cyclic AMP and forskolin to normal and neoplastic cells, reduced the amount of IFN-gamma-induced HLA-DR. Moreover, H-8, a PKA inhibitor, enhanced such IFN-gamma-induced HLA-DR expression. The calcium-calmodulin pathway does not seem to play a role in IFN gamma-induced HLA-DR expression in normal and neoplastic thyrocytes, since the Ca ionophore A23187, EGTA, and the calmodulin antagonist, W-7, neither induced HLA DR nor showed any effect on HLA-DR expression induced by IFN-gamma. Alone, phorbol 12-myristate 13-acetate, a PKC activator, did not induce HLA-DR on thyroid cells. However, its addition to neoplastic cells together with IFN-gamma caused a synergistic elevation of the expressed HLA-DR, whereas it significantly inhibited IFN-gamma-induced HLA-DR in normal thyrocytes. TPA had to be added before or together with IFN-gamma for optimal function. If added more than 6 h after IFN-gamma, TPA was not effective. An inactive TPA analogue did not affect HLA-DR induction, while an active analogue mimicked TPA. Staurosporine, a PKC inhibitor, reduced the TPA enhancing effect in neoplastic thyrocytes and cancelled TPA inhibition in normal cells. Moreover, when added to IFN-gamma without TPA in normal thyroid cells, staurosporine increased 3- to 4-fold the amount of HLA-DR. Thus, in normal thyroid cells the PKC pathway is activated by IFN-gamma and inhibits HLA-DR expression. In neoplastic thyrocytes, although IFN gamma does not induce HLA-DR via PKC, this pathway augments HLA-DR expression. PMID- 8358722 TI - Interaction of a polyamine analogue, 1,19-bis-(ethylamino)-5,10,15- triazanonadecane (BE-4-4-4-4), with DNA and effect on growth, survival, and polyamine levels in seven human brain tumor cell lines. AB - Computer graphics modeling and physicochemical studies of spermine-DNA interactions, as well as experiments in cell culture, indicate that a polyamine analogue with strong affinity for nucleic acids but poor ability to condense and aggregate DNA in vitro should act as an antiproliferative agent if it can enter cells. On the basis of our studies of polyamine-DNA interactions, we designed a pentamine, 1,19-bis(ethylamino)-5,10,15- triazanonadecane (BE-4-4-4-4), that had these characteristics. Measurement of melting temperature and ultraviolet light scattering studies show that the affinity of this analogue for calf-thymus DNA is about 4 times higher than that of spermine, whereas its ability to aggregate DNA is slightly poorer than that of spermine. Studies in U-87 MG, U-251 MG, SF-126, SF-188, SF-763, SF-767, and DAOY human brain tumor cells in tissue culture showed that treatment for more than 96 h with concentrations of 5 microM BE-4-4-4-4 or greater inhibited growth; decreased levels of putrescine, spermidine, and spermine; and decreased colony-forming ability in all cell lines. The cytotoxicity of the analogue varied among cell lines; DAOY and SF-767 were the most sensitive and the most resistant lines, respectively. In SF-763 cells, growth inhibition by BE-4-4-4-4 could be partially reversed by the addition of putrescine, spermidine, or spermine 1 day after BE-4-4-4-4 addition, but in U-251 MG cells, growth inhibition was reversed only by spermine and not by other polyamines. When any of the naturally occurring polyamines was added simultaneously with BE-4-4-4-4, growth inhibition was completely blocked. The data suggest that a threshold intracellular concentration of BE-4-4-4-4 is needed to manifest the growth-inhibitory and cytotoxic effects. In most cell lines, once that threshold level is reached, the growth-inhibitory and cytotoxic properties of the analogue are manifest irrespective of cellular polyamine levels. Further increases in the BE-4-4-4-4 concentration or incubation time reduce the intracellular polyamine levels but do not significantly increase growth inhibition. In U-87 MG and DAOY cells, however, prolonged incubation with higher concentrations of BE-4-4-4-4 causes additional growth inhibition along with depletion of intracellular polyamines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8358723 TI - Site-specific prodrug activation by antibody-beta-lactamase conjugates: regression and long-term growth inhibition of human colon carcinoma xenograft models. AB - Antibody-directed catalysis (ADC) is a two-step method for the delivery of chemotherapeutic agents in which enzyme-antibody conjugate, prelocalized to antigen-bearing tumor cells, catalyzes the site-specific conversion of prodrug to drug. An ADC system consisting of F(ab')-beta-lactamase conjugates and a cephalosporin derivative of the oncolytic agent 4-desacetylvinblastine-3 carboxhydrazide was investigated. The ability of the system to mediate antitumor activity was compared with that of free drug given alone and with covalent drug antibody conjugates in LS174T and T380 colon carcinoma xenografts in nude mice. Efficacy increased from moderate tumor growth inhibition by using free 4 desacetylvinblastine-3-carboxhydrazide to tumor regression and long-term stabilization with the ADC system. Labile covalent drug-antibody conjugates prepared from the same antibodies were less effective than ADC and required much higher antibody doses. The antigens KS1/4, carcinoembryonic antigen, and tumor associated glycoprotein-72, TAG-72, present on the model cell lines, were chosen to investigate the effect of differences in subcellular location and expression heterogeneity on the efficacy of ADC delivery. Response was equivalent with the three tumor antigens. Hence, heterogeneous expression and membrane shedding of carcinoembryonic antigen and TAG-72, did not diminish the suitability of these antigens as targets for ADC therapy. In contrast, drug-antibody conjugate efficacy was more sensitive to subcellular location and heterogeneity. Thus, ADC is a highly effective form of immunochemotherapy in preclinical models, with applicability toward a variety of antigen targets. PMID- 8358724 TI - Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes. AB - Incorporation of polyethylene glycol-derivatized phospholipids into liposomes results in carriers that can enhance the therapeutic efficacy of encapsulated drugs by imparting the ability to evade the reticuloendothelial system and remain in the circulation for prolonged periods. In this study, doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) is shown to completely arrest the growth of human lung tumor xenografts in severe combined immunodeficient (scid) mice. Doxorubicin administered at equivalent doses as free drug or encapsulated into conventional liposomes was ineffective at completely arresting the growth of this human tumor, although a decrease in tumor growth rate compared to untreated controls was observed. Scid mice were found to be significantly more susceptible to the toxic effects of doxorubicin than were immunocompetent C.B-17 control mice, a characteristic that is likely to result from the deficit in DNA repair mechanisms previously identified in scid mice. However, doxorubicin toxicity in scid mice could be minimized while maintaining the antitumor activity of doxorubicin encapsulated in sterically stabilized liposomes by administering the drug in multiple weekly injections at low doses. This report provides the first evidence that antitumor drugs delivered in sterically stabilized liposomes are more effective at arresting the growth of human tumors than are conventional delivery systems. In addition, the scid mouse is presented as a viable model in which to study novel chemotherapeutic approaches to the treatment of human cancer. PMID- 8358725 TI - Neuroblastoma sensitivity to growth inhibition by deferrioxamine: evidence for a block in G1 phase of the cell cycle. AB - Iron (Fe) is known to be necessary for cellular proliferation. Previous studies have suggested that neuroblastoma cells appear to be relatively sensitive to growth inhibition by a specific Fe chelator, deferrioxamine (DFO), in vitro. Also, DFO has been recently used for the treatment of neuroblastoma patients. In this paper we demonstrate that neuroblastoma cell proliferation in vitro is extremely sensitive to inhibition by DFO as compared to another cell line with almost identical growth kinetics. Neuroblastoma cells treated with DFO adapt appropriately to Fe chelation as measured by marked upregulation of transferrin receptor mRNA, increased functional transferrin receptor, and decreased cellular ferritin concentration. Further studies that quantitated cellular incorporation of 59Fe from added transferrin-59Fe in the presence of DFO indicated that neuroblastoma cells were more sensitive to inhibition of Fe incorporation by the chelator as compared to the other cell line. Neuroblastoma cells treated with DFO showed a consistent arrest in the G1 phase of the cell cycle. For cells taken from the "resting" state this block occurred before the vast majority of cells had entered S or G2-M phases of the cell cycle. Further evidence that neuroblastoma cells were arrested before the G1-S interface was provided when cells inhibited by DFO and released into aphidicolin exhibit arrest at the G1-S interface, whereas release from aphidicolin into DFO resulted in entry into S phase. Also, DFO-treated cells exhibited a decrease in both p34cdc2 immunoreactive protein as well as kinase activity. The results of these latter studies strongly indicate evidence for a Fe requirement for malignant cell proliferation before the onset of DNA synthesis. Our results also provide a basis for further studies that will better define a therapeutic approach to patients with neuroblastoma utilizing DFO treatment. PMID- 8358726 TI - Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. AB - Apoptosis is a morphologically and biochemically distinct form of cell death that occurs under a variety of physiological and pathological conditions. In the present study, the proteolytic cleavage of poly(ADP-ribose) polymerase (pADPRp) during the course of chemotherapy-induced apoptosis was examined. Treatment of HL 60 human leukemia cells with the topoisomerase II-directed anticancer agent etoposide resulted in morphological changes characteristic of apoptosis. Endonucleolytic degradation of DNA to generate nucleosomal fragments occurred simultaneously. Western blotting with epitope-specific monoclonal and polyclonal antibodies revealed that these characteristic apoptotic changes were accompanied by early, quantitative cleavage of the M(r) 116,000 pADPRp polypeptide to an M(r) approximately 25,000 fragment containing the amino-terminal DNA-binding domain of pADPRp and an M(r) approximately 85,000 fragment containing the automodification and catalytic domains. Activity blotting revealed that the M(r) approximately 85,000 fragment retained basal pADPRp activity but was not activated by exogenous nicked DNA. Similar cleavage of pADPRp was observed after exposure of HL-60 cells to a variety of chemotherapeutic agents including cis diaminedichloroplatinum(II), colcemid, 1-beta-D-arabinofuranosylcytosine, and methotrexate; to gamma-irradiation; or to the protein synthesis inhibitors puromycin or cycloheximide. Similar changes were observed in MDA-MB-468 human breast cancer cells treated with trifluorothymidine or 5-fluoro-2'-deoxyuridine and in gamma-irradiated or glucocorticoid-treated rat thymocytes undergoing apoptosis. Treatment with several compounds (tosyl-L-lysine chloromethyl ketone, tosyl-L-phenylalanine chloromethyl ketone, N-ethylmaleimide, iodoacetamide) prevented both the proteolytic cleavage of pADPRp and the internucleosomal fragmentation of DNA. The results suggest that proteolytic cleavage of pADPRp, in addition to being an early marker of chemotherapy-induced apoptosis, might reflect more widespread proteolysis that is a critical biochemical event early during the process of physiological cell death. PMID- 8358727 TI - In vitro and in vivo effect of doxorubicin combined with liposome-encapsulated muramyl tripeptide on canine monocyte activation. AB - Chemotherapeutic agents have been shown to enhance the antitumor activity of biological response modifiers and cytokines in rodents and humans. The purpose of this study was 2-fold: (a) to determine whether doxorubicin (DOX) would enhance or interfere with the effect of muramyl dipeptide and lipopolysaccharide on canine monocyte activation as measured by an in vitro WEHI-164 cell cytotoxicity assay; and (b) to evaluate the in vivo effect of DOX alone and combined with liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) on monocyte activation and serum tumor necrosis factor activity. The in vitro results showed that increasing concentrations of DOX for either 1 or 24 h incubation did not directly enhance or inhibit spontaneous or activated monocyte supernatant-mediated cytotoxicity. The in vivo study showed that monocyte supernatant-mediated cytotoxicity was increased on day 3 and significantly elevated on day 7 (P = 0.016) post-DOX (30 mg/m2, single injection) administration. When DOX was given in combination with L-MTP-PE (2 mg/m2, twice weekly for 3 weeks), monocyte-mediated cytotoxicity was enhanced on days 3 through 10 with a significant increase on day 10 (P < 0.001). In vivo monocyte supernatant-mediated cytotoxicity was significantly elevated in dogs receiving L MTP-PE alone at 2 h after day 0, 7, and 14 treatment, and this response was further enhanced by DOX. Serum tumor necrosis factor activity at 2 h post-L-MTP PE was enhanced and sustained for a longer period of time in dogs that also received DOX. We conclude that DOX administered with L-MTP-PE will enhance canine monocyte activation induced by DOX or L-MTP-PE alone, and suggest that DOX may be combined with L-MTP-PE early in the treatment of cancer patients. PMID- 8358728 TI - Unusual oxygen concentration dependence of toxicity of SR-4233, a hypoxic cell toxin. AB - Toxicity from drugs activated by bioreductive metabolism has been suggested as a means to eliminate the treatment resistance caused by hypoxic tumor cells. In general, drugs have been selected to maximize the hypoxic cytotoxicity ratio [exposure (drug concentration x time) in air:exposure in nitrogen] to cause equal toxicity. On this basis, two recently developed drugs have very similar characteristics; an aziridine derivative of misonidazole (RSU1069) and a benzotriazine di-N-oxide (SR4233). The oxygen dependence of the toxic response has not previously been characterized. This report shows that the toxicity from SR4233 extends over a much greater range of oxygen concentrations than does that of RSU1069. Furthermore, unlike all previous drugs studied, the toxicity of SR4233 does not level off at high oxygen concentrations, but continues to decrease as the oxygen concentration increases. For 1 mM oxygen (the solubility of oxygen in medium at 37 degrees C equilibrated with 100% oxygen and water vapor) the toxicity from SR4233 is at least 2000-fold less than that for hypoxia. Modeling the effect of oxygen on combined radiation and toxicity shows that radiation plus SR4233 should be much more effective in eliminating hypoxic cells than radiation plus RSU1069. The unusual oxygen dependence of toxicity by SR4233 may indicate a unique biochemical activation process. PMID- 8358729 TI - Amphibolic drug combinations: the design of selective antimetabolite protocols based upon the kinetic properties of multienzyme systems. AB - Computer simulation of a simple biochemical pathway containing a divergent branch has been used to study the interaction of two inhibitors that straddle the branch point. The combined effects of the two sequentially acting inhibitors could be synergistic, additive, or antagonistic, depending upon the regulation of the pathway. Factors that influenced the interaction included relative Vmax and Km values for the competing enzymes, the sink capacity of the system (i.e., the capacity of the system for eliminating the shared intermediate in relation to its capacity for producing it), the competitive or noncompetitive nature of the second inhibitor, and the presence or absence of feedback in the system. In certain cases, a two-fold change in the Vmax value of one of the competing enzymes was sufficient to change the interaction from synergistic to antagonistic. The existence of such drug combinations (which this article terms amphibolic combinations) means that it is possible in principle to identify binary drug combinations that will be synergistic against a tumor cell but antagonistic against normal cells. Identification of amphibolic drug combinations should be a means of designing more selective chemotherapy. PMID- 8358730 TI - Killing of skin-derived tumor cells by mouse dendritic epidermal T-cells. AB - Dendritic epidermal T-cells (DETC) are a unique population of T-cells that reside normally in mouse epidermis and express a gamma delta T-cell receptor. We have reported previously that DETC acquire in culture the capacity to lyse the YAC-1 lymphoma, a conventional target for natural killer cells. The aim of the present study was to characterize this cytotoxic potential, using a spectrum of skin derived mouse tumors. Cytotoxicity was measured by a 51Cr release assay and by the visual assessment of target cell lysis. Long-term DETC lines, established from CBA, AKR, and BALB/c mice by mitogenic stimulation and repeated feeding with interleukin 2 (5 units/ml), were used as effectors. Skin-derived tumor targets included 5 melanoma lines and the transformed keratinocyte line Pam 212. Each DETC line lysed skin-derived tumors as well as YAC-1 targets effectively in the 18-h 51Cr release assay, and target lysis occurred in a non-major histocompatibility complex-restricted manner. By contrast, freshly isolated spleen cells lysed YAC-1 but not skin tumor targets. Moreover, confluent monolayers of melanoma or Pam 212 targets were disrupted completely by added DETC lines but not by spleen cells. The cytolytic activity of DETC appeared to be specific for tumor cells, since normal mouse keratinocyte monolayers remained intact under the same conditions. Finally, DETC freshly isolated from skin failed to exhibit significant cytotoxicity but acquired this capacity 10-14 days after mitogenic stimulation and feeding with interleukin 2 (5 units/ml). We conclude that DETC possess the potential to recognize, bind, and lyse tumor cells that originate in skin. PMID- 8358731 TI - Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes: modulation of recognition through retroviral transduction of tumor cells with interleukin 2 complementary DNA and exogenous alpha interferon treatment. AB - Two cytotoxic effector cell populations were isolated from a patient with renal cell carcinoma. The tumor-infiltrating lymphocytes comprised a population of highly specific, major histocompatibility complex-restricted, cytotoxic T lymphocytes (CTL). An autologous non-major histocompatibility complex-restricted lymphokine-activated killer (LAK) cell population was generated by culturing the peripheral blood lymphocytes with high doses of recombinant interleukin 2 (rIL 2). The capacity of these two effector cell types to lyse cytokine-modulated autologous tumor cells was compared in vitro. A complementary DNA for rIL-2 was introduced into the tumor cells by retroviral transduction, and tumor cells secreting low doses of rIL-2 were isolated. The CTL recognition of these tumor cells was enhanced, compared to unmodified tumor cells, whereas LAK cell recognition was unchanged or slightly reduced. Pretreatment of tumor cells with exogenous alpha interferon led to an up-regulation of some major histocompatibility complex class I molecules and to slightly better recognition by the CTL; little effect on LAK cell recognition was observed. CTL were found to be 50-150-fold more effective than LAK cells in lysing autologous tumor cell lines or clones modulated with both rIL-2 and alpha interferon. The assessment of a patient's cytotoxic immune capacity directed against genetically modified autologous tumor cells in vitro provides important insight for cytokine-mediated gene therapy of cancer. PMID- 8358732 TI - Genotypic characterization of prostatic carcinomas: a combined cytogenetic, flow cytometry, and in situ DNA hybridization study. AB - Cytogenetic studies were performed on 36 biopsies obtained from 26 primary prostatic adenocarcinomas. Following histopathological characterization of control sections, the biopsies were investigated using metaphase cytogenetics, DNA flow cytometry, and fluorescence in situ DNA hybridization. In 12 specimens, no carcinoma was found in control sections by histopathological means. In 24 carcinoma biopsies clonal aberrations were detected in 15 specimens. Tetraploidy as sole aberration was detected in five specimens. Loss of the Y chromosome was seen in eight samples. Only one tumor revealed structural abnormalities. Eight samples were found to be normal (46,XY). Remarkably, nonclonal chromosome aberrations, particularly marked chromosome loss, were frequently detected in prostatic carcinomas and premalignant lesions (prostatic intraepithelial neoplasia). In the series of biopsies investigated by means of cytogenetics and flow cytometry, biopsies with aneuploid DNA content were found to be cytogenetically normal. Conversely, the cytogenetically aberrant clones were found to be of diploid DNA content. Evidence of focal intratumoral heterogeneity was revealed by cytogenetics, flow cytometry, and in situ hybridization. PMID- 8358733 TI - Transforming growth factor-beta 1 induces transforming growth factor-alpha promoter activity and transforming growth factor-alpha secretion in the human colon adenocarcinoma cell line FET. AB - FET cells are well differentiated human adenocarcinoma cells whose growth is partially inhibited (50-60%) by transforming growth factor-beta 1 (TGF-beta 1). In exponentially growing cultures, TGF-beta 1 induces the expression of transforming growth factor-alpha (TGF-alpha) by 3-fold. To determine whether this induction is the result of increased TGF-alpha promoter activity, FET cells were transiently transfected with a plasmid containing 2816 base pairs of the 5' flanking region of the TGF-alpha gene linked to luciferase. Transfected FET cells treated with growth-inhibitory concentrations of TGF-beta 1 (10 ng/ml) showed up to a 10-fold increase in luciferase activity. The increase in luciferase activity was dose dependent through the normal physiological range of TGF-beta 1 (0.5-20 ng/ml), saturating at 10 ng/ml. This effect was also TGF-alpha promoter specific, inasmuch as the Rous sarcoma virus long terminal repeat used as a control remained relatively insensitive to the effects of TGF-beta 1. By using progressively smaller portions of the TGF-alpha promoter region, the TGF-beta 1 responsive element was mapped between base pairs -77 and -201 of the 5'-flanking region. TGF-beta 1 treatment also affected epidermal growth factor receptor levels. FET cells treated with TGF-beta 1 (10 ng/ml) for 48 h showed a 20% decrease in the number of epidermal growth factor receptors and a 2-fold increase in the number of high affinity epidermal growth factor receptors on their surface. These results indicate that TGF-beta 1 acts as a positive regulator of TGF-alpha transcription, and they suggest a possible mechanism by which these cells circumvent the growth-inhibitory effects of TGF-beta 1. PMID- 8358734 TI - Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification. AB - Mutation of the p53 tumor suppressor gene frequently occurs in a variety of tumors including lung, breast, gastrointestinal, and brain, as well as lymphomas leukemias. Neuroblastoma, one of the most common solid tumors in childhood, often has amplification of the N-myc gene. We examined for mutations of the p53 tumor suppressor gene by single-strand conformational polymorphism using polymerase chain reaction products and direct sequencing method in neuroblastoma; in addition, we assessed the relationship between p53 mutation and N-myc gene amplification in the disease. Of 86 DNA samples from patients with neuroblastoma, two mutations (2%) were found in the coding region of the p53 gene. Each mutation caused a substitution of amino acid residues. One mutation was located in exon 5, and another was in exon 6. N-myc gene was amplified in 26% of the samples. No p53 mutations were found in neuroblastoma samples with N-myc amplification. In the two individuals, p53 mutations appeared as their disease became more progressive. The neurofibromatosis 1 (NF1) gene is frequently abnormal in another neural disorder, neurofibromatosis type 1; in addition, a potential mutational hot spot of NF1 at lysine at codon 1423 has been identified in several types of tumors. Using single-strand conformational polymorphism, we were unable to detect an abnormality in this region of NF1 in 50 samples of neuroblastoma. The data suggest that p53 mutations occasionally are associated with progression of neuroblastomas, and tumorigenetic influences of mutant p53 may differ from those of N-myc. PMID- 8358735 TI - Cloning and expression of mutant glucocorticoid receptors from glucocorticoid sensitive and -resistant human leukemic cells. AB - The molecular basis for the receptorless (r-) and activation-labile (act1) phenotypes of glucocorticoid-resistant mutants isolated from glucocorticoid sensitive human leukemic CEM-C7 cells was determined. Clones isolated from a complementary DNA library prepared from r- ICR27TK.3 cells, in which one glucocorticoid receptor (GR) gene has been deleted, contained a single adenosine to thymidine transversion in the third position of codon 753, resulting in the substitution of phenylalanine for leucine. This mutant gene (GR753F) had only 13% of the trans-activating activity of the normal gene and produced a M(r) 92,000 receptor protein with the same r- phenotype seen in ICR27TK.3 cells. Analysis of complementary DNA clones isolated from a library prepared from parental glucocorticoid-sensitive 6TG1.1 cells showed that these cells express both a normal GR gene (GR+) and the GR753F gene. Thus, their genotype is GR+/GR753F. Analysis of clones isolated from a complementary DNA library prepared from glucocorticoid-resistant activation-labile 3R7. 6TG.4 cells revealed the presence of the GR753F gene and a second mutant gene (GR421Y) containing a guanosine to adenosine transition in the second position of codon 421, resulting in the replacement of the first cysteine of the proximal zinc finger of the DNA-binding domain by tyrosine. This mutant had no trans-activating activity but normal ligand-binding characteristics. Thus, the genotype of act1 3R7.6TG.4 cells is GR421Y/GR753F. Consequently, the sequence-specific DNA-binding activity of receptors in act1 cells is attributable to the GR753F gene, while the ligand binding activity seen in intact cells is attributable to the GR421Y gene. These results provide a direct explanation for the r- and act1 phenotypes of glucocorticoid-resistant cells and demonstrate that glucocorticoid-sensitive cells derived from CEM-C7 cells contain a heterogeneous population of normal and mutant receptors. PMID- 8358736 TI - Role of chromosome 9 in human bladder cancer. AB - The tumors of 20 patients with multifocal primary transitional cell carcinoma of the bladder or lymph node metastases were examined for molecular genetic defects which we have previously found to be present in > 50% of invasive tumors. These included loss of heterozygosity (LOH) of chromosome 9, which occurs in superficial as well as invasive bladder tumors, and LOH of chromosome 17p and p53 mutations, which are commonly found only in invasive tumors. Analysis of multiple or recurrent primary tumors in 7 patients for these markers was generally consistent with recently published data that the tumors are monoclonal in origin and that p53 mutations occur as a late event in the generation of invasive bladder cancers. Comparison of the primary tumors and metastases to regional lymph nodes in 14 patients demonstrated a complete concordance between the molecular genetic defects present, showing that LOH of chromosomes 9 and 17p and p53 mutations occurred in the primary tumors before metastasis. Because of the importance of chromosome 9 in bladder cancer, we mapped the location of a putative tumor suppressor gene by restriction fragment length polymorphism analysis of 123 cases obtained in this and earlier studies. Most of the tumors showed LOH for more than one marker on chromosome 9. Results of mapping of 4 tumors with partial deletion of chromosome 9 suggests that the tumor suppressor gene is located between 9p12 and 9q34.1. PMID- 8358737 TI - Differential growth factor production, secretion, and response by high and low metastatic variants of B16BL6 melanoma. AB - Low levels of tyrosine and phenylalanine alter the metastatic phenotype of B16BL6 murine melanoma. In this study, we investigated expression and secretion of fibroblast growth factor-like (FGF-like) and transforming growth factor beta-like (TGF beta-like) molecules as well as the biological effect of basic FGF (bFGF) and TGF beta 1 on high (NDP) and low (LTP) metastatic variants of B16BL6 melanoma. Both NDP and LTP cells expressed bFGF-like and TGF beta-like polypeptides as detected by Western blot analysis. An M(r) 29,000 bFGF-like form eluted from heparin-Sepharose by 0.6 M NaCl was found in extracts of both NDP and LTP cells. Elution at 0.6 M NaCl suggested that this M(r) 29,000 form might be more closely related to FGF-5 than to bFGF. In addition, cell extracts of LTP, but not NDP cells, contained an M(r) 47,000 monomeric bFGF-like form that was not retained on heparin-Sepharose. Three major specific immunoreactive forms of M(r) 44,000, 36,000, and 29,000 were present in conditioned medium from NDP cells. The M(r) 29,000 form present in the conditioned medium of NDP cells was retained on heparin-Sepharose. Only the M(r) 44,000 and 36,000 FGF-like molecules were detected in conditioned medium from LTP cells, and they were also not retained on heparin-Sepharose. Anti-TGF beta antibody that recognized both TGF beta 1 and TGF beta 2 detected 3 different TGF beta-like forms (M(r) 25,000, 23,000 and 22,000) in NDP and LTP cell extracts. Conditioned medium from NDP cells contained an M(r) 38,000 form of TGF beta; however, no immunoreactive forms were found in conditioned medium from LTP cells. Thus, the NDP-LTP differences in this melanoma system were primarily in growth factor secretion, not expression. The effect of exogenous bFGF and TGF beta 1 on proliferation of LTP and NDP cells was determined by [methyl-3H]thymidine uptake. bFGF stimulated proliferation of NDP cells; whereas, LTP cells exhibited no increase in proliferation. Both NDP and LTP cells responded to TGF beta 1. Proliferation of NDP cells was inhibited more by this growth factor than was proliferation of LTP cells. When NDP and LTP cells were incubated with 5 ng/ml TGF beta 1 and various amounts of bFGF, the effect of TGF beta 1 was masked. Antibody depletion of bFGF-like molecules from NDP conditioned medium resulted in the decreased proliferation of NDP cells but not LTP cells. Depletion of TGF beta-like molecules resulted in increased proliferation of LTP cells but did not affect NDP cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8358738 TI - Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma. AB - A new complementary DNA, p27, has been cloned and sequenced from estradiol treated MCF7 human breast carcinoma cells. It encodes a putative highly hydrophobic protein of 122 amino acids which has a 33% overall sequence similarity to the product of the 6-16 gene (R. L. Friedman, S. P. Manly, M. McMahon, I. M. Kerr, and G. R. Stark, Cell, 38: 745-755, 1984), which is transcriptionally induced by interferons of the alpha/beta type. We demonstrate here that the p27 gene, which is located in band q32 of human chromosome 14, is also induced by interferon-alpha in human cell lines of different origin and that expression is independent of the presence of estradiol receptor in the cells. High levels of p27 RNA were found in vivo in approximately 50% of primary human breast carcinomas (21 were tested by Northern blotting). In situ hybridization to some of the p27-overexpressing tumors showed that the p27 RNA is localized in cancer cells and sometimes also in fibroblastic cells of tumor stroma. p27 RNA levels in the tumors did not correlate with the presence of estrogen receptor or with the expression of the estrogen-induced pS2 gene. Further studies are now necessary to elucidate the cause of p27 gene overexpression in breast carcinoma and in particular to determine whether it corresponds to chromosomal rearrangements in the 14q32 region and/or to induction by interferons of the alpha/beta type. PMID- 8358739 TI - Interleukin 1 alpha acts as an autocrine growth stimulator for human gastric carcinoma cells. AB - The expression and effect of interleukin 1 alpha (IL-1 alpha) were examined in human gastric carcinoma cell lines to determine if IL-1 alpha acts as a growth stimulator for these cells. Six of 8 gastric carcinoma cell lines expressed IL-1 alpha mRNA at various levels. Among them, TMK-1 and MKN-7 cells secreted IL-1 alpha into the culture fluid, in an especially large amount by MKN-7 cells. Scatchard plot analysis of IL-1 alpha binding revealed that TMK-1 cells had only one type of high-affinity receptors, whereas MKN-7 cells had high- and low affinity receptors. Cell growth and DNA synthesis of TMK-1 and MKN-7 cells were stimulated by IL-1 alpha, and those of MKN-7 were inhibited by addition of anti IL-1 alpha antibody or IL-1 receptor antagonist. The expression of IL-1 alpha mRNA by these cell lines was induced by either IL-1 alpha, epidermal growth factor, or transforming growth factor alpha. On the other hand, IL-1 alpha increased the mRNA expression for transforming growth factor alpha and epidermal growth factor receptor. These findings indicate that IL-1 alpha is an autocrine growth stimulator for gastric carcinoma cells and the interaction with epidermal growth factor/transforming growth factor alpha/receptor system should be involved in the growth modulation by IL-1 alpha. PMID- 8358740 TI - Differentiation therapy of cancer: laboratory and clinical investigations. PMID- 8358741 TI - Structural studies of the antigenic polysaccharide of Eubacterium saburreum, strain T19. AB - The antigenic polysaccharide produced by Eubacterium saburreum, strain T19, contains unusual sugars, including D-glycero-D-galacto-heptose (Hep) and D-fucose (D-Fuc). A repeating unit of the polysaccharide is composed of a linear chain of D-glycero-D-galacto-heptopyranosyl tetrasaccharide as its backbone structure, i.e., -[-->6)-beta-Hep p-(1-->3)-beta-Hep p-(1-]2-->, and a D-fucofuranosyl disaccharide as a branched group, i.e., alpha-D-Fuc f-(1-->2)-alpha-D-Fuc f-(1- >, which is linked to O-4 of one (1--6)-linked D-glycero-D-galacto-heptopyranosyl residue. The polysaccharide also contains O-acetyl groups. PMID- 8358742 TI - Proton and carbon NMR chemical-shift assignments for [beta-D-Fru f-(2-->1)]3 (2<==>1)-alpha-D-Glc p (nystose) and [beta-D-Fru f-(2-->1)]4-(2<==>1)-alpha-D-Glc p (1,1,1-kestopentaose) from two-dimensional NMR spectral measurements. AB - The proton chemical-shift assignment of nystose (1) [beta-D-fructofuranosyl-(2- >1)-beta-D-fructofuranosyl-(2-->1)-beta-D- fructofuranosyl-(2<==>1)-alpha-D glucopyranoside], was determined by using two-dimensional (2D) NMR spectral methods, and corrections of, and additions to the previous 13C chemical-shift assignments were made. The 1H peak of H-1 of the D-glucosyl group was determined by its chemical shift. Signals from fructose-1 were distinguished by the observation of long-range C-H coupling between H-1 of the D-glucosyl group and C 2 of fructose-1. The distinction between fructose-2 and fructose-3 was made by the different 1JCH coupling patterns between C-1 and H-1. Assignments of 13C and 1H chemical shifts of the related dp 5 compound, beta-D-fructofuranosyl-(2-->1) beta-D-fructofuranosyl-(2-->1)-beta-D- fructofuranosyl-(2-->1)-beta-D fructofuranosyl-(2<==>1)-alpha-D-glucopyr anoside (1,1,1-kestopentaose, 2) are also reported here with comparisons of its spectral data with the data from 1 kestose, nystose and inulin. Based on differences in 13C chemical shifts, it appears that the chemical environment of inulin is not attained in nystose, and only partially attained in 1,1,1-kestopentaose. PMID- 8358743 TI - NMR studies of oligosaccharides derived from hyaluronate: complete assignment of 1H and 13C NMR spectra of aqueous di- and tetra-saccharides, and comparison of chemical shifts for oligosaccharides of increasing degree of polymerisation. AB - A series of oligosaccharides was prepared from hyaluronate by depolymerisation with bovine testicular hyaluronidase. Complete assignment of the 1H and 13C NMR spectra was obtained for the disaccharide, the tetrasaccharide, and the NaBH4 treated tetrasaccharide, by using various 1D and 2D NMR methods. The 1H assignments for the tetrasaccharide differ from the incomplete data reported recently (ref. 11). The 13C NMR spectra of the aqueous di-, tetra-, hexa-, and octa-saccharides of this series show that all resonances, apart from those subject to obvious end effects, have chemical shifts comparable to those of the corresponding resonances of hyaluronate in D2O. The observed 13C chemical shifts suggests that cooperative intramolecular hydrogen bonds probably play a minor role in determining the conformation of hyaluronate in water. PMID- 8358744 TI - A polysaccharide produced by a mucoid strain of Moraxella nonliquefaciens with a 2-acetamido-2-deoxy-5-O-(3-deoxy-beta-D-manno-octulopyranosyl)-beta-D- galactopyranosyl repeating unit. AB - A capsular polysaccharide, isolated from the mucoid Moraxella nonliquefaciens strain 3828/60, has been investigated by component analyses, periodate oxidation, methylation analyses, mass spectrometry, 1H and 13C NMR spectroscopy, and hydrolysis to give a disaccharide that was isolated and characterised. The results showed that the polysaccharide has the repeating unit-->3)-beta-D- GalpNAc-(1-->5)-beta-Kdo p-(2-->, with approximately 40% of O-8 of Kdo being acetylated. PMID- 8358745 TI - Chemical synthesis and kinetic characterization of UDP-2-deoxy-D-lyxo-hexose("UDP 2-deoxy-D-galactose"), a donor-substrate for beta-(1-->4)-D galactosyltransferase. AB - Bovine beta-(1-->4)-galactosyltransferase (GalT) transfers galactose from UDP galactose to beta-D-GlcpNAc-terminating oligosaccharides to produce N acetyllactosamine sequences. We report here the chemical synthesis, structural characterization and enzymatic evaluation of the very labile UDP-2-deoxy-D-lyxo hexose ("UDP-2-deoxy-galactose," 2) as an alternate donor for GalT. Donor 2 had kinetic parameters, including a Km value of 51 microM, almost identical to those for the natural substrate UDP-galactose when beta-D-GlcpNAc-O(CH2)8COOMe was used as the acceptor. The product of the enzymatic transfer was isolated and confirmed to have the expected 2'-deoxy-N-acetyllactosamine sequence. PMID- 8358746 TI - Synthesis and characterization of two 1,2,3,6,2',3',4',6'-octa-O-benzoyl- beta-D hexapyranosyl-(1-->4)beta-D-allopyranoses. PMID- 8358747 TI - Isolation and purification of trehalose 6-mono- and 6,6'-di-corynomycolates from Corynebacterium matruchotii. Structural characterization by 1H NMR. PMID- 8358748 TI - Isolation and structural analysis of the tetrasaccharide 3-deoxy-5-O-[3-O- (3-O alpha-D-glucopyranosyl-L-glycero-alpha-D-manno-heptopyranosyl)-L-g lycero- alpha D-manno-heptopyranosyl]-D-manno-octulosonic acid from the core region of the lipopolysaccharide of Salmonella minnesota strain R5 (rough mutant chemotype RcP ). PMID- 8358749 TI - Conformational analysis of methyl beta-cellobioside by ROESY NMR spectroscopy and MD simulations in combination with the CROSREL method. AB - Methyl beta-cellobioside has been studied extensively by molecular dynamics (MD) simulations in water and by ROESY NMR spectroscopy in order to establish its solution structure. The MD simulations were started with four significantly different minimal energy conformations. The MD trajectories were analysed with respect to interproton distances and mobility, in order to find models for application in the analysis of NMR data. The ROESY spectra were analysed by using the CROSREL method, which allows quantitative analysis of ROESY spectra through correction for the offset dependence and incorporation of HOHAHA transfer estimates. These results were compared with data obtained from an initial rate analysis of the ROESY data and with the MD data. It is concluded that methyl beta cellobioside in aqueous solution is in the same extended conformation that is also found in the solid state. PMID- 8358750 TI - Synthesis of p-trifluoroacetamidophenyl 6-deoxy-2-O-(3-O-[2-O-methyl-3-O- (2-O methyl-alpha-D-rhamnopyranosyl)-alpha-L-fucopyranosyl]-alpha-L- rhamnopyranosyl) alpha-L-talopyranoside: a spacer armed tetrasaccharide glycopeptidolipid antigen of Mycobacterium avium serovar 20. AB - The synthesis of the title tetrasaccharide glycoside 38 is reported. p Nitrophenyl endo-3,4-O-benzylidene-6-deoxy-alpha-L-talopyranoside (4), 3-O-acetyl 2,4-di-O-benzyl-alpha-L-rhamnopyranosyl trichloroacetimidate (7), methyl 3-O acetyl-4-O-benzyl-2-O-methyl-1-thio-beta-L-fucopyranoside (15), 3-O-acetyl-4-O benzyl-2-O-methyl-alpha-L-fucopyranosyl bromide (16), and ethyl 3-O-acetyl-4-O benzyl-2-O-methyl-1-thio-alpha-D-rhamnopyranoside (33) were prepared as intermediates. Compound 4 was glycosylated with imidate 7 as well as with methyl 3-O-acetyl-2,4-di-O-benzyl-1-thio-alpha-L-rhamnopyranoside (9), affording the same disaccharide derivative 8. Deacetylation of 8 gave crystalline 17. Condensation of 17 with both fucosyl donors 15 and 16 yielded the same trisaccharide derivative 18 stereoselectively. Compound 18 was also prepared by the coupling of 4 with disaccharide glycosyl donor 20. After deacetylation of 18 (-->34), methyl triflate-promoted glycosylation with compound 33 resulted in tetrasaccharide 35. Conversion of the p-nitrophenyl group of 35 into the p trifluoroacetamidophenyl group (-->36) and removal of the protecting groups gave the title tetrasaccharide glycoside 38. PMID- 8358751 TI - Synthesis of the laminara-oligosaccharide methyl beta-glycosides of dp 3-8. AB - Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-alpha-D-glucopyranoside has been prepared in a good yield by anomerization of the corresponding beta-thioglucoside with tin(IV) chloride and transformed, in three steps, into ethyl 2-O-benzoyl-4,6-O benzylidene-1-thio-alpha-D-glucopyranoside (18). Chloroacetylation of 18, followed by treatment of the product with chlorine gave crystalline 2-O-benzoyl 4,6-O-benzylidene-3-O-chloroacetyl-beta-D-glucopyranosyl chloride (20). This was coupled with methanol in the presence of silver carbonate-silver perchlorate and the product was O-dechloroacetylated to afford methyl 2-O-benzoyl-4,6-O benzylidene-beta-D-glucopyranoside (22). Silver triflate-promoted glucosylation of 18 with 20 gave a beta-(1-->3)-linked disaccharide derivative, reaction of which with chlorine yielded crystalline O-(2-O-benzoyl-4,6-O-benzylidene-3-O chloroacetyl-beta-D-glucopyranosyl) - (1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta D-glucopyranosyl chloride (24). Likewise, condensation of 22 with 20 gave a beta (1-->3)-linked disaccharide glycoside, which was partially deprotected to give methyl O-(2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl)-(1-->3)-2-O-benz oyl- 4,6-O-benzylidene-beta-D-glucopyranoside (26). The methyl beta-glycosides of a homologous series of (1-->3)-linked beta-D-gluco-oligosaccharides from the tri- to the octa-saccharide have been synthesized in a blockwise manner by using 22 and 26 as the glycosyl acceptors, 24 as the disaccharide donor, and silver triflate as the promoter. PMID- 8358752 TI - Interpretation of dextransucrase inhibition at high sucrose concentrations. AB - When acceptor reactions were carried out at high sucrose concentrations (> or = 200 mM), dextran synthesis was inhibited and the acceptor reactions were increased. A model, based on the known mechanisms of dextran synthesis and acceptor reactions, is proposed to explain the inhibition of dextran synthesis and the increase in the acceptor products at high sucrose concentrations. According to the model, sucrose binds to a third, low-affinity binding site, allosterically changing the conformation of the active site so that dextran cannot be formed but acceptor products can be formed. PMID- 8358753 TI - Salivary gland calculi: diagnostic imaging and surgical management. PMID- 8358754 TI - Dental office record keeping and its impact on anticipated litigation. PMID- 8358755 TI - Guided tissue regeneration in the treatment of localized juvenile periodontitis- a multi-disciplinary approach in improving anterior esthetics: a case report. PMID- 8358756 TI - X-radiation: potential risks and dose-reduction mechanisms. PMID- 8358757 TI - Child abuse and neglect: the dental profession's responsibility. PMID- 8358758 TI - Dr. Kisai Takayama--the Samurai who founded Japan's first modern dental school. PMID- 8358759 TI - Removable partial denture design with a splint bar and precision attachments. PMID- 8358760 TI - Microbial assessments and periodontal diagnosis. PMID- 8358762 TI - [Transesophageal echocardiography in adults with congenital heart defects]. AB - The authors give an account of their experience with transesophageal echocardiography (TEE) in 61 adult patients with congenital heart disease. The main indications for examination in this group of patients were: confirmation of an atrial septal defect, unsatisfactory visualization, in particular in complex defects, evaluation of the results of surgical correction, detailed valvular morphology, in particular of the mitral and aortic valve, search for the source of embolization, suspected aneurysm of the aorta. A high diagnostic yield of TEE was obtained in: defects of the atrial septum, or other pathological conditions affecting the atrium, defects of the atrioventricular septum (AV), pathology of the AV valves, in particular the mitral one, pathology of the aortic valve and the efflux tract of the left ventricle, aortic arch and its descendent part, transposition of the large arteries or other complex defects, incl. conditions following surgical correction. A small diagnostic contribution of TEE was obtained when visualizing defects of the ventricular septum, pulmonary valves and the efflux tract of the right ventricle and the distal portions of the ascendant aorta. PMID- 8358761 TI - [Congenital heart defects in pregnancy]. AB - The authors investigated a group of 95 pregnant women with congenital heart disease. In two induced abortion was indicated fur cardiac reason (major left-to right shunt in ASD II and in a patient with a non-corrected TOF with a significant right-to-left shunt). In the remainder the course of pregnancy was not complicated. From the total number of 132 deliveries only six were by Caesarean section, five times on obstetric grounds. One infant died, delivery during the 29th week by Caesarean section on account of premature escape of amniotic fluid--mother with a history of radial correction of TOF. Other relevant data are summarized in a table. In the conclusion the authors summarize basic provisions indicated in pregnant women with congenital heart disease. PMID- 8358763 TI - [Basic indicators of energy metabolism in patients with rheumatoid arthritis evaluated by indirect calorimetry]. AB - The objective of the investigation was to examine basic parameters of the energy metabolism (energy expenditure at rest (REE), the respiratory quotient (RQ) and evaluate their relationship with age, basic parameters of the activity of the disease, serum positivity, basal therapy and corticoid therapy in patients with rheumatoid arthritis. The investigation comprised 26 patients with rheumatoid arthritis selected at random, incl. 12 serum positive ones. The mean age af the patients was 62.2 +/- 11.0 years, BMI 26.65 +/- 4.35, the mean duration of the disease was 11.8 +/- 9.9 years (range 1-36 years). A total of 12 patients had basal therapy, 12 patients took glucocorticoids regularly. The examination comprised a record of the case-history, clinical examination (Thompson's articular index), REE was evaluated by indirect calorimetry. The assessed REE value was compared with the expected value calculated according to Harris Benedict's empirical formula (BMR) and expressed in per cent of the calculated value (REE%). The respiratory quotient (RQ) was calculated from the assessed CO2 and O2 consumption. The authors found a close correlation between REE and REE% (r = 0.606, p < 0.01) but no correlation between BMR and REE% (r = 0.115). The above parameters did not differ in serum positive and serum negative patients with RA treated with corticoids and those without corticotherapy, only in patients with basal therapy there are statistically significantly higher REE values (6456.7 +/- 790.5 kJ/24 h vs. 5396.4 +/- 826.7 kJ/24 h, p < 0.01) and REE% (110.6% +/- 99.2%, p < 0.05), as compared with subjects without basal therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358764 TI - [Can the cardiologist implant pacemakers without a surgeon?]. AB - The authors evaluate the results of activities of the cardiostimulation centre during a two-year period: 1991-1992 with special attention to the incidence of surgical complications. As in the authors' department are implanted by cardiologists without the assistance of a surgeon, the authors compared the frequency of surgical complications with data from departments where implantations are made by a cardiologists and a surgeon. During the investigation period a total of 315 operations were performed, incl. 229 primary implantations. Early surgical complications developed in two subjects (0.63%). Late surgical complications occurred in 22 patients (6.98%). The total was thus 24 complications, i.e. 7.58% of all operations. These results are comparable with the percentage of complications reported in our literature and literature published in other countries. Permanent cardiac pacing is a routine operation which can be implemented by a well trained cardiologist without a surgeon, without a negative impact on the patient. The authors conclude that under new economic conditions this approach makes the implantation cheaper and simpler from the technical aspect. PMID- 8358765 TI - [The effect of omeprazole on healing of duodenal ulcers, Helicobacter pylori and gastritis]. AB - Losec (omeprazole) Astra Co. is a blocker of the proton pump of the parietal cell. It inhibits basal and stimulated HCl secretion. It is used for treatment of gastroduodenal ulcers, reflux oesophagitis and Zollinger Ellison's syndrome. In a group of 17 patients with duodenal ulcers the authors investigated the effect of omeprazole on (1) healing of duodenal ulcers and bulbitis after 2-4 weeks of therapy, (2) elimination of Helicobacter pylori in the antrum, (3) chronic antral gastritis. Ad 1. After two weeks of treatment the authors found that 5 of 17 chronic duodenal ulcers were healed in the remainder substantial regression was found. Four-week treatment led to healing of 16 from a total of 17 ulcers (P < 0.001), i. e. 94%. In subjects with ulcers and bulbitis (12 patients) the ulcer healed in 11 instances, in 7 patients residual bulbitis persisted. Ad 2. H. pylori was detected before treatment in 16 of 17 patients, after treatment only in 5 (P < 0.001). Ad 3. Chronic gastritis was recorded before treatment in all patients. Treatment reduced its activity and the presence of H. pylori. PMID- 8358766 TI - [Thrombosis of the inferior vena cava--an unusual cause of a chronic septic condition in a female patient with type 1 diabetes mellitus]. AB - The authors describe the accidental detection of a clinically not very marked thrombosis of the vena cava inferior in a 29-year-old female diabetic which was the cause of permanent bacteriaemia and the source of embolization of the lungs. The patient was delivered of an infant six years previously by Caesarean section, subsequently complicated by a paranephritic abscess on the right which called for surgical treatment. Since then the patient suffered from frequent dermal infections and was dyspnoic. Because of deterioration of polyneuropathic complaints of the lower extremities resulting from diabetes the patient was admitted to the authors' clinic. Sonographic examination of the abdominal cavity aroused urgent suspicion of a thrombus in the vena cava inferior, as confirmed by subsequent cavography and computed tomography. The patient was treated for prolonged periods with anticoagulants and antibiotics. During the subsequent check-up examination after four months marked diminution of the thrombus was recorded and improvement of the patient's general condition. PMID- 8358768 TI - [Ethnopharmacology and alternative medicine]. PMID- 8358767 TI - [6 "non-natural", yet most natural conditions necessary for health]. AB - The medieval preventive medical scheme which persisted up to the period of Enlightenment, called the "Six Things Non-natural and Necessary", comprised six items whose influence on the health of the individual is not inborn (not determined by innateness), but no one can avoid facing them in his life (hence, they are "necessary"); however, they may be tackled in ways either promoting or impairing health (viz.: air, food, exercise, sleep, emotions, cleansing and sexuality). The taxative list of "Six Things" is normalized in book Six of Hippocratic "Epidemics"; later, the topos was furthered by Galen, John of Alexandria (and other Alexandrinian authors) and Hunain ibn Ishaq. At least nine authors in Bohemia, Moravia and Slovakia divulged the "Six Non-natural Necessary Things" from the 15th to the end of the 18th century. Due to the re-evaluation of "naturalness" on the break from Enlightenment to Romantism, the concept of "non natural" conditions of health was abandoned; during the period of analytical medicine relevant questions were side-tracked; only the "re-synthetical" medicine (in the second half of the 20th c.) restored the original intuitive scheme of "Six Non-natural and Necessary" conditions of health in the new form of the "risk factors of health relevant behaviour". PMID- 8358769 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 8358770 TI - Monitoring of intracellular free calcium in perfused rat liver. AB - Fluorescent calcium indicators have been widely used to assess cytoplasmic calcium concentration in cells. To examine the role of calcium ions on different physiological functions (e.g. in case of liver; bile secretion, glucose metabolism, etc.) there is a need for whole organ studies. We have developed a technique to estimate intracellular free calcium changes in perfused rat liver. Krebs-Henseleit perfused livers were loaded with 7 microM or 35 microM Indo-1/AM. An area 3 mm in diameter and approximately 300 microns in depth was illuminated at 340 nm. Fluorescence was monitored with photomultiplier tubes at 3 wavelengths (400 nm for Ca-bound dye, 504 nm for free dye and 464 nm for NADH). The viability of liver preparations was assessed by measurement of the concentrations of lactate dehydrogenase and alanine aminotransferase in the effluent. Loading of the livers with 7 microM Indo-1/AM via the portal vein resulted in a 5-fold increase of fluorescence at 400 nm. However the dye 'leaked' out of the liver with a half-time of 18 min. Probenecid (a specific anion carrier blocker) inhibited loss of dye in a dose dependent fashion (2.5-10 mM). Transient calcium elevations were observed in response to vasopressin (5-50 nM) at physiological levels, ethanol (0.3-0.8 M) and the calcium ionophore, ionomycin. Certain limitations were apparent with this approach: (1) it was necessary to use an anion carrier blocker to maintain a relatively steady dye concentration; (2) endogenous NADH fluorescence interfered with the calcium signal; and (3) absolute values of calcium concentration could not be determined. PMID- 8358771 TI - Critical evaluation of cytosolic calcium determination in resting muscle fibres from normal and dystrophic (mdx) mice. AB - The fluorescent probe Fura-2/AM was used to determine cytosolic free calcium concentration in soleus muscle and in isolated flexor digitorum brevis fibres. This required a precise calibration; therefore, each calibration parameter was studied in situ. The influence of the dye concentration on calcium measurements was also examined. This precise calibration technique was used to compare absolute free calcium concentration in resting preparations from dystrophic (mdx) and control (C57) mice. We showed that the behavior of the dye was not similar in C57 and in mdx muscles. For this reason, we did not confirm the previous results that cytosolic free calcium concentration is increased in mdx muscles. PMID- 8358772 TI - Sphingosine mobilizes intracellular calcium in human neutrophils. AB - The effect of sphingosine on the cytosolic free Ca2+ concentrations, [Ca2+]i, of human neutrophils was re-examined using Fura-2 loaded cells. We found that sphingosine induced a dose-dependent elevation of [Ca2+]i. At sphingosine concentrations > or = 10 microM, the rise in [Ca2+]i was biphasic; an initial phase increasing basal [Ca2+]i by 100% was succeeded by a second phase which raised [Ca2+]i to several microM. The enhanced signal was sustained and slowly approached the Fmax of Fura-2 over 10 min. Although cytotoxicity assays indicate that Fura-2 leakage contributed to the rise in fluorescence, EGTA, surprisingly, had no effect on the time course of this response. The explanation was that EGTA blocked Fura-2 leakage from and trypan blue uptake by neutrophils. Thus, in the presence of EGTA, biphasic increases in the fluorescent signal can be attributed mainly to release of intracellular Ca2+. Mn2+ quenching studies confirmed that sphingosine mobilized Ca2+ in two distinct phases and promoted the influx of Mn2+. Mn2+ entry, however, was not matched by substantial Ca2+ influx. Sphingosine elevation of [Ca2+]i was insensitive to pertussis toxin treatment of neutrophils and was not correlated with (1,4,5)IP3 formation. Studies with semi permeabilized cells show that sphingosine, up to 80 microM, neither mobilized Ca2+ significantly nor inhibited active Ca2+ sequestration. Sphingosylphosphorylcholine induced a small but dose-dependent release of Ca2+. We hypothesize that a metabolite of sphingosine may release Ca2+ directly in intact neutrophils. PMID- 8358773 TI - An inwardly rectifying K+ channel in human adenomatous parathyroid cells. AB - The ion channel populations of cells prepared from human adenomatous parathyroid glands have been investigated using standard patch-clamp techniques with pipettes containing isotonic K(+)-rich solutions. The principal channel type observed was an inwardly rectifying K+ channel of 35 pS conductance. In addition, we have frequently observed a lower conductance (12 pS) K+ channel that appeared to conduct current in both directions. In addition to these K+ channels, we have observed non-selective cation channels and possibly CI- channels. Although we have observed occasional current transitions that might have arisen from a large conductance K+ channel similar to that observed in rat and bovine parathyroid cells, we have not been able positively to identify such a channel in human parathyroid cells, either in cell-attached or in excised inside-out patches. PMID- 8358774 TI - Placebo-controlled clinical trials with ergotamine in the acute treatment of migraine. AB - Although oral ergotamine alone or in combination with caffeine is widely used for the acute treatment of migraine, there is little evidence that it is significantly more effective than placebo. There are no placebo-controlled data to support the use of aerosol or suppository formulations. In addition, the recommended doses of ergotamine cannot be justified. Each formulation of ergotamine now should be tested in clinical studies performed according to the IHS criteria for trial design and in migraine patients fulfilling the diagnostic criteria of the IHS. Until these clinical data are available, no clear recommendations can be given for the use of ergotamine in the acute treatment of migraine. PMID- 8358775 TI - Episodic cluster headache from a textbook of 1745: van Swieten's classic description. AB - The first description of cluster headache is usually attributed to authors who published between 1867 and 1939, but lately several researchers have found accounts dating back to the 18th or even the 17th century which are incomplete or do not account for cluster headache in the strict sense. However, Gerhard van Swieten gave a full description of a case of episodic cluster headache meeting the IHS criteria in 1745, in his textbook of clinical medicine, the mainstream textbook of Continental medicine in those years, since van Swieten was the founder of the then leading medical centre, the Vienna School. That the case was found again only in 1992 is due to the circumstance that it was published in Latin. It is presented here in an English translation facing the original Latin text. PMID- 8358776 TI - Exteroceptive suppression periods in jaw-closing muscles. Variability and relation to experimental pain and sustained muscle contraction. AB - The duration of the late exteroceptive suppression period (ES2) of temporal muscle EMG activity has been reported to be reduced in patients suffering from chronic tension-type headache. Methods of recording and analysing ES2 have varied between centers and reproducibility of results within subjects, although insufficiently studied, has generally been poor. ES2 was investigated in 30 healthy subjects, using a computerized technique of recording, rectifying and averaging the EMG signals. Hour to hour and week to week variations of ES2 durations were calculated, and the influence of pain during a cold pressor test and of sustained muscle contraction on ES2 durations was investigated. The intra individual variation of ES2 durations was 16.0% from hour to hour and 20.7% from week to week. The inter-individual variation was 36.7%. The present method for analysis of ES2 periods proved to be reliable, as the intra-observer variation was 4.2% and the inter-observer variation 4.6%. ES2 periods were significantly shorter on the first compared to the second day of examination (p = 0.006) and during experimental pain (p = 0.0005). We recommend the use of the computerized average technique in future studies and caution against the dependence of results upon factors such as conditioning and pain. PMID- 8358777 TI - Basilar migraine with electroencephalographic findings of occipital spike-wave complexes: a long-term study in seven children. AB - Basilar migraine is characterized by headache preceded by prodromal symptoms and signs of posterior cerebral circulation dysfunction. Few studies have focused on EEG findings in this condition or on the prognosis of occipital spike-wave complexes observed in either migraine or epilepsy. We now report a long-term follow-up (8-16 years) in seven children affected by basilar migraine who had EEG findings of occipital spike-wave complexes. Basilar migraine resolved and the EEG became normal in all subjects during the observation period, as did migraine with aura and seizures which developed in some of the patients after basilar migraine attacks ceased. PMID- 8358778 TI - Effect of biofeedback treatment on sympathetic function in common migraine and tension-type headache. AB - Behavioral therapies such as biofeedback are commonly used to treat migraine and tension headache. Controlling sympathetic activity is effective for controlling the pain in both disturbances. A group of 26 common migraine patients and a group of 14 tension headache patients were treated by electromyographic biofeedback (EMG-BFB); blood samples were collected during the treatment (1st session; pre and post 10th session) and plasma catecholamines and cortisol measured to determine basal levels and changes induced by the behavioral therapy. The clinical efficacy of BFB treatment for tension headache and common migraine was confirmed. The basal values of the plasma stress indices were significantly different between the two groups, but did not change during treatment. The lack of correlation between the clinical improvement and the biological indices monitored indicates the need for further studies with standardized protocols in order to probe the mechanism of action of these effective behavioral therapies. PMID- 8358779 TI - Relief of cluster-tic syndrome by the combination of lithium and carbamazepine. AB - This paper presents a further case of cluster-tic syndrome. Cluster headache and trigeminal neuralgia have coexisted in our patient for 18 years. Carbamazepine has selectively relieved the tic douloureux, while lithium has completely controlled the cluster headache. Our case shows again that the simultaneous occurrence of cluster headache and trigeminal neuralgia seems to be more than coincidental. PMID- 8358780 TI - Headache resembling tension-type headache as the single manifestation of Lyme neuroborreliosis. AB - We present two patients with monosymptomatic headache resembling chronic tension type headache as the first manifestation of Lyme neuroborreliosis. The headache developed over a few days in both cases and lasted for three months in the first case and for two and a half years in the second case before the diagnosis of Lyme neuroborreliosis was made. Neuroimaging and many laboratory investigations did not lead to the diagnosis, which was only established after lumbar puncture. The CSF in both cases showed high protein, lymphocytic pleocytosis and Borrelia burgdorferi-specific intrathecal antibody synthesis. The headache disappeared completely after treatment with penicillin G. In patients suffering from daily headaches which have developed subacutely, Lyme neuroborreliosis should be considered even in the absence of signs of meningeal irritation. A lumbar puncture should be performed more often than is presently customary and the CSF should be examined for pleocytosis as well as Borrelia burgdorferi-specific intrathecal antibody synthesis. PMID- 8358781 TI - Intracranial hypertension and migraine. AB - We describe the case report of a migraineur who developed daily postural headache due to benign intracranial hypertension. The CSF pressure was elevated despite the lack of papilledema on clinical examination. This case emphasizes that intracranial hypertension without papilledema must be in the differential diagnosis of the so-called "migraine transformation" headache. Accordingly, CSF analysis, including CSF pressure measurement, should be part of the diagnostic evaluation of "migraine transformation" headache. PMID- 8358782 TI - The forgotten lumbar puncture. AB - Lumbar puncture is crucial in two distinct clinical situations in the diagnosis of the headache patient. The first is the patient who is suspected of having a symptomatic headache; the second is the patient with a chronic intractable or atypical headache disorder. This review discusses the usefulness of the lumbar puncture in the diagnosis of headache secondary to subarachnoid hemorrhage, meningitis, and intracranial hypotension and hypertension. The value of lumbar puncture in the presence of a normal CT/MRI scan is discussed. PMID- 8358783 TI - Migraine epidemiology. PMID- 8358784 TI - Endothelin in migraine. PMID- 8358785 TI - Post-endarterectomy headache. PMID- 8358786 TI - Does vasopressin serve a vasomotor adaptive function in migraine? PMID- 8358787 TI - Nuclear shuttling: the default pathway for nuclear proteins? PMID- 8358788 TI - Alternative readings of the genetic code. PMID- 8358789 TI - bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. AB - We report the isolation of bcl-x, a bcl-2-related gene that can function as a bcl 2-independent regulator of programmed cell death (apoptosis). Alternative splicing results in two distinct bcl-x mRNAs. The protein product of the larger mRNA, bcl-xL, is similar in size and predicted structure to Bcl-2. When stably transfected into an IL-3-dependent cell line, bcl-xL inhibits cell death upon growth factor withdrawal at least as well as bcl-2. Surprisingly, the second mRNA species, bcl-xS, encodes a protein that inhibits the ability of bcl-2 to enhance the survival of growth factor-deprived cells. In vivo, bcl-xS mRNA is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, bcl-xL is found in tissues containing long-lived postmitotic cells, such as adult brain. Together these data suggest that bcl-x plays an important role in both positive and negative regulation of programmed cell death. PMID- 8358790 TI - Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. AB - Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus. PMID- 8358791 TI - Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity. AB - To understand the physiological role of the creatine kinase-phosphocreatine (CK PCr) system in muscle bioenergetics, a null mutation of the muscle CK (M-CK) gene was introduced into the germline of mice. Mutant mice show no alterations in absolute muscle force, but lack the ability to perform burst activity. Their fast twitch fibers have an increased intermyofibrillar mitochondrial volume and an increased glycogenolytic/glycolytic potential. PCr and ATP levels are normal in resting M-CK-deficient muscles, but rates of high energy phosphate exchange between PCr and ATP are at least 20-fold reduced. Strikingly, PCr levels decline normally during muscle exercise, suggesting that M-CK-mediated conversion is not the only route for PCr utilization in active muscle. PMID- 8358792 TI - A kinase-independent function of Lck in potentiating antigen-specific T cell activation. AB - The lymphocyte-specific cytoplasmic protein-tyrosine kinase p56lck (Lck) is essential for T cell development and activation. Its association with the co receptor molecules, CD4 and CD8, is required for potentiation of antigen-specific signals through the T cell antigen receptor. To study the mechanism of action of Lck, hybrid molecules consisting of the extracellular and transmembrane domains of CD4 fused to Lck or other Src family kinases were analyzed in an antigen specific, CD4-dependent T cell hybridoma. Surprisingly, a chimera with a deletion of the Lck kinase domain was more active than the full-length protein. In contrast, point mutations in residues required for SH2 or kinase function resulted in moderately decreased activity, while a combination of these mutations rendered the chimera largely inactive. Different domains of CD4-associated Lck therefore have distinct functions that can independently contribute to T cell activation. PMID- 8358793 TI - Sigma F, the first compartment-specific transcription factor of B. subtilis, is regulated by an anti-sigma factor that is also a protein kinase. AB - The establishment of compartment-specific transcription in sporulating cells of B. subtilis is governed at the level of the activity of transcription factor sigma F. Genetic experiments have suggested that SpoIIAA and SpoIIAB, the other products of the sigma F operon, are involved in regulating sigma F activity. This activity is inhibited in the predivisional cell but specifically released from inhibition in the prespore about 1.5 hr after sporulation is induced. We now show that purified SpoIIAB inhibits transcription directed by sigma F in vitro. We note that the amino acid sequence of SpoIIAB shows some similarity to a group of bacterial histidine protein kinases, and we find that SpoIIAB is indeed a protein kinase that phosphorylates SpoIIAA on a serine residue. We suggest that this phosphorylation is responsible for the compartment-specific release of sigma F activity, perhaps through the formation of a tight complex between SpoIIAB and phosphorylated SpoIIAA. PMID- 8358794 TI - A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. AB - In eukaryotic cells, the accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers a signaling pathway from the ER to the nucleus. Several yeast mutants defective in this pathway map to the ERN1 gene, which protects cells from lethal consequences of stress by signaling for increased expression of BiP and other ER proteins. ERN1 encodes a 1115 amino acid transmembrane protein (Ern1p) whose glycosylated N-terminal portion is located inside microsomes and whose cytoplasmic C-terminal portion carries an essential protein kinase activity. We postulate that Ern1p is the proximal sensor of events in the ER and that binding of ligand causes transduction of information across the ER membrane, leading to activation of a specific set of transcription factors. PMID- 8358796 TI - Riding the wave of the future. PMID- 8358795 TI - Sex determination gene TASSELSEED2 of maize encodes a short-chain alcohol dehydrogenase required for stage-specific floral organ abortion. AB - Maize produces separate unisexual flowers through programmed abortion of preformed organ primordia. In the male inflorescence (tassel), stamen primordia develop to sexual maturity, while gynoecia (pistil primordia) are aborted. In tasselseed2 (ts2) mutant plants, floral structures in the tassel adopt a female developmental program. Here we report the transposon tagging and cloning of the TS2 gene, which plays a late but pivotal role in determining the sexual fate of floral meristems. Shortly before abortion of the gynoecium, Ts2 mRNA is expressed subepidermally in that primordium. Phenotypic instability of the Activator (Ac) induced allele ts2-m1 indicates that late restoration of TS2 action in somatic tissues, which is correlated with Ac excision, reactivates the male developmental program. The predicted amino acid sequence of the Ts2 protein shows significant similarity to short-chain alcohol dehydrogenases, particularly hydroxysteroid dehydrogenases. PMID- 8358797 TI - Communication is the key. PMID- 8358798 TI - Hospital admittance, operating room technique and discharge of the dental patient. PMID- 8358799 TI - Investing for the established practice. PMID- 8358801 TI - The spousal aspects of retirement. PMID- 8358800 TI - Marketing for today's dentist. PMID- 8358802 TI - What do a leech and a handpiece have in common? PMID- 8358803 TI - Temporomandibular joint osteoarthrosis: clinical and radiographic characteristics 30 years after nonsurgical treatment: a preliminary report. AB - Thirty years after being treated nonsurgically for osteoarthrosis and internal derangement, 14 women and seven men were re-examined clinically and radiographically. The results of this examination were compared with those recorded before and after treatment 30 years ago, and with those of a matched control group. The number and degree of subjective and objective signs and symptoms decreased, and was comparable to that of the controls. However, the patients reported significantly more pain and difficulty on opening the mouth wide. This was reflected in the radiographically assessed joint mobility, which increased significantly over the years, but was still significantly less than that of the controls. The occurrence and extent of radiographically visible osteoarthrotic alterations increased over the years, and differed significantly from those of the controls. Therefore, the authors conclude that few symptoms and clinical signs of osteoarthrosis are found many years after treatment, although radiographic alterations may be extensive. PMID- 8358804 TI - Myofascial pain dysfunction: treatments used by ADA members. AB - A survey of 10,000 members of the American Dental Association was conducted in order to identify the most commonly used treatments for myofascial pain dysfunction (MPD). A questionnaire was used in which MPD was defined, all treatments (including referral) were listed, and a percentage-of-use estimate for each treatment was requested. Results from 2,544 questionnaires showed that the most commonly used treatments are: flat plane splints with anterior/canine guidance or posterior group function, occlusal equilibration, thermal packs, relaxation/stress management training, diet counseling, and medications with anti inflammatory (nonopioid) analgesic and muscle relaxant properties. The results also showed considerable variation in the ways common treatments are performed. A call is issued for systematic and careful research on the outcomes of these and other treatments and their major variations. PMID- 8358805 TI - Head and cervical spine postures in complete denture wearers. AB - Signs and symptoms in the stomatognathic system and head and cervical spine postures were evaluated in 10 edentulous patients prior to renewal of their dentures, as well as immediately and six months after insertion of new dentures. Natural head posture was recorded using the fluid-level method and measured from the roentgen cephalograms. It was shown that the variables duration of edentulousness and free-way space displayed positive correlations with the dysfunction symptoms. In addition, the patients who needed oral rehabilitation the most, who received the greatest reduction in their free-way space, were seen to have raised their heads more than average. There was also an inverse correlation between the reduction of clinical dysfunction index score and cervical spine postures. PMID- 8358806 TI - Headache and facial pain-the role of the paranasal sinuses: a literature review. AB - Long neglected as a clinical entity, sinus headache has become a common complaint of patients with facial pain. Although pain is associated with some sinus disease, many experts feel the magnitude and instances of sinus headache have been exaggerated to the public. Birt stated that "otolaryngologists see scores of patients with vague discomfort in the forehead, between the eyes, and across the nose and cheeks." Patients invariably ascribe their symptoms to sinus disease, and are later surprised to discover that they are not infected. In fact, chronic sinusitis is not particularly common, and many headache patients with autonomic features will probably have muscle tension headaches or migraines. Most authors feel that acute or chronic headache processes are not a result of overt paranasal sinus disease. However, the clinician is obliged to consider the possibility in differential diagnosis. This paper will present the anatomic, neurologic, physiologic, and pathologic aspects of paranasal sinus disease and its conceivable relationship to headache and facial pain. PMID- 8358807 TI - The effects of dental condition on hand strength and maximum bite force. AB - Piezoelectric force transducer and hand dynamometer were used for measuring the maximum bite force and hand grasp force on 2034 primary, middle, and high school students. Dental condition and body weight and height were also observed to relate to the force measurements. It was discovered that both forces increased relative to the increase of age, body weight, and body height. Boys had stronger bite force than girls at all age groups, while the grasp force of boys became significantly stronger only after the age of 13. Students who had dentition with decay and missing teeth tended to have weaker bite force, while hand force was not influenced. Bite force does not seem parallel to hand strength and is, instead, related to dental condition. PMID- 8358809 TI - A system for the study of jaw movements. AB - This paper describes a system to record incisal and condylar movements. It consists of two Charge Coupled Device (CCD) cameras that detect the position of markers fixed to the face, real-time hardware to recognize the markers and software for three-dimensional reconstruction of condylar and mandibular movements. The subject sat upright in front of the cameras and was asked to perform jaw movements. The position of the markers was recorded and the coordinates were fed into the computer and converted to three-dimensional kinematic data by a mathematical algorithm implemented on an AT IBM personal computer. Dedicated software calculated the head movements and the mandibular movements separately and performed a three-dimensional mathematical reconstruction of the movements of the condylar points and the interincisive point, using the geometrical rules of a rigid body. This pilot study describes the pattern from opening, closing, protrusive, and lateral movements as obtained from healthy subjects with good dentition. PMID- 8358808 TI - A clinical observation: a relationship of occlusal contacts to distal musculature. AB - Dentists treating craniomandibular dysfunction frequently encounter pain and dysfunction in seemingly unrelated distal areas of the body. This is a study using manual palpation to demonstrate a change in distal muscle pain response caused by altering an apparent noxious tooth contact. Forty-four (n = 44) patients with a defined muscle involvement were selected for this study. After isolating one tooth and the single contact that influenced the muscles under observation, one or two slight alterations were made to the contact to redirect the occlusal force in all but the four control subjects. Thirty-eight (n = 38) patients showed marked relief in tenderness to palpation following minute tooth alteration in the muscles being observed. Two (n = 2) showed slight improvement. No significant change in pain to palpation was noted in the control group (n = 4). The results suggest that altering an apparent noxious occlusal contact has a direct influence on muscles in other parts of the body. PMID- 8358810 TI - Pressurized infusion of sodium hyaluronate for closed lock of the temporomandibular joint. Part I: A case study. AB - Patients with temporomandibular joint disorders (TMD) report a myriad of problems including headaches, facial pain, limited mouth opening capacity, and clicking and/or grating sounds from the temporomandibular joints. Although conservative therapy with an occlusal splint can bring relief for many of these patients, a small number of subjects must be treated by means of surgical procedures. Direct injections of either air or fluids (saline, local anesthetic, corticosteroid, hyaluronate) into the superior and/or inferior temporomandibular joint (TMJ) cavities have gained popularity. The injection of a local anesthetic and hyaluronic acid can provide relief for patients with persistent, painful nontranslatory closed-lock conditions of the TMJs. As documented through objective electronic and computer-enhanced measurements, this case report describes the effect of sodium hyaluronate on a closed lock condition of the TMJ. This case report explains the methodology employed for a larger group of closed lock patients treated and monitored for over one year. The results of that larger group will be reported at a later time after long-term efficacy is confirmed. PMID- 8358812 TI - Scuba diving and TMD. PMID- 8358811 TI - A clinical study of temporomandibular joint (TMJ) vibrations in TMJ dysfunction patients. AB - Using electrovibratography (EVG), the vibrations of 309 temporomandibular joints (TMJs) from 213 patients with clinical symptoms of temporomandibular joint dysfunction (TMD) were compared to TMJ arthrography. Of 309 imaged joints, 221 had an internal derangement (ID) and 88 were arthrographically normal (NID). Among the parameters derived from the power spectrum function of joint vibration, the total power density from 0 to 600 Hz (I(T)), the peak power density I(max)), and the power density at each 50 Hz frequency range (I(f)), each of these was significantly greater in ID than in NID patients. The frequency range that included (I(max) and the frequency range containing 50%, 75%, and 90% of I(T) was significantly lower in ID than in NID patients. The diagnostic sensitivity and specificity of a patient's perception of TMJ sounds were 43% and 80%, respectively, while those for a doctor's perception were 54% and 72%. When using I(T) as a parameter, the sensitivity and specificity of the EVG were 75% and 77%, respectively. By using these parameters of TMJ vibration energy analysis, a separation may be made between patients with normal joint anatomy and internal derangement. PMID- 8358813 TI - Capsulitis of the temporomandibular joint. PMID- 8358814 TI - History taking of the facial pain patient with the assistance of a comprehensive questionnaire. PMID- 8358815 TI - Asd-homothallism of Saccharomyces cerevisiae: identification of asd1-1 as an allele of sir4 and detection of alpha-specific suppressors of it. AB - Asd-homothallism of Saccharomyces cerevisiae involves a life cycle characterized by a non-mating phenotype and endomitotic diploidization. The former trait is determined by a single mutation, asd1-1. This mutation was mapped between hom2 and lys4 on the right arm of chromosome IV and was complemented by the cloned SIR4 gene. Therefore, we conclude that asd1-1 is an allele of sir4-11 and renamed it sir4-11. Endomitotic diploidization of asd-homothallism is caused by the collaboration of three to four mutations including sir4-11. In the course of this study, we detected alpha-specific suppressors of sir4-11. PMID- 8358816 TI - Major chromosomal length polymorphisms are evident after meiosis in the phytopathogenic fungus Leptosphaeria maculans. AB - Chromosomal DNA of Australian field-isolates of the phytopathogenic ascomycete Leptosphaeria maculans was resolved by pulsed-field gel electrophoresis. All isolates examined had highly variable karyotypes. Ascospores (sexual spores) derived from single pseudothecia (sexual fruiting bodies) isolated from Brassica napus (oilseed rape) stubble were analyzed. In two tetrads four distinct karyotypes were observed, with only one chromosomal DNA band in common to all the members of each tetrad. Although isolates had highly variable karyotypes, two overall patterns were present. In one pattern there were at least 12 chromosomal DNA bands, the largest being greater than 2.2 Mb in size; in the other there were more than 15 chromosomal DNA bands, the largest being about 2.0 Mb. The chromosomal DNA preparations included mitochondrial DNA which migrated as a diffuse band between 0.10 and 0.15 Mb in size, and DNA molecules of 8 and 9 kb in size. PMID- 8358818 TI - Symmetrical transcription in the tRNA region of the mitochondrial genome of Saccharomyces cerevisiae. AB - The occurrence of discrete transcripts originating from the non-coding strand of the yeast mitochondrial genome is described. The region under investigation is localized in the large tRNA gene cluster between the LSU ribosomal RNA and OXI 1 genes. The transcripts originating from the non-coding strand were detected in a wild-type strain and in a rho- mutant. Their size range includes transcripts of about 2000 nucleotides able to accommodate more than one "anti-tRNA". In some cases their extremities can be mapped near highly-conserved nonanucleotides that could function as origins of transcription. The involvement of the tRNA processing machinery in the cleavage of these transcripts is also hypothesized. PMID- 8358817 TI - A nucleotide sequence involved in replicative transformation of a filamentous fungus. AB - Replicative plasmids generated through in-vivo recombination have been identified among transformants of the fungus Pleurotus ostreatus. In addition to sequences from a standard selection vector (pAN7-1), these recombinant plasmids contain recombined sequences of chromosomal origin conferring replicative potential upon the vector. One such recombined sequence, an 1148-bp insert into plasmid pP01, has been characterized. This sequence has been analyzed for secondary structural features as well as for consensus sites affiliated with origins of replication (ori) in other eukaryotic systems. The 1148-bp insert lacks an ORF and does not contain an acceptable match to the commonly identified 11-bp ars consensus sequence (A/TTTTATA/GTTTA/T) for autonomous replication in the yeast Saccharomyces cerevisiae. The analysis, however, revealed a cluster of three hairpin-loop-forming subsequences with individual delta G25 degrees C free energy values of -7.6, -6.4 and -5.2 kcal mol-1. Also found were two 7-bp analogues to centromere-affiliated sequences recognized in other fungi, as well as several putative gyrase recognition sites comparable to the 9-bp S. cerevisiae/E. coli gyrase-binding consensus sequence. Sequences comparable to the ori of the yeast 2 microns plasmid or to various sequences associated with ori of yeast/fungal mitochondrial DNAs (mtDNA) were not present in the 1148-bp insert. Replication of pP01 appears rather to involve a replication of chromosomal derivation devoid of an ars-type consensus. PMID- 8358819 TI - Characterization of a second nuclear gene, AEP1, required for expression of the mitochondrial OLI1 gene in Saccharomyces cerevisiae. AB - Due to mutation in a single nuclear locus, AEP1, the temperature-conditional pet mutant ts1860 of Saccharomyces cerevisiae fails to synthesize mitochondrial ATP synthase subunit 9 at the restrictive temperature of 36 degrees C. The presence at this temperature of near-normal levels of the cognate oli1 mRNA in mutant ts1860 indicates that, as previously shown, the product of the AEP1 gene is required for translation of the mitochondrial oli1 transcript. In this study the AEP1 gene has been cloned from a wild-type yeast genomic library by genetic complementation of a temperature-conditional aep1 strain at the restrictive temperature. A 2,330-bp genomic fragment which restores subunit 9 synthesis in aep1 mutant strains was characterized. This fragment encoded five open reading frames: the longest of these, at 1,554 nucleotides, was identified as the AEP1 gene, since disruption of this reading frame generated a non-conditional pet strain unable to synthesize subunit 9. The predicted product of AEP1 is a basic, hydrophilic protein of 59,571 Da which possesses a putative mitochondrial address sequence. Hybridization studies with AEP1-specific probes indicate that the gene is located on chromosome XIII and produces several poly(A)+ transcripts ranging in size from 0.9 to 2.7 kb. None of the identified reading frames share significant homologies with entries of several data bases. PMID- 8358820 TI - Molecular cloning and analysis of the nuclear gene MRP-L6 coding for a putative mitochondrial ribosomal protein from Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae nuclear gene MRP-L6 was cloned by complementation of the respiratory-deficient mutant pet-ts 2523 with a library of wild-type yeast genomic DNA. The isolated gene was part of a 3.8-kb sequenced DNA fragment containing, in addition to MRP-L6, two unassigned reading frames, ORF1 and ORF2. MRP-L6 codes for a basic protein of 205 amino acids and a molecular mass of 22.8 kDa. The protein exhibits significant sequence similarity to the ribosomal protein L6 of bacteria and chloroplasts. Unlike the corresponding bacterial proteins, however, the MRP-L6 protein (MRP-L6p) contains at its N-terminus a 16 amino-acid leader sequence exhibiting the known characteristics of mitochondrial import signals. Disruption of MRP-L6 leads to the phenotype of a mitochondrial translation-defective, rho-negative yeast mutant. The results are consistent with MRP-L6p representing an essential component of yeast mitochondrial ribosomes. Expression of MRP-L6 was examined, under conditions of glucose repression and derepression, in wild-type cells and in a series of catabolite repression defective yeast mutants. In most cases, a distinct though small influence of the carbon source on the expression of an MRP-L6/lacZ reported construct was observed. PMID- 8358821 TI - The cytoplasmic male-sterility (CMS) determinant of common bean is widespread in Phaseolus coccineus L. and Phaseolus vulgaris L. AB - To identify regions of the mitochondrial genome that potentially could specify cytoplasmic male sterility (CMS) in Phaseolus coccineus (including P. polyanthus), and to define differences amongst P. coccineus lines, mitochondrial (mt)DNA restriction patterns and Southern blots of total DNA from sterile and fertile lines were analysed. By restriction endonuclease mapping we isolated a region which was specific to CMS lines flanking an F1-ATPase alpha-subunit (atpA) gene. DNA sequence analysis of this region showed 99.9% homology to the region previously isolated from P. vulgaris CMS Sprite. A high frequency of plants carrying the CMS-fragment was observed in a wild Phaseolus population, perhaps explaining the occurrence of inter- and intra-specific gene flow observed in the autogamous species P. vulgaris. PMID- 8358822 TI - Characterization of the radish mitochondrial orfB locus: possible relationship with male sterility in Ogura radish. AB - The orfB locus of the normal (fertile) and Ogura (male-sterile) radish mitochondrial genomes has been characterized in order to determine if this region, which has previously been correlated with cytoplasmic male sterility (CMS) in Brassica napus cybrids (Bonhomme et al. 1991; Temple et al. 1992), could also be involved in radish CMS. In normal radish, orfB is expressed as a 600 nucleotide (nt) transcript. In Ogura radish, orfB is present as the second gene of a 1200-nt transcript that also contains a 138-codon open reading frame (orf138). Sequences showing similarity to orf138 are present in normal radish, but are not expressed. PMID- 8358823 TI - The sugar beet mitochondrial gene for the ATPase alpha-subunit: sequence, transcription and rearrangements in cytoplasmic male-sterile plants. AB - We have characterized the mitochondrial atpA (the alpha subunit of F1-ATPase) gene from male-fertile cytoplasm (cv TK81-0) of sugar beet. The gene is 1518-bp long and encodes a polypeptide of 506 amino acids. The atpA mRNA sequence is modified by three C-to-U RNA editing events, all of which alter the encoded protein sequences. In order to examine the genome organization of the atpA locus in cytoplasmic male-sterile (CMS) sugar beet, atpA-containing clones were isolated from Owen CMS (TK81-MS) and a different source of CMS [I-12CMS(2)] cytoplasm respectively. The sequences of the atpA coding region from TK81-MS and I-12CMS(2) are identical to each other and to the corresponding TK81-0 sequence. However, the TK81-0 and TK81-MS loci diverge completely 47 bp upstream of the initiation codon, resulting in different 5' transcript termini for the two genes. On the other hand, the point of divergence between the TK81-0 and I-12CMS(2) atpA genes was found to occur after 393 bp 3' to the TAA stop codon. Our results also show the 3'-flanking sequences of I-12CMS(2) atpA to be present elsewhere in the mitochondrial genomes of TK81-0, TK81-MS and I-12CMS(2), suggesting the possible involvement of these repeated DNA elements in the sequence rearrangements. PMID- 8358825 TI - Detection of gene-disruption events in Aspergillus transformants by polymerase chain reaction direct from conidiospores. AB - We describe a rapid method for the identification of gene disruption events after DNA-mediated transformation of Aspergillus fumigatus. This involves a polymerase chain reaction in which the target DNA is added in the form of intact conidiospores. Using one primer specific to the plasmid DNA and a second primer specific to the target gene on the chromosome, it is possible to identify gene disruption events among the more common ectopic integrations approximately 4 h after sporulating transformants appear on selective medium. PMID- 8358826 TI - Reorientation of the distal region in linkage group IIR of fission yeast. AB - The genetic map of the fission yeast Schizosaccharomyces pombe has been revised in the distal region of chromosome arm IIR. The spo4 locus, hitherto considered the outermost marker, has been moved to an intermediate position. As a result, and in accordance with recent physical mapping data, the order of the entire distal subgroup of some 12 genetic markers is reversed relative to previously published gene maps. PMID- 8358824 TI - A large deletion in the plastid DNA of the holoparasitic flowering plant Cuscuta reflexa concerning two ribosomal proteins (rpl2, rpl23), one transfer RNA (trnI) and an ORF 2280 homologue. AB - We have determined the nucleotide sequence of a 5.3-kb region of the plastid DNA (ptDNA) from the heterotrophic holoparasitic plant Cuscuta reflexa. The cloned area contains genes for the D1-protein (32-kDa protein; psbA), tRNA(His) (trnH), ORF 740 (homologous to ORF 2280 from Nicotiana tabacum), ORF 77 (homologous to ORF 70), tRNA(Leu) (trnL) and a hypothetical ORF 55 which has no homology to any known gene among higher plants. This 5.3-kb area is colinear with a 12.4-kb region of tobacco ptDNA and has therefore undergone several deletions totalling 7.1 kb. Most of the missing nucleotides belong to one large deletion in the ptDNA of C. reflexa of approximately 6.5 kb. This deletion involves two ribosomal protein genes, rpl2 and rpl23, as well as the transfer RNA for Isoleucin (trnI) and a region encoding 1540 amino-acid residues of an ORF 2280 homologue, as compared to tobacco chloroplast DNA. This is remarkable since the remaining genes, especially the psbA gene, are highly conserved in C. reflexa. Furthermore, we found that the expression of the psbA gene is in the same range as in the autotrophic Ipomoea purpurea which belongs to the same family as Cuscuta (Convolvulaceae). Here we hypothesize a total loss of rpl2 and rpl23 in the entire genome of C. reflexa. The phylogenetic position of, and the evolutionary change of ptDNA from, Cuscuta are discussed. PMID- 8358827 TI - High efficiency transformation of Kluyveromyces marxianus by a replicative plasmid. AB - Kluyveromyces marxianus can be transformed with an efficiency of 10(5) transformants/microgram of DNA by a replicative plasmid using electroporation. In order to obtain this efficiency, we isolated ura- mutants cells which can be complemented by the URA3 gene from Saccharomyces cerevisiae. The URA3 gene and KARS2, a replicative origin from Kluyveromyces lactis which functions in K. marxianus, were ligated together in a plasmid which can be used as a vector to transform this strain. PMID- 8358828 TI - The glycerol kinase (GUT1) gene of Saccharomyces cerevisiae: cloning and characterization. AB - The GUT1 gene of Saccharomyces cerevisiae, encoding glycerol kinase, was cloned and sequenced. The cloned genomic DNA fragment contains an open reading frame potentially coding for a protein of 709 amino acids with homology to bacterial glycerol kinases (40.8% identity over 502 amino acids, and 42.1% identity over 496 amino acids, in comparison to the smaller E. coli and B. subtilis enzymes). Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media. No glycerol kinase activity was detected in the disruption mutant. According to enzyme activity and transcript analysis, synthesis of glycerol kinase is repressed by glucose, and derepression is ADR1 dependent. PMID- 8358829 TI - Expression of the Klebsiella pneumoniae pullulanase-encoding gene in Saccharomyces cerevisiae. AB - A 3800-base pair (bp) DNA fragment encoding the mature pullulanase from Klebsiella pneumoniae was inserted between two different yeast expression secretion cassettes and an yeast gene terminator. These cassettes were cloned into an yeast centromeric plasmid YCplacIII and transformed into laboratory strains of Saccharomyces cerevisiae. Transcription initiation signals were derived from the mating pheromone alpha-factor (MF alpha 1p) and alcohol dehydrogenase (ADC1p) gene promoters. Secretion of pullulanase was directed by the leader sequence of the yeast mating pheromone alpha-factor (MF alpha 1s). Transcription termination was effected by the yeast tryptophan synthase gene terminator (TRP5T). Southernblot analysis confirmed the presence of pulA in transformed yeasts and Northern-blot analysis revealed the presence of PUL1 mRNA. A pullulan agarose assay indicated the extracellular production of biologically active pullulanase by S. cerevisiae. PMID- 8358830 TI - Cloning and expression of Hormoconis resinae glucoamylase P cDNA in Saccharomyces cerevisiae. AB - A cDNA coding for glucoamylase P of Hormoconis resinae was cloned using a synthetic oligonucleotide probe coding for a peptide fragment of the purified enzyme and polyclonal anti-glucoamylase antibodies. Nucleotide-sequence analysis revealed an open reading frame of 1848 base pairs coding for a protein of 616 amino-acid residues. Comparison with other fungal glucoamylase amino-acid sequences showed homologies of 37-48%. The glucoamylase cDNA, when introduced into Saccharomyces cerevisiae under the control of the yeast ADC1 promoter, directed the secretion of active glucoamylase P into the growth medium. PMID- 8358831 TI - Polyploidy in the haplontic yeast Schizosaccharomyces pombe: construction and analysis of strains. AB - The fission yeast Schizosaccharomyces pombe has a haplontic life cycle in which the diplophase is confined to the zygote. Through the use of one- and two-step protoplast fusions we show that the ploidy can be increased up to pentaploid. The polyploid fusion products are rather unstable and segregate cells of lower ploidies by gradual loss of chromosomes during mitotic divisions. The polyploid cells conjugate normally but are prone to arrest at various stages of meiosis (1 , 2- and 3-spored asci, binucleate spores) and/or produce inviable, most probably aneuploid, spores. Marker segregation in the complete tetrads indicates the multiple association of homologous chromosomes. In tetra- and penta-ploid meiosis, multispored (6- to 7-spored) asci are also produced, probably by postmeiotic division of the nuclei. PMID- 8358832 TI - Cloning of an Aspergillus niger invertase gene by expression in Trichoderma reesei. AB - The filamentous fungus Aspergillus niger produces two glycosylated forms of the sucrose-hydrolysing enzyme, invertase. In contrast, some Trichoderma species lack invertase and are unable to utilise sucrose as a sole carbon source. Using an A. niger genomic library constructed in a cosmid vector containing the ura5 gene of Podospora anserina as a selectable marker, and the T. reesei ura5- strain as a sucrose-minus recipient strain, an A. niger invertase gene (suc1) has been cloned by a sib selection procedure. PAGE and enzyme analysis confirmed that transformants had acquired invertase activity. The cloned gene contained DNA sequences which were complementary to the amino-acid sequences of tryptic peptides found in invertase purified from A. niger. The suc1 invertase gene can be used as a dominant selectable marker for the transformation of Trichoderma strains. PMID- 8358833 TI - Purification and characterisation of an Aspergillus niger invertase and its DNA sequence. AB - A secreted invertase was purified 23-fold by ultrafiltration, ion-exchange, and gel filtration chromatography from the culture supernatant of 18 h sucrose-grown cultures of Aspergillus niger. The purified enzyme hydrolysed sucrose and raffinose but there was no detectable hydrolysis of inulin, melezitose or PNPG. Invertase activity was optimal at pH 5.5 and 50 degrees C. The molecular mass of reduced invertase was 115 kDa, as determined by SDS gel electrophoresis. The native molecular weight of between 225 kDa and 250 kDa, estimated by electrophoresis under non-denaturing conditions, suggests that the protein is a dimer of identical subunits. The suc1 gene encoding this protein was completely sequenced. The translated sequence yields a protein of 566 amino acids with a calculated molecular mass of 61 kDa, suggesting that carbohydrates represent about 50% of the mass of the protein. PMID- 8358834 TI - uvsI mutants defective in UV mutagenesis define a fourth epistatic group of uvs genes in Aspergillus. AB - Three UV-sensitive mutations of A. nidulans, uvsI, uvsJ and uvsA, were tested for epistatic relationships with members of the previously established groups, here called the "UvsF", "UvsC", and "UvsB" groups. uvsI mutants are defective for spontaneous and induced reversion of certain point mutations and differ also for other properties from previously analyzed uvs types. They are very sensitive to the killing effects of UV-light and 4-NQO (4-nitro-quinoline-N-oxide) but not to MMS (methylmethane sulfonate). When double- and single-mutant uvs strains were compared for sensitivity to these three agents, synergistic or additive effects were found for uvsI with all members of the three groups. The uvsI gene may therefore represent a fourth epistatic group, possibly involved in mutagenic repair. On the other hand, uvsJ was clearly epistatic with members of the UvsF group and fitted well into this group also by phenotype. The uvsA gene was tentatively assigned to the UvsC group. uvsA showed epistatic interactions with uvsC in all tests, and like UvsC-group mutants is UV-sensitive mainly in dividing cells. However, the uvsA mutation does not cause the defects in recombination and UV mutagenesis typical for this group. PMID- 8358838 TI - [Promotion, encouragement and support of breast feeding]. PMID- 8358836 TI - Physical characteristics of the genome of the phytopathogenic fungus Puccinia graminis. AB - The physical characteristics of the genome of Puccinia graminis f. sp. tritici, the wheat stem rust fungus, were determined by reassociation kinetics. The results indicate that the haploid genome contains 67 Mb and consists of three classes of DNA sequences: (1) 64% unique; (2) 30% repetitive; and (3) 4% foldback. The repetitive sequences have a total complexity of 390 kb and are repeated an average of 52 times. The base composition was 45.3% G+C based on an analysis of the DNA melting temperature. The average amount of DNA per ungerminated urediniospore by diphenylamine assay, corrected for losses during extraction, was 435 fg. This was three times the expected value (147 fg) for dikaryotic spores with nuclei in the G1 phase of the cell cycle, an indication that the spores were in G2. PMID- 8358839 TI - [History of the Baby-Friendly Hospital Initiative in Czechoslovakia]. PMID- 8358837 TI - Secretion of a Cryptococcus albidus xylanase in Pichia stipitis resulting in a xylan fermenting transformant. AB - A fragment of cDNA containing the xylanase gene (XLN) of Cryptococcus albidus was inserted into the vector pJHS which contains the selectable marker his3. To permit expression of the XLN gene, the xylose reductase promoter XYL1 from Pichia stipitis was introduced in front of the XLN gene. P. stipitis PJH53, a histidine dependent strain, transformed with this plasmid produced an active extracellular xylanase. The enzyme secreted by P. stipitis had an apparent molecular mass of 50 kDa, which was slightly greater than that of the native 48-kDa xylanase produced by C. albidus. The expression of the XLN gene in P. stipitis allowed it to use xylan as a carbon source and to ferment xylan directly to ethanol under anaerobic conditions. PMID- 8358835 TI - Molecular structure of the SWA2 gene encoding an AMY1-related alpha-amylase from Schwanniomyces occidentalis. AB - A 2.1-kb DNA fragment containing the SWA2 gene determining an alpha-amylase from Schwanniomyces occidentalis has been sequenced. It contains an open reading frame of 1521 bp which has the potential to encode a 507 amino-acid protein of M(r) 55966. Its deduced amino-acid sequence shows significant similarities to the sequence of other studied alpha-amylases. These similarities identify a consensus sequence, F(LIV)(ED)NHD, which is shared in addition by most maltases, invertases and glucoamylases. PMID- 8358840 TI - [The present status of the International Marketing Code for breast milk substitutes in Czechoslovakia]. PMID- 8358842 TI - [Immunologic properties of milk and the importance of breast feeding in neonatal immunity]. PMID- 8358841 TI - [Anatomy of the mammary gland and the physiology of breast feeding]. PMID- 8358843 TI - [The spectrum of fatty acids during lactation]. PMID- 8358844 TI - [Promotion of breast feeding 1982-1992]. PMID- 8358845 TI - [Promotion and encouragement of breast feeding in Slovakia]. PMID- 8358846 TI - [Breast feeding in southern Moravia]. PMID- 8358847 TI - [Observations by a psychologist on the situation in various maternity and neonatal departments in Prague]. PMID- 8358848 TI - Ten steps toward successful breast-feeding and the building blocks of the Baby Friendly Hospital Initiative (BFHI). PMID- 8358849 TI - Current status of the code of marketing of breastmilk substitutes. PMID- 8358850 TI - [Why the Baby-Friendly Hospital Initiative?]. PMID- 8358852 TI - Inhibition of the autoxidation of linoleic acid by phenylpropanoid glycosides from Pedicularis in micelles. AB - The activities of six phenylpropanoid glycosides as chain-breaking antioxidants have been studied for the autoxidation of linoleic acid in cetyl trimethylammonium bromide (CTAB) micelles at 37 degrees C. Verbascoside, isoverbascoside, echinacoside and pedicularioside A, which possess four phenolic hydroxyl groups, exhibited antioxidant activities, while cistanoside D possessing only two phenolic hydroxyl groups and permethyl verbascoside without phenolic hydroxyl group did not suppress the oxidation appreciably. The ratio of rate constants for inhibition and propagation kinh/kp and stoichiometric factor n were determined. PMID- 8358851 TI - Simultaneous measurements of conjugated dienes and free malondialdehyde, used as a micromethod for the evaluation of lipid peroxidation in rat hepatocyte cultures. AB - Membrane lipid peroxidation in rat hepatocyte cultures was induced by a 5-h incubation with either ethanol (50 mM) or the chelate iron-nitrilotriacetic acid (Fe-NTA) (100 microM). To test the oxidative stress, two indices were measured simultaneously on the same sample: extracellular free malondialdehyde (MDA) measured by HPLC with a size exclusion column, and conjugated dienes (CD) determined by second derivative spectroscopy. With ethanol, both CD and MDA gave nearly the same values of lipid peroxidation, about 135% of the control value. With Fe-NTA, both indices indicated a higher lipid peroxidation, but the MDA and CD values were different. Iron lipid peroxidation evaluated by free MDA and CD was, 290 and 230%, respectively, of the control. This discrepancy could be ascribed to an increased decomposition of hydroperoxides by iron. In addition, the ratio of cis,trans and trans,trans conjugated dienes, which reflects the cellular redox status, remained unchanged after 5 h of lipid peroxidation induced either by ethanol or iron. PMID- 8358853 TI - Effect of N-acylethanolamines with different acyl-chains on DPPC multilamellar liposomes. AB - The influence of N-acylethanolamines with different acyl-chains on the physico chemical state of neutral phospholipids was investigated using dipalmitoyl phosphatidylcholine (DPPC) multilamellar liposomes. The thermal dependence of steady state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and its charged derivative 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA DPH) was recorded. The N-acylethanolamines modified the DPPC phase transition temperature and broadened the transition temperature range in different ways depending on the N-acylethanolamines acyl chain characteristics. Our data suggest that the N-acylethanolamine acyl chain length and unsaturation play an important role in the interaction of these compounds with model membranes. The results show that long-chain-N-acylethanolamines interact largely with DPPC model membranes while a similar effect is not observed for the short ones. PMID- 8358854 TI - Chromatographic and mass spectrometric characterization of 3-O-benzoyl methyl ester derivatives of mycolic acid fractions from Corynebacterium pseudotuberculosis, C. diphtheriae and Rhodococcus rhodochrous. AB - A benzoyl group was attached to the 3-hydroxyl group of the methyl ester derivative of corynomycolic acid fraction isolated from Corynebacterium pseudotuberculosis. The infrared spectrum of the 3-O-benzoylated compound displayed a series of characteristic absorptions found at 1110, 1267 and 1603 cm 1 that confirmed the presence of a monosubstituted phenyl grouping. The 1H-NMR spectrum showed peaks representing protons of the aromatic ring at 7.4 ppm and 8.0 ppm. The UV spectrum revealed two absorption maxima: at 190 and 228 nm. The mass spectrum of the 3-O-benzoylated material exhibited the following peaks: (1) a prominent peak at m/z 105 of the benzoyl group that constituted the base peak; (2) peaks of methyl esters representing the alpha-hydrocarbon side chain plus carbon atoms C1 and C2 of the mycolic acid molecule; and (3) peaks of molecular ion minus benzoic acid and/or molecular ion minus benzoxyl group. When subjected to liquid chromatography (LC) on an octadecylsilane-silica gel column the 3-O benzoylated methyl ester derivatives of the corynomycolic acid fraction were separated into their constituent homologous fractions corresponding to underivatized corynomycolic acids with the chain length C30, C32 and C34. Reversed phase HPLC of saturated and monounsaturated species of 3-O-benzoylated derivatives of the mycolic acid fraction from C. diphtheriae and Rhodococcus rhodochrous led to the separation of the corresponding homologous fractions. Mass spectrometry by electron impact mode identified both series of the homologous materials differing in mass by 28 units. PMID- 8358855 TI - The role of T cells in myosin-induced autoimmune myocarditis. PMID- 8358856 TI - T cells in cardiac myosin-induced myocarditis. AB - Autoimmune myocarditis induced by immunization with cardiac myosin can be seen as a virus-free system to analyze the immunopathological mechanisms of certain forms of postinfectious heart disease. Immunodepletion studies have shown that in A.SW mice myosin-induced myocarditis is mediated by both CD4+ and CD8+ cells. The CD4+ subset is at least required for the induction of the autoimmune response, whereas the CD8+ subset seems to play a key role in mediating the myocardial injury. In addition, we found a bias concerning the TCR repertoire, because T cells within the inflammatory heart infiltrate almost exclusively use V beta 8 elements. Furthermore, recent serologic and immunohistologic studies indirectly suggest that the cardiac myocyte is not the target for the anti-myosin response. Rather, the primary target might consist in dendritic cells presenting myosin epitopes even under normal conditions. PMID- 8358857 TI - Interstitial connective tissue matrix alterations in acute murine Chagas' disease. PMID- 8358858 TI - A clinicopathologic description of myocarditis. PMID- 8358859 TI - Vascular HLA-DR expression correlates with pathologic changes suggestive of ischemia in idiopathic dilated cardiomyopathy. PMID- 8358860 TI - Immunologic dialogue between cardiac myocytes, endothelial cells, and mononuclear cells. PMID- 8358861 TI - Mechanisms of action of cyclosporine: considerations for the treatment of autoimmune diseases. PMID- 8358863 TI - Modulation of mouse preimplantation development by epidermal growth factor receptor antibodies, antisense RNA, and deoxyoligonucleotides. AB - Two-cell mouse preimplantation embryos were cultured for 48 h in four different reagents to modulate epidermal growth factor (EGF) receptor function. These were rabbit polyclonal and mouse monoclonal antibodies to EGF receptor, EGF receptor antisense RNA, and EGF receptor antisense deoxyoligonucleotides. Embryos were scored for two endpoints: onset of cavitation as a measure of trophectoderm differentiation and mean embryo cell number as a measure of cell proliferation. The consistent observations were that cavitation was significantly accelerated by antibodies and delayed by antisense RNA and antisense deoxyoligonucleotides. None of these reagents exerted a significant effect on mean embryo cell number, with one exception, the polyclonal antibody. Our interpretation of these observations is that the antibody binding facilitated cavitation by mimicking natural ligand receptor binding and inducing the signal transduction cascade that is typical for the EGF receptor. In the case of antisense RNA or deoxyoligonucleotide, we propose that they delayed onset of cavitation by interfering with EGF receptor production. We hypothesize that during this period of development, EGF receptor is concerned predominantly with the regulation of differentiation more than with cell proliferation. PMID- 8358862 TI - Immunopathogenesis of HIV-1-associated cardiomyopathy. PMID- 8358864 TI - The Xenopus platelet-derived growth factor alpha receptor: cDNA cloning and demonstration that mesoderm induction establishes the lineage-specific pattern of ligand and receptor gene expression. AB - We have cloned the Xenopus PDGF alpha receptor cDNA and have used this clone, along with cDNA encoding PDGF A, to examine their expression pattern in Xenopus embryos and to determine the factors responsible for lineage specificity. Recombinant Xenopus alpha receptor expressed in COS cells exhibits PDGF-A dependent tyrosine kinase activity. We find that receptor mRNA is present in cultured marginal zone tissue explants and in animal cap tissue induced to form mesoderm either by grafting to vegetal tissue or by treatment with recombinant activin A. In contrast, PDGF A mRNA is expressed in cultured, untreated animal cap tissue and is suppressed by mesoderm induction. These results suggest that ectodermally produced PDGF A may act on the mesoderm during gastrulation and that mesoderm induction establishes the tissue pattern of ligand and receptor expression. PMID- 8358865 TI - Possible autocrine/paracrine actions of insulin-like growth factors during embryonic development: expression and action of IGFs in undifferentiated P19 cells. AB - The insulin-like growth factors I and II (IGF I and II) and their cell surface receptors are expressed in the mammalian embryo and may function as autocrine or paracrine growth factors during early development. P19 embryonic carcinoma cells, derived from a 7.5 day mouse embryo, were used as a model for a functional study of the IGF system in post-implantation embryogenesis. Undifferentiated P19 cells synthesized IGF I and II, the type I and II IGF receptors, and IGF binding proteins (IGF BP2, IGF BP3, and IGF BP4). P19 cells showed an increase in thymidine incorporation of 150% of control with a 4 hour incubation of IGF I (10 ng/ml) or IGF II (100 ng/ml) and an increase in cell viability compared to control cells during 24 hours of serum starvation. In both experiments IGF I was more potent than IGF II. Endogenous concentrations of IGF I and II in conditioned media were low compared to the doses of exogenous IGFs required for biologic effect, but nonetheless contributed significantly to baseline DNA synthesis, as demonstrated by inhibition of IGF actions with specific antibodies. Cell surface associated IGF BPs bound more radiolabeled IGF than IGF receptors, as determined by binding studies and affinity cross-linking. IGF I and IGF II appeared to regulate production of IGF BP2, suggesting that the IGFs may regulate their own actions by altering the abundance of their binding proteins. PMID- 8358866 TI - Transforming growth factor-beta in the early mouse embryo: implications for the regulation of muscle formation and implantation. AB - In a search for functions of transforming growth factor-beta during early embryonic development we used two different experimental approaches. In the first we made use of embryonic stem (ES) cells. ES cells in culture differentiate to derivatives of all three germ layers and mimic some aspects of organogenesis when grown as aggregates in suspension to form embryoid bodies. Differentiation proceeds further when the embryoid bodies attach to suitable substrates. Muscle and neuronal cells are among the most readily identified cell types then formed. We examined the effect of all-trans retinoic acid (RA) and members of the transforming growth factor-beta family (TGF-beta 1, TGF-beta 2) under these conditions in an assay where single aggregates formed in hanging microdrops in medium supplemented with serum depleted of lipophilic substances which would include retinoids. Endoderm-like cells formed under all conditions tested. RA at concentrations of 10(-8) M and 10(-7) M induced the formation of neurons but in the absence of RA or at concentrations up to 10(-9) M, neurons were not observed. Instead, beating muscle formed in about one-third of the plated aggregates; this was greatly reduced when RA concentrations increased above 10(-9) M. Immunofluorescent staining for muscle specific myosin showed that two muscle cell types could be distinguished: elongated, non-contractile myoblasts and mononucleate flat cells. The mononucleate flat cells appeared to correspond with rhythmically contracting muscle. The number of non-contractile myoblasts increased 3-fold over controls in the presence of 10(-9) M RA. TGF-beta s increased the number of contractile and non-contractile muscle cells by a factor 3 to 7 over controls, depending on the TGF-beta isoform added and the muscle cell type formed. TGF-beta 2 also invariably increased the rate at which contracting muscle cells were first observed in replated aggregates. The stimulatory effect of TGF-beta s on the formation of mononucleate flat cells was completely abrogated by RA at 10(-9) M while the number of myoblasts under similar conditions was unchanged. These data suggest that a complex interplay between retinoids and TGF-beta isoforms may be involved in regulation of differentiation in early myogenesis. In the second approach, neutralizing polyclonal rabbit antibodies specific for TGF-beta 2 were injected into the cavity of mouse blastocysts 3.5 days post coitum (pc). After 1 day in culture, embryos were transferred to pseudopregnant females. The number of decidua, embryos and resorptions were counted at day 8.5-9.5 pc.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8358867 TI - Rapid induction and clearance of TGF beta 1 is an early response to wounding in the mouse embryo. AB - The TGF beta family of growth factors has been implicated as playing a significant role in many aspects of embryonic morphogenesis, and also as a mediator of adult tissue repair processes. Unlike the situation in the adult, tissue repair in the embryo does not result in scarring, and it has been suggested that this might be due, in part, to reduced levels of growth factors, particularly TGF beta, at the wound site. We have examined the expression patterns of TGF beta genes following wounding of limb bud lesions in cultured E11.5 mouse embryos. The timetable of wound closure was investigated by standard light and electron microscopy from the time of wounding until the lesion had re epithelialised 24 hours later. The expression of transcripts for each of the three TGF beta genes was examined at various time points during the healing process using radioactive in situ hybridisation to tissue sections and wholemount non-radioactive in situ hybridisation to embryo pieces. Within 1 to 3 hours of wounding, transcripts encoding TGF beta 1 were rapidly induced within the epithelial cells of the wound margin, particularly those cells at the ventral aspect of the wound. By 3 to 6 hours post-wounding, TGF beta 1 transcripts were detectable in the mesenchyme of the wound bed. No TGF beta 3 induction was observed, and possible TGF beta 2 induction was largely obscured by endogenous expression associated with pre-cartilage mesenchymal condensation. Immunocytochemical analysis of tissue sections of the wound demonstrated a rapid induction of TGF beta 1 protein within 1 hour post-wounding, but also a subsequent rapid clearance of the protein from the wound site such that, by 18 hours post-wounding, TGF beta 1 levels had returned to near background. These data are discussed in terms of the molecular mechanisms underlying embryonic wound healing and the significance of the results to an understanding of scarring following adult tissue repair. PMID- 8358868 TI - Site of action of imprinted genes revealed by phenotypic analysis of parthenogenetic embryos. AB - The phenotypes of early post-implantation parthenogenetic embryos were examined. The spectrum of phenotypes suggested that three stages are adversely affected by imprinting--implantation, pregastrulation, and postgastrulation. Survival of parthenogenetic embryos past these developmental blocks can be improved but not completely overcome by experimental asynchrony. These results suggest that imprinting may be "leaky" at early stages. PMID- 8358869 TI - Focal segmental glomerulosclerosis (FSG) 20 years later. From toddler to grown up. AB - In 1981, we reported the outcome of 25 children with FSG after a follow-up of 10 years. In 1991, all the living patients were reevaluated. Ten patients are now in sustained remission. Four patients still present heavy proteinuria with a normal glomerular filtration rate, four required dialysis and seven patients have died. The renal survival curve has stabilized at 56%. These data show an overall outcome slightly more favourable than we had initially reported in 1981. The difference probably stems from our referral system which enables us to see the patients at an earlier stage of their disease. The percentage of deaths is important. Among the various clinical or histological factors of predictive prognostic value only the degree of interstitial damage has reached statistical significance (p < 0.02). PMID- 8358870 TI - Urinary levels of IL-6 in patients with active lupus nephritis. AB - Using the IL-6 dependent hybridoma, MH60.BSF2, we measured urinary levels of interleukin 6 (IL-6) in 29 patients with active lupus nephritis. We detected IL-6 activity in the urine of 24 (83%) of 29 patients before the initiation of therapy. The median value of urinary IL-6 levels in patients with a histologic diagnosis of WHO class IV on renal biopsy was significantly higher than that in patients with other classes (p < 0.01). After treatment, urinary levels of IL-6 decreased significantly (p < 0.001). These data suggest that urinary levels of IL 6 may be a valuable tool for monitoring the progression of lupus nephritis. PMID- 8358871 TI - An association between ANCA positive renal disease and malignancy. AB - The detection of anti-neutrophil cytoplasmic antibodies (ANCA) is now a routine part of the evaluation of patients clinically suspected of suffering from small vessel vasculitis. The factor(s) that trigger the development of these autoantibodies and their role in the pathogenesis of vasculitis is still unclear. We describe four patients who presented to us since June 1990. All patients had positive ANCA serology and had clinical evidence of vasculitis. In all patients soon after the establishment of ANCA positivity, a carcinoma of either the respiratory or urinary tracts was diagnosed. We suggest that in some cases of ANCA-associated vasculitis, malignant disease may be a trigger for either the generation of these autoantibodies, or the development of vasculitis. PMID- 8358872 TI - Tubular proteinuria in steroid sensitive multi-relapsing nephrotic syndrome. AB - The urinary excretion of N-acetyl-beta-D-glucosaminidase (UNAG) and retinol binding protein (URBP) was studied in 65 children with steroid sensitive multirelapsing nephrotic syndrome (MRNS): 28 on cyclosporin A (CyA) therapy, 22 on prednisolone (P), 15 off-treatment and in 32 normal children to assess renal tubular damage or dysfunction. The urinary protein excretion was expressed in relation to that of creatinine (UNAG/UC in mumol pnp/h/mmol; URBP/UC in microgram/mmol). There was a weak but significantly negative correlation between age and both, UNAG/UC (r = -0.38, p < 0.01) and URBP/UC (r = -0.50, p < 0.05) in normal children, but not in nephrotics. In normals and in patients off steroids an association between these two proteins was found (r = 0.38, p < 0.05; r = 0.56, p < 0.05 respectively). Geometric mean UNAG/UC was significantly higher in nephrotics on CyA therapy (26.5 +/- 4.0), and on P (37.0 +/- 7.9) as well as in those off-treatment (16.3 +/- 3.1) compared to normal children (9.3 +/- 3.4). There was a further increase in those with raised urinary albumin: creatinine ratio (UA/UC) (> 0.1 mg/mg). URBP/UC was not increased in any of the groups of children with MRNS. Raised NAG in urine may therefore indicate active nephrotic syndrome rather than being due to the drug therapy. PMID- 8358873 TI - Effect of age and gender on kidney function in renal transplant donors: a prospective study. AB - We evaluated the long-term residual renal function in 64 living related kidney donors. Our main objective was to identify baseline factors, including gender and age, that could predict renal impairment after nephrectomy. Forty-four (69%) of the 64 donors were women. The mean +/- SEM age of those studied was 36 +/- 1.3 years and their mean +/- SEM duration of follow-up was 62 +/- 4.9 months (range, 6 to 174). Overall mean serum creatinine concentration after kidney donation was increased compared to baseline values (1.13 mg/dl vs 0.92 mg/dl, respectively, p < 0.001). At the last follow-up visit, post-nephrectomy mean glomerular filtration rate (GFR) values, adjusted for body surface area, age at donation, baseline serum creatinine and duration of follow-up, measured by 99mTc-DTPA were significantly lower in women than in men (72.11 ml/min vs 87.17 ml/min, respectively, p = 0.02). At follow-up, mean effective renal plasma flow, adjusted for the same variables, measured by 131I-hippuran was also significantly lower in women compared to men (318.07 ml/min vs 400.82 ml/min, respectively, p < 0.01). Eleven of twelve patients with post-nephrectomy GFR values less than 60 ml/min were women. Following nephrectomy, serum creatinine concentration increased significantly as a function of greater age at donation in women but not in men. Similarly, in women but not in men, follow-up GFR measurements decreased significantly as a function of age after adjusting for baseline serum creatinine and duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358874 TI - Clinical significance of vesicoureteral reflux after kidney transplantation. AB - In this study 103 out of our 125 CsA-treated patients who received between January 1985 and December 1989 a first cadaver kidney transplant that functioned for at least one year were studied with voiding cystography (VC) for vesicoureteral reflux (VUR). All patients had an external uretero-neo-cystostomy. VUR occurred in 89 (86.4%) patients. Patients were grouped according to VUR: absence of VUR (group 0), VUR grade I-II (group 1-2), and VUR grade III (group 3). The 3 groups were comparable for male/female ratio, cause of renal failure, cause of donor death, recipient and dialytic age, immunosuppressive therapy, follow-up, time of VC performance after transplantation. At 6 months and 1, 2, 3, 4, and 5 years after transplantation graft function, number of rejection episodes, and number of urinary tract infections (UTIs) were similar in the 3 groups. In groups 1-2 and 3 hypertension was more frequent than in group 0 and occurred even after the 6th month (whereas this did not happen in group 0), but the differences between the 3 groups were not significant. However, when only the 13 patients who were followed for 5 years were considered, the prevalence of hypertension after 5 years was significantly higher in groups 1-2 and 3 (both 100.0%) than in group 0 (33.3%) (chi-square = 7.88; p < 0.02). Finally, 4.5% of patients with VUR and no patients without VUR had septic episodes linked to UTIs, but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358875 TI - Plasticizers induced mononuclear cells interleukin 1 production: implications with peritoneal sclerosis. PMID- 8358876 TI - Central venous hemodialysis catheter related superior vena cava syndrome. PMID- 8358877 TI - Effects of indomethacin misoprostol on GFR. PMID- 8358878 TI - Heart failure: drug therapy in the nineties and beyond. AB - The lesson learned from recent advances in the understanding of congestive heart failure is that it is too complex a process to be managed in a simple fashion. At present, incremental improvement such as that provided by ACE inhibitors, and now possibly by new agents such as flosequinan, are what we have to offer our patients, short of transplantation, to control symptoms and increase exercise tolerance. No one knows what the future holds for these patients, but one can hope that the current therapy and those drugs being studied in clinical trials will provide agents that will continue to reduce the morbidity and mortality associated with current therapies. However, only so much can be done with drugs in the failing heart, and research must continue in the area of cardiac transplantation as well as in the area of totally implantable ventricular assist devices. PMID- 8358879 TI - Sarcoidosis of the heart. AB - Myocardial involvement in sarcoidosis occurs in about 27% of patients. Clinical manifestations include ventricular arrhythmias, conduction abnormalities, and sudden death. Diagnosis requires clinical suspicion and may be supported by electrocardiography, echocardiography, thallium imaging, gallium-67 scanning, and myocardial biopsy. Steroids seem to be beneficial in the treatment of myocardial sarcoidosis. Those who do not respond to medical treatment may benefit from cardiac transplantation. PMID- 8358880 TI - Low-dose dobutamine stress test for the evaluation of cardiac function using ultrafast computed tomography. AB - High dose-dobutamine (DOB) has been previously used as a pharmacological stress test to evaluate wall motion abnormalities. As a result, recent stress echocardiography with low-dose DOB has been reported to be valuable for investigating stunned myocardium after thrombolysis. However, echocardiography requires an operator's skill and experience to evaluate wall motion abnormalities which are subjectively determined by the observer. In contrast, ultrafast computed tomography (UFCT) does not necessarily require extreme technical skill and experience. To evaluate the feasibility of stress UFCT with low-dose DOB, we scanned 10 normal subjects along the short-axis by 8-slice-multicine mode. After scanning at rest for baseline, we scanned during the administration of 4 and 8 micrograms/kg/min of DOB, respectively, for 5 min. Ejection fraction, contraction, and thickening were higher during 8 micrograms/kg/min of DOB than during 4 micrograms/kg/min of DOB and baseline, while the above values were higher during 4 micrograms/kg/min of DOB than during baseline (p < 0.01). It was possible to detect changes of cardiac function and wall motion due to low-dose DOB by UFCT. We therefore conclude that UFCT is a reliable modality for evaluating cardiac function and wall motion for low-dose DOB stress test because of its excellent spatial and contrast resolution. PMID- 8358881 TI - Exertional hemodynamics in women with chest pain--an aortic Doppler ultrasound study. AB - Aortic ultrasound Doppler recordings of stroke volume, maximal flow velocity, and acceleration can be used to assess central hemodynamic effects of exercise in coronary artery disease (CAD) and left ventricular dysfunction. We wanted to evaluate the time course and amplitude of changes in aortic Doppler ultrasound parameters in women during supine exercise and the potential diagnostic value of a submaximal supine exercise test. For this purpose, 18 women who had undergone coronary angiography because of incapacitating chest pain (10 with significant coronary stenoses and previous myocardial infarction, 8 without stenoses or infarction) were compared with 10 healthy controls. Pathological electrocardiographic (ECG) ST-segment depression during supine exercise was common in all groups. In the control group, a significant increase of stroke volume (10%), maximal aortic flow velocity (27%), and acceleration (43%) occurred at low load during exercise. Women with CAD showed no increase and a lower cardiac output during exercise, indicating left ventricular dysfunction. Women with syndrome X resembled the controls but had a higher maximal flow velocity at rest, which may indicate hyperdynamic circulation. We conclude that a test up to 40% of seated maximal load is valuable and often sufficient when assessing the hemodynamic effects of supine exercise by Doppler ultrasound in terms of stroke volume, maximal flow velocity, and acceleration. By characterizing left ventricular function in groups of female patients where false-positive stress ECG reactions are common, Doppler ultrasound may contribute to the understanding and clinical management of women with chest pain. PMID- 8358883 TI - Ventricular arrhythmias late after myocardial infarction are related to hypomagnesemia and magnesium loss: preliminary trial of corrective therapy. AB - It has been well established that in acute myocardial infarction (MI) many patients display low serum magnesium (Mg). This is associated with complex ventricular arrhythmias. The question arises whether predischarge arrhythmias occurring late after MI might also be related to Mg imbalance. In 118 patients subjected to heart rhythm 24 h Holter monitoring in the second or third week after MI, we investigated (1) the relationship between serum Mg, urinary Mg loss, and ventricular arrhythmias, and (2) the effect of Mg supplementation on heart rhythm disturbances. In patients with undisturbed rhythm or monomorphic ventricular ectopic beats (VEB) (Lown 0-2; n = 84), mean serum Mg level (mg% +/- SD) was 1.83 +/- 0.21, whereas in patients with multifocal VEB, pairs, or nonsustained ventricular tachycardia (VT) (Lown 3-4; n = 34) serum Mg was decreased to 1.68 +/- 0.27 (p < 0.01). Serum Mg normal range in our laboratory is 1.7-2.6 mg%. The lowest serum Mg reaching 1.55 +/- 0.27 was found in nonsustained VT (Lown 4 b) subgroup (n = 14). Urinary Mg loss measured in 81 patients was more pronounced in those with Lown 3-4 arrhythmias (n = 26) than with Lown 0-2 (n = 55). The daily values were 73 +/- 22 and 54.4 +/- 26 mg, respectively (p < 0.001). Thirteen patients with complex arrhythmias and low serum Mg received Mg supplementation (MgSO4, 8 g in 500 ml 5% glucose intravenously during 24 h). This resulted in restoration of almost undisturbed rhythm in 10 subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358882 TI - Safety of transvenous right ventricular endomyocardial biopsy guided by two dimensional echocardiography. AB - A total of 231 endomyocardial biopsy procedures performed in 74 consecutive patients were evaluated to compare the incidence and nature of complications in procedures guided by fluoroscopy versus those guided by echocardiography. Sixty biopsy procedures were guided by fluoroscopy and 171 by two-dimensional echocardiography. The right interventricular septum was the target site for biopsy sampling in all patients. Clinical signs of myocardial perforation occurred during one (1.7%) procedure guided by fluoroscopy versus two (1.2%) procedures guided by echocardiography. Two cases of interventricular septal perforation were visualized during the echo-guided procedures. The biopsy specimens were judged to be inadequate for diagnosis in 2.2% of the biopsy procedures, all of which were guided by fluoroscopy. The number of samples obtained during a procedure guided by fluoroscopy was lower (mean 2.3 +/- 1.6) (mean +/- 1 SD) than that taken during a procedure guided by echocardiography (mean 4.0 +/- 1.2). Epicardial or pericardial tissue was present in 5.8% of the samples obtained under fluoroscopic guidance, versus 0.7% of the samples obtained using echocardiography (p = 0.0003). It is concluded that although echocardiography seems to provide more accurate and safer guidance for the positioning of the bioptome toward the septum, the presence of epicardium or pericardium in 0.7% of the samples indicates that inadvertent sampling from the right ventricular free wall cannot be avoided. PMID- 8358884 TI - Determinants of immediate and follow-up results of pulmonary balloon valvuloplasty. AB - The data of 93 patients (age 11.4 +/- 9.4 years, range 8 months-56 years) who underwent pulmonary balloon valvuloplasty (PBV) for valvular pulmonic stenosis (PS) in our institution are reviewed. The patients were classified into three groups: Group I (34 patients) had a right ventricular (RV) to aortic systolic pressure ratio of < 1, Group II (39 patients) had suprasystemic RV systolic pressures, and Group III (20 patients) included patients with elevated mean right atrial (RA) pressures irrespective of the RV systolic pressures. The percentage drop in immediate postdilatation peak systolic gradients (PSG) and the follow-up PSG were similar in the three groups and were not influenced by any predilatation patient characteristics. A balloon-annulus ratio < 1 predicted a poorer follow-up outcome. Nine patients, eight of Group III and one of Group II, experienced difficult procedures requiring sequential use of progressively larger balloon catheters. Eleven patients, six of Group II and five of Group III, experienced procedure-related events (hypotension, bradycardia/asystole, hypoxia, apnea, tachyarrhythmias, and seizures) and one patient (Group II) died. Although changes in immediate and follow-up gradients after PBV are not influenced by the severity of PS, difficult procedures and procedure-related events are particularly common in patients with severe PS and elevated RA pressures. A cautious and planned approach is therefore indicated in these patients. PMID- 8358885 TI - Lone atrial fibrillation and anticoagulant therapy. AB - Assessment of risk of thromboembolism and potential benefit of prophylaxis with long-term anticoagulant therapy in lone atrial fibrillation is hampered by a lack of consensus regarding definition of lone atrial fibrillation. In general, patients less than 60 years of age with normal left ventricular function and left atrial size have a low risk of thromboembolic events and are unlikely to gain any significant benefit with anticoagulants; however, patients older than 60 years with impaired left ventricular function, enlarged left atrium, and/or associated conditions such as hypertension have an increased risk of thromboembolism and would benefit from long-term anticoagulant therapy. Decisions regarding anticoagulant usage would be simplified by using a scoring system containing clinical and investigational variables. PMID- 8358886 TI - Anatomy, histology, and pathology of the cardiac conduction system--Part IV. AB - Metastatic tumor involvement of the heart as a basis for the genesis of various cardiac arrhythmias is reviewed. The morphologic basis of pre-excitation syndromes and right ventricular dysplasia are also reviewed. PMID- 8358887 TI - Hypothyroid cardiac tamponade presenting with severe systemic hypertension. AB - Hemodynamic data are presented which not only depict typical tamponade physiology, but demonstrate that hypotension may not necessarily be present with slow accumulation of pericardial fluid in myxedema patients. This case is unique in that severe hypertension, as part of the presentation of hypothyroid tamponade, has never been reported. PMID- 8358888 TI - Stress-induced polymorphous ventricular tachyarrhythmias in two brothers: unusual pattern of inheritance in the long QT syndrome. AB - Two brothers, 10 and 9 years old, are reported who were treated for years with antiepileptic drugs until the cardiac origin of their syncopal attacks was discovered. Our findings are consistent with the diagnosis of long QT syndrome, although no other family members are affected and only intermittent and mostly borderline QT prolongation could be found. Diagnostic difficulties and genetic implications are discussed. PMID- 8358889 TI - Harold Nathan Segall (1897-1990). PMID- 8358890 TI - The differential effects of FSH and LH on the human ovary. AB - The basic foundation for normal puberty and adult reproductive function is established during fetal life with the adequate development of the hypothalamus, pituitary and gonads. Further maturation and differentiation of the hypothalamic pituitary-gonadal axis continues throughout childhood, puberty, adult life and senescence. Pituitary FSH and LH play a central role in the cascade of events in the hypothalamic-pituitary-gonadal axis by mediating between the brain and hypothalamus on one hand and the end-organ, the ovary, on the other. Absent or low pituitary secretion of FSH and LH, as occurs in hypothalamic/pituitary hypogonadism, leads in women to anovulation, amenorrhoea and absent ovarian follicular development. The ability of gonadotrophins to modulate ovarian function depends on their rate of synthesis by the pituitary gonadotrophs, on their circulating concentrations (which vary throughout life and throughout the menstrual cycle), on the relative abundance of the multiple forms of gonadotrophins that have varying biological activity, on the presence of their receptors on the different cell types of the ovary, on the intracellular adenylate cyclase enzyme that causes the production of cAMP, and on the extra- and intragonadal factors that are able to modulate the effects of gonadotrophins in the ovary. Recent clinical and basic research with recombinant gonadotrophins, molecular biological studies on the localization, function and regulation of the long sought after gonadotrophin receptors, as well as research on the interaction between gonadotrophins and local intragonadal factors have widened our knowledge about the function and role of FSH and LH in the ovary and have provided new insights into previously unanswered questions of ovarian physiology and pathophysiology and will provide the basis for the design of new treatment strategies to overcome ovulatory gonadotrophin-dependent dysfunction in the future. PMID- 8358891 TI - The significance of elevated FSH for reproductive function. AB - 1. Women aged 40 or more with favourable hormone profiles can do well in assisted reproduction, while women of any age with basal FSH levels greater than 20 IU/litre will be poor responders to ovarian stimulation. 2. Basal FSH is an important predictor of ovarian reserve--levels over 25 IU/litre are rarely associated with ongoing pregnancy, and the best chance for pregnancy is an FSH between 10 and 20 IU/litre. 3. A basal E2 over about 50 pg/ml predicts poor ovarian reserve. 4. Age remains an important factor even when the FSH and E2 levels are known. 5. Optimal prediction involves simultaneous consideration of age, FSH, LH and E2. 6. Provocative tests of ovarian reserve are probably superior but are not as simple as static tests. 7. Defined risks of multiple pregnancy can be controlled by adjusting the number of pre-embryos transferred according to age and FSH levels. 8. Cases of otherwise unexplained infertility may be uncovered by evaluating basal FSH and E2 levels. PMID- 8358892 TI - The FSH threshold concept in clinical ovulation induction. PMID- 8358893 TI - The step-down principle in gonadotrophin treatment and the role of GnRH analogues. AB - This chapter has focused on the step-down principle for gonadotrophin induction of ovulation in women suffering from clomiphene-resistant anovulation. The physiological rationale of this approach has been highlighted. Under normal conditions, FHS levels surpassing the FSH threshold initiate gonadotrophin dependent growth of a cohort of follicles (this process is referred to as 'recruitment'). Due to negative feedback actions, the FSH levels decrease and FSH is above the threshold for only a limited number of days (the 'FSH window'). Around the mid-follicular phase, selection of a dominant follicle takes place; in addition to relatively low serum FSH concentrations, intraovarian regulation appears to be important for this process. In the conventional step-up or low dose step-up protocols for gonadotrophin induction of ovulation, administered doses are kept constant once an 'adequate' ovarian response is observed, resulting in high FSH serum levels in the late follicular phase and a broad FSH window. This contradicts normal circumstances and may give rise to unintended interference with the selection process by continuously stimulating follicles to enter the growing pool. This may result in multiple follicle development which, in turn, may be related to higher rates of multiple pregnancies and ovarian hyperstimulation. Potential mechanisms underlying arrested follicle maturation in PCOS are also discussed since they appear to be of relevance for the induction of ovulation. Disturbed selection can be overcome in the majority of cases by elevating the serum FSH concentrations through the administration of exogenous gonadotrophins to surpass the elevated FSH threshold in these patients. Data obtained by our group so far suggest that in PCOS patients treated with gonadotrophins in a step-down fashion, follicles continue to mature and can be stimulated to ovulation. Moreover, the number of functionally active medium-sized follicles seems to be reduced. If monofollicular development is observed in these patients, growth rates and oestrogen serum levels are indistinguishable from unstimulated normal development of the dominant follicle. In our initial series of over 200 cycles of gonadotrophin treatment according to the step-down principle in clomiphene-resistant anovulatory patients, 84% of cycles were ovulatory and pregnancy was achieved in 18% of the cycles (giving a cumulative pregnancy rate of 51%). Moreover, the overall complication rate appears to be low. The potential advantages and critical points of adjuvant treatment with GnRH analogues is also discussed. It has been clearly demonstrated that premature luteinization can be prevented effectively. Various other potential advantages of cotreatment seems to justify adjuvant medication with GnRH agonists.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8358894 TI - Clomiphene citrate: the case for a monoisomeric preparation. PMID- 8358895 TI - Ovulation induction in gonadotrophin-resistant women. AB - The patient who has gonadotrophin-resistant ovaries and who requires ovulation induction or superovulation for IVF presents a serious problem. The diagnosis is usually made in the first treatment cycle which is either abandoned due to a failure of response, requires inordinately high doses of gonadotrophins to induce a response or fails to induce satisfactory oestradiol levels and/or follicular development. This situation is often associated with advanced maternal age and high day 3 concentrations of FSH. The possible treatment strategies that we have described seem to offer only a partial solution to specific subgroups of poor responders. These include protocols of clomiphene/hMG, mini-dose GnRH agonist regimens, and cotreatment with GH, each of which may be found to be effective in individual cases. Taking into account today's increasing demand for pregnancy in older aged women, more research is needed to evolve more efficient solutions for this difficult problem. PMID- 8358896 TI - The luteinized unruptured follicle syndrome. PMID- 8358897 TI - Ovulation induction for luteal phase defects and luteal phase defects after ovulation induction. PMID- 8358898 TI - Surgical options in polycystic ovary syndrome patients who do not respond to medical ovulation induction. AB - Women with PCOS often present with anovulatory infertility. In these women, attempts at ovulation induction should be initiated with clomiphene citrate. However, 10 to 15% of women will not ovulate in response to clomiphene citrate, and in those who do, half will not conceive. Ovulation induction in these patients may involve the administration of hMG or pure FSH, with or without prior pituitary desensitization by GnRH agonists. However, gonadotrophin therapy is expensive, requires extensive monitoring, is not available at all centres and is associated with a significant incidence of ovarian hyperstimulation syndrome, multiple pregnancy and pregnancy loss. Furthermore, the chance of conception is limited to the treatment cycle. For women who fail to respond to clomiphene citrate therapy, and for whom gonadotrophin therapy is unsuccessful or unavailable, surgical therapy should be considered. There is a very limited role, if any, for OWR in the treatment of anovulation due to PCOS. Although effective in inducing ovulation in approximately 80% of women, with pregnancy rates approximating 60%, OWR requires major surgery and is associated with significant adhesion formation. Newer, less invasive techniques are emerging for the anovulatory woman who fails medical management. These include laparoscopic ovarian cautery and laparoscopic ovarian laser vaporization. These surgical techniques can be performed as outpatient procedures and may be combined with a diagnostic laparoscopy. Knowledge of the long-term effects of these techniques is still limited, but results appear promising, with spontaneous ovulation being initiated in 70 to 90% of women. Of the patients who remain anovulatory or oligo ovulatory after these procedures, most will have been rendered sensitive to clomiphene citrate. Conception rates approximate 60%. The mechanism of action remains uncertain, but is likely to involve alteration of the intraovarian steroid environment and, in turn, the feedback to the hypothalamic-pituitary axis. The overall result is normalization of gonadotrophin drive and follicular microenvironment, allowing follicular recruitment and development to proceed to ovulation. Future clinical studies with long-term follow-up will be required to determine relapse rate and fecundity rates following these procedures. The risk of postoperative adhesion formation and the role of second-look laparoscopy in the prevention of this undesirable complication remains uncertain. Until more complete, long-term information is known, caution must be exercised and complete information provided to the patient with respect to the possible adverse affects. PMID- 8358899 TI - Complications of ovulation induction. AB - Induction of ovulation has its own risks. Since this treatment is elective the physician should be convinced that it is really indicated for the specific patient. Multiple pregnancies still occur in 4 to 15% in in vivo treatment and in 15 to 20% in assisted reproduction. Abortions occur in 20% of the pregnancies achieved. These numbers demonstrate the complexity of induction of ovulation. In recent years the average age of the treated patient has increased, but it is too early to see whether this influences the frequency of complications. The physician should be aware of the possible complications and should remain in contact with the patients at risk after completion of the treatment. The patient should be well informed about the possible complications before starting treatment. At the end of the treatment she should be able to recognize any clinical warning signs of OHSS and inform her physician, in order to be treated appropriately. Further studies of the pathogenesis of OHSS in the future will hopefully lead to more specific treatments or even prevention of this phenomenon. The increasing experience in selective fetal reduction seems to be a practical solution to high rank multifetal gestation, preventing extreme prematurity and its sequelae. PMID- 8358900 TI - Ovulation, ovulation induction and ovarian carcinoma. PMID- 8358901 TI - Results of nonoperative management of full-thickness tears of the rotator cuff. AB - The results of nonoperative management of 53 patients with full-thickness tears of the rotator cuff proven by arthroscopic examination was as follows. Patients were treated with nonsteroidal antiinflammatory medication, stretching, strengthening, and occasional steroid injections. Average age at presentation was 62.2 years. Patients were evaluated at an average of 7.6 years. Forty patients were male, and the dominant limb was involved in 40 cases. Thirty-four patients were reviewed by questionnaire and physical examination, whereas 19 patients were evaluated by telephone interview only. In 40 patients, the onset of symptoms was associated with an injury. In 12 patients, workmen's compensation was involved. At follow-up evaluation, the 34 shoulders that were available for examination were evaluated for pain, range of motion, strength, and function. Thirty-nine of the 53 patients (74%) assessed subjectively had only slight or no shoulder discomfort. Of the 28 shoulders presenting within three months of injury, 24 (86%) were rated as satisfactory at the time of latest evaluation. Of the 16 patients who initially had had shoulder pain for over 6 months, only nine (56%) were rated as satisfactory. Most patients showed improvement with regard to their ability to perform activities of daily living. Average active total elevation was 149 degrees compared with 121 degrees at initial presentation. Thirty-two of the 34 patients examined (94%) had evidence of weakness on muscle testing and 19 (56%) had demonstrable muscle atrophy. PMID- 8358902 TI - Acromioclavicular joint cyst associated with rotator cuff tear. A report of three cases. AB - Acromioclavicular joint cyst (AJC) is a rare condition, usually occurring in the presence of a wide communication between glenohumeral and acromioclavicular joints in patients with a massive rotator cuff tear. In the presence of AJC, accurate evaluation of the status of the rotator cuff should always be made. Removal of the cyst only must be avoided because the condition tends to recur if the cuff tear is not repaired. When the tear is so large that it cannot be repaired, excision of the cyst should be associated with a resection of the lateral end of the clavicle. PMID- 8358903 TI - A prospective randomized study of a collar versus a collarless femoral prosthesis. AB - A prospective, randomized study of 44 collared versus 40 collarless cemented HD-2 total hip arthroplasties (THAs) was performed in 84 patients. Seventy patients were examined at an average of 4.6 years after surgery. Five hips have required, or are scheduled to have, revision arthroplasty: two with collared prostheses and three with collarless prostheses. Good collar contact with the proximal medial femur was achieved in 47% of the collared prostheses. No patient with good contact has required or is scheduled to have revision hip surgery. Radiolucent lines were greater in both frequency and width in Gruen Zones 2 and 7 in patients with a collarless prosthesis. Loss of endosteal height of the femoral neck was 3.5 mm in patients with collarless prostheses and 1.7 mm in patients with collared prostheses. Loss in height of the femoral neck was 2.6 mm in patients with collared prostheses with poor bone contact and 0.7 mm in patients with collared prostheses with good bone contact. The mean preoperative and postoperative Harris hip scores for the collarless group and for the collared group were not statistically different. There were no statistically significant differences in acetabular position, the incidence of acetabular radiolucent lines, or femoral subsidence between patients treated with collared or collarless prostheses. This study demonstrates that it is possible to stress the proximal medial portion of the femur with a collared prosthesis. Furthermore, a significant increase is identified in both the frequency and width of radiolucent lines in patients with collarless prostheses in Zones 2 and 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8358904 TI - The uncemented Gerard bipolar double-cup arthroplasty of the hip. A five- to 11 year follow-up study. AB - Between 1978 and 1984, 183 hips in 154 patients with the uncemented Gerard double cup arthroplasty were resurfaced. The clinical and radiographic results of the 106 original arthroplasties were reviewed after a median follow-up period of 98 months. Although many of these patients had clinically improved immediately, the Harris Hip score decreased significantly in most hips in subsequent years. No correlation was found between the clinical score and radiographic complications. Major revision surgery with removal of the double cup was performed in 54 of 183 patients, making the cumulative success rate after 132 months only 48%. Survival was significantly greater in patients younger than 50 years of age and in patients with a low body weight (Quetelet index less than 25). This high failure rate eliminates the Gerard double-cup arthroplasty, except possibly for the patient with a destructive inflammatory arthropathy for whom there are no other surgical alternatives. PMID- 8358905 TI - Survivorship analysis of cemented high modulus total hip arthroplasty. AB - Ninety-four high-modulus total hip arthroplasties (THAs) were performed from 1977 to 1982 using the Computer Assist Design (CAD) and HD-2 prostheses. Eighty-six hips were followed for an average of 6.7 years. The cement gun was used throughout the study period, and distal bone or cement plug use was begun in 1979. The results of these arthroplasties were evaluated retrospectively using both survivorship analysis and observed success rates. Using a standard hip rating system, 19 hips were rated as excellent, 44 as good, 15 as fair, and 11 as poor. Failure was defined as definitely visible radiographic migration of either component, or reoperation for revision of one or both components. There was no significant difference between the HD-2 and CAD prostheses. There were five hips revised for aseptic loosening and revision was advised in an additional three hips. One hip with late sepsis required removal of both components. The five- and ten-year survivorships of the acetabular components were 97% +/- 3 and 58% +/- 17, respectively. Those of the femoral components were 93% +/- 5 and 78% +/- 13, respectively. For the components combined, the survivorship at five years was 91% +/- 6 but only 50% +/- 17 at ten years. Survivorship analysis provided a different and more realistic appraisal of the long-term results of the arthroplasties in this series than did the observed success rates. The contemporary cement techniques of the late 1970s and early 1980s may not be sufficient for the long-term survival of high-modulus THAs. Additional techniques may be necessary for improved long-term survival. PMID- 8358906 TI - Total hip arthroplasty in sickle cell hemoglobinopathy. AB - Twenty-two arthroplasties were performed in 14 patients with sickle cell hemoglobinopathy (SCH). There were 15 primary and seven revision procedures; none were lost to follow-up evaluation. In the primary arthroplasty group, there were two deaths in patients whose implants were functioning well. The remaining 13 hips had a mean follow-up period of 4.8 years. Failure occurred in five of these 13 hips (38%), four due to aseptic acetabular loosening and one due to sepsis. In the revision arthroplasty group, at a mean follow-up period of 5.3 years, failure occurred in three hips (43%), one due to acetabular loosening, one due to femoral loosening, and one due to sepsis. Perioperative complication rates were high in both groups. Femoral intramedullary sclerosis and bone altered by marrow hyperplasia were associated with intraoperative technical difficulties as well as problems with achieving long-term component fixation. Though total hip arthroplasty provides the most reliable measure of effective treatment in SCH, it carries a high risk of complications and failure. PMID- 8358907 TI - Total hip arthroplasty in beta-thalassemia. Case report and review of the literature. AB - A 60-year-old man with beta-thalassemia intermedia and degenerative joint disease was successfully treated by total hip arthroplasty. The operation was complicated by severe bleeding associated with marked bone marrow hyperplasia. Despite autologous cell salvage, massive homologous transfusion was required. Special orthopaedic and perioperative complications stem from beta-thalassemia syndromes. Management may be complicated by anemia, medullary hyperplasia, organ dysfunction associated with iron overload, and susceptibility to infection. The orthopaedic manifestations of beta-thalassemia may be mitigated by chronic transfusions. PMID- 8358908 TI - Chevron osteotomy and single wire reattachment of the greater trochanter in primary and revision total hip arthroplasty. AB - Even at a medical center where hip arthroplasty is performed routinely without trochanteric osteotomy, selected arthroplasties still require greater trochanteric osteotomy. A technique of greater trochanteric biplane osteotomy and reattachment with one wire is described. The technique provides maximum stability with a minimum of internal fixation and it can be performed quickly. The postoperative rehabilitation protocol is the same as that used in hip arthroplasty patients without trochanteric osteotomy. Results with a minimum two year follow-up period disclosed osseous union in 98% of 53 primary arthroplasties and 97% of 74 revision hip arthroplasties. Problems related to the greater trochanter necessitated reoperation in only two patients: one for reattachment of a migrated trochanter and one for trochanteric wire removal. PMID- 8358909 TI - Extensile triradiate approach for complex acetabular reconstruction in total hip arthroplasty. AB - The triradiate approach as described by Mears has been used for open reduction of complex dual-column acetabular fractures. Mears extended the anterior limb of this incision to the symphysis pubis by the ilioinguinal approach. From a consecutive series of 43 total hip revisions, this approach was used successfully in seven cases in which extensile exposure was necessary to revise complicated acetabular reconstructions for arthroplasty. The approach was used also to perform complex acetabular reconstruction after en bloc tumor resection. Three patients had severe intrapelvic component protrusio and anterior column deficiency where close proximity of the prosthesis and femoral neurovascular bundle were detected before surgery. Massive allograft and pelvic reconstructions were used to span large anterior column defects and to stabilize pelvic dehiscence. Complications included one hip dislocation and one posterior flap tip necrosis. Follow-up ranged from six to 34 months. No graft failure has been noted. PMID- 8358910 TI - Pelvic reconstruction/total hip arthroplasty for metastatic acetabular insufficiency. AB - Four cases of pathologic periacetabular insufficiency/fracture in patients with extensive neoplastic metastatic involvement of the hemipelvis were treated by pelvic reconstruction with hemipelvis pin reinforcement with total hip arthroplasty (THA). Reconstruction was reserved for patients with limited other bony or visceral metastases, and had extreme narcotic-dependent pain and debilitation, or failed prior management, but had reasonable life/activity expectancy. Tumor palliation and hemipelvis reconstruction was obtained by ilioinguinal (pelvic) and posterolateral (hip) incisions. Iliac crest exposure allowed iliacus elevation, debulking of any intrapelvic soft-tissue mass, and exposure of the medial acetabulum. Rows of threaded Steinman pins were selectively passed from iliac crest (ilioinguinal incision) to superior and medial acetabular deficiencies (hip incision) in guided antegrade fashion. A reinforced polymethylmethacrylate (PMMA) acetabular reconstruction was then created, with PMMA incorporating medial and superior pins, an anti-protrusio ring, and a standard cemented acetabular component. A long-stem cemented femoral component was placed for proximal femoral metastasis prophylaxis. Postoperative rehabilitation (mean hospitalization, 12.7 days) was as for cemented THA. Mean survival was 15 months with integrity of the hip construct maintained throughout. All four patients progressed to independent ambulation with walking aids and were gratified that they had elected surgical treatment with reconstruction. PMID- 8358911 TI - Ununited femoral neck fractures by open reduction and vascularized iliac bone graft. AB - Neglected femoral neck fractures are frequently complicated with nonunion and avascular necrosis of the femoral head. The treatment is especially difficult in young adults because arthroplasty is not indicated. Five cases of neglected femoral neck fractures in young patients were treated by open reduction and internal fixation with pins. The defect of the femoral neck was filled with a block of vascularized iliac bone graft. After at least two years, the fractures were healed without avascular necrosis of the femoral head. The leg-length discrepancy was corrected in all but one case. The pedicled iliac graft provided a viable bone graft, which maintained the viability of the head and hastened fracture healing. PMID- 8358912 TI - Intertrochanteric fractures of the femur in rheumatoid arthritis patients. AB - In a series of 33 intertrochanteric femoral fractures in patients suffering from classic rheumatoid arthritis (RA), the typical patient was about 70 years of age, osteopenic, and severely affected by longstanding polyarticular RA of joints other than the hip. Prefracture involvement of the hip joint (other than osteopenia) was apparent radiographically in only 9.1% of patients. There was a higher rate of avascular necrosis (9.7%) and nonunion (6.5%) than expected in the nonrheumatoid general population. There was also a high rate of secondary displacement. Of three patients with avascular necrosis, two had had corticosteroid treatment. PMID- 8358913 TI - Walking ability after internal fixation of trochanteric hip fractures with Ender nails or sliding screw plate. A comparative study of gait. AB - The influence of several clinical and radiographic parameters on the functional outcome of 92 patients with trochanteric hip fractures treated at random with either Ender nails or a sliding screw plate (SSP) was prospectively investigated. Apart from other clinical variables such as pain, the use of walking aids, and walking distance, the walking ability of patients was assessed by gait analysis performed on an electronic walkway. The parameters investigated were the maximal vertical force (MVF) and single-limb support phase (SLS). Independent of the type of fixation, no differences were observed between stable and unstable fractures in any of the parameters analyzed six months after surgery. In fractures treated with Ender nails, the use of walking aids and MVF were influenced by a satisfactory fracture reduction. Walking distance was the sole factor correlated with the status of fracture healing. In fractures treated with SSP, the pain was the only clinical variable significantly influenced by the outcome of fracture healing. In trochanteric fractures treated with Ender nails, the quality of fracture reduction was the most valuable predictor of patients' recovery of walking ability. PMID- 8358914 TI - Avascular necrosis of the femoral head as sequela of fracture of the greater trochanter. A case report and review of the literature. AB - After a fall from a tree, a 12-year-old boy sustained a fracture of the greater trochanter and was subsequently treated by open reduction. Twenty months after surgery, the hip developed to a flexion contracture, limb-length discrepancy, a collapsed, irregular-shaped femoral head with sclerotic areas, and a metaphyseal cyst. A growing child with avascular necrosis of the femoral head after fracture of the greater trochanter seems not to have been reported in the English language literature. PMID- 8358915 TI - Classification in slipped capital femoral epiphysis. Sonographic assessment of stability and remodeling. AB - In a prospective study of 26 hips in 21 patients with slipped capital femoral epiphyses (SCFEs), serial sonography was more sensitive than radiography in showing epiphyseal displacement and reduction. Reductions were associated with grossly visible hip joint effusions. The initial slips were reduced by treatment in seven of 11 hips with effusion. The 15 hips without effusion were unreduced. After stabilization and pinning, the effusion did not recur in any case. Sonography is sensitive and free from projectional errors in the assessment of metaphyseal remodeling. If any remodeling is present, the SCFE is at least three weeks in duration. A new classification into acute, acute-on-chronic, and chronic SCFEs is proposed, based on the objective sonographic data. Joint effusion represents physeal instability or recent progression, and remodeling is a sign of chronicity. An acute SCFE is characterized by effusion, whereas a slip without effusion but with remodeling is designated as chronic. An acute-on-chronic SCFE is associated with both effusion and remodeling. Joint effusion suggests that SCFEs should be operatively fixed and that displacement may diminish with traction or intraoperative positioning of the hip. PMID- 8358916 TI - Long-term results of valgus osteotomy for congenital coxa vara. AB - Twenty hips (12 patients) with congenital coxa vara, treated with valgus subtrochanteric osteotomy, were reviewed retrospectively. The average Hilgenreiner-epiphyseal (HE) and head-shaft (HS) angles at the initial evaluation were 66 degrees and 96 degrees, respectively. The average postoperative follow-up time was 20 years. Five of the 12 hips with trochanteric overgrowth had abductor weakness. A postoperative HE angle of 35 degrees or less and a HS angle of 130 degrees or more was correlated with consistently satisfactory results. PMID- 8358917 TI - Sensitivity of manual palpation in testing the neonatal hip. AB - Developmental dysplasia of the hip (DDH) is a term used to describe a group of disorders of the neonatal hip in which the head of the femur is unstable or incongruous in relation to the acetabulum. Early detection and treatment of the condition generally results in normal development, whereas late diagnosis has poor success. In Northern Ireland, despite all neonates being manually examined for hip disorders by a medical officer before hospital discharge, there is an unacceptable late diagnostic rate of almost 50% of all cases. To help reduce the number of late presentations, vibration arthrometry, a noninvasive form of screening for DDH, has been used to record hip vibration events during clinical testing. In a comparative study, 300 infants were examined by nurses and medical officers to establish the sensitivity of manual palpation to neonatal hip vibrations detected by the objective detection system. Experienced research nurses detected 86% of the signals; doctors in training detected less than 10%. This suggests that objective, noninvasive screening by vibration arthrometry would detect a higher proportion of vibration events in neonates during the early stages of DDH. More time should be invested in training medical officers and others involved in DDH screening. PMID- 8358918 TI - Nine-year follow-up results of two methods of MacIntosh anterior cruciate ligament reconstructions. AB - Forty-seven MacIntosh anterior cruciate reconstructions using iliotibial band were performed in patients with chronic instability symptoms and positive pivot shift jerk. In 22 knees, a lateral substitution technique alone was used. In 25 knees, the technique was supplemented with an intraarticular component. After an average of follow-up of nine years, 62% of knees had an excellent or good Lysholm score; 83% of patients remained active in sports. Subjectively, there was no deterioration of stability with time, and no return of the jerk on pivot shift testing, although a slide persisted in one third of the patients. The addition of an intraarticular component did not alter the subjective result. Objectively, the trend was toward improvement in functioning. The lateral tenodesis was the major determinant in the improvement of subjective stability and control of pivot shift jerk. PMID- 8358919 TI - Gait analysis study on patients with varus osteoarthrosis of the knee. AB - Biomechanical changes that occur after high tibial osteotomy (HTO) was investigated in 30 patients with osteoarthrosis (OA) of the knee and 11 age matched normal subjects. Of the 37 knees with varus OA evaluated, 21 were analyzed before and after surgery (average follow-up evaluation, two years). The mean age of the patient group was 58.2 years. Clinical assessment was based on the Hospital for Special Surgery (HSS) knee scoring system. Full-length weight bearing radiograms were taken for the measurement of the mechanical axis of the lower limb. Results from clinical assessment showed that 90% of the patients had good or excellent postoperative clinical results, as opposed to 9.5% before surgery. An overall improvement in the gait parameters was evident in the group evaluated after surgery, although control levels were not attained. Further analysis based on moments about the knee showed that 57% of the surgically treated knees with good or excellent clinical results had abnormal load distribution. This may lead to deterioration in the future, and further surgery may be required. The abnormal loading was also reflected in the ground-reaction force vector diagram. Therefore, the force vector diagram can be used as a quick screening method to detect abnormal joint loading. PMID- 8358920 TI - Experimental studies of osteopetrosis in laboratory animals. AB - Osteopetrosis is a metabolic bone disease characterized by a systemic increase in skeletal mass. It results from a defect in the production or function of osteoclasts and is inherited in nine genetically distinct osteopetrotic animal mutations and man. Studies of these mutations have revealed that osteopetrosis is a complex, heterogeneous disorder in its expression, etiology, and response to treatment by bone marrow transplantation or by hormone/growth factor therapy. These animal mutations have been valuable tools for probing the pathogenesis and treatment of osteopetrosis, and information obtained from these studies has been used clinically for the treatment of humans with osteopetrosis. In addition, studies of these mutations have contributed significantly to understanding normal bone cell biology, including the origin of the osteoclast and the significance of colony-stimulating factor-1 in osteoclast development. The resistance of some of these mutations to cure by stem cell transplantation and hormone therapy, coupled with similar observations and experiences in the human condition, indicates that these animal mutations will continue to serve important roles in the development of alternative therapies to treat resistant forms of the disease. These studies are bound to improve the understanding of normal bone biology by providing additional insights into the regulation of osteoclasts by osteoblasts and their products or by other elements of the skeletal microenvironment. PMID- 8358921 TI - Early weight bearing of lateral tibial plateau fractures. AB - From 1975 to 1984, 134 consecutive lateral tibial plateau fractures were treated as part of this prospective study. Eighty-six fractures (64%) were followed until union, with an average follow-up period of 22.7 months. The two aims of this study were: First, to analyze the results of operative and nonoperative therapy in each fracture type, and second, to evaluate the effect of early weight bearing in a cast brace in both types of treatment. All lateral tibial plateau fractures with greater than 5 mm depression or displacement were treated operatively. Forty four patients were treated operatively and 42 patients nonoperatively. All patients were treated with early range of motion and weight bearing in a cast brace. Fractures were initially classified using Hohl's classification system. Overall, 95% of the patients with Type I, II, or V fractures had satisfactory results, as opposed to only 70% of patients with Type III fractures. Of the Type III fractures, 83% treated operatively had satisfactory results compared with 53% treated nonoperatively. Moreover, early weight bearing did not produce further depression greater than 2 mm. PMID- 8358922 TI - Knee arthrodesis using combined intramedullary rod and plate fixation. AB - Intramedullary arthrodesis of the knee is a satisfactory method for treating difficult salvage cases of infected arthroplasty, bone loss, and severe osteoporosis. In eight cases, a medial compression plate was routinely used for complete fixation. Union occurred in all cases, including two proximal tibial segmental allografts. Five previously infected cases were healed at follow-up examination (average, six to 44 months). Complications included proximal rod prominence, partial peroneal nerve palsy, recurrent sepsis in one case, and tibial shaft perforation on nail insertion. Seven of the eight patients used some form of walking aid for extended ambulation. Leg length was generally 1.5-2.5 cm shorter than the opposite limb. PMID- 8358923 TI - Arthroscopic treatment of anterior cruciate ligament avulsion. AB - A new technique is described for arthroscopic reduction and internal fixation (ARIF) of avulsion fractures involving the insertion of the anterior cruciate ligament (ACL). Conventional methods of treatment of ACL avulsion in adults may lead to suboptimal results owing to stiffness from either prolonged immobilization or the morbidity of arthrotomy. Contemporary techniques of arthroscopic reduction and percutaneous pinning do not achieve rigid fixation and thus still require cast immobilization. The placement of cannulated screws through the anteromedial arthroscopic portal provides rigid fixation while avoiding arthrotomy, allowing early mobilization and return to activity. The possibility of interstitial damage to the ACL and implications regarding tensioning of the ligament are considered A typical case illustrates ARIF of ACL avulsion. The technique minimizes morbidity and optimizes function. PMID- 8358924 TI - Unicompartmental arthroplasty for osteonecrosis of the knee joint. AB - A review of 34 knees with osteonecrosis of the medial femoral condyle treated by unicompartmental arthroplasty is presented, with a minimum of two years' follow up time and an average of five-and-one-half years. Excellent or good results were obtained in 89% of the patients. Of the four failures reported, two were caused by the development of osteonecrosis of the lateral compartment. Two other patients had persistent pain with no apparent cause. Unicompartmental arthroplasty is acceptable treatment of osteonecrosis of the knee joint because of the rapid recovery from the operation, the low morbidity rate, and the preservation of the cruciate ligaments, the patella, and the opposite compartment, which results in better function and motion than a high tibial osteotomy or a total knee arthroplasty. PMID- 8358925 TI - The Maquet procedure in the treatment of patellofemoral osteoarthrosis. Long-term results. AB - Long-term results are reported for 35 knees with patellofemoral osteoarthrosis treated by Maquet procedure. Eighty percent were rated very good or good, and 20% fair or poor. The poor results are attributed to errors in the diagnosis or to inadequate surgical technique. The Maquet procedure thus provides good results for painful knees with patellofemoral osteoarthrosis. A tibial tubercle elevation of at least 2 cm is necessary to decrease joint pressure sufficiently. PMID- 8358926 TI - Alveolar soft-part sarcoma. A report of ten cases. AB - The clinical and pathologic features of ten cases of alveolar soft-part sarcoma (ASPS) were observed in subjects aged ten to 49 years. Eight were male and two were female. The lesion involved the thigh in six cases and the adjacent bone in three. All lesions were retrospectively classified as high risk (Stage II or III of Enneking's staging system), and distant metastasis to lung or bone was noted at initial presentation in four patients. Three patients died with distant metastases at a mean time of three years seven months after diagnosis. The mean interval from initial presentation to detection of distant metastasis was nine months; and the mean interval from detection of metastasis to death was three years two months. Ultrastructural studies demonstrated typical organoid arrangement of the neoplastic cells surrounded by a basement membrane with close attachment of individual cells to the basal lamina. No local recurrence, even in cases with inadequate tumor control, and the tendency for distant metastasis demonstrated in the current series, reemphasized that management of metastasis is most important in the treatment of ASPS. PMID- 8358927 TI - Massive osteolysis. AB - Massive osteolysis is rare, peculiar, and enigmatic. The clinical, radiographic, and histologic features were reviewed in 11 cases. The patients were generally young (mean age, 20.7 years), and males outnumbered females. More than half the patients had involvement of either the femur or the ribs alone or including the vertebrae. On the basis of radiographic studies, the disease process is capable of originating either in bone or adjacent soft tissues. Histologically, the authors were unable to identify pathognomonic features. Other than excision of all involved tissue, surgical treatment was generally ineffective. Radiation therapy may be successful in eradicating the disease in selected cases. PMID- 8358928 TI - Enchondroma in a patient with fibrodysplasia ossificans progressiva. AB - Fibrodysplasia ossificans progressiva (FOP) is a rare heritable disorder characterized by progressive heterotopic endochondral bone formation arising in ligament, tendon, and the fibrous connective tissue of skeletal muscle. The disorder is almost invariably associated with skeletal malformations of the endochondral anlage of the feet. A 25-year-old woman with FOP had a histopathologically documented phalangeal enchondroma. This common neoplasm of cartilage and bone seems not to have been previously reported in FOP; it may represent a coincidental occurrence, but in the context of the patient's genetic disorder, an enchondroma may represent an unusual and variable expression of the disease. PMID- 8358929 TI - Chondrosarcoma treated by reimplantation of resected bone after autoclaving and supplementation with allogeneic bone matrix. A case report. AB - An extensive intramedullary lesion of the femur was diagnosed as a Grade I chondrosarcoma in 1986. At definitive surgery, four fifths of the femoral diaphysis were resected, autoclaved, and reimplanted. The reconstruction, after stabilization with AO plates, was supplemented with allogeneic bone matrix to induce new bone formation. No autografts were used. Despite subsequent infection and sequestration of the autoclaved tumorous segment, the reconstructed area was gradually enveloped by new bone. Three years after primary surgery, the infection persisted. The AO-plated and autoclaved sequestered bone was excised. Six years after the operation, the patient walks bearing full weight and works full time. There are no signs of tumor recurrence. PMID- 8358930 TI - Total sacrectomy for a giant sacral schwannoma. A case report. AB - Giant sacral schwannomas (GSS) are extremely rare. Complete resection of benign but neurologically devastating tumors has been recommended. A 48-year-old man with GSS had a tumor so large that a total sacrectomy was necessary. A special method of lumbar iliac fixation was devised. Two years and nine months after surgery, the patient was free of pain and ambulating with bilateral orthoses. PMID- 8358931 TI - Multiple myeloma in a 25-year-old woman. AB - A 25-year-old woman with acute knee pain and a lytic area in the proximal femur was diagnosed as having multiple myeloma (MM). This case is one of only eight in patients younger than aged 30 years to meet modern diagnostic criteria for MM. Failure to consider MM in young individuals precludes early diagnosis and valuable time for treatment. PMID- 8358932 TI - Pfeiffer's syndrome family tree. Review of the literature. AB - Pfeiffer's syndrome is an autosomal dominant disorder characterized by craniofacial abnormalities and distal extremity abnormalities. This case study reviews four generations of a family with craniofacial abnormalities, multiple simple syndactylies, and delta phalanges of bilateral great toes and thumbs inherited in an autosomal dominant fashion. PMID- 8358934 TI - Coronal-plane transcondylar fracture of the humerus in a child. AB - A coronal plane fracture of the distal humerus in a child is an uncommon fracture, with the most familiar example being a capitellar fracture. An unusual coronal fracture of the entire distal humeral articular surface (capitellum and trochlea) occurred in a three-year-old boy. This fracture pattern has been described in adults but is believed to be previously unreported in children. This Salter-Harris Type IV fracture was initially misdiagnosed as a lateral humeral condyle fracture. Three years after treatment with open reduction and pin fixation, the distal humerus shows no evidence of growth disturbance. PMID- 8358933 TI - Triple arthrodesis using internal fixation in treatment of adult foot disorders. AB - Forty adult patients with 44 fused feet were evaluated at an average of 4.9 years after triple arthrodesis. The average age of the patients at operation was 41 years. All operations were performed by a specific technique using rigid internal fixation with screws. Outcome was graded using the clinical criteria of Hallgrimsson as modified by Angus and Cowell. Function was evaluated according to modified Arthritis Impact Measurement Scales (AIMS). Radiographic evaluation included measurement of lateral talocalcaneal angle, lateral talometatarsal angle, and anteroposterior (AP) talometatarsal angle on standing or simulated weight-bearing radiographs. Thirty-four feet had good results, six had fair results, and there were four failures. The average patient could function painlessly on flat surfaces in nonstrenuous activities and had only occasional mild pain with more vigorous activities. In roentgenographic parameters, there was an average improvement of 17 degrees in the lateral talometatarsal angle, 11 degrees improvement in the lateral talocalcaneal angle, and an improvement of 18 degrees in the AP talometatarsal angle. There were two pseudarthroses, no recurrences, and two unsatisfactory corrections. When carefully done, triple arthrodesis can restore an adult patient with a disabling foot disorder to normal function and minimal pain. PMID- 8358935 TI - Transverse divergent dislocation of the elbow in a child. A case report. AB - The transverse divergent dislocation of the elbow in the child is a rare occurrence. In a ten-year-old boy, divergent dislocation was associated with a fracture of the coronoid process and of the radial epiphysis. After a closed reduction and plaster immobilization, full function of the elbow was recovered within nine months. PMID- 8358936 TI - Synthetic posterior cruciate ligament reconstruction and below-knee prosthesis use in Ehlers-Danlos syndrome. AB - Ehlers-Danlos syndrome (EDS) has been associated with irreparable arterial disruption, spontaneous and traumatic, necessitating amputation. Recurrent and chronic joint dislocation is a common component. Because of the very thin, hypermobile skin and "tissue paper scars," these patients would be expected to be poor candidates for the use of lower extremity prostheses. A review of the literature failed to show any reports of lower extremity prosthesis use in EDS patients or of recurrent and chronic joint dislocation treated by synthetic ligament reconstruction. The case of a 21-year-old woman is an example of both. PMID- 8358937 TI - Two patterns of calcification in primary (physeal) and secondary (epiphyseal) growth cartilage. AB - It is generally stated that the process of cartilage calcification and ossification is the same in the physeal (primary growth center) and epiphyseal (secondary growth center) growth plates. Reexamination of osteophyte growth led to the proposal that these growth plates differ. This proposition was tested by examining rabbit and human material from both sites before and after maceration; both tissue preparations were processed for light microscopy, and the macerated tissues were also studied by scanning electron microscopy (SEM). The physis showed the well-recognized, longitudinal calcified tubal structures in which capillaries make direct contact with and resorb the nonmineralized, transverse septal cartilage. In the epiphysis, the transverse septal cartilage was also mineralized, producing a continuous calcified sheet, perforated only by a limited number of channels and susceptible only to osteoclastic removal. This variation in mineral distribution modifies the way in which the primary spongiosa is formed during growth. PMID- 8358938 TI - Delayed implantation of demineralized bone powder after local irradiation in rats. AB - Previous studies have shown that osteoinduction is inhibited when demineralized bone powder (DBP) is implanted within 48 hours of local irradiation (i.e., when the acute effects of radiation injury are present). This study sought to determine whether normal osteoinduction can proceed if the implantation of DBP is delayed until 21 days postirradiation. At 21 days, the acute effects of radiation injury are likely to have subsided, but the long-term effects have not yet appeared. Twenty-eight-day-old rats were administered a radiation dose of either 7 or 20 Gy over a localized area of one thigh. The contralateral, nonirradiated thigh served as a control. Demineralized bone powder was subcutaneously implanted 21 days later. Subcutaneous pellets were retrieved at various intervals thereafter (up to Day 45) and were histologically graded for evidence of osteoinduction. No difference in osteoinduction was detected at any time interval in pellets from the 7-Gy-treated sites, compared with controls. Pellets from the 20-Gy-treated sites, however, demonstrated significantly a lower osteoinductive response at each interval. These latter pellets showed small scattered areas of osteoinduction and reduced formation of marrow elements. Thus, although osteoinduction proceeds normally when the implantation of DBP is delayed for 21 days after irradiation with 7 Gy, this is not the case when 20 Gy are administered. Given the absence of gross impairment of tissue vascularity in irradiated sites, it is possible that inhibition of osteoinduction after higher doses of radiation results from permanent damage to mesenchymal precursor cells. PMID- 8358939 TI - Polylactic acid-polyethylene glycol block copolymer. A new biodegradable synthetic carrier for bone morphogenetic protein. AB - A new biodegradable polymer, a polylactic acid-polyethylene glycol (PLA-PEG) block copolymer, proved to be an effective and suitable carrier for bone morphogenetic protein (BMP). Composites of semipurified BMP and PLA-PEG consisting of a PLA segment with a molecular weight (MW) of 650 d and a PEG segment with a MW of 200 d (PLA-PEG 650-200) were implanted under the fasciae of the dorsal muscles of mice. Three weeks after implantation, the PLA-PEG 650 200/BMP composites were completely absorbed and replaced by newly induced bone with hematopoietic marrow. The composites induced twice as much bone as composites of BMP and a 650-d PLA homopolymer. Results indicate that of all the biodegradable synthetic polymers the authors have tested, PLA-PEG 650-200 is the most suitable and effective BMP carrier. Composites of PLA-PEG 650-200/BMP and hydroxyapatite powder (HAP) also induced ectopic bone formation. Because PLA-PEG 650-200/BMP is viscous and semiliquid and PLA-PEG 650-200/BMP/HAP is doughy and plastic, the former can be used as an injectable osteoinductive material and the latter as a plastic mold. PMID- 8358940 TI - Osteopetrosis. Current clinical considerations. AB - Osteopetrosis is an inherited skeletal condition characterized by increased bone radiodensity. There are three clinical groups: infantile-malignant autosomal recessive, fatal within the first few years of life (in the absence of effective therapy); intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course; and autosomal dominant, with full life expectancy but many orthopaedic problems. The infantile variant shows a myelophthisic anemia, granulocytopenia, and thrombocytopenia, and patients eventually die from infection or bleeding or both. Neurologic sequelae include cranial nerve compression (optic nerve, blindness; auditory nerve, deafness; facial nerve, paresis), hydrocephalus, convulsions, and mental retardation. Radiographs show uniform bone density without corticomedulary demarcation, broadened metaphyses, "bone within a bone" or endobone phenomena (tarsals, carpals, phalanges, vertebra, ilium), and thickened growth plates if there is superimposed rickets. Transverse pathologic fractures occur, often followed by massive periosteal bone formation. Computed tomographic scans, magnetic resonance imaging, and bone scans provide specific information. Iliac crest bone biopsy is valuable to quantitate osteoclast and marrow changes by light and electron microscopy. Medical treatments involve high-dose calcitriol to stimulate osteoclast differentiation and bone marrow transplantation to provide monocytic osteoclast precursors. Orthopaedic problems in the intermediate and autosomal dominant forms include increased fractures, coxa vara, long-bone bowing, hip and knee degenerative arthritis, and mandibular and long-bone osteomyelitis. Cranial nerve compression also occurs. Osteotomy, plating, intramedullary rodding, and joint arthroplasty can be done, but are difficult because of bone hardness. PMID- 8358941 TI - Gene cloning and expression of a bone morphogenetic protein derived from a murine osteosarcoma. AB - Based on information from partial amino acid sequences of a protein with bone inducing activity that was purified from a murine osteosarcoma (Dunn type), a cDNA library of the sarcoma was screened to clone a gene complementary to the protein. The cloned cDNA was amplified and transfected into Chinese hamster ovarian (CHO) cells for expression. When the protein produced by the transfected cell line was implanted in combination with pure carrier collagen into allogeneic mice, ectopic ossicles consistently developed at implanted sites within two weeks. The nucleotide sequence of the cDNA and its deduced amino acid sequence were homologous to those of human bone morphogenetic protein-4 (also BMP-2B). In addition, the cDNA and deduced amino acid sequences were identical to those proposed for murine BMP-4 derived from the normal murine fetus. It is postulated that the cloned cDNA encodes the protein responsible for bone formation induced by implantation of devitalized Dunn-type osteosarcoma tissue or cells. The protein product was identified as murine BMP-4, a member of the TGF-beta gene family. PMID- 8358942 TI - Establishment of a cell line from a human giant cell tumor of bone. AB - A cell line (CG-1) was established from a specimen of a 21-year-old woman with giant cell tumor of bone. Inverted-phase microscopic analysis showed that the cultured cells were spindle-shaped in appearance. Multinucleated giant cells and macrophagelike round cells characterizing the histology of giant cell tumor of bone were not found. It is believed that the spindle-shaped cells were the neoplastic element of this tumor, because they were cultured more than 40 passages over the course of one year and subsequent cytogenetic analysis with a G band technique showed constant loss of chromosomes 14 and 19. The cell line was found to produce several cytokines: M-CSF, IFN-gamma and TNF-alpha, as demonstrated by Western blotting analysis. These cytokines are known to show chemotactic, differentiation-inducing, and activating effects on macrophages. Because it has been recently reported in the literature that there are many infiltrated macrophages in giant cell tumor of bone, and because multinucleated giant cells are formed by fusion of macrophages, the newly established cell line may prove a useful system in studying the nature of giant cell tumor of bone. PMID- 8358943 TI - Characteristics of metal and ceramic total hip bearing surfaces and their effect on long-term ultra high molecular weight polyethylene wear. AB - The micromechanics of ultra high molecular weight polyethylene (UHMWPE) wear in total hip replacement are very complex. Polyethylene wear from the metal head and debris formation are two common types of wear. There are additional wear-related processes occurring at the metal-bearing surfaces that are not well-known, however. This study outlines these processes, including (1) surface wettability changes, (2) oxidative wear of metal surfaces, (3) microabrasion of metal surfaces from oxide film damage, and (4) surface abrasion from three-body polymethylmethacrylate and bone debris. These processes can contribute to metal ion release and a gradual increase in the roughness of the metal surfaces. This can lead to increased long-term UHMWPE wear. Of the metal alloys currently used in total hip replacements, Co-Cr-Mo alloy is significantly more resistant to roughening processes. Hard, stable, oxide: ceramic surfaces articulating against UHMWPE are essentially immune to these surface-roughening processes, however. In addition, they provide a more wettable surface, further minimizing polyethylene wear relative to metal surfaces. By analyzing metal release rates from metal polyethylene wear tests, it is shown here that Co-Cr-Mo is gradually removed at a rate of about 0.1 micron per year (10(6) cycles), whereas 316L stainless steel is removed on the order of 0.2 microns per year and Ti-6Al-4V on the order of 1 micron per year. The wear rate of Co-Cr-Mo articulating against itself is reported to be still greater, at about 2-4 microns per year after an initial wear in period. Because metal is gradually removed with articulation time, surface hardening methods such as nitrogen ion implantation can be expected to provide only temporary resistance to these metal removal and surface-roughening processes. Hard, stable ceramic surfaces such as Al2O3 and ZrO2, however, can be expected to maintain their initial surface finish and thus minimize UHMWPE wear in the long term. PMID- 8358944 TI - Quadriceps/anterior cruciate graft interaction. An in vitro study of joint kinematics and anterior cruciate ligament graft tension. AB - The Oxford Rig, a device that simulates active knee extension during stance, was used to study the effects of quadriceps force on AP tibial displacement and axial tibial rotation in vitro. Human anatomic specimen knees were tested with the anterior cruciate ligament (ACL) intact, sectioned, and reconstructed. Patellar tendon grafts used in the ACL-reconstructed state were attached distally to a load cell, allowing direct measurement of graft tension. Both ACL status and quadriceps force had significant effects on anterior tibial displacement, limits of AP displacement, axial tibial rotation, and graft tension, as shown by analysis of variance. Anterior cruciate ligament sectioning led to anterior tibial displacement in the absence of quadriceps force, whereas ACL reconstruction led to posterior tibial displacement. In the ACL-intact, quadriceps-stabilized state, anterior displacement of the tibia was observed between 95 degrees flexion and full extension, with a maximum displacement (3.5 +/- 0.2 mm) between 30 degrees and 45 degrees flexion. After ACL sectioning, anterior tibial displacement resulting from quadriceps force was accentuated relative to the intact state by as much as 4.5 mm +/- 0.9 mm at 20 degrees and 25 degrees flexion. Anterior tibial displacement in the ACL-intact and reconstructed specimens was similar when quadriceps force was present. In the quadriceps stabilized state, graft tension increased between 5 degrees and 80 degrees flexion. The maximum increase in graft tension due to quadriceps force was at 35 degrees flexion. PMID- 8358945 TI - Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells. 1975. PMID- 8358946 TI - Autosomal dominant osteopetrosis. AB - Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, primarily involving the axial skeleton, and by symmetrical affections of the long bones without modeling defects. Based on standard radiographs, it is possible to describe two different subtypes with different clinical, biochemical, and histologic manifestations. Type I is radiographically characterized by pronounced osteosclerosis of the cranial vault, whereas Type II has end-plate thickening of the vertebrae (Rugger-Jersey spine) and endobones in the pelvis. Both types are strictly family related and seen in childhood. Combined radiogrammetric, biochemical, and histologic investigations indicate states of defective bone resorption, whereas bone formation seems to be normal in both types of patients. Patients with autosomal dominant osteopetrosis are often asymptomatic, and the diagnosis may be reached by chance. However, by systematic investigations, nearly all patients have manifestations related to the disorder. Symptoms are progressive with age, and correlated with osteosclerosis. The fracture frequency is increased in Type II patients, and normal in Type I, where biomechanical investigations have shown normal, or even increased trabecular bone strength. Treatment has been symptomatic. A rational treatment consists of stimulation of bone resorption, in combination with inhibition of bone formation if possible. PMID- 8358947 TI - Carbonic anhydrase II deficiency. AB - Carbonic anhydrase (CA) isoenzyme II deficiency--formerly called the syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification--is an autosomal recessive "inborn error of metabolism" that has disclosed important insight concerning osteoclast function. Nearly 50 cases have been described, predominantly from the Middle East and Mediterranean region. It is discovered late in infancy or early in childhood through developmental delay, short stature, fracture, weakness, cranial nerve compression, dental malocclusion, and/or mental subnormality. Typical radiographic features of osteopetrosis are present, and histopathologic study of the iliac crest reveals unresorbed calcified primary spongiosa. The radiographic findings are unusual, however, in that cerebral calcification appears by early childhood and the osteosclerosis and skeletal modeling defects may gradually resolve by adulthood. Patients are usually not anemic. A hyperchloremic metabolic acidosis, sometimes with hypokalemia, is caused by renal tubular acidosis that may be a proximal, distal, or combined type. Several different mutations within the CA II gene have been identified. There is no established medical therapy, and the long-term outcome remains to be characterized. Prenatal diagnosis has not been reported. Delineation of CA II deficiency establishes an important role in humans for CA II. The pathogenesis of the mental subnormality and cerebral calcification is poorly understood; however, CA II deficiency provides significant insight concerning CA II in renal regulation of acid/base homeostasis and osteoclast-mediated bone resorption. PMID- 8358948 TI - Bone densitometry observations of osteopetrosis in response to bone marrow transplantation. AB - Spinal bone density was measured in eight patients with osteopetrosis to assess the natural history of the disease and to monitor the response to therapy. Quantitative computed tomographic scans of the lumbar vertebra were obtained in seven patients, and dual photon absorptiometric scans were obtained when the technique became available. Six children were afflicted with the infantile malignant recessive condition and two with the less severe dominant condition. In all cases, bone densitometry values ranged from four to five times higher than the mean for normal age and gender-matched controls. In four children with recessive osteopetrosis, quantitative computed tomographic and dual photon absorptiometric scans showed an excellent correlation (R = 0.93) between the methods. Quantitative computed tomographic values ranged from 597 to 730 mg/cm3 (mean = 655 mg/cm3) in children with osteopetrorickets and from 901 to 1000 mg/cm3 (mean = 980 mg/cm3) in the same children when the rickets was cured. In two children treated with bone marrow transplantation, bone densitometry values returned to normal within three years. Bone densitometry provides a safe and noninvasive method for observing the natural history and therapeutic response of the osteopetrotic syndromes. PMID- 8358949 TI - Osteopetrosis. The pharmaco-physiologic basis of therapy. AB - Medical treatments of osteopetrosis have attempted to improve hematologic function, reduce the osteosclerotic condition, and/or improve immune function. Prednisone therapy has improved hematologic function in some patients, but has not resulted in a reduction in bone mass. Calcium deficient diets have limited further sclerosis in some patients. High-dose calcitriol and parathormone infusions have stimulated osteoclastic activity. In some patients, high-dose calcitriol has resulted in clinical improvement. Newer treatments, such as interferon gamma and macrophage colony stimulating factor, may alter the osteoclastic and immune defects by stimulating cellular formation and function. These therapies, alone or in combination, ameliorate but do not cure the osteopetrotic condition. PMID- 8358950 TI - Intradural recurrence with chondrosarcoma of the spine. A case report and review of the literature. AB - Known for its resistance to chemotherapy and radiation therapy, chondrosarcoma remains largely a surgically managed tumor predisposed to local recurrence and late distant metastasis. A 42-year-old man with known thoracic chondrosarcoma developed progressive low back pain, lower extremity weakness, and urinary incontinence. Magnetic resonance imaging and computed tomographic myelography demonstrated multiple filling defects throughout the lumbosacral region. Surgical excision of these lesions disclosed intradural, extramedullary drop metastases of the chondrosarcoma. The spread of neoplasms within the dural space is uncommon, accounting for less than 5% of spinal metastases, and has not previously been reported for chondrosarcoma. PMID- 8358951 TI - Anatomic relationships in the shoulder impingement syndrome. AB - Impingement syndrome of the shoulder may be produced by compression of the subacromial structures against the coracoacromial arch. The anterior tip of the acromion, the coracoacromial ligament, and the coracoid process have been implicated as sources of impingement. Anatomic specimens were examined to determine the anatomic sites on the coracoacromial arch that result in compression of the subacromial structures during specific shoulder motions that are known to produce impingement pain. The relationships of the supraspinatus tendon, the biceps tendon, and the greater tuberosity of the humerus with the coracoacromial arch were demonstrated through various arcs of shoulder motion in autopsy subjects. Biceps tendon impingement occurred predominantly against the lateral free edge of the coracoacromial ligament. Impingement of the supraspinatus tendon and greater tuberosity was demonstrated primarily against the acromial end of the coracoacromial ligament and the anterior tip of the acromion during arcs of flexion and internal rotation. The coracoacromial ligament was stretched by the greater tuberosity passing beneath it. This may explain the formation of traction osteophytes on the anterior acromion in patients with chronic impingement symptoms. PMID- 8358953 TI - Pathophysiology of perinatal asphyxia. AB - Following a severe asphyxial episode many cells can recover metabolically, and a cascade of processes are triggered in which intervention, even some hours later, can allow rescue of some cells that would otherwise die. A number of principles, however, needs to be carefully considered before extrapolating from animal to human trials. In particular, the effects on long-term outcome and on those who are compromised by intrauterine growth retardation need to be determined. It is critical to be able to identify rapidly those infants in terms of nature and severity of injury who are most likely to benefit from treatment. The dimension of time and phase of injury or recovery are key factors to effective intervention. Novel continuous cerebral function monitoring techniques such as those based on real-time spectral analysis of the EEG activity, cortical impedance monitoring, and near-infrared spectroscopy have considerable potential for determining the severity and pathophysiologic phase of injury on line. PMID- 8358952 TI - The definition of acute perinatal asphyxia. AB - Perinatal asphyxia remains a concern for physicians, patients, and attorneys. The history of concern for this condition is reviewed, and efforts in neonatal perinatal medicine to identify at risk patients and prevent serious sequelae are discussed. A definition consistent with the American Academy of Pediatrics American College of Obstetrics and Gynecology Guidelines for Perinatal Care, requiring multiple biochemical and clinical indices for asphyxia, is given. PMID- 8358954 TI - Birth asphyxia and the neonatal brain: what do we know and when do we know it? AB - In this article, the authors examine whether indicators commonly used to recognized birth asphyxia are specific to asphyxial states, and whether these allow recognition of a severity of asphyxia sufficient to pose a risk of irreversible brain injury. Characteristics recognizable within the first hours after birth are focused on because these characteristics will be of most use in clinical decisions regarding use of potential new therapies for asphyxia. PMID- 8358955 TI - Nuclear magnetic resonance imaging and spectroscopy following asphyxia. AB - Nuclear magnetic resonance imaging and spectroscopy have added significant new information about the newborn brain during and following asphyxia. NMR imaging has permitted sequential in vivo analysis of CNS maturation in the perinatal period that is superior in anatomic resolution, and especially in the characterization of myelination, to either cranial ultrasound or radiographic computed tomography. As a result, the accurate detection and recognition of the brain lesions associated with hypoxic-ischemic encephalopathy is now possible, including PVL, cerebral infarction, intraparenchymal and intraventricular hemorrhage, and delayed myelination. This has improved our understanding of the associated potential risk for abnormal neuro-developmental outcome with specific lesions. NMR spectroscopy has provided a metabolic window into the biochemical events during and following asphyxia. 31P MRS captures the phosphorous metabolites as levels rise and fall and shift in relation to each other to maintain cellular energy homeostasis in the face of oxygen depletion. Meanwhile, proton NMR spectroscopy promises to sustain the metabolic purview beyond the immediate cellular response to asphyxia to the chronic adaptation phase. Appropriately applied, this noninvasive technology may yet enable us to identify brain injury that is reversible in sufficient time to intervene and to diagnose accurately what is irreversible for timely prognostication. Furthermore, the integration of clinical imaging and spectroscopy capabilities is both feasible and desirable; information provided by each being mutually complementary. Imaging could improve spectroscopy interpretation by identifying the observed tissue, whereas MRS should clarify diagnosis of anatomic lesions detected by MRI. Advances in spatial resolution and speed of data acquisition may soon make integrated MRI/MRS a clinical reality. PMID- 8358956 TI - Near-infrared spectroscopy in asphyxial brain injury. AB - Near-infrared spectroscopy is capable of providing noninvasive quantification of several important indices of cerebral hemodynamics, including cerebral blood flow, cerebral blood volume, and its response to changing arterial carbon dioxide tension. Preliminary results in term infants following acute perinatal asphyxia suggest that cerebral blood flow and volume are elevated, and the normal control mechanisms are abolished. These hemodynamic disturbances occur prior to the later development of secondary energy failure with its poor prognosis and may allow valuable prognostic information to be obtained in the first hours after birth. PMID- 8358957 TI - Brain sonography, computed tomography, and single-photon emission computed tomography in term neonates with perinatal asphyxia. AB - The clinical diagnosis of hypoxic-ischemic brain injury in neonates can be supported by radiologic studies including cranial sonography, computed tomography (CT), single-photon emission computed tomography (SPECT), magnetic resonance imaging, and positron emission tomography. The role of cranial sonography, CT, and SPECT in term neonates with perinatal asphyxia is reviewed in this article. PMID- 8358958 TI - Positron emission tomography scanning: applications in newborns. AB - Positron emission tomography (PET) is an imaging technique that allows local chemical and physiologic functions in various body organs to be measured. Studies of local cerebral glucose metabolism in infants and children using PET have provided important information on human brain functional development and plasticity. In the neonate, PET studies have provided important clues into the pathophysiology of hypoxic-ischemic injury. Patterns of cerebral glucose utilization in various clinical subtypes of cerebral palsy associated with perinatal brain injury are discussed and contrasted to metabolic patterns seen in cerebral palsy without clear etiology. Expanding PET technology provides a new approach that holds great promise in the diagnosis and management of brain disorders affecting the neonate. PMID- 8358959 TI - Perinatal asphyxia: effects of biologic and environmental risks. AB - The literature on biologic risks, such as asphyxia, and later outcome contains many confounding issues. Earlier data may not be applicable today because of high mortality rates and significant changes in medical practice. Data from a more contemporary cohort indicate an association between arrays of biologic variables and outcome, although early developmental/behavioral measures are more predictive. Some variables had a 'sleeper effect,' which did not surface until 36 months. Suggestions for better delineation of relationships between nonoptimal risk variables and outcome are provided. PMID- 8358960 TI - Visual-evoked potentials in neonates following asphyxia. AB - Visual evoked potentials (VEPs) are easily recorded in the neonatal intensive care setting using light-emitting diode goggles as the flash stimulus. They are sensitive measures of CNS integrity and are altered or abolished by hypoxia. Prognosis in newborns with birth asphyxia or hypoxia is difficult to predict; however, the VEPs have been shown to be very helpful. Absent VEPs carry a poor prognosis; persistently abnormal, i.e., beyond 1 week, also predict abnormal outcome. Normal VEPs by 1 week have an accuracy rate around 90% for normal outcome. PMID- 8358961 TI - Somatosensory-evoked potentials in term neonates with postasphyxial encephalopathy. AB - This article reviews the use of median nerve somatosensory-evoked potentials in full-term neonates with postasphyxial encephalopathy. The predictive value of this technique with regard to neurodevelopmental outcome is compared with that of clinical assessment and cranial ultrasonography. PMID- 8358962 TI - Recent advances in the genetics of heritable breast cancer. PMID- 8358963 TI - Expression of the pS2 peptide in normal human glandular endometrium during the menstrual cycle: a possible function. PMID- 8358964 TI - HLA-DPA1 and HLA-DPB1 in rheumatoid arthritis and its subsets. AB - The aim of this study was to examine the relationship between HLA-DP and susceptibility to articular and extra-articular features (Felty's syndrome and vasculitis) of rheumatoid arthritis (RA). The possible association of DP types with severity of articular disease was also analysed. No statistically significant associations were observed between HLA-DP alleles and articular or extra-articular features of RA, or to the severity of the arthritis when p was corrected for the number of alleles tested. PMID- 8358965 TI - An assessment of the clinical usefulness of two serum markers, CA15 3 and HMFG 2 in localized and metastatic breast cancer. AB - CA 15 3 is a circulating glycoprotein defined by two monoclonal antibodies (115 D 8 and DF 3) with good specificity for breast cancer. Tumour-associated antigens have been detected by the monoclonal antibody HMFG 2 using a low pH ELISA method. We compare the values obtained using these two assays in patients with localized and metastatic breast cancer. CA 15 3 and HMFG 2 levels were measured in 61 patients, 24 localized and 37 metastatic, evaluated by standard biochemical and radiological testing. Of the patients with metastatic disease 78.4 per cent had an elevated CA 15 3 level whereas only 8.3 per cent of patients with localized disease had an elevated level (chi 2 = 28.2 p = 0.001); 29.8 per cent of patients with metastatic disease had elevated HMFG 2 levels while among those with localized disease 16.7 per cent had elevated levels (chi 2 = 0.57 p = NS). We conclude that only CA 15 3 is a useful marker in advanced disease. PMID- 8358966 TI - Economic credentialing: can physicians and hospitals find common ground? PMID- 8358967 TI - Colorado Society of Internal Medicine. Survey of Colorado's internists completed. PMID- 8358968 TI - People-to-People (thoracic and cardiovascular surgeons) visit Viet Nam and Southeast Asia. PMID- 8358969 TI - Confidential medical care important to adolescents. PMID- 8358970 TI - Vertical integration: what is it and what does it mean for physicians? PMID- 8358971 TI - Thyroid disorders in patients with progressive systemic sclerosis: a review. PMID- 8358972 TI - Histopathology of the vessels of the femoral heads in specimens of osteonecrosis, osteoarthritis and algodystrophy. AB - The authors studied by light microscopy the vessels of the femoral head and neck in 38 well preserved specimens from core biopsy. There were 17 cases of osteonecrosis (ON), 11 cases of osteoarthrosis (OA) and 10 cases of reflex sympathetic dystrophy, so called algodystrophy (AD). Mean age of the patients was respectively 44, 45 and 42 years. The sex ratio, M/F, was respectively 12/5, 6/5 and 9/1. Types of staining used were hematoxylin-eosin, Masson Trichrome, P.A.S. and Verhoeff. In counting, thick-walled and thin-walled vessels were distinguished. There was a significant reduction in the number of the thick- and thin-walled vessels, in the ON group, by comparison with the OA and AD groups. An increased number of thin-walled vessels in the AD group were also observed. Morphological study showed an abnormal frequency of fibrosis of the media in the arteries of the ON group, i.e. arteriosclerosis. These data were compared with the few other histopathological studies previously published. The authors recommend further studies in order to precise their frequency and their significance. PMID- 8358973 TI - Electrophoretic separation of alkaline phosphatase isoenzymes in synovial fluid and serum from patients with rheumatoid arthritis. AB - The alkaline phosphatase enzyme in both serum and synovial fluid from 28 cases of rheumatoid arthritis and from the serum of 30 controls was measured. The enzyme was further studied by separating its isoenzymes to clarify their origin in both synovial fluid and serum of 10 patients with elevated level of the enzyme in their sera. The level of the enzyme in serum was elevated in 37% of patients confirming previous reports on that point. The most abundant isoenzyme in the synovial fluid (66.9%) was found to be bone in origin while in serum the most abundant isoenzyme was found to be hepatic (60.5%). This may be responsible for increased bone turn-over in rheumatoid joints whether in formation or resorption. PMID- 8358975 TI - Validity of echographic evaluation of cartilage in gonarthrosis. Preliminary report. AB - We studied an echographic technique by which precise reproducible measurements of articular cartilage thickness of the knee is possible. Two groups of individuals were studied: a group of 18 patients with gonarthrosis and a control group of 10 normal individuals. The group of 18 patients with gonarthrosis was studied by ultrasound (US) before knee prosthesis surgery. The cartilage thickness was measured within the weight-bearing area. US re-evaluation and histological measurements were made on the pathological specimen following the operation. Results of pre- and post-operative US data were compared with histological data. A good correlation between these measurements was found [P(t) > 10%]. In order to have comparative reference values of the articular cartilage within the weight bearing area of the femoral trochlea a group of 10 control subjects was also studied with US as above. We found that the articular cartilage thickness of the femoral trochlea in the weight-bearing area has a mean of 2.2 +/- 0.3 mm for the lateral condyle and 2.3 +/- 0.2 mm for the medial condyle. The intra-observer and inter-observer difference in measurements was evaluated with Student's t-test. Our data demonstrate that US measurements of articular cartilage thickness of femoral condyles is a sensitive and reproducible technique which permits early diagnosis and management of knee arthropathy as well as quantification of cartilage damage. PMID- 8358974 TI - Proprioceptive sensibility in women with normal and osteoarthritic knee joints. AB - The objective of this study was to quantify the effect of degenerative joint change on the proprioceptive acuity of women with osteoarthritis (OA) of the knee. Middle-aged women with OA of the knee, age-matched healthy women, and younger healthy women were studied. Tests examined the ability of subjects to correctly reproduce knee angles in weightbearing and non-weightbearing situations. The knee angles were photographed and measured in degrees. The absolute error (AE) of each matching test was calculated and the mean AE of two tests was used as the criterion variable in a three-way analysis of variance (ANOVA). The relationship between the reproduction error and the osteoarthritic subjects' self-paced walking speed was also examined. Under both test conditions the AE of the osteoarthritic subjects was greater than that of the healthy subjects (p < .05). There was, however, no significant relationship between the AE measurements of the patients and their walking speed. These data indicate that while women with OA may have poorer proprioception than healthy controls, this impairment may not affect their walking ability. PMID- 8358976 TI - Effect of zopiclone on sleep quality, morning stiffness, widespread tenderness and pain and general discomfort in primary fibromyalgia patients. A double-blind randomized trial. AB - Thirty-three patients fulfilling the diagnostic criteria for primary fibromyalgia completed an eight-week double-blind treatment trial with the drug zopiclone. Of outcome measures studied a score expressing subjective sleep quality showed improvement in more than ninety percent of zopiclone patients at 4 weeks and nearly eighty percent at 8 weeks, but similar improvement was also reported by more than sixty percent of the patients on placebo. Patient self-assessment of a treatment effect also showed an advantage for zopiclone, with most patients in the placebo group considering their state as unchanged at 8 weeks. According to examiner assessment, however, half the patients in both groups showed improvement at 8 weeks. For other assessment variables, e.g. dolorimeter assessment of widespread tenderness, visual analogue scales and pain drawings for pain and other subjective feelings of discomfort, the effects of zopiclone treatment were at the same level as those of placebo. PMID- 8358977 TI - Skeletal manifestations of moderate phosphate diabetes. AB - Six patients, with vertebral osteoporosis and reflex sympathetic algodystrophy syndrome of the lower limbs, due to moderate diabetes, are presented. Osteoporosis was documented by low CT scan bone density and moderate decrease of bone trabecular volume. Histomorphometric studies found a mild increase of resorption areas. All patients had unremarkable serum phosphorus level (mean: 0.91 +/- 0.13) but increase of urinary phosphorus excretion was documented by phosphate clearance higher than 20ml/mm, phosphate tubular reabsorption lower than 80% and TmPo4/GFR lower than 0.8mmol/l. Phosphate clearance and phosphate tubular reabsorption are studied in two control groups. Mild phosphate diabetes, of unknown incidence and prevalence (need for prospective studies) may be the vector of osteoporosis, vertebral and peripheral. The diagnosis of PD requires determination of phosphate clearance, phosphate tubular reabsorption, TmPo4/GFR and these tests may be useful in the diagnostic work up of bone demineralization disorders. We thought that osteoporosis could be the result of progressive dissolution of bone apatite crystals necessary to maintain normal or sub-normal blood phosphate level in spite of the phosphate diabetes. PMID- 8358978 TI - Rheumatoid arthritis as a cause of cardiac compression. Favourable long-term outcome of pericardiectomy. AB - In order to clarify the significance of rheumatoid arthritis (RA) as a cause of cardiac compression, we scrutinized pericardiectomy files of 47 patients over a ten-year period at two university hospitals in Finland. Five patients with RA were found. All the patients with RA were men with seropositive disease and subcutaneous rheumatoid nodules. Two of the patients had pulmonary fibrosis, one had cutaneous vasculitis and three had had rheumatoid pleurisy. There was a mean delay of 10 months from the first cardiac symptom to the diagnosis of cardiac compression, the most common misdiagnosis being primarily a liver disease. On the basis of clinical and operative data, four out of the five patients had constrictive pericarditis and one had an effusive-constrictive form of the disease. The histopathological findings in all cases were consistent with chronic fibrosing pericarditis. A follow-up of seven to seventeen years of four patients has not revealed any signs of recurrent pericardial disease. Our results demonstrate that RA is an important aetiological factor for cardiac compression. The long-term outcome of this manifestation seems to be good after pericardiectomy. PMID- 8358979 TI - Increased soluble IL-2 receptor in serum of patients with systemic lupus erythematosus. AB - We estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer. PMID- 8358980 TI - Better effect of methotrexate on C-reactive protein during daily compared to weekly treatment in rheumatoid arthritis. AB - Treatment with methotrexate (MTX) is well established in rheumatoid arthritis (RA), but dosing remains arbitrary as studies on the effect of different dosing schedules are lacking. In a randomised crossover design of 20 patients with RA, the effect of low (2.5mg) oral daily doses of MTX (15 mg weekly) was compared to intermittent weekly dosing (15 mg). C-reactive protein (CRP) values were lower and more stable on daily dosing compared to the significant (p < 0.05) changes in CRP observed during treatment with the same weekly dose. It may be postulated that nonresponders or patients with dose-dependent side effects may have clinical advantage from daily MTX dosing if hepatotoxicity and other side effects are not increased. PMID- 8358981 TI - Echocardiographic findings in patients with primary Sjogren's syndrome. AB - Cardiac involvement in 27 consecutive patients fulfilling the criteria for primary Sjogren's syndrome was evaluated using echo-doppler-cardiography. A clinical physical examination showed that the heart was normal in all patients. Nine (33%) had signs of present or previous pericarditis with effusion and/or fibrin deposition, four of them had chest symptoms. The pericarditis patients were slightly older, had significantly shorter disease duration, had significantly increased levels of orosomucoid and haptoglobin, and were significantly more often antinuclear-antibody positive than those without pericarditis. Of the echocardiographic measurements, the left ventricular systolic dimension was significantly smaller and the fractional shortening of the left ventricle significantly higher in the pericarditis patients. However, four of the nine pericarditis patients had localized hypokinesia of the left ventricle, all with unspecific ECG changes, while only one without pericarditis showed this symptom. No patient had low voltage, ST-T elevation or conduction abnormalities. Mitral valvular thickening was found in one patient and age related sclerosis of the aortic cusps appeared in some. PMID- 8358982 TI - Liver involvement in giant cell arteritis. AB - Giant cell arteritis is a vasculitis which usually affects large and medium-sized vessels in patients over 50 years old. The liver is one of the internal organs which can be involved in this systemic disease. During the last 15 years, 56 patients with giant cell arteritis were seen in our hospital. In 12 patients disturbed liver function test were found. In the majority of cases the disturbance was of cholestatic type and resolved completely with steroid treatment. The association of temporal arteritis with disturbed liver function tests is discussed, with a review of the recent literature. PMID- 8358983 TI - Intestinal absorption in patients with rheumatoid arthritis treated with methotrexate. AB - Twelve patients with rheumatoid arthritis treated for at least 12 months with methotrexate and 11 matched rheumatoid arthritis controls underwent a standard d xylose absorption test. No patients had any pre-existing clinical of biochemical evidence of malabsorption. No significant difference was observed in the 1 hour plasma d-xylose estimation between methotrexate treated patients and controls. The 2 to 5 hour urinary excretion ratio, however, was significantly lower in the methotrexate-treated group compared with controls indicating a minor degree of malabsorption. Six of the methotrexate treated patients and 5 of the controls underwent endoscopic duodenal biopsy but neither group demonstrated any significant histological changes. In conclusion, methotrexate therapy in patients with rheumatoid arthritis produces mild intestinal malabsorption. PMID- 8358984 TI - Free plasma concentrations of piroxicam in patients with osteoarthritis: relation to age, sex and efficacy. AB - Steady state piroxicam plasma samples from 85 patients suffering from osteoarthritis of the hip and/or the knee, and treated with piroxicam 20 mg daily for at least four weeks, were obtained. Twenty-seven of these patients had a newly diagnosed osteoarthritis and had not been treated with a nonsteroidal antiinflammatory drug (NSAID) previously. The plasma samples were subjected to equilibrium dialysis, analyzed by HPLC and total and free drug concentrations measured and unbound fractions were calculated. In the 27 newly diagnosed patients with free piroxicam concentrations ranging from 0.004 to 0.117 micrograms/ml, there was no correlation between free concentration and change in any of the clinical response variables from pretrial to week 4. In the total patient population free concentrations were 0.057 +/- 0.038 micrograms/ml (mean +/- standard deviation). Females had a 79% higher free concentration than males (p < 0.0002) and there was a statistically significant (p < 0.01) increase of free concentration with increasing age in females. The unbound fraction was 0.87% +/- 0.36% (mean +/- SD). There was no difference in unbound fraction between the sexes, nor could we detect any change with increasing age. PMID- 8358985 TI - Plasma concentration of human atrial natriuretic hormone in patients with connective tissue diseases. AB - Atrial natriuretic peptide (ANP), a peptide released from the cardiac atria, compensates blood volume expansion by its diuretic, natriuretic and vasoactive properties. We measured human plasma ANP(hANP) levels in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and progressive systemic sclerosis (PSS) and found that their values were higher than those of healthy controls. In SLE patients, hANP levels correlated with serum creatinine concentration and the patients with proteinuria showed high levels of hANP. Administration of large amount of corticosteroid as a remission induction of the patients with SLE caused high levels of hANP. In patients with PSS, %FEV1 showed strong inverse correlations between hANP levels, and the patients with an enlarged second curvature of the heart had high levels of hANP. In patients with RA, no significant correlation was found between hANP levels and clinical variables including patients' age. PMID- 8358986 TI - Lumbar bone mineral density in anorexia nervosa. AB - We studied lumbar bone mineral densities (BMD) using a dual photon absorptiometer in 18 women with anorexia nervosa (AN). Results were compared with data from a control group of 36 healthy women. We found significantly reduced mean bone densities as compared with control group (0.814 +/- 0.072 g/cm2 hydroxy-apatite equivalent vs 1.011 +/- 0.023; p < 0.01). Only one patient developed vertebral compression fracture. BMD was negatively correlated with duration of amenorrhoea (r = -0.68; p < 0.01) but not significantly with duration of AN. We found no correlation between BMD and estradiol blood levels, age of onset, body mass index and daily calorie intake. The correlation between BMD and duration of amenorrhoea may indicate that long standing estrogen deficiency is a major factor in the osteoporosis (OP) observed in AN. PMID- 8358987 TI - Increased levels of urinary collagen crosslinks in females with rheumatoid arthritis. AB - Bone loss is a feature of RA, but the exact mechanisms involved are not clear. The collagen crosslinks deoxypyridinoline (DPYR) and pyridinoline (PYR) are specific indices of 'mature' collagen breakdown and reflect increased bone turnover. The aims of the study were to examine crosslink levels in RA and their association with disease activity and the effect of steroids. Urinary crosslinks corrected for creatinine were measured on morning fasting samples by HPLC in 70 postmenopausal women with rheumatoid arthritis (RA) aged 45-65 and compared with 169 postmenopausal healthy age-matched controls from the population. Mean levels of PYR were significantly higher in RA cases than in controls (52.4 versus 37.5 nmols/mmolCr) although mean levels of DPYR did not differ significantly. A weak correlation was found with ESR and PYR (r = 0.35) but not with other markers of disease activity. Thirteen of the RA cases were current steroid users and their levels of DPYR and PYR even with low doses, were significantly elevated above those of non-users, ex-users and controls. The finding of raised urinary PYR but not the bone specific DPYR in nonsteroid using RA cases suggests that the increased collagen breakdown does not primarily come from bone but from other sources such as cartilage and synovium. The large increases in collagen excretion in low dose steroid users, may reflect the higher risk of osteoporosis in this group. PMID- 8358988 TI - The value of specific antibody detection and culture in the diagnosis of reactive arthritis. AB - Joint inflammation, predominantly of the lower limbs, occurring some weeks after urogenital or gastrointestinal infection is classified as reactive arthritis (ReA) but there is no general agreement on diagnostic criteria, especially if the preceding infections are asymptomatic. The same is true for Lyme disease (LD) which is caused by Borrelia burgdorferi (BB). Determination of antibody titre or culture of urethral swabs and stools are often used as diagnostic tools. We examined 4 groups of patients: one with undifferentiated arthritis (Group I, n = 55), one with well-defined rheumatic diseases other than ReA (n = 43, Group II), one group without joint disease (n = 50, Group III) and one with ReA or LD (n = 7). Specific antibacterial antibody titres in serum were measured in all patients; stool and urethral cultures were performed in all groups except the last. A calculation of positive predictive value (PPV) was done for each test. Evidence of present or previous infection with the microbes Chlamydia trachomatis (CT), Mycoplasma urethritidis (MU), Yersinia enterocolitica (YE) and BB were found in all groups. In Group I, Group II and Group III respectively, positive serological results were found for CT IgA (20%, 31%, 16%) and IgG (49%, 51%, 34%), YE (7%, 6%, 0%) and BB (17%, 2%, 10%). Positive cultures were found in Group I and Group II respectively for CT (28%, 29%) and MU (14%, 17%). Therefore no test had a significant positive predictive value for ReA in the general population and even in the rheumatology clinic the PPV for most tests was low. We conclude that these methods are of little value in the diagnosis of reactive arthritis when the preceding infection is asymptomatic. PMID- 8358989 TI - Sneddon's syndrome and phospholipid antibodies. AB - We present a case of Sneddon's syndrome with high titers of antiphospholipid antibodies (APLA), in which the leading symptom was an incapacitating memory defect. MRI revealed vasculitic lesions of the central nervous system (CNS). Therefore immunosuppressive therapy was started with steroids and cyclophosphamide pulses. The transient beneficial effects of such a therapy will be discussed. PMID- 8358990 TI - A case of Sjogren's syndrome complicating immune-mediated aplastic anaemia. AB - A 78-year-old Japanese woman with Sjogren's syndrome complicating immune-mediated aplastic anaemia is described. A diagnosis of aplastic anaemia was made from severe pancytopenia with hypoplastic marrow. Laboratory studies suggested an association of bone marrow suppressive T-lymphocytes with the pathogenesis of aplastic anaemia. Following the administration of mepithiostan and prednisolone, pancytopenia improved gradually. Two years after the onset of aplastic anaemia, Raynaud's phenomenon developed and examinations revealed the existence of keratoconjunctivitis sicca and anti-SSA/Ro and anti-SSB/La antibodies. PMID- 8358991 TI - Astasia-abasia revealing a primary Sjogren's syndrome. AB - A 63-year-old woman presented with mild arthralgias and inability to stand and walk without other significant neuropsychiatric abnormality. Neurological explorations showed intrathecal oligoclonal immunoglobulin production in CSF and numerous bright foci at brain MRI. A primary Sjogren's syndrome was concomitantly evidenced and was thought to be the cause of the astasia-abasia symptom by multiple brain involvement. Patient's condition gradually improved with hydroxychloroquine and corticosteroid therapy. Central nervous system involvement by primary Sjogren's syndrome is discussed. PMID- 8358992 TI - Ankylosing spondylitis in two Zairian brothers. AB - Ankylosing spondylitis has never been described in Zaire and is considered to be rare in black African populations. We report two cases observed in the University Hospital of Kinshasa. The two patients are brothers. The diagnosis is based on anaemnestic, clinical and radiological findings. We therefore demonstrate the existence of this disease in Zaire and presume that other similar cases may be diagnosed. PMID- 8358993 TI - Seronegative spondyloarthropathy associated with megarectum. AB - In this report we describe a case of a 19-year-old man with a two-year history of polyarthritis affecting the lower limbs and dactylitis of the toes. His clinical picture fulfilled the new European diagnostic criteria for spondyloarthropathies. Systemic examination revealed a big mass in the left iliac fossa that was found to be due to an acquired functional megacolon. Complete remission of the joint involvement was obtained by treating the bowel disease. PMID- 8358994 TI - Chronic destructive monoarthritis of the wrist in patients with anti-SSA/Ro antibodies: report of two cases. AB - Among 340 patients with rheumatic diseases, two cases of chronic destructive monoarthritis of the wrist with anti-SSA/Ro antibodies and rheumatoid factor, were observed for over three years. It is not clear whether these cases represent a specific subset of rheumatoid arthritis (RA) or whether they may progress to diffuse symmetrical destructive polyarthritis typical of RA. Long-term follow-up studies including analysis of autoantibodies will be needed to clarify the characteristics and course of chronic monoarthritis. PMID- 8358995 TI - A case of scurvy presenting with cutaneous and articular signs. AB - This report is on a patient, who presented purpura and hemarthrosis in a context of vitamin C deficiency. This case gives us the opportunity to discuss the differential diagnosis, the clinical features, the pathogenicity and the treatment of this rare condition. PMID- 8358996 TI - Paraneoplastic Raynaud's phenomenon. AB - A testicular tumour could be diagnosed by the occurrence of a Raynaud's phenomenon complicated by severe digital arteritis. The arteritis rapidly regressed under prostacyclin therapy. Such vascular manifestations are frequent in testicular carcinoma, but they usually develop after chemotherapy. To our knowledge, this is the first case where they preceded the diagnosis and specific treatment of a tumour of the testis. PMID- 8358997 TI - Is the benign joint hypermobility syndrome benign? PMID- 8358998 TI - Fatal outcome of low-dose methotrexate therapy in rheumatoid arthritis. PMID- 8358999 TI - Interleukin-2 production in early rheumatoid arthritis. PMID- 8359000 TI - Epidemiologic typing of multiply drug-resistant Pseudomonas aeruginosa isolated from an outbreak in an intensive care unit. AB - From June to August 1991, there was an outbreak of Pseudomonas aeruginosa infections in an intensive care unit in a general hospital in Sao Paulo, Brazil. We obtained 14 isolates from 14 patients, 11 from tracheal aspirate, and 3 from surgical wound exudates. These strains were typed by serotyping, pyocin typing, and pulsed-field electrophoresis (CHEF) of chromosomal DNA (chrDNA), and the different typing methods were analyzed. These three methods demonstrated seven identical strains. We also performed an extensive antibiogram (33 drugs) in all 14 isolates. The incidence of resistance to aminoglycosides, extended-spectrum beta-lactams, and quinolones was very high among the seven identical isolates; however, the antibiogram profile differed significantly among the isolates. Our results suggest that a unique strain caused several cross-transmitted infections during this period of time, and the emergence of antimicrobial resistance has been occurring before and after the establishment of the epidemic strain by selective drug use. The chrDNA fingerprinting proved to be versatile and precise for epidemiologic investigations of P. aeruginosa infections. PMID- 8359001 TI - Clinical assessment of anaerobic isolates from blood cultures. AB - Patients at two tertiary-care medical centers were evaluated to determine the clinical significance of anaerobic isolates from their blood specimens and to identify whether aerobic and/or anaerobic conditions were necessary for the detection of Streptococcus pneumoniae isolates. Significant anaerobes were isolated from only 0.1% and 0.4% of all blood cultures collected. The majority of patients with significant anaerobes had clinical conditions in which anaerobes are known to cause infections. Of the S. pneumoniae organisms, 83% were isolated only from the aerobic bottles of a blood culture set. These data lend support to the recommendations for the selective ordering of anaerobic blood cultures without compromising the isolation of S. pneumoniae. PMID- 8359002 TI - Identification of clinical isolates of nondiphtherial Corynebacterium species and their antibiotic susceptibility patterns. AB - Starting in 1982, our laboratory has performed species identification of coryneform bacteria isolated from blood cultures, intravenous (i.v.) catheter tips and sites, urines with high colony counts, and other potentially significant cultures, using predefined criteria. Of 283 isolates identified, Corynebacterium jeikeium was the most common (47%), followed by CDC group G2 (12%) and C. minutissimum (8%). Blood cultures and i.v. catheter-related sources were the most frequent sources (58% of total). Certain species or groups, like CDC group G2, were most frequently isolated from blood or i.v. catheter sites. CDC group G2 showed a progression to greater multiple antibiotic resistance during this 9-year period. Occasional multiresistant strains of other species were also encountered. By in vitro testing, we note vancomycin remains the most active agent against corynebacterialike organisms, and is the most reliable antibiotic to use while awaiting susceptibility testing results. PMID- 8359003 TI - Application of a leukocyte and nitrite urine test strip to the management of children with neurogenic bladder. AB - A urine leukocyte count of > or = 50/mm3 together with a bacterial count of > or = 10(5) colony-forming units (CFUs) per milliliter was used to define significant infection in 160 children with neurogenic bladder and evaluate the leukocyte and nitrite components of the Chemstrip 9 test. A Chemstrip 9 leukocyte reading of < or = 25 together with a negative nitrite reaction occurred in 99 children and had a sensitivity of 83.5% and a negative predictive value for infection of 97.0%. A Chemstrip 9 reading of > or = 500 leukocytes together with a positive nitrite reaction occurred in 18 children and had a sensitivity of 40% with a 100% positive predictive value for infection. Other combinations of Chemstrip 9 leukocyte and nitrite reactions were unhelpful or of uncertain value. Selection of up to three specimens from each patient increased the number of samples to 360 and provided general confirmation of the above conclusions. Nitrofurantoin may reduce the sensitivity of the nitrite strip reaction. PMID- 8359004 TI - Posthysterectomy wound infection. A review. AB - We reviewed the microorganisms isolated from gynecologic surgery wounds showing signs of infection, from January to December 1990. A total of 88 samples of abdominal wall exudates from as many patients who had undergone abdominal hysterectomy were studied. In 54 women (61.3%), cultures were positive and, in 26 specimens (48.1%), mixed aerobic-anaerobic flora were isolated. In 28 cases (51.9%), a single microorganism was isolated, the most frequent being Staphylococcus aureus, followed by Mycoplasma hominis and Escherichia coli. Mycoplasma hominis was unexpectedly frequent, appearing in five women with wall abscess and fever. PMID- 8359005 TI - In vitro antimicrobial activity of tioconazole and its concentrations in vaginal fluids following topical (vagistat-1 6.5%) application. AB - In vitro assays demonstrated that clinical yeasts were significantly more inhibited by tioconazole (MIC50, < or = 0.5 microgram/ml) than by fluconazole (MIC50, 8 micrograms/ml). Tioconazole also exhibited high potency against most molds (Alterneria spp. and Acremonium spp.). All Candida tropicalis isolates had MICs of 8 micrograms/ml, four-fold greater than any other Candida spp. Generally Gram-negative bacteria were less susceptible to tioconazole. Moraxella catarrhalis (MIC90, 2 micrograms/ml) was the most susceptible Gram-negative species. Staphylococci and enterococci were the most susceptible to tioconazole Gram-positive species (MIC50s, 1-8 micrograms/ml). Bacterial species associated with vaginosis. [Gardnerella vaginalis (MIC90, 16 micrograms/ml), Mobiluncus spp. (MIC90, 16 micrograms/ml) and Prevotella biviadisiens (MIC90, 64 micrograms/ml)] were inhibited by tioconazole. Isolates of Lactobacillus spp. were most resistant (MIC90, > or = 256 micrograms/ml) to tioconazole. Vaginal fluid levels of tioconazole (mean, 91.4 micrograms/ml) persisted above the MIC90 levels (1-64 micrograms/ml) for most fungal and bacterial pathogens for 72 h in 19 evaluable female human subjects receiving 300 mg tioconazole in an intravaginal ointment. PMID- 8359006 TI - Sensitivity of surveillance cultures for the detection of methicillin-resistant Staphylococcus aureus in a nursing-home-care unit. AB - This study compared the sensitivity of nasal culture alone versus multiple-site cultures and single versus duplicate sampling for the detection of methicillin resistant Staphylococcus aureus (MRSA)-colonized individuals in a nursing-home population. Repeat culture of 68 specimens collected from 35 colonized subjects yielded identical results for 57 specimens, (84%), and 89% of the colonized residents (31 of 35) were identified by the first culture of multiple sites. A single nares culture detected 27 (77%) of 35 (first screen) and 29 (83%) of 35 (second screen) residents colonized with MRSA at any site. The most cost effective screening would consist of a nasal culture only or combined with a gastrostomy tube site, if applicable. To identify all colonized individuals, however, it would be necessary to culture more than one specimen from multiple sites on each resident. PMID- 8359007 TI - An enzyme immunoassay for the direct detection of adenovirus in clinical specimens. AB - A total of 414 clinical samples were tested by an enzyme immunoassay (EIA) for direct detection of adenovirus as well as cultured in Graham 293, A549, and human diploid foreskin fibroblast cells. Adenovirus was detected in 69 (16.7%) of 414 clinical specimens. The EIA detected adenovirus in 51 (12.3%) of 414 specimens; two were EIA positive only. Adenovirus was isolated from 67 (16.2%) of 414 specimens; 18 were culture positive only. Compared with viral isolation, EIA had a sensitivity of 73.4% and a specificity of 99.4%, with a positive predictive value of 96% and a negative predictive value of 95%. PMID- 8359008 TI - In vitro susceptibility test practices with Haemophilus influenzae among College of American Pathologists survey participants in the United States. AB - Questionnaire results from 5233 clinical microbiology laboratories participating in the College of American Pathologists (CAP) survey program in the United States were used to establish current standards of practice with respect to in vitro susceptibility testing of Haemophilus influenzae. The results of this CAP survey indicated that the recently developed National Committee for Clinical Laboratory Standards (NCCLS) guidelines for H. influenzae susceptibility tests have been widely adopted, particularly with regard to the medium used to perform susceptibility tests. Haemophilus test medium (HTM) is now the most commonly used medium and there exists a general level of satisfaction (approximately 80%) with medium performance. Specific methodologic recommendations of the NCCLS, however, are often not being followed, for example, length and atmosphere of incubation and means of preparing inocula. beta-Lactamase assays constitute a very commonly employed means of assessing ampicillin activity. Among susceptibility test methods, disk diffusion (82.2%) is much more commonly used compared with broth microdilution (17.8%) procedures. Data are provided regarding the most commonly tested antimicrobials as well as some of the problems encounted when using current NCCLS methods for susceptibility tests with H. influenzae. Finally, the CAP survey questionnaire revealed that many laboratories have applied HTM to susceptibility tests with other fastidious bacteria such as pathogenic Neisseria sp., streptococci, and Moraxella catarrhalis. PMID- 8359009 TI - Evaluation of disk susceptibility testing of fosfomycin tromethamine. AB - Fosfomycin tromethamine is an orally administered fosfomycin that may be used for single-dose therapy of uncomplicated urinary tract infections. At breakpoint concentrations [< or = 128 micrograms/ml plus 25 micrograms/ml glucose-6 phosphate (G-6-P)], fosfomycin tromethamine inhibited > 90% of the 350 bacterial isolates tested. When testing Escherichia coli, Klebsiella spp., and Enterobacter spp., we note that the performance of fosfomycin disks improved when G-6-P was added to the disks. The interpretive error rates were minimized when 200 micrograms fosfomycin disks were supplemented with either 50 or 100 micrograms G 6-P. Using < or = 128 and > or = 256 micrograms/ml as the susceptible and resistant MIC breakpoints, respectively, the regression-analysis-derived disk diffusion zone diameter breakpoints for the 200-micrograms fosfomycin disk supplemented with 50 micrograms of G-6-P are as follows: susceptible, > or = 16 mm; intermediate, 13-15 mm; and resistant, < or = 12 mm. PMID- 8359010 TI - Comparison of vidas Clostridium difficile toxin-A assay and premier C. difficile toxin-A assay to cytotoxin-B tissue culture assay for the detection of toxins of C. difficile. AB - Damage to the intestinal mucosa by Clostridium difficile (CD) is toxin mediated. Two enzyme immunoassays (EIAs) for toxin-A detection, the automated Vitek immunodiagnostic assay system CDA (Vidas CDA), and the Premier toxin A (Premier) were tested for their ability to detect toxin A in 301 stool samples and compared with an in-house tissue culture assay for toxin B (TCA). Of these 301 samples, 49 were TCA positive and 252 were TCA negative. Agreement between Vidas CDA and TCA on the initial run was 85% (255 of 301) and increased to 94% (278 of 296) when discordant samples were retested from available frozen specimens. Corresponding levels of agreement for Premier were 91% (272 of 301) and 98% (284 of 288), respectively. If tissue culture positivity at any titer was used as the sole criterion for positivity of the specimen, agreement with positive TCA before and after repeat testing was 57% (26 of 49) and 74% (34 of 46) for Vidas CDA and 65% (32 of 49) and 95% (36 of 38) for Premier. Agreement with negative TCA titers was good: 90% for Vidas CDA and 95% for Premier, and 98% for Vidas CDA and 99% for Premier after repeat testing. Predictive values positive and negative after repeat testing were, respectively, 88% and 96% for Vidas CDA, and 95% and 99% for Premier. Results for the automated and manual EIA methods for detection of C. difficile toxin A were obtained in 2.5 h as compared with 36-48 h for tissue culture. PMID- 8359011 TI - A comparison of the in vitro postantibiotic effect of meropenem and imipenem versus selected enterobacteriaceae and other pathogens. AB - The in vitro postantibiotic effect (PAE) of meropenem (Merrem or SM-7338) and imipenem was determined by using 12 strains of clinically important pathogens. A PAE of > or = 1/2 h duration was observed more frequently with strains tested against meropenem than with imipenem. PMID- 8359012 TI - In vitro antimicrobial activity of CP-99433 compared with other fluoroquinolones. AB - CP-99433 is a new C-7 diazabicyclofluoroquinolone with a broad spectrum of activity that includes Enterobacteriaceae, Gram-positive cocci, and nonenteric Gram-negative bacilli. Potent activity was demonstrated against Pseudomonas aeruginosa [minimum inhibitory concentration (MIC90, 0.5 microgram/ml), Xanthomonas maltophilia (MIC90, 1 microgram/ml), and all Streptococcus species (MIC90s, 0.25-1 microgram/ml). Only CP-99433 was active against Enterococcus faecium (MIC50, 2 micrograms/ml). CP-99433 also demonstrated activity against several ciprofloxacin-resistant staphylococci. Additional studies of CP-99433 activity appear indicated. PMID- 8359013 TI - The biological basis of ethanol tolerance in Drosophila. PMID- 8359014 TI - Muscle actin genes in insects. PMID- 8359015 TI - Changes in ketone body utilization by chick liver, duodenal mucosa and kidney during embryonic and postnatal development. AB - 1. Lipid synthesis from acetoacetate and 3-hydroxybutyrate in chick kidney and duodenal mucosa showed a clear decrease between 15 and 19 days of the embryonic phase, followed by an increase at hatching and a new decrease during the first neonatal period. The hepatic synthesis of lipids presented a different profile: a peak at 19-day-old embryo and a new increase during postnatal development. 2. These changes would be related to those in 3-hydroxybutyrate concentration in chick plasma throughout the perinatal period. 3. Phospholipids were the main kind of lipid formed in the three tissues. An appreciable percentage of radioactivity was also recovered as free cholesterol, especially during the embryonic phase. Triglycerides were also formed from acetoacetate in a high proportion in liver from neonatal animals. 4. Chick kidney showed the maximal ability to incorporate both precursors into amino acids. The peak obtained around hatching time would be related to the availability of the substrates. 5. Ketone body oxidation to CO2 was also maximal in kidney. In this tissue, a drastic decrease was observed during the final embryonic period, followed by a strong increase at day 1 after hatching and a new decrease at 4 days. PMID- 8359016 TI - PCR amplification of partial mRNA sequences encoding the alpha- and beta-globin chains of the bivalve mollusc Anadara trapezia: correction of the C-terminal amino acid sequence of the alpha-chain. AB - 1. PCR was carried out on cDNA which had been synthesized from poly(A)+ RNA extracted from A. trapezia red blood cells. 2. A 348 bp product encoding the C terminal region of the alpha-globin chain and another product encoding a portion of the beta-globin chain were isolated. 3. The C-terminal alpha-chain sequence, encoded by the cDNA, differs from the previously published sequence and these changes improve the alignment of this chain with the other globin chains of this organism. PMID- 8359017 TI - Fatty acid and lipid composition in vitro and in vivo of rat epidermis. AB - 1. Fatty acid and lipid compositions of cultured rat keratinocytes were compared with those of intact epidermis prepared from newborn and adult rats. 2. The uniqueness of the lipid profile of cultured cell manifested itself in the accumulation of a novel lipid which co-migrated with monoalkyldiacylglyceride on thin-layer chromatography. 3. Concentration of the branched-chain fatty acid was specifically high in the cholesterol ester fraction of the intact cell, and was decreased by cultivation under submerged conditions. PMID- 8359018 TI - Protein synthesis in ovine muscle and skin: sequential measurements with three different amino acids based on the large-dose procedure. AB - 1. Protein synthesis has been determined in biopsies from ovine skin and muscle by sequential use of three [13C] amino acids, valine leucine and phenylalanine, as large-dose injections. 2. Leucine and phenylalanine increased plasma insulin concentrations within 40 min of injection. 3. All three amino acids decreased the plasma concentrations of other amino acids. 4. Intracellular free amino acids in muscle decreased while those in skin increased. 5. The fractional rates of protein synthesis were similar, regardless of which amino acid was used, although the rates for muscle were significantly less than for skin (2.1 vs 11.0%/day, P < 0.001). PMID- 8359019 TI - Temporal synthesis of cuticle proteins during larval development in Glossina morsitans. AB - 1. Larval development in Glossina species occurs in utero with the mature third instar larva being deposited after a developmental period of 7 days. 2. In this study, the patterns of cuticular protein synthesis during larval development were analysed by two-dimensional gel electrophoresis. 3. From the results, four types of cuticle proteins were identified: those specific to larval, pupal and adult cuticles, and others common to all the stages. 4. Few cuticular proteins were synthesized between the first and second larval instars. By the third larval instar (two days before larviposition), a large number of proteins (Mr < or = 30 kDa) were induced. These proteins persisted up to the brown pupal stage and showed a rapid decline thereafter. Most of the proteins with molecular weights Mr < or = 30 kDa were undetectable at apolysis (5 days after larviposition). 5. By day 15 of the pupal stage, the number of cuticle proteins was very small. The protein profile during the pupal stages remained relatively constant. This was probably due to the fact that the pupal cuticle does not provide any protection since it is itself enclosed at all times within the protective puparium. PMID- 8359020 TI - Transthyretin expression evolved more recently in liver than in brain. AB - 1. Transthyretin was found to be synthesized and secreted by choroid plexus from rats, echidnas, and lizards, but not toads. 2. Transthyretin was observed in blood from placental mammals, birds, and marsupials, but not reptiles and monotremes. 3. The obtained data suggest that transthyretin synthesis by the liver evolved independently in the lineage leading to the placental mammals and marsupials and in that leading to the birds. 4. It is proposed that transthyretin gene expression in mammalian liver appeared about 200 million years later than its first occurrence in the choroid plexus of the stem reptiles. PMID- 8359021 TI - Occurrence of a furin-like prohormone processing enzyme in Aplysia neuroendocrine bag cells. AB - 1. Strong evidence is accumulating that the endoproteases which process prohormones at dibasic residue cleavage sites are members of a subtilisin-related class of proteases. 2. Using the polymerase chain reaction (PCR), we have isolated and characterized an Aplysia californica neuroendocrine bag cell cDNA product (270 base pairs) that encodes a sequence which is highly homologous to the subtilisin-related class of processing proteases that includes yeast Kex2, human/mouse/Drosophila furin, human PC2, and mouse PC1/PC3 and PC2. 3. The characterized cDNA PCR product showed the highest degree of residue identity with the furin-related group of proteins (human/mouse furin 71%; Drosophila furin 63%). 4. These results establish that Aplysia contain a subtilisin-like gene and suggest that the expression of this gene may play a role in processing Aplysia precursor proteins in the bag cells and likely also in the exocrine atrial gland. 5. Furthermore, the Aplysia nucleotide sequence results, together with available sequence information from human, mouse, and Drosophila furins, provide reasonable evidence that the furin-like enzymes may represent a separate subclass of the subtilisin-like processing enzymes. PMID- 8359022 TI - Characterization of a partial cDNA clone encoding porcine skeletal muscle titin: comparison with rabbit and mouse skeletal muscle titin sequences. AB - 1. A cDNA fragment encoding 571 amino acid residues of porcine skeletal muscle titin was isolated from total RNA using RNA-PCR. 2. The porcine titin clone hybridized to a large RNA species (> 23 kb) in rabbit cardiac muscle, rabbit skeletal muscle and porcine skeletal muscle. 3. The porcine skeletal muscle titin clone encoded two types of 100-residue motifs and its amino acid sequence was 96% and 93% identical to the corresponding sequence of rabbit and mouse skeletal muscle titin, respectively. These results suggest that the titin sequence is highly conserved among mammalian species. PMID- 8359023 TI - Immunological and charge properties of GFAP in lower vertebrates. AB - 1. An antiserum specific for bovine GFAP was employed in a comparative study of this protein in several species of bony fish and in an anuran species. 2. The immunological properties of this protein are conserved in a remarkable way in all the species examined. 3. Analysis of trout and bovine GFAP by two-dimensional gel electrophoresis indicated that the charge properties of this protein have remained quite constant from fish to mammals. PMID- 8359024 TI - Glycogen phosphorylase activity in the liver of the frog Rana esculenta. AB - 1. Phosphorylase activity has been assayed in liver extracts of the frog, Rana esculenta, during the winter period. In native conditions, most of the phosphorylase is present as AMP-independent activity and shows properties similar to those of the a form of the liver enzyme from other vertebrates. 2. It is suggested that regulation of phosphorylase activity is through interconversion between a and b forms operated by endogenous phosphorylase kinase and phosphatase. 3. Kinetic studies show hyperbolic saturation curves for glycogen with apparent Km of 2.91 mM and 9.67 mM for a and b forms, respectively. 4. A hyperbolic saturation curve is also observed for glucose 1-P in the case of phosphorylase a, with an apparent Km of 3.95 mM, whereas a sigmoidal kinetic is shown by the b form for the same substrate; from Hill plots an S0.5 of 24.2 mM was derived. 5. Hyperbolic responses were observed in the case of AMP, and Ka of 70 microM and 0.31 mM were calculated for phosphorylase a and b, respectively. PMID- 8359025 TI - Thermal gradients in the eyes of lid-sutured chicks. AB - Thermal gradients were measured from the cornea to the posterior pole in the eyes of 11 chicks, six of which had the lids of one eye sutured three weeks previously. A comparison was made between eyes that were chronically closed by lid-suture (while still sutured shut) and two types of control eyes: (a) treated controls, which were the non-sutured, contralateral eyes of the lid-sutured chicks and (b) untreated controls, which were the eyes of a different group of chicks in which neither eye had been sutured. The results indicated that transient closing of the eyes of normal, untreated chicks (untreated controls) elevated the ocular temperature by about 1.5 degrees C at the cornea; the extent of thermal elevation diminished as the thermoprobe was advanced towards the posterior pole. In contrast, when the transiently closed eyes in untreated control chicks were compared with the chronically closed eyes of the lid-sutured chicks, the lid-sutured eyes were cooler by 2 degrees - 2.5 degrees. When the sutured lids were opened, however, the eyes were isothermal with the untreated control eyes. Moreover, the eyes of lid-sutured chicks were isothermal with their contralateral, non-sutured, control eyes (treated control), whether in the opened or closed state. A comparison of the untreated control eyes and the treated control eyes revealed no differences (except at the cornea) when the eyes were opened; but when the eyes were closed, the treated control eyes were 2 degrees - 3 degrees cooler than the untreated control eyes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359026 TI - The effect of caffeine on the accommodative response/accommodative stimulus function and on the response AC/A ratio. AB - Using a phoro-accommodometer, accommodation and convergence responses were measured for 17 experimental subjects before and after they ingested 200 mg caffeine. For 16 control subjects accommodation and convergence responses were determined at two test sessions separated by 45 min. For the experimental group, the accommodative response/accommodative stimulus (Ar/As) slope increased 0.05 D/D after ingestion of caffeine, and the response AC/A ratio decreased 3.05 delta/D. The y-intercept of the convergence response/accommodative response increased by 3.7 delta in the experimental group. These changes were statistically significant. For the control group, the differences in Ar/As slope, response AC/A ratio, and convergence response/accommodative response y-intercept between first and second test sessions were not statistically significant. PMID- 8359027 TI - Soft drugs 15: mydriatic activity and transcorneal penetration of phenylsuccinic soft analogs of methscopolamine as short acting mydriatics. AB - Soft drug analogs of methscopolamine (4 a-c) were tested for mydriatic activity in rabbits' eyes. After unilateral administration of equieffective doses, the AUC24hrs and the mydriatic recovery times were found to be significantly lower with the soft drugs compared to methscopolamine. At equieffective doses, the AUC24hrs for soft drugs ranged from 22.4% to 60% of that of methscopolamine. Significant dilation of the untreated eye was observed with methscopolamine but not with the soft drugs after unilateral administration. Soft drug 4a exhibited only 10.4% of the AUC6hrs (untreated eye) of that of methscopolamine. Shorter durations of mydriatic action combined with potentially reduced systemic side effects make these compounds candidates for further study. In vitro rabbit transcorneal penetration of soft analog 4a was found to be significantly higher than methscopolamine. PMID- 8359028 TI - Evolution of morphologic changes after intravitreous injection of gentamicin. AB - Gentamicin shows retinal toxicity in rabbits, monkeys, and humans, but its mechanism of toxicity is not understood. Pig eyes, which are anatomically similar to human eyes, were examined with ophthalmoscopy, fluorescein angiography, and light and electron microscopy at time points ranging from 3 to 72 hours after intravitreous injection of 3 mg of gentamicin or vehicle to observe the sequence of toxicity-related changes that occur in the retina. The first ophthalmoscopic changes were retinal hemorrhages at 3 hours, followed by retinal whitening and thickening and vascular nonperfusion detected by fluorescein angiography 48 hours after injection. Vacuolization in the nerve fiber layer and perivascular swelling were seen at 6 hours, and subsequently, extended deeper into the retina. Vascular endothelial cells, photoreceptors, and the retinal pigment epithelium appeared to be spared from the toxic effects of gentamicin. At 48 and 72 hours after injection, numerous large and small retinal vessels showed congestion and leukocyte margination. These changes could not be prevented by increasing the pH of gentamicin to 7.2. These data suggest that gentamicin toxicity is not simply a pH-related phenomenon, that the primary targets of gentamicin toxicity are neurons and glia of the inner retina, and that retinal infarction occurs secondarily, possibly due to leukocytic plugging. PMID- 8359029 TI - Separation and characteristics of glycoproteins in tears which inhibit coating and precipitation of protein. AB - Using a modified turbidimetric assay to determine the protein concentration in human tears by precipitation with trichloroacetic acid (TCA) we found lower protein concentrations if compared with other methods for protein determination. This implies that a factor in human tears is able to inhibit the precipitation of protein by TCA. Earlier a coating inhibitory factor in human tears was described which is able to prevent coating of a polyacrylate surface by proteins using a ELISA methodology. Because of the similarity in its behaviour towards protein we investigated whether the same factor could be responsible for both inhibitory effects. A pool of human tears was separated into various fractions using HPLC whereafter inhibitory activity in the turbidimetric and the coating assay could be found in the same fractions. Characterization of the inhibitory factor was performed by minigel-electrophoresis (SDS-PAGE), after which blotting and staining with a lectin (Jacalin) revealed two subunits of a glycoprotein with a molecular weight of 30 and 70 kD. The inhibitory factor also could be isolated if human tears were incubated for 30 min at 100 degrees C whereafter precipitated protein was removed by centrifugation. Inhibitory activity could be detected in the supernatant and an identical glycoprotein profile could be produced after staining with lectin (Jacalin). The results of this study suggest that a soluble glycoprotein serves as a coating and precipitation inhibitor in tears and may play an important role in the protein to protein interaction on the surface of the eye. PMID- 8359030 TI - In vitro inhibition of collagen formation by 2,4-pyridine dicarboxylate and minoxidil in rabbit corneal fibroblasts. AB - Two anti-fibrotic agents were evaluated in vitro for potential application in trabeculectomy. The rate of collagen formation by cultured rabbit corneal fibroblasts was determined by [3H]proline uptake and hydroxylation assay. Incubation of fibroblasts, for 96 hours, with 16 mM 2,4-pyridine dicarboxylic acid (2,4-PDCA), a competitive inhibitor of prolyl 4-hydroxylase, decreased [3H]OH-proline formation from control by 28.2 +/- 3.9%; (average +/- S.E.M), whereas 10 mM minoxidil, an antihypertensive pyrimidine oxide and a lysyl hydroxylase inhibitor, induced a decrease of 17.3 +/- 4.5%. Incubating fibroblasts with a mixture of the two inhibitors, 16 mM 2,4-PDCA and 10 mM minoxidil, resulted in a further decrease in [3H]proline incorporation of 40.7 +/ 5.1%. After 96 hours of incubation with the inhibitors, rabbit corneal fibroblast growth was decreased from control by 17.2 +/- 4.2% and 10.5 +/- 4.5% for 16 mM 2,4-PDCA and 10 mM minoxidil, respectively. These effects were dose dependent. The results suggest that both 2,4-PDCA and minoxidil have an inhibitory effect on collagen formation and may be useful in delaying surgical wound healing. PMID- 8359031 TI - Fluorescein angiography as a means of assessing retinal vascular pathology in oxygen-exposed newborn rats. AB - Recently a new technique was reported in which examination of the retina of oxygen reared newborn rats was made using indirect fluorescence microscopy (Invest. Ophthal. Vis. Sci. 31:810). We have now improved this technique and systematically employed it as a means of studying oxygen-induced retinopathy in the newborn rat as an animal model for retinopathy of prematurity (ROP). Immediately after birth, litters of pigmented rats were exposed to an elevated oxygen atmosphere that varied in a cyclic fashion between 40% and 80% every 12 hours for 14 days. Rats raised simultaneously in room air served as controls. At the end of the treatment period, rats were deeply anesthetized, their pupils dilated, and 100 microliters of 3% sodium fluorescein was administered via tail venipuncture. After angiography, rats were awakened and returned to their mothers in room air for future assessment. Angiography was performed again at 4, 7, 38 or 56 days after oxygen treatment. Our results suggest that retinal pathology in the rat model parallels that of the human infant with ROP with respect to loss of patent retinal blood vessels in oxygen and subsequent abnormal vasoproliferation upon return to room air. Angiograms performed on room air-raised control rats at 14 days of age demonstrated our ability to resolve the smallest retinal capillaries. Angiograms conducted at the same age in oxygen-exposed rats revealed extensive areas of retinal non-perfusion and substantial arterio-venous shunting between adjacent primary vessels. If rats were maintained in room air for 4 or 7 days following oxygen exposure, a variety of pathologic signs became obvious including: 1) tortuosity of primary vessels mimicking human "plus disease", 2) frequent abnormal budding of tertiary vessels and capillaries, 3) retinal fluorescein leaks indicative of hemorrhages and 4) abnormal capillary tufts not evident at the time of removal from oxygen. By 38 and 56 days post-exposure, all four of these phenomena were still observed. Many of these pathologic phenomena could not have been observed with conventional methods currently used for retinal vascular assessment in small animals. PMID- 8359032 TI - Keratoconus corneas: increased gelatinolytic activity appears after modification of inhibitors. AB - We examined the metalloproteinase activity from normal and keratoconus corneal extracts. No differences were detected in the total amount of the metalloproteinase or its physical form of activation. However, there was a significant elevation in enzymatic activity in the keratoconus extracts after chemical modification of inhibitory elements. This suggests either a difference in the enzymatic capabilities of keratoconus corneas or, as suggested previously, a decrease in the amount of TIMP (tissue inhibitor of metalloproteinase) present in the tissue. PMID- 8359033 TI - Radiology of maxillofacial trauma. AB - There has been a rising incidence of maxillofacial injuries during the past decade as a result of an increasing number of assaults and motor vehicle accidents. The maxillofacial region is one of the most complex areas of the human body, and the radiographic imaging of this region becomes even more difficult in traumatized patients because of their clinical condition and their inability to cooperate. Imaging modalities used in the evaluation of the traumatized maxillofacial region include conventional (plain) films, tomography, panoramic radiography, computed tomography, three-dimensional computed tomography, DentaScan, and magnetic resonance imaging. Each modality is discussed with regard to technique, advantages, and disadvantages. Plain films and computed tomography, the modalities that are used most in evaluating maxillofacial structures, are discussed in more detail. The normal anatomy and radiologic features are presented for both of these modalities. Radiographic evaluation of maxillofacial injury begins with a knowledge of the direct and indirect radiographic signs of injury seen on most imaging modalities. Computed tomography also has allowed a method of classifying facial fractures that is based on the involvement of the facial buttresses or struts. Three horizontal, two coronal, and five sagittal oriented struts are described. Limited fractures are differentiated from transfacial fractures by the lack of involvement of the pterygoid plates in the limited fractures. Limited fractures also can be subclassified as solitary (fracture of a single strut) or complex (fractures of multiple struts). A portion of the orbit is involved in almost every form of facial fracture; therefore, evaluation of facial injuries should always include the orbital structures. Although both can occur simultaneously, orbital injuries can be divided into soft tissue and bony vault injuries. Similar to midface fractures, orbital fractures also can be classified as solitary (fracture involves a single wall) or complex (fracture involves more than one wall or a part of a midface fracture). Computed tomography is of great value in evaluating both forms of injury. Magnetic resonance imaging is becoming increasingly important in the evaluation of orbital soft tissue injuries. Classification of midface injuries includes the solitary strut fractures and the complex strut fractures. Solitary strut fractures include fractures of the nasal arch, zygomatic arch, and isolated sinus wall fractures. Complex strut fractures include the nasal complex fractures, zygomatic (tripod) and zygomaticomaxillary fractures, transfacial fractures (LeFort fractures), and facial smash fractures. Each fracture type and its radiographic appearance are discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8359034 TI - Special issue: A festschrift for Martin W. Donner, M.D. PMID- 8359035 TI - Dysphagia diagnostics and Donner: experiences in the decade of change. AB - Martin Donner's influence in the area of dysphagia diagnostics has spanned several decades and has provided an impetus for the evolution of advanced dysphagia diagnostics. This article presents an historical perspective of the development of ultrasound imaging and the variety of other imaging procedures to evaluate swallowing. The future of image processing for dysphagia is firmly set. PMID- 8359036 TI - The probability of correctly predicting subglottic penetration from clinical observations. AB - It is difficult to predict from clinical signs and symptoms which patients suffer from subglottic penetration of foods. Most investigators attempting to predict aspiration have used small numbers of patients and relatively unsophisticated statistical techniques. In this study, we utilized 249 patients to examine the predictive value of several clinical factors thought to be suggestive of subglottic penetration with discriminant analysis. Using this approach we were able to correctly predict about 2/3 of both those who aspirate and those who do not aspirate. This is better than others have reported but still inadequate for clinical purposes. PMID- 8359037 TI - Speech-language pathology and dysphagia: a brief historical perspective. AB - In the past decade, speech-language pathologists have taken a leading role in the management of services for patients with oropharyngeal dysphagia. This article presents the historical perspective of this role, the rationale for assuming the responsibility, and suggests directions for continued involvement. PMID- 8359038 TI - The search for the central swallowing pathway: the quest for clarity. AB - As the work of Dr. Martin Donner has brought a clarity to understanding swallowing, so has the work of various neuroscientists, including that of a Nobel Laureate, in providing us with a better comprehension of this complex motor pattern. Understanding the neural control of swallowing has been a process that has occurred during this century in which several investigators, primarily from Europe, Japan, Canada, and the United States, have brought their perspectives in applying particular techniques to decipher how the central and peripheral nervous system control swallowing. Swallowing represents a complex muscular response of the oral, pharyngeal, and esophageal regions which are integrated to provide an effective functional pattern that prepares and transports food while simultaneously protecting the airway. This adaptation of the upper gastrointestinal tract in mammals has been extensively studied peripherally by two methods: recording from the peripheral nerves and muscles, and stimulating peripheral nerves and their receptive fields that can induce the pharyngeal and esophageal phases of swallowing. The study of the peripheral nervous system has provided insight into the sensory receptive fields that evoke or facilitate swallowing, and has established the first serious evidence of the all-or-none sequential contraction pattern of the oropharyngeal and esophageal muscles. It has been these electromyographic studies of the muscles that has established much of the criteria for evaluating the central swallowing pathway. Five techniques have been applied to the central nervous system to study swallowing and include lesioning or destroying discrete regions to determine how swallowing is impaired or modified, electrically stimulating the central neural tissue to determine the type of effects on swallowing, recording from the central neural tissue with macro- and microelectrodes to ascertain when neurons respond in timing to the peripheral muscle activity during swallowing, applying pharmacological agents through micropipettes which could mimic or inhibit potential transmitters, and using immunochemical techniques to tag specific chemicals that could be transmitters used by the neurons in the central swallowing pathway. These various techniques have provided insight into how the central swallowing pathway is organized but the details of the central control are still in the process of being defined and will require as much effort this next century as has been previously developed over the past 90 years. PMID- 8359039 TI - The role of the cerebral cortex in swallowing. AB - This paper reviews clinical, neuroanatomical, and neurophysiological studies that have implicated the cerebral cortex in the initiation and/or regulation of swallowing as well as related functions such as mastication. Cortical dysfunction has been reported to result in a variety of swallowing impairments. Furthermore, swallowing can be evoked and/or modulated by stimulation applied to restricted regions of the cortex. Neuroanatomical investigations and single neuron recording studies also provide some insights into the cortical structures, pathways, and mechanisms that may mediate deglutition. PMID- 8359040 TI - A protocol for the videofluorographic swallowing study. AB - This paper presents a detailed protocol for performing the videofluorographic swallowing study (VFSS), and describes how it evolved from its antecedents. The objectives of the VFSS are both diagnostic and therapeutic. Preparing for the VFSS is described, including the equipment, food preparation, and a brief discussion of the clinical evaluation. The detailed description of the VFSS procedure covers the position of the patient, the foods presented, the views obtained, modifications of feeding and swallowing that are commonly employed, the standardized set of observations, and reporting the results. Criteria for deviating from the protocol or aborting the study are presented. The VFSS does not necessarily end when a patient aspirates. Indeed, the complete evaluation of aspiration, and the effects of maneuvers designed to reduce it, is a major purpose of the VFSS. Modifications of feeding and swallowing are tested empirically during the study. The modifications include therapeutic and compensatory techniques that may improve the safety and efficiency of swallowing. A rationale for deciding which modifications to test in a given patient is discussed. The protocol has been used successfully in more than 350 patients. It has improved the efficiency and quality of our videofluorographic examinations. PMID- 8359041 TI - The evaluation of pediatric feeding abnormalities. AB - An appreciation of normal age-related feeding behavior is a prerequisite for the study of pediatric feeding disorders. When faced with a child with dysphagia, the diagnostic evaluation including history, physical and developmental exam, and feeding observation, followed by appropriate diagnostic tests forms the basis for understanding the underlying pathophysiology and the anticipated developmental progression. It makes possible the formulation and implementation of an optimal treatment strategy, which can be monitored for results and modified when needed. Four case examples are provided. PMID- 8359042 TI - The functions of saliva. AB - Oral health is determined to a considerable extent by our ability to produce saliva. Not only must adequate amounts be produced, but a large number of specific proteins also must be secreted for the mouth to function properly. This brief review is directed at describing (1) how saliva is secreted, (2) the consequences of decreased salivary function, (3) the components necessary for oral homeostasis, and (4) the common causes of salivary hypofunction. PMID- 8359043 TI - Oropharyngeal swallowing after stroke in the left basal ganglion/internal capsule. AB - One of the foci of Martin Donner's work was the neural control of swallowing. This present investigation continues that work by examining oropharyngeal swallowing in 8 patients identified with a single, small, left-basal ganglion/internal capsule infarction and 8 age-matched normal subjects. Stroke patients were assessed with a bedside clinical and radiographic swallowing assessment, and normal subjects received only the radiographic study. Results revealed disagreement between the bedside and radiographic assessments in one of the 8 stroke patients. Stroke and normal subjects differed significantly on some swallow measures on various bolus viscosities, but behaved the same as normal subjects on a number of measures. Differences in swallowing in the stroke subjects were not enough to prevent them from eating orally. The significant differences seen in the basal ganglia/internal capsule stroke subjects may result from damage to the sensorimotor pathways between the cortex and brainstem. These differences emphasize the importance of cortical input to the brainstem swallowing center in maintaining the systematic modulations characteristic of normal swallowing physiology. PMID- 8359044 TI - Clinically probable brainstem stroke presenting primarily as dysphagia and nonvisualized by MRI. AB - Ten patients with clinically probable brainstem stroke presenting primarily as acute dysphagia but without visible brainstem abnormality by MRI are described. The patients were evaluated with neurologic examinations, cinepharyngoesophagography, and brain MRI studies. Each patient solely or predominately experienced sudden pharyngeal dysphagia, and additional symptoms or signs other than dysphonia or dysarthria were scarce. Small vessel disease or cardiac embolism were the apparent causes of what appear to have been very discrete brainstem strokes in these patients. Acute pharyngeal dysphagia can be the sole or primary manifestation of brainstem stroke. A negative MRI study should not preclude consideration of this diagnosis, if brainstem stroke is otherwise clinically probable. PMID- 8359045 TI - Pharyngeal constrictor paresis: an indicator of neurologic disease? AB - Pharyngeal constrictor paresis (PHCP) is sometimes found in videoradiography of the swallowing act in patients complaining of dysphagia. Ten patients with PHCP and 10 dysphagic, age- and sex-matched controls with normal videoradiography were neurologically evaluated and examined with magnetic resonance imaging (MRI) of the brain and brainstem in order to learn the pathogenetic process behind PHCP. The study revealed 8 PHCP patients and 1 dysphagic control with abnormal clinical neurological findings such as myopathy, cerebrovascular disease, or extrapyramidal disease. The neurological examination revealed considerable information of prognostic and therapeutic value in PHCP patients. The MRI was abnormal in 7 PHCP patients and 4 dysphagic controls. However, the findings in MRI were nonspecific but the examination was found to be valuable in selected cases. It is concluded that PHCP is an indicator of neurological disease and accordingly, such patients should be examined by a neurologist to establish the cause of the disease. PMID- 8359046 TI - Cricopharyngeal function and dysfunction. AB - The cricopharyngeus is a narrow band of muscle strategically placed between the pharynx and esophagus. Its normal function is vital to the efficient transfer of foodstuffs to the esophagus. Cine- and videoradiography are the major methods of studying the pharyngo-esophageal segment. More recently, refinements in manometric methods have complemented radiology, and have enabled us to achieve a better understanding of cricopharyngeal function in health and disease. Such an understanding of the physical forces necessary for normal bolus transfer, and the recognition of abnormal patterns of pharyngeal and cricopharyngeal motility, will hopefully lead us to a more rational approach to therapy in patients with pharyngeal dysphagia. PMID- 8359047 TI - The role of cricopharyngeus muscle in pharyngoesophageal disorders. AB - The cricopharyngeus muscle is generally thought to be responsible for the high pressure zone of the pharyngoesophageal (upper esophageal) sphincter. In this review we critically examined the evidence for the role of the cricopharyngeus muscle in the manometric pharyngoesophageal sphincter. The available studies show disparities between the anatomic location of the cricopharyngeus muscle and the manometric high pressure zone of the pharyngoesophageal sphincter. The cricopharyngeus muscle seems to correspond to the distal 1/3 of the sphincteric high pressure zone and the peak high pressure zone appears to be located proximal to the cricopharyngeus muscle. The discrepancy between the upper high pressure zone and the anatomic cricopharyngeus is important in understanding the role of the cricopharyngeus muscle in the pathophysiology and treatment of clinical disorders of the pharyngoesophageal sphincter. PMID- 8359048 TI - Volume accommodation during swallowing. AB - Bolus volume is an important modifier of the biomechanical events of the oropharyngeal swallow. The biomechanical events comprising a swallow can be divided into events associated with the reconfiguration of the pharynx into a swallow pathway and events associated with bolus transport from the oropharynx into the esophagus. Volume modification is achieved differently for the events of reconfiguration and propulsion. In the case of reconfiguration, a longer time is allocated to the process, as exemplified by sustained laryngeal elevation and hyoid excursion during larger volume swallows. On the other hand, in the case of bolus expulsion, volume accommodation is accomplished within the same period of time by utilizing increased vigor of expulsion. The result of deglutitive volume accommodation is a remarkably different fluoroscopic appearance of a small vs. a large volume swallow. The larger volume swallow seemingly takes longer and results in much more vigorous bolus expulsion than a small volume. However, this is more related to the bolus than the swallow. PMID- 8359049 TI - Dysphagia and expiratory air flow. AB - Expiratory air flow preserves the freedom of the upper airway from foodway contamination in patients with dysphagia. Valving the tracheostomy cannula, "quad coughing," the Heimlich maneuver, the "supraglottic swallow," and coupling to a ventilator each has a place among the measures used for treating aspiration. PMID- 8359050 TI - Modern solid state computerized manometry of the pharyngoesophageal segment. AB - There has been renewed interest in the use of manometry of the pharyngoesophageal segment in the investigation of pharyngeal dysphagia. Advances in technology have alleviated previous difficulties presented by factors such as the rapid response rate of the striated muscle and asymmetry of the upper esophageal sphincter. Close attention to technique can overcome difficulties with movement artifacts encountered during deglutition. Manometry is being used to study normal swallow function and the effects of physiologic changes. There are also increasing numbers of reports in the literature of manometric studies in patients with oropharyngeal dysphagia. This technique provides information on pressure changes and augments that information obtained from a barium swallow. PMID- 8359053 TI - [Reimbursement for elective procedures based on the health care restructuring legislation]. PMID- 8359052 TI - Malignancy-induced secondary achalasia. AB - Secondary achalasia refers to the development of clinical, radiographic, and manometric findings of achalasia as a result of (i.e., secondary to) another underlying disorder. A variety of malignancies have been associated with secondary achalasia. Adenocarcinoma of the esophagogastric junction accounts for the majority of cases of malignancy-induced achalasia, however, noncontiguous tumors may also cause this disorder. Although rare, malignancy-induced achalasia will occasionally be encountered by gastroenterologists and gastrointestinal radiologists who see patients with dysphagia and/or achalasia. Since treatment is aimed at the underlying neoplasm, it is important to recognize this disorder. Three clinical features suggest the possibility of malignancy as a cause of achalasia: 1) short duration of dysphagia (< 1 year); 2) significant weight loss (> 15 pounds); and 3) age > 55 years. The presence of any of these should at least raise a suspicion of malignancy. Diagnosis may not be evident on routine esophagrams and endoscopy, and requires clinical suspicion for further evaluation with thoraco-abdominal CT scanning and endoscopic ultrasonography. PMID- 8359051 TI - Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management. AB - Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125 fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials. PMID- 8359054 TI - [Classification and grading of soft tissue tumors]. PMID- 8359055 TI - [Preoperative chemotherapy in treatment of soft tissue sarcoma]. PMID- 8359056 TI - [Surgical therapy and prognosis of soft tissue sarcoma]. PMID- 8359057 TI - [Soft tissue sarcoma: isolated hyperthermic extremity perfusion. Technique and indications]. PMID- 8359058 TI - [Soft tissue tumors: indications and results of hyperthermia]. PMID- 8359059 TI - [Value of sonography in diagnosis of uncertain lesions of the abdominal wall and inguinal region]. AB - In a prospective trial we investigated the value of ultrasound in 134 patients with clinical doubtful findings of the abdominal wall and inguinal region. Ultrasound diagnosis was made by predefined criteria. In 105 patients a definite diagnosis was made by means of operative findings, CT, NMR, or puncture. In 40 patients a hernia was found. The sensitivity of ultrasound was 85%, the specifity 93.8%, the positive predictive value as 89.5% and the negative predictive value was 91%. Separating the findings to localisation of the hernia results in highest sensitivity for epigastric hernia (100%) and lowest for crural hernia (72.7%). The specifity for all hernias was more than 96%. Liquid tumors (hematom, serom, abscess) could be differentiated from solid tumors (lymphom, metastatic nodule, lipom). The most frequent course of wrong diagnosis was mixing the different liquid or solid tumors among themselves because of similar sonomorphologic properties. The sensitivity for hematom, serom, abscess, lymphom and metastatic nodule was 87.5%, 100%, 66.6%, 77% and 85.7% respectively. The corresponding specifity was 97.8%, 97.8%, 100%, 96.7% and 98%. Ultrasound was found to be of value for the diagnosis of clinical indeterminal findings of the abdominal wall and inguinal region. PMID- 8359060 TI - [Value of image analysis DNA cytometry in cancer of Vater's ampulla]. AB - In 27 patients who underwent partial duodenopancreatectomy due to cancer of the ampulla of Vater, in addition to the TNM classification and usual morphologic criteria, the paraffin-embedded material underwent deparaffinization, was rehydrated, and was mechanically and enzymatically processed into a single-cell solution. For evaluating the DNA histogram this was analyzed with the help of automatic single cell cytophotometric study. At the time of DNA analysis the histomorphological data and the survival time of the patients were not known. In the univariate analysis the 5-year survival rate of patients with diploid or hypotriploid tumors (n = 12) was 69% of patients with diclonal (diploid-triploid n = 7, triploid-tetraploid n = 1) tumors was 62.5% and no patient with a triploid or hypertriploid tumor (n = 7) survived 5 years. No association could be found between the known prognostic criteria and the DNA content. The multivariate analysis shows that beside the lymph node status, the DNA content of tumor cells had a strong and independent influence on the prognosis in cancer of the ampulla of Vater. PMID- 8359061 TI - [Lack of effectiveness of alternative non-surgical treatment procedures of Dupuytren contracture]. AB - In the early stage of the disease a group of patients was treated with radiotherapy, later another group with injections of superoxid-dismutase. The results of follow-up examinations 7 years after radiotherapy and 3 years after treatment with superoxid-dismutase respectively do not differ clearly from spontaneous course of Dupuytren's contracture grade one. At present we cannot recommend an alternative treatment for early stage Dupuytren's contracture. PMID- 8359063 TI - [Monstrous Buschke-Loewenstein tumor (condylomata acuminata gigantea) with transition to invasive squamous epithelial cancer]. AB - The case of a 34-year-old female is reported, who has suffered from recurring condylomata acuminata of the anogenital region since she was 16. In the further course of the disease multiple Buschke-Loewenstein tumors developed, and finally an invasively growing, highly differentiated, keratinizing squamous cell carcinoma. The course of the disease was complicated by severe septicemia. In the framework of multimodal therapy, laser resection was the preferred method of surgical intervention. A systemic or local interferon treatment has only a prophylactic character in this stage of the disease. PMID- 8359062 TI - [Dorsolateral approach to the left subphrenic area, to the bursa omentalis and to the cauda pancreatis]. AB - We are reporting on a dorsolateral access left to the bursa omentalis and to the left subphrenium carried out in order to relieve infectious processes in this region. The access has proved a success above all in the later postoperative period, e.g. when the protecting conglutinations towards ventral isolate the process from the abdominal cavity. At the lying patient this access allows the drainage of the exsudation over the deepest point. The results of 23 surgical interventions are being demonstrated with references to possible complications caused by the intervention. PMID- 8359064 TI - [Recurrent lung embolisms in aneurysm of the popliteal vein]. AB - Report about a rare case of pulmonary embolism caused by a clinically unsuspected aneurysm of the popliteal vein. The aneurysm was suitable for local venous reconstruction. The diagnosis and the treatment are discussed. PMID- 8359065 TI - [Limited surgery of breast cancer]. PMID- 8359066 TI - U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. AB - Our objective was to obtain national data of the estimated prevalence, sociodemographic relationships, and health impact of persons with functional gastrointestinal disorders. We surveyed a stratified probability random sample of U.S. householders selected from a data base of a national market firm (National Family Opinion, Inc.). Questions were asked about bowel symptoms, sociodemographic associations, work absenteeism, and physician visits. The sampling frame was constructed to be demographically similar to the U.S. householder population based on geographic region, age of householder, population density, household income, and household size. Of 8250 mailings, 5430 were returned suitable for analysis (66% response). The survey assessed the prevalence of 20 functional gastrointestinal syndromes based on fulfillment of multinational diagnostic (Rome) criteria. Additional variables studied included: demographic status, work absenteeism, health care use, employment status, family income, geographic area of residence, population density, and number of persons in household. For this sample, 69% reported having at least one of 20 functional gastrointestinal syndromes in the previous three months. The symptoms were attributed to four major anatomic regions: esophageal (42%), gastroduodenal (26%), bowel (44%), and anorectal (26%), with considerable overlap. Females reported greater frequencies of globus, functional dysphagia, irritable bowel syndrome, functional constipation, functional abdominal pain, functional biliary pain and dyschezia; males reported greater frequencies of aerophagia and functional bloating. Symptom reporting, except for incontinence, declines with age, and low income is associated with greater symptom reporting. The rate of work/school absenteeism and physician visits is increased for those having a functional gastrointestinal disorder. Furthermore, the greatest rates are associated with those having gross fecal incontinence and certain more painful functional gastrointestinal disorders such as chronic abdominal pain, biliary pain, functional dyspepsia and IBS. Preliminary information on the prevalence, socio-demographic features and health impact is provided for persons who fulfill diagnostic criteria for functional gastrointestinal disorders. PMID- 8359067 TI - Irritable bowel-type symptoms in HMO examinees. Prevalence, demographics, and clinical correlates. AB - A study of irritable bowel-type symptoms in 1264 health examinees using a self administered questionnaire and psychological tests revealed they are common throughout adulthood. Of affected subjects 68% were female, and those with the more severe type (> or = 3 Manning criteria) were predominantly female (80%). Fewer Asians than other racial/ethnic groups had these symptoms. Nongastrointestinal symptoms, physician visits, incontinence, laxative use, a stress effect on bowel pattern and abdominal pain, abdominal surgery, hysterectomy, childhood abuse, use of mind-altering drugs, depression, and anxiety were correlated with irritable bowel-type symptoms. Regression analysis found some of the clinical correlates were independent markers for irritable bowel-type symptoms and that sexual abuse was related to nongastrointestinal symptoms and abdominal surgery independent of irritable bowel-type symptoms. More severe irritable bowel-type symptoms were especially associated with nongastrointestinal symptoms, stress effects, sexual abuse, use of sedatives and oral narcotics, and a past alcohol problem. There are important demographic and clinical correlates with irritable bowel-type symptoms. PMID- 8359068 TI - Terminal ileal mucosal mast cells in irritable bowel syndrome. AB - Terminal ileal biopsies were prospectively obtained and stained specifically for mast cells in 20 patients with irritable bowel syndrome (IBS) and 15 controls. The number of terminal ileal mast cells per high powered field (MC/HPF) (mean +/- SEM) was 23.3 +/- 3.1 for IBS and 6.8 +/- 1.1 for controls (P = 0.0001). The diarrhea IBS subgroup had the greatest number of MC/HPF. No correlation was found between terminal ileal mucosal mast cell counts (MMCC) and the number of Manning criteria present or the functional bowel disease score (r = 0.06 and r = -0.31, respectively). We conclude that terminal ileal MMCC are significantly elevated in a majority of patients with IBS. The mast cell may be responsible for the altered visceral perception found in the gastrointestinal tract in patients with IBS. The poor correlation of the MMCC to the clinical features of IBS may be the result of the dynamic state of the mast cell. PMID- 8359069 TI - Oral contraceptive use and cigarette smoking in Crohn's disease. AB - Previous studies have consistently found strong positive associations between smoking and Crohn's disease. The association between oral contraceptive use and Crohn's disease remains, however, controversial. In order to analyze whether smoking and oral contraceptive use are independent risk factors, a case-control study was performed. In 90 women with Crohn's disease and 90 community controls information was assessed about their smoking habits and their use of oral contraceptives. Smoking and oral contraceptive use were associated with one another. After adjusting for oral contraceptive use, the relative risk for smokers compared with nonsmokers was 3.0 (1.3-6.8). After controlling for smoking, the relative risk estimates for oral contraceptive use were for no use, 1-3 years, and > 3 years of use 1.0, 2.5 (1.0-6.6), and 4.3 (1.3-14.4), respectively. When oral contraceptive use was stratified by smoking habits, the data show that oral contraceptives only increased the risk for Crohn's disease in nonsmokers. From the lack of increase in risk for combined exposure, it is concluded that both factors might act through a common mechanism. PMID- 8359070 TI - Indium scanning in assessment of acute Crohn's disease. A prospective study of sensitivity and correlation with severity of mucosal damage. AB - The aim of this study was to determine whether the sensitivity of indium-111 (111In) scanning in the assessment of the activity and extent of Crohn's disease correlates with the severity of intestinal lesions as measured by the newly validated Crohn's disease endoscopic index of severity (CDEIS). Nineteen patients with active (CDAI > 200) colonic (N = 11) or ileocolonic (N = 8) Crohn's disease were assessed by colonoscopy and indium scanning. The intestine was divided into five segments in both studies (rectum, sigmoid and left colon, transverse colon, right colon, and ileum). Seventy of the 86 intestinal segments seen at colonoscopy presented macroscopic lesions of Crohn's disease. On third-hour scintigrams 111In uptake was observed in 52 segments, 51 of which were found to be abnormal at colonoscopy. Predictive positive and negative values of scanning with respect to disease extent assessment were equal to 98% and 44%, respectively. Complete agreement between endoscopic and scintigraphic findings was observed in only six of the 19 patients (32%). Segmental endoscopic indexes of severity (SEIS) were significantly (P < 0.001) lower in false negative (7.9 +/ 4.2) (mean +/- SD) than in true positive (18.0 +/- 9.7) segments as defined by scintigraphy. SEIS values above which 111In uptake was constantly observed did not differ in the different disease locations. When compared macroscopically abnormal intestinal segments according to their 111In uptake grade, the corresponding mean SEIS values increased significantly as the grade increased. Scintigraphic activity, as assessed by the fall in splenic activity, was equal to 23 +/- 11% (N = 19).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359071 TI - Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition (TPN). AB - We examined the small intestinal histology disaccharidase activities as well as the incorporation of [3H]thymidine into DNA of biopsies maintained in organ culture from seven children (ages 9 months to 5 years) receiving total parenteral nutrition (TPN). Three children suffered from inflammatory bowel disease and received TPN for one month (short term). Four required long-term TPN (> 9 months) for short-bowel syndrome. DNA was extracted from the samples following serial precipitation with perchloric acid. Results were compared to those from 22 age matched children investigated for abdominal pain or chronic diarrhea. Short-term TPN resulted in slightly lower lactase, sucrase, and palatinase activities that were not statistically different from controls. Long-term TPN resulted in focal mild villus atrophy and a decrease in disaccharidase activity in two patients. Biopsies from long-term TPN patients incorporated less thymidine compared to those of controls (P < 0.001) when data was expressed per total biopsy (3.6 +/- 1.1 vs. 8.4 +/- 1.1 fmol) or per milligram of tissue (1.0 +/- 0.12 vs 2.7 +/- 0.7 fmol). The above data are in general agreement with the hypoplastic effect of TPN in animals. However, in children, much longer periods of TPN are required to realize the changes. PMID- 8359072 TI - Multiple vitamin status in Crohn's disease. Correlation with disease activity. AB - We measured serum, blood, or red cell concentrations of various vitamins in 24 patients with Crohn's disease who had been free from any nutritional treatment, and compared them with those in 24 healthy controls. Twelve of the patients were affected in the small bowel only, two in the large bowel only, and the remaining 10 in both the small and large bowel. The fat-soluble vitamins A and E were significantly decreased in patients with Crohn's disease compared to controls. Among the water-soluble vitamins, vitamins B1, B2 and B6 and folic acid were more depleted in patients with Crohn's disease than in the controls, whereas vitamins B12 and C, nicotinic acid, and biotin were not different between the two groups, and pantothenic acid was increased in patients with Crohn's disease. In addition, vitamin B2 and nicotinic acid showed a negative correlation with the Crohn's disease activity index. These findings suggest that there is a variety of vitamin deficiencies in Crohn's disease prior to treatment and also that concentrations of some vitamins, such as vitamin B2 and nicotinic acid, may reflect the severity of the disease. PMID- 8359073 TI - Nonsteroidal antiinflammatory drugs and lower gastrointestinal bleeding. AB - To define the association of the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA), and lower gastrointestinal bleeding (GIB) a retrospective, case-controlled study was undertaken of 188 patients admitted to three community hospitals in three cities with a diagnosis of lower GIB. Information was obtained about NSAID usage among these patients, and the data were compared with an age- and sex-matched control group of 185 patients admitted with a nongastrointestinal diagnosis, derived from a daily admission list. At the time of admission, in the New Jersey group, NSAID consumption was present in 26 of 90 (29%) patients with lower GIB compared with 16 of 90 (18%) of controls (P < 0.05, odds ratio 1.88, 95% CI 1.2-3.1) whereas, in the South Carolina group 34 of 98 (35%) were taking NSAID compared with 18 of 95 (19%) of controls (P < 0.01, odds ratio 2.27, 95% CI 1.2-4.4). These data indicate that there is a significantly increased rate of NSAID ingestion in patients admitted with lower GIB, implying that NSAID may unmask bleeding from a variety of lower gastrointestinal lesions. PMID- 8359074 TI - Effect of oral cyclosporin on renal function in Crohn's disease. AB - Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0, 6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m2; at six weeks: 100.9 ml/min/1.73 m2; mean ERPF at baseline: 497.3 ml/min/1.73 m2; at six weeks: 398.5 ml/min/1.73 m2). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m2), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m2). Serum creatinine rose significantly (median pretreatment 72 mumol/liter; median at four weeks 86 mumol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction. PMID- 8359075 TI - PMN-elastase in assessment of patients with inflammatory bowel disease. AB - PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5 +/- 33.2 ng/ml vs 60.1 +/- 24.6 ng/ml (mean +/- SD), P = 0.0017; ulcerative colitis: 98.2 +/- 54.9 ng/ml vs 59.2 +/- 16.8 ng/ml, P = 0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6 +/- 15.3 ng/g vs 13.6 +/- 12.5 ng/g, P = 0.0021) and active ulcerative colitis (46.5 +/- 60.5 ng/g vs 20.2 +/- 25.0 ng/g, P = 0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma: r = 0.72, P < 0.001; feces: r = 0.57, P = 0.002). In patients with Crohn's disease only plasma levels of PMN-elastase (r = 0.423, P < 0.001) but not fecal elastase concentrations (r = 0.0083, P = 0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r = 0.431, P < 0.01) and in ulcerative colitis (r = 0.515, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359077 TI - Intestinal permeability to [51Cr]EDTA in infectious diarrhea. AB - Orally administered [51Cr]EDTA was used to measure intestinal permeability in subjects with infectious diarrhea and in those without gastrointestinal complaints. [51Cr]EDTA was given to 87 subjects: 63 controls (32 normal controls, and 31 disease controls), and 24 patients with infectious diarrhea. Approximately 100 microCi of [51Cr]EDTA was given orally after an overnight fast. Urine was collected for the following 24 hr. Intestinal permeability to [51Cr]EDTA in both normal volunteers and in patients with a variety of diseases not associated with intestinal injury was low and results were in a relatively narrow range. Mean 24 hr urinary excretion of [51Cr]EDTA, calculated as a percent of the administered dose, in controls was 1.6% (0.2-3.5%). Patients with infectious diarrhea associated with invasive pathogens and/or intestinal inflammation had increased excretion of [51Cr]EDTA (mean 6.1%, P < 0.0001), with elevated excretions in 75%. These results demonstrate that intestinal infections must be considered as possible causes for increased intestinal permeability as assessed by the [51Cr]EDTA test. PMID- 8359076 TI - Effect of alpha-methylnorepinephrine, an alpha 2-adrenergic agonist, on jejunal absorption in neurally intact conscious dog. AB - Although alpha 2-adrenergic agonists stimulate absorption in the mammalian small and large intestine in vitro, the possibility of central neural effects have confounded interpretation of in vivo studies. Our aim was to assess the effects of intravenous administration of alpha-methylnorepinephrine (MNE), an alpha 2 adrenergic agonist that does not cross the blood-brain barrier, on net jejunal absorption of water and electrolytes in the neurally intact, conscious dog. Absorption from a 30-cm proximal jejunal segment was studied using a triple-lumen perfusion technique in seven dogs. A warmed, isosmolar, balanced electrolyte solution containing [14C]polyethylene glycol was infused at 5 ml/min. Net jejunal fluxes of water and electrolytes were determined before, during, and after a 1.5 hr infusion of MNE (900 nmol/kg/hr). MNE increased net jejunal water absorption (from 12.9 +/- 1.8 to 22.5 +/- 1.5 microliters/cm/min, P < 0.05). Peripheral alpha 2-adrenergic receptors mediate a net proabsorptive response in the neurally intact canine jejunum in vivo independent of direct central neural effects. PMID- 8359078 TI - Insulin, IGF-1, and IGF-2 receptors in rat small intestine following massive small bowel resection. Analysis by binding, flow cytometry, and immunohistochemistry. AB - This study was undertaken to correlate changes in insulin, IGF-1, and IGF-2 receptors in enterocytes both during the phase of active hyperplasia (protocol 1) and the phase of initiation of hyperplasia (protocol 2) induced by 60% proximal jejunoileal resection in rats. Hormone binding to purified receptor preparations, indirect immunofluorescence analysis by flow cytometry, and immunohistochemistry were used to identify receptor changes. Insulin and IGF-2 receptor binding were increased in the intestine two days after surgery and prior to increased cell mass. The number of cells expressing insulin and IGF-1 receptors increased two- and three-fold between 12 and 36 hr after resection, whereas IGF-2 receptors were maintained throughout the 48-hr period. A significant increase in immunoreactive IGF-2 receptors in both the villus and crypt regions of the jejunum and ileum was observed 12 hr after resection, and this increase was maintained in the crypt region of the jejunum through 48 hr. Therefore, insulin and IGF-2 receptors appear to be important in the initiation of cellular hyperplasia following resection. PMID- 8359079 TI - One-day therapy for treatment of Helicobacter pylori infection. AB - The present study evaluated the effect of a one-day high-dose combined therapy on Helicobacter pylori infection. Thirty-two consecutive patients (suffering from either peptic ulcer or nonulcer dyspepsia) with Helicobacter pylori infection received omeprazole (40 mg) + bismuth subcitrate (240 mg x 4) + amoxicillin suspension (2000 mg x 4) + metronidazole (500 mg x 4), for only one day. Endoscopy, histology, culture, and susceptibility studies were done at entry and 30 and 90 days after the treatment day. Successful eradication was obtained in 23/32 (72%) patients and gastritis had resolved in 95% of these. Side effects were induced by the treatment in 6/32 (19%) patients, but these were all self limiting, short-lasting, and did not require any specific treatment. Development of bacterial resistance to metronidazole occurred in 6/9 (67%) non-eradicated patients. These data suggest that one-day treatment with high doses of amoxicillin, metronidazole, bismuth, and omeprazole represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection. PMID- 8359080 TI - Bismuth subsalicylate suppression of Helicobacter pylori in nonulcer dyspepsia: a double-blind placebo-controlled trial. AB - Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement. PMID- 8359081 TI - Asymptomatic H. pylori infection impairs pH inhibition of gastrin and acid secretion during second hour of peptone meal stimulation. AB - H. pylori infection is associated with acid-peptic disease, although its role in the pathogenesis is unclear. The purpose of this study was to determine if chronic infection in asymptomatic subjects impairs the inhibition of meal stimulated gastrin and acid secretion that is observed normally at low intragastric pH. Presence of infection was determined by both C-14 urea breath test and serology. Acid secretion was measured under basal conditions and in response to peptone meal stimulation and pentagastrin. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and during peptone meal stimulation. Intragastric titration with 1% peptone during the first hour, and 8% peptone during the second hour, was performed at both pH 7.0 and 2.5 on different days to compare the inhibition of gastrin and acid secretion. Compared to noninfected subjects, asymptomatic individuals infected with H. pylori had significantly increased: (1) basal gastrin values (P < 0.005); (2) 8% peptone-stimulated gastrin responses at both pH 7.0 and 2.5 (P < 0.05); and (3) 8% peptone-stimulated acid output at pH 2.5 (P = 0.01). During the second hour of peptone-stimulation, subjects infected with H. pylori had significantly decreased inhibition of gastrin (52% vs 95%) (P = 0.002) and acid (30% vs 81%) (P = 0.01) secretion from pH 7.0 to 2.5. Thus, chronic infection with H. pylori results in impaired inhibition of gastrin and acid secretion at low intragastric pH during the second hour of peptone meal stimulation. These defects may be unrelated to the pathogenesis of acid-peptic disease, since they occur in asymptomatic subjects infected with H. pylori. PMID- 8359082 TI - Helicobacter pylori infection, ABO blood group, and effect of misoprostol on gastroduodenal mucosa in NSAID-treated patients with rheumatoid arthritis. AB - Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers. PMID- 8359083 TI - Production of chemoattractant by Helicobacter pylori. AB - Helicobacter pylori is present in the antral region of the stomach in a majority of patients with gastritis type B. The specific mechanism whereby the organism participates in the development of disease remains uncertain. Since the organism is not invasive, we postulate that H. pylori produces a chemoattractant that recruits inflammatory cells to the antral region of the stomach. H. pylori was grown under microaerophilic conditions at 37 degrees C for 72 hr in Brucella broth containing 1% fetal bovine serum. Culture supernates were harvested after removal of organisms by centrifugation and filtration. The putative chemoattractant in culture supernates as well as that which might be present endogenously in the growth medium (negative control) was assayed against human neutrophils (PMN) in modified Boyden blind-well chambers using 3.0-microns membranes. We found that H. pylori supernates are chemotactic and showed up to 130% activity when compared to the positive chemoattractant control (zymosan activated serum, a source of C5a). Minimal activity was observed with virgin growth medium. The chemoattractant activity is proportional to the number of colony forming units (CFU) of H. pylori. Preliminary characterization of the activity shows that the chemoattractant is stable in a boiling water bath for 15 min, activity is lost within 1 hr in acid or alkali, and the chemotactic factor has an approximate molecular weight of 8500 daltons. The factor has no amino sugar and is negative for the lipid A portion of lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359084 TI - ESWL and oral dissolution therapy. What factors influence results? AB - With the aim of identifying the criteria that have a decisive influence on the success of treatment of gallstones with ESWL and oral dissolution therapy, we investigated, in 117 patients, the stone-free rate as a function of sex, age, weight quotient, number of stones, total stone volume, and gallbladder function. The following inclusion criteria were applied: (1) the Munich criteria, (2) a follow-up period of at least 12 months, or (3) freedom from stones irrespective of the duration of the period of follow-up. Although, owing to the small number of cases involved, no significantly differing results were seen in the parameters investigated, clear tendencies were indeed observed. While age, sex, and weight quotient appear to have no influence on the stone-free rate, the number of stones, total stone volume, and gallbladder function do appear to have an effect on the results of treatment. Patients with solitary stones not more than 20 mm in diameter, and patients with a small total stone volume and good gallbladder function would appear to have the best chance of becoming stone-free within a short period of time, irrespective of age, sex, or girth. PMID- 8359085 TI - Effect of extracorporeal shock wave lithotripsy and ursodeoxycholic acid on gallbladder motility. AB - Extracorporeal shock wave lithotripsy and dissolution agents are useful nonsurgical therapies for gallstones. Their effect on gallbladder emptying is unclear. We evaluated emptying by ultrasonography before and after lithotripsy in 50 patients on ursodeoxycholic acid or placebo and in nine controls. At baseline, patients had normal (68.8 +/- 3.2%) or delayed emptying (14.5 +/- 3.3%). In a subset of 24 patients, lithotripsy increased fasting volume (26.6 +/- 3.0 to 43.8 +/- 5.0 ml, P < 0.005), postprandial volume (11.3 +/- 3.1 ml to 22.9 +/- 3.0 ml, P < 0.05), and decreased ejection fraction (70.0 +/- 4.1% to 42.7 +/- 6.0%, P < 0.0005). There was an inverse linear correlation between power and ejection fraction, r = -0.43, P < 0.005. Ursodeoxycholic acid increased fasting (23.3 +/- 2.2 ml to 36.7 +/- 4.6 ml, P < 0.005) and postprandial volume (11.1 +/- 1.8 to 17.6 +/- 2.5, P < 0.005). Treatment with ursodeoxycholic acid resulted in a greater decrease in fragment size compared to placebo after lithotripsy in patients with fragment size greater than 6 mm. In conclusion, both lithotripsy and ursodeoxycholic acid have an effect on gallbladder emptying. PMID- 8359086 TI - Cholescintigraphic study of effect of somatostatin analog, octreotide, on bile secretion and gallbladder emptying in normal subjects. AB - The objective of the study was to investigate the effects of a single intravenous injection of the somatostatin analog octreotide on hepatic bile secretion and gallbladder emptying with a quantitative scintigraphic technique. Twelve healthy volunteers received, in a double-blind randomized fashion, either octreotide, 100 micrograms intravenously, or placebo. Ten minutes later, [99mTc]PBIDA was administered intravenously (50 microCi/kg) (time = 0) followed, 60 min later, by the ingestion of a standardized fatty meal. In the liver area, the relative decrease per minute of tracer activity from the time of maximal activity to 60 min was significantly lower in the octreotide group (P = 0.02). In the gallbladder area, after the fatty meal, the ratio of tracer activity at 60 and 90 min (A90/A60) was significantly (P = 0.01) higher in the octreotide group. Our study demonstrates that octreotide slows down liver release of the radiopharmaceutical, probably reflecting decreased bile secretion, and inhibits postprandial gallbladder contraction. PMID- 8359087 TI - Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. AB - The use of oral and intravenous cyclosporin represents a significant advance in the therapy of refractory inflammatory bowel diseases (IBD). However, oral administration of cyclosporin is fraught with improper delivery of cyclosporin to the colon for its topical action. Because of unpredictable metabolism by cytochrome P-450 IIIA, the targeted blood level for systemic effect is not reached at low doses. Furthermore, the doses that have been used for therapy of IBD have been shown to induce several adverse side effects. Thus, an alternate method of delivering cyclosporin to the colon is desirable. In this study, the effect of intracolonically administered cyclosporin was tested for its efficacy to heal mucosal erosions in dextran sulfate sodium (DSS)-induced colitis in mice. Both acute and chronic colitis was induced by feeding female Swiss-Webster mice with 5% DSS (30,000-40,000 mol wt) for five or seven days, respectively. Therapy was advocated prophylactically, prophylaxis plus therapy and therapeutically during the acute and chronic phase of the disease and therapeutically during the chronic phase of the disease. Intracolonic cyclosporin given prophylactically showed adverse effects by increasing the damage to the colonic mucosa. However, intracolonic cyclosporin given therapeutically in 2.5, 5, and 10 mg/kg after the induction of colitis resulted in dramatic responses in terms of reducing the disease activity and histologic scores, corroborated by complete histological resolution compared to oral cyclosporin given at identical doses. Intracolonic cyclosporin (5 mg/kg) was also very effective in reducing the chronic inflammation. The results of this study highlight the application of this animal model for therapeutic research. Furthermore, cyclosporin administered as an enema provides a new stratagem for the therapy of IBD because of its rapid onset of action at very low doses without the risk inherent in oral or systemic administration. PMID- 8359089 TI - Intractable neurological Wilson's disease treated with orthotopic liver transplantation. PMID- 8359090 TI - Recurrent fulminant hepatic failure in an HB carrier after intensive chemotherapy. PMID- 8359091 TI - Cholestatic hepatitis following flutamide. PMID- 8359088 TI - Intestinal epithelial function: the case for immunophysiological regulation. Implications for disease (2). AB - Substantial amounts of data have been reported showing a role for immunomodulation of epithelial function (particularly ion secretion and permeability) using animal models of anaphylactic reactions. In part one of this review we outlined the main immune cell types and mediators/cytokines that are currently known to influence epithelial physiology either directly, or indirectly via an intermediate cell type. Here we will expand on the significance of these studies and show how antigenic activation of the mucosal immune system can evoke changes in epithelial function that may be beneficial to the host by mediating loss/inactivation of the antigen. However, a continued and inappropriate immune stimulation can lead to pathophysiological reactions and disease. Thus, we will present data on immune regulation of epithelial function with direct applicability to understanding the mechanism underlying human intestinal inflammatory and secretory disease. Finally, we highlight key strategic points in the cascade of immune events that can control epithelial function and thus may be of relevance in the formulation of new therapeutic approaches to intestinal inflammation. PMID- 8359092 TI - Obesity, diabetes, and hyperlipidemia in a central Australian aboriginal community with a long history of acculturation. AB - OBJECTIVE: To determine the age- and sex-specific prevalence of diabetes and to examine associations between related anthropometric and metabolic abnormalities in an Aboriginal community in central Australia with a long history of acculturation. RESEARCH DESIGN AND METHODS: We used a cross-sectional survey of 353 adults > 15 yr of age (87% response rate) and measured the following parameters: weight, height, circumferences of waist and hips; glucose, insulin, cholesterol, triglyceride, and high-density lipoprotein cholesterol in fasting plasma; and plasma glucose and insulin 2 h after 75 g oral glucose. RESULTS: The prevalence of diabetes was 29.6% in survey participants > 35 yr of age and 5.3% in those < 35 yr of age. Impaired glucose tolerance also occurred with higher frequency in those > 35 yr of age (14.8 vs. 4.7%). Of those > 35 yr of age, 75% of the women and 51% of the men were overweight or obese, with a body mass index > or = 25 kg/m2. A large insulin response to oral glucose was evident, with the upper tertile of the 2-h insulin response six times higher than the lower tertile (113 +/- 43 vs. 19 +/- 8 mU/L). Hyperinsulinemia showed a strong, positive association with impaired glucose tolerance, body mass index, waist-to-hip ratio, cholesterol, and triglyceride levels and a negative association with high-density lipoprotein cholesterol levels. Cholesterol levels were on average 0.5 mM higher in men than in women. Deteriorations in carbohydrate and lipid metabolism occurred before 40 yr of age: diabetes, body mass index, waist-to-hip ratio, and fasting triglycerides and cholesterol concentrations peaked and high-density lipoprotein cholesterol concentrations reached their nadir at the end of the fourth decade. CONCLUSIONS: These data suggest that any intervention programs developed to prevent or reduce diabetes prevalence in this population should be targeted at adolescents and young adults. PMID- 8359093 TI - Evidence for a role for insulin and growth hormone in overnight regulation of 3 hydroxybutyrate in normal and diabetic adolescents. AB - OBJECTIVE: To determine the relative effects of growth hormone and insulin on ketogenesis during puberty. RESEARCH DESIGN AND METHODS: We studied overnight changes in plasma ketones--3-hydroxybutyrate and acetoacetate--in 35 normal and 26 IDDM adolescents at different stages of puberty. The diabetic adolescents either were on their normal insulin regimen or were studied during an overnight euglycemic clamp with or without suppression of endogenous growth hormone release. RESULTS: Total ketone body and 3-hydroxybutyrate concentrations in the normal adolescents rose significantly from 2000 (29 +/- 5 microM), reaching a peak at 0200 (103 +/- 16 microM, P < 0.001 vs. 2000). After a brief fall, a further rise occurred before breakfast. Fasting 3-hydroxybutyrate concentrations showed a negative correlation with fasting insulin levels (r = -0.46, P = 0.005) and decreased with advancing puberty, while insulin concentrations increased. In the diabetic patients on their usual insulin regimen, free insulin levels waned overnight, and an exaggerated rise in ketones was observed before breakfast. During the euglycemic clamp studies, ketone levels were higher than normal throughout the night. Mean overnight growth hormone and free insulin levels also were higher than in the normal control subjects. The addition of the anticholinergic drug pirenzepine reduced growth hormone secretion and obliterated the early-night peak of 3-hydroxybutyrate. CONCLUSIONS: We conclude that the early-night peak of ketone concentrations is related to growth hormone release, whereas the fasting levels are largely determined by insulin concentration. Inadequate insulin delivery in the presence of the high growth hormone concentrations characteristic of diabetic adolescents could lead to rapid decompensation and ketoacidosis. PMID- 8359094 TI - Vascular dysfunction detected by a simplified venous occlusion test in NIDDM patients. AB - OBJECTIVE: To elucidate the relationship between angiopathies and vascular function evaluated by a simplified venous occlusion test in patients with NIDDM. RESEARCH DESIGN AND METHODS: The serum concentration of FDP was measured before and 5 min after venous occlusion in 23 NIDDM patients, 11 patients with cerebrovascular accident, and 10 age-matched healthy control subjects. RESULTS: The increment of serum FDP level after venous occlusion was significantly less in patients with NIDDM (60.6 +/- 33.5 to 81.5 +/- 49.6 ng/ml) and in those with cerebrovascular accident (101.4 +/- 51.5 to 116.2 +/- 47.2 ng/ml) than in control subjects (79.9 +/- 41.0 to 148.8 +/- 65.4 ng/ml). The increment of serum FDP after venous occlusion in NIDDM patients with macroangiopathy was significantly lower than that in those without macroangiopathy. CONCLUSION: The responsiveness of fibrinolytic activity to venous occlusion was significantly less in NIDDM patients with macroangiopathy, as in patients with cerebrovascular accident, compared with that in healthy control subjects. PMID- 8359096 TI - Effective treatment of insulin-induced edema using ephedrine. AB - OBJECTIVE: To control insulin-induced edema in a patient with poorly controlled IDDM. RESEARCH DESIGN AND METHODS: A 31-yr-old woman with a 14-yr history of poorly controlled IDDM first developed peripheral edema 3 yr after diagnosis of IDDM; the edema worsened whenever insulin dosage was increased. In August 1991, severe edema developed after treatment of ketoacidosis, with body weight increasing from 46 to 61 kg. No evidence of cardiac dysfunction or autonomic neuropathy existed, and serum albumin was consistently normal. RESULTS: Treatment with 15 mg of ephedrine every 8 h produced a prompt diuresis, with body weight falling by 4 kg in 48 h and by 12 kg within 1 wk. CONCLUSIONS: Ephedrine may be an effective treatment for insulin-induced edema and may be preferable to the use of diuretics in such patients. PMID- 8359095 TI - Prevalence of cardiovascular and renal complications in older adults with normal or impaired glucose tolerance or NIDDM. A population-based study. AB - OBJECTIVE: To determine the prevalence of CVD and renal disease by glucose tolerance status in a population-based study. RESEARCH DESIGN AND METHODS: The study consisted of 991 men and 1243 women, aged 50-89 yr, living in the upper middle class community of Rancho Bernardo, CA. All participants received a standard OGTT between 1984 and 1987. RESULTS: A total of 159 men and 158 women had NIDDM, whereas 237 men and 348 women had IGT. Age-adjusted prevalence of complications generally was highest in those who were previously diagnosed with NIDDM. A significant correlation was observed between increases in the prevalence of complications and increases in glucose intolerance for microproteinuria, macroproteinuria, and myocardial infarction (borderline), as well as for stroke and claudication in men and myocardial infarction and stroke in women. In men with IGT or NIDDM, the age-adjusted prevalence of proteinuria and CVD was highest when other complications were present whereas in women such a prevalence was highest when other complications were absent. In men with diabetes, microproteinuria was associated with duration of disease. CONCLUSIONS: Prevalent CVD and renal disease were increased in adults with NIDDM and elevated in adults with IGT compared to those with normal glucose tolerance. The prevalence of complications in NIDDM subjects in this population-based study was substantially lower than that reported for clinic-based diabetic populations. PMID- 8359097 TI - Association between fish intake and coronary heart disease mortality. Differences in normoglycemic and glucose intolerant elderly subjects. AB - OBJECTIVE: To compare the association of habitual fish intake with 17-yr mortality of coronary heart disease between normoglycemic and glucose intolerant elderly subjects. RESEARCH DESIGN AND METHODS: In 1971, 272 men and women, 64-87 yr of age, were examined in a general practice in the town of Rotterdam, The Netherlands. Glucose intolerance (impaired glucose tolerance or diabetes mellitus) was observed in 83 subjects, and 189 subjects were found to be normoglycemic and free of clinically diagnosed diabetes mellitus. Information on usual dietary intake was obtained using the cross-check dietary history method. RESULTS: Fish consumption was found in 58.7% of the normoglycemic population and in 62.4% of the glucose intolerant population. Among normoglycemic subjects, the age- and sex-adjusted 17-yr mortality for coronary heart disease was 10.9/1000 person-yr for those who ate fish and 25.1/1000 person-yr for those who did not. For the glucose intolerant population, the rates were 20.6/1000 and 31.2/1000 person-yr, respectively. Adjusted for age, sex, body mass index, smoking, alcohol use, intake of energy, polyunsaturated fat, and carbohydrates, the risk ratio for normoglycemic population was 0.34 (95% confidence interval: 0.16-0.72). For glucose intolerant subjects, an adjusted risk ratio of 0.80 (95% confidence interval: 0.31-2.05) was observed. CONCLUSIONS: These results suggest that in a glucose intolerant population the possible protective effect of fish intake on coronary heart disease may be smaller than in normoglycemic subjects. PMID- 8359099 TI - Carbohydrate and dietary management of individuals with insulin-requiring diabetes. PMID- 8359098 TI - Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. AB - OBJECTIVE: To compare the metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. RESEARCH DESIGN AND METHODS: After a 2-wk run-in period on dietary treatment alone, 12 Chinese normotensive patients with uncomplicated NIDDM were randomized to receive either metformin, or glibenclamide for 4 wk before being crossed-over to the alternative treatment for an additional 4 wk. Metabolic and hemodynamic index, including cardiac output estimation by impedance cardiography, were measured at baseline and at the end of each treatment period. RESULTS: Body mass index was reduced more with metformin than with glibenclamide, although glycemic control was similar with both drugs. Plasma total cholesterol concentration fell more with metformin (mean difference 0.65 mM, 95% confidence interval -0.96 to -0.32) than glibenclamide (mean difference -0.20 mM, 95% confidence interval -0.54-0.12) (P < 0.05). Compared with baseline values, erect diastolic blood pressure was reduced more by metformin (12.9% [95% confidence interval -21.5 to -4.4%]) than glibenclamide ( 6.8% [95% confidence interval -14.9 to 1.2%]) (P < 0.001). The relative changes in the systemic vascular resistance index also differed between the two treatments (glibenclamide, 6.2 [-4.3 to 16.6%]; metformin, -1.2 [95% confidence interval -8.8-6.4%]) (P < 0.05)]. CONCLUSIONS: In normotensive NIDDM patients, treatment with metformin was associated with greater reductions in body weight, plasma total cholesterol concentration, and erect diastolic blood pressure, whereas the systemic vascular resistance index increased after treatment with glibenclamide. These findings merit long-term investigation. PMID- 8359100 TI - Finding the right fit for meal planning. PMID- 8359101 TI - Should the bee suck honey or lard? That is the question. PMID- 8359102 TI - Extensor plantar response in diabetic neuropathy. PMID- 8359103 TI - Hunger--a common symptom of hypoglycemia. PMID- 8359104 TI - What is a significant change in the level of HbA1c? PMID- 8359105 TI - Acute insulin response to glucose and glucagon in subjects at risk of developing type I diabetes. AB - OBJECTIVE: To determine if knowledge of characteristics of insulin response to various secretagogues during the preclinical phase of type I diabetes may facilitate the diagnosis of subjects at risk. RESEARCH DESIGN AND METHODS: A test consisting of sequential intravenous challenge with glucose (0.3 g/kg) and glucagon (1 mg, 10 min after the end of glucose injection) was performed on 171 ICA- relatives of type I diabetic patients, 18 ICA+ relatives of type I diabetic patients, and 5 transiently hyperglycemic subjects. Acute response to glucose was expressed as the sum of plasma insulin at 2 and 5 min and response to glucagon as the increase in plasma insulin after 10 min. RESULTS: Responses below the lower 95% confidence interval in the ICA- population (40 and 43 microU/ml for glucose and glucagon, respectively) were considered abnormal. The two values were correlated (r = 0.62). Abnormalities coexisted in 2.3% of the ICA- group, 11% of the ICA+ group, and 100% of the transiently hyperglycemic group. All the relatives who subsequently developed diabetes or hyperglycemic subjects who required insulin exhibited combined abnormalities. Some ICA- and ICA+ relatives were tested repeatedly over a follow-up period of 1.5-4 yr. Although the intraindividual coefficient of variation for the two responses was high (28 and 30%), values tended to run parallel in both ICA+ and ICA- relatives. In 2 patients monitored for 2 and 4 yr before diabetes developed, both responses declined at the same rate. In terms of prediction of diabetes, sensitivity of combined abnormalities was high (100%). But compared with the intravenous glucose tolerance test, improvement of specificity by the double challenge was not statistically significant. CONCLUSIONS: Both insulin responses to glucose and glucagon are related. They depend on the secretory capacity of beta-cells and simultaneously become abnormal in the prediabetic phase. PMID- 8359106 TI - Stability over time of modern diagnostic criteria for type II diabetes. AB - OBJECTIVE: To examine the long-term stability of the World Health Organization criteria for diabetes in the 8-yr follow-up of the San Antonio Heart Study. A problem with older criteria for diagnosing diabetes was that many individuals classified as having borderline or chemical diabetes reverted to nondiabetic status on follow-up. Few studies have addressed this issue among diabetic patients who meet the more stringent, modern National Diabetes Data Group or World Health Organization criteria. RESEARCH DESIGN AND METHODS: We studied 98 Mexican-American and 44 non-Hispanic white type II diabetic patients 8 yr after they were diagnosed according to World Health Organization criteria in a population-based epidemiological survey. Patients were classified as follows: whether they were on pharmacological treatment for diabetes at baseline, or, if not, whether they had a prior diagnosis of diabetes at the time of their baseline survey visit or were newly diagnosed. RESULTS: Of the 142 patients who met the study criteria for type II diabetes at baseline and whose status at follow-up was known, 20 (14.1%; 95% confidence interval 9.0-20.5%) no longer met criteria at follow-up 8 yr later. All but 2 of those who reverted to nondiabetic status were from the newly diagnosed group. Two of 20 had lost more than 5.0 kg over the 8 yr and an additional 5 had lost 2.5-5.0 kg. The 20 patients who reverted to nondiabetic status lacked many of the associated anthropometric, physiological, and metabolic findings of diabetes such as obesity, unfavorable body fat distribution, and dyslipidemia. Moreover, only one had proteinuria, and none had any grade of diabetic retinopathy at baseline. CONCLUSIONS: Epidemiological surveys that rely on a single oral glucose tolerance test to determine the prevalence of type II diabetes may overestimate prevalence by as much as 16% (95% confidence interval 10.5-23.6%) (142/122 = 1.16). The actual overestimate could well be less because some patients who truly have diabetes at baseline may be in remission at follow-up as a result of significant weight loss. Despite these difficulties, the modern National Diabetes Data Group and World Health Organization criteria are more stable than earlier criteria. PMID- 8359107 TI - Seven years of remission in a type I diabetic patient. AB - OBJECTIVE: To analyze factors contributing to a long-term remission in a patient with type I diabetes. RESEARCH DESIGN AND METHODS: The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and beta-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects. RESULTS: Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr. CONCLUSIONS: In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr. PMID- 8359108 TI - A prospective population-based study of microalbuminuria as a predictor of mortality in NIDDM. AB - OBJECTIVE: To assess prospectively the relationship between microalbuminuria and mortality in a geographically defined population of NIDDM patients and to determine the relative importance of microalbuminuria as a risk factor for mortality. RESEARCH DESIGN AND METHODS: A survey of known diabetes undertaken in 1982 identified a cohort of 249 NIDDM patients. Follow-up information was available for 246 patients who contributed 1498 person-yr exposure and were followed up for a mean period of 6.1 yr. The median age of the cohort at entry was 68 yr (range 28-89 yr), and the median duration of diabetes was 7 yr (range 1 41 yr). At baseline, a clinical examination was performed and a random daytime urine specimen was obtained for measurement of urinary albumin concentration. RESULTS: UAC results were available for 236 patients: 45 (19%) patients had a UAC > 15- < 40 mg/L; 36 (15%) had a UAC 40-200 mg/L; 10 (4%) had a UAC > 200 mg/L; and 145 (61%) had a normal UAC < or = 15 mg/L. During the follow-up period, 93 patients died. All-causes mortality, expressed as standardized mortality ratio (SMR = 149) and coronary heart disease mortality (CHD SMR = 166) were significantly increased. This excess mortality was significant in women (all causes SMR = 194, CHD SMR = 234) but not in men (all-causes SMR = 118, CHD SMR = 128). On univariate analysis, systolic blood pressure was the only significant association with albumin concentration (P = 0.0002). An age-stratified log-rank test was conducted to determine the effect of potential explanatory variables on survival. Survival distributions were significantly different for known duration of diabetes (P = 0.045), intermittent claudication (P = 0.012), severity of retinopathy, lens opacity (P < 0.001) and UAC (P = 0.013) and diastolic blood pressure approached significance (P = 0.051). After adjusting for the effects of these potentially confounding variables identified by the log-rank analysis, significant predictors of early mortality on multivariate survival analysis were age, UAC of 40-200 mg/L (relative risk = 2.2, 95% confidence interval 1.3-3.7), more severe retinopathy (relative risk = 3.4, 95% confidence interval 1.9-6.0), and lens opacity (relative risk = 2.4, 95% confidence interval 1.6-3.8). CONCLUSIONS: The findings from this population-based cohort confirm the predictive power of microalbuminuria as a risk factor for mortality in NIDDM. In contrast to prospective studies of conventional cardiovascular risk factors in NIDDM, consistent evidence indicates that microalbuminuria is an independent predictor of excess mortality regardless of the collection procedure used. PMID- 8359109 TI - Restenosis after coronary angioplasty. AB - Coronary angioplasty is used to treat coronary disease in many patients. Indications for angioplasty have expanded since it was first performed, mainly as a result of improvement in equipment and techniques. One problem with coronary angioplasty is the phenomenon of renarrowing of the treated coronary lesion, a process called restenosis. The events that constitute restenosis appear to be a universal response to the arterial wall injury of angioplasty. They are currently characterized as follows: platelet adhesion and aggregation on the damaged endothelium and within deep splits into the tunica media; release of platelet derived growth factors; inflammation of the mechanically injured medial zone; transformation of smooth muscle cells of the tunica media after their activation by several of the growth-promoting substances; migration and proliferation of transformed smooth muscle cells, with secretion of copious amounts of extracellular matrix material; and, finally, termination of the growth process with regrowth of endothelium over the injured area. A decade of research work has helped identify clinical correlates of restenosis after coronary angioplasty procedures. This work is hindered by lack of a uniform angiographic definition of restenosis. In addition, much of the information has come from small studies, with incomplete follow-up and retrospective orientation. Nevertheless, some data are available. Patient-related correlates include male gender, unstable angina, diabetes, and continued smoking after angioplasty. Lesion-related correlates include multilesional and multivessel procedures, higher postangioplasty residual stenosis, proximal vessel location, location in the left anterior descending artery, location in a vein graft, long lesions, and total occlusions. The only consistent procedure-related correlate has been incorrect sizing of the angioplasty balloon to the treated artery. For the purposes of individual patient care, clinical correlates are not helpful. No group of variables has been found to be associated with complete freedom from restenosis, and no group is completely predictive of restenosis. All patients undergoing angioplasty procedures require some follow-up through subsequent months and years. Symptom status and the results of noninvasive studies have been investigated for purposes of follow-up. Symptoms are virtually useless by themselves for predicting restenosis or its absence. When symptom status is combined with exercise thallium 201 scintigraphy performed 4 to 6 months after an angioplasty procedure, the two factors are less than ideal but have a negative predictive value of more than 90%. This means that more than 90% of patients who have neither symptoms nor evidence of ischemia by thallium 201 scintigraphy will not have angiographic restenosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8359110 TI - [The diagnosis and differential diagnosis of Crohn's disease and ulcerative colitis by hydrocolonic sonography]. AB - As part of a prospective study the value of hydrocolonic sonography in the diagnosis and differential diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was assessed and compared with that of coloscopy as standard reference. Of 440 patients who were examined, 41 (23 men, 18 women; mean age 25 +/- 6 years) had CD and 36 (20 men, 16 women; mean age 32 +/- 8 years) had UC. CD and UC were correctly diagnosed by hydrocolonic sonography in 39 and 33 cases, respectively (sensitivity 95 and 91%, specificity 100 and 99%, respectively). Among healthy subjects five layers of variable echo density were demonstrated in the intestinal wall, while in all those with CD the wall was clearly thickened and in 36 of them the wall structure was also abnormal. In 16 patients the wall structure was homogeneous without evidence of layers and in 20, layers 1-3 were not demonstrable and layers 4 and 5 only rudimentary. In contrast, the 33 patients with UC diagnosed by hydrocolonic sonography had only slight thickening of the intestinal wall and all layers were present in 30 of them. CD and UC were correctly distinguished in 91%. Hydrocolonic sonography makes it possible to demonstrate in detail the structural changes in the intestinal wall in CD and UC so that the two conditions can be distinguished. PMID- 8359111 TI - [An increase in cardiopulmonary exercise tolerance after the embolization of a pulmonary arteriovenous fistula]. AB - A 21-year-old woman suffering from increasing dyspnoea on intense physical exercise, was found to have a congenital right-sided arteriovenous pulmonary fistula. This was successfully and without complication embolized using a percutaneously introduced Gianturco wire coil. All symptoms disappeared after this procedure. Definite improvement in physical performance, in comparison with pre-embolization values, was documented by spiroergometry as early as two days later (oxygen uptake 1855 vs. 1459 ml/min; anaerobic threshold 920 vs. 790 ml/min; oxygen-pulse 10.6 vs. 8.0 ml/beat; oxygen partial pressure 77.5 vs. 67.6 mmHg; alveolar arterial oxygen difference 33 vs. 44 mm Hg). Further constant subjective and objective improvement in physical performance was demonstrated 3 months after embolization. This case confirms that embolization of a pulmonary arteriovenous fistula can rapidly achieve lasting improvement in exercise performance. PMID- 8359112 TI - [The diagnostic value of shoulder arthroscopy]. PMID- 8359113 TI - [The diagnosis and therapy of immunologically mediated polyneuropathies]. PMID- 8359114 TI - [The right of the chief physician to inspect his personal file. The judgement of the Federal Labor Court of 8 April 1992]. PMID- 8359115 TI - [Hilus amputation]. PMID- 8359117 TI - [The transmission of myeloid leukemia by preserved blood]. PMID- 8359116 TI - [Thrombosis recurrence in pregnancy]. PMID- 8359118 TI - [The treatment of Candida peritonitis during peritoneal dialysis]. PMID- 8359119 TI - [Gallbladder poly]. PMID- 8359120 TI - [The therapy of Lyme borreliosis]. PMID- 8359121 TI - [The "important physician"]. PMID- 8359122 TI - [Complications following ambulatory liver biopsy]. PMID- 8359123 TI - Retirement plan investment strategies for fiftysomething investors. PMID- 8359124 TI - Discrimination: individual rights vs. mandated behavior. PMID- 8359125 TI - Potentials recorded from neck and supraclavicular fossa during a rapid voluntary contraction of the triceps brachii muscle. AB - Two experiments were performed in order to study whether it is possible to record potentials related to the voluntary movement from electrodes placed on the skin overlying the spinous process of the 2nd and 6th cervical vertebrae and at Erb's point ipsilateral to the movement. In the first series of experiments (Experiment I) the subject initiated spontaneously an arm movement accompanying a contraction of the right triceps brachii muscle. Rapid extension of the right 5 fingers was also performed self paced. Recordings of the potentials were referential to the left knee. The morphology of the potentials from the neck and Erb's point did not differ among time constants, between experimental days, among subjects and between the arm movement and the finger movement. A negative deflection of the cervical potential started preceding the onset of the electromyogram (EMG). This negativity was followed by a positive deflection after the EMG onset. The positive potential was followed by a negative deflection during the rising phase of the EMG. In the second series of experiments the subject performed both reaction and self-paced arm movements. The prime mover was the same as the agonist in Experiment I. Morphology of the potentials recorded with monopolar and bipolar derivations did not differ between the differently initiated movements and among the subjects. The morphology of the potentials from the neck and Erb's point was the same as the morphology of the potentials recorded in Experiment I. The present results indicate that it is possible to record the potentials related to the voluntary movement from neck and supraclavicular fossa. PMID- 8359126 TI - Usefulness of motor evoked potentials in compressive myelopathy. AB - Motor Evoked Potentials elicited by transcranial magnetic stimulation were recorded from 1 degree Dorsal Interosseus for the upper limbs and from Extensor Digitorum Brevis for the lower limbs in 42 subjects with compressive myelopathy (36 in the cervical region and 6 in the dorsal region), radiologically defined by Nuclear Magnetic Resonance (NMR) imaging, with no clinical and radiological signs of radiculopathy. Central motor conduction abnormalities in the cortex-C8 and cortex-L5 tract were compared with clinical signs of motor impairment and with NMR findings. The subjects with medullar hyperintensity of NMR signal at the compression site level, showed a central conduction time (C.C.T.) prolongation in at least one side in the 70% of cases in the cortex-C8 tract and in the 95% of cases in the cortex-L5 tract, while in the cases with no compression site alterations of signal, C.C.T. abnormalities were observed only in 25% in the cortex-C8 tract and in 42% in the cortex-L5 tract. In 12 subjects (10 with cervical compression and 2 with dorsal compression) we compared Motor Evoked Potentials before, two weeks and two months after surgical decompression. The C.C.T. cortex-C8 and cortex-L5 improved at least in one side in 11 out of the 12 subjects, showing a good correlation with clinical recovery. In the examined patients we found a latency reduction statistically significant between the first and second investigation, with a trend to stabilization in the following controls. PMID- 8359127 TI - Recruitment patterns in the cervical paraspinal muscles during cervical forward flexion: evidence of cervical flexion-relaxation. AB - The phenomenon of lumbar paraspinal flexion-relaxation has been well established and its clinical significance to low back pain has been demonstrated. Conversely, cervical paraspinal flexion-relaxation has not been consistently observed. This may be attributable to the inappropriate use of trunk flexion motion used to observe the phenomenon in previous studies. This investigation reports on the observance of cervical flexion-relaxation when flexion is limited to the cervical spine. Results demonstrate the observance of cervical flexion-relaxation in ten of ten asymptomatic subjects when flexion is limited to the cervical region in the seated orthograde position. PMID- 8359128 TI - Electromyography of walking in obese children. AB - The electromyographic activity of six lower extremity muscles during three speeds of walking was examined in fourteen (14) (10 obese and 4 normal weight) pre pubertal children aged 8.5-10.5 years. Ensemble average EMG patterns of six lower extremity muscles at three speeds of walking were compared in obese pre-pubertal and normal weight children. The pattern of EMG activity and phasic characteristics did not change appreciably across the three speeds of walking for either group. The lack of significant change in EMG amplitude with altered speed of walking was contrary to the results of previous studies. Studies involving different weight groups and analyses that involve walking over greater distances are required to provide an alternative data base to normal weight children. PMID- 8359129 TI - Similarity in shape, timing and amplitude of H- and T-reflex potentials concurrently recorded along the broad skin area over soleus muscle. AB - Variations in shape, timing and amplitude of both mono- and bipolarly measured H- and T-reflex potentials can be influenced to a great extent by the muscle architecture and the peculiarities of the extracellular potential field. The "best point" for bipolar measurements, where the amplitude of the bipolar H- and T-potentials is maximal, occurred for the various subjects at a distance of 3.0 to 5.0 cm below the insertion of the gastrocnemii on the Achilles tendon. In contrast, the corresponding "best point" for monopolar H- and T-potentials is located 5.0 to 9.0 cm below the gastrocnemii insertion. The shape, total duration and timing of H- and T-potentials, concurrently measured at the various points along soleus muscle are similar. When the amplitude of the monopolar H- and T potentials are levelled at the "best point" for monopolar measurements, the changes in the amplitude of both sets of potentials, monopolarly and bipolarly measured along soleus muscle, are identical. These results imply similar efferent outputs for both H- and T-reflexes, i.e. recruitment of motoneurons of comparable size. PMID- 8359130 TI - Impaired activation pattern in antagonistic elbow muscles of patients with spastic hemiparesis: contribution to movement disorder. AB - Surface electromyographic "EMG" activity in biceps brachii (agonist muscle) and triceps brachii (antagonist muscle) as well as the discharge behaviour of motor units "MUs" (needle recording) in biceps brachii muscle were recorded during slow (0.33 Hz) and fast (0.66 Hz) voluntary elbow flexion movements (auditory matching task) in fifty patients with spastic hemiplegia. In the spastic limbs, a long lasting, small amplitude tonic co-contraction of antagonist muscles was seen during slow flexions (SF) in 29 cases. This effect was strongest during the fast elbow flexion movements (FF). In 33 patients a triphasic pattern of muscle activation was observed on the unaffected side but not on the spastic side. The amplitude of the agonist surface EMG was significantly reduced and the amplitudes of the MU potentials recruited during maximal effort were generally smaller on the spastic side compared to the unaffected side. The agonist-antagonist activation pattern was analysed with respect to three clinically identifiable functional recovery stages of voluntary movements in the spastic limbs, namely synergistic, isolated and useful movements. The MU amplitudes and the amplitude of the surface EMG activity in the agonist muscle recorded during FF movements became significantly larger whereas the amplitude of the antagonist tonic activity became smaller with increasing functional recovery of the limb. It is concluded that impaired recruitment of type II motor units in the agonist muscles and the inability to selectively activate the agonist muscle contribute to the deficit in motor performance in spastic paresis. PMID- 8359131 TI - Functional anatomy of the hand. AB - The emphasis of this review is on anatomy as related to function of the hand. We have described all aspects of functional anatomy from the skin to the skeletal framework. This article provides a concise overview of the hand and intricacies. PMID- 8359132 TI - Evaluation of the injured hand. AB - Hand disorders are common emergency department problems. They may be associated with long-term disability and significant financial impact for the patient and society. In many areas of clinical medicine, highly technical diagnostic and therapeutic modalities have taken center stage. In contrast, an accurate history and carefully performed physical examination of the hand retains a central and pivotal role in hand evaluation and treatment. PMID- 8359133 TI - Hand infections. AB - Special approaches are required for management of infected wounds involving the hand. Care must be taken to consider involvement of joint, bone, and tendon, or tendon sheath as well as deep fascial spaces. The hand is also prone to infections with unusual microbiology that can result from animal and human bites as well as soil, plant, and water exposures. The special anatomic and microbiologic considerations are critical for selection of proper surgical and medical therapy to preserve function of this vital structure. PMID- 8359134 TI - Flexor tendon injuries of the hand. AB - Flexor tendon injuries can be problematic injuries from the time of occurrence until the patient returns to full and complete recovery. There are many misadventures that can occur along the way. The emergency physician must be keenly aware of the anatomy involved, and a careful history and physical examination must be performed. The diagnosis may be obvious or subtle, and the emergency physician must methodically search for the unsuspected injury. An appropriate referral should be initiated soon after an injury is determined. The hand surgeon has many considerations and obstacles in flexor tendon repairs, but good to excellent results can be expected in up to 80% of patients if the emergency physician and the hand surgeon work together to ensure an optimal patient outcome. PMID- 8359135 TI - Extensor tendon injuries of the hand. AB - Extensor tendon injuries are often initially evaluated and diagnosed in the Emergency Department. These injuries may be painfully obvious or frightfully subtle, but if the emergency physician has a firm understanding of the anatomy involved and he or she embarks on a careful and complete history and physical examination, the diagnosis should be made. There are various considerations in the ultimate treatment and outcome for the patient, and the patient's best interests are served when the emergency physician provides the initial appropriate treatment and proper disposition. PMID- 8359136 TI - Nerve injuries in the hand. AB - Nerve injuries of the hand are an important problem for the emergency physician because most are diagnosed in the emergency setting. Successful diagnosis and treatment are critical if the injured patient is to regain full hand function. Emergency department management relies on the knowledge of hand and forearm functional anatomy and techniques for diagnosing loss of nerve function. Once a nerve injury has been diagnosed, issues such as primary versus secondary repair must be discussed with the hand surgeon. The hand surgeon must consider whether to pursue an epineurial or fascicular repair and must use additional techniques for diagnosing return of nervous function. Lack of nerve regeneration, chronic paresthesias, neuromas, and sympathetic dystrophy can complicate the successful return of hand nerve function after injury. PMID- 8359137 TI - Metacarpal and phalangeal fractures. AB - Metacarpal and phalangeal fractures are common presenting injuries in many emergency departments. The emergency physician should become skilled at properly evaluating and initiating appropriate management and follow-up for these injuries when they occur. Failure to properly do so may result in permanent disability. PMID- 8359138 TI - Wrist fractures. AB - The various types of wrist fractures are described. Keeping in mind the anatomy and biomechanics of the wrist assists in the detection of these injuries. The clinical and radiographic findings are discussed and the various associated injuries that may go undiscovered without maintaining a high index of suspicion. PMID- 8359139 TI - Ligamentous wrist injuries. AB - The wrist is one of the most complex joints of the body. Wrist injuries are quite common, yet improper diagnosis of ligamentous injuries as simply 'sprains' often occurs. Understanding the functional anatomy and mechanics of the wrist is extremely important in appreciating the spectrum of injuries that occur there. A review of the analysis and detection of potential injuries is provided. PMID- 8359140 TI - Amputations and replantations. AB - Essential aspects of emergency department assessment and initial treatment of patients with traumatic amputations are outlined. Pitfalls of early treatment and indications for replantation are discussed. The dogmatic approach is avoided. PMID- 8359141 TI - Fingertip and nail bed injuries. AB - Nail bed and fingertip injuries are commonly seen in the Emergency Department. Each of these injuries must be evaluated carefully not only for the acute situation but for the possible long-term effects. Nail bed injuries must be appropriately diagnosed and treated initially because a secondary repair is often unsatisfactory. Fingertip injuries must provide the patient with a sensitive fingertip with sufficient length for effective use of the finger. The initial care and treatment are vital for the best patient outcome. PMID- 8359142 TI - Special injuries of the hand. AB - Unique injuries resulting from high-pressure injection, wringer washers, cornpickers, and snowblowers are presented. Epidemiology, pathophysiology, clinical presentation, and management are reviewed. These injuries commonly require surgical intervention. Prompt recognition and treatment can greatly influence prognosis. PMID- 8359143 TI - Acute joint injuries of the hand. AB - The joints of the hand are stabilized by articular contours, tough ligamentous structures, and dynamically by a system of flexor and extensor tendons. Disruption of a joint seriously reduces the ability of the hand to function properly. The history and especially a detailed description of the mechanism of injury is invaluable information for the diagnosis and for the ability to anticipate complications. Radiographic evaluation is required for virtually all potential injuries. Multiple views and especially a true lateral view of the digit, when appropriate, are usually sufficient. The clinical examination includes the evaluation of (1) deformity, (2) swelling, (3) tendon and neurovascular status, (4) tests for stability, and (5) active and gentle passive range of motion. The most important aspect of treatment is the ability to distinguish between injuries that require surgery and those that can be splinted and referred for follow-up. In general a near full range of active motion indicates joint congruity, and the injury can be treated by splinting and referral to a hand surgeon. PMID- 8359144 TI - Emergency department treatment of hand burns. AB - The hand burn, although small, can cause significant loss for the patient. Therefore, decisive attention to preserve the skin and the function of the fingers is required. This article reviews assessment of burn injuries, types of burn injuries, and treatment. Pain management information is provided along with recommended antibiotic regimens. Criteria on admission versus outpatient treatment, which is particularly relevant for the emergency physician, is also presented. PMID- 8359145 TI - Conformational properties of the -35 region of the trp promoter in solution: comparison of the wild-type sequence with an AT transversion. AB - The majority of the 1H NMR resonances of the protons in a tetradecamer containing the -35 region of the trp promoter d(GCTGTTGACAATTA): d(TAATTGTCAACAGC) and in the TA transversion have been assigned. The conformational properties of the nucleotides have been determined and compared in the two duplexes. Analysis of spin-spin coupling and NOEs shows that all sugar puckers are in the south domain (i.e. near C2' endo) and the glycosidic torsion angles are anti (chi approximately 110 degrees). The NMR data are consistent with the duplex being in the B family of conformations. Significant differences in chemical shifts between the two molecules were observed only for nearest neighbours to the transversion site, suggesting the absence of long range conformational effects. This was confirmed by the similarity of coupling constants and NOEs. Other properties are also not greatly affected at positions more than two base pairs from the mutation site. These results are consistent with the hypothesis that unconstrained oligonucleotides are highly flexible, and can readily accommodate significant perturbations of the local structure, such as a transversion. PMID- 8359146 TI - Structure of clathrin-coated vesicles from small-angle scattering experiments. AB - Previously published small-angle neutron and X-ray scattering data from coated vesicles, reassembled coats, and stripped vesicles have been analyzed in terms of one common model. The neutron data sets include contrast variation measurements at three different D2O solvent concentrations. The model used for interpreting the data has spherical symmetry and explicitly takes into account polydispersity, which is described by a Gaussian distribution. A constant thickness of the clathrin coats is assumed. The fitting of the model shows that the coated vesicles consist of a low-density outer protein shell (clathrin) and a central protein shell (accessory polypeptides and receptors) of approximately six times higher density. For the X-ray scattering and neutron contrast variation data, the polydispersity of the samples is of the order of 90 A (full-width-at-half-maximum value) and the average outer radius is approximately 400 A. The inner high density shell has inner and outer radii of 115 and 190 A, respectively. A simultaneous fit to the three neutron contrast variation data sets identifies the lipid membrane with a thickness of 40 A and an outer radius of 196 A. Thus, the membrane and the high-density protein shell overlap in space, which shows that the lipid membrane contains protein. The molecular mass of the average particle is 27 x 10(6) Da. The coated vesicles consist, on average, of approximately 85% protein and 15% lipids. About 40% of the protein mass is situated in the central high-density shell, which gives a large amount of protein in the lipid membrane. The densities of the central shell and the lipid membrane show that the hydration is small in the central region. A comparison of the total mass, the mass distribution, and the structure of the average-size particles with the barrel structure shows that the accessory polypeptides are incorporated in the lipid membrane. The results from the neutron data for the reassembled coats show that the structure of these particles is very similar to the structure of the native coats. The main difference is a higher density of the central protein shell, which shows that the membrane is replaced by protein in the reassembled coats. PMID- 8359147 TI - The existence of non-axisymmetric bilayer vesicle shapes predicted by the bilayer couple model. AB - The existence of non-axisymmetric shapes with minimal bending energy is proved by means of a mathematical model. A parametric model is used; the shapes considered have an elliptical top view whilst their front view contour is described using Cassini ovals. Taking into account the bilayer couple model, the minimization of the membrane bending energy is performed at a constant membrane area A, a constant enclosed volume V and a constant difference between the two membrane leaflet areas delta A. It is shown that for certain sets of A, V and delta A the non-axisymmetric shapes calculated with the use of the parametric model have lower energy than the corresponding axisymmetric shapes obtained by the exact solution of the general variational problem. As an exact solution of the general variational problem for non-axisymmetric shapes would yield even lower energy, this indicates the existence of non-axisymmetric shapes with minimal bending energy in a region of the V/delta A phase diagram. PMID- 8359151 TI - Micronucleus test and erythropoiesis: effect of cobalt on the induction of micronuclei by mutagens. AB - The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by cobalt dichloride pretreatment. Cobalt dichloride was used to induce erythropoietin, a growth factor for erythropoiesis. The increase in mutagen induced micronucleus response following cobalt pretreatment, therefore, may have been due to a change in the rate of erythropoiesis. The greatest interaction between cobalt pretreatment and mutagen treatment for the induction of micronucleated polychromatic erythrocytes (MPCE) occurred when mice were injected with 1,1-dimethylhydrazine (DMH) 12-24 hr after pretreatment with cobalt dichloride and killed 30 hr later. Increased sensitivity of the micronucleus test was attributable to the administration of mutagen during the differentiation and multiplication of erythroblast, which is presumed to have been accelerated by pretreatment with cobalt dichloride. An increased induction of MPCE in the bone marrow by two chemicals--benzo(a)pyrene, 2-naphthylamine--was also observed following pretreatment with cobalt dichloride. PMID- 8359152 TI - Investigation of aneuploidy induction in mouse oocytes following exposure to vinblastine-sulfate, pyrimethamine, diethylstilbestrol diphosphate, or chloral hydrate. AB - The various causative and mechanistic phenomena associated with aneuploidy induction require considerable investigation to better understand the etiology of chromosome missegregation. We investigated the potential of vinblastine sulfate, pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate to induce numerical and structural chromosome changes in female mouse germ cells. Superovulated ICR mice were administered the compounds either by intraperitoneal injection or oral gavage, and oocytes were collected and processed for cytogenetic analysis 17 hr later. Vinblastine sulfate, administered i.p., induced a significant increase in the frequency of ovulated MI oocytes and of hyperploid MII oocytes compared to controls, but did not increase the frequency of structural aberrations. Pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate did not increase the frequency of numerical or structural chromosome changes in female mouse germ cells. PMID- 8359153 TI - Genotoxic activity detected in soils from a hazardous waste site by the Ames test and an SOS colorimetric test. AB - Ten soil samples from a hazardous waste site were compared for their genotoxic activity by the Ames test (Salmonella reverse mutation assay) and a modified SOS colorimetric test. Polynuclear aromatic hydrocarbons known to produce frameshift mutations were found in high levels in the soils. Salmonella typhimurium TA98, sensitive to frameshift mutations, was selected as the Ames tester strain. Escherichia coli K12 PQ37 (sulA::lacZ) was the SOS tester strain. Organic extracts were prepared from the soil samples by Soxhlet extraction. One set of the soil samples was extracted with methylene chloride and a second set with cyclohexane. Two criteria from reproducible dose-related increases in response to the soil were used to compare the positive responses: 1) the concentrations required for doubling responses and 2) a minimum concentration required to produce statistically significant increases from background controls. Analysis of variance indicated that with S9 mix, Ames and SOS results were similar for the same soils and solvent extractions. However, without S9 mix, the SOS test was significantly more sensitive than the Ames test to the genotoxins extracted from the soils. Both the Ames and SOS tests detected lower concentrations of genotoxins in methylene chloride than in cyclohexane extracts. The simplicity of the method, reduction in expenses, and results within 1 working day all contribute to the advantages of the SOS test. PMID- 8359154 TI - Chemico/biological investigation of contaminated sediment from the Hamilton Harbour area of western Lake Ontario. AB - Highly contaminated sediment from the Hamilton Harbour area of western Lake Ontario was examined using a bioassay-directed fractionation methodology. A sediment sample was extracted using a Soxhlet apparatus and the resulting extract was fractionated into compound classes using an alumina clean-up step and high performance liquid chromatographic techniques. The resulting fractions were subjected to bioassays using TA98- and TA100-like strains modified by the inclusion of genes for the activating enzymes nitroreductase and O-acetyl transferase. The majority of the mutagenic activity displayed by the sample extract was found to be present in the fraction containing the polycyclic aromatic hydrocarbons (PAH). Extracts of the PAH-containing fraction displayed dramatically higher responses with the TA100 type strains with metabolic activation. Further separation of the PAH-containing fraction showed the majority of the biological activity coeluted with PAH having molecular masses of 276, 278, and 302 amu. PMID- 8359155 TI - Molecular analysis of hypoxanthine phosphoribosyl transferase mutants induced by glycidyl 1-naphthyl ether in mouse spleen cells in vivo. AB - Treatment of C57BL/6J mice with an epoxide, glycidyl 1-naphthyl ether (GNE), resulted in an average of a 3.4-fold increase in frequency of 6-thioguanine resistant mutants of mouse spleen T-lymphocytes. In similar experiments with the epoxide trichloropropylene oxide, no increase in mutant frequency was found. To determine the kind and location of mutations in the coding region of the hypoxanthine phosphoribosyl transferase (HPRT) gene, 26 GNE-induced mutants and 17 spontaneous mutants were analyzed by direct sequencing of polymerase chain reaction amplified cDNA. Among the GNE-induced mutants, HPRT cDNA was present in 22, while that from 4 could not be detected. Among the spontaneous mutants, HPRT cDNA was present in 15 and absent in 2. Among GNE-induced mutants, base substitution in HPRT occurred in 15 of 22 mutants analyzed. Nine of 15 base substitutions involved TA base pairs, primarily TA-->CG transitions. Base substitutions were found throughout exons 3-7 but 46% of substitutions were located in exon 3 and one frameshift mutation involving a GC base pair in exon 3 was also observed. Among the spontaneous mutants, base substitutions of HPRT occurred in 7 of 15 mutants analyzed with 6 of 7 base substitutions involving a TA base pair and another 2 of the 15 mutants showed a 4 base pair deletion. The base substitution spectrum in GNE-induced mutants was different from that of the spontaneous mutants. PMID- 8359156 TI - AMESFIT: a microcomputer program for fitting linear-exponential dose-response models in the Ames Salmonella assay. AB - The Ames Salmonella/microsome assay remains the most widely used microbial test for genotoxicity. In this article, we describe a microcomputer program developed to fit a linear-exponential dose-response model to Ames assay data for established mutagens. The model includes a linear term to describe the mutagenic effects of the test agent at low to moderate doses and an exponential attenuation factor to accommodate downturns at high doses due to cytotoxicity. Quasi likelihood methods are used to obtain estimates of the unknown model parameters, thereby avoiding the need to fully specify the distribution of the experimental data. This method of estimation also allows for extra-Poisson variation that is characteristic of counts of mutant colonies of bacteria observed in the Ames assay. The particular linear-exponential model used here was developed for use in the analysis of a recent large-scale collaborative trial using the Ames assay sponsored by the International Programme on Chemical Safety. The use of our program is illustrated using sample data sets taken from that collaborative study. PMID- 8359157 TI - Dose-dependent genotoxic effects of styrene on human blood lymphocytes and the relationship to its oxidative and metabolic effects. AB - Although the genotoxic potential of styrene is known, very limited information is available regarding its dose-dependent genotoxic response to human blood lymphocytes and how such response correlates with different metabolic events in whole blood lymphocytes. The present study was therefore carried out to study such a relationship using in vitro human blood lymphocytes from healthy volunteers. To study genotoxic response to styrene, sister chromatid exchanges (SCEs), cell cycle, and cell survival were analyzed. Lymphocytes were cultured for 72 hr in the presence of different concentrations of styrene (0-1,000 microM). Twenty-four hr before harvest, BrdU (5 micrograms/ml) was added to assess the increase in SCEs and cell cycle delay. Both the SCE frequency and the cell cycle length were increased linearly with increasing concentrations of styrene up to 200 microM, without addition of any exogenous metabolizing system. Above 200 microM, no further increase in genotoxic response occurred. The range of concentrations (10-200 microM) at which increase of cell cycle length due to styrene was observed did not impair the viability of the cells, suggesting that such cell cycle delay is a genotoxic-related event and not caused by cytotoxicity. In vitro metabolic transformation of styrene in whole-blood lymphocyte cultures without the presence of any exogenous metabolic activation system showed the formation of a reactive intermediate, styrene 7,8-oxide, to be capacity-limited, as verified from a nonlinear increase in the formation of styrene glycol. The value of such metabolic parameter reached a plateau above 200 microM styrene. The same phenomenon of saturation has also been observed with regard to other metabolic effects due to styrene in whole blood lymphocytes in culture, such as dose-dependent increase in lipid peroxidation and depletion of blood lymphocyte glutathione. Based on the relationship between the formation of different metabolic events and the genotoxicity of styrene, it may be possible that the genotoxic properties of styrene in human blood lymphocytes may be mediated initially not only by the formation of the presumably reactive styrene 7,8-oxide, but also by that of a reactive oxygen species as well. However, the present data are not sufficient enough to definitely identify the role of reactive oxygen species in such toxicity and therefore it warrants further study. PMID- 8359158 TI - In vitro and in vivo assays of isopropanol for mutagenicity. AB - To assess the mutagenic potential of isopropanol, an in vitro Chinese hamster ovary (CHO) cell/HGPRT gene mutation assay and a bone marrow micronucleus study in mice were conducted. In the CHO/HGPRT assay, concentration levels ranged from 0.5 to 5.0 mg/ml. No elevated mutant frequencies attributable to treatment were observed in the test under either activated or non-activated conditions. In the micronucleus assay, mice were injected intraperitoneally (IP) with either 350, 1,173, or 2,500 mg/kg of isopropanol at constant volumes of 10 ml/kg. No increased incidence of micronuclei was observed in bone marrow polychromatic erythrocytes (PCEs) harvested at 24, 48, or 72 hr post-dosing. In both assays, negative and positive control mutant frequencies were within historical control ranges. These results, in conjunction with previously published data, clearly demonstrate that isopropanol is not a mutagen. PMID- 8359159 TI - Increasing problems in the therapy of enterococcal infections. PMID- 8359160 TI - One year follow-up study to assess the prevalence and incidence of Lyme borreliosis among Dutch forestry workers. AB - A one-year serological and clinical follow-up study was conducted to assess the prevalence and incidence of asymptomatic and symptomatic infection with Borrelia burgdorferi among 151 Dutch forestry workers. The prevalence of antibodies to Borrelia burgdorferi among the forestry workers and among office employees as control group was compared. Antibodies to Borrelia burgdorferi were detected by enzyme immunoassay. Forestry workers were examined physically at the start of the study. Clinical follow-up of forestry workers whose first blood sample was positive and of persons showing seroconversion was done by telephone interview. If Lyme borreliosis was suspected, clinical and laboratory data were obtained. The seroprevalence was significantly higher among forestry workers (28%) than among controls (5%). Of 127 forestry workers who were examined, 7 (18%) of the 39 seropositive persons but none of the seronegative persons had a history of Lyme borreliosis. None of 32 asymptomatic seropositive forestry workers had developed Lyme borreliosis one year later. The incidence of infection with Borrelia burgdorferi as demonstrated by seroconversion among 95 initially seronegative forestry workers was 5%. None of them had Lyme borreliosis. Infection with Borrelia burgdorferi among forestry workers is frequent but seems to take a benign course. PMID- 8359162 TI - Multicentre evaluation of a biphasic culture system for recovery of mycobacteria from clinical specimens. AB - A new biphasic system (MB Check, Roche) for isolation of mycobacteria from clinical specimens was evaluated by eight different microbiological laboratories in comparison with methods routinely used in the respective laboratories. Altogether 1125 clinical specimens were processed; pretreatment, if performed, was by a variety of methods. Mycobacteria were recovered from 167 specimens with the biphasic system and 165 specimens with the other methods. The average time required for isolation of Mycobacterium tuberculosis was 22.6 days with the biphasic system and 24.7 days with egg-based media; for other mycobacterial species it was 23.5 versus 20.8 days. The inclusion of a chocolate agar section in the biphasic system facilitated the early detection of contaminants, while the NAP-containing section appeared unable to differentiate Mycobacterium tuberculosis from other mycobacterial species. The biphasic system, which enables recovery of mycobacteria in small laboratories without specialized equipment, is more practical than conventional methods and at least as sensitive. PMID- 8359161 TI - Comparison of seven commercial kits for detection of antibodies to Borrelia burgdorferi. AB - Five enzyme immunoassay (EIA) and two Western blot (WB) commercial kits were compared for their ability to detect antibodies to Borrelia burgdorferi. The panel of 53 test sera consisted of 25 sera positive for antibodies to Borrelia burgdorferi, 15 sera negative for such antibodies, 5 sera reactive in serologic tests for syphilis, and 8 sera containing antinuclear antibodies and/or rheumatoid factor. The rate of agreement with reference results was 93%, 90%, 90% and 88% for EIA kits from Diamedix, Cambridge Biotech, Mardx and Sigma respectively. The sensitivity and specificity was 84% and 100% respectively for Cambridge Biotech, 76% and 94% for Diamedix, 68% and 83% for Mardx, and 68% and 83% for Sigma. The three confirmatory tests, Cambridge Biotech WB, General Biometrics P39 EIA and Mardx WB, demonstrated 75%, 60% and 63% agreement respectively. The sensitivity and specificity was 52% and 100% respectively for Cambridge Biotech WB, 24% and 100% for General Biometrics P39 EIA, and 44% and 100% for Mardx WB. The results demonstrate the variable performance of commercial serologic kits for detection of antibodies to Borrelia burgdorferi. WB appears to be a better confirmatory test than the single protein EIA. PMID- 8359163 TI - Immunoglobulin G antibodies to Pseudomonas aeruginosa lipopolysaccharides and exotoxin A in patients with cystic fibrosis or bacteremia. AB - IgG antibodies to nine Pseudomonas aeruginosa lipopolysaccharides (LPS) and exotoxin A in sera from 11 patients with bacteremia and 51 patients with cystic fibrosis (CF) were analyzed. The methods used were enzyme immunoassay (EIA) and immunoblotting. Nine of the 11 bacteremic patients were infected with strains expressing an LPS serotype identical to one of the test antigens. In sera from six of these nine patients, antibody homologous to the serotype of the infecting strain was observed. An antibody response to heterologous Pseudomonas aeruginosa LPS antigens was observed in nine patients. Eight of the bacteremic patients mounted an antibody response to exotoxin A. Thirty-five CF patients chronically colonized with Pseudomonas aeruginosa possessed significantly higher levels of antibody to all of the test antigens than 16 patients with intermittent or no colonization (p < 0.001). For exotoxin A and serotype 3 the sensitivity was 91% and 94%, and the specificity 94% and 88% respectively. When the results for exotoxin A and serotype 3 were combined, the sensitivity was 91% while the specificity was 81%. The pronounced antibody response to heterologous LPS antigens, as measured by the EIA and immunoblot, suggests expression of a common antigen determinant. A simplified serological assay utilizing exotoxin A and serotype 3 as test antigens may be useful for detecting Pseudomonas aeruginosa infections in patients with CF and chronic colonization and in bacteremic patients from whom cultures are not available. PMID- 8359164 TI - Detection of Chlamydia trachomatis in urine from men with urethritis. AB - The performance of a commercial EIA (Chlamydiazyme) for detection of Chlamydia trachomatis in urine specimens was compared with that of culture of urethral samples from men with urethritis. The incidence of chlamydial infection on the basis of culture results was 34% (56/167). The sensitivity, specificity, positive and negative predictive values for the EIA were 55% (31/56), 98% (109/111), 94% (31/33) and 81% (109/134), respectively, compared with culture. Although this EIA has a high specificity, the low sensitivity makes it valueless as a clinical tool for demonstrating chlamydial antigen in urine from men with urethritis. PMID- 8359165 TI - Meropenem versus imipenem/cilastatin in the treatment of intraabdominal infections requiring surgery. AB - In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery. The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease. There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group. Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group. Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from < or = 0.25 to 2 micrograms/ml. At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin. Both antibiotic regimens were well tolerated. PMID- 8359166 TI - Adherence of Corynebacterium urealyticum (CDC group D2) and Corynebacterium jeikeium to intravascular and urinary catheters. AB - The ability of Corynebacterium urealyticum, Corynebacterium jeikeium and other control strains to adhere to two intravascular catheters (polyvinyl chloride and Teflon) and one urinary catheter (Teflon-coated rubber) was studied. Results demonstrated that the Corynebacterium species adhered to all catheter materials in greater numbers than a control strain of Micrococcus luteus (p < 0.001). There was not a clear difference in the ability of the strains of Corynebacterium jeikeium and Corynebacterium urealyticum to adhere to the catheters tested, so that differences other than this property could explain their different pathogenicity for humans. PMID- 8359167 TI - Infection caused by the nonfermentative gram-negative bacillus CDC group IV c-2: case report and literature review. AB - A 10-year-old girl with acute lymphocytic leukemia developed nosocomial septicemia caused by the gram-negative bacterium CDC group IV c-2. Recovery of the patient followed appropriate treatment with ceftriaxone, to which the organism was susceptible in vitro. Four other reported cases of infection caused by this organism are reviewed. PMID- 8359169 TI - Detection of toxigenic Clostridium difficile in fecal samples by colony blot hybridization. AB - A hybridization assay for detection of toxigenic Clostridium difficile in fecal samples was developed and compared with the classical tissue culture cytotoxicity assay. A DNA fragment probe specific for the toxin B gene of Clostridium difficile was synthesized by the polymerase chain reaction and labelled with digoxigenin. Fecal samples were cultured for 24 hours, replica-plated and hybridized with the probe. The hybridization assay had a sensitivity of 100%, specificity of 96.7%, positive predictive value of 86.7% and negative predictive value of 100% compared with the cytotoxicity assay. PMID- 8359168 TI - Use of the polymerase chain reaction to detect Bordetella pertussis in patients with mild or atypical symptoms of infection. AB - Nasopharyngeal aspirates and nasopharyngeal swabs from 177 children exhibiting mild to severe clinical symptoms of whooping cough were tested by the polymerase chain reaction (PCR) and culture for the presence of Bordetella pertussis. In the PCR analysis amplifications of samples prepared with and without DNA extraction were compared. In 26% of samples prepared without DNA extraction, the PCR was found to be inhibited, whereas no inhibition was detected after DNA extraction. Twelve percent (21/177) of the samples were positive in both culture and the PCR, and an additional 49% (87/177) of the samples were positive exclusively in the PCR. Thirty-eight percent (8/21) of culture-positive patients and 63% (55/87) of the patients in whom infection was detected only by PCR had mild or atypical clinical symptoms. Of these groups 26% (5/19) and 50% (39/78), respectively, had been fully vaccinated with three or more doses of diphtheria, tetanus and pertussis vaccine. PMID- 8359170 TI - Analysis of antibiotic resistance determinants in Proteus penneri. AB - The plasmid profiles of 65 strains of Proteus penneri were analyzed to determine whether resistance was determined chromosomally or by plasmids. Only seven strains harboured one to three plasmids, although these strains exhibited resistance to a wide range of antibiotics. Markers for ampicillin and tetracycline resistance could be transferred to Escherichia coli by transformation. Plasmids carried resistance to chloramphenicol in two strains and resistance to sulfonamides in one strain. The result showed that resistance is determined chromosomally rather than by plasmids, however the possibility that these bacteria may acquire resistance plasmids which change their antibiotic susceptibility pattern cannot be excluded. PMID- 8359171 TI - Ampicillin-sulbactam susceptibility testing criteria. AB - In vitro studies in five different medical centers documented the susceptibility of 2,440 consecutive isolates of the Enterobacteriaceae against ampicillin sulbactam disks of different potencies. For determination of MICs, both 2:1 or 1:1 ratios were used as long as the concentrations of sulbactam at the breakpoints remained the same, i.e. MIC < or = 16/8.0 micrograms/ml or < or = 8.0/8.0 micrograms/ml for the susceptible category. Disks containing 10 micrograms of ampicillin and 10 micrograms of sulbactam are still to be preferred with interpretive criteria of > or = 15 mm for susceptible and < or = 11 mm for resistant (MIC > or = 64/32 micrograms/ml or > or = 32/32 micrograms/ml). The reliability of the disk test actually diminished when the amount of sulbactam in the disk was increased. PMID- 8359173 TI - Pulmonary toxoplasmosis in immunocompromised patients. PMID- 8359172 TI - Vibrio alginolyticus wound infection after exposure to sea water in an air crash. PMID- 8359174 TI - Sensitivity to mupirocin of staphylococci isolated from colonized or infected patients in Germany. PMID- 8359175 TI - Group C meningococcal meningitis presenting as acute pericarditis. PMID- 8359176 TI - Systolic time intervals in clinical pharmacology. PMID- 8359177 TI - Renal effects of atrial natriuretic peptide during dopa-decarboxylase inhibition in patients with essential hypertension. AB - To assess whether intrarenal dopamine synthesis could contribute to the renal response to ANP in essential hypertension, the effects of alpha-human ANP infusion (50 ng.min-1.kg-1 b.w. for 30 min) on the urinary excretion of dopamine and sodium, urine flow rate and arterial pressure were evaluated in 7 patients with mild-moderate essential hypertension before (control period) and during DOPA decarboxylase inhibition with carbidopa (carbidopa period). In the control period, urinary dopamine excretion was 400 pg.min-1 in baseline conditions and 340 pg.min-1 during ANP infusion. Carbidopa significantly decreased urinary dopamine excretion both before (210 pg.min-1) and during ANP (99 pg.min-1). In contrast, carbidopa did not affect sodium excretion (control from 184 to 460 mu Eq.min-1; carbidopa period from 140 to 390 mu Eq.min-1) or urine flow rate (control from 5.35 to 11.21 ml.min-1; carbidopa period from 4.29 to 11.54 ml.min 1). Arterial pressure fell significantly during ANP infusion in both periods, and no significant difference was observed between the two study days, i.e. in the absence of and during carbidopa administration. We conclude that DOPA decarboxylase inhibition does not influence the diuretic and natriuretic response to alpha-human ANP infusion in patients with essential hypertension. PMID- 8359178 TI - The effect of different dosage schedules of cisapride on gastric emptying in idiopathic gastroparesis. AB - The aim of this study was to determine the optimal dosage regimen of cisapride for the treatment of idiopathic gastroparesis. We studied 17 patients with documented idiopathic gastroparesis in a three-way, cross-over, double-blind study with three 4-day treatment periods separated by at least 3 days without treatment. In each period, the patients were preloaded with cisapride (10 mg tid) for three days. On the fourth day (the test day) they took either 10 mg or 20 mg before breakfast and placebo before lunch (1 x 10 mg), (1 x 20 mg), or 10 mg before breakfast and 10 mg before lunch (2 x 10 mg). The medications were taken 30 min before meals. Gastric emptying of solids (99mTc-sulphur colloid) was measured at lunch time under basal conditions and during each treatment period. Plasma concentrations of cisapride were determined before the breakfast dose, before the lunch dose, and at 1, 2, 3, 4 and 5 h after. The greatest acceleration in gastric emptying occurred with the 2 x 10 mg regimen. Although the single morning dose of 20 mg also significantly accelerated gastric emptying (P = 0.05), the reduction was not as substantial. Plasma concentrations of cisapride were significantly higher after 2 x 10 mg than after 1 x 20 mg or 1 x 10 mg. There was a significant relation between cisapride plasma concentrations and changes in gastric emptying. Peak concentrations of cisapride greater than 60 ng.ml-1 were invariably associated with acceleration of gastric emptying. We conclude that cisapride 10 mg tid before meals is the optimal dose for the treatment of idiopathic gastroparesis. PMID- 8359179 TI - Effect of quinidine on the interconversion kinetics between haloperidol and reduced haloperidol in humans: implications for the involvement of cytochrome P450IID6. AB - Haloperidol (HAL) is a potent butyrophenone antipsychotic agent which is reversibly metabolized to reduced haloperidol (RHAL). In order to determine if this reversible metabolic pathway is linked to the debrisoquine 4-hydroxylase isozyme of cytochrome P-450 (P450IID6). HAL (5 mg) or RHAL (5 mg) was orally administered to healthy male volunteers in a randomized crossover design both with and without a prior (1 h) oral dose of quinidine (250 mg bisulfate), a potent inhibitor of this isozyme. Thirteen volunteers, 11 extensive metabolizers, 2 poor metabolizers, completed all four phases of the study. Plasma samples harvested over seven days were analysed for HAL and RHAL. An expression for the apparent fractional availability of metabolite from the parent compound given (Fapppm) was derived and was used to determine whether HAL or RHAL is the preferred metabolite, and whether quinidine co-administration alters Fapp for either compound. The AUC (0-t) for both HAL and RHAL were significantly greater following the administration of either compound with quinidine compared with AUC (0-t) values obtained in the absence of quinidine. The maximum plasma concentration (Cmax) of the administered compound was also greater following the administration of quinidine. Quinidine had no effect on the half-lives of the administered compounds. The Fapp for HAL and RHAL were not significantly affected by the administration of quinidine, indicating that the interconversion of HAL and RHAl is not linked to P450IID6. The Fapp of RHAL after administration of HAL was significantly greater than the Fapp of HAL after RHAL administration, indicating that RHAL is the preferred metabolic form. This difference was not affected by quinidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359180 TI - Chlorpromazine in human scalp hair as an index of dosage history: comparison with simultaneously measured haloperidol. AB - The concentration of chlorpromazine (CPZ) in hair was measured to demonstrate its value as an index of individual dosage history and compliance. An animal study using pigmented rats was conducted to confirm the dose-dependent accumulation of CPZ in hair. The concentration of CPZ in hair, newly regrown on a denuded area of the back after the administration of CPZ for 3 weeks, was 4.6, 8.5 and 16.6 ng.mg 1 hair after daily doses of 1.25, 2.5 and 5 mg.kg-1.day-1, respectively, significantly correlated with the daily dose. The concentration of CPZ in black hairs collected from 23 Japanese patients, who had been taking CPZ in fixed daily doses (30-300 mg/day), ranged from 1.6 to 27.5 ng.mg-1, and was significantly correlated both with the daily dose and with the trough plasma concentration at steady state. Several strands of hair collected from each of 5 patients, whose doses of CPZ had been changed within several months before sampling, were cut into 1-cm pieces successively from the scalp end and the concentration of CPZ in each piece was measured. With the assumption of a hair growth rate of 1 cm per month, the individual history of CPZ doses in all patients could be deduced from the distribution of CPZ along the hair shaft. In 5 patients with grizzled hair the concentration of CPZ in white hairs was much lower (< 10%) than in black hairs, suggesting that the strong affinity of CPZ for hair melanin may explain the accumulation of CPZ in black hair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359181 TI - Polymorphic 2-hydroxylation of desipramine. A population and family study. AB - We have studied desipramine hydroxylation capacity, determined as the metabolic ratio of desipramine to 2-hydroxydesipramine in the urine after a single oral dose of 10 mg of desipramine, in 340 Swedish Caucasians, including the members of 45 two-generation families. Desipramine metabolic ratios were bimodally distributed among 237 unrelated subjects and 8% were poor metabolizers. There was a strong correlation between the metabolic ratios for desipramine and debrisoquine in 337 subjects phenotyped with both drugs and there was no dissociation between their capacities to hydroxylate desipramine and debrisoquine. Complex segregation analysis in the 45 families gave evidence for a major locus with incomplete recessivity (d = 0.14) controlling the 2 hydroxylation of desipramine. Similar results were obtained in segregation analysis for debrisoquine. There was evidence for linkage between the CYP2D6 gene and the gene regulating the hydroxylation of desipramine and debrisoquine. This study has provided unequivocal evidence that the capacity to 2-hydroxylate desipramine is polymorphic and under similar genetic control to the hydroxylation of debrisoquine. PMID- 8359182 TI - Comparison of the effects of two different galenical preparations of glyceryl trinitrate on pulmonary artery pressure and on the finger pulse curve. AB - The time course and the magnitude of the effect of glyceryl trinitrate (GTN) on central venous (pulmonary artery diastolic pressure-PAPd) and peripheral arterial (a/b-ratio of the finger pulse wave) haemodynamics were compared in a randomized double-blind cross-over study in 12 patients suffering from congestive heart failure (NYHA II-III) with elevated PAPd at rest (> or = 15 mmHg). The data were obtained in a bioavailability study of two sprays of glyceryl trinitrate, which differed in their galenical characteristics and in the dose of GTN (0.4 mg vs. 0.8 mg). Following sublingual administration of each spray, PAPd, a/b-ratio and the plasma concentrations of GTN and its metabolites were measured up to 30 min. The relative bioavailability of GTN of the test preparation was estimated to be 157%, 161% and 147%, when calculated from the plasma concentration-time data or the integrated effect of GTN on a/b-ratio or PAPd, respectively. The mean time courses of the decrease in PAPd and the increase in the a/b-ratio of the finger pulse curve were mirror images. Thus, there was a strong correlation between the mean values of PAPd and a/b-ratio following the administration of glyceryl trinitrate. Since the slope of the relationship differed considerably between the patients, the magnitude of effect of GTN on PAPd in the individual patient could not be predicted from the changes in a/b-ratio. PMID- 8359183 TI - Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension. AB - To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage. At entry (before placebo), SI was slightly but not significantly lower in group A than B [2.7 vs. 3.6 x 10(-4) ml.microU-4.min-1]; fasting plasma insulin was 13.6 vs. 12.9 microU.ml-1. After 6 weeks on placebo, S1 averaged 3.7 in group A and 4.4 x 10(-4) microU.ml-1.min-1 in group B; fasting plasma insulin was 14.6 vs. 15.1 microU.ml-1, and glucose 5.5 vs. 5.5 mmol.l-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359184 TI - Pharmacokinetics and pharmacodynamics of benazepril hydrochloride in patients with major proteinuria. AB - We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o. The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients. Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42%. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients. In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage. PMID- 8359185 TI - Absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in man. AB - The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i.v. administration the subjects received 4 micrograms dDAVP. For intestinal administration 400 micrograms dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i.v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml.min-1.kg-1, amount excreted in urine 2.0 micrograms and renal clearance was 0.8 ml.min-1.kg-1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02-0.35%). f was 0.24% after duodenal application (range 0.04-0.62%), 0.19% after jejunal (range 0.01-0.41%), 0.03% after distal ileal (range 0.01-0.08%), 0.04% after proximal colonic (range 0.01-0.12%) and 0.04% after rectal (0.01-0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found. PMID- 8359186 TI - Evaluation of the effect of thymoxamine solution 0.5% on mydriasis induced by ibopamine solution 1%. AB - The effects of thymoxamine 0.5% solution and of a placebo solution (mannitol) on the mydriasis induced by ibopamine 1% solution were evaluated in 8 healthy volunteers and 12 patients with eye diseases. One drop of ibopamine was instilled into each eye and 30 min later 1 drop of thymoxamine was instilled into one eye and 1 drop of placebo into the contralateral eye. Pupillary diameter was measured before and 30 min after the instillation of ibopamine, immediately before the treatment with thymoxamine and placebo and 30, 60 and 90 min after the instillation of thymoxamine or of placebo. Within 30 min of treatment, ibopamine had produced a statistically and clinically significant mydriatic effect. In eyes treated with thymoxamine, prompt reversal of mydriasis was observed, the baseline diameter being observed within 60 min. No difference in the time-course of the mydriatic effect was detected between healthy subjects and patients. The pupillary response to thymoxamine was not influenced by the colour of the iris. The tolerability of ibopamine and of thymoxamine was good. No local or systemic adverse events were seen or reported. PMID- 8359187 TI - Plasma protein binding of the enantiomers of hydroxychloroquine and metabolites. AB - The in vitro binding of the enantiomers of hydroxychloroquine and its three major metabolites in pooled plasma obtained from four healthy volunteers and the binding of the enantiomers of hydroxychloroquine to purified plasma proteins has been investigated. The plasma protein binding of hydroxychloroquine was found to be stereoselective. The (S)-enantiomer of hydroxychloroquine was 64% bound in plasma, while (R)-hydroxychloroquine was 37% bound. Fifty% of (S) hydroxychloroquine was bound to a 40 g.l-1 solution of human serum albumin, while only 29% of the (R)-enantiomer was bound. The enantioselectivity of hydroxychloroquine binding was reversed in a 0.7 g.l-1 solution of alpha 1-acid glycoprotein with (R)-hydroxychloroquine being bound to a greater extent than its optical antipode (41% versus 29%). The enantiomers of the metabolites of hydroxychloroquine were bound to a similar extent to plasma and purified plasma proteins. Binding of hydroxychloroquine to plasma and purified proteins was found to be linear over the racemic concentration range of 50 to 1000 ng.ml-1 and hydroxychloroquine metabolite binding to plasma was linear over the range 25 to 500 ng.ml-1. PMID- 8359188 TI - Enalapril related changes in the fibrinolytic system in survivors of myocardial infarction. AB - Disturbances of the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an ACE inhibitor (enalapril) and a placebo on the fibrinolytic system have been compared. Eighty one survivors of acute myocardial infarction were randomised to treatment with enalapril or placebo. The mass concentrations and activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in plasma were measured three months after the infarction. The enalapril group had a significantly lower level of tPA antigen compared to the placebo-treated group (9.2 and 10.6 respectively). There was no difference between the two groups in any of the other fibrinolytic variables. We conclude that survivors of myocardial infarction treated with enalapril have a significantly lower concentration of tPA antigen than those treated with placebo. This may have a prognostic implication, as lower plasma concentrations of tPA antigen have been associated with better prognosis in patients with established coronary heart disease. PMID- 8359189 TI - The effect of age on diurnal variation in the pharmacokinetics of propranolol in hypertensive subjects. AB - There is diurnal variation in the absorption rate of propranolol in younger subjects. This study was undertaken to examine the effect of age on the chronopharmacokinetics of propranolol. We gave 20 mg of propranolol orally to 13 younger and 11 older hypertensive subjects at 09.00 h (day study) or 21.00 h (night study) in a cross-over design. Plasma concentrations of propranolol and its metabolites, 4-hydroxypropranolol and naphthoxylactic acid, were determined just before and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 h after dosage. In the younger subjects the absorption rate constant (ka) of propranolol and its maximum plasma concentration (Cmax) were significantly higher and the time to maximum concentration (tmax) was significantly shorter in the day than at night. There were similar time-variant changes in Cmax and tmax for 4-hydroxypropranolol and naphthoxylactic acid. In contrast, there were no time-variant changes in ka, Cmax and tmax of propranolol and its metabolites in the older subjects. These results suggest that propranolol is absorbed more rapidly after morning dosing than after night-time dosing in younger but not in older subjects. Based on these findings, we speculate that the time-variance in the absorption rate or first-pass elimination, or both, of propranolol diminish with age. PMID- 8359190 TI - Pharmacokinetics and beta-blocking effects of transdermal timolol. AB - The pharmacokinetic profiles of transdermal timolol 6 and 24 mg (as 5 and 20% w/v patches) was studied in four healthy young volunteers. To assess its bioavailability, the pharmacokinetics of an IV infusion of timolol maleate 5 mg was also determined in the same subjects. When the 20% (w/v) timolol patch was applied, the mean bioavailability was 74.4%. Plasma timolol concentrations were below the detection limit when a 5% patch was applied to the same skin area in all four subjects, except for one in whom the bioavailability was 23.6%. Weak erythema developed at the application site in all of the volunteers after application of the 20% (w/v) patch. However, erythema did not develop in any volunteer when the 5% patch was applied. The beta-blocking effect was determined by exercise testing. Similar plasma levels generated similar changes in exercise induced heart rate after the transdermal and intravenous administration of timolol. PMID- 8359191 TI - Pharmacokinetics of nocloprost in human volunteers and its relation to dose. AB - The pharmacokinetics and absolute bioavailability of nocloprost, a synthetic PGE2 analogue with cytoprotective properties, was investigated in human volunteers as a function of the dose. Ten young male volunteers received nocloprost 5 micrograms i.v. and 100, 200 and 400 micrograms p.o. in random order at weekly intervals. Serum nocloprost levels were monitored for up to 12 h after each dose, using a specific, validated assay. After nocloprost 5 micrograms i.v. the highest serum level of 373 pg.ml-1 was found in the first sample 5 min after injection, and the subsequent decline showed one or two phases, with half-lives of 4 and 49 min. The AUC was 89 pg.h.ml-1, the total plasma clearance was 13.2 ml.min-1.kg-1, and the volume of distribution at steady state was 0.16 l.kg-1. After oral administration the maximum serum level and AUC increased in proportion to the dose. tmax showed a wide scatter, with an average value of about 30 min independent of the dose. Although not detectable in every subject, post maximum serum levels declined biphasically, with half-lives of ca 10 and 35-40 min. The absolute bioavailability after oral administration averaged about 2% and was independent of the dose. PMID- 8359192 TI - Absorption of zidovudine in patients with diarrhoea. AB - Many patients with AIDS have gastrointestinal complaints, including the major clinical disorder of chronic diarrhoea. The pharmacokinetics of zidovudine was studied in 9 male patients with HIV infection and diarrhoea to establish whether drug absorption was impaired in them. The peak plasma concentration and AUC after a single oral dose of 200 mg, were the same as those reported in 6 healthy male volunteers (3.1 vs 4.0 mumol.l-1 and 7.2 vs 5.2 mumol.h.l-1, respectively). Since the bioavailability of zidovudine is not particularly impaired, oral zidovudine therapy can be maintained in patients with diarrhoea. PMID- 8359193 TI - Pharmacokinetics of exogenous adenosine in man after infusion. AB - The plasma kinetics of adenosine was investigated in healthy volunteers after a 1 minute infusion of 2.5, 5 and 10 mg (38.79 and 148 micrograms.kg-1 respectively) and after infusion of 200 micrograms.kg-1 in 10 min followed by 400 micrograms.kg 1 in 10 min. As the dose in the 1 min infusion study was increased the mean CL of adenosine decreased (10.7, 4.70 and 4.14 l.min-1, respectively), its mean half life increased (0.91, 1.24 and 1.86 min, respectively), and the mean volume of distribution did not show any clear trend (8-13 l). After the 20 minute infusion the plasma level of adenosine reached a peak value comparable to that observed after infusion of 5 mg in 1 min (about 0.5 micrograms.ml-1), but the mean clearance and half-life were significantly different (12.1 l.min-1 and 0.63 min respectively). In all the subjects the plasma concentration of adenosine had returned to the baseline value in 5-15 min after the end of the infusion. PMID- 8359194 TI - Cefotiam during continuous haemofiltration. PMID- 8359195 TI - Cisplatin, an antineoplastic drug, inhibits catecholamine secretion from bovine adrenal chromaffin cells. AB - Long-term pretreatment (12-120 h) of cultured bovine adrenal chromaffin cells with cis-diamminedichloroplatinum (cisplatin, Pt(NH3)2Cl2) (33 microM), an antineoplastic drug, resulted in a decrease in the secretion of catecholamines from the cells stimulated by acetylcholine. Acetylcholine-induced 45Ca2+ influx into the cells was also reduced in the cells pretreated with cisplatin for 48 h. The concentration-response curves (3-66 microM) for cisplatin inhibition of the secretion and 45Ca2+ influx were quite similar. Pretreatment of cells with 33 microM Pt4+ or carboplatin, an analog of cisplatin, for 48 h also led to a decrease in acetylcholine-evoked secretion, but not with 33 microM Pt2+ or other metals (Au+, Au3+, Ni2+, Os3+, Pd2+, Ir3+, and Ir4+) that have properties similar to Pt4+. These results strongly suggest that in bovine adrenal chromaffin cells, cisplatin (3-66 microM) inhibits catecholamine secretion by the suppression of the Ca2+ influx into the cells evoked by acetylcholine and that the inhibitory effect of cisplatin is attributable to the tetravalent platinum ion in its molecule. PMID- 8359196 TI - Effect of age on vascular content of calcitonin gene-related peptide and mesenteric vasodilator nerve activity in the rat. AB - Effects of age on sensory nerve vasodilator activity and vascular calcitonin gene related peptide (CGRP) levels were investigated in Fischer 344 rats, aged 6, 20 and 27 months. Increases in pressure to transmural nerve stimulation (TNS) of the isolated perfused mesentery were greater at 27 months compared to 6 or 20 at frequencies of 4 and 8 Hz. With guanethidine to block adrenergic nerves and methoxamine to increase smooth muscle tone, TNS-induced vasodilation of the perfused mesentery decreased with age, reaching statistical significance at a frequency of 4 Hz and 27 months. There were no significant differences with age in concentration-response curves to CGRP in the perfused mesentery, except for the oldest rats at low concentrations of CGRP which showed increased vasodilation. Levels of CGRP-like immunoreactivity (CGRP-LI) in mesenteric and femoral arteries at 27 months were significantly less compared with 6 and 20 months; in the renal artery CGRP-LI was significantly decreased by 20 months. This study suggests that decreased sensory nerve function in aging animals may contribute to age-related alterations in circulatory hemodynamics. PMID- 8359197 TI - Recombinant interleukin-5 induces in vivo airway hyperresponsiveness to histamine in guinea pigs. AB - Interleukin-5-producing CV-1 cells were encapsulated in alginate and injected i.p. in guinea pigs (4 x 10(6)/animal). These cells produced approximately 8 ng interleukin-5 per 4 x 10(6) cells per day. Airway hyperresponsiveness to histamine in vivo was observed 3 and 7 days after administration. The increase in lung resistance after intravenous administration of histamine to guinea pigs was significantly potentiated, by approximately 70 to 90% in interleukin-5-treated animals. In animals treated with antibody to interleukin-5, the administration of interleukin-5-producing CV-1 cells did not induce hyperresponsiveness. The percentage of eosinophils in broncho-alveolar lavage fluid was increased by 100% at 7 days but not at 3 days after administration of interleukin-5-producing CV-1 cells. Antibody to interleukin-5 prevented the broncho-alveolar lavage eosinophilia at 7 days after interleukin-5 administration. It can be concluded that interleukin-5 induces broncho-alveolar lavage eosinophilia and airway hyperresponsiveness and that these phenomena do not occur simultaneously. These data suggest a role for interleukin-5 in the development of airway hyperresponsiveness in bronchial asthma. PMID- 8359198 TI - Electrical kindling of rats treated discontinuously or continuously with haloperidol. AB - Intermittent as opposed to continuous treatment of rats with haloperidol resulted in a long-lasting potentiation of oral activity. To examine if this behavioural sensitization to discontinuous neuroleptic treatment facilitates seizure development in electrical kindling, rats treated either intermittently or continuously with haloperidol for 15 weeks were kindled in the nucleus amygdala. Development of kindled seizures was significantly faster in the intermittently treated group (P < 0.01) than in controls or continuously treated rats. Furthermore, discontinuously treated animals displayed electroencephalographic afterdischarges in the substantia nigra from the beginning of treatment. The findings of cross-sensitivity between electrical amygdala kindling and pharmacological sensitization and of early appearance of epileptiform nigral activity have implications for the pathogenesis of both conditions. We suggest that depressed gamma-aminobutyric acid activity in substantia nigra could be a common mechanism. PMID- 8359199 TI - Effects of repeated administration of propentofylline on memory impairment produced by basal forebrain lesion in rats. AB - The effects of repeated propentofylline administration on impairments of learning and memory in rats with basal forebrain lesions were investigated in several behavioral tasks (water maze, habituation and passive avoidance tasks). Rats were subjected to all the tasks in sequence. Basal forebrain lesions produced by bilateral injections of ibotenic acid (approximately 6 micrograms on each side) severely impaired performance in water maze, habituation and passive avoidance tasks. Repeated administration of propentofylline (10 and 25 mg/kg per day for 14 days, p.o.) improved the deficits of performance in a water maze task, even when administration began one week after the basal forebrain lesions were produced. The impaired performance in habituation and passive avoidance tasks was also markedly ameliorated after repeated administration (24 and 26 days) of propentofylline. The rats with basal forebrain lesions exhibited a significant decrease in choline acetyltransferase activity in the cortex. Propentofylline significantly increased hippocampal choline acetyltransferase activity in basal forebrain-lesioned rats compared with that in vehicle-treated basal forebrain lesioned rats. However, cortical choline acetyltransferase activity in basal forebrain-lesioned animals was not affected by repeated propentofylline administration. These results indicate that repeated administration of this agent ameliorated the impaired performance of basal forebrain-lesioned rats in part by increasing hippocampal choline acetyltransferase activity. Propentofylline might be useful for the treatment of amnesia and dementia. PMID- 8359200 TI - Pharmacological properties of ATP-sensitive K+ channels in mammalian skeletal muscle cells. AB - The patch-clamp technique (single-channel recordings) was used to study the effects of glibenclamide and some channel openers on the KATP channel in mouse skeletal muscle. In outside/out membrane patches, glibenclamide reversibly inhibited KATP channel activity in a dose-dependent manner with an apparent Ki of 190 nM. In inside/out membrane patches, RP 61419 increased KATP channel activity both in the absence and in the presence of internal ATP while other K+ channel openers such as nicorandil and cromakalim required the presence of internal ATP to evoke channel activation. The half-maximal activity effect for cromakalim, with 0.5 mM ATP at the cytoplasmic face, was observed at about 220 microM. Pinacidil was unable to activate the KATP channel in the absence of internal ATP and could even reduce channel opening in situations where activity was high in the control. In the presence of internal Mg2+, activation by pinacidil occurred when ATP or low and weakly activating concentrations of ADP were present at the cytoplasmic side. Pinacidil activation could also be observed in the presence of ATP or ADP when Mg2+ was absent from the internal solution. The mechanism of action of pinacidil is discussed in terms of interactions between the different nucleotide regulatory sites and the K+ channel opener binding site of the KATP channel. Half-maximum activation of the KATP channel in the presence of 0.5 mM ATP at the cytoplasmic face was observed at 125 microM pinacidil. PMID- 8359201 TI - Bradykinin is less potent in causing airway microvascular leakage in immature than in adult guinea-pigs. Role of neutral endopeptidase. AB - To study the effect of maturation on bradykinin-induced airflow obstruction and airway microvascular leakage, we measured changes in both lung resistance (RL) and extravasation of Evans Blue dye in anaesthetized immature (aged 12 +/- 1 days) and adult guinea-pigs (aged 77 +/- 2 days). After measurement of RL after i.v. administration of bradykinin (2.5, 5 and 10 nmol/kg) or vehicle (0.9% NaCl), dye extravasation in the lower airways was examined in the same animal. Bradykinin did not cause a significant increase in RL in immature airways, whereas even 2.5 nmol/kg induced a significant elevation in adult airways. Bradykinin-induced extravasation of Evans Blue dye was greater in adult than in immature animals. Phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, did not abolish the age-related difference in the amount of dye extravasated, suggesting that mechanisms other than changes in neutral endopeptidase activity may be responsible for the lower potency of bradykinin in inducing airway microvascular leakage in immature airways. PMID- 8359202 TI - Involvement of vasoactive intestinal polypeptide in gastric reflex relaxation. AB - We have previously presented evidence for a non-adrenergic, vagally mediated colono-gastric inhibitory reflex induced by distension of the colon. We also found that pain stimulation by putting pressure on a testicle induced a pronounced gastric relaxation mediated by both adrenergic and vagal non adrenergic fibres in anesthetized rats. Previous in vitro studies by other workers have strongly indicated that vasoactive intestinal polypeptide (VIP) is a neural mediator of gastric relaxation. The aim of the present in vivo study was to investigate, in anesthetized rats, whether VIP is involved in the gastric reflex relaxation induced by colonic distension and pain stimulation. A volumetric method was used to monitor changes in gastric volume. Gastric reflex relaxation following colonic distension was significantly and markedly inhibited by VIP antiserum as compared to the control relaxation before administration of the antiserum. Non-immunized control serum did not significantly influence gastric relaxation caused by colonic distension. Pain-induced gastric relaxation was moderately but significantly reduced after the administration of VIP antiserum but not after control serum. The selective beta 2-adrenoceptor agonist, salbutamol, induced a pronounced gastric relaxation of the same magnitude before and after the administration of VIP antiserum. VIP antiserum changed the pattern of gastric motility by inducing a specific type of gastric contraction appearing spontaneously or in response to colonic distension. A close intra-arterial injection of VIP induced gastric relaxation and inhibition of phasic gastric contractions. The present results in the rat suggest that VIP or a VIP-like peptide is involved in gastric reflex relaxation induced by colonic distension and pain stimulation. PMID- 8359204 TI - Effect of 5-hydroxytryptamine on glossopharyngeal afferent nerve activity in anesthetized rats. AB - Excitatory responses to 5-hydroxytryptamine (5-HT) were recorded from the whole glossopharyngeal afferent nerve in anesthetized rats, using an electrophysiological technique. Bolus intravenous injection of 5-HT (6.25-50 micrograms/kg) evoked a dose-dependent excitation of glossopharyngeal afferent nerve activity with a rapid onset and lasting a few seconds. This response was blocked by a selective 5-HT3 receptor antagonist, YM060 (10 micrograms/kg i.v.). A 5-HT3 receptor agonist, 2-methyl-5-HT (6.25-50 micrograms/kg), also produced a rapid and dose-dependent excitation of this nerve activity, and YM060 (10 micrograms/kg i.v.) caused an inhibition of this effect. In contrast, efferent glossopharyngeal nerve activity was not altered by 5-HT even at a high dose (50 micrograms/kg). These results suggest that exogenous 5-HT may elicit excitation of the glossopharyngeal afferent nerve, and that this effect might be mediated via the 5-HT3 receptors on the nerve endings. PMID- 8359203 TI - Effects of serotonin and the 5-HT2/1C receptor agonist DOI on neurons of the cerebellar dentate/interpositus nuclei: possible involvement of a GABAergic interneuron. AB - The present study was designed to examine the effects of iontophoretically applied serotonin (5-HT) on neurons of the cerebellar dentate/interpositus nuclei in an in vitro slice preparation and to determine if the 5-HT2/1C receptor subtype could be responsible for mediating any effects noted with 5-HT. 5-HT and the 5-HT2/1C-selective agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were iontophoretically applied alone and during superfusion of the 5-HT2/1C-selective antagonist, ritanserin. 5-HT and DOI elicited either inhibition or excitation of the spontaneous activity of dentate/interpositus neurons. An inhibitory response was induced by both compounds in the majority of cells responding. Ritanserin significantly attenuated the inhibitory response elicited by both 5-HT and DOI. In addition, the inhibitory response to DOI was significantly attenuated by the gamma-aminobutyric acid (GABA) antagonists, bicuculline and picrotoxin. Our results suggest that the 5-HT2/1C receptor subtype may be partially responsible for mediating 5-HT-induced inhibition of dentate/interpositus neurons, possibly via activation of GABAergic interneurons. PMID- 8359205 TI - NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists. AB - In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease. PMID- 8359206 TI - p-chlorophenylalanine-reversible reduction of sigma binding sites by chronic imipramine treatment in rat brain. AB - Repeated treatment with imipramine (10 mg/kg intraperitoneally (i.p.), once daily for 14 days) caused a decrease in the Bmax, without affecting the Kd, of [3H]DTG (1,3-di-o-tolylguanidine) binding to the haloperidol-sensitive sigma sites in the striatum, hippocampus and cerebral cortex of the rat. A similar reduction was observed after chronic administration of a selective serotonin uptake inhibitor, fluoxetine (10 mg/kg i.p., twice daily for 14 days), but not of a selective norepinephrine uptake inhibitor, desipramine (10 mg/kg i.p., once daily for 14 days). Neither a single injection of imipramine (10 mg/kg i.p.) nor addition of imipramine or fluoxetine into the binding assay medium mimicked the changes in the maximal binding of brain sigma sites induced by chronic treatment with these drugs. Finally, depletion of brain serotonin by means of repeated administration of p-chlorophenylalanine, which produces inhibition of the amine synthesis, blocked the ability of repeated imipramine treatment to reduce the maximal number of [3H]DTG binding sites in the striatum and hippocampus. The present results suggest that cerebral serotonergic transmission may play a role in the regulation of cerebral sigma binding sites in the rat. PMID- 8359207 TI - Trifluoperazine inhibition of insulin-induced increase in skeletal muscle glucose uptake. AB - The ability of trifluoperazine, a calmodulin blocker, to prevent increases in skeletal muscle glucose uptake induced by insulin was tested. Insulin significantly increased glucose uptake by the rat hindlimb and trifluoperazine (10(-6) M) completely inhibited this increase. We conclude that calmodulin is a factor involved in the regulation of insulin-mediated glucose transport in muscle cells. PMID- 8359208 TI - Antiproliferative effect of esculetin on vascular smooth muscle cells: possible roles of signal transduction pathways. AB - The effect of esculetin, a coumarin derivative with lipoxygenase inhibitor activity, on the proliferation response of cultured rabbit vascular smooth muscle cells was studied. Proliferation response was determined by the uptake of tritiated thymidine. Esculetin (10(-5)-10(-4) M) dose dependently inhibited the enhanced proliferation stimulated by 5% fetal calf serum. The structure-activity relationship of esculetin and eight other coumarin derivatives indicates that two adjacent phenolic hydroxyl groups at the C-6 and C-7 positions in the coumarin skeleton are necessary for the potent antiproliferative effect. The antiproliferative effects of other lipoxygenase inhibitors, 5,8,11,14 eicosatetraynoic acid (ETYA) and ketoconazole, were comparable to the effect of esculetin. However, esculetin exhibited the greatest maximal suppression. The enhanced releases of 12-hydroxyeicosatetraenoic acid (12-HETE), prostaglandin E2 and 6-keto-prostaglandin F1 alpha in the culture medium of smooth muscle cells stimulated by 5% fetal calf serum were significantly reduced by esculetin. Furthermore, the fetal calf serum-stimulated protein tyrosine kinase activity was reduced by esculetin (10(-5)-10(-4) M) in a dose-dependent manner. In contrast, the protein kinase C activity stimulated by phorbol-12-myristate-13-acetate was not affected by esculetin (10(-6)-10(-4) M). These results suggest that the antiproliferative effect of esculetin on vascular smooth muscle cells may be partly mediated through inhibition of protein tyrosine kinase and modulated by inhibition of lipoxygenase. PMID- 8359209 TI - Enhanced stress-induced dopamine release in the prefrontal cortex of amphetamine sensitized rats. AB - This study examined the extent to which chronic d-amphetamine administration sensitizes animals to some behavioral and neurochemical effects of foot shock stress. Rats received daily injections of saline for 14 days or d-amphetamine (2 mg/kg 7 days and 4 mg/kg 7 days). After a 7 day drug abstinent period, extracellular dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations were measured in the medial prefrontal cortex using in vivo microdialysis in freely moving rats. The behavioral responses to mild foot shock stress were enhanced in the d-amphetamine-pretreated subjects. Concomitant with this behavioral sensitization, d-amphetamine-pretreated subjects showed greater stress-induced increases in extracellular dopamine in the medial prefrontal cortex than in controls. d-Amphetamine (2 mg/kg)-induced stereotyped behavior was also enhanced in the amphetamine-pretreated animals compared to controls; however, d-amphetamine-induced increases in extracellular dopamine in the medial prefrontal cortex were not enhanced in the amphetamine-pretreated group. These results suggest that the mesocortical dopaminergic system is involved in cross sensitization between d-amphetamine and stress, but not in d-amphetamine-induced behavioral sensitization. PMID- 8359210 TI - Endothelin mechanisms in altered thyroid states in the rat. AB - Endothelin (ET) and its receptor characteristics were studied in hyper- and hypo thyroid states in the rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg i.p.) for 8 weeks, while hypothyrodism was induced by daily administration of methimazole (10 mg/kg i.p.) for 8 weeks. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased serum T3 and T4 concentration, blood pressure and heart rate. The chronic administration of methimazole decreased the rate of gain of body weight, serum T3 and T4 concentration, blood pressure and heart rate as compared to vehicle-treated control. Plasma ET-1 levels were found to be similar in control and methimazole-treated rats, while the levels were found to be significantly (P < 0.002) increased in thyroxine-treated rats as compared to control rats. Binding studies showed that [125I]ET-1 bound to a single, high affinity binding site in the cerebral cortex, hypothalamus and pituitary. The density (Bmax) and the affinity (Kd) of [125I]ET-1 binding in the cerebral cortex and hypothalamus were found to be similar in control, methimazole- and thyroxine-treated rats. The pituitary of thyroxine-treated rats showed a decrease in the binding (34.3% decrease in the density) of [125I]ET-1 as compared to control rats. No difference was observed in the binding of [125I]ET-1 to pituitary membranes from control and methimazole-treated rats. Competition studies showed that the IC50 and Ki values of ET-3 for [125]ET-1 binding were about 8 to 11 times higher than ET-1 in cerebral cortex, hypothalamus and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359211 TI - Relationship between scaffold-attached regions, sequences replicating autonomously in yeast, and a chromosomal replication origin in the Drosophila rDNA. AB - The potential relationship between anchorage of Drosophila rDNA to a nuclear substructure and replication mechanisms was studied. First, two scaffold-attached regions (SARs) were identified, in the internally transcribed spacer and in the region spanning both the intergenic spacer (IGS) and the externally transcribed spacer (ETS), respectively. These SARs define two possible loops containing the sequence coding for the 18S rRNA and part of that coding for the 28S rRNA, respectively. They also bind yeast scaffolds. Then, the presence of sequences able to promote extrachromosomal replication in yeast (ARSs) was tested. The identified ARSs comap with SARs. The tight relationship between SARs and ARSs was further investigated in the IGS-ETS region which contains a chromosomal replication origin. The topological correlation observed between SARs, ARSs, and a chromosomal replication origin suggests the physical association of the replication origin to the nuclear substructure. PMID- 8359212 TI - Contact inhibition of cell spreading: a mechanism for the maintenance of thyroid cell aggregation in vitro. AB - When freshly isolated porcine thyroid cells are stimulated with thyrotropin (TSH) they organize to form functional follicles in conventional substrate-adherent culture. Cell aggregation is essential for follicular reorganization and is likely to be influenced by the balance between cell-cell adhesion (promoting aggregation) and cell-substrate adhesion (favoring spreading and monolayer formation). Recently we observed that TSH potentiated cell-cell adhesion and in the present study we have sought evidence that TSH might also regulate cell substrate adhesion. Two parameters of cell-substrate adhesion, namely, cell attachment to collagen and cell spreading upon collagen, were measured using preparations of isolated single cells and of multicellular aggregates. TSH had no effect upon the attachment or spreading of single cells, but inhibited aggregate spreading without affecting aggregate attachment. The possibility that cell-cell contact modulated the response to TSH in aggregates, but not in single cells, was confirmed using a cell-free membrane preparation which inhibited the spreading of single cells but not their rate of attachment. Moreover, TSH potentiated the inhibitory effect of membranes on the spreading of single cells. Heparin also specifically inhibited the spreading of both single cells and cell aggregates, suggesting that a heparin-sensitive adhesive mechanism might be recruited as thyroid cells spread. We conclude that thyroid cell-substrate adhesion is regulated by a synergistic interaction between cell-cell contact and TSH which preferentially inhibited cell spreading but not attachment. Such contact dependent inhibition of cell spreading is predicted to preserve cell aggregates and hence contribute to the maintenance of thyroid follicular differentiation in vitro. PMID- 8359213 TI - Most nuclear proteins are imported by a single pathway. AB - Using kinetic competition analysis, we show that the import of most Xenopus oocyte nuclear proteins is directed by a single family of nuclear localization signals (NLS). The transport of microinjected [35S]methionine-labeled nuclear proteins into oocyte nuclei was challenged with saturating concentrations of SV40 large T-antigen NLS peptide-BSA (P(Lys)-BSA) and was assessed by SDS-acrylamide gel electrophoresis and fluorography. P(Lys)-BSA was effective at competing the import of virtually all larger polypeptides but had a less marked effect on the mediated import of many smaller polypeptides. Wheat germ agglutinin, an inhibitor of nuclear pore complex function, enhanced the competitive effects of P(Lys)-BSA on the import of both large and small polypeptides. These data indicate that most 35S-labeled Xenopus oocyte nuclear proteins, including nucleoplasmin, contain NLSs that are functionally related to the T-antigen NLS and probably employ the same cytosolic NLS receptor(s). PMID- 8359214 TI - Mechanisms of flagellar excision. I. The role of intracellular acidification. AB - It has previously been shown that exposure of Chlamydomonas to low pH induces the cells to shed their flagella. In the present paper we report that a 30-s treatment with 20 mM acetic, carbonic, formic, or benzoic acid at pH 4.0 will induce flagellar excision. In contrast, 20 mM concentrations of the stronger aspartic, phosphoric, citric, and tartaric acids (pH 4) do not induce excision. Further, the excision efficacy of acetate is a function of the concentration of protonated acetate. Thus, excision correlates with the presence of a protonated, membrane-permeant species of acid. Relative to acetate, the more permeant benzoate induces excision at a much lower concentration of protonated acid. We conclude that a flux of acid into the cell is the signal for excision. Previous work has shown that detergent-permeabilized cells excise their flagella in response to calcium but not in response to low pH. This suggests that the acidification of intact cells triggers excision by stimulating an increase in intracellular calcium. We have previously reported that the source of this calcium might be IP3-sensitive. In our model for the mechanism of pH-induced flagellar excision, a flux of acid into the cell activates phospholipase C, leading to IP3 production, the activation of an IP3-gated calcium channel (located on either an intracellular or surface membrane), and an increase in cytosolic calcium, which is the trigger of flagellar excision. PMID- 8359215 TI - Phenotypic and cell cycle analysis of human peripheral blood mononuclear cells activated with interleukin-2 and/or OKT3. AB - The poor clinical response rates of cancer patients following immunotherapy with interleukin-2 (IL-2) and other cytokines has prompted attempts to enhance the response rate by using combinations of biological response modifiers. Peripheral blood mononuclear cells (PBMC) respond to interleukin-2 and mediate non-MHC restricted cytotoxicity and cell proliferation. The addition of anti-human CD3 monoclonal antibody OKT3 has been reported to increase cytotoxicity by increasing the number of cells generated in response to the two stimuli; however, our results could not confirm this finding. In the present study we have investigated the proliferative capacity of individual populations of PBMC responding to IL-2 and OKT3 compared to either stimulus alone, in order to identify possible reasons for the failure of OKT3 to generate enhanced cytotoxic responses. PBMC were stained with monoclonal antibodies to surface antigens and propidium iodide in order to determine the phenotype of populations of PBMC progressing through the cell cycle. OKT3 alone caused an increase in PBMC progressing through the cell cycle, and addition of recombinant human IL-2 (rhIL-2) sustained this response. A higher percentage of CD56- or CD16-positive cells responded to the rhIL-2 alone, but the addition of OKT3 lowered the percentage of this phenotype and increased the number of CD3-positive T cells, which additionally demonstrated an increased CD25 expression. Comparison of the phenotypes progressing through the cell cycle in response to OKT3 plus rhIL-2 or rhIL-2 alone showed that a higher percentage of all populations responded to OKT3 plus rhIL-2, compared to IL-2 alone. Using flow cytometric cell sorting, those populations of cells with cytolytic activity were identified. Using flow cytometry, it was also possible to show minority cell populations (i.e., those representing less than 5% of the total number of cells) responding to individual stimuli and entering the cell cycle. This technique therefore offers distinct advantages over conventional proliferation assays. PMID- 8359216 TI - Binding and activation of plasminogen at the surface of human keratinocytes. AB - Plasmin is thought to be involved in the pericellular proteolysis of the human epidermis under physiological and pathological conditions. Plasmin is provided by activation of the proenzyme plasminogen. We have explored in vitro whether plasminogen is bound and activated at the keratinocyte surface, a possible mechanism for providing plasmin in the pericellular space. Plasminogen and plasmin could be eluted from the surface of keratinocytes grown in serum containing medium. When plasminogen was added to cultured keratinocytes it was activated by cell-associated urokinase-type plasminogen activator. The activation required plasminogen binding to the cell surface. Plasminogen binding by keratinocytes was saturable and proceeded in a time- and concentration-dependent manner. Surface-bound plasmin was rapidly displaced from the surface into the culture supernatant. When compared to plasmin in solution surface-bound plasmin was relatively protected from interaction with the specific inhibitor alpha 2 antiplasmin. Addition of exogenous plasmin or plasmin generation by the keratinocyte-associated plasminogen activators was ensued by the detachment of adherent keratinocytes in culture. Along the same line, plasmin counteracted keratinocyte adhesion to fibrin-coated but not to collagen-coated culture plates. The findings indicate that plasmin may be generated in the pericellular space of keratinocytes and may interfere with the adhesion to particular extracellular substrates. PMID- 8359217 TI - S-100 protein in rat brown adipose tissue under different functional conditions: a morphological, immunocytochemical, and immunochemical study. AB - The brown adipose tissue (BAT) is responsible for nonshivering thermogenesis, exhibiting changes in cell morphology related to the functional conditions. In stimulated BAT (neonatal period, cold acclimation) the large majority of adipocytes become multilocular and active, while in inactive BAT (warm acclimation) most cells are pauci- or unilocular and inactive, very similar to white adipocytes. It is well known that white adipocytes are sites of concentration of S-100, a calcium-binding protein originally isolated from the nervous system and later detected also in nonneural cell types, whereas data on the possible presence of this protein in BAT are lacking. The present study used morphological, immunocytochemical, and immunochemical methods to investigate the presence of S-100 protein in BAT under different functional conditions. We found that S-100 was present in both stimulated and inactive BAT and that is was expressed in significantly higher quantities in the latter than in the former. The multilocular cells were always negative (in both active and inactive tissue), whereas the pauci- and unilocular cells were always S-100-positive under both functional conditions. These data suggest that only pauci- and unilocular brown adipocytes express S-100 protein, thus manifesting a possible relationship between S-100 and cell morphology. PMID- 8359218 TI - Induced endocytosis in human fibroblasts by electrical fields. AB - Electroporation creates transient pores through which exogenous molecules can gain access to the cell cytoplasm. However, the electrical events associated with this phenomenon may perturb membrane-dependent events such as endocytosis. To measure the effect of electroporation on endocytosis, suspensions of human gingival fibroblasts were subjected to 5-ms electrical discharges, allowed to recover for variable periods of time, incubated with fluorescent probes, and then analyzed by flow cytometry. Incubation of electroporated fibroblasts with FITC conjugated bovine serum albumin (BSA) to label moities on cell membranes nonspecifically demonstrated a time-dependent increase of internalized probe for up to 90 min after electroporation. Pretreatment incubation of cells with cytochalasin D abrogated the increased internalization of FITC-BSA due to electroporation. Compared to controls, fluorescence signals due to internalization of surface glycoproteins with FITC-concanavalin A were 43% higher after electroporation and treatment with endoglycosidase F or H to reduce probe associated with surface membrane. Confocal microscopy confirmed intracellular labeling and reduction of membrane-associated probe by the enzyme. Assessment of nonspecific FITC-Con A labeling of cells by pretreatment with alpha-methyl D mannoside showed that labeling was largely (92%) specific. Compared to controls, electroporation induced a 60% increase of internalization of lucifer yellow, a fluid-phase endocytosis marker. Dual fluorescence labeling of membrane phosopholipids by FITC and TRITC-DHPE demonstrated an increased acidification after electroporation that was time dependent, indicating that electroporation induced more rapid entry of membrane lipid into endosomal compartments. These data demonstrate that the electrical fields used in electroporation of fibroblasts cause an actin-dependent increase in the internalization of all membrane components examined and an increased rate of probe entry in to acidifying compartments. PMID- 8359219 TI - Differential patterns of expression of three C/EBP isoforms, HNF-1, and HNF-4 after partial hepatectomy in rats. AB - Regenerating liver provides a system for studying the mechanisms controlling regulated proliferation of differentiated hepatocytes. A set of transcription factors termed hepatocyte nuclear factors (HNF-1, -3, -4) and CCAAT/enhancer binding protein (C/EBP) isoforms are known to regulate several genes predominantly expressed in the liver. To assess whether these factors might be involved in the hepatocyte proliferation program, we have studied the expression of the three C/EBP isoforms C/EBP alpha, C/EBP beta, and C/EBP delta and the two hepatocyte-enriched transcription factors, HNF-1 and HNF-4, in rat liver at various time points after partial hepatectomy and sham operations using transcriptional "run-on" assays and Northern blot and Western blot experiments. We report here that partial hepatectomy in rats leads to dramatic changes in the pattern of expression of some of these genes. The three C/EBP isoforms are differentially regulated in response to partial hepatectomy and are likely to play different roles in determining the proliferation/differentiation state of hepatocytes. In particular, C/EBP alpha expression is rapidly down-regulated, whereas C/EBP delta is induced. C/EBP beta expression is also increased, although an increase is also observed after sham operation. The drastic decrease in C/EBP alpha under these conditions of active DNA synthesis and rapid cell proliferation further supports the concept of a potential incompatibility between high C/EBP alpha protein levels and cell proliferation. The patterns of transcriptional rates of HNF-1 and HNF-4 during the different stages of the regenerative process are similar. However, HNF-1 steady-state mRNA and protein levels are significantly changed while HNF-4 remains virtually unaffected, indicating that post-transcriptional mechanisms are also involved in the regulation of HNF-1 gene expression. PMID- 8359220 TI - Senescence stimulates U937-endothelial cell interactions. AB - Progressive pathophysiologic modifications of endothelial cells are associated with aging. In vitro, endothelial cell senescence is accompanied by the failure to proliferate as well as by perturbations in gene expression. Here we show that (i) senescence enhances monoblastoid U937 cell adhesion to the endothelial monolayer; (ii) the enhanced interaction between senescent endothelial cells and U937 cells is mediated, at least in part, by the overexpression of ICAM-1; and (iii) LPS and interleukin 1 alpha, but not tumor necrosis factor alpha, are unable to stimulate the adhesion of U937 to senescent endothelial cells. Since monocyte adhesion to the endothelium is an early event in atherosclerosis, the altered adhesive properties observed in senescent cells could give insights into the formation of atherosclerotic lesions. PMID- 8359221 TI - Nonisotopic ultrastructural mapping of transcription sites within the nucleolus. AB - A nonradioactive ultrastructural method based on the incorporation of 5 bromouridine-5'-triphosphate into the RNA of streptolysin O-permeabilized cultured HeLa cells is described and used for the visualization of rRNA transcription sites. Even though the method provides much better resolution than ultrastructural autoradiography, the results obtained do not allow the assignment of rRNA transcription to a single nucleolar structural component. We locate the rRNA transcription sites at the border region of fibrillar centers with dense fibrillar components. In addition, the method represents a convenient tool for the in situ immunodetection of extranucleolar RNA synthesis. PMID- 8359222 TI - Uvomorulin, LAMP-1, and laminin are substrates for cell surface beta-1,4 galactosyltransferase on F9 embryonal carcinoma cells: comparisons between wild type and mutant 5.51 att- cells. AB - Intercellular adhesions in F9 embryonal carcinoma cells are primarily dependent upon two types of cell adhesion molecules: uvomorulin (Um or E-cadherin), which facilitates intercellular adhesion by homophilic binding, and cell surface beta 1,4-galactosyltransferase (GalTase), which binds terminal N-acetylglucosamine residues on consociate glycoprotein substrates on adjacent cell surfaces. The variant F9 cell line, 5.51 att-, undergoes initial cell aggregation, but fails to form the mature intercellular adhesions characteristic of wild-type F9 cells. The 5.51 att- cells show reduced Um expression; however, previous studies have shown that reduced levels of Um are not responsible for the att- mutant phenotype. Therefore, in this study we determined whether the att- mutant phenotype was the result of altered expression of surface GalTase or of its consociate glycoprotein substrates. Surface GalTase was found to be expressed normally on 5.51 att- cells. Furthermore, the initial intercellular adhesions characteristic of reaggregating 5.51 att- cells were dependent upon surface GalTase, since anti GalTase antibodies inhibited 5.51 intercellular adhesion. Preliminary studies showed that the interaction of surface GalTase with its consociate glycoprotein substrates was abnormal on 5.51 att- cells. To define the biochemical basis for this observation, specific glycoprotein substrates for cell surface GalTase were identified and their expression and utilization were compared between wild-type and 5.51 att- cells. In wild-type cells, uvomorulin (Um), lysosome-associated membrane protein-1 (LAMP-1), and laminin (Lm) were shown to be substrates for cell surface GalTase, suggesting that they may participate in GalTase-specific adhesions. Moreover, the interaction between GalTase and these glycoproteins exhibited characteristic changes during retinoic acid-induced F9 cell differentiation. In contrast to that seen on wild-type cells, surface GalTase interaction with Um, LAMP-1, and Lm was atypical on 5.51 att- cells, resulting, in part, from increased synthesis of oligosaccharide substrates for surface GalTase, as determined by size exclusion and lectin affinity chromatography. N Acetylglucosaminyltransferase activity was elevated in 5.51 att- cells and likely responsible for the increased expression of GalTase oligosaccharide substrates. These results suggest that mutant 5.51 att- cells are able to maintain residual intercellular adhesions because of increased expression of oligosaccharide substrates for cell surface GalTase. The impact of aberrant GalTase-specific adhesions on the ability of 5.51 att- cells to form mature intercellular adhesions and to differentiate in response to retinoic acid is discussed. PMID- 8359223 TI - DNA fragmentation and cytolysis in U937 cells treated with diphtheria toxin or other inhibitors of protein synthesis. AB - We treated the human monoblastoid cell line, U937, with various cytotoxic proteins or drugs that specifically inhibit protein synthesis and monitored the cells for degradation of chromosomal DNA and other changes. In cells treated with diphtheria toxin (DT), Pseudomonas aeruginosa exotoxin A, ricin toxin, and abrin toxin the chromosomal DNA was degraded into oligonucleosome-sized fragments, the chromatin became condensed, and the cell nuclei fragmented. All of these changes are characteristic of cells undergoing apoptosis, or programmed cell death. Various drugs, including puromycin, cycloheximide, emetine, and anisomycin produced similar changes. An enzymically attenuated mutant of DT, DT-E148S, produced effects identical to those produced by the native toxin, except that a higher concentration of toxin was required, corresponding to the reduction in ADP ribosylation activity. In all cases, DNA degradation and other changes were observed only after the rate of protein synthesis was reduced to low levels, approximately 10% or less of normal levels. These results imply that inhibition of protein synthesis in U937 cells induces apoptosis, regardless of the mechanism of action of the inhibitor. Differences in the kinetics of induction of apoptosis by the various inhibitors may reflect secondary effects on other aspects of cellular physiology. PMID- 8359224 TI - Ca2+ and Zn2+ dependence of DNA synthesis in untransformed and in Ha-ras(val-12) expressing NIH 3T3 cells. AB - The role of Ca2+ and Zn2+ in the initiation of DNA synthesis in NIH 3T3 fibroblasts and c-Ha-ras(val-12) oncoprotein-expressing (NIH 3T3) cells has been studied. Entrapment of the Ca2+ chelator, BAPTA (30 microM), into the cells totally blocked a serum-induced rise in cytosolic free Ca2+ ([Ca2+]i) as determined with fura-2. Serum starvation for 24 h considerably reduced DNA synthesis in control NIH 3T3 fibroblasts. BAPTA treatment reduced serum-induced DNA synthesis and totally inhibited platelet-derived growth factor-induced DNA synthesis in these cells. DNA synthesis of the c-Ha-ras(val-12)-expressing fibroblasts was little affected by serum starvation and unaffected by entrapment of BAPTA into the cells. Intracellular Zn2+ was measured using the fluorescent probe TSQ in intact cells. As determined using image analysis the TSQ fluorescence was distributed throughout the cytoplasm and concentrated around the nucleus. The permeable Zn2+ chelator, TPEN, at a concentration of 10 microM, caused a maximal reduction in TSQ-available Zn2+. This concentration of TPEN totally blocked DNA synthesis both in control and c-Ha-ras(val-12)-expressing fibroblasts. Upon addition of 11 microM Zn2+ DNA synthesis was restored even after TPEN addition. [3H]Thymidine incorporation itself was also sensitive to TPEN treatment. The results suggest that c-Ha-ras(val-12)-induced proliferation is independent of changes in [Ca2+]i. A specific role of Zn2+ in c-Ha-ras-induced proliferation is unlikely since ras-expressing and control cells reacted similarly to Zn2+ deprivation. There seems to be a constant requirement for the presence of Zn2+ in cell proliferation. PMID- 8359225 TI - Protein kinase C-mediated inhibition of vascular smooth muscle cell proliferation: the isoforms that may mediate G1/S inhibition. AB - The role of protein kinase C (PKC) in the regulation of vascular smooth muscle cell proliferation was studied using not only phorbol ester but also diacylglycerol, with regard to the molecular species of PKC. Phorbol 12,13 dibutyrate (PDBu) and 1,2-dioctanoylglycerol (DOG) both potently inhibited serum stimulated DNA synthesis and cell population doubling. The PDBu effect on DNA synthesis was maximal when applied at late G1. Neither PDBu nor DOG inhibited DNA synthesis in cells incubated with phorbol 12-myristate 13-acetate (PMA) for 24 h, which down-regulates PKC. Moreover, long exposure to PMA shortened the G1 period and the cell population doubling time. Therefore, a PKC isoform(s) that can be activated by phorbol ester and down-regulated by long exposure to PMA should be involved in the G1/S inhibition. A PKC enzyme assay of the soluble proteins extracted from late G1 cells and fractionated by anion exchange and hydroxylapatite chromatography showed that the activity eluting with PKC-alpha predominated, whereas that eluting with PKC-zeta was detectable. The former was dependent on Ca2+ and phorbol ester but the latter was not. PKC-zeta appeared to be expressed as two subspecies of M(r) 70 and 80 kDa. In cells incubated with PMA for 24 h, the activity eluting with PKC-alpha was completely abolished, whereas the significant activity eluting with PKC-zeta (70 kDa) remained. On the other hand, a relatively low, Ca(2+)-independent activity eluted with PKC-epsilon from the particulate fraction. This was reduced by long exposure to PMA, although not completely. Therefore, PKC-alpha and -epsilon may be the most probable mediators of the G1/S inhibition. PMID- 8359226 TI - Erythropoietin as a mitogen for fetal liver stromal cells which support erythropoiesis. AB - Fetal liver stromal cells established from 13-day-old embryos support erythropoiesis in vitro in combination with erythropoietin (Epo). Epo stimulated growth of these stromal cells in a dose-dependent manner and mRNA for Epo receptor was detected. These results suggest the possible involvement of Epo in the generation of the fetal erythropoietic microenvironment during development. PMID- 8359227 TI - The close relationship between DNA replication and the selection of differentiation lineages of human erythroleukemia cell lines K562, HEL, and TF1 into either erythroid or megakaryocytic lineages. AB - The selection of differentiation lineages into either erythroid or megakaryocytic series was analyzed with human erythroleukemia cell lines K562, HEL, and cytokine dependent TF1. A tumor promoter, TPA, induced a megakaryocyte marker, glycoprotein IIb/IIIa (GP IIb/IIIa) or IIIa (GP IIIa), but suppressed erythroid differentiation. On the other hand, aphidicolin, which is a potent inhibitor of DNA replication, inhibited GP IIb/IIIa or IIIa expression, but induced the expression of erythroid phenotypes. These phenomena were observed in all erythroleukemia cell lines tested. The bromodeoxyuridine labeling experiments indicated that de novo DNA synthesis was completely suppressed by aphidicolin treatment but was well preserved in TPA-treated cells. Among these three cell lines, erythropoietin (EPO) treatment induced erythroid differentiation of TF1 cells, which was dependent on GM-CSF or IL-3. In this case, EPO functioned as the survival factor and mild stimulator for cell proliferation as well as the inducer of erythroid differentiation. However, when either GM-CSF or IL-3 was depleted from the culture medium, TF1 ceased cell growth; concomitantly, hemoglobin positive cells appeared, which is consistent with the results obtained with aphidicolin. The incubation of K562 cells for 48 h with either TPA or aphidicolin induced the irreversible commitment of cells to megakaryocytic and erythroid lineages, respectively. Our results using three different erythroleukemia cell lines suggest that a possible linkage between the DNA replication system and the selection of a differentiation lineage is the common feature of human erythroleukemia cell lines, and that these culture systems provide a suitable model for the analysis of the signal transduction system for differentiation lineage selection. PMID- 8359228 TI - Genes coding for basement membrane glycoproteins laminin, nidogen, and collagen IV are differentially expressed in the nervous system and by epithelial, endothelial, and mesenchymal cells of the mouse embryo. AB - The pattern of laminin A, B1, B2, nidogen, and collagen alpha 1 (IV) gene expression in the 12.5-day mouse embryo was determined by in situ hybridization. Laminin B1, B2, and collagen alpha 1 (IV) mRNAs were present in many epithelial and mesenchymal compartments. Laminin A mRNA had a more restricted distribution, being present in cells closely associated with basement membranes and also in the ependymal layer of the neural tube. Nidogen was not produced by any epithelium, but was abundant in mesenchymal and endothelial cells. These results demonstrate that mesenchymal cells contribute significantly to basement membrane production, and that many cells not associated with typical basement membranes produced high levels of mRNAs coding for basement membrane components. Very few cell types produced all five gene products, and some tissues preferentially expressed only one or two of the five genes. This study shows that basement membranes at the epithelial-mesenchymal interface in the majority of mouse embryonic tissues are assembled from components derived from both cell types, and that heterogeneous matrix structures containing different laminin subunits and/or nidogen are likely to be present in the central nervous system and other tissues of the midgestation mouse embryo. PMID- 8359229 TI - Parathyroid hormone-related protein production by normal human keratinocytes in vitro. AB - The role of parathyroid hormone-related protein (PTHrP) and its regulation in normal epidermal physiology is not currently known. Recent evidence suggests that PTHrP production may be related to the degree of differentiation of keratinocytes in vitro. This investigation characterized the production of PTHrP by normal human foreskin keratinocytes (NHFK) during both spontaneously occurring and induced differentiation in vitro. PTHrP production in keratinocyte serum-free conditioned medium was determined using an N-terminal radioimmunoassay for human PTHrP (1-36). Agents known to stimulate (calcium, 1,25-dihydroxyvitamin D3) or inhibit (transforming growth factor-beta) keratinocyte differentiation were examined for their ability to alter production of PTHrP. Measurements of cell number and involucrin content of the cultures were made to confirm the effects of these agents on keratinocyte growth and differentiation. The production of PTHrP in control cultures (under low calcium conditions, 0.08 mM) was decreased and involucrin content increased (P < 0.01) after the cells became confluent. The addition of 1 mM calcium to keratinocyte medium increased cell number and involucrin content of the cultures (P < 0.05) but inhibited production of PTHrP (P < 0.01). The 1,25-dihydroxyvitamin D3 (10 nM) had no significant effect on cell number or PTHrP production, but increased involucrin content (P < 0.05). Transforming growth factor-beta (5 ng/ml) decreased both cell number (P < 0.05) and involucrin content (P < 0.01), but significantly stimulated PTHrP production (P < 0.01). These data indicate that the production of PTHrP by NHFK is inhibited with the onset of both spontaneously occurring and calcium-induced differentiation in vitro, while transforming growth factor-beta inhibited differentiation and upregulated PTHrP production in normal human keratinocytes. PMID- 8359230 TI - Phenomenology. PMID- 8359231 TI - Why are some references more equal than others? PMID- 8359232 TI - Cure of osteopetrosis in op/op mice by bone grinding and good food? PMID- 8359233 TI - Posttranscriptional regulation of colony-stimulating factor-1 (CSF-1) and CSF-1 receptor gene expression during inhibition of phorbol-ester-induced monocytic differentiation by dexamethasone and cyclosporin A: potential involvement of a destabilizing protein. AB - Colony stimulating factor-1 (CSF-1) and its receptor (encoded by the c-fms proto oncogene) have long been recognized as playing an important role in monocytic differentiation. However, the regulation of expression of the CSF-1 and c-fms genes during inhibition of monocytic differentiation has not been fully characterized. The present studies demonstrate that dexamethasone (dex) and cyclosporin A (CsA) resulted in inhibition of 12-O-tetradecanoylphorbol-13 acetate (TPA)-induced monocytic differentiation of HL60 cells, as well as TPA induction of c-fms and CSF-1 transcripts. These agents also blocked TPA-induced adherence, alpha-naphthyl acetate esterase staining, and the development of a more differentiated morphology. Nuclear run-off analyses revealed no effect of either of these agents on transcription of either c-fms or CSF-1 genes in TPA treated HL60 cells. Measurements of c-fms transcript half-life confirmed post transcriptional regulation of c-fms transcript levels after the addition of dex or CsA to TPA, both of which resulted in a decrease in c-fms mRNA half-life. Others have suggested that TPA results in the stabilization of c-fms mRNA in HL60 cells through induction of a labile mRNA stabilizing protein. We observed, however, that the inhibition of protein synthesis by cycloheximide (CH) in this setting of early monocytic differentiation increased both c-fms and CSF-1 steady state transcript levels. While CH had no effect on the transcription of c-fms and CSF-1 genes in TPA/dex- or TPA/CsA-treated HL60 cells, c-fms mRNA was stabilized after the addition of CH to TPA/dex-treated cells. Taken together, our results suggest the existence of a labile mRNA regulatory protein or proteins, whose actions include destabilization of both c-fms and CSF-1 transcripts after inhibition of TPA-induced monocytic differentiation by dex or CsA. PMID- 8359234 TI - Expression of membrane-bound burst-promoting activity is mediated by allogeneic effector cells. AB - To investigate whether "self" and "non-self" recognition processes are involved in murine erythropoiesis, the expression of membrane-bound burst-promoting activity (mBPA) was determined for B lymphocytes purified from spleens of CF-1, C57 BL/6J, B6021-7115, and CAF-1J mice using syngeneic and allogeneic bone marrow cultures. Addition of B lymphocyte conditioned medium (LCM), shed membrane derived vesicles, or intact plasma membranes prepared from syngeneic murine cells stimulated erythroid burst-forming unit (BFU-E) proliferation by two- to three fold above control levels. BFU-E proliferation was increased by six- to eight fold, however, when LCM, shed membrane vesicles, or plasma membranes purified from allogenic B lymphocytes were used as sources of growth-stimulatory activity. Bioactivity was immunoprecipitated from detergent extracts of membranes purified from both allogeneic and syngeneic lymphocytes with a monoclonal antibody that specifically recognizes mBPA, suggesting that the factors expressed by these cells share antigenic determinants. The results indicate that allogeneic effector cells are a more potent source of mBPA-like molecules than are syngeneic cells, suggesting that immune mechanisms may be involved in inducing erythroid growth factor expression at the B cell surface. PMID- 8359235 TI - Modified celluloses for erythrocyte deformability fractionation. AB - Cellulose columns have been used to separate erythrocytes into deformability classes, but recoveries have been variable and incomplete. Columns of modified cellulose (propylaminocarbonylmethyl cellulose [PAC] and butylisourea cellulose [BIC]) were effective in increasing the recovery of both normal and sickle cells applied to the columns, with reasonable yields of rigid cells in the late fractions. In particular, sickle cells were recovered in 95% yield, and late eluting cells had a sharply reduced deformability index. PMID- 8359236 TI - Development and application of a sensitive radioimmunoassay for human granulocyte macrophage colony-stimulating factor able to measure normal concentrations in blood. AB - A radioimmunoassay (RIA) for human granulocyte-macrophage colony-stimulating factor (GM-CSf) was developed based on antibodies from rabbits immunized with glycosylated recombinant human (rh) GM-CSF. The antibodies are specific for human GM-CSF and do not crossreact with other human hematopoietic growth factors or mouse GM-CSF. The antibodies also react with nonglycosylated rhGM-CSF, so E. coli derived rhGM-CSF can be assayed as well. The RIA has a measuring range of about 10 to 200 pg/mL. Normal blood was found to contain 13 to 24 pg/mL (95% limits) with a mean of 18.5 pg/mL (n = 34). Monoclonal antibodies against GM-CSF could remove GM-CSF from normal human serum, thus ensuring that the GM-CSF measured in serum is real and does not represent nonspecific reactivity with our polyclonal rabbit antibodies. While previously published methods have been unable to measure GM-CSF in human serum under normal conditions, our more sensitive RIA does confirm the presence of small amounts of GM-CSF in serum or plasma and can therefore be used to detect fluctuations of GM-CSF in health and in disease. PMID- 8359237 TI - Induction by interleukin-7 of lymphokine-activated killer activity in lymphocytes from autologous and syngeneic marrow transplant recipients before and after systemic interleukin-2 therapy. AB - Therapy with recombinant lymphokines after autologous bone marrow transplantation (ABMT) is being explored as a way to prevent relapse. Lymphokine therapy may exert an antitumor effect through a variety of mechanisms, including the induction of lymphokine-activated killer (LAK) cell cytotoxicity. We tested the ability of interleukin-7 (IL-7) to induce LAK cytotoxicity in peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients early after ABMT. LAK activity was defined as lysis of Daudi by PBMC after incubation with IL 7 at 10 to 100 ng/mL or IL-2 at 1000 U/mL. PBMC from four healthy subjects were cultured with either IL-7 or IL-2. IL-7 induced LAK activity in two of the four, whereas IL-2 induced LAK activity in all four. The median percent lysis (effector to-target ratio [E:T] 40:1) with IL-7 (23%) was lower than with IL-2 (67%). PBMC were obtained from 15 patients 27 to 84 days after autologous (n = 13) or syngeneic (n = 2) bone marrow transplantation (BMT) and tested for IL-7-induced LAK activity. Eleven exhibited significant activity (10% to 77% lysis at E:T 40:1). In contrast to the results in PBMC from normal subjects, in PBMC from ABMT patients IL-7 induced LAK activity of a magnitude similar to that induced by IL 2. Studies were also performed on PBMC from eight patients who had received IL-2 after ABMT (3.0 x 10(6) U/m2/d) for 4 days by continuous intravenous (IV) infusion. In seven of the eight patients, IL-7 induced significant LAK activity, which was higher than that seen in PBMC from ABMT patients who had not received IL-2. Thus, IL-7 reproducibly induced significant LAK activity in cells obtained early after autologous or syngeneic BMT. Indeed, such LAK activity was comparable quantitatively to that induced by IL-2. Finally, IL-7 induced an even greater LAK activity in vitro in PBMC obtained after ABMT and preactivated in vivo by IL-2 therapy. The results suggest that IL-7 may have a potential immunotherapeutic role, alone or with IL-2, after ABMT. PMID- 8359238 TI - Interpretation of high-resolution current source density profiles: a simulation of sublaminar contributions to the visual evoked potential. AB - Current source density (CSD) analysis provides an index of the location, direction, and density of transmembrane currents that arise with synchronous activation of neural tissue and that generate an evoked potential profile in the extracellular medium. In neocortex and other laminated structures, a simplified, one-dimensional CSD analysis can be computed by differentiation of voltages sampled at discrete points in a linear array. One-dimensional CSD analysis is a practical and accurate method for defining both regional activity patterns and neural generators of surface-recorded evoked and event-related potentials. In computing the CSD, common practices of differentiating across spatial grids of 200 microns or more and use of spatial smoothing routines help to reduce noise, but severely limit the spatial resolution available to the analysis. High resolution CSD procedures (i.e., 3 point differentiation using a spatial grid of 100 microns or less) are more suited to identification of processes within individual cortical laminae or sublaminae, but can magnify the contributions of computational artifacts. Despite the inclusion of independent indices of cellular activity (e.g., multiunit activity), both high- and low-resolution analyses may indicate current source and sink configurations for which there is more than one plausible physiological interpretation. In the present study we examined the resolving capacity and pitfalls of common CSD procedures using simulated ensembles of current dipoles. These were positioned and oriented to model the depolarization of lamina 4C stellate cells and thalamocortical afferents in macaque striate cortex. Empirically, the surface N40 appears in association with a CSD configuration which includes current sinks within the thalamorecipient (stellate) subdivisions of lamina 4C and a large current source extending considerably below 4C. Dipole ensemble contributions to the CSD profile were computed and compared to physiological data from this region. Small asymmetries in activation of model stellate laminae were sufficient to produce substantial open field contributions. However, the best fit with empirical CSD profile was found when the simulation included contributions from thalamocortical axons, along with both open and closed field contributions from dual stellate cell sublaminae. High-resolution CSD profiles were shown to be interpretable when computational artifacts characteristic of closed and open fields were identified using a series of differentiation grids. PMID- 8359239 TI - The temporary inactivation of the red nucleus affects performance of both conditioned and unconditioned nictitating membrane responses in the rabbit. AB - These experiments are part of a series of studies examining the role of the red nucleus in the performance of the conditioned and unconditioned nictitating membrane reflexes in the rabbit. Specifically, the experiments test the hypothesis that the temporary inactivation of the red nucleus selectively affects the performance of the conditioned reflex. The experiments were designed to assess the effects of lidocaine and control saline microinjections on conditioned as well as unconditioned responses in both paired and unpaired trials. Rabbits were chronically implanted with cannulae through which small injecting tubes were passed stereotaxically to the red nucleus. The animals were conditioned using a delay paradigm in which a 1 kHz tone and an air puff applied to the cornea were used as the unconditioned and conditioned stimulus, respectively. Once conditioned, the effects of either lidocaine or saline injection were evaluated while alternating paired trials with unpaired trials in which only the air puff was applied. The principal finding of this study was that the amplitudes of both the conditioned and unconditioned responses were reduced following lidocaine injection into the red nucleus. The effect on the unconditioned response amplitude could not be ascribed to any interaction between the conditioned and unconditioned responses, since it also was present in the unpaired trials. The reduction in amplitude of the conditioned and unconditioned responses was shown to be correlated with changes in other characteristics of the same responses. The data suggest that the red nucleus contributes to the performance of both the conditioned and unconditioned nictitating membrane reflexes and consequently is not likely to be involved only in pathways responsible for mediating and/or storing the engram for the conditioned reflex. PMID- 8359240 TI - A pertussis toxin-sensitive G protein mediates inhibition by morphine of spontaneous electrical activity of oxytocin neurones in anaesthetized rats. AB - We investigated the effects of intracerebroventricular (i.c.v.) pertussis toxin upon the sensitivity of supraoptic oxytocin neurones to intravenous morphine (1 5000 micrograms/kg) in urethane-anaesthetized rats. The maximal inhibitory capacity of morphine was diminished by prior administration of pertussis toxin. Some cells were tested with both morphine and with the kappa-opioid agonist U50,488 (1-5000 micrograms/kg): U50,488-induced inhibition of firing rate was apparently unimpaired by pertussis toxin pre-treatment. The opioid inhibition of firing rate seen in the absence of and after pertussis toxin pre-treatment was naloxone-reversible. Thus a pertussis toxin-sensitive G protein may mediate the inhibitory action of morphine upon supraoptic putative oxytocin neurones or inputs to them. PMID- 8359241 TI - The effect of muscimol micro-injections into the fastigial nucleus on the optokinetic response and the vestibulo-ocular reflex in the alert monkey. AB - Eye movements of four macaque monkeys were investigated after unilateral micro injections of the GABA agonist muscimol (1 microgram in 1 microliter NaCl) into the caudal fastigial nucleus, i.e. the fastigial oculomotor region. Spontaneous eye movements in the dark and in the light were tested, as well as those evoked by vestibular stimulation in the dark (sinusoidal: 0.1-0.2 Hz, +/- 40-100 deg/s, velocity trapezoid acceleration 40 deg/s2, constant velocity 120 deg/s), optokinetic stimulation (sinusoidal: 0.1-0.2 Hz, +/- 40-100 deg/s, constant velocity 60-100 deg/s), and visual-vestibular conflict stimulation. With these stimuli, smooth pursuit mechanisms (fast build-up of optokinetic slow phase velocity), the vestibulo-ocular reflex (VOR) and the velocity storage mechanism were investigated. Muscimol injections consistently led to specific eye movement changes which were maximal 30-60 min after the injection and lasted 4-6 h. The fast initial rise of OKN slow phase velocity to the contralateral side decreased by 45% (range 24%-82%) of its pre-injection value, while it was virtually unaltered on the ipsilateral side (average decrease of 1%, range from a decrease of 20% to an increase of 32%). For conflict ramp stimulation, the suppression of vestibular nystagmus was less (decrease of 50%, range 12-82%) towards the contralateral side while it remained unchanged on the ipsilateral side. The VOR in the dark and the velocity storage mechanism were not altered. For the latter, the slow build-up of optokinetic nystagmus velocity, the optokinetic afternystagmus (OKAN) and the time constant of decay for the vestibular nystagmus were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359242 TI - Experimentally induced laminar necrosis, status verrucosus, focal cortical dysplasia reminiscent of microgyria, and porencephaly in the rat. AB - Different types of cortical malformation were produced, following focal cortical freezing, electrocoagulation, focal cortical aspiration or gentle brushing of uncovered meninges, in newborn or 1- to 3-day-old rats. Malformations included laminar necrosis of the cerebral cortex, status verrucosus, focal cortical dysplasia reminiscent of microgyria, and porencephaly. Similar procedures from postnatal day 4 onwards, at a time when a reactive astrogliosis is possible, produced cavitating infarcts and tissue scars. Cytoarchitectonic studies revealed an abnormal distribution of different types of pyramidal and non-pyramidal neurons in these malformations. These indicated three subtypes of focal cortical dysplasia, which probably depend on different pathogenic mechanisms. Autoradiographic studies with [3H] methylthymidine showed normal positioning of late-generated neuroblasts in the cerebral cortex, thus suggesting preserved migration. The present experimentally induced cortical malformations are useful models of similar cortical abnormalities in humans. PMID- 8359243 TI - Priming stimulation facilitates Hebb-type plasticity in the Schaffer collateral commissural pathways of the mouse hippocampus. AB - Hebb-type plastic changes of synaptic transmission were analyzed in the Schaffer collateral-commissural pathways (SC) of the mouse hippocampal slice. Low frequency (0.05-0.1 Hz) SC stimulation (S2) was paired with intracellular depolarization (100-200 ms; 2-3 nA) of CA1 pyramidal. Postpairing facilitation of synaptic responses in picrotoxin-free medium occurred only when S2 was "primed" with neurons the preceding shock (S1) administered through the same electrode 200 ms before S2. Priming-determined disinhibition in local circuitry is supposed to be responsible for this phenomenon. PMID- 8359244 TI - Effect of optic nerve stimulation on neurons in pericruciate cortex of cats. AB - The distribution of optic chiasm input to different types of neurons in pericruciate cortex of cats agreed with previous work using light flashes. Neuron response times served to differentiate the input pathways to pericruciate cortex, and the types of neurons they influence. Input from the optic chiasm arrived in three distinct surges: the first via the superior colliculus, the second via an unidentified pathway, and the third via the visual cortex. A fourth, diffuse surge arrived in the postcruciate cortex via some unidentified pathway. Stimulation of the contralateral side of the optic chiasm had a weaker effect than stimulation of the ipsilateral side; it evoked activity at a higher threshold, with fewer spikes per response, and at a longer latency. The difference in response latency between the two sides was largest on neurons responding to the first surge, decreasing in later surges, and being least on those neurons responding to the last surge. About 2.3% of the postcruciate and 15% of the precruciate neurons responded only to optic chiasm stimulation; they were isolated in the granular layers, and their responses could not be influenced by prior cutaneous input. It is suggested that much of the visual input to pericruciate cortex serves to modulate on-going cortical output and, thereby, the behavior of the animal. PMID- 8359245 TI - Characteristics of target-reaching in cats. I. Individual differences and intra individual constancy. AB - Trajectory formation of unrestrained forelimb target-reaching was investigated in six cats. A Selspot-like recording system was used for three-dimensional recording of the position of the wrist every 3 ms with the aid of two cameras detecting infrared light emitted from diodes taped to the wrist. These measurements allowed reconstruction of movement paths in the horizontal and sagittal planes and velocity profiles in the direction of the cartesian x, y and z co-ordinates. Horizontal movement paths were smoothly curved, segmented or almost linear. Sagittal movement paths were sigmoid. The net velocity profile was usually bell-shaped with longer deceleration than acceleration, but for some slow movements the velocity profile had a plateau. When the net velocity profile was bell-shaped, the averaged sagittal movement paths and normalized x (protraction) and z (lifting) velocity profiles were virtually superimposable for fast and slow movements: thus, movement speed was changed by parallel scaling of protraction and lifting. Comparison of movement paths and velocity profiles amongst the different cats revealed considerable differences. The x profile was unimodal in one cat and double peaked in five cats: the second component was pronounced in two cats and small in the other three. The z profile was unimodal and, except for one cat, it had later onset and summit than the first component of the x profile. In contrast to the interindividual differences, there was a high degree of intraindividual constancy over 6-12 months. It is postulated that the interindividual variability depends on chance differences established early during learning of the task and that the imprinted pattern remains, resulting in intra-individual constancy. PMID- 8359246 TI - Characteristics of target-reaching in cats. II. Reaching to targets at different locations. AB - Trajectory formation of unrestrained forelimb target-reaching was investigated in relation to the effect of a change in target location. Sagittal displacement of the target (6 cm in each direction) gave a selective change of velocity in the x direction (protraction) with an increase or decrease at larger and shorter distances, respectively. In the case of a double-peaked x velocity profile, the change was mainly with respect to the first major component. The shape of the y (sideways) and of the z (lifting) velocity profiles were both almost unchanged, but the onset of the movement in the z direction changed with the x distance. Vertical displacement (4 cm up or 5 cm down) gave increased velocity in the z direction (lifting) when the target was above the normal mid-position and decreased velocity when the target was lower. The velocity was changed with constant rate of rise, so that the rise time increased when the target was elevated and shortened when the target was lowered (pulse width control policy). The change in the z velocity was not selective. In cats with a double-peaked x velocity profile, the second component decreased when the target was elevated and increased when it was lowered. With excessive lowering of the target (14 cm down), the first x velocity component was very much reduced in amplitude so that protraction depended mainly on the second x velocity component. In the cat with a unimodal x velocity profile, a second component appeared in the x and net velocity profiles when the target was excessively lowered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359247 TI - The inhibitory effect of the ventrolateral periaqueductal grey matter on neurones in the rostral ventrolateral medulla involves a relay in the medullary raphe nuclei. AB - Experiments were carried out in urethane-anaesthetised rats to determine whether the inhibition of neurones in the rostral ventrolateral medulla (RVLM) induced by stimulation in the ventrolateral periaqueductal grey matter (PAG), is mediated via a relay in the medullary raphe nuclei. Electrical stimulation in the ventrolateral part of the PAG (20-ms trains, 7 pulses, 5-100 microA) inhibited ongoing activity of neurones in the RVLM for periods of 10-120 ms (mean 43.6 ms). The duration of the inhibition was reduced by 51.1% after microinjection of GABA (40-160 nmol in volumes of 200-400 nl, 9/12 sites), but not 165 mM NaCl (8/8 sites) in nucleus raphe magnus (NRM) and the rostral half of nucleus raphe obscurus (NRO). In a further series of experiments, activation of neuronal perikarya at 17 sites in NRM or NRO by microinjection of d,l-homocysteic acid (5 40 nmol in volumes of 50-400 nl) inhibited ongoing activity of 9 out of 14 neurones in the RVLM, the other 5 being excited. We suggest that the inhibitory effect on neurones in the RVLM, which can be evoked by stimulation in the ventrolateral PAG, is mediated indirectly by activation of an inhibitory projection to the RVLM from NRM and the rostral half of NRO. PMID- 8359248 TI - Gait-related motor patterns and hindlimb kinetics for the cat trot and gallop. AB - To assess speed- and gait-related changes in semitendinosus (ST) activity, EMG was recorded from three cats during treadmill locomotion. Selected step cycles were filmed, and hip and knee joint kinematics were synchronized with EMG records. Swing-phase kinetics for trot and gallop steps at 2.25 m/s were compared for gait-related differences. Also, swing kinetics for different gallop forms were compared. With few exceptions, ST-EMG was characterized by two bursts for each step cycle; the first preceded paw off (STpo), and the second preceded paw contact (STpc). The two-burst pattern for the walk was defined by a high amplitude STpo burst and a brief, low-amplitude STpc burst; at the slowest walk speeds, the STpc burst was occasionally absent. For the trot, the STpo burst was biphasic, with a brief pause just after paw off. With increasing walk-trot speeds, the duration of both bursts (STpo, STpc) remained relatively constant, but recruitment increased. Also, the onset latency of the STpo burst shifted, and a greater proportion of the burst was coincident with knee flexion during early swing. At the trot-gallop transition, there was an abrupt change in the two-burst pattern, and galloping was characterized by a high-amplitude STpc burst and a brief, low-amplitude STpo burst. At the fastest gallop speeds, the STpo burst was often absent, and the reduction in or elimination of the burst was associated with a unique pattern of swing phase kinetics at the knee. Knee flexion during the gallop swing was sustained by two inertial torques related to hip linear acceleration (HLA) and leg angular acceleration (LAA); correspondingly, muscle contraction was unnecessary. Conversely, knee flexion at the onset of the trot swing relied on a flexor muscle torque at the knee acting with an inertial flexor torque (LAA). Rotatory and transverse gallops at 4.0 m/s had similar swing phase kinetics and ST-EMG. Gait-related changes in ST-EMG, particularly at the trot gallop transition, are not congruent with neural models assuming that details of the ST motor pattern are produced by a spinal CPG. We suggest that motor patterns programmed by the spinal CPG are modulated by input from supraspinal centers and/or motion-related feedback from the hindlimbs to provide appropriate gait specific activation of the ST. PMID- 8359250 TI - Task-related behaviour of motor units in the human temporalis muscle. AB - Muscle activity patterns in some complex human jaw muscles appear to be task sensitive. However, it is presently uncertain how changes in motor task affect motor unit (MU) behaviour in the human temporalis muscle. In this study, activity was recorded from 40 MUs in the anterior region of the muscle. The lowest sustainable firing frequency (LSFF) was reached by slow increases and decreases in firing rate, then firing was maintained at the lowest possible rate without significant pauses. An array of consecutive interspike intervals (ISI) were sampled digitally and used to measure the LSFF for each task associated with the MU. In a controlled paradigm, MU reflex inhibition was measured during the performance of different tasks. Single electrical pulses of non-noxious intensity were delivered to the gingiva near the maxillary canine tooth. During continuous MU firing at a controlled firing frequency of 10 Hz, series of pulses were delivered with increasing delays, after preselected spikes. The MUs fired continuously during the performance of 1-4 postural and tooth-contact tasks. There were significant differences in LSFFs between tasks in those MUs associated with multiple tasks. In the reflex study, all MUs were inhibited, but the magnitude of the inhibition was highly task dependent. Thus, both LSFF and reflex inhibition of temporalis MUs appear to vary with the motor task and are sensitive to the position of the jaw and the direction and location of tooth contact along the tooth row. This behaviour most likely reflects task-related changes in output from orofacial and muscle afferents. PMID- 8359249 TI - Parallels between properties of high-threshold mechanoreceptors of the goat oral mucosa and human pain report. AB - In the following experiments, we examined parallels between properties of A-delta high-threshold mechanoreceptors (HTMs; mechanonociceptors, MN, and intense pressure receptors, IPR) innervating the goat mucosa and human mucosal pain report. As suggested in previous studies, activation thresholds of afferents which are generally considered to be mechanical nociceptors are far below mechanical pain thresholds. It was determined that classification of nociceptors by frequency thresholds, i.e., the pressure at which HTMs maintained a minimum frequency (97 g/mm2 and 117 g/mm2 for IPRs and MNs respectively) brings afferent reactivity into alignment with perceptual events. The range of reactivity of the nociceptor pool paralleled pain report from "faint-weak" (142 g/mm2) to "strong intense" (277 g/mm2). It is suggested that coding of intense mechanical pain from compressive forces is likely to arise from both individual afferents, whose reactivity spanned the range, and from recruitment of afferent populations with progressively higher thresholds. PMID- 8359252 TI - Neural activity in the caudate nucleus of monkeys during spatial sequencing. AB - Single cell activity was recorded from the monkey caudate nucleus. The animal had to execute motor and oculomotor sequences based on memorized information. In each trial, the monkey had to remember the order of illumination of three fixed spatial targets. After a delay, the animal had to press the targets in the same sequence. The "task-related" cells were activated by onset of the targets and on execution of saccades or arm movements. In a majority of cells, activation did not depend only on the retinal position of the stimuli or on the spatial parameters of gaze and arm movements, but was contingent on the particular sequence in which the targets were illuminated or the movements were performed. PMID- 8359251 TI - A perceptual analysis of viscosity. AB - The perception of viscosity was studied using the contralateral limb-matching procedure in which subjects adjusted the viscosity of a motor connected to the wrist of one (matching) arm until it was perceived to be the same as that of the motor attached to the other (reference) arm. Two servo-controlled electromagnetic linear motors with computer-controlled viscosity were used to present viscosities ranging in amplitude from 2 to 1024 N.s/m to 11 subjects. Ten different viscosities were matched by subjects, and there were ten repetitions of each stimulus amplitude. The psychophysical function relating the reference to matching viscosity was linear (99% variance accounted for), and the accuracy with which the viscosities were matched (slope of 0.88) paralleled that reported previously for force, limb position and stiffness. The Weber fraction for viscosity was 0.34, which is 50% larger than that measured for stiffness and over twice that reported for force. An analysis of the movements and forces generated to perceive the reference viscosity revealed that subjects did not vary the amplitude of the movements and typically made very small excursions of the forearm, but that both the velocity of the movements and force changed significantly as a function of the reference viscosity. These findings were interpreted as indicating that the human proprioceptive system is capable of integrating information regarding force and movement velocity so as to perceive the viscosity of a mechanical system connected to the limbs, but that its sensitivity to changes in viscosity is much less than would be predicted from its capacity to detect variations in muscle force and limb movement. PMID- 8359253 TI - In vivo tracing of pathways and spatio-temporal activity patterns in rat visual cortex using voltage sensitive dyes. AB - We monitored optical signals from cortex stained with a voltage sensitive dye to study activity evoked by intracortical electrical stimulation. The objectives were to study the spatial and temporal spread of activity from intrinsic connections near the stimulating electrode and to develop a new technique to study extrinsic projections from striate cortex to extrastriate target areas. Various measures were made of the time course of the optical signal (latency, rise time, decay time, temporal summation, facilitation versus depression, and presence or absence of a slow undershoot); in general, these measures were found to vary significantly across different response positions, different experiments, and even different runs within the same experiment. The spatial distribution of responses near the stimulating electrode in striate cortex was usually elliptical and was most often elongated along the anterior-posterior axis, with a typical size (full width at 75% max) of 1.3 mm (anterior-posterior axis) by 0.75 mm (medio-lateral axis). In some cases, complex spatio-temporal patterns were observed, in which the position of the maximum optical signal shifted with time or split into multiple peaks. In eight experiments, a response focus was found in extrastriate cortex at an expected location within the lateromedial area (LM). The response focus in LM was typically about half the size of that in striate cortex. In some experiments we observed additional focal responses in the anterolateral visual area (AL). The extrastriate responses showed a significant delay (3-10 ms) in onset and time to peak relative to the striate response. The validity of this technique for determining extrinsic projections was tested in two types of experiments. In the first, stimulation from two electrodes in striate cortex generated response foci consistent with the known topographic organization of area LM. In the second, the optically measured response focus was shown to correlate with the histologically reconstructed projection of a chemical tracer injected near the site of stimulation. We discuss the chain of neurophysiological events that occur during and after focal electrical stimulation and how they relate to the observed optical signal. We conclude that direct passive responses were a small component of our signal, that the component due to action potentials in directly stimulated neurons should have occurred in the first 1-2 ms post stimulus and is small compared to the peak signal, and that overall our signals were probably dominated by a combination of asynchronously occurring action potentials and excitatory and inhibitory synaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8359254 TI - Morphology of visual callosal neurons with different locations, contralateral targets or patterns of development. AB - In kittens, callosally projecting neurons were labeled by retrograde transport of FITC- (fluorescein isothiocyanate)- and TRITC- (tetramethylrhodamine isothiocyanate)-conjugated latex microspheres injected in two different visual areas (17, 17/18, 19, or postero-medial lateral suprasylvian; PMLS) at postnatal day 3. At postnatal day 57 more than 1200 labeled neurons in visual cortical areas were intracellularly injected with 3% lucifer yellow (LY) in perfusion fixed slices of the contralateral hemisphere. The distribution of labeled neurons was charted, and LY-filled neurons were classified on the basis of their area and layer of location, and dendritic pattern. The dendritic arbors of 120 neurons were computer reconstructed. For the basal dendrites of supragranular pyramidal neurons a statistical analysis of number of nodes, internodal and terminal segment lengths, and total dendritic length was run relative to the area of location and axonal projection. Connections were stronger between homotopic than between heterotopic areas. Overall tangential and laminar distributions depended on the area injected. Qualitative morphological differences were found among callosally projecting neurons, related to the area of location, not to that of projection. In all projections from areas 17 and 18, pyramidal and spinous stellate neurons were found in supragranular layers. In contrast, spinous stellate neurons lacked in projections from area 19, 21a, PMLS and postero lateral lateral suprasylvian (PLLS). In all areas, the infragranular neurons showed heterogeneous typology, but in PMLS no fusiform cells were found. Quantitative analysis of basal dendrites did not reveal significant differences in total dendritic length, terminal, or intermediate segment length among neurons in area 17 or 18, and this was related to whether they projected to contralateral areas 17-18 or PMLS. All injections produced exuberant labeling in area 17. No differences could be found between neurons in area 17 (with transient axons through the corpus callosum) and neurons near the 17/18 border (which maintain projections to the corpus callosum). In conclusion, morphology of callosally projecting neurons seems to relate more to intrinsic specificities in the cellular composition of each area than to the area of contralateral axonal projection or the fate of callosal axons. PMID- 8359255 TI - Binocular interaction and disparity coding in area 19 of visual cortex in normal and split-chiasm cats. AB - Binocular disparity, resulting from the projection of a three-dimensional object on the two spatially separated retinae, constitutes one of the principal cues for stereoscopic perception. The binocularity of cells in one hemisphere stems from two sources: (1) the ganglion cells in the homonymous temporal and nasal hemiretinae and (2) the contralateral hemisphere via the corpus callosum (CC). The objectives of this study were, on one hand, to determine whether disparity sensitive cells are present in a "higher order" area, namely area 19 of the visual cortex, of the cat and, on the other hand, to ascertain whether the CC contributes to the formation of these cells. As in areas 17-18, two types of disparity-sensitive neurons were found: one type, showing maximal interactive effects around zero disparity, responded with strong excitation or inhibition when the stimuli presented independently to the two eyes were in register. These neurons are presumed to signal stimuli situated about the fixation plane. The other type, also made up of two subtypes of opposed valencies, gave maximum responses at one set of disparities and inhibitory responses to the other set. These are presumed to signal stimuli situated in front of or behind the fixation plane. Unlike areas 17-18, however, disparity-sensitive cells in area 19 of the normal cat were less finely tuned and their proportion was lower. In the split chiasm animal, very few cells were sensitive to disparity. These results, when coupled with behavioral data obtained with destriate animals, indicate that (1) area 19 is probably less involved in the analysis of disparity information than area 17, (2) the disparity-sensitive neurons that are sensitive to disparity are not involved in the resolution of very fine three-dimensional spatial detail, and (3) the CC only determines a limited number of these cells in the absence of normal binocular input. PMID- 8359256 TI - Differential effects of local inactivation within motor cortex and red nucleus on performance of an elbow task in the cat. AB - This study examined changes in the performance of a single-joint, elbow task produced by reversible inactivation of local regions within the proximal forelimb representation in area 4 gamma of motor cortex (MCx) and the red nucleus (RN) of the cat. Inactivation was carried out by microinjecting lidocaine, gamma aminobutyric acid, or muscimol into sites where microstimulation evoked contraction of elbow muscles. Reaction time, amplitude, and speed (velocity or dF/dt) of position and force responses elicited during inactivation were compared to control values obtained immediately prior to inactivation. In addition, we assessed qualitatively the effects of inactivation on reaching, placing reactions, and proprioceptive responses to imposed limb displacement. In the single-joint task, injections in MCx did not increase reaction time (simple or choice) and produced modest and inconsistent reductions in response amplitude (mean -8%) and speed (mean -19%). In contrast, injections of the same amounts of inactivating agents in the forelimb representation of RN consistently increased reaction time (34.4%), and increased the reaction time coefficient of variability (32%). There were small reductions in response amplitude (-4%) and speed (-10%) which were less than those produced by MCx inactivation. During reaching, however, these same injections in MCx and RN produced a substantial loss of accuracy. For MCx, this was due, in part, to systematic hypometria: for RN, inaccuracy resulted from increased variability in paw paths. Placing reactions and corrective responses to imposed limb displacements were also depressed by the cortical and rubral injections. Our results suggest that the forelimb representation in RN plays a role in the initiation of the single-joint, elbow tracking response examined here. The RN may mediate cerebellar regulation of response timing, a function that is likely to be important for interjoint coordination. Although neurons in the forelimb representations of MCx may contribute to force generation in single-joint movements, their contribution to multijoint control appears to be more important and is examined in the subsequent report (Martin and Ghez 1993). PMID- 8359257 TI - Differential impairments in reaching and grasping produced by local inactivation within the forelimb representation of the motor cortex in the cat. AB - This study analyzed changes in the performance of a reaching task and its adaptive modification produced by reversible inactivation of three sites within the forelimb representation of the motor cortex (MCx, area 4 gamma) in five cats by microinjections of muscimol. Two sites were located in the lateral MCx, rostral (RL-MCx) and caudal (CL-MCx) to the end of the cruciate sulcus, where intracortical microstimulation (ICMS) produced contraction of the most distal muscles. The third site was located more medially, in the anterior sigmoid gyrus (RM-MCx) where ICMS primarily produced contraction of more proximal muscles. The task required the animals to reach into a horizontal target well, located in front of them at one of three possible heights, to grasp and retrieve a small piece of food. The height of the reach was primarily achieved by elbow flexion. Grasping consisted primarily of digit flexion, and food retrieval consisted of forearm supination and shoulder extension. In some blocks of trials, an obstacle was placed in the path of the limb to assess the animal's ability to adaptively adjust the kinematic characteristics of their response trajectory. In normal animals, contact with the bar on the first trial triggered a corrective response at short latency that allowed the paw to circumvent the bar. On all subsequent trials, the trajectory was adapted to prevent contact with the obstacle, with a safety margin of about 1 cm. Inactivation at all sites produced a slowing of movement, a protracted and extended forelimb posture, and increased variability of initial limb position. In addition, inactivation of RL-MCx immediately produced systematic reaching errors, consisting of hypermetric movements, as well as impaired grasping and food retrieval. The degree of hypermetria was similar for all target heights and was not associated with alterations in trajectory control. During inactivation, animals did not compensate for the hypermetria by reducing paw path elevation, suggesting a defect in kinematic planning or in adaptive control. This was confirmed by finding that trajectory adaptation to avoid bar contact was impaired during RL-MCx inactivation. The short latency corrective response, triggered by contact of the limb with the obstacle was, however, preserved. Inactivation of CL-MCx did not impair aiming, grasping, or adaptation immediately after injection. However, impairments occurred after about 1 h postinjection, and at that time mimicked the effects of RL-MCx inactivation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8359258 TI - Changes induced in the representation of auditory space in the superior colliculus by rearing ferrets with binocular eyelid suture. AB - There have been conflicting reports concerning the importance of visual experience in the development of auditory localization mechanisms. We have examined the representation of auditory space in the superior colliculus of adult ferrets that were visually deprived by binocular eyelid suture from postnatal days 25-28, prior to natural eye opening, until the time of recording. This procedure attenuated the transmission of light by a factor of a least 20-25 and blurred the image so that, as long as the eyelids were still fused, the responses of visual units in the superficial layers of the superior colliculus were labile and very poorly tuned. After the eyelids were opened, the representation of the visual field in these layers appeared to be normal. Acoustically responsive units were, as usual, almost exclusively restricted to the deeper layers of the superior colliculus. However, unlike normal animals, where responses occurring only at stimulus onset predominate, most of these units exhibited sustained or multi-peaked discharge patterns. The degree of spatial tuning of individual units recorded from the normal and deprived groups of animals was not significantly different in either azimuth or elevation. Normally orientated maps of both sound azimuth and elevation were also found in the visually deprived ferrets. However, abnormalities were present in the topography and precision of these representations and consequently in their alignment with the overlying visual map. In particular, an increase was observed in the proportion of auditory units with spatially ambiguous receptive fields, in which the maximum response occurred at two distinct locations. These results indicate that patterned visual experience is not required for establishing at least a crude map of auditory space in the superior colliculus, but suggest that it may play a role in refining this representation during development. PMID- 8359259 TI - Effects of prolonged weightlessness on horizontal and vertical optokinetic nystagmus and optokinetic after-nystagmus in humans. AB - Horizontal and vertical optokinetic nystagmus (OKN) and optokinetic after nystagmus (OKAN) provided by a partial-field, binocular optokinetic stimulator were recorded in one astronaut before, during, and after a 25-day space flight. A ground-based study was performed on six control subjects. During the flight experiment, performed on flight days 5, 18, 19, and 21, the subject either had their feet attached to the deck or was free-floating. Vertical OKN gain only slightly increased in weightlessness compared with ground data, but the center of interest (CI) during vertical OKN, evaluated by the eye position in the saggital plane at the end of the fast phases relative to the straight-ahead direction, was found to be significantly changed during long-term exposure to weightlessness. The horizontal CI showed very little change in-flight, but the gain was increased. The time constant for the astronaut was small for vertical OKAN, but there was an increase in slow-phase velocity (SPV) by the end of the flight, which returned to normal postflight. These results partly confirm the data obtained during head-tilt studies on the ground and are in accordance with the hypothesis of a gravity-dependent control of vertical gaze direction during orientation reflexes. PMID- 8359260 TI - Human gaze shifts in which head and eyes are not initially aligned. AB - Most studies of rapid orienting gaze shifts generated by combined eye and head movements have focused on an experimental condition in which gaze displacements are started with the subject's eyes in the normal straight-ahead position in the orbit. Such an experimental approach does not permit a clear identification of the input signal to the head motor system, because target offset angle is the same for both the eye and head. We have studied gaze shifts in human subjects which began with the visual axis straight ahead relative to the body (i.e., gaze or line of sight aligned with body sagittal plane) and with head offset from straight ahead at various angular positions. In our experimental conditions, the amplitude of head movement during a gaze shift was nearly equal to the angular distance between the target position and the starting head position (target-re head), even though subjects were not specifically instructed to move their heads. This observation contrasts with other published reports in the literature showing considerable variability amongst subjects in the amplitude of head rotation within a given task and between tasks. The difference may be related to the initial conditions which required subjects to align the eye and head on specific starting targets, since others have shown that requiring head alignment enhances head displacement. The amplitude of the saccadic eye movement was not determined by either the target's position relative to the starting eye or head positions. The value that best described the eye movement amplitude was the eye position in the orbit at the end of the saccade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359261 TI - Coordination between the transport and the grasp components during prehension movements. AB - In this study, the possible influence of the transport on the grasp component of prehension movements was investigated. The first phase of the transport (acceleration phase) and of the grasp (finger aperture phase) kinematics were studied under conditions of visual and non-visual object presentation (prehension experiment). In the non-visual condition, object size was estimated by haptics and object position was estimated by proprioception. Eight subjects were required to reach and grasp three objects of different size located at two distances. An additional experiment (matching experiment) was carried out to control the scaling of object size in two conditions. The results showed that in the matching experiment size estimation for large objects was similar in the two conditions, whereas small stimuli were underestimated in the haptic condition. In the prehension experiment, maximal finger aperture and velocity of finger aperture were greater in the non-visual than in the visual condition, and the difference was greater for small than for large stimuli. Moreover, in both conditions, finger opening was larger for prehension movements directed to the far than to the near objects, but only for smaller stimuli. Hand trajectory variability increased in the non-visual condition and with the distance, whereas finger opening variability was only affected by the non-visual condition. For smaller stimuli, increased finger opening with distance was positively correlated with the increase in wrist variability in the visual condition, but not in the non visual condition. Furthermore, increased finger opening between visual and non visual conditions was correlated with the increase in wrist variability, for smaller objects at the near object location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359262 TI - Role of the cerebellum in visuomotor coordination. I. Delayed eye and arm initiation in patients with mild cerebellar ataxia. AB - The initiation of coupled eye and arm movements was studied in six patients with mild cerebellar dysfunction and in six age-matched control subjects. The experimental paradigm consisted of 40 deg step-tracking elbow movements made under different feedback conditions. During tracking with the eyes only, saccadic latencies in patients were within normal limits. When patients were required to make coordinated eye and arm movements, however, eye movement onset was significantly delayed. In addition, removal of visual information about arm versus target position had a pronounced differential effect on movement latencies. When the target was extinguished for 3 s immediately following a step change in target position, both eye and arm onset times were further prolonged compared to movements made to continuously visible targets. When visual information concerning arm position was removed, onset times were reduced. Eye and arm latencies in control subjects were unaffected by changes in visual feedback. The results of this study clearly demonstrate that, in contrast to earlier reports of normal saccadic latencies associated with cerebellar dysfunction, initiation of both eye and arm movements is prolonged during coordinated visuomotor tracking thus supporting a coordinative role for the cerebellum during oculo-manual tracking tasks. PMID- 8359263 TI - On the origin of the postexcitatory inhibition seen after transcranial magnetic brain stimulation in awake human subjects. AB - Non-invasive transcranial magnetic stimulation (TMS) of motor cortex induces motor evoked potentials in contralateral muscles which are thought to be conducted by the corticospinal tract. Furthermore, inhibitory actions can be elicited by TMS which appear directly after the motor evoked potential (postexcitatory inhibition, PI) and can be visualized by blockade of tonic voluntary EMG activity. It was the aim of the present study to answer the questions of whether this inhibitory action is mainly of cortical or of spinal origin, which brain area generates this inhibition, and whether the duration of PI differs between proximal and distal muscles. Experiments were performed on a total of 34 healthy volunteers. Brain stimuli were delivered with a Novametrix Magstim 200HP with a maximum output of 2.0 T, and stimulation was performed during tonic voluntary activation of the muscle under study. Stimulation strength was 1.5 times threshold level. Duration of PI was defined as the time from the onset of the motor evoked potential to the reoccurrence of the EMG background activity. PI was found more pronounced in distal hand muscles than in proximal arm and leg muscles. The largest PI values were observed when the primary motor cortex was stimulated. To test the excitability of the spinal motoneurones during PI, cortical double stimulation at various intervals was performed and the soleus H-reflex was evoked at different intervals after cortical stimulation. Neither test revealed a decrease in the excitability of the spinal motoneurones during PI. These findings imply that spinal segmental inhibitory action cannot account for PI and that, most probably, inhibitory actions within the motor cortex play a major role in the genesis of PI. PMID- 8359264 TI - Principles for learning single-joint movements. I. Enhanced performance by practice. AB - This study investigated changes in myoelectric and mechanical variables for movements made "as fast as possible" as a function of practice in the context of the dual-strategy hypothesis of motor control (Gottlieb et al. 1989b). Five male subjects made 1400 rapid elbow flexion movements in ten blocks of 20 trials over seven experimental sessions. Improved performance was defined as increased peak movement velocity, decreased peak velocity variability, increased acceleration and deceleration, a proportionately greater increase in peak deceleration than peak acceleration, and greater consistency in terminal location. The changes observed over experimental sessions were very similar to (but larger and more consistent than) those seen for the first experimental session, with the partial exception of the timing of the antagonist electromyogram (EMG). In general, the increases in the values of the measured mechanical variables covary with myoelectric measures in the same way as when subjects are asked to intentionally change speed in accordance with the rules of the speed-sensitive strategy (Corcos et al. 1989). However, there are differences between subjects in the extent to which speed changes can be attributable to the agonist muscle, the antagonist muscle, or in the timing between the muscles. In one of the five subjects, the latency of the antagonist EMG decreased over blocks on the 1st day but increased over experimental sessions and was consequently activated proportionately later in the movement. This suggests that extended practice can give at least some subjects flexibility in modifying the motor programs that underlie movement. PMID- 8359266 TI - Compensation for mechanically unstable loading in voluntary wrist movement. AB - In order to study the roles of muscle mechanics and reflex feedback in stabilizing movement, experiments were conducted in which healthy human subjects performed targeted wrist movements under conditions where the damping of the wrist was reduced with a load having the property of negative viscosity. If the movement speed and negative viscosity. If the movement speed and negative viscosity were sufficiently high, the wrist oscillated for several hundred milliseconds about the final target position. Subjects increased the activation of both wrist flexor and extensor muscles to increase joint stiffness to damp the oscillations. With practice, both the tendency to oscillate and the level of muscle activation were reduced. A small bias torque in either direction, added to the negative viscosity, enhanced the oscillations as well as the amount of flexor and extensor muscle activation during the stabilization phase of fast movements. The tendency for the wrist to oscillate was also seen during slow movements where the oscillations were superimposed upon the voluntary movement. We suggest that this reduction in mechanical stability is primarily of reflex origin. As wrist stiffness increases, the natural frequency of the wrist also increases, which in turn produces an increase in the phase lag of the torque generated by the myotatic reflex with respect to wrist angular velocity, effectively reducing damping. The oscillation frequency was often close to a critical frequency for stability at which torque, due to the myotatic reflex, lagged angular velocity by 180 degrees (6-7.5 Hz). Nevertheless, subjects were able to damp these oscillations, probably because the torque due to intrinsic muscle stiffness (in phase with position and hence lagging velocity by only 90 degrees) dominated the torque contribution of the myotatic reflex. Increasing stiffness with declining oscillation amplitude may also have contributed significantly to damping. PMID- 8359265 TI - Principles for learning single-joint movements. II. Generalizing a learned behavior. AB - The previous paper in this series showed that changes both within and between experimental sessions can be understood in the framework of the dual-strategy hypothesis of motor control, with a modification sometimes required for the timing of the antagonist muscle. The present paper extends these findings by determining how practicing movements at one distance generalizes to changes in performance at other distances. Five subjects made elbow flexion movements over five different distances (pretest). They then performed 1400 movements (seven sessions of ten blocks of 20 trials) at only one of those distances. The subjects then repeated the flexion movements over the five different distances (posttest). On the posttest, subjects decreased their average movement time by 20 ms. In addition, their movements became less variable. The electromyographic pattern of the faster movements was characterized by a more rapidly rising electromyogram, for three of the subjects, and an antagonist latency that decreased. PMID- 8359267 TI - Effects of cortical stimulation on reciprocal inhibition in humans. AB - We attempted to demonstrate convergence onto human spinal Ia inhibitory interneurons from Ia afferents and from fast conducting corticospinal axons. Stimulation of the common peroneal nerve at or below the threshold of the alpha motoneuron axons resulted in inhibition of the soleus H-reflex, attributed to reciprocal inhibition. Magnetic stimulation over the contralateral motor cortex resulted in complex modulations of the soleus H-reflex, including a short latency inhibition. To test for convergence, the two stimuli were given together so that the two inhibitions coincided. When each stimulus alone produced clear inhibition, the inhibition produced by both stimuli was less than expected, implying an interaction between the two volleys, for example, occlusion occurring in interneurons or motoneurons. When the H-reflex was relatively unaffected by one or other conditioning volley, the inhibition produced by the combined stimulation was greater than expected, as might be expected with convergence onto a common pool of interneurons. PMID- 8359268 TI - Introduction. Melatonin and the light-dark zeitgeber in vertebrates, invertebrates and unicellular organisms. PMID- 8359269 TI - Presence in and effects of pineal indoleamines at very low level of phylogeny. AB - The unicellular organism Tetrahymena contains serotonin and is able to take up the hormone from its milieu. The serotonin content of the cell changes as a function of the presence of foreign exogenous hormones. This indicates a possible role of serotonin as a chemical mediator. Exogenous serotonin stimulates the RNA synthesis of Tetrahymena, and it was the only one among the hormones studied which kept the RNA level durably high. Serotonin stimulates phagocytosis and growth of Tetrahymena, and its precursors also stimulate growth. Serotonin can imprint Tetrahymena, and as a consequence of this the effect of the hormone increases in the case of further encounters. Treatment with serotonin-related molecules soon after imprinting can reduce the effect of imprinting. Melatonin can contract the pigment cells of Planaria; however, its precursors serotonin and tryptamine can do this more intensely. Both melatonin and serotonin can influence the regeneration of Planaria, with effects which differ when different phenomena are studied. Evolutionary theories are discussed. PMID- 8359271 TI - Structures and molecules involved in generation and regulation of biological rhythms in vertebrates and invertebrates. AB - Melatonin from the retina and the pineal gland functions in neuroendocrine hierarchies. Photoreceptors--eyes and extraretinal--detect light. Oscillators- pineal and suprachiasmatic nuclei--act as pacemakers. Driven neuroendocrine rhythms carry temporal hormone signals throughout the body. Light controls melatonin: light sets the phase of the melatonin rhythm and determines the duration of melatonin synthesis. By these means, circadian rhythms (e.g., in locomotor activity and body temperature) and seasonal rhythms (e.g., in reproduction) are controlled. PMID- 8359270 TI - Calmodulin mediates melatonin cytoskeletal effects. AB - In this article, we review the data concerning melatonin interactions with calmodulin. The kinetics of melatonin-calmodulin binding suggest that the hormone modulates cell activity through intracellular binding to the protein at physiological concentration ranges. Melatonin interaction with calmodulin may allow the hormone to modulate rhythmically many cellular functions. Melatonin's effect on tubulin polymerization, and cytoskeletal changes in MDCK and N1E-115 cells cultured with melatonin, suggest that at low concentrations (10(-9) M) cytoskeletal effects are mediated by its antagonism to Ca2+-calmodulin. At higher concentrations (10(-5)M) non-specific binding of melatonin to tubulin occurs thus overcoming the specific melatonin antagonism to Ca2+-calmodulin. Since the structures of melatonin and calmodulin are phylogenetically well preserved, calmodulin-melatonin interaction probably represents a major mechanism for regulation and synchronization of cell physiology. PMID- 8359272 TI - The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates. AB - While the production of melatonin in higher vertebrates occurs in other organs and tissues besides the pineal, the contribution of extrapineal sites of melatonin synthesis such as the retina, the Harderian glands and the gut to circulating melatonin levels is still a matter of debate. The amount of melatonin found in the gastrointestinal tract is much higher than in any other organ including the pineal and the gut appears to make a significant contribution to circulating melatonin at least under certain conditions. The gut has been identified to be the major source of the elevated plasma concentrations of melatonin seen after tryptophan administration and of the changes of circulating melatonin level induced by the feeding regimen. Whereas the circadian and circannual fluctuations of the concentration of melatonin in the blood seem to be triggered by changes of the photoenvironment and its effect of pineal melatonin formation, basal daytime melatonin levels and the extent of their elevation at nighttime appear to be additionally controlled by nutritional factors, such as the amount and the composition of ingested food and therefore availability of tryptophan as a rate-limiting precursor of melatonin formation by the enterochromaffin cells of the gastrointestinal tract. PMID- 8359274 TI - Melatonin decreases the amplitude of the b-wave of the human electroretinogram. AB - In a double-blind placebo crossover study of 13 healthy volunteers, the pineal hormone melatonin (10 mg) was given at 4 pm, and the electroretinogram measured under conditions of dark and light adaptation. A significant diminution of b-wave amplitude was found under both photopic (delta = 5.4 microV, p < 0.05) and scotopic conditions (delta = 7.4 microV, p < 0.01). These data indicate that melatonin may transduce the dark signal at the level of the retina as well as the pineal. Acute administration of melatonin decreases sensitivity to light. PMID- 8359275 TI - Partition coefficients of drugs in bilayer lipid membranes. AB - The oil/water partition coefficient of drugs is widely accepted as a key parameter in drug design. The coefficients are usually determined using a bulk octanol phase to represent the lipid. The physiologically and pharmacologically relevant structure is, of course, the bilayer lipid membrane, but until now there has been no convenient means of measuring the partition coefficients of small molecules into a single bilayer. This paper demonstrates that the partition coefficient may be calculated from the change in membrane refractive index which occurs when a drug molecule partitions into the membrane. The refractive index is determined by an integrated-optics technique ideally suited to an ultra-thin structure such as a lipid bilayer. PMID- 8359273 TI - Clinical aspects of the melatonin action: impact of development, aging, and puberty, involvement of melatonin in psychiatric disease and importance of neuroimmunoendocrine interactions. AB - During the last decade we have learned much on physiological changes in the secretion of the pineal hormone melatonin (MLT) in man. Reportedly, there is little or no MLT secreted before age 3 months. Then MLT production commences, becomes circadian, and reaches highest nocturnal levels at the age of 1-3 years. During all of childhood nocturnal peak levels drop progressively by 80% until adult levels are reached. This alteration appears to be the consequence of increasing body size in face of constant MLT production during childhood. The biological significance of this MLT alteration is presently unknown. Because of conceptual considerations, major depressive syndrome (MDS) and seasonal affective disorder (SAD) have been in the focus of pineal research for several years. Although in these disorders alterations in MLT levels could not be substantiated, light therapy, a consequence of this research, was discovered as an effective treatment for SAD and perhaps for MDS. In addition, there is some recent evidence for low MLT levels in schizophrenia. Finally, the potential effect of MLT in neuroimmunoendocrine interactions is presently explored. Reportedly, in vitro studies and animal experiments give evidence for a modulatory role of MLT in the immune response. However, the exact way of this possible action of MLT remains to be clarified. Clinical studies are too scant for a meaningful estimation of MLT's involvement in human neuroimmunoendocrine interactions. PMID- 8359276 TI - Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis. AB - Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that they may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D. PMID- 8359277 TI - Protein aggregation as primary and characteristic cell reaction to various stresses. AB - Ehrlich carcinoma and EL-4 thymoma ascites cells were subjected in vitro to heat shock, ATP depletion, oxidative stress, Ca2+ overloading and iodoacetamide treatment. After the transient stresses, Triton (X-100)insoluble (TIS) fractions were isolated from the cells and analysed by electrophoresis and immunoblotting. All stresses used caused rapid aggregation of cell proteins. This was manifested in a significant rise in protein content in the TIS fractions. The protein increase was mostly due to an increase in the insolubility of actin, 57 kDa protein of intermediate filaments, 70 kDa heat shock protein (HSP 70), and some specific proteins whose insolubilization was a characteristic sign for each type of cell injury. Different survival rates in the cell lines after either stress correlated well with differences in their TIS protein accretion. Possible mechanisms for stress-induced protein aggregation and its relationship with cell viability are suggested. PMID- 8359278 TI - The width of excision of cutaneous melanoma. PMID- 8359279 TI - Mucosal malignant melanoma of head and neck: forty-eight cases treated at Istituto Nazionale Tumori of Milan. AB - A series of 48 cases of malignant mucosal melanomas treated at the Milan Cancer Institute from 1975 to 1990 is retrospectively reviewed. There were 34 males and 14 females, and their ages ranged from 21 to 79 years (mean, 58). The site of origin of the tumor was the nasal cavity in 26 cases, the oral cavity in 15, larynx in two, lip mucosa in two, pharynx in two and upper esophagus in one. At presentation, the neoplasm was limited to the primary site in 60.4% of the patients. Most patients (34) were treated with surgery alone. Nine were treated with surgery combined with chemo- and/or radiotherapy and five with radiotherapy combined with chemotherapy and/or immunotherapy. Only when surgery was part of the treatment (42 of 48 cases) the patients were rendered disease free, but no further relapse of disease was documented in only five of these patients. The observed 2- and 5-year survival rate of the entire group was 45% and 21%, respectively. The 4-year disease-free survival rate was 7%. The median interval between therapy and the first relapse was 8.5 months (range, 1-66). In 44% of the patients the first recurrence of the tumor was at the primary site. PMID- 8359280 TI - Mandible reconstruction with metallic endoprosthesis following Commando's operation for advanced head and neck cancer. Personal experience. AB - Invasion of the mandible is found in 22% to 29% of advanced (Stage III-IV) head and neck cancers; only an aggressive surgical technique, such as Commando's operation with subsequent reconstruction of tissue defects, can give a chance of cure to these patients. The reconstruction is feasible both by means of microsurgical free-tissue transfers or with alloplastic materials and myocutaneous flaps. Between 1982 and 1991, 34 patients in Stage III (n = 6; 17.7%) and IV (n = 28; 82.3%) head and neck cancers underwent Commando's operation with different types of reconstruction in 30 patients: pectoralis myocutaneous flap (n = 9), osteo-myocutaneous flap with the underlying segment of the fifth rib (n = 2), myocutaneous flap plus prosthesis (n = 17), or prosthesis alone (n = 2). Two different prostheses were implanted: the linear A-O mandibular reconstruction plate (n = 13), and the Dumbach titanium cage (n = 6). In the group of patients in which the linear A-O mandibular reconstruction plate was used there were four cases of prosthesis dislodgement and major exposure and one case of prosthesis breakage while in patients who were given the Dumbach titanium cage there were four cases of major exposure. Prosthesis removal was required in five and two patients with linear A-O and Dumbach titanium cage prosthesis, respectively. Median survival was 14 months with 28% five-year survival. In our experience, metallic prostheses with a shape and arrangement that allow a distribution of traction forces on a wider surface, with screws drilled in nonaligned points of the mandible, seem to be more reliable as they reduce the risk of dislodgement and breakage. PMID- 8359281 TI - Modified use of gate flap for the reconstruction of the lower lip. AB - Surgical excision of advanced lower lip carcinomas with adequate safety margins, in some cases, causes defects as large as three-fourths of the width of the lip or total lip defects. This paper describes a modification of nasolabial 'gate flap' for reconstruction of extensive defects of the lower lip. Splitting the flap into skin and mucosal flaps provides the surgeon more skin on the inferior aspect of the reconstruction where he needs skin without any mucosa and more mucosa on the superior aspect of the reconstruction where he needs mucosa for reconstruction of the vermilion and lower labial sulcus. Four patients with total lower lip defects have been treated with this technique. The results were quite satisfactory both functionally and cosmetically. PMID- 8359282 TI - Surgical intervention for complications caused by late radiation damage of the small bowel: a retrospective analysis. AB - We studied the records of 46 patients who had been operated on between 1974 and 1990 in The Netherlands Cancer Institute because of complications due to late radiation damage of the small bowel. Data were collected on preoperative history, surgical intervention, postoperative complications and survival. By means of Cox's proportional hazards regression analysis we sought to identify factors that contribute to complication-risk and survival. The following factors led to an increase in complication-risk: hypoalbuminemia, more than one laparotomy prior to irradiation and a short interval (< 12 months) between irradiation and surgical intervention. The following factors related to a poorer survival: incomplete resection of the primary tumor and a short interval (< 12 months) between irradiation and surgical intervention. The type of surgical intervention did not have cumulative prognostic value in relation to complication-risk or survival. As patients undergoing resections differed considerably from patients undergoing bypass-procedures, no conclusions could be drawn about the superiority of one technique over the other. We think that both types of intervention have their own field of indication. PMID- 8359283 TI - Early vulval cancer: the place of conservative management. AB - There is a trend towards conservative surgery for early vulval cancer, which is increasingly being diagnosed in younger women. In this series there were 21 patients who had lesions which had invaded to a depth of 3 mm or less. Nine patients were treated by wide local excision without any form of lymphadenectomy, and eight patients had wide local excision with ipsilateral groin dissection. In the remaining four patients, radical surgery was carried out, consisting of radical vulvectomy and bilateral lymphadenectomy. None of the 12 patients who had some form of lymphadenectomy was shown to have nodal involvement. None of the patients suffered from local recurrence or recurrence in the groin nodes. No patient died from vulval cancer, and all but one of the patients are still alive with a mean follow-up period of 54.8 months. Though there is as yet no universal agreement on the criteria for early vulval cancer, with superficial invasion there is a place for individualized treatment, when patients will benefit from less than radical surgery. PMID- 8359284 TI - Oestrogen and progesterone receptor estimation by enzyme-immunoassay on tissues removed before and after a modified radical mastectomy. AB - To investigate the possibility of receptor degradation due to devascularization of the tumour during mastectomy, oestrogen and progesterone receptors (ER and PgR) were measured by an enzyme-immunoassay (EIA) in 59 cases of primary breast cancer on samples taken before and after performing a modified radical mastectomy. Pre- and post-mastectomy samples from the same patient were analysed simultaneously in the same assay run. There was 86.4% and 93.2% agreement respectively in ER and PgR status between samples removed before and after surgery. When actual values were analysed, the post-mastectomy values were higher or lower than pre-mastectomy values with similar frequency. These random variations could be attributed to heterogeneous distribution of receptors within a tumour. The overall correlation between pre- and post-mastectomy values was excellent (ER: r = 0.810, P < 0.001; PgR: r = 0.706, P < 0.001). Devascularization of the tumour during surgery does not seem to affect the integrity of the epitopes recognized by monoclonal antibodies against ER and PgR to any significant extent. PMID- 8359285 TI - Is immediate postmastectomy reconstruction safe in the long-term? AB - A prospective case-control study of 81 patients has been carried out over 10 years comparing mastectomy with immediate reconstruction to mastectomy alone. The patients were matched for age (within 5 years), TNM stage, pathologic nodal status and operative procedure. After complete 10-year follow-up we have failed to demonstrate any long term difference in tumour behaviour. We conclude that immediate reconstruction is widely applicable and technically feasible without any long term effect on the development of local recurrence or metastatic disease. PMID- 8359286 TI - Right ventricular metastasis from choriocarcinoma: report of a rare case and review of the literature. AB - A previously healthy gravida developed chest pain and progressive dyspnea several months after delivery. A right ventricular mass rising from the septum and floating through the pulmonary valve was detected, with multiple lung nodules. With the suspicion of a primary sarcoma of the heart, she was referred for cardiac surgery. Microscopic observation of the cardiac neoplasm revealed malignant trophoblast. There was no evidence of disease in the uterus and adnexa. Combination chemotherapy with EMA-CO schedule was instituted because of the high risk score. A complete recovery was achieved after 20 weeks of treatment and the patient is free of disease 4 years after the end of chemotherapy and is now pregnant again. PMID- 8359287 TI - Inflammatory pseudotumour of the liver. AB - Inflammatory pseudotumours of the liver are uncommon, usually mistaken for malignant lesions and resected. This report describes the presentation of an inflammatory pseudotumour of the liver in a 28-year-old male which was demonstrated on C.T. scanning and diagnosed by percutaneous needle biopsy. This case was treated conservatively and spontaneously resolved within four months, emphasising the need to consider this lesion in the differential diagnosis of an intrahepatic mass. PMID- 8359288 TI - TNM system. PMID- 8359289 TI - Surgery for carotid stenosis: the quest for the ideal technique. PMID- 8359291 TI - Defective cerebrovascular autoregulation after carotid endarterectomy. AB - Correction of high grade carotid artery stenosis may result in cerebral hyperperfusion because of defective vascular autoregulation. Thus, transcranial Doppler was used to determine mean arterial flow velocity (Vmean) of the middle cerebral artery in 95 patients before and after carotid endarterectomy. Attention was focused on postoperative episodes of ipsilateral headache and hypertension. Symptoms of cerebral hyperperfusion lasted for 3 (1.5-5) h (median and range) in nine patients, and for 12 (8-14) days in nine other patients. Of these later patients, two developed seizures on the 5th and 6th postoperative day, respectively. The mean pressure difference across the stenosis was 31 (0-63) mmHg in the symptomatic group (n = 18) as opposed to only 10 (0-60) mmHg in the asymptomatic group (n = 77) (p < 0.01). In the 18 patients with headache after surgery, ipsilateral Vmean increased to 177 (130-332)% of the preoperative value (p < 0.0001), while the contralateral Vmean remained unchanged. After blood pressure was reduced in symptomatic patients with labetalol, ipsilateral Vmean decreased from 92 (69-124) to 56 (32-93) cm s-1 (p < 0.0001) as systemic arterial pressure decreased from 101 (80-128) to 88 (60-103) mmHg, with no change in contralateral Vmean. Normalisation of Vmean via reduction of arterial pressure ended episodes of headache and seizure in symptomatic patients. Thus, in patients who developed post-endarterectomy hyperperfusion, these findings clearly demonstrated that ipsilateral middle cerebral artery mean flow velocity was pressure dependent. This substantiates the hypothesis of defective autoregulation in the ipsilateral hemisphere after carotid endarterectomy, and in turn demonstrates an immediate cessation of symptoms with reduction of arterial pressure even in normotensive patients. PMID- 8359290 TI - Anticoagulants, antiaggregants or nothing following carotid endarterectomy? AB - Carotid endarterectomy (TEA) has proven to be beneficial for symptomatic patients. Anticoagulation (AC) and antiplatelet therapy (ASA) have been shown to prolong life following vascular surgery in patients with occlusive arterial disease (PAOD). To determine whether ASA or AC prolong life after TEA, retrospective analysis was undertaken, since cerebral haemorrhage is associated with the use of both drugs, especially AC. Between 1979-1986, 328 patients with stenotic lesions of the carotid bifurcation were operated upon electively. Patient survival and causes of death were the primary end points of the analysis. Recent data were obtained from the Austrian Central Bureau of Statistics. Cumulative survival rates were calculated by Kaplan-Meier estimation and differences determined by Breslow and Mantel tests. 36 patients were on AC, 157 on ASA and 135 remained without medication (0-group). Since the common risk factors in PAOD were unevenly distributed between groups, a stepwise Cox regression model was applied which revealed age (p < 0.01), cardiac pathology (p < 0.01) and diabetes (p < 0.05) as relevant for survival. Therefore, ASA patients and 0-group patients were selected and matched, employing the aforementioned prognostic criteria, and compared to the patients on long-term AC for various indications (vein bypass surgery, myocardial infarction, pulmonary embolism; i.e. data-matching). The median postoperative survival was 7.72 years for ASA and 8.48 years for AC, compared to 6.07 years for the 0-group (p = 0.0095 Breslow, p = 0.477 Mantel). There was no significant difference between AC and ASA treated patients. Irrespective of medication, the causes of death were well balanced, and no higher incidence of intracerebral haemorrhage was detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359292 TI - Can recurrent stenosis after carotid endarterectomy be prevented by low-dose acetylsalicylic acid? A double-blind, randomised and placebo-controlled study. AB - Recurrent stenosis (> 50%) after carotid endarterectomy is reported with a frequency ranging from 7-20%. 232 patients undergoing carotid endarterectomy were randomised to low-dose acetylsalicylic acid (ASA, 75 mg daily) or placebo (identical tablets). The treatment was started the day before surgery and continued for 6 months. All patients were followed clinically for 1 year. Doppler examination was performed preoperatively (n = 230) and postoperatively (n = 228) and at follow-up at 2 (n = 220) and at 6 months (n = 174) after surgery. The degree of stenosis was estimated from the maximum Doppler frequency shift in the internal carotid artery. Recurrent stenosis of 30% or more was detected in 85 of the 220 patients (38.6%) at 2 months, and at 6 months in 73 of the 174 examined patients (42.0%). Stenosis > 50% was seen in 16 patients (9.2%) and occlusion was found in four patients (1.8%) at 6 months. No difference between the low-dose ASA treated group (n = 112) compared to the placebo group (n = 108) was seen regarding recurrent stenosis. Women had an increased risk of recurrent stenosis (p < 0.001), whereas other factors such as age, hyperlipidaemia, diabetes and smoking were not associated with increased risk. Importantly, the number of neurological events did not differ between those with or without restenosis. Therefore, the indications for surgery of asymptomatic recurrent stenosis are questionable. The progress of arteriosclerosis in the contralateral carotid artery did not differ between the treatment groups. PMID- 8359293 TI - Chronic obstructive pulmonary disease and abdominal aortic aneurysms. AB - In a prospective study during the period January-May 1992, 362 consecutive out patients above 65 years of age, attending the pulmonary department for chronic obstructive airways disease (COPD), were ultrasonographically screened for an aneurysm of the abdominal aorta (AAA). Data from pulmonary function tests together with history of cardiac disease, diabetes mellitus, hypertension, hypercholesterolaemia, peripheral arterial obstructive disease, smoking and corticosteroid medication were collected. 30/282 men and 6/80 women with COPD had an AAA > or = 30 mm in diameter, which equals a prevalence of 9.9% (95% confidence limits: 6.8-13.0%). COPD patients with severe emphysema, having a decreased forced expiratory volume/vital capacity ratio (FEV/VC) of < 55%, have a significantly higher prevalence of aortic dilatation or AAA compared to COPD patients with mild or moderate decreased FEV/VC (chi-squared test: p < 0.05, alpha = 0.05). In the group of patients with AAA, significantly more smokers were seen compared to the group with normal and dilated aortas (chi-squared test: p < 0.05). PMID- 8359294 TI - Hyperhomocysteinemia in patients operated for lower extremity ischaemia below the age of 50--effect of smoking and extent of disease. AB - Moderate hyperhomocysteinemia may be a risk factor for atherosclerotic peripheral vascular disease (PVD). In order to develop PVD at an early age risk factors are more strongly expressed and hyperhomocysteinemia may be one such factor. Homocysteine is derived from methionine and is metabolised by cystathionine synthase to cystathionine or remethylated to methionine. Cystathionine-synthase activity is dependent on vitamin B6 while the remethylation of homocysteine is dependent on vitamin B12 and folate. The present study analyses homocysteine in patients operated on for lower extremity ischaemia before the age of 50. Homocysteine before and after loading with methionine, vitamin B6, B12 and folate were measured at follow-up. The patients were compared to age- and sex-matched controls. Significantly more patients than controls had hyperhomocysteinemia, 16/58 vs. 4/65, defined as fasting total homocysteine above 18.6 mumol/l. Loading with methionine did not further discriminate between patients and controls. Smoking patients had higher levels of homocysteine than non-smoking patients or smoking and non-smoking controls. Smoking patients also had lower levels of vitamin B6. When comparing patients with suprainguinal, infrainguinal and multilevel disease the highest homocysteine levels were seen in the latter group. Also, in this group smoking patients had higher homocysteine levels. Multivariate analysis revealed that homocysteine was associated with low levels of vitamin B12, folate and smoking. Smoking therefore seems to be connected to increased homocysteine levels in patients with early development of atherosclerosis, partly explained by decreased levels of B6, B12 and folate. PMID- 8359295 TI - The Gloucestershire Aneurysm Screening Programme: the first 2 years' experience. AB - 5337 men aged 65 were invited for ultrasound examination of the abdominal aorta between September 1990 and October 1992 as part of a General Practice based aneurysm screening programme covering the County of Gloucestershire. 4232 (79%) attended. 3877 (91.6%) had aortic diameters equal to or less than 2.5 cm. 302 (7.1%) had aortic diameters in the range 2.6-3.9 cm and 53 (1.3%) had a diameter of 4.0 cm or greater. Mean aortic diameter was 2.04 cm (S.D. 0.50 cm). The practicalities, costs and benefits of a community based aneurysm screening programme are discussed. PMID- 8359296 TI - Patency and morphology of fibrous polyurethane vascular prostheses implanted in the femoral artery of dogs after seeding with subcultivated endothelial cells. AB - A cell culture line was established from enzymatically-derived canine jugular endothelial cells and further cultured. Whenever sufficient cells were present, fibrous polyurethane vascular prostheses, impregnated with gelatin and coated with fibronectin, were seeded with 4.8 x 10(5)/cm2 cells, sufficient to establish a confluent monolayer, and implanted in the femoral arteries of 16 dogs. A non seeded prosthesis on the contralateral side served as control. Eight dogs received antiplatelet aggregation medication: 250 mg aspirin together with 25 mg dipyridamole, orally three times daily, starting 2 weeks prior to the implantation operation and continued for the duration of the experiment. Results show that in the non-medicated dogs all control prostheses become occluded within 3 weeks after implantation, whereas five out of eight seeded prostheses remained patent. In the medicated group, two out of eight control prostheses occluded and all seeded prostheses remained patent. Scanning and light microscopy revealed that seeded prostheses were completely lined with endothelial cells (Factor VIII positive stain) week 3 (n = 3) and 12 (n = 3) after implantation, while endothelialisation in control prostheses had advanced only 5 mm into the prostheses in 12 weeks. Two dogs of each group were included in long-term patency studies. We conclude that prostheses seeded with a confluent monolayer of endothelial cells result in superior patency rates for both medicated and non medicated dogs. No immunological reaction against the (allogeneic) seeded endothelial cells were noted. PMID- 8359297 TI - Distal vein graft reconstruction for isolated tibioperoneal vessel occlusive disease in diabetics with critical foot ischaemia--does it work? AB - Since 1986, 75 distal vein bypass procedures have been performed in 72 diabetics with isolated tibioperoneal vessel occlusive disease for limb salvage. Fifty-six grafts were anastomosed proximally to the below-knee popliteal artery and 19 to the anterior tibial artery. Autologous vein was used in all patients. One patient died within the first postoperative month. Of the occluded grafts, only two which failed during hospitalisation were salvaged. In six patients progressive plantar gangrene necessitated below-knee amputation in spite of graft patency. Using life table analysis, primary and secondary patency rates were 84 and 86% at 1 year and 71 and 76% at 5 years. One- and five-year limb salvage rates were 81 and 72%, respectively. Distal vein graft reconstruction for limb threatening ischaemia produces excellent patency rates and contributes significantly to limb salvage in these patients. PMID- 8359298 TI - Lower limb ischaemia in primary antiphospholipid syndrome. AB - Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder manifested by recurrent thrombosis in the venous and arterial system. We report a group of seven patients with lower limb ischaemia associated with PAPS. Four were male patients and three were females, with a mean age of 37 years. All had a previous deep vein thrombosis and the majority, five out of seven, had a prior cerebrovascular accident (CVA). Prolonged activated thromboplastin time was demonstrated in all our patients and PAPS was established by positive thromboplastin titration index, circulating anticoagulant index and increased anticardiolipin levels. Symptoms included claudication in three, rest pain in four and gangrene in five patients. Angiography demonstrated thrombosis of various segments of the arterial tree including: aorta, iliac, femoral and popliteal arteries. Two patients were treated conservatively and one by percutaneous transluminal angioplasty (PTA) of the distal aorta. A total of eleven vascular surgical procedures were performed in four patients resulting in early postoperative thrombosis (2h-30 days) in 10 cases. Only one graft remained patent, when full heparinisation (1000 units/h) was used perioperatively. We conclude that PAPS patients are at high risk for graft thrombosis and should only be operated upon on full anticoagulation, starting at operation and proceeding indefinitely. PMID- 8359299 TI - Chronic critical leg ischaemia must be redefined. AB - The Second European Consensus Document on Chronic Critical Leg Ischaemia defines critical limb ischaemia in non-diabetic patients as rest pain or tissue necrosis (ulceration or gangrene) with an ankle systolic pressure (ASP) of less than or equal to 50 mmHg, or a toe pressure of less than or equal to 30 mmHg. The aim of this study was to investigate whether this definition is able to predict the outcome of patients with severe lower limb ischaemia and thus to determine the relevance of the definition in clinical practice. We have analysed 148 severely ischaemic limbs in 133 non-diabetic patients who presented with rest pain, tissue necrosis or a combination of these symptoms. Fifty-one percent of these limbs fulfilled the current definition with an ASP < or = 50 mmHg; 49% had an ASP > 50 mmHg and were thus not defined as critically ischaemic according to the current definition. We have compared actuarial limb salvage and mortality rates in patients with an ASP < or = 50 mmHg to those patients with an ASP > 50 mmHg. The 1 year limb salvage and mortality rates for ischaemic limbs fulfilling the European Consensus Document criteria were 78.7 and 36.7% respectively, compared to rates of 73.9 and 17.3% in patients who were not defined as critically ischaemic under the current definition. There were no significant differences between 1 year limb salvage or mortality rates between the two patients groups (p = 0.843, 0.078, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359301 TI - Prevalence of symptomatic leg ischaemia in a Swedish community--an epidemiological study. AB - The prevalence of symptomatic leg ischaemia (SLI) was studied using a standardised postal questionnaire and by measuring ankle systolic blood pressure among those with leg pain. All individuals, aged 50-89 years, of both sexes (n = 2748) in a community of 7524 inhabitants were included. The overall questionnaire response rate was 92%, of whom 441 (17%) reported any form of leg pain. Ankle systolic blood pressure (ASBP) was measured in 353 (80%) of those. Ankle/brachial index (ABI) < or = 0.8 was chosen as the criterion for verified SLI. One hundred and seven (30%) had a verified SLI (ABI < or = 0.8). Hospital records could be reviewed in 83% of the non-responders, and revealed corresponding distributions of risk factors among the non-responders and the questionnaire-responders. Risk factor frequencies among ASBP-examined and not examined individuals were also comparable. The overall prevalence of SLI in the age 50-89 years was 4.1%, ranging from 1.5% in the age decade of 50-59 years, to maximum 7.1% in the decade 70-79 years. A slight but not significant male predominance was recorded, except for the age decade 70-79 years. The prevalence of SLI in the whole community population was approximately 2000/100,000 of which 5% were possible candidates for vascular intervention. PMID- 8359300 TI - How much heparin? A simple in vitro test. AB - A simple in vitro test to calculate the dose of heparin required to achieve optimal in vivo anticoagulation during surgery has been assessed in 15 patients who subsequently underwent vascular surgery. Heparin was added to four aliquots of patients blood in vitro to give five solutions with heparin concentrations ranging from 0-0.8 units/ml of plasma. The activated partial thromboblastic times (APTT) of each of these samples was then measured and the natural log (ln) of the APTT calculated. The natural log of the APTT in vitro was then plotted against the in vitro heparin concentration. From this linear correlation the concentration of heparin required to achieve an APTT 2.5 times the normal in vitro (Hc) for the 15 different patients was calculated and ranged from 0.4-0.75 units/ml (median 0.47). Based on an estimate of the plasma volume (PV), the bolus dose of heparin given intravenously to each patient to produce an equivalent anticoagulant response in vivo was calculated (Hc x PB). Heparin boli administered ranged from 1000-2000 units (median 1500). The mean in vivo APTT achieved was 77% of the predicted value (range 62%-123%). Such an estimation of an in vivo response, by means of an in vitro test, should help to more accurately predict the effects of heparin in vivo and individualise anticoagulation dosage. PMID- 8359302 TI - The choice of strategy in the treatment of intermittent claudication--a decision tree approach. AB - OBJECTIVES: to compare possible outcomes of the non-operative treatment for intermittent claudication with that of surgery. DESIGN: decision tree approach using published and vascular registry data. The valuation of clinical outcomes was estimated by index weights using the Rosser index and the Quality of Well Being scale. SETTING: routine health care in Sweden. MATERIALS: published data on 224 non-operatively treated claudicants and data from 805 claudicants treated with surgery or angioplasty from the Swedvasc registry. No diabetics were included. Chief outcome measure: expected utility value at one year after decision on treatment given the clinical data and the estimated health status valuations. MAIN RESULTS: it was possible to identify a success rate for surgery above which it was the better alternative. However, depending on which of two health indices that was used, and if reconstruction was supra- or infrainguinal, this threshold value varied from 0-81%. CONCLUSIONS: reliable measures of the value of outcomes have to be developed and, in addition, long-term data on outcome and costs in routine care have to be collected before a comprehensive economic assessment based on the decision tree approach can be made to support decisions on treatment for intermittent claudication. PMID- 8359303 TI - A prospective study of the natural history of femoropopliteal artery stenosis using duplex ultrasound. AB - A foreknowledge of impending femoral artery occlusion might allow prevention of a deterioration in ischaemia by percutaneous transluminal angioplasty (PTA) in the preocclusive stage. A window of opportunity exists before a femoral stenosis progresses to occlusion and its treatment by PTA becomes more difficult, riskier and associated with lower patency. The size of this window is unknown. This is the first report of a study of the natural history of femoral stenoses using Duplex ultrasound. The aims of the study were to determine in patients with symptomatic peripheral arterial disease: (1) the incidence of progression from stenosis to occlusion; (2) the change in severity of stenosis over time; and (3) the relationship between severity of stenosis and progression to occlusion. The velocity ratio (VR) of 43 femoral artery stenoses in 38 patients was measured by Duplex ultrasound. The examination was repeated after a median of 28 (range 5-76) weeks. Nine/43 (21%) stenoses progressed to occlusion within a median of 13 weeks. Little overall change in VR was demonstrable if occlusion did not occur. Only stenoses with a VR > 3 progressed to occlusion in the study period. The data suggest that severe stenoses progress more rapidly than moderate, with a relatively brief window of opportunity. If PTA is to be undertaken, stenoses with a VR greater than 3 should be treated with minimum delay. PMID- 8359304 TI - Quality of life following lower limb amputation for peripheral arterial disease. AB - Lower limb amputations for peripheral arterial disease are performed predominantly on an elderly population with poor social support and concomitant medical problems. The effect of amputations on the quality of life of this population has not been properly assessed. The quality of life of 149 amputees from one hospital was evaluated using the Nottingham Health Profile and compared to that of a control group matched for age and sex. One hundred and thirty (87%) amputees and 115 (77%) controls responded to the questionnaire. Amputees reported significantly more problems with mobility, social isolation, lethargy, pain, sleep and emotional disturbance than controls (p < 0.001). However, mobility was the only significant independent factor after matched logistic regression analysis (p < 0.001). The differences in social isolation and emotional distress lost their significance after adjustment for mobility. The overall quality of life following lower limb amputation for peripheral arterial disease is poor, but much of this is secondary to restricted mobility. Rehabilitation following amputation should therefore focus on attempts to improve mobility. PMID- 8359305 TI - A simple technique for thrombectomy of a reversed saphenous vein arterial bypass graft. PMID- 8359306 TI - A new posterior approach for an extra-anatomical arterial bypass for lower extremity revascularisation (gluteopopliteal bypass). PMID- 8359307 TI - The basilic vein as an in situ bypass for occlusion of the brachial artery. AB - The use of the basilic vein as an in situ bypass in upper extremity revascularisation has not as yet been reported. Two patients with an occlusion of the brachial artery and disabling arm claudication in whom the basilic vein was a suitable vascular conduit are discussed. PMID- 8359308 TI - Basilic vein in situ bypass for chronic post-traumatic ischaemia of the arm. PMID- 8359309 TI - Penetrating missile embolisation. AB - The present case report is that of a 13-year-old boy, who was admitted to the Emergency Unit at the American University of Beirut Medical Center (AUBMC), with a bullet injury to the right upper quadrant with no exist. Chest X-ray and KUB failed to reveal the bullet and there was no evidence of haemo- or pneumothorax. X-ray of both thighs showed the bullet at the level of the right groin. The bullet penetrated the liver, diaphragm and pericardium. It entered through the left ventricle and embolised through the arterial circulation to the right superficial femoral artery. Included in this report is a review and analysis of patients with missile embolisation, who were treated at the AUBMC over the last 10 years. PMID- 8359310 TI - Upper limb venous gangrene, a lethal condition. AB - Venous gangrene of the upper extremity is rare. It was the mode of presentation in a 41-year-old woman who died 10 days later of heart failure due to acute myocardial infarction. There is evidence from this and previous publications that patients with this condition tend to have characteristics in common. Most have either advanced malignant disease or seriously impaired myocardial function and venous gangrene usually occurs as a pre-terminal event. Treatment should be directed primarily at the underlying illness but there may be a case for early amputation if permitted by the general condition of the patient. PMID- 8359311 TI - Workshop on the scientific evaluation of the safety factor for the acceptable daily intake (ADI): editorial summary. PMID- 8359312 TI - Data-derived safety factors for the evaluation of food additives and environmental contaminants. AB - A safety factor of 100-fold is commonly applied to animal data to derive the acceptable daily intake (ADI) of food additives; other factors have been used in some cases and higher values are used more frequently for determining the tolerable daily intake (TDI) of environmental chemicals. The 100-fold factor is considered to represent the product of a 10-fold factor to allow for species differences between the test animal and humans and a 10-fold factor to allow for inter-individual differences. A scheme is proposed whereby data relevant to the safety assessment of a compound, e.g. species differences in toxicokinetics, can contribute quantitatively to the safety factor and therefore to the ADI or TDI. For this to be possible, it is necessary to subdivide each of the 10-fold factors into two separate factors to allow for differences in toxicokinetics and toxicodynamics. For any compound, data on one particular aspect may be used to derive a specific data-derived factor for that aspect. The overall safety factor will then be calculated as the product of the known data-derived factor(s) and default values for the remaining unknown factors. In this way the derivation of the safety factor would be clearly defined and the potential impact of additional data on other aspects identified. Additional safety factors (over and above the 100-fold or overall data-derived factor) are also proposed to allow for the nature or severity of the toxicity and the adequacy of the database. These factors are consistent with previous evaluations and will allow the logical derivation of factors greater than either 100 or the appropriate data-derived factor. These additional factors will be of greatest value in the derivation of safety factors for the calculation of the TDIs of environmental contaminants but may also be applied if necessary to the safety assessment of food additives. In such cases the rationale and logic for a safety factor in excess of 100 will be clearly defined. PMID- 8359313 TI - Scientific evaluation of the safety factor for the acceptable daily intake (ADI). Case study: butylated hydroxyanisole (BHA). AB - The principles of 'data-derived safety factors' are applied to toxicological and biochemical information on butylated hydroxyanisole (BHA). The calculated safety factor for an ADI is, by this method, comparable to the existing internationally recognized safety evaluations. Relevance for humans of forestomach tumours in rodents is discussed. The method provides a basis for organizing data in a way that permits an explicit assessment of its relevance. PMID- 8359314 TI - Hazard assessment of lead. AB - Exposure to lead (Pb) continues to be a source of concern for the US Food and Drug Administration and other United States federal regulatory agencies. Blood lead levels as low as 10 micrograms/dl have been associated with impaired neurobehavioural and cognitive development and electrophysiological deficits in children and reduced gestational age and birth weight in infants. Blood lead levels of 10 micrograms Pb/dl are also of concern in pregnant women because of exposure to the fetus. Blood lead levels of 30 micrograms Pb/dl have been associated with elevated blood pressure and other adverse effects in adults. Thus, the values of 10 and 30 micrograms Pb/dl represent lowest-observed-effects levels for developing and adult populations, respectively. The ingestion levels that result in these blood levels of concern were estimated to be 60 micrograms Pb/day for children ages 6 years or younger, 150 micrograms Pb/day for children aged 7 years or older, 250 micrograms Pb/day for pregnant women and 750 micrograms Pb/day for adults. Provisional total tolerable intake levels for lead were derived from these blood lead levels for each group by applying the Renwick approach to obtain a tolerable exposure level. PMID- 8359315 TI - A data-derived safety (uncertainty) factor for the intense sweetener, saccharin. AB - An increased incidence of bladder cancer is found when male rats are fed high dietary concentrations of sodium saccharin (3% or more) from birth. This toxicity has been used as the basis for the development of a data-derived safety factor. Such an effect would attract an extra factor (10-fold) for nature of toxicity and in the absence of other data would result in a high overall safety factor. However the extensive mechanistic database on sodium saccharin allows an assessment of the potential relevance of the effect for humans. In addition the effect is only seen under specific conditions in rats, i.e. largely with the sodium salt and with a commercial rat diet. The effect is not related to the concentration of saccharin in the rat urine or bladder so that toxicokinetic considerations are simplified. The extensive animal database allows the determination of data-derived factors for inter-species differences in both toxicokinetics and toxicodynamics. Based on this analysis an overall safety factor of 50 (which includes the factor of 10 for severity of effect) would appear appropriate at the present time. This factor, and the ADI which would result from its application, are consistent with the absence of an association between the consumption of artificial sweeteners and bladder cancer in humans. PMID- 8359316 TI - The evaluation of data-derived safety factors for bis(tri-n-butyltin)oxide. AB - In this report the evaluation of a safety factor is assessed, according to the decision tree suggested by Renwick (1991a,b), to determine a Tolerable Daily Intake (TDI) value for the environmental contaminant bis(tri-n-butyltin)oxide (TBTO). Based on available literature the nature of the most sensitive parameter of TBTO-toxicity was perceived to be on lymphoid organs and lymphoid function. Subsequently, safety factors were derived in relation to published data on inter species and inter-individual differences in both kinetics and dynamics of TBTO. Lack of information on human data concerning the nature of toxicity as well as kinetics and dynamics of TBTO finally resulted in a safety factor of 100. A TDI of 5 or 0.25 mg/kg bw per day was assessed based on reductions of lymphoid organ weights (thymus) or lymphoid function (resistance to T. spiralis), respectively. In addition, based on available data in rodents on kinetics and dynamics of TBTO, it is suggested that a combined TDI value for both tri- and dibutyltin compounds might have to be considered. PMID- 8359318 TI - Why some new ideas fail. PMID- 8359319 TI - Trusted employee stole more than cash. PMID- 8359317 TI - Scientific evaluation of the data-derived safety factors for the acceptable daily intake. Case study: diethylhexylphthalate. AB - Diethylhexylphthalate causes peroxisome proliferation and is hepatocarcinogenic in rodents; it also displays reproductive and developmental toxicity in a variety of mammalian and non-mammalian species. These manifestations of toxicity have each been separately evaluated for the development of a data-derived safety factor and Tolerable Daily Intake (TDI). Using hepatocarcinogenicity as the pivotal study, the nature of toxicity factor of 10 is applicable and there are no adequate studies demonstrating a No-Observed-Adverse-Effect Level (NOAEL). If studies of less statistical sensitivity are used to derive the NOAEL and a factor of 0.1 is used for the relative sensitivity to humans of peroxisome proliferation (assuming this is linked mechanistically to carcinogenesis), a TDI of 1 mg/kg bw is obtained. The data-derived safety factor using peroxisomal proliferation as the pivotal end-point is 6.25, since the factor from trans-species toxicodynamics is 0.01, and the TDI derived from the NOAEL for peroxisome proliferation is thus 8 mg/kg bw. If teratogenicity is used as the pivotal study, the nature of toxicity attracts a factor of 10 and all the other aspects take default values because of the limited availability of relevant toxicodynamic and toxicokinetic data. The TDI derived from the NOAEL for teratogenicity is then 0.04 mg/kg bw and this confirms teratogenicity as the limiting aspect of toxicity defining the TDI. It also identifies the fact that appropriate toxicokinetic and toxicodynamic data related to the pregnant animal and fetus would facilitate a re-evaluation of the safety factor and TDI by replacing the current default values by data-derived values. PMID- 8359320 TI - Maximize your financing program. PMID- 8359321 TI - Overcoming some common situations, common barriers. PMID- 8359322 TI - Expanding to meet practice growth. PMID- 8359323 TI - Sounding board for complaints. PMID- 8359324 TI - Where there's a will, should there be a trust? PMID- 8359325 TI - OSHA: bad business or new opportunity? PMID- 8359326 TI - Marketing excellence with quality provisional restorations. PMID- 8359327 TI - Impression excellence through precise gingival retraction. PMID- 8359329 TI - The clinical assistant's role in the new-patient examination. PMID- 8359328 TI - Monitoring "the vital signs" of masticatory system health--a simplified screening for TM problems. PMID- 8359330 TI - Productivity in endodontics. PMID- 8359331 TI - Regulations needed for implantology. PMID- 8359332 TI - A playful, active practice setting. PMID- 8359334 TI - Push without shove. PMID- 8359333 TI - The keys to a successful practice. PMID- 8359335 TI - Sealants: an underused service. PMID- 8359336 TI - Realizing the dream. PMID- 8359337 TI - Coping with increasing regulations. PMID- 8359338 TI - Taking a risk. PMID- 8359339 TI - Increasing practice quality and productivity through high-retention, low-wear sealants. PMID- 8359341 TI - Esthetic excellence with implant abutments. PMID- 8359340 TI - Esthetic excellence with the single-tooth implant. PMID- 8359342 TI - Peri-implantitis versus periodontitis. PMID- 8359343 TI - Retrobulbar histology and immunohistochemistry in endocrine ophthalmopathy. PMID- 8359344 TI - Graves' hyperthyroidism and endocrine ophthalmopathy--one or two closely related diseases? PMID- 8359346 TI - Autoimmune endocrine ophthalmopathy--the ophthalmologist's view. PMID- 8359345 TI - Immunogenetics of endocrine ophthalmopathy and Graves' disease. PMID- 8359347 TI - Immunosuppression in endocrine ophthalmopathy: why and when? PMID- 8359348 TI - Orbital radiotherapy in the treatment of endocrine ophthalmopathy: when and why? PMID- 8359349 TI - Orbital decompression for endocrine ophthalmopathy: the endonasal approach. PMID- 8359350 TI - T cell reactivity in endocrine ophthalmopathy. PMID- 8359351 TI - Biological activity of antibodies circulating in endocrine ophthalmopathy. PMID- 8359352 TI - Elevated anti-alpha-galactosyl antibody titres. A marker of progression in endocrine ophthalmopathy and in auto-immune thyroid disorders? PMID- 8359353 TI - Orbital connective tissue in endocrine ophthalmopathy. PMID- 8359354 TI - Urinary and plasma glycosaminoglycans in endocrine ophthalmopathy. PMID- 8359355 TI - Adipose tissue in endocrine ophthalmopathy. PMID- 8359356 TI - Nature and significance of eye muscle autoantigens in endocrine ophthalmopathy. PMID- 8359357 TI - Eye muscle cells in endocrine ophthalmopathy. PMID- 8359358 TI - Mouse monoclonal antibodies to human and bovine xanthine oxidase (XO). PMID- 8359359 TI - Antibodies to xanthine oxidase (XO) in human males and females. PMID- 8359360 TI - Sensitive enzyme linked immunosorbent assay (ELISA) for xanthine oxidase. PMID- 8359361 TI - The effects of high monounsaturated and polyunsaturated fat diets on vascular endothelium and the coagulation system in non-insulin dependent diabetes mellitus -related to changes in lipid peroxidation? PMID- 8359362 TI - Doctoral studies at a British university and at a Pakistani university: a comparison. PMID- 8359363 TI - The effects of tetrahexylammonium chloride on calcium mobilization from cerebellar microsomes. PMID- 8359364 TI - Effects of allethrin on the thermotropic properties of phospholipid vesicles. PMID- 8359365 TI - Molecular forms of acetylcholinesterase in microsomal membranes of normal and dystrophic muscle. PMID- 8359366 TI - Control of insulin secretion by imidazolines in rat pancreatic islets. PMID- 8359367 TI - L-trans-pyrrolidine-2,4-dicarboxylic acid (L-transPDC) has properties consistent with that of a competitive substrate for the plasma membrane glutamate transporter. PMID- 8359368 TI - WAY 100252 inhibits evoked [3H]GABA release when tested against a number of release-inducing stimuli. PMID- 8359369 TI - The role of His394 in the binding of substituted benzamides to the rat D2 dopamine receptor. PMID- 8359370 TI - Overexpression of the D2 dopamine receptor in insect cells using the baculovirus system. PMID- 8359371 TI - Pharmacological characterization of the human serotonin 5-HT-1A receptor expressed in CHO cells using the ergot alkaloids lisuride. PMID- 8359372 TI - Expression of the rat D2 dopamine receptor in the yeast Saccharomyces cerevisiae. PMID- 8359374 TI - Localisation of agonist stimulated CMP-phosphatidate accumulation in single mammalian neurones. PMID- 8359373 TI - Neocortical neuronal polarity: targeting of a foreign protein linked to a glycosyl-phosphatidylinositol (GPI) anchor in postmitotic neurons and polarized distribution of a marker of the trans-Golgi network (TGN 38). PMID- 8359375 TI - An isoform of the cGMP-gated retinal photoreceptor channel gene expressed in the sinoatrial node (pacemaker) region of rabbit heart. PMID- 8359376 TI - Nuclear associated casein kinase II expression in rat ventral prostate. PMID- 8359377 TI - Diabetes-related changes in sialic acid content of leucocytes: an assay-dependent artefact? PMID- 8359378 TI - Beta-cell responses in the offspring of non-insulin dependent diabetics after a test meal. PMID- 8359379 TI - Homologous sequences in fibrillar collagens may be proteoglycan binding sites. PMID- 8359380 TI - The role of glycogenin in glycogen synthesis and non-insulin dependent diabetes mellitus. PMID- 8359381 TI - Intracellular events in the assembly and secretion of apolipoprotein B in rat liver. PMID- 8359382 TI - Topography of apolipoprotein B in subcellular fractions from rabbit liver. PMID- 8359383 TI - Apolipoprotein (a) in rabbit blood and liver. PMID- 8359384 TI - Serum factors that regulate phagocytosis of liposomes by Kupffer cells. PMID- 8359385 TI - Phosphorylation of apoproteins in VLDL and LDL by protein kinases in vitro. PMID- 8359386 TI - Valinomycin pretreatment induced LDL receptor activity in cultured human cells. PMID- 8359387 TI - Direct visualization of lipid vesicle changes on addition of filamin. PMID- 8359388 TI - Comparison of the purification of lipoprotein lipase from various rat tissues. PMID- 8359389 TI - Glucose dependent insulinotropic polypeptide and glucagon-like peptide-1(7 36)amide: effects on lipoprotein lipase activity. PMID- 8359390 TI - Measurement of postprandial apolipoprotein B-48 using a novel specific antibody. PMID- 8359391 TI - The use of retinyl palmitate to measure clearance of chylomicrons and chylomicron remnants following meals of different fatty acid compositions. PMID- 8359392 TI - Evidence for a regulatory link between hepatic lipase secretion and intra hepatocyte cholesterol. PMID- 8359393 TI - Conformational changes in oxidized LDL using X-ray and neutron solution scattering techniques. PMID- 8359394 TI - The effects of native and oxidised low density lipoproteins on platelet activation. PMID- 8359395 TI - Altered interactions between lipogenesis and glycogenesis in liver during fructose feeding. PMID- 8359396 TI - Cardiac lipoprotein lipase activities in relation to glucose utilization during progressive starvation. PMID- 8359397 TI - Factors contributing to the hypertriacylglycerolaemia of late pregnancy. PMID- 8359399 TI - Adipose tissue site specificity of lipoprotein lipase mRNA expression in rats fed diets containing different fatty acid compositions. PMID- 8359398 TI - Effects of niacin on biliary lipid output in the rat. PMID- 8359400 TI - Reverse cholesterol transport from the perfused spleen in the presence or absence of a perfused liver. PMID- 8359401 TI - Plasma VLDL cholesterol and egg cholesterol are resistant to change in the laying hen. PMID- 8359402 TI - Cholesterol feeding increases serum VLDL and hepatic phosphatidate phospohydrolase in hamsters. PMID- 8359403 TI - Depot specific effects of insulin and isoproterenol on porcine adipose tissue metabolism. PMID- 8359404 TI - LDL binding to hepatocytes isolated from hamsters fed different dietary fatty acids. PMID- 8359405 TI - A lipophilic protein inhibitor of neutral cholesteryl ester hydrolase: effects of treatment with female sex hormones. PMID- 8359406 TI - Assessment of particle size of very low density lipoproteins by morphometry. PMID- 8359407 TI - Very low density lipoprotein apo beta 100--comparison of several methods for protein assay. PMID- 8359408 TI - The effect of dietary casein and soyprotein on cholesterol metabolism in hamsters. PMID- 8359409 TI - Control of lipoprotein lipase activity by isoproterenol. PMID- 8359410 TI - In vitro testing of a glyoxalase I inhibitor. PMID- 8359411 TI - Modification of the glyoxalase system in clinical diabetes mellitus. PMID- 8359412 TI - Inhibition of human leukaemia 60 cell growth by diethyl esterification of the glyoxalase II inhibitor S-p-nitrobenzoxycarbonylglutathione in vitro. PMID- 8359413 TI - The potentiation of GTP-dependent assembly of microtubules by S-D lactoylglutathione. PMID- 8359414 TI - The effect of S-D-lactoylglutathione on the movement of neutrophils. PMID- 8359415 TI - Modification of the glyoxalase system in streptozotocin-induced diabetic rats and the effect of the aldose reductase inhibitor Statil. PMID- 8359416 TI - Formation of methylglyoxal and D-lactate in human red blood cells in vitro. PMID- 8359417 TI - The assay of S-D-lactoylglutathione in biological systems. PMID- 8359418 TI - Inhibition of growth of human leukaemia 60 cells by S-2-hydroxyacylglutathione derivatives. PMID- 8359419 TI - Mechanism of the inhibition of growth of human leukaemia 60 cells by S-D lactoylglutathione. PMID- 8359420 TI - Glyoxalase activity in human tumour cell lines in vitro. PMID- 8359421 TI - Inhibition of proliferation of human leukaemia 60 cells by methylglyoxal in vitro. PMID- 8359422 TI - The hydrolysis of S-D-lactoylglutathione. PMID- 8359424 TI - Simple chromatographic methods for the purification of human red blood cell glyoxalase I and glyoxalase II to homogeneity. PMID- 8359423 TI - Binding of methylglyoxal to albumin and formation of fluorescent adducts. Inhibition by arginine, N-alpha-acetylarginine and aminoguanidine. PMID- 8359425 TI - Population genetics of human glyoxalases and the development of diabetic complications. PMID- 8359426 TI - In situ kinetics of yeast glyoxalase I. PMID- 8359427 TI - Oxygen effects on yeast glyoxalase system. PMID- 8359428 TI - Structural characterisation of human caeruloplasmin in solution by FTIR spectroscopy. PMID- 8359429 TI - Quantitative analysis of defects of mitochondrial oxidation during recovery from exercise. PMID- 8359430 TI - Control of intracellular concentrations of 'bioenergetic' metabolites in skeletal muscle. PMID- 8359431 TI - Theoretical aspects of transient disturbances of cellular [Pi] and organic phosphates. PMID- 8359432 TI - Skeletal muscle Pi transport in vitro. PMID- 8359433 TI - Transarcolemmal Pi movement in perfused rat heart: a 31-P NMR spectroscopic study. PMID- 8359434 TI - Use of olive cultures to evaluate triacylglycerol synthesis. PMID- 8359435 TI - Influence of alterations in environmental CO2 and temperature on wheat grain lipids. PMID- 8359436 TI - Differential sensitivity of lipid metabolism in monocotyledons to grass-specific herbicides. PMID- 8359438 TI - Further studies on Plasmodium falciparum glycoproteins: characterization of 195 kDa glycoprotein. PMID- 8359437 TI - The inhibition of fatty acid elongation by a thiocarbamate herbicide and its sulphoxide. PMID- 8359439 TI - Further studies on cervical glycoproteins: isolation and characterization of oligosaccharides from follicular phase cervical glycoproteins of bonnet monkey. PMID- 8359440 TI - Thymidylate synthase in normal and cancer tissues. PMID- 8359441 TI - Partial purification of ribose 1-phosphate dependent "ADP forming" activity in rat liver. PMID- 8359442 TI - Purine nucleotide catabolism in rat liver. PMID- 8359443 TI - Estradiol and phospholipid metabolism in the rat. PMID- 8359444 TI - Purine nucleotide content of lymphocytes subpopulations. PMID- 8359445 TI - Protein kinase C alpha is the isoform responsible for inhibition of histamine H2 receptor mediated stimulation of adenylate cyclase in the human gastric cancer cell line HGT-1. PMID- 8359446 TI - Short term effects of interleukin-1 beta on insulin secretion and cyclic nucleotide levels in rat islets of Langerhans cultured with arginine and arginine analogues. PMID- 8359447 TI - The solubility of Coomassie blue protein-dye complexes. PMID- 8359448 TI - SDS-PAGE of cat parotid salivary proteins. PMID- 8359449 TI - Effects of atropine upon the secretion of rate parotid salivary proteins. PMID- 8359450 TI - A monoclonal antibody which recognizes rabbit CD11a and which inhibits homotypic T cell aggregation. PMID- 8359451 TI - Isolation and characterization of a novel family of G protein-coupled receptors. PMID- 8359452 TI - Solubilisation and molecular characterisation of the P2X purinoceptor. PMID- 8359453 TI - Gene expression and control of enzymes for synthesis of magnesium protoporphyrin monomethyl ester in Rhodobacter sphaeroides. PMID- 8359454 TI - The cloning and overexpression of E. coli acyl carrier protein (ACP). PMID- 8359455 TI - Mucosal surface ferricyanide reductase in mouse duodenum. PMID- 8359456 TI - Cytosolic aconitase activity in mouse small intestine: iron dependence. PMID- 8359457 TI - Degradation of human and rat surfactant apoprotein by neutrophil elastase and cathepsin G. PMID- 8359458 TI - Alpha-1-proteinase inhibitor activity can be compromised by the choice of assay conditions. PMID- 8359459 TI - The antigenicity of elastin-derived peptides obtained from atherosclerotic human aorta. PMID- 8359460 TI - Immunospecificity of soluble elastin peptides: determination by ELISA assay. PMID- 8359461 TI - The effect of arginine on glycolysis by Streptococcus mutans and Actinomyces viscosus. PMID- 8359462 TI - Analysis of enterotoxin synthesis in a Vibrio cholerae strain lacking DsbA, a periplasmic enzyme involved in disulphide bond formation. PMID- 8359463 TI - A new method for the purification of the B subunit (EtxB) of Escherichia coli heat-labile enterotoxin. PMID- 8359464 TI - Monosaccharide composition of haptoglobin purified from alcoholic cirrhotic and control sera determined by HPAE. PMID- 8359465 TI - New substrate-derived thiol-specific time-dependent inhibitors for the characterisation of the coupling of binding site interactions with catalytic site chemistry in the cysteine proteinases. PMID- 8359467 TI - The kinetically influential ionizations of chymopapain M. PMID- 8359466 TI - Ficin: a cysteine proteinase with binding site-catalytic site signalling characteristics intermediate between those of papain and actinidin. PMID- 8359468 TI - Nature of the leak induced in erythrocyte membranes by Kanagawa Haemolysin. PMID- 8359469 TI - Effect of a milk fat globule membrane fraction on cultured mouse mammary cells. PMID- 8359470 TI - Free radical damage in Down's syndrome brain. PMID- 8359471 TI - Catalytic RNA: structure and mechanism. PMID- 8359472 TI - Lipid sorting--measurement and interpretation. PMID- 8359473 TI - Biosynthesis of sphingomyelin and its delivery to the surface of baby hamster kidney (BHK) cells. PMID- 8359474 TI - Properties and intracellular localization of phosphatidylinositol transfer protein in Swiss mouse 3T3 cells. PMID- 8359475 TI - Mechanism and function of changes in membrane-phospholipid asymmetry in platelets and erythrocytes. PMID- 8359476 TI - Biocompatible surfaces based upon the phospholipid asymmetry of biomembranes. PMID- 8359477 TI - Two-phase partitioning applied to changes in phospholipid asymmetry. AB - In summary aqueous two-phase polymer partition is a useful addition to the range of techniques available for determining lipid asymmetry in model and in biological membrane systems. The methodology is straightforward, the experimental requirements simple and the materials used inexpensive. We have demonstrated its usefulness in several model membrane systems rendered asymmetric by the establishment of a membrane potential across the lipid bilayer and in monitoring Ca(2+)-induced asymmetry in human erythrocytes. PMID- 8359478 TI - Structure and energetics of phospholipid and diacylglycerol assemblies relative to membrane fusion. PMID- 8359479 TI - Asymmetry in trans-bilayer lateral pressure may drive expansion of the secretion fusion pore. PMID- 8359480 TI - How lipid asymmetry can make vesicles fusion-competent by inhibition of the thermal undulations. PMID- 8359481 TI - Loss of phospholipid asymmetry in cell fusion. PMID- 8359482 TI - Diacylglycerol in the exocytosis of the mammalian sperm acrosome. PMID- 8359483 TI - Protein kinase C, membrane fusion and platelet granule secretion. PMID- 8359484 TI - Molecular studies on chemotactic receptors. PMID- 8359485 TI - Identification of a protein capable of causing fusion of endosome and lysosome membranes. PMID- 8359487 TI - Structural analysis of the variation in the major outer membrane proteins of Neisseria meningitidis and related species. PMID- 8359486 TI - Sequence-specific anti-peptide antibodies that recognize different subunits of the high-affinity IgE receptor. PMID- 8359488 TI - Characterization of amino-acid transport in pig erythrocytes. PMID- 8359489 TI - GLUT 1: identification of exofacial lysine-residues. PMID- 8359490 TI - Dynamics of lipid peroxidation and its inhibition by antioxidants. PMID- 8359491 TI - Cerebral ischaemia, free radicals and antioxidant protection. PMID- 8359492 TI - High-dose systemic iron chelation attenuates reperfusion injury. PMID- 8359493 TI - Composition and organization of the NADPH oxidase of phagocytes and other cells. PMID- 8359494 TI - Protein modification by oxidants and the role of proteolytic enzymes. PMID- 8359496 TI - Peroxynitrite and atherosclerosis. PMID- 8359495 TI - Mitochondrial calcium handling and oxidative stress. PMID- 8359497 TI - Antioxidant drugs and the inhibition of low-density lipoprotein oxidation. PMID- 8359499 TI - Oxidative stress and its control: a pathogenetic role in inflammatory joint disease. PMID- 8359498 TI - Free radicals and mitochondrial dysfunction in Parkinson's disease. AB - The precise relationship of the complex I deficiency in PD to the dopaminergic cell death and aetiology of this disorder is as yet unknown. However, evidence is accruing that this mitochondrial defect may play a central role in the cascade of events that terminates in nigral neuronal loss. Further work needs to be carried out to determine the molecular mechanisms that underlie the complex I deficiency as these may provide important indicators to the ultimate cause of PD. This may involve a genetic abnormality of complex I that may convey a susceptibility to developing PD. Alternatively, exogenous or endogenous toxic agents may target nigral complex I along pathways similar to those recognized for MPTP. A combination of a genetic predisposition in addition to an environmental precipitant has gained substantial support as an explanation for the cause of PD. PMID- 8359500 TI - Review of General Medical Council proposals on undergraduate medical education. PMID- 8359501 TI - Contribution of basic medical science to a new medical curriculum. PMID- 8359502 TI - Teaching versus learning. PMID- 8359503 TI - Two revolutions and the scientific culture. PMID- 8359504 TI - Identification of cytosolic protein regulators of exocytosis. PMID- 8359505 TI - Hippocampal nicotinic autoreceptors modulate acetylcholine release. PMID- 8359506 TI - Probing the atomic interactions between proteins and carbohydrates. PMID- 8359507 TI - Oligosaccharides and recognition--a 'shape' problem probed by n.m.r. and molecular modelling. PMID- 8359508 TI - The conformational effects of N-linked glycosylation. PMID- 8359509 TI - Recognition of complex carbohydrates by Ca(2+)-dependent animal lectins. PMID- 8359510 TI - Sweet and shapely: ligands for animal lectins. PMID- 8359511 TI - Structure/function relationships in the collectins (mammalian lectins containing collagen-like regions). PMID- 8359512 TI - Recognition of complex carbohydrates by the macrophage mannose receptor. PMID- 8359513 TI - The role of mannose-binding protein in host defence. PMID- 8359514 TI - Heparan sulphate: functional role as a modulator of fibroblast growth factor activity. PMID- 8359515 TI - Apolipoproteins E and C-III have opposing roles in the clearance of lipoprotein remnants in transgenic mice. PMID- 8359516 TI - The assembly and secretion of apoB-100-containing lipoproteins. PMID- 8359517 TI - Synthesis and secretion of apolipoprotein A-I. PMID- 8359518 TI - Genetic influences on lipoprotein(a) concentration. PMID- 8359519 TI - Lipoprotein metabolism in lipase deficient states: studies in primary and secondary hyperlipidaemia. PMID- 8359521 TI - Regulation of lipoprotein lipase. PMID- 8359520 TI - Phenotypic variation of mutations in the human lipoprotein-lipase gene. AB - We have described a large number of different mutations in the LPL gene that result in completely catalytically defective LPL protein. More recently exonic polymorphisms in the LPL gene have been described that do not result in the catalytic activity of LPL being significantly impaired. Furthermore we have recently described a patient who is homozygous for a mutation in the LPL gene in a conserved region of exon 5 that results only in partial residual activity and a very mild clinical phenotype. This may suggest that the frequency of mutations in the LPL gene is greater than has been previously recognized. Recognition and selection of patients for analysis was based on the phenotype of chylomicronaemia. However, the existence of the Ser172-Cys mutation in the LPL gene that results in only moderate hypertriglyceridaemia in the absence of environmental factors might suggest that mutations in this gene are more frequent and could be seen in patients with a milder clinical phenotype. The clue to detecting these changes in the LPL gene might be to investigate patients who present with chylomicronaemia due to different environmental triggers while, in the absence of these environmental factors, they have only moderate hypertriglyceridaemia. PMID- 8359522 TI - Catalytic and molecular properties of glyoxalase I. PMID- 8359523 TI - Glyoxalase I in micro-organisms: molecular characteristics, genetics and biochemical regulation. PMID- 8359524 TI - Glyoxalase II: molecular characteristics, kinetics and mechanism. AB - The mechanism that has been proposed for glyoxalase II [36] is summarized in Figure 3. It involves direct nucleophilic attack of an active-site histidine on the thiol ester substrate to form an acyl-imidazole intermediate which then rapidly hydrolyses. This is consistent with the known susceptibility of thiol esters to aminolysis and with the lability of acyl-imidazoles [47]. PMID- 8359525 TI - The glyoxalase system in higher plants: regulation in growth and differentiation. PMID- 8359526 TI - Modification of the glyoxalase system in disease processes and prospects for therapeutic strategies. PMID- 8359527 TI - Inhibitors of glyoxalase I: design, synthesis, inhibitory characteristics and biological evaluation. PMID- 8359528 TI - Structural relationships between glyoxalase I and membrane transport proteins. PMID- 8359529 TI - Inhibitors and inhibition studies of mammalian glyoxalase II activity. PMID- 8359530 TI - Mechanism for the formation of methylglyoxal from triosephosphates. PMID- 8359531 TI - Fourier transform infrared spectroscopic studies on human transferrin receptor. PMID- 8359532 TI - Inhibition of aminophospholipid translocation in red cell vesicles. PMID- 8359533 TI - Hydrophilic and hydrophobic surface map analysis of bacteriorhodopsin. PMID- 8359534 TI - Effect of heat on 1,2-diacylglycerol and triacylglycerol levels in WRK-1 and CHO cells. PMID- 8359535 TI - Interaction of myosin with charged membranes is affected by ATP. PMID- 8359536 TI - The structure of a polypeptide corresponding to the pore region of the voltage gated potassium channel. PMID- 8359537 TI - Conformation of the Pf1 coat protein in the phage and in a lipid membrane. PMID- 8359538 TI - Binding-independent fluorescence enhancement of MC 540 in erythrocytes with decreased phospholipid asymmetry. PMID- 8359539 TI - Maintenance of GSH content in primary astrocyte cultures under oxidative stress conditions. PMID- 8359540 TI - Diphenylisobenzofuran (DPBF) follows the dynamics of ROO. to RO. and C-centered radicals in microsomal membranes. PMID- 8359541 TI - Detection of radicals in oxidised lipoproteins. PMID- 8359542 TI - The effect of lipid hydroperoxides on the copper dependent oxidation of low density lipoprotein. PMID- 8359543 TI - Short and long term modulation of oxidant induced ATP depletion--implications for effective treatment. PMID- 8359544 TI - Effect of folates and folate antagonists on lipid peroxidation. PMID- 8359545 TI - Alterations in the antioxidant defense of peripheral nervous tissue following acute ethanol administration. PMID- 8359546 TI - Metal-catalysed oxidation and post-Amadori reactions of serum albumin and other model proteins. PMID- 8359547 TI - Erythrocyte-induced oxidation of low density lipoproteins: control by antioxidant nutrients. PMID- 8359548 TI - A new method for measuring antioxidant activity. PMID- 8359549 TI - Novel hydroxamates and myocardial reperfusion injury. PMID- 8359550 TI - The role of bound lipid and transition metal in the formation of fluorescent advanced glycation endproducts by human serum albumin. PMID- 8359552 TI - Purification of xanthine oxidase from human heart. PMID- 8359551 TI - Effect of oxidants on vascular smooth muscle proliferation. PMID- 8359553 TI - Effect of short-term administration of dexamethasone on canine antral gastrin gene expression. AB - The acute effect of corticosteroids on the release and biosynthesis of gastrin still remains unclear. We report the effect of short-term administration of dexamethasone on the antral gastrin gene expression and gastrin levels in 6 dogs, which were treated with dexamethasone (1.5 mg/kg, i.m. daily) for 3 days. One day after treatment, gastrin mRNA levels increased (152 +/- 14%), but serum and tissue gastrin showed no significant changes. With 2 and 3 days of dexamethasone treatment, gastrin mRNA (2 days: 163 +/- 28%, 3 days: 170 +/- 22%), serum gastrin (2 days: from 94 +/- 12 to 168 +/- 23 pg/ml, 3 days: to 180 +/- 16 pg/ml) and tissue gastrin concentration (2 days: from 480 +/- 32 to 664 +/- 31 pg/mg tissue protein, 3 days: to 708 +/- 45 pg/mg tissue protein) significantly increased. However, gastrin mRNA levels were not increased even after 1 day culture of canine antral tissue with dexamethasone in vitro. These findings suggest that short-term administration of corticosteroid may increase the canine gastrin gene expression in vivo by an unknown pathway. PMID- 8359554 TI - Effect of short-term administration of omeprazole on serum gastrin and pepsinogens in antrectomized patients. AB - Omeprazole, a potent and long-acting inhibitor of gastric acid secretion, is known to increase both serum gastrin and pepsinogen A and C levels in unoperated subjects. It has been suggested that the rise in serum pepsinogens is mediated by the omeprazole-induced increase in serum gastrin. This study was undertaken to determine the role of gastrin in hyper-pepsinogenemia induced by antisecretory therapy. We have studied the effect of a 5-day course of 40 mg of omeprazole daily on fasting serum gastrin and pepsinogen A and C levels in 14 patients with an antrectomy and a Billroth I anastomosis (n = 8) or a Billroth II anastomosis (n = 6). In antrectomized patients omeprazole failed to induce any increase in basal serum gastrin. On the other hand, omeprazole increased significantly serum pepsinogen A levels in both Billroth I and II patients, while the rise in serum pepsinogen C level was significant in Billroth I, but just failed to reach statistical significance in Billroth II patients. We conclude that the stimulation of serum pepsinogens A and C by a short-term treatment with omeprazole is not mediated by increases in serum gastrin. This study further shows that omeprazole stimulates gastrin release only from the antrum and not from extra-antral sources. PMID- 8359555 TI - Long-term outcome of acute pancreatitis: a prospective study with 118 patients. AB - 118 patients who had recovered from acute pancreatitis underwent endoscopic retrograde pancreatography (ERCP) during a long-term follow-up (mean 4.4 years, range 1-17) to investigate the frequency and features of residual ductal lesions. Oedematous and necrohaemorrhagic pancreatitis occurred in 35 and in 83 patients, respectively. The aetiology was biliary (39 patients), alcoholic (32), biliary alcoholic (18) and miscellaneous (29). After oedematous pancreatitis, ERCP was normal in 31, showed obstructive pancreatitis in 2 and a slight localized and smooth stricture of the main duct in 2 patients. After necrotizing pancreatitis, 29 patients showed ductal changes without features of chronic pancreatitis, 7 obstructive, 3 chronic calcifying pancreatitis and 44 normal pictures. In 17 patients submitted to two or three ERCPs during a mean 10-year follow-up, the ductal appearance was unchanged in 12, worsened in 3, and improved in 2 patients. The aetiology of pancreatitis and frequency of recurrences was similar in patients with or without scarring lesions. We conclude that residual ductal lesions are common after acute necrotizing pancreatitis. PMID- 8359556 TI - Natural course in chronic pancreatitis. Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease. AB - The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a long-term observation of > 10 years, and severe exocrine/endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths. PMID- 8359557 TI - Role of endothelin and platelet-activating factor in indomethacin-induced gastric mucosal injury in rats. AB - The current study was designed to investigate the role of two potent vasoactive substances, endothelin (ET) and platelet-activating factor (PAF), in the pathogenesis of indomethacin-induced gastric lesions in rats. Treatment with anti ET antibody before indomethacin administration resulted in a significant decline in the total length of the lesions as determined by gross evaluation. In contrast, CV-6209, a specific PAF antagonist, had no effect on the total length of the lesions. The results strongly suggest the incorporation of endogenous ET in the mechanism of gastric damage after indomethacin administration. PMID- 8359558 TI - Congestive gastropathy versus chronic gastritis: a comparison of some pathophysiological aspects. AB - In order to investigate some pathophysiological aspects of the two diseases, 15 patients with congestive gastropathy and 15 with chronic gastritis have been studied and compared with 15 healthy controls. Gastric blood flow as determined during endoscopy by means of laser Doppler flowmetry was found to be significantly increased (p < 0.001) in congestive gastropathy, whereas a significant reduction (p < 0.001) was noted in chronic gastritis. On the other hand, Helicobacter pylori was detected in 80% of cases in chronic gastritis, while the prevalence of the microorganism in congestive gastritis was similar to that in healthy controls. It is concluded that chronic gastritis and congestive gastropathy are related to different pathogenetic factors and require different therapeutic approaches. PMID- 8359559 TI - Luminal release of hyaluronan (hyaluronic acid) in intestinal ischemia in the rat. AB - Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn's disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60 min period of subtotal ischemia without venous stasis (p < 0.05). In sham operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen. PMID- 8359560 TI - Gastric and colorectal cancer in patients attending mission hospitals in rural areas of South-east Asia. AB - 25 missionaries working in Taiwan, Thailand, Indonesia and the Philippines completed questionnaires regarding their clinical practice during the year 1980. Data were collected on the numbers of both gastric and colorectal cancers diagnosed. More than 90,000 out-patients were reviewed, and over 25,000 in patients treated. In total, 76 gastric and 118 colorectal carcinomas were seen. Surgery and radiology were available at 88% of hospitals, but histology at only 53%. In both Indonesia and the Philippines, the relative risk of developing colorectal compared with gastric cancer was 3.3 (95% confidence limits 1.8-6.2 and 1.4-8.5, respectively). In Thailand and Taiwan, these tumours occurred with similar frequencies. Thailand, Indonesia and the Philippines had similar numbers of gastric neoplasms, but Taiwan a significantly higher number than the other countries (z > or = 4.4, p < 0.0001). Thailand had lower numbers of colorectal tumours than the Philippines, (z = 2.2, p < 0.05), Taiwan (z = 3.4, p < 0.001) and Indonesia (p = 5.0, p < 0.0001). Local dietary factors probably play an important role in the development of these tumours. PMID- 8359561 TI - High risk of coeliac disease in Punjabis. Epidemiological study in the south Asian and European populations of Leicestershire. AB - The purpose of this study was to measure the incidence of coeliac disease in different ethnic communities and investigate the hypothesis that the incidence is decreasing in most European countries and the role incomplete retrieval of data may play. In a retrospective study of histologically confirmed cases of coeliac disease between 1975 and 1989 in the City of Leicester, 106 patients with coeliac disease were identified. Of these 86 were European and 20 Asian. The overall incidence of coeliac disease in Europeans was 2.5/10(5)/year (95% CI 2-3.2), in Gujaratis 0.9/10(5)/year (95% CI 0.4-1.8), and in Punjabis 6.9 (95% CI 3.2-12.3). These differences were independent of religious belief. The relative risk to Punjabis compared with Europeans is 2.9 (95% CI 1.5-5.3; chi 2 = 12.5, p < 0.01) and to Gujaratis 8.1 (95% CI 3-22.4; chi 2 = 25; p < 0.001). Gujaratis were at 0.4 risk of Europeans (90% CI 0.2-0.8; chi 2 = 6.7; p < 0.01). The incidence in the urban populations of Leicester was 6/10(5)/year (95% CI 1.3-1.9) which was significantly lower than the 3.2/10(5)/year (95% CI 2.7-3.8; chi 2 = 5.6; p < 0.001) in surrounding rural areas. This study shows that the incidence of coeliac disease in Punjabis (Sikhs, Hindus and Muslims) is 8 times higher than in Gujaratis (Hindus and Muslims) and 4 times higher than in Europeans in Leicester. PMID- 8359562 TI - Epidemiological characteristics of inflammatory bowel disease in Bologna, Italy- incidence and risk factors. AB - Recently, in Bologna, an inflammatory bowel disease incidence of 7.7/10(5)/year has been calculated, about one third of that reported in Northern Europe, confirming the existence of a 'North-South gradient'. A first peak of incidence was observed at 20-29 years of age and a second peak at 60-69 years of age for ulcerative colitis (UC) alone. A prevalence of UC males, mainly after the 7th decade, and of Crohn's disease (CD) females in the first peak was found. A greater frequency of ex-smokers in UC, with a relative risk (RR) significantly higher in males for all age groups (RR = 6.1; p < 0.01) and of smokers in CD with a RR significantly higher in 20- to 29-year-old females (RR = 11.6; p < 0.05) was observed. A different pattern for the two diseases exists: male ex-smokers and young female smokers are at risk of developing UC and CD, respectively. PMID- 8359563 TI - Proceedings Sandostatin, State of the Art. International symposium. Monte Carlo, 1991. PMID- 8359564 TI - Proceedings of the discussion: 'Tolerability and safety of Sandostatin'. PMID- 8359565 TI - Sandostatin therapy of acute oesophageal variceal bleeding. AB - This communication deals with the emergency control of variceal bleeding rather than the prevention of rebleeding. The current main options of oesophageal tamponade, emergency sclerotherapy and drug therapy are discussed, with particular reference to the use of somatostatin. Sandostatin (Sandoz, Basel), a synthetic long-acting somatostatin analogue, was found to reduce transhepatic venous gradient by 30% with no effect on systemic haemodynamics in a study of 16 stable cirrhotic patients. In a trial comparing intravenous infusion of Sandostatin (SMS) to oesophageal tamponade (OT) in active variceal bleeding, 18 of 20 bleeds in the SMS group and 19 of 20 bleeds in the OT group were controlled at 4 h. Ten in the SMS group and 14 in the OT group had no further bleeding during the 48-hour study period. Thus SMS may be useful in the temporary control of active variceal bleeding. PMID- 8359566 TI - Perioperative use of octreotide in gastrointestinal surgery. AB - The evolution of gastrointestinal endocrinology has led to the design and application of analogs of gut peptides to treat disease. Octreotide, a long acting analog of the inhibitory peptide somatostatin, has proven useful in the management of disorders such as carcinoid syndrome and secretory diarrhea due to VIPoma. More recent experience suggests a role for this peptide in the management of certain complications of gastrointestinal surgery. Prophylactic use of octreotide appears warranted in the prevention of carcinoid crisis in selected patients with carcinoid syndrome undergoing invasive procedures, and in the prevention of complications in selected patients undergoing pancreatic surgery. Evidence from placebo-controlled trials supports a role for octreotide in the management of dumping symptoms in severely affected patients, at least in the short term. Octreotide appears to serve a useful adjunctive role in controlling output from postoperative gastrointestinal fistulae and may hasten closure, particularly in pancreatic fistulae. Selected patients with ileostomy diarrhea and short bowel syndrome benefit from octreotide treatment, but the long-term value of the peptide in controlling stool output is less clear. Rare patients with other forms of postoperative secretory diarrhea have been successfully treated with octreotide. Finally, animal and early human experience suggests that octreotide may have a role as an adjunctive treatment of partial small bowel obstruction. In most of these conditions, the available data is sparse and further controlled trials are warranted. PMID- 8359567 TI - Treatment of gastrointestinal fistulas with Sandostatin. AB - Pharmacological treatment of patients with enterocutaneous fistulas aims at reducing output, increasing the chance of spontaneous closure and reducing the time of fistula closure. Our initial experience with octreotide suggests that this drug effectively reduces output of established enterocutaneous fistulas when compared with a placebo in patients on parenteral nutrition. Output reduction was independent of the basal output. Likewise, this somatostatin analogue was shown to accelerate fistula closure in a series of 27 patients treated with the drug after having received parenteral nutrition for a mean of 25 days. When compared with a historical series, the rate of spontaneous fistula closure was not modified by octreotide. PMID- 8359568 TI - Octreotide in dumping and short bowel syndromes. AB - Octreotide inhibits intestinal motility and reduces gastrointestinal secretions. These actions have led to its evaluation in two postsurgical conditions: dumping syndrome and short bowel syndrome. Octreotide substantially reduces symptoms of early and late dumping and prevents the associated phenomena including the increase in packed cell volume considered to be indicative of reduced plasma volume. Its therapeutic benefit probably relates both to slowing of gastric emptying and small bowel transit and inhibition of the release of putative mediators (peptide hormones) of the vasomotor symptoms. Octreotide also reduces intestinal efflux in some patients with the short bowel syndrome. This can lead to a reduction in the volume of intravenous fluid requirements but does not allow an intravenous fluid-dependent patient to change back to an oral regimen. The major mechanism of octreotide's therapeutic effect in this situation may be its ability to reduce endogenous gastric acid secretion. PMID- 8359569 TI - Treatment of pancreatic ascites and external pancreatic fistulas with a long acting somatostatin analogue (Sandostatin). AB - Prior to the advent of somatostatin conservative therapy for pancreatic fistulas, treatment included intravenous nutritional therapy with nothing per mouth and therapeutic agents to diminish pancreatic secretions. None of these modalities were uniformly successful. A prospective study to evaluate the efficacy of a long acting somatostatin analogue (Sandostatin) was carried out. 18 patients-10 with pancreatic ascites and 8 with external pancreatic fistulas-were treated. The ascites resolved in 9 of 10 patients in a mean period of 22 days (+/- 3 days). The external fistulas were all high output fistulas and resolved in 7 of 8 patients. Mean period for closure was 23 days. There were no side effects associated with Sandostatin. Sandostatin has made a major impact on the conservative treatment of pancreatic ascites and is an important adjunct to the management of external pancreatic fistulas. It is emphasised however that surgery may be required for the underlying pancreatic disease. In this regard close surveillance of these patients is necessary. PMID- 8359570 TI - Potential indications for octreotide in gastroenterology: summary of workshop. AB - The potential therapeutic applications of somatostatin and octreotide in gastroenterology involve gut neuro-endocrine tumours, bleeding varices, bleeding peptic ulcers, gastro-intestinal fistulae, pancreatic fistulae, dumping syndrome, pancreatic pseudocysts, short bowel syndrome, acute pancreatitis, AIDS-related diarrhoea, intestinal subacute obstruction, idiopathic 'diarrhoea', irritable bowel syndrome and GIT tumours. Octreotide has a longer duration of action than somatostatin and can be administered by subcutaneous injection, thus making it suitable for long-term administration. Many of the potential gastro-intestinal indications require long-term administration and thus octreotide would be the agent of choice. PMID- 8359571 TI - Somatostatin analogue therapy in functioning neuroendocrine gut tumors. AB - The purpose of the workshop was to critically evaluate the use of octreotide in the management of important surgical and gastroenterological conditions. The topics covered included: (1) management of functioning gut neuroendocrine tumors, (2) new approaches to localize these tumors, (3) the place of octreotide in the treatment of variceal bleedings, and (4) the use of octreotide in postoperative conditions. Octreotide therapy has been shown to be effective in the carcinoid syndrome, in which symptom control is achieved in 85% of patients, and reduction in 5-HIAA in 60%. Although tumor regression is rarely seen, prolongation of survival probably occurs. Control of diarrhea has been achieved in 84% of patients with VIPoma treated with octreotide. Similarly, octreotide has been found to provide effective control of the necrolytic, migratory dermatitis seen in glucagonoma. By contrast, insulinomas are more resistant to somatostatin agonist therapy. In the Zollinger-Ellison syndrome, octreotide is effective in alleviating symptoms and in reducing serum gastrin levels. However, its use in this syndrome has been superceded by omeprazole. Radioiodine-labelled octreotide has been very effective in in vivo imaging of neuroendocrine tumors in the abdomen, and is now considered the best available technique for localizing these tumors preoperatively. Intraoperative localization with a hand-held gamma camera is being developed. There is an exciting future possibility to use the technique to deliver therapy to tumors. Octreotide therapy has been shown to be at least as effective as and without the adverse hemodynamic effects of Pitressin in control of variceal hemorrhage. It should be regarded as one of several modalities of therapy in the condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359572 TI - Gastroenteropancreatic endocrine tumours: effect of Sandostatin on tumour growth. The German Sandostatin Study Group. AB - One hundred and fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumours entered a prospective multicentre trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumours and 5 with other endocrine GEP tumours) to determine the efficacy of 200 micrograms Sandostatin t.i.d. in the control of tumour growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a 'negative' selection of patients included in the trial and suggesting that Sandostatin is unable to prevent disease progression when it is far advanced. In the evaluation of 68 patients followed up for at least 3 months, partial regression was observed in 4.4%, stable disease in 50% and tumour progression in 45%. An initially favourable response occurred frequently, however, it was followed by a decrease in response, from 54.4% at 3 months to 38% at 12 months, for the whole group of patients. Proven inhibition of tumour growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatin exerts a beneficial effect on tumour growth in patients with metastatic endocrine GEP tumours. This beneficial effect decreases with time and is as yet unpredictable in the individual patient. PMID- 8359573 TI - 111In-octreotide scintigraphy in oncology. AB - Various tumors of neuroendocrine origin that have amine precursor and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous injection of the somatostatin analogue [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks in its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1] octreotide) was developed. This analogue is excreted mainly via the kidneys, 90% of the dose being present in the urine 24 h after injection. Using 111In octreotide scintigraphy, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, 3 out of 3 unclassified apudomas, but none out of 18 exocrine pancreatic carcinomas were visualized. Also, 19 out of 19 carcinoids, 15 out of 15 glomus tumors, 8 out of 12 medullary thyroid carcinomas, 6 out of 6 small cell lung carcinomas, 4 out of 4 growth hormone-producing and 6 out of 9 clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD-cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied to visualize breast cancer, lymphomas and granulomas. In 39 out of 50 patients with breast carcinoma, 10 out of 11 patients with non-Hodgkin lymphomas, 3 out of 3 patients with Hodgkin's disease, and 8 out of 8 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359574 TI - Use of radiolabeled somatostatin analogs in the identification and treatment of somatostatin receptor-bearing tumors. AB - Radiolabeled somatostatin analogs are potentially of considerable value in both the localization and treatment of somatostatin receptor-bearing tumors. Whole body 123I-labeled Tyr3-octreotide scintigraphy is capable of detecting and localizing primary tumors and metastatic disease that may not be detectable by other methods. Although it is possible that this technique may be applicable to a wide variety of neoplasms, 123I-Tyr3-octreotide scans appear particularly useful for imaging various gut neuroendocrine tumors, meningiomas, and paragangliomas. This primarily reflects the level of expression of somatostatin receptors by these lesions. In addition to whole body scintigraphy, intraoperative localization by receptor identification utilizing a hand-held gamma detector probe may prove to be an effective means of identifying spread and micrometastasis of somatostatin receptor-bearing tumors. Aside from identification and topographic localization of disease, the detection of an 123I Tyr3-octreotide labeled tumor may be utilized as in vivo assay for the presence of somatostatin receptors. Such observations may prove useful in predicting the susceptibility of an individual tumor to octreotide therapy. Additionally, it may prove possible to deliver a therapeutic dose of radiation to receptor-bearing tumors by the administration of specific radiolabeled somatostatin analogs. PMID- 8359575 TI - Preclinical studies on the anticancer activity of the somatostatin analog octreotide (SMS 201-995). AB - The antiproliferative effect of somatostatin-14 and its analog octreotide on in vitro pancreatic and breast tumor cells has led to the suggestion that octreotide may have further oncological indications in addition to gastroenteropancreatic tumors. To extend these in vitro observations, we evaluated the effect of octreotide in rodent models of pancreatic and breast tumors. Octreotide of 5 or 50 micrograms b.i.d. in nude mice bearing solid MiaPaCa pancreatic tumors (subline 21) or ZR-75-1 breast tumors induced significant inhibition of tumor growth from week 2 until the end of treatment at week 5. After 5 weeks the mean volume of ZR-75-1 tumors in animals treated with the 50-micrograms regimen was 48% that of control. Autoradiographic studies showed a high percentage (71%) of ZR-75-1 tumors to be somatostatin receptor-positive. In addition, the growth of ZR-75-1 cells in vitro was significantly inhibited by octreotide. The drug was also tested in a second breast cancer model, DMBA-induced mammary tumors in rats, and continuous administration of 10 micrograms/kg/h over 6 weeks led to an approximately 50% reduction in the number of tumors arising in the rat mammary gland. These data suggest that pancreatic and breast cancer may be among the malignant diseases clinically susceptible to octreotide. PMID- 8359576 TI - In vivo and in vitro increased pancreatic beta-cell sensitivity to glucose in normal rats submitted to a 48-h hyperglycaemic period. AB - We investigated the importance of the level and the duration of glucose stimulation on the in vivo and in vitro insulin response to glucose in normal rats previously submitted to hyperglycaemia. Rats were made hyperglycaemic by a 48-h glucose infusion. Glucose-induced insulin secretion was investigated in vivo by a 20-min hyperglycaemic clamp and in vitro by the isolated perfused pancreas technique, 3 h after the end of the in vivo glucose infusion. In glucose-infused rats, as compared to controls, in vivo incremental plasma insulin values above baseline integrated over the 20-min hyperglycaemic clamp (delta I) were five times higher during 8 mmol/l glucose clamp, only two times higher in 11 mmol/l glucose clamp and no different in 16.5 mmol/l. Compared to the controls, in vitro incremental plasma insulin concentration above baseline integrated over a 20-min period (delta I) in glucose-infused rats was 16 times higher in response to 2.8 mmol/l glucose, two times higher in response to 5.5 mmol/l, similar in response to 8.3 mmol/l and significantly lower in response to 16.5 mmol/l. In conclusion, our data suggest that a 48-h hyperglycaemic period results in an increased response of the pancreatic beta cell to low glucose. The response is immediately maximal and can not be increased with higher glucose concentrations. This situation could explain the apparent minimal effect of high concentrations on in vitro insulin secretion in previously hyperglycaemic rats and may provide insights into the sequence of events leading to the impairment of beta-cell function in Type 2 (non-insulin-dependent) diabetes mellitus. PMID- 8359577 TI - Osmotically-induced nerve taurine depletion and the compatible osmolyte hypothesis in experimental diabetic neuropathy in the rat. AB - Diabetic neuropathy results from progressive nerve fibre damage with blunted nerve regeneration and repair and may be complicated by nerve hyperexcitability resulting in pain. The naturally occurring amino acid taurine functions as an osmolyte, inhibitory neurotransmitter, and modulator of pain perception. It is also known to have neurotrophic actions. The compatible osmolyte hypothesis proposes that levels of intracellular organic osmolytes including taurine and myo inositol, respond co-ordinately in response to changes in intracellular sorbitol or external osmolality to maintain the intracellular milieu. We hypothesize that glucose-induced sorbitol accumulation in diabetes mellitus will result in taurine depletion in peripheral nerve which may potentially impair nerve regeneration and precipitate neuronal hyperexcitability and pain. This study explored the relationships of taurine, myo-inositol and sorbitol in the rat nerve and their effects on nerve conduction velocity. Osmolyte levels and nerve conduction velocity were determined in sciatic nerve from non-diabetic and streptozotocin induced diabetic rats, with or without dietary taurine or myo-inositol supplementation. Taurine levels decreased by 31% (p < 0.01) and myo-inositol decreased by 37% (p < 0.05) in diabetic nerve as sorbitol accumulated. Taurine supplementation of diabetic animals did not affect nerve conduction velocity but further reduced nerve myo-inositol levels. Prevention of sorbitol accumulation with the aldose reductase inhibitor sorbinil increased nerve taurine levels by 22% (p < 0.05) when compared with untreated diabetic animals. Thus, we have demonstrated an interdependence of organic osmolytes within the nerve. Abnormal accumulation of one osmolyte results in reciprocal depletion of others. Diabetic neuropathy may be an example of maladaptive osmoregulation, nerve damage and instability being aggravated by taurine depletion. PMID- 8359578 TI - Medial arterial calcification in the feet of diabetic patients and matched non diabetic control subjects. AB - The prevalence and distribution of medial arterial calcification was assessed in the feet of four subject groups; 54 neuropathic diabetic patients with previous foot ulceration (U), median age 60.5 (50.5-67 interquartile range) years, duration of diabetes 19.5 (9.9-29.9) years; 40 neuropathic diabetic patients without a foot ulcer history (N), age 68 (62-73) years, duration of diabetes 14.0 (8.0-28.0) years; 43 non-neuropathic diabetic patients (NN), age 60.5 (52-68.5) years, duration of diabetes 14.0 (8.0-28.0) years and 50 non-diabetic control subjects, age 62.5 (53.7-70) years. A single radiologist graded medial arterial calcification as absent, mild or severe, at the ankle, hind-foot, mid-foot, metatarsals and toes on standardised plain lateral and antero-posterior foot radiographs taken by a single radiographer. Diabetes history, vibration perception threshold, ankle systolic pressure and serum creatinine were also assessed. Medial arterial calcification was significantly greater (total score 18 [3-31]) in neuropathic diabetic patients with previous ulceration (U vs N p < 0.01, U vs NN p < 0.001). Non-neuropathic diabetic patients did not have significantly higher arterial calcification scores than age-matched non-diabetic control subjects. Medial arterial calcification correlated with vibration perception threshold (r = 0.35), duration of diabetes (r = 0.32) and serum creatinine (r = 0.41), (all p < 0.01). Logistic regression models showed vibration perception and duration of diabetes to predict the probability of any calcification. Serum creatinine level was added to predict severe calcification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359579 TI - Glucose-induced changes in renal haemodynamics in proteinuric type 1 (insulin dependent) diabetic patients: inhibition by acetylsalicilic acid infusion. AB - The effect of hyperglycaemia on renal function in diabetic nephropathy remains poorly understood. We investigated the renal haemodynamic response to an acute plasma glucose rise from sustained euglycaemia to sustained hyperglycaemia in eight persistently proteinuric Type 1 (insulin-dependent) diabetic patients. Studies were performed in a double-blind cross-over manner after i.v. injection of 450 mg lysine acetylsalicilate (equivalent to 250 mg acetylsalicilic acid) or equal volume of 0.9% NaCl (isotonic saline). In the isotonic saline experiments hyperglycaemia produced a significant rise, by approximately 35%, in glomerular filtration rate in all patients from 41.5 +/- 5.2 to 55 +/- 6 ml.min-1.1.73 m-2 (p < 0.005) and an increase in sodium paraminohippurate clearance from 178 +/- 22.7 to 220 +/- 20.0 ml.min-1.1.73 m-2 (p < 0.05). These changes took place within the first 30 min of glucose infusion and were maintained for a 90 min hyperglycaemic period. Filtration fraction did not change significantly. Infusion of lysine acetylsalicilate lowered baseline glomerular filtration rate (isotonic saline vs lysine acetylsalicilate 41.5 +/- 5.2 vs 30.0 +/- 5.7 ml.min-1.1.73 m-2; p < 0.05) and significantly blunted the rise in glomerular filtration rate during hyperglycaemia (glomerular filtration rate increment: saline vs lysine acetylsalicilate: 13.6 +/- 2.8 vs 5.3 +/- 1.8 ml.min-1.1.73 m-2; p < 0.005). The effects on renal plasma flow were similarly blunted. In five additional patients, time- and volume-controlled isotonic saline experiments during sustained euglycaemia showed no significant changes in glomerular filtration rate and sodium paraminohippurate clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359580 TI - Altered pattern of insulin receptor isotypes in skeletal muscle membranes of type 2 (non-insulin-dependent) diabetic subjects. AB - The human insulin receptor exists in two isoforms (HIR-A alpha-subunit 719 amino acids and HIR-B alpha-subunit 731 amino acids) which are generated by alternative splicing of a small exon and display distinct patterns of tissue-specific expression. Using the polymerase chain reaction we have recently shown that skeletal muscle of non-diabetic individuals contains predominantly mRNA encoding HIR-A while in skeletal muscle derived from subjects with Type 2 (non-insulin dependent) diabetes mellitus similar amounts of each mRNA are expressed. We used a polyclonal antibody which discriminates between HIR-A and HIR-B to assess the isoform expression at the protein level. The antibody showed clearly distinct displacement of insulin binding in skeletal muscle membranes of non-diabetic subjects compared to Type 2 diabetic subjects (displacement of specific 125I insulin binding: 13 non-diabetic subjects 70.0% +/- 14.34, 12 Type 2 diabetic subjects 32.6% +/- 17.45). A control antibody which does not discriminate between both isoforms showed similar displacement of 125I-insulin in membranes of non diabetic and Type 2 diabetic subjects. These data suggest that the altered expression of receptor isotype mRNA in the skeletal muscle of Type 2 diabetic subjects leads to an altered receptor isoform pattern in the plasma membrane. While skeletal muscle membranes of non-diabetic subjects contain predominantly HIR-A, membranes of Type 2 diabetic subjects show an increased level of HIR-B in addition to HIR-A. PMID- 8359581 TI - Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus amongst south Indians. AB - Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA repeat sequences (GCK(3') and GCK(5')) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially matched control subjects. No differences in allele frequencies were apparent at the GCK(5') marker; however, there were significant differences in allele frequencies at the GCK(3') marker between the Type 2 diabetic subjects and control subjects (chi 2 = 11.6, df = 3, p = 0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z + 2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score < -2) at a recombination fraction of zero under five of the ten models used and highly unlikely (-2 < lod score < -1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population. PMID- 8359582 TI - Insulin resistance, hypertension and microalbuminuria in patients with type 2 (non-insulin-dependent) diabetes mellitus. AB - We examined the impact of hypertension and microalbuminuria on insulin sensitivity in patients with Type 2 (non-insulin-dependent) diabetes mellitus using the euglycaemic insulin clamp technique in 52 Type 2 diabetic patients and in 19 healthy control subjects. Twenty-five diabetic patients had hypertension and 19 had microalbuminuria. Hypertension per se was associated with a 27% reduction in the rate of total glucose metabolism and a 40% reduction in the rate of non-oxidative glucose metabolism compared with normotensive Type 2 diabetic patients (both p < 0.001). Glucose metabolism was also impaired in normotensive microalbuminuric patients compared with normotensive normoalbuminuric patients (29.4 +/- 2.2 vs 40.5 +/- 2.8 mumol.kg lean body mass-1.min-1; p = 0.012), primarily due to a reduction in non-oxidative glucose metabolism (12.7 +/- 2.9 vs 21.1 +/- 2.6 mumol.kg lean body mass-1.min-1; p = 0.06). In a factorial ANOVA design, however, only hypertension (p = 0.008) and the combination of hypertension and microalbuminuria (p = 0.030) were significantly associated with the rate of glucose metabolism. The highest triglyceride and lowest HDL cholesterol concentrations were observed in Type 2 diabetic patients with both hypertension and microalbuminuria. Of note, glucose metabolism was indistinguishable from that in control subjects in Type 2 diabetic patients without hypertension and microalbuminuria (40.5 +/- 2.8 vs 44.4 +/- 2.8 mumol.kg lean body mass-1.min-1). We conclude that insulin resistance in Type 2 diabetes is predominantly associated with either hypertension or microalbuminuria or with both. PMID- 8359583 TI - Increased microvascular fluid permeability in young type 1 (insulin-dependent) diabetic patients. AB - Microvascular fluid permeability was assessed by determination of the capillary filtration coefficient in the forearm of ten young Type 1 (insulin-dependent) diabetic patients with a short duration of diabetes, satisfactory glycaemic control and minimal evidence of microangiopathy, and ten age- and sex-matched control subjects. A strain gauge plethysmographic method with a computer based logging and analysis system was used. This enabled differentiation between the volume filling and fluid filtration components of the response to venous pressure elevation. The median capillary filtration coefficient was found to be significantly higher in the young diabetic patients in comparison with control subjects (9.2 x 10(-3) ml.min-1.100 g tissue-1.mmHg-1 vs 3.8 x 10(-3) ml.min 1.100 g tissue-1.mmHg-1, p < 0.001). There were no significant correlations between capillary filtration coefficient and either plasma glucose concentration, haemoglobin A1c or duration of diabetes. As there is no evidence from other studies to support an increase in capillary surface area in the forearms of young Type 1 diabetic patients, these results may reflect a primary change in microvascular fluid permeability. PMID- 8359584 TI - A glucose monitoring system for on line estimation in man of blood glucose concentration using a miniaturized glucose sensor implanted in the subcutaneous tissue and a wearable control unit. AB - We have developed a miniaturized glucose sensor which has been shown previously to function adequately when implanted in the subcutaneous tissue of rats and dogs. Following a glucose load, the sensor output increases, making it possible to calculate a sensitivity coefficient to glucose in vivo, and an extrapolated background current in the absence of glucose. These parameters are used for estimating at any time the apparent subcutaneous glucose concentration from the current. In the previous studies, this calibration was performed a posteriori, on the basis of the retrospective analysis of the changes in blood glucose and in the current generated by the sensor. However, for clinical application of the system, an on line estimation of glucose concentration would be necessary. Thus, this study was undertaken in order to assess the possibility of calibrating the sensor in real time, using a novel calibration procedure and a monitoring unit which was specifically designed for this purpose. This electronic device is able to measure, to filter and to store the current. During an oral glucose challenge, when a stable current is reached, it is possible to feed the unit with two different values of blood glucose and their corresponding times. The unit calculates the in vivo parameters, transforms every single value of current into an estimation of the glucose concentration, and then displays this estimation. In this study, 11 sensors were investigated of which two did not respond to glucose. In the other nine trials, the volunteers were asked to record every 30 s what appeared on the display during the secondary decrease in blood glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359586 TI - Nicotinamide and insulin secretion in normal subjects. AB - Nicotinamide has been given both before and after clinical onset of Type 1 (insulin-dependent) diabetes mellitus in an attempt to prolong beta-cell survival. Nicotinic acid, structurally similar to nicotinamide, induces insulin resistance and increases insulin secretion in healthy individuals. It is not known if nicotinamide has similar effects. Since insulin secretion, as measured by the acute insulin response to intravenous glucose, is used to predict diabetes and to monitor therapy, the effects of nicotinamide must be established before trials in individuals at high risk of progression to Type 1 diabetes can be interpreted. Intravenous tolerance tests were performed according to the ICARUS standard protocol in 10 healthy, adult subjects (age 32 +/- 5.7 years) before and after 14 days of treatment with nicotinamide 25 mg.kg-1.day-1. The acute insulin response after nicotinamide did not differ from the control study, whether measured as the incremental 0-10 min insulin area (278 +/- 142 vs 298 +/- 130 mU.l-1.10 min-1) or as the 1 +/- 3 min insulin level (78 +/- 39 vs 81 +/- 44 mU/l). The late insulin response was equally unaffected, as were basal insulin (5.2 +/- 1.6 vs 5.6 +/- 2.1 mU/l) and glucose (5.0 +/- 0.4 vs 4.9 +/- 0.2 mmol/l) levels and glucose disposal rates (1.98 +/- 0.88 vs 2.04 +/- 0.68%/min). Nicotinamide does not affect insulin secretion and glucose kinetics in normal subjects, confirming its suitability for trials designed to delay or prevent the onset of Type 1 diabetes. PMID- 8359585 TI - The Maillard protein cross-link pentosidine in urine from diabetic patients. AB - The Maillard protein cross-link pentosidine is a fluorescent condensation product of lysine, arginine and ribose. It accumulates in human tissues with age, and the accumulation process is accelerated in the tissues of diabetic patients. Using SP Sephadex C-25 in the pretreatment for HPLC, we examined levels of pentosidine in urine without hydrolysis (free form) and levels of pentosidine in urine after hydrolysis (total forms), from 23 diabetic patients and 21 control subjects. The mean percentages of the values of free form per total forms (+/- SD) were 89 +/- 15% in diabetic patients, 88 +/- 16% in control subjects and 89 +/- 15% in total populations of diabetic patients and control subjects. There was a significant correlation between the values of free form and total forms in diabetic patients (r = 0.983, p = 0.0001), in control subjects (r = 0.820, p < 0.02) and in total populations of diabetic patients and control subjects (r = 0.951, p = 0.0001). The mean level of pentosidine per mol creatinine (+/- SD) was significantly elevated in urine from diabetic patients as compared to the level in control subjects (8.8 +/- 4.3 mumol/mol creatinine vs 4.2 +/- 1.4 mumol/mol creatinine, p = 0.0001 in free form; 10.1 +/- 5.3 mumol/mol creatinine vs 4.7 +/- 1.4 mumol/mol creatinine, p = 0.0001 in total forms). These results demonstrate that urinary pentosidine, especially in free form, could be a useful marker for the assessment of diabetes and diabetic complications. PMID- 8359587 TI - The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with type 1 (insulin dependent) diabetes mellitus. AB - Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s.c. dose of recombinant insulin-like growth factor I (40 micrograms/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1 +/- 28.2 ng/ml, mean +/- SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; p = 0.01), as were the insulin requirements for euglycaemia (0.25 +/- 0.02 compared with 0.31 +/- 0.04 mU.kg-1.min-1; p = 0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9 +/ 2.7 compared with 67.9 +/- 16.0 mU/l; p = 0.001) but no significant differences in ketone or lactate levels were detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359588 TI - Early insulitis and the islet vascular system. PMID- 8359589 TI - Follow-up of anti-beta-lactoglobulin antibodies in children with type 1 (insulin dependent) diabetes mellitus. PMID- 8359590 TI - Persisting antibodies to glutamic acid decarboxylase in type 1 (insulin dependent) diabetes mellitus are not associated with neuropathy. PMID- 8359591 TI - Characterization and expression analysis of the murine rck gene: a protein kinase with a potential function in sensory cells. AB - We have characterized a murine protein kinase gene, rck, which was identified by crosshybridization with sequences from the v-ros tyrosine kinase gene under conditions of reduced stringency. cDNA analysis indicated that rck encodes a putative protein kinase related to the cdc2 subclass of the gene family and that the gene is identical to mak identified previously in the rat. An extensive expression analysis in the mouse performed by a combination of in situ hybridization and RNase protection revealed a novel and restricted pattern of expression: rck transcripts are found in two cell types involved in sensory transduction, photoreceptors and olfactory receptors as well as in epithelia of the respiratory tract and choroid plexus. Specific transcripts are also found in pre- and postmeiotic male germ cells. We suggest therefore that rck participates in signalling pathways important in a distinct set of cells, remarkably among them cells involved in sensory signal transduction. PMID- 8359592 TI - 'Spontaneous' transformation as aberrant epigenesis. AB - The NIH 3T3 line of cells has particular advantages for studying the dynamics of change in cellular phenotype in response to environmental conditions. Similar to stem cell growth during development, the cell line changes its phenotype under growth constraints that elicit differentiation or, alternatively, it maintains its original state over many replication cycles when grown without constraint. Unlike many cell types which respond by undergoing terminal differentiation, the NIH 3T3 cells continue to multiply indefinitely following an induced alteration in phenotype; the heritability of this change may thus be analyzed under stringent conditions of cell culture. During the course of over two years of frequent passage at low density in high calf serum (CS) concentration, a new subline developed which exhibited a consistent capacity to respond quickly and pervasively to growth constraints with an increase in saturation density, development of transformed foci in confluent cultures and altered appearance of isolated colonies. A retrospective study was undertaken, with cells from cryopreserved samples, of the course of changes in responsiveness of the cells to growth constraint leading up to the highly responsive state. Three stages were discerned, the first with an initially high capacity of a small fraction of cells to produce diffuse foci, but with a rapid decline in this capacity with frequent low density passages; the second stage, extending over more than 200 passages, of refractoriness to transformation; and the third stage (which probably arose by mutation) in which there is a consistent transformation-related response by the entire population to growth constraint, a response which has remained relatively constant over some 100 passages. A striking and novel feature of the third stage is seen on cloning the cells. Almost all the colonies obtained by cloning cells from post-confluent, growth-inhibited cultures are distinctly different in morphology from those obtained by cloning cells from the frequent low density passages. The pervasiveness of this morphological change among the clones is unmistakable evidence for a heritable adaptive response to growth constraint by most if not all of the cells in the population. The population-wide response of the cells of the third stage offers the opportunity for a rigorous, quantitative analysis of the nature of this type of persistent cellular change. Although cells of the third stage may be of mutational origin, their pervasive heritable response once the variant population is established supports the concept of progressive state selection which postulates that transformation can arise by the continuous fluctuation of growth states within cells, accompanied by the progressive selection of those states best suited to function under the selecting constraint. Relevance of the concept to the process of differentiation under growth constraint is considered. PMID- 8359593 TI - NGF retards apoptosis in chick embryo bursal cell in vitro. AB - Recent studies have demonstrated that the action of nerve growth factor (NGF) is not restricted to neuronal cells but also affects cells of the immune system. In a previous work on the effect of NGF on the chick embryo bursa of Fabricius both in vivo and in vitro, we observed that NGF prolongs bursal cell survival in vitro. In the present study we report that the increase of viable cells in NGF treated cultures is not due to a proliferative effect of NGF on bursal cells but to a reduction of cell mortality. The morphological analysis revealed that bursal cells in cultures die by apoptosis, which was also shown by the typical pattern of DNA fragmentation, a hallmark of this cell death process. It is concluded that NGF, with an action similar to that described in sympathetic neurons and PC12, could retard bursal cell death by influencing apoptosis. PMID- 8359594 TI - Expression from the proximal promoter of the carbonic anhydrase 1 gene as a marker for differentiation in colon epithelia. AB - Carbonic anhydrase 1 (CA1) catalyses the reversible hydration of CO2 and is important for cellular diffusion of CO2, ion transport and pH regulation. The gene encoding CA1 (CA1) has two promoters. In adult colon epithelia the proximal promoter determines high levels of expression and the distal erythroid promoter is repressed. RNA in situ hybridisation shows that CA1 mRNA is abundant in differentiating cells of the colonic crypt as they migrate to the luminal surface, but is not present at the base of the crypts and levels are low on the luminal surface. It is likely that CA1 gene expression in these cells is regulated by differential transcription and/or mRNA stability. In contrast CA1 protein is localised predominantly on the luminal surface. Since CA1 mRNA and protein do not exactly co-localise it can be inferred that CA1 expression is also subject to post-transcriptional control. CA1 mRNA is significantly reduced in colon carcinoma and in adenomas from familial adenomatous polyposis patients. Loss of CA1 expression is associated with the disappearance of differentiated epithelial cells. Out of twelve colon carcinoma cell lines three, LIM1215, LIM1899 and HT115, expressed CA1 and nine did not. This variation in expression may also be associated with cell type differentiation. PMID- 8359596 TI - The editorial business. PMID- 8359597 TI - Electronic publishing. PMID- 8359595 TI - The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. AB - The differentiation of the predominant cell types of the mucosal epithelium of the mammalian gastrointestinal tract is characterized by increasing amounts of an intermediate-sized filament (IF) protein designated cytokeratin (CK) 20 which is a major cellular protein of mature enterocytes and goblet cells. Here we report the isolation of the human gene encoding CK 20, its complete nucleotide sequence and the amino acid sequence deduced therefrom that identifies this polypeptide (mol. wt. 48553) as a member of the type I-CK subfamily. Remarkable, however, is the comparably great sequence divergence of CK 20 from all other known type I CKs, with only 58% identical amino acids in the conserved alpha-helical 'rod' domain of CK 20 and, e.g. CK 14. Using riboprobes corresponding to exon 6 of the gene in Northern blot and ribonuclease protection assays, we show that the approximately 1.75 kb mRNA encoding CK 20 is specifically produced in cells of the intestinal and gastric mucosa, including tumors and cell lines derived therefrom. The appearance of CK 20-positive cells in human embryonic and fetal development and in adult tissues has been studied using immunohistochemistry with CK 20-specific antibodies. CK 20 synthesis has first been recognized at embryonic week 8 in individual 'converted' simple epithelial cells of the developing intestinal mucosa. In later fetal stages, CK 20 synthesis extends over most goblet cells and a variable number of villus enterocytes. The distribution of CK 20-positive cells in the developing gastric and intestinal mucosa is similar to- but not identical with--the pattern in the adult intestine in which all enterocytes and goblet cells as well as certain 'low-differentiated' columnar cells contain CK 20, whereas the neuroendocrine ('enterochromaffin') and Paneth cells are negative. In gastrointestinal carcinomas similarly examined, CK 20 has been detected in almost all cases (50/52) of colorectal adenocarcinomas, including all grades of differentiation and malignancy and also metastatic tumors, whereas CK 20 immunostaining in gastric carcinomas has been found less consistent and more heterogeneous. The possible biological meaning of the specific expression of the CK 20 gene in certain cells of the gastrointestinal tract and carcinomas derived therefrom and the regulatory mechanisms involved in the integration of the protein in the IF cytoskeleton are discussed. PMID- 8359598 TI - A study of the referral decision in general practice. AB - The applicability of published models of the referral decision in general practice was investigated by asking general practitioners (GPs) to record data on consultations during which referral to a consultant's outpatient clinic was considered, whether this resulted in referral or not. The GPs were then interviewed about their decisions with particular reference to patient factors, clinical factors, their perception of the risk involved, consultant factors and time factors. The doctors varied in the weight that they gave to the patient's wishes, and also in their selection and interpretation of diagnostic data. Risk to the patient was rarely a major consideration; neither was risk to the doctor's self-esteem. There was virtually no evidence of conflict arising during the decision-making process, and doctors on the whole, did not feel pressed for time. This was, however, a self-selected sample of highly motivated general practitioners. It is suggested that the assumptions on which the conflict model of decision-making is based do not apply to the majority of referral decisions in general practice. PMID- 8359599 TI - Non-attendance at outpatient clinics: is it related to the referral process? AB - Non-attendance at outpatient clinics is a complex problem and previous studies have concentrated on hospital-related factors. It has been suggested that non attendance might be related to the referral process, including the selection of patients for referral and the quality of communication between GP and patient. These issues are examined in a study of 1492 patients given first-time appointments at ENT and gastroenterology clinics. Non-attendance rates were 26 and 20% respectively. Non-attendance was not related to the nature, severity or duration of the patients' presenting problems at the time of referral or to their perception of the need for referral. Resolution of symptoms did not appear to be a major reason for non-attendance. Patients were significantly less likely to attend if they had been unable or only partly able to discuss their health problem with their general practitioner. Those who had requested referral were equally likely to default. PMID- 8359600 TI - The influence of a desk-top analyser on the number of laboratory tests used in daily general practice. A randomized controlled trial. AB - This study evaluated the influence of a desk-top analyser, used in general practice, on the mean number of blood tests per contact, prescribed or analysed by general practitioners. A randomized controlled trial was used. The mean number of blood tests per contact requested by two groups of GPs, before and after the introduction of a Reflotron in the intervention group was compared. Practitioners were assigned to the control group or to the intervention group by stratified randomization. Flemish GPs, known by the Flemish Institute of General Practice as interested in research were enrolled into the study. There were two registration periods of 8 weeks each. The weekly number of doctor-patient contacts and all requested or performed blood tests for each patient were registered. During the second period the members of the intervention group were asked to use the Reflotron, following their own judgement, and to register the total number of tests per contact, performed with it, on a special form. In the Reflotron group there was a slight increase in the median of the relative differences between the intervention and the base-line period (3%). In the control group the median of the relative differences decreased (-7%). The difference between both groups was not statistically significant (P = 0.17). In both groups the size and direction of the relative differences of the individual practices were very different. No statistically significant differences were found in any of the subgroups. PMID- 8359601 TI - Dry chemistry instruments in primary care. I. Operating conditions and financial considerations. AB - The objectives of this study were to describe the operating conditions of dry chemistry instruments in primary care, as well as to elucidate financial aspects in general practice fee-for-service settings. We used questionnaires mailed to all users of the two most used dry chemistry instruments in Norway, as well as to a 14% random sample of Norwegian GPs. The overall response rate was 79%. The mean number of dry chemistry analyses varied considerably between individual users, but in general a substantial number of analyses were carried out. Even though most analyses on the instruments' repertoire were available in all user groups, a total of 13 additional constituents were suggested to be included in the repertoire. In occupational health care most results were ready when the client was present; this was not the case in general practice. The instruments were more profitable when more constituents were analysed per sample, although profitability varied substantially in the period studied (1986-1989). A discrete time history event analysis revealed that net profit earned, lower instrument price, available information about the technology and being in solo practice significantly influenced the decision to buy an instrument in fee-for-service practices. PMID- 8359602 TI - Dry chemistry instruments in primary care. II. Comparison of users with non users. AB - One way of studying the impact of dry chemistry desk-top instruments in primary care is by comparing users and non-users of this technology with respect to practice setting and changes in everyday practice, as well as to elucidate reasons for not implementing this technology. We therefore mailed a similar questionnaire to all users of the most-used dry chemistry instruments in Norway (n = 298) and to a 14% random sample of general practitioners (n = 381), and a 40% random sample of doctors in occupational health care units (n = 181). The response rate was 77-79% and 200 users and 281 non-users could be included. In general practice, more users were solo practitioners and more users had a cell counter in the office laboratory; fewer occupational health care users kept computerized records. Users reported improvement in diagnosis and treatment and claimed that patient satisfaction had improved. In general, an increase in the number of tests was estimated. Non-users were more pessimistic with regard to improvements in office laboratory service, and stated perceived problems regarding cost, workload and analytical quality as well as good service from the hospital laboratory as reasons for not implementing such instruments in their practice. PMID- 8359603 TI - Coronary heart disease prevention: the role of the general practitioner. AB - The objectives of the study were to identify the level of general practitioner (GP) involvement in activities aimed at coronary heart disease prevention and to explain variations in involvement. These questions were explored through a postal survey of a random sample (n = 1696) of GPs in England of whom 64% completed questionnaires. Ninety-four per cent of GPs reported that they were involved in risk factor assessment in the consultation although these assessments most commonly involved blood pressure testing and identification of smoking. Ninety one per cent of practices were reported by the GP to have a lifestyle risk assessment clinic where there was more evidence of systematic risk assessment. These clinics were usually run by a practice nurse as were lifestyle risk factor management clinics although GPs were more involved in hypertension and cholesterol clinics. Positive attitudes to prevention and training in health promotion were associated with higher GP involvement, and higher practice involvement was associated primarily with the number of practice nurses employed. The implication of these findings are discussed. PMID- 8359604 TI - Socio-economic factors, health care consumption and rating of abdominal symptom severity. A report from the abdominal symptom study. AB - A study of the abdominal/gastrointestinal symptom panorama in relation to socio economic factors and health care consumption in the general population was performed in Osthammar, Sweden. A postal questionnaire was sent to a representative sample of the adult population (n = 1260). The response rate was 87%. The responders with symptoms (52.1%) subjectively rated their illness on visual analogue scales. All responders were classified as asymptomatic or having 'minor' or 'major' abdominal symptoms. Those having dyspepsia, reflux or irritable bowel syndrome were also ranked as 'minors' or 'majors'. The proportion of subjects with abdominal/gastrointestinal complaints decreased with age, mainly due to a decrease of 'major' symptoms. Also, the proportion of complainers increased among the more educated. Those on sick leave and students had more and worse symptoms than the others, despite the former seldom stating abdominal discomfort as the main reason for sick listing. Fifty-five per cent of all persons reporting abdominal/gastrointestinal symptoms had at some time consulted a doctor because of such complaints, the proportion increasing with severity, as did drug consumption and the rate of previous abdominal operations, with appendectomy as an exception. The results show that it is possible to rank the illness along a severity dimension among persons with abdominal/gastrointestinal complaints in epidemiological research. PMID- 8359605 TI - Family practice in Cuba: evolution into the 1990s. AB - A group of practising physicians, family practice academicians and medical students visited Cuba in 1991. The purpose of this visit was to assess the current status of the discipline of family medicine in the country. Numerous interviews were conducted with practising family physicians, Cuban medical physicians in other medical specialties, the medical school faculty, patients and officials from the Ministry of Public Health. A summary of the content of these interviews constitutes the following paper. The authors conclude that the Cubans have developed a medical care system that has its basis in family practice, and provides a model which could be emulated not only in less developed, but also in more developed countries. PMID- 8359607 TI - Implementation of the national cervical cancer screening in general practice and feasibility of a general practice-based call system: the GP's opinion. AB - Thus far, the response to the nationwide screening programme for cervical cancer in The Netherlands, which was started in 1989, has been disappointing. One way to improve response is to involve general practitioners in the call system. A postal survey was conducted to review the implementation of the current screening programme in general practice and to examine the willingness of general practitioners to participate in a general practice-based call system. The response rate to the survey was 90%. The general practitioners were dissatisfied with follow-up, cost and time spent and compliance of women. Of all respondents 60% had already set up a call system within the practice or were willing to do so; another 31% were willing to participate in a regionally organized practice based call system. On the basis of the results of this study a centralized general practice-based call system is recommended. The next step is to study the applicability of this system in a pilot programme. PMID- 8359606 TI - Diabetes and its long-term complications in general practice: a survey in a well defined population. AB - The aim of this study was to assess the prevalence of long-term complications in all patients with non-insulin-dependent diabetes mellitus, who were known to their general practitioners (GPs). During one year 19 GPs in the area of Hoogeveen in the Netherlands examined their non-insulin-dependent (NIDDM) patients, including those under specialist's care. A detailed protocol was used; the GPs were trained in the diagnostic procedures. Complications were either already known from the records or newly discovered during screening. In a population of 41,940 14.5/1000 patients with diabetes were identified: 12/1000 NIDDM and 2.5/1000 insulin-dependent diabetes mellitus (IDDM). Of the 509 NIDDM patients, 387 (76%) could be screened for late complications. Signs and symptoms of late complications were found in many patients: retinopathy (14%), nephropathy (57%), neuropathy (68%) and macroangiopathy (53%). The prevalence of serious complications was: proliferative retino- and maculopathy (3.3%); diabetic foot (2.6%); renal failure (2.5%). The systemic screening revealed a high number of previously unknown cases. It is concluded that many patients with NIDDM develop signs and symptoms of late complications. Most cases are identified by systemic screening only. More long-term studies of the prognosis of late complications in NIDDM are needed. PMID- 8359608 TI - SFAT-AM: short family therapy in ambulatory medicine. Treatment approach in 10-15 minute encounters. AB - The question of the possibilities latent within an appointment lasting on average only 10-15 minutes, under the pressures of a heavy workload in a public clinic, has occupied the authors for three years. SFAT-AM: Short Family Therapy in Ambulatory Medicine, has been developed with aim of offering solutions to this question. The theoretical background is taken from family medicine with a biopsychosocial (b.p.s.) systems approach. The authors formulated series of basic doctor-patient encounters which last on average 10-15 minutes. The basic encounter is a kind of didactic checklist model which presents to the doctor possibilities latent within. Emphasis is placed on the art of treatment and the meeting itself as therapeutic. During the meeting, patient's satisfaction, psychosocial information and the doctor's inner voice help the participants adjust to each other and move from stage to stage. The approach also relates to the possibility of joint work together with colleagues or with members of different teams in the clinic. The doctor makes use of communication techniques and reaches a b.p.s. diagnosis which will be the basis for suggesting a treatment. The presented model was tried by the authors and by trainees as part of a specialization course in family medicine. The trainees received between 20 and 70 academic hours of instruction. From the doctors' report it can be seen that SFAT-AM can be used in a primary clinic. Future research should give more specific answers to questions about the model's desirability, cost-efficiency, and job satisfaction. (Doctors will be referred to in the male gender throughout the article). PMID- 8359609 TI - Stories from the sealed rooms: patient interviews during the Gulf war. AB - The mass deployment of gas masks to an entire population, which occurred in Israel prior to the Persian Gulf crisis and their use in early 1991, were phenomena without precedent. In addition to the historical significance, there were considerable health and psychological ramifications. This research examines the experiences of the Israeli public during the Gulf war using a qualitative methodological approach, narrative analysis. Interviews of a convenience sample of 60 patients attending primary care clinics were audio-recorded by three family physicians using an open-ended interview guide. Encounters took place at sites located in the north, south and centre of the country during the period of Iraqi missile attacks. Patients' stories were analysed using a multistep narrative analysis protocol. Seventy per cent of subjects reported deleterious health effects related to the missile attacks or civil defence measures, mainly psychological and neurological complaints, sleep disorders, gastrointestinal and respiratory symptoms. Recurrent themes and metaphors in the narratives most often focused on the difference of this war to others, the central involvement of the family, concern for children and identification and connection to the nation. The Scud missile attacks combined with the civil defence measures had significant impact on the population, as manifested in subjects' stories, symptoms, symbols and behaviour. Narrative analysis provided an efficient method to capture the rich texture of patients' experiences. PMID- 8359610 TI - Why do mothers consult when their children cough? AB - Mothers' beliefs and evaluations of their child's illness were studied in a group of 30 mothers who had consulted a general practitioner because of a cough. Data were collected by tape-recorded semi-structured interviews conducted in their own homes. A major concern for mothers was their fear that their child was going to die, usually because of choking on phlegm or vomit, but also through an asthma attack or cot death. Mothers were also worried that their child would develop long-term chest damage. Particularly important in mothers' assessments were their experience of disturbed sleep because of worries about their child dying at night and their belief that the cough was 'on the chest' which gave rise to worries about dying through choking on phlegm and long-term chest damage. Antibiotics were commonly believed to be required to break up phlegm which might cause the long-term damage or the choking and death. PMID- 8359611 TI - The patient's family history: a key to the physician's understanding of patients' fears. AB - Patients often feel considerably worried by conditions that appear to be biomedically mild to their physicians. Their reaction may be linked to personal experience from cases of severe disease in their family history. In this qualitative study, 30 primary health care patients were interviewed about their definition of their present problem, their fears and associations with their family history. For several patients, the discrepancy between objective signs and fears was linked to cases in their family. Death or threats to life, especially when occurring prematurely, appeared to be significant. The same was true for actual or threatening disability in family members. A condition perceived to have been overlooked also seemed to be important for some patients. These findings may be used to understand patients' rationale for seeking care. The subject should be the theme for further investigation. PMID- 8359612 TI - Shared understanding of the qualitative research process. Guidelines for the medical researcher. AB - The qualitative research process is presented and discussed as a model, emphasizing matters frequently experienced as unfamiliar by the medical researcher. This model represents a prescriptive methodology, implying underlying values on construction of scientific knowledge where shared understanding- intersubjectivity--is considered as essential. Various stages of the research process are demonstrated, drawing attention to matters that influence analysis and the paths to knowledge, especially preconceptions and theoretical frames of reference. Principles and procedures related to analysis of qualitative data, as decontextualizing and recontextualizing, are explained. The structure of this model, accentuating the researcher's responsibility to give access to all levels of the research process, underlies all kinds of scientific inquiry. Such principles should probably more often be explicitly questioned and accounted for in all sorts of medical research. PMID- 8359613 TI - Factors affecting general practitioners' recruitment of patients into a prospective study. AB - Many research projects depend on general practitioners (GPs) to recruit patients into the study. As part of a study of patients' experiences of treatment for menorrhagia, completeness of recruitment and the extent of bias introduced by failure to recruit was assessed. Only 129 (41%) of 315 GPs who had agreed to recruit patients actually did so. A review of notes in six practices revealed that only 40 (20.4%) of 196 eligible patients had been recruited. There was some evidence that the recruited patients had more severe symptoms than those not recruited. There was no difference in recruitment rates between male and female doctors, but those who had received a practice visit from a member of the research team recruited more patients. A survey of participating GPs revealed that forgetfulness and time pressures were the main factors inhibiting recruitment. PMID- 8359614 TI - Measuring functional status in a population survey. The Dartmouth COOP functional health assessment charts/WONCA used in an epidemiological study. AB - In a population study, a random sample of 398 persons from 20 to 72 years answered the six item version of the Dartmouth COOP functional health assessment charts/WONCA. The results according to age and sex are presented. The charts have been developed primarily for use in clinical settings. In a cross-sectional study in a normal population, the instrument seems feasible in use and it differentiates between the sexes and age groups. PMID- 8359615 TI - Influencing diagnostic and preventive performance in ambulatory care by feedback and reminders. A review. AB - The number of good quality studies on the effect of feedback and reminders on diagnostic and preventive activities in ambulant practice is still low. The interventions and procedures studied differ widely, and the reporting of the results is insufficiently precise. This makes comparison difficult and quantitative pooling impossible. Nevertheless, the literature supports the contention that feedback reduces the use of diagnostic tests and the costs thereby engendered. It also discloses a positive effect of feedback on the adherence of medical practice to guidelines or standards. In this respect, the effect of reminders seems to exceed that of classical methods of feedback. There is still a need for research on the effect of feedback, reminders and other instruments for quality assurance on various aspects of medical performance in different settings. PMID- 8359616 TI - Conference report: teaching old docs new tricks: research dissemination and professional behavioural change. PMID- 8359617 TI - Selections from current literature: psychiatric disorders in primary care. AB - Although each paper reviewed for this article examined different populations, used differing measures to detect psychiatric problems and differing criteria to diagnose psychiatric illness, the results consistently demonstrate the high prevalence of psychiatric illness in the community and in primary care. Twenty five per cent of all attenders, 52% of high utilizers and 46% of illness initiation visits in primary care have a diagnosable psychiatric illness. Depression and anxiety appear to be the most frequently encountered psychiatric problems in primary care patients. Also consistent in the three primary care based reports is the finding that primary care physicians under-diagnose psychiatric illness in their patients. Reasons for this appear to include: (i) the relatively short duration of primary care visits (though against this is the frequency of visits-particularly among high utilizers), (ii) the presentation of somatic symptomatology by patients, (iii) the shortcomings of current diagnostic categories when applied to primary care patients, (iv) the frequency of relatively mild and subthreshold conditions in primary care patients, and (v) the lack of evidence demonstrating beneficial treatment outcomes for primary care psychiatric disorders and the related difficulty of extrapolating treatment results from hospital and referral based trails to primary care patients. Despite these difficulties, family physicians need to be watchful to detect psychiatric illnesses in those patients most likely to benefit from treatment. The finding of Broadhead et al. indicating that persons with symptoms of depressed mood are at increased risk for development of major depression over the subsequent 12 months is of interest to family physicians. More frequent follow-up of this group may be indicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359618 TI - Alpha-interferon 2b in the treatment of chronic hepatitis C: interim report of the first multicentre Australian trial. AB - Interferon has been shown to be effective in the treatment of chronic hepatitis C but the optimal treatment regime has not yet been defined. Studies using 3 million units (MU) of interferon thrice weekly (tiw) for 6 months have shown normalization of serum alanine aminotransferase (ALT) in about 50% of patients, but relapse occurs in at least 50% of responders after interferon is stopped. The aims of this study were to determine whether 5 MU of interferon tiw produces a higher response rate than 3 MU tiw and to examine if the higher dose results in more sustained remissions. In addition, factors that are associated with a more or less favourable response to interferon treatment were sought. Overall, 65% of patients responded and no advantage of the higher dose therapy was found, either in terms of response or relapse rate after treatment. The presence of cirrhosis on the pre-treatment liver biopsy was associated with a poor response rate to interferon and a trend towards a higher relapse rate. Risk factor for acquisition of disease was also related to likelihood of response but not relapse. We conclude that two thirds of Australian patients with chronic hepatitis C initially respond to interferon treatment. Positive predictors of response are intravenous drug use as a risk factor and histologically less severe liver disease. Relapse occurs in two thirds of all responders. PMID- 8359619 TI - Long-term therapeutic efficacy of interferon for patients with chronic hepatitis C. AB - Interferon is being used for therapy of chronic hepatitis C, but its long-term results have not been reported. We studied 65 patients with this disease who were monitored for at least 2 years after completion of the therapy. Almost all patients who had responded to therapy at 6 months after the end of therapy had normal levels of alanine aminotransferase (ALT) when evaluated later. The level of ALT became normal for the first time in some patients more than 6 months after therapy ended. The level of ALT in many of the patients without HCV RNA had become normal 6 months after the end of the therapy. One of three schedules was employed: three times weekly long-term; daily for two weeks and none for two weeks in a cycle; and daily for several weeks; 57%, 29%, and 17% of the patients on these schedules came to have normal ALT levels. Patients without HCV RNA at six months after completion of therapy tended to have higher responses in terms an increased level of 2',5'-oligoadenylate synthetase of mononuclear cells in vitro before therapy began. However, therapy three times per week was effective even for some patients judged not responsive to IFN by this test. The results showed that IFN therapy was effective for chronic hepatitis C when judged by long term results. PMID- 8359620 TI - Autoimmunity during alpha-interferon therapy for chronic hepatitis C. AB - One hundred twenty-five patients with chronic hepatitis C were treated with natural IFN alpha or recombinant IFN alpha-2a, daily doses of 3 MU or 9 MU, respectively. IFNs were given 6 times a week for the first 2 weeks followed by thrice weekly administration for 12 weeks or more. ANA, TMA, AMA and anti-DNA antibody newly developed in 8, 1, 2 and 1 patient, respectively. Furthermore, we encountered some cases in which underlying autoimmune disorders were thought to be exacerbated by IFNs. It is important to pay sufficient attention to the development of autoimmune diseases in IFN therapy for chronic hepatitis C. PMID- 8359621 TI - PGE2 protects isolated cells against injury through multiple mechanisms. AB - In order to clarify how PGE2 regulates gastric mucosal integrity, we examined the effects of PGE2 on ethanol-caused injury of isolated gastric chief cells, cultured gastric mucous cells from guinea pigs and Balb/c 3T3 fibroblasts. Pretreatment of these cells with PGE2 reduced ethanol-caused injury of the cells. Furthermore, pretreatment of gastric mucous cells with indomethacin enhanced ethanol-caused injury, suggesting that endogenous PGE2 may be involved in the cell protection. PGE2 stimulated an increase in diacylglycerol (DG) accumulation in chief cells and treatment of chief cells with synthetic DG reduced the injury of the cells. However, DG accumulation was not observed in gastric mucous cells treated with PGE2. Therefore PGE2 may protect the cells from injury through a variety of mechanisms. In addition, PGE2 enhanced the survival of the quiescent fibroblasts cultured in the absence of serum, while PGE2 had no survival enhancing effect on gastric mucous cells. These results suggest that the mechanism by which PGE2 preserves the cell viability may depend on not only cell types used but also how the cells are injured. PMID- 8359623 TI - Alteration of gastric microcirculation in ulcer healing and recurrence: significance of autonomic nervous regeneration and mesenchymal cell. PMID- 8359622 TI - Prospect of the treatment of human gastric ulcers with orally administered epidermal growth factor. PMID- 8359624 TI - Epidemiology and genetics of peptic ulcer. AB - At the turn of the century, duodenal ulcer rose from rarity to affect 10% of males in their life time, subsequently declining in some countries such as UK, levelling off in others such as Germany, and continuing to increase in still others such as Hong Kong. The annual incidence per 1000 population varies from about 1 in Japan to 1.5 in Norway, 1.8 in USA and 2.7 in Scotland, and the frequency also varies within many individual countries, such as Australia, China and India, and among races such as a higher prevalence among whites than blacks in USA and among Chinese than Javanese in Indonesia. Ulcer frequency is higher in winter months, and this appears universal, being true in cold as well as in warm countries. Most places report a rise of ulcer rates among the elderly in recent decades. The male to female ratio also varies geographically, for example from 1:1 in USA to 18:1 in India, and with time such as moving from 2:1 to 1:1 in the last two decades in USA, and the duodenal ulcer to gastric ulcer ratio varies widely from place to place, for example from 0.8 in Japan to 19:1 in Africa and 32:1 in India. Placebo healing rates also differ geographically, ranging from 5% in Philippines to 78% in Mexico. These epidemiological data can only be explained by the presence of multiple aetiological factors, including analgesics, society stress, cigarette smoking, Helicobacter pylori, dietary factors, and genetic factors. Three lines of evidence support a genetic role: family studies, twin studies and blood group studies. Family aggregation occurs more commonly in patients with early-onset (< 30 yr) of symptoms. Blood group O prevalence is more associated with late-onset of symptoms. Other genetic markers include nonsecretor status, HLA antigens, phenylthiocarbamide taste sensitivity, and alpha-1 antitrypsin. Genetic syndromes such as MEN I also support a genetic role and give insight into pathogenetic mechanisms. The best physiological marker is still hyperpepsinogenemia I, which is transmitted by autosomal dominance, despite recent report of lower serum pepsinogen 1 after healing of Helicobacter pylori associated gastritis. PMID- 8359625 TI - The role of Helicobacter pylori in peptic ulcer disease. AB - The linking of relapse of duodenal as well as gastric ulcers with Helicobacter pylori (H. pylori) has been a considerable advance in managing patients with peptic ulcer disease. However, pathogenetic role of H. pylori in peptic ulcer still remains unclear. The aim of this study was to assess the relationship between H. pylori infection and inflammatory cell infiltration in gastric mucosa in peptic ulcer disease. Sixty-four patients with endoscopically proven gastric ulcer and 26 patients with duodenal ulcer were evaluated by prospective study. Biopsy specimens were taken from the ulcer margin, corpus and antrum. Eradication of H. pylori was attempted by concomitant administration of amoxycillin 500 mg, metronidazole 250 mg and bismuth subnitrate 1 g twice daily for 2 weeks. H. pylori positive rates in clinical stages of gastric and duodenal ulcer showed almost the same values of more than 90%. The prevalence of H. pylori at the antrum and corpus was almost the same as that between gastric and duodenal ulcer patients, whereas a dramatic difference in the positive rates at the ulcer margin was observed between gastric and duodenal ulcer patients (83.9% and 35.0%, respectively). The prevalence of polymorphonuclear (PMN) cell infiltration at the ulcer margin was still high even at the scarring stage of gastric and duodenal ulcer with positive H. pylori, whereas a dramatic decrease of PMN cell infiltration was observed at the ulcer margin after successful eradication of H. pylori. These results suggest that H. pylori may play an important role in the pathogenesis of gastric and duodenal ulcer by inducing inflammatory cells such as PMN cells in gastric mocosa. PMID- 8359626 TI - Histological patterns of prolonged hepatitis C infection. AB - Liver biopsies from 63 patients with hepatitis C virus (HCV) infection have been studied. 31 were asymptomatic and had been detected by a variety of screening programs, and most of the other 32 had complained of vague symptoms only. In 57 patients a confident estimate of the duration of infection was able to be made (ranging from 12 months to over 38 years) and 73% of these had been infected for over 5 years. The most common histological pattern observed was a low-grade panacinar hepatitis. This affected 74.6% of all biopsies, and 43% of this group had been infected for over 10 years. Severe chronic active hepatitis and/or cirrhosis occurred in only 8% of the whole series, and in 16.7% of those infected for over 10 years. This incidence of serious sequelae in chronic HCV infection is much lower than previously reported, probably reflecting the methods of patient selection, and may represent more accurately the natural history of the disease in this community. The occurrence of a number of characteristic histological features (lymphoid follicles and aggregates, steatosis, Kupffer cell prominence, and apoptotic or acidophilic bodies) was confirmed, the constellation of which is highly suggestive of HCV infection. It is suggested that apoptosis may play an important role in the perpetuation of HCV as a chronic infection. PMID- 8359627 TI - Ethics in the aging population: a gastroenterologist's perspectives. PMID- 8359628 TI - Current ethical problems in Japan. PMID- 8359629 TI - Liver transplantation: the Danish experience. PMID- 8359630 TI - Liver transplantation: the Australian experience. PMID- 8359631 TI - Current status of liver transplantation (LT) in France and specificities of French ethical attitudes concerning LT. AB - The authors report first on the current status of liver transplantation in France and underline its exponential development. The main indications for this procedure are outlined for adults as well as for children. The modalities of distribution of livers harvested by strictly controlled university teams are also briefly described. The specificities of French ethical attitudes towards liver transplantation are discussed. They concern the donor, the recipient and the society. Legal dispositions stipulating the presumed consent of the donor and accrediting the notion of "cerebral death" have eased the development of liver transplantation in France. Despite these measures shortage in liver available for grafts results in still too large waiting list and fosters nation-wide campaign to encourage organ donation. There is, in France, a strong consensus for a strict sticking to the absolute principles of gratuity of organ donation and non marketing of excised organs available for graft. As stated recently by Thomas Starzl, liver transplantation has become the second most commonly performed solid organ transplant after kidney transplant. In the latin Europe, the idea of organ transplantation is in the mind of people for a long time as illustrated from paintings or carvings that can still be seen in several roman catholic churches of the Middle Age. Although, liver transplantation in man developed only after the pioneer work of Thomas Starzl in Pittsburg, it is fair to recall that Alexis Carrel (1908, Noble Prize), from France, opened the way to organ transplantation by performing in animals the first vascular sutures and organ auto- or homografts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359632 TI - Education in medical ethics. AB - Since ethics is an integral part of practice of medicine, its study should parallel that of study of medicine. It should proceed in an orderly fashion from undergraduate into postgraduate study, starting with an understanding of principal moral values governing medical ethics. It should subsequently develop awareness of frequent existence of ethical issues and dilemmas, help develop the capacity for resolution of these issues through ethical reasoning, and acquire understanding of the function of institutional bodies concerned with ethics. Clinical real life situations and case studies should be extensively used as an educational tool. The exact design of the curriculum may vary to reflect the medical curriculum of a particular institution, but common objectives to all systems must be to achieve familiarity with moral values underlying the practice of medicine and with methodology of ethical reasoning. Some form of examination and evaluation of the course should be a standard feature of all teaching programs of medical ethics. PMID- 8359633 TI - Liver transplantation in Italy and the scarcity of donors: causative factors and ethical considerations. AB - We analyze the current state of liver transplantation (OLTx) in Italy that in the last few years had reached approximately 150 OLTx per year for a population of 58 millions of inhabitants. The need for OLTx in Italy is high and mainly due to the incidence of post-hepatitis and post-alcoholic liver cirrhosis, which are the prevalent indication for OLTx. On the contrary the availability of donor organs in Italy is very low as compared with other European countries, and as a consequence the gap between need and performed OLTx is widening. The reasons for poor donations are multifactorial among which; lack of organization, insufficient ICU care beds, poor knowledge of health personnel. General attitudes of the society and brain death concepts are also involved as a recent survey has demonstrated. Under certain circumstances the patient who cannot be transplanted on time in Italy is allowed to seek for care abroad under the local government economical assistance. Finally some ethical considerations and the proposal for better education of both population and health care providers are advocated. PMID- 8359634 TI - Orthotopic liver transplantation in Canada. PMID- 8359635 TI - Ethical issues and liver transplantation in the United States of America. PMID- 8359636 TI - Promotion of ethics in gastroenterology. Joint meeting of the members of the Japanese Society of Gastroenterology and the World Organization of Gastroenterology. PMID- 8359637 TI - Gastrointestinal hormones: past, present, and future. PMID- 8359638 TI - Anal dysplasia in homosexual men: role of anoscopy and biopsy. AB - BACKGROUND: Both anal squamous cell cancer and human papilloma virus (HPV) are increased in homosexual men. This study evaluates histology of internal anal abnormalities in a high-risk population of human immunodeficiency virus (HIV) seropositive and seronegative homosexual men. METHODS: Ninety men with abnormalities of the internal anal canal (referred from a cross-sectional study of 512 homosexual men) were evaluated by anoscopy, anal cytology, and directed biopsy. CD4 cell counts from blood and HPV types from anal tissue were also obtained. RESULTS: Seventy-eight (86%) men had HPV-associated abnormalities: discrete warts in 39 (43%), a wart ring in 23 (26%), and flat white epithelium in 18 (20%). Dysplasia was detected by cytology in 36% and by biopsy in 92% (27% high grade). High-grade dysplasia was equally common in HIV-seropositive and seronegative men. The morphology of anal lesions did not predict the presence of dysplasia. Both high- and low-risk HPV types were common in many of the biopsy specimens. CONCLUSIONS: Anal dysplasia is common in biopsy specimens from homosexual men with visible HPV-associated internal anal abnormalities. Natural history studies are needed to determine the clinical significance of anal dysplasia, rates of progression to cancer, and the role of screening and therapy. PMID- 8359639 TI - Simultaneous assessment of liquid emptying and proximal gastric tone in humans. AB - BACKGROUND: Barostat is the only technique that allows assessment of gastric tone in humans. Our aim was to simultaneously assess gastric emptying and relaxation in response to a liquid meal. METHODS: Gastric tone was monitored using an electronic barostat in six healthy subjects after three liquid meals (200 mL, 400 mL, 600 mL, 1 kcal/mL). Scintigraphic imaging was obtained by using double isotopic labeling (technetium 99m for liquid of the 200 mL meal and xenon 133 for air into the barostat). RESULTS: Profound gastric relaxation was detected in every subject. The duration of proximal gastric relaxation increased with meal size. The proximal stomach remained relaxed through the duration of gastric emptying. Gastric tone returned to the fasting values simultaneously with completion of liquid emptying. Repeated measures after the 200-mL meal showed that amplitude (i.e., maximal volume change) and duration of relaxations were reproducible. However, the presence of the bag slightly accelerated gastric emptying and modified the intragastric distribution of the meal. CONCLUSIONS: The barostat is a sensitive and reproducible technique to measure gastric relaxation following liquid meals in humans. The results also suggest that the role of gastric tone as the driving force of gastric emptying of liquids has been overestimated. PMID- 8359640 TI - Growth failure in children with inflammatory bowel disease: a prospective study. AB - BACKGROUND: Growth failure frequently complicates the clinical course of inflammatory bowel disease (IBD) in children. This study was designed to investigate the role of disease activity versus steroid therapy on growth faltering in this disorder. METHODS: We studied growth failure and its relationship to disease activity and steroid therapy in 69 children who have IBD by prospectively monitoring height for a maximum of 3 years. Disease activity and steroid use were recorded at entry into the study. RESULTS: The prevalence of growth failure was 24%, 23%, and 39% by height velocity, Z score, and height-for age criteria, respectively; deficits were equally prevalent regardless of the stage of pubertal development. A delay in linear growth persisted throughout puberty and was not reversed after surgery. Patients who had Crohn's disease were twice as likely to have growth abnormalities than patients who had ulcerative colitis. We detected significant negative associations between linear growth and disease activity but not steroid therapy. CONCLUSIONS: In a unique group of children, growth failure is an early, "prepatterned" manifestation of IBD. The inflammatory process, rather than steroid use, has a predominant influence on the development of growth faltering. PMID- 8359641 TI - Inhibition of glucose absorption by phlorizin affects intestinal functions in rats. AB - BACKGROUND: To investigate the mechanism of regulation of intestinal disaccharidase activity and glucose absorption, the effect of dietary intake of phlorizin, a potent and specific inhibitor of intestinal glucose transport, on intestinal disaccharidase activity and Na(+)-dependent glucose transporter was examined in rats. METHODS: Jejunal disaccharidase activity and the number of Na(+)-dependent glucose transporters were determined in rats maintained on a low starch diet, a high-starch diet, or low-starch diets containing various amounts of phlorizin (0.1%-0.9% wt/wt). RESULTS: Jejunal disaccharidase activity increased in a dose- and time-dependent manner. Stimulation of jejunal disaccharidase activity only occurred when phlorizin was added to starch containing diets, not when it was added to a carbohydrate-free diet. Addition of the same amount of phloretin and glucose (constituents of phlorizin), to the diet failed to increase disaccharidase activity. The maximum binding of phlorizin to brush border membrane vesicles was increased in the rats fed phlorizin, whereas the dissociation constant remained unchanged, suggesting an increase of glucose transporter expression. CONCLUSIONS: Dietary phlorizin increased the jejunal disaccharidase activity and Na(+)-dependent glucose transporter expression. The trigger for these changes may have been due to an increased luminal glucose content. PMID- 8359642 TI - Surface staining on the villus of lactase protein and lactase activity in adult type hypolactasia. AB - BACKGROUND: We have shown in previous studies the presence of a patchy pattern of lactase protein expression in the proximal jejunum of hypolactasic humans, adult rabbits, and rats. The present study investigated the mechanisms underlying the heterogeneous expression of lactase on the villus. METHODS: Proximal jejunal tissue from 18 adult humans and 12 adult rabbits was examined using enzymocytochemical and surface-staining techniques for lactase protein and activity. RESULTS: In the proximal jejunum of hypolactasic humans and adult rabbits, lactase activity is patchily distributed on the villus enterocytes. In humans, the patches of lactase-positive enterocytes are randomly distributed on the villus, whereas in rabbits, vertical, continuous sheets of positive enterocytes arise from the base of the villus. CONCLUSIONS: The presence of enterocytes without lactase activity is one of the mechanisms causing adult-type hypolactasia in the proximal jejunum of humans and mammals. The patchy pattern of lactase in rabbits suggests a clonal origin with heterogeneity of the cells arising from the crypts. In hypolactasic humans, the enterocyte heterogeneity occurs as a consequence of mechanisms that do not have a clonal origin. PMID- 8359644 TI - Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY. AB - BACKGROUND: Upper gastrointestinal motility is regulated by the presence of nutrients in the distal gut. The present study evaluated whether lipid-induced ileal brake on gastric emptying (1) can be elicited by low fat concentrations; (2) is a dose-dependent phenomenon; and (3) is related to gastrointestinal peptide release. METHODS: Seven patients were studied in the defunctionalized stage of total colectomy, on three separate occasions. On each study day, patients ate a meal labeled in the solid component; 30 minutes later, one of the following solutions was randomly infused into the ileal pouch: 0.9% saline, 2% oleic acid, and 20% oleic acid. Plasma concentrations of peptide YY (PYY), enteroglucagon, neurotensin, and motilin were measured. RESULTS: Both oleic acid solutions slowed gastric emptying compared with saline (P < 0.001), the effect being dose dependent (P < 0.001). Ileal infusions did not modify neurotensin and enteroglucagon levels but induced a dose-dependent increase of PYY (P < 0.01) and a borderline decrease of motilin (P = 0.05) levels. Slower rates of gastric emptying were related to increased plasma concentrations of PYY (r = 0.615; P < 0.05). CONCLUSIONS: This study shows that (1) the ileal brake on gastric emptying can be evoked by low doses of lipids in the distal ileum; (2) the delay of gastric emptying is related to the release of PYY; and (3) both phenomena are dose dependent. PMID- 8359643 TI - Bicarbonate-stimulated [14C]butyrate uptake in basolateral membrane vesicles of rat distal colon. AB - BACKGROUND: The mechanism of short-chain fatty acid (SCFA) absorption by the colon is not known. The aim of these experiments was to identify the transport mechanisms present in the basolateral membrane to develop an overall model of colonic SCFA absorption. METHODS: These studies determined the uptake of [14C]butyrate (used as a model SCFA) by basolateral membrane vesicles prepared from rat distal colonic mucosa. RESULTS: Significantly higher [14C]butyrate uptake under an acidic environment (extravesicular pH [pHo] = intravesicular pH [pHi] = 5.5) than that under alkaline environment (pHo = pHi = 7.5) indicates the presence of nonionic diffusion. In the absence of a pH gradient (pHo/pHi = 7.5/7.5), outward gradients of bicarbonate significantly stimulated [14C]butyrate uptake. Additional presence of a pH gradient (pHo/pHi = 6.0/7.5) further enhanced the bicarbonate gradient-stimulated [14C]butyrate uptake that was not inhibited by voltage clamping but was inhibited substantially by an anion exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) (82%). Both increasing extravesicular butyrate concentration and intravesicular bicarbonate concentration saturated bicarbonate/pH gradient-stimulated [14C]butyrate uptake with an apparent Michaelis constant (Km) for butyrate of 6.9 mmol/L and an apparent Km for bicarbonate of 27.4 mmol/L. CONCLUSIONS: Butyrate uptake by basolateral membrane vesicles represents both nonionic diffusion and a carrier mediated SCFA-bicarbonate exchange process that differs from the SCFA-bicarbonate exchange recently identified in apical membrane vesicles. Thus, two distinct carrier-mediated anion exchange processes located in apical and basolateral membranes mediate transcellular SCFA transport in colonocytes. PMID- 8359645 TI - Effect of crural myotomy on the incidence and mechanism of gastroesophageal reflux in cats. AB - BACKGROUND: Esophagogastric junction (EGJ) pressure is the major barrier to gastroesophageal reflux. Recent studies suggest that contraction of the crural diaphragm increases esophagogastric junction pressure. Whether this increase in EGJ pressure is important in the prevention of gastroesophageal reflux is not known. Our aim in this study was to determine the effects of crural myotomy on the occurrence of gastroesophageal reflux. METHODS: The spontaneous and stress gastroesophageal reflux before and after a surgical crural myotomy in four cats was studied. Spontaneous gastroesophageal reflux was recorded in the awake cats through a pH probe, placed via an esophagostomy, for periods of 12-24 hours. Stress reflux was studied during periods of airway obstruction and abdominal compression in anesthetized animals using the technique of simultaneous esophageal manometry and pH monitoring. RESULTS: There was a significant increase in the frequency of spontaneous acid reflux after crural myotomy. In anesthetized animals, there was an increase in the EGJ pressure during airway obstruction, which was abolished by a crural myotomy. Abdominal compression caused a reflex contraction at the EGJ that was not affected by crural myotomy. The crural myotomy resulted in a significant increase in the frequency of acid reflux during airway obstruction but not during abdominal compression. CONCLUSIONS: It is concluded that the crural diaphragm is important in the prevention of gastroesophageal reflux and its dysfunction leads to an increased incidence of gastroesophageal reflux. PMID- 8359646 TI - Duodenal pH dips as an index of transpyloric flow in conscious dogs. AB - BACKGROUND: To determine if duodenal pH fluctuations might be used as a valuable index of the occurrence of gastric chyme ejection, the transpyloric flow and pH in the duodenal bulb were monitored simultaneously in six dogs. METHODS: Transpyloric flow, monitored by a chronically implanted electromagnetic flowmeter, was represented by individual pulses of flow. Relations between the volume of these flow pulses and changes in duodenal pH were assessed both postprandially and during the increased gastric outflow that followed gastric loading of buffered saline solutions at pH 2 and 4. RESULTS: During fasting and gastric loading with buffered saline at pH 2, no consistent relationship between flow pulses and duodenal pH fluctuations was evident. After instillation of buffer solution at pH 4 and postprandially, the magnitude of duodenal pH fluctuations became proportional to the stroke volume of the flow pulses. The removal of bile from the proximal duodenum decreased the relationship. CONCLUSIONS: It is concluded that duodenal pH measured at 2 cm from the pylorus might be used postprandially as an index of the transpyloric flow rate of chyme. PMID- 8359647 TI - Anti-immunoglobulin E-stimulated ion transport in human large and small intestine. AB - BACKGROUND: Mast-cell regulation of intestinal ion transport, previously shown in animals and cultured cells, was examined in surgically resected human bowel in this study. METHODS: Changes in short-circuit current (Isc) in response to rabbit anti-human immunoglobulin (Ig) E or control serum, histamine, and electrical stimulation were measured in muscle-stripped, noninflamed segments of intestine mounted in Ussing chambers. Chloride-free buffer, pyrilamine, piroxicam, sodium cromoglycate, and tetrodotoxin were examined for their effect on Isc responses to these stimuli. RESULTS: Within 1-2 minutes of adding anti-IgE serum, a specific monophasic rise in Isc (peaking at 7-10 minutes) was observed in large and small intestine. This response was reduced approximately 80% in chloride-free buffer and inhibited by the histamine1-receptor antagonist, pyrilamine, and the cyclo oxygenase inhibitor, piroxicam, implicating histamine and prostaglandins as mediators of the ion transport changes. The mast-cell stabilizer, sodium cromoglycate, reduced anti-IgE responses in the small, but not large, intestine. Approximately 50% inhibition of anti-IgE responses in colon by the neurotoxin, tetrodotoxin, indicated that nerves were involved. CONCLUSIONS: These results suggest that activation of mast cells releases mediators that stimulate intestinal ion transport through direct epithelial action and via nerves. This study provides important evidence that immunoregulation of intestinal ion transport does occur in humans. PMID- 8359648 TI - 5-hydroxytryptamine-3 receptors are involved in the initiation of gastric phase-3 motor activity in humans. AB - BACKGROUND: 5-hydroxytryptamine-3 (5-HT3) receptor antagonists inhibit gastric phase-3 motor activity in the dog. This study examined the role of 5-HT3 receptors in the generation of gastric phase 3 of the migrating motor complex in humans. METHODS: Interdigestive motor activity was recorded manometrically in 16 subjects before and after administration of ondansetron, a selective 5-HT3 receptor antagonist. Plasma motilin values were also assayed in 7 individuals. The incidence of gastric activity fronts before and after ondansetron was compared with a control group that had not received ondansetron. The ability of erythromycin to induce a gastric activity front in the presence of ondansetron was also evaluated in 7 subjects. RESULTS: The incidence of gastric activity fronts was 69% before ondansetron vs. 19% after ondansetron. In contrast, in the control group there was no significant change in the incidence of gastric activity fronts over time. Activity fronts preceding ondansetron were associated with motilin peaks while activity fronts after ondansetron were not. Despite the previous administration of ondansetron, erythromycin induced gastric activity fronts in 89% of cases. CONCLUSIONS: Selective antagonism of 5-HT3 receptors suppresses the gastric component of phase-3 motor activity and simultaneously suppresses plasma motilin peaks. The results suggest that the suppression of gastric activity fronts is achieved via the suppression of plasma motilin peaks because in the presence of ondansetron a motilin agonist like erythromycin restores the gastric phase 3. PMID- 8359649 TI - Functional constipation and outlet delay: a population-based study. AB - BACKGROUND: Chronic constipation may result from many mechanisms including colonic inertia or rectosigmoid outlet delay, but risk factors for constipation in the community are poorly defined. The prevalence of and predictors for symptoms consistent with functional constipation and outlet delay were estimated. METHODS: An age- and gender-stratified random sample of 1,021 residents of Olmsted County, MN, aged 30-64 years, was mailed a valid self-report questionnaire; 835 responded (82%). These respondents were mailed a second questionnaire 12-20 months later that gathered data on symptoms compatible with functional constipation and outlet delay; 690 responded (83%). RESULTS: Self reported constipation did not reliably identify functional constipation or outlet delay. The overall age- and gender-adjusted prevalences (per 100) of functional constipation and outlet delay were 19.2 (95% confidence interval [CI], 16.1-22.3) and 11.0 (95% CI, 8.7-13.3), respectively. Outlet delay but not functional constipation was more frequent in women. After adjusting for age, gender, and other symptoms, an increased usage of aspirin was associated with functional constipation but not outlet delay. CONCLUSIONS: In apparently healthy middle-aged persons, approximately 1 in 5 have symptoms compatible with functional constipation, and 1 in 10 may experience outlet delay, but these groups correspond poorly with self-reported constipation. PMID- 8359650 TI - The motor response to intestinal resection: motor activity in the canine small intestine following distal resection. AB - BACKGROUND: The mucosal response to intestinal resection has been extensively studied; little is known of the motor response. Our aim was to evaluate motility in the intestinal remnant following distal resection. METHODS: Motor activity, duodenocecal transit, nutrition, and absorption were studied over a 3-month period in control animals (n = 9) and in groups of dogs who had undergone 25% (n = 6), 50% (n = 5), and 75% (n = 5) distal resection. RESULTS: Diarrhea and steatorrhea developed in each resection group, and the 75% group alone developed true short bowel syndrome. Resection did not affect migrating motor complex frequency or periodicity; phase 1 duration was shorter in the 75% group (control vs. 75%: 22 +/- 4 vs. 6 +/- 2 minutes, P < 0.03). The most striking motor effect was the development of prominent cluster activity in the distal part of the remnant in 25% and 50% resection animals and throughout the remaining intestine in the 75% group. Duodenocecal transit slowed during the study period from 13 +/- 1 to 20 +/- 2 minutes in the 50% and from 10 +/- 2 to 14 +/- 2 minutes in the 75% group (P < 0.05). CONCLUSIONS: The initial motor response to major resections of the distal small intestine is dominated by the development of abnormal patterns. This motor disruption may contribute to the symptomatology and clinical features of the short bowel syndrome. PMID- 8359651 TI - Flow cytometry and Zollinger-Ellison syndrome: relationship to clinical course. AB - BACKGROUND: With successful means of controlling gastric acid secretion in patients with Zollinger-Ellison syndrome, the gastrinoma itself is becoming the major determinant of long-term survival. No methods have yet been described to predict which tumors will have more malignant courses thereby indicating which patients should undergo aggressive surgery or antitumor therapy. Because DNA analysis, using flow cytometry, has proved helpful in this regard in other tumors, the current study was designed to evaluate its utility in gastrinoma patients. METHODS: Flow cytometry was performed on 81 paraffin-embedded gastrinoma specimens from 59 patients. Results were compared with preoperative patient characteristics, findings at surgery, and postoperative follow up. RESULTS: Tumors were diploid in 54% of patients, near diploid in 15%, pure tetraploid in 0%, nontetraploid aneuploid in 25%, and multiple stem line aneuploid in 5%. All patients with multiple stem line aneuploid tumors had wide spread metastases whereas all patients with nontetraploid aneuploid tumors had localized or regional disease. Median S phase percentage was 3.6. S phase percentages were higher in patients with widespread metastatic disease than in patients with localized or regional disease. Disease extent also correlated closely with fasting serum gastrin level. After removing this variable with logistic regression analysis, the significant correlation between disease extent and DNA analysis persisted. CONCLUSIONS: DNA analysis of gastrinoma tissue specimens correlates independently with the extent of disease and may be useful in planning therapeutic strategies for patients with Zollinger-Ellison syndrome. PMID- 8359652 TI - The significance of carbonic anhydrase expression in human colorectal cancer. AB - BACKGROUND: Carbonic anhydrase isoenzymes I and II are present in normal colorectal mucosa. This study aimed to determine if carbonic anhydrase is present in colorectal cancer and what is its potential clinical significance. METHODS: The messenger RNA (mRNA) and protein expression of carbonic anhydrase isoenzyme I were analyzed in fresh specimens of colorectal adenocarcinoma by Northern and Western blots, respectively. The immunohistochemical expression was subsequently studied in a larger number of formalin-fixed surgical specimens. RESULTS: All of 30 normal colon samples had a strong RNA hybridization signal. Only 4 of 39 paired colorectal cancer and none of 9 normal liver samples had detectable levels of carbonic anhydrase mRNA. Isoenzyme I protein expression showed similar results. In a separate group of patients, immunohistochemical studies showed that 16 of 96 colorectal tumors had positive staining cells. All positive tumors were well or moderately differentiated carcinomas (P < 0.05). When analyzed retrospectively, immunoreactive cases were more likely to be in a group with a good outcome (P < 0.01) and to lack vascular invasion (P < 0.01) than negative cases. CONCLUSIONS: The majority of colorectal cancers do not express carbonic anhydrase isoenzyme I. The presence of any isoenzyme I-positive immunoreactive cancer cells may be associated with a more favorable outcome in colorectal cancer. PMID- 8359653 TI - Sucrase-isomaltase gene expression in Barrett's esophagus and adenocarcinoma. AB - BACKGROUND: Specialized Barrett's esophageal mucosa, characterized by incomplete intestinal metaplasia of the esophageal mucosa, is associated with the development of adenocarcinoma. Although the intestinal disaccharidase sucrase isomaltase (SI) has been shown in incomplete intestinal metaplasia of the stomach, it is commonly believed that Barrett's mucosa does not express SI based on the lack of enzymatic activity. This study was undertaken to determine whether the SI gene is expressed in Barrett's epithelium and its associated adenocarcinoma at the level of messenger RNA (mRNA) and protein. METHODS: Reverse transcription polymerase chain reaction was used to determine the presence of SI mRNA in Barrett's esophagus and esophageal adenocarcinomas. Cellular localization of SI protein was determined by immunohistochemistry. RESULTS: SI mRNA was identified in 76% of Barrett's epithelium and 82% of esophageal adenocarcinomas. The transcriptional initiation site for SI in these tissues was identical to that of the small intestine. Immunohistochemical localization showed that SI was directed to the apical membrane in Barrett's epithelium in contrast to a more diffuse cytoplasmic pattern in esophageal adenocarcinomas. CONCLUSIONS: Columnar cells of specialized Barrett's epithelium express SI and are, therefore, phenotypically similar to those in incomplete intestinal metaplasia of the stomach with respect to intestinal gene expression. PMID- 8359654 TI - Hepatic encephalopathy in rats with thioacetamide-induced acute liver failure is not mediated by endogenous benzodiazepines. AB - BACKGROUND: To distinguish whether the improvement of hepatic encephalopathy by benzodiazepine receptor antagonists is mediated by their antagonistic or their inverse agonistic properties, the neurobehavioral effects of a variety of benzodiazepine receptor ligands in rats with thioacetamide-induced acute liver failure were tested. METHODS: The neural inhibitory effect of the benzodiazepine agonist flunitrazepam and its reversibility by the "pure" antagonist Ro 14-7437 were examined in thioacetamide-treated rats and controls. The effects of Ro 14 7437, of the partial inverse agonist Ro 15-4513, and the inverse agonist DMCM in rats with hepatic encephalopathy grade II/III were tested. Encephalopathic rats were pretreated with Ro 14-7437 or vehicle and then injected with Ro 15-4513. RESULTS: Thioacetamide-treated rats were more sensitive to flunitrazepam than controls. In both groups, its effect was completely antagonized with Ro 14-7437. Encephalopathy was significantly improved by Ro 15-4513, although Ro 14-7437 and vehicle had no effect. DMCM worsened the condition of encephalopathic rats but had no effect in controls. Pretreatment with Ro 14-7437 abolished the beneficial effects of Ro 15-4513. CONCLUSIONS: In rats with thioacetamide-induced liver failure, endogenous benzodiazepines do not precipitate hepatic encephalopathy. The amelioration of hepatic encephalopathy is mediated by benzodiazepine receptor ligands with both antagonistic and inverse agonistic properties. PMID- 8359655 TI - Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans. AB - BACKGROUND: The aim of this study was to quantitatively evaluate the relative contributions to in vivo lipolysis of gastric and pancreatic lipases. METHODS: Gastric and pancreatic lipase secretions were measured, and their respective levels were determined in duodenal fluid during the digestion of a liquid test meal in healthy volunteers. Gastric lipase activity was clearly distinguished from that of pancreatic lipase by using both a specific enzymatic assay and an enzyme-linked immunosorbent assay. Lipolysis products were monitored throughout the digestion period. RESULTS: On a weight basis, the ratio of pancreatic lipase to gastric lipase total secretory outputs was found to be around four after 3 hours of digestion. The level of gastric hydrolysis was calculated to be 10% +/- 1% of the acyl chains released from the meal triglycerides. Gastric lipase remained active in the duodenum where it might still hydrolyze 7.5% of the triglyceride acyl chains. CONCLUSIONS: Globally during the whole digestion period, gastric lipase might hydrolyze 17.5% of the triglyceride acyl chains. In other words, gastric lipase might hydrolyze 1 acyl chain of 4, which need to be hydrolyzed for a complete intestinal absorption of monoglycerides and free fatty acids resulting from the degradation of two triglyceride molecules. PMID- 8359656 TI - Bile acid-dependent vesicular transport of lysosomal enzymes into bile in the rat. AB - BACKGROUND: Bile acids may stimulate the movement of hepatocyte vesicles and enhance their fusion with the biliary canaliculus. The present study examined the effects of various bile acids on the exocytosis of the contents of hepatocyte lysosomes into the biliary canaliculus. METHODS: The effects of various bile acids on hepatocyte lysosome movement and on exocytosis of the contents of hepatocyte lysosomes into the biliary canaliculus were determined from the distribution of fluorescein isothiocyanate-dextran--labeled lysosomes in hepatocyte couplets and by quantitating biliary lysosomal enzyme output in rats. RESULTS: Hydrophobic as well as hydrophilic and nonmicellar bile acids were found to stimulate to a similar degree the output of lysosomal enzymes into bile, indicating that bile acid-induced change of canalicular or lysosomal membrane fluidity is not responsible for enhanced exocytosis. The taurocholate-dependent increase in lysosomal enzyme excretion was completely blocked by either microtubule or microfilament inhibition, suggesting that these subcellular structures are involved in bile acid-dependent vesicular transport. Fluorescent microscopy studies showed that taurocholate causes a microtubule-dependent translocation of lysosomes towards the canaliculus in hepatocyte couplets, which occurred at the same time as increased output of lysosomal enzymes into bile. CONCLUSIONS: The results suggest that bile acids modulate vesicle traffic towards the canaliculus by a mechanism unrelated to bile acid interaction with the vesicle membrane. PMID- 8359657 TI - Fibrosing cholestatic hepatitis in a transplant recipient with hepatitis B virus precore mutant. AB - A patient with hepatitis B virus (HBV) precore mutant (seropositive for hepatitis B surface antigen [HBsAg], anti-hepatitis B e antigen [HBeAg], and HBV DNA) who underwent orthotopic liver transplantation for end-stage liver disease is described. Sequencing of the HBV precore region of the pretransplant serum sample confirmed the presence of the precore stop-codon mutant (G-->A mutation in codon 1896) only. The patient received HBV immunoglobulin prophylaxis for 6 months but HBV recurred thereafter with a mild hepatitic flare, and he remained seropositive for HBsAg, anti-HBe, and HBV DNA. The initial hepatitic illness resolved in 3 months. The patient remained well for another 16 months before presenting with fibrosing cholestatic hepatitis (FCH). During his entire initial hepatitic flare, quiescent period, and final FCH phase, he remained seropositive for HBsAg, anti HBe, and HBV DNA. Moreover, sequencing of the serum HBV DNA in final FCH phase showed the presence of the identical HBV precore mutant. Immunohistochemical staining showed extensive expression of HBsAg/pre-S1, pre-S2, and hepatitis B core antigen, but HBeAg was scarcely detectable. This case illustrates that (1) recurrence of HBV precore mutant infection can occur in liver; (2) it can give rise to FCH; and (3) hepatic accumulation of HBeAg is not essential for the development of FCH. PMID- 8359658 TI - Abdominal radiotherapy is a cause for chronic pancreatitis. AB - We report a series of five patients with nonalcoholic chronic pancreatitis who underwent abdominal radiotherapy for Hodgkin's disease (n = 4) or seminoma (n = 1) at doses ranging from 3600 to 4050 rads, 6 to 20 years (median, 7 years) before the onset of pancreatitis. Patients were in complete remission for their malignant disease. Other causes of chronic pancreatitis were excluded. The manifestations of chronic pancreatitis (median follow-up after the diagnosis of pancreatitis, 5 years) were pancreatic pain (n = 5), acute pancreatitis (n = 3), pseudocysts (n = 3), common bile duct stenosis (n = 2), duodenal stenosis (n = 1), splenic vein obstruction (n = 1), diabetes mellitus (n = 4), steatorrhea (n = 4), and pancreatic calcifications (n = 1). Other abdominal radiation injuries were severe chronic ulcer of the genu superius (n = 1), stenosis at the junction of the right and left hepatic ducts (n = 1), and splenic and left renal atrophy (n = 1). In one patient, pathological examination of the pancreas showed signs of chronic pancreatitis, severe fibrous endarteritis, and lack of inflammation. Abdominal radiotherapy should be added to the list of causes of chronic pancreatitis. We suggest that the physiopathology of postradiotherapy chronic pancreatitis is a vascular process. PMID- 8359659 TI - HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis. AB - The overrepresentation of particular HLA alleles in patients with celiac disease was first noted two decades ago. Several lines of evidence obtained during the last years strongly suggest that a particular HLA-DQ heterodimer, encoded by the DQA1*0501 and DQB1*0201 genes in cis or trans configuration, confers the primary disease susceptibility. This paper reviews the evidence behind this concept and discusses how this particular DQ molecule may be involved in the pathogenesis. PMID- 8359660 TI - Intestinal lactase: what defines the decline? PMID- 8359661 TI - Neuroimmune regulation of human intestinal transport. PMID- 8359662 TI - Hiatal hernia and gastroesophageal reflux: another attempt to resolve the controversy. PMID- 8359663 TI - ANCAs aweigh in colitis. PMID- 8359664 TI - Dietary risk factors and colorectal polyps: apparently gender does make a difference. PMID- 8359665 TI - Feedback regulation of intracellular calcium release. PMID- 8359666 TI - Reversal of hypersplenism after liver transplantation. PMID- 8359667 TI - Deoxycholic acid metabolism in patients with adenomas. PMID- 8359668 TI - Role for thalidomide in primary biliary cirrhosis treatment? PMID- 8359669 TI - Gut permeability and disease severity in acute pancreatitis. PMID- 8359670 TI - Prostaglandin E2 effects on duodenal electrical conductance. PMID- 8359671 TI - Cloning and nucleotide sequence analysis of the Candida albicans enolase gene. AB - The complete nucleotide sequence of the coding region as well as the flanking non coding region of Candida albicans enolase gene was determined. A continuous open reading frame of 1323 nucleotides with no introns was identified. The deduced amino acid sequence showed 87% similarity to the enolases from the yeast Saccharomyces cerevisiae. The two isoforms of enolase are encoded by two non tandemly arrayed genes in S. cerevisiae. However, DNA hybridisation analysis indicates that in C. albicans enolase is encoded by a single gene. The position of the transcription start site, putative TATA box and polyadenylation signal of the C. albicans enolase gene have been identified. The location of these sequences are similar to those of the S. cerevisiae enolase genes. PMID- 8359672 TI - Unique genetic arrangement in the dnaA region of the Borrelia burgdorferi linear chromosome: nucleotide sequence of the dnaA gene. AB - The complete nucleotide sequence of the Borrelia burgdorferi dnaA gene (encoding the initiator protein of chromosome replication) and its flanking regions was determined. The putative DnaA polypeptide exhibited 29-42% identity with those of other eubacteria. The gene order in the dnaA region at the centre of the B. burgdorferi linear chromosome is rnpA-rpmH-dnaN-dnaA-gyrB-gyrA in contrast to the consensus eubacterial order of rnpA-rpmH-dnaA-dnaN-recF-gyrB, suggesting a rearrangement during the evolution of the Borrelia chromosome. We did not detect the multiple 9-nucleotide repeats known as DnaA boxes, which characterise origin of replications, in the dnaA-gyrB and dnaA-dnaN intergenic regions. In addition B. burgdorferi DnaA protein differs considerably from those of other eubacteria in a normally highly conserved region at the C-terminus of the polypeptide which may be involved in DNA binding. PMID- 8359673 TI - Agr-related sequences in Staphylococcus lugdunensis. AB - Sequences related to the Staphylococcus aureus accessory gene regulator (agr) were demonstrated in S. lugdunensis by Southern blot analysis of 13 strains and sequencing of the S. lugdunensis agr-like locus (agr-sl). Northern blot analysis of cellular RNA revealed the presence of a transcript having homology with the agr-P3 transcript (RNAIII) for three of the six strains tested. The three strains containing this transcript produce a hemolysin with phenotypic properties similar to that of S. aureus delta-hemolysin. Nevertheless, unlike agr-P3 from S. aureus, agr-sl does not encode any potential peptide homologous to S. aureus delta hemolysin, suggesting that the hemolytic activity detected in S. lugdunensis is encoded elsewhere and may be controlled by agr-sl. PMID- 8359674 TI - Phototaxis genes on linkage group V in Dictyostelium discoideum. AB - During the course of mapping and complementation analysis of phototaxis (pho) mutations in Dictyostelium discoideum we have assigned to linkage group V three mutant pho alleles belonging to complementation groups phoG and phoK. These are the first genetic markers with an easily recognizable phenotype to be found on this linkage group. PMID- 8359675 TI - Identification of the mcrC gene product in Methanococcus vannielii. AB - The polypeptide encoded by the mcrC gene has been identified in Methanococcus vannielii by immunoblotting using rabbit antibodies raised against the product of a lacZ-mcrC gene fusion synthesized and purified from Escherichia coli. The mcrC gene product (gpmcrC) was located in both the supernatant and pellet fractions after centrifugation of Mc. vannielii cell extracts for 2 h at 100,000 x g. When anaerobic reducing conditions were maintained during purification, gpmcrC co sedimented through sucrose gradients to the same position as molecules of the methyl coenzyme M reductase holoenzyme (approx. 300 kDa). This co-sedimentation was lost under aerobic, nonreducing conditions. PMID- 8359676 TI - Construction of genetically marked Vibrio cholerae O1 vaccine strains. AB - Attenuated Vibrio cholerae O1 vaccine strains lacking the gene encoding the A subunit of cholera toxin have proven efficacious in preventing experimental cholera. As these strains move from closed, contained testing environments to large-scale field trials, a readily assayable phenotypic trait to distinguish a vaccine strain from wild-type V. cholerae O1 is desirable. We have constructed three derivatives of the attenuated V. cholerae strain CVD 103 which carry a mercury resistance or urease marker in the hlyA gene. CVD 103-HgR was constructed using a protracted marker-exchange procedure; this strain was found to have somewhat lowered colonisation efficiency in infant mice in comparison to its parent strain, CVD 103. The insertion of the resistance marker was repeated using a suicide vector system; CVD 103-HgR2 was found to colonise infant mice as efficiently as CVD 103. Strain CVD 103-UR, in which sequences encoding urease were inserted using a suicide vector, also colonised infant mice as well as CVD 103. The genetically marked strains CVD 103-HgR, CVD 103-HgR2 and CVD 103-UR form the basis for a generation of defined oral vaccines that may give single-dose, long-lasting protection to populations at risk from cholera. PMID- 8359677 TI - A transformant of Aspergillus fumigatus deficient in the antigenic cytotoxin ASPFI. AB - The aspfI gene encoding a ribonucleotoxin, a putative virulence factor of Aspergillus fumigatus, was inactivated by gene disruption. Gene replacement through homologous recombination by the disrupted allele tagged by the hygromycin B resistance marker was performed by transformation of a pathogenic strain. One transformant with the disrupted aspfI gene failed to produce the ASPFI protein and was shown to be pathogenic for mice. We concluded that this ribotoxin is not a main factor in the colonization of the lung tissues by A. fumigatus. PMID- 8359679 TI - A kinetic study on the regeneration of Candida albicans protoplasts in the presence of cell wall synthesis inhibitors. AB - Aculeacin A and papulacandin B block cell wall regeneration in Candida albicans protoplasts at an intermediate step in which the protoplasts have not yet synthesized the rigid structure of the cell wall and are therefore still osmotically sensitive. In the presence of the antibiotics, total synthesis of glucan is not significantly lowered with respect to control cells, although most of it appears either in the culture medium or in the regenerating wall as alkali soluble glucan. Thus, it is proposed that echinocandins (such as aculeacin A) and papulacandins may not inhibit glucan synthesis per se but instead inhibit its incorporation into the supramolecular organization of the cell wall. PMID- 8359678 TI - Structural features of a polygalacturonase gene cloned from Aspergillus oryzae KBN616. AB - A genomic gene encoding a polygalacturonase from Aspergillus oryzae, used in soy sauce production, was cloned and sequenced. The structural gene comprises 1227 bp coding for 363 amino acids with a putative prepropeptide of 28 amino acids and the open reading frame is disrupted by two short introns of 57 bp and 81 bp. The deduced amino acid sequence of the mature protein showed 63, 63, 63 and 64% homology with those of Aspergillus niger polygalacturonase I, Aspergillus niger polygalacturonase II, Aspergillus tubingensis polygalacturonase II and Cochliobolus carbonum polygalacturonase, respectively. There is, however, little homology among fungal, plant and bacterial polygalacturonases. PMID- 8359680 TI - Prevalence of a Vibrio cholerae 18-kDa antigen in vibrios. AB - An 18-kDa protein that occurs in Vibrio cholerae has been described as an in vivo and low-iron regulated outer membrane antigen. Monoclonal antibodies which recognized this antigen were protective as passive vaccines in the infant rabbit model of cholera disease. In this study, those monoclonal antibodies were used in three immunological assays for surveillance of various bacteria for the 18-kDa antigen. ELISA, and Western blot assays gave variable results with bacteria or outer membrane preparations. The biodot assay was the most sensitive test, detecting the 18-kDa antigen in 29 of 29 V. cholerae strains, independent of biotype or serotype. A few other Gram-negative bacteria and V. parahaemolyticus reacted weakly with our antibodies and antiserum. PMID- 8359681 TI - Expression of the exoglucanase gene in yeast and hyphal forms of Candida albicans. AB - The gene for the beta-(1,3) exoglucanase of Candida albicans was used as a probe to detect transcripts of related genes in C. albicans and in several other Candida species. A single homologous transcript was detected in all of the species tested. Expression of the exoglucanase gene in C. albicans was found to be coincident with the onset of growth and the levels of the transcript were proportional to the growth rate. Comparable levels of the transcript were produced during yeast and hyphal forms of growth. PMID- 8359682 TI - Nucleotide sequence analysis and heterologous expression of the Erysipelothrix rhusiopathiae dnaJ gene. AB - DNA sequence analysis of chromosomal DNA from the Gram-positive facultative intracellular pathogen, Erysipelothrix rhusiopathiae has identified a dnaJ heat shock gene homolog. A 1109-bp open reading frame encoding dnaJ is located immediately 3' to the E. rhusiopathiae dnaK gene. The deduced DnaJ amino acid sequence exhibits the modular structure of other members of the DnaJ protein class including a glycine-rich region and the repeating consensus sequence CXXCXGXGX. Heterologous expression of the dnaJ sequence in Escherichia coli resulted in accumulation of a unique 38.9-kDa protein with an isoelectric point of 8.0. Deletion analysis of the dnaJ gene was used to confirm that the overproduced protein was encoded by the dnaJ sequence. PMID- 8359683 TI - Comparison of barley malt alpha-amylase isozymes 1 and 2: construction of cDNA hybrids by in vivo recombination and their expression in yeast. AB - Germinating barley produces two alpha-amylase isozymes, AMY1 and AMY2, having 80% amino acid (aa) sequence identity and differing with respect to a number of functional properties. Recombinant AMY1 (re-AMY1) and AMY2 (re-AMY2) are produced in yeast, but whereas all re-AMY1 is secreted, re-AMY2 accumulates within the cell and only traces are secreted. Expression of AMY1::AMY2 hybrid cDNAs may provide a means of understanding the difference in secretion efficiency between the two isozymes. Here, the efficient homologous recombination system of the yeast, Saccharomyces cerevisiae, was used to generate hybrids of barley AMY with the N-terminal portion derived from AMY1, including the signal peptide (SP), and the C-terminal portion from AMY2. Hybrid cDNAs were thus generated that encode either the SP alone, or the SP followed by the N-terminal 21, 26, 53, 67 or 90 aa from AMY1 and the complementary C-terminal sequences from AMY2. Larger amounts of re-AMY are secreted by hybrids containing, in addition to the SP, 53 or more aa of AMY1. In contrast, only traces of re-AMY are secreted for hybrids having 26 or fewer aa of AMY1. In this case, re-AMY hybrid accumulates intracellularly. Transformants secreting hybrid enzymes also accumulated some re-AMY within the cell. The AMY1 SP, therefore, does not ensure re-AMY2 secretion and a certain portion of the N-terminal sequence of AMY1 is required for secretion of a re AMY1::AMY2 hybrid. PMID- 8359684 TI - Isolation and characterization of the chicken cystatin-encoding gene: mapping transcription start point and polyadenylation sites. AB - A 6.9-kb fragment containing coding sequences for chicken egg white cystatin (CsnEW) was isolated from a chicken genomic library using the CsnEW cDNA as a probe. The gene is approximately 2.4 kb in length; it contains three exons, two introns and two polyadenylation signals. The exon-intron arrangement corresponds exactly with those of other members of the Csn superfamily. The sequence of the 5' flanking region contains two SP1-binding sites and a high G+C content suggestive of a housekeeping gene. All tissues studied express CsnEW mRNA; Northern analysis showed that CsnEW mRNA levels are most abundant in lung and least abundant in liver and spleen. Mapping of the 3' end of the CsnEW mRNA isolated from brain tissue resolved two CsnEW mRNA species. The larger transcript resulting from the use of the second polyadenylation signal was more abundant than the smaller transcript. Determination of the transcription start point (tsp) of CsnEW mRNA by primer extension and RNase protection assays showed that CsnEW mRNA from a number of chicken tissues was approximately 40-50 nucleotides shorter than that predicted from the CsnEW cDNA isolated from chicken oviduct. PMID- 8359685 TI - Structure determination and evolution of the chicken cDNA and gene encoding prepropancreatic polypeptide. AB - We have previously demonstrated that the C-terminal regions of the rat and human pancreatic polypeptide (PPP) precursors exhibit a high degree of divergence, whereas the N-terminal regions are highly conserved. This blend of structural conservation and divergence in the precursors appears to be caused by splice junction sliding and translational frameshift in the 3'-region of the PPP gene [Yonekura et al., J. Biol. Chem. 263 (1988) 2990-2997]. In the present study, we determined the nucleotide (nt) sequences of the chicken PPP (cPPP) cDNA and gene, and compared them with those of the mammals. In cPPP, the C-terminal region of the precursor is quite heterologous with respect to the rat (rPPP) and human (hPPP) precursors, and this heterogeneity is accentuated by the large deletion in exon 3 of cPPP. Furthermore, mutational accumulation during evolution caused the structural organization of the 3'-region of cPPP to change; cPPP is terminated in exon 3, whereas rPPP and hPPP are terminated in exon 4. Thus, our previous observation regarding the possibility of 'mosaic evolution' [Yamamoto et al., J. Biol. Chem. 261 (1986) 6156-6159] of PPP has been extended and confirmed by this study. Available evidence suggests that 'mosaic evolution' is a phenomenon unique to PPP, and not to the genes encoding the other members of the PPP family, neuropeptide-Y and peptide-YY. PMID- 8359686 TI - Isolation and characterization of the genes encoding mouse and human type-5 acid phosphatase. AB - The gene (mT5AP) encoding murine type-5 acid phosphatase has been isolated and completely sequenced while the gene (hT5AP) encoding human T5AP has been partly sequenced. The murine gene spans 4 kb and contains five exons. Exon 1 is completely non-coding and exon 2 starts with the initiation codon in both mT5AP and hT5AP. The positions of the intron/exon boundaries are completely conserved between mT5AP and hT5AP, but are distinct from the gene encoding the related porcine protein, uteroferrin (Utf). There is strong homology at both the nucleotide (nt) and amino acid (aa) levels between the inferred mouse cDNA and the sequences of rat T5AP and hT5AP, and pig Utf. The mT5AP and hT5AP genes were found to have multiple transcription start points (tsp) by primer extension analysis, consistent with the absence of a consensus TATA box. The sequences for the 5'-flanking regions of mT5AP and hT5AP were determined to -1.6 and -1.0 kb, respectively, relative to the tsp. A 2-kb segment of the mT5AP 5' flanking region linked to a luciferase-encoding reporter gene (Luc) was sufficient to direct tissue-specific transcription in the mouse macrophage cell line, RAW264. Significant sequence similarity between the mT5AP and hT5AP promoters is restricted to the most proximal 200 bp, which also resembles the porcine Utf gene, and a 300-bp segment 700 bp upstream. A progesterone-response element is present only in the mouse promoter and the estrogen- and iron-response elements described previously in the pig gene are absent from both the mouse and human genes. These differences may result in distinctive regulation of T5AP and Utf expression. PMID- 8359687 TI - Sequence of a cDNA encoding the beta 4 subunit of murine integrin. AB - A cDNA coding for the beta 4 subunit of murine integrin (m beta 4) has been cloned and sequenced using mRNA from a murine lung carcinoma as the template. The 5' sequence contains two AUG codons, the second of which initiates synthesis of the mature protein. The cDNA sequence has an open reading frame coding for 1748 amino acids (aa), including a signal peptide, cysteine-rich region, serine- and threonine-rich region, transmembrane domain, and a cytoplasmic domain of over 1000 aa. Overall, the deduced m beta 4 aa sequence has 88% identity with the human beta 4 subunit (h beta 4) sequence deduced from the sequence of placental mRNA. Reverse transcriptase-polymerase chain reaction using primers flanking splice sites for two variant forms of h beta 4 transcripts provided evidence for alternate splicing of RNA in the murine spleen and to a lesser extent in the skin, uterus, and thymus but was found at only one of the two alternative sites. Five potential glycosylation sites present in the extracellular domain of h beta 4 are conserved in m beta 4. One tyrosine in the terminal region of the cytoplasmic domain (position 1600) is conserved between m beta 4 and h beta 4 and has the consensus sequence for tyrosine phosphorylation. Finally, a genomic restriction map of m beta 4 shows that the gene is about 40 kb in length. No restriction-fragment length polymorphisms were detected between BALB/c liver and BALB/c lung carcinoma DNA. PMID- 8359689 TI - Partial characterization of a novel 'GGA' factor which binds to the osteonectin promoter in bovine bone cells. AB - Osteonectin (On)/SPARC (secreted protein, acidic and rich in cysteine) is a highly conserved extracellular matrix protein found in bone and other tissues throughout vertebrate evolution. In previous studies, approximately 500 bp of DNA 5' to the transcription start point (tsp) and a part of exon 1, including homopurine (Rn)/homopyrimidine (Yn)-rich sequences (the 'GGA box' and its complements), was demonstrated to be important in upregulation of On gene expression in a cell-specific manner. The purpose of this study was to decipher the transcriptional regulation of On through its cis- and trans-acting elements. DNase I footprinting analysis indicated protein binding which may be related to the transcriptional factors, AP2, SP1 and a novel 'GGA' factor which binds to the 3' end of the promoter (-286 to +43 to the tsp). Comparisons of footprinting between nuclear extracts of bone (On-expressing) cells and Madin and Darby bovine kidney (MDBK) (nonexpressing) cells indicate that 'GGA' factor binding to a purine GGGGA/GGA-rich sequence is cell-type specific and therefore may be involved in the cell-specific expression of this gene. From ultraviolet (UV) crosslinking experiments, this 'GGA' factor was demonstrated to be a single 40 kDa protein. PMID- 8359688 TI - Transcriptional regulation of the gene encoding cholesterol 7 alpha-hydroxylase in the rat. AB - The cytochrome P450 enzyme, cholesterol 7 alpha-hydroxylase (CYP7A), catalyses the first and rate-limiting step in the conversion of cholesterol to bile acids. Expression of the CYP7A gene is under complex physiological control, encompassing amongst others a feedback down-regulation by bile acids. Using the CYP7A cDNA of the rat as a probe, we isolated a rat genomic clone containing the 5' part of the gene, including approximately 3.6 kb of upstream sequences. Sequence analysis revealed the presence of several putative regulatory elements. Transient expression analyses of transfected primary hepatocytes demonstrated that the major transcription-activating region is located in the proximal 145 nucleotide (nt). Upon addition of taurocholate to the culture, a significant reduction of the transcriptional activity was observed, suggesting the presence of a bile acid responsive element in the proximal region of the CYP7A promoter. In addition, evidence was obtained for the presence of a thyroxine-responsive site further upstream. After addition of taurocholate, steady-state CYP7A mRNA levels, as judged by Northern analysis of hepatocyte RNA, are eightfold reduced. On the other hand, the transcriptional activity of CYP7A, as shown both in CAT assays and run-on experiments, revealed only a threefold decrease. These experiments suggest that both transcriptional control and regulation of CYP7A mRNA stability play an important part in the feedback regulation of CYP7A activity in the rat. PMID- 8359690 TI - An engineered PGK promoter and lac operator-repressor system for the regulation of gene expression in mammalian cells. AB - Previous reports have demonstrated that the Escherichia coli lac repressor can operate effectively in mammalian cells to repress expression of genes driven by modified viral or metallothionein (MT) promoters. We have developed a more general expression system using the promoter from the PGK1 gene (encoding murine 3-phosphoglycerate kinase) which is widely expressed in almost all cell types, including early embryonic and ES (embryonic stem) cells. Firstly, we engineered the lac repressor to include a nuclear localisation signal and placed it under control of the PGK1 promoter. Efficient nuclear localisation of the repressor was demonstrated by mobility-shift assays and immunofluorescence detection. For the target vectors, we modified the wild-type (wt) PGK1 promoter to include lac operator (lacO) sites for binding of the lac repressor and compared a number of different lacO positions and arrangements based on proximity to the native start points for transcription (tsp) and translation. In the absence of repressor, we observed reduced expression of the neo reporter gene for some placements of the lacO, but wt expression for placements near the tsp. When both target and repressor were present in the cells, we observed that the expression of neo could be strongly suppressed and reversibly regulated by induction with IPTG. In particular, for a promoter which contained two spaced lacO replacing native sequence around the major tsp, we observed 90-95% repression by the lac repressor for the neo reporter gene and up to 98% repression for the cat reporter gene. Efficient derepression by IPTG was observed in both cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359691 TI - The Aspergillus niger carbon catabolite repressor encoding gene, creA. AB - In order to undertake a comparative analysis of carbon catabolite repression in two Aspergillus species, the creA gene has been isolated from A. niger by cross hybridization, using the cloned A. nidulans gene. The A. niger gene has been shown to be functional in A. nidulans by heterologous complementation of the creA204 mutation of A. nidulans. Overall, the genes show 90% sequence similarity (82% identity) at the amino acid (aa) level. There were some striking similarities between the aa sequences encoded by the two fungal creA genes and two genes involved in carbon catabolite repression in Saccharomyces cerevisiae. The zinc-finger regions showed 96% similarity (84% identity) with the zinc-finger region of the MIG1 gene of S. cerevisiae. The CREA protein contains a stretch of 42 aa that is identical in A. niger and A. nidulans, and these show 81% similarity (33% identity) with a region of the S. cerevisiae RGR1 gene. PMID- 8359692 TI - The 59-kDa polypeptide constituent of 8-10-nm cytoplasmic filaments in Neurospora crassa is a pyruvate decarboxylase. AB - The fungus Neurospora crassa harbors large amounts of cytoplasmic filaments which are homopolymers of a 59-kDa polypeptide (P59Nc). We have used molecular cloning, sequencing and enzyme activity measurement strategies to demonstrate that these filaments are made of pyruvate decarboxylase (PDC, EC 4.1.1.1), which is the key enzyme in the glycolytic-fermentative pathway of ethanol production in fungi, and in certain plants and bacteria. Immunofluorescence analyses of 8-10-nm filaments, as well as quantitative Northern blot studies of P59Nc mRNA and measurements of PDC activity, showed that the presence and abundance of PDC filaments depends on the metabolic growth conditions of the cells. These findings may be of relevance to the biology of ethanol production by fungi, and may shed light on the nature and variable presence of filament bundles described in fungal cells. PMID- 8359693 TI - Functional domains of the transcriptional activator NUC-1 in Neurospora crassa. AB - The NUC-1 regulatory protein directly controls the transcription of these genes and how the activity enzymes in Neurospora crassa. To understand how NUC-1 regulates the transcription of these genes and how the activity of NUC-1 is modulated by other regulatory proteins, two putative functional domains of NUC-1 were analysed: the DNA-binding domain and the regulatory domain. The DNA-binding activity of NUC-1 has not been directly demonstrated; however, results of deletion analysis, sequence analysis of the nuc-1 mutant alleles, and strong sequence similarity with the Saccharomyces cerevisiae PHO4 protein strongly suggest that the basic helix-loop-helix motif of NUC-1 forms a DNA-binding domain. Deletion and mutant analyses revealed that 39 amino acid (aa) residues (aa 463 to 501), or fewer, of NUC-1 are interacting with the negative regulatory factor(s), the PREG and/or PGOV proteins. PMID- 8359694 TI - Characterization of the pyruvate kinase-encoding gene (pki1) of Trichoderma reesei. AB - The pyruvate kinase-encoding gene (pki1) from Trichoderma reesei was isolated by hybridization to the corresponding Aspergillus nidulans pkiA gene. The 1614-bp nucleotide (nt) sequence of the cloned gene codes for a 538-amino-acid protein. The coding sequence contains a single intron of 246 nt at a position identical to that of intron E in the A. nidulans gene. The PKI protein shows extensive homology to the PKIs of A. nidulans and A. niger (67%) and Saccharomyces cerevisiae (59%). The 5' non-coding sequence contains a number of motifs typical for yeast glycolytic genes, but so far only rarely found in filamentous fungi. PMID- 8359695 TI - Functional analysis of chicken vimentin distal promoter regions in cultured lens cells. AB - Synthesis of the cytoskeletal intermediate filament protein vimentin (Vim) in the lens is unexpected due to the mesenchymal preference of Vim-encoding gene (Vim) expression and the epithelial origin of the lens. Previous studies indicated that chicken Vim gene expression in cultured lens cells is regulated by both positive- and negative-acting sequence elements within the first -767 nucleotides (nt) of its promoter. Here, we demonstrate the existence of additional upstream chicken Vim promoter elements which function in transfected lens cells. Sequences within the nt -1360/-1156 region repressed promoter activity in transfected lens cells to levels lower than that observed for the previously defined more proximal repressor elements. The -1612/-1360 region activated promoter activity to levels similar to those observed for the strongest previously defined proximal promoter. The nt sequence analysis of the upstream promoter region revealed the presence of multiple consensus repressor and activator transcription-factor-binding sites. Several of these sites have been implicated for lens expression of enzyme crystallin-encoding genes (cry), suggesting that Vim expression may share features with the cry genes for recruitment and high-level expression in the lens. PMID- 8359696 TI - Transcription factor IID probes localize a single gene to the proximal region of mouse chromosome 17. AB - We have used a 5' fragment of the gene GTF2D, which encodes human transcription factor IID, and Chinese hamster-mouse somatic cell hybrids to map the murine homologue, Gtf2d, to a single locus on mouse chromosome 17 (Chr 17). Linkage analysis of progeny from an interspecific backcross localized the gene near the marker D17Leh66 in the proximal region of Chr 17. PMID- 8359697 TI - Sequence analysis of mouse cDNAs encoding ribosomal proteins L12 and L18. AB - Mouse cDNAs encoding ribosomal proteins (r-proteins), L12 and L18, were isolated and their sequences determined. The L12 cDNA was found to contain 639 bp, including a coding sequence of 498 nucleotides (nt), 5' (78 nt) and 3' (45 nt) untranslated regions (UTRs), and a poly(A) tail of 18 nt. The L18 cDNA was shown to consist of 648 bp, including a coding sequence of 567 nt, 5' (26 nt) and 3' (39 nt) UTRs, and a poly(A) tail of 16 nt. The nt sequences of the protein-coding region from the mouse L12 and L18 cDNAs were found to exhibit 96% and 92% identity, respectively, with those of the rat. With the use of mouse L12 and L18 cDNA probes, multiple (at least 10) copies of the L12 and L18 gene families were shown to be present in the mouse and rat genomes. However, there was no sequence heterogeneity detected among seven L18 cDNA clones, indicating that only one copy of the L18 gene-related sequences is functional, and the other copies are presumably nonfunctional pseudogenes. The complete amino acid (aa) sequences of the mouse r-proteins, L12 and L18, were deduced from the nt sequences of their cDNA clones. L12 has 165 aa and a M(r) of 17,790, while L18 has 188 aa and a M(r) of 21,570. The aa sequences of the mouse r-proteins, L12 and L18, exhibit 98% and 94% identity, respectively, to those of rat. PMID- 8359698 TI - cDNA cloning and mRNA expression of calponin and SM22 in rat aorta smooth muscle cells. AB - We cloned and sequenced cDNAs encoding calponin (Calp) and SM22 (smooth muscle specific 22-kDa protein) from rat aorta (RaA) smooth muscle (Smu) cells. The 1504 bp calp cDNA contains a single open reading frame (ORF) which encodes 297 amino acids (aa) (M(r) 33,342). The 1186-bp SM22 cDNA contains a single ORF which encodes 201 aa (M(r) 22,601). There were 43% identical aa in a 181-aa overlap between RaA Calp and SM22. Especially for the C-terminal region of SM22 and for the first repeat motif of Calp, 70% identity was observed. Northern blot analysis revealed that the calp and SM22 mRNAs were expressed in RaA Smu, but not in rat cardiac and skeletal muscles. SM22 mRNA was much more abundant than calp mRNA in RaA (3- to 4-fold). The expression levels of the calp and SM22 mRNAs in RaA showed a significant increase for 5 to 15 week old rats (1.5- to 3-fold) with vascular development and blood pressure elevation. No significant differences were observed in the expression of the RaA calp and SM22 mRNAs between normotensive (Wistar Kyoto) and spontaneously hypertensive rats (SHR). PMID- 8359699 TI - Cloning and sequencing of the cDNA encoding a mouse IL-2 receptor gamma. AB - A mouse cDNA encoding an interleukin-2 receptor gamma (mIL-2R gamma) was cloned. The primary amino acid sequence deduced from the nucleotide sequence exhibits 70% overall similarity with human IL-2R gamma and, in particular, the predicted cytoplasmic region shows a higher degree of similarity (about 84.7%). PMID- 8359701 TI - [Profile of Prof. emeritus M.C. Alfonso Alvarez Bravo]. PMID- 8359700 TI - Sequence of a cDNA encoding dog insulin-like growth factor I. AB - Polymerase chain reaction amplification of a cDNA derived from dog left ventricular myocardium, using primers specific for rat insulin-like growth factor I (IGFI), exons 3 and 6, yielded the dog clone, IGFI5.1. This clone includes the signal peptide sequence, the entire coding sequence for mature dog IGFI and the C terminal extension sequence. By analogy with the organization of the rat and human IGFI genes which encode two extension peptides, we have termed this cDNA, dog IGFIa. The deduced amino acid sequence of mature dog IGFI is identical to that of human IGFI. PMID- 8359702 TI - [Assisted reproduction. Alternatives]. AB - From the first publications about fertilization in vitro (FIVTE) Patrick Steptoe and Robert Edwards, added several knowledges and new concepts in modern Gynecology, so starting a new era of Reproductive Medicine, so ideating a series of programs and methodologies to emulate the physiological ovarian cycle; with this concept Ricardo Asch carries the transference of gametes to tubes and calling this procedure GIFT. These methodologies with a high technology have been called Assisted Reproduction, which is reviewed in this paper. PMID- 8359703 TI - [Vaginal intraepithelial carcinoma. Diagnosis and management]. AB - At the Colposcopy Clinic, Hospital "Luis Castelazo Ayala", from January 1990 to May, 1991, 24 cases of vaginal intraepithelial neoplasia, were diagnosed. The average age of the patients was 54.2 years. Twenty had antecedents of previous hysterectomy; seven (29%) with benign pathology, and twelve (50%) with malignant pathology. Only four patients (17%) presented with symptomatology. In all the cases it was suspected by abnormal cytology. Colposcopy was done, as well as directed biopsy, finding that the pointillism and white epithelium, were the most frequent findings, with localization mainly in the vaginal cupule and vaginal upper third. Histopathological correlation showed NIVa I in three cases (13%) NIVa II in six cases (25%), and NIVa III in 15 (62%). Treatment was done with cryotherapy in 10 patients; with 5-fluorouracil in eight; cryotherapy plus 5 fluorouracil in three; radiotherapy in two, and it was not done in one. It was found persistent lesion in two cases treated with cryotherapy, and in one case with radiotherapy; there was a complication in one case after cryotherapy (retrovaginal fistula). Vaginal cytology should be done in every patient after hysterectomy, by benign or malignant pathology. In NIVa the colposcopic study is mandatory for the adequate diagnosis. 5-Fluorouracil showed to be an adequate treatment. PMID- 8359704 TI - [Seven-year experience with microsurgery]. AB - From 700 laparoscopies performed, in 600 of them (85.7%) the tuboperitoneal factor was altered. Surgery included: termino-terminal plastia 70 cases (36%), (3 patients had previous plastia); adhensiolysis 62 (31%), salpingostomy 48 (24%), neoimplantation 10 (5%), and mixed surgery 9 (4%). After surgery, desertion was present in 78 patients. Of the 121 remaining, 34 (28.1%) had primary sterility and 87 (71.9%) secondary sterility. 74 patients (61.2%) obtained pregnancy, 62 (83.8%) reached term, seven were abortions of first trimester (9.5%) and were five ectopic pregnancies (6.7%). The interval between surgery and pregnancy achievement was 1 to 48 months, 12.8 months average. We emphasize the 47 patients analysis who didn't has pregnancy, through: remark time after surgery, histerosalpingography, new laparoscopy and reevaluation of sterility factors; the results were: 19 cases (40.5%) have a 5 to 60 months time after surgery, 19.5 months average, 18 (38.3%) had new tubary obstruction, three (6.4%) with endometriosis treatment, three (6.4%) have tuberculosis genital treatment, two (4.2%) with falling again endocrine-ovarian factor, and two (4.2%) with masculine relapse. A decease was present because anesthetic complication. We underline selection surgery criterion and a strictly evaluation, such as an antiadhesion pre, trans and postoperative regime, ligamentopexya of rounds ligaments and a conscious education of the patients in their strictly pursuit. PMID- 8359705 TI - [Effect of L-arginine and polyamines on sperm motility]. AB - The biochemical and physiological relevance of L-arginine is described in the male reproductive system. This amino acid has been used successfully in the treatment of some reproductive diseases. L-arginine is the precursor in the synthesis of putrescine, spermidine and spermine. It has been suggested that these polyamines have important role as initiators in the spermatic motility processes. Some practical uses for L-arginine are proposed. PMID- 8359706 TI - [Perforation of the large intestine caused by a type 7 medicated copper IUD]. AB - A case of large bowel perforation at sigmoides level, secondary to application of a "medicated" intrauterine contraceptive device (IUD), Copper-7, is presented. This variety of IUD translocated to peritoneal cavity may provoke peritoneal or omental adhesions, volvulus, uterocutaneous fistula and bowel perforation, which involves a significant morbidity. The diagnosis is often delayed and difficult to establish, but, once knowing the exact location of ectopic IUD, it is justified the immediate removal from the peritoneal cavity by either laparoscopy or laparotomy with the utilization of prophylactic antimicrobials for colon preparation before elective surgery. PMID- 8359707 TI - Visualization of iron in cultured macrophages: a cytochemical light and electron microscopic study using autometallography. AB - The objective of this study was to develop a sensitive cytochemical method for the visualization of iron, both at light microscopical (LM) and at electron microscopical (EM) levels, in glutaraldehyde-fixed cultured cells with reasonable morphological preservation. The method is based on autometallography (also called the sulfide silver method or the Timm technique). Gold, silver, and various metal sulfides have previously been shown to act as catalysts for cellular silver deposition from a physical developer (autometallography). In our modification of this cytochemistry, a high pH is used during the initial sulfidation step to guarantee adequate levels of sulfide ions to generate enough Fe(II or III) sulfide. Since this procedure may cause severe cellular distortion, we initially stabilize the cultured cells by a glutaraldehyde fixation. We have compared our new high pH, high S2- LM and EM variety of autometallography with other modifications of this technique that have previously been used for LM and EM demonstration of easily sulfidated heavy metals, such as zinc. Cultured mouse macrophages were examined for the localization of reactive metals following endocytosis of ferritin or inorganic Fe(III) iron. Ag-precipitates, presumed to indicate the presence of iron, were predominantly found within secondary lysosomes of the acidic vacuolar apparatus. The relation of the Ag-precipitates to iron was proven by the fact that iron-exposed cells showed a much reduced amount of silver precipitates after subsequent exposure to deferoxamine a potent iron chelator. Moreover, control macrophages neither exposed to iron nor to ferritin showed only a low normal lysosomal content--and a few extralysosomal sites--of reactive substances, believed to be iron. PMID- 8359708 TI - Effects of reactive oxygen species on arachidonic acid metabolism in rabbit platelets. AB - Rabbit platelets were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane (TX) B2, and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) from exogenous arachidonic acid. Xanthine plus xanthine oxidase suppressed the production of 12 HETE, TXB2, and HHT by 65-69%. This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase, mannitol, or dimethylsulfoxide, indicating that H2O2 is the responsible metabolite. These results suggest that H2O2 plays an important role in the regulation of platelet cyclo-oxygenase and lipoxygenase activities. PMID- 8359709 TI - Inhibition of lipoxygenase and cyclooxygenase augments cardiac injury by H2O2. AB - The role of arachidonic acid metabolites in the cardiac effects of toxic oxygen metabolites (TOM) was investigated in buffer-perfused rat hearts (Langendorff model). Hydrogen peroxide (H2O2, 200 microM) was given for 10 min to generate TOM, followed by 30 min recovery. H2O2 reduced left ventricular developed pressure (LVDP), increased left ventricular end-diastolic pressure (LVEDP), and increased coronary flow (CF). The hydroxyl radical scavenger thiourea inhibited the H2O2-induced effects. Perfusion with three lipoxygenase inhibitors, AA861, BWA4C, and diethylcarbamazine, in addition to H2O2, augmented the decrease of LVDP and the increase of LVEDP induced by H2O2. The cyclooxygenase inhibitor indomethacin had the same effects. The H2O2-induced increase in CF was not influenced by diethylcarbamazine, but inhibited by all other drugs. Control perfusion with drugs alone did not influence cardiac function. In conclusion, inhibition of lipoxygenase and cyclooxygenase augmented the depression of cardiac function induced by TOM. Leukotrienes and prostanoids appear to be protective against H2O2-induced cardiac injury. PMID- 8359710 TI - Ferrous-iron-induced oxidation in chicken liver slices as measured by hemichrome formation and thiobarbituric acid-reactive substances: effects of dietary vitamin E and beta-carotene. AB - Hemichrome formation in chicken liver slices was determined by employing a Heme Protein Spectra Analysis Program (HPSAP) on the visible spectrum of the liver tissue. Relative hemichrome formation (RHF) in liver tissue exposed to ferrous iron for 1 h at 37 degrees C could be predicted according to the general catalytic equation RHF = k.[Fe2+]/(Ap + [Fe2+]), with k = 132 +/- 30, where the factor Ap represents the additive antioxidative potential in the liver tissue. RHF in Fe2+ exposed liver slices incubated at 37 degrees C for 1 h correlated significantly with formation of thiobarbituric acid-reactive substances (TBARS) (r = .77, P < .0001). RHF was found to decrease significantly with increasing vitamin E concentration in liver tissue exposed to ferrous iron (1 h, 37 degrees C). However, the influence of beta-carotene on RHF in ferrous-iron exposed liver slices (1 h, 37 degrees C) was less evident, as the concentration of Fe2+ was found to be decisive for whether beta-carotene acted as an antioxidant or a prooxidant under the conditions in question. Results in the liver slice model system regarding the effect of vitamin E and beta-carotene on iron overload were supported in a subsequent in vivo iron injection experiment with chicks. These observations indicate that RHF is a sensitive marker for ferrous-iron-induced oxidative damage in the present tissue slice system. PMID- 8359711 TI - Increased generation of reactive oxygen species in embryos cultured in vitro. AB - Previous studies have suggested that oxygen toxicity is closely related to the developmental blockage of embryos cultured in vitro. In this study, to obtain an actual proof of the increase in production of reactive oxygen species within embryos, we have measured the level of H2O2 in individual embryos using a fluorimetric method. Mouse (ICR) pronuclear stage embryos from the oviducts were cultured for a specified time under various conditions in a medium to which 2',7' dichlorodihydrofluorescin diacetate was added. After washing the embryos, the fluorescence emissions of the H2O2-dependent oxidative product in embryos were measured. The fluorescent emissions were lowest in embryos cultured under 5% O2 and highest under 40% O2 (5% < 20% < 40%), just the inverse of the culture efficacy. The fluorescence emmissions of embryos cultured in Ham's F-10, which contains hypoxanthine and transition metals such as Cu and Fe, were higher than those cultured in BWW and alpha MEM, which do not contain these components (alpha MEM < BWW < Ham's F-10; again this is the inverse of the culture efficacy). The fluorescence emissions of embryos increased with the time of the exposure to visible light. L-cysteine and thioredoxin, both of which have been shown to promote embryo development, decreased the fluorescence emissions of embryos. All of these results would provide direct evidence for the hypothesis that oxygen radicals are involved in the developmental blockage. PMID- 8359712 TI - Current status of antioxidant therapy. AB - There is evidence that free radical damage contributes to the aetiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. In this review we are not concerned with tissue damage in vivo induced directly by radicals from exogenous sources, such as air pollutants and tobacco smoke, high-pressure oxygen, irradiation, or through the metabolism of certain solvents, drugs, and pesticides. Rather, we address some of the disease states associated with increased oxidative stress from endogenous sources and the possible therapeutic advantage of the antioxidant treatment. This raises the question of the antioxidant status of individuals and its role in protection against amplification of certain disease processes. We have chosen to concentrate mainly on coronary heart disease, reperfusion injury, and organ storage for transplantation. PMID- 8359713 TI - Alterations in free radical scavenging mechanisms following blood-brain barrier disruption. AB - It has been reported earlier that rat microvessels which constitute the blood brain barrier (BBB) are rich in free radical scavenging enzymes. In the present investigation, BBB of rat was disrupted by intravenous infusion of the hypertonic saline and changes in enzymes--namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR)--were evaluated in the brain microvessels at 30 min after the intravenous administration of hypertonic saline, being the time of peak effect. There was a significant increase in the activities of CAT (40%), GPx (26%), and SOD (16%) over the control values. In addition, within 90 min BBB was found to be reestablished and the levels of enzymes reverted to normal. Malondialdehyde (MDA) levels and activity of lactate dehydrogenase (LDH) remained unaltered during and following disruption, suggesting that there was no change in the membrane lipid environment. Similarly, there was no cell lysis. The results suggest that the disruption of BBB following hypertonic saline administration might be due to an increase in the generation of free radicals in the brain microvessels. PMID- 8359714 TI - [Promotion program for breast feeding in Poland. II. Analysis of the breast feeding situation in Poland]. AB - Assessment of breast-feeding situation in Poland was based on three kinds of nation-wide surveys conducted in 1988: newborn feeding and breast feeding routines in maternity wards epidemiology of breast-feeding and other feeding methods in first six months of infant life KAP study among MCH professionals The major findings of the surveys were: conflicting with lactation maternity wards routines especially: very initiation of breast-feeding, administration of liquids and formulas, rigid feeding schedule, separation of newborns from the mothers too early supplantation of breast-feeding lack of current breast-feeding knowledge among MCH professionals. PMID- 8359715 TI - [Accuracy of pretherapeutic diagnosis of early invasive cervical carcinoma]. AB - In 114 women treated at the First Department of Gynecology Medical Academy in Cracow, between the years 1967-1985 there was compared the agreement of the histological examination of a colposcopy directed biopsy specimen with the histological examination of the operative specimen in cervical carcinoma with early invasion. In 103 cases (90.4%) histological examination of a guided biopsy specimen of early invasive carcinoma confirmed the results of the operative specimen. In 1 case the operative specimen confirmed severe dysplasia as in the guided biopsy specimen early invasive carcinoma. In 10 cases the guided biopsy specimen confirmed CIN 3 (6 cases severe dysplasia and 4 cases ca in situ), the results of operative specimen confirmed early invasive carcinoma. In 5 out the above 10 cases, the results were altered due to a 3-8 mouth delay of surgery. The divergence regards to the remaining 5 cases (4.4%). This high agreement of histological examination of a colposcopy guided biopsy specimen and operative specimen shows a significant accurate meaning of colposcopy in confirming early lesions of cervical carcinoma. PMID- 8359716 TI - [Removal of melanocytic nevi as a prophylaxis and early recognition of cutaneous and mucous malignant melanoma]. AB - In article 1240 melanocytic nevi were described in which 26 melanomas were found. The authors present necessity of early removal (excision) of dysplastic melanocytic nevi, pigmented lesions with high risk of malignant transformation, giant congenital melanocytic nevi before adolescence and nevi which are irritated constantly. Particularly dysplastic nevi and pigmented lesions with high risk often contain melanoma "in situ" or invasive melanoma. Such a procedure early done, prevents developing of tumor and makes possible early recognition of melanoma but the procedure depends on a conscience of patients, members of their families, nurses and doctors. PMID- 8359717 TI - [Use of nalador for pregnancy termination in the second trimester]. AB - The efficacy of Nalador in the induction of second trimester pregnancy termination in 23 pregnant women was assessed. The most frequent indications for pregnancy termination were: severe CNS malformations, chromosome aberrations, hydatidiform mole and missed abortion. In all treated cases Nalador was effective. There was no correlation between a total dose of Nalador needed for pregnancy termination and gestational age. The total dose of drug was not correlated with the indication to pregnancy termination. The important side effects were not observed. Neither in red and white blood cell patterns nor in blood clotting significant changes were found. The genital tract and uterine injury were not observed (in one case Nalador was administered to the patient who underwent caesarean section in the past). It has been concluded, that Nalador is effective, safe and free of side effects for the induction of the second trimester pregnancy termination. PMID- 8359718 TI - [Selected indices in perinatal evaluation of the newborn with respiratory disturbances. I. Usefulness in differential diagnosis]. AB - There are several maternal and fetal factors, which may influence the development of respiratory disturbances in the newborn. Certain, indices of perinatal evaluation (delivery route, gestational age, birth weight, maturity degree, sex and Apgar score) in two groups of patients were compared. The first group compressed 36 newborns with Hyaline Membrane Disease (HMD), the second called aspiration--pneumonia (AP) group-44 newborns with other kinds of respiratory disturbances: 18 with pneumonia, 12 with fetal liquid aspiration syndrome, 8 with meconium aspiration syndromes and 6 with transient tachypnea. The diagnosis of each kind of respiratory disorder was based on the criteria of Hjalmarson. In both groups high percentage of newborn babies born by cesarean section (higher in AP group) was found. Hence the conclusion that the decision to perform this procedure should consider the risk of neonatal pulmonary complications. In the HMD group lower gestational age was found and in the AP group more babies were born with intrauterine dystrophy. In both groups prevalence of the male sex and low Apgar score was found. PMID- 8359719 TI - [Selected indices in perinatal evaluation of the newborn with respiratory disturbances. II. Prognostic value]. AB - Respiratory disturbances are the most frequent causes of life-threatening situations in the newborn. In this paper evaluation indices of the newborn were compared in 2 groups of patients. The first comprised 36 babies with Hyaline Membrane Disease (HMD) with good or fatal outcome, in the second 44 newborns with Aspiration-Pneumonia (AP) syndromes were included. Prognostic value of following indices was considered: delivery route, gestational age, birth weight, maturity degree, sex and Apgar score. Bad prognostic value of low birth weight was found in the HMD group and low Apgar score and intrauterine dystrophy in the AP group. Mortality was similar in children delivered vaginally and by cesarean section in both groups of patients. PMID- 8359720 TI - [Breast dysplasia in women]. AB - The current knowledge concerning the fibrocystic disease of the breast is presented in this work. The authors outlined the theoretical principles of the problem and the most important diagnostic methods as well as the prophylaxis and prognostic in the fibrocystic disease of the breast. PMID- 8359721 TI - [Risk factors in breast cancer]. AB - This assay analyses the risk factors which have great importance in breast cancer pathogenesis. Having excluded the group of higher risk in women's population we can early detect this disease and treat it as well. It may extremely improve the results of breast cancer treatment. PMID- 8359722 TI - [Occult cervical cancer developing after diagnostic-therapeutic conization of CIN 3]. AB - A case of the so called occult cervical cancer which developed 2 years after the conisation performed in a 45-year old woman on account of CIN 3 has been described. Cancer was detected in the operative specimen of the removed uterus. Hysterectomy was performed on account of the progressive form of the myomas. The multiple colposcopy and cytological follow-up examination after conisation was always negative, just as the histological examination of the tissue specimen of the cervical canal. The hypothetical course of the development of the cancer has been discussed. In connection with the above findings a modification of the conisation technique, especially in older women, is suggested. PMID- 8359723 TI - [Simultaneous ectopic and intrauterine pregnancy]. AB - The case simultaneous intrauterine and ectopic pregnancy was presented. The patient was admitted to the clinic, because of abdominal pain and vaginal bleeding. The curettage was performed and the trophoblastic tissue was removed. Five days later she was operated because of the rupture of the tube caused by ectopic pregnancy. The diagnosis was confirmed by histopathological examination. PMID- 8359724 TI - [Climacteric in the male--reality of fiction?]. PMID- 8359725 TI - [A case of pregnancy with polycystic kidneys]. AB - The authors described a course of pregnancy and delivery of pregnant women who was admitted to the hospital in the third trimester with symptoms of sepsis in course of the pyelonephritis. Signs of a kidney insufficiency and pulmonary oedema were observed. During hospitalization ultrasound examination showed polycystic kidneys. PMID- 8359726 TI - [Twin pregnancy with intrauterine death of one fetus]. AB - A case of twin pregnancy with congenital malformations and intrauterine death of one fetus in the 27th week of pregnancy has been discussed. The pregnancy was continued with special care of the mother and the alive fetus. During all stay of the pregnant in the clinic no coagulation disturbances were observed. In the 33rd week of pregnancy spontaneous labour occurred, which was conducted by vaginal delivery. Simultaneously a macerated dead fetus and an alive premature newborn were born. The alive one was charged home in good condition in the 38th day of staying in the Neonatal Ward. PMID- 8359727 TI - [Promotional program for breast feeding in Poland. III. Proposed organizational implementation]. AB - On the basis of the experience and data gained during breast-feeding situation assessment process (see Part II) the major activities of the breast-feeding promotion programme were identified as follows: 1. Training of health workers which aims the revision and change of practices in health services responsible for mother and child care. 2. Education of population about advantages of breast milk and breast-feeding management. The detailed project of the implementation of the programme on the national scale was presented. PMID- 8359728 TI - [Evolution of a method for breech deliveries during 1946-1990 in material from the 1st Obstetric Clinic of the Medical Academy in Wroclaw]. AB - The analysis of 2191 breech deliveries in the 1st Obstetrics Clinic of Medical Academy in Wroclaw shows that there was a steady increase in the percentage of cesarean sections (from 0.8% in 1946-1955 to 59.6% in 1986-1990) and a decrease in the number of vaginal deliveries, especially manual procedures. The neonates born from cesarean section were generally in better condition than the ones born through vaginal delivery. There were also considerably fewer cases of trauma and perinatal mortality than in the natural delivery group. The greatest trauma and stillbirth rate has been observed in neonates after total extraction and in premature deliveries. PMID- 8359729 TI - [Value of vascular resistance in fetal circulation during normal pregnancy]. AB - The aim of the study is to estimate the values of resistance index (RI) in the arteries of the fetus using color doppler ultrasound. Measurements have been made in aorta, umbilical and medial cerebral artery of the fetus and in arcuate artery of the pregnant women. 50 women have been examined every 4 weeks and another 50 every 6 weeks during normal pregnancy. Resistance index has been calculated based on analyses of flow waves configuration in all of the mentioned arteries. Likeness between curves obtained in women examined every 4 and 6 weeks in obvious. The examination of mean RI values shows that vascular resistance in descending aorta remains constant during the vascular resistance in descending aorta remains constant during the all the period. In arcuate artery vascular resistance falls down until 22 week of pregnancy and then settles on constant level. RI of umbilical artery decreases during pregnancy and in median cerebral artery reaches its peak in 32/34 week of pregnancy. PMID- 8359730 TI - [Evaluation of surfactant administration in neonates with respiratory distress syndrome. III. The role of intra-uterine stimulation on lung maturity]. AB - Prenatal corticosteroids and exogenous surfactant therapy independently reduce the adds of neonatal death by about 40%. It is not clear however if babies who develop RDS despite prenatal corticosteroid therapy behave differently when later given exogenous surfactant. This paper presents an evaluation of the outcome of babies treated with Curosurf (a porcine surfactant) for RDS depending upon whether they received prenatal corticosteroids (16 babies) or not (11 babies). Although not randomised these two groups of babies appear to be similar in respect of gestational age. However, lower mortality was found in the group treated with prenatal corticosteroids (12.5% vs. 27.2%). PMID- 8359731 TI - [Evaluation of ovulation induction in infertile women who are underweight]. AB - The induction of ovulation in 74 underweight normally menstruated sterile women were analyzed with regard to the body mass index (BMI). The underweight patients presented 10.5% of the treated anovulatory women among them 4.8% presented serious weight loss. The concentration of serum gonadotropins and estradiol just before treatment did not allow to anticipate the results of therapy. The interesting observation concerned the cases with low concentration of serum FSH and LH which was more frequently found in nonresponding patients. The ovulatory ratio was not high and was comparable in all groups but pregnancy ratio in the responders was 1.5 times higher in slightly underweight patients. Among the nonresponders more than half of them demonstrated follicular growth confirmed by USC, serum estradiol and mucus viscosity. PMID- 8359732 TI - [Diagnostic value of mucin-like associated antigen (MCA) in neoplasms of the mammary gland]. AB - The aim of the present study was to evaluate the diagnostic value of the new tumour marker MCA in serum from women with breast cancer. Relationship between presence MCA in serum and cER, cPgR, nER, nPgR in aqueous extracts from cancer tissues was subject of our investigation, too. Immunoenzymatic method (Roche) which employed monoclonal antibody MAb b-12 was used for determination of MCA in serum 49 operable patients (preoperative determination). In a group of 26 cancer patients MCA and cER, cPgR, nER, nPgR were tested simultaneously. Steroid hormone receptors were measured by immunoenzymatic method (Abbott). Mean concentration of MCA in women with breast cancer (n = 36) was higher as compared with control (n = 21, p < 0.001). When 6.86 U/ml was took as mean level of MCA in control group it was found that 46% women with benign tumours, 64% with carcinoma ductal and 62% with carcinoma lobular have had concentrations of MCA below this value. Also it was found that differences between mean levels of MCA and cER, cPgR, nER, nPgR were statistical significance only in women with carcinoma ductal. On the basis of our own investigations we can suggest that MCA has limited value in the diagnosis of breast cancer. PMID- 8359733 TI - [Psycho-gynecologic reflections]. PMID- 8359734 TI - [KOMPOR--Computer system for perinatal surveillance. I. System description]. AB - The computer system of perinatal surveillance--KOMPOR-build by OBREAM-TEMED in Zabrze is described. This system enable to collect the personal data of patients, obstetrical anamnesis as well as very precise analysis "on line" of cardiotocographic records. PMID- 8359735 TI - [Unsaturated fatty acids of trans isomers in plasma of pregnant women and birth weight]. AB - Trans unsaturated fatty acid originated from synthetic technology. Human consumption of trans isomers of unsaturated fatty acids increased markedly. The induction of growth failure was observed in animals when trans fatty acids were supplied. We studied whether or not there are indications of untoward effects of trans fatty acids in premature infants. Trans fatty acids were in higher concentrations in plasma of 23 women in pre-term delivery compared with 21 women delivering in normal term. Trans fatty acids in plasma were also inversely correlated to birth weight and with gestational age. These data indicate a impairment of intrauterine growth by trans isomer of unsaturated fatty acids. PMID- 8359736 TI - [Increased activity of aminotransferases (ALAT, AspAT) in pregnant women threatened with immature and premature delivery treated with fenoterol]. AB - 2330 pregnant women were admitted to the 2nd Department of Pregnancy Pathology at the Polish Mother's Memorial Hospital (PMMH) in Lodz, Poland, during the period from 28th March, 1989 to 30th June, 1991. Out of the group 1055 pregnancies were treated because of the risk of premature delivery (45.28%). In five (5) cases a significant rise of ALAT and AspAT aminotransferase activity occurred during fenoterol therapy. Laboratory tests excluded infectious etiology in the rise of the enzymes in question (no markers typical for HBV, HAV infection). Toxic injury of hepatic cells being suspected, fenoterol therapy was withdrawn, followed by a decrease of aminotransferases activity to normal values in those five (5) cases. No increase in the activity of ALAT and AspAT occurred in further follow up of the pregnant women in pregnancy and in puerperium. Since no other hepatotoxic factors appeared, it may be assumed that a chronic administration of fenoterol can cause transient injuries of hepatic cells. For this reason all pregnant women treated with betamimetics require examinations of the liver. PMID- 8359737 TI - [Ultrasonographic evaluation of fetal weight in normal, single fetus pregnancies in the population of Wroclaw]. AB - The aim of this paper was the analysis of the clinical usefulness of the nomogram presented by Hansmann for the fetal weight prediction in normal, single fetus pregnancies of Wroclaw population. The authors proved, that in the group of 36 pregnant women the least difference between fetal weight evaluated before birth and the birth weight of newborn was noted in the group of babies with birth weight 2000-4000 g. In the group with birth weight below 2000 g and over 4000 g respectively, the twice to octuple evaluation error is expected. PMID- 8359738 TI - [Ultrasonographic evaluation of growth in twin pregnancies in the population of Wroclaw. I]. AB - Authors have ultrasonographically evaluated and analysed appropriate parameters determining fetal growth in bigeminal pregnancies in the population of Wroclaw. The following parameters were taking in consideration: biparietal head dimension (BPD), transversal chest dimension (THD) and thigh bone length (FL). After the comparative analysis of the average BPD, THD, and FL values in fetuses from 28 40th single fetus and bigeminal pregnancies authors revealed, that BPD and TDH values were significantly smaller in twins that single fetuses. No correlation was found in FL values in both groups. In the aim to obtain more accurate evaluation of intrauterine growth in twins. Authors proposed an application of special ultrasonographic BPD and THD parameters net-works, different from those applicable for primiparous pregnancies. PMID- 8359739 TI - [Ultrasonic evaluation of fetal growth of twins in the Wroclaw population. II. Proposed percentile curves of ultrasonographic parameters]. AB - Authors analyzed and evaluated biparietal head dimension (BPD), transversal chest dimension (THD) and femur length (FL) measured in the fetuses from 28 to 40th week in bigeminal pregnancies on the material of Wroclaw population. Obtained results were presented as percentile curves of each parameter in succeeding weeks of pregnancy. In the face of findings in the 1st part of work (statistically lower parameters BPD and THD in twins in confrontation with fetuses in single fetus pregnancies and lack of correlations between FL dimensions), authors are of opinion that, for accurate evaluation of twins growth in examined population, in the period from 28 to 40 weeks of pregnancy, the application of ultrasonographical parameters net-work of BPD and THD parameters in necessary. Moreover, the authors are considering that the presented percentile BPD and THD curves may make a graphic image of twins intrauterine growth in the evaluated population. PMID- 8359740 TI - [Doppler flow evaluation of atrio-ventricular valve blood flow in the fetal heart during the second half of normal pregnancy]. AB - 39 normal fetal heart examinations were evaluated since 20 week of gestation to term, and Doppler blood flow was analysed for mitral and tricuspid valves. The measurements were done always in good 4 chamber view and qualitative and quantitative analysis were performed, in terms of describing E and A waves and maximal velocity against gestational age. In all of the cases between 20 and 34 weeks of gestation there were type E < A Doppler waveform, and since 35 week of gestation there was also type E = A. There were only 2 cases with type E > A, both near term. This Doppler waveform may depends on maturity of the fetal myocardium. The maximal velocity for the atrio-ventricular valves did not correlated with gestational age. The average max value for mitral valve was 43 +/ 10 cm/s and for tricuspid valve 50 +/- 11 cm/s (p < 0.01). PMID- 8359741 TI - [Diagnostic and therapeutic procedures in preinvasive disease of the cervix and cervical cancer in pregnancy]. AB - 154 pregnant women with dysplasia and cervical carcinoma of the uterus treated in the Institute in years 1953-1990 underwent investigation. We notice that only 50 pathologies were diagnosed in I trimester of pregnancy and 85% constituted precancerous and early forms of carcinoma of the uterine cervix. Authors presented the model of management and care of pregnancy, labour and puerperium in these patients. Due to this procedure we obtained 90% compatibility of preliminary and final diagnosis. PMID- 8359742 TI - [Micro-glandular hyperplasia of the cervix canal mucosa]. AB - During the period of 1981-1990 2109 diagnostic-therapeutical curettages of the cervical canal and uterus were performed in the Department of Gynecology and Oncology of Medical Academy in Krakow. In histological examinations of scrapings 17 cases (0.8%) of micro-glandular hyperplasia limited to cervical canal have been found. In 14 out of analysed cases curettage have been performed due to metrorrhagia. There were 12 cases of myomatous uterine among them. Two cases were colposcopically suspected of CIN. One woman exhibited a cervical polyps. A connection between micro-glandular hyperplasia and pregnancy and particularly with oral contraception observed in other studies has not been determined. None of the 17 patients were pregnant. They took neither contraceptive pills nor were treated by female hormones. 15 out of examined patients had an estrogenic reaction in cytological evaluation. Decidual transformation of the uterine cervix has not been colposcopically found in any case. Coexistence of micro-glandular hyperplasia and severe dysplasia were revealed in two patients suspected cytologically and colposcopically of CIN. In one case micro-glandular hyperplasia parallel to squamous carcinoma of the cervix has been stated. PMID- 8359743 TI - [Survival, complications and quality of life in patients with breast cancer after ovariectomy and hormonal therapy]. AB - Seventy one women with breast cancer in clinical stage IIIa were treated by chemotherapy and radical operation on the basis five features, namely: survivals, relapses, metastases, quality of life, and post-therapy complications. The two treatment methods were compared. The dependence between survivals and time elapsed between breast surgery and ovariectomy was evaluated. Women treated by ovariectomy suffer from; menopause symptoms, osteoporosis, blood coagulation distortions more after than women treated by hormonotherapy. Tamoxifen therapy increases the rate of breast cancer relapses and probably it is the cause of breast cancer metastases into liver. Women who underwent hormonal castration are professionally active more after them women treated by ovariectomy. Time elapsed between breast surgery and ovariectomy does not affect survivals in stage IIIa. In stage IIIb however, performing later ovariectomy prolongs survivals. PMID- 8359744 TI - [Triploidy as a cause of failure in human reproduction]. AB - Triploidy is a frequent chromosomal abnormality found in 12% of all spontaneous first trimester abortions. Triploidy can result from various mechanisms: failure of segregation during meiosis I or II leads to the formation of gametes with an extra haploid set of chromosomes or abnormally fertilization by two spermatozoa. The authors presents physiological mechanism which prevent polyspermic fertilization, the morphological pictures of triploid early embryos. After implantation of triploid embryos partial embryonal hydatidiform moles develops. Now the possibility of the prevention and treatment of triploid in humans are very limited. PMID- 8359745 TI - [Microstructure of placenta and activity of some respiratory enzymes --in pregnancy with treated and untreated fetal intrauterine hypotrophy syndrome]. AB - The cases of fetal intrauterine hypotrophy syndrome were subjected to rest, dietetic and pharmacological treatment which included intravenous infusions of low molecular Dekstrane, intramuscular injections of Synacthen-Depot, Sadamine and Partusisten. The clear improvement of selected parameters of placenta efficiency during the management was observed. It included: mean increase of blood serum oxytocinase activity about 2.1 U, mean increase of quantity of estrogens excreted in 24-hour urine about 4.1 mg/24 hours, mean decrease of term stabile alkaline phosphatase activity in blood serum about 16 U. The comparison of the state of hypotrophic newborns found in the group with hypotrophy treated during the course of pregnancy with the group of untreated hypotrophy permits to conclude: statistically significant more rarefied occurrence of newborns of low values according to Apgar scale, hypoglycemia, acidosis, anemia as well as respiratory distress syndrome and five-fold diminished perinatal mortality. It was demonstrated a clear correlation between many parameters of structure and activity of oxygenizing enzymes of placentae existed between the group with treated and untreated hypotrophy. PMID- 8359746 TI - [Pregnancy and labor in the patient with arteriovenous congenital fistula]. AB - The paper presents a case of uncomplicated pregnancy in 26-years old primipara suffering from congenital arteriovenous fistula. The clinical picture of disease was manifested by presence of vaso-dilatations in lower and upper limbs and in the vulva, because of which the pregnancy was terminated by cesarean section. Puerperal and postoperative outcome was uncomplicated. In the puerperal period heparin and large-spectrum antibiotic therapy was administered. No cardiovascular or thromboembolic complications were observed. Authors are of opinion, that in face of menace, the pregnancy and labour in the women presenting arterio-vascular fistula have to be considered as situation of high obstetrical risk. PMID- 8359747 TI - The seventh key to facial beauty and TMJ health: proper condylar position. Part 3. AB - This is the eleventh article in a series of articles on orthodontic diagnosis. Only a proper diagnosis can lead to the correct treatment for an individual patient--leading to a balanced profile, a beautiful smile, and a healthy TMJ. This article is to document the first phase of TMJ treatment in patients who are being treated for TMJ Dysfunction related to posterior and/or superior TMJ displacement, and the change in the mandibular position and dental relationships that almost always occurs with proper treatment. The illusion of a posterior openbite "supposedly created" by the splint has led to much misunderstanding and unhappiness with both patients and family dentists. The real "cause" of this posterior openbite and treatment procedures to correct it will be discussed. PMID- 8359748 TI - Achieving excellence in TMJ, functional orthopedics, and case finishing. Part II. Locating position of the mandible. PMID- 8359749 TI - Mandibular whiplash. Part II. An extension flexion injury of the temporomandibular joints. AB - The single most common contributing factor in the onset of TMJ disorders is cranio cervical trauma. This is strongly supported by the referred literature and a wide range of clinical experience. Trauma is also one of the most frequently overlooked factors when developing an occlusion related treatment plan. Failure to take into account a previous injury that has caused permanent damage to the TMJs could prove to be very embarrassing. If the symptoms are in remission at the initiation of occlusal therapy, a tense situation can arise if an old injury becomes acute during treatment and the patient mistakenly assumes that the occlusal therapy was the proximate cause of the flare up in symptoms. Pretreatment screening for TMJ injuries is extremely important and can have substantial impact on the final therapeutic course. PMID- 8359751 TI - [Relevance of psychotherapy methods for gynecology]. PMID- 8359750 TI - The bicuspid buildup ... an alternative in Phase II treatment of craniomandibular dysfunction. Part II. PMID- 8359752 TI - [Female orgasm. Disorders of orgasm and treatment possibilities]. PMID- 8359754 TI - [Erotic aspects of the physician-patient relationship in gynecology]. PMID- 8359753 TI - [Male orgasm. Disorders of orgasm and treatment possibilities]. PMID- 8359755 TI - [The relevance of love in gynecology]. PMID- 8359756 TI - [Woman and death--medicine and modern aspects. A medical historical essay]. PMID- 8359757 TI - [Emotions of the physician in sterility consultation]. PMID- 8359758 TI - [The psychosomatic unit of the gynecology clinic]. PMID- 8359759 TI - [Antepartum CTG: anemia and parvovirus 19 infection]. PMID- 8359761 TI - [Apoptosis: biological and clinical significance. Italian Society of Experimental Hematology, Florence, 18 March 1993. Abstracts]. PMID- 8359760 TI - [Diabetes mellitus and nephrotic syndrome in pregnancy]. PMID- 8359762 TI - [Long-term culture of bone marrow cells: biological aspects and clinical applications. Italian Society of Experimental Hematology. Florence, 18 March 1993. Abstracts]. PMID- 8359763 TI - First metatarsal head-shaft angle: a method of determination. AB - The distal metatarsal angle (DMAA) is a measurement of the relationship between the longitudinal axis of the first metatarsal and the articular surface of the metatarsal head. We measured the DMAA on radiographs with and without markers on the articular edges and compared them with measurements of the anatomic specimens. Based on the studies, the significance of the radiographic measurements to the actual DMAA and the normal distribution of the measurement were determined. PMID- 8359764 TI - Peroneus longus tendon sling in revision surgery for congenital vertical talus: a new surgical technique. AB - When faced with revision surgery for recurrent congenital vertical talus deformity, the tibialis anterior tendon may be deficient or absent as a result of the initial procedure. This tendon cannot then be used as a dynamic sling to dorsiflex the talar neck. We present two cases in which the peroneus longus tendon was transferred dorsally into the talar neck as an alternative to an absent tibialis anterior tendon. Excellent corrections were achieved and maintained. The use of this tendon has not been described previously in surgery for this condition. PMID- 8359765 TI - A treatment algorithm for neuropathic (Charcot) midfoot deformity. AB - Forty-nine feet in 47 patients with midfoot neuropathic foot deformity were referred for care to a comprehensive foot salvage clinic and followed for an average of 3.6 years. Twenty-three initially presented without open ulcers. Two underwent elective Syme's ankle disarticulation amputation, and the others were kept ambulatory with a combination of periods of nonweightbearing cast immobilization, accommodative extra-depth shoes with custom orthotics, and ankle foot orthoses. Twenty-six of the feet initially presented for care with open ulcers and/or chronic osteomyelitis. Twenty-two of these patients underwent 32 surgical procedures. Sixteen underwent debridement of the infected bone and surrounding soft tissues. Excision of large, nonaccommodative boney prominence, termed exostectomy, was performed in eight. Partial excision of the deformed midfoot combined with boney stabilization and attempted arthrodesis, termed partial tarsectomy, were performed in seven. All surgical patients were managed postoperatively with long-term custom accommodative bracing. Follow-up at an average of 3.6 years revealed that all but one of the patients remained ambulatory. Six walk with accommodative shoe gear and persistent stable chronic open ulcers. None required below-knee amputation. Five amputations were performed, three at the Syme's ankle disarticulation level, one at the Chopart's hind-foot level, and one at the mid-foot level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359766 TI - Morphometric analysis of the plantar plate apparatus of the first metatarsophalangeal joint. AB - Reliable and reproducible radiographic assessment of plantar plate integrity of the great toe is possible with standard radiographic techniques. Normal values in 100 pairs of feet (200 feet) are defined for comparison of one foot to the other and absolute values emerge if comparison is not possible. Bipartite sesamoids occurred in 13.5% of 200 feet with a 37% bilaterality. PMID- 8359767 TI - Digital nerves of the foot: anatomic variations and implications regarding the pathogenesis of interdigital neuroma. AB - Seventy-one cadaveric feet were dissected, with attention to communicating branches of the digital nerves, the diameters of the digital nerves, the distance between the metatarsal heads, and the presence or absence of interdigital neuromas. A communicating branch was absent in 52 feet (73.2%) and present in 19 specimens (26.8%). The communication was from the fourth to the third web space common digital nerve (i.e., from the lateral to the medial plantar nerve) in 11 specimens. A reverse communication, from the third to the fourth web space common digital nerve (i.e., from the medial to the lateral plantar nerve), was present in eight specimens. Neuromas were identified in the second web space in 26 specimens and in the third web space in 32 feet. The common digital nerve to the third web space was not thicker in feet with a contribution from the fourth to the third web space nerve. Additionally, the incidence of third web space neuroma in feet with this type of communication was not significantly greater than in those feet without an internervous communication. However, the intermetatarsal head distances and the ratios of the intermetatarsal head distance to the digital nerve diameter in web spaces 2 and 3 were significantly smaller in comparison to spaces 1 and 4 (P < .05). The morphometric data lend support to theories that explain the propensity for neuroma formation in both the second and third web spaces on a mechanical basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359768 TI - Differences in ankle joint complex range of motion as a function of age. AB - The purpose of this study was to determine whether gender- and age-related differences in ankle joint complex (AJC) range of motion (ROM) exist in children (range 9-13 years), adolescents (14-16 years), and young adults (17-20 years), and to compare these data with those published for older subjects (21-79 years) using the same protocol. A total of 120 subjects (58 males and 62 females) ranging in age from 9 to 20 years were tested for AJC ROM using a specifically designed 6 degrees of freedom fixture. All measurements were made with respect to a laboratory coordinate system, and represented assessment of active AJC ROM. Angular displacements for plantarflexion, dorsiflexion, inversion, eversion, abduction, and adduction were digitally recorded and compared. AJC ROMs of females aged 9 to 20 years were generally greater than those for males about all three orthogonal axes. Within each gender, there was a consistent trend for AJC ROM to decrease from a maximum at 14 to 16 or 17 to 20 years to a minimum after age 60 years. The average decrement was greater for females than for males. This study provided evidence to support the contention that age-related and gender differences in AJC ROM do exist. The possibility of minimizing the decline in AJC ROM with age requires further investigation. PMID- 8359769 TI - Ankle arthrodesis placement of cannulated screws. PMID- 8359770 TI - Talar neck fractures. AB - Talar neck fractures represent a serious injury, and a review of the literature reveals the controversies surrounding the treatment options. In spite of the differences, there are many aspects of management where little disagreement exists. Anatomic reduction is the goal in situations where a primary salvage procedure is not performed. If closed treatment is chosen, careful follow-up is necessary to prevent unrecognized displacement as swelling subsides in the cast. Weight-bearing should be delayed until radiographic signs of fracture healing are obvious. There is a growing tendency toward open reduction and internal stabilization of talar neck fractures. Results suggest improved maintenance of reduction, decreased time to union, and a better end result. Prior to attempting any type of salvage procedure, careful assessment of both the tibiotalar and subtalar complex is necessary. The incidence of poor results following a talar neck fracture is disappointingly high. Additional studies of the pathoanatomy and biomechanics may improve our understanding. Controlled prospective clinical series will help clarify the advantages of specific treatment approaches and lead to better clinical results. PMID- 8359771 TI - Defining how the prescription footwear association and the board for certification in pedorthics can help the medical profession. AB - Dorland's Medical Dictionary defines pedorthics as the art concerned with the design, manufacture, fit, and modification of shoes and related foot appliances as prescribed for the amelioration of painful or disabling conditions of the foot and limb. PMID- 8359772 TI - [Worldwide foundation for AIDS research and prevention is organized]. PMID- 8359773 TI - [Variants of chronic polyarthritis with late disease onset. More benign or malignant course in the elderly?]. PMID- 8359774 TI - [Conservative therapy of low back pain. Part 1: Immobilization]. AB - The most common treatment for low back pain is bedrest, the purpose of which is to minimize pain caused by movement. Randomized studies have shown that this form of treatment is of use only over the short term. Whenever possible, the patient should be mobilized again after only 2 days. Long-term immobilization has a number of disadvantages. Lumbar corsets may be considered a form of partial immobilization, and are usually not recommended for unspecific back pain. As initial treatment of acute back pain, short term bedrest with proper positioning of the sufferer, possibly in combination with drug treatment can be employed. PMID- 8359775 TI - [Duplex sonography of dialysis shunts. Noninvasive evaluation of the arteriovenous fistula in dialysis patients]. AB - Duplex sonography permits non-invasive evaluation of both the anatomy and function (flow volume) of the AV-fistula in patients on hemodialysis in a single session. It should be the first imaging procedure to be applied when access to the circulation presents a problem. Comparisons with angiography and surgical reports confirm the adequate sensitivity and specificity of the procedure. Diagnostic problems may occur with ambiguous vascular anatomy, stenoses affecting the anastomosis or central veins. Duplex sonography makes the establishment of the indication for angiography or therapy much more accurate. PMID- 8359776 TI - [Dying in the hospital. Medical and psychological aspects]. AB - For a variety of reasons, the process of dying is taking place ever more frequently in the institution hospital. Apart from the fact that the problem of death continues to be a taboo subject, this is leading to medico-somatic and psychological problems for both the dying person and the so-called "helper". To enable the latter to deal with this existential challenge, he or she must undergo adequate preparation. PMID- 8359777 TI - [Weight reduction with alternative diets. Principles, philosophy, side effects, outcome. Part 2. Alternative diets B]. PMID- 8359778 TI - [Autologous blood and concentrates or donor blood and fresh frozen plasma? On the path of medical decision lurk legal pitfalls (2)]. PMID- 8359779 TI - [Surgical treatment of stroke--the recent trend and problems]. PMID- 8359780 TI - Preparation of three troponin components from puffer skeletal muscle. AB - The Ca(2+)-regulatory proteins, i. e., troponin C, I and T, were prepared from puffer skeletal muscle. The SDS-gel electrophoretic study indicated that the molecular weights of troponin C, I and T were 18, 20 and 30k daltons, respectively. The Ca(2+)-sensitivity of the ATPase activity of the puffer myofibrils was abolished by the removal of troponin C by the CDTA-treatment and then restored by the reconstitution with puffer skeletal troponin C. The treatment with excess troponin T of either puffer or rabbit skeletal muscle at slightly acidic condition resulted in the removal of troponins C and I from the puffer myofibrils. The reconstituted puffer troponin C-I-T gave the Ca(2+) sensitivity to the ATPase activity of puffer desensitized myofibrils in the presence tropomyosin. PMID- 8359781 TI - Effect of substitution of troponin C on the ATPase of bullfrog skeletal myofibrils with troponin C from various muscles. PMID- 8359782 TI - [An autopsy case of severe portal hypertensive gastropathy associated with a large shunt from superior mesenteric to left renal vein in a patient with alcoholic liver cirrhosis]. AB - We report an autopsy case of severe portal hypertensive gastropathy with a large shunt from the superior mesenteric to left renal vein in a patient with alcoholic liver cirrhosis. A 60-year-old man with alcoholic cirrhosis was admitted for tarry stool and ascites. Endoscopic finding revealed multiple red spots and hemorrhagic gastritis at prepylorus of the stomach. Angiography showed a large shunt vessel originating from the superior mesenteric to left renal vein. He died of hepatic failure and DIC following frequent gastrointestinal bleeding. At autopsy, the stomach showed marked congestion of the capillary vessels in the tunica propria mucosa. This finding showed that the gastropathy resulted in the congestion of the gastric veins connecting with the large shunt vessel. PMID- 8359783 TI - Diabetes mellitus-associated glycogen storage hepatomegaly: report of a case and review of the Japanese literature. AB - A huge hepatomegaly was seen in a 30-yr-old female diabetic who was treated with high dose of insulin for her uncontrollable food ingestion. The liver function at the peak of the hepatic enlargement showed a moderate increase of transaminases, alkaline phosphatase, and gamma-glutamyl transpeptidase. The histology of the enlarged liver revealed PAS-positive granules in enlarged hepatocytes, indicating the presence of massive glycogen storage. On admission, she was maintained under a calorie-restricted diet and received approximately 15 to 20 units per day of insulin supplement. At one month after admission, a marked shrinkage of her enlarged liver and restoration of normal liver function were observed concomitantly with the return of fair control of her blood sugar levels. One year later, she had an episode of diabetic ketoacidosis which subsequently was treated with a continuous low-dose infusion of insulin; however, she showed neither hepatomegaly nor liver dysfunction during this episode. There have been 20 cases reported of Japanese diabetics with marked hepatomegaly, in whom the vigorous treatment of diabetic ketoacidosis with insulin seemed to be a trigger of the enlarged liver. This has occurred mostly in patients with insulin-dependent diabetes mellitus. We present a case of non-insulin-dependent diabetes mellitus with glycogen storage hepatomegaly, presumably due to excessive insulin supplements. This suggests that glycogen storage hepatomegaly in diabetics may not be only due to an acute restoration from diabetic ketoacidosis, but may also be due to an overinsulinization in an attempt to maintain a euglycemic condition in spite of excess food intake. PMID- 8359784 TI - Study design for final height determination in Turner syndrome: pros and cons. AB - Early studies on the use of human growth hormone (hGH) for the treatment of Turner syndrome are reviewed and attention is drawn to the higher dose used compared with the doses for growth hormone deficiency (GHD). Patients with Turner syndrome responded less consistently than GHD patients to hGH. The prediction of final height in Turner syndrome from bone age is uncertain - long-term trials are essential to resolve final height questions. The pros and cons of randomized placebo-controlled trials, randomized nontreatment-controlled trials and historical controlled trials are compared, and it is concluded that in the USA, a randomized placebo-controlled trial is the most appropriate study design. The ethical considerations of such a long-term trial, in terms of risk vs. benefit, and the need for a placebo-treated group are also discussed. PMID- 8359785 TI - Dose-dependent effect of growth hormone therapy on glucose metabolism in subjects with Turner syndrome. The German Lilly Ullrich-Turner Syndrome Study Group. AB - Recombinant human growth hormone (GH) is effective in promoting growth velocity in subjects with Turner syndrome. As higher doses are used for this indication than for substitution therapy in GH deficiency, the long-term effects of GH therapy on carbohydrate metabolism represent a safety issue; this is particularly important in Turner syndrome, in which there is an increased prevalence of impaired glucose tolerance. So far, GH therapy has been given to patients with Turner syndrome for up to 7 years without any significant changes having been reported in glycosylated haemoglobin (HbA1c) values, unstimulated and stimulated oral glucose tolerance test (OGTT) blood glucose and serum insulin concentrations. These findings may, however, be influenced by other variables, such as study design, number of subjects or standardization methods applied. Results of an ongoing trial in the FRG, from which 2 years' data on glucose metabolism (as assessed by serial OGTTs) of 72 patients with Turner syndrome are available, indicate that glucose homoeostasis is maintained at the expense of an increase in insulin secretion, which is time- and dose-dependent. Although these changes may be fully reversible on withdrawal of GH. therapy, accurate control of glucose metabolism both during and after GH. treatment is advocated. PMID- 8359786 TI - Results of long-term therapy with growth hormone in two dose regimens in Turner syndrome. Dutch Growth Hormone Working Group. AB - Girls with Turner syndrome were divided according to age (group A 6-12 years, and group B 12-19 years) and human growth hormone (GH) dose regimen (A1 and B1, three injections/week; A2 and B2, six injections/week). All groups responded to GH, 24 IU/m2/week, with an increase in height velocity, though in the older girls, the response was comparatively poor. Therefore, the dose regimens in groups B1 and B2 were increased to 36 IU/m2/week given as six injections in both groups. This change resulted in an increase in height velocity only in group B1. During the first 2 years only, the height velocity was greater in group A2 than group A1. The conclusion is that a regimen of six injections/week is more effective than one of three injections/week in terms of initial height gain and change in predicted adult height. In girls with Turner syndrome aged over 16 years, GH therapy has no significant effect. PMID- 8359787 TI - Growth hormone treatment in Turner syndrome: results of a multicentre study in Japan. The Committee for the Treatment of Turner Syndrome. AB - Patients with Turner syndrome were treated with recombinant human growth hormone (GH) for 3 years. Sixty-eight patients received GH, 0.5 IU/kg/week, while 93 received GH, 1.0 IU/kg/week, by daily subcutaneous injection. Both treatment groups showed a statistically significant increase in growth during treatment. However, the higher dose increased height velocity to a significantly greater extent during the first and second year of treatment. The projected adult height was exceeded by 52 of 71 patients over the age of 14 years. Plasma insulin-like growth factor 1 levels were elevated and no remarkable advances in bone age were observed. There were no other significant changes in physical or laboratory parameters. No glucose intolerance was observed. These results indicate that GH treatment is useful for accelerating growth velocity in patients with Turner syndrome. However, further study will be required to find the most appropriate dose. PMID- 8359788 TI - Safety and efficacy of human growth hormone treatment in girls with Turner syndrome. AB - Six major adverse medical events (AMEs) and 44 minor AMEs were recorded in 6 and 23 patients, respectively, during human growth hormone (GH) treatment of Turner syndrome, equivalent to 118 treatment years. During the first year of GH treatment, there was no change in the SD score (SDS) for systolic or diastolic blood pressure. In a subgroup of 20 patients, there was no change in psychological tests, oral glucose tolerance, glycosylated haemoglobin or serum triglycerides over the first year of GH treatment. The mean total serum cholesterol level fell over this period. The low incidence of adverse medical problems during GH treatment complemented its efficacy. Height velocity in the first year was 7.7 +/- 1.8 cm/year (mean +/- SD) and was correlated with maternal height SDS, though not with paternal height SDS. Some 36% of first-year height velocity SDS could be predicted by the dose of GH and maternal height SDS. PMID- 8359789 TI - Long-term effect of human growth hormone therapy on the prevalence of autoantibodies in Turner syndrome. The Dutch Growth Hormone Working Group. AB - Abnormalities of immune status, particularly a high prevalence (about 50%) of thyroid autoantibodies, have been reported before in Turner syndrome. Results are conflicting as regards other abnormalities of immune function. Growth hormone (GH) has immunomodulatory effects, but results of its effects on GH-deficient children are inconsistent. In this study, 42 girls with Turner syndrome, aged 7.3 19 years, are investigated before, during and after 4 years of human GH therapy. Girls over 12 years old also received ethinyl oestradiol. The prevalence of antithyroid antibodies was 16.7% initially, 35.3% after 24-45 months and 48% after 4 years of therapy though, as there was no control group, it was difficult to conclude that GH was enhancing their appearance. Hypothyroidism was extremely uncommon, and the growth response was no different in those who had the antibodies from those who had not. There were no dramatic increases in prevalence of any of the other antibodies investigated, though the prevalence of parietal cell antibodies was higher than expected. PMID- 8359790 TI - Psychosocial effects of two years of human growth hormone treatment in Turner syndrome. The Dutch Working Group: Psychologists and Growth Hormone. AB - Thirty-eight girls with Turner syndrome were treated for 2 years with human growth hormone. Both parents and patients carried out assessments of the effects of treatment on various aspects of psychosocial functioning. The children used the Piers-Harris Self-Concept Scale and the Social Anxiety Scale for children, while parents were interviewed and filled in the Child Behavior Checklist. Both parents and children used the Therapy Evaluation Scale and the Silhouette Apperception Technique. Teachers completed the Teacher Rating Form. Results showed no significant changes with treatment in self-concept or social anxiety, or in behavioural problems, though immature behaviour was less common after the treatment period. Therapy was evaluated positively, and improvements were apparent in both social and emotional functioning; about a quarter of the patients became more independent, happier and more involved in social interactions. Unrealistic perceptions of present height and expectations of future height were expressed by a large proportion of both children and parents. PMID- 8359791 TI - Psychological aspects of the Canadian randomized controlled trial of human growth hormone and low-dose ethinyl oestradiol in children with Turner syndrome. The Canadian Growth Hormone Advisory Group. AB - Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height, sexual development and psychological status of girls with Turner syndrome. Girls entering the study were randomized either to be treated with recombinant human growth hormone or to act as controls. Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years. However, for the purposes of the psychological study at this time, children receiving oestrogen were excluded from analysis. Girls treated with GH for a period of 2 years showed a significant increase in growth rate, which declined with continued treatment, while the growth rate in the control group remained constant throughout. There was a correlation between the higher growth rate and the girls' perceptions of themselves as more intelligent, more attractive, having more friends, greater popularity and experiencing less teasing than the untreated group. Growth rate was not correlated with family or school functioning. PMID- 8359792 TI - Neurocognitive function and brain imaging in Turner syndrome--preliminary results. AB - Girls with Turner syndrome were investigated in order to determine the anatomical differences in their brains compared with those of normal age-matched female controls, and to relate these differences to deficits in neurocognitive function with a view to understanding the abnormal brain development in Turner syndrome. During the 2-year study period, it is planned to evaluate 50 girls with Turner syndrome and 50 age-matched controls. A wide range of authentic neurocognitive tests will be applied to establish the neurocognitive profile, and brain anatomy will be studied by magnetic resonance imaging (MRI). Ten patients with Turner syndrome have been evaluated by neurocognitive testing to date, and 8 girls with Turner syndrome and 13 controls have had MRI scans performed. There is preliminary evidence of both specific and generalized processes affecting brain development and cognitive function in Turner syndrome. The evidence of a role for sex hormones in socio-behavioural and cognitive abilities in Turner syndrome is discussed. PMID- 8359795 TI - Development of human peribiliary capillary plexus: a lectin-histochemical and immunohistochemical study. AB - We investigated the development of human intrahepatic peribiliary capillary plexus by lectin-histochemistry and immunohistochemistry, using 40 fetal livers of various gestational ages, 52 postnatal livers of various ages, and 10 adult livers. In the earliest developmental stage of intrahepatic bile ducts ("the stage of ductal plate"), no vasculatures were found around the ductal plate, but progenitor vascular cells positive for von Willebrand factor, Ulex europaeus agglutinin I and succinylated wheat germ agglutinin appeared in the mesenchyme of the portal tracts. In "the stage of biliary cell migration into the mesenchyme," the progenitor vascular cells transformed into capillaries positive for von Willebrand factor, Ulex europaeus agglutinin I, and succinylated wheat germ agglutinin. In "the stage of bile duct formation," capillaries began to surround the bile ducts (immature peribiliary capillary plexus). The capillaries of the immature peribiliary capillary plexus proliferated and formed premature peribiliary capillary plexus around 40 wk of gestation in large bile ducts and around 6 wk after birth in small bile ducts. The former was composed of inner and outer layers, whereas the latter consisted of scattered capillaries without layer formation. The premature peribiliary capillary plexus continued to proliferate in the postnatal life and reached an adult and mature state around 15 yr. These data suggest that endothelial cells of capillaries of peribiliary capillary plexus derive from mesenchyme at the earliest stage of bile duct development and that the development and maturation of peribiliary capillary plexus progress parallel to those of the intrahepatic bile ducts. PMID- 8359793 TI - Propranolol compared with propranolol plus isosorbide dinitrate in portal hypertensive patients: long-term hemodynamic and renal effects. AB - The long-term hemodynamic and renal effects of propranolol were compared with those of propranolol plus isosorbide dinitrate in 44 portal-hypertensive alcoholic cirrhotic patients. Eight control patients, 8 patients receiving propranolol and 14 patients receiving propranolol plus isosorbide dinitrate were hemodynamically evaluated. Renal function was studied in a fourth group of 14 patients receiving propranolol plus isosorbide dinitrate. Portal pressure decreased more (p < 0.05) with combined therapy (-21.6%, from 19.5 +/- 4.8 to 15.4 +/- 4.3 mm Hg) than with propranolol alone (-12.5%, from 19.9 +/- 1.2 to 17.4 +/- 1.8 mm Hg). Serum urea and creatinine levels, plasma sodium concentration, urine volume and urinary sodium excretion showed nonsignificant changes in all groups studied. Combined therapy induced a significant (p < 0.05) decrease in plasma renin activity (from 4.42 +/- 4.7 to 1.59 +/- 1.9 ng/ml/hr) and nonsignificant reductions in plasma aldosterone concentration and creatinine clearance. None of the eight patients with ascites or history of ascites not receiving isosorbide dinitrate showed evidence of impairment in renal sodium metabolism during the study period. In contrast, 8 of the 14 patients (57%) with ascites or history of ascites receiving isosorbide dinitrate showed impairment in renal sodium metabolism (p < 0.01), as reflected by the development or worsening of ascites and the need of higher diuretic requirements. Long-term combined administration of propranolol plus isosorbide dinitrate is superior to propranolol alone in the pharmacological treatment of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359796 TI - Visualization of the uptake and processing of oxidized low-density lipoproteins in human and rat liver. AB - The interaction of oxidized human low-density lipoproteins with human and rat liver was analyzed by light and electron microscopy. At the light microscopic level oxidized low-density lipoprotein was visualized by the fluorescent dye 1,1' dioctadecyl 3,3,3',3' tetramethyl indocarbocyanine perchlorate, whereas at the electron microscopic level, an indirect immunolabeling procedure was used that detected the apoprotein B of the oxidized low-density lipoprotein. In rats, oxidized low-density lipoprotein was administered intravenously, and uptake by human liver was studied by perfusion of tissue blocks. Both in human and in rat liver, fluorescently labeled oxidized low-density lipoprotein was mainly found to become concentrated in Kupffer cells and, to a lesser extent, in endothelial cells. In both species the cell association of fluorescently labeled oxidized low density lipoprotein could be inhibited by preadministration of polyinosinic acid, indicating a scavenger receptor-mediated process. At the electron microscopic level, oxidized low-density lipoprotein was found to bind mainly to areas of the plasma membrane of the Kupffer cells without clathrin coating, although binding to coated regions was also noticed. Internalization of the ligand occurred through coated vesicle formation and through membrane folding of interacting lamellipodia and wormlike structures. No indication for phagocytosis of aggregated oxidized low-density lipoprotein particles was noticed. After internalization, the immunoreactive oxidized low-density lipoprotein was detected in relatively electron-lucent endosomes and, subsequently, in lysosomes. Endothelial cells internalized oxidized low-density lipoprotein solely through coated pits, after which the particles were transferred through endosomes into lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359794 TI - Secretion of soluble chemotactic factors, including interleukin-6: a mechanism for the recruitment of CD8-positive T lymphocytes to human liver allografts during rejection. AB - In 35 patients receiving first liver transplants we assessed the chemotactic responsiveness of peripheral blood lymphocytes to bile, the subset composition of the responding population and the ability of peripheral blood lymphocytes to produce chemotactic factors. In 13 patients in whom acute rejection developed, lymphocyte chemotaxis in vitro was significantly greater in bile sampled 1 or 2 days after transplantation and before episodes of acute rejection than in bile sampled when rejection was clinically apparent or after steroid therapy during stable graft function. The chemotactic factors present showed preferential activity for CD8-positive T cells. Bile sampled during the same posttransplant periods from 11 patients who did not exhibit rejection showed significantly less chemotactic activity. In vitro cultured peripheral blood lymphocytes from patients in whom rejection developed produced lymphocyte chemotactic factors that induced a similar pattern of chemotactic responsiveness with preferential activity for CD8-positive T cells. Separate culture of purified CD4-positive and CD8-positive T cells obtained from patients in whom rejection developed showed that CD4-positive cells produced the factor(s). Analysis of the subset responses of normal peripheral blood lymphocytes to a variety of chemotactic cytokines showed interleukin-6 to have specificity similar to that observed with chemotactic bile, mixed peripheral blood lymphocyte culture supernatants and supernatants of CD4-positive T cells. Chemotactic activity was reduced by 45% to 90% in five chemotactic bile samples and three peripheral blood lymphocyte culture supernatants by treatment with affinity purified interleukin-6 monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359797 TI - Distribution of B lymphocytes in nonsuppurative cholangitis in primary biliary cirrhosis. AB - Primary biliary cirrhosis is characterized by the immune-mediated, nonsuppurative destruction of intrahepatic small bile ducts, with significant T-cell involvement. To date, B cells in livers of primary biliary cirrhosis patients have been ignored in immunopathological evaluations of nonsuppurative cholangitis. This study aimed to correlate the distribution of activated T and B cells with the histopathology of nonsuppurative cholangitis in primary biliary cirrhosis, with emphasis on B cell infiltration. The distribution of activated T and B cells and the histopathology in primary biliary cirrhosis were heterogeneous in bile ducts showing nonsuppurative cholangitis; they were also heterogeneous in various parts of a given bile duct. Although activated T cells were significantly involved in the occurrence of nonsuppurative cholangitis, B cell-predominant reaction or cholangitis and B-cell infiltration into the biliary epithelial layer were also prominent in some nonsuppurative cholangitis. Many bile ducts with nonsuppurative cholangitis of various histological types showed intermixed activated T- and B-cell infiltration. These findings indicate that immune mechanism(s) involving B cells and, probably, humoral immunity are at work in the occurrence of nonsuppurative cholangitis and the destruction of bile ducts in primary biliary cirrhosis. Cell-to-cell interactions of activated T and B cells should therefore be evaluated in livers of patients with primary biliary cirrhosis. PMID- 8359798 TI - Increased plasma interleukin-8 concentrations in alcoholic hepatitis. AB - Patients with alcoholic hepatitis often have hepatic polymorphonuclear leukocyte infiltration and neutrophilia. Interleukin-8 is a cytokine that stimulates neutrophil chemotaxis and release of lysosomal enzymes. It is made by several types of cells, including fibroblasts, Kupffer cells and hepatocytes. In this study, serial plasma interleukin-8 concentrations were measured with enzyme linked immunosorbent assay in 40 consecutive patients with moderate-to-severe alcoholic hepatitis over a 6-mo period. Two control groups included 10 patients without clinically important liver disease admitted for treatment of alcohol dependence and 12 healthy male volunteers. The mean plasma interleukin-8 level on admission was markedly increased: 695 +/- 146 pg/ml in the alcoholic hepatitis patients. The alcohol-dependent control group and the normal volunteer controls had mean interleukin-8 concentrations of 106 +/- 28 pg/ml and 10 +/- 5 pg/ml, respectively. Initially increased interleukin-8 levels in alcoholic hepatitis patients decreased to a mean of 182 +/- 42 pg/ml over the first month; levels had decreased further to 124 +/- 79 pg/ml after 6 mo. Increased interleukin-8 concentrations in patients with alcoholic hepatitis suggest a role for interleukin-8 in the neutrophilia and hepatic polymorphonuclear leukocyte infiltration of alcoholic hepatitis. PMID- 8359799 TI - Spatial and temporal patterns of gene expression for the proteoglycans biglycan and decorin and for transforming growth factor-beta 1 revealed by in situ hybridization during experimentally induced liver fibrosis in the rat. AB - Expression of the proteoglycans biglycan and decorin and of transforming growth factor-beta 1 at various stages of liver fibrosis induced experimentally in rats by oral administration of thioacetamide was examined. Using in situ hybridization combined with immunocytochemical staining for cell-type characteristic markers, we demonstrate spatial and temporal expression patterns specific for each of the genes. Biglycan gene expression levels coincided tightly with the activity and extent of fibrosis, fat-storing cells and their transformed form, the myofibroblast-like cells, being the major contributors. Decorin messenger RNA was detectable only after the transition to the chronic inflammatory stage in nonparenchymal cells of periportal fields and, transiently, in the forming septa. In the cirrhotic stage, expression was detected solely in periportal fields with enhanced bile duct proliferation. Transforming growth factor-beta 1 expression was undetectable in normal liver. During the subacute inflammatory stage, a hepatocyte subpopulation expressing low levels of transforming growth factor-beta 1 occurred at the limiting plate. With the progression of fibrosis, transforming growth factor-beta 1 expression levels increased considerably but remained restricted to the mesenchymal cells of the fibrotic septa. PMID- 8359800 TI - Effect of chronic iron overload on procollagen gene expression. AB - The pathogenesis of hepatic fibrosis and cirrhosis in genetic hemochromatosis may involve a direct effect of excess iron on collagen synthesis in the liver. To investigate this theory, we measured procollagen messenger RNA levels (types I, III and IV) in the livers of rats in which we produced chronic parenchymal iron overload by feeding them dietary carbonyl iron (2.5%, wt/wt) for up to 18 mo. This feeding resulted in predominantly parenchymal iron deposition in a periportal distribution similar to that seen in genetic hemochromatosis. Increased amounts of collagen fibrils were observed in iron-loaded livers on electron microscopy; all iron-loaded livers showed some periportal fibrosis. Although very high hepatic iron concentrations (range = 340 to 1,100 mumol/gm dry wt) were achieved in the carbonyl iron-loaded rats, we saw no consistent difference between steady-state messenger RNA levels for procollagens types I, III and IV in control and iron-loaded livers examined at five different time points up to 18 mo. Messenger RNA levels of the cytokine transforming growth factor-beta 1, which has been implicated as having a role in the production of extracellular matrix proteins, were also measured. No significant differences were observed between iron-loaded and control livers. These results suggest that excess parenchymal iron does not have a direct effect on the expression of the procollagens or transforming growth factor-beta 1 genes in iron-loaded livers and that factors other than, or in addition to, iron are necessary for fibrosis to occur. PMID- 8359801 TI - Liver carcinogenesis associated with feeding of ethionine in a choline-free diet: evidence against a role of oval cells in the emergence of hepatocellular carcinoma. AB - In an attempt to clarify the role of oval cells in the emergence of hepatocellular carcinoma, we fed rats a choline-free diet containing 0%, 0.05% or 0.1% ethionine. The incidence and nature of premalignant and malignant hepatic lesions were then related to the degree of oval cell proliferation. Intake of choline-free diet alone for up to 12 mo was associated with minimal oval cell proliferation; cholangiofibrosis, hepatocellular nodules and hepatocellular carcinoma were observed in 55%, 23% and 14% of the animals, respectively. When rats were given the choline-free diet with 0.05% ethionine, proliferation of oval cells was more pronounced; after a 6- to 12 mo feeding period, cholangiofibrosis (57%) was again observed. However, hepatocellular nodules (91%) and hepatocellular carcinoma (74%) were the most common lesions seen with this feeding regimen. Finally, rats fed the choline-free diet with 0.1% ethionine had massive oval cell proliferation and progressive loss of parenchymal liver tissue. Most of these animals died before they had consumed the choline-free diet with 0.1% ethionine for 12 mo. Rats in this group (96%) exhibited large and numerous cholangiofibrotic lesions, but hepatocellular nodules and carcinoma were not detected. In all animals of each experimental group, hyperplastic bile duct cells in areas of cholangiofibrosis and oval cells were positive for cytokeratin 19, an intermediate filament protein present only in bile duct cells in normal liver. Hepatocellular nodules and hepatocellular carcinoma were invariably negative for cytokeratin 19. We interpret these findings to suggest that oval cells are not involved in the histogenesis of hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359802 TI - Ethinyl estradiol decreases acidification of rat liver endocytic vesicles. AB - Treatment with ethinyl estradiol is known to impair bile formation, bile acid transport and Na,K-ATPase activity, to alter receptor-mediated endocytosis and transcytosis of IgA and asialoorosomucoid and to affect membrane lipid composition and fluidity. Because appropriate sorting and trafficking of asialoorosomucoid requires adequate acidification of endocytic vesicles by a lipid-sensitive electrogenic proton pump, we examined the effects of 5 days of treatment with ethinyl estradiol (5 mg/kg body wt, subcutaneously) on acidification of early endosomes prepared from male rat livers. Littermate control animals received equal volumes of the solvent propylene glycol. Pretreatment with ethinyl estradiol reduced ATP-dependent initial rates of endosome acidification by 11% to 25% when measured in potassium medium containing 0 to 140 mmol/L chloride; these differences were significant at four of six chloride concentrations tested. The proton pumps of ethinyl estradiol and propylene glycol endosomes exhibited similar Michaelis-Menten constants for MgATP (Michaelis-Menten constant of 63 and 66 mumol/L in the absence of chloride and 101 and 126 mumol/L in the presence of chloride, respectively). Acidification of ethinyl estradiol and propylene glycol endosomes changed in the same manner when various cations or anions were substituted for potassium gluconate, although the effects of ethinyl estradiol were less marked in the absence of K+. Kinetics of inhibition for ethinyl estradiol and propylene glycol endosomes were similar for the proton pump inhibitors N-ethylmaleimide (50% inhibitory concentrations of 13.5 and 18.1 mumol/L), dicyclohexylcarbodiimide (50% inhibitory concentrations of 206 and 216 mumol/L) and bafilomycin A (50% inhibitory concentrations of 11 and 6 nmol/L). Although initial rates of acidification were slower in ethinyl estradiol endosomes, ATP-dependent steady-state vesicle interior pH was the same as that of propylene glycol endosomes over a range of chloride concentrations; this appeared to be due mainly to a trend toward decreased proton leak rates in ethinyl estradiol endosomes. Overall, ethinyl estradiol treatment modestly decreased initial rates of acidification and vesicle proton leakage, perhaps because of changes in endosome lipid composition; differences in the number, density or activation state of proton pumps; or differences in endosome geometry. Because the decrease in acidification rates was small, the effects of estrogen on the efficiency of uncoupling of endocytosed ligands such as asialoorosomucoid from their receptors in early endosomes; thus the rates of sorting and distribution of ligands remain unclear. PMID- 8359803 TI - Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension. AB - Although prostaglandins are thought to be involved in the hyperdynamic circulation of portal hypertension, the role of this substance has not been elucidated. Dose-response curves, the hemodynamic effects of prostacyclin (20 micrograms/kg) and its inhibitor indomethacin and measurements of plasma and urinary levels of 6-keto-prostaglandin F1 alpha were compared in three groups of six rats each: normal, with portal vein stenosis and with secondary biliary cirrhosis. Plasma and urinary levels of 6-keto-prostaglandin F1 alpha were higher in rats with portal vein stenosis and cirrhotic rats than in normal rats. Dose response curves showed similar maximal decreases in arterial pressure in the three groups, whereas the maximal increase in portal pressure was less marked in cirrhotic rats than in normal rats and rats with portal vein stenosis. In normal rats, prostacyclin increased cardiac output by 21% and portal pressure by 41%. Similar increases were observed in rats with portal vein stenosis. In contrast, prostacyclin did not affect cardiac output and portal pressure in cirrhotic rats. Indomethacin induced a more marked vasoconstrictive effect in normal rats than in cirrhotic rats. This study shows that prostacyclin plays a role in the hemodynamic alterations in portal hypertension. Moreover, the hyporeactivity observed in cirrhotic rats suggests that prostacyclin plays a major role in the circulatory changes of portal hypertension due to chronic liver disease. PMID- 8359804 TI - Involvement of nitric oxide and prostaglandins in gastric mucosal hyperemia of portal-hypertensive anesthetized rats. AB - This study investigates the effects of inhibition of nitric oxide synthesis by NG nitro-L-arginine methyl ester (L-NAME), the inhibition of prostaglandin synthesis with indomethacin and the combined effects on gastric mucosal hyperemia of ketamine-anesthetized rats with portal hypertension induced by partial portal vein ligation. The hydrogen gas-clearance technique was used for measurement of gastric mucosal blood flow. Blood pressure increased with L-NAME administration in a similar manner in portal-hypertensive and sham-operated rats. Low doses of L NAME (1 and 3 mg/kg, intravenously) caused a significant and dose-dependent reduction in gastric mucosal blood flow in portal-hypertensive rats but had no effect on sham-operated animals. With a higher dose of L-NAME (13 mg/kg, intravenously), a significant decrease in gastric mucosal blood flow was observed in both portal-hypertensive and sham-operated rats. Indomethacin pretreatment (5 mg/kg, subcutaneously) caused a significant decrease in basal gastric mucosal blood flow of portal-hypertensive rats but did not modify this parameter in sham operated animals. In sham-operated rats pretreated with indomethacin, the lower dose of L-NAME (3 mg/kg) did not significantly modify basal gastric mucosal blood flow. Likewise, pretreatment with indomethacin in sham-operated rats did not augment the significant reduction in gastric mucosal blood flow produced by the higher dose of L-NAME. In portal-hypertensive rats the significant dose-dependent reduction in gastric mucosal blood flow induced by L-NAME (3 and 13 mg/kg) was not significantly altered by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359805 TI - Role of platelets in hepatic allograft preservation injury in the rat. AB - Cold preservation of liver allografts injuries hepatic sinusoidal lining cells. This injury is exacerbated on reperfusion, in part because of adhesion of leukocytes. Platelets also adhere to activated endothelial surfaces. In this study we examined the role of platelets in preservation injury. Our specific aim was to determine whether the degree of platelet adhesion on reperfusion of preserved rat livers was related to duration of cold or warm ischemia and whether platelet adhesion resulted in injury to allografts. We also examined the effect of prior activation of platelets on adhesion and injury. Rat livers were preserved at 1 degree C for different time periods in University of Wisconsin solution and then reperfused for 3 hr on the isolated perfused rat liver system with Krebs-Henseleit solution to which unactivated isolated rat platelets were added. Other livers were rewarmed before reperfusion or reperfused with activated platelets. Platelets were lost from the circulation in all studies; the percentage reduction of circulating platelets was dependent on the length of preservation. The initial platelet concentration did not affect the rate of reduction of platelets in the circuit. Rewarming before reperfusion increased platelet adherence, and prior activation also increased adherence. With electron microscopy we determined that platelets adhered in small aggregates to endothelial cells or endothelial cell remnants. Adherent platelets appeared more activated and contained fewer granules than did unperfused platelets. Liver injury as measured by release of transaminases into perfusate was worsened by longer periods of cold preservation and by addition of rewarming to the protocol. The presence of platelets under these circumstances aggravated injury. Prior activation of platelets also increased the extent of injury. These studies show that platelets have an important role in cold preservation-reperfusion injury. PMID- 8359806 TI - Effect of ethanol on rat fetal hepatocytes: studies on cell replication, lipid peroxidation and glutathione. AB - Studies have shown that ethanol at moderate concentrations inhibits epidermal growth factor-dependent replication of fetal rat hepatocytes in culture. This may account for the growth/development impairment associated with fetal alcohol syndrome and decreased liver regeneration in alcoholic liver disease. In this study, we further define the mechanism(s) of the negative impact of ethanol on fetal rat hepatocytes and provide evidence that ethanol-induced injury to these cells is associated with membrane damage caused by lipid peroxidation, altered cell glutathione homeostasis and deranged mitochondrial structure and function. Exposure of fetal rat hepatocyte replication to ethanol (2 mg/ml) promptly resulted in blockade of replication, as indicated by a 40% reduction in DNA synthesis (p < 0.05). Assessment of cell injury on the basis of lactate dehydrogenase and ALT leakage indicated a statistically significant but not appreciable effect, whereas 51Cr leakage was more substantially increased (p < 0.05). Within 6 hr of ethanol exposure, superoxide radical levels increased more than twofold (p < 0.05). We noted a 56% increase in levels of diene conjugates, a 131% increase in malonaldehyde concentration and a 66% increase in fluorescent products of lipid peroxidation (all p < 0.05). Glutathione levels were decreased to 47% below control values (p < 0.05). Electron microscopic studies illustrated a slight disruption of mitochondrial structure (enlargement of mitochondria and dilation of cristae). This disruption was accompanied by mitochondrial swelling (increased permeability), altered mitochondrial membrane potential (a 16% decrease in rhodamine uptake), a 28% decrease in succinate dehydrogenase activity and a 30% decrease in cellular ATP level (p < 0.05). Pretreatment of fetal rat hepatocytes with 0.1 mmol/L N-acetylcysteine or S-adenosylmethionine for 24 hr prevented the ethanol-induced reduction of ATP and glutathione levels, essentially restored cell replication, ameliorated 51Cr leakage and decreased malonaldehyde and diene conjugate levels to 41% to 65% and 25% above control values, respectively. Pretreatment with 0.1 mmol/L vitamin E fully normalized malonaldehyde and diene conjugate levels and 51Cr leakage but failed to improve ATP levels or to increase significantly cell replication and glutathione levels. Concomitant administration of glutathione precursors with ethanol, rather than pretreatment, did not alter the impaired cell replication. Thus our data underscore the importance of cellular glutathione and ATP in preventing ethanol induced decreases in fetal cell replication and suggest that alleviation of cellular lipid peroxidation alone is not sufficient to prevent this abnormality in fetal rat hepatocyte function. PMID- 8359808 TI - Budget trends and issues affecting biomedical research: a perspective from the National Institute of Diabetes and Digestive and Kidney Diseases. PMID- 8359807 TI - Role of newly synthesized cholesterol or its metabolites on the regulation of bile acid biosynthesis after short-term biliary diversion in the rat. AB - Cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the bile acid biosynthetic pathway, is thought to be regulated by hydrophobic bile acids through negative feedback control. The role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase is more controversial, in part because of incomplete understanding of the relationship between the pathways of cholesterol synthesis and degradation. The main objective of this study was to define the interaction between these two pathways in an experimental model in which the supply of newly synthesized cholesterol was interrupted by sustained infusion of mevinolin (lovastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) or accelerated by a continuous infusion of mevalonate, a cholesterol precursor. The study was carried out in rats subjected to short-term bile fistula. In one set of experiments, rats were treated postoperatively with mevinolin (5 mg/kg loading dose followed by 2 mg/kg/hr infusion), mevalonate (180 mumol/hr infusion) or both for up to 96 hr. In a separate set of experiments, rats were infused intraduodenally with taurocholate (36 mumol/100 gm/hr for up to 96 hr). We determined cholesterol 7 alpha hydroxylase- and HMG-CoA reductase specific activities at those time intervals, whereas bile acid synthesis rates were determined throughout the study. Compared with rats not subjected to surgery, rats with short-term biliary diversion had increases in cholesterol 7 alpha-hydroxylase activity of 259% and 827% at 48 and 96 hr, respectively. The increase in bile acid biosynthesis was less pronounced. Continuous infusion of mevinolin completely prevented increases in cholesterol 7 alpha-hydroxylase specific activity and bile acid biosynthesis at both time intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359809 TI - Amino acid transport and glutathione homeostasis: what is the mechanism for cysteine uptake from bile? PMID- 8359810 TI - Urinary copper excretion after penicillamine challenge in children with prolonged hepatitis A infection. PMID- 8359811 TI - Association between heterozygous alpha 1-antitrypsin deficiency and genetic hemochromatosis. PMID- 8359812 TI - Risk of ovarian cancer and genetic relationship to other cancers in families. AB - The risk of ovarian and other cancers was assessed in first-degree relatives of patients with ovarian cancer from an analysis of 391 pedigrees. Overall there was a significant increase in the risk of ovarian cancer (4.5-fold; p < 0.001). The risks were 14.2- (p < 0.001), 5.2- (p < 0.001) and 3.7-fold (p < 0.001) for relatives of patients diagnosed before 45, between 45 and 54 and after the age of 55, respectively. There was no significant increase in the risk of cancers of the uterus, stomach, lung, colorectum or prostate. There was, however, an overall increase in the risk of breast cancer (1.3-fold; p < 0.05). The risk was highest for those relatives of patients diagnosed with ovarian cancer before the age of 55 (2.2-fold; p < 0.01). These results support the role of genetic factors in the aetiology of ovarian cancer and provide further evidence for the existence of a breast-ovarian family cancer syndrome, which may result from the pleiotropic effects of the same gene in some families. PMID- 8359813 TI - Absence of the atypical mitochondrial aldehyde dehydrogenase (ALDH2) isozyme in Saskatchewan Cree Indians. AB - Three methods were employed to assess whether human volunteers (Caucasian, Asian or Cree Indian) possessed the typical or atypical mitochondrial aldehyde dehydrogenase (ALDH2) isozyme. These methods were: (1) questioning individuals about facial flushing responses following alcohol consumption; (2) application of the ethanol skin patch test, and (3) direct analysis using isoelectric focusing and activity staining of ALDH activity in hair root samples. The results from the three methods were in good agreement and revealed that only the typical ALDH2 isozyme was expressed in Saskatchewan Cree Indians. In agreement with previous reports, the typical ALDH2 was expressed in the Caucasian group of subjects, while both the typical and atypical forms were expressed in the Asian subjects. PMID- 8359814 TI - Serum protein polymorphisms (GC, TF, and PI subtypes) in the Basque population of Alava. AB - Group-specific component (GC), transferrin (TF) and alpha-1-antitrypsin (PI) polymorphisms have been studied in the Basque population of Alava. The following gene frequencies were found: GC*1S = 0.525, GC*1F = 0.109, GC*2 = 0.366; TF*C1 = 0.793, TFC*2 = 0.171, TF*C3 = 0.032, TF*B = 0.003; PI*M1 = 0.611, PI*M2 = 0.164, PI*M3 = 0.101, PI*M4 = 0.019, PI*S = 0.101, PI*T = 0.003, PI*Z = 0.002. These results show that there is heterogeneity within the Basque population. In comparison with other populations from the Iberian Peninsula, the Basques from Alava show significant differences only for the PI system. PMID- 8359816 TI - Haptoglobin types in Chinese ethnic groups. AB - The distribution of haptoglobin (HP) types was examined in six different Chinese ethnic groups. The gene frequencies were compared among these groups and to those reported in other Chinese Han populations. The effects of sex and age on the distribution of HP types are also discussed. PMID- 8359815 TI - Genetic variation around the collagen IV 1a gene locus and proliferative retinopathy in type 2 diabetes mellitus. AB - The development of proliferative retinopathy in type 2 diabetes mellitus may be under genetic control. A well-documented pathological change in the fundal capillaries of patients with diabetic retinopathy is basement membrane thickening, with an increased amount of collagen IV protein. Variation at the collagen 1a IV gene therefore may explain familial susceptibility to this complication. It has been previously reported that genetic variation at the collagen 1a locus, as shown by allelic association with a HindIII restriction site, predisposes to diabetic nephropathy where basement membrane thickening is also prevalent. In order to test the hypothesis that the collagen 1a IV gene locus is important in the development of diabetic retinopathy, a population association study was performed comparing allele frequencies of the HindIII RFLP in diabetic patients with retinopathy and controls. No statistically significant differences were found between allele frequencies or genotypes in the two groups. The future use of similar studies in diabetic retinopathy is discussed. PMID- 8359817 TI - SHIN, a low frequency red cell antigen, found in two Japanese blood donors. AB - A low frequency red cell antigen, SHIN, was detected in two Japanese blood donors. Red cells of the first propositus reacted, in pretransfusion tests, with the serum of a previously untransfused male patient. The second propositus was disclosed when anti-SHIN was used to screen red cells from 3,000 random blood donors in Tokyo: a frequency of 0.03% in this population. Family studies showed SHIN to be inherited as an autosomal dominant character and not to be part of the MNS, FY, JK or P1 blood group systems. Anti-SHIN is not a common antibody in normal sera but was found in about 10% of multispecific sera used in investigation of low frequency antigens. PMID- 8359818 TI - Haptoglobin subtypes in two Spanish Pyrenean populations. AB - Haptoglobin subtypes have been determined in two population samples, one of them from the Pyrenean Valley of Pallars Sobira in the province of Lerida and other from the Garrotxa region, province of Gerona. The obtained frequencies have been compared with other Pyrenean and European populations. Our results contrast with the absence of HP*2FF in the north-eastern district of the Pyrenees and suggest a more extensive distribution of this allele in European populations. PMID- 8359819 TI - Genetic affinities of Buryat populations and other Mongoloids of Siberia. AB - Variation at ten polymorphic loci (ABO, RH, PGD, ACP, PGM1, GLO1, ESD, ADA, GC, TF) was studied in a sample of 326 Buryat newborns from Ulan-Ude. The genetic relationships between Buryat and other Mongoloids from Central and Northern Asia were assessed; close similarity was found between the Buryat, Mongol, Yakut, Chulym and Kyzyl populations. PMID- 8359820 TI - Multipoint mapping under genetic interference. AB - Genetic chiasma interference occurs when one crossover influences the probability of another crossover occurring nearby. While interference is known to occur in humans, it is typically ignored when computing multipoint likelihoods for genetic mapping. This biologically unsound assumption of no interference facilitates the calculation of the likelihoods at the expense of reduced power to accurately construct a genetic map. We have developed a computer program that calculates multipoint likelihoods of three-generation nuclear families while taking interference into account. In our program, interference is modelled by using a map function to convert genetic distances into recombination fractions. We can determine which of several map functions best fits the data by comparing the multipoint likelihoods of the data under each map function. Since the distribution of the difference between likelihoods is unknown, we use a simulation approach to determine the statistical significance of our results. When our program is applied to six loci, D10S34, D10S19, D10S16, D10S14, D10S4, and D10S20, from the CEPH consortium map of chromosome 10, we find significant evidence in favor of positive interference as modelled by the Sturt map function. PMID- 8359821 TI - Successful technique for the selective production of monoclonal antibodies against a major allergenic component in timothy pollen extract. AB - Monoclonal antibodies (MAbs) were selectively raised against a major allergenic component of 38 kD in timothy grass pollen (Phleum pratense). We used a special prefractionating technique to isolate the 38 kD allergen, because immunizations with crude pollen extract had resulted in a wide variety of antibodies against other determinants, and cross-reactions between different-sized proteins occurred. Pollen extract was separated by Western blotting. Strips of the nitrocellulose membrane containing the allergen were excised, dispersed into allergen bearing particles, and used for immunization of BALB/c mice. Five MAbs were obtained that reacted with the 38 kD allergen. Four of these antibodies (BF 1, DC 9, EB 4, GE 2) exclusively detected the 38 kD protein, while one MAb (EB 6) additionally bound to a 32 kD allergen. Epitope mapping with the 3 IgG 1 antibodies (BF 1, EB 6, DC 9) was performed by ELISA inhibition tests using the purified 38 kD component. The antibodies did not interfere with each other. This confirms that they bind to different sites of the 38 kD molecule. Only a weak inhibitory effect of the MAbs on the binding of patient's IgE was determined, we suppose that the MAbs do not bind to IgE reactive epitopes. For standardization and further characterization of the 38 kD protein by peptide mapping the MAbs will be useful tools. PMID- 8359822 TI - Bispecific monoclonal antibodies to human interleukin 2 and horseradish peroxidase. AB - Hybrid hybridomas (tetradomas), producing bispecific monoclonal antibodies (bmabs) binding to both interleukin 2 and horseradish peroxidase were obtained by fusing IL 2-specific and HRP-specific hybridomas. Parental hybridomas were labelled prior to the fusion with fluorescein isothiocyanate and tetramethylrhodamine isothiocyanate. Bifluorescent (tetradoma) cells were sorted out using fluorescence activated cell sorter. Two clones, designated D8C1/G and H7C11/H were shown to secrete bmabs over at least 6 months growth in culture. Bmabs have been purified from mouse ascites by ammonium sulfate precipitation and affinity chromatography on immobilized peptide, modelling corresponding IL 2 epitope. The purity of antibodies obtained was characterized by capillary electrophoresis. The possibility of using these antibody preparations in rIL 2 analysis was evaluated in two types of EIA: direct and competitive solid-phase EIA. Both assays had similar sensitivity of about 1.5-4 ng IL 2 per ml. PMID- 8359823 TI - Production of stable rabbit-mouse heterohybridomas: characterization of a rabbit monoclonal antibody recognizing a 180 kDa human lymphocyte membrane antigen. AB - Polyclonal rabbit antihuman thymocyte globulin (RATG) remains a key component of immunosuppressive strategies in transplantation. The human thymus immunization regimen that produces highly immunosuppressive RATG induces unique antibody specificities in the rabbit. Rabbit monoclonal antibodies (RAb MAbs) to human T cell antigens would be of value in the effort to investigate and reproduce the multiple specificities of RATG. We have fused mouse Sp2/0 cells with splenocytes from rabbits immunized with human thymus and have identified 52 rabbit-mouse heterohybridomas which secrete RAb MAbs directed against human lymphocyte surface antigens. The technical aspects of hybridoma isolation, stabilization and characterization are presented. Analysis by flow cytometry, preabsorption and immunoprecipitation suggests that RAb MAb 1A8 IgG may recognize LFA-1, one of the principal lymphocyte surface antigens recognized by RATG. The 1A8 antigen is 180 kDa and is expressed by 80-90% human PBL and thymocytes. LFA-1 and the 1A8 antigen exhibit 100% co-expression in two-color FACS analysis using four different murine anti-LFA-1 MAbs. 1A8 markedly inhibits the mitogenic response of lymphocytes to PHA, as do murine anti-LFA-1 MAbs. A combination of rabbit antilymphocyte MAbs may potentially reproduce the multiple specificities found in polyclonal RATG and lead to the production of a superior immunosuppressive clinical agent. PMID- 8359824 TI - A rapid, simple method for calculating equilibrium constants and antibody site concentrations from dilution curves alone. AB - A rapid new practical method for calculating both the antibody-antigen equilibrium constant and the antibody concentration from antibody dilution curve data alone is described. This method is faster than the inhibition curve method for evaluating a humoral immune response. It is particularly suitable for monitoring the immune response of an immunization program. The response is assessed as an immunization index, Abi*Ka. This index is more exact than the antibody titer obtained from dilution curves and independent of the specific activity of the labelled molecule and total activity used in the assay. The method was used to monitor the production of a monoclonal antibody to the sulphide peptide leucotriene including immunization, cloning and purification. PMID- 8359825 TI - Selection of monoclonal antibodies that bind and inhibit tissue-type plasminogen activator. AB - Three monoclonal antibodies raised against tissue-type plasminogen activator (t PA) were selected for their ability to inhibit solid-phase bound t-PA. Each monoclonal antibody blocked the release of p-nitroaniline from H-D-Ile-Pro-Arg pNA (S-2288). The first antibody 1D2 was a gamma 2b, kappa with KD = 8 x 10(-9) M, the second antibody 2B9 was a gamma 1, kappa with KD = 2 x 10(-9) M, and the third antibody 5A9 was a gamma 1,kappa with KD = 4 x 10(-10) M. In solution-phase format each antibody blocked the conversion of plasminogen to plasmin as judged by a plasmin assay and also inhibited t-PA-mediated lysis of plasma fibrin clot in plasma. The binding of each 125I-radiolabeled antibody to t-PA was inhibited by any one of the three antibodies, suggesting that they recognized a common epitope on t-PA which was absent on unfolded t-PA. We concluded these antibodies bind near t-PA active site since PPACK treatment lowered binding of two antibodies. We believe solid-phase chromogenic substrate assay may be a useful way to screen for antibodies directed against the active site of proteases. PMID- 8359826 TI - An immunofluorescent stain for Helicobacter pylori. AB - We prepared a murine monoclonal antibody that recognized the Helicobacter pylori urease. Monoclonal antibody, U2, reacted with purified native urease in enzyme linked immunosorbent assay but it did not react in Western immunoblot analysis. Urease was immunoprecipitated with U2 bound to Staphylococcus aureus protein A, followed by elution and visualization by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. The species and strain specificity of U2 were determined by biodot reaction with H. pylori, H. mustelae, Campylobacter spp., and other gram negative bacteria. Monoclonal antibody, U2, was used for an indirect immunofluorescent stain of formalin fixed gastric biopsies from patients with H. pylori gastritis. The immunofluorescent stain showed spiral and coccoid forms of H. pylori within the gastric mucosa. U2 was specific for H. pylori and did not react with other tested bacteria. These findings suggest that antibody U2 might be of diagnostic value for specific immunofluorescence detection of H. pylori. PMID- 8359827 TI - The use of a novel immune complex to isolate neutralizing antibodies to basic fibroblast growth factor. AB - This paper describes the use of a novel immune complex (IC) to generate neutralizing monoclonal antibodies to basic fibroblast growth factor. The IC uses a non-neutralizing monoclonal antibody bound to Protein A, itself coated on a solid support, to capture the antigen. Presumably, the capture antibody binds to a region of the antigen distal from the neutralizing site. Animals, immunized with the IC, develop a neutralizing titer and hybridomas producing neutralizing antibodies to basic FGF were obtained. This method can be used to generate neutralizing monoclonals to highly conserved growth factors whenever the antigen can be captured at a site distal to the neutralizing eptiopes. PMID- 8359828 TI - Androgenic regulation of glycolytic and HMP pathway in epididymis and vas deferens of rhesus monkey. AB - The androgenic regulation of the eleven enzymes of glycolytic pathway and two key enzymes of HMP pathway was studied in the initial segment, caput, corpus and cauda regions of the epididymis and in the vas deferens of rhesus monkey. The specific activities of enzymes were expressed as units of activity per mg DNA. Results in control animals indicate a marked difference in energy metabolism of epididymis and vas deferens. However, the epididymal duct itself did not show much regional variation in enzyme activities along its length. All the enzymes of the two pathways studied showed significant reduction after castration, the regulatory enzymes being affected more severely. On treatment with exogenous dihydrotestosterone, most of these enzymes showed stimulation in castrated monkeys, but none of them could be restored to normal level. The stimulation of these enzymes on treatment with exogenous dihydrotestosterone varied along the epididymal duct itself being maximum in the initial segment and minimum in the cauda region. The changes in the vas deferens were less marked as compared to the epididymis following castration and androgen replacement. PMID- 8359829 TI - Potentiation of radiation effects in plateau phase human glioma cells by combination of metabolic inhibitors. AB - Effects of glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on radiation damage were studied in a human glioma cell line (BMG-1), grown to confluence in monolayer. After irradiation (60Co-gamma-rays, 2 Gy) and incubation with low concentrations of 2-DG (0.5, 1.25 mM; 2-DG/glucose = 0.1, 0.25; 2 hr), in the absence or presence of respiratory inhibitor KCN (0.5-2 mM), cells were trypsinized and plated to assay radiation induced cytogenetic damage (micronuclei formation). The observations made were: (1) 2-DG and/or KCN treatments did not induce damage in unirradiated cells. (2) Either of these treatments did not increase radiation induced micronuclei formation. (3) Presence of 2-DG along with KCN (1,2 mM) significantly enhanced the radiation induced micronuclei formation. (4) Preliminary experiments by macrocolony assay showed that radiation induced cell death was also significantly increased by the combined treatment. These observations suggest that presence of clinically feasible, low concentrations of 2-DG (2-DG/glucose < 0.5) for short intervals of time after radiation could increase radiation damage in non-cycling, hypoxic tumour cells with impaired oxidative and increased glycolytic energy metabolism. PMID- 8359830 TI - Anticholestatic effect of picroliv, active hepatoprotective principle of Picrorhiza kurrooa, against carbon tetrachloride induced cholestasis. AB - Picroliv showed a dose (3-12 mg/kg, po for 7 days) dependent choleretic activity as evidenced by increase in bile flow and its contents (bile salts and bile acids). Significant anticholestatic activity was also observed against carbon tetrachloride induced cholestasis in conscious rat, anaesthetized guinea pig and cat. Picroliv was more active than the known hepatoprotective drug silymarin. PMID- 8359832 TI - Testosterone and lipid peroxide metabolism in orchidectomised rats. AB - The effect of testosterone on lipid peroxides and antiperoxidative enzymes in normal and orchidectomised animals has been studied. Orchidectomy results in increased lipid peroxidation in the heart, while administration of testosterone to the animals reverses this to a certain extent. On the other hand the administration of testosterone to normal rats results in increased lipid peroxidation in the liver and heart. PMID- 8359831 TI - Cholesterol side-chain cleavage by immobilized cells of Rhodococcus equi DSM 89 133. AB - Side-chain cleavage of sterol and extracellular cholesterol oxidase activity were investigated using viable cells of R. equi DSM 89-133 immobilized in polyacrylamide gel. In batch culture, immobilized cells were active in side-chain cleavage of cholesterol for more than 30 days. Free or immobilized cells were incapable of side-chain cleavage in the absence of 2,2' dipyridyl; cholesterol oxidase was, however, produced in both the cases. Maximal activity of the immobilized cells was 60 to 70% of the free cells. PMID- 8359833 TI - Effect of leaf extract of Aegle marmelose in diabetic rats. AB - Alloxan induced animal model was used to evaluate the potential antidiabetic effect of A. marmelose leaf extract. The diabetic animals were given insulin injection and another group A. marmelose leaf extract orally. It maintained the weight of the animals near to the control rats but a significant decrease in weight was noted in diabetic animals without any treatment. The blood glucose level in treated animals were near to that of control ones. Also a significantly increased glucose tolerance was observed in animals orally given the leaf extract prior to the experiment. A significant decrease in liver glycogen (1.24 +/- .07 g/100 g of wet tissue) was observed in diabetic rats which was brought to almost the normal level (1.84 +/- .14 g/100 g) with leaf extract treatment. Blood urea and serum cholesterol increased (62.66 +/- 3.50 and 192.67 +/- 13.64 mg/dl) significantly in alloxan diabetic rats. The leaf extract treatment decreased the blood urea and serum cholesterol (37.83 +/- 3.97 and 99.20 +/- 8.43 mg/dl) to that of control ones. A similar effect was seen with insulin treatment. The results indicate that the active principle in A. marmelose leaf extract has similar hypoglycaemic activity to insulin treatment. PMID- 8359834 TI - Effects of gestational undernutrition, stress and diazepam treatment on spatial discrimination learning and retention in young rats. AB - Effects of prenatal undernutrition, stress and diazepam treatment on learning acquisition, and subsequent retention of a spatial discrimination task was assessed in the offsprings. Undernutrition of the dams was induced by restricting food intake to half, throughout the period of gestation, whereas footshock stress and diazepam (0.5 mg/kg, ip) treatment was given from day 13 to 20 of gestation, this being the critical period for neural development in this species. The pups born were subjected to spatial discrimination learning, and retention of the learning acquisition after an interval of one week, in a single unit black/white T-maze, at 8-9 weeks of age. The results indicate that prenatal undernutrition induces significant learning and retention deficits in the offspring, whereas the effect of prenatal stress was limited to only deficit in learning acquisition. Prenatally administered diazepam induced significant deficits in learning acquisition and subsequent retention of the discrimination task in pups culled from normally nourished dams. However, offsprings from diazepam administered undernourished dams exhibited less marked cognitive deficits, which may be attributable to the altered emotional reactivity of pups born to undernourished mothers. Prenatally administered diazepam also induced differential effects in stressed and non-stressed dam offsprings, though the effects were statistically insignificant. The results suggest that prenatal insults, in the form of undernourishment, stress and anxiolytic drugs, leave a lasting imprint on cognitive behaviour of the offspring. The final effect on this behaviour may be determined by the co-existence of these prenatal factors, particularly at a time when the foetus is vulnerable because of neural development and differentiation. PMID- 8359835 TI - Comparative efficacy of exogenous acetylcholinesterase administration on soman and dichlorvos toxicity in rats. AB - Cholinesterase (ChE) activity in the blood serum of rats was elevated to 15, 25, and 45 times by the sc administration of 1000, 2000 and 3000 electric eel acetylcholinesterase (AChE) units respectively. Apparently no ill-effect to animals was observed. The maximal activity of the enzyme occurred in 90 min after its administration and was directly proportional to the administered dose. The increase activity of ChE in the serum on the exogenous administration of AChE persisted for 18 hr. The exogenously raised serum ChE, protected rats against lethal dose of dichlorvos, but not against lethal dose of soman. The possible mechanism of differential response in discussed. PMID- 8359837 TI - Reproductive toxicity of vincristine in male rats. AB - Gross morphological and gravimetric changes were observed in the male reproductive system of sexually mature rats as well as rats in pubertal transition, given a continuous treatment of vincristine at dose levels of 10/20 and 5/10 micrograms respectively per day, for 15 days. The treatment resulted in a drastic regression of entire male reproductive system, suggesting that vincristine would cause male reproductive toxicity. PMID- 8359836 TI - Methyl parathion induced alterations in GABAergic system during critical stage of central nervous system development in albino rat pups. AB - Sublethal doses of methyl parathion (o, o-dimethyl-o-nitrophenyl thiophosphate) injected intraperitoneally to 7th day old developing albino rat pups induced alterations in the inhibitory GABAergic system of CNS. A substantial simulation of the inhibitory system was noticed. A profound increase was found in the level of the inhibitory transmitter, GABA on methyl parathion injection. An increase in the activity levels of the enzymes glutamic acid decarboxylase and 4 aminobutyrate-2-oxoglutarate-amino transferase in the cortex, brain stem and spinal cord of the CNS was found. It is observed that methyl parathion causes potentiation of the inhibitory transmission (GABAergic system) in the wake of inducing suppression of cholinergic system in CNS of developing rat pups. PMID- 8359838 TI - Embryo transfer in rabbits. AB - Surgical method of embryo collection and embryo transfer was used in rabbit. PMSG was used for superovulation. Out of the 41 embryos collected from 6 donors, 30 embryos were transferred in 7 recipients. Out of 7 embryo transferred recipients, 2 kidded giving birth to 7 kids. PMID- 8359839 TI - Antifertility activity of Ailanthus excelsa Linn. in female albino rats. AB - Alcoholic extract of leaf and stem bark of A. excelsa at a dose of 250 mg equivalent of plant material/kg body weight, exhibited remarkably high anti implantation and early abortifacient activities. The results are in agreement with the traditional use of this plant as a abortifacient by the Irula women of the Nilgiri district. PMID- 8359840 TI - Prolactin suppression during pre and post-implantation periods on rat uterine glucosamine synthase activity. AB - Administration of bromocriptine (Bc), an ergot derivative having dopamine receptor agonist activity, to rats on day 1-5 of pregnancy prevented implantation of blastocysts and significantly suppressed uterine glucosamine 6-phosphate synthase activity. There was no effect on implantation or the enzyme activity when Bc was injected on day 7 or later of pregnancy. Injection of prolactin following Bc partially restored the enzyme activity and increased number of implantation sites. These results indicate that suppression of prolactin on day 1 to 5 of pregnancy causes failure of implantation. Bc on day 9 or later had no effect possibly due to the availability of placental LH/hCG to support the luteal cells. PMID- 8359841 TI - Prostaglandin biosynthesis inhibitory activity of some indian-1 acids in relation to their anti-inflammatory activity and ulcerogenic potency. AB - Continuation of our work towards development of some newer non-steroidal anti inflammatory agents led us to some substituted indian-1-acids with low ulcerogenic liability. Prostaglandin biosynthesis inhibitory activity of these indian acids and their acid dissociation constants were evaluated in view of their activity profile. PMID- 8359842 TI - Inhibition of albumin denaturation and anti-inflammatory activity of acetamido [(phenyl-4'-yl)-oxymethyl)]2-(p-substituted phenylamino)-1,2,4-triazoles and 1,3,4-thiadiazoles. AB - Acetamido [(phenyl-4'-yl)-oxymethyl)]-2-(p-substituted-phenylamino)-1,2,4-tr iazoles (4a-4d) and 1,3,4-thiadiazoles (5a-5d) inhibited the thermal denaturation of bovine serum albumin. As protein denaturation is implicated in inflammation, some compounds which showed good inhibition of denaturation were tested in vivo for anti-inflammatory activity by carrageenan induced edema in the rat paw. Although there was no complete correlation, compounds which showed good inhibition of denaturation also showed significant anti-inflammatory activity. PMID- 8359843 TI - Lung injury by furanoterpenoids isolated from Fusarium solani infected sweet potato, Ipomea batatas. AB - Intraperitoneal administration (1 mg/kg body/wt./day for 21 days) of crude extract of furanoterpenoids, isolated from F. solani damaged I. batatas caused pulmonary oedema in albino rats. The elevated broncho alveolar lavage (BAL) angiotensin converting enzyme (ACE), lactate dehydrogenase (LDH) and protein levels indicated lung damage. The estimation of pulmonary extracellular surfactant phospholipids showed an alteration in various phospholipid fractions. PMID- 8359844 TI - Correlation between antiamoebic IgG and autoreactive anti-IgG in amoebic liver abscess cases. AB - IgG isolated and purified from a healthy human serum through Sephadex G-200 and protein A CL 4B sepharose chromatography was used for detection of its own antibodies and correlated with the antiamoebic antibody titres in amoebic liver abscess cases. The mean titres with standard deviation of the self reactive antibodies to serum IgG both ALA cases and healthy controls show a highly significant difference, and antiamoebic antibody titres (IgG) are very much correlated with the autoreactive anti IgG titres in amoebic liver abscess cases. This correlation suggests that as antiamoebic IgG levels reach to its maximum, autoreactive anti IgG are produced to switch off antiamoebic anti IgG production in amoebic liver abscess cases. PMID- 8359845 TI - Effect of thyroxine, prolactin and adrenalin on the gravid ovaries of the frog Rana cyanophlyctis (Schn.). AB - The effects of thyroxine, prolactin and adrenalin on the gravid ovaries of R. cyanophlyctis were studied during late prebreeding period when vitellogenic growth of oocytes is complete or near completion. Specified doses of hormones were injected (ip) six days a week for one month. They were fed guppies ad libitum daily 6 days a week. Administration of 2 or 5 micrograms eltroxine (synthetic thyroxine) had no effect on ovaries or oviducts. Whereas, higher doses 8, 12 and 16 micrograms thyroxine caused significant (P < 0.05) decrease in the per cent weight of ovaries and oviducts. The mean diameter of the largest oocyte was also reduced significantly compared to the controls. There was an increase in the atresia of vitellogenic oocytes. Treatment with 100 micrograms prolactin also caused reduction in the per cent weight of ovaries and oviducts. However, mean diameter of the largest oocyte did not change significantly. Follicular atresia increased only moderately. Injection of 180 micrograms adrenalin bitartrate caused drastic decrease (P < 0.05) in the per cent weight of ovaries and oviducts and mean diameter of the largest oocyte. Many yolky follicles became atretic. The findings suggest that increase in the levels of thyroxine (beyond a certain limit), prolactin and adrenalin around the breeding period decrease the fecundity of the frog by inducing atresia of yolky oocytes. We conclude that the above hormones in excess quantities act as negative modifiers of ovarian activity in R. cyanophlyctis. PMID- 8359846 TI - Effect of (d-Ala6) LHRH on hypophyseal gonadotrophs and ovary of adult frog, Rana tigrina (Daud.) during post-breeding regression phase. AB - Effects of synthetic luteinizing hormone-releasing hormone (LHRH, 1.5 micrograms) agonist on pituitary and ovary were studied in R. tigrina during November, the post-breeding regression phase. Injections (ip) were given 6 days a week for 30 days and frogs were sacrificed on day 31. Pituitary sections were stained with AB PAS-OG. The staining intensity, cytoplasmic granulation and cell, nuclear and cytoplasmic areas of hypophyseal gonadotrophs (B2 cells) increased (P < 0.05) following LHRH administration. In controls, the B2 cells were small and faintly stained. LHRH treatment significantly increased ovarian weight over controls due to recruitment of medium sized second growth phase oocytes (MSGP) from the first growth phase (FGP) oocytes. Nearly 50% of oocytes from the FGP oocyte pool were recruited to SGP. Control frog ovaries lacked SGP oocytes. The results demonstrate that both ovary and pituitary of R. tigrina remain responsive to gonadotrophic and GnRH stimulation respectively during the post breeding regression phase. PMID- 8359847 TI - Modulation in activity of some epididymal glycosidases by prolactin. AB - Activity of glycosidases in the epididymis was influenced by several factors originating in the testis. Activities of all the three glycosidases studied viz., beta-glucosidase, beta-galactosidase and alpha-mannosidase were found to be significantly lower in the epididymis of orchidectomized animals than in sham operated rats. However, an enhanced activity of epididymal beta-galactosidase and alpha-mannosidase was noticed in prolactin treated orchidectomized rats compared to orchidectomized rats given vehicle alone. On the other hand, activity of these two enzymes in bromocriptine treated orchidectomized rats was even lower than that found in orchidectomized rats given vehicle. Neither prolactin nor bromocriptine treatment had any significant influence on the epididymal beta glucosidase. The results suggest a selective but definite action of prolactin on epididymal glycosidases. PMID- 8359848 TI - Photoperiodism in Japanese quail (Coturnix coturnix japonica) with special reference to relative refractoriness. AB - Cloacal gland (an androgen dependent sex accessory) of Japanese quail exhibits full breeding condition as long as these were maintained under long days (LD 16:8). When shifted to short daylength (LD 6:18), scotosensitivity (cloacal gland regression) was observed up to 5 weeks, followed by scotorefractoriness (cloacal gland development). There was a regression in cloacal gland volume of the birds when shifted to intermediate daylength (LD 13.5:10.5 and 13:11) after 12 weeks of exposure to long days (relative refractoriness) but no regression when shifted to relatively short days (< 14 hr) after 3 weeks of exposure to long daylength. Birds maintained under constant short photoperiod (LD 6:18) exhibited cyclicity. Shift experiments (quail reared and maintained under continuous light; LL, were shifted to LD 16:8, 13:11 and 8:16, similarly quail maintained under LD 16:8 were shifted to rest three photoperiods and so on) made to compare the cloacal gland responses indicated that if the difference between two photoperiods (previous and shifted one) was more the percentage of difference in cloacal gland response was also high. Short daylength (LD 8:16) was always gonadoinhibitory for the quail previously exposed to any daylength (13L, 16L or 24L) and 16L and 24L were always stimulatory for the quail previously exposed to other daylength (8L, 13L, 16L). But, when the birds were shifted to 13L, photoresponses cannot be generalized and it depends on the photoperiod to which quail were exposed previously (i.e. photoperiodic history). PMID- 8359849 TI - Reverse single radial immunodiffusion for estimation of titre of anti IgG antibody. AB - Reverse Single Radial Immunodiffusion (SRID) for estimating titre of anti IgG antisera is reported. Unlike the conventional radial immunodiffusion, the antigen (IgG) is held immobile in the gel while the antibody (Anti IgG) diffuses radially from the well (7 microliters) and the diameter of the resulting immuneprecipitates after immunodiffusion at 4 degrees C for 24 hr, represents a linear correlation with the antibody titre. The procedure was standardised by an extensive trial and error employing different concentrations of human IgG in the gel (60-240 micrograms) against varying dilutions of the standard antibody (titre: 3.8 mg/ml). The best results were obtained at 80 micrograms of IgG in the gel. The locally raised rabbit anti IgG antisera displayed a distinctive titre pattern under optimised conditions. Technical reproducibility, high-sensitivity threshold (0.25 mg/ml), simultaneous visual scrutiny of several antibody batches at a glance and ability to assess the shelf life of the stored antisera are its distinct assets. PMID- 8359850 TI - Protective effect of BR-16A (Mentat), a herbal preparation on alcohol abstinence induced anxiety and convulsions. AB - Chronic administration of ethanol (2-5 g/kg, po) on days 1 to 6 and its withdrawal produced anxiogenic reaction in mice and rats as assessed on the elevated plus-maze. Daily administration of BR-16A (100 mg/kg) prior to ethanol intoxication for 6 days prevented withdrawal induced anxiety in both rats and mice. However, acute administration of a single dose of BR-16A, to animals withdrawn from ethanol, i.e. on the 7th day, showed significant anxiogenic response. Ethanol withdrawal also sensitized the convulsogenic reaction to pentylenetetrazole (PTZ). A non-convulsive dose (40 or 60 mg/kg) of PTZ produced full blown convulsions and increased mortality in ethanol withdrawn rats and mice, respectively. Both acute and chronic administration of BR-16A (100 mg/kg) exhibited significant protection against ethanol withdrawal-induced reduction in PTZ threshold in rats and mice. The results suggest the usefulness of this safe herbal psychotropic preparation in the management of ethanol withdrawal reactions. PMID- 8359851 TI - Effect of histaminergic drugs on tail melanophores of tadpole, Bufo melanostictus. AB - The H1 and H2 receptor agonist histamine caused a powerful aggregation of B. melanostictus tail melanophores, which was completely blocked by metiamide, a specific H2 receptor antagonist, while mepyramine an H1 receptor blocker partially blocked the aggregating response. The strong melanin aggregating effect of 4-methyl histamine a specific H2 receptor agonist and its complete blockade by metiamide further supports the conclusion that there exists a dominant population of H2 type of histamine receptors along with sparse population of H1 receptor on the tail melanophores of the toad, which mediate centripetal movement of melanin granules within the pigment cells leading to blanching of the animal. PMID- 8359852 TI - Inhibition of lipid peroxidation by piperine during experimental inflammation in rats. AB - Carrageenin induced rat paw oedema shows a direct co-relationship with liver lipid peroxidation and not with kidney or brain. Pretreatment with piperine or oxyphenylbutazone reduced the liver lipid peroxidation, acid phosphatase and oedema induced by carrageenin. However, no such co-relationship was observed with treatment of these anti-inflammatory agents in control animals. It is, therefore, suggested that the inhibition of these liver enzymes is non specific in nature. PMID- 8359853 TI - Systemic and gastrointestinal candidiasis of infant mice as model for antifungal therapy. AB - Systemic and gastrointestinal infection was established in infant (15-19 days old) mice after oral-intragastric challenge with Candida albicans. All survivors retained high levels of organisms in the liver, kidney, spleen, stomach and intestine up to the 24th post infection day. These animals with persistent infections were used to study the efficacy of short term antifungal therapy. Drug treatment was initiated on 13th day for a two week period, treatment with fluconazole was compared with amphotericin B, and 5 fluorocytosine. The results suggest that fluconazole is a useful drug in the treatment of gastrointestinal candidiasis. PMID- 8359854 TI - Role of lipid peroxides, glutathione and antiperoxidative enzymes in alcohol and drug toxicity. AB - Ethanol administration to rats for 30 days and 90 days followed by paracetamol administration resulted in liver injury indicated by the significant increase in the serum GOT and GPT levels. The ethanol treatment to rats and the administration of paracetamol to the normal and alcoholic rats also caused a significant increase in the activity of serum acid and alkaline phosphatase. The hepatotoxicity of ethanol and paracetamol were indicated by the histological alterations in this study. The content of lipid peroxidation products malondialdehyde, hydroperoxides and conjugated dienes were increased in the liver, heart, kidney and brain of the acute and chronic ethanol treated and paracetamol treated rats. The activities of the antiperoxidative enzymes-SOD and catalase decreased in the ethanol and paracetamol treated rats. The changes in the activities of the antiperoxidative enzymes in alcoholism and drug toxicity suggests increased peroxidation, increased synthesis of ecosonoids and increased damage to the tissues. The glutathione levels were decreased in the rats administered ethanol for 30 days, while the glutathione levels increased in the 90 days ethanol treated rats. The paracetamol treatment caused a decrease in the glutathione levels in the normals and the ethanol treated rats. PMID- 8359855 TI - Oviposition site preference in four species of Drosophila. AB - Oviposition site preference which is an important aspect of nonsexual behaviour of adult females was studied in four species of Drosophila, viz. D. ananassae, D. bipectinata, D. malerkotliana and D. biarmipes. The number of eggs laid by females in food vials was counted for 20 days. In each species, eggs were counted in both central and peripheral areas of culture medium. Eggs were also separated into two groups: deposited on the surface of food medium and inserted into the surface of culture medium. Greater proportion of eggs was oviposited in peripheral area of food medium and were inserted into the surface of the medium by females of all the four species. However, there are interspecies variations with respect to oviposition site preference. Further, these species show variation with respect to total fecundity. D. ananassae lays maximum number of eggs whereas D. biarmipes shows lowest rate of fecundity. PMID- 8359856 TI - Hypoglycaemic activity of arecoline in betel nut Areca catechu L. PMID- 8359857 TI - Recognition of Entamoeba histolytica in liver abscess cases through their specific antiamoebic antibodies. PMID- 8359858 TI - Penicillin decreases streptococcal hydrophobicity and streptococcal adherence to human pharyngeal cells. PMID- 8359859 TI - Control of citrinin caused nephrotoxicosis through aqueous leaf extract of Vitis vinifera L., mercurious corrossivus and cortisone. PMID- 8359860 TI - Geographic distribution of I-R and P-M systems of hybrid dysgenesis in Indian populations of Drosophila melanogaster. PMID- 8359861 TI - Vitamin E as a radioprotector of bursa of Fabricius in chicks. PMID- 8359862 TI - Denervation and exercise effects on cholesterol content of chick pectoralis and gastrocnemii muscles. PMID- 8359864 TI - Induction of experimental autoimmune myasthenia gravis with acetylcholine receptors using a nonionic block copolymer as adjuvant. AB - To induce autoimmune diseases in animals, the auto-antigen has to be emulsified in adjuvants (e.g., complete Freund's adjuvant) containing microbial products such as Mycobacterium tuberculosis. But these powerful immunoadjuvants are not without undesirable immune response to the microbial proteins and induction of adjuvant arthritis, which could interfere with the antigen specific autoimmune response to be tested. This study was performed to evaluate the requirement of microbial products in the induction of experimental autoimmune diseases, and to identify an adjuvant without unwanted immune responses. C57BL/6 mice were inoculated with Torpedo acetylcholine receptors (T-AChR) emulsified in Titermax (TM), an adjuvant containing nonionic block copolymer and no microbial products, and evaluated for experimental autoimmune myasthenia gravis (EAMG) susceptibility. Mice immunized with T-AChR in TM demonstrated characteristic myasthenic muscle weakness with electrophysiological defect, elevated serum anti AChR antibodies, and muscle AChR loss. None of the mice that received TM alone had muscle weakness, serum anti-AChR antibodies or muscle AChR loss. The data imply that microbial products are not critical in the induction of autoimmune diseases like myasthenia gravis in mice. Further, nonionic block copolymer could be an ideal adjuvant in the induction of autoimmune diseases in animals. PMID- 8359863 TI - Effects of various anti-T cell receptor antibodies on the development of type II collagen-induced arthritis in mice. AB - Recent genetic studies of David and coworkers suggest that subsets of T cells utilizing specific V beta TcR genes may play important roles in the susceptibility to collagen-induced arthritis (CIA). Hence, in vivo depletion of such T cell subsets may significantly affect the development of CIA. To address this possibility, we first examined the effects of in vivo treatments with various monoclonal antibodies (mAbs) that are specific for particular TcR V beta families on the induction of CIA. Results presented in this study demonstrated that treatments with either anti-V beta 6, anti-V beta 8 or anti-V beta 11 did not suppress the development of arthritis in collagen-immunized mice. While combined treatments with these V beta specific mAbs which resulted in the in vivo elimination of V beta 6+, V beta 8+ and V beta 11+ T cells were not very effective in preventing the onset of CIA, the severity of the arthritic disease was somewhat reduced in animals that had received the triad of anti-V beta mAbs. By contrast, depletion of T cells expressing the alpha beta receptors by in vivo treatments with a pan anti-alpha beta mAb significantly decreased the incidence of CIA. Therefore, although an effect on the development of CIA was achieved by in vivo treatments with a mAb that detects all alpha beta + T cells, the elimination of only a few subsets of T cells which included the V beta 6+, V beta 8+, and V beta 11+ cells did not profoundly alter the incidence of CIA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359866 TI - Irreversible suppression of CD8 expression in CD4-CD8+ thymocytes upon in vitro stimulation. AB - CD8 (Ly-2) expression was suppressed in purified murine CD4-CD8+ thymocytes at the mRNA level upon continuous stimulation with PMA and ionomycin in the presence of rIL-2. The level of CD8 expression on CD4-CD8+ thymocytes was reduced gradually during the culture and a majority of them turned into CD4-CD8- cells after 48 hr. This suppression was not transient, since CD8 expression was not recovered on these cells in additional 48 hr of culture without PMA and ionomycin. The suppression was dependent on the concentrations of PMA and ionomycin, and inhibited by adding an immunosuppressant, CsA to the culture. Treatment with either PMA or ionomycin alone did not induce suppression of CD8. Crosslinking of CD3-epsilon chains also induced suppression of CD8 for a part of CD4-CD8+ thymocytes. Interestingly, CD8 expression was hardly suppressed in CD4 CD8+ peripheral T lymphocytes, suggesting that the mechanisms of suppression of CD8 is developmentally regulated. We propose that the suppression of CD8 expression at CD4-CD8+ stage involves an additional mechanism of negative selection of thymic T cells. PMID- 8359865 TI - Inhibitory effect of lipopolysaccharide-stimulated P388D1 macrophage-like cells on plasmacytoma cells. AB - Culture supernatants of lipopolysaccharide-stimulated P388D1 macrophage-like tumor cells showed a growth inhibitory effect on plasmacytoma MOPC-315, MPC-11 and myeloma FO cells, but had no effect on J558 plasmacytoma cells. Based on the results of trypan blue staining and a 51Cr release assay, the supernatant had both cytotoxic and cytostatic activity for MOPC-315 plasmacytoma cells. The inhibitory activity was trypsin-sensitive, heat-stable at 100 degrees C for 20 min., but sensitive to 2-mercaptoethanol and cystein HCl. At least 6 hrs of exposure period were required for the P388D1 culture supernatant to show an inhibitory effect on plasmacytoma cells. Since the inhibitory activity could not be blocked by protease inhibitor or neutralized by antibodies to mouse IL-1 beta, IL-6 and TNF-alpha, the inhibitory factor(s) was distinct from the defined cytotoxic factors. After partial purification with DEAE-Sephacel and Sephacryl S 300 chromatography, four major active peaks with the molecular mass of 874-KDa (near the void volume), 112-KDa, 45-KDa and 18-KDa were obtained. PMID- 8359867 TI - In recognition of an implant pioneer: Professor Dr. Andre Schroeder. PMID- 8359868 TI - Is osteoporosis a risk factor for osseointegration of dental implants? AB - The success of osseointegration depends in part on the state of the host bed. Concerns have therefore been raised about osteoporosis, a condition believed to be associated with a decrease in bone quality and quantity. However, the orthopedic literature indicates that osteoporotic fractures heal readily and that the level of bone mass and estimates of the parameters associated with bone remodeling present considerable overlap between patients with osteoporosis and control subjects. It also appears that osteoporosis, as diagnosed at one particular site of the skeleton, is not necessarily seen at another distant site. Although the prevalence of osteoporosis increases among the elderly and after menopause, the results of this study indicate that implant failure rate is not correlated with age and sex. A review of the literature and of results of a series of patients treated does not provide a compelling theoretical or practical basis to expect osteoporosis to be a risk factor for osseointegrated dental implants. PMID- 8359869 TI - Repositioning the inferior alveolar nerve for placement of endosseous implants: technical note. AB - Placement of implants in the posterior mandible is limited by the height of bone between the alveolar crest and the inferior alveolar canal. This paper discusses a surgical technique to reposition and protect the neurovascular bundle so that endosseous implants may be placed. A rectangular window is cut in the cortical bone posterior to the mental foramen. The mental foramen is not violated and the mental nerve is not relieved peripherally into the soft tissue. Cancellous bone is removed from the window and the canal is uncovered. A vessel loop placed around the bundle repositions and protects the nerve laterally. After implant placement, the bundle is replaced within the cortical window and the mucoperiosteal flap is sutured. Avoiding manipulation of the terminal branches of the inferior alveolar nerve reduces the risk of permanent nerve damage. PMID- 8359870 TI - Treatment planning and placement of implants in the posterior maxillae: report of 732 consecutive Nobelpharma implants. AB - One to nine Nobelpharma osseointegrated implants were placed in the posterior maxillae of 213 consecutive partially edentulous patients. Reconstruction was completed with a ceramic fixed partial denture with follow-up of 5 to 70 months (mean 30.3 months) after loading. Thirty-four implants in 29 patients failed; eight were replaced and one of these failed. Thus, the overall failure rate was 4.8% (35/732). The failure rate in type IV bone was only slightly higher than that in types II and III bone (5.5% versus 4.6%). The failure rate in the entire molar area was 5.3% compared with 4.5% in the premolar area (P = NS), and the failure rate of 7-mm implants was 9.5% compared with 3.8% for implants of all other lengths (P = .01). PMID- 8359871 TI - Osseointegrated dental implants with ball attachments supporting overdentures in patients with mandibular alveolar ridge atrophy. AB - Branemark dental implants with ball attachments supporting overdentures were used as alternative treatment to combined lingual-vestibuloplasty with free split thickness skin graft and removable dentures in 25 consecutive patients with mandibular alveolar ridge atrophy. Ninety-three fixtures were placed. Ball attachments were mounted on the fixtures, and implant-supported overdentures were inserted 3 to 4 months after fixture placement. The observation period after implant activation and prosthesis insertion varied from 12 to 27 months with a median observation period of 18 months. The overall success rate of individual implants was 97% (90/93). The prosthesis function rate was 100% (25/25). The 1 year success rate of individual implants was 98% (91/93) with a prosthesis function rate of 100% (25/25). No persistent surgical or prosthodontic complications were observed. Preliminary results indicate that osseointegrated Branemark dental implants with ball attachments supporting overdentures can be a successful alternative to combined lingual-vestibuloplasty with free split thickness skin graft and removal dentures in patients with denture problems related to mandibular alveolar ridge atrophy. PMID- 8359872 TI - Treatment of the severely resorbed maxillae with bone graft and titanium implants: histologic review of autopsy specimens. AB - One of a series of patients with extremely resorbed maxillae treated with bone grafts from the hip in combination with Branemark self-tapping fixtures died in a car accident 4 months after implant surgery. Autopsy specimens from this patient were analyzed to evaluate the amount and extent of "osseointegration" after 4 months of healing. Histologic examination revealed that minimal bone was in direct contact with the titanium and the general pattern was that of soft tissue screw anchorage. There were no signs of sequestering of the transplanted bone. The connection between the nasal cavity and the sinus mucosa with respect to the transplants seemed to be without adverse reactions. The superior part of the transplant did show signs of newly formed bone. The grafted specimens showed indications of delayed bone response compared to the nongrafted situation. All implants were clinically stable as studied postmortem. PMID- 8359873 TI - Qualitative mechanoperception of natural teeth and endosseous implants. AB - The responses of 100 patients to load on Tubingen ceramic implants and natural teeth were analyzed to learn about the facets of qualitative mechanoperception. This approach revealed four factors of mechanoperception: dullness, intensity, localization, and persistence. Dullness, localization, and persistence were discriminated between teeth and implants. Intensity perception, however, depended on load only. PMID- 8359874 TI - Biomechanical considerations of prosthodontic therapy: the urgency of research into alveolar bone responses. AB - The prognosis of natural and implant abutments depends in part on the complementary and/or antagonistic biomechanic and calcium homeostatic functions of the adjacent alveolar bone. Whereas bone morphology is determined by peak strains, strain rates, and strain distributions, infrequent error strains on abutments have a greater impact on the adjacent alveolar bone than those generated during "normal" activity. Alveolar responses depend on the immediate prevailing systemic and local demands, although unexpected abutment failures will continue until such influences have been investigated further. PMID- 8359875 TI - The effect of crestal versus mucobuccal incisions on the success rate of implant osseointegration. AB - A retrospective analysis compared the success rate of osseointegration of Nobelpharma implants at stage 2 surgery. The implants had been placed using either a mucobuccal fold incision or a crestal incision. A total of 386 implants was placed in 92 patients; 265 implants were placed in 60 patients using a mucobuccal fold incision, with a success rate of 98.8%, and 121 implants were placed in 32 patients using a crestal incision, with a success rate of 98.3%. Implants can be placed using either a mucobuccal fold incision or a crestal incision to achieve predictable success. PMID- 8359876 TI - Anatomic consideration for preventive implantation. AB - The aim of preventive implant therapy is to prevent or delay loss of alveolar ridge bone mass. For use in an anatomic study of 60 mandibles, resorption of the alveolar ridge was classified into four preventive stages: (1) after extraction of teeth; (2) after initial resorption; (3) when the ridge has atrophied to a knife-edge shape; and (4) when only basal bone remains. Implantation in stage 3 necessitates removal of the knife-edge ridge to create space for cylindrical implants. Therefore, implantation in stage 2 is advocated to prevent the development of stage 3. The aim of implantation in stage 4 is to prevent total loss of function of the atrophic mandible. PMID- 8359877 TI - Craniofacial osseointegration: the Canadian experience. AB - A survey was undertaken to determine the number of centers in Canada with an active involvement in extraoral osseointegration. It was found that six centers had placed 222 implants in 91 patients in Canada. The individual implant success rates for the Canadian experience were compared with the published Swedish and United States' experience. The Canadian experience is combined with the Swedish and United States' experience to provide retrospective multinational multicenter data. The data given should be viewed as providing trends only and not as definitive expectations of predictable success rates. The success rates are considered likely to change with time as the number of patients treated increases and the duration of follow-up is extended. The mastoid region in nonradiated patients is considered to provide a high degree of predictable individual implant success. The success rates in radiated patients yield far lower success rates, which vary with anatomic location. The criteria for success in using craniofacial implants need to be defined and should reflect the differences between extraoral and intraoral implants. PMID- 8359878 TI - Use of the final denture base for the intermaxillary registration in an implant supported overdenture: technical note. AB - A method of implant-retained overdenture treatment based on the early use of the final denture base during registration of the maxillomandibular jaw relation is described. Using this stable denture base, an accurate recording of jaw relation and an adequate try-in procedure are facilitated without displacement of the base, especially in the situation of an unfavorable flat edentulous mandibular residual ridge. PMID- 8359879 TI - Distal extension removable partial dentures supported by implants and residual teeth: considerations and case reports. AB - The traditional treatment for an edentulous maxilla opposed by a partially edentulous mandible with a complete denture and a distal extension removable partial denture is fundamentally inadequate. Continuing resorption of alveolar bone under the denture base of the removable partial denture causes changes in the occlusal plane. Consequently, overloading of the anterior maxillary region occurs, usually leading to increased bone resorption in the anterior maxillary ridge. Placement of implants beneath the distal extension denture base of the removable partial denture can result in a stable and durable occlusion. Two patients in whom the use of implants combined with a cast metal removable partial denture provided occlusal stability and improved functional comfort are presented. PMID- 8359880 TI - CyaC-mediated activation is important not only for toxic but also for protective activities of Bordetella pertussis adenylate cyclase-hemolysin. AB - Bordetella pertussis adenylate cyclase-hemolysin (AC-Hly), encoded by the cyaA gene, belongs to the RTX family of toxins with extensive glycine-rich repeats in the carboxy-terminal portion. AC-Hly possesses both adenylate cyclase toxic and hemolytic activities that depend on a posttranslational modification mediated by the product of the cyaC gene. An improved system for AC-Hly synthesis and activation in Escherichia coli was developed. The results show that with purified AC-Hly (i) increased expression of the cyaC gene leads to a higher proportion of activated AC-Hly, (ii) the increase in protective activity of the activated recombinant AC-Hly correlates with the increase in its invasive and hemolytic activities, and (iii) the activated recombinant AC-Hly, but not the nonactivated recombinant AC-Hly, is a protective antigen against B. pertussis infection in a murine respiratory model. This suggests that possibly an immunodominant epitope required for protective activity is linked to the CyaC-mediated modification. Surprisingly, the protective and hemolytic activities of activated recombinant AC Hly were lower than those of AC-Hly produced by B. pertussis, while its invasive activity was higher. This indicates that the modification of AC-Hly in B. pertussis and that in E. coli may differ. PMID- 8359881 TI - An OspB mutant of Borrelia burgdorferi has reduced invasiveness in vitro and reduced infectivity in vivo. AB - Most Borrelia burgdorferi strains have two major surface proteins, OspA and OspB. In the present study, we selected from a clonal population of infectious B. burgdorferi an OspB escape mutant, identified the genetic basis for this phenotype, and evaluated its functional activities. Selection with the anti-OspB antibody H614 was performed in vitro in medium and extended in vivo in scid mice. Mutants with a truncated OspB protein were selected at a frequency of 1 x 10(-5) to 3 x 10(-5). After no major rearrangements in DNA were detected, sequence analysis of the mutant's ospAB locus revealed a single base change in the consensus ribosomal binding sequence for ospB and a single nucleotide deletion in the ospB gene itself. The effect of these mutations was reduced expression of a truncated OspB protein. When functional abilities of the wild type and mutant were compared, the mutant had a threefold-lower capacity to penetrate a human endothelium umbilical vein cell monolayer. Infectivity of wild-type and mutant cells for scid mice was evaluated by culturing different organs, and the median infectious dose was calculated. The inoculum of mutant cells for infecting the mice was 30- to 300-fold higher than that of wild-type cells. This study shows that reduced size and expression of OspB are associated with lowered virulence of B. burgdorferi. Selection of mutants that to some degree remain infectious is one approach to defining the role of different surface proteins in the pathogenesis of Lyme disease. PMID- 8359882 TI - Unexpectedly high levels of some presumably protective secretory immunoglobulin A antibodies to dental plaque bacteria in salivas of both caries-resistant and caries-susceptible subjects. AB - The role of salivary antibodies in protection against cariogenic bacteria is actually a matter of debate. Correlation between caries experience and naturally occurring antibodies was extensively investigated. Comparison of salivary antibodies from 21 caries-resistant and 22 caries-susceptible subjects was carried out by using a new quantitative method. Secretory immunoglobulin A (S IgA) antibodies to Streptococcus sobrinus and Streptococcus sanguis cells were detected in all salivas and at similar levels in both groups. When assayed with two major antigens from S. sobrinus, i.e., protein antigen I/II and cell wall carbohydrates, only specific activities of antibodies to the protein component were increased (P < 0.01), but this occurred unexpectedly in the caries susceptible group. Western blot (immunoblot) analysis with the culture supernatant and cell wall proteins from S. sobrinus showed the same antibody specificity in both groups. No selective increase of the protease-resistant S IgA2 subclass was found, and avidities of antibodies to both antigen I/II and cell wall carbohydrates were similar. Our results demonstrate that naturally induced S-IgA antibodies against S. sanguis, S. sobrinus, and the major antigens of the latter are not sufficient to inhibit caries development. PMID- 8359883 TI - Toxic effects of tetanus toxin on GG2EE macrophages: prevention of gamma interferon-mediated upregulation of lysozyme-specific mRNA levels. AB - By using a nonneuronal cell system, evidence has previously been provided that tetanus toxin (TT) intoxication occurs in macrophages, impairing their secretory activity as well as their antitumoral activity. In particular, both secreted and total lysozyme (LZM) activities are reduced by TT treatment, provided that GG2EE macrophages have been preexposed to gamma interferon (IFN-gamma). In an attempt to provide insight into the molecular mechanisms underlying this phenomenon, we focused our attention on the levels of LZM-specific transcripts. GG2EE macrophages preexposed to IFN-gamma exhibited augmented levels of LZM-specific mRNA. Such an effect was detected 1 h after removal of IFN-gamma, peaked at 3 h, and gradually decreased with time in culture. Exposure of IFN-gamma-pretreated GG2EE macrophages to TT resulted in the prevention of the IFN-gamma-mediated upregulation of LZM mRNA levels. The phenomenon was mediated by the holotoxin (> or = 1 micrograms/ml) and abrogated by preexposure of the macrophages to the C fragment of TT. Protein kinase C (PKC) and Ca(2+)-calmodulin-dependent PK were likely involved in the IFN-gamma-mediated upregulation of LZM mRNA levels and biological activity, as assessed by PK inhibitors. Furthermore, PK inhibitors mimicked TT in impairing LZM activity of GG2EE macrophages, thus suggesting that impairment of PKC and/or the Ca(2+)-calmodulin-dependent PK pathway(s) may be one of the events involved in TT intoxication of macrophages. PMID- 8359884 TI - Stimulation of DNA synthesis in osteoblast-like MC3T3-E1 cells by Bordetella bronchiseptica dermonecrotic toxin. AB - We investigated the effects of Bordetella bronchiseptica dermonecrotic toxin on DNA synthesis in MC3T3-E1 cells. The rate of [methyl-3H]thymidine incorporation increased in the toxin-treated cells more than 24 h after addition of the toxin under the serum-starved conditions. This effect was dependent on the toxin concentration ranging from 0.3 to 3 ng/ml and was eliminated by aphidicolin and hydroxyurea, inhibitors for DNA replication. In the toxin-treated culture, the number of cells did not increase but polynucleated cells appeared and their number increased to ca. 50% of the total number of cells 6 days after the toxin addition. From these results, we concluded that the toxin stimulates DNA replication in MC3T3-E1 cells without cell proliferation. PMID- 8359885 TI - OmpC is involved in invasion of epithelial cells by Shigella flexneri. AB - Osmoregulation of the Shigella flexneri ompC gene and the role of OmpC in Shigella virulence have been investigated. OmpC was highly expressed when bacteria were grown in medium of either low or high osmolarity. This constitutive expression is in contrast with the regulation observed in Escherichia coli, in which the expression of OmpC is repressed at low osmolarity and induced at high osmolarity. In addition, the Shigella ompC gene was barely expressed by a delta ompB (delta ompR and delta envZ) mutant. We described in a previous report that such a mutant was severely impaired in virulence both in vitro and in vivo. Starting from this observation, and in order to assess which gene(s) regulated by ompR and envZ are involved in virulence, we constructed an S. flexneri delta ompC mutant. Three S. flexneri mutants, ompF'-lacZ, delta ompC, and delta ompB, were compared for virulence. The ompF'lacZ mutant behaved like the S. flexneri serotype 5 wild-type strain M90T in all in vitro and in vivo virulence tests. On the contrary, the delta ompB and delta ompC strains were considerably impaired in their virulence phenotypes. The ability of these two mutants to spread from cell to cell and to kill epithelial cells was severely affected. Consequently delta ompC, as previously described for delta ompB, was unable to elicit a positive Sereny test. The delta ompB mutant was restored to virulence by introducing a recombinant multicopy plasmid carrying the cloned E. coli ompC gene, indicating that a functional OmpC protein was necessary and sufficient to restore virulence to this mutant of S. flexneri. PMID- 8359886 TI - Involvement of the stage-specific 82-kilodalton adhesion molecule of Trypanosoma cruzi metacyclic trypomastigotes in host cell invasion. AB - This study provides several pieces of evidence indicating that 3F6-Ag, identified by monoclonal antibody (MAb) 3F6 as a stage-specific glycoprotein of approximately 82 kDa on the surface of metacyclic trypomastigotes of different Trypanosoma cruzi strains, promotes the entry of parasites into host cells through a ligand-receptor type interaction. First, invasion of Vero cells by metacyclic trypomastigotes of both CL and Tulahuen strains was significantly inhibited by MAb 3F6 or its Fab fragments. Second, purified 3F6-Ag bound to Vero cells in a dose-dependent and saturable fashion. Third, soluble 3F6-Ag reduced the infection of Vero cells by metacyclic forms of CL and Tulahuen strains by 90 to 97 and 50%, respectively. Unrelated proteins, as well as extracellular matrix components, such as heparan sulfate and collagen, had no effect. Our studies also show that in the Tulahuen strain, 10D8-Ag, a 35/50-kDa glycoprotein identified by MAb 10D8, participates in target cell invasion, confirming previous observations, but the variant form of 10D8-Ag expressed by highly invasive CL strain metacyclic trypomastigotes appears to be irrelevant. Overall, our results indicate that the surface components of T. cruzi metacyclic trypomastigotes involved in the process of host cell penetration are developmentally regulated molecules, such as 3F6-Ag and 10D8-Ag, that have no counterpart in blood- or tissue culture-derived trypomastigotes. PMID- 8359887 TI - The Mycobacterium leprae antigen 85 complex gene family: identification of the genes for the 85A, 85C, and related MPT51 proteins. AB - The genes for two novel members (designated 85A and 85C) of the Mycobacterium leprae antigen 85 complex family of proteins and the gene for the closely related M. leprae MPT51 protein were isolated. The complete DNA sequence of the M. leprae 85C gene and partial sequences of the 85A and MPT51 genes are presented. As in M. tuberculosis, the M. leprae 85A, 85C, and previously identified 85B component genes are not closely linked on the genome. However, the MPT51 genes of both species localize close to the respective 85A component genes. Like the 85B component, the M. leprae 85A-MPT51 and 85C antigens are recognized by T cells from healthy contacts and leprosy patients. PMID- 8359888 TI - Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans. AB - The gene ECE1 (extent of cell elongation 1) was isolated by differential hybridization screening of a Candida albicans cDNA library by using probes derived from populations of yeast cells or hyphae. Expression of this gene was not detected when C. albicans grew as a budding yeast cell but was observed within 30 min after cells had been induced to form hyphae. In all strains tested, regardless of the induction signal, ECE1 expression correlated with the extent of cell elongation. The genomic version of ECE1 was cloned and sequenced. The deduced 271-amino-acid polypeptide consisted of eight tandem repeats of a degenerate 34-amino-acid sequence which contained no discernible homology with other known sequences. An ECE1 null mutant displayed no morphological alterations, which demonstrated that ECE1 is not essential for cell elongation or hypha formation despite the strict morphological association of its expression. PMID- 8359889 TI - Role of complement component C1q in phagocytosis of Listeria monocytogenes by murine macrophage-like cell lines. AB - Listeria monocytogenes is a facultative intracellular pathogen of a great variety of cells. Among them, macrophages constitute the major effector cells of listerial immunity during the course of an infection. Although the molecular bases of L. monocytogenes attachment and entry to phagocytes are not completely understood, it has been demonstrated that C3b significantly increases L. monocytogenes uptake by macrophages via complement receptor type 3. The first component of complement, C1q, is present in organic fluids at a relatively high concentration, and C1q receptor sites in macrophages are also abundant. In the present report, results of studies on the role of C1q in the internalization and infectivity of L. monocytogenes by macrophages are presented. L. monocytogenes uptake is enhanced by prior treatment of bacteria with normal sera. Heated serum or C1q-deficient serum abrogates this enhancement. Purified C1q specifically restored uptake. This effect was blocked by the addition of F(ab')2 anti-C1q antibody but not by an irrelevant matched antibody. Direct binding of C1q to L. monocytogenes was specific, saturable, and dose dependent with both fluorescent and radiolabeled C1q. N-Acetyl-D-alanyl-L-isoglutamine, diaminopimelic acid, and L-rhamnose caused a significant dose-dependent inhibition of C1q binding to bacteria, suggesting that these molecules, at least, are involved in the attachment of C1q to L. monocytogenes cell wall. When C1q binding structures on macrophage-like cells were blocked with saturating concentrations of C1q, the uptake of C1q-opsonized bacteria was less than in untreated cells. These experiments demonstrate that, in addition to other reported mechanisms, L. monocytogenes binds C1q, which mediates enhanced uptake by macrophages through C1q binding structures. PMID- 8359890 TI - Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids. AB - The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, the O-SPs were not immunogenic in mice. Conjugates of these O SPs, injected into young outbred mice subcutaneously as saline solutions containing 2.5 micrograms of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 micrograms of these conjugates into adult volunteers elicited mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and adsorption of the conjugates onto alum did not enhance their immunogenicity. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization antibodies of the three immunoglobulin classes were similar to or higher than those of recruits in the Israel Defense Force following shigellosis caused by S. flexneri type 2a or S. sonnei. These data provide the basis for evaluating these conjugates to prevent shigellosis. PMID- 8359891 TI - Structural analysis of the Actinobacillus pleuropneumoniae-RTX-toxin I (ApxI) operon. AB - Actinobacillus pleuropneumoniae-RTX-toxin I (ApxI), an important virulence factor, is secreted by serotypes 1, 5, 9, 10, and 11 of A. pleuropneumoniae. However, sequences homologous to the secretion genes apxIBD of the ApxI operon are present in all 12 serotypes except serotype 3. The purpose of this study was to determine and compare the structures of the ApxI operons of the 12 A. pleuropneumoniae serotypes. We focused on the nucleotide sequence comparison of the ApxI-coding genes, the structures of the ApxI operons, and the transcription of the ApxI operons. We determined the nucleotide sequences of the toxin-encoding apxICA genes of serotype 9 and found that the gene for the structural toxin, apxIA, was almost identical to the apxIA gene of serotype 1. The toxin-encoding genes of the other serotypes are also similar for the main part; nevertheless, two variants were identified, one in serotypes 1, 9, and 11 and one in serotypes 5 and 10. The two apxIA variants differ mainly within the distal 110 nucleotides. Structural analysis demonstrated that intact ApxI operons, consisting of the four contiguous genes apxICABD, are present in serotypes 1, 5, 9, 10, and 11. ApxI operons with a major deletion in the apxICA genes are present in serotypes 2, 4, 6, 7, 8, and 12. Serotype 3 does not contain ApxI operon sequences. We found that all ApxI operons are transcriptionally active despite the partial deletion of the operon in some serotypes. The implications of these data for the expression and secretion of ApxI and the other Apx-toxins, ApxII and ApxIII, as well as for the development of a subunit vaccine against A. pleuropneumoniae will be discussed. PMID- 8359892 TI - Association of type II immunoglobulin G-binding protein expression and survival of group A streptococci in human blood. AB - Expression of immunoglobulin G (IgG)-binding proteins on group A streptococcus strain 64 was monitored on bacteria subjected to sequential passage in human blood. After approximately 10 cycles through human blood, strain 64 demonstrated enhanced levels of IgG-binding protein, including the expression of a type IIa binding molecule with an M(r) of approximately 47,000 present only at very low levels on the parent isolate. Changes in the expression of IgG-binding proteins after passage in human blood were similar to those observed when the same organism was passaged sequentially intraperitoneally in mice. Strain 64, passaged in human blood 23 times, was found to be more virulent than the parent isolate when used to infect mice either intraperitoneally or in a skin air sac. These findings suggest that the expression of IgG-binding proteins may be a common response of group A organisms to pressures exerted by distinct host defense mechanisms. PMID- 8359893 TI - Inactivation of the streptococcal erythrogenic toxin B gene (speB) in Streptococcus pyogenes. AB - Streptococcal proteinase precursor (SPP) is a zymogen secreted by Streptococcus pyogenes that becomes activated to a cysteine proteinase. SPP has been shown to be immunologically identical to streptococcal erythrogenic toxin B (SPE B), and sequence comparison has shown a high degree of homology between the two proteins. In this study, we have constructed a speB mutant strain of S. pyogenes by insertional inactivation. An internal fragment of the cloned speB gene in plasmid pCR1000 was replaced with an erythromycin resistance determinant, and the recombinant plasmid was introduced into strain NZ131 by electrotransformation. Following the selection of erythromycin-resistant clones, Southern hybridization experiments confirmed the presence of the recombinant plasmid containing the erm gene in the chromosome of the resistant strains. Analysis of extracellular proteins produced by the wild-type and speB mutant strains by Ouchterlony immunodiffusion and isoelectric focusing revealed the presence of SPE B in the wild-type strain but not the speB mutant. Additionally, SPP, which has an isoelectric focusing pattern similar to that of SPE B and reacts with SPE B antiserum, was not detected among the extracellular proteins of the speB mutant strain. Proteinase activity as assayed by two different methods was present in the extracellular proteins produced by the wild-type strain, but the speB mutant strain had no extracellular proteinase activity. The mutant strain had a growth rate similar to that of the wild-type strain and produced normal levels of other extracellular products, suggesting that proteinase was not essential for viability as previously suggested. Our data are consistent with the view that a single gene (speB) produces a single protein that has been identified and/or assayed as either SPE B or SPP. PMID- 8359894 TI - Gamma interferon response in secondary Leishmania major infection: role of CD8+ T cells. AB - CD8+ T cells have been shown to contribute to the rapid resolution of secondary lesions developing in immune mice challenged with Leishmania major. In the present study, we assessed directly the participation of specific CD8+ T cells in the memory response induced in immune mice by reinfection. Lymphocyte populations from reinfected immune mice exhibit marked secondary gamma interferon (IFN-gamma) responses. The participation of IFN-gamma-producing CD8+ T cells in the memory response elicited by secondary infectious challenge was demonstrated in both genetically resistant immune CBA mice and genetically susceptible immune BALB/c mice that were rendered resistant by administration of anti-CD4 monoclonal antibody in the early phase of the primary infection. The protective function of CD8+ T cells in experimental murine cutaneous leishmaniasis might thus be explained in part by their ability to secrete IFN-gamma. In this context, the neutralization of IFN-gamma at the time of reinfection reduced the Leishmania specific delayed-type hypersensitivity response, showing that this cytokine is involved in the recall of immunological memory to L. major in vivo. PMID- 8359895 TI - Analysis of cytokine mRNA expression in Listeria-resistant C57BL/6 and Listeria susceptible A/J mice during Listeria monocytogenes infection. AB - This laboratory previously reported that mRNA expression for many cytokines, as determined by reverse transcription-polymerase chain reaction analysis, is induced rapidly in the spleen during murine listeriosis. In the present study, the patterns of cytokine mRNA expression in spleens and livers of Listeria resistant C57BL/6 and Listeria-susceptible A/J mice were compared. In addition, in situ hybridization was performed to evaluate the distributions of cytokine mRNA-expressing cells in these tissues. Listeria-resistant C57BL/6 mice demonstrated greater expression of gamma interferon (IFN-gamma) and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNAs in the spleen than Listeria susceptible A/J mice. Greater numbers of cells expressing IFN-gamma and GM-CSF mRNAs were observed by in situ hybridization in the spleens of C57BL/6 mice than in those of A/J mice. C57BL/6 and A/J mice did not differ in their expression of IFN-gamma mRNA in the liver. Nor did C57BL/6 and A/J mice differ in their expression of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL 2, IL-4, or IL-6 mRNA in the liver or spleen, as determined by reverse transcription-polymerase chain reaction and in situ hybridization. These results indicate that the greater resistance of C57BL/6 mice to Listeria monocytogenes infection is associated with greater expression of IFN-gamma and GM-CSF mRNAs in the spleen and GM-CSF mRNA in the liver. PMID- 8359896 TI - Intracytoplasmic growth and virulence of Listeria monocytogenes auxotrophic mutants. AB - The intracellular growth of several auxotrophic mutants of Listeria monocytogenes was examined in cell culture, and virulence was evaluated in mice by intravenous injection of log-phase bacteria. L. monocytogenes transposon insertion mutants requiring either uracil, phenylalanine, glycine, proline, or nicotinic acid for growth were fully virulent and grew similarly to the parental strain as shown by their growth rates in cell culture. Those requiring all three aromatic amino acids (phenylalanine, tryptophan, and tyrosine) or adenine were 1.5 log10 less virulent than the wild type. A threonine auxotroph, which showed enhanced growth in the presence of threonine-containing peptides as compared with that in the presence of free threonine, was approximately 1 log10 less virulent than the wild type. When host cells were deprived of specific amino acids required by both the host cell and L. monocytogenes, the bacteria continued to grow intracellularly. These studies suggest that the cytoplasm of eucaryotic cells behaves like rich medium, facilitating the growth of an intracellular bacterial pathogen with complex growth requirements. In addition, results related to amino acid deprivation during intracellular growth and specific extracellular growth requirements of a threonine auxotroph suggest that L. monocytogenes may utilize intracellular peptides as a source of amino acids. PMID- 8359897 TI - Interaction of group B streptococcal opacity variants with the host defense system. AB - Group B streptococci (GBS) demonstrate high-frequency phase variation of colony opacity. Colony opacity is a function of chain length, with opaque colonies consisting of GBS that form longer chains. Because opaque variants do not grow on standard streptococcal media, the role of opacity variation in GBS infection has not been studied. We have isolated stable variants from type III GBS that are either transparent (variants 1.2 and 1.3) or opaque (variants 1.1 and 1.5). In this study, we evaluated the interactions of these variants with different components of the host immune system both in vitro and in vivo. Opaque GBS were less immunogenic than transparent GBS. Opaque GBS were more susceptible to killing by polymorphonuclear neutrophils (PMNs) and could induce a chemiluminescent response of PMNs in the absence of antibody (Ab) or complement. Transparent GBS did not induce neutrophil chemiluminescence in the absence of Ab and complement. However, in the presence of Ab and complement, transparent GBS induced a stronger chemiluminescent response than did opaque GBS. Scanning electron micrographs of PMNs and GBS demonstrated differences in the attachment and engulfment of the different variants by the PMNs as well as different effects of the GBS on the PMNs themselves. Interactions with complement were affected by GBS opacity as well, with opaque variant 1.1 initiating complement activation in the absence of any Ab. The virulence of the GBS opacity variants was studied in vivo by inoculation of graded numbers of GBS into newborn mice. Transparent variants 1.2 and 1.3 were most virulent, with variant 1.1 intermediate and variant 1.5 minimally virulent. However, in mixed infections, variant 1.5 greatly enhanced the virulence of small numbers of transparent GBS. These results indicate that the opacity status of GBS can influence the interaction between the GBS and the host immune system. PMID- 8359898 TI - Natural killer cells do not play a dominant role in CD4+ subset differentiation in Candida albicans-infected mice. AB - The effects of in vivo administration of monoclonal antibodies against NK-1.1 bearing cells on the early production of gamma interferon (IFN-gamma) in vitro and development of Th1-associated immunity were studied in mice infected with a live vaccine strain of Candida albicans. At 1 and 4 days postinfection, natural killer (NK) cell-enriched fractions from the spleens of antibody-treated mice displayed a dramatic reduction in 5E6+ lymphocytes and negligible anti-YAC-1 cytotoxic activity in vitro. Nevertheless, the frequency of IFN-gamma-producing cells in those fractions was reduced by less than half, on average, by anti-NK 1.1 treatment in vivo. In addition, the antibody-treated and infected mice demonstrated unchanged T helper cell responses, as measured by yeast-specific footpad reactions, resistance to reinfection, occurrence of antibodies of different isotypes, and production in vitro of interleukin-2 (IL-2), IFN-gamma, IL-4, and IL-10 by CD4+ cells. Therefore, although NK cells may contribute to early IFN-gamma production in Candida-vaccinated mice, these cells apparently do not play a dominant role in the qualitative development of yeast-specific T helper responses. PMID- 8359899 TI - Implication of phagosome-lysosome fusion in restriction of Mycobacterium avium growth in bone marrow macrophages from genetically resistant mice. AB - The ability of the host to resist infection to a variety of intracellular pathogens, including mycobacteria, is strongly dependent upon the expression of the Bcg gene. Mouse strains which express the resistance phenotype (Bcgr) restrict bacterial growth, whereas susceptible strains (Bcgs) allow bacterial growth. Expression of the Bcg allele is known to influence the priming of host macrophages (M phi s) for bactericidal function. In the present work, bone marrow derived M phi s from congenic BALB/c (Bcgs) and C.D2 (BALB/c.Bcgr) mice were infected with the virulent strain Mycobacterium avium TMC 724 to define the mechanism involved in growth restriction of M. avium. By combining CFU measurements and ultrastructural analyses, we show that growth of this bacterium is restricted in marrow M phi s from resistant mice. Using acid phosphatase as a lysosomal marker, we provide evidence that the hydrolytic activity of M phi s, as measured by the capacity of lysosomes to fuse with and transfer active hydrolytic enzymes to phagosomes in which M. avium resides, is an expression of the Bcg gene and that this phenomenon is a key antibacterial activity responsible for growth restriction of M. avium: (i) the percentage of phagosome-lysosome fusions was twice as high in Bcgr M phi s as in Bcgs M phi s, and (ii) the percentage of intact viable bacteria residing in acid phosphatase-negative phagosomes was twice as low in Bcgr M phi s as in the Bcgs counterparts. These differences are not due to a lower activity of the enzyme in Bcgr M phi s. The mechanism by which the Bcg gene exerts control over the phagolysosomal fusion is discussed. PMID- 8359900 TI - Acquired immunity in experimental murine aspergillosis is mediated by macrophages. AB - A number of studies have substantiated the pivotal role of innate defense mechanisms in protection against invasive aspergillosis. However, experiments demonstrating increased resistance to lethal intravenous (i.v.) infection with Aspergillus fumigatus conidia in cortisone-treated or untreated mice preinfected with a sublethal dose of conidia and protection of turkeys inoculated subcutaneously with a killed A. fumigatus germling vaccine against subsequent aerosol challenge led us to speculate that acquired immunity may also contribute to host defense against Aspergillus infection. Five-week-old male BALB/c mice were inoculated i.v. with 1.0 x 10(4) viable conidia or saline and challenged i.v. with 1.0 x 10(6) conidia after 7, 15, or 21 days. No protection against challenge was found after 7 days. However, significant and reproducible protection was observed after 15 and 21 days. Mortality was reduced from 90% in control mice to 53% in preinfected mice 40 days after challenge (P = 0.0002). Increased survival was correlated with decreased content of chitin in lungs, liver, and kidneys 4 and 7 days after challenge (P < 0.05). Mice were again inoculated with 1.0 x 10(4) conidia or saline, and after 21 days, 1.0 x 10(8) or 2.0 x 10(8) splenocytes were transferred to naive syngeneic recipients; 2.0 x 10(8) immune splenocytes conferred significant protection (P = 0.0001) against i.v. challenge with 1.0 x 10(6) conidia, and mortality decreased from 83 to 48% 40 days after challenge. Transfer of immune serum offered no protection despite the presence of antibody against a hyphal homogenate of A. fumigatus, which was absent in the sera of control mice. Protection by immune splenocytes was maintained after selective depletion of T cells but was abolished after removal of plastic-adherent splenocytes. Adherent cells were characterized as macrophages by using morphological criteria, nonspecific esterase, and MAC-1 monoclonal antibody. Production of hydrogen peroxide by peritoneal and splenic macrophages from preinfected mice was the same as and lower than, respectively, that from uninfected controls. However, phagocytosis of conidia by peritoneal or splenic macrophages from mice preinfected i.v. or intratracheally was significantly increased after 2 and 3 h of coculture compared with that from uninfected animals, whereas in vitro killing of conidia by splenic macrophages was unaltered. Peritoneal or splenic macrophages from control or preinfected mice failed to kill hyphae in vitro. Killing of hyphae by polymorphonuclear leukocytes was not significantly different between mice preinfected i.v. and uninfected controls. Taken together, the results indicate that acquired immunity mediated by activated macrophages can be demonstrated in experimental murine aspergillosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8359902 TI - Role of the Streptococcus mutans gtf genes in caries induction in the specific pathogen-free rat model. AB - The role of each of the Streptococcus mutans gtf genes coding for glucan synthesis in cariogenesis was evaluated by using strain UA130 in the specific pathogen-free (SPF) rat model system. Mutants defective in either or both of the genes required for insoluble glucan synthesis, the gtfB and gtfC genes, exhibited markedly reduced levels of smooth-surface carious lesions relative to that of the parental organism. Likewise, the mutant defective in the gtfD gene coding for the glucosyltransferase-S enzyme synthesizing water-soluble glucans also produced significantly fewer smooth-surface lesions than strain UA130. None of these mutations markedly altered the rate of sulcal caries induction relative to that of the parental organism. In addition, a mutant of strain UA130 defective in the gtfA gene was reexamined in the SPF rat model. In contrast to previous results from a gnotobiotic rat system, these mutants also induced significantly fewer smooth-surface carious lesions compared with that by strain UA130. These results suggest that all four genes are important for smooth-surface caries formation. Furthermore, these results are discussed relative to the differences in the diets utilized in the SPF and gnotobiotic rat model systems for assessing the virulence factors of S. mutans. PMID- 8359901 TI - Characterization of Ehrlichia risticii binding, internalization, and proliferation in host cells by flow cytometry. AB - The binding, internalization, and proliferation of Ehrlichia risticii in P388D1 cells and equine polymorphonuclear (PMN) leukocytes were studied by immunofluorescent staining and flow cytometric analysis. The binding of ehrlichiae to P388D1 cells at 4 degrees C was dose dependent, and the antigens of bound organisms were susceptible to pronase treatment. Additionally, the binding of ehrlichiae to P388D1 cells was diminished when either P388D1 cells or ehrlichiae were treated with 1% paraformaldehyde for 30 min or 0.25% trypsin for 15 min. These results indicate that the ehrlichial ligand and host cell receptor are likely surface proteins. Following incubation at 37 degrees C, bound E. risticii and/or its antigens were removed with pronase and indirect immunofluorescent staining in the presence of saponin was used to examine intracellular ehrlichiae. Our results indicate that E. risticii was internalized into P388D1 cells within 3 h and proliferated by 48 h of incubation. The microfilament-disrupting agent cytochalasin D and the transglutaminase inhibitor monodansylcadaverine were used to differentiate between phagocytosis (sensitive to cytochalasin) and receptor-mediated endocytosis (sensitive to monodansylcadaverine) of E. risticii by P388D1 cells. In concentrations that produced distinctive morphological changes and inhibited phagocytosis of polystyrene latex beads, cytochalasin D did not suppress the infectivity of E. risticii. Binding, internalization, or proliferation of E. risticii was not affected by cytochalasin D. However, monodansylcadaverine inhibited infection of E. risticii in a dose-dependent manner. The agent did not affect the attachment of ehrlichiae to host cells, but it did suppress internalization and proliferation. These results suggest that E. risticii is internalized by receptor mediated endocytosis and that productive infection by E. risticii does not depend on phagocytosis by the P388D1 cells. Although E. risticii did not bind to the surface of equine PMN leukocytes at 4 degrees C, organisms were taken up by this cell at 37 degrees C. E. risticii, however, failed to survive in equine PMN leukocytes. PMID- 8359903 TI - Effect of endothelial cells on phagocyte-mediated anticryptococcal activity. AB - The anticryptococcal activity of peripheral blood polymorphonuclear leukocytes (PMN) and monocytes was compared on plastic versus human umbilical vein endothelial cell surfaces. Various amounts of PMN and monocytes were incubated on plastic or endothelial surfaces and then challenged for 18 h with Cryptococcus neoformans. Both phagocyte populations exhibited significantly more anticryptococcal activity on an endothelial cell monolayer than on plastic. Prestimulating the endothelial cell monolayer with interleukin-1 augmented the antifungal activity of PMN but not that of monocytes. In the absence of phagocytes, endothelial cells lacked activity. Blocking antibodies directed against endothelial adhesion molecules ICAM-1 and ELAM-1 did not affect PMN mediated inhibition of fungal growth. Recombinant interleukin-1 and interleukin-8 (two cytokines secreted by endothelial cells) activated neutrophils for modestly enhanced antifungal activity. However, supernatants derived from endothelial cells, as well as neutralizing antibodies directed against the endothelial cell derived cytokines interleukin-8 and granulocyte-macrophage colony-stimulating factor failed to augment PMN antifungal activity. PMN viability after 18 h was diminished on plastic compared with endothelial surfaces. While the percentages of C. neoformans bound to neutrophils were similar on both surfaces, the patterns of binding were markedly different: on endothelial (but not plastic) surfaces, most cryptococci were surrounded by greater than five PMN. Thus, phagocyte mediated inhibition of cryptococcal growth is enhanced on endothelial monolayers compared with plastic surfaces, possibly as a result of differences in phagocyte viability and patterns of binding. Bolstering the activity of circulating phagocytes by stimulating endothelial cells may be of relevance in the treatment of patients with or at risk for cryptococcemia. PMID- 8359904 TI - Virulence of enterohemorrhagic Escherichia coli O91:H21 clinical isolates in an orally infected mouse model. AB - Escherichia coli K-12 strains producing high levels of Shiga-like toxin type II (SLT-II) but not SLT-I were previously shown to be virulent in an orally infected, streptomycin-treated mouse model. In this investigation, we tested the virulence of several SLT-II-producing enterohemorrhagic E. coli (EHEC) isolates from patients with hemorrhagic colitis or hemolytic uremic syndrome. All of the strains tested were able to colonize the mouse intestine. However, only two strains were consistently virulent for mice: O91:H21 strain B2F1 (Strr), which was previously shown to carry two copies of slt-II-related toxins, and O91:H21 strain H414-36/89 (Strr), which was found in this study to contain three genes from the slt-II group. The oral 50% lethal doses of strains B2F1 (Strr) and H414 36/89 (Strr) when fed to streptomycin-treated mice were less than 10 bacteria. Histological sections from moribund mice fed the O91:H21 strains demonstrated extensive renal tubular necrosis; however, hematological results were not consistent with a diagnosis of hemolytic uremic syndrome. The central role of SLT in the virulence of the O91:H21 EHEC strains was supported by the finding that streptomycin-treated mice preinoculated with monoclonal antibody specific for SLT II survived oral challenge with either B2F1 (Strr) or H414-36/89 (Strr). The basis for the variation in virulence among the SLT-II-producing EHEC strains tested was not determined. However, a correlation between the capacity of an EHEC strain to grow in small intestinal mucus and lethality in the streptomycin treated mice was observed. PMID- 8359905 TI - Borrelia burgdorferi outer surface lipoproteins OspA and OspB possess B-cell mitogenic and cytokine-stimulatory properties. AB - Sonicated Borrelia burgdorferi was previously reported to possess both B-cell mitogenic and interleukin-6 (IL-6) stimulatory activities. In this report, two outer surface lipoproteins, OspA and OspB, were purified from B. burgdorferi and assessed for the presence of these functions. OspA was purified from two strains, an OspB-deficient variant of HB19 and N40, while OspB was purified from the N40 strain. All lipoprotein preparations were free of endotoxin contamination, and polymyxin B failed to inhibit responses, indicating that media contamination was not contributing to biological assays. All three preparations were able to stimulate proliferation of mononuclear cells from naive C3H/HeJ and BALB/c mice. Depletion experiments indicated that the responding cells were B lymphocytes and not T lymphocytes. Purified OspA and OspB stimulated immunoglobulin M production by splenocyte cultures from naive mice, a property also previously attributed to sonicated B. burgdorferi. OspA and OspB also stimulated the production of IL-6 and tumor necrosis factor alpha by bone marrow-derived macrophages from BALB/c and C3H/HeJ mice. Cytokine production was enhanced by the presence of gamma interferon in the cultures, indicating that the magnitude of responses to these lipoproteins may be modulated by cytokines in the microenvironment of infected tissues. Human endothelial cells produced IL-6 when incubated with OspA and OspB, indicating that non-hematopoietic lineage cells can respond to the lipoproteins. Purified OspA and OspB had approximately equal activity, with responses detected in the range of 10 ng of lipoprotein per ml to 1 microgram of lipoprotein per ml. Comparison with published dose responses for lipoproteins purified from Escherichia coli indicates that OspA and OspB purified from B. burgdorferi are much more potent. The high potency of the B. burgdorferi lipoproteins and the ability of the spirochete to invade tissues and persist argue that they could be important in the localized events contributing to the pathology of Lyme disease. PMID- 8359906 TI - Aeromonas salmonicida grown in vivo. AB - The virulent fish pathogen Aeromonas salmonicida was rapidly killed in vivo when restricted inside a diffusion chamber implanted intraperitoneally in rainbow trout. After a period of regrowth, the survivors had acquired resistance to host mediated bacteriolysis, phagocytosis, and oxidative killing, properties which were subsequently lost by growth in vitro. Resistance to bacteriolysis and phagocytosis was associated with a newly acquired capsular layer revealed by acidic polysaccharide staining and electron microscopy. This capsular layer shielded the underlying, regular surface array (S-layer) from immunogold labeling with a primary antibody to the S-layer protein. Resistance to oxidative killing was mediated by a mechanism not associated with the presence of the capsular layer. An attenuated vaccine strain of A. salmonicida grown in vivo failed to express the capsular layer. Consequently, the in vivo-grown cells of this attenuated strain remained as sensitive to bacteriolysis, and as avidly adherent to macrophages, as the in vitro-grown cells. The importance of these new virulence determinants and their relation to the known virulence factors of A. salmonicida are discussed. PMID- 8359907 TI - A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides. AB - During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria. PMID- 8359908 TI - Inhibition of lipopolysaccharide-associated endotoxin activities in vitro and in vivo by the human anti-lipid A monoclonal antibody SdJ5-1.17.15. AB - The present study evaluated the effect of a novel anti-lipid A monoclonal antibody, termed SdJ5, on the in vitro production of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta by endotoxin- or lipopolysaccharide (LPS) challenged human peripheral blood mononuclear cells (hPBMC). In addition, the present study determined whether SdJ5 could neutralize the in vivo toxicity of LPS. SdJ5, at a concentration equal to or greater than 3 micrograms/ml, specifically inhibited TNF-alpha and interleukin-1 beta production by hPBMC stimulated with every type of LPS and lipid A assessed. SdJ5 also showed a significantly greater inhibition of cytokine production than a nonrelevant human immunoglobulin M myeloma control. The SdJ5-mediated inhibition of TNF-alpha production was rapid, as the simultaneous addition of the SdJ5 and LPS still resulted in a marked decrease in hPBMC cytokine synthesis. The ability of SdJ5 to neutralize in vivo toxicity was also determined by using LPS from four different strains of gram-negative bacteria. LPS, when preincubated with SdJ5, resulted in a significant decrease in the 24-h mortality rate compared with that for the control. These studies show that the anti-lipid A monoclonal antibody SdJ5 can modulate LPS-induced cytokine production in vitro and increase the survival rate of rats challenged with lethal doses of LPS. PMID- 8359909 TI - The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine arthritis model. AB - We have studied the role of the accessory gene regulator (agr) of Staphylococcus aureus as a virulence determinant in the pathogenesis of septic arthritis. At least 15 genes coding for potential virulence factors in Staphylococcus aureus are regulated by a putative multicomponent signal transduction system encoded by the agr/hld locus. agr and hld mutants show a decreased synthesis of extracellular toxins and enzymes, such as alpha-, beta-, and delta-hemolysin, leucocidin, lipase, hyaluronate lyase, and proteases, and at the same time an increased synthesis of coagulase and protein A as compared with the wild-type counterpart. We have used a recently described murine model of S. aureus-induced arthritis to study the virulence of S. aureus 8325-4 and two agr/hld mutants derived from it. Sixty percent of the mice injected with the wild-type strain developed arthritis, whereas agrA and hld mutants displayed joint involvement in only 10 and 30%, respectively. In addition, 40% of the mice inoculated with the wild-type strain displayed an erosive arthropathy; such changes were not detectable at all in mice inoculated with the agrA mutant. Serum levels of interleukin-6, a potent B-cell differentiation factor, were significantly higher (P < 0.001) in the mice inoculated with the wild-type strain than in those inoculated with the agrA mutant counterpart. Overall, our results suggest that the agr system of S. aureus is an important virulence determinant in the induction and progression of septic arthritis in mice. PMID- 8359910 TI - Shiga toxin-associated hemolytic uremic syndrome: interleukin-1 beta enhancement of Shiga toxin cytotoxicity toward human vascular endothelial cells in vitro. AB - Development of hemolytic uremic syndrome (HUS) after infection by Shigella dysenteriae 1 or enterohemorrhagic Escherichia coli has been associated with the production of Shiga toxins (verotoxins). The putative target of Shiga toxins in HUS is the renal microvascular endothelium. This report shows that preincubation of human umbilical vein endothelial cells (HUVEC) with interleukin-1 beta (IL-1 beta) enhances the cytotoxic potency of Shiga toxin toward HUVEC. A preincubation of HUVEC with IL-1 beta is required for sensitization of HUVEC to Shiga toxin. Sensitization of HUVEC to Shiga toxin is IL-1 beta dose dependent. Development of the IL-1 beta response is time dependent, beginning within 2 h of IL-1 beta preincubation and increasing over the next 24 h. That these responses were due to IL-1 beta was demonstrated by heat inactivation of IL-1 beta, by neutralization of IL-1 beta by specific antibody, and by the ability of an IL-1 beta receptor antagonist to inhibit the effect of IL-1 beta. Shiga toxin-related inhibition of HUVEC protein synthesis preceded loss of cell viability. IL-1 beta incubation with HUVEC induced the receptor for Shiga toxin, globotriaosylceramide. Lipopolysaccharide included during IL-1 beta preincubation with HUVEC increased sensitivity to Shiga toxin in an additive manner. We conclude that IL-1 beta may induce Shiga toxin sensitivity in endothelial cells and contribute to the development of HUS. PMID- 8359911 TI - Specific adherence of Borrelia burgdorferi extracellular vesicles to human endothelial cells in culture. AB - Borrelia burgdorferi produces extracellular vesicles which contain some of the outer surface proteins of the bacterium (e.g., OspA and OspB). Borrelial vesicles, isolated by differential centrifugation and filtration, were tested for the ability to bind to cultured human umbilical vein endothelial (HUVE) cells in culture. The recently described lipoprotein OspD was expressed on vesicles. Vesicles exhibited differential expression of OspB and OspD in a relationship with passage number and medium serum supplement type, respectively. Qualitative immunoblotting analyses demonstrated dose-dependent, passage number-dependent adsorption of vesicles by HUVE cells. This adsorption was demonstrated to be dependent upon a borrelial component of the vesicle and not due to the presence of minor contamination with intact spirochetes. Quantitative experiments examining inhibition of B. burgdorferi-HUVE association as a function of prior vesicle-HUVE association demonstrated dependence upon (i) a borrelial component(s) in the vesicle, (ii) low passage number, and (iii) vesicle protein concentration. However, vesicle pretreatment of the HUVE cell monolayer was not requisite for this inhibition. Vesicles from highly passaged borrelias were noninhibitory for B. burgdorferi-HUVE cell association, regardless of the serum used to supplement the medium. The use of vesicles as a tool for studying B. burgdorferi pathogenesis and/or physiology is proposed. PMID- 8359912 TI - Comparison of gamma interferon, tumor necrosis factor, and direct cell contact in activation of antimycobacterial defense in murine macrophages. AB - We compared the abilities of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and sensitized murine lymph node lymphocytes to activate syngeneic murine peritoneal macrophages to inhibit the growth of intracellular Mycobacterium bovis BCG in vitro. IFN-gamma could activate antimycobacterial defense only when added to macrophage cultures prior to their infection with BCG. TNF-alpha was without any effect. In contrast, BCG-sensitized lymphocytes could induce antimycobacterial defenses when added after macrophages had been infected with BCG. The cell-mediated effect required direct contact between effector lymphocytes and the targets (BCG-infected macrophages), as revealed in studies in which these cell populations were separated by a semipermeable membrane. Cyclosporin A, which inhibits the production of relevant macrophage-activating lymphokines, did not abrogate the ability of sensitized lymphocytes to activate antimycobacterial effects in infected macrophages. Furthermore, only BCG sensitized lymphocytes, and not Listeria-sensitized lymphocytes, could activate the antimycobacterial effects. These lymphocytes were not cytotoxic to the infected macrophages. The presence of anti-TNF-alpha antibody in cocultures reduced the antimicrobial effects. We propose that the activation of antimycobacterial defense in macrophages can occur by direct physical contact with sensitized lymphocytes. This process may be due to lymphocyte membrane associated TNF-alpha, as we previously demonstrated in our studies of antileishmanial defense. PMID- 8359913 TI - Cellular internalization in the absence of invasin expression is promoted by the Yersinia pseudotuberculosis yadA product. AB - The Yersinia pseudotuberculosis invasin protein is able to promote bacterial penetration into mammalian cells. Insertion mutations that eliminate production of this protein show residual internalization that is dependent on the presence of the Yersinia virulence plasmid. An enrichment procedure was used to isolate molecular clones containing regions of the virulence plasmid that confer this low level uptake on Y. pseudotuberculosis inv mutants. All of the Y. pseudotuberculosis strains isolated from this procedure harbored plasmids containing a region encompassing the yadA gene, which encodes a previously identified adhesin associated with attachment to extracellular matrix proteins. All of the mutations isolated that affected internalization of one of the strains that survived the enrichment disrupted the yadA open reading frame. Furthermore, a strain that contained yadA sequences and no other region of the virulence plasmid was able to promote internalization of a Y. pseudotuberculosis inv mutant. Consistent with these results, an intact virulence plasmid containing an insertion mutation in yadA was as defective as a plasmid-cured strain at promoting uptake of Y. pseudotuberculosis inv mutants. These results indicate that the product of the yadA gene is responsible for the plasmid-dependent entry observed in Y. pseudotuberculosis inv mutants. PMID- 8359914 TI - Purification and partial characterization of a product from Yersinia pseudotuberculosis with the ability to activate human T cells. AB - We tried to purify a substance exhibiting mitogenicity for human peripheral blood lymphocytes from Yersinia pseudotuberculosis isolated from patients with Y. pseudotuberculosis infection manifesting acute and systemic clinical symptoms. The supernatant of a suspension of the bacteria disrupted by sonication was serially chromatographed on DEAE-Sepharose fast-flow, Sephacryl S-100 HR, and TSK gel G2000SW high-pressure liquid chromatography columns. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis revealed that the purified mitogenically active substance migrated as a single band corresponding to a molecular mass of 21 kDa. We designated the purified substance Y. pseudotuberculosis-derived mitogen (YPM). YPM stimulated human peripheral T cells to proliferate and produce interleukin-2 at 0.1 ng/ml or more. YPM-induced T-cell activation required the expression of HLA class II molecules on accessory cells. PMID- 8359915 TI - Immunogenicity of the Plasmodium falciparum serine repeat antigen (p126) expressed by vaccinia virus. AB - cDNA encoding the serine repeat antigen (SERA) (also called p126) of Plasmodium falciparum has been isolated from the FCR3 strain and inserted into a recombinant vaccinia virus designated vP870. Expression analysis of vP870-infected Vero cells by immunoprecipitation has demonstrated several intracellular forms of SERA and a single secreted SERA peptide. Endoglycosidase digestion of these immunoprecipitated SERA peptides indicated that the intracellular SERA peptides contain simple, high-mannose N-linked oligosaccharides and that the secreted SERA peptide contains complex N-linked oligosaccharides. Pulse-chase experiments indicate that the multiple intracellular SERA peptides in infected Vero cells represent a trafficking pathway whereby the smallest SERA peptide is converted into larger peptides by co- and posttranslational modifications, including glycosylation, and eventually secreted from the cell with complex N-linked oligosaccharides. To study the immunogenicity of vaccinia virus-expressed SERA, rabbits were immunized with vP870 and their sera were analyzed for reactivity with authentic, parasite-derived SERA protein. The anti-vP870 rabbit sera reacted with P. falciparum-infected erythrocytes by immunofluorescence analysis, recognized authentic SERA from schizonts by both immunoprecipitation and Western blot (immunoblot) analyses, and recognized proteolytically processed fragments of SERA secreted into the culture medium by Western blot analysis. These results indicate that when expressed by vaccinia virus, SERA is glycosylated and secreted from infected cells and that in immunized rabbits, vaccinia virus-expressed SERA can stimulate a humoral immune response against SERA derived from blood-stage parasites. PMID- 8359916 TI - Expression of the Pasteurella haemolytica leukotoxin is inhibited by a locus that encodes an ATP-binding cassette homolog. AB - Multicopy and single-copy chromosomal fusions between the Pasteurella haemolytica leukotoxin regulatory region and the Escherichia coli beta-galactosidase gene have been constructed. These fusions were used as reporters to identify and isolate regulators of leukotoxin expression from a P. haemolytica cosmid library. A cosmid clone, which inhibited leukotoxin expression from multicopy and single copy protein fusions, was isolated and found to contain the complete leukotoxin gene cluster plus additional upstream sequences. The locus responsible for inhibition of expression from leukotoxin-beta-galactosidase fusions was mapped within these upstream sequences, by transposon mutagenesis with Tn5, and its DNA sequence was determined. The inhibitory activity was found to be associated with a predicted 440-amino-acid reading frame (lapA) that lies within a four-gene arginine transport locus. LapA is predicted to be the nucleotide-binding component of this transport system and shares homology with the Clp family of proteases. PMID- 8359917 TI - Impaired mucosal antibody response to cholera toxin in vitamin A-deficient rats immunized with oral cholera vaccine. AB - To investigate the importance of vitamin A in the ability to respond to oral antigen administration, rats were fed a vitamin A-free diet. The animals were immunized perorally three times with a mixture of cholera toxin (CT) and a commercial cholera vaccine. The total immunoglobulin A (IgA) concentration as well as the specific IgA anti-CT antibody levels in serum and bile was significantly lower in the vitamin A-deficient animals than in the paired fed controls (animals that were fed a normal commercial diet in an amount equal to the amount the deficient animals consumed), while the levels of total and specific anti-CT IgG were not affected to the same extent by the vitamin A deficiency. The number of IgA anti-CT antibody-producing cells in the mesenteric lymph nodes after immunization was also significantly lower in the vitamin A deficient rats than in the control rats. Supplementation of the diet with retinyl palmitate restored the ability to mount an IgA antibody response to the antigen, since the level of specific IgA anti-CT antibodies in relation to the total IgA concentration was as high in the vitamin A-supplemented group as in the paired fed control group. Restricted diet intake by itself did not affect the ability to respond adequately to the antigen since there was no difference in IgA anti-CT antibody level between paired fed rats and those being fed ad libitum. Assessment of transforming growth factor beta in cell cultures revealed no difference between vitamin A-deficient and paired fed animals. In summary, vitamin A deficiency resulted in a decreased number of IgA-producing cells, decreased IgA production, and a reduced ability to respond with IgA antibodies to the oral cholera vaccine. PMID- 8359918 TI - Molecular genetic analysis of beta-toxin of Clostridium perfringens reveals sequence homology with alpha-toxin, gamma-toxin, and leukocidin of Staphylococcus aureus. AB - Oligonucleotide probes designed on the basis of the N-terminal sequence of Clostridium perfringens beta-toxin were used to isolate the encoding gene (cpb). The nucleotide sequence of cpb was determined, and on the basis of DNA hybridization experiments it was shown that the gene is found only in type B and C strains of C. perfringens. The deduced amino acid sequence of the beta-toxin revealed homology with the alpha-toxin, gamma-toxin, and leukocidin of Staphylococcus aureus. The beta-toxin purified from C. perfringens appeared to exist in monomeric and multimeric forms. Recombinant beta-toxin, produced in Escherichia coli, appeared to be mainly in the multimeric form. PMID- 8359919 TI - Tumor necrosis factor alpha (TNF-alpha) production in mice immunized with Escherichia coli: correlation with mortality after lethal challenge and production of a native inhibitor of TNF-alpha activity. AB - The kinetics of tumor necrosis factor alpha (TNF-alpha) production, the correlation between cytokine levels and mortality rates after lethal challenge, and the production of a native inhibitor of TNF-alpha activity was investigated in mice immunized with formalin-killed Escherichia coli. Groups of mice were injected for 8 weeks with either untreated bacteria or bacteria treated with 0.5 MIC of aztreonam and subsequently challenged with 100 50% lethal doses of viable E. coli. Mice receiving saline only (controls) died within 24 h. The mortality of mice immunized with aztreonam-treated E. coli was significantly lower than that of mice immunized with untreated E. coli. There were no measurable levels of TNF alpha in sera obtained from control mice during the entire period of immunization. TNF-alpha levels ranging from 90 to 306 U/ml were measured 90 min after each vaccination in sera obtained from mice immunized with untreated E. coli. Sera from mice immunized with antibiotic-treated E. coli showed lower TNF alpha levels, ranging from 40 to 128 U/ml. TNF-alpha levels measured 90 min after lethal challenge correlated with the mortality rate observed in each group (r = 0.95). The cytotoxic activity of recombinant murine TNF-alpha was inhibited by the sera from immunized mice but not by the sera from controls. The inhibition was drastically reduced by preincubation of the sera with staphylococcal protein A. In immunoblot experiments, class G immunoglobulins reacting with recombinant murine TNF-alpha were observed in the sera of immunized mice. These data confirm the correlation existing between TNF-alpha levels and mortality and suggest that native inhibitors may play a role in the regulation of the biological function of the cytokine. PMID- 8359920 TI - Adoptive transfer of immunity to oral challenge with virulent salmonellae in innately susceptible BALB/c mice requires both immune serum and T cells. AB - The mechanisms of immunity to salmonellae conferred by immunization with live vaccines were studied by adoptive transfer using the mouse-virulent strain Salmonella typhimurium C5 and innately susceptible BALB/c (ltys) mice. This organism cannot establish a sublethal infection in naive BALB/c mice. Animals immunized 2 to 3 months earlier with the S. typhimurium SL3261 aroA live vaccine were used as donors of serum, spleen cells, and mesenteric lymph node cells for naive recipients which were challenged orally with the virulent C5 strain. Simultaneous transfer of both immune serum and immune cells was necessary for protection. Simultaneously depleting the donors of CD4+ and CD8+ T cells by administration of antisera in vivo prior to cell harvesting showed that T cells were necessary for protection. The results demonstrate that both antibody and T cells are required for recall of immunity to oral challenge with virulent salmonellae in innately susceptible mice and suggest that the ability to elicit opsonizing antibody in addition to cell-mediated immunity is important for optimal protection induced by salmonella vaccines. PMID- 8359921 TI - Fibroblast-stimulating factor 1, a novel lymphokine produced in schistosomal egg granulomas, stimulates liver fat-storing cells in vitro. AB - We report that the novel lymphokine fibroblast-stimulating factor 1, produced within hepatic schistosomal egg granulomas, stimulates liver fat-storing cells (FSC) in vitro to proliferate and express fibronectin genes. Because FSC are critical in hepatic fibrogenesis generally, we propose that in vivo stimulation of FSC by fibroblast-stimulating factor 1 may be an important step in schistosomal liver fibrosis. PMID- 8359922 TI - Clostridium difficile toxin A elicits Ca(2+)-independent cytotoxic effects in cultured normal rat intestinal crypt cells. AB - In rat intestinal crypt cells, Clostridium difficile toxin A induces (i) early cytoskeletal alterations involving the whole population and (ii) late effects in 30 to 40% of the cells, consisting mainly of surface blebbing and nuclear fragmentation. All these effects were Ca2+ independent and were not abolished by protein synthesis inhibitors. PMID- 8359923 TI - Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels. AB - Groups of 122 Peruvian adults of low socioeconomic level (SEL) and 125 of high SEL received a randomly allocated 5 x 10(9)- or 5 x 10(8)-CFU dose of CVD 103-HgR live oral cholera vaccine or a placebo. The vaccine was well tolerated. Vibriocidal seroconversions occurred in 78% of high-SEL and 72% of low-SEL subjects who ingested the high dose and in 78 and 49%, respectively, of those who received the low dose. PMID- 8359924 TI - Similar proportions of immunoglobulin A1 (IgA1) protease-producing streptococci in initial dental plaque of selectively IgA-deficient and normal individuals. AB - By comparing the initial colonization of cleaned teeth in immunoglobulin A (IgA) deficient, IgM-compensating individuals with that in normal individuals, no significant difference in the proportion of IgA1 protease-producing streptococci was found. Thus, as one of several bacterial means of immune evasion, the ability to cleave secretory IgA1 does not appear essential to the successful adherence of oral streptococci. PMID- 8359925 TI - Actin accumulation at sites of attachment of indigenous apathogenic segmented filamentous bacteria to mouse ileal epithelial cells. AB - Selective attachment of indigenous, apathogenic, segmented filamentous bacteria to follicle-associated epithelia of terminal ileal Peyer's patches involves both the specialized M cells and normal enterocytes. A striking, highly localized cytoplasmic accumulation of polymerized actin, which resembles that associated with adherence of enteropathogenic Escherichia coli to cultured epithelial cells, occurs at attachment sites of segmented filamentous bacteria. The epithelial response to the attachment of microorganisms may thus involve mechanisms which are the same for diverse microorganisms. PMID- 8359926 TI - Immunological properties of ribosomal proteins from Mycobacterium bovis BCG. AB - Two proteins with molecular mass 65 kDa, a heat shock protein, and an S1-like protein were found in a 30S ribosomal subunit from Mycobacterium bovis BCG. The 17-kDa protein in the 30S subunit was homologous to alpha-crystallin heat shock protein, and the 16-kDa protein in the 50S subunit was homologous to the L7/L12 protein. The latter provoked a strong delayed-type hypersensitivity reaction in the sensitized guinea pigs. The GroES-like protein (12 kDa) loosely associated with ribosomes. PMID- 8359927 TI - Interleukin-7 enhances antimicrobial activity against Leishmania major in murine macrophages. AB - Recently, it has been shown that interleukin-7 (IL-7) is able to induce secretion of cytokines and tumoricidal activity by human monocytes. This study shows that treatment of murine macrophages infected with Leishmania major with IL-7 without any other stimulus reduced the percentage of infected cells, as well as the parasite burden per cell, in a dose-dependent manner to a limited degree (45% reduction of the number of amastigotes per 100 macrophages). Simultaneous treatment of macrophages with gamma interferon and IL-7 led to nearly complete (> 99%) elimination of amastigotes. Addition of anti-tumor necrosis factor alpha or N omega-monomethyl-L-arginine acetate reversed the leishmanicidal effects of IL 7, and production of nitric oxide was induced in the presence of IL-7. PMID- 8359928 TI - Staphylococcus-mediated T-cell activation and spontaneous natural killer cell activity in the absence of major histocompatibility complex class II molecules. AB - We used major histocompatibility complex class II antigen-deficient transgenic mice to show that in vitro natural killer cell cytotoxicity and T-cell activation by staphylococcal exotoxins (superantigens) are not dependent upon the presence of major histocompatibility complex class II molecules. T cells can be activated by exotoxins in the presence of exogenously added interleukin 1 or 2 or in the presence of specific antibody without exogenously added cytokines. PMID- 8359929 TI - Molecular cloning and sequence of the gene for outer membrane protein P5 of Haemophilus influenzae. AB - The gene for outer membrane protein P5 of Haemophilus influenzae was identified by immunological screening of a genomic lambda EMBL3 library of the serotype b strain 1613. The gene was subcloned, and plasmid clones expressing P5 were identified by immunologic screening. The gene for outer membrane protein P5 was sequenced. The mature protein has a molecular weight of 35,628. The protein is 50% identical and 65% similar to the OmpA protein of Escherichia coli. PMID- 8359930 TI - Vasectomy and health revisited. PMID- 8359931 TI - Effect of chronic alcoholism on semen--studies on lipid profiles. AB - The effect of chronic alcoholism on various seminal parameters (sperm concentration, rate of forward motility, percentage of abnormal spermatozoa, lipid profiles of seminal plasma and spermatozoa) was studied together with the serum levels of testosterone and oestradiol. In chronic alcoholics there was a marked reduction in sperm concentration and in the rate of their forward motility, and increase in the number of spermatozoa with morphological abnormalities when compared to age-matched normal fertile subjects. Serum levels of testosterone were decreased while oestradiol levels were increased in chronic alcoholic men. Studies of lipid profiles showed a marked decrease in the total phospholipid concentration in spermatozoa, primarily in sphingomyelin, phosphatidyl choline and ethanolamine fractions. The cholesterol:phospholipid ratio in spermatozoa was increased in alcoholics. In the seminal plasma of chronic alcoholics, there was a decrease in total lipid, in glyceride glycerol and in free and esterified cholesterol. Of the phospholipid classes, sphingomyelin and phosphatidyl ethanolamine showed a significant reduction. In general, the present study provides evidence for the adverse effects of chronic alcoholism on serum hormones, sperm count, morphology, motility and seminal lipid profiles. These may be responsible for the fertility disorders common in chronic alcoholics. PMID- 8359932 TI - Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa. AB - Reactive oxygen species (ROS) can be detected in the semen of 40% of infertile men, whereas none is detected in semen from normal men. The ROS detected in semen are a reflection of the imbalance between ROS production and degradation. The aim of the present study was to determine whether a lowered scavenging capacity or an increased production of ROS was responsible for the ROS detected in semen samples from infertile men. Two activities were investigated: (1) catalase-like activity, which is responsible for the degradation of H2O2 and (2) superoxide dismutase like (SOD-like) activity which is responsible for the degradation of .O2-. Catalase-like and SOD-like activities were found in whole seminal plasma, in dialyzed seminal plasma (> 12 kD), in an ultrafiltrate of seminal plasma (< 5 kD) and in spermatozoa. There was no significant difference in the SOD-like activities measured in spermatozoa, or in seminal plasma (whole or fractionated) from samples that did or did not produce ROS. SOD-like activity originated mostly from the high molecular weight components of seminal plasma. However, the catalase-like activity of whole seminal plasma and of spermatozoa was significantly greater (P = 0.01) in those samples that produced ROS as compared to those that did not. The catalase-like activity in dialyzed seminal plasma, and an ultrafiltrate of seminal plasma from semen samples that did or did not produce ROS were not statistically different. The catalase-like activity of the seminal plasma originated equally from high and low molecular weight components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359933 TI - Seminal leucocyte subpopulations and sperm function in fertile and infertile Chinese men. AB - The level of seminal leucocytes and the prevalence of leucocytospermia was determined in a group of fertile and infertile southern Chinese men in Hong Kong. Sixteen normal fertile semen donors and 49 men with male factor infertility were studied prospectively. None had antisperm antibodies and past or present evidence of genital tract infection. Seminal leucocytes and their subsets were analysed using monoclonal antibodies and an immunocytochemical alkaline phosphatase-anti alkaline phosphatase conjugate technique. Seminal leucocytes were detectable in 94% and 86% of the fertile and infertile men respectively, with the predominant subset being granulocytes. Leucocytospermia (> 1 x 10(6) leucocytes/ml) was found in only one of the 49 (2%) infertile men without clinical evidence of genito urinary infection. Inverse correlations were observed between (1) the percentage of spermatozoa with normal morphology and the number of T-helper/inducer cells, (2) the linearity of sperm movement and the number of T-lymphocytes. In conclusion, the level of seminal leucocytes and the prevalence of leucocytospermia is low in infertile Chinese subjects. The effect of seminal leucocytes on sperm function in these subjects needs further evaluation. PMID- 8359934 TI - Diurnal variations in scrotal temperature of normal men and patients with varicocele before and after treatment. AB - Scrotal temperature was monitored using a portable data recorder for periods of 24 h in six normal volunteers and 48 infertile patients with unilateral varicocele while subjects pursued their regular daily activities. Temperatures during sleep (TS) were generally higher than daytime values (TD), probably as a consequence of thermal insulation in bed. These diurnal variations were found to be less pronounced in the infertile patients than in volunteers (TS - TD = 0.29 degrees C +/- 0.06 degrees C vs 0.88 degrees C +/- 0.12 degrees C; P < 0.01). Moreover, scrotal temperatures at night of patients and volunteers were indistinguishable statistically, but were different during daytime hours. After successful ligation or embolization of the spermatic-vein in 16 patients, no change in scrotal temperature was observed. Although sperm counts were higher after treatment, this difference was not significant (67.4 +/- 17.2 x 10(6) vs 105.8 +/- 25.5 x 10(6); P > 0.05). The data support the view that varicocele related damage to the testis results from a lack of adequate cooling, and that treatment does not normalize the temperature pattern. PMID- 8359935 TI - Plasminogen activator activity and fertilizing ability of human spermatozoa. AB - Mature spermatozoa contain a number of proteases that are supposed to contribute to their fertilizing ability. The present study was directed at plasminogen activator (PA), a protease that belongs to the group of serine proteases and converts the zymogen plasminogen to the active broad-spectrum protease plasmin. To investigate the possible role of PA in the fertilization process, we have measured sperm-bound PA activity in 63 patients included in an in-vitro fertilization (IVF) programme and assessed their relationship to standard semen parameters and the rate of fertilization. PA activity was correlated significantly with the sperm count, as well as with sperm motility and morphology. Using logistic regression analysis, specific PA (pmol pNA 10(-6) cells min-2) was found to significantly influence the probability of fertilization. Other significantly predictive factors were motility and the percentage of spermatozoa with normal morphology. The sperm concentration (10(6) cells ml-1) did not significantly affect the outcome of IVF. We suggest that sperm-bound PA is involved in the fertilization process and may represent a potential indicator of sperm fertilizing capacity. PMID- 8359936 TI - The detection of antisperm antibodies in serum: a comparison of the tray agglutination test, indirect immunobead test and indirect SpermCheck assay. AB - Testing for antisperm antibodies (ASAs) is an important part of the work-up of the sub-fertile couple, yet there is little consensus regarding the most appropriate methods. The SpermCheck assay (GSC; Bio-Rad Laboratories Inc., Diagnostics Division, Hercules, CA, U.S.A.) is supplied with wash buffer, controls and bead reagent which detects all three major classes of ASAs (IgA, IgG and IgM) in a single test. This study compared results on a bank of samples using the tray agglutination test (TAT), immunobead test (IBT), GSC and a modified SpermCheck assay to detect a single isotype in each test (SISC). The IBT and SISC showed excellent correlation, with 127/141 (90.1%) tests agreeing. There was an apparent lack of sensitivity to IgM with GSC as 8/15 (53.3%) samples testing positive with IBT and 7/15 (46.7%) testing positive with SISC were negative with GSC. Of the 24 IBT-negatives, seven (29.2%) were positive for TAT, indicating a high incidence of non-immunological agglutination, though this decreased as the TAT titre increased. The proportion of samples testing positive for IBT increased with TAT titre: 3/20 (15.0%) for TAT-negative samples, 6/10 (60.0%) for low titres and 21/24 (87.5%) for high titres. This was also observed when comparing the GSC with TAT. The TAT therefore appears useful as a first-line screen, whilst the inability of the GSC to adequately detect IgM limits its use as an indirect test. Both the IBT and SISC can be used to further investigate the type and class of ASA present. PMID- 8359937 TI - Immunohistochemical localization of calmodulin in the testes of patients with idiopathic male infertility. AB - The localization of calmodulin in testes of patients with idiopathic male infertility was studied using the indirect immunoperoxidase method. Specimens were obtained by testicular biopsy from 55 patients. They were divided into 26 cases of hypospermatogenesis, 11 cases of maturation arrest (8 of primary spermatocyte arrest and 3 of spermatid arrest) and 18 cases of Sertoli cell-only syndrome. Regardless of the type of testicular pathology, the types of immunoreactive cell and the intensities of staining were the same as those in the normal testis. That is, staining for calmodulin was first found to be positive in early pachytene primary spermatocytes. It became intense in late pachytene primary spermatocytes and round spermatids. By contrast, elongated spermatids and spermatozoa were not stained. Sertoli cells were stained slightly or not at all. A calmodulin-staining index (CaM-S index) was defined as the proportion of primary spermatocytes that were stained intensely for calmodulin relative to the total number of primary spermatocytes. The indices for the testes of men with complete spermatocyte maturation arrest were significantly lower than those for the testes of normal controls and of men with hypospermatogenesis. Degenerating late pachytene spermatocytes observed in the testes of men with spermatocyte arrest showed low calmodulin-specific immunoreactivity. Such a decrease in numbers of normal late pachytene spermatocytes might be responsible for the low CaM-S index in cases of complete spermatocyte arrest. PMID- 8359938 TI - Is testosterone essential for maintenance of normal morphology in immature rat Leydig cells? AB - Selective deprivation of gonadotrophins in prepubertal rats by administration of a GnRH antagonist (Ac-D2Nal1, D4ClPhe2, DTrp3, DArg6, DA1a10-GnRH; GnRH code: 103 289-10, National Institutes of Health, USA) for 3 weeks, initiated at 20-22 days of age, induced morphological changes in the Leydig cells, including thickening and indentation of the nuclear margin, pyknosis and elongation of the nuclei. Mean nuclear diameter was reduced to 22% of that in the controls. Under the electron microscope the cells exhibited reduced volume of the nucleus and cytoplasm and the plasma membrane was irregular. This abnormal appearance of the Leydig cells improved marginally in 20-30% of the Leydig cells and their mean nuclear diameter increased to 39% of the control level after FSH supplementation (20 micrograms ovine FSH/day). Normal morphological integrity of the Leydig cells consisting of round or oval nuclei, a smooth nuclear and cellular margin and the original mean nuclear diameter was restored completely when testosterone (30 micrograms/day) was administered to GnRH antagonist-treated rats, with or without simultaneous administration of FSH; in these rats testosterone levels in blood were also restored to normal. These findings indicate that testosterone may be important for the maintenance of normal Leydig cell morphology in the rat. PMID- 8359939 TI - Arachidonic acid metabolites as intratesticular factors controlling androgen production. AB - The effect of inhibitors and products of arachidonic acid metabolism on rat testicular steroidogenesis has been investigated. In the presence of indomethacin (inhibitor of cyclooxygenase) and nordihydroguaiaretic acid (NDGA) (inhibitor of lipoxygenase), the activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were both inhibited. The LH-stimulated increase in secretion of testosterone and progesterone was also inhibited by indomethacin and NDGA. On the other hand, vitamin E (antioxidant and inhibitor of lipoxygenase), stimulated the activity of both 3 beta-HSD and 17 beta-HSD and enhanced LH-stimulated androgen production. The metabolites of lipoxygenase (15-HPETE, 15-HETE, 5-HPETE and 5-HETE) and cyclooxygenase (PGF2 alpha) pathways stimulated 3 beta-HSD and 17 beta-HSD activity and enhanced the secretion of progesterone and testosterone. It is concluded that arachidonic acid metabolites are intratesticular factors which can regulate LH-stimulated testicular steroidogenesis. PMID- 8359940 TI - Alterations in testicular function after endotoxin injection in the boar. AB - Twelve mature boars were injected intravenously with endotoxin from Salmonella typhimurium. Blood plasma was analysed for 15-ketodihydro-PGF2 alpha, LH and testosterone. The boars were castrated at various times after endotoxin administration and the testes examined by light and electron microscopy. The levels of 15-ketodihydro-PGF2 alpha and LH rose immediately after endotoxin injection followed by an increase in testosterone levels, and in five boars a second increase in LH levels was observed. Morphological examination of the testes revealed infiltration of polymorphonuclear neutrophils (PMN) into the testicular interstitium. The Leydig and myoid cells showed morphological changes. Alterations were also present in the seminiferous epithelium among Sertoli cells, spermatocytes and spermatids. The results indicate that endotoxins can exert a negative effect on testicular function in the boar. Except for the initial increase in LH levels, which is not clearly understood, the hormonal changes are thought to be mediated by alterations in Leydig cell function. The alterations further support previous findings in the boar, and indicate that there is short term, moderate damage to the seminiferous epithelium following endotoxin injection. PMID- 8359941 TI - Naturalistic observation of adolescent tobacco use. AB - A naturalistic observation study of adolescent tobacco use was conducted to corroborate previous studies which used self-report questionnaire or structured interview methods to study this problem behavior. Several findings converged with previous accounts of adolescent tobacco use. For example, most use occurred in small groups. However, other findings diverged somewhat from previous research in that an unexpectedly low number of offers of tobacco was observed, nonusers were present in smoking groups, and solitary smoking was common. These data suggest that direct, normative social pressure to use tobacco may not be as frequent as more subtle informational social influence, at least in high school adolescent tobacco use groups. PMID- 8359942 TI - The link between identity and crime for the heroin addict in methadone treatment. AB - In this paper we examine the relationship between identity and involvement in crime for the heroin addict enrolled in methadone treatment. We hypothesize that crime during treatment is related to the maintenance of an identity appropriate to the role of the active street hustler. Data derive from interviews with addicts in methadone treatment in the New York City area. The major finding is that addicts in methadone treatment who had street-oriented identities were more likely than those with model patient-based identities to be involved in crime, particularly property crime. The limitations and implications of this research are discussed. PMID- 8359943 TI - Alcoholics initial expectancies of and attitudes toward treatment. AB - In one study, 100 poor inner-city alcoholics were asked about their expectancies of the counselor's behavior in an initial interview. The majority expected a medically oriented, supportive, active interviewer who asked them about emotional issues. Eighty percent reported a disconfirmation of at least one expectancy postinterview. In a second study, patient's receptivity to treatment was assessed. That sample was found to accept the need for treatment and to have confidence in the counseling process as well as to be moderately tolerant of the stigma of being alcoholic and interpersonally open. Neither the degree of expectancy disconfirmation or receptivity to treatment predicted patient's subsequent clinic attendance in this patient sample. PMID- 8359944 TI - Potential use of mass media to reach urban intravenous drug users with AIDS prevention messages. AB - To access the potential of using the mass media to reach urban intravenous drug users (IVDUs) with AIDS prevention messages, we: 1) questioned 353 participants in a Baltimore IVDU cohort study on their media use and sources of AIDS information, 2) analyzed data on Baltimore AIDS public service announcement (PSA) airings during a 3-month period, and 3) discussed with media executives their willingness to air a variety of potential AIDS messages. Forty-seven percent of all respondents reported that they learned the most about AIDS from television. Participants watched television a median of 28 hours/week; 52% of IVDUs listened to ratio > or = 12 hours/week. Eight hundred eleven AIDS television PSAs were aired; 37% of PSAs were placed on news programs; 53% of respondents watched news programs. Acceptability of hypothetical prevention messages (e.g., on sexual abstinence, condom use, or safer drug use practices) varied with media reach (national vs local) and type (television vs radio). We conclude that media could reach IVDUs with AIDS prevention messages. Television could be used to direct IVDUs to local prevention programs and provide safe/safer sex messages. Explicit and detailed AIDS prevention messages would be acceptable to some local radio stations. PMID- 8359945 TI - The influence of parent, sibling, and peer modeling and attitudes on adolescent use of alcohol. AB - This 1-year prospective study of 173 families with two or more children examines the influence of parent, sibling, and peer modeling (i.e., use) and attitudes on adolescent use of alcohol. Independent questionnaire data were obtained from the adolescent, father, mother, and sibling(s). Structural equation modeling methods were employed to examine these relationships. Parent attitude toward youth alcohol use and parent modeling of alcohol use were strongly related to change in adolescent alcohol use, suggesting that parents can influence the future use of alcohol by their children. Peer and sibling modeling and peer attitudes also influenced adolescent alcohol use. PMID- 8359946 TI - Reasons for drinking alcohol: their relationship to psychosocial variables and alcohol consumption. AB - The present investigation was designed to gain a better understanding of the psychosocial factors that predict reasons for drinking alcohol and how these drinking motives differentially relate to alcohol consumption. Four distinct reasons for drinking alcohol scales were established through factor analysis: drink to cope, drink to be sociable, drink to enhance social confidence, and drink for enjoyment. Multiple regression analyses showed that 1) each reason for drinking was predicted by a somewhat different set of demographic and psychosocial variables, and 2) the reasons for drinking, in turn, differentially predicted multiple indicators of quantity and frequency of alcohol consumption. Theoretical implications of the study results and suggestions for future research are discussed. PMID- 8359947 TI - Problem severity and symptomatology among substance misusers: differences between African-Americans and Caucasians. AB - Using data collected on 348 patients presenting to a hospital-based substance misuse treatment program, the present study compares psychiatric symptomatology and severity of substance misuse among African-American and Caucasian alcohol and drug misusers. African-Americans had a higher overall severity of substance misuse and reported using more substances than Caucasians. African-Americans also had higher levels of somatization, interpersonal problems, depression, hostility, obsessive/compulsive behavior, phobia, paranoia, and psychoticism than Caucasians. African-Americans exhibited higher levels of psychosocial stress and lower levels of global functioning than did Caucasians. The implications of the findings are discussed. PMID- 8359948 TI - Attitudes of registered nurses toward alcoholic patients in a general hospital population. AB - The Marcus Alcoholism Questionnaire was administered to 66 registered nurses at a community hospital to ascertain their attitudes regarding alcoholic patients in a general hospital population. This was done to provide documentation on what nurses attitudes actually are as opposed to making an assumption about what they should be because of the high visibility of the problem of alcoholism. The author reports the results of the study and then contrasts them with information about registered nurses attitudes toward alcoholic patients at a university hospital. The article concludes with insight into contributing factors for the differences. PMID- 8359949 TI - Health surveillance in Europe: lessons from EUROCAT and Chernobyl. PMID- 8359950 TI - Completeness of cancer registration in Limburg, The Netherlands. AB - The completeness of cancer registration in the IKL (Integraal Kankercentrum Limburg) cancer registry, Limburg, the Netherlands, was evaluated for the years 1988-1990 by means of the independent case ascertainment method. This study was performed in co-operation with the Registration Network of Family Practices (RNFP) of the University of Limburg. The RNFP is a centralized database used by general practitioners (GP), containing their patients' background variables and diagnoses. The contents of the two databases were compared using computerized record linkage. If the information from both databases differed, this was verified using the source forms of the cancer registry and the GP involved. By combining the information from both registries in this way it was determined which malignancies should have been registered by the cancer registry. The IKL cancer registry had recorded 307 of the 319 eligible malignancies (96.2%). Five of the 12 missed registrations could be attributed to systematic shortcomings in the notification procedures. The estimated completeness for all malignancies of the IKL cancer registry is comparable with the results from cancer registries outside the Netherlands which have been established for longer. PMID- 8359951 TI - Mortality patterns and trends for lung cancer and other tobacco-related cancers in the Americas, 1955-1989. AB - Mortality from cancers of the oral cavity and pharynx, oesphagus, larynx and lung between 1955 and 1989 has been analysed for USA, Canada and 14 countries in Latin America. Among males, Uruguay, Cuba, Argentina and Puerto Rico have the highest rates for all sites, and Peru, Ecuador, Dominican Republic, Mexico and Colombia have the lowest rates. Among females, Cuba, Colombia and Puerto Rico rank high for all sites, and Mexico, Paraguay, Ecuador and Peru rank low. For both sexes, lung cancer mortality rates from the US and Canada are high, whereas rates from other sites are intermediate. An increasing trend in lung cancer mortality over time is shown in all countries except Cuba (no changes), Argentina, Paraguay and Peru (decreasing trend). In Latin America, the tobacco-related lung cancer epidemic is in its early phase among males, and very early phase among females. PMID- 8359952 TI - Marital stability and cancer of the uterine cervix: changing patterns in post-war Britain. AB - This study investigates the extent to which the distinctive cross-sectional marital status picture of risk for cancer of the uterine cervix (single, married, widowed, divorced in ascending order of risk) has persisted in post-war Britain. Incidence and mortality due to invasive cervical cancer amongst single women now exceeds that of the married, and for both has become much closer to that of the widowed and divorced. A dramatic increase in carcinoma in situ in Scotland, seen particularly in the single since 1982, must partly reflect changes in screening and diagnostic classification, but is also consistent with the later occurrence of the sexual revolution in Scotland. Overall in Britain, the distribution of screening and hysterectomy cannot account for the present day pattern of the disease. Available data on patterns of smoking and oral contraceptive use are broadly consistent with a role for them in determining the current disease pattern associated with marital status but their possible involvement cannot be disentangled from the more likely effect of changing levels of sexual activity increasing the risk of sexually transmitted disease. As marital status becomes a less important social indicator of sexual behaviour, it has also become a much less reliable marker of cervical cancer risk. PMID- 8359953 TI - Do chart reviews and interviews provide the same information about breast and cervical cancer screening? AB - The National Cancer Institute of the United States has set a goal for the year 2000 that 80-90% of eligible women should have a Pap smear every 3 years and that 80% of women aged 50-70 should receive an annual breast examination and mammogram. Very few studies have examined how we might best measure our progress towards this goal. Specifically, should we employ interview data or data derived from medical records? To respond to this question, data were gathered at two different public health clinics in poor areas of Chicago using both techniques. The interviews estimated significantly higher proportions of women receiving Pap smears, breast examinations, and mammograms in the previous 12-month interval than were estimated from randomly selected medical records. A review of the literature suggests the same pattern exists when other studies using these two data gathering processes are compared. We are thus left with a serious problem, one that must be resolved before we will be able to fully assess our progress in increasing breast and cervical cancer screening. PMID- 8359954 TI - Coffee, tobacco and alcohol as risk factors for cancer and adenoma of the large intestine. AB - Our aim was to estimate the association between smoking history, alcohol and tobacco smoking and tumours of the large intestine. Associations were studied at an early stage of colorectal cancer in order to avoid bias in the information. In order to estimate the link between adenoma and cancer the exposures were analysed separately for cancer and adenoma patients. The study was conducted as a case control study within a randomized trial for colorectal cancer among males and females aged 45-74 years. Cases initially included all individuals with a positive Haemoccult-II test in three screens and an age- and sex-matched reference group was selected from the test negatives. Subsequent colonoscopy defined the final case group, which consisted of 49 colorectal cancer patients, 171 with adenoma and 177 test positives with no diagnosis or with non-adenomatous polyps or haemorrhoids. Controls were 362 age- and sex-matched test negatives. Data were collected by blind telephone interviewing before the first clinical examinations of test positives. Smoking history, coffee or alcohol intake were not statistically significantly associated with colorectal cancer. For adenomas, the odds ratios (OR) were between 2.0 and 2.7 in all smoking categories. For smokers with > 40 years duration OR = 2.7 (95% confidence interval (Cl): 1.6 4.7). Coffee consumption showed a clear protective effect. Consumers of 4-7 cups per day had an OR of 0.5 (95% Cl: 0.3-0.8) and heavy consumers of > or = 8 cups had an OR of 0.3 (95% Cl: 0.1-0.6). Neither tea nor alcohol consumption was related to adenoma risks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359955 TI - Occupational risks of bladder cancer in France: a multicentre case-control study. AB - The relationships between occupational risk factors in France and bladder cancer were assessed from a hospital-based case-control study conducted between 1984 and 1987 in five regions representing various industries, including mining, textile manufacture, metallurgy and the production of rubber and chemicals. The study concerned 765 cases (658 men and 107 women) and the same number of controls. Odds ratios (OR) adjusted for matching variables (age, place of residence and hospital), and tobacco smoking were estimated by unconditional logistic regression. A significantly increased risk of bladder cancer was observed among men employed in coal mining (OR = 2.42; 95% confidence interval (Cl) : 1.25-4.67) and the chemicals industry (OR = 2.36; 95% Cl : 1.23-4.53). Aircraft and ship's officers (OR = 11.8; 95% Cl : 1.46-95.7), managers (OR = 1.64; 95% Cl : 1.11 2.43) and street vendors (OR = 3.60; 95% Cl : 1.15-11.3) also had an increased risk. Among women, employment in the clothing industry was associated with a high OR (= 3.21; 95% Cl : 1.34-7.71). Assessment of individual exposures by a panel of industrial hygiene experts showed that significantly more cases than controls had been exposed to the following substances: chlorinated solvents (OR = 1.86; 95% Cl : 1.19-2.90), industrial oils and greases (OR = 1.44; 95% Cl : 1.10-1.89), welding fumes (OR = 1.40; 95% Cl : 0.98-2.01), coal dust (OR = 1.71; 95% Cl : 1.02-2.89) and metallic oxide dust (OR = 2.99; 95% Cl : 1.12-8.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359956 TI - Tumours of the brain and presence of antibodies to Toxoplasma gondii. AB - The possible association between prior infection with the protozoan Toxoplasma gondii and development of brain tumours was investigated as part of two Australian population-based case-control studies of adult brain tumours. One study, based in Adelaide, South Australia, collected blood from 73 subjects with glioma, 53 subjects with meningioma and 348 controls. The other study, based in Melbourne, Victoria, collected blood from 44 subjects with glioma and 67 controls. All tumours had been verified histologically. IgG antibodies to T. gondii were measured using Enzyme Linked Immunosorbent Assay (ELISA) techniques. In both the centre-specific and combined analyses, there was no difference between subjects with glioma and controls in the prevalence of antibody test positivity (35% test-positive in glioma versus 33% in controls, age-, sex- and centre-adjusted odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.64-1.56). In the Adelaide study, there was a statistically significant increased risk of meningioma associated with antibody test-positivity (47% test-positive in meningioma versus 31% in controls, P = 0.02, adjusted OR = 2.09, 95% CI: 1.14 3.83). Our results do not support the hypothesis that antibody positivity to T. gondii is a risk factor for glioma, but suggest that it might be associated with meningioma. PMID- 8359957 TI - The association of education with coronary heart disease mortality in the USSR Lipid Research Clinics Study. AB - There is a strong inverse association between educational attainment and coronary heart disease (CHD) mortality in men in the USSR Lipid Research Clinics (LRC) Study. Less educated men were characterized by higher mean blood pressure, high density lipoprotein cholesterol (HDL-C), cigarettes smoked and by lower mean low density lipoprotein cholesterol (LDL-C) and body mass index (BMI). With respect to nutritional variables, less educated men were characterized by higher mean energy per kg body weight and alcohol intake and by lower mean intake of fat, saturated, mono- and polyunsaturated fatty acids, cholesterol, sucrose, and other sugars. The Keys score closely predicted the differences in plasma cholesterol among the educational groups in the randomly selected sample. In men without CHD at entry, the age and clinic-adjusted relative risk for CHD mortality was 2.4 for the least educated compared with the most educated group; on adjusting for systolic blood pressure, HDL-C, LDL-C, BMI, alcohol intake and number of cigarettes, the relative risk was reduced to 1.9. These data indicate that only 22% of the twofold excess of CHD mortality associated with low education was statistically attributable to the major risk factors. The failure to explain more of the education-CHD mortality gradient in the USSR LRC cohort was similar to observations from cohort studies in Great Britain and the US. Other correlates of low education must be explored to explain the association. PMID- 8359958 TI - Community-based intervention: the Coronary Risk Factor Study (CORIS). AB - The Coronary Risk Factor Study (CORIS) examined the feasibility and effectiveness of a multifactorial community intervention programme to reduce coronary heart disease (CHD) risk factor levels. Three Afrikaner communities were surveyed before and after a 4-year intervention in two of the communities, the third serving as a control (C). Intervention was primarily by small mass media (low intensity intervention, LII) or by small mass media plus interpersonal intervention to high-risk individuals (high-intensity intervention, HII). After allowing for change in C, significant net reductions in blood pressure, smoking, and risk score were obtained in LII and HII alike. Though the total cholesterol (TC) fell by 10-12%, there was no net reduction in favour of the intervention communities. However, LII and HII resulted in significant increases in high density lipoprotein cholesterol (HDL-C) levels and HDL-C/TC ratios in comparison to C. Overall, the LII community fared almost as well as the HII community, and high-risk individuals did not show a greater change in risk factors than others. We conclude that community-based intervention works, and that in these particular communities a media-based health education programme was more cost-effective than one which adds a greater degree of interpersonal intervention. PMID- 8359959 TI - Snoring, sleep apnoea and cardiovascular risk factors: the MONICA II Study. AB - The objective of this study was to evaluate the cardiovascular risk profile in self-reported snorers and sleep apnoeics in an adult representatively-selected population. A total of 1504 males and females, aged 30, 40, 50 and 60 years were included. The following were measured: snoring, alcohol and tobacco consumption by questionnaire, blood pressure, serum high density lipoprotein (HDL) and total cholesterol. Nocturnal respiration was determined in 748 participants. Respiratory distress index (RDI) was defined as the number of apnoea and hypopnoea lasting longer than 10 seconds per hour sleep. Habitual snoring was reported by 19.1% (9.2-24.2%, aged 30-60 years) of males and 7.9% (3.8-11.7%, age 30-60 years) of females. An RDI > or = 5 was found in 10.9% (7.1-18.3%, age 30-60 years) of males and in 6.3% (5.3-7.6%, age 30-60 years) of females. The following factors were associated with snoring: age (P < 0.02), sex (P < 0.001), body mass index (BMI) (P < 0.0001), alcohol (P < 0.05) and tobacco (P < 0.01) consumption. An RDI > or = 5 was associated with sex (P < 0.001), age (P < 0.05), BMI (P < 0.0001), tobacco (P < 0.02) and alcohol (P < 0.05) consumption. Self-reported snores showed higher systolic (P < 0.001) and diastolic (P < 0.001) blood pressure and total cholesterol (P < 0.001) and a lower HDL (P < 0.001). The participants with RDI > or = 5 showed higher systolic and diastolic blood pressure (P < 0.001) and total cholesterol (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359960 TI - Excess mortality for the unmarried in rural Bangladesh. AB - Prospective data from the Matlab surveillance area in rural Bangladesh, 1974 1982, were used in this study to show that divorced and never-married adults (aged 15-44 years) had significantly higher mortality than their currently married peers with differences in disability status accounting for some of this excess risk. Widowed individuals on the other hand had no excess mortality relative to the currently married. A certain proportion of the sharp reduction in mortality associated with remarriage after divorce for men could be attributed to differences in disability between the remarried group and those who remained divorced. Household economic status indicators could account for little of the excess mortality of divorced and never-married individuals relative to their married counterparts. These findings provide support for the hypothesis that a certain proportion of mortality differentials by marital status in this population can be attributed to selection into marriage and remarriage on the basis of underlying disability status. The evidence for the protective effect of increased economic status associated with the currently married state is less convincing. PMID- 8359961 TI - Patterns of infant mortality from Armenian parish records: a study from 10 countries of the diaspora, 1737-1982. AB - Using parish records from 10 different countries with small Armenian communities, this study compared patterns of infant mortality in these countries over a period of 245 years. Deaths registered as aged < or = 1 year were used to estimate the numerator for the infant mortality rates (IMR) while the denominator was estimated from births in the same year based on baptisms in the appropriate registers. To check on the validity of using the baptisms as the denominator for the IMR, records of infant deaths were linked with the baptismal records. Thus, from a sample of 273 infant deaths 78.4% had a baptismal record in the registers of the same church in which the death was recorded. Of the deaths 60% had a recorded cause of death. Over the past 245 years, IMR have fallen substantially in all parishes. However, there were notable exceptions to this general pattern of declining IMR over time. For example, the IMR was tripled in Palestine during the decade of the First World War, possibly as a result of the influx of refugees deported from Turkey. A study of the seasonal occurrence of the deaths revealed peaking of deaths between May and August, a pattern influenced by the relative importance of gastroenteritis as a cause of death during the summer months in Egypt where the majority of these infant deaths were recorded. A review of the most important causes of death helped identify an outbreak of undetermined cause in Belgrade in 1737 and an outbreak of dysentery deaths in Alexandria, Egypt, in 1909.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359962 TI - Consanguinity as a determinant of reproductive behaviour and mortality in Pakistan. AB - To determine the prevalence of consanguineous marriages and estimate the effects of consanguinity on reproductive behaviour and mortality, household and hospital based surveys were conducted in 11 cities in the Pakistan province of Punjab between 1979 and 1985. The 9520 women interviewed reported 44,474 pregnancies, with data collected on maternal and paternal ages at marriage, abortions/miscarriages, stillbirths and deaths in the first month, at 2-12 months and 2-8/10 years. Six categories of consanguineous marriage were included: double first cousin, first cousin, first cousin once removed/double second cousin, second cousin, bradari (brotherhood) and non-consanguineous. Marriages contracted between spouses related as second cousins or closer accounted for 50.3% of the total, equivalent to an average coefficient of kinship (alpha = sigma piFi) of 0.0280. Unions between close biological relatives were characterized by younger maternal and paternal ages at marriage and reduced spousal age difference, but a longer time to first delivery. Overall, they exhibited greater fertility than non consanguineous couples. Antenatal and postnatal mortality were assessed by consanguinity and age interval. Consanguinity-associated deaths were consistently higher in the neonatal, infant and childhood periods. The consequences of these outcomes on the health of the present and future generations is assessed. PMID- 8359963 TI - Trends in amenable mortality in New Zealand 1968-1987. AB - Trends in amenable mortality rates for Maori and non-Maori New Zealanders were analysed and compared using regression models. The contribution of medical services to the decline in mortality rates was estimated. Mortality from causes amenable to medical intervention declined at a greater rate than non-amenable mortality for both groups. The proportion of the decline in mortality attributable to improvement in the impact of medical services was greater for non Maori than for Maori, especially for females. Maori to non-Maori mortality ratios were greater for amenable than for non-amenable causes, indicating a systematic differential between the two groups in the impact of medical services. There was only a small improvement over the 20 years in the excess of amenable mortality suffered by Maori. The results have implications for the provision of medical services to Maori people. PMID- 8359964 TI - Effect of age, birth cohort and period of death on Italian liver cirrhosis mortality, 1972-1986. AB - Liver cirrhosis is one of the main causes of death in Mediterranean countries. A trend towards a global reduction in the mortality rate has been recently reported. In order to clarify better this trend and in an attempt to hypothesize the future pattern of mortality, we analysed data from 254,834 Italian subjects aged 30-79 who died from liver cirrhosis during the period 1972-1986. We used a log-linear Poisson model to examine the effects of age, calendar period of death and birth cohort. Our data confirm that both in the population as a whole and after stratification for three geographical areas (Northern, Central and Southern Italy) the mortality rate is decreasing. The age-effect analysis showed an exponentially rising effect in the Southern population, in accordance with the viral aetiology of cirrhosis, whereas an increased effect followed by a decreased effect was observed in the Northern and Central population, suggesting the alcoholic aetiology for the disease. The results from the birth-cohort effect suggested that in the Northern and Central populations mortality should continue to decrease over the next decade, possibly due to the implementation of better prevention programmes for cirrhotics and to decreased alcohol consumption in Italy. In the Southern population, however, mortality is still rising and this will probably continue for the next decade, as the generations born between 1940 and 1950 who are at high risk of carrying chronic hepatitis B virus infection, reach the age of higher risk of death from liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359965 TI - Pedal cycling fatalities in northern Sweden. AB - The aim of the study was to elucidate the crash and injury mechanisms in bicycle fatalities in the northern half of Sweden. All available autopsy protocols, hospital records and police reports were scrutinized. In 11 years, 146 bicyclists were fatally injured. The majority of the victims were males (66%) and the median age was 60 years. Most of the crashes (81%) occurred from May through October, during weekdays (84%), and during daylight (86%). Almost all victims (88%) died in a motor vehicle collision, in 21% with a truck. None was wearing a helmet. Poor hearing and cerebral arterosclerosis were probable risk factors among the elderly. Of the victims tested, 10% were under the influence of alcohol, half of whom were involved in single-bicycle crashes. In an additional five cases, the motor vehicle driver was impaired by alcohol. All injuries were due to blunt trauma and 69% of the victims died from head injuries. In 91% of all cases, there was an Abbreviated Injury Scale (AIS) score of the head region of > or = 3. The results indicate that separation of bicyclists from motor vehicle traffic by separate cycling tracks and protection of the head by a helmet would be beneficial. PMID- 8359967 TI - Risks for premature rupture of amniotic membranes. AB - The objective of this study was to test the hypothesis that diverse risk variables including infections during the index pregnancy independently increase the risk of preterm premature rupture of amniotic membranes (PROM) and preterm delivery without PROM. A case-control design was used to study women 15-45 years old who had preterm PROM, full-term PROM or preterm without PROM and were singly matched by age race and parity to controls who delivered full-term infants. The odds for preterm PROM was 6.0 times that of controls among women with intra amniotic infection, 3.7 times among those with urinary tract and 7.6 times among women with gonorrhoea infections after controlling for the effects of exposure to cigarette smoke, having previous preterm and full-term PROM deliveries and antepartum bleeding that independently increased the odds. The odds for preterm births without PROM was 4.8 times that of controls among women with a previous preterm PROM birth, was significantly increased among those exposed to cigarette smoke or having antepartum bleeding, but not among those exposed to chlamydia infection. Even after adjusting for concomitant risk factors, women with preterm PROM births were more likely than their matched controls to have had infections. PMID- 8359966 TI - Risk factors for preterm delivery in Burkina Faso (west Africa). AB - The environmental and socioeconomic risk factors for preterm delivery were assessed in a West African urban population (Bobo-Dioulasso, Burkina Faso). The study population were 102 cases of preterm delivery matched with 102 controls obtained from 4124 sequential deliveries which occurred between May and October 1989 in the three maternity centres in the city. The univariate analysis identified the risk factors as age (< 20 years), primiparity, marital status (single), low frequency of antenatal visits, death of a previous child and level of education of the mother. The following risk factors identified by multivariate analysis (logistic regression) are consistent with those identified in previous studies: youth of the mother, primiparity (P = 0.01) and death of a previous child (P < 0.05). On the other hand, in this study, the level of education of the parent was identified as an independent risk factor (P < 0.001). This finding could be used to determine a target population for prevention programmes. PMID- 8359969 TI - Development and validation of a food frequency questionnaire in Spain. AB - To create a suitable instrument to estimate intakes of total calories, protein, carbohydrate, fats (saturated, mono and polyunsaturated), alcohol, cholesterol, fibre, vitamin A and vitamin C in epidemiological studies conducted in Spain, a food frequency questionnaire was developed and tested. In particular, the questionnaire was designed to be used in a large population-based case-control study of dietary factors in relation to breast and colorectal cancer among women from different Spanish regions. After identifying the most important food sources of the relevant nutrients in the study population, the final version of the questionnaire asked about consumption of 118 food items. Its reproducibility and validity were tested among 147 Spanish women aged 18-74 years. These subjects were asked to complete the questionnaire before and after completing four 4-day food records. The records were obtained at 3-month intervals designed to represent daily and seasonal changes (between 1990 and 1991). Using the information available from standard Spanish food composition tables, an ad hoc computer program was created to translate food consumption into nutrient intake. The reproducibility of the questionnaire was assessed by means of estimating correlations between nutrient scores measured with the same instrument twice, with a period of 1 year between estimates. Pearson correlation coefficients ranged from 0.51 for saturated fat to 0.88 for alcohol. In the validity study, correlation coefficients between diet records and the first and second questionnaires ranged between r = 0.20 for vitamin A and r = 0.88 for alcohol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359968 TI - An outbreak of pellagra related to changes in dietary niacin among Mozambican refugees in Malawi. AB - Between February and October 1990, 18,276 cases of pellagra dermatitis (due to niacin deficiency) were reported among 285,942 Mozambican refugees in Malawi. Overall, 6.3% of the refugee population developed pellagra and the attack rate was 7.8 times higher among women than men. This outbreak followed a 5-month cessation of groundnut distribution (the major source of niacin) to refugees. A matched-pair case-control study confirmed the protective role of the daily consumption of groundnuts (Odds Ratio [OR] = 0.08), as well as the independent role of garden ownership (OR = 0.34), and home maize milling (OR = 0.3). Recommended corrective action included early case finding and treatment, distribution of niacin tablets, prompt identification of groundnut supply on the world market, fortification with niacin of the food ration and diversification of the food basket through access to local markets. PMID- 8359970 TI - Short-term and long-term reproducibility of dietary history interview data. AB - This study gives results for comparisons between dietary history interviews repeated at short-term (4-8 months) and long-term (4-7 years) intervals in conjunction with the Finnish Mobile Clinic Health Examination Survey. Interviews surveying the whole range of consumable foods over the preceding year were completed in 1967-1976. Short-term study was accomplished among 93 adults, and long-term study among 1844 adults. Comparisons were made for intakes of 32 food groups and 32 nutrient indices. In the short term, the intraclass correlation coefficients for nutrient indices ranged from 0.16 to 0.80, with 90% of values higher than 0.5. The corresponding figures for repeated measurements at long-term interval were generally poorer, being in the range 0.12-0.60, with 45% of values > 0.5. When studied in population subgroups, long-term agreement in dietary data was not found to be affected by sex, age, body mass index or smoking status, but it may be reduced among heavier drinkers (> or = 20 g alcohol per day). The intraclass correlation coefficients for separate nutrients tended to be higher than those for different food groups. In conclusion, we suggest that the reproducibility of the dietary history method used was acceptable, and that the dietary patterns of examinees were sufficiently stable to be compatible with the needs of epidemiological follow-up studies. PMID- 8359971 TI - Incidence of HIV-1 infection among adults in the Kagera region of Tanzania. AB - The results of a population-based follow-up study are presented. The baseline study which started in August 1987, was carried out to determine the prevalence of human immunodeficiency virus (HIV-1) infection in the Kagera region of Tanzania. A multistage cluster sampling technique was adopted in the selection of the study population. In the follow-up survey which started in June 1988, members of the same study population were revisited and studied in order to determine the incidence of HIV-1 infection among those who were HIV seronegative in the initial survey. HIV serology was conducted by using enzyme-linked immunosorbent assay and all positive sera were confirmed by the Western blot technique. A total population of 1316 adults aged 15-54 years was studied, constituting an average follow-up response rate of 69% in the rural areas and of 59% in the urban area. The overall incidence of HIV-1 infection among the adult population sample was 13.7 per 1000 person-years at risk with the highest incidence in the urban zone (47.5 per 1000 person-years at risk) and the lowest incidence in one of the three rural zones (4.9 per 1000 person-years at risk). The age-specific annual incidence was highest in the age group 25-34 years for males and in the age group 15-24 for females. From these results it was estimated that the number of newly infected adults in the region each year is about 8200 with a range between 5400 and 11,000 corresponding to the 95% confidence limits on the overall incidence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8359972 TI - Determinants of HIV-1 infection in intravenous drug users in Valencia, Spain, 1987-1991. AB - From 1987 through 1991, 2687 intravenous drug users recruited at three AIDS information centres in the Region of Valencia (Spain) were interviewed about drug use and sexual behaviour and subsequently tested for HIV-1 antibody. The overall seroprevalence was high, 50% (95% confidence interval [CI]: 41.8-51.9%). There were no differences by gender, but HIV-1 infection was related to older age and city of residence. After adjustment by means of logistic regression age (odds ratio [OR] = 1.80), sharing of injection equipment (OR = 2.16), duration of addiction (OR = 6.59) and prostitution (OR = 1.77) were significantly associated with HIV-1 prevalence. High educational level was inversely related to HIV-1 status (OR = 0.43) and a decreasing trend of prevalence with time was observed. PMID- 8359973 TI - Acceptability of the tuberculosis service: scale development. AB - Health workers require reliable, easily administered and scored measures to evaluate acceptability of a health service. A 13-item attitude scale was developed to determine acceptability of the tuberculosis (TB) service. The objectives of this study were to: ascertain reliability (internal consistency) of the scale and confirm, through factor analysis, that acceptability of the TB service was based on cognitive and affective reactions. The sample comprised 487 black adult interviewees (67 TB patients on ambulatory therapy and 420 non-TB community members) from two urban townships in the Transvaal, South Africa. The reliability coefficient revealed a high level of internal consistency for the scale (r = 0.84). A principal components analysis, with orthogonal and oblique rotations, was conducted. Two factors accounted for 45.4% of the variance. The highest loadings on Factor I involved an empathic dimension (friendly, helpful, encouraging and communicative). Factor II tended to focus on the organizational elements of the system, such as availability, consistency of information, length of waiting time and maintenance of contact. It was concluded that this scale was a reliable, easily administered and scored measure of acceptability, with underlying affective and cognitive components. PMID- 8359974 TI - A clinical prediction rule for American cutaneous leishmaniasis in Colombia. AB - Neither parasitological nor molecular diagnosis of leishmaniasis is widely available in clinical settings where American cutaneous leishmaniasis (ACL) is endemic. Therefore four clinical prediction rules for ACL were developed which incorporated physical examination findings (clinical rule), physical examination and leishmanin skin test (LST) (clinical-LST rule), physical examination and historical information (clinical-historical rule), or physical examination, historical information and LST (clinical-historical-LST rule). One hundred parasitologically diagnosed ACL cases and 38 cases of chronic skin lesions of other aetiologies comprised the derivation set. The validation set consisted of 124 ACL cases and 35 patients with lesions of other aetiologies. Components of each rule were selected by bivariate analysis, then step-wise logistic regression. Sensitivity, specificity and efficiency were calculated for each score threshold; the threshold achieving greatest efficiency was selected for each rule. When these rules were applied to the validity set the sensitivity, specificity and efficiency were respectively: clinical 93%, 31%, 79%; clinical LST 90%, 73%, 85.9%; clinical-historical 97%, 51%, 87%; clinical-historical-LST 92%, 70%, 87%. Inclusion of LST skin test consistently improved the specificity of the rules. Should a given clinical setting warrant optimizing either sensitivity or specificity alone, the rule thresholds can be adjusted. These and other prediction rules, once evaluated in other settings, should be incorporated into leishmaniasis control programmes. PMID- 8359975 TI - Ascertainment corrected rates: applications of capture-recapture methods. AB - Accurate rates, though fundamental to epidemiology, are often very difficult to obtain. Incidence, prevalence, and mortality rates have traditionally been established through either passive reporting surveillance systems, through active surveillance systems, or by a combination of the two methods. Typically, when researchers employ these approaches they do not formally evaluate or correct for the degree of underascertainment. Undercount of cases is a potent determinant of rates which we cannot continue to ignore. We believe all rates should be adjusted for underascertainment in order to achieve a truer picture of the risk and risk factors of disease. Here, we present a procedure to ascertainment correct rates based upon well established capture-recapture methods. PMID- 8359976 TI - HIV and AIDS indexed by MEDLINE. PMID- 8359977 TI - Intention-to-treat analyses in clinical trials and cohort studies. PMID- 8359978 TI - Reduced transport of adenosine in erythrocytes from patients with beta thalassaemia. AB - The transport of adenosine into blood from beta-thalassaemia subjects was measured to provide a background to the relationship between resistance of malaria infection and beta-thalassaemia. Adenosine transport was significantly reduced in the abnormal cells in the blood samples. As adenosine is one of the major purines salvaged by P. falciparum malaria, we suggest that the resistance to malaria in beta-thalassaemia subjects may be due to a nutrient deficiency in the abnormal red cells. PMID- 8359979 TI - Differential secretion of acetylcholinesterase and proteases during the development of Heligmosomoides polygyrus. AB - The development of the gastrointestinal nematode Heligmosomoides polygyrus was studied in the mouse. Levels of production of acetylcholinesterase and proteases were measured in excretory/secretory products of various stages of the parasite. The production of acetylcholinesterase was found to be maximal between days 4 and 6 post-infection, corresponding to the fourth larval stage of the parasite's life cycle. Analysis of proteolytic activity revealed both quantitative and qualitative differences between the stages. Quantitative examination showed a maximal concentration of proteolytic enzymes in the early third larval stage (L3). Qualitative analysis revealed L3-associated molecules at 96, 15 and 8 kDa, L4-associated molecules at 58 and 33 kDa and adult-associated molecules at 116, 102, 39 and 25 kDa. A number appeared to be shared by all stages (18, 16 and 13 kDa), whilst others (76 and 42 kDa) appeared to be associated with the late L4/early adult parasite. The biological and immunological implications of variation in the production of proteases and acetylcholinesterase during the development of H. polygyrus are discussed. PMID- 8359980 TI - Anthelmintic effects of cyclosporin A on protoscoleces and secondary hydatid cysts of Echinococcus granulosus in the mouse. AB - Cyclosporin A (CsA), employed primarily as an immunosuppressant during the management of organ and graft transplants, exhibits anthelmintic properties. However, its efficacy against tapeworm infections in laboratory models is variable. A preliminary investigation has been undertaken to assess the action of CsA on the establishment and growth of protoscoleces and secondary hydatid cysts of ovine Echinococcus granulosus in mice. Administration of CsA in five consecutive daily doses, beginning 2 days prior to infection, resulted in significant reduction in cyst establishment (measured in terms of cyst masses, cyst numbers and cyst wet weights), when mice were autopsied 20 weeks post infection. None of these parameters were significantly reduced when the drug was administered 18 weeks post-infection, although wet weight decreased by 42%. Ultrastructural examination of the germinal membrane and laminated layer of late treated E. granulosus revealed abnormalities in all cysts studied whereas control and early-treated hydatids were normal. A case is made for the consideration of a clinical use for CsA for post-operative control of secondary hydatidosis and its efficacy against hydatid cysts is discussed. PMID- 8359981 TI - Comparative pharmacokinetic behaviour of albendazole in sheep and goats. AB - Albendazole (ABZ) containing a trace of [14C]-ABZ was administered intraruminally at 4.75 mg kg-1 to Merino sheep and Angora goats and the pharmacokinetic behaviour of ABZ and its metabolites in plasma nd abomasal fluid compared. The systemic availability (area under the curve, AUC) for total [14C]-labelled metabolites was significantly lower in goats than in sheep. This was largely attributable to the disposition of ABZ sulphoxide (ABZ.SO) which had a significantly lower maximum concentration (Cmax) in goats (0.94 +/- 0.04 micrograms ml-1) than in sheep (1.41 +/- 0.24 micrograms ml-1). The AUC of [14C] in abomasal fluid was similar in goats and sheep, with approximately 35 and 45% of the dose passing the pylorus in the two species, respectively. ABZ, ABZ.SO and ABZ sulphone (ABZ.SO2) were present in the abomasal fluid of both species but between-species differences were only evident with ABZ.SO which had a lower Cmax in goats compared with sheep. The relative proportions of the [14C] dose excreted in urine and faeces were similar between species. It is suggested that ABZ may be sequestered to a greater extent in the liver of goats than of sheep which would result in lower concentrations of ABZ.SO in plasma and abomasal fluid. This behaviour might be compensated for by administering ABZ to goats at a proportionally higher dose rate. PMID- 8359982 TI - Cellular and chemical mediators of type 1 hypersensitivity in calves infected with Ostertagia ostertagi: mast cells and eosinophils. AB - Abomasal mucosal mast cell and eosinophil accumulation was morphometrically evaluated in 26 Holstein steers after natural or experimental infection with Ostertagia ostertagi. Results showed that following infection, accumulation of mast cells and eosinophils in abomasal tissue was dependent on infection pattern. Eosinophilia was greater in steers with type 1 ostertagiosis, while mastocytes was more pronounced in steers with type 2 ostertagiosis. PMID- 8359983 TI - Cellular and chemical mediators of type 1 hypersensitivity in calves infected with Ostertagia ostertagi: histamine, prostaglandin D2, prostaglandin E2 and leukotriene C4. AB - Plasma histamine, prostaglandin E2 (PG) D2, PGE2, and leukotriene (LT) C4 levels were determined in 26 Holstein steers before and after natural or experimental infection with Ostertagia ostertagi. Post-infection abomasal lymph was also assayed for PGD2, PGE2, and LTC4. Histamine determinations were performed on abomasal tissue from three locations. Results showed that: (1) tissue histamine levels increased in steers with type 2 ostertagiosis, (2) lymphatic PGD2 and PGE2 levels were increased, probably as a result of macrophage activity, (3) lymphatic LTC4 levels increased in steers with type 1 ostertagiosis, and were correlated with tissue eosinophilia, and (4) plasma levels of PGD2, PGE2, LTC4 and histamine were not useful for predicting worm burdens. These findings suggest a functional role for eosinophils and mast cells in the pathophysiology of ostertagiosis, through mediation of a type 1 hypersensitivity reaction. PMID- 8359984 TI - Cercariae and metacercariae of Stephanostomum cloacum (Trematoda: Acanthocolpidae). AB - Cercariae and metacercariae of the acanthocolpid trematode, Stephanostomum cloacum (Srivastava, 1938) are described and illustrated, based on material collected from Chilka Lake, a brackish water lagoon. Natural infections with the cercariae were found in the snail, Nassarius orissaensis and with the metacercariae in the bivalve, Modiolus undulatus. Cercariae are distomate, ophthalmoxiphidiocercous, and possess a small stylet, simple tail, four pairs of penetration glands arranged in two groups and a large granular excretory bladder. Development of the cercaria into the metacercaria was followed in M. undulatus under laboratory conditions. Infections with adults of S. cloacum were identified in the fish Triacanthus biaculeatus, found in the lake. PMID- 8359985 TI - Serum-independent and serum-dependent cytoadherence in the interaction of Entamoeba histolytica with mammalian target cells. AB - Entamoeba histolytica kills target cells only on direct contact, suggesting that trophozoite-mediated cytolysis is initiated by the contact between trophozoites and target cells. We have shown that adherence between E. histolytica and target cells (polymorphonuclear granulocytes, erythrocytes, Chinese hamster ovary cells, human colon carcinoma cells) was inhibited by specific carbohydrates, and adherence between E. histolytica and polymorphonuclear granulocytes (PMN) was enhanced by preincubation of the trophozoites with serum. Inhibition of adherence clearly paralleled inhibition of cytolysis and phagocytosis of target cells. Cytolysis of PMN, however, was not increased by preincubation of the trophozoites with serum. These results suggest that the effector functions of trophozoites are only dependent on carbohydrate-specific adherence mechanisms mediated by the amoebic Gal/GalNAc-binding lectin. E. histolytica trophozoites themselves can be killed by PMN, depending on the virulence of the trophozoites. PMN could not kill E. histolytica trophozoites more effectively when the adherence was enhanced by preincubation of the trophozoites with serum or when adherence was only mediated by serum-dependent mechanisms. PMID- 8359986 TI - In vitro activity of paraherquamide against the free-living stages of Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia circumcincta. AB - Paraherquamide, an oxindole alkaloid recently reported to have potent nematocidal activity, was shown to have a marked inhibitory effect on the motility of the free-living larval stages of H. contortus, T. colubriformis and O. circumcincta. The effect of paraherquamide on larval motility could be distinguished from that caused by levamisole and the avermectins. After 72 h exposure, the concentration of paraherquamide required to inhibit the motility of 50% of L3 larvae present was 0.033, 0.058 and 2.7 micrograms ml-1 for O. circumcincta, T. colubriformis and H. contortus, respectively. Ivermectin (IVM)-resistant isolates of H. contortus were significantly more sensitive to the paralytic effects of paraherquamide than IVM-susceptible isolates of this species. Paraherquamide had no effect on the time for development from the egg to the L3 larval stage of H. contortus, T. colubriformis and O. circumcincta. PMID- 8359987 TI - The diagnostic antigen encoded by gene fragment Dv3-14: a major sperm protein of Dictyocaulus viviparus. AB - The Dv3-14 gene fragment of Dictyocaulus viviparus is 471 bp, of which about 90% is translated. The calculated molecular mass of the translation product is 15.5 kDa. DNA sequence homologies were found with major sperm proteins (MSPs) from Ascaris suum, Caenorhabditis elegans and Onchocerca volvulus. Within a segment of 62 amino acids the predicted amino acid sequence of Dv3-14 shows 84% homology with an A. suum MSP and 84% homology with a C. elegans MSP. Computer analysis of the protein sequence identified three segments of immunodominant antigenic sites as putative candidates for synthetic peptide antigens. Immunoblotting analysis of the translated product showed that it is adult stage specific, water soluble and not membrane bound and can be demonstrated in the supernatant fluids of cultures from adult worms kept in cell culture medium. The results suggest that the protein encoded by Dv3-14 is a MSP of D. viviparus. PMID- 8359988 TI - Comparative histopathology of Longicollum (Acanthocephala: Pomphorhynchidae) infection in the alimentary tract and spleen of Acanthopagrus australis (Pisces: Sparidae). AB - The pomphorhynchid acanthocephalan Longicollum alemniscus infected the rectum of 16 and the intestine of five of 628 Acanthopagrus australis from Moreton Bay, Queensland. The neck and proboscis penetrated the entire gut wall and were surrounded by a layer of compact, rounded fibroblasts inside a layer of elongated fibroblasts and scattered connective tissue fibres. These layers extended across the entire gut wall and into the capsule that enclosed the proboscis outside of the gut. A similar parasite occurred extraintestinally in three fish; the proboscis of one penetrated into the spleen. The spleen was shrunken, with the proboscis and anterior part of the neck enclosed in a capsule of proliferated connective tissue and cellular elements similar to that in the response to infection of the gut wall. PMID- 8359989 TI - The toxicity of antifolates in Babesia bovis. AB - A variety of anti-folate compounds have been tested for their ability to inhibit the growth of Babesia bovis as measured by the incorporation of [3H]hypoxanthine into the parasite's nucleic acids. Inhibitors of folate synthesis (including 7 methylguanosine and several sulpha drugs) were without effect but several structural analogues of folate were toxic. The most potent folate analogues were the lipophilic compounds piritrexim and trimetrexate, each causing 50% inhibition of [3H]hypoxanthine incorporation (IC50) at a concentration of 2.9 nM; other classical anti-folates such as pyrimethamine, methotrexate and trimethoprim were at least 100-fold less effective with IC50 values of 1.2, 0.29 and 0.50 microM, respectively. From these results we conclude that B. bovis does not synthesize folate de novo under cell culture conditions. However, the toxic effects of piritrexim and trimetrexate suggest that dihydrofolate reductase (DHFR) activity is essential for the parasite, most probably because of the role of this enzyme in the synthesis of thymidine nucleotides via thymidylate synthase. PMID- 8359990 TI - Analysis of the results obtained using a technic of experimental primary infestation with Fasciola hepatica in the rat. AB - In this work, we analyzed the results obtained using a technic of infestation with Fasciola hepatica in the rat. The infestations were carried out with 30 metacercariae in a gelatin capsule. The humoral immune response, measured by ELISA, and the liver necroses, spleen size, number and length of the flukes recovered at necropsy were followed during the course of four experimental primary infestations. The results showed that the magnitude of the parasitic burden did not correlate with the humoral immune response of the rat. The study of the liver necroses, spleen size, fluke length and antibody titres showed that the use of 30 metacercariae in a capsule as a technic of infestation in the rat ensured the homogeneity of the parasite development and the humoral immune response of the host. PMID- 8359991 TI - Female-specific genomic PCR sequences from Schistosoma mansoni as probes for hybridization histochemistry. AB - Rapid methods for sexing single larval or egg stages of schistosomes have been difficult to establish. Such methods would be of value for assessing changes in sex ratios at different stages of the life cycle and studying diseases processes of schistosomiasis. We describe the use of hybridization histochemistry for identification of female eggs of Schistosoma mansoni in sections of infected mouse liver using a highly repetitive genomic DNA sequence generated by the polymerase chain reaction with primers spanning a known female-specific sequence (W1) of S. mansoni. In an initial study, approximately half of the eggs in each liver section from mice infected for 50 days labelled heavily with this probe. Further studies will evaluate the sensitivity and specificity of the probe on clonal populations (either male or female) or larvae in host tissue. PMID- 8359992 TI - An outbreak of haemonchosis associated with anthelmintic resistance in sheep. AB - An outbreak of haemonchosis associated with anthelmintic resistance was recorded in a flock of 150 crossbred lambs. Closantel and ivermectin were 100% effective against Haemonchus contortus while fenbendazole and morantel reduced faecal egg counts by 87 and 29%, respectively. Levamisole showed an efficacy of 95%. At double the recommended dose (10 mg kg-1), fenbendazole had an efficacy of 99% against H. contortus infection. This appears to be the first report of an outbreak of haemonchosis associated with fenbendazole and morantel resistance in a strain of H. contortus in sheep. PMID- 8359993 TI - New host record for the entodiniomorphid ciliate, Troglodytella abrassarti, from siamangs (Hylobates syndactylus). AB - Examination of faecal samples from several diarrhoeic siamangs Hylobates syndactylus (Anthropoidea: Hylobatidae) revealed the presence of numerous entodiniomorphid ciliates whose morphological and ultrastructural characteristics were consistent with those of Troglodytella abrassarti previously recorded from chimpanzees, orangutans and gorillas (Anthropoidea: Pongidae). PMID- 8359994 TI - Species-specific PCR for the parasitic nematodes Haemonchus contortus and Trichostrongylus colubriformis. AB - Reliable species determination of gastrointestinal nematode parasites from sheep is usually carried out on third-stage larvae (L3) by visual differentiation. The culturing of L3 takes about 1 week so a reliable method that could use eggs for the determination would accelerate the procedure. We developed a polymerase chain reaction (PCR), using very small amounts of parasite DNA and an oligonucleotide set according to parts of the DNA sequence of a beta-tubulin gene from Haemonchus contortus, that can discriminate H. contortus DNA and Trichostrongylus colubriformis DNA from each other and from several other sheep nematode parasites. This method can be used for every stage of the parasite, including eggs. For the first time a PCR method is reported to discriminate between sheep nematode parasites. PMID- 8359995 TI - Comparison of the second internal transcribed spacer (ribosomal DNA) from populations and species of Fasciolidae (Digenea). AB - The nucleotide sequence of the 3' end of the second internal transcribed spacer region (ITS2) was determined for four isolates of Fasciola hepatica, two isolates of Fasciola gigantica, one isolate of Fascioloides magna and one isolate of Fasciola sp. from Japan. Intraspecific sequence divergence was negligible. Sequence divergence between F. hepatica and F. gigantica was 2.8% and between Fasciola hepatica and Fascioloides magna was 13.2%. The sequence of Fasciola sp. from Japan matched closely that of F. gigantica. This study demonstrates variability in nucleotide sequence within the ITS2 region which allows discrimination between species of Fasciolidae. PMID- 8359996 TI - Experience with doxorubicin-bound polyisohexylcyanoacrylate nanoparticles on murine alveolar echinococcosis of the liver. AB - The parasiticidal properties of doxorubicin against the metacestode of Echinococcus multilocularis were investigated after binding of that drug to polyisohexylcyanoacrylate nanoparticles, a colloidal biodegradable drug carrier. A reduction of the hepatic parasite development and a reduced viability of the metacestode were observed in mice injected with 5 mg kg-1 body weight-1, but 7.5 mg kg-1 body weight-1 did not appear more efficient. Free doxorubicin or unbound nanoparticles had no antiparasitic activity. PMID- 8359997 TI - Psychiatric manifestations of olivo-ponto-cerebellar atrophy and treatment with clozapine. AB - Patients with multiple system atrophy, a neurodegenerative disease entity, have a high incidence of associated mental disturbances such as a mood disorder with or without psychotic features. Treatment of the psychiatric symptoms, without compromising neurological status, is often complicated and unsuccessful. This article describes a patient with olivo-ponto-cerebellar atrophy and treatment resistant psychotic depression whose psychiatric symptoms were successfully treated with clozapine without aggravating the neurological disabilities. PMID- 8359998 TI - Psychologic distress during menopause: associations across the reproductive life cycle. AB - OBJECTIVE: To determine if women with high psychologic distress attending a menopause clinic report more previous psychiatric disorders (especially depression), or psychologic distress associated with oral contraceptive use and reproductive cycle events than women with low psychologic distress attending the clinic. METHOD: Consecutive women attending a university hospital menopause clinic were administered the Brief Symptom Inventory (BSI). Women with high psychologic distress (who met case severity on the BSI general severity index) were compared to a similar number of the lowest scoring clinic women on their reports of previous psychiatric diagnoses and treatment, and depression or distress related to oral contraceptive use, the premenstrual period, or associated with pregnancy. RESULTS: The forty-four women with high psychologic distress were significantly more likely than the forty-two menopause clinic patients with low psychologic distress to report a past psychiatric diagnosis (usually depression) (p = 0.001), requiring anti-depressant treatment (p = 0.002), oral contraceptive dysphoria (p = 0.004), dysphoric premenstrual syndrome (p = 0.000), postnatal blues (p = 0.02) and postpartum depression (p = 0.004). CONCLUSIONS: Although the halo effect of current distress or retrospective reporting may have biased these results, the similarity of ratings in the two groups on physical symptoms in menopause and psychologic symptoms during pregnancy makes this less likely. These findings corroborate other recent studies showing that women who suffer from affective disorders following one reproductive event are more vulnerable to recurrences associated with others. Clinicians should inquire about possible relationships between previous depression or psychologic distress and reproductive cycle events as it may help predict women who are vulnerable to affective disorders and psychological distress at these critical times. PMID- 8359999 TI - Body image in chronic illness--a reconceptualization. AB - OBJECTIVE: Was to construct a classification system of the body image specifically relevant to patient experience of chronic physical disorder. METHOD: To review both previous writings on body image and also data on psychosocial factors relevant to a variety of chronic illnesses. From this were derived four component parts of body image: comfort, competence, appearance and predictability. These are discussed in general and disease-specific terms. RESULTS: Using this format, a classification system is offered. This is intended to be simple enough for routine clinical use and yet to offer some insight into body experience. An example is given. CONCLUSION: Separating out the aspects of body image relevant to physical illness provides a clinically useful classification system. Further work is needed to determine its applicability as a research tool. PMID- 8360000 TI - New perspectives on Type A behavior: a psychiatric point of view. AB - OBJECTIVE: To propose an answer to Medicine's confusion about what Type A Behavior is. METHOD: To critically review early writings about Type A as well as current literature with a focus on five key articles which are frequently mentioned in medical and lay literature as containing relevant data undermining the Type A hypothesis. These five are critically evaluated for their definition of Type A, method of diagnosing Type A, nature of the cohort studied, and logic of their conclusions. RESULTS: There is a failure in the literature to distinguish between Axis I symptoms and Axis II personality traits; the same term, Type A, being applied to quite different phenomena. CONCLUSIONS: Type A should be defined as a Axis II Personality Disorder, and a new term, Stress Disorder (or Hostility Disorder) to the Axis I symptoms. This opens up endless possibilities in Medicine for Stress Disorder research, since Medicine can rightly argue that the research is to better treat the Stress Disorder disease, that precedes Coronary Artery disease. PMID- 8360001 TI - Self-reported compliance with diabetes self-management during pregnancy. AB - OBJECTIVE: The current study examined regimen compliance in pregnant women with pre-existing (overt) diabetes across multiple self-care tasks at three times during the pregnancy: mid-second, early third, and late third trimesters. METHOD: Forty-nine pregnant women with Type I (68%) or Type II (32%) diabetes completed measures to assess compliance with the diabetic regimen, major and minor life stressors, and social support for the diabetic regimen. RESULTS: Pregnant women with overt diabetes generally reported being compliant with their self-care regimen. There were, however, notable differences in reported compliance levels across different regimen tasks. Specifically, 74 to 79 percent of women reported being always compliant with dietary recommendations compared to 86 to 88 percent for insulin administration, 85 to 89 percent in managing insulin reactions, and 94 to 96 percent for glucose testing. Furthermore, stress in the form of major and minor life events and regimen-related social support were significantly related to self-reported compliance with dietary recommendations. There was no relationship between compliance and blood glucose levels. CONCLUSIONS: These findings suggest that psychiatric consultants focus on ways to increase social support as one means of improving compliance in pregnant women with diabetes. PMID- 8360002 TI - How big was the effect? PMID- 8360003 TI - Psychosocial factors and recurrent genital herpes: a review of prediction and psychiatric treatment studies. AB - OBJECTIVE: The purpose of this review was to evaluate the evidence which supports the association between psychosocial factors and genital herpes simplex virus recurrences (HSV), as well as to examine the biological and psychological treatments for disease. METHOD: Forty-five studies were reviewed from the years 1928 to 1991. Studies were identified via computerized biographic literature search of Psychological Abstracts and Medline. Additional studies were located by inspection of key article reference sections. Studies were included in the review if the sample consisted of recurrent genital herpes sufferers and the design was either correlational or experimental. Cases studies were reviewed if they described HSV psychiatric treatment and provided outcome information. RESULTS: Psychosocial variables are important elements in the prediction, maintenance, and management of recurrent genital herpes. Furthermore, the effectiveness of psychological treatment regimes may be explained via psychoimmunological theory. CONCLUSIONS: Psychosocial treatment should be considered as adjunctive therapy for biological treatment of recurrent HSV infections. Future research should address primary prevention of genital herpes and other sexually transmitted diseases, including HIV infections. PMID- 8360004 TI - Guided tissue regeneration and endosseous dental implants. AB - This paper presents an evaluation of the use of the principles of guided tissue regeneration to correct the osseous defects associated with the placement of dental implants. The biologic rationale for the use of supplemental materials, such as decalcified freeze-dried bone allograft, is discussed. The results of this investigation suggest that the use of a physical barrier in combination with a bone allograft can produce successful results in 97% of the defects treated. PMID- 8360005 TI - Autogenous tooth transplantation: a reevaluation. AB - This paper discusses whether autogenous tooth transplantation can survive as an option in the future dental armamentaria. Clinically, successful transplants must show a radiolucent space between the roots and surrounding bone. There must be no evidence of ankylosis, no permanent root resorption, and no inflammation. Histologically, the criterion of success is a normal and functional periodontal ligament between the root surfaces of transplants and the bone or gingival connective tissues. Case reports are presented to illustrate replantation or transplantation of teeth. Possible donor teeth are those with the proper amount of viable periodontal ligament, single-rooted teeth, third molars, and malpositioned or impacted teeth. The transplantation procedure involves extraction of the donor tooth, measurement of the root form and amount of periodontal ligament, preservation of donor tooth, preparation of recipient socket, positioning of donor tooth, suturing, and temporary splinting. PMID- 8360006 TI - Gingival response to subgingival placement of monolithic tetracycline-impregnated fibers: microscopic observations. AB - This study examines and characterizes the soft tissue wall of periodontal pockets after a 10-day in vivo exposure to monolithic tetracycline-impregnated fibers, with and without root planing. Four teeth from each of eight patients were randomly assigned to (1) nontreatment (controls), (2) treatment by root planing only, (3) treatment by tetracycline fiber only, or (4) treatment by scaling and root planing and tetracycline fibers. Ten days after initial therapy, all teeth were extracted with associated soft tissue pocket walls intact. Three specimens were obtained from each tooth for examination by scanning microscopy, energy dispersive spectroscopy, and light microscopy. Results indicated that use of tetracycline-impregnated fibers over a 10-day period did not adversely affect the epithelial lining and had no significant effect on the density or character of the inflammatory response present in adjacent soft tissue and confirmed the antimicrobial effects of the fibers. PMID- 8360007 TI - Guided tissue regeneration without a stage 2 surgical procedure. AB - In the two cases described, the problems of insufficient bone and insufficient soft tissue in the edentulous ridge were addressed concurrently. Freeze-dried demineralized bone was used to fill the osseous defect. Freeze-dried fascia lata was used to prevent epithelial migration into the defect, act as a barrier, and eliminate a second surgery for membrane removal. This regeneration procedure can provide increased alveolar bone for better implant placement and esthetics. PMID- 8360008 TI - The strip gingival autograft technique. AB - In keeping with the concept of rapid epithelialization of close wound edges, the strip technique was developed to maximize the area of gingival grafting with less trauma to the donor site or the recipient site. An incision is made and a partial thickness flap is reflected so that stable periosteum is left. The apical mucosal border of the recipient site is sutured to the periosteum. Donor tissues are obtained in 2-mm-wide strips, transferred to the recipient site, and sutured. Dry foil and surgical packing are used to stabilize and protect the site during healing. The donor site is rapidly epithelialized (within 10 days) and produces minimal patient discomfort. PMID- 8360009 TI - The effect of citric acid application on periodontally involved root surfaces. II. An in vitro scanning electron microscopic study. AB - The in vitro effect of citric acid application on periodontally involved root surfaces was investigated using scanning electron microscopy. Teeth were selected following specific criteria. The specimens were prepared for observation, and the features of the root surface were studied. The results demonstrated that a 3 minute application of citric acid (pH = 1.0) to the root surface after scaling and root planing demineralized the outer root surface, opened the dentinal tubules, and exposed collagen fibers. Scaling and root planing alone left the surface with a smear layer, scattered islands of cementum, and no collagen fibers or exposed dentinal tubules. PMID- 8360010 TI - Histogenesis of the avian retina in reaggregation culture: from dissociated cells to laminar neuronal networks. PMID- 8360011 TI - Plasticity and differentiation of retinal precursor cells. PMID- 8360013 TI - Growth factor-induced retinal regeneration in vivo. AB - It is apparent from a number of studies that the RPE has a remarkable ability to regenerate neural retina. While retinal regeneration from the RPE has not been reported in adult vertebrates, with the exception of the newt, there is evidence that many vertebrate species have the ability to regenerate a new neural retina during the early development. Studies of retinal regeneration in the chicken embryo have provided some insight into the requirements for this process. Recent investigations using copolymer implants as an intraocular delivery system for growth factors have demonstrated that the state of differentiation of RPE cells in the stage 22-24 chicken embryo can be altered in vivo by specific growth factors, aFGF and bFGF. These results raise the distinct possibility that variations in the local production of FGFs and their receptors in the eye during development may, in part, regulate the pathway of differentiation of RPE and neural retina precursors. Further research on the role of FGFs and their receptors in retinal development and regeneration will not only contribute to our understanding of how the differentiated state is achieved and maintained but may provide a foundation for future attempts to develop methods of treatment for various degenerative and proliferative diseases of the eye. PMID- 8360012 TI - Genetics, development, and malignancy of melanocytes. PMID- 8360014 TI - Cytokine production by retinal pigmented epithelial cells. PMID- 8360015 TI - Biological clocks in the retina: cellular mechanisms of biological timekeeping. PMID- 8360016 TI - Type IV collagen, laminin, and fibronectin promote the adhesion and migration of rabbit lens epithelial cells in vitro. AB - PURPOSE: To assess the ability of basement membrane and extracellular matrix proteins to promote rabbit lens epithelial cell adhesion and migration, which may play a role in the development of secondary cataract. METHODS: Rabbit lens epithelial cells were isolated and grown in tissue culture for use in standardized assays to study adhesion and migration of rabbit lens epithelial cells in response to type IV collagen, laminin, fibronectin, and ovalbumin. RESULTS: Under these conditions, the adhesion of rabbit lens epithelial cells to surfaces coated with varying concentrations of type IV collagen, laminin, and fibronectin was shown to be dependent on concentration. Rabbit lens epithelial cells did not adhere to ovalbumin-coated surfaces at any concentration tested. Type IV collagen promotes maximal in vitro adhesion of rabbit lens epithelial cells at lower coating concentrations in comparison to laminin and fibronectin. In cell migration experiments, fibronectin promoted maximal migration at lower concentrations in comparison with laminin and type IV collagen. This was shown both in haptotaxis experiments (the migration of cells to surfaces coated with protein) and in chemotaxis experiments (the migration of cells to attractants in solution). Lens epithelial cells did not migrate in response to ovalbumin under the conditions of this study. CONCLUSION: The results of these studies indicate that adhesion and migration of lens epithelial cells occurs in response to the lens capsule proteins type IV collagen and laminin and in response to fibronectin, a protein found in the lens during embryologic development. Because fibronectin plays a role in the embryologic development of the lens but is not normally present in the adult lens, the possible introduction of fibronectin into the eye after surgery may play a critical role in the posterior migration of lens epithelial cells and the development of posterior capsular opacification or secondary cataract. PMID- 8360017 TI - Calcium regulation in tissue-cultured human and bovine lens epithelial cells. AB - PURPOSE: To study calcium regulatory mechanisms in lens cells with particular reference to the relative contributions from the calcium adenosine triphosphatase of plasma and endoplasmic reticulum membranes, respectively. METHODS: The calcium sensitive fluorescent dye, Fura 2, was incorporated into tissue-cultured human and bovine epithelial cells and internal calcium was calibrated using the ionomycin (1 microM) method. The dynamics of calcium release from the endoplasmic reticulum were also studied in digitonin-permeabilized bovine cells. RESULTS: Tissue-cultured bovine and human lens cells have very similar resting calcium levels (235 +/- 22 nM and 216 +/- 12 nM, respectively). Thapsigargin caused an increase in cytoplasmic calcium both in the presence and absence of external calcium, but the calmodulin antagonist W7 only initiated an increase in the presence of external Ca2+. The effects of thapsigargin and W7 were additive. Exposing lens cells to Na(+)-free perfusing solutions caused a transient increase in internal Ca2+. Bovine lens cells permeabilized by digitonin-released Ca2+ when exposed to inositol (1,4,5) triphosphate and the effect was maximal at 1 microM. CONCLUSIONS: Lens cytoplasmic calcium is controlled by calcium adenosine triphosphatases at the plasma and endoplasmic reticulum membranes. The former is inhibited by W7 and insensitive to thapsigargin whereas the latter is inhibited by thapsigargin, but insensitive to W7. The lens endoplasmic reticulum store is also controlled by an inositol (1,4,5) trisphosphate calcium-release mechanism. Na+/Ca2+ exchange plays a relatively minor role in calcium regulation, at least at resting calcium levels. PMID- 8360018 TI - Enzyme activities in human lens epithelium of age-related cataract. AB - PURPOSE: To investigate associations between enzyme activity of glutathione reductase (GR) with and without added flavin adenine dinucleotide (FAD), glutathione peroxidase (GPX), and 6-phosphogluconic dehydrogenase (6PGDH) in the lens epithelium collected at surgery, and some nutritional and biochemical variables determined in the same individuals during the Italian-American Case Control Study of age-related cataract. METHODS: One hundred eighty-three epithelium capsule samples were collected from 174 patients undergoing surgery. Data on enzyme activity were obtained from 52 samples for 6-PGDH and from 53 samples for GR and for GPX. The Lens Opacity Classification System II was used to classify and grade cataracts. RESULTS: No correlation was found between enzyme activity in lens epithelium and the same enzymatic activity in erythrocytes (with the exception of a negative correlation between lens and erythrocyte 6PGDH activity), or the type and severity of cataract. No correlation was found between lens GPX activity and plasma selenium and between lens GR activation coefficient (GRAC) and riboflavin intake. Lens GR with added FAD and lens GRAC were significantly correlated to plasma vitamin E level. Lens GRAC was positively correlated to a nutritional vitamin index. CONCLUSIONS: Present data stress the difficulty in verifying the assumption that biochemical indices collected on plasma and on erythrocyte actually reflect the status of these factors in the lens itself. PMID- 8360019 TI - Effects of oxygen and carbon dioxide on human retinal circulation. AB - PURPOSE: Carbogen, a gas mixture of 95% O2 and 5% CO2, is given to patients with retinal artery obstruction in an attempt to improve retinal oxygenation. The purpose of this study was to compare the effects of carbogen and 100% O2 breathing on retinal blood flow. METHODS: On two separate occasions, 12 normal, healthy volunteers breathed air and then either 100% O2 or carbogen while laser Doppler velocimetry measurements and monochromatic fundus photographs were taken. Retinal vessel diameter, maximum velocity of red blood cells, and volumetric blood flow rate were determined in a main temporal vein. RESULTS: Both 100% O2 and carbogen caused significant average reductions in vessel diameter (14.1% and 10.6%, respectively), maximum red blood cell velocity (42.1% and 27.3%, respectively), and blood flow (56.4% and 42.2%, respectively). The average vasoconstriction of the large retinal veins caused by carbogen was not significantly smaller than that caused by 100% O2. The average reductions in maximum red blood cell velocity and blood flow caused by carbogen were significantly smaller than those caused by 100% O2 (P < .001 and P < .01, respectively). CONCLUSIONS: In normal subjects, inhalation of carbogen leads to less reduction in blood flow than inhalation of 100% O2, presumably by reducing the vasoconstriction of small arterioles induced by elevated oxygen levels. PMID- 8360020 TI - An elevated hematogenous photosensitizer in the preterm neonate. AB - PURPOSE: Human blood contains low levels of protoporphyrin IX (PP IX), a photoactive compound that produces reactive oxygen species when exposed to light. It has been proposed that photoactivation of PP IX and subsequent generation of potentially tissue-damaging reactive oxygen may be a mechanism of retinal injury in retinopathy of prematurity (ROP). The purpose of this study is to determine an association between blood PP IX level and infant birth-weight and gestational age. METHODS: Erythrocyte PP IX levels were measured from the umbilical cord blood of 31 neonates, both full term and preterm. Birthweights and gestational ages were recorded. RESULTS: PP IX levels in infants weighing < 1000 grams (n = 7) average 200 micrograms/dl, which is significantly higher than PP IX levels in infants weighing > 1000 grams (125 micrograms/dl, n = 24; P < 0.02). CONCLUSION: Elevated PP IX levels may place preterm neonates at increased risk for photosensitizing retinal injury. PMID- 8360021 TI - Retinal vessel circulation patterns visualized from a sequence of computer aligned angiograms. AB - PURPOSE: To present a computer method that can be used to combine the images from a sequence of fluorescein angiograms of the retinal microcirculation so that a composite image can be generated and a color image illustrating circulation at all points in the vascular network can be computed. This should enable more accurate comparison of retinal vascular occlusions that occur during cardiopulmonary bypass surgery. METHODS: Photographic negatives of the macular region from two angiographic sequences, one taken before surgery and the other taken just before the end of bypass, were digitized, background shade corrected, and registered. Composite images were generated as minimum projection images and the filling images generated from parameters of a smooth curve fit to the filling data at every point. RESULTS: The composite images showed a filling pattern that more accurately reflected the maximum fluorescence at every point than any single image. The images generated from the filling data provide a new way to visualize and quantify changes in the retinal circulation. CONCLUSIONS: The technique demonstrates that problems arising from selection of a single frame from a filling sequence can be overcome by combining images. The technique used to generate the color-coded filling image should prove useful for any image sequence in which differential filling is of interest. PMID- 8360022 TI - Immunologic cross-reactivity in the pathogenesis of ocular onchocerciasis. AB - PURPOSE: Onchocerca volvulus, a filarial worm, is a major cause of infectious blindness and inflammatory eye disease. An autoimmune cause for ocular onchocerciasis has been suggested since the identification of a recombinant antigen of O. volvulus that shows immunologic cross-reactivity with a host ocular component of 44,000 M(r). The aim of this study was to establish the distribution of the cross-reactive antigens in both host tissues and the parasite, and to determine if significant autoantibody responses to the host antigen could be detected in infected persons. METHODS: The tissue and organ distribution of the 44,000 M(r) antigen was determined by immunocytochemistry and Western blot analysis. Human autoantibody responses to the ocular antigen were demonstrated by Western blot analysis using sera collected from persons with onchocerciasis, with and without posterior segment pathology, Bancroftian filariasis, and Europeans with no filarial infection. RESULTS: The tissue distribution of the 44,000 M(r) antigen correlates with the sites of pathology in onchocerciasis and antibody reactivity against this antigen could be detected in all persons with onchocerciasis and posterior segment pathology. The antigen is also recognized by sera from persons with Bancroftian filariasis, but not from normal persons. CONCLUSIONS: A role is proposed for immunologic cross-reactivity in the pathogenesis of onchocerciasis and it is suggested that intraocular presentation of the cross-reactive parasite antigen by microfilariae is essential for the development of disease. PMID- 8360023 TI - The paradoxical effect of tumor necrosis factor alpha (TNF-alpha) in endotoxin induced uveitis. AB - PURPOSE: To investigate the role of TNF-alpha in endotoxin-induced uveitis (EIU) in mice. METHODS: To neutralize TNF-alpha activity, mice were pretreated with either repeated injections of this cytokine or a single injection of antibody against it. The mice were then injected intraperitoneally with 500 micrograms endotoxin, to induce lethal septic shock, or into the footpad with 200 micrograms to induce EIU. RESULTS: Although both pretreatments conferred protection against the systemic toxic effects of LPS, TNF-resistant mice and mice treated with anti TNF-alpha antibody demonstrated an exacerbation of EIU when compared to control animals. CONCLUSIONS: Unlike its apparent participation in the systemic effect of endotoxin, TNF-alpha is not directly involved in the pathogenesis of EIU and may even protect against the inflammatory processes of this disease. PMID- 8360024 TI - Rods and cones contain antigenically distinctive S-antigens. AB - PURPOSE: S-antigen (48 kDa protein or arrestin) is known to be present in rod photoreceptors. Its localization in cones is less clear with several conflicting reports among various species examined. METHODS: This study employed three different anti-S-antigen antibodies (a48K, a polyclonal antiserum and two monoclonal antibodies, MAb A9-C6 and MAb 5c6.47) and examined their localization in rods and cones of human and cat retinas. To identify the respective cone types, an enzyme histochemical technique for carbonic anhydrase (CA) was employed to distinguish blue cones (CA-negative) from red or green cones (CA-positive). S antigen localization was then examined by immunocytochemical staining of adjacent sections. RESULTS: In human retinas, a similar labeling pattern was seen with both a48K and MAb A9-C6, i.e., the rods and blue-sensitive cones were strongly positive, whereas the red- or green-sensitive cones showed little immunoreactivity. All human photoreceptors showed reactivity to MAb 5c6.47. In the cat retina, only CA-positive cones could be found. As in the human retina, both rods and cones of the cat were positive for MAb 5c6.47. A difference from the labeling pattern in human retina was noted for the other S-antigen antibodies; a48K labeled rods and all of the cones, whereas MAb A9-C6 reacted strongly with the rods but showed no cone staining. CONCLUSIONS: These results suggest that both rods and cones contain S-antigen but that they are antigenically distinctive. PMID- 8360025 TI - Anterior chamber-associated immune deviation elicited via primate eyes. AB - PURPOSE: To determine whether injection of a soluble antigen, ovalbumin (OVA), into the anterior chamber of cynomolgus monkey eyes would impair the ability of these animals to subsequently develop delayed hypersensitivity when confronted by this antigen in immunogenic form. METHODS: OVA or phosphate-buffered saline was injected into the anterior chamber of adult cynomolgus monkeys that were subsequently immunized with OVA in adjuvant and then skin challenged for delayed hypersensitivity with OVA. RESULTS: Recipients of intracameral OVA proved unable to acquire antigen-specific delayed hypersensitivity when they received an immunogenic regimen of OVA in adjuvant. Since the flow of aqueous humor through the uveoscleral pathway of primate eyes can be promoted by topical treatment with PGF2 alpha isopropylester, a preliminary experiment is described in which induction of anterior chamber-associated immune deviation by OVA was prevented when the antigen was first introduced into monkey eyes treated with PGF2 alpha isopropylester. CONCLUSIONS: Monkeys resemble rodents in displaying anterior chamber associated immune deviation (impaired ability to acquire antigen-specific delayed hypersensitivity) when they first encounter an antigen via the anterior chamber. The findings suggest that the cellular and molecular mechanisms of immune privilege, recently described in rodents, may apply to immune responses to intraocular antigens and pathogens in primates, including humans. Primate eyes offer an opportunity to explore the mechanisms of anterior chamber-associated immune deviation using pharmacologic agents that modify the aqueous outflow tracts. PMID- 8360026 TI - Quantitative analysis of iris translucency in Fuchs' heterochromic cyclitis. AB - PURPOSE: To measure intraocular stray light and to quantify translucency of the iris and the surrounding ocular wall in both eyes of patients with Fuchs' heterochromic cyclitis; to investigate whether differences in paired eyes could be measured in patients without heterochromia or with a minimal degree of iris atrophy. METHODS: Intraocular stray light was measured by means of the direct compensation technique. A modification of this technique was used to quantify translucency of the iris and the surrounding ocular wall. RESULTS: Intraocular stray light proved to be significantly higher in all patients with Fuchs' heterochromic cyclitis (both eyes) than in normal control subjects. Translucency of the iris and the ocular wall around it were increased in the patients with Fuchs' heterochromic cyclitis, including patients without heterochromia or with a minimal degree of iris atrophy. CONCLUSIONS: Quantitative analysis of translucency was used to determine iris depigmentation in vivo in patients with Fuchs' heterochromic cyclitis. This technique showed that the process of atrophy and depigmentation in patients with Fuchs' heterochromic cyclitis is probably not restricted to the iris, but also occurs in the surrounding ocular wall. More studies, including other uveitis groups, are necessary to investigate if this technique can be used as a diagnostic tool in Fuchs' heterochromic cyclitis. PMID- 8360027 TI - Nuclear muscarinic acetylcholine receptors in corneal cells from rabbit. AB - PURPOSE: Previous studies have indicated that muscarinic acetylcholine receptors (mAChR) may be present in an unexpected, unique location and play a singular role in cellular growth regulation of rabbit corneal epithelium that may be of general physiologic significance if found in other cells. The purpose of this study was to examine rabbit corneas and corneal cells in culture to determine mAChR location and tissue distribution. METHODS: Using [3H]-propylbenzilylcholine mustard ([3H]PrBChM), which binds covalently to the active site of mAChR, rabbit corneal cross-sections, cultured corneal keratocytes, epithelial and endothelial cells, as well as nuclei isolated from these cultured corneal cells were labeled, stained, and autoradiographed. Nuclei labeled with [3H]PrBChM were further analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: Direct visual confirmation of the localization of mAChRs was obtained. MAChR were found in epithelial and endothelial layers of fresh-frozen corneal cross sections, in cultured rabbit epithelial and endothelial cells, and on isolated rabbit epithelial and endothelial cell nuclei. mAChR were not detectable in keratocytes with these techniques. When [3H]PrBChM-labeled nuclei from cultured corneal cells were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, epithelial and endothelial samples showed specific mAChR binding, whereas binding to keratocyte nuclei was not detectable. CONCLUSIONS: As a result of these findings, a revised hypothesis is suggested for the locations and possible functions of mAChR in regulation of growth in corneal and other cells. PMID- 8360028 TI - Interlamellar cohesive strength in the vertical meridian of human eye bank corneas. AB - PURPOSE: Previously, human corneal stromal interlamellar cohesive strength in the horizontal meridian was shown to be twice as strong peripherally as centrally (approximately 2.90 x 10(-1) versus 1.40 x 10(-1) N/mm). In the current study, stromal samples excised from the vertical meridian were studied to determine if meridional differences also exist. Precise knowledge about corneal stromal structure is warranted, because anisotropy can influence postoperative healing strength and corneal shape. METHODS: Limbus-to-limbus stromal strips with a constant 2.2-mm width were obtained from the vertical meridians of 52 eyebank corneas (8 single, 22 pairs). Cohesive strength was recorded as samples were split at a constant 1.6 mm/s at 50% stromal depth. RESULTS: The mean cohesive strength in the inferior periphery was found to be only two thirds the strength observed in the nasal or temporal periphery (1.96 x 10(-1) N/mm versus approximately 2.94 x 10(-1) N/mm @ 5 mm). The mean cohesive strength in the inferior periphery was also significantly less than the strength of the superior periphery (1.85 x 10(-1) N/mm +/- 8.83 x 10(-3) SEM versus 2.34 x 10(-1) +/- 1.37 x 10(-2) @ 4 mm from the central cornea; P = 0.0027). Unlike the samples from the horizontal meridian, which could be described by a profile symmetric about the central cornea, force profiles for the vertical data could be characterized with distinct, classifiable patterns that were generally asymmetric. Fellow corneas from a single donor tended to have strength profiles belonging to the same class (P = 0.035; chi-square), although some paired eyes exhibited profiles from distinctly different classes. CONCLUSIONS: These data strongly support the concept of an anisotropic collagen macrostructure that is more complex than previously believed. This inherent structural anisotropy may become a significant determinant of corneal shape during ectatic disease and some forms of keratorefractive surgery. PMID- 8360029 TI - Egocenter location in children with strabismus: in the median plane and unchanged by surgery. AB - PURPOSE: Previous studies have shown that there are spatial localization shifts after horizontal strabismus surgery when a patient performs an open-loop pointing task. After monocular enucleation, an adult will also show a shift in the pointing response. Other studies have shown that in children who underwent enucleation, the egocenter location shifts toward the remaining eye. Is the pointing shift after surgery in children with strabismus the result of a shift in egocenter location? METHODS: Using a modified Roelofs' method for measuring the egocenter, eight children were tested before and after horizontal strabismus surgery to see if there were any shifts in egocenter location. One control group consisted of six children undergoing surgery for correction of vertical strabismus in which the horizontal muscles would be unaltered. RESULTS: Presurgery measurements of egocenter location in the people with strabismus were the same as those found in the other control group of 12 normal children. Postsurgical measurements of eye position showed horizontal rotations of 14.5 degrees for the horizontal group and 2.4 degrees for the vertical group. Egocenter measurements showed no postoperative shift for either strabismus group. CONCLUSIONS: Thus, the pointing shift seen in the previous studies is not from a shifting egocenter location but from a change in the registered position of the eye in the orbit. PMID- 8360030 TI - Objective concurrent measures of open-loop accommodation and vergence under photopic conditions. AB - PURPOSE: To investigate the relationship between photopic open-loop accommodation and vergence and the effect of mental effort on these positions. METHODS: Twenty subjects (11 men and 9 women) viewed monocularly a photopic (25 cdm-2), high contrast (90%) Maltese cross-target for 3 minutes, through a 0.5-mm pinhole drilled into an infrared filter. Accommodation was measured objectively at 1 second intervals using a Canon Autoref R-1 infrared optometer, and vergence was recorded continuously and objectively using a differential infrared eye tracking system. RESULTS: Under passive viewing conditions there was a significant correlation between photopic open-loop accommodation and vergence (R = 0.671, P = 0.0012); for the majority of subjects the imposition of mental effort shifted the passive levels of both open-loop accommodation and vergence, but these shifts were unsystematic and uncorrelated (R = 0.259, P = 0.270). The active open-loop positions of accommodation and vergence were also found to be correlated (R = 0.692, P = 0.0007). CONCLUSIONS: The influence of proximal stimuli can explain the correlations identified between photopic open-loop positions of accommodation and vergence. The uncorrelated responses of the accommodation and vergence systems to mental effort are likely to reflect interactions between various spatiotopic stimuli including mental effort and perceived proximity. PMID- 8360031 TI - Visual stabilization of posture in retinitis pigmentosa and in artificially restricted visual fields. AB - PURPOSE: To investigate the relationship between retinitis pigmentosa (RP) progression and the visual contribution to posture stabilization; to examine the extent to which visual-field diameter affects the visual contribution to posture stabilization. METHODS: Posture information was recorded in 35 subjects with well characterized RP and in 20 subjects with normal vision. Data were collected as each subject stood in a dark environment and as each subject viewed a stationary visual display. In both conditions, somatosensory feedback was concurrently altered. Data were also collected on 10 additional subjects with normal vision wearing field-restricting goggles (visual-field diameters ranged from 26.5 down to 6 degrees). RESULTS: RP progression is accompanied by a steady decrease of the visual stabilization of posture, from normal values at the onset of the disease to the absence of visual stabilization and, eventually, to visual destabilization of posture. Decreasing visual field diameter in the subject with normal vision resulted in a linear decrease of the visual stabilization of posture. However, subjects with RP with comparable visual-field loss showed significantly lower visual stabilization than normal subjects with artificially restricted fields. Moreover, subjects with normal vision with restricted visual fields as small as 6 degrees failed to show visual destabilization of posture. CONCLUSIONS: Most likely, the additional reduction in the visual stabilization of posture shown in subjects with RP, as well as the visual destabilizing effect manifest in the late stages of RP, is caused by anomalous processing of visual information in the remaining visual field. PMID- 8360032 TI - Mechanisms mediating visual detection in static perimetry. AB - PURPOSE: The usual stimuli in static perimetry are white-light luminance increments. However, the specific visual detection mechanisms involved in perimetry are unknown because all classes of neural mechanisms are sensitive to spectrally broadband stimuli. The objective of this study was to determine the relative sensitivities of nonopponent and opponent detecting mechanisms under standard perimetry test conditions. METHODS: Using trained rhesus monkey subjects, the relative sensitivities of the vision mechanisms for the detection of perimetry test stimuli were determined through psychophysical measurements of spectral sensitivity at each of the test field locations of the C24-2 threshold program on the Humphrey Field Analyzer (Allergan Humphrey, San Leandro, CA). The spectral sensitivity functions were analyzed by a three-channel model that incorporated independent short-wavelength-sensitive, nonopponent (luminance), and opponent (chromatic) spectral sensitivity mechanisms. RESULTS: The visual detection mechanisms for perimetry thresholds varied as a function of the size and wavelength of the test field. With the perimeter's standard stimulus (Goldmann Size III) and bowl illumination (31.5 asb), the presence of a short wavelength-sensitive mechanism was clearly evident at all field locations, but its relative sensitivity systematically declined with eccentricity. Under these conditions, the sensitivities of the opponent and nonopponent mechanisms were approximately equal at most field locations. With a larger stimulus (Goldmann Size V), however, the contribution of the opponent spectral sensitivity mechanism was more apparent over most of the central field and the alterations of sensitivity with eccentricity were less pronounced. In contrast, a small test field (Goldmann Size II) appeared to bias detection toward nonopponent mechanisms. CONCLUSION: The results of these investigations indicate that detection thresholds during perimetry can be effectively biased toward different photopic, visual processing channels through the appropriate selection of size and wavelength of the test stimulus. PMID- 8360033 TI - Migraine headache and its association with open-angle glaucoma: the Beaver Dam Eye Study. AB - PURPOSE: To investigate the relationship of a history of migraine headache to open-angle glaucoma. METHODS: In an epidemiologic study of age-related eye disease, subjects were asked if they had migraine headaches. The diagnosis of glaucoma was based on visual field, intraocular pressure, cup/disc ratio, and history. RESULTS: Those younger than 65 years were significantly more likely to report a history of migraine (P = 0.001) as were women (P < 0.001). There was no difference in the frequency of open-angle glaucoma between those with and those without migraine headache (P = 0.87). Multivariate analyses did not alter the conclusion. CONCLUSION: In this population-based study there is no evidence of a relationship between open-angle glaucoma and migraine headache. PMID- 8360034 TI - Chronic desquamative gingivitis. PMID- 8360035 TI - Advertising for professional services: what the rules say. PMID- 8360036 TI - Management of respiratory infections in the elderly. PMID- 8360037 TI - Medical management of ulcerative colitis. PMID- 8360038 TI - The management of gastric ulcers in general practice. PMID- 8360039 TI - Ankylosing spondylitis. A comparison of clinical and radiographic features in men and women. AB - The clinical and radiographic features of 83 patients with a diagnosis of Ankylosing Spondylitis conforming to Rome criteria were reviewed. There was 64 males and 19 females attending for a mean duration of 13 and 11 years. Females presented with more peripheral arthritis (X2 = 3.15464, DF = 1, P < .05 (one sided) and more asymptomatic sacroiliitis (X2 = 6.70172; DF = 1, P < .01 (two sided)). Spinal involvement occurred with a similar frequency in men and women, no increase in cervical spine involvement in women was identified. Four males and one female of 83 patients, developed radiographically proven spinal fusion. One male patient developed upper lobe pulmonary fibrosis, one male patient developed the cauda equina syndrome, one male patient required a total hip replacement. No statistically significant difference in the rate of complications in men and women was identified. PMID- 8360040 TI - Hospital initiated prescribing in the General Medical Services scheme. AB - Twenty-seven general practitioners associated with the Department of Community Health and General Practice, TCD, agreed to record details of the drugs prescribed on 30 consecutive GMS prescriptions. Doctors were asked to indicate whether the items they were prescribing were initiated by themselves or by a hospital doctor and whether they agreed with the latter items in terms of their clinical appropriateness and cost. Information on 1,471 prescribed items was obtained from a total of 754 prescriptions. General practitioners initiated 63% of these items, hospital doctors 35% and in 2% the person responsible was unknown. Hospital initiated items accounted for 44.5% of total ingredient costs compared with 54% in general practice. General practitioners agreed with most of the hospital initiated items in terms of their clinical appropriateness and cost. Given the extent of hospital initiated GMS prescribing in this study there is a clear need to differentiate between those items originating in hospital and those in general practice for accountability purposes. PMID- 8360041 TI - Alcohol use in post-primary school children. AB - The prevalence of alcohol use of Irish post-primary schoolchildren has been reported on numerous occasions over the past five years. A study of drinking patterns in 294 schoolchildren aged 14 to 17 from single sex and mixed sex schools is presented. The age at first drink for boys was 11.7 years, and for girls 12.3 years. Eighty percent of boys had ever drank compared to 66% of girls. 59% of boys were regular drinkers compared to 54% of girls. Both these parameters were equal for boys from single sex and mixed schools but girls from mixed sex schools had a higher prevalence of drinking than girls from single sex schools. Beer was by far the favourite drink of boys whereas wine was the favourite drink of girls. Girls were more likely to drink at home than boys. The results of the present study will be compared with other recent prevalence studies of teenage alcohol use in Ireland. Many findings are similar but the separate analysis of single and mixed sex schools is new. PMID- 8360042 TI - Sexual behaviour and knowledge of normal children as perceived by their parents. AB - This study set out to examine sexual behaviour and knowledge of normal children as perceived by their parents. The study was carried out in two settings; a) general practice and b) an acute paediatric admission ward. Families where there was a history or suspicion of child abuse or neglect were excluded. The parents (62 mothers and 22 fathers) of 84 children aged three to twelve years, from a variety of social backgrounds, were interviewed. The majority of parents saw mothers as the main and most important source of information on sexual matters for their children. Parents believed that their children were able to talk freely to them about sexual matters, and most had discussed general information about reproductive matters without going into detail with their children. Parents perceived their children as having little interest in the genitalia of others, except during nappy changing or bathing of preschool siblings. Few parents were aware that their children masturbated although many mentioned "nervous fiddling" with genitals by male children. More explicit sexual behaviour among children, such as simulated intercourse, were distinctly unusual. The parents of 14% of boys and 44% of girls were unaware of what word (correct or slang) their child used to describe their own genitalia. The results of this study suggest that explicit sexual activities or preoccupations that come to adult attention are distinctly unusual in normal children. While parents can talk in a general way with their children about reproductive matters, specific details about sexual behaviour tend not to be discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360043 TI - Prevalence of asthma in Galway city school children. AB - To determine the prevalence of asthma in the past 12 months in nine year old Galway school children, a questionnaire on respiratory symptoms was distributed to children for completion by parents and returned to the school. We issued 896 questionnaires and 832 (426 boys and 406 girls) were returned completed. The overall response was 93%. The prevalence of wheeze in the past 12 months was 16.1%. A history of wheeze was more common in boys than in Girls. (19.7% Vs 12.3%). Overall, 67% of those reporting wheeze also reported a history of diagnosed asthma and 74% had used a bronchodilator. 60% reported a history of exercise induced wheezing and 67% had nocturnal cough. 28% were taking prophylactic medication. The current prevalence of asthma in Galway city school children is high. There is an increased willingness to diagnose and treat asthma in this community. PMID- 8360044 TI - Prevalence of hepatitis A IgG in Irish international travellers. AB - The authors have studied the sero-conversion levels of Irish international travellers over the past 6 years with regard to Hepatitis A IgG levels. The rate of sero-conversion is significantly associated with patient age (x2 = 77.8, df = 1, p < 0.0001). There was no significant difference in the antibody levels between males and females. The results show that a large proportion of younger people travelling to developing countries are unprotected against Hepatitis A. Also approximately 30% of travellers over the age of 40 years have not seroconverted from previous exposure and therefore remain at risk. The mortality associated with Hepatitis A is in high risk groups. Therefore vaccination should be considered. PMID- 8360045 TI - Invasive group A streptococcal infections of children. PMID- 8360046 TI - Plantar responses in infancy. PMID- 8360047 TI - Carcinoma of the tonsillar region: a multivariate analysis of 243 patients treated with radical radiotherapy. AB - Between October 1964 and June 1990, 243 patients with squamous cell carcinoma of the tonsillar region were treated with continuous-course radical radiotherapy at the University of Florida. All patients had a minimum 2-year follow-up. Patients were staged according to the AJCC system; stage IV was stratified into two subsets: favorable, IVA (T1-T3 or N2A-N3A); and unfavorable, IVB (T4 or N3B). The initial and ultimate local control rates (including surgical salvage) according to T stage were as follows: T1, 87% and 100%, T2, 79% and 92%; T3, 71% and 76%; and T4, 44% and 48%. Multivariate analysis demonstrated that anterior extension of the primary tumor (p = .0001) and T stage (p = .014) were the most significant parameters affecting local control after radiotherapy. For T4 lesions, twice daily irradiation significantly improved local control (p = .04). The 5-year absolute and cause-specific survival rates as a function of modified AJCC stage were as follows: I, 37% and 100%; II, 55% and 90%; III, 55% and 85%; IVA, 35% and 60%; and IVB, 23% and 38%. The probability of a severe complication was 3% for the entire group of patients. PMID- 8360048 TI - Cartilage-shaving procedure for the control of tracheal cartilage invasion by thyroid carcinoma. AB - This study was carried out to ascertain whether the cartilage-shaving procedure is appropriate to control thyroid carcinoma with tracheal cartilage invasion. Of 432 thyroid carcinoma patients treated between 1979 and 1988, 16 had tracheal cartilage invasion only. This patient population was made up of 3 men and 13 women, with a mean age of 55.8 years. Fourteen were diagnosed histologically as having papillary carcinoma and the remaining two as having follicular carcinoma. Cartilage shaving was the primary treatment in all the patients, and subsequent radioactive iodine (131I) or external-beam radiotherapy was administered to control any possible residual disease. Lifelong thyroid hormone replacement was instituted in all patients, and the follow-up period averaged 70.7 months. Only four of the 16 patients remained disease free; the disease was not controlled in the other 12, and seven of this latter group eventually died of their disease. We feel that a more extensive resection procedure than cartilage shaving should be considered, even in patients with superficial tracheal invasion, to increase the disease-free survival rate. PMID- 8360049 TI - Salvage surgery of cervical recurrences after neck dissection or radiotherapy. AB - A series of 113 patients operated on in the period 1980-1989 for a neck recurrence from a head and neck cancer was studied. All patients had no other evidence of disease. The male/female ratio was 93/20, and the median age was 58 years (range 28-87). Previous treatment consisted of surgery (SG) +/- radiotherapy (RT) in 81 patients (SG group) and only RT in 32 (RT group): 59 cases presented a relapse in the treated neck and 54 in the contralateral side. All but one contralateral recurrences were in the SG group. Ten patients were lost to follow-up. The observed 5-year survival rate of the whole series was 29.2% (95% confidence interval, 0%-38%). Considering patients with ipsilateral recurrences, the 5-year disease-free survival rate was 38.7% (95% c.i., 28.7% 48.7%) and 27% (95% c.i., 18%-36%) for the SG and the RT group, respectively. The 5-year disease-free survival rate after SG for contralateral recurrences was 38.8% (95% c.i., 23.8%-53.8%). Dimension and mobility of the neck nodes were the only demonstrable prognostic factors. PMID- 8360051 TI - Base of tongue carcinoma: patterns of failure and predictors of recurrence after surgery alone. AB - Between January 1971 and December 1986, 55 patients with squamous cell carcinoma of the tongue base underwent complete surgical resection with curative intent. No preoperative or postoperative adjuvant therapy was administered. The study group consisted of 41 men and 14 women (median age 61 years). All patients were followed until death (39 patients) or for a median of 9.4 years. Local control at 5 years was 74%. No predictors of local recurrence were discovered. Control in the dissected neck at 5 years was 68%. Control of cancer above the clavicles at 5 years was 48%. Distant metastases developed in 14% of the patients by 5 years. Cause-specific survival at 5 years was 65%. A Cox multivariate regression analysis revealed that pathologic N stage was the only significant independent predictor of recurrence in the dissected neck, recurrence above the clavicles, and cause-specific survival. The 5-year overall survival was 55%. Surgical mortality was 4%. PMID- 8360050 TI - Pretreatment neck node biopsy, distant metastases, and survival in nasopharyngeal carcinoma. AB - Pretreatment neck node biopsy had been performed on 50 of 422 patients who had cervical node metastases from nasopharyngeal carcinoma when initially seen. Multivariate analysis using the Cox proportional hazards model shows that pretreatment node biopsy is not a significant determinant of distant metastases, survival, or recurrence in the neck. Results of similar studies are reviewed and the role of pretreatment node biopsy in nasopharyngeal carcinoma discussed. PMID- 8360052 TI - Treatment of stage I and II oral tongue cancer. AB - We reviewed 156 previously untreated patients with squamous cell carcinoma of the oral tongue staged T1 and T2 to determine the incidence of nodal metastasis, and if elective neck dissection affected local/regional control or survival. Patients were divided into two nonrandomized groups: group 1, intraoral glossectomy only (102 patients); and group 2, intraoral glossectomy plus neck dissection (54 patients). Analysis revealed no significant differences for tumor location, histologic differentiation, status of margins, or clinical appearance; however, perineural invasion significantly adversely affected survival and local/regional control. In group 1 patients, 16.5% subsequently developed cervical metastasis, and 20.4% of patients in group 2 had occult nodal disease. The survival and local/regional control for group 1 patients subsequently developing nodes was 33% and 50%, respectively. The survival and local/regional control for group 2 patients with occult metastasis was 55% and 91%, respectively. We believe elective neck dissection is indicated for early staged oral tongue cancer. PMID- 8360053 TI - Carcinomas of the lacrimal drainage system. AB - Primary carcinomas of the lacrimal drainage system are rare. These malignant neoplasms typically present as noncompressible, nontender masses with low-grade dacyrocystitis and/or unilateral epiphora. Lymph node metastasis may occur late in the disease course. Complete surgical resection is the best treatment choice; extensive procedures such as orbital exenteration and maxillectomy may be necessary for complete tumor extirpation. Further adjunctive radiotherapy may improve local control. We present two cases of carcinoma of the lacrimal drainage system, including one locally controlled tumor with apparent lymph node metastasis that occurred 21 years after primary treatment. A review of the histopathology and literature concerning carcinomas of the lacrimal drainage system is presented. PMID- 8360054 TI - Radical radiotherapy for T4 carcinoma of the skin of the head and neck: a multivariate analysis. AB - Sixty-seven patients with 68 stage T4 carcinomas of the skin of the head and neck were treated with radical radiotherapy at the University of Florida between October 1964 and November 1989. Thirty-three lesions were previously untreated and 35 were recurrent. Twenty-nine lesions were squamous cell carcinomas, 37 were basal cell carcinomas, and 2 were basosquamous carcinomas. Minimum follow-up was 2 years. The 5-year local control, local control including surgical salvage, and cause-specific survival probabilities were 53%, 74%, and 75%, respectively. Local control rates with radiotherapy alone were poorer in patients with recurrent lesions (41% vs. 67%, p = .07) or bone involvement (40% vs. 62%, p = .08). Results were analyzed by multivariate methods using local control, local control with surgical salvage, and cause-specific survival as endpoints. The parameters analyzed were histology; size of primary lesion; previous treatment (previously untreated vs. recurrent); involvement of bone, nerve, or cartilage; and skeletal muscle invasion. Three important prognostic factors were identified, each predictive of poorer ultimate local control and cause-specific survival rates: (a) bone involvement (p < .01); (b) recurrent lesions (p < .01); and (c) nerve involvement (p < .02). Radiotherapy alone can control advanced carcinomas of the skin of the head and neck, although lesions that have recurred after prior treatment and those with involvement of bone or nerve are associated with a lower likelihood of cure. PMID- 8360057 TI - Dynamic radiographic imaging following total laryngectomy. AB - Cinepharyngoesophograms of the pharynx were obtained in 51 patients after total laryngectomy for squamous cell carcinoma. The radiological findings were correlated with operative reports and follow-up findings in 47 patients. Postoperative anatomic changes were well-demonstrated radiographically. A spectrum of radiographic findings were observed and included narrowing at the superior surgical closure site in 52% and pseudodiverticula in 47% of all patients. Cricopharyngeal prominence was observed in 15%, fistulae in 10%, and pharyngeal pouches in 6% of all cases. Increased retropharyngeal soft tissue thickness was not found to be indicative of tumor recurrence. We conclude that cineradiography is a useful method for demonstrating both functional and structural changes following laryngectomy for carcinoma. PMID- 8360055 TI - Recovery of postoperative swallowing in patients undergoing partial laryngectomy. AB - This study assessed the achievement of postoperative swallowing in patients undergoing partial laryngectomy surgery. Oropharyngeal swallow efficiency was used to predict time to achievement of outcome. Fifty-five patients were followed for up to 1 year in two hemilaryngectomy and four supraglottic laryngectomy groups. Within 10 days of healing, a videofluoroscopic evaluation enabled the measurement of swallowing efficiency. Times to achievement of oral intake, removal of feeding tube, preoperative diet, and normal swallow were analyzed using actuarial curves. Patients with hemilaryngectomies achieved swallowing rehabilitation sooner than patients with nonextended supraglottic laryngectomies (p < .05) who, in turn, achieved swallowing function sooner than did patients undergoing supraglottic laryngectomies with tongue base resection (p < .05). Median time to attainment of preoperative diet in these three groups was 28 days, 91 days, and > 335 days, respectively. Higher early postoperative oropharyngeal swallow efficiency was related to earlier achievement of oral food intake and of preoperative diet (p < .05). Results show that the time course for swallowing rehabilitation covers an extended postoperative period. In some surgical groups, functional swallowing and eating may be achieved within 3 months of surgery while for other types, significant impairment remains up to 9 months postoperatively Early radiographic assessments of swallowing function are useful in predicting the time to swallow recovery. Recovery of swallowing ability may be delayed in patients who have not achieved oral intake before radiotherapy is started. PMID- 8360056 TI - Value of fine-needle aspiration in the diagnosis of Hurthle cell neoplasms. AB - The cytologic and histologic slides on all patients with a diagnosis of Hurthle cell tumor at Mount Sinai Hospital during the last 12 years were reviewed. There were 67 Hurthle cell tumors of which 15 (22%) were malignant. Four carcinomas (27%) occurred in a background of thyroiditis. Forty-three patients with Hurthle cell tumors had undergone preoperative fine-needle aspiration, of which 31 had satisfactory aspirates. For Hurthle cell neoplasia, fine-needle aspiration cytology had a sensitivity of 83.8% (26 of 31) and positive predictive value of 93% (26 of 28), provided that the aspirate was of adequate cellularity. All 3 cases predicted as Hurthle cell carcinoma on the basis of cellular and nuclear atypia were correctly predicted, but 3 carcinomas composed of bland cells were incorrectly predicted as adenomas. We conclude that aspiration cytology can differentiate nonneoplastic from neoplastic Hurthle cell lesions with high accuracy, but that the differentiation between benign and malignant lesions is less reliable. PMID- 8360058 TI - Hurthle cell adenoma arising in a thyroglossal duct cyst. AB - A 18-year-old black woman was initially seen with a 1-year history of a slowly enlarging midline neck mass. On physical examination this was consistent with a thyroglossal duct cyst. Histologic examination following a Sistrunk procedure revealed a Hurthle cell adenoma arising in a thyroglossal duct cyst. This is the second reported case of a Hurthle cell adenoma arising in a thyroglossal duct cyst. Neoplasms of thyroglossal duct cysts are reviewed. PMID- 8360059 TI - Seven-year follow-up of vanishing bone disease in a 14-year-old girl. AB - A review of the literature revealed 91 cases of massive osteolysis since the first report by Jackson in 1838, including 31 in the maxillofacial region meeting the Heffez criteria. In seven cases, early irradiation was performed, after which no further progression of bone lysis was observed. The young female patient reported here has been followed up clinically and radiologically for 7 years after radiotherapy, during which time she has remained stable, with no progression of the osteolysis. Our experience with this patient appears to confirm that early radiotherapy with a dose of 30-40 Gy prevents further progression of the disease and can even lead to recalcification. On this basis, and provided the patient remains symptom-free, reconstructive surgery appears a viable treatment option. PMID- 8360060 TI - Metastatic thyroid cancer. PMID- 8360061 TI - Answering critical care nursing questions by interfacing nursing research training, career development, and research with biologic and molecular science. AB - Critical care nursing practice encompasses physiologic as well as psychosocial responses of individuals to acute and chronic health care problems. Before solving integrative nursing problems, pathophysiologic information based on state of-the-science biotechnology is needed. More critical care nurse researchers need to answer clinical questions with biologic and molecular science information, measurements, and techniques. The purpose of this article is to describe research training, career development, and research opportunities to facilitate the interface of critical care nursing research with the biologic and molecular sciences. PMID- 8360062 TI - Depression in patients with COPD. AB - Patients with chronic obstructive pulmonary disease (COPD) can have an accompanying depression that interferes with nursing management and reduces patients' quality of life. Nurses need to understand more about that depression, how depression can be manifested and measured in older adults, and how depression in those with COPD differs from that seen in other chronic diseases. Self-report questionnaires can be used to identify depression initially and determine the need for further assessment. The DSM III-R criteria is recommended for those who wish to use a clinical evaluation tool. Treatment for the depression seen in COPD can include pharmacologic therapy and life changes, as well as individual and family therapies. PMID- 8360064 TI - Left bundle branch block-type conduction due to acceleration-dependent aberrancy. PMID- 8360063 TI - Alternatives for cardiac rehabilitation patients unable to return to a hospital based program. AB - OBJECTIVE: To determine the effectiveness of a home exercise program using transtelephonic exercise monitoring (TEM). DESIGN: Prospective, two-group experimental, random assignment. SETTING: Urban centered hospital and surrounding community. SUBJECTS: Twenty cardiac rehabilitation patients entering a Phase II cardiac rehabilitation program. OUTCOME MEASURES: Maximal oxygen consumption, blood pressure, pressure-rate product, workload. INTERVENTION: Twenty male cardiac patients were randomly enrolled in either a 12-week home- or hospital based exercise program. Maximal exercise tolerance tests were conducted, before and after exercise intervention, on a computer-driven bicycle ergometer. Subjects trained 3 days per week for 12 weeks on a bicycle ergometer for a maximum of 35 minutes at 75% of maximum heart rate reserve or functional capacity. RESULTS: Posttraining results showed significant improvement in cardiac function for both groups. Two patients in the TEM group developed new arrhythmias while exercising that required medication changes; however, no medical emergencies arose in either exercise group. Independent Student t test showed no significant difference between groups before or after training. CONCLUSIONS: We conclude that TEM is an effective alternative for the rehabilitation of patients who are unable to return to a hospital-based program. PMID- 8360065 TI - A comparison of the recovery period for women and men after an acute myocardial infarction. AB - OBJECTIVES: To compare return to work, participation in cardiac rehabilitation, and sexual activity in women and men recovering from acute myocardial infarction (AMI). DESIGN: A descriptive survey design was used. Descriptive statistics and chi square analysis were used to compare differences between women and men after an AMI. SETTING: The survey was mailed to the subject's home. SUBJECTS: A purposive sample of 20 women and 42 men. RESULTS: Comparing women with men, there were significant differences in the following activities with women evidencing higher percentages in responsibility for household duties before AMI, and cooking, washing dishes, reading, bed making, laundry, dusting and sweeping within 4 weeks after AMI. For those subjects who were sexually active before AMI, all resumed sexual activities after an average of 8 weeks. Women reported a decrease in frequency, less satisfactory relationship, and more reports of chest pain during sexual activity. Subjects reported that nurses gave little or no counseling concerning resumption of household activities, return to work issues, and sexual activity. Women received less counseling than men after AMI. CONCLUSIONS: The findings are not generalizable to the population at large; however, the study indicates a need to investigate further the recovery period for women who experience AMI. PMID- 8360066 TI - A pilot study of pain, analgesia use, and pulmonary function after colectomy with or without a preoperative bolus of epidural morphine. AB - OBJECTIVE: To determine whether patients who received a preoperative bolus of epidural morphine plus postoperative parenteral analgesia had less pain and better pulmonary function over the first 2 days after a colectomy than patients who received postoperative parenteral analgesia alone. DESIGN: Repeated measures, quasi-experimental, random assignment. SETTING: Northeastern general hospital. SUBJECTS: Thirteen patients were randomized to receive parenteral with (n = 6) or without (n = 7) epidural analgesia. OUTCOME MEASURES: Indicators of pain (intensity of pain and pain-related distress, intensity of words used to describe pain, intramuscular-equivalent amount of morphine administered, duration from start of surgery to first request for analgesia) and pulmonary function (forced expiratory volume in one second FEV1], forced vital capacity [FVC], inspiratory capacity [IC], peripheral oxygen saturation [SaO2] values). MEASUREMENT: Indicators of pain and pulmonary function were obtained the day before surgery, approximately 6 hours after surgery, and the first two mornings after surgery. RESULTS: Six hours after surgery, patients in the epidural group had less pain (p = 0.0177) and related distress (p = 0.0303) and greater FVC (p = 0.0303) and FEV1 (p = 0.0025) than patients in the no-epidural group. On the first postoperative morning, patients in the epidural group had less distress related to pain (p = 0.0350) but similar respiratory rates and spirometry values. Inspiratory capacity was not statistically different but was always larger in the epidural group. Of patients who breathed room air, SaO2 was higher in the epidural group over the first two postoperative days (p = 0.0286 each occasion). Patients in the epidural group received their first on-demand analgesic an average of 30 hours after the start of surgery compared with 6 hours for patients in the no-epidural group (p = 0.0022). There were no significant differences in the total number of words used to describe the type of pain, and both groups described the pain with fewer words than expected on the first and second mornings after surgery. CONCLUSIONS: Results should be confirmed through study of a larger sample with the hypothesis that pain relief, selected aspects of pulmonary function, and peripheral oxygenation may be superior for patients who receive a preoperative bolus of epidural analgesia for abdominal surgery. PMID- 8360067 TI - Oxygen transport variables in the identification and treatment of tissue hypoxia. AB - Critically ill patients have greater than normal oxygen demands because of enhanced energy requirements placed on them by the stress of acute illness, blood and fluid loss, surgery, wound healing, and hospitalization. Early recognition of major alterations in oxygen transport variables, oxygen delivery, oxygen consumption, and the oxygen extraction ratio, by the critical care team assists in the prevention and treatment of tissue hypoxia in seriously ill and injured patients. Supranormal levels of oxygen delivery are required to meet these increased oxygen demands, to prevent tissue hypoxia, and to correct tissue oxygen debt. The critical care team should promptly determine the patient's oxygen transport variables on admission to the intensive care unit to provide a starting point for patient resuscitation. When deviations from supranormal values of oxygen transport variables in these patients are identified, specific interventions that improve oxygen delivery to peripheral tissues should be implemented and evaluated for their effectiveness in normalizing the oxygen extraction ratio. When serial measurements of oxygen delivery, oxygen consumption, and the oxygen extraction ratio follow each therapeutic intervention that is directed at increasing oxygen delivery, the survival rate of critically ill patients is significantly improved. PMID- 8360068 TI - Comparison of two methods of measuring gastric pH. AB - OBJECTIVE: To assess the agreement between two methods of measuring gastric pH in critically ill patients (multiple band litmus paper-tested aspirations versus a meter-read probe located in the tip of a nasogastric tube) and to compare nurse satisfaction with both methods of measuring pH. DESIGN: Prospective, correlational, nonprobability sample. SETTING: Mid-Atlantic, semirural Veterans Affairs Medical Center. SUBJECTS: 39 male, surgical, critical care patients, who were nasogastrically intubated in the operating room and received nothing by mouth. NURSES: Twenty-seven registered nurses on the medical-surgical intensive care staff. OUTCOME MEASURES: Differences in pH units as determined by two methods of measurement and nurse satisfaction scores. INSTRUMENTATION: Litmus paper-tested aspirations versus a meter-read probe located in the tip of the nasogastric tube, measured every 2 hours for 48 hours. A nurse satisfaction assessment form for both measurement methods at entry, 6 months, and 12 months. RESULTS: All measures of association, Pearson's r (0.79), the concordance coefficient (0.74), and eta (0.88), were high. The concordance coefficient measures indicated sufficient agreement between the two methods at the initial and 24 hour measurement times (Cb) = 0.97, 0.97, and 0.94), but not at 48 hours. The meter method indicated prophylaxis was needed when the paper did not, more often than did the paper method (9.3% vs 5.2%). A significant difference between methods was found only at the last reading at 48 hours (z = -2.24, p < .0249). MANOVA revealed that nurses' preference for the meter method was significant (F = 139.48, df = 1.18) and increased over time (F = 4.77, df = 2,36). CONCLUSIONS: The gastric probe method of measuring pH is an accurate substitution up to 48 hours for the litmus-paper aspiration method in the postoperative patient who is receiving nothing by mouth. Nurses prefer the gastric probe method of measuring pH over the litmus-paper method because they judge it to be safer, faster, and more accurate. PMID- 8360069 TI - Emergency department patients' perception of nurse caring behaviors. AB - OBJECTIVE: To identify which behaviors performed by emergency department nurses were perceived by patients as important indicators of caring. DESIGN: Descriptive. SETTING: Two private urban emergency departments. SUBJECTS: Ambulatory patients treated in the emergency department and interviewed by telephone within 30 days of discharge. The resulting sample consisted of a total of 288 interviews including 81 patients in the emergent group, 99 in the urgent group, and 108 in the nonurgent group. Of the 288 patients, 49% were male and 51% were female. OUTCOME MEASURES: Individual and composite measures of perceptions of nurse caring behaviors as measured with the Caring Behaviors Assessment, satisfaction with care, and patients' evaluation of their medical condition. RESULTS: Patients in all triage categories were found to assign the greatest importance to the technical nursing behaviors as indicators of nurse caring. Polychotomous logistic regression indicated that, although subscale differences occurred, they did not account for substantial differences among triage categories. Kruskall-Wallis one way ANOVA revealed no significant differences between triage levels and ratings of level of personal concern. Chi-square analysis indicated that patients in the emergent group identified fewer caring behaviors that the nurse must perform to demonstrate caring compared with patients in the nonurgent group. CONCLUSIONS: Patients experience nurse caring behavior most consistently from the technical aspects of nursing care. PMID- 8360071 TI - Hepatitis. Part I. Enterically transmitted viral hepatitis: etiology, epidemiology, and prevention. PMID- 8360070 TI - Nosocomial tuberculosis in the AIDS era with an emphasis on multidrug-resistant disease. PMID- 8360072 TI - Mycoplasma pneumoniae induced thrombocytopenia. PMID- 8360073 TI - Process of foregoing life-sustaining treatment in a university hospital: an empirical study. (Faber-Langendoen K, Bartels DM. Crit Care Med 1992;20[5]:570 7). PMID- 8360074 TI - Myocardial infarction and cerebral hemorrhage. PMID- 8360075 TI - Chromosomal localization and regulation of the longevity determinant genes in a selected strain of Drosophila melanogaster. AB - A controlled chromosome substitution experiment was performed on a strain (NDC-L) selected for long life to determine if the genes responsible for the extended longevity phenotype could be localized to any particular chromosome(s). All 27 different possible combinations of the three major chromosomes of Drosophila melanogaster were constructed and longevities were determined on 3875 individual animals of both sexes and analysed. The results are statistically significant and demonstrate that mean longevity is specified primarily by recessive genes on the third chromosome (c3). The extended longevity phenotype (ELP) is only expressed in those lines which are homozygous for the NDC-L type c3. Loci on the first (c1) and second (c2) chromosomes interact, both positively (c1) and negatively (c2), respectively, such that c1 represses c2 which in turn represses c3. The ELP is fully expressed in the mutual presence and mutual absence of c1 and c2. The significance of these results is discussed in the context of broader categories of molecular genetic mechanisms suggested previously to be involved in the modulation of longevity in Drosophila. PMID- 8360076 TI - Larval regulation of adult longevity in a genetically-selected long-lived strain of Drosophila. AB - Our previous work has shown that the major genes involved in the expression of the extended-longevity phenotype are located on the third chromosome. Furthermore, their expression is negatively and positively influenced by chromosomes 2 and 1, respectively. In this report we show that the expression of the extended-longevity phenotype is dependent on the larval environment. A controlled chromosome substitution experiment was carried out using a strain selected for long life (L) and its parent (R) strain. Twenty different combinations of the three major chromosomes were conducted and their longevities were determined under both high (HD) and low (LD) larval density conditions. The extended-longevity phenotype was only expressed under HD conditions. The chromosome interactions were not apparent under LD conditions. Density-shift experiments delineate a critical period for expression of the extended-longevity phenotype, extending from 60 h after egg laying (AEL) to 96 h AEL, during which the developing animal must be exposed to HD conditions if the extended-longevity phenotype is to be expressed. The change from HD to LD conditions is accompanied by statistically significant increases in body weight. The possible role of a dietary restriction phenomenon is examined and the implications of these findings discussed. It is now apparent, however, that the extended-longevity phenotype in Drosophila is a developmental genetic process. PMID- 8360077 TI - Regulatory aspects of esterase 6 activity variation in sibling Drosophila species. AB - Esterase 6 in Drosophila melanogaster, Drosophila simulans and Drosophila mauritiana is produced in several life stages and diverse tissues, but the major pulse of expression is in the sperm ejaculatory duct of adult males. Comparison of EST6 activity levels among several lines of D. melanogaster, D. simulans and D. mauritiana reveals two major quantitative differences among the species. First, newly eclosed females of both D. simulans and D. mauritiana show significantly higher EST6 activity than those of D. melanogaster. Secondly, 5-day old adult D. simulans have significantly higher activities than D. mauritiana in both sexes and significantly higher activity than D. melanogaster in males. The genetic bases of the differences between D. melanogaster and the other species are investigated through germ line transfer of the D. simulans and D. mauritiana Est-6 genes plus 1.2 kb of 5' and 0.2 kb of their 3' flanking sequences into D. melanogaster. The newly eclosed female activities of the transformants resemble those of the two donor species, suggesting that the interspecific differences in this aspect of expression are due to cis-inherited factors contained within the transferred DNA. In contrast, the 5-day adult activity of the D. simulans transgene resembles the recipient species, D. melanogaster, suggesting that the difference between D. simulans and D. melanogaster in this aspect of expression is due to trans-acting factors. We also find that third instar larval activities of the D. simulans transgene and 5-day male activities of the D. mauritiana transgene are lower than those of either parental species, suggesting that not all the promoter elements relevant to these aspects of expression are included in the transferred DNA. PMID- 8360078 TI - Correlation between the individual heterozygosity of parents and their offspring. AB - Specific formulations are derived for the correlation between the heterozygosity of a randomly mating parent and its offspring for a diallelic locus, and for the correlation when multiple loci are considered. The expected correlation is maximal, approaching r = 0.50, when allelic frequencies are highly asymmetric, and it is zero when the allelic frequencies are equal to 0.50. Parent-offspring correlations, up to a maximum of 0.50 for diallelic loci, indicate that levels of heterozygosity can respond to selection. Multilocus allozyme data from limber pine, Pinus flexilis, and from horses of standardbred and thoroughbred breeds are used to demonstrate correlations between a parent and its offspring. The Spearman rank correlation between the heterozygosity of a limber pine and the mean heterozygosity of her offspring is r = 0.45. Correlations in the horses range from r = 0.16 to 0.32. PMID- 8360079 TI - Intracellular localization of parvovirus B19 nucleic acid at the ultrastructural level by in situ hybridization with digoxigenin-labelled probes. AB - Conditions suitable for immunogold detection of digoxigenin-labelled DNA probes hybridized to parvovirus B19-infected erythroid cells embedded in Lowicryl K4M and LR White acrylic resins were established at the electron microscope level. The protocol was initially optimized using a positive control probe for whole human DNA which produced signal over the heterochromatin of all nucleated cells. In cultures harvested 2 days postinfection, B19 nucleic acid was detected mainly within the centrinuclear region of erythroid cells exhibiting characteristic margination of the chromatin. The B19 hybridization signal was largely unaffected by denaturation and was resistant to RNase digestion but sensitive to DNase digestion, indicating that it was mainly single-stranded B19 DNA. Relatively few gold particles were found over crystalline arrays of viral capsids, consistent with the observation that they are composed of mainly 'empty' capsids. B19 nucleic acid was detected in apparent transit from nucleus to cytoplasm through pores in the nuclear membrane. While the sensitivity of this system is limited by the fact that hybridization occurs only at the surface of the section, it is a rapid and specific means of localizing viral nucleic acids with a high degree of resolution. PMID- 8360080 TI - The von Kossa reaction for calcium deposits: silver lactate staining increases sensitivity and reduces background. AB - The classical von Kossa method has been modified: the high silver nitrate concentration in the original was replaced by 0.05% silver lactate with hydroquinone remaining the reducing agent of choice. The present modification stained calcification nodules with a sensitivity comparable to the original von Kossa reaction, but resulted in a reduced background staining in cultured osteoblasts. The method works well also with plastic- or paraffin-embedded tissue sections. PMID- 8360081 TI - Ultrastructural localization of lectin-binding sites in different basement membranes. AB - In the present work we localized binding sites for the lectins WGA, RCA I, con A and SBA at the ultrastructural levels in morphologically different basement membranes. These different basement membranes included (a) thin ones, for example, tubular basement membrane of the mouse kidney which separates epithelial cell layers from mesenchymal cells and glomerular basement membrane which separates epithelial cells from other epithelial cells, (b) thick multilayered ones, for example. Reichert's membrane which is built up during the embryonic development of rodents and as an example of a pathologically thickened basement membrane, the basement membrane of the Engelbreth-Holm-Swarm (EHS) sarcoma. We were able to show that, in contrast to the thick multilayered basement membranes, the thin ones showed a strong positive SBA-binding pattern. Thick basement membranes otherwise revealed very strong labelling with the lectins WGA and RCA I. Our findings lead us to conclude that thin and thick basement membranes differ markedly in the quality and quantity of the carbohydrates which they contain. PMID- 8360083 TI - Steel-jaw leghold trap. PMID- 8360082 TI - Animal research. PMID- 8360084 TI - BST product labels--still FDA's call. PMID- 8360086 TI - Looking in on the pet food industry. PMID- 8360085 TI - Veterinary medical degree enrollment, 1992-1993. PMID- 8360088 TI - Comparison of french-pezzar and Malecot catheters for percutaneously placed gastrostomy tubes in cats. AB - Gastrostomy tubes were placed percutaneously in 28 cats by use of an endoscope. French-pezzar mushroom-tip catheters were used for 14 of the procedures, and Malecot catheters were used for the remainder. Inner flanges were not used in gastrostomy tube placement. The french-pezzar catheters remained in place and functional for 2 weeks in all 14 cats. The Malecot catheters remained in place and functional for 2 weeks in 4 cats. Malecot catheters pulled out in 10 cats, and 2 of these cats died or were euthanatized because of complications. The gastrostomy tubes were removed in 18 cats 2 weeks after placement by applying gentle, steady traction and removing the entire catheter or by cutting the tube flush with the skin and leaving the catheter tip in the cat's stomach. Neither method of removal was associated with problems. PMID- 8360087 TI - Effect of trimethoprim/sulfamethoxazole on thyroid function in dogs with pyoderma. AB - The effect of trimethoprim/sulfamethoxazole (T/SMX, 30 mg/kg, PO, q 12 h for 6 weeks) on thyroid function was evaluated in 21 dogs with pyoderma and normal baseline serum thyroxine concentrations. The population mean serum thyroxine concentration, but not the population mean serum triiodothyronine concentration, was significantly decreased at the end of treatment. After 6 weeks of treatment, the response in 3 dogs to thyrotropin administration was substantially reduced. Radionuclide thyroid imaging of 2 dogs after T/SMX treatment revealed higher-than normal thyroid technetium 99m pertechnetate uptake, suggestive of an interference with iodide metabolism. Use of T/SMX may cause hypothyroidism, and inadequate thyroid function may be incorrectly diagnosed in dogs treated with this antimicrobial. PMID- 8360089 TI - Effects of a high-density intramammary device on mammary glands, production, and reproductive performance in dairy cows. AB - A clinical field trial was undertaken to determine the influence of an intramammary device (IMD) on environmental mastitis and production. On 4 central California dairies, 200 Holstein first-lactation cows were randomly assigned to 2 groups. Cows in the treatment group were fitted with an IMD, and cows in the control group were not. The incidence of clinical mastitis for the 2 groups was determined during the study period. Bacteriologic monitoring at intervals over 2 lactations (lactation 2 and through 60 days of lactation 3) was used to determine the incidence of subclinical infection. In addition, data were collected to determine whether the groups differed in milk production, butterfat production, post-milking and test-day somatic cell counts, and reproductive efficiency. Total milk production and butterfat production over the 2 lactation periods did not vary significantly between the groups. Also, the groups did not differ in calving to-conception interval, duration of lactation, calving interval, and calving-to first service interval. Cows with IMD were significantly less likely to develop clinical mastitis (5% vs 13%) than control cows. The IMD did not appear to affect subclinical infection rates (minor pathogens only) except at day 300 of lactation 2 and at day 10 of lactation 3, when prevalence was greater in the cows with IMD. The minor pathogens were predominately (80%) coagulase-negative staphylococci. It was unusual to have coagulase-negative staphylococci in the same quarter at 2 consecutive samplings, prompting the speculation that during lactation, the duration of coagulase-negative staphylococci infection is short (resolves without intervention).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360090 TI - Comparison of enzyme-labeled immunosorbent assay and particle concentration fluorescence immunoassay with standard serologic methods and bacteriologic culture for detection of Brucella sp-infected cows in herds with brucellosis. AB - Bacteriologic culture of udder secretions and card, rivanol, and complement fixation tests for detection of brucellosis were performed on samples from 828 cows vaccinated with strain 19 in herds with brucellosis. An ELISA and a particle concentration fluorescence immunoassay were performed on sera from 560 and 569 cows, respectively. A field strain of Brucella abortus or strain 19 was isolated from 278 cows. The ELISA and the card test had high sensitivity, but low specificity. Data suggested that there is no advantage to using primary binding assays rather than the simple buffered antigen agglutination procedures to detect cows infected with a field strain of B abortus. PMID- 8360091 TI - Ultrasonographic appearance of ruptured peroneus tertius in a horse. AB - Ultrasonography was a valuable diagnostic tool for examination of a ruptured peroneus tertius in a horse, because it allowed visualization of the extent of the injury and evaluation of healing prior to return of the horse to athletic activity. PMID- 8360093 TI - Hypertrophic osteopathy associated with Mycobacterium fortuitum pneumonia in a dog. AB - Mycobacterium fortuitum was isolated from the lung of a dog that had new periosteal bone formation consistent with hypertrophic osteopathy. Fever, weight loss, and bilateral hind limb lameness were the initial clinical signs. The tarsi were swollen and a pain response was elicited on palpation of the hind limb. Radiography revealed periosteal new bone formation on the metatarsi, femurs, and ischii. Thoracic radiography revealed pulmonary mass lesions in the right middle and left caudal lung lobes. After right middle and left caudal lung lobectomy, M fortuitum was isolated from the excised tissues. Amoxicillin trihydrate/clavulanic acid and amikacin were administered, on the basis of susceptibility test results. PMID- 8360092 TI - Sialadenitis associated with periorbital disease in a dog. AB - Submucosal sialadenitis was diagnosed on histologic examination of a biopsy specimen from a palatine swelling associated with acute, unilateral periorbital disease in a dog. Sialadenitis may have been the cause of periorbital disease or may have been part of a generalized inflammatory condition affecting the periorbital tissues. Corticosteroids were immediately effective in eliminating signs of periorbital disease and sialadenitis. A 3-month corticosteroid treatment was used because the sialadenitis and periorbital disease were immune-mediated. This dog has been free of recurring signs for more than 3 years. PMID- 8360094 TI - Proventriculotomy in ostriches: 18 cases (1990-1992). AB - Over a 3-year period, proventriculotomy was performed on 18 ostriches to relieve impaction of the proventriculus. Diagnosis was confirmed by abdominal palpation, abdominal radiography, and in some cases, exploratory proventriculotomy. In addition to proventriculotomy, an esophagotomy was performed in 5 birds that were debilitated to allow force-feeding during the postoperative period. The median age of ostriches treated surgically for proventricular impaction was 7.5 months (range, 3 months to 18 years). Impactions consisted of sand, rocks, or gravel in combination with grass, leaves, wood, or other fibrous materials. In 7 birds, small pieces of wire or nails were also removed from the proventriculus. In 1 bird, a large metal punch was removed via the proventriculotomy. Six ostriches died at the hospital in the immediate postoperative period. Four of these died within 24 hours of surgery. All 4 birds were emaciated and in a severely weakened condition at admission, and they continued to deteriorate after surgery. One bird died 8 days after surgery as a result of complications associated with a septic joint unrelated to the proventriculotomy procedure. Another bird was euthanatized 6 days after surgery because its condition failed to improve and the owners did not want to pursue further treatment because of expense. Follow-up information was obtained for 12 surviving ostriches 1 week to 29 months (median, 5.5 months) after they were discharged from the hospital. Four of the 12 birds died within 30 days of discharge from the hospital. The remaining 8 birds (44%) were alive at follow-up evaluation (median, 10.5 months after surgery; range, 5 to 29 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360095 TI - Scintigraphic evaluation of fractures of the distal phalanx in horses: 27 cases (1979-1988). AB - Retrospective radiographic and scintigraphic analyses were performed on 27 fractures of the distal phalanx in 25 horses. Location of 99mtechnetium methylene diphosphonate (99mTc-MDP) uptake was compared with fracture line location as seen on radiography. Intensity (intense, moderate, mild) and pattern (focal, diffuse) of 99mTc-MDP uptake was recorded and compared with duration of fracture. Nine horses were monitored during convalescence by obtaining additional scintigraphic views 3 to 68 months after injury. Palmar scintigraphic views had evidence of focal areas of increased 99mTc-MDP uptake that corresponded to fracture line location as seen on radiography. Lateral scintigraphic views had evidence of diffuse increased uptake. There was a significant (P < 0.01) association between duration of fracture and intensity of uptake, with fractures < 3 months in duration more likely to have intense focal uptake. All fractures < 10 days in duration had intense focal uptake. As fracture age increased, 99mTc-MDP uptake became less intense and more diffuse. Three fractures not evident on radiography had evidence of 99mTc-MDP uptake on scintigraphy. Stall rest resulted in decreased 99mTc-MDP uptake in 6 of 9 horses, but increased uptake was still visible in all horses between 4 and 25 months after injury. The only scintigraphic view without evidence of increased uptake was that obtained from a horse reexamined 68 months after injury. PMID- 8360096 TI - What is your diagnosis? Multiple, irregular, diffuse intraluminal masses in the urinary bladder. PMID- 8360097 TI - Tetrafibricin, a novel fibrinogen receptor antagonist. I. Taxonomy, fermentation, isolation, characterization and biological activities. AB - Tetrafibricin is a novel fibrinogen receptor antagonist produced by Streptomyces neyagawaensis NR0577. It was isolated from the culture broth by Diaion HP-21 adsorption, MeOH extraction, MCI GEL CHP-20P column chromatography, preparative HPLC and Toyopearl HW-40 SF column chromatography. The physico-chemical properties of tetrafibricin indicated that the structure of tetrafibricin is different from the known peptide fibrinogen receptor antagonists and closely related to the polyene macrolide antibiotics. Tetrafibricin strongly inhibited the binding of fibrinogen to its receptors with an IC50 of 46 nM. It also inhibited ADP-, collagen-, and thrombin-induced aggregation of human platelets with IC50s of 5.6, 11.0 and 7.6 microM, respectively. PMID- 8360098 TI - Tetrafibricin, a novel fibrinogen receptor antagonist. II. Structural elucidation. AB - The structure of tetrafibricin, a novel and potent fibrinogen receptor antagonist isolated from the culture broth of Streptomyces neyagawaensis NR0577, was determined. Tetrafibricin has a unique structure containing primary amine, conjugated tetraenoic acid, and polyhydroxy functionalities that is biosynthetically related to the polyene macrolide antibiotics. PMID- 8360099 TI - R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. I. Taxonomy, fermentation, isolation and biological properties. AB - New non-steroidal estrogen-receptor antagonists, R1128 A, B, C and D, were isolated from the cultured broth of Streptomyces sp. No. 1128 by solvent extraction, silica gel chromatography, reverse phase chromatography and preparative HPLC. These compounds inhibited estrogen binding to its receptor. The IC50 values of R1128 A, B, C and D for partially purified rat uterine cytosol receptor were 1.1 x 10(-7) M, 1.2 x 10(-7) M, 2.6 x 10(-7) M and 2.7 x 10(-7) M, respectively. PMID- 8360100 TI - R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. II. Physico-chemical properties and structure determination. AB - R1128 A, B, C and D, new non-steroidal estrogen-receptor antagonists, were isolated from the cultured broth of Streptomyces sp. No. 1128. Their structures were elucidated to be 1,3,6-trihydroxy-8-alkylanthraquinones on the basis of their physico-chemical properties and spectroscopic data. PMID- 8360101 TI - R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. III. Pharmacological properties and antitumor activities. AB - R1128 B (1,3,6-trihydroxy-8-n-butylanthraquinone), a new antibiotic produced by Streptomyces sp. No. 1128, inhibited estrogen binding to its receptor. The IC50 value of R1128 B for partially purified rat uterine cytosol receptor was 1.2 x 10(-7) M. However, the IC50 value of R1128 B against androgen-receptor binding was about 50-fold greater than that against estrogen-receptor binding. R1128 B was a competitive inhibitor against estrogen-receptor binding. R1128 B inhibited the growth of estrogen-responsive human mammary adenocarcinoma MCF-7 cells in soft agar. This inhibition, however, was reversed when estradiol was added to the culture medium. R1128 B showed antitumor activities against MCF-7 both xenografted to nude mice and implanted in subrenal capsule of mice (SRC assay). The potency of R1128 B was about 8-fold lower than that of tamoxifen both in vitro and in vivo. PMID- 8360102 TI - Vicenistatin, a novel 20-membered macrocyclic lactam antitumor antibiotic. AB - A new antitumor antibiotic vicenistatin was isolated from the culture broth of Streptomyces sp. HC34. The structure of vicenistatin was elucidated by NMR spectral analysis. Vicenistatin exhibited antitumor activity against human colon carcinoma Co-3 in the xenograft model. PMID- 8360103 TI - Eupenifeldin, a novel cytotoxic bistropolone from Eupenicillium brefeldianum. AB - Eupenifeldin was isolated from cultures of Eupenicillium brefeldianum ATCC 74184 by extraction and crystallization. The compound was identified as a pentacyclic bistropolone on the basis of spectral data and its complete structure was established by single-crystal X-ray analysis. The compound is cytotoxic against the HCT-116 cell line and has in vivo antitumor activity in the P388 leukemia model. PMID- 8360104 TI - UK-1, a novel cytotoxic metabolite from Streptomyces sp. 517-02. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties. AB - A new benzoxazole, UK-1, was isolated from the mycelial cake of an actinomycete strain 517-02. Based on morphological, cultural and physiological characteristics, strain 517-02 was seemed to be a close relative of Streptomyces morookaense. UK-1 showed potent cytotoxic activity against B16, HeLa and P388 cells and did not show any antimicrobial activity. PMID- 8360105 TI - UK-1, a novel cytotoxic metabolite from Streptomyces sp. 517-02. II. Structural elucidation. AB - The structure of UK-1 isolated from the mycelium of Streptomyces sp. 517-02 was elucidated to be a novel benzoxazole dimmer derivative (1) on the basis of spectroscopic methods. PMID- 8360106 TI - Antifungal macrocyclic polylactones from Penicillium verruculosum. AB - Three macrocyclic polylactones have been isolated from Penicillium verruculosum. Two were found to be novel and the third to be identical with NG-012(1). Their structures were elucidated by spectroscopic and chemical methods. A full assignment of 1H- and 13C-resonances in acetone-d6 are given for all three compounds. The compounds show antifungal activity. PMID- 8360107 TI - A novel macrolactam-disaccharide antifungal antibiotic. Taxonomy, fermentation, isolation, physico-chemical properties, structure elucidation and biological activity. AB - A novel natural product (1), with antifungal activity was isolated from the culture broth of an actinomadurae. The active compound was separated from broth by n-butanol extraction and purified by silica gel and multicoil counter current chromatography. Physico-chemical data suggested the structure of this compound to be a novel macrolactam disaccharide related to Sch 38518 (3). The structure was determined by spectroscopic studies on the acetate derivative. It was active against Candida spp. (MIC's, 4 approximately 64 micrograms/ml) but less than the monosaccharide, Sch 38518 (MIC's, 1 approximately 16 micrograms/ml). PMID- 8360108 TI - Isolation of trehalamine, the aglycon of trehazolin, from microbial broths and characterization of trehazolin related compounds. AB - Trehalamine, (3aR,4R,5S,6S,6aS)-2-amino-4-(hydroxymethyl)-3a,5,6,6a- tetrahydro 4H-cyclo-pent[d]oxazole-4,5,6-triol (1) and D-glucose were obtained by acid hydrolysis of trehazolin (3), a trehalase inhibitor produced by actinomycetes. More vigorous hydrolytic treatment of trehazolin afforded an aminocyclitol, (1R,2S,3R,4S,5R)-5-amino-1- (hydroxymethyl)cyclopentane-1,2,3,4-tetraol (2). Trehalamine, the aglycon of trehazolin, was also found in the culture broths of two trehazolin producing strains, Micromonospora sp. SANK 62390 and Amycolatopsis sp. SANK 60791. These trehazolin related compounds trehalamine (1) and 2 were poor inhibitors of trehalase (1; IC50 1.8 x 10(-4) M, 2; > 5.0 x 10(-4) M). On the other hand they inhibited more potently rat intestinal sucrase (1; IC50 6.8 x 10(-5) M) and sweet almond beta-glucosidase (2; IC50 5.6 x 10(-6) M) than trehazolin. PMID- 8360109 TI - Germicidin, an autoregulative germination inhibitor of Streptomyces viridochromogenes NRRL B-1551. AB - During germination spores of Streptomyces viridochromogenes NRRL B-1551 excrete a compound, germicidin, which has an inhibitory effect on the germination of its own arthrospores at a concentration as low as 200 pM (40 pg/ml). At higher concentrations germicidin inhibits porcine Na+/K(+)-activated ATPase and retards the germination of the cress Lepidium sativum. Germicidin is the first known autoregulative inhibitor of spore germination in the genus Streptomyces and was isolated from the supernatant of germinated spores, but also from the supernatant of the submerged culture. Spectroscopic analysis and derivatization reactions revealed germicidin to be 6-(2-butyl)-3-ethyl-4-hydroxy-2-pyrone (C11H16O3). Crude isolates of germicidin from the supernatant of submerged culture, but not from the spores, contained a second, structurally very similar compound (C10H14O3), in which in contrast to germicidin a 2-propyl instead of the 2-butyl chain was bound to C-6 and which did not show any activity in the germination and ATPase assay. The germination assay was evaluated as a new screening model for specifically active compounds. PMID- 8360110 TI - PC-766B, a new macrolide antibiotic produced by Nocardia brasiliensis. II. Isolation, physico-chemical properties and structure elucidation. AB - A new macrolide antibiotic, PC-766B, was isolated from the cells of Nocardia brasiliensis SC-4710 by acetone extraction, and purified by gel filtration, silica gel chromatography, HPLC and TLC. The structure of PC-766B was determined by NMR spectral analysis to be a new class of the hygrolidin family antibiotics. PC-766B had a 16-membered macrocyclic lactone ring, a 6-membered hemiketal ring and a 2-deoxy-D-rhamnose moiety. DL-alpha-Tocopherol, known as an antioxidant agent, significantly improved the stability of PC-766B and prevented the decomposition of PC-766B during the storage of the antibiotic. PMID- 8360111 TI - Delaminomycins, novel extracellular matrix receptor antagonist. IV. Structure activity relationships of delaminomycins and derivatives. AB - Delaminomycins A, B, C and their derivatives were prepared and investigated biological activities of them. Among these compounds, spiro compounds (A2, B2 and C2) showed stronger inhibitory activity than natural products (A1, B1 and C1) on B16 melanoma cells adhesion assay and Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, A1, B1 and C1 showed more potent inhibitory activity than spiro compounds (A2, B2 and C2). On the other hand, as to C-5' substituents of pyrrolidine ring, the order of inhibitory activity was R = OH > R = OCH3 > R = H on Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, the order of inhibitory activities were R = H > R = OCH3 > R = OH. Inhibitory activities of A4 which was lacked pyrrolidine ring were reduced on B16 melanoma cells adhesion assay and on cytotoxicity against tumor cells in vitro in comparison with those of A1. PMID- 8360112 TI - Chemical modification of erythromycins. XII. A facile synthesis of clarithromycin (6-O-methylerythromycin A) via 2'-silylethers of erythromycin A derivatives. PMID- 8360113 TI - Pyripyropenes, highly potent inhibitors of acyl-CoA:cholesterol acyltransferase produced by Aspergillus fumigatus. PMID- 8360114 TI - Chrysosporin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase produced by Chrysosporium pannorum. PMID- 8360115 TI - A novel producer of the antibiotic kirromycin belonging to the genus Actinoplanes. PMID- 8360116 TI - Synthesis of diolmycin analogs and their anticoccidial activities. PMID- 8360117 TI - The detection by a disc diffusion technique of inducible beta-lactamase in Yersinia enterocolitica. PMID- 8360118 TI - The effect of increased agar concentration in susceptibility testing media on MICs of antimicrobials for gram-negative bacilli. PMID- 8360119 TI - In-vitro activity of imipenem and amikacin combinations against resistant Pseudomonas aeruginosa. PMID- 8360120 TI - Effect of probenecid on cefazolin serum concentrations. PMID- 8360121 TI - Early diagnosis of systemic candidal infection. PMID- 8360122 TI - Selective decontamination of the digestive tract and its role in antimicrobial prophylaxis. AB - Selective decontamination of the digestive tract (SDD) is an established form of infection prevention which relies upon local antibiotic action to afford suppression of potential pathogens while preserving 'colonization resistance' (CR). However, CR has never been shown conclusively to play a decisive role in either achieving or maintaining effective prophylaxis in patients and by employing absorbable antimicrobials or parenteral antibiotics, prophylaxis is actually achieved by both local and systemic action. The role of prophylaxis in neutropenic patients is also far from clear since morbidity and mortality remain the same whether or not prophylactic antibacterials are given and most patients still require empirical therapy for fever. In addition, the Gram-positive cocci, rather than Gram-negative bacilli presently predominate as pathogens. There is also an increasing trend towards including fungal and viral infection as targets for prophylaxis. Moreover, current anti-infective strategies are more akin to 'pre-emptive therapy' (PET) since the antimicrobials are available systemically and given at optimum therapeutic doses and there is little to distinguish treatment given to prevent colonization from progressing to infection from that used to arrest incipient infection or effect a cure of established infection. In contrast, SDD as originally conceived may well prove cost-effective for the prevention of infection in intensive care although neither the optimum regimen nor the patient group who would gain most benefit have been defined. None the less, by affording protection against Gram-negative sepsis, both SDD and PET would reduce the pressure on the clinicians to treat empirically and shift the emphasis once more on appropriate investigations which would involve the microbiologist more directly and immediately in patient care. Any savings from lowering the drug usage could then be diverted to improving diagnosis and providing the regular monitoring that is essential to the success of both PET and SDD. PMID- 8360123 TI - Mutator plasmid in a nalidixic acid-resistant strain of Shigella dysenteriae type 1. AB - A clinical isolate of Shigella dysenteriae from Kashmir, resistant to seven antibacterial agents including nalidixic acid, carried four plasmids, only one of which was transferable by conjugation. This plasmid, designated pYD1, conferred trimethoprim resistance and increased the frequency of mutation to nalidixic acid resistance in recipient strains. Thus, although nalidixic acid resistance was not carried on a transferable plasmid, the presence of pYD1 increased the frequency at which the strain mutated to nalidixic acid resistance. PMID- 8360124 TI - The use of a DNA probe and PCR to examine the distribution of the aac(6')-Ic gene in Serratia marcescens and other gram-negative bacteria. AB - A nucleotide probe for the chromosomal aminoglycoside 6' acetyltransferase gene (aac(6')-Ic) of Serratia marcescens was used in non-radioactive dot-blot hybridization experiments with 186 strains belonging to ten different species of Serratia. The gene was only detected in strains of S. marcescens (all strains tested), and positive hybridization was seen irrespective of whether or not strains were kanamycin-resistant. An additional 180 strains belonging to 28 Gram negative bacterial species other than in the genus Serratia did not hybridize with the probe. A rapid PCR test for the aac(6')-Ic gene was developed and used to confirm that the aac(6')-Ic gene is only found in S. marcescens. Southern hybridization analysis of S. marcescens chromosomal DNA demonstrated that the gene was usually located on a PvuII fragment with a putative isoleucine tRNA-2 gene, but polymorphisms with respect to the size of this fragment were observed. PMID- 8360125 TI - Accumulation and killing kinetics of fifteen quinolones for Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. AB - The accumulation of fifteen quinolone antimicrobial agents (nalidixic acid, eight mono-fluorinated agents, three di-fluorinated agents and three tri-fluorinated agents) by Escherichia coli KL16, Staphylococcus aureus NCTC 8532 and Pseudomonas aeruginosa NCTC 10662 was studied. The concentration of quinolones accumulated varied with the quinolone and the bacterial species, and was not affected by the number of fluorine atoms on the quinolone nucleus. There was also no direct relationship between the hydrophobicity or the molecular size of each drug and accumulation or activity. The killing of the three strains by the fifteen quinolones at a concentration of 10 mg/L was determined in broth and phosphate buffer to mimic the conditions of the accumulation assay. The bactericidal activity varied with the agent and the strain, and usually reflected the in-vitro activity of the drug. Despite most agents causing a decrease in the viable count of the three strains there was no detectable effect on the pattern of accumulation of the quinolones. PMID- 8360126 TI - Studies on the postantibiotic effect and the postantibiotic sub-MIC effect of meropenem. AB - The postantibiotic effect (PAE), the postantibiotic sub-MIC effect (PA SME) and the sub-MIC effect (SME) of a new carbapenem, meropenem, were determined for different strains of Escherichia coli and Pseudomonas aeruginosa. A PAE was induced by 10 x MIC of meropenem for 2 h. After induction, the antibiotic was eliminated by washing and dilution. The strains in the postantibiotic exposure phase and the controls were then exposed to no antibiotic or to different sub MICs concentrations (0.1-0.6 x MIC) of meropenem. The growth curves were followed for 24 h with viable counts and/or measured by continuous monitoring of optical density in a BioScreen C apparatus. Zero or very low values for the PAE were seen in the strains studied. However, a long PA SME and SME were seen for P. aeruginosa when determined by both methods, which at 0.3 x MIC gave comparable results. At lower concentrations the PA SMEs measured with BioScreen C were shorter, probably due to differences in the definition between the two methods. The BioScreen C method was less laborious than viable counting. However, one disadvantage of the BioScreen C method was that manual viable counting still had to be used to determine bacterial killing. No PA SME or SME against E. coli was observed, and the increased sensitivity of P. aeruginosa to sub-MICs of carbapenems remains unexplained. PMID- 8360127 TI - Influence of methylprednisolone on the intracellular antimicrobial activity of erythromycin and clindamycin against Legionella pneumophila. AB - We have investigated the effect of methylprednisolone on the intracellular activity of erythromycin and clindamycin in vitro. An assay system was developed for the determination of intracellular activity of antibiotics against Legionella pneumophila using guinea pig resident alveolar macrophages. Erythromycin at a concentration of 0.625 mg/L (5 x MIC) and clindamycin at a concentration of 8 mg/L (MIC) inhibited the growth of a single strain of L. pneumophila in macrophages, whilst ceftizoxime at a concentration of 0.625 mg/L (5 x MIC) did not. Methylprednisolone at therapeutic concentrations did not affect the intracellular antibacterial activity of either erythromycin or clindamycin against L. pneumophila. We found no direct effect of methylprednisolone on the intracellular antibacterial activity of either erythromycin or clindamycin. PMID- 8360128 TI - Treatment of familial staphylococcal infection--comparison of mupirocin nasal ointment and chlorhexidine/neomycin (Naseptin) cream in eradication of nasal carriage. AB - Twenty-six families with recurrent staphylococcal infections were treated with either mupirocin nasal ointment (group M) or chlorhexidine neomycin (Naseptin) cream (group N) to the anterior nares, each combined with chlorhexidine soap for washing and chlorhexidine powder applied to other possible carriage sites. Patients receiving mupirocin following failure with chlorhexidine/neomycin (group M/N) were also treated. Treatment was given for seven days to 99 patients, 32 index (infected) patients and 67 family members. Follow-up swabs were collected by a study nurse 8, 14, 28, and 91 days after starting treatment. The carriage of Staphylococcus aureus in the anterior nares was 67%, in the axillae 22%, in the groin 23%, and perianal 19%. The carriage rates in the index patients was higher than family members, in all sites. The eradication of S. aureus from the nasal carriage site after therapy at 8 days was 95% in group M, 85% in group M/N and 61% in group N. Recolonization during the follow-up period was much less in those treated with mupirocin: 57% of patients in group M and 42% in group M/N were not carriers at 91 days, whereas 89% of patients group N were again colonized. Assessment clinically and in terms of prevention of further infective lesions showed that there was a higher response to mupirocin than to chlorhexidine/neomycin. Mupirocin nasal is a successful therapy for removing nasal carriage of S. aureus and has a prolonged effect on recolonization. PMID- 8360129 TI - Emergence of antibiotic resistance amongst Pseudomonas aeruginosa isolates from patients with cystic fibrosis. AB - We investigated the emergence of resistance to 15 anti-pseudomonal antibiotics amongst Pseudomonas aeruginosa isolates from 34 chronically colonized patients with cystic fibrosis by comparing the susceptibilities of strains isolated before 1987 and after 1989 from the same patients. Strains obtained after 1989 from a further 19 patients who were newly colonized served as controls. The 34 pairs of isolates demonstrated a marked increase in resistance which could not be accounted for by a general increase in resistance during the intervening years since the susceptibility patterns of strains isolated before 1987 were similar to those of strains isolated from patients in the control group. There was a strong correlation between this increase in resistance and both the frequency of admissions to and the number of days spent in hospital. Cluster analysis of the changes in susceptibility for individual antibiotics revealed four distinct patterns of resistance: the fluoroquinolones, with the exception of ofloxacin; the aminoglycosides; the ureidopenicillins and aztreonam; and the cephalosporins, carbapenems, carboxypenicillins and ofloxacin. We conclude that the long-term administration of anti-pseudomonal antibiotics to patients who are chronically colonized with P. aeruginosa is associated with the development of resistance. PMID- 8360130 TI - Monotherapy in serious hospital-acquired infections: a clinical trial of ceftazidime versus imipenem/cilastatin. European Study Group. AB - The clinical and bacteriological efficacy and safety of the antibiotics ceftazidime or imipenem/cilastatin in seriously ill patients with nosocomial infections were compared in a prospective, open, evaluator-blind, multicentre comparative trial. The study was performed in 26 European centres, the majority being intensive care units. Subjects were randomized to receive either ceftazidime 2 g bid or imipenem cilastatin 0.5 g qid given for at least five days after stratification for pneumonia, septicaemia or urinary tract infection (UTI). Three hundred and ninety-three patients with serious nosocomial infections (254 with pneumonia; 91 with septicaemia and 48 UTI were treated between February 1988 and January 1990 and their clinical and bacteriological response to antibiotic treatment assessed. There were no significant differences between ceftazidime and imipenem/cilastatin in clinical efficacy. The failure rates in evaluable patients were 22 and 26% in pneumonia, 23 and 19% in septicaemia and 0 and 5% respectively in those with UTI. Overall there was no significant difference between the two antibiotics for bacteriological response in the three infection strata. However, in patients with pneumonia ceftazidime was significantly more effective than imipenem/cilastatin in clearing patients of Pseudomonas spp.: 3/17 and 11/19 patients respectively had persistent growth of Pseudomonas spp. post-treatment (P = 0.004), and in one ceftazidime failure resistance emerged compared to six imipenem/cilastatin failures in which resistance emerged. Few drug-related adverse events were recorded in either treatment group. Monotherapy with either ceftazidime (2 g bid) or imipenem/cilastatin (0.5 g qid) is safe and effective and could be considered as an alternative to combination therapy for the treatment of serious hospital-acquired infections. PMID- 8360131 TI - Once- versus twice-daily amikacin regimen: efficacy and safety in systemic gram negative infections. Scandinavian Amikacin Once Daily Study Group. AB - Three hundred and sixteen patients with serious infections verified or suspected to be of Gram-negative aetiology were treated in an open, randomized, comparative multicentre study with amikacin 15 mg/kg/day given either as a single dose or in two divided doses at 12 h intervals. Two hundred patients were evaluated for efficacy and all 316 for safety. The efficacy of both dosage regimens was very good with a satisfactory clinical response in 90% of the patients. There were no significant differences between the two regimens regarding efficacy and safety. This was also confirmed in an analysis according to the principle of 'intention to-treat' including all randomized patients. In 218 patients additional therapy, most commonly with piperacillin or ampicillin, was considered necessary. The mean peak serum concentration of amikacin was 40.9 mg/L in the once-daily group, which is 10 x MIC for most Gram-negative bacteria, compared to 24.4 mg/L in the twice daily group, which is 6 x MIC. Mean trough serum concentrations after 24 h were 1.8 mg/L in the once-daily group and 3.1 mg/L after 12 h in the twice-daily group. These serum concentrations were often close to or just below the MICs of the isolated pathogens. Drug related adverse reactions were seen in 40 (13%) of the patients. Among the adverse reactions with possible or probable relation to amikacin were 20 nephrotoxic events, nine in the once-daily group and 11 in the twice-daily group. A multivariate analysis of selective causative factors and nephrotoxic events gave a low correlation for once- vs twice-daily amikacin therapy. Five ototoxic events were observed, three in the once-daily group and two in the twice-daily group. One patient in the once-daily group experienced nausea in connection with amikacin infusions. PMID- 8360132 TI - Loracarbef versus doxycycline in the treatment of acute bacterial maxillary sinusitis. Scandinavian Study Group. AB - In a double-blind, multicentre study, 662 patients with acute maxillary sinusitis were randomly assigned to receive either loracarbef 400 mg bd (332 patients) or doxycycline, 200 mg for the first dose followed by 100 mg od, (330 patients) for ten days. One hundred and sixty-eight patients in the loracarbef group and 164 in the doxycycline group were evaluable for efficacy. Streptococcus pneumoniae and/or Haemophilus influenzae were isolated from approximately 75% of patients. The clinical response rate (cure or improvement) was significantly higher for patients receiving loracarbef (98.2%) than for those who received doxycycline (92.2%). There was no significant difference between the two groups with respect to bacteriological outcome, although more of the pre-treatment isolates were resistant to doxycycline (35 strains) than to loracarbef (five strains). Adverse events related to the gastrointestinal tract occurred in 11.7% and 10.6% of loracarbef- and doxycycline-treated patients respectively; therapy was terminated prematurely in ten patients in the loracarbef group and in nine in the doxycycline group. The results indicate that loracarbef is effective and safe treatment for acute maxillary sinusitis. PMID- 8360133 TI - Clarithromycin versus cefaclor for the treatment of mild-to-moderate acute bacterial bronchitis. AB - Four hundred and eight outpatients with the clinical signs and symptoms of mild to-moderate acute bronchitis of bacterial aetiology were enrolled in a multicentre, double-blind, randomized clinical trial comparing the efficacy and safety of clarithromycin and cefaclor, both administered orally. Two hundred and seven patients received clarithromycin 250 mg bd and 201 patients received cefaclor 500 mg tds for a maximum of seven days. Clinical and bacteriological evaluations were performed before treatment was initiated, during the course of treatment, and within 72 h of completing therapy; all adverse events were recorded. Two hundred and three patients in the clarithromycin group and 195 in the cefaclor group were evaluable for clinical response and 129 and 124 patients in the clarithromycin and cefaclor groups, respectively, were evaluable for bacteriological response. The clinical response rates three to five days after starting treatment and at the post-treatment assessment were 97% (193/199) and 99.5% (202/203), respectively, for the clarithromycin group and 97.4% (187/192) and 97.9% (191/195), respectively, for the cefaclor group. The bacteriological cure rates were 94.6% (122/129) for the clarithromycin group and 90.3% (112/124) for the cefaclor group. None of the differences between the groups was statistically significant. Adverse events, which were generally mild and predominantly related to the gastrointestinal tract, were reported by 5.8% of clarithromycin-treated patients and 10.4% of cefaclor-treated patients. Adverse reactions caused one patient in the clarithromycin group and three in the cefaclor group to discontinue treatment prematurely. The results of this study indicate that clarithromycin and cefaclor are comparable with respect to efficacy and safety when used as treatment for patients with mild-to-moderate acute bacterial bronchitis. PMID- 8360135 TI - The management of infections and antibiotic therapy: a European survey. AB - A survey was undertaken in the five largest European countries in 1990/91 to measure the incidence of infectious diseases and record their antibiotic treatment, and usage as prophylaxis in acute general hospitals with over 300 beds. A representative sample of between 1234 and 1954 patient records were received for each country, with each participating clinician providing eight to ten records. Data were projected up to national totals. There were similarities between the patients across the countries, 50% of patients received surgery at some time in their hospital stay and in 45% the first antibiotic usage was as prophylaxis. In one fifth of the 55% treated for an infection, that infection was hospital acquired, but these 20% of patients accounted for 30% of total days in hospital for patients treated for infection. Infections of the lower respiratory tract, urinary tract and abdomen accounted for 75% of all infection cases. In 85% of infection cases, initial treatment was empirical. Overall, no culture and sensitivity data were reported by the end of treatment in over 50% of patients, with appreciable variation between the countries. In the UK, 60% of in-patient treatment was with oral antibiotics; in Italy, over 80% was injectable with over half that intramuscular. Germany had the highest rate of intravenous administration at nearly 60% of treatment days. Combination usage was highest, with over 30% of patient treatment days, in France and Spain, but Germany and Italy had the lowest usage at 21% and 16%. Mean duration of administration of antibiotics was shortest in the UK, eight days for infection and four days for prophylaxis, with France the longest at 12 days for infection, and Italy for prophyalxis at over five days. The UK had the highest rate of discharge on antibiotic treatment at over 30% of patients. Initial therapy was effective in about 90% of patients, but the UK, with the shortest durations and the greatest use of older antibiotics often as monotherapy and administered orally, had the highest rate of initial failure (> 10%) of both treatment of infection and prophylaxis. The result of initial failure was a significant prolongation of both hospital stay and antibiotic treatment. The 10% of initial treatment failures accounted for 15% of antibiotic usage in the UK. In France initial treatment failures were treated for twice the length of those in whom the initial therapy was successful.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360136 TI - Ovarian dysgerminoma: a therapeutic challenge. AB - Dysgerminoma remains a rare but quite interesting tumor. Over the last 40 years, the prognosis has markedly improved with a 5 year survival increasing from around 30% to more than 80%. Precise diagnosis and adequate staging are mandatory to define the best treatment approach aiming to cure the woman, while preserving her quality of life (ovarian function and fertility). PMID- 8360134 TI - Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group. AB - An open, randomized study was performed at 18 European centres to compare the efficacy, safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia. Five hundred and thirty-six hospitalized patients with malignant disease, about to receive chemotherapy, radiotherapy, or bone marrow transplantation, and who were already neutropenic or were expected to develop neutropenia were included in the study. Before therapy or transplantation, patients commenced either oral fluconazole therapy (50 mg/day as a single dose) or oral polyenes therapy (amphotericin B 2 g/day and/or nystatin 4 x 10(6) units/day in four or more divided doses), for a mean of 29.3 days and 31.3 days, respectively. After baseline clinical and mycological testing, patients were re evaluated at least weekly during prophylaxis, at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi. Fungal infection was diagnosed in 41 of 511 evaluable patients, 10 (3.9%) of 256 in the fluconazole group and 31 (12.2%) of 255 in the polyene group (P = 0.001). This total included four patients (1.6%) in the fluconazole group who developed oropharyngeal candidiasis compared with 22 (8.6%) in the polyene group (P < 0.001). Systemic infections comprised 6 (2.3%) in the fluconazole group and 9 (3.5%) in the polyene group (P = not significant), and included three Candida krusei infections in each group. Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 (24.2%) patients receiving fluconazole and 59 (23.1%) receiving polyenes (P = not significant). Colonization with fungi was generally similar in each treatment group, although an increased proportion of patients receiving fluconazole developed colonization of the faeces (P < 0.01). Adverse reactions, possibly related to treatment, were recorded in 15 (5.6%) of 269 patients in the fluconazole group and 14 (5.2%) of 267 in the polyene group; these necessitated discontinuation of therapy in seven patients in each group. Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia. PMID- 8360137 TI - Epidemiology and clinical aspects of testis tumors. PMID- 8360138 TI - Experience with high dose chemotherapy and autologous bone marrow transplantation in testicular cancer. AB - Carboplatin based HDCT followed by ABMT produces reasonable response rates (40 60%) and some durable remissions in patients with advanced and cisplatin resistant testicular cancer. Patients eligible for such an approach are those with primary refractory or recurrent disease and low probability for salvage by conventional dose regimens. The use of recombinant human growth factors and peripheral stem cell transplantation will probably reduce the toxicity and mortality of HDCT. PMID- 8360139 TI - Rat intestinal fatty acid binding protein. A model system for analyzing the forces that can bind fatty acids to proteins. PMID- 8360140 TI - Peptidomimetic inhibitors of Ras farnesylation and function in whole cells. AB - The ras protooncogene is involved in regulation of cell growth. Mutations that activate the protein result in uncontrolled cell growth. Ras undergoes a series of posttranslational processing events, the first of which, farnesylation, is crucial for the function of the protein. Inhibitors of the farnesyltransferase enzyme are therefore potential candidates for the development of anticancer drugs. Tetrapeptides have been reported to be good inhibitors of this enzyme in vitro. We have synthesized analogs of the tetrapeptide Cys-Val-Phe-Met by replacement of the amino-terminal amide bonds. One inhibitor, B581, is permeable to the cell membrane. In the cell, it inhibits processing of two farnesylated proteins, H-ras and lamin A, but it does not inhibit processing of a geranylgeranylated protein, Rap 1A. Microinjection of B581 into frog oocytes inhibits maturation induced by activated, farnesylated H-ras but not maturation induced by activated, geranylgeranylated H-ras or by progesterone. These results demonstrate that this peptide mimic inhibits farnesylation selectively in the cell. The inhibition of farnesylation results in inhibition of H-ras function. PMID- 8360141 TI - Identification of a small GTP-binding protein, Rab25, expressed in the gastrointestinal mucosa, kidney, and lung. AB - Small GTP-binding proteins have been implicated in the regulation of many dynamic cellular processes. The carboxyl termini of parietal cell small GTP-binding proteins were cloned using a 3'-rapid amplification of cDNA ends (RACE) technique with a degenerate oligonucleotide primer based on the WDTAGQE consensus GTP binding sequence. Six out of 53 clones demonstrated a novel Rab sequence, now designated Rab25. The complete sequence was obtained using 3'-RACE and revealed a deduced amino acid sequence having 63% identity with Rab11. The deduced amino acid sequence demonstrated a carboxyl-terminal CCQNI and also a novel GTP-binding site sequence of WDTAGLE. Nevertheless, recombinant Rab25 was able to bind GTP on blot. A major 1.2 kilobase Rab25 message was detected throughout the gastrointestinal mucosa and in lung and kidney tissue. No message was detected in brain, heart, liver, or skeletal muscle. In gastric tissue, Rab25 was absent in the bowel wall; among mucosal cells, it was highly enriched in parietal cells compared to chief cells. Rab25 mRNA was also detected in several colon carcinoma lines including LIM1215 and HT-29. The results indicate that Rab25 represents a novel member of the Rab family with an epithelial distribution. PMID- 8360142 TI - Cleavage of cellubrevin by tetanus toxin does not affect fusion of early endosomes. AB - Tetanus toxin is a potent inhibitor of neurotransmitter release, which acts as an intracellular metalloendoprotease that selectively cleaves synaptobrevin, a major membrane protein of synaptic vesicles. Recently, synaptobrevin has been found to form an ATP-dependent complex with N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein, which are known to function in endosome fusion. Furthermore, a highly homologous isoform of synaptobrevin, named cellubrevin, was identified that is expressed in virtually all tissues in the endocytic pathway and is cleaved by tetanus toxin light chain in vitro, suggesting that cellubrevin may have a general function in intracellular fusion events. In the present study, we have analyzed whether cleavage of cellubrevin by tetanus toxin influences the ATP-dependent, N-ethylmaleimide-sensitive fusion of early endosomes in vitro. Our results show that endosome fusion is not affected by tetanus toxin although cellubrevin is almost completely proteolyzed, suggesting that the function of NSF in endosome fusion does not involve cellubrevin. PMID- 8360143 TI - The role of phosphorylation in activation of the alpha 6A beta 1 laminin receptor. AB - The phorbol ester phorbol 12-myristate 13-acetate (PMA) induces phosphorylation of serine residues in the cytoplasmic domain of the alpha 6A integrin subunit, as well as activation of the alpha 6A beta 1 laminin receptor. We examined whether phosphorylation correlates with the induction of high affinity binding of laminin by the alpha 6A beta 1 receptor. Two potential phosphorylation sites for protein kinase C, serine 1041 and serine 1048, are present in the cytoplasmic domain of the alpha 6A subunit. We introduced point mutations into the alpha 6A cDNA, replacing either one or both of the serine residues with alanine. Wild-type and mutant alpha 6A cDNAs were transfected into K562 cells. All alpha 6A subunit mutants were expressed at levels similar to those of wild-type alpha 6A and formed heterodimers with endogenous beta 1. Analysis of the phosphorylation state of wild-type and mutant alpha 6A subunits in resting K562 cells and after treatment with PMA showed that serine 1041, but not serine 1048, is the target residue of PMA-induced phosphorylation. Cells expressing alpha 6A mutant subunits or wild-type alpha 6A transfectants all bound laminin in the presence, but not in the absence of PMA; however, the extent of binding differed. Cells transfected with alpha 6A containing the serine to alanine mutation showed a 2-3-fold higher binding to laminin than cells transfected with alpha 6A containing serine 1041. The results indicate that phosphorylation of the alpha 6A cytoplasmic domain is not required for the induction of high affinity of the alpha 6A beta 1 receptor by PMA, and suggest that, in contrast, it may reduce the affinity of this integrin for ligand. PMID- 8360144 TI - Cell cycle-dependent suppressive effect of histone H1 on mitosis-specific H3 phosphorylation. AB - To analyze the mechanism by which histone H3 phosphorylation occurs specifically during mitosis, the effect of H1 on mitosis-specific H3 phosphorylation (Ser-10) was investigated in nucleosomes. H1 interaction with H1-depleted nucleosomes suppressed H3 phosphorylation including Ser-10 by approximately 50%. However, H1 interaction with DNA-free histone octamers failed to suppress H3 phosphorylation. The extent of suppression of H3 phosphorylation in nucleosomes with H1 prepared from synchronized HeLa cells was cell cycle-dependent. Binding with a highly phosphorylated mitotic H1 produced the least suppression of H3 phosphorylation, whereas binding with a lower H1 phosphorylation from G1 phase resulted in the greatest suppression. The results suggest that 1) mitotic H3 phosphorylation is suppressed with a lower level of H1 phosphorylation during interphase and 2) highly phosphorylated H1 during mitosis partially releases the suppression of mitotic H3 phosphorylation. PMID- 8360146 TI - Direct energization of bile acid transport into plant vacuoles. AB - Bile acids were shown to be transported into barley mesophyll vacuoles. Uptake of the cholate conjugates taurocholate and glycocholate is strictly ATP-dependent. Uptake of taurocholate is a saturable process (Km = 40 microM) and is inhibited by vanadate but not by bafilomycin, a specific inhibitor of the vacuolar H(+) ATPase. Together with the observation that the non-hydrolyzable ATP analog AMPPNP (5'-adenylyl beta,gamma-imidodiphosphate) does not stimulate, but rather inhibits, the ATP-dependent uptake of taurocholate, and that a 3-fold accumulation of the bile acid is observed in the presence of bafilomycin, these results suggest that taurocholate is transported into the vacuole by a primary active process as is the case for its canalicular secretion in rat liver (Nishida, T., Gatmaitan, Z., Che, M., and Arias, I. M. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 6590-6594). Taurocholate uptake is inhibited by other bile acids and is slightly stimulated by glutathione S-conjugates. The different responses of the glutathione S-conjugate (Martinoia, E., Grill, E., Tommasini, R., Kreuz, K., and Amrhein, N. (1993) Nature 364, 247-249) and the taurocholate transporters, respectively, to substrates, oligomycin, GTP, and UTP suggest the presence of at least two ATPases specifically involved in the transport of conjugates across the tonoplast. As cholate and its conjugates have so far not been reported to occur in plants, the physiological function of the novel transport ATPase described here is presently unknown. PMID- 8360145 TI - Germline manipulation of glucose homeostasis via alteration of glucose transporter levels in skeletal muscle. AB - Transgenic mice were constructed that overexpress the human Glut1 glucose transporter in skeletal muscle. Transcription of the human Glut1 cDNA was driven by the rat myosin light chain 2 promoter. Soleus and quadriceps muscles from transgenic mice expressed increased levels of Glut1 protein relative to muscles obtained from nontransgenic littermates, but there was no difference in the level of Glut4 protein between the two groups. Skeletal muscles isolated from the transgenic animals exhibited 3-4-fold increases in basal glucose uptake relative to muscles obtained from nontransgenic littermates. Muscles isolated from nontransgenic littermates exhibited 2-3-fold increases in glucose transport after incubation in the presence of insulin, but no insulin-stimulated increase in transport was observed in the muscles of transgenic mice. Plasma glucose levels were reduced by 18 and 30%, respectively, in fed and fasted transgenic mice relative to their nontransgenic siblings, but insulin and glucagon levels were not significantly different between the two groups. Glucose disposal following an oral glucose load was markedly enhanced in the transgenic animals, and plasma lactate and beta-OH-butyrate levels were elevated in both fed and fasted transgenic mice. These data strongly support the hypothesis that glucose transport plays a key role in whole body glucose homeostasis. They also demonstrate that the level of a glucose transporter in skeletal muscle can significantly influence the blood glucose set point and alter the levels of other fuel metabolites in the blood. PMID- 8360147 TI - The structure of Leishmania major amastigote lipophosphoglycan. AB - Intracellular amastigotes of Leishmania major produce 6 x 10(4) copies/cell of a lipophosphoglycan (LPG) that is structurally distinct from the LPG produced by the extracellular promastigote form of L. major, Leishmania donovani, and Leishmania mexicana (reviewed by McConville, M. J. (1991) Cell Biol. Int. Rep. 15, 779-798). L. major amastigote LPG is composed of a lysoalkyl phosphatidylinositol lipid anchor that links via a diphosphorylated hexasaccharide core to a phosphoglycan (6-100 kDa). The structures of the anchor, the core, and the phosphoglycan were determined by monosaccharide and linkage analysis, fast atom bombardment-mass spectrometry, one-dimensional 1H NMR spectroscopy, and exoglycosidase microsequencing. The lipid anchor contains predominantly 1-O-alkylglycerols with 24:0 and 22:0 alkyl chains. The lipids are linked via a glycerol-myo-inositol-PO4 to a core glycan with the structure -PO4 6)Gal(alpha 1-)Gal(alpha 1-) Galf(beta 1-)[Glc(alpha 1-PO4-)]Man(alpha 1 )Man(alpha 1-)GlcN(alpha 1-). The chromatographic characteristics of the core glycan suggest that the saccharide components are linked similarly in amastigote and promastigote LPG. The phosphoglycan attached to the core consists of -PO4 6)Gal(beta 1-4)Man(alpha 1- repeats units which are either unsubstituted (70%) or substituted (30%) at the 3-position of the Gal residues with oligosaccharide side chains containing primarily Gal and some Glc. Thirteen different types of side chains were identified with the structures [Gal(beta 1-3)]x, where x = 1-11, or Glc(1-3)Glc(1-3), or Glc(1-3)Gal(beta 1-3), where glucose is probably in the beta configuration. All monosaccharides in the phosphoglycan domain are in the pyranose configuration. The average number of repeat units per molecule is 36. The nonreducing terminus of the phosphoglycan chains probably terminates predominantly in the neutral disaccharide Gal(beta 1-4)Man(alpha 1-. Comparison of the structure of L. major amastigote LPG to L. major promastigote procyclic and metacyclic LPG forms (McConville, M. J., Turco, S. J., Furguson, M. A. J., and Sacks, D. L. (1992) Embo J. 11, 3593-3600) indicates that this molecule is developmentally modified throughout the different stages of the parasites' life cycle. PMID- 8360148 TI - Ligand-specific dimerization of the extracellular domain of the bovine growth hormone receptor. AB - The bovine growth hormone (bGH) receptor and its extracellular domain (bGHBP) bind two protein hormones with high affinity; bGH and bovine placental lactogen (bPL). However, each of these hormones bind with a different stoichiometry. bGH binds to the bGHBP in a 1:2 ratio while bPL binds in a 1:1 ratio. Scatchard analysis of saturation binding yields similar apparent dissociation constants (Kd) for bGH and bPL of 1.4 x 10(-11) M and 3.0 x 10(-11) M, respectively, for the membrane receptor and 6.8 x 10(-11) M and 4.2 x 10(-11) M, respectively, for bGHBP. In competition experiments using either liver membranes or bGHBP, bGH is 2 3-fold more effective than bPL in competing for 125I-bGH-binding sites. In similar experiments using 125I-bPL, bPL is 50-fold more effective than bGH in competing for binding sites. A rat monoclonal antibody raised against bGHBP competes effectively for 125I-bGH-binding sites, but not for 125I-bPL-binding sites. Since bPL cannot dimerize the bGHBP and yet it acts in part as a somatogen in vivo, homodimerization of the growth hormone receptor is apparently not essential for some biological responses signaled through this receptor. PMID- 8360149 TI - Identification of a transcript that is down-regulated in senescent human fibroblasts. Cloning, sequence analysis, and regulation of the human L7 ribosomal protein gene. AB - Normal eukaryotic cells divide only a limited number of times before proliferation ceases due to cellular senescence. We previously reported that a constitutively expressed, non-cell cycle-regulated transcript of unknown identity declines severalfold when human fibroblasts become senescent. We show here, from the sequence of cDNA and genomic clones, that this transcript encodes L7, a structural protein of the large ribosomal subunit. The human L7 protein shares > 90% amino acid identity with the mouse and rat L7 proteins but is shorter than either rodent protein due to fewer basic repetitive motifs at the amino terminus. The position of the first intron is conserved between the mouse and human genes. The L7 mRNA was abundant, stable (t1/2 > 10 h), and polyadenylated in presenescent and senescent human fibroblasts; however, steady state mRNA levels were 5-10-fold lower in senescent cells, whether derived from fetal lung or neonatal foreskin. Quiescent and senescent cells synthesized protein at similar rates, yet only senescent cultures showed a decline in L7 mRNA. The mRNAs encoding five other ribosomal proteins (L5, P1, S3, S6, and S10) behaved similarly. The results suggest that the senescence-associated decline in L7 and other ribosomal protein mRNAs is unrelated to growth state or protein synthetic rate per se and support the view that senescence and quiescence are dissimilar states. PMID- 8360150 TI - Utilization of conformational flexibility in enzyme action-linkage between binding, isomerization, and catalysis. AB - An intimate relationship between protein conformational changes and catalysis has often been suggested. The present study employs ligand-induced ultraviolet difference spectra and kinetic parameters determined for Escherichia coli ornithine transcarbamoylase and its site-specific mutants to evaluate the linkage between binding, isomerization, and reaction rate. For the wild-type enzyme, the lead substrate carbamoyl phosphate introduces a large difference absorbance in the enzyme upon binding (delta epsilon max approximately 1,800 M-1 cm-1; Miller, A. W., and Kuo, L. C. (1990) J. Biol. Chem. 265, 15023-15027). The spectrum is the same in lineshape as that produced by the bisubstrate analog N (phosphonacetyl)-L-ornithine and is 80% as intense. Both substrate and analog cause gross protein conformational rearrangements as evident by swift and severe cracking of enzyme crystals in their presence. For the mutants, the difference spectra actuated by the substrate are the same in lineshape as that of the wild type but vary in intensity. A wide range of substrate affinity and steady-state kinetic constants are also observed for the mutants. When the binding energy of carbamoyl phosphate and the activation energy for transcarbamoylation are calculated for the wild-type and mutant enzymes, they are found to be inversely correlated to the intensity of protein difference absorbance elicited by the lead substrate. Together with analyses of steady-state kinetic parameters derived for various plausible reaction schemes, the experimental data suggest that carbamoyl phosphate induces the committed isomerization in ornithine transcarbamoylase for transition state binding. Our results provide a unique demonstration that an induced-fit isomerization, triggered by binding, either controls or contributes significantly to the rate of an enzyme-catalyzed reaction. PMID- 8360151 TI - The oxidation of blood plasma and low density lipoprotein components by chemically generated singlet oxygen. AB - Human blood plasma and freshly isolated LDL were exposed to singlet oxygen (1O2) by thermal decomposition of synthetic endoperoxides. Exposure of blood plasma to 20 mM water-soluble 1O2 generator resulted in the depletion of ascorbate (100%), urate (75%), ubiquinol-10 (65%), protein thiols (50%), and bilirubin (25%), whereas under these conditions the levels of alpha-tocopherol, beta-carotene, and lycopene remained unchanged. The following rates of depletion were obtained by kinetic analysis (moles depleted per 100 mol of 1O2 consumed): protein thiols (5), urate (5), ascorbate (4), bilirubin (1), and ubiquinol-10 (0.008). In contrast, the rates of depletion using the lipid-soluble 1O2 generator were faster for bilirubin (13-fold), protein thiols (9-fold), ubiquinol-10 (8-fold), and ascorbate (5-fold), and slower for urate (2-fold). The formation of lipid hydroperoxides, including mostly cholesteryl linoleate hydroperoxide, was observed in 1O2-treated plasma (0.007-0.009 mol/100 mol 1O2) and LDL solutions (0.086 mol/100 mol 1O2). Based on competition kinetics, we estimate that 98% of 1O2 generated in the aqueous phase of plasma is quenched by components in this phase, mostly by plasma protein (63%; 6% by protein thiols), urate (9%; 5% by chemical quenching), and bilirubin (5%; 1% by chemical quenching). Ascorbate and ubiquinol-10 do not contribute to 1O2 quenching in plasma, and their oxidation is probably mediated secondary species. The remaining 1O2 generated in plasma (2%) diffuses into lipoprotein leading to the formation of lipid hydroperoxides with an efficiency of about 100-fold greater than that compared to aqueous generated 1O2. The principal 1O2 quenchers in LDL include apoB (42%), lycopene and beta carotene (40%), and alpha-tocopherol (17%). The importance of carotenoids in the quenching of 1O2 in lipoprotein suggest that the beneficial effects of these compounds in health may in part be due to the elimination of this species in biology and medicine. PMID- 8360152 TI - Affinity radiolabeling identifies peptides and amino acids associated with substrate binding in human placental 3 beta-hydroxy-delta(5)-steroid dehydrogenase. AB - Purified human placental 3 beta-hydroxy-delta(5)-steroid dehydrogenase (3 beta HSD) was affinity radiolabeled by 2 alpha-bromo[2'-14C]acetoxyprogesterone (2 alpha-BAP) in the presence or absence of 3 beta-HSD substrate, pregnenolone. The substrate steroid substantially protects 3 beta-HSD activity from inactivation by 2 alpha-BAP. Tryptic peptides of unprotected and substrate-protected radioalkylated enzyme were purified by high pressure liquid chromatography. The amino acid sequence of each radiolabeled peptide was determined and localized within the cDNA-derived primary structure of the enzyme. According to the percent total radioactivity associated with each of four radiolabeled peaks separated by high pressure liquid chromatography, two peptides were protected by substrate from affinity radioalkylation by 2 alpha-BAP. The first, 251GQFYYISDDTPHQSYDNLNYTLSK274, was produced by tryptic cleavage at Arg-250 and Lys-274 (the Arg-250 peptide) and contained radiolabeled His262. The second, 176NGGTLYTCALR186, was produced by tryptic cleavage at Lys-175 and Arg-186 (the Lys-175 peptide) and contained radiolabeled Cys183. Based on amino acid analysis to quantitate radioactivity incorporated per nmol of peptide, substrate steroid decreased the radiolabeling of His262 in the Arg-250 peptide by 3.6-fold and decreased the radiolabeling of Cys183 in the Lys-175 peptide by 3.7-fold. Three minor radiolabeled peptides (the NH2-terminal, Arg-71, and Arg-196 tryptic peptides) were also identified in the primary structure, but pregnenolone did not diminish their affinity radioalkylation. These observations indicate that the Arg 250 and Lys-175 peptides are involved in substrate binding and suggest that His262 and Cys183 are in close proximity in the three-dimensional structure of the enzyme. PMID- 8360153 TI - Binding of cerebrosides and sulfatides to saposins A-D. AB - Saposins are a family of four small glycoproteins, all of which are derived from prosaposin, and are involved in the lysosomal hydrolysis of various sphingolipids. Results from this investigation demonstrate that saposins A-D bind to galactosyl- and glucosylceramide. The binding was highly dependent on the solution pH; maximum binding of glucosylceramide to all saposins occurred at pH 7. Maximum binding of galactosylceramide to saposins B and D occurred at a more basic pH (8.5). The binding of glucosylceramide to saposins was significantly inhibited by Mg2+, Ca2+, or Zn2+. Although maximum binding of sulfatide to saposins A, C, and D occurred at acidic pH, the binding to saposin B was maximum at pH 8.5. Saposin A also bound sphingomyelin or phosphatidylcholine at neutral pH. No significant binding was evident between these lipids and saposins B-D at any pH value. The existence of saposin-lipid complexes was further confirmed in selected samples by gel filtration, isoelectric focusing, and a TLC binding assay. We have also shown that galactosylceramide bound to saposins A-D was efficiently transported to a rat brain microsomal fraction. This result suggests that saposins and possibly their precursor, prosaposin, may be involved in membrane biogenesis such as the assembly of myelin and plasma membranes. PMID- 8360155 TI - Characterization of the ATP-dependent binding of wheat germ protein synthesis initiation factors eIF-(iso)4F and eIF-4A to mRNA. AB - The ATP-dependent binding of wheat germ protein synthesis initiation factors eIF (iso)4F and eIF-4A to an oligoribonucleotide has been investigated by direct fluorescence titration techniques. In addition, the effect of ATP on the interaction between another cap-binding initiation factor, eIF-4F, and eIF-4A was studied using the same methods. Comparison of the equilibrium association constants (K(eq)) indicate that 1) hydrolyzable ATP affects the affinity of eIF (iso)4F for eIF-4A, regardless of whether or not mRNA was previously bound to the eIF-(iso)4F; in contrast, ATP had no effect on the eIF (iso)4F/oligoribonucleotide interaction; 2) in the presence of ATP, the binding of the binary eIF-(iso)4F.eIF-4A complex to the oligoribonucleotide is of similar affinity as the binding of the oligoribonucleotide to the eIF-(iso)4F alone; the stoichiometry of this ternary eIF-(iso)4F.eIF-4A.mRNA complex was found to be 1:1:1; and 3) a similar ATP effect is observed for the eIF-4F/eIF-4A interaction as for the eIF-(iso)4F.eIF-4A complex. PMID- 8360154 TI - Inhibition of neutrophil NADPH oxidase assembly by a myristoylated pseudosubstrate of protein kinase C. AB - To further define the role played by protein kinase C (PKC) in the activation of the neutrophil NADPH oxidase, we have utilized a pseudosubstrate of PKC which was myristoylated at the N terminus. In electropermeabilized neutrophils, the myristoylated pseudosubstrate Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln (myr-psi PKC) inhibited PMA-induced protein phosphorylations and activation of the NADPH oxidase, induced either by PMA or by the receptor agonist formyl-methionyl-leucyl phenylalanine. Both the pseudosubstrate lacking the N-terminal myristate (psi PKC) and a myristoylated control peptide (Phe-Ala-Glu-Asp-Gly-Ala-Leu-Glu-Gln, myr-CP) were without effect on these responses. The myristoylated pseudosubstrate was also tested in a cell-free system, in which NADPH oxidase activation can be achieved by addition of SDS and guanosine 5'-3-O-(thio)triphosphate in a staurosporine-insensitive manner. Myr-psi PKC, but not psi PKC or myr-CP, proved to be a potent inhibitor of NADPH oxidase activity in the cell-free system, indicating that the inhibition observed in permeabilized neutrophils may have been caused by an effect other than PKC inhibition. In the presence of myr-psi PKC, translocation in the cell-free system of the cytosolic oxidase components p47-phox and p67-phox to the plasma membrane was inhibited. From these results we conclude that myristoylation profoundly increases the ability of pseudosubstrates of PKC to inhibit not only PKC-mediated phosphorylations, but also NADPH oxidase activation. The latter effect, however, is most probably not related to PKC inhibition but may indicate a critical role of the membrane surface charge in the translocation of the cytosolic oxidase components p47-phox and p67-phox. PMID- 8360156 TI - NADPH-sulfite reductase from Escherichia coli. A flavin reductase participating in the generation of the free radical of ribonucleotide reductase. AB - Protein R2, the small subunit of ribonucleotide reductase of Escherichia coli, contains an essential free radical localized to tyrosine 122 of its polypeptide chain. When this radical is scavenged by hydroxyurea, the enzyme is transformed into an inactive form, metR2. E. coli contains a NAD(P)H:flavin oxidoreductase, named Fre, absolutely required for the regeneration of the radical and the activation of metR2 into R2. Consequently, an E. coli mutant strain lacking an active fre gene is more sensitive to hydroxyurea during growth, demonstrating the physiological protective function of Fre from the loss of the radical. However, this gene is not essential, and we found that E. coli contains a second tyrosyl radical generating activity, also residing in a flavin reductase. The enzyme has been purified 200-fold to homogeneity and found to be identical to sulfite reductase. Pure sulfite reductase has the ability to catalyze the reduction of free riboflavin, FMN, or FAD by NADPH and thus, as Fre, to transfer electrons to the iron center of metR2, a key step during the activation reaction. PMID- 8360157 TI - The ATP-binding cassette (ABC) transporter for maltose/maltodextrins of Salmonella typhimurium. Characterization of the ATPase activity associated with the purified MalK subunit. AB - The ATPase activity associated with the purified MalK subunit of the maltose transport complex of Salmonella typhimurium, a bacterial ATP-Binding Cassette (ABC) transporter (Walter, C., Honer zu Bentrup, K., and Schneider, E. (1992) J. Biol. Chem. 267, 8863-8869), was characterized in detail. The analysis of the kinetics of ATP hydrolysis yielded a Km value of 70 +/- 4 microM and a Vmax of 1.3 +/- 0.3 mumol/min/mg of protein. Both GTP and CTP also served as substrates. While MalK exhibited nearly the same affinity for GTP as for ATP, the Michaelis constant for CTP as a substrate was much higher. ATP hydrolysis was strongly dependent on the presence of Mg2+ ions. Mn2+ at low concentrations, but neither Ca2+ nor Zn2+ partially substituted for Mg2+. The ATPase activity was optimal at slightly alkaline pH and was stimulated in the presence of both glycerol (7.5%) and dimethyl sulfoxide (Me2SO) (5%). ADP and the non-cleavable substrate analog ATP gamma S (adenosine 5'-O-(3-thiotriphosphate)) were identified as competitive inhibitors. The MalK-ATPase was resistant to specific inhibitors of F-, P-, and V type ATPases, such as dicyclohexylcarbodiimide, azide, vanadate, or bafilomycin A1. In contrast, micromolar concentrations of the sulfhydryl reagent N ethylmaleimide strongly inhibited the enzymatic activity. This inhibition was blocked in the presence of ATP. These results suggest that the intrinsic ATPase activity of purified MalK can be clearly distinguished from other ATP-hydrolyzing enzymes, e.g. ion-translocating ATPases. PMID- 8360158 TI - Cloning and characterization of a 23-kDa stress-induced mouse peritoneal macrophage protein. AB - Exposure of mouse peritoneal macrophages to oxidative and sulfhydryl-reactive agents in vitro enhances synthesis of a few cellular proteins that may be important in a self-defense system. A cDNA encoding a novel stress-inducible protein, designated MSP23 (macrophage 23-kDa stress protein), was cloned from a cDNA library of the macrophages by differential screening. A 1.0-kilobase mRNA transcript hybridized with the MSP23 cDNA gradually increased in macrophages upon culture in vitro. Treatment with diethylmaleate or glucose/glucose oxidase, which generates H2O2, markedly enhanced the induction of the transcript after several hours. Cadmium chloride and sodium arsenite also induced the transcript. An antiserum raised against recombinant MSP23 reacted with the 23-kDa stress inducible protein of the macrophages. The amounts of 23-kDa protein in the cells rapidly increased during culture with diethylmaleate. The mRNA was detected in various tissues, and it was especially high in content in the liver. A search of databases revealed that six proteins of various species from bacteria to the mouse have a sequence homology to MSP23. One of the proteins is the C22 component of alkyl hydroperoxide reductase, which is induced by hydrogen peroxide in Salmonella typhimurium. PMID- 8360159 TI - Determination of the intrinsic Michaelis constant of immobilized alpha chymotrypsin. AB - The Michaelis constant of alpha-chymotrypsin, immobilized on a glutaraldehyde activated silicate support, for N-glutaryl-L-phenylalanine-p-nitroanilide was determined and was found to be identical with that of the enzyme in solution. The influence of intraparticular diffusion was taken into account by immobilizing different amounts of enzyme, thus changing the magnitude of diffusional constraints and extrapolating apparent Michaelis constants, determined for each amount of immobilized enzyme, to zero diffusional constraints. The possible effect of the immobilized enzyme distribution inside the porous matrix was investigated through numerical simulations. PMID- 8360160 TI - Calcium responses elicited by nucleotides in macrophages. Interaction between two receptor subtypes. AB - The responses elicited by ATP and UTP in macrophages (measured by microfluorescence and in patch-clamp) present marked differences. The release of Ca2+ from intracellular stores induced by ATP is due to the activation of P2U receptors. These receptors can be activated by ATP4- and by MgATP2-, with apparent K0.5 values of 0.65 and 6.5 microM, respectively. The release of Ca2+ due to activation of P2U receptors by either ATP or UTP is followed by the opening of ionic channels leading to an influx of Ca2+. A second pathway for Ca2+ influx results from the opening of P2Z receptor channels triggered by adenosine 5'-O(1-thiotriphosphate) or ATP but not by UTP. The form of ATP that activates P2Z receptors is ATP4- (with a K0.5 of 0.5 microM). In voltage-clamped cells, the inward current activated by ATP4- is transient, partly because it inactivates and partly because it is rapidly masked by the development of a quinine-sensitive Ca(2+)-dependent K+ current. In current-clamp, macrophages stimulated by UTP remain normally polarized, whereas ATP depolarizes them. This P2Z-mediated depolarization results in an inhibition of the influx of Ca2+, which explains part of the difference between the time courses of the Ca2+ responses elicited by ATP and UTP. PMID- 8360161 TI - The pattern of agonist-evoked cytosolic Ca2+ oscillations depends on the resting intracellular Ca2+ concentration. AB - The agonists acetylcholine (ACh) and cholecystokinin (CCK) have been shown to evoke markedly different patterns of cytosolic Ca2+ oscillations in the same isolated pancreatic acinar cells. ACh induces high frequency sinusoidal oscillations (spiking) associated with activation of Ca2+ influx. CCK evokes longer lasting discrete transients separated by long intervals, and these low frequency transients persist for many minutes in the absence of extracellular Ca2+. Using digital imaging of fura-2 fluorescence, we have now monitored the free cytoplasmic Ca2+ concentration ([Ca2+]i) simultaneously in many individual cells from the same population. In the resting condition [Ca2+]i ranged from about 50 to 300 nM. When the resting [Ca2+]i was below 150 nM, ACh (50-100 nM) invariably evoked typical high frequency spiking. In the majority of cells which had a resting [Ca2+]i higher than 150 nM, ACh also evoked low frequency transients. Although initiated by ACh, these transients displayed the temporal and functional characteristics of the CCK-evoked transients. Removal of extracellular Ca2+ for a few minutes had no effect on this type of oscillation, whereas such a procedure reversibly abolished the ACh-evoked high frequency response. For the response evoked by 10-30 pM Ca2+ signal amplitude and the resting [Ca2+]i. Because the Ca2+ signal amplitude and the resting [Ca2+]i. Because CCK could never induce high frequency spiking there is some receptor specificity in dictating the time course of Ca2+ oscillations, but the resting [Ca2+]i is a major determinant of the Ca2+ signal pattern. PMID- 8360162 TI - Surfactant protein A-binding proteins. Characterization and structures. AB - An alveolar cell membrane protein acts as a surfactant protein A (SP-A) receptor; it binds SP-A and regulates surfactant secretion. We identified such alveolar cell membrane SP-A-binding proteins using anti-idiotype antibodies directed against the surfactant protein binding region of anti-surfactant antibodies. These monoclonal anti-idiotype antibodies, A2C and A2R, also recognize an alveolar cell membrane protein of approximately 30 kDa. A pulmonary protein of approximately 30 kDa binds SP-A. Unique cDNAs encoding this protein were identified in human (4.1-kilobase) and porcine (1.8-kilobase) lung expression libraries. Coding regions of these cDNAs cross-hybridize with each other under stringent conditions. Both cDNAs encode similar approximately 32-kDa proteins that bind SP-A. The human and porcine SP-A recognition (SPAR) proteins resemble each other, as well as other cell membrane receptors. Their projected structures are consistent with cell membrane receptors. Recombinant human and porcine SPAR proteins bind SP-A as well as the two anti-idiotype antibodies just as do native lung proteins of approximately 30 kDa. SPAR transcripts are expressed primarily in lung. The cellular distribution of these transcripts, as determined by in situ hybridization, is similar to that of SPAR protein, as determined by immunohistochemistry; both are found in cells consistent with type II pneumocytes. SPAR-producing cells resemble the alveolar cells expressing SP-B and SP-C transcripts in appearance, location, and distribution. Therefore, cDNAs for pulmonary SP-A-binding proteins from two disparate species have been isolated and sequenced, and the recombinant proteins they encode bind the same ligand. Further structural, functional, and genetic studies of these proteins may help explain how pulmonary surfactant secretion is regulated. PMID- 8360163 TI - Placement of dinitrophenyl-modified ribosomal proteins in totally reconstituted Escherichia coli 30 S subunits. Localization of proteins S6, S13, S16, and S18 by immune electron microscopy. AB - Purified Escherichia coli ribosomal proteins S6, S13, S16, and S18 were dinitrophenylated at their amino termini and/or at one or more internal lysine residues. Each dinitrophenyl protein was then separately incorporated into reconstituted small ribosomal subunits. Modified proteins were localized on the 30 S subunit surface by electron microscopy of reconstituted subunits complexed with antibodies to dinitrophenol (DNP). DNP protein S13 was placed on the subunit head above the platform and on the surface that faces the large subunit. DNP-S18 was localized to the subunit platform below the tip and in a region associated with binding to 50 S subunits. DNP proteins S6 and S16 were both localized near the junction of the subunit body and platform; DNP-S6 was available to antibody in 70 S ribosomes and was placed on the cytoplasm-facing side of the subunit in an area that overlaps the platform and body of the particle. DNP-S16 in 70 S ribosomes was not bound by antibody. It was localized to the 30 S body near its junction with the platform and on the surface facing the 50 S particle. The results complement and clarify data obtained using other approaches. PMID- 8360164 TI - Mutational study of Streptomyces tyrosinase trans-activator MelC1. MelC1 is likely a chaperone for apotyrosinase. AB - The melanin operon (melC) of Streptomyces antibioticus contains two genes, melC1 and melC2 (apotyrosinase). Our previous studies indicated that MelC1 forms a transient binary complex with the downstream apotyrosinase MelC2 to facilitate the incorporation of copper ion and the secretion of tyrosinase. In this study, we investigated the role of histidine residues in the function of MelC1 by examining a series of substitution or deletion mutants. Of eight mutants only the substitution of His-117 with Asp in the mutant M-117D rendered the complete abolishment of the intracellular tyrosinase activity in both Streptomyces and Escherichia coli. Replacement of His-102 by Leu in the mutant M-102L also caused a 64-70% reduction of tyrosinase activity in Streptomyces and E. coli. These two mutations also affected the secretion of both MelC1 and MelC2 proteins. In vitro copper activation of the purified MelC1.MelC2 binary complex from these two mutants regained only 20-30% tyrosinase activity of the wild type. Biochemical characterization of the tyrosinases from these two mutants revealed that they were different in several aspects. The intracellular tyrosinase activity in M 117D, but not in M-102L, could be partially reactivated by copper ion or by the cell extract containing MelC1. The copper content and the specific activity of the tyrosinase purified from the culture supernatant from M-117D were only 40% of those in wild type and M-102L. Additionally, fast protein liquid chromatography analysis indicated that in these two mutants the copper activation process was defective, very likely due to the incompetent MelC1.MelC2 binary complex formed: reduced association in M-117D and elevated association in M-102L. Furthermore, the conformation of MelC2 in the binary complex or in the mature enzyme form in wild type could be differentiated by the proteinase K digestion pattern, and so did the conformation of MelC2 found in those of M-102L, but not in M-117D mutant. Taken together, our results demonstrate that MelC1 is indispensable in the incorporation of copper ion into MelC2 apotyrosinase via a transient, competent binary complex formation, during which a conformational transition of MelC2 has occurred. This strongly suggests that MelC1 is a chaperone for the apotyrosinase MelC2. PMID- 8360165 TI - PEB1, the major cell-binding factor of Campylobacter jejuni, is a homolog of the binding component in gram-negative nutrient transport systems. AB - The protein PEB1 (28 kDa) is a common antigen and a major cell adherence molecule of Campylobacter jejuni and Campylobacter coli. We created a bank of chromosomal DNA fragments of C. jejuni strain 81-176 using lambda gt11. Screening this bank in Escherichia coli Y1090 cells with antibody raised against purified PEB1 enabled us to isolate and to purify a clone with a 2.6-kilobase insert expressing an immunoreactive protein of 28 kDa. DNA sequencing revealed that the insert contains three complete and two partial open reading frames (ORFs), designated 5' to 3' as ORFs A-E. The peb1A gene (ORF D) contains 780 bases encoding a 259 residue polypeptide having a calculated molecular mass of 28,181 Da. The peptide sequence starting at residue 27 matches that determined from aminoterminal sequencing of mature PEB1 from C. jejuni. The first 26 residues contain typical signal peptidase I and II cleavage sites. The deduced amino acid composition and pI of the recombinant mature protein are similar to those determined for purified PEB1. Gene bank searches indicated significant overall homology of peb1A and ORF C with operons for amino acid transport systems in other Gram-negative organisms. peb1A is homologous to the binding components of systems such as glnH (27.8%) and hisJ (28.9%), whereas ORF C has nearly 50% identity to glnQ and hisP. Thus, PEB1 could be involved both in binding to intestinal cells and in amino acid transport. PMID- 8360166 TI - The amino-terminal 29 amino acids of cytochrome P450 2C1 are sufficient for retention in the endoplasmic reticulum. AB - Cytochromes P450 are inserted into and anchored to the endoplasmic reticulum (ER) membrane by a hydrophobic signal sequence at the NH2 terminus. To determine whether the NH2-terminal sequence might also have an ER retention function, the NH2-terminal 29 amino acids of cytochrome P450 2C1, with and without an additional 29 amino acids containing an N-glycosylation site, were fused either to a soluble cytoplasmic protein, Escherichia coli beta-galactosidase, or to a secreted protein, E. coli alkaline phosphatase, and the hybrid proteins were expressed in COS1 cells. Subcellular fractionation indicated that both the beta galactosidase and alkaline phosphatase hybrid proteins cosedimented with marker enzymes for ER membranes, and localization by immunofluorescent staining was consistent with an ER location. Hybrid proteins with the NH2-terminal glycosylation site were glycosylated in COS1 cells, and the carbohydrate moiety was sensitive to endoglycosidase H digestion, providing further evidence that the proteins were retained in the ER. In vitro studies of membrane insertion of the alkaline phosphatase hybrid indicated that fusion to alkaline phosphatase hybrid indicated that fusion to alkaline phosphatase did not alter the topological properties of the cytochrome P450 NH2-terminal sequence. In addition, alkaline phosphatase fused to the extracellular and transmembrane domains of epidermal growth factor receptor was transported to the plasma membrane in COS1 cells, which establishes that alkaline phosphatase as a cytoplasmic domain does not prevent transport from the ER. These observations indicate that the large cytoplasmic domain of cytochrome P450 is not required for retention in the ER and suggest that a specific sequence or structure within the NH2-terminal 29 amino acids functions as an ER retention signal. PMID- 8360167 TI - Induction of arachidonate 12-lipoxygenase mRNA by epidermal growth factor in A431 cells. AB - 12(S)-Hydroxyeicosatetraenoic acid is biosynthesized from arachidonic acid by the microsomal fraction of human epidermoid carcinoma A431 cells, and the microsomal 12-lipoxygenase activity is enhanced by about 2-fold by epidermal growth factor (EGF) with a 10-h lag period (Chang, W.C., Ning, C.C., Lin, M.T., and Huang, J.D. (1992) J. Biol. Chem. 267, 3657-3666). The microsomal 12-lipoxygenase in A431 cells was only 3% active with linoleic acid as compared with arachidonic acid. The enzyme was immunoprecipitated by a monoclonal antibody against human platelet 12-lipoxygenase but not by that against porcine leukocyte enzyme. A 3.1-kilobase mRNA was detected in A431 cells by Northern blot analyses using cDNA probe of human platelet 12-lipoxygenase. EGF could increase the 12-lipoxygenase mRNA level by about 2-fold with a lag period of 10 h, which was well parallel with the increase in the enzyme activity. The induction of the 12-lipoxygenase mRNA by EGF was completely blocked by 35 microM cycloheximide, if present in culture medium during EGF treatment, indicating that a de novo protein biosynthesis was essential for EGF-induced 12-lipoxygenase mRNA expression. Our data provide the first evidence for the inducibility of human 12-lipoxygenase gene expression by a growth factor. PMID- 8360168 TI - Differential expression of transmembrane proteoglycans in vascular smooth muscle cells. AB - Rat aortic vascular smooth muscle (VSM) cells synthesize the transmembrane proteoglycan syndecan (Cizmeci-Smith, G., Asundi, V., Stahl, R. C., Teichman, L. J., Chernousov, M., Cowan, K., and Carey, D. J. (1992) J. Biol. Chem. 267, 15729 15736). The present work demonstrated that VSM cells synthesize the related transmembrane proteoglycan fibroglycan and that increased expression of these two proteoglycans is stimulated under different conditions. Fibroglycan synthesis by cultured rat aortic VSM cells was demonstrated by Northern blot analysis with a rat fibroglycan cDNA probe and immunoblot analysis with anti-rat fibroglycan antibodies. Effects of growth factors and vasoactive substances on syndecan and fibroglycan expression were examined by Northern blot analysis. Syndecan mRNA levels increased in response to stimulation of VSM cells with serum, platelet derived growth factor, or angiotensin II. VSM cells stimulated with platelet derived growth factor contained more syndecan core protein and processed syndecan than control cells. Fibroglycan mRNA levels either decreased or remained unchanged in response to these agents. Fibroglycan mRNA levels increased following transforming growth factor-beta stimulation, while syndecan mRNA levels decreased. Other agents, including basic fibroblast growth factor, endothelin, and carbacyclin did not alter the expression of either proteoglycan. Syndecan and fibroglycan mRNA levels also varied as a function of cell density. These data demonstrate that syndecan and fibroglycan expression are regulated differently in VSM cells and lend support to the hypothesis that these proteoglycans carry out distinct physiological functions. PMID- 8360169 TI - Purification and characterization of bovine brain platelet-activating factor acetylhydrolase. AB - Platelet-activating factor (PAF) acetylhydrolase, which removes the acetyl moiety at the sn-2 position, has been found in plasma and tissue cytosol. PAF acetylhydrolase in bovine brain cytosol was chromatographically separated into three distinct fractions, all of which exhibited pH optima in the neutral to mild alkaline region and were unaffected by EDTA. We have purified the major fraction of the enzyme to near homogeneity. The purified enzyme had a molecular mass of about 100 kDa, as estimated by gel filtration chromatography, and gave three distinct bands of 45, 30, and 29 kDa, respectively, on sodium dodecyl sulfate polyacrylamide gel electrophoresis. These polypeptides exclusively co-migrated with the activity throughout the purification steps. These data suggest that this set of polypeptides corresponds to the subunits of bovine brain PAF acetylhydrolase. Diisopropyl fluorophosphate completely inhibited the activity at 0.1 mM. [3H]Diisopropyl fluorophosphate labeled only the 29-kDa polypeptide, suggesting that this polypeptide possesses an active serine residue(s). The purified enzyme displayed similar activity against PAF and oxidatively modified phosphatidylcholine, but did not hydrolyze phosphatidylcholine or phosphatidylethanolamine with two long chain acyl groups. Thus, the intracellular PAF acetylhydrolase is likely to be a new member of the calcium-independent phospholipases A2 in mammalian tissues. PMID- 8360170 TI - Characterization of two different glycosylated domains from the insoluble mucin complex of rat small intestine. AB - The highly glycosylated domains of rat small intestinal mucins were isolated after reduction and trypsin digestion and separated into two populations (A and B) by gel chromatography. The molecular mass values were 650 and 335 kDa, respectively, and the relative yields suggest that the two glycopeptides occur in equimolar proportions. Electron microscopy revealed linear structures with weight average lengths of 230 nm (A) and 110 nm (B) corresponding to a mass/unit length of about 3 kDa/nm. The protein cores (17-19%) contain large amounts of threonine (over 40%), serine (17-24%), and proline (18-19%). Carbohydrate and sulfate account for approximately 80 and 0.5%, respectively, and gas chromatography-mass spectrometry showed that the patterns of neutral and sialic acid-containing glycans are very similar in the two glycopeptides. Both contain a significant amount (7-10 mol %) of single GalNAc residues, the average oligosaccharide is about 4 sugar residues long, and the largest species observed are heptasaccharides. The major neutral and sialic acid-containing oligosaccharides are Fuc1-2Gal1-3GalNAcol and GlcNAc1-6(NeuGc2-Gal1-3)GalNAcol, respectively. Sialic acid is present as both N-acetyl- and N-glycoloyl-neuraminic acid. Repeated extractions of the tissue with guanidinium chloride left approximately 80% of the mucus glycoproteins as an insoluble glycoprotein complex whereas exposure to dithiothreitol or high speed homogenization accomplished complete solubilization. The "subunits" obtained after reduction with dithiothreitol are larger than glycopeptides A and B, and fragments corresponding in size to the latter are obtained after cleavage with trypsin. Most of the mucins from rat small intestine thus occurs as an insoluble glycoprotein complex composed of subunits joined with disulfide bonds. The subunits contain two highly glycosylated regions with different lengths substituted with very similar oligosaccharides. PMID- 8360171 TI - Molecular cloning of the gene for bilirubin oxidase from Myrothecium verrucaria and its expression in yeast. AB - Myrothecium verrucaria bilirubin oxidase (EC 1.3.3.5) is an enzyme catalyzing the oxidation of bilirubin to biliverdin and other substrates. We have purified bilirubin oxidase from the medium of M. verrucaria and determined its partial amino acid sequence and isolated cDNA fragment amplified by polymerase chain reaction using oligonucleotide primers designed on the basis of the partial amino acid sequence. The gene for bilirubin oxidase has been cloned from a genomic library using the cDNA fragment as a probe. The gene encodes a precursor of bilirubin oxidase consisting of 572 amino acid residues, which comprises the prepro-region of 38 amino acid residues and the mature enzyme of 534 amino acid residues containing one cysteine. Five introns were found within the coding region. Sequence comparison of bilirubin oxidase with other blue copper proteins (laccase, ascorbate oxidase, human ceruloplasmin, plastocyanin, and azurin) revealed the presence of four domains corresponding to potential copper ligands. We have expressed this bilirubin oxidase gene in Saccharomyces cerevisiae under the repressible acid phosphatase promotor and found an active recombinant bilirubin oxidase, establishing the functional identity of the gene. PMID- 8360172 TI - Evidence that the transcription factor USF is a component of the human beta globin locus control region heteromeric protein complex. AB - The human locus control region (LCR) consists of four DNase I hypersensitive sites upstream of the epsilon-globin gene and is intimately involved in globin gene transcription. We have used DNase I footprinting with K562 erythroleukemia cell extracts to identify protein components of the minimal LCR element, hypersensitive site 2. Six major regions of protection were observed, and the occupation of two regions (sites II and V) was strongly temperature-dependent. Fractionation of K562 nuclear proteins revealed a single major protein that bound tightly to site II. An E-box was necessary for high affinity binding to DNA. We used antibodies and recombinant USF protein to prove that the helix-loop-helix transcription factor USF is the only detectable component in K562 cells that binds to this site. Despite significant differences between site II and a canonical USF-binding site, the USF binding affinity was comparable for the two sites. In both cases the interaction with the E-box of either wild-type USF or a approximately 15-kDa minimal USF DNA binding polypeptide displays an unusual positive temperature dependence, consistent with the observed footprinting behavior. The results show that a relatively ubiquitous factor, not confined to erythroid cells, is an important part of the complex of proteins bound at hypersensitive site 2 of the LCR in K562 cells. PMID- 8360173 TI - Characterization of high and low molecular weight forms of amphiregulin that differ in glycosylation and peptide core length. Evidence that the NH2-terminal region is not critical for bioactivity. AB - Human amphiregulin (AR) is a polypeptide growth regulator which acts by binding to and activating the epidermal growth factor (EGF) receptor tyrosine kinase. AR consists of an EGF-like domain and an NH2-terminal extension which contains potential glycosylation sites and nuclear localization signals. Two high molecular weight species which had molecular masses of approximately 16.5 kDa (HMW-AR1 and HMW-AR2) and a approximately 9.5-kDa low molecular weight form (LMW AR) were isolated from the conditioned medium of phorbol 12-myristate 13-acetate treated MCF-7 human breast carcinoma cells by sequential heparin affinity, immunoaffinity, and reverse phase-high performance liquid chromatography. HMW-AR1 and HMW-AR2 were found to possess complex or hybrid type N-linked oligosaccharide structures that contained sialic acid. Additionally, HMW-AR1 and HMW-AR2 contained the disaccharide, Gal beta(1-->3)GalNAc, linked to Ser/Thr residues. No carbohydrate moieties were detected in LMW-AR. Mapping of the peptide cores of these molecules using antipeptide antibodies revealed that HMW-AR1 and HMW-AR2 were intact molecules, whereas LMW-AR contained the EGF-like domain, but possessed a truncated NH2-terminal extension. LMW-AR, HMW-AR1, and HMW-AR2 were all found to be potent stimulators of DNA synthesis in MCF-10A human mammary epithelial cells. These results suggest that the NH2-terminal region of the AR molecule is not critical to the ability of AR to activate the EGF receptor tyrosine kinase. PMID- 8360174 TI - Yeast bZip proteins mediate pleiotropic drug and metal resistance. AB - Saccharomyces cerevisiae contains a group of transcription factors related to mammalian c-Jun. This yeast Jun-family of proteins consists of GCN4, a regulator of genes involved in amino acid biosynthesis, and yAP-1, a factor conferring pleiotropic drug resistance when overexpressed. In the work described here, we show that a third member of the yeast Jun-family exists. This protein has been designated CAD1 and provides resistance to cadmium when present on a high-copy plasmid. CAD1 and yAP-1 are related in their amino-terminal DNA binding domains and can recognize the same DNA target site in vitro. Overproduction of CAD1 leads to transcriptional activation of an artificial reporter gene in delta yap1 cells. High level production of either CAD1 or yAP-1 causes cells to acquire a pleiotropic drug-resistant phenotype and to be able to tolerate normally toxic levels of iron chelators and zinc. Surprisingly, disruption of the CAD1 gene has no effect on the normal cellular resistance to cadmium but delta yap1 mutants are hypersensitive to this cytotoxic metal. The cadmium hypersensitivity of the delta yap1 mutant described here indicates that one major role of YAP1 in the yeast cell is to mediate resistance to this metal. PMID- 8360175 TI - Specific uptake of retinol-binding protein by variant F9 cell lines. AB - Serum retinol-binding protein (RBP) specifically binds to and is internalized by F9 embryonal carcinoma cells. Monolayers of F9 cells were differentiated into a primitive endoderm stage by addition of retinoic acid. Fluorescein-derivatized or radiolabeled RBP associated with F9 cell monolayers at 37 degrees C in a time- and concentration-dependent manner. Competition by simultaneous incubation with excess unlabeled RBP indicated that this association was specific and saturable; the apparent dissociation constant was 200-300 nM using either tracer. At 37 degrees C, over 80% of the cell-associated RBP was internalized, and only a small fraction was bound to the cell surface; fluorescence microscopy indicated that internalized RBP was in small vesicles within the cytoplasm. Internalized RBP was subsequently degraded and released from the cell in an acid-soluble form. Parental F9 cells were heterogeneous in their ability to associate with RBP. Random subcloning identified natural variant F9 cell lines which did, or did not, express this biological activity upon retinoic acid-induced differentiation. The clonal nature of the capacity for RBP uptake suggests that this specific internalization is a heritable trait. Together, these observations provide strong evidence that RBP uptake occurs by a receptor-mediated process in F9 cells. The cycle of RBP internalization and degradation by F9 cells bearing specific RBP receptors may provide a regulable mechanism for the cellular accumulation of serum retinol. PMID- 8360177 TI - Purification, characterization, and cellular localization of the 100-kDa human placental GTPase-activating protein. AB - Human placenta contains, in addition to the ubiquitous p120-GTPase-activating protein (GAP), another isoform of 100 kDa, which is specific to this organ. We have established a method for purifying this placental p100-GAP to near homogeneity. The purified p100-GAP allowed the preparation of polyclonal and monoclonal anti Ras-GAP antibodies. Two monoclonal antibodies were selected for a two-site enzyme immunoassay. This simple and accurate assay in turn facilitated the detection of the GAPs during purification. The purified p100-GAP has a specific activity identical to and catalytic properties similar to those of native p120-GAP. Sequence analysis of p100-GAP revealed almost total identity to the known corresponding sequences predicted by the cDNA. The purified p100-GAP kept its activity for 1 year when stored at -80 degrees C. Our immunometric assay showed GAP to be present in human placental extracts at the exceptional abundance of about 0.1% of the total protein content. Quantitative assays showed p100-GAP to be up to 10 times more abundant than p120-GAP. Use of our antibodies allowed the specific localization of placental GAPs to cytotrophoblasts and in the syncytiotrophoblast barrier. Hence p100-GAP is shown to be found only in trophoblasts. The large quantity of p100-GAP in trophoblasts suggests that it may play a regulatory role in the proliferation or the differentiation of this cell type. PMID- 8360176 TI - Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels. AB - A novel peptidyl inhibitor of K+ channels has been purified to homogeneity from venom of the new world scorpion Centruroides margaritatus. The primary structure of this 39-amino-acid peptide, which we term margatoxin (MgTX), was determined by amino acid compositional analysis and peptide sequencing. Margatoxin potently inhibits binding of radiolabeled charybdotoxin (ChTX) to voltage-activated channels in brain synaptic plasma membranes. Like ChTX, MgTX blocks the n-type current of human T-lymphocytes (Kv1.3 channel), but compared to ChTX, is 20-fold more potent (half-block at approximately 50 pM), has a slower dissociation rate, and has no effect on calcium-activated channels. To demonstrate that these characteristics are due solely to the purified toxin, recombinant MgTX was expressed in Escherichia coli as part of a fusion protein. After cleavage and folding, purified recombinant MgTX displayed the same properties as native peptide. Replacement of the COOH-terminal histidine residue of MgTX with asparagine resulted in a peptide with a 10-fold reduction in potency. This was due to a faster apparent dissociation rate, suggesting that the COOH-terminal amino acid may play an important role in the binding of MgTX to the Kv1.3 channel. MgTX displays significant sequence homology with previously identified K+ channel inhibitors (e.g. ChTX, iberiotoxin, noxiustoxin, and kaliotoxin). However, given its potency and unique selectivity, MgTX represents an especially useful tool with which to study the physiologic role of Kv1.3 channels. PMID- 8360179 TI - Myristoylation of hippocalcin is linked to its calcium-dependent membrane association properties. AB - Hippocalcin, a recently identified Ca(2+)-binding protein of the recoverin family exclusively expressed in the hippocampus, has a primary structure containing three putative Ca(2+)-binding sites (EF-hands) and a possible NH2-terminal myristoylation site. 45Ca blots demonstrated that every three EF-hand domains, expressed as fusion proteins in Escherichia coli, bind Ca2+, indicating that hippocalcin binds 3 mol of Ca2+/mol of protein. To determine whether hippocalcin is myristoylated, hippocalcin mRNA was translated in vitro in the presence of [3H]myristic acid. 3H label was resistant to hydroxylamine treatment, and replacement of NH2-terminal glycine with alanine prevented 3H label incorporation, indicating that in vitro translated hippocalcin covalently bound [3H]myristic acid at the NH2-terminal glycine. In vitro translated hippocalcin is quantitatively myristoylated, as evidenced by an electrophoretic mobility shift of [35S]methionine-labeled protein on two-dimensional gels. Native hippocalcin comigrated precisely with the in vitro translated hippocalcin on two-dimensional gels, suggesting that native hippocalcin is myristoylated. Native and in vitro translated hippocalcins, but not non-myristoylated mutagenic (Gly1-Ala1) hippocalcin, displayed Ca(2+)-dependent membrane association, indicating that myristoylation participates in its Ca(2+)-dependent membrane association properties. In vitro translated hippocalcin bound to phospholipid vesicles somewhat, however, phospholipid association was insufficient for its membrane association properties, suggesting that the NH2-terminal myristoyl moiety on hippocalcin interacts with lipid bilayers and facilitates interaction with other membrane proteins. PMID- 8360178 TI - Purification of the major histocompatibility complex class I transcription factor H2TF1. The full-length product of the nfkb2 gene. AB - H2TF1 is a ubiquitous major histocompatibility complex (MHC) class I-specific transcription factor, which binds to the palindromic kappa B enhancer site upstream of MHC class I genes. Here we report that H2TF1 consists of a polypeptide with relative molecular mass 110,000, that corresponds to the predicted 100-kDa product (NF-kappa B2 p100) encoded by the candidate proto oncogene nfkb2 (lyt-10). H2TF1 was purified by a novel affinity chromatography method and identified as the NF-kappa B2 p100 polypeptide by peptide sequencing as well as by reactivity with a specific antiserum. Purified H2TF1 binds the MHC kappa B site with high affinity (KD = 3 x 10(-11) M), in contrast with previous reports that NF-kappa B2 p100 did not bind DNA. PMID- 8360181 TI - The extracellular matrix proteins laminin and fibronectin contain binding domains for human plasminogen and tissue plasminogen activator. AB - This study describes the binding of plasminogen and tissue-type plasminogen activator (t-PA) to the extracellular matrix proteins fibronectin and laminin. Plasminogen bound specifically and saturably to both fibronectin and laminin immobilized on microtiter wells, with Kd(app) values of 115 and 18 nM, respectively. Limited proteolysis by endoproteinase V8 coupled with ligand blotting analysis showed that both plasminogen and t-PA preferentially bind to a 55-kDa fibronectin fragment and a 38-kDa laminin fragment. Amino acid sequence analysis demonstrated that the 5-kDa fragment originates with the fibronectin amino terminus whereas the laminin fragment was derived from the carboxyl terminal globular domain of the laminin A chain. Ligand blotting experiments using isolated plasminogen domains were also used to identify distinct regions of the plasminogen molecule involved in fibronectin and laminin binding. Solution phase fibronectin binding to immobilized plasminogen was mediated primarily via lysine binding site-dependent interactions with plasminogen kringles 1-4. Lysine binding site-dependent binding of soluble laminin to immobilized plasminogen kringles 1-5 as well as an additional lysine binding site-independent interaction between mini-plasminogen and the 38-kDa laminin A chain fragment were also observed. These studies demonstrate binding of plasminogen and tissue-type plasminogen activator to specific regions of the extracellular matrix glycoproteins laminin and fibronectin and provide further insight into the mechanism of regulation of plasminogen activation by components of the extracellular matrix. PMID- 8360180 TI - The PSI-K subunit of photosystem I from barley (Hordeum vulgare L.). Evidence for a gene duplication of an ancestral PSI-G/K gene. AB - Photosystem I of barley contains a polypeptide with an apparent molecular mass of 7 kDa when isolated using the detergent n-decyl-beta-D-maltopyranoside. The 7-kDa polypeptide is lost from the PS I complex isolated using Triton X-100. The 7-kDa polypeptide and a corresponding full-length cDNA clone have been isolated. Based on high sequence similarity to an N-terminal sequence of PSI-K from spinach and to the deduced amino acid sequence of Psak from Chlamydomonas reinhardtii the 7 kDa barley polypeptide is identified as PSI-K. The cDNA clone encodes a precursor polypeptide of 131 amino acid residues with a calculated molecular mass of 13,726 Da. The transit peptide shows characteristics of polypeptides imported into the chloroplast. PSI-K has two hydrophobic regions predicted to be membrane-spanning alpha-helices. In vitro expressed prePSI-K polypeptide was imported into intact chloroplasts, whereas an in vitro expressed prePSI-K lacking 7 amino acid residues (Met-Ala-Ser-Gln-Leu-Ser-Ala) at the N-terminal end of the transit peptide failed to be imported. The mRNA encoding PSI-K increases during illumination. PsaK is located in a single locus in the genome. PSI-K has significant similarity to PSI-G. When comparing the barley PSI-K and PSI-G with the reported PSI-K sequence from Synechococcus vulcanus, the degree of similarity is equal, suggesting that an ancestral gene has been duplicated in a chloroplast progenitor but not in a cyanobacterial. PMID- 8360182 TI - Modulation of tissue plasminogen activator-catalyzed plasminogen activation by synthetic peptides derived from the amino-terminal heparin binding domain of fibronectin. AB - Fibronectin is a multidomain adhesive glycoprotein found in plasma, interstitial connective tissue, and basement membrane. Diverse biological activities have been associated with the fibronectin molecule including cell adhesion, cell migration, wound healing, hemostasis, and oncogenic transformation. Binding sites for heparin, fibrin, gelatin/collagen, and cells have been localized to various structural domains of the molecule. In addition, fibronectin also binds both plasminogen and tissue plasminogen activator (t-PA) via a 55-kDa amino-terminal fragment (Moser, T.L., Enghild, J.J., Pizzo, S.V., and Stack, M.S. (1993) J. Biol. Chem. 268, 18917-18923). Although intact fibronectin does not enhance the rate of t-PA-catalyzed plasminogen activation, a mixture of proteolytically degraded fibronectin fragments stimulates the activation reaction, resulting in an 11-fold increase in the kcat/Km. Based on these observations, we have synthesized a variety of peptides derived from the plasminogen/t-PA binding region of fibronectin and determined the effect of these peptides on the initial rate kinetics of plasminogen activation by t-PA as well as on plasmin and t-PA amidolytic activity. Here we report that a specific octapeptide, SRNRCNDQ-NH2, consisting of residues 196-203 of the fibronectin molecule is a potent stimulator of t-PA-catalyzed plasminogen activation, resulting in a 15-fold increase in the kcat/Km of the activation reaction. PMID- 8360183 TI - Characterization of the bifunctional cytochrome c reductase-processing peptidase complex from potato mitochondria. AB - In potato, cytochrome c reductase, a protein complex of the respiratory chain, exhibits processing activity toward mitochondrial precursor proteins. One of the two cooperating components of the processing peptidase was shown to be identical with subunit III of the complex. Here we report that two additional proteins of the complex (subunit I and II) share 40-50% sequence identity with the processing enhancing protein, the other component of the processing enzyme from fungi and mammals. Thus the composition and structure of the complex integrated processing peptidase seems to be different from its fungal and mammalian counterparts. Cytochrome c reductase from potato is extraordinarily stable, and separation of subunit III from the complex leads to aggregation of the remaining subcomplex and irreversible loss of processing activity. Expression of the three high molecular weight subunits of the complex allowed purification of each individual protein. Neither the individual subunits nor their combinations are active in in vitro processing assays suggesting that they may need the structural support of the complex for activity. In contrast to mitochondrial processing peptidases from other organisms, the purified potato enzyme is active in the presence of high salt (above 1 M NaCl) and works efficiently without addition of metal ions. These data indicate that potato cytochrome c reductase is a bifunctional protein complex with unique features. Possibly, there is a more general evolutionary relationship between cytochrome c reductases and mitochondrial processing peptidases than hitherto assumed. PMID- 8360184 TI - Purification, cloning, and expression of a bovine UDP-GalNAc: polypeptide N acetyl-galactosaminyltransferase. AB - Partial amino acid sequence was obtained from UDP-GalNAc:polypeptide N acetylgalactosaminyltransferase (polypeptide GalNAc transferase) purified from bovine colostrum. Oligonucleotide primers designed from these sequences were used to amplify and clone a polypeptide GalNAc transferase cDNA from bovine placental mRNA. The cDNA encodes an open reading frame, which is 519 amino acids in length and contains the predicted N-terminal and internal amino acid sequence derived from three Lys-C peptides obtained from the purified protein. There was no sequence homology with the UDP-GalNAc: Fuc alpha 1,2Gal alpha 1,3GalNAc transferase. To verify the authenticity of the clone, the cDNA was cloned in frame with an insulin secretion sequence and was expressed transiently in COS-7 cells. Polypeptide GalNAc transferase activity was detected in the culture medium; no activity was detected in the media of mock-transfected cells. Previous studies have shown that the polypeptide GalNAc transferase from bovine colostrum glycosylates threonine residues more efficiently than serine residues in the same peptide context (O'Connell, B. C., Hagen, F. K., and Tabak, L. A. (1992) J. Biol. Chem. 267, 25010-25018). We found that the cloned polypeptide GalNAc transferase glycosylates the threonine-containing peptide, PPDAATAAPLR, at a 58-fold greater rate than the serine-containing homologue, PPDAASAAPLR. The ratio of the in vitro threonine and serine glycosylation rate is identical for the cloned placental and purified colostral enzymes. It is not known if the preference for threonine over serine is merely context-dependent on the specific amino acids that flank the glycosylation site or if there are discrete threonine- and serine-specific isoforms of this transferase. Alternatively, there may be additional factors required to enhance the glycosylation of serine residues in vivo. PMID- 8360186 TI - Purification and properties of NADPH-dependent tylosin reductase from Streptomyces fradiae. AB - A reductase of Streptomyces fradiae was speculated to catalyze reduction of tylosin to relomycin, an industrially undesirable product. The activity of tylosin reductase was closely related to bacterial growth, suggesting involvement of the enzyme in a primary metabolism. The reductase activity was improved significantly in vivo and in vitro. The enzyme was also partially stabilized in vitro. Using a simple five-step chromatographic procedure, the reductase was purified 480-fold to apparent homogeneity. The purified reductase had a molecular mass of 270 kDa and consisted of two different subunits of 26 and 7 kDa at 1:1 ratio. The enzyme exhibited an absorption maximum at 405 nm and was inhibited by exogenous FAD or FMN, indicating a flavin as its prosthetic group. Tylosin reductase was optimally active at pH 7.0-7.2 and 40 degrees C with NADPH as a preferred electron donor. The Km of the enzyme for tylosin was 1.4 mM and that for NADPH was 0.15 mM. The Vmax for the enzymatic reaction was 917 mumol of tylosin formed/min/mg protein. The enzymatic conversion of tylosin to relomycin was coupled to that of NADPH to NADP+ at a stoichiometric ratio of 1:1. Tylosin reductase showed a broad substrate specificity toward all macrolide aldehydes (as normal and shunt metabolites of tylosin biosynthesis) tested. Thus, the enzyme may have a physiological role of macrolide detoxification for the bacterium. PMID- 8360185 TI - Protease nexin-1, a thrombin inhibitor, is regulated by interleukin-1 and dexamethasone in normal human fibroblasts. AB - Thrombin participates in several regulatory events following injury as a result of its effects on blood coagulation and cell migration, proliferation, and differentiation. Protease nexin-1 (PN-1) is a potent thrombin inhibitor in the extracellular environment. Since injury-related factors are known to regulate the synthesis and secretion of PN-1, the inhibitor may serve to modulate the actions of thrombin during injury. Here we report the molecular mechanisms that underlie this regulation. In normal human fibroblasts, interleukin-1 (IL-1) beta stimulated the synthesis and secretion of PN-1. The stimulation correlated with an increase in steady-state levels of PN-1 mRNA. Treatment of cells with both cycloheximide and IL-1 reduced the levels of PN-1 mRNA. Nuclear run-on assays indicated that IL-1 modestly increased the rate of PN-1 transcription. However, experiments with actinomycin D demonstrated that IL-1 significantly increased the half-life of the PN-1 mRNA. In contrast, dexamethasone (DXM) repressed the synthesis and secretion of PN-1 from fibroblasts. This effect correlated with a decrease in PN-1 mRNA. A sustained decrease in PN-1 mRNA was also seen when cells were treated with cycloheximide and DXM. In nuclear run-on assays, DXM functioned as a transcriptional repressor of PN-1 synthesis. Treatment of cells with actinomycin D showed that DXM did not affect mRNA stability. Thus, our experiments demonstrate that IL-1 and DXM, which function biologically in different fashions, regulate the synthesis of PN-1 by separate molecular mechanisms. While DXM directly regulates PN-1 at the level of transcription, IL-1 in the presence of ongoing protein synthesis regulates PN-1 production predominantly in a post-transcriptional fashion by increasing the half-life of the PN-1 mRNA. PMID- 8360187 TI - Steroid requirement for androgen receptor dimerization and DNA binding. Modulation by intramolecular interactions between the NH2-terminal and steroid binding domains. AB - Infection of Spodoptera frugiperda Sf9 insect cells with recombinant human androgen receptor (AR) baculovirus results in expression of a 118-kDa phosphoprotein that displays high affinity androgen binding and androgen dependent targeting to the nucleus. Using the DNA mobility shift assay, specific in vitro binding of full-length AR to androgen response element DNA (ARE) requires intracellular hormone exposure. The ability of a variety of steroids to induce ARE binding paralleled their transcriptional potential. Certain antihormones, cyproterone acetate and RU486, promote ARE binding, but a pure antiandrogen, hydroxyflutamide, inhibits AR binding to ARE DNA. AR dimerization requires incubation of recombinant baculovirus-infected insect cells with androgen, but only when one or both components of the dimer contain the NH2 terminal domain. Based on the intensities of ARE binding and lack of binding to an ARE half-site, it appears that, unlike the glucocorticoid receptor, AR binds DNA primarily as a dimer. Thus, full-length baculovirus-expressed AR requires intracellular hormone exposure for dimerization and ARE binding to overcome inhibition imposed by the AR NH2-terminal domain. Antihormones with agonist activity promote dimerization and ARE binding, while a pure antiandrogen blocks AR DNA binding. It is concluded that intramolecular interactions between the NH2 terminal and steroid-binding domains are regulated by the specificity of hormone binding and modulate receptor dimerization and DNA binding. PMID- 8360188 TI - A new isoform of the laminin receptor integrin alpha 7 beta 1 is developmentally regulated in skeletal muscle. AB - Within the integrin family, there are two groups of receptors that bind laminin. One of these groups comprises the heterodimers alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1, all of which bind the E8 fragment of laminin, and whose alpha subunits show significant homology at the amino acid sequence level. alpha 3 and alpha 6 exist as isoforms with distinct cytoplasmic domains (termed A and B), suggesting that they may couple laminin adhesion to distinct cellular responses. We report the identification of a new alpha 7 mRNA which encodes an alpha 7 protein isoform with an alternative cytoplasmic domain. Based on homology with alpha 3 and alpha 6 isoforms, this new isoform is classified as alpha 7A and the previously published one as alpha 7B. This result extends the similarity between alpha 3, alpha 6, and alpha 7 laminin receptor subunits and suggests a common ancestral gene. The alpha 7 beta 1 laminin receptor was proposed to be involved in myogenic differentiation. However, alpha 7 isoforms were not investigated in that context. We detected the alpha 7B isoform mRNA in all tissues and cell types tested, including myocardial and skeletal muscle. In contrast, the alpha 7A isoform was detectable exclusively in skeletal muscle, not in myocardial muscle or cells or any other tissues or cell lines tested. Furthermore, the differentiating skeletal muscle cell line C2C12 expressed only alpha 7B at the replicating myoblast stage and acquired alpha 7A expression upon induction of differentiation and fusion. Splicing of alpha 7B mRNA in C2C12 occurred shortly after myogenin expression and could be an indicator of progression through the program of skeletal muscle differentiation. PMID- 8360189 TI - Functional characterization of the alternatively spliced, placental human growth hormone receptor. AB - The human growth hormone family of peptide hormones is encoded by five genes, pituitary growth hormone (hGH-N), and four placentally expressed genes, growth hormone variant (hGH-V), chorionic somatomammotropin A and B (hCS-A, hCS-B), and prolactin (hPrl). As part of an effort to define the local effects of the placentally expressed members of the GH/Prl family of hormones on the placenta, we have identified an isoform (hGHRd3) of the growth hormone receptor expressed in the placental villi. hGHRd3 mRNA differs from the liver GHR mRNA by the deletion of a 66-base pair segment encoding exon 3. In this study we show that hGHRd3 mRNA encodes a stable and functional receptor. hGHRd3 mRNA is efficiently translated and processed in a rabbit reticulocyte lysate translation system as well as in an in vivo Xenopus laevis oocyte expression system. In Xenopus oocytes hGHRd3 is stably integrated into the cell membrane and binds and internalizes ligand as efficiently as hGHR. hGHRd3 binds all three of the placentally expressed members of the GH/Prl gene family (hGH-V, hCS, and Prl) as well as both the 22 and 20 kDa isoforms of the pituitary hGH-N. The results of the present study strongly support the expression of a functional hGHRd3 isoreceptor in the placenta which may serve in autocrine, paracrine, and/or endocrine activation. PMID- 8360190 TI - Peculiar spectroscopic and kinetic properties of Cys-47 in human placental glutathione transferase. Evidence for an atypical thiolate ion pair near the active site. AB - Cys-47, the most reactive cysteine in the homodimeric glutathione transferase (EC 2.5.1.18) from human placenta (class Pi), displays peculiar acid base and spectroscopic properties. The thiolate form of this residue is characterized by a sharp UV absorption spectrum centered at 229 nm with an epsilon = 7,500 M-1 cm-1. The dependence of the apparent extinction coefficient on pH indicates that the sulfhydryl group of Cys-47 has a pKa value of 4.2. Moreover the dependence of the reactivity of Cys-47 toward bromopyruvate and iodoacetamide with pH resembles that found for the functional sulfhydryls of thiol proteases, which have very low pKa values and exist mainly as a mercaptide-imidazole ion pair. The apparent pKa value for Cys-47, calculated by this kinetic approach, is in good agreement with that determined spectroscopically. X-ray crystallographic data indicate that the protonated amino group of Lys-54, 4.9 A from the sulfur atom, is probably involved in the deprotonation of Cys-47. Calculation of the electrostatic potential on the sulfur atom of Cys-47 gives a theoretical pKa value of 3.5 for the sulfhydryl group. The simulated neutralization of Lys-54 shifts the pKa value of Cys-47 to a normal value of 9.5. These findings suggest that at physiological pH values, Cys-47 exists as the thiolate ion stabilized by an ion pair formation with the protonated amino group of Lys-54, and this probably accounts for its high reactivity. PMID- 8360191 TI - Structure of the alpha subunit of F1-ATPase probed by limited proteolysis. AB - The structure of the isolated alpha subunit of F1-ATPase from the thermophilic Bacillus strain PS3 was probed using limited proteolysis by four different proteases, and the following results were obtained. 1) Distribution of 21 protease-cleaved sites is similar to that of the beta subunit of F1-ATPase (Tozawa, K., Odaka, M., Date, T., and Yoshida, M. (1992) J. Biol. Chem. 267, 16484-16490), thus providing experimental evidence for similar folding topology of the two subunits, and the locations of 11 water-exposed loop regions in the tertiary structure are predicted. 2) Most proteolytic peptides remain associated to maintain the gross structure of the alpha subunit and can reassociate each other after denaturing urea treatment. 3) However, the carboxyl-terminal peptides comprising approximately 80 residues (C1 peptides) are released from other peptide(s) during proteolysis, and those comprising approximately 105 residues (C2 peptides) are released during native polyacrylamide gel electrophoresis after proteolysis. 4) Inclusion of Mg-ATP in the native electrophoretic system prevents the release of the C2 peptide. Addition of Mg-ATP to the proteolysis mixtures results in an increase of the C2 peptide population and a decrease of the C1 peptide population. Thus, Mg-ATP induces a conformational change at the regions of C1 and C2 peptides of the alpha subunit. 5) Except for the trypsin-treated one, protease-treated alpha subunits are reconstitutable with the native beta subunit into the form of alpha 3 beta 3 complexes, which show significantly higher ATPase activities than the intact alpha 3 beta 3 complex. This activation is attributable to the cleavage of a peptide bond that produces C2 peptides. The carboxyl-terminal region of the alpha subunit is likely to be involved in the regulation of ATPase activity in F1-ATPase. PMID- 8360192 TI - Alteration of the structural properties of starch components by the lack of an isoform of starch branching enzyme in rice seeds. AB - This study describes the effect of starch-synthesizing enzymes on biosynthesis of storage starch in rice amylose-extender mutants, which contain branched D-glucans with abnormal structures. Western blot analysis indicated that two out of five amylose-extender mutant lines lacked an isoform of starch branching enzyme, termed RBE3, although the levels of granule-bound starch synthase and a major form of branching enzyme, RBE1, were normal in these two mutants. Proteins corresponding to the 87-kDa RBE3 molecule were present in the three other amylose extender mutants as well as in the wild type. However, the level of branching enzyme activity significantly decreased in all amylose-extender mutants, suggesting that the 87-kDa proteins in these three mutants are inactive forms of RBE3. Therefore, we conclude that formation of the abnormal branched glucans in the amylose-extender mutant of rice is due to the lack of the RBE3 activity. The cDNA clones encoding RBE3 have been identified from a normal rice seed cDNA library in lambda gt11, using a synthetic oligonucleotide as a probe. The deduced amino acid sequence of RBE3 indicates that this protein is initially synthesized as a precursor of 825 amino acids, including a 65-residue transit peptide at the NH2 terminus. The sequences of the catalytic regions in amylolytic enzymes are highly conserved in the sequence of RBE3. Thus, the branching enzyme isoform belongs to a family of the amylolytic enzymes. RBE3 also shares a noticeable degree of sequence identity with RBE1, especially at the central portion of the protein molecule. However, RBE3 possesses an approximately 70-residue extra sequence at the NH2 terminus and lacks a COOH-terminal sequence of almost 50 residues as compared with RBE1. The structural differences at both termini may explain the distinct role in starch synthesis for RBE1 and RBE3. PMID- 8360193 TI - The glucose transporter GluT4 and secretory carrier membrane proteins (SCAMPs) colocalize in rat adipocytes and partially segregate during insulin stimulation. AB - Secretory carrier membrane proteins (SCAMPs) mark the recycling system for the insulin-responsive glucose transporter, GluT4, in rat adipocytes. Anti-GluT4 and anti-SCAMP antibodies each immunoadsorbed vesicles containing both antigens from a low density microsomal fraction that is enriched in both antigens. The immunoadsorbed vesicles also contain VAMPs (synaptobrevins), synaptic vesicle membrane proteins. All three antigens were colocalized in low density microsomal vesicles from both basal and insulin-stimulated adipocytes. The SCAMPs have the same electrophoretic mobility as a major polypeptides detected in GluT4 vesicles. During insulin stimulation, 40% each of GluT4 and VAMPs redistribute from low density microsomes to the plasma membrane fraction; however, < 10% of the SCAMPs redistribute. Immunocytochemical staining of adipose tissue shows almost complete coincidence of SCAMPs and GluT4 in the basal state and extensive redistribution of both antigens to the cell periphery during insulin stimulation. Segregation of antigens during stimulation is not as distinct as observed by fractionation, although there are regions at the cell border where the SCAMPs appear more concentrated than GluT4. These data suggest that during insulin stimulation, in contrast to the behaviour of GluT4, SCAMPs remain tightly associated with the recycling system. PMID- 8360194 TI - Polyamine and polyamine analog regulation of spermidine/spermine N1 acetyltransferase in MALME-3M human melanoma cells. AB - In MALME-3M human melanoma cells the polyamine analog N1,N12-bis(ethyl)spermine (BESPM) suppresses the key polyamine biosynthetic enzymes, ornithine and S adenosylmethionine decarboxylase, and increases the polyamine catabolizing enzyme, spermidine/spermine N1-acetyl-transferase (SSAT) by more than 200-fold. In the present study increases in SSAT activity in MALME-3M cells treated with 10 microM BESPM were found to be accompanied by a substantial (up to 45-fold) accumulation of SSAT mRNA. By Northern blot analysis three RNA transcripts were found to hybridize with the coding region of human SSAT cDNA: a minor high molecular weight (approximately 3.5 kilobases) species designated form A and two lower molecular weight species designated forms B and C (approximately 1.5 and approximately 1.3 kilobases, respectively). Form A increased uniformly during BESPM treatment and was most obvious in nuclear RNA preparations. On the basis of size similarity to the transcribing region of the gene and hybridization with the coding region of SSAT cDNA and its prevalence in nuclear mRNA preparations, form A is thought to represent precursor SSAT RNA. Form C is present in control cells and increases steadily during treatment, whereas form B increases transiently during early treatment (1-3 h). By RNase H digestion assay, form B was found to have a 200-base pair longer poly(A) tract and as such may represent a precursor to form C. Accumulation of SSAT mRNA was found to be a result of increased gene transcription and stabilization of SSAT mRNA. Nuclear run-on studies indicated a 2-4-fold increase in the transcription rate of the SSAT gene. As indicated by actinomycin D studies, the SSAT mRNA half-life increased with BESPM treatment from 17 to 64 h. The natural polyamine, spermine, also increased SSAT mRNA (5.5 fold at 24 h) and behaved similarly to BESPM in inducing the appearance of the same three transcript forms. The polyamine was much less effective than the analog at increasing enzyme activity. Lowering intracellular polyamine pools with inhibitors of biosynthesis decreased basal SSAT mRNA levels by at least 70% indicating, that the gene can be down-regulated as well as up-regulated by polyamines. These findings indicate that SSAT represents a unique example of gene expression being positively influenced at the RNA level by polyamines and their analogs. PMID- 8360195 TI - Cloning and characterization of an endothelin-3 specific receptor (ETC receptor) from Xenopus laevis dermal melanophores. AB - We report here the presence of a receptor specific for endothelin-3 (termed ETc receptor or ETcR) on Xenopus laevis dermal melanophores. Activation of ETcR causes the dispersion of the pigment granules within the melanophores. The EC50 for ET-3 to induce the pigment dispersion is 24 +/- 7 nM, compared to greater than 10 microM for both ET-1 and -2. This effect desensitizes in a manner that is dependent on both time and the concentration of ET-3 used to stimulate the cells. A cDNA encoding for ETcR was isolated by a polymerase chain reaction-mediated DNA amplification strategy using degenerate oligonucleotides prepared based on conserved regions of other known G-protein-coupled receptor sequences and by the subsequent screening of a frog melanophore cDNA library. The cloned cDNA consists of 2,240 nucleotides, with an open reading frame coding for 444 amino acids containing an initial 20-amino acid signal sequence. The predicted mature peptide consists of 424 amino acids with a heptahelical structure common to the G-protein coupled receptor surperfamily. Its deduced amino acid sequence is 47 and 52% identical to ETA and ETB receptors, respectively, while ETA and ETB are 48% identical to each other. Expression of cDNA in HeLa cells, which do not contain endothelin receptors, enables the cells to specifically bind [125I]ET-3. Competition binding experiments performed on HeLa cells transiently expressing pETc show that the apparent Ki values for ET-3 and ET-1 to displace [125I]ET-3 are 45.5 +/- 16 and 114 +/- 22 nM, respectively. PMID- 8360196 TI - Serine 1002 is a site of in vivo and in vitro phosphorylation of the epidermal growth factor receptor. AB - We have shown previously that treatment of A431 cells with epidermal growth factor (EGF) induces desensitization of the EGF receptor. We now show that this desensitization is associated with an increase in the phosphorylation of the receptor on Ser-1002. Using a synthetic peptide corresponding to the sequence surrounding Ser-1002, p34cdc2 was identified as a kinase capable of phosphorylating this serine residue. Purified Xenopus p34cdc2 was found to phosphorylate the synthetic peptide on the serine residue corresponding to Ser 1002. This kinase also phosphorylated purified EGF receptor in vitro on Ser-1002. Phosphorylation of the EGF receptor by p34cdc2 was associated with a decrease in its tyrosine protein kinase activity. These data indicate that the EGF receptor may be a target for phosphorylation by a cyclin-dependent kinase in vivo and imply that receptor function may be regulated in a cell cycle-dependent fashion. PMID- 8360197 TI - Localization of "non-extractable" acetylcholinesterase to the vertebrate neuromuscular junction. AB - Asymmetric forms of acetylcholinesterase (AChE) are thought to be the predominant forms of this enzyme at vertebrate neuromuscular junctions where they attach to the synaptic basal lamina via a collagen-like tail. High salt and heparin containing buffers are capable of solubilizing asymmetric AChE molecules from skeletal muscle; however, detachment of AChE specifically from synaptic basal lamina using these procedures has not been demonstrated. To determine whether AChE can be solubilized from mature neuromuscular junctions, adult quail muscle fibers were extracted with buffered detergent solutions containing either 0.05 M NaCl, 1 m NaCl, 0.5-2 mg/ml heparin, 8 M urea, or 4 m guanidine HCl, and the remaining AChE molecules were localized by indirect immunofluorescence. Analysis of extracted AChE oligomeric forms showed that low salt buffers containing heparin and high salt buffers were capable of solubilizing substantial amounts of catalytically active collagen-tailed AChE, whereas none of these buffers were capable of detaching AChE from synaptic basal lamina. In contrast, digestion with purified collagenase detached asymmetric forms from the non-extractable fraction and removed the AChE from the neuromuscular junctions. Parallel experiments using rat gastrocnemius muscle and enzyme histochemistry to detect AChE gave similar results. These studies indicate that the junctional AChE molecules are firmly attached to the extracellular matrix and that all the conventional extraction buffers used to solubilize the asymmetric collagen-tailed forms of AChE are incapable of detaching this enzyme from the synaptic basal lamina. PMID- 8360198 TI - The blood compatibility catastrophe. PMID- 8360199 TI - Organoapatites: materials for artificial bone. II. Hardening reactions and properties. AB - This article reports on chemical reactions and the properties they generated in artificial bone materials termed "organoapatites." These materials are synthesized using methodology we reported in the previous article of this series. Two different processes were studied here for the transition from organoapatite particles to implants suitable for the restoration of the skeletal system. One process involved the hardening of powder compacts by beams of blue light derived from a lamp or a laser and the other involved pressure-induced interdiffusion of polymers. In both cases, the hardening reaction involved the formation of a polyion complex between two polyelectrolytes. In the photo-induced reaction an anionic electrolyte polymerizes to form the coulombic network and in the pressure induced one, pressure forms the complex by interdiffusion of two polyions. Model reactions were studied using various polycations. Based on these results the organoapatite selected for the study was that containing dispersed poly(L-lysine) and sodium acrylate as the anionic monomer. The organomineral particles can be pressed at room temperature into objects of great physical integrity and hydrolytic stability relative to anorganic controls. The remarkable fact about these objects is that intimate molecular dispersion of only 2-3% by weight organic material provides integrity to the mineral network in an aqueous medium and also doubles its tensile strength. This integrity is essentially nonexistent in "anorganic" samples prepared by the same methodology used in organoapatite synthesis. The improvement in properties was most effectively produced by molecular bridges formed by photopolymerization. The photopolymerization leads to the "hardening" of pellets prepared by pressing of organoapatite powders. The reaction was found to be more facile in the microstructure of the organomineral, and it is potentially useful in the surgical application of organoapatites as artificial bone. PMID- 8360200 TI - Organoapatites: materials for artificial bone. III. Biological testing. AB - This article reports on the in vivo testing of new artificial bone materials we have termed "organoapatites." These materials consist of mineral networks in which organic polymers are intimately dispersed by nucleation and growth of apatite crystals from a mother liquor containing the organic substances. Organoapatites were tested as implants in adult canine cortical bone for periods in the range from 12-35 weeks and fluorochromes were used in the model to investigate the kinetics of bone growth or repair. The analysis of histological samples was carried out using histomorphometric methods as well as fluorescence microscopy. Results showed excellent apposition of poly(amino acid) organoapatites with mineralized bone and fibrous encapsulation when a synthetic polyelectrolyte was the only organic component. This observation suggests that the molecularly dispersed organic dopant amounting to only 2-3% by weight of the microstructure can play a critical role in the tissue response to the implant. Relative to apatite controls, organoapatites were also found to have greater resistance to fragmentation in vivo and those containing amino acid units revealed interfacial bioerosion accompanied by regeneration of mineralized tissue. Design of organoapatite compositions and microstructures may therefore be useful in achieving the specific rate of biological response which is clinically desired. PMID- 8360201 TI - Collagen fibers as a temporary scaffold for replacement of ACL in goats. AB - ACL substitutes made of braided or plied purified collagen fibers and cross linked with hexamethylenediisocyanate were implanted into a total of 14 adult goats to achieve resorption within 8 to 10 months. Two types of collagen fiber prostheses differing in degree of collagen purification were tested. The implants were harvested 2 to 11 months postimplantation, tested for mechanical strength, and evaluated by morphological methods. In the first group (n = 5), the less purified and less cross-linked collagen fiber ACL implant induced fast connective tissue ingrowth. At 6 months postimplantation, 40 to 60% of the collagen implant was resorbed. No studies on breaking strength were done in this group. In the second group, highly purified and more crosslinked ACL implants were less infiltrated by cells and were resorbed only by 10 to 20%. Still, the breaking strength was decreased to 10% of the original implant strength. In the second group, the fixation of the ACL implant in the bone tunnel with a bone wedge was insufficient (n = 6); however, additional fixation with metal screws was successful (n = 3). We conclude that cross-linked collagen fibers alone cannot be used as a safe ACL substitute as they quickly lose mechanical strength despite limited biodegradation. PMID- 8360202 TI - Variations between Biomer lots. 2: The effect of differences between lots on in vitro enzymatic and oxidative degradation of a commercial polyurethane. AB - In vitro degradation of two lots of Biomer, a commercial poly(ether urethane urea), has been investigated in order to understand possible mechanisms for in vivo degradation. Two lots of Biomer, BSUA001 and BSP067, were used in the study. Lot BSUA001 contained a poly(diisopropylaminoethyl-methacrylate), an ultraviolet stabilizing additive. This additive was absent in lot BSP067. Samples of each lot were exposed to two hydrolytic enzymes, papain and leucine aminopeptidase, and to hydrogen peroxide for 24 h. The extent of degradation was assessed using high pressure gel permeation chromatography and x-ray photoelectron spectroscopy (XPS). Statistically significant changes in the molecular-weight distribution occurred in lot BSP067 for all three treatments. Only the hydrogen peroxide treatment resulted in statistically significant changes in the molecular weight of lot BSUA001. XPS data for samples of lot BSUA001 that had been treated with hydrogen peroxide revealed the formation of nitroso groups and protonated amines at the surface. The data suggest that surface chemistry is important for enzyme catalyzed degradation, while permeability is important for degradation by hydrogen peroxide. PMID- 8360203 TI - Platelet deposition onto polymeric surfaces during shunting. AB - In an attempt to develop blood-contacting tubes that can be applied for short term uses with a reduced heparin concentration or, ideally, without heparinization, we evaluated the blood compatibility of polymeric materials with a rabbit ex vivo shunt model. The shunt tubes employed were made of silicone, plasticized poly(vinyl chloride) (PVC), and segmented poly(ether urethane) (PU). In addition, two kinds of surface-modified tube were used: poly(vinyl alcohol) (PVA)-coated PVC and poly(dimethylacrylamide) (PDMAA)-grafted PU. The ex vivo shunt results correlated well with protein adsorption and platelet adhesion in vitro. The following order for the extent of platelet deposition was given, irrespective of the blood-contacting duration: PDMAA-grafted PU < PVA-coated PVC < PU < silicone, PVC. It is likely that many platelet aggregates detached from the PVA-coated PVC surface. For PDMAA-grafted PU, no trace of detachment of aggregates could be detected on any of the SEM photographs. The number and morphology of blood cells adhered onto the tube surfaces during ex vivo shunting were dependent on the kind of polymer surfaces, the blood exposure time, and the flow rate of blood. PMID- 8360204 TI - Degradation of medical-grade polyurethane elastomers: the effect of hydrogen peroxide in vitro. AB - Treatment of Pellethane 2363-80A--a medical-grade poly(tetramethylene oxide) based polyurethane elastomer--with 25% (w/w) hydrogen peroxide at 100 degrees C for times ranging from 24 h to 336 h led to significant decreases in ultimate tensile properties and decreases in molecular weight, both at the surface and in the bulk. IR spectral changes were similar to those observed after degradation in vivo. Differential scanning calorimetry showed that hydrogen-peroxide-induced degradation was associated with greater order in the hard domain and greater mobility in the soft domain. Studies conducted with low-molecular-weight model compounds for the hard and soft segments confirmed that methylene groups adjacent to oxygen were susceptible toward oxidation. The extent of degradation of a series of commercial polyurethanes on treatment with hydrogen peroxide (25%, 24 h, 100 degrees C) correlated well with their reported susceptibility to environmental stress cracking in vivo. PMID- 8360205 TI - Interaction of heparin with polyallylamine-immobilized surfaces. AB - A new method to bind ionically and remove heparin from solution and dilute serum is described. Utilizing cellulose diacetate (CA) as the polymer substrate, a cationic polymer chain--poly(allylamine)-PALA--was immobilized directly onto the CA surface and onto the surface using poly(ethylene glycol) (PEG) spacer groups. The ionic interaction between the anionic heparin molecule and the cationic PALA polymer is specific and effective to remove heparin from the bulk solution. The binding properties of heparin onto the PALA and PEG-PALA surfaces were examined. The effects of PEG spacers on heparin binding onto the PALA-immobilized surface were investigated by varying the Mw of PEG spacers. PALA (Mw 8500)-immobilized surfaces exhibited enhanced heparin binding. The maximum heparin binding was observed in the region of PEG Mw 2000-4000. For the high-molecular-weight PALA (Mw 50,000)-immobilized surfaces, heparin binding was independent of the molecular weight of PEG. PEG spacers were also evaluated for their ability to prevent or decrease protein (albumin) adsorption. It was observed that at high albumin concentrations, the adsorption of proteins decreased with increasing chain length of PEG, up to Mw 3400. These observations suggest that low-molecular weight PALA (Mw 8500)-immobilized CA surfaces with PEG spacers (Mw 3400) may provide increased heparin binding capacity and decreased protein adsorption. PMID- 8360206 TI - Protein adsorption to poly(ether urethane ureas) modified with acrylate and methacrylate polymer and copolymer additives. AB - To understand better blood interactions with poly(ether urethane urea) (PEUU) materials, a radioimmunoassay and whole or diluted human plasma were used to characterize the presence of fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin on a PEUU formulation and on PEUU formulations modified with the amphiphilic additive Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate] [3/1]), or with hydrophobic acrylate or methacrylate polymer or copolymer additives. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F (Methacrol) or homopoly-DIPAM (h-DIPAM) adsorbed significantly lower amounts of the studied proteins than did either the base PEUU formulations or the PEUUs loaded with the more hydrophobic acrylate or methacrylate polymer additives. Experiments with Methacrol-loaded PEUUs, where the loading of Methacrol was varied from 0.25 wt% to 20.0 wt%, showed that the adsorption of each of the characterized proteins did not vary significantly throughout the Methacrol loading range, and that all Methacrol-loaded PEUU formulations adsorbed significantly lower amounts of the studied proteins than did the unloaded PEUU. Phase separation within the additive loaded PEUUs was characterized by scanning electron microscopy (SEM). The solubility parameters of the additives, as well as of the base PEUU, were calculated and used to interpret differences in phase separation of the additive modified PEUUs. The analysis showed that additives of lower solubility parameter phase-separated into fewer large microdroplets within the PEUU matrix. SEM analysis also showed that additive microdroplets were not present on the air side surface of loaded PEUUs. To explain the differences in protein adsorption to the air side of additive loaded PEUUs when compared to the base PEUU, it was assumed that the additives near this region of the solvent swollen PEUU matrix may have migrated to, at, or near the PEUU-air interface during film formation, creating an additive enriched PEUU surface region. Once at this surface region, it was suggested that dynamic surface reorientation in response to an aqueous medium ensured that the additives were able significantly to influence protein adsorption behavior only if they interacted with aqueous media more favorably than the PEUU. PMID- 8360207 TI - Extracellular matrix analogs as carriers for growth factors: in vitro fibroblast behavior. AB - Repair of connective tissue involves interactions between growth factors (GFs) and extracellular matrix (ECM) molecules. On the other hand, biological biomaterials could be used to carry and deliver GFs to stimulate wound healing. In the present study, fibroblasts were cultivated in a serum-free culture medium onto collagen (type I), hyaluronic acid, chondroitin sulfate, fibronectin, or fibrin. FGF, EGF, or PDGF was incorporated within those substrates. Using immuno- and radiolabeling assays, the distribution of GFs within the ECM analogs was relatively uniform and GFs retained in substrates were dependent on the substrates. Fibroblast replication was determined by the incorporation of [3H] thymidine and compared to control groups. On collagen or chondroitin sulfate, the incorporation of GFs did not significantly improve cell proliferation. On hyaluronic acid, the incorporation of FGF and PDGF enhanced cell replication at 48 h. The incorporation of PDGF in fibronectin enhanced cell replication. On fibrin, the incorporation of PDGF, EGF, and FGF significantly enhanced cell replication. However, cell replication on FGF-incorporated fibrin was higher by 48 h than that on fibrin in the presence of FGF-supplemented culture medium. Fibrin sustains the biological activity of GFs, FGF in particular, and can be a carrier for GF that stimulates cell replication. PMID- 8360208 TI - Bending properties and transformation temperatures of heat treated Ni-Ti alloy wire for orthodontic appliances. AB - The effect of heat treatment temperature on bending properties and transformation temperatures of a Ni-Ti alloy wire, 1.0 mm in diameter, was investigated so that superelasticity could be used in orthodontic appliances needing shape memory processes. The heat treatment process was at 713 K for 1.8 ks and between 673 K and 813 K for 1.8 ks. A three-point bending test and differential scanning calorimetry were performed. The transformation temperatures of the wires were lowered with increasing heat treatment temperature. The reverse transformation finishing temperature was below the body temperature with the treatment above 753 K. Residual deflection of the Ni-Ti wire after bending was small with the secondary heat treatment above 733 K. The load in the unloading process was less changeable and increased with the treatment temperature between 733-813 K. Secondary heat treatment in this range was suitable for using superelasticity in expansion arch appliances. PMID- 8360209 TI - Effect of crosslinking agent content, monomer functionality, and repeat unit chemistry on properties of unfilled resins. AB - Seven mechanical/physical properties were used to evaluate 10 unfilled resins: eight aromatic dimethacrylates and two urethane dimethacrylates. Physical property tests included compressive strength, Young's modulus in compression, uniaxial tensile strength, intrinsic yield point, toothbrush abrasion, Knoop hardness, and water sorption. Controlled changes were made in the following four material parameters: amount of crosslinking diluent present in the uncured monomer, functionality of the monomer, repeat unit chemistry of the monomer (urethane vs. aromatic structure) and mode of activation (chemical vs. visible light). Polymers containing a high concentration of crosslinking agent (50 wt%) were found to be tougher and to possess lower hardness than materials containing lesser amounts of crosslinking agent. This was attributed to the flexible nature of the triethylene glycol dimethacrylate crosslinking molecule. Exposure to water plasticized the highly crosslinked materials to the degree that the yield point and elastic modulus were effectively lowered. Most of the tested properties were unaffected by differences in functionality except resistance to toothbrush abrasion, which was enhanced for polymers derived from high functionality monomers. The urethane-based polymers sorbed substantially more water than the aromatic-based materials, which presumably resulted in lower values for surface hardness. However, the urethane resins were very tough, and excellent resistance to toothbrush abrasion was observed. Property differences caused by differences in activation mode were small, although the visible light materials did sorb more water. PMID- 8360210 TI - Fluoroalkylethyl silane coating as a moisture barrier for dental ceramics. AB - The performance of dental ceramics is reduced in wet environments due to stress corrosion limiting restoration lifetime. As analysis suggests that fracture is typically initiated from the internal surface, placement of a thin coating before a restoration is cemented to place may prevent fracture if it acts as a moisture barrier. Of coatings we tested, a fluoroalkylethyl silane (du Pont MPD-7680) showed promise. This study aimed to test a range of concentrations on glass and to determine any strength improvement on dental ceramics. Glass slides (n = 8-9) were indented (29-N load) stored 24 h, etched, coated with 100, 50, and 25% fluorosilane in isopropyl alcohol, and air-cured for 24 h. The slides were fractured on a biaxial fixture in water at 0.5 mm/min and maximum stresses calculated. Uncoated controls were tested in water and liquid N2 to determine the inert strength without stress-corrosion. Results showed increasing mean strength from uncoated (53.6 MPa) to 100% (68.0 MPa) which compared to the 80.4 MPa inert strength. ANOVA showed P < .05. Subsequently the experiment was repeated on discs of three dental ceramics (n = 7-10): feldspathic (Ceramco), glass-ceramic (Dicor MGC), high-leucite (Optec) with the 100% solution only. Mean strength was significantly (P < .01) enhanced in the feldspathic (56.2 MPa, untreated, 70.7 MPa, treated) but not the high-leucite (83.1, 83.0) or the glass-ceramic (283.9, 271.4). Fluoroalkylethyl silane coating reduced stress-corrosion in glass and feldspathic porcelain. It may be a practical approach to reducing fracture of ceramic restorations. PMID- 8360211 TI - New ideas in biomaterials science--a path to engineered biomaterials. AB - Our existing biomaterials, although demonstrating generally satisfactory clinical performance, were developed based upon a trial-and-error optimization approach rather than being engineered to produce the desired interfacial reaction. Most biomaterials exhibit a nonspecific biological reaction, with sluggish kinetics and a broad spectrum of active processes simultaneously occurring. This article describes materials science nanotechnology, and molecular biology techniques that may permit the synthesis of precisely engineered surfaces. Such surfaces might demonstrate rapid, precise reactions with proteins and cells. This opens the question, "what type of specific surface bioreactions do we want?" New thoughts on biocompatibility are presented that may be helpful in the design of specific surfaces yielding precise, defined biological responses. PMID- 8360212 TI - Behavior of primary bone cells on characterized polystyrene surfaces. AB - Primary bone cells, isolated from the periosteally stripped calvariae of neonate rats, were cultured on 60Co gamma-irradiation-sterilized bacteriologic-grade polystyrene that had been either surface treated with concentrated sulfuric acid or received further gamma-irradiation treatments facilitated cell colonization of the polystyrene compared to those surfaces not treated in the laboratory. x-Ray photoelectron spectroscopy (XPS) showed that the two treatments introduced different chemical groups onto the polymer surface and that cell adhesion was related to gamma-irradiation in a dose-dependent manner. These results show that simple biologic assays, such as cell colonization, are not able to distinguish between differences in surface chemistry demonstrated by such a routinely employed surface analysis technique. Thus, there is a need to develop more sensitive biologic assays that provide functional information of a precision that can be correlated with subtle changes in substratum surface chemistry. Further, we argue that because cells isolated by tissue digestion using proteolytic enzymes respond more readily to changes in the surface chemistry of the substratum they colonize, compared to explanted cells; biologic assays designed for biomaterials testing must take into account changes effected in cell adhesion behavior by isolation procedures. PMID- 8360213 TI - In vivo evaluation of protein adsorption to sterically stabilised colloidal carriers. AB - A diffusion chamber implanted intraperitoneally in the rabbit was employed as an in vivo model to evaluate the interaction of peritoneal proteins with block copolymer (poloxamer and poloxamine)-coated polystyrene microspheres (PS). Using a desorption technique followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, six proteins of 94, 86, 66, 53, 40, and 20 kDa were desorbed from the carrier systems after incubation with peritoneal fluid in vitro. The 40- and 20-kDa proteins dominated the protein profile. A similar pattern was observed when proteins were desorbed from PS microspheres removed after 24-h implantation in chambers in the peritoneal cavity, although the protein profile was dominated by the 94- and 53-kDa proteins. In general, coating of PS with block copolymers reduced the amount of protein bound to the microspheres in vitro and in vivo but did not change the types of proteins bound. PMID- 8360214 TI - Porous collagen sponge for esophageal replacement. AB - A new artificial esophagus with a bilayered structure made of porous collagen sponge and silicone was studied. The concept of this study was not to replace an esophageal defect permanently with prosthesis but to promote tissue regeneration by collagen. Five centimeters of cervical esophagus were replaced by this artificial esophagus in 19 adult mongrel dogs. Two weeks after implantation, the collagen sponge was replaced by autologous tissue and regeneration of the "neoesophagus" was observed in all animals. The inner surface of the neoesophagus was covered with mature mucosal epithelium similar to the intact esophagus 4-5 weeks after implantation. The replacement site was not complicated by infection, anastomotic leakage, or exuberant granulation tissue development on the luminal surface. In a long-term survival study, animals showed moderate-grade stenosis but could take normal feed orally and with no clinical problems observed. PMID- 8360215 TI - Biocompatibility testing of restorative materials influencing dentin and pulp. AB - A comparative study was carried out using 27 healthy human bicuspids that had been extracted for orthodontic reasons from adolescents 11-14 years old. A microphotometrical analysis of buccal and lingual odontoblast layer thickness was performed using the SAMBA 2000 system and the results were submitted to statistical comparison. The buccal odontoblast layer (BOL) was found to be thicker than the lingual odontoblast layer (LOL). These results were independent of age, sex, and tooth position in the dental arch. Moreover, a strong relationship existed between the layer thicknesses as linear function on a logarithmic scale. Standards for the evaluation of pulp-dentin biocompatibility are based essentially upon qualitative or semiquantitative histological criteria. A method of quantitative evaluation based upon microphotometrical measurements of the thickness of the buccal odontoblast layer, considered variable, and the lingual odontoblast layer, considered stable, was applied to coronal filling materials that had previously been tested by a classic method. Seventy bicuspids extracted from adolescents 11-14 years of age whose class-V cavities had been filled in situ with one of four restorative materials, and whole residual dentin thickness was less than 750 microns, were divided into two groups: an intermediate-term group (A) and a long-term group (B); both groups were subdivided into four experimental series as a function of test materials. A microphotometrical analysis was carried out using an automatic scanning system (SAMBA 2000) for the quantification of buccal and lingual odontoblast layer thicknesses. The results confirmed that due to the stability of the LOL thickness it may legitimately be used as reference in the study of the analogous BOL thickness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360216 TI - Gentamicin sulfate attachment and release from anodized Ti-6A1-4V orthopedic materials. AB - A novel method has been developed to attach, retain, and release antibiotics from titanium based materials. This technique consists of forming porous surface coatings by anodizing and using the surface chemical properties of the oxide coatings to attach antibiotics. Coatings with pores in the size range 0.1-0.5 micron have been formed in acid solutions. The attachment and retainment of gentamicin sulfate, a cationic antibiotic, to the coatings has been investigated using microbiological methods. In vitro test results have shown that the duration of antimicrobial activity on the surface of anodized materials is dependent on the porosity and isoelectric point of the coatings. Using microporous oxide coatings formed in phosphoric acid solutions, it has been found that antimicrobial activity could be retained for more than 2 weeks. PMID- 8360217 TI - Cell growth on immobilized cell growth factor. 6. Enhancement of fibroblast cell growth by immobilized insulin and/or fibronectin. AB - A cell growth factor protein (insulin) and/or a cell-adhesion protein (fibronectin) were immobilized on surface-hydrolyzed poly(methyl methacrylate) membranes. The growth of mouse fibroblast cells STO was accelerated by the immobilized insulin. This acceleration was enhanced by introduction of spacer arms. Coimmobilization of insulin and fibronectin was very effective for the acceleration of cell growth. PMID- 8360218 TI - Cell growth on immobilized cell growth factor. 9. Covalent immobilization of insulin, transferrin, and collagen to enhance growth of bovine endothelial cells. AB - Bovine endothelial cells were cultivated on the surface of polyurethane membranes or tubes immobilized with insulin, transferrin, and/or collagen, and growth was measured. For the purpose of immobilization, amino groups were introduced on the membranes or tubes by glow-discharge treatment in the presence of ammonia gas. The proteins were coupled to the amino groups on the surfaces by using dimethyl suberimidate (DMS) or water-soluble carbodiimide (WSC). Growth of bovine endothelial cells was higher on immobilized insulin or transferrin using DMS than that using WSC. The cell growth was higher on immobilized insulin or transferrin than on free insulin or transferrin, respectively. Though immobilized collagen did not affect the cell growth, coimmobilization with insulin or transferrin brought about greater acceleration of cell growth. In addition, the immobilized collagen was indispensible to maintain the endothelial cells on the material surface for a long time. The endothelial cells grown in the polyurethane tubes, on which insulin and collagen are coimmobilized, kept a normal cobblestone-like appearance and maintained the ability to secrete prostacyclin for 9 months. PMID- 8360219 TI - Selective neuronal cell attachment to a covalently patterned monoamine on fluorinated ethylene propylene films. AB - The patterned covalent surface addition of a monoamine to fluorinated ethylene propylene films (FEP) controls both cellular attachment and differentiation in defined media conditions. A radio frequency glow discharge (RFGD) process was used to replace FEP surface fluorine atoms with hydroxyl groups. The primary amine was then covalently attached by polymerizing aminopropyl-triethoxysilane (APTES) via the hydroxyl functionalities. The selective attachment of cells to the APTES regions was determined to be dependent upon the initial adsorption of albumin to the patterned FEP membrane. Albumin was determined to enhance cellular attachment to the APTES regions and prevent attachment to the unmodified FEP areas for both an NB2a neuroblastoma cell line and primary rat endothelial cells. If albumin were not preadsorbed onto the membrane, selective attachment to the modified regions would not occur. Radiolabeling albumin with 125I demonstrated the preference of albumin for adsorption onto the monoamine surface where the cells preferentially attached. Both hydrophobic and ionic forces contributed to the adsorption process. Although selective cellular attachment to the patterned APTES regions could be achieved by albumin preadsorption to the surface, the neuroblastoma cells did not significantly differentiate unless additional serum components were supplemented to the media. PMID- 8360220 TI - Dissolution, leaching, and Al2O3 enrichment at the surface of bioactive glasses studied by solution analysis. AB - Five glass compositions in or near the bioactive region in the system SiO2-Na2O CaO-P2O5-Al2O3-B2O3 were studied in vitro by immersion in Tris buffer. The Si concentration can be taken as a measure of the amount of dissolved glass, whereas the Na concentration can be used to estimate the thickness of the Si-rich (Si gel) layer. Upon immersing a bioactive glass into Tris buffer, a surface layer of a few micrometer thickness is dissolved during the first 8 h. During the first few hours of immersion, the rate of dissolution of the glass network is equal to or exceeds that of the growth of the Si-rich layer. If the glass contains Al2O3, most of the aluminum that would be released due to dissolution of the silica network is enriched in the Si-rich surface layer that forms due to leaching. Al2O3 is not only bonded by the Si gel but also interferes with formation of calcium phosphate. PMID- 8360221 TI - Neocartilage after artificial cartilage repair in the rabbit: histology and proteoglycan fragments in joint fluid. AB - Repair of full-thickness cartilage defects of the rabbit medial femoral condyle with artificial plugs and periosteal grafts was followed for 1 year. The morphological characteristics of the neocartilage after repair and the concentration of proteoglycan fragments in the joint fluid (CPFF) were evaluated. The CPFF showed only a weak correlation to the histological score of the neocartilage. Normal cartilage and subchondral bone did not develop with any of the repair alternatives. With a Dacron plug, neocartilage formation appeared earlier than with natural repair and was better than with periosteal grafting. Increased CPFFs were found in all specimens with repair at 3 months, probably reflecting the remaining effect of surgery. At 6 months, the CPFFs had normalized to control values. At 1 year, the CPFFs were again similar to those at the 3 month evaluation. This was paralleled by a degeneration of the neocartilage. We conclude that Dacron plugs could serve as a scaffold for neocartilage formation. The CPFF reflected surgical trauma and late degeneration of neocartilage but did not indicate minor differences in quality between cartilage repair techniques, probably because of the limited size of the grafted defect. PMID- 8360222 TI - Kinetics of cell proliferation as a function of vascular graft material. AB - Bioresorbable vascular grafts constructed for polyglactin 910 (PG910) and polydioxanone (PDS) and nonresorbable Dacron were interposed into the infrarenal abdominal aortas of New Zealand White rabbits. The prosthesis/tissue complexes were harvested after 2, 3, 4, 12, and 52 weeks. Seventeen, 9, and 1 h prior to sacrifice, animals received tritiated thymidine (0.5 mCi/kg/dose). All specimens were studied grossly and by light and transmission electron microscopy. Mitotic indices (MI's) were determined by autoradiography for inner capsule myofibroblasts at the proximal, mid, and distal segments of each prosthesis. There were no aortic-related deaths. All grafts were patent with no aneurysmal dilatation. At 4 weeks, PG910 resorption was evidenced by macrophage phagocytosis, less so in PDS while Dacron remained intact. At 12 weeks, the PG910 was completely resorbed while PDS resorption continued. The latter was completely resorbed by 52 weeks. There was no significant difference in MI's between proximal, mid, and distal regions for each graft type. The mitotic index paralleled the rate of prosthetic resorption in both PG910 and PDS groups, as high as 28.34 +/- 23.21 in the former 3 weeks after implantation and significantly higher at 4 weeks (7.58 +/- 2.02 and 7.50 +/- 2.66, respectively) than at 52 weeks (0.72 +/- 0.98 and 1.00 +/- 0.22, respectively) in both groups. The mitotic index in the Dacron group never surpassed 1.22 +/- 0.90. We conclude that higher levels of early cell proliferation in bioresorbable grafts closely parallel the kinetics of prosthetic resorption. PMID- 8360223 TI - Use of polyphosphazenes for skeletal tissue regeneration. AB - The hydrolytically unstable polyphosphazenes, poly [(imidazolyl) (methylphenoxy) phosphazenes] and poly [ethyl glycinato) (methylphenoxy) phosphazenes], were studied as potential polymeric supports for cells in tissue regeneration. For bone repair, their specific function would be to support osteoblast growth, forming a bone-polymer matrix. MC3T3-E1 cells (an osteogenic cell line) were seeded onto polymer matrices and cell adhesion and growth as well as polymer degradation were examined. Both imidazolyl- and ethyl glycinato-substituted polyphosphazenes supported the growth of MC3T3-E1 cells. An increase in the content of the imidazolyl side group resulted in a reduction in cell attachment and growth on the polymer surface and an increase in the rate of degradation of the polymer. In contrast, substitution with the ethyl glycinato group favored increased cell adhesion and growth and also an increase in the rate of degradation of the polymers. Thus, the polyphosphazenes represent a system whereby cell growth and degradation can be modulated by varying the nature of the hydrolytically unstable side chain. This in vitro evaluation suggests that the polyphosphazenes may be suitable candidate biomaterials for the construction of a cell-polymer matrix for tissue regeneration. PMID- 8360224 TI - Factors influencing infant mortality in Vietnam. AB - Selected determinants of overall infant mortality in Vietnam were examined using data from the 1988 Vietnam Demographic and Health Survey, and factors underlying neonatal and post-neonatal mortality were also compared. Effects of community development characteristics, including health care, were studied by logistic regression analysis in a subsample of rural children from the 1990 Vietnam Accessibility of Contraceptives Survey. Infant neonatal and post-neonatal mortality rates showed comparable distributions by birth order, maternal age, pregnancy intervals, mother's education and urban-rural residence. Rates were highest among first order births, births after an interval of less than 12 months, births to illiterate mothers and to those aged under 21 or over 35 years of age. Logistic regression analysis showed that the most significant predictor of infant mortality was residence in a province where overall infant mortality was over 40 per 1000 live births. In the rural subsample, availability of public transport was the most persistent community development predictor of infant mortality. Reasons for the low infant mortality rates in Vietnam compared to countries with similar levels of economic development are discussed. PMID- 8360225 TI - Selected determinants of fertility in Vietnam: age at marriage, marriage to first birth interval and age at first birth. AB - Data from the 4172 women aged 15-49 interviewed in the 1988 Vietnamese Demographic and Health Survey were used to examine age at marriage, marriage to first birth intervals and age at first birth. Differences between urban and rural areas, northern and southern provinces and by education of the women were analysed. The majority of the women had their first birth before age 20, but women with secondary education had a significantly higher age at first birth than those with little or no education, and women from the north had a significantly higher age at first birth than women from the south. Rural women and those with little or no education married at significantly younger ages than urban women and those with secondary education; these education effects were confirmed in a rural subsample of women. Women from rural areas and from the north had significantly shorter marriage to first birth intervals than urban women and those from the south, but there were no significant effects related to education. PMID- 8360226 TI - Socioeconomic and environmental determinants of child survival in Bangladesh. AB - Differentials in child survival in Bangladesh have been examined using a number of socioeconomic and environmental factors on data from the 1989 Bangladesh Fertility Survey. Multivariate analysis reveals that both wife's and husband's education and household electricity show a significant positive association with child survival. The respondent's working status exerts a significant negative influence. Wife's education has a greater influence on child survival in Bangladesh than that of husband's education. PMID- 8360227 TI - Influence of son preference on the contraceptive use and fertility of Sri Lankan women. AB - The effect of moderate son preference on family size is analysed using data from the 1982 Sri Lanka Contraceptive Prevalence Survey whose respondents were followed-up in the 1985 Sri Lanka Contraceptive Survey. Reported reproductive intentions on desire for additional children were not always reflected in overall contraceptive use. Complicating factors were the use of modern and traditional methods and the role of induced abortion. Longitudinal observations of the 1982 85 period relating women's individual reproductive behaviour to their intentions show no consistent behavioural difference between those with and without sons. However, at any given parity, the proportion reporting at least one additional child born during the intersurvey period was higher among those women who intended to have at least one additional child than among those who wanted to stop childbearing. This analysis suggests that son preference finds expression more through reproductive intentions than through actual fertility behaviour in the follow-up period. PMID- 8360228 TI - Availability of marriage partners in England and Wales: a comparison of three measures. AB - Measures of partner availability introduced by Goldman, Westoff & Hammerslough (1984) and by Veevers (1988) are described and a new measure of partner availability, the Iterated Availability Ratio, is introduced. The three measures are applied to 1981 Census data for England and Wales and their abilities to predict regional variations in age-specific marriage rates are compared. PMID- 8360229 TI - Effects of biosocial variables on changes in nutritional status of rural Bangladeshi children, pre- and post-monsoon flooding. AB - This study examined the effects of biosocial variables on changes in nutritional status of rural Bangladeshi children, aged less than 2 years, pre- and post-1987 monsoon flooding. Nutritional status was measured by weight for age: variables included were age, sex, sickness during 2 weeks preceding the survey, intake of vitamin A capsules, socioeconomic status of household, and mother's education. A multivariate logistic regression analysis revealed an adverse effect of flood on nutrition and the effect was dependent on sex of child and intake of vitamin A. After the flood the proportion of severely malnourished children was significantly greater among those who had not taken vitamin A. For boys the proportion with severe malnutrition increased after the flood and the increase was greater than for girls; however, boys always had a lower risk of severe malnutrition than girls. PMID- 8360230 TI - Survival in the perinatal period: a prospective analysis. AB - A prospective study of 3080 Filipino mothers and non-twin births in 33 communities is used to study the determinants of mortality in week 1 postpartum. The results show significant nonlinear birth weight effects and the importance of environmental contamination, particularly for infants born by traditional methods at home, and several other intermediate and underlying determinants of perinatal mortality. The pathways through which important sociodemographic factors affect perinatal mortality are also presented. PMID- 8360231 TI - Paediatric care and immunisation among Jordanian children. AB - This paper investigates the behavioural aspects of health care use for Jordanian children from birth to 3 years using data from a national survey. Statistical analyses indicate differences in the determinants of the use of paediatric care and immunisation: whereas immunisation coverage was already good in 1983 (and has improved subsequently), paediatric care is used for fewer than half of the children under 1 year of age. Socioeconomic and demographic characteristics of the population, especially female education, and maternal health care use, are important determinants of these patterns of child health care. The absence of differences in paediatric care and immunisation by sex of the child are discussed. PMID- 8360232 TI - Regional mortality differences in Britain, 1931-87: a two dimensional analysis. AB - In a recent analysis, Illsley, Le Grand & Mullings argued that, over the years 1931-87, regional inequalities in mortality in Britain effectively disappeared for most age groups. The present study reanalyses their data, breaking regional life tables down into their two major components, the level of survivorship, and the shape of the mortality curve. It is shown that whereas there has been a consistent decline in regional inequalities in the level of mortality, there has not been a comparable convergence in the shape of the mortality curves. These shape differences, implying premature adult mortality, are now the major source of variation among the regions. PMID- 8360233 TI - Reaction times and intelligence: a comparison of Chinese-American and Anglo American children. AB - Chinese-American and Anglo-American school children were compared on a nonverbal test of intelligence (Raven's Progressive Matrices) and on twelve chronometric variables which measure the speed with which basic information processes (e.g. stimulus apprehension, decision, and discrimination) can be carried out. All of these tasks are correlated with psychometric intelligence. The two groups differed significantly on most of the variables, but the differences appear to be multidimensional and are not simply due to a group difference in psychometric intelligence, equivalent to about 5 IQ points in favour of the Chinese-Americans. The results are compared with those of Lynn and his colleagues on Bristish, Japanese, and Hong Kong children, and both consistencies and inconsistencies are found. PMID- 8360234 TI - Teenage sexual activity in Zambia: the need for a sex education policy. AB - Data from a study of teenage sexual activity among secondary school girls show the need for a sex education policy as a first step in controlling teenage fertility in Zambia. A large proportion of teenage females enter into close relationships with males at young ages and a high proportion of young females have engaged in sexual intercourse. Most of these sexually active females do not use family planning methods even though a large proportion of them have heard of modern methods. The teenagers receive very little sex education from their parents and a modern institutional sex education programme is needed. PMID- 8360235 TI - Infant and child mortality in rural Egypt. A comment. PMID- 8360236 TI - A simple, effective system for assessing viability in split-thickness skin with the use of oxygen consumption. AB - To address the recognized need for better viability-assessment techniques in the banking of allograft skin, we have developed a simple, effective, and easily constructed system for measuring the aerobic activity in small skin samples. The system consists of a microcomputer interfaced to a Clark-type polarographic oxygen electrode to measure oxygen concentrations in discs (5 mm diameter) of split-thickness skin. The system allows simultaneous data acquisition and an on screen display of oxygen readings on a linear or logarithmic scale. The computer program quantifies the rate of oxygen consumption by calculating a linear regression of oxygen measurements between 100 and 600 seconds. Data are stored in a standard format for easy transfer to commercial software packages for further analysis. The kinetics of oxygen consumption by porcine split-thickness skin stored at 4 degrees C for up to 21 days was assessed with this technique and showed a gradual decline in rate as function of storage time, reaching 50% recovery after 6 days. This assay is a simple and inexpensive method to establish and perform, thus making it suitable as a routine assay for use in the banking of skin and other tissues. PMID- 8360237 TI - A review of the biophysical basis for the clinical application of electric fields in soft-tissue repair. AB - Interest in the role of electrical interactions as epigenetic regulators of wound healing had its beginnings nearly 40 years ago. Because the mechanisms of action are not understood (which obviates rational therapy), the empiric application of fields to wounds has produced mixed results. However, taken collectively, clinical trials have demonstrated some beneficial effects. Tests on soft tissues of animals have shown that electric stimulation can influence the rate of wound healing and scar strength. Natural epithelial-derived sodium currents have been discovered in the wounds of invertebrates and mammals. It is theorized that these currents may be a normal controlling factor in wound healing. Therefore, perturbation of these signals is important to understand. The purpose of this review is to put into proper perspective the biophysical, physiological, and clinical data pertaining to use of electricity to control wound healing, with the goal of minimizing much of the prevailing confusion. PMID- 8360238 TI - Relationship between extent of burn injury and magnitude of microbial translocation from the intestine. AB - The gut can be a source of sepsis after thermal injury. In the present study the relationship between the extent of burn injury and magnitude of bacterial translocation was investigated. Mice underwent 0%, 10%, 20%, 30%, or 50% total body surface area full-thickness burn and simultaneous gavage with 1 x 10(10) 14C labeled Escherichia coli. mesenteric lymph nodes, liver, spleen, peritoneal fluid, and burn wound were excised 4 hours after burn injury. Residual radioactivity and bacterial colony counts were measured, and percentages of viable organisms were calculated. Results showed that the rate of translocation of 14C E. coli increased proportionally with the burn size, reaching a maximum at 30%. The cutaneous eschar collected a remarkable amount of labeled bacteria, suggesting enteric microflora as a possible source of contamination of the burn wound via endogenous routes. The percentage of viable organisms in the tissues demonstrated that the ability of mesenteric lymph nodes, liver, and eschar to clear translocated bacteria was directly affected by the severity of the burn injury. PMID- 8360239 TI - A systematic approach to flap selection for the axillary burn contracture. AB - Any soft-tissue deficiency about the axilla unfortunately may readily be translated into a functional limitation of the upper extremity that should be addressed in a simple yet expeditious fashion. Commonly a sequela of burn injuries, significant skin destruction in kind must be restored. Whatever the etiology of major deformities, the vital axillary structures and preservation of shoulder range of motion may best be accomplished by resurfacing with the use of vascularized tissues taken from sources adjacent to the defect. If this is the case, the efficacious application of these local muscle or fascial flaps mandates a realization that such choices are finite in number. A schema for a reasonable flap selection process has been devised based on the relative severity and anatomic location of the axillary burn scar contracture. PMID- 8360240 TI - Evaluation of the Unna Boot for lower-extremity autograft burn wounds excoriated by pruritus in pediatric patients. AB - Six pediatric patients with lower-extremity excoriated autografts secondary to pruritus were treated randomly. Group 1 was treated with application of an Unna Boot that was changed every 7 days; Group 2 was treated with conventional dressing and antihistamines. Average time for complete wound closure was similar in the two groups: 32 days for group 1 versus 36 days for group 2. Treatment of group 1 cost $19.80/wk compared with $30.90/wk for treatment of group 2. The time for dressing change was 15 min/wk for group 1 and 3.5 hr/wk for group 2. The parents in group 1 gave their children better scores when asked about appetite, sleep, and play patterns. PMID- 8360241 TI - Anal stenosis with megarectum: an unusual complication of a perineal burn. AB - A case of a 3-year-old boy with anal stricture and megarectum is described. Overflow incontinence and soiling were corrected by local flaps and skin graft and were maintained by frequent dilatations after downward traction of the whole anus was performed. The options of immediate and late treatment of such burns and the colostomy procedure are discussed. PMID- 8360242 TI - Release of the first web space with the "goalpost" procedure in pediatric burns. AB - First web-space contractures commonly occur in dorsal and palmar hand burns. Both abduction and extension limitations develop as a result of reduction in thumb motion. Optimal treatment of first web-space contractures should treat both abduction and extension deformities and should minimize the need for reoperation in growing children. Many techniques exist to manage web-space contractures. This article describes a long rectangular flap release ("goalpost" procedure) used to treat first web deformities in pediatric patients with burns. During the period 1987 through 1989, 31 first web-space releases were performed in 23 patients (mean age 9.2 years). The operations were performed a mean of 50 months after burn injury. No wound complications occurred and no patient required repeat operation in the follow-up period. Range of motion in abduction and extension was increased a mean of 10 degrees. The goalpost procedure is a highly acceptable alternative to standard web-space releases and offers advantages in its ability to treat both abduction and extension contractures. PMID- 8360243 TI - Fibrin glue: its use for skin grafting of contaminated burn wounds in areas difficult to immobilize. AB - A human fibrin glue was used in patients with burns for fixation of skin grafts on slightly infected wounds in the axillas, perineum, and the gluteal folds. These areas had been left open after previous skin transplantations. There was stable and safe adhesion and little inflammatory reaction between the graft and the recipient area, resulting in favorable conditions for graft incorporation. By using the glue the last wounds in our patients healed earlier, and the patients' general condition improved. PMID- 8360244 TI - Omiderm as an initial burn dressing. PMID- 8360245 TI - Reasons for the selection of burn-scar-support suppliers by burn centers in the United States: a survey. AB - Several companies currently market anti-burn-scar pressure garments to burn centers. Because of the numerous available choices, decisions about the reasons for selecting a garment are often confusing to those who are responsible for ordering the supports. This study was conducted to assist in decision making about garment selection by determining the relative importance of various factors in selecting brands of anti-burn-scar supports. A survey questionnaire was sent to 101 randomly selected burn centers in the United States, asking about the reasons for their choice of pressure-support suppliers. Sixty-two survey (61%) respondents indicated factors used in selection of a manufacturer. The factors included ease of accessibility for orders (97%), ease of measurement methods (90%), reliability of fit with the first garment ordered (90%), ability to fashion either a nonstandard support (77%) or special options into a garment (76%), provision of measurement materials (65%), and costs of the support (63%). Availability of standard garment options (50%) and/or choice of colors (31%) were listed less frequently. Twenty-four burn centers (39%) use only one company for orders, whereas 20 (31%) use two, 9 (15%) use three, and 9 (15%) use four different suppliers. Industry responses to these findings were gathered and presented as well. The results of this survey would indicate that burn staff have viable options of pressure-garment suppliers to assist them in responding to the scar-control needs of their patients. PMID- 8360246 TI - Development of a computerized registry for the patient with burns: Part II. PMID- 8360247 TI - Hardiness, stress, and burnout among intensive care nurses. AB - The purposes of this study were to determine whether hardiness is a predictor of burnout and whether it can buffer the effect of stress on burnout. Thirty-one registered nurses who work in intensive care units completed the Hardiness test, the Nursing Stress scale, and the Tedium scale. Descriptive statistics, correlational statistics, t tests, analysis of variance, and hierarchical multiple regressions were used to analyze the data. Results indicated that hardiness and burnout had a significant inverse relationship (r = 0.66). Stress and the stress-hardiness interaction term accounted for 29% of the variance in burnout scores. This study found hardiness to be a predictor of burnout and a buffer in the stress-burnout relationship. Furthermore, the relationship between hardiness and stress was found to be stronger than that between stress and burnout. Further study is needed to verify that hardiness is a stress mediator in nursing and to determine how to best promote hardiness in nurses. PMID- 8360248 TI - Burns caused by flambe foods. AB - From 1978 to 1990, five patients were admitted to the hospital for treatment of burns that were sustained during the preparation of flambe foods in restaurants. Three patients were patrons, and two were waiters. The average body surface area involved was 14% (range 10% to 18%). The average area of full-thickness burn was 3% (0% to 10%). All patrons required long-term psychologic support and were involved with lengthy and expensive litigation proceedings. The two waiters lost a total of 5 months from work. Although these injuries are quite rare, it is hoped that they can be totally prevented by adherence to certain safety guidelines. PMID- 8360249 TI - Tasks of bereavement for burn center staffs. AB - Considerable research and theoretic work is reviewed to identify the major tasks of the grieving process. These tasks are diffusing the emotional energy of loss, reknitting the social fabric, and forming a new relationship with the deceased. A narrative approach to understanding human experiences is outlined, and specific application is given to the grieving process. Through the use of a narrative report of the death of twins in a hospital burn unit, the tasks of grieving are applied to professionals who work with patients with burns. Finally, practical suggestions for help with the tasks of grieving in a burn center are offered. PMID- 8360250 TI - Therapeutic abortion in a severely burned woman. PMID- 8360251 TI - The die is cast: telling patients they are going to die. PMID- 8360252 TI - Human branding in college fraternities: round-up time at "animal house". PMID- 8360253 TI - Packaging zinc, fibrinogen, and factor XIII in platelet alpha-granules. AB - Zinc(II) accumulated by platelets has profound effects on platelet activity. This study is focused on the distribution of Zn(II) between human platelet subcellular compartments. After incubation with 86Rb+ and platelet lysis, the organelles were separated by sucrose density gradient centrifugation. Fibrinogen served as a marker for alpha-granules. 86Rb+ and factor XIII served as markers for the cytoplasmic fractions. Zn(II) was found to be distributed between the cytoplasm and the alpha-granules, with variations between different individual units. The total platelet Zn concentration and its relative subcellular distribution were dependent on its extracellular level. Incubation of platelets with 100 microM Zn(II) resulted in a twofold increase of its level in the cytoplasm and by one order of magnitude in the alpha-granules. In addition to the anticipated factor XIII activity in the cytoplasmic pool fraction, we found thrombin-inducible factor XIII activity within the alpha-granules. Immunoblotting confirmed the presence of both the a and b subunits of plasma factor XIII (a2b2 form) in the alpha-granules. As fibrinogen is not synthesized in the platelet, we propose that by virtue of their mutual binding, fibrinogen, Zn(II) and plasma factor XIII-a2b2 are simultaneously taken up into the alpha-granules by endocytosis, presumably through the vehicle of the GPIIb/IIIa fibrinogen receptor. A rationale for co packaging these components within the alpha-granules is that Zn(II) inhibits factor XIII activity and thereby prevents the premature cross-linking of the concentrated fibrinogen prior to platelet activation and secretion. By contrast, cytoplasmic Zn(II) may increase platelet responsiveness to agonists due to its interaction with cytoplasmic modulators of platelet activity. PMID- 8360254 TI - Comparative analysis of mitogenic and morphogenic effects of HGF and EGF on rat and human hepatocytes maintained in collagen gels. AB - Hepatocytes maintained in collagen gels remain differentiated for prolonged periods of time compared to cells maintained on conventional cultures. Previous studies with other culture systems in which chemical supplements or substratum modifications enhanced hepatocyte differentiation showed that in all of these systems hepatocytes do not respond to mitogens. In this study it is shown that hepatocytes maintained between two layers of collagen gels respond to mitogens HGF (also known as scatter factor (HGF/SF)) and epidermal growth factor (EGF). Cell density did not affect the responsiveness to mitogens as in conventional cultures. In addition both mitogens (HGF more pronounced) induce characteristic morphogenic changes in which hepatocytes form processes and join in formation of cords. Hepatocytes respond to mitogens for up to 6 days in culture at which point they become refractory to further mitogenic stimulation. This occurs despite electron microscopic evidence that these cells are fully viable when they become refractory to mitogenesis. The refractory state is not modified by substitution of one growth factor for the other or by addition of growth factors at different times. Hepatocytes in the refractory state become again responsive to mitogens when the collagen gels are dispersed by collagenase and the cells are replated on conventional substrates. PMID- 8360255 TI - Effect of floating a gel matrix on mucin release in cultured airway epithelial cells. AB - Confluent cultures of primary hamster tracheal surface epithelial (HTSE) cells grown on a thick collagen gel are highly enriched with secretory cells and constitutively release mucins. In the present experiment, we examined the possible effect of mechanical strain of cultured HTSE cells on the release of mucin. The mechanical strain of cells was accomplished by several methods: 1) by floating the gel from the culture dish by rimming; 2) by treatment with EGTA which interrupts intercellular tight junctions; 3) by treatment with collagenase which disrupts the cell-matrix adhesion; and 4) by mechanically flexing the collagen gel matrix. All these conditions caused increases of mucin release without damage on the plasma membrane. We conclude that a number of mechanical strains which might alter cell shape can stimulate mucin release from cultured HTSE cells. Such a mechanism might be operative in the physiological regulation of airway goblet cell mucin secretion where mechanical strains may be induced on epithelial cells by underlying smooth muscles. PMID- 8360256 TI - Activation of protein kinase C inhibits human keratinocyte migration. AB - The involvement of protein kinase C (PKC) in epidermal growth factor (EGF) induced human keratinocyte migration was studied with the phagokinetic assay. It was concluded that PKC activation does not mediate, but rather inhibits, EGF induced keratinocyte migration. The following experimental observations support these conclusions: 1) The PKC inhibitor H-7 did not inhibit EGF-induced migration but instead led to a modest enhancement. 2) PKC activators such as phorbol-12 myristate-13-acetate (PMA), phorbol-12,13-dibutyrate (PDBu), and 1,2-dioctanoly sn-glycerol inhibited migration, but biologically inactive 4 alpha-PMA had no effect. 3) PMA did not inhibit keratinocyte attachment and spreading but blocked migration almost immediately after addition. 4) Migration of PKC-depleted cells, which were produced by prolonged treatment with PDBu, was enhanced similarly to normal cells by EGF. 5) PKC-depleted cells were not susceptible to the inhibitory effects of phorbol esters on migration. Additional experiments, in which cells were preactivated with EGF, suggested that PKC inhibits the EGF effect at a post receptor level. The inhibitory effect of PKC on keratinocyte migration was not restricted to EGF-induced migration; PKC activation also inhibited keratinocyte migration induced by bovine pituitary extract, insulin, insulin-like growth factor-1, and keratinocyte growth factor. PMID- 8360257 TI - Expression of transforming growth factor alpha antisense mRNA inhibits the estrogen-induced production of TGF alpha and estrogen-induced proliferation of estrogen-responsive human breast cancer cells. AB - To ascertain if 17 beta-estradiol (E2)-induced proliferation could be attenuated by blocking the expression of endogenous transforming growth factor alpha (TGF alpha), estrogen receptor (ER)-positive, estrogen-responsive MCF-7 or ZR-75-1 cells and ER-negative, estrogen-nonresponsive MDA-MB-468 or HS-578T cells were infected with a recombinant amphotropic, replication-defective retroviral expression vector containing a 435 base pair (bp) Apa1-Eco R1 coding fragment of the human TGF alpha cDNA oriented in the 3' to 5' direction and under the transcriptional control of an internal heavy metal-inducible mouse metallothionein (MT-1) promoter and containing the neomycin (neo) resistance gene. E2-stimulated expression of endogenous TGF alpha mRNA was inhibited by 4-5 fold, and the production of TGF alpha protein was inhibited by 50-80% when M-1 mass-infected MCF-7 or MZ-1 mass-infected ZR-75-1 cells were treated with 0.75-1 microM CdCl2, whereas in comparably treated parental MCF-7 or ZR-75-1 cells there was no significant effect upon these parameters. E2-stimulated anchorage dependent growth (ADG) and anchorage-independent growth (AIG) of the M-1 or MZ-1 cells was inhibited by 60-90% following CdCl2 treatment. In contrast, neither the ADG nor AIG of the parental noninfected MCF-7 or ZR-75-1 cells that were maintained in the absence or presence of E2 was affected by comparable concentrations of CdCl2. The ADG and AIG of TGF alpha antisense MD-1 mass infected MDA-MB-468 cells that express high levels of endogenous TGF alpha mRNA were also inhibited by 1 microM CdCl2, whereas the ADG and AIG of MH-1 mass infected HS-578T cells, a TGF alpha-negative cell line, were unaffected by CdCl2 treatment. These results suggest that TGF alpha may be one important autocrine intermediary in regulating estrogen-induced cell proliferation. PMID- 8360258 TI - Importance of cell aggregation for expression of liver functions and regeneration demonstrated with primary cultured hepatocytes. AB - Adult rat hepatocytes aggregated to form floating multicellular spheroids when cultured in Primaria dishes, which have a positively charged surface, in serum free Williams' medium E (WE) supplemented with insulin and epidermal growth factor (EGF). These hormones were essential for maintenance of the spheroids, whereas the size of the spheroids depended on the inoculum cell density. The spheroids retained in vivo levels of expressions of albumin and glucokinase and synthesized scarcely any DNA even in the presence of insulin and EGF. On transfer to type I collagen-coated dishes, the spheroids gradually disaggregated and the cells formed monolayers, in which the expressions of albumin and glucokinase were suppressed and DNA synthesis and hexokinase activity were increased. DNA synthesis of hepatocytes in monolayer culture was maximal 24 hr after transfer of the spheroids, approximately 80% of the hepatocyte nuclei were labelled with bromodeoxyuridine during culture for 48 hr, and the mitotic index was approximately 70% after 60 hr. These results suggest that, in spheroids, hepatocytes remained in the G0 phase, but that when they formed monolayers, they progressed to the G1 phase and proceeded through the cell cycle in the presence of insulin and EGF. This work shows that the cell cycle of hepatocytes in culture can be manipulated by providing conditions for quiescence as spheroids or growth as monolayers and that the shape of hepatocytes is important for regulating their growth and liver-specific functions. PMID- 8360259 TI - Thrombin receptor activating peptides induce Ca2+ mobilization, barrier dysfunction, prostaglandin synthesis, and platelet-derived growth factor mRNA expression in cultured endothelium. AB - Endothelial cell activation by thrombin is a key event in wound healing, inflammation, and hemostasis. To better define thrombin-endothelial cell interactions we synthesized several peptides of varying length corresponding to the initial 14 amino acid sequence of the cloned human platelet thrombin receptor after cleavage at an arginine41 site (R/SFLLRNPNDKYEPF). Thrombin receptor activating peptides (TRAPs) as short as 5 amino acids induced significant levels of PGI2 synthesis and expression of PDGF mRNA in human endothelium and produced dose-dependent cellular contraction and permeability of confluent human umbilical vein and bovine pulmonary artery endothelial monolayers. To explore whether TRAPs utilized similar signal transducing pathways as alpha-thrombin to accomplish endothelial cell activation, phospholipase C production of the Ca2+ secretagogue IP3 was measured and detected 10 seconds after either TRAP 7 or alpha-thrombin. Furthermore, TRAPs ranging from 5-14 residues induced significant dose-dependent increases in Fura-2 fluorescence indicative of Ca2+(1) mobilization. These results indicate that thrombin-mediated proteolytic cleavage of the human and bovine thrombin receptor initiates stimulus/coupling responses such phospholipase C activation, Ca2+ mobilization, and protein kinase C activation. The functional consequence of this cellular activation via the cleaved receptor is enhanced cellular contraction, barrier dysfunction, PGI2 synthesis, and expression of PDGF mRNA. PMID- 8360260 TI - Contributions of K+, Na+, and Cl- to the membrane potential of intact hamster vascular endothelial cells. AB - The transmembrane potential (Vm) of vascular endothelial cells (EC) is an important property that may be involved in intra- and intercellular signal transduction for various vascular functions. In this study, Vm of intact aortic and vena caval EC from hamsters were measured using conventional microelectrodes. Vascular strips with the luminal surface upwards were suffused in a tissue chamber with Krebs solution in physiological conditions. The resting Vm of aortic and vena caval EC was found to be -40 +/- 1 mV (n = 55) and -43 +/- 1 mV (n = 15), respectively. The Vm recordings were confirmed to have originated from EC by scanning and transmission electron microscopy combined with the comparison of electrical recordings between normal and endothelium-denuded aortic strips. The input resistance varied from 10-240 M omega, which implied the presence of electrical coupling between vascular EC. Elevating the K+ level in the suffusate from 4.7 mM to 50 and 100 mM depolarized aortic EC by 19% and 29% and vena caval EC by 18% and 29%, respectively. These low percentages indicated a relatively small contribution of [K+] to the resting Vm of vascular EC. A positive correlation (r > 0.69) between the resting Vm and the magnitude of depolarization by the high [K+]o may be related to the involvement of voltage-dependent K+ channels. The hyperpolarization caused by lowering both [Na+]o and [Cl-]o suggested the disengagement of some electrogenic transport systems in the membrane, such as a Na(+)-K(+)-Cl- cotransporter. The transference number (t(ion)), as an index of membrane conductance for specific ions, was calculated for K+ (15-20%), Na+ (16%), and Cl- (9-15%), demonstrating that both Na+ and Cl- as well as K+ contribute to the overall resting Vm. Our study documented some basic electrophysiology of the vascular EC when both structural and functional properties of the cell were maintained, thus furthering the understanding of the essential role of endothelial cells in mediating vascular functions. PMID- 8360261 TI - Amiloride-dependent transport is the main mechanism implicated in sodium influx regulation in rat mast cells. AB - Mast cell sodium regulation is a largely unknown field. In our effort to study the mechanisms by which mast cells regulate sodium levels, we have examined the effect of amiloride and ouabain on 22Na entry in rat mast cells in isotonic and hypertonic conditions. Ouabain (0.5 mM) enhances sodium uptake by 32% in isotonic conditions. Hypertonicity increases by 400% the uptake of sodium through an amiloride (1 mM) dependent mechanism. Ouabain has no appreciable effect on the entry of 22Na in hypertonic conditions. PMID- 8360262 TI - Apotransferrin stimulation of thyroid hormone dependent rat pituitary tumor cell growth in serum-free chemically defined medium: role of FE(III) chelation. AB - Triiodothyronine (T3) dependent growth of GH1 rat pituitary tumor cells in serum free defined culture requires apotransferrin (apoTf) (Sirbasku et al.: Mol. Cell. Endocrinol., 77:C47-C55, 1991). Diferric transferrin (2Fe.Tf) also is necessary as an iron source (Eby et al.: Anal. Biochem., 203:317-325, 1992). Further, T3 dependence is prevented by soluble Fe(III) addition to the medium (Sato et al.: In Vitro Cell. Dev. Biol., 27A:599-602, 1991). While our data suggested that apoTf caused growth by chelation of Fe(III), direct evidence was required. We used urea polyacrylamide gel electrophoresis along with autoradiography and Western immunoblotting to measure the Fe(III) content of growing GH1 cell cultures and identify the apoTf, mono-metal transferrins and 2Fe.Tf present. We found that apoTf per se did not cause growth but instead chelated inhibitory levels of Fe(III). In fact, apoTf need not be present at all provided that Fe(III) is reduced to < or = 0.6 microM. In addition, other protein and non protein Fe(III) chelators were shown to be as effective as apoTf. Here, we report that pituitary cells are completely inhibited by > or = 1.2 microM Fe(III), which are concentrations which might be expected in many culture media and usually are not thought to influence growth. The high sensitivity of pituitary cells to Fe(III) suggests further study to determine what cellular functions are affected and how they interfere with thyroid hormone dependence. PMID- 8360263 TI - An N-cadherin-like protein contributes to solute barrier maintenance in cultured endothelium. AB - We investigated the role of cadherins in the solute barrier maintained by endothelial cells in vitro. Cell-column chromatographic measurement of endothelial barrier showed that reducing normal extracellular calcium from 1.2 to 0.12 mM increased endothelial permeability to 250% of baseline after 20 min. Restoring normal calcium restored the barrier within 15 min which remained stable for at least 60 min. We used sulfo-NHS-biotin and anti-cadherin antibodies to characterize endothelial proteins with possible roles in the maintenance of endothelial barrier. The non-specific probe sulfo-NHS-biotin identified at least ten endothelial cell surface proteins, with greatest labelling occurring at molecular weights of 125 and 145 kD. Six proteins, including the 125 and 145 kD proteins, associated with the cytoskeleton. Western blotting for the presence of classical cadherins containing the conserved cytoplasmic sequence CDPTAPPYDSLLVFDYEG detected two bands at 145 and 125 kD which associated with the cytoskeleton. Western blotting with an antibody, which recognizes FHLRAHAVDINGNQV, an extracellular homotypic binding region of N-cadherin, detects three bands. Of these three, one protein had a molecular weight of 125 kD and was associated with the cytoskeleton. Immunofluorescence with both N-cadherin and anti-peptide 1 antibodies found staining at endothelial cell borders. The utility of a newly developed cell-column calcium switch assay was tested by verifying the functional role of the previously described epithelial cadherin, uvomorulin, in epithelial barrier. We then applied this method to endothelial cell columns and found the N-cadherin antibody interfered with the reforming of interendothelial junctions. These results suggest that, as in epithelial cells, cadherins in bovine endothelial cells have a functional role in forming the calcium sensitive endothelial junction and may play an important role in the formation of normal barrier. PMID- 8360264 TI - Heat shock protein is a unique marker of growth arrest during macrophage differentiation of HL-60 cells. AB - Prior to morphologic and functional maturation, terminally differentiating hematopoietic cells first exit the cell cycle and undergo growth arrest. Relatively little is known about which molecules regulate differentiation-induced growth arrest. In the present report, we sought to determine whether the mammalian low molecular weight heat shock protein (hsp28) was a candidate growth regulatory molecule during human hematopoiesis. To this end, hsp28 protein expression was examined during phorbol ester (PMA)-induced macrophage differentiation of the human HL-60 promyelocytic leukemic cell line. Whereas hsp28 was constitutively expressed at relatively low levels in an unphosphorylated state, hsp28 was rapidly phosphorylated within 4 hr following PMA-induced differentiation, preceding increased hsp28 protein levels at 24-48 h. In contrast to other differentiative agents, hsp28 steady state mRNA and protein were regulated concordantly in response to macrophage differentiation. More importantly, these changes were transient, and occurred concomitant with the down regulation of cellular proliferation and the onset of G1 phase cell cycle arrest. In total, these observations implicate hsp28 as an intermediary in the myelomonocytic differentiative pathway of promyelocytic leukemic cells, and will shed light on the events regulating this process. PMID- 8360265 TI - Characterization of system L and system y+ amino acid transport activity in cultured vascular smooth muscle cells. AB - The uptake of L-leucine and L-lysine into vascular smooth muscle cells cultured from the aortas of rats has been investigated. Both amino acids are taken up by saturable systems that are independent of the presence of a Na+ gradient and can be stimulated in trans by neutral bulky amino acids for leucine and cationic amino acids for lysine. Leucine uptake is inhibited competitively in cis by several neutral amino acids, whereas lysine uptake is inhibited strongly by other cationic amino acids but also significantly by neutral amino acids such as leucine. The leucine inhibition is noncompetitive. Cells preloaded with leucine and lysine could also export these amino acids and the rate of efflux was stimulated by the presence of appropriate amino acids in trans. These data are all consistent with leucine being transported largely if not entirely by System L and lysine by the System y+ transporter. PMID- 8360266 TI - A novel member of the dynamin family of GTP-binding proteins is expressed specifically in the testis. AB - Dynamin is a member of a new GTPase family, which includes the mouse Mx protein, the yeast VPS1 and the Drosophila shibire gene product. A high homology with the shibire product suggests a role for dynamin in the endocytotic process, but it is expressed only in mature neurons. We identified two additional dynamin-like proteins in rats, by using the polymerase chain reaction with degenerate primers corresponding to the GTP-binding areas conserved between dynamin and VPS1. The full coding sequence of one of them, dynamin-2, revealed that it has 848 amino acids and has great similarity with brain dynamin and the shibire product. Northern blot analysis and in situ hybridization revealed its expression to be specific to the seminiferous tubules in the testis. Dynamin-2 (testis type dynamin) was expressed in germ-cell-depleted testis as well, indicating its expression in Sertoli cells. Our data imply that a number of dynamin family proteins, which are products of distinct genes, may play different roles specific to each cell type in the same rat. PMID- 8360267 TI - Inhibition of transcription blocks cell cycle progression of NIH3T3 fibroblasts specifically in G1. AB - We have analysed the role of RNA polymerase II-dependent transcription in cell cycle progression. Time-lapse video recording and cytogenetic analysis were used to determine the sensitivity of NIH3T3 cells to the RNA polymerase II inhibitor alpha-amanitin at different stages of the cell cycle. Our results show that alpha amanitin blocks cells specifically in G1, irrespective of the concentration within the range of 3 to 30 micrograms/ml. This indicates that transcription in G1 is required to overcome a restriction point located in this phase of the cell cycle. In agreement with this conclusion is the requirement for an uninhibited protein synthesis during G1 progression. In addition, the insensitivity of S phase cells to RNA polymerase II inhibition suggests that the transcription of genes thought to be normally induced during S/G2 is not required for the completion of an ongoing cell cycle. S/G2 progression was however clearly dependent on protein synthesis. This suggests that cells exposed to alpha amanitin are able to complete their cell cycle because sufficiently high levels of mRNA are present in S/G2 due to basal level transcription, or are left from preceding cell cycles. It is therefore unlikely that transcriptional regulation in S or G2 plays a crucial role in the control of cell cycle progression in NIH3T3 cells. PMID- 8360268 TI - Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent human fibroblasts. AB - The state of cellular senescence is characterised by an irreversible arrest in the G1 phase of the cell cycle. It has previously been shown that three cell cycle genes, cyclin A, cyclin B and cdc2, are not expressed in senescent human fibroblasts. All three gene products have functions after S-phase entry, so that their suppression cannot explain the irreversible G1 arrest. Here, we report that the abundance of transcripts from two other cell cycle genes, cdk2 and cdk4, thought to act during G1-->S progression, is significantly diminished in senescent cells of the diploid human fibroblast line WI-38. Surprisingly, two other cyclins, D1 and E, behave in a completely different way, in that their expression is elevated in senescent cells, especially under conditions of serum starvation. Both the synthesis and the steady-state level of cyclin D1 protein were also found to be markedly higher in senescent cells (3- to 6-fold). Cyclins D1 and E are thus the first genes shown to be overexpressed or deregulated in senescent cells. It is tempting to speculate that this deregulation may be due to the absence, in senescent cells, of a regulatory loop that would normally control their expression. This is supported by our finding that cyclin E-associated kinase activity in senescent cells is reduced approx. 14-fold. Our data also suggest that the deregulated expression of cyclin D1 and E is not sufficient to drive senescent cells into DNA replication. PMID- 8360269 TI - gamma-Tubulin participates in the formation of the midbody during cytokinesis in mammalian cells. AB - Animal cells undergoing cytokinesis form an inter-cellular bridge containing two bundles of microtubules interdigitated at their plus ends, which constitute the midbody. Polyclonal antibodies raised against three specific amino acid sequences of gamma-tubulin (EEFATEGGDRKDV, NIIQGEADPTDVHKSL and EYHAATRPDYISWGTQEQ) specifically stained the centrosome in interphase, the spindle poles in all stages of mitosis, and the extremities of the midbody in mammalian cells (Potorous, human, Chinese hamster, mouse). This staining was prevented by the corresponding peptides, by Xenopus gamma-tubulin, but was not modified by purified alpha beta-tubulin heterodimer. An identical staining was obtained with affinity-purified antibodies against the carboxyl-terminal amino acid sequence of human gamma-tubulin. No gamma-tubulin could be detected in the interzone during anaphase and early telophase. Material containing gamma-tubulin first appeared in the two daughter cells on each side of the division plane in late telophase, and accumulated transiently at the minus ends of the two microtubule bundles constituting the midbody for one hour after metaphase. Micro-injection of gamma tubulin antibodies into anaphase cells prevented the subsequent formation of the microtubule bundles between the two daughter cells. In contrast with previous views, these observations suggest that the microtubules constituting the midbody may be nucleated on special microtubule organizing centres, active during late telophase only, and assembled on each side of the dividing plane between the daughter cells. PMID- 8360270 TI - gamma-Tubulin is present in acentriolar MTOCs during early mouse development. AB - gamma-Tubulin, a recently discovered member of the tubulin superfamily, is a peri centriolar component considered to be essential for microtubule nucleation. Mouse oocytes and early embryos lack centrioles until the blastocyst stage. Thus, early mouse embryos allowed us to study the location of gamma-tubulin in animal cells in the absence of centrioles. For this, we used an antiserum directed against a specific peptide of the gamma-tubulin sequence, which is conserved among species. This serum has been characterised both in PtK2 and mouse cells. We found that it specifically-stained the spindle poles and the cytoplasmic microtubule organizing centers in metaphase II oocytes and the spindle poles in mitosis during the cleavage stages. In contrast, no interphase staining could be detected during cleavage. Since the overall level of gamma-tubulin did not decrease during interphase, as shown by immunoblotting experiments, this absence of staining during interphase is probably due to a cytoplasmic dispersion of gamma-tubulin. A single dot-like interphase reactivity appeared at the 32-cell stage. In parallel, electron microscopy studies allowed us to detect centrioles for the first time at the 64-cell stage. The possible roles of gamma-tubulin in microtubule nucleation and in centrosome maturation are discussed. PMID- 8360271 TI - Stress-relaxation of fibroblasts in collagen matrices triggers ectocytosis of plasma membrane vesicles containing actin, annexins II and VI, and beta 1 integrin receptors. AB - To learn about the effects of tension on fibroblast function, we have been studying initial cellular responses to stress-relaxation. Human foreskin fibroblasts were cultured in anchored collagen matrices for 2 days, during which time mechanical stress developed. Subsequently, the matrices were dislodged; thereby allowing stress to dissipate. Within 5 min after initiating stress relaxation, fibroblasts retracted their pseudopodia. At this time, we observed the disappearance of cellular stress fibers and the formation of actin clusters along the cell margins. The actin was found to be located inside 200 nm diameter vesicles that were budding from the cell surface. Vesicles isolated from the matrix after stress-relaxation contained prominent 24 kDa, 36 kDa (doublet), 45 kDa, and 135 kDa polypeptides. The 45 kDa polypeptide was the major component in the Triton-insoluble vesicle fraction and appeared to be actin. The 36 kDa (doublet) polypeptide, which was found predominantly in the Triton-soluble vesicle fraction, was identified as annexin II. Vesicles also contained annexin VI and beta 1 integrin receptors but not tubulin, vimentin, vinculin or annexin I. The results suggest that stress-relaxation of fibroblasts induces a novel ectocytotic process involving transient budding of intact, plasma membrane vesicles from the cell cortex. On the basis of their morphological and biochemical features, these vesicles may be analogous to the 'matrix vesicles' released by chondrocytes and could play a role in extracellular matrix remodeling after wound contraction. PMID- 8360272 TI - Expression of integrin receptors and their role in adhesion, spreading and migration of normal human melanocytes. AB - Integrin receptors of human melanocytes in vivo and of melanocytes isolated and cultured from in vitro reconstituted normal human epidermis were investigated. Melanocytes were studied by high-resolution immunocytochemistry of in situ epidermis and were found to expose only the integrin subunits alpha 3, alpha 6, alpha v and beta 1 on their plasma membrane surface. Instead, cultured normal melanocytes expressed alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha v beta 3, which were immunoprecipitated from both metabolically and surface-labeled cells. Beta 1 integrins were diffused on the adhesion surface, while alpha v beta 3 was clustered in focal contacts both in control cells and upon dendrite induction with phorbol 12-myristate 13-acetate (PMA). The functional roles of integrins were studied in vitro by cell adhesion, spreading and migration assays. The sum of the data indicated that, in normal human melanocytes: (i) adhesion to defined substrata is mainly mediated by specific beta 1 integrins; (ii) spreading is mainly modulated by alpha v beta 3; (iii) the beta 1 and beta 3 heterodimers cooperate in regulating migration. The in vitro expression of two integrins (alpha v beta 3 and alpha 5 beta 1) that are not exposed in situ, and their role in the spreading and migratory properties of melanocytes, strongly suggest that they are involved in regenerating a normally pigmented epidermis during wound healing by controlling melanocyte spreading and migration over a provisional matrix. Tumor promoters, such as PMA, selectively increased the expression of alpha 3 beta 1. We suggest that this integrin might be involved in melanocyte migration on the newly formed basement membrane during wound healing as well as in intercellular recognition of adjacent keratinocytes. PMID- 8360273 TI - 5-Bromo-2-deoxyuridine regulates invasiveness and expression of integrins and matrix-degrading proteinases in a differentiated hamster melanoma cell. AB - Cell interactions with the extracellular matrix play a critical role in regulating complex processes such as terminal differentiation and tumor progression. In these studies we describe a melanoma cell system that should be useful in addressing the regulation of cell-matrix interactions and the roles they play in regulating differentiation and cell invasiveness. CS (suspension)-1 melanoma cells are relatively well differentiated: they are melanotic, responsive to melanocyte-stimulating hormone, and express TA99, a melanosome membrane differentiation marker. Their repertoire of integrin receptors for extracellular matrix ligands is limited; in particular, they lack receptors for vitronectin, accounting for the observation that they are nonadherent when cultured in the presence of serum. CS-1 cells are noninvasive as well, and express low levels of both metalloproteinases and activated plasminogen activators. Treatment of these cells with melanocyte-stimulating hormone causes them to increase melanin production and assume an arborized phenotype, suggesting that it promotes their further differentiation. In contrast, treatment of CS-1 with the thymidine analog 5-bromodeoxyuridine, converts them to a highly invasive cell population (termed BCS-1) that loses its differentiated properties and responsiveness to melanocyte stimulating hormone, acquires a broad integrin repertoire (including vitronectin receptors), and expresses elevated levels of metalloproteinases and activated urokinase. From these observations and findings of others on BrdU treatment of other developmental lineages, we hypothesize that BrdU both suppresses differentiation and promotes invasiveness of CS-1 cells. The demonstrated manipulability of CS-1 cells should make them extremely useful for studying the regulation of both terminal differentiation and tumor progression in the melanocyte lineage. PMID- 8360274 TI - Growth cone guidance and neuron morphology on micropatterned laminin surfaces. AB - Neurite growth cones detect and respond to guidance cues in their local environment that determine stereotyped pathways during development and regeneration. Micropatterns of laminin (which was found to adsorb preferentially to photolithographically defined hydrophobic areas of micropatterns) were here used to model adhesive pathways that might influence neurite extension. The responses of growth cones were determined by the degree of guidance of neurite extension and also by examining growth cone morphology. These parameters were found to be strongly dependent on the geometry of the patterned laminin, and on neuron type. Decreasing the spacing of multiple parallel tracks of laminin alternating with non-adhesive tracks, resulted in decreased guidance of chick embryo brain neurons. Single isolated 2 microns tracks strongly guided neurite extension whereas 2 microns tracks forming a 4 microns period multiple parallel pattern did not. Growth cones appear to be capable of bridging the narrow non adhesive tracks, rendering them insensitive to the smaller period multiple parallel adhesive patterns. These observations suggest that growth cones would be unresponsive to the multiple adhesive cues such as would be presented by oriented extracellular matrix or certain axon fascicle structures, but could be guided by isolated adhesive tracks. Growth cone morphology became progressively simpler on progressively narrower single tracks. On narrow period multiple parallel tracks (which did not guide neurite extension) growth cones spanned a number of adhesive/non-adhesive tracks, and their morphology suggests that lamellipodial advance may be independent of the substratum by using filopodia as a scaffold. In addition to acting as guidance cues, laminin micropatterns also appeared to influence the production of primary neurites and their subsequent branching. On planar substrata, dorsal root ganglion neurons were multipolar, with highly branched neurite outgrowth whereas, on 25 microns tracks, neurite branching was reduced or absent, and neuron morphology was typically bipolar. These observations indicate the precision with which growth cone advance may be controlled by substrata and suggest a role for patterned adhesiveness in neuronal morphological differentiation, but also highlight some of the limitations of growth cone sensitivity to substratum cues. PMID- 8360275 TI - Moesin, like ezrin, colocalizes with actin in the cortical cytoskeleton in cultured cells, but its expression is more variable. AB - The band 4.1 superfamily of proteins show approx. 30% sequence identity in their amino-terminal region to the membrane binding domain of erythrocyte band 4.1. Within this superfamily are three members, ezrin, radixin and moesin, that show approx. 75% overall sequence identity. A comparison of the domain structure and intracellular localization of ezrin and moesin in cultured cells is reported here. Limited proteolytic digestion of ezrin or moesin yields a relatively stable 32 kDa domain derived from the amino-terminal region that is homologous to the protease-resistant membrane binding domain of erythrocyte band 4.1. The remaining regions of the two proteins give rise to very different fragments, suggesting that the secondary/tertiary structures of the two proteins are different in these regions. We have generated polyclonal antibodies that discriminate between ezrin and moesin, and do not react with radixin. All cultured cell lines investigated contain ezrin, whereas moesin is variably expressed. Cells that contain both ezrin and moesin show a very similar pattern: both proteins are enriched and colocalize with actin in cell surface structures. Ezrin is also detected in the cytoplasm. In cells with few or no surface structures, both proteins show a patchy distribution in regions of the cell that contain fine networks of actin filaments. No staining of focal contacts or adherens junctions was observed. These results, together with those of others, lead to the conclusion that, of the members of this protein family, only radixin is an authentic component of adherens junctions and focal contacts. Ezrin and moesin are both found in cell surface structures after treatment of human A431 cells with epidermal growth factor, and ezrin, but not moesin, becomes phosphorylated on tyrosine. This study shows that ezrin and moesin have a similar subcellular distribution in cultured cells, yet are distinguishable in their expression, structure and ability to serve as a kinase substrate. PMID- 8360276 TI - Changing spatial patterns of DNA replication in the noise-damaged chick cochlea. AB - The purpose of the present study was to examine the spatio-temporal pattern of cell proliferation in the chick cochlea in response to the sensory hair cell loss induced by a 1.5 kHz pure tone at 120 dB SPL (1 dB = 20 muPa) for 48 h. DNA replication was evaluated with the bromodeoxyuridine (BrdU) pulse-fix technique. One group of birds was given multiple injections of BrdU (50 mg/kg) over a period of 8 h at various starting times during or after the exposure. Afterwards, their cochleas were removed and processed as whole mounts for BrdU immunohistochemistry. The cochleas of a second group of acoustically traumatized chicks were evaluated by scanning electron microscopy in order to determine the spatio-temporal pattern of hair cell loss. Hair cell loss was first observed 12 h after the start of the exposure and DNA replication started near the inferior edge of the hair cell lesion 24-32 h after the start of the exposure, i.e. 12-20 h after the first sign of hair cell loss. The site of hair cell loss and DNA replication shifted toward the superior edge of the basilar papilla as the exposure continued. The rate of DNA replication accelerated and reached its peak near the end of the 48 h exposure. The estimated latency of cell proliferation after hair cell loss was faster and the duration of DNA replication shorter than that observed in other sensory systems. The spatio-temporal pattern of DNA replication follows the spatio-temporal gradient of hair cell loss, suggesting that cell proliferation is triggered by hair cell loss itself rather than by intrinsic positional cues or gradients. PMID- 8360277 TI - The Drosophila melanogaster dodecasatellite sequence is closely linked to the centromere and can form connections between sister chromatids during mitosis. AB - We have used fluorescence in situ hybridisation to wild-type and rearranged mitotic chromosomes to map the Drosophila melanogaster dodecasatellite sequence. It is located at a unique site, within the pericentric heterochromatin of the right arm of the third chromosome, closely linked to the primary constriction. In polytene chromosomes, dodecasatellite is found as one or a few dots in the central region of the chromocentre. In untreated diploid cells, dodecasatellite sequences are found as one or two dots throughout the cell cycle. This distribution can be altered in a cell cycle-dependent manner in two ways. Firstly, in interphase cells, hypotonic shock promotes the decondensation of the genomic region containing this satellite, resulting in a string-like structure. Secondly, some of the precociously separated sister chromatids produced by colchicine treatment show dodecasatellite within the intervening space connecting the main dodecasatellite signals of each chromatid. The distribution of dodecasatellite seems to be rather constant between individuals of the same species, as indicated by the lack of any detectable variations in its pattern amongst individuals from six geographically distant strains of D. melanogaster. On the other hand, the distribution of dodecasatellite shows a remarkable degree of variation amongst closely related species of the melanogaster subgroup ranging from a non-detectable signal in Drosophila yakuba and Drosophila teissieri, to staining in the X, second and third chromososomes of Drosophila mauritiana. PMID- 8360278 TI - Interphotoreceptor retinoid-binding protein (IRBP), a major 124 kDa glycoprotein in the interphotoreceptor matrix of Xenopus laevis. Characterization, molecular cloning and biosynthesis. AB - We have demonstrated that the neural retina of Xenopus laevis secretes into the extracellular matrix surrounding the inner and outer segments of its photoreceptors a glycoprotein containing hydrophobic domains conserved in mammalian interphotoreceptor retinoid-binding proteins (IRBPs). The soluble extract of the interphotoreceptor matrix contains a 124 kDa protein that cross reacts with anti-bovine IRBP immunoglobulins. In vitro [3H]fucose incorporation studies combined with in vivo light and electron microscopic autoradiographic analysis, showed that the IRBP-like glycoprotein is synthesized by the neural retina and secreted into the interphotoreceptor matrix. A 1.2 kb Xenopus IRBP cDNA was isolated by screening a stage 42 (swimming tadpole) lambda Zap II library with a human IRBP cDNA under low-stringency conditions. The cDNA hybridizes with a 4.2 kb mRNA in adult Xenopus neural retina, tadpole heads as well as a less-abundant mRNA of the same size in brain. During development, IRBP and opsin mRNA expression correlates with photoreceptor differentiation. The translated amino acid sequence of the Xenopus IRBP clone has an overall 70% identity with the fourth repeat of the human protein. Sequence alignment with the four repeats of human IRBP showed three highly conserved regions, rich in hydrophobic residues. This focal conservation predicts domains important to the protein's function, which presumably is to facilitate the exchange of 11-cis retinal and all-trans retinol between the pigment epithelium and photoreceptors, and to the transport of fatty acids through the hydrophilic interphotoreceptor matrix. PMID- 8360279 TI - Characterization of a putative Drosophila GTP-binding protein. AB - We generated a set of monoclonal antibodies raised against Drosophila antigen eluted from a lectin affinity column. One antibody, mAb 13D5 recognizes an antigen found in the most dorsal regions of the ventral midline of Drosophila embryos at stages prior to and during axonogenesis. 13D5 recognizes cells dorsal to the ectoderm in the extended germ band beginning approximately 7 hours after fertilization and in the peripheral nervous system (PNS) at about 13 hours. In addition, 24-hour-old cultures of isolated embryonic neuroblasts possess a number of cells that express the 13D5 antigen and are not recognized by horseradish peroxidase antisera. These cells extend ramified processes with multiple growth cone-like structures or large individual processes with a broad growth cone structure. 13D5 immunoprecipitates a single band with an apparent molecular mass of 58 kDa and isolated a 1.9 kb EcoRI fragment from the lambda gt11 expression libraries. In situ hybridization to staged embryos using the digoxygenin-labeled probe reveals a pattern of expression in cells just lateral to the dorsal-most regions (mesectoderm) of the ventral midline in 8- to 9-hour embryos. In situ hybridization to cultured cells derived from whole embryos reveals several cell types with differing morphologies that express transcript recognized by the digoxygenin-labeled probe. These cells may possess either broad processes containing detectable transcript, or long thin processes with no detectable transcript. Northern analysis reveals a 2.1 kb RNA transcript detectable in all embryonic stages. Nucleotide sequence obtained from the 1.9 kb insert reveals homology with the GTP-binding regions of two signal recognition particle receptors (SNRP) isolated from canine and human tissues. PMID- 8360280 TI - Measurement of regional cerebral blood flow with positron emission tomography: a comparison of [15O]water to [11C]butanol with distributed-parameter and compartmental models. AB - To further our understanding of the best way to measure regional CBF with positron emission tomography (PET), we directly compared two candidate tracers ([15O]water and [11C]butanol, administered intravenously) and two popular implementations of the one-compartment (1C) model: the autoradiographic implementation representing a single PET measurement of tissue radioactivity over 1 min and a dynamic implementation representing a sequence of measurements of tissue radioactivity over 200 s. We also examined the feasibility of implementing a more realistic, and thus more complex, distributed-parameter (DP) model by assigning fixed values for all of its parameters other than CBF and tracer volume of distribution (Vd), a requirement imposed by the low temporal resolution and statistical quality of PET data. The studies were performed in three normal adult human subjects during paired rest and visual stimulation. In each subject seven regions of interest (ROIs) were selected, one of which was the primary visual cortex. The corresponding ROI were anatomically equivalent in the three subjects. Regional CBF, Vd, tracer arrival delay, and dispersion were estimated for the dynamic data curves. A total of 252 parameter sets were estimated. With [11C]butanol both implementations of the 1C model provided similar results (r = 0.97). Flows estimated using the 1C models were lower (p < 0.01) with [15O]water than with [11C]butanol. In comparison with the 1C model, the constrained version of the DP used in these studies performed inadequately, overestimating high flow and underestimating low flow with both tracers, possibly as the result of the necessity of assigning fixed values for all of its parameters other than CBF and Vd. PMID- 8360281 TI - Reproducibility of resting cerebral blood flow measurements with H2(15)O positron emission tomography in humans. AB - Two consecutive measurements of resting CBF were carried out in normal volunteers (n = 25) using H2(15)O positron emission tomography. Absolute whole-brain blood flow (WBBF; ml 100 g-1 min-1, mean +/- SD) for the first (40.3 +/- 6.4) and second (39.3 +/- 6.5) measurements was not significantly different (mean % difference 2.3 +/- 8.7). Analysis of regions of interest showed no significant differences in absolute regional CBF (rCBF) and normalized (rCBF/WBBF) rCBF. Left right differences were also not significant. These data demonstrate the reproducibility of resting CBF measurements in normal humans. PMID- 8360282 TI - Imaging ischemic tissue at risk of infarction during stroke. AB - Autoradiograms obtained after middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats show that the 99mTc complex of a 2-nitroimidazole derivatized propylene amine oxime (BMS-181321) is selectively retained in acutely ischemic brain before disruption of the blood-brain barrier (BBB), but not in the ischemic infarct. BMS-181321 is therefore a marker of ischemic tissue at risk of infarction and its uptake, unlike that of x-ray and magnetic resonance contrast agents, does not require disruption of the BBB. In keeping with this conclusion, we have found that the single-pass cerebral extraction fraction of BMS-181321 is 0.67 at normal rat whole-brain blood flow. Sequential single-photon emission computed tomographic images obtained from cats after MCAO show that the initial distribution of BMS-181321 approximates regional CBF and that selective retention subsequently produces a positive image within the ischemic territory. BMS-181321 is the first Tc complex able to indicate not only ischemia, but also ischemic tissue at risk of infarction. Use of this novel Tc complex to monitor biochemical events during ischemia may contribute to the clinical management of acute stroke. PMID- 8360284 TI - Acceleration of HSP70 and HSC70 heat shock gene expression following transient ischemia in the preconditioned gerbil hippocampus. AB - To evaluate the mechanism of tolerance to ischemia, inductions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs in gerbil hippocampus were compared with in situ hybridization between cases of a single 3.5-min period of forebrain ischemia and a 3.5-min period of ischemia 2 days after 2-min pretreatment with ischemia. Immunohistochemistry for HSP70 protein and morphological studies were also performed in the same brains up to 7 days after the reperfusion. Following a single 3.5-min period of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. However, the hippocampal CA1 cells produced only a minimum of HSP70 protein, and the cells were almost lost by 7 days. Following 3.5 min of ischemia after 2-min pretreatment, large populations of the CA1 cells survived at 7 days. The peak time of the HSP70 and HSC70 mRNA induction shifted to an earlier period of reperfusion in all hippocampal cells as compared with the case of a single episode of ischemia. The peak of HSP70 and HSC70 mRNA induction shifted from 1 day to 3 h in the CA1 cells. The CA1 cells produced strongly immunoreactive HSP70 from 3 hr to 2 days. These results suggest that pretreatment with an initial period of ischemia (for 2 min) accelerated HSP70 and HSC70 gene expression at the transcriptional level, ameliorated the translational disturbance of HSP70 mRNA to protein, and saved the CA1 cells from subsequent lethal ischemia (for 3.5 min). These changes of heat shock gene expression might play important roles in the acquisition of ischemic tolerance of hippocampal CA1 neurons. PMID- 8360283 TI - Local cerebral blood flow measured by xenon-enhanced CT during cryogenic brain edema and intracranial hypertension in monkeys. AB - We developed a closed-skull model of freeze injury-induced brain edema, a model classically thought to produce vasogenic edema, and observed the natural course of changes in edema and blood flow using xenon-enhanced computed tomography (CT) in five rhesus monkeys before and for up to 6 h post insult. Intracranial pressure (ICP) gradually rose throughout the duration of the experiment. CT scans and CBF images permitted direct observation of the evolution of the lesion and revealed early ischemia in the periphery of the injury zone that progressed over time in association with edema. Frequency histogram analysis of local CBF (ICBF) demonstrated subtle but potentially important changes in distribution of ICBF between and within hemispheres at various times post insult. Changes in ICBF distribution were phasic and dissociated from increases in ICP in the latter stages of injury. The Xe/CT CBF method can be used to evaluate the effects of injury and therapy on CBF in this and other models of acute brain injury. PMID- 8360285 TI - Biphasic striatal acetylcholine release during and after transient cerebral ischemia in gerbils. AB - Acetylcholine (ACh) release into the extracellular space was measured by HPLC with electrochemical detection after in vivo intracerebral microdialysis in the striatum of gerbils subjected to 15 min of bilateral carotid artery occlusion followed by 5 h of recirculation. Tissue ACh and choline (Ch) contents were also determined during ischemia and after 5, 30, 60, and 120 min of reflow. Fifteen minutes of ischemia led to a significant transient increase in extracellular ACh concentration (threefold after 7.5 min of ischemia) concomitant with a reduced endogenous ACh level (-62%) and increased tissue Ch content (ninefold). Recirculation significantly reduced the ACh release during the early period of reflow (-50% vs. basal level), followed by a significant increase in ACh release between 1 and 3 h of reflow (45-55% vs. basal level) and subsequent normalization. Simultaneously, a "rebound" of tissue ACh level occurred in the early period of reflow (fourfold vs. ischemic value), followed by gradual normalization after 2 h of reperfusion, whereas a rapid decrease in tissue Ch levels was found after 30 min of reflow. These findings represent the first demonstration of a biphasic release of ACh during ischemia and reperfusion, as assessed by intracerebral microdialysis in gerbils. PMID- 8360286 TI - Hypothermia attenuates the loss of hippocampal microtubule-associated protein 2 (MAP2) following traumatic brain injury. AB - Traumatic brain injury (TBI) produces a tissue-specific decrease in protein levels of microtubule-associated protein 2 (MAP2), an important cross-linking component of the neuronal cytoskeleton. Because moderate brain hypothermia (30 degrees C) reduces certain neurobehavioral deficits produced by TBI, we examined the efficacy of moderate hypothermia (30 degrees C) in reversing the TBI-induced loss of MAP2 protein. Naive, sham-injured, and moderate (2.1 atm) fluid percussion-injured rats were assessed for MAP2 protein content 3 h post injury using quantitative immunoreactivity measurements. Parallel groups of sham-injured and fluid percussion-injured animals were maintained in moderate hypothermia (30 degrees C), as measured by temporalis muscle temperature, for MAP2 quantitation 3 h post injury. No difference in MAP2 levels was observed between naive and sham injured normothermic animals. Hypothermia alone had no effect on soluble MAP2 levels in sham-injured animals compared with normothermic sham-injured controls (88.0 +/- 7.3%; p > 0.10). Fluid percussion injury dramatically reduced MAP2 levels in the normothermic group (44.3 +/- 5.9%; p < 0.0005) compared with normothermic sham-injured controls. No significant reduction of MAP2 was seen in the hypothermic injured group (95.2 +/- 4.6%; compared with hypothermic sham injured controls, p > 0.20). Although it is premature to infer any causal link, the data suggest that the attenuation of injury-induced MAP2 loss by hypothermia may contribute to its overall neuroprotective action. PMID- 8360287 TI - Secobarbital attenuates excitotoxicity but potentiates oxygen-glucose deprivation neuronal injury in cortical cell culture. AB - We examined the effects of secobarbital and other sedative-hypnotic barbiturates on the neuronal death induced by exposure to excitatory amino acids or deprivation of oxygen or glucose in mouse cortical cell cultures. N-Methyl-D aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate, and kainate toxicities were attenuated in a concentration-dependent fashion by high concentrations of secobarbital or thiopental. Antagonism of NMDA toxicity was not overcome by increasing NMDA concentration and not mimicked by gamma aminobutyrate. Despite these antiexcitotoxic actions, secobarbital exacerbated the neuronal death induced by deprivation of either glucose alone or oxygen and glucose together; death induced by oxygen deprivation alone was little affected. Thiopental and methohexital also increased oxygen-glucose deprivation injury. A possible explanation for this injury potentiation was provided by the observation that secobarbital enhanced the cellular ATP depletion induced by combined oxygen glucose deprivation. Deleterious effects on ATP production may counterbalance the protective effects of barbiturates under some conditions. PMID- 8360288 TI - Recovery of mitochondrial and plasma membrane function following hypoglycemic coma: coupling of ATP synthesis, K+ transport, and changes in extra- and intracellular pH. AB - The primary objective of the present study was to evaluate the recovery of plasma and mitochondrial membrane functions after 30 min of hypoglycemic coma and to establish whether a lingering accumulation of free fatty acids (FFAs) delays the recovery. A secondary objective was to study whether production of metabolic acids following glucose infusion leads to a fall in intracellular pH (pHi). Phosphocreatine, creatine, ATP, ADP, and AMP, as well as glycogen, glucose, lactate, pyruvate, and FFAs of rat brain cortex and caudoputamen were measured, and "free" ADP was calculated from the creatine kinase equilibrium. Extracellular pH (pHe) and K+ concentration (K+e) were measured with ion-sensitive microelectrodes, and pHi was derived by the CO2 method. Glucose injection was followed by resumption of oxidative phosphorylation within approximately 2 min and by an equally rapid restoration of normal K+e levels. These functions recovered although tissue FFAs remained elevated for at least 7-8 min. Tissue lactate content increased only moderately and production of metabolic acids did not lead to intracellular acidosis. After 15 min of recovery, pHi was moderately increased, although pHe fell toward 7.0. It is speculated that the dissociation between intra- and extra-cellular pH is compatible with an up-regulation of an Na+/H+ antiporter, e.g., by phosphorylation. PMID- 8360289 TI - Regulation of intracellular pH in single rat cortical neurons in vitro: a microspectrofluorometric study. AB - Intracellular pH (pHi) and the mechanisms of pHi regulation in cultured rat cortical neurons were studied with microspectrofluorometry and the pH-sensitive fluorophore 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein. Steady-state pHi was 7.00 +/- 0.17 (mean +/- SD) and 7.09 +/- 0.14 in nominally HCO3(-)-free and HCO3( )-containing solutions, respectively, and was dependent on extracellular Na+ and Cl-. Following an acid transient, induced by an NH1 prepulse or an increase in CO2 tension, pHi decreased and then rapidly returned to baseline, with an average net acid extrusion rate of 2.6 and 2.8 mmol/L/min, in nominally HCO3(-)-free and HCO3(-)-containing solutions, respectively. The recovery was completely blocked by removal of extracellular Na+ and was partially inhibited by amiloride or 5-N methyl-N-isobutylamiloride. In most cells pHi recovery was completely blocked in the presence of harmaline. The recovery of pHi was not influenced by addition of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or removal of Cl-. The rapid regulation of pHi seen following a transient alkalinization was not inhibited by amiloride or by removal of extracellular Na+, but was partially inhibited by DIDS and by removal of extracellular Cl-. The results are compatible with the presence of at least two different pHi-regulating mechanisms: an acid extruding Na+/H+ antiporter, possibly consisting of different subtypes, and a passive Cl-/HCO3- exchanger, mediating loss of HCO3- from the cell. PMID- 8360290 TI - An electron microscopic immunogold analysis of developmental up-regulation of the blood-brain barrier GLUT1 glucose transporter. AB - Electron microscopy was used to quantitate blood-brain barrier (BBB) glucose transporters in newborn, 14-day-old suckling, 28-day-old weanling, and adult rabbits. A rabbit polyclonal antiserum to a synthetic peptide encoding the 13 C terminal amino acids of the human erythrocyte glucose transporter (GLUT1) was labeled with 10-nm gold particle-secondary antibody conjugates and localized immunoreactive GLUT1 molecules in rabbit brain capillary endothelia. Three distinct populations of brain capillary profiles were identified in newborn rabbits: prepatent capillary buds, partially patent capillaries with highly amplified luminal membranes, and patent capillaries. Immunogold analyses indicated that the GLUT1 transporter abundance positively correlated with capillary developmental status. The mean number of gold particles per capillary profile increased at each developmental age examined, suggesting that developmental up-regulation of the BBB glucose transporter occurred in rabbits. GLUT1 immunoreactivity was three- to fourfold greater on the abluminal than luminal capillary membranes among all ages examined. Changes in the proportions of GLUT1 transporter were also seen, and possible reasons for the postnatal decrease in the percentage of cytoplasmic GLUT1 transporter are discussed. The numbers of cytoplasmic and membrane-associated immunogold particles increased with age. We conclude that regulatory modulations of BB glucose transport may be characterized by increases in BBB glucose transporter density with age and state of development. In addition, modulation of glucose transporter activity may be reflected by minor postnatal shifts of GLUT1 from cytoplasmic to membrane compartments, which can be demonstrated with quantitative immunogold electron microscopy. PMID- 8360291 TI - Tetrahydroaminoacridine and physostigmine increase cerebral glucose utilization in specific cortical and subcortical regions in the rat. AB - The effects of the anticholinesterases tetrahydroaminoacridine (THA) and physostigmine on local cerebral glucose utilization (LCGU) were studied in the conscious rat, using the autoradiographic [14C]deoxyglucose technique. THA (5 mg/kg i.p.) increased LCGU significantly in 8 of the 43 regions studied. A higher dose of THA (10 mg/kg) produced a metabolic activation in 19 of the 43 regions. LCGU increased in cortical areas (including parietal and temporal cortices), the septohippocampal system, the thalamus, the lateral habenula, the basolateral amygdala, the superior colliculus, and the substantia nigra. Scopolamine (4 mg/kg i.p.) reversed the THA-induced LCGU increase. Physostigmine (0.2 and 0.5 mg/kg) increased LCGU in 15 and 22 regions, respectively. The average magnitude of the change induced by 0.5 mg/kg of physostigmine was similar to that observed after THA at 10 mg/kg, but the topography of the effects was somewhat different. Physostigmine increased LCGU in the preoptic magnocellular area, the brainstem, and the cerebellum but not in the parietal cortex. The effects in the septohippocampal system were smaller than those induced by THA. The regional topography of the LCGU increase overlapped the distribution of the M2 muscarinic receptors and that of acetylcholinesterase activity. These data suggest that the major effects of THA and physostigmine on LCGU result from their anticholinesterase action. PMID- 8360292 TI - Perivascular microapplication of endothelin-1: a new model of focal cerebral ischaemia in the rat. AB - In the present study, we describe the effects of perivascular microapplication of the potent vasoconstrictor peptide endothelin-1 (ET-1; (120 pmol in 3 microliters), delivered via a guide cannula stereotaxically positioned above the left cerebral artery (MCA) of the conscious male Sprague-Dawley rat. Ten minutes after the administration of Et-1, mean arterial blood pressure had increased by 20% and profound reductions in local cerebral blood flow (up to 93%) were observed within those brain areas supplied by the MCA. In addition, significant increases in local cerebral blood flow were observed within the globus pallidus (100%), substantia nigra pars reticulata (48%), ventrolateral thalamus (65%), and dorsal hippocampus (74%) ipsilateral to the insult. Twenty-four hours following the insult, the pattern of ischaemic damage was similar to that reported previously following permanent occlusion of the rat MCA. It is suggested that perivascular microapplication of Et-1 may provide a useful model for the study of the functional disturbances associated with focal cerebral ischaemia in the conscious rat. PMID- 8360293 TI - A model of brain arteriolar oxygen and carbon dioxide transport during anemia. AB - Existing experimental and theoretical evidence suggests that precapillary diffusion of O2 and CO2 occurs between arterioles and tissue under normal physiologic conditions. However, limited information is available on arteriolar gas transport during anemia. With use of a mathematical model of an arteriolar network in brain tissue, anemic hematocrits of 35, 25, and 15% were modeled to determine the effect of anemia on the exchange, the change in the equilibrium tissue O2 and CO2 tensions, and the increase in blood flow needed to restore tissue oxygenation. We found that the blood PO2 exiting the network fell from 66 mm Hg normally to 48 mm Hg during the severest anemia. Concurrently, the equilibrium tissue O2 tensions dropped from 44 to 23 mm Hg. For CO2 the exit blood PCO2 was 58 mm Hg for a 15% hematocrit, an increase of 4 mm Hg from the normal value, and equilibrium tissue PCO2 increased from 56 to 61 mm Hg. Blood flow increases from normal values necessary to offset the effects of the decreased O2 delivery to the tissue were 26, 86, and 222%, respectively, for hematocrits of 35, 25, and 15%. We compared our model results with recent experimental studies that have suggested that the amount of O2 diffusion is much higher than predicted values. We found that these experimental O2 gradients are three to four times larger than theoretical. PMID- 8360295 TI - Dynamic high-resolution MR imaging of brain deoxygenation during transient anoxia in the anesthetized rat. AB - Transient alterations in brain oxygenation during 60-s periods of anoxia were visualized at high spatial resolution (voxel size < or = 0.15 microliter) with the use of serial long echo time FLASH (fast low-angle shot) magnetic resonance images (measuring time > or = 6 s) of halothane-anesthetized rats in vivo. Difference images from normoxia and anoxia exploit the signal decrease associated with increased levels of paramagnetic deoxyhemoglobin in the arterial and venous blood pool. Insights into the spatial heterogeneity of oxygen deprivation are complemented by physiologic information from the time course of pertinent signal changes in different regions of the brain. PMID- 8360294 TI - Striatal 18F-dopa uptake: absence of an aging effect. AB - L-[18F]6-Fluoro-DOPA (L-[18F]6-fluoro-3,4-dihydroxyphenylalanine; FDOPA) has been used with quantitative positron emission tomography (PET) to assess presynaptic nigrostriatal dopaminergic function in life. The relationship of estimated kinetic rate constants for striatal FDOPA uptake [Ki(FDOPA)] to the normal aging process has been the subject of conflicting reports. Resolution of this issue has been hampered by methodological differences in previous FDOPA/PET investigations. We studied 19 healthy normal subjects (aged 27-77 years) and measured striatal Ki (FDOPA) according to each of the earlier methods. While significant correlations (p < 0.005) existed between Ki(FDOPA) values estimated by the various techniques, none correlated with normal aging. We conclude that normal striatal Ki(FDOPA) values estimated using quantitative FDOPA/PET are uncorrelated with the aging process. PMID- 8360296 TI - Changes in insulin-like growth factor 1 receptor density after transient cerebral ischemia in the rat. Lack of protection against ischemic brain damage following injection of insulin-like growth factor 1. AB - Binding of 125I-insulin-like growth factor-1 (125I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA1 and CA3 regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intracerebroventricular injections of IGF-1 (2 micrograms) prior to and after transient cerebral ischemia did not reduce neuronal damage. The increased up regulation on IGF-1 receptors and the absence of neuroprotection by IGF-1 suggest that the intracellular signal transduction chain activated by the IGF-1 receptor may be interrupted. PMID- 8360297 TI - Chromatographic techniques used to determine benz[c]acridines in environmental samples. AB - Benz[c]acridine and many of its related compounds have been shown to exhibit carcinogenic activity. Unfortunately, these compounds are continually being found in many natural and environmental samples in widely divergent geographical locations. A review of chromatographic methods for mainly benz[c]acridine and its analogues is presented. PMID- 8360298 TI - Detection of airborne cocaine and heroin by high-throughput liquid-absorption preconcentration and liquid chromatography-electrochemical detection. AB - A high-throughput liquid-absorption preconcentrator (HTLAP) for rapid and/or ultrasensitive detection and analysis of trace contaminants samples air at a rate of 600-700 l/min and collects analytes from vapors or aerosols at an efficiency of 40-60% into a small volume of liquid absorbent dripping at a rate of 0.1-2 ml/min. These features combine to reduce the lower detection limit (LDL) of available analytical instrumentation by a factor of > 1000 and/or to permit faster sampling and far more rapid on-site air monitoring than were previously practicable. LDLs of ca. 1:10(13) (v/v) of alkaloids have been achieved with LC and electrochemical detection. The HTLAP is directly adaptable to most liquid phase analyzers. The small rate of liquid collection is also compatible with available interfaces to mass spectrometers. Moreover, the HTLAP permits detection and quantitation of polar or highly reactive compounds that cannot be readily analyzed by conventional preconcentration and GC. PMID- 8360299 TI - Pollutants in drinking water and waste water. AB - Extracts of drinking water and effluents from municipal and industrial sewage treatment plants were analysed by gas chromatography-mass spectrometry and by high-performance liquid chromatography combined with ultraviolet and/or mass spectrometric detection. After column chromatography or flow-injection analysis bypassing the analytical column, ionization was performed by a thermospray interface. Identification of the pollutants was carried out by tandem mass spectrometry, generating daughter-ion spectra by collision-induced dissociation. Most pollutants in drinking water and in the effluents of waste water treatment plants are surface-active compounds of anthropogenic origin or their biochemical degradation products. Difficulties encountered during separation, detection and identification are presented and discussed and techniques for solving these problems are proposed. PMID- 8360300 TI - Comparison of the abundance of the fecal sterol coprostanol and fecal bacterial groups in inner-shelf waters and sediments near Sydney, Australia. AB - Concurrent measurement of the sewage tracer coprostanol and fecal indicator bacteria were made for water and sediments collected in January 1992 from coastal waters off Sydney, Australia. The coprostanol results were compared with data from an earlier survey conducted in 1989 before the commisioning of Sydney's deepwater ocean outfalls in 1990 and 1991. Good correlations were observed for both water and sediment samples between coprostanol and the two fecal indicator organisms, fecal coliforms and Clostridium perfringens spores, thereby validating the use of coprostanol as a sewage signature in this environment. For sediments, most inner-shelf sites (1-10 km offshore) showed an increase in the concentration of coprostanol between the two surveys. The areas of highest concentration have been shifted further off-shore, to zones adjacent to the diffusers. PMID- 8360301 TI - Solid-phase extraction followed by high-performance liquid chromatographic analysis for monitoring herbicides in drinking water. AB - A multiresidue analytical method based on C18 solid-phase extraction and one-run HPLC determination has been developed for the analysis of eleven acidic, neutral and weak basic herbicides in drinking water. A 1-1 sample of water was preconcentrated by passage through a 500-mg C18 solid phase extraction column. The retained compounds were eluted from the column with 1 ml of methanol. After concentration of the extract the pesticides were separated and quantified by reversed-phase HPLC with UV detection. Bentazone, 2,4-D, MCPA, fluazifop-acid, metoxuron, monolinuron, metobromuron, diuron, linuron, atrazine and simazine were determined simultaneously in a single run on a C18 HPLC column. Reanalyses of the sample extracts on a second cyano column were used to confirm the identity of the neutral and basic compounds. The limit of determination, defined as four times the baseline noise, varied between 0.01 microgram/l and 0.1 microgram/l depending on the compound, the detection sensitivity of the instrument and the type of HPLC column used. PMID- 8360302 TI - Chromatographic methods in the determination of herbicide residues in crops, food and environmental samples. AB - The state of the art of chromatographic methods used in the determination of herbicide residues in crops, food and environmental samples is reviewed. The main structural groups of herbicides, i.e., triazines, phenyl- and sulphonylureas, carbamates, uracils and phenoxyalkanoic and arylphenoxypropanoic acids, and important degradation products (dealkylated triazines, substituted anilines, chlorophenols) are considered. Advantages and drawbacks of gas (GC), liquid (LC) and thin-layer chromatography in this type of analysis are discussed. The characteristics of a modern chromatographic method for the determination of herbicide residues are summarized and trends in the development and combination of current GC and LC methods discussed. PMID- 8360303 TI - High-performance liquid chromatographic analysis of carbofuran residues in tomatoes grown in hydroponics. AB - Tomato plants grown in hydroponics were irrigated three times on alternate days with nutrient solutions fortified with carbofuran at levels of 36, 111 and 222 mg 1-1, and carbofuran residues were analysed in tomato fruits. Residues were found to be below the maximum residue level set up by Codex Alimentarius Mundi (0.1 mg kg-1) 6, 11 and 18 days after the third irrigation with nutrient solutions fortified with carbofuran. Consequently, the withholding period of 60 days may be reduced to allow continuous harvest of tomatoes under the conditions used in this experiment. PMID- 8360304 TI - Application of solid-phase partition cartridges in the determination of fungicide residues in vegetable samples. AB - Disposable, ready-to-use cartridges filled with a macroporous diatomaceous material are used to extract in a single step fungicide residues with dichloromethane from aqueous acetone extracts of vegetables. This procedure takes the place of some functions (such as separating funnel partition, drying over anhydrous sodium sulphate and clean-up) usually performed by separate steps in classical schemes. Fourteen fungicides (dichloran, vinclozolin, chlorthalonil, triadimefon, dichlofluanide, procymidone, hexaconazole, captan, folpet, ditalimfos, iprodione, captafol, pyrazophos and fenarimol) were determined using the described procedure with recoveries between 83 and 107% at spiking levels ranging for the different compounds from 0.04 to 0.40 mg/kg. Crops subjected to the described procedure included lettuce, strawberry, apple, yellow pepper and peach, and gave extracts containing a mass of co-extractives between 5 and 30 mg. Compared with classical schemes, the described procedure is simple, less labour intensive, allows parallel handling of several extracts and does not require preparation and maintenance of equipment. Troublesome emulsions such as those frequently observed in separating funnel partitioning do not occur. PMID- 8360305 TI - Liquid chromatographic analysis of antibacterial drug residues in food products of animal origin. AB - This paper reviews recent developments in the liquid chromatographic (LC) methods of analysis for the residues of antibiotics (aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, macrolides, beta-lactams, etc.) in food products of animal origin. The review also covers clean-up procedures, such as, ultrafiltration, liquid-liquid partition, solid-phase extraction, immunoaffinity, and matrix solid-phase dispersion, for use as extraction, deproteination, and concentration steps. The LC methods offer considerable potential for rapid automated analysis, and some may be used as direct screening for residues in meat and milk. PMID- 8360306 TI - Organic micropollutants in Swiss sewage sludge. AB - Sludges from sixteen municipal and eleven industrial Swiss sewage treatment plants were analysed for adsorbable organic compounds (AOX), chlorinated pesticides, polychlorinated biphenyls and polycyclic aromatic hydrocarbons. Except for the AOX values, which were significantly higher (p < 0.05) in industrial sludges, there was no significant difference between industrial and municipal sludges. The AOX values did not correlate with any of the measured pollutants. The methods employed (capillary GC-MS and GC-electron-capture detection) proved to be suitable for monitoring organic micropollutants in industrial and municipal sewage sludges. PMID- 8360307 TI - Chromatographic determination of volatile solvents and their metabolites in urine for monitoring occupational exposure. AB - The determination of volatile solvents and their metabolites in biological materials such as expired air, blood or urine allows the estimation of the degree of exposure of these chemicals. Chromatographic methods are now universally employed for this purpose and numerous analytical procedures are available for the determination of the most commonly used volatile solvents and their metabolites in urine. GC methods appear well adapted to the determination of the parent volatile solvents in blood and urine and may be used for the determination of their urinary metabolites, but these methods often require several prechromatographic steps. However, HPLC is becoming a powerful tool for the accurate and easy determination of urinary metabolites of volatile solvents, considering its decisive advantages for routine monitoring. Further, recent developments in HPLC could widen the usefulness of this method for most complex analytical problems that could be encountered during this measurement. However, despite the relative neglect of planar chromatography in this area of concern and considering the great interest in methods that could permit the simultaneous assay of numerous samples often required by routine monitoring, new approach using improved methods such as overpressured TLC could be very fruitful in the future. PMID- 8360308 TI - Environmental analysis of polychlorinated terphenyls: distribution in shellfish from the Ebro Delta (Mediterranean). AB - Polychlorinated terphenyls (PCTs) have characteristics almost identical with those of polychlorinated biphenyls (PCBs) and have been used for analogous applications, but only sporadic reports of the occurrence of PCTs in the environment have been published. High-resolution gas chromatography with electron capture detection (HRGC-ECD) and mass spectrometric detection in the selected ion monitoring mode was used to analyse samples for PCTs. The homologue distribution of Aroclor 5432, 5460, Leromoll 141 and the PCTs in samples of shellfish from the Ebro Delta (Catalonia, Spain) was established, taking into account the contribution of the [M-Cl2]+ fragments. Quantification was achieved by HRGC-ECD. Concentrations were between 790 and 3 ng/g (dry mass). PMID- 8360309 TI - Rapid isolation of polychlorinated biphenyls from milk by a combination of supercritical-fluid extraction and supercritical-fluid chromatography. AB - The extraction and isolation of polychlorinated biphenyls (PCBs) from sample matrices such as freeze-dried milk is a lengthy and expensive process that conventionally requires the isolation of microgram amounts of PCBs from large volumes of flammable organic solvents used in the extraction and chromatographic stages. Supercritical-fluid extraction (SFE) and chromatography (SFC) using carbon dioxide has been investigated as a replacement procedure using a Simplex optimisation approach to optimise the working conditions. The SFE conditions required to extract PCBs and milk fat from freeze-dried milk were investigated, and it was found that although extraction was rapid (10 min), the conditions required were identical so that there was no separation of PCBs and fat. However, SFC conditions have been developed that permit the resolution of PCBs from milk fat in 15 min. Thus, a combination of SFE and SFC have the potential to replace the existing methods of extraction and isolation with procedures that are quicker, cheaper, and avoid the use of flammable organic solvents. PMID- 8360310 TI - Determination of paraquat in rat brain by high-performance liquid chromatography. AB - The applications of a method based on ion-pair solid-phase extraction and reversed-phase HPLC are reported. The method was used to measure paraquat concentrations in discrete brain areas at different times after its systemic administration in rats. In addition, the method was employed in the determination of paraquat levels in whole-brain samples from rats of various ages systemically treated with several doses of the herbicide. PMID- 8360311 TI - Study of polychlorinated dibenzodioxins and furans from municipal waste incinerator emissions in The Netherlands: analytical methods and levels in the environment and human food chain. AB - An overview is given of the methods that have been used in the study of polychlorodibenzo-p-dioxins and polychlorodibenzofurans in agriculture and the human food chain in a national survey and monitoring programme, including sampling strategies, sampling in the field and clean-up and analysis in various biological and environmental samples by high-resolution gas chromatography-high resolution mass spectrometry. The quality of data was evaluated as a result of internal quality control protocols and participation in interlaboratory comparison studies. Statistical analysis techniques and modelling were applied in order to compare and relate congener profiles in various matrices and to evaluate levels found in field studies for their use for regulatory purposes. PMID- 8360312 TI - Detection of human T-cell lymphotropic virus type 1 infection by the polymerase chain reaction using dried blood specimens on filter papers. AB - A simple method for detection of proviral DNA sequences of human T-cell lymphotropic virus type 1 (HTLV-1) was developed using dried blood specimens on filter papers. The whole blood was blotted onto the Guthrie paper. After the blood has dried, the blotted paper was punched out into small discs. The discs were then boiled to prepare the template for PCR (filter paper-PCR method). The filter paper-PCR method detected even a single HTLV-1-infected cell in three discs. The sensitivity of the filter paper-PCR method was equivalent to that of the method in which DNA was extracted with phenol and used as the template for PCR (DNA extraction-PCR method). In addition, DNA in the blotted filter paper was still utilizable as the template after the storage at 25 degrees C for at least 7 wk. A total of 53 clinical specimens from 30 seropositive and 23 seronegative individuals who were screened by particle agglutination (PA) test were analysed for HTLV-1 DNA by both PCR methods. Of 30 PA-positive specimens, 28 were also positive for HTLV-1 antibody by Western blot (WB) analysis, but two were indeterminate. The twenty eight WB-positive and one of the two indeterminate specimens were positive for HTLV-1 proviral DNA by both PCR methods. Of 23 PA negative specimens, 22 were negative for HTLV-1 proviral DNA by both PCR methods. However, one PA-negative specimen was positive by both PCR methods. This patient was a 16-mth-old infant who was born to an HTLV-1 carrier mother and fed thereafter without her breast milk. In comparison to DNA extraction-PCR method, the sensitivity and specificity of the filter paper-PCR method was 100%, respectively. PMID- 8360313 TI - Specific detection of anti-HBc antibodies with an enzyme immunoassay using recombinant HBcAg and monoclonal antibodies. AB - An enzyme immunoassay for the detection of total anti-HBc antibodies in undiluted serum samples was developed. This assay utilizes an anti-HBc monoclonal antibody and a recombinant HBc antigen. The results of the clinical validation are now reported. A total of 1,301 sera were tested using both the Recombinant TOTAL HBc Ab EIA and a reference assay. The specificity was evaluated on a panel of 573 normal human sera and human sera from subjects with pathological findings unrelated to a hepatitis B virus infection. The sensitivity was studied on a total of 455 sera from HBV infected patients at different stages of infection. The final results indicate 99.8% sensitivity and 99.8% specificity. In addition, 273 sera with either isolated anti-HBc antibodies or with anti-HCV antibodies were tested. The agreement between the Recombinant and the reference assay for these two populations, 96.6 and 90.1%, respectively, is discussed. PMID- 8360314 TI - Concentration of fish enveloped viruses from large volumes of water. AB - The validity of several concentration procedures for the detection of fish enveloped viruses present in large volumes of water was determined. Viral haemorrhagic septicaemia virus (VHSV) was used to evaluate adsorption/elution to positively-charged MK filter cartridges for the concentration of enveloped viruses. For fresh water, the efficiency of the procedure ranged from 12 to 100%, with a mean recovery of 57%. In seawater samples, the recoveries varied from 15 to 100%, with a mean recovery of 59%. The same virus was used in methods such as organic flocculation and ammonium sulphate flocculation with very poor recoveries of infectious virus, caused by the inactivation of VHSV in both procedures. Concentration of seawater samples from tanks housing sea bass or gilthead affected by viral erythrocytic infection and lymphocystis, respectively, were carried out. In both cases, the viruses responsible for the outbreaks were detected by electron microscopy in the concentrated water samples. PMID- 8360315 TI - Immuno disc assay for screening duck hepatitis B surface antigen in serum, liver tissue and cultured hepatocytes. AB - An immuno disc assay (IDA) for semi-quantitative analysis of the surface antigen (DHBsAg) of duck hepatitis B virus (DHBV) is described. Unpurified antigen preparations were adsorbed onto punched-out nitrocellulose membrane discs. Rabbit antiserum raised against serum-derived gradient-purified DHBsAg was used for detecting the antigen. Cross-reacting antibodies in the rabbit antiserum were removed using normal duck serum and normal duck hepatocytes. The sensitivity of the IDA was compared with that of the Western blot analysis and was observed to be of the same order, but differed slightly for DHBsAg in liver and sera. In contrast to Western blot analysis, antigen specificity for the IDA included the S protein. Immunodetection was carried out in microtitre plates, but the procedure was accelerated by attaching the antigen-adsorbed discs to an adhesive plate sealer. The IDA was exemplified for measuring DHBsAg in duck serum, duck liver homogenates and viral protein synthesis in cultures of DHBV-infected hepatocytes. PMID- 8360316 TI - Rapid production of full-length, infectious geminivirus clones by abutting primer PCR (AbP-PCR). AB - The application of the polymerase chain reaction (PCR) method of DNA amplification for the isolation of full-length, infectious clones of geminiviruses is described. Non-overlapping, abutting 20-mer oligonucleotide primers were used to produce a linear product from the circular geminivirus genomic template. Clones of African cassava mosaic virus (ACMV) DNA A, obtained by this method, were infectious following mechanical inoculation (in the presence of ACMV DNA B) onto Nicotiana benthamiana. Normal ACMV symptoms resulted and typical geminate viral particles were detected by electron microscopy. The use of PCR for the detection and production of full-length, infectious geminivirus clones is discussed. PMID- 8360317 TI - Improved specificity of testing methods for filovirus antibodies. AB - An epizootic among monkeys imported into the United States created an immediate need for detection of antibodies to filoviruses. Thousands of samples were submitted to the Centers for Disease Control and Prevention for testing. Problems of sensitivity and specificity existed in the methods available for these assays. The experiments described in this report resulted in improved methods for the detection of antibodies to filoviruses, both for indirect fluorescent antibody assays (IFA) by standardizing methods and the Western blot (WB) by minimizing antigen load and by incorporating skim milk in diluents. PMID- 8360318 TI - Incorporation of microinjected biotin-labelled actin into nascent myofibrils of cardiac myocytes: an immunoelectron microscopic study. AB - Incorporation of microinjected biotin-labelled actin into nascent myofibrils of cultured cardiac muscle cells was investigated by immunogold electron microscopy. At the proximal parts of myofibrils, gold labelling was first found (at about 4 min after injection) around the A-band level. This observation suggests that polymerization of actin or the addition of newly-formed actin filaments occurs preferentially in association with myosin filaments to increase the myofibrillar girth. The distal terminals of developing myofibrils were also labelled at about 4 min after injection. This rapid incorporation of actin subunits at the myofibrillar ends suggests the continued reorganization and/or de novo formation of myofibrils at these positions. Along the extending direction of the myofibrillar terminals, gold particles were arranged in rows on the inner surface of the sarcolemma. These rows of particles continued to become longer with incubation. It appears that actin subunits are added at the membrane-associated ends of pre-existing actin filaments to increase the length of myofibrils. PMID- 8360319 TI - The complex Young's modulus of skeletal muscle fibre segments in the high frequency range determined from tension transients. AB - Stiffness measurements of muscle fibres are often based on application of a length change at one end of the muscle fibre and recording of the following tension change at the other end. In this study a method is developed to determine in the high frequency range (up to 40 kHz) the complex Young's modulus of skeletal muscle fibre as a function of frequency from the tension transient, following a rapid stepwise length change completed within 40 microseconds. For this purpose both a new mechanical moving part of the displacement generating system and a force transducer with a high natural frequency (70 kHz) had to be developed. In addition to stiffness measurements of a silk fibre to test the displacement generating system and the method of analysis, stiffness of skeletal muscle fibres in relaxed and rigor state have been measured. The complex Young's moduli of relaxed muscle fibres as well as muscle fibres in rigor state are frequency dependent. In both cases the complex Young's modulus increases smoothly with increasing frequency over a range of 250 Hz up to 40 kHz. The phase angles of the responses remained almost constant at a value of 0.3 radians for a fibre in rigor and 0.6 radians for a relaxed fibre. This leads to the conclusion that for muscle fibres in rigor state the recovery in the tension response to a step length change shows a continuous distribution of relaxation times rather than a few discrete ones. Results of our stiffness measurements are compared with results obtained from current viscoelastic models used to describe stiffness of muscle fibre in this frequency range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360320 TI - Two-dimensional time-resolved X-ray diffraction studies of live isometrically contracting frog sartorius muscle. AB - Results were obtained from contracting frog muscles by collecting high quality time-resolved, two-dimensional, X-ray diffraction patterns at the British Synchrotron Radiation Source (SERC, Daresbury, Laboratory). The structural transitions associated with isometric tension generation were recorded under conditions in which the three-dimensional order characteristic of the rest state is either present or absent. In both cases, new layer lines appear during tension generation, subsequent to changes from activation events in the thin filaments. Compared with the 'decorated' actin layer lines of the rigor state, the spacings of the new layer lines are similar whereas their intensities differ substantially. We conclude that in contracting muscle an actomyosin complex is formed whose structure is not like that in rigor, although it is possible that the interacting sites are the same. Transition from rest to plateau of tension is accompanied by approximately 1.6% increase in the axial spacing of the myosin layer lines. This is explained as arising from axial disposition of the interacting myosin heads in the actomyosin complex. Model calculations are presented which support this view. We argue that in a situation where an actomyosin complex is formed during contraction, one cannot describe the diffraction features as being either thick or thin filament based. Accordingly, the layer lines seen during tension generation are referred to as actomyosin layer lines. It is shown that these layer lines can be indexed as submultiples of a minimum axial repeat of approximately 218.7 nm. After lattice disorder effects are taken into account, the intensity increases on the 15th and 21st AM layer lines at spacings of approximately 14.58 and 10.4 nm respectively, show the same time course as tension rise. However, the time course of the intensity increase of the other actomyosin layer lines and of the spacing change (which is the same for both phenomena) shows a substantial lead over tension rise. These findings suggest that the actomyosin complex formed prior to tension rise is a non-tension generating state and that this is followed by a transition of the complex to a tension-generating state. The intensity increase in the 15th actomyosin layer line, which parallels tension rise, can be accounted for assuming that in the tension-generating state the attached heads adopt (axially) a more perpendicular orientation with respect to the muscle axis than is seen at rest or in the non tension-generating state. This suggests the existence of at least two structurally distinct interacting myosin head conformations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360321 TI - Models of the mechanism for crossbridge attachment in smooth muscle. AB - The mechanism responsible for formation of attached, dephosphorylated crossbridges (latchbridges) in smooth muscle is controversial. Myosin light chain phosphorylation may be obligatory for crossbridge attachment; if this were the case, latchbridges would arise solely by dephosphorylation of attached, phosphorylated crossbridges. Alternatively, the presence of attached crossbridges could induce cooperative activation by allowing dephosphorylated crossbridges to attach to the thin filament. We evaluated whether four-state models based on dephosphorylation and/or cooperativity-regulated attachment could quantitatively predict smooth muscle contractile behaviour. Five quantitative models for transitions between crossbridge states were developed. Mechanisms for latchbridge formation included: (1) dephosphorylation, (2) cooperativity-regulated attachment dependent only on attached, phosphorylated crossbridges, (3) cooperativity regulated attachment dependent on all attached crossbridges, (4) dephosphorylation and cooperativity-regulated attachment dependent only on attached, phosphorylated crossbridges, and (5) dephosphorylation and cooperativity-regulated attachment dependent on all attached crossbridges. All five models approximated the time course of contraction and the dependence of steady-state stress on myosin phosphorylation in the swine carotid artery. In the two models that had cooperative attachment regulated by all attached crossbridges, small increases in the rate constant for cooperativity-regulated attachment resulted in positive feedback and irreversible contraction. We suggest that a number of four-state crossbridge models can predict contractile behaviour in arterial smooth muscle. Potentially, latchbridges could be formed by both dephosphorylation and cooperativity-regulated attachment. If cooperativity regulated latchbridge attachment does exist in smooth muscle, we suggest that it should be dependent only on the number of phosphorylated crossbridges rather than all attached crossbridges. PMID- 8360322 TI - Mechanical response to photolytic ATP pulses of skinned muscle fibres pre activated with a small pulse of ATP. AB - (1) Skinned fibres from rat psoas muscle were placed in oil and activated at 10 degrees C by pulse photolysis of caged ATP. From the force and stiffness transients on small ATP pulses, we estimated the concentration and rate of ATP hydrolysis of the crossbridges in the fibres. They were 0.14 mM and 0.16 mMs-1, respectively, and thus the turnover rate was 1.1 s-1. (2) To examine the mechanical properties of the physiological ADP-bound crossbridges, we took a double-pulse protocol: the skinned fibre was first activated with a conditioning ATP pulse (0.2-0.5 mM). Several (3-5) seconds later, when almost all the ATP should have been hydrolysed into ADP+P(i), we applied another ATP pulse (0.2-1 mM) to test the fibre. (3) An analysis of the transients on the test pulses indicated that the conditioning pulse slowed the rate of crossbridge detachment. The time course of force development was thus expected to be also delayed, but was not. (4) We suggested that the rigor crossbridge might differ from the nucleotide-free intermediate in the physiological reaction cycle. PMID- 8360324 TI - Abstracts of the 1992 Annual Meeting on Muscle and Cell Motility Physiology. Tokyo, 18-19 December 1992. PMID- 8360323 TI - Partial titin cDNA sequence isolated from rabbit cardiac muscle RNA. AB - Two regions of the rabbit cardiac titin cDNA were amplified from rabbit cardiac muscle total RNA using primers based on rabbit skeletal muscle titin (connectin) cDNAs. These 1.7 kb and 1.5 kb RNA-PCR products were based on the 3' regions of the skeletal muscle titin clones CE12 and MS2, respectively. The cDNA sequence of the 1.7 kb product was extended an additional 1.5 kb by a novel 3' extension technique which used random primers in RNA-PCR. The cardiac titin cDNAs were 99% identical in nucleotide sequence to their skeletal muscle counterparts and predicted two types of 100-residue repeats. Southern blot analysis suggested that both cardiac and skeletal titin are encoded by the same gene. PCR amplification of human genomic DNA with titin specific primers indicated that there is strong sequence similarity between rabbit and human titin sequences. The successful amplification of a 907 basepair region from human genomic DNA suggested that titin contains large exons which span multiple motif borders. This may be particularly advantageous in the processing of such a large RNA transcript. PMID- 8360325 TI - Gangliosides and bacterial toxins in Guillain-Barre syndrome. AB - Autoimmune factors are strongly favoured as mediating Guillain-Barre syndrome (GBS); however, the precise mechanisms by which this occurs remain unknown. Microbial infections in a susceptible host resulting in an idiosyncratic immune response which cross-reacts with nerve constituents still remains the most plausible working hypothesis on which much current research is based. Considerable recent evidence indicates that this humoral immune response is at least in part directed to gangliosides. Interestingly, many bacterial toxins, including botulinum and tetanus neurotoxins, also bind to gangliosides and induce diseases with some similarities to GBS. This article discusses the evidence in favour of a pathogenic role for anti-ganglioside antibodies in GBS in the context of our knowledge of the biology of gangliosides and the factors that determine their immunogenicity. PMID- 8360326 TI - Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. AB - Interferons (IFN) are biological molecules with anti-viral, anti-proliferative and immunomodulatory actions. There is evidence that IFN-gamma increases the frequency of exacerbations of multiple sclerosis (MS) whereas IFN-beta may reduce their frequency. Here we present evidence that IFN-beta significantly decreases concanavalin A (Con A)-induced proliferation of peripheral blood mononuclear cells (PBMC) of MS patients and healthy individuals. Similar results were obtained when PBMC were activated through the T cell receptor (TcR) by anti-CD3 monoclonal antibody or independently of it by phorbol ester and Ca2+ ionophore. These effects of IFN-beta were also noted when IFN-gamma and IFN-beta were added together. Furthermore, IFN-beta decreased proliferation when added to cells that were already pre-activated. Activated CD4+ and CD8+ T cells were downregulated to approximately the same extent. Analysis of cytokine production showed that IFN gamma production by Con A activated PBMC was increased in MS when compared to controls. IFN-beta significantly decreased IFN-gamma production in MS patients and control individuals. Con A activated cultures treated with IFN-beta showed decreased IL2R expression and accumulation of IL2. These results show that IFN beta decreases T cell activation and IFN-gamma production in vitro, effects that may be beneficial in MS. PMID- 8360327 TI - Investigation of a synthetic peptide as immunogen for a variant epidermal growth factor receptor associated with gliomas. AB - We have previously demonstrated antibody production to a glioma-associated variant form of the human epidermal growth factor receptor in rabbits that had received a synthetic peptide mimicking the unique primary structure of the variant protein as immunogen. We report here the response of mice, rabbits, goats, and macaques immunized by various protocols to this peptide. Titers to both peptide- and cell-elaborated variant receptor were measured, and the capacity to recognize the variant receptor in human tumor samples was determined. Within the range of species and strains investigated, we demonstrated a variable species-associated response to the peptide (rabbits > mice > goats > rats > macaques). Rabbits and a single goat produced specific, high titer antibody activity to the variant receptor protein following immunization with peptide alone. Murine titers to the parent protein were not appreciable following peptide immunization alone; additional immunization with variant receptor as expressed on cell membranes was used to boost this response. PMID- 8360328 TI - Trans-blood-brain-barrier albumin leakage and comparisons of intrathecal IgG synthesis calculations in multiple sclerosis patients. Multiple Sclerosis Study Group, Alpha Interferon Study Group, and Azathioprine Study Group. AB - We compared four equations for estimating intrathecal IgG synthesis (Tibbling and Link IgG index (T/L), Schuller and Sagar (S/S), Reiber and Felgenhauer (R/F), and Tourtellotte (T) equations) using data from chronic progressive MS patients. For normal albumin leakage (AL) (< 75 mg/day-intact BBB), T (r = 0.15) and R/F (r = 0.10) showed comparable positive correlations with trans-BBB AL, T/L (r = -0.10) was negative and S/S was uncorrelated (r = 0.05). For abnormal AL (> or = 75 mg/day), the R/F (r = -0.24), S/S (r = -0.37) and the T/L (r = -0.22) equations overcorrected, whereas the T (r = 0.07) equation values did not correlate with AL. The albumin index and trans-BBB albumin leakage rate formulae gave essentially identical estimates of BBB leakage (r = 0.99, P = 0.0001). We conclude that in chronic progressive MS patients the R/F, T/L and S/S formulae overcompensate for large abnormal T-BBB albumin leakage rates. The T formula corrected best for IgG transudate at high AL rate values in MS. PMID- 8360329 TI - Magnetic resonance imaging investigation of blood-brain barrier damage in adoptive transfer experimental autoimmune encephalomyelitis. AB - Recent advances in fast magnetic resonance imaging (MRI) techniques have allowed quantification of parameters such as T1 relaxation time, which can be modified by changes in the water content of a tissue. We have used this new method to study the evolution of blood-brain barrier (BBB) changes after adoptive transfer of MBP specific (AT-EAE) and ovalbumin-specific T cell lines in Lewis rats. Measurable changes in T1 relaxation time suggesting widespread increase in BBB permeability were found, starting on day 3 post inoculation (p.i.), in the midbrain and brainstem of AT-EAE rats. In addition, we noted a significant decrease in T1 relaxation time before injection of a paramagnetic agent, in the cisternal cerebrospinal fluid (CSF) of diseased animals, starting on day 5 p.i. In vitro measurement of T1 in CSF containing various concentrations of albumin, IgM and glucose showed that, at physiological concentrations, a T1 decrease is mainly associated with an increase in albumin concentration. A moderate increase in BBB and blood-CSF barrier permeability was found as early as 4-8 h p.i., in rats injected with MBP-specific as in animals injected with ovalbumin-specific T cell lines, suggesting a non-specific mechanism. Experimental MRI may become a powerful tool to sequentially analyse changes in barrier dynamics, for example following pharmacological intervention. PMID- 8360330 TI - On classification of post-mortem multiple sclerosis plaques for neuroscientists. AB - Plaque classification is proposed based on observation of 348 plaques from 52 post-mortem multiple sclerosis (MS) cases. Four plaque types, ranging from 'earliest lesion' to 'inactive', are described according to immunological activation and degree of demyelination, seen by expression of the Major Histocompatibility Complex (MHC) Class II molecule, HLA-DR, and by Oil Red O staining, respectively. 40% of the plaques were inactive. This result highlights the need for a description of plaque activity for studies of the etiopathogenesis of MS; that is, the earliest and/or the most active plaques should contain the causative agent whereas the burnt out plaques should not. PMID- 8360331 TI - Trafficking of activated cytotoxic T lymphocytes into the central nervous system: use of a transgenic model. AB - We have used cell or tissue-specific promoters to express lymphocytic choriomeningitis virus (LCMV) proteins in selected cells in independent lines of transgenic mice. Upon adoptive transfers into these mice, MHC-restricted LCMV specific cytotoxic T lymphocytes homed specifically to either the choroid plexus (SV40 promoter) or beta cells of the islets of Langerhans (rat insulin promoter). The availability of promoters specific for neurons, oligodendrocytes and astrocytes makes this approach compelling for evaluating T cell trafficking into the CNS and for analyzing antigen presentation in vivo in the CNS. PMID- 8360332 TI - Minor myelin proteins can be major targets for peripheral blood T cells from both multiple sclerosis patients and healthy subjects. AB - T cell recognition of myelin is likely to play a role in the pathogenesis of multiple sclerosis. Predominant protein components of myelin, myelin basic protein (MBP) and proteolipid protein (PLP), have been considered as possibly relevant autoantigens, especially since both proteins are encephalitogenic in various laboratory animals. It has remained unclear, however, to what extent the numerous minor proteins contained in myelin may serve as targets for human T cell responses to myelin. In this study, the abilities of several minor myelin proteins to trigger proliferative responses of human peripheral blood T cells were compared to that of MBP. By using a water soluble collection of myelin proteins as an antigen, including MBP as the major component, short-term T cell lines were generated. Proliferative responses were determined against the various proteins after their fractionation by HPLC. Short-term T cell lines from both multiple sclerosis patients and healthy control subjects displayed significant responses to several minor myelin proteins but failed to respond to MBP. Only the use of purified MBP as trigger antigen allowed the selective expansion of MBP specific T cell lines. These findings indicate that minor myelin proteins may act as relevant targets for autoreactive human T cells. PMID- 8360333 TI - Differential effect of interleukin-1 beta on Ia expression in astrocytes and microglia. AB - In an earlier study we demonstrated the inhibitory effect of interleukin-1 beta (IL-1 beta) on human leukocyte antigens (HLA) class II enhancement by interferon gamma (IFN-gamma) in a human glioblastoma multiforme cell line. In this study we have examined the effect of IL-1 beta on IFN-gamma induced major histocompatibility complex (MHC) class II (Ia) in primary cultures of newborn murine astrocytes and microglial cells. Astrocytes expressed very low levels of Ia molecules under basal culture conditions but these molecules could be induced with IFN-gamma. IL-1 beta in doses ranging from 1 to 100 units/ml inhibited the level of IFN-gamma induced Ia expression on astrocytes, and this inhibition was dose-dependent (mean maximum inhibition of 53 +/- 5% in number of positive cells and 53 +/- 2.6% in mean fluorescence intensity in four separate experiments). IL 1 beta treatment had no effect on MHC class I induction by IFN-gamma in the astrocytes. In contrast, microglial cells expressed Ia molecules under basal culture conditions, and this expression was enhanced by IFN-gamma treatment. Both basal and IFN-gamma induced Ia expression on microglia were resistant to IL-1 beta treatment in doses ranging from 1 to 100 units/ml. These results indicate that Ia expression is differentially regulated on astrocytes and microglial cells and that IL-1 beta may have an important immune regulatory function in the central nervous system. PMID- 8360334 TI - Orthodontist of the year. PMID- 8360335 TI - Dr. Lysle E. Johnston, Jr., on orthodontics and the scientific method, an interview by Dr. White. PMID- 8360336 TI - Bond strengths and fracture modes of three orthodontic adhesives. PMID- 8360338 TI - Predictable indirect bonding. PMID- 8360337 TI - Use of mutual protective agreement after a heart attack. PMID- 8360339 TI - Bringing an ectopic lower canine into the arch. PMID- 8360340 TI - Double ball clasp for plate and splint appliances. PMID- 8360341 TI - A computer in the hand. PMID- 8360342 TI - Orthodontic office design: applications of glass block. PMID- 8360343 TI - Sealing palatal expansion screws with light-cured adhesive. PMID- 8360345 TI - Macintosh program for submitting TMD insurance claims. PMID- 8360344 TI - Comparison of three dry-heat convection sterilizers. PMID- 8360346 TI - Teamwork, quality, and competitive advantage: the Deming philosophy in orthodontics. PMID- 8360347 TI - Rubber dam isolation of the working field in orthodontics. PMID- 8360348 TI - Tooth extrusion with a removable appliance. PMID- 8360349 TI - Comparative three-dimensional analysis of CT-scans of the calvaria and cranial base in Apert and Crouzon syndromes. AB - The purpose of this study is to describe and analyze Apert and Crouzon skulls from three-dimensional (3-D) reconstructions of CT-scans. 12 Apert patients and 19 with Crouzon syndrome were included in the study. The age range was 0 to 23 years. All CT-scannings were carried out according to the same protocol with a slice thickness of 2 or 4 mm and 3-D reconstructions of the craniofacial region included midsagittal and horizontal cuts. A number of qualitative characteristics of the calvaria and cranial base were recorded and the cranial base angle was measured on the 3-D models. Our results showed that Apert and Crouzon syndromes are very different in cranial development and their dysmorphology is highly age dependent. We suggest that cartilage abnormalities, especially in the anterior cranial base, play a primary role in cranial development in the Apert syndrome from very early intrauterine life. Several cranial anomalies observed postnatally, however, are caused by the resultant dysmorphic and compensatory growth and are probably compounded by early cranial deformation. The primary abnormality in Crouzon syndrome appears to be premature fusion of sutures and synchondroses. Based on the findings at birth and early infancy it would seem that such fusions occur relatively late in fetal life. The adult cranial form in Crouzon's patients is explainable by resultant dysmorphic and compensatory growth changes. Very early release of the coronal suture areas with advancement of the frontal bone is advocated in both syndromes but for somewhat different reasons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360350 TI - Median cleft of the lower lip, mandible and manubrium. A case report. AB - There is a wide variation in the severity of median clefts of the lower lip and mandible. We report a severe case demonstrating clefts of the lower lip and mandible together with lack of supporting structures in the neck and upper sternum. Since a case with a cleft of the manubrium sterni is very rare, the literature is reviewed and discussed. PMID- 8360351 TI - Fibrin sealing and histometrical changes in conventionally sutured microvascular anastomoses. AB - Reports from the literature demonstrated an early occlusive thrombosis rate of microvascular anastomoses of up to 25%. In order to reduce free flap failure due to kinking and pressure in the region of the anastomosis, fibrin sealing of microvascular anastomosis was recommended in previous studies. However, it is well accepted that haemostasis is activated by vascular wall injuries (lesions of the endothelial layer). For that reason, a fast re-endothelialisation of the inner surface of the anastomosis is thought to reduce early occlusive thrombosis and, subsequent, free flap failure. To clarify whether application of fibrin adhesives exert any effect on microvascular anastomoses, we constructed 84 anastomoses in rat arteries applying sealant or non-sealant in randomized order. At certain time intervals, arteries operated on were removed and histologically analyzed. Early complete endothelial regeneration, 4 days after surgery, was observed in the unsealed anastomosis group, whereas sealed anastomosis showed a complete re-endothelialisation only after 7 days. These observations may be explained by a reduced multiplication rate and migration speed (0.3 mm/day) of endothelial cells during the first 3 days (unsealed anastomosis: 0.63 mm/day). In addition, in sealed anastomoses a higher incidence of media necrosis was found (60.7% vs 49.3% in the unsealed group). These histological changes were confirmed by scanning and transmission electron microscopy. PMID- 8360352 TI - The mandibular body bone (MBB) graft: an alternative source of membranous bone. AB - The use of mandibular body bone (MBB) as an alternative source of membranous bone graft is described. The MBB technique is a simple, safe and rapid method of obtaining cortical bone for grafting. Furthermore MBB is membranous bone, which has been reported to be more dimensionally stable after grafting than is endochondral bone. The donor site is more readily accessible than is that for cranial bone, the other source of membranous bone. Two 1.5 x 3 cm rectangular grafts are generally available. We recommend the use of MBB in situations where the technique provides sufficient bone. PMID- 8360353 TI - Solitary plasmacytoma of the mandible. Case report and review of the literature. AB - A case of solitary plasmacytoma of the mandible is presented. Review of the literature disclosed the following characteristics regarding the clinical course and prognosis. The patients ages ranged from 34 to 76 years, with a mean of 53 years; there was a marked preponderance of males. The site of predilection was the posterior portion of the mandible. The common symptom was a non-painful swelling of the mandible of long duration, and radiological features were non specific. Monoclonal immunoglobulin was initially detected in 42% of the evaluated patients. The majority of patients were treated with radiation therapy with a mean dose of 48Gy with or without surgery. The period of follow-up ranged from 4 months to 12 years, and 17% of the patients progressed to multiple myeloma within 1 year. PMID- 8360354 TI - Morphological study of the parotid lymph nodes. AB - The surgical resection of metastatic lesions of the parotid gland is controversial. The present anatomical study has been carried out to determine whether or not lymph nodes are present in the deep lobe of the gland and to assess their number in different age groups. We found a substantial number of lymph nodes in the deep lobe of the parotid gland independently of the subject's age. It can be concluded that from a strictly morphological point of view, superficial parotidectomy does not appear adequate when radical neck dissection including the parotid gland is to be done. PMID- 8360355 TI - The treatment of mandibular fractures in children. AB - 92 children with mandibular fracture were treated at our hospital between 1980 and 1989. Distribution and treatment of the fractures focus on a new classification based upon the stage of the dentition, site of the fracture and displacement of the tooth-bearing part of the mandible. The treatment rationale includes intermaxillary fixation by specially designed mini-arch bars with acrylic resin stiffening in cases with undisplaced fractures in the early stages of the dentition. With the help of this technique, invasive procedures for fracture immobilization become less common. The indication for miniplate osteosynthesis is limited to displaced or multiple fractures of the tooth-bearing part of the mandible. The combination of miniplates and monomaxillary splinting with mini-arch bars allows a shorter duration of intermaxillary fixation and hence early functional treatment of additional condylar fractures. Correctly applied miniplates neither injure the tooth germs nor lead to growth disturbances of the mandible. The classification and treatment of mandibular fractures in children are discussed. PMID- 8360356 TI - The split rib bundle graft in mandibular reconstruction by M. el Sheikh--Vol. 20 (1992) 326-332. PMID- 8360357 TI - Evaluating diagnostic tests in dentistry. PMID- 8360358 TI - Characterization of Actinomyces with genomic DNA fingerprints and rRNA gene probes. AB - Cellular DNA from 25 Actinomyces naeslundii and Actinomyces viscosus strains belonging to the 7 taxonomic clusters of Fillery et al. (1978) and several unclustered strains was obtained by enzymatic and N-lauroylsarcosine/guanidine isothiocyanate treatment of whole cells, followed by extraction of the nucleic acid. The DNA samples were digested with restriction endonucleases BamHI or PvuII, and agarose gel electrophoresis was used to obtain DNA fingerprints. The DNA fragments were subjected to Southern blot hybridization with a digoxigenin labeled cDNA probe transcribed from Escherichia coli 16S and 23S rRNA. The patterns of bands from genomic (DNA fingerprints) and rDNA fingerprints (ribotypes) were used for comparison between the taxonomic cluster strains and strains within clusters. Representative strains from each taxonomic cluster provided different BamHI DNA fingerprints and ribotype patterns with 3 to 9 distinct bands. Some strains within a cluster showed identical ribotype patterns with both endonucleases (A. naeslundii B120 and A. naeslundii B102 from cluster 3), while others showed the same pattern with BamHI but a different pattern with PvuII (A. naeslundii ATCC 12104 and 398A from cluster 5). A viscosus ATCC 15987 (cluster 7) and its parent strain T6 yielded identical fingerprint and ribotype patterns. The genomic diversity revealed by DNA fingerprinting and ribotyping demonstrates that these techniques, which do not require phenotypic expression, are suited for study of the oral ecology of the Actinomyces, and for epidemiological tracking of specific Actinomyces strains associated with caries lesions and sites of periodontal destruction. PMID- 8360359 TI - In vitro demineralization by strains of Actinomyces viscosus and Streptococcus sobrinus of sound and demineralized root surfaces. AB - Root sections were inoculated with one of two strains of Actinomyces viscosus or a strain of Streptococcus sobrinus and then incubated for 9 days in Trypticase soy broth (TSB) containing 0.25% glucose or TSB supplemented with 0.25% sucrose (TSB+S). Lesion progression was measured from microradiographs. One section from each group was examined with a transmission electron microscope. Lesion progression was associated with a fall in the pH of the medium. However, lesion progression was not correlated with the mean 48-hour pH of the medium. In both TSB and TSB + S, lesion progression with A. viscosus was significantly greater than in the S. sobrinus group. However, the mean 48-hour pH value in TSB + S was lower than that in the S. sobrinus group. Plaque formation in TSB was, subjectively, least in the S. sobrinus group. Examination of transmission electron micrographs revealed bacteria penetrating the surfaces of the sections and extending into the lesion in the A. viscosus groups but not in the S. sobrinus group. This in vitro bacterial plaque model of root caries may be suitable for investigations of the bacterial etiology of root-surface caries and the virulence factors associated with pathogenicity. PMID- 8360360 TI - Protective effect of topically applied fluoride in relation to fluoride sensitivity of mutans streptococci. AB - The aim of the present in vitro experiments was to determine whether the protection of enamel by topically applied fluoride against demineralization by bacterial acids would depend on the fluoride sensitivity of the bacteria. Glucose agarose gel suspensions of fluoride-sensitive and fluoride-resistant mutans streptococci were placed on bovine enamel specimens with different amounts of fluoride. One group of specimens was untreated, a second group had been pretreated with a F-lacquer, and a third group had been pretreated with the F lacquer and rinsed subsequently with a KOH-solution, to remove deposited CaF2. After 22-hour incubations at 37 degrees C, the amounts of calcium and lactate and the pH of the agarose gels were determined. This procedure was repeated on three consecutive days. Two parent S. mutans strains, one parent S. sobrinus strain, and five fluoride-resistant derivatives were tested. Both pretreatments gave a significant protection to the enamel specimens. For the S. mutans strains, the degree of protection did not depend on the fluoride sensitivity of the strains. For the S. sobrinus strains, the results suggested a reduced protection against demineralization by the fluoride-resistant derivatives. Only from the second group of enamel specimens was enough fluoride released for inhibition of bacterial metabolism. Presumably, it was released by the dissolution of CaF2. It is concluded that a possible adaptation of mutans streptococci in dental plaque to frequent exposures to fluoride will not necessarily decrease the caries preventive effects caused by topically applied fluoride agents. PMID- 8360361 TI - The isolation and characterization of milleri group streptococci from dental periapical abscesses. AB - Reports of the isolation of streptococci from dental abscesses have shown an association of the "S. milleri" group with such lesions. There has been considerable confusion regarding the taxonomy of these organisms, but the milleri group has recently been reclassified into three distinct species: Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius. In this study, 45 samples from dental periapical abscesses were examined. Milleri group streptococci were isolated from 16 patients (37%), 15 being identified as S. anginosus and one as S. intermedius. In one patient, S. anginosus was isolated in pure culture, and it would appear that this is the predominant species of milleri group streptococci associated with periapical abscesses. PMID- 8360362 TI - Long-term effects of Meridol and chlorhexidine mouthrinses on plaque, gingivitis, staining, and bacterial vitality. AB - The aim of the present study was to compare the effect on plaque growth and gingival response of Meridol, an amine/stannous fluoride solution, during a three month investigation, with those of a placebo preparation as a negative control and a chlorhexidine solution as a positive control, in a double-blind study. After having their teeth professionally cleaned, 36 volunteers continued their usual oral hygiene for a period of two weeks. Their teeth were then polished again (month 0) after which they rinsed twice daily (morning and evening) with one of the three mouthrinses in addition to their habitual toothcleaning. After three months of rinsing, plaque indices remained lowest in the chlorhexidine group, although the subjects using Meridol had indices significantly lower than those of individuals rinsing with the placebo solution. The gingival index scores in the Meridol group were higher than in the chlorhexidine group and lower than in the placebo group. The plaque vitality scores showed a bactericidal effect in vivo with chlorhexidine and Meridol during the entire experiment. The use of Meridol resulted in more toothstaining than with the placebo, but significantly less than with chlorhexidine. This study demonstrated that Meridol reduced plaque accumulation, retarded gingivitis development, possessed a definite bactericidal action, and produced only slight toothstaining. PMID- 8360363 TI - Recovery of the jaw-opening reflex after lesions of the lingual nerve in the rat. AB - In three groups of rats, lesions were produced in the right lingual nerves near the base of the tongue; the three types of injury inflicted (cryogenic, crush, and stretch) are reputed to spare the epineurium but produce different degrees of intraneural damage. In regular assessments of recovery, an electrical stimulus (sufficient to elicit the jaw-opening reflex) was applied to either side of the tongue in turn; the amplitude of the reflex was measured as the isometric force of jaw opening. The size of the reflex response to stimulation of the injured side was followed up to 4 months post-lesion, with the response elicited from the control side used as the reference level. The reflex was absent when the experimental side was stimulated immediately after creation of a lesion; the first sign of reflex recovery was found at about 15 days post-operative. Subsequently, in 84% of the animals, the reflex activity elicited from the experimental side increased until it exceeded that elicited from the reference side; this relative hyperreflexia started 1-4 months post-lesion and had a highly variable duration. There was no difference in the incidence, latency, or duration of the hyperreflexia following any of the three types of lesion. The hyperreflexia found in this study is not readily explained by existing hypotheses of the mechanisms underlying post-lesion hyperesthesia or central neuronal hyperexcitability. PMID- 8360364 TI - Spatial and gender-dependent variations in perioral pinprick sensitivity. AB - Twenty-eight right-handed young adults participated in a sensory testing experiment to evaluate pinprick sensitivity at ten spatially matched sites on the right and left sides of the face. Stimuli were provided by a sharp-pointed dental explorer on which a rubber eraser had been positioned to minimize variations in the extent to which the skin was indented. Sharpness was defined as the magnitude at which abrupt, localized pricking/stinging sensations were evoked. A magnitude matching procedure was used to reduce among-subject variability in the data. Specifically, each estimate of sharpness was adjusted (i.e., divided) by the subject's mean estimate of the brightness of a visual stimulus. Prior to data collection, subjects were carefully instructed on the use of a common numerical scale for assignment of values of sharpness and brightness. Repeated-measures analysis of variance of the adjusted estimates of sharpness revealed a non significant effect of gender (p > 0.4), a highly significant effect of side (p < 0.0001), and a highly significant effect of test site (p < 0.0001). Pinprick percepts were sharper on the left side of the face than on the right. Moreover, the vermilion of the upper lip exhibited the greatest sensitivity to pinprick; the vermilion of the lower lip exhibited the least sensitivity. These results suggest that use of a patient's sensitivity to pinprick during clinical neurosensory examination must be undertaken in an informed manner. A conclusion of pathological alteration in sensation can be made only after consideration of the normal spatial variations in the percept of sharpness. PMID- 8360365 TI - The reinnervation of healing extraction sockets in the ferret. AB - The objective of this study was to describe the pattern of healing of pulpal and periodontal nerve fibers following tooth extraction. The mandibular canine teeth were, under general anesthesia, removed from one side of nine young ferrets. One week (two animals), one month (four animals), and three months (three animals) later, again under general anesthesia, the animals were perfused with fixative. The mandibles were decalcified, paraffin-embedded, and serially sectioned. Sample sections were stained with hematoxylin and eosin, the remainder with a silver stain for nerves. Serial reconstructions were made of the innervation in control teeth and in the extraction sockets. A grid sampling technique was used for the estimation of the innervation density in different regions at various levels in the healing socket. One week after extraction, although osteoid material was beginning to fill the socket, the pattern of innervation remained similar to that of controls in being restricted to the former location of the periodontal ligament and being densest in the apical third of the socket. One month after extraction, the innervation consisted of many fine axons or small bundles distributed throughout the healing osteoid tissue though still most dense in the periphery of the socket. The overall innervation density increased between one week and one month post-extraction. At three months, as the margins of the socket were becoming obscured, the innervation consisted largely of one or two organized nerve trunks running from the apical to the coronal aspect in either the central or lateral aspects of the socket. At no time was there evidence of neuroma formation. PMID- 8360366 TI - Differences in composition of cell-attachment sialoproteins between dentin and bone. AB - Matrices of dentin and bone were compared with respect to the content of cell attachment sialoproteins. The levels of two sialoproteins, osteopontin (OPN) and bone sialoprotein (BSP), were determined in dentin and bone by immunochemical procedures. Polyclonal antibodies against bovine BSP and an antibody against the amino-terminal decapeptide of rat OPN were used. The relative levels of OPN and BSP in dentin were less than one-tenth of the levels in bone. The differences between dentin and bone levels of OPN and BSP were thus larger than those for osteonectin or bone Gla protein in the two tissues. The scarcity of the cell attachment proteins in dentin may reflect the metabolic inactivity of dentin. PMID- 8360367 TI - Development of the human submandibular salivary gland. AB - The development and morphogenetic timetable of the submandibular gland was studied in 37 human embryos and human fetuses. The medial paralingual groove constituted the anlage of the submandibular gland: Its anterior three-quarters gave rise to Wharton's duct, and its posterior quarter to the submandibular gland proper. The sublingual process of the submandibular gland originated from a lateral ectodermal bud of the anlage of the submandibular gland, in the posterior quarter of the medial paralingual groove. PMID- 8360368 TI - Nucleolar organizer regions as markers of incipient cellular alterations in squamous epithelium. AB - Transcriptionally active nucleolar organizer regions identified by silver staining (AgNOR) vary in number with cellular activity and/or malignant transformation and have been used as a diagnostic tool. A morphometric study of AgNORs was performed in an experimental model of irradiated squamous epithelium (Wistar rat sole skin) 4, 8, and 14 hours and 1, 2, 5, and 7 days post irradiation with 50 Gy of x-rays. A statistically significant and progressive rise in AgNOR average volume of up to 238% and reduction in AgNOR number/nucleus of up to 40% were detected as a function of post-irradiation time. A statistically significant 46% increase in AgNOR volume was detected as early as 8 h post-irradiation, when no histological changes were observable in routine preparations. These results suggest that AgNORs may be useful as a quantitative marker of incipient changes in cellular activity and caution against the indiscriminate use of AgNORs in the follow-up of lesions which may have been exposed to radiotherapy. Furthermore, this study suggests the possibility of using AgNORs as a sensitive biological dosimeter in cases of uncontrolled exposure to radiation. PMID- 8360369 TI - Coping with oral surgery by self-efficacy enhancement and perceptions of control. AB - Recent work has suggested that patients' coping could be improved in stressful dental situations if perceptions of self-efficacy and control could be enhanced. To test this hypothesis, 70 first-time third-molar extraction patients were randomly assigned to one of four surgery preparation conditions: standard preparation, oral premedication, relaxation, and a relaxation+efficacy-enhancing feed-back condition in which subjects were given false galvanic skin response (GSR) biofeedback leading them to believe that they were highly skilled at relaxing. Analyses indicated that: (1) all treatments were seen as equally credible (controlling for placebo effects); (2) a priori contrasts showed that both the relaxation-only treatment and the relaxation+efficacy-enhancement treatment were superior to the premedication and standard preparations in raising coping self-efficacy; (3) regardless of treatment condition, increase in reported coping self-efficacy was significantly correlated with pre-operative anxiety, with self-reported peri-operative distress, and with behavioral ratings of peri operative distress; and (4) the relaxation treatments resulted in lower pre operative anxiety than the other interventions, and linear contrasts showed significant trends in which the relaxation+efficacy-enhancing condition was superior to the relaxation-only condition, which was in turn superior to the medication condition and the standard preparation in reducing both pre-operative anxiety and behavioral ratings of peri-operative distress. It was concluded that thoughts related to self-confidence and control can be manipulated, and that these thoughts can in part determine how well a person copes in stressful dental situations. PMID- 8360370 TI - Analysis of debond rates of resin-bonded prostheses. AB - Debonding rates of 164 resin-bonded prostheses (RBP) placed from 1974 to 1985 were examined at recall. The yearly debond rates were calculated, the cumulative probability of failure was determined for the debonded RBPs, and Weibull distribution parameters were determined. For perforated prostheses, there was a high initial debond rate, followed by slowly decreasing rates for about 5 years. Increasing rates after 5 years indicated the beginning of wear-out. The Weibull parameters for the wear-out period of the perforated prostheses were: characteristic life = 128 (SE = 2) months, modulus = 1.27 (0.06), and threshold parameter = 0. Data were available for etched frameworks for 6 years and showed decreasing debond rates during this time. The characteristic life of the etched bridges was 318 (84) months. The cumulative failure data were also modeled with a cubic polynomial distribution that resulted in a U-shaped hazard function. PMID- 8360371 TI - Mechanical performance of a dental composite: probabilistic failure prediction. AB - In clinical situations, the mechanical performances of dental structures--for example, composite restorations--depend on many factors. Most of them have a probabilistic character. Because composites are brittle materials, their strength should also be considered as a probabilistic quantity. For successful prediction of mechanical failure of structures consisting of these materials, a probabilistic approach is indispensable, and a suitable definition of equivalent stress must be introduced. An equivalent stress facilitates the transfer of strength data of laboratory specimens to situations where the stress state is much more complicated. The tensile and compressive strengths of composites differ considerably. Of two equivalent stress definitions that potentially describe this experimental fact (the Drucker-Prager and the Modified von Mises equivalent stress), the predictive capacity was investigated for a microfine composite. In a probabilistic approach to failure, use of the Drucker-Prager equivalent stress appeared to be superior, because the average failure load of notched beams was predicted with an error smaller than 8%. PMID- 8360372 TI - Release of fluoride and other elements from light-cured glass ionomers in neutral and acidic conditions. AB - The purpose of this study was to measure the release of fluoride, sodium, silicon, calcium, strontium, and aluminum from light-cured glass ionomers. The materials tested were: (1) Baseline VLC thick mix; (2) Baseline VLC thin mix; (3) Fuji Lining LC; (4) Vitrebond; and (5) XR-Ionomer. A conventional glass ionomer, Ketac-FilAplicap, and a silver-reinforced glass ionomer, Ketac-Silver, were used as controls. Each test specimen was first stored for 16 days in de-ionized water, followed by a further 16 days in 0.01 mol/L lactic acid (pH 4.0); both solutions were replaced at predetermined intervals. After that, the specimens were immersed for up to 122 days in de-ionized water. During the immersion, light-cured glass ionomers showed considerable variation in the release of fluoride and other elements. In lactic acid, all cements eluted the matrix-forming cations, aluminum and calcium or strontium. This suggests that light-cured materials are as equally susceptible to erosion as are chemically cured glass ionomers. During the immersion, some of the light-cured materials showed a considerable weight gain. PMID- 8360373 TI - The balance between quality and quantity. PMID- 8360374 TI - Perceptions of dental fluorosis. AB - Mild dental fluorosis has long been accepted as a side-effect of water fluoridation and, more recently, has been recognized as a consequence of the use of other fluoride-based caries-preventive strategies. Traditionally, dental health professionals have not seen this as being of public health importance, but members of the public have not been asked their opinion. The purpose of the present study was to gather the opinions of lay groups concerning the appearance of the teeth of children with various degrees of fluorosis. Twenty-eight children, born in 1978, who had earlier participated in a study of fluorosis in Perth (Western Australia), allowed 110 observers to look at their upper central incisors under good viewing conditions. Fluorosis in these teeth ranged from TF score 0 (no fluorosis) to TF score 3. The observers were university students, parents, public servants, or dentists. They responded to statement items about the appearance of the teeth. The results, based on just over 3000 responses, showed that lay and dental observers could distinguish between different fluorosis levels. In response to a statement that the teeth appeared pleasing, a large majority agreed when the TF score was 0, but agreement declined as the TF score increased; when the TF score was 3, most people disagreed. Similarly, observers felt that the appearance would increasingly embarrass the child as the TF score increased. Observers, except the dentists, tended to feel that higher TF scores indicated neglect on the part of the child.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360375 TI - Operatory ventilation and scavenger evacuation rate influence on ambient nitrous oxide levels. AB - Investigations have shown that greater than Federally-recommended levels of ambient nitrous oxide often exist in the dental workplace. The purposes of this investigation were to examine the influences of (1) operatory ventilation rate and (2) scavenger evacuation rate on ambient nitrous oxide concentrations within a closed dental operatory. This laboratory investigation utilized a scavenging nasal mask assembly (Porter/Brown) to deliver 40% nitrous oxide in oxygen, at a total flow rate of 5 L/min, to a mannequin positioned supinely in a dental chair. Eight experimental groups were assigned based on combinations of operatory air exchange rates (0, 5, 10, or 15 room air changes per hour) and scavenger evacuation rates (18.8 L/min and 21.4 L/min). Ambient nitrous oxide levels were monitored at four locations (0, 15.3, 30.7, and 61.4 cm) from the nasal mask by means of an infrared spectrophotometer (Miran 1B). The operatory air exchange rate was measured with a flow hood (Short Ridge) and manipulated to one of the desired ventilation rates. Time-weighted average (TWA) concentrations of ambient nitrous oxide (ppm) were continuously recorded at 15-second intervals with a microprocessor (DL332F Datalogger) connected directly to a microcomputer. The results demonstrated that significantly reduced (p < 0.05) ambient nitrous oxide levels were achieved with increasing room air exchange rates and the high scavenger evacuation rate. It was concluded that operatory ventilation and scavenger evacuation rates were significant control measures available for reduction of ambient nitrous oxide to Federally recommended levels. PMID- 8360376 TI - Influence of carbonate on sintering of apatites. AB - Sintering of carbonate apatite, prepared at 100 degrees C and pH 9.0 for 3 days, was studied by thermal analysis, x-ray diffraction, and infrared spectroscopy. The sintering temperature, at which the linear thermal shrinkage of isostatically compacted specimens increased sharply, decreased in proportion to the amount of carbonate initially present in the apatite. For example, specimens with over 8 wt% carbonate could be sintered at a temperature (650 degrees C) which was nearly 400 degrees C lower than that needed for sintering a specimen with no carbonate. Amounts of carbonate lost at the end of sintering, estimated chemically and by infra-red spectroscopy, were approximately equal to sample weight losses estimated thermogravimetrically. PMID- 8360377 TI - Crystallographic morphology of heterogeneous fluoridated carbonate apatites. AB - Carbonate-containing fluoridated apatites were synthesized with two different modes of fluoride incorporation: by supplying F-free solution initially, followed by a F-containing solution; and with the order of supply of these solutions reversed. Both of these heterogeneously synthesized fluoridated CO3 apatites showed typical apatitic x-ray diffraction patterns; and both had similar total fluoride contents (0.87 +/- 0.07 and 0.94 +/- 0.03 mmol/g, respectively), i.e., half of the maximum fluoride content of fluorapatite. However, they differed considerably in their crystallographic properties. The 300 reflection peaks of both apatites were split, and their patterns were slightly different. In the former, SEM observation revealed capsule-like crystals with a rounded hexagonal shape. However, the latter had many small crystals, similar to those of homogeneous CO3 apatite, adhering to the larger hexagonal crystals, which were also similar to homogeneous fluorCO3 apatite. Wavelength-dispersive spectroscopy attached to the SEM showed a higher fluoride intensity in the former spectrum than the latter. These results suggest that two different types of heterogeneous fluoridated CO3 apatites were formed, CO3 apatite covered with fluorCO3 apatite, and fluorCO3 apatite covered with CO3 apatite. The simple two-step supply system used in this study is helpful for the study of complicated heterogeneous formation of apatites. PMID- 8360378 TI - Analysis of the "shear" bond strength of pretreated aged composites used in some indirect bonding techniques. AB - Investigations of the repair of composites have shown that bond strengths can be significantly reduced at an interface involving an aged composite. Brackets placed by some indirect bonding techniques also have an interface involving an aged composite. This study investigated some of the properties of sealant composite interfaces and parameters affecting these properties independent of other regions and interfaces found in the total enamel-sealant-composite-bracket system using a shear bond-strength test and fractographic analysis. The effects of various pretreatments of 7-day-old composite surfaces on the bond strength and contact angle of a mixed sealant on these pretreated surfaces were determined. Fractured specimens with adhesive failure closest to the point of force application had low bond strengths (17.62 MPa), which could be correlated with surface pretreatment. Preliminary tests showed that acetone pretreatment produced the most consistently strong interfaces with the fewest adhesive failures of this type. Specimens with adhesive failure only in other regions had higher bond strengths (23.41 MPa), which showed no dependence on pretreatment. There was no statistical relationship between contact angle and bond strength. The data coupled with fracture path analysis suggest that: first, the critical region for fracture analysis is that part of the adhesive interface which is closest to the point of force application; second, failure during some dental shear bond strength tests probably occurs as a consequence of tensile stress induced by a bending moment rather than by shear stress; and third, specifying bond strength as breaking load/area may be incorrect. PMID- 8360379 TI - Acute toxicological effects of ingested tooth whiteners in female rats. AB - Tooth whiteners are considered as cosmetic agents to be used for bleaching teeth. Since tooth whitener may be swallowed during the whitening procedure, studies were conducted to determine whether ingestion of tooth whitener containing carbamide peroxide resulted in toxic effects. Adult female rats were used, and vaginal smears were examined daily to determine whether the animals were ovulating. Following an overnight fast, a single bolus of a commercial tooth whitener (5 g of tooth whitener/kg fasting body weight) was administered by gavage. Control rats received de-ionized water. After 2 h, mean respirations per min of animals receiving the tooth whitener Quik Start (contains 35% carbamide peroxide) decreased from 169 to 55, and body temperature decreased from 38.4 to 34 degrees C. Other distress signs included: labored breathing, loss of righting reflex, partial eye closure, bloody urine, and incontinence. Three of 22 animals (3/22) died within 48 h, of gastric hemorrhaging. Eight/10 rats stopped ovulating. At necropsy 2 weeks post-dosing, 10/19 animals had grossly bloated stomachs, and mucosal necrosis was observed histologically in 3. Animals receiving White & Brite or Nu-Smile (containing 10 or 15% carbamide peroxide, respectively) exhibited similar but milder symptoms. The data indicate that ingestion of large doses of commercial preparations of tooth whiteners may be acutely toxic, sometimes fatal, to female laboratory rats. PMID- 8360380 TI - The effect of fluoride application on fluoride release and the antibacterial action of glass ionomers. AB - The aim of this study was to investigate whether the release of fluoride and the antimicrobial effect of freshly mixed glass ionomers could be prolonged by application of fluoride on aged material. Test slabs of freshly mixed and aged (14 d in water) conventional and silver glass ionomer (Ketac-Fil and Ketac Silver, Espe, Seefeld, Germany) and composite (Silux Plus, 3M, St. Paul, MN) were fitted into the bottom of a test tube. A layer of S. mutans Ingbritt cells was centrifuged onto the test slabs, and the samples were incubated for 20 h in 1.7% sucrose solution. After the incubation, pH, F, and Ca contents of the fluid phase, and F, Mg, P, and K contents of the cells were determined. The aged glass ionomer samples were then covered with toothpaste (0.1% F) or with fluoride gel (1.25% F), and the composite samples with fluoride gel. After being thoroughly rinsed, S. mutans cells were incubated on the samples as above. The pH fall was significantly inhibited by freshly mixed glass ionomers, and there were changes in cellular cation and phosphorus contents. Large amounts of fluoride were found in the fluid and cells. For old glass ionomers, no inhibitory effect on pH fall could be seen. Fluoride release had decreased to a low level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360381 TI - The effect of the electrode potential on the release of mercury from dental amalgam. AB - The effect of the electrode potential on the rate of mercury dissolution from the matrix phase (gamma 1) of dental amalgam was investigated. Specimens of the Ag-Hg phase, with and without dissolved tin, were exposed to synthetic saliva and maintained at various potentials by means of a potentiostat. The amount of dissolved mercury was determined after 24 h by cold-vapor Atomic Absorption Spectrophotometry. Anodic polarization curves for the gamma 1 specimens and pure silver and mercury were also recorded. The results for the Ag-Hg phase showed a potential-independent dissolution rate between -0.6 and -0.1 V (SCE), followed by a sharp increase. Mercury dissolution from the Ag-Hg-Sn phase was much slower than from the tin-free gamma 1 phase, and potential-independent to +0.05 V (SCE); a sharp increase in mercury dissolution was observed at +0.1 V (SCE). The anodic polarization curves for the Ag-Hg-Sn phase indicated passivity between -0.67 V and +0.1 V (SCE), but no clear passivation for the Ag-Hg specimen, silver, or mercury. The results show that in the potential-independent region, mercury dissolved in the atomic form from both the tin-free and tin-containing gamma 1 phase. The increase in dissolution in the upper range of potentials was tentatively attributed to selective anodic dissolution of silver and an onset of electrochemical dissolution. The results indicate that the rate of mercury release from the gamma 1 phase of dental amalgam was not affected by potential changes due to alloying or galvanic contacts unless the potential exceeded some critical value. PMID- 8360382 TI - The level of mercury in human dental plaque and interaction in vitro between biofilms of Streptococcus mutans and dental amalgam. AB - Mercury levels (micrograms/mg dry weight) in dental plaque from amalgam and enamel surfaces in human subjects with amalgam restorations were (range, mean, SD) 0.5-1.31, 0.72, 0.34 and 0.01-0.54, 0.2, 0.19, respectively. The levels of mercury in plaque from amalgam surfaces were significantly higher than those from plaque on enamel (p < 0.001). No mercury was detected in plaque from subjects without amalgam restorations. The mean level of mercury in a 24-hour collection of plaque was 2 micrograms (median, 1.8 micrograms), an amount close to those calculated by other workers (1.2-1.7 micrograms) for the amount of mercury liberated in the mouth from amalgam restorations in 24 h. Freshly prepared amalgam liberated relatively large amounts of mercury into culture broth in the first 24 h of exposure; subsequently, the levels declined except in the presence of Streptococcus mutans. In vitro, biofilms of Streptococcus mutans facilitated the release of mercury from freshly prepared amalgam, in what appeared to be a cyclical fashion. Amalgam aged for two years did not release mercury, even when supporting the growth of an S. mutans biofilm. The resistance of aged amalgam was attributed to the presence of a passive tarnish layer. The mercury released by the biofilm had an effect on the composition of the biofilm. The biofilms on fresh amalgam had significantly lower levels of carbohydrate (p < 0.001-p < 0.01) and protein (p < 0.001-p < 0.02) than did biofilms on aged amalgam and on control stainless steel wires. PMID- 8360383 TI - A quantitative enzyme histochemical analysis of the distribution of alkaline phosphatase activity in the periodontal ligament of the rat incisor. AB - The spatial distribution of alkaline phosphatase (ALP) activity was examined in the periodontal ligament of the continuously growing rat incisor. With the indoxyl-tetrazolium salt method, enzyme activity was demonstrated in undecalcified cryosections, and the amount of reaction product was quantified. ALP activity appeared to be distributed heterogeneously. Its highest activity was found in the bone-related compartment of the ligament. In the tooth-related compartment and the supracrestal extension of the ligament, enzyme activity was significantly lower, but still higher than in the lamina propria of the gingiva. In the part of the ligament bordering the cementum, highest activity was found in the apical region just occlusal to Hertwig's epithelial root sheath, where formation of acellular cementum begins. From there toward the incisal edge, the activity of the enzyme gradually decreased. It is suggested that differences among the various parts of the periodontal ligament are related to local variations in phosphate metabolism and cementum deposition. PMID- 8360384 TI - Effect of centrifugal force on growth of mouse osteoblastic MC3T3-E1 cells in vitro. AB - The effect of biomechanical force on growth of skeletal tissue was studied in monolayer cultures of mouse osteoblastic MC3T3-E1 cells which were centrifuged at 320 g for 15 min to 72 h in a CO2 incubator. Centrifugation of the cells for 30 min in low concentrations (0.3 or 1%) of fetal bovine serum (FBS) caused a two fold increase of [3H]thymidine incorporation at 20 h from the start of centrifugation. However, centrifugation under 10% FBS caused no increase in [3H]thymidine incorporation into DNA. Under 0.3% FBS, [3H]thymidine incorporation increased in a manner dependent on the period of centrifugation and reached a maximum when the cells were centrifuged for 3 h. Stimulation of DNA synthesis by centrifugation was abolished in the presence of H-7, an inhibitor of protein kinase C. Moreover, conditioned medium collected from the centrifuged cultures increased [3H]thymidine incorporation by two-fold over the basal when added to a quiescent culture of MC3T3-E1 cells. These results suggest that centrifugal force stimulates growth of osteoblastic cells through autocrine secretion of some diffusible growth-promoting activity. On the other hand, centrifugation of the cells inhibited induction by FBS of alkaline phosphatase activity and calcium uptake, two indices of the differentiated phenotype of osteoblasts. PMID- 8360385 TI - Increased condylar growth after experimental relocation of the glenoid fossa. AB - Attempts to increase mandibular growth by the stimulation of condylar proliferative activity, either experimentally or with functional appliances in humans, have led to controversial results. The aim of this study was to measure changes in proliferative activity in the mandibular condyle after steady experimental posterior relocation of the glenoid fossa in the rabbit without actively interfering with normal masticatory action. The method differed from most previous experimental procedures, which force the mandible anteriorly to stimulate functional appliance therapy. Twelve 5-day-old rabbits underwent gluing of the interparietal, temporoparietal, and lambdoidal sutures. Three experimental and three control rabbits were injected with tritiated thymidine at 10, 15, 20, and 30 days and were killed after 2 h for histological and autoradiographic examination. The total number of labeled cells in the prechondroblastic layer was higher in the experimental group, the difference being greatest in the 20-day-old rabbits. The highest proliferative activity in the experimental group was found in the area immediately posterior to the articular contact surface. There was a tendency for the cartilage layers to be thicker in the experimental group, especially in the extreme anterior segments of the condyle. PMID- 8360386 TI - Steroid-resistant asthma. AB - The treatment of patients with asthma that is resistant to corticosteroids represents a therapeutic challenge, because corticosteroids are the most potent and potentially effective medications for severe asthma. Recent investigations have identified several functional defects in mononuclear cells and T lymphocytes isolated from patients with corticosteroid-resistant asthma, including abnormalities in proliferation, activation, and cytokine production. The development of medications with immunomodulatory effects on specific cellular functions represents an exciting step for more efficacious treatment for such patients. PMID- 8360387 TI - Bioequivalence of metered-dose inhaled medications. PMID- 8360388 TI - A prospective assessment of the remote practice of allergy: comparison of the diagnosis of allergic disease and the recommendations for allergen immunotherapy by board-certified allergists and a laboratory performing in vitro assays. PMID- 8360389 TI - The low prevalence of occupational asthma and antibody-dependent sensitization to diphenylmethane diisocyanate in a plant engineered for minimal exposure to diisocyanates. AB - BACKGROUND: Diisocyanate chemicals are leading causes of occupational asthma (OA). METHODS: We conducted a cross-sectional study of 243 workers exposed to diphenylmethane diisocyanate (MDI) in a urethane mold plant that had been designed to minimize MDI exposure (levels were maintained below 0.005 ppm and were continuously monitored). All participants were screened by questionnaire and tests for serum antibodies to MDI-human serum albumin (HSA). On the basis of questionnaire responses, diagnoses were derived that included OA; non-OA; work related and non-work-related rhinitis; and lower respiratory irritant responses. Serial peak expiratory flow rate studies were performed for 2 weeks in 43 workers with and in 23 workers without lower respiratory symptoms. RESULTS: Results of serial peak expiratory flow rate studies were abnormal in 3 (33%) of 9 workers with OA, in 2 (50%) of 4 with non-OA, and in 2 (9%) of 23 case control subjects. A significant association was found between peak flow rate variability and a questionnaire asthma diagnosis (chi 2 p < 0.002). Physicians confirmed three cases of OA, one of which occurred in a control worker who was free of symptoms. In all three cases asthma symptoms remitted after the worker left the workplace. Serum specific IgE and IgG levels were elevated in 2 of 243 workers, one of whom was prick test positive to MDI-HSA and had had cutaneous anaphylaxis after MDI exposure. CONCLUSIONS: On the basis of these cases, specific work activities associated with exposure to MDI were identified and corrective measures were instituted. Strict control and monitoring of ambient MDI exposure was associated with a low prevalence of specific sensitization to MDI and a lower than expected prevalence of OA. PMID- 8360390 TI - Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. AB - BACKGROUND: We recently demonstrated that T lymphocytes in bronchoalveolar lavage (BAL) fluid from atopic asthmatic patients were activated and expressed increased cytokine messenger ribonucleic acid (mRNA) for "TH2-type" cytokines, particularly IL-4 and IL-5, when compared with those in normal control subjects. This pattern of cytokines may determine the nature of the cellular infiltrate in the bronchial mucosa in asthma and hence the bronchial hyperresponsive (BHR) and symptoms that characterize this condition. METHODS: To examine the association between these cytokines and clinical measures of asthma severity we have extended our studies of BAL cells from subjects with atopic asthma. Numbers of BAL cells with positive in situ hybridization signals for IL-2, IL-3, IL-4, IL-5, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon-gamma were counted on cytocentrifuge preparations. Results were compared between patients with symptomatic (n = 19) and asymptomatic asthma (n = 10), and associations were sought with airway methacholine responsiveness, resting airway caliber, and asthma symptom scores. RESULTS: There were increased proportions of cells positive for IL-3 (p < 0.05), IL-4 (p < 0.005), IL-5 (p < 0.005), and GM-CSF (p < 0.005) mRNA in BAL fluid from patients with symptomatic asthma when compared with that from subjects free of symptoms, but no difference between the groups in numbers of cells expressing IL-2 and interferon-gamma mRNA. There were significant associations among numbers of cells expressing mRNA for IL-4, IL-5, and GM-CSF, and airflow restriction, BHR, and Aas asthma score. CONCLUSIONS: These findings support the hypothesis that cytokines contribute to airway events that determine asthma symptoms and BHR. PMID- 8360391 TI - Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum. AB - It is well known that helminthic infection can cause a polyclonal stimulation of the synthesis of IgE, which is dependent on interleukin-4 (IL-4) production, and it has been suggested that this can modulate the expression of allergic reactivity in tropical populations. We evaluated the effect of regular anthelmintic treatment, for a period of 22 months, on certain aspects of the allergic reactivity of children in a slum area of Caracas, Venezuela, where helminths are endemic. The treatment (Oxantel-Pyrantel; Quantrel) effectively eliminated intestinal helminthic infection and resulted in a significant decrease in the initially elevated total serum IgE levels. IL-4 was detectable in the serum, and a significant reduction in IL-4 was also observed after treatment. In contrast, both the immediate-hypersensitivity skin-test reactivity and serum levels of specific IgE antibody against environmental allergens were markedly increased in the treated children. In a group of children who were also evaluated in the same slum, but who declined treatment, a substantial increase in helminthic infection occurred, which was related to an acute deterioration of the socioeconomic conditions of Venezuela over the course of our study period. This was paralleled by a considerable increase in total IgE levels in these children and a decrease in the skin-test reactivities and specific IgE levels. The application of Prausnitz-Kustner passive transfer tests and analysis of specific IgE antibody levels indicated that the polyclonal stimulation of IgE synthesis by helminthic parasites results in mast cell Fc epsilon receptor saturation and suppression of specific IgE antibody synthesis. This inhibition of allergic reactivity is reversible by anthelmintic treatment. PMID- 8360392 TI - Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes. AB - BACKGROUND: T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes. METHODS: Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine. RESULTS: Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4. CONCLUSION: These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma. PMID- 8360393 TI - Airway allergy to trimellitic anhydride in guinea pigs: different time courses of IgG1 titer and airway responses to allergen challenge. AB - BACKGROUND: Trimellitic anhydride (TMA) is a low molecular weight chemical that may cause occupational asthma in human beings. The objectives of this study were to determine the time course of immune and airway responses to TMA in guinea pigs and to relate the immunologic response to the immediate responses in lung resistance (RL) and plasma exudation induced by allergen challenge. METHODS: We studied the effects of time course after sensitization on airway response to TMA in guinea pigs actively sensitized to free TMA, given by intradermal injection (0.1 ml of 0.3% TMA in corn oil). During weeks 1, 2, 3, 5, and 8 after sensitization, anesthetized animals were challenged with TMA conjugated to guinea pig serum albumin (TMA-GPSA), instilled via the airway route. Nonsensitized animals were challenged with the same amount of conjugate 4 weeks after intradermal injection of corn oil only. In the same animal, we measured both RL to monitor airflow obstruction and extravasation of Evans blue dye (20 mg/kg) to quantify airway plasma exudation. RESULTS: Instillation of TMA-GPSA (0.5%; 50 microliters) into the tracheal lumen caused a significant increase in RL, reaching a maximum at 2.5 minutes after the instillation in the 1-week group (9.0 +/- 5.9 cm H2O/ml/sec) and between 5 and 6 minutes in the 2-, 3-, 5-, and 8-week groups (9.4 +/- 4.8, 12.7 +/- 5.5, 3.7 +/- 1.1, and 1.7 +/- 0.2 cm H2O/ml/sec, respectively). The maximal increase in RL after the challenge in nonsensitized animals was 0.39 +/- 0.05 cm H2O/ml/sec. TMA-GPSA also produced significant extravasation of Evans blue dye at all airway levels in the sensitized groups, and the amount of dye in the peripheral airways was significantly greater than that in the trachea. Furthermore, the level of Evans blue dye in airway tissue increased with the time after sensitization, up to the latest time point tested (8 weeks). Specific IgG1 antibodies to TMA-GPSA demonstrated by ELISA were detected in all animals in the 3-, 5-, and 8-week groups, with maximal levels 5 weeks after sensitization. Specific IgG1 titers to TMA-GPSA significantly correlated with the level of Evans blue dye induced by challenge with TMA-GPSA but not with the increase in RL. CONCLUSIONS: Intradermal sensitization to free TMA induces specific airway allergy for a long period after sensitization. Specific IgG1 antibodies to allergen may influence allergen-induced plasma exudation rather than the airflow obstruction in this animal model of TMA-induced asthma. PMID- 8360395 TI - Pulmonary eosinophils express HLA-DR in chronic eosinophilic pneumonia. AB - BACKGROUND: Chronic eosinophilic pneumonia is a rare idiopathic disorder. role the eosinophil plays in the pathogenesis of this disease is unknown. The recent finding that nature eosinophils can express the class II major histocompatibility complex molecule HLA-DR suggests an immunologic role, perhaps through antigen presentation. The purpose of this research was to determine whether lung-derived eosinophils exhibit in vivo expression of HLA-DR. METHODS: Eosinophils were obtained simultaneously from bronchoalveolar lavage and peripheral blood from a 59-year-old woman with asthma and chronic eosinophilic pneumonia. Eosinophil enriched aliquots of peripheral blood were cocultured with human lung fibroblasts (with or without additional granulocyte-macrophage colony-stimulating factor). The percentage of cells expressing HLA-DR was quantitated by flow cytometric analysis. RESULTS: Eosinophils derived from bronchoalveolar lavage displayed in vivo expression of HLA-DR (86%) in contrast to those from peripheral blood (7%), suggesting compartmentalization of eosinophil activation within the lung. Peripheral blood eosinophils retained the capacity for HLA-DR expression when coincubated with lung fibroblasts (83%) with augmentation by granulocyte macrophage colony-stimulating factor (93%). CONCLUSION: These data demonstrate that lung eosinophil HLA-DR expression occurs in vivo; it may contribute to the pathogenesis of inflammatory lung injury. PMID- 8360394 TI - A magnetic resonance imaging evaluation of histamine-mediated allergic response in the guinea pig nasopharynx. AB - BACKGROUND: Magnetic resonance imaging (MRI) is a powerful technique for visualizing tissues with a high water content. In this study we used MRI to evaluate the effect of antigen and mediators of allergic responses on the nasopharyngeal airway of guinea pigs. METHODS AND RESULTS: Longitudinal relaxation time-weighted transverse images of the nasopharyngeal airway revealed a clearly defined airway lumen and mucosa. Topical administration of ovalbumin (0.00006% to 0.06%) to the nasopharyngeal airway of sensitized guinea pigs caused a concentration-dependent reduction (34% +/- 1%, maximum) in airway luminal volume and a corresponding increase (28% +/- 3%, maximum) in the volume of the airway mucosa. These effects were duplicated by histamine (10(-5) to 10(-3) mol/L), but not by methacholine (10(-3) mol/L). The antigen-induced changes in airway and mucosal volumes were dose-dependently inhibited by the H1-antagonist loratadine (0.3 to 3 mg/kg, administered orally). On the other hand, topical administration of a decongestant drug, oxymetazoline (250 micrograms per guinea pig), had no effect on the response to antigen. CONCLUSIONS: These results indicate that MRI is a useful technique to measure allergic responses in the airways and identify that histamine is an important mediator of the obstruction that occurs in the nasopharyngeal airway of guinea pigs after antigen challenge. PMID- 8360396 TI - Effect of a topical corticosteroid on airway hyperresponsiveness and eosinophilic inflammation induced by trimellitic anhydride exposure in sensitized guinea pigs. AB - BACKGROUND: Topical corticosteroids are effective in the treatment of asthma by improving bronchial hyperresponsiveness and reducing airway inflammation. METHODS: We assessed the effect of a nebulized corticosteroid, budesonide, on airway hyperresponsiveness and inflammatory response provoked by inhalation of trimellitic anhydride (TMA) dust, a known cause of occupational asthma in human beings, in guinea pigs sensitized to the free hapten. Male Dunkin-Hartley guinea pigs (n = 24) were injected intradermally with 0.1 ml of 0.3% TMA in corn oil, followed by exposure 21 to 28 days later to five consecutive doses of budesonide aerosol (0.5 mg/ml) or saline solution, administered for 10 minutes every 12 hours. They were then exposed (noses only) to TMA dust (8 mg/m3) or air for 1 hour (four groups, n = 6 in each). Airway responsiveness to acetylcholine, defined as the concentration needed to cause a 200% increase in lung resistance (PC200), was measured 8 hours later. RESULTS: In saline-treated guinea pigs exposed to TMA, mean PC200 was 0.094 mmol/L (geometric SEM, 1.4 mmol/L) compared with 0.31 mmol/L (geometric SEM, 1.3 mmol/L, p < 0.05) in those guinea pigs pretreated with budesonide. In sham-exposed sensitized guinea pigs, PC200 was 0.35 mmol/L (geometric SEM, 1.2 mmol/L), which was not significantly different from the budesonide-treated group (0.36 mmol/L; geometric SEM, 1.3 mmol/L). There was a significant increase in the number of eosinophils in the subepithelium of guinea pigs further exposed to TMA dust (71.5 +/- 6.8 cells/unit area [mean +/- SEM]) compared with those exposed to air (22.7 +/- 6.7, p < 0.01). Budesonide did not inhibit the number of subepithelial eosinophils of guinea pigs exposed to TMA dust (54.0 +/- 3.7 cells/unit area) or in those exposed to air (24.3 +/- 6.7 cells/unit area) and did not affect the increase in eosinophils found in bronchoalveolar fluid. CONCLUSIONS: Budesonide significantly inhibited the increase in airway responsiveness but not the eosinophilic inflammation induced by exposure to TMA dust in sensitized guinea pigs. PMID- 8360397 TI - Estimation of nasal epithelial lining fluid using urea as a marker. AB - BACKGROUND: The luminal surface of respiratory mucous membranes is lined with an epithelial lining fluid (ELF) layer. Previous attempts to determine ELF volumes in airways have used dyes or freely diffusible molecules such as urea, yet have not led to a universally accepted method. The nasal mucous membrane provides an accessible area to examine whether urea is an appropriate marker of respiratory ELF volume. METHODS AND RESULTS: Collection of undiluted nasal secretions after either glandular stimulation or induction of vascular permeability confirmed that plasma urea and nasal urea concentrations are equivalent. Baseline ELF volume was calculated as 800 microliters/nostril. The calculated molar concentrations of urea in ELF did not vary with either methacholine or histamine challenge. CONCLUSIONS: These data indicate the plasma, interstitial, glandular, and ELF urea concentrations are equivalent and, therefore, that urea is a useful marker of ELF volume in the nasal mucosa. PMID- 8360398 TI - Immunologic studies of the mechanisms of occupational asthma caused by western red cedar. AB - BACKGROUND: Occupational asthma caused by western red cedar (Thuja plicata) is a common problem in sawmill industries. The objective of this study was to examine the cellular and immunologic mechanisms of western red cedar asthma (WRCA) more closely. METHODS: Bronchial biopsy specimens, bronchoalveolar lavage (BAL) mast cells and peripheral blood basophils from patients with WRCA, patients with atopic asthma, and nonatopic control subjects were challenged in vitro with plicatic acid (PA), PA-human serum albumin conjugate (PA-HSA), grass pollen, or calcium ionophore. RESULTS: PA (100 micrograms/ml) released histamine from the basophils of 9 of 11 patients with WRCA, 1 of 7 patients with atopic asthma, and 2 of 7 normal subjects. PA triggered histamine release from 10 of 11 bronchial biopsy specimens and 8 of 8 BAL samples from patients with WRCA. Interestingly, PA released histamine from BAL cells and bronchial biopsy specimens from 3 of 7 normal subjects but in none of the patients with atopic asthma. PA-HSA-induced histamine release from basophils and biopsy specimens was confined to patients with WRCA. PA-specific IgE was not detectable in serum from most patients with WRCA, and their serum did not transfer PA sensitivity to human lung fragments or lactate-stripped basophils. After pretreatment with anti-IgE in the absence of calcium, basophils from 14 subjects with WRCA still responded to PA (mean 64% to 67% of pretreatment response), whereas responses to grass pollen or anti-IgE were abolished. CONCLUSIONS: This study confirms that PA releases histamine from bronchial mast cells of most patients with WRCA but not from those of patients with atopic asthma. The PA response of some normal subjects suggests that PA may have both specific and nonspecific actions on mast cells and basophils, whereas the serologic studies indicate histamine release in WRCA cannot simply be attributed to PA-specific IgE. PMID- 8360399 TI - Duration and magnitude of action of 50 and 100 micrograms of inhaled salmeterol in protecting against bronchoconstriction induced by hyperventilation of dry cold air in subjects with asthma. PMID- 8360400 TI - Papain-induced allergic rhinoconjunctivitis in a cosmetologist. PMID- 8360401 TI - Eosinophilia in early-stage human immunodeficiency virus infection. PMID- 8360402 TI - Correction regarding an adverse reaction to the recombinant hepatitis B vaccine. PMID- 8360403 TI - Putting osteoporosis in perspective. AB - Osteoporosis is characterized by a reduction in bone mineral density (BMD). Dietary patterns that encourage adequate calcium intake are essential to maximal development and later maintenance of bone mass. The majority of white women are at risk for osteoporosis-related fractures, especially in the wrist, spine, and hip. The degree of fracture risk at a specific bone site is best assessed by measuring BMD with single- or x-ray-photon absorptiometry. BMD in adults of any age is quite variable. Numerous diet and lifestyle factors influence BMD and, in turn, fracture risk. Sufficient evidence exists for a relationship between BMD and diet, particularly calcium and vitamin D; amenorrhea; body weight; alcoholism; smoking; and physical inactivity. Less convincing evidence exists for a relationship with dietary protein, dietary phosphorus, and caffeine intake. To minimize fracture risk, young women should have regular menses, consume a nutritionally adequate diet (according to the principles of the Food Guide Pyramid), perform regular physical activity, only consume a moderate intake of alcohol (if any), and not smoke. Postmenopausal women should follow those same guidelines and should seriously consider estrogen replacement therapy. Elderly persons especially should ensure adequate calcium and vitamin D nutriture. Currently, osteoporosis is the rule, rather than the exception, in old age for many white women. Dietitians can help reduce the prevalence of this disorder. PMID- 8360404 TI - The role of weight management in the health of women. AB - Weight management plays a central role in preventing many diseases that affect women. Lifelong hormonal, psychological, and environmental influences on women elicit a set of behavioral and biological responses distinctive from men that place them at increased risk for overall weight concerns, weight gain, and obesity. Limitations of current treatment call for increased research to improve our understanding and guide efforts in this important aspect of women's health. Research needs to be conducted to define realistic and obtainable weight goals and to design educational strategies to promote health and self-esteem. Research in the field of weight management should be directed to understanding gender differences, etiologies, and effective treatments. PMID- 8360405 TI - Women's health care: changing concepts. PMID- 8360406 TI - Identifying predictive variables for long-term weight change after participation in a weight loss program. AB - OBJECTIVE AND DESIGN: To determine if there was an association between weight change and 31 independent variables among obese persons 2 years after a weight loss program. Data were obtained from subjects' records and from questionnaires administered at enrollment and after a 2-year follow-up. SETTING: The 8-week weight control program was taught by registered dietitians and developed by the staff at the Sid Richardson Institute for Preventive Medicine, Houston, Tex. SUBJECTS/SAMPLES: Of the 1,460 subjects who attended at least one of eight classes, 509 subjects (123 men and 386 women) responded to the mailed follow-up questionnaire. MAIN OUTCOME MEASURES: Associations between weight change and the 31 independent variables were assessed. Heights and weights were measured by the dietitians during treatment. Two-year follow-up weights were self-reported. STATISTICAL ANALYSES PERFORMED: Analysis of variance was used for 16 of the independent variables. For the remaining variables we performed a test of the null hypothesis that the correlation coefficient was 0 based on the test of the regression coefficient between the independent and dependent variable. A stepwise regression process was used to determine the best combination of variables predictive of weight change. RESULTS: Of the 31 independent variables, 16 were significantly predictive of weight change. The adjusted R2 for the entire group of 16 variables was .379. Thus, 37.9% of the variance was explained by the joint efforts of the 16 variables. Eight variables with an adjusted R2 of .371 (accounting for 37.1% of the variance) were most important: feeling in control of eating habits, percentage over ideal body weight at enrollment, percentage of weight lost during the 8-week treatment, frequency of weight measurement, increase in physical activity, frequency of eating in response to emotions, number of pounds gained before subject resumed diet, and occupation. APPLICATION/CONCLUSION: The predictive variables for weight change may be useful to professionals who treat obese clients and may improve success rates of long term weight loss. PMID- 8360407 TI - Metabolic and anthropometric changes in female weight cyclers and controls over a 1-year period. AB - OBJECTIVE: Women who diet to lose weight often regain the weight over time, and the cycle repeats itself. The objective of this study was to identify a group of female weight cyclers and to match them with a control group who had never consciously tried to lose weight. For 1 year, weight patterns, eating habits, metabolic parameters, and body composition were assessed to determine whether there was a relationship between weight cycling and these variables. DESIGN: Measurements were done at baseline and at 6 and 12 months. Changes in weight, diet, and exercise were monitored throughout the year. SETTING: All testing was done at a university physiology laboratory. SUBJECTS/SAMPLES: Nine weight cyclers with a notable history of dieting and food restriction were recruited. Subsequently, nine control subjects were selected and matched for age, height, weight, lean body mass, and exercise habits. MAIN OUTCOME MEASURE: The observational study included measures of 3-day diet records, skinfold and girth, serum glucose, insulin and triiodothyronine, and resting energy expenditure. STATISTICAL ANALYSES PERFORMED: The main variables were analyzed using a 2 x 3 (diet group x time) analysis of variance with repeated measures on the time factor. Comparison of the means was done by Tukey post hoc test. RESULTS: A 7 point satisfaction scale indicated that the weight cyclers were dissatisfied with their weight compared with the noncyclers (P = .03). Otherwise, there were no differences between groups in dietary intakes or the physiologic variables. APPLICATIONS/CONCLUSIONS: In the parameters measured, a history of weight cycling did not affect the metabolic profiles of the weight cyclers compared with the noncyclers. PMID- 8360408 TI - Resting energy expenditure in the obese: a cross-validation and comparison of prediction equations. AB - OBJECTIVE: To examine the accuracy and precision of 12 equations or tables for predicting resting metabolic rate (RMR) in obese persons. DESIGN: Observational (correlational) study. SETTING: Obesity Research Center, St Luke's/Roosevelt Hospital, New York, NY. SUBJECTS/SAMPLES: One hundred twenty-six (73 women, 53 men) healthy, obese subjects recruited through the Obesity Research Center's Weight Control Unit. MEASURES: RMR by indirect calorimetry. Weight and height were measured to the nearest 0.1 kg and to the nearest 1 cm. STATISTICAL ANALYSES PERFORMED: Bivariate regression of predicted RMR on measured RMR; paired t tests for the difference between means of predicted RMR and measured RMR. RESULTS: Of the 12 prediction equations, 6 had intercepts or slopes that were significantly different from 0 and 1, respectively. With two exceptions, the equations accounted for between 56% and 63% of the variance in measured RMR. The Robertson and Reid (1952) equation and the Fleisch (1951) equation performed best with our obese sample. APPLICATIONS/CONCLUSIONS: The Robertson and Reid (1952) and the Fleisch (1951) equations are recommended for clinical use with obese patients. PMID- 8360409 TI - Predictors of body satisfaction in college women. PMID- 8360410 TI - Eating disorders: the changing role of nutrition intervention with anorexic and bulimic patients during psychiatric hospitalization. PMID- 8360411 TI - Assessment of differences between compliers and noncompliers in outpatient research diet studies. PMID- 8360413 TI - Cancer patients need referrals to dietitians. PMID- 8360412 TI - Health care reform--where ADA stands. AB - Few issues have galvanized the American public as dramatically as health care reform. Virtually everyone agrees that health care costs, quality, and accessibility require close examination and a prescription for change. Not everyone, however, agrees on the exact nature of this change. It is extremely important that we awaken the public and our policy makers to the vital role nutrition plays in the health care system. ADA is dedicated to this effort. Stay tuned as the health care reform plan unfolds. This effort is likely to be long term and will require your commitment, dedication, and energy to make nutrition services in health care reform a reality. PMID- 8360414 TI - Body temperature in persons with anorexia nervosa. PMID- 8360415 TI - Forces for research. PMID- 8360416 TI - ADA's nutrition & health campaign for women. PMID- 8360418 TI - The American Dietetic Association 76th Annual Meeting and Exhibition. Anaheim, California, October 25-28, 1993. Abstracts. PMID- 8360417 TI - Role of nutrition in the prevention and treatment of coronary heart disease in women. AB - Coronary heart disease (CHD) is the major cause of death in women. Because the manifestation of CHD differs in women and men (men are more likely to have acute CHD and women are more likely to have chronic CHD), it is imperative to explore the unique aspects of CHD in women. In addition, there is a critical need to increase our understanding of the effect of CHD risk factor modification on coronary morbidity and mortality in women. Several major CHD risk factors in women, such as elevated blood lipids and lipoproteins, body weight, and, frequently, hypertension, are beneficially responsive to nutrition intervention. Approximately 27% of all women and 50% of women aged 55 to 74 years are candidates for dietary intervention. The fact that women respond positively to dietary intervention has been well established by researchers. Studies are needed to determine the efficacy of risk factor modification achieved by dietary and other hygienic approaches as well as by other more rigorous therapies (eg, drugs and surgery) on the primary and secondary prevention of CHD in women. Finally, it will be important to understand the effects of gender, menopausal status, and age on dietary responsiveness. We must gain a better understanding of these issues so that we may significantly reduce the incidence of CHD in women. PMID- 8360419 TI - [Diurnal vision and mesopic vision in patients with monofocal and diffractive bifocal implants. A prospective and comparative study]. AB - In a prospective study we implanted 34 monofocal posterior chamber lenses and 34 diffractive bifocal posterior chamber lenses. The corrected distance acuity of both groups with comparable age showed no significant difference. To compare functional results of both groups under mesopic conditions we examined all patients with the Mesoptometer II. We determined the visual acuity under field luminance of 1.0 cd/m2 and contrast thresholds under field luminance of 0.1 cd/m2. The results-of patients with diffractive bifocal posterior chamber lenses were significantly reduced compared with patients with monofocal posterior chamber lenses. PMID- 8360420 TI - [Epidemiological data on primary open-angle glaucoma and treatment in the department of Marne]. AB - A descriptive cross-sectional epidemiological survey of primary open-angle glaucoma (POAG) was carried out in the department of Marne, France, between October 1990 and May 1991. The aim of the study was to obtain socio-medico demographic data on glaucoma patients who were treated for a period of one year or more. Fifty per cent of the ophthalmologists in the department of Marne participated in the study by having their patients complete an anonymous questionnaire at home. Eighty-five per cent of the 407 patients replied. This response rate to the investigation did not vary significantly (p > 0.90) with respect to the ophthalmologist. However, forgetting to distribute the questionnaires to the patients was variable from one physician to the other. The prevalence of POAG cases undergoing treatment was between 0.15 and 0.36% for the whole population; between 0.37 and 0.89% for patients over the age of 40 years; 0.67 and 1.67% after the age of 60. The same number of women and men are affected, but the risk is 1.33 times greater for men after the age of 60. The geographical distribution of the patients is identical to that of the general population. Sixty-two per cent of the patients take other drugs as well and this proportion increases with age (p < 0.0001); 24% of the subjects have hypertension and 10.6% are diabetic. Half of the patients have received anti-glaucoma therapy for 6 years or less; 94% take beta-blockers, 18% take miotics and 12% use adrenergic drugs. More women instil their eyedrops on their own (79% vs 57%; p < 0.0001). Ten per cent of patients have had glaucoma operations and this proportion increases with age (p < 0.03). The frequency of laser treatment is 20%. Glaucoma patients seem to be faithful to their ophthalmologist as 65% of them go to the same one for follow-up. Our study shows that this type of investigation is well received by the patients. PMID- 8360421 TI - [Therapeutic observance and life of patients with primary open-angle glaucoma. Apropos of 341 cases in the department of Marne]. AB - Patient compliance with treatment is an important factor in chronic diseases such as primary open-angle glaucoma (POAG). Among the 404 glaucoma patients included in our study in the department of Marne (France), 341 patients responded by completing an anonymous questionnaire at home in which the psychological effect of the illness, their knowledge about it, compliance with treatment and their relationships with the physician were explored. Sixty-eight per cent of these patients confirmed strict compliance with the treatment prescribed; this rate does not vary with respect to either the ophthalmologist (p = 0.57), or the duration of treatment (p = 0.42). Half of the remaining patients only alter the hours of their treatment and 6% forget to instill the eyedrops on certain days. According to our survey, the principal causes of poor compliance are forgetfulness, time constraints with other duties, poor doctor-patient relationship and lack of sufficient knowledge about the disease and its treatment. The majority of patients (59%) are minimally disturbed by the treatment; 2/3 of the subjects do not feel any change in their moral whereas 15% are more depressed or weakened since the time the illness was discovered. Fifty six per cent of them observed little or no change in their vision; 32% believe to have a moderate or considerable repercussion and 6% claim a very severe visual deterioration. Generally, patients appear to have a positive attitude towards their illness and do not try to deny it. Thirty-eight per cent of them consider it as a handicap which they can overcome and 42% have either no particular opinion or take it as a minor event. PMID- 8360422 TI - [HERETAIN: a computer-assisted diagnosis system for hereditary retinal syndromes]. AB - The diagnosis of hereditary retinal syndromes may be difficult for a physician because of their number and variability. A computer assisted diagnosis of these syndromes can be useful in such cases. We used an identification software (XPER) for this purpose. The data base contains more than 67,000 elementary data that enable us to define 115 hereditary retinal syndromes. The knowledge is not represented by description of typical cases or diagnostic procedure rules but by structured description of syndromes defined by the group of experts. This CAI software is characterised by specific optimising procedures, deductive algorithms and dissimilarities calculus and enables very fast diagnoses by limiting the number of complementary analyses and thus the cost of this research. This system is extensible and justifies all its conclusions, its user-friendly data representation makes it accessible for any physician even if he does not master computers. The selected pathology field seems very suitable to developing a computer assisted diagnosis system: many low frequency syndromes, meaningful precise diagnosis for genetic and professional counseling, therapeutic expectations due to progress in molecular genetics. According to the authors, HERETAIN is one of the largest computer assisted decision support systems in ophthalmology. PMID- 8360424 TI - [Current status of treatment of pterygium]. AB - After reviewing the various etio-pathogenic hypotheses for pterygium in which the discontinuity of the lacrymal film at the corneo-limbic junction appears to play an essential role, the authors discuss the current therapeutic choices. The value and place of lamellar keratoplasty overlapping the limbus are discussed. PMID- 8360423 TI - [Etiologies and risk factors of endophthalmitis]. AB - Endophthalmitis is a serious disease with multiple aetiologies. Its development seems to be dependent upon various risk factors. Among 99 cases of endophthalmitis, 79% were secondary to intraocular surgery especially cataract surgery and perforating ocular trauma. To identify risk factors of post-cataract surgery endophthalmitis, we performed a case-control study: 55 cases and 269 controls were used. Five risk factors were identified: duration of the operative procedure longer than 60 min, suture dehiscence, persistence of lens mass, traumatic cataract and left eye operated. The importance of prevention of endophthalmitis by avoiding such risk factors is raised. PMID- 8360425 TI - [Development of bilateral Kayser-Fleischer rings in a patient operated on by radial keratotomies]. PMID- 8360426 TI - [Combined operation of trabeculectomy, cataract extraction and implantation of an artificial lens in the posterior chamber]. PMID- 8360427 TI - [Elongation of the levator palpebrae superioris in palpebral retraction in Basedow's disease]. PMID- 8360428 TI - [Invasive carcinoma of the conjunctivo-corneal limbus. Apropos of a case]. AB - The limbus is an elective site of epithelial malignancies, mostly represented by precarcinomatous lesions. An 83-year-old female patient was operated for an exophytic tumor of the limbus. Histological examination showed an invasive squamous carcinoma. As the excision was not complete, complementary radiation therapy (45 Gy) was applied with a good short-term result. This case report emphasizes the value of early diagnosis and treatment of limbal tumors at the stage of precancerous lesions. PMID- 8360429 TI - [Treatment of recurrent erosion of the cornea]. PMID- 8360430 TI - [Abortions of immunologic origin. A trial of etiologic classifications and therapeutic consequences]. AB - Repeated unintentional abortions are an agonizing problems for many couples. When the cause is unexplained an immunological reason is often invoked. There have been many theories, but none have been able to be proven. Progress in immunology makes it possible to predict that these mechanisms will become better understood. At the present time the most recent work presented by the authors underlines the fact that there are probably several different immunological mechanisms causing abortion. When the mechanisms can be identified using current techniques, it may be possible to suggest the treatment suited to each one of these situations and to abandon empirical treatment as is at present used in these repeated abortions. PMID- 8360431 TI - [Local and long-term systemic risks of silicone breast implants]. AB - A woman of 59 years of age, who had bilateral breast implants, 20 years earlier, presented with both breasts hard, inflamed and ulcerated, which suggested bilateral siliconomas. Bilateral mastectomy was carried out in two stages because she developed disseminated intravascular coagulation during the first operation. PMID- 8360432 TI - [The unexpected occurrence of spontaneous pregnancy during hormone replacement therapy for premature menopause]. AB - Ovarian failure may be an irreversible consequence of cancer treatment for premenopausal woman. The diagnosis must be do of repeated gonadotropins and estrogen levels. A case of pregnancy is reported in a 26-year-old woman with iatrogenic menopause since eleven years and receiving estrogen/progesterone replacement therapy. The patient's age at the time of therapy, the amount of radiation that the ovaries received and the dose of the antineoplastic agent(s) are the critical factors for determine future ovarian functioning. PMID- 8360433 TI - [Active forces of urinary continence and urethral fatigability. Application to stress urinary incontinence in women]. AB - Eighteen women who had urinary stress incontinence were studied to find the existence of urethral fatigue on effort by using a sphincterometric technique. Urethral pressure measurements at rest as compared with after six heavy coughs showed a mean lowering of the urethral pressure of 40% (range 24.5%-90%) in 10 women. Spectral analysis of the electromyographic trace of the striated urethral sphincter at rest and then after coughing confirms that the striated muscle and the periurethral tissues are involved with a marked quantitative lessening of electric sphincter activity. The clinical, physiopathological, prognostic and therapeutic consequences of this new concept are discussed, together with their relationship to other active forces involved in continence. PMID- 8360434 TI - [Robert's uterus with menstrual retention in the blind cavity]. AB - Robert's uterus or asymmetric septate uterus is a rare malformation. It presents with two cavities, one of which is blind. The authors report an original case: the blind cavity, on the right side of the septum, contained retained secretions. The embryologic and physiopathologic mechanism of this anomaly still are to be discussed. PMID- 8360435 TI - [Intraperitoneal chemo-hyperthermia in the treatment of peritoneal carcinomatosis of ovarian origin. Initial cases, physiopathologic data]. AB - The authors report the first results using intraperitoneal hyperthermic chemotherapy with mitomycin C or cisplatinum with protective hypothermia up to 32 degrees C in four cases of peritoneal carcinomatosis secondary to cancer of the ovary which was resistant to conventional treatment. They were stage III and IV in the FIGO classification. There were no post-operative complications. Two patients are still alive 4 and 6 months after intraperitoneal hyper-chemotherapy. Hypothermia has its own action of destroying tumour cells and potentiates the effects of chemotherapy. We have, following the work of the japanese, devised a therapeutic regime combining chemotherapy and intraperitoneal hyperthermia. PMID- 8360436 TI - [The association of dermatopolymyositis and cancer of the ovary]. AB - Different aspects of the relationship between dermatopolymyositis and cancer of the ovary are emphasised here. A clinical case support these aspects. In the incidence of cancer of the ovary it is remarkable that there is often a relationship between the two conditions. Usually the diagnosis of the dermatopolymyositis comes before the cancer is discovered. This means that decisions have to be taken as to how far investigations for the cancer should be carried out when dermatopolymyositis has been diagnosed. PMID- 8360437 TI - [Pheochromocytoma of the broad ligament]. AB - The authors report a rare case where a pheochromocytoma which was not in the adrenal gland occurred in the broad ligament. A review of the literature resulted in only three published cases being found. When the symptomatology suggests that there may be a pheochromocytoma in the body one has to research where it is sited and one has to think of such a possibility if a tumour in the broad ligament is found during an operation, so that the risks of operating on these tumours can be lessened. PMID- 8360438 TI - [To be born or not to be. Epidemiologic, judicial and psychological aspects]. AB - The requisites for filling up birth certificates in France (> or = 180 days of pregnancy and vitality at the registration of birth) are different from the criteria recommended by the World Health Organisation (WHO) (at least 500 g) for national statistics. The number of stillborn babies and neonatal deaths known from two different sources in the Nord-Pas de Calais Region in 1988-1989 have been compared ie: the vital statistics published by INSEE and the data of a survey carried out in hospitals according to the WHO criteria. Among the 808 known perinatal deaths in the survey, 305 (37.7%) were ignored or were not classified in the same categories by the registration services for vital statistics. 230 children including 29 born alive had not been registered and 75 children born alive had been registered as still born. The disparity in these definitions between INSEE and the WHO has serious consequences: the perinatal mortality measured by INSEE is underestimated by 28%, in comparison with mortality registered according to the WHO criteria. The 180 day threshold of viability reduces the social rights of employed women and makes it more difficult for them to have the money they spent on medical care refunded. Finally, as it is impossible to find a trace of these children who were not legally registered since they were under the threshold of viability, the mourning response of parents to perinatal deaths is all the more difficult. Current evolution in the threshold of viability observed in maternity units, makes it necessary to change the criteria which are applied for the legal registration of births. PMID- 8360439 TI - [Anti-Tja (PP1Pk) isoimmunization. A case, a review of the literature]. AB - AIM: A review of the literature concerning the very rare anti-PP1Pk isoimmunisation with a personal case. CLINICAL MATERIAL: Anti-PP1k antibody gives rise to the high risk of abortion in the first and the second trimester (in a different series the risk is 50-70%). A 19-year-old patient who had this antibody was helped by a plasmaphoresis repeatedly between the 6th and the 25th week of pregnancy. Cordocentesis was carried out to estimate fetal haemoglobin from the 25th week onwards. A set caesarean section was carried out at 36 weeks because of intrauterine growth retardation and the development of fetal anaemia. DISCUSSION: The authors suggest research based on the known immunohaematological factors concerned with this isoimmunisation and on the main treatments available (plasmaphoresis, cordocentesis, and delivery at a set time). CONCLUSION: Until now there have been very few cases and only four similar cases to ours have been reported in the literature. That is why it is so difficult to suggest a well defined strategy for treating these patients. PMID- 8360440 TI - [The use of sulprostone (Nalador) in the evacuation of uterine contents. Apropos of 32 cases at the Department of Gynecology, University Hospital Center, Nimes, over 2 years (a retrospective study)]. AB - We have studied the use of sulprostone in evacuating uterine contents in 32 patients, the majority of whom were in the second trimester of their pregnancies. There are three ways to administer the drug (continuous intravenous, intermittent intravenous, and intramuscular); the best results were obtained when the drug was administered continuously intravenously. It was well tolerated, the use of Nalbuphine reducing pain. There were few side effects. The use of this product is discussed in connection with a few of the cases as well as the possible alternative treatments in difficult cases. PMID- 8360442 TI - [Swallowing of an amniotic string by a fetus at term]. AB - Amniotic band syndrome is a rare pathology which involves a group of fetal malformations due to the formation of bands between the fetus and the extraembryonic derivatives. These fetal malformations are extremely variable and their type depends upon the period of gestation during which the bands develop. In rare cases, these bands could strangulate the umbilical cord vessel and lead to fetal death. The authors report an exceptional case fo swallowing of the amniotic band by a fetus at term and fetal death due to strangulation of the umbilical cord vessels by amniotic band. PMID- 8360441 TI - [Gestational age and fetal lung maturity]. AB - In order to assess the lung maturity of the fetus, a biochemical analysis using two reliable, simple and rapid methods (FLM-TDX Abbott and determination of phosphatidylglycerol (PG) have been carried out on 166 amniotic fluids taken by amniocentesis. The patients were particularly pregnant women presenting disorders such as diabetes (n = 41), premature rupture of the membranes (n = 30), hypertension (n = 20), intra uterine growth retardation (n = 13) and gemellar pregnancies (n = 27). The lung maturity of the fetus has been considered as mature (no risk of any hyaline membrane disease: HMD) when the phospholipid rate is higher than 50 mg/g albumin (FLM-TDX Abbott), associated or not with the presence of PG (PG positive). The latter phospholipid was present only in women whose pregnancy was about 35 weeks. Besides, our results show a very large disparity of the phospholipid rates (FLM-TDX) in the amniotic samples for an identical gestational age. Values from 9 to 124 for pregnancies with term of 31 weeks, and from 21 to higher than 160 for those of 38 weeks. In infants born not later than 48 hours after the amniotic punction (n = 30), four of them presented an HMD. The FLM-TDX values were less than 30 for three cases and equal to 52 for the fourth. The term of these newborns was 37 weeks or more for three of them, and 31 weeks for the last one. Our study confirm that the TDX-FLM Abbott is useful to assess the fetal lung maturity and does not correlate with the gestational age. PMID- 8360443 TI - [Term birth of a twin after the rupture of the uterine horn at 15 weeks gestational age]. AB - Having treated a case which resulted in the delivery at term of an intrauterine twin when the other twin had been lost after the rupture of a uterine cornu which itself followed a salpingectomy without removal of the interstitial portion of the tube brings the authors to discuss the physiopathology and the symptomatology of such cases. They also discuss the value of resecting the interstitial portion of the tube and what management should be when there is a live intrauterine pregnancy. PMID- 8360444 TI - [Cloacal dysgenesis and vaginal delivery]. AB - The failure of urorectal septum to form and divide the cloaca into rectum dorsally, and urogenital sinus ventrally, results in a cloacal dysgenesis. It is an extremely rare anatomic malformation of the genito-urinary tract and alimentary tract. A case of pregnancy and vaginal delivery in a patient with cloacal dysgenesis type II and previous heart operation is presented. Both mother and newborn were in good condition. The way of treatment of such patients is discussed. PMID- 8360446 TI - [Infectious endocarditis of gyneco-obstetric origin. Apropos of 15 cases]. AB - With the object of analyzing current characteristics of post-partum and post abortum infective endocarditis (IE), authors carried out a retrospective study of 15 cases between september 1985 and may 1992. Mean age was 22.2 +/- 4.0 years. Origin of sepsis was delivery (1 case), abortion (14 cases). There was no underlying cardiac lesion in 9 cases, rheumatic heart disease in 6 cases. Infecting organisms were Staphylococcus aureus (n = 6), streptococcus D (n = 3), Clostridium perfringens (n = 2). There were 10 acute and 5 subacute IE, 7 right sided, 7 left-sided, and 1 right and left-sided IE. Vegetations were determined by transthoracic echocardiography in 12 cases (80%). The main complications were heart failure (15 cases), and pulmonary or arterial embolism (7 cases). Lethality was 53.3% and was not different in tricuspid acute IE and left-sided IE. Treatment was the more difficult as cardiac surgery is expensive or even inaccessible. Accordingly, prevention is primordial. It consist of antibiotic prophylaxis and fight against illicit abortion. PMID- 8360445 TI - [Complete and complicated tears of the perineum in spite of preventive incision. A study of the risk factors and the short-term consequences]. AB - A retrospective study of case controls was carried out by postal enquiry to find out the risk factors for complete complicated tears (DCC) of the perineum occurring after prophylactic episiotomy. There were 33 such cases of DCC out of 8,039 vaginal deliveries which means 0.41% in the University Centre in Grenoble in the years 1985-1986-1987. A control group of 66 cases was paired according to parity and episiotomy. The risk factors were identified as large fetal weight, instrumental deliveries, mid-line episiotomy or perineotomy. The questionnaires could be analysed for faults after delivery in 26 cases and 52 controls (response rate of 90%). The sole significant problem of the cases was perineal and rectal pain lasting more than a month longer than in the control cases. There was no greater dyspareunia, stress incontinence with urine, nor anal incontinence which contradicts previous reports in the literature. The authors conclude there are no serious complications of DCC following perineotomy providing repair is carried out very carefully. The patients in this group show that is was acceptable because no more in this group than in the controls were frightened of a repeat pregnancy. PMID- 8360447 TI - [Ectopic abdominal pregnancy. 2 cases treated by laparoscopic surgery]. PMID- 8360448 TI - [For sterilization is still illegal but insured]. PMID- 8360449 TI - [The autonomy of the practice of ultrasonography confirmed by the Court of Appeals (decision of 5 April 1993)]. PMID- 8360450 TI - A century of failure: health care reform in America. AB - To understand fully the persistent failure of the United States to enact national health insurance requires an appreciation not only of the role of government and the dynamics of politics but of underlying social realities. One consideration, which dates back to the Great Depression, is the absence of the middle class from a coalition in favor of such a policy. This absence reflects both the constricted vision of the middle class and the spirited campaigns of groups like Blue Cross to make certain that middle-class needs were met in order to reduce pressure for government intervention. Another critical social feature is the special entrepreneurial character of the American medical profession. Physicians saw themselves as small businessmen and, as such, shared and promoted a suspicion of governmental intervention. All the while, Americans justified the absence of a national program in terms of the ethos of voluntarism, which had a sufficient base in reality for the posture to be maintained without great embarrassment. In fact, the rhetoric that surrounded the enactment of Medicare reinforced these views, making it appear that, the elderly aside, all was well with the provision of medical services in the country. Even as national health insurance assumes a new prominence on the political agenda, it remains unclear whether these several considerations will allow for the enactment of sweeping changes. PMID- 8360452 TI - Black America: from community health care to crisis medicine. AB - This study traces the major policy shifts in medical care that have affected disadvantaged African-Americans and the response of this community's medical leadership to these changes. Since World War II policy has passed through three major phases. The first--engagement--ran from the mid-1960s through the mid 1970s. During this phase a community health policy orientation prevailed as national government targeted resources to health care programs for needy blacks and other poor Americans. From the late 1970s to the mid-1980s the period of submersion occurred: black community health professionals and political leaders experienced a new-found inclusion in health policy debate, but, at the same time, broader policy-making circles in government and health care reduced medical resources for the inner-city poor. Finally, in the third phase--crisis recognition--a network developed of community health advocates who seek to reorient the health system so that it addresses needs within urban American's "New Ghettos." PMID- 8360451 TI - The struggle for the soul of health insurance. AB - The politics of American health insurance is a struggle over which vision of distributive justice should govern: the solidarity principle or the logic of actuarial fairness. Actuarial fairness is central to American private health insurance. It is both an antiredistributive ideology and a method of organizing mutual aid by fragmenting communities into ever-smaller, more homogeneous groups, leading ultimately to the destruction of mutual aid. This fragmentation is accomplished by fostering in people a sense of their differences and their responsibility for themselves, rather than their commonalities and interdependence. Actuarial fairness developed as a business strategy for gaining market share. Medical underwriting, which is far more extensive than commonly known, is the information technology used for implementing actuarial fairness. Despite significant changes in the political context of health insurance which are leading toward restraints on underwriting, the logic of actuarial fairness is so deeply embedded in the structure of competitive markets in insurance and so deeply consonant with social divisions in American society that eradicating it will take more than any current reform proposals contemplate. PMID- 8360453 TI - Dogmatic slumbers: American business and health policy. AB - For more than a decade students of health policy have predicted a revolution waged by corporate purchasers of health care who would rise in demand of public policy cures for increasing and burdensome health care costs. This forecast has been largely disappointed, however, as the business sector has remained oddly diffident in its demands for health policy reform. There are three reasons for business's reticence--the economic stakes of the corporate sector in health reform are uncertain, organizational encumbrances hamper business activism in this arena, and ideological convictions make business wary of governmental solutions. Although business is sometimes said to manipulate the policy process for its own material ends, in the health sphere the most likely road to reform may reverse this image: a newly activist federal government may have to mobilize business support for reforms that advance both corporate interests and larger social goals. PMID- 8360454 TI - Together again: business, government, and the quest for cost control. AB - Corporate America leads the pack in the collective anxiety attack over health care costs. But will the business community add its considerable political power to the movement for national health reform? Conventional wisdom suggests not: businessmen seldom rally for collective concerns, have traditionally been biased against government action, and have diverse interests. This article guardedly offers grounds for greater optimism about corporate participation, arguing that the proper institutional context can help businessmen to see their preferences as consistent with health reform. Business groups have already proven critical to the issue development stage, where a dedicated group of corporate health reformists were key to getting reform on the national agenda. Business may also respond to strong leadership from President Clinton and assist in the legislation of national health reform. Yet the price of this corporate support is a decidedly conservative slant to the proposed legislation. PMID- 8360455 TI - Political influence in the 1990s: from iron triangles to policy networks. AB - To assess the prospects of comprehensive health care reform during the Clinton administration, we must examine the changes that have occurred in the political and structural contexts in which reform is debated. The political context includes the status of the health care system itself as well as public attitudes and voting patterns associated with health care reform; it may be friendlier now to reform than it has been in any previous period, but it cannot on its own produce policy change. The structural context, the representational community of organized interests and government institutions, is the means by which politics is either thwarted or translated into action. Changes in these organized interests and in Congress have transformed the health care reform policy community from an "iron triangle" dominated by an antireform alliance of medicine, insurance, and business to a more loosely bound policy network in which a reform coalition may now be able to prevail, especially under the direction of an activist president like Bill Clinton. I consider three hypotheses: The first claims that, despite the apparent structural changes, the core power relationships will remain the same as in the past, and the antireform alliance either will continue to block policy change or will push through a reform program that protects its constituent interests. According to the second, the structural changes produce an atomization of power, making coalition building in support of reform impossible. The third and most plausible hypothesis proposes that the structural changes, in combination with the shift in politics and Clinton's election, have generated new opportunities for fundamental reform. PMID- 8360456 TI - The courts, health care reform, and the reconstruction of American social legislation. AB - Because of budgetary and other political pressures, American health care reform (and other social reform) legislation is often not enforced, or is implemented in ways that undermine its egalitarian goals. About 25 years ago the federal courts began to try to reduce this gap between statutory promise and policy reality by interpreting federal funding laws as creating rights for their ultimate beneficiaries, including low-income patients and the providers who serve them. This major innovation in the concept of legal rights was confirmed by hundreds of judicial decisions and accepted by Congress itself. Over the past few years, however, a new Supreme Court, led by Chief Justice William Rehnquist, has issued opinions denying that such rights exist and vastly increasing agency power to reduce important statutory provisions to virtually meaningless formalities. Thus, at the very moment that national health care reform is prominent on the political agenda, the federal courts are abandoning a rights-enforcing role that may be critical for the reform's success. This article explains the struggle around the courts' rights-enforcing role, defends the role, and suggests ways that it can be maintained even if the courts themselves are not currently in a good position to fulfill it. PMID- 8360457 TI - The American states and Canada: a comparative analysis of health care spending. AB - Most comparisons of the relative effectiveness of cost containment in the Canadian and U.S. health systems trace Canada's greater success to its single payer approach. However, these studies ignore the substantial variation that exists in hospital and personal health care spending among both the American states and the provinces and territories of Canada. Four American states have adopted all-payer hospital rate setting; one other uses competitive bidding. All five show rates of growth in per capita hospital spending comparable to (and in some cases, lower than) the Canadian jurisdictions. Hospital spending, as a percentage of state gross domestic product (GDP), declined or remained constant in four of the five states. In four out of the five, growth in per capita spending on personal care, as a percentage of GDP, remained or fell below the national average. By contrast, in Canada, per capita spending on both hospitals and personal health care increased as a percentage of GDP in ten out of eleven jurisdictions. In each of the U.S. states, government played a central role in structuring the terms of payment and thus strengthened the hand of purchasers over providers. This strategy, rather than specifically a single-payer or universal health insurance approach, seems to be the key to limiting the growth in health costs to the growth in state or national income. PMID- 8360458 TI - Regulatory regimes and state cost containment programs. PMID- 8360459 TI - States and the health care crisis. PMID- 8360460 TI - Disinfection of medical waste. PMID- 8360461 TI - Biological indicators for a liquid chemical sterilizer: a solution to the instrument reprocessing problem? PMID- 8360462 TI - Nosocomial infections in neutropenic cancer patients. AB - OBJECTIVE: Identification of overall and site-specific rates of nosocomial infection in neutropenic patients with cancer and associated pathogens. DESIGN: Cumulative continuous prospective surveillance over a 42-month period. Criteria and definitions of infection in neutropenic patients (absolute neutrophil counts < 1,000/mm3) were developed, and surveillance was carried out by a certified infection control nurse and a senior oncology research fellow. SETTING: A cancer research center with two designated oncology nursing units. PATIENTS: Neutropenic patients with hematological and solid malignancies undergoing high-dose chemotherapy with and without autologous bone marrow transplantation. All patients admitted to both of the units during the study period were surveyed. Those who developed neutropenia are included in this report. RESULTS: A total of 444 nosocomial infections were identified in 920 neutropenic patients during 9,582 days of neutropenia for an overall rate of 48.3 per 100 neutropenic patients, or 46.3 per 1,000 days at risk. The rate of bloodstream infection per 100 neutropenic patients was 13.5 (gram-positive, 9.2; gram-negative, 4.8; and Candida 1.2). Other site-specific rates were: urinary tract, 5.7; respiratory tract, 5.5; thrush, 6.6; skin, 3.4; and gastrointestinal tract, 3.4. Among 392 pathogens identified, there were 137 (35%) gram-positive cocci, 105 (27%) gram negative rods, 70 (18%) Candida, 37 (9%) gram-positive rods, 22 (6%) viruses, and 15 (4%) Aspergillus. CONCLUSIONS: The rate of both overall and site-specific nosocomial infections in neutropenic patients is high. Neutropenia is a significant intrinsic risk factor that should be addressed in surveillance programs. Infection control and infectious diseases practitioners may need to modify techniques for surveillance, control, and management of infection in this population. PMID- 8360463 TI - Methicillin-resistant Staphylococcus aureus in a nursing home and affiliated hospital: a four-year perspective. AB - OBJECTIVES: To determine the effect of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak in a nursing home on the subsequent MRSA caseload in a closely affiliated hospital. DESIGN: Observational and descriptive; routine and special MRSA surveillance data for nursing home and hospital were reviewed for a four-year period (1988 to 1991) as were records regarding patient transfers from nursing home to hospital. SETTING: The 120-bed nursing home care unit (NHCU) and the geographically separate 434-bed acute care facility (hospital) of the Portland Veterans' Affairs Medical Center (PVAMC). PATIENTS: Veterans hospitalized in the acute care division of NHCU. RESULTS: Following the introduction of MRSA into the NHCU in December 1987, it quickly disseminated. Two to 32 newly colonized or infected patients were recognized in each quarter of the study period. Facility-wide prevalence surveys on two occasions disclosed MRSA colonization rates of 34% and 10%. During the study period, 15 to 54 (mean: 37.6) patients were transferred each quarter from the NHCU to the hospital of the PVAMC. The number of MRSA cases transferred ranged from 0 to 16 per quarter (mean: 5.4). During the same period, the total number of MRSA cases in the hospital increased, rising from 7 cases in 1987 to 16 in 1988, 48 in 1989, 34 in 1990, and 35 in 1991. The percentage of hospital MRSA cases accounted for by NHCU transfers was 0% in 1988, 38% in 1989, 12% in 1990, and 11% in 1991. CONCLUSIONS: Despite the steady flow of patients between the NHCU and the hospital, the MRSA outbreak in the NHCU was associated with only a modest increase in the MRSA caseload at the affiliated hospital. PMID- 8360464 TI - Choices: a brief review of economic analysis. PMID- 8360465 TI - Practicing emporiatrics: basic sources of information on travel medicine. AB - Travel medicine is an exciting and rewarding field. This article has provided an overview of basic sources of information. The interested clinician will find many other sources of information on special topics or on travelers with special medical conditions. PMID- 8360466 TI - New AIDS research institute opens in San Francisco. PMID- 8360467 TI - NIH opens first trial of HIV vaccines in children. PMID- 8360468 TI - Court rules on patient's right to file suit for fear of contracting HIV from surgeon. PMID- 8360469 TI - Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow. RB6 8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family. AB - Mouse Ly-6 proteins are characterized by lineage-restricted patterns of expression on lymphoid cells. A mAb (1A8) was produced to Ly-6G, a newly described member of the Ly-6 locus. Based on selective reactivity to cloned Ly-6 gene products expressed in EL4J cells, 1A8 was determined to be specific for Ly 6G. Furthermore, mAb to other Ly-6 specificities did not bind to Ly-6G transfected EL4J cells, indicating that Ly-6G is distinct from other serologically defined Ly-6 specificities. FACS analysis using 1A8 demonstrated that Ly-6G was expressed in bone marrow but not substantially on other lymphoid tissues, including activated T and B cells. In the bone marrow, Ly-6G expression was primarily restricted to the cells with more forward angle light scatter, which are mostly granulocytes. The RB6-8C5 mAb, previously described to detect a myeloid-restricted Ag (Gr-1) on more differentiated granulocytes, also reacted with Ly-6G- and Ly-6C-transfected EL4J cells. Both 1A8 and RB6-8C5 selectively precipitate a M(r) 21 to 25 kDa, glycosylphosphatidylinositol-anchored protein. Collectively, these data indicate that the Gr-1 Ag is a member of the Ly-6 family and further link expression of individual Ly-6 genes with distinct lineages in mouse bone marrow cells. PMID- 8360470 TI - Alterations in lymphopoiesis after hematopoietic reconstitution with IL-7 virus infected bone marrow. AB - Murine bone marrow was infected with a helper-free recombinant retrovirus expressing the mIL-7 gene and used to reconstitute lethally irradiated hosts. Twenty-three percent of mIL-7 retrovirus-infected recipients became moribund within 4-16 wk posttransplant with splenomegaly and hyperplastic lymph nodes, elevated white blood cell counts, plus other noticeable abnormalities including, in one animal, lymphocytic ascites. FACS analysis of hematopoietic tissue in diseased mice revealed marked alterations in T cell subsets of spleen and lymph nodes. These differences in extrathymic tissues compared with control animals included increases in CD4(-)-CD8+ lymphocytes and most strikingly the appearance of large numbers of an unusual CD4(+)-CD8+ T cell population with other characteristics of immature thymocytes (CD3lo-Thy1(+)-HSAhi). 3H-thymidine incorporation assays performed on extrathymic lymphocytes from a lymph node or ascites of two affected mice showed high levels of proliferation in the absence of either CD3 cross linking or exogenous IL-7 stimulation. Interestingly, in contrast to the effects noted on peripheral lymphoid tissues, no alteration in thymic size was noted and the proportion of CD4(+)-CD8+ cells was generally decreased with corresponding increases in CD4+ or CD8+ or CD4(-)-CD8- cells. These results provide further evidence of the involvement of IL-7 in the development and proliferation of early T cells in vivo and point to the possibility of IL-7 involvement in extrathymic expansion of a primitive class of T cells, the functional nature of which remains to be elucidated. PMID- 8360471 TI - Glycopeptides bind MHC molecules and elicit specific T cell responses. AB - Carbohydrates are T cell independent antigens because they do not bind to MHC molecules. However, glycopeptides might potentially bind to MHC molecules via their peptide component for presentation to T cells. We have conjugated the disaccharide galabiose [Gal alpha (1-4)Gal beta] to the amino terminus of a T cell peptide determinant from hen egg-white lysozyme [HEL(52-61)]. The resulting glycopeptide (Gal2-52-61) and a nonglycosylated analogue containing tyrosine and glutamic acid at the amino-terminus (YE-52-61) bound equally well to purified I Ak. T cell hybridomas were produced after immunization with Gal2-52-61. Many of the T cell hybridomas were glycopeptide-specific and responded to Gal2-52-61 but not to nonglycosylated synthetic peptides or to HEL presented by APC, indicating that the carbohydrate moiety influenced T cell recognition. Recognition was lost with the amino terminal attachment of the disaccharide to a peptide six amino acids longer at the amino terminus than HEL(52-61). Recognition also was lost with peptides containing only a single galactosyl residue or with galabiose bound to a different I-Ak binding peptide. T cells directed to Gal2-52-61 recognized glycopeptides having significant variation in the disaccharide structure, such as HEL(52-61) glycopeptides carrying lactose, cellobiose, or hepta-o-acetylated galabiose. Peptide residues were important features of the T cell epitope; Ala substitutions of two critical T cell contact residues of HEL(52-61) (Tyr53 and Leu56) abrogated T cell reactivity to the glycopeptides without affecting binding to I-Ak. In conclusion, we propose that these T cells recognize a peptide conformation specific to glycopeptide-I-Ak complexes and that this recognition does not involve specific interaction between the carbohydrate moiety and the T cell receptor. PMID- 8360472 TI - Cytotoxic T cell responses to minor H-43 alloantigens in H-43a and H-43b mice. Distinctive MHC class I restriction specificity and clonal inactivation are inherent properties of the H-43 system. AB - Our previous studies demonstrated that CTL responses to the newly identified minor H-43a and H-43b alloantigens induced in H-43b and H-43a responder mice, respectively, utilized the same H-2Kb (Kb) MHC class I restriction element, whereas many allelic class I products were not utilized. Also, a single i.v. injection of H-43b recipient mice with spleen cells (SC) from H-43 congenic mice induced specific and lasting CTL tolerance to H-43a rather than priming. We have produced a H-43b C3H.AU mouse strain (H-2p), which we regard as H-43 congenic to the C3H.NB (H-2p, H-43a) strain. Using this strain we demonstrate that Kp and/or Dp alleles can serve as class 1 restricting elements in the CTL responses to H 43a and H-43b alloantigens. Injection of H-43a recipient mice with antigenic H 43b SC from the paired H-43 congenic abrogated the anti-H-43b CTL response, irrespective of MHC class I specificity, i.e., in the contexts of Kb and of Kp and/or Dp elements. A corresponding result was obtained upon injection of H-43b recipient mice with congenic H-43a SC. The tolerance-inducing capacity of H-43a congenic SC was so strong that injection of these cells into H-43b responders that had previously received immunogenic H-43a SC completely blocked the previously activated Kb-restricted memory CTL activity specific for the H-43a alloantigen. PMID- 8360473 TI - Pattern of potassium channel expression in proliferating B lymphocytes depends upon the mode of activation. AB - Ionic channel expression is highly regulated during mitogenesis. But it is not clear whether these regulations only follow intrinsic programs during the course of the cell cycle or if they also depend upon the external factors used to promote cell activation. B lymphocytes express two classes of potassium channels and can be stimulated to enter the cell cycle by distinct pathways. Thus, we have analyzed, with the patch-clamp technique, if the expression of channels varies when the cells are activated by different signals that lead to cell proliferation. We found that stimulation through Ag receptors increases the expression of calcium- and voltage-activated potassium channels, whereas a bacterial mitogen, LPS, only enhances the expression of the latter. Moreover, channel expression can still be modified in proliferating cells because stimulation of LPS-activated cells through Ag receptors induces rapid expression of calcium-activated channels. The use of inhibitors of mRNA synthesis revealed that this process depends upon gene transcription. Thus, differential induction of the expression of potassium channels is not only linked to the entry into the cell cycle but depends also on pathways of stimulation. PMID- 8360475 TI - Low concentrations of Gm allotypic subsets G3 mg and G1 mf in homozygotes and heterozygotes. AB - Serum concentrations of IgG3, IgG1, and of the Gm allotypic subsets of these two isotypes were measured in adult homozygotes and heterozygotes. Alleles G3 mb and G3 mst of the IgG3 locus, and alleles G1 ma and G1 max of the IgG1 locus were found to associate with a high concentration of the allotypic product. Alleles G3 mg (IgG3) and G1 mf (IgG1) were associated with a low concentration of the product. This was true regardless of the haplotype; for example, allele G3 mb was associated with a high concentration of the product in all haplotypes f;n+;b f;n ;b and fa;n+;b. One dose of allele G3 mg was associated with a characteristic mean concentration of the product (g-type IgG3). This rule was valid regardless of the other allele of the subject, thus, heterozygotes and G3 mg/g homozygotes had mean concentrations of 0.10 and 0.20 g/liter, respectively, of g-type IgG3. Products of the IgG1 alleles were also simply additive: one dose of allele G1 ma(x) or G1 mf was associated with mean concentrations of 3.63 and 2.84 g/liter, respectively, and two doses with twice these amounts. Only allele G3 mb did not completely follow this rule. We also studied the serum concentrations and the allotype distribution of 41 IgG1 and 31 IgG3 myeloma proteins. The results suggested that the allotype-associated differences in serum concentrations are caused by different numbers of B cells producing allotypic subsets of IgG1 or IgG3, not by different rates of synthesis per B cell. PMID- 8360474 TI - Properdin, a positive regulator of complement activation, is expressed in human T cell lines and peripheral blood T cells. AB - Properdin plays an important regulatory role in the activation of the complement system. Here we report the biosynthesis of properdin in four different human T cell lines and in T cells purified from peripheral blood. Cell sorting experiments, in conjunction with Northern blotting, showed that both CD4- and CD8 bearing populations of T cells have the potential to synthesize properdin. The functional activity of properdin secreted from these T cell lines was determined in a hemolytic assay. In view of the numerous ways in which complement activation may influence cellular immune response, the present results indicate, for the first time, a possible interaction between the complement and the T cell system. PMID- 8360476 TI - Expression of the Bcl-2 protein in murine and human thymocytes and in peripheral T lymphocytes. AB - Bcl-2, a proto-oncogene that can block apoptosis, was found to be expressed throughout the thymic medulla, but in only scattered cells in the thymic cortex. In order to determine the precise distribution of Bcl-2 protein during thymocyte development, we utilized mAb specific for either mouse or human Bcl-2. Thymocyte subpopulations were assessed using three-color flow cytometry and a saponin permeabilization method. Staining of adult mouse and human thymocytes was comparable, with 20 to 35% of cells expressing Bcl-2. Bcl-2 was expressed in nearly all CD4+ and CD8+, and CD3hi cells, but in only 5 to 10% of CD4+8+ cells. The CD4-8- population was more variable, with 25 to 40% of human cells and 65 to 80% of murine cells expressing Bcl-2. In sorted adult murine CD4-8- cells, the very immature Pgp-1+/IL-2R alpha- subset had a high percentage of Bcl-2+ cells. Bcl-2 expression was also examined during murine fetal development. At fetal day 15.5 to 16.5, 60 to 70% of total thymocytes expressed Bcl-2. By fetal day 17.5, overall Bcl-2 expression fell to adult levels of 20 to 30%. Bcl-2 was present in peripheral T cells from lymph node, spleen, and peripheral blood at uniformly high levels. In vitro stimulation with anti-CD3 or anti-TCR antibodies increased Bcl-2 expression in total thymocyte cultures, but could not induce Bcl-2 expression in CD4+8+ cells, even with the addition of a variety of cytokines. These data suggest that early double negative thymocytes express Bcl-2 but lose Bcl-2 with differentiation to the double positive stage. Thymocytes regain Bcl-2 during selection to a single positive state and retain Bcl-2 in the periphery. PMID- 8360477 TI - Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction. AB - IL-11 is a novel cytokine with a variety of biofunctions which overlap with those of IL-6. We have previously identified IL-11 specific binding protein which is distinct from that of IL-6 in a number of cell lines. The similarities in biofunctions and differences in ligand binding proteins between IL-11 and IL-6 prompted us to investigate whether IL-11 shares common signal transduction mechanisms with IL-6. We have examined early signals triggered by IL-11 or IL-6 in a multifactor-dependent human erythroleukemic cell line, TF-1. The results showed that IL-11 and IL-6 can both stimulate cell proliferation, induce similar pattern of protein tyrosine phosphorylation, and activate the same proto-oncogene (junB) expression in TF-1 cells. These findings imply that IL-11 and IL-6 share similar early signaling events with the possibility of using the same signal transducer, gp130. We next tested whether IL-11 induced signaling can be inhibited by anti-gp130 antibodies which blocked IL-6-mediated functions. It was observed that anti-gp130 antibodies abolished cell proliferation, protein tyrosine phosphorylation, and junB gene expression elicited by IL-11 or IL-6 in TF-1 cells. The same antibodies, however, had no effect on granulocyte-macrophage colony stimulating factor or erythropoietin-induced TF-1 cell proliferation. Finally, anti-IL-6R antibody inhibited the ability of IL-6, but not IL-11, to transduce early signals in TF-1 cells. These results demonstrate that IL-11 and IL-6 utilize different ligand binding proteins, but share common signal transducer, gp130, in TF-1 cells. PMID- 8360478 TI - Nonimmune macromolecular complexes of Ig in human gut lumen. Probable enhancement of antibody functions. AB - Protein Fv, a human sialoprotein recently described in the stools of patients suffering from liver diseases, binds the variable domain of H chains without impairing Ag binding. Normal subjects are shown here to secrete protein Fv under a hidden form, saturated with luminal Ig. In feces, the nonimmune complexes are essentially of 1800 and 800 kDa M(r); they contain protein Fv molecules bound with F(ab')2 fragments produced by cleavage of Secretory IgA during colonic transit. The 800-kDa complexes correspond to 6 molecules of F(ab')2 fragments bound to a sole protein Fv dimer. This was established by comparison with an in vitro-made complex having a valency of 6. Investigation of the role of protein Fv shows that in vitro addition of this free molecule to antivirus or to anti Salmonella typhi antibodies allows or augments agglutination of the corresponding pathogens. This property is of major interest for secretory antibodies because it favors their role in Ag conveyance in the mucus stream. It seems therefore that protein Fv is a novel key factor of the immune defense in gut. PMID- 8360479 TI - Characteristics of endogenous peptides eluted from the class I MHC molecule HLA B7 determined by mass spectrometry and computer modeling. AB - Microcapillary HPLC electrospray ionization tandem mass spectrometry was used to sequence 15 peptides eluted from HLA-B7. Sequence alignment implicated four peptide positions in specific interactions with the class I molecule, and their importance was confirmed using synthetic peptides. Because no crystal structure for HLA-B7 was available, computer-assisted modeling was used to understand novel aspects of peptide binding specificity and to accurately predict the effect of defined changes in peptide structure. The results demonstrate that mass spectrometric sequencing coupled with computer-assisted modeling can be used in the absence of a crystal structure to make accurate predictions concerning requirements for peptide binding to class I molecules. These techniques may be valuable to predict or engineer T cell epitopes. PMID- 8360480 TI - Coordinate silencing of myeloma-specific genes in myeloma x T lymphoma hybrids. AB - It has been well-established that Ig genes are transcriptionally silenced when Ig producing myeloma lines are fused to non-B cells. In the present study, we analyzed the expression of several other myeloma-specific genes in fusions of myelomas with the T lymphoma, BW5147. Seven of the eight genes analyzed behaved coordinately with the Ig loci; they were silent in most myeloma x T hybrids but active in the rare hybrid that retained Ig gene expression. Cloned IgH genes introduced into the two types of hybrids behaved as their endogenous counterparts. The coordinate behavior of these several genes in the panel of "exceptional" and "extinguished" hybrids suggests a central and bimodal switch for alternately activating and de-activating the genetic program of the Ig secreting plasmacyte. The switch between an active and an inactive transcriptional state involves, at some level, a change in the methylation status of the IgH genes. Methylation and transcriptional activity were inversely correlated. In Ig-extinguished hybrids the myeloma-derived locus was methylated de novo, whereas in the rare Ig-expressing hybrid, the T cell-derived locus was demethylated de novo. PMID- 8360481 TI - The soluble pool of beta 2-microglobulin free HLA class I alpha-chains. Qualitative and quantitative characterization. AB - Previous studies have demonstrated that HLA class I heterodimers are present in plasma and cell culture supernatants. They can be precipitated by mAb the binding of which is dependent on the proper association of the polymorphic alpha-chain with beta 2-microglobulin (beta 2-m). The molecular mass of the alpha-chain ranges from 45 to 35 kDa with a number of intermediate products. We report on the identification of 35-kDa soluble beta 2-m free HLA class I H chains immunoprecipitated by mAb LA45 from cell culture media of activated B and T cells. Furthermore, a peptide-based competitive immunosorbent assay was established to determine the amounts of soluble HLA class I alpha-chains. By means of this assay, we formally proved the specificity of mAb LA45 for a linear epitope on HLA class I H chains centered on residues arginine-asparagine at positions 62 and 63 of the alpha 1-domain. PHA or rIL-2 were identified as efficient stimuli for PBMC leading to the generation of soluble beta 2-m free HLA class I H chains. Testing of cell lines representing distinct stages of hematopoietic differentiation demonstrated a significant correlation between cell surface expression of beta 2-m free HLA class I H chains and amounts of soluble LA45 reactive molecules. However, three of six human T lymphotropic virus type I transfected cell lines, although expressing beta 2-m free H chains, do not generate soluble molecules. Finally, human sera were found to contain considerable amounts of beta 2-m free HLA class I H chains. The average amount of these molecules in sera of individuals with one positive LA45 allele was determined to be 46.9 +/- 38.6 nM/liter. PMID- 8360482 TI - Humanization of an antibody directed against IgE. AB - IgE antibodies bind to specific high-affinity receptors on mast cells, leading to mast cell degranulation and release of mediators, such as histamine, which produce symptoms associated with allergy. Hence, anti-IgE antibodies that block binding of IgE to its high-affinity receptor are of potential therapeutic value in the treatment of allergy. These antibodies must also not bind to IgE once it is bound to the receptor because this would trigger histamine release. This study describes the humanization of a murine antibody, MaE11, with these characteristics. Variants of the humanized antibody were evaluated to probe the importance of framework residues on antibody binding and to determine which charged residues in the CDR interacted with IgE. We found that only five changes in human framework residues were required to provide for binding comparable to that of the original murine antibody. PMID- 8360483 TI - Extraembryonic expression of the human MHC class I gene HLA-G in transgenic mice. Evidence for a positive regulatory region located 1 kilobase 5' to the start site of transcription. AB - Trophoblast, the only fetal tissue in direct contact with maternal cells, fails to express the polymorphic HLA class I molecules HLA-A and -B, but does express the nonpolymorphic class I molecule HLA-G. It is thought that HLA-G may provide some of the functions of a class I molecule without stimulating maternal immune rejection of the fetal semiallograft. As a first step in identifying the cis acting DNA regulatory elements involved in the control of class I expression by extraembryonic tissue, several types of transgenic mice were produced. Two HLA-G genomic fragments were used, 5.7 and 6.0 kb in length. These included the entire HLA-G coding region, 1 kb of 3' flanking sequence, and 1.2 or 1.4 kb of 5' flanking sequence, respectively. A hybrid transgene, HLA-A2/G, was produced by replacing the 5' flanking sequence, first exon, and early first intron of HLA-G with the corresponding elements of HLA-A. Comparison of transgene mRNA expression patterns seen in HLA-A2/G and HLA-G transgenic mice suggests that 5' flanking sequences are largely responsible for the differing patterns of expression typical of the classical class I and HLA-G genes. Studies comparing the extraembryonic HLA-G expression levels of founder embryos transgenic for either the 5.7- or 6.0-kb HLA-G transgene showed that the 6.0-kb transgene directed HLA G expression far more efficiently than did the 5.7-kb HLA-G transgene, producing extraembryonic HLA-G mRNA levels similar to those seen in human extraembryonic tissues. The results of these studies suggest that the 250-bp fragment present at the extreme 5' end of the 6.0-kb HLA-G transgene and absent from the 5.7-kb HLA-G transgene contains an important positive regulatory element. This 250-bp fragment lies further upstream than any of the previously documented class I regulatory regions and may function as a locus control region. PMID- 8360484 TI - Regulation of TL antigen expression. Analysis of the T18d promoter region and responses to IFN-gamma. AB - Type I (alpha/beta) and type II (gamma) IFN enhance MHC class I gene expression through an IFN-responsive element (IRE) present in the 5' flanking region of the class I-a genes. Comparison of the 5' sequences between classical class I-a genes and T region class I-b genes reveals little homology except for presence of a potential IRE. We have found that cell surface expression of thymus leukemia Ag (TL) was up-regulated by IFN-gamma to a greater extent than H-2K,D in all TL+ T cell lines tested. In contrast, IFN-alpha/beta, which significantly increased H 2K and H-2D Ag expression, had only minor effects on TL expression. Resting peripheral T cells, which were considered to be TL- from previous studies, were found to express TL at a low level as determined by flow cytometry, immunoprecipitation, as well as polymerase chain reaction; the level of expression also could be elevated by IFN-gamma. To examine the control of TL gene transcription and its regulation by IFN-gamma, varying lengths of the T18d 5' flanking region were analyzed in chloramphenicol acetyl transferase assays. By deletion analysis, promoter activity and IFN-gamma responsiveness were localized to an 86-bp fragment that contains the IRE. Both responses were localized further to a 32-bp fragment that contained the IRE at its 3' end. RNase protection assays revealed two major transcription initiation sites, one immediately 5' of the IRE and another approximately 60 bp downstream. Furthermore, polymerase chain reaction analysis of mRNA from resting T cells, thymocytes, and T cell tumor lines confirmed the RNase protection data. Thus, transcription of T18d initiates much further upstream than the classical class I genes, can utilize an unusual promoter element, and can be elevated by IFN-gamma. PMID- 8360485 TI - IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. AB - Normal melanocytes require a number of exogenous growth factors in contrast to most metastatic malignant melanomas. This investigation demonstrates that endogenously produced human IL-8 can act as an important growth factor for human melanoma cells. In the present study, six out of eight human melanoma cell lines tested secrete IL-8 protein into the culture supernatant. In two of these IL-8 secreting melanoma cell lines, SK-MEL 13 and SK-MEL 23, we have determined the IL 8 requirement for their proliferative capacity. These melanoma cell lines produced significant amounts of bioactive IL-8 as measured by the ELISA technique. Secretion of human IL-8 was inducible by IL-1 and by PMA. Human IL-8 specific mRNA was already detected in unstimulated melanoma cells. In addition, human IL-8-R mRNA could be detected for the first time in human melanoma cells. Exposure of the two melanoma cell lines in vitro to antisense oligonucleotides targeted against two different sites of human IL-8 mRNA-inhibited cell proliferation, colony formation in soft agar, and secretion of IL-8 protein into culture supernatant in a dose dependent fashion. Effects were reversible either by removal of the oligomers or by addition of exogenous IL-8 protein. In contrast, exposure to IL-8 sense probes or oligonucleotides in sense or antisense orientation specific for IL-7, TGF-alpha, TGF-beta, and MGSA had no such effect. A monospecific immune serum and two IL-8-specific mAb were also capable of inhibiting melanoma cell proliferation in the same manner. These results provide strong evidence for an autocrine IL-8 synthesis and for an IL-8-dependent proliferation in a subgroup of human melanomas. Furthermore, they suggest that IL 8 may play a role not only in immunomodulation but also in melanoma progression and metastatic spread. PMID- 8360486 TI - Analysis of human skin mast cell proteins by two-dimensional gel electrophoresis. Identification of tryptase as a sialylated glycoprotein. AB - Proteins of mast cells purified from human foreskin were separated by 2-D polyacrylamide gel electrophoresis using either nonequilibrium pH gradient electrophoresis or isoelectric focusing in the first dimension and SDS-PAGE in the second dimension. Silver staining showed that a major feature of skin mast cell 2-D protein maps was a variety of relatively abundant proteins in the m.w. range of 29 to 37 kDa and covering a broad pH range from 5.0 to 8.5. Tryptase was identified on Western blots of 2-D-separated proteins by its binding of mAb and of 3H-diisopropylfluorophosphate. The precise distribution of tryptase varied among individuals but this protein generally occupied a continuum of molecular weights between 28 and 37 kDa and ranged in isoelectric point between 5.0 and 6.5. Tryptase was one of a number of mast cell proteins that bound the lectin concanavalin A as well as lectins specific for sialic acid, demonstrating that this enzyme is a sialylated glycoprotein. The diffuse m.w. distribution of skin mast cell tryptase (31 to 36 kDa) observed after SDS-PAGE was reduced to a single band of 30 kDa after treatment with protein-N-glycosidase F to remove asparagine linked oligosaccharides. This finding suggests that intrinsic m.w. heterogeneity of tryptase in skin mast cells is largely a result of the addition of variable amounts of oligosaccharide to the tryptase polypeptide. PMID- 8360487 TI - IL-2 up-regulates but IFN-gamma suppresses IL-8 expression in human monocytes. AB - IL-2 has pleiotropic properties and is a potent activator of monocytic functions. Since monocytes are an important source of the chemoattractant cytokine IL-8, we studied the effects of IL-2 on the expression of IL-8 in human monocytes. IL-8 mRNA expression was detectable in resting human monocytes. Treatment of monocytes with IL-2 increased IL-8 mRNA expression by a protein synthesis-independent process. The augmentation of IL-8 mRNA by IL-2 was associated with an increase in IL-8 secretion. The expression of IL-8 mRNA was not a nonspecific response to any stimulus of monocyte activation. In fact, IFN-gamma, which is also a potent monocyte activator, not only failed to induce IL-8 expression but inhibited the stimulation of IL-8 by IL-2. Nuclear run-on experiments demonstrated that both the enhancement of IL-8 mRNA expression and its down-regulation by IFN-gamma occurred at the transcriptional level. These results show for the first time that in fresh human monocytes, IL-8 expression is differentially regulated by IL-2 and IFN-gamma and suggest that the interactions among IL-2, IL-8, and IFN-gamma may be important for the development and control of the inflammatory response. PMID- 8360488 TI - Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein. AB - We have previously shown that a synthetic peptide (CKS-17) homologous to retroviral envelope protein suppresses the accumulation of superantigen staphylococcal enterotoxin-induced TNF-alpha mRNA in human PBMC and in highly purified human monocytes. The present study was designed to examine the underlying mechanism(s) by which CKS-17 down-regulates the TNF-alpha mRNA expression using a human acute monocytic leukemia cell line THP-1 stimulated with the superantigen staphylococcal enterotoxin E. A cyclooxygenase inhibitor indomethacin does not reverse the inhibition of TNF-alpha mRNA expression by CKS 17, suggesting that prostaglandins are not responsible for the suppressive action of CKS-17. The inhibitory effect of CKS-17 is, however, significantly blocked by a protein synthesis inhibitor cycloheximide, indicating that CKS-17 requires de novo protein synthesis to induce the suppressive activity. The mRNA stability assays using actinomycin D show that CKS-17 does not decrease the TNF-alpha mRNA stability. Nuclear run-on transcription assays further reveal that CKS-17 suppresses the TNF-alpha mRNA transcription rate. Taken together, these results suggest that the synthetic retroviral peptide CKS-17 down-regulates TNF-alpha mRNA expression through inhibition of transcriptional activation of the TNF-alpha gene, which requires de novo synthesis of a transcriptional repressor protein(s). PMID- 8360489 TI - Particle opsonization and lung macrophage cytokine response. In vitro and in vivo analysis. AB - Inhaled inert particles and organisms cause a spectrum of pulmonary responses, ranging from minimal changes to marked acute inflammation. During ingestion and clearance of such particles, alveolar macrophages (AM) can initiate pulmonary inflammation by production of TNF and neutrophil chemoattractant cytokines. We tested the role of opsonization in determining the AM response to ingestion of inert particles in vitro and in vivo. As measures of AM activation after phagocytosis in vitro, we measured release of TNF and mRNA expression for the platelet-factor 4 family neutrophil chemoattractants, KC and macrophage inflammatory protein-2 (MIP-2). Using albumin-coated fluorescent latex particle as phagocytic targets, we found a marked release of TNF by AM ingesting particles opsonized with antialbumin IgG, although uptake of similar numbers of unopsonized particles caused little or no release (e.g., 4648 +/- 1147 pg/ml, opsonized beads vs 576 +/- 205 unopsonized, 10:1 particle:cell ratio, n = 4, mean +/- SD). Flow cytometry confirmed equal uptake of the two particle types. Northern analysis of AM mRNA showed marked induction of KC and MIP-2 mRNA after ingestion of opsonized particles only. Instillation of opsonized particles into hamster lungs caused a marked neutrophil influx, although unopsonized particles did not. TNF was elevated in lavage fluid after instillation of opsonized particles, but not after unopsonized beads (92.7 +/- 136 pg/ml opsonized, n = 7 vs 1.3 +/- 3.6 unopsonized, n = 6). KC and MIP-2 mRNA were induced in lavaged cells after instillation of opsonized but not after unopsonized particles or vehicle control. The nature of particle interaction with the AM surface during phagocytosis determines the subsequent AM response. Although many unopsonized inert particles are ingested with minimal AM activation, specific opsonization of pathogens or non-specific adsorption of Ig onto other particles may activate AM and lead to pulmonary inflammation. PMID- 8360490 TI - Effects of subunit mutation on the localization to coated pits and internalization of cross-linked IgE-receptor complexes. AB - IgE receptors of mast cells, Fc epsilon RI, localize to coated pits and internalize after cross-linking. We investigated whether any one of the receptor's four distinctive cytoplasmic domains regulates these phenomena. COS cells, which lack Fc epsilon RI entirely, and P815 mouse mastocytoma cells that lack the alpha and beta subunits of the tetrameric Fc epsilon RI (alpha beta gamma 2), were transfected with wild-type, incomplete, or variant Fc epsilon RI. IgE-receptor complexes were observed by electron microscopy. Before cross-linking with anti-IgE gold particles, receptors were not preferentially localized to coated pits, which occupy approximately 1% of the cell surface. After cross linking, up to 10 to 20% of the wild-type and most other receptor variants were in coated pits in transfected P815 cells at any one time. beta-less variants localized normally but, surprisingly, receptors containing a variant beta subunit showed reduced localization. "Receptors" consisting simply of the lipid-anchored ectodomains of the human alpha subunit failed to localize to coated pits. In general, cross-linked receptors that localized to coated pits were progressively internalized, whereas receptors that failed to accumulate in coated pits were not. We conclude that no single cytoplasmic domain of the Fc epsilon RI uniquely controls its ligand-induced localization to coated pits and internalization. PMID- 8360491 TI - Human mononuclear phagocytes express adenosine A1 receptors. A novel mechanism for differential regulation of Fc gamma receptor function. AB - Using monoclonal anti-adenosine A1 receptor antibodies that bind the A1 receptor ligand binding site, we demonstrate that A1 receptors are expressed on cultured monocytes and rheumatoid synovial fluid mononuclear phagocytes. This finding is associated with the acquisition of reactivity with selective adenosine A1 receptor agonists and is temporally coordinated with the induction of adenosine A2 receptors on cultured monocytes. In a rapid, concentration-dependent fashion, these two distinct adenosine receptors modulate Fc gamma receptor-mediated phagocytosis, a response critical to the pathogenesis of immune complex diseases. Occupancy of A1 receptors by N6-cyclopentyladenosine (an A1-specific adenosine analogue) or mAb AA1 (an anti-A1 mAb) results in a potent stimulation that is blocked by adenosine receptor antagonists. This A1 receptor-induced enhancement of Fc gamma receptor-mediated phagocytosis is a consequence of preferential augmentation of Fc gamma RI function, suggesting distinct mechanisms for receptor effector coupling of Fc gamma receptor families. In contrast, ligation of A2 receptors by A2-specific agonists decreases Fc gamma receptor-mediated phagocytosis in cultured monocytes. The opposing effects of adenosine A1 and A2 receptors allow for a concentration-dependent feed-back loop that responds more rapidly than effects elicited by other endogenous modulators. Low concentrations of adenosine are proinflammatory providing enhanced Fc gamma receptor function via A1 receptors, whereas higher concentrations that can occur with tissue damage are anti-inflammatory providing inhibition via A2 receptors. This rapid and potent modulation of Fc gamma receptor-mediated function suggests that adenosine is an important local regulator of the inflammatory response. PMID- 8360492 TI - Synergism between human monocyte chemotactic and activating factor and bacterial products for activation of tumoricidal properties in murine macrophages. AB - Chemotactic factors regulate the recruitment of monocytes-macrophages to inflammatory sites and neoplastic tissues. The purpose of this study was to determine whether MCAF also influences the activation of C3H/HeN macrophages to become tumoricidal. Several metastatic and nonmetastatic clones of the K-1735 murine melanoma cells syngeneic to C3H/HeN mice were transfected with expression vectors containing the human MCAF gene or control DNA. Tumor cells producing high levels of MCAF were significantly lysed by macrophages treated with LPS, whereas parental or control transfected cells were not. Control-activated macrophages incubated with both IFN-gamma and LPS lysed all the melanoma cells regardless of MCAF production. Pretreatment of macrophages with MCAF significantly enhanced their response to low concentrations of LPS, muramyl tripeptide, and a synthetic bacterial LPP, as measured by lysis of murine melanoma cells. These data suggest that in addition to being a chemotactic factor, MCAF can prime macrophages to respond to endotoxins and other bacterial products and therefore may regulate several levels of macrophage-tumor interactions in situ. PMID- 8360493 TI - Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells. AB - Highly conserved DBP (human DBP is known as Gc) of serum alpha 2-globulin fraction can be converted to a potent macrophage activating factor by stepwise modification of Gc glycoprotein with beta-galactosidase of B cells and sialidase of T cells. These glycosidases, beta-galactosidase and sialidase, are membrane bound and not soluble in culture medium. Thus, consecutive contact of Gc protein with B cells and T cells, presumably via specific receptors, is required for conversion of Gc glycoprotein to the macrophage activating factor. The essential role of T cell sialidase in macrophage activation was confirmed by the finding that peritoneal nonadherent cells of SM/J mouse, whose T cells are deficient in sialidase activity, were unable to convert Gc protein to the macrophage activating factor and thus did not activate macrophages. Treatment with sialidase of a conditioned medium of lipid metabolite-treated SM/J mouse nonadherent cells efficiently generated the macrophage activating factor. When Gc protein was first treated with soluble or immobilized sialidase and used in a medium for 2 h cultivation of lipid metabolite-treated SM/J mouse nonadherent cells or BALB/c mouse B cells, the resultant conditioned media contained a large amount of the macrophage activating factor. These results support the hypothesis that Gc protein carries a dibranched trisaccharide with galactose and sialic acid termini. PMID- 8360494 TI - Differential expression of H-2K and H-2D in the central nervous system of mice infected with Theiler's virus. AB - A model of demyelination induced by Theiler's murine encephalomyelitis virus (TMEV) was used to study differential regulation of class I MHC gene products in the brain and spinal cord of resistant (B10) and susceptible (B10.Q and B10.RBQ) mice. Allelic polymorphisms in the H-2D region, but not the H-2K region, play a primary role in determining susceptibility to late demyelinating disease. However, even though significant structural diversity distinguishes class I alleles, there are no discernible K or D-specific patterns of structural diversity within the peptide binding domains of these glycoproteins. Our hypothesis was that D region association of susceptibility to demyelination was related to differences in the expression of the K and D Ag in the central nervous system (CNS) after TMEV infection. Using allele-specific mAb and an immunoperoxidase technique, we demonstrated transient but equivalent increases in K and D Ag expression in the brain and spinal cord of resistant mice beginning 7 days after TMEV infection, which returned to baseline by 90 days. However, when genetically susceptible animals were examined, a significantly greater increase in D expression relative to K expression was seen in the brain and spinal cord at all post-infection observation periods. Immunosuppression of genetically resistant animals before TMEV infection, which results in viral persistence, was accompanied by equivalent increases in both the K and D Ag. Depletion of CD8+ T cells, but not CD4+ T cells, in susceptible mice ablated class I expression in the CNS in response to TMEV infection, implying that CD8+ cells contribute to the differential regulation of K and D Ag in the CNS. These findings are consistent with the hypothesis that differences in gene regulation may account for different roles of the K and D loci play in determining resistance and susceptibility to TMEV-induced demyelinating disease. PMID- 8360495 TI - High affinity, thyroid-specific human autoantibodies displayed on the surface of filamentous phage use V genes similar to other autoantibodies. AB - Autoantibodies to thyroid peroxidase (TPO) are characteristic of thyroid inflammation in autoimmune thyroid disease. We have used the phage display, H and L chain combinatorial cDNA library approach to clone, from thyroid-infiltrating B cells, six new human Fab autoantibodies with high affinities (approximately 10( 10) M) for TPO. This library, in the pComb3 vector, was screened with viable, stably transfected Chinese hamster ovary cells expressing human TPO on their surface. The H and L chain genes in the six TPO-specific Fab were similar, but not identical, to those encoding Fab previously isolated from the same library by screening bacteriophage plaques in the Immunozap vector with purified TPO. The TPO-specific VK genes isolated with the phage display system are closer to germline than those obtained with Immunozap. Essentially all the V kappa isolated with pComb3 were 99 or 100% homologous with the germ-line genes KL012 and A3 that also code for low affinity systemic autoantibodies. There are two important implications of the study. First, the phage display system can be used with impure Ag to generate high affinity autoantibodies. This finding opens the way to cloning autoantibodies against other autoantigens, not previously possible with the bacteriophage lambda approach because of the lack of purified Ag. Second, germ-line L chain genes can code for very high affinity antibodies. PMID- 8360497 TI - Induction of antibodies to a kappa V region by gene immunization. AB - Direct gene transfer into muscle can lead to sustained gene expression at the injected sites. Here we tested the ability of in vivo gene transfection to immunize mice against an isolated human IgV region. The Humkv325 germline kappa L chain V gene encodes the kappa L chain in V regions of several human IgM autoantibodies and is used frequently in chronic lymphocytic leukemia. This gene was inserted into a mammalian expression vector, pREP7, to produce pREVk3. Mice injected i.m. with pREVk3 produced antibodies against the V region of Glo, a human monoclonal IgM paraprotein whose kappa L chain is encoded by Humkv325. Co injection of an expression vector encoding IL-2 enhanced anti-Glo antibody production fivefold and induced a localized delayed hypersensitivity reaction. Antibody production also was induced when vectors encoding Humkv325 and IL-2 were injected s.c. These experiments demonstrate that gene immunization vectors can stimulate immune responses to antibody V region determinants. PMID- 8360498 TI - Nomenclature for T-cell receptor (TCR) gene segments of the immune system. WHO IUIS Nomenclature Sub-Committee on TCR Designation. AB - The recommended procedures and criteria for T-cell receptor (TCR) designations are described. The officially adopted designations are for the TCR A, B, D and G loci and for V, D, J and C segments. PMID- 8360496 TI - Macrophage inflammatory protein-1 alpha expression in interstitial lung disease. AB - Mononuclear phagocyte (M phi) recruitment and activation is a hallmark of a number of chronic inflammatory diseases of the lung, including sarcoidosis and idiopathic pulmonary fibrosis (IPF). We hypothesized that macrophage inflammatory protein-1 (MIP-1 alpha), a peptide with leukocyte activating and chemotactic properties, may play an important role in mediating many of the cellular changes that occur in sarcoidosis and IPF. In initial experiments, we demonstrated that human rMIP-1 alpha exerted chemotactic activities toward both polymorphonuclear leukocytes and monocytes, and these activities were inhibited by treatment with rabbit anti-human MIP-1 alpha antiserum. In support of the potential role of MIP 1 alpha in interstitial lung disease, we detected MIP-1 alpha in the bronchoalveolar lavage fluid of 22/23 patients with sarcoidosis (mean 443 +/- 76 pg/ml) and 9/9 patients with IPF (mean 427 +/- 81 pg/ml), whereas detectable MIP 1 alpha was found in only 1/7 healthy subjects (mean 64 +/- 64 pg/ml). In addition, we found a 2.5- and 1.8-fold increase in monocyte chemotactic activity in BALF obtained from patients with sarcoidosis and IPF respectively, as compared to healthy subjects, and this monocyte chemotactic activity, but not neutrophil chemotactic activity, was reduced by approximately 22% when bronchoalveolar lavage fluid from sarcoidosis and IPF patients were preincubated with rabbit antihuman MIP-1 alpha antibodies. To determine the cellular source(s) of MIP-1 alpha within the lung, we performed immunohistochemical analysis of bronchoalveolar lavage cell pellets, transbronchial biopsies, and open lung biopsies obtained from patients with IPF and sarcoidosis. Substantial expression of cell-associated MIP-1 alpha was detected in M phi, including both alveolar AM phi and interstitial M phi. In addition, interstitial fibroblasts within biopsies obtained from sarcoid and IPF patients also expressed immunoreactive MIP-1 alpha. Minimal to no detectable MIP-1 alpha was expressed in alveolar M phi from healthy subjects or interstitial cells in lung biopsy specimens obtained from patients undergoing thoracotomy for malignancy. Furthermore, pulmonary fibroblasts isolated from patients with IPF produced greater amounts of MIP-1 alpha after challenge with IL-1 beta than did similarly treated pulmonary fibroblasts recovered from patients without fibrotic lung disease. Our findings suggest that MIP-1 alpha is expressed in increased amounts within the airspace and interstitium of patients with sarcoidosis and IPF, and that this cytokine may be an important mediator of both M phi activation and recruitment that characterize these disease states. PMID- 8360499 TI - Microtiter plate assay for measuring the anticomplementary activity of immunoglobulins. AB - An anticomplementary activity (ACA) assay on a microtiter plate combined with a computer-controlled plate reader and computerized calculation of the assay result is described. The assay is a simplified version of existing ones and can be used to assay immunoglobulins at low protein concentrations. The method detects the consumption of 0.13 CH50U, corresponding to anticomplementary activity of 7.5 CH50U/g protein. The assay has a coefficient of variation of 20.4%. PMID- 8360500 TI - Purification of murine Kupffer cells by centrifugal elutriation. AB - Procedures to reproducibly obtain pure preparations of murine Kupffer cells are described. Pure Kupffer cell preparations obtained following collagenase digestion, metrizamide separation and centrifugal elutriation remained viable and maintained their phagocytic functions for at least 4-5 days in vitro. Furthermore, we determined the feasibility of extracting RNA from Kupffer cells obtained immediately following elutriation and after 2 and 4 days of culture in vitro. These RNA extracts were used to determine the level of cytokine gene expression in Kupffer cells. PMID- 8360501 TI - Problems and pitfalls with measurement of antibody affinity using solid phase binding in the ELISA. AB - Current methods of estimation of antibody affinity constants using ELISA assume homogeneous binding of antibody to the solid phase, despite many reports in the literature that this is not true. I have derived theoretical antibody binding curves for solid phase antigen assuming homogeneous antibody binding. I have compared these curves with a set of experimental binding curves of monoclonal antibodies to the serum protein fibronectin. The results conclusively show that while some monoclonal antibodies behave as predicted by theory, others show departures from homogeneous binding which can be explained by various surface effects. I have discussed how these surface effects can cause errors in estimates of either liquid phase or solid phase affinities using the ELISA, and have demonstrated the limitations of methods of affinity ranking. PMID- 8360503 TI - Enzyme release assay of human NK cell activity using beta-galactosidase expressing K562 target cell line. AB - In the present report, we established a K562 cell line useful for an enzyme release assay of human natural killer (NK) activity. Human myelogenous leukemia cell line, K562, was transfected with a plasmid carrying Escherichia coli beta galactosidase (beta-gal) gene. A colony that permanently expresses the enzyme activity was isolated, and designated K562/Zneo. Incubation of K562/Zneo cells (1 x 10(4)) with nonadherent human peripheral blood lymphocytes (PBL) resulted in the release of beta-gal activity depending on the incubation time and the number of effector cells. Released beta-gal activity was assayed sensitively by using 4 methylumbelliferyl-beta-D-galactoside, a fluorescent substrate. The cytolytic activity of PBL was augmented significantly when the cells were preincubated with interleukin-2 for 20 h. This enzyme release assay showed a comparable sensitivity to that of 51Cr release assay. Thus, K562/Zneo cell line is thought to be useful for the nonradioactive assay of human NK and lymphokine-activated killer activities. PMID- 8360502 TI - A modified enzyme-linked immunosorbent assay for measuring type-specific anti pneumococcal capsular polysaccharide antibodies. AB - We have developed an ELISA for antibody determination, superior to others hitherto described, in which optimal coating is achieved using phenylated pneumococcal capsular polysaccharides as coating antigen. The specificity of the assay is ensured by complete inhibition of antibodies against the species specific pneumococcal antigen, C-polysaccharide (C-Ps). The method is sensitive, specific, reproducible, fast and easy to work with and can be used for both immunoglobulin class and subclass antibody determinations. PMID- 8360504 TI - Flow cytometric analysis of cellular DNA content. An alternative approach for the identification and quantitation of xenogeneic cells engrafted in SCID mice. PMID- 8360505 TI - On the purification of IgG from egg yolk. PMID- 8360506 TI - A new method for determining anti-B cell antibodies and their specificity using flow cytometry. AB - We describe a new flow cytometric B cell crossmatch method with improved sensitivity and specificity. It is based on the coating of B cell surface immunoglobulins with an unconjugated polyvalent anti-human immunoglobulin antibody. The method also provides a means for determining the specificity of anti-B cell antibodies and, potentially, for anti-HLA class II antibody specificity differentiation (DR, DQ or DP) in a binding inhibition test using mouse monoclonal antibodies directed against human HLA class II antigens. PMID- 8360507 TI - Direct double antibody sandwich immunoassay for Pseudomonas aeruginosa elastase. AB - A direct sandwich enzyme immunoassay was developed in order to quantify Pseudomonas aeruginosa elastase. As a solid phase the wells of a microtitre plate were coated with specific IgG and horseradish peroxidase labelled IgG was used as the second antibody. The detection limit of the assay was 0.26 ng/ml and a good agreement was found with elastolytic activity determined using elastin-Congo red. This assay was simple, specific, sensitive and reproducible, and permits the determination of low levels of elastase. PMID- 8360508 TI - Purification of antibodies using protein L-binding framework structures in the light chain variable domain. AB - Protein L from the bacterial species Peptostreptococcus magnus binds specifically to the variable domain of Ig light chains, without interfering with the antigen binding site. In this work a genetically engineered fragment of protein L, including four of the repeated Ig-binding repeat units, was employed for the purification of Ig from various sources. Thus, IgG, IgM, and IgA were purified from human and mouse serum in a single step using protein L-Sepharose affinity chromatography. Moreover, human and mouse monoclonal IgG, IgM, and IgA, and human IgG Fab fragments, as well as a mouse/human chimeric recombinant antibody, could be purified from cultures of hybridoma cells or antibody-producing bacterial cells, with protein L-Sepharose. This was also the case with a humanized mouse antibody, in which mouse hypervariable antigen-binding regions had been introduced into a protein L-binding kappa subtype III human IgG. These experiments demonstrate that it is possible to engineer antibodies and antibody fragments (Fab, Fv) with protein L-binding framework regions, which can then be utilized in a protein L-based purification protocol. PMID- 8360509 TI - A novel, sensitive bioassay for transforming growth factor beta. AB - We have developed a simple, sensitive bioassay for transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) based on the ability of these cytokines to inhibit the interleukin-5 induced proliferation of the erythroleukaemia cell line, TF-1. This assay is rapid, reproducible and sensitive to less than 500 fg/ml of TGF-beta 1, and 5-10 pg/ml TGF-beta 2. The assay is 100 1000-fold less sensitive to other inhibitory molecules such as interferon-beta, interferon-gamma and TNF-alpha. The assay can be made specific for TGF-beta 1 or TGF-beta 2 by including specific neutralising antibodies for TGF-beta 1 or TGF beta 2. The assay can recognise all the readily available recombinant molecular species of these molecules as well as the natural proteins produced from human and bovine platelets and detects TGF-beta in serum samples. PMID- 8360510 TI - 51Cr-labeled human hepatocytes as target cells for cytotoxicity mediated by freshly isolated liver-infiltrating lymphocytes. AB - Previous studies on lymphocyte cytotoxicity against autologous human hepatocytes had been studied using Terasaki plates, in which dead hepatocytes after incubation with lymphocytes were counted visually. No studies with 51Cr-labeled human hepatocytes as targets have been reported, although it can give us more objective results. In the present study, we established procedures for labeling human hepatocytes with 51Cr and for measuring cytotoxicity of freshly isolated liver-infiltrating lymphocytes (LIL) against 51Cr-labeled human autologous hepatocytes. Hepatocytes were isolated from diseased and 'normal' liver tissues, cultured overnight, and labeled with 51Cr 'in situ' in the wells of 96-well round bottom plates. Human hepatocytes isolated from either 'normal' or diseased liver tissues labeled well with 51Cr, and mean spontaneous 51Cr release was less than 15% in the presence of 5% fetal bovine serum or human AB serum. Freshly isolated LIL obtained from chronic viral hepatitis but not from other liver diseases showed cytotoxicity against 51Cr-labeled autologous hepatocytes in 4 h 51Cr release assays, and the percent specific lysis was linearly related to the E:T cell ratio. LIL from viral hepatitis were able to mediate natural killer (NK) activity against K562 targets, lymphokine-activated killer-like activity against Daudi cells, and lectin-dependent cellular cytotoxicity. Two-color flow cytometry analysis showed that these LIL contained both CD3+ T cells and CD3-CD56+ NK cells. This is the first report which examined the cytotoxicity of liver infiltrating lymphocytes against 51Cr-labeled human hepatocytes, and it will be useful in assessing local immune response against autologous hepatocytes in chronic liver diseases. PMID- 8360511 TI - Application of the ILISPOT-IDIP system for the enumeration of different sizes of IgA spot forming cells in the murine small and large intestine. AB - The immunofluorescence-linked immunospot (ILISPOT) assay associated with the immunofluorescence digital image processing (IDIP) system was originally developed in our laboratory to allow enumeration of immunoglobulin (Ig) producing, spot forming cells (SFC) in a more objective and quantitative manner. In this study, the ILISPOT-IDIP system was further advanced in order to analyze different sizes of SFC (e.g., IgA producing cells) including large (L), medium (M), and small (S) cells which correspond to high (> 2.4 pg), medium (1.2-2.4 pg) and low (< 1.2 pg) IgA secreting cells by the adaptation of real time image processor and intensified video camera system. When the ILISPOT-IDIP system was used to characterize the frequency of IgA secreting cells among mononuclear cells isolated from different parts of the murine gastrointestinal (GI) tract including the small (upper, middle and lower sections) and large (colon and rectum) intestine, the small intestine contained higher numbers of IgA SFC (approximately 8.4 x 10(5) SFC/10(6) cells) when compared with large intestine (approximately 1.3 x 10(5) SFC/10(6) cells). Among the 3 areas of small intestine, the upper (approximately 3.7 x 10(5) SFC/10(6) cells) and middle (approximately 2.4 x 10(5) SFC/10(6) cells) parts had higher numbers of IgA SFC when compared to the lower small (approximately 2.3 x 10(5) SFC/10(6) cells) intestine. When these IgA producing cells in different parts of the intestine were classified into three groups according to the size of individual spots, the upper and middle intestine contained higher frequencies of large (approximately 20%) and medium (approximately 20%) SFC which corresponded to high and medium IgA secretors in comparison to the lower small (approximately 9%) and large (approximately 6%) intestine. In contrast, the lower small and large intestine were dominated by small SFC since approximately 85% of IgA producing cells were categorized as low secretors. Using the advanced ILISPOT-IDIP system, a unique distribution of different sizes (or secretion rates) of IgA producing SFC was elucidated in the different regions of the mouse small and large intestine. PMID- 8360512 TI - Specificity and sensitivity of polymerase chain reaction (PCR) in comparison with other methods for the detection of mycoplasma contamination in cell lines. AB - The polymerase chain reaction (PCR) amplification was used for the detection of mycoplasma contamination in 42 continuous cell lines. Using the microbiological cultivation on agar as the reference method, 29 cell lines were regarded as positive and 13 cell lines as negative. The double-step PCR analysis employed nested primers that anneal to gene sequences coding for the evolutionarily conserved 16 S rRNA of some 25 different mycoplasma species (including the ones most commonly found in cell cultures). In terms of the positivity or negativity of mycoplasma infection the results were identical for the agar assay and PCR amplification. All positive cell lines displayed distinct, unequivocal, objectively discernible bands on agarose gels while the non-infected specimens showed no DNA amplification. A simultaneously performed comparison with four other commonly used detection methods (DNA-RNA hybridization in solution, DAPI DNA fluorescence staining, immunostaining with a monoclonal antibody and an ELISA) showed that PCR produced significantly less false-negative or false positive results than all the other methods. Furthermore, in dilution experiments, PCR correctly detected the infecting mycoplasmas at the lowest level of 1/10(4) whereas the other assays were less sensitive. It is concluded that double-step PCR employing nested primers is superior to other mycoplasma detection methods in many respects: simplicity and speed, high specificity and extreme sensitivity, objectivity and accuracy. PMID- 8360513 TI - The expression of an adhesion-related protein by clam hemocytes. AB - Molluscs have circulating cells in the hemolymph which are both adherent and phagocytic. Mya arenaria, the soft-shell clam, is particularly interesting because it develops a leukemia detected first in the hemolymph and, as the disease progresses, in solid tissue. We have previously described a leukemia specific protein (Miosky et al., 1989) identified by murine monoclonal antibodies generated to pure populations of leukemia cells. In the following work, a monoclonal antibody was generated to normal hemocytes of Mya. The antibody, designated 2A4, was evaluated by ELISA, immunocytochemistry, Western blotting, and flow cytometry. The 2A4 antigen was detected on 87% normal adherent cells. However, 2A4 was lost as leukemia cells proliferated. The mature leukemia cell, which is nonadherent, neither expresses 2A4 nor can 2A4 be detected in the leukemia cell lystate. Western blot analyses reveal that 2A4 reacts with a 130 kDa protein. Our data suggest that p130 may be involved in the regulation of cell adhesion. PMID- 8360514 TI - Use of synthetic peptides to probe functional domains of a Bacillus thuringiensis toxin. AB - Two 10-residue peptides exhibiting sequence homology to CryIA(a) toxin were chemically synthesized. One corresponds to a segment from residues 48-57 (peptide A) and is common to all CryIA toxins and the second corresponds to a segment from residues 348-357 (peptide B) and is specific to the CryIA(a) toxin. Antibodies were raised in rabbits against both peptides. Antipeptide A did not protect either Bombyx mori or Choristoneura fumiferana larvae against CryIA(a) toxin. However, antipeptide B offered significant protection to B. mori and somewhat less protection to C. fumiferana larvae. Neither antiserum interfered with the binding of CryIA(a) toxin to brush border membrane vesicles of either insect. The results suggest that the segment from residues 348-357 in CryIA(a) toxin is important for expression of toxicity in both insects but not for binding. PMID- 8360515 TI - [Detection and identification of HBV DNA and DNA subtypes of HBs-antigen by the use of the polymerase chain reaction and non-radioactive probes]. AB - A technique of nested polymerase chain reaction (PCR) and hybridization with non radioactive probes was developed for the detection and identification of HBV DNA and HBs-subtypes in very small volumes of human sera. Four oligonucleotide primers (20 mer) complementary to DNA sequences in the S region of HBV and probes (18 or 20 mer) conjugated to alkaline phosphatase were used for the present PCR assay. The results of the PCR assay coincide with those of enzyme immunoassay (EIA) in 14 HBe-positive and 59 HBe-negative samples with 98.6% of specificity. The HBV subtypes adr and adw were identified using an 18-mer DNA probe in 30 samples with an accuracy of 100%. Further, the DNA subtypes were clearly demonstrated in 3 samples where HBs-antigen was undetectable. These results indicate that amplification of HBV DNAs by PCR and their detection with non radioactive probes is a reliable tool for diagnosis of HBV infection in clinical laboratories. PMID- 8360517 TI - Capnocytophaga sputigena bacteremia associated with acute leukemia. AB - During a three-year period, Capnocytophaga sputigena bacteremia occurred in three patients with acute leukemia receiving induction therapy on a hematology ward. Oral pathology such as periodontitis or severe mucositis was considered to be the most likely source of bacteremia. All three blood culture isolates were identified as that species by deoxyribonucleic acid (DNA) homology studies. Because of the phenotypical similarity of Capnocytophaga species, it is difficult to differentiate them by conventional bacteriological methods. All three isolates were susceptible to antibiotics active against most anaerobes. However, production of beta-lactamase was found in two isolates, one of which proved resistant to both piperacillin and ceftazidime. Therefore, the empiric use of imipenem or clindamycin may be justified in febrile granulocytopenic patients with cancer who develop significant oral lesions. PMID- 8360516 TI - [In vitro and clinical studies of MRSA infections in compromised hosts]. AB - From January to December 1991, 47 clinical cases in when methicillin-resistant Staphylococcus aureus (MRSA) strains were isolate were investigated at our internal medicine ward. The MRSA infection rate was 57.4% (27/47). The mortality due to MRSA bacteremia was 75.0% (9/12) and that due to MRSA pneumonia was 57.1% (4/7). We think that MRSA infections must be treated by multiple antibiotics. At out institution, most of the patients were given a combination therapy of imipenem + fosfomycin or imipenemt + mynocycline. Although in vitro the MICs of imipenem did not show excellent activity against MRSA strains, in vivo these combination therapy including imipenem showed excellent activity against MRSA infections. We think that this result was due to the additive effect of the two drug combination. We determined the MICs of single antibiotics against MRSA strains. Most of the MRSA strains were sensitive to minocycline and arbekacin. All MRSA strains were sensitive to vancomycin we think that vancomycin is a highly useful drug to combat MRSA infection. PMID- 8360518 TI - [Effect of the passage and storage of strains, and inoculum size on the change of zone pattern types and sizes produced by protease of methicillin resistant Staphylococcus aureus]. AB - Protease produced by Staphylococcus aureus precipitates digests of casein in standard methods caseinate agar (SMCA) plate, and the various sizes of A to E precipitation types were produced depending on strains of inoculated Staphylococcus aureus, as previously reported. To evaluate these phenomena for epidemiological use, we investigated the effects of bacterial passage, storage and dosage on zonal pattern and the size of precipitation rings. Methicillin resistant Staphylococcus aureus (MRSA) was found to produce variable types and sizes of precipitation rings depending upon the inoculated strains. After 5, 30 and 50 passages in heart infusion broth (HIB), each of the strains randomly selected from MRSA strains showed that the precipitation pattern of A to E produced the same types and sizes of precipitation rings. The storage effects were assessed by comparing those strains in different storage time. The strain stored for 1 and 3 years at room temperature in HIB contained 0.8% agar produced the same pattern of precipitation rings at that of the freshly isolated one. Finally, the dosage of inoculated bacteria was examined. Overnight broth (HIB) cultures of MRSA were directly inoculated in SMCA plates, and were found to produce almost the same size of precipitation rings (reproducible within 3 mm). These findings indicated that protease digestion on SMCA plate provides a rapid, sensitive, and specific assay that can supplement the currently available modalities for typing of MRSA strains. PMID- 8360519 TI - [Etiology of pediatric inpatients with pneumonia]. AB - The etiology of acute pneumonia was studied in 596 pediatric inpatients at Chiba Municipal Kaihin Hospital between January 1990 and December 1991. A pathogen was identified in 389 (64.4%) episodes of pneumonia. Evidence of bacterial infection was present in 167 (28.8%) episodes, viral infection in 178 (29.9%) and Mycoplasma pneumoniae infection in 89 (14.9%). The major bacterial pathogens were H. influenzae 117 (19.6%), S. pneumoniae 51 (8.6%), M (B). catarrhalis 24 (4.0%). RS virus was the most common respiratory virus. The peak age of the patients was 7 months to 2 years old. For bacterial pneumonia, the highest rates occurred in infants. Mycoplasma pneumonia produced the highest rates in school-age children. Mycoplasma pneumonia was prevalent at two distinct times, the first emerging in the spring of 1990 and emerging again in the autumn of 1991. RS virus and influenza virus epidemics occur during the winter. Most of the parainfluenza virus have been observed during the early summer season. PMID- 8360520 TI - Bacterial flora detected of the uterine endometrial cavity of diabetic patients with myoma uteri. AB - Patients with diabetes frequently suffer from various postoperative complications, especially infection. Diabetic patients also have a high incidence of uterine endometrial cancer. The nature of the intrauterine bacterial flora may be related to both infection and carcinogenesis. Therefore, identification of the intrauterine bacterial flora in diabetic patients may be useful. Bacteria were detected in the uterine endometrial cavity of 100% of ten diabetic patients with myoma uteri. However, among 20 non-diabetic control patients with myoma uteri, only three 15% harbored bacteria. Members of the Enterobacteriaceae (Escherichia coli, Proteus spp., Enterobacter cloacae, and Klebsiella pneumoniae) were the predominant bacteria. We speculate that bacterial products contribute to carcinogenesis, as has been proposed for colon carcinoma. Antimicrobial agents active against Enterobacteriaceae should be used to prevent postoperative infections in gynecologic procedures in diabetic patients. PMID- 8360521 TI - Macrophages in the urine in acute bacterial cystitis. AB - In the previous study in this series of studies concerning the role of macrophages in urinary tract infection, we attempted to detect macrophages in the urine of acute bacterial cystitis patients by nonspecific esterase staining of urinary sediment, however none of the leukocytes stained, probably because of cell damage caused by the urine and by centrifugation. In the present study, detection of macrophages in urine was again attempted, this time by prompt transfer of urinary leukocytes to culture medium after minimum centrifugation, 1 hr culture in a glass bottom chamber and non-specific staining of leukocytes adhering to glass. Macrophages in urine were detected by this method, and they comprised 5.9% of the adherent leukocytes, although macrophage spreading, which implies macrophage activation and is often seen in the early stage of nonbacterial prostatitis, was hardly ever observed. The percentages of adherent leukocytes were not correlated with urine osmolarity, probably because the effect of urine was minimized by prompt transfer of urinary leukocytes to culture medium after the urine samples had been collected. There have been quite few studies involving culture of urinary leukocytes in the past. Our simple techniques, such as prompt transfer of urinary leukocytes to culture medium after centrifuging with minimum gravity and for a minimum period of time, appear to be useful in the study of urinary leukocytes using other cells which appear in urinary tract infection, as well as cytokines and antibiotics, to clarify cellular mechanisms of defenses in urinary tract infection. PMID- 8360522 TI - [Study of bacterial flora in the stomach and the upper and lower respiratory tracts--the mechanism of lower respiratory tract infection]. AB - To evaluate the mechanism of lower respiratory tract infection in the hospital, gastric juice, throat secretions, secretions in tracheal cannulae or tubes and aspirated sputum were cultured simultaneously in seven patients with tracheostomy and seven patients with tracheal intubation. Thirty-six strains of bacteria were isolated from gastric juice and only 22.2% of them were the same bacteria as those in the throat secretions. This suggested that there was little correlation between gastric and oropharyngeal flora. The bacteria isolated from throat secretions and aspirated sputum showed 38.5% coincidence in tracheostomized patients and 80% coincidence in intubated patients. In addition, the rate of agreement was 33.3% in tracheostomized patients and 88.9% in intubated patients between throat secretions and tracheal cannulae or tubes. These findings suggested that the correlation of bacterial flora between the upper and lower respiratory tracts was high in intubated patients and low in tracheostomized patients. Identical bacteria in the stomach and the upper and lower respiratory tracts (which may cause nosocomial infection) were isolated in only four of the 14 patients. It has been suggested that bacterial flora in the lower respiratory tract are transmitted from the stomach to the oropharynx and then cause lower respiratory tract infection in hospital. However, our study suggested that this was not a common pathogenic mechanism. PMID- 8360523 TI - [Clinical study of patients with deep-seated fungal infection associated with hematological diseases]. AB - An assessment has been made regarding usefulness of measuring beta-D-glucan (beta glucan) as fungal serodiagnosis in 50 cases of fungal infection with hematological diseases. Further, an assessment has been made regarding relation between hematological findings and therapeutic effect by administering miconazole, an antifungal agent (MCZ: Florid, clinically to the subjects. Positivity of beta-glucan (beta-glucan > or = 10 pg/ml) was observed in 54.5% (24/44), and the effective rate of MCZ in the positive cases was 75.0% (18/24). In the cases in whom fungus was detected, beta-glucan-positive rate was 50.0% (8/16), and MCZ-effective rate in beta-glucan-positive cases was 62.5% (5/8). The total effective rate of MCZ was 80% (40/50). Side effects were observed in 3 cases, but continual administration of MCZ was possible in all of the 3 cases. By the assessment regarding the relation between hematological findings and therapeutic effect of MCZ, it was found that the effective rates in the cases who underwent a transition with neutrophil and lymphocyte counts less than 500/microliters during the period of MCZ administration were 64.7% (11/17) and 50% (5/10), respectively, and large effects were observed in the cases who underwent a transition with the neutrophil and lymphocyte counts more than 500/microliters was 86.7% (19/22) and 91.7% (22/24), respectively. These results suggested that lymphocytes rather than neutrophils had an important role in the morbidity of fungal infection. It was noteworthy that MCZ was effective for the treatment of deep seated mycosis and significant effective rate was obtained in the group of patients who had neutrophils and lymphocytes less than 500/microliters. PMID- 8360524 TI - [A case of brain abscess due to Streptococcus sanguis in association with multiple pulmonary arteriovenous fistulas]. AB - A case is reported here of brain abscess due to Streptococcus sanguis in association with multiple pulmonary arteriovenous fistulas. A 19-year-old male who had been diagnosed in 1988 as pulmonary arteriovenous fistulas was admitted to our hospital for repeated epistaxis, headache, and vomiting. A brain abscess which was diagnosed using various roentogenologic examinations, worsened despite conservative therapy. Additional surgical drainage was performed; S. sanguis was isolated from the drainage fluid. After drainage, clinical symptoms gradually improved with no subsequent neurological deficits. We have formulated the following hypothesis regarding the mechanism of abscess formation in this case: S. sanguis invaded from a ruptured nasomucosal vein, forming a septic emboli in the blood flow, which passed through a pulmonary arteriovenous shunt and led to the formation of a brain abscess which established a metastatic presence in the cerebral tissue. PMID- 8360525 TI - [Assessment of left ventricular contraction with LV Emax during cardiopulmonary bypass in patients with open heart surgery]. AB - There are few reports on the assessment of left ventricular contraction during cardiopulmonary bypass (CPB) in open heart surgery. LV Emax is thought to be a load-independent index of left ventricular function. We used a left ventricular conductance catheter to measure LV Emax from "non-working beating heart" during CPB in 16 patients who underwent open heart surgery. During CPB, at 45 minutes after aortic declamping, changes of heart rate with atrial pacing (120/min) did not change LV Emax, but after intravenous dobutamine administration (DOB, 10 micrograms/kg/min) LV Emax increased by 26% (p < 0.01). DOB increased LV Emax in 14 of 16 patients during CPB. These 14 patients were weaned from CPB without difficulty. But in 2 other patients DOB didn't increase LV Emax during CPB. In order to be weaned from CPB, the two patients needed epinephrine and intraaortic balloon pumping. We concluded that change of LV Emax made by intravenous administration of dobutamine is one of useful indexes to assess left ventricular contractility during cardiopulmonary bypass. PMID- 8360527 TI - [Local resection of pulmonary lesions by Nd-YAG laser without suturing]. AB - Local excision of 67 pulmonary lesions in 5 patients was performed with the Nd YAG laser. There were 2 women and 3 men with an average age of 68 years. The patients consisted of three cases of metastatic lung cancer (65 lesions), one hamartoma (One lesion) and one organized pneumonitis (one lesion). The lesion was first enucleated by a contact method using an Nd-YAG laser scalpel, then the crater of the resected lesion in the normal lung tissue was coagulated with a defocused laser beam. The craters of 52 of the 67 resected lesions which were shallow seated in the lung were left open, but the other 15 resected lesions were closed with sutures. Total blood loss was less than 100 ml. There was no bleeding or air leakage (30 cm water pressure) during the post operative days in 4 of the 5 patients, but one patients (one lesion) had to be treated by bronchoscopic endobronchial embolization against a persistent air leak. This lesion was 2.5 cm in diameter and 4 cm deep in the lung on CT. The other lesions were also measured by CT. The tumor size was 1.4 +/- 0.7 cm and the depth was 2.4 +/- 1.0 cm. The Nd YAG laser is very suitable for local resection of peripheral lung lesions without suturing. PMID- 8360526 TI - [Risk factors and therapeutic methods for sternal wound infection following cardiac surgery]. AB - In a study of 1040 patients undergoing cardiac surgery at The Osaka Medical College Hospital from 1984 through 1991, we analyzed the correlation between a variety of preoperative and operative parameters and the risk of postoperative sternal wound infection, as well as the efficacy of various therapeutic method for this condition. Sternal infection or mediastinitis developed after cardiac surgery in 31 patients (3.0%). As the risk factors for wound infections, age, diabetes mellitus, reexploration, duration of cardiopulmonary bypass and use of bilateral internal thoracic artery grafting were listed. Application of pectoral muscle flaps significantly led to shorten a duration between diagnosis of infection and hospital discharge, and increased survival rate, than the other treating methods such as debridement or irrigation. We conclude that bilateral internal thoracic artery grafts should not be used in the cases with diabetes, and closure with pectoral muscle flaps is effective for sternal infection and mediastinitis. PMID- 8360528 TI - [Pathological assessments of allografts after heart transplantation using a dog model--allograft vasculopathy]. AB - The pathological findings of allografts after heart transplantation were assessed in long-term period using a dog model. Eight orthotopic heart transplantations were performed with cross-circulation method using a dog. Two dogs survived over 1 year after heart transplantation. One dog died due to cardiac rejection, and the another dog died due to infection at 14 months and 16 months after the transplantation, respectively. The coronary artery morphologic features were assessed in the allografts. The pathological findings showed fibrous intimal thickening with infiltration of lymphocytes and macrophages. And it was diffusely distributed to each area of transplanted heart. The stenosis of coronary lumen was significantly seen in middle size of coronary arteries which was from 100 microns to 50 microns. The characteristics of these findings in comparison with arteriosclerosis change were 1) rapid progression, 2) diffuse fibrous intimal thickening, 3) preserved internal elastic lamia. These findings might be important for treating this complication. PMID- 8360529 TI - [Late results and problems after atrial switch operation]. AB - Between 1970 and June 1992, 137 consecutive patients with transposition of the great arteries and double outlet right ventricle underwent an atrial switch operation at the Heart Institute of Japan. They included 74 patients with a Senning operation (Group I) and 63 patients with a Mustard operation (Group II). Ages at operation ranged from 1 month to 15 years (average 25.7 months) and follow-up period in 114 operative survivors ranged from 1 month to 22 years (average 6.8 years in the Senning group, 10.9 years in the Mustard group). Twelve year actuarial survival rate was 90.1% in Group I and 64.1% in Group II, and 22 year actuarial survival rate was 64.1% in Group II. There were 6 and 13 late deaths in group I and group II, respectively. Sudden Death occurred in 7 patients in the late postoperative period presumably due to arrhythmias, although there were no symptoms and signs of arrhythmias in 4 of the 7 patients. Five other patients died from cardiac failure in the late postoperative period. Ninety-two percent of group I and seventy-one percent of group II maintained normal sinus rhythm evaluated by the electrocardiogram and Holter's electrocardiogram in the late postoperative period. Mean PQ interval in the late postoperative period was 0.14 +/- 0.03 seconds in group I and 0.17 +/- 0.03 seconds in group II; Group II had a higher incidence of arrhythmias than group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360530 TI - [Pathologic changes at the coronary artery-bypass graft anastomosis--an immunocytochemical study]. AB - We have performed immunocytochemical investigations on proliferative tissues observed in anastomotic sites of the saphenous vein aortocoronary bypass grafts to the coronary arteries. Nine anastomotic sites were obtained from 5 necropsy patients who had died after bypass grafting. Interval between the operation and death in these patients varied from 5 days to 9 months. The anastomotic sites were fixed in methanol-Carnoy's fixative, and embedded in paraffin. Six monoclonal antibodies specific for muscle cell actin (HHF35), smooth muscle cell actin (CGA7), vimentin, desmin, macrophages (HAM56) and endothelial cells were used for the immunocytochemical study. Of the 9 anastomotic sites, 4 were totally occluded, while the remaining 5 were patent. The occluded sites were characterized by a presence of fresh or organized thrombus. Immunocytochemically, the latter was composed of macrophages, smooth muscle cells and neovascularization. In contrast, a patent site at 5 days after grafting showed an early stage of intimal proliferation composed of macrophages and spindle-shaped cells. Two patent sites at 33 days after grafting revealed a distinct intimal thickening consisting almost entirely of smooth muscle cells. At this stage, smooth muscle cells at a deeper intima were stained positive with both HHF35 and CGA7, whereas the cells at the luminal site were stained positive with HHF35 but negative with CGA7. In older lesion at 9 months after grafting, almost all smooth muscle cells within intimal thickening showed positive with HHF35 and CGA7. Moreover, these smooth muscle cells were stained positive with vimentin but were negative with desmin, irrespective of the lesion's age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360531 TI - [Peritoneal dialysis following open heart surgery in children]. AB - From 1982 to 1991, 13 (3.9%) of 336 children who underwent open heart surgery required peritoneal dialysis postoperatively, including 5 with transposition of the great arteries, 4 with tetralogy of Fallot, 2 with ventricular septal defect, 1 each with atrioventricular canal defects and total anomalous pulmonary venous connection. Patients ages ranged from 12 days to 4 years (mean, 1 year and 4 months). The infusion catheter was directed toward diaphragm from the right lower quadrant, and the drainage catheter was placed in the pelvis from the left upper quadrant. Dialysis solution was instilled and drained simultaneously. Seven children (54%) recovered renal function, with six (46%) longterm survivors. Differences between patients who did and did not recovered renal function (Group A and Group B respectively) were examined. No significant intergroup difference existed in age or weight. PD was initiated significantly sooner in Group B (1.2 +/- 0.8 days) than in Group A (3.2 +/- 1.9 days) (p < 0.05). The negative fluid balance was 88.0 +/- 31 mL/kg/day in Group A and 78.4 +/- 25.0 mL/kd/day (NS). BUN and serum creatinine concentrations were slightly elevated in both group, but were not significant different. Patients in Group A were dialyzed from 3 days to 21 days (mean 9.9 +/- 6.4 days), and patients in Group B were dialyzed from 1 day to 14 days (mean 5.3 +/- 5.2 days) (NS). The central venous pressure (CVP) in Group A decreased while blood pressure (BP) and renal perfusion pressure (RPP) increased following initiation of PD. CVP increased in Group B, while BP and RPP decreased. All patients died of low cardiac output syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360532 TI - [Effectiveness of continuous retrograde cerebral perfusion for surgical treatment of aneurysms of the aortic arch--comparison with antegrade cerebral perfusion]. AB - Several methods have been used for an adjunct to perform operation of aortic arch aneurysms. However, their results were often not so reasonable. Recently retrograde cerebral perfusion was reported as a new adjunctive method. In our institute, for the past 6 and a half years from May 1985 to April 1992, 50 patients underwent reconstruction of the transverse aortic arch by using two methods of artificial cerebral perfusion. One method is continuous antegrade cerebral perfusion (ACP, for 32 patients), and the other is continuous retrograde cerebral perfusion (RCP, for 18 patients), each technique was combined with deep hypothermia (18-20 degrees C) and low flow perfusion (10-30 ml/kg/min) to lower half body performed from femoral artery. In our RCP circuit, an additional pump was used for cerebral perfusion to superior vena cava, but the circuit was much simpler than the circuit in ACP. We compared the two methods (ACP versus RCP) as regards to the following items and the results were showed in parentheses; hospital death (8/32, 25%: 2/18, 11%), respiratory complication (8.27, 30%: 3/18, 17%), neurological complication (7/29, 24%: 1/18, 5.5%), duration of extracorporeal circulation (306.8 +/- 74.5 min: 260.4 +/- 60.0 min), periods of pre-ECC in the operation (160.3 +/- 69.2 min: 117.7 +/- 35.3 min), duration of cerebral perfusion (113.6 +/- 45.4 min: 74.1 30.5 min) and amount of bleeding (3424 +/- 2881 ml: 1802 +/- 1291 ml). RCP has superior advantages in all of those in comparison with ACP. These results suggest that RCP is a useful adjunctive method for reconstruction of aortic arch with a low operative risk. PMID- 8360533 TI - [Aortic valve replacement for narrow aortic ostium, supraannular insertion at noncoronary sinus with Bjrk-Shiley valve]. AB - Fifteen patients with small aortic annuli underwent aortic valve replacement either isolated or combined with other procedures. All patients had aortic valve replacement with Bjork-Shiley prosthesis larger than the aortic annulus. The prosthesis was sutured in a supraannular position in the area corresponding to the noncoronary sinus. There was no hospital and late death. In the long term follow up, 21 mm prosthetic gradients by doppler method ranged from 17 to 43 (29.9 +/- 7.3) mmHg in patients with supraannular aortic valve replacement and from 20 to 45 (27.4 +/- 7.1) mmHg in patients with standard aortic valve replacement, which showed statistically no significant difference. Because this technique allows the insertion of prosthetic valves one sizes larger than the size of aortic annulus, it will produce stable hemodynamic result. As a consequence, those procedure such as transannular patch reconstruction will be avoided. PMID- 8360534 TI - [Cell viability assessment of cold-preserved (4 degrees C) and cryopreserved ( 196 degrees C) allograft valves by flowcytometric analysis]. AB - We introduced cryopreservation technique to store the allograft valve and subsequently commenced the use of the cryopreserved aortic allograft valve for aortic valve replacement. For the clinical use of the allograft valve, it is essential to evaluate the cell viability. We assessed cell viability of the allograft valve by flowcytometry (FCM), using a fluorescein diacetate (FDA) propidium iodide (PI) stain. Pulmonary allograft valves were harvested from the cadavers with a consent. Of the 9 valves collected and sterilized in 4 degrees C antibiotic solution for 48 hours, 4 valves were stored under refrigeration (cold preserved), and the remaining 5 valves were cryopreserved. The warm ischemic time from cardiac death to valve preservation was 7.3 +/- 5.4 hours. The cold preserved valves were stored at 4 degrees C in the nutrient medium (TC-199, calf serum and HEPES buffer). The cryopreserved valves were frozen by a programmable freezer to -80 degrees C in the same nutrient medium containing 10% dimethylsulfoxide (DMSO), and subsequently stored in liquid nitrogen (-196 degrees C). We assessed the cell viability of the allograft valve leaflet, before storage and at 2 weeks, 1 month and 2 months after the storage. Suspensions of the valve leaflet fibroblasts were double-stained with FDA (1 micrograms/ml) and PI (1 microgram/ml) for flowcytometric analysis of the viable cells (cells showing a chromatic response to FDA but no response to PI). In the cold-preserved group, percentage of the viable cell was 90.3 +/- 3.6% before storage, 62.0 +/- 3.0% after 1 month of storage, and 50.3 +/- 3.7% after 2 months of storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360536 TI - [Study on prevention of paraplegia during occlusion blockade of the thoracic aorta--examination of the evoked potential in the motor nerve induced by stimulation of the motor area of cerebral cortex]. AB - In an attempt to trace the motor neurons in the descending tract of the motor system of the spinal cord and anterior horn, we have succeeded in inducing a potential in the peripheral motor nerve (evoked motor nerve action potential: EMNAP) by stimulating the motor area of the cerebral cortex in dogs, we have examined the characteristics of this potential. Besides the EMNAP, we have induced the conventional somatosensory evoked potential (SSEP) and evoked spinal cord potential (ESCP) during spinal ischemia. These are compared with each other, with theoretical predictions and with pathological findings. EMNAP possessed a biphasic negative potential (N1, N2) and subsequent multiphasic potential (N3+n) during the latency 10-18 msec. The stimulation threshold of EMNAP in the lower limbs was the lowest near the longitudinal fissure in the anterior part of the cerebral crucial groove. The amplitude of N2 and N3+n of EMNAP decreased under the condition of frequent stimulation. N2 and N3+n did not disappear after the dorsal root was severed. When the three potentials of EMNAP, SSEP, and ESCP were simultaneously induced, the left subclavian artery was occluded, the descending aorta was partially occluded immediately under the bifurcation of this artery, and the pressure of the partially occluded periphery was gradually reduced, EMNAP alone disappeared at 45.2 +/- 6.2 mmHg. Although ESCP and SSEP did not disappear even when partial occluding was continued for 90 minutes under this condition, histopathological findings obtained by formalin perfusion fixation showed ischemic disorder of the anterior horn cells when compared with the normal group fixed in the same way. EMNAP was considered to be induced through the alpha motoneuron in the anterior horn of the spinal cord, and disappeared under the critical ischemia in which ESCP and SSEP do not disappear. Disorder of the anterior horn cells were also observed histopathologically. Direct monitoring of the alpha-motoneuron in the anterior horn, which is most susceptible to disorders, seems appropriate as a method for preventing paraplegia. EMNAP may be useful for monitoring motor function of the spinal cord not only during chest surgery but also for other types of diagnosis and treatment. PMID- 8360535 TI - [Surgical treatment of type A aortic dissection combined with aortic root lesions]. AB - From January 1980 to December 1992, 36 patients with type A aortic dissection were operated on at the St. Marianna University Hospital. Hospital mortality and 10-year survival rate in 26 patients (Group I and II) undergoing replacement of the ascending aorta with or without hemi-arch resection (including one case of aortic wrapping for the closing dissection) were 19.2% and 88.0%, respectively. Among the patients having aortic root destructions due to acute aortic dissection or preexisting annuloaortic ectasia (Group III), 8 patients underwent aortic root reconstruction with a valved conduit and 2 patients supra-coronary aortic resection and graft replacement with concomitant coronary artery bypass grafting with 20.0% of hospital mortality and 55.6% of 10-year cumulative survival rate. Modified Bentall operation using Carrel patch method seems to be preferable to avoid postoperative complications for the case with intimal tear extending to the aortic sinuses, ruptured outer layer of the aortic root or preexisting AAE. If the disrupted coronary artery is concerned, coronary artery bypass grafting is mandatory. In the case of replacement of the ascending aorta for the dissection extending to the aortic sinuses, complete obliteration of the proximal false lumen must be required to avoid uncontrollable bleeding and compromised coronary blood flow. PMID- 8360537 TI - [Quantitative assessment of fibroblast viability in cryopreserved aortic valve allografts]. AB - The purpose of this study is to clarify whether serum (fetal bovine serum or human serum) is necessary or not for cryopreservation of aortic valve allografts. The protective effects of fetal bovine serum compared with human serum were evaluated by means of quantitative assessment of fibroblast viability. Porcine aortic valves were excised and rinsed immediately after death, followed by treatment with low concentration antibiotics. Valves were gradually frozen at a control-rate of -1 degree C/min and then stored in liquid nitrogen vapor-phase. The samples were classified into three groups by nutrient medium as follows. Group A (n = 5); Dulbecco's Modified Eagle Medium (DMEM), Group B (n = 5); DMEM containing 10% fetal bovine serum, Group C (n = 5); DMEM containing 20% human serum. At 1 week, 1 month, and 3 months after initiation of storage, the valves were thawed rapidly and examined for fibroblast viability, which was assessed quantitatively by means of autoradiography with tritiated proline. After 1 week storage, the fibroblast viability rate reduced from 98% to 80.7% in group A, 79.4% in group B and 79.2% in group C respectively, but there were no significant differences among three groups. The viability rate decreased with the passage of time, and remained around 72% in all groups after 3 months storage. The histological examination did not show any changes in the structure of the valves in all samples up to 3 months of storage. The results demonstrate that the fibroblasts are still viable after 3 months storage by cryopreservation. The addition of fetal bovine serum or human serum does not improve fibroblast viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360538 TI - [Experimental study on the hydrodynamic performance of "valved pericardial roll"]. AB - Optimal configuration and hydrodynamic performance of "Valved Pericardial Roll (VPR)" as an external conduit was studied using a mock circulatory system which was able to simulate a right cardiac function of infants. Results were as follows: 1) Cardiac output produced by VPR was consistently higher than that by non valved pericardial roll. This result showed the hemodynamic effectiveness of VPR at early stage of operation. 2) Cardiac output by VPR tended to decreased as an elevation of afterload and/or an increment of pulse rate. This result exhibited that VPR had a comparable performance to the Ionescu-Sihley pericardial valve, a satisfactory performance of which was recognized clinically. 3) The optimal configuration related to the length of valve leaflet (LVL) were obtained from the simulation data. VPR with two leaflets produced the best performance when each LVL was design to be 95% of the roll diameter. Among the VPR with three leaflets, the best LVL was 85%. Thus far, VPR which was developed based on the above fundamental studies, indicated satisfactory performance as compared to the conventional surgical treatment. PMID- 8360540 TI - [A case report of aortic valve and VSD Dacron patch infective endocarditis after VSD patch closure 15 years ago]. AB - A 39-year-old man who had undergone the patch closure of the VSD 15 years ago, was admitted with a diagnosis of infective endocarditis due to Alcaligenes Xylosoxidans. Echocardiography revealed vegetation of the aortic valve and a high echoic lesion on the ventricular septum. Surgical findings showed vegetation of the aortic valve and a subannular type mycotic aneurysm. In the aneurysm, the infected pledget used in a previous surgery was found. After debridement, direct closure of the aneurysm, aortic valve replacement (AVR) using a #25 SJM prosthetic valve, and mitral annuloplasty were performed. Two months later, fever developed. The patient was diagnosed with prosthetic valve endocarditis and a second surgery was performed. The prosthetic valve was clear, but an infected Dacron patch used for VSD closure 15 years earlier was found. Debridement, patch closure of the ventricular septum, and re-AVR were performed. The post-operative course was uneventful. This is thought to be a rare case, because infection extended from the aortic valve to the VSD type II Dacron patch, and remained to the VSD type II Dacron patch. PMID- 8360539 TI - [Efficacy of myocardial preservation using GIK solution for prolonged ischemic heart]. AB - The efficacy of myocardial preservation using GIK solution combined with continuous cold blood perfusion was assessed in patients with prolonged ischemia. Fifteen patients receiving more than 4 hours' ischemia were divided into two groups. In Group A, seven patients were associated with severe aortic regurgitation and showed increased left ventricular volume of more than 60 mm in LVDd and 45 mm in LVDs. In Group B, eight patients had a normal left ventricular volume of less than 60 mm in LVDd and 45 mm in LVDs echocardiographically. There was no significant difference in ischemic time, or preoperative hemodynamic parameters between the two groups. The postoperative cardiac index was 2.93 +/- 0.87 in Group A and 4.3 +/- 0.8 in Group B (p < 0.01). The postoperative shortening fraction was 0.17 +/- 0.01 in Group A, 0.43 +/- 0.12 in Group B (p < 0.01). These parameters significantly deteriorated in Group A compared to Group B. Released enzymes (GOT, CK-MB) were significantly increased in Group A with prolonged ischemic time. In conclusion, postoperative cardiac function after 4 hours' ischemia using GIK solution deteriorated in the patients with a dilated heart due to aortic regurgitation. PMID- 8360541 TI - [Reexpansion pulmonary edema after removal of a huge localized mesothelioma]. AB - A 70-year-old female with hypoglycemia was admitted to our hospital for progressive dyspnea. In chest X-ray film, a mass occupied two thirds of the left hemi-thorax followed by the right shift of the mediastinum. Thoracotomy revealed that a huge tumor grew from the left upper lobe and the diaphragm without invasion. The resected tumor was 2550 g in weight. Histological diagnosis was benign fibrous mesothelioma. A large amount of expectoration started soon after the resection of the tumor. Measurement of protein in tracheal fluid and serum revealed that the event resulted from the reexpansion of the left lung after the huge mass removal. The patient recovered from pulmonary edema followed by steroid administration and respiratory management. We consider that it is useful to measure the protein in tracheal fluid and serum for diagnosis of reexpansion pulmonary edema. PMID- 8360542 TI - [A case of thymoma associated with hypogammaglobulinemia]. AB - In this paper, we report a case of thymoma associated with hypogammaglobulinemia, a relatively rare disorder. The case involved a 79-year-old man, who was told, following the diagnosis of an upper respiratory tract infection, that he had a tumor shadow in the anterior mediastinum. A preoperative examination revealed hypogammaglobulinemia. An extended thymectomy was performed. The tumor that was removed was found to be a noninvasive spindle cell thymoma. After three years of postoperative treatment, no tumor recurrence was observed. The hypogammaglobulinemia, however, did not improve, and the subject suffered from repeated occurrences of pneumonia. PMID- 8360543 TI - [A case of left atrial myxoma with acute myocardial infarction--emergency coronary artery bypass grafting and removal of left atrial myxoma]. AB - A 68-year-old woman had clinical signs of an acute myocardial infarction. Echocardiography revealed a tumor in the left atrium. Coronary angiography demonstrated total occlusion at RCA#1. On emergency operation a left atrial myxoma was removed and aortocoronary saphenous vein graft to the right coronary artery was performed. The operative correction of coronary arterial obstruction due to cardiac myxoma or thrombus is rare. PMID- 8360544 TI - [A case report of redo Fontan operation]. AB - A 21-year-old man, who had undergone Fontan operation for tricuspid atresia type 1b using 21 mm Hancock valved conduit 15 years ago, had right sided heart failure when his heart rhythm turned to atrial fibrillation. On cardiac catheterization, pressure data revealed that trans valved conduit pressure gradient reached to 5.2 mmHg. Chest CT and right atrial angiography showed right atrial wall thrombus. Right upper lobe perfusion defect was detected by lung perfusion scintigraphy. Then he was recommended redo Fontan operation. He underwent resection of stenosed valved conduit, right atrial thrombectomy and reconstruction of new route between right atrium and pulmonary artery with bovine pericardium. He tolerated well that operation and now 3 months passed, he resumed fairly vigorous physical activity. PMID- 8360545 TI - [Acute aortic dissection due to cross-clamp injury during coronary artery bypass grafting--a report of successfully repaired case]. AB - A case with successfully repaired acute aortic dissection due to cross-clamp injury during coronary bypass surgery was reported. A 54-year-old man had usual coronary artery bypass surgery by using 3 saphenous vein grafts (4 distal anastomosis). Immediately after the completion of cardiopulmonary bypass, acute aortic dissection, which was caused by aortic cross-clamp, was noted. Cardiopulmonary bypass was resumed and the injured ascending aorta was replaced with prosthetic graft under profound hypothermia and circulatory arrest. An "Island flap" of the ascending aorta (3 x 4 cm in diameter), containing 3 proximal anastomotic positions of vein grafts, was excised from the aortic wall, and was re-implanted into the frontal wall of the aortic prosthesis. The patient well tolerated the operative procedure, and fully recovered from the serious condition after 6 days of IABP support and 11 days of inotropic support. He is doing quite well one year after the surgery. This case is believed to be the first reported one of such reconstructive method for acute aortic dissection during the coronary bypass surgery. PMID- 8360546 TI - [A case of simultaneous association of an early esophageal carcinoma and an early gastric carcinoma with radical operation]. AB - We encountered a case of simultaneous association of an intraepithelial esophageal carcinoma and an intramucosal gastric carcinoma with radical operation. Up to present, only four cases including this report had been printed in Japan. A 67-year-old with chronic cholecystitis was pointed out the esophageal lesion (O-IIa) in the Im area by FGS after it had demonstrated the gastric lesion (early I) at the posterior wall of the prepyrolus. We performed subtotal esophagectomy, total gastrectomy, pyroloplasty with esophagoileostomy through the retrosternal tunnel and lymph nodes dissection (R2). On gross inspection, there was no obvious lesion in the esophagus. Microscopic examination revealed no invasion of cancerous cells to lymph nodes, lymph ducts, and vessels. The patient followed post operative respiratory disorders which not lung edema but atelectasis caused because perioperative measurement of Extra Vascular Lung Water Index (EVLWI) was stable within normal values. PMID- 8360547 TI - [A case report of the preoperative diagnosis of thoracoabdominal aortic aneurysm by three-dimensional CT angiography]. AB - A sixty-year-old woman with the thoracoabdominal aortic aneurysm (7 cm in the diameter) was evaluated by the newly developed three-dimensional CT angiography. The thoracoabdominal aortic aneurysm was scanned by spiral CT and three dimensional images were generated preoperatively. The three-dimensional structures of the thoracoabdominal aorta with the aneurysm, the celiac trunk and the superior mesenteric artery were clearly visualized by this method. The thoracoabdominal aorta was replaced by the graft with the reconstruction of celiac trunk. The post-operative course was uneventful. The preoperative diagnosis of thoracoabdominal aortic aneurysm by this method was very useful in the determination of operative procedure in this case. Three-dimensional CT angiography may be the useful method in the preoperative diagnosis of the aortic surgery. PMID- 8360548 TI - [A case of treatment of the Paget-Schroetter syndrome with PTA and Gianturco' expandable metallic stent]. AB - We report a effective management of the Paget-Schroetter syndrome. A 23-year-old man was seen with a complaint of arm swelling and venous engorgement of the left arm. A first-rib resection was performed through a infraclavicular approach with removal of compressive elements including scalenus anterior and subclavius muscles. He became asymptomatic. But 2 months later, recurrent symptoms developed and venograms demonstrated the presence of restenosis of the subclavian vein with extensive collaterals. To relieve symptoms a percutaneous transluminal angioplasty (PTA) and a insertion and placement of the Gianturco's expandable metallic stents was carried out for the remaining stenosis of the subclavicular vein and a residual compression. Venograms, 7 months after operation, showed widely the patent subclavian vein. Trans-infraclavicular approach allowed exposure of the stenotic or obstructed segments of the subclavian vein. The PTA and stenting, especially after removal of compressive elements or during chronic phase, was a very useful and effective procedure for the treatment of the Paget Schroetter syndrome. PMID- 8360549 TI - [A case of partial anomalous pulmonary venous connection to the high superior vena cava with intact atrial septum]. AB - A 16-year-old female with partial anomalous pulmonary venous connection to the high superior vena cava underwent a successful correction using only autologous pericardium. Right upper pulmonary venous blood returned to the left atrium via the superior vena cava and the constructed atrial septal defect. The right atrium received blood from the brachiocephalic vein through the conduit. The azygos vein was not identified. Post-operative examination revealed that there were no pressure gradients across the superior vena cava and the conduit. She was discharged from the hospital on the 14th post-operative day. PMID- 8360550 TI - [A successful case of emergency coronary artery bypass grafting for a patient with cardiopulmonary arrest on arrival at our hospital due to acute myocardial infarction]. AB - A successful case of emergency coronary artery bypass grafting for a 62-year-old man with cardiopulmonary arrest due to acute myocardial infarction was reported. He developed cardiopulmonary arrest 4 minutes before arrival at Critical care and Emergency Department of our hospital. The ECG of the patient showed ventricular fibrillation. He was resuscitated successfully 26 minutes after cardiopulmonary arrest. Emergency coronary angiography revealed that LAD just proximal was totally occluded and LCx just proximal was 90% stenosed. As he was still in the state of shock after resuscitation, emergency CABG was performed to LAD and LCx using saphenous vein grafts. The post operative course was uneventful. The patient has resumed a normal and active life-style as a deput principal of a high school one year after operation. PMID- 8360551 TI - [Application of cryopreserved allograft to aortic root replacement for valve detachment case due to aortitis]. AB - A 54-year-old male who had received an aortic valve replacement with SJM 23 about 3 years before suffered from an acute cardiac failure because of the valve detachment. From his clinical course, it was diagnosed that the aortic valve insufficiency was complicated by an aortitis. We operated on him by an aortic root replacement using a cryopreserved allograft which we prepared. A donor of the allograft was 35-year-old male, died of a subarachnoidal hemorrhage. We harvested his aortic root at an autopsy and dipped it into a nutrition medium with 10% dimethylsulfoxide. Within 10 hours from his death, we froze the tissue using a program freezer and stored it in a liquid nitrogen for 7 months. After thawing it in 37 degrees C water quickly, we rinsed the graft and used for the operation. The cell viability of the graft was confirmed by a tissue culture. Indication of the allograft valve to an aortitis case is still controversial. We think the allograft is recommendable to valve detachment case due to aortitis, because the softness of the graft decreases a compliance mismatch between the graft and the patient's annulus, which may prevent redetachment. Although we felt concern about redetachment of the conduit due to the weakness of the patient's aortic annulus, no complication regarding the allograft happened at all as yet. PMID- 8360552 TI - [Solitary fibrous tumor (SFT) of the thymic area--a case report]. AB - A 52-year-old man was referred to our hospital with a large anterior mediastinal tumor on chest X-ray. A preoperative CT scan revealed the large tumor in front of the ascending aorta. We failed aspiration biopsies for several times because of scant tumor cells. This tumor was totally removed with a small part of the pericardium through median sternotomy after preoperative radiation therapy consisting of a total dose of 25 Gy. There was no metastasis to regional lymph nodes nor dissemination in the anterior mediastinum. The tumor was encapsulated, 9 x 12 cm in size, 270 g in weight with necrotic region induced by preoperative radiation therapy. We made the diagnosis of solitary fibrous tumor of the thymic area by pathological examination and immunohistochemical study. SFT most frequently arises in the pleura and is less frequently observed in the pericardium and peritoneum. But SFT of the mediastinum has been rarely reported in the world and this is the second case in Japan. PMID- 8360553 TI - [Concept and etiological mechanism of cor pulmonale]. PMID- 8360554 TI - [Clinical condition and physiopathology of patients with cor pulmonale]. PMID- 8360555 TI - [Physiopathology and diagnosis of hypoxic pulmonary vasoconstriction]. PMID- 8360556 TI - [Diagnosis of cor pulmonale by hematologic tests, thoracic radiography and ECG]. PMID- 8360557 TI - [Diagnosis of cor pulmonale by radioisotope angiography]. PMID- 8360558 TI - [Diagnosis of cor pulmonale by echocardiography]. PMID- 8360559 TI - [Diagnosis of cor pulmonale by heart catheterization]. PMID- 8360560 TI - [Epidemiology and prognosis of cor pulmonale]. PMID- 8360561 TI - [Drug therapy of cor pulmonale]. PMID- 8360562 TI - [Oxygen therapy of cor pulmonale]. PMID- 8360563 TI - [Guidance of life for patients with cor pulmonale]. PMID- 8360564 TI - [Surgical treatment of cor pulmonale]. PMID- 8360565 TI - [Left ventricular function in patients with cor pulmonale]. PMID- 8360566 TI - [Pulmonary thromboembolism and IgE]. PMID- 8360567 TI - [Adult respiratory distress syndrome and cell adhesion molecules]. PMID- 8360569 TI - [Pulmonary hemodynamics following pneumonectomy]. PMID- 8360568 TI - [Obstructive sleep apnea syndrome and right heart function]. PMID- 8360570 TI - [Physiopathology of pulmonary circulatory disorders. Discussion]. PMID- 8360571 TI - [A case of acute kidney failure complicated with rhabdomyolysis in alcoholics]. PMID- 8360572 TI - [A case of primary idiopathic hypothyroidism showing macro-CPK type 1]. PMID- 8360573 TI - [A male case of primary biliary liver cirrhosis found in the course of psoriasis]. PMID- 8360574 TI - [A case of Addison's disease associated with hypogonadotropic hypogonadism]. PMID- 8360575 TI - [A case of Dejerine-Sottas disease with central nervous system involvement]. PMID- 8360576 TI - [Pulmonary intravascular macrophages]. PMID- 8360577 TI - [Insulin and insulin receptor disorders]. PMID- 8360578 TI - Antibody production in the baculovirus expression system. AB - The proven ability of insect cells to produce murine and human antibodies renders the baculovirus system amenable to the synthesis of both naturally occurring antibodies and designed mutants. Study of these antibodies should provide a basis for rational antibody design useful in human therapy. PMID- 8360579 TI - Oligonucleotide-directed mutagenesis of antibody combining sites. AB - We review here our attempts to achieve a better understanding of the structure- function relationship of antibody combining sites, and to gain insights into the engineering of antibodies with desired specificity and affinity. We have focused on a model system--antibodies to the hapten p-azophenylarsonate (Ars) derived from A/J mice. Oligonucleotide-directed mutagenesis was used to alter the sequence of the variable region genes of such anti-Ars antibodies. Mutant antibodies were generated in hybridoma cells following transfection of the altered genes, and the effects of the primary structure changes on antibody specificity, affinity, and idiotypic expression were assessed. These studies suggest that an antibody combining site with basic specificity for an antigen could be created by introducing a set of a few amino acid residues in the complementarity determining regions, and that the affinity of such a site could be improved one substitution at a time in a sequential manner. PMID- 8360580 TI - Increased antibody affinity and specificity by codon-based mutagenesis. PMID- 8360581 TI - Characterization and applications of antibodies produced in plants. AB - Of the variety of compounds expressed in transgenic plants, antibodies offer probably the widest range of applications. The antibodies appear to possess all of the functional characteristics of antibody derived from hybridoma cells, although further study will be required to determine the effect of the difference in heavy chain glycosylation. More work will also be directed toward the assembly, accumulation, stability and secretion of plant antibodies. The effect of the signal sequence on the expression and assembly of antibodies has been shown and further methods of optimizing transgenic protein accumulation in plants almost certainly exist. Plant antibody technology is still in its infancy. However, it offers enormous potential in "mix-and-match" antibody engineering, and the construction of multimeric immunoglobulin complexes may be feasible relatively easily, for the first time. Furthermore, as there is an enduring interest in using antibodies for therapeutic purposes, agricultural production and distribution offers a means of obtaining large quantities of antibodies at a relatively low cost. PMID- 8360582 TI - Combinatorial libraries. AB - Combinatorial antibody libraries, in which PCR amplified immunoglobulin light and heavy chain DNA are randomly recombined irrespective of their pairing in vivo into a vector and subsequently expressed in E. coli, have quickly become a very productive tool to generate monoclonal antibodies from various species. It has been drastically improved by utilizing phage display technologies in the selection process of specific antibodies. A brief summary of current techniques, critical published experiments showing the versatility of these systems with emphasis on human antibodies and discussions on chain preference, affinity maturation and the advent of semisynthetic and non-immune libraries will be presented. PMID- 8360583 TI - Chimeric antibodies. PMID- 8360584 TI - Hybrid antibodies. AB - One of the major advantages of genetic engineering is the ability to produce novel, hybrid antibodies. Hybrid antibodies can be assembled using fragments from different antibodies with the objective of assembling novel combinations of antibody-related effector functions. To efficiently achieve this goal it is necessary to have a precise understanding of the structure-function relationships within the antibody molecule. Secondly, it is possible to produce hybrids of antibodies with non-immunoglobulin proteins thereby achieving unique combination of functional properties. In this case it is necessary to consider both the desired functional properties and the means of assembling the protein components so as to maintain these properties. In all cases it is necessary to have the cloned gene segments, appropriate vectors and expression systems. PMID- 8360585 TI - Bispecific antibodies in lymphoma. PMID- 8360586 TI - Medical applications of single-chain antibodies. AB - A single-chain antibody or single-chain Fv (sFv) incorporates the complete antibody binding site in a single polypeptide chain of minimal size, with an approximate molecular weight of 26,000. In antibodies, the antigen combining site is part of the Fv region, which is composed of the VH and VL variable domains on separate heavy and light chains. Efforts over nearly two decades have indicated that Fv fragments can only rarely be prepared from IgG and IgA antibodies by proteolytic dissection. Beginning in 1988, single-chain analogues of Fv fragments and their fusion proteins have been reliably generated by antibody engineering methods. The first step involves obtaining the genes encoding VH and VL domains with desired binding properties; these V genes may be isolated from a specific hybridoma cell line, selected from a combinatorial V-gene library, or made by V gene synthesis. The single-chain Fv is formed by connecting the component V genes with an oligonucleotide that encodes an appropriately designed linker peptide, such as (Gly4-Ser)3. The linker bridges the C-terminus of the first V region and N-terminus of the second, ordered as either VH-linker-VL or VL-linker-VH. In principle, the sFv binding site can faithfully replicate both the affinity and specificity of its parent antibody combining site, as demonstrated in our model studies with the 26-10 anti-digoxin sFv. Furthermore, the sFv remains stable at low concentrations that promote VH and VL dissociation from the Fv heterodimer, resulting in loss of Fv binding. Intravenously administered sFv proteins exhibit accelerated biodistribution and exceptionally fast clearance compared to IgG or Fab. These pharmacokinetic properties allow rapid imaging by sFv, which therefore may be labeled with a short-lived isotope such as Tc-99m. Expression of a single gene product from fused sFv and effector genes facilitates immunotargeting of the effector protein, as shown for single-chain Fv toxin fusion proteins. PMID- 8360587 TI - Recent developments in catalytic antibodies. PMID- 8360588 TI - Humanized antibodies: enhancing therapeutic utility through antibody engineering. AB - The promise of antibody therapeutics has been greatly expanded by the development of monoclonal antibody technology and more recently antibody humanization. By transferring the mouse antibody binding site into a human antibody gene, we can engineer a "human antibody" which retains the specificity and biological effects of the original mouse antibody but has the potential to be nonimmunogenic in humans. Additionally, antibody effector functions can be improved through manipulation of the antibody constant region genes. We have produced a humanized version of OKT3 with human IgG4 and kappa constant regions. This antibody retains all of the in vitro characteristics of murine OKT3 including induction of cytokine release and T cell activation markers. Humanized OKT3 has an affinity of 1.4 x 10(9) M-1 relative to a 1.2 x 10(9) M-1 affinity of murine OKT3. Substitution of a glutamic acid for leucine at residue 235 in the antibody constant region abrogates FcR I binding and causes a marked reduction of T cell activation. The humanized FcR mutant of OKT3 has potential to be an improved therapeutic for transplantation and may have applications in autoimmune disease treatment. PMID- 8360589 TI - Chimeric T cell receptor-immunoglobulin molecules: function and applications. AB - The antigen-specific receptors on T and B cells are related by sequence similarities, mechanisms for the generation of diversity, and a common protein domain structure. In contrast, the form of antigen recognition for T- and B-cell antigen receptors is entirely different. Whereas the B cell antigen receptor, i.e., membrane-bound immunoglobulin (Ig), has the potential to recognize a vast diversity of chemical determinants, the T cell antigen receptor (TCR) invariably recognizes oligomeric peptides bound to major histocompatibility complex molecules. A question is whether the variable domains of the TCR and Ig are similar in structure, and if so, can they be substituted one for the other. Recent experiments show that, in some combinations, the variable region of Ig can substitute for the variable region of a TCR, and convey, to a reactive T lymphocyte, the antigen specificity of an Ig molecule. This type of receptor engineering may have interesting applications in disease therapy. PMID- 8360590 TI - Effects of in vitro exposure to arachidonic acid on TNF-alpha production by murine peritoneal macrophages. AB - Modifying the fatty acid composition of macrophages through diet can significantly alter some of their functions, such as tumoricidal capacity and tumor necrosis factor alpha (TNF-alpha) production. The mechanism of that modification, however, is unknown. In this report, we provide evidence that fatty acids added to macrophages in culture can significantly alter macrophage TNF alpha production. For example when inflammatory macrophages were incubated with various doses of arachidonic acid [20:4(n-6)] during activation with lipopolysaccharide (LPS), we observed a dose-dependent decrease in the level of bioactive TNF-alpha with complete inhibition at 2-5 microM. This inhibition was specific for 20:4(n-6) because in vitro treatment with other fatty acids, such as eicosapentaenoic [20:5(n-3)] or docosahexaenoic [22:6(n-3)] acids, had differential effects. The inhibitory action of 20:4(n-6) did not involve toxicity because cell viability was not affected and in vitro interferon-gamma and lipopolysaccharide (LPS) activation of macrophages for killing of P815 tumor targets was not altered. Inhibition by 20:4(n-6) occurred posttranscriptionally, and could be reversed when macrophages were treated with indomethacin during activation. Arachidonic acid treatment also significantly increased the production of immunoreactive prostaglandin E2 (PGE2) by LPS-treated and untreated macrophages. These results suggest that in vitro treatment of macrophages with 20:4(n-6) may inhibit TNF-alpha production through an alteration in the levels of PGE2 at a posttranscriptional level. These results provide evidence that some dietary fats may affect macrophage activity through modification of eicosanoid synthesis. PMID- 8360591 TI - Calcium-binding myeloid protein (P8,14) is phosphorylated in fMet-Leu-Phe stimulated neutrophils. AB - In this report, we show that the p14 subunit of calcium-binding myeloid protein complex (p8,14) is phosphorylated in human neutrophils stimulated with either fMet-Leu-Phe, phorbol myristate acetate, or a calcium ionophore. Trifluoperazine, a calmodulin antagonist, caused hyperphosphorylation of p14 in intact resting neutrophils. Preincubation of resting cells with 10-20 nM calyculin A, a potent protein phosphatase inhibitor, also caused enhanced labeling of p14, which was further progressively increased on stimulation with fMLP. Thus, the phosphorylation level of p14 in resting as well as in stimulated neutrophils appears to be controlled by an active protein phosphatase. The phosphorylation of p14 by a chemoattractant and by a phorbol ester is a novel finding supporting the current belief that p8,14 myeloid protein may play an important role in the metabolism of myeloid cells. PMID- 8360592 TI - Retinoic acid inhibits interleukin-1-induced cytokine synthesis in human monocytes. AB - Retinoids are pluripotent morphogens whose effects on gene expression are mediated through specific intracellular receptors. They have certain anti inflammatory effects in vivo, the basis of which is not clearly understood. To characterize mechanisms involved with potential anti-inflammatory actions of retinoids, we studied the effects of retinoic acid (RA) on cytokine production in human peripheral blood monocytes. RA differentially modulated the expression of interleukin-1 beta (IL-1 beta), IL-6, and IL-8 mRNAs depending on the inducing stimulus. While phorbol myristate acetate-induced IL-1 beta and IL-8 mRNA expression was increased by RA (IL-6 could not be induced by this pathway in monocytes), IL-1 beta-induced expression of IL-1 beta and IL-8 was markedly reduced and IL-6 gene expression was almost completely suppressed. Lipopolysaccharide (LPS)-induced cytokine synthesis was only slightly reduced and this required a longer preincubation (> 72 h) of monocytes with RA. IL-1-induced de novo synthesis of IL-6 protein and secretion of biologically active IL-6 were also inhibited by RA. The inhibition pattern of RA was different from that of dexamethasone, which inhibited both IL-1 and LPS effects. In summary, our data show that RA regulates monocyte cytokine expression selectively in response to the particular stimuli. Inhibition of IL-1 beta-induced cytokine expression provides a mechanism that can explain some of the anti-inflammatory effects of RA. PMID- 8360593 TI - Suppressive effect of interleukin-4 on the differentiation of M1 and HL60 myeloid leukemic cells. AB - The effect of interleukin-4 (IL-4) on the proliferation and differentiation of myeloid leukemic cell lines was studied in vitro. A culture of murine myeloid cell line, M1, with lipopolysaccharide (LPS) from Escherichia coli, induced differentiation into macrophages that expressed Fc receptors and phagocytic activity. IL-4 did not induce the differentiation of M1 cells but inhibited the differentiation of M1 cells induced with LPS. On the other hand, LPS arrested the proliferation of M1 cells. IL-4 had no effect on the proliferation of M1 cells but restored the LPS-induced arrest of the proliferation of M1 cells. IL-1, IL-6 and tumor necrosis factor alpha (TNF-alpha) also induced the differentiation of M1 cells into macrophages and arrested proliferation. IL-4 suppressed the IL-1-, IL-6-, and TNF-induced differentiation of M1 cells and restored the arrested proliferation with IL-1, IL-6, and TNF. Similar results were obtained with human myeloid cell line HL60. These results suggest that IL-4 has a suppressive effect on the differentiation of myeloid cells into macrophages. PMID- 8360594 TI - Fibrosarcoma-induced increase in macrophage tumor necrosis factor alpha synthesis suppresses T cell responses. AB - Tumors down-regulate T cell responses partly by increasing macrophage (m phi) production of the suppressive molecule prostaglandin E2 (PGE2). Because tumor growth increases m phi tumor necrosis factor alpha (TNF-alpha) production and TNF alpha stimulates m phi PGE2 synthesis, we examined the contribution of TNF-alpha to fibrosarcoma-induced m phi-mediated suppression of alloreactive CD4+ T cell proliferation. We showed that tumor-bearing host (TBH) m phi s express high levels of TNF-alpha mRNA, which leads to increased lipopolysaccharide-induced TNF alpha production. Tumor cells were directly involved in m phi TNF-alpha synthesis because fibrosarcoma cells induced normal host (NH) m phi s to produce TNF-alpha. Addition of TBH m phi s to allogeneic mixed lymphocyte reaction (MLR) cultures suppressed CD4+ T cell proliferation more than NH m phi s. The neutralization of endogenous TNF-alpha activity with anti-TNF-alpha antibody (Ab) treatment reversed TBH, but not NH, m phi-mediated suppression. Conversely, exogenous TNF alpha increased NH or TBH m phi-mediated suppression but stimulated T cell proliferation without m phi s. Kinetic treatment of MLR cultures with anti-TNF alpha Ab or TNF-alpha showed that TNF-alpha production and activity occurred at the beginning of T cell proliferation. When arachidonic acid metabolite synthesis was inhibited, TNF-alpha-induced suppression was blocked in NH m phi-containing cultures and completely reversed in TBH m phi-containing cultures. A PGE2 specific enzyme-linked immunosorbent assay showed that TNF-alpha addition increased PGE2 production in NH m phi-containing cultures to that of TBH m phi containing cultures. Exogenous PGE2 did not affect the TNF-alpha enhancement of T cell proliferation without m phi s. Therefore, suppression induced by TNF-alpha was caused by increased m phi PGE2 production and not by TNF-alpha in concert with PGE2. Even though TNF-alpha is known to enhance lymphocyte proliferation, we show that in the presence of m phi s, the main TNF-alpha producers, TNF-alpha suppresses T cell proliferation. Perhaps increased TNF-alpha production during pathological states, such as cancer, triggers the initial stages of suppression. PMID- 8360595 TI - Suppression of human IgE antibody forming cell responses by IL-6. AB - To study the effects of cytokines on human IgE antibody forming cells (AFCs), log phase U266 myeloma cells (3 x 10(3)/ml), which secrete immunoglobulin E (IgE), were cultured for 0-24 h with and without cytokine or with or without antibodies against various cytokines. The numbers of IgE AFCs were determined in ELISPOT assay. We found that interleukin-6 (IL-6) suppressed (to 95%) whereas anti-IL-6 increased (to 148%) the numbers of IgE AFCs and that both worked in a dose dependent fashion. IL-4 and interferon-gamma (IFN-gamma) also suppressed IgE AFC responses in a dose-dependent fashion. However, antibodies to these cytokines had no effect. In contrast, IFN-alpha increased (to fourfold) the numbers of IgE AFCs in a dose-dependent fashion. The data are the first to show a suppressive effect of IL-6 on human IgE responses and may also suggest a role for IL-6 in the treatment of atopic disease. PMID- 8360597 TI - Apical third instrumentation of curved canals with K-type and canal master instruments. AB - Forty acrylic blocks with curved canals were divided into two groups of 20 each. One group had canals with 30-degree curvature and the other with 45-degree curvature. Each group was divided into two subgroups of 10 blocks each. One subgroup was instrumented with precurved Kerr files and the other was instrumented with Canal Master hand instruments. The efficiency of the two instruments for preparing the apical third of curved canals was compared. In plastic blocks, Canal Master caused less transportation and was more suitable for instrumenting the canals. PMID- 8360596 TI - Movement of resin cement components through acid-treated dentin during crown cementation in vitro. AB - This study examined the hypothesis that components of crown cements may be forced through acid-treated dentin during cementation. Freshly extracted, human third molar teeth were prepared to accept full crowns. Roots were removed to allow irrigation of the pulp chamber with saline before, during, and after crown placement with resin dentin bond and resin composite cement. Saline samples were collected and analyzed by high performance liquid chromatography to identify and quantify resin components arriving in the pulp space. Two components of the bond cement system used were identified in the pulp space samples immediately after crown cementation. These were 2-hydroxyethylmethacrylate and 2,2-bis[4-(2-hydroxy 3-methacryloxypropoxy)phenyl]propane. The amounts of these components in the pulp space decreased when the bonding agent was cured prior to crown placement. The results of this study supported the hypothesis that crown cementing components may flow through acid-treated dentin during crown cementation. PMID- 8360598 TI - Smear layer removal with different concentrations of EDTA-ethylenediamine mixtures. AB - The purpose of this study was to observe the effectiveness of EDTA and ethylenediamine mixtures in removing the smear layer from prepared root canal walls following instrumentation. Thirty-five freshly extracted, single-rooted maxillary anterior teeth were used. After the preparation of access cavities and establishing the working length, the apical foramen of each canal was sealed with casting wax. All canals were then sequentially enlarged with K-type files to size 50. The sample was divided into seven groups of five teeth. The teeth in the control group were irrigated with saline solution. The specimens in the other groups were irrigated with 10 and 20 ml of three different EDTA-ethylenediamine mixtures. A scanning electron microscopic evaluation of the canal walls following irrigation showed that the superficial layer was totally removed and the openings of the dentinal tubules were patent. Only at the coronal third of the teeth in group 4 and the apical thirds in groups 2 and 4 was a moderate smear layer observed. The most favorable results were obtained with groups 5, 6, and 7. The results show that the smear layer can be totally removed by using 10 ml of a four to-three by volume mixture of EDTA and ethylenediamine for irrigation of instrumented root canals. PMID- 8360599 TI - Effects of the XeCl excimer laser on Streptococcus mutans. AB - The effect of XeCl excimer laser irradiation on the growth of Streptococcus mutans in liquid media and on agar plates was studied. Bacterial suspensions of S. mutans were placed in 96 wells of well culture plates. The contents of 72 wells (three experimental groups of 24 wells each) were lased for different time durations (2, 4, and 8 s). The remaining 24 wells were left unlased to be used as controls. Samples were withdrawn from all wells and examined for surviving bacteria. In addition, blood agar plates were inoculated with S. mutans and were lased with different energy densities (fluences). Zones of bacterial inhibition were measured. Analysis of variance test was used to determine statistical differences. The bactericidal effect of the laser applications was directly related to the amount of radiation time. Laser irradiation for 4 and 8 s resulted in bactericidal effect that was statistically significant compared with no treatment or to 2-s exposure. The effect of different energy levels was studied by irradiating inoculated blood agar plates. The zones of inhibition produced by higher energy levels (0.5 J/cm2, 0.7 J/cm2, and 1.0 J/cm2) were larger in comparison to the lowest fluence used (0.1 J/cm2). Application of the laser to the surface of the agar plates produced an indentation with a surrounding halo. The indentations and the zones of inhibition were more pronounced as the fluences increased. Based on our results it appears that the XeCl 308-nm excimer laser can kill S. mutans. This effect should be tested on other bacteria commonly present infected root canals. PMID- 8360600 TI - Computerized analysis of the instrumentation of the root canal system. AB - A method is proposed for a three-dimensional visualization of the root canal system before and after the cleaning and shaping procedure to analyze the relationships of the root canal walls. The first part of the study provided cross sections of the root perpendicular to the root canal. A system for remounting the sections of the root before and after instrumentation was set up. Micrographs of the sections were transferred to a graphics computer which rebuilt and elaborated the sections, providing a three-dimensional model of the root with the image of the root canal system before and after instrumentation. This experimental computerized model enables sections of all kinds to be produced, with great possibilities for measurement and analysis. PMID- 8360601 TI - Effect of various types of sodium perborate on the pH of bleaching agents. AB - Time-dependent changes in the pH value of various types of sodium perborate solutions used as bleaching agents were evaluated. Sodium perborate-monohydrate (MH), sodium perborate-trihydrate (TRH), and sodium perborate-tetrahydrate are available. Each perborate was mixed with 10%, 15%, or 30% fresh hydrogen peroxide or with bidistilled water in a powder to liquid ratio of 2 g:1 ml, respectively. The pH values were recorded at baseline and after 1h, 1 day, 3 days, and 7 days, respectively. At baseline the pH values of MH, TRH, and tetrahydrate in conjunction with 30% H2O2 were 8.7, 7.0, and 7.5, respectively. The pH increased significantly with decreasing concentrations of H2O2. For TRH, MH, and tetrahydrate mixed with bidistilled water more alkaline values were measured at baseline and after 1 h. Due to solidification of the samples, the pH could not be determined for MH starting day 1 and for TRH starting day 3. In conclusion, the pH of bleaching pastes depends on the content of water of crystallization in sodium perborate, H2O2 concentration, and time of measurement. The bulk of the mixtures recorded reached alkaline pH values of 10 to 11. It is recommended that the pH of the mixture being used be checked to avoid potential postbleaching root resorption. PMID- 8360602 TI - Accuracy of an electronic apex locator: a clinical evaluation in maxillary molars. AB - Identifying the point of apical termination in endodontic therapy is of indisputable importance. In this study, the accuracy of an electronic apex locator was clinically evaluated in 26 maxillary molar teeth, and comparisons were made to the radiographic and direct anatomical measurements of tooth length. The results indicated that a higher percentage of acceptable measurements were obtained by the radiographic method as compared with the electronic method (88.5% to 73.1%). Additionally, inaccurate electronic estimates were long in every instance. The results of this study do not support the replacement of radiographs with electronic devices in endodontic therapy. PMID- 8360603 TI - Prevention of apical periodontal ligament pain: a preliminary report of 100 vital pulp cases. AB - A preliminary study was conducted in a private practice office to determine the incidence of postoperative pain in 100 vital pulp cases. An ophthalmic dexamethasone-neomycin solution was introduced within the root canal during the complete cleaning and shaping procedure with the purpose of premedicating and preventing apical periodontal ligament inflammation and pain. The postoperative pain outcome was compared between cases premedicated with intracanal dexamethasone-neomycin solution alone and in combination with an oral administration of Mesulide. Moderate pain was reported in 10 cases and tooth sensitivity in 13. The clinical results indicated no report of severe pain. PMID- 8360604 TI - A two-rooted mandibular incisor. AB - A case report is presented demonstrating a two-rooted mandibular incisor. Because of prosthetic considerations, endodontic therapy was not performed and the tooth was extracted. However, this case reinforces the importance of proper radiographic techniques and interpretation in detecting radicular anomalies. PMID- 8360605 TI - Pulp obliteration: a histological study. AB - Pulp obliteration is a very rare occurrence that is most frequently caused by trauma. A 58-yr-old female patient had a generalized pulp obliteration that involved all maxillary and mandibular teeth. One tooth was extracted due to an extensive carious lesion and it was processed by a cutting-grinding technique. It was possible to observe the complete obliteration of the pulp chamber, which was filled in part by reparative dentin and in part by a calcified tissue with a concentric layers structure with no tubular pattern. The root canals were almost completely obliterated by an amorphous calcified material. PMID- 8360606 TI - The flare-up index: a quantitative method to describe the phenomenon. AB - Acute exacerbation of symptoms during the inter-appointment time interval of endodontic treatment is a well-known complication. The phenomenon is termed "flare-up" by most researchers and clinicians, although the exact definition of it differs from one author to another, making it difficult to compare the results of the studies. The suggested flare-up index may be the way to build a common language that will enable the dental community to measure and study more of this phenomenon. PMID- 8360607 TI - Assessing the evidential value of DNA profiles matching without using the assumption of independent loci. AB - DNA profiling allows determination of the alleles at multiple loci on an individual's genome. The frequencies of these alleles are then estimated from a sample drawn from the population. If the occurrences of alleles at different loci are independent, the frequencies may be multiplied together to give an estimate of the probability of DNA from a randomly-chosen member of the population matching the DNA in question. However, there is doubt as to whether the assumption of independence can be justified. This paper discusses a method of calculating the probability of a match that does not require the assumption of independence. A suitable set of criteria is also derived that offer an objective approach to the determination of a match from two DNA samples. PMID- 8360608 TI - Differentiation of alpha-amylase from various sources: an approach using selective inhibitors. AB - A radial diffusion assay in an agarose/starch gel utilizing crude kidney bean extract and a commercially prepared alpha-amylase inhibitor isolated from wheat seeds was developed and assessed to determine its ability to differentiate alpha amylase from various sources. Kidney bean extract was found to have a greater inhibitory effect on AMY2, while the wheat lectin inhibitor was found to have a greater inhibitory effect on AMY1. Neither inhibitor was found to have any effect on commercially prepared bacterial alpha-amylase extract in both liquid preparations and dried stains. Mixtures of varying concentrations of pancreatic and salivary extracts also gave interpretable results. Additionally, dried stains prepared from human body fluids having high levels of AMY2 were differentiated from dried stains prepared from human body fluids containing high levels of AMY1. PMID- 8360609 TI - Salmonella reference collection B (SARB): strains of 37 serovars of subspecies I. AB - A reference collection of 72 strains representing 37 serovars of Salmonella subspecies I has been established for use in research on genetic and phenotypic variation in natural populations. Included are isolates of the host-adapted serovars S. choleraesuis, S. dublin, S. gallinarum, S. paratyphi A, S. paratyphi B, S. paratyphi C, S. pullorum, S. sendai, S. typhi and S. typhisuis, as well as strains of S. enteritidis, S. typhimurium, and other commonly recovered serovars with broad host ranges. The isolates were characterized by enzyme electrophoresis for allelic variation in 25 chromosomal genes and represent 71 distinctive multilocus genotypes (electrophoretic types or ETs). Genetic relationships among the ETs are indicated in an evolutionary tree constructed by the neighbour joining method from a matrix of Nei's standard genetic distance. PMID- 8360610 TI - Colonization of chicks by motility mutants of Campylobacter jejuni demonstrates the importance of flagellin A expression. AB - Campylobacter jejuni strain 81116 contains two flagellin genes, flaA and flaB. Wild-type (WT) bacteria express flaA only, but flaB can be expressed under certain conditions. We have determined the importance of flagella for colonization of the avian caecum, which appears to be the natural environment for these bacteria. Mutants in which flaA or flaB, or both had been inactivated, and motility variants, were investigated. Flagella are not a requisite for colonization, but mutants lacking both flagellin genes colonized less efficiently than WT. Inactivation of the flaB gene, which had no effect on bacterial motility, enhanced chicken caecal colonization 1000-fold compared to WT. A variant (SF-1) with flagella composed of flagellin A, but with poor motility, also colonized better than WT. Conversely, mutants with an inactivated flaA gene colonized 100- to 1000-fold less efficiently than WT, regardless of their motility conferred by truncated or full-length flagellin B flagella. These results suggest that the presence of flagellin A, rather than motility, is essential for optimal bacterial colonization of chicken caeca. PMID- 8360611 TI - Purification and characterization of the extracellular aspartyl proteinase of Candida albicans: removal of extraneous proteins and cell wall mannoprotein and evidence for lack of glycosylation. AB - Aspartyl proteinase (AP) is an extracellular enzyme of Candida albicans implicated as a pathogenic factor. Previous reports on the purification and characterization of AP suggested that a single DEAE-Sephadex chromatographic step was sufficient for the removal of extraneous proteins and that the final product was glycosylated. We purified AP using a chromatographic series consisting of DEAE-Sephadex A25, Sephadex G75 and rechromatography on DEAE-Sephadex A25. Use of DEAE-Sephadex alone did not remove extraneous proteins and removed little contaminating mannoprotein (MP). The addition of a Sephadex G75 column to the purification scheme removed the majority of contaminating MP and proteins. The final DEAE-Sephadex A25 chromatographic step resulted in (a) removal of detectable extraneous proteins, (b) removal of immunologically detectable MP by dot blot and Western blot enzyme immunoassay, (c) loss of periodic acid-silver stain positivity, and (d) a high AP yield (1295 U l-1) and specific activity (1749 U mg-1). We conclude that a single DEAE-Sephadex A25 purification step is insufficient to remove extraneous proteins and MP, which could interfere with the production of AP-specific antibodies and the dissection of moieties responsible for immune reactivity. Reports of periodic acid-Schiff or anthrone positivity of AP preparations may reflect the presence of extraneous MP, which can be removed by the chromatographic series we describe. PMID- 8360612 TI - Induction of extracellular proteinase in Candida albicans. AB - Pulse-chase experiments indicated that the extracellular proteinase (EPR) of Candida albicans originates as a 45 kDa precursor protein which is processed to a 43 kDa protein prior to secretion. Secretion was routinely stimulated in EPR induction medium which contains bovine serum albumin (BSA) and glucose. Although EPR was not induced without glucose as a carbon source, EPR secretion was induced without the addition of BSA or other nitrogen sources. Furthermore, it was shown that EPR production was not induced at pH > 6.0, irrespective of the presence of a nitrogen source. This suggests that medium pH may act directly upon EPR induction, and not as a secondary effect of the nitrogen supply from EPR-mediated protein digestion, which exhibited a pH optimum of around pH 3.5. When germ tube induced cells were transferred to EPR induction medium, EPR was not induced. Thus, EPR production and germ tube formation may not be induced by the same conditions. We speculate that EPR production and germ tube formation do not co operate in the invasive process but play different and separate roles. PMID- 8360613 TI - Multiple chromosomal and phenotypic changes in spontaneous mutants of Candida albicans. AB - Previous studies have revealed the occurrence of multiple chromosomal alterations among spontaneous colony form mutants and clinical isolates of Candida albicans. In this report we show that such karyotype alterations are also seen in spontaneous and induced non-germinative mutants of the fungus. To determine if phenotypic changes other than colony form and microscopic morphology accompanied the rearrangements of the electrophoretic karyotype, we studied the following characteristics of the non-germinative and some of the colony form mutants: formation of pseudohyphae, chlamydospore production, germ tube formation, colony morphology, auxotrophy, growth at various temperatures, and colony morphology and pigment formation on selected media (bismuth sulphite and Phloxine B). We established that phenotypic and karyotypic variability among spontaneous, non germinative mutants was no different than such variability among spontaneous colony form mutants. Thus, non-germination may represent another phenotypic consequence of genomic instability in C. albicans. The variability in different phenotypic attributes that occurred amongst the mutants was not associated with any given karyotype. Moreover, neither the low nor the high phenotypic variabilities observed were explained by the relatively high number of alterations in a limited number of chromosomes. PMID- 8360615 TI - Transcriptional regulation of an endoglucanase and a cellodextrinase gene in Ruminococcus flavefaciens FD-1. AB - A gene which encodes a 35 kDa protein with both carboxymethylcellulase and xylanase activity was cloned from Ruminococcus flavefaciens FD-1 and the nucleotide sequence determined. The FD-1 gene, celE, and the celA gene, which encodes a cellodextrinase, were used as probes to analyse transcription in R. flavefaciens grown under different conditions. Transcription of both genes was induced when cellulose was added to cells growing in cellobiose. This induction continued after cellulose depletion and after cell division had ceased. Transcription of both genes was also induced by cellotriose, although the effect was not as pronounced as induction by cellulose and was greater for the celA gene than for the celE gene. PMID- 8360614 TI - Identification of two laccase genes in the cultivated mushroom Agaricus bisporus. AB - A cDNA library was constructed in lambda gt11 using mRNA from 11-d-old mycelium of Agaricus bisporus. Three clones containing laccase sequence were identified using an affinity-purified anti-laccase antibody. From one of these clones, a 333 bp sequence was used to identify further cDNA clones (including one which is close to full length) and a genomic clone. The coding sequences found were of two similar but not identical versions with differences at 36 out of 520 residues of deduced amino acid sequence. The laccase genes each encode a sequence expressed as a 2.3 kb mRNA, specifying a 520 residue polypeptide including a 19 amino acid residue signal peptide that is absent from the N terminus of the mature (extracellular) protein. The coding sequence of lcc1 is interrupted by 14 short introns. The lcc1 and lcc2 genes are not allelic as they do not segregate in uninucleate spores derived from a four-spored basidium. Comparison of the deduced amino acid sequences with that of the other fungal laccases that have been cloned, and with the very similar ascorbate oxidases from higher plants shows that whilst some sequence is absolutely conserved at and around the amino acid residues involved in copper binding, the overall sequence similarities are low. PMID- 8360616 TI - Cloning, sequencing and biochemical characterization of xylose isomerase from Thermoanaerobacterium saccharolyticum strain B6A-RI. AB - The xylose isomerase gene from Thermoanaerobacterium saccharolyticum strain B6A RI was cloned by complementation using Escherichia coli xyl-5 mutant strain HB101. One positive clone was detected and the recombinant plasmid, pZX16, was isolated. The clone contained the vector pUC18 and an insert fragment of 4.5 kb. The cloned xylose isomerase gene (xylA) was expressed constitutively in E. coli. The gene contained one open reading frame (ORF) of 1317 bp, which corresponds to 439 amino acid residues. The molecular mass of the gene product was calculated to be 50474 Da from the deduced amino acid sequence. A putative promoter region (Pribnow box), TATAATATATAAT, which repeated twice at the -10 region in E. coli, was found 25 bp upstream of the ribosomal binding site. The deduced amino acid sequence of T. saccharolyticum strain B6A-RI xylose isomerase exhibited very high homology to those from Thermoanaerobacterium thermosulfurigenes 4B (formerly Clostridium thermosulfurogenes 4B) and Thermoanaerobacter ethanolicus 39E (formerly Clostridium thermohydrosulfuricum 39E). Codon usage in xynA, xynB and xylA showed a clear propensity for AT-containing isocodons. The native molecular mass of the purified recombinant thermostable xylose isomerase was 200 kDa, and the enzyme was a tetramer comprised of identical subunits. The apparent temperature and pH optima for activity of the cloned xylose isomerase were 80 degrees C and 7.0 to 7.5, respectively. PMID- 8360617 TI - Genetic organization, sequence and biochemical characterization of recombinant beta-xylosidase from Thermoanaerobacterium saccharolyticum strain B6A-RI. AB - Endoxylanase (xynA) and beta-xylosidase (xynB) genes from Thermoanerobacterium saccharolyticum were subcloned from a cosmid clone (pXDM1) to generate pXPH3. The nucleotide sequence of a PstI-HindIII fragment in pXPH3 that contained xynB revealed an open reading frame (ORF) of 1500 bp encoding a 55 kDa protein. Another open reading frame (ORF1) of unknown function was found 21 bp downstream from the first stop codon of xynB. xynB, ORF1 and xynA had the same direction of transcription. xynB from T. saccharolyticum strain B6A-RI exhibited 45% amino acid similarity, with 18% amino acid identity to xynA of T. saccharolyticum strain B6A-RI, and 61% similarity and 37% identity with the beta-xylosidase gene from Caldocellum saccharolyticum. Recombinant beta-xylosidase was purified from E. coli (pXPH3) cells. The enzyme was a monomer with a molecular mass of 55 kDa. The specific activity and pH and temperature optima for hydrolysis of p nitrophenyl-beta-D-xylopyranoside (pNPX) were 5.53 U mg-1, 5.5 and 70 degrees C, respectively. The beta-xylosidase was stable at 65 degrees C, but lost activity at 85 degrees C. The purified enzyme had hydrolytic activity towards xylopentose, xylotriose, xylobiose and pNPX, but had no activity toward xylan. PMID- 8360618 TI - beta-Lactamase of Lysobacter enzymogenes: cloning, characterization and expression of the gene and comparison of the enzyme to other lactamases. AB - The gene for the periplasmic beta-lactamase of Lysobacter enzymogenes was isolated as part of a 1017 bp EcoRI fragment and the nucleotide sequence of the gene was determined. It has a G+C content of 71.5% and encodes a 27 amino acid signal sequence and the mature beta-lactamase of 276 amino acids which has a mass of 29,146 Da. The enzyme appears to be unique to L. enzymogenes but its amino acid sequence shows a high degree of homology with the amino acid sequences of the lactamase from Citrobacter diversus and other Class A beta-lactamases. The beta-lactamase gene of L. enzymogenes was expressed in Escherichia coli using pUC118 as the vector. The production of active beta-lactamase was highest after the active growth phase of the expression host and reached levels which were about three times higher than those obtained with L. enzymogenes. PMID- 8360619 TI - Processing and secretion by Escherichia coli of a recombinant form of the immunogenic protein MPB70 of Mycobacterium bovis. AB - The gene encoding an immunodominant secreted antigen, MPB70, of Mycobacterium bovis was cloned into the plasmid vector pBluescript II KS+ along with its native ribosome-binding site. In this construct translation of the protein in Escherichia coli was from the native AUG initiation codon and was directed by the mycobacterial ribosome-binding site. Two different molecular mass forms (26 kDa and 22 kDa) of MPB70 were observed in whole-cell pellets of recombinant E. coli. The difference in size indicates cleavage of the signal peptide of MPB70 by an endopeptidase of E. coli. MPB70 was secreted into the periplasm of recombinant E. coli, where the 22 kDa form of the protein was predominant. The culture filtrate contained only the 22 kDa form of the protein, which was soluble. The passage of MPB70 from the periplasm into the growth medium was found to be due, at least in part, to non-specific leakage of periplasmic proteins across the outer membrane associated with the expression of recombinant MPB70. PMID- 8360620 TI - Sensitivity of naturally occurring coliphages to type I and type II restriction and modification. AB - Protection against lethal infections by bacteriophage may seem the most likely role of restriction-modification (R-M) systems in bacteria and the reason for their evolution. There are, however, phenomena which question this phage-mediated selection hypothesis for the maintenance of extant R-M systems. Most prominent among these are the mechanisms phage have to avoid or otherwise limit the effects of the restriction endonucleases produced by their host bacteria. To evaluate the importance of these antirestriction mechanisms in Escherichia coli, we have examined the sensitivity of coliphage from natural and laboratory sources to a series of type I and II R-M systems. The results of our study indicate that, in vivo, restriction endonucleases have no effect on a substantial fraction of naturally occurring coliphage. The absence of restriction sites appears to be the most common reason why these phage are unaffected by type II restriction endonucleases, but other antirestriction mechanisms also operate. On the other hand, the frequency of naturally occurring coliphage sensitive to restriction appears sufficiently great for phage-mediated selection to be a viable hypothesis for the maintenance of R-M in E. coli and its accessory elements. PMID- 8360621 TI - Alterations in the cellular envelope of spontaneous IIIManL-defective mutants of Streptococcus salivarius. AB - In Streptococcus salivarius, the phosphoenolpyruvate: mannose phosphotransferase system (PTSMan) transports and concomitantly phosphorylates mannose, glucose, fructose and 2-deoxyglucose. PTSMan consists of a membrane Enzyme II and two forms of Enzyme III (IIIMan) having molecular masses of 38.9 kDa (IIIManH) and 35.2 kDa (IIIManL) respectively. We have previously reported the isolation of spontaneous mutants lacking IIIManL, and showed that they exhibited abnormal growth when cultured in mixtures of sugars containing glucose. The mutants also synthesize several cytoplasmic glucose-repressible proteins during growth on glucose and some of them constitutively express a fructose PTS which is induced by fructose in the parental strain. We have now investigated the properties and composition of the cellular envelope of three S. salivarius IIIManL-defective mutants (strains A37, B31 and G29) after growth on glucose. The mutants have altered sensitivity to various toxic compounds that interfere with cell-envelope functions. The mutants also exhibited altered membrane-protein profiles when analysed by two-dimensional PAGE and modified total lipid and phosphorus contents and lipid/protein ratio. In one mutant (strain G29), the proportion of the phospholipids separated by TLC was different from the parental strain. Electron microscopy indicated that one mutant (strain A37) possessed more fimbriae than the parental strain. The results suggested that these IIIManL-defective mutants were affected in a global regulatory gene controlling several cellular or physiological functions, many of these being related to the cellular envelope. PMID- 8360622 TI - Involvement of the accessory gene regulator (agr) in expression of type 5 capsular polysaccharide by Staphylococcus aureus. AB - The effect of an agr mutation on expression of type 5 capsular polysaccharide (CP) by Staphylococcus aureus Newman was investigated in different complex and synthetic media. CP expression by the agr mutant was strongly reduced in certain media but slightly in others, indicating that CP synthesis is positively controlled by agr. CP expression occurred in the post-exponential growth phase in both wild-type and mutant strains, suggesting that other regulatory systems could act in conjunction with agr. PMID- 8360623 TI - Oxygen inhibition of nitrogenase activity in Klebsiella pneumoniae. AB - A purpose-built oxystat has been used to study reversible inhibition of nitrogenase by O2 in the facultative anaerobe Klebsiella pneumoniae. C2H2 reducing activity in samples from either an anaerobic glucose-limited or an O2 limited diazotrophic chemostat culture was completely inhibited by exposure to a dissolved O2 concentration (DOC) of 1.5 microM or above. Subsequently, under anaerobic conditions, C2H2-reducing activity returned in the absence of de novo protein synthesis. The amount of activity returning never reached 100% of the initial anaerobic activity before O2 treatment. The degree of reversibility was inversely proportional to the log of DOC during exposure and was decreased by increasing the time of exposure to O2 (about 60% reversibility occurred after a 20 min exposure to 6 microM-O2). The failure to obtain complete recovery of activity was apparently not due to inactivation of the very O2-sensitive pyruvate flavodoxin oxidoreductase (nifJ product) which provides electrons for nitrogenase activity in vivo. Samples from the O2-limited culture behaved similarly to those limited by glucose. Thus, 'training' of the organism to use O2 during growth does not influence the tolerance of nitrogenase to O2. Since the behaviour towards O2 reported here for K. pneumoniae differs from that known to occur in Azotobacter, the mechanism of protection of nitrogenase from O2 damage may differ in these organisms. PMID- 8360624 TI - The role of lipoic acid in product formation by Enterococcus faecalis NCTC 775 and reconstitution in vivo and in vitro of the pyruvate dehydrogenase complex. AB - The role of the pyruvate dehydrogenase complex (PDC) in the formation of different fermentation products by Enterococcus faecalis was studied. This organism was grown on a semi-defined medium under various conditions in the presence or absence of lipoic acid, an essential cofactor of the enzyme complex. When grown on a medium without added lipoic acid, a very low activity, both in vivo and in vitro, of the PDC was observed. When pyruvate served as the energy source, lipoic acid was found to be essential for growth under anaerobic conditions at low culture pH values. The presence of lipoic acid in the culture medium had a marked effect on the production of acetoin: in the presence of lipoic acid, acetoin was produced only when the intracellular pyruvate concentration was relatively high, whereas in the absence of lipoic acid, acetoin was a common product. Under potassium-limited conditions, lactate was the main product and culture pH significantly affected the bacterial dry weight. After instantaneous addition of lipoic acid to a glucose+pyruvate-limited chemostat culture, an immediate activation of the PDC took place as deduced from the change in fermentation pattern. Reconstitution of the PDC by the addition of lipoic acid was also possible in cell-free extracts, although pre-incubation with ATP and lipoic acid for 90 min was necessary for maximal activation. The effects of an active PDC on product formation and the physiological role of the complex under anaerobic growth conditions are discussed. PMID- 8360625 TI - Microbial transformation of nitroaromatic compounds under anaerobic conditions. AB - The transformation of several mono- and dinitroaromatic compounds (tested at 50 200 microM) by methanogenic bacteria, sulphate-reducing bacteria and clostridia was studied. Some of the nitroaromatics tested were transformed chemically by 1.5 mM quantities of culture media reducing agents, like cysteine or sulphide. This abiotic reduction occurred at the o-nitro-groups preferentially. Nitrophenols, p nitroaniline and p-nitrobenzoic acid were completely transformed biologically into the corresponding amino derivatives. The nitroaromatics were transformed by all of the bacterial strains tested. While growing cells of sulphate-reducing bacteria and Clostridium spp. carried out nitroreduction, methanogen cells lysed in the presence of nitroaromatics. Nevertheless these culture suspensions converted nitroaromatics to the corresponding amino derivatives. This was also confirmed by crude cell extracts of methanogenic bacteria. The rate of nitroreduction by sulphate-reducing bacteria depended on the electron donors supplied and the cell density, with molecular hydrogen being the most effective donor of reducing equivalents. The toxicity of p-nitrophenol to some of the organisms tested depended on the concentration of the nitroaromatic compound and the type of organism. PMID- 8360627 TI - Partial purification and properties of carminomycin 4-O-methyltransferase from Streptomyces sp. strain C5. AB - A methyltransferase that acts on carminomycin and 13-dihydrocarminomycin, and that is postulated to be the terminal enzyme in the daunomycin biosynthesis pathway, was purified to near-homogeneity from the daunomycin- and baumycin producing Streptomyces sp. strain C5. The enzyme was obtained in approximately 5% yield with a purification of 114-fold in specific activity over the sample precipitated with 30-50% ammonium sulphate. Polyacrylamide gel electrophoresis under denaturing conditions indicated a subunit M(r) of about 41,000. The enzyme was shown by gel filtration chromatography to have an M(r) of approximately 166,000, suggesting that it is a homotetramer. Kinetic analysis indicated an affinity for S-adenosyl-L-methionine typical of antibiotic methyltransferases; the enzyme had a slightly higher affinity for carminomycin than for 13 dihydrocarminomycin. The reaction product from methylation of carminomycin was confirmed by chromatography and mass spectral analysis to be daunomycin. The purified enzyme did not catalyse methylation of the aglycones carminomycinone or 13-dihydrocarminomycinone. S-Adenosyl-L-homocysteine inhibited the methyltransferase, whereas homocysteine, adenosine, adenine, epsilon rhodomycinone, daunomycin, and daunomycinone showed little or no inhibitory activity. PMID- 8360626 TI - Relationships amongst some bacterial and yeast lactate and mandelate dehydrogenases. AB - Five yeast strains were isolated by enrichment culture on the basis of their ability to grow on mandelate and two of these strains were identified as Rhodotorula glutinis. In addition, a range of yeasts from culture collections was screened for growth on mandelate. The results suggest that mandelate utilization is a widespread but not universal characteristic within the genus Rhodotorula. Several of the yeasts contained an inducible NAD-dependent D(-)-mandelate dehydrogenase and an inducible dye-linked (presumably flavoprotein) L(+) mandelate dehydrogenase. All the D(-)-mandelate dehydrogenases from the yeasts showed immunological cross-reactivity with each other (as judged by both immunoinhibition and immunoblotting), as did all the yeast L(+)-mandelate dehydrogenases that were tested. Determination of N-terminal amino acid sequences of several bacterial and yeast lactate and mandelate dehydrogenases, together with the evidence from the immunological studies, confirmed and extended previous proposals that there are several major groups of such dehydrogenases: FMN dependent, membrane-bound L(+)-lactate and L(+)-mandelate dehydrogenases (M(r) = approx. 44,000) in bacteria, mitochondrial flavocytochrome b2 L(+)-lactate and L(+)-mandelate dehydrogenases (M(r) = approx. 59,000) in yeasts, FAD-dependent, membrane-bound D(-)-lactate and D(-)-mandelate dehydrogenases in bacteria, and soluble NAD-dependent D(-)-mandelate dehydrogenases in both bacteria and yeasts. PMID- 8360628 TI - Inhibition of phosphatidylcholine and chitin biosynthesis in Pyricularia oryzae, Botrytis fabae and Fusarium graminearum by edifenphos. AB - Colony growth of the fungi Pyricularia oryzae, Botrytis fabae and Fusarium graminearum was reduced by 50% (ED50) by edifenphos concentrations of 7, 25 and 190 microM respectively; the phosphatidylcholine (PC) content of biomass of P. oryzae, B. fabae, and F. graminearum harvested from fungicide-containing-cultures was reduced by 50% by 6, 95 and 350 microM-edifenphos respectively. By contrast, the activities of membrane-bound chitin synthase preparations isolated from the three fungi were approximately equally sensitive to edifenphos. A direct relationship was observed between PC contents of biomass grown in the presence of ediphenphos and in vivo rates of chitin synthesis (biomass incubated with [3H]GlcNAc in the absence of fungicide). Membrane-bound chitin synthase preparations from P. oryzae grown in medium containing 3 or 6 microM-edifenphos had, at the same fungicide concentration, a lower rate of in vivo chitin synthesis than preparations isolated from biomass grown in the absence of edifenphos. Membrane-bound chitin synthase preparations from P. oryzae grown in the presence and absence of 6 microM-edifenphos had the same Km values for the substrate (UDP-[14C]GlcNAc) but different Vmax values. The results suggest that chitin synthesis is inhibited directly by non-competitive inhibition of chitin synthase activity, and indirectly following inhibition of PC biosynthesis. P. oryzae is very sensitive to edifenphos because inhibition of PC biosynthesis occurs at very low fungicide concentrations, and therefore in this fungus inhibition of PC biosynthesis probably represents the primary mode of action of the fungicide. PMID- 8360629 TI - Purification and characterization of a serine proteinase from senescent sporophores of the commercial mushroom Agaricus bisporus. AB - A proteinase has been purified from the stipes of senescent sporophores of the mushroom Agaricus bisporus. The proteinase was inhibited by PMSF. It has a broad pH optimum, 6.5-11.5, and a narrow substrate specificity, requiring both a hydrophobic amino acid in the P1 position and a minimum peptide chain length. The apparent molecular mass of the proteinase was 27 kDa when determined by SDS-PAGE and 14.1 kDa when measured by gel filtration. The isoelectric point of the proteinase was 9.0. Polyclonal antibodies have been raised to the proteinase. The proteinase from A. bisporus has similar properties to, and 60% N-terminal sequence identity with, proteinase K from the fungus Tritirachium album. PMID- 8360630 TI - Distribution of anaerobic fungi in the digestive tract of cattle and their survival in faeces. AB - A most probable numbers procedure was used to enumerate populations of anaerobic fungi in the digesta and faeces of cattle. Anaerobic fungi were isolated from the rumen, omasum, abomasum, small intestine, caecum, large intestine and faeces. By determining the amount of digesta in each organ of the digestive tract, it was possible to estimate the total population of anaerobic fungi in cattle and make comparisons between populations in different organs. In addition to enumerating anaerobic fungi in freshly collected samples, they were quantified in digesta and faeces which had been dried at ambient temperature and stored in air for up to 9 months. These experiments showed that a higher proportion of the anaerobic fungi present in the hindgut and faeces were able to withstand desiccation than those present within the gastric and pre-gastric organs. Our results support the hypothesis that the life cycle of anaerobic fungi consists of three stages; the motile zoospore, the vegetative thallus and an aero-tolerant survival stage (cyst or resistant zoosporangium). PMID- 8360631 TI - Changes in levels of anti-dengue virus IgG subclasses in patients with disease of varying severity. AB - Extensive complement activation precedes onset of shock in dengue patients and complement "split products" C3a and C5a could be responsible, directly or indirectly, for the increased vascular permeability and disseminated intravascular coagulation which characterises dengue haemorrhagic fever (DHF) dengue shock syndrome (DSS). As IgG subclasses vary in their capacity to activate the classical complement pathway after combining with antigen, we have used an indirect enzyme linked immunosorbent assay (ELISA) to assess levels of IgG1-4 against each dengue serotype in acute and convalescent sera from patients with disease of varying severity. Acute phase sera from patients with dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS) contained higher levels of anti-dengue antibodies of the IgG1, complement fixing, subclass than similar sera from dengue fever (DF) patients. Conversely, acute phase sera from DHF and DSS patients contained lower levels of anti-dengue antibodies of the poor complement activating IgG2 subclass than acute phase sera from DF patients. No significant differences were detected between the levels of anti-dengue IgG3 and IgG4 antibody in acute phase sera from DF, DHF, and DSS patients. With the exception of levels of anti-dengue IgG2 antibody from DHF patients which were lower than those from DF and DSS patients, levels of anti-dengue IgG1, IgG2, IgG3, and IgG4 were similar in convalescent sera from all patients. These results provide a possible explanation for the activation of the serum complement system which precedes onset of shock in severe dengue infections. PMID- 8360632 TI - Antibody responses of children to the C-terminal peptide of the SH protein of respiratory syncytial virus and the immunological characterization of this protein. AB - The SH protein of RSV, a small integrated hydrophobic membrane protein, consists of 64 amino acid residues in the polypeptide of subgroup A and 65 amino acid residues in the polypeptide of subgroup B. We synthesized five peptides, representing the SH protein of each RSV subgroup comprised of the following amino acid residues: 2-16, 12-26, 35-49, 45-60, and for subgroup A, 51-64 and for subgroup B, 51-65. Peptides 2-16 and 51-64/65 represented the N-terminal and C terminal ends of the protein, respectively. In RIPA, under reducing conditions with mercaptoethanol, hyperimmune guinea pig (GP) serum against C-terminal peptide of the two subgroups precipitated the homologous 7.5 kDa and 21-30 kDa SH proteins. Under nonreducing conditions, the GP antipeptide sera precipitated all three SH proteins, suggesting that the 13-15 kDa protein exists as a dimer. The subgroup A 7.5 and 13-15 kDa proteins had apparent molecular weights about 1-2 kDa higher than the corresponding subgroup B proteins. The C-terminal peptides of subgroups A and B were used to characterize the immune response of 11 children, age 1 month to 1 year, with presumed primary RSV infection. Three of 4 children with subgroup A infection and 4 of 7 children with subgroup B infection developed homologous 4-fold rises in antibody to C-terminal peptide (aa 51-64/65) during convalescence. Except for one child with subgroup A and one child with subgroup B infection, the other 5 children developed heterologous rises also.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360633 TI - Aetiology of acute sporadic non-A, non-B viral hepatitis in India. AB - Non-A, non-B (NANB) hepatitis viruses are now classified as hepatitis E (enterically transmitted) and hepatitis C (parenterally transmitted). India experiences a large number of epidemics of the enteric disease every year. In addition, about 70% of the sporadic cases among adults are also due to NANB hepatitis. With the availability of an immunoblot assay for the detection of anti HEV-IgM and the polymerase chain reaction (PCR) for the detection of HCV-RNA, serum samples from epidemic and sporadic NANB patients were screened for these markers. We found that a large number of cases from the epidemics were HEV, though a few remained undiagnosed, while of the sporadic cases only a few could be diagnosed as HCV or HEV; a large proportion remained undiagnosed. PMID- 8360634 TI - Paramyxoviruses and Paget's disease. AB - Using the technique of in situ hybridisation, we extended our initial studies of the occurrence of canine distemper and measles virus in Paget's disease. Bone samples from untreated patients and patients treated with 3-amino hydroxypropylidene 1,1 bisphosphonate pamidronate (APD) were examined for canine distemper nucleocapsid (CDV-N), measles nucleocapsid (MV-N), respiratory syncytial virus fusion (RSV-F), and simian virus 5 haemoglutinin-neuraminidase (SV5-HN) sequences using 35S-labelled sense and antisense riboprobes. Only CDV-N mRNA was detected in osteoclasts, osteoblasts, and mononuclear cells. In untreated Paget's patients, 63.5% were found to have CDV sequences residing in bone cells, and 48.2% of those undergoing APD treatment were still found to have the viral sequences. RSV-F mRNA was only found in one patient. None of the other paramyxoviruses tested were detected. This study shows that CDV can infect a human host and may be an aetiological agent of Paget's disease of bone. PMID- 8360635 TI - Hepatitis B and hepatitis C among institutionalized psychiatric patients in Taiwan. AB - To investigate the seroprevalence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) in a psychiatric institution in Taiwan, where hepatitis B virus (HBV) is hyperendemic, a total of 780 patients with psychiatric disorders were studied. Enzyme-linked immunosorbent assays (ELISA) were used for testing HBsAg and anti-HCV. The prevalence of HBsAg was higher than that of anti-HCV among these patients (18.1% vs. 6.8%, P < 0.0001). The HBsAg carrier rate in these patients was consistent with that of the general population, with a trend for HBsAg carrier rate to be lower in the aged and in females. In contrast, the prevalence of anti-HCV was higher in these patients than in general population. Anti-HCV positivity was found more frequently in patients who had received blood transfusion previously (24% vs. 6.4%, P < 0.05). The majority (92%) of patients with positive anti-HCV did not have a history of apparent parenteral exposure. The prevalence of anti-HCV increased significantly with duration of the psychiatric disorder. The prevalence of anti-HCV also tended to increase with duration of hospitalization but without reaching statistical significance. These findings suggest that these institutionalized psychiatric patients contract hepatitis B, as does the general population in Taiwan, and they should be considered as a specific risk group for hepatitis C infection. PMID- 8360636 TI - Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus? AB - We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to anti-hepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3-4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G+A), indicating a mixture of wild-type and "e minus" variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity. PMID- 8360637 TI - Response of hemophilic patients to poliovirus vaccination: correlation with HIV serology and with immunological parameters. AB - Hemophilic patients may present immunological dysfunctions resulting from either human immunodeficiency virus (HIV) infection, or other factors like impure factor VIII concentrate and other viral infections. We evaluated prospectively the serologic response to polio vaccination of Israeli hemophilic patients who were vaccinated during an outbreak of poliomyelitis. Eighty-two hemophilic patients, 43 seronegative and 39 seropositive for human immunodeficiency virus (HIV), were vaccinated with enhanced inactivated poliovirus (eIPV). Titers of antibodies for poliovirus types 1-3 were determined before and 4 weeks after immunization. T helper and suppressor lymphocytes (T4 and T8), B and T lymphocyte mitogenic response, and natural killer cells were tested and correlated with the response to vaccination. Both groups responded to vaccination with increased titers of antibodies to the three viral types, 4 weeks after immunization. HIV-seronegative patients, however, exhibited higher titers than the HIV-seropositive group. The same pattern was found when 21 patients were tested 1 year after the exposure to eIPV. HIV seropositive patients were grouped according to their T4 count (between 16/microliter and 500/microliter). There was no statistically significant difference in the response of these different groups to vaccination. No correlation was found between the response to vaccination and other immune parameters. These results suggest that asymptomatic HIV-seropositive hemophilic patients respond well to eIPV, irrespective of their T4 count. PMID- 8360638 TI - Psychiatric comorbidity and treatment seeking. Sources of selection bias in the study of clinical populations. AB - Population studies have shown that the co-occurrence of psychiatric disorders increases the likelihood of treatment seeking. This leads to a biased estimation of the prevalence of comorbidity in clinical samples, and this overestimation can be attributed to two different sources of selection bias. Using data from a population survey of psychiatric disorders, in which 3258 residents of Edmonton, Alberta, Canada, were interviewed with the Diagnostic Interview Schedule, we assessed the extent of each of these two mechanisms. The first source of selection bias is the mathematical bias known as Berkson's bias and arises from the fact that an individual affected with two psychiatric disorders can seek treatment for either one or the other of these disorders. The second source of selection bias is clinical and results from the changed probability of seeking a treatment for a specific disorder because of the existence of a comorbid disorder. PMID- 8360639 TI - A comprehensive review of cyclothymic disorder. AB - Chronic affective disorders have generated much interest during the past decade due to increasing recognition of their clinical importance and because of controversy about their appropriate classification and treatment. The purpose of this paper was to review cyclothymic disorder. This review will include historical concepts, clinical phenomenology, family history, biological studies, and treatment of cyclothymia. In addition, the relationship of cyclothymia to other psychiatric disorders, such as bipolar, dysthymic, and personality disorders, is examined. The results suggest that some forms of cyclothymia are strongly associated with bipolar disorder, but that the condition is clinically heterogeneous. The problems of existing research in this area and future directions for research are also discussed. PMID- 8360640 TI - Perception of facial emotion in schizophrenic and right brain-damaged patients. AB - Deficits in the perception of facial emotion have been demonstrated in patients with right-sided brain damage (RBD) and schizophrenia (SZ). Furthermore, recent speculations have implicated right-hemisphere dysfunction in Type II schizophrenics, especially those with a preponderance of "negative symptoms" and flat affect. The performance of SZ, RBD, and normal control subjects was compared on measures assessing facial emotional perception. Both identification and discrimination paradigms were used, with positive/pleasant and negative/unpleasant emotions. To examine the effects of visuospatial and facial processing on facial emotion tasks, the Visual Matrices Test and the Benton Facial Recognition Test were administered. On both facial emotion tests, SZ and RBD patients were significantly impaired relative to normal subjects, but not different from each other. The SZ and RBD patients were also impaired on the matrices and facial recognition tests. When the effects of the matrices and neutral face recognition tests were statistically controlled, significant group differences remained for the identification task but not for the discrimination task. Thus, methodologies are presented for the neuropsychological study of facial emotional perception, and some support is provided for the notion that negative-symptom schizophrenia is associated with right hemisphere dysfunction. PMID- 8360641 TI - Treatment response of borderline inpatients. A growth curve analysis. AB - This study examined the course of 40 hospitalized female borderline personality disorder patients over 25 weeks of inpatient treatment. Course was measured through weekly administration of the SCL-90-R. Level of identity and interpersonal problems, hypothesized by Kernberg to be at the center of the borderline patient's pathology, were found to be powerful predictors of treatment course. Patients with the most severe identity and interpersonal problems reported more symptoms throughout treatment and increasing symptom levels over time. This was very different from patients with the lowest level of identity and interpersonal problems, who reported fewer symptoms overall and decreasing symptoms over time. PMID- 8360642 TI - Perinatal substance abusers. Psychological and social characteristics. AB - Forty perinatal substance abusers were administered multiple psychosocial, addiction, and psychological measures before beginning treatment. Results indicate that these patients are limited intellectually, educationally, financially, and emotionally. Psychiatric comorbidity was high, with 45% having non-substance abuse axis I diagnoses and 75% having confirmed (by two or more tests) axis II pathology. The most frequently identified axis I disorders were depression and anxiety. The most frequently detected personality disorders were antisocial, borderline, paranoid, and dependent. The average IQ was 87 (low average range) and nearly one third of the sample were found to be somewhat impaired intellectually. These data suggest that treatment programs must take psychological characteristics into account if they are going to succeed in helping these women achieve and maintain abstinence. PMID- 8360643 TI - Long-term outcome of treated schizophrenia in a Nigerian cohort. Retrospective analysis of 7-year follow-ups. AB - Consecutive case records of 142 patients (55 males and 87 females) who fulfilled stringent criteria for schizophrenia, and attended the psychiatric facilities at the Ibadan teaching hospital for at least 7 consecutive years were studied in detail in order to determine outcome in a period of follow-up that ranged from 7 to 26 years (mean +/- SD, 13.3 +/- 4.6 years). A unique history of stability of staff and research record keeping, as well as the fact that relatives frequently accompany patients to hospital, enhanced the reliability and validity of documents. Using outcome criteria that included the presence of positive and negative symptoms of schizophrenia and social adjustment in the past 12 months, it was found that 72 (50.7%) patients were in the good outcome group, while 34 (23.9%) and 36 (25.4%) had moderate and poor outcome, respectively. The social and clinical characteristics of the patients were similar to those of participants in World Health Organization prospective studies in this country. Whereas there was a nonsignificant trend for more females to be without psychotic symptoms, the males performed significantly better in social adjustment outcome measures. In contrast with reports from the Western world, patients with acute onset and episodic course were a common feature of the cohort. The results support previous reports indicating fairly good outcome of schizophrenia in developing countries. PMID- 8360644 TI - Delusional mania: what is a mood-incongruent psychotic feature? PMID- 8360645 TI - Lithium neurotoxicity at therapeutic levels in an AIDS patient. PMID- 8360646 TI - Abuse potential of carbamazepine. PMID- 8360647 TI - A putaminal lesion in an adolescent with obsessive-compulsive disorder and atypical anorexia nervosa. PMID- 8360648 TI - War and posttraumatic stress disorder: the question of social context. PMID- 8360649 TI - How to run a brain bank. PMID- 8360650 TI - The need of a consensus for brain banking. PMID- 8360651 TI - A brain bank in a neuropathology laboratory (with some emphasis on diagnostic criteria). AB - The Brain Bank of La Salpetriere Hospital (Paris) is implanted in a neuropathology laboratory. It is multipurpose, prospective, and "free of charge" for the users. Protocols are prospectively established, in collaboration with the neuroscientists. One of our major difficulties in the collection of cases concerns presently the controls: the neurological status of patients coming from Neurology departments has usually been correctly assessed but those patients are bad controls. The normality of the neurological status of patients dying in other departments is difficult to assess retrospectively. A general autopsy is performed in each case. Several systematic sampling and fixation procedures are currently in use; their pros and cons are discussed. The main safety problem we are confronted with is the risk of HIV and Jakob-Creutzfeldt transmission. We try to standardize our diagnostic procedures; criteria used in Alzheimer's disease, Parkinson's disease, Huntington's chorea are briefly reviewed. We plan, in the future, to standardize our procedures for control cases. The Brain Bank has had a very positive impact on the way this neuropathology laboratory works: it introduced new techniques; on the other hand, the adequate processing and diagnosis of the samples was, in many aspects, simplified by the collaboration with the neuropathology department. The demand for human brain samples is steadily increasing in Neuroscience, for at least 2 reasons: 1. some diseases are specifically human and lack adequate animal models (Alzheimer's disease, multisystem atrophy), or animal models may appear irrelevant in some aspects (multiple sclerosis) or finally, results obtained in animal models may have to be confronted with human pathology (AIDS ...) 2. many aspects of human neuroanatomy can not be extrapolated from animal data There are many ways of organizing a brain bank and no golden standard (Swaab et al., 1989): the neuroscientist himself may collect the samples in a given pathology or the neuropathologists may modify their practice to provide adequate samples to the neuroscientists. When the neuroscientist himself collects his own samples, he obviously proceeds more rapidly. However, he is confronted with the difficult problem of the controls, which require both a clinical follow-up and a pathological check up of the tissues, both of which may be difficult to obtain in a research unit. In our opinion, the neuropathologists are the natural "brain bankers": they are indeed naturally "rich", their job being precisely to collect human samples, in connection with the clinicians.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360652 TI - Brain banks and research in neurochemistry. AB - The increasing demand to brain banks for specimens that are properly prepared for research in neurochemistry has stimulated interest in the drawing up of suitable protocols. The purpose of this chapter is twofold: (1) to describe the various strategies that are currently applied in different brain banks and (2) to point out the main neurochemical requirements in order to reach a consensus with the brain bank about the more suitable protocol in each case. In recent years, some brain banks have acquired the necessary equipment and now have access to neurochemical expertise. Their experience will be very helpful in defining the new procedures to be used at each stage of brain tissue banking and will permit the development of research projects in this discipline. PMID- 8360653 TI - Brain banking for immunocytochemistry and autoradiography. AB - The aim of a human brain bank is to establish groups of matched brains (normal control versus pathological groups) for studying human diseases of the nervous system. This bank is obtained by means of autopsy performed with a very short post-mortem delay and from clinically and neuropathologically well-documented patients. According to research protocols, two types of brain tissue storage are performed: fixed tissue or frozen tissue. Brain dissection procedures are performed according to precise anatomical boundaries of each brain region. This paper will center on the questions raised by brain banking in relation to histological and immunocytochemical studies and to biochemistry and autoradiography of binding sites. The lack of neuroanatomical data of the human brain leads us to compare anatomical results obtained in animals to that of the human. Moreover, it is clear that human brains present numerous interindividual differences (Kopp et al., 1977; Jack et al., 1989). Therefore, investigations of the human brain should be made on a large series of brains indicating the necessity of a well-documented brain bank of tissue from normal controls and patients. PMID- 8360654 TI - The Netherlands brain bank--a clinico-pathological link in aging and dementia research. AB - The number of sophisticated neurobiological techniques which can be applied on human brain has rapidly increased and causes an increased demand for post-mortem human brain tissue for research purposes. Brain banks, which collect post-mortem tissue from patients who suffered from neurological and psychiatric disorders, have become an important link between clinicians, scientists and neuropathologists involved in aging and dementia research. Due to the large variability of the material, there are many drawbacks in the use of post-mortem brains. Therefore, collecting human brain tissue for research should include matching for several factors, both ante-mortem and post-mortem. Some of the most important ante-mortem factors include age, sex, agonal state, seasonal alterations, circadian variation and clock time of death. The post-mortem factors which should be matched for include the post-mortem delay, fixation and storage time and lateralization. The material and data on aging and dementia, collected by the Netherlands Brain Bank in the past six years will serve in the present paper to illustrate the wide variety of potentialities and pitfalls in the use of post-mortem human brain tissue. Brain Bank organizations for various neurological diseases form at present an important clinico-pathological link in aging and dementia research and the availability of post-mortem human brain tissue makes it possible to investigate those diseases for which no animal model is available. In order to provide research groups with post-mortem brain tissue from Alzheimer's disease (AD) patients and controls, a brain bank was established by the end of 1985 in The Netherlands Institute for Brain Research. This brain bank is based upon research projects submitted in advance, specifying a variety of requirements such as: total number of brains needed, kind of fixation, agonal state, post mortem delay, exact anatomical boundaries of the brain region, kind of fixation and other treatment requirements of the tissue. This Brain Bank has got two unique features: 1. Human brain tissue is obtained by means of rapid autopsies with a very short post-mortem delay, ranging between 2-4 hour. 2. Fresh brain dissection procedure is used, which is a difficult regime to establish, requiring qualified staff at inconvenient times. This dissection procedure is necessary for the immediate use of fresh tissue and advantageous in increasing the range of morphological, neurochemical, immunocytochemical, metabolic and other procedures which can be applied to tissues fixed in a different way or rapidly frozen brain tissue free of freezing artifacts. PMID- 8360655 TI - Organization and research applications of the U.K. Multiple Sclerosis Society Tissue Bank. AB - The Multiple Sclerosis Society Tissue Bank contains post-mortem central nervous system tissue from over 100 clinically and neuropathologically well-documented multiple sclerosis (MS) cases, and from normal control subjects. This bank is a resource centre which provides histologically screened snap-frozen material for immunological, neurochemical and nucleic acid studies in our own and other MS laboratories in Europe and the USA. In addition to immunopathological studies, Tissue Bank material has been used to investigate changes in CNS-specific proteins and lipids in MS plaques and responses of oligodendrocytes and astrocytes to the inflammatory demyelinating process. MS lesions detected in unfixed post-mortem brain and spinal cord by magnetic resonance imaging techniques prior to dissection have been characterized histologically and biochemically. A computer database on Tissue Bank post-mortem cases has been established to link clinical, pathological and scientific aspects of MS research. PMID- 8360656 TI - Parkinson's Disease Society Brain Bank, London: overview and research. AB - The UK Parkinson's Disease Society Brain Bank receives tissue from patients with Parkinson's disease and a variety of different movement disorders. Half of the brain is used for full neuropathological examination prior to allocation for specific research projects. Clinical misdiagnosis occurs in a significant proportion of cases and clinico-pathological correlation provides valuable information for disease recognition. With the expanding number of other specialist brain banks there is a need for agreement on diagnostic criteria. Furthermore, awareness of different methods of tissue handling is essential. PMID- 8360657 TI - The development of a brain bank. AB - The methods used in developing a brain bank are described. The techniques for encouraging brain donation and the precautions to be used when dealing with medical examiner cases are outlined. Simplifying the donation process by the pathologist in order to gain his cooperation is essential. The importance of keeping an open telephone link available at all hours of the day and night and the need to solicit the donating families' cooperation in seeking clinical records is emphasized. Detailed neuropathological examination of every brain is essential for diagnostic purposes. Recent techniques to improve the qualify of postmortem brain tissue for molecular genetic studies are described. PMID- 8360658 TI - Pathological assessment of movement disorders: requirements for documentation in brain banks. AB - The general methodological requirements and principal morphologic hallmarks for the post mortem assessment of the major types of movement disorders are critically reviewed. These data may enable Brain Banks to classify movement disorders according to current clinicopathological diagnostic criteria. Comprehensive clinical assessment and accurate neuropathological examination using adequate methods are required for collection of and research on tissues from patients with movement disorders. PMID- 8360659 TI - Parkinson's Disease Brain Bank in Paris: an evolutive bank responding to the exigencies of new neurochemical methodologies. AB - The purpose of a brain bank is to collect specimens in order to investigate human brain and pathologies of the central nervous system. The organization of the brain bank in Paris, devoted to the study of Parkinson's disease, is described, with it's evolutions with years, to respond to the exigencies of the new neurochemical methodologies. PMID- 8360660 TI - The interest of the neurological tissue preservation for the investigation of sudden infant death syndrome. AB - Sudden infant death syndrome (SIDS) is the main cause of post-natal infant mortality in developed countries with an incidence rate ranging from 1.5 to 2:1000 live births. Brainstem dysfunction of circuits which control respiration and cardiovascular stability may be involved in SIDS. Combined neuropathological and biochemical studies could elucidate some of these aspects. The relationships of these deaths to medico-legal problems could explain the scarce availability of these tissues. The need for a central SIDS tissue bank is emphasized and a protocol for the collection of CNS tissue is proposed. A detailed neuropathological study using this protocol allowed us to recognize pathological features in the CNS of 9 SIDS cases. Some features were related to the maturation of CNS, and others to possible infections. Gliosis was a common finding in most cases. The present state of SIDS investigation and results are also discussed. PMID- 8360661 TI - Amyotrophic lateral sclerosis brain banking: a proposal to standardize protocols and neuropathological diagnostic criteria. AB - Motorneurons which are primarily affected in ALS cannot be sampled during life. Morphological, biochemical, ultrastructural and molecular investigations can be only performed on post-mortem material. No animal model reproduce adequately ALS. All these features and the low ALS incidence and the absence of definite clusters stress the need for brain banking in Europe. We present the protocol which is followed in our centers. The clinical information is supplied by neurologists in order to provide clinical data necessary for an accurate interpretation of pathological features. Initial symptomathology, duration and type of ALS, cause of death and a simple disability scale shortly before death are included. CNS relevant samples stained with H-E, luxol fast blue, the Marchi impregnation technique and immunostained with ubiquitin, are used for diagnosis. Samples for Golgi impregnation and immunohistochemistry are also obtained and the remaining tissue is frozen. Classical criteria for pathological diagnosis include: neurogenic changes in muscles, loss of motorneurons and degeneration of corticospinal tracts. We propose new diagnostic criteria based only on CNS examination. Muscle tissue is not always available and other classical criteria could be absent in rapid evolution or early death cases. Our criteria includes: a) Major criteria: loss or degeneration (chromatolysis, basophilia or neuronophagia) of motorneurons in brainstem and/or spinal cord, degeneration of corticospinal tracts. b) Minor criteria: axonal spheroids, Bunina bodies, ubiquitin-immunoreactives bodies. Criteria necessary for the pathological diagnosis are discussed and the need to quantify neuronal loss in relation to age matched controls is stressed. PMID- 8360662 TI - Changes in the myelinated axons of femoral nerve in amyotrophic lateral sclerosis. AB - Myelinated fibres in femoral nerves removed from amyotrophic lateral sclerosis (ALS) cases at post mortem were compared with age matched controls. A technique for processing whole transverse sections of the nerves for osmication and subsequent morphometric analysis is described. Although areas depleted in myelinated fibres were seen in the nerves from the ALS group, no statistically significant difference was shown due to wide variations in the controls. However, the ALS nerves showed a degree of disruption in the myelin which was not apparent in the controls. The most obvious effect was widespread "wrinkling" of the myelin in both large and small fibres from the ALS nerves. This phenomenon is the initial stage of a process which eventually results in uneven myelin thickness and nodal swellings and finally myelin ovoids and balls. We illustrate the steps in the progression of this degeneration with teased nerve studies and electron microscopy and propose that there are qualitative changes in the myelin of peripheral nerve in ALS. It seems likely that these are secondary effects resulting from axonal degeneration caused by deterioration and loss of anterior horn cells in the spinal cord. PMID- 8360663 TI - How to run a brain bank: potentials and pitfalls in the use of human post-mortem brain material in research. AB - Brain banks for neurological diseases serve as a link between the clinician, the neuropathologist and the basic scientist who require brain tissue samples from patients who have undergone a thorough clinical investigation and whose brains have been subjected to detailed neuropathological analysis. In order to provide research groups with post-mortem brain tissue from patients who show clinical signs of dementia such as Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT), vascular dementia including multi-infarct dementia (MID) and mixed dementia, a brain bank was established at Huddinge University Hospital at the end of 1988. The brain bank provides either rapidly or slowly frozen tissue samples, tissue samples fixed in formalin (short/long fixation time), cerebrospinal fluid (CSF), and blood samples. Average postmortem times are from 3-47 hours. The information available on the cases includes the clinical diagnosis, the premortem clinical investigation with behavioral observations, psychometric and neuropsychological test data, premortem medication, cause of death, agonal state, pH in brain and CSF, and the general anatomic and neuropathologic assessments leading to the final diagnosis. PMID- 8360664 TI - How to run a brain bank. A report from the Austro-German brain bank. AB - The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the concept and practice of our brain bank. Both brain tissue and information are handled by standardized procedures and flow in parallel from pathology to neuropathology and neurochemistry. Data concerning brain material are updated with clinical information gained by standardized procedures. PMID- 8360665 TI - Human neuro-specimen banking 1961-1992. The National Neurological Research Specimen Bank (a donor program of pre- and post-mortem tissues and cerebrospinal fluid/blood; and a collection of cryopreserved human neurological specimens for neuroscientists). AB - The National Neurological Research Specimen Bank (The Bank) was established in 1961 to provide a vital service to neuroscientists. Our purpose is to support medical research which seeks the etiopathogenesis for devastating neurological disorders with no known cause, treatment or precise animal model. It serves as a bridge between the neurology clinician who diagnoses and cares for patients with incurable disease and the basic scientist who has need for specimens to find their etiopathogenesis. In the long run this service should advance neurologic diagnoses and serve as the basis for designing treatment. The Bank has grown to be the largest, most diverse neurological specimen bank of its kind in the world. It is a type of "tissue bank" where donor members "will" their central nervous system tissues to science. Then we collect, photograph, seal in air tight bags, quick freeze, cryogenically store and distribute on request the donated tissue to research scientists around the world. All tissue diagnoses are confirmed by clinical records and neuropathologic examination; further histology is conducted on request. In addition to brain and spinal cord tissues, the Bank has samples of other tissues. There are also samples of pre- and post-mortem CSF and sera from normal individuals and patients with various neurological disorders, especially serial specimens on multiple sclerosis patients and HIV-1 seropositive and at risk individuals. This paper outlines the global operations of our human brain bank, based on protocols developed and used by the authors. These operations include donor solicitation, tissue acquisition and documentation, tissue processing and storage, specimen dissemination to users, outcome assessment of banking, quality control, cost of our operation, table of organization and the future. PMID- 8360666 TI - How to run a "brain bank"? Clinical and institutional requirements for "brain banking". AB - "Brain Banking" or prospective sampling of tissues relevant to the study of neurological disease is a complex task which needs organization at various levels of operation such as the establishment of a donor system, recruitment of clinical assessment centres, establishment of standardized assessment protocols, the inauguration of logistic structures for brain removal and transport to the bank, proper storage of patient data and tissues, histological verification of the disease and availability of tissue and clinical data to researchers. This effort certainly promises to bear fruit since there is a striking lack of precise prospective studies into etiology and pathogenesis in most neurological diseases especially in the field of the neurodegenerative diseases. PMID- 8360667 TI - The contemporary AIDS database and brain bank--lessons from the past. AB - This paper addresses the issues in establishing a contemporary AIDS Brain Bank with a Database. It draws comparisons from the past when a similar approach was made towards the understanding of mental illness and its treatment. The aim of the Brain Bank is to provide a comprehensive range of neuropathologically characterised tissues from the nervous system to researchers and scientists as a resource for research. The aim of the Database is to provide the up-to-date clinical and pathological information relating to the material supplied by the Brain Bank. The paper describes the mechanics of establishing the Database, the importance of efficiency as well as discussing the sensitive issues that need to be addressed when designing and AIDS Database and Brain Bank. PMID- 8360668 TI - Brain banks and non nervous tissues. AB - Nervous system diseases may not be confined to neural tissue, but also affect other organs. These organs could be involved indirectly or could be simultaneously affected by the same pathological process. A brain bank (BB) should also guarantee the storage of specific organs primarily or secondary affected other than nervous system. Tissues from patients with primary nervous system diseases without or with unknown systemic involvement should also be stored. Samples stored will be identified and registered in a BB database for an accurate distribution and utilization of the material. To guarantee the best quality of the material stored, several techniques for the collection and preservation (cryopreservation, chemical fixation and microwave irradiation) and tissue management are described. PMID- 8360669 TI - Biliverdin reductase is heat resistant and coexpressed with constitutive and heat shock forms of heme oxygenase in brain. AB - Two heme oxygenase (HO) isozymes--HO-1, which is a heat shock protein (HSP32), and HO-2--catalyze the isomer-specific production of biliverdin IX alpha and carbon monoxide. The latter has the potential of functioning as a neurotransmitter, whereas the reduced form of biliverdin, bilirubin, has potent antioxidant activity. Formation of bilirubin is catalyzed by biliverdin reductase (BVR). The reductase is a unique enzyme in being dual pyridine nucleotide and dual pH dependent. Here, we show that the reductase is resistant to thermal stress at both the protein and message level. We further demonstrate that the reductase is coexpressed in cells that display HO-1 and/or HO-2 under normal conditions, as well as in regions and cell types that have the potential to express heat shock-inducible HO-1 protein. Exposure of male rats to 42 degrees C for 20 min did not decrease brain BVR activity, but caused a slight increase in NADPH- and NADH-dependent activities at 1 and 6 h following hyperthermia. High levels of the approximately 1.5-kb BVR mRNA were detected in control brain; it too displayed thermal tolerance. Similarly, the pattern of multiplicity of net charge variants of the enzyme purified from brain of heat-shocked rats did not differ from the control pattern. Immunochemical localization of BVR protein in normal brain correlated well with the presence of HO-1 and/or HO-2 throughout the forebrain, diencephalon, cerebellum, and brainstem regions. There were select neuronal and nonneuronal cells in the substantia nigra and cerebellum that did express the reductase under normal conditions, wherein no HO isozymes could be detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360670 TI - Nerve growth factor stimulates the production of inositol 1,3,4- and 1,4,5 trisphosphate and inositol 1,3,4,5-tetrakisphosphate in PC12 cells. AB - In PC12 cells, preincubated with [3H]inositol, nerve growth factor (NGF) stimulated an approximately 100% increase in the levels of [3H]inositol 1,3,4 trisphosphate ([3H]-Ins(1,3,4)P3], [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3], and [3H]inositol 1,3,4,5-tetrakisphosphate ([3H]Ins(1,3,4,5)P4] as early as 5-15 s after addition of NGF. This NGF-mediated response was apparent only when the cells had been cultured in the absence of fetal bovine serum (FBS). PC12 cells cultured in FBS-containing medium did not display NGF-mediated increases in [3H]Ins(1,3,4)P3, [3H]Ins(1,4,5)P3, and [3H]Ins(1,3,4,5)P4 levels. Using cells cultured in the absence of FBS, epidermal growth factor (EGF) and fibroblast growth factor also stimulated production of [3H]Ins(1,3,4)P3, [3H]Ins(1,4,5)P3, and [3H]Ins(1,3,4,5)P4. Lavendustin A, a tyrosine kinase inhibitor, inhibited both the EGF- and NGF-stimulated increases in the levels of these tritiated inositol phosphates. These results suggest that NGF stimulates the production of Ins(1,3,4)P3, Ins(1,4,5)P3, and Ins(1,3,4,5)P4 and that this response is dependent on tyrosine kinase activity. Furthermore, although the production of Ins(1,3,4)P3, Ins(1,4,5)P3, and Ins(1,3,4,5)P4 may be a common response to factors stimulating neuronal differentiation, it is not sufficient for stimulation of neuronal differentiation. PMID- 8360671 TI - Muscarine receptors regulating electrically evoked release of acetylcholine in hippocampus are linked to pertussis toxin-sensitive G proteins but not to adenylate cyclase. AB - [3H]Acetylcholine release elicited with 360 pulses/3 Hz from slices of rabbit hippocampus is facilitated in the presence of the muscarine (M) receptor antagonist atropine (indicating the existence of autoinhibition) and diminished by the M receptor agonists carbachol and oxotremorine. N-Ethylmaleimide (30 microM) and pertussis toxin (8 micrograms/ml) counteracted antagonist-induced facilitation and agonist-induced inhibition of release, suggesting that a pertussis toxin-sensitive GTP-binding protein is involved in the chain of events mediating activation of M receptors to inhibition of release. Neither 8-bromo cyclic AMP (300 microM), a membrane analogue of cyclic AMP, nor rolipram (10 microM), a phosphodiesterase inhibitor, affected electrically evoked release of [3H]acetylcholine. They also did not influence the oxotremorine-induced inhibition of transmitter release. In conclusion, no evidence was found for the assumption that activation of M autoreceptors is linked to inhibition of adenylate cyclase. PMID- 8360672 TI - Homologous desensitization of serotonin 5-HT2 receptor-stimulated intracellular calcium mobilization in C6BU-1 glioma cells via a mechanism involving a calmodulin pathway. AB - Serotonin 5-HT2 receptor-mediated intracellular Ca2+ mobilization was investigated in rat glioma C6BU-1 cells. The receptors became desensitized after previous exposure to 5-HT in a time- and concentration-dependent manner. The desensitization of 5-HT2 receptor-mediated intracellular signaling appeared to be homologous because previous exposure to 5-HT did not alter the response to other transmitters such as thrombin or isoproterenol and because previous exposure to thrombin or isoproterenol did not diminish the response to 5-HT. The desensitization induced by pretreatment with 5-HT was potently prevented by the naphthalenesulfonamide derivative W-7, a calmodulin antagonist, when it was cosupplied with 5-HT. Furthermore, the preventive effect of W-7 was greater than that of W-5, a weak analogue of W-7, and than that of H-7, a nonselective inhibitor of protein kinases. These results suggest that 5-HT2 receptor-mediated Ca2+ mobilization can be desensitized homologously after prolonged exposure to 5 HT in a calmodulin-dependent manner in rat glioma C6BU-1 cells. PMID- 8360673 TI - Effect of an n-3 fatty acid-deficient diet on the adenosine-dependent melatonin release in cultured rat pineal. AB - We studied the effect of a diet deficient in n-3 fatty acids on the adenosine dependent melatonin release from cultured rat pineal gland after stimulation by 5'-N-ethylcarboxamidoadenosine (NECA), an A2 adenosine agonist. Experiments were conducted with 2-month-old rats raised on semipurified diets containing either peanut oil (n-3 deficients) or peanut plus rapeseed oil (controls). The proportion of docosahexaenoic acid (22:6 n-3) in the pineal total lipid fraction and in phosphatidylcholine and phosphatidylethanolamine was significantly decreased in n-3-deficient rats. This was compensated for partially by an increase in 22:4 n-6 and 22:5 n-6 levels. The activity of the cultured rat pineal, in terms of cyclic AMP content and N-acetylserotonin and melatonin release in the medium, was lower after stimulation by 10(-5) mol/L NECA in the group fed peanut oil than in the group fed peanut plus rapeseed oil. The increased ratio of n-6/n-3 fatty acids in pineal total lipids and the major glycerophospholipids (phosphatidylcholine and phosphatidylethanolamine) may have an important influence on the rat pineal responses. The results are discussed in the context of changes in membrane-bound proteins, including enzymes and/or receptors involved in the rat pineal gland function. PMID- 8360674 TI - High and low molecular weight tau proteins are differentially expressed from a single gene. AB - Both high and low molecular weight (HMW and LMW) tau proteins are expressed in the immature and adult mouse spinal cord. Northern blot analysis, performed with probes complementary to domains common and uncommon to the LMW and HMW entities, suggested that HMW tau proteins found in the immature mouse spinal cord are not translated from the single transcript of 6 kb expressed at these stages, but are transported within this nervous structure by axons arising in the periphery. In contrast, another minor transcript of 8 kb was detected in the adult mouse spinal cord by a HMW tau specific probe, suggesting that a small fraction of the HMW tau forms present in adulthood are translated within mouse spinal cord neurons. LMW spinal cord tau forms are encoded by mRNAs of 6 kb that contain three and four homologous repeats at immature and mature stages, respectively, whereas adult HMW entities contain four repeats. PCR analysis performed with mouse genomic DNA also showed that the nonhomologous region specific for HMW tau is a single exon. Southern blot and gene mapping showed that the same gene, located on the murine chromosome 11, encodes all the LMW and HMW tau variants. All these tau forms, therefore, are produced by an alternative splicing mechanism that is neuron specific and developmentally regulated. PMID- 8360675 TI - Molecular cloning of two additional members of the neural visinin-like Ca(2+) binding protein gene family. AB - We have isolated a rat cDNA clone encoding a neural visinin-like Ca(2+)-binding protein (NVP), which we designate NVP-1. To identify additional molecular forms of NVP, a rat brain cDNA library was screened for their presence using an NVP-1 cDNA probe under low-stringency hybridization conditions. Two types of cDNA clones encoding structurally related proteins, designated NVP-2 and NVP-3, have been isolated. The deduced amino acid sequences of NVP-2 and NVP-3 are 89.0% and 68.6% identical to that of NVP-1, respectively, and contain consensus sequences for EF-hand Ca(2+)-binding sites. Northern blot analysis shows that NVP-1, NVP-2, and NVP-3 mRNAs are most highly expressed in brain and are differentially expressed in various regions of rat brain. These results suggest that NVP-2 and NVP-3 are additional members of the NVP gene family. PMID- 8360676 TI - Basic fibroblast growth factor-induced increase in zif/268 and c-fos mRNA levels is Ca2+ dependent in primary cultures of hippocampal neurons. AB - Basic fibroblast growth factor (bFGF) is present in the developing rat brain and has been shown to provide critical trophic support for hippocampal neurons in culture. The influence of bFGF on the expression of mRNAs encoding the transcription factors zif/268 and c-fos was studied in primary cultures of hippocampal neurons (derived from rat embryos) using reverse transcription coupled PCR. In these cultures grown for 3 days in the absence of serum, bFGF causes a dramatic and transient increase in the levels of zif/268 and c-fos, within 15 and 30 min, respectively. A similar induction of these two early genes occurs following activation of protein kinase C (PKC). The bFGF-induced activation persists after PKC desensitization but is inhibited by chelation of intracellular Ca2+. These results suggest that in primary cultures of hippocampal neurons, bFGF induces the expression of immediate early genes through a pathway that requires Ca2+ mobilization. PMID- 8360677 TI - Identification and characterization of endothelin receptor subtype B in rat retina. AB - The presence of immunoreactive (IR) endothelin (ET)-1 and ET-1 receptors in rat retina has been studied by radioimmunoassay and receptor assay, respectively. The specific binding of 125I-ET-1 to rat retinal particulate preparations was saturable. Apparent equilibrium conditions were established within 120-140 min. Scatchard analysis of binding data indicated a single class of high-affinity binding sites with a KD of 35 +/- 11 pM and a Bmax of 168 +/- 60 fmol/mg of protein. 125I-ET-1 binding to retinal particulate preparations was not inhibited by 1 microM concentrations of somatostatin, atrial natriuretic factor, brain natriuretic peptide, thyroid-stimulating hormone, growth hormone, or insulin. The three endothelin isoforms, ET-1, -2, and -3, had similar affinity for the receptor. Cross-linking of 125I-ET-1 to retinal particulate preparations with disuccinimidyl suberate resulted in the labeling of two bands with apparent molecular masses of 52 and 34 kDa. We have established a highly sensitive and specific radioimmunoassay for ET-1. The concentration of IR-ET-1 in rat retina was 35 +/- 10 fmol/g wet weight. The demonstration of specific high-affinity ETB receptors and the presence of IR-ET-1 suggest that the peptide may act as a neurotransmitter or neuromodulator in the retina. PMID- 8360678 TI - Subunit association and glycosylation of acetylcholinesterase from monkey brain. AB - Cercopithecus monkey brain acetylcholinesterase (AChE; EC 3.1.1.7) consists of about 15% hydrophilic, salt-soluble enzyme and 83% amphiphilic, detergent-soluble enzyme. Sucrose density gradient centrifugation showed that hydrophilic, salt soluble AChE was composed of about 85% tetramer (10.3S) and 15% monomer (3.3S). In amphiphilic, detergent-soluble AChE, 85% tetramer (9.7S), 10% dimer (5.7S), and 5% monomer (3.2S) were seen. The enzyme is N-glycosylated, and no O-linked carbohydrate could be detected. Use of two monoclonal antibodies, one directed against the catalytic subunit and the other against the hydrophobic anchor, gave new insights into the subunit assembly of brain AChE. It is shown that in tetrameric AChE, not all of the subunits are disulfide-bonded and that two populations of tetramers exist, one carrying one and the other carrying two hydrophobic anchors. PMID- 8360680 TI - Inhibition of succinate dehydrogenase by malonic acid produces an "excitotoxic" lesion in rat striatum. AB - Excitotoxicity and defects in neuronal energy metabolism have both been implicated in the pathogenesis of neurodegenerative disease. These two mechanisms may be linked through the NMDA receptor, activation of which is dependent on neuronal membrane potential. Because the ability to maintain membrane potential is dependent on neuronal energy metabolism, bioenergetic defects may affect NMDA receptor-mediated excitotoxicity. We now report that reversible inhibition of succinate dehydrogenase (SDH), an enzyme central to both the tricarboxylic acid cycle and the electron transport chain, produces an "excitotoxic" lesion in rat striatum that can be blocked by the NMDA antagonist MK-801. Male Sprague-Dawley rats received intrastriatal stereotaxic injections of the SDH inhibitor malonic acid (1 or 2 mumol) in combination with intraperitoneal injections of vehicle or MK-801 (5 mg/kg) 30 min before and 210 min after malonic acid. Animals were killed 72 h after surgery, and brains were processed for histology, cytochrome oxidase activity, and [3H]MK-801 and [3H]AMPA autoradiography. The higher dose of malonic acid (2 mumol) produced large lesions that were markedly attenuated by treatment with MK-801 (28.1 +/- 3.6 vs. 4.7 +/- 2.6 mm3; p < 0.001). [3H]MK-801 and [3H]AMPA binding were reduced in the lesions by 60 and 63%, respectively. One micromole of malonic acid produced smaller lesions that were almost completely blocked by MK-801 treatment (9.6 +/- 1.3 vs. 0.06 +/- 0.04 mm3; p < 0.0001). The toxic effects of malonic acid were due specifically to inhibition of SDH inasmuch as coinjection of a threefold excess of succinate with the malonic acid blocked the striatal lesions (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360679 TI - Neurofilament proteins are synthesized in nerve endings from squid brain. AB - It is generally believed that the proteins of the nerve endings are synthesized on perikaryal polysomes and are eventually delivered to the presynaptic domain by axoplasmic flow. At variance with this view, we have reported previously that a synaptosomal fraction from squid brain actively synthesizes proteins whose electrophoretic profile differs substantially from that of the proteins made in nerve cell bodies, axons, or glial cells, i.e., by the possible contaminants of the synaptosomal fraction. Using western analyses and immunoabsorption methods, we report now that (a) the translation products of the squid synaptosomal fraction include neurofilament (NF) proteins and (b) the electrophoretic pattern of the synaptosomal newly synthesized NF proteins is drastically different from that of the NF proteins synthesized by nerve cell bodies. The latter results exclude the possibility that NF proteins synthesized by the synaptosomal fraction originate in fragments of nerve cell bodies possibly contaminating the synaptosomal fraction. They rather indicate that in squid brain, nerve terminals synthesize NF proteins. PMID- 8360681 TI - Chronic ethanol reduces immunologically detectable Gq alpha/11 alpha in NG108-15 cells. AB - Recent work has shown that chronic ethanol treatment inhibits receptor-stimulated phosphoinositide hydrolysis in NG108-15 cells and that ethanol exerts this effect primarily at the level of the guanine-nucleotide binding protein (G protein). Here we investigated the effects of ethanol exposure on the expression of Gq alpha/11 alpha, two highly homologous G protein alpha-subunits that have been implicated as regulators of phosphoinositidase C. Addition of ethanol (10-200 mM) to the culture medium for 48 h caused a concentration-dependent decrease in the immunologically detectable levels of Gq alpha/11 alpha. A small (approximately 15%) reduction in Gq alpha/11 alpha was observed after only 6 h of exposure to 200 mM ethanol, but membrane levels were reduced by 31% at 48 h. The ethanol induced loss of Gq alpha/11 alpha was apparently independent of factors present in the foetal calf serum component of the culture medium. These results suggests that the decrease in receptor-mediated phosphoinositide hydrolysis following chronic ethanol treatment of NG108-15 cells may be mediated in part by a reduction in the membrane levels of Gq alpha/11 alpha. PMID- 8360682 TI - Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. AB - A major pathological feature of Alzheimer's disease (AD) is the presence of a high density of amyloid plaques in the brain tissue of patients. The plaques are predominantly composed of human beta-amyloid peptide beta A4, a 40-mer whose neurotoxicity is related to its aggregation. Certain metals have been proposed as risk factors for AD, but the mechanism by which the metals may exert their effects is unclear. Radioiodinated human beta A4 has been used to assess the effects of various metals on the aggregation of the peptide in dilute solution (10(-10) M). In physiological buffers, 10(-3) M calcium, cobalt, copper, manganese, magnesium, sodium, or potassium had no effect on the rate of beta A4 aggregation. In sharp contrast, aluminum, iron, and zinc under the same conditions strongly promoted aggregation (rate enhancement of 100-1,000-fold). The aggregation of beta A4 induced by aluminum and iron is distinguishable from that induced by zinc in terms of rate, extent, pH and temperature dependence. These results suggest that high concentrations of certain metals may play a role in the pathogenesis of AD by promoting aggregation of beta A4. PMID- 8360683 TI - Tau in paired helical filaments is functionally distinct from fetal tau: assembly incompetence of paired helical filament-tau. AB - tau in paired helical filaments (PHF-tau) and fetal tau share several phosphorylated epitopes, as revealed by several phosphorylation-dependent PHF monoclonals. We have asked whether there is any difference between the two molecules in tubulin assembly-promoting activity and found that PHF-tau is almost assembly incompetent, whereas fetal tau is low in this activity but still assembly competent. This indicates that despite substantial similarities in immunoreactivities, PHF-tau and fetal tau are quite distinct from each other in function. PMID- 8360684 TI - Evolving concepts about the role of acidosis in ischemic neuropathology. AB - Cerebral ischemia is one of the most common neurological insults. Many pathological events are undoubtedly triggered by ischemia, but only recently has it become accepted that ischemic cell injury arises from a complex interaction between multiple biochemical cascades. Tissue acidosis is a well established feature of ischemic brain tissue, but its role in ischemic neuropathology is still not fully understood. Within the last few years, new evidence has challenged the historically negative view of acidosis and suggests that it may play more of a beneficial role than previously thought. This review reintroduces the concept of acidosis to ischemic brain injury and presents some new perspectives on its neuroprotective potential. PMID- 8360685 TI - Antibodies raised against synthetic peptides react with choline acetyltransferase in various immunoassays and in immunohistochemistry. AB - Antisera were raised in rabbits against five synthetic peptides. These peptides have been identified as potentially antigenic epitopes from the sequence of porcine choline acetyltransferase (ChAT) using primary and secondary structure analysis. All five antisera recognized immunoaffinity-purified antigen from porcine brain in an ELISA and on western blots. Four antisera recognized ChAT on dot blots, and another four antisera reacted with native and degraded enzyme in a sandwich ELISA using monoclonal antibodies as the capture antibody. One peptide antiserum was of similar avidity in this sandwich ELISA as a polyclonal antibody raised against immunoaffinity-purified ChAT. The same antiserum reacted with the enzyme from human placenta in an ELISA and on western and dot blots and recognized ChAT in rat, primate, and human neurons. Thus, a single peptide (amino acids 168-189) provides the means for easy, reliable, and reproducible generation of antibodies against ChAT suitable for replacing conventional polyclonal and monoclonal antibodies. PMID- 8360686 TI - Detection of intracellular free Na+ concentration of synaptosomes by a fluorescent indicator, Na(+)-binding benzofuran isophthalate: the effect of veratridine, ouabain, and alpha-latrotoxin. AB - A novel fluorescent Na+ indicator, Na(+)-binding benzofuran isophthalate (SBFI), was used to follow changes in the intracellular free Na+ concentration ([Na+]i) of synaptosomes. The dye, when loaded into synaptosomes in the form of its acetoxymethyl ester, was responsive to changes of [Na+]. Calibration was made using the 340/380 nm excitation ratio when the cytoplasmic Na+ concentration was equilibrated with different concentrations of extracellular Na+ in the presence of 2 microM gramicidin D. The basal value of [Na+]i in synaptosomes in the presence of 140 mM extracellular Na+ was found to be 10.9 +/- 1.8 mM. Veratridine, which opens potential-dependent Na+ channels, caused a sudden increase in [Na+]i in a concentration-dependent manner (1-20 microM), whereas the effect of ouabain (20 and 50 microM), the inhibitor of the plasma membrane Na+,K(+)-ATPase, was more gradual. The rise in the fluorescence intensity upon addition of veratridine was prevented completely by 2 microM tetrodotoxin. alpha Latrotoxin, the black widow spider toxin, caused an increase in the fluorescence intensity, which became evident 1 min after the addition of the toxin. The rate of increase was proportional to the concentration of the toxin (0.19-1.5 nM). This report confirms our earlier finding demonstrating a Na(+)-dependent component in the action of alpha-latrotoxin, and shows that changes in [Na+]i in synaptosomes can be followed by SBFI. PMID- 8360687 TI - Cytochalasin modulation of nicotinic cholinergic receptor expression and muscarinic receptor function in human TE671/RD cells: a possible functional role of the cytoskeleton. AB - Previous studies have shown that cells of the TE671/RD human clonal line express muscle-type nicotinic acetylcholine receptors (nAChR) and m3-type muscarinic acetylcholine receptors (mAChR) whose numbers and function are regulated by agonist treatment and second messenger modulation. Here we show that cytochalasin treatment, which causes disruption of actin networks, induces marked changes in the numbers and distribution of nAChR, but not mAChR. Moreover, whereas cytochalasin treatment fails to alter nAChR function significantly, it acutely potentiates mAChR-mediated phosphoinositide hydrolysis. Treatment of TE671/RD cells with different cytochalasin analogues (rank order efficacy at 5 micrograms/ml is H > J = B = C = D > A = E) produces a two- to fourfold increase in numbers of membrane-bound nAChR (Bmax in units of specific 125I-labeled alpha bungarotoxin binding per milligram of membrane protein). nAChR up-regulation is evident after 1-2 days of cytochalasin B exposure, is maximal after 3-6 days of drug treatment, and is dominated by an approximately 10-fold increase (per cell) in an intracellular nAChR pool. Cytochalasin-induced nAChR up-regulation is similar in magnitude to, but not additive with, up-regulation of nAChR following chronic exposure to nicotine or phorbol ester. Northern blot analysis shows a four- to five-fold coordinate increase in levels of mRNA that encode nAChR alpha, beta, gamma, or delta subunits in cytochalasin-treated cells, suggesting that nAChR up-regulation has a possible transcriptional basis. Studies done using a 86Rb+ efflux assay indicate that cytochalasin treatment has no significant effect on nAChR function. By contrast, cytochalasin treatment has no effect on the numbers of mAChR as assessed by binding studies with the radioantagonist 3H labeled quinuclidinyl benzilate, but it induces marked enhancement of carbachol stimulated, but not basal, phosphoinositide hydrolysis. These studies suggest that presumed modulation by cytochalasin treatment of cytoskeletal microfilament integrity can differentially influence expression and function of mAChR (a prototype of the metabotropic receptor superfamily) and nAChR (a prototype of the ligand-gated ion-channel superfamily). The results also suggest possible new roles for the cytoskeleton in regulation of membrane receptor expression, function, and cross talk. PMID- 8360688 TI - Heterogeneity of the high molecular weight tau proteins in N115 neuroblastoma cells. AB - The sequence of a high molecular weight (HMW) tau cDNA cloned from a neuroblastoma N115 library contains, in addition to the C- and N-terminal and middle regions present in the low molecular weight mouse brain tau proteins, a 711-bp nonhomologous domain (exon 4a) and a region of 198 bp corresponding to exon 6 of the tau gene. Protein immunoblot analysis, performed with antibodies specific either for a sequence present in the N-terminal region of all the tau variants or for exon 4a revealed several bands suggesting that more than one tau form is expressed in this cell line. Northern blot experiments performed with a number of cDNA probes spanning domains common and uncommon to low molecular weight and HMW tau allowed the identification of four tau transcripts differing in the size of their coding and noncoding regions. All these transcripts contain the sequence encoded by exon 6, but two of them lack exon 4a. As shown by RNase protection assays, the N-terminal region of these transcripts is also variable and contains either exon 1, or exons 1 and 2, or exons 1-3. Yet all these HMW tau forms contain four homologous repeats in their C-terminal domain both in the differentiated and nondifferentiated cells, i.e., have adult characteristics. In conclusion, the data reported in this article demonstrate that several HMW tau variants are expressed in neuroblastoma N115 cells and that the transition between immature to mature tau forms occurring during brain development is not required for neurite outgrowth during morphological differentiation of this cell line. PMID- 8360689 TI - Effects of chronic basic fibroblast growth factor administration to rats with partial fimbrial transections on presynaptic cholinergic parameters and muscarinic receptors in the hippocampus: comparison with nerve growth factor. AB - The present study compares the effects of chronic administration of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on various hippocampal cholinergic parameters in rats with partial unilateral fimbrial transections. Lesions resulted in marked reductions of several presynaptic cholinergic parameters: choline acetyltransferase (ChAT) activity (by 50%), [3H] acetylcholine ([3H]ACh) synthesis (by 59%), basal and veratridine (1 microM) evoked [3H]ACh release (by 44 and 57%, respectively), and [3H]vesamicol binding site densities (by 35%). In addition, [3H]AF-DX 116/muscarinic M2 binding site densities were also modestly decreased (by 23%). In contrast, [3H]pirenzepine/muscarinic M1 and [3H]AF-DX 384/muscarinic M2/M4 binding site densities were not altered by the lesions, nor were they affected by any of the treatments. Intracerebroventricular administration of bFGF (10 ng, every other day, for 21 days) partially prevented the lesion-induced deficit in hippocampal ChAT activity, an effect that was not markedly different from that measured in the NGF-treated (1 microgram, intracerebroventricularly, every other day, for 21 days) rats. In rats treated with a combination of bFGF and NGF, ChAT activity was not different from that in rats treated with the individual factors alone. In contrast, the lesion-induced deficits in the other cholinergic parameters were not attenuated by bFGF treatment, although they were at least partially prevented by NGF administration. To determine whether higher concentrations of bFGF are necessary to affect cholinergic parameters other than hippocampal ChAT activity, rats were treated with 1 microgram (every other day, 21 days) of the growth factor. In this group of rats, detrimental effects of bFGF, manifested by an increased death rate (46%), and marked reductions in body weight of the survivors, were observed. In addition, this concentration of bFGF appeared to exacerbate the lesion-induced reduction in [3H]ACh synthesis by hippocampal slices; [3H]ACh synthesis in lesioned hippocampi represented 36 and 52% of that in contralateral unlesioned hippocampi for the bFGF-treated and control groups, respectively. In conclusion, although bFGF administration attenuates the deficit in hippocampal ChAT activity induced by partial fimbrial transections, this does not appear to translate into enhanced functional capacity of the cholinergic terminals. This is clearly in contrast to NGF, which enhances not only hippocampal ChAT activity, but also other parameters indicative of increased function in the cholinergic terminals. PMID- 8360690 TI - Nonenzymatic conversion of 3,4-dihydroxyphenylalanine to 2,4,5 trihydroxyphenylalanine and 2,4,5-trihydroxyphenylalanine quinone in physiological solutions. AB - 2,4,5-Trihydroxyphenylalanine (TOPA) oxidizes in solution to form a quinone derivative that is a non-N-methyl-D-aspartate agonist and neurotoxin. Although pathways have been postulated for the formation of both TOPA and TOPA quinone from closely related catecholamines, the generation of these compounds has not been conclusively demonstrated by analytical techniques. Reverse-phase HPLC with a dual electrode coulometric detector was used to analyze TOPA containing solutions in an effort to rigorously characterize the behavior of this substance under physiological conditions. Electrode potential, buffer system, and methanol concentration were varied to obtain optimal conditions to selectively detect and quantify TOPA and TOPA quinone from closely related catecholamines. TOPA was shown to rapidly autoxidize to TOPA quinone by a process dependent on pH. TOPA was the dominant species at acidic pHs (below 5-6), whereas TOPA quinone was dominant at physiological pHs. This conversion was reversible upon acidification. In addition, we found that 3,4-dihydroxyphenylalanine can autoxidize to form both TOPA and TOPA quinone under physiological conditions. This partial conversion (0.5%) is time dependent and can be substantially decreased (0.2%) in acidic conditions (pH < or = 3). These results suggest that some of the excitatory and excitotoxic properties that some investigators have attributed to DOPA may actually be due to its conversion to TOPA and TOPA quinone. PMID- 8360691 TI - The presence of (+)-S-adenosyl-L-methionine in the rat brain and its lack of effect on phenylethanolamine N-methyltransferase activity. AB - (+)-S-Adenosyl-L-methionine [(+)-SAM] was isolated from rat brain and was quantified by HPLC followed by UV spectrophotometric measurements and by 1H-NMR. Its estimated ratio in brain is 3% of total SAM. Because of its commercial unavailability, (+)-SAM was also prepared from chemically synthesized SAM by separation of the two diastereoisomers on a preparative reverse-phase Nucleosil C8 column. The (+) diastereoisomer thus obtained was then assayed in vitro both as an inhibitor and a substrate of phenylethanolamine N-methyltransferase. Enzymatic activity was measured by HPLC analysis. It was shown that (+)-SAM has no effect on phenylethanolamine N-methyltransferase activity; therefore, it is unlikely that (+)-SAM plays any possible role in regulation of adrenaline synthesis in the brain. PMID- 8360692 TI - Microdialysis of melatonin in the rat pineal gland: methodology and pharmacological applications. AB - The present study describes the development of a new technique to measure melatonin contents in the pineal gland of freely moving rats, by means of on-line microdialysis. The transcerebral cannula was modified, and a sensitive assay of melatonin, using HPLC with fluorimetric detection, was set up. With this system it is possible to monitor the melatonin levels on-line in the pineal gland during day- and nighttime. The nightly increase in melatonin release was recorded. Tetrodotoxin had an inhibitory effect on nighttime levels, whereas even high concentrations did not alter the daytime level. From this we conclude that neuronal activity is necessary to synthesize melatonin and that during daytime no net neuronal activity is present. Melatonin levels could be greatly enhanced by systemic administration of the beta-agonist isoprenaline (ISO). Also, local infusion of ISO or 8-bromoadenosine 3',5'-cyclic monophosphate, an analogue of the second messenger cyclic AMP, resulted in increased melatonin levels, demonstrating the presence of beta-adrenergic receptors, coupled to a cyclic AMP based second messenger system, on the pineal gland. Injection of phenylephrine had no effect on daytime levels. Only when administered during ISO-induced stimulation of melatonin release did it enhance this stimulated release. This proved the regulatory role of alpha 1-receptors on pinealocytes. The method presented is of special interest for investigating the innervation of the pineal gland and the biochemical processes that regulate the biosynthesis of melatonin. Also, for studies on the diurnal rhythms of melatonin release and factors that influence these rhythms in freely moving animals, this model will be of great value. PMID- 8360693 TI - ATP-sensitive potassium channels and local energy demands in the rat hippocampus: an in vivo study. AB - Microdialysis coupled with an enzyme-based flow injection analysis was used to monitor brain extracellular lactate and glucose in the freely moving rat. Glucose levels reflect the balance between supply from the blood and local utilisation, and lactate efflux indicates the degree of local nonoxidative glucose metabolism. Local application of tolbutamide, a blocker of the ATP-sensitive potassium channel, decreased extracellular glucose and lactate levels in the hippocampus but not in the striatum. The increase in glucose and lactate levels following mild behavioural stimulation was also reduced by tolbutamide in the hippocampus. Similar effects on both basal and stimulated lactate levels were obtained with local application of 10 mM glucose. These results indicate that ATP-sensitive potassium channels are active under physiological conditions in the hippocampus and that the effects of tolbutamide can be mimicked by physiological glucose levels. PMID- 8360694 TI - Age-related changes in the ceramide composition of the major gangliosides present in rat brain subcellular fractions enriched in plasma membranes of neuronal and myelin origin. AB - Age-related changes of the ceramide composition of gangliosides were studied in the synaptosomal and myelin fractions from rat brain, carrying plasma membranes of neuronal and glial origin, respectively. The five major gangliosides (GM1, GD1a, GD1b, GT1b, and GQ1b) present in these fractions were separated and quantitated by normal-phase HPLC. Each ganglioside was then fractionated by reverse-phase HPLC into the molecular species carrying a single long-chain base (LCB). The largely preponderant LCBs in the synaptosomal and myelin fractions were the C18:1 and C20:1. The content of C20:1 LCB, generally low at 1 month, increased with age in all analyzed gangliosides and in all subcellular fractions and was greater in the "b series" than in the "a series" gangliosides. Remarkably, GM1 was the only ganglioside where the proportion of LCB 20:1 was higher in the synaptosomal fraction than in the myelin fraction. The fatty acid composition of the C18:1 or C20:1 LCB species of the different gangliosides in the synaptosomal and myelin fractions did not undergo appreciable changes with age. Stearic acid was largely predominant in all the gangliosides of the synaptosomal fraction, more in the C18:1 than in the C20:1 LCB species (80-90% vs. 60-70%). The gangliosides of the myelin fraction were characterized by a lower content of 18:0 and a much higher content of 16:0 and 18:1 fatty acids than those of the synaptosomal fraction. Thus, the ceramide composition is different in the gangliosides of neuronal and myelin origin and appears to be subjected to an age-related control. PMID- 8360695 TI - A tau fragment containing a repetitive sequence induces bundling of actin filaments. AB - Much indirect evidence suggests that the interconnections of actin microfilaments with the microtubule system are mediated by microtubule-associated proteins (MAPs). In this study we provide new data to support the interaction of a specific tubulin-binding domain on tau with actin in vitro. In actin polymerization assays, the synthetic peptide VRSKIGSTENLKHQPGGG, corresponding to the first repetitive sequence of tau protein, increased turbidity at 320 nm in a dose-dependent fashion. A salient feature of the tau peptide-induced assembly process is the formation of a large amount of actin filament bundles, as revealed by electron microscopic analysis. An increase in the tau peptide concentration resulted in a proportional increase in the bundling of actin filaments. It is interesting that a gradual decrease of pH within the range 7.6-4.7 resulted in a higher effect of tau peptide in promoting bundles of actin filaments. A similar pH-dependent effect was observed for tau protein-induced bundling. An analysis of the mechanisms that operate in the peptide induction of actin filament bundles suggests the involvement of electrostatic forces, because the neutralization of epsilon-aminolysyl residues by selective carbamoylation resulted in a complete loss of the peptide induction of actin bundles. The data suggest that a tau repetitive sequence (also found in MAP-2 and MAP-4) containing a common tubulin binding motif may constitute a functional domain on tau for the dynamics of the interconnections between actin filaments and microtubules. PMID- 8360696 TI - The balance between tau protein's microtubule growth and nucleation activities: implications for the formation of axonal microtubules. AB - The microtubule-associated protein tau is found primarily in neuronal tissues and is highly enriched in the axon. It promotes microtubule assembly in vitro and stabilizes microtubules in cells. To study how tau protein might be involved in the unique features of axonal microtubules, we have analyzed the effect of E. coli-synthesized tau protein using an in vitro centrosome-mediated microtubule regrowth assay over a wide range of tau/tubulin ratios. We report that microtubule assembly promoted by tau protein exhibits characteristic changes dependent on the tau/tubulin ratio. Above a threshold level, nucleation of new microtubules is favored over growth of existing ones. tau isoform variation does not change this phase transition in microtubule assembly. We discuss how tau might participate in the elaboration of axonal morphology based on our results and present evidence that the phase transition from microtubule growth to nucleation is critical for axonal development. PMID- 8360697 TI - The neuropathology of temporal lobe epilepsy. AB - Complex partial epilepsy arising in the temporal lobe has been associated with several types of pathologic lesions including Ammon's horn sclerosis, malformations, neoplasms, and inflammatory scars from infarcts or infection. These lesions are usually situated at various sites in the medial temporal lobe, so that one of the enigmas of attempting to understand the pathogenesis of TLE pertains to the clinical manifestation of a single epileptic disorder which is associated with dissimilar lesions at dissimilar sites. Recent demonstrations of an alteration in temporal lobe anatomy, i.e. malformations of the normal circuitry of the temporal lobe and foci of microdysgenesis, have given rise to the hypothesis that insults which occur during a critical period of brain development could alter the connections within the hippocampus and predispose it to increased excitability and seizurogenesis. Such a hypothesis forces us to reconsider TLE in reference to risk factors which may act as "teratogens" and produce these malformations. These malformations may range from a subtle alteration in the neurotransmitters of the dentate gyrus to large areas of cortical dysplasia or the hamartomatous neoplasms seen in TLE. A reevaluation of the neuroanatomical disruptions created by the various lesions may allow us to define a minimal optimal surgical resection for each lesion; or, the definitions of neurotransmitter deficits may lead to alternative pharmacologic therapies. As neuropathologists we have the exciting opportunity to participate in the definition of the neuropathology of temporal lobe epilepsy. PMID- 8360698 TI - Renaut bodies contain elastic fiber components. AB - Renaut bodies (RB) are fusiform endoneurial structures preferentially found at sites of nerve entrapment, often occupying more than 30% of the cross-sectional area of a nerve fascicle. Their composition and significance, however, are still incompletely understood. In this study, further evidence for the link between the appearance of RB and nerve entrapment is presented. Reanaut bodies were already found at the age of 1 year in the median nerve at the level of the wrist, i.e. in the carpal tunnel, a possible site of entrapment. Here, their number increased with age. Renaut bodies were absent, however, in fetal nerves at this site. Many of the cells in RB resembled perineurial cells or pericytes. They were stained with antibodies against vimentin and epithelial membrane antigen and were partially covered by a basal lamina reactive with antibodies against collagen IV, laminin, and s-laminin. Focally accumulated filaments and bundles of 30-40 nm collagen fibrils were major extracellular components of RB. The diameter of the filaments (8-12 nm) corresponded to the size of the microfibril, i.e. the oxytalan component of elastic fibers. Renaut bodies were intensely stained with antibodies against these microfibrils and several types of collagen glycoproteins. On the basis of these results, we conclude that RB are composed of cells that show perineurial differentiation. These cells produce an extracellular matrix highly enriched in elastic fiber components. PMID- 8360699 TI - Spatial distribution of nerve injury after occlusion of individual major vessels in rat sciatic nerves. AB - In an attempt to better understand the spatial distribution of ischemic injury secondary to occlusion of major arteries, we measured nerve blood flow (NBF) and studied morphologic changes at various levels distal to the ligature site. Arterial ligation of the femoral, internal iliac, or superior gluteal artery was preceded and followed by measurement of NBF using laser Doppler flowmetry which helped identify "watershed areas" and guided the sampling process as nerves were examined pathologically and areas of injury were identified. Femoral artery ligation produced the most severe ischemia, focally reducing NBF by 80% in the tibial nerve at a level just below the knee. Within these ischemic nerve segments there were degenerative changes of nerve fibers seen mainly in the subperineurial region. Ligation of the internal iliac artery caused an approximately 60% reduction in NBF at the upper and mid-thigh levels of the sciatic nerve which resulted only in endoneurial edema in tissue taken at this level. Following superior gluteal artery ligation. NBF was reduced by only 20% at the pelvic level of the sciatic nerve and there was neither endoneurial edema nor fiber abnormalities. This study demonstrates the watershed pattern of ischemic injury associated with single vessel ligation by correlating neuropathologic change with quantitative measures of local nerve blood flow. The data further support the concept that mild levels of ischemia cause endoneurial edema, while moderate levels of ischemia produce demyelination and severe ischemia produces Wallerian degeneration. PMID- 8360701 TI - Histologic assessment of the age of recent brain infarcts in man. AB - In order to design a dating system based on the microscopic picture of brain infarcts of recent onset, we performed the histological examination of 31 infarcts covering the first 4 weeks of evolution in 30 autopsy cases. The date of the cerebral vascular accident was clinically established in every case. There were 13 men and 17 women with a mean age of 65 years. Hemorrhagic infarcts were found in 15 cases and anemic infarcts in 16 cases. Based on the histological features four periods were identified: the first period, from day 1 through day 4, was characterized by the predominance of eosinophilic neurons and necrotic oligodendrocytes; the second period, from day 5 through day 7, differed from the first by the appearance of macrophages and of newly formed blood vessels; the third period, from day 8 through day 14, showed neuronal ghosts, macrophages, astrocytic proliferation, gemistocytes, and absence of neutrophils; and in the fourth period, from day 15 through day 27, there were no eosinophilic neurons, and neither necrotic oligodendrocytes nor myelin in the central portion of the infarct were identified. By assessing the histological features and accurately correlating the findings with the corresponding clinical data, we have been able to describe four distinct microscopic patterns of the first month of evolution of brain infarcts. The present findings may be considered useful morphological clues to better characterize the early evolutional phase of brain infarcts in humans. PMID- 8360700 TI - Brain structures selectively targeted by canine distemper virus in a mouse model infection. AB - Paramyxoviruses such as measles virus or canine distemper virus are etiological agents for acute and chronic encephalitis (measles inclusion body encephalitis, subacute sclerosing panencephalitis and chronic distemper encephalitis or old dog encephalitis). The mechanisms by which viral injury leads to neurological diseases have not yet been fully elucidated. We have developed an experimental model in mice in order to analyze the spatial and temporal distribution of canine distemper virus in the central nervous system. Cerebral target structures for viral replication were examined for the presence of viral material (proteins and mRNA) during the two stages of the biphasic disease. During the acute stage of infection all target areas could be identified by day 6 with a similar anatomical distribution in all the animals examined, which were either intracranially or intracerebroventricularly infected. Viral mRNA and proteins were selectively localized in certain brain structures such as the thalamus, hypothalamus, substantia nigra (pars compacta), locus ceruleus and raphe nuclei (dorsalis and centralis), and limbic system (hippocampus, septum, entorhinal and cingulate cortex, amygdala). The virus was apparently unable to replicate in cerebellum, striatum, a large part of cortex, or endothelial cells. During the subacute disease, viral material was no longer detectable except in a few structures such as hypothalamus up to 4-6 weeks after inoculation. After this time, all target structures were devoid of any labeling in spite of the occurrence of pathology (obesity, paralysis) during this viral quiescent phase. These results suggest that after the initial viral exposure, expression of viral genes in defined structures might disrupt central homeostasis and finally may lead to neurological or neuroendocrine diseases, even in the absence of the hallmarks of the virus. PMID- 8360702 TI - Effects of psychosine (galactosylsphingosine) on the survival and the fine structure of cultured Schwann cells. AB - The cytotoxicity of psychosine (galactosylsphingosine) for cultured rat Schwann cells was studied by maintaining them in medium containing 1, 10, 50, 75 and 100 microM psychosine for 24, 48 and 72 hours (h). When incubated in 50-100 microM concentrations of psychosine for 24 h, 52-99% of cultured Schwann cells did not survive. Lower concentrations (1-10 microM) did not significantly reduce Schwann cell numbers for the first 24 h. However, only 43-69% of cultured Schwann cells survived in these low concentrations for 48 h, and substantially fewer remained after 72 h of incubation. During incubations in psychosine, bipolar processes of Schwann cells retracted; the resulting oval and rounded Schwann cells still were S-100 positive. When these Schwann cells were transferred into normal medium, their processes elongated quickly. When examined with the electron microscope, the cytoplasm of Schwann cells incubated in psychosine contained numerous membranous inclusions and fewer mitochondria, some of which were swollen. There also were fewer profiles of granular endoplasmic reticulum and some had widely dilated cisternae. These results suggest that 1) exogenous psychosine in concentrations of 1 microM and greater is cytotoxic for cultured rat Schwann cells; 2) psychosine has reversible toxic effects and its turnover is rapid; and 3) psychosine produces membranous inclusions and abnormalities in the mitochondria and granular endoplasmic reticulum of cultured Schwann cells. Our findings support the hypothesis that the accumulation of psychosine in human and murine globoid cell leukodystrophy is toxic for Schwann cells, produces changes in their capacity to maintain myelin, and leads to Schwann cell dysfunction. PMID- 8360703 TI - Surgical pathology of temporal lobe epilepsy. Experience with 216 cases. AB - The surgical treatment of chronic epilepsies is increasing rapidly. Here we report the histopathologic findings in 216 consecutive surgical specimens of patients with chronic pharmacoresistant temporal lobe epilepsy. In 75 cases (34.7%) there were tumors, all but two of which were of low histopathological grade (WHO grade I or II). The most common tumors were gangliogliomas (34 cases), pilocytic astrocytomas (17 cases), oligodendrogliomas (9 cases), fibrillary astrocytomas (6 cases), and dysembryoplastic neuroepithelial tumors (6 cases). There were 51 cases with non-neoplastic focal lesions and an additional 13 cases with tumors and non-neoplastic focal lesions within the same specimen. The most frequent non-neoplastic focal lesions were microscopic glioneuronal hamartias (32 cases), glioneuronal hamartomas (7 cases), and vascular malformations (13 cases). The hippocampal formation was structurally well preserved in 71 specimens. In 51 of these (71.8%) there was Ammon's horn sclerosis. Presurgical placement of depth electrodes was invariably associated with circumscribed defects of the brain parenchyma. The implantation of subdural electrodes was sometimes followed by chronic inflammatory changes of the leptomeninges. Our findings indicate that in the majority of patients with medically intractable temporal lobe epilepsy there are significant histopathologic findings, many of which are only rarely encountered otherwise. PMID- 8360704 TI - Differential expression of retinal proteins in a pineal parenchymal tumor. AB - The pineal gland and retina share histogenetic features that reflect a similar neurosensory/photosensory ontogeny. Pineal parenchymal tumors demonstrate a highly variable and incomplete photosensory differentiation evidenced by specific cytoarchitectural features and the expression of photosensory retinal S-Antigen (S-Ag). Despite these neuro-ontogenetic parallels, pineal parenchymal tumors have not been well studied for the neuroretinal phenotypes that accompany normal neuroretinal development. The investigation of photoreceptor gene expression may provide an important insight into the histogenesis of pineal parenchymal neoplasms. In this study, a pineal parenchymal tumor of the "mixed pineoblastoma/pineocytoma" type was examined for the expression of several photoreceptor, glial and neuronal proteins including: interphotoreceptor retinoid binding protein (IRBP), rod opsin, cone opsin, S-Ag and cellular retinaldehyde binding protein (CRA1BP). The detection of IRBP and its mRNA, the earliest photoreceptor-associated protein expressed during retinal development, corroborated the rudimentary photosensory differentiation of this tumor which had limited cytoarchitectural evidence for pineal differentiation. The analysis of IRBP expression may facilitate the diagnostic recognition of primitive pineal neoplasms and further define the neuroretinal differentiation which occurs in pineal parenchymal tumors. PMID- 8360705 TI - Ependymal abnormalities in lissencephaly/pachygyria. AB - The ependyma was examined in eight children with neuroblast migratory disorders of diverse origin: three cases of lissencephaly type 1 with severe to mild degrees of agyria/pachygyria, four cases of lissencephaly type 2 in Fukuyama muscular dystrophy and the Walker-Warburg syndrome, and one case of hemimegalencephalic pachygyria. Morphological and immunohistochemical abnormalities of the ependyma were strikingly similar in all. Discontinuities were disproportionate to the degree of ventriculomegaly. In some regions, the ependyma remained a pseudostratified columnar epithelium, though basal processes were absent. The poles of the horns of the lateral ventricles were replaced by extensive heterotopic ependymal rosettes. Rosettes and rows of ependyma also were in other subventricular sites. Subependymal nodules of large astrocytes and their processes bulged into the ventricular lumen after infancy. Ependymal cells did not express glial fibrillary acidic protein, but showed persistent expression of S-100 protein, cytokeratin CK-904 and sometimes vimentin long after these proteins normally disappear. An abnormal ependyma in lissencephaly/pachygyria may contribute to disturbances in neuronogenesis, guidance of axonal projections and neuroblast migrations; it may be a primary factor in pathogenesis. PMID- 8360706 TI - Experimental lovastatin myopathy. AB - Lovastatin (LS) is a potent HMG-CoA inhibitor used in the treatment of hypercholesterolemia. In humans it can cause a severe, necrotizing myopathy with myoglobinuria and renal failure. To investigate the pathogenesis of LS-induced myopathy we studied the effects of LS on rat skeletal muscle. Lewis rats were gavage-fed 1 mg/g body weight/day of LS. Control rats received carboxymethylcellulose-based suspension by gavage. Gastrocnemius and soleus, fast and slow twitch muscles respectively, were studied by light and electron microscopy. By day 10 LS-treated rats became severely weak. Gastrocnemius was severely affected with degeneration of membranous organelles and microvacuole formation, but soleus was spared. Eventually, 20-50% of the gastrocnemius but none of the soleus fibers became necrotic. Non-necrotic fibers showed no increases of acid phosphatase, indicating that autophagy was not excited. We conclude that LS causes muscle injury by inducing degeneration of membranous organelles, and fast twitch muscle fibers are selectively vulnerable to LS myopathy. PMID- 8360707 TI - Responses of human glioblastoma cells to human natural tumor necrosis factor alpha: susceptibility, mechanism of resistance and cytokine production studies. AB - Responses and susceptibility of 14 human glioblastoma cell lines to human natural tumor necrosis factor-alpha (TNF) were studied in vitro. Susceptibility of glioblastoma cells to TNF varied in experimental conditions applied. Most of glioblastoma cell lines were resistant to cytotoxic activity of TNF in a MTT assay at concentrations below 16 U/ml for 72 h exposure. However, TNF at higher dose, in prolonged exposure and against low density of target cells was antiproliferative for certain glioblastoma cultures. TNF exposure at 10 U/ml for 48 h suppressed DNA synthesis in 9 of 14 glioblastoma cultures, but increased in 3 cultures. In addition, colony forming assay showed anti-clonogenic activity of TNF in 5 of 6 glioblastoma cell lines tested. In spite of their low susceptibility to TNF, glioblastoma cells well responded to TNF stimulation at low dose (10 U/ml) for a short period in the absence of cell damage. Productions of Interleukin-6 (IL-6), IL-8-like activity, granulocyte-macrophage colony stimulating factor (GM-CSF), prostaglandin E2 (PGE2) and manganous superoxide dismutase (Mn-SOD) were enhanced or induced by the low-dose TNF stimulation. Mn SOD, a protein protective against oxidative cell damage, was well induced in time and dose-dependent manner, however did not correlate with TNF resistance. Whereas the levels of PGE2 in TNF-susceptible cell lines, H-4 and SF-188, were higher than those of other lines. In conclusion, most of glioblastoma cells are resistant to TNF cytotoxic effects, but highly responsive to TNF stimulation. Its effect on glioblastoma cells appears to modulate cell differentiation rather than to kill the cells. PMID- 8360708 TI - (14C-methyl)-L-methionine uptake in rat brain tumors before and after treatment with the protein synthesis inhibitor cycloheximide. AB - Autoradiographic study of (14C-methyl)-L-methionine with brain tumor bearing rats aimed at an elucidation of the mechanism of tracer accumulation in the protein synthesis of tumor. Twice as much tracer accumulated in the tumors compared as in the contralateral gray matter (nontumor region) at 90 min post intravenous injection. The protein-bound fraction of the tumors, expressed as acid-insoluble fraction (AIF), was 1.7 +/- 0.6 (mean +/- standard deviation, n = 6), significantly higher than that (0.8 +/- 0.2) of the nontumor region (p < 0.05 by the Mann-Whitney test). The tumor AIF comprised 82.3 +/- 9.2% of the total amount of the tracers accumulated in the tumors. The protein synthesis inhibitor cycloheximide reduced the tracer uptake and the AIF of the tumors to an almost same level as the nontumor region. These findings indicate that metabolic acceleration of protein synthesis may be a main reason for the high accumulation of (14C-methyl)-L-methionine in tumor. PMID- 8360709 TI - Treatment of spinal epidural neuroblastoma xenografts in rats using anti-GD2 monoclonal antibody 3F8. AB - Epidural neuroblastoma xenografts in nude rats causing paraparesis were treated with intravenous injection of an anti-GD2 monoclonal antibody 3F8. Metastatic or primary epidural tumors in humans cause rapid neurologic compromise. Treatment is often unsatisfactory. An animal model was established to study antibody targeted therapy of epidural tumor. Human neuroblastoma was xenotransplanted into the thoracic epidural space of nude rats. When paraparesis developed, animals were treated intravenously with an anti-GD2 monoclonal antibody, 3F8, either alone or radiolabeled with 131Iodine. Improvement in neurologic function occurred in 2 of 20 (10%) animals receiving no treatment or control antibody, 14 of 17 (82%) animals receiving 3F8 alone and all 9 animals receiving 131I-3F8 (p < 0.0001 for 3F8 or 131I-3F8 vs. control). Six animals treated with 3F8 alone recovered normal neurologic function and remained well until sacrifice 10 days later. Four animals treated with 3F8 alone had no tumor evident on pathologic examination. The percent injected dose of 131I-3F8/g tumor in 5 samples ranged from 0.73% to 3.8%. These observations demonstrate that neoplastic epidural compression of the spinal cord in the rat can be treated successfully with intravenous unmodified monoclonal antibody and that signs of neurologic dysfunction can be reversed. The potential of this approach in treating patients with epidural tumors and other neoplasms, especially those that are not sensitive to chemotherapy or radiotherapy, deserves to be explored. PMID- 8360710 TI - Intracranial myxopapillary ependymoma: case report. AB - The authors report an unusual case of a myxopapillary ependymoma arising from the lateral ventricle. The patient, a 37-year-old woman, developed recurrent symptoms including scotomata, disorientation, and headache during two successive pregnancies before the definitive diagnosis. The causes of this ependymoma variant and its relationship to pregnancy are discussed. PMID- 8360711 TI - Comparison between BCNU and procarbazine chemotherapy for treatment of gliomas. AB - We compared sequential single-agent BCNU and procarbazine (PCB) chemotherapy in 31 patients with gliomas [grade IV (10), grade III (15), grade II (6)]. Patients had failed surgical biopsy +/- resection and radiation therapy. All patients were treated initially with BCNU 150-300 mg/m2 by intra-arterial or intravenous route every 6 weeks. After CT evidence of tumor progression, all patients received PCB 150 mg/m2/day for 28 days every 8 weeks. Patient responses to BCNU were CR (0), PR (7), SD (12), progression (12), and to PCB CR (2), PR (9), SD (6), and progression (14). Kaplan-Meier estimates of median time to failure for all patients were shorter for BCNU, 5.0 months (range 1.5-20), than for PCB, 6.0 months (range 2-50+). There was a statistically significant difference (Mantel Cox test, p = 0.02) in the distribution of time to disease progression between the two drugs, especially for grade III tumors (p = 0.02). The cumulative proportion of patients without disease progression at 6 months was 26% while on BCNU, compared to 48% while on PCB; at 12 months the cumulative proportions were 3% for BCNU compared to 35% for PCB. Although there was no formal washout period between administration of the two drugs, no carryover effect was evident. These data provide further evidence that PCB has significant activity against malignant glioma and may, in fact, be more effective than BCNU. PMID- 8360712 TI - Delayed neurotoxicity of intraventricular interleukin-2: a case report. AB - A case is reported of a 40 year old woman treated with intraventricular IL-2 for leptomeningeal disease who developed progressive cognitive dysfunction. This deterioration started 3 months post-treatment and worsened over the ensuing 4 years. MRI revealed white matter abnormalities that were not present on the pretreatment scan. Although free of disease, the patient has a subcortical dementia and is unable to work. The potential for progressive brain injury and subsequent disability related to intraventricular IL-2 therapy is discussed. PMID- 8360713 TI - Methotrexate induced brain necrosis and severe leukoencephalopathy due to disconnection of an Ommaya device. AB - A 63-year old woman with breast carcinoma developed leucoencephalopathy and local brain necrosis after intraparenchymal infusion of methotrexate. This iatrogenic condition was caused by drain disconnection of the Ommaya device (bore hole type). The diagnosis of this rare complication of an Ommaya device was based on multiplanar MR-imaging. The case is discussed with regard to the complications of intraventricular chemotherapy by means of an Ommaya reservoir. PMID- 8360714 TI - Primary diffuse leptomeningeal gliomatosis (PDLG): a neoplastic cause of chronic meningitis. AB - Cancerous 'chronic meningitis' may be related to subarachnoid space involvement by solid tumors, hematologic malignancies or rarely intraparenchymatous gliomas. Primary leptomeningeal gliomatosis is a rare condition that is attributed to malignant transformation of heterotopic neuroglial tissue. We discuss the clinical and biological features of a patient who died with the diffuse form of primary leptomeningeal gliomatosis (PDLG). A literature search shows that a one to two months long non-specific prodromal phase followed by a fluctuating neurologic downhill course is suggestive of this disease. Cerebro-spinal fluid (CSF) cytology has been diagnostic in only 1 of 8 reported cases. Recent technical progress, including the use of GFAP (glial fibrillary acidic protein) directed antibody, may enhance the sensitivity of CSF cytologies. Diagnosis may require repeated cerebral biopsies, because the hemispheric lesions are often separated by normal tissue. PDLG must be added to the large differential diagnosis of 'chronic meningitis'. PMID- 8360715 TI - Motor cortical activity during voluntary gait modifications in the cat. I. Cells related to the forelimbs. AB - 1. The discharge patterns of 91 identified pyramidal tract neurons (PTNs), located within the forelimb region of area 4 of the cat motor cortex, were recorded during the voluntary modifications of gait needed to step over obstacles attached to a moving treadmill belt. Recordings were made simultaneously from flexor and extensor muscles acting around the shoulder, elbow, wrist, and digits of the forelimb contralateral to the recording site. 2. Analysis of the changes in electromyographic (EMG) activity during the gait modification showed increases in the activity of most flexor muscles of the shoulder and elbow, as well as in the wrist and digit dorsiflexors, when the contralateral forelimb was the first to pass over the obstacle. This period of augmented activity could be subdivided into two parts: one associated with the initial flexion of the limb that was needed to bring it above and over the obstacle (phase I), and the second associated with increased wrist dorsiflexor muscle activity before foot contact (phase II). 3. The discharge frequency of a total of 57/91 (63%) of the recorded PTNs was significantly increased during the gait modification when the limb contralateral to the recording site was the first to step over the obstacle; six of these neurons also showed a significant decrease in their discharge in a different part of the step cycle. In a further 21/91 (23%) neurons, discharge frequency was only decreased, whereas the remaining 13/91 (14%) PTNs showed similar patterns of activity both during control walking and during the gait modifications. 4. Most of those neurons (47/57) in which significant increases in firing frequency were observed, discharged maximally during the period of increased activity of the physiological flexor muscles. Twenty-three of these cells (23/47) discharged maximally in phase I, and 12 (12/47) in phase II. A third population of PTNS (12/47) started to increase their discharge in the stance phase of the step cycle immediately preceding the modified cycle. Seven (7/57) PTNs increased their discharge during the stance phase of the modified cycle, and the remaining three could not be classified as being preferentially related to any one part of the step cycle. 5. The frequency modulation of 41/57 PTNs was less when the leg contralateral to the recording site was the second to encounter the obstacle. In many neurons there was also an appreciable change in the time in the step cycle that peak discharge occurred. These changes in amplitude and timing paralleled the changes observed in the temporal relationships of the muscles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360716 TI - Thermal and pain sensations evoked by microstimulation in the area of human ventrocaudal nucleus. AB - 1. We have studied the sensations evoked by threshold microstimulation (TMS) in the area of the human principal sensory nucleus of the thalamus [ventralis caudalis (Vc)] in patients (n = 11) undergoing stereotactic surgery for the treatment of movement disorders and pain. Preoperatively, patients were trained to describe somatic sensory stimuli using a standard list of descriptors. This same list was used to describe sensations evoked intraoperatively by thalamic microstimulation. Stimulation sites (n = 216) were defined by location within the area where the majority of cells had a reproducible response to innocuous cutaneous stimulation (core region) or in the cellular area posterior and inferior to the core region (posteroinferior region). 2. TMS-evoked sensations were categorized as paresthetic if the descriptors "tingle," "vibration," or "electric current" were chosen by the patient to describe the sensation and as thermal/pain if the descriptors "cool," "warm," "warm and cool," or "pain" were chosen. Thermal/pain sensations were evoked by stimulation in 82% (9/11) of patients and at 19% of sites studied. These results suggest that thalamic microstimulation can evoke thermal/pain sensations reproducibly across patients. 3. Thermal/pain sensations were evoked more frequently by stimulation at sites in the posteroinferior region (30%) than by stimulation at sites in the core region (5%). Nonpainful thermal sensations composed the majority of thermal/pain sensations evoked by stimulation in both the core (80%) and posteroinferior regions (86%). Sites where stimulation evoked pain and nonpainful cool sensations were found anterior to the area where nonpainful warm sensations were evoked. Thermal/pain sensations were evoked at sites located medially near the border between the core and posteroinferior regions. 4. Radiologic techniques were used to determine the presumed nuclear location of stimulation sites. Thermal/pain sensations were evoked less frequently by stimulation in the part of Vc included in the core region than by stimulation in any of the following: the part of Vc included in the posteroinferior region, ventralis caudalis portae nucleus, ventralis caudalis parvocellularis nucleus, or the white matter underlying the ventral nuclear group. 5. The location of the sensation evoked by stimulation [projected field (PF)] varied widely in size. PFs were categorized as large if they involved more than one part of the body (e.g., face and arm) or if they crossed at least one joint proximal to the metacarpophalangeal joint or to the metatarsophalangeal joint. PFs were more frequently large at sites where thermal/pain sensations were evoked by TMS (33%) than at those where paresthesia were evoked (6%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360717 TI - Motor cortical activity during drawing movements: population representation during sinusoid tracing. AB - 1. Monkeys were trained to trace sinusoids with their index fingers on a planar surface. During this task, both the direction and speed of movement varied continuously. Activity of individual units in the precentral gyrus contralateral to the moving arm was recorded as the task was performed. These cells responded to passive movement of the shoulder and/or elbow. The relation between discharge rate and movement direction for these individual cells could be described with a cosine tuning function. 2. Data recorded as the sinusoid was traced were divided into 100 bins as each cell was studied during the experiment. In each bin, the activity of a particular cell was represented by a vector. The vector ("cell vector") pointed in the direction of finger movement that corresponded to the highest rate of neuronal discharge. This direction, referred to as the preferred direction, corresponded to the peak of the cosine tuning function. The direction of the vector was constant between bins, but the magnitude of this cell's vector was a function of the instantaneous discharge rate. 3. This cell vector is a hypothetical contribution of a single cell to the population response comprised of 554 similarly derived vectors from different cells. The population response was represented as the vector that resulted from forming the sum of the vector contributions from the individual cells. A separate calculation was made for each bin, resulting in 100 population vectors for each sinusoid. 4. Within a given time series of population vectors, their lengths and directions varied in a consistent relation to the tangential velocity of the drawing movement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360718 TI - Neuronal activity in the second somatosensory cortex of monkeys (Macaca mulatta) during active touch of gratings. AB - 1. In penetrations made into the upper bank of the lateral sulcus in two monkeys (Macaca mulatta), cells were isolated from the second somatosensory cortex (SII). During single-cell recordings, animals performed an active touch task in which they rubbed their fingertips over pairs of gratings differing in groove width and indicated which was the smoother surface. Hand motion and downward applied force were measured and recorded during these strokes. 2. In this survey, 151 penetrations provided observations on 352 cells that responded to passive stimulation of the digits or during performance of the active touch task. Consistent with previous reports, receptive fields (RFs) in SII were large, often multi-digit, and frequently included a portion or all of the hand and occasionally the arm. Modality was determined for 92 of 127 fully characterized cells, and included 70 cutaneous, 5 deep, 11 Pacinian corpuscle, and 6 joint cells. Characteristic of SII, modality could not be defined in 35 cells that were unresponsive to passive stimulation or whose responses varied widely over time. 3. Response properties of a subgroup of 79 cells in SII resembled those previously studied in the primary somatosensory cortex (SI) and ventroposterior lateral nucleus of the thalamus (VPL) using identical procedures. Correlation analysis revealed that 29 of these cells, like a portion of cells in SI, responded to changes in groove width independent of force or velocity. This selectivity could be considered a form of feature specificity. 4. In contrast to SI and VPL, transient responses to the fingertips contacting small elevated metal bars, which demarcated the beginning, middle, and end of strokes across the gratings, were seen in a majority of SII cells (109/127). During contact with bars, 89 cells displayed excitatory responses and 20 cells showed suppressed activity. Twelve cells, which responded to bars in isolation from gratings, provided a possible example of increased stimulus selectivity. 5. Passive stimulation failed to activate 16 cells that responded, in some cases differentially to gratings or force, during the task. Responses of nine other cells demonstrated task-dependent modulation in the form of response reduction or enhancement during selected portions of the stroke. In these same cells, response changes did not occur under comparable stimulus conditions in other portions of the stroke that differed only in behavioral context. These types of selective response modulations, not noted in our previous studies of VPL or SI, suggest that mechanisms regulating sensory inputs may affect SII.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360719 TI - Effects of bilateral and unilateral ablation of auditory cortex in cats on the unconditioned head orienting response to acoustic stimuli. AB - 1. Reflexive head orienting responses (ORs) elicited by bursts of wide-band noise were investigated in cats after bilateral or unilateral ablation of the auditory cortex, and the cats' performance was compared with that of control cats. The OR was used as an indication of ability to orient toward the azimuthal direction of a source of sound. 2. To adequately test this ability, a unique combination of stimulus duration and position of the sound source was selected on each trial. Stimulus durations (0.1, 0.3, and 1.5 s) were selected so that the offset of a burst of noise occurred before, during, or after an OR. The stimuli were produced from speakers positioned approximately at the interaural horizontal plane within each quadrant of a cat's auditory field. The ORs were recorded on moving film and analyzed quantitatively. 3. In the control cats, the trajectory of the OR was characterized by a saccadic profile (rapid steplike movement, monophasic velocity, and biphasic acceleration). The accuracy of the OR varied directly with stimulus duration, suggesting that the response was modified by auditory feedback produced by a head movement during the stimulus. Corrective responses executed during long-duration (1.5 s) stimuli reduced residual mean error to < 7 degrees in each of the control animals. The mean error in orientation was smaller for sources located in the frontal sound field than for sources located behind the coronal plane the head (> 90 degrees). When brief (0.1 s) stimuli were presented behind the head, the cats confused back with front directions on most of the trials. 4. Compared with performance in the control cats, bilateral destruction of the auditory geniculocortical system severely impaired a cat's ability to orient consistently and accurately toward a source of sound. Latencies to the onset of ORs were increased, the magnitudes of ORs were reduced, average error in orienting to a sound source was larger under every stimulus duration-source position combination, relatively few corrective responses were executed, and residual mean error was significantly elevated (bilateral = 28.1 degrees; control = 3.1 degrees). Several animals with bilateral lesions also made vertical errors in orienting to azimuthal sources of sound. 5. However, in the bilateral lesion group, ORs were initiated in the correct right or left direction; and, rather than eliminating accurate responses altogether, the lesions reduced the probability of their occurrence. Furthermore, the saccadic profile of the response was preserved, providing evidence that the motor control system for the OR was not perturbed by the bilateral lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360720 TI - Covert orienting of attention in macaques. I. Effects of behavioral context. AB - 1. A task was used by Posner (1980) to measure shifts of attention that occurred covertly, in the absence of an eye movement or other orienting response. This paradigm was used here to assess the nature of covert attentional orienting in monkeys to develop an animal model for neurophysiological studies. Shifts of attention were measurable in monkeys and were consistent across a variety of experimental conditions. 2. The paradigm required that monkeys fixate and release a bar at the appearance of a target, which was preceded by a cue. Reaction times to targets that followed peripheral cues at the same location (validly cued) were significantly faster than those that followed cues in the opposite visual field (invalidly cued). This difference was defined as the validity effect, which as in humans, is used as the measure of a covert attentional shift. 3. When the proportion of validly to invalidly cued targets was decreased, no change was seen in the validity effect of the monkeys. This is in contrast to humans, for whom the ratio of validly to invalidly cued targets affected the magnitude of the validity effect. When 80% of the targets were preceded by cues at the same location, the validity effect was greatest. The effect was reversed when the proportions were reversed. From this result, it is concluded that cognitive processes can affect covert orienting to peripheral cues in humans, whereas in trained monkeys, performance was automatic. 4. To test whether cognitive influences on attention could be demonstrated in the monkey, an animal was taught to use symbolic, foveal signals to covertly direct attention. The magnitude of this validity effect was greater than that obtained with peripheral cues. 5. The effects of motivational and perceptual processes were tested. Although overall reaction times could be modified, the facilitating effects of the cues persisted. This constancy across motivational and perceptual levels supports the notion that the monkeys were performing the task in an automatic way, under the exogenous control of peripheral cues. 6. Most visual cuing has been tested with visual landmarks at the locations of cues and targets. These monkeys were trained with such landmarks, and when tested without them, the attentional effect of the cues was nearly abolished. These data suggest that local visual features can be important for covert orienting. 7. To determine the spatial extent of the effect of the cue, monkeys and humans were tested with four cue-target distances (0-60 degrees).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8360721 TI - Effects of selective attention on spatial form processing in monkey primary and secondary somatosensory cortex. AB - 1. The effects of selective attention were studied in SI and SII cortex of a rhesus monkey trained to perform two tasks, a tactile discrimination task and a visual detection task. In the tactile task, a letter was displayed on a video screen in front of the monkey and the animal was rewarded for responding when the raised letter (6.0 mm letter height) scanning across its finger (15 mm/s) matched the letter on the screen. In the visual task, three illuminated squares were displayed on the screen, and the animal was rewarded for detecting when one of the squares dimmed. The neural responses evoked by the raised letters were recorded continuously while the animal's focus of attention was switched back and forth between the two tasks. 2. Significant differences between the discharge rates evoked by raised letters in the two tasks were observed in approximately 50% of neurons in SI cortex and 80% of neurons in SII cortex. The effects in SII cortex were divided between increased (58%) and decreased (22%) rates. In SI cortex only increased rates were observed. 3. The attentional effects were expressed not only as changes in overall neuronal activity but also as modifications of the form of the responses evoked by the letters. 4. Whether attentional effects were observed depended upon the behavioral relevance of individual letters. During brief periods in the tactile task when a behavioral response could not yield a reward (time-out and reward periods) the neuronal responses were not significantly different from the responses evoked by the same letters during the visual task.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360722 TI - Medical therapeutic strategy of acute cerebral ischaemia in adults. PMID- 8360723 TI - Contribution of computerized tomography to the diagnosis of acute cerebral ischaemia. PMID- 8360724 TI - Magnetic resonance imaging in acute cerebral ischaemia. AB - The frequency of cerebral vascular accidents justifies a rapid evaluation of the patients to distinguish between ischaemia and haematoma. In acute cerebral ischaemia, data from the literature show that magnetic resonance imaging is sensitive early (4th to 6th hours) and anatomically efficient (posterior fossa, brain stem) although it lacks specificity, being based on water movements alone. The most difficult differential diagnosis in the acute phase is bleeding, and in that phase early computerized tomography images are easier to interpret. PMID- 8360725 TI - Epidemiology of stroke. PMID- 8360726 TI - Posterior subscapular approach to the brachial plexus. Report of 102 patients. AB - A 15-year operative experience with 105 posterior subscapular approaches to the brachial plexus in 102 patients is presented. The procedure is indicated in carefully selected cases, especially where the proximal portions of lower spinal nerves are involved. Its main advantage is proximal exposure of the plexus spinal nerves, particularly at an intraforaminal level. The indications in this series were thoracic outlet syndrome (TOS) in 51 carefully selected procedures, brachial plexus tumor involving proximal roots in 22 patients, post-irradiation brachial plexopathy in 14 cases, and proximal traumatic brachial plexus palsy in 18 patients. Thoracic outlet syndrome associated with neurological loss, recurrent TOS after a prior operation, or proximal brachial plexus surgical lesions involving the spinal nerve(s), especially at an intraforaminal level, can be approached advantageously by such a posterior subscapular approach. The technique should also be considered when prior operation, trauma, or irradiation to the neck or anterior chest wall make a posterior exploration of the plexus easier than an anterior one. Anterior exposure of the plexus is the preferable approach for the majority of lesions needing an operation, but the posterior subscapular procedure can be useful in well-selected cases. PMID- 8360727 TI - Centrocentral anastomosis of the proximal nerve stump in the treatment of painful amputation neuromas of major nerves. AB - The term "centrocentral anastomosis" is used to describe the end-to-end connection across interposed nerve grafts between paired fascicular groups of the proximal stump of a severed nerve. In 22 patients harboring a painful terminal neuroma following amputation of a lower limb (20 neuromas on the sciatic nerve and two on the peroneal nerve), a centrocentral anastomosis was performed on the end of the sectioned nerve to treat pain that had not improved with conventional conservative treatment. Follow-up review at 1 year revealed that the typical neuroma pain had disappeared in all cases, although sporadic diffuse pain persisted in four. Where previous phantom sensation was present, no change was observed. The results presented here are consistent with laboratory findings demonstrating the absence of neuroma formation after centrocentral anastomosis. Therefore, this technique is recommended for the treatment of painful amputation neuroma. PMID- 8360728 TI - Short-segment compression instrumentation for selected thoracic and lumbar spine fractures: the short-rod/two-claw technique. AB - The short-rod/two-claw (SRTC) technique of spine instrumentation was recently introduced for the treatment of thoracic and lumbar spine fractures. The use of this technique in 10 patients harboring wedge compression or burst fractures of the thoracic or lumbar spine is described. Of three patients treated with the construct placed in a distraction mode, the average follow-up loss of angle (the difference between the immediate postoperative and follow-up midsagittal angle as measured on x-ray films) was 18.3 degrees. Of the seven patients in whom the instrumentation was placed in a compression mode, the average observed loss of angle at follow-up examination was 1.6 degrees. Two patients had a preoperative scoliotic deformity at the fracture site, and both deformities were exaggerated by the placement of the SRTC technique in compression. Although no patient experienced an adverse outcome and all achieved a solid fusion, the application of the SRTC technique of universal spine instrumentation in distraction was associated with an exaggerated loss of angle. Loss of angle and deformity exaggeration are not desirable and are preventable by strict patient selection and by applying the construct in a compression mode. It is emphasized that few patients are candidates for this form of instrumentation. When applicable, however, the advantages of decreased pain and stiffness and the elimination of the need for instrumentation removal make the SRTC and related short-segment techniques desirable alternatives to traditional methods of spinal fixation. PMID- 8360729 TI - Magnetic resonance imaging documentation of coexistent traumatic locked facets of the cervical spine and disc herniation. AB - The coexistence of traumatic locked facets of the cervical spine and a herniated disc is not well described. The authors present a series of patients with traumatic locked facets who demonstrated a high incidence of associated disc herniation documented on magnetic resonance (MR) imaging. Thirteen patients with either unilateral (four cases) of bilateral (nine cases) locked facets of the cervical spine were analyzed retrospectively. Immediate closed reduction using traction and/or manipulation was attempted in the first nine cases treated and was successful in only three; however, the procedure was abandoned in three cases due to deterioration in the patient's clinical status. In the subsequent four patients, an MR image was obtained prior to attempts at closed reduction. All patients underwent MR imaging of the cervical spine. Of eight consecutive cases treated at the University of Michigan, frank disc herniation with fragmented disc in the canal was found in five while pathological disc bulging was found in the other three. All five cases contributed by other institutions had concurrent disc herniation. This series illustrates the importance of using MR imaging to document the presence of a herniated disc during the initial evaluation of a patient with traumatic locked facets of the cervical spine and prior to attempted reduction of the locked facets. Experience indicates that closed reduction of facet dislocation associated with disc rupture may result in increased spinal cord compression and neurological deficit. If a herniated disc is discovered, anterior discectomy and fusion would be favored as the initial therapy over attempts at closed reduction or operative posterior reduction. PMID- 8360730 TI - Reflex variability in selective dorsal rhizotomy. AB - The variability of reflex responses during selective dorsal rhizotomy was studied in eight children between the ages of 3 and 7 years. For a given dorsal root or rootlet, the electrical reflex threshold and response varied considerably when observed over several minutes. Changes in electrode pressure, mechanical dissection of the root, and reflex spatial facilitation were all found to contribute to the variability. Even when electrode pressure was held constant, intrinsic spinal cord reflex variability substantially weakened the predictability of the intraoperative selection method used during this surgery. PMID- 8360731 TI - The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. AB - Animal research suggests that moderate therapeutic hypothermia may improve outcome after a severe head injury, but its efficacy has not been established in humans. The authors randomly assigned 40 consecutively treated patients with a severe closed head injury (Glasgow Coma Scale score 3 to 7) to either a hypothermia or a normothermia group. Using cooling blankets and cold saline gastric lavage, patients in the hypothermia group were cooled to 32 degrees to 33 degrees C (brain temperature) within a mean of 10 hours after injury, maintained at that temperature for 24 hours, and rewarmed to 37 degrees to 38 degrees C over 12 hours. Patients in the normothermia group were maintained at 37 degrees to 38 degrees C during this time. Deep-brain temperatures were monitored directly and used for all temperature determinations. Intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolic rate for oxygen (CMRO2) were measured serially for all patients. Hypothermia significantly reduced ICP (40%) and CBF (26%) during the cooling period, and neither parameter showed a significant rebound increase after patients were rewarmed. Compared to the normothermia group, the mean CMRO2 in the hypothermia group was lower during cooling and higher 5 days after injury. Three months after injury, 12 of the 20 patients in the hypothermia group had moderate, mild, or no disabilities; eight of the 20 patients in the normothermia group had improved to the same degree. Both groups had a similar incidence of systemic complications, including cardiac arrhythmias, coagulopathies, and pulmonary complications. It is concluded that therapeutic moderate hypothermia is safe and has sustained favorable effects on acute derangements of cerebral physiology and metabolism caused by severe closed head injury. The trend toward better outcome with hypothermia may indicate that its beneficial physiological and metabolic effects limit secondary brain injury. PMID- 8360732 TI - Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. AB - Recent experimental studies have demonstrated that mild hypothermia at about 34 degrees C can be effective in the control of intracranial hypertension. A randomized controlled study of mild hypothermia was carried out in 33 severely head-injured patients. All patients fulfilled the following criteria: 1) persistent intracranial pressure (ICP) greater than 20 mm Hg despite fluid restriction, hyperventilation, and high-dose barbiturate therapy; 2) an ICP lower than the mean arterial blood pressure; and 3) a Glasgow Coma Scale score of 8 or less. The patients were divided into two groups: one received mild hypothermia (16 patients) and one served as a control group (17 patients). Mild hypothermia significantly reduced the ICP and increased the cerebral perfusion pressure. Eight patients (50%) in the hypothermia group and three (18%) in the control group survived (p < 0.05), while five (31%) in the hypothermia group and 12 (71%) in the control group died of uncontrollable intracranial hypertension (p < 0.05). In five patients in the hypothermia group, cerebral blood flow was measured by the hydrogen clearance method and arteriojugular venous oxygen difference was evaluated before and during mild hypothermia. Mild hypothermia significantly decreased the cerebral blood flow, arteriojugular venous oxygen difference, and cerebral metabolic rate of oxygen (p < 0.01). The results of this preliminary investigation suggest that mild hypothermia is a safe and effective method to control traumatic intracranial hypertension and to improve mortality and morbidity rates. PMID- 8360733 TI - A clinical study of the relationship of timing to outcome of surgery for ruptured cerebral aneurysms. A retrospective analysis of 1622 cases. AB - Between 1980 and 1987, 1622 patients with angiographically verified ruptured cerebral aneurysms were admitted within 7 days after subarachnoid hemorrhage. A retrospective analysis evaluated both the timing of surgery in operative patients and the status of nonsurgical patients. The patients' clinical grade according to the Hunt and Hess classification was assessed at admission, and a comparative analysis of outcome was carried out for each grade in relation to time of surgery: those operated on from Day 0 to 3 and those undergoing surgery on Day 4 or later. Among nonsurgical cases, fatal rebleeding occurred in 105 cases and fatal vasospasm in 69 cases. These nonsurgical cases were divided into one of two groups, either an early- or a late-management group, and the outcome of each group was analyzed by clinical grade. The mortality rates in the early-surgery groups were higher than in the late-surgery groups, especially in Grade V, in which the rate was significantly different. However, with the 174 nonsurgical patients included in these management results, marked differences in mortality rates disappeared except in Grade V, which failed to show statistical significance. A higher rate of good recovery among Grade III patients receiving early surgery shifted significantly in the early-management group. The results suggest that the timing of surgery in clinical Grade I or II patients is not a major factor; however, early surgery appears to be beneficial in Grade III and IV patients. The incidence of rebleeding in the early- and late-management groups was 2.7% and 9.5%, respectively. PMID- 8360734 TI - Anterior communicating artery collateral flow protection against ischemic change during carotid endarterectomy. AB - The purpose of this study was to determine whether preoperative angiographic patterns of collateral cerebral blood flow correlate with protection against intraoperative electroencephalographic (EEG) evidence of cerebral ischemia caused by carotid artery cross-clamping during carotid endarterectomy. Previous studies have shown that contralateral carotid artery occlusion and intracranial stenoses are associated with cerebral ischemia during carotid endarterectomy; however, the angiographic collateral flow patterns associated with cerebral ischemia have not been identified. This paper reports a retrospective study of 67 patients who underwent two- to four-vessel cerebral angiography followed by carotid endarterectomy with 16-channel EEG monitoring. The angiograms were reviewed for extracranial occlusive disease and collateral flow patterns, and the EEG recordings were analyzed for ischemic changes during carotid artery cross clamping. Statistical analysis was by Fisher's exact test. Cross-filling of the anterior and middle cerebral arteries from the contralateral carotid artery through the anterior communicating artery correlated with a decreased incidence of EEG ischemic changes. Only 21% of patients with this collateral flow pattern showed ischemic changes compared to 50% of patients without this pattern (p < 0.03). Three angiographic findings occurring in combination on the side contralateral to surgery correlated with EEG ischemia: 1) occlusion of the contralateral internal carotid artery (five of seven or 71%, p < 0.03); 2) collateral flow from the external carotid circulation to the internal carotid circulation via the ophthalmic artery; and 3) collateral flow from the posterior circulation to the contralateral anterior circulation via the posterior communicating artery. The data presented here corroborate the correlation between contralateral carotid artery occlusion and cerebral ischemia during carotid endarterectomy. They also demonstrate that cross-filling of the anterior and middle cerebral arteries by the contralateral carotid artery protects against such ischemia. This collateral flow may serve as an indicator of tolerance to carotid artery cross-clamping. PMID- 8360735 TI - Evaluation of pressure changes in feeding arteries during embolization of intracerebral arteriovenous malformations. AB - The pressure in 47 arteries feeding 21 arteriovenous malformations (AVM's) was investigated during transarterial embolization using a Tracker-18 microcatheter. On average, systolic pressure increased by 22 mm Hg. In AVM's with single or few feeders, embolization was usually achieved well; in contrast, giant AVM's with multiple feeders and a large arteriovenous shunt were poorly embolized. However, large AVM's with well-demarcated components may be reduced by embolization to an appropriate size for surgery or stereotactic radiation therapy. It was found that the feeding artery pressure increased significantly more in well-embolized than in poorly embolized cases. Measurements of the feeding artery pressure clarified the hemodynamics of AVM's and facilitated more successful embolization. PMID- 8360736 TI - Percutaneous lateral cervical cordotomy: target localization with water-soluble contrast medium. AB - Water-soluble intrathecal contrast material was used for radiographic identification of the cord target in 13 patients undergoing percutaneous lateral cervical cordotomy. Adequate visualization of the dentate ligament, considered essential for successful placement of the electrode, was achieved in seven cases. In the remaining six patients, four with suboptimal definition and two with nonvisualization of the ligament, an additional injection of contrast medium using a modified coaxial needle system outlined the entire thickness of the cervical cord. This technique improved needle-tip positioning in relation to the cord and resulted in successful surgery in all six patients. PMID- 8360737 TI - Intraoperative identification of motor areas of the rhomboid fossa using direct stimulation. AB - Intraoperative electrical identification of motor areas within the floor of the fourth ventricle was successfully carried out in a series of 10 patients with intrinsic pontine lesions and lesions infiltrating the brain stem. Direct electrical stimulation was used to identify the facial colliculus and the hypoglossal triangle before the brain stem was entered. Multichannel electromyographic recordings documented selective stimulation effects. The surgical approach to the brain stem was varied according to the electrical localization of these structures. During removal of the lesion, functional integrity was monitored by intermittent stimulation. In lesions infiltrating the floor of the fourth ventricle, stimulation facilitated complete removal. Permanent postoperative morbidity of facial or hypoglossal nerve dysfunction was not observed. Mapping of the floor of the fourth ventricle identifies important surface structures and offers a safe corridor through intact nervous structures during surgery of brain-stem lesions. Reliable identification is particularly important in mass lesions with displacement of normal topographical anatomy. PMID- 8360738 TI - Urinary epidermal growth factor in patients with gliomas: significance of the factor as a glial tumor marker. AB - Epidermal growth factor (EGF) content in urine from patients with glial tumors was examined by radioimmunoassay techniques with labeled human EGF and its rabbit EGF polyclonal antibody. There was no cross-reaction with transforming growth factor-alpha, which has a common receptor with EGF. Forty glial tumors were divided into three groups according to the clinical stage: Samples from Group A patients were obtained before therapy and/or after biopsy; in these patients a large volume of tumor was apparent on computerized tomography (CT). Group B samples were obtained after gross total removal of the tumor and/or chemo- and radiation therapy; these patients showed a small volume of residual tumor on CT. Samples from Group C patients were obtained after gross tumor total removal and/or chemo- and radiation therapy; no tumor was detected on CT scans in these patients. Urinary EGF levels in Group A samples were statistically significantly higher than in samples from healthy individuals (p < 0.001), Group B patients (p < 0.10), and Group C patients (p < 0.02). In addition, high-grade glial tumors in Group A cases showed a significantly higher level of urinary EGF than low-grade tumors in Group A patients (p < 0.05), or patients with meningioma (p < 0.02), metastatic brain tumor (p < 0.05), and cerebral infarction (p < 0.001). Longitudinal changes of urinary EGF levels in glioma patients mostly synchronized with the clinical course and therapeutic interventions. Therefore, urinary EGF, as a glial tumor marker, may be of practical value for diagnosing a malignant glioma and evaluating for the efficacy of chemo- and radiation therapy. PMID- 8360739 TI - A comparison of the protective effect of dexamethasone to other potential prophylactic agents in a neonatal rat model of cerebral hypoxia-ischemia. AB - It has recently been reported that pretreatment with a single dose of dexamethasone (0.1 mg/kg) 24 hours before hypoxia in 7-day-old rat pups is protective against an hypoxic-ischemic insult (unilateral carotid artery occlusion followed by 3 hours of hypoxia in 8% O2). The authors now examine whether pretreatment 6 hours before insult is equally effective and compare other agents potentially suitable for prophylaxis in neonatal hypoxia-ischemia, including the calcium antagonists flunarizine (30 mg/kg pretreatment), nimodipine (0.5 mg/kg pretreatment), and the 21-aminosteroid U-74389F (10 mg/kg pre- and posttreatment). For each active agent, there was also a vehicle-treated control group. Comparison of the mean area of ipsilateral infarction on brain coronal sections showed that there was no statistically significant difference between the various control groups (mean area of infarction 66% +/- 4%). Pretreatment with dexamethasone 6 hours prior to hypoxia offered complete protection with no infarction. A beneficial effect was seen following pretreatment with flunarizine (mean area of infarction 33.6% +/- 7.8%), although this degree of damage was still significantly different from that seen with dexamethasone pretreatment. Pretreatment with nimodipine or U-74389F offered no protection (mean area of infarction 77.5% +/- 4% and 59% +/- 10%, respectively). Unlike findings in adult animals and clinical studies, the current studies show that dexamethasone may have a role in the treatment of neonatal hypoxia-ischemia and deserves reappraisal. PMID- 8360740 TI - Traumatic brain injury, hemorrhagic shock, and fluid resuscitation: effects on intracranial pressure and brain compliance. AB - Intracranial hypertension following traumatic brain injury is associated with considerable morbidity and mortality. Hemorrhagic hypovolemia commonly coexists with head injury in this population of patients. Therapy directed at correcting hypovolemic shock includes vigorous volume expansion with crystalloid solutions. It is hypothesized that, following traumatic brain injury, cerebrovascular dysfunction results in rapid loss of brain compliance, resulting in increased sensitivity to cerebrovascular venous pressure. Increased central venous pressure (CVP) occurring with vigorous crystalloid resuscitation may therefore contribute to the loss of brain compliance and the development of intracranial hypertension. The authors tested this hypothesis in miniature swine subjected to traumatic brain injury, hemorrhage, and resuscitation. Elevated CVP following resuscitation from hemorrhage to a high CVP significantly worsened intracranial hypertension in animals with concurrent traumatic brain injury, as compared to animals subjected to traumatic brain injury alone (mean +/- standard error of the mean: 33.0 +/- 2.0 vs. 20.0 +/- 2.0 mm Hg, p < 0.05) or to animals subjected to the combination of traumatic brain injury, hemorrhage, and resuscitation to a low CVP (33.0 +/- 2.0 vs. 24.0 +/- 2.0 mm Hg, p < 0.05). These data support the hypothesis that reduction in brain compliance can occur secondary to elevation of CVP following resuscitation from hemorrhagic shock. This may worsen intracranial hypertension in patients with traumatic brain injury and hemorrhagic shock. PMID- 8360741 TI - Clival chordoma associated with pathological laughter. Case report. AB - The case of a 40-year-old man with a clival chordoma who presented with symptoms of pathological laughter and left sixth cranial nerve paresis is reported. Laughing and talking during sleep were noted on polygraphic and videotape recordings of nocturnal sleep. Selective disorganization of sleep was observed, with laughing facial expressions and a lack of muscular atonia. The tumor developed in the prepontine cistern, compressing the pontomesencephalic structures backward and involving the upper clivus and the left cavernous sinus. No recurrence of laughter attacks were noted after total removal of the tumor. The sleep patterns observed were similar to those of experimental animals with lesions of the peri-alpha locus ceruleus. The importance of uncontrolled laughter as a sign of a ventral brain-stem mass is emphasized. PMID- 8360742 TI - Spontaneous thrombosis of posterior cerebral artery aneurysm with angiographic reappearance. Case report. AB - The case is presented of a 23-year-old man suffering ischemic brain infarction from spontaneous thrombosis of a left posterior cerebral artery P1-P2 junction aneurysm. Vasospasm and/or partial parent vessel occlusion were documented by magnetic resonance (MR) imaging and angiography. Repeat cerebral angiography and MR imaging 3 months later revealed patency of the posterior cerebral artery and luminal filling of a 1-cm fusiform aneurysm, which was successfully trapped at surgery. PMID- 8360743 TI - Supraclinoid internal carotid artery fenestration with an associated aneurysm. Case report. AB - The case of an aneurysm occurring at the site of fenestration of the supraclinoid portion of the left internal carotid artery (ICA) is reported. A 37-year-old woman presenting with subarachnoid hemorrhage was found to have bilateral ICA aneurysms at the level of the posterior communicating arteries (PCoA's). The patient underwent right-sided craniotomy with uneventful clipping of the right PCoA aneurysm, and attempted clip placement on the contralateral left ICA aneurysm. The follow-up angiogram revealed a residual dome on the left ICA aneurysm, which was noted to originate at the proximal end of a fenestration of the left supraclinoid ICA. This represents the third reported case of fenestration of the intracranial ICA associated with an aneurysm. Intracranial artery fenestrations and their embryological origins are also reviewed. PMID- 8360744 TI - Spinal epidural leiomyoma occurring in an HIV-infected man. Case report. AB - A case of spinal epidural leiomyoma is reported in a 52-year-old man infected with the human immunodeficiency virus (HIV). The tumor arose in the epidural region at the T-3 vertebral level, and the patient presented with radicular pain in the right T-3 dermatome. While soft-tissue tumors such as Kaposi's sarcoma and lymphomas have been well documented in association with HIV infection, this is the first reported case of primary spinal leiomyoma. Isolated cases of leiomyomas and leiomyosarcomas in unusual locations have been reported, notably in pediatric HIV-positive patients, perhaps indicating a causal relationship. This case may represent further evidence of such an association. PMID- 8360745 TI - Spinal cord infarction associated with primary antiphospholipid syndrome in a young child. Case report. AB - Antiphospholipid antibodies have been reported to occur in ischemic stroke patients, but there have been no previous reports linking these antibodies to spinal cord infarction. A case of spinal cord infarction associated with primary antiphospholipid syndrome in a 6-year-old boy is reported. Magnetic resonance imaging clearly demonstrated marked swelling of the thoracolumbar spinal cord with gadolinium-diethylenetriamine pentaacetic acid enhancement at an acute stage, followed later by cord atrophy. Serological study disclosed positive lupus anticoagulant and immunoglobulin G anticardiolipin antibody. It is suggested that the role of antiphospholipid antibodies as an etiological factor for spinal cord ischemia should be recognized among causes that might have been categorized as either spontaneous spinal cord infarction or myelitis. PMID- 8360746 TI - Hemodynamic activity associated with a paraganglioma of the cauda equina. Case report. AB - A 53-year-old man presented with a paraganglioma of the cauda equina that caused significant hemodynamic instability during removal. The clinical implications of this phenomenon are discussed. PMID- 8360747 TI - Pigmented villonodular synovitis of the spine. Case report. AB - Pigmented villonodular synovitis commonly occurs in synovial joints of the appendicular skeleton, but rarely affects the synovial joints of the spine. It has both neoplastic and benign features, and the etiology is thought to be posttraumatic. The case of a young man presenting with paraparesis and a large thoracic lesion is reported. PMID- 8360748 TI - Cosmetic mastoidectomy for the combined supra/infratentorial transtemporal approach. Technical note. AB - The authors describe a cosmetic mastoidectomy technique for use when performing a combined supra/infratentorial craniotomy and transtemporal exposure. The technique involves a single temporal suboccipital bone flap and cosmetic mastoidectomy, removing the outer table of bone for later replacement. Replacement of the outer table of mastoid bone enables tamponade of a fat graft against the dura to reduce the risk of postoperative cerebrospinal fluid leaks. The technique has been performed in eight patients treated for petroclival meningiomas with excellent cosmetic results. PMID- 8360749 TI - A new brain retractor. Technical note. AB - A new brain retractor is presented that can be applied easily and safely from any direction. It is particularly useful in the evacuation of intracerebral hematomas. PMID- 8360750 TI - The Vanderbilt University neurosurgical heritage. AB - The Vanderbilt University Hospital heritage was influenced by the excellence of the Johns Hopkins era--by Osler, Halsted, Cushing, Brooks, and many others. Upon this strong origin, the neurosurgery department was built by Cobb Pilcher and perpetuated by William F. Meacham. PMID- 8360751 TI - Cerebral hemicorticectomy for epilepsy. PMID- 8360752 TI - Magnetic resonance imaging surveillance. PMID- 8360753 TI - Doppler ultrasound prediction of delayed ischemia. PMID- 8360754 TI - Assuring institutional control of private duty personnel. PMID- 8360755 TI - Mothers who use nurse midwives have shorter hospital stays and fewer cesarean sections and episiotomies. PMID- 8360756 TI - Outcome evaluation: frustration or fertile field? PMID- 8360757 TI - The head nurse role in redesign. AB - As administrators review how best to meet patient's needs and redesign patient care givers' job content, as well as introduce multiskilled workers to the patient care unit, the head nurse role must be reviewed and revamped at the same time. The author describes the experiences of two different institutions in overloading the head nurses with reporting relationships that they were ill equipped to supervise. The solution in both institutions was the same, and emphasizes the need for interactive planning for these complex and interdependent models. PMID- 8360758 TI - The chief nurse officer as a board member: representation and compensation. PMID- 8360759 TI - Accounting for contributions. An update. PMID- 8360760 TI - A competency achievement orientation program. Professional development of the home health nurse. AB - One of the vital components to the assurance of quality nursing care is a comprehensive orientation program. The concept of a competency achievement program facilitates the development of independent practice and judgment skills on the part of today's home healthcare nurse. The authors discuss one agency's program to meet the needs of newly employed registered nurses. PMID- 8360761 TI - Developmental levels of interdisciplinary collaborative practice committees. AB - Establishing interdisciplinary collaborative practice committees has and will be a prime strategy in healthcare. Evaluating the functioning, progress, and outcomes of these committees is important. Defining a mechanism to evaluate interdisciplinary collaborative practice committees should be beneficial. The author presents an easy evaluation tool that can determine the level and functioning of interdisciplinary collaborative practice committees. PMID- 8360762 TI - Experiences, events, people. Do they influence the leadership style of nurse executives? AB - Nurse executives play a key role in healthcare organizations. This study asked nurse executives whether there were particular experiences, events, or persons that influenced their leadership style. The answers to this question provide guidance for nurses who aspire to this role. Nurse administrators, leaders, and educators are in pivotal positions to influence the development of leadership in others. PMID- 8360764 TI - Unique AIDS treatment facility. PMID- 8360763 TI - Sustaining work redesign innovations through shared governance. AB - Organizational change, in the form of work redesign, is widespread in hospitals across the country. How can the resulting patient-focused care models be sustained when "sustaining" means continuously changing and improving? The authors describe one hospital's use of a multidisciplinary shared governance system to provide the structure and process support for the innovative changes initiated by work redesign. PMID- 8360765 TI - Strategic planning. A practical approach. AB - A successful organization, whether a corporation or a department within that corporation, will, in most instances, have a plan, a blueprint for action, that establishes goals and a direction for the future. The author outlines initial and subsequent efforts of the department of nursing at a large military medical center to establish an annual strategic planning conference and to develop, implement, and maintain a department of nursing strategic plan. PMID- 8360766 TI - Research or quality improvement?. Making the decision. AB - Deciding if a project is one of research or quality improvement is a dilemma frequently faced by nursing administrators. Guidelines have been established to help administrators and practitioners overcome this dilemma and, at the same time, consider the rights and responsibilities of the patient, the hospital, and the investigator. PMID- 8360767 TI - A cost-benefit analysis of shared governance. AB - Shared governance is one of several strategies promoted by and to nurse executives as critical to retention of professional nurses and important in maintaining quality of care. Thus far, few studies have examined the various financial aspects of this type of decision-making structure. This article identifies a framework for cost analysis and reports the cost-benefit relationship of implementing a shared governance model over a 5-year period. PMID- 8360768 TI - Nurse staff planning under conditions of a nursing shortage. AB - The shortage of qualified nurses presents some important managerial challenges for the hospital administrator. Nurse work force management has often been described as a three-phase planning and control process consisting of staffing, scheduling, and allocation. In this research study, the authors present a research methodology for improving the staffing phase of the process. Specifically, a nurse staffing model was developed as a means of improving the nurse staffing process for a 700-bed, nonprofit hospital. PMID- 8360770 TI - Alphabetical list of consultants and consulting firms. PMID- 8360769 TI - The effective use of consultants. AB - Successful consultation between nurse administrators and management consultants requires developing a good working relationship and effectively managing the consultation process. The authors describe a four-phase consultation process from the perspective of both the manager and the consultant, identifying the critical steps and behaviors at each phase that promote a successful consultation. PMID- 8360771 TI - Minding the gap. PMID- 8360772 TI - Corticosterone enhances the zinc and interleukin-6-mediated induction of metallothionein in cultured rat hepatocytes. AB - The regulation of metallothionein induction in cultured rat hepatocytes was investigated with Zn, hormones, cytokines and either the synthetic glucocorticoid, dexamethasone, or the endogenous rat glucocorticoid, corticosterone. A concentration-dependent increase was seen with Zn (two- to fivefold increase in 24 h, Zn 10-50 mumol/L). Dexamethasone at 1 mumol/L increased metallothionein synthesis by fourfold that of the controls. Maximal metallothionein concentrations of 17-fold the control value were seen with 50 mumol/L Zn and 1 mumol/L dexamethasone. Interleukin-6 (1 x 10(5) U/L) alone did not induce metallothionein but increased it 35-65% with Zn+dexamethasone. Like dexamethasone, corticosterone had a dose dependent effect on metallothionein and synergy with Zn and Zn+interleukin-6. Dexamethasone was approximately 100 times more potent than corticosterone at 10-100 mumol/L. Physiological concentrations of corticosterone (1 mumol/L) when added alone, with Zn (10 mumol/L), and with Zn+interleukin-6 resulted in inductions of 2.2, 5.0 and 7.4-fold above the control cultures. Glucagon (1 mumol/L) had no independent effect but increased metallothionein by 31% and 33% with Zn(10 mumol/L)+dexamethasone (1 mumol/L) and Zn-dexamethasone+interleukin-6, respectively. There was no accumulation of metallothionein with interleukin-1 beta, tumor necrosis factor alpha or interferon gamma (1 x 10(5) U/L) alone, but interleukin-1 beta and tumor necrosis factor alpha enhanced the response obtained with Zn+dexamethasone with and without interleukin-6. Insulin (100 U/L) alone, caused metallothionein accumulation and further enhanced the response seen with Zn+dexamethasone+interleukin-6+glucagon. No additional enhancement was seen with interleukin 1 beta+tumor necrosis factor alpha+interferon. The results demonstrate that concentrations of corticosterone in rats with experimental inflammation facilitate metallothionein induction with Zn and interleukin 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360773 TI - Preweaning diet affects bile lipid composition and bile acid kinetics in infant baboons. AB - We tested, with 14-wk-old baboons before weaning, the hypothesis that bile acid metabolism is differentially affected by breast feeding or by feeding formulas with a high polyunsaturated:saturated fatty acid ratio or with a low ratio, similar to that of breast milk. Bile lipid content, bile acid pool size, fractional turnover rate, synthetic rate and conjugate composition were measured in a single bile sample 9 d after an injection on d 1 of a mixture of [14C]cholic and [14C]chenodeoxycholic acids and an injection of a mixture of [3H]cholic acid and [3H]chenodeoxycholic acid on d 8. The principal biliary bile acid was chenodeoxycholic acid. The only difference in chenodeoxycholic acid metabolism among the infant diet groups was a lower chenodeoxycholic acid synthetic rate in baboons fed the low polyunsaturated:saturated formula compared with those fed the high polyunsaturated:saturated formula or breast-fed. Cholic acid metabolism was significantly affected by infant diet: breast-fed infants had a smaller cholic acid pool size, lower cholic acid percentage of total bile acids, higher cholic acid glycine:taurine conjugate ratio and larger cholic acid fractional turnover rate than formula-fed animals. The polyunsaturated:saturated fatty acid ratio in the formulas did not significantly affect these variables. These results show that differences in bile acid metabolism between breast- and formula-fed infant baboons are limited principally to cholic acid. These differences likely are due to factors other than fatty acid saturation. PMID- 8360774 TI - Selenium deficiency suppresses the S-glutathiolation of carbonic anhydrase III in rat hepatocytes under oxidative stress. AB - To examine the modification of reactive sulfhydryls of carbonic anhydrase III (CA III), hepatocytes were prepared by collagenase perfusion from Se deficient and Se adequate male Sprague-Dawley rats. After 24 h in culture, hepatocytes were treated for 15-30 min with one of two oxidative stressors, t-butyl hydroperoxide (t-BuOOH) or menadione. Modification of CA III was measured by isoelectric focusing/immunoblotting. Formation of glutathione disulfide (GSSG) during oxidative stress was markedly less in hepatocytes of Se-deficient rats than in those of Se-adequate rats. During treatment with t-BuOOH, GSSG formation in hepatocytes from Se-adequate rats reached a maximum at 3 min, and then GSSG was gradually reduced to glutathione. After menadione treatment, intracellular GSSG irreversibly increased in hepatocytes of Se-adequate rats but not in those of Se deficient rats. A modification of CA III that was reversible by dithiothreitol treatment concurred with the formation of GSSG during treatment with either t BuOOH or menadione. Although modification of CA III occurred in hepatocytes from Se-deficient rats, the extent of modification was significantly less than in Se adequacy, and the modification was less reversible by dithiothreitol than in hepatocytes from Se-adequate rats. Selenium deficiency may be useful in examining the importance of modification of specific proteins subjected to oxidative stress. PMID- 8360775 TI - N-(4-hydroxyphenyl)retinamide (fenretinide) induces retinol-binding protein secretion from liver and accumulation in the kidneys in rats. AB - The chemopreventive retinoid N-(4-hydroxyphenyl)retinamide (HPR) depresses serum retinol and retinol-binding protein (RBP) concentrations. To study long-term effects of HPR on serum proteins, rats were fed a control diet or a diet containing HPR (737 mumol/kg diet) for 14 d. Serum retinol and RBP of HPR-treated rats decreased to 42 and 41%, respectively, of initial concentrations. Transthyretin, albumin and transferrin did not differ between treatments. Previous studies found that HPR decreased secretion of the retinol-RBP complex into plasma. To investigate acute effects of HPR on RBP metabolism, vitamin A deficient rats were injected with HPR (51 mumol/kg body wt), retinol (0.52 mumol/rat) or Tween carrier only. Liver RBP concentrations in HPR- and retinol treated rats were 45 and 18%, respectively, of concentrations in Tween-treated rats, indicating rapid RBP secretion. Tween- and HPR-treated rats maintained relatively constant serum RBP concentrations, whereas retinol-replete rats had 12 fold higher serum RBP after 150 min. Rats treated with HPR and rats treated with retinol had 29- and eightfold higher kidney RBP concentrations, respectively, than Tween-treated rats, indicating rapid clearance of RBP from plasma. We conclude that HPR affects RBP metabolism by inducing secretion of liver RBP into the bloodstream and rapid RBP accumulation in the kidney. PMID- 8360776 TI - Dietary chromium supplementation with or without somatotropin treatment alters serum hormones and metabolites in growing pigs without affecting growth performance. AB - Twenty-four castrated male pigs were used in a 2 x 2 treatment array to determine the main effects of and interactions between dietary chromium supplementation and pituitary porcine somatotropin (ppST) administration on growth performance and serum hormone and metabolite concentrations. The treatments were 1) control (basal diet); 2) chromium (basal diet+300 micrograms/kg diet added trivalent chromium as chromium picolinate); 3) ppST (100 micrograms/(kg body wt.d); and 4) chromium+ppST. Treatments were administered when pigs weighed between 30 and 60 kg. Blood was collected when pigs weighted 45 and 60 kg. All pigs treated with ppST exhibited improvements in growth performance (P < 0.05). Pigs given chromium showed no improvements in growth rate, feed efficiency or composition of gain. Measurements at 60 kg body weight revealed that ppST increased the cholesterol:HDL cholesterol ratio (P < 0.05). Chromium lowered serum insulin and glucose concentrations relative to controls (P < 0.05) and normalized the increase in glucose and insulin resulting from ppST treatment. No ppST x chromium interactions were noted, suggesting these changes in glucose and insulin metabolism are exerted through different mechanisms. These results indicate that chromium does not affect growth performance of young growing pigs. Chromium does normalize altered hormone and metabolite concentrations resulting from ppST treatment. PMID- 8360778 TI - Medium-chain fatty acid oxidation in colostrum-deprived newborn piglets: stimulative effect of L-carnitine supplementation. AB - To investigate the role of L-carnitine in medium-chain fatty acid (MCFA, fatty acids with 6-12 carbons) metabolism, 16 newborn pigs were fitted with umbilical arterial catheters. Pigs were placed in respiration chambers, and [1-14C]MCFA were infused for 9-12 h providing energy equivalent to 50-175% of the animals' metabolic rate. After 5-7 h (carnitine-free infusion period) of MCFA infusion, a primed (12.5, 25 or 50 mumol) co-infusion of L-carnitine [5, 10 or 20 mumol/(h.kg0.75), respectively] was started and maintained for 4-5 h (carnitine infusion period). The fatty acid oxidation rate (MCFA-derived CO2/total CO2 x 100) was calculated based on the specific radioactivity of expired CO2 (measured per 20-min interval) and the specific radioactivity of the MCFA infused. A single pool exponential curve was fitted to the fatty acid oxidation rate of the carnitine-free infusion period and was extrapolated to the carnitine infusion period. For each piglet, the average difference between fatty acid oxidation rate during the carnitine infusion period and the extrapolated curve was calculated and tested for significance using a t test. Under steady state conditions, MCFA oxidation accounted for 40% of MCFA infused. Carnitine, independent of the level, increased the fatty acid oxidation rate by as much as 20% if the energy provided as MCFA exceeded 50% of the metabolic needs of the pig (P < 0.01), and the response above 50% was proportional to the relative rate of fatty acid infusion (increase in fatty acid oxidation rate = -3.9 + 0.07 x infusion rate, r0.76).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360777 TI - Alpha-keto and alpha-hydroxy branched-chain acid interrelationships in normal humans. AB - Plasma concentrations of the branched-chain amino acids leucine, isoleucine and valine, and those of leucine's and isoleucine's transamination products alpha ketoisocaproic acid (KICA) and alpha-keto-beta-methylvaleric acid (KMVA), respectively, are known to increase after a protein meal or during extended fasting, but little or no increase in the concentration of valine's transamination product, alpha-ketoisovaleric acid (KIVA), has been observed under these conditions. To determine whether this could be explained by the conversion of KIVA to its alpha-hydroxy analogue, we measured the plasma concentrations of KICA, KMVA and KIVA, as well as their alpha-hydroxy analogues [alpha hydroxyisocaproic acid (HICA), alpha-hydroxy-beta-methylvaleric acid (HMVA) and alpha-hydroxyisovaleric acid (HIVA)], in normal volunteers immediately after a protein meal or during a 60-h fast. We also determined the oxidoreduction equilibrium constants for HIVA/KIVA and HICA/KICA and their extent of plasma protein binding. In subjects in the postabsorptive state, the plasma concentrations of KICA and KMVA were 100 times those of HICA and HMVA, whereas that of KIVA was only twice that of HIVA. Shortly after a protein meal, KICA and KMVA concentrations increased significantly by 30 and 60%, respectively, whereas that of KIVA decreased by 25% (P < 0.05). HICA, HMVA and HIVA concentrations did not change. During prolonged fasting the plasma concentrations of all six metabolites increased gradually. The high plasma keto/hydroxy acid ratios were not related to their K(eq), which favored alpha-hydroxy analogue formation. The reduction of the branched-chain alpha-keto acids to their alpha-hydroxy analogues seems to take place too slowly to attain thermodynamic equilibrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360779 TI - Time after feeding and dietary arginine deficiency alter splanchnic and hepatic amino acid flux in rats. AB - The effect of an arginine-deficient diet containing 3.4% glutamate on net flux of amino acids across the portal-drained viscera and liver was studied in rats at 0, 1 or 2 h after a meal and compared with that in arginine-fed controls. Net portal drained viscera flux for most amino acids was greater in the fed state compared with the postabsorptive state except for glycine and cystine, which did not change, and methionine, which declined. Net amino acid recovery in portal blood 2 h after feeding compared with amounts consumed was highest for alanine (17.3%); recovery of other amino acids ranged from 5.6 to 15.3%. No net portal-drained viscera recovery of consumed cystine was observed. For the branched-chain and aromatic amino acids, methionine, threonine, histidine and lysine, net hepatic uptake was nearly equal to net portal-drained viscera absorption (range 77-127% of portal-drained viscera flux). Correlation coefficients between net hepatic and portal-drained viscera fluxes for leucine, valine, isoleucine, methionine and phenylalanine were 0.84 to 0.93. Postabsorptive hepatic extraction for most amino acids was zero, but after a meal, ranged from 13.3 to 22.9% for the branched chain and aromatic amino acids. Net hepatic production of ornithine and proline occurred in arginine-fed control rats. This value was near zero for ornithine in rats fed the arginine-deficient diet. Models of interorgan amino acid metabolism in the food-deprived and fed state are presented. PMID- 8360780 TI - Normal circulating triiodothyronine concentrations are maintained despite severe hypothyroidism in growing pigs fed rapeseed presscake meal. AB - Experiments were designed to study effects of dietary rapeseed presscake meal on the thyroid and on the liver 5'-monodeiodinase activity in growing pigs. Animals were fed rapeseed presscake meal (15% in the ration) of 0-varieties (containing relatively high amounts of glucosinolates and goitrin) or a control diet (soybean meal instead of rapeseed presscake meal) without or with thyroxine added to feed. Food intake and average daily gain were comparable because pigs were pair-fed. Serum thiocyanate concentration was significantly greater in pigs fed rapeseed presscake meal. Pigs fed rapeseed presscake meal developed hypothyroidism. Serum free thyroxine concentrations in rapeseed presscake meal-fed pigs were significantly lower than in controls, normal in thyroxine-supplemented pigs fed rapeseed presscake meal and significantly above normal in thyroxine-supplemented controls. Serum free triiodothyronine concentrations were not significantly influenced by rapeseed presscake meal feeding or thyroxine supplementation. Liver weight and total DNA content in pigs fed rapeseed presscake meal were higher than in controls but were not significantly affected by thyroxine feeding. Hepatic 5' monodeiodinase activity on a protein basis was lower in pigs fed rapeseed presscake meal and was not normalized by thyroxine supplementation. However, in whole liver, because of greater liver mass, 5'-monodeiodinase activity in pigs fed rapeseed presscake meal was similar to that in controls. The data indicate that serum free triiodothyronine concentrations in pigs fed rapeseed presscake meal could be maintained in the physiological range, probably because of enhanced triiodothyronine secretion and sufficient extrathyroidal thyroxine to triiodothyronine conversion. PMID- 8360781 TI - Lower food intake is a primary cause of reduced growth rate in growing pigs fed rapeseed presscake meal. AB - Rapeseed presscake meal (15% in the ration) of 0-varieties or a control diet (soybean meal instead of rapeseed presscake meal) was fed without or with thyroxine for 9-10 wk to growing pigs. Pigs fed rapeseed presscake meal developed hyperplastic goiter. Blood serum free thyroxine concentrations in rapeseed presscake meal-fed pigs were depressed, normal in thyroxine-supplemented pigs fed rapeseed presscake meal and above normal in thyroxine-supplemented controls, but serum free triiodothyronine concentrations were comparable in all groups. Feed intake and average daily gain were reduced in pigs fed rapeseed presscake meal, independent of oral thyroxine intake. However, in an additional experiment, in which food intake was comparable because pigs were pair-fed, average daily gain was similar. The data indicate that reduced growth performance of rapeseed presscake meal-fed pigs was primarily the consequence of decreased feed intake and that hypothyroidism was of lesser importance. PMID- 8360782 TI - Threshold for glucose-stimulated insulin secretion in pancreatic islets of genetically obese (ob/ob) mice is abnormally low. AB - Pancreatic islets were isolated from 8-9-wk-old female genetically obese (ob/ob) and lean mice to determine the glucose threshold for insulin secretion, and to examine effects of acetylcholine on insulin secretion. Only equal-sized islets from ob/ob and lean mice were incubated to eliminate confounding effects of phenotypic differences in islet size. Even after this adjustment, islets from ob/ob mice still hypersecreted insulin in response to 20 mmol/L glucose. The threshold for glucose-induced insulin secretion determined by perifusing islets with a linear glucose gradient averaged 1.9 +/- 0.1 mmol/L glucose in fed ob/ob mice and 3.1 +/- 0.1 mmol/L glucose in ob/ob mice after 24 h of food deprivation. These low thresholds indicate that islets from ob/ob mice are constantly stimulated by glucose. Islets from lean mice exhibited considerably higher thresholds (4.8 +/- 0.1 and 7.1 +/- 0.1 mmol/L glucose in fed and 24-h food deprived lean mice, respectively). Rates of insulin secretion per each unit (mmol/L) increase in glucose above threshold concentrations were unaffected by phenotype or feeding state. Addition of acetylcholine to the perifusing buffer further lowered the threshold for insulin secretion to 0.5 mmol/L glucose in pancreatic islets from ob/ob mice and also doubled the rate of increase in insulin secretion at glucose concentrations above the threshold. The combination of the very low threshold for glucose-induced insulin secretion and the exaggerated insulin secretory response to acetylcholine in pancreatic islets of ob/ob mice are likely critical factors in the hyperinsulinemia of these mice. PMID- 8360783 TI - A multi-element isotopic tracer assessment of true fractional absorption of minerals from formula with additives of calcium, phosphorus, zinc, copper and iron in young piglets. AB - True fractional absorption of minerals was measured to determine the bioavailability of Zn, Fe, Mn and Se from liquid formulas fortified with stepwise additions of Ca and P (as Ca glycerophosphate and carbonate, Ca*P), and Zn, Cu and Fe (as sulfate salts). Growth, deposition of tracers in organs and bone mineral content of femurs as assessed by single photon absorptiometry were measured. Four-day-old piglets (n = 36) were randomly assigned to groups fed a basal diet or additions of Ca*P (Ca = 25, P = 18 g/kg dry diet), Ca*P+Zn (Zn = 0.04 g/kg), Ca*P+Zn+Cu (Cu = 0.007 g/kg) or Ca*P+Zn+Cu+Fe (Fe = 0.008 g/kg). Oral and intravenous administration of extrinsic isotopes of 59Fe, 54Mn, 65Zn, 75Se and 47Ca was followed by fecal monitoring for 15 d and true absorption calculated after accounting for endogenous excretion. Addition of Ca*P+Zn reduced Zn absorption (P < 0.05) and Ca*P+Zn+Cu reduced Fe absorption (P < 0.01), but Mn and Se absorptions were not altered. Uptake of only Zn tracer into heart was significantly different (P < 0.05) among diet groups. Weight gain and linear growth were similar in all groups. Addition of Ca*P produced higher bone mineral density, but its effect on Zn absorption warrants further investigation. PMID- 8360784 TI - The dietary requirement of young rainbow trout (Oncorhynchus mykiss) for folic acid. AB - We sought to determine the dietary folic acid requirement of young rainbow trout using growth indices supported by measurements of tissue folate concentrations. The investigation was conducted with purified diets that had, by assay, basal folic acid levels of 0.08 and 0.16 mg/kg in the first and second, respectively, of two experiments. Each experiment was started with fry (initial mean weight, 1.4 and 2.8 g/fish in Experiments 1 and 2, respectively) and was conducted at a water temperature of 15 degrees C. Experiment 1 lasted 18 wk and Experiment 2 lasted 16 wk. Recovery tests (of 8 wk duration, performed on fish fed the unsupplemented diet) and pair-feeding showed that the unsupplemented diet led to a folate-specific deficiency condition in which the main hematological abnormality was the appearance of misshapen nuclei in a small proportion (2.3%) of erythrocytes. Dietary requirements were shown not to exceed 0.3 and 0.6 mg folic acid/kg (17 and 33 micrograms/MJ digestible energy) for optimizing survival and growth indices, respectively. We conclude that the dietary folate requirement of the trout is comparable to that of other vertebrates for the purpose of achieving maximal weight gain. PMID- 8360785 TI - Comments on the paper by Garwin et al. (1992) PMID- 8360786 TI - Comments on the paper by Garwin et al. (1992) PMID- 8360787 TI - Comment by A. H. Merrill, associate editor. PMID- 8360788 TI - Dietary factors influencing calcium and bone metabolism: introduction. PMID- 8360789 TI - Caffeine, urinary calcium, calcium metabolism and bone. AB - Oral doses of caffeine increase the urinary excretion of calcium, magnesium, sodium and chloride for at least 3 h after consumption. The hypercalciuric effect can be blocked by adenosine receptor agonists. The effect is proportional to dose per lean body mass and no adaptation to the urinary losses occurs with continuing consumption of caffeine. Uncompensated losses of calcium would be a risk factor for development of osteoporosis. Risks of osteoporosis due to caffeine consumption are reviewed. Comparison of data from epidemiological surveys and animal and human studies suggests that for younger adult women consuming adequate calcium, moderate caffeine intakes may have little or no deleterious effects. Increased urinary and intestinal losses may be compensated for by increased intestinal calcium absorption. However older women do not seem to compensate adequately to maintain their former calcium balance, especially when calcium intakes are below recommendations. PMID- 8360790 TI - The nature and significance of the relationship between urinary sodium and urinary calcium in women. AB - Orally or parenterally administered sodium is known to increase urinary calcium in experimental animals and humans, and there is well-documented correlation between urinary sodium and calcium in 24-h urine collections from normal subjects and renal stone formers. The correlation between urinary sodium and calcium is generally sodium driven, i.e., it is the sodium load that influences urinary calcium rather than vice versa, but the converse may also occur, as after an oral calcium load or in hypercalcemia. When sodium is the determinant, 100 mmol of sodium takes out approximately 1 mmol of calcium in the urine. When calcium load is the determinant, each millimole of calcium appearing in the urine is associated with an extra 10-20 mmol of sodium. Sodium-dependent calcium loss may continue indefinitely, but calcium-dependent natriuresis is self-limiting. There is a significant correlation between calcium and sodium in fasting urine from both pre- and postmenopausal women, but there is more calcium relative to sodium in postmenopausal women than in premenopausal women. In postmenopausal but not premenopausal women, urinary hydroxyproline is also related to obligatory sodium and calcium output, and restriction of salt intake lowers not only urinary sodium but also calcium and hydroxyproline. There is not only an increase in obligatory calcium excretion at the menopause, but also an increase in the fasting urinary sodium, which in turn accounts for some of the increase in calcium output. This rise in fasting urinary sodium represents a delay in sodium excretion that may have a significant effect on calcium homeostasis. PMID- 8360791 TI - Potassium causes calcium retention in healthy adults. AB - The administration of 60 mmol/d of KHCO3 to healthy adults reduced urinary calcium excretion by 0.9 mmol/d and caused calcium balance to become equivalently more positive. Other studies showed that 90 mmol/d of KHCO3 reduced both daily and fasting urinary calcium excretion rates, whereas deprivation of either KCl or KHCO3, using synthetic diets, was accompanied by increased daily and fasting urinary calcium excretion rates. A significant inverse relationship between the changes in urinary calcium and the changes in urinary potassium was observed: delta urinary Ca (mmol/d) = 0.29-0.015 delta urinary K (mmol/d); r = -0.65. Correlative evaluation of additional data suggested that the fall in urinary calcium during potassium administration may be related to the natriuretic effects of potassium, resulting in ECF-volume contraction or to potassium-induced phosphate retention and suppression of calcitriol synthesis, or to both mechanisms. PMID- 8360792 TI - Dietary phosphorus, calcium metabolism and bone. AB - Many American women consume diets high in phosphorus and low in calcium. Concern about this dietary pattern stems from studies that show high phosphorus, low calcium intake causes secondary hyperparathyroidism and bone loss in several animal models. Recent studies in young adults have shown that a high phosphorus, moderately low calcium intake results in mild secondary hyperparathyroidism that persisted over 4 wk. However, plasma concentrations of the active form of vitamin D did not change in these subjects, despite stimulatory changes in parathyroid hormone and serum ionized calcium. Studies in normal adult men have shown that dietary phosphorus at levels within the observed normal range of intake can finely regulate the renal production and serum concentration of 1,25 dihydroxycholecalciferol. Thus, prolonged high phosphorus intake may impair the usual homeostatic mechanisms that are evoked when dietary calcium is limited. The current dietary patterns of high phosphorus, low calcium consumption result in persistent changes in the calcium regulating hormones that are not conductive to optimizing peak bone mass or slowing the rate of bone loss. PMID- 8360793 TI - California grapples with hygiene demands for independent provider status/diagnosis. PMID- 8360794 TI - Antibodies to Sm, RNP and SSB detected by solid-phase ELISAs using recombinant antigens: a comparison study with counter immunoelectrophoresis and immunoblotting. AB - Sera from 64 patients with systemic lupus erythematosus (SLE) were tested for the presence of anti-Sm, anti-RNP, and anti-SSB antibodies using commercially available solid-phase enzyme-linked immunosorbent assays (ELISAs) and recombinant nuclear proteins as substrates. The results were compared to those obtained with counterimmunoelectrophoresis (CIE) and immunoblotting (IBT) using a rabbit thymus extract (RTE) as the substrate. The ELISAs detected antibodies to Sm, RNP, and SSB in, respectively, 25%, 36%, and 15% of the SLE sera. Neither IBT positive/ELISA-negative nor CIE-positive/ELISA-negative sera were found, regardless of the specificity considered, suggesting that ELISAs using recombinant nuclear antigens are highly sensitive. Discrepancies were observed between the results obtained with these different techniques. In addition to sera positive by both IBT and ELISA but negative by CIE, a substantial number of sera had ELISA-detectable anti-Sm, anti-RNP, and anti-SSB antibodies which failed to react with the corresponding polypeptides by IBT. The reasons for ELISA/IBT discrepancies were explored; however, no single explanation was found. Instead, a higher sensitivity of the ELISA to detect antibodies directed against certain polypeptides, the possible inability of IBT using RTE as the substrate to detect antibodies reacting with conformational antigenic determinants, and false positive reactions in the ELISAs were suggested. Thus, it is still advisable to perform both IBT and ELISAs simultaneously in well-defined autoimmune diseases to further analyze the potential advantages of ELISAs using recombinant antigens. PMID- 8360795 TI - Application of checkerboard immunoblotting (CBIB) to the detection of anti-viral IgG in human serum. AB - In the present study, we have begun to investigate the possibility of using checkerboard immunoblotting (CBIB) as a semi-quantitative screening tool for detecting human serum IgG against specific viral antigens. The viral antigens studied were Epstein-Barr, herpes simplex I and II, cytomegalovirus, varicella zoster, rubella, rubeola, and mumps. Western immunoblotting experiments using these partially purified preparations demonstrated that there were apparently no interactions between IgG from non-immune sera and the respective viral antigen preparations. The CBIB assay was evaluated using sera of known positive or negative immune status for the viral antigens. There was excellent agreement between the results of CBIB and the results of alternative methods for evaluating immune status: all discrepancies (1/18 sera for mumps, 3/18 sera for rubeola, and 1/28 sera for rubella) involved sera with borderline results, either by CBIB or by the alternative method. Therefore, although further work is required to define the method in terms of sensitivity and clinical specificity, and to refine positive/negative cutpoint criteria for certain antigen components, our preliminary experience suggests that CBIB has considerable potential in the efficient and inexpensive screening of sera for the presence of IgG against a panel of viral antigens, so as to identify subjects at risk for infection. PMID- 8360796 TI - Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy. AB - The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). H2O2 production by PMN after stimulation was measured using flow cytometry. Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function. H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls. This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation. Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function. It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy. PMID- 8360797 TI - Specificity of an immunochemical reagent for quantifying the isoforms of creatine kinase-MB. AB - Fractionation of the creatine kinase-MB isoforms is promising for use in diagnosing acute myocardial infarction and for monitoring myocardial perfusion status after thrombolytic therapy. An immunochemical reagent intended for use in fractionating the MB1 and MB2 isoforms of creatine kinase-MB was examined before and after immunoextraction, qualitatively by visually examining electrophoresis separation of various MB1 and MB2 mixtures, and quantitatively by comparing the observed and predicted enzymatic activity of various MB1 and MB2 mixtures. Qualitatively the reagent showed greater reactivity for MB1 than for MB2, as demonstrated by a marked decrease in the MB1 electrophoretic region following immunoextraction. Quantitatively, the reagent consistently eliminated about 75% of MB1 activity; however, the assay also eliminated about 40% of MB2 activity from isoform mixtures. Although the performance of the immunochemical reagent was not ideal, the greater reactivity for MB1 may have clinical use. PMID- 8360798 TI - Improved measurement of anti-thyroglobulin IgG in urine of patients with autoimmune thyroid diseases by sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay. AB - Previously, antithyroglobulin IgG was assayed in dialyzed urine from patients with autoimmune thyroid diseases by a sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay), and most of the assay results were useful as a diagnostic aid for autoimmune thyroid diseases. However, dialysis of urine was laborious and time-consuming, and some results were less reliable due to low levels of anti-thyroglobulin IgG in urine. This paper describes some improvements of the assay. Useful assay results could be obtained for most of urine samples without dialysis, although some interfering substance(s) was suggested to be present in some urine samples before dialysis. Accurate assay results with no interference could be obtained after gel filtration by only two min centrifugation in place of dialysis. More reliable assay results for urine samples containing low levels of antithyroglobulin IgG were obtained after concentration using a molecular sieve. PMID- 8360799 TI - Immunocytodiagnosis of solid tumors employing panels of monoclonal antibodies. PMID- 8360800 TI - Correlation between human sperm hypo-osmotic swelling test and other semen parameters. AB - Ninety semen samples from male patients were studied. They were classified into 4 different groups; normospermic fertile, oligospermia, asthenospermia, and oligoasthenospermia. In addition to routine semen analysis, the hypo-osmotic swelling test was done for all these samples, measuring total protein and specific gravity. A significant positive correlation was observed between percent sperm swelling and its motility, its total protein, and specific gravity. Also a significant negative correlation was noticed between percent sperm swelling and its count. Although there were overlapping ranges, different groups showed significant relations of percent sperm swelling among themselves. It is postulated that the sperm quality and not its quantity is the cornerstone of the hypo-osmotic test and that the physico-chemical properties of the sperm influences its swelling. PMID- 8360801 TI - Meeting of the Parenteral Society. PMID- 8360802 TI - ISO 9000. Policy implications for FDA. Taking the pulse of increasing global use of the ISO series of uniform quality standards by FDA regulated industries. PMID- 8360803 TI - Thermal mechanical analysis of frozen solutions of mannitol and some related stereoisomers: evidence of expansion during warming and correlation with vial breakage during lyophilization. AB - The mechanical properties of frozen mannitol, L-iditol, dulcitol, and sorbitol solutions were measured as a function of temperature during warming (after freezing) using a thermal mechanical analyzer (TMA). The mannitol sample first underwent a contractive phase starting at 30 degrees C and ending at -25 degrees C. This was followed by an initially rapid, then less rapid expansive phase which continued until melting occurred. These events provide direct evidence that mannitol solutions undergo an expansion during warming after "fast" freezing and also corroborate the vial breakage observed when mannitol solutions are frozen and thawed or freeze-dried in glass vials. Of the other stereoisomers studied, only dulcitol had an expansive phase although at a slower rate than mannitol. Its solution was found to cause vial breakage also but only at fill volumes higher than mannitol fill volumes. TMA is a useful technique for studying dimensional changes in the frozen state, with important implications for solving vial breakage problems in freeze-drying. PMID- 8360804 TI - IV fluidmakers: preparation of sterile water for injection in a field setting. AB - Two approaches have been investigated for generating USP sterile, pyrogen-free water for injection (WFI) from potable water in the field. The first approach utilizes reverse osmosis (RO), ion exchange, a solid matrix filter containing activated carbon and zeta adsorbent, a final 0.2 microns pore size sterilizing filter and a device for transferring the WFI to an IV bag; prototype systems based on three different hand-operated RO units weigh 1.5-3.5 kg and are capable of producing WFI at rates of 1-10 L/hr. Parenteral solutions were made by adding WFI to an IV bag containing concentrated Ringer's lactate. The second approach, still in the breadboard stage, is similar but utilizes a larger ion exchange column in place of the RO unit and a multiport distribution head to fill a set of 18 1-L IV bags. This system, considered to be disposable, is capable of generating water of WFI quality at a fill rate of 0.5 L/min from a pressurized source. PMID- 8360805 TI - Particle size reduction of emulsions by formulation design. I: Effect of polyhydroxy alcohols. AB - The objective of this study was to characterize the effect on particle size and stability of oil-in-water emulsion formulations caused by the addition of polyhydroxy alcohols. Stable soybean oil and hexadecane emulsions were prepared containing increasing amounts of propylene glycol (PG) and glycerol (GLY). A nonionic emulsifier system consisting of Tween 80 and Span 80 was used to achieve optimal stability. Particle size was found to decrease as the level of PG or GLY increased. A three-fold particle size reduction was obtained at a PG level of 40% w/w and at a GLY level of 70% w/w. The particle size of soybean oil emulsions decreased from about 4.8 microns to about 1.7 microns. The particle size of hexadecane emulsions decreased from about 2.7 microns to less than 1 micron. The increase in emulsion viscosity was found to be proportional to the amount of polyhydroxy alcohols added to the formulation. The particle size and creaming stability of the emulsions were found to improve with increasing PG or GLY concentration. PMID- 8360806 TI - Stability of cefazolin sodium and metronidazole at 8 degrees C for use as an i.v. admixture. AB - The stability of cefazolin 1 g in metronidazole 500 mg/100 mL at 8 degrees C was studied for use as an IV admixture. The commercially available injection of cefazolin sodium 1 g vial was diluted to 5 mL with 0.9% sodium chloride injection and added to metronidazole 500 mg/100 mL. Following dilution of 2 mL to 100 mL with water, 1-mL aliquots were transferred to glass vials, refrigerated at 8 degrees, and assayed for cefazolin and metronidazole concentration at 0, 1, 2, 4, 8, 12, 24, 36, 48, and 72 hours after preparation. The concentration of cefazolin and metronidazole was determined by a stability-indicating high-performance liquid chromatographic method. The range of concentration was determined to be within 5% of the 0-hour mean concentration. Over the 72-hour period, the mean concentration of cefazolin at all assay times was within 98.4 to 101.0% of the initial concentration. The mean concentration of metronidazole at each assay time was 96.9 to 104.9% of the initial concentration. Cefazolin sodium 10 mg/mL and metronidazole 5 mg/mL, prepared by adding reconstituted cefazolin to a glass bottle of metronidazole ready-to-use solution, were stable for 72 hours when stored at 8 degrees C. PMID- 8360807 TI - Comparative terminal sterilization. AB - Thermal processing of product in its final container to achieve product safety has been a major process operation of the pharmaceutical and food industries for many years. The original batch type autoclave (retort) is still in prevalent use today. However, high volume continuous and semi-continuous methods are also utilized, primarily in the food industry. Each different terminal sterilization method and load type requires assurance of process adequacy. This paper examines some of the types of moist heat terminal sterilizers in both the pharmaceutical and food industries and compares their features. PMID- 8360808 TI - The validation life cycle. AB - The Validation Life Cycle is an implementation mechanism which can assist pharmaceutical (and other types of medical product) manufacturers in the organization and execution of validation activities. A considerable body of work exists which identifies how to validate processes of various type and description. Unfortunately, there is a paucity of information on how to organize these individual validation activities into a cohesive whole. This paper describes a suggested means for achieving an organization's validation goals in a rational and effective fashion. To best understand the advantages of a life cycle for validation, a recap of the history of validation in the U.S. pharmaceutical industry is useful. PMID- 8360809 TI - Histoplasma capsulatum and V beta a mice: cellular immune responses and susceptibility patterns. AB - Certain strains of mice, designated V beta a, have a deletion of the gene segments encoding the beta chain of the T-cell receptor variable region. These mice do not express 40 to 50% of the T-cell receptor V beta chains. In this study, we examined the influence of this deletion on susceptibility to Histoplasma capsulatum. In addition, H. capsulatum-injected V beta a mice were tested for their capacity to generate T-cell dependent responses to H. capsulatum antigens. Susceptibility profiles of V beta a mice, SWR/J (H-2q), SJL/J (H-2s) and C57L-(H-2b), were compared to V beta b strains, C57BL/6 (H-2b) and DBA/l (H 2q), following intravenous (IV) injection of sublethal and lethal inocula of H. capsulatum yeast cells. One week after injection of 6 x 10(5) yeast cells, the spleens of SWR/J, SJL/J and C57L mice contained 5- to 7-fold fewer colony forming units (CFU) than spleens of C57BL/6 mice. Approximately 50% fewer CFU of H. capsulatum were recovered from the spleens of DBA/l mice compared to those from C57BL/6 animals. Subsequently, groups of mice were challenged IV with either 1.5 x 10(7) or 7.5 x 10(6) yeast cells and observed for 30 days. Survival of SWR/J,SJL/J, C57L and DBA/l mice was significantly prolonged compared to C57BL/6 mice. V beta a and DBA/l mice injected with viable H. capsulatum yeast cells mounted a delayed-type hypersensitivity response to an extract from the cell wall and cell membrane of yeast cells and to HIS-62, a purified antigen derived therefrom.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360811 TI - An improved culture medium for detecting live yeast phase cells of Paracoccidioides brasiliensis. AB - The plating efficiency of standard mycological media such as brain heart infusion (BHI) agar is poor for Paracoccidioides brasiliensis. We prepared a water-extract of yeast phase cells of P. brasiliensis and examined it for growth-enhancing activity for the fungus. The water-extract, when added to BHI agar to a concentration of 5%, improved the plating efficiency of the medium for the fungus to some extent, but the degree of improvement was considerably varied among P. brasiliensis isolates. By contrast, when the water-extract was added in combination with horse serum (4%), the plating efficiency was highly improved (to 94-99%) for all the P. brasiliensis isolates employed. The growth-enhancing factor(s) in the water-extract was heat-stable and heating at 120 degrees C for 15 min had little, if any, effect on growth-enhancing activity. PMID- 8360810 TI - Differential binding of acapsulate and encapsulated strains of Cryptococcus neoformans to human neutrophils. AB - Investigations into mechanisms of binding of encapsulated and acapsulate strains of Cryptococcus neoformans by human neutrophils were performed, using a monolayer assay. The two strains bound to neutrophils by different mechanisms although both had an absolute requirement for opsonization with complement components in normal human serum for binding to occur. Neutrophil binding of encapsulated yeasts required conformational changes in actin yet did not appear to lead to phagocytosis of the organism. A maximum of 12 acapsulate cells bound per neutrophil compared with only four encapsulated yeasts. Cytochalasin D treatment reduced the maximum numbers able to bind per neutrophil by 50%. The encapsulated cryptococci appeared to compete with each other for binding to neutrophils whereas the acapsulate yeast cells bound to neutrophils in an approximately Poisson distribution, suggesting independent binding. Binding of acapsulate cryptococci did not require actin filaments and appeared to trigger phagocytosis. Thus, the capsule of C. neoformans appeared to inhibit binding and internalization by neutrophils. PMID- 8360812 TI - Efficacy evaluation of a novel submicron amphotericin B emulsion in murine candidiasis. AB - A submicron amphotericin B (AmB) sterile emulsion with a mean droplet size of approximately 100 nm was prepared. The emulsion was stable at 4 degrees C over a period of 4 months. The acute toxicity results showed that the maximum tolerated dose of the AmB emulsion was 2.0 mg kg-1 as compared to 0.5 mg kg-1 for a commercial deoxycholate suspension, Fungizone. Efficacy evaluations of submicron AmB emulsion compared to Fungizone were performed in a murine candidiasis model using either a single or a multiple daily dose administration of 0.4 mg kg-1. Survival (100%) was observed up to 15-18 days post-infection in mice treated with AmB emulsion or Fungizone, while all control non-treated animals had died after 9 days in both single and multi-treatment experiments. Survival (50%) was obtained after 35 days in the single treatment, and 40 days in the multi-treatment, experiment with AmB emulsion, while treatment with Fungizone gave 50% survival after 15 and 20 days, respectively. The overall results indicate that in murine candidiasis, treatment with AmB submicron emulsion was more effective than Fungizone, suggesting a potential therapeutic application. PMID- 8360813 TI - Qualitative and quantitative differences in recognition patterns of Candida albicans protein and polysaccharide antigens by human sera. AB - Cytoplasmic and cell wall proteins and glycoproteins extracted from Candida albicans germ tubes were screened by Western blotting for their ability to differentiate between the serological responses of patients with candidosis and healthy individuals. Molecules of 114, 74 and 65 kDa were not recognized by any sera. Qualitative differences were observed for responses to proteins and glycoproteins from 29 to 60 kDa. Conversely, only quantitative differences were found to high molecular mass glycoproteins. Their recognition by control sera was invariably associated with reactivity against a 14-18 kDa antigen. However, despite a high level of antibodies against high molecular mass mannoproteins, some patients sera failed to react with the 14-18 kDa antigen, or lost this reactivity during the course of the disease. PMID- 8360814 TI - Identification of Candida albicans cell wall antigens lost during subculture in synthetic media. AB - A high variability in reactivity was observed when Candida albicans strains freshly isolated from both patients with candidiasis and asymptomatic carriers were tested against different human sera. The highest reactivity was observed in C. albicans strains isolated from blood cultures. This high reactivity was observed when the isolates were tested against sera from patients with Candida oesophagitis, patients with vulvovaginal candidiasis, or asymptomatic carriers but not against sera from blood donors. The antigenic reactivity of the strongly reactive strains, but not that of the weakly reactive strains, decreased during subculture in synthetic media. Five major components of an apparent molecular mass of > 200, 67-70, 49-52, 33-35 and 29-31 kDa were observed in alpha mannosidase extracts from C. albicans strains from both blood cultures (Group I) and patients with Candida oesophagitis (Group II) subcultured in synthetic media for different times. Changes in staining intensity through the different subcultures were observed for some bands. Group I strains showed a decrease in staining intensity for bands of > 200 and 67-70 kDa, an increase for bands of 33 35 and 29-31 kDa, but no changes were observed for the band of 49-52 kDa. Group II strains showed opposite changes in banding intensity. A decrease in staining intensity was observed for the proteins of 33-35 and 29-31 kDa, an increase for the protein of 49-52 kDa, and no change in intensity was observed for the band of 67-70 kDa. A component of > 200 kDa showed an irregular expression through the subcultures. The main antigen present in extracts from the first subculture of isolates from Group I and II had a molecular mass of 67-70 kDa. It could be related to the P antigens since it disappeared following subculture of the strains in synthetic media. PMID- 8360815 TI - Sch 39304, a new antifungal agent: oral and topical treatment of vaginal and superficial infections. AB - Sch 39304 is a new broad spectrum triazole antifungal agent that is active, orally and topically, against superficial Trichophyton mentagrophytes and vaginal Candida albicans infections. Sch 39304 was compared to fluconazole (FLZ) in a T. mentagrophytes infection model in guinea pigs. Following topical administration, Sch 39304 (0.125%, twice daily, 10 days), was 5-8-fold more effective than FLZ, based on culture and lesion score results. Following oral administration, Sch 39304 (2.5 mg kg-1, once daily, 10 days) produced a dramatic reduction in lesion scores and was 20-fold more active than FLZ; however, due to the length of time it takes for the drugs to reach the infected area of the skin and eradicate the infections, most animals remained culture positive with both drugs. Sch 39304 was also compared with FLZ in a vaginal C. albicans infection in hamsters. Following oral administration (4 days), Sch 39304 (1.6 mg kg-1), cured all hamsters and was 4-fold more active than FLZ. In addition, Sch 39304 as a single oral dose (10 mg kg-1) also cured all hamsters. When treatment was intravaginal (8 days), Sch 39304 was again more active than FLZ (2-fold), and also micronazole (8-fold), with 100% of the hamsters cured at concentrations as low at 0.025%. PMID- 8360816 TI - Placental involvement in paracoccidioidomycosis. AB - A case of juvenile-type paracoccidioidomycosis in a pregnant woman is reported. The disease pre-dated pregnancy and antifungal treatment was being administered when she became pregnant. A premature male infant was delivered with no evidence of infection. Microscopic examination of the placenta showed numerous Paracoccidioides brasiliensis yeast forms in the intervillous space, enmeshed in a macrophagic-phagocytic reaction, with damage of the trophoblastic layer. Placental transfer of specific P. brasiliensis antibodies was demonstrated. PMID- 8360817 TI - Fluconazole in patients at risk from invasive aspergillosis. AB - We report on four cases of aspergillosis which developed during therapy with fluconazole in patients who were immunosuppressed or granulocytopenic. Fluconazole may obscure the onset of aspergillosis. We feel that it should neither be given prophylactically nor for fever of unknown origin in patients who are at high risk of contracting aspergillosis. PMID- 8360819 TI - Pharmaceutics and drug delivery aspects of heme and porphyrin therapy. AB - The importance of porphyrins and metalloporphyrins as therapeutic drugs has increased significantly over the last decade. This review highlights some of the challenges faced by pharmaceutical scientists in formulating these drugs into stable, effective, and safe dosage forms. Most activity in the clinic has focused on three areas: photodynamic therapy of cancer (e.g., hematoporphyrin derivatives), porphyrias and hematological diseases (e.g., heme), and various forms of jaundice (e.g., tin porphyrins). The biodistribution, stability, aggregation, toxicology, and analytical methodology of porphyrin drugs are all important considerations in the pharmaceutical development of porphyrin drugs. The utility of delivery systems such as liposomes hold promise of increasing the therapeutic potential of these drugs. Future prospects for therapeutic applications of porphyrin drugs are also discussed. PMID- 8360818 TI - Transdermal iontophoretic peptide delivery: in vitro and in vivo studies with luteinizing hormone releasing hormone. AB - Protein and peptide drugs are not orally active. Their large molecular size and charged character make them poor candidates for passive transdermal delivery. With an applied electromotive force, these drugs can be forced through the skin to be absorbed by the systemic circulation. The present study investigates the transdermal iontophoretic delivery of a peptide hormone in an in vitro model system, the isolated perfused porcine skin flap, as well as in vivo. It is shown that with knowledge of the systemic disposition of the drug, transdermal fluxes can be utilized to accurately predict in vivo serum concentrations. It is also shown that the iontophoretically delivered hormone retains both its immunologic and biologic activity. PMID- 8360820 TI - Percutaneous absorption: a single-layer model. AB - In vitro percutaneous permeation of betamethasone 17-valerate through excised human skin was studied. Pressure-sensitive silicone adhesive containing betamethasone 17-valerate in suspension was used as a vehicle. Steady-state flux through the split-thickness skin was similar to that through the isolated epidermis. However, the lag-time and half-life after removal of the vehicle were longer for the split-thickness skin than from epidermis. At steady state, 37% of the drug in the split-thickness skin was partitioned in dermis. When the kinetic parameters of a simple single-layer model are defined to specify the permeability coefficient and the drug amount in skin at steady state, this model can predict the longer half-life observed for the split-thickness skin sample compared with that for epidermis. The difference between the observed and theoretical values of the half-life after removal of the vehicle was within 23%. On the other hand, the lag-time had a large variation and the simple diffusion model failed to be predictive. A single-layer model described by two or three kinetic parameters may be able to describe percutaneous permeation kinetics even when the processes after the compound permeation through stratum corneum are not negligible. However, it is stressed that none of the kinetic parameters inherent in this simple model directly represents one of the single physicochemical parameters, such as diffusion and partition coefficients and path length of each skin layer. PMID- 8360822 TI - Effects of protein binding on the isomerization of ceftibuten. AB - Isomerization of ceftibuten to trans-ceftibuten, a less active isomer of ceftibuten, was observed in human serum in vitro. Investigation of the isomerization mechanism in the serum clarified that albumin accelerated the isomerization. The isomerization rate constant correlated significantly with the percent of binding to albumin, suggesting the binding of ceftibuten to albumin might be the driving force for the isomerization under in vitro conditions. This isomerization was also observed in clinical studies in humans. Results of physiological model analysis indicate that the isomerization catalyzed by albumin contributes significantly to the overall isomerization in the human body following oral administration. PMID- 8360821 TI - Reaction-frequencymetric method: a new analytical technique for determination of submicromolar concentration levels of vitamin C. AB - A new analytical technique for the assay of pharmaceutical substances at low concentration levels has been proposed and applied to the determination of vitamin C as an example of its application. It is based on the chemical reaction of vitamin C with iodine in a sodium citrate-hydrochloric acid medium, followed by measurement of the frequency change of a silver-plated piezoelectric quartz crystal. The frequency change is proportional to the vitamin C concentration from 2 x 10(-7) to 4 x 10(-6) M. The method was applied to the assay of vitamin C in pharmaceutical preparations. PMID- 8360823 TI - Molecular organization of liquid n-octanol: an X-ray diffraction analysis. AB - We recorded X-ray diffraction patterns from n-octane, n-octanol, and fully hydrated n-octanol. These patterns were analyzed using a modified version of the Percus-Yevick hard-sphere theory for liquids. A model is presented for the molecular organization of n-octanol that accurately predicts the observed diffraction patterns. The octanol molecules are associated in aggregates, with their hydroxyl groups forming roughly spherical clusters and their hydrocarbon chains pointing outwards, almost fully extended. When n-octanol is hydrated, the overall organization does not change greatly, but water molecules coordinate the hydroxyl groups in the clusters. Estimates are made for the maximum number of octanol molecules in the aggregates. PMID- 8360824 TI - A specific radioimmunoassay for the measurement of gadoteridol, a contrast agent for magnetic resonance imaging in biological fluids. AB - Gadoteridol, a nonionic gadolinium chelate, is currently being evaluated for contrast-enhanced magnetic resonance imaging. A radioimmunoassay (RIA) has been developed for the measurement of gadoteridol in biological fluids. The RIA has a range of 0 to 25 micrograms/mL and has the sensitivity to detect 0.05 microgram/mL of gadoteridol. Satisfactory zero binding and sensitivity were obtained after an overnight incubation at 4 degrees C. Separation of the antibody bound and free radiolabel was achieved with 12.5% polyethylene glycol. A quantitative recovery of the exogenous analyte was obtained at all concentrations of gadoteridol tested. Linearity in both serum and urine was satisfactory. Intraassay coefficients of variation were 6.4 and 2.8% for the low and medium controls, respectively. Interassay coefficients of variation were 5.4, 3.8, and 12.2% for the low, medium, and high controls, respectively. Cross reactivities of the ligand 5 and the calcium salt 6 were 37 and 29%, respectively. Clinical samples from the ascending dosage studies were analyzed by the gadoteridol RIA. The results obtained from the serum specimens demonstrated an excellent linear proportionality between drug concentration in blood and administered dosage of gadoteridol. Cumulative urinary excretion data showed that 94% of the drug was excreted in the urine within 24 h. PMID- 8360825 TI - Displacement of thiopental from human serum albumin by associated drugs. AB - Displacement of thiopental from its binding sites to 4% human serum albumin solution was studied in vitro. Experimental conditions were selected to reproduce a physiological situation. Associations were studied according to the therapeutic conditions of use of the substances (drug and protein concentrations). The unbound fraction of thiopental was obtained by equilibrium dialysis at 37 degrees C and pH 7.4. Eleven drugs were associated with thiopental in 50 combinations of drugs and molar ratios. Bromhexine, citocoline, dextromoramide, dexamethasone, and methotrimeprazine had no effect on thiopental binding. The unbound fraction of thiopental significantly increased with cefamandole, cefazolin, diazepam, desmethyldiazepam, furosemide, and fentanyl. At usual therapeutic drug concentrations, the unbound fraction increase was < 5%. Higher values, however still < 10%, were found with associated drugs that were added at maximal concentrations observed in therapy. The displacement of thiopental from its albumin binding by drugs that are normally associated with the treatment of intracranial hypertension does not modify the pharmacokinetic parameters or pharmacological effect of thiopental. PMID- 8360826 TI - Formation and characterization of cyclosporine-loaded nanoparticles. AB - The commercially available formulations of cyclosporine (cyclosporin A, CyA) are associated with acute hemodynamic changes that result in high nephrotoxicity. Among colloidal vectors, nanoparticles (NPs) are receiving much attention as potential drug carriers that would avoid the therapeutic risks of conventional formulations. Two different mechanisms for obtaining polymeric NPs loaded with CyA were studied with regard to their preparation and physicochemical characterization. Isobutyl-2-cyanoacrylate monomer (IBCA) was polymerized, whereas poly-E-caprolactone (PCL, a preformed polymer) was precipitated; both reactions took place in an aqueous medium containing Pluronic F-68 (polyoxypropylene polyoxyethylene block copolymer) as a surface active agent. The encapsulation efficiencies were 78.49 +/- 5.87 and 84.85 +/- 5.02%, respectively, and they remained stable over a wide range of drug concentrations. The polymeric NP had average sizes of 81 +/- 25 and 95 +/- 25 nm for poly-IBCA and PCL, respectively, as confirmed by photon correlation spectroscopy. Poly-IBCA NPs were built from oligomers with molecular weights of 157 to 2644 that joined to form a polymeric nanomatrix. In vitro activity of the drug and the carrier was tested by inhibition of lymphocyte proliferation induced by Concanavalin A. Drug-loaded PCL NPs and free CyA inhibited lymphocyte proliferation by 91.40 and 86.19%, respectively. However, drug-free NPs also exhibited statistically significant (p < 0.05) immunosuppressive activity. PMID- 8360827 TI - Ion-pair reversed-phase liquid chromatographic identification and quantitation of papaverine congeners. AB - A reversed-phase ion-pair high-performance liquid chromatographic separation was developed for identification and quantitation of papaverine drug congeners, namely papaverine (1), moxaverine (2), drotaverine (3), and ethaverine (4) hydrochlorides. A synthetic reference mixture of the four congeners in the range 1-4 micrograms showed good separation. With a reference standard (codeine phosphate), the relative retention times to codeine were 1.356, 1.984, 2.46, and 2.91 (mean of six) for 1, 2, 3, and 4, respectively. Good linearity was obtained in the quantitation of 1 and 2 in the range 1-2 micrograms [correlation coefficient (r), 0.9978 and 0.9997, respectively] and 3 and 4 in the range 2-4 micrograms, (r, 0.9998 and 0.9991, respectively). Analysis of some commercial dosage forms containing one of these congeners showed good recovery with sufficient accuracy and precision. The method was sensitive and permitted the use of small sample sizes or unit doses. PMID- 8360828 TI - Toxin-targeted design for anticancer therapy. I: Synthesis and biological evaluation of new thioimidate heterobifunctional reagents. AB - In an effort to obtain a more potent and specific immunotoxin for cancer therapy, we designed a series of heterobifunctional linkers characterized by a thioimidate group linked to a S-acetyl thiol (4, 5) or substituted aryldithio group (6-10). These ligands were synthesized by a Pinner-type process from the corresponding nitrile derivatives obtained by thiol-disulphide exchange reaction, reaction with substituted benzene-sulphenyl chloride, or other known procedures. To check the reagent of choice for immunoconjugate preparation, we studied thioldisulphide exchange kinetics between the intermediate nitrile derivatives and cysteine. Among the tested aryldithio derivatives (6-10), we selected ethyl 3-(4 carboxamido-phenyldithio)propionthioimidate (CDPT, 9) for further studies. By analyzing the rate of incorporation of the linkers 4, 5, and 9 in a model immunoglobulin G protein, we found similar results with CDPT 9 and ethyl S-acetyl 3-mercaptopropionthioimidate ester hydrochloride (AMPT, 5) because both reagents showed a linear correlation between the number of introduced thiol groups and factors such as time and protein and reagent concentrations. Comparison of the two acetylthio-derivative ligands 4 and 5 showed that AMPT 5 was more stable toward deacetylation than ethyl S-acetyl 2-mercaptopropionthioimidate ester hydrochloride (AMAT, 4). By comparing the kinetic and biological parameters of seven new thioimidate linkers, we found that two of these (CDPT and AMPT) could be superior ligands for protein-protein conjugation. They offer advantages over the commercially available compounds, such as minimal perturbation of the protein structure, controlled reactivity, and good stability. PMID- 8360830 TI - Extraction and analysis by high-performance liquid chromatography of antibiotics in a drug delivery system for farmed fish. AB - Simple assays for extraction and determination of the concentrations of the antibiotics oxytetracycline, oxolinic acid, and flumequine in a drug dosage form for farmed fish are described. HPLC with UV detection was used in the analyses. The recovery of all three drugs was approximately 100%, and the precision varied from 0.5-3.0%. The methods are applicable to the production control, quality control, and stability control of the products. PMID- 8360829 TI - Antiserotoninergic activity of 2-aminoethylbenzocyclanones in rat aorta: structure-activity relationships. AB - The antiserotoninergic activity at the serotonin receptor subtype 2 (5-HT2) of seven new 2-aminoethylbenzocyclanones was determined with respect to serotonin induced contractions in rat aorta and compared with that of ketanserine (pA2 = 8.87). Competitive antagonism was observed in six compounds (6.72 < or = pA2 < or = 8.12). Three-dimensional structures and molecular electrostatic potential distributions of ketanserine and 2-aminoethylbenzocyclanones were analyzed. Several molecular features correlated with the rank of antiserotoninergic activity. In the case of the cyclanone fragment, the rank of activity was associated with the degree of planarity of the bicyclic system. The steric and electrostatic effects due to the loss of planarity were analyzed. In the case of the amino moiety, activity was associated with a particular spatial pattern defined by the amino nitrogen, the aromatic system, and molecular electrostatic potential minima generated by the oxygen atom. PMID- 8360831 TI - Quantitative structure-activity relationships for substituted aminotetralin analogues. II: Inhibition of dopamine uptake. AB - Quantitative structure-activity relationships of 44 substituted aminotetralin analogues with regard to dopamine (DA) uptake inhibitory potency are examined in this study. Lipophilic substituents at R3 and hydrophilic substituents at R6 and/or R9 positions, as well as the overall lipophilicity of the molecule contribute toward increasing the inhibitory potency. Unlike with norepinephrine uptake inhibition, little effects are seen from the nitrogen substituent. Among the ring substituents examined, an hydroxy group at the R6 position increases the DA uptake inhibitory potency, whereas a methoxy group at the R7 position decreases it. A comparative quantitative structure-activity relationship study shows that a bromine at the R6 position and/or hydrogen at the R9 position make the compound a better norepinephrine uptake inhibitor than a DA uptake inhibitor, whereas hydrogen at the R6 and/or a substituent larger than a propyl group at the R2 position make the compound a more potent DA uptake inhibitor. PMID- 8360833 TI - An interactive program for pharmacokinetic modeling. AB - A computer program, PharmK, was developed for pharmacokinetic modeling of experimental data. The program was written in C computer language based on the high-level user-interface Macintosh operating system. The intention was to provide a user-friendly tool for users of Macintosh computers. An interactive algorithm based on the exponential stripping method is used for the initial parameter estimation. Nonlinear pharmacokinetic model fitting is based on the maximum likelihood estimation method and is performed by the Levenberg-Marquardt method based on chi 2 criterion. Several methods are available to aid the evaluation of the fitting results. Pharmacokinetic data sets have been examined with the PharmK program, and the results are comparable with those obtained with other programs that are currently available for IBM PC-compatible and other types of computers. PMID- 8360832 TI - A multi-organ, axially distributed model of capillary permeability for a magnetic resonance imaging contrast agent. AB - Capillary permeability was resolved from uptake data for eight rat organs with gadoteridol, which is a stable, well-tolerated, nonionic, highly water soluble, gadolinium-containing, magnetic resonance imaging contrast agent. The extracellular kinetics were elucidated with an axially distributed, plasma interstitial fluid model and measured plasma flow, organ plasma volume, and interstitial fluid volume. The molecular and biological properties of gadoteridol and this kinetic model provide magnetic resonance imaging with a tool to begin measuring physiologic processes. PMID- 8360834 TI - Synthesis of potential metabolites of ethyl (E)-4-[2-(3,4-dihydro-4,4-dimethyl-2H 1-benzopyran-6-yl)-1-propenyl] benzoate. AB - Potential metabolites of ethyl (E)-4-[2-(3,4-dihydro-4,4-dimethyl-2H-1-benzopyran 6-yl)-1-propenyl] benzoate were synthesized. The new compounds include ethyl 3 [3,4-dihydro-4,4-dimethyl-2H-1-benzopyran-6-yl]crotonate, 3-[3,4-dihydro-4,4 dimethyl-1H-1-benzopyran-6-yl]crotonic acid, 3,4-dihydro-4,4-dimethyl-2H-1 benzopyran-6-carboxylic acid, 4-[3,4-dihydro-4,4-dimethyl-2H-1-benzopyran-6 yl]delta 2-butenolide, ethyl (E)-4-[3,4-dihydro-4,4-dimethyl-2H-1-benzopyran-6 yl)-3-hydroxy-1- propenyl]benzoate, ethyl (E)-4-[2-(3,4-dihydro-4,4-dimethyl-2H-1 benzopyran-6-yl)-2-propenal] benzoate, and ethyl (E)-4-[2-(3,4-dihydro-4,4 dimethyl-2H-1-benzopyran-6-yl)-2-propenoic+ ++ acid]benzoate. Stereospecific oxidizing reagents and/or conditions were developed for these sensitive systems and include the use of SeO2, Clorox bleach, activated MnO2, and NaClO2 in the presence of resorcinol as a chlorine scavenger. PMID- 8360835 TI - Population pharmacodynamic modeling of drug-induced anemia. PMID- 8360836 TI - Effect of electrolytes on oxygen solubility in aqueous systems. PMID- 8360837 TI - Skin penetration enhancement of triprolidine base by propylene glycol. PMID- 8360838 TI - Polylactide-polyglycolide delivery system for physostigmine. PMID- 8360839 TI - Simulation studies on ethanol metabolism in different human populations with a physiological pharmacokinetic model. AB - A physiological pharmacokinetic model of ethanol metabolism was used to simulate ethanol metabolism in standard, fasted, human males of the white American, white European, black American, and Japanese populations. Gastric ethanol metabolism accounted for only 0.24% of the dose in the several populations. In contrast, hepatic first-pass ethanol metabolism accounted for 3.7-4.2% of the dose. Ethanol elimination by the lung and kidney accounted for 1.3-1.7% of the dose in the several populations. The black American population had a significantly higher maximum blood ethanol concentration and area under the blood ethanol concentration versus time curve than the other populations studied when either a single dose or multiple doses of ethanol were ingested. These increases were due to the presence of a considerable amount of the beta 3 beta 3-alcohol dehydrogenase (ADH) isoenzyme, with a Michaelis constant of 34 mM in the black American population. The Japanese population, which has a relatively high proportion of the beta 2 beta 2-ADH isozyme, metabolized ethanol somewhat more rapidly than the other populations, as previously noted. PMID- 8360840 TI - Pharmacokinetics of the anticancer agent sulofenur in mice, rats, monkeys, and dogs. AB - The absorption and pharmacokinetics of sulofenur [N-(indan-5-sulfonyl)-N'-(4 chlorophenyl)urea, LY186641] and its major metabolites were examined in mice, rats, monkeys, and dogs. The compound is a diarylsulfonylurea currently being evaluated as an oncolytic agent in phase I and II trials. In all species, sulofenur was well absorbed after an oral dose, but over a prolonged period, and sulofenur exhibited a fairly long half-life of elimination from plasma. These values ranged from 6 h in rats up to 30, 110, and 200 h in mice, monkeys, and dogs, respectively, at doses (240-1000 mg/m2) within the range of those used in clinical trials. Experiments describing the high degree of binding of sulofenur to plasma proteins (consistently > 99%) help to explain these relatively long half-lives. There is, however, a large difference between these plasma half-lives in the species studied. Sulofenur was previously found to be extensively metabolized to products that are excreted primarily into the urine. In this study, its major metabolites, which are found mainly in the urine, were also minor components of the drug-related material (< 10% of the sulofenur concentrations) in the plasma of rats treated with sulofenur. The absorption, binding characteristics, and elimination of these major metabolites after their administration to rats were also compared with sulofenur.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8360841 TI - Kinetics and mechanisms of peptide aggregation. I: Aggregation of a cholecystokinin analogue. AB - Aggregation kinetics for a tetrapeptide analogue of cholecystokinin (A-71623) have been studied by quasi-elastic light scattering. Aggregation kinetics were quantitated with a kinetic model, described herein, which was modified for quasi elastic light scattering data. The model predicts that the average molecular weight of peptide aggregates increases in a linear fashion with time. Data generated for A-71623 were consistent with the model presented under conditions of varied ethanol concentration at a fixed peptide concentration, as well as varied A-71623 concentration at fixed ethanol concentration. Although not the primary thrust of this study, experimental design permitted some understanding of the effect of environmental changes on the apparent aggregation kinetics of A 71623. These studies suggest A-71623 aggregation may be partially mediated by hydrophobic bonding. PMID- 8360842 TI - Pharmacokinetics and metabolic interconversion of intravenous 4-amino-5-chloro-2 [(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide and its sulfide and sulfone metabolites in rats. AB - The pharmacokinetics of a new 5-hydroxytryptamine (5HT3) receptor antagonist, 4 amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide (ML 1035, 1), and its sulfone and sulfide metabolites were examined in 12 rats. Each of these compounds (25.4 mumol/kg) was administered to rats intravenously. Their plasma concentrations were measured by high-performance liquid chromatography. These plasma data revealed that 1, a sulfoxide, underwent interconversion with its sulfide metabolite. However, no interconversion was observed between 1 and its sulfone metabolite. Examination of mean times and additional properties of the 1/sulfide metabolite system revealed that total exposure times of 1 and the sulfide metabolite were moderately and weakly, respectively, influenced by the metabolic interconversion process. However, the tissue distribution process strongly influenced the total exposure times of both compounds. The disposition of the sulfone metabolite of 1 was also strongly influenced by the tissue distribution process. In addition, < 3% of the intravenous dose of 1 or the sulfide was available to the general circulation as the sulfone metabolite. PMID- 8360844 TI - Application of a system analysis approach to population pharmacokinetics and pharmacodynamics of nicardipine hydrochloride in healthy males. AB - Nicardipine hydrochloride, a dihydropyridine calcium channel blocker, possesses antihypertensive and arterial vasodilator properties. A system analysis approach, which makes fewer structural assumptions than compartmental methods, is presented for determining the pharmacokinetics and pharmacodynamics of nicardipine hydrochloride in healthy males following a discontinuous infusion at four dose levels. The results indicate that the average total body clearance of nicardipine is 0.920 L/h/kg and the volume of distribution is 0.275 L/kg. Nicardipine hydrochloride has a mean residence time in the body of 1.27 h, of which 0.324 h were spent in the systemic circulation and the remainder in the periphery. The determined pharmacokinetic model was linked to a pharmacodynamic model that allowed the change in the mean arterial blood pressure and heart rate to be described and predicted. A population pharmacokinetic-pharmacodynamic model was derived and the predictive power of the proposed model was assessed with a cross validation technique that employs a relative predictive quotient for comparing the predictions to the fitted model. The results indicate that the proposed model describes the pharmacodynamics of nicardipine in healthy males and has good predictive ability when tested with a cross-validation procedure. PMID- 8360843 TI - Toxin-targeted design for anticancer therapy. II: Preparation and biological comparison of different chemically linked gelonin-antibody conjugates. AB - To obtain more potent immunotoxins for anticancer therapy a gelonin-AR3 antibody immunoconjugate was prepared with different new linkers and coupling procedures. The gelonin was derivatized with the heterobifunctional thioimidate linkers ethyl acetyl-3-mercaptopropionthioimidate (AMPT) and 3-(4 carboxamidophenyldithio)propionthioimidate (CDPT), and with the succinimidyl type reagents N-succinimidyl-3-(4-carboxamidophenyldithio)propionate (SCDP) and N succinimidyl-S-acetyl thiolacetate (SATA). The biological activity of gelonin modified with different linkers (AMPT, CDPT, SCDP, SATA) was determined by a rabbit reticulocyte assay. We found that AMPT was the molecule of choice to derivatize the toxin, confirming the preferability of thioimidate linkers. The monoclonal antibody Mab was derivatized with CDPT and SCDP. Then the following immunoconjugates were prepared with different procedures: Mab-CDPT with gelonin AMPT; Mab-CDPT with gelonin-CDPT; Mab-SCDP with gelonin-SATA. To verify whether selection of the most suitable coupling procedure could affect the antitumoral activity of the gelonin-AR3 immunoconjugate, the three immunotoxins were tested on target HT-29 human colon carcinoma cells versus nontarget MeWo cells. The gelonin immunoconjugate linked via the AMPT-CDPT thioimidate reagents showed highest antitumoral activity as well as best selectivity for the target cells. PMID- 8360845 TI - A rapid method for the measurement of cholesterol thermodynamic activity in bile salt-lecithin-cholesterol solutions. AB - Earlier work from this laboratory suggested that the cholesterol (Ch) thermodynamic activity is a more meaningful measure of the degree of Ch supersaturation in human bile than the widely known cholesterol saturation index. An early version of a method for determining thermodynamic activity based on Ch uptake from bile salt (BS)-lecithin (LE) solutions into silicone polymer particles, but requiring 12-24 h for reaching equilibrium, was considered unsatisfactory because Ch nucleation and crystal formation frequently occurred within a few hours. The aim of the present work was to develop a method that would reduce equilibration times to the order of 1 h. Changing the thickness of the silicone film alone did not result in the desired reduction of equilibration times and it was soon deduced that the uptake of Ch by the silicone film from the BS-LE solution was a surface-controlled transport process involving the transport of Ch by negatively charged BS and BS-LE micelles at the interface. Three different approaches were tried to modify the silicone film to make its surface positively charged, thereby reducing and/or eliminating the presumed electrical repulsion barrier for the interfacial transport of Ch. The film was treated with different concentrations of aminopropyl methyl-dimethylsiloxane (AMDS) in cyclohexane, octadecyldimethyl-[3-(trimethoxysilyl)-propyl] ammonium chloride (ODTOP) in methanol, and octadecylamine solution in ethanol. Films treated with 1 1.5% ODTOP and 5-10% AMDS reduced the Ch equilibration times for model BS-LE solutions to < 1 h. PMID- 8360846 TI - Nutrient-induced changes in the permeability of the rat jejunal mucosa. AB - We examined the site of action of nutrients that enhance mucosal permeability by use of D-glucose as an archetype of nutrients of this class. We tested the hypothesis that D-glucose enhances mucosal permeability by either acting outside the intestinal lumen after absorption or acting inside the intestinal lumen to cause mediator release from either endocrine or nerve tissue. The rate of absorption of L-[14C]glucose, a passively absorbed molecule, from the lumen was used as an index of the permeability of the mucosa of a perfused segment. L Glucose was absorbed more rapidly in the presence of D-glucose than in the presence of an equimolar concentration of mannitol. However, the permeability of the jejunal mucosa was unaffected by elevated blood glucose levels during intravenous infusion of D-glucose. The mucosal permeability was also unaffected by exposure of an adjacent segment to D-glucose, a result suggesting that D glucose does not alter mucosal permeability by inducing the release of a blood borne mediator from enteroendocrine cells. Finally, the effect of D-glucose on mucosal permeability could not be blocked by hexamethonium or tetrodotoxin, a result suggesting that the intestinal nerves do not mediate this phenomenon. Lidocaine significantly increased the rate of L-glucose absorption when D-glucose was present in the lumen but had no effect on L-glucose absorption under basal conditions. Our findings indicate that D-glucose must be in contact with the apical membranes of enterocytes to alter mucosal permeability. This suggestion is consistent with the hypothesis that the modulation of mucosal permeability results from the activation of sodium-dependent cotransport systems. PMID- 8360847 TI - Pharmacokinetics of (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt and (Me)Arg-Lys-Pro-Trp tert-Leu-Leu administered intravenously to beagle dogs. AB - The pharmacokinetics of two analogues (NT-1 and NT-2) of the smallest active fragment of neurotensin were investigated in beagle dogs after intravenous (iv) administration at the doses of 0.1 and 0.5 mg/kg for NT-1 and of 0.25 and 0.5 mg/kg for NT-2. After iv administration of these two drugs, the plasma levels decreased with time with a biexponential pattern, and linear kinetic behavior was observed. The pharmacokinetic parameters (mean +/- standard error of mean) after iv administration of NT-1 at 0.1 mg/kg were as follows: the half-life of the distribution phase (t1/2 alpha) was 0.29 +/- 0.11 h, the half-life of the terminal phase (t1/2 beta) was 1.99 +/- 0.41 h, total plasma clearance (CL) was 33.2 +/- 6.3 mL/h/kg, steady-state volume of distribution (Vdss) was 57.1 +/- 2.8 mL/kg, and mean residence time (MRT) was 2.20 +/- 0.55 h. The t1/2 alpha, t1/2 beta, CL, Vdss, and MRT values after iv administration of NT-2 at 0.25 mg/kg were 0.11 +/- 0.02 h, 0.58 +/- 0.04 h, 257.3 +/- 17.2 mL/h/kg, 180.3 +/- 4.6 mL/kg, and 0.71 +/- 0.04 h, respectively. After iv administration of NT-1, NT-2 was detected in the plasma. It was confirmed from this result that NT-1 was metabolically hydrolyzed to NT-2 in the body of beagle dog. PMID- 8360848 TI - Solvent dependence of optical rotation of (S)-N-[1-(2-fluorophenyl)- 3,4,6,7 tetrahydro-4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2 carboxamide. AB - A new cholecystokinin-A antagonist, (S)-N-[1-(2-fluorophenyl)- 3,4,6,7-tetrahydro 4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2-carboxamide (FR120480; 1), is a chiral compound that shows considerable solvent dependence of its optical rotation. Not only the absolute values, but also the signs (+ or -) for this compound change in various solvents. The optical rotation of 1 inherently correlated to the electron donating property characterized by donor number of the solvent. The 1H NMR study implied that hydrogen bonds were formed between electron donor groups of the solvents and the NH groups of indole and amide of 1. In accordance with the NMR results, X-ray crystallography of the tetrahydrofuran solvate of 1 showed that hydrogen bond formation occurred between the oxygen atom of tetrahydrofuran and the amide group of 1. PMID- 8360849 TI - Use of hydroxypropyl methylcellulose acetate succinate in an enteric polymer matrix to design controlled-release tablets of amoxicillin trihydrate. AB - A controlled-release table of amoxicillin trihydrate was developed by use of a matrix formulation based on the enteric polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). Sustained drug release was shown by in vitro dissolution testing; the polymer could suppress drug release in the presence of gastric pH but could enhance drug release in the presence of small intestinal pH, compared with compacts of pure drug. Grinding or physical mixing of the drug with the polymer, an alteration in normal compaction pressure, or a substitution of other enteric polymers did not markedly affect drug release from compacts. Physicochemical testing of samples confirmed that the method of mixing did not alter powder morphology. An ethanolic granulation procedure was used in the production of final tablets (21 x 10 mm) containing amoxicillin (750 mg), HPMCAS, anhydrous directly compressible lactose, and lubricants. These large tablets showed a promising sustained-release effect in vitro when a variable-pH-shift dissolution procedure was used. However, single-dose studies with a panel of fasting subjects showed that the tablets had a relative bioavailability of only 64.4%. Other pharmacokinetic parameters confirmed a lack of therapeutic advantage of these tablets over an equivalent dose of conventional capsules. PMID- 8360850 TI - Mechanism of phosphate adsorption to a three-dimensional structure of boehmite in the presence of bovine serum albumin. AB - A new microcrystalline boehmite (tentatively named PT-A) was synthesized as an efficient phosphate adsorbent to replace aluminum hydroxide gel. The characteristic structure of PT-A was examined by nitrogen adsorption/desorption, X-ray diffraction, deviation microscopy, and scanning electron microscopy to establish a pore structural model of PT-A. With this model structure, the details of the mechanism of interaction between PT-A and phosphate in the presence of bovine serum albumin (BSA) are discussed. PT-A is a spherical particle with a diameter of approximately 100 microns and a porous surface structure, and its inside is packed with boehmite microcrystals (crystallite size, 2 nm). PT-A has three types of pores in its structure: a micropore with a narrow size distribution, a mesopore with a broad size-distribution, and a macropore (radii of pores are 0.7, 1-20, and approximately 300 nm, respectively). When phosphate was incubated with PT-A in human gastric and intestinal juices or in an aqueous solution containing BSA, the amounts of phosphate adsorbed by PT-A were not affected by the presence of proteins. The nitrogen adsorption/desorption isotherms and energy dispersive X-ray analyses demonstrated that phosphate could diffuse to the smaller tunnels freely even if the external surface of PT-A was covered with BSA. It was also demonstrated that the main site of adsorption for phosphate was in micropores of PT-A, whereas BSA was adsorbed only to the external surface and none entered inside smaller tunnels consisting of micro- and mesopores. PMID- 8360851 TI - Multiple-layer, direct-compression, controlled-release system: in vitro and in vivo evaluation. AB - A new approach to achieve controlled drug delivery is demonstrated for a triple layer tablet, which simultaneously combines the principles of diffusion and dissolution. Heckel's equation was used to characterize the compression behavior of formulation components. A balanced proportion of each component and a model drug (theophylline) were selected to avoid lamination after ejection and ensure coherent compaction. In vitro release profiles over a period of 10 h in different dissolution media and hydrodynamic conditions were similar and resulted in an n value of 0.786, signifying anomalous release kinetics. The n value is calculated from a curve fit to the empirical equation: Mt/Minfinity = Ktn, where Mt and Minfinity denote the amount of drug released at time t and at infinite time, respectively, K denotes the proportionality constant, and n characterizes the type of release mechanism operative during the dissolution process. In vivo study in human subjects after administration of the experimental triple-layer system exhibited a steady rise in plasma concentration up to 7 h. The actual amount of drug absorbed by the body was calculated by the Wagner-Nelson technique, and a linear relationship was observed between the percentage absorbed in vivo and the percentage dissolved in vitro. The proposed triple-layer model appears to provide good correlation between in vitro and in vivo results with maximum flexibility with respect of dose, duration range, and ease of production. PMID- 8360852 TI - Antibacterial organophosphorus compounds: phosphoranilidohydrazones of 5-nitro-2 furaldehyde. AB - A series of phosphoranilidohydrazones of 5-nitro-2-furaldehyde was synthesized and evaluated for antibacterial activity. The series was prepared to examine the applicability of phosphoramidic hydrazones as carriers for the antibacterial nitrofuran moiety. Designed as analogues of nitrofurantoin, members of the series were chosen according to the Topliss approach to analogue design. The title compounds were devoid of gram-negative activity but possessed moderate antistaphylococcal activity. The most potent members of the series were equipotent with nitrofurantoin against Staphylococcus aureus. The relationship between structure and antistaphylococcal activity is discussed. PMID- 8360853 TI - Phase diagram of (R)- and (S)-4-hydroxy-2-pyrrolidone mixtures: a new case of a conglomerate-forming system. AB - The phase diagram of (R)- and (S)-4-hydroxy-2-pyrrolidone presents a conglomerate in the racemic mixture. The enthalpy of melting extrapolated by the Schroder-van Laar-Le Chatelier equation [change in enthalpy (delta H) = 28410 J/mol; melting temperature (TA) = 429.9 K; solidus temperature (Ts) = 395.4 K] and the value determined by differential scanning calorimetry (delta H = 28494 J/mol; TA = 429.6 K; Ts = 394.6 K) are in excellent agreement. The experimental entropy of the mixing of enantiomers is 5.69 J/mol.K. The conglomerate nature of the racemic mixture was confirmed by X-ray and IR spectroscopy. The presence of solvates was also observed. PMID- 8360854 TI - Estimation of variance for AUC in animal studies. PMID- 8360855 TI - A method for continuous pH regulation of dissolution medium in stirred vessels. PMID- 8360856 TI - Adenylate cyclase-the more membrane associated, the less radiosensitive. AB - A dose dependent but not parallel decreases were observed both in SH content and catalytic activity of "free" catalytic subunit after irradiation (0-3200 Gy), while SH groups of membrane-associated adenylate cyclase were insensitive (under 3200 Gy). An initial "radioactivation" of membrane-associated enzyme was found under 800 Gy, then an inhibition above 1600 Gy. The SH alkylating agent, N ethylmaleimide resulted in a complete inactivation, both of membrane associated form of adenylate cyclase and "free" catalytic subunit with similar inactivation profiles. These data indicate that in the radiosensitivity or "radioprotection" of adenylate cyclase, its membrane association/integration might play a more important role than the SH groups themselves. PMID- 8360857 TI - A shuttle vector system for studying ionizing radiation-induced mutagenesis in mammalian cells. AB - A shuttle vector system was developed to quantitate and analyze ionizing radiation-induced mutation in mammalian host cells, COS-1 and CV-1. The shuttle vector pSV2-lacY, which was constructed to detect both point mutations and deletions, was irradiated in vitro with 60Co gamma rays before introduction into unirradiated host cells. The plasmid was then isolated and reintroduced into HB101 (lacY-) bacterial host cells for identification of mutated lacY marker genes. Gamma-irradiation produced a decrease of the survival (recovery) and an increase of mutation of the shuttle vector. The mutated shuttle vector molecules were examined for structural changes by means of restriction endonuclease digestion and agarose gel electrophoresis. A dose dependent increase was observed in the percentages of gross alteration events of total mutations in mammalian host. This system will be useful for studies of ionizing radiation-induced mutagenesis. PMID- 8360858 TI - Transfer of 239Pu to mouse fetoplacental tissues. AB - Cross-placental transfer of 239Pu from the mother to fetus was studied in C3H mice. The activity of 239Pu in the conceptus was measured 24 hrs after the intravenous injection of 239Pu citrate on days 10.5 to 16.5 of gestation. More 239Pu was transferred to the conceptus when the plutonium was administered in the later stages of gestation; 0.12% of the injected dose per conceptus on day 10.5 and 1.3% on day 16.5. In all the gestational stages examined, the yolk sac and decidua contained more than 89% of the total activity distributed in the conceptus. The concentration of 239Pu in the yolk sac was about two orders of magnitude greater than that in the fetus. The 239Pu concentration in the maternal liver decreased with the gestational stage. In the early gestational stages the concentration in the maternal liver was greater than that in the yolk sac; but, this relationship was reversed in the later stages. PMID- 8360859 TI - X-irradiation-induced emesis in Suncus murinus. AB - X-irradiation-induced emesis was investigated in Suncus murinus, a house musk shrew. Whole body X-irradiation caused emesis, and the calculated ED50 value that induced emesis in 50% of animals was 429 cGy. At the irradiation dose of 800 cGy all the animals vomited 10.0 +/- 2.4 times with a latency of 20.0 +/- 2.9 min. The emetogenic effect of X-irradiation was dependent on the part of the body exposed. Abdominal X-irradiation at 1000 cGy caused emesis in all animals studied, whereas the same dose to the head had no emetogenic effect. We investigated several prophylactic methods against X-irradiation-induced emesis. Surgical vagotomy completely inhibited the emesis induced by 800 cGy X irradiation. Emesis was also prevented by the subcutaneous administration of tropisetron (ICS 205-930, a selective serotonergic 5-HT3 receptor antagonist) with an ID50 value of 29 micrograms/kg. These results suggest that (1) suncus is a useful experimental animal for the study of radiation-induced emesis and the development of prophylactic drugs, (2) serotonin plays an important role in X irradiation-induced emesis, and (3) X-irradiation-induced emesis is very similar to that caused by cancer chemotherapeutic agents. PMID- 8360860 TI - Effect of gamma-irradiation on the uptake and digestion of 125I-labeled bovine serum albumin by rat visceral yolk sac cultured in vitro. AB - The effect of gamma-irradiation on a major nutritional function of the yolk sac (the uptake and digestion of macromolecular materials) was studied in rat visceral yolk sacs cultured in vitro being used 125I-labeled bovine serum albumin (RISA) as the tracer protein. The uptake of RISA (per g wet weight) by rat yolk sacs irradiated with doses of 5-80 Gy was essentially the same as that in the unirradiated control yolk sacs. There were no significant differences in yolk sac uptake of RISA with respect to the radiation doses or to culture period up to 18 hours after irradiation. External gamma-irradiation with 10-80 Gy does also had no effect on the extracellular release of 125I from yolk sacs which had been taken it up as RISA. The ratios of the activity in ultrafiltrates of the medium to the total activity in the medium were slightly higher at doses of 40 and 80 Gy. PMID- 8360861 TI - [Significance of ultrasonographic aspects of hydatid cyst of the liver. Apropos of a case studied before and after liver injury]. PMID- 8360862 TI - [Ascariasis of the common bile duct. An ultrasonographic case in Yemen]. AB - A case of a biliary ascariasis associated with a cystic bile duct lithiasis observed in the French Medical Mission of the Republic of Yemen is reported. Ascaris biliary migration, method of diagnosis, complications and treatment are reviewed. PMID- 8360863 TI - [Percutaneous treatment of liver abscess. Apropos of 34 cases]. AB - The authors report on a retrospective series of 37 liver abscesses treated via the percutaneous route in 34 patients, in order to assess the efficacy of this method. One or more aspiration punctures were undertaken in 24 patients (70.6%), while percutaneous drainage was performed in 10 patients (29.4%). In 27 cases (79.5%), this percutaneous treatment resulted in a cure. Further surgical drainage, carried out in 7 patients (20.5%) was only required in 3 cases, twice due to the inefficacy of percutaneous drainage and once in the presence of three liver abscesses containing particularly thick pus. Ultrasonographic monitoring demonstrated a return to normal in 66.6% of cases, the persistence of a slight residual collection in 26.6% patients and one relapse, two months after percutaneous drainage. Two complications inherent to the percutaneous treatment were noted: a pneumothorax and a case of septicemia, both of which had a favourable outcome. PMID- 8360864 TI - [Primary carcinoid tumor of the pancreas. X-ray computed tomographic and echo endoscopic aspects]. AB - Primary carcinoid tumors of the pancreas are exceedingly rare, only few cases have been reported in the literature. We present a case of primary carcinoid tumor of the pancreas occurring on chronic pancreatitis. The CT, as well as endosonographic features are described. Those two techniques might contribute to an early preoperative diagnosis which is important since carcinoid tumors have a better prognosis than the common pancreatic adenocarcinoma. PMID- 8360865 TI - [Cystic dilatation of the seminal vesicle associated with renal agenesis. Contribution of different types of imaging]. AB - The authors report a case of cystic disease of the seminal vesicle associated with renal agenesis. This young patient presented only with cystitis. Developmental malformation of the mesonephric duct is the cause of this uncommon abnormality. The value of modern imaging (IVU, US, CT, MRI) is related. PMID- 8360866 TI - [Normal and pathologic imaging of the pituitary stalk]. AB - Study of the pituitary stalk pathology about six demonstrative cases. This illustrative cases are described after review of literature, anatomy and imaging modalities. CT and MRI are very sensitive technics but not very specific. PMID- 8360868 TI - [Radiology in Cambodia]. PMID- 8360867 TI - [Cauda equina syndrome disclosing adenocarcinoma of the ethmoid]. AB - Cauda equina metastases have been exceptionally described in sinusal neoplasms. MRI with gadolinium injection show up the primitive lesion and its neurologic extension. We report a case of cauda equina syndrome in which, only MRI, had show up intradural metastases and localised the ethmoid sinus carcinoma. PMID- 8360869 TI - [In Uruguay, the Leborgne family]. PMID- 8360870 TI - Anticonvulsant activities of some arylsemicarbazones displaying potent oral activity in the maximal electroshock screen in rats accompanied by high protection indices. AB - Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens accompanied by neurotoxicity when given to mice by the intraperitoneal route. However quantitative data revealed protection indices (TD50/ED50) of less than 4 in general. Oral administration of the compounds to rats led to excellent potency in the MES screen accompanied by high protection indices while virtually no activity in the scPTZ test was displayed. These observations support the theory that one large hydrophobic group (in this case the aryl ring) and two electron donor atoms (present in the semicarbazono group) are requirements for protection in the MES screen. In general, the semicarbazones had rapid onsets of action, and one of the ways in which these compounds displayed their anticonvulsant activity is likely to be interaction with chloride channels. Empirical and semiempirical conformational calculations indicated that certain molecular fragments and hydrophobicity of these molecules affect bioactivity. PMID- 8360871 TI - Nonpeptide angiotensin II receptor antagonists. 2. Design, synthesis, and structure-activity relationships of 2-alkyl-4-(1H-pyrrol-1-yl)-1H-imidazole derivatives: profile of 2-propyl-1-[[2'-(1H-tetrazol-5-yl)-[1,1' -biphenyl]-4-yl] methyl]-4-[2-(trifluoroacetyl)-1H-pyrrol-1-yl]-1H- imidazole-5-carboxylic acid (CI-996). AB - A novel series of nonpeptide angiotensin II (AII) receptor antagonists containing a 1H-pyrrol-1-yl moiety at the 4-position of the imidazole have been developed. The pyrrole group occupies the same lipophilic pocket at the receptor as the chloro group in DuP 753 (68) and EXP 3174 (69) and the pentafluoro group in DuP 532 (70), respectively. The impetus for its selection came from bioisosteric considerations based on hydrophobic and electronic substituent constants. An extensive study of the structure-activity relationships revealed several highly potent AII receptor antagonists. An acyl substitution at the 2-position of the pyrrole ring improved activity, most notably in the in vivo rat model. In addition, the 2-substituted pyrrole compounds improved chemical stability toward extremely facile decarboxylation reaction associated with unsubstituted pyrrole analogues, thus facilitating development of these agents. The IC50's of 18, 20, and 42 (< 1 nM) were better than the reference compounds 69 and 70, respectively. These compounds were selective AII antagonists that compete at the AT1 receptor and showed no affinity at the AT2 receptor at concentrations up to 10 microM. Upon intravenous administration in a normotensive rat model, compound 18 inhibited the AII-induced responses with ED50 of 6 micrograms/kg per min. In a renal hypertensive rat model, the antihypertensive potency of compound 18, at a dose of 10 mg/kg, was very similar to those 68 and 69, respectively. Compound 18 demonstrated a dose-related (3-30 mg/kg) decrease in blood pressure that was sustained for greater than 24 h. On the basis of its profile, compound 18, designated as CI-996, has been selected for in-depth studies. The design, synthesis, in vitro, and in vivo structure-activity relationships are described. PMID- 8360872 TI - Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin-1(2H)-ones. AB - The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p-aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 microM. PMID- 8360873 TI - Synthesis and structure-activity studies of a series of spirooxazolidine-2,4 diones: 4-oxa analogues of the muscarinic agonist 2-ethyl-8-methyl-2,8 diazaspiro[4.5]decane-1,3-dione. AB - A series of spirooxazolidine-2,4-dione derivatives related to the putative M1 agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8 methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs. PMID- 8360874 TI - Potent HIV protease inhibitors: the development of tetrahydrofuranylglycines as novel P2-ligands and pyrazine amides as P3-ligands. AB - A series of protease inhibitors bearing constrained unnatural amino acids at the P2-position and novel heterocycles at the P3-position of compound 1 (Ro 31-8959) were synthesized, and their in vitro enzyme inhibitory and antiviral activities were evaluated. Replacement of P2-asparagine of compound 1 with (2S,3'R) tetrahydrofuranylglycine resulted in improvement in enzyme inhibitory as well as antiviral potencies (compound 23). Interestingly, incorporation of (2S,3'S) tetrahydrofuranylglycine at the P2-position proved to be less effective. The resulting compound 24 was 100-fold less potent than the 2S,3R-isomer (compound 23). This stereochemical preference indicated a hydrogen-bonding interaction between the tetrahydrofuranyl oxygen and the residues of the S2-region of the enzyme active site. Furthermore, replacement of P3-quinolinoyl ligand of 1 with various novel heterocycles resulted in potent inhibitors of HIV proteases. Of particular interest, compound 2 with (2S,3'R)-tetrahydrofuranylglycine at P2 and pyrazine derivative at P3 is one of the most potent inhibitors of HIV-1 (IC50 value 0.07 nM) and HIV-2 (IC50 value 0.18 nM) proteases. Another important result in this series is the identification of compound 27 in which the P2-P3-amide carbonyl has been removed. The resulting compound 27 has exhibited improvement in antiviral potency while retaining the enzyme inhibitory potency similar to compound 1. PMID- 8360875 TI - Synthesis and evaluation of conformationally restricted N-[2-(3,4 dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamines at sigma receptors. 2. Piperazines, bicyclic amines, bridged bicyclic amines, and miscellaneous compounds. AB - As a continuation of our earlier study (J. Med. Chem. 1992, 35, 4334-4343) we conformationally restricted the sigma-receptor ligand 2-(1-pyrrolidinyl)-N-[2 (3,4-dichlorophenyl)ethyl]-N-methylethylamine (1) by incorporating it into a series of homologous piperazines 3-9 and homopiperazines 10 and 11, diazabicyclononanes and decanes, bridgehead bicyclooctanes and nonanes as well as other miscellaneous compounds. sigma-Receptor binding affinities were obtained using [3H](+)-pentazocine in guinea pig brain membrane sigma 1 sites. The studies suggest that the nitrogen lone pair orientation found in the piperazines affords the strongest binding interaction. Other nitrogen lone pair orientations or compounds representing unlikely staggered conformations of 1 [ as in 4-[2-(3,4 dichlorophenyl)ethyl]-1,4-diazabicyclo[3.2.2]nonane (16)] show very weak sigma interaction. Comparison of the binding data of different N-substituted homologues of 1 with those of the 1-[2-(3,4-dichlorophenyl)ethyl]-4-alkylpiperazines suggests that the two nitrogen atoms of 1 are working in opposition to one another in terms of their sensitivity to steric bulk. The high binding affinity of the 1,4-diazabicyclo[4.3.0]nonanes 12 suggests that these may approximate the methyl and pyrrolidine ring conformations found in 1 when it is bound to the sigma receptor. Compound 12 exhibited a 4-fold enantioselectivity favoring (+) 12. The synthesis of 6,7-dichloro-2-[[2-(1-pyrrolidinyl)ethyl]amino]tetralin (19) and its desmethyl derivative 20 permitted constraint of the 3,4-dichlorophenyl and N-methyl moieties of 1 into a gauche orientation. The binding data suggests that this conformation in 1 favors strong binding interaction at sigma-receptors. sigma-Receptor Ki's ranged from 0.55 nM for 1-[2-(3,4-dichlorophenyl)ethyl]-4-n butylpiperazine (7) to 654 nM for 16. Overall comparison of the results indicate that 1 is subject to considerable conformational freedom and suggests that the sigma receptor is not subject to rigid stereochemical restraints with 1. These results add to our earlier study where we restrained 1 using simple monocyclic heterocycles. PMID- 8360876 TI - A novel constrained reduced-amide inhibitor of HIV-1 protease derived from the sequential incorporation of gamma-turn mimetics into a model substrate. AB - C7 mimetics, designed to lock three amino acid residues of a peptide chain into a gamma-turn conformation, were introduced sequentially between the P3 to P2' positions of a model HIV-1 protease substrate I (resulting in compounds II-IV) to probe its conformational requirements in binding to HIV-1 protease. Of these, compound IIIa with the C7 mimetic replacing Asn-Tyr-Pro, corresponding to the P2 through P1' positions of substrate, was found to be an inhibitor with a Ki of 147 microM. Reduction of the amide bond in the C7 mimetic of IIIa resulted in a novel constrained reduced-amide mimetic VIa with a Ki of 430 nM. This corresponds to over a 300-fold improvement in inhibitory activity over the original C7 mimetic. The inhibitory activity of mimetic VIa was in addition found to be 44-fold better than a similar linear reduced-amide containing inhibitor V. The synthesis of these mimetics are described. PMID- 8360877 TI - Synthesis and anaerobic activity of novel 1-carba-1-dethiacephalosporins. AB - The synthesis and biological evaluation of novel 1-carba-1-dethiacephalosporins exhibiting activity against anaerobic pathogens are described. The nitrothiazole substituent was determined to be crucial to maintaining this activity. The pharmacokinetic parameters and initial toxicological profile of the lead compound are discussed. PMID- 8360878 TI - Quinoxaline N-oxide containing potent angiotensin II receptor antagonists: synthesis, biological properties, and structure-activity relationships. AB - A series of novel quinoxaline heterocycle containing angiotensin II receptor antagonist analogs were prepared. This heterocycle was coupled to the biphenyl moiety via an oxygen atom linker instead of a carbon atom. Many of these analogs exhibit very potent activity and long duration of effect. Interestingly, the N oxide quinoxaline analog was more potent than the nonoxidized quinoxaline as in the comparison of compounds 5 vs 30. In order to improve oral activity, the carboxylic acid function of these compounds was converted to the double ester. This change did result in an improvement in oral activity as represented by compound 44. PMID- 8360879 TI - Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of potential prodrugs of benzimidazole-7-carboxylic acids. AB - In order to improve the oral bioavailability (BA) of 2-butyl-1-[[2'-(1H-tetrazol 5-yl)biphenyl-4-yl]methyl]-1H-benzimid azole - 7-carboxylic acid (3: CV-11194) and 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl]-1H-benzimidazole-7 carboxylic acid (4: CV-11974), novel angiotensin II (AII) receptor antagonists, chemical modification to yield prodrugs has been examined. After selective tritylation of the tetrazole rings in 3 and 4, treatment of N-tritylated benzimidazole-7-carboxylic acids (6, 7) with a variety of alkyl halides, followed by deprotection with hydrochloric acid, afforded esters of 3 and 4. Mainly 1 (acyloxy)alkyl esters and 1-[(alkoxycarbonyl)oxy]alkyl esters, double ester derivatives, were synthesized. Their inhibitory effect on AII-induced pressor response in rats and oral BA were investigated. (Pivaloyloxy)methyl and (+/-)-1 [[(cyclohexyloxy)-carbonyl]oxy]ethyl esters of 3 and 4 showed marked increases in oral bioavailability which significantly potentiated the inhibitory effect of the parent compounds on AII-induced pressor response. Among them, (+/-)-1 [[(cyclohexyloxy)carbonyl]oxy]ethyl 2- ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4 yl]methyl]-1H-benzimida zole- 7-carboxylate (10s, TCV-116) was selected as a candidate for clinical evaluation. PMID- 8360880 TI - Characterization of the interaction between human alpha-thrombin and methyl 3-(2 methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carboxylate (LY806303) using electrospray mass spectrometry and tandem mass spectrometry. AB - Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of action was never fully defined. Using ESI-MS, it is shown that inhibitor 1 covalently modifies human alpha-thrombin as evidenced by a shift in the molecular weight of the native protein by 72 Da, which is consistent with isobutyrylation (C4H7O; 71 Da) of the enzyme at a single site. Tryptic digestion of the modified protein and tandem mass spectral analysis of isolated peptide fragments indicate that compound 1 acylates Ser-205 of the heavy chain of alpha-thrombin. Ser-205, along with His-43 and Asp-99 make up the catalytic triad within the active site of thrombin. PMID- 8360881 TI - Analogues of capsaicin with agonist activity as novel analgesic agents; structure activity studies. 1. The aromatic "A-region". AB - A series of analogues of capsaicin, the pungent principle of chilli peppers, was synthesized and tested in assays for capsaicin-like agonism in vitro. The results of these assays were compared with activities in an acute nociceptive model and a correlation was observed which established that the results of these in vitro assays were predictive of analgesia. Using a modular approach the structure activity profile of specific regions of capsaicin congeners was established using an in vitro assay measuring 45Ca2+ uptake into neonatal rat dorsal root ganglia neurones. Substituted benzylnonanamides 2a-z and N-octyl-substituted phenylacetamides 4a-v were made to test the requirements for activity in the aromatic "A-region" of the molecule. Compounds with the natural substitution pattern (2b and 4c) and the corresponding catechols (2i and 4g) were the most potent, although the catechols were less potent in vivo. Other substitution patterns have reduced activity. These results have established stringent structural requirements for capsaicin-like activity in this part of the molecule. PMID- 8360882 TI - Analogues of capsaicin with agonist activity as novel analgesic agents; structure activity studies. 2. The amide bond "B-region". AB - A series of compounds incorporating replacements for the amide bond "B-region" moiety of capsaicin have been synthesized, including vanillylamides and esters, homovanillic acid amides and esters, ureas, and thioureas. These have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), which is predictive of analgesic activity, to investigate the requirements in this region of capsaicin for activity. N-(4-Hydroxy-3 methoxybenzyl)-N'-octylthiourea (14a) emerged as the most potent analogue (EC50 = 0.06 microM). An operational model based on multiple hydrogen-bonding interactions is proposed to explain the structure-activity profile observed. In combination with studies on the other regions of the capsaicin molecule these results describe a picture of the molecular interactions of capsaicin with its putative receptor. PMID- 8360883 TI - Analogues of capsaicin with agonist activity as novel analgesic agents; structure activity studies. 3. The hydrophobic side-chain "C-region". AB - Structural variants of the hydrophobic side chain ("C region") of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, < 55) in order to obtain high potency. Combination of the information gained here about the "C-region" of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency. PMID- 8360884 TI - Three-dimensional quantitative structure-activity relationship of angiotesin converting enzyme and thermolysin inhibitors. II. A comparison of CoMFA models incorporating molecular orbital fields and desolvation free energies based on active-analog and complementary-receptor-field alignment rules. AB - The utility of comparative molecular field analysis (CoMFA), a three-dimensional Quantitative Structure-Activity Relationship (3-D QSAR) paradigm, as a tool to aid in the development of predictive models has been previously addressed (Depriest, S.D. et al., J. Am. Chem. Soc. 1993, in press). Although predictive correlations were obtained for angiotensin-converting and thermolysin inhibitors, certain inadequacies of the CoMFA technique were noted. Primarily, CoMFA steric and electrostatic fields alone do not fully characterize the zinc-ligand interaction. Previously, this was partially rectified by the inclusion of indicator variables into the QSAR table to designate the class of zinc-binding ligand. Recent advances in molecular modeling technology have allowed us to further address this limitation of the preceding study. Using molecular orbital fields derived from semiempirical calculations as additional descriptors in the QSAR table, predictive correlations were produced based on CoMFA and molecular orbital fields alone--indicator variables no longer being necessary. Arbitrary information concerning the alignment of molecules under study within the active site introduces ambiguities into the CoMFA study. Crystallographic information detailing the binding mode of several thermolysin enzyme inhibitors has previously been used as a guide for the alignment of additional, noncrystallized, inhibitors. However, this process was complicated by the lack of parameters for zinc in the molecular mechanical force field. Therefore, zinc-ligand interactions were ignored during the standard minimization procedure. The use of field-fit minimization using complementary receptor fields as templates is presented as a possible solution to the problem. Predictive correlations were obtained from analyses based on this method of molecular alignment. The availability of crystallographic data for thermolysin enzyme-inhibitor complexes allowed for an alternate definition of the CoMFA region. Herein, promising results from analyses using actual receptor active-site atom probe atoms are presented. PMID- 8360885 TI - Synthesis of new 11 beta-substituted spirolactone derivatives. Relationship with affinity for mineralocorticoid and glucocorticoid receptors. AB - Various steroidal 17-spirolactones substituted in the 11 beta-position were synthesized to study the relationship between the nature of the 11 beta-arm and their affinity for cytosolic mineralocorticoid (MR) and glucocorticoid (GR) receptors prepared from adrenalectomized rabbit kidney or liver. One of them, the 11 beta-allenyl-3-oxo-19-nor-17-pregna-4,9-diene-21,17- carbolactone derivative, exhibited the same affinity for MR as aldosterone and a 5-fold higher affinity than mespirenone. Its affinity for GR was found to be relatively low. As suggested by molecular modeling, the marked differences in mineralocorticoid receptor binding affinity could be related to the structural features induced by this 11 beta-allenic substituent. PMID- 8360886 TI - A mechanism-based inactivation study of neutral endopeptidase 24.11. AB - The mechanism-based inactivation of human neutral endopeptidase 24.11 (NEP) was studied with N-[(R)-2-benzyl-5-cyano-4-oxopentanoyl]-L-phenylalanine (1) and its peptidic analogue, N(-)[N-(cyanoacetyl)-L-phenylalanyl]-L-phenylalanine (2). While both these active-site-directed molecules inactivate NEP, the related angiotensin-converting enzyme (ACE) is only inactivated by compound 2 [Ghosh et al. J. Med. Chem. 1992, 35, 4175-4179]. The selectivity in inactivation was addressed further by a comparative study of the interaction of compounds 1 and 2 with five other zinc proteases. The selective inactivation of NEP observed with the ketomethylene compound 1 suggests that the active site of NEP is less discriminating in its requirements for binding such substrate analogues as compared to ACE, a characteristic that may be exploited for designing specific mechanism-based inactivators for NEP. It is proposed that the inactivation is a result of NEP-catalyzed formation of ketenimine intermediates, which are subsequently trapped by an active-site nucleophile. PMID- 8360887 TI - Synthesis and kappa-opioid antagonist selectivity of a norbinaltorphimine congener. Identification of the address moiety required for kappa-antagonist activity. AB - Compound 2, which represents a structurally simplified congener of norbinaltorphimine 1a, was synthesized in order to evaluate the role of its second basic nitrogen in conferring kappa-opioid receptor antagonist selectivity. Congener 2 was found to be at least twice as selective as 1a as a kappa antagonist, while its N-carbobenzoxy derivative (3) was inactive at kappa receptors. This study establishes the importance of the second basic nitrogen of 1a for kappa-receptor recognition. It is proposed that this basic group mimics the guanidinium moiety of Arg7, which may be the key kappa-address component of dynorphin. PMID- 8360888 TI - Application of a conformationally restricted Phe-Leu dipeptide mimetic to the design of a combined inhibitor of angiotensin I-converting enzyme and neutral endopeptidase 24.11. PMID- 8360889 TI - Egg surface ultrastructure of eight New World phlebotomine sand fly species (Diptera: Psychodidae). AB - The ultrastructure of the egg chorionic sculpturing of eight neotropical and fly species (Lutzomyia townsendi (Ortiz, 1959), L. youngi Feliciangeli & Murillo, 1987, L. spinicrassa Osorno, Morales, Osorno, & Hoyos, 1969, L. evansi Nunez Tovar 1924, L. lichyi, Floch & Abonnenc, 1950, L. trinidadensis Newstead, 1922, L. venezuelensis Floch & Abonnenc, 1948, and L. olmeca bicolor, Fairchild & Theodor, 1971) was studied using scanning electron microscopy (SEM). A new pattern, ellipses bound by fine longitudinal ridges, was observed in L. venezuelensis. Moreover, the chorionic ultrastructure was useful for separating three isomorphic species (L. townsendi, L. youngi, and L. spinicrassa), of which L. youngi and L. spinicrassa are sympatric in some endemic foci of Tachira State, Venezuela. PMID- 8360890 TI - Hypersensitivity of horses in British Columbia to extracts of native and exotic species of Culicoides (Diptera: Ceratopogonidae). AB - Six horses from British Columbia severely affected by Culicoides hypersensitivity, a seasonal dermatitis caused by the bites of Culicoides spp., were inoculated intradermally with extracts of six species or forms of Culicoides from British Columbia, United States, and Israel. Two native and four exotic species were thought to cause the disease in their own geographical area. The horses developed large welts within 20 min after injection of any of the six extracts, indicating an immediate (type I) reaction. The skin reactions caused by each extract peaked at or after 24 h, indicating an additional delayed (type IV) reaction. These reactions confirm that the reactions to the extracts were allergic in nature. The horses were physically irritated by each extract and developed transverse ridges in the injection area similar to those seen in natural cases of the disease, again indicating an allergic reaction. Previous studies showed that control horses injected with Culicoides extract showed only a small, short-term reaction, with no delayed component, no irritation, and no transverse ridge development, further indicating that the observed reactions were allergic in nature. The affected horses reacted to all extracts of Culicoides, despite the fact that they had not been previously exposed to most of the species, indicating that the allergen(s) was present in all the extracts tested. PMID- 8360891 TI - Anopheline mosquito (Diptera: Culicidae) ecology in relation to malaria transmission in the inner and outer terai of Nepal, 1987-1989. AB - The ecology of Anopheles mosquitoes in relation to malaria transmission was studied at sprayed and unsprayed villages and two unsprayed cattle sheds in the inner terai of Sindhuli District, Central Region, and at two unsprayed villages and one cattle shed in Kanchanpur, Far Western Region of Nepal, from August 1987 to August 1989. Anopheles maculatus was the most abundant of 26 anopheline species collected in Sindhuli District; however, An. fluviatilis was collected most frequently at human bait and was infected most frequently with malaria sporozoites. Residual house spray controlled the indoor resting abundance of the endophilic resting species and protected the population from malaria during midsummer, but had less effect on exophilic resting species and those abundant after and before spray application during the fall and spring, respectively. Malaria at the unsprayed village was detected predominantly in adults of both sexes, perhaps because young children retired early and frequently slept indoors under bed nets during the early evening period of elevated anopheline host seeking activity. Malaria transmission was verified by the collection of sporozoite infected An. fluviatilis and An. maculatus during spring at cattle sheds in the forested Churia Hills and during the summer monsoon season within the unsprayed village. An. culicifacies was the most abundant of 12 anopheline species collected in Kanchanpur District. Few females of all species were collected at human bait positioned in or out of houses or had human positive blood meals; none were infected with sporozoites. Malaria incidence was higher in the study village positioned along the forest-rice field ecotone than in the cleared rice growing area. PMID- 8360892 TI - Biosynthesis of serine proteases in Lutzomyia anthophora (Diptera: Psychodidae). AB - Changes in the biosynthesis of serine proteases in adult Lutzomyia anthophora Addis were followed and compared with the larval and pupal stages. More chymotrypsinlike than trypsinlike enzyme was synthesized by 2-d-old and 3-d-old sugar-fed females and females that were fed blood 72 h earlier. A small increase in the amount of chymotrypsinlike enzyme occurred within the first 48 h after blood feeding, whereas trypsinlike enzyme activity increased rapidly after the blood meal and peaked at 72 h. [1,3-3H]DIP trypsinlike and chymotrypsinlike derivatives of sugar-fed and blood-fed females were compared using polyacrylamide gel electrophoresis. PMID- 8360893 TI - Bionomics of Anopheles quadrimaculatus and Culex erraticus (Diptera: Culicidae) in the Falls Lake basin, North Carolina: seasonal changes in abundance and gonotrophic status, and host-feeding patterns. AB - Larval and adult Anopheles quadrimaculatus Say (sensu lato) and Culex erraticus (Dyar & Knab) were collected at Falls of the Neuse Lake (Falls Lake) in North Carolina from May 1985 to December 1986. Adult mosquitoes were aspirated weekly from shelters in woodlands adjacent to larval sampling sites. An. quadrimaculatus and Cx. erraticus comprised > 95% of the total number of mosquitoes collected. An. quadrimaculatus adults exhibited vernal and autumnal peaks of abundance during both years. Cx. erraticus adults exhibited several peaks of abundance in summer and early fall of both years. An. quadrimaculatus initiated blood feeding in May and April 1985 and 1986, respectively. Only unfed females were found in late fall and winter. Cx. erraticus initiated blood feeding earlier than An. quadrimaculatus. In 1985, approximately 25% of the females in the first collection in May contained a blood meal, whereas in 1986, approximately 10% of the females in the first collection in April were blood fed. Females of both species ceased blood feeding in late fall. Larvae were sampled on a weekly basis from lake edge, flood plain, and creek edge habitats. Generally, An. quadrimaculatus larvae were most abundant in lake edge and flood plain habitats, whereas Cx. erraticus larvae were most abundant in the creek edge habitat. The population dynamics of An. quadrimaculatus were associated with seasonal changes in the level of Falls Lake. In 1985 and 1986, the level of Falls Lake gradually declined from May to mid-August until heavy rainfall caused a 1-m rise in lake level. Populations of An. quadrimaculatus larvae and adults increased significantly following the rise in the level of Falls Lake. In contrast, the abundance of larval and adult Cx. erraticus decreased with rising lake levels in late August. Water level management should be an effective method for controlling populations of An. quadrimaculatus but not for Cx. erraticus. Blood-fed mosquitoes were tested to identify bloodmeal hosts using both capillary precipitin and enzyme-linked immunosorbent assays. An. quadrimaculatus (n = 941) predominantly (99%) fed on mammals, principally white-tailed deer and horses. Cx. erraticus (n = 348) exhibited an opportunistic host-feeding pattern; blood meals were taken from mammalian (49%), reptile or amphibian (20%), and avian (31%) hosts. PMID- 8360894 TI - Life cycle of Leishmania major (Kinetoplastida: Trypanosomatidae) in the neotropical sand fly Lutzomyia longipalpis (Diptera: Psychodidae). AB - The development of Leishmania major Yakimoff & Schokhor in the New World sand fly Lutzomyia longipalpis (Lutz & Neiva) was examined by light and electron microscopy. In this unnatural host, parasites differentiated into 10 typical morphological forms, multiplied at three sites, migrated anteriorly and established in the foregut, and attached to gut surfaces. In the blood meal, amastigotes divided and transformed into two successive dividing, stumpy promastigote stages. Elongate nectomonad promastigotes developed from stumpy forms and subsequently rounded up in some flies into paramastigotes and opisthomastigotes. Differentiation into round opisthomastigotes and the apparent fusion of paramastigotes in the blood meal were novel observations in this study. Three nectomonad promastigotes--elongate, short, and metacyclic--were free swimming in the midgut lumen. Elongate nectomonad promastigotes were highly oriented in the midgut, with their flagella embedded between the epithelial microvilli. Short haptomonad promastigotes were the predominant form attached to the intima of the stomodeal valve, whereas pear-shaped haptomonad promastigotes and paramastigotes colonized surfaces of the esophagus and pharynx. Peripylarian attachment of promastigotes and paramastigotes in the pylorus, ileum, and colon was noted in 21% of flies, suggesting that suprapylarian leishmanias have not lost the ability to colonize the hindgut. L. longipalpis was a successful biological host for L. major, allowing complete development of the parasite. PMID- 8360895 TI - Antibody responses of BALB/c mice to salivary antigens of hematophagous black flies (Diptera: Simuliidae). AB - The humoral antibody responses to salivary antigens of Simulium vittatum Zetterstedt were investigated in a BALB/c mouse laboratory model. Production of antisera was stimulated by intraperitoneal immunization with salivary gland extract or by feeding flies directly on depilated mice. Antibody responses in these two groups of mice were compared by western blotting, thus characterizing "true" salivary immunogens present in salivary gland extract. Immunized mice developed IgG, IgM, and IgE antibodies which recognized several salivary gland components, ranging in molecular weight between 26 and 67 kDa. Sera from bitten mice recognized fewer antigens, indicating that some components of the salivary gland extract were poorly immunogenic or absent from the saliva secreted during blood feeding. Antisera raised against S. vittatum also were used to identify cross-reactive immunogens and allergens in salivary gland extracts from other New World simuliids (Simulium argus Williston, S. metallicum Bellardi, and S. ochraceum Walker). SDS-PAGE protein profiles indicated a high degree of similarity between salivary gland extract of S. vittatum and S. argus, and several cross-reacting antigens were identified by western blotting. In contrast, protein profiles of S. ochraceum and S. metallicum differed from the former species, both qualitatively and quantitatively. Antisera demonstrated a low degree of cross-reactivity against salivary gland extract of S. ochraceum, whereas no cross-reactivity was detected against S. metallicum. These observations were confirmed using a monoclonal antibody raised against S. vittatum salivary gland extract (designated SVSG.1.F10), which showed cross reactivity against S. argus but failed to recognize salivary gland components of either S. ochraceum or S. metallicum. PMID- 8360896 TI - Description of the immature stages of Ixodes (Pholeoixodes) baergi (Acari: Ixodidae), a parasite of cliff swallows in the United States. AB - The larva and nymph of Ixodes (Pholeoixodes) baergi Cooley & Kohls are described for the first time. This tick has been collected only in the United States on cliff swallows, Hirundo pyrrhonota, in their nests, or in adjacent habitats. To date, it has been reported from Arkansas, Colorado, Illinois, Oklahoma, and Texas. Brief notes on the synchronization of the life cycle of I. baergi with that of its host are included. PMID- 8360897 TI - Relative importance of bird species as hosts for immature Ixodes dammini (Acari: Ixodidae) in a suburban residential landscape of southern New York State. AB - Abundance of birds and their tick parasites were estimated in a residential community located in Westchester County, NY, where Lyme disease is endemic. In total, 36 bird species (416 captures) were collected, of which 25 species (69%) were parasitized by ticks. Ixodes dammini Spielman, Clifford, Piesman & Corwin composed 96.4% of the 1,067 ticks found on birds. The bird species most heavily parasitized was house wren, Troglodytes aedon Vieillot (11.1 Ixodes dammini per bird). Relative density estimates of birds, using fixed circle radius counts, revealed dominance by the American robin, Turdus migratorius L. (29.3%), followed by the common grackle, Quiscalus quiscula (L.) (9.3%). Bird density estimates were combined with tick abundance data to calculate an importance value for each bird species as a host for immature I. dammini. The American robin was most important, accounting for 72.7% of all larval I dammini found on birds, followed by the common grackle (8.2%) and the house wren (5.9%). Both the American robin and house wren are reservoir competent for the Lyme disease spirochete Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner and therefore may contribute to the risk of Lyme disease for humans. During August when larvae were most prevalent, 39% of the American robins and 70% of the common grackles were observed on lawns. These species are probable contributors to nymphal I. dammini populations found on lawns. PMID- 8360898 TI - Removal of attached nymphs and adults of Ixodes ricinus (Acari: Ixodidae). AB - Chemical and mechanical methods of removing Ixodes ricinus (L.) attached to the skin of pigs and sheep were tested experimentally. Three frequently advocated chemical treatments (gasoline, fingernail polish, and methylated spirit) failed to induce self-detachment of the ticks within 30 min. Also, the success of the subsequent mechanical removal was not influenced by chemical treatment. Two methods of mechanical removal of the ticks also were compared: (1) pulling straight out with a blunt forceps and (2) rotation of the tick around its body axis, using a "Tick Solution" forceps (Instruments of Sweden, Stamford, CT). Pulling frequently resulted in the complete removal of the tick, but fragments of the mouthparts that remained in the skin were often quite large. In contrast, if the tick was removed by rotation without pulling, the tip of the hypostome usually broke off and remained in the skin, but this portion was generally quite small. PMID- 8360899 TI - Replacement times, storage, and vertebrate host source of blood for in vitro feeding of Haematobia irritans (Diptera: Muscidae) adults. AB - Studies were conducted to determine optimum replacement intervals, storage times, and vertebrate source of blood used to feed Haematobia irritans (L.) adults in vitro. Feeding success was measured by the total number of larvae produced per female during 10-d experimental periods which combined adult female survival, egg production, and egg hatch. The number of larvae per female was reduced significantly when blood replacement intervals were increased from 24 to 48 h; however, blood replacement intervals could be increased to 48 h without affecting larval production if the blood was agitated continuously. Maximum larval production was obtained when adult flies fed on whole, citrated bovine blood that had been stored at 3 degrees C for 2 wk; however, there was no difference in the number of larvae produced per female when adults were fed blood stored at -20 degrees C for 2-52 wk. Significantly more larvae were produced when adults fed on citrated porcine blood than bovine or ovine blood. PMID- 8360900 TI - Spatial and temporal patterns of Ixodes scapularis (Acari: Ixodidae) in southeastern Connecticut. AB - The spatial distribution and abundance of host-seeking Ixodes scapularis Say (formerly I. dammini) were studied in 10 residential sites in woodlands during 1989-1991. In total, 7,385 larval, 2,202 nymphal, 164 female, and 248 male I. scapularis were collected in Old Lyme, Lyme, East Haddam, and Chester, CT. The majority of host-seeking I. scapularis larvae (84.2%) and nymphs (73.5%) were collected within the woodland plots, whereas a large proportion of the adults were recovered from lawn (36.4%) and transitional areas between lawns and forest (20.9%). The majority (71.1% of 1,244) of all stages of I. scapularis on the lawn were recovered within 1 m of the lawn edge, particularly along woods and stone walls. In contrast, most of the I. scapularis (60.0% of 3,065) collected in the woods were > 3 m from any defined edge and ticks were recovered throughout the forested plots. The abundance of nymphs on the lawns (1.0-29.4 nymphs per ha per sample) and in the woods (17.3-271.5 nymphs per ha per sample) varied significantly among the 10 residences during June and July. The average rate of infection by Borrelia burgdorferi, the causal agent of Lyme disease, in the nymphs was 14.2, 14.1, and 15.5% for 1989, 1990, and 1991, respectively. The abundance of I. scapularis nymphs in the forest was significantly higher in June 1991, than in 1989 or 1990. The risk of exposure to infected nymphs of I. scapularis varied spatially with the landscape and individual residence, and temporally. PMID- 8360901 TI - Mutation in the pla gene of Yersinia pestis alters the course of the plague bacillus-flea (Siphonaptera: Ceratophyllidae) interaction. AB - Yersinia pestis possesses a unique gene (pla) encoding coagulase and fibrinolysin which is implicated in the transmission of plague by fleas. This gene is encoded on the highly conserved but poorly characterized 'pesticin' plasmid pKYP1. The role of the pKYP1-encoded gene, pla, in plague transmission was addressed by feeding fleas on blood containing avirulent Y. pestis strain EV76-6 and three derivatives of this strain (K10-2, K10-3, and K10-5) carrying Tn801 insertions in pKYP1. One of these mutant strains, K10-5, contains an insertion within the pla gene that eliminates both coagulase and fibrinolysin activities, whereas strains K10-3 and K10-2 retain both pla-associated phenotypes. After feeding, it was found that flea mortality at 4 d after infection associated with strain K10-5 (26%) was significantly lower than the mortality observed with other strains (53 64%). These results suggest that expression of the pla gene product may contribute to the deleterious effects of plague bacilli on fleas that have been associated with flea blockage and plague transmission. This increased mortality is not caused simply by an increased bacterial load in fleas containing pla+ bacteria because fleas ingesting pla+ strains contained no more bacteria by flea blot hybridization analysis than did those that ingested the pla- strain K10-5. It is anticipated that further work in this area will clarify the mechanism by which pla acts and will reveal additional genetic loci in the plague bacillus which are required for transmission by fleas. PMID- 8360902 TI - Detection of Anaplasma marginale (Rickettsiales: Anaplasmataceae) in hemolymph of Dermacentor andersoni (Acari: Ixodidae) with the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to detect Anaplasma marginale in hemolymph collected from live Dermacentor andersoni Stiles ticks. Hemolymph was collected from severed legs of male and female ticks exposed to A. marginale as either nymphs or adults. Heat treatment was found to be the optimum method of hemolymph preparation for PCR. Hemolymph samples were collected and pooled from adult ticks exposed as nymphs on days 0-10 of feeding on a susceptible calf. For male and female ticks exposed as adults, samples were collected as ticks fed 7 d on an infected calf, while being held 9 d between feedings, and during a second feeding of 10 d (or to repletion) when they transmitted the parasite. Hemolymph samples were collected from uninfected ticks at the same times to serve as controls. Anaplasma marginale DNA was amplified with primers BAP-2 (5' GTATGGCACGTAGTCTTGGGATCA-3') and AL34S (5'-CAGCAGCAGCAAGACCTTCA-3'), which flank a 409-bp fragment of the A. marginale Florida isolate msp1 beta gene. Infected tick hemolymph was PCR-positive for A. marginale at all collection times, including unfed adults infected as nymphs and previously unexposed adults that fed on infected calves for only 1 d. The PCR-based assay of tick hemolymph proved to be a sensitive method for identification of infected ticks, potentially without killing them; it would be well suited for identification of laboratory- or field-infected ticks that could then be used for further studies. The primers used in this assay were also found specific when tested with species of 18 different genera, and universal for 7 A. marginale isolates from diverse geographical areas of the United States. PMID- 8360903 TI - Detection of Anaplasma marginale (Rickettsiales: Anaplasmataceae) in secretagogue induced oral secretions of Dermacentor andersoni (Acari: Ixodidae) with the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to detect Anaplasma marginale in secretagogue-induced oral secretions of male and female Dermacentor andersoni Stiles exposed as nymphs or adults by feeding on infected calves. A 409-bp DNA fragment derived from the A. marginale (Florida isolate) msp1 beta gene was amplified with oligonucleotide primers BAP-2 (5'-GTATGGCACGTAGTCTTGGGATCA-3') and AL34S (5'-CAGCAGCAGCAAGACCTTCA-3'). The target DNA was amplified in oral secretions of female ticks exposed to A. marginale as adults and stimulated to secrete by injection of dopamine. Conversely, A. marginale was detected in saliva from prefed female ticks exposed as nymphs only after stimulation with a combination of dopamine, gamma-aminobutyric acid, pilocarpine, and theophylline. Saliva from ticks exposed as nymphs and stimulated with ergot alkaloids did not contain the A. marginale target DNA. Saliva collected after 11 d of feeding from dopamine-stimulated male ticks contained A. marginale DNA. The results indicate that A. marginale is present in tick saliva and suggest that the parasite can be transmitted to cattle via saliva of feeding ixodid ticks. The variable appearance of A. marginale in saliva, regardless of the method used to induce salivation, suggests that transmission of A. marginale may be affected by the physiological state of the tick. PMID- 8360904 TI - Extension of the range of Dermacentor variabilis (Acari: Ixodidae) in Pennsylvania. AB - The American dog tick, Dermacentor variabilis (Say), until recently was recorded only from the southeastern and southwestern counties of Pennsylvania. Since 1968, this species has expanded its range and is reported from 63 of Pennsylvania's 67 counties. This range extension is a matter of concern to the medical community and to physicians throughout Pennsylvania, particularly those with practices in areas where this tick was previously unknown and who may not be familiar with the symptoms of Rocky Mountain spotted fever. PMID- 8360905 TI - Association of ticks (Acari: Ixodoidea) with rodent burrows in northern Senegal. AB - Four species of ticks were retrieved from burrows of 64 multimammate rats, Mastomys erythroleucus (Temminck), 55-gerbils, Taterillus gracilis (Thomas) or T. pygargus (Cuvier), 13 Nile rats, Arvicanthis niloticus (DeMarest), and five Geoffroy's ground squirrels, Xerus erythropus (Geoffroy) from May 1987 through August 1988 at two study sites in northern Senegal. Ornithodoros sonrai Sautet & Witkowski were recovered from 95% (74/78) of burrows near Bandia and 6% (4/66) of burrows near Yonofere. Eight Hyalomma truncatum Koch, four Rhipicephalus guilhoni Morel & Vassiliades, and one R. sulcatus Neumann were recovered from 144 rodent burrows (nine tick-positive burrows) from both locations. No seasonal trend of tick abundance or activity was noted, nor was any pattern of burrow preference by ticks detected. Rodent burrows in either location appeared to be little used by ixodid ticks. PMID- 8360906 TI - Habitat overflow, a source of larval mortality for Aedes sierrensis (Diptera: Culicidae). AB - In laboratory and field tests, larvae of the western tree hole mosquito, Aedes sierrensis (Ludlow), were flushed by rainfall from both glass containers and natural tree holes. After 7 d and an accumulated rainfall of 7.9 cm (3.1 in), between 0 and 327 Ae. sierrensis immatures were recovered in collection devices placed below four natural tree holes. Habitat overflow affected all larval stages and may be an important, but overlooked, density-independent source of larval mortality for mosquitoes developing in some water-filled containers. PMID- 8360907 TI - Assimilation rates of different particulate foods for Simulium verecundum (Diptera: Simuliidae). AB - Particulate food assimilation rates for larvae of Simulium verecundum Stone & Jamnback were studied using three radiolabelled particulate foods: Navicula pelliculosa Breb. ex Kutz.) Hilse (a diatom), Scenedesmus quadricauda (Turp.) Breb. (a green alga), and field-collected, size-fractionated (< 3.0 microns) heterotrophic bacterioplankton. Assimilation was determined by radiolabelling the microorganisms followed by a 5-h laboratory feeding of each food to fifth- to seventh-instar S. verecundum. The bacterioplankton provided the highest assimilation efficiency (27.8%). N. pelliculosa produced higher assimilation efficiency estimates (19.5%) than did S. quadricauda (4.0%). The relationship between black fly abundance and the availability of quickly assimilated food is discussed. PMID- 8360908 TI - Influence of low temperature (-30 degrees C) on the different stages of the human allergy mite Dermatophagoides pteronyssinus (Acari: Epidermoptidae). AB - Effects of low temperature (-30 degrees C) on the different life stages of Dermatophagoides pteronyssinus (Trouessart) were studied. Humid cold air at -30 degrees C killed all stages of mites except eggs after 10 min; after 35 min exposure, 20% of the eggs hatched after the incubation period. Dry, cold air at 30 degrees C killed 40% of all stages of mites except eggs after 4 min and 100% after 5 min; all eggs died after 1 min exposure. PMID- 8360909 TI - Seasonal variation in the capacity of the bank vole to infect larval ticks (Acari: Ixodidae) with the Lyme disease spirochete, Borrelia burgdorferi. AB - Seasonal variation in the capacity of bank voles, Clethrionomys glareolus (Schreber), to infect larval Ixodes ricinus (L.) ticks with Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner was examined from May through October 1991 at Bogesund, near Stockholm in south-central Sweden. Although larval infestations of bank voles were greatest in June and July, nearly 70% of all larval ticks infected with spirochetes by bank voles at this site became infected during August and September. Seasonality of infectivity was related to the degree of earlier nymphal infestation on voles as well as to the age composition of the vole population. These factors may influence the infectivity of other rodent reservoirs of B. burgdorferi, both in Europe and North America. Moreover, in determining the reservoir potential of tick hosts, a host population's spirochetal infectivity should be determined for the entire period of larval infestation rather than just during the period of peak larval infestation. PMID- 8360910 TI - Adult emergence patterns in Musca autumnalis (Diptera: Muscidae). AB - Adult emergence patterns were investigated in four lines of face flies, Musca autumnalis De Geer, in a 16:8 (L:D) h photoperiod and corresponding 30:25 degrees C thermo-period. Most emergence occurred in a specific time interval ("emergence gate") that began at 2000 hours and continued until 1200 hours. A cohort of puparia completed emergence in two or three consecutive emergence gates. The four lines showed different median times and rates of emergence. Laboratory rearing seemed to select progeny of earlier median times and faster rates of emergence. F1 progeny of the two lines showed patterns of emergence intermediate between those of the parents. Female flies tended to eclose earlier than males in all lines. PMID- 8360911 TI - Egg yolk and bacteria growth medium for Musca domestica (Diptera: Muscidae). AB - Six preparations of egg yolk media inoculated with Escherichia coli (Migula) were evaluated as an in vitro growth system for immature house flies, Musca domestica L. Larval development, based on pupation and eclosion success, was normal on all media supplemented with E. coli, but few larvae survived without bacteria (4%). Pupation (72%) and eclosion (63%) were significantly higher on egg yolk media without mannitol than on media with mannitol or on blood agar controls. PMID- 8360912 TI - Ecological studies of Ixodes scapularis (Acari: Ixodidae) in central Mississippi: lateral movement of adult ticks. AB - Lateral movement by adult Ixodes scapularis Say was measured by two mark-release recapture studies in which ticks were collected by flagging, marked with tiny drops of model paint, released at predetermined spots within the study site, and subsequently recaptured during weekly sampling by flagging. In the first mark release-recapture experiment, 10/23 ticks were recaptured; all but 3 (2 collected at 3 m and 1 at 1 m) were collected at the release point. In the second experiment, 43/82 ticks were recaptured and all but 1 (which was collected 1 m from the release point) were collected within 0.5 m of their release point. Results of this study indicate that lateral movement by questing adult I. scapularis is minimal. PMID- 8360913 TI - Can flies stand in for humans? PMID- 8360914 TI - Methylated cytosine at Dcm (CCATGG) sites in Escherichia coli: possible function and evolutionary implications. AB - The frequency and distribution of methylated cytosine (5-MeC) at CCATGG (Dcm sites) in 49 E. coli DNA loci (207,530 bp) were determined. Principal observations of this analysis were: (1) Dcm frequency was higher than expected from random occurrence but lower than calculated with Markov chain analysis; (2) CCTGG sites were found more frequently in coding than in noncoding regions, while the opposite was true for CCAGG sites; (3) Dcm site distribution does not exhibit any identifiably regular pattern on the chromosome; (4) Dcm sites at oriC are probably not important for accurate initiation of DNA replication; (5) 5-MeC in codons was more frequently found in first than in second and third positions; (6) there are probably few genes in which the mutation rate is determined mainly by DNA methylation. It is proposed that the function of Dcm methylase is to protect chromosomal DNA from restriction-enzyme EcoRII. The Dcm methylation contribution to determine frequency of oligonucleotides, mutation rate, and recombination level, and thus evolution of the E. coli genome, could be interpreted as a consequence of the acquisition of this methylation. PMID- 8360915 TI - The higher fungus Protomyces inouyei has two group I introns in the 18S rRNA gene. AB - The nucleotide sequence of the small-subunit rRNA (18S rRNA) coding gene in the higher fungus Protomyces inouyei contains two group I introns. This is the first report of two group I introns in the 18S rRNA coding region. Based on the comparison of the two introns of Protomyces inouyei with those of the green alga Ankistrodesmus stipitatus, and the other two higher fungi Pneumocystis carinii and Ustilago maydis, the Protomyces introns are group I introns containing the highly conserved sequence elements P, Q, R, and S. Intron A of Protomyces inouyei is located in the same position as in Pneumocystis carinii while intron B shares the location with that in Ustilago maydis. The phylogenetic relationships strongly support horizontal transfer of these group I introns. PMID- 8360916 TI - Sequences related to the ox pancreatic ribonuclease coding region in the genomic DNA of mammalian species. AB - Mammalian pancreatic ribonucleases form a family of homologous proteins that has been extensively investigated. The primary structures of these enzymes were used to derive phylogenetic trees. These analyses indicate that the presence of three strictly homologous enzymes in the bovine species (the pancreatic, seminal, and cerebral ribonucleases) is due to gene duplication events which occurred during the evolution of ancestral ruminants. In this paper we present evidence that confirms this finding and that suggests an overall structural conservation of the putative ribonuclease genes in ruminant species. We could also demonstrate that the sequences related to ox ribonuclease coding regions present in genomic DNA of the giraffe species are the orthologues of the bovine genes encoding the three ribonucleases mentioned above. PMID- 8360917 TI - Transcribed heteroplasmic repeated sequences in the porcine mitochondrial DNA D loop region. AB - The mitochondrial D-loop region of the pig, Sus scrofa, was found to be several hundred base pairs larger than the corresponding region in cow, a related artiodactyl species, primarily because of an insertion containing the tandemly repeated sequence CGTGCGTACA. Porcine mitochondrial DNA from the tissue of a single animal exhibits a large population of length polymorphs, each member of which may have as few as 14 or as many as 29 of these repeat units. This intracellular variability may be due to the repeated and self-complementary properties of this sequence, which would favor mispairing and lead to replication slippage. The repeat domain is unusual in that symmetry properties suggest it may assume alternative conformations including cruciforms and left-handed (Z) DNA. It also appears to be the longest known, naturally occurring, alternating purine pyrimidine sequence. In order to understand the functional significance of this heteroplasmic domain that potentially disrupts a key regulatory region in the mitochondrial genome, RNA and DNA mapping studies were conducted which located this region between the H-strand replication origin and the putative L-strand transcriptional start site. H-strand RNA analysis demonstrated that this heteroplasmic region is transcribed and, therefore, that priming for H-strand DNA replication in mitochondria is independent of the primer RNA length or secondary structure. PMID- 8360918 TI - Heterogeneity in the concerted evolution process of a tandem satellite array in meadow mice (Microtus). AB - The evolutionary history of a 160-bp tandem satellite array, originally described from Microtus chrotorrhinus and called MSAT-160, was examined in related species of arvicolid rodents by sequence analyses, quantitative dot blotting, and Southern blotting. Results indicate that MSAT-160 is present in 12 of the 20 species and subspecies of Microtus assayed, but not in species belonging to any of the eight other genera examined. DNA from each species containing MSAT-160 was digested with 12 restriction endonucleases and restriction patterns were obtained reflecting the variable extent of homogenization of any given variant in different species. For example, with MboI digestion, M. chrotorrhinus produced a type A ladder pattern where most monomers contain the restriction site, M. ochrogaster generated a type B pattern where most monomers lack the site, and M. agrestis yielded a pattern intermediate between the A and B types. Further, dot blotting revealed copy-number differences between species. These findings indicate that changes in the periodic structure and amount of satellite DNA have occurred since these species last shared a common ancestor. In addition, various species-specific patterns were documented, illustrating that mechanisms other than genome-wide homogenization, such as stochastic mutation, out-of-register crossing over, deletion, and random amplification also play a role in structuring tandem arrays. Stochastic mutation and homogenization rates in satellite DNA, levels of species diversity, and magnitudes of chromosomal divergence differ significantly in Microtus, Mus and Ctenomys, the three rodent lineages examined. PMID- 8360919 TI - Origin of glutaminyl-tRNA synthetase: an example of palimpsest? AB - Sequence data and evolutionary arguments suggest that a similarity may exist between the C-terminal end of glutaminyl-tRNA synthetase (GlnRS) and the catalytic domain of glutamine amidotransferases (GATs). If true, this would seem to imply that the amidation reaction of the Glut-tRNA(Gln) complex was the evolutionary precursor of the direct tRNA(Gln) aminoacylation pathway. Since the C-terminal end of GlnRS does not now have an important functional role, it can be concluded that this sequence contains vestiges that lead us to believe that it represents a palimpsest. This sequence still conserves the remains of the evolutionary transition: amidation reaction-->aminoacylation reaction. This may be important in deciding which mechanism gave origin to the genetic code organization. These observations, together with results obtained by Gatti and Tzagoloff [J. Mol. Biol. (1991) 218:557-568], lead to the hypothesis that the class I aminoacyl-tRNA synthetases (ARSs) may be homologous to the GATs of the trpG subfamily, while the class II ARSs may be homologous to the GATs of the purF subfamily. Overall, this seems to point to the existence of an intimate evolutionary link between the proteins involved in the primitive metabolism and aminoacyl-tRNA synthetases. PMID- 8360920 TI - Close phylogenetic relationship between Vestimentifera (tube worms) and Annelida revealed by the amino acid sequence of elongation factor-1 alpha. AB - To clarify the phylogenetic position of Vestimentifera (tube worms), 346-bp fragments of the elongation factor-1 alpha (EF-1 alpha) gene (939-1286 according to the numbering of the human gene) of a vestimentiferan, Lamellibrachia sp., a sternaspid polychaete, Sternaspis scutata, an earthworm, Pheretima sp., and a gastropod, Alviniconcha hessleri, were sequenced. From the amino acid sequences of these EF-1 alpha, and those of two other vertebrates and two arthropods, phylogenetic relationships were deduced by the maximum likelihood (ML) method, by which the phylogenetic tree can be inferred without assuming constancy of the molecular evolutionary rate. For the ML tree and all of seven alternative trees, whose log-likelihoods could not be discriminated from that of the ML tree by the criterion of the standard error, the vestimentiferan, the polychaete, and the oligochaete formed a clade, excluding the arthropods and the gastropod as outgroups. This result is convincing evidence that Vestimentifera are protostomes that are closely related to Annelida. The ML tree suggests that Vestimentifera are more closely related to Polychaeta than to Oligochaeta, though the data were not sufficient to discriminate these three groups at a significant level. From recent evidence such as morphological characteristics and molecular information, it may safely be said that vestimentiferans should be included in the Annelida provided this phylum contains polychaetes and oligochaetes. PMID- 8360921 TI - Molecular evolutionary analysis based on the amino acid sequence of catalase. AB - Heme-containing catalase sequences from 20 different organisms representing prokaryotes, fungi, animals, and plants have been compiled for phylogenetic reconstruction. Phylogenies based on distance and parsimony analysis show that fungal and animal catalases can be derived from one ancestor, whereas bacterial catalases fail to form a monophyletic group. Plant catalases appear to form a second class of catalases that arose independently from a possible prokaryotic ancestor. PMID- 8360922 TI - Man's place in Hominoidea revealed by mitochondrial DNA genealogy. PMID- 8360923 TI - Clinical chemoprevention: developing a cancer prevention strategy. PMID- 8360924 TI - Dietary supplements reduce cancer deaths in China. PMID- 8360925 TI - European tamoxifen studies moving ahead. PMID- 8360926 TI - NCI expert panel issues summary report on excise tax on cigarettes. PMID- 8360927 TI - Regulatory approval and technological advances raise hopes for photodynamic therapy. PMID- 8360928 TI - Man's best friend may be companion in cancer research. PMID- 8360929 TI - Efficacy and cost-effectiveness of cancer treatment: rational allocation of resources based on decision analysis. PMID- 8360930 TI - Natural killer cells and bone marrow transplantation. AB - Bone marrow transplantation is currently used in the treatment of a variety of neoplastic and nonneoplastic diseases. However, significant obstacles still limit the efficacy of this procedure. These include the occurrence of graft-versus-host disease, the failure of the marrow to engraft, the susceptibility of patients to opportunistic infections during the period of immunodeficiency after transplantation before full recovery of immune function, and finally, the recurrence of the cancer. Natural killer (NK) cells are lymphoid cells responsible for mediating a variety of immunologic and homeostatic functions. Initially described almost 20 years ago, the full range of functions carried out by these enigmatic cells continues to unfold. NK cells may be both beneficial and deleterious in bone marrow transplantation, depending on their genotype and activation status. Resting host-derived NK cells appear capable of mediating resistance to both autologous and allogeneic bone marrow cell grafts. At the other end of the spectrum, the transfer of activated NK cells of donor type appears to produce multiple beneficial effects during both syngeneic and allogeneic bone marrow transplantation. Here, we review and attempt to reconcile the literature concerning the basic biology of NK cells and their effects on hematopoiesis, both in vitro and in vivo. We also discuss the current issues in bone marrow transplantation and the potential role NK cells may play in determining the outcome of the marrow graft, the occurrence of graft-versus-host disease, and the generation of a graft-versus-tumor response when bone marrow transplantation is used for the treatment of cancer. PMID- 8360932 TI - Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. AB - BACKGROUND: A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia. PURPOSE: To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian. METHODS: Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years. RESULTS: A total of 324 deaths occurred during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P > .10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P > .10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P > .10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P > .10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups. CONCLUSIONS: No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus. IMPLICATIONS: Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia. PMID- 8360931 TI - Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. AB - BACKGROUND: Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients. PURPOSE: We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian. METHODS: Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances. RESULTS: A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality. CONCLUSIONS: The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population. IMPLICATIONS: The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements. PMID- 8360933 TI - Radiopharmaceutical therapy of 5T33 murine myeloma by sequential treatment with samarium-153 ethylenediaminetetramethylene phosphonate, melphalan, and bone marrow transplantation. AB - BACKGROUND: Total-body irradiation, followed by hematopoietic system rescue by bone marrow transplantation (BMT), has been found to improve the response of patients with multiple myeloma to treatment with melphalan. The problems of nonhematopoietic toxicity from whole-body irradiation might be circumvented by using a bone-seeking radiopharmaceutical, such as samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP), to ablate the bone marrow. PURPOSE: A mouse model system for multiple myeloma was used to evaluate the potential therapeutic efficacy of sequential therapy with 153Sm-EDTMP, melphalan, and BMT. METHODS: Female C57BL/KaLwRij mice were inoculated with 8 x 10(5) 5T33 murine myeloma cells. Treatment protocols were begun 3 or 10 days later, when the myeloma was either confined to bone marrow or disseminated in liver, spleen, and lymph nodes, simulating human multiple myeloma. 153Sm, a potent beta particle-emitting radioisotope of short half-life (46.7 hours), was linked to the bone-seeking chelate EDTMP. Animals in the first treatment group were each given 22.5 MBq 153Sm-EDTMP via the jugular vein (day 3 or 10), followed by 18.5 mg/kg melphalan (maximum tolerated dose) given intraperitoneally 5 days later (day 8 or 15) and syngeneic BMT another 2 days later (day 10 or 17). Survival in groups of six to 10 animals for each time series was compared with that in mice left untreated (control cohort), in mice treated with 153Sm-EDTMP alone (day 3 or 10), or in mice treated with melphalan alone (day 8 or 15). The hematopoietic systems of animals in the latter two treatment groups recovered full function, obviating the necessity of BMT. The end point was onset of paraparesis, at which time the animals were immediately killed by carbon dioxide asphyxiation. RESULTS: Median survival in untreated control animals was 23 days in those with localized disease and 24 days in those with disseminated myeloma. Treatment with 153Sm-EDTMP alone improved survival to a median of 29 days when commenced on day 3 and 30 days when begun on day 10. Melphalan treatment alone improved the median survival to 31 days for animals with localized myeloma and 34 days in animals with disseminated disease. Additional improvement in survival to a median of 42 days was achieved in animals treated 3 days after tumor inoculation with sequential 153Sm-EDTMP, melphalan, and BMT; median survival was 40 days using this regimen in animals with disseminated myeloma. CONCLUSIONS: Animals in all three treatment protocols survived longer than those left untreated after inoculation with myeloma cells (P < .001). Sequential treatment with 153Sm-EDTMP, melphalan, and BMT was significantly more effective than single agent treatment (P < .01). No evidence of radiotoxicity was detected in nonhematopoietic organs. IMPLICATIONS: The survival advantage conferred by our sequential treatment protocol suggests its potential clinical usefulness in the treatment of multiple myeloma and other hematologic malignancies in humans. PMID- 8360934 TI - Spectrum of mutation and frequency of allelic deletion of the p53 gene in ovarian cancer. AB - BACKGROUND: The p53 gene encodes a nuclear phosphoprotein present in low levels in normal human cells. The wild-type form of this protein functions to restrain inappropriate cellular proliferation. Approximately one half of human epithelial ovarian cancers have mutations in the p53 gene and overexpress the mutant protein product. Deletion of one allele of the p53 gene also frequently occurs in these cancers. PURPOSE: We sought to define the spectrum of mutations in the p53 gene in epithelial ovarian cancer with respect to both the specific codons involved and the type of mutations observed. We also examined the frequency of allelic deletion of the p53 gene in cancers containing p53 gene mutations. METHODS: Tissue samples from the epithelial ovarian cancers of 62 patients were obtained during initial laparotomy. Histologic examination was done to ensure that the experimental samples used in this study contained more than 75% cancer cells. Total RNA was extracted from these samples and separately from matched control noncancerous regions of the surgical specimen or white blood cells. The purified RNAs were reverse transcribed to generate cDNA copies of exons 4-10 of the p53 gene. Two rounds of polymerase chain reaction (PCR) were conducted to produce enough template for DNA sequence analysis of the regions of interest within the p53 gene. Dideoxy sequencing of at least two independent productions of each amplified DNA template was done to confirm the validity of the mutations found. Allelic deletions were identified by PCR and gel electrophoretic techniques to examine three polymorphisms within the p53 gene in cancer-normal DNA pairs. RESULTS: We identified 45 mutations in exons 5-8 of the p53 gene, where mutations frequently have been found in other cancer types. An additional mutation was identified in exon 4. Overall, 72% of the mutations were transitions, 24% transversions, and 4% microdeletions. Allelic deletion of the other p53 allele was seen in 67% of ovarian cancers in which a p53 mutation was present. Germ-line p53 mutations were not found in any patients whose cancers had p53 mutations. CONCLUSIONS AND IMPLICATIONS: Like p53 mutations in other types of human cancers, those in epithelial ovarian cancers are diverse and occur frequently in exons 5 8. The predominance of transition mutations suggests that p53 mutations in ovarian cancer arise because of spontaneous errors in DNA synthesis and repair rather than the direct interaction of carcinogens with DNA. These molecular data are consistent with data from epidemiologic studies that have failed to demonstrate a convincing relationship between exposure to environmental carcinogens and the development of ovarian cancer. PMID- 8360935 TI - Suramin toxicity and efficacy in agnogenic myeloid metaplasia. PMID- 8360936 TI - Re: Oral cavity cancer in non-users of tobacco. PMID- 8360937 TI - Re: Oral contraceptives and breast cancer. PMID- 8360938 TI - Exposure of rats to hyperoxia: alteration of lavagate parameters and macrophage function. AB - Exposure of rats to hyperoxia (100% oxygen for 64 h) resulted in striking alterations in the properties of samples obtained by bronchoalveolar lavage. The yield of neutrophils, lymphocytes, and red blood cells was increased, while the number of harvested alveolar macrophages decreased. The acellular lavage fluid level of protein was elevated, indicating lung damage. However, acellular phospholipid levels were unchanged. The ability of alveolar macrophages to produce reactive forms of oxygen in response to zymosan was significantly decreased by oxygen exposure. This impaired function was not fully explained by a decrease in viability of these phagocytes. In contrast, stimulant-induced chemiluminescence was elevated after hyperoxia. This rise was not due to a change in cellular antioxidant levels or to a discernible increase in arachidonic acid metabolites. However, it was associated with increased cellular lipid peroxidation. PMID- 8360939 TI - Role of purified IgG1 in pulmonary hypersensitivity responses of the guinea pig. AB - Guinea pigs have been used extensively to model pulmonary hypersensitivity responses. Although guinea pigs produce mainly immunoglobulin G1 (IgG1) antibodies and humans produce IgE, both immunoglobulin classes have been shown to be regulated similarly. We used an established guinea pig model to examine the role of IgG1 in immediate- and late-onset pulmonary hypersensitivity responses. IgG1 was purified from the serum of ovalbumin-immunized animals and shown to be free of IgE. It was transferred into naive recipients in doses quantified on the basis of its biological activity as measured in the passive cutaneous anaphylaxis (PCA) assay. Inhalation challenge of recipient animals 24 h later with an ovalbumin aerosol produced immediate-onset airway constrictive responses, with response dependent upon the quantity of antibody passively administered. None of the recipient animals displayed a late-phase response previously shown to be characterized by increased breathing frequency, airflow limitation during exhalation, and mild fever. However, pulmonary eosinophilia, measured at 24 h postinhalation challenge, was detected with the severity of the eosinophilia dependent upon the quantity of IgG1 administered. The results indicated that immediate-, but not late-onset, responses were associated with IgG1 antibody. Occurrence of late-onset pulmonary eosinophilia indicated that eosinophilic inflammation, a recognized characteristic of hypersensitivity responses, was related to antigen-specific IgG1 antibody. PMID- 8360940 TI - Groundwater pesticides: interactive effects of low concentrations of carbamates aldicarb and methomyl and the triazine metribuzin on thyroxine and somatotropin levels in white rats. AB - Using full-factorial design experiments for three variables at two levels each and center replicates, we examined the effects of common agricultural carbamate insecticides, aldicarb and methomyl, and a triazine herbicide, metribuzin, on hormone levels in Sprague-Dawley rats. Fifty-four female rats were sampled at 2 and 6 wk during a 6-wk exposure to individual chemicals or to combinations of them. Some main effects and interaction effects were significant. For example, rats treated with the herbicide (metribuzin) were hyperthyroid. The interactions of all three chemicals also significantly increased thyroxine levels. One year later, we repeated these experiments for 16 wk using 54 male rats; the results were very similar. Metribuzin alone significantly increased thyroxine throughout the second study (at 7, 13, and 16 wk). Somatotropin levels were significantly altered after 13 wk of exposure. The same concentrations and mixtures of these three pesticides have now been shown to be implicated in learning impairment and other neurological functions, immune parameter changes, and endocrine changes. These findings support the concept of the interconnectedness of the nervous, endocrine, and immune systems and raise the likelihood of impacts on all three systems if one is shown to be affected. Development, growth, and reproduction all depend on the proper function of these three systems. These results strongly suggest the need to reassess currently allowed "safe" levels of chemicals based on adult dosages that are accepted in ground-water and in our food supplies. PMID- 8360941 TI - Correlation between tissue and plasma concentrations of oxytetracycline in veal calves. AB - Mercer et al. (1977) proposed a three-phase experimental design to establish withdrawal times, based on plasma pharmacokinetics. This approach was the premise of a study in which plasma pharmacokinetics and tissue depletion data of oxytetracycline after intramuscular administration were correlated. Correlations between estimated and measured concentrations were shown to be significant for kidney tissue (r = .9236, p < .001), liver tissue (r = .9302, p < .01) as well as for muscle tissue (r = .9045, p < .001). The data presented support the pharmacokinetic approach as proposed by Mercer et al. (1977) and demonstrate that tissue elimination rates correlate highly with elimination rates in plasma. Although generalizations must be applied with caution, this article shows that when certain criteria are fulfilled, plasma pharmacokinetics can reliably predict tissue withdrawal times. PMID- 8360942 TI - Porphyrin profiles in the nestling European starling (Sturnus vulgaris): a potential biomarker of field contaminant exposure. AB - Porphyrin patterns in avian and mammalian tissues and/or excreta have been proposed as qualitative and quantitative biomarkers of exposure to polyhalogenated hydrocarbons, heavy metals, and other environmental contaminants. However, no widely distributed terrestrial species has been characterized as a suitable model in which to assess porphyrin profiles in the evaluation of environmental contaminant exposure. The European starling, whose nests can be readily established and manipulated on contaminated sites, has many qualities that accommodate controlled field research and that suggest its suitability for such assessments. In the present studies, we measured the total and individual porphyrin concentrations in liver, kidney, and fecal-urate excreta of nestling starlings from a noncontaminated field site from day of hatch through d 17 of the nestling period. Total as well as individual 8-, 7-, 6-, 5-, 4-, and 2-carboxyl porphyrin concentrations in liver, kidney, and fecal-urate excreta were readily detectable by high-performance liquid chromatography (HPLC) spectrofluorometric techniques and displayed tissue-specific patterns throughout the developmental period. Liver and fecal-urate porphyrin patterns were established by d 4 subsequent to hatch and remained constant through d 17 of development, whereas renal porphyrin profiles were constant throughout the entire developmental period. In controlled field studies, nestling starlings were treated with either HgCl2 or hexachlorobenzene (HCB), and tissue and excreta porphyrins were extracted and evaluated. The findings suggest that the nestling starling may serve as a suitable model species in which to monitor the effects of field contaminant exposure to wildlife based on chemical-induced changes in tissue or excreta porphyrin levels. PMID- 8360943 TI - Comparative cytotoxic responses of cultured avian and rodent aortic smooth muscle cells to allylamine. AB - The present studies were designed to compare the acute cytotoxic responses of cultured avian and rodent aortic smooth muscle cells (SMCs) to allylamine (AAM), a selective vascular toxin. SMCs were isolated from male Japanese quail or Sprague-Dawley rats and established in culture by standard procedures. Cellular glutathione (GSH) content and lactate dehydrogenase (LDH) leakage were used as indices of cytotoxicity. Exposure of avian and rodent SMCs in primary culture to AAM (0.2-200 microM) for 4 h was associated with a significant reduction in cellular GSH and enzyme leakage in cultures of both cell types. Increased exposure time to 24 h further depleted cellular GSH levels and enhanced the leakage of LDH in primary cultures of avian SMCs. In contrast, enhanced LDH leakage occurred without further GSH depletion in primary cultures of rodent SMCs upon exposure to AAM for 24 h. Removal of serum did not modulate the cytotoxic response profile of primary cultures of avian SMCs treated with 200 microM AAM, but was associated with marked elevation in cellular GSH levels and significant LDH leakage in rodent SMC cultures. The cytotoxic responses to 0.2-200 microM AAM in secondary cultures of avian SMCs were comparable to those observed in primary culture. In contrast, AAM-induced enzyme leakage did not consistently correlate with changes in GSH content in subcultured rodent SMCs. Challenge with 200 microM acrolein (ACR) for 4 h reduced the GSH content in avian, but not rodent, subcultures of SMCs. However, significant LDH leakage occurred in subcultures of both cell types upon exposure to ACR. Although hydrogen peroxide (H2O2) did not modulate GSH levels in avian or rodent cultures, leakage of LDH was observed in rat SMCs challenged with 200 microM H2O2. Removal of serum did not alter the cytotoxic responses of avian subcultures to 200 microM AAM for 24 h, but fully prevented cytotoxicity in rodent subcultures. These data suggest that potentially significant variations in the sequence of events leading to injury may exist between quail and rat aortic SMCs. These differences may contribute to the enhanced avian susceptibility to AAM-induced aortic injury in vivo. PMID- 8360944 TI - Intrarenal distribution of inorganic mercury and albumin after coadministration. AB - The renal disposition and the intrarenal distribution of albumin and mercury were studied simultaneously in rats co-injected with a 0.5-mumol/kg dose of albumin and a 0.25-mumol/kg dose of inorganic mercury at 2, 5, 30, and 180 min after injection. These studies were carried out to test the hypothesis that one of the mechanisms involved in the renal tubular uptake of inorganic mercury is cotransport with albumin. By the end of the first 2 min after injection, the ratio of inorganic mercury to albumin in the renal cortex and outer stripe of the outer medulla was approximately 2.6 and 1.6, respectively. Both the cortex and outer stripe contain segments of the proximal tubule, and it is these segments that have been shown to be principally involved in the renal tubular uptake of both albumin and inorganic mercury. The ratio increased slightly in these two zones after 5 and 20 min after injection. These data demonstrate that there is a relatively close relationship in the renal content of inorganic mercury and albumin during the early minutes after coinjection of inorganic mercury and albumin. However, the ratios are significantly greater than the ratio of inorganic mercury to albumin in the injection solution, which was 0.5. After 180 min following co-injection, the ratio increased to about 38 in the cortex and 15 in the outer stripe. This increase in the ratio is probably related to the metabolism of albumin. Based on the ratios of inorganic mercury to albumin in the renal cortex and outer stripe of the outer medulla, it appears that some proximal tubular uptake of inorganic mercury occurs by mechanisms other than endocytotic cotransport of inorganic mercury with albumin. However, since the ratios were small during the early times after injection, cotransport of inorganic mercury with albumin cannot be excluded as one of the mechanisms involved in the proximal tubular uptake of inorganic mercury. PMID- 8360945 TI - Prednisolone enhances myogenesis and dystrophin-related protein in skeletal muscle cell cultures from mdx mouse. AB - The differentiation of skeletal muscle cells from mdx mice which lack dystrophin expression was examined after glucocorticoid treatment, namely alpha methylprednisolone (PDN). Primary skeletal muscle cell cultures were established from newborn mdx, congenic C57BL/10, and allogenic BALB/C mice. We show that PDN promotes the myogenesis of both mdx- and control mice-derived cultures as determined by 1) the number of myotubes, 2) acetylcholine receptors, and 3) dystrophin and dystrophin-related protein levels. These results support the hypothesis that PDN could enhance the myogenesis of satellite cells and increase dystrophin-related protein expression in DMD treated patients. PMID- 8360946 TI - Evidence for activation of astrocytes via reactive microglial cells following hypoglossal nerve transection. AB - Following peripheral nerve injury, resident microglial cells proliferate and astrocytes undergo hypertrophy, as evidenced, e.g., by an increase in the levels of glial fibrillary acidic protein (GFAP). In a previous study we have shown that infusion of cytosine arabinoside (ARA-C) into the rat brain blocks the axotomy induced proliferation of microglial cells. This experimental approach has been used in the present study in order to explore the issue of whether the reactive microglial cells are mediators of the increased GFAP expression in the hypoglossal nucleus of the rat following axotomy. Quantitative analysis of sections processed for immunocytochemistry or in situ hybridization demonstrated a marked increase in GFAP-like immunoreactivity and GFAP-mRNA, respectively, in the ipsilateral hypoglossal nucleus 4 and 7 days after axotomy in control experiments. These increases failed to occur in axotomized animals treated with ARA-C. Therefore, our data are compatible with the hypothesis that activation of astrocytes following axotomy as measured by increased expression of GFAP and its mRNA is induced secondarily to the microglial response. PMID- 8360947 TI - Identification of a collagen potentiated neurite promoting factor isolated from C6 glioma cells. AB - The C6 glial cell line has been used as a model cell system for the investigation of new glial produced neurotrophic and neurotropic molecules. By using the C6 cell line grown in a defined medium on collagen, this laboratory has isolated a distinct neurite promoting factor (NPF) that is potentiated by the presence of collagen (CPNPF). We have observed that C6 cells cultured in a defined medium on collagen (rat type-I) slowed their growth rate and expressed an astrocytic- or oligodendrocytic-like morphology. CPNPF, at this state of purity, appears to be a distinct NPF which induces neurite outgrowth (neurites of 1 or more somal diameters) in PC12 cells. These neurite promotion effects, however, appear to support the neuron morphology for only a short period (4 days) of time without the presence of neurotrophic factor (NTF). The neurite promoting activity is ineffective in inducing neurite outgrowth using mouse neuroblastoma cells (neuro 2a). CPNPF appears to be a heat stable protein whose activity does not depend on the presence of intact collagen, heparin sulfate proteoglycan (HSPG), or chondroitin sulfate proteoglycan (CSPG). Exposure to dissociative conditions results in a loss of neurite promoting activity. CPNPF is not a glycoprotein that contains an accessible alpha-D-mannopyranosyl, alpha-D-glucopyranosyl, or a sterically related residue (hydroxyl groups in the C-3,4, and 5 positions). Although these residues are not present on all glycoproteins, it does indicate that CPNPF is most likely not a glycoprotein. CPNPF activity is not blocked by neutralizing antibodies directed toward NGF, beta-FGF, IL-1 beta, IL-6, TGF-beta 2, TGF-beta 1.2, TGF-beta 3, TGF-beta 5, or EGF. CPNPF appears to either be oligomeric protein or a complex of proteins. On the basis of indirect evidence, it does not appear to be glial derived protease nexin-I. The alteration in morphology of the C6 glial cell line by serum-free conditions in the presence of collagen may have induced the production of a potentially new NPF not seen by previous investigators. PMID- 8360948 TI - Vesicular transport of myelin proteolipid and cerebroside sulfates to the myelin membrane. AB - The possibility that cerebroside sulfates and myelin proteolipid (PLP) could be simultaneously located in transport vesicles destined to be assembled in myelin was investigated in the brain of 20 day old rats. The brain was homogenized and fractionated according to Burkart et al. (J Biol Chem 257:3151-3156, 1982) to obtain a microsomal fraction that was further subfractionated in a linear sucrose density gradient following the procedure of Siegrist et al. (J Neurochem 33:497 504, 1979) to obtain a vesicular fraction which has been shown to transport cerebroside sulfates (Burkart et al., as above). This fraction was associated with acid hydrolase activity and had a lipid composition different from that of myelin and microsomal fractions. Studied by slab gel electrophoresis, dot blot, and Western blot analysis, using a highly specific anti-PLP antibody, it was found to contain myelin PLP. In view of previous findings of several laboratories including our own, the presence of myelin proteolipid in a vesicular fraction which is related to the transport of cerebroside sulfates gives further support to the hypothesis that the delivery of both constituents to the myelin membrane could be associated. PMID- 8360949 TI - Changes of amino acid and monoamine levels after neonatal 6-hydroxydopamine denervation in rat basal ganglia, substantia nigra, and Raphe nuclei. AB - The effects of a neonatal dopaminergic deafferentation with the neurotoxin 6 hydroxydopamine (6-OHDA) on endogenous tissue levels of catecholamines, indoleamines, and amino acids were investigated in discrete rat brain regions. After producing the lesion at postnatal day 3 by intraventricular injections of 6 OHDA, with a desipramine pretreatment to protect noradrenaline neurons, the animals were kept for 3 months. Their brains were dissected to obtain samples of neostriatum, Globus pallidus, Substantia nigra, and Raphe nuclei, which were then analyzed by high-performance liquid chromatography, coupled either to electrochemical detection for aromatic monoamines, or to post-column ninhydrin derivatization with spectrophotometry for amino acids. The neonatal 6-OHDA treatment depleted dopamine (DA) levels in neostriatum, Globus pallidus, and Substantia nigra, but in Raphe nuclei DA was increased. The main metabolites of DA were also decreased in neostriatum, Globus pallidus, and Substantia nigra but remained unchanged in Raphe nuclei. Serotonin (5-HT) and its metabolite 5-hydroxy indole-3-acetic acid increased in neostriatum and Raphe nuclei; in Substantia nigra there was a slight increase in 5-HT only. The 6-OHDA lesion caused heterogeneous alterations in amino acid contents, which varied according to the region. In the neostriatum there were increases of gamma-aminobutyric acid (GABA), aspartic acid, and glycine. In the Globus pallidus taurine, GABA, glutamic acid, glutamine, aspartic acid, serine, and alanine were elevated. In the Substantia nigra only increases in taurine, GABA, glutamic acid, and glutamine could be documented. This study shows important changes in amino acid levels and in some of their ratios, occurring in different anatomical subdivisions of the basal ganglia and related brainstem nuclei following a neonatal treatment with 6-OHDA. The results thus demonstrate major biochemical modifications in amino acids in the aftermath of a DA denervation and/or a 5-HT hyperinnervation during an early developmental period. PMID- 8360950 TI - Pentylenetetrazol seizures increase pro-nerve growth factor-like immunoreactivity in the reticular thalamic nucleus and nerve growth factor mRNA in the dentate gyrus. AB - Neurotrophins may have a neuroprotective role and are probably involved in the control of axonal sprouting and synaptic plasticity. An antibody raised against a pro-sequence of nerve growth factor (NGF) was tested. In control undisturbed rats, a strong immunoreactivity was detected in scattered cells in and around the pyramidal and granule cell layer of the hippocampus and a moderate labeling was found in the reticular thalamic nucleus. In situ hybridization showed specific expression of NGF mRNA in a similar population of scattered cells in the hippocampal formation but not in the reticular thalamic nucleus. Acute epileptic seizures, induced by a convulsive dose of 50 mg/kg pentylenetetrazol (PTZ), strongly increased NGF mRNA in neurons of the granular layer of the dentate gyrus 3 hr but not 6 hr after the injection. No change in pro-NGF-like immunoreactivity was observed in the hippocampus or reticular thalamic nucleus after acute seizures. Chemical kindling was induced by daily injections of subconvulsive doses (30 mg/kg) of PTZ for 4 weeks. This treatment significantly increased pro NGF-like immunoreactivity in the reticular thalamic nucleus but did not affect NGF mRNA. These data strengthen a role for the reticular thalamic nucleus and NGF in PTZ kindling. PMID- 8360951 TI - Expression of heterologous proteins in cultured rat hippocampal neurons using the Semliki Forest virus vector. AB - The Semliki Forest virus expression vector (Liljestrom and Garoff: Bio/Technology 9:1356-1361, 1991) was tested in cultured rat hippocampal neurons using two Madin Darby canine kidney (MDCK) cell membrane-associated proteins as reporters: rab8, a small GTPase involved in post-Golgi vesicle transport, and VIP21, an integral membrane protein of caveolae, trans-Golgi network, and post-Golgi vesicles. Expression of the c-myc epitope-tagged proteins was visualized by immunofluorescence microscopy. The proteins were first detected in neurons after 3-4 hr infection by the recombinant viruses. The infection efficiency on neurons was high: after 6 hr infection at a multiplicity of one, 50-60% of the cells expressed the reporter proteins. The neurons tolerated the infection well up to 8 hr. Their polarized organization was not disturbed, as judged from morphology and from distribution of the dendritic MAP2 and axonal synaptophysin marker proteins. The Semliki Forest virus vector thus seems suitable for short-term expression of proteins in cultured neurons. PMID- 8360953 TI - NMA seeks prescription to end violence. PMID- 8360952 TI - A piece of my mind. The learning curve. PMID- 8360954 TI - Report: health care reform must affirm 'right'. PMID- 8360955 TI - New partnership pursues research on biosensors. PMID- 8360957 TI - From the Centers for Disease Control and Prevention. Tuberculosis among pregnant women--New York City, 1985-1992. PMID- 8360956 TI - From the Food and Drug Administration. PMID- 8360958 TI - From the Centers for Disease Control and Prevention. Emergency department response to domestic violence--California, 1992. PMID- 8360959 TI - From the Centers for Disease Control and Prevention. Jin bu huan toxicity in children--Colorado, 1993. PMID- 8360960 TI - Digital rectal examination screening for prostate cancer. PMID- 8360961 TI - Digital rectal examination screening for prostate cancer. PMID- 8360963 TI - Hysterectomy, HMOs, and appropriateness. PMID- 8360962 TI - Drug interactions: the death pen. PMID- 8360964 TI - Abdominal aortic aneurysm: preoperative evaluation. PMID- 8360965 TI - Old times: nasty, brutish, and short--but at least no injected pharmaceuticals. PMID- 8360966 TI - Teaching interviewing and interpersonal skills. PMID- 8360967 TI - Continuing climb in rates of esophageal adenocarcinoma: an update. PMID- 8360968 TI - Recurrent epidemics caused by a single strain of erythromycin-resistant Staphylococcus aureus. The importance of molecular epidemiology. AB - OBJECTIVE--To compare the accuracy of clinical epidemiologic findings with results of molecular epidemiologic analysis in identifying the source of recurrent epidemics of erythromycin-resistant Staphylococcus aureus (ERSA) infections in a well-baby nursery. DESIGN--Epidemic investigations with retrospective and prospective microbiological surveillance. Staphylococcus aureus isolates were evaluated by plasmid analysis and genotyping. SETTING--A well-baby nursery in a 700-bed university teaching hospital with approximately 250 deliveries per month. PATIENTS--Newborn infants who developed ERSA infections during 1990 and 1991. INTERVENTION--Traditional infection control measures, including cohorting of infected infants and hand washing, were implemented. Personnel were cultured for nasal carriage of S aureus during both epidemics. Employees carrying ERSA were removed from the nursery and treated with mupirocin. RESULTS--In the first epidemic, 15 infants were infected with ERSA. A nursing assistant who cared for most of the infants was found to be a carrier of ERSA. She was removed from the nursery and the epidemic resolved. Fifteen months after the first epidemic ended, an epidemic that involved 11 infants began. The attending physician had a facial furuncle and was found to be a carrier of ERSA. The physician was treated and the epidemic resolved. Plasmid and genotyping showed the ERSA organisms from both epidemics were the same. The employee implicated in the first epidemic did not have the epidemic strain, but the physician who attended during both epidemics did. CONCLUSIONS--Traditional epidemic investigations may lead to false conclusions that can only be recognized with molecular epidemiologic techniques. For these techniques to be useful in the control of outbreaks, plasmid analysis and/or genotyping must be readily available. PMID- 8360969 TI - Comparison of survival probabilities for dialysis patients vs cadaveric renal transplant recipients. AB - OBJECTIVE: To compare mortality risk among cadaveric renal transplant recipients vs transplant candidates on dialysis in the cyclosporine era. SETTING: Patient mortality risk was analyzed by treatment modality for a completed statewide patient population. PATIENTS: All Michigan residents younger than age 65 years who started endstage renal disease (ESRD) therapy between January 1, 1984, and December 31, 1989, were included. Patients were followed up from ESRD onset (n = 5020), to wait-listing for renal transplant (n = 1569), to receiving a cadaveric first transplant (n = 799), and to December 31, 1989. MAIN OUTCOME MEASURE: Mortality rates. RESULTS: Using a time-dependent variable based on the waiting time from date of wait-listing to transplantation and adjusting for age, sex, race, and primary cause of ESRD, the relative risk (RR) of dying was increased early after transplantation and then decreased to a beneficial long-term effect, given survival to 365 days after transplantation (RR, 0.36; P < .001). This lower long-term risk was most pronounced (RR, 0.25) among diabetic transplant recipients compared with diabetic wait-listed dialysis patients (P < .001) and not observed among patients with glomerulonephritis as cause of ESRD (P > .05). Overall, the estimated times from transplantation to equal mortality risk was 117 +/- 28 days and to equal cumulative mortality was 325 +/- 91 days. CONCLUSIONS: The overall mortality risk following renal transplantation was initially increased, but there was a long-term survival benefit compared with similar patients on dialysis. These analyses allow improved description of comparative mortality risks for dialysis and transplant patients and allow advising patients regarding comparative survival outcomes. PMID- 8360970 TI - Racial equity in renal transplantation. The disparate impact of HLA-based allocation. PMID- 8360971 TI - Holes in the Jackson Hole approach to health care reform. PMID- 8360973 TI - Climbing 'the learning curve'. New technologies, emerging obligations. PMID- 8360972 TI - Molecular epidemiology and its clinical application. PMID- 8360974 TI - Seronegative Lyme disease. PMID- 8360975 TI - Metallic taste. PMID- 8360976 TI - Cholecystokinin-enhanced cholescintigraphy in the diagnosis of gallbladder disease. PMID- 8360977 TI - [Activities of antibiotics against methicillin-resistant Staphylococcus aureus with particular reference to synergetic effect between ticarcillin and fosfomycin on penicillinase non-producing methicillin-resistant S. aureus]. AB - We tested susceptibilities of 46 strains of clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) to arbekacin (ABK), tobramycin (TOB), ticarcillin (TIPC), clavulanic acid/ticarcillin (CVA/TIPC) and fosfomycin (FOM). Twelve strains had penicillinase activity. Most strains were resistant to TOB, TIPC, FOM and CVA/TIPC, but ABK inhibited 80% of the 46 MRSA strains at a concentration of 1.56 microgram/ml. The combination of ABK and FOM was indifferent. Synergism was observed, however, between FOM and TIPC against 79% of penicillinase non-producing MRSA. This synergism may mean that FOM inhibits the production of penicillin-binding protein 2' in some strains of penicillinase non producing MRSA. PMID- 8360978 TI - [Antimicrobial activity of clarithromycin and its effect on bacterial adherence to medical material]. AB - Antimicrobial activity of clarithromycin (CAM) in comparison with other 6 macrolides was determined against 419 recent clinical isolates including Streptococci, Enterococci, Staphylococci, Moraxella, Haemophilus and Bacteroides strains. MICs80's of CAM against Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus agalactiae were 0.78, 0.10 and 0.10 microgram/ml, respectively. MICs80's against Moraxella catarrhalis and Haemophilus influenzae were 0.05 and 1.56 micrograms/ml, respectively. Laboratory-induced resistance to CAM in strains of S. pneumoniae, Enterococcus faecalis or methicillin-sensitive Staphylococcus epidermidis occurred in stepwise fashion and at a very low rate. Adherence to silicon filter of strains of Pseudomonas aeruginosa or S. epidermidis was strongly repressed by the addition of sub-MIC of CAM or other macrolides. Although tosufloxacin (TFLX) alone had no bactericidal activity against the sessile cells of P. aeruginosa strains tested, TFLX showed synergistic bactericidal activity when combined with sub-MICs of CAM or erythromycin. PMID- 8360979 TI - [Usefulness of (1-->3)-beta-D-glucan measurement for diagnosis of deep mycosis]. AB - The number of deep mycosis has been increasing because of increases in immunocompromised hosts and in fungal colonization associated with increasing use of broad-spectrum antibacterial antibiotics. Based on these phenomenon, a simple test method for an early diagnosis of deep mycosis is urgently desired. We therefore investigated the usefulness of assaying a fungal cell component, (1- >3)-beta-D-glucan (beta-glucan). The amount of beta-glucan was obtained from the difference between the amounts determined using Toxicolor and Endospecy, and the serum levels of more than 10 pg/ml were considered positive signs for beta glucan. The following results were obtained: We found that beta-glucan was positive in 75% of the patients who had been definitely diagnosed to have mycosis, and in 58.3% of the patients strongly suspected of mycosis. The numbers of beta-glucan positive patients' in these 2 groups of patients were significantly different from that in those without mycosis (14.7%, P < 0.05). Thus a usefulness of beta-glucan measurement for the diagnosis of mycosis was demonstrated. However, beta-glucan was sometimes negative even in patients with fungemia at an early phase of the disease and turned positive several days later. Even in a patient with definite lung mycosis, who had a latent circumscribed lesion (afebrile and CRP-negative), beta-glucan was also negative. From these findings, one should be aware that the beta-glucan test produces false negatives even in patients with definite mycosis and that the test should be repeated during the course of the disease. PMID- 8360980 TI - [Antimicrobial activities of cefminox against recent clinical isolates]. AB - Against main clinical isolates at our center in 1990 to 1992, the minimum inhibitory concentrations (MICs) of cefminox (CMNX) and some other comparable cephems were determined. The results are summarized as follows. 1. As to the strains resistant to cephems including CMNX, annual increases were observed for Streptococcus pneumoniae among Gram-positive bacteria and Proteus vulgaris among Gram-negative bacteria. Moreover, cephem-resistant strains of Escherichia coli were constantly isolated, and there were signs indicating that cephem-resistant strains would increase among strains of Klebsiella pneumoniae. 2. The annual increases in cephem-resistant strains of S. pneumoniae and P. vulgaris may respectively reflect the recent increases in the incidence of benzylpenicillin (PCG)-insensitive strains of S. pneumoniae (PISP) and multi-drug resistant strains including oxime type cephems and new quinolones introduced into clinical use in the latter half of the 1980s. 3. Concerning antimicrobial activities of CMNX against recent clinical isolates, the same problems as described above will remain. However, these tendencies have been observed only with regard to MIC90. No remarkable changes have been noted for MIC50 or MIC80 at this time. PMID- 8360981 TI - [A nationwide survey of antimicrobial susceptibilities of clinical isolates to antibiotics in Japan (1988-1990)]. AB - This study was conducted to investigate susceptibilities of clinical isolates to antibacterial agents at 149 hospitals throughout Japan from September to December in both 1989 and 1990. In this study, identifications and susceptibility testings were carried out at each hospital laboratory. The susceptibility testings were performed according to the disk diffusion method recommended by NCCLS. Staphylococcus aureus and coagulase-negative staphylococci showed high or moderate resistance rates to beta-lactam antibiotics, but Streptococcus pyogenes and Streptococcus pneumoniae were highly susceptible to them. Enterococcus faecalis was susceptible to imipenem (IPM) and piperacillin but resistant to beta lactam antibiotics and aminoglycosides. Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were susceptible to beta-lactam drugs and aminoglycosides. Enterobacter cloacae, Serratia marcescens, Proteus vulgaris, Morganella morganii and Pseudomonas aeruginosa had a good susceptibility to IPM and aminoglycosides. Bacteroides fragilis was highly susceptible to IPM. IPM had strong antibacterial activity to many species of clinical isolates, including strains which were resistant to commonly used antibiotics. PMID- 8360983 TI - In vitro antimicrobial activities of lactoferrin, its concomitant use with cefpodoxime proxetil and clinical effect of cefpodoxime proxetil. AB - As one of the biodefense mechanisms, lactoferrin (LFN) in the secreta of female genital organ may be an interesting biological material in view of its antimicrobial activity. In the present study, we investigated antimicrobial activities of LFN and its combination with cefpodoxime proxetil (CPDX-PR), we also as evaluated clinical effect of CPDX-PR. The following results were obtained. 1. Antimicrobial activities of LFN were tested against 15 strains of 10 species of bacteria, and potent activities against Staphylococcus aureus 209P, Escherichia coli, Klebsiella pneumoniae and Proteus spp. were found. 2. In a concomitant use of LFN with CPDX-PR (a checkerboard method), synergistic actions were observed against S. aureus 209P, E. coli STf, K. pneumoniae 602 and Pseudomonas aeruginosa 1046, and additive actions against E. coli NIHJ and Providencia rettgeri 1603. In 3 strains, the MICs of CPDX-PR in the presence of LFN were reduced to < 1/64. 3. In the evaluation of clinical effect of CPDX-PR, efficacy rates were 53/57 (92.9%) in a patient group with infections. The incidence of adverse reaction was 0/57. PMID- 8360982 TI - [Therapeutic efficacy of cefodizime in combination with aminoglycosides against systemic infections caused by Pseudomonas aeruginosa in immunocompromised tumour bearing mice]. AB - In vivo synergistic effects of cefodizime (CDZM) were investigated in combination with aminoglycosides (AGs), sisomicin (SISO) or dibekacin (DKB) against Pseudomonas aeruginosa in immunocompromised tumour bearing mice. Fractional effective dose (FED) indices showed that either synergistic or additive effects were observed between CDZM and AGs. The synergistic intraperitoneal bactericidal effect of CDZM in combination with SISO or DKB was also observed in immunocompromised tumour bearing mice. The post antibiotic effect (PAE) of AGs was prolonged by the addition of CDZM. Moreover, the strong synergistic bactericidal effects of CDZM and AGs against P. aeruginosa were observed in the presence of immunocompromised tumour bearing murine polymorphonuclear leukocytes (PMN). These results suggest that the strong therapeutic efficacy of CDZM in combination with AGs was caused by synergistic bactericidal effect of CDZM and AGs in the presence of PMN. PMID- 8360984 TI - [An evaluation of a therapy with antibacterial and antifungal agents infections with hematological disorders]. AB - The primary objective of this study is to confirm the efficacy and safety of combination therapy with antibacterial and antifungal drugs for patients with hematological disorders complicated with infections of unknown causative organisms. The subjects consisted of 55 patients with hematological disorders, 28 males and 27 females, ranging from 1 to 78 years of age, with an average age of 34 years. The breakdown of the patients by disease was: 41 leukemias, 10 malignant lymphomas, 3 myelodysplastic syndromes and an aplastic anemia. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) and aminoglycoside (AG) plus fluconazole (FLCZ) as an empiric therapy. Overall efficacy rate was 54.5% for all the patients: 57.7% for patients with suspected sepsis and 0% for those with pneumonia from which unknown organisms were detected. The efficacy rate was 59.4% for patient who had been previously treated with other antibiotics and 47.8% for those who had not previously been treated. The above results suggested that this combination therapy might be effective for severe infections of unknown causative organisms associated with hematological disorders. PMID- 8360985 TI - [GPI-anchored proteins and paroxysmal nocturnal hemoglobinuria]. PMID- 8360986 TI - [Treatment of aplastic anemia with antithymocyte globulin, Lymphoser Berna]. AB - Twenty-four patients with aplastic anemia (19 severe: 5 moderate) were treated with combined immunosuppression consisting of antithymocyte globulin (ATG: Lymphoser Berna, Swiss Serum and Vaccine Institute Berne) and high-dose methylprednisolone. Danazol or meptiostane was administered concurrently for at least 3 months. Three batches of ATG were used, two were not absorbed with thrombocytes and one was absorbed with thrombocytes for the prevention of thrombocytopenia. Nine of 20 evaluable patient (45%) had sustained improvement in hematopoiesis within 3 months of treatment. Nine of 14 patients (64%) showed a response to ATG without thrombocyte absorption, on the other hand, none of 6 patients responded to ATG with thrombocyte absorption. By life table analysis, the 3 year probability of survival was 81 +/- 27% after the combined immunosuppressive therapy. These results indicated that ATG therapy was very effective in Japanese patients with aplastic anemia. PMID- 8360987 TI - [Estimation of megakaryothrombopoiesis by mean platelet volume in leukemia patients during the course of chemotherapy and patients undergoing bone marrow transplantation]. AB - The mean platelet volume (MPV) was measured in 14 patients with acute leukemia during the course of chemotherapy for remission induction and 21 patients undergoing bone marrow transplantation, in order to assess its usefulness as an indicator for megakaryothrombopoiesis at bone marrow suppression and recovery. In patients with acute leukemia, the MPV fell from 9.7 +/- 0.8 fl to 9.2 +/- 0.4 fl during the myelosuppression, and then it rose transiently to 10.2 +/- 0.5 fl and fell to 9.3 +/- 0.5 fl during recovery of platelet count. Similarly, in patients undergoing bone marrow transplantation, the MPV elevation was followed by the recovery of platelet count. Thus, when engraftment was defined as this MPV elevation, engraftment was confirmed significantly earlier by MPV (19.9 +/- 5.8 days) than by platelet count (24.8 +/- 6.7 days). MPV should be a useful indicator for engraftment or recovery from marrow aplasia in cases of acute leukemia and those of bone marrow transplantation. PMID- 8360988 TI - [Chronic myelomonocytic leukemia and esophageal cancer developed in a renal allograft recipient]. AB - A 46-year-old man treated with azathioprine (100-150 mg/day) and prednisolone (10mg/day) for 14 years after allogeneic renal transplantation, was admitted to our hospital in December, 1988 for the evaluation of leukocytosis. His leukocyte count was 32,700/microliters with 38% monocytes and 2% blasts. Chromosomal analysis of the bone marrow revealed 45, XY, -7. He was diagnosed as chronic myelomonocytic leukemia (CMML), and treated with low-dose Ara-C. Two months later, he progressed to overt acute leukemia, and he complained of difficulty in swallowing. Endoscopic examination revealed esophageal cancer. The patient died of respiratory failure on April 18, 1989. This case suggests that immunosuppressive agents might play an important role on the pathogenesis of CMML and esophageal cancer. PMID- 8360989 TI - [Plasma exchange failures in two patients with thrombotic thrombocytopenic purpura]. AB - We treated two patients with thrombotic thrombocytopenic purpura (TTP) with multiple plasma exchanges for a short period. Following 6 plasma exchanges during 11 days in patient 1 and the 8 exchanges during 13 days in patient 2, consciousness disturbance and thrombocytopenia improved with a decrease in serum lactate dehydrogenase (LDH) levels in both patients. However, thrombocytopenia rapidly progressed with a rise of serum LDH levels after a few days from cessation of the treatment. They received a few rounds of plasma exchange without beneficial effects and eventually died of massive hemorrhage. The clinical course of these patients indicates that some patients with TTP are refractory to repeated plasma exchanges for a short period. It seems important to determine the target point in blood chemistry values such as the LDH level for plasma exchange at which the treatment could be discontinued without causing relapse of TTP. PMID- 8360990 TI - [A case of Evans' syndrome in which CD4+CD45RA+ cells markedly decreased in its active phase]. AB - A 38-year-old man was admitted to our hospital because of exertional dyspnea in February, 1990. The patient had already been diagnosed as having autoimmune hemolytic anemia (AIHA) in February, 1982 and treated with prednisolone (PSL) until January, 1988. The laboratory examination confirmed the relapse of AIHA (IgG-warm type) and additionally disclosed the marked decrease of CD4+CD45RA+/CD4+ ratio in peripheral blood lymphocytes. Thereupon, the patient was treated again with PSL and entered the remission in one month. Simultaneously, CD4+CD45RA+/CD4+ ratio also increased to the normal level. Afterwards, the remission had been maintained for about six months with a small dose of PSL. However, in September, 1990, the hemolysis relapsed with marked thrombocytopenia and decreased CD4+CD45RA+ ratio. Then the diagnosis was corrected to Evans' syndrome because PAIgG was highly elevated together with positive Coombs' test. Although danazol and azathioprine were administered in addition to PSL, the disease remained in active phase. Thus, splenectomy was carried out in March, 1992. Consequently, the patient entered the remission that has been maintained over six months. CD4+CD45RA+/CD4+ ratio was also normalized. These results suggest that CD4+CD45RA+ cells may play an important role in the pathogenesis of AIHA or Evans' syndrome. PMID- 8360991 TI - [Mediastinal widening simulating relapse in a case of Hodgkin's disease]. AB - The appearance of a mediastinal mass in a patient with Hodgkin's disease in remission frequently indicates recurrence. However, benign processes such as rebound hyperplasia of the thymus gland should be included in the differential diagnosis. The authors present a case in which an anterior mediastinal mass was revealed by a routine chest radiograph 3 months after completion of combined modality treatment with low-dose radiation and MOPP chemotherapy for cervical Hodgkin's disease, stage I, nodular sclerosis. As the patient was clinically well with no other laboratory evidence of disease, recurrence was considered unlikely. Benign thymic enlargement was strongly suspected on the basis of striking resolution of the mediastinal mass after treatment with a short course of oral prednisolone. Thymic rebound in our case occurred coincidentally with the restoration of normal immune functions after removal of the stress imposed by antineoplastic treatment. The patient has remained free of disease recurrence for more than 20 months after cessation of therapy. Awareness of the possible benign etiology of a mediastinal mass may avert a diagnostic surgical exploration and also unnecessary adjuvant therapy. PMID- 8360992 TI - [Effectiveness of dapsone on refractory immune thrombocytopenia in a patient with systemic lupus erythematosus associated with sarcoidosis]. AB - A 57-year-old man was admitted with massive nasal bleeding and blurred vision in January, 1991. Laboratory examination showed a prominent decrease of platelet number (1,000/microliters) and a marked elevation of PAIgG (4,025 ng/10(7) cells). Serological test revealed positive antinuclear factor, low concentration of C3 and C4, high level of immune complex and polyclonal hypergammaglobulinemia. The patient had uveitis and bilateral hilar lymphadenopathy with a high level of serum lysozyme and negative PPD skin test. The diagnosis of SLE complicated with thrombocytopenia and sarcoidosis was made. In spite of the various trials of treatment, such as oral prednisolone (PSL), methyl-PSL pulse therapy, plasma exchange, high-dose intravenous gammaglobulin, cyclophosphamide, azathioprine, vincristine, colchicine, cyclosporine-A, mizoribine, danazol, ascorbic acid and interferon alpha 2b, the platelet number could not be raised enough to keep more than 10,000/microliters, though the level of PAIgG decreased to 200 ng/10(7) cells. Finally, the administration of 75 mg/day of dapsone brought about a significant rise in platelet number within 2 weeks. The maximum number of 6.2 x 10(4)/microliters was obtained after 2 months. Then the patient stopped himself to take the drug, but the platelet number remained around 4-5 x 10(4)/microliters. Same dose of the drug was again prescribed to confirm the effect of dapsone. The platelet number increased to 7.9 x 10(4)/microliters in 2 weeks, and gradually returned to 5 x 10(4)/microliters after cessation of the drug. Thus being certainly effective against thrombocytopenia, dapsone should be considered as one of the therapeutic choice for refractory autoimmune thrombocytopenia. PMID- 8360993 TI - [Distribution of cofactor-dependent anti-cardiolipin antibodies in collagen diseases]. AB - Cofactor-dependent IgG anti-cardiolipin antibodies (ACA) were examined in sera from various connective tissue diseases by ELISA using purified human beta 2 glycoprotein I. The frequency and titer of cofactor-dependent IgG ACA were higher in patients with SLE than in those with other diseases, such as RA, SSc, PM/DM, overlap syndrome, and MCTD. The predictive value for SLE was 95%. However, all of the ACA were not cofactor-dependent in SLE patients. These results indicated that cofactor-dependent IgG ACA were specific for SLE patients, but the epitopes of ACA were heterogenous, depending on various clinical manifestations. PMID- 8360994 TI - [A case of primary non-Hodgkin lymphoma of the adrenal gland presenting with Addison's disease]. AB - A 69-year-old male was admitted to our hospital complaining of skin pigmentation. Masses in bilateral adrenal glands were noted on computed tomography. An exploratory laparotomy revealed malignant lymphoma confined to the bilateral adrenal glands. Histological diagnosis was diffuse mixed-cell type, B-cell lymphoma. Laboratory tests disclosed an elevated ACTH level and decreased urinary 17KS and 170HCS secretion. Based on hypofunction of adrenal glands and skin pigmentation, the patient was diagnosed as having Addison's disease. After complete remission with combination chemotherapy, adrenal function recovered normal and pigmentation disappeared, Addison's disease is an extremely rare complication of primary malignant lymphoma of the adrenal gland. PMID- 8360995 TI - [Various endocrine syndromes of the thyroid gland]. PMID- 8360996 TI - [Various endocrine syndromes of the adrenal gland]. PMID- 8360997 TI - [Various endocrine syndromes of male sex function]. PMID- 8360998 TI - [Various endocrine syndromes of female sex function]. PMID- 8360999 TI - [Various endocrine syndromes of sex differentiation and growth]. PMID- 8361001 TI - [Endocrine syndrome]. PMID- 8361000 TI - [Various endocrine syndromes of the brain and pituitary gland]. PMID- 8361002 TI - [Carcinogenesis and oncogenes]. PMID- 8361003 TI - [Evaluation of AgNORs in lung cancer]. PMID- 8361004 TI - [AgNORs in prostatic and thyroid cancer cells]. PMID- 8361005 TI - [Anti-endometrial cancer monoclonal antibody "MSN-1" and its application to EmC EIA method]. PMID- 8361006 TI - [Cytoskeleton]. PMID- 8361007 TI - [Genetic alterations in gastric cancer with special reference to the histological type]. PMID- 8361008 TI - [Tumor suppressor gene and cytodiagnosis--p53 expression in urinary cytology]. PMID- 8361009 TI - [Flow & image cytometry and clinical applications in cancer diagnosis]. PMID- 8361010 TI - [Flow cytometric DNA analysis of renal cell carcinoma and its relationship to tumor grading, tumor stage and prognosis]. PMID- 8361011 TI - [Application of molecular technology for cytologic study]. PMID- 8361012 TI - [General remarks of methods for analyzing proliferative characteristics of the cells]. PMID- 8361013 TI - [Advances in diagnostic procedures for detection of pheochromocytoma]. AB - Pheochromocytoma arises from chromaffin tissue, usually in the adrenal medulla, and is a cause of curable hypertension. In most cases, clinical acumen alone is not sufficient to diagnose pheochromocytoma. Therefore, the diagnosis of this disorder has become almost totally dependent on laboratory test results. The most widely used biochemical procedures for detection of pheochromocytoma are measurements of urinary catecholamines or their metabolites, such as vanillylmandelic acid (VMA) or total metanephrine (MN). Traditional spectrophotometric and fluorometric methods for urinary catecholamines and their metabolites are being replaced by highly sensitive and selective chromatographic methods. Plasma noradrenaline and adrenaline measurements are of additional diagnostic value in determining recent catecholamine release and response to clonidine suppression. For either urine or plasma measurements, appropriate patient preparation, sample collection and method validation along with an understanding of the variable pattern of catecholamine secretion and metabolism in pheochromocytoma are essential. Localization of tumors is important for the surgeon and is accomplished by CT scan, 131I-metaiodobenzylguanidine scintiscans or abdominal aortography. PMID- 8361014 TI - [Pituitary system with special reference to pituitary antibodies]. AB - Amino et al. postulated a postpartum autoimmune thyroid syndrome and Sugiura et al. established an assay for detecting antibodies to anterior pituitary cell surface membrane (PCSA) by immunofluorescent methods. Using this technique, we attempted to determine the prevalence of PCSA before and after delivery. Studies were conducted with 16 pregnant women without any apparent diseases. Serial measurements of PCSA from the sera of each woman before and after delivery were performed by immunofluorescent methods using AtT-20 cells (mouse ACTH secreting cells) and GH3 cells (rat prolactin and GH secreting cells). Antibodies to AtT-20 cells were detected in 5 of 16 pregnant women at 36 weeks (31.3%), while those to GH3 cells were detected in 3 cases (18.8%). Following delivery, positive antibodies were observed in 12 women (75.0%) at 1 month, 15(93.7%) at 3 months and 13 (81.3%) at 6 months. A similar result also was obtained with GH3 cells. It is possible that some of the patients with positive antibodies have functional abnormalities of the anterior pituitary. The results obtained suggest the presence of postpartum autoimmune endocrine syndrome at the anterior pituitary level. PMID- 8361015 TI - [Gastrointestinal hormones: recent developments]. AB - Progress in gastrointestinal hormone research has increased our knowledge in peptide hormone biochemistry and gastrointestinal physiology considerably. However, this knowledge has not yet helped our understanding of common gastrointestinal diseases. More specific and reliable methods are needed to prove or to exclude the participation of gastrointestinal peptides in the pathogenesis of gastrointestinal diseases. Peptide hormones are potentially useful as diagnostic and therapeutic modalities in the practice of gastroenterology. PMID- 8361016 TI - [Dynamic changes in polymorphonuclear cell elastase-alpha 1 protease inhibitor complex, a stress marker, in various pulmonary diseases]. AB - Polymorphonuclear cell elastase-alpha 1 protease inhibitor complex (PMN elastase alpha 1 PI complex), which increased in peripheral venous blood during many inflammatory diseases, showed significant transpulmonary difference (ie. mixed venous blood < arterial blood, p < 0.05) in patients with pulmonary disorders (N = 64) but not in those with nonpulmonary disorders (N = 15). Further, PMN elastase-alpha 1 PI complex exhibited higher values in arterial blood than in peripheral venous blood (p < 0.01). Taken together, this evidence suggests intrapulmonary production of PMN elastase-alpha 1 PI complex and suggests potential lung damage due to released PMN elastase. Increased and sustained elevated levels of PMN elastase-alpha 1 PI complex in acute respiratory failure with/without adult respiratory distress syndrome showed resistance to intensive medication suggesting that PMN elastase may be a good prognostic marker. PMID- 8361017 TI - [Bronchial provocation test in bronchial asthma]. AB - Methacholine provocation test, bronchial reversibility test, aspirin inhalation test, and cough provocation test have been performed at our institute to examine pathophysiology and to diagnose bronchial diseases. Bronchial responsiveness to methacholine correlated to baseline pulmonary functions, especially to % predicted value of forced expiratory volume in 1 second (%FEV1) in asthma and sinobronchial syndrome. Bronchial reversibility was greater with beta 2-agonists than with muscarinic antagonists in asthma while it was less with beta 2-agonists than with muscarinic antagonists in sinobronchial syndrome. Our protocol for aspirin inhalation test consists of a screening test and threshold measurement test and is useful for diagnosis of analgesics-induced asthma. Capsaicin provocation test to measure airway cough receptor sensitivity is used to diagnose chronic cough. PMID- 8361018 TI - [Analysis of platelet-activating factor and its effect on the lung]. AB - One of the lipid mediators, platelet-activating factor (PAF), is reported to be involved in a variety of biological phenomena including not only harmful reactions such as allergy or inflammation, but also physiological phenomena like nerve cell differentiation, sperm mobilization, ovulation, implantation, parturition etc. We reviewed the methods of detecting PAF in biological fluids and the effects of PAF on fetal lung maturation and pulmonary diseases. Fetal lung has a capacity to produce PAF and this autacoid is involved in glycogen breakdown to furnish both glycerol backbone, such as dihydroxyacetone phosphate and glycerol-3-phosphate, and the fatty acids utilized to synthesize pulmonary surfactant. PAF also enhances secretion of pulmonary surfactant. However, PAF causes eosinophil recruitment to the lung, activation of eosinophil and neutrophil, bronchoconstriction, and lung edema, and increases bronchial hyperreactivity. All are characteristics of the pathophysiology of bronchial asthma. We examined PAF acetylhydrolase activity in plasma from patients with bronchial asthma, and found the activity was significantly lower in severe cases than that in mild or moderate cases. Ketotifen had no effect on this enzymatic activity. Evaluating PAF acetylhydrolase activity may help determine the severity of bronchial asthma. PAF is also involved in chronic lung disorders of newborns, such as bronchopulmonary dysplasia. We treated a 3-month-old child with frequent pulmonary problems who was made a diagnosis of bronchopulmonary dysplasia during neonatal period. After administration of Ketotifen for one and a half months, his clinical symptoms improved dramatically. PMID- 8361019 TI - [Usefulness anti-PPD antibody in the medical practice of tuberculosis]. AB - The decline rate of tuberculosis has decreased recently in Japan. One of the problems is the tendency of increasing doctor's delay in the diagnosis of tuberculosis. One of measures against this problem is to develop a new laboratory diagnostic method. We studied anti-PPD (Purified Protein Derivative of tuberculin) antibody in serum, pleural effusion, and bronchoalveolar lavage fluid (BAL), and found its clinical usefulness in the medical practice of tuberculosis. Firstly the methods of enzyme linked immunosorbent assay (ELISA) for the antibody to PPD were examined. The expression of antibody titer in optical density was found to be the most accurate and most simple method, and was applied in this study. IgG, IgM and IgA antibody to PPD were measured in serum, BAL and pleural effusion obtained from 122 patients with pulmonary tuberculosis, 54 patients with tuberculous pleurisy, 39 patients with lung cancer, 39 patients with malignant pleurisy, 37 patients with pneumonia, 26 patients with chronic bronchitis, 51 patients with sarcoidosis, or 49 control subjects. Serum level of IgG, IgM, and IgA antibody to PPD was elevated in tuberculosis compared with those in other diseases or control subjects. The difference was most distinctive in IgG antibody. Serum IgG antibody was higher in chronic case than in acute case and IgM antibody was higher in acute case than in chronic case. IgG, IgM and IgA antibody in pleural effusion was elevated in tuberculous pleurisy compared with those in malignant pleurisy. IgG antibody was higher in chronic tuberculous pleurisy than in acute tuberculous pleurisy and IgM antibody was higher in acute pleurisy than in chronic one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361020 TI - [Usefulness of BAL in understanding of pulmonary diseases]. AB - Since the introduction of bronchoalveolar lavage (BAL) by Reynolds, et al. in 1974, direct examination of cells from interest sites in the lung has generated great progress in our understanding of pulmonary diseases. In the present study, BAL and the clinical usefulness of BAL in diagnosing and treating pulmonary diseases were described. In addition, recent research using BAL to elucidate the fundamental mechanism of pulmonary granulomatous disorders was also described. PMID- 8361021 TI - [Detection of drug resistant-genes in cisplatin-resistant colon carcinoma cells by RT-PCR assay. II]. AB - The c-fos, c-Ha-ras and c-myc oncogenes have been proposed to play an important role in DNA synthesis. Expression of c-fos, c-Ha-ras and c-myc genes were compared with the human colon carcinoma cell line HCT8S cells and a subline that was 4.5 resistant to cis-diamminedichloro-platinum (cisplatin). Resistant cells (HCT8DDP) exhibited a 4.0, 2.8 and 1.1 fold in mRNA for these genes when compared with the parent cells by Northern blotting analysis, respectively. The reverse transcription (RT)-PCR method has been demonstrated to quantify a sequence of these oncogenes. This method allowed the detection of gene expression from minimal cells. Thus RT-PCR assay could be an effective device in th early detection of oncogenes to cisplatin-resistance. PMID- 8361022 TI - [Detection of human parvovirus B19 DNA using PCR and serological test using ELISA for diagnosis of infection]. AB - The development of a polymerase chain reaction (PCR) method for detection of human parvovirus B19 DNA and serological test of clinical specimens using ELISA is described. Of 43 serum (or plasma) samples, 29 were found to be positive for B19 DNA using the PCR, anti-IgM was detected in 16 specimens and anti-IgG in 25. In all specimens confirmed to contain B19-specific IgM, the presence of B19 DNA was demonstrated. Furthermore, B19 DNA was demonstrated in a patient with B19 infection for a longer period of time than was anti-IgM. In addition, we discuss the diagnosis of B19 infection using anti-IgG, in the acute stage and convalescent stage. In fetal infection, the PCR method provides sufficient detection of B19 DNA in cord blood, amniotic fluid, ascitic fluid, and fetal pericardial effusion and pleural effusion. PMID- 8361023 TI - [Development of an enzymatic fluorescence method for detecting of cholesterols in circulating monocyte]. AB - Since the infiltration of macrophage/monocyte into the arterial intima would be the first and most important step to developing the atherosclerosis, it is important to analyze the lipid composition not only in the circulating blood but also in the cell. We developed the high sensitive enzymatic assay method of total and free cholesterol and employed this assay to the measurement of monocyte cholesterol ester. Diabetic patients had high total cholesterol and cholesterol ester of monocyte. The elevated monocyte cholesterol ester was related to the LDL cholesterol and Lp(a) concentrations in the plasma. PMID- 8361024 TI - [Evaluation of an enzyme-linked immunosorbent assay for the determination of prothrombin fragment F1.2 (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.) using micro-titer plate]. AB - Prothrombin fragment F1.2 (F1.2) is a new molecular marker indicating acceleration of blood coagulation. We evaluated a new assay of F1.2 measurement using a micro-titer plate (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.). The assay obtained satisfactory results in intra-assay reproducibility test, inter-assay reproducibility test, dilution linearity test and in vitro recovery test. Normal values of plasma F1.2 were 0.16 +/- 0.09 nmol/l (mean +/- SD) in 108 healthy individuals. Differences in the levels between the sexes were not significant. In patients with DIC (n = 22), plasma F1.2 levels were significantly higher than in normal healthy individuals and were correlated with the levels of thrombin-antithrombin III complex. These findings suggest that this F1.2 assay using a micro-titer plate is clinically useful for the evaluation of the therapeutic effect and diagnosis of hypercoagulable states like DIC. PMID- 8361025 TI - [Studies on the fragments of FDP in 3 non-DIC patients with increased FDP levels in the sera]. AB - We previously studied fibrinolysis and fibrinogenolysis by analyzing fragments of fibrin/fibrinogen degradation products (FDP) employing sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. In this report, we characterized the fragments of FDP in three patients with increased serum FDP, that were caused by various diseases. In the patient suffering from tuberculous constrictive pericarditis (case 1), the most part of the FDP fragments were DD and D. In the patient suffering from infection in addition to liver cirrhosis (case 2), the most part of the FDP fragments were high molecular weight (HMW) and D. In case 1 and 2, serum FDP levels were increased in parallel with the elevations of CRP levels. Although DD and HMW fragments were remarkably increased in case 1 and 2 with our immunoblotting analysis, DD levels assayed with LPIA system were much lower than FDP levels. The reason this discrepancy was explained by the observation that affinities of the monoclonal antibody used in LPIA system with DD and HMW fragment were markedly lower than that to DD-E fragment. In the patient suffering from deep vein thrombosis probably caused by steroid therapy of nephrotic syndrome (case 3), the most part of detected FDP fragments were DD and HMW in the period when APTT was shorter than normal, whereas D was mainly observed in the period when APTT was normal. In case 3, FDP and DD levels were increased in parallel with the shortening of APTT. In these non-DIC patients, increased serum FDP levels were induced by the presence of ascites and/or pleural effusion plus infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361026 TI - [Clinical preventive medicine in cancer diagnosis--proposal for a new cancer diagnostic system in an aging society]. AB - To enroll a large percentage of the cancer high-risk group and to simultaneously screen for various kinds of cancer, a modified combination assay of tumor markers and risk factors in serum was devised. A pilot study using 5 tumor markers, AFP, CEA, CA19-9, CA125, Dupan-2, as well as 3 risk factors of pepsinogen, PGI, PGII, PGI/II, showed 87.0% sensitivity and 58.8% specificity in 54 patients with various cancers and 163 healthy subjects. Eighty percent of stage I or II cases were detected except for one stage I case of right lung cancer and one stage II case of oral cavity cancer. Field work is now under way to detect various cancers among approximately 1000 inhabitants above 50 years of age in a particular town using 11 tumor markers and 3 risk factors. One hundred fifty three of 967 cases (male 372, female 595) showed various abnormal values and some were examined further as higher risk cases to detect particular cancers suspected from the results of the modified combination assay. At present, 5 PAP positive cases were referred to urological clinic for examination and 3 were confirmed histologically as prostatic cancer. This corresponds to approximately a 0.8% of detection rate which is more than 40 times the prostatic cancer mortality. Other kinds of cancer are still under investigation at various specified clinics. If cancer is not detected in these higher risk cases, they will be followed year to year. Further, the most suspicious cases will be examined at a chromosome or DNA level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361027 TI - [Borderline values of laboratory data in patients with hyperlipidemia]. AB - In Japanese, serum cholesterol levels have been increasing. This seems to be due to changes in life style, mainly the increase in dietary fat. Epidemiologic studies in the United States and Europe have shown that patients with hypercholesterolemia have a high risk of ischemic heart disease. Some guidelines for the management of hyperlipidemia have been developed in the United States, Europe, and Japan. The National Cholesterol Education Program (NECP) in the United States divides serum cholesterol level into three grades (desirable: below 200 mg/dl, borderline: between 200 mg/dl and 240 mg/dl, hypercholesterolemia: over 240 mg/dl). Borderline serum cholesterol is also a risk, especially in people complicated by other risk factor(s). As most borderline serum cholesterol seems to be due to polygenic hypercholesterolemia, an attempt to change the diet should be the first recommendation for treatment. PMID- 8361028 TI - [Borderline hypertension]. AB - According to WHO criteria in 1978, borderline hypertension is defined as systolic blood pressure between 140 and 159 mmHg and/or diastolic blood pressure between 90 and 94 mmHg. Compared with direct intravascular pressure measurement, values obtained by the conventional cuff method were 2 mmHg lower in systolic pressure and 2 mmHg higher in diastolic pressure. The precision of the cuff method was approximately +/- 4 mmHg in both systolic and diastolic pressures. In 20 patients with mild hypertension, arterial pressure fluctuated with respiration within ranges from 6 to 32 mmHg in systole and from 3 to 14 mmHg in diastole. From these results, repetitive blood pressure measurements are recommended for the diagnosis of borderline hypertension. Borderline hypertension is the most sensitive predictor of definite hypertension in the future. Long term follow up should be stressed. PMID- 8361029 TI - [The boundary levels of laboratory data in autoimmune diseases]. AB - The clinical significance of rheumatoid factor, antinuclear antibody, anti thyroid antibody, CH50 and serologic tests for syphilis (STS) in boundary levels were investigated. The boundary levels were tentatively determined as: RF 5-20 U/ml, ANA 20-40X, anti-thyroid antibody 100-400X and CH50 25-30 U/ml. In STS, cases with biological false positive reaction were examined. In ninety percent of patients with positive anti-thyroid antibody, thyroid antibody, thyroid diseases were demonstrated. However, various disorders were involved at the boundary levels of rheumatoid factor, antinuclear antibody, CH50 and serologic tests for syphilis. To assess the boundary levels of these serological data, it seems important to observe serial data and other clinical and laboratory findings. PMID- 8361030 TI - [An evaluation of tumor markers and risk factors in mass screening for various cancers]. AB - The borderline values of tumor markers and the clarification of risk factors for cancer are problems to be solved in the development of mass screening tests for various cancers. A tiny abnormality may be overlooked in an evaluation based upon traditional reference standards obtained by surveying healthy subjects. Both negative and positive values are required in mass screening for various cancers. That is, cut-off values should minimize the incidence of false negatives and false positives in the screening test. A modified combination assay using tumor markers and risk factors was used to screen 967 healthy subjects over age 50 for nonspecific cancers and the results were analyzed. Positive rates based on ordinary cut-off values for each tumor marker were about 6 to 7% in CEA, CA19-9 and BFP, 2.7% in SPAN-1, 1.3% in PAP, and less than 1% in AFP, SCC, CA125 and NCC -ST-439. For pepsinogen, a risk factor of various cancers especially in the digestive tract, the cut-off value was determined as the mean-SD in 967 healthy subjects over 50 years old. That is, the cut-of value for pepsinogen I was 18.7 ng/ml. A lower value was found in 149 subjects (15.4%). The cut-off value for pepsinogen II was 7.4 ng/ml and a lower value was found in 227 subjects (23.5%). The cut-off value for the pepsinogen I/II ratio was 1.2 and 108 subjects showed lower values (11.2%). Positive cases were referred to specialists in various fields to detect the specific suspected cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361031 TI - [Detection of carbohydrate antigens of malignant cells in sputum with panel of monoclonal antibodies]. AB - Serum tumor markers are useful for post-operative follow up, however, they are not necessarily useful for early stage diagnosis. Because the lesion is so small that it is unable to detect a tiny amount of their molecules in serum. If we could detect those antigens directly in cells from cytological specimens, it would provide a new diagnostic method for early stage cancers. The expression of carbohydrate antigens were examined with panel of specific anti-carbohydrate monoclonal antibodies (MAbs) on cytological specimens of sputum. In total, 146 sputa were collected in Sacomano's solution; 69 malignant cases (35 squamous cell carcinomas, 13 adenocarcinomas and 21 other primary lung cancers), 19 benign cases (pneumonia and bronchitis) and 58 borderline-malignancy cases which were defined by the standard of Japan Society of Lung Cancer. After removing mucus, the cells were stained with Vector's ABC method. Evaluation was performed by counting positively-stained cells among benign or atypical cells. As we examined previously in lung cancer tissue sections, there was statistical significance of frequency of positive stain between malignant and benign cases especially in MAbs AH6, THK2, SH1 and SNH3. Borderline malignancy gave intermediate value which means certain number of cells with cancerous biochemical character are mixed in the borderline specimens. In most cases, cell membrane was positively stained and sometimes, cytoplasm. Although the high sensitivity was observed in AH6 and SNH3, their specificity was lower than that of SH1, and visa versa. Those results indicate that the combination of anti-carbohydrate MAbs is useful for cytological diagnosis of lung cancer. PMID- 8361032 TI - [Magnet-supported chemiluminescent detection for amplified mecA gene of methicillin-resistant Staphylococcus aureus]. AB - A method of chemiluminescent detection for mecA gene of methicillin-resistant S. aureus amplified by polymerase chain reaction, was developed. The senseprimer was biotinylated at 5'-end, and an oligonucleotide probe, complementary to the senseprimer, was labeled with acridinium ester at 5'-end. Template DNA was obtained from colonies of S. aureus cultured on blood agar. Polymerase chain reaction product was hybridized with the probe and was separated using streptavidin-coated magnetic microparticles in magnetic field. The pellet was washed by decantations, and was measured for chemiluminescence in an automatic luminescence reader. For reference, drug sensitivity and presence of mecA gene were tested by dilution method and electrophoresis of polymerase chain reaction product, respectively, for each colony studied. Results showed that methicillin resistant S. aureus (n = 44) and methicillin-susceptible S. aureus (n = 19) can be successfully differentiated by chemiluminescence measurement. This method is specific, rapid, and suitable for handling a large number of samples. PMID- 8361033 TI - [Intestinal flora of inpatients and isolation frequency of methicillin-resistant Staphylococcus aureus]. AB - The authors compared intestinal flora from 30 healthy volunteers and 128 inpatients. E. coli, B. fragilis, and Bifidobacterium were each detected in the stools of healthy subjects at a frequency of more than 90%, while the incidences of such flora were low in the stools of inpatients: A significant difference was observed between the two groups. E. faecium, P. aeruginosa, Methicillin-resistant Staphylococcus aureus (MRSA), C. difficile, and Candida were detected at high frequencies in the stools of inpatients, as compared with healthy subjects. This finding is attributed to the administration of antimicrobial agents. It is also considered that microbial interaction in maintaining the balance among normal intestinal flora had been lost in patients from whom MRSA and/or C. difficile was isolated. The decrease or elimination of bacterial species antagonistic to such resistant strains must be guarded against, because this can lead to weakening of the defence mechanism against intestinal infection. PMID- 8361034 TI - [Serum superoxide dismutase (SOD) activity in diabetes mellitus]. AB - The serum superoxide dismutase (s-SOD) activities in patients with diabetes mellitus (DM) were assayed in order to evaluate its usefulness for monitoring of DM and also evaluate the relation between s-SOD activities and microangiopathies (nephropathy, neuropathy and retinopathy). As results followings were obtained; 1) s-SOD activities in DM patients were significantly higher than those in healthy controls (12.56 +/- 7.73 vs 10.51 +/- 1.69, p < 0.01). 2) There was no relations between s-SOD activities and FBS-, fructosamine- and HbA1-levels, respectively. 3) Among DM patients s-SOD activities were significantly higher in patients with microangiopathy than those in patients without microangiopathy (14.18 +/- 11.00 vs 11.24 +/- 3.13, p < 0.01). 4) Among DM patients with microangiopathy higher s-SOD activities tended to be observed in patients with triopathy such as nephropathy, neuropathy and retinopathy than in those with one or two microangiopathic complications. 5) Among DM patients with nephropathy the correlation was present between s-SOD activities and levels of creatinine. These results suggest that the assay of s-SOD activity is not useful for the monitoring of DM, however, it is suggested that the high s-SOD activity reflects the microangiopathic complications, particularly nephropathy. PMID- 8361035 TI - [Rapid alteration in serum lipoprotein profile after bile drainage in a patient with acute bile duct obstruction: contribution of cholestasis to cholesteryl ester-dominant ApoE-rich HDL accumulation]. AB - Remarkably increased cholesteryl ester-dominant apoE-rich HDL with alpha 2 mobility, similar to the apoE-rich HDL observed in primary biliary cirrhosis, was found in a patient with acute bile duct obstruction due to common bile duct carcinoma. Bile drainage rapidly lowered her serum apoE-rich HDL from 34.1 to 6.1 mg/dl and from 96 to 10 mg/dl in terms of apoE (control; 2.6 +/- 1.5 mg/dl, n = 38) and of cholesterol (control; 6.7 +/- 2.3 mg/dl, n = 38), respectively. Disturbance in hepatic lipoprotein clearance due to the presence of cholestasis without severe liver damage is a possible cause of accumulation of cholesteryl ester-dominant apoE-rich HDL. Hence, plasma cholesteryl ester-dominant apoE-rich HDL level is supposed to be a good indicator of hepatic lipoprotein clearance. The measurement of this lipoprotein and the analysis of its lipid composition, by our convenient method, would be useful for the diagnosis of cholestasis and for the evaluation of hepatic function in cholestatic patients. PMID- 8361036 TI - [Evaluation of serum protein fractions using nonlinear least squares method]. AB - We developed a method to evaluate the contents of serum protein fractions using nonlinear least squares approach. Parameters that determined the distributions of fractions of a densitogram were estimated assuming that each fraction obeys Gaussian distribution. One hundred test results of patients and one hundred and fourteen simulated patterns were analyzed with the proposed method and the traditional method. For patient data, the traditional method tended to give higher values in beta-globulin fraction and lower values in alpha 2-globulin and gamma-globulin fractions compared with our method. For the simulated data, the traditional method also tended to give higher values in beta-globulin fraction and lower values in gamma-globulin fraction, whereas our method gave the correct values. PMID- 8361038 TI - [Roles of pathology laboratories on medical care service and quality assessment system for pathological diagnosis]. AB - In practical medicine, pathologists provide highly specialized medical information (pathological diagnosis) to clinicians. Pathological diagnosis includes histopathology, cytology, intraoperative consultation (rapid diagnosis by frozen section) and autopsy service. In particular, histopathological diagnosis of biopsy specimens, nearly always gives a qualitative diagnosis to unknown pathological process, in other words, a final diagnosis. In addition, pathological diagnosis contributes to supporting medical audit. Thus it is quite important that to establish the quality assessment system for pathological diagnosis which is hard to be judged with the value. PMID- 8361037 TI - [Immunohistopathological analysis of estrogen receptors in human meningioma]. AB - We studied immunohistochemically estrogen receptors (ER) in 25 meningiomas removed from 20 patients using formalin-paraffin sections. Estrogen and progesterone receptors were studies in three case of meningiomas using frozen sections, also. Only two cases show positive reactions for estrogen receptor using formalin-paraffin sections. No correlation was found between estrogen receptor state and histological type, or biological behavior except for sex. Frozen sections failed to show the positive reaction for estrogen or progesterone receptors at all. The data suggest that estrogen receptors are detected in a few of the case with meningioma. Immunohistochemical analysis for estrogen receptor do not offer the useful informations in histopathological diagnosis or estimation of biological behaviors for meningioma on routine laboratory works. PMID- 8361039 TI - [Newly developed method by the use of factor Y assay for the detection of the lupus anticoagulant]. AB - A New method for the detection of lupus anticoagulant was developed. Plasma factor V activities using tissue thromboplastin (simplastin auto-SA) and partial thromboplastin (platelin excel LS-LS) were measured simultaneously. Furthermore, the ratio of the two activities was calculated (SA/LS ratio) as a marker of lupus anticoagulant. The normal range of SA/LS ratio was 0.79-1.39 (mean +/- 3SD). The high SA/LS ratios were detected in all of 15 patients with positive lupus anticoagulant, in 3 (5.8%) of 52 SLE patients with normal activated partial thromboplastin time, in 2 (28.7%) of 7 patients with hemophilia, in 1 (33.3%) of 3 patients with factor VIII inhibitor and in 4 (3.3%) of 122 patients with various diseases, respectively. All of 15 patients with liver dysfunction, 54 patients under warfarin treatment and 8 patients under heparin treatment had normal SA/LS ratio. PMID- 8361040 TI - [Studies on the fragments of FDP in 3 patients with DIC associated with acute promyelocytic leukemia]. AB - We previously reported a study on fibrinolysis and fibrinogenolysis that analyzed fragments of fibrin/fibrinogen degradation products (FDP) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In this report, we characterized the fragments of FDP in three patients with disseminated intravascular coagulation (DIC) associating with acute promyelocytic leukemia (APL). D, Y, DD, DY/X and high molecular weight fragments were observed in sera of all the patients obtained at the onset of APL. These results showed that various degrees of fibrinogenolysis, concomitant with fibrinolysis, was occurring in APL patients presenting DIC. However, changes in the patterns of the FDP fragments during anticoagulation therapy were apparently different among three patients. Namely, fibrinogenolysis was dominant in case 1, while fibrinolysis was dominant in case 2. Interestingly, fibrinogenolysis and fibrinolysis were almost equivalent from the onset to the end of DIC in case 3. In case 3, FDP and FDP-D dimer were remarkably elevated about two months before the onset of APL, although their elevation was not complicated with DIC but with bone marrow necrosis. At that time, serum LDH levels and plasma polymorphonuclear elastase (PMN-Ela) were increased presumably due to the release of these enzymes from necrotic bone marrow, and the levels of CRP and plasma fibrinogen were increased probably due to an infectious complication. In non-DIC period of case 3, FDP and FDP-D dimer were spontaneously decreased without reduction of PMN-Ela levels, after three weeks of chemotherapy for microbial agents. Taken together, characteristics of FDP fragments were unique to each case of APL-DIC, probably because many factors differently affected the degradation of fibrin and/or fibrinogen. PMID- 8361041 TI - [Final goal and problems in clinical chemistry examination measured by advanced analytical instruments]. AB - In the field of clinical chemistry of Japan, the automation of analytical instruments first appeared in the 1960's with the rapid developments in electronics industry. After a series of improvements and modifications in the past thirty years, these analytical instruments became excellent with multifunctions. From the results of these developments, it is now well recognized that automated analytical instruments are indispensable to manage the modern clinical Laboratory. On the other hand, these automated analytical instruments uncovered the various problems which had been hitherto undetected when the manually-operated instruments were used. For instances, the variation of commercially available standard solutions due to the lack of government control causes the different values obtained in institutions. In addition, there are many problems such as a shortage of medical technologists, a complication to handle the sampling and an increased labor costs. Furthermore, the inadequacies in maintenance activities cause the frequent erroneous reports of laboratory findings in spite of the latest and efficient analytical instruments equipped. Thus, the working process in clinical laboratory must be systematized to create the rapidity and the effectiveness. In the present report, we review the developmental history of automation system for analytical instruments, discuss the problems to create the effective clinical laboratory and explore the ways to deal with these emerging issues for the automation technology in clinical laboratory. PMID- 8361042 TI - [Immunoassay]. AB - Since the advent of radioimmunoassay in 1959, the immunoassay technology has developed enormously as a very sensitive assay system suitable for wide range of analytes of clinical interest. Current popularity of the noncompetitive principle is attributable to its higher sensitivity, wide dynamic range and shorter incubation time. Recent innovation includes time-resolved fluorescent immunoassay designed to eliminate non-specific fluorescence, amplified enzyme-linked immunoassay and enhanced chemiluminescent immunoassay for ultra-sensitivity, particle counting immunoassay with a high resolution power, simultaneous measurement of multiple analytes, and easy-to-perform multilayer film immunoassays. Despite these advances in the technology, there remain various assay problems such as lack of standardization in reagents, a large interlaboratory variations despite the use of same assay kits, non-linear results in diluted samples and so-called prozone phenomenon. PMID- 8361043 TI - [Blood coagulation-fibrinolysis tests by a biochemical method]. AB - Blood coagulation-fibrinolysis factors are conventionally measured using fibrinogen or fibrin as a natural substrate. With recent advances in the technology to biochemically separate and purify, individual coagulation fibrinolysis factors were isolated and purified, and their biochemical properties, function, and primary structure were clarified. Measurement techniques for blood coagulation-fibrinolysis factors were also developed. At present, enzyme activity for each factor is measured by the synthetic substrate method, on the other hand trace proteins and complex proteins are measured using monoclonal antibody. We present an outline of blood coagulation-fibrinolysis factors and synthetic substrates, and describe the characteristics of the synthetic substrate method using measurement of plasma tissue factor and protein C activity as examples. PMID- 8361044 TI - [Evaluation and problems of ultracentrifugal technique for separation and analysis of serum lipoproteins: comparison with other analytical methods]. AB - An ultracentrifugal technique for separating and analyzing serum lipoproteins was evaluated in comparison with analyses by electrophoresis using agarose-gel and polyacrylamide-gel. In general, the percent of pre beta- and beta-lipoproteins in electrophoresis was estimated higher than the percent of VLDL and LDL in ultracentrifugal method, while the percentage of alpha-lipoprotein in the former was estimated lower than that of HDL in the latter. In cases with abnormal lipoproteinemias, various discrepancies arose between the methods. For examples, pre beta- and beta-lipoproteins were estimated too high by the analyses with electrophoresis. The cholesterol content in HDL decreases in hypertriglyceridemia accompanied by an increase in triglyceride content. Therefore, when HDL cholesterol is determined by a polyanion method to assess the net HDL concentration in such cases, it is estimated to be low. Such errors are not only found in the determination of HDL cholesterol, but also in apoproteins in liver cirrhosis, because the composition of HDL apoprotein is markedly altered. Since the heterogeneity of lipoproteins separated by ultracentrifugation is characteristic in hereditary disorders of lipoproteins such as LCAT deficiency, the centrifugal technique is essential for lipoprotein analysis in such disorders. The disadvantages in ultracentrifugation are cross-contaminations among fractions, and removals of lipids and apoproteins from lipoprotein particles. Apo A-I and E proteins, and phospholipids were removed from the particles more rapidly than other components. From the results of repeated ultracentrifugation of HDL, 3% of apo A-I was estimated to be lost from the HDL during the centrifuge procedure. PMID- 8361045 TI - [Usefulness of admission biochemical tests for general medical patients]. AB - To evaluate the diagnostic utility of admission biochemical tests in the "Essential Laboratory Tests" proposed by the Japan Society of Clinical Pathology, we examined performance, abnormality and undetected abnormality in the tests of 250 randomly selected new patients admitted to the internal medicine wards of a prefectural general hospital during a year period. Each admission biochemical test was performed in 63% to 93% of the patients, and abnormal rates were obtained in 13% to 53% of each type of test performed. It is noteworthy that 37% of the patients were positive for HCV antibody and 32% had elevated blood glucose levels. In 28 of 250 patients, clinical diagnoses were supplemented or changed because of abnormal test results. However, in 15 cases, significant test results were overlooked. To promote appropriate action by the attending physician, we presented interpretative laboratory reports. Clinical usefulness of the reports was also evaluated. During the past four years, 100 interpretative biochemical test reports were accumulated. Diagnoses and treatments were supplemented or changed in 36 cases and 26 cases, respectively, because of the reports. In conclusion, effective and appropriate use of biochemical tests is promoted by interpretative reports. PMID- 8361046 TI - [Laboratory tests in primary care medicine: pre-clinical, ambulatory screening test system on the basis of the patient's chief complaints in the initial diagnosis making]. AB - We have explored the efficacious laboratory test system to be performed before the first medical contact with a physician on the basis of the patient's chief complaints and their abnormalities of the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology by analyzing 2,625 complaints from 2,175 new patients visited the outpatient unit of Comprehensive Medicine, National Defense Medical College. The patients with complaints such as general fatigue, fever of unknown origin or reno-urinary symptoms showed higher abnormalities of these diagnostic tests than those in 750 patients performed these tests irrespective of the patient's chief complaints. However, complaints originated from neurological, gastro-intestinal, cardiovascular or respiratory diseases were not associated with abnormalities of these laboratory tests in the patients as compared to those in 750 patients mentioned above. These results indicate that (1) clinical usefulness of the "essential laboratory tests" are variable depending on the patients chief complaints and these tests are recommended for the patients with complaints such as general fatigue, fever of unknown origin or reno-urinary symptoms as pre-clinical ambulatory screening tests before history taking and physical examination to enable to make accurate initial diagnosis and subsequent efficacious medical approach and (2) test items should be selected depending on the patient's chief complaints. PMID- 8361047 TI - [Detection of methicillin-resistant Staphylococcus aureus by in vitro enzymatic amplification of mecA and femA genes]. AB - In the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection, rapid detection of MRSA is extremely important. The mecA gene codes the new drug resistant polypeptides called penicillin-binding protein 2a (PBP2a) or 2'(PBP2'), which mediates the clinically relevant resistance to all beta-lactam antibiotics. This gene could be beneficial in the detection of MRSA using the polymerase chain reaction (PCR). However, the identical mecA gene has been found in both coagulase positive and coagulase-negative Staphylococcus with the appropriate methicillin resistant phenotype. The second gene related to the expression of methicillin resistance has been called femA. In this study, we amplified both mecA and femA genes by PCR in 97 strains and 32 clinical specimens. The mecA gene was positive in all 63(100%) MRSA strains and 2(6%) of the 34 methicillin-sensitive Staphylococcus aureus (MSSA) strains. Two strains with the methicillin-sensitive phenotype and the mecA gene resulted in methicillin-resistance when cultured on an agar plate containing 4.5% NaCl. The mecA gene was also present in all 10(100%) coagulase-negative Staphylococcus strains with the methicillin-resistant phenotype. The femA gene was positive in all 97(100%) MRSA and MSSA strains. On the other hand, the femA gene was absent from coagulase -negative Staphylococcus strains with the methicillin-resistant phenotype. Although the mechanism by which the product of femA gene influences the expression of methicillin-resistance is unknown, the gene appears to be restricted only in coagulase-positive Staphylococcus, regardless of methicillin-resistance. In conclusion, in vitro enzymatic amplification of both mecA and femA genes would lead to rapid and definite diagnosis of the MRSA infection. PMID- 8361048 TI - [Detection of alterations of dihydrofolate reductase gene in folate-resistant leukemia cells by in vitro enzymatic amplification]. AB - Three methods for analyzing the products of polymerase chain reaction were applied to detect complex alterations of dihydrofolate reductase (DHFR) gene, in order to assess their value in detection of folate-resistance in leukemia cells. A single point mutation in the second position of codon 31, a T-to-C transition, in trimetrexate (TMQ) resistant MOLT-3/TMQ200 cells was detected by either allele specific oligonucleotide hybridization or restriction pattern of the PCR product. These two analyses allowed us to detect not only the presence of the mutation, but also the amplification of the mutated gene in TMQ-methotrexate (MTX) doubly resistant MOLT-3/TMQ200-MTX500 cells. The base change was confirmed by direct sequencing method of the PCR product. Using these analyses of the PCR product, the complex alterations of DHFR gene are to be examined in leukemic patient cells. PMID- 8361049 TI - [Urinary-plasmin alpha 2 plasmin inhibitor complex (PIC) in patients with diabetic nephropathy]. AB - The levels of urinary PIC and FDP were studied in 86 diabetics. Urinary PIC or FDP were detected only in patients representing more than (++) urinary protein, suggesting that urinary PIC is not useful for diagnosis of early stage of diabetic nephropathy. On the other hand, positive rate of urinary PIC was much higher than that of chronic nephritis not due to diabetes mellitus. Plasma levels of PIC were elevated above normal range in all patients with advanced diabetic nephropathy tested. These results suggest that urinary PIC might be derived from circulating blood and reflect the level of systemic fibrinolytic activities in diabetics. PMID- 8361050 TI - [Iron deficient erythropoiesis in the young females--analysis by Percoll discontinuous density gradient]. AB - To observe changes in erythropoiesis in iron deficient subjects, we fractioned red cells by discontinuous density gradient using Percoll. Blood samples were taken from 57 young females of 19-21 years old without abnormal history or abnormal biochemical profiles except anemia or iron deficiency. 6 layers gradient were made and 7 fractions (F1 to F7, from the top to the bottom) were obtained. In the lightness fraction (F3 in nonanemic subjects), reticulocytes were concentrated. From patterns of Hemoglobin A1c concentrations of the fractions, it was inferred that red cells with heavier density were older in ages. In cases with iron deficiency or resulting anemia, low density fraction(s) increased in percentage, with relative decrease in that of higher density fractions, as a result of impairment in hemoglobin production. Subjects in whom the lowest density fraction (F3) was less than 5% were regarded to be normal in terms of erythropoiesis, because the fractional pattern was comparable to that of the normal adult males. Among 57 females examined, 24 (52.6%) showed iron deficient erythropoiesis and 6 (10.5%) were iron deficiency anemia (hemoglobin < 120 g/l). The density gradient fractionation of the red cells was proved to be useful in analyzing abnormal erythropoiesis. PMID- 8361051 TI - [Present status of computerization in routine pathology work in Japan: a questionnaire survey and its analysis]. AB - A total of 71.7% of the institutions surveyed were using computers, and most of the institutions not using computers were considering their introduction. Large computers were being used by 36% of the institutions and personal computers (PCs) by 61%. With regard to software, 88% of the large computers had been programmed by professionals, while 76% of the PCs were using commercially available software. The wide difference between the software used by the two types of computer makes it advisable to discuss them separately. The details on the patients at the stage of specimen registration was received on-line in 57% of institutions using large computers but in only 5.7% of those using PCs. Coding had been implemented in 47% of institutions using large computers and in 16% of those using PCs. The rate of use for case reference was 55% for large computers and 44% for PCs. References using a register as well as codes and letter data were also observed. It is considered that a wide-ranging method of reference will probably lead to better ideas than a scrupulous method. In the present survey, 59% of institutions using large computers and 35% of those using PCs replied that system improvements were troublesome. The only way to ensure the privacy of patients and the protection of pathological data is to enhance awareness among medical doctors and paramedical personnel. It is hoped that some organization will lead the way in collecting computer information on pathology duties and make this available free of charge. PMID- 8361052 TI - [Echocardiographic study in adult patients with Down's syndrome]. AB - In Down's syndrome (DS) mental retardation accompanying chromosomal abnormalities is seen, and the incidence of associated congenital heart abnormalities is also known to recent years, the accelerated aging and premature senility associated with DS have attracted attention. In the present study, we examined cardiac lesions using echocardiography in a group of asymptomatic adult DS subjects discussed the relation between these lesions and premature aging. The subjects comprised 28 adult DS patients ranging in age from 20 to 46 years (mean +/- SD, 30.8 +/- 8.9 years) residing in 8 institutions in Fukui prefecture. The presence of DS was confirmed in all cases by chromosomal examination, which revealed 21 trisomy in 25 and mosaic type in three. Of indices of left heart function, the end diastolic volume index (EDVI) and end systolic volume index (ESVI) showed significantly reduced values, whereas indices of systolic function such as the ejection fraction (EF) and mean velocity of circumferential fiber shortening (mean Vcf) showed significantly elevated values. The results of early diastolic left ventricular function, which has been noted to be related to aging, did not show any significant difference as determined by observation of mitral valve dynamics. On the other hand, morphologically, mitral valve prolapse (MVP) was found significantly more frequently in the DS group (17.9%) as compared to a normal control group. Also, valvular calcification (14.3%) and aortic valve regurgitation (AR, 11%) were both frequently noted. Whether signs such as valvular calcification are findings related to accelerated aging will require further study. PMID- 8361053 TI - [The correlation between changes in EEG and eye movement (EOG) accompanied by lowered arousal level]. AB - We investigated the correlation between the components of spontaneous eye movement (EOG) and EEG in six healthy individuals. The study was conducted in three periods; from the resting to drowsy stage, from the drowsy to spontaneous awakening stage, and in the forced waking stage. EEG, as registered from bipolar electrodes attached between the left parietal region (P3) and the left occipital region (O1), was monitored continuously by the FFT method with a segment of 12.8 seconds. Rapid eye movement and slow eye movement were observed simultaneously. In conclusion, even when the arousal level varies considerably, there is a close correlation between frequency of rapid eye movement and EEG patterns of 10.16 integral of 10.94 Hz & 17.97 integral of 19.53 Hz (simple correlation p < 0.01). Additionally, during the forced waking period (after stage 2), delta and theta bands increased in cases along with sleepiness. Even if the depth of sleep was the same, one's mood upon awakening was determined by the frequency of slow waves before awakening. PMID- 8361054 TI - [Effect of substrate and diluent for factor VIII activity in highly purified factor VIII concentrate and patient plasma infused factor VIII concentrate]. AB - We studied the difference between congenital factor VIII deficient plasma and factor VIII immuno-depleted plasma on the effect of pre-dilution for factor VIII activity determined by the one-stage assay. When standard curves of one-stage assay for factor VIII: C by GEORGE KING factor VIII deficient plasma (frozen at 80 degrees C), BEHRING factor VIII deficient plasma (lyophilized), DADE factor VIII depleted plasma (lyophilized, von Willebrand factor antigen 0.2 U/ml) and DADE factor VIII depleted plasma (lyophilized, von Willebrand factor antigen 1.0 U/ml) were compared, the difference between the clotting times for 100% and 6.25% of activity in each reagent were 39.5, 29.5, 25.0, 23.0 seconds respectively. Potency values in concentrates without albumin or von Willebrand factor showed a discrepancy between pre-dilution in Owren-Koller buffer and pre-dilution in factor VIII deficient plasma. Potencies of those products pre-diluted in Owren Koller buffer were 40-60% lower than potencies pre-diluted in factor VIII deficient plasma. These results showed substrate and pre-diluent must be chosen carefully for the accurate assay of factor VIII activity in vitro for the highly purified factor VIII concentrates. PMID- 8361055 TI - [The effects of exogenous and endogenous dopamine on the gastric microcirculation and their action sites in rat stomach]. AB - The effect of exogenous and endogenous dopamine on the gastric microcirculation and their action sites on stomach were investigated by laser Doppler flowmetry, histochemistry, electron microscopy and radioautography. The effects of graded doses of dopamine on the gastric mucosal blood flow were different from those on the systemic blood flow, implying that there may exist a dopaminergic control of gastric mucosal blood flow independent from the systemic circulation. By histochemical observations of the horseradish peroxidase (HRP) infused preparations, HRP was found to be distributed mainly to the arterioles and venules at the base of the gastric mucosa with a high dose of dopamine which may contributed to open the arterio-venular shunt either at the base of mucosa or in the submucosa. Pretreatment with monoamine oxidase inhibitor and/or 6 hydroxydopamine caused changes in the levels of endogenous catecholamine (dopamine, noradrenaline and adrenaline) in the stomach wall. An imbalanced catecholamine in the stomach wall, particularly an increase in DA, decreased gastric mucosal blood flow. Radioautographic studies revealed that D1-receptors are located mainly on the arterioles in the lower part of the mucosa and submucosa, while D2-receptors are located mainly on the muscularis mucosae and on the collecting venules. Tyrosine hydroxylase (TH) positive nerve fibers possibly corresponding to the dopaminergic fiber were evident in the vicinity to the arterioles, venules, and muscularis mucosae. Some TH-positive fibers were extended to the true capillaries in the mucosa. Dopamine beta-hydroxylase positive fibers were noted near the arterioles and venules both in the submucosa and the lower portion of mucosal layer. Based on the above results, the dopaminergic mechanisms are considered to be involved in the regulation of the gastric mucosal microcirculation through the dopaminergic nerves. PMID- 8361056 TI - [Changes in gastric mucosal glycosidases and thiobarbituric acid reactants induced by burn stress in obstructive jaundice rats]. AB - To elucidate the pathogenesis of acute gastric mucosal lesion (AGML), burn stress was loaded in rats with and without obstructive jaundice. The activation of gastric mucosal glycosidases (beta-N-acetyl-D-glucosaminidase (NAG), beta glucuronidase (BG)), which were released into the cytoplasm as a results of instability of the lysosomal membrane, was studied biochemically, enzymatically and histochemically after burn stress with and without obstructive jaundice. The latent enzyme activity calculated by NAG or BG, which represented the stability of lysosomal membrane, was lowest at 2-3 hour after burn stress in both groups. In other words, the degree of activation of the glycosidases was highest at 2-3 hour after burn stress. The latent enzyme activity calculated by NAG decreased significantly (p < 0.05) at 1 hour after burn stress in obstructive jaundice group compared with the non-obstructive jaundice group. The staining of NAG before burn stress was observed in mucus neck cell and surface epithelial cell in granular shape and it was observed diffusely after burn stress, especially in obstructive jaundice group. The changes in staining of BG was similar to NAG. Before activation of glycosidases, the thiobarbituric acid reactants, which are considered products of lipid peroxidation, increased promptly at 30 min after burn stress in both groups. Ulcer index increased gradually after burn stress and the significance was found between in the obstructive jaundice group and in non obstructive jaundice group at 3 hour after burn stress. It's concluded that obstructive jaundice accelerated the fragility of lysosomal membrane after burn stress and these change were considered to be the reasons of frequent occurrence of AGML. PMID- 8361057 TI - [Newly developed ultrasonic micro-probe (15MHz), basic and clinical study for gastrointestinal lesions]. AB - The authors evaluated a new device the ultrasonic micro-probe (2.4mm in the outer diameter, radial scanning system, 15MHz, Toshiba Co.) from both its basic and clinical aspects using resected gastric specimens and clinical subjects. The ultrasonic resolution of this new ultrasound imaging catheter was demonstrated to be best the probe-object distance was 1.0-3.0mm and angle of inclination was 0 20. On clinical use of the probe, the above-mentioned basic evaluation is important to achieve high resolution ultrasonic image. For attenuation of ultrasound due to the high-frequency (15MHz), the main subjects of this probe for evaluation of gastrointestinal tract are small lesions of mucosal-submucosal layers. Because of its small caliber (2.4mm), the micro-probe can be passed through the biopsy channel of common used endoscope, and permits the intra luminal ultrasound examination at routine endoscopy, if necessary. This new device the ultrasonic micro-probe will develop the ability of endoscopic ultrasound in diagnosing gastrointestinal disorders. PMID- 8361058 TI - [Development of colonic lesions caused by occlusion of paracolic marginal artery and/or vein--an experimental study using the model of ischemic colitis]. AB - Paracolic marginal artery and/or vein of rabbit descending colon were ligated at two points with a distance of 3cm each other. The animals were sacrificed 1, 4 and 7 days after the operative procedure. The colonic segment including the vessel-ligated region was removed and studied macroscopically and microscopically. The impairment of arterial blood supply was more responsible for the development of colonic lesions. Especially, ulcerative lesions occurred only in artery-ligated and both of artery and vein-ligated groups. All the lesions occurred in the vein-ligated group were those showing only edema. Three types of mucosal folds with different etiology appeared in the vessel-ligated region of the colon, i. e., longitudinal and transverse folds and those converging to the ulcerative lesion. The morphological features of colonic lesions changed gradually. In the artery-ligated group, a variety of lesions including multiple ulcers and petechiae appeared with a longer lapse of time. PMID- 8361059 TI - [Detection of obscure fistulas complicated with Crohn's disease by indocyanine green]. AB - When treating patients with Crohn's disease (CD), external or internal fistulas connected to the intestine were encountered, and these were often difficult to diagnose correctly. In order to diagnose such fine fistulas, we modified a method of using indocyanine green (ICG) administration to the gut lumen. The subjects of this study comprised nine patients with CD who had an obscure fistula which could not be demonstrated by barium study, fistulography, or by urological or gynecological examinations. If the administrated ICG was detected by various ways from an external fistula or from the neighboring organs, a fistulous connection was thought to be evident. Following oral administration in nine patients, colonic fistulas became evident in seven and by ICG enema in three patients, colonic fistulas became evident in all three. In addition, since the fistulous connection was ameliorated following nutritional therapy, it would appear that ICG administration is a useful marker of such therapy for this condition. ICG administration was therefore thought to be a useful method of detecting obscure fistulas connected to the intestine. PMID- 8361060 TI - [A study of osteopenia in liver cirrhosis by dual energy X-ray absorptiometry (DXA)]. AB - We studied osteopenia in patients with liver cirrhosis by dual energy X-ray absorptiometry (DXA). Total body bone mineral density showed a positive correlation with the lumbar spine bone mineral density, and % age matched total body bone mineral density under 90% was defined as osteopenia. The incidence of osteopenia in 54 patients with liver cirrhosis was 20.4%. Since this osteopenia had no relationship to the general risk factors for osteoporosis, it was suggested that it is a complication specific to liver cirrhosis. Because the level of serum total bilirubin and the activity of serum total alkaline phosphatase in the group with osteopenia were usually higher than those in the group without osteopenia, it was suggested that osteopenia in liver cirrhosis might be related to hepatic dysfunction. PMID- 8361061 TI - [Gastroduodenal Crohn's disease: report of a case and review of Japanese literatures]. PMID- 8361062 TI - [A case of surreptitious laxative abuse diagnosed by high performance liquid chromatography]. PMID- 8361063 TI - [Acute hepatic failure after complete remission of the hematopoietic malignancy]. PMID- 8361064 TI - [The relationship between aortic pulse wave velocity and atherogenic index in centenarians]. AB - It is considered that the atherogenic index (AI), calculated from cholesterol fraction levels, is biochemically acceptable but cannot completely express the degree of physiological development of individual arteriosclerotic changes in extremely elderly persons. The purpose of this study is to search for another form of the atherosclerotic index which is more reliable in terms of physiological aspects, and to clarify the relationship between aortic pulse wave velocity (PWV) and AI in centenarians. We have measured the PWV in 40 healthy centenarians (7 males and 33 females; age 100 to 105, average age 101.1) and 92 ordinary elderly people (45 males and 47 females; age 70 to 89, average age 75.8) in Okinawa, Japan. The conventional AI was calculated by the Fridewald Method. A statistically significant difference in the AI value was observed between centenarians (1.91), and controls (2.59, p < 0.0001). Higher levels of PWV in centenarians (10.15 m/sec), were recognized than in the controls (8.45 m/sec, p < 0.0001). However, no significant correlations were noticed between PWV and AI in centenarians (r = 0.0049) and in controls (r = 0.094). These results suggested that pathological findings in centenarians are produced mainly by physiological fibrotic changes of the arterial wall instead of pathological atherosclerotic changes. PMID- 8361066 TI - [Three cases of acquired megacolon in the elderly]. AB - As the number of the elderly in society increase, cases of abnormal bowel habit in the aged have also increased. This report describes 3 cases of acquired megacolon in the elderly. Case 1, a 71-year-old female, complained of constipation and developed megacolon after an attack of cerebral infarction. Case 2, a 82-year-old male, developed megacolon while receiving psychoactive medication. Case 3, a 69-year-old male who complained of constipation for a long time and rapidly developed megacolon was diagnosed as idiopathic megacolon. PMID- 8361065 TI - [The importance of the host nutritional and immune status on the prognosis of urinary tract infection in the elderly]. AB - This study was performed to evaluate the role of the nutritional and immune status on the prognosis of urinary tract infections (UTI) in the elderly. 192 patients among the 790 inpatients were diagnosed as UTI. Age-related increase in the prevalence of UTI was accompanied with poor prognosis in the patients with hypoalbuminemia (< 2.6 g/dl) and lymphocytopenia (< 700/mm3). To study the immunologic basis for susceptibility to UTI in the aged further, we compared the T-cell functions between outpatients without serious disease and inpatients with chronic UTI. The absolute numbers of lymphocyte, OKT3 (pan T-cell marker), OKT4 (Helper/Inducer marker) and Interleukin (IL)-2 as well as serum albumin concentration were decreased in the patients with UTI. A prospective study was done to confirm that these nutritional and immunological changes become risk factors in the prognosis of UTI with long-term and low-dose chemotherapy. In the patients continued with bacteriuria (Non-responders, n = 6), serum albumin concentration and IL-2 production were significantly lower than the patients who became free from bacteriuria (Responders, n = 7). These results suggest that poor nutrition-related immune dysfunction contributes to the vulnerability of elderly patients to UTI and becomes risks for he prognosis of UTI. PMID- 8361067 TI - [Two cases of Werner's syndrome treated with penetrating keratoplasty]. AB - Cataract is one of the typical ocular manifestations of Werner's syndrome. In contrast to cataract in normal elderly persons, cataract in patients with Werner's syndrome is known to be associated with degenerative corneal changes after cataract surgery. Among the corneal changes bullous keratopathy occurs in almost 100% of patients with Werner's syndrome after cataract surgery. Although penetrating keratoplasty appears to be the best treatment for bullous keratopathy, there have been few reports on bullous keratopathy in patients with Werner's syndrome. Here we report two patients with Werner's syndrome who underwent penetrating keratoplasty for the treatment of bullous keratopathy. In both cases, visual acuity was improved, suggesting that penetrating keratoplasty is a recommendable treatment for bullous keratopathy in patients with Werner's syndrome. PMID- 8361068 TI - [Non-Hodgkin's lymphoma with pulmonary involvement and various immunological abnormalities in an elderly patient]. AB - A 85-year-old female was admitted with general fatigue and chest discomfort in July 1991. Her chest X-ray film showed several pulmonary nodules in the bilateral lung fields without hilar lymphadenopathy. Metastatic lung cancer was suspected, but primary cancer was not detected in spite of cancer screening. Hemoglobin was 8.7 g/dl. The patient also had various immunological abnormalities including increased serum cold agglutinin titer, decreased serum complement, positive anti nuclear antigen and IgM-kappa monoclonal gammopathy detected by immunoelectrophoresis. She was diagnosed as having autoimmune hemolytic anemia with cold agglutinin disease and M-protein. With the administration of corticosteroids, hemolytic anemia improved temporarily, but the patient died of hemorrhagic gastritis. At autopsy, a lung tumor was detected in the left upper lobe, mainly without hilar lymphadenopathy. The autopsy specimens showed Non Hodgkin's lymphoma (diffuse medium-sized cell type), differentiated from macroglobulinemia by immunohistochemical studies. In elderly patients, with various immunological abnormalities, B-cell lymphoproliferative disorders such as malignant lymphoma should be suspected. PMID- 8361069 TI - [Age difference in appearance of synaptophysin positive substance of rat hippocampus--immunohistochemical study]. PMID- 8361070 TI - [Rehabilitation for the elderly with hip fracture. From onset to terminal stage]. PMID- 8361071 TI - [Energy metabolism and nutrition in the elderly]. PMID- 8361072 TI - [Energy requirements for frail elderly females]. AB - About half the residents living in nursing homes and homes for the elderly show activity factor values less than 0.25 in daily living. However, the current Recommended Dietary Allowances (RDA) have been intended to apply to self supporting and healthy elderly persons rather than bedridden elderly persons. Accordingly, current RDA tables do not indicate energy requirements for frail elderly people who show less values than 0.25 in activity factor. Consequently, in most institutions for the elderly, an adequate dietary energy supply for residents has been calculated on the basis of "level I (light)" in levels of physical activities. In this study, we measured the daily energy expenditures of 78 frail elderly females (age; 79.9 +/- 7.1 yrs) living in nursing homes and homes for the elderly. From these results, energy requirements for frail elderly females corresponding with 0.00 to 0.25 of the activity factor were provisionally estimated as to be 21 to 31 kcal/kg BW. PMID- 8361073 TI - [Aging, basal metabolic rate, and nutrition]. AB - Age is one of the most important factor of changes in energy metabolism. The basal metabolic rate decreases almost linearly with age. Skeletal musculature is a fundamental organ that consumes the largest part of energy in the normal human body. The total volume of skeletal muscle can be estimated by 24-hours creatinine excretion. The volume of skeletal musculature decreases and the percentage of fat tissue increases with age. It is shown that the decrease in muscle mass relative to total body may be wholly responsible for the age-related decreases in basal metabolic rate. Energy consumption by physical activity also decreases with atrophic changes of skeletal muscle. Thus, energy requirement in the elderly decreases. With decrease of energy intake, intake of essential nutrients also decreases. If energy intake, on the other hand, exceeds individual energy needs, fat accumulates in the body. Body fat tends to accumulate in the abdomen in the elderly. Fat tissue in the abdominal cavity is connected directly with the liver through portal vein. Accumulation of abdominal fat causes disturbance in glucose and lipid metabolism. It is shown that glucose tolerance decreases with age. Although age contributes independently to the deterioration in glucose tolerance, the decrease in glucose tolerance may be partly prevented through changes of life style variables, energy metabolism is essential for the physiological functions. It may also be possible to delay the aging process of various physiological functions by change of dietary habits, stopping smoking, and physical activity. PMID- 8361074 TI - [Physical fitness and energy metabolism of the elderly]. AB - It is generally accepted that decreased lean body mass (LBM) with aging is responsible for decline in basal metabolism (BMR) of the elderly. However, multiple regression analysis of BMR and related factors for middle- to older-aged subjects showed that decline in BMR with aging could not be explained only by decrease in LBM. Basal heat production rates per essential body mass (EBM) and per fat tissue mass (FTM) by sex and by age class were estimated using the regression analysis proposed by Chirifu. It was found that the basal heat production per EBM decreased with aging, indicating that both decreases in active tissue mass and BMR per unit of active tissue mass were involved in reduced BMR for the elderly. A 15-week aerobic exercise training course prescribed for mildly obese middle- to older-aged women improved their fitness level and body composition, i.e., decrease in FTM with increase in EBM. The basal heat production rate per EBM increased by 21%. These results suggest that aerobic exercise training is effective for improving the metabolism of active tissue in the middle-aged and the elderly. Although there was a wide inter-individual variation in BMR in the elderly over 70 years of age, the BMR tended to increase depending on the level of daily activity. In conclusion, physical exercise and an active daily life are important for decelerating the decrease in BMR for the elderly through maintaining active tissue mass and its basal metabolism. PMID- 8361075 TI - [Relation of habitual exercise to basal metabolic rate and energy expenditure during exercise in older people]. AB - The relation between habitual exercise and the basal metabolic rate, energy expenditure during exercise (lactic threshold and maximal oxygen uptake) was examined in 291 older people. Metabolic rate was highest in old players of gatebowl (a form of croquet) (male; 23.3 +/- 2.3, female; 22.7 +/- 3.0 kcal/kg/day), higher in old untrained people (male; 21.9 +/- 2.5, female; 20.8 +/ 2.4 kcal/kg/day), and lower in old people in a home for the aged (male; 20.6 +/- 3.5, female; 20.8 +/- 3.7 kcal/kg/day). Energy expenditure while walking at a speed of less than 100 m/min was similar in trained and untrained old people aged 60-69 years. However, lactic threshold was higher in trained (30.2 +/- 4.8 ml/kg/min) than in untrained (20.9 +/- 2.8 ml/kg/min) females aged 60-69 years. Maximal oxygen uptake was higher in trained (male; 50.4 +/- 4.1, female; 36.6 +/- 3.9) than in untrained (male; 30.9 +/- 3.7, female; 26.8 +/- 2.8) old people aged 60-69 years. It was suggested that a higher basal metabolic rate, lactic threshold and maximal oxygen uptake resulted in higher daily physical activity and larger daily energy consumption in trained old people. PMID- 8361076 TI - [Nutritional assessment and nutritional support therapy in elderly patients]. AB - In order to study nutritional assessment and nutritional support therapy for elderly patients, we conducted energy supply therapy on 15 elderly (aged over 75) patients disabled with diseases such as cerebrovascular disease, pneumonia and heart failure. After recovery from acute phase, they were divided into 3 groups, and assigned to 3 different energy supply methods for 2 weeks: Six (3 males, 3 females) could take hospital diet, but only could absorb about 50% of the energy, amounting only 1,000 to 1,400 kcal/day. Additional 246 kcal was given by peripheral parental nutrition (PPN). Five (2 males, 3 females) were unable to take nutrition orally. Therefore, they were given high caloric nutrients by total parental nutrition (TPN), giving (1,222 kcal daily for a week), then 1,666 kcal for another week. Four (1 male, 3 females) also could not take meals orally, and had to be nourished by enteral nutrition (EN) with a nutrient preparation of 1,120 kcal for one week, then with 1,600 kcal for another week. In all 3 groups, the indices of rapid turnover proteins (pre-albumin, retinol binding protein and transferrin), choline esterase and vitamin A significantly elevated after 2 weeks of therapy, though the increase of pre-albumin and RBP in TPN group was slightly below the significant level. The increase in rapid turnover proteins and choline esterase was greater in the order of EN, TPN and PPN. Vitamin C, on the other hand, decreased significantly with treatment in all the groups, while vitamin E remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361078 TI - [Factors for weight loss in patients with senile dementia]. AB - The authors investigated causes for weight loss in inpatients with senile dementia, who could take diets. The 81 patients (80 +/- 8.3 years of mean age +/- S.D., 22 males and 59 females) included 48 cases of senile dementia of Alzheimer type (SDAT) and 25 cases of multi-infarct dementia (MID). Controls consisted of 77 non-demented patients (82 +/- 9.1 years, 29 males and 48 females) who were admitted because of cerebrovascular or cardiopulmonary diseases. Demented patients showed an average of -1.8 +/- 8.5% weight change per year, while that of non-demented patients was +4.4 +/- 6.3%, resulting in a significant difference between them (p < 0.0001). Between demented males and females, there was no significant difference. In male, SDAT cases showed more weight loss than MID cases (-5.0 +/- 5.1% vs +3.3 +/- 4.2%, P = 0.003), although in females there was no significant difference between SDAT and MID. Even when patients with a wandering tendency or complications were excluded, results essentially did not change. In demented patients, weight change did not correlated with age, amount of dietary intake, length of hospital stay or serum albumin level. However, it correlated with body weight (r = 0.26, P = 0.014), ADL index (GBS-A) (r = 0.22, P = 0.04), and with Mini-Mental State Examination score (r = 0.23, P = 0.048). In multiple regression analysis, the most powerful explanatory variable in demented males was the index for cerebral atrophy. These results confirmed previous studies reporting that reduced dietary intake, complications or hyperactivity do not fully explain weight loss in demented patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361077 TI - [Hyperinsulinemia and hypertension in an elderly Japanese population--the Hisayama Study]. AB - Hyperinsulinemia has been closely associated with hypertension in several epidemiological studies, but little is known about this condition in the elderly. The authors studied the relationship between serum insulin and blood pressure levels, and the prevalence of hypertension according to insulin levels in the elderly in a Japanese rural community, Hisayama. In 1988, 75 g oral glucose tolerance test was performed on 426 male and 567 female Hisayama residents aged 60 to 79 years. Fasting and 2 hr serum insulin values were measured by radioimmunoassay. In the subjects, excluding those receiving antihypertensive drugs, the sum of fasting and 2 hr postload insulin (sigma IRI) significantly correlated with systolic (r = 0.15 and 0.25 for males and females, respectively) and diastolic blood pressure (r = 0.20, 0.16). In multiple regression analyses, the correlation with systolic blood pressure remained significant in females after controlling for age, body mass index, alcohol intake, smoking habits, serum total cholesterol, HDL-cholesterol, triglycerides, and fasting plasma glucose. In contrast, sigma IRI did not remain as an independent variable relevant to blood pressure among males. The age-adjusted prevalence rates of hypertension (> or = 160/95 mmHg or receiving drug treatment) significantly increased with increasing quartiles of sigma IRI in females. The prevalence of hypertension which was not treated with drugs also increased significantly with increasing sigma IRI in females. However, no significant association was observed in males. In conclusion, the present study suggests that hyperinsulinemia can be related to hypertension in the female elderly in the general population of Japan. PMID- 8361079 TI - [Age-related changes in intracranial artery velocity measured by transcranial Doppler sonography in normotensive, hypertensive and diabetic patients]. AB - We measured mean blood flow velocity (MFV) and Fourier pulsatility index (PI) of the M1 portion of the middle cerebral artery (MCA) by transcranial Doppler mapping technique (2 MHz, Trans-scan, EME Co., Ltd.). The correlations between these parameters and arteriosclerotic risk factors such as aging, hypertension and diabetes mellitus were examined. Healthy volunteers as well as patients suffering from hypertension and diabetes mellitus were studied. A total of 59 persons (85 MCAs) consisting of 30 males (mean age 54.4, 24-81 years) and 29 females (mean age 54.8, 20-75 years) were enrolled in this study. Some hypertensive or diabetic subjects had previous cerebrovascular disease, therefore cases who had only minor stroke or asymptomatic infarction without significant lesions in carotid artery system were included. After excluding brain embolism, these subjects were divided into three groups as normotensive/non diabetic group (NT/non DM), hypertensive group (HT) and diabetic group (DM). In each group, MFV decreased with aging, being more evident in the HT and DM groups than in the NT/non DM group. Fourier PI also showed a significant increase with aging, and the correlation was stronger than that between MFV and age. Moreover, these trends of age-Fourier PI relationship were more highly significant in HT and DM groups than NT/non DM group. In cases with HT or DM, age-related arterial changes appeared to be more severe than in those without. Fourier PI seemed valuable for detecting arterial lesions with aging, HT and DM. PMID- 8361080 TI - [Analysis by two-dimensional electrophoresis of the cause of myocardial dysfunction in aging rat hearts]. AB - The severity and frequency of atherosclerosis, diabetes, and ischemic heart disease, which affect cardiac function, increase with aging. Although there are many reports about hemodynamic and histopathological studies about aging hearts, there are very few studies on changes in structural proteins in aging hearts. We investigated the contractile proteins of the left ventricles in rats aged 6, 12 and 125 weeks using two-dimensional electrophoresis. There were no difference in structural proteins in heart between 6-week and 12-week-old rats. The contents of myosin heavy chain, myosin light chain 2, actin, troponin-I in 125-week-old rats decreased compared with those of 12-week-old rats. Myosin heavy chain, which is one component of myosin, interacts with actin and changes chemical energy to mechanical energy. Therefore its decrease leads to a decline in myocardial contractility. These results seem to indicate one of the most important changes in the aging rat heart, as well as impairment in relaxation by the increase of interstitial fibrosis and decline of Ca uptake by sarcoplasmic reticulum. PMID- 8361081 TI - [The effect on age for the relationship between hypertension and glucose intolerance]. AB - Recently, high frequencies of glucose intolerance and insulin resistance have been reported in patients with hypertension. However, both blood pressure and glucose tolerance are influenced by age. To investigate the effect of age on the interaction between blood pressure and glucose tolerance, we analyzed blood pressure and glucose tolerance in otherwise healthy subjects (n = 576) who underwent an oral glucose tolerance test and blood pressure measurement as a part of a healthy care program. The prevalence of DM and IGT were significantly higher in the hypertensive group than in the normotensive group. When the subjects were divided into three groups according to their age (less than 50 years old, between 50 and 60 years old and more than 60 years old), the prevalence of glucose intolerance (DM or IGT) was significantly higher in the hypertensive group than in the normotensive group in subjects under 50 years old, but not in subjects between 50 and 60 years old or over 60 years old. In the subjects classified as having normal glucose tolerance, the incremental area of glucose under the curve of 75g-OGTT was significantly higher in the hypertensive group than in the normotensive group. These data suggest that hypertension is associated with glucose intolerance in Japanese population and that age significantly affects this interaction. PMID- 8361082 TI - [Two elderly cases of megacolon associated with cerebral infarction and diabetes mellitus]. AB - The authors experienced two elderly patients of megacolon associated with cerebral infarction and diabetes mellitus. The first patient was a 66-year-old female who was admitted to our hospital for rehabilitation with a complaint of knee pain. She had suffered from diabetes mellitus since she was 30 years old and multiple cerebral infarction since age 62. Two months after admission, she had an episode of abdominal distension and obstructive symptoms. The roentgenograms of her abdomen showed diffuse dilatation of the colon. The second patient was a 78 year-old female admitted to our hospital with complaints of abdominal pain, distension of the abdomen and vomiting. Her abdomen was severely distended and plain roentgenograms of the abdomen, X-ray studies of the colon with the aid of contrast medium and CT scan of the abdomen showed striking dilatation of the colon. Megacolon may be congenital or acquired, and in acquired forms the conditions are secondary to organic diseases, smooth muscle atrophy, metabolic and neurological diseases, ulcerative colitis or psychogenic origin (idiopathic). The two patients in this series were suffered from cerebral infarction and diabetes mellitus. The mechanisms of megacolon seen in these two patients are not known, but involvement of the visceral autonomic innervation is presumed. Some elderly patients have chronic constipation, and dilatation of the colon may not be uncommon due to underlying diseases or drugs. Therefore, when examining elderly patients, careful attention should be paid to their bowel movement. PMID- 8361084 TI - [Immune reaction, inflammation and sclerosis]. PMID- 8361083 TI - Angiotensin II receptors: cloning, structure, function and regulation. PMID- 8361085 TI - [Dialysis therapy--1992]. PMID- 8361086 TI - [Renal transplantation--1992]. PMID- 8361087 TI - [Nutrition and renal disease]. PMID- 8361088 TI - [The role of the kidney in essential hypertension]. PMID- 8361090 TI - [Pregnancy induced hypertension and renal changes]. PMID- 8361089 TI - [The histopathology of tubulo-interstitial nephritis]. PMID- 8361091 TI - [Mesangial cells and growth factors]. PMID- 8361092 TI - [Clinical and basic studies on immunosuppressive agents in renal disease]. PMID- 8361093 TI - [Studies in Walter-electrolyte metabolism on the basis of molecular biology]. PMID- 8361094 TI - [Gene expression for extracellular matrix components and growth factors in DBA/2FG-pcy mice with polycystic kidney disease]. PMID- 8361095 TI - [The experimental models of glomerulonephritis--the present status and the prospect for the future]. PMID- 8361096 TI - [Recent advances in the research on the acute renal failure--pathophysiological aspect]. PMID- 8361097 TI - [Surgical treatment of elderly patients with primary lung cancer]. AB - Fourteen patients with lung cancer over the age of 70 years had the standard operation with mediastinal lymph node dissection. Their postoperative complications and prognoses were compared with those of 47 patients under the age of 70 years with the same operation. The propriety of the standard operation with mediastinal lymph node dissection for lung cancer in elderly patients was studied. A program of respiratory training was arranged preoperatively for the patients. Preoperative complications was more common in elderly than in younger patients, but postoperative complications were less frequent. The prognosis in elderly patients was also satisfactory. We conclude that the standard operation with mediastinal lymph node dissection for lung cancer can be performed as well in elderly as in younger patients. PMID- 8361098 TI - [A role of valvuloplasty in surgical treatment of isolated tricuspid regurgitation]. AB - Seven surgical cases of isolated tricuspid regurgitation were reviewed. From pathological point of view, the patients were classified into three groups. Two were due to abnormalities of subvalvular system, four to annular dilatation and one to anomalous leaflet. Among four cases of annular dilatation, two were diagnosed as dilated cardiomyopathy. In one, it was very rare myopathy confined to right ventricle. Three cases, two subvalvular and one leaflet abnormalities, underwent valvuloplasty which included chordal reconstruction using Gore-Tex suture. Among annular dilatation group, three underwent valve replacement (two with mechanical valve and one with bioprosthetic valve), while fourth underwent annuloplasty. When We look at 89 surgical patients with secondary tricuspid regurgitation, thrombosed mechanical valve was seen in two cases, one of them necessitating re-valve replacement. On the other hand, late results of tricuspid annuloplasty with Carpentier-Edwards ring was excellent without re-operation. Although isolated tricuspid regurgitation has very complicated pathological features, we now think it very important to manage to repair regurgitant tricuspid valve utilizing all available techniques including redundant valve tissue resection, chordal reconstruction, and annuloplasty, thus avoiding valve replacement especially with mechanical valve. PMID- 8361099 TI - [Tracheobronchial injury: clinical analysis of 17 consecutive cases]. AB - Consecutive 17 tracheobronchial injury caused by blunt chest trauma were reviewed. 14 patients were injured by traffic accidents, 2 by fall from the high, and one by accident during play in the house. 16 were male and one was female. Patient's age range from 4 to 60 years (average 25). Site of tracheobronchial injuries were scattered and there were not found risky area. Several problem to rescue tracheobronchial injuries are discussed. To maintain the ventilation in the patient of carinal injury, it is supposed that jet ventilation may be a possible method. For the infant victims, it is difficult to evaluate the injury using bronchofiberscopy. It is recommended that repair of tracheobronchial injury may be undergone as soon as the general condition becomes enough for anesthesia. On a technical aspect, stay suture should be put at the healthy site because those injuries are larger than expected before operation. For the victims with cerebral injury or shock, respirator is necessary for ventilatory management. In those cases adequate sedation and muscle relaxation should be applied. PMID- 8361100 TI - [Disadvantages of "Gelseal graft" as a vascular prosthesis]. AB - In clinical use, the Gelseal Triaxial graft have been shown to have several problems, such as pyrexia, pleural effusion and seroma formation around the graft. To investigate the cause of these complications, we examined mechanical and biological properties of the graft. The water permeability was found to be 0 ml at 120 mmHg in an in vitro study. Scanning electron microscopical observation revealed that gelatin in the graft wall was not uniform and easily detached from the luminal surface. The amount of impregnated gelatin in the graft was found to be 6.73 mg/cm2. In addition, this graft contained 297 and 73 pg endotoxin in extract/g of graft wt at 25 degrees C 72 hrs as assessed by Toxicolor and Endospecy pyrogen tests, respectively. The grafts were implanted in the descending aorta of 8 dogs for 2 weeks in an animal study. Three out of 8 animals died of graft occlusion. Both macroscopic and microscopic evaluations of the explants from 5 dogs showed that neither fibroblasts nor capillary blood vessels had infiltrated in some area of the graft wall. Serous fluid was found to be retained between the graft and the surrounding host tissue in three cases. These results indicated that the Gelseal graft was easy to implant due to zero porosity, but the coated gelatin was not clean and gelatin was easily detachable. Hence, the graft would be prone to some complications such as pyrexia, immune response, thromboembolism, seroma, and pleural effusion. One must be aware of the potential disadvantages of the Gelseal grafts before using it in patients. PMID- 8361101 TI - [Newly-developed catheter for cardio-renal assist during intraaortic balloon counterpulsation]. AB - A new catheter was developed for the cardio-renal assist during intra-aortic balloon counterpulsation. The catheter consists of both a large balloon of conventional IAB (TMP balloon) located at the distal end of the catheter and an additional small balloon 10 cm distant from the large balloon with common lumen and single shaft. Experimental study was carried out in the mock circulatory system simulating the descending aorta employing a conventional IAB catheter as a control. It was demonstrated that the flow in the mid portion between both balloons could be increased maximally by as much as 28% of that of the control under the continuous flow and 214% under the pulsatile flow. The double balloon catheter was considered to improve the renal perfusion as well as the coronary perfusion. PMID- 8361102 TI - [A successful insertion of the prosthetic valve in supraannular position concomitant with pericardial enlargement of the aortic root in a child: a case report]. AB - A 4-year-old boy admitted to our hospital due to congestive heart failure one year after the intracardiac repair of tetralogy of Fallot. Echocardiography and cineangiography revealed severe aortic regurgitation. The aortic valve replacement was performed with a prosthesis larger than the aortic annulus. Operative findings showed that the cause of aortic regurgitation was infective endocarditis. The aortic root was enlarged with pericardial patch and a 21 mm St. Jude Medical valve prosthesis was inserted in supraannular position. This technique was very useful for insertion of a prosthetic valve one or two sizes larger than the aortic annulus without risk of distorting the mitral valve or left ventricular function. PMID- 8361103 TI - [Transcranial Doppler monitor in the case of selective cerebral perfusion]. AB - Six patients underwent ascending aorta and aortic arch replacement for aneurysmal disease between 1991.12-1992.2 using the cardiopulmonary bypass technique with selective cerebral perfusion from right axillary artery. For four patients, intraoperative transcranial Doppler monitorings of left MCA flow velocity were done. We added left carotid artery perfusion for 5 patients because of old age; 1, intraoperative finding of anisocoria; 1 and low left MCA flow velocity on the TCD monitor; 3. After the addition of left side perfusion, the left MCA flow velocity on the TCD monitor recovered to normal level in the 3 patients. TCD reflected the cerebral perfusion state every minutes and seemed to be very useful monitor in selective cerebral perfusion. It also suggested that unilateral cerebral perfusion does not supply enough blood flow in contralateral side of brain in many cases. To another patient who also underwent aortic arch replacement, we examined preoperatively left MCA flow velocity on the TCD monitor under left carotid artery compression. This "carotid artery compression test" was thought to suggest the degree of right to left intracranial collateral blood flow via Willis's circle. TCD image, when the left carotid artery was clamped, was compared with the result of preoperative "carotid artery compression test". But we can't evaluate the results quantitatively now. PMID- 8361104 TI - [Surgical treatment of endocardial cushion defect in 3 elderly patients]. AB - We performed surgical treatment for partial endocardial cushion defect in 3 patients over fifty year old. Case 1 was a 55-year-old-male with TR of grade II. Case 2 was a 59-year-old-female with TR and MR, and was repaired mitral cleft by a mattress suture. She needed infusion of dopamine (over 5 micrograms/kg/min) for 6 days and therapy of mediastinitis postoperatively. Case 3 was 56-year-old-male without atrioventricular valve regurgitation. Preoperative left ventricular volume was small in all patients, therefore perioperative circulatory control, mainly water balance, and respiratory control were importance. All patients survived, and both decreasing of CTR and improvement of NYHA classification were recognized in all three patients. In conclusion the operation for ECD in even elder patients was effective, but intensive care needed perioperatively. PMID- 8361105 TI - [Solitary papilloma of the lung: a case report]. AB - A case of solitary papilloma of pulmonary parenchyma is presented. The patient was a 47-year-old woman admitted our clinic because of a mass shadow on routine chest films. The operation was performed without definitive diagnosis of the tumor. Intraoperative frozen specimen revealed to be either papilloma or squamous cell carcinoma. So right upper and middle lobectomies with mediastinal lymph nodes dissection were performed. When a definite diagnosis cannot be proved to be papilloma even at surgery, treatment as a lung cancer should be performed. Solitary benign papilloma like this case is very rare. According to the literature, this case seems to be the first Japanese case of solitary papilloma in pulmonary parenchyma. PMID- 8361106 TI - [A case of hypertrophic obstructive cardiomyopathy using intraoperative trans esophageal echocardiography]. AB - A 45-year-old man underwent trans-aortic myectomy for hypertrophic obstructive cardiomyopathy (HOCM). Although two mounds of hypertrophic septal muscle were resected, Brockenbrough phenomena proved unsatisfactory myectomy. Intraoperative trans-esophageal echocardiogram (TEE) revealed a residual mound at the apical septum. After the additional myectomy, Brockenbrough phenomena was disappeared. Intraoperative TEE is an useful supplement in the operation of transaortic myectomy for HOCM. PMID- 8361107 TI - [A case of primary cardiac hemangiosarcoma]. AB - A case of primary hemangiosarcoma of right atrium was reported. The patient was 43 years old female. She had the symptoms of tamponade due to massive bloody pericardial effusion. Echocardiography, computed tomography, NMR imaging and angiography revealed the precise delineation and extension of tumor, and also allowed diagnosis of hemangiosarcoma. Extirpation of tumor was performed under the cardiopulmonary bypass. The patient was died 3 months later after the operation for liver metastasis. The bloody pericardial effusion seems to be an important symptom of the primary malignant cardiac tumor, and early and precise diagnosis may allow successful operation and long survival of the patients. PMID- 8361108 TI - [Urgent mitral valve replacement for acute mitral regurgitation due to ruptured chordae tendineae in systemic lupus erythematousus]. AB - We reported a successful surgical treatment of mitral regurgitation (MR) due to ruptured chordae tendineae in a 44-year-old man with systemic lupus erythematosus (SLE) who had received the steroid therapy. He had signs of acute congestive heart failure with severe pulmonary hypertension due to MR, and underwent urgent mitral valve replacement. The postoperative course was uneventful. When replacing valve in SLE, a careful manipulation should be taken because of friability of cardiovascular tissue. Patients are usually administered steroid agents, and the agents ought to be discontinued in perioperative period, but it seems to be better to resume as soon as possible. We conclude that the surgical treatment for valvular diseases should be considered, even in the patient with SLE. PMID- 8361109 TI - [A case of coronary artery bypass grafting for single coronary artery complicated by angina pectoris]. AB - A case of coronary artery bypass grafting (CABG) for single coronary artery complicated by angina pectoris (AP) was reported. The patient was a 74-year-old male, complained of anginal discomforts. His single coronary artery originated in left coronary sinus, bifurcated to the left anterior descending artery (LAD) and the circumflex artery (CX), and then, an abnormal communicating branch, passing in front of the right ventricular outflow, was branched from the proximal region of LAD; it showed a route corresponding to the proximal region of the right coronary artery (RCA). The distal region of RCA and the posterior descending artery were angiographed in continuity from CX. Other findings included 75% stenosis at LAD-#6 and 90%-stenosis at CX-#13. Using two saphenous vein grafts, CABG operation was carried out on those regions at LAD-#7 and distal CX corresponding to #3 normally. Postoperatively, anginal discomforts disappeared, and favorable results were obtained. PMID- 8361110 TI - [Successful operation for isolated cardiac rhabdomyoma of the right atrium]. AB - A 12-year-old girl has experienced palpitation and dizziness, and presented atrial flutter with maximal heart rate of 220/min. Two-dimensional echocardiogram and chest MRI revealed a mass attached to the inter-atrial septum. Complete excision of the tumor including the atrial septum was performed without damage to tricuspid valve. The interatrial septal defect was closed primarily. Histology of the tumor was compatible with cardiac rhabdomyoma. Sinus rhythm was present and no tachycardia occurred in the postoperative period. On the literature, only one case of isolated cardiac rhabdomyoma developing in the atrium was reported and this is considered as the oldest operative case in Japan. PMID- 8361112 TI - [A case of chondrosarcoma of the thoracic vertebra]. AB - A case of chondrosarcoma of the thoracic vertebra in a 47-year-old female is described. Chest X-ray, CT and MRI disclosed an abnormal mass lesion in the posterior mediastinum. The lesion was surgically removed through right thoracotomy. The operative findings revealed that the lesion, hard and measuring 6.5 x 4.5 x 4.5 cm in diameter, was originated from the 7th and 8th thoracic vertebra. The lesion was histopathologically diagnosed chondrosarcoma. The chondrosarcoma arising from the thoracic vertebra is very rare, and only 10 cases have hitherto been reported in the Japanese literature. PMID- 8361111 TI - [A case report of graft replacement of the ascending and transverse aorta without homologous red blood cell transfusion]. AB - A 28-year-old man of DeBakey type I dissecting aneurysm was received graft replacement of the ascending and transverse aorta under the deep hypothermic circulatory arrest and continuous retrograde cerebral perfusion for cerebral protection during circulatory arrest. From 3 weeks before operation, autologous blood was collected from the patient with the intravenous administration of a recombinant human erythropoietin (rHuEPO) and was subsequently used in the operation. As result, the graft replacement of the ascending and transverse aorta was performed without homologous red blood cell transfusion and postoperative neurological complications. We believe autologous blood transfusion with rHuEPO and circulatory arrest with CRCP contributes operations of aortic aneurysms without homologous blood transfusion. PMID- 8361113 TI - [A case of intrathoracic colon perforation due to adult Bochdalek hernia]. AB - The patient, a 70-year-old man, diagnosed as having left pneumothorax and hydrothorax, was admitted and had a thoracic drain inserted. The evacuation of stool was noted from 3 days after insertion. With the abscess in the left thoracic cavity shown on emergency CT, a diagnosis of perforation of the digestive tract in the left thoracic cavity was made and emergency operation was performed. On the basis of the intraoperative findings, the case was diagnosed as adult Bochdalek hernia with intrathoracic colon perforation, and repair of hernia and colostomy were done by laparotomy and thoracotomy. However, the patient died of DIC and sepsis 5 days after operation. Two cases of adult Bochdalek hernia complicated with spontaneous pneumothorax have hitherto been report. However, there has been no reported case which had adult Bochdalek hernia complicated with pneumothorax considered due to intrathoracic colon perforation as in this case. So this case was considered very rare and worthy of reporting. PMID- 8361114 TI - [Squamous papillomatosis of the left main bronchus and trachea: a case report]. AB - A 49-year-old female complaining of dyspnea at exercise was admitted. Bronchoscopic examination revealed that the left main bronchus was almost obstructed by a tumor. A sleeve resection of the left main bronchus was performed. Histological examination confirmed that the tumor was squamous papilloma. After one year and eight months, bronchofiber examination disclosed papilloma in the trachea. Therefore, papilloma was treated with endoscopic methods, including Nd-YAG laser. The patient has survived for 11 years since first treatment. PMID- 8361115 TI - [Retreatment of pulmonary tuberculosis--duration of chemotherapy]. AB - Although standard chemotherapy for initial treatment of pulmonary tuberculosis has been established, regimens for retreatment of tuberculosis have not yet been established. One hundred fifty nine retreatment pulmonary tuberculosis cases admitted to Fukujuji Hospital were retrospectively analyzed. Regardless of the age at the start of retreatment, majority of cases were treated previously between 1955 and 1960. Bacillary negative conversion rate, duration of chemotherapy, follow-up period and bacteriological relapse rate were compared according to resistance against isoniazid and/or rifampicin. Sixty four cases were sensitive to both INH and RFP. For this group the average duration of chemotherapy was 14.6 months, mean follow up period was 47.3 months and relapse rate was 3.1%. This rate was similar to that of initial treatment cases. Sixty one (94%), were treated with more than two sensitive drugs containing INH and RFP. The 22 INH-resistant and RFP-susceptible cases were treated for 18.6 months and followed up for 55.2 months. The relapse rate of this group was 13.6%. Thirteen cases were treated with more than 2 sensitive drugs containing RFP. Eleven cases were resistant to both INH and RFP. Five of them were surgically operated of which 3 cases were converted to negative and among the nonsurgical cases in this group only one remained sputum positive. All of these retreatment regimens did not contain pyrazinamide and ofloxacin. Although bacillary positive rate of INH and RFP susceptible cases was 13.0% at 6 months after treatment and 5.3% at 12 months after treatment, that of INH resistant and RFP susceptible cases were 25.0% and 12.5%, respectively. A certain rule of retreatment could be obtained from the result of this study. PMID- 8361116 TI - [Clinical studies on lung disease caused by atypical mycobacteria in our hospital -especially in relation to drug susceptibility]. AB - From 1987 to 1991, 27 patients were diagnosed as atypical mycobacteriosis in our hospital. Some strains of M. avium complex were found to be M. avium and M. intracellulare by means of a DNA probe test. 1. Total cases consisted of 14 males (the average age was 66.7 years) and 13 females (65.7 years). 2. M. avium complex was observed in 24 patients (9 cases of M. avium and 5 cases of M. intracellulare): M. kansasii and M. chelonae were found in 2 patients and 1 patient, respectively. 3. The findings of sputum cultures became negative three months after the chemotherapy treatment in 3 out of 25 patients. Two male patients were operated on and cured. Three patients died, and all of them had respiratory infections. 4. To determine the susceptibility of mycobacteria strains isolated from patients to various antimicrobial agents, an investigation was carried out. There were 88 strains of M. tuberculosis, 52 strains of M. avium complex (23 strains of M. avium and 17 strains of M. intracellulare), 3 strains of M. kansasii, 2 strains of M. gordonae and 2 strains of M. chelonae. 5. Strains of M. tuberculosis, M. kansasii and M. gordonae were susceptible to various antituberculous agents and ciprofloxacin. Strains of M. chelonae were susceptible to ciprofloxacin, and one strain was susceptible to streptomycin and ethionamide. 6. The M. avium strains were more susceptible to cycloserine and ciprofloxacin than were the M. intracellulare strains. Conversely, the M. intracellulare strains were more susceptible to ethambutol than were the M. avium strains. PMID- 8361117 TI - [A survey of the initial course of tuberculosis chemotherapy under compulsory hospitalization on the basis of the revised Tuberculosis Prevention Law--report of the 32nd C series of controlled trials of chemotherapy--Cooperative Study Unit of Chemotherapy of Tuberculosis of the National Sanatoria in Japan]. AB - We studied 2247 patients with pulmonary tuberculosis who were hospitalized for the initial course of chemotherapy under the provision of the revised Tuberculosis Prevention Law issued by Japanese Ministry of Welfare. The results were as follows. 1) There were more males than females with a ratio of 2.6: 1. 2) There were two peaks in their ages, 20s and 60s. 3) The average admission periods were 5.2 +/- 2.7 months for men and 5.1 +/- 2.8 months for women. 4) The average compulsory admission periods were 6.8 +/- 2.5 months for men and 6.4 +/- 2.3 months for women, so that the actual admission periods were shorter in the majority of the patients. 5) The sputum cultures were converted negative in three months in about 80 percent of the patients who were smear and/or culture positive on admission. 6) The appearance rate of INH-resistant and RFP-resistant strains were 2% and 1.4% respectively. 7) Most of the death from tuberculosis was observed in the early stages of admission. 8) With regards to the cost, there seemed to be no difference whether treated under the new or the old provisions. 9) The newly approved extension of the admission periods for those who had complications such as diabetes mellitus or pneumoconiosis and those who had INH and/or RFP positive bacilli seemed to be appropriate. PMID- 8361118 TI - [A case of oral tuberculosis suspected malignancy]. AB - Oral tuberculosis with pulmonary tuberculosis is very rare in Japan. A 45-year old man admitted to our hospital because of spontaneous teeth extraction and pain in oral cavity for the past 3 months. The painful granulation in palate and fistel of 7th tooth root defect in right upper gum were observed. The diagnosis of oral tuberculosis was made by the histological examination of biopsy material and positive smear test for M. tuberculosis in surface of granulation. Chest X ray showed multicavitary lesions in bilateral upper lobs and spread shadows in bilateral lower lung fields. He was treated with chemotherapy (INH, RFP, SM and EB) and with tube feeding. Five month's chemotherapy was needed to achieve cured granulation and negative smear test for M. tuberculosis in sputum. He was discharged 10 months after admission. PMID- 8361119 TI - Proceedings of the Priscilla Kincaid-Smith Festschrift. Melbourne, Australia, November 5-8, 1991. PMID- 8361120 TI - A specific glomerular lesion of the graft: allograft glomerulopathy. AB - During the period from January 1973 to December 1970, 774 renal transplantations in 698 children have been performed in our Renal Unit. A total of 540 grafts have been examined both by light and immunofluorescence microscopy at least once. Recurrent glomerulonephritis was diagnosed in 62 grafts, de novo glomerulonephritis in 68 and allograft glomerulopathy (AGP) in 38. AGP was defined as a lesion affecting all glomeruli and characterized by widespread reduplication of the GBM with widening of the subendothelial space and interposition of mesangial matrix and without significant deposits by immunofluorescence. The aim of the current study is to describe the natural history of AGP and to delinate its clinical significance. At time of biopsy, an increase in serum creatinine was present in 30 patients associated with a proteinuria > or = 1 g/day in 21. During the post-transplantation course, proteinuria was present in 29 patients and associated with a nephrotic syndrome in 10 of them. With a mean follow-up of eight years seven months, two patients died, 23 lost their grafts and 13 have a functioning graft. The lesions of AGP recurred in three of the nine children who received a second graft. Thirteen of the 33 patients in whom earlier biopsies were performed showed a different pattern of involvement characterized by a prominent swelling of active endothelial and mesangial cells and a hypercellularity related to the presence of mononuclear cells both in the lumens and in the mesangial areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361121 TI - Future directions in transplantation: xenotransplantation. AB - Xenotransplantation would overcome the worldwide shortage of organs for transplantation. However, xenotransplantation using primate organs is unpracticable, and xenotransplantation between phylogenetically disparate species results in hyperacute rejection. This fulminant form of rejection is mediated by both naturally occurring xeno-antibodies and by direct activation of the alternative pathway of complement. The precise specificities of the xeno antibodies are incompletely understood and better characterization of these antibodies and their target antigens is needed to allow the development of therapeutic maneuvers, such as immunoadsorption of the relevant antibodies. The direct activation of the alternative pathway of complement by xenogeneic tissue is due, at least in part, to the lack of appropriate (human) membrane bound regulators of complement on the xenogeneic cells. These regulatory molecules, called homologous restriction factors, are species specific, and act to favor inactivation of the complement cascade if the complement is of the same species. Human homologous restriction factors are capable of protecting xenogeneic cells from lysis mediated by human complement. The study of cell-mediated rejection in xenotransplantation has been largely overshadowed by hyperacute rejection. Resolution of the barriers to xenotransplantation will benefit the ever growing number of patients awaiting transplantation. PMID- 8361122 TI - Deficiency and depletion of complement in the pathogenesis of nephritis and vasculitis. PMID- 8361123 TI - Pathogenesis of glomerulonephritis. AB - This review summarizes current understanding of the mechanisms which mediate immune glomerular injury in glomerulonephritis. Non-inflammatory lesions resembling minimal change disease and membranous nephropathy, respectively, are induced by non-complement fixing antibodies to glomerular epithelial cell (GEC) membrane antigens (minimal change disease) and GEC membrane insertion of the C5b 9 membrane attack complex of complement (membranous nephropathy). The cellular mechanisms of these effects are unclear but may involve GEC activation and release of local mediators, such as proteases or oxidants, or GEC detachment from underlying basement membrane. Inflammatory types of glomerular lesions are mediated by circulating inflammatory cells (neutrophils, platelets, macrophages) or by resident glomerular cells (mesangial cells) or both. Neutrophil-mediated injury involves local release of GBM degrading proteases or GBM halogenation induced by the interaction of neutrophil-derived myeloperoxidase with H2O2 and a halide. Neutrophil induced glomerular injury is augmented by platelets. Recent evidence establishes that mesangial cell proliferation in glomerulonephritis is mediated by complement and platelets. Mesangial cell proliferation is accompanied by increased expression of PDGF and PDGF receptor proteins and the genes for these proteins resulting in an autocrine mechanism of cell proliferation. Mesangial cell proliferation is also accompanied by increased release of neutral proteinase in sites of basement membrane damage. Mesangial cell proliferation precedes up-regulation of genes for extracellular matrix components in several models and may be important in the pathogenesis of glomerulosclerosis. PMID- 8361124 TI - The contributions of Priscilla Kincaid-Smith to the study of glomerulonephritis: a personal view. PMID- 8361125 TI - Role of leukocyte-endothelial cell adhesion molecules in renal inflammation: in vitro and in vivo studies. AB - An increasing body of evidence suggests that endothelial cells as well as parenchymal cells within the kidney express multiple cytokine-inducible leukocyte adhesion molecules. This paper reviews evidence from our own laboratory as well as others on the in vitro induction and function of adhesion molecules in the kidney. We review current data from the literature on the possible role of endothelial cell adhesion molecules in mediating leukocyte infiltration and renal injury in experimental and human transplant rejection and glomerulonephritis. These early studies suggest that leukocyte-endothelial adhesive interactions result in a complex cascade of biological and pathological processes leading to renal injury. Further analysis of such interactions in the kidney will elucidate their specific roles. PMID- 8361126 TI - The glomerular peripolar cell. AB - The PPC is a distinctive granulated epithelial cell at the vascular pole of the glomerulus. It is present in a wide range of animal species. It is especially prominent in sheep, particularly the newborn lamb. To date, it has been shown that its granules contain albumin, immunoglobulins, neuron-specific enolase and transthyretin. It does not appear to contain renin. The function of the PPC awaits clarification. It has been postulated that it may play a role in the synthesis and secretion of factors involved in modulating renal tubular function. PMID- 8361127 TI - Localization and properties of angiotensin II receptors in rat kidney. PMID- 8361128 TI - Renal gene expression. AB - The advent of cloned DNA probes has revolutionized the study of cells and tissues via the technique of hybridization histochemistry. Because of the intrinsic specificity of the probes the application of the technique to functionally complex and morphologically diverse tissue like the kidney has been especially rewarding. The technology has been advanced enormously by the parallel development of synthesized DNA or oligonucleotides. A specific synthetic probe can be manufactured in a day, purified, labeled and used to determine in which cells a particular gene of interest is being expressed ("switched on"). The applications of this technology are particularly opposite in the renal field. They can provide unique insights into normal physiological processes and will provide new diagnostic approaches of unparalleled specificity. Some specific examples have been chosen over a wide range of institute programs to highlight the potential value of the technique of hybridization histochemistry and to emphasize its potential for studying renal physiology and pathology. PMID- 8361129 TI - Contributions of Priscilla Kincaid-Smith to hypertension. PMID- 8361130 TI - Hypertension and the kidney. AB - From our perspective, Priscilla Kincaid-Smith's major achievement in the field of hypertension relates to the pathogenesis of vascular lesions. Our own studies of the hypertension of renal parenchymal disease have suggested a role for impairment of the cortisol-cortisone shuttle and decreased activity of the enzyme complex 11-beta-hydroxy-steroid dehydrogenase. We have defined the renal functional consequences of steroid-induced hypertension and shown that the rise in blood pressure produced by steroids with predominant glucocorticoid activity is not dependent on volume shifts or sodium status, although the magnitude of the rise is modulated by dietary sodium content. We have shown that normal pregnant women adapt readily to extremes of sodium intake while women with pre-eclampsia retain sodium, and have shown enhanced capillary permeability. Recent studies have defined an abnormal aldosterone:renin ratio, dopaminergic inhibition of aldosterone, elevations of plasma atrial natriuretic peptide and reduced urinary prostacyclin:thromboxane ratios in women with pre-eclampsia. PMID- 8361131 TI - Intrarenal renin-angiotensin system in renal physiology and pathophysiology. AB - It has now been demonstrated by several techniques that all components of the renin-angiotensin system reside within the kidney. It is likely that angiotensin II is formed within interstitial renal tissue, as well as intracellularly, and acts locally in an autocrine, paracrine or intracrine manner. It has been difficult to dissect the different renal physiological roles of circulating angiotensin II as opposed to intrarenal generated angiotensin II. Angiotensin converting enzyme (ACE) inhibitors have played an important role in helping distinguish the effects of intrarenal angiotensin. Apart from hemodynamic actions and effects on glomerular filtration rate and renal tubular function, the intrarenal renin angiotensin system probably plays an important role as a regulator of renal sympathetic activity, modifies mesangial cell function, acts as a renal growth promoter, maintains endothelial cell function, and may be an important inflammatory mediator in the kidney. The renoprotective action of ACE inhibitors in reducing proteinuria and in slowing the fall in glomerular filtration rate in experimental and human renal disease may involve any of the above mechanisms. However, a prerequisite for the renoprotective action of ACE inhibitors is reduction of systemic blood pressure. PMID- 8361132 TI - Aspects of renal disease and pregnancy. PMID- 8361133 TI - Drug treatment of hypertension. AB - Over the last 40 years effective drug treatment of hypertension has become available. Newer classes of drugs offer efficacy with simplicity of dosing regimen and good patient acceptability. However, there is increasing interest in the long-term benefits of treatment, particularly influences on total mortality and morbidity and mortality from coronary artery disease and its complications. Established treatments with diuretics and beta blockers do reduce stroke risk but have less than predicted effects on coronary heart disease. While there is experimental evidence and clinical pointers that ACE inhibitors and calcium antagonists may influence atherosclerosis in the long-term, there is as yet no objective clinical confirmation. The aim of treatment in the 1990s is to control blood pressure (and other risk factors) in the short-term with a view to improving long-term outcome. Many clinicians have modified step-care approaches to individualize drug treatment using one or two agents, selected from older and newer classes, which on clinical grounds are most appropriate in the individual patient. Factors determining choice are race, other risk factors and associated diseases. PMID- 8361134 TI - Chronic tubulo-interstitial nephritis: the contributions of Priscilla Kincaid Smith. PMID- 8361135 TI - Clinical management of autosomal dominant polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is a common systemic genetic disease which comprises 8 to 10% of patients treated by dialysis and transplantation. Breakthroughs in molecular genetics and cell biology have led to new insights into cyst formation and growth. Until the specific genetic defects are identified, the management of this disorder will necessarily be empiric. This paper discusses current management strategies in ADPKD focusing on hypertension, hematuria, pain and infection. Special considerations for management of end-stage renal failure in patients with ADPKD are also reviewed. PMID- 8361137 TI - Analgesic nephropathy in the 1990s--an Australian perspective. AB - Analgesic nephropathy or analgesic abuse-associated analgesic nephropathy (AA AAN) is a disease of the twentieth century. The emergence of AA-AAN was due to aggressive marketing of analgesics and the susceptibility of individuals with addictive personalities to analgesic abuse. Analgesic abuse resulted in major morbidity and mortality from renal disease and renal failure, premature atherogenesis with cardiovascular diseases, and the other aspects of the analgesic syndrome; these conditions have had heavy demands upon health budgets. Legislative restriction of analgesic sales in Australia has resulted in a decline in analgesic abuse and end-stage renal failure from AA-AAN. There have also been changes in the analgesic syndrome. However, the long-term risks of transitional cell carcinoma of the uroepithelium remain as a legacy of analgesic abuse and AA AAN. Nonsteroidal anti-inflammatory drug-associated analgesic nephropathy (NSAID AAN) has emerged as a distinct clinical syndrome, and may become a significant health problem in view of the widespread use and misuse of NSAIDs. PMID- 8361136 TI - Vesico-ureteric reflux and reflux nephropathy. PMID- 8361138 TI - Microscopic urinalysis in glomerulonephritis. PMID- 8361139 TI - Lithium nephrotoxicity. AB - After nearly two decades of concern and controversy surrounding the long-term effects of lithium on the kidney, the fact that lithium is capable of causing a major disturbance in water balance, manifest as polyuria and secondary polydipsia, remains undisputed. A decreased urinary concentrating ability (nephrogenic diabetes insipidus) with a disturbed responsiveness of the distal nephron to the action of ADH (vasopressin) is demonstrable, and the symptoms are largely reversible on cessation of lithium or reduction of the dose. An acute histological lesion of the distal nephron, corresponding to the site of lithium inhibition of the action of ADH, and consisting of epithelial cellular swelling and glycogen deposition, also appears to be readily reversible. Of greater concern is the development of a progressive impairment of urinary concentrating ability in patients on long-term maintenance therapy--especially those with a history of acute lithium toxicity and those additionally treated with neuroleptics. This functional lesion is not always reversible, and the underlying renal histology is a chronic focal interstitial nephropathy. Interestingly, some psychiatric patients never exposed to lithium have demonstrated similar renal histology. There is very little evidence that stable maintenance lithium therapy, without episodes of acute intoxication, is associated with a reduction of glomerular filtration rate. Episodes of acute lithium intoxication are largely predictable, and therefore avoidable, provided appropriate precautions are taken. Patients with polyuria and impaired urinary concentrating ability are at increased risk of acute lithium toxicity because of excessive renal losses of fluid, and these symptoms should be treated in the first instance with dosage reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361140 TI - Renal transplantation: contributions of Priscilla Kincaid-Smith. PMID- 8361141 TI - [Sinobronchial syndrome--a meaningful diagnosis?]. AB - The term sinobronchial syndrome is often used, but there is no generally accepted definition. Due to the functional and clinical unity of the whole respiratory tract infectious and allergic irritations lead to homogeneous reactions of the bronchi and the paranasal sinuses. On the other hand there are hints that a disease in one region can cause problems in the other or reinforce it. Probably bronchi and sinuses can also become infected simultaneously from the pharynx. In chronic cases sinusitis and bronchitis are often only symptoms masking an underlying disease that requires differentiated diagnostics and treatment, e.g. cystic fibrosis, primary ciliary dyskinesia, and immunological defects. PMID- 8361142 TI - [Follow-up and prognosis of pyelonephritis in infancy]. AB - 128 infants between 1 and 18 months, 80 girls and 48 boys suffering from their first pyelonephritis (PN), were investigated and followed up over 2.9 +/- 2.2 years (mean +/- SD). 20 children showed urinary tract obstructions. In 49 of 108 cases (45%) with nonobstructive PN a vesico-uretero-renal reflux (VUR) was found and surgically corrected in 13 cases. In 36 patients (52 renal units) the VUR disappeared in most cases under medical management within 3 years. Recurrences of urinary tract infections (UTI) were found in the same frequency in children with and without reflux (28%), but those with VUR showed significantly more PN. 22 of 108 patients with nonobstructive PN (20%) developed renal scars, 39% of children with reflux (mostly VUR III. or IV. degree), 5% of those without reflux. In more than half of these cases renal scars were found already after the first PN. We conclude that a reduction of the risk of renal damage and an improvement of the prognosis can achieved by the following measures: 1. early detection of obstruction by pre- or postnatal sonographic screening, 2. early and exact diagnosis of PN and antibiotic therapy without delay. PN has to be excluded in all infants with unclear fever. 3. In all infants with PN a voiding cystography should be performed. In children with VUR, long-term chemoprophylaxis is necessary to avoid recurrence of PN. PMID- 8361143 TI - [Hirschsprung disease. Discussion of a disease picture also relevant to neonatology]. AB - The clinical disease pattern of an "acute abdomen" is by no means rare in newborn and very young infants and always signals an emergency situation. Besides inflammatory causes, congenital anomalies are among the most prominent reasons responsible for this condition. The example of 3 own patients serves to illustrate the disease pattern of Hirschsprung's disease, which is discussed with special reference to neonatology. PMID- 8361144 TI - [Correlation between glycemia control and lipid metabolism parameters in children with diabetes mellitus]. AB - Screening for hypercholesterolaemia and hypertriglyceridaemia should be considered in children with diabetes mellitus. Studies on different serum lipids in children with Type I diabetes have shown different results. Hyperglycaemia is the primary abnormality of diabetes. It is logical to consider elevated blood glucose as a possible risk factor in the development of macrovascular disease. Although associations between hyperglycaemia and diabetic complications have been repeatedly shown for microvascular disease, such an association is weaker for macrovascular disease. We report on the results of estimations of different serum lipids in 78 children with diabetes mellitus. These results are compared with those of assessment of the quality of glycaemic control. The results show an association between the quality of glycaemic control and the height of triglycerid concentrations. There were no associations between the quality of glycaemic control and LDL- and HDL-cholesterol. Cholesterol showed only a weak association to glycaemic control. In nearly all patients HDL-cholesterol was estimated to be in the upper normal range. The results are discussed in respect of possible risks for the development of macrovascular disease. PMID- 8361145 TI - [Treatment of ocular toxoplasmosis. Part 2: Therapeutic approaches]. AB - Retinochorioditis is the most common complication of ocular toxoplasmosis and also the most dangerous one in respect of central visual acuity. New treatment concepts are increasingly replacing the therapy that had become established since the fifties and that had been based on pyrimethamine and sulphadiazine. The new concepts entail fewer complications and are better accepted by the patients. However, prospective randomised studies that are based on severe criteria could not prove for any of the employed treatment courses that it promotes healing of retinochorioditis or prevents relapses. However, if central visual acuity is endangered, drug therapy should nevertheless be initiated. In babies and in persons with immunodeficiency treatment must be in accordance with the overall pattern of symptoms. PMID- 8361146 TI - [A further case with Baller-Gerold syndrome (craniosynostosis--radial aplasia syndrome)--overview and new viewpoints on a rare syndrome]. AB - The Baller-Gerold syndrome is a rare malformation syndrome with craniosynostosis. A radial defect is the main feature of this combination besides the premature craniosynostosis. The entity and the etiology of this inherited trait was often discussed in recent years. This syndrome is further characterised and presented as a distinct entity with the reported new case. Parents of such a child should be aware of the 25% recurrence risk in subsequent siblings because of an autosomal recessive mode of inheritance. PMID- 8361147 TI - [Preventive vaccinations 10 years after treatment of undifferentiated malignant blastoma?]. PMID- 8361148 TI - [Increased risk of invasive bacterial infections after preventive mumps-measles rubella vaccination?]. PMID- 8361149 TI - [The physician as expert witness. Aspects of an ambivalent role exemplified by expert testimony for legal health insurance]. AB - This article provides a broad survey of the difficulties confronting the physician in his role as a specialist in the Health Insurance Medical Service, assessing claims relating to the state medical insurance system. These problems can be divided into the three following categories. Firstly, problems on a personal level relating to the interaction of the different people involved, albeit within the given institutional framework. Secondly, problems involving matters of principle in reconciling diagnosis, the patient's subjective assessment of his condition and legal criteria. Thirdly, problems arising from the pressure created by socio-cultural developments which influence both the patient and the specialist physician in his assessment. PMID- 8361150 TI - Volume profiles obtained by a conductimetric method. AB - One problem faced by intracardiac conductance volumetry is the non-uniform distribution of the injected current. Salo, in 1989, proposed a method to correct this undesirable effect. The objective here is to test Salo's method in known volumes of simple geometry by obtaining volume profiles. A plastic rod with 15 metallic rings simulated the conductance catheter. Five sections were used for the resistance measurements employing the upper electrode as fixed current source and the lowest one as the shifting source. This is part of Salo's procedure. The source-to-section distance was measured from the moving source to the section (linear definition) or using the equivalent distance concept (Salo's). Thereafter, each sectional resistance set of values was plotted as a function of the inverse of the source-to-section distance (either definition) elevated to an empirical exponent k to obtain the corrected sectional resistance by extrapolation back to zero of the regression line, i.e., a value produced by a source theoretically placed at infinity. In addition, a mathematical analysis was attempted, searching for an optimum k based on minimum volume error. The best volume profiles for two cylinders and a frustum were obtained with k = 2 using the linear definition of distance (errors of -3.49%, -1.25% and -3.65%, respectively). Moreover, the frustum angle was determined within 0.4 degrees (2.7%) of the real value. The theoretical analysis led to an inverse logarithmic relationship between the exponent k and the source-to-section distance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361151 TI - Microcomputer-based system for automatic analysis of M-mode echocardiograms. AB - A microcomputer-based system has been developed for automatically analysing M mode echocardiograms. This system can be used on images directly transferred from an echograph to the microcomputer. To obviate the major disadvantage of echocardiography, its poor signal-to-noise (S/N) level, the system conducts, first, an image restoration based on the quasi-periodicity of cardiac cycles, then border extraction is performed, using methods based on template matching using dynamic cardiac information present in the echocardiograms. PMID- 8361152 TI - Changes in oscillometric pulse amplitude envelope with cuff size: implications for blood pressure measurement criteria and cuff size selection. AB - Oscillometric blood pressures are derived from the amplitude envelope of oscillometric pulses generated in an occlusive cuff during cuff inflation or deflation; one factor which will affect the characteristics of these pulses is the size of the cuff bladder. Because limiting values are stipulated in recommendations and standards for bladder sizes, there is a wide variety of acceptable cuff sizes for any particular application. An experimental and theoretical study was undertaken to show the dependence of oscillometric blood pressures on bladder size. Actual cuff-arm compliance data were obtained from two subjects for two cuffs of different bladder size. Theoretical analysis was then applied to the data to predict the effects of different bladder sizes on the characteristics of the pulses. The results show that cuff-arm compliance and bladder size interact to affect the pulse amplitude and hence oscillometric blood pressure determination. These results suggest that blood pressures obtained using the oscillometric method may vary depending on cuff size, and in particular that replacement cuffs for oscillometric non-invasive blood pressure monitors should be chosen carefully. PMID- 8361153 TI - Dynamic model of the bronchial tree. AB - We present a distributed model of the bronchial tree which simulates the global dynamic characteristics of the lung. Local mechanical characteristics of each airway are represented by RCL circuits and parameters of the electrical components are determined from local physiological data. The bronchi geometry is described by Weibel's symmetric model, the flow in each airway is assumed laminar and mixing effects at the bifurcations are neglected; the transpulmonary pressure is assumed to be sinusoidal. In simulations of quiet breathing the resistance to airflow is found to be dominant, the flow amplitude decreasing as breathing frequency increases, but remaining almost constant in all the generations. Simulations of ventilation through obstructed lungs show frequency dependence of the dynamic characteristics in very compliant lungs. The global resistance to airflow and the dynamic compliance of the bronchi decrease as the forced oscillation frequency increases in a pattern similar to in vivo measurements in diseased lungs. This may be an outcome of the RCL properties of the network rather than due to uneven distribution of mechanical properties of the lung. PMID- 8361155 TI - Novel monochromatic optical density meter. AB - A novel monochromatic optical density meter is described for use with radiographic films. The principles of the instrument are outlined together with a brief description of the construction of a prototype model. The calibration of the meter shows high accuracy (r = 0.9999) in the optical density range 0-1.5 OD when compared to standard neutral density filters. PMID- 8361154 TI - A three-dimensional anatomical model of the human patello-femoral joint, for the determination of patello-femoral motions and contact characteristics. AB - The object of this study is to develop a three-dimensional mathematical model of the patello-femoral joint, which is modelled as two rigid bodies representing a moving patella and a fixed femur. Two-point contact was assumed between the femur and patella at the medial and lateral sides and in the analysis, the femoral and patellar articular surfaces were mathematically represented using Coons' bicubic surface patches. Model equations include six equilibrium equations and eleven constraints: six contact conditions, four geometric compatibility conditions, and the condition of a rigid patellar ligament; the model required the solution of a system of 17 nonlinear equations in 17 unknowns, its response describing the six degrees-of-freedom patellar motions and the forces acting on the patella. Patellar motions are described by six motion parameters representing the translations and rotations of the patella with respect to the femur. The forces acting on the patella include the medial and lateral component of patello-femoral contact and the patellar ligament force, all of which were represented as ratios to the quadriceps tendon force. The model response also includes the locations of the medial and lateral contact points on the femur and the patella. A graphical display of its response was produced in order to visualize better the motion of the components of the extensor mechanism. Model calculations show good agreement with experimental results available from the literature. The patella was found to move distally and posteriorly on the femoral condyles as the knee was flexed from full extension. Results indicate that the relative orientation of the patellar ligament with respect to the patella remains unchanged during this motion. The model also predicts a patellar flexion which always lagged knee flexion. Our calculations show that as the angle of knee flexion increased, the lateral contact point moved distally on the femur without moving significantly either medially or laterally. The medial contact point also moved distally on the femur but moved medially from full extension to about 40 degrees of knee flexion, then laterally as the knee flexion angle increased. The lateral contact point on the patella did not change significantly in the medial and lateral direction as the knee was flexed; however, this point moved proximally toward the basis of the patella with knee flexion. The medial contact point also moved proximally on the patella with knee flexion, and in a similar manner the medial contact point on the patella moved distally with flexion from full extension to about 40 degrees of flexion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8361156 TI - Stress analysis of endosseous implants using the Boundary Integral Equation (BIE) method. AB - The Boundary Integral Equation (BIE) method for modelling mathematically an endosseous implant within its bony surroundings is described in this study. The results are compared to those calculated by Finite Element Analysis (FEA), and the following conclusions drawn: both FEA and BIE are able to provide stress analyses of the dental implant situation and give similar numerical values of stresses and strains at the implant-bone interfaces. The BIE method does not produce a pictorial representation of the calculated stresses in the form of stress contours, as this is not applicable to boundary investigations. It is easier to alter the outline of the implant with line elements than with solid elements; therefore slight alterations in the outline form of an implant are easy to investigate with regard to their resultant interfacial stress levels. The BIE method is simpler to use than FEA, but little software is commercially available. The aim of the study was to determine whether future developments in this field could be useful in the stress analysis of endosseous implants. PMID- 8361157 TI - Stresses at the meniscofemoral joint: elastostatic investigations on the applicability of interface elements. AB - Stress distributions at the meniscofemoral joint were analysed and the applicability of nonlinear interface elements in a finite element model (FEM) were tested. Centred and 70% off-centre load cases with a complete, a partially removed or a totally removed medial meniscus were evaluated in two dimensions. Interface width was assumed to increase linearly from almost zero to 1 mm at the inner and outer border of the femoral condyles. Maximum interface forces were found at the centre of the condyles, decreasing to zero at the peripherical and intercondylar femoral border. Simulation data concerning a removed medial meniscus or medial 70% off-centre load with complete meniscus indicated higher medial contact forces in the first case. A decrease in the elastic modulus of the articular surface tissues caused two small force transfer peaks (femoral centre and intercondylar border), which were strongly influenced by the predefined gap width. PMID- 8361158 TI - Repeatability of subject/bed interface pressure measurements. AB - The repeatability of a technique for measuring interface pressures has been assessed. Pressure was measured using a Talley SA500 Pressure Evaluator under six anatomical sites (occiput, scapula, elbow, sacrum, buttock, and heel) of six healthy subjects lying supine on a Clinifloat mattress (trademark, SSI). For each site of each subject, four repeat readings were taken per day on four separate days. Mean pressures varied significantly between subjects (p < 0.02), though differences in mean pressures between sites were greater. Pressure was not significantly related to subject mass. The overall repeatability of the technique was +/- 0.77 kPa (+/- 5.8 mm Hg) which was much smaller than the range of pressures found under different sites (2.72 kPa or 20.4 mm Hg at the sacrum to 9.00 kPa or 67.5 mm Hg at the heel). Repeatability varied from site to site, from +/- 0.47 kPa (+/- 3.5 mm Hg) at the buttocks to +/- 1.20 kPa (+/- 9.0 mm Hg) at the heel. Measurements were found to vary significantly more between days than between repeats on the same day (p < 0.02). PMID- 8361159 TI - Computer-controlled portable stimulator for paraplegic patients. AB - A six-channel lightweight, portable and computer-controlled stimulator for the functional activation of paraplegic patients is described. To enable programming of the various functions, the stimulator was designed to work in a remote-control mode hosted by an IBM PC or compatible computer, in addition to its normally used local mode. The stimulus parameters, including current intensity, stimulus frequency and pulse width, are individually adjustable and programmable for each channel. The power source is 12 V 500 m Ah-1, from 10 rechargeable nickel cadmium batteries, with a run time of 1.5 h for a load of 200 mA in four channels. Various training programmes for the activation of paraplegics in the sitting, standing and walking positions are described. The final design of the stimulator is based on experience gained from 25 patients, treated and evaluated during the course of development. Ongoing work including clinical, biomechanical and physiological studies is carried out to evaluate performance of the activated patients and to optimize stimulation. PMID- 8361160 TI - Quantification of soft-tissue imbalance in condylar knee arthroplasty. AB - Soft-tissue balance has been debated in recent publications in connection with the long-term survival of the 'condylar-type' knee prostheses. Present methods of assessment have all assumed that the soft tissues around the knee are inelastic strings. The authors have developed two instruments to quantify soft-tissue imbalance, at the time of the operation, with the assumption that the soft tissues are viscoelastic structures. These two soft-tissue balancing devices were consequently used on 121 patients undergoing condylar knee arthroplasties at the Derbyshire Royal Infirmary and Bretby Hall Orthopaedic Hospital. The first instrument consisted of two flat plates separated by four standard compression springs and provided a qualitative measure of imbalance assuming that the soft tissues were viscoelastic. It was used on 55 patients before being replaced by the quantitative measure of the second instrument. The authors have redefined soft-tissue imbalance, to take into account the viscoelastic nature of the soft tissues, as the resultant trapezoidal geometry of the knee after the bony cuts have been made and when the knee is tensed by equal forces both medially and laterally. The second balancer eliminates the requirement to quantify the individual tensions in the medial and lateral structures by introducing to the system a low-friction, central pivot in the coronal plane. Once the pivot is situated at the centre of the knee, an equilibrium position is achieved where the clockwise and counter-clockwise moments are equal. The tensions exerted by soft tissues can be assumed to be equal and opposite as their moment arms are the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361161 TI - Accuracy of interface pressure measurement systems. AB - Interface pressure measurement is needed to assess beds designed to prevent pressure sores, so it is therefore important to establish the accuracy of interface pressure measuring systems. In this study, the Talley SA500 pressure evaluator (with 28 mm and 100 mm sensor pads), the DIPE (with 100 mm sensor pad), and a water-filled bladder system (with 0.1 ml and 0.3 ml water) were assessed. Measurement errors were evaluated using a loading system with pressures up to 7.4 kPa (55 mm Hg) in steps of 0.9 kPa (6.9 mm Hg). All systems tested over-measured interface pressure, the error being approximately linearly proportional to the loading pressure. The repeatability for a given system was approximately constant. The mean error (+/- SD) (%) and repeatability (kPa) for the systems were: 28 mm Talley 12 +/- 1%, +/- 0.07 kPa; 100 mm Talley 15 +/- 1%, +/- 0.07 kPa; DIPE 27 +/- 3%, +/- 0.12 kPa; 0.1 ml water bladder 17 +/- 1%, +/- 0.13 kPa; 0.3 ml water bladder 26 +/- 3%, +/- 0.07 kPa. Different interfaces affected accuracy markedly, and repeatability was affected when an inhomogeneous interface was used. The study shows that the errors associated with interface pressure measurement systems can be substantial, and can vary from one system to another. PMID- 8361162 TI - Sustained slow sinus rhythm entrained by retrograde atrial impulses. AB - Sustained slow sinus rhythm due to a returning cycle after a premature atrial P wave is described. It seems possible to consider a model of the forced vibration in a spring-mass system or resonant electric circuit of an alternating current series element containing resistance R, inductance L, and capacitance C as a quantitative approach to describing the slow sinus rhythm. The differential equation expressing cardiac resonant oscillation has for the case R = 500 omega the form 178 (d2X/dt2) + 500(dX/dt) + 5600X = 4490 cos 3.57t, where X is 100q, where q is the capacitor charge. By solving the equation of this special case, we obtained an effective voltage and current of 0.84 V and 1.68 mA, respectively. Determination of cardiac electrical activity by this method was considered to be useful, and may have practical applications in solving problems of nearly linear resonance in vital phenomena. This is the first paper on applying a linear second order differential equation to describing a frequency response modelling of slow sinus rhythm due to entrainment by the retrograde atrial impulses. PMID- 8361163 TI - Bombesin-stimulated acetylcholine release from myenteric plexus neurons. AB - The ability of bombesin to stimulate acetylcholine release from guinea pig myenteric plexus neurons was studied using a primary neuronal culture system. Bombesin caused dose-dependent increases in [3H]-acetylcholine (ACh) release from guinea pig myenteric plexus neurons. ACh release in response to 0.5 mM bombesin (160 +/- 12% of control) was blocked by exposure to a calcium-free medium (116 +/ 13%) by nifedipine (101 +/- 11%) and by omega conotoxin (107 +/- 10%). Bombesin stimulated ACh release was inhibited the protein kinase C inhibitor, H7, but was not affected by inhibitors of the cAMP signaling pathway. Interactions with inhibitory neuropeptides was implied by sensitivity of bombesin-stimulated ACh release to neuropeptide Y and galanin. The findings suggest that bombesin activation of protein kinase C in myenteric neurons results in increased acetylcholine release. PMID- 8361164 TI - Endotoxin increases hepatic glutamine transport activity. AB - Glutamine uptake by the liver is accelerated during endotoxemia, but little is known regarding the influence of sepsis on the plasma membrane transport systems catalyzing hepatic glutamine uptake. We hypothesized that this augmented uptake was due to an increase in hepatocyte plasma membrane transport activity. We investigated the activities of the Na(+)-dependent transport System N (transports glutamine into the hepatocyte) and the Na(+)-independent System n (transports glutamine out of the cell) in hepatocyte plasma membrane vesicles (HPMVs) prepared from livers of rats treated with Escherichia coli endotoxin (LPS) in vivo. HPMVs were prepared by differential centrifugation and the transport of [3H]glutamine was assayed by a rapid mixing/filtration technique in the presence and absence of sodium. Vesicle integrity and functionality were confirmed by enzyme marker enrichments and classic "overshoots" in the presence of sodium. Carrier-mediated Na(+)-independent glutamine transport activity was not altered by LPS administration. In contrast, endotoxemia resulted in a time- and dose dependent two- to threefold increase in Na(+)-dependent glutamine transport activity in HPMVs secondary to an increase in the transport Vmax, consistent with the appearance of increased numbers of corresponding transporter proteins in the hepatocyte plasma membrane. The Km (affinity for glutamine) of the System N transporter was not affected by LPS treatment. Maximal increases in transport were observed 4 hr after exposure to endotoxin. System N transport activity returned to basal levels by 12 hr. This increase in transport activity represents an important mechanism regulating the accelerated hepatic glutamine uptake that occurs during severe infection. PMID- 8361165 TI - Lanthanide "blockade" of antigen-presenting cells suppresses lymphocyte proliferation by inducing nitric oxide synthesis. AB - Introduction of antigen into the portal venous circulation can induce a state of antigen-specific tolerance. Reversal of this phenomenon by the administration of gadolinium chloride (GD) before portal venous inoculation with antigen has been thought to result from the inhibition of macrophage phagocytosis by GD, thereby permitting passage of antigen through the hepatic sinusoids into the systemic circulation where sensitization can occur. We recently demonstrated that i.v. GD also greatly enhances the ability of the hepatic macrophage, or Kupffer cell (KC), to suppress lymphocyte proliferation in vitro. In this study, lymphocytes from ovalbumin (OVA)-immunized Lewis rats were cocultured with OVA plus KC or adherent splenocytes from syngeneic rats injected i.v. with GD or saline. Whereas small numbers of either hepatic or splenic untreated macrophages enhanced lymphocyte proliferation, both macrophage populations treated with GD were markedly inhibitory. Neither the presence of lymph node macrophages nor of normal KC was able to prevent the effect of GD-treated KC indicating a mechanism of active suppression rather than defective macrophage antigen uptake, processing, and presentation. While cyclooxygenase inhibition had no effect, the addition of inhibitors of nitric oxide synthase, i.e., aminoguanidine and NG-methyl-L arginine, fully reversed the suppression of proliferation by GD-treated macrophages. Nitrite, but not PGE2, levels correlated with the degree of inhibition by the GD-treated macrophages. The suppression of lymphocyte proliferation and elevated supernatant nitrite levels associated with the presence of GD-treated macrophages were reversed when the macrophages were preincubated with EDTA indicating that GD's effect was directly on macrophages and due to its persistence in cultured cells. The findings of this study suggest that GD's in vivo prevention of portal venous tolerance may be due to enhanced nitric oxide synthesis whose effect on lymphocytes could be to inhibit adhesion or replication in the hepatic sinusoid. PMID- 8361166 TI - Inhibition of sarcoplasmic reticulum calcium release reduces myocardial stunning. AB - Recent findings indicate that ischemia/reperfusion (IR) is associated with phospholipase C (PLC)-induced inositol 1,4,5-triphosphate production, as well as abnormal sarcoplasmic reticulum (SR) Ca2+ release. Therefore, we hypothesized that increased SR Ca2+ release may contribute to Ca2+ overload and myocardial stunning. Neomycin (NEO) was used to inhibit PLC, and sodium dantrolene (DAN) was used to inhibit myocardial SR Ca2+ release. The purposes of this study were (1) to determine if PLC inhibition would reduce IR-induced ventricular dysfunction, (2) to examine ventricular function during inhibition of SR Ca2+ release prior to ischemia, and (3) to examine the influence of SR Ca2+ release inhibition on post IR ventricular function. Left ventricular developed pressure (DP) and +/- dP/dt of isolated crystalloid perfused rat heart (Langendorff apparatus) paced at 350 bpm were compared before and after global IR (38 degrees C, 20 min I, 40 min R) to assess functional recovery. PLC was inhibited with NEO (10 microM x 5 min prior to ischemia), and SR Ca2+ release was retarded with DAN (12.5 microM) in 0.05% DMSO (vehicle) infused for 3 min via the aortic cannula 13 min prior to ischemia. No effect on DP was observed during NEO or DAN infusion. NEO and DAN pretreatment each improved recovery of DP (% recovery +/- SEM) following IR: control, 46.5 +/- 5.1%; NEO + IR, 71.0 +/- 6.3%,* vehicle + IR, 44.4 +/- 2.9%; DAN + IR, 71.0 +/- 4.7%, *, # (*P < 0.05 vs control IR, #P < 0.05 vs vehicle + IR, ANOVA, Scheffe F test, n = 5 all groups). We conclude that SR Ca2+ release during IR contributes to myocardial stunning. PMID- 8361167 TI - In vivo hepatocyte transduction with retrovirus during in-flow occlusion. AB - Gene therapy research would be facilitated by a technically simple procedure for transducing hepatocytes in vivo. Previously reported methods have employed partial hepatectomy followed 24 hr later by asanguineous perfusion of the regenerating liver with retrovirus. We have developed a simpler method of in vivo transduction in which we deliver an intraportal bolus of retrovirus to the regenerating rodent liver during a brief period of hepatic in-flow occlusion. On Day 0, adult male Sprague-Dawley rats (N = 19) underwent 70% hepatectomy to induce hepatocyte replication. On Day 1, retroviral supernatant was harvested from an amphotropic retroviral packaging cell line that packaged an LNL6-derived vector containing the cytomegalovirus promoter driving expression of the Escherichia coli beta-galactosidase (beta gal) gene. Twenty-four hours after partial hepatectomy, experimental rats (N = 17) received 6 x 10(5) colony-forming units of retrovirus by intraportal injection during a 3-min occlusion of the hepatic artery and portal vein. Control rats (N = 2) received intraportal medium (without retrovirus), also during in-flow occlusion. The procedure required 20-25 min, and the survival rate was 84%. Cryostat sections were prepared from liver biopsies obtained on Post-transduction Days 8 and 15 and stained with 5-bromo-4 chloro-3-indolyl- beta-D-galactopyranoside to detect beta gal expression. Light microscopic examination of Day 8 sections from surviving experimental rats (N = 14) revealed 0.10-1.00% blue (i.e., transduced) hepatocytes per low power field, while sections from control rats (N = 2) exhibited no blue cells. Day 15 sections from experimental rats revealed a somewhat lower frequency of hepatocytes expressing beta gal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361168 TI - Regulation of macrophage TNF alpha, IL-1 beta, and Ia (I-A alpha) mRNA expression during peritonitis is site dependent. AB - Failure of the immune system to successfully prevent organ failure after injury or infection may be associated with a shift in macrophage function from antigen recognition and presentation to overexpression of inflammatory cytokines. Regulation may be due to changes in macrophage gene expression. Levels of mRNA for tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and the Ia subunit, I-A alpha, in peritoneal macrophages, liver, spleen, kidney, and lung were measured following cecal ligation and puncture (CLP) in Swiss Webster mice. Northern blot analysis was performed using 32P-labeled mouse cDNA probes. Peritoneal macrophage TNF alpha and IL-1 beta mRNA expression increased 2.5- and 2-fold, respectively, by 6 hr after CLP and remained elevated at 24 hr. Peritoneal macrophage I-A alpha mRNA levels decreased 8-fold by 24 hr after CLP. I-A alpha mRNA expression in liver, spleen, kidney, and lung decreased following CLP, with a return toward normal levels by 8 days in all tissues except spleen. IL-1 beta and TNF alpha mRNA were barely detectable in liver and kidney. IL-1 beta mRNA tended to increase over time in lung and spleen, whereas TNF alpha mRNA in these tissues did not vary greatly after CLP. Muramyl dipeptide or monophosphoryl lipid A pretreatment of animals prior to CLP was ineffective in altering the expression of TNF alpha and I-A alpha mRNA. We conclude that peritonitis is associated with an early increase in peritoneal macrophage TNF alpha and IL-1 beta mRNA levels and a sharp decline in macrophage I-A alpha mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361169 TI - Hypertension accelerates the growth of experimental aortic aneurysms. AB - Hypertension has long been suspected to increase the growth rate of abdominal aortic aneurysms (AAA), but there is little experimental evidence to support this hypothesis. Using an established model, aneurysms were induced in normotensive Wistar-Kyoto (WKY) rats and in a unique strain of genetically hypertensive Wistar Kyoto (WKHT) rats by perfusing an isolated segment of the infrarenal aorta with elastase (n = 14, each group). Aortic diameter was measured with a micrometer and systolic blood pressure (sBP) determined by tail plethysmography. Rats were killed at 7 or 14 days, aneurysm diameter was measured, and aneurysms were examined histologically. Systolic blood pressure was significantly higher in WKHT rats (164 +/- 15 mm Hg) compared to WKY animals (119 +/- 7 mm Hg, P < 0.001). Initial aortic size was 1.10 +/- 0.02 mm in the two groups. Aneurysms in the hypertensive animals were significantly larger at Day 7 (WKY, 2.31 +/- 0.09 mm; WKHT, 2.54 +/- 0.22 mm; P = 0.02) and Day 14 (WKY, 2.36 +/- 0.25; WKHT, 3.45 +/- 0.89; P = 0.001). Overall, the mean AAA growth rate of the WKYHT group was nearly twice that of the WKY group: 0.13 +/- 0.09 mm/day vs 0.07 +/- 0.03 mm/day, (P = 0.004). Growth rates were also positively correlated with sBP (r = 0.82, P < 0.0001). Both groups showed elastic lamellar disruption and inflammatory cell infiltration within the wall of the aorta. As demonstrated in this experimental model, hypertension does indeed increase the rate of growth of AAA. PMID- 8361170 TI - Allograft rejection by T cell receptor transgenic mice. AB - We have used a line of T cell receptor (TcR) transgenic mice, in which a significant portion of CD8+ T cells expresses a TcR that is specific for the minor histocompatibility antigen H-Y presented by the H-2Db Class I molecule, to examine the immune response to H-Y-incompatible skin or pancreatic islet allografts. Our results indicate that, in contrast to the conclusions of previous reports, pancreatic islet endocrine cells are invulnerable or only weakly vulnerable to an H-Y-directed immune response. An even more unexpected finding was that unlike normal female mice of the C57BL/6 background which consistently reject male skin within a few weeks, TcR transgene+ littermates reject male skin only infrequently. Our results are consistent with the conclusion that the inability of H-Y TcR females to reject male skin is due to a deficiency of cells with male-specific helper activity. Long-term acceptance of male grafts by H-Y TcR females leads to a state of T cell hyporesponsiveness to male skin grafts. In addition, T cells harvested from long-term skin acceptors were hyporesponsive to in vitro stimulation by a clonotype-specific monoclonal antibody. Transgenic mice with TcRs having antigenic specificity for defined transplantation antigens provide a unique model for study of the allograft response. PMID- 8361171 TI - Hypercholesterolemia and experimental vein grafts: accelerated development of intimal hyperplasia and an increase in abnormal vasomotor function. AB - Hypercholesterolemia is an important risk factor for the development of atherosclerosis. Late vein graft failure has been attributed to a combination of both intimal hyperplasia and atherosclerosis. This study examines the effect of hypercholesterolemia on the early morphology and vasomotor function of experimental vein grafts. Forty New Zealand White rabbits received either a 1% cholesterol diet (n = 24; HC) or a standard diet (n = 16; CON) for 4 weeks before operation and thereafter until harvest. All animals underwent a reversed vein common carotid artery bypass. The vein grafts and contralateral veins were harvested at 2 and 4 weeks after operation in both groups for either histological and morphometric analysis (n = 8 for each group) or for in vitro isometric tension studies using serotonin (5-HT), norepinephrine (NE), bradykinin (BK), and endothelin-1 (ET) and following NE precontraction, relaxation in response to acetylcholine (ACh) and sodium nitroprusside (SNP). Serum cholesterol levels were measured after 4, 6, and 8 weeks of the cholesterol diet. Serum cholesterol concentrations were 20 to 30 times higher than controls in the hypercholesterolemic animals at all times. The intimal area of the grafts in the HC group increased by twofold at 2 weeks and threefold at 4 weeks compared to corresponding controls. In contrast to the CON vein grafts, the intima of the vein grafts from HC consisted mainly of lipid-laden smooth muscle cells with scattered interspersed macrophages and occasional lipid plaques between the intima and the media. Medial areas were similar in all grafts. HC grafts became progressively more sensitive to 5-HT at 2 and 4 weeks. A supersensitivity to NE and BK developed at 4 weeks in HC grafts. There was no change in sensitivity to ET. While no graft relaxed to ACh, HC grafts contracted at low doses. All grafts responded to SNP in a dose-dependent manner. In contrast to CON veins, HC veins demonstrated an increase in sensitivity to NE and a contractile response to 5-HT (at 4 weeks only). HC veins did not relax in a dose-dependent manner in response to ACh. No changes in the morphology of HC veins were noted. HC produces changes in the structure and associated vasomotor abnormalities of vein grafts. Closely related functional changes also occur in contralateral veins. HC appears to induce intrinsic changes in smooth muscle cells which are linked to a greater proliferative and abnormal vasomotor capability. Clinically, applications of vigorous anti-HC regimens perioperatively may be beneficial in maintaining patency over the longer term. PMID- 8361172 TI - Effect of anti-lipid A monoclonal antibody (E5) on microcirculatory function during lipopolysaccharide shock. AB - Early septic shock is characterized by fever, increased cardiac output, decreased systemic vascular resistance, and dilation of higher-order arterioles in peripheral tissues, such as skeletal muscle. We used a rat model of low-dose lipopolysaccharide (LPS) "septic" shock to investigate the potential benefit of an anti-lipid A monoclonal antibody preparation (E5) on macro- and microcirculatory function. Twenty-five male Sprague-Dawley rats were anesthetized and instrumented for measurement of arterial pressure (AP), heart rate (HR), and cardiac output (CO). The left cremaster muscle of each rat was prepared for in vivo video microscopic examination of changes in third-order arteriolar (A3) diameter and erythrocyte velocity. Rats were randomly assigned to two groups: Group I (n = 13) received E5 vehicle and 200 micrograms/kg Escherichia coli LPS; Group II (n = 12) received 2 mg/kg E5 iv prior to LPS administration. All variables were recorded at 15-min intervals for 30 min prior to and 150 min following LPS. Microcirculatory recordings were restricted to those rats where arteriolar diameters were 20-40 microns and vessels displayed obvious vasomotion (n = 7/group). Infusion of LPS caused no significant change in AP, an increase in CO by 105 min, an increase in HR by 75 min, an increase in diameter by 75 min, and a decrease in velocity by 165 min (P < 0.01). Pretreatment with E5 inhibited the A3 vasodilation but did not affect the macrocirculatory changes. These data suggest a potential therapeutic role for E5 in ameliorating LPS-induced changes in skeletal muscle microcirculation. PMID- 8361173 TI - Blockade of prostaglandin products augments macrophage and neutrophil tumor necrosis factor synthesis in burn injury. AB - Cyclooxygenase products are believed to be a major regulator of host tumor necrosis factor-alpha (TNF-alpha) production in response to trauma and sepsis. To study this relationship, Lewis rats underwent a 30% burn or sham burn. Dimethyl prostaglandin E (dPGE, 50 micrograms/kg), ibuprofen (IFU, 2 mg/kg), or saline was administered twice daily. Rats were sacrificed at Day 7 to obtain Kupffer cells, peritoneal macrophages, splenic macrophages, and neutrophils. For in vivo studies, 10(6) cells from each group were cultured with 10 micrograms of lipopolysaccharide (LPS). For in vitro studies, cells from the burn and sham groups were cultured with LPS and dPGE (10 micrograms/ml), IBU (10 micrograms/ml), or saline. The supernatants were harvested after 2, 6, and 24 hr of culture and assayed for TNF-alpha (mu/ml) by L929 cytolysis. Burn injury resulted in a significant increase in Kupffer cell and neutrophil TNF-alpha production compared to the sham group (P < 0.001, ANOVA). The administration of IBU to burned animals led to a pronounced elevation of TNF-alpha production by Kupffer cells, peritoneal macrophages, and neutrophils compared to vehicle treated burned animals (P < 0.001, ANOVA). With in vitro studies, IBU increased Kupffer cell, peritoneal macrophage, and neutrophil TNF-alpha release by 213, 327, and 198%, respectively (P < 0.05, ANOVA). dPGE caused a marked decrease in Kupffer cell and peritoneal macrophage TNF-alpha synthesis by 50 and 43%, respectively (P < 0.01, ANOVA). In conclusion, prostaglandins are critical for down regulating TNF-alpha production. Clinical use of cyclooxygenase inhibitors may result in adverse outcomes due to the excessive TNF-alpha production. PMID- 8361174 TI - Prolongation of small bowel allografts after intrathymic injection of donor alloantigen and ALS. AB - The increasing success of clinical small bowel transplantation in recent years has been due largely to improved nonspecific immunosuppression of the recipient, which carries significant morbidity. The induction of donor-specific tolerance would eliminate the risk of long-term immunosuppression while ensuring graft function and survival. We have demonstrated that the intrathymic injection of donor splenocytes with the simultaneous intraperitoneal administration of rabbit anti-rat lymphocyte serum results in indefinite donor-specific cardiac allograft survival in > 85% of recipients. In this study, we further examined the effect of this tolerance induction protocol on the more immunogenic small bowel allograft. Male Buffalo (RT1b) rats were exposed to donor alloantigen by an intrathymic injection of 25 x 10(6) MHC mismatched unfractionated Lewis (RT1(1)) splenocytes. The Buffalo recipients were given 1 ml of rabbit anti-rat lymphocyte serum intra peritoneally at the time of the donor antigen injection and 21 days later underwent a heterotopic 15-cm Lewis small bowel transplant. Pretransplant intrathymic Lewis alloantigen and anti-rat lymphocyte serum treatment prolonged Lewis small bowel survival by approximately 2.5 times (mean survival time = 18.0 vs 7.0 days for controls, P < 0.05). These small bowel allografts demonstrated pericryptic T cell infiltrates, areas of cryptic necrosis, and a dense submucosal lymphocytic infiltrate, all consistent with acute resection. In contrast to our studies achieving donor-specific cardiac allograft survival, this protocol did not result in indefinite intestinal allograft survival. No Buffalo recipients developed evidence of graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361175 TI - Endothelial cell dysfunction occurs after hemorrhage in nonheparinized but not in preheparinized models. AB - Although hemorrhage produces alterations in hemodynamics and cellular functions, it is not known whether endothelial cell function is depressed under such conditions and, if so, whether preheparinization has any protective effect on this function. To study this, rats (with or without heparinization prior to hemorrhage, 1 U/g body wt) were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximal bleedout volume was returned in the form of lactated Ringer's solution (LR). The rats were then resuscitated with four times the volume of maximal bleedout in the form of LR. At 1.5 hr postresuscitation, the thoracic aorta was removed, cut into approximately 2.5-mm rings, and placed in organ chambers. Norepinephrine (2 x 10(-7) M) was applied to achieve near-maximal contraction, and dose responses for an endothelium-dependent vasodilator, acetylcholine, were determined. Hypoxia-induced contraction (an endothelium-dependent process) was also carried out using 95% N2:5% CO2. The results indicate that endothelium-dependent relaxation and contraction were markedly depressed following hemorrhage and resuscitation in nonheparinized, but not in preheparinized models. However, there was no significant difference in the relaxation induced by an endothelium-independent vasodilator, nitroglycerin, irrespective of heparinization. Thus, endothelial cell dysfunction (i.e., the depressed capacity of aortic endothelium to maximally release endothelium-derived relaxing and contracting factors) occurs after hemorrhage in nonheparinized, but not in preheparinized animals. Since trauma victims are not heparinized before the injury and since preheparinization protects endothelial cell function, pharmacologic agents to restore the depressed cellular function should be tested only in nonheparinized models of hemorrhage and resuscitation. PMID- 8361176 TI - Serum D(-)-lactate levels as a predictor of acute intestinal ischemia in a rat model. AB - Currently there exists no reliable serum marker for the early diagnosis of acute mesenteric ischemia. We investigated D(-)-lactate as a marker of acute mesenteric ischemia in a rat model. D(-)-Lactate is a byproduct of bacterial metabolism; it is neither produced nor metabolized by mammalian cells. In an ischemic segment of bowel the resident microflora rapidly proliferate and soon overgrow the affected intestinal segment. Additionally, the mucosal barrier of the gut begins to break down. Under these conditions we hypothesize that D(-)-lactate should cross the mucosal barrier in large quantities. To determine if this rapid bacterial proliferation and mucosal leakage produces D(-)-lactate concentrations in quantities sufficient to elevate peripheral blood levels, two models of acute intestinal ischemia and one model of simple obstruction were developed in rats. The three models included: strangulation obstruction of terminal ileum, superior mesenteric artery ligation, and simple intestinal obstruction of the ileum. Controls were divided into two groups: sham-operated controls and unoperated controls. Serum samples were collected via an internal jugular catheter at 5 min, 2 hr, and 4 hr after surgery. These samples were then assayed for D(-)-lactate using an enzymatic-spectrophotometric assay. Data was analyzed by repeated measures analysis of variance and where applicable the Student t test was used to determine statistical significance. We found statistically significant elevations in D(-)-lactate concentrations as early as t = 5 min in the strangulation obstruction model and SMA ligation model compared to unoperated controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361177 TI - Escherichia coli bacteremia exacerbates cyclosporine-induced renal vasoconstriction. AB - The clinical observation that cyclosporine (CSA) nephrotoxicity is particularly severe in patients during and following bacterial infections has recently been made. Transplant recipients develop a marked deterioration of graft function following Escherichia coli bacteremia secondary to urinary tract infection. CSA causes intrarenal vasoconstriction which may account for its nephrotoxicity. We therefore undertook a study using the split hydronephrotic kidney model to investigate the direct in vivo effects of CSA and E. coli bacteremia on the renal microcirculation. Hydronephrotic kidneys in Sprague-Dawley rats were suspended in an environmentally controlled tissue bath. Interlobular arterial (ILA) and afferent (AFF) and efferent (EFF) arteriolar diameters were measured by in vivo videomicroscopy and red cell velocity by Doppler velocimetry. Topical administration of CSA to the kidney in the tissue bath caused a 23 +/- 1% constriction of the ILA and a 67 +/- 5% reduction in blood flow. AFF and EFF arterioles were also constricted by 21 +/- 3 and 16 +/- 2%, respectively. The intravenous infusion of live E. coli was also followed by decreases in ILA diameters and flow (38 +/- 4 and 68 +/- 4%) and AFF diameters (22 +/- 5%) while EFF diameters were unchanged. The infusion of E. coli following addition of CSA to the tissue bath resulted in a dramatically increased constriction of ILA (49 +/- 4%) and AFF (31 +/- 2%) vessels and almost abolished ILA flow (90 +/- 2%). We conclude that in this model, E. coli bacteremia exacerbates CSA-induced preglomerular vasoconstriction and suggests a scientific basis for the severe renal dysfunction noted in transplant recipients during bacterial infection. PMID- 8361178 TI - Reduced ileal taurocholate absorption with total parenteral nutrition. AB - Total parenteral nutrition is associated with decreased primary bile acid output. This may result from reduced synthesis or decreased absorption of primary bile acids in the enterohepatic circulation. Ileal atrophy occurs with total parenteral nutrition, and we postulated that absorption of primary bile acids is reduced. Ileal absorption of taurocholate was investigated in miniswine on total parenteral nutrition and this was compared to orally fed animals. Following cholecystectomy and bile duct cannulation, 20 cm, of ileum was perfused with taurocholate. Since miniswine have no significant endogenous taurocholate secretion, the measured taurocholate output reflected ileal absorption. To examine uptake and secretion of taurocholate by the liver, pigs on total parenteral nutrition and controls were infused with intravenous taurocholate (0.5 to 2.5 mumole/kg/min), and bile acid output was determined. Baseline bile acid output was decreased in animals on total parenteral nutrition, yet the response to intravenous taurocholate was similar to controls. When taurocholate was perfused in the ileum, taurocholate output was markedly different. Taurocholate output (pmole/cm ileum/min) at the taurocholate perfusate concentrations of 3 and 20 mM was, respectively, 65 +/- 14 and 183 +/- 63 for controls and 18 +/- 3 and 63 +/- 17 for miniswine on total parenteral nutrition. The latter group's output was significantly lower, at P < 0.05. Both groups of pigs had equal increases in bile acid output with intravenous infusion of taurocholate, suggesting normal hepatic uptake and secretion. Ileal perfusion with taurocholate, however, resulted in decreased taurocholate output with total parenteral nutrition due to decreased ileal absorption of bile acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361179 TI - Pulmonary vascular disease and operative indications in complete atrioventricular canal defect in early infancy. AB - Pulmonary vascular disease was morphometrically analyzed in 67 patients (mean age, 19 months) with isolated complete atrioventricular canal defect. Complete obstruction of the small pulmonary arterial lumen resulting from acute fibrous proliferation and atrophy of the peripheral arterial media, which were considered absolute operative contraindications, were characteristic in six patients with Down's syndrome. Morphometric analysis of medial thickness revealed that thinning of the media of the small pulmonary arteries is generally observed at around 6 months of age in patients with complete atrioventricular canal defect and that the media in patients who have complete atrioventricular canal defect and Down's syndrome was thinner than that in such patients without Down's syndrome. These results suggest that thinning of the media as a result of two factors--Down's syndrome and aging--facilitates the rapid occurrence of fibrous intimal proliferation. Therefore intracardiac repair is desirable within 6 months of life, before medial thinning, in patients with complete atrioventricular canal defect and Down's syndrome. Excluding patients with absolute operative contraindications, the scores of the index of pulmonary vascular disease in operative survivors were below 2.0 and death occurred when scores were more than 2.2. The pulmonary vascular resistances measured in room air and by the oxygen inhalation and tolazoline tests in patients with operative contraindications were more than 7.3, 3.8, and 6.6 units.m2, respectively. We thus conclude that lung biopsy should be undertaken for patients in whom pulmonary vascular resistance is beyond these values to determine the appropriateness of surgical intervention. PMID- 8361180 TI - Contractility of the human internal mammary artery at the distal section increases toward the end. Emphasis on not using the end of the internal mammary artery for grafting. AB - The distal section of the internal mammary artery (3 to 4 cm proximal to the bifurcation) is often used for coronary grafting. This part of the artery is more pharmacologically responsive to vasoconstrictor agents than is its midsection. The present study was designed to test the hypothesis that the reactivity of the distal section of the internal mammary artery is inversely correlated to the diameter of the artery. The distal section of the human internal mammary artery was collected from aorta-coronary bypass grafts and studied in organ baths at a length of 3 mm. At the optimal point of the length-tension curves determined by a computer-iterative fitting technique, the diameter at 100 mm Hg, the maximal contraction forces and effective concentration causing 50% of the maximal response to vasoconstrictor agents U46619, potassium chloride, alpha-adrenoceptor agonists norepinephrine, methoxamine, and phenylephrine were recorded or calculated. The maximal relaxation and 50% response to glyceryl trinitrate in phenylephrine-precontracted internal mammary artery segments were also calculated. The contraction force was standardized by the circumference (grams per millimeter). Regression analysis between contraction force and diameter revealed that the contraction force induced by U46619 and potassium chloride was inversely correlated to diameter (r2 = 0.2, p < 0.05 in U46619-induced contraction and r2 = 0.2, p < 0.01 in potassium chloride-induced contraction). The contraction force induced by norepinephrine also had a trend inversely correlated to diameter (r2 = 0.2, p = 0.07). Glyceryl trinitrate-induced relaxation was not correlated to diameter. This study demonstrated that the contractility of the distal section of the internal mammary artery is inversely correlated to the diameter; that is, the smaller the diameter, the greater the tendency for spasm to develop. This suggests that trimming off the distal end of the internal mammary artery as much as possible may be the best way to prevent graft spasm and that superior results of left internal mammary artery grafted to the left anterior descending artery or the use of a "free graft" may be related to the shorter length (distal end is trimmed off) and less contractility of the graft. PMID- 8361181 TI - In vitro comparison of bileaflet aortic heart valve prostheses. St. Jude Medical, CarboMedics, modified Edwards-Duromedics, and Sorin-Bicarbon valves. AB - The hydrodynamic performance of four currently used bileaflet heart valve prostheses (St. Jude Medical, CarboMedics, modified Edwards-Duromedics, and Sorin Bicarbon) with a nominal tissue anulus diameter of 27 mm were measured in the aortic position. All experiments were performed in nonpulsatile flow and in an electrohydraulic, computer-controlled pulse duplicator simulating the left side of the human circulatory system. Testing conditions were set at cardiac outputs of 3.0, 4.5, 6.5, and 8.0 L/min at a constant heart rate of 70 beats/min. The Sorin-Bicarbon valve had the lowest pressure difference with regard to nonpulsatile (mean 5.4 mm Hg at 30 L/min) and pulsatile (mean 2.2 mm Hg at 8 L/min) flow, followed by the St. Jude Medical, CarboMedics, and modified Edwards Duromedics valves. The leakage volumes under static and pulsatile flow conditions were lowest for the modified Edwards-Duromedics and Sorin-Bicarbon valves. The energy loss in pulsatile flow was lowest for the Sorin-Bicarbon valve, mainly because its systolic, closure, and leakage energy losses were low. Systolic sequential velocity profiles showed the most even flow distribution pattern for the St. Jude Medical and Sorin-Bicarbon valves. These findings correspond with lower overall Reynolds shear stress levels for the St. Jude Medical and the Sorin Bicarbon valves than for the modified Edwards-Duromedics and CarboMedics valves. PMID- 8361182 TI - Early open mitral commissurotomy: long-term results. AB - It has frequently been suggested that early mitral commissurotomy could improve long-term results in patients with severe mitral stenosis. However, the real advantages of this procedure have yet to be demonstrated. To evaluate this hypothesis, we retrospectively studied 397 patients who underwent operation for mitral stenosis in our unit between 1978 and 1988. Forty of these patients (group I) fulfilled the criteria for early mitral commissurotomy: being young (average age 33 years), being asymptomatic or showing few symptoms, and being in sinus rhythm. The remaining 357 patients who underwent operation during the same period of time served as control (group II). Mitral valve replacement (p < 0.05) and associated tricuspid annuloplasty (p < 0.05) occurred less frequently in patients from group I than it did in patients from group II. Survival after 11 years for patients with early mitral commissurotomy was 100%, 90% of whom were in functional class I, were in sinus rhythm, and were receiving no medication whatsoever. Ninety-six percent of these patients were free of complications after 11 years, compared with 73% of patients in group II (p < 0.05). In our opinion, these results support the use of early mitral commissurotomy for young patients in sinus rhythm, who are symptom free, who are and who have a mitral valve area is 1.3 cm2 or less. PMID- 8361183 TI - Replacement of the thoracic aorta with collagen-impregnated woven Dacron grafts. Early results. AB - We used the collagen-impregnated woven double-velour Dacron graft in 120 patients undergoing 122 aortic reconstructions. Seventy-nine aortic root, ascending, or arch replacements were performed during cardiopulmonary bypass with or without circulatory arrest; 53 of the 79 were for acute aortic dissection. In addition, three infants and one child underwent repair of truncus arteriosus. There were no deaths caused by hemorrhage or bleeding-related complications. For aortic root replacement, the impervious nature of the collagen-impregnated woven double velour Dacron graft allowed elimination of wrap-around techniques. Eight deaths occurred as a result of multisystem organ failure, which followed late diagnosis of type A dissection. Two patients underwent reoperation for late complications of type A dissection. Thirty-nine patients underwent treatment for disease of the descending aorta; eight of these patients underwent a central cannulation technique with profound hypothermic cardiopulmonary bypass. The other 31 underwent repair with aortic crossclamping without bypass. Four of these patients died: two as a result of multisystem organ failure, one as a result of uncontrolled bleeding from the native dissected aorta, and one as a result of intestinal necrosis. Follow-up studies for 2 months to 5 years revealed three late deaths caused by the rupture of a persistent aneurysmal false lumen after type A dissection. The intraoperative advantages of the collagen-impregnated woven double velour Dacron graft represent an important advance in vascular graft technology. Its handling and suturing characteristics are excellent, and the graft is completely impervious in its originally manufactured state. Needle holes self-seal rapidly. Medium-term follow-up by clinical, angiographic, computed tomographic, and magnetic resonance imaging techniques showed no late graft complications--specifically, no dilatation or thrombus formation. PMID- 8361184 TI - Lining of viable and nonviable allogeneic and xenogeneic cardiovascular tissue with cultured adult human venous endothelium. AB - With the aim of creating a confluent endothelial lining of cultured adult human saphenous vein endothelial cells on cardiovascular bioprosthetic tissues in vitro, we performed seeding on deendothelialized segments of viable or devitalized (in deionized water) human vein, porcine aorta, and bioprosthetic tissues preserved in glutaraldehyde. After being seeded, specimens were kept for 7 days under culture conditions. On glutaraldehyde-preserved tissue, seeding was performed after 3 weeks of elution of glutaraldehyde. Evaluation was performed with hematoxylin-eosin staining, immunohistochemical staining of von Willebrand's factor and of collagen IV-related antigens, and scanning and transmission electron microscopy. The origin of the cells as derived from culture was verified by vital staining with a carbocyanine dye. Evaluation revealed a confluent lining of cultured human saphenous vein endothelial cells similar to native endothelium on both viable and nonviable human and porcine tissues. Collagen IV-related immunoreactivity was demonstrated close to the endothelial cells, corresponding to a de novo-formed basement membrane. Organelles and a basement membrane were demonstrated by transmission electron microscopy. The human saphenous vein endothelial cells seeded on glutaraldehyde-preserved tissues showed initial adherence but rounded up and detached on the second day of culture, probably because of residual glutaraldehyde. This study demonstrates that the native endothelium of allogenic or xenogeneic viable and nonviable vascular tissue may be replaced by cultured endothelium in vitro. The structural similarities with a native endothelium suggest that in vitro endothelialization with cultured autologous endothelial cells may be used to improve performance of cardiovascular bioprostheses. PMID- 8361185 TI - Clinical significance of weight difference between donor and recipient in heart transplantation. AB - A standard and important criterion for donor acceptance is to match the donor's body weight to within 20% of the recipient's body weight. However, to meet the increasing demand of patients who need heart transplantation, frequently a heart that is below the standard criteria for donation is accepted. Of the 200 consecutive patients who underwent heart transplantation at the University of Arizona, 27 patients received a heart from a smaller donor with a weight difference of more than 30% (range 30% to 46%). The early mortality and late survival of these 27 patients were not different when compared with those of the patients who received transplants from donors with a weight difference of less than 30%. The probability of freedom from rejection and infection and postoperative ejection fraction were also similar between the two groups. Therefore, we believe that the widely accepted donor-recipient weight-match criterion of 20% can be safely extended. PMID- 8361186 TI - Aspects of lung transplantation that contribute to increased severity of pneumonia. An experimental study. AB - In lung or heart-lung transplant recipients, complications as a result of pulmonary infections continue to be the most frequent causes of morbidity and mortality. This study was undertaken to identify the contributions of (1) thoracotomy, (2) interruption of lymphatic vessels and bronchial arteries, (3) transplant procedure, (4) drug-induced immunosuppression, and (5) graft allogenicity to the increased risk of pneumonia in lung transplantation. Lewis rats were inoculated with 10(5) colony-forming units of Legionella pneumophila serogroup 1 by direct instillation into the trachea after one of the following: a general anesthetic with no operation; a left thoracotomy; a left thoracotomy with pulmonary hilar stripping; an isogeneic orthotopic left lung transplant with or without immunosuppression; or an allogeneic transplant with immunosuppression with Brown-Norway rats as donors. Immunosuppression was induced with an intramuscular injection of cyclosporine (25 mg/kg of body weight) from the inoculation day to day 3. All rats were killed on day 6, and severity of infection was determined by quantitative culture of Legionella organisms in the lungs and spleen, titer of Legionella urinary antigen, differential cell count in bronchoalveolar lavage fluid, body weight loss, and gross inspection of the lung. Significant increases in lung Legionella concentration occurred as a result of the addition of pulmonary hilar stripping (from 10(5.13 +/- 0.34) in the thoracotomy group to 10(5.66 +/- 0.25) in the thoracotomy with hilar stripping group, p = 0.013) and the addition of immunosuppression (from 10(5.47 +/- 0.47) in the isogeneic transplant group to 10(6.94 +/- 0.52) in the isogeneic transplant with immunosuppression group, p = 0.00016). Thoracotomy, transplant procedures, and allogenicity itself resulted in no significant increases. The results for all other indicators paralleled those for lung culture. We conclude that the combination of drug-induced immunosuppression with lung denervation and interruption of lymphatic vessels and bronchial arteries results in the early development and increased severity of pneumonia in lung transplantation. PMID- 8361187 TI - Myosin light chain efflux after heart transplantation in infants and children and its correlation with ischemic preservation time. AB - Serum levels of cardiac myosin light chain 1 after heart transplantation were studied in 24 infants and children who underwent heart transplantation between June 1990 and April 1991. The ages of the patients ranged from 4 days to 6 years 7 months (mean, 9.9 months), and their body weights ranged from 2.2 to 20 kg (mean, 5.6 kg). The ages of the donors ranged from 2 days to 8 years, 7 months (mean, 26.6 months), and their body weights ranged from 2.5 to 26 kg (mean, 11.4 kg). The donor heart ischemic time ranged from 90 minutes to 482 minutes (mean, 279 minutes). Peak myosin levels after heart transplantation showed significant correlation with the duration of graft ischemia (p < 0.01) and with diastolic cardiac function in the first posttransplant week (p < 0.05). Peak myosin levels did not correlate with systolic cardiac function, age of the donor, or age of the recipient. Myosin levels of the 15 patients with graft ischemic times exceeding 4 hours averaged 6.30 +/- 3.50 ng/ml. These levels were significantly higher than those of patients with graft ischemia lasting less than 4 hours (2.60 +/- 1.20 ng/ml; p < 0.01). Both of the values are higher than previously reported values of normal controls but lower than previously reported values of patients with myocardial infarction. Preservation techniques used for this series of transplant operations provided good clinical protection of the donor heart for up to 8 hours, although release of the cardiac myosin light chain fragment correlated with duration of graft ischemia. Cardiac myosin levels appeared to be a good indicator of heart graft damage during ischemic preservation. It remains to be determined at what level of myosin release (and, hence, at what duration of graft ischemia) irreversible myocardial damage, which might result in permanent functional compromise, occurs. PMID- 8361188 TI - Early experience with sequential bilateral lung transplantation. AB - We performed 20 sequential bilateral lung transplantation in 19 consecutive patients from April 1990 to May 1992. Perioperative mortality was low (2 patients). One-year actuarial survival was 70%. All survivors had normal blood oxygen tension (82 mm Hg, mean) while breathing room air and continuing improvement of pulmonary function. Bronchial dehiscence did not occur. Stents were implanted in 7 patients to control bronchial stenosis. Aggressive treatment of graft rejection has been effective in preventing obliterative bronchiolitis. PMID- 8361189 TI - Complement activation during extracorporeal circulation. In vitro comparison of Duraflo II heparin-coated and uncoated oxygenator circuits. AB - The degree of complement activation during cardiopulmonary bypass is considered a valuable parameter of biocompatibility of the extracorporeal circuit. In an in vitro setting with a heart-lung machine primed with fresh whole blood and saline solution, the C3 activation products C3b, iC3b, and C3c and the terminal complement complex were measured in double-antibody enzyme immunosorbent assays. No differences were found between seven sets treated with Duraflo II heparin coating and seven uncoated sets after 2 hours of circulation. C3 activation products (expressed as median and 95% confidence intervals) increased from 4.5 AU (2.8 to 12.3 AU) to 16.5 AU (10.0 to 19.4 AU) in the uncoated sets (p = 0.02) and from 4.6 AU (2.2 to 5.8 AU) to 19.3 AU (3.5 to 27.1 AU) in the coated sets (p = 0.02). Terminal complement complex increased from 5.7 AU (2.7 to 11.3 AU) to 13.6 AU (8.2 to 17.8 AU) in the uncoated sets (p = 0.02) and from 7.9 AU (4.6 to 11.4 AU) to 17.3 AU (9.4 to 35.1 AU) in the coated sets (p = 0.02). A significant drop in thrombocyte levels was observed in both coated and uncoated sets. In a supplementary series, the sterilization process did not influence the results. Although Duraflo II heparin coating is considered highly effective in preventing coagulation, it did not prevent complement activation in the present in vitro study. We hypothesize that the mode by which the heparin molecule is bound to the surface may be essential to obtain effects on both coagulation and complement system. PMID- 8361190 TI - Increased plasma levels of endothelin-1 after cardiopulmonary bypass in patients with pulmonary hypertension and congenital heart disease. AB - The plasma level of the potent vasoconstrictor endothelin-1 was measured in children who underwent cardiac operations. Forty-five patients were divided into two groups, those with a high pulmonary blood flow (HF group; n = 23) and those with a normal or low flow (NF group; n = 22). Seven blood samples were taken: immediately before cardiopulmonary bypass, immediately after removing the aortic cross-clamps, immediately after discontinuing bypass, and at 20 minutes and 3, 6, and 24 hours after termination of bypass. The plasma levels of endothelin-1 were similar in both groups before bypass. From the time the aortic crossclamps were removed, the plasma endothelin-1 levels in both groups increased significantly, to reach a peak level at 3 to 6 hours. The increase was significantly greater in the HF than in the NF group, and the maximum values in the two groups were 12.6 +/- 1.1 and 9.6 +/- 0.8 fmol/ml, respectively (mean +/- standard error of the mean, p < 0.05). The value 20 minutes after bypass showed a positive correlation with the mean pulmonary arterial pressure measured at the preoperative cardiac catheterization study (r = 0.41, p < 0.05). In addition, a significant positive correlation was obtained between endothelin-1 3 hours after bypass and the maximum pulmonary/systemic arterial pressure ratio during the first 12 hours after operation (r = 0.86, p < 0.05). These results suggest that cardiopulmonary bypass is associated with an immediate postoperative increase in circulating endothelin and that patients who had a high pulmonary blood flow before the operation are particularly vulnerable, bypass having a more injurious effect on a lung with preexisting endothelial dysfunction. A high level of circulating endothelin may predispose to pulmonary vascular lability and pulmonary hypertensive crises in the postoperative period. PMID- 8361191 TI - Altered pulmonary microvascular reactivity after total cardiopulmonary bypass. AB - Pulmonary vascular resistance is frequently elevated after cardiac operations in which cardiopulmonary bypass is used. In our study of the possible contribution of altered pulmonary microvascular reactivity to this condition, sheep were heparinized, cannulated via the aorta and right atrium, and placed on total cardiopulmonary bypass. After 90 minutes of total cardiopulmonary bypass and pulmonary arterial occlusion, the sheep were removed from cardiopulmonary bypass, and their lungs were perfused normally for 60 minutes. Noninstrumented animals were used as controls. To evaluate the effect of 90 minutes of extracorporeal circulation without reduced pulmonary perfusion, we studied additional sheep after they underwent right heart bypass with a pump-oxygenator. Pulmonary microarterial vessels (130 to 230 microns in diameter) from each group were examined in vitro in a pressurized (20 mm Hg), no-flow state with video microscopic imaging and electronic dimension analysis. After preconstriction of vessels with the thromboxane A2 analog U46619 by 30% to 40% of the baseline diameter, vasoactive drugs were applied extraluminally. Serotonin caused control microvessels to dilate. In the presence of the nitric oxide synthetase inhibitor NG-methyl-L-arginine, this was converted to a significant contractile response. Acetylcholine alone had minimal effect on control vessels. However, in the presence of the cyclooxygenase inhibitor indomethacin, acetylcholine caused a significant relaxation response. After total cardiopulmonary bypass and pulmonary reperfusion, pulmonary microvessels contracted significantly when exposed to acetylcholine and serotonin, compared with respective control responses. Both these contractile responses were inhibited in the presence of indomethacin. Endothelium-independent responses to sodium nitroprusside and U46619 and dilation responses to adenosine were not altered after cardiopulmonary bypass. Extracorporeal circulation with continued pulmonary arterial perfusion (right heart bypass group) had no effect on microvascular responses. In conclusion, total cardiopulmonary bypass with associated reduced pulmonary perfusion causes significant alterations of endothelium-dependent pulmonary microvascular responses because of the increased release of a constrictor prostanoid substance and possibly because of reduced release of endothelium-derived relaxing factor. PMID- 8361193 TI - Role of amino acids and enhancement cardioplegia in routine myocardial protection. Experimental results. AB - The purpose of this study was to determine the effects of the addition of amino acids to blood cardioplegic solution and the value of terminal cardioplegia enhancement techniques in routine myocardial protection. Forty-five open-chest adult dogs were instrumented with sonomicrometry crystals to measure left ventricular long axis, midequatorial short axis, and wall thickness. The aorta was clamped for 120 minutes of cardiopulmonary bypass. Animals were randomly separated into four myocardial protection groups: (1) blood cardioplegic solution with amino acids and no terminal cardioplegia (n = 12); (2) blood cardioplegic solution with amino acids and warm amino acid terminal cardioplegia (n = 11); (3) blood cardioplegic solution with amino acids and cold amino acid terminal cardioplegia (n = 12); and (4) blood cardioplegic solution plus cold terminal cardioplegia (no amino acids, n = 10). Data for preload recruitable stroke work were obtained by inflow occlusion before bypass (baseline) and at 30 and 60 minutes after reperfusion and analyzed for changes in x-intercept and slope. A significant rightward shift in x-intercept did not occur in any group. When cardiac function was expressed as a percentage of baseline preload recruitable stroke work slope, improved functional recovery was seen at both 30 and 60 minutes in groups 2 (88.6% and 91.8%), 3 (85.8% and 86.9%), and 4 (88.6% and 92.6%) compared with group 1 (77.3% and 79.2%, p < 0.05). No significant difference was found in the degree of functional recovery among groups 2, 3, and 4. These results suggest that for myocardial protection of 2 hours in nonischemic hearts, a terminal dose of blood cardioplegic solution before unclamping is beneficial, but this positive effect is independent of amino acid supplementation and temperature. PMID- 8361192 TI - Blockade of cyclosporine-induced vasoconstriction by the calcium channel blocker diltiazem in dogs. AB - The calcium channel blocker diltiazem has been shown to reduce cyclosporine toxicity both in clinical and in experimental studies. To determine the effect of diltiazem administration on cyclosporine vasoconstriction and on renal release of endothelin, we administered cyclosporine in models of renal and hind limb autoperfusion in the dog. Infusion of cyclosporine in the hind limb (20 mg) during diltiazem perfusion caused an average increase of 6 +/- 2 mm Hg in hind limb perfusion pressure compared with 17 +/- 2 mm Hg before diltiazem, a significant difference (p < 0.05). Similarly, injections of cyclosporine (10 mg) in the kidney during diltiazem infusion caused an average increase of 26 +/- 4 mm Hg in renal perfusion pressure compared with 83 +/- 13 mm Hg before diltiazem infusion, a significant decrease in the renal vascular response (p < 0.05). On the other hand, sodium nitroprusside did not change the renal vasoconstriction to cyclosporine, which suggests a specific effect of diltiazem. Serum levels of endothelin in renal venous blood increased from 0.5 +/- 0.4 pg/ml to 3.8 +/- 0.6 pg/ml with cyclosporine, despite diltiazem infusion. Therefore, although the calcium channel blocker diltiazem effectively decreases cyclosporine-induced renal and hind limb vasoconstriction, it does not act by preventing endothelin release induced by cyclosporine stimulation. PMID- 8361194 TI - Cardioplegic effect of University of Wisconsin solution on hypothermic ischemia of rat myocardium assessed by mitochondrial oxidative phosphorylation. AB - The effectiveness of the University of Wisconsin solution and the Collins' M solution for preservation of rat hearts was compared by examining histologic appearance, tissue water content, and mitochondrial respiratory functions after prolonged hypothermic storage and subsequent heterotopic transplantation. Survival of transplanted hearts after 5 days of reperfusion was markedly lowered by storage in Collins' M solution for 15 hours. Hearts stored in University of Wisconsin solution for 10 hours showed no increase in myocardial necrosis after 5 days of reperfusion, whereas hearts stored in University of Wisconsin solution for 15 hours and Collins' M solution for 10 and 15 hours showed a significant increase in tissue necrosis. University of Wisconsin solution reduced tissue swelling during hypothermic storage, whereas Collins' M solution did not cause such reduction. The yield of mitochondrial protein after reperfusion was significantly decreased by storage in either solution, especially after 15 hours in Collins' M solution. Mitochondrial oxidative phosphorylation was significantly inhibited by storage, especially by storage in Collins' M solution and subsequent reperfusion. These results indicate that myocardial injury, after prolonged ischemia and reperfusion, results in a decrease in functionally and structurally intact mitochondria that is dependent on preservation conditions. University of Wisconsin solution protects isolated hearts against ischemia and reperfusion injury possibly by preventing cellular and mitochondrial deterioration. PMID- 8361195 TI - Duration of asystolic reperfusion and reperfusate electrolyte composition influence postcardioplegia ventricular fibrillation. AB - The conditions of postcardioplegia reperfusion that influence cardiac electrophysiologic recovery have not yet been fully elucidated. Studies of postcardioplegia electrophysiologic recovery and reperfusion-induced arrhythmias, particularly reperfusion-induced ventricular fibrillation, are useful for improving our understanding of reperfusion injury since reperfusion-induced arrhythmias are sensitive indicators for reperfusion injury. The purpose of this study was to determine the effects of asystolic reperfusion and reperfusate electrolyte composition on postcardioplegia electrophysiologic recovery of the heart. The hypothesis tested is that the duration of asystolic reperfusion produced by a hyperkalemic reperfusate is a primary determinant for the return of cardiac electrical activity without reperfusion-induced ventricular fibrillation and that reperfusion with a hypocalcemic-hyperkalemic solution further reduces the prevalence of reperfusion-induced ventricular fibrillation by limiting myocyte calcium exposure during initial postischemic recovery. Fifty-six pigs were supported by cardiopulmonary bypass and subjected to identical conditions of hypothermic cardioplegic arrest. Reperfusion was initiated with unmodified pump blood, a hypocalcemic-normokalemic cardioplegic solution, a hyperkalemic normocalcemic cardioplegic solution, or a hyperkalemic-hypocalcemic cardioplegic solution. The hyperkalemic-normocalcemic solution was administered at a dose of 500 ml/m2 or 1500 ml/m2. The hyperkalemic-hypocalcemic and hypocalcemic normokalemic solutions were given only at a dose of 500 ml/m2. All cardioplegic reperfusion solutions were followed by infusion of unmodified pump blood for the remainder of the 15-minute period of controlled reperfusion. Reperfusion-induced ventricular fibrillation was less prevalent in the high-dose hyperkalemic solution group (4/12) than in the low-dose hyperkalemic solution (9/10) or unmodified pump blood (12/12) groups (p < 0.05). The transmyocardial lactate gradient at the time of initial postreperfusion electrical activity was positive (0.21 +/- 0.04 mmol/L) in the high-dose hyperkalemic group and negative (-0.05 +/ 0.09 mmol/L) in the low-dose hyperkalemic group (p < 0.05). Fibrillation was less prevalent in the hypocalcemic-hyperkalemic group (8/12) than in the other groups reperfused with cardioplegic solution at a dose of 500 ml/m2 (hypocalcemic normokalemic, 10/10; hyperkalemic-normocalcemic, 9/10) or in the group reperfused with unmodified pump blood (12/12) (p < 0.05, hypocalcemic-hyperkalemic group versus other reperfusate groups). Reperfusion-induced ventricular fibrillation is an indicator of reperfusion injury, and in this study the conditions of reperfusion influenced the prevalence of reperfusion-induced ventricular fibrillation. Recovery of aerobic metabolism during hyperkalemia-induced asystolic reperfusion was associated with a lower prevalence of reperfusion induced ventricular fibrillation. Combining hypocalcemia with hyperkalemia decreased the prevalence of reperfusion-induced ventricular fibrillation. PMID- 8361196 TI - Multivariate analysis of risk factors for thrombus formation in University of Tokyo ventricular assist device. AB - Of 77 University of Tokyo ventricular assist devices used in a total of 70 patients at 21 institutions, 13 pumps were found to have macroscopic thrombus formations. Because 19 devices that were used for less than 24 hours showed no thrombus deposition, they were considered not to have been sufficiently exposed to the thrombogenic environment for macroscopic thrombus deposition and were removed from the subsequent multivariate study. A total of eight potential risk factors were assessed in relation to thrombosis. Prevalences of thrombus formation were compared between two groups with or without each of the risk factors. In a univariate analysis, the following categoric variables were demonstrated to be significantly associated with complications, in descending order of significance: use of gabexate mesilate (protease inhibitor) as an anticoagulant (p = 0.005), normal platelet count (p = 0.010), duration of support (p = 0.038), leukocytosis (p = 0.042), and minimum pumping flow (p = 0.042). Use of heparin and the consequent increase in activated clotting time showed no relationship. Multivariate discriminant analysis, which was done to identify risk factors rejecting cross correlation between each variable, demonstrated platelet count (p = 0.006), use of gabexate mesilate (p = 0.007), and minimum flow (p = 0.008) to have significant and independent risks. These results indicate the importance of maintaining pumping flow above a certain minimum level, addition of antiplatelet drugs to the antithrombogenic regimen, and nonuse of gabexate mesitate. PMID- 8361197 TI - Influence of hydrogen ion concentration versus carbon dioxide tension on pulmonary vascular resistance after cardiac operation. AB - Disturbances of respiratory acid-base status are common in patients supported with mechanical ventilation of the lungs after cardiac operations. This study was conducted with two protocols. The purpose was to determine whether respiratory acid-base status influences pulmonary vascular resistance in adults after cardiac operations and whether the influence is mediated by hydrogen ion concentration or carbon dioxide tension. Patients were studied while under general anesthesia immediately after aorta-coronary bypass. In the first protocol, with seven patients, arterial carbon dioxide tension was manipulated by the addition of 5% carbon dioxide to the breathing circuit. Pulmonary vascular resistance index was determined as arterial carbon dioxide tension rose from 30 mm Hg to 50 mm Hg and back to 30 mm Hg. In the second protocol, with 10 different patients, hydrogen ion concentration was manipulated by the addition of 0.2N hydrochloric acid, sodium bicarbonate, or both as arterial carbon dioxide tension was held constant. We used analysis of variance for statistical data. The results of the first protocol showed that pulmonary vascular resistance index rose by 44% (p < 0.05) as arterial carbon dioxide tension rose from 30 to 50 mm Hg. The results of the second protocol showed that changes in pulmonary vascular resistance index were parallel to changes in hydrogen ion concentration as arterial carbon dioxide tension was held constant (p < 0.05). These data demonstrate that respiratory acid-base status is an important determinant of pulmonary vascular resistance in the adult after cardiac operations. Furthermore, these data suggest the effect is mediated by hydrogen ion concentration, not carbon dioxide tension. PMID- 8361198 TI - Endobronchial metastasis. AB - Endobronchial metastases from nonpulmonary neoplasms are rare. Since 1971, we have treated 23 patients with endobronchial metastases, the findings for which form the basis of this article. Many types of primary tumors are capable of endobronchial metastases, although breast, colon, and renal carcinomas predominate. The mean time from the diagnosis of the primary carcinoma to the diagnosis of endobronchial metastases was 59.9 months. Bronchoscopic results were diagnostic in all cases. Although the mean time for the appearance of endobronchial metastases is almost 5 years, on examination the majority of patients will have symptomatic extrabronchial metastatic disease, the quality of their survival will often be poor, and their survival time will be limited (12.5 months). Surgical resection should be confined to patients with localized disease. PMID- 8361199 TI - Chemotherapy and operation for invasive thymoma. AB - Sixteen patients with invasive thymoma (stage III and stage IVA) were treated with chemotherapy and then operation. All tumors were considered nonresectable after first staging, and patients were treated with the following chemotherapy in 4-day courses, administered intravenously: cisplatin (50 mg/m2) and doxorubicin (40 mg/m2) on day 1, vincristine (0.6 mg/m2) on day 3, and cyclophosphamide (700 mg/m2) on day 4. The courses were repeated every 3 weeks, and toxic effects were well tolerated. Seven patients (43%) had a complete remission, and nine patients (57%) had a partial remission, with an overall complete remission plus partial remission rate of 100%. After chemotherapy all patients underwent operation. We performed 12 sternotomies and four posterolateral thoracotomies. At operation 11 patients had radical resection and five had partial resection. We administered radiotherapy in 11 patients who had histologically demonstrated tumor after operation. In five patients, the specimen showed only fibrosis; these patients received three cycles of chemotherapy but not radiotherapy. Median survival was 66 months with a 3-year survival of 70%. We believe that neoadjuvant chemotherapy with surgical intervention is justified for advanced invasive thymoma; a longer follow-up and a larger number of patients will determine the impact of this treatment on long-term survival. PMID- 8361200 TI - Techniques for localization of pulmonary nodules for thoracoscopic resection. AB - Significant advances in surgical equipment, video monitoring, and endoscopic surgical techniques have expanded the role of thoracoscopy to include pulmonary resection. One limitation of the thoracoscopic technique is the loss of manual palpation to identify the nodule that is either too small or too deep beneath the pleural surface. We describe the techniques used in 300 thoracoscopic pulmonary resections that have aided in identification of pulmonary nodules. These techniques include careful preoperative assessment of the computed tomogram, preoperative injection of methylene blue, or a needle localizing system to identify the nodule. Intraoperative techniques include instrument palpation, digital palpation, and intraoperative ultrasonography. It should be possible to identify the majority of pulmonary nodules at the time of thoracoscopy with these localizing techniques. All nodules were successfully identified in our last 200 thoracoscopic resections. PMID- 8361201 TI - Thoracoscopic mediastinal lymph node sampling: useful for mediastinal lymph node stations inaccessible by cervical mediastinoscopy. AB - Cervical mediastinoscopy is useful for the diagnosis of paratracheal lymph node metastasis from bronchogenic carcinoma. Access to adenopathy in the aorticopulmonary window, anterior mediastinal, periazygos, and subcarinal lymph nodes is difficult with this technique. Operative visibility in these locations through anterior mediastinotomy, the Chamberlain procedure, is limited. We have used thoracoscopic mediastinal exploration in 40 patients with computed tomographic scan evidence of enlarged aorticopulmonary window (n = 30) or enlarged right periazygos or subcarinal lymph nodes (n = 10). This procedure was used primarily as an adjunct to cervical mediastinoscopy in the staging of bronchogenic carcinoma. Adjunctive thoracoscopic nodal sampling was 100% sensitive and 100% specific in diagnosing the mediastinal adenopathy. It did not significantly delay thoracotomy in cases of benign adenopathy. Visibility of the ipsilateral pleural space and mediastinum was excellent. Thoracoscopic exploration with mediastinal nodal sampling is a valuable diagnostic adjunct for assessment of adenopathy inaccessible to cervical mediastinoscopy and can overcome many of the limitations of anterior mediastinotomy. PMID- 8361202 TI - Invited letter concerning: what is the best therapeutic strategy for mitral stenosis? PMID- 8361203 TI - Interpretation of data on the use of 5'-nucleotidase inhibition to preserve the cardioplegically arrested rabbit heart. PMID- 8361204 TI - Anomalous origin of the left coronary artery from the pulmonary artery in older adults. PMID- 8361205 TI - Endothelium-dependent relaxation and interaction between indomethacin and L-NG monomethylarginine in coronary bypass grafts. PMID- 8361206 TI - Invited letter concerning: cytokines and mechanisms of capillary leakage after cardiopulmonary bypass. PMID- 8361207 TI - Invited letter concerning: experience with 205 procedures of transcatheter closure of ductus arteriosus in 182 patients, with special reference to residual shunts and long-term follow-up (J Thorac Cardiovasc Surg 1992;104:1721-7) PMID- 8361208 TI - A new technique to simplify the Fontan procedure after a previous bidirectional Glenn shunt. PMID- 8361209 TI - Modulation of cell proliferation and cytokine production in AML by recombinant interleukin-1 receptor antagonist. AB - In Acute Myelogenous Leukemia (AML), Interleukin 1 (IL-1) might sustain autocrine and paracrine loops of leukemic growth. An IL-1 inhibitor has been recently purified and cloned. This molecule binds to the IL-1 receptors but has no IL-1 like activity fulfilling the characteristics of a pure Interleukin-1 receptor antagonist (IL-1ra). We studied the in vitro effect of human recombinant IL-1ra on proliferation of AML blasts. Spontaneous as well as IL-1 stimulated AML proliferation was significantly inhibited by the addition of 50 ng/ml of recombinant IL-1ra in a dose dependent manner. The inhibitory effect of IL-1ra was measurable after 12 hours of culture and reached a plateau at 60 hrs. We found that IL-1ra could compete with IL-1 in binding to specific IL-1 receptors on AML cells. As expected, culture supernatants of unstimulated leukemic samples contained IL-1 beta and GM-CSF activity. The incubation of the same leukemic blasts with IL-1 ra was followed by reduction or disappearance of GM-CSF in culture supernatants whereas the IL-1 beta production was only partially modulated. By Northern blot experiments performed on freshly isolated, uncultured leukemic blasts, we found a constitutive expression of the IL-1 beta gene in 19 of 23 AML cases analyzed. On the contrary, only three of these patients express the IL-1 RA mRNA. All together these results suggest that imbalanced secretion of IL-1 and its natural receptor antagonist could contribute to the unrestricted growth of AML cells. PMID- 8361210 TI - Reconstitution of functional human GM-CSF receptor in mouse NIH3T3 fibroblasts and BA/F3 proB cells. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high affinity human GM-CSF receptor (hGM-CSFR) in a proB cell line BA/F3 by cotransfecting alpha and beta chain cDNA clones and showed that the reconstituted receptor could transduce growth promoting signals. The high affinity hGM-CSFR was also reconstituted in mouse NIH3T3 cells, but its ability to transduce signals in fibroblasts remained unanswered. In the present study, we further characterized signal transduction by the reconstituted hGM-CSFR both in NIH3T3 cells and BA/F3 cells. We found that the reconstituted hGM-CSFR transduces signals in NIH3T3 fibroblasts and BA/F3 cells in response to human GM-CSF to activate transcription of c-fos, c-jun and c-myc protooncogenes. hGM-CSF also induces protein tyrosine phosphorylation and DNA synthesis in both cell types. The ability of hGM-CSFR to transduce signals was affected by inhibitors of tyrosine kinase. These results indicated that the hGM-CSFR is functional in fibroblasts, that signal transduction via the hGM-CSFR in fibroblasts involves tyrosine kinase(s) and that association of hGM-CSFR with factor(s) specific to hematopoietic cell lineage is not essential to transduce growth promoting signals. PMID- 8361211 TI - Analysis of Pim-1 function in mutant mice. AB - The Pim-1 gene has frequently been found activated by proviral insertion in haematopoietic tumors in mice. The fact that overexpression of Pim-1 can contribute to lymphomagenesis was formally proven by overexpressing a Pim-1 transgene in lymphoid cells. The transgene induces a low incidence of T cell lymphomas and an increased susceptibility to chemically (ENU) and virally (MoMuLV) induced lymphomas. The mouse Pim-1 gene encodes two cytoplasmic protein serine/threonine kinases. Northern analysis shows the highest expression to be in haematopoietic tissues, especially early in development. High expression has also been noted in testis and ES cells. Expression can be induced by growth factors and mitogens. The gene is evolutionarily highly conserved. Inactivation of both Pim-1 alleles in ES cells or mice did not reveal any obvious abnormalities. In order to look more closely for possible haematopoietic abnormalities specific growth factor response were studied in vitro. The IL-3 response of bone marrow derived mast-cell cultures (BMMC) was found to be severely impaired in mast cells derived from Pim-1 deficient mice. PMID- 8361212 TI - Activation of the erythropoietin receptor and leukemia induction in mice. PMID- 8361213 TI - In vivo role of macrophage growth factors as delineated using CSF-1 deficient op/op mouse. AB - Total absence of CSF-1 in the op/op mouse leads to a profound and generalized deficiency of macrophages and to osteopetrosis subsequent to the absence of osteoclasts. These observations confirm that CSF-1 is a genuine regulator of macrophage and osteoclast formation in vivo. Further studies in affected animals have shown that the CSF-1 absence variably affects macrophage differentiation stages and different organ macrophage populations, and that functionally competent macrophages are produced in low numbers without CSF-1, presumably under the influence of GM-CSF and IL-3. The op/op mice have increased levels of both endogenous GM-CSF and IL-3, which apparently are not fully able to compensate for the absence of CSF-1. Macrophage deficiencies but not osteoclast deficiencies in the op/op mouse could be completely corrected by exogenous GM-CSF, while exogenous CSF-1 corrects both osteoclast and macrophage deficiencies, but only in those tissues which could be reached by CSF-1 from the circulation. Despite severe quantitative macrophage deficiencies, the op/op mice demonstrate normal in vivo phagocytosis and immune functions suggesting that CSF-1 dependent macrophages do not contribute significantly to those processes in vivo. On the other hand, the op/op mice demonstrate severe secondary deficiencies of TNF alpha, IL-1 alpha, and G-CSF suggesting that major function of CSF-1 dependent macrophages is the release of monokines. PMID- 8361214 TI - Growth factor regulation of the maintenance and differentiation of human long term culture-initiating cells (LTC-IC). AB - Current evidence suggests that the most primitive of hematopoietic progenitors detectable in adult human marrow are cells that can give rise to clonogenic cells for > 5 weeks in vitro when co-cultured with certain stromal cells. Procedures developed to isolate these so-called long-term culture-initiating cells (LTC-IC) in highly purified form allow their separation from most other hematopoietic cells as well as from stromal cells and their precursors also present in the marrow. We have used such procedures in conjunction with the LTC system to identify specific growth factors that support human LTC-IC maintenance and differentiation and to make comparisons with effects on later events in hematopoiesis. In some studies, soluble growth factors were added exogenously to the study cultures. In others, marrow-derived fibroblasts were genetically engineered to allow increased levels of specific human growth factors to be endogenously produced. In both of these ways, the influence of granulocyte- macrophage colony-stimulating factor (GM-CSF), G-CSF, Interleukin-3 (IL-3), IL-6, and Steel factor were investigated. Increased provision of GM-CSF alone (or in combination with other factors) enhanced terminal cell differentiation (production of granulocytes and macrophages), although the same conditions had no influence on LTC-IC differentiation (production of clonogenic cells) or on LTC-IC maintenance. In contrast, G-CSF, IL-3 and IL-6 alone (and more so when combined) in the presence of feeders effectively enhanced LTC-IC differentiation and was less active on later stages of granulopoiesis. Provision of additional exogenous Steel factor also enhanced LTC-IC differentiation, although Steel factor alone, without feeders or other growth factors, did not support either the initial differentiation of LTC-IC into clonogenic cells or their subsequent differentiation into mature granulocytes and macrophages. No combination of exogenously added growth factors was found that enhanced LTC-IC maintenance over that achieved with primary marrow feeders. However, some murine fibroblasts (including those of SI/SI origin), as well as certain exogenous growth factors (including Steel factor), were able to substitute for feeders in this regard. These observations highlight the likelihood of redundancy in factors that can elicit similar biological responses at the earliest as well as later stages of hematopoietic cell development. Nevertheless, it appears that the responses of hematopoietic cells at different stages of differentiation to any particular factor may differ markedly and that the nature of any particular response is not yet predictable from a knowledge of effects on earlier or later cell types. PMID- 8361215 TI - In vitro culture of bone marrow cells for autografting in CML. AB - Long-term maintenance of normal hematopoiesis in vitro is possible when very primitive progenitors are cocultivated with certain non-hematopoietic stromal cells that may co-exist in (or be derived from cells that co-exist in) hematopoietic tissues. Such long-term cultures (LTC) have been used to develop quantitative assays for the most primitive populations of hematopoietic cells currently detectable in adult marrow. In addition they provide a unique model for analysis of the complex molecular mechanisms that may regulate primitive hematopoietic cell population dynamics in vivo. Similar studies with LTC of cells from patients with chronic myeloid leukemia (CML) have made it possible to detect and characterize very primitive neoplastic cell populations in this disease. These latter studies have revealed differences in the properties of primitive CML cells that both reflect and explain their increased turnover and are thus presumably part of the mechanism that enables the neoplastic clone to expand in vivo. In addition, the most primitive neoplastic cells in CML patients are abnormally distributed between the marrow and blood and their ability to maintain their numbers in LTC has also been found to be defective. Assessment of the number and behaviour of primitive cells in LTC of CML marrow has been used to identify those patients most likely to benefit from intensive therapy supported by transplantation of cultured autologous marrow. Twenty-two such CML patients have now been treated with this experimental protocol. The results to date have clearly established the feasibility of this novel treatment strategy and, together with more recent laboratory findings, suggest future avenues for significantly improving the management of CML patients. PMID- 8361216 TI - Identification of P-glycoprotein/multidrug resistance genes from model organisms. AB - Using degenerate oligonucleotides from conserved portions of the ATP-binding domain of the active transporter genes, several new members of this gene superfamily have been cloned from Drosophila, Saccharomyces cerevisiae, and E. coli DNA. The Drosophila and E. coli genes contain two sets of transmembrane domains and two ATP-binding domains, whereas the yeast gene contains single transmembrane and ATP-binding domains. All three genes show a high degree of similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) genes. The E. coli sequence is the only known transporter gene containing both ATP and transmembrane domains in a single open reading frame. While the function of these sequences has not been determined, they may prove to be useful for developing a model to study the function of P-glycoproteins. PMID- 8361217 TI - Follow-up of the first two successive German multicentre trials for adult ALL (01/81 and 02/84). German Adult ALL Study Group. PMID- 8361218 TI - Chronic myelocytic leukemia: development of conditioning regimens for marrow transplantation. PMID- 8361219 TI - Leukaemias in Africa. AB - Until recently, cALL has been uncommon in sub-Saharan Africa, but there is now emerging a peak of incidence at the age 3 to 5 years in west and southern Africa. Prognosis for African patients with cALL is poor because of a multitude of clinical, biological and social factors. AML is seen at high frequency (probably indicating truly high incidence) in male children 5-14 years, of whom up to a quarter present with chloroma. It is predicted that the incidence of AML in adults may rise in the near future, related to cigarette smoking, occupational and environmental exposures to benzene and other pollutants, and the prescription of alkylating agents to young people with malignant disease. CML shows no particular epidemiological features, except for a high frequency in young adults and children, reflecting the age structure of the whole population. There are two forms of B-CLL: one is seen most commonly in women of low socioeconomic status towards the end of the their reproductive life, and is probably related to an initially polyclonal expansion of B-cells in response of recurrent malaria and other infections; the other is seen over the age of 45 years, with men being affected twice as commonly as women, as in the western world. PMID- 8361220 TI - Treatment results of three consecutive Brazilian cooperative childhood ALL protocols: GBTLI-80, GBTLI-82 and -85. ALL Brazilian Group. AB - The Brazilian Cooperative Group for Treatment of Childhood Acute Lymphocytic Leukemia (GBTLI) has started clinical activities trials in 1980. Three consecutive multicenter studies in children with unprevious treated ALL have been completed including 994 patients. The first GBTLI-80 accrued 203 children from 1980 to 1982. It was delineated with the standard three drugs induction therapy, CNS protection for all pts comprised cranial irradiation and intrathecal Methotrexate. For low risk pts cranial irradiation with 18Gy was compared in a randomized trial with 24Gy. Maintenance therapy continued for 120 weeks. The 12 years of the event free survival rates for all risk groups is 50% (SD 5%). Regarding CNS relapses there was no significant statistical difference between pts that received 18 or 24Gy. The treatment strategy of GBTLI-82 (n = 360) from 1982 to 1985, consisted of the same previous induction, consolidation, CNS therapy with cranial irradiation 18 Gy (low risk) or 24Gy (high risk), followed by continuous maintenance for 2 years. The main question in this study was the comparison between sequential rotation or pulses of 3 pairs of drugs during maintenance. At a median follow-up of 10 years, the overall event free survival rates for all children is 58% (SD 4%). There was no significant difference between the two maintenance regimens. The successor GBTLI-85 ran from 1985 to 1988 and registered 431 pts. For the first time no cranial radiation was given to children with very good prognosis. For them, CNS protection was done with triple intrathecal therapy during all treatment. A consolidation therapy with high dose ARA-C was introduced for high risk pts and infants The 6.5 years event free survival for all children is 70% (SD 4%). Significant better results were achieved for high risk and infants pts (EFS 50%). Early intensification therapy and rotational combination chemotherapy improved the outcome in childhood ALL in Brazil. PMID- 8361221 TI - Ethnicity and survival in children with acute lymphoid leukemia. PMID- 8361222 TI - Stem cell regulation and engraftment. PMID- 8361223 TI - 1992 Stohlman Memorial Lecture: targeting the IL-2 receptor. AB - Patients with human T-cell lymphotropic virus I (HTLV-I)-associated leukemia/lymphoma were treated with different forms of IL-2 receptor (IL-2R) directed therapy that exploit the difference in IL-2R expression between normal and malignant cells. Using unmodified anti-Tac monoclonal antibody, one-third of the patients with adult T-cell leukemia (ATL) treated have undergone a remission, in two cases complete. There was little toxicity observed; however, unmodified monoclonal antibodies are limited by their immunogenicity and their poor effector functions. To address these issues, "humanized" anti-Tac was produced that contains the complementarity-determining regions from the mouse with the remainder of the molecule derived from human IgG1 kappa. This antibody is dramatically less immunogenic than the murine version, has improved pharmacokinetics, and, in contrast to the parent antibody, manifests antibody dependent cellular cytotoxicity (ADCC). To enhance its effector function, anti Tac was armed with toxins and alpha- and beta-emitting radionuclides. In a clinical trial of 90Y-anti-Tac in ATL patients, at the doses used (5, 10, and 15 mCi 90Y-anti-Tac per patient), 10 of the 15 patients with ATL treated to date underwent sustained partial or complete remission. Thus, the clinical application of IL-2R-directed therapy represents a new perspective for the prevention of allograft rejection and for the treatment of graft-versus-host disease, select autoimmune disorders, and leukemia/lymphoma. PMID- 8361224 TI - A song in praise of peptide palindromes. AB - Peptide palindromes are invariably found in all proteins, and long palindromes exceeding 10 residues in length are not rare. They are particularly abundant in DNA-binding proteins such as H1 histone. When a complementary strand of the coding sequence is translatable being free of a chain terminator, a complementary protein encode by it becomes equally abundant in peptide palindromes. The simultaneous musical transformation of both strands of mouse H1 histone variety-1 DNA enable us to appreciate the symmetrical beauty of successive palindromes appearing in both H1 histone and its complementary protein. PMID- 8361225 TI - Hematopoietic cytokines: from biology and pathophysiology to clinical application. PMID- 8361226 TI - P53 mutations in human cancer. AB - A 53,000 dalton protein called p53, was noted to be mutated in human cancer in 1987. Further studies have shown that p53 is a tumor suppressor gene which may be one of the most frequently altered genes in cancer of all types. These alterations include interactions with viral antigens, coding mutations and inactivating rearrangements. Accumulating evidence suggests that p53 acts by binding DNA and activating transcription. Expression of p53 after transfection with a constitutive promotor, blocks cellular proliferation and leads to an apoptotic cell death. In normal cells, p53 expression is induced by irradiation; this has led to the hypothesis that p53 acts to inhibit replication during genetic repair. Cells which lack p53 are more prone to develop amplification. Mice lacking p53 are born normal but develop cancer after a lag of months, this suggests that p53 is not an initiating mutation in cancer, but probably a late event. PMID- 8361227 TI - The mitogenic response of AML blasts to tumor necrosis factor-alpha requires functional c-jun/AP-1. AB - The c-jun proto-oncogene belongs to the family of immediate early response genes and is inducible by serum growth factors and Tumor Necrosis Factor (TNF). In the present study we have addressed the role of c-jun for the mitogenic response of primary acute myelogenous leukemia (AML) blasts to TNF-alpha. Our data indicate that TNF-alpha treatment of these cells is associated with transcriptional activation of c-jun and accumulation of c-jun mRNA. In order to elucidate the role of c-jun for TNF-mediated growth stimulation, an antisense (AS) oligomer directed towards the translation initiation site of c-jun was instrumental. Uptake studies of oligonucleotides showed that incorporation of oligomers was maximal at 4 hours. Oligodeoxynucleotides remained stable in these cells for up to 24 hours. Treatment of AML blasts with the AS oligonucleotide resulted in intracellular duplex formation followed by efficient translation blockade of c jun/AP-1. In contrast, sense (S) and none-sense (NS) oligodeoxynucleotides failed to form intracellular duplexes and also did not interfere with translation of c jun/AP-1, suggesting specific elimination of c-jun/AP-1 by the AS oligomer. AML blasts cultured in the presence of AS to c-jun, but not of S or NS, failed to proliferatively respond to TNF-alpha stimulation. Taken together, our results indicate that activation of c-jun/AP-1 plays a pivotal role in the signaling cascade initiated by TNF which leads to a proliferative response of its target cells. PMID- 8361228 TI - Stromal regulation of hemopoiesis and the role of subliminal growth factor production. PMID- 8361229 TI - p53 protein expression in Reed-Sternberg cells of Hodgkin's disease. AB - Hodgkin's disease (HD) is perceived to be a malignant disease of the lymphoid system. One of the main obstacles into the investigation of the cell biology of Hodgkin's disease is the relative paucity of Reed-Sternberg cells (or variants), the presumed neoplastic component of this condition, which often make up less than 1% of the total cell number. PMID- 8361230 TI - The isolation of a yeast artificial chromosome which spans the chromosome 11q23 region involved in a number of translocations in acute leukaemias. PMID- 8361231 TI - T cell development: new approaches. AB - The differentiation of T lymphocyte precursors into functionally mature progeny proceeds in distinct stages. Since these are identified by characteristic constellations of phenotypic markers, the effects of experimental manipulations on T cell development can be readily monitored. In order to complete their developmental program, thymocytes must interact with stromal elements, which positively and negatively select the functional T cell receptor (TCR) repertoire. This process normally assures self tolerance and immunocompetence. Disturbances are of practical importance for clinical disorders including immunodeficiencies and autoimmune phenomena, raising a particular interest in human T cell development and repertoire formation. Here, we discuss results and possible applications of a culture system for human thymocytes. Further, we describe an in vitro approach addressing the requirements for a crucial step in T cell development; the transition from the immature CD4 CD8 double positive (DP) to the mature CD4 single positive (SP) stage. PMID- 8361232 TI - Ligand-induced apoptosis of mature T lymphocytes (propriocidal regulation) occurs at distinct stages of the cell cycle. AB - We previously demonstrated that mature T lymphocytes responding to either IL-2 or IL-4 undergo apoptosis upon T cell antigen receptor stimulation, and have termed this potential negative feedback pathway propriocidal regulation. Using cell cycle inhibitors, we now show that T cell growth lymphokines cause the entry of T cells into vulnerable stages of the cell cycle in which T cell receptor occupancy causes apoptosis. PMID- 8361233 TI - Memory and the lifespan of human T lymphocytes. AB - The properties of human CD45RA and CD45R0 T cells are described. CD45R0 cells respond to recall antigens and provide help for B lymphocytes. They produce a wide variety of cytokines including IL-2, IL-4 and IFN-gamma. CD45RA T cells respond poorly to recall antigens and produce mainly IL-2. The phenotype of CD45R0 cells suggests that they may be in cycle and in vivo data shows that they have a short lifespan while CD45RA cells are long lived. The lineage relationship of the two subsets is not clear but in vivo and in vitro evidence suggests bidirectional conversion between CD45RA and CD45R0 phenotypes. PMID- 8361234 TI - Regulation of human T cell receptor beta gene expression by Ets-1. AB - Expression of the human TcR beta gene is controlled by an enhancer located 6kb 3' to the C beta 2 gene segment. The activity of this enhancer has been shown to be inducible with phorbol esters. Within the enhancer the beta E2 element is responsible for the major part of the inducibility, multimerised beta E2 alone is also highly phorbol ester inducible. The beta E2 element contains a consensus ets binding site as well as a core motif, and we have shown that the beta E2 ets site binds both Ets-1 and Ets-2 in vitro and that purified core binding factor (CBF) can bind the core site present in beta E2. Mutations which specifically disrupt Ets-1 and Ets-2 binding abolish inducibility as well as reducing activity, whereas mutants which cannot bind CBF have only reduced basal activity. In Jurkat, which has a high level of endogenous Ets-1, multimerized beta E2 was inactive unless treated with PMA. However when transfected into cells with no detectable Ets-1 the beta E2 multimer was highly active in the absence of PMA. Co transfection of an Ets-1 expression construct with the full enhancer into Jurkat cells led to a repression of enhancer activity, suggesting a repressive role for Ets-1. Co-transfection of Ets-1 was also able to repress strongly the activity of the beta E2 multimer. Repression of activity from both the full enhancer construct and the beta E2 multimer was most dramatic in the presence of PMA, suggesting that Ets-1 could block TcR beta activation. The Ets-1 expression construct used transactivated the HTLV-1 LTR which has also been shown to bind Ets-1. The repression of beta E2 activity by Ets-1 appears therefore to be specific. In conclusion, the combination of ets and core sites in beta E2 constitutes a novel inducible element, which is specifically transrepressed by Ets-1. PMID- 8361235 TI - Studies of HIV-2 promoter activity and cell specific ablation. AB - We have a developed a retroviral mediated molecular ablation method to specifically eliminate HIV Tat-expressing cells. This approach utilizes the Tat inducible HIV-2 promoter and a conditional toxin gene. The Herpes Simplex Virus thymidine kinase gene product is toxic to mammalian cells only after treatment with Ganciclovir (GCV) or other nucleoside analogues. We demonstrate here that certain promoter modifications can decrease basal expression while retaining the ability to be transactivated. Furthermore, we show that a HIV-2 promoter thymidine kinase gene cassette transduced via retroviral vectors into tissue culture cells can specifically promote the ablation of HIV-Tat expressing cells in the presence GCV. We also show that there is a large differential in HIV thymidine kinase gene transcription and lethal drug dose between Tat-expressing cells and Tat-negative cells. PMID- 8361236 TI - Lymphoproliferative disorders in an IL-7 transgenic mouse line. AB - A high incidence of severe lymphoproliferative disease was observed in a newly generated strain of mice carrying murine IL-7 as a transgene under the control of the E alpha (MHC class II) promoter. An analysis of the cells from lesions in these mice shows the selective expansion of cells at an early stage of B cell development and, more interestingly, expansion of cells phenotypically identical to the recently reported bipotent (B/macrophage) stem cell populations described in midgestation embryonic liver. Such cells can be propagated (and remain dependent upon) bone marrow feeder cell lines obtained from IL-7 transgenic mice. A molecular analysis of fresh and cultured cells reveals that the lesions are oligoclonal, or in rare cases monoclonal, and include clones of cells with unrearranged Ig heavy chain loci. These data suggest that IL-7 acts at multiple stages of B cell development. Furthermore cell lines derived from IL-7 transgenic mice may provide a novel source of rare factor-dependent bipotent stem cells. PMID- 8361237 TI - Recent approaches to induction of cytotoxic lymphocytes against leukemia. AB - We have shown that therapy of AML patients in second remission with continuous infusion of IL-2 resulted in generation of cytotoxic lymphocytes in peripheral blood and bone marrow. However, these lymphocytes mediated cytotoxicity only against tumor cell lines, and not against AML blasts. Additional in vitro activation with higher dose of IL-2 was necessary for induction of AML blast oncolysis. This indicates that the concomitant treatment with continuous and periodic bolus IL-2 infusion may be necessary, to achieve higher levels of IL-2 and subsequently, more potent lymphocyte activation. Alternatively, it may not be possible to induce optimal antileukemia response in vivo with tolerable doses of IL-2, and the adoptive therapy with in vitro supremely activated lymphocytes may represent an option. In this article, we discuss several approaches to the supreme activation of cytotoxic lymphocytes against highly resistant AML blasts and their possibilities in leukemia therapy. PMID- 8361238 TI - Natural history of HTLV-I infection: relationship to leukemogenesis. PMID- 8361239 TI - Adult Day Health Care Evaluation Study. PMID- 8361240 TI - Implications of the Adult Day Health Care Evaluation Study for program revision and research. AB - With no additional effort to revise adult day health care (ADHC) services or the types of patients who receive them, it would appear that adding an ADHC program to a VA Medical Center would not achieve the desired objectives. The authors discuss here the advantages, disadvantages, and feasibility of 2 options for program revision. The first is to target ADHC to those types of patients who may be most likely to benefit. A targeting scheme should use the most objective criteria possible and may need to be implemented as part of a case-managed package of community-based services. The second option for program revision is to reduce the costs of ADHC services. A cost model developed as a part of the study demonstrated the effect of possible revisions, including increasing enrollment, reducing staffing costs, decreasing length of stay in ADHC, and increasing substitution of ADHC for other services. These changes differ in the level of administrative support and clinician behavior change needed for their implementation. This report then concludes with a discussion of the implications of the results for implementation of VA-ADHC versus contract ADHC, and a discussion of possible directions for future research. PMID- 8361241 TI - The Adult Day Health Care Evaluation Study--impact on VA programs. AB - The research study in Adult Day Health Care (ADHC) has had a fourfold impact on the Veterans Administration: 1) It defined the health care focus of ADHC and shaped consequent program design; 2) It forged a partnership between research and clinical staff in ADHC programmatic development; 3) It enhanced the perception of research in program development in long-term care; and 4) It provided VA with direction for program redesign to render ADHC more cost-effective. With careful planning, the program is expected to grow in the future as a part of VA's continuum of long-term care programs. PMID- 8361242 TI - One more battle lost to friendly fire--or if you spend too much it's hard to save money. PMID- 8361243 TI - Program implications of the Veterans Adult Day Health Care studies. PMID- 8361244 TI - Data collection in the Adult Day Health Care Evaluation Study. AB - This report presents data collection measures and methods for the evaluation of Adult Day Health Care (ADHC) in the Department of Veterans Affairs (VA). Measures of patient health were survival, the Sickness Impact Profile, self-rated health, the Mini-Mental State Exam, Psychological Distress Scale, Social Support Scale, and Problem Behaviors Scale. Measures of health for the care giver were: Activities of Daily Living, Instrumental Activities of Daily Living, health perceptions, Psychological Distress Scale, life satisfaction, Social Support Scale, and Caregiver Burden Scale. We also assessed patient and care giver satisfaction with the care received by the patient. Measures of health status and outcomes were assessed primarily through patient and care giver interview at study enrollment, 6 months, and 12 months. Utilization and cost both within and outside VA were assessed for hospital, ambulatory care, nursing home, ADHC, home care, pharmacy, laboratory, and other forms of health care. Sources of utilization data included VA's computerized patient database, VA medical records, patient questionnaires, care giver questionnaires, and health care providers outside VA. Costs were obtained from VA's cost accounting system, VA Central Office, VA's contracts with outside providers, and directly from outside providers. Utilization and cost were assessed for each patient for a period of 1 year after entry into the study. PMID- 8361245 TI - Adult day health care organizational and program characteristics. AB - A survey of 31 adult day health care (ADHC) programs assessed the extent to which the programs were implemented as intended by the VA. The study described and compared the host communities, ADHC organizational characteristics, program characteristics, and patient use of services. Four of the centers were operated by the Department of Veterans Affairs in VA Medical Center facilities. The remaining 27 centers were community providers serving veterans on contract through four additional VA Medical Centers. Veterans Administration programs were located in larger facilities, with lower client/staff ratios and fewer hours of operation than community contract programs. Patients on the average made 45 visits to the VA-ADHC programs and 58 visits to the contract ADHC programs. The VA and contract programs were generally found to have been implemented as planned, i.e., they followed VA guidelines for staffing, space, and equipment. PMID- 8361246 TI - Overview and patient recruitment in the Adult Day Health Care Evaluation Study. AB - Although Adult Day Health Care (ADHC) is increasingly prominent in the continuum of long-term care services, the results from previous studies of the effects of ADHC are mixed. The objectives of the ADHC Evaluation Study were to determine the effect of ADHC on health status, utilization, and cost of care. The first phase was a randomized controlled trial evaluating ADHC provided directly by the VA. Patients at four medical centers (n = 826) were randomly assigned to receive either ADHC or customary care, and outcomes were compared for the two groups. The second phase was a prospective cohort study evaluating ADHC provided under contract to community agencies in which patients at four additional medical centers (n = 163) were assigned to contract ADHC programs. Outcomes were compared with those of similar patients in the randomized trial. Patients and care givers were assessed at intake and 6 and 12 months after intake. To be admitted to the study, patients must have met one of the following criteria: residence in a nursing home; dependence in ambulation, dressing, or toileting; bowel incontinence; or significant cognitive impairment. Patients at intake demonstrated major impairment in function and high levels of prior use of health care services. PMID- 8361247 TI - Effects of VA adult day health care on health outcomes and satisfaction with care. AB - It was hypothesized that ADHC would have a positive effect on the health of patients and their care givers and result in greater satisfaction with care than customary care. Measurement of health outcomes for patients included assessment of overall, psychological, and social health, and survival. Care giver assessment concentrated on psychosocial health. Findings indicated no difference in health outcomes between patients assigned to ADHC or their care givers and their counterparts assigned to customary care. Further analysis of subgroups found that there were 3 subgroups of patients for whom those assigned to ADHC had better outcomes (as indicated by lower Sickness Impact Profile scores) than those assigned to customary care. These subgroups included those who were 1) not married, 2) most satisfied with their social support network, and 3) not hospitalized at the time of enrollment in the study. Patients and their care givers assigned to ADHC were more satisfied with their care than those in nursing homes, but not more satisfied than those in hospital-based home care. Care givers reported significantly greater satisfaction with patient care in ADHC than did care givers of patients receiving care in nursing homes or ambulatory care clinics. PMID- 8361248 TI - Cost of VA adult day health care programs and their effect on utilization and cost of care. AB - The VA-ADHC Evaluation included a detailed assessment of the cost of the VA-ADHC programs and an evaluation of their effect on patients' utilization and costs of other health care services. Although each VA-ADHC program had little variation in its program costs over the 3 years of the study, there were large variations between the programs in total costs, their costs per patient day, and in some cost components. The 3 most important factors in determining the level of program costs were: the way patients were transported to and from ADHC, the availability of space to house the program, and the staff-to-patient ratio. The total cost of health care for patients randomly assigned to VA-ADHC was significantly (15.5%) higher than those assigned to customary care. Although ADHC care did substitute for certain other forms of care (i.e., home care and clinic visits), there was not enough of a substitution effect to offset the additional costs of ADHC services. PMID- 8361249 TI - Effects of adult day health care on utilization and cost of care for subgroups of patients. AB - An important goal of the Adult Day Health Care (ADHC) Evaluation Study was to identify subgroups of patients assigned to ADHC for whom the health care costs were less than, or not higher than, the costs of similar patients assigned to customary care. Patients eligible for VA services because of a severe disability that occurred during military service had significantly lower costs when assigned to ADHC compared with customary care. For several types of patients, total health care costs were not significantly higher for those assigned to ADHC compared with those assigned to customary care: patients who at study intake 1) were at highest risk of going to a nursing home, 2) had high levels of physical dysfunction as measured by the Sickness Impact Profile, 3) had multiple behavior problems, and 4) were eligible for VA services because of a less severe service-connected disability but admitted to the ADHC for treatment of that disability. Two types of patients were found to have particularly high costs when assigned to ADHC compared with customary care: patients with low levels of physical dysfunction and patients with few behavior problems. Significant differences in the relative costs of ADHC versus customary care also were found between the 4 study sites. PMID- 8361251 TI - Comparison of utilization and cost among contract adult day health care, VA adult day health care, and customary care. AB - The contract ADHC evaluation compared the utilization and costs of patients assigned to contract ADHC with patients assigned to VA-ADHC care or customary care in the VA-ADHC evaluation. The ADHC costs per patient day were lower on average in the contract sites than in the VA-ADHC sites, although they were similar to the costs at 2 of the 4 VA-ADHCs. The contract site patients received significantly more days of ADHC care, offsetting their lower cost per day. Contract site patients had significantly fewer VA clinic visits and VA nursing home admissions than did patients in the VA-ADHC or customary care groups. Patients at the contract sites also had significantly fewer days of nursing home care than did the customary care group patients. Propensity scores based on intake characteristics were used to adjust for initial differences between the patients in the 2 evaluations. After adjustments, the total cost of care for contract ADHC patients was found to be significantly higher than the cost for customary care patients, but no significant difference was found between contract ADHC patients and VA-ADHC patients. PMID- 8361250 TI - Effects of contract adult day health care on health outcomes and satisfaction with care. AB - The second phase of the ADHC Evaluation Study was designed to assess ADHC provided under contract by community ADHC programs. Outcomes for the 163 patients enrolled in this prospective cohort evaluation were compared with those of patients assigned to ADHC provided directly by VA (VA-ADHC) and customary care in the randomized trial phase of the study. In spite of identical admission criteria, contract ADHC patients were significantly different from VA-ADHC and customary care patients on several characteristics and were more impaired in health status at study intake. They were also more impaired in physical health status at 12 months, even after controlling for baseline differences. There were no significant differences in any other patient or care giver health outcomes. Contract ADHC patients were more satisfied than customary care patients in nursing homes (but not more satisfied than patients in home care), whereas VA ADHC patients were more satisfied than those in contract ADHC. It is suggested that differences in physical function are due to differences in patient health status at intake rather than a detrimental effect of contract ADHC. PMID- 8361252 TI - Summary and discussion of methods and results of the Adult Day Health Care Evaluation Study. AB - This article summarizes the study results and presents an evaluative summary of the implementation of study methods designed to provide guidance in the degree of confidence with which the results may be accepted and generalized to other situations. Patients who were offered VA-ADHC services in the first phase of this study had significantly higher VA health care costs on average than patients assigned to customary care, with no apparent incremental health benefit to themselves or their care givers. One can have a high level of confidence in these results. The ADHC clinical services were implemented as planned, the randomized controlled trial was implemented successfully, and such threats to validity as insufficient numbers of patients and differential attrition were not present. Certain subgroups of patients assigned to VA-ADHC had VA costs of care that were not significantly higher than those assigned to customary care, although these results must be interpreted with caution. The findings of the second phase of the study evaluating contract ADHC provide no support for choosing to provide either contract ADHC or VA-ADHC over the other. The nonrandomized design and smaller sample size suggest that inferences from the contract ADHC evaluation should be drawn with more caution than those from the VA-ADHC evaluation. PMID- 8361253 TI - The fifth Paul Ehrlich Lecture, Virus strains as models of molecular evolution. PMID- 8361254 TI - Biotechnology in the drug discovery process: strategic and management issues. PMID- 8361255 TI - Stability of liposomal doxorubicin formulations: problems and prospects. PMID- 8361256 TI - Opportunistic/nosocomial infections. Treatment and developmental therapeutics. I. Cryptococcosis. PMID- 8361257 TI - Standards of clinical investigations in the USA. AB - The drug approval process in the USA is under constant surveillance, monitoring and evaluation. Several significant changes were made during the past few years and many others are under consideration. The FDA has undergone organizational changes, which together with the IND Rewrite and NDA Rewrite resulted in a shift of emphasis in clinical studies. PMID- 8361258 TI - The development of good clinical practice in the EEC and in Germany. AB - In 1965 the first EEC Directive on the approximation of the national provisions related to medicinal products (65/65/EEC) stipulated, beside others, that the application for registration shall contain results of clinical trials. Ten years later Directive 75/318/EEC ensured uniform standards and protocols for the performance of test and trials, especially clinical trials. In May 1987 the CPMP Recommended Basis for the conduct of clinical trials addressed the general norms and scientific principles for the conduct, performance and control of clinical trials of medicinal products. Based on 75/318/EEC and on CPMP Recommended Basis, intensive discussions continued in order to further improve the measures to thoroughly protect the rights and integrity of the trial subjects, to establish the credibility of data, and to improve the ethical, scientific and technical quality of trials. As a result of these negotiations CPMP adopted in 1990 the note for guidance: GCP for Trials on Medicinal Products in the EC. In July 1991 Directive 91/507/EEC modifying 75/318/EEC was issued. It adopts the requirements to prove quality, safety and efficacy to the latest state of the art. The German Drug Law (AMG) from 1976 transposed 65/65/EEC in its substantial parts. AMG contains its own section called "Protection of the human being during the clinical trial", which only stipulates a list of general conditions to be fulfilled before starting the trial. In Dec. 1987 German Health Ministry (BMG) published a paper on the orderly execution of clinical trials to establish rules on the planning, execution, evaluation and documentation of clinical trials (BMG Principles).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361259 TI - Status of the GCP guidelines in Europe. AB - Two key factors are of main importance for the development of a common GCP legislation in the Member States of the European Community: 1) July 1991, Enforcement of the EEC Note for Guidance: "Good Clinical Practice for Trials on Medicinal Products in the European Community". This enforcement was setting into operation GCP guidelines which were, however, not yet legally binding at that time. 2) January 1992, Enforcement of EEC Commission, Directive 91/507/EEC: Analytical, pharmacotoxicological and clinical standards and protocols in respect of the testing of medicinal products. By this enforcement the EEC Member States were obliged to bring into force the laws, regulations and administrative provisions necessary to comply with the Directive which requests--besides others- all clinical trials to be designed, implemented and recorded in accordance with GCP. Facing the different national regulations covering clinical trials already being in force at that time, some of the European countries are considered to already be in compliance with EEC-GCP. In other countries, however, the Directive causes situations in which EEC-GCP is more demanding than the existing legislation or even contradictory. Country by country this has to be regulated soon by appropriate measures of the legislators in order to establish a uniform standard which will assure clinical trials to be internationally acceptable. Only recently the CPMP introduced the requirement for a "Compliance with GCP" Statement as an indispensable part of the Clinical Expert Reports in registration documentations. Even more than in legislation, there is a lack of inspections in clinical trials by health authorities in most European countries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361260 TI - Inspection of clinical investigations by the German health authorities. AB - Based on the regulations of the German Drug Law of 1976 (Arzneimittelgesetz, AMG) the inspections of clinical investigations by the competent health authorities focus on the protection of the human being taking part in the trial. Standards for the planning, methodology, conduct, report and documentation of clinical trials are laid down in a guideline (Grundsatze fur die ordnungsgemasse Durchfuhrung der klinischen Prufung, Dec. 1987), a kind of national GCP standard which has to be respected by sponsors, physicians and authorities, not only for inspection but also for drug registration. PMID- 8361261 TI - Experiences with GLP/GCP from the pharmaceutical industry's viewpoint. AB - The European Commission Directive 91/507/EEC has been enforced since January 1, 1992. It requires that all trials of a clinical development program be performed in compliance with Good Clinical Practice (GCP) guidelines which became effective on July 1, 1991 after approval by the CPMP in July 1990. Good Laboratory Practice (GLP) guidelines originated in the USA in 1978 and have been adopted in general in the OECD guidelines (OECD principles of Good Laboratory Practice, 1983) and in the appropriate national laws and guidelines, e.g., Chemikaliengesetz vom 14.3.1990, Germany. All GLP guidelines unambiguously address "non-clinical laboratory studies", for example, toxicological studies but not studies utilizing human subjects. The impact/non-impact of these guidelines is addressed by the day to-day work in a clinical pharmacology unit within the pharmaceutical industry. PMID- 8361262 TI - Good clinical practice and phytotherapy. AB - The GCP Guideline of the European Community on the performance of clinical trials became obligatory in June 1991. As the GCP standards have mainly been set for innovative drugs, there is a certain danger that these criteria could not be fulfilled by medicines used in phytotherapy. As regards, the chances and risks of the European guideline, especially for herbal medicines, the differences between chemically-defined and herbal drugs, as well as the extent, to which herbal medicines might be concerned by the guideline, have to be taken into account. Herbal medicines are different from chemically defined medicines in their character as well as in their medicinal use. They always contain a mixture of numerous substances. Data on preclinical investigations are often incomplete, whereas, on the other hand, physicians and patients have a long-term experience in applying these medicines. They are, in general, well-tolerated and therefore suitable for the treatment of chronic diseases. Due to a characteristic taste and smell, the production of placebos is often impossible. The GCP directive also contains basic elements concerning chemically defined drugs as well as herbal medicines in a similar way. PMID- 8361263 TI - [Occupational health services in the future. Elimination or transformation?]. PMID- 8361264 TI - [District physicians working together are transformed into competing family physicians]. PMID- 8361265 TI - ["Giraffe language"--new "high-class" medical terminology?]. PMID- 8361266 TI - [Evaluate new methods!]. PMID- 8361267 TI - [Take a popular vote on euthanasia!]. PMID- 8361268 TI - [Dynamic psychotherapy has its place both in clinical work as well as in education]. PMID- 8361269 TI - [Surgeons: register complications!]. PMID- 8361271 TI - [Preventive vitamin K and childhood cancer. A Swedish study shows no connection]. PMID- 8361270 TI - [Therapeutic alternatives in acute cerebral embolism]. PMID- 8361273 TI - [Attitudes to condoms and knowledge about STD. An inquiry among patients at a department of veneorology]. PMID- 8361272 TI - [Do ACE inhibitors potentiate snake venom? Severe and prolonged hypotension caused by adder bite]. PMID- 8361274 TI - [Prevention of stroke. Blood pressure lowering changes in life style and diet are highly effective]. PMID- 8361275 TI - [X-ray findings in persons seeking asylum. Diagnosis and follow-up are important]. PMID- 8361276 TI - [Early discharge from maternity wards. Medical safety for the child and the family is achieved by follow-up visits]. PMID- 8361277 TI - [Practical handling of bacterial meningitis. Mortality and sequelae can be dramatically influenced]. PMID- 8361278 TI - [Corticosteroids in bacterial meningitis. An old therapeutic principle with new interest]. PMID- 8361279 TI - [A new drug against heart failure was retracted after an alarm about increased mortality]. PMID- 8361280 TI - [Cancer panorama prior to the next century. Doubled number of living cancer patients]. PMID- 8361281 TI - [How should the reduced health resources be distributed? Prioritization must be discussed]. PMID- 8361282 TI - [Successful therapy and analysis of mechanisms. Prestigious prizes to cancer researchers]. PMID- 8361283 TI - Multichannel (Ineraid) cochlear implant update. AB - From April 1984 to May 1991, 49 profoundly deaf patients received implantation of the Ineraid multichannel cochlear implant at the University of Utah. The auditory results of 48 patients indicated improvement in mean pure-tone performance to 500 Hz (32.9 +/- 10.1 dB), 1000 Hz (27.1 +/- 10.0 dB), and 2000 Hz (30.1 +/- 9.8 dB). This group of patients had mean performances of 61.2% on auditory-only environmental sounds (Minimum Auditory Capabilities [MAC] battery), 48.8% on auditory-only CID sentences, and 95.5% on auditory-plus-visual CID sentences. The percutaneous pedestal has been well-tolerated. Changes in the surgical skin incisions have been made. A home use speech therapy program has been developed on VHS tapes. PMID- 8361284 TI - Acute epiglottitis in the adult: experience with a seasonal presentation. AB - Acute epiglottitis in adults may follow an unpredictable clinical course, complicated by acute airway obstruction. Our experience with this disease was evaluated by looking at yearly incidence, seasonal occurrence, and clinical variables of both intubated and conservatively managed patients. In our series of 17 cases from 1987 through 1990, 16 occurred in 1988 and 1989. Ten of 17 cases occurred during the summer months. The two patients who developed stridor went on to require intubation and tracheotomy. Statistical analysis of our data revealed that, in adult acute epiglottitis, stridor is a strong predictor of airway obstruction. A significant summer seasonal predominance was seen, as well as a suggestion of an epidemic in 1988 and 1989. PMID- 8361285 TI - Hashimoto's thyroiditis and carcinoma of the thyroid: optimal management. AB - Several authors have noted a high incidence of thyroid carcinoma in patients with Hashimoto's thyroiditis (HT), and some have even considered HT a premalignant condition. The authors evaluated all patients with surgically proven HT at Beth Israel Medical Center in New York from 1985 through 1990. Of these 48 patients, 8 (17%) had thyroid carcinoma in addition to HT. No statistically significant difference between patients with and without concurrent carcinoma was noted in the percentage of patients with a dominant mass, irregular thyromegaly, compressive symptoms, suspicious fine needle aspiration biopsies (FNABs), or a cold nodule on thyroid scintigraphy. However, patients with neither a positive FNAB nor a cold nodule were much less likely to have carcinoma than patients with one or both of these tests positive (0% vs. 26%, P < or = .05). A management scheme for patients with HT is proposed to adequately and efficiently evaluate and treat patients for concurrent thyroid carcinoma. PMID- 8361286 TI - Contact diode laser microvascular anastomosis. AB - Contact diode laser microvascular anastomosis appears to be a valuable technique for anastomosing small arteries and veins. Significantly less foreign body reaction and markedly decreased operative time has been shown to be a major advantage of using contact diode laser technology. The authors have found that contact diode laser anastomosis can be performed in vessels as small as 1 mm in size using a 200-microns flat tip synthetic sapphire probe. Light microscopy has shown a significant decrease in foreign body reaction at the level of the anastomosis using laser techniques as compared to standard vessel anastomosis with 10-0 nylon sutures. The role of fibronectin and changes in collagen associated with laser anastomosis were also explored. Light microscopic electron microscopic results as well as biotin-avidin immunoperoxidase fibronectin studies will be discussed. PMID- 8361287 TI - Nodal size of metastatic squamous cell carcinoma of the neck. AB - The preoperative use of computed tomographic (CT) scanning continues to be the best diagnostic method for preoperative detection of metastatic neck disease. Current accepted criteria for CT diagnosis of nodal disease are not uniform, although nodal size, nodal grouping, and central necrosis correlate strongly with malignancy. To assess the relationship of nodal size and malignancy, a multicenter study was designed to evaluate the nodes from 100 neck dissections. Sixty-nine positive neck dissections were analyzed, and every node was measured. The relationship of central necrosis was also compared with node size. Our results showed that CT scanning continues to provide a reliable picture of the histologic status of lymph nodes. Using the criterion of central necrosis or node size larger than 1 cm, only 7% of necks had nodal disease that would have been missed by CT interpretation. This study supports the continued use of preoperative CT evaluation for metastatic neck disease. PMID- 8361288 TI - Orthotopic laryngeal transplantation: is it time? AB - The notion of returning phonatory and respiratory function by transplanting larynges has fascinated and challenged the minds of laryngologists for many years. In the past, the problems of revascularization, tissue rejection, and physiologic vocal fold motion have stymied the success of research in this area. Today, advances in microvascular surgery, graft versus host response, and selective reinnervation have made laryngeal transplantation a theoretical, if not a practical reality. Despite this progress, serious ethical and fiscal considerations remain unresolved. This report will discuss these advances as well as concerns and will present the current UCLA laryngeal physiology laboratory experience with canine laryngeal transplantation. PMID- 8361289 TI - Localization of glucocorticoid receptors and glucocorticoid receptor mRNAs in the rat cochlea. AB - The distribution of glucocorticoid (GR) receptor messenger RNAs (mRNAs) and GR receptors was studied by in situ hybridization histochemistry and immunocytochemistry, respectively. In situ hybridization histochemistry was performed with a biotin-labeled riboprobe complementary to rat GR receptor mRNA. GR receptor mRNAs were demonstrated in spiral ligament cells, spiral limbus cells, and spiral ganglion cells. GR receptor mRNAs were demonstrated neither in cells of the stria vascularis nor in cells of the organ of Corti region. With the use of a monoclonal and a polyclonal antibody, GR receptors were observed in the spiral ligament cells, stria vascularis cells, spiral limbus cells, and spiral ganglion cells by immunocytochemistry. Binding of anti-GR-receptor antibodies to a lesser extent was observed in the organ of Corti region; however, cellular distribution of the GR receptors could not be resolved with the applied techniques. These results suggest that the GR receptor is expressed differently in the heterogeneous cochlear tissues. PMID- 8361290 TI - A methodological study of hemilaryngeal phonation. AB - An excised hemilarynx setup was developed. The phonatory characteristics of nine excised canine larynges were examined. The left vocal fold of each larynx was then removed and substituted with a vertical plexiglass plate. The larynges were phonated again. Recordings were made of phonation threshold pressure, sound pressure level, average glottal flow, fundamental frequency, and amplitude of vocal fold vibration as observed with a video stroboscope. Measurements were made over a range of subglottal pressures. For the hemilarynx, simultaneous recordings of intraglottal pressure and vocal fold contact area were also made. It was found that amplitude and frequency of vocal fold vibration of the hemilarynx, as well as rates of change of amplitude and frequency as a function of subglottal pressure, were similar to those of the full larynx. Also similar were phonation threshold pressures and ranges of subglottal pressure over which the larynges phonated. The average airflow of the hemilarynx was approximately half that of the full larynx, and the sound pressure level, under similar conditions, was one fourth (about 6 dB less) in the hemilarynx. PMID- 8361291 TI - Use of bone for obliteration of the nasofrontal duct with the osteoplastic flap: a cat model. AB - The management of the frontal sinus remains controversial for traumatic and inflammatory disease. The osteoplastic flap with fat obliteration has become the treatment standard, although late failures with infection and mucocele formation may arise. Theories for mucocele formation include regrowth of residual mucosa from the sinus and ingrowth of mucosa from a nonobliterated nasofrontal duct. A study to evaluate the means of nasofrontal duct obliteration was developed. Three cat groups were evaluated at 1, 2, and 3 months. Group 1 had the duct and sinus obliterated with fat. Group 2 had the duct obliterated with bone and the sinus with fat. Group 3 had only the duct obliterated with bone. There was no mucosal ingrowth in any of the sinuses for the intervals studied. In group 1, fat volume was seen to decrease over time with replacement by fibrous tissue within the duct. Groups 2 and 3 developed progressive obliteration of the duct with new bone formation. One may infer that fat obliteration alone does not provide a predictable stable situation as fat atrophies within the duct and may allow mucosal ingrowth. Bone obliteration was shown to be progressive within the duct from osteogenesis. This is the first experimental model to correlate clinical observations of the use of bone for sinus obliteration. This study concluded that bone obliterates the nasofrontal duct better than the accepted standard of fat, independent of the material used to obliterate the sinus. PMID- 8361292 TI - Functional endoscopic surgery in children: a retrospective analysis of results. AB - The impact of chronic sinusitis on children has become more apparent as the awareness of the disease has increased. Consequently, the knowledge of its effect in the pediatric patient has expanded dramatically. Functional endoscopic sinus surgery (FESS) has become the primary surgical modality for treatment of this illness in children who have not responded to optimal medical management. A retrospective study was conducted in patients from 7 months to 17 years of age who were treated with FESS for chronic sinusitis refractory to medical therapy. Using a comprehensive parental questionnaire and a review of the medical charts, results were analyzed from these post-FESS children. Parents of the children were interviewed with a mean follow-up time of 21.8 months postoperatively. Factors discussed included chronic nasal obstruction, purulent nasal discharge, postnasal drip, chronic cough, halitosis, headaches, behavioral problems, allergies, and asthma symptoms. This preliminary investigation suggests that FESS is effective in treating medically recalcitrant severe chronic sinusitis in children. PMID- 8361293 TI - Microbial colonization of Blom-Singer prostheses in postlaryngectomy patients. AB - The microbial colonization of 44 Blom-Singer valves obtained from 16 patients over an 11-month period was investigated both by standard microbial culture methods and scanning electron microscopy (SEM). The valves were all removed from the patients after failure to function correctly. The microbiology cultures revealed that Candida species and Staphylococcus aureus were present either individually or in combination on 43 valves. SEM showed yeast hyphae attached to and penetrating the surfaces of the 5 valves examined. Colonies of staphylococci were also seen on 2 of these 5 valves. Unlike similar investigations on other voice prostheses, S aureus colonization was associated with Candida colonization and valve failure. PMID- 8361294 TI - Nasal airway size in cleft and noncleft children. AB - Although the effects of cleft lip and palate on nasal airway size and breathing have been reported for adults, little information is available on children. The present study assessed the effect of age on nasal cross-sectional size and, in particular, whether type of cleft influenced the outcome. The results indicate that, while the cleft nose continues to grow with age, it remains about 30% smaller than the noncleft nose. The airway is smallest in patients with unilateral cleft lip and palate and is largest in those with bilateral clefts. The prevalence of oral breathing is considerably higher in the cleft population in comparison to noncleft. PMID- 8361295 TI - Snoring and nasal resistance during sleep. AB - Although it is widely accepted that nasal obstruction leads to snoring and sleep apnea, the relationship between these variables is not clear, mainly because of the lack of studies in which nasal resistance (Rna) and snoring were measured concurrently. The authors studied eight nonapneic snoring men with healthy noses by nocturnal polysomnography that included quantitative assessment of snoring and concomitant nasal resistance. In six of these eight patients nasal resistance increased during sleep, but there was no significant change for the group as a whole between wakefulness (0.209 +/- 0.224 Pa/cm3 per second) and sleep (0.292 +/ 0.203 Pa/cm3 per second). Linear regression analysis showed no significant correlation between sleeping nasal resistance and snoring index (partial R2 = .44, P = .071). We used each subject as his own control and compared the snoring profile at a time during sleep when nasal resistance was at its highest (0.550 +/ 0.375 Pa/cm3 per second) and lowest (0.146 +/- 0.090 Pa/cm3 per second) levels. Despite the significant (P < .01) differences in nasal resistance, they were not reflected in the number of snores or their sound intensity. It is concluded that nasal obstruction during sleep is not correlated significantly to frequency or intensity of snoring during exclusively nasal breathing. PMID- 8361296 TI - Image-guided intervention for diagnosis and treatment of disorders of the head and neck. PMID- 8361297 TI - Technique of tracheoesophageal puncture using flexible fiberoptic esophagoscopy. PMID- 8361298 TI - Gold weight or spring implants and MRI. PMID- 8361299 TI - Temporoparietal fascial flap in orbital reconstruction. PMID- 8361300 TI - Suboccipital vestibular neurectomy: results and complications. PMID- 8361301 TI - Endoscopic-guided otosurgery in the prevention of residual cholesteatomas. PMID- 8361302 TI - Directory of otolaryngological societies. PMID- 8361303 TI - A comparison of suture versus laser-assisted microvascular anastomosis (LAMA) in the pig buttock flap model. AB - Introduction of microvascular free-tissue transfer to head and neck surgery has completely altered the current approach to extirpation and reconstruction. The increased flexibility now available offers multiple options for reconstruction and has essentially removed the limitations of size and geometry which existed with other types of repair. Despite these advantages, increased surgical time and potential flap failure loom as limiting factors. Since the initial use of sutures to perform microvascular anastomoses, numerous experiments have been conducted in order to identify other options for vessel approximation. Laser-assisted microvascular anastomosis (LAMA) was first attempted with the neodymium-yttrium aluminum garnet (Nd:YAG) laser and, subsequently, other wavelengths were used in experimental models. Success with this technique has been repeatedly documented. Although a comparable animal model to study skin flaps was initially described in 1979, little is currently available in the literature that describes the actual use of a microvascular free flap model. Certainly, nothing exists regarding the role of LAMA and microvascular free-tissue transfer. This study was designed to establish a reliable and reproducible animal model to study free-tissue transfer. Through the use of laser Doppler flowmetry, values of blood perfusion of flaps can be determined. Anastomoses with standard suture and various laser-assisted techniques could then be done and compared, analyzing the parameters of time and blood flow. Histologic evaluation could be correlated with clinical observations. In so doing, LAMA could be objectively evaluated as a potentially viable method of vascular reconstruction in microsurgical free-tissue transfer. PMID- 8361304 TI - The role of H2 antagonists in perennial allergic rhinitis. AB - The biological effects of anti-H2 in allergic reactions are dose dependent: low doses enhance, and high doses significantly decrease the reaction of hypersensitivity. The administration of cimetidine H2 antagonist to 20 perennial allergic rhinitis patients brought about an abatement in the symptoms and a decrease in the total serum immunoglobulin E (IgE) levels in 72% of treated patients, but no variation was perceived in placebo-treated patients. These results strengthen the hypothesis of anti-H2-induced immunoregulatory effects and suggest a possible way of inhibiting IgE synthesis in vivo. PMID- 8361305 TI - Effect of specific bacteria on lymphocyte proliferation in diseased and nondiseased tonsils. AB - Tonsillar tissue lymphocyte (TTL) function as measured by lymphocyte proliferation was assessed in vitro in 38 tonsils--30 diseased and 8 normal controls. TTLs from diseased and control tonsils were challenged with intact, heat-inactivated bacteria which may be found in the core of diseased tonsils; these bacteria were Streptococcus pyogenes and Hemophilus influenzae type B (HIB), as well as the dominant bacterium (DB) grown from that particular tonsillar core. The phytomitogen leukoagglutinin (LA) was used as a nonspecific activator. Lymphocyte proliferation was quantified and reported using a stimulation index (SI) which was based upon viable cell counts at 2, 4, and 6 days following inoculation. Overall, the greatest degree of lymphocyte proliferation in diseased TTLs (SI = .91) was produced by HIB. However, both SP and HIB produced more lymphocyte proliferation in the nondiseased TTLs than in the diseased TTLs (P < .01). H influenzae (non-B) and group A beta-hemolytic streptococci were the pathogens most frequently cultured as the dominant bacteria from the core of diseased tonsils; Streptococcus viridans was most frequently cultured in nondiseased tonsils. The DB caused greater TTL proliferation in diseased (SI = .89) versus control (SI = .63) TTLs (P < .001). These findings suggest a differential proliferative response in vitro for diseased and nondiseased TTLs in response to specific bacteria. The role of possibly pathogenic bacteria and commensals, as well as the implications for clinical disease, are discussed. PMID- 8361306 TI - Immunoperoxidase study of the endolymphatic sac in Meniere's disease. AB - A growing body of evidence suggests that some cases of Meniere's disease may be mediated by immune mechanisms. Because endolymphatic sac dysfunction is believed to be an underlying cause of Meniere's disease, this study used immunohistochemical techniques to demonstrate the presence of immune complex deposition in the sacs of patients with Meniere's disease. Positive immunoglobulin G (IgG) staining was noted in 10 of 23 sac biopsies from Meniere's patients, with 2 specimens showing perivascular deposition. Only 1 of 5 control specimens was only slightly positive for IgG. Clinical correlation showed a statistically significant increase in disease bilaterality (P < .05), larger summating potential/action potential (SP/AP) ratios with electrocochleography (ECoG), and a tendency toward worse hearing and more progressive disease among the immunopositive Meniere's patients. The results provided histological evidence of immune injury in the endolymphatic sacs of patients with Meniere's disease. PMID- 8361307 TI - An analysis-by-synthesis approach to the estimation of vocal cord polyp features. AB - This paper deals with a new noninvasive method of estimating vocal cord polyp features through hoarse-voice analysis. A noteworthy feature of this method is that it enables us not only to discriminate hoarse voices caused by pathological vocal cords with a single golf-ball-like polyp from normal voices, but also to estimate polyp features such as the mass and dimension of polyp through the use of a novel model of pathological vocal cords which has been devised to simulate the subtle movement of the vocal cords. A synthetic hoarse voice produced with a hoarse-voice synthesizer is compared with a natural hoarse voice caused by the vocal cord polyp in terms of a distance measure and the polyp features are estimated by minimizing the distance measure. Some estimates of polyp dimension that have been obtained by applying this procedure to hoarse voices are found to compare favorably with actual polyp dimensions, demonstrating that the procedure is effective for estimating the features of golf-ball-like vocal cord polyps. PMID- 8361308 TI - Facial nerve near the external auditory meatus in man: computer reconstruction study--preliminary report. AB - The anatomy of the facial nerve relative to its intratemporal and extratemporal courses varies over time with developmental changes. Otologic and parotid surgery in infants and children demands detailed knowledge of the precise anatomy of the facial nerve with respect to the tympanic ring and external auditory canal. The authors analyzed this area using our three-dimensional (3-D) computer-aided reconstruction and measurement method studying the spatial relations of the facial nerve to the tympanic ring and stylomastoid foramen. Temporal bones from five normal individuals aged 36 gestational weeks, 3 months, 8 months, 4 years, and 17 years were retrieved from the temporal bone collection stored at the Elizabeth McCullough Knowles Otopathology Laboratory in Pittsburgh. Three dimensional reconstruction of the facial nerve comparing the developmental anatomy across the various age groups provides the surgeon with the technical information necessary to address problems in this area. PMID- 8361309 TI - Ionized serum calcium levels following combined treatment for cancer of the head and neck. AB - Thyroid function may be reduced after treatment of cancer of the head and neck, and hypothyroidism is much more common after combination therapy. Whether hypoparathyroidism and subsequent hypocalcemia also occur after such treatment is unknown. Few related studies have been published in which changes in total serum calcium have been studied after cancer treatment with radioactive iodine or external radiation. Twenty-two disease-free head and neck cancer patients were studied, 1 to 3 years after multimodal treatment, to determine if changes in serum ionized calcium levels or thyroid function were present. Our results suggest that parathyroid function, as represented by ionized calcium levels remains normal after multimodality (surgery, radiation and/or chemotherapy) combined treatment. PMID- 8361310 TI - Ossification patterns of the tympanic facial canal in the human fetus and neonate. AB - Dehiscences in the bony facial canal are comparatively common in the human adult. The highest incidence occurs in the tympanic segment of the facial nerve near the region of the oval window. Thirty-three fetal temporal bones, ranging from 16 to 40 weeks' gestation, and four from 1, 2, 4 and 12 weeks' postpartum neonates, were studied to evaluate the normal patterns of ossification of the fallopian canal of the tympanic facial nerve segment in the human. The tympanic facial nerve segment elongates three-fold during this period (from 1 mm to 3 mm). The ossification starts at 21 weeks' gestation anteriorly from apical otic ossification centers and at 26 weeks from canalicular ossification centers near the stapedius muscle. The ossification proceeds in an anterior-to-posterior direction as two periosteal shelves of bone surround the facial nerve. The superior periosteal bony ledge contributes 75% of the circumference of the fallopian canal. The anterior ossification center forms over 83% of the fallopian canal length. The two centers fuse post partum near the region of the oval window. The anatomic location of the facial nerve, nerve branching, and neural vasculature precede ossification. In 80% of the paired temporal bones, this ossification pattern appears to be symmetrical. The patterns and incidence of bony dehiscences within the tympanic fallopian canal segment can be explained by these observations. This study demonstrates that fallopian canal dehiscences are not congenital anomalies, but variations of normal developmental anatomic processes. PMID- 8361311 TI - Parietal bone graft and titanium plate fixation in nasal reconstruction. PMID- 8361312 TI - Directory of otolaryngological societies. PMID- 8361313 TI - Determination of vocal fold mucosal wave velocity in an in vivo canine model. AB - The vocal fold traveling wave is essential to normal voice production. The present investigation examined whether the velocity of the traveling wave (TWV) could be consistently determined in an in vivo canine model and if traveling wave velocity is affected by changes in the amplitude of recurrent laryngeal nerve stimulation (RLNS) and superior laryngeal nerve stimulation (SLNS). The results showed that traveling wave velocity increased with an increase in recurrent laryngeal nerve stimulation at low constant superior laryngeal nerve stimulation, but was poorly correlated with increases in recurrent laryngeal nerve stimulation at a high level of superior laryngeal nerve stimulation. Furthermore, traveling wave velocity was significantly correlated with superior laryngeal nerve stimulation at constant recurrent laryngeal nerve stimulation. This study demonstrated the feasibility of objectively measuring traveling wave velocity in vivo. PMID- 8361314 TI - Revision stapedectomy. AB - The need for revision stapedectomy surgery still exists despite the many changes that have occurred in the surgical technique for the treatment of stapedial otosclerosis over the past 30 years. Sixty-six revision stapes operations were analyzed to determine the causes of failure of previously operated cases of stapedial otosclerosis, and to evaluate the hearing results following a revision stapedectomy. Failure was most often due to erosion of the incus (41%), displacement of the prosthesis from the incus (24%), or migration of the prosthesis from the center portion of the oval window (24%). Postoperative improvement of hearing was observed in 81% of ears operated on for a conductive hearing loss. Closure to within 10 dB, however, occurred in 61%. Two ears suffered a deterioration in the sensorineural hearing level following the revision surgery. Speech discrimination scores following revision surgery were improved in 5% of ears and unchanged in the remainder. Although the overall hearing results are less favorable than those seen in primary stapedectomy, revision stapedectomy surgery should continue to be offered to patients whose primary stapes surgery failed or whose initial good result declined over time. PMID- 8361315 TI - Factors affecting the development of cerebrospinal fluid leak and meningitis after translabyrinthine acoustic tumor surgery. AB - Meningitis and cerebrospinal fluid (CSF) leak are serious complications of acoustic tumor surgery. Previous reports have varied in the incidence of and the predisposing factors to these complications. This study reviews a series of 723 acoustic tumors removed via the translabyrinthine approach at the House Ear Clinic in Los Angeles. The incidences of CSF leak and meningitis were 6.8% and 2.9%, respectively. The patients who developed these problems were compared to the remainder of the study population for differences in age at surgery, tumor size, operative time, and length of hospital stay. Meningitis occurred more frequently in larger tumors, and patients with either complication had a longer hospital stay. The presence of CSF leak did not predispose to meningitis. It is concluded that technical factors account for postoperative CSF leak and meningitis after translabyrinthine acoustic tumor removal. PMID- 8361316 TI - Intrasubject test-retest variability in clinical electrocochleography. AB - Seventeen healthy volunteers without a history of auditory or vestibular difficulty and with normal screening audiometry had bilateral (34 ears) electrocochleography performed repeatedly at 1-week intervals. Each subject had from four to seven electrocochleograms performed on each ear. Measurements were made in the external auditory canal using a gold-foil "TIPtrode." Amplitude and latency for the summating potential (SP) and action potential (AP) were measured and SP/AP ratios were calculated. Averages and standard deviations for amplitude, latency, and SP/AP ratios were computed. The average SP/AP ratio was 0.22 with a standard deviation of 0.06. The range was 0.04 to 0.50. The average difference between the highest and lowest SP/AP ratio for a given individual was 0.155 (i.e., the range 0.03 to 0.31) with a standard deviation of 0.07. These normative data are useful in assessing the results of dehydration electrocochleography and in establishing how much test-retest variation is required to suggest pathology. PMID- 8361318 TI - Treatment of an acoustic neuroma in an only-hearing ear: case reports and considerations for the future. AB - Current options regarding the treatment of acoustic neuroma in an only-hearing ear include: observation, attempted hearing preservation surgery, and stereotactically guided radiation therapy. A patient who had a left labyrinthectomy for Meniere's disease presented 15 years later with a large right acoustic neuroma. Due to anticipated profound deafness, he fit the criteria for cochlear implantation. Promontory stimulation of the left ear was positive. He underwent successful left cochlear implantation with the Nucleus 22-channel device and was successfully rehabilitated. He then underwent translabyrinthine removal of his right-sided 2.5-cm acoustic neuroma. This case is used to illustrate a new option available to those faced with treating a patient with acoustic neuroma in an only-hearing ear. How this approach may fit in with other available options will be discussed. PMID- 8361317 TI - Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice. AB - Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo. PMID- 8361319 TI - Hemodynamics of the rodent abdominal skin flap following primary ischemia. AB - The effect of varying periods of ischemia and reperfusion times on subsequent blood flow was studied in the rodent abdominal skin flap. Using perfusion fluorometry, measurements of blood flow were quantified in 60 Sprague-Dawley rats undergoing clamp-induced ischemic periods ranging from 0 to 6 hours and reperfusion times ranging from 2 to 8 hours. Flaps subjected to ischemia times of 0, 2, 4, or 6 hours require 8 hours of reperfusion time before reaching baseline levels of blood flow. Blood flow in flaps subjected to 6 hours of ischemia was statistically less than the flow in flaps ischemic for 0, 2, and 4 hours and was directly related to length of reperfusion. These results demonstrate that flap perfusion does not fully take place immediately after clamp release. The factors thought to be responsible for these findings and the implications for the design and interpretation of flap ischemia experiments are discussed. PMID- 8361320 TI - Coronal CT scan abnormalities in children with chronic sinusitis. AB - Coronal computed tomography (CT) scans are currently the optimal study to display the normal and abnormal anatomy in children with chronic and recurrent acute sinusitis after failure of medical therapy. To assess the extent and distribution of disease as well as associated anatomic abnormalities in this pediatric population, 74 coronal CT scans of children with continued symptoms of sinusitis after failure of extensive medical therapy were reviewed retrospectively. Twelve children with cystic fibrosis showed the characteristic features of medial displacement of the lateral nasal wall in the middle meatus and uncinate process demineralization, creating the appearance of a maxillary sinus mucocele. Nine of these 12 children had increased attenuation in the maxillary sinus on soft-tissue windows. In the remaining 62 children, a significantly greater frequency of disease, when compared with that reported for adults, was seen in the maxillary, anterior ethmoid, posterior ethmoid, and frontal sinuses. Children with asthma (n = 33) had more extensive disease. Bony anatomic abnormalities were similar to those reported for adults, except for a lower incidence of septal deformity. PMID- 8361321 TI - Penetrating trauma of the oropharynx in children. AB - Penetrating trauma of the oropharynx is not an uncommon problem in the pediatric population. Innocuous injuries with minor soft-tissue trauma have been associated with severe neurologic sequelae. A review of 77 oral trauma cases that occurred from 1981 to 1990 at Boston Children's Hospital was undertaken to see if constant factors could be identified so that a treatment protocol might be outlined for these patients. Twenty-three (30%) patients sustained injury to the soft palate and peritonsillar area. Fifty percent of these cases required surgical debridement and repair. None of the 23 patients developed neurological sequelae. Physical examination may not correlate with the development of symptoms nor the mechanism of injury. Care should be taken during the examination to identify any neurological problems that may not relate to the degree of injury. Conservative management can be entertained if no abnormal neurologic findings are noted. PMID- 8361322 TI - Insertional trauma of multichannel cochlear implants. AB - Insertional trauma to the cochlea from three different multichannel cochlear implant electrodes was evaluated in a single-blind controlled study in fresh human temporal bones. Sixteen fresh human temporal bones were implanted with one of three types of multichannel electrodes (Symbion/InnerAid, Cochlear/Nucleus, or Storz/UCSF). Seven temporal bones were used as controls where a cochleostomy only was created. The temporal bones were evaluated histologically and cochlear histograms of the trauma were created. Although the three electrode designs caused damage which was unlikely to hinder implant performance, a distinct pattern of trauma was seen with each of the three electrode types. The least traumatic of the three electrode designs in this study was the Nucleus type. The degree of insertional trauma may be relevant to changing indications for insertion of cochlear implants as well as for patients with device failure who require reimplantation. PMID- 8361323 TI - Nicotine-induced analgesia in rats: the role of calcium and the diversity of responders and nonresponders. AB - Following a single dose of nicotine, (NIC, 1 mg/kg s.c.), 60% of tested rats revealed significant antinociception as measured by the tail-flick (TF) test, and were classified as responders, with those in which TF latencies did not change, nonresponders. The following experiments were carried out one week later. In nonresponders, pretreatment with ethylenediaminetetraacetic acid (EDTA, 250 microM/kg s.c. four times every 15 min) followed by 1 mg NIC, produced significant analgesia in 50% of rats, to the same magnitude as did nicotine alone (1 mg) in responders. The other 50% of rats which failed to respond to EDTA pretreatment, all revealed similar analgesia following the higher dose of NIC (1.5 mg/kg s.c.), with similar side effects, as generally observed in responders. In responders, pretreatment with CaCl2 (1.5 mM/kg s.c.) completely abolished NIC (1 mg/kg s.c.)--induced analgesia in all rats. Our data provide stronger evidence and a further verification that EDTA potentiates, whereas CaCl2 completely abolishes, nicotine-induced analgesia in rats; supporting our hypothesis of the involvement of calcium ions in this effect. PMID- 8361324 TI - Lysosomal delivery of ANP receptors following internalization in PC12 cell. AB - Internalization and intracellular processing of ANP-B and C receptors play an important role in regulating cell responsiveness to atrial natriuretic peptides (ANP). Receptor internalization was indirectly monitored with 125I labelled ligand. When 125I-ANP(99-126) was internalized by the cells at 37 degrees C, 55% of the internalized radioactivity was localized in the lysosomal fraction. When receptors were affinity-labelled with 125I-ANP(99-126) and allowed to internalize for varying time periods, two radiolabelled proteins in the m.wt range of 56 and 52 KDa were detected in the cytosolic extract. These proteins appear to be the hydrolytic products of the ANP-C receptor expressed on the plasma membrane. In addition to lysosomal delivery, shedding of the ANP-C receptor from the cell surface was detected following incubation of cells with 125I-ANP(99-126). The dual processes may function to clear exogenous ANP from the extracellular compartments. PMID- 8361325 TI - Endogenous creatinine clearance in the rat: strain variation. AB - The clearance of endogenous creatinine was examined in five strains of rats (Wistar, Wistar Kyoto, Spontaneously Hypertensive Rats, Biobreeding/Worcester diabetic prone and diabetic resistant rats). Creatinine clearance was compared with inulin clearance as the standard. Conditions for clearance measurements were also varied (anesthesia with constant infusion, overnight collection of urine, fed vs. unfed state, single-injection technique). The clearance of creatinine adequately reflects the glomerular filtration rate in three strains (Wistar, Wistar-Kyoto and the Spontaneously Hypertensive Rat). In the two strains of the Biobreeding/Worcester rat creatinine clearance is consistently lower than the inulin clearance. When creatinine clearance is measured from an overnight collection of urine with food withheld it is always lower than when food is present. This clearance should always be validated by comparison with inulin clearance measured simultaneously or under comparable conditions. The ease with which endogenous creatinine clearance can be measured makes it a reasonable method when large numbers of repeated determinations of glomerular filtration rate are required. PMID- 8361326 TI - Absorption of methylmercury from hair ingested by rats. AB - Hair taken from rats dosed with 203Hg-labeled methylmercury was fed to previously untreated rats in order to determine if the organomercurial was available for release from the hair matrix within the gut lumen and for subsequent systemic absorption. Cumulative fecal excretion data were consistent with an absorption of about 80% of the ingested methylmercury. The relative amounts of methylmercury and of its metabolite, inorganic mercury, in the feces indicated that the percentage of the parent compound released from hair within the intestine equaled or exceeded the estimated bioavailability. Radioactivity in tissues of animals killed 42 hr following hair consumption confirmed that mercury absorption had occurred. PMID- 8361327 TI - Inhibitors of Ca2+ channels, calmodulin and protein kinases prevent A23187 and other inductions of metallothionein mRNA in EC3 rat hepatoma cells. AB - The role of calcium in the induction of MT mRNA has been studied in EC3 rat hepatoma cells, using various inducers (A23187, TPA, norepinephrine, and 2 chloroadenosine) and inhibitors (H7:PK-A and PK-C; W7:calmodulin; verapamil:calcium channel blocker; and TMB-8; cytosolic calcium chelator). The inhibitions of inductions observed in this study were consistent with calcium playing an important role in MT mRNA induction by itself and via crosstalk among the PK-A, PK-C, and calmodulin-dependent protein kinase pathways. Calcium has an important role in the complicated second messenger pathways which result in the positive interaction of transcription factors with the promoters of MT genes. PMID- 8361328 TI - Ouabain causes kaliuresis and works synergistically with aldosterone in vivo. AB - The effect of ouabain on urinary Na and K excretion was compared with that of aldosterone by injecting 0.1 or 0.5 mg ouabain or 0.25 micrograms aldosterone. The administration of 0.25 micrograms aldosterone caused sodium-retention without kaliuresis, whereas the administration of 0.5 mg ouabain caused kaliuresis without sodium-retention. These results indicate that ouabain is a kaliuretic agent. The effect of a combination of aldosterone and ouabain was evaluated by injecting 0.25 micrograms aldosterone simultaneously with 0.1 or 0.5 mg ouabain. The combination of aldosterone and ouabain caused both sodium-retention and kaliuresis. These results indicate that ouabain works synergistically with aldosterone to increase mineralocorticoid action by inducing K depletion from the cells in various tissues. PMID- 8361329 TI - Prolactin protection against lethal effects of Salmonella typhimurium. AB - The immunoregulatory role of prolactin (PRL) has been well established. In order to clarify if the hormone is also able to stimulate a protective activity against pathogens-induced infections we have studied the modifications of the infective capacity of Salmonella typhimurium induced in mice by repeated treatments with ovine PRL. A significant dose-dependent reduction in the mortality rate was observed in comparison to controls. This activity is probably related to the observed increases in phagocytosis and intracellular killing of the peritoneal macrophages and chemotaxis of the peritoneal granulocytes induced by the hormonal treatment. On the contrary, the number of leukocytes in blood was not modified by PRL treatment excluding a mobilization of cells from other districts. Our findings confirm the existence of a linkage between the neuroendocrine and immune systems suggesting a possible role for PRL in the regulation of non-specific immune response. PMID- 8361330 TI - Morphine treatment in vitro or in vivo decreases phagocytic functions of murine macrophages. AB - Studies were performed to compare in vitro and in vivo effects of morphine on the phagocytic function of murine peritoneal macrophages. Macrophage monolayers were incubated with Candida albicans for 30 min in the absence of autologous serum. Morphine added in vitro was found to decrease both the phagocytic activity (percent of phagocytic cells) and the phagocytic index (average number of ingested yeasts per cell) in a concentration-dependent manner, with maximal effects of 26% and 41%, respectively, at 10(-6) M. When morphine was administered in vivo via an implanted 75-mg pellet, there was a 22% decrease in phagocytic activity and a 40% decrease in the phagocytic index. Naltrexone completely blocked the effects of morphine both in vitro and in vivo. The results suggest that morphine is capable of interacting directly with opioid receptors on macrophages, resulting in a decrease in phagocytic function. PMID- 8361331 TI - Neuron-specific enolase (NSE) and non-neuronal enolase (NNE) mRNAs are co expressed in neurons of the rat cerebellum: in situ hybridization histochemistry. AB - Using in situ hybridization histochemistry, we analysed the localization of mRNAs for neuron-specific enolase (NSE) and non-neuronal enolase (NNE) in the rat cerebellum at various postnatal developmental stages. Synthetic 45 meric oligonucleotides corresponding to partial sequences of the non-coding region of rat NSE or NNE mRNA were 35S-labeled to approximately the same specific activity and used as hybridization probes. On examination of the adult rat cerebellum, both NSE and NNE signals were detected in all identified and presumed neurons which included Purkinje cells, internal granule cells and presumed stellate/basket cells in the cerebellar cortex and neurons of the dentate nucleus. Examination of the cerebellum during postnatal development also revealed coexistence of NSE and NNE signals in these neurons from early stages. During development, both signals coincidentally increased in Purkinje cells and neurons of the dentate nucleus, while only NSE signals showed a gradual increase in the internal granule cells in which NNE signals remained at the same level from early postnatal to adult stages. The external granule cells showed NNE signals until postnatal day 7 but thereafter the signals became less distinct, especially in cells if the inner zone of the external granule cell layer. Thus, it was shown that NSE and NNE were commonly coexpressed at the mRNA level in various neurons of the cerebellum except for very undifferentiated external granule cells which expressed only NNE mRNA. PMID- 8361332 TI - Molecular cloning of a developmentally regulated brain protein, chicken drebrin A and its expression by alternative splicing of the drebrin gene. AB - Drebrins are developmentally regulated proteins found in the chicken brain and are classified into three forms, E1, E2 and A. Previously we isolated two cDNAs corresponding to the embryonic drebrin mRNAs from a chick embryo cDNA library. They differed in that an internal 129-nucleotide sequence, designated ins1, was inserted in the cDNA encoding drebrin E2 and was deleted in the other cDNA encoding drebrin E1. To search for the cDNA clone encoding drebrin A, a cDNA library of 1-day-old chick brains was screened using embryonic drebrin cDNA fragments as probes. Consequently, a novel cDNA was isolated, the sequence of which was entirely identical with that of drebrin E2 except for the insertion of a 138-nucleotide sequence, designated ins2, in the 5' direction immediately upstream from ins1. Since the translation product of the entire coding region was similar to that of drebrin A, this cDNA should correspond to the mRNA for drebrin A. Sequencing analysis of three drebrin cDNAs clearly indicated that the heterogeneity of chicken drebrins was caused by the insertion or deletion of the two sequences, ins1 and ins2. The amino-terminal half region including ins2 and two short sequences in the carboxyl-terminal region of the predicted drebrin A were highly evolutionarily conserved. Cloning and sequencing of the drebrin gene revealed that ins1 and ins2 were independently encoded by separate exons and three drebrin isoforms were thought to arise by alternative splicing from a single drebrin gene. The difference in the time course of expression and tissue distribution of each drebrin suggests that the machinery of alternative splicing site selection of the drebrin gene is regulated in a developmental stage dependent and tissue-specific manner. PMID- 8361333 TI - Developmental differences of angiotensinogen mRNA in the preoptic area between spontaneously hypertensive and age-matched Wistar-Kyoto rats. AB - In order to know the possible involvement of the central angiotensin system in hypertension, angiotensinogen mRNA (AomRNA) levels of eight discrete brain areas were measured by Northern blot hybridization analysis in the spontaneously hypertensive rats (SHR), compared with those in age-matched normotensive Wistar Kyoto rats (WKY). In 16-week-old SHR (hypertensive stage), AomRNA levels in the preoptic area (POA), but not in the ventromedial hypothalamus, lateral hypothalamus and mammillary body, among the hypothalamic nuclei, were higher (approximate 50%) than in WKY. There were no differences in other brain areas, such as the striatum, septum, amygdala and cerebellum between both the strains. The AomRNA levels in POA were already higher (38%) in 4-week-old SHR (prehypertensive stage) without significance, and the difference was augmented (82%) in 7-week-old SHR (evolving stage). These results suggest that the developmental changes of AomRNA levels at POA may be related in some aspect to hypertension process. PMID- 8361334 TI - Neuron specific expression of a membrane protein, HPC-1: tissue distribution, and cellular and subcellular localization of immunoreactivity and mRNA. AB - The monoclonal antibody HPC-1 recognizes a protein antigen in the hippocampus, and its specific reactivity to the plasma membrane of the amacrine cell somas and the inner plexiform layer in rat retina has been reported. Sequencing the cDNA indicated in our previous study that the HPC-1 antigen was a membrane protein. By means of immunoblotting, an antiserum against the fusion protein of Escherichia coli beta-galactosidase and the HPC-1 antigen detected several proteins of about 35 kDa in the nervous tissues including retina, cerebral cortex, hippocampus, cerebellum and spinal cord, but no signal was obtained in the non-neuronal tissues. Immunofluorescent histochemistry of the various rat tissues revealed that the HPC-1 antigen was confined to the nervous system, including the matrices of the cerebral cortex and hippocampus, the molecular layer, membranes of granular cell somas and glomeruli in the cerebellum and gray matter of spinal cord. However, little staining was seen in the white matter of the central nervous tissues. Thus, the HPC-1 antigen was accumulated in the synapse-rich regions of neuronal cells. In situ hybridization revealed that the HPC-1 mRNA was present in most, if not all, neurons in the central and peripheral nervous systems except for the retina. In the retina, mRNA signals were detected in amacrine and ganglion cells in which HPC-1 immunoreactivity was absent in their soma, suggesting polarized localization of the HPC-1 mRNA on the ganglion cell axon terminal. PMID- 8361335 TI - Estrogenic regulation of proenkephalin mRNA expression in the ventromedial hypothalamus of the adult male rat. AB - Endogenous opioid peptides and their receptors are regulated by gonadal steroid hormones in the rat hypothalamus. Recent evidence suggests that gonadal steroids are capable of regulating the expression of proenkephalin (PE) mRNA in the ventromedial hypothalamus (VMH) of female, but not male rats. Therefore, we examined the effect of gonadectomy with or without four weeks of hormone treatment on PE mRNA expression in adult male Fisher 344 rats using quantitative in situ hybridization histochemistry. Gonadectomy reduced plasma testosterone and dihydrotestosterone (DHT) levels compared to intact rats, while subsequent estradiol (E2) or DHT treatment increased plasma E2 and DHT levels, respectively. Furthermore, gonadectomy reduced PE mRNA expression in the VMH, but not in the striatum nor the olfactory tubercle compared to intact rats, and this reduction was prevented in the presence of E2, but not DHT. The results suggest that the activation of estrogen receptors normally functions to maintain the level of VMH PE mRNA expression, which is sensitive to hormonal regulation in adult male rats. Thus gonadal steroid hormones might regulate those reproductive functions which are modulated by PE-derived opioid peptides in the male rat brain. PMID- 8361336 TI - Antisense oligonucleotide blocks progesterone-induced lordosis behavior in ovariectomized rats. AB - Antisense oligonucleotides were utilized to interfere with the synthesis of progesterone receptor. A specific aODN was shown to decrease significantly the levels of PR in the T47D cell line known to express the PR gene. The molecule described was proved to be effective in hindering the effect of progesterone on target gene expression in T47D cells. The aODN was then utilized in an in vivo study to test its efficacy on the female rat sex behavior. Its injection in the ventromedial hypothalamus significantly inhibited the estrous responsiveness induced by progesterone. This study provides a clear demonstration of the full involvement of PR in the manifestation of lordosis behavior and demonstrates the activity of an aODN as antiprogestative. PMID- 8361337 TI - Altered expression and phosphorylation of amyloid precursor protein in heat shocked neuronal PC12 cells. AB - The pathology of the Alzheimer's disease (AD) brain, including amyloid plaques, neurofibrillary tangles and neuronal degeneration, indicates that neurons affected by AD exist under conditions of stress. In fact, the brains of AD patients undergo many changes classically associated with the heat shock response, which is one form of a stress response. These changes include reduced protein synthesis, disrupted cytoskeleton, increased number of proteins associated with ubiquitin, and the induction of heat shock proteins. To investigate the response of neurons to stress, we examined neuronal PC12 cells incubated at either 37 degrees C (control cells) or 45 degrees C (heat-shocked cells). After a 30 min exposure at 45 degrees C, the heat-shocked cells exhibited several features characteristic of the classical heat shock response including a 45% reduction in total protein synthesis, the induction of heat shock protein 72, and an increased phosphorylation of the protein synthesis initiation factor eIF-2 alpha. We used this cellular model system to study the neuronal response to stress specifically focusing on protein synthesis elongation factor 2 (EF-2) and the Alzheimer's amyloid precursor protein (APP), the precursor form of beta amyloid peptide. Hyperphosphorylation of EF-2 has been observed in the neocortex and hippocampus of AD brain. However, in our system, we find no hyperphosphorylation of EF-2 in response to heat shock. Heat-shocked neuronal PC12 cells exhibited two additional APP-like polypeptides not present in controls. We also found a significant decrease in the phosphorylation state of APP in response to heat shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361338 TI - Reversible phosphorylation of tau to form A68 in heat-shocked neuronal PC12 cells. AB - A68, the primary protein constituent of Alzheimer's disease-associated neurofibrillary tangles, is an abnormally phosphorylated form of the microtubule associated protein tau. We find that A68 is formed in neuronal PC12 cells when the cells are subjected to a heat shock (45 degrees C for 30 min). A68 was identified by immunoprecipitation with two different anti-tau antibodies (tau-2 and Alz50). Upon separation by SDS-polyacrylamide gel electrophoresis, the tau immunoprecipitates from heat-shocked cells exhibited an additional polypeptide of reduced electrophoretic mobility (approximately 68 kDa) when compared to control cells. A68 was formed with heat shock in the presence of cycloheximide, suggesting that its production occurred by post-translational modification of existing polypeptides. The tau/A68 polypeptides were identified as phosphoproteins by incorporation of 32P into the immunoprecipitates. The phosphorylation of tau to form A68 was reversed with recovery of the intact cells from the heat shock. Finally, immunoprecipitation of lysates from heat-shocked cells with antibodies to heat shock protein (hsp) 72/73 resulted in co precipitation of tau with hsp 72, which indicates a stable complex formation between these two proteins. On the other hand, A68 remained unassociated with hsp during the heat shock. These results suggest that tau is reversibly phosphorylated to form A68 in neuronal PC12 cells under conditions of stress. PMID- 8361339 TI - Dopamine antagonist haloperidol increases carboxypeptidase E mRNA in rat neurointermediate pituitary but not in various other rat tissues. AB - Carboxypeptidase E (CPE) is involved with the biosynthesis of many neuropeptides, including several whose genes are regulated by haloperidol treatments. In this study, we examined whether haloperidol alters CPE mRNA levels in a variety of tissues. Rats were treated for either 1, 3, 7, 14, or 21 days with 2 mg/kg haloperidol, and then Northern blot analysis performed on RNA from neurointermediate pituitary, anterior pituitary, hypothalamus, striatum, cerebellum, and adrenal. The 14 and 21 day treatments produced a significant 90 110% elevation of CPE mRNA in neurointermediate pituitary. However, the levels of CPE mRNA in the other tissues were not significantly influenced by the haloperidol treatments. This finding indicates that CPE is not co-regulated with peptide hormone mRNAs in all tissues. PMID- 8361340 TI - Distribution of type II adenylyl cyclase mRNA in the rat brain. AB - We studied the distribution of type II Ca2+/calmodulin (CaM)-insensitive adenylyl cyclase mRNA in the adult rat brain by in situ hybridization histochemistry. Although type II adenylyl cyclase mRNA was distributed throughout the rostrocaudal extent of the brain, the labeling intensity varied among regions. Strong expression was seen in fairly restricted regions such as CA1 and dentate gyrus of the hippocampus, some thalamic nuclei, mammillary nucleus, dorsal raphe nucleus, parabrachial nucleus and locus coeruleus. The distribution of this type of mRNA was significantly different from that of type I Ca2+/CaM-sensitive adenylyl cyclase mRNA. The characteristic localization of type II mRNA suggests that this type of adenylyl cyclase may be involved in some neuronal functions different from the type I enzyme. PMID- 8361341 TI - Soluble derivatives of beta/A4 amyloid protein precursor in human cerebrospinal fluid are both N- and O-glycosylated. AB - The linkage of the glycan chain to the beta/A4 amyloid protein precursor (APP) in cerebrospinal fluid (CSF) was studied by Western blot analysis. The apparent molecular weight of APP in CSF was reduced from 103 to 100 kDa by N-glycanase, and to 96 kDa by O-glycanase treatment, respectively. These data indicate that APP is both N- and O-glycosylated in one molecule. The extent of glycosylation of APP was not altered in the CSF from patients with Alzheimer's disease. PMID- 8361342 TI - Cell-specific expression of preproenkephalin intronic heteronuclear RNA in the rat forebrain. AB - Using in situ hybridization with multiple probes to the rat preproenkephalin gene, we have identified a novel population of cells in the reticular thalamic nucleus and basal forebrain which express RNA derived from the preproenkephalin gene. These cells contain nuclear RNA from downstream of an alternate transcription start site in intron A of the preproenkephalin gene (Kilpatrick et al., Mol. Cell Biol., 10 (1990) 3717-3726), while in the same cells preproenkephalin exon 2 RNA is undetectable. The results suggest that in this population of cells, preproenkephalin gene transcription initiates from the intron A initiation site, and is regulated by an additional mechanism which results in the accumulation of nuclear preproenkephalin intron A-derived heteronuclear RNA. The anatomical distribution of these cells indicates that they may be involved in the control of cerebral cortical function. PMID- 8361343 TI - Hormonal regulation of androgen receptor mRNA in the brain and anterior pituitary gland of the male rat. AB - To determine possible cellular mechanisms governing androgen action in the brain, we examined the hormonal regulation of androgen receptor (AR) mRNA in neural tissues by Northern blot hybridization and RNase protection analysis. While a single hybridizable species of AR mRNA of approximately 11 kb was found in the anterior pituitary gland (AP) and ventral prostate gland (VP), an additional species of AR mRNA, approximately 2 kb smaller, was revealed in neural tissues. Furthermore, in these neural tissues, hormonal regulation of the two species of mRNA was coordinated; long-term castration increased levels of both forms, while testosterone replacement reduced them. The same pattern of regulation was observed for the single 11 kb form in the AP. An RNase protection assay was validated and utilized to quantitatively analyze the hormonal regulation of AR mRNA. Castration (4 days) resulted in significantly increased AR mRNA in the AP and hypothalamic-preoptic area, but not the amygdala, which subsequent administration of dihydrotestosterone (DHT; 1 day; 2 mg/animal) significantly decreased. In the AP, administration of estradiol benzoate (EB) for 1 or 5 days also reversed this effect. However, EB treatment increased the amount of total RNA isolated per gland. Consequently, when the data are normalized to RNA content per gland, 5 days of EB treatment resulted in a significant increase in AR mRNA content. These findings suggest that in contrast to the AP and VP, two forms of androgen receptor mRNA exist in the brain. In addition, there appears to be tissue and hormone specific regulation of AR mRNA. PMID- 8361344 TI - Expression of prostaglandin endoperoxide synthase in rat brain. AB - Developmental and regional expression of prostaglandin endoperoxide synthase (PES) transcript was examined in the rat brain and in primary mixed cultures of neurons and glial cells from neonatal brain. Although the PES mRNA level in the brain was much lower than that in peripheral rat tissues such as lung, liver, spleen and kidney, a significant 3.0 kb band was detected in brain samples by Northern blot analysis. During development, PES mRNA was first detectable at postnatal day 7, and increased thereafter toward adulthood. The highest level of 3.0 kb PES mRNA was observed in the olfactory bulb, midbrain, and hypothalamus; and the lowest level in the hippocampus. In primary cultures of neonatal brain cells, the level of 3:0 kb transcript of PES transiently and dramatically increased about 30-fold on the third day after plating. Simultaneously, two cross hybridizing signals were detected at 4.0 and 7.0 kb. This increase in PES mRNAs was completely inhibited by addition of cytosine-1-beta-D-arabinofuranoside. The induction of PES mRNA was in parallel with the increase in PES protein, as assessed by Western blot analysis. Immunostaining of cultured cells with anti-PES monoclonal antibody revealed that PES protein was induced mainly in neurons but not in glial cells. These results suggest that PES is expressed in the central nervous system at a low concentration under normal conditions, and that the neuronal cells possess an ability to express high levels of PES mRNA and protein. PMID- 8361345 TI - Sodium dodecyl sulfate- and carbamylcholine-induced changes in circular dichroism spectra of acetylcholine receptor synthetic peptides. AB - The effect of sodium dodecyl sulfate (SDS) on the conformation of acetylcholine receptor alpha-subunit synthetic peptides was investigated by circular dichroism. In the presence of SDS (0.01-0.02%), the affinity of a 173-204 32 residue peptide and a 172-227 56 residue peptide for the competitive antagonist alpha bungarotoxin increases about 10-fold to the nanomolar range. Circular dichroism spectroscopy of these peptides revealed significant changes in the secondary structure of the peptides in the presence of SDS at concentrations below the critical micelle concentration. It is concluded that SDS induces a conformation of the peptides that is conductive to high affinity binding. Carbamylcholine, an acetylcholine analog, produced small but significant changes in the spectrum of the 173-204 peptide. This change could be the result of agonist-induced conformational changes in this region of the acetylcholine receptor alpha-subunit or to changes in the asymmetric environments of aromatic chromophores in the binding site. These studies demonstrate that synthetic peptides alone are capable of retaining significant functional activity and contain significant secondary structure. PMID- 8361346 TI - Structure and regulation of the gene encoding the neuron-specific protein PEP-19. AB - PEP-19 is a 61 amino acid polypeptide that is localized to neurons. PEP-19 is translated from a 0.6 kb poly(A)+ RNA; however, the gene from which it is transcribed spans more than 30 kbp and comprises three exons and two large introns. Exon 1 contains the 5'-untranslated region of PEP-19 and the first three amino acids of the coding sequence; exon 2 codes for the next 17 amino acids while the majority of the PEP-19 mRNA, comprising the remaining 42 amino acids and the 3'-untranslated region, is in exon 3. Gel retardation analysis identifies a region of DNA in the putative promoter of PEP-19 that binds preferentially to nuclear extracts from cerebellum. However, constructs containing 1.35 kbp of 5' upstream genomic DNA of PEP-19 fused to lacZ do not express in transgenic mice, suggesting that intragenic DNA may be essential for the regulation of PEP-19. PMID- 8361347 TI - Reserpine causes differential changes in the mRNA levels of chromogranin B, secretogranin II, carboxypeptidase H, alpha-amidating monooxygenase, the vesicular amine transporter and of synaptin/synaptophysin in rat brain. AB - Brains of rats treated with a high dose of reserpine were analyzed by in situ hybridization. The mRNA levels of several components of large dense core and small synaptic vesicles were determined. After drug treatment the secretogranin II message was elevated in the parvocellular neurons of the paraventricular nucleus, in the zona incerta, dorsal raphe, locus coeruleus and in the nucleus tractus solitarius. The levels of chromogranin B mRNA were increased in the dorsal raphe and in the substantia nigra compacta. In control animals messages for synaptin/synaptophysin could be found in most of the nuclei investigated, that of the vesicular amine transporter was only detectable in substantia nigra compacta, the dorsal raphe and the locus coeruleus whereas those of carboxypeptidase H and the alpha-amidating monooxygenase could only be determined in the paraventricular nucleus. All these messages were not changed after reserpine. We conclude that the chromogranin B/secretogranin II messages are regulated concomitantly with various neuropeptides. They represent useful general markers to identify stimulated neurons. Our results are consistent with the concept that stimulation of neurons leads to an increased synthesis of secretory peptides and consequently to large dense core vesicles filled with higher quanta of peptides. PMID- 8361348 TI - Regulation by Ca2+ in the Yersinia low-Ca2+ response. AB - The Yersinia low-Ca2+ response (LCR) is a regulatory response in which a set of plasmid-borne operons is transcriptionally regulated at 37 degrees C in response to the presence or absence of mM concentrations of Ca2+. LCR-regulated operons encode secreted proteins with regulatory and virulence roles as well as non secreted regulatory proteins and components of the secretion machinery. Downregulation by Ca2+ is imposed by a signalling cascade that includes secreted proteins and possibly also components of the secretion system and is hypothesized to act on membrane-bound inductive components. An important role in LCR induction is played by LcrD, an inner-membrane protein with homologues in several virulence associated and flagella assembly-related systems in diverse bacterial species. The mechanism of signal transduction in response to Ca2+ is not known, and the proteins that bind DNA to downregulate transcription have not been identified. PMID- 8361349 TI - Physical organization of lipids in the cell wall of Mycobacterium chelonae. AB - Mycobacterial cell wall functions as an effective permeability barrier, making these bacteria resistant to most antibacterial agents. It has been assumed that this low permeability was due to the presence of a large amount of unusual lipids in the cell wall, but it was not known how these lipids are able to produce such an exceptional barrier. We report here the first experimental evidence on the physical arrangement of these lipids based on X-ray diffraction studies of purified Mycobacterium chelonae cell wall, a result suggesting that the hydrocarbon chains of the cell-wall lipids are arranged predominantly in a direction perpendicular to the cell wall surface, probably producing an asymmetric bilayer structure. PMID- 8361350 TI - Multicopy plasmid instability: the dimer catastrophe hypothesis. AB - Multimer formation reduces plasmid copy number and is an established cause of segregational instability. Nevertheless, it is difficult to rationalize observations that low levels of dimers can cause severe instability, if we assume they are distributed evenly in cell populations. We report here that dimer distribution is in fact heterogeneous in recombination-proficient strains. Most cells in the population contain only monomers; dimers are confined to a small subpopulation from which plasmid-free daughters arise at high frequency. In a rec+ culture where 4% of pBR322 molecules are dimers, more than half are in dimer only cells. We show that this situation is inevitable because dimers replicate at twice the rate of monomers. Runaway multimerization is avoided because dimer containing cells grow more slowly than their monomer-containing counterparts. A computer simulation is used to show how dimers proliferate after formation by homologous recombination. The equilibrium concentration of dimers is proportional to the inter-plasmid recombination rate and is essentially independent of the rate at which homologous recombination converts dimers to monomers. PMID- 8361351 TI - The alkane oxidation system of Pseudomonas oleovorans: induction of the alk genes in Escherichia coli W3110 (pGEc47) affects membrane biogenesis and results in overexpression of alkane hydroxylase in a distinct cytoplasmic membrane subfraction. AB - The alkane hydroxylase system of Pseudomonas oleovorans, which catalyses the initial oxidation of aliphatic substrates, is encoded by three genes. One of the gene products, the alkane hydroxylase AlkB, is an integral cytoplasmic membrane protein. Induction leads to the synthesis of 1.5-2% AlkB relative to the total cell protein, both in P. oleovorans and in recombinant Escherichia coli DH1. We present a study on the induction and localization of the alkane hydroxylase in E. coli W3110, which appears to be an interesting host strain because it permits expression levels of AlkB of up to 10-15% of the total cell protein. This expression level had negative effects on cell growth. The phospholipid content of such cells was about threefold higher than that of wild-type W3110. Freeze fracture electron microscopy showed that induction of the alk genes led to the appearance of membrane vesicles in the cytoplasm; these occurred much more frequently in cells expressing alkB than in the negative control, which contained all of the alk genes except for alkB. Isolation and separation of the membranes of cells expressing alkB by density gradient centrifugation showed the customary cytoplasmic and outer membranes, as well as a low-density membrane fraction. This additional fraction was highly enriched in AlkB, as shown both by SDS-PAGE and enzyme activity measurements. A typical cytoplasmic membrane protein, NADH oxidase, was absent from the low-density membrane fraction. alkB expression in W3110 changed the composition of the phospholipid headgroup in the membrane, as well as the fatty acid composition of the membrane. The major changes occurred in the unsaturated fatty acids: C16:1 and C18:1 increased at the expense of C17:0cyc and C19:0cyc. PMID- 8361352 TI - Molecular genetic analysis of the moa operon of Escherichia coli K-12 required for molybdenum cofactor biosynthesis. AB - A 3.2 kb chromosomal DNA fragment which complements the defects in a series of twelve moa::Mucts insertion mutants has been sequenced. Five open reading frames (ORFs) were identified and these are arranged in a manner consistent with their forming an operon. The encoded proteins (MoaA-MoaE) have predicted molecular weights of 37,346, 18,665, 17,234, 8843 and 16,981 respectively. Examination of subclones of the whole locus in an expression system demonstrated the predicted products. N-terminal amino acid sequences for the moaA, B, C and E products confirmed the translational starts. Genetic analysis distinguished four classes of moa mutants corresponding to genes moaA, C, D and E. Potential promoter sequences upstream of moaA and a possible transcription termination signal have been identified. Genetic analysis of the chlA1 and chlM mutants, which have been biochemically characterized as defective in molybdopterin biosynthesis, indicates that these carry lesions in moaA and moaD respectively. The moa locus is orientated clockwise at 17.7 minutes in the chromosome. PMID- 8361353 TI - The presence of a novel type of surface polysaccharide in Rhizobium meliloti requires a new fatty acid synthase-like gene cluster involved in symbiotic nodule development. AB - Bacterial exopolysaccharide (EPS) and lipopolysaccharide (LPS) molecules have been shown to play important roles in plant-bacterium interactions. Here we have demonstrated that the fix-23 loci, which compensate for exo mutations during symbiotic nodule development, are involved in the production of a novel polysaccharide that is rich in 3-deoxy-D-manno-2-octulosonic acid (Kdo) but is not the classical LPS. This molecule is likely to be a surface antigen since antiserum to whole Rhizobium meliloti cells reacts strongly with it, and since mutations in fix-23 result in an inability to produce this polysaccharide and to bind bacteriophage 16-3. It is likely that this Kdo-rich polysaccharide is analogous to certain Escherichia coli K-antigens which are anchored to the membrane via a phospholipid moiety. DNA sequence analysis of one gene cluster of this region revealed that the predicted protein products of six genes exhibit a high degree of homology and similar organization to those of the rat fatty acid synthase multifunctional enzyme domains. PMID- 8361355 TI - The obligate intracellular bacterium Chlamydia trachomatis is auxotrophic for three of the four ribonucleoside triphosphates. AB - Using well-characterized mutant host cell lines, deficient in specific enzymes of energy and nucleotide metabolism, we addressed numerous questions regarding nucleotide metabolism in the obligate intracellular bacterium Chlamydia trachomatis. The results presented indicate that C. trachomatis: (i) does not absolutely depend on mitochondrial generated ATP for survival; (ii) does have a significant draw on host-cell NTP pools but does not have a detrimental effect on the ability of the host cell to maintain its energy charge; (iii) lacks the ability to synthesize purine and pyrimidine nucleotides de novo; (iv) is not capable of interconverting purine nucleotides; and (v) possesses the pyrimidine metabolic-pathway enzymes CTP synthetase and deoxycytidine nucleotide deaminase. In total our results indicate that C. trachomatis is auxotrophic for host-cell ATP, GTP and UTP. In contrast, CTP can be obtained from the host cell or it can be synthesized from UTP by the parasite. PMID- 8361354 TI - Expression of the ferric enterobactin receptor (PfeA) of Pseudomonas aeruginosa: involvement of a two-component regulatory system. AB - Expression of the ferric enterobactin receptor in Pseudomonas aeruginosa is inducible by enterobactin and requires sequences upstream of the structural gene (pfeA). Nucleotide sequencing of a 2.5 kilobase pair (kb) region of DNA immediately upstream of pfeA revealed two open reading frames (ORFs), pfeR and pfeS, which appeared to comprise an operon. The predicted products of pfeR and pfeS (molecular weight 26,796 and 50,597, respectively) exhibited a high degree of homology to response-regulator and sensor components, respectively, of the superfamily of prokaryotic environmentally responsive protein pairs. Consistent with an apparent role in regulating expression of pfeA in response to enterobactin, introduction of pfeR/pfeS into P. aeruginosa on a high-copy-number vector enhanced enterobactin-dependent expression of pfeA. Furthermore, a pfeR mutant obtained by in vitro mutagenesis and gene replacement failed to express PfeA despite the presence of enterobactin in the culture medium. Analysis of the hydropathy profiles of PfeR and PfeS supported a cytoplasmic location for PfeR and a cytoplasmic membrane location for PfeS. PMID- 8361357 TI - Preparation and analysis of isogenic mutants in the transferrin receptor protein genes, tbpA and tbpB, from Neisseria meningitidis. AB - Isogenic mutants were constructed in the tbpA and tbpB genes from Neisseria meningitidis strain B16B6, which code for the transferrin receptor proteins, Tbp1 and Tbp2. Insertion mutants of the tbpA and tbpB genes were obtained by shuttle mutagenesis and by in vitro cassette mutagenesis, respectively. The isogenic mutants were verified by Southern blot and Western blot analysis. Isogenic mutants deficient in Tbp1 or Tbp2 demonstrated a reduced transferrin binding activity in intact cells and total membranes but were incapable of utilizing transferrin iron for growth. Tbp1 could be isolated by affinity methods from the mutant lacking Tbp2 but isolation of Tbp2 from the mutant lacking Tbp1 required the presence of exogenous Tbp1. PMID- 8361356 TI - Isolation and analysis of a linear plasmid-located gene of Borrelia burgdorferi B29 encoding a 27 kDa surface lipoprotein (P27) and its overexpression in Escherichia coli. AB - Using an antiserum of a patient with cutaneous manifestations of Lyme borreliosis we have isolated the gene encoding a 27 kDa protein antigen (P27) of Borrelia burgdorferi B29 from a lambda-gt11 expression library. Nucleotide sequence analysis revealed that it is a basic protein of 248 amino acids with a typical prokaryotic leader sequence of 17 amino acid residues at the N-terminus of the proposed translation product. Biochemical investigations showed that P27 is a surface-exposed lipoprotein. From pulsed-field gel electrophoresis and subsequent Southern blot analysis it is evident that the p27 gene is located on a linear plasmid of a size of approximately 55 kb. It was overexpressed in Escherichia coli and the purified recombinant protein was used for biochemical and serological studies. Northern and Western blot analysis demonstrated that p27 is expressed in the European B. burgdorferi strain B29, but not in the American strain B31. PMID- 8361358 TI - The region of human transferrin involved in binding to bacterial transferrin receptors is localized in the C-lobe. AB - Iron-saturated human transferrin was digested with either chymotrypsin or trypsin to produce C-lobe and N-lobe protein fragments. Individual protein fragments were purified by a combination of gel filtration and Concanavalin A affinity chromatographic procedures. The C-lobe and N-lobe fragments of human transferrin were then used in binding assays to assess their ability in binding to the bacterial transferrin receptors. Competitive binding assays demonstrated that the C-lobe fragment of human transferrin binds as well as intact human transferrin to bacterial transferrin receptors from Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae. Using isogenic mutants of N. meningitidis deficient in either of the transferrin-binding proteins (Tbps), we demonstrated that both transferrin-binding proteins were able to bind to the C-lobe fragment of human transferrin. PMID- 8361359 TI - Identification of an operon involved in the assimilatory nitrate-reducing system of Azotobacter vinelandii. AB - A number of mutants lacking nitrate reductase (Nas-) or nitrite reductase (Nis-) activities have been isolated and characterized. An operon including two new genes (nasA and nasB) has been defined and cloned from an Azotobacter vinelandii gene bank. nasA encodes for nitrite reductase apoenzyme, whereas nasB is specific for nitrate reductase activity. Nitrate reductase exerts a regulatory effect on nasAB. PMID- 8361360 TI - Lactococcus lactis: high-level expression of tetanus toxin fragment C and protection against lethal challenge. AB - To determine if the food-grade bacterium Lactococcus lactis holds promise as a vaccine antigen delivery vector we have investigated whether this bacterium can be made to produce high levels of a heterologous protein antigen. A regulated expression system has been developed which may be generally suitable for the expression of foreign antigens (and other proteins) in L. lactis. The system utilizes the fast-acting T7 RNA polymerase to transcribe target genes, and provides the first example of the successful use of this polymerase in a Gram positive bacterium. When the performance of the expression system was characterized using tetanus toxin fragment C (TTFC) up to 22% of soluble cell protein was routinely obtained as TTFC. Mice immunized subcutaneously with L. lactis expressing TTFC were protected from lethal challenge with tetanus toxin. These results show for the first time that L. lactis is able to express substantial quantities of a heterologous protein antigen and that this organism can present this antigen to the immune system in an immunogenic form. PMID- 8361361 TI - ATPase activity and ATP/ADP-induced conformational change in the soluble domain of the bacterial protein translocator HlyB. AB - The haemolysin exporter HlyB and its homologues are central to the unconventional signal-peptide-independent secretion of toxins, proteases and nodulation proteins by bacteria. HlyB is a member of the ATP-binding cassette (ABC) or traffic ATPase superfamily, and resembles closely in structure and function mammalian exporters such as the multidrug-resistance P-glycoprotein, combining both integral membrane and cytosolic domains. Overproduction of the HlyB cytoplasmic domain as a C terminal peptide fused to glutathione S-transferase allowed the direct affinity purification and concentration of 30-50 mg ml-1 of soluble protein (GST-Bctp) in an apparently dimeric form possessing both transferase and ATPase activity. GST Bctp bound to ADP-agarose and was eluted specifically by ATP and ADP, affinity behaviour which was confirmed in both the full-length HlyB and the unfused HlyB cytoplasmic domain synthesized in vitro. The stoichiometry of binding to MgATP and MgADP was close to equimolar and both ligands induced substantial conformational change in the protein. Mg(2+)-dependent ATPase activity of GST Bctp (Vmax 1 mumol min-1 mg-1, Km 0.2 mM) was comparable with the activity of the bacterial importer MalK and human P-glycoprotein reconstituted into proteoliposomes, and over an order of magnitude higher than in vitro measurements of disaggregated MalK purified from inclusion bodies. Activity was unaffected by inhibitors of F- and V-type ATPases, non-hydrolysable ATP analogues, or translocation substrate, but was severely inhibited by inhibitors of E1E2 (P type) ATPases, and the acidic phospholipid phosphatidyl glycerol. PMID- 8361362 TI - Yeast DNA recombination and repair proteins Rad1 and Rad10 constitute a complex in vivo mediated by localized hydrophobic domains. AB - The Saccharomyces cerevisiae Rad1 and Rad10 proteins are required for damage specific incision during nucleotide excision repair and also for certain mitotic recombination events between repeated sequences. Previously we have demonstrated that Rad1 and Rad10 form a specific complex in vitro. Using the 'two-hybrid' genetic assay system we now report that Rad1 and Rad10 proteins are subunits of a specific complex in the cell nucleus. The Rad10-binding domain of Rad1 protein maps to a localized region between amino acids 809-997. The Rad1-binding domain of Rad10 protein maps between amino acids 90-210. These domains are evolutionarily conserved and are hydrophobic in character. Although significant homology exists between Rad10 and the human-DNA-repair protein Ercc1 in this region, we were unable to detect any interaction between Ercc1 and Rad1 proteins. We conclude that Rad1 and Rad10 operate in DNA repair and mitotic recombination as a constitutive complex. PMID- 8361363 TI - Medicare and Medicaid anti-kickback law. PMID- 8361364 TI - Investing in the 1990s: in search of guidance. PMID- 8361365 TI - Dignity and the child's dental appointment. PMID- 8361366 TI - Is disability income part of your financial plan? PMID- 8361367 TI - Florida dentists still dealing with aftermath of Hurricane Andrew. PMID- 8361368 TI - Visualization of exocytosis by quick freezing and freeze-fracture. PMID- 8361369 TI - Vaccinia virus vectors for study of membrane fusion mediated by human immunodeficiency virus envelope glycoprotein and CD4. PMID- 8361370 TI - Electropermeabilized platelets: a preparation to study exocytosis. PMID- 8361371 TI - Exocytotic membrane fusion as studied in toxin-permeabilized cells. PMID- 8361372 TI - Calculation and control of free divalent cations in solutions used for membrane fusion studies. PMID- 8361374 TI - Use of Tetrahymena and Paramecium in studies of exocytosis. PMID- 8361373 TI - Manipulation of cytosolic free calcium transients during exocytosis in intact human neutrophils. PMID- 8361375 TI - Calcium-dependent membrane-binding proteins in cell-free models for exocytotic membrane fusion. PMID- 8361376 TI - In vitro studies of endocytic vesicle fusion. PMID- 8361377 TI - Fluorescence methods for monitoring phagosome-lysosome fusion in human macrophages. PMID- 8361378 TI - In situ resonance energy transfer microscopy: monitoring membrane fusion in living cells. PMID- 8361379 TI - Detection of sperm-egg fusion. PMID- 8361380 TI - Membrane area and electrical capacitance. PMID- 8361381 TI - Fusion of human immunodeficiency virus-infected cells with uninfected cells. AB - CD4-dependent HIV envelope glycoprotein-induced membrane fusion events play a key role in the life cycle of HIV and are involved both in infection mediated by viral particles and in virally mediated cytopathic processes. The relevant events involve binding interactions between the HIV envelope glycoprotein gp120 and the cellular receptor CD4 and membrane fusion processes mediated by the HIV envelope glycoprotein gp41. A straight forward, rapid, and convenient assay procedure useful for analysis of these processes and identification of inhibitors is described. PMID- 8361382 TI - Intracellular delivery of nucleic acids and transcription factors by cationic liposomes. PMID- 8361383 TI - Electroinjection. PMID- 8361384 TI - pH-sensitive liposomes for delivery of macromolecules into cytoplasm of cultured cells. PMID- 8361385 TI - Kinetics of cell fusion mediated by viral spike glycoproteins. PMID- 8361386 TI - Protein conformational changes in virus-cell fusion. PMID- 8361387 TI - Monitoring protein conformational changes during membrane fusion. PMID- 8361388 TI - Synthetic peptides as probes of function of viral envelope proteins. PMID- 8361389 TI - Simultaneous electrical and optical measurements of individual membrane fusion events during exocytosis. PMID- 8361390 TI - Duramycin increases intracellular calcium in airway epithelium. AB - Duramycin increases short-circuit current (Isc) and net Cl- secretion in tracheal epithelium. We measured the intracellular free calcium ([Ca2+]i) response to duramycin using Indo-1 and bovine and canine tracheal cell suspensions, and the effect of an intracellular calcium chelator, BAPTA, and the protein kinase C inhibitor, staurosporine, on the Isc and [Ca2+]i response to duramycin. [Ca2+]i increased in a dose-dependent manner from basal levels of 34 +/- 5 to 949 +/- 136 nM at 5 x 10(-6) M duramycin. Both BAPTA (50 microM) and staurosporine (5-50 nM) pretreatment blunted the increase in Isc and net Cl- secretion produced by duramycin. BAPTA also blunted the rise in [Ca2+]i produced by duramycin (5 x 10( 6) M) in the presence of extracellular calcium (499 +/- 122 nM). In the absence of extracellular calcium, the duramycin-induced (5 x 10(-6) M) rise in [Ca2+]i was blunted from 949 +/- 136 nM (stimulation in the presence of Ca2+) to 621 +/- 122 nM, and was further decreased in the presence of BAPTA to 197 +/- 42 nM. In contrast, staurosporine (50 nM) pretreatment had no effect on the rise in [Ca2+]i produced by duramycin (basal 90 +/- 27 to 861 +/- 110 nM at 5 x 10(-6) M). Duramycin had no effect on [Ca2+]i in human neutrophils. These data demonstrate that duramycin releases calcium from intracellular stores and stimulates the influx of calcium in airway epithelial cells. These data also demonstrate that, in the presence of protein kinase C pathway blockade, an increase in intracellular free calcium is not sufficient for chloride secretion; thus, duramycin-stimulated chloride secretion may depend upon protein kinase C. PMID- 8361391 TI - In vitro susceptibility of Haemophilus ducreyi to several antibiotics. AB - Haemophilus ducreyi was isolated from 59 (52%) of 113 men with a clinical diagnosis of chancroid. The following MIC50 (MIC90) values for H. ducreyi were obtained: erythromycin 0.14 (0.5) micrograms/ml, trimethoprim 0.25 (8.0) micrograms/ml, ceftriaxone 0.009 (0.14) micrograms/ml, and ciprofloxacin 0.007 (0.04) micrograms/ml. These data indicate that all isolates appear to be fully susceptible to erythromycin and the other antimicrobial agents tested, although ciprofloxacin was the most effective antibiotic. PMID- 8361392 TI - Effects of chlorhexidine diacetate and cetylpyridinium chloride on whole cells and protoplasts of Saccharomyces cerevisiae. AB - Chlorhexidine diacetate (CHA) and the quaternary ammonium compound, cetylpyridinium chloride (CPC), were fungicidal to Saccharomyces cerevisiae A364A and CHA to its mannoprotein mutant LB6-5D. Both CHA and CPC induced leakage of K+ and pentose material from both strains and both agents induced protoplast lysis as well as interacting with crude cell sap. Differences were observed between CHA and CPC in protoplast lysis and in cell sap interaction. Q25 values for A364A with CHA as test agent were 5.6 and 1.6 (fungicidal activity, depending on method of calculation), 1.46 (cell sap interaction) and 0.77 (leakage of pentoses). A sub-lytic concentration of CHA reduced considerably protoplast regeneration. Although the plasma membrane is an important target site for both agents, interaction with other cellular components also contributes to fungal death. PMID- 8361393 TI - Conditions suitable for the recovery of biocide-treated spores of Bacillus subtilis. AB - Various factors were studied in order to determine the optimum conditions for the recovery of Bacillus subtilis spores treated with two iodine preparations, two chlorine-releasing agents or glutaraldehyde. The composition of the recovery medium was not usually important except that counts on brain heart infusion agar were significantly lower than on other media for iodine-treated spores. The addition to recovery media of soluble starch, charcoal, D-glucose or yeast extract usually had no discernible beneficial effect on colony counts. Maximum counts of survivors were obtained after an incubation period of 3 days and an optimum incubation temperature of 30 or 37 degrees C. Germination and outgrowth of biocide-exposed spores were more sensitive to changes in incubation temperature than were control spores. PMID- 8361394 TI - Salmonella and Shigella carriage by gulls (Larus sp.) on the east Black Sea region of Turkey. AB - Sea gull faeces (616 samples in toto) were examined for enteric human pathogens, and 1.3% and 0.60% were found to contain Salmonella spp. and Shigella spp., respectively. All positive samples were near sewage outfalls and refuse tips. The Salmonella serotype was isolated as S. typhi and the Shigella serotype as S. sonnei. Pathogenic bacteria were isolated from the faecal samples collected only in the Trabzon area. PMID- 8361395 TI - On-line measurement of microvascular diameter and red blood cell velocity by a line-scan CCD image sensor. AB - A line-scan charge-coupled device (CCD) image sensor (256 photo sites) was equipped for on-line measurement and calculation of red blood cell velocity and microvascular diameter. The principle of measurement is based on a sequential readout of the CCD-sensor photo signal at predefined time intervals. The velocity is calculated by a computer by cross correlation of a given set of readouts. Rotation of the sensor into a position perpendicular to the microvessel axis allows measurement of the diameter, which is related to the red blood cell column moving under the sensor. At low magnification (up to 38-fold) diameters up to 80 microns can be measured. Calibration, which was performed by comparing diameters measured in vivo by the CCD-based system with microphotographically obtained measurements, revealed a mean CCD/photo ratio of 0.98 +/- 0.08. Calibration of velocity measurements in glass tubes of different diameters by a calibrated pump with known bulk flow resulted in a mean conversion factor of 1.59 +/- 0.2 (mean +/- SD). The CCD sensor is mounted such that it can freely rotate on the microscope. In conjunction with a programmable scanning table, several vessels can be measured sequentially in one preparation. The interval between two combined measurements and calculations of velocity and diameter is 1.1 sec. PMID- 8361396 TI - Differential reactivity of cortical and juxtamedullary glomeruli to adenosine-1 and adenosine-2 receptor stimulation and angiotensin-converting enzyme inhibition. AB - A recently developed modification of the technique of the split hydronephrotic rat kidney enables intravital assessment of vascular reactivity of cortical and juxtamedullary (JM) glomeruli and their vascular network. Effects of the adenosine-1 receptor agonist N6-cyclohexyladenosine (CHA) and the adenosine-2 receptor agonist N-ethylcarboxamide-adenosine (CHA) and the adenosine-2 receptor agonist N-ethylcarboxamide-adenosine (NECA) on these renovascular structures were examined before and after angiotensin II-converting enzyme (CE) inhibition by quinapril (0.9 mg kg-1 iv). CE inhibition was undertaken to test for an interdependence of adenosine and angiotensin II, as we have previously demonstrated for cortical glomeruli and CHA. In the first series of experiments (n = 7), CHA (in local dosages from 10(-8) to 10(-6) mole liter-1 produced a dose dependent vasoconstriction of all preglomerular vessels and a decrease of cortical glomerular blood flow that was markedly attenuated by CE inhibition. In JM glomeruli, CHA also led to a dose-dependent vasoconstriction, but these effects were, on the contrary, unchanged or even increased by CE inhibition. In the second series (n = 6), NECA (in local dosages from 10(-8) to 10(-5) mole liter-1) led to a vasodilation and an increase in glomerular blood flow both before and after CE inhibition in both cortical and JM glomeruli. The reactions induced by NECA alone in the principal preglomerular vessel segments were significantly larger than those under NECA and simultaneous CE inhibition, thereby demonstrating an attenuation of NECA effects induced by CE inhibition. In additional series, we demonstrated a dose-dependent vasoconstriction of all pre- and postglomerular cortical vessel segments by local application of angiotensin I (dosage 10(-8) to 10(-6) mole liter-1) and the abolition of these effects by quinapril. Our findings demonstrate a differential reactivity of cortical and juxtamedullary glomeruli to adenosine receptor agonists and, additionally, an interdependence of adenosine-and angiotensin II-induced renovascular effects. PMID- 8361397 TI - O2 gradients and countercurrent exchange in the cat vitreous humor near retinal arterioles and venules. AB - Recessed cathode O2 microelectrodes were used to measure spatially detailed oxygen tension (PO2) gradients in the vitreous humor near the cat retina. Measurement sites (n = 41 in 8 cats) included single arterioles and venules and parallel vessel pairs. Mean vitreous PO2 was 37.9 +/- 1.5 (SE) Torr. Close to the retinal surface (approximately 200 microns), PO2 was found to be both higher and lower than the vitreous PO2, depending on the proximity of the microelectrode tip to retinal vessels. Both positive (inward) and negative (outward) O2 fluxes (JO2) were measured, consistent with the anatomy and expected boundary conditions in the eye. The PO2 at the closest approach above arterioles was 55.2 +/- 2.3 Torr, significantly higher than in the vitreous (P < 0.0001). All arterioles had outward JO2 with an overall mean of -2.58.10(-6) ml O2/sec/cm2. Some of the venules were also losing O2, but at much lower rates than arterioles. Several venules were gaining O2. Countercurrent transport (A-V shunting) was also seen between vessel pairs. Our experimental results allow theoretical predictions to be made for the axial drop in blood PO2 along an arteriole as a function of blood flow. PMID- 8361398 TI - A micropipette which allows in situ perfusion of arterioles and capillaries. AB - In order to investigate capillary physiology, a glass micropipette system was developed that allowed in situ perfusion of microvessels as well as rapid changes of perfusion solutions. Theta tube (WPI, Inc.; 1.5-mm o.d. glass stock capillary tubing which is divided into two hemicylindrical sides by a central glass septum) was pulled to a smaller diameter of approx 300-600 microns and inserted into the shank of a sharpened cannulating micropipette tip constructed from large-bore glass stock (1.6 mm i.d.). The resulting dead volume between the end of the Theta supply tube and the tip of the outer cannulating tip was approximately 90 nl. The perfusate was driven in a circuit from a pressurized feed reservoir down one side of the Theta supply tube pipette and back through the second side into a reservoir maintained at a lower pressure. The pressure gradient between the two reservoirs established a high-volume flow rate and subsequently a short perfusate transit time from the feed to the collection reservoir. The average pressure in the two reservoirs determined the pressure which drove the perfusate from the cannulating tip. At normal pressures and flows, the time required to change perfusion fluid composition at the pipette tip was less than 1 min, and discharge hematocrit of a red blood cell suspension was indistinguishable from the hematocrit measured in the feed reservoir.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361399 TI - Direct measurement of retinal microvascular pressures in the live, anesthetized cat. AB - Microvascular pressures in retinal circulation were measured in living, anesthetized cat by the servonull micropuncture technique. Of the total vascular pressure drop 32% was in the segment proximal to the large retinal arteries when intraocular pressure was set at 10 mm Hg and decreased to 27% when intraocular pressure was increased to 20 mm Hg. The pressure in the retinal veins was substantially (> 7 mm Hg) greater than intraocular pressure at both values of intraocular pressure. There was negligible pressure drop within venous segment; however, the pressure drop from the retinal veins to the systemic veins was large and cannot be explained on the basis of a venous waterfall within the retina. PMID- 8361400 TI - Effects of nonsteroidal anti-inflammatory drugs on microvascular dynamics. AB - Techniques of intravital microscopy were used to assess the effect of the nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and ibuprofen, on the microcirculation. Hemodynamics in venules of the rat mesentery were studied in terms of vessel diameter, red blood cell velocity, and leukocyte-endothelium interactions: leukocyte-endothelium adhesion (LEA), white blood cell (WBC) marginating flux, and WBC velocity. Measurements were made during (1) control conditions (topical suffusion with ringer-gelatin drip), (2) topically suffused indomethacin or ibuprofen, (3) an induced inflammatory response (suffusion with the chemoattractant N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP)), and (4) concomitant suffusion with FMLP and NSAID. Short term topical suffusion (90 sec) with indomethacin and ibuprofen had little or no effect on control hemodynamics. Five-minute suffusions with indomethacin (5 x 10(-5) to 5 x 10(-4) M) significantly increased LEA while ibuprofen (5 x 10(-3) M) significantly decreased LEA. Topical suffusion with the chemotactic agent FMLP induced inflammation and significantly increased LEA in venules. Treatment with indomethacin during induced inflammation had no effect on the inflammatory reaction in terms of the microvascular hemodynamics measured in this study. Treatment with ibuprofen during induced inflammation significantly reduced LEA and increased red blood cell velocity. In conclusion, although both of the NSAIDs studied here are known to block the cyclooxygenase pathway of arachidonic acid metabolism, the actions of indomethacin and ibuprofen on the inflammatory process are very different with an important effect of ibuprofen being to decrease LEA. PMID- 8361401 TI - Three-dimensional analysis of contrast-filled microvessel diameters. AB - Organ blood flow is controlled, in part, by changes in diameter of resistance vessels. In thick tissue, vessels can be imaged with a microscope using contrast enhancing methods (e.g., fluorescence) and image analysis techniques can be used for quantitative diameter estimations. However, a change in the position of a vessel with respect to the plane of focus can be misinterpreted as a diameter change. In order to address this problem, a 3D image in a light microscope is obtained by serial optical sectioning, and a 3D deconvolution procedure (Avinash et al., 1991, "Fourteenth Association for Research in Otolaryngology Midwinter Meeting, St. Petersberg, FL," Abstract 156) is used to deblur 3D image data. Deblurred sections are computationally projected onto a 2D plane to give an extended-focus image, from which diameter estimates of microvessels are made using a quantitative, 2D diameter-tracking algorithm (Miles, 1987, "Semiautomatic Quantitative Image Analysis of Dynamic in Vivo Cochlear Microvessel Diameters." Ph.D. dissertation, Univ. Michigan; Miles and Nuttall, 1992, IEEE Trans. Biomed. Eng.). Justification for 3D preprocessing before diameter analysis is provided by absolute and relative error analyses using computer-generated synthetic vessels. The 3D diameter analysis technique is validated using a capillary tube of known diameter, filled with fluorescent solution. Demonstration of its applicability is shown in diameter measurements from the vessels of guinea pig cochlea. Our approach, using extended-focus images, minimizes overestimation of microvascular diameters and underestimation of relative diameter changes. Therefore, unambiguous diameter measurements are possible with extended-focus images. PMID- 8361402 TI - Evaluation of carbocyanine-labeled erythrocytes for microvascular measurements. AB - Red blood cells labeled with the carbocyanine dyes, 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate (DiI) and 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), were evaluated for use in making microvascular measurements in rat small intestine and spinotrapezius muscle. We determined the minimum concentration of each dye which produced near maximal fluorescent intensity and labeled cell fraction. These dyes, which have excitation and emission spectra similar to fluorescein and rhodamine derivatives, have a number of advantages over the isothiocyanates: (1) the labeling procedure is quicker, easier, and less expensive; (2) the labeled cell fraction and the fluorescent intensity of DiI and DiO cells are stable for long periods of time in the rat circulation; and (3) DiI labeled cells are brighter and transmit light through overlying erythrocytes better than rhodamine X isothiocyanate. However, in vitro and in vivo evaluations illustrate the potential limiting effects of vessel diameter and cell velocity on the accuracy of microvascular measurements made using this technique. In the small intestine and spinotrapezius muscle preparations, measurements of labeled cell flux were readily reproducible and could be partly automated with image analysis only in capillaries and small venules. Counting labeled cells in larger vessels by human observation or with automation was not reproducible, presumably due to absorption and dispersion of the fluorescent signal by overlying erythrocytes and smearing of the cell image at high cell velocities. PMID- 8361403 TI - Gender differences in facial skin blood perfusion during basal and heated conditions determined by laser Doppler flowmetry. PMID- 8361404 TI - Unplanned teen pregnancies subject of CURN scholar study. PMID- 8361405 TI - [Comparison of latex agglutination and coagglutination methods for the determination of bacterial antigens in cerebrospinal fluid]. AB - The latex agglutination and coagglutination tests were used to demonstrate specific bacterial antigens in cerebrospinal fluid of patients with bacterial meningitis. Latex agglutination was more sensitive than coagglutination. It detected 90% (18/20) of culture positive CSF specimens, whereas coagglutination detected 60% (12/20). Antigens were also detected by latex agglutination in seven of seven additional cerebrospinal fluid specimens after 32-48 hours of antimicrobial therapy, but four of seven by coagglutination. PMID- 8361406 TI - [Isolation of Gardnerella vaginalis from vaginal discharge specimens]. AB - In this study specimens taken from 93 patients who admitted to outpatient clinics of SSK Ankara Gynaecology and Obstetrics Hospital with vaginal discharge were examined for G. vaginalis, T. vaginalis, C. albicans and N. gonorrhoeae. We evaluated the smell, pH, direct microscopic examinations, stained preparations and specific culture results of the discharges which were taken from posterior fornix. We isolated G. vaginalis from 13 patients (13.9%), T. vaginalis from 5 patients (5.3%) and C. albicans from 19 patients (20.4%). N. gonorrhoeae could not be isolated from any of the specimens. In our control study, we isolated G. vaginalis in three out of 50 patients (6%) without vaginal discharge. We observed T. vaginalis in specimens of 3 control patients. C. albicans and N. gonorrhoeae could not be isolated in this study in this study. PMID- 8361407 TI - [Identification of dermatophytes as possible agents in clinically and microbiologically diagnosed dermatophytosis]. AB - In this study we have investigated the distribution of dermatophyte species clinically and microbiologically on 110 patients with dermatophytosis. The distribution of the dermatophytes according to the localization sites are: Tinea Capitis 13 (11.8%), T. Corporis 12 (10.9%), T. Inguinalis 22 (20%), T. Pedis et Manum 47 (42.7%), T. Unguinum 16 (14.5%). The species of dermatophytes which have been cultured were, Trichophyton rubrum 32 (29%), T. mentagrophytes 32 (29%), T. schoenleini 4 (3.6%), T. tonsurans 1 (0.9%), Epidermophyton floccosum 16 (14.5%), Microsporum canis 1 (0.9%), M. audouini 1 (0.9%), various molds 3 (2.7%) and also number of negative cultures obtained were 20 (18.1%). PMID- 8361408 TI - [The effect of calcium ions on the activation of Escherichia coli hemolysin]. AB - The calcium requirement for hemolytic activity Escherichia coli hemolysin is controversial. Thus, we aimed to study the calcium-dependent and independent hemolytic activity in an in vitro system. It was found that the free calcium in the cultivation medium might activate the hemolysin and once activated the hemolytic activity could not be inhibited by calcium chelator, EGTA. However, when the free calcium in the medium was chelated by EGTA before the inoculation of bacteria, the hemolytic activity was found to be almost entirely dependent upon the exogenous calcium supply to the test system. We also obtained some evidence showing that the calcium ions could take part in stabilization of this protein. PMID- 8361409 TI - [The effect of the inoculum concentration on the in vitro sensitivity of Pseudomonas aeruginosa]. AB - Using a broth microtiter dilution method, the minimum inhibitory concentrations of antipseudomonal antibiotics were determined against 19 P. aeruginosa isolates. Two different concentration of inoculum, 10(5) and 10(8), were used to show the inoculum concentration effect of in vitro antibiotic susceptibility tests. On the basis of the MIC values and using Howard B.J. (1) breakpoints, the effect of inoculum density was most prominent for amikacin and aztreonam, intermediate for mezlocillin, ticarcillin, piperacillin, cefotaxime, cefoperazone, netilmicin, tobramycin, gentamicin, and least apparent for ciprofloxacin and carbenicillin respectively. PMID- 8361410 TI - [In vitro susceptibility to cefoperazone and sulbactam/cefoperazone combination of bacterial strains isolated from various patient materials]. AB - Susceptibility of 110 bacterial strains isolated from clinical materials to Cefoperazone (CPZ) and Sulbactam/Cefoperazone (SBT/CPZ) combination was investigated and every strain was examined for beta-lactamase activity. Total beta-lactamase positivity rate was 40.9%. Antibacterial activity of SBT/CPZ combination was found to be higher than CPZ alone, especially on beta-lactamase producing bacteria. PMID- 8361411 TI - [Antimicrobial sensitivity of some gram-negative bacterial strains causing hospital or community-acquired infections]. AB - The susceptibility to various antimicrobics of E. coli, Klebsiella, S. typhimurium, Pseudomonas, Proteus and Edwardsiella strains causing hospital or community acquired infections were investigated by Kirby-Bauer's disk diffusion method. It was found that ampicillin was the least and quinolones were the most effective antimicrobics for the both hospital and community acquired infections. In general, the antimicrobic resistance was significantly increased for the hospital isolates. PMID- 8361412 TI - [Ofloxacin treatment of salmonella infections]. AB - In the present study, 33 adult patients with salmonella infections consisting of 13 typhoid fever, 9 paratyphoid fever, 8 enterocolitis, 2 carriers, 1 acute gastroenteritis have been treated with ofloxacin. The duration of treatment was 10 days for typhoid fever, 7 days for paratyphoid fever, 5 days for enterocolitis, 3 days for acute gastroenteritis and 7 days for asymptomatic carriers. All the patients recovered without any complication and fever declined to normal levels within a mean of 3.0 +/- 1.34 days. Two carriers of S. enteritidis became salmonella free after 7 days of ofloxacin treatment. One of the patients who had severe S. paratyphi B bacteremia remained carrier for about 6 months. None of the patients have relapsed. The antibiotic therapy proposals on salmonella in adults were discussed in the light of our results and the other studies. PMID- 8361413 TI - [Demonstration of Chlamydia trachomatis IgG using ELISA in transsexuals and homosexuals]. AB - In this study, 27 sera samples collected from transsexuals and homosexuals have been searched for Chlamydia trachomatis IgG antibodies with ELISA. Anti-Chlamydia IgG have been found positive in 18 cases (66.7%). In our study group there were no clinical symptoms except one case of transsexuals. Seropositivity rate of homosexuals (8/15) and transsexuals (10/12) were found to be important for transmitting the disease. PMID- 8361414 TI - [Relationship of histocompatibility groups to chronic HBV infections]. AB - HLA-A, B, C and DR locus specificities studied in 168 patients (71 Chronic active Hepatitis, 97 Chronic Persistent Hepatitis) serologically and histopathologically proven Chronic Hepatitis B Virus infection. There were 113 men and 55 women with a mean age of 23.2 (21-52) years. Hundred and seventy four healthy subjects (107 men, 67 women) included in control group with a mean age of 26.4 (20-54) years. The frequency of HLA A3 (p < 0.01), HLA A11 (p < 0.01), HLA B35 (p < 0.05) and HLA B51 (p < 0.01) were significantly higher in patients than in healthy control subjects. Comparisons among the other HLA-A, B, C and DR locus were found to be statistically non-significant. PMID- 8361415 TI - [Chlamydia trachomatis IgA and IgG antibodies in prostitutes and women having spontaneous abortion]. AB - In this study, the sera taken from 34 prostitutes, 34 women having spontaneous abortion and 34 control group were tested for C. trachomatis IgA and IgG antibodies. C. trachomatis antibodies were found positive in 30 (88.2%) of prostitutes, 11 (32.3%) of women having spontaneous abortion, 9 (26.4%) of controls. When the positivity rate of prostitutes and women having spontaneous abortion compared with control groups statistically, it was found significant in prostitutes (p < 0.05), but not found significant in women having spontaneous abortion (p > 0.05). PMID- 8361416 TI - [Actinomycosis abscess developing in the rectus muscle. (One case history)]. AB - A 36 year old male patient having an abscess in right rectus muscle's cover 2 years after stomach operation; attended to our hospital. The abscess was discharged. Following this, at 6 months intervals new abscess were formed in left lower and right upper rectus cover and discharged. Samples from abscess were routinely observed microbiologically and for tuberculosis; but the etiologic agent could not be identified. Six months later the patient attended to our hospital with abscess in right lower rectus cover again. The sample taken from the patient was examined thinking actinomycosis. After clinical and microbiological observation, the causative agent was identified as Actinomyces israeli. PMID- 8361418 TI - Childhood hyperactivity. PMID- 8361417 TI - [The role of Helicobacter pylori in the etiology of peptic ulcer and its therapy]. AB - The isolation of Helicobacter pylori from human gastric mucosa by Warren and Marshall in 1984, has given new approaches in etiology of peptic ulceration. Approximately all of duodenal ulcer patients have displayed antral gastritis with Helicobacter pylori, made strong suspicion of the bacteria in the etiology of duodenal ulcer. In therapy, combination of antibiotics to acid suppressive therapy should be preferred to antibiotics only. PMID- 8361419 TI - What have we learned from meta-analysis? PMID- 8361420 TI - The emergence of graduate medical schools in Australia. PMID- 8361422 TI - Desktop publishing and the author's disk. PMID- 8361421 TI - The stakes are high in public health. PMID- 8361423 TI - Football injuries in Australia at the elite level. AB - OBJECTIVE: To determine injury profiles for the elite level competitions of football played in Australia. DESIGN: Over the 1992 seasons, all injuries were prospectively recorded from 26 clubs in football competitions which included the Australian Football League (AFL), New South Wales Rugby League (NSWRL) and New South Wales Rugby Union (NSWRU). RESULTS: Some 2398 injuries were reported. In Australian Rules football, the most common injury was the hamstring tear (13%); this also accounted for the most time missed due to injury (16%). In rugby league and union, the most common injuries were head and facial lacerations (11% and 20%) followed by concussion (8% and 5%). The injuries accounting for most time missed were fractures and knee ligament injuries in the rugby codes. In Australian Rules football there were more lower limb muscle strain injuries, a high proportion of which were recurrences, with a significant incidence during training sessions. In the rugby codes, minor injuries to the head and neck were more common, particularly in forwards. While rugby league players suffered the most injuries, AFL injuries were on average more severe and consequently the total time missed through injury by players in these two codes was very similar. Rugby union had a significantly lower injury prevalence at the elite club competition level than rugby league or Australian Rules football. CONCLUSION: Injury rates in the elite football competitions are high, warranting ongoing analysis and further study in particular areas. PMID- 8361424 TI - Australian Rules football injuries in children and adolescents. AB - OBJECTIVE: To ascertain the incidence, severity, risk factors, and outcomes of injuries in children and adolescents playing Australian Rules football. DESIGN: SETTING AND SUBJECTS: A prospective cohort study of football injuries in children and adolescents playing community football. We studied a stratified random sample of 54 teams and clinics (18 under-15 teams, 18 under-10 teams and 18 Vickick clinics for children under 10 years) from the Melbourne metropolitan area. Football exposure, injuries and associated risk factors were recorded for 1253 players during the 1992 football season. RESULTS: Vickick, a modified form of the game, had the lowest rates of injury for all levels of injury severity, with an overall rate of 3.49 injuries per 1000 player-hours. The rate in the under-10 age group was 2.4 times higher (95% confidence interval [CI], 1.5-3.8) than that in Vickick, and the under-15 rate was 1.2 times (95% CI, 0.9-1.6) that of the under 10s. The under-15 age group had significantly more injuries that led to use of health services than the under-10 and Vickick groups, with rates of 3.93 (95% CI, 2.9-4.9), 0.64 (95% CI, 0.2-1.4), and 0.33 (95% CI, 0.1-0.8) injuries per 1000 players-hours respectively. Injuries were largely to soft tissues (sprains 26%, haematomas 25%) and to the lower limb (43%). Very few serious injuries occurred (19 fractures and three injuries with loss of consciousness); nearly all of these were in the under-15s. Rule modifications in under-10 teams and clinics were associated with an injury rate of 5.8 injuries per 1000 player-hours (95% CI, 4.4 7.3) compared with 7.5 injuries per 1000 player-hours (95% CI, 5.2-9.8) when no modification was used. Alterations to the ruck contest, decreased contact, field size and player numbers were significantly associated with lower injury rates, while body size was not. Of the 30% of injuries resulting in a health service consultation, the most common health provider was a medical practitioner. Very few required expensive investigation or treatment. CONCLUSION: Injury rates were low in children under age 10, but higher in adolescents. Most injuries were minor, and did not result in a health professional consultation. Rule modifications were associated with substantially lower injury rates at the under 10 level, and should be promoted as a safe way to learn football skills. PMID- 8361425 TI - Domestic violence victims in a hospital emergency department. AB - OBJECTIVE: To determine the prevalence and predictors of domestic violence victims among attenders at the emergency department at Royal Brisbane Hospital in 1991. DESIGN: Cross-sectional study in which randomly selected nursing shifts were used to screen attenders. RESULTS: Of all attenders at the emergency department, 14.1% disclosed a history of domestic violence. Women were more likely than men to disclose domestic violence ("raw" relative risk, 2.31; 95% confidence interval [CI], 1.83-2.91; relative risk adjusted for age and history of child abuse, 4.50; 95% CI, 3.02-6.71). The greatest risks for being an adult victim of domestic violence were being female and having experienced abuse as a child. Most of those who had experienced domestic violence within the last 24 hours (1.1% of attenders) came to the department after-hours when social work staff were unavailable for referral. CONCLUSIONS: The prevalence and risk factors have implications for the training of doctors and nurses in domestic violence problems and for the provision of adequate resources to deal with the psychosocial aspects of domestic violence. PMID- 8361426 TI - Hospital admissions and attendances for asthma--a true increase? AB - OBJECTIVE: To compare the ratio of hospital admissions for asthma to total hospital admissions and to admissions for non-asthma respiratory conditions, over an 11-year period, to see if there has been a true increase in admissions for asthma or merely a change in diagnostic labelling. A similar comparison was made for presentations with asthma and non-asthma respiratory conditions to the accident and emergency department. DESIGN AND SETTING: A case review of all patients with a confirmed diagnosis of respiratory disease admitted to hospital or attending the accident and emergency department at the Camperdown Children's Hospital between 1979 and 1989. RESULTS: There was a 98% increase in the number of patients admitted with a confirmed diagnosis of asthma. While the ratio of admissions for asthma to total admissions increased from 0.053 in 1979 to 0.09 in 1989, the ratio of admissions for non-asthma respiratory conditions to total admissions remained relatively constant. The ratio of attendances for asthma to total accident and emergency attendances rose from 0.017 in 1979 to 0.072 in 1989, whereas the ratio of attendances for non-asthma respiratory conditions to total accident and emergency attendances had a maximum variation of 0.065 to 0.09. CONCLUSIONS: These results suggest that there has been a major increase in the number of cases of asthma being treated at this hospital and that this is a true increase, perhaps representing increased severity, rather than a change in diagnostic labelling. PMID- 8361427 TI - Hepatitis B in urban Australian schoolchildren. No evidence of horizontal transmission between high-risk and low-risk groups. AB - OBJECTIVE: To document the prevalence of hepatitis B virus (HBV) infection in urban Australian primary schoolchildren, and to look for evidence of horizontal transmission of HBV in schools between children at high risk of infection and those at low risk. We compared the prevalence of infection in a group of low-risk children attending control schools (less than 5% of students from high-risk groups) with the prevalence in low-risk children attending test schools (more than 20% of students from high-risk groups). METHODS AND RESULTS: Venous blood was collected and tested for hepatitis B markers by radioimmunoassay; 2883 children (1431 boys) of mean age 11.3 years (SD, 0.7) from 50 schools were tested. Evidence of past or current infection was present in 169 children (5.9%). This number comprised three of the 1347 low-risk children (0.2%), 10 of the 602 medium-risk children (1.7%), 154 of the 731 high-risk children (21.1%) and two of the 203 other children (1%). Fifty-four of the 169 infected children were hepatitis B surface antigen (HBsAg) positive, 36 of the 54 were also positive for hepatitis B e antigen (HBeAg). There was no difference between children in the low-risk group in test and control schools for markers of hepatitis B virus infection. CONCLUSIONS: A low prevalence of HBV infection was found in low-risk school-children irrespective of the proportion of high-risk children in their classes. Targeting vaccination to infants and children with known risk factors is the most important strategy in low endemicity countries; vaccination of children without risk factors could be delayed till early adolescence. PMID- 8361428 TI - Skin diseases in the tropics. AB - Australian physicians may encounter a number of tropical skin diseases. Migrants or visitors may travel here with a skin disease, or people living in the tropical or subtropical regions of Australia may develop skin conditions. The most important of these are cutaneous leishmaniasis, cutaneous amoebiasis, tinea imbricata, favus, sporotrichosis, chromomycosis, cutaneous tuberculosis, Buruli ulcer, cutaneous larva migrans and dracontiasis. PMID- 8361429 TI - Leprosy in the tropics and Australia. AB - Leprosy is no longer the feared disease of the past, but it still causes significant morbidity in countries where it is endemic, and it is estimated that up to 2500 million people are at risk of contracting the disease. Control with dapsone monotherapy over the past 20-30 years has been effective in some countries but secondary and, more recently, primary drug resistance is now widespread. This situation prompted the development of multidrug therapy regimens which are proving highly effective. Here the natural history and clinical features are described, as well as the history and impact of leprosy in Australia. Early diagnosis and the current multidrug regimens offer hope for long term control of the disease. PMID- 8361430 TI - Intra-arterial streptokinase in acute ischaemic stroke. A pilot study. AB - AIMS: To assess the safety and efficacy of the intra-arterial administration of streptokinase within 24 hours of acute ischaemic stroke. METHODS: Patients who presented to the Austin Hospital casualty department between 3 and 22 hours after an acute stroke were considered for the study. Eligible patients had pretreatment non-contrast computed tomographic scans of the brain to exclude haemorrhage. Streptokinase (250,000 units) was administered directly into the common carotid artery or the cervical portion of the internal carotid artery. MAIN OUTCOME MEASURES: The incidence of symptomatic and asymptomatic cerebral haemorrhage, haemorrhagic transformation of infarction, angiographic reperfusion, clinical outcome at seven to 10 days and the frequency of other complications. RESULTS: Thirteen patients were treated over a 16-month period. Major clinical improvement occurred in five patients (39%) at 48 hours. This was associated with angiographically demonstrated recanalisation of a middle cerebral artery occlusion in two patients and partial recanalisation in two others. Significant hypotension in two patients required therapy to be stopped. In five other cases mild hypotension developed but the streptokinase infusion was completed. Haemorrhagic transformation of the infarct occurred in four patients without clinical deterioration. CONCLUSION: Intra-arterial administration of streptokinase is safe in selected patients with acute ischaemic stroke. The theoretical benefit of an increased local thrombolytic effect and reduced systemic complications, compared with the use of higher intravenous doses, justifies a randomised clinical trial. If therapies such as this are to be successful, rapid referral to an appropriate centre is necessary. PMID- 8361432 TI - Prevention of HIV and HBV transmission in general practice. PMID- 8361431 TI - Albuminuria in aborigines and Europids of south-eastern Australia. AB - OBJECTIVE: To determine the prevalence of albuminuria in Aborigines and Australians of European descent (Europids), as part of an epidemiological study of glucose intolerance and cardiovascular risk factors based in country towns of south-eastern Australia. DESIGN: Population-based cross-sectional study, with Aborigines and Europids of south-eastern Australia as the reference populations. METHOD: Random urine samples were collected from people aged > or = 35 years, and tested with Albuscreen (a test kit sensitive to urinary albumin concentrations of 0.03 g/L) and two other methods in the field. The samples were later analysed for the calculation of urinary albumin:creatinine ratios, which were then categorised according to cut-off points for abnormal renal function that have been proposed in the literature. RESULTS: Three hundred and six Aborigines and 553 Europids participated, with response rates of 90% and 94% respectively. According to Albuscreen, albuminuria was more common in Aborigines than in Europids. In men, 36% (95% confidence interval [CI], 20%-52%) of Aborigines exceeded the albumin concentration of 0.03 g/L, compared with 14% (CI, 9%-19%) of Europids (P < 0.01); in women, 39% (CI, 27%-51%) of Aborigines exceeded 0.03 g/L, compared with 18% (CI, 12%-24%) of Europids (P < 0.01). Sixty-one per cent (CI, 44%-78%) of Aboriginal men had a urinary albumin:creatinine ratio of > or = 1.30 mg/mmol, compared with 12% (CI, 7%-17%) of Europid men (P < 0.01); 56% (CI, 44%-68%) of Aboriginal women exceeded this cut-off point, compared with 23% (CI, 16%-30%) of Europid women (P < 0.01). CONCLUSION: A higher prevalence of renal disease in the Aboriginal population of south-eastern Australia is expected. Risk factors for renal disease in Aborigines throughout Australia require elucidation. PMID- 8361433 TI - A report of human parvovirus B19 infection in hydrops fetalis. First Australian cases confirmed by serology and immunohistology. AB - OBJECTIVE: To present the first Australian cases of fetal hydrops induced by parvovirus B19. CLINICAL FEATURES: Autopsies on two cases of intrauterine fetal death with hydrops fetalis and pallor revealed evidence of myocarditis and widespread characteristic inclusion-bearing cells, predominantly erythroblasts. The diagnosis of hydrops fetalis induced by parvovirus B19 was confirmed in both cases by immunohistological localisation of the viral inclusions by means of a monoclonal antibody to the VP1 and VP2 proteins of parvovirus B19. A low level of parvovirus B19 IgM antibodies was detected in the second case. CONCLUSIONS: It is possible that our relatively small population and lack of familiarity with the histopathological features may have led to underdiagnosis rather than a true absence of fetal parvovirus B19 infection in Australia. The condition can be diagnosed and treated antenatally and therefore should be included in the differential diagnosis of causes of hydrops fetalis. PMID- 8361434 TI - Do the teaching hospitals of the University of Queensland really want a four-year medical course? A guarded yes. AB - OBJECTIVE: To gauge the measure of support among clinical teaching staff for the University of Queensland's proposals to introduce a four-year graduate entry integrated medical curriculum. SETTING: The three largest teaching hospitals of the University of Queensland Faculty of Medicine. METHODS: A questionnaire was sent to 565 consultants and 493 junior medical staff regarding deficiencies of the present six-year course, deficiencies in present methods of selecting students, and possible solutions. RESULTS: 154 (68%) full-time consultants, 174 (51%) visiting consultants and 197 (40%) junior staff replied. Ninety per cent of the consultants and 60% of the junior staff were current teachers. Respondents strongly supported the need for major change, the integration of biomedical sciences into clinical teaching and the use of problem-based learning. Regarding selection, over 80% of respondents considered graduate entry to have no advantage over undergraduate entry, but there was strong support for an external examination including sciences. There was also strong support for broadening entry criteria to include common sense, motivation and empathy. Seventy-two per cent of consultants and 82% of juniors opposed the proposals in their present form. However, 52% of consultants (but only 23% of juniors) would support the concept of a four-year integrated course if the issue of selection criteria could be resolved. CONCLUSION: A majority of consultants support the concept of a four year integrated curriculum which uses problem-based learning methods. They do not support the proposed selection criteria based upon graduate entry, but would support a predominantly science-based selection process, not necessarily restricted to graduate applicants, but incorporating broader personal characteristics than are used at the present time. PMID- 8361435 TI - Frequency of bleeding in football. PMID- 8361436 TI - Rare disease surveillance in children. PMID- 8361437 TI - Recurrent bacterial meningitis associated with strongyloides hyperinfection. PMID- 8361439 TI - Dry mouth in HIV infection. PMID- 8361438 TI - Redbacks re-visited. PMID- 8361440 TI - Thiamine anaphylaxis. PMID- 8361441 TI - Heat treatment at 100 degrees C of factor VIII and IX coagulation factor concentrates. PMID- 8361442 TI - Vigabatrin in drug-resistant epilepsy. PMID- 8361443 TI - Ambient environment may affect saliva ferning fertility test. PMID- 8361444 TI - Hereditary factors in strabismus. PMID- 8361445 TI - Laparoscopic cholecystectomy. PMID- 8361446 TI - Guidelines: dying with dignity. PMID- 8361447 TI - The potential for elderly donors to increase renal transplantation rates in Australia. PMID- 8361448 TI - The reform of medical education. PMID- 8361449 TI - Addison's disease in the acquired immunodeficiency syndrome. PMID- 8361450 TI - Medical management of miscarriage with RU486. PMID- 8361451 TI - Tacrine for Alzheimer's disease. PMID- 8361452 TI - Ketorolac for seasonal allergic conjunctivitis. PMID- 8361453 TI - Influenza vaccine, 1993-1994. PMID- 8361454 TI - International Society of Pediatric Oncology (SIOP) XXV Meeting. San Francisco, California, October 5-9, 1993. Abstracts. PMID- 8361455 TI - Public health focus: physical activity and the prevention of coronary heart disease. AB - Coronary heart disease (CHD) is the leading cause of mortality in the United States: each year, CHD is newly diagnosed in approximately 1.5 million persons and accounts for an estimated $47 billion in direct and indirect health-care costs (1). Multiple risk factors associated with CHD include genetic susceptibility, elevated serum cholesterol, low levels of high-density lipoprotein cholesterol, cigarette smoking, uncontrolled hypertension, obesity, diabetes mellitus, and physical inactivity (2). This report summarizes information about the potential efficacy and cost-effectiveness of physical activity promotion as a strategy for preventing CHD. PMID- 8361456 TI - Handwashing and glove use in a long-term-care facility--Maryland, 1992. AB - Residents of long-term-care facilities (LTCFs) are at risk for acquiring facility associated infections and consequent mortality (1,2). Despite this risk, no national guidelines exist for infection-control practices in LTCFs, and information regarding the nature of infection-control practices in LTCFs is limited. To evaluate glove use and handwashing practices in an LTCF, and to determine factors associated with compliance with infection-control policies and the frequency of microbial transmission, Maryland Department of Health and Mental Hygiene (DHMH) and CDC staff observed glove use and handwashing practices on a chronic-care ward of an LTCF in Maryland for a 1-month period during 1992. This report summarizes the findings of this study. PMID- 8361457 TI - Alcohol use and aquatic activities--United States, 1991. AB - Drowning, a leading cause of death from unintentional injury in the United States, accounted for approximately 4600 fatalities in 1991 (1,2). Although 25% 50% of adolescents and adults who drowned had consumed alcohol near the time of death (3), information regarding drinking behaviors during aquatic activities is limited. To assist in refining strategies for prevention of alcohol-related injury in aquatic settings, during July 15-September 30, 1991, the Boston University School of Public Health surveyed a national sample of adolescents and adults regarding their participation in aquatic activities and associated alcohol use. This report summarizes these findings. PMID- 8361458 TI - Characteristics of death certifiers and institutions where death is pronounced- Fulton County, Georgia, 1991. AB - Information from death certificates (DCs) is used to measure health status and to set public health priorities at all levels in the United States. However, because of limitations in the training of physicians who certify deaths, the completeness and accuracy of cause-of-death information varies (1-3). To develop a basis for targeting education of physicians who certify deaths, CDC, in cooperation with the Fulton County (Georgia) Vital Records Office, reviewed a consecutive series of 500 DCs filed in Fulton County (1990 population: 648,951) from April 10 through May 2, 1991, to characterize the number and proportion of personal physicians (PPs) (defined as physician certifiers not acting in the capacity of medical examiners or coroners [MECs]) and MECs certifying death, as well as other factors. This report summarizes the results of that review. PMID- 8361459 TI - Adult blood lead epidemiology and surveillance--United States, second quarter, 1993. PMID- 8361460 TI - New pediatric formulation of Recombivax HB. PMID- 8361461 TI - Influenza A outbreaks--Louisiana, August 1993. AB - In August 1993, the Louisiana Department of Health and Hospitals (LDHH) investigated reports of acute respiratory illness among residents of two nursing homes and workers on a dredging barge in southern Louisiana; influenza type A has been confirmed as the cause of these outbreaks. This report summarizes the investigations of the outbreaks. PMID- 8361462 TI - Behavioral Risk Factor Surveillance System--Michigan, 1987-1991. AB - A national health objective for the year 2000 is to implement periodic analysis and publication of each state's progress toward the objectives for each racial/ethnic group that constitutes at least 10% of the state's population (objective 22.5a). In Michigan (1990 population: 9.3 million), blacks represent approximately 12% of the adult population*; prevalence estimates for risk factors for the black population derived from the Behavioral Risk Factor Surveillance System (BRFSS) have varied in consistency because of the limitations of small sample sizes. To improve the precision of risk factor prevalence estimates for blacks in Michigan and to improve measurement of the state's progress toward the national year 2000 objectives for blacks, in 1993, the Michigan Department of Public Health (MDPH) aggregated annual state BRFSS data for 1989-1991. This report summarizes the findings of this analysis and compares them with an analysis of annual state BRFSS data for 1987-1991. PMID- 8361463 TI - Tuberculosis morbidity--United States, 1992. AB - In 1992, 26,673 cases of tuberculosis (TB) (10.5 cases per 100,000 population) were reported to CDC from the 50 states, the District of Columbia, and New York City, a 1.5% increase over the number reported in 1991 (26,283 [10.4 cases per 100,000]). In addition, 370 cases were reported from Puerto Rico (312) and the U.S. territories (58). This report summarizes final TB surveillance data for 1992 and compares findings with previous years. PMID- 8361464 TI - Public health focus: impact of safety-belt use on motor-vehicle injuries and costs--Iowa, 1987-1988. AB - Each year in the United States, motor-vehicle-related trauma results in approximately 40,000 deaths, 5.4 million nonfatal injuries, and $15.4 billion in direct medical costs and costs of emergency services. The use of safety belts reduces the number and severity of injuries from motor-vehicle crashes, and since states began enacting safety-belt laws, the prevalence of safety-belt use in the United States has increased substantially. In Iowa, where a safety-belt use law was enacted in 1986, the observed rate of safety-belt use increased from 18% in 1985 to 55% in 1988. Data from the Iowa Safety Restraint Assessment were used to estimate the effect of this increase on injury severity and hospital costs and to estimate the statewide savings in direct costs (i.e., hospital and professional fees) and indirect costs (i.e., administrative costs and loss of productivity) for 1 year. This report summarizes the findings of this study. PMID- 8361465 TI - Update: hantavirus-associated illness--North Dakota, 1993. PMID- 8361466 TI - Sensitivity of the test for antibody to hepatitis B surface antigen--United States. AB - Beginning in March 1986, some test kits for antibody to hepatitis B surface antigen (anti-HBs) were modified to increase sensitivity, and new anti-HBs tests were introduced with increased sensitivity for detecting anti-HBs. To assess the impact of this increased sensitivity on the interpretation of hepatitis B postvaccination testing results, the Food and Drug Administration (FDA) conducted a study of currently distributed anti-HBs test kits to determine the lower limits of their sensitivity relative to the World Health Organization (WHO) Anti-HBs Reference Preparation. In addition, CDC conducted a study among a group of vaccinated public safety workers to determine the positive predictive values of the current anti-HBs tests when used to evaluate immunity after hepatitis B vaccination. This report provides background to and summarizes the results of these two studies. PMID- 8361467 TI - [Usefulness of subtotal colectomy with colorectal anastomosis for chronic ulcerative colitis]. AB - Recently in Japan, most of surgeons have been performing restorative proctocolectomy with ileoanal anastomosis for ulcerative colitis, leaving unsolved problems with regard to postoperative complications. Analysis was made on subtotal colectomy with colorectal anastomosis with the following policies. Firstly, the inflammation of the remnant intestine could be easily and correctly controlled by medication in outpatient. Secondly, carcinomas associated with ulcerative colitis can be discovered by postoperative colonoscopic examinations. Operations were carried out to 26 cases of ulcerative colitis for the past 13 years. Subtotal colectomy with colorectal anastomosis were performed to 11 cases. Three cases of colorectal carcinomas associated with ulcerative colitis were experienced. One of the resected specimen was investigated using stereomicroscopy after alcian blue staining to formalin fixed one. As a result of this research, we have convinced that colorectal anastomosis should be favorable surgical potion to the cases of chronic ulcerative colitis because postoperative anal function and quality of life are excellent in our series, in addition, carcinomas in the remnant intestine can be probably easily found out at the early stage by annual colonoscopic examinations with dye staining. PMID- 8361468 TI - [Anatomical measurements of the internal anal sphincter--the relative site of the dentate line in the internal anal sphincter]. AB - Not only the length and the width of the internal anal sphincter but also the relative site of the dentate line in the internal anal sphincter were investigated in 62 resected specimens obtained by abdominoperineal resection of the rectum for malignancy. Mean length and width of the internal sphincter were 25.8 +/- 4.1mm (mean +/- standard deviation) and 4.0 +/- 1.1mm, respectively. The length of the internal sphincter from its distal end to the level of the dentate line was 11.3 +/- 3.1mm, which corresponded to 44% of the total length of the internal sphincter. The individual difference in the site of the dentate line in the internal sphincter was objectively demonstrated. It seems to be therefore important to modulate the extent of sphincterotomy in order to minimize postoperative anal dysfunction on the surgery for fissure or fistula-in-ano, in which sphincterotomy is widely practiced up to the level of the dentate line. PMID- 8361469 TI - [Therapeutic plasmapheresis to treat postoperative hepatic failure clinical course and therapeutic outcome in Japan]. AB - The most serious hepatic complication after surgical procedure is postoperative hepatic failure. There is no therapy for this condition except plasma exchange. Precise clinical definition of postoperative hepatic failure was discussed based on a questionnaire distributed by the association in 1989, and in 1991 by the working group. Giving special consideration to the use of therapeutic plasmapheresis, the clinical definition of postoperative hepatic failure was established as hepatic injury after surgery, without obstructive causative factors, laboratory values for total bilirubin over 5mg/dl with continuous elevation, and hepaplastin activity under 40%. Key factors in determining initiation, efficacy, and cessation of plasmapheresis were coma grade (II-III), total bilirubin levels, and the activities of coagulation tests. The majority of underlying diseases were hepato-biliary in nature. The causative factors of hepatic injuries were massive bleeding and infection. The morbidity was estimated at 600 to 3000 cases/year. The frequency of plasma exchange was one session every/1.4-1.6 days. The volume of exchanged fresh frozen plasma was about 3292 ml/a session. Nafamostat mesilate was used as an anticoagulant. The survival rate was 14% to 40%. Earlier initiation of plasma exchange is indicated. PMID- 8361470 TI - [Experimental study of liver regeneration and tumor growth following partial hepatectomy]. AB - An experimental study was performed aiming to clarify the mechanism of early recurrence of hepatocellular carcinoma following hepatectomy. AH109A ascites hepatoma cells were implanted in a liver or subcutaneous tissue of male Donryu rats 5 days prior to 70% partial hepatectomy (H group) or simple laparotomy (L group) or non operation control (C group). Rats were sacrificed at 1, 3, 7 postoperative days. Tumor size, labelling index (LI), tissue blood flow (TBF) and regeneration rate of the remnant liver were measured. Tumor size of the remnant liver in hepatectomy group was 492 +/- 117 mm3 against 129 +/- 63 mm3 in laparotomy group showing enhancement of tumor growth following partial hepatectomy with statistical significance (p < 0.01). On the contrary, there was no difference in the growth of subcutaneous tumor among H, L, C group. A significant increase of LI in both liver and subcutaneous tumor cells comparable to regenerating liver cells at 24 hours after hepatectomy was observed in H group. It suggests that some humoral hepatotrophic factors increased DNA synthesis of not only tumor cells but liver cells. TBF in the tumor and remnant area of the liver were increased. This result supports that increased hepatotrophic factors and TBF led to the enhancement of tumor growth in the remnant liver following partial hepatectomy. PMID- 8361471 TI - [Modes of spread and surgical strategy for gallbladder carcinoma with subserosal invasion]. AB - The mode of spread and the prognosis were investigated in 22 patients with resected gallbladder carcinoma invading the subserosal layer. By the Kaplan-Meier method, the 5-year survival rate was 68.8% in patients receiving curative or relatively noncurative resection. On the other hand, no patient survived for more than 3 years after noncurative resection. The mode of subserosal infiltration was classified according to the general rules for gastric cancer study. At least systemic lymph node dissection (R2) should be performed in patients with ss alpha cancer, because lymph node metastasis in these patients were confined to the 1st group. More extensive lymph node dissection (R2 with 9, 16) is essential for patients with ss beta and ss gamma, because lymph node metastasis to at least the 2nd group were seen in 75% of them. The surgical margin was positive for cancer in all patient with infiltration of the hepatoduodenal ligament. Therefore, it was considered that hepatoligamentectomy should be performed in these patients to obtain a cancer free surgical margin. Among patients undergoing curative or relatively noncurative resection, the recurrence rate was 43% in those with lymph node metastasis and 50% in those with DNA aneuploidy. Therefore, it appears that adjuvant chemotherapy should be given to such patients. PMID- 8361472 TI - [Hormone therapy of tamoxifen in resected carcinoma of the pancreas]. AB - Greenway et al reported estrogen receptor existed in the carcinoma of the exocrine pancreas in 1981. We followed the study by using immunohistochemical method with monoclonal antibody ER-D5 (Amersham) and found high levels of estrogen receptor in 21 cases out of 27 carcinomas of the pancreas (77.8%). Furthermore, we gave randomly the hormone therapy by Tamoxifen 20 mg per day adding to immuno-chemotherapy (Tegaful, Mitomycin, Krestin, OK-432) to the patients with resected carcinoma of the pancreas. There was no significant difference of the survival rate of pancreatic carcinoma without hormone therapy between 10 cases with estrogen receptor and 4 cases without estrogen receptor at the 6th month and 12th month. However, in cases treated by Tamoxifen, remarkable high survival rate at 12 months of 11 cases with estrogen receptor was obtained to be 85.7% according to Kaplan-Meier method. Two cases without estrogen receptor died within 5 months. One year survival rate of Tamoxifen group (13 cases) was 78.6% and that of non Tamoxifen group (14 cases) was 21.4%. These findings indicated that estrogen receptor existed at the high level in the carcinoma tissues of the pancreas and anti-estrogen treatment might offer a new approach to the treatment of pancreatic carcinomas. PMID- 8361473 TI - [Experimental study of multi-visceral transplantation in dogs]. AB - The purpose of the present study was to examine the technical, functional and immunologic aspects in the multivisceral transplantation using canine model. After removal of upper abdominal organs en bloc, the composite graft including the liver, pancreas, spleen and duodenum was orthotopically transplanted in 35 dogs. Ten recipients survived more than 3 days, and 6 more than 6 days. Cause of early death was massive lymphatic leakage, and late death was due to acute rejection or other complications. As technical considerations, perfusion of the graft should be only via aorta to prevent pancreatic edema, and reperfusion should be at first with arterial blood flow to minimize the ischemic damage of the graft. Hepatic and pancrease-endocrine functions were recovered by 3 days, after grafting, and 2-3 days later pancreas-exocrine function was restored. Thereafter the hepatic function was progressively deteriorated again from 6 to 8th day, although the pancreatic function was well maintained until death. At autopsy this hepatic dysfunction was histologically confirmed to be caused by severe acute rejection. On the other hand, the pancreas and duodenum were morphologically almost normal. The results demonstrated the dissociation in functional recovery after grafting and extent of rejection reaction among each grafted organ in the multivisceral transplantation. PMID- 8361474 TI - [Full thickness chest wall resection for recurrent breast cancer with reference to prognostic factors]. AB - Full thickness chest wall resection surgery has been carried out in 16 patients with local recurrence after previous mastectomy. Seven of 16 patients had isolated chest wall recurrence, but 9 had mediastinal invasion and/or distant metastasis of carcinoma. Recurrent breast carcinoma involving the bony chest wall was resected, and the chest wall defects were reconstructed with myocutaneous flaps using rectus abdominis or latissimus dorsi, or breast flap. Marlex mesh was utilized under the flap in 10 patients. The 3 year survival probability was 79% and the 5 year one was 57% with mean follow-up period of 43 month. Local recurrence was classified into 3 types according to cancer infiltration; i.e., demarcated, scattered and diffuse types. The patients with demarcated type showed better prognosis than those with diffuse type. Patients who received curative surgery showed better prognosis than those receiving palliative surgery. A disease free interval (DFI) after mastectomy longer than 5 years correlated well with a long survival rate after chest wall resection. Thus, local recurrence presenting demarcated tumor with possible curative surgery as well as a longer DFI after mastectomy is a favorable prognostic factor for full thickness chest wall resection. PMID- 8361475 TI - [Results of arterial reconstruction in Buerger's disease]. AB - One hundred and eight bypass operations for Buerger's disease were performed between November 1976 and August 1990. The bypass procedures, prostheses, cumulative patency rate and the influence of smoking on the results were discussed. Five-year cumulative patency rate of Aorto-femoral bypass was 88.2%. Aorto-femoral bypass should be always indicated as a standard procedure for the iliac lesion in Buerger's disease, because the patency rate was very low in aorto iliac bypass group or ilio-femoral bypass group. Five-year cumulative patency rate of infrainguinal bypass using autogenous vein was 64.8%, and that in the patients who quit cigarette smoking was as high as to 73.3%. We should use autogenous vein as much as possible for infraiguinal bypass and discontinuance of cigarette smoking is considered to be one of the important factors to improve the patency rate in Buerger's disease. PMID- 8361477 TI - [The production of spontaneous liver metastasis model from colon carcinoma in nude mice: preliminary report]. PMID- 8361476 TI - [A case report of atypical Fabry's disease with colon cancer]. AB - An atypical case of Fabry's disease, a rare congenital disorder of glyco-lipid metabolism, associated with sigmoid cancer was reported. A 50-year-old man who had been diagnosed as having atypical form of Fabry's disease complained of lower abdominal pain and difficult defection. A barium enema and an endoscopic examination disclosed sigmoid colon cancer. The cancer was curatively resected. Fabry's disease is often associated with intestinal disease, but the patient with Fabry's disease associated with intestinal malignancy has not been reported. PMID- 8361478 TI - [Stimulation of tissue lipoprotein lipase activity in cancer cachectic rats: preliminary report]. PMID- 8361479 TI - [In vitro establishment of murine class II MHC antigen restricted autoreactive T helper cell clone and its antitumor effect: preliminary report]. PMID- 8361480 TI - [Three-dimensional angio-computed tomography of coronary arteries: preliminary report]. PMID- 8361481 TI - [Expression of elongation factor 1 gamma-related sequence in human gastric cancer: preliminary report]. PMID- 8361482 TI - [Tyrosine protein kinase: role in the process of activating lymphocytes]. AB - Some types of receptor and intracellular protein-tyrosine kinases are reviewed. These enzyme systems play an important role in activation of T- and B-lymphocytes and their precursors. The relationship is shown between the two main ways of lymphocyte activation: the phosphatidylinositol metabolic pathway, induced by protein kinase C, and the protein-tyrosine kinase pathway of intracellular protein and enzyme phosphorylation. PMID- 8361483 TI - [Genotoxic modification of nucleic acid bases and biological consequences of it. Review and prospects of experimental and computational investigations]. AB - The review is presented of experimental and computational data on the influence of genotoxic modification of bases (deamination, alkylation, oxidation) on the structure and biological functioning of nucleic acids. Pathways are discussed for the influence of modification on coding properties of bases, on possible errors of nucleic acid biosynthesis, and on configurations of nucleotide mispairs. The atomic structure of nucleic acid fragments with modified bases and the role of base damages in mutagenesis and carcinogenesis are considered. PMID- 8361484 TI - [Preparation of hybrid proteins consisting of human interleukin-2 and the cytotoxic A-subunit of Shigella toxin]. AB - Recombinant plasmids providing the synthesis of chimeric proteins consisting of amino acid sequences of human interleukin-2 (IL-2) and Shiga toxin cytotoxic A subunit (ILA and AIL chimeric toxins) were constructed. The ILA and AIL chimeric toxins were shown to inhibit protein synthesis in the rabbit reticulocytes cell free system. These chimeric toxins displayed two opposite activities of the constituent parts of their molecules on T-lymphocytes from the peripheral blood of healthy volunteers. Hybrid protein AIL (approximately 10(-6) g/ml) has caused the most significant depression of T-lymphoblast proliferation. PMID- 8361485 TI - [Use of a series of synthetic peptides and purified major histocompatibility complex I (H-2K(b)) molecules for inhibiting T-suppressors, specific for the K(b) molecule, and their induction by peptides in vivo]. AB - Six synthetic peptides of the MHC class 1 molecule corresponding to individual H 2kb participants in amino acid sequences of domains alpha 1 (peptide 1 and 2) and alpha 2 (peptide 3, 4, 5, 6) were selected. Kb-specific suppressor T cells (Ts) were in vivo in mice, then pretreated with a set of peptides and assayed by proliferation decrease in the third-partial mixed lymphocyte culture (MLC). Effector function of Ts was abolished by the complex of the alpha 2-domain peptides (but not by the alpha 1-domain peptides) and decreased by each peptide (4, 5, 6) of the alpha 2-domain. Both alpha 1 and alpha 2 domain peptides, added at high concentrations, decreased the otherwise efficient enrichment of Ts during the absorption-elution procedure on the syngeneic macrophage (MP) monolayers. A similar significant effect was observed the purified Kb molecule (100 mg/ml) on the allogeneic MP monolayer. Interaction between Ts receptors with some MHC peptides indicates effector Ts activation in vivo by induction with peptides 5+6 of the alpha 2 domain. The fine mechanisms of interaction between MHC class I molecule epitopes and T cell receptors (TCR) of each of the T cell subsets separately are under study now. PMID- 8361486 TI - [Nonenzymatic covalent modification of human hemoglobin by pyridoxal-5-phosphate under the effect of visible light]. AB - Under the action of visible light, PLP with apo-, oxy- and deoxy-Hb at 4-20 degrees C and neutral pH produced adducts stable to dialysis and Sephadex gel filtration. The stable adduct formation enhanced with an increase in radiation intensity and/or irradiation time. Under light, production of stable adducts occurred most effectively for apo-Hb and was significantly slowed down in the case of met-Hb as well as in the presence of an electron acceptor, methylene blue. PLP-Hb adducts possessed intense fluorescence coinciding in properties with the fluorescence of stable PLP adducts obtained after Schiff base reduction by NaBH4. Stable adduct formation is assumed to proceed owing to Schiff base aldimin link reduction by photoejected electrons. During isoelectrofocusing of hemoglobins which had formed stable adducts with PLP under light or after NaBH4 treatment of solutions, essentially the same pictures were observed as to the number of new bands and their position in the isoelectroforegram, with the band intensity being different. This is related to the distinctions in the electron seeking properties of the Schiff bases produced by PLP with alpha-NH2 groups of Val-1 and epsilon-NH2 groups of lysine residues of the protein alpha- and beta chains. PMID- 8361487 TI - [Calorimetric studies of the effect of amino acid replacements 16Gln-Leu and 26Tyr-Asp on the structural organization and stability of the Cro-repressor from phage lambda]. AB - The scanning calorimetry technique has been used to study the influence of amino acid substitutions on thermodynamic parameters of formation and stabilization of a cooperative structure of Cro repressor of bacteriophage lambda molecule. It is shown that substitutions 16Gln-Leu and 26Tyr-Asp enhances the protein molecule stability by 32 degrees C as compared with the wild-type protein. It is also demonstrated that the denaturation enthalpy of the mutated Cro differs slightly from that of the wild-type protein at the same temperature, while the effective enthalpy value is significantly lower. The analysis of excess heat capacity of the mutated protein shows that this complex function determined experimentally is approximated by two functions, which is indicative of the presence of two quasi independent transitions. Thus, the stabilization and redistribution of intermolecular interactions evoked by the above substitutions leads to disintegration of the single cooperative repressor molecule in two interacting cooperative domains. The plausible mechanism of formation of such a domain structure is discussed on the basis of the available calorimetric data. PMID- 8361488 TI - [Features of the biogenesis of Escherichia coli alkaline phosphatase during its supersynthesis]. AB - The oversynthesis of the secreted alkaline phosphatase (PhoA) in E.coli K12802 cells due to transformation with the PhoA+ plasmid pHI-7 leads to a change in its biogenesis--alternative localization and accumulation of the enzyme intermediate forms corresponding to different stages of the its post-translational modification. Instead of the soluble PhoA available in the parent strain mostly as a completely processed mature metazyme III localized in the periplasm, five enzyme forms were discovered in the PhoA overproducer: a cytoplasmic PhoA precursor (prePhoA) as insoluble aggregates; three soluble metazymes of a mature active form localized in the periplasm as in well as in culture medium; and a soluble high-molecular form in the periplasm. PrePhoA was isolated and purified by removal of soluble cell fractions using differential centrifugation, solubilization of membrane proteins with Triton X100, dissolution of the aggregates in the buffer with 8M urea and FPLC on MonoQ. Extracellular PhoA was purified by ultrafiltration, thermal treatment, and gel chromatography on Sepharose CL-4B. It was shown that the isolated prePhoA can be transformed into a mature form in the presence of a leader peptidase in 0.8 urea and is completely cleaved with proteinase K. Three forms of the mature PhoA vary in resistance to proteinase K and trypsin. Metazyme I, the unprocessed mature PhoA, is the most resistant to proteolysis. PMID- 8361490 TI - [Poly(U)-dependent interaction of yeast tRNA(Phe) and its fragments with Escherichia coli ribosomes. II. Localization of tRNA binding centers with a P site]. AB - Poli(U)-dependent binding of yeast tRNA(Phe) lacking the 3'-terminal CA or CCA residues, and fragments of tRNA prepared by splitting the tRNA(Phe) at the G18 or 7mG46 nucleotides, to the 70S ribosomal P-site was studied. Equilibrium binding constants and free energies of binding were measured. The contribution of C74 and C75 was estimated at 3.9 kJ/mol and 3.0 kJ/mol, respectively, at 10 mM Mg2+ and 30 degrees C. The free energies of the binding of the anticodon arm the tRNA lacking its CCA terminus, and the tRNA fragment containing bases N1-N45 were found to be nearly equal. These results indicate that only the anticodon arm and the CCA terminus take part in deacylated tRNA-P-site interaction. PMID- 8361489 TI - [Expression of the Oct-2 protein during cell differentiation in vivo and in vitro]. AB - The expression of an Oct-binding protein Oct-2 was studied during differentiation of three cell lines. Two inductors were used in our experiments: retinoic acid and DMSO. It was shown that all these cells have heterogeneous population of Oct 2 mRNA. Under differentiation the pattern of Oct-2 RNA and expression of active Oct-2 proteins was changed. PMID- 8361491 TI - [Expression of the gene for transforming growth factor type alpha, transferred into A431 cells by a recombinant retroviral vector]. AB - Cells of human epidermoid carcinoma A431 were used for obtaining of the cell line constantly expressing TGF-alpha. Recombinant virions were obtained by introducing the proviral DNA into PA317 cells by means of electrotransfection. A protein with the EGF-competing activity was found in a conditioned media of the chosen clone A431/1522-4. The concentration of this protein was several times higher than in a conditioned media of wild type A431 cells. By means of electrophoresis, isoelectric focusing, and immunochemical analysis it was shown that the protein is TGF-alpha. Similarly to EGF, the extracted TGF-alpha entirely displaced 125I EGF specifically bound to receptor. TGF-alpha produced by the A431/1522 cells also stimulated autophosphorylation of the EGF receptor. PMID- 8361492 TI - [Electron-microscopic study of the morphology of scaffold-like structures in chromosomes, formed by formamide]. AB - Isolated human metaphase chromosomes treated with formamide and prepared for electron microscopy by protein monolayer technique have an appearance of loop shaped chromatin fibers coming off the central scaffold-like structures, such chromosomes having approximately the same histone content as those before treatment. The morphology of scaffold-like structures at different formamide concentrations is described. It is shown that during formamide treatment the protein-protein and/or protein-DNA interactions are weakened because of disruption of hydrogen bonds. However, the intermolecular interactions in the chromosomes allow them to preserve their shape and size. The changes in the structure of formamide-treated chromosomes become readily visible after spreading on the hypophase surface. It is shown that after removal of formamide from the incubation solution by dialysis, chromosomes condense drastically. The data obtained are in good agreement with the loop model of chromosome organization. However they evidence also that the scaffold in the form of a rigid characteristic chromosome structure arises as a result of redistribution and/or aggregation of chromosomal proteins during chromosome preparation. PMID- 8361493 TI - [Formation of various types of complexes upon the interaction of anthraquinones with DNA]. AB - The optical properties (circular and linear dichroism) of the 11 anthraquinone antibiotics complexed with DNA molecules under conditions giving rise to cholesteric liquid-crystalline dispersions were investigated. Complexes of compounds A911 and A912 with double-stranded linear or circular DNA molecules differ strongly in their properties from those of other anthraquinones. The possible reasons of these differences and their possible correlation with the biological activity of the A911 and A912 are discussed. PMID- 8361494 TI - [Immunoreactivity of synthetic peptides, corresponding to B-cellular epitopes of human type I T-lymphotrophic virus structural proteins]. AB - The immunoreactivity of 25 synthetic peptides corresponding to amino acid fragments of the HTLV-I structural proteins p19 gag, gp46 and gp21 env were studied in enzyme linked immunosorbent assay using a serum panel of 70 reference positive specimens with anti-HTLV-I antibodies. The location of the synthetic peptides containing the B-cell epitopes of HTLV-I was established. Anti-HTLV-I antibodies effectively recognized these peptides. The significance of some amino acids for forming the HTLV-I antigenic determinants was estimated. The synthetic peptides with amino acid sequences 100-130 p19 gag and 176-201 gp46 env were found to have most immunoreactivity (90-99% recognition by sera of HTLV-I infected patients) and mimic the immunodominant B-cell epitopes of HTLV-I structural proteins. PMID- 8361495 TI - [Loss of total 5-methylcytosine from the genome during cell culture aging coincides with the Hayflick limit]. AB - Analyzing the data about the age-related 5-methylcytosine (5mC) loss from DNA of cell cultures, the following conclusions have been made: 1. The rate of 5mC loss from DNA does not depend on the cell donor age; it remains constant during the logarithmic phase of cell growth, and may vary significantly in different cell lines. 2. The rate is inversely proportional to their Hayflick limit and to the species lifespan of cell donors. 3. In immortal cell lines the 5mC content in DNA is stable or increases with aging. 4. Hayflick limit estimations coincide with or are lower than the number of cell population doublings that corresponds to all 5mC loss from cell genome. A simple and fast method has been proposed for Hayflick limit prognostication by analysis of the rate of DNA hypomethylation. It may be used for early diagnosis of precrisis and immortal cell lines. Evidence has been obtained that age-dependent 5mC loss from DNA is the result of accumulating 5mC-->T+C substitutions that occur during DNA methylation in every cell division. The loss of all genomic 5mC residues during the lifespan may correspond to accumulation of about 3 x 10(6) 5mC-->T transitions or, on average, one mutation per gene. This may be one of the main reasons of the "catastrophe of errors" and cessation of cell proliferation. It is calculated that the rate of 5mC-->T transitions in normal cells may be 2.3 x 10(-5) per site in each cell doubling in human, 6 x 10(-5) in hamster, and 4.6 x 10(-4) in mouse. DNA methylation as a generator of mutations may be a "counter" of cell divisions and thus be one of the molecular mechanisms of the Hayflick phenomenon. The conclusion is made that the DNA methylation system may be considered as a genetically programmed mechanism for accumulating mutations during cell aging. PMID- 8361496 TI - [Characteristics of the pH2-42 probe for the D13S25 locus of human chromosome 13: nucleotide sequence, localization, and PCR markers]. AB - The sequence of the HindIII-HindIII fragment of probe pH2-42 of locus D13S25 of human genome is given. Localization of the probe in q14-q21 of human chromosome 13 is confirmed by hybridization in situ. Seven oligonucleotide primers for the polymerase chain reaction are chosen so that amplified products almost completely cover the analyzed sequence. Reconstruction of localization of polymorphic SspI sites in D13S25 was based on the data of Bowcock and Hebert [3] and this study. The results obtained make it possible to use the primer sets to screen cosmid libraries and to mark the D13S25 locus of human chromosome 13. PMID- 8361497 TI - [Formation and properties of S-protein complexes with S-peptide-containing hybrid polypeptides]. AB - The fused polypeptides of human epidermal growth factor and one or two S-peptide of RNase A was shown to form stoichiometric (1:1) strong noncovalent and enzymatically active complexes with S-protein of RNase A. The dissociation constants for these complexes were found to be 5.0 x 10(-7) M and 1.1 x 10(-7) M. The complexes of polypeptides with S-protein were capable to hydrolyze ribopolynucleotides, and pyrimidine-2',3'-cyclophosphates specifically, like RNase S'. A possibility was shown of effective purification of the S-peptide containing polypeptides by affinity chromatography in which S-protein is immobilized on solid supports. PMID- 8361498 TI - [Functioning and silent regrouped immunoglobulin genes in the hybridoma genome]. AB - Rearranged genes for heavy and light immunoglobulin chains have been studied in the genomes of hybridoma PTF-02 and parent myeloma P3-X63.Ag8.653. The hybridoma was shown to contain three rearranged allelic variants of the heavy chain gene's locus. Gene H2, responsible for the synthesis of the heavy chain of the antibody to transferrin, was transmitted to the hybridoma cell from a lymphocyte. The structure of the 5'-terminal codons of this gene corresponds to N-terminal amino acid residues of a heavy chain expressed by PTF-02 hybridoma. Two other genes (H1 and H3) were found both in the hybridoma and parent myeloma. Both H1 and H3 genes have serious defects in their structure and do not function. Rearranged k-genes were also identified both in the hybridoma and parent myeloma. A functional (K2) gene appeared in the hybridoma genome from an antigen-stimulated lymphocyte. The fetal mouse Vk gene, which has high homology (96.5%) with the K2 gene, was cloned and sequenced. Both K2 and the Vk fetal gene belong to one subfamily of k-genes. The rearranged gene K1 is nonfunctional because it has lost the Jk locus. This gene was transmitted from myeloma used for fusion. In such a way, the origin of all rearranged heavy and light chain genes in hybridoma PTF-02 was established. PMID- 8361499 TI - [Model of the spatial structure of peptide T]. AB - The spatial structure model of peptide T (AIDS reproduction inhibitor, the amino acid sequence of which corresponds to the fragment into the binding site of the virus protein gp120 with T4 receptor) is proposed. Peptide structure modelling has been carried out by the previously developed method based on joint usage of the molecular mechanics algorithms and NMR spectroscopy data. To build the model, two-dimensional nuclear Overhauser effect spectroscopy data for RNase A homologous fragment 22-26 were taken from the literature. The result of the presented work was a set consisting of six types of low-energy structures with different spatial packing of the peptide main chain. All structural types have been shown to be characterized by the lack of strict determination of the side chain conformations of the amino acid residues that can be realized in a few states providing approximately equal (within the given type) stabilization of one main chain form. At the same time, despite the definite differences, all of the selected structures were characterized by the presence of two consecutive reverse polypeptide chain turns at the C-terminal pentapeptide fragment. This site is supposed to be responsible for the peptide binding with T4 receptor and the antiviral effect. PMID- 8361500 TI - [Creation of a hybrid protein gene based on Bacillus thuringiensis delta endotoxins CryIIIA and CrIA(a) and expression of its derivatives in Escherichia coli]. AB - The 5'-terminal fragment (containing 1-565th codons) of Bacillus thuringiensis var. tenebrionis gene for the Coleoptera-specific delta-endotoxin CryIIIA was cloned. This sequence was extended with either only a homologous fragment of CryIA(a) or that one together with in-frame NPTII or GUS coding sequences. The obtained gene derivatives were expressed in E. coli. The analysis of hybrid polypeptides confirmed the enzymatic activities of bifunctional proteins and showed toxic properties of "insectotoxin-NPTII" against Colorado potato beetle (Leptinotarsa decemlineata). PMID- 8361501 TI - An element of the transforming growth factor-beta 1 5'-untranslated region represses translation and specifically binds a cytosolic factor. AB - In many cell types, there is a discrepancy between transforming growth factor beta 1 (TGF-beta 1) mRNA and TGF-beta 1 protein, suggesting that expression of TGF-beta 1 is regulated posttranscriptionally. We have previously shown that a 137-nucleotide (nt) region of the TGF-beta 1 5'-untranslated region (UTR) potently inhibits the expression of a heterologous reporter gene, suggesting a role for this region in the posttranscriptional inhibition of TGF-beta 1 expression. To study the mechanism of inhibition, a chimeric plasmid containing this region of the TGF-beta 1 5'-UTR and the reading frame of the human GH gene was stably transfected into C2C12 myoblastic cells. Our results show that the TGF beta 1 5'-UTR inhibits GH expression by inhibiting GH mRNA translation. In vitro gel retardation and cross-linking assays using a radiolabelled RNA probe transcribed from this region of the TGF-beta 1 5'-UTR demonstrate the specific binding of a cytosolic factor. Deletion of a potential stem-loop-forming region abolishes binding of this factor and partially restores GH production. These results suggest that posttranscriptional inhibition of TGF-beta 1 expression is at the level of mRNA translation and that a cytosolic factor may regulate TGF beta 1 mRNA translation. PMID- 8361502 TI - A naturally occurring growth hormone receptor mutation: in vivo and in vitro evidence for the functional importance of the WS motif common to all members of the cytokine receptor superfamily. AB - To obtain an animal model for studying the role of the GH receptor (GHR) in growth and development, we analyzed a sex-linked dwarf (SLD) chicken strain (Leghorn) which exhibits phenotype similarities with a human genetic growth disorder, an autosomal recessive GH resistance condition (Laron dwarfism). Having previously demonstrated the responsibility of the human GHR gene in the Laron phenotype, we focused our analysis on the corresponding gene in SLD chickens. Sequencing of the whole coding region of the chicken GHR cDNA identified a G-to-T transversion segregating with the SLD phenotype and generating an isoleucine instead of a serine at position 199 within a highly conserved region close to the junction between the extracellular and transmembrane domains. This defect involves the last invariant amino acid of the WS-like motif (amino acid sequence WSXWS) common to all members of the cytokine receptor superfamily. Transfection of a mutated GHR cDNA containing this mutation into eukaryotic cells led to the synthesis of a receptor protein that displayed impaired plasma membrane expression and binding activity. These data define the molecular basis for the SLD phenotype and identify this strain as an interesting model for studying Laron dwarfism in humans; this animal model may also represent a system in which therapeutic strategies to promote growth can be evaluated. Finally, the nature of the molecular defect identified provides direct evidence for the functional importance of the WS motif in GHRs and related receptors. PMID- 8361503 TI - The risk of childhood cancer after neonatal exposure to vitamin K. AB - BACKGROUND: Two recent studies have found that infants who received intramuscular vitamin K were at twice the expected risk for cancer during childhood. Since nearly all newborns in the United States receive this drug, the public health implications of this association, if confirmed, would be substantial. METHODS: We examined the relation between vitamin K and cancer in a nested case-control study that used data from the Collaborative Perinatal Project, a multi-center, prospective study of pregnancy, delivery, and childhood. Among 54,795 children born from 1959 through 1966, 48 cases of cancer were diagnosed after the first day of life and before the eighth birthday. Each case child was matched with five randomly selected controls whose last study visit occurred at or after the age when the case child's cancer was diagnosed. Exposure to vitamin K was determined from study forms and medical records. RESULTS: Vitamin K had been administered to 68 percent of the 44 case children and 71 percent of the 226 controls for whom data were available (matched odds ratio, 0.84; 95 percent confidence interval, 0.41 to 1.71). The odds ratio was 0.47 (95 percent confidence interval, 0.14 to 1.55) for leukemia and 1.08 (95 percent confidence interval, 0.45 to 2.61) for other cancers. Sequential adjustment for potential confounding factors did not change the results substantially. CONCLUSIONS: We found no association between exposure to vitamin K and an increased risk of any childhood cancer or of all childhood cancers combined, although a slightly increased risk could not be ruled out. The benefits of neonatal vitamin K prophylaxis against hemorrhagic disease have been well described. Unless other evidence supporting an association between vitamin K and cancer appears, there is no reason to abandon the routine administration of vitamin K to newborns. PMID- 8361504 TI - Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. AB - BACKGROUND: Translocations involving chromosome band 11q23 are very frequent in both acute lymphoblastic and acute myeloid leukemias and are the most common genetic alteration in infants with leukemia. In all age groups and all phenotypes of leukemia, an 11q23 translocation carries a poor prognosis. A major question has been whether one or several genes on band 11q23 are implicated in these leukemias. Previously, we identified the chromosomal breakpoint region in leukemias with the common 11q23 translocations and subsequently cloned a gene named MLL that spans the 11q23 breakpoint. METHODS: We isolated a 0.74-kb BamHI fragment from a complementary DAN (cDNA) clone of the MLL gene. To determine the incidence of MLL rearrangements in patients with 11q23 abnormalities, we analyzed DNA from 61 patients with acute leukemia, 3 cell lines derived from such patients, and 20 patients with non-Hodgkin's lymphoma and 11q23 aberrations. RESULTS: The 0.74-kb cDNA probe detected DNA rearrangements in the MLL gene in 58 of the patients with leukemia, in the 3 cell lines, and in 3 of the patients with lymphoma. All the breaks occurred in an 8.3-kb breakpoint cluster region within the MLL gene. The probe identified DNA rearrangements in all 48 patients with the five common 11q23 translocations involving chromosomes 4, 6, 9, and 19, as well as in 16 patients with uncommon 11q23 aberrations. Twenty-one different chromosomal breakpoints involving the MLL gene were detected. CONCLUSIONS: MLL gene rearrangements were detected with a single probe and a single restriction enzyme digest in all DNA samples from patients with the common 11q23 translocations as well as in 16 patients or cell lines with other 11q23 anomalies. The ability to detect an MLL gene rearrangement rapidly and reliably, especially in patients with limited material for cytogenetic analysis, should make it possible to identify patients who have a poor prognosis and therefore require aggressive chemotherapy or marrow transplantation. PMID- 8361505 TI - Analysis of dystrophin expression after activation of myogenesis in amniocytes, chorionic-villus cells, and fibroblasts. A new method for diagnosing Duchenne's muscular dystrophy. AB - BACKGROUND: DNA analysis of peripheral-blood leukocytes is routinely used to demonstrate mutations in the dystrophin gene in patients with Duchenne's or Becker's muscular dystrophy. In approximately 35 percent of patients, DNA studies are not informative; in these patients immunochemical analysis of a muscle-biopsy specimen can determine whether dystrophin, the protein product of the gene for Duchenne's dystrophy, is present at reduced levels or absent. DNA analysis can be performed in amniocytes or chorionic-villus cells to identify mutations of the dystrophic gene prenatally, but immunochemical testing for dystrophin cannot be performed because the protein is not expressed in these cells. METHODS: To circumvent this limitation in prenatal diagnosis, we induced myogenesis in 21 cultures of skin fibroblasts, 49 amniocyte cultures, and 6 chorionic-villus cell cultures by infecting the cells with a retrovirus vector containing MyoD, a gene regulating myogenesis. Transfection of MyoD into cells that do not normally develop into muscle cells results in the production of a protein that switches on myogenesis. We performed immunocytochemical analysis for dystrophin in the MyoD converted muscle cells. RESULTS: We found that 60 of 61 myotube cultures from subjects with no family history of Duchenne's dystrophy expressed dystrophin. Both myotube cultures from the two patients with Becker's dystrophy also expressed dystrophin, but all cultures from nine patients and two fetuses with Duchenne's dystrophy were dystrophin-deficient. CONCLUSIONS: Immunocytochemical analysis of dystrophin in genetically altered non-muscle cells is feasible and may be applicable to the prenatal and postnatal diagnosis of Duchenne's muscular dystrophy when conventional DNA analysis is not informative. PMID- 8361506 TI - Brief report: deletion of the dystrophin muscle-promoter region associated with X linked dilated cardiomyopathy. PMID- 8361507 TI - Images in clinical medicine. Paradoxical Embolus. PMID- 8361508 TI - Possible influence of the prospective payment system on the assignment of discharge diagnoses for coronary heart disease. AB - BACKGROUND: The prospective payment system, under which diagnosis-related groups (DRGs) are used to reimburse hospitals for the care of Medicare patients, replaced the fee-for-service method of payment in Rhode Island in 1983 and in Massachusetts in 1985. Changes in financial incentives resulting from the use of the DRG system may have influenced the assignment of discharge diagnostic codes away from those with lower reimbursement toward codes with higher reimbursement. METHODS: We collected data from the hospital records of patients 35 through 74 years of age who were discharged with codes 410 through 414 (representing various categories of coronary heart disease) of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The patients were discharged from seven hospitals in two New England communities (one in Rhode Island and one in Massachusetts) between 1980 and 1988. The rates of diagnosis of various forms of coronary heart disease were determined by studying ICD-9-CM hospital discharge codes (codes 410 and 411 for acute forms of coronary heart disease and codes 412, 413, and 414 for chronic forms) and by using a computerized diagnostic algorithm designed to detect definite myocardial infarction and fatal coronary heart disease. RESULTS: The rates of definite coronary events diagnosed by the algorithm and by the study of ICD-9-CM codes 410 through 414 were constant or increased slightly during the study period. However, the frequency of assignment of codes for the acute forms of coronary heart disease (which entail higher reimbursement) rose from 35.2 percent to 48.4 percent among discharged patients with cardiac disease after the institution of DRGs. The majority of this increase was associated with the code for unstable angina pectoris. The frequency of assignment of codes for the chronic forms of coronary heart disease (which entail lower reimbursement) decreased reciprocally, from 64.8 percent to 51.6 percent (P < 0.001). CONCLUSIONS: Our data are consistent with the hypothesis that the prospective reimbursement system has influenced the assignment of hospital discharge codes in a way that would increase payment to hospitals. However, the data do not permit us to distinguish whether hospitals began to assign more precise diagnoses with the advent of the DRG system, or whether they began to favor diagnoses of acute conditions solely for financial reasons. PMID- 8361509 TI - Tick-borne diseases in the United States. PMID- 8361510 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 38-1993. Renal failure and a painful toe in a 70-year-old man after an acute myocardial infarct. PMID- 8361511 TI - Vitamin K and the newborn. PMID- 8361512 TI - Progress in defining the causes of idiopathic dilated cardiomyopathy. PMID- 8361513 TI - Unraveling the fat embolism syndrome. PMID- 8361514 TI - Health care in Canada and the United States. PMID- 8361515 TI - Health care in Canada and the United States. PMID- 8361516 TI - Health care in Canada and the United States. PMID- 8361517 TI - Attention deficit-hyperactivity disorder. PMID- 8361518 TI - Attention Deficit-hyperactivity disorder. PMID- 8361519 TI - Management of chronic obstructive pulmonary disease. PMID- 8361520 TI - Management of chronic obstructive pulmonary disease. PMID- 8361521 TI - Management of chronic obstructive pulmonary disease. PMID- 8361522 TI - Treatment of neurocardiogenic syncope. PMID- 8361523 TI - Treatment of neurocardiogenic syncope. PMID- 8361524 TI - Treatment of neurocardiogenic syncope. PMID- 8361525 TI - 14-year follow-up of central embolization by a guide wire. PMID- 8361526 TI - Potentiometric stripping analysis of selected heavy metals in biological materials. AB - Different biological materials such as edible oils, refined and unrefined cane and beet sugar and tea (black and green) leaves were assayed for the heavy metals cadmium, copper, lead and zinc. The results revealed significant differences in heavy metal contents within each class of the biological materials (P < 0.05). Cadmium was not detectable in sugar samples. Among the oils, highest amounts of copper (0.263 microgram/g) and lead (0.154 microgram/g) were in corn oil and zinc in olive oil (3.01 micrograms/g) whereas cadmium exhibited a narrow range (0.023 0.033 microgram/g). The samples of beet-sugar generally contained higher levels of the heavy metals than cane-sugar. Black and green tea leaves contained 0.411 0.908 microgram Cd/g, 6.500-9.220 micrograms Cu/g, 2.200-5.238 micrograms Pb/g, and 14.500-25.180 micrograms Zn/g. PMID- 8361527 TI - Oral intake of cadmium, cobalt, copper, iron, lead, nickel, manganese and zinc in the university student's diet. AB - A duplicate diet meal study was carried out with a group of university students living in a hostel, in order to estimate the intake of Zn, Cd, Co, Cu, Fe, Mn, Ni and Pb. Zn, Cu, Fe, Mn and Ni were determined by flame atomic absorption spectrophotometry and Cd, Co and Pb by graphite furnace atomic absorption spectrophotometry after a nitric acid wet digestion procedure. The estimated intake values from the contents of breakfast, lunch, dinner and drinks were compared with the values of the Provisional Tolerable Daily Intake (PTDI) in the case of Cd and Pb, Recommended Dietary Allowances (RDA) of Co, Fe and Zn and Estimated Safe and Adequate Dietetic Daily Intake (ESADDI) of Cu and Mn. Neither excessive intake of Pb and Cd nor deficiencies in Zn, Co, Fe, Mn or Ni were observed, but Cu intake was lower than the ESADDI. PMID- 8361528 TI - Role of vasoactive intestinal polypeptide (VIP), secretin and gastrin in the genesis of the late exocrine pancreatic hypersecretion, food intake dependent in conscious dogs. AB - Plasma levels of vasoactive intestinal polypeptide (VIP), secretin and gastrin were studied in four saphenous vein-catheterized dogs during the first 12 h after ingestion of a standard solid meal. Under these conditions we found significant postprandial increases in secretion only, which rose from a basal value of 219 +/ 27 pg/ml to 449 +/- 66 pg/ml 60 min postprandial (p < 0.001), and remained elevated until 4 h after food intake. However, no increase was seen from 8 to 12 h in any of the hormones studied, indicating that they are not directly involved in the enhancement of exocrine pancreatic secretion during this period. PMID- 8361529 TI - RNA splicing. Question of commitment. PMID- 8361530 TI - Contraception. Towards healthier infertility. PMID- 8361531 TI - Tumour suppressor genes. No room at the p53 inn. PMID- 8361532 TI - Cell checkpoint and radiosensitivity. PMID- 8361533 TI - Disruption of the CNTF gene results in motor neuron degeneration. AB - CNTF is a cytosolic molecule expressed postnatally in myelinating Schwann cells and in a subpopulation of astrocytes. Although CNTF administration prevents lesion-mediated and genetically determined motor neuron degeneration, its physiological function remained elusive. Here it is reported that abolition of CNTF gene expression by homologous recombination results in a progressive atrophy and loss of motor neurons in adult mice, which is functionally reflected by a small but significant reduction in muscle strength. PMID- 8361534 TI - UK scientists test liposome gene therapy technique. PMID- 8361535 TI - Backlash threatens biomedicine. PMID- 8361536 TI - Inverse-dynamics model eye movement control by Purkinje cells in the cerebellum. AB - Many lines of evidence suggest that the cerebellum is involved in motor control. But what features of these movements are encoded by cerebellar neurons? For slow tracking eye movements, the activity of Purkinje cells in the ventral paraflocculus of the cerebellum is known to be correlated with eye velocity and acceleration. Here we show that the complex temporal pattern of the firing frequency that occurs during the ocular following response elicited by movements of a large visual scene can be reconstructed by an inverse-dynamics representation, which uses the position, velocity and acceleration of eye movements. Further analysis reveals that the velocity and acceleration components can provide appropriate dynamic drive signals to ocular motor neurons, whereas the position component often has the wrong polarity. We conclude that these Purkinje cells primarily contribute dynamic command signals. PMID- 8361538 TI - Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition. AB - The vertebrate skeleton is formed primarily by endochondral ossification, starting during embryogenesis when cartilage anlagens develop central regions of hypertrophic cartilage which are replaced by bony trabeculae and bone marrow. During this process chondrocytes express a unique matrix molecule, type X collagen. We report here that mice carrying a mutated collagen X transgene develop skeletal deformities including compression of hypertrophic growth plate cartilage and a decrease in newly formed bone, as well as leukocyte deficiency in bone marrow, reduction in size of thymus and spleen, and lymphopenia. The defects indicate that collagen X is required for normal skeletal morphogenesis and suggest that mutations in COL10A1 are responsible for certain human chondrodysplasias, such as spondylometaphyseal dysplasias and metaphyseal chondrodysplasias. PMID- 8361537 TI - Different roles of alpha beta and gamma delta T cells in immunity against an intracellular bacterial pathogen. AB - Several bacterial pathogens of medical importance are able to persist and replicate inside host mononuclear phagocytes. Protective immunity depends on specific T lymphocytes that induce granulomatous lesions at the sites of bacterial multiplication. Listeria monocytogenes is an intracellular pathogen that replicates inside mononuclear phagocytes and hepatocytes of mice. Invasion from the phagosomal compartment into the cytoplasmic compartment is the principal mechanism of intracellular survival. Early in infection, resistance against L. monocytogenes is mediated by polymorphonuclear phagocytes which destroy infected liver cells, followed by natural killer cells which activate macrophages by means of interferon-gamma (refs 6, 7). A specific immune response by T cells then develops which leads to sterile eradication of the microbes. T cells are also responsible for the highly effective protection in vaccinated mice against secondary infections. Although the role of alpha beta T cells has been demonstrated in these immune responses, that of gamma delta T cells is unclear. Here we use mice that selectively lack either alpha beta or gamma delta T cells as a result of targeted germ-line mutations in their T-cell receptor genes to investigate the relative roles of these T-cell populations during experimental infection with L. monocytogenes. We find that in primary listeriosis, either alpha beta or gamma delta T cells are sufficient for early protection. Resistance to secondary infection is mediated mainly by alpha beta T cells but also involves gamma delta T cells. Thus alpha beta T-cell-deficient mice can be rendered partially resistant by vaccination, and gamma delta T cells are shown to be responsible for this protective effect. In infected gamma delta T-cell-deficient mice we noticed the appearance of unusual liver lesions, indicating that gamma delta T cells have a unique regulatory role in this bacterial infection. PMID- 8361539 TI - Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. AB - The microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospholipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent M(r) of 88K (refs 1-3). It is isolated as a soluble protein from the lumen of the microsomal fraction of liver and intestine. The large subunit of MTP was not detectable in four unrelated subjects with abetalipoproteinaemia, a rare autosomal recessive disease characterized by a defect in the assembly or secretion of plasma lipoproteins that contain apolipoprotein B (ref. 6). We report here the isolation and sequencing of complementary DNA encoding the large subunit of MTP. A comparison of this sequence to corresponding genomic sequences from two abetalipoproteinaemic subjects revealed a homozygous frameshift mutation in one subject and a homozygous nonsense mutation in the other. The results indicate that a defect in the gene for the large subunit of MTP is the proximal cause of abetalipoproteinaemia in these two subjects, and that MTP is required for the secretion of plasma lipoproteins that contain apolipoprotein B. PMID- 8361540 TI - Presynaptic A-current based on heteromultimeric K+ channels detected in vivo. AB - A wide variety of voltage-gated K+ channels are involved in the regulation of neuronal excitability and synaptic transmission. Their heterogeneity arises in part from the large number of genes encoding different K+ channel subunits (reviewed in ref. 1). In addition, heterologous expression studies indicate that assembly of distinct subunits into heteromultimeric channels may contribute further to K+ channel diversity. A question has been whether heteromeric K+ channels actually form in vivo, and if so, whether specific combinations of subunits could account for major K+ currents identified in neurons. We present here biochemical evidence that Kv1.4 and Kv1.2, two K+ channel subunits of the Shaker subfamily, co-assemble in rat brain. The Kv1.4/Kv1.2 heteromultimer combines features of both parent subunits, resulting in an A-type K+ channel. Immunocytochemical evidence suggests that the heteromultimers are localized in axons and nerve terminals. We propose that Kv1.4/Kv1.2 heteromultimers may form the molecular basis of a presynaptic A-type K+ channel involved in the regulation of neurotransmitter release. PMID- 8361541 TI - Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons. AB - Voltage-gated potassium (K+) channels display a wide variety of conductances and gating properties in vivo. This diversity can be attributed not only to the presence of many K(+)-channel gene products, but also to the possibility that different K(+)-channel subunits co-assemble to form heteromultimeric channels in vivo. When expressed in Xenopus oocytes or transfected cells, K(+)-channel polypeptides assemble to form tetramers. Certain combinations of Shaker-like subunits have been shown to co-assemble, forming heteromultimeric channels with distinct properties. It is not known, however, whether K(+)-channel polypeptides form heteromultimeric channels in vivo. Here we describe the co-localization of two Shaker-like voltage-gated K(+)-channel proteins, mKv1.1 and mKv1.2, in the juxtaparanodal regions of nodes of Ranvier in myelinated axons, and in terminal fields of basket cells in mouse cerebellum. We also show that mKv1.1 and mKv1.2 can be coimmunoprecipitated with specific antibodies that recognize only one of them. These data indicate that the two polypeptides occur in subcellular regions where rapid membrane repolarization may be important and that they form heteromultimeric channels in vivo. PMID- 8361542 TI - Inhibition of DNA replication factor RPA by p53. AB - The tumour suppressor p53 specifically interferes with the onset of S phase. The mechanism of the growth suppression action of the protein is unclear, though recent evidence points to transcriptional activation and repression functions of the protein. A competing hypothesis suggests that p53 interacts with the DNA replication apparatus and directly interferes with DNA replication. The major evidence for this hypothesis is that p53 interacts with the simian virus 40 (SV40)-encoded protein T antigen and interferes with the ability of T antigen to unwind the SV40 origin of DNA replication, and recruit DNA polymerase alpha to the replication initiation complex. Here we report that p53 physically interacts with and inhibits the function of a cellular DNA replication factor, the single stranded DNA-binding protein complex RPA. PMID- 8361543 TI - Continuing confusion. PMID- 8361544 TI - Continuing confusion. PMID- 8361545 TI - Gaining time. PMID- 8361546 TI - Specific commitment of different pre-mRNAs to splicing by single SR proteins. AB - Higher eukaryotic cells express a family of essential splicing factors with a characteristic RNA-binding domain and serine/arginine-rich (SR) motif. These SR proteins, which include SC35 and SF2/ASF, are conserved from Drosophila to man, are required for early steps of spliceosome assembly and can influence splice site selections. To address their mechanisms of action, SR proteins were examined for their role in committing pre-messenger RNA to the splicing pathway. I report here that SC35 was sufficient on its own to form a committed complex with human beta-globin pre-mRNA. Examination of other SR proteins and pre-mRNA substrates revealed that single SR proteins committed different pre-mRNAs to splicing with pronounced substrate specificity. These results suggest that splicing of different pre-mRNAs may require distinct sets of SR proteins, and that the commitment by SR proteins may be a critical step at which alternative and tissue specific splicing is regulated. PMID- 8361547 TI - Non-injection methods for the production of embryonic stem cell-embryo chimaeras. AB - The simple aggregation of pluripotent ES cells with morulae-stage embryos can result in viable chimaeras at a similar frequency to that of blastocyst injection. The savings in time and equipment inherent in the aggregation techniques, however, make this approach well worth considering. PMID- 8361549 TI - Multiple inhibitory mechanisms mediate non-adrenergic non-cholinergic relaxation in the circular muscle of the guinea-pig colon. AB - The mechanisms responsible for nerve-mediated, non-adrenergic, non-cholinergic (NANC) relaxation in mucosa-free circular muscle strips from the proximal colon of the guinea-pig were investigated. Electrical field stimulation (EFS, 1-20 Hz, trains of 5 s duration, 100 V, 0.25 ms pulse width) in the presence of atropine (1 mumol/l) and guanethidine (3 mumol/l) evoked a triphasic motor response consisting of: (a) a primary relaxation, (b) a rebound contraction and (c) a secondary relaxation. These three responses were abolished by tetrodotoxin (1 mumol/l). B oth apamin (0.01-0.3 mumol/l), a known blocker of low conductance, calcium-activated potassium channels in smooth muscles, and L-nitro-arginine (L NOARG) (1-100 mumol/l), a known blocker of nitric oxide (NO) synthase, increased the tone of the strips. Maximum effects on tone were observed with 0.1 mumol/l apamin (21 +/- 3% of KCl-induced contraction) and 30 mumol/l L-NOARG (26 +/- 4% of KCl response). The combined administration of 0.1 mumol/l apamin and 30 mumol/l L-NOARG produced an increase in tone (47 +/- 5% of KCl response) that was larger than that produced by either compound alone. Neither apamin (0.1 mumol/l) nor L-NOARG (30 mumol/l) affected the isoprenaline-induced relaxation. Apamin (0.1 mumol/l) depressed, but did not abolish, the primary relaxation to EFS at all frequencies without affecting the secondary relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361548 TI - Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. AB - The regional distribution and the pharmacology of the binding sites labelled with the novel 5-hydroxytryptamine (serotonin) 5-HT1B/1D selective radioligand serotonin-O-carboxy-methyl-glycyl-[125I]tyrosinamide (abbreviated [125I]GTI for the sake of simplicity) was determined using quantitative autoradiography in rat brain. The distribution of [125I]GTI binding sites was largely comparable to that of [125I]iodocyanopindolol ([125I] ICYP) which labels 5-HT1B binding sites (in the presence of 8-OH-DPAT (8-hydroxy-[2N-dipropylamino]tetralin) and isoprenaline, to prevent binding to 5-HT1A and beta-adrenoceptor binding sites), although a detailed analysis revealed differences. The pharmacology of the [125I]GTI binding sites was analysed using compounds known to display high affinity for and/or distinguish between 5-HT1B and 5-HT1D sites: 5 carboxamidotryptamine (5-CT), sumatriptan, CP 93129 (5-hydroxy-3(4-1,2,5,6 tetrahydropyridyl)-4-azaindole), (-)pindolol, PAPP (4[2-[4-[3 (trifluoromethyl)phenyl]-1- piperazinyl]ethyl]benzeneamine), rauwolscine, and 8 OH-DPAT. The displacement of [125I]GTI by 5-CT was monophasic. By contrast, the selective 5-HT1B compound CP 93129 and (-)pindolol produced biphasic curves showing a majority of high affinity sites in the globus pallidus and the substantia nigra, whereas PAPP and sumatriptan (which are somewhat 5-HT1D selective) produced biphasic curves indicating a minority of high affinity sites in these areas. In addition, by blocking the 5-HT1B sites with 100 nM CP 93129, the remaining population of [125I]GTI binding sites could be studied and was found to have high affinity for PAPP, rauwolscine and 8-OH-DPAT. The pharmacological profile of the major binding component was typical of the 5-HT1B type: 5-CT > CP 93129 > or = (-)pindolol > sumatriptan > or = PAPP > rauwolscine. The profile of the minor component of [125I]GTI binding is best characterised as that of a 5-HT1D site: 5-CT > PAPP > or = sumatriptan > rauwolscine > (-)pindolol > or = CP 93129. The localisation of the non 5-HT1B [125I]GTI binding sites was characterised by blocking the 5-HT1B receptors with 100 nM CP 93129. Low densities of the 5-HT1D recognition sites were found to be present in globus pallidus, ventral pallidum, caudate-putamen, subthalamic nucleus, entopeduncular nucleus, substantia nigra (reticular part), nuclei of the (normal and accessory) optic tract, different nuclei of the geniculate body and frontoparietal cortex, although higher densities of 5-HT1B sites were always observed in the same structures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8361551 TI - N-acetyl-L-cysteine protects endothelial cells but not L929 tumor cells from tumor necrosis factor-alpha-mediated cytotoxicity. AB - The effect of N-acetyl-L-cysteine on the cytotoxicity of tumor necrosis factor alpha was investigated in cultured bovine pulmonary artery endothelial cells and L929 mouse tumor cells. In endothelial cells, a 72-h incubation with tumor necrosis factor-alpha (100 ng/ml) reduced the number of viable cells to 27% of control. Simultaneous incubation with N-acetyl-L-cysteine (0.5-5 mmol/l) protected endothelial cells from tumor necrosis factor-alpha-mediated cytotoxicity and increased viability in a concentration-dependent fashion to 69% of control. Under the same conditions, a 72-h incubation with tumor necrosis factor-alpha (100 ng/ml) reduced the number of viable L929 tumor cells to 31% of control. However, this cytotoxic response remained unaltered in the presence of N acetyl-L-cysteine (0.5-5 mmol/l). Similar results were obtained when using a lower concentration of tumor necrosis factor-alpha (50 ng/ml). These findings demonstrate protection from tumor necrosis factor-alpha-mediated toxicity by N acetyl-L-cysteine in endothelial cells but not in a tumor cell line. It is concluded that N-acetyl-L-cysteine might serve as a therapeutic agent to limit the vascular toxicity of tumor necrosis factor-alpha without affecting its antineoplastic activity. PMID- 8361550 TI - Morphine-induced hyperactivity in rats--a rebound effect? AB - The behavioural nature of the delayed hyperactivity induced by systemic administration of morphine was studied in rats. Different components of motility induced by morphine with or without naloxone or haloperidol at different times were analyzed by observation and quantified by an Opto-Varimex-3 Activity Meter. By this automatic recording system motility was discriminated into horizontal and two different vertical components and the total distance run by each of the rats was quantified by a computer program. Simultaneously the running pattern was recorded by a XY-plotter. By means of these recordings, three subsequent phases of behaviour could be recorded after morphine (15 mg/kg i.p.): 1. a depressed phase (akinesia) lasting 1.5-2 h, followed, 2. by an intermediate phase for 1-1.5 h, still dominated by akinesia but interrupted by sudden bursts of hyperactivity. Finally, 3. a hyperactivity phase lasted for 1.5-2 h, characterized by an equal enhancement of locomotor activity and stereotypy. After 30 mg/kg of morphine the hyperactivity was predominantly characterized by locomotor activity and stereotypy and rearing were less prominent than after the smaller dose. Naloxone (2 mg/kg i.p.) given at the beginning of the hyperactivity phase significantly antagonized rearing but not other motility parameters. However, coadministration of naloxone (2 mg/kg i.p.) simultaneously with morphine (15 mg/kg) clearly antagonized akinesia and completely prevented the development of the delayed hyperactivity. Haloperidol (0.2 mg/kg i.p.) at the beginning of the hyperactivity phase clearly antagonized all of the motility parameters seen during this phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361552 TI - [Acute myocardial infarct? Open the blood vessel involved]. PMID- 8361553 TI - [Immediate coronary angioplasty for acute myocardial infarct: indications on the move]. PMID- 8361554 TI - [Effect of clozapine in schizophrenia; starting points for current pharmacotherapeutics]. PMID- 8361555 TI - [Thrombolysis of leg arteries]. PMID- 8361556 TI - [Long-term prognosis following a myocardial infarct: clinically prognostic variables and cardiovascular risk factors]. AB - The long-term prognosis after myocardial infarction; clinical predictive variables and cardiovascular risk factors. In predicting long-term survival of 304 consecutive patients discharged after myocardial infarction between 1978 and 1981, and under 65 years of age, the significance of both hospital data and cardiovascular risk factors was examined. After discharge from hospital, the ten year all-cause total mortality was 35.5%. Sudden death accounted for 42% of the recorded causes of death. The patients were not yet treated with thrombolysis at that time. After multivariate analysis, age, previous myocardial infarction, abnormal chest X-ray (increased cardiothoracic ratio or pulmonary congestion) and an increased cholesterol level were found to be independent and significant predictors of the ten-year mortality. Hypertension and gender were not associated with mortality. Patients with a previous myocardial infarction had, after adjustment for differences in age and other variables, a relative risk of dying within ten years of 1.70 (95% confidence interval 1.05-2.75) compared with those with a first infarction. A gradual increase of the ten-year mortality with elevated serum cholesterol level could be demonstrated (relative risk 1.14 per mmol/l, 95% CI 1.01-1.28). In conclusion, several routinely obtained parameters after myocardial infarction were related to subsequent long-term survival. Of the prognostic factors that may lead to useful therapeutic intervention after myocardial infarction, hypercholesterolaemia was most clearly associated with a reduced survival in the present study. PMID- 8361557 TI - [Good results of endoscopic paranasal sinus surgery for chronic or recurrent sinusitis and for nasal polyps]. AB - Endoscopic sinus surgery is being applied increasingly for chronic or recurrent sinusitis and nasal polyps. We investigated the results, which we classified as subjective results (i.e. the opinion of the patient) and objective results (i.e. the result as seen with nasal endoscopy). The subjective result was 'good' in 85% of 92 patients with chronic or recurrent sinusitis, the objective result in 77% of the treated sides, with a median follow-up of 46 months. In 90 patients with nasal polyps the percentages were 90% and 65% respectively, with a follow-up of 24 months. In 63% of 30 patients with chronic obstructive lung disease and nasal polyps the pulmonary function increased postoperatively (FEV1). In 4.2% of 1235 operated sides in 593 patients local complications were seen. These were mainly minor complications. Only in 0.3% serious complications as a orbital hematoma or a CSF leak were seen. Endoscopic sinus surgery has good results and little morbidity. PMID- 8361558 TI - [Trends in incidence of sexually transmissible disorders in The Netherlands]. AB - In 1983 the Chief Medical Inspectorate set up a national registration of sexually transmitted diseases (STD), beside the system of statutorily notifiable diseases in the Netherlands. Data for this registration are collected by the nursing staff in STD clinics. Besides diagnosis and sex of the patient epidemiological background information is registered. The data show a decrease in the total number for gonorrhoea and syphilis in the period 1984-1990. Among homosexual men gonorrhoea increased after 1989. A decrease in STD was demonstrated among prostitute women. Further, the share of penicillinase producing Neisseria gonorrhoeae was found to be increasing in various subgroups, but not in homosexual men. Comparison of age, sex, prostitution, and sexual inclination of over 25,000 patients with Chlamydia trachomatis, gonorrhoea or syphilis infections indicate that syphilis was significantly more frequent among older patients and women than gonorrhoea, but less frequent among prostitutes. Syphilis patients were significantly more often visitors of prostitutes than patients with gonorrhoea, and were more often homosexual or bisexual. Chlamydiosis patients were mostly women and younger than gonorrhoea patients, they were less often working as a prostitute and less often homosexual or bisexual. PMID- 8361559 TI - [Sexual possibilities following total penis amputation]. AB - A male aged 45 was subjected to total penis amputation because of a penile carcinoma; a perineal urethral stoma was created. The postoperative course was uneventful. One month after the last operation the patient for the first time felt the need for sexual contact, but his wife hesitated. After medical sexological counselling, the partners achieved satisfactory sexual functioning with the husband occasionally having an orgasm. PMID- 8361560 TI - [Hearing disorders in nursing home patients is difficult to assess when relying on caregivers' and patients' judgment]. PMID- 8361561 TI - [Hearing disorders in nursing home patients are difficult to assess when relying on caregivers' and patients' judgment]. PMID- 8361562 TI - [Good results from treatment with 100% oxygen for acute carbon monoxide poisoning; for the moment no indication for hyperbaric oxygenation]. PMID- 8361563 TI - [Endometrial carcinoma during estrogen replacement therapy in spite of addition of progestagens]. PMID- 8361564 TI - [Parametrial coitus]. PMID- 8361565 TI - [Magnetic resonance spectroscopy in cerebral blood flow metabolism (series 8)]. PMID- 8361566 TI - [Molecular biological characteristics of brain tumor]. PMID- 8361567 TI - [Histological study of the outer membrane of chronic subdural hematoma: possible mechanism for expansion of hematoma cavity]. AB - Relationship between the histological features of the outer membrane of chronic subdural hematoma and computed tomography (CT) findings, and the period from trauma to surgery were studied, and the mechanism of hematoma enlargement was discussed. This study included 43 patients aged 16 to 84 years. The outer membranes collected during operation were examined by hematoxylin and eosin staining and elasticavan Gieson staining. Histological features were classified into 4 types according to maturity and intensity of the inflammatory reaction and hemorrhage. Type I: Noninflammatory membrane. This type of membrane was observed in 3 cases. This membrane, containing immature fibroblasts and collagen fibers, was associated with very slight or sparse cell infiltration and neocapillaries. Type II: Inflammatory membrane. This type of membrane was observed in 21 patients. The type, consisting of one layer of immature connective tissue, was associated with marked cell infiltration and vascularization throughout the entire thickness. Type III: Hemorrhagic-inflammatory membrane. This type of membrane was observed in 14 patients. This type had a structure of 2 or 3 layers, and was associated with capillaries with a large lumen on the side of the dura mater and marked cell infiltration and many thin new vessels on the side of the hematoma cavity. Some patients showed a layer consisting of only collagen fibers and fibroblasts between two such layers. In addition, hemorrhage into the membrane was often observed. Type IV: Scar-inflammatory membrane. This type of membrane was observed in 4 patients. This type showed inflammatory cell infiltration, neovascularization and hemorrhage in the outer membrane of cicatricial tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361569 TI - [Treatment and prognosis of spinal AVM]. AB - Spinal arteriovenous malformation (AVM) is a relatively rare disease. We assessed the results of treatment of spinal AVM in 17 patients. Our classification was based on the radiographic appearance in selective spinal angiograms. There were 3 cases of single coiled type AVM, 3 of juvenile type, 5 of glomus type, and 6 of so-called dural AVM. All three patients with single coiled type AVM underwent microsurgical resection of the AVM. All three with the juvenile type underwent artificial embolization. Both patients with glomus type and dural AVM were treated by either embolization and/or surgery. Magnetic resonance imaging and magnetic resonance angiography visualized the spinal AVM well, and were useful for diagnosis and post-treatment follow-up. PMID- 8361568 TI - [Nutritional assessment for patients with neurosurgical diseases]. AB - There have been few guidelines in the field of nutritional management with regard to neurosurgical patients. In this review, caloric intake and nutritional parameters were measured in 24 patients in the acute stage and 32 patients in the chronic stage (prolonged unconscious state). We ascertained (1) whether the caloric intake was adequate or not, (2) the relationship between the grade of neurological damage and the nutritional assessment, and (3) we discussed the relationship between diseases and the nutritional assessments. The acute-stage patients, 14 male and 13 female, consisted of both a neurologically good prognostic group and a neurologically poor prognostic group. All of the prolonged unconscious patients revealed poor prognosis. The nutritional assessment was referred to such parameters as, diet and nutrition, anthropometric measurements, laboratory tests, immunological parameters and prognostic nutritional index. The results were, 1) the acute stage patients received less caloric intake than their resting energy expenditure, 2) the neurologically poor prognostic patients showed muscle atrophy and decrease of creatinine-height index which represents muscle content, 3) there was no significant differences between the assessment parameters in each disease, and 4) serum electrolytes decreased in prolonged unconscious patients with a small amount of caloric intake. PMID- 8361570 TI - [Clinical problems in the management of aged patients with severe head injury: analysis of neurological findings and CT findings]. AB - Aged patients were defined as those of 65 years or more of age. Among 457 patients with severe head injury [Glasgow Coma Scale score (GCS) of 8 or less], sixty-five aged patients (14%) were analyzed with special reference to their pretreatment neurological status, CT findings and outcome in comparison with 141 (31%) of those from 40 to 64 years of age. As a cause of injury, the incidence of traffic accidents and falls and tumbles did not differ statistically in both groups. Neither did the severity (GCS score) significantly differ in the two groups. Three important neurological findings [pupillary abnormality, impaired or absent oculocephalic reflex and poor motor response (GCS motor score < or = 3)], were analyzed as the prognostic factors. Poor motor response was the sole finding that was significantly more frequent in the aged. On CT in the aged, acute subdural hematoma was most common among the extraparenchymal hematoma. Hemorrhagic lesions were the more common parenchymal lesions. On the other hand, diffuse cerebral swelling was rare in the aged. The outcome was significantly poor in the aged; only 6% had good outcome (good recovery and moderate disability), and 80% died. In conclusion, these results suggested that the poor outcome was due to severe primary brain damage added to poor brain plasticity in the aged. PMID- 8361571 TI - [Arteriovenous malformation resembling galenic aneurysm]. AB - A girl who had just turned one year old was transported to our hospital because of an episode of general convulsive seizure. Neurological examinations demonstrated a comatose consciousness level, moderate right hemiparesis and conjugate deviation to the right. CT scan on admission revealed an intracerebral hematoma in the left medial temporal lobe associated with intraventricular hemorrhage in the lateral and third ventricles. MRI also showed the hematoma with evidence of a dilated venous system. Angiography demonstrated a huge venous sac fed by the left posterior choroidal artery and left anterior choroidal artery drained ultimately into the remnant of the tentorial sinus. Firstly, two courses of transfemoral embolization using platinum micro-coils were performed. Initially, the posterior choroidal artery and a branch of the anterior choroidal artery were occluded successfully. Then, two branches from the posterior cerebral artery were occluded one week after the initial procedure. She underwent the operation via the left subtemporal approach. After the CSF removal through the Sylvian fissure, the gentle elevation of the left temporal lobe allowed the visualization of the feeders and the pulsating venous sac. After the complete obliteration of the feeding arteries and removal of the nidus, the interruption was verified by using doppler sonography and intraoperative angiography. Postoperative course was uneventful. The infant was discharged without deficit on the 30th postoperative day. The authors discussed the embryological implications of this type of AVM and the role of endovascular surgery. PMID- 8361572 TI - [Two cases of metastatic brain tumor treated by interstitial brachytherapy]. AB - The prognosis of patients with metastatic brain tumor is very poor. Median survival of these patients has ranged from 1 month with no therapy, to 2 months with steroid, and from 3 to 6 months with brain radiation therapy of the whole brain. A more recent study comparing radiation therapy alone with surgery plus radiation, has shown good results in the combined surgery and radiation therapy group. But surgical excision is usually limited to patients with a surgically accessible solitary metastasis. And therapeutic options are limited once the tumor recurs locally after whole brain irradiation. Interstitial irradiation allows the delivery of a high dose of localized irradiation in the area of tumor recurrence with minimal risk of radiation damage to the surrounding brain tissue. But brachytherapy for brain metastasis has been performed in few cases. We reported two patients with unresectable metastatic brain tumors who were successfully treated with iridium-192 interstitial brachytherapy, and we discuss the strategy of the treatment. Case 1: A 78 year-old-man underwent a total gastrectomy for gastric cancer. Five months after surgery, he developed right hemiparesis. CT scan revealed a left occipital tumor with massive brain edema and a tiny nodule of tumor in the left thalamic region. The primary site was well controlled and no systemic disease was seen during subsequent whole body examination. The occipital lesion was surgically excised and he received a postoperative radiation therapy of 50 Gy to the whole brain. The thalamic tumor had not responded to the irradiation and the size of tumor rapidly increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361573 TI - [A case of a giant epidermoid cyst on the occipital scalp]. AB - The authors report a case of a 61-year-old woman presenting with a giant mass on the occipital scalp. The patient had no neurological deficits and was of normal intelligence. The lesion was soft and covered by an unremarkable epidermis. The preoperative radiologic evaluation was made by CT, MR Imaging, and by cerebral angiogram. The mass produced an inhomogeneously low-intensity signal involving also a high-intensity signal. It was shown, on the T1 weighted image, that it did not communicate with the intracranial space, and there was no gadolinium-enhanced lesion. MR Imaging was superior to CT in the evaluation of the giant mass on the scalp and was particularly useful in surgical planning. At surgical resection, a soft fluffy, white-colored tumor which measured 16 x 10 x 7 cm was totally removed. Pathological diagnosis of the tumor was epidermoid cyst. PMID- 8361574 TI - [A case of intra- and extracranially extensive metastatic brain tumor of tracheal cancer origin]. AB - The authors report a case of metastatic brain tumor of tracheal cancer origin, itself a rare condition. A 55-year-old man was admitted with complaints of headache, atonic seizure of left lower limb and right temporal swelling. On admission, the patient had left recurrent nerve palsy. CT scan displayed right temporal bone destruction and ring-enhanced mass. MRI disclosed that the mass contained an inner necrotic region and a perifocal edema. Right common carotid angiogram revealed that the tumor was fed only by narrowed vessels of the middle meningeal artery. Subtotal removal of the tumor was performed, and histological examination revealed cranial metastasis of tracheal squamous cell carcinoma. Postoperative course was uneventful, and the patient underwent medical treatment for the primary lesion before post-operative brain-irradiation. PMID- 8361575 TI - [Delayed vasospasm complicated with the postoperative stage of the meningioma: a case report]. AB - Though it has been reported infrequently that delayed vasospasm may appear in head-injured patients, it is rather rarer to see it as a complication arising from tumor removal. Such a case was presented and gave rise to speculation of a possible underlying pathophysiology. A 46-year-old female patient was admitted to our neurosurgical service, complaining of aching pain in the forehead. No neurological deficits were elicited on admission. CT scans as well as MR imagings confirmed the existence of a left sphenoid wing meningioma whose gross total removal was accomplished. She was doing well till the 3rd postoperative day, when she developed transcortical motor aphasia. 123I-IMP SPECT revealed low perfusion over the left middle cerebral artery territory, and CT scans also showed low density areas in the same region, including the putamen, corona radiata and temporal lobe on the left side. Left carotid angiography disclosed diffuse arterial narrowings involving C1, C2, A1 and M1 portions. The authors suspect that indirect injury to those arteries and/or some kind of inflammatory process might have played a role. PMID- 8361576 TI - [Radiation-induced cerebrovasculopathy: a case report and review of the literature]. AB - We reported a case of a patient who suffered from a cerebrovasculopathy after irradiation therapy for astrocytoma located at the left temporal lobe. An eleven year-old boy who presented himself with headache and vomiting as his chief complaints received partial removal of a tumor. Histological diagnosis of the tumor was astrocytoma (grade II). His preoperative cerebral angiograms showed mass sign solely, without stenosis or occlusion of the cerebral vessel. Postoperatively, he was treated with irradiation therapy involving the whole brain with a total of 30 Gy, and gamma knife therapy. Six months after irradiation, he started suffering from frequent cerebral ischemic attacks, but there was no regrowth of the tumor visible on CT scans. Cerebral angiograms were made again, and revealed multifocal stenoses in the bilateral internal carotid arteries, middle cerebral arteries, and the anterior cerebral artery. His symptoms did not improve after conservative treatment with steroids, calcium antagonist, or low molecular weight dextran. Although he received a superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses bilaterally, multiple cerebral infarctions appeared. Although irradiation therapy is acceptable in patients with brain tumor, a cerebrovasculopathy after irradiation should be considered as one of the most important complications, and the risk incurred by irradiation therapy should lead to more careful consideration and caution when treating intracranial brain tumors, especially in children. From our experience, the usefulness of bypass surgery for radiation-induced cerebrovasculopathy is still controversial. PMID- 8361577 TI - Assessment of 8-OH-DPAT induced spontaneous tailflicks as an in vivo model of 5 HT1A function in young rats. AB - Spontaneous tailflicks, measured as elevation of the tail above the body axis in restrained animals, have been studied in both adult and young rats. The selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), induced dose related increases in spontaneous tailflicks in adult (> 60 days) male rats. These responses were antagonised by the 5-HT1A antagonists (-)-propranolol and (-) pindolol. 8-OH-DPAT (1 mg/kg) induced tailflicks could be observed in 30, 25 and 20 day old male rats and were also antagonised by (-)-propranolol and (-) pindolol although drug-induced rotation of the 20 and 25 day old animals hindered assessment. At 14 and 10 days, 8-OH-DPAT (1 mg/kg) produced Straub tail responses which precluded the observation of tailflicks. Lower doses of 8-OH-DPAT, which did not elicit Straub tail in these younger animals also failed to produce tailflicks. Thus 8-OH-DPAT induced spontaneous tailflicks reflect in vivo activation of 5-HT1A receptors in adult and 30 day old male rats but are inappropriate for the study of 5-HT1A mediated behaviour in younger animals. PMID- 8361578 TI - Opioid action on spinal cord reflexes due to dorsolateral pontine tegmentum stimulation. AB - Electrical stimulation of the dorsolateral pontine tegmentum (DLPT) produces phasic facilitatory and inhibitory actions on the lumbar spinal monosynaptic reflexes (MSRs) of both flexor and extensor muscle nerves in the decerebrate cat. Naloxone, an opioid receptor antagonist, given intravenously or intraspinally enhanced the DLPT-induced potentiation of MSRs in most of the reflexes studied. However, systemic naloxone had no significant effect on the unconditioned MSR of the spinal cord. Intraspinal microinjections of naloxone significantly attenuated the DLPT-induced inhibition of MSRs of both flexors and extensors, similar to the action of systemic injection of naloxone, indicating a direct opioid action at the spinal ventral horn level upon DLPT stimulation. Results of the present experiment further support the anatomical finding that there are pontospinal enkephalinergic pathways in the cat, and indicate that these descending pathways modulate spinal motor outflow. PMID- 8361579 TI - Inhibitory effects of the 5-HT1A agonists, 5-hydroxy- and 5-methoxy-(3-di-n propylamino)chroman, on female lordosis behavior. AB - Sexually receptive, intact, proestrous rats were infused bilaterally into the ventromedial nucleus of the hypothalamus with one of several serotonin (5-HT) agonists and with the endogenous ligand, 5-HT. Serotonin (2000 ng) and the 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin [8-OH-DPAT (200 ng)], 5-methoxy 3-(di-n-propylamino)chroman [5-MEO-DPAC (200-2000 ng)] and 5-hydroxy-3-(N-di-n propylamino)chroman [5-OH-DPAC (200-2000 ng)] inhibited female lordosis behavior within 10 min of the infusion. The rank order of the effectiveness of these compounds was 8-OH-DPAT > 5-OH-DPAC > or = 5-MEO-DPAC > 5-HT. The nonselective 5 HT agonist, 1-(m-trifluoromethyl) piperazine [TFMPP (2000 ng)], did not reduce lordosis behavior. In addition to their reduction of lordosis behavior, the 5 HT1A agonists elicited resistive behavior toward the male's attempts to mount. There were minimal effects of the 5-HT1A agonists on either quality of the lordosis reflex or on proceptivity. However, rats pretreated with TFMPP and infused with 8-OH-DPAT 1 hr later, did show a transient suppression of lordosis quality. These results provide further evidence that the ventromedial nucleus of the hypothalamus contains 5-HT1A sites, the activation of which reduces lordosis behavior in regularly cycling, proestrous rats. PMID- 8361580 TI - The effects of adrenalectomy and ovariectomy on the behavioral and hypothermic responses of rats to 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). AB - The aim of this study was to determine the effects of sex, corticosterone and oestradiol-17 beta on the hypothermia and motor behavioural syndrome induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermia, but not the behavioural syndrome induced by 8-OH-DPAT was significantly greater in female compared with male rats. Adrenalectomy in male rats enhanced the hypothermic response, an effect prevented by corticosterone implants. Ovariectomy significantly attenuated the hypothermia induced by 8-OH-DPAT, an effect prevented by oestradiol-17 beta implants. Neither type of steroid manipulation affected the behavioural syndrome. These results show that sex, corticosterone and oestradiol-17 beta modulate the hypothermic response to 8-OH-DPAT in the rat, with corticosterone and oestradiol-17 beta having opposing effects. PMID- 8361581 TI - Role of calcium ions in dopamine release induced by sodium cyanide perfusion in rat striatum. AB - We have previously reported a transient and remarkable increase in dopamine (DA) release in the rat striatum during application of 2 mM sodium cyanide (NaCN) through a brain microdialysis membrane. In the present study we examined the involvement of extracellular Ca2+ in this response. Rats were divided into 4 groups. In the NaCN group a microdialysis probe inserted into the striatum was perfused with Ringer's solution containing 2 mM NaCN for 60 min. The Ca2+ free + NaCN group was subjected to perfusion with NaCN dissolved in Ca2+ free Ringer's solution, and the CdCl2 + NaCN group with the same plus 0.3 mM CdCl2 (a non specific Ca2+ channel blocker). In the NaCN and Ca2+ free + NaCN groups DA levels in the dialysates increased to 36- and 44-fold of the control level, respectively, while this was suppressed to only a 16-fold increase in the CdCl2 + NaCN group. In response to a 100 mM KCl perfusion given 3 hr later DA levels were increased (22-fold) in the control group. On the other hand this response was inhibited in the NaCN group (3-fold), but not in the other two groups. An in vitro study with striatal slices showed a gradual increase in intracellular Ca2+ during incubation with 2 mM NaCN. These results suggest that excessive influx of extracellular Ca2+ during NaCN perfusion may contribute partly to the increase in the extracellular DA level in the striatum, and also to the suppression of a DA increase in response to high K+ stimulation observed 3 hr later. PMID- 8361582 TI - Tolerance and cross-tolerance to the antinociceptive effects of [D-Arg2] dermorphin tetrapeptide analogue and morphine. AB - Rats were given repeated subcutaneous injections of [D-Arg2, Sar4]-dermorphin (1 4) [DAS-DER-(1-4)] and/or morphine over a period of 4 or 7 days. Antinociception was determined at 90 min for DAS-DER (1-4) and 30 min for morphine after each morning injection (9:00 a.m.), using the tail-flick and digit pinching tests in rats. Subcutaneous administration of DAS-DER (1-4) and morphine produced the development of antinociceptive tolerance, respectively. A marked tolerance to DAS DER (1-4) and morphine was seen in rats made tolerant to morphine. However, administration of morphine produced no significant decrement in the antinociceptive activity in rats made tolerant to DAS-DER (1-4). These results suggest that the site of action of DAS-DER (1-4) may be more limited than that of morphine in the nociceptive pathways, for lack of its antinociceptive efficacy in morphine-tolerant rats. PMID- 8361583 TI - Met-enkephalin-Arg6-Phe7 in spinal cord and brain following traumatic injury to the spinal cord: influence of p-chlorophenylalanine. An experimental study in the rat using radioimmunoassay technique. AB - The possibility that trauma to the dorsal horn may affect the release and distribution of enkephalin was examined using the opioid peptide Met-Enk-Arg6 Phe7 (MEAP) as a marker in a rat model. The peptide content of samples of spinal cord and whole brain was measured using a radioimmunoassay (RIA) technique. In addition, the possible functional relation between this peptide and serotonin was evaluated using a pharmacological approach that included depletion of endogenous serotonin. A focal trauma to the right dorsal horn in the T10-11 segments (2 mm deep and 5 mm long) markedly modified the content of MEAP of the adjacent rostral and caudal segments of the cord, as well as the content of MEAP of the brain. Depletion of serotonin with p-CPA (an inhibitor of the synthesis of serotonin) significantly elevated the content of MEAP in the whole brain without affecting the regions of the spinal cord (except T9 level which showed a 25% decrease from an intact control group). Trauma to the spinal cord in the serotonin-depleted animals did not alter the content of MEAP further, as compared to a p-CPA-treated but untraumatized group. These results indicate that enkephalin (i) participates in the pathophysiology of spinal cord trauma and (ii) suggest that the peptide is somehow functionally related with serotonin. PMID- 8361585 TI - Child abuse and basic training. PMID- 8361584 TI - Prenatal cocaine exposure: decreased sensitization to cocaine and decreased striatal dopamine transporter binding in offspring. AB - Pregnant mice were treated with cocaine, 10 mg/kg/day, during days 13 to 20 of gestation. Cocaine sensitization and dopamine transporter binding were evaluated in offspring at 6 weeks of age. Sensitization, defined as the increase in activity after 5 injections of cocaine compared to 1 injection, was reduced in cocaine-exposed mice. Dopamine transporter binding in striatum was also significantly reduced in cocaine-exposed mice compared to controls. PMID- 8361586 TI - Educating about military field/medical duty. PMID- 8361587 TI - Outpatient treatment of posttraumatic stress disorder. PMID- 8361588 TI - Forensic dental identification of casualties during Operation Desert Storm. AB - Forensic dental identification of casualties during Operation Desert Storm was performed at the Dover Port Mortuary, Dover Air Force Base, under the auspices of the Office of the Armed Forces Medical Examiner. A total of 251 dental identifications were attempted and 244 individuals were positively identified by dental comparison. The panoramic radiographs on file at the Central Panograph Storage Facility were the primary antemortem records utilized in establishing the dental identification. The inability to establish a positive dental identification was most often the result of a lack of available antemortem dental records. PMID- 8361589 TI - The role of military medicine in military civic action. AB - We are moving into an era when U.S. military forces will be called upon frequently to perform military civic action (MCA) projects. Such projects, have been used successfully and unsuccessfully, primarily in the areas of medicine and engineering, to enhance the standing of military forces with indigenous populations. However, the available criteria for planning and assessing MCA projects are not widely known. These related and overlapping criteria are supported by facts, interpretative data, anecdotes, and common sense, but none can be considered absolute. Selected criteria are defined, reviewed, and illustrated with examples of past successes and failures. PMID- 8361591 TI - Immunization status of a military dependent population. AB - The immunization status of active duty pediatric dependents served by the National Naval Medical Center was surveyed to estimate the degree to which this group was in compliance with immunization requirements. Four hundred sixteen patients who presented consecutively to a pediatric acute care clinic had their medical and immunization records screened. Ten percent of patients did not have complete records of immunization. Of the 375 patients remaining, 52 (13.9%) were deficient in one or more required immunizations based on their current age. The highest rates of delay were seen for the Haemophilus influenza vaccine followed by measles, mumps, rubella, and diphtheria, tetanus, and pertussis. The most common reason for missing immunizations was parental unfamiliarity with the recommended schedule. This study suggests that a significant number of dependents in our catchment area were delayed in immunization and that accurate record keeping and patient education about immunizations needs to be improved. PMID- 8361590 TI - Nutritional status of rural Bolivian children. AB - While providing health care in rural Bolivia, 349 children under 4 years old were seen. Height and weight were measured and demographic data obtained. The purpose was to describe the prevalence of malnutrition and its associated socioeconomic factors. The sample included Mataco Indians and Bolivians of European or of mixed descent. Using international standards, 21% of the children had weight below the fifth percentile for age; 27% had height below the fifth percentage for age; 17% were below the fifth percentile for weight/height. Malnutrition was more common in younger children (peak prevalence in 1-2 year olds). Malnutrition was associated with race and water source, but not with family size, literacy, immunizations, meals per day, or deaths in family. Attempts to improve nutrition should focus on the youngest children. PMID- 8361592 TI - The military physician and conservation of force. AB - The military physician, while uniquely qualified to command medical units, is challenged during military operations to "conserve the fighting strength" of the combat arms units he supports. To meet the obligations of his command, the military physician must involve himself in the training, planning, and execution of his unit's specific mission. In peacetime, this involvement must be given priority and include field training exercises as well as continuing education. PMID- 8361593 TI - Israel defence forces experiences with treatment of POWs and families: an innovative multifaceted treatment model. AB - This paper attempts to provide an integrative, multifaceted treatment approach for the surviving POW and his family. The model takes into account the individual, family, interpersonal, and community effects of captivity from the time of captivity until 1 year later. Ramifications of this model are discussed. PMID- 8361594 TI - Hemarthrosis of the clinically stable knee due to sports and military training in young recruits: an arthroscopic analysis. AB - Findings of an early arthroscopy performed in 108 consecutive hemarthrotic and clinically stable knees were analyzed. The patients were young conscripts, the mean age being 19.9 years. Fifty-seven of the knees were injured during military training, 36 in different sports activities, 9 at falls, and 6 in motorbike accidents. The lesions were divided into "primary" (lesions needing operative treatment or the supposed most common lesions in incidence) and "secondary" (other lesions). An average of 1.6 lesions were observed per knee. Dislocation of the patella was the most common diagnosis in 38 (35%) cases. Dislocation of the patella was associated with military exercise (p < 0.001). Lesions of the anterior cruciate ligament (ACL) were observed in 37 (34%) cases. ACL ruptures were related to sport activities (p < 0.0001). PMID- 8361595 TI - Utilization of occupational therapy in combat stress control during the Persian Gulf War. AB - This article chronicles the deployment and subsequent utilization of occupational therapy personnel in support of combat stress control operations during the Persian Gulf War. It presents a discussion of occupational therapy's military history, evolving doctrine, and selected training experiences which led to the attachment of occupational therapy personnel to the 528th Medical Detachment (Psychiatric OM Team). A description of roles, functions, methods of operation, and lessons learned help to clarify the direction of occupational therapy in its future wartime mission. PMID- 8361596 TI - Health promotion in a shrinking military: the call for structural integration and a conceptual systems approach. AB - The evolution of health promotion in the military is reviewed and contrasted with developments in private sector activities. Programs in both arenas generally take a mechanistic, mortality and risk factor-based approach which targets lifestyle and behavioral change. In the military, that has resulted in a fragmentation of function and perception in the line and medical communities about health promotion. A "world view" model and a conceptual systems approach to health promotion are presented in which human resources, occupational health, life style, and health benefits programs are integrated to achieve efficiencies in program management, decreased mortality, and reduced medical care costs. PMID- 8361597 TI - Diarrheal and respiratory disease aboard the hospital ship, USNS-Mercy T-AH 19, during Operation Desert Shield. AB - Diarrhea and respiratory disease were common problems among ground troops deployed to the Middle East during Operation Desert Shield. In order to determine the prevalence and impact of diarrheal and upper respiratory disease among shipboard personnel during this period, an epidemiologic survey was conducted on the hospital ship, USNS Mercy T-AH 19. An episode of acute diarrhea was reported by 46% of the surveyed population, and 79% reported upper respiratory symptoms. Six percent of personnel were temporarily unable to perform scheduled duties due to gastrointestinal symptoms and 7% due to respiratory symptoms. Officers were at increased risk of experiencing an episode of diarrhea, and female crew members more often reported respiratory complaints. Improved strategies to prevent diarrhea and respiratory disease among shipboard personnel are needed. PMID- 8361598 TI - A descriptive study of care processes using total quality management as a framework in a USAF regional hospital emergency service and related services. AB - The purpose of this descriptive study was to investigate access to care processes in a military regional hospital Emergency Service (ES) and related services using a Total Quality Management framework. Tabulations of demographic survey data revealed that the ES is used mainly as a primary care clinic, with a greater proportion of pediatric care provided during peak hours. An analysis of patterns of care processes in the organizational system revealed that there was little in common between Total Quality Management and Continuous Quality Improvement principles and the care processes. The results of the analysis lend support to the proposed USAF decentralized, coordinated health care system with more authority and control given to local commands and emphasis upon increased responsibility and accountability within professional and beneficiary communities. PMID- 8361599 TI - Primary malignant tumors of the small intestine: a retrospective review in a military hospital. AB - Small intestinal malignancies are rare and highly variable in clinical presentation. Thirteen cases were found in the Tumor Registry of Naval Hospital, Oakland, California (NHO). We compared the NHO incidence to that of other civilian institutions. Suspicion of these tumors is necessary for early diagnosis and appropriate therapy. We advocate that data from a large number of hospitals be pooled to improve quality of care and better understand possible carcinogenic factors. This review is intended to share our findings and to stimulate further studies. PMID- 8361600 TI - Preparation for Desert Storm: expansion of an overseas Air Force hospital pharmacy to handle casualties. AB - The planning and execution for contingency pharmacy services in support of Operations Desert Shield/Desert Storm in an overseas Air Force Medical Center are described. These operations presented the staff with far different challenges than the contingency support plan that had been in place for several years. That plan focused medical operations based on armed conflict in Central Europe. With conflict now imminent in the Persian Gulf, over 8 hours flying time away from our facility, our priorities and mission changed tremendously. This conflict demanded prompt action by the Department of Pharmacy to ensure comprehensive services in support of Operations Desert Shield/Desert Storm without interruption of services to the local military community. Pharmacy planning focused on four basic areas: (1) supply requirements, (2) contingency staffing requirements, (3) expansion of inpatient pharmacy services, and (4) modifications to outpatient pharmacy services. A modified contingency plan assured professional pharmaceutical services for over 3,000 patients suffering injuries in the 12 months American forces were deployed to the Persian Gulf. PMID- 8361601 TI - A review of lower limb overuse injuries during basic military training. Part 1: Types of overuse injuries. AB - Lower limb injuries present the greatest source of medical problems during basic military training. These main overuse lower limb injuries, anterior compartment syndrome, stress fractures, Achilles tendinitis, plantar fasciitis, shin splints, and chondromalacia patellae, are reviewed with respect to current knowledge of rates, diagnosis, and treatment. Part 2 shall review possible etiological factors involved in the causation of these injuries. PMID- 8361602 TI - A review of lower limb overuse injuries during basic military training. Part 2: Prevention of overuse injuries. PMID- 8361603 TI - The "un-comfort-able": making sense of adaptation in a war zone. AB - Unanticipated deployment of medical personnel from a fixed medical facility to a hospital ship creates significant psychological anxiety. Analysis of the stressors which the August 1990 deployment of the USNS Comfort in support of Operation Desert Shield/Storm precipitated in its crew are detailed and coping strategies are discussed. Recommendations to assist personnel in adapting to future deployments of this type are made. This unique event demonstrates the continued importance of applying the principles of social psychology to operational military events preventively. PMID- 8361604 TI - National Guard training: Fort Irwin MEDDAC experience during Operation Desert Storm. AB - The expansion of the USA MEDDAC, Fort Irwin, California, during Operation Desert Storm is described. During Operation Desert Storm, Fort Irwin and the National Training Center was responsible for training the 48th Separate Infantry Brigade National Guard from Georgia. The impact of this training upon the MEDDAC is described. PMID- 8361605 TI - Undiagnosed shrapnel of the tongue. AB - A case of a large metal fragment in the tongue is reported in a soldier injured in Operation Desert Storm. The fragment was not diagnosed for 57 days as the patient was evacuated through multiple U.S. Army medical facilities for other injuries. Diagnosis and treatment of the case are discussed. PMID- 8361606 TI - Unequal refractive error and high astigmatism associated with orbital lymphangioma. PMID- 8361607 TI - [Clinical hemorrheology and arterial hypertension]. AB - In order to have a good haemorheological approach to hypertensives, we have put together a review with haemorheological subjects and with the relationships between plasmatic and haematic viscosity and hypertension in relation to pathophysiology, diagnosis, prognosis and treatment. In this review we deal with: (1) Clinical haemorheology. (2) Haematic viscosity. (3) The relationship between haemorheology and hypertension and between antihypertensive drugs and haemorheology. The study of viscosity and erythrocytes deformability, and of erythrocytes and platelets stickiness could pharmacologically correct the haemorheological disorders which can be some of the causes of hypertension. PMID- 8361608 TI - [Evolution of pacing modes in patients with implanted pacemakers. Personal considerations on a case load of 171 patients]. AB - In this study retrospectively analyse pacemaker-implantation activity carried out during the last 5 years at the Laboratory of Electrophysiology, affiliated with the Cattedra di Cardiologia of the University of Naples--II Ateneo. Evolution in pacing modes is considered with regard to the patient age, the underlying pathologies and the technical progress in the field. The study has been performed in our laboratory, which is fit up for electrophysiologic studies and implantation of either temporary or permanent pacemakers. Patients included in this study have been implanted in our laboratory either for urgency or for election. They have been retrospectively divided into two groups (age < 65 yrs, 129 patients, and age < 65 yrs, 42 patients); in addition the patients have been classified according to the pathology leading to the implantation: atrio ventricular block (second degree or third degree), low frequency fibrillation, sick sinus syndrome and carotid sinus syndrome. 171 patients have been examined, of whom 129 > 65 yrs. and 42 < 65 yrs. As for the pacing indication, 54 were atrio-ventricular block (56.1%), 50 were sick sinus syndrome (31.6%), 20 low frequency fibrillation (11.7%), and 1 was carotid sinus syndrome (0.6%). The ratio between single- and dual-chamber pacemakers has been progressively changing: in 1987 we implanted 33 single-chamber and no dual-chamber pacemaker, compared to 7 single- and 23 dual-chamber pacemaker implanted in the last year. This trend is in good agreement with literature data. PMID- 8361609 TI - [Evaluation of regression of left ventricular hypertrophy after antihypertensive therapy. Comparative echo-Doppler study of ace inhibitors and calcium antagonists]. AB - This study evaluates 33 patients suffering from mild-moderate arterial hypertension (systolic blood pressure over 160 mmHg; diastolic blood pressure over 95 mmHg) and with concomitant indications of concentric left ventricular hypertrophy at echocardiography. Twenty patients completed the trial according to the criteria established in the protocol and were found suitable for evaluation of the results at the end of the study. Ten patients were treated with 40 mg of nifedipine retard tablets, administered twice (1 x 20 mg tablet twice daily) and 10 patients were treated with a single administration of 20 mg quinapril (1 x 20 mg tablet per day). Total follow-up was performed for one year (variability 12-14 months) with evaluation of the pressure response at 1-3-6-12 months and clinical evaluation and echocardiographic control for comparison with the baseline at the end of the study. The left ventricular mass values measured at the end of the study presented a statistically significant reduction (p < 0.001) with respect to the baseline in both groups. In the patients treated with quinapril the percentage regression of left ventricular hypertrophy was 19.39%, and slightly higher (19.5%) in the patients treated with nifedipine. Finally, although the series is perhaps too limited to draw conclusions, the finding that the indicators of diastolic filling of the left ventricle improved, and, in particular, were correlated with an increase in the speed of the first fast filling phase, and thus that there was a partial improvement in left ventricular compliance, is important. PMID- 8361610 TI - [Critical ischemia of the lower limbs: pathogenesis, clinical course and therapy. Results of authors' experience in 337 cases]. AB - The definition of an ischaemic condition at lower limb level, may imply any different degree of the pathology, starting from a simple chronic slight claudication up to a severe ischaemia. Critical Limb Ischaemia is the term defined to identify an ischaemic condition, which endangers the limb or part of a limb and requires a prompt and appropriate treatment. However the pathophysiology of this condition remains to be well established and depends on various vascular factors. For the European Working Group on Critical Limb Ischaemia (Berlin 1989, Rudesheim 1991) the definition is strictly restricted to Fontaine's stage III B and IV, while in our opinion the definition could be very simple in all the patients with a prognostic limb-threatening condition (for localization and wide extension of the lesions) independent of the Fontaine's stage, which are going towards a future amputation if radical improvement of blood flow cannot be achieved with an adequate revascularization. In our five year late experience, we observed and surgically treated 337 patients with CLI (74% males and 80% atherosclerotic lesions). We discuss the preoperative findings, diagnostic procedures, surgical techniques and relate results. PMID- 8361611 TI - [Current role of extra-anatomical revascularization of the lower limbs]. AB - In vascular reconstructive surgery of the lower limbs for aorto-iliac disease the first choice procedure is TEA or aorto-femoral bypass. In "high risk patients" alternative procedures like extra-anatomical bypass (axillo-femoral or femoro femoral bypass grafts) are available. In some cases, such us infection of a retroperitoneal prosthesis, an axillo-femoral bypass is mandatory in order to obtain revascularization of the lower limbs. In this article we report our late experience in this surgery and our opinion on the correct indication for the use of these procedures. PMID- 8361612 TI - [Cor triatriatum associated with inter-atrial defect: diagnosis by transesophageal echocardiography]. AB - Cor triatriatum (CT) is a rare malformation consisting of a fibromuscolar membrane that subdivides the left atrium in a postero-superior (or accessory) chamber and an antero-inferior chamber (true left atrium, containing the left atrial appendage). In its classic form, the accessory chamber receives the pulmonary veins and communication with the left atrium is accomplished by way of one or more fenestrations in the membrane. The malformation is usually isolated, but in about one in four patients is associated with other congenital defects of a complex nature. We describe a case of CT associated with atrial septal defect, in which transthoracic echocardiography failed to document the existence of CT membrane, while this abnormality was clearly seen and defined by use of transesophageal echocardiography. The patient was a 26 year-old girl, presented at our outpatient clinic after an episode of palpitations and dyspnea, which lasted for two hours. She suffered of mild dyspnea on exertion during the last three months. Physical examination revealed the typical findings of an atrial septal defect (ASD), and the electrocardiogram revealed right bundle branch block. The two-dimensional echocardiography disclosed an ostium secundum ASD with left to right shunt; dilatation of the right cavities; paradoxical movement of the interventricular septum. A small linear echo originating from the lateral wall of the left atrium, with no evidence of turbulent flow on pulsed wave Doppler and color flow examination, was interpreted as an artifact. Transesophageal echocardiography clearly visualized a tense, bulging membrane separating left atrium into two chambers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361613 TI - [Ventricular fibrillation during stress test on a treadmill. Apropos of a case]. AB - A case of ventricular fibrillation occurring in the recovery phase of treadmill exercise test is described. A 64-year-old man was admitted to the hospital because of chest pain. The resting electrocardiogram was normal, but during a stress test (Bruce protocol) ventricular ectopic beats and ischemic S-T depression were observed. The echocardiogram showed septal hypertrophy and septal and apical hypokinesia. Ten days later he, during antianginal therapy, underwent treadmill exercise testing. In contrast with the previous stress test, ventricular ectopic beats decreased during the effort, but the S-T segment depressed, at the third step, with mild chest pain and hypotension. While angina and electrocardiogram improved, suddenly ventricular fibrillation developed. The patient was successfully resuscitated with electrical defibrillation, with a 350 joules shock. Echocardiogram was unchanged; serum enzymes were slightly modified (secondary to DC-shock). The ischemic changes observed at the electrocardiogram in the anterior wall within seven days returned in the normal range. Ten days later the patient underwent cardiac catheterization. At ventriculography the posterior and diaphragmatic wall was diskinetic, ejection fraction was 70%; a complete occlusion of the right coronary artery at the origin, a critical stenosis of left descending artery, with occlusion in the middle tract were found. Circumflex artery was occluded at the origin with omo-etero-coronary collateral channels. Twenty days later, he had a successful bypass surgery. Postsurgical echocardiogram revealed a moderate depression of ejection fraction (41%), inferior diskinesia, apical hypokinesia, mild mitral regurgitation. The patient was discharged with digitalis, nitrates, aspirin and amiodarone for prophylactic treatment of paroxystic atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361614 TI - [Vascular complications in drug addicts. Intermittent claudication in a HIV seropositive heroin addict]. AB - The widespread use of heroin has revealed the growing life-threatening complications consequent on drug practice. The effects of heroin on the cardiovascular, pulmonary, renal and central nervous system have been well described in medical literature, but the vascular complication of chronic occlusive arterial disease of the lower limbs is rare. We report a case of a young female patient who was a chronic drug addict for over five years, with concomitant serum positiveness for HIV infection. The etiologic and pathogenetic mechanisms of such an uncommon vascular complication are discussed on the basis of the existing literature. PMID- 8361615 TI - [Primary mesothelioma of the pericardium with long-term survival]. AB - We report the case of a 52-year-old man admitted to our Hospital for a massive pericardial effusion already discovered at an X-ray examination of the chest more than one year before, but never submitted to further investigation. Four months after a first surgical intervention of "pericardial windowing" and a drainage of 1700 ml of clear pericardial fluid, the patient was again hospitalized because of cardiac tamponade and underwent open pericardial drainage. At inspection, the pericardium and the myocardial muscle were fused in a single mass that at histological examination was discovered to be a primary mesothelioma of the pericardium, epithelial type. We discuss the clinical course and review the scientific literature inherent in these rare cases of primary neoplastic diseases of the heart. PMID- 8361616 TI - Optimalized in vivo production of monoclonal antibodies in mouse ascitic fluid. AB - The note contains a brief summary of the method in use at the National Institute of Public Health for the production of monoclonal antibodies in mouse ascitic fluid. This method of obtaining large amounts of monoclonal antibodies is widely used. Refining the in vivo method and increasing the yield from each mouse could result in a reduction of the number of animals used. PMID- 8361617 TI - Time variations in injury incidence. AB - STUDY OBJECTIVE: to present time variations in the incidence of injuries on a community level. POPULATION AND METHODS: all injuries which occurred in a defined population of the municipality of Harstad were registered prospectively from 1 January 1986 to 31 December 1991. Variations over time in monthly incidence of seven types of injuries (home, traffic, street, sports, work, other, unknown) were analysed by the Autoregressive Integrated Moving Average Analysis (ARIMA). RESULTS: a total of 9,685 injuries was registered during the six year follow-up period. No significant secular trend was observed for any of the analysed types of injuries. Series of monthly incidence of traffic, street, and sports injuries showed seasonal-dependent variations. Incidence of traffic injuries was highest during the summer months, while incidence of sports and street injuries was highest during the winter months. CONCLUSIONS: both the existence of seasonal dependency in injury incidence and the relatively high random variations in monthly injury incidence imply that evaluation of community based injury control programmes should include incidence during at least a one year period before the intervention has started. PMID- 8361618 TI - Heat shock partially protects rat pheochromocytoma PC12 cells from amyloid beta peptide toxicity. AB - Rat pheochromocytoma PC12 cells are killed by amyloid beta protein (ABP), a component of plaques and other amyloid deposits in Alzheimer's disease. To investigate the possibility of protection from ABP toxicity by induced heat shock proteins (hsps), PC12 cells were heat treated for 60 min at 42 degrees C. The stress response of the PC12 cells was examined at the protein level using hsp72 specific monoclonal antibodies. Hsp72 immunoreactivity was highly induced following heat treatment. The toxic effect of the beta 25-35 ABP peptide fragment, the major cytotoxic sequence within ABP, was reduced in heat pretreated PC12 cultures. These data indicate a protective role of hsps in neuronal cells exposed to ABP. PMID- 8361619 TI - Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. AB - In healthy human adults, cerebral concentrations of oxygenated hemoglobin ([HbO2]) and deoxygenated hemoglobin ([HbR]) were assessed during brain activation using near infrared spectroscopy (NIRS). Measurements were made either in the frontal cortex (n = 10) during performance of cognitive tasks or in the occipital cortex (n = 6) during visual stimulation (flash-light exposure, picture observation). The typical findings during brain activation were an increase in [HbO2] and a decrease in [HbR]. We demonstrate that these findings are not due to alterations in skin blood flow. NIRS is a simple bedside technique for the assessment of hemodynamic alterations accompanying brain activation. PMID- 8361620 TI - The effect of ketamine anesthetic induction on muscle responses to transcranial magnetic cortex stimulation studied in man. AB - In man, an anesthetic agent that induces surgical anesthesia with minimal influence on descending pyramidal tract activity remains to be found. Anesthesia with ketamine allows recording of stable compound muscle action potentials (CMAPs) to single transcranial magnetic stimulations of the motor cortex (CortStim) in monkeys. This report describes the findings in 5 patients, where CMAPs to CortStim were recorded from the right hypothenar during anesthesia induction with ketamine. The agent was injected intravenously every 90 s in 6 steps of 0.5 mg up to a maximum of 3 mg/kg body weight (BW). Surgical anesthesia was achieved after ketamine injection of 1.5 (n = 4 patients) or 2.0 mg/kg BW (n = 1). In the five individuals tested, CMAP amplitudes and latencies (mean; range) were 2.6 (1.6-5.8) mV and 22.8 (20.4-24.6) ms before induction, and 1.6 (0.3-4.7) mV and 23.5 (21.7-24.5) ms after administration of the maximum dose. The paired differences (mean +/- 1 S.D.) were 0.8 +/- 0.6 mV and 1.0 +/- 0.8 ms and were statistically not significant (n = 5, P = 0.1, Wilcoxon-test). With ketamine as a single anesthetic induction agent CMAPs to single CortStim remain easily recordable even in dosages higher than those necessary to induce surgical anesthesia. All other previously tested anesthetic agents suppress CMAPs to CortStim as soon as the patient is unconscious. PMID- 8361621 TI - Measles virus-induced hippocampal neurodegeneration in the mouse: a novel, subacute model for testing neuroprotective agents. AB - The hamster neurotropic (HNT) strain of measles virus causes non-inflammatory encephalopathy in Balb/c mice, associated with neurodegeneration in hippocampal CA1 and CA3 regions. This loss of pyramidal cells can be prevented by twice daily systemic treatment with 1 mg/kg dizocilpine (5-methyl-10,11-dihydro-5H dibenzo(a,d)cyclo-hepten-5,10-imine maleate; MK-801) for 7 days. By varying the MK-801 treatment protocol, we now found that drug administration during the last 4 days prior to sacrifice (i.e. days 4-7 post inoculation, p.i.) is essential for neuroprotection. In contrast, MK-801 treatment during the first days (days 0-4 p.i.) did not prevent the neuronal necrosis. These data suggest that the concentration of an excitotoxic factor in the mouse brain increases after virus inoculation, reaching toxic levels by days 4-5 p.i. This novel 'subacute' mouse model of neurodegeneration therefore constitutes an attractive tool for mechanistic and interventional studies in excitotoxicity research. PMID- 8361622 TI - Sustained graded pain and hyperalgesia from harmless experimental tissue acidosis in human skin. AB - The present study was performed to decide whether tissue acidosis can induce sustained pain and, by that, possibly contribute to the pain in inflammation or ischaemia. A motorized syringe pump was used to infuse an isotonic phosphate buffer solution (pH 5.2) via sterile filter and cannula into the palmar forearm skin of human subjects (n = 6). This resulted in a localized burning pain sensation (edema and flare response) that was sustained as long as a constant flow was maintained. Flow rates between 1.2 and 12 ml/h were needed to reach individual pain ratings around 20% of a visual analogue scale (VAS). Increasing the flow in multiples of this basic rate led to approximately log-linear increases in individual pain ratings with reasonable congruence of the slopes. Stopping the pump or cooling the skin close to the cannula caused an abrupt pain relief. Prolonged infusion at flow rates producing pain ratings around 20% VAS led to localized changes in mechanical sensitivity: The touch threshold increased -as it did with control infusion of phosphate buffer at pH 7.4. However, the punctate force producing a threshold sensation of pain dropped from 64 to 5.7 mN (median values); the final level was usually reached within 15 min. In conclusion, experimental tissue acidosis provides a controllable and harmless method to produce sustained, graded and spatially restricted pain and hyperalgesia to mechanical stimulation. PMID- 8361623 TI - Ultrastructural study of Bunina bodies in the anterior horn neurons of patients with amyotrophic lateral sclerosis. AB - We ultrastructurally investigated Bunina bodies (BB) in the anterior horn neurons of 20 amyotrophic lateral sclerosis patients with BB. As for novel findings, filaments thicker than neurofilaments were not uncommonly observed inside the BB. They were occasionally observed around the periphery of the BB. Some of them were composed of bundles of filaments which appeared constricted at 40-50 nm intervals and were 20-25 nm in maximum width. Others consisted of bundles of unconstricted filaments measuring about 20-25 nm in diameter. The BB occasionally contained bundles of filaments of about 20 nm in diameter that closely resembled those found in ubiquitin-positive skein-like inclusions. It seems that some molecular disturbances such as ubiquitin play a role in the formation of the constricted and unconstricted filaments. Probably cytoskeletal or non-cytoskeletal proteins in anterior horn cells are damaged and accumulate to form aggregation of the filaments associated with BB. PMID- 8361625 TI - Regulation of the transcription factor c-JUN by nerve growth factor in adult sensory neurons. AB - We examined the regulation by nerve growth factor (NGF) of the immediate-early gene (proto-oncogene) c-jun in adult dorsal root ganglion (DRG) neurons using immunocytochemistry to c-JUN (the protein product of the proto-oncogene c-jun). Following a sciatic nerve crush, the injury-induced increase in c-JUN-like immunostaining was reduced in DRG neurons by continuous intrathecal infusion of NGF for one week. Conversely, in intact DRG neurons (i.e., without Wallerian degeneration), c-JUN-like immunoreactivity was markedly increased following four weeks of daily NGF antiserum injections (to remove target tissue-derived NGF) into the hindfoot. Taken together, these findings indicate that nerve transection (axotomy) results in a loss of target tissue-derived NGF leading to induction of the transcription factor c-jun which may play a role in axonal regeneration. PMID- 8361624 TI - Chondroitin sulfate proteoglycan form of cellular and cell-surface Alzheimer amyloid precursor. AB - The biological function of the amyloid precursor protein (APP) is still not fully understood. Recently, we reported that secreted truncated APP occurs in a chondroitin sulfate proteoglycan form. Here we present evidence that full length APP-chondroitin sulfate proteoglycan is present on the cell surface of C6 glioma cells. In addition, densitometric quantitation of Western blots showed that approximately 50% of the mature cell-associated full length APP is in the proteoglycan form. These findings suggest that the proteoglycan nature of APP may be important for the implementation of its biological function. PMID- 8361626 TI - Spatial re-arrangement of the vesicle apparatus in forebrain synapses of chicks 30 min after passive avoidance training. AB - A quantitative ultrastructural study of synapses was carried out in the forebrain IMHV (intermediate and medial hyperstriatum ventrale) of 1-day-old chicks 30 min after training to avoid pecking at a bead coated with methyl anthranilate. In 10 birds (5 control and 5 trained), the length, curvature and the number of the synaptic active zone profiles were measured, and the active zone profile length was observed to increase in trained chicks. The spatial arrangement of synaptic vesicles with respect to the active zone was examined using a statistical stereological approach. This showed that vesicles are not located uniformly but accumulate in two spatial pools which appear to rearrange following training, with a greater number of vesicles near the active zone. These data may reflect subtle changes in the functional efficacy of synapses in the IMHV in the initial phases of memory formation. PMID- 8361627 TI - Lipopolysaccharide induces fever and decreases tail flick latency in awake rats. AB - In humans, somatic aches and pains are frequently reported during fever. To determine whether exogenous pyrogen administration increases nociceptive responsiveness in rats, the tail flick reflex evoked by noxious heat was compared in animals that received an intraperitoneal injection of exogenous pyrogen (lipopolysaccharide) or vehicle (saline). There were no differences in skin temperature between lipopolysaccharide- and vehicle-injected rats. Awake rats injected with lipopolysaccharide exhibited an increase in colonic temperature and a decrease in tail flick latency when compared to vehicle-injected rats. Neural events that trigger fever may therefore also modulate nociceptive responsiveness. PMID- 8361628 TI - Ethanol dose-dependently attenuates NMDA-mediated thermal hyperalgesia in the rat. AB - Recent observations using acute and persistent pain models have suggested that activation of the N-methyl-D-aspartate (NMDA) receptor is required for mechanisms that underly the development and maintenance of thermal hyperalgesia. The present results document that both NMDA-mediated thermal hyperalgesia produced after acute intrathecal NMDA administration and NMDA-mediated thermal hyperalgesia produced in a model of neuropathic pain are dose-dependently and reversibly attenuated by intrathecal administration of ethanol (0.5-1.0%; total dose, 106 213 nmol, i.t.). This is consistent with recent reports that ethanol may function as a selective NMDA receptor antagonist at low concentrations and further extends the evidence that thermal hyperalgesia is mediated by NMDA receptors. PMID- 8361629 TI - Brain S-adenosylmethionine decarboxylase activity is increased in Alzheimer's disease. AB - We measured the activity of S-adenosylmethionine decarboxylase (SAMDC), a key regulatory enzyme of polyamine biosynthesis, in autopsied brain from 13 patients with Alzheimer's Disease (AD). As compared with the controls, mean enzyme activity was increased by 37-96% in all seven examined brain regions with statistically significant increases in temporal cortex (+96%), frontal cortex (+69%) and hippocampus (+90%). The elevated SAMDC may have occurred as part of a generalized polyamine response to brain injury, which has been previously described in experimental animal conditions. Above-normal SAMDC activity implies increased levels/metabolism of spermidine and spermine, two polyamines which are involved in neuronal regeneration, growth factor production, and activation of excitatory N-methyl-D-aspartate preferring glutamate receptors. Our data suggest the involvement of the polyamine system in the brain reparative and/or pathogenetic mechanisms of AD. PMID- 8361630 TI - Selective neurotoxicity of COOH-terminal fragments of the beta-amyloid precursor protein. AB - The primary component of amyloid deposits found in the brains of patients with Alzheimer's disease is the beta-amyloid protein, a derivative of a much larger precursor protein (beta PP). We have previously reported that overexpression of carboxyl (COOH)-terminal fragments of beta PP from an integrated DNA construct leads to degeneration of neuronally differentiating mouse embryonic stem cells and that the neuronal degeneration is related to approximately 14- and 15-kDa COOH-terminal fragments of the precursor protein. We here demonstrate that these putative cytotoxic fragments contain intact beta-amyloid protein. When such transformed cell lines are treated with dimethyl sulfoxide to induce differentiation into muscle cells, however, the resulting muscle cells remain viable (as do control non-transformed cells), despite the production of comparable amounts of the 14- and 15-kDa fragments. These results are consistent with the hypothesis that particular COOH-terminal fragments of beta PP are amyloidogenic and neurotoxic. PMID- 8361631 TI - The effects of aging on diurnal water intake and melatonin binding in the suprachiasmatic nucleus. AB - In vitro autoradiography was used to quantify [125I]melatonin binding in young rats and in aged rats that were screened for diurnal drinking prior to neurobiological study. Among the aged subjects studied, some rats exhibited a blunted diurnal rhythm in that a decreased percentage of water was consumed during the dark phase. Other aged animals maintained a strong nocturnal pattern of water intake similar to young rats. The density of [125I]melatonin binding in the suprachiasmatic nucleus (SCN) of the hypothalamus was significantly correlated with diurnal drinking, i.e. lower binding was associated with a more blunted rhythm. Thus, [125I]melatonin binding in the SCN may provide a marker for age-related decline in some aspects of biological functions. PMID- 8361632 TI - Expression of a TGF beta regulated, brain-specific mRNA in serum-free mouse embryo (SFME) cells. AB - The serum-free mouse embryo (SFME) cell line was isolated from 16-day-old Balb/c mouse embryos in medium in which the usual serum supplement to the culture medium was replaced by purified growth factors and other components. SFME is an unusual line that does not undergo senescence in vitro, maintains an apparently normal karyotype, and is growth inhibited by serum. Transforming growth factor beta (TGF beta) or calf serum induces expression of the astrocyte marker glial fibrillary acidic protein (GFAP) in these cells, and similar cells can be isolated directly from brain. By differential screening of a cDNA library derived from SFME cells, a calf serum- and TGF beta-regulated 8.5 kb mRNA was identified in SFME cells and the cDNA partially sequenced. This mRNA was detected only in RNA preparations from brain among a number of tissues examined, and may provide an additional marker of TGF beta-regulated differentiation in these cells. PMID- 8361634 TI - Chloramphenicol prevents carbachol-induced REM sleep in cats. AB - Twenty-four cats were implanted for chronic sleep recordings. One week after the surgery, cats were divided into four groups. Two groups were treated with three i.p. injections of 150 mg/kg chloramphenicol (CAP) separated by 12 h. Carbachol (8 micrograms/1 microliter) or saline (1 microliter) was injected into the pontine reticular formation (PRF) 1 h after the last injection of CAP. The other two groups received saline or carbachol into the PRF without CAP pre-treatment. Polygraphic recordings were started immediately after the microinjection and lasted 11 h. Carbachol increased REM sleep (P < 0.001) and reduced SWS2 (P < 0.05). In contrast, chloramphenicol reduced REM sleep (P < 0.001) and increased SWS2 (P < 0.01). The combination of these drugs increased wakefulness (P < 0.01) and reduced both SWS2 and REM sleep (P < 0.001). This data shows that chloramphenicol prevents carbachol induced REM sleep. Results are discussed in terms of an interaction between brain proteins and the cholinergic system to induce REM. PMID- 8361633 TI - Differential loss of dopamine D2 receptor mRNA isoforms during aging in Fischer 344 rats. AB - Effects of aging on the expression of dopamine D2 receptor isoforms (D2-long and short) in neostriatal subregions was examined by in situ hybridization histochemistry. Hybridization of a probe selective for the D2-long transcript was compared with signal generated by a probe recognizing both variants of D2 mRNA. Lateral quadrants of the neostriatum in old rats appeared to show declines in primarily the long transcripts. On the other hand, decreases in the expression of D2-short transcripts appeared to occur during aging in the ventromedial region of the striatum. These data suggest that the mechanisms involved in alternative splicing of D2 mRNA may be differentially altered in neostriatal subregions during aging. PMID- 8361635 TI - Changes in the neural cell adhesion molecule patterns on the rat glial cell surfaces with development and contact formation in vitro. AB - In monolayer cultures of newborn rat hippocampal cells, immunogold-labelling at the electron microscope level was used to study quantitatively the neural cell adhesion molecule (N-CAM) arrangement on the surface of glial soma and processes on 5 and 12 days in vitro (DIV). Four corresponding samples of micrographs were formed. To quantify the labelling, a stochastic geometry approach was used. Spectra of lateral distances between labels as well as simulated images of the surface label arrangement (invisible in micrographs) were derived and compared. The data show that, on both 5 and 12 DIV, N-CAM density on the surface of processes is approximately 2 times higher than that in somata; 12-DIV cells showing a lower (approximately 25%) N-CAM surface density as compared with the 5 DIV cells. This suggests that N-CAM expression in glia surfaces decreases while the cells form contacts, and N-CAM sorting between soma and processes remains stable. The simulated topographies of the lateral N-CAM arrangement might highlight fundamental mechanisms that underlie formation of the neural network. PMID- 8361636 TI - Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease. AB - Receptor autoradiography was used to quantify the number of dopamine D2 receptors labeled with [125I]epidepride in the medial temporal lobe of seven cases of Alzheimer's disease in comparison to eight cases of neurologically intact controls. The Alzheimer's disease cases showed the greatest losses of D2 receptors in the basolateral nucleus of the amygdala and molecular layer of the dentate gyrus and the smallest differences from controls in the perirhinal region and subiculum. The loss of D2 receptors in the hippocampus and amygdala of cases with Alzheimer's disease in concert with alterations in dopaminergic innervation could contribute to the clinical symptoms of this disorder. PMID- 8361637 TI - Area-dependent changes in GABAergic function after acute and chronic cold stress. AB - (1) The function of the gamma-aminobutyric acid (GABA)ergic system in certain areas of the rat brain was investigated after acute and chronic cold stress. (2) GABA concentration, [3H]GABA uptake and the activity of the synthesis enzyme glutamate decarboxylase (GAD) were measured. (3) Acute stress: (a) reduced GABA concentration in the corpus striatum (29%); (b) decreased GAD activity (under non saturating substrate concentration) in the olfactory bulbs (24%); (c) diminished neuronal uptake of [3H]GABA in the frontal cerebral cortex (65%), hypothalamus (86%) and olfactory bulbs (82%). (4) Chronic stress: (a) reduced the endogenous levels of GABA in the frontal cerebral cortex (51%), hypothalamus (26%) and olfactory bulbs (15%); (b) decreased GAD activity in the corpus striatum (32%) and olfactory bulbs (34%); (c) decreased neuronal uptake of [3H]GABA in the hypothalamus (83%). (5) These findings suggest that compensatory changes may develop in the GABAergic system after chronic stress. PMID- 8361638 TI - Iron uptake in the brain of the myelin-deficient rat. AB - The role of oligodendrocyte-derived transferrin in the transport and regional accumulation of iron has been studied in myelin-deficient (md) rats, which lack functional oligodendrocytes and have an almost complete depletion of transferrin in the brain, although they have normal peripheral levels of transferrin. The regional uptake of 59Fe into the brain has been studied autoradiographically in md and littermate control rats. Differences in uptake were found in only three of the 28 regions studied. These results suggest that the uptake and distribution of iron is not impaired in the md rat despite a markedly reduced level of brain transferrin. The choroid plexus contains high levels of transferrin mRNA and it is therefore likely that transferrin synthesized by choroid plexus epithelial cells can mediate the transport of iron within the brain. PMID- 8361639 TI - Partial hippocampal kindling increases paired-pulse facilitation and burst frequency in hippocampal CA1 neurons. AB - For up to 3 weeks after 15 evoked afterdischarges (partial kindling) in the hippocampus in vivo, paired-pulse facilitation of the CA1 apical dendritic excitatory postsynaptic potentials (EPSPs), recorded from single neurons in vitro, was significantly larger in neurons of kindled than control rats. Partial kindling did not significantly affect the resting membrane potential, the threshold or size of the action potential (AP), the fast afterhyperpolarization, input resistance, time constant or the EPSP threshold. The number of APs induced within the initial 20 ms of a long-duration 0.5-nA depolarizing current was significantly higher in the kindled than control neurons. The increase in paired pulse facilitation and intrinsic spiking in hippocampal CA1 after partial kindling may contribute to an increase in seizure susceptibility. PMID- 8361640 TI - Excitatory and inhibitory effects of 5-hydroxytryptamine on the firing rate of medial vestibular nucleus neurons in the rat. AB - The effects of microiontophoretic application of 5-hydroxytryptamine (5-HT) on the neuronal firing rate of the medial vestibular nucleus (MVN) were studied in anaesthetized rats. Ninety-three % of the units modified their background activity following 5-HT iontophoresis, enhancements of the firing rate being recorded in 42%, decreases in 38% and biphasic effects in 13%. 5-HT antagonists methysergide and ketanserin blocked the excitatory but not the inhibitory responses to 5-HT. These latter were, however, mimicked by 5-HT agonists 5 methoxy-N,N-dimethyltryptamine (5MeODMT) and 8-hydroxy-2(di-n-propyl amino)tetralin (8-OH-DPAT). It is concluded that 5-HT can variously influence the background activity of MVN neurons and that 5-HT2 and probably 5-HT1A receptors are involved in the responses. PMID- 8361641 TI - Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia. AB - The effects of hypoxia on protein kinase C (PKC) isozymes (alpha, beta I, beta II, and gamma) were examined in the hippocampus from rats subjected to hypoxic conditions (5% O2 in 95% N2) for 30 min in a chamber. Western blot analysis revealed that the total amounts of PKC-alpha (-26.0% of control) and -gamma ( 32.7% of control) were decreased significantly at the end of hypoxia, which was followed by the reduction of that of PKC-beta II (-23.7% of control at 7 days after hypoxia). Whereas, the PKC activities, which were measured by the incorporation of [gamma-32P] into a specific PKC substrate peptide, in both the cytosolic and the particulate fractions did not change. The reductions of PKC gamma and -alpha at the end of hypoxia may be related to the following neuronal degeneration. PMID- 8361642 TI - Cooling down to hibernate: sleep and hibernation constitute a physiological continuum of energy conservation. PMID- 8361643 TI - Deep and superficial noxious stimulation increases Fos-like immunoreactivity in different regions of the midbrain periaqueductal grey of the rat. AB - We have reported that the lateral region of the caudal third of the midbrain periaqueductal grey (PAG), which mediates flight and hypertension, receives inputs from lamina I and IIo and the lateral cervical nucleus (LCN) of the upper cervical spinal cord (UCC); whereas the ventrolateral PAG region, which mediates hypotension, quiescence and immobility, is targeted by cells in laminae VII, VIII and X. In the UCC the cells of laminae VII and VIII receive a significant afferent input from the deep neck muscles, whereas cells of laminae I and IIo and the LCN receive a large input from cutaneous nociceptors. Thus we investigated the hypothesis that nociceptive activation of the deep neck muscles would activate the spinal-ventrolateral PAG projection, whereas cutaneous nociceptive stimulation would activate the spinal-lateral PAG projection, by examining the expression of Fos protein. We found that deep noxious stimulation led to Fos positive cells predominantly in the ventrolateral PAG and superficial noxious stimulation led to Fos-positive cells predominantly in the lateral PAG. THE RESULTS: (i) indicate that the UCC afferent regulation of the PAG arises from topographically separable and functionally dissociable populations of neurons and (ii) raise the possibility that the ventrolateral and lateral PAG play important but different roles in mediating the distinctive affective, emotional and autonomic responses evoked by pain arising from deep or superficial structures. PMID- 8361644 TI - Distribution of corticotropin-releasing factor immunoreactive neurons in the brain of the tigerfrog, Rana tigrina. AB - The distribution of immunoreactive (ir) neurons containing corticotropin releasing factor (CRF) is described in the brain of the tigerfrog, Rana tigrina. The olfactory bulb, medial pallium, nucleus of the diagonal band of Broca and medial area of the amygdala of the telencephalon showed ir-CRF perikarya. The anterior and ventromedial thalamic nuclei, and the magnocellular nucleus preopticus (NPO) revealed several ir cells; a few NPO neurons were cerebrospinal fluid contacting in nature. The nucleus hypothalamicus ventromedialis contained a few cells, but the nucleus infundibularis ventralis of the infundibulum revealed several diffusely distributed perikarya. Individual ir-CRF perikarya were visualized in the optic tectum and interpeduncular nucleus. Extensive fiber terminals were present in the median eminence, but no fibers were discerned either in the neural lobe or in the pituitary gland. PMID- 8361645 TI - Target cells for the isthmo-optic fibers in the retina of the Japanese quail. AB - The isthmo-optic nucleus (ION) is the major origin of the centrifugal fibers projecting to the avian retina. The retinopetal fibers from the ION were labeled with biocytin and examined light- and electron-microscopically in the Japanese quail. The terminals were seen on cell bodies in the inner part of the inner nuclear layer. These neurons innervated with the isthmo-optic fibers appear to constitute a separate population different from the 'ordinary' amacrine cells. PMID- 8361646 TI - CSF and serum metabolic profile of patients with Huntington's chorea: a study by high resolution proton NMR spectroscopy and HPLC. AB - We studied both cerebrospinal fluid (CSF) and serum of 11 patients suffering from Huntington's disease (HD) and 12 control subjects by combining high resolution proton NMR spectroscopy and HPLC. NMR spectroscopy analysis of the CSF shows a significant increase (60%) in pyruvate concentration in HD patients. No unexpected molecules were detected. Glutamate, glutamine, aspartate, proline and GABA levels were found unchanged in the CSF of HD patients, using HPLC analysis. Conversely, a significant increase (30%) in the CSF level of glycine was detected. These observations are in agreement with the metabolic hypothesis of HD physiopathogenesis. In addition, the protocol combining NMR spectroscopy and HPLC provides a straightforward evaluation of brain metabolic status and blood-brain barrier function. PMID- 8361647 TI - Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures. AB - In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses. PMID- 8361648 TI - Topography of excitatory and inhibitory muscle responses evoked by transcranial magnetic stimulation in the human motor cortex. AB - Transcranial magnetic stimulation of the motor cortex produces a motor-evoked potential (MEP) in the electromyogram followed by a silent period (SP) which is thought to be due to cortical inhibition. In this study, the topography and size of the cortical areas from which an MEP and SP are evoked in the abductor pollicis brevis muscle (APB) of the hand were compared. The SP area was found to be large, encompassing and surrounding the MEP area. These findings infer the existence of an inhibitory surround limiting the excitatory area for APB in the human motor cortex. PMID- 8361649 TI - The upregulation of a glial cell surface antigen at the astrocytic scar in the rat. AB - The upregulation of a 106-kDa glial protein was examined using indirect immunohistochemical methods. The protein is recognized by the monoclonal antibody AMP1. Previous studies demonstrated that the AMP1 antigen is found on the external surface of cultured astrocytes and is involved in stabilizing adhesive interactions between these cells. In sections of injured adult rat brain, the spatial distribution of the AMP1 antigen correlated with the region of reactive gliosis. The relative intensity of immunofluorescence indicates that the AMP1 antigen is dramatically upregulated at the gliotic scar. The correlation between AMP1 antigen upregulation and reactive gliosis suggests that this molecule is critical to the process of CNS scar formation. PMID- 8361650 TI - Reduction of HSP70 and HSC70 mRNA inductions by bifemelane hydrochloride after transient ischemia in gerbil brain. AB - The effect of bifemelane hydrochloride (BFH) on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brain was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Following 3.5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The CA1 cells were almost lost by 7 days. Treatment with BFH twice before and after ischemia (total 60 mg/kg, i.p.) reduced the induction of HSP70 and HSC70 mRNAs both at 8 h and 1 day of the reperfusion, and about half of the CA1 cells survived at 7 days. Thus, the reduction of HSP70 and HSC70 mRNA inductions after ischemia may suggest that BFH reduced intra- and/or post-ischemic stress, and protected CA1 cells from ischemic damage. PMID- 8361651 TI - The Cystatin-C gene is not linked to early onset familial Alzheimer's disease. AB - The APP717 mutations discovered in only a few early onset Alzheimer's disease (AD) families have confirmed the genetic heterogeneity of this disorder. To identify the other gene(s) involved in the disease we selected the protease inhibitor, Cystatin-C, as a candidate gene. Cystatin-C is an amyloidogenic protein causing hereditary cerebral haemorrhage with amyloidosis-Icelandic type (HCHWA-I). It is localised with the beta-amyloid peptide in the arterial walls of AD brains. We have analysed the segregation of a polymorphic marker in this gene in 8 early onset AD families. Two early onset families showed clear non segregation of the marker with the disease. When the 8 families are analysed together (assuming only one other gene is involved), they present exclusion linkage criteria. These data indicate that Cystatin-C is not the site of the defect in 2 families and is not likely to be in the other families analysed. We conclude that the deposition of Cystatin-C in AD is a secondary event in the disease process, and that this gene is not pathogenic in familial AD. PMID- 8361652 TI - Band-pass filtering by voltage-dependent membrane in an insect photoreceptor. AB - The membrane properties of short type blowfly photoreceptors (R1-6) were investigated in dark and light adaptation with single electrode current and voltage clamp techniques. The impedance of the cells was defined in frequency domain by using discontinuous current clamp and white-noise-modulated current injection. We found that the slow activation and relaxation of the voltage dependent K+ conductance transform the photoreceptor membrane effectively into a band-pass filter. This behaviour could be observed under current clamp as voltage dependent outward and inward rectification of the membrane. The voltage-dependent band-pass filtering is likely to be present in all neurons with graded potentials and voltage-dependent membrane conductances. PMID- 8361653 TI - GABA- and glycine-like immunoreactivities in the cerebellum of the frog. AB - Immunocytochemistry was performed on consecutive semi-thin sections of frog cerebellum with antibodies raised against GABA and glycine. Somata of Purkinje cells and stellate cells were immunoreactive for GABA but not for glycine. In the granular layer some neurons were immunoreactive for GABA, fewer for glycine and even fewer for both GABA and glycine. Most of the GABA-positive neurons appear to be Golgi cells. Most of the glycine-positive neurons appear to be displaced cerebellar nucleus neurons. Compared with mammals true basket cells are missing, stellate cells are fewer in number and colocalization of GABA and glycine in Golgi neurons is encountered about ten times less often in the frog than in the rat. PMID- 8361654 TI - Corpus callosotomy effects on cerebral blood flow and evoked potentials (transcallosal diaschisis). AB - The role of the corpus callosum in diaschisis was examined through the acute effects of stereotactic corpus callosum section on cerebral blood flow and somatosensory or auditory evoked potentials bilaterally during unilateral brain retraction ischemia, using a previously reported swine model. Cerebral blood flow and evoked potential amplitude contralateral to retraction increased during retraction with the corpus callosum intact, compared with post-callosal section values. With retraction following callosal section, there was no increase in cerebral blood flow or evoked potential amplitude contralateral to retraction. Diaschisis during the early stages of a focal, unilateral injury takes the form of a contralateral disinhibition (as measured by cerebral blood flow and evoked potentials), an effect which is lost following callosal section. PMID- 8361655 TI - Changes in parvalbumin-immunoreactive neurons in the rat hippocampus following a kainic acid lesion. AB - Changes in a sub-population of hippocampal non-pyramidal neurons following a unilateral lesion with kainic acid were examined using an antibody raised against the Ca-binding protein parvalbumin. A loss of 71-97% of the parvalbumin immunoreactive neurons occurred at the three post-lesion times studied (1, 2 and 4 weeks) in all areas of the ipsilateral hippocampus, but no such loss was observed in the dentate gyrus. Resistant parvalbumin-immunoreactive neurons occurred principally in stratum pyramidale and displayed altered morphology from the normal with swollen dendrites and dendritic varicosities. The contralateral hippocampus exhibited losses of parvalbumin-immunoreactive cells, but this was restricted to stratum oriens of CA1. This data demonstrates the loss of a specific and important population of non-pyramidal neurons which might be responsible for the chronic loss of functional inhibition seen in this animal model of temporal lobe epilepsy. PMID- 8361656 TI - Unique properties of norepinephrine release from terminals arising from the locus coeruleus: high potassium sensitivity and lack of linopirdine (DuP 996) enhancement. AB - The dose-response of K+ to elicit the release of norepinephrine (NE), acetylcholine (ACh), dopamine (DA) and serotonin (5-HT) from rat brain slices was examined. Cerebral cortical and hippocampal [3H]NE release had steeper K+ dose response curves than those observed for apparent hippocampal [3H]ACh, striatal [3H]DA and striatal [3H]5-HT release. In contrast, the apparent release of [3H]NE from the hypothalamus had a K+ dose-response curve similar to those observed for the release of [3H]ACh, [3H]DA and [3H]5-HT. Linopirdine, a drug which enhances K(+)-stimulated release of [3H]Ach, [3H]DA and [3H]5-HT, had no effect on cerebral cortical [3H]NE release even at submaximal K+ stimulation. Hippocampal [3H]NE release was also not affected by linopirdine, however the compound significantly enhanced K(+)-evoked [3H]NE release from hypothalamic slices. These data point to unique properties of [3H]NE release from terminals arising from the locus coeruleus (i.e. those found in the cerebral cortex and hippocampus) when compared to [3H]NE release from terminals derived from the lateral tegmentum (i.e. those found in the hypothalamus) and the release properties of other neurotransmitters. The relative high K+ sensitivity of NE release from coerulear terminals may be related to the lack of linopirdine effects on cerebral cortical and hippocampal [3H]NE release. PMID- 8361657 TI - Glucocorticoid modulation of neurotrophin expression in immortalized mouse hippocampal neurons. AB - To see whether glucocorticoid hormones can influence the regulation of neurotrophin expression in hippocampal neurons, we have used reverse transcription followed by polymerase chain reaction to investigate changes in the mRNA levels of nerve growth factor (NGF) and neurotrophin-3 (NT-3) in immortalized hippocampal neurons after dexamethasone application. Our results show that NGF mRNA levels rise in both embryonic and postnatal neurons, but with different time courses, while NT-3 levels rise in the embryonic but not in the postnatally derived cell line. Modulation of NT expression by glucocorticoids may therefore be developmentally regulated. PMID- 8361659 TI - Mutant mouse cerebellum does not provide specific signals for the selective migration and development of transplanted Purkinje cells. AB - Embryonic cerebellum transplanted to adult Purkinje cell degenerate mice was assessed for integration and Purkinje cell migration by using the antigenic markers Thy-1 and Leu-4. It was found that the grafted cells migrated into the host's molecular layer, but there was no evidence for specific migration of Purkinje cells. Furthermore, grafted cells were found to form normal cerebellar cyto-architecture only with other grafted cells and not with the host's cells. PMID- 8361658 TI - Voltage-dependent K+ currents in guinea pig Muller (glia) cells show different sensitivities to blockade by Ba2+. AB - The effect of externally applied Ba2+ and Na+ on K+ currents was investigated by means of whole-cell patch-clamp in isolated and in situ Muller cells from guinea pig retina. Muller cells express a typical set of K+ currents, i.e. an ohmic current, an inactivating inward current (IK(IR)), a delayed rectifier (IK(DR)) and an inactivating outward current (IK(A)). Inactivation of the inward current did not occur when extracellular Na+ was replaced by choline. When administered in increasing concentrations, Ba2+ blocked these K+ currents in a typical sequence: the ohmic current and IK(A) were most sensitive, followed by IK(IR), whereas IK(DR) was not completely blocked even in 1 mM Ba2+. The differential sensitivity of Muller cell K+ currents to external Ba2+ may be a tool which can be used to improve our understanding of the Muller cell response to physiological stimulation of the retina. PMID- 8361660 TI - The inhibition by indoleamines (tryptamine and serotonin) of ocular serotonin-N acetyltransferase from Rana perezi is temperature-dependent. AB - Temperature effects on ocular serotonin N-acetyltransferase (NAT) kinetics characteristics from Rana perezi have been studied with respect to tryptamine and serotonin as substrates. Monoamine oxidase (MAO) activity does not interfere in NAT assay at acceptoramine concentrations used in NAT kinetics characterization from R. perezi retina. NAT shows an inhibition by high substrate (serotonin) concentration, which is temperature-dependent. NAT follows the Michaelis-Menten equation at low temperature, whereas at high temperatures (> 10 degrees C) an inhibition by serotonin is observed. This inhibition of NAT activity by serotonin could act as an amplification mechanism to increase daily melatonin rhythm amplitude in the retina of ectotherms. PMID- 8361661 TI - Gamma-L-glutamyl-L-glutamate is an endogenous dipeptide in the rat olfactory bulb which activates N-methyl-D-aspartate receptors. AB - The concentration of gamma-L-glutamyl-L-glutamate (gamma-glu-glu), a potent displacer of excitatory amino acid receptor binding, and other structurally related dipeptides were determined in extracts of the rat olfactory bulb by a novel liquid chromatographic method. Whole-cell patch clamp recordings of currents from freshly isolated neurons showed that gamma-glu-glu produced inward currents at negative holding potentials, provided microM concentrations of glycine were added and no Mg(2+)-ions were present, indicating activation of N methyl-D-aspartate receptors. Consistently, geometry optimization of gamma-glu glu using molecular mechanics calculations, suggested a bent conformer with structural features supporting this view. PMID- 8361662 TI - Delayed histologic damage and neuron death in the substantia nigra reticulata following transient forebrain ischemia depends on the extent of initial striatal injury. AB - Transient forebrain ischemia in normoglycemic, normotensive rodents reproducibly causes selectively vulnerable neurons in the striatum to degenerate within 24 h. Neurons in the substantia nigra reticulata (SNR) are resistant to this acute process. Histologic evidence demonstrates that the combination of acute ischemic injury to the caudate nucleus and globus pallidus is associated with delayed neuron degeneration in the SNR that matures at 3 weeks after reperfusion. Ischemia, like certain ablative neurotoxin lesions, may provoke degenerative, perhaps transneuronal events that continue to evolve long after the initial insult. PMID- 8361663 TI - Dystrophin and dystrophin-related protein expression in Torpedo marmorata electric organ. AB - The presence of different dystrophin-related protein forms was investigated in electric organ as compared to cardiac, white or red skeletal muscles from Torpedo marmorata. Two strategies were followed. First, we used specific C-terminal dystrophin and dystrophin-related protein monoclonal antibodies which we characterized in the present study. 400 kDa protein bands were detected in the tissues mentioned above with both specific types of antibodies. Second, we produced monoclonal antibodies raised against a dystrophin-enriched preparation from T. marmorata electric organ. Western blot and immunofluorescence analyses showed the tissue specificity of T. marmorata antibodies and allowed us to classify them as types I, II and III. Vessel walls and neuromuscular junctions were labeled with T. marmorata type II and III antibodies in human muscles (skeletal and smooth). Both approaches demonstrated that the T. marmorata electric organ contained different proteins related with dystrophin: a dystrophin form, a dystrophin-related protein form and a dystrophin-related protein isoform, homologous to the dystrophin-related protein present in muscle vessel walls and at the neuromuscular junctions of human tissues. The presence of dystrophin and dystrophin-related protein is finally discussed relative to their functions and organ specificities. PMID- 8361664 TI - Alternative splicing of the mRNA encoding the alpha subunits of the G(o) GTP binding protein during brain development and in neuronal cell lines. AB - The RNA encoding the alpha subunit of the G(o) GTP-binding protein is alternatively spliced in some tissues to produce mRNAs encoding two distinct forms of the protein which differ at the carboxyl terminus. This alternative splicing process is observed at all stages during development of the rat brain and heart and in some but not all neuronal cell lines. These effects are discussed both in terms of the regulation of the alternative splicing event and the functional role(s) of the two forms of the protein which it produces. PMID- 8361665 TI - Electrophysiological changes in the surrounding brain tissue of photochemically induced cortical infarcts in the rat. AB - Small infarctions in the parietal cortex of Wistar rats were produced photochemically using the Rose Bengal technique. The infarctions evoked reproducible cortical lesions of about 2 mm diameter. In the surrounding brain tissue changes in electrophysiological responses occurred. Whereas in control animals a paired-pulse inhibition could be evoked all over the neocortex, in infarcted animals the paired-pulse inhibition was significantly reduced or even absent within an area extending up to 5 mm lateral from the lesion center. The changes in paired-pulse inhibition were already present on the first day and persisted at least up to 60 days after infarction. These functional changes may contribute to neurological deficits occurring after cerebral infarcts. PMID- 8361666 TI - The preconditioned hippocampus accelerates HSP70 heat shock gene expression following transient ischemia in the gerbil. AB - To evaluate the mechanism of tolerance for ischemia, inductions of heat shock protein (HSP) 70 mRNA and immunoreactive HSP70 protein were studied in the preconditioned gerbil hippocampus. Following the single 3.5-min ischemia, HSP70 mRNA was induced in all hippocampal cells. However, the hippocampal CA1 cells produced only a minimum HSP70 protein, and the cells were almost lost by 7 days. Following the 3.5-min ischemia after 2-min pretreatment, the CA1 cells produced a strong immunoreactive HSP70 signal and large populations of the CA1 cells survived at 7 days. The peak time of the HSP70 mRNA induction shifted to earlier period of reperfusion in the CA1 cells as compared to the case with single ischemia. This accelerated change of HSP70 expression could play an important role for the acquisition of ischemic tolerance of the hippocampal CA1 neurons. PMID- 8361667 TI - Functional evidence for a L-AP3-sensitive metabotropic receptor different from glutamate metabotropic receptor mGluR1. AB - The efficacy of mGluR agonists quisqualate and 1S,3R-aminocyclopentane-1,3 dicarboxylic acid (1S,3R-ACPD) in stimulating the inositol phosphate (IP) formation in primary cultures of cerebellar granule neurons correlated with mGluR1 mRNA expression and was affected by the medium KCl content. L-2-Amino-3 phosphonopropionic acid (L-AP3) mimicked the stimulatory action of mGluR agonists. Maximal stimulatory doses of mGluR agonist 1S,3R-ACPD and L-AP3 were additive, suggesting the action of L-AP3 on a receptor different from mGluR1. Indeed, in embryonic kidney 293 cells transfected with mGluR1 cDNA quisqualate and 1S,3R-ACPD but not L-AP3 stimulated the IP formation. PMID- 8361668 TI - Early and transient effects of neutron irradiation on dopamine receptors in the adult rat brain. AB - The early neurochemical effects of neutron-gamma radiation exposures were studied through ligand dopamine D1, D2 receptors binding experiments. The parameters of binding were investigated on crude preparations from striatum at different delays (from 2 to 72 hours) after irradiation. An early and transient increase in the total number of sites was seen after exposure, even at infra-lethal dose. This 'radiosensitivity' was higher for D1 than for D2 receptor. It is assumed that these modifications could participate in the early neuro-vegetative syndrome observed in irradiated persons. PMID- 8361669 TI - The rat nucleus accumbens: two levels of complexity in the distribution of glutamic acid decarboxylase (67 kDa) and preproenkephalin messenger RNA. AB - The distribution of messenger RNAs (mRNAs) encoding the 67 kDa isoform of glutamic acid decarboxylase (GAD67), a rate-limiting enzyme in the biosynthesis of gamma-aminobutyric acid, and preproenkephalin (PPE), the precursor of enkephalin, was analysed in the rat nucleus accumbens (NAS) taking in account its compartmentation in 'core' (NAS(core)) and 'shell' (NASshell). While GAD67 mRNA levels were more abundant (+48%) in NASshell than in NAS(core), hybridization signals for PPE mRNA were mainly found in NAScore. At a cellular level, hybridization signals for GAD67 mRNA were present in 75% and 80% of neurons NASshell and NAS(core), respectively. The level of GAD67 mRNA found higher in the NASshell corresponds in fact to a greater density of neurons in NASshell than in the NAS(core). The hybridization signals for PPE mRNA were observed in very few neurons of NASshell and in around half of the neurons in NAS(core). Besides this medio to lateral difference, GAD67 and PPE mRNAs were distributed in NAS(core) according to a rostro-caudal gradient, the content of both mRNAs being higher in the rostral part than the caudal part of this area. PMID- 8361670 TI - Prenatal D1, D1b and D3 dopamine receptor gene expression in the rat forebrain: detection by reverse polymerase chain reaction. AB - Three dopamine receptor mRNAs were detected by reverse polymerase chain reaction in the rat forebrain during ontogeny. The D1 receptor mRNA gave a faint signal from gestational day 11 (G11) on, while the D1b receptor was not detectable before G12. The D3 receptor mRNA was slightly expressed at G11 and clearly present at G14. Our results show that these mRNAs are present at early stages of fetal life, each one with its specific time of appearance. PMID- 8361671 TI - Morphometric characterization of the arcuate nucleus neurons of the rat. A Golgi study. AB - Six types of neurons were identified and characterized by the Golgi technique in the hypothalamic arcuate nucleus of the rat: non-ramified unipolar, ramified unipolar, non-ramified bipolar, ramified bipolar, small multipolar, and large multipolar. All had few spines, both somatic and dendritic spines. Characterization of the neuronal cytoarchitecture of the arcuate nucleus could be useful in developmental studies under specific experimental conditions. PMID- 8361672 TI - Effect of aluminum chloride, -citrate, and -maltol on the calcium-mediated degradation of neurofilament proteins. AB - Aluminum (Al) has been observed to cause neurofilament protein accumulation in both experimental animals and cultured cells. Impairment of axonal transport is thought to be a mechanism of toxicity. Inhibition of the degradation of neurofilament proteins, however, resulting in accumulation of these proteins may be an alternative mechanism for Al toxicity. In the present study, the effect of calcium (Ca) on the proteolysis of the neurofilament triplet proteins by calcium activated neutral proteases (CANP) was studied in the isolated sciatic nerve explants. The extent of the degradation was found to be dependent on the Ca concentration. The effect of Al chloride, -citrate and -maltol on the calcium induced degradation was studied. No effect of any of the Al compounds was observed, suggesting that the metal may exert its neurotoxic effect via a mechanism other than impairment of neurofilament proteolysis. Maltol itself was found to enhance the effect of Ca on the degradation of neurofilament proteins, probably by facilitating the movement of Ca across the neuronal membrane. PMID- 8361673 TI - Workshop on the X-ray fluorescence of lead in bone: conclusions, recommendations and summary. AB - A workshop on the use of X-ray fluorescence (XRF) to noninvasively measure lead in bone was convened by the National Institutes of Environmental Health Sciences (NIEHS) and the Environmental Health Sciences Center of the Mount Sinai School of Medicine. The impetus for the workshop stemmed partly from NIEHS' concern that XRF machines produced for this purpose are licensed by the Food and Drug Administration as research devices, a designation that indicates they are safe to use on people but says nothing about the precision and accuracy of the data they generate. Therefore, a major purpose of the workshop was to scientifically examine these issues in a multi-disciplinary setting, to explore the current status of XRF research employing two different XRF techniques for lead-bone measurements: K-shell and L-shell XRF spectroscopy (K-XRF, L-XRF) and to make recommendations for future research in these techniques. PMID- 8361674 TI - Cocaine cytotoxicity in serum-free environment: C6 glioma cell culture. AB - Rat glioma C6 cells were employed to determine the vulnerability of the CNS derived cells to cocaine. The cells were cultured either in the presence of serum or in serum-free (defined) medium to model glial development in the normal brain. In serum-containing medium, cocaine in amounts up to 100 micrograms/ml neither retarded cell proliferation nor altered cell morphology. In the absence of serum, the culture growth was profoundly retarded and cell death was observed with amounts as small as 0.1 micrograms/ml. Even brief (24 hrs) exposure to low cocaine concentrations in serum-free medium irreversibly decreased the cell number. However, an initial 24 hr exposure to 0.1-2.5 micrograms/ml cocaine prolonged survival of cells subsequently exposed to a lethal concentration (100 micrograms/ml). Benzoylecgonine in amounts up to 100 micrograms/ml had no effect on cell proliferation, with or without serum. These data show that cocaine in the absence of serum is highly cytotoxic, which indicates a possibility that the blood-brain-barrier-protected CNS cells may be particularly vulnerable to the drug when it enters the nervous system. PMID- 8361675 TI - Sex-related spatial learning differences after prenatal cocaine exposure in the young adult rat. AB - Prenatal cocaine exposure in humans is associated with a variety of adverse neurobehavioral effects. In the rat, in utero cocaine exposure has been shown to elicit learning impairment during early postnatal development. However, little research has focused on the persistence of these behavioral disruptions. The current study examines the long-term effects of prenatal cocaine exposure on learning performance during young adulthood. Fetal cocaine exposure evoked differential effects in male and female rats on radial-arm maze learning performance. Cocaine-treated females showed significantly impaired choice accuracy during acquisition of radial-arm maze performance when compared to control females. In contrast, cocaine-treated males showed no impairment and in fact showed significantly improved performance on one measure of choice accuracy. For both sexes, this effect was apparent during the final third of acquisition. No evidence was found to suggest altered sensitivity to anticholinergic drugs. While both nicotinic and muscarinic cholinergic antagonists caused significant impairments in memory performance, control and cocaine-exposed rats were effected equally. Single doses of these drugs which caused moderate memory deficits were chosen for use in the current study. The entire dose range should be evaluated to determine the relative sensitivity of cocaine-exposed and control animals to these drugs. The results of this study indicate that there are cognitive effects of prenatal cocaine exposure which persist into adulthood and the sex of the offspring seems to be critical. PMID- 8361676 TI - Age-related susceptibility to MPTP-induced neurotoxicity in mice. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause neurotoxicity in rodents and nonhuman primates. In this study the ontogeny of MPTP-induced DA depletion and formation of reactive oxygen species (ROS) were evaluated in mouse striatum. C57/B6N mice were injected four times with 0 or 10 mg/kg MPTP (i.p.) at two-hour intervals on either postnatal day 23, at about 7 months of age, and at one year of age. Animals were sacrificed 1, 2, 4, 8, 12, 24, 48 and 72 hours after the last dose. Brains were rapidly removed and striata were dissected for neurochemical analysis. Dopamine (DA) and its metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured by HPLC/EC. ROS formation was measured by a fluorescence probe, 2',7' dichlorofluorescein-diacetate (DCFH-DA). MPTP produced a slight but significant decrease of DA only 4 hours post dosing on PND 23. DOPAC and HVA levels decreased up to 4 and 8 hours post dosing respectively and returned to control values thereafter. At 7 months of age, MPTP produced a 50-65% decrease of DA and its metabolites (DOPAC and HVA) in striatum 24 hours post dosing. In one year old mice, MPTP produced an 80% decrease of DA and 60-80% decrease of DOPAC and HVA in striatum. In contrast, ROS formation in striatum was not significantly increased by MPTP treatment at any age but was decreased at 1 hour only in PND 23 and 7 month old mice. These studies suggest that MPTP-induced neurotoxicity is age dependent in the mouse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361677 TI - The role of the septohippocampal pathway in the mediation of colchicine-induced compensatory changes in the rat hippocampus. AB - To study the involvement of the septohippocampal pathway in colchicine-induced changes in the hippocampus, colchicine was used to lesion the septum and/or hippocampus of male, Fischer-344 rats. Rats were killed 12 weeks post-lesion and histochemical and biochemical measurements were performed. [3H]-QNB binding, choline acetyltransferase (ChAT) activity and agonist-stimulated release of inositol phosphates (IPs) were measured in hippocampal slices. AChE histochemistry was also performed to visualize AChE positive fibers in the hippocampus. Increases in ChAT activity, AChE staining and carbachol-stimulated IP release observed in hippocampal-lesioned animals were attenuated in animals receiving both septal and hippocampal lesions. However, the decrease observed in [3H]-QNB binding sites after intradentate colchicine was not affected by septal lesions. Subsequent studies also found enhanced sensitivity to excitatory amino acid (EAA)-stimulated IP release in hippocampal-lesioned animals. Similar to the changes observed in carbachol-stimulated PI hydrolysis, this increase was also long-lasting. However, the hyperstimulation of EAA-induced IP release was not attenuated by the septal lesion. Thus, it appears that the neurochemical and morphological changes observed in the hippocampus following intradentate colchicine are dependent upon more than one afferent projection to the hippocampus. PMID- 8361678 TI - Neurobehavioural effects on workers in a video tape manufacturing factory in Singapore. AB - This study was carried out in a video tape manufacturing factory in Singapore where workers were exposed to mixed solvents consisting of methyl ethyl ketone (MEK), cyclohexanone (CHE), tetrahydrofuran (THF), and toluene (TOL). The objectives were to quantify workers' exposure to the various solvents and to evaluate if there were any neurobehavioural changes among the workers compared to controls. Nineteen exposed workers out of the workforce of forty-five were studied. Twenty-six workers (with no exposure) matched for ethnic group, age, and years of education served as controls. Eight-hour personal environmental samples were analyzed for the 19 workers along with symptom questionnaires, clinical examinations, and neurobehavioural tests including the Santa Ana Dexterity, Finger Tapping, Digit Span, and Visual Reproduction tests. The mean TWA concentrations for MEK, THF, CHE, and TOL were all below the current American Conference of Governmental Industrial Hygienists Threshold Limit Values (TLV). However, the total solvents concentration index exceed unity in one of the work areas. Significant differences were observed for prevalence of headache, and eyes and nose irritation among the exposed workers. There were also significant differences for the Santa Ana test for both-hands, Digit Span test and Visual Reproduction test. However, no dose-effect relation between behavioral scores and airborne solvent exposure was noted. The study suggests that solvent-exposed workers in video tape manufacturing plants may have poorer visual motor control and recent memory impairment (visual and verbal) than unexposed workers. Dermal absorption of solvents may have played a role in these results by increasing workers exposure. PMID- 8361679 TI - Microchromatographic analysis of lipids, protein, and occurrence of lipid peroxidation in various brain areas of vanadium exposed rats: a possible mechanism of vanadium neurotoxicity. AB - Administration of sodium metavanadate (3 mg/kg) to adult female Sprague Dawley rats for 5 consecutive days by intreaeritoneal route resulted in major alterations in lipid profiles and protein concentration in all the brain regions. Sodium metavanadate exposure displayed phospholipids, cholesterol and cerebrosides, and protein, but ganglioside concentration was significantly increased in various areas of the brain. Loss of body weight observed in this study could be attributed to the loss of appetite; loss of nutrients and wasting of tissues. It is likely that large amount of body water was lost through diarrhoea. Gas liquid chromatography has revealed that oleic acid, linoleic acid, linolenic acid, and archidonic acid were preferentially lost in the brain of vanadium-exposed rats. Thin layer chromatography further proved degradation of individual lipids. Sphingomyelin was substantially decreased followed by phosphatidyl choline and phosphatidyl ethanolamine, but phosphatidyl serine and phosphatidyl inositol were slightly affected. Our recent work has demonstrated vanadium-induced stimulation of lipid peroxidation in the various regions of the rat brain. It is speculative that deterioration of myelin sheath by vanadium exposure contributed to preferential lipid loss but lesser loss of protein. These studies also indicate that vanadium-induced stimulation of lipid peroxidation is characterized by a selective loss of brain polyunsaturated fatty acids and thus comprehensive degradation of lipids in the different regions of the rat brain. However, the mechanism involved in the elevation of ganglioside levels is not yet fully understood. It is concluded that these perturbations produced damage to the associated physiological functions leading to CNS dysfunctions. PMID- 8361680 TI - Short-term, preweaning treatment with tetracycline affects physical development and behavior in rats. AB - Tetracycline (TC) was administered indirectly to rat pups through maternal milk, giving mothers diluted TC solutions as a single source of drinking water, during 13-16 days of postnatal age (PND) in Experiment 1. In Experiment 2, using rats of a different strain, TC dose and its application period were reduced from 0.5 mg/ml to 0.25 mg/ml and from PND 13-16 to PND 13-15, respectively. In Experiment 3, TC was administered directly to the pups via stomach intubation during PND 13 16. The effects of these short-term treatments were tested in adulthood. Brain weight decreased, although no abnormal changes were found histologically in the cerebral cortex. Immobility time in the forced swimming test was decreased more in the TC group as compared to the controls. These results suggest that even a small amount of TC could affect physiological development and behavior. In Experiment 4, mothers were given TC in their drinking water (0.5 mg/ml) for 1 to 5 days, beginning on PND 12. On each of the treatment days, measurements were made of the weight of brain and body, and of the concentration of TC in the brain and in gastric curd of offspring. The greater the TC intake by dams was, the more remarkable was the decrease in the brain weight of offspring. TC concentration of gastric curd was on the order of 1-3.5 micrograms/g curd. PMID- 8361681 TI - Morphological alterations of neurons and astrocytes in guinea pigs exposed to low levels of inorganic lead. AB - Both astrocytes and neurons potentially undergo structural and functional alterations in the brains of animals exposed to low levels of lead (Pb). No morphometric studies of astrocytes have been reported to date in animals in low Pb exposure. In the present study, morphometric measurements of astrocytes and pyramidal neurons in the frontoparietal cortex were made in guinea pigs exposed postnatally (5 or 10 days) or prenatally (gestational day 22 to birth) to low Pb levels. Although few significant effects of Pb treatment were detected by the rigorous statistical model applied, a recurring trend was noted for postnatal Pb treatment to increase astrocyte maximum diameter (dmax). In addition, prenatal Pb treatment was associated with increased apical and basal dendritic length, increased total apical dendrites per cell and an increased basal branching complexity in neurons. PMID- 8361682 TI - Effect of L-dopa on copper concentrations in the rat brain. PMID- 8361683 TI - Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. PMID- 8361684 TI - Quantitative studies on aluminum deposition and its effects on neurofilament protein expression and phosphorylation, following the intraventricular administration of aluminum maltolate to adult rabbits. AB - The deposition of aluminum (Al) in the brain and spinal cord of adult male New Zealand white rabbits was monitored following the intraventricular administration of Al maltolate. Although decreasing concentrations of Al were observed from the injection site (approximately 10 micrograms/g dry tissue) to the lumbar cord (2.1 micrograms/g), argyrophilic tangles were present in the perikarya and proximal neurites of neurons as far distal as the lumbar and sacral cord areas. Quantitative immunoblot studies of the three neurofilament protein isoforms failed to detect changes resulting from Al maltolate treatment. Similarly no significant alterations in the total phosphate content of these cytoskeletal proteins were observed. Lastly, on Northern blots, the expression of genes encoding for the 200 kDa and 68 kDa neurofilament proteins also was unaffected by Al maltolate treatment. PMID- 8361685 TI - Mrs. Nelson's cabin. PMID- 8361686 TI - Myths & facts ... about lead poisoning. PMID- 8361687 TI - Documentation do's and dont's. PMID- 8361689 TI - Am I doing enough? PMID- 8361688 TI - How to apply a transdermal drug patch. PMID- 8361690 TI - Managing chest drainage problems. PMID- 8361691 TI - Managing the modern care plan. PMID- 8361692 TI - Treating a jellyfish sting. PMID- 8361694 TI - Points worth hearing. PMID- 8361693 TI - Beat the clock: saving the heart with thrombolytic drugs. PMID- 8361695 TI - Blood glucose: the right levels. PMID- 8361696 TI - Why was Lois so demanding? PMID- 8361697 TI - Exposing late allergies. PMID- 8361698 TI - "Hey nurse ... thanks". PMID- 8361699 TI - Pediatric hospice nursing: making the most of each moment. PMID- 8361700 TI - Understanding neurovascular assessment. PMID- 8361701 TI - Diabetes update 93. PMID- 8361702 TI - Delirium in the elderly. PMID- 8361703 TI - Endoscopic thoracotomy: how it can spare patients from major thoracic surgery. PMID- 8361704 TI - AIDS update: caring for patients with diarrhea. PMID- 8361705 TI - One nurse's lesson. PMID- 8361706 TI - Teaching a patient to perform Kegel exercises. PMID- 8361708 TI - Norms and nursing science: a question of values. PMID- 8361707 TI - Nursing and medicine: two different disciplines. PMID- 8361709 TI - Changing family patterns and health. PMID- 8361710 TI - Nursing centers without nursing frameworks: what's wrong with this picture? PMID- 8361711 TI - The adequacy and scope of Roy's adaptation model to guide cross-cultural pain research. AB - The purpose of this study was to examine the adequacy (operational, empirical, and pragmatic) and scope of the Roy adaptation model and the gate control theory of pain to guide the cross-cultural study of pain. The sample consisted of 60 Mexican-American and Anglo-American women undergoing elective cholecystectomy. The conceptual-theoretical-empirical structure developed by Fawcett and Downs (1986) provided the framework for designing the study. Operational adequacy was determined by examining the reliability and validity of the empirical indicators used; it was judged adequate. Empirical adequacy was evaluated by comparing empirical data to hypothesized expectations. Only some of the conceptual theoretical relational statements were supported. Pragmatic adequacy was assessed by determining whether innovative practice strategies might be derived from the data; several were recommended. Finally, the scope was determined by examining the variables identified by the model and several additional variables. Scope was judged adequate to the current stage of the model's development. PMID- 8361712 TI - The lived experience of grieving the loss of an important other. AB - The purpose of this study was to uncover the structure of the lived experience of grieving the loss of an important other using Parse's research methodology. Parse's theory of human becoming provided the nursing perspective for the study. Five participants described their experience of grieving the loss of an important other through dialogical engagement with the researcher. The researcher dwelled with the transcribed descriptions and through the processes of extraction synthesis uncovered the structure of the lived experience of grieving the loss of an important other as an anguished suffering in devastating void amidst consoling movements away from and together with the lost one and others while confidently moving beyond personal doubts. Linked to the major concepts of Parse's theory through heuristic interpretation, the structure was abstracted as valuing the connecting-separating in transforming. The study adds to knowledge about grieving and expands Parse's theory of nursing. Recommendations for practice and further research are offered. PMID- 8361713 TI - Recovering in depressed women: research with Peplau's theory. AB - The purpose of this research was to describe the process of recovering in women who have been depressed. The descriptive research design for this study was guided by Peplau's interpersonal theory of nursing. The sample consisted of seven women who had at one time been hospitalized with a diagnosis of depression and who now considered themselves to be recovering. Audiotaped interviews were conducted in the women's homes. Verbatim transcripts were analyzed using content analysis. The analysis revealed that the process of recovering as described by the seven depressed women consisted of eight categories which comprised three phases. Recovering was initiated by a crisis or turning point experience. Phase I consists of the turning point and professional support; phase II consists of determination, work-over-time, support of family and friends, and successes; and phase III consists of self-esteem and maintaining balance. The process of recovering is internal and ongoing. Further research is suggested. PMID- 8361714 TI - Health for people with a terminal diagnosis. AB - A naturalistic study was designed to investigate how people with terminal diseases describe health. Three domains emerged. The mental/emotional domain included hope, love, and control. The spiritual domain contained belief in a higher power, recognition of mortality, and self-actualization. The physical domain consisted of health promotion activities, feeling good, and relationship with a physician. This investigation suggested many similarities with Newman's model. One area of agreement was in the informants' belief that their disease was a part of their health. The emergence of the disease pattern allowed health to unfold. Many informants believed they became healthier because of their diagnoses. PMID- 8361715 TI - How to develop a teaching plan that integrates IVD. PMID- 8361716 TI - Lifting weights. AB - As with engineering improvements, many administrative changes can reduce back injuries. The following administrative steps are recommended: Training for all employees. Increase awareness with posters and meetings. Notify suppliers of reduced weight limit. Job rotation for heavy lifting jobs. Proper maintenance and housekeeping. Use back belts when necessary. Some recommendations should enable employers to begin implementing changes immediately. Other suggestions will require time and money but are worth the investment. PMID- 8361717 TI - Heat protection. Garments may shield from burns but heat can attack inside out. PMID- 8361718 TI - Oral medicine as a specialty. PMID- 8361719 TI - Unusual progression of impacted third molars. PMID- 8361720 TI - Third molars as an acute problem in Finnish university students. AB - The study was carried out to determine the risk of acute disease of third molars in young adult patients. The subjects in this case-control study were 100 consecutive university students who complained of third molar problems when making an appointment. The third molars were mostly mandibular, partly erupted, and distoangularly oriented. Severity of discomfort and interference with daily activities were graded by the patients on average as 5.0 (SD +/- 2.7) and 3.6 (SD +/- 2.9), on a scale from 0 through 10. Distoangular lower third molars caused the most discomfort and interfered most with activities of patients. The risk of acute disease in patients with distoangularly oriented third molars was 3.6 times that in other patients. Bivariate analysis showed that if the follicle of a distoangular third molar were enlarged, the risk of acquiring acute disease was 44 times that in other patients. It was concluded that early removal of partially erupted and distoangularly oriented lower third molars is recommended, especially when they are associated with an enlarged follicle. PMID- 8361721 TI - Temporomandibular joint dysfunction and facial pain caused by neoplasms. Report of three cases. AB - The most frequent causes of painful limitation of temporomandibular joint function are myofascial pain dysfunction or anterior disk displacement. A potential problem in dealing with those patients is the risk of misdiagnosing the rare patient who has a neoplastic disease, primary or metastatic to the epipharyngeal region, parotid gland, jaws, or temporomandibular joint. Three cases are presented in which progressively worsening limitation of mandibular movement and increasing pain led to the diagnosis of a neoplasm in the temporomandibular joint region. The article illustrates the necessity of performing a thorough clinical and radiographic examination. PMID- 8361722 TI - Intracranial schwannoma as atypical facial pain. Case report. AB - Facial pain is a common complaint that leads those who have it to seek professional help. Often times, the general dentist is the first clinician that a patient consults because of a presumed odontogenic origin of the pain. Occasionally a small number of these patients will be found to have an intracranial tumor. The case reported here is one such patient who was diagnosed and treated for a seventh nerve schwannoma. PMID- 8361723 TI - Bilateral parotid swelling associated with chronic obstructive pulmonary disease. A case of pneumoparotid. AB - Acute enlargement of the parotid glands due to air insufflation is well reported under various names, the most appropriate of which is pneumoparotid. We report an unusual example of pneumoparotid, which was difficult to diagnose, that involved background swelling of the parotids because of the respiratory effort of chronic obstructive pulmonary disease and acute exacerbations associated with episodes of coughing. PMID- 8361724 TI - Accidental displacement of a lower third molar. Report of a case in the lateral cervical position. AB - A report of a case of the accidental displacement of an unerupted third molar to the lateral region of the neck as a complication of exodontia. A review and an analysis of the possible causes of this rare complication is included. PMID- 8361725 TI - Changes in the oral microflora during cytotoxic chemotherapy in children being treated for acute leukemia. AB - Thirty-four children with diagnosed cases of acute leukemias and being treated with cytotoxic chemotherapy at St James' Hospital, Leeds, were followed for between 6 months and 1 year to determine the changes in their oral microflora. They were examined before treatment commenced and then at monthly intervals. Swabs were taken from the oral cavity to test for the presence or absence of bacteria and Candida. Saliva samples were also used to assess the levels of Streptococcus mutans in the mouth. Sensitivity tests were carried out to assess the effect of the cytotoxic agents on the oral flora. All children received prophylactic nystatin and chlorhexidine gluconate mouthrinses four times daily for the whole period of the study. There was significant difference (p < 0.0001) for counts of S. mutans at different treatment stages. Sensitivity tests showed that S. mutans was sensitive to the cytotoxic drug daunorubicin, and this drug was probably responsible for the fall in S. mutans counts. A significant difference was also found in the types of bacteria isolated between the study and reference groups, but there was no change in the composition of the flora in the study group during treatment. These bacteria were also found to mirror those cultured from routine blood samples in children with acute leukemia. PMID- 8361726 TI - Risk factors for oropharyngeal candidiasis in patients who receive radiation therapy for malignant conditions of the head and neck. AB - Twenty-seven consecutive patients receiving radiation to the head and neck were followed to assess risk factors for the development of candidiasis. One-third of the patients developed oral candidiasis during radiation therapy. Xerostomia was shown to correlate with risk of oropharyngeal infection (p = 0.033). The presence and use of oral prostheses were shown to correlate with oral colonization of Candida albicans before radiation therapy (p = 0.011). Alcohol use and smoking represent risk factors for oral colonization by Candida during radiation therapy (p = 0.023 and p = 0.045 respectively). These factors must be assessed in future studies of oropharyngeal candidiasis in radiation therapy. PMID- 8361727 TI - Oral findings in patients with active or inactive Crohn's disease. AB - The frequency and type of oral mucosal lesions, dental infections, and salivary constituents were evaluated in 53 patients with Crohn's disease, who were divided into inactive, mildly active, and severely active groups on the basis of clinical and endoscopic criteria. Buccal biopsies from nine patients with active disease showed morphologic changes that suggested Crohn's disease-related lesions. Panoramic radiographs revealed more infectious foci in the teeth of patients with active Crohn's disease than in patients with inactive disease. Salivary flow rate, buffering capacity, total protein, amylase, and IgA and IgG concentrations did not differ with respect to the activity of Crohn's disease. The observed mucosal inflammation in patients with active Crohn's disease, although high in frequency, was mild and did not need therapy, but the great number of dental infections in association with the activity of Crohn's disease should be taken into account in the treatment of these patients. PMID- 8361728 TI - Globulomaxillary cyst revisited. AB - Classically, the globulomaxillary cyst was considered to be an inclusion or developmental cyst that arises from entrapped nonodontogenic epithelium in the globulomaxillary suture. Subsequently Christ disputed the existence and histogenesis of this lesion stating that the evidence indicated that facial processes per se did not exist. The development of the anterior maxilla was attributed to the merging of growth centers rather than fusion of facial processes, and hence ectodermal entrapment was ruled out. Recent embryologic studies, however, have demonstrated that Christ's view of facial development was incorrect. Fusion of facial processes does occur, and epithelium is entrapped in areas that later will lie between the maxillary lateral incisors and canines. This review argues that embryologically and histopathologically the globulomaxillary cyst should again be considered as an identifiable clinicopathologic entity. PMID- 8361729 TI - The so-called "globulomaxillary cyst" is extinct. PMID- 8361730 TI - Clinical features of a family with X-linked amelogenesis imperfecta mapping to a new locus (AIH3) on the long arm of the X chromosome. AB - X-linked amelogenesis imperfecta is a condition that affects dental enamel characterized by vertical banding of the enamel in heterozygous females in contrast with more uniform appearances in males. The clinical features of a family with amelogenesis imperfecta are described. The disease in this family has been shown to be unlinked to the amelogenin gene locus on the distal short arm of the X chromosome. It maps instead to a locus on the long arm of the X chromosome in the Xq22-q28 region. There was considerable variability in clinical features in affected females in this family in contrast with the more consistent findings in families linked to the amelogenin gene locus region. PMID- 8361731 TI - Enamel ultrastructure and protein content in X-linked amelogenesis imperfecta. AB - X-linked amelogenesis imperfecta has been proven in a number of families to be linked to or involve a variety of mutations in the X chromosome amelogenin gene. The purpose of this study was to characterize the enamel ultrastructure and enamel protein in a kindred affected by X-linked amelogenesis imperfecta. Exfoliated primary teeth were obtained from two related persons (one male, one female) who had X-linked amelogenesis imperfecta with marked hypoplasia. Normal enamel (age and sex matched) was used as the control for all analyses. The teeth were evaluated using light microscopy, scanning electron microscopy, and microradiography. The enamel of the heterozygous female was hypoplastic and rough with marked surface depressions. Enamel beneath these depressions was poorly organized and lacked a prismatic structure. The affected male had very thin enamel (approximately 40 microns) that also lacked an organized structure. Enamel protein from the teeth of the heterozygous female and the control was characterized using amino acid analysis. The protein content of the enamel of the female with amelogenesis imperfecta was 0.40% (N = 1) whereas the control enamel ranged from 0.17% to 0.45% (N = 4; mean = 0.34%). This study indicates that although the enamel in both the male and female with X-linked amelogenesis imperfecta displayed marked structural abnormalities the enamel protein was similar in quantity and amino acid composition for normal and X-linked amelogenesis imperfecta (female) enamel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361732 TI - Chronic idiopathic hyperphosphatasemia. Case report. AB - Chronic idiopathic hyperphosphatasemia, or juvenile Paget disease is a very rare syndrome that is characterized by fragile bones, bowing deformities, shortness of stature, large head, premature loss of teeth, radiographic evidence of expanded osteoporotic long bones with coarse trabeculations, and widened bones of the skull. Increased levels of serum alkaline phosphatase and increased levels of urinary total hydroxyproline are notable. We present a case of juvenile Paget disease that was associated with a history of precocious puberty. The patient had odontogenic osteomyelitis of the mandible that was treated by drainage, surgical debridement and antibiotic therapy. PMID- 8361733 TI - Investigation into the histogenesis of congenital epulis of the newborn. AB - Five previously unreported cases of congenital epulis of the newborn are presented. All five cases were on the anterior maxillary alveolar ridge. Four were removed at 2 days of age and one at 7 weeks. Light microscopy demonstrated large eosinophilic granular cells within vascular fibrous connective tissue. Immunohistochemical studies revealed a positivity for vimentin and neuron specific enolase. Cytogenetic evaluation performed on one case was normal. Estrogen and progesterone receptors were absent in the one case so studied. Electron microscopy demonstrated tumor cells that were filled with autophagosomes. Cellular organelles were significantly reduced and inversely related to the number of cytoplasmic autophagosomes. Many of the autophagosomes contained collagen precursors. Poorly formed junctional complexes were seen. Occasional tumor cells demonstrated long processes that contained contractile microfilaments, pinocytosis, and areas of exocytosis. These studies suggest the tumor cells represent early mesodermal cells that express pericytic and myofibroblastic features that undergo cytoplasmic autophagocytosis. PMID- 8361734 TI - Role of T cells in the pathogenesis of periapical lesions. A preliminary report. AB - The pulps of mandibular molars of 15 athymic and 15 conventional rats were surgically exposed and left open to their oral flora. Each group was divided into three subgroups of five animals each. The rats were killed after their pulps were exposed for 2, 4, or 8 weeks. After fixing, decalcifying, and embedding, the specimens were sectioned and stained with hemotoxylin and eosin. They were then examined under a microscopic grid and quantified by percentages of surface areas of bone, connective tissue, bone marrow, intrabony spaces, periapical lesions, and numbers of osteoclasts, with the use of a DataVoice computerized data collection and analysis system. Statistical analysis showed no significant difference between periapical tissue responses of the conventional and athymic groups. The results indicate that the pathogenesis of periapical lesions is a multifactorial phenomenon and is not totally dependent on the presence of T-cell lymphocytes. PMID- 8361735 TI - Electron microscopic changes in human pulps after intraligamental injection. AB - Because of its advantages, intraligamental injection is becoming a popular anesthetic technique to achieve anesthesia in vital pulps. This study investigated the possible effects of intraligamental injection on human pulps under electron microscope. Forty-two mandibular and maxillary premolars were scheduled to be extracted for orthodontic reasons after being anesthetized with intraligamental injections of 2% lidocaine, 1:100,000 epinephrine (experimental group). The same anesthetic solution was used on the contralateral teeth with either nerve or field blocks (control group). To examine the effects of ischemia on odontoblasts, 12 anesthetized premolars were extracted, and their pulps were placed in physiologic saline solution for different time intervals (15 minutes to 6 hours). The teeth in the experimental and control groups were then reanesthetized with nerve or field blocks of 3% carbocaine without epinephrine after time periods that ranged from 15 minutes to 28 days. After extraction, the teeth were sectioned vertically and their pulps were fixed in 3% glutaraldehyde. The odontoblastic layer of each pulp was examined under electronic microscope. Nuclear and cytoplasmic changes started an hour after ischemia in the pulps placed in physiologic saline. In contrast, little or no cellular changes occurred in pulps of the experimental or controls groups. On the basis of the results, it appears that intraligamental injection has no long-term deleterious effects on pulps of young human premolars. PMID- 8361736 TI - Effect of recapitulation on accuracy of electronically determined canal length. AB - The accuracy of an electronic apex locator to measure canal length during instrumentation when nonrecapitulated dentin debris is present has not been evaluated. The purposes of this study were (1) to compare actual with electronic canal length before and after instrumentation, and (2) to compare the accuracy of electronic length in recapitulated and nonrecapitulated canals. Actual canal lengths of 30 mature anterior teeth were determined, teeth mounted in an in vitro system, and canal lengths determined with the electronic apex locator. Canals were step-back prepared to a size 35 file. Fifteen canals were recapitulated and the other 15 were not. Canals were dried and lengths again determined with the electronic apex locator. Data showed that for electronically determined versus actual lengths: 1) 63% were longer, 23% equal, and 13% shorter before instrumentation, 2) 30% were longer, 0% equal, and 70% shorter after instrumentation, 3) instrumentation caused a mean shortening of 0.63 mm, and 4) recapitulation of nonpatent canals was necessary to obtain length reading with the electronic apex locator. PMID- 8361737 TI - Observer variation in interpretation of magnetic resonance images of the temporomandibular joint. AB - The purpose of this study was to measure interobserver and intraobserver variation in reporting magnetic resonance images of the temporomandibular joint. This study was based on magnetic resonance images of 149 joints. The images were interpreted independently by two of us on two occasions, 2 to 4 weeks apart. We were trained together before starting the study. The magnetic resonance images were interpreted for the position and configuration of the disk and osseous changes. The intraobserver agreement for reporting the position of the disk was 95%, configuration of the disk was 90%, and osseous changes was 97% (average of both observers). The agreement between the two observers was 90% on the position of the disk, 89% on the configuration of the disk, and 94% on reporting osseous changes (average of both readings). The results suggest that interobserver and intraobserver variation in reporting magnetic resonance images of the temporomandibular joint can be kept at a low level with high quality images, suitable training of the observers, and well-defined criteria for interpretation. The low observer variation together with the high diagnostic accuracy reported in other studies suggests that magnetic resonance imaging of the temporomandibular joint is a reliable and valid imaging technique for assessment of this joint. PMID- 8361738 TI - Direct digital dental x-ray imaging with visualix/VIXA. AB - Visualix (VIXA in North America) is a new commercial system for direct dental x ray imaging. It is based on a special charged-coupled device sensor and a personal computer platform with dedicated peripherals. Application software is installed that manages the operation of the sensor and provides a user interface specifically conceived for real time imaging. Given the high sensitivity of the sensor and the corresponding low dosage required, the performance of the system in terms of signal-to-noise ratio is essentially determined and limited by the quantized nature of the original radiologic information in the x-ray beam. At full scale range, the dose requirements are approximately six times less than those for a D-speed film. PMID- 8361739 TI - Layer thickness in panoramic radiography as defined by different noise-equivalent passbands. AB - The layer thickness in rotational panoramic radiography is presented with the use of the concept of the noise-equivalent passband. Conventionally, the layer thickness has been calculated only from one-dimensional data in the horizontal or rotational dimension of panoramic radiography. In the present study, results from calculations using both one- and two-dimensional data are presented. When the vertical dimension is included in the calculations, the layer is wider than when calculated from data in the horizontal dimension only. It is pointed out that the wider layer that follows from the introduction of the vertical dimension may be the most reliable measure of layer thickness in panoramic radiography. PMID- 8361740 TI - Computed tomography of the jaws in familial adenomatosis coli. AB - Familial adenomatosis coli is known to be associated with tooth impactions, odontomas, and osteomas. Three cases were examined by panoramic radiography and computed tomography. Computed tomography was especially useful for detecting osteomas in the maxilla and also revealed a wavy cortical thickening in the mandible in one instance. The latter finding has been reported for other bones in the body but not previously for the mandible. PMID- 8361741 TI - Pencil injury. PMID- 8361742 TI - Iodoform gauze with a radiopaque filament. PMID- 8361743 TI - Paramolar with bifid crown. PMID- 8361744 TI - Supernumerary teeth in twins. PMID- 8361745 TI - [Surgical management of left cor triatriatum in adults]. AB - Cor triatriatum sinistrum is a rare congenital cardiac anomaly in which a membrane divides the left atrium. Severity of the disease depends on the size of the opening on the membrane. The anomaly presents with severe pulmonary hypertension and prognosis is unfavourable without surgery. From 1976 through 1992, 5 adult patients were treated surgically in our institution. Cor triatriatum can be corrected surgically with a low mortality and excellent late results if an early preoperative diagnosis has been made. Clinical findings and cardiac catheterization do not provide sufficient data for the correct diagnosis. From a review of our experience it is concluded that echocardiography is superior to angiography for diagnosing cor triatriatum. PMID- 8361746 TI - [Lymph drainage from the breast to the parasternal lymph nodes]. AB - Breast lymphography revealed linkage between the axillary and parasternal lymph nodes in three out of 55 patients with breast cancer. In all the cases the efferent lymph vessels outlined laterally and, according to Berg's scheme, lymph node groups I, II and III were filled. Lymph vessel responsible for the filling of the parasternal lymph nodes branched from the area of group I lymph nodes. In two out of the 3 cases axillary metastasis was detected in one case, however, the axillary was found unaffected. The lymph vessel linkage observed doesn't seem to support the widely accepted concept, according to which there are only direct efferent lymph vessels running from the breast to the parasternal lymph nodes. This finding also explains why the incidence of parasternal metastases in the breast is higher in the case of tumorous obstruction of the axillary lymph nodes. PMID- 8361747 TI - [Azidothymidine in the management of immune deficiency complex]. AB - The nucleoside-analogue azidothymidine is the first effective drug in the management of HIV-infection although it is not a causal therapy. Azidothymidine increases the life-span of the HIV-positive patients, decreases the incidence of opportunistic infections and enhances the quality of life. The current recommendations is to use the drug at a dose of 500 mg daily in persons with CD4+ counts of less than 500. The (unwanted) side-effects are less prominent at this lower dose. Although there is a very significant research work all over the world for newer drugs for HIV-therapy, it seems that for the foreseeable future azidothymidine will remain the cornerstone of antiretroviral therapy. PMID- 8361748 TI - [Ophthalmoplegia in herpes zoster: clinical review based on two case reports]. AB - The authors describe two cases of ophthalmic herpes zoster complicated with ophthalmoplegia. This rare complication developed in the 2nd week after beginning of the disease and it is only slightly influenced by antiviral therapy, but improvement was observed after the administration of corticosteroids. A short overview summarizes the diagnostic possibilities, the therapy and the complication of the disease. PMID- 8361749 TI - [Parenteral administration of fat-soluble vitamins]. PMID- 8361750 TI - [Trends in therapy by "manipulation", basic concepts of manual therapy]. PMID- 8361751 TI - Suppression in transformed avian fibroblasts of a gene (crp) encoding a cysteine rich protein containing LIM domains. AB - Using cDNA subtraction and differential hybridization techniques, a cDNA library derived from normal quail embryo fibroblasts was screened for clones corresponding to genes whose expression was suppressed in v-myc-transformed, as compared with normal, quail embryo fibroblasts. One of the isolated cDNA clones corresponded to a 0.9-kb mRNA that was present in normal quail and chicken embryo fibroblasts, but was virtually absent from all transformed avian cells tested: quail embryo fibroblasts transformed by the v-myc, v-myc/v-mil or v-src oncogenes, cells derived from a methylcholanthrene-induced quail fibrosarcoma or v-myc-transformed chicken macrophages. Nucleotide sequence analysis of the original and supplementary cDNA clones indicated that the corresponding gene encodes a 194 amino acid cysteine-rich protein (M(r) 20,911). A database search revealed that the gene is the avian homolog of a human primary response gene (crp) of unknown function. Both the quail and human CRP proteins contain two copies of a cysteine-rich amino acid sequence motif (LIM) with putative zinc binding activity that was previously identified in several proteins with presumed regulatory functions essential for cell growth or differentiation. PMID- 8361753 TI - Molecular cloning and characterization of the mouse RB1 promoter. AB - We report the isolation and characterization of the mouse RB1 promoter and surrounding DNA sequences, and the identification of elements required for basal transcriptional activity. The mouse RB1 promoter, like the human homologue, has a high G + C content, constitutes a CpG island and is devoid of typical TATA and CAAT boxes. The first 235 base-pairs upstream of the translation initiation codon in the mouse promoter exhibit 80% sequence homology with the human sequence. This homology includes a region which contains putative binding sites for the transcription factors Sp1, ATF and E2F/DRTF1. Four major transcription initiation sites were identified downstream of this conserved region. Mutational analysis revealed that the Sp1 and ATF binding sites, but not the putative E2F/DRTF1 binding site, are critical for promoter activity. Complete disruption of the putative Sp1 and ATF sites abrogated transcription, whereas the introduction of point mutations, previously identified in the Sp1 and ATF sites in two low penetrance retinoblastoma families, reduced promoter activity in a cell type specific manner. Less reduction in activity occurred in retinoic acid induced differentiated P19 cells and NIH3T3 mouse fibroblasts than in undifferentiated embryonal carcinoma P19 cells. Activity of the RB1 promoter was found to be stimulated in retinoic-acid induced differentiated P19 cells compared to undifferentiated P19; this stimulation required intact Sp1 and ATF sites but not the putative E2F/DRTF1 binding site. Our results indicate that basal level of RB1 expression is governed by Sp1 and ATF. PMID- 8361752 TI - The carboxy-terminal domain of c-Myb activates reporter gene expression in yeast. AB - We have shown previously that c-myb expressed in the yeast S. cerevisiae mediated efficient transcriptional activation of reporter genes designed with specific Myb Recognition Elements (MRE's), confirming that this proto-oncogene is able to function as a regulator of transcription in that heterologous context. Here we show that in yeast, as in higher eucaryotic cells, the central domain of c-Myb displays transactivating capacity. In yeast, however, the carboxy-terminal region, defined as a negative regulatory domain in higher cells, activates transcription as well and appears to be a more potent transactivating domain than the central domain itself. Within this region two domains, namely C1 and C2, have been defined that contribute about equally to the activity of the carboxy terminal region. C1 spans the sequences missing in AMV v-myb while C2, which contains the leucine-zipper motif is specifically absent in the E26 v-myb in addition to C1. The c-Myb DNA-binding domain itself has no effect on the level of transcription in yeast. We also show that AMV v-Myb stimulates gene expression in yeast with about half the efficiency of full length c-Myb. The fact that the carboxy-terminal region either stimulates or inhibits transactivation properties of c-Myb, depending on the cellular context, stresses the participation of putative c-Myb partner proteins in Myb regulated processes and reopens the question of whether the oncogenic activation of c-myb is indeed due to the increased transactivation capacity of its onco derivatives. PMID- 8361754 TI - Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. AB - The v-maf oncogene of the avian musculoaponeurotic fibrosarcoma virus, AS42, encodes a nuclear protein which contains a characteristic b-Zip domain. By screening a chicken embryo fibroblast (CEF) cDNA library under moderately stringent hybridization conditions, we picked up a series of cDNA clones for a novel maf-related gene which we named mafK. We also identified another maf related gene named mafF by screening a chicken genomic library using a mafK probe. Structural analyses suggested that the mafK and mafF genes consist of three exons. The exon-intron structures of the two genes resemble each other, but differ from that of the chicken c-maf gene. As compared to the c-Maf protein, the proteins encoded by the mafK and the mafF genes are rather small in size and lack the regions corresponding to the amino terminal acidic domain present in the c Maf protein. On the other hand, the structures of the b-Zip domain are well conserved among these Maf-related proteins. When overexpressed by using an avian retroviral vector, the two maf-related genes did not induce morphological transformation of CEF cells but induced colony formation in soft agar with very low efficiencies. With a specific antibody, the MafK protein was detected predominantly in the nuclei of the cells infected with the virus which carries the mafK gene. Tissue distributions of these three maf-family genes are different from one another, probably reflecting their different functions in vivo. PMID- 8361755 TI - A trans-activator Tax of human T-cell leukemia virus type 1 binds to NF-kappa B p50 and serum response factor (SRF) and associates with enhancer DNAs of the NF kappa B site and CArG box. AB - A transcriptional activator of human T-cell leukemia virus type 1 (HTLV-1) activates at least three distinct enhancers: the viral 21-bp enhancer, the NF kappa B binding site of the IL-2R alpha gene and the CArG box of the c-fos gene. To understand the mechanisms of Tax transactivations of the NF-kappa B enhancer and CArG box, the interactions of Tax protein with their binding factors were analysed. Using a DNA affinity precipitation (DNAP) assay, we found here that Tax associates with the DNA sequences of the NF-kappa B site and CArG box. These Tax associations with enhancers were observed only in the presence of a nuclear factor(s) and were equal to the activating capacities of Tax mutants. To identify the nuclear factor(s), we defined conditions under which no Tax binding to the NF kappa B binding site and CArG box was detected with a nuclear extract of 293T cells. Under these conditions, transfections with cDNAs of the NF-kappa B p50 and serum response factor (SRF) produced a factor(s) that mediated Tax binding to the NF-kappa B site and the CArG box respectively. Furthermore, purified Tax protein interacted with purified NF-kappa B p50 and purified SRF, indicating their direct bindings. These observations indicate that Tax protein associates with enhancer sequences of the NF-kappa B site and CArG box through NF-kappa B p50 and SRF respectively. Previously we demonstrated that Tax interacts with CREB and CREM proteins that bind to the 21-bp enhancer DNA. These results together suggest that indirect binding of Tax to DNA through each enhancer binding protein is a general mechanism for Tax transactivation of transcription. PMID- 8361756 TI - Transforming activity and tissue tropism of hybrid retroviral genomes containing portions of the v-abl and v-src oncogenes. AB - The v-abl and v-src oncogenes encode activated cytoplasmic tyrosine kinases with considerable sequence similarity. The v-abl oncogene of the Abelson murine leukemia virus exhibits a narrow tissue tropism for transformation, almost exclusively forming pre-B-cell tumors, while the v-src oncogene can induce a variety of sarcomas and other tumors. To localize the determinants of the narrow tropism of the v-abl gene, we generated a series of hybrid retroviral genomes containing portions of the v-abl and v-src oncogenes in a Moloney murine leukemia virus backbone. Each virus was tested for transforming activity in NIH3T3 cells; for transforming activity on bone marrow cultures; and for pathogenicity in newborn mice. Many of the hybrid oncogenes carried by these viruses exhibited transforming activity, and demonstrate that the SH2 domain of each oncogene can be utilized by the kinase domain of the other oncogene for that activity. The results further suggest that a portion of the C-terminal region of v-abl is necessary for the pre-B-cell specificity of the oncogene. PMID- 8361757 TI - H-ras and raf-1 cooperate in transformation of NIH3T3 fibroblasts. AB - We examined the effect of overexpression of growth factor-regulated second messenger enzymes, alone and in combination, on transformation of NIH3T3 cells. Signal transducers included phospholipase C-gamma (PLC-gamma), protein kinase C gamma (PKC-gamma), and two proto-oncogenes, c-H-ras and c-raf-1. Three of these proteins, PLC-gamma, PKC-gamma and Raf-1, did not transform NIH3T3 cells alone or in combination. c-H-ras, which under its own promoter control has low transforming activity, also did not cooperate with PLC-gamma or PKC-gamma. In contrast, the combination of normal or oncogenic p21 H-Ras with the Raf-1 kinase dramatically increased transformation efficiency. The level of Ras protein required for transformation was reduced in Raf-1 co-transfectants, implying that, at low levels of p21 Ras, p74 Raf-1 is rate limiting. As transformation by Ras depends on jun-mediated transcriptional events, we also examined H-ras and c-raf 1 cooperation in transcriptional transactivation of TPA-responsive element (TRE) dependent reporters. Like the H-ras/c-raf-1 cooperation in transformation, we observed this synergistic stimulation of TRE-dependent transcription. This pathway for transformation and transcriptional activation by increased levels of normal Ras and Raf may be important in tumors that show overexpression but lack mutationally activated forms of these two proto-oncogenes. PMID- 8361758 TI - Several mutant p53 proteins detected in cancer-prone families with Li-Fraumeni syndrome exhibit transdominant effects on the biochemical properties of the wild type p53. AB - The identification of germ-line mutations in the p53 gene has provided a situation where comparable amounts of wild-type and mutant p53 co-exist in constitutional cells of certain individuals who are cancer-prone. Here we report the biochemical characteristics of several Li-Fraumeni syndrome associated mutant p53 proteins in order to assess the influence of germ-line mutant p53 on the functions of the wild-type p53. Unlike 248W mutant p53 protein, which was previously shown to have no effect on the wild-type p53 conformation (Milner & Medcalf, 1991; Cell 65, 765-774), germ-line associated mutant p53 proteins with residue 133T, 245D or 258K, converted the wild-type p53 conformation into the mutant conformation. Furthermore, lysates containing cotranslated wild-type p53 and these mutant p53 proteins were significantly impaired for DNA and SV40 large T antigen binding. These observations suggest that at least some germ-line p53 mutants might exhibit dominant effects on wild-type p53 functions and, like other mutant p53 proteins, the phenotype of germ-line mt p53 proteins might be variable depending on the particular mutation. PMID- 8361759 TI - Isolation and chromosomal localization of CRKL, a human crk-like gene. AB - We have identified and partially characterized a gene located on chromosome 22, band q11, centromeric of the chronic myelogenous leukemia breakpoint region. A number of overlapping cDNAs were isolated from this locus and the largest of 1.8 kb was sequenced. Its deduced amino acid sequence shows homology to the SH2 domains of protein tyrosine kinases such as FER, and is strikingly similar to the cellular part of the v-crk oncogene product. We identified one SH2 and two SH3 domains within the 303 amino acid open reading frame of this crk-like gene, CRKL. The CRKL gene product is predicted to have a molecular mass of 36 kDa. In addition, we demonstrate that this gene does not represent the human homolog of v crk but rather a novel gene potentially capable of mediating the transduction of intracellular signals. PMID- 8361760 TI - MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations. AB - T-cell lymphoproliferative diseases are often associated with recurrent chromosomal translocations involving T cell receptor genes (TCR) and genes that are thought to play a role in the pathogenesis of these diseases. Whereas numerous such genes have already been identified in acute T cell leukemias, no candidate gene has yet been identified to play a role in the heterogeneous group of T cell proliferations with a mature phenotype. We here report the molecular cloning of two examples of the rare but recurrent t(X;14) translocation. The first translocation was associated with a benign clonal proliferation in an ataxia telangiectasia patient and the second with a T cell prolymphocytic leukemia. Both translocations implicated the TCR alpha/delta locus and a common breakpoint region on chromosome Xq28. A previously unidentified gene, abnormally transcribed in both T cell proliferations, was characterized in the immediate proximity of the breakpoints. This Xq28 gene has no homology with known sequences, uses a complex alternative splicing pattern and demonstrates two short open reading frames. This gene, named MTCP-1 (Mature T Cell Proliferation-1) is the first candidate gene potentially involved in the leukemogenic process of mature T cell proliferations. PMID- 8361761 TI - The v-Rel oncoprotein increases expression from Sp1 site-containing promoters in chicken embryo fibroblasts. AB - The v-Rel oncoprotein of the avian Rev-T retrovirus is a member of a family of related transcription factors, which also includes the subunits of NF-kappa B and several other interacting cellular proteins. We show here that v-Rel specifically increased expression from a reporter plasmid containing multiple Sp1 binding sites approximately sixfold in chicken embryo fibroblasts (CEFs), even though v Rel did not bind directly to these sites. v-Rel also increased expression from a reporter plasmid containing a human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in which the kappa B binding sites were mutated but which still contained intact Sp1 binding sites. The increase in Sp1-site transactivation does not precisely correlate with transformation by v-Rel since one non-transforming v-Rel mutant still induced expression from the Sp1 site containing promoter. v-Rel appears to increase expression from Sp1 site containing promoters by affecting the transactivation domain of Sp1, since v-Rel increased the activity of a Gal4-Sp1 fusion protein, which contains the Sp1 transactivation domain but lacks the Sp1 DNA-binding domain. As compared with v Rel, c-Rel induced only a slight increase in expression from the reporter plasmid containing Sp1 sites. However, v-Ras and v-Src (but not v-Myb) induced increases in transcription from the reporter plasmid containing Sp1 sites to the same extent as v-Rel, but through pathways that appear to be independent from v-Rel. These results suggest that certain oncoproteins might increase transcription from many genes that contain Sp1 binding sites, and that this might be important for certain aspects of transformation by these proteins. PMID- 8361762 TI - p54c-ets-1 and p68c-ets-1, the two transcription factors encoded by the c-ets-1 locus, are differentially expressed during the development of the chick embryo. AB - The chicken c-ets-1 proto-oncogene encodes two transcription factors, p54c-ets-1 and p68c-ets-1, which contain the same DNA-binding domain but differ in their transactivating activities. We have investigated the spatial and temporal distribution of the transcripts encoding p54c-ets-1 and p68c-ets-1 throughout the development of the chick embryo. We report that p68c-ets-1 as well as p54c-ets-1 is expressed in a wide variety of cells of mesodermal origin, including endothelial cells and mesenchymal cells interacting with epithelium. However, whereas p54c-ets-1 transcripts are detected in most cells, p68c-ets-1 transcripts are restricted to a subset of these cells, randomly distributed. In contrast, p54c-ets-1 is expressed in the absence of p68c-ets-1 in T and B lymphocytes. We show that, during erythropoiesis, both p68c-ets-1 and p54c-ets-1 are expressed in immature erythroid cells in extraembryonic blood islands. The pattern of expression of p54c-ets-1 and p68c-ets-1 during embryonic development suggests the involvement of these transcription factors in the regulation of morphogenetic processes. In addition, we provide the first clue that p68c-ets-1, the cellular progenitor of the v-ets oncogene, is expressed in erythroid cells. This result is very important with respect to the properties of the v-ets oncogene, which confers on the retrovirus E26 the ability to transform erythroid cells. PMID- 8361763 TI - Role of first exon/intron sequences in the regulation of myc family oncogenic potency. AB - cis-Acting sequence elements that participate in the regulation of myc family gene expression in normal tissues and that serve as potential targets for the deregulation of expression in tumors have been localized to the first exon/intron region of all three myc family genes. To test directly the importance of these cis elements in the tumor-associated deregulation of myc family gene expression, we have compared the oncogenic activities of complete (exons 1, 2 and 3) and truncated (exons 2 and 3 only) c-, N- and L-myc expression constructs in the rat embryo fibroblast (REF) cooperation assay. Removal of the first exon/intron region from each construct was associated with a dramatic increase in oncogenic potency by several criteria. Analysis of N-myc/ras-transformed cell lines demonstrated (i) fewer transfected N-myc gene copies and an overall higher level of steady-state N-myc mRNA with the truncated N-myc expression construct and (ii) the presence of a significant block to transcriptional elongation in the first exon of the complete N-myc expression construct. These results indicate that the first exon of N-myc plays an important role in governing oncogenic potency, possibly through transcriptional control mechanisms. PMID- 8361765 TI - Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain. AB - The product of the retinoblastoma tumor suppressor gene (pRb) and p107 share a high degree of structural homology in the pocket region, which is thought to play a primary role in the function of these proteins. It is conceivable that there exists a larger family of cellular proteins containing this pocket region. In this communication, we report cloning of a new human cDNA encoding a polypeptide that shows a high level of identity with pRb and p107 and possesses a pocket region. We have named it pRb2. From the deduced amino acid sequence, pRb2 has a predicted molecular weight of approximately 120 kD and its in vitro translated product binds to the adenovirus E1A protein. Due to its size, pRb2 may correspond to p130, which has previously been shown by us to interact with the transforming region of E1A in in vivo studies. Interestingly, pRb2 fails to bind an E1A mutant in the transforming domain 2 suggesting that pRb2 is involved in the transforming capacity of E1A. PMID- 8361764 TI - Novel DNA binding of p53 mutants and their role in transcriptional activation. AB - The protein product of the normal p53 gene binds to the DNA p53CON element (GGACATGCCCGGGCATGTCC, Funk et al., 1992), thereby activating transcription from adjacent promoters. Two mutants, 248 (Arg-->Trp) and 281 (Asp-->Gly), failed to bind p53CON and to activate transcription. However, in contrast to previous reports that all p53 mutants fail to bind to the other p53 binding elements, two p53 mutants, 143 (Val-->Ala) and 273 (Arg-->His), retained both p53CON binding and transcriptional activation functions. A third mutant 175 (Arg-->His) bound to the p53CON but did not activate transcription. These data suggest that the DNA binding and transcriptional activation functions of p53 mutants in tumor cells are dependent on the specific missense mutations acquired in the p53 gene and the target sequences of p53 in the genome. PMID- 8361766 TI - I kappa B alpha can localize in the nucleus but shows no direct transactivation potential. AB - Although I kappa B is a cytoplasmic inhibitor of NF-kappa B and c-Rel that prevents nuclear translocation of NF-kappa B, some forms of I kappa B have been found in the nucleus. Given that some other proteins with ankyrin-type repeats are transcription factors, we wondered if a nuclear form of I kappa B alpha could itself be a transcriptional activator. We found that Gal4-I kappa B alpha fusion proteins strongly transactivate a Gal4 site-containing promoter in 3T3 fibroblasts. The I kappa B alpha domain responsible for this transactivation is not the acidic domain of I kappa B alpha, but the ankyrin repeat domain which is responsible for protein-protein interactions. To enhance our ability to detect cellular I kappa B alpha by immunofluorescence, we overexpressed the protein in transfected cells, and found that overexpressed I kappa B alpha is largely cytoplasmic in serum-deprived cells, but nuclear in serum-stimulated cells. However, in cell fractionation studies under all treatment conditions, I kappa B alpha appears mainly in cytoplasmic fractions, suggesting that it can rapidly move out of the nucleus through nuclear pores during extract preparation. Using double antibody immunoprecipitations, we found that I kappa B alpha in proliferating cells is strongly associated with RelA(p65). When I kappa B alpha is fused to the Gal4 DNA-binding domain, nuclear Gal4-I kappa B alpha is associated with RelA(p65). Thus, the activation domain of the associated RelA(p65) molecule could account for the ability of Gal4-I kappa B alpha to transactivate the Gal4 promoter. Unlike Bcl-3, an I kappa B which has been recently shown to directly transactivate through kappa B sites when associated with NFKB2 (p52), I kappa B alpha shows no ability to directly transactivate target promoters via its association with RelA(p65). PMID- 8361767 TI - Structural analysis of the human ret proto-oncogene using exon trapping. AB - A genomic contig of the human ret protooncogene was created with four overlapping cosmid clones isolated from two libraries. After southern analysis with portions of the ret cDNA, eight cosmid fragments were analysed in detail for the presence of ret exons using exon trapping. PCR products corresponding to spliced exons were isolated and subcloned. Exon boundaries were delineated by comparison of the PCR product sequence and the published ret cDNA sequence. The exons were initially positioned on a genomic map defined by BamHI, EcoRI and HindIII restriction sites. The positions of the exons were then refined by amplifying genomic DNA using primer pairs derived from one or more exons along the ret gene, the length of the PCR product indicating the approximate genomic distance between the exon sequences. The ret proto-oncogene is composed of at least 20 exons, ranging in size from 60 bp to 287 bp, distributed along 30 kb of genomic DNA. The extracellular domain is encoded by 10 exons and the cytoplasmic domain by 9 exons. The transmembrane domain is encoded by a single exon. PMID- 8361768 TI - Identification of amino acids in p21ras involved in exchange factor interaction. AB - Through the genetic analysis of vulva development in C. elegans several different sites of mutation have been identified in the let-60 ras protein which have been postulated to affect the function of normal but not oncogenic p21ras (Beitel, G. J., S. G. Clark, and H. R. Horvitz. 1990. Nature 348: 503-509). We have introduced these mutations into mammalian Ha-ras and determined their effect on the function of cellular ras (c-ras), an oncogenically activated variant D12ras and the dominant negative N17ras. From these studies we conclude that two of the mutations S89-->F89 and delta 103-108 destabilise ras when it is in the GDP-bound form. However mutations at A66 and G75 lead to stable proteins on which a ras exchange factor SCD25 is unable to promote the formation of ras-GTP. The mutations at A66 show for the first time that helix alpha 2 of p21ras is involved in the stimulation of guanine nucleotide exchange by exchange factors. PMID- 8361769 TI - Upregulation of mdm-2 expression in Meth A tumor cells tolerating wild-type p53. AB - Overexpression of mouse wild-type p53 (wt p53) in mouse Meth A tumor cells after transfection of wt p53 encoding vectors induced a strong growth-inhibitory response. Cells of only few of randomly selected surviving colonies contained and expressed the transfected wt p53 specific DNA. Despite expressing authentic wt p53, such cells (MethAp53wt) exhibited a similar phenotype as the parental Meth A cells. These cells overexpressed the mdm-2 (mouse double minute-2) gene, both at the RNA and at the protein level. Recently, the MDM-2 protein has been identified as a cellular target of p53, which can abolish its tumor suppressor activity. We, therefore, suggest that MDM-2 has mitigated the growth-inhibitory effect of wt p53 in MethAp53wt cells. Upregulation of mdm-2 expression in MethAp53wt cells was mediated by wt p53, as analysis of Meth A cells carrying a tsp53 (p53Val135) revealed a strict dependence of mdm-2 upregulation upon wt p53 expression. Our results propose that a balanced ratio of MDM-2 and p53 will allow cells to tolerate a limited expression of wt p53. This tolerance is not mediated by a direct inactivation of wt p53 via complex formation with MDM-2, as the majority of both MDM-2 and wt p53 in MethAp53wt cells was not complexed to each other. PMID- 8361771 TI - Joint statement on maintaining professional and legal standards during a shortage of nursing personnel. PMID- 8361770 TI - Unit-based case management benefits patients and nurses. PMID- 8361772 TI - Standards of nursing conduct. PMID- 8361773 TI - Modulation of the allergic reactivity of slum children by helminthic infection. AB - Infection by helminthic parasites can cause the polyclonal stimulation of IgE synthesis, possibly via an enhanced production of interleukin-4 (IL-4), and this has been suggested to influence the allergic reactivity of tropical populations where these parasites are endemic. We evaluated a group of urban slum children in Caracas, Venezuela, with a high prevalence of helminthic infection (70.8%), to establish the relationship between the elevated IgE levels (3696 IU/ml) induced by these parasites and various aspects of the allergic response. Although the absolute levels of IL-4 detected in the sera of these children were low (0.65 +/- 0.20 ng/ml), a strong positive correlation (r = 0.78) was found between these and serum IgE. The cutaneous immediate hypersensitivity reactivity to extracts of common environmental allergens was relatively low (17.5% to house dust), although that to Ascaris extract was moderately high (49.4%). Significant inverse correlations were found between total IgE levels and the different skin test reaction diameters, including Ascaris. The positivity of Prausnitz-Kustner passive transfer tests was low in this group (34%), with a strong inverse correlation (r = -0.75) being found between this and total IgE levels. Significant inverse correlations were also found between total IgE levels and specific IgE antibody to environmental allergens, and to Ascaris antigen. We suggest that the polyclonal production of IgE stimulated by helminthic infection can suppress the allergic response to environmental and parasite allergens via both mast cell saturation and inhibition of specific IgE production. PMID- 8361774 TI - Influence of genes within the MHC on mortality and brain cyst development in mice infected with Toxoplasma gondii: kinetics of immune regulation in BALB H-2 congenic mice. AB - Previous work has shown that genes within the major histocompatibility complex (MHC) of the mouse influence resistance and susceptibility to Toxoplasma gondii infection. Initial studies presented here using B10 H-2 congenic and recombinant haplotype mice inoculated via the oral route with the low virulence Beverley strain of T. gondii confirm the D region localization of MHC-linked control of brain cyst number. All B10 mice were, however, exquisitely sensitive to minor changes in virulence of the parasite inoculum resulting in high mortality during the early acute phase of infection. Further experiments examining mortality and brain cyst number in BALB MHC congenic mice inoculated via different routes indicated that the BALB background would provide a more favourable genetic environment in which to analyse kinetics of MHC controlled immune regulation following infection via the natural (oral) route. In studies comparing d and k haplotype mice a dramatic inverse relationship between splenic CD4:CD8 T cell ratios and brain cyst number was observed, particularly in the strain (BALB/K; H 2k) most susceptible to high brain cyst numbers and subsequent toxoplasmic encephalitis. Of particular interest was the observation that splenomegaly and the relative increase in the splenic CD8 T cell population preceded and accompanied the very dramatic and rapid increase in brain cyst formation. The results suggest that the too rapid development of a potent anti-parasite response in the viscera may drive the parasite to encyst in the brain. PMID- 8361775 TI - Immobilization of Schistosoma mansoni miracidia by activation of the alternate complement pathway at unusually high serum dilution. AB - Free-swimming Schistosoma mansoni miracidia were immobilized by adding normal mammalian serum to the water. Miracidial immobilizing activity (MIA) was shown to result from activating the alternate pathway of complement (APC). MIA in normal sera was heat-sensitive and antibody independent; it was greatly reduced in factor B-depleted or C6-depleted, but not in C1-depleted, human serum. Addition of purified factor B to B-depleted serum totally restored MIA. Half-maximal MIA in normal human, rabbit, and guinea pig sera was detectable at final dilutions exceeding 1/100, 1/200, and 1/500, respectively, and normal rat serum was particularly potent, with MIA at dilutions exceeding 1/2000. Detection of APC activity at such high dilutions is quite extraordinary and attributed to the hypotonic conditions. We confirmed and extended previous findings that heat inactivated infection sera also display MIA. Immobilizing activity in irradiated cercarial vaccine rat serum cofractionated with rat IgG and anti-SWAP antibody activity. Antibody-dependent MIA titres were much lower than for APC-dependent MIA. Based upon light microscope and transmission EM studies, immobilization of miracidia by APC activation was attributed to severe tegumental damage. Miracidia within egg shells were insensitive to MIA. PMID- 8361776 TI - The schistosomulicidal activity and the production of IL-1 and TNF-alpha by peritoneal macrophages from infected mice and their potentiation by muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) treatment. AB - Production of TNF-alpha and IL-1 by adherent peritoneal exudate macrophages (APEM) was monitored for 20 weeks in Schistosoma mansoni infected mice in comparison to their schistosomulicidal activity. LPS-triggered IL-1 and TNF-alpha production by APEM peaked 10 weeks post infection (p.i.) and declined thereafter. The schistosomulicidal activity of APEM also peaked after 10 weeks but remained elevated thereafter. Infected mice were also treated with the immunostimulator liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) 6 or 10 weeks p.i., and their APEM were tested 4 weeks later. APEM from such treated animals showed elevated IL-1 and TNF-alpha production when treatment commenced 6 weeks p.i., while their schistosomulicidal activity increased when treatment commenced either 6 or 10 weeks p.i. The L-arginine inhibitor, NG monomethyl arginine, markedly inhibited the schistosomulicidal activity but not the IL-1 and TNF-alpha production of APEM. Our results show that monokine production increases during the acute phase of infection and declines during its chronic phase, while macrophage schistosomulicidal activity remains constant throughout. Furthermore, TNF-alpha or IL-1 may play a minor role in APEM mediated killing of schistosomula. PMID- 8361777 TI - Ablation of eosinophils with anti-IL-5 antibody enhances the survival of intracranial worms of Angiostrongylus cantonensis in the mouse. AB - Effects of depressed eosinophilia on the development of Angiostrongylus cantonensis in the mouse were studied using monoclonal rat anti-mouse-interleukin 5 antibody (anti-IL-5). The administration of anti-IL-5 strongly depressed peripheral, cerebrospinal fluid (CSF) and medullary eosinophilic responses in mice infected with A. cantonensis, when compared with groups treated with phosphate-buffered saline solution (PBS) alone or isotype-matched rat IgG. There was no significant difference in A. cantonensis antigen specific IgG and IgE antibody responses between rat IgG treated and anti-IL-5 treated mice. Intracranial worm recovery in anti-IL-5 treated mice was consistently high throughout the course of the study and some worms migrated from the brain to the lungs. By contrast, almost all the intracranial worms in the mouse groups treated with PBS alone or rat IgG died before day 32. These data clearly indicate that IL 5 is essential for eosinophil responses in A. cantonensis infected mice and also that eosinophils serve as a potential effector cell in the killing of the intracranial worms in mice. PMID- 8361779 TI - Investing your money the smart way. PMID- 8361778 TI - Immunogenicity in rabbits and monkeys of influenza ISCOMs conjugated with repeated sequences of the Plasmodium falciparum antigen Pf155/RESA. AB - Rabbits and monkeys were immunized with two fusion proteins, ZZ-M3 and ZZ-M5, coupled to pre-formed influenza virus membrane glycoprotein ISCOMs. The fusion proteins comprise two IgG-binding domains from staphylococcal protein A (ZZ) and repeated amino acid sequences from the C-terminal (M3) or central (M5) repeat regions of the Plasmodium falciparum antigen Pf155/RESA. The induced antibody responses were of long duration, could be efficiently boosted and were comparable to those obtained with Freund's Adjuvant. The produced antibodies reacted with M3, M5, protein A and the influenza glycoprotein, recognized Pf155/RESA and inhibited merozoite invasion in vitro. These results suggest that coupling of immunogens to pre-formed ISCOMs may be a basis for construction of multivalent subunit vaccines. PMID- 8361780 TI - The discriminating analysis in the differential diagnosis of monoclonal gammopathies. AB - The clinical diagnosis is not always easy in monoclonal gammopathies. Therefore we used discriminating analysis to obtain diagnosis statistically sure. The parameters considered were kappa-lambda ratio, marrow plasma cells percentage and labeling index, CD3, CD4, CD8 lymphocytic absolute values. The plasma cells percentage and their labeling index make the differential diagnosis between MM and MGUS or SMM and MGUS feasible and quite correct. Additional immunological parameters should be used for the diagnosis between SMM and MM. PMID- 8361781 TI - Atheromatosis and double media: uncommon vascular lesions of renal allografts. AB - Study of 45 renal allograft nephrectomy specimens revealed the presence of relatively uncommon arterial vascular lesions: atheromatosis (12 cases) and a double layer of smooth muscle in the intima (Double Media) (4 cases). Histopathologic features of atheromatosis showed the presence of large lipid laden cells localized in the intimal layer of arteries. Diagnosis of acute vascular rejection (AVR) was made in 19 cases. Diagnosis of chronic vascular rejection (CVR) was found in 4 cases. 22 cases showed lesions of both AVR and CVR. In 12 cases there was infiltration of the intima and media wall by foam cells closely resembling an atheromatous lesion. Four cases of Double Media were found in allografts with survival varying from 51 to 344 days. The presence of either atheromatous or double media does not correlate statistically with immunosuppressive treatment, blood pressure or with the presence of hypertriglyceridemia and/or hypercholesterolemia. Immunohistochemical investigation of atheromatosis revealed total negativity of the foam cells with antisera to: actin, myosin, desmin and myoglobin. Variable reactivity was observed with antisera to vimentin. Myointimal cells of Double Media expressed slight positivity for actin and vimentin. The double media lesion seems to be the result of a reparative vascular process secondary to rejection changes. Atheromatosis seems to be closely correlated to episodes of acute rejection. Vascular lesions in grafts are harbinger of poor prognosis. Double media lesion and atheromatosis do not seem to have a more unfavourable prognostic significance on the evolution of the transplants. PMID- 8361782 TI - [Strongyloides stercoralis hyperinfection with encephalitis manifestations]. AB - A case of encephalitis in a 34 year old woman from Ivory Coast, referred to the Santo Spirito Hospital in Rome, is reported. During a coma which appeared terminal, a bronchoaspirate done for suspicious pulmonary TB, revealed many filariform larvae of Strongyloides stercoralis. A treatment with albendazole has rapidly ameliorated the situation but a relapse after 4 months caused the obitus of the patient. PMID- 8361783 TI - Effect of monensin administration on rat liver glycogen content: preliminary hystological observations. AB - The action of monensin, an electroneutral Na/H antiport, has been studied on liver glycogen content of female rats. The results showed that monensin, when administered in vivo, is able to determine liver glycogen depletion, in agreement with the increase of glycemia and the decrease of insulinemia. Glycogen stores are reformed in 3-4 hours. Moreover, glycogen depletion is more evident in periportal areas, in agreement with "metabolic zonation" of liver carbohydrate metabolism. PMID- 8361784 TI - [Prenatal diagnosis of thanatophoric dysplasia at 21st week of pregnancy]. AB - We report making the prenatal diagnosis of thanatophoric dysplasia without "cloverleaf" skull at 21 weeks gestation. The ultrasound examination showed short and bowed limbs, narrow thorax, and large head. Radiological and histological studies confirmed the aborted fetus to be affected with thanatophoric dysplasia. The differential prenatal diagnosis with other skeletal dysplasias is discussed. PMID- 8361786 TI - [Spondylo-epiphyseal dysplasia tarda with progressive arthropathy: description of a patient whose mother showed minimal features of the disease]. AB - An 8-year-old male patient with Spondylo-Epiphyseal Tarda with Progressive Arthropathy (SEDT-PA) or Progressive Pseudo-rheumatoid Arthropathy of Childhood is reported. Abnormal gait, fatigability, and joint symptoms began at 3 years. Radiological changes were: generalized osteoporosis, platyspondyly, and enlarged epiphyses. The patient's mother showed reduced muscular massa, joint swelling, moderate osteoporosis, and normal vertebrae. SEDT-PA has an autosomal recessive mode of inheritance. In this case, as the propositus' mother showed minimal signs of the disease, either an X-linked trait or an autosomal dominant mutation with variable expressivity could also be assumed. PMID- 8361785 TI - [OEIS complex. Description of a case associated with cardiopathy]. AB - We describe a newborn affected by OEIS complex (Omphalocele--Exstrophy of bladder -Imperforate anus--Spinal defect) associated with atrial septal defect. Terminal ileostomy, closure of the abdominal wall defect and suture of the cecal and vesical plates were performed. The patient died at 5 months and four days. PMID- 8361787 TI - [Fryns syndrome. Description of a case]. AB - We report on a female infant who presents a pattern of malformations including dysmorphic facies, Dandy-Walker anomaly, hypoplasia of the upper lobe of the right lung, associated with diaphragmatic elevation and slight digital anomalies. This whole clinical picture allows us to formulate the diagnosis of Fryns syndrome; this is one of the very few not lethal cases that are reported in literature. PMID- 8361788 TI - Are parents' self-reported total cholesterol levels useful in identifying children with hyperlipidemia? An examination of current guidelines. AB - OBJECTIVE: Recently, the American Academy of Pediatrics (AAP) Committee on Nutrition adopted the recommendation of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (NCEP) that children and adolescents with a family history of premature cardiovascular disease or parental hypercholesterolemia (> or = 240 mg/dL) be screened for hyperlipidemia. The rationale for using parental hypercholesterolemia as a screening trigger is based on sensitivity estimates using parents' actual lipid values. However, in clinical practice pediatricians may often have to rely on parents' self-reported cholesterol levels to determine a child's family risk history. This study examines the feasibility and utility of parental self-reported cholesterol levels as a means of identifying children with elevated total cholesterol levels. METHODS: As part of a school-based risk factor screening program that included total cholesterol measurement, conducted in nine elementary schools between 1989 and 1991, parents of participating children were asked if they had their cholesterol tested in the past year and if they had, to provide their total cholesterol values. RESULTS: If only the children who had one parent with a self reported total cholesterol value > or = 240 mg/dL would have been screened, between 90% and 93% of children with elevated total cholesterol values, either > or = 170 mg/dL or > or = 200 mg/dL, would have been missed. CONCLUSIONS: These data suggest that parents' self-reported cholesterol values are an ineffective means of identifying children with elevated total cholesterol and modification of the current AAP, and NCEP guidelines for selective cholesterol screening in children may be warranted. PMID- 8361789 TI - Comparing prenatal and neonatal diagnosis of hemoglobinopathies. AB - OBJECTIVES: To compare the results of prenatal and neonatal hemoglobinopathy screening, a pilot program was developed at the Northern California Kaiser Permanente Health Care Program, a prepaid health maintenance program serving 2.5 million members. METHODS: In this program, 54,700 pregnant women were screened for hemoglobinopathies. RESULTS: Of the 54,700 women screened, 1019 (1.9%) had a hemoglobinopathy trait, and 81 women with at-risk fetuses were identified. Half the women with fetuses at risk for thalassemia accepted prenatal diagnosis; of those whose fetuses were at risk for sickle-cell disease or other hemoglobinopathies, 30% accepted prenatal diagnosis. Of the 81 at-risk couples, 53 refused amniocentesis for definitive fetal diagnosis; only 28 (35%) accepted; all 4 women who were carrying a fetus with thalassemia major elected to terminate the pregnancy. Only 7 of the 21 cases of hemoglobinopathies were diagnosed prenatally; 14 were discovered neonatally. CONCLUSIONS: Prenatal screening was not found to be an ideal method of identifying hemoglobinopathies of the newborn in this large population. With cost-effectiveness a high priority in health care delivery, we believe that testing of newborns for hemoglobinopathies will continue to be the preferred screening method. A combined prenatal and neonatal program would offer the maximum benefit to patients by adding prenatal counseling, parental options, education, and early complete diagnosis to neonatal screening. PMID- 8361790 TI - Prenatal detection of neuroblastoma: a ten-year experience from the Dana-Farber Cancer Institute and Children's Hospital. AB - OBJECTIVES: To assess the relative frequency of, the clinical and pathological correlates in, and the prognosis of the subset of infants with neuroblastoma who were identified initially by prenatal ultrasonography. DESIGN: Retrospective review of all patients with neuroblastoma evaluated between 1982 and 1992. SETTING: Large, urban, tertiary care children's hospital in Boston, Massachusetts. PATIENTS: Eleven infants with neuroblastoma initially detected with prenatal sonograms were identified. RESULTS: Nine patients had adrenal tumors; two had thoracic paraspinal tumors. Typical diagnostic evidence for neuroblastoma including a palpable abdominal mass and elevations in urinary catecholamines were not commonly seen postnatally. These patients had multiple favorable prognostic indicators including low stage of disease (10/11), favorable biological markers including cellular DNA content (5/5) and N-myc oncogene copy number (5/5), and histopathology suggestive for neuroblastoma in situ (7/11). All patients were treated by surgical resection. One patient exhibited progression of disease postoperatively, but demonstrated a complete clinical response to multiagent chemotherapy. Overall survival in our population was excellent with no deaths seen at a mean follow-up of 37 months (range 3 to 120 months). CONCLUSIONS: Patients with neuroblastoma identified by prenatal ultrasonography generally, although not exclusively, follow a clinically favorable course in which surgical resection is curative. Chemotherapy is not indicated unless substantial progression of disease occurs. PMID- 8361791 TI - Maternal rating of child health at school age: does the vulnerable child syndrome persist? AB - OBJECTIVES: To assess the extent to which parental ratings of child health, including perceived vulnerability to illness, are associated with current and past health events and sociodemographic characteristics of the family and the child. DESIGN: Prospective cohort study of children aged 8 to 10 years previously assessed in infancy in two multi-site studies. SETTING: Thirteen sites largely in eastern United States. PARTICIPANTS: 1877 children representing 65% of those originally selected for follow-up from the two previous studies. Participants were specifically selected on the basis of birth weight so that more than two thirds were low birth weight. MEASUREMENT: Parental interviews at school age including measures of several dimensions of child health and sociodemographic characteristics of the family. The former included a six-item scale assessing parental perceptions of child health overall, and on subscales assessing child current health, previous health, and resistance or susceptibility to illness. Data on health problems at birth were derived from previously collected birth certificates, medical records, and interviews. MAIN RESULTS: Although overall parental perceptions of child health reflected both current and past health events, a clear distinction emerged. Parental rating of current child health and resistance or susceptibility were associated with current child health problems, not events in infancy including very low birth weight. Nonwhite race and maternal rating of her own health also influenced maternal rating of child health. CONCLUSION: The results do not support the persistence of a vulnerable child syndrome, as health in infancy does not affect maternal rating of current child health at school-age in the absence of current health problems. PMID- 8361792 TI - Understanding of acquired immunodeficiency syndrome by elementary school children -a developmental survey. AB - OBJECTIVES: The developmental process by which young children acquire an understanding of the concepts of causality, treatment, and prevention of illness as related to acquired immunodeficiency syndrome (AIDS) is poorly understood. Previous studies have focused on adolescent populations and have measured the facts that children seem to know rather than their understanding of relevant concepts. Such approaches are likely to overestimate the child's true level of understanding and obscure significant misconceptions. The aims of this project are to measure directly the level of understanding of the concepts of causality, treatment, and prevention of AIDS in healthy, elementary school children and to assess the sociodemographic variables associated with their conceptual understanding. METHODS: Using a new, developmentally based, semistructured interview protocol (ASK, AIDS Survey for Kids), 361 children (57% black, 24% Hispanic, 19% white) in kindergarten through sixth grade at four public schools in New Haven, CT were interviewed. Responses to questions about causality, treatment, and prevention were scored for each of three illnesses (AIDS, and for comparison, colds and cancer) based on the level of conceptual sophistication of the response, irrespective of its factual accuracy. RESULTS: Scores for each of the concepts were highly intercorrelated and were correlated most strongly with grade level (R = .31 to .50, P < .0001 for each of these correlations, with the exception of the treatment of AIDS). Gender, race, and socioeconomic status did not contribute significantly to the variance observed for any of the concept scores in a linear regression model. Over-all, children's level of understanding of causality was significantly less sophisticated for AIDS than for colds (P < .0001); their level of conceptual understanding for the causality of AIDS was not significantly different from that of cancer (P = .9). CONCLUSIONS: Children's understanding of causality, treatment, and prevention of AIDS, as measured by the ASK, follows the same developmental sequence reported for children's understanding of general physical illness. Sociodemographic variables, such as race, gender, and socioeconomic status do not affect children's level of sophistication of these developmental concepts. These results have implications for the creation of developmentally appropriate and effective AIDS education curricula for primary and elementary grades. They also offer guidance to health care providers in their efforts to educate parents and young children about this important topic. PMID- 8361793 TI - Endotracheal administration of tolazoline in hypoxia-induced pulmonary hypertension. AB - STUDY OBJECTIVE: To compare the pulmonary and systemic vascular responses to intravenously (IV) and endotracheally (ET) administered tolazoline (Tz) in newborn lambs with hypoxia-induced pulmonary hypertension. DESIGN: Randomized, controlled study design. METHODS: Twenty lambs, 2 to 7 days of age, were anesthetized, intubated, and surgically catheterized for continuous physiologic monitoring and cardiac output measurements using radiolabeled microspheres. After a postoperative stabilization period, the lambs were ventilated with a hypoxic gas mixture which was titrated to increase mean pulmonary artery pressure (MPAP) 30% to 50% above baseline. Each animal was randomly assigned to receive either IV Tz (2 mg/kg), ET-Tz (4 mg/kg), or ET-saline (Sal, control group). RESULTS: ET-Tz significantly (P < .05) reduced MPAP, PVRI (pulmonary vascular resistance index), MPAP/mean artery pressure (MAP) and PVRI/systemic vascular resistance index (SVRI), but not SVRI. IV-Tz lowered (P < .05) MPAP, PVRI, and PVRI/SVRI but also produced significant reductions in MAP and SVRI while only transiently decreasing MPAP/MAP: MPAP/MAP and PVRI/SVRI ratios were consistently lower in the ET-Tz animals than either the IV-Tz or ET-Sal animals. CONCLUSIONS: Our results suggest that ET-Tz produced a more selective pulmonary vascular response than IV-Tz and may warrant further investigation for potential clinical applications. PMID- 8361794 TI - Feeding iron-fortified premature formula during initial hospitalization to infants less than 1800 grams birth weight. AB - OBJECTIVE: A randomized, double-blind study was conducted comparing high-iron content (15 mg/L) with low-iron content (3 mg/L) premature formula given during initial hospitalization to infants with birth weights less than 1800 g to determine the influence of these differing intakes on the iron nutritional status during the first 4 months of life. A third group of similar infants received human milk mixed with an equal volume of liquid fortifier resulting in an iron content of approximately 1.7 mg/L. PATIENTS AND METHODS: Mean birth weight, gestational age, age at study entry, volume of blood removed for studies, and volume of red cells transfused were not different among the three groups. After hospitalization both formula-fed groups were given a cow milk formula with an iron content of 12 mg/L, and breast-fed infants were given an iron-containing multivitamin with a resulting iron intake of 10 mg/d. Infants were observed to 8 weeks after discharge. RESULTS: There were no differences in serum iron, ferritin, transferrin, transferrin saturation, hemoglobin, hematocrit, or reticulocyte count among the three groups at study entry, although mean corpuscular hemoglobin and mean corpuscular volume were lower in infants in the low-iron formula group. Mean plasma ferritin was significantly lower in infants receiving low-iron content premature formula at the time of hospital discharge compared with the other two groups. The incidence of anemia (hemoglobin < 9.0 g/dL) and low transferrin saturation (< 24%) was also greater in the low-iron content formula group. Eight weeks after discharge, the incidence of low plasma ferritin (< 19 ng/mL) remained greater in infants receiving low-iron content formula than in the other two groups. No adverse effects of iron intake were observed. Growth was not different among the three groups. CONCLUSIONS: These data indicate that preterm infants with < 1800 g birth weight receiving premature infant formula benefit from formula given during initial hospitalization containing 15 mg/L iron compared with that containing 3 mg/L. PMID- 8361795 TI - Effects of repeated application of emollient cream to premature neonates' skin. AB - OBJECTIVE: Emollient cream moisturizers are often used on premature newborns in neonatal intensive care units without accurate knowledge of the risks or benefits to the neonate. DESIGN: We prospectively compared premature neonates treated with a water-in-oil emollient cream for up to 16 days to untreated premature neonates. SETTING: The study was completed in a neonatal intensive care unit on neonates admitted for respiratory distress and/or possible sepsis. PATIENTS: Thirty-four neonates, between 29 and 36 weeks estimated gestational age, entered the study. INTERVENTIONS: One-half of the neonates were treated twice a day with an water-in oil emollient cream, and the other half served as controls. OUTCOME MEASURES: The skin condition of the neonates' hands, feet, and abdomen was evaluated on entering the study and twice a week. Fungal cultures and quantitative bacterial cultures were obtained from the axilla and abdomen on entering the study and twice a week. RESULTS: The mean gestational age of the treated neonates was 32.3 weeks, whereas the mean gestational age of the control neonates was 32.5 weeks. The neonates treated with emollient cream demonstrated statistically less dermatitis of their hands (day 2 through day 11), their feet (day 2 through day 16), and their abdomen (day 7 through day 11). Fungal cultures and quantitative bacterial cultures of the abdomen and axilla were equivalent in both groups. CONCLUSIONS: These studies document that emollient cream moisturizer therapy of premature neonates decreases dermatitis without changing the microbiological flora. PMID- 8361796 TI - Desmopressin acetate and nocturnal enuresis: how much do we know? AB - OBJECTIVES: Desmopressin acetate (DDAVP) is promoted to treat nocturnal enuresis but indications for its use are unclear. We reviewed all randomized controlled trials to determine (1) short- and long-term efficacy, (2) responders, (3) dose response curve, (4) side effects, and (5) comparative efficacy with other treatments. METHODS: A Medline search of the English language literature from January 1966 to August 1992, supplemented by contact with the drug companies, yielded 18 articles which were true randomized controlled trials (11 cross-over and 7 parallel studies). RESULTS: The 18 randomized controlled trials included 689 subjects for most of whom some other type of treatment had failed. All studies found decreased mean frequency of wetting ranging from 10% to 91%, but only 24.5% of subjects achieved short-term dryness. One study of DDAVP responders directly tested long-term dryness and 21% stayed dry. In three studies that incidentally reported on long-term effects 5.7% stayed dry after stopping DDAVP: There was wide variation in the type of patient included. Seven studies addressed prognostic factors. Children more than 9 years old and with fewer initial wet nights do better. Four studies seem to include almost exclusively monosymptomatic children with nocturnal enuresis (ie, primary nocturnal enuresis, positive family history, and no urinary symptoms). Results were no better than those which included mixed symptoms. Five studies attempted to address the dose-response issue. Despite some methodological issues, there is probably some dose-response effect. Side effects were infrequent in the 589 subjects who received DDAVP as opposed to placebo. No cases of water intoxication and no significant shifts in electrolytes were reported in the four studies which measured them. Nasal stuffiness, headache, epistaxis, and mild abdominal pain seem to be the only side effects noted, and these were uncommon. Only one study compared DDAVP with conditioning alarms. Alarm patients had 10% fewer wet nights and a better long term result. CONCLUSIONS: DDAVP reduces wet nights in children for whom other treatments have failed but it produces complete dryness in a minority, and this is often a temporary effect. The literature focuses on short-term efficacy. The true role of DDAVP will be known when samples are carefully selected, prognostic factors are examined, and more comparisons with other treatments are conducted focusing on long-term outcomes. On the basis of current knowledge, DDAVP is inferior to conditioning alarms as a primary therapy. PMID- 8361797 TI - Head-upright tilt table testing in children with unexplained syncope. AB - Recurrent syncope in the young patient can be an anxiety-provoking experience that is often difficult to diagnose. Head-upright tilt table testing has emerged as a method for provoking episodes of vasodepressor syncope in predisposed individuals and thereby establishing a diagnosis. Currently indicated in the evaluation of young patients with recurrent unexplained syncope, it has also proven useful in differentiating convulsive syncope from epilepsy. Further studies will be needed to better define its role in the evaluation and management of recurrent syncope in children and adolescents. PMID- 8361798 TI - Significance of serial C-reactive protein responses in neonatal infection and other disorders. AB - OBJECTIVE: This study was performed to determine prospectively whether, in the presence of proved or presumed bacterial infection, the sensitivity of serum C reactive protein (CRP) response could be enhanced by serial rather than single determinations. We also sought to assess CRP responses to clinically identified noninfectious disorders. DESIGN: The CRP responses of 491 infants on 691 occasions of suspected infection were assessed. CRP levels were measured initially and twice again at 12-hour intervals (rate immunonephelometry). Assessments also included a blood culture, complete blood cell count, and chest radiograph and culture of spinal fluid when appropriate. CRP responses were correlated with four designated clinical groups: (1) positive blood or cerebrospinal fluid cultures (n = 190); (2) negative blood culture-definite infection (necrotizing enterocolitis stages 2 and 3, pneumonia, subcutaneous abscess) (n = 52); (3) negative blood culture-possible infection (antenatal risk factors, meconium aspiration, positive urine group B streptococcus antigen, necrotizing enterocolitis stage 1, febrile infants) (n = 287); and (4) negative blood culture-no infection (respiratory distress syndrome, transient tachypnea of the newborn, patent ductus arteriosus, tissue trauma) (n = 160). Diagnoses were made before CRP results were known. RESULTS: In all, 187 (27%) of the blood cultures were positive. A single organism was recovered from 174 of these; two organisms from 13. Among the single-organism cultures, 50 (29%) were Gram negative, 120 (69%) were Gram-positive, and 4 (2%) were budding yeasts. CRP levels were elevated in various groups as follows: in the positive blood culture group (by organism), Gram-negative rods, 92% (46/50); group B streptococcus, 92% (12/13); Staphylococcus aureus, 89% (8/9); group D streptococcus, 71% (10/14); Streptococcus viridans, 60% (6/10); Staphylococcus epidermidis, 55% (40/73). In the negative blood culture-definite infection group, CRP levels were abnormal in 88%; in the negative culture-possible infection group, CRP was elevated in 33%; and in the negative blood culture-no infection group, CRP was elevated in 9%. Serial determinations of CRP resulted in enhanced sensitivity in the positive blood culture group, the negative blood culture-definite infection group, and the negative blood culture-possible infection group. Initial determinations by themselves were inadequately sensitive. Serial determinations did not enhance sensitivity of the negative blood culture-no infection group. High specificity (91%) is suggested by the low incidence of abnormal CRP levels among infants who were not infected. CONCLUSIONS: These data suggest that it would be appropriate to conduct a cautious, controlled trial to assess the safety of discontinuing antibiotic therapy if three serial CRP measurements are normal and if there are no other clinical factors suggestive of infection. The data also indicate the necessity for serial determinations of CRP for optimal sensitivity. PMID- 8361799 TI - Factors influencing the interests, career paths, and research activities of recent graduates from an academic, pediatric residency program. AB - OBJECTIVE: This study was undertaken to characterize the professional activity of a cohort of young pediatricians who completed an academically oriented residency program, to analyze factors which influenced their interests, career choices, and research activity, and to understand what steps might be effective in attracting more young physicians into academic and research career paths. METHOD: We studied by questionnaire a cohort of 150 pediatric residents from the Children's Hospital in Boston who completed residency training between 1976 and 1981. RESULTS: Questionnaires were returned by 117 (78%) of 150 individuals. Of these, 73% were in academic medicine and 37% were in clinical practice. Individuals were engaged in various activities with a mean of 47% effort in clinical care, 25% effort in administration and teaching, and 28% effort in basic or clinical research. The majority of respondents (71 [61%] of 117) reported at least 10% effort in all three activities. Only 9 (8%) of 117 reported no clinical activity, 8 (7%) of 117 reported no teaching or administrative activity, and 35 (30%) of 117 reported no research activity. Few individuals dedicated more than 50% of their time to research, and none reported a 100% commitment to research. Clinical sources provided 71% of all salary support, research grants 17%, government salaries 7%, and other sources 5%. For most respondents, interest in clinical practice predated medical school, whereas interest in research increased during preclinical training, particularly among those who engaged in research activities. Respondents identified previous research experience as the principle factor enhancing their decision and ability to do research. Factors that adversely influenced their decision or ability to do research included salary expectancy, funding, the perceived competitiveness of academic life, administrative duties, and family responsibilities. CONCLUSIONS: Efforts to encourage more young physicians to enter academic careers should focus on providing research experience during preclinical training and providing long-term support for research which enables physician scientists to maintain their interest and involvement in clinical medicine. PMID- 8361800 TI - Should chloral hydrate be banned? AB - OBJECTIVE: Current federal regulations of potentially carcinogenic environmental chemicals are based on the assumption that risks for humans can be extrapolated from the effects of chronic high-dose exposure of rodents. It is assumed that all chemicals induce cancer by a genotoxic mechanism (direct interaction with DNA) and that humans metabolize chemicals by the same pathways as the test rodents. Trichloroethylene, a former medicine, is now regulated because of rodent studies. Its major metabolite, chloral hydrate, widely used as a sedative in both adults and children, is in danger of being banned by comparable studies. This paper assesses the safety of chloral hydrate. DESIGN: Analysis of the literature regarding the metabolic, toxicologic, and epidemiologic data on trichloroethylene and chloral hydrate. RESULTS: The dose-response relationship for carcinogenesis of chloral hydrate and other chemicals in its metabolic breakdown pathway is nonlinear in rodents: very high doses given chronically, sufficient to cause cellular necrosis, are necessary for induction of malignancies. In addition, epidemiologic data on people exposed to substantial amounts of trichloroethylene (which is metabolized to chloral hydrate) show no increase in mortality or cancers. CONCLUSIONS: The assumptions underlying current regulatory practices for environmental chemicals are not applicable to the medicinal use of chloral hydrate. Instead, a threshold model is appropriate. The data do not suggest the need to ban chloral hydrate as a medicine; however, possible modifications in its use are suggested. PMID- 8361801 TI - Nosocomial Legionella pneumonia in the neonate. PMID- 8361802 TI - Linea vestibularis: follow-up of a normal genital structure. PMID- 8361803 TI - Turner syndrome with unusual conotruncal defect. PMID- 8361804 TI - Suprapubic aspiration of urine in very low birth weight infants. PMID- 8361805 TI - Acute flank pain and reversible renal dysfunction associated with nonsteroidal anti-inflammatory drug use. PMID- 8361806 TI - Adverse effect of chloral hydrate in two young children with obstructive sleep apnea. PMID- 8361807 TI - Cigarette smoke = radiation hazard. PMID- 8361808 TI - The treatment of nocturnal enuresis--where are we now? PMID- 8361809 TI - New series of essays on pediatric history. PMID- 8361810 TI - Conception and creation of the American Academy of Pediatrics. PMID- 8361811 TI - American Academy of Pediatrics Committee on Drugs and Committee on Environmental Health: Use of chloral hydrate for sedation in children. PMID- 8361812 TI - American Academy of Pediatrics Committee on Fetus and Newborn: Routine evaluation of blood pressure, hematocrit, and glucose in newborns. PMID- 8361813 TI - American Academy of Pediatrics Committee on Pediatric Emergency Medicine: First aid for the choking child. PMID- 8361814 TI - American Academy of Pediatrics Committee on Infectious Diseases: Haemophilus influenzae type b conjugate vaccines: recommendations for immunization with recently and previously licensed vaccines. PMID- 8361815 TI - American Academy of Pediatrics Committee on Early Childhood, Adoption, and Dependent Care: The pediatrician's role in promoting the health of patients in early childhood education and/or child care programs. PMID- 8361816 TI - American Academy of Pediatrics Committee on Genetics: Folic acid for the prevention of neural tube defects. PMID- 8361817 TI - American Academy of Pediatrics Section on School Health: Residency training and continuing medical education in school health. PMID- 8361818 TI - Resident education in school health: an issue whose time has come. PMID- 8361819 TI - American Academy of Pediatrics Committee on School Health. Guidelines for the administration of medication in school. PMID- 8361820 TI - American Academy of Pediatrics Committee on Infectious Diseases: Use of ribavirin in the treatment of respiratory syncytial virus infection. PMID- 8361821 TI - Lead poisoning: twenty years after. PMID- 8361822 TI - Passive tobacco exposure and sudden infant death syndrome. PMID- 8361823 TI - Passive tobacco exposure and sudden infant death syndrome. PMID- 8361825 TI - The lead controversy. PMID- 8361824 TI - Ceftriaxone for otitis media. PMID- 8361826 TI - The lead controversy. PMID- 8361827 TI - Neuroendocrine effects of toxic and low blood lead levels in children. PMID- 8361828 TI - Temporal constraints on apparent motion in auditory space. AB - The hypothesis that the extent of spatial separation between successive sound events directly affects the perception of time intervals between these events was tested using an apparent motion paradigm. Subjects listened to four-tone pitch patterns whose individual tones were sounded alternately at one of two loudspeaker positions, and they adjusted the alternation rate until they could no longer distinguish the four-tone ordering of the pattern. Four horizontal and two vertical loudspeaker separations were tested. Results indicate a direct relation between horizontal separation and the critical stimulus onset asynchrony (SOA) between successive tones within a pattern. At the critical SOA, subjects reported hearing not a four-tone pattern, but two pairs of two-note groups overlapping in time. The findings are discussed in the context of auditory spatial processing mechanisms and possible sensory-specific representational constraints. PMID- 8361829 TI - Perception of local shape from shading. AB - Theoretically, metric solid shape is not determined uniquely by shading. Consequently, human vision has difficulty in categorizing shape when shading is the only cue. In the present research, subjects were required to categorize shaded quadric surfaces. We found that they were rather poor at this task; they confused hyperbolic and elliptic (both convex and concave) shapes easily. When a cast shadow visually indicated the direction of the illuminant, they were able to notice the concavity or convexity of elliptic shapes. However, they still confused elliptic and hyperbolic ones. Finally, when an animated sequence of eight intensity patterns belonging to one quadric shape had been displayed, the subjects were able to categorize the quadrics. However, the results are still quite moderate. Our experiments indicate that local shading structure is only a weak shape cue when presented in the absence of other visual cues. PMID- 8361830 TI - Recovery of 3-D shape from binocular disparity and structure from motion. AB - Four experiments were conducted to examine the integration of depth information from binocular stereopsis and structure from motion (SFM), using stereograms simulating transparent cylindrical objects. We found that the judged depth increased when either rotational or translational motion was added to a display, but the increase was greater for rotating (SFM) displays. Judged depth decreased as texture element density increased for static and translating stereo displays, but it stayed relatively constant for rotating displays. This result indicates that SFM may facilitate stereo processing by helping to resolve the stereo correspondence problem. Overall, the results from these experiments provide evidence for a cooperative relationship between SFM and binocular disparity in the recovery of 3-D relationships from 2-D images. These findings indicate that the processing of depth information from SFM and binocular disparity is not strictly modular, and thus theories of combining visual information that assume strong modularity or independence cannot accurately characterize all instances of depth perception from multiple sources. PMID- 8361831 TI - Haptic identification of objects and their depictions. AB - Haptic identification of real objects is superior to that of raised two dimensional (2-D) depictions. Three explanations of real-object superiority were investigated: contribution of material information, contribution of 3-D shape and size, and greater potential for integration across the fingers. In Experiment 1, subjects, while wearing gloves that gently attenuated material information, haptically identified real objects that provided reduced cues to compliance, mass, and part motion. The gloves permitted exploration with free hand movement, a single outstretched finger, or five outstretched fingers. Performance decreased over these three conditions but was superior to identification of pictures of the same objects in all cases, indicating the contribution of 3-D structure and integration across the fingers. Picture performance was also better with five fingers than with one. In Experiment 2, the subjects wore open-fingered gloves, which provided them with material information. Consequently, the effect of type of exploration was substantially reduced but not eliminated. Material compensates somewhat for limited access to object structure but is not the primary basis for haptic object identification. PMID- 8361832 TI - Counterexample to the hypothesis of functional similarity between tactile and visual pattern perception. AB - In earlier work, the author has demonstrated that tactile pattern perception and visual pattern perception exhibit many parallels when the effective spatial resolution of vision is reduced to that of touch, thus supporting the hypothesis that the two pattern senses are functionally similar when matched in spatial bandwidth. The present experiments demonstrate a clear counterexample to this hypothesis of functional similarity. Specifically, it was found that the lateral masking effect of a surround on tactile character recognition increases when the surround changes in composition from solid lines to dots, whereas for vision, recognition performance goes in the opposite direction. This finding necessitates some modification of the model of character recognition proposed by the author (Loomis, 1990) as it applies to the sensing of raised tactile patterns. One possible modification would be to incorporate, as the initial stage of pattern transformation, the continuum mechanics model for the skin that was developed by Phillips and Johnson (1981b). PMID- 8361833 TI - Additivity of loudness across critical bands: a critical test. AB - The use of magnitude estimation as well as axiomatic measurement theory has led to the suggestion that loudness adds across critical bands. In the present paper, we challenge this postulate by applying a more sensitive methodology, based on Falmagne's (1976) random conjoint measurement procedure. A necessary condition for additivity of loudness was investigated in tone complexes consisting of 2-kHz and 5-kHz (resp. 3-kHz) components; the results showed systematic deviations from additivity. We argue that these deviations are due to asymmetric masking of the higher component by the lower one, and we propose a tentative quantitative model to account for the data. Such a model is in line with results from tone-on-tone masking, which show masking to be effective over a range of several critical bands. PMID- 8361834 TI - Response selection, sensitivity, and taste-test performance. AB - Tasters selected the odd stimulus from among sets of three samples of party dip. Two samples came from one batch, and one sample came from another batch. The physicochemical difference between the batches consisted of the presence or absence of added salt. Two different tests of discriminability were undertaken by the same subjects with the same stimuli: the triangle test and the three alternative forced-choice (3-AFC) method. Although different numbers of correct selections were obtained in the two tasks, an index of discriminability, d', had the same value when the data were analyzed in accordance with the Thurstone-Ura and signal-detection models, respectively. The average data support Frijters's (1979b) contention that different models of the discrimination process are appropriate to the results of the triangular and the 3-AFC procedures. Further analysis of the data revealed that discrimination was poorer for trios containing one physicochemically weak stimulus and two stronger stimuli than it was for trios containing one stronger stimulus and two weak stimuli. A two-signal 3-AFC task was undertaken by some subjects, and d' estimates from this task were lower than expected on the basis of performance in the other tasks. PMID- 8361835 TI - Alternating prism exposure causes dual adaptation and generalization to a novel displacement. AB - In two experiments, we examined the hypothesis that repeatedly adapting and readapting to two mutually conflicting sensory environments fosters the development of a separate adaptation to each situation (dual adaptation) as well as an increased ability to adapt to a novel displacement (adaptive generalization). In the preliminary study, subjects alternated between adapting their visuomotor coordination to 30-diopter prismatic displacement and readapting to normal vision. Dual adaptation was observed by the end of 10 alternation cycles. However, an unconfounded test of adaptive generalization was prevented by an unexpected prism-adaptive shift in preexposure baselines for the dual-adapted subjects. In the primary experiment, the subjects adapted and readapted to opposite 15-diopter displacements for a total of 12 cycles. Both dual adaptation and adaptive generalization to a 30-diopter displacement were obtained. These findings may be understood in terms of serial reversal learning and "learning to learn." PMID- 8361836 TI - Limits on the limitations of context-conditioned effects in the perception of [b] and [w]. AB - We investigated the conditions under which the [b]-[w] contrast is processed in a context-dependent manner, specifically in relation to syllable duration. In an earlier paper, Miller and Liberman (1979) demonstrated that when listeners use transition duration to differentiate [b] from [w], they treat it in relation to the duration of the syllable: As syllables from a [ba]-[wa] series varying in transition duration become longer, so, too, does the transition duration at the [b]-[w] perceptual boundary. In a subsequent paper, Shinn, Blumstein, and Jongman (1985) questioned the generality of this finding by showing that the effect of syllable duration is eliminated for [ba]-[wa] stimuli that are less schematic than those used by Miller and Liberman. In the present investigation, we demonstrated that when these "more natural" stimuli are presented in a multi talker babble noise instead of in quiet (as was done by Shinn et al.), the syllable-duration effect emerges. Our findings suggest that the syllable-duration effect in particular, and context effects in general, may play a more important role in speech perception than Shinn et al. suggested. PMID- 8361837 TI - Viewing behavior: ocular and attentional disengagement. AB - In five experiments, we examined the role of the ocular and attentional systems in determining saccadic latencies. Prior to making a saccade to a target stimulus, subjects were required to direct their attention to a foveal stimulus or to an eccentric stimulus. Either stimulus could be extinguished before the onset of the target. Saccadic latencies were shortest when the foveal stimulus was extinguished, regardless of whether it was attended or not. Control experiments showed that subjects were able to attend properly and that warning, arising from turning off a stimulus before target onset, could not completely account for the results. The results were discussed in terms of ocular disengagement, attentional disengagement, and joint ocular-attentional disengagement. It was concluded that an explanation emphasizing ocular disengagement provided the best account of the data. PMID- 8361838 TI - Stereo-motion cooperation and the use of motion disparity in the visual perception of 3-D structure. AB - When an observer views a moving scene binocularly, both motion parallax and binocular disparity provide depth information. In Experiments 1A-1C, we measured sensitivity to surface curvature when these depth cues were available either individually or simultaneously. When the depth cues yielded comparable sensitivity to surface curvature, we found that curvature detection was easier with the cues present simultaneously, rather than individually. For 2 of the 6 subjects, this effect was stronger when the component of frontal translation of the surface was vertical, rather than horizontal. No such anisotropy was found for the 4 other subjects. If a moving object is observed binocularly, the patterns of optic flow are different on the left and right retinae. We have suggested elsewhere (Cornilleau-Peres & Droulez, in press) that this motion disparity might be used as a visual cue for the perception of a 3-D structure. Our model consisted in deriving binocular disparity from the left and right distributions of vertical velocities, rather than from luminous intensities, as has been done in classical studies on stereoscopic vision. The model led to some predictions concerning the detection of surface curvature from motion disparity in the presence or absence of intensity-based disparity (classically termed binocular disparity). In a second set of experiments, we attempted to test these predictions, and we failed to validate our theoretical scheme from a physiological point of view. PMID- 8361839 TI - Organizational factors and the perception of motion in depth. AB - When two stationary, stereoscopically separated targets are viewed in a completely dark surround, and no cues concerning their egocentric distances from the observer are salient, the farther target tends to be seen at the same distance it would have assumed if it were by itself. The nearer target is seen as being closer than it would have been if seen alone. The present studies extend this previous finding (now termed the far-anchor effect) into the domain of targets that move in stereoscopic space. Observers viewed two small illuminated targets, which began at either the same or different stereoscopic distances. One of the targets was moved in depth and the observers identified the target that appeared to move. Conditions varied according to the initial depth location of the moving target. Significantly more correct responses were reported when the nearer target moved than when the farther one moved, consistent with the hypothesis that the perception of motion in depth is affected by the aforementioned perceptual anchoring effect of the farther target. PMID- 8361840 TI - Visual angle as a determinant of perceived interobject distance. AB - Two new experiments and a reanalysis of Toye's (1986) data are used to examine the relationship between true distance and perceived distance in natural scenes. In the first experiment, 8 subjects estimated 78 interobject distances, formed by all pairs of 13 objects, while viewing the objects from a fixed position. The results showed that estimated distance is a linear function of the visual angle between objects as well as of the true distance. This relationship results in distances perpendicular to the line of sight being overestimated in relation to true distances and to distances parallel to the line of sight. These findings were confirmed by reanalysis of a comparable data set from Toye. Since changes in the visual angle can come about through changes in alignment with the line of sight, viewing distance, or interobject distance, Experiment 2 was designed to determine whether the visual angle effect was due to one of these, or whether it was an independent effect. In Experiment 2, 8 subjects estimated six interobject distances from 12 viewing positions. The results showed that visual angle predicted estimated distance independently of how the change in visual angle came about, suggesting that the greater the visual angle between objects, the more their separation is overestimated. PMID- 8361841 TI - What are human express saccades? AB - When a fixation point is removed 200 msec prior to target onset (the gap condition), human subjects are said to produce eye movements that have a short latency (80-120 msec), that form the early peak of a bimodal latency distribution, and that have been labeled "human express saccades" (see, e.g., Fischer, 1987; Fischer & Breitmeyer, 1987; Fischer & Ramsperger, 1984, 1986). In three experiments, we sought to obtain this express saccade diagnostic pattern in the gap condition. We orthogonally combined target location predictability with the presence versus absence of catch trials (Experiment 1). When target location was fixed and catch trials were not used, we found mostly anticipations. In the remaining conditions, where responses were under stimulus control, bimodality was not frequently observed, and, whether it was or not, latencies were not in the express saccade range. Using random target locations, we then varied stimulus luminance and the mode of stimulus presentation (LEDs vs. oscilloscope) in the gap and overlap (fixation is not removed) conditions (Experiment 2). Bimodality was rarely observed, the gap effect (overlap minus gap reaction time) was additive with luminance, and only the brightest targets elicited saccades in the express range. When fixed locations and no catch trials were combined with latency feedback (Experiment 3), we observed many responses in the express saccade range and some evidence for bimodality, but the sudden introduction of catch trials revealed that many early responses were not under stimulus control. Humans can make stimulus-controlled saccades that are initiated very rapidly (80 120 msec), but unless catch trials or choice reaction time is used, it is not possible to distinguish such saccades from anticipatory responses that are prepared in advance and timed to occur shortly after target onset. Because the express saccade diagnostic pattern is not a characteristic feature of human saccadic performance, we urge investigators to focus their attention on the robust gap effect. PMID- 8361842 TI - Henry Bence Jones: the best chemical doctor in London. PMID- 8361843 TI - Public hospitals--past, present, and future. PMID- 8361844 TI - Regulation of the acute phase response by cytokines. AB - Cytokines appear to function as part of a complex regulatory network, a signaling language in which informational content resides in the combinations, and perhaps sequence, of cytokines and other extracellular messenger molecules received by a cell. The effects of combinations of cytokines are complex and often differ from their in vitro effects or when administered by themselves. (From this perspective, to use a somewhat crude simile, individual cytokines can be thought of as words which bear informational content. Although individual cytokines may, on occasion, communicate a complete message, more commonly the actual messages received by cells probably resemble sentences, in which it is the combination and sequence of words which convey information.) Currently available data suggest an in vivo scenario in the acute phase response in which the hepatocyte receives a complex mixture of humoral or paracrine signals which are integrated by multiple interacting post-receptor and gene regulatory mechanisms to cause finely regulated changes in plasma protein synthesis. Regulation often occurs by transcriptional control, but post-transcriptional mechanisms, including translational regulation, may participate. Both the extracellular and intracellular mechanisms that mediate the response of the hepatocyte to inflammatory stimuli appear to be highly complex and involve multiple overlapping, concurrent, and parallel pathways. Enough is known at present to conclude that IL-6 is a major participant in these changes in man. Regulation of non-hepatocyte acute phase phenomena has not been delineated as thoroughly, but clearly involves a number of cytokines. PMID- 8361845 TI - Physician distinguish thyself: conflict and covenant in a physicians' moral development. PMID- 8361846 TI - Progesterone: the forgotten hormone? PMID- 8361847 TI - Arsenic, an old case: the chronic heavy metal poisoning of Raphaelle Peale (1774 1825). PMID- 8361848 TI - The trials and tribulations of George Miller Sternberg (1838-1915)-- America's first bacteriologist. PMID- 8361849 TI - Dental services under New Mexico Medicaid. PMID- 8361850 TI - Commentary on freedom of movement. PMID- 8361852 TI - Specialisation in nursing. Nursing education vis-a-vis trends towards specialisation. PMID- 8361851 TI - Defense styles and choice of nursing career among women. PMID- 8361853 TI - Protecting, promoting and supporting breast feeding: the special role of maternity services. PMID- 8361854 TI - Low cost aids for teaching science subjects in nursing institutions. PMID- 8361855 TI - Equating nursing education with allied professions. PMID- 8361856 TI - Protecting, promoting and supporting breast feeding: the special role of maternity services. PMID- 8361857 TI - Evaluation of continuing education programmes in nursing. PMID- 8361858 TI - Anatomy of an antibody, and related misadventures in developing an effective treatment for septic shock. PMID- 8361860 TI - Understanding and treating dyslipidemia associated with noninsulin-dependent diabetes mellitus and hypertension. AB - Hypertension and diabetes appear to increase coronary heart disease risk in part by causing an abnormality in lipid metabolism. Most affected are patients with familial dyslipidemic hypertension (FDH) and noninsulin-dependent diabetes mellitus (NIDDM). The lipid disorders most often encountered in these patients are increased levels of triglycerides, very low-density lipoprotein (VLDL) cholesterol, and small, dense low-density lipoprotein (LDL) cholesterol, and low levels of high-density lipoprotein (HDL) cholesterol. These abnormalities appear to result from increased hepatic secretion of VLDL particles due to increased concentrations of free fatty acids and glucose, reduced VLDL clearance due to reduced activity of lipoprotein lipase, and reduced LDL clearance due to glycosylation of ligand proteins. Treatment of the dyslipidemia associated with FDH should follow the guidelines from the National Cholesterol Education Program. Treatment in men and women with NIDDM should be considered when LDL cholesterol levels are 130 mg/dl or above, triglyceride levels are 200 mg/dl or above, or non HDL cholesterol levels are 160 mg/dl or greater. Aggressive lifestyle changes should be initiated first, including weight loss in obese patients, control of glucose levels in those with NIDDM, avoidance of antihypertensive drugs that may worsen lipid levels in patients with FDH, and eating a diet restricting saturated fat and cholesterol. Addition of lipid-altering drugs should be considered if such changes do not achieve effective lipid control. The agent should be tailored to the patient's lipid profile, in general by using bile acid resins, niacin, or reductase inhibitors to lower LDL cholesterol and gemfibrozil or niacin to lower triglycerides. Niacin should be avoided in patients with NIDDM. PMID- 8361859 TI - The role of Helicobacter pylori in peptic ulcer disease. AB - The pathophysiology of peptic ulcer disease (PUD) is often described as an imbalance between aggressive factors such as acid and pepsin and alterations in the mucosal protective mechanisms. Helicobacter pylori is a gram-negative organism that has been identified as a potential causative agent in the pathogenesis of PUD. The exact mechanism by which it contributes to mucosal damage is unknown. It is thought that the organism may disrupt the protective mucous layer, allowing the underlying epithelium to be injured by gastric acid. Significant evidence indicates that H. pylori is a major etiologic factor in type B gastritis. Data confirming its etiologic role in duodenal ulcer (DU) disease is not conclusive; however, eradication of the organism is associated with a reduction in the recurrence of DU. Optimum therapy to eradicate H. pylori has not been established, although several multidrug regimens have been evaluated. Treatment of H. pylori infection should be reserved for individuals in whom conventional therapy for DU is unsuccessful and those whose ulcers relapse during maintenance therapy. PMID- 8361861 TI - Liver disorders in patients receiving chlorpromazine or isoniazid. AB - Based on information derived from computers and clinical records obtained from general practitioners in the United Kingdom, we estimated the frequency of liver toxicity associated with two known hepatotoxins, chlorpromazine and isoniazid. Among the cohort of 10,502 users of chlorpromazine, 14 had illnesses compatible with drug-induced liver disease, a frequency of 1.3/1000 users (95% Cl 0.8, 2.2). Four presumed cases of the disorder occurred among 921 users of isoniazid, for a frequency of 4/1000 users (95% Cl 1.7, 11.1). This study provides population based quantification of the frequency of liver disorders associated with the use of these two agents. PMID- 8361862 TI - Differences in serum concentrations of and responses to generic verapamil in the elderly. AB - STUDY OBJECTIVE: To determine if there are greater differences in bioavailability of generic verapamil at steady state in elderly patients than in healthy young subjects. DESIGN: Double-blind, randomized, three-way crossover study. SETTING: Clinical research center at a general teaching hospital. SUBJECTS: Eight young, healthy subjects between ages 18 and 45 years, and eight elderly, hypertensive patients over 65 years of age. INTERVENTIONS: Each participant was randomly assigned to receive brand-name verapamil or one of two generic preparations. Young subjects received each of the three preparations 80 mg twice/day for 7 days separated by a 1-week washout. Elderly patients took the three preparations for 21 days. Serum drug levels and blood pressure were measured and electrocardiograms performed 13 times after the last dose of drug. MAIN RESULTS: In young subjects, the pharmacokinetics and pharmacodynamics of the three preparations were nearly identical. There was, however, a great deal of variability in the bioavailability of the generic products. In the elderly patients, one generic product had a maximum serum concentration and area under the curve that were 77% and 43% greater, respectively, than the brand-name product (p < 0.02). Assessments of bioequivalency (based on confidence intervals) demonstrated that this generic drug's bioavailability was from 4-118% and peak serum concentration from 10-139% greater than the brand-name drug. This was associated with greater prolongation of the PR intervals. CONCLUSIONS: A generic verapamil product that is bioequivalent in young subjects may not be bioequivalent in elderly subjects. Testing of drugs with complex pharmacokinetics in young subjects may not reliably predict the clinical outcomes in elderly hypertensive patients. PMID- 8361863 TI - Zidovudine pharmacokinetics in HIV-positive women during different phases of the menstrual cycle. AB - STUDY OBJECTIVE: To examine the pharmacokinetics of zidovudine during the menstrual cycle in human immunodeficiency virus- (HIV-) positive women. DESIGN: Open, unblinded study. SETTING: A women's clinic for acquired immunodeficiency syndrome (AIDS) at a large medical center. PATIENTS: HIV-positive women with a CD4+ cell count above 200/mm3, receiving long-term zidovudine therapy, with a history of regular menstrual cycles. INTERVENTIONS: All patients received a 100 mg dose of zidovudine in the fasted state on three occasions. MEASUREMENTS AND MAIN RESULTS: Zidovudine and zidovudine-glucuronide plasma concentrations were measured with radioimmunoassay to determine the pharmacokinetic characteristics during each menstrual phase. The drug's mean peak plasma concentrations (range 233-808 ng/ml) were 556 +/- 145, 385 +/- 132, and 495 +/- 143 ng/ml during the menstrual, late follicular-ovulatory, and luteal phases, respectively. Initially, plasma concentrations declined in a linear fashion from 0 to 4 hours, with a prolonged elimination phase in many patients after 4 hours. The mean zidovudine area under the curve was 886 +/- 156, 845 +/- 268, and 775 +/- 167 ng.hour/ml. The mean percentage of dose recovered was 44.2 +/- 26.0, 56.9 +/- 19.1, and 42.2 +/- 16.6, respectively. CONCLUSIONS: The pharmacokinetics of zidovudine were not different during the three phases of the menstrual cycle; however, considerable intrapatient and interpatient variability was noted for many of the values. PMID- 8361864 TI - Relationship between pain severity and serum beta-endorphin levels in postoperative patients. AB - STUDY OBJECTIVE: To examine the relationship among postoperative pain severity, serum beta-endorphin level, and serum morphine level in pediatric patients after posterior spinal fusion with instrumentation. DESIGN: A prospective study. SETTING: University-based medical center. PATIENTS: Ten patients age 13-17 years admitted for posterior spinal fusion with instrumentation. INTERVENTIONS: Each subject was administered an initial dose of intravenous morphine 100 micrograms/kg, followed by a constant infusion of 50 micrograms/kg/hour. The primary physician was allowed to titrate the dosage as required to meet the patient's requirement for analgesia. Whole blood was obtained for the analysis of serum morphine and beta-endorphin levels preoperatively, after the initial morphine dose, 24 hours after initiation of the infusion, and before any change in dosage. At each blood sampling time, pain severity ratings were obtained from the subject, nurse, and parent using a 10-point linear scale. MEASUREMENTS AND MAIN RESULTS: No statistical difference between serum beta-endorphin values preoperatively and after the initial dose of morphine was observed; mean values were 68 and 60 pg/ml, respectively. The relationships between serum beta endorphin level and pain scores were statistically significant only for self (subject) pain scores (p = 0.014, r = 0.30). Mean serum morphine level was 21.9 ng/ml for patients with self pain scores of 4 or less. CONCLUSION: The clinical usefulness of serum beta-endorphin as a measure of pain severity was not established under the experimental conditions of this study. PMID- 8361865 TI - Influence of hyperbaric oxygen on the pharmacokinetics of single-dose gentamicin in healthy volunteers. AB - STUDY OBJECTIVE: To determine the single-dose pharmacokinetics of gentamicin in healthy humans undergoing hyperbaric oxygen (HBO) exposure. DESIGN: Randomized, crossover trial. SETTING: Specialized hyperbaric research facility within a United States Air Force medical center. SUBJECTS: Five healthy men between 28 and 43 years of age. INTERVENTIONS: Each subject received a total of two doses of intravenous gentamicin 1.5 mg/kg lean body weight spaced at least 2 weeks apart. One dose was infused under normobaric oxygen (NBO) conditions and the other under HBO conditions. MEASUREMENTS AND MAIN RESULTS: Gentamicin pharmacokinetic values were determined on 11 serum samples per subject collected sequentially out to 300 minutes after infusion. Using PCNONLIN, the following results demonstrated no difference between the pharmacokinetic values under HBO and NBO conditions, respectively: beta half-life (112, 115 min); volume of distribution (0.201, 0.184 L/kg); peak concentration (6.52, 7.23 mg/L); clearance (0.0754, 0.0676 L/kg/hr). CONCLUSIONS: Hyperbaric oxygen produced no changes in the measured pharmacokinetic values of gentamicin under the conditions specified in this study. It is possible that numerous HBO exposures could produce a cumulative effect on gentamicin pharmacokinetics that would not be discernible in a single dose study. Because of the profound physiologic effects of HBO, drugs with narrow therapeutic indexes should be evaluated under HBO conditions if they are to be given to patients receiving HBO treatments. PMID- 8361866 TI - Evaluation of transdermal theophylline pharmacokinetics in neonates. AB - Theophylline may be administered by several routes, but problems are associated with neonatal dosing. The transdermal route may provide a safer and noninvasive method of administration, yet produce therapeutic concentrations in a consistent and reliable manner. To study the feasibility of this in the apnea of prematurity, stable neonates were administered a subtherapeutic transdermal dose for 24 hours in order to assess pharmacokinetics and bioavailability. This was followed with routine intravenous theophylline therapy according to institutional policy. Six of nine neonates had detectable serum theophylline concentrations that increased slowly after patch application. Mean (+/- SD) maximum serum concentration was 2.4 +/- 1.3 micrograms/ml, mean time to maximum serum concentration was 22 +/- 8.2 hours, and mean latency period was 8.0 +/- 4.9 hours. Mean total amount of theophylline delivered to the skin was 18.6 +/- 4.1 mg. Mean fractional absorption at 30 hours was 0.25 +/- 0.12. These data demonstrate that it is possible to produce systemic theophylline concentrations with a transdermal patch in preterm infants sufficient to study pharmacokinetics and bioavailability, and that transdermal delivery of therapeutic doses is technologically feasible. PMID- 8361867 TI - Patterns of acetaminophen use in alcoholic patients. AB - Alcoholics may be predisposed to the hepatotoxicity of acetaminophen due to increased activity of the cytochrome P-450 system and decreased hepatic glutathione. To date, scattered case reports provide only a brief sketch of the frequency and pattern of acetaminophen use by alcoholics. To determine these variables, we obtained a detailed ethanol and drug history from patients answering yes to at least one of four questions on the CAGE questionnaire. Patients were classified in terms of their acetaminophen use as nonusers, users as necessary, or regular users. Regular users were further classified as nondaily or daily users, or abusers (> 4 g/day). A total of 64 patients were enrolled in the study. The average number of positive responses to the CAGE questionnaire was 3.27 +/- 0.91. Of the 64 patients, 34 (53.1%) were continuous daily drinkers, 28 (43.8%) binge drinkers, and 2 (3.1%) had completely discontinued using alcohol. By history, 32 (50)% were nonusers of acetaminophen. Of the 32 users, 12 (37.5%) stated they took it as needed and 20 (62.5%) took it regularly. Of the 20 regular users, 7 (35%) were nondaily users, 11 (55%) were daily users, and 2 (10%) were abusers. Approximately 31% of alcoholics used acetaminophen regularly, most on a daily basis, with 1 of every 10 abusing the drug. Of the 64 alcoholics interviewed, 3 (4.7%) fit the drinking and acetaminophen use patterns theoretically associated with hepatotoxicity. PMID- 8361868 TI - Institution-specific patterns of infection and Gram's stain as guides for empiric treatment of patients hospitalized with typical community-acquired pneumonia. AB - STUDY OBJECTIVE: To determine the appropriateness of cefazolin as empiric treatment of typical, as opposed to atypical, bacterial community-acquired pneumonia at our institution. DESIGN: Combination of retrospective chart review and prospective determination of microbial susceptibilities and cefazolin associated cost savings. SETTING: General acute-care referral hospital. PATIENTS: We evaluated the charts of patients discharged with a diagnosis of community acquired pneumonia over a 10-year period. Gram's stains and culture results of sputum samples processed over 2 months were analyzed to determine the ability of the stains to predict positive Haemophilus influenzae cultures. The susceptibility and beta-lactamase status of clinical isolates of H. influenzae were determined. Cost savings of cefazolin as empiric treatment for community acquired pneumonia were evaluated. MEASUREMENTS AND MAIN RESULTS: The frequency of H. influenzae pneumonia at our institution was 15% of the three major bacterial community-acquired pneumonias. Gram's stain was highly accurate in predicting the presence or absence of Haemophilus sp in sputum. Five patients had positive outcomes with cefazolin treatment despite being diagnosed with H. influenzae pneumonia. The organism isolates demonstrated intermediate sensitivity to cefazolin and 85% were beta-lactamase negative. Our program that encourages empiric use of cefazolin over cefuroxime for typical bacterial community-acquired pneumonia has allowed a modest projected annual cost savings of $24,000. CONCLUSIONS: We concluded that when Gram's stain of sputum does not show Haemophilus sp in patients with typical bacterial community-acquired pneumonia, empiric treatment with cefazolin is appropriate and results in cost savings. PMID- 8361869 TI - Potentially serious drug interactions secondary to high-dose diltiazem used in the treatment of pulmonary hypertension. AB - Two patients had potentially serious drug interactions (phenytoin, digoxin) that were probably attributable to changes in pharmacokinetics and pharmacodynamics caused by high-dose calcium channel blocker therapy (diltiazem) in the treatment of pulmonary hypertension. Even in the approved normal dosages for the treatment of angina and hypertension, calcium channel blockers are known to cause significant changes in the metabolism of other drugs. Currently, no data exist on the effects of the very high dosages of these drugs, administered to patients with pulmonary hypertension, on the metabolism and clearance of other agents, although, based on our experience and literature reports, recommendations for monitoring therapy can be made. PMID- 8361870 TI - Can garlic lower blood pressure? A pilot study. AB - A popular garlic preparation containing 1.3% allicin at a large dose (2400 mg) was evaluated in this open-label study in nine patients with rather severe hypertension (diastolic blood pressure > or = 115 mm Hg). Sitting blood pressure fell 7/16 (+/- 3/2 SD) mm Hg at peak effect approximately 5 hours after the dose, with a significant decrease in diastolic blood pressure (p < 0.05) from 5-14 hours after the dose. No significant side effects were reported. Our results indicate that this garlic preparation can reduce blood pressure. Further controlled studies are needed, particularly with more conventional doses (e.g., < or = 900 mg/day), in patients with mild to moderate hypertension and under placebo-controlled, double-blind conditions. PMID- 8361871 TI - Development and implementation of simplified aminoglycoside empiric dosing guidelines. AB - Poor empiric dosing of aminoglycosides continues to be a problem in many hospitals. Consequently, a two-phase study was undertaken to evaluate gentamicin and tobramycin (G-T) dosing in our institution and to develop practical guidelines to achieve optimum initial G-T serum concentrations. In the pre intervention phase (phase 1), approximately one-third of 232 G-T treatment courses were initiated with regimens that resulted in low initial serum concentrations. Empiric dosing guidelines were subsequently developed using Pharmacy Pharmacokinetic Service data and literature recommendations. They were validated with patients in phase 1. Compared with earlier dosing methods, the guidelines resulted in initial serum G-T concentrations within the therapeutic range in an equivalent proportion of patients. To simplify the procedure, recommended dosages were based on age, total weight, and serum creatinine only. The guidelines were tabular in format, and prescriber calculations were not required. Pocket and wall chart guidelines were distributed and promoted. During the post-intervention phase (phase 2), the impact of the guidelines was assessed. A review of 232 phase 1 and 203 phase 2 treatment courses revealed an increase in the initial mean dose per interval prescribed after the intervention (p < 0.01). No change in the mean interval was noted. When guidelines were followed, a higher proportion of treatment courses achieved early therapeutic serum concentrations (Cpmax 5-10 mg/L, 80% vs 54%; p < 0.005). The new empiric guidelines appear to be a practical alternative to existing methods of dosing aminoglycosides. PMID- 8361872 TI - [Circadian rhythm of blood pressure and pulse rate in young men with diabetes mellitus type I depending on duration of disease]. AB - In order to investigate the blood pressure-heart rate interrelation and their circadian pattern in type I diabetes mellitus, we performed ambulatory blood pressure monitoring in 28 normotensive patients without clinical nephropathy divided in two groups. Group A consisted of 14 males with short-term DM (mean 2 years, mean age 28 +/- 6 years), group B consisted of 14 males with long-term DM (mean 12 years, mean age 31 +/- 7 years). Ambulatory blood pressure monitoring revealed significantly higher night heart rate in B group (74 +/- 13 l/min vs. 62 +/- 11 l/min in A, p < 0.01) and day diastolic blood pressure (83 +/- 9 mm Hg vs. 74 +/- 8 mm Hg in A, p < 0.01) and night diastolic blood pressure (73 +/- 10 mm Hg vs. 62 +/- 8 mm Hg in A, p < 0.01). The linear regression SBP/HR equation were significantly different (p < 0.02) (HR = 0.48 x SBP + 21, r = 0.40 in A vs. HR = 0.29 x SBP + 69, r = 0.28 in B). We concluded that type I diabetes duration has significant influence on diastolic blood pressure and heart rate even in patients without diabetic nephropathy and could be related to changed sensitivity of the baroreceptors. PMID- 8361873 TI - [Levels of insulin in serum during fasting and circadian blood pressure profile in young health men]. AB - In order to investigate the relation of ambulatory blood pressure values to fasting plasma insulin, non-invasive 24-hour blood pressure monitoring was performed in 32 young normotensive males. Systolic and diastolic blood pressures were averaged for awake and asleep periods. Fasting plasma insulin levels correlated significantly with both asleep (r = 0.61; p < 0.001) and awake systolic blood pressures (r = 0.44; p < 0.02) but not with casual systolic blood pressure (r = 0.27). There were no significant associations of awake, asleep and causal diastolic blood pressures values with fasting plasma insulin levels (r = 0.15, 0.05 and 0.21, respectively). These results support the hypothesis that insulin may be a physiological determinant of blood pressure. PMID- 8361874 TI - [Indices of left heart ventricle relaxation after 5-months of hypotensive therapy with guanfacine]. AB - The subject of the work is to assess the clinical parameters and diastolic function in patients with mild or moderate essential hypertension after 5-month treatment with guanfacine 0.5-3 mg/day, mean 1.7 mg. In the group there were 8 women and 8 men, mean age 53.7 +/- 7.6. The diastolic function of the left ventricle was assessed from the echocardiographic M-mode paper sweep of the left ventricle by the method of Gibson and Brown. In clinical parameters systolic, diastolic and mean blood pressure was found to decrease significantly, the heart rate was unchanged. Essential improvement of the markers of relaxation was received while amelioration of filling was not significant. The before treatment data were compared with the similar ones of the 60 persons of the control group. The significant differences were found in values of blood pressure, markers of relaxation and indices Iv and Ip. PMID- 8361875 TI - [Enalapril in patients with diabetes mellitus type I with microalbuminuria without hypertension]. AB - The studies included 18 normotensive patients with diabetes mellitus type I (mean age 29 years) and constant microalbuminuria (UAE-30 - 300 mg/24 hours). Group A consisted of 10 patients treated with enalapril, and group B--10 patients given placebo. Glomerular filtration rate, ERPF, and UAE were measured before and after 6 months of therapy. UAE decreased significantly in patients of group A (p = 0.02) after 6 months while evident proteinuria was seen in two patients of group B. Arterial blood pressure dropped in patients of group A (131/84 vs 122/78 mm Hg), and increased significantly in patients of group B (126 +/- 8 vs 136 +/- 15 mm Hg; p < 0.05). Blood flow through kidneys improved (p = 0.02) and renal vascular resistance decreased (p = 0.02) in patients of group A. The obtained results suggest that enalapril may prevent diabetic nephropathy in diabetics with constant microalbuminuria. PMID- 8361876 TI - [Principles of hypotension treatment in patients with diabetes]. AB - Epidemiological studies have revealed, that elevated blood pressure is in diabetics 1.5-3.0-times more frequent that in general population. It is one of the most important factors increasing the morbidity and mortality due to small and big arteries disease. Hypotensive therapy should be commenced in diabetic persons earlier than in patients without diabetes mellitus. In many such diabetic patients blood pressure normalization could be obtained by dietary adaptations and metabolic compensation. In more advanced cases pharmacological treatment should be undertaken. When selecting the drug for a diabetic person one has to balance between positive and adverse actions. The drugs of the first choice are the ACE inhibitors, drugs blocking the slow calcium channel and alpha 1 adrenergic receptors, because they do not influence negatively the carbohydrate and lipid metabolism. On contrary, prazosin and ACE inhibitors increase the tissue sensitivity to insulin. The latter group decrease also intraglomerular pressure and albuminuria. As a routine the treatment begins with small, testing dose of a single hypotensive drug. The dosage may be increased slowly up to the average dose level. If this manipulation does not permit normalization of blood pressure one may combine 2 or 3 hypotensive drugs. Selection of the drug and of its dose rely also on the type and intensity of late diabetic complications--at first nephropathy and autonomic neuropathy. PMID- 8361877 TI - [Level of glycosylated hemoglobin in children with newly diagnosed diabetes during their hospitalization]. AB - Percent of HbA1 was determined in 60 children with newly diagnosed diabetes mellitus at the beginning and end of their first hospitalization. High levels of HbA1 (over 15%) were found in the majority of children at the admittance which means late diagnosis. A decrease in HbA1 by 0.5-7.5% was noted in 76% of all diabetic children treated at the hospital for 7-24 days. In 54% out of these children HbA1 levels decreased by 1.5-4.5%. Mean HbA1 value was 3.6% following a two-week hospitalization, and 3.7%--after 3 weeks. Mean decrease in HbA1 for all treated children was 0.18% per week. Positive correlation between HbA1 and its percentage and mean glycaemia at the beginning of hospitalization was seen. No correlation between HbA1 values measured at the end of hospitalization and blood glucose levels determined during the whole hospitalization period was found. PMID- 8361878 TI - [Zinc plasma and erythrocyte levels in insulin dependent diabetes]. PMID- 8361879 TI - [Effect of nonselective beta-adrenergic blockade on blood plasma levels of glucagon in plasma during insulin-induced hypoglycemia]. AB - An effect of nonselective beta-adrenergic blockade with propranolol on the blood plasma level of glucagon during insulin-induced hypoglycemia was studies in 20 control dogs and 20 alloxan diabetic dogs. Increased sensitivity to exogenous insulin and prolonged hypoglycemia were noted during nonselective beta-adrenergic blockade. However, glucagon response to insulin-induced hypoglycemia following propranolol administration was increased. PMID- 8361880 TI - [Incidence of the most important metabolic disorders in the population of a little town in Poland]. AB - The study aimed at establishing a risk for metabolic diseases in the randomly selected population in the age over 18 years, inhabitants of the little town in Siedlce Voivodeship. Using comparative tables, in was found that percent of women and men in the investigated group is similar to that in the population of this town. Women prevailed slightly in the investigated group which characterized also relatively low age (42 years) and low diastolic blood pressure. Obesity was found in 40% of the investigated subjects. Over 2.6% had diabetes mellitus and 11.4%- improper glucose tolerance (according to WHO criteria). Every fifth subject has blood lipids disorders. Such disorders were more frequent in the subgroup of men. Additionally, relationships between these findings were analysed. Body weight index markedly correlated with blood triglycerides level and less pronounced with blood total cholesterol and uric acid. Negative correlation between BMI and HDL cholesterol levels was noted. The lack of correlation between glycaemia, cholesterolemia and triglyceridemia results from the fact that there is such a correlation in men but not in women. The obtained results indicate the necessity of preventive measures. PMID- 8361881 TI - [Dynamics of growth and glucose uptake in cultured human fibroblasts collected from patients with diabetes mellitus, type 2]. AB - Dynamics and glucose uptake in the human fibroblasts cultures were investigated for 14 days. Fibroblasts were taken from 16 patients with diabetes mellitus type 2 and 8 patients adjusted with age but with no history of diabetes mellitus. It was found that diabetic fibroblasts grew much slower than controls and reached the stationary phase later. Glucose uptake in both groups of fibroblasts- measured as the diminishment of glucose levels in the medium every two days--did not differ markedly in the phase of the rapid proliferation whereas was significantly higher in the stationary phase in the cultures of diabetic fibroblasts in comparison with the controls. It may thus assumed that diabetic fibroblasts reveal abnormal glucose metabolism in addition to reported intracellular disorders in protein, nucleic acids, lipids, collagen, and glycosaminoglycans synthesis. PMID- 8361882 TI - [Osteoporosis in insulin dependent diabetes]. AB - A case of female patient with non-compensated diabetes mellitus is presented. Pathological bone fractures caused by the diabetic osteoporosis were produced in the relatively short period of time. An emphasis is on the role of pathogenetic factors leading to the diabetic osteoporosis, prevention and treatment of this disease are discussed. PMID- 8361883 TI - [Renin-angiotensin system in diabetes mellitus]. PMID- 8361884 TI - [Determination of blood glucose values with glucostix]. AB - The study involved 214 patients of both sexes, including those treated at the Institute of Oncology in Gliwice and children treated for diabetes mellitus at the Diabetic++ Out-Patient Clinic in Gliwice. Blood glucose was assayed with GLUKOZA EO kit manufactured by POCh and strip test Glucostix (visually and with reflectance meter Glucometer II Ames). In case of blood glucose assays with strip tests a deviation of +/- 25% of the determined value was considered as a difference which does not affect diagnostic value. Blood glucose concentration determined visually with Glucostix test is similar or lower than that found in the laboratory. Moreover, the use of reflectance meter does not improve diagnostic value of an assay. PMID- 8361885 TI - [Full assortment of national preparations of insulin places Poland foremost among world producers]. PMID- 8361886 TI - [Basal and reactive renin and aldosterone secretion in arterial hypertension of insulin dependent diabetics]. AB - The aim of the study was to assess the significance of the renin-angiotensin aldosterone system (R-A-A) in the pathogenesis of arterial hypertension in patients with diabetes type I (IDDM). Testing was accomplished in the hospital conditions in a group of 131 patients with long-term IDDM, who beside of diabetes mellitus and its chronic complications did not show any symptoms of additional diseases. The patients were divided in 5 groups (A-E) depending on the type of coexisting late diabetic complications. The control group was consisted of 20 healthy persons matched for sex and age. In each case the following tests were performed: measurement of blood pressure in succumbent position, daily profile of glycemia and glucosuria, Hb A1 level, ophthalmoscopy, functional assessment of kidney and autonomic system status. Tenin activity in plasma (ARO) and plasma aldosterone (ALD) were determined in basal (after 6 h of succumbent position) and after i.v. administration of 40 mg of furosemide and 3 h of standing position (reactive values). In all groups under study the significant decrease of average, basal and reactive ARO was found in comparison with the control group. This abnormality was the most distinct in subjects with diabetic nephropathy. The autonomic neuropathy was abolishing this tendency. The mean concentration ob basal ALD was in all diabetic subgroups similar as in the controls. The mean reactive ALD was however significantly decreased. In diabetes complicated by retinopathy the negative correlation between ARO and systolic, diastolic and mean blood pressure existed. In diabetes complicated by nephropathy the dependence between blood pressure and ARO and ALD was not found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361887 TI - [Role of the EDRF system--that is, nitric oxide--in vasodilation]. PMID- 8361888 TI - [The effect of blood pressure changes during hemodialysis on left ventricular systolic function]. AB - Echocardiographic study was performed in 31 uremic patients on maintenance hemodialysis (HD) with no apparent heart failure, valvular heart disease, pericardial effusion or coronary artery disease. On the basis of blood pressure patients were classified into two groups: 1) patients with normal arterial pressure (group I) (n = 19), 2) patients with blood hypertension (group II) (n = 12). Cardiac function was assessed immediately before and after HD session. Left ventricular end-diastolic diameter (EDD), left ventricular end-systolic diameter (ESD) and ejection fraction (EF) were calculated. Body weight, heart rate and mean blood pressure (mBP) were also measured. A significant decrease of EDD was noted in both groups during HD but it was less evident in group II (p < 0.05). ESD decreased significantly in group II (p < 0.01) when it did not change in group I. EF increased significantly only in group II (p < 0.05). Blood pressure decreased during HD in both groups. A significant inverse linear association between EF and ESD was noted during HD in both groups (r = -0.685; p < 0.001) but was more evident in group II. There was no association between and EDD (r = 0.199; NS). Similar analysis shows that ESD was significantly with mBP (group II- r = 0.914; p < 0.001, group I--r = 0.565; p < 0.05). Such association were not found for EDD and RR. Only in group II the decrease in mBP was statistical significantly correlated with the increase in EF. The decrease in EDD during HD exists probably due to changes in intravascular volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361889 TI - [Early and late results of simultaneous and multiple artificial valve replacement in patients with multiple heart valve defects]. PMID- 8361891 TI - [Exercise tolerance in children with primary bicuspid valve prolapse syndrome]. AB - Exercise tolerance in children with the primary bicuspid valve prolapse syndrome has been evaluated with ergometric test. Additionally, an effect of environmental factors on exercise tolerance has been assessed in children from the urban and rural areas. A good tolerance of submaximal loads has been shown in both groups. However, the obtained results have been significantly more favourable in children from rural areas. The authors have concluded that limitation of exercise in children with bicuspid valve prolapse is not necessary during an intensive growth. PMID- 8361890 TI - [Effect of treatment with vasodilators on physical exercise tolerance in patients with chronic congestive heart failure]. AB - The studies were performed in 46 patients with chronic congestive heart failure (CCHF), III and IV NYHA classes. During the first two weeks all patients received digoxin (D) and furosemide (F) in optimal doses (stage O). Then, patients were randomly divided into two groups. During the stage A group I (n = 26) received digoxin, furosemide and nifedipine (N), while in the stage B captopril (K) was added to that treatment and it was continued for 4 weeks. During the following two weeks (stage C) patients were treated the same as in stage A. During the same stages group II (n = 20) received D, F and isosorbide dinitrate (S), then, D, F, S and K followed by D, F and S, respectively. After the termination of each stage of the treatment all patients performed physical exercise on bicycle ergometer, until limiting symptoms have occurred. Power (M) and duration (t) of exercise, systolic (ps) and diastolic (Pd) arterial blood pressures, heart rate (HR) at the peak load, and HR x Ps and HR/M indices were determined. It was found that N did not significantly affect the investigated ergometric parameters. Combined treatment with D, F, N and K induced an increase in M, t and HR, and a decrease in. This effect persisted through the stage C. Following the treatment with D, F and S, a significant increase in M and decrease in HR/M were observed. Addition of K to D, F, and S did not induce further improvement in the physical exercise tolerance of these patients. PMID- 8361892 TI - [Certain characteristics of myocardial infarction in young patients as compared with those over 65 years old]. AB - Death rate due to myocardial infarction shows constantly growing tendency, especially in young subjects. This fact is even referred to as overmortality of young and middle-aged men. The aim of the present study was to evaluate certain clinical elements of myocardial infarction in young subjects. Out of 668 patients with acute myocardial infarction treated at the I Cardiac Department in Cracow from 1979 to 1988 a group of 102 patients (5 women, 97 men) below 45 years of age (mean = 40) was selected. The control group consisted of 241 patients with myocardial infarction, including 146 men and 98 women over 65 years of age (mean = 73). The following clinical date were analyzed: sex, presence of retrosternal pain and its aggravation, time from the onset of pain to hospitalization, anginal pain preceding the infarction and such complication as sudden cardiac arrest, pulmonary edema, cardiogenic shock, in-hospital deaths. The infarction in patients below 45 years of age occurred mainly in men. They experienced retrosternal pain more frequently than the elderly patients. It did not, however, affect the time of hospitalization. Serious complications of the infarction developed less frequently in younger patients and the in-hospital mortality was also lower in that group. PMID- 8361893 TI - [Type of behavior pattern and risk factors in young men after myocardial infarction]. AB - The studies involved 102 male patients, aged between 23 and 40 years, with a history of one myocardial infarction. Behaviour pattern was determined with The Jenkins Activity Survey questionnaire. Total serum cholesterol, triglycerides, glucose, and uric acid concentrations were assayed, both diastolic and systolic blood pressures were measured, all patients were weighed, and reported the number of smoked cigarettes. A mean number of risk factors per patient was calculated as well as their incidence in various behaviour patterns. It was found behaviour pattern A predominates in young male patients with a history of myocardial infarction. However, serum total cholesterol, triglycerides, and uric acid levels were lower in this group in comparison with those representing behaviour patterns B and X. The authors suggest that behaviour pattern A may be an independent risk factor for myocardial infarction in young subjects. Further studies are, therefore, needed within the programs of circulatory diseases prevention. PMID- 8361894 TI - [New outlook on aldosterone]. PMID- 8361895 TI - [Therapeutic effectiveness of molsidomine in patients with exercise-induced angina pectoris]. AB - Exercise tolerance was tested with cycloergometer, and ECG recorded in 33 patients with exercise-induced angina pectoris. Patients' age ranged from 36 to 65 years. Tests were performed prior to and after a single oral dose 2 mg of molsidomine or placebo. Molsidomine reduced the number of patients with exercise induced coronary pain from 33 to 25, i.e. from 84.5% to 27.27%. Pain-free period was significantly longer in patients given molsidomine whereas postexercise pain and total duration of the coronary pain were significantly shorter. Total work was markedly higher, and maximum ST depression in ECG record following exercise was significantly lower than the values noted prior to molsidomine administration and in placebo group. Heart rates both resting and during exercise did not differ in molsidomine and placebo groups. Molsidomine may be considered as an effective drug preventing exercise-induced anginal pain within 1 hour after administration. PMID- 8361896 TI - [Hemolysis after bioprosthesis implantation in the mitral valve]. AB - Rare case of hemolysis following an implantation of the biological mitral valve is presented. In 1985, biological mitral valve of Ionescu-Shiley type was implanted to a 45-year female patient for post-rheumatic mitral defect. Patient was in the III NYHA class before surgery. Her health status improved after operation. Several echocardiographic examinations have shown normal functioning of the implanted valve (normal gradient across the valve, no retrograde wave). Upper respiratory infection with subsequent progressive weakness, anemia, yellow skin, and heart failure occurred in 1991. Echocardiography has shown significant increase (twice) in the gradient across the valve (max 26, mean--14 mm Hg) and retrograde wave of the II degree as well as mitral insufficiency of the II degree. Laboratory tests have shown marked anemia with reticulosis, increase in blood bilirubin, increase in LDH activity (by about ten times), and a decrease in haptoglobins. Mitral valve dysfunction with hemolysis has been diagnosed. Patient was reoperated. Intraoperatively, incompletely healed valvular ring, and lesions to the leaves such as: fibrosis, thickening and partial deficits. Biological mitral valve was replaced with Corin-Carbotest artificial valve. Postoperative course was uncomplicated. PMID- 8361897 TI - [Selective ablation of slow conduction pathway in a patient with atrioventricular nodal reentrant tachycardia]. AB - In a 42-year female with paroxysmal atrioventricular nodal reentrant tachycardia of the type I (slow/fast) verapamil did not prevent it. Verapamil injections terminated tachycardia but marked hypotonia followed. Electrophysiologic study revealed dual conduction pathway within the atrioventricular node that made the substrate for reentrant tachycardia. An effective refractory period od the slow conduction pathway in antegrade direction was less than 220 msec. An effective refractory period of the fast pathway in antegrade and retrograde directions was 300 msec. Radiofrequency current ablation was performed at the site of slow pathway morphology electrogram recording. A single application of the radiofrequency current that lasted 40 sec. producing the maximum 60C successively ablated the slow pathway. Follow-up electrophysiologic study before and after atropine administration proved the success of this procedure. No other heart structures were damaged. A 4-month follow-up period did not show tachycardia. PMID- 8361898 TI - [Cardiac arrhythmias in patients with chronic congestive heart failure]. PMID- 8361899 TI - [Effect of anti-arrhythmia therapy on mortality of patients after myo cardial infarction]. PMID- 8361900 TI - [Reperfusion injury to the myocardium]. AB - Reperfusion injury is of increasing importance due to new techniques of restoring blood flow to acutely ischaemic areas by means of thrombolysis, angioplasty, or acute coronary artery bypass surgery. Reperfusion of ischaemic myocardium can results in the acceleration of surrounding reversibly injured myocytes and endothelial cells to irreversibly injured cells. The complex group of phenomena associated with reperfusion include: no-reflow, arrhythmias, "stunned" myocardium impaired contractile power and abnormalities of relaxation. Experimental studies have demonstrated that microvascular damage may play an important role in the pathogenesis of this phenomenon. The causal factors of reperfusion injury are not clarified, but include free radicals, calcium and various inflammatory mediators. The deleterious effects of reperfusion are related importantly to the action of oxygen-derived free radicals. These effects can be reduced or even prevented with scavengers of free radicals. However, the value of these agents in patients remains to be tested. Prophylactic chronic treatment of patients at high risk of coronary occlusion with a beta-adrenergic blocking agent or a calcium antagonist slow cell death causing limitation of infarct size. PMID- 8361901 TI - [Effect of heparin on the interaction between platelets with collagen]. AB - An effect of a standard heparin preparation on the interaction between blood platelets and collagen has been investigated. The experiments have shown, that the addition of heparin in the concentration of 0.3; 0.6 or 0.9 IU/mL did not change the interaction between blood platelets and collagen. Such interaction increased, when heparin concentration was 1,2 IU/mL, and remained unchanged despite the further increase in heparin concentration. The authors suggest that such a course of this interaction results from the stimulating action of heparin added in adequate concentration on protein release from platelet alpha granulations--which bound GP II b/III a complex with collagen. PMID- 8361902 TI - [Activation of the fibrinolytic system following subcutaneous administration and inhalation of heparin]. AB - Heparin was administered to 113 patients at risk of thrombosis classified to abdominal surgery either alone (subcutaneously or in inhalation) or in combination with anabolic steroid (nandrolone). No pharmaco-prophylaxis was used in 10 patients. On the day of surgery, heparin activated plasma fibrinolytic activity, prior to an introduction to anesthesia. Measurements of euglobulins clot lysis have shown an increase in endogenous fibrinolytic activity dependent and independent on Hageman's factor and an increase in exogenous fibrinolysis, tested after venous stasis was produced. Heparin had profibrinolytic activity, stimulating plasminogen activators in the blood plasma without the signs of hyperplasminemia. Fibrinolytic system response was the same following subcutaneous injection and heparin inhalations. Administration of heparin combined with anabolic steroid has no additional effect on plasma fibrinolytic activity. PMID- 8361903 TI - [Risk of alloimmunization in the granulocyte concentrate recipient]. AB - Forty five patients with diffused peritonitis, complicated with septic shock and neutropenia, have been analysed. Granulocyte concentrate has been administered to 25 patients with negative results of tests detecting lymphocytotoxic and leuko agglutinin antibodies. Such antibodies have been detected in 35.5% of all patients. These patients have not received granulocyte concentrate. During a 20 day follow up period, antibodies have been produced in 20% of granulocyte concentrate recipients. No signs of alloimmunisation have been noted in 49% of patients with severe peritonitis during the whole follow up period. Non-hemolytic symptoms after transfusions have been seen in 40% of granulocyte recipients and accompanied 16% of all transfusions. No correlation with the symptoms of alloimmunisation was noted. PMID- 8361904 TI - [Occurrence of antifibrinogen antibodies in serum of individuals diagnosed with serum sickness]. AB - Occurrence and antifibrinogen antibodies level have been determined in sera of 50 individuals with serum sickness and in 50 blood donors constituting the control group. Antifibrinogen antibodies have been detected in blood of 41 (82%) blood recipients. Titre of these antibodies have ranged from 1:8 to 1:512, and their agglutination potency has ranged from 5 to 67 Dunsford's units. Immediately after serum sickness diagnosis a decrease in both level and agglutination potency of these antibodies has been noted. Further treatment with full blood constantly increased both the level and agglutination potency of antifibrinogen antibodies. It is probable, that fibrinogen and its degradation products present in the given blood stimulated antibodies production. This hypothesis is fortified by the observation, that stable decrease in both the level and agglutination potency of antifibrinogen antibodies in patients with serum sickness treated with washed erythrocytes. Antifibrinogen antibodies of a titre ranging from 1:4 to 1:16, and agglutination potency of 5-18 Dunford's units have been detected in 14 blood donors constituting a control group. Specificity of the detected antifibrinogen antibodies as well as their IgG character have been also confirmed. PMID- 8361905 TI - [Fibrinolytic activity and tissue plasminogen activator level in healthy individuals prior to and after a ten-minute venous stasis]. AB - Fibrinolytic activity and tissue plasminogen activator (t-PA) level were measured in 33 healthy individuals prior to and after fibrinolytic system stimulation (i.e. a ten-minute venous stasis). Fibrinolytic activity was measured with the aid of euglobin lysis time, and lysis test on the fibrin plates (in own modification). Tissue plasminogen activator concentration was assayed spectrophotometrically with the COA-SET t-PA (Kabi Vitrum). No fibrinolytic activity of plasma specimens taken before the venous stasis was noted during fibrin lysis plate test whereas it was seen in 13 subjects after the venous stasis. Fibrinolytic activity of the plasma euglobins, measured as a surface on fibrin plates, increased significantly after the venous stasis in both sexes (by 35.5 mm2 on the average, i.e. by 51%). It was more marked in men than in women both prior to and after venous stasis (by 10.9% and 19.0%, respectively). A time of plasma euglobin lysis was shorter after venous stasis (by 110 minutes, on the average). There was no significant difference between the sexes. Tissue plasminogen activator concentration increased by 5.8 times (from 1.7 IU/ml to 9.9 IU/ml) after the stasis. Correlation between t-PA concentrations and fibrinolytic activity, measured on the fibrin plates, was highly positive. No such a correlation existed between t-PA concentrations and the time of euglobin lysis. The obtained results indicate variety of assessments of fibrinolytic system activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361906 TI - [Evaluation of phagocytic and bactericidal activities of neutrophils in peripheral blood of patients with anemia due to iron deficit]. AB - Phagocytic and bactericidal properties of neutrophils have been evaluated in 20 women with anemia due to iron deficit. Twenty healthy women in corresponding age and domicile served as a control group. No statistically significant difference in both phagocytic and bactericidal properties of peripheral blood neutrophils have been noted in both groups. A decrease in plasma bactericidal activity has been sen in patients with anemia due to iron deficit. It may be one of the causes of increased susceptibility to infections noted in patients with plasma iron deficit. PMID- 8361908 TI - [Reoperation of internal arterio-venous shunt for hemodialysis in children]. PMID- 8361907 TI - [Treatment of blood hyperviscosity syndrome with continuous plasma exchange using a Fenval CS 3000 separator in patients with multiple myeloma]. PMID- 8361909 TI - [Production of human anti-ferritin antibodies and RIA tests for determining ferritin in serum]. PMID- 8361910 TI - [Tissue plasminogen activator as a fibrinolytic agent]. PMID- 8361911 TI - [Autotransfusion--trials at intensification with erythropoietin]. PMID- 8361913 TI - [Hemolytic-uremic syndrome in children and adults]. PMID- 8361912 TI - [Sickle cell anemia--drepanocytosis]. PMID- 8361914 TI - Thinking it through. PMID- 8361915 TI - Two-year follow up of bipolar hemiarthroplasty. AB - Forty-seven bipolar hemiarthroplasties were performed from January 1985 to December 1986. Twenty-three patients (24 hips) returned for a history, physical, and repeat radiographs. Ten primary press-fit and two cemented primary bipolar hemiarthroplasties were performed. Four patients underwent cemented and eight received press-fit revision bipolar hemiarthroplasties. Fourteen patients had simultaneous cancellous, reamed femoral head autograft, or allograft acetabular bone augmentation. Omitting one patient who had replacement for Levi's pleonosteosis, the average acetabular migration among the remaining 23 patients was 4 mm of superior and 1.5 mm of medial progression. The mean modified d'Aubigne hip score was 33 for primary press-fit arthroplasty, 30 for primary cemented arthroplasty, 22 for press-fit revisions, and 32 for cemented bipolar revision arthroplasty. Morcellized bone graft tended to variably resorb with time. Among the press-fit stems, all but two patients complained of at least occasional thigh pain. All but one patient with primary press-fit hemiarthroplasty walked with a limp. We conclude that, although good early results can be obtained, significant number of patients will have groin and thigh pain. We have found no evidence either radiologically or clinically that nonstructural bone grafting with reamed femoral head will reliably incorporate or prevent further acetabular migration. PMID- 8361916 TI - Reflex sympathetic dystrophy in children: an orthopedic perspective. AB - To design diagnostic criteria for reflex sympathetic dystrophy (RSD) and to initiate a prospective treatment protocol, we reviewed our experience with 49 episodes of RSD in 36 children. There were 24 females and 12 males; mean age at diagnosis was 13.4 years (range: 8 to 19); mean time from pain onset to correct diagnosis was 9.2 months (range: 1 to 53). Lower extremity involvement predominated. Pain was "severe" in 61%, and skin color changes, swelling, hyperesthesia, abnormal skin temperatures, muscle weakness, and decreased range of motion were all present in at least 75% of cases. Osteopenia was observed in 15 of 38 radiographs; of 24 bone scans, 7 were normal, 11 showed increased uptake, and 6 demonstrated decreased uptake. Of the 23 children who had psychological evaluations, 83% revealed some type of significant emotional dysfunction. Analgesic and antiinflammatory medications were not helpful, nor were local injections or regional blockades effective. An inpatient diagnostic and rehabilitation program for treating chronic pain, including orthopedics, rheumatology, psychology, and twice-daily physical therapy was most likely to lead to resumption of age-appropriate activities. Despite extensive physiological testing, physician, parent, and/or patient reluctance to accept absence of a primary organic disease was common. We present diagnostic criteria for pediatric RSD. PMID- 8361917 TI - Obturator internus bursitis: a common factor in low back pain. AB - The presence of irritation of the obturator internus bursa (OIB) is identified as a common but thus far overlooked focus of myofascial irritability in association with low back pain. Eighteen of 50 consecutive patients with low back pain (36%) demonstrated the presence of tenderness at the anatomical site of the OIB. OIB was found in 11% of men and 43% of women. Nineteen of the 50 patients had regional myofascial pain; of these, eight (42%) had OIB tenderness. Palpation of the OIB will commonly reveal local tenderness in patients suffering from low back pain. In these patients, conservative treatment of regional myofascial disorders may be made more effective when therapy and/or local steroid injections are appropriately directed to the obturator internus bursa. PMID- 8361918 TI - The plight of the traumatic amputee. AB - This retrospective review of the long-term problems of patients with lower extremity amputation from trauma fails to support the opinion that most traumatic amputees do well. Overall, anatomic problems involved 51% of the amputees, and social problems involved 56%. Attempting limb salvage with subsequent secondary amputation did not seem to compromise the long-term outcome for these problems. The surgeon performing the amputation should try to obtain the best possible stump and insure that the patient gets the careful follow up and multidisciplinary team support needed to manage the anticipated problems. PMID- 8361919 TI - Scoliosis surgery in a steroid-dependent asthmatic. PMID- 8361920 TI - Factitious infections in orthopedic patients. PMID- 8361921 TI - Rupture of the brachial artery from closed posterior dislocation of the elbow in a wrestler. PMID- 8361922 TI - Stress fractures of the femoral neck following hardware removal from healed intertrochanteric fractures. PMID- 8361924 TI - Radiologic case study. Insufficiency fracture of the sacrum. PMID- 8361923 TI - The use of Dall-Miles cables in total hip arthroplasty. PMID- 8361925 TI - Is it bacterial or viral? Laboratory differentiation. AB - To differentiate viral, chlamydial, and mycoplasmal infections from bacterial disease in office and in emergency room practice, a combination of epidemiologic and clinical features usually will suggest one or a few microorganisms. Following that, laboratory diagnosis can be more targeted. Definition of the specific etiology will enable the proper management choice of antibiotics, antivirals, or symptomatic therapy. PMID- 8361926 TI - Sepsis in the newborn. PMID- 8361927 TI - The pediatrician's role in infant feeding decision-making. PMID- 8361928 TI - The acute management of paroxysmal supraventricular tachycardia in children. PMID- 8361929 TI - Nicotine dependence: diagnosis, chemistry, and pharmacologic treatments. PMID- 8361930 TI - Index of suspicion. Case 1. Acute epiglottitis. PMID- 8361931 TI - Index of suspicion. Case 2. Occult fracture. PMID- 8361932 TI - Index of suspicion. Case 3. Systemic lupus erythmatosus. PMID- 8361933 TI - Giardiasis. PMID- 8361934 TI - [Function of the pituitary-thyroid axis in chronic renal failure]. PMID- 8361935 TI - [Molecular basis of capacitation and acrosomal reaction]. AB - There has been described molecular events towards preparation of spermatozoa for fertilization as capacitation (process known to be characterized by increased mobility of membrane components on sperm surface) and acrosomal reaction (fusion of spermatozoon plasmalemma with outer acrosomal membrane with following destruction of acrosomal compartment and enzyme release). There have been also described hypotheses concerning activity of exposed during acrosomal reaction receptors for gamete binding and especially sperm receptors located on egg's zona pellucida. The role of acrosomal enzymes in penetration of zona pellucida by sperm as well as inhibition of enzymatic action were discussed in aspect of contraceptive potential. PMID- 8361936 TI - [Structure and function of LDL receptors in familial hypercholesterolemia]. AB - Structure and function of the LDL-receptor in genetic disorder--familial hypercholesterolemia is described as well as the structure of receptor coding gene. General outline of therapy in FH is also described. PMID- 8361937 TI - [Function, properties and clinical significance of n-acetyl-beta-D hexosaminidase]. AB - Function, tissue distribution and consequence of the inherited deficit of HEX A or HEX B, were described. The diagnostic value of the HEX determination in the renal diseases and diabetes, was reviewed. PMID- 8361938 TI - Thyroid dysfunction in the severely ill and elderly. Forget the classic signs and symptoms. AB - Manifestations of thyrotoxicosis and hypothyroidism are often ill-defined in elderly and seriously ill patients, and signs and symptoms may suggest a nonendocrine disease process instead. It is vitally important that physicians be aware of the possibility of thyroid disease in such patients. Failure to suspect the diagnosis may result in improper treatment and use of invasive diagnostic tests that not only fail to yield helpful results but also are potentially detrimental to the outcome. It is also essential to be able to distinguish between test abnormalities that indicate primary thyroid dysfunction and those that reveal an adaptive response to nonthyroidal illness. PMID- 8361939 TI - The facts about fibroids. Presentation and latest management options. AB - Uterine fibroids, which eventually develop in more than 50% of women, are usually asymptomatic, but they can cause many different symptoms and complications that challenge clinicians. For example, they can complicate pregnancy, mask the diagnosis of ovarian neoplasms, and confuse the management of menopause by causing abnormal uterine bleeding. The best noninvasive method of diagnosis is ultrasonography. Progestogens may be used to suppress menorrhagia, but use of these agents to treat fibroids is not routine. Gonadotropin-releasing hormone (GnRH) agonist analogues offer a promising medical approach to the treatment of fibroids; they have been shown to decrease fibroid size and to decrease uterine bleeding. Thus they may allow deferment of surgical treatment in selected patients (thereby preserving fertility) or decrease the risks involved when surgery is necessary. Further study is needed to assess the long-term effects of GnRH analogues on bone density, cholesterol levels, and risk of coronary artery disease. Surgical treatment is primarily by hysterectomy, unless myomectomy is indicated because of reproductive considerations. PMID- 8361940 TI - Your 'family doctor' may be a nurse! PMID- 8361941 TI - Helicobacter pylori and peptic ulcer disease. Reexamining the therapeutic approach. AB - Now that Helicobacter pylori has been strongly implicated as a causative factor in peptic ulcer disease, the dictum "no acid--no ulcer" may no longer be valid. However, H pylori has proved difficult to eradicate, and the approach to treatment of peptic ulcer is undergoing changes. At present, a triple-drug combination of bismuth and antibiotics is advised, and cultures should be obtained before and after treatment to monitor its efficacy. Side effects include pseudomembranous colitis and drug resistance. PMID- 8361942 TI - Congestive heart failure: today's approaches and tomorrow's directions. PMID- 8361943 TI - Noninvasive assessment of systolic and diastolic function. Important clues to differentiating types of congestive heart failure. AB - The clinical distinction between systolic and diastolic dysfunction as the cause for congestive heart failure (CHF) is readily made with noninvasive diagnostic testing. Patient history, physical examination, chest films, and electrocardiography provide readily obtainable clues to the presence of left ventricular dysfunction. Noninvasive imaging methods are an important quantitative adjunct in evaluation. Among these, echocardiography and radionuclide angiography are the most widely available and accepted techniques. Other advances, such as new radionuclide imaging agents, cine magnetic resonance imaging, and cine computed tomographic scanning, may also be useful in selected circumstances. Functional assessments using ventilatory gas analysis can aid in the evaluation of patients with CHF and in the timing of intervention with cardiac transplantation. PMID- 8361944 TI - Invasive testing in congestive heart failure. When is it useful? AB - Not only are findings from invasive studies in patients with congestive heart failure important for diagnosis, they may also be crucial in deciding on appropriate treatment and predicting prognosis. Hemodynamic evaluation may be useful for tailoring medical therapy, determining the need for mechanical support, predicting survival, deciding when valve surgery is needed, locating intracardiac shunts precisely, assessing the severity of pulmonary hypertension before cardiac transplantation, or diagnosing unexplained dyspnea. Contrast angiography can be used to evaluate systolic function if information from non invasive studies is inadequate. Coronary arteriography can help determine the severity and extent of coronary artery disease and is needed if revascularization is being contemplated. Endomyocardial biopsy can be used to identify the cause of cardiomyopathy. PMID- 8361945 TI - Are you recognizing depression in your patients? AB - Major depression is a prevalent condition that causes significant morbidity and mortality. Diagnosis may be complicated in depressed patients who offer a medical symptom as their chief complaint. Once the diagnosis is established, treatment is relatively straightforward. In prescribing an antidepressant, consideration should be given to the patient's previous response to medications, the documented efficacy of various agents, their side-effect profiles, and their potential for toxicity. Although the more severe and complicated cases should be referred to a psychiatrist, most depressed patients can be treated by their primary care physician. PMID- 8361946 TI - Modern management of epilepsy. Recommended medical and surgical options. AB - Effective treatment of epilepsy requires accurate diagnosis. This relies heavily on proper identification of seizure type, which may require long-term electroencephalography with video monitoring. Successful drug therapy requires a proper understanding of medication half-life and indications. Attempts should be made to control seizures with monotherapy; more than one agent should be tried only after monotherapy has failed. If medical management fails, surgical intervention should be considered. Such surgery is now considered relatively safe and highly effective. PMID- 8361947 TI - Increased striatal lipid peroxidation after intracerebroventricular MPP+ administration to mice. AB - Mice received different doses intracerebroventricularly of MPP+ (1-methyl-4 phenylpyridinium ion), the active metabolite of MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), a drug which induces a Parkinson model in rodents. Two indexes of lipid peroxidation were monitored at different times after administration: 1) production of thiobarbituric acid-reactive substances and 2) formation of lipid fluorescence products. A regional-selective overproduction of thiobarbituric acid-reactive substances was observed in corpus striatum and midbrain, but not in frontal cortex, cerebellum nor hippocampus. Enhancement was 70% and 198% at 30 and 60 min. in striatum and 88% at 30 min. in midbrain, when compared with respective controls injected intracerebroventricularly with saline solution. MPP+ also induced lipid fluorescence products formation enhancement in corpus striatum. This increase was dose-dependent in the range of MPP+ doses which induced striatal dopamine depletion. Striatal LFP formation was found increased 24 hr after MPP+ administration (38% vs control), indicating long lasting lipid peroxidation overproduction. These results suggest that lipid peroxidation might be involved in the neurotoxic effects of MPP+ in vivo. PMID- 8361948 TI - Increased biliary transferrin excretion following parenteral aluminium administration to rats. AB - Aluminium accumulates in the livers of patients receiving either parenteral nutrition or haemodialysis. When given parenterally to rats, aluminium causes cholestasis. However, the mechanism of hepatic aluminium uptake and the fate of aluminum in the liver are poorly understood. We examined the effect of parenteral aluminium administration on biliary excretion of transferrin, the major circulating aluminum-binding protein. Male Wistar rats were given parenterally aluminum 5 mg/kg/day for 1-14 days. Bile was collected for 3 hr at the end of the study period. Biliary total protein concentration and IgA/total protein were unaffected by up to 14 days of parenteral aluminium administration. However, biliary transferrin excretion increased with duration of aluminum administration up to five-fold by day 14. Biliary transferrin concentration and transferrin/total protein was higher in aluminum treated rats than controls after 7 and 14 days of study. Hepatic aluminum concentration reached a maximum after 4 days of parenteral aluminum administration, at which time serum bile acid and alanine amino transferase values were not different from controls. Since biliary transferrin is normally derived from the serum, it is likely that aluminum promotes hepatocellular uptake of transferrin and that aluminum enters the hepatocyte bound to transferrin. We postulate that transferrin may direct aluminum to intracellular sites where its toxic effects would be minimized. PMID- 8361949 TI - Bioactivation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine by liver microsomes from three different rat strains. AB - The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein binding of PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied using microsomes from PCB-pretreated or untreated male rats of the strains, Wistar, Fischer and Sprague-Dawley. The microsomal monooxygenases, P450IA1 and IA2, which are important for the biotransformation of heterocyclic amines, were quantified by immunoblots. The two metabolites detected, 2-amino-1 methyl-6-(4'-hydroxyphenyl)imidazo[4,5-b]pyridine (4'OH-PhIP) and 2-hydroxyamino 1-methyl-6-phenylimidazo[4,5-b]pyridine (N2-OH-PhIP) were formed in similar amounts whereas no minor metabolites were found in our highly sensitive radiochemical assay. Irrespective of the rat strain used, pretreatment with PCB significantly induced both the activation and the detoxication in all three rat strains. Except for a significantly higher concentration of P450IA2 in microsomes from control and PCB induced Wistar rats, no major differences between the strains were found. PMID- 8361950 TI - Potential antidepressive properties of amantadine, memantine and bifemelane. AB - The effects of amantadine, its dimethyl derivative, memantine and the chemically unrelated compound bifemelane were tested for antidepressant activity. Reserpine induced hypothermia and the forced swim test (Porsolt test) were selected for this purpose. In the former test amantadine and bifemelane but not memantine were effective. In the forced swim test all three agents produced antidepressive-like activity (decreased immobility time), but in case of bifemelane it was less pronounced. The effect in the forced swim test was specific i.e. it was apparently not the result of an increase in general activity as evidenced by control experiments in the open field. The mechanism of amantadine and memantine action may involve indirect dopaminomimetic activity resulting from the blockade of NMDA receptors. However in reserpine-induced hypothermia this explanation is not valid considering the lack of effect of memantine and positive action of amantadine. Hence, amantadine may have an additional central sympathomimetic action that memantine is lacking. Bifemelane antidepressant-like activity might be attributed to an enhancement of noradrenergic transmission. We suggested that amantadine and bifemelane could be particularly useful therapeutically when depressive symptoms are present in patients suffering from Parkinson's disease and dementia. PMID- 8361951 TI - Effects of 5-HT1A receptor agonists on patterns of rat motor activity in relation to effects on forebrain monoamine synthesis. AB - The effects of the 5-HT1A receptor agonists 8-OH-DPAT (0.15-2.5 mumol kg-1 subcutaneously), flesinoxan (0.6-10.0 mumol kg-1 subcutaneously) and buspirone (1.9-30.0 mumol kg-1 subcutaneously) on spontaneous motor activity in male Sprague-Dawley rats was examined in a photocell-equipped open-field arena. Following motor activity observations, the cerebral aromatic L-amino acid decarboxylase inhibitor NSD-1015 (100 mg kg-1 intraperitoneally) was administered and 30 min. later the animals were decapitated for subsequent analysis of the accumulated forebrain DOPA and 5-HTP levels, as an estimate of the rate of monoamine synthesis. 8-OH-DPAT and flesinoxan produced a similar and characteristic pattern of changes of the spontaneous motor activity in normal animals i.e. a moderate decrease in locomotor activity, a marked suppression of rearing and an increase in the relative amount of forward locomotion and of activity in the periphery of the open-field arena. This behavioural profile was closely related to a decrease in forebrain 5-HTP accumulation, indicating 5-HT receptor stimulation. In agreement with these observations buspirone also produced an increase in peripheral activity and a suppression of rearing. In contrast to effects by 8-OH-DPAT and flesinoxan, however, buspirone produced a further reduction of locomotor activity and reduced the forward locomotion. This difference in behavioural profile between buspirone and the other two compounds is probably explained by its DA receptor blocking properties, as indicated by an increased DOPA accumulation in the neostriatum. At least partially, 8-OH-DPAT, flesinoxan and buspirone, all antagonized reserpine-induced (5 mg kg-1 subcutaneously--16 hr) suppression of locomotor activity. This stimulation of locomotor activity in reserpine-treated rats is in all probability related to 5 HT1A receptor stimulation since concomitant DA D2 receptor blockade, in the case of buspirone, did not markedly affect this behavioural response. PMID- 8361952 TI - Purification and properties of malate dehydrogenase from Paracoccus denitrificans. AB - Affinity chromatography on immobilized Cibacron Blue (Matrex Gel Blue A) gel permeation chromatography on UltroPac TSK G 3000 SWG column and ion-exchange chromatography on "Mono Q" column were used to purify the malate dehydrogenase (MDH) from P. denitrificans to electrophoretic homogeneity. The last two purification steps were performed in FPLC system. The enzyme having a specific activity of about 2300 nkat/mg protein was obtained with an approximate 70% yield. MDH is a dimer with a molecular mass of 80,000 +/- 10,000 and an isoelectric point of 4.85 +/- 0.05. Absorption, fluorescence and CD-spectra were also measured and basic kinetic parameters were obtained for the homogeneous enzyme. The present paper also suggests the possibility of using the prepared enzyme for the determination of aspartate transferase (AST) in blood serum. PMID- 8361953 TI - Improved chromatographic purification of pea seedlings diamine oxidase. AB - An improved and simplified purification procedure has been developed for the isolation of diamine oxidase from pea seedlings (DAO EC 1.4.3.6). It involves ammonium sulphate precipitation, hydrophobic interaction chromatography, ion exchange chromatography and size-exclusion chromatography. The homogeneity of the final enzyme preparations and molecular weight were determined by size-exclusion chromatography and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (SDS PAGE). The isoelectric point of 7.35 +/- 0.05 was determined by chromatofocusing and by polyacrylamide gel isoelectric focusing. PMID- 8361954 TI - Purification of a second kallikrein from bovine pancreas. AB - Two kallikreins were identified in a homogenate of bovine pancreas in terms of their differential elution from an anion-exchange chromatography column. The kallikreins were quantified by their ability to release kinin from a partially purified preparation of bovine kininogen. The second kallikrein, designated kallikrein B, was purified by a three-step procedure following anion-exchange chromatography consisting of affinity chromatography on a benzamidine-agarose resin, gel filtration and hydrophobic interaction chromatography. An overall purification factor of 556-fold was achieved with a 58% recovery of enzymatic activity. The final material was shown to be homogeneous by a number of electrophoretic analyses. The relative molecular mass of pro-kallikrein B was found to be 26,700 by gel filtration and that of kallikrein B to be 26,000 by SDS gel electrophoresis. Gel isoelectric focusing revealed the presence of several isoenzymic forms ranging in isoelectric point from pH 4.05 to 4.35. PMID- 8361955 TI - Study on the purification of growth hormone-like substance from pituitaries of the snake Ptyas mucosa. AB - Extract from the snake (Ptyas mucosa) pituitaries was capable of inhibiting the binding of 125I-labelled bovine growth hormone to female rat liver membranes. The growth hormone-like substance was not adsorbed on Concanavalin A-Sepharose nor DEAE-cellulose, but could be purified by gel filtration on Sephadex G-50. It possessed a molecular weight of about 19,000 as judged by SDS-polyacrylamide gel electrophoresis. The iodinated snake growth hormone-like substance bound to membranes prepared from female rat and pregnant rabbit livers. The binding could be inhibited by unlabelled snake growth hormone-like substance as well as by bovine growth hormone. PMID- 8361956 TI - Characterization of human kappa-casein purified by FPLC. AB - Because previous purification procedures for human kappa-casein may have caused the loss of some carbohydrate, relatively gentle methods were used. The protein was isolated by a four-step procedure which included isoelectric precipitation of whole casein, gel chromatography on Sephadex G-200 in the presence of SDS, removal of the SDS with Extracti-Gel D, and FPLC chromatography on Mono Q with buffers containing 6 M urea. The purified protein was nearly identical in amino acid composition to that found earlier by amino acid analysis and peptide sequencing and a molar extinction coefficient of 11.2 +/- 0.1 was determined on the basis of amino acid analysis with a norleucine internal standard. Hydrolysis, acylation, and methylsilylation of the carbohydrate, followed by gas chromatographic analysis on a fused silica column, yielded approximately 5% fucose, 17% galactose, 18% N-acetylglucosamine, 8% N-acetylgalactosamine and 7% sialic acid, totaling almost 55% by weight. The percentages from two different donors were almost the same. About 1 mole phosphorus per mole of kappa-casein was also detected. Using low-speed sedimentation equilibrium methods, a molecular weight of only 33,400 was obtained for human kappa-casein, suggesting carbohydrate lability. Human beta-casein with four phosphoryls was stabilized against precipitation by 10 mM Ca+2 ions at a level greater than 95% when the molar ratio of kappa/beta exceeded 0.15. PMID- 8361957 TI - Selective extraction of alkaline phosphatase and 5'-nucleotidase from milk fat globule membranes by a single phase n-butanol procedure. AB - A single phase extraction procedure employing 8% (v/v) n-butanol at room temperature extracted over 90% of alkaline phosphatase activity and over 60% of 5'-nucleotidase activity from bovine milk fat globule membranes (MFGM). For 5' nucleotidase, higher n-butanol concentrations lead to loss of activity, while lower concentrations were ineffective in extracting the enzyme. When extractions were performed at 0 degrees C, similar yields were obtained for alkaline phosphatase extraction with 8% (v/v) n-butanol, but 5'-nucleotidase extraction required 10% (v/v) n-butanol for similar yields. However, 5'-nucleotidase was less susceptible to denaturation during extraction at 0 degrees C. The Km values and substrate specificities for both alkaline phosphatase and 5'-nucleotidase were unchanged by extraction with 8% (v/v) n-butanol. The 8% (v/v) n-butanol extraction procedure provides a 3-fold purification step, and an enzyme preparation suitable for further purification. PMID- 8361959 TI - Enhanced sensitivity of pancreatic cells to cholecystokinin octapeptide in obstructive jaundice. AB - Exocrine function of the pancreas in obstructive jaundice was examined using dogs. Jaundice induced by choledochal ligation over 3 weeks showed pancreatic hypersecretion in response to cholecystokinin octapeptide (CCK-8) stimulation. To clarify the mechanism of pancreatic hypersecretion in obstructive jaundice, three experiments were undertaken. In a perfusion experiment performed on isolated pancreas, hypersecretion in obstructive jaundice was observed in response to CCK 8 stimulation. An incubation experiment showed an increase in secretion in response to CCK-8 stimulation in a dose-dependent manner, producing a greater increase in dogs with obstructive jaundice than in controls, despite the fact that basal secretion in both groups was the same. This would suggest that at least one of the mechanisms of pancreatic hypersecretion in obstructive jaundice may be related to the degree of sensitivity of acinar cells to CCK-8. In morphological observation of acinar cells by electron microscopy, the average number of zymogen granules and total granular area per unit of cytoplasm in both groups before and after stimulation with CCK-8 were compared. There was no difference between the groups before stimulation. Following stimulation, values for the control group decreased but appeared to increase in the jaundiced pancreas. These results strongly suggest that pancreatic acinar cells in obstructive jaundice may retain their secretory potential after stimulation for 60 min, though the potential in nonjaundiced pancreatic acinar cells may decrease after stimulation. PMID- 8361958 TI - Neurons containing gastrin releasing peptide-like immunoreactivity in the human pancreas. AB - Gastrin releasing peptide (GRP) is known to stimulate pancreatic enzyme and islet hormone secretion. In the present immunohistochemical study, the localization and distribution of GRP-like immunoreactivity were investigated in the human pancreas using two antisera with different specificities. GRP-like immunoreactivity (GRP LI) was observed in numerous nerve fibers diffusely distributed to the exocrine pancreas, but was not seen in intrapancreatic nerve cells of normal pancreatic specimens examined. Nerve fibers and terminals with GRP-LI were found in abundance around pancreatic acini and capillaries, with moderate density around ductules and in the walls of arterioles, and a few were seen in islets. This distribution pattern was quite similar to that of vasoactive intestinal polypeptide (VIP)-LI nerve fibers. The study, using the antibody elution method, strongly suggests the co-localization of GRP- and VIP-LIs within a part of VIP containing nerve fibers. In the chronic pancreatitis specimens, neurons with GRP LI were frequently found, and > 90% of intrapancreatic nerve cells were VIP immunoreactive. Immunostainings for GRP and for VIP on serial adjacent sections of intrapancreatic ganglia from chronic pancreatitis specimens suggested the co localization of the two immunoreactivities in > 70% of intrapancreatic neurons. The present findings may provide a morphological basis for neurotransmitter and/or neuromodulator roles of GRP in the human pancreas. PMID- 8361960 TI - Does acetylsalicylic acid interfere with stimulated pancreatic secretion? An experimental study in the rat. AB - To evaluate the effect of the prostaglandin inhibitor acetylsalicylic acid (ASA) on rat exocrine pancreas secretion, three groups of rats were administered ASA by infusion: Groups 1-3, 50, 100, and 200 mg/kg body wt, respectively; Group 4 received saline. Twenty minutes later these ASA-pretreated groups were given intraarterial secretin (18 CU/kg) and cholecystokinin (CCK) (18 micrograms/kg). In an additional three groups of seven rats each, saline solution rather than secretin-CCK was given after ASA pretreatment. Pancreatic juice was collected every 10 min by means of a chronic pancreatic fistula. Bicarbonate and protein concentrations were measured and variations in outputs observed. No significant variations were found in the bicarbonate concentrations and outputs of rats with different types of pharmacological treatment, while protein concentrations and outputs were found to vary with time and type of experiment. There was, however, no interaction between these two variables. At lower ASA dosages, the bicarbonate and protein concentrations and outputs of secretin-CCK-stimulated rats were higher than the basal values and the levels of rats without hormonal stimulation. At higher dosages, no difference was found between the two groups. In conclusion, ASA seems to interfere with stimulated pancreatic exocrine secretion of proteins, even when its effect on bicarbonate concentration is factored in, and its effect seems to be present at the highest dosages considered in the study. Among the various hypotheses that may explain this phenomenon, an antagonizing effect of ASA on secretin-CCK action should be the first to be considered. PMID- 8361961 TI - Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum. AB - Following ingestion of a meal, unabsorbed nutrients may reach the distal intestine partly after the termination of the prandial period, i.e., in the presence of interdigestive motor and secretory patterns. To determine if interdigestive motility and pancreatic enzyme secretion are modulated by the delivery of nutrient into the ileal lumen, six fasting volunteers were intubated with an oroileal multilumen tube system that permitted multiple small intestinal manometry, gastric and duodenal aspiration, and perfusions of marker and test solutions. Ileal perfusions of nutrient or saline solutions were started during phase I of the interdigestive motility cycle. Ileal perfusion with carbohydrate or lipids increased the duration of motor quiescence and decreased the length of the interdigestive cycle, mainly by decreasing the proportion of phase II activity compared with ileal saline (p < 0.01). Pancreatic outputs of amylase, trypsin, and chymotrypsin prior to ileal perfusions were low because, due to the protocol, perfusions were started during phase I. With ileal saline, enzyme outputs increased (p < 0.05) in association with the occurrence of phase II motility, as expected. By contrast, ileal carbohydrate and triglyceride perfusion prevented the phase II-associated increase in enzyme outputs (p < 0.05). The data suggest that the presence of nutrients within the ileal lumen may modulate interdigestive motor and pancreatic functions. PMID- 8361962 TI - Putrescine uptake in rat pancreatic acini: effect of secretagogues and growth factors. AB - Polyamines [putrescine (Put), spermidine, and spermine] are normal cellular constituents that can modulate cellular proliferation and differentiation in a number of tissue and cell types. Transport is one of the mechanisms that control intracellular polyamine content. The present investigation explores the influence of cholecystokinin (CCK), other secretagogues [carbachol, bombesin, vasoactive intestinal polypeptide (VIP)], insulin, insulin-like growth factor 1 (IGF-1), and epidermal growth factor (EGF) on Put uptake in rat pancreatic acini. Insulin, IGF 1, and EGF stimulated Put uptake by 30-40%. Insulin did not enhance intracellular metabolism of Put. In contrast, CCK and the other secretagogues inhibited this transport system by 40-50% of control (VIP by 23% only). Further investigations of the inhibitory effect of CCK revealed that the maximal uptake rate of Put (Vmax) shifted from 346 pmol [14C]Put/mg DNA-min (control) to 265 pmol [14C]Put/mg DNA-min (100 pM CCK), whereas the Km was only moderately influenced. Augmented Put efflux as well as increased production of endogenous Put (possibly induced by CCK) did not contribute to this change in transport kinetics. In addition, the inhibition of Put uptake induced by CCK was specific and dose dependent up to 100 pM. CCK at 1,000 pM exerted only minor inhibition (20% of control). Incubation with the Ca-ionophore A 23187 did not influence Put accumulation, whereas treatment with the phorbol ester phorbol 12-myristate-13 acetate led to enhanced Put uptake (30-40%). Pretreatment of the acini with 1 mM ouabain led to a reduction of Put uptake by 43%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361963 TI - Release of platelet-activating factor in acute experimental pancreatitis. AB - This study demonstrates the formation of platelet-activating factor (PAF) in rats with acute experimental pancreatitis (AEP). The AEP was induced by infusing sodium taurodeoxycholate and trypsin into the bile-pancreatic duct. The PAF content was increased in blood samples and in pulmonary and pancreatic tissue as compared with control animals. Significant amounts of PAF were also found in peritoneal fluid. The PAF content did increase in blood samples and in pulmonary tissue after administration of endotoxin intravenously. The effects of intraperitoneal PAF administration were also studied and showed an increase of polymorphonuclear cells in blood samples. These findings suggest that acute pancreatitis might generate and release PAF. Whether PAF release is associated with the pathophysiology of complications in acute pancreatitis remains to be elucidated. PMID- 8361964 TI - Ethionine-induced atrophy of rat pancreas involves apoptosis of acinar cells. AB - The mechanism of acinar cell loss occurring during ethionine-induced atrophy of the pancreas was investigated. Rats were given a standard diet, a protein depletion diet (PDD), or a PDD with low- (0.04 g/kg body wt; LDE) or high- (0.4 g/kg; HDE) dose ethionine administered intraperitoneally daily for 10 days. Changes were most extensive in the animals given a PDD and HDE: After 10 days, pancreatic weight was reduced by 72%, and most of the acinar cells had disappeared. Prior to their deletion, these cells showed cytoplasmic vacuolation and enhanced autophagy. The main mechanism involved in their deletion was apoptosis, the apoptotic bodies being phagocytosed and degraded by adjacent acinar cells and intraepithelial macrophages. In contrast, necrosis of acinar cells was rare. Interstitial inflammation and apoptosis of capillary endothelial cells were also observed. In animals given a PDD and LDE, enhanced apoptosis occurred later and was more limited in extent, and additional manifestations of cell injury were not evident. As in other circumstances where glandular atrophy is effected by apoptosis, the basic tissue architecture was preserved, thus explaining the known capacity for the pancreas to regenerate after ethionine is discontinued. PMID- 8361965 TI - The effect of epinephrine on insulin and glucagon secretion from the endotoxic rat pancreas. AB - This study determined whether in vivo endotoxin treatment alters the ability of epinephrine to inhibit immunoreactive insulin (IRI) secretion or to stimulate immunoreactive glucagon (IRG) secretion from the in vitro perfused rat pancreas preparation. Insulin and glucagon secretion were measured from pancreases obtained from control and endotoxin-treated rats. The pancreases were perfused with 240 mg/dl glucose in the presence and the absence of 13.6 nM epinephrine. The absolute ability of epinephrine to inhibit glucose-induced IRI secretion was similar for both "control" and "endotoxic" pancreases. However, since endotoxic pancreases hypersecrete insulin, the relative ability of epinephrine to inhibit insulin secretion was reduced in endotoxic compared with control pancreases. Epinephrine did not appreciably alter IRG secretion in control pancreases. However, epinephrine prevented a progressive decrease in IRG secretion in endotoxic pancreases. The results suggest that the relative inability of epinephrine to inhibit the excess insulin secretion due to endotoxin treatment contributes to endotoxin-induced hyperinsulinemia. Furthermore, the additional observation that epinephrine supported glucagon secretion in the endotoxic pancreas in the face of high glucose levels suggests epinephrine may play a deleterious role with respect to glucose homeostasis during endotoxicosis. The results provide a partial mechanism to explain endotoxin-induced hyperinsulinemia and also demonstrate a possible role for epinephrine with regard to the production of elevated glucagon levels during endotoxicosis. PMID- 8361966 TI - Extraislet infiltration in NOD mouse pancreas: observations after immunomodulation. AB - This study describes the morphology, time appearance, persistence, and immunomodulation of extraislet infiltration in the nonobese diabetic (NOD) mouse pancreas. Female NOD mice were subdivided into two groups: untreated, killed at week 5 (n = 8), 10 (n = 8), or 21 (n = 8) of life; ganglioside treated (200 mg/kg body wt/day given from week 4 until week 21 of life, plus complete Freund's adjuvant at week 4), killed at week 10 (n = 6), 21 (n = 6), or 25 (4 weeks after the end of the ganglioside treatment; n = 6). Mononuclear elements were seen around small ductules located both in the vicinity of and far from the islets. Larger ducts were completely devoid of inflammation, thus evidencing that periductulitis is specific only to small ductules. Moreover, an exocrine focal pancreatitis was seen along septa and may demonstrate that macrophage activation takes place throughout the pancreatic connective tissue. Immunomodulation determines some suppression of insulitis; nevertheless, after treatment withdrawal, a reinfiltration occurs both within and outside the islets. PMID- 8361967 TI - Xanthine oxidase-mediated intracellular oxidative stress in response to cerulein in rat pancreatic acinar cells. AB - Intralobular oxygen radical formation was examined in cerulein-stimulated rat pancreatic acinar cells by digital imaging microscopic fluorography using a hydroperoxide-sensitive fluorescent probe, dichlorofluorescin (DCFH) diacetate. The isolated pancreatic acinar cells loaded with DCFH diacetate were microscopically observed, and the dichlorofluorescein (DCF) fluorescence yielded by DCFH oxidation via hydroperoxides was digitally processed. Within the initial 20 min after the application of cerulein (10 microM), intracellular oxidative stress was observed as indicated by the increase in DCF fluorescence intensity and reached its maximum at 60 min. DCF fluorescence intensity was then gradually decreased until 80 min, followed by a marked increase in propidium iodide (PI) fluorescence, suggesting irreversible cell death. Allopurinol (1 microM), a xanthine oxidase inhibitor, significantly attenuated the early increase of DCF fluorescence intensity as well as the late cell damage. Treatment with hyperbaric oxygen (PO2 300 mm Hg) also significantly attenuated both the increase of DCF fluorescence and the number of PI-positive cells. The results suggest that xanthine oxidase-mediated oxygen radicals may play an important role in cerulein induced intracellular oxidative stress in pancreatic acinar cells of rats. PMID- 8361968 TI - Inhibitory effect of intraduodenal administration of somatostatin analogue SDZ CO 611 on rat pancreatic exocrine secretion. AB - The inhibitory effect of the intraduodenal administration of a new somatostatin analogue, SDZ CO 611 (SDZ), on pancreatic secretion was evaluated in the rat. The exocrine pancreas was stimulated by either intravenous infusion of both secretion (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 microgram/kg/h) or intraduodenal infusion of oleic acid (0.25 mmol/h) or casein (200 mg/h). Intraduodenal administration of SDZ in three different doses, 0.5, 1.0, and 2.0 mg/kg/h, resulted in dose-related inhibition of pancreatic secretion, including juice volume, bicarbonate, and amylase, stimulated by exogenous secretin and CCK. Intraduodenal oleic acid- and casein-induced increases in pancreatic secretion in terms of juice volume, bicarbonate, and amylase were also significantly suppressed by intraduodenal administration of SDZ in a dose of 2.0 mg/kg/h. Moreover, SDZ (2.0 mg/kg/h) significantly inhibited basal pancreatic secretion. It is concluded that the intraduodenal administration of SDZ inhibits pancreatic secretion stimulated by exogenous secretin and CCK-8 in physiological doses and by intestinal nutrients in the rat. PMID- 8361969 TI - Identification of enterostatin, the pancreatic procolipase activation peptide in the intestine of rat: effect of CCK-8 and high-fat feeding. AB - Enterostatin, the procolipase activation peptide, has been suggested in previous studies to act as a satiety signal for food intake, with a specificity for fat intake. In this study, by use of a competitive enzyme-linked immunosorbent assay with a detection limit of 4.115 nmol/L and within 6% intra- and interassay variation, the immunoreactive and chromatographic characterization of enterostatin in intestinal content was undertaken in Sprague-Dawley rats. Following intravenous infusion of cholecystokinin octapeptide (CCK-8; 200 pmol/kg/h) for 60 min, the concentration of intestinal enterostatin increased from a basal level of 2.0 +/- 0.7 microM to 5.64 +/- 1.1 microM at time point 60 min. The enterostatin level remained at 4.24 +/- 0.54 microM for 120 min after the CCK infusion had ceased. Pancreatic lipase and colipase activities in rat intestinal content also increased during the CCK-8 infusion. The enzyme activities reached the maximal level after 30 min of CCK infusion and thereafter progressively decreased to basal levels, remaining there during the following 2 h. The basal level of intestinal enterostatin in rats fed with standard pellets was found to be increased from 1.42 +/- 0.14 to 3.86 +/- 0.4, 3.17 +/- 0.54, and 5.02 +/- 1.6 microM on days 1, 3, and 7, respectively, after high-fat feeding. Parallel to the increase in intestinal enterostatin, there was a significant increase in pancreatic lipase and colipase activities in the intestine during the ingestion period of high-fat diet as compared with the control group. The estimated molecular mass of enterostatin immunoreactivity of intestinal content was similar to that of the synthetic pentapeptide. These results suggest that immunoreactive enterostatin (Val-Pro-Gly-Pro-Arg) is normally present in rat intestinal content, is significantly increased after stimulation with CCK-8, and is also increased after prolonged high-fat feeding. PMID- 8361970 TI - Pancreatic cancer presenting with resolving pseudocyst during octreotide therapy. AB - Pancreatic cancer presenting as acute pancreatitis is relatively uncommon. Pancreatic cancer should be included in the differential diagnosis of "idiopathic" acute pancreatitis, particularly in the elderly. The following case report describes a patient in whom pancreatic cancer presented as acute pancreatitis with pseudocyst formation and subsequent resolution with octreotide therapy. Various implications of this case are reviewed. PMID- 8361971 TI - Methods to facilitate early exploratory testing of novel psychopharmacologic agents in humans. PMID- 8361972 TI - Diagnostic heterogeneity in relation to drug evaluation: antidepressants. PMID- 8361973 TI - Serotonin receptor subtypes. PMID- 8361974 TI - Dose-effect relationships for tricyclic antidepressants: the basis for rational clinical testing of new antidepressants. PMID- 8361975 TI - Dose-effect and concentration-effect relationships with new antidepressants. PMID- 8361976 TI - Therapeutic potentials of recently introduced antidepressants. Danish University Antidepressant Group. AB - The DUAG studies showed that in well-designed and rigorously executed multisite drug trials three representatives (citalopram, paroxetine, and moclobemide) from two classes of recent antidepressant drugs were less effective than the standard reference drug, clomipramine. The most important reasons for the superiority of clomipramine was probably that clomipramine was given in a high and fixed dose of 150 mg per day throughout the entire treatment period and that patient compliance was ensured through drug monitoring. When the DUAG studies are compared with "no difference" studies, the difference between DUAG and others lies not so much in a different efficacy of the test drugs but in the efficacy of the reference drugs, where clomipramine in the DUAG studies was more effective than reference tricyclics in most other studies with flexible dose regimens. A relatively high rate of adverse drug reactions with clomipramine administered in high and fixed doses was probably due to a considerable interindividual variability in the pharmacokinetic properties. (Gram 1990), and the development of side effects may be predicted and prevented when better knowledge of plasma concentration and dose response relations for classical tricyclic antidepressants allow individual dose adjustments. Such studies are under way with in the DUAG. The results of such studies may reduce the need for new antidepressants which, although less toxic than the classical tricyclics, may prove to be also less potent. The DUAG studies were performed in hospitalized, moderately to severely, endogeneously depressed adult patients and conclusions from the DUAG studies about the superiority of clomipramine over three recent antidepressants cannot readily be generalized to cover less homogeneous groups of outpatients with milder depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361977 TI - Role of genetic polymorphism in psychopharmacology--an update. PMID- 8361978 TI - Phenotypes for psychotropic drug metabolism in the elderly. PMID- 8361979 TI - Analysis of 935 haloperidol concentration measurements obtained during routine drug monitoring of 134 patients. PMID- 8361980 TI - Developmental regulation of 5-HT2 and 5-HT1c receptor gene expression in rat brain. PMID- 8361981 TI - Relevance of 5-HT autoreceptors for psychotropic drug action. PMID- 8361983 TI - Monthly prostaglandin bibliography prepared by Sheffield University Biomedical Information Service. PMID- 8361982 TI - Brain serotonin subsystem complexity and receptor heterogeneity: therapeutic potential of selective serotonin agonists and antagonists. PMID- 8361984 TI - The lupus anticoagulant and eicosanoids. PMID- 8361985 TI - Effect of chronic ethanol consumption on the spontaneous contractions, prostaglandin production, triglycerides and glucose metabolism of uterine strips isolated from pregnant rats and in embryos. AB - The constancy of spontaneous isometric developed tension (IDT) and the metabolism of triglycerides (TGs), U-14C-Glucose and 14C-arachidonic acid (14C-AA) in uterine strips isolated from controls and from chronic ethanol (ETOH) fed pregnant rats were explored. The studies were performed on isolated uterine strips suspended in glucose-containing as well as a glucose-free medium. The spontaneous decrement of IDT as time progressed after tissue isolation and mounting was significantly higher in tissue preparations obtained from pregnant rats drinking 20% ETOH, than the controls. This situation was evident in uterine strips isolated from rats at 10 and at 16 days of pregnancy, both in solutions containing glucose or in glucose-free conditions. On the other hand, uterine strips isolated from control rats at 7, 10 and 16 days of pregnancy exhibited almost no decrement of IDT after 60 min of activity in a solution containing glucose or in a glucose-free medium. The absolute values of TGs in uteri obtained from rats drinking ETOH were significantly greater (p < 0.001) than in non drinking controls. TG levels did not differ at 0 min (initial or postisolation) to those at 60 min in control uterine preparations obtained from pregnant rats at 7, 10 or 16 days of pregnancy and incubated either in a medium with or without glucose. On the contrary, in strips from ETOH-fed animals isolated on the same day of pregnancy, TG levels determined at 60 min following isolation and mounting were significantly lower, when glucose was present or absent from the suspending solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361986 TI - Tiaprofenic acid inhibits the renal reabsorption of sulfate in rats. AB - The objectives of the current investigation were: (1) to examine the effects of the nonsteroidal anti-inflammatory drug, tiaprofenic acid (TA), on sulfate renal reabsorption, and (2) to determine if concomitant prostaglandin E2 (PGE2) could reverse these effects. In crossover studies, female Lewis rats (n = 9) received either TA (as an intravenous (i.v.) bolus injection of 15 mg/kg and constant infusion of 0.02 mg/min) or its vehicle for 6 h. A blood sample was obtained at 5 h and urine was collected between 4 and 6 h. At a steady-state TA serum concentration of approximately 190 micrograms/ml, the PGE2 urinary excretion rate was inhibited by > 90% with no change in glomerular filtration rate (GFR), as measured by creatinine clearance. TA administration resulted in a significant decrease in serum sulfate concentrations (0.65 +/- 0.22 vs 1.1 +/- 0.15 mM, mean +/- SD, p < 0.01) and increase in sulfate clearance ratio (0.32 +/- 0.14 vs 0.13 +/- 0.06, p < 0.01) when compared to the vehicle-treated period. There was also a significant decrease in the fraction of sulfate reabsorbed by the kidneys (0.68 +/- 0.14 vs 0.87 +/- 0.06 in the vehicle-treated period, p < 0.01). In a second crossover study, rats received either TA or TA plus PGE2. PGE2 was administered as an infusion (0.1 micrograms/min) beginning 210 min after the start of the TA infusion. An additional group of rats served as controls and received both vehicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361987 TI - The effect of regular and enteric-coated aspirin on bleeding time, thromboxane, and prostacyclin. AB - We compared the effect of different aspirin schedules, dosages, and formulations on various bleeding time parameters including bleeding time, plasma and total blood volume, and levels of the stable metabolites of thromboxane A2 (TXA2) and prostacyclin (PGI2) (respectively, TXB2 and 6-keto-prostaglandin F1 alpha (6-keto PGF1 alpha)) to determine the optimal dosage and formulation of aspirin to inhibit TXA2 production while sparing PGI2. In a randomized, parallel study, 52 healthy male volunteers (62 independent observations) with no history of bleeding disorders were given 80 mg or 325 mg of regular aspirin, or 325 mg of enteric coated aspirin to ingest daily (14 pills) or every other day (7 pills) for a continuous 14 day period. Bleeding times were performed on day 1 before aspirin, 6 h after aspirin on day 1, and before aspirin on day 14. Bleeding times, plasma volume, and total volume increased significantly from before aspirin to after 6 h and 14 days (p < 0.0001 for all parameters) for all aspirin formulations. For day 1 before aspirin ingestion to 6 h later, both TX and PGI2 (p < 0.008) decreased significantly. 6 h after ingestion of aspirin on day 1 to day 14, both TX and PGI2 levels also significantly decreased (p < 0.0001). There was a highly significant decrease in PGI2 production on every other day aspirin schedules (p = 0.0001) particularly with 80 mg of aspirin, while the decrease in PGI2 production on daily aspirin was not significant (p = 0.10). The most favourable ratio of 6 keto-PGF1 alpha to TXB2 occurred with 80 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8361988 TI - Increased thromboxane A2 production at primary tumor site in metastasizing squamous cell carcinoma of the larynx. AB - In order to evaluate the possible role of prostaglandins (PG) in invasion and metastasis of malignant cells in larynx carcinoma, arachidonic acid (AA) metabolite production by tumor tissue, peritumor tissue and node metastasis was investigated in comparison to that by healthy mucosa and unaffected lymph nodes. The study was performed by evaluating PGE2, 6ketoPGF1 alpha and thromboxane B2 (TXB2) production by radioimmunoassay in specimens from eight patients who underwent surgical treatment. The highest rate of AA metabolism was observed in peritumor tissue. PGE2 was the main metabolite produced in all tissues and its levels were significantly higher than those of 6ketoPGF1 alpha and TXB2 (p < 0.05). 6ketoPGF1 alpha production was higher (p < 0.01) than that of TXB2 and did not significantly change among the different tissues. TXB2 production was significantly increased (p < 0.05) by peritumor tissue as compared to healthy mucosa. The ratio between TXB2 and 6ketoPGF1 alpha production was found to be almost twofold higher in tumor tissue, peritumor tissue, metastatic and non metastatic lymph nodes as compared to control tissue. The lowest AA metabolism was found in affected lymph nodes. These findings demonstrate a different AA metabolism at primary tumor sites in comparison to healthy mucosa suggesting a prometastatic role of TXB2 and supporting the hypothesis of the occurrence of an imbalance between TXB2 and 6ketoPGF1 alpha production in favouring metastatic spread. PMID- 8361989 TI - Interaction between vitamin B6 deficiency and low EFA dietary intake on kidney phospholipids and PGE2 in the rat. AB - Vitamin B6 is involved in the metabolism of long chain polyunsaturated fatty acids and phospholipids. We have studied the interaction between pyridoxine deficiency and low amounts of dietary essential fatty acids (EFA) in the rat. The fatty acid composition of kidney phospholipids of pyridoxine deficient animals shows a decrease of 20:3 n9 and an increase of 20:4 n6 in comparison with control and pair fed animals. This variation of fatty acid composition could be due to the simultaneous effect of vitamin B6 deficiency, which reduces the oxidation of linolenate, and of a low intake of EFAs which stimulates delta-6-desaturase. The dietary treatment also influences kidney Prostaglandin E2 (PGE2) levels which are higher in vitamin B6 deficient animals. This effect could be correlated with a higher response to sympathetic stimulation caused by the simultaneous presence of vitamin B6 deficiency and low EFA availability. Also the higher level of arachidonate could be involved in promoting PGE2 synthesis. PMID- 8361990 TI - Metabolic polymorphisms. AB - Polymorphisms have been detected in a variety of xenobiotic-metabolizing enzymes at both the phenotypic and genotypic level. In the case of four enzymes, the cytochrome P450 CYP2D6, glutathione S-transferase mu, N-acetyltransferase 2 and serum cholinesterase, the majority of mutations which give rise to a defective phenotype have now been identified. Another group of enzymes show definite polymorphism at the phenotypic level but the exact genetic mechanisms responsible are not yet clear. These enzymes include the cytochromes P450 CYP1A1, CYP1A2 and a CYP2C form which metabolizes mephenytoin, a flavin-linked monooxygenase (fish odour syndrome), paraoxonase, UDP-glucuronosyltransferase (Gilbert's syndrome) and thiopurine S-methyltransferase. In the case of a further group of enzymes, there is some evidence for polymorphism at either the phenotypic or genotypic level but this has not been unambiguously demonstrated. Examples of this class include the cytochrome P450 enzymes CYP2A6, CYP2E1, CYP2C9 and CYP3A4, xanthine oxidase, an S-oxidase which metabolizes carbocysteine, epoxide hydrolase, two forms of sulphotransferase and several methyltransferases. The nature of all these polymorphisms and possible polymorphisms is discussed in detail, with particular reference to the effects of this variation on drug metabolism and susceptibility to chemically-induced diseases. PMID- 8361991 TI - The role of phosphodiesterase inhibitors in heart failure. AB - Myocardial contractility is dependent on available intracellular calcium and this can be enhanced by increasing intracellular cyclic adenosine monophosphate. One way of achieving this is by inhibiting the phosphodiesterase III enzyme. Over the last 15 years, a number of new drugs with this mechanism of action have been studied in man and have been found not only to have a positive inotropic action on the heart but also a vasodilating action on peripheral blood vessels. This combination of effects produces favourable haemodynamic improvement in patients with chronic heart failure. While some smaller studies showed that this did translate into an improvement in symptoms and functional capacity, a large well designed and controlled clinical trial showed that survival was decreased when milrinone was used in target daily doses of 40 mg. For this reason, chronic long term oral therapy with phosphodiesterase III inhibitors is not currently being actively pursued. They may still have a role as acute short-term therapy in severely ill patients who do not respond adequately to optimal standard drug therapy. Milrinone has been one of the most widely studied drugs in this regard. Even during short-term administration, its use should be closely monitored for any evidence of an increase in ventricular arrhythmias or decrease in ventricular function. PMID- 8361992 TI - Neuronal control of airways smooth muscle. AB - Sensory afferent nerves relay impulses from the airways to the central nervous system so that appropriate changes in bronchomotor tone and breathing patterns may occur. The dominant efferent control of airways smooth muscle is exerted via bronchoconstrictor parasympathetic cholinergic nerves. In some species this is opposed by bronchodilator sympathetic noradrenergic nerves. In addition, there exist both excitatory bronchoconstrictor and inhibitory bronchodilator non adrenergic, non-cholinergic pathways. This review examines the role of the different branches of the autonomic nervous system in the control of airways smooth muscle tone with particular reference to modulation of these branches and the interactions which may exist between them. PMID- 8361993 TI - Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum. AB - Quinoline-containing drugs such as chloroquine and quinine have had a long and successful history in antimalarial chemotherapy. Although these drugs are known to accumulate by a weak base mechanism in the acidic food vacuoles of intraerythrocytic trophozoites and thereby prevent hemoglobin degradation from occurring in that organelle, the mechanism by which their selective toxicity for lysosomes of malaria trophozoites is achieved has been subject to much discussion and argument. In this review the recent discovery that chloroquine and related quinolines inhibit the novel heme polymerase enzyme that is also present in the trophozoite food vacuole is introduced. The proposal that this inhibition of heme polymerase can explain the specific toxicity of these drugs for the intraerythrocytic malaria parasite is then developed by showing that it is consistent with much of the disparate information currently available. The clinical usefulness of chloroquine, and in some recent cases of quinine as well, has been much reduced by the evolution and spread of chloroquine resistant malaria parasites. The mechanism of resistance involves a reduced accumulation of the drug, although again the mechanism involved is controversial. Possible explanations include an energy-dependent efflux of preaccumulated drug via an unidentified transmembrane protein pump, or an increase in vacuolar pH such that the proton gradient responsible for drug concentration is reduced. New data are also presented which show that heme polymerase isolated from chloroquine resistant trophozoites retains full sensitivity to drug inhibition, consistent with the observation that resistance involves a reduced accumulation of the drug at the (still vulnerable) target site. The significance of this result is discussed in relation to developing new strategies to overcome the problem presented by chloroquine resistant malaria parasites. PMID- 8361994 TI - P450 enzymes of estrogen metabolism. AB - Endogenous and exogenous estrogens undergo extensive oxidative metabolism by specific cytochrome P450 enzymes. Certain drugs and xenobiotics have been found to be potent inducers of estrogen hydroxylating enzymes with C-2 hydroxylase induction being greater than that of C-16 hydroxylase. Oxygenated estrogen metabolites have different biological activities, with C-2 metabolites having limited or no activity and C-4 and C-16 metabolites having similar potency to estradiol. Pathophysiological roles for some of the oxygenated estrogen metabolites have been proposed, e.g. 16 alpha-hydroxyestrone and 4 hydroxyestrone. These reactive estrogens are capable of damaging cellular proteins and DNA and may be carcinogenic in specific cells. PMID- 8361996 TI - Cyclosporin metabolism in transplant patients. AB - The immunosuppressant cyclosporin, a cyclic undecapeptide, is metabolized to more than 30 metabolites. Cytochrome P450IIIA enzymes located in liver and small intestine are responsible for the biotransformation of cyclosporin and its metabolites and are the site of several drug interactions. It is still under discussion, whether the cyclosporin metabolites are involved in the immunosuppressive and/or toxic activities of cyclosporin. While isolated metabolites show not more than 10-20% of the activity of the mother compound in vitro, metabolite combinations have additive and synergistic effects. Isolated metabolites show no toxic effects in rat models while there is an association between metabolite blood concentrations and cyclosporin toxicity in several clinical studies. Possible mechanisms for the toxic effect of cyclosporin metabolites are covalent binding to macromolecules in liver and kidney, alteration of the cytochrome P450 pattern in liver and kidney, increased endothelin production in the kidney and synergistic effects of cyclosporin combinations on mesangial cells. Liver dysfunction leads to an alteration of the metabolite patterns and to increased concentrations of cyclosporin metabolites in blood. In conclusion there is evidence that cyclosporin metabolites may contribute to cyclosporin toxicity and high metabolite blood concentrations in patients should not be tolerated. PMID- 8361995 TI - Human high molecular weight-melanoma associated antigen mimicry by mouse anti idiotypic monoclonal antibodies MK2-23. Experimental studies and clinical trials in patients with malignant melanoma. AB - Following a description of the characteristics of the human high molecular weight melanoma associated antigen (HMW-MAA), the rationale to use anti-idiotypic (anti id) monoclonal antibodies (mAb) as immunogens to implement active specific immunotherapy in patients with malignant diseases is discussed. Among the anti-id mAb developed in this laboratory the mAb MK2-23, which had been elicited with the syngeneic anti-HMW-MAA mAb 763.74, has been shown with serological and immunochemical assays to bear the mirror image of the determinant recognized by mAb 763.74 on HMW-MAA. The anti-id mAb elicited humoral anti-HMW-MAA immunity in about 60% of patients with malignant melanoma. The immunogenicity of mAb MK2-23 is markedly enhanced by conjugation to a carrier and administration with an adjuvant, but is not affected by the administration of low doses of cyclophosphamide. Development of anti-HMW-MAA immunity in patients with malignant melanoma is associated with survival prolongation. These results in conjunction with the lack of major side effects in spite of repeated administrations of mAb MK2-23 suggest that active specific immunotherapy with mAb MK2-23 represents a useful therapeutic approach to malignant melanoma. PMID- 8361997 TI - Postmenopausal hot flushes and their management. AB - Hot flushes are frequently incapacitating to the patient and the severe vasomotor disturbances may seriously impair normal daily life. This review attempts to provide an understanding of the pathophysiology of the hot flush as a basis for rationale therapy for each individual patient. The physiological mechanisms controlling body temperature are discussed briefly, and the changes in the system which precipitate the menopausal hot flush are detailed. The neuroendocrine events leading to the onset of the flushing syndrome are then considered. Finally, the therapeutic strategies which may be used in the management of the affected patient are discussed. PMID- 8361998 TI - Cerebral vasoconstrictor mediators. AB - Endogenous cerebral vasoconstrictor mediators regulate vascular resistance and blood flow in the brain as a whole and in various regions and participate in the pathogenesis of cerebral circulatory disturbances. Vasoconstrictors are effective in the treatment of diseases associated with cerebral vasodilatation. There are variations in the response of cerebral arteries from primate and subprimate mammals; therefore, information as to similarities and differences in their response is quite important in evaluating the physiological role, involvement in pathogenesis and therapeutic usefulness of the mediators in healthy men and patients. In this review we described characteristics of the action of vasoconstrictors (amines, peptides, prostanoids, and others) on isolated cerebral arteries from mammals, including humans and monkeys. PMID- 8361999 TI - Cerebral circulation during diabetes mellitus. AB - Diabetes mellitus is characterized by hyperglycemia, a decrease in circulating insulin and the development of macro- and microvascular pathology. Hyperglycemia appears to be a primary determinant for the structural, biochemical and functional changes that occur in large and small blood vessels during diabetes mellitus. While much research has focused on the effects of diabetes mellitus on the peripheral circulation, it is clear that diabetes mellitus also has profound effects on the cerebral circulation. Thus, the focus of this review is to discuss morphological and functional alterations in the cerebral circulation during diabetes mellitus. PMID- 8362000 TI - [The "rete venosum plantare" (the plantar venous network or Lejars' venous sole of the foot)]. AB - Looking at the bibliography of the venous sole of the foot (Lejars), the authors point out the opposite convictions concerning this structure. For some ones, it doesn't exist, but fort the others, it is a very important network of tiny veins, such as it was described by Lejars himself. However, all this studies, are made upon cadavers, injected or not, and must be compared with results from living people by the mean of angiography, non invasive Vascular Assessment, or RMN, which take in account vasomotricity. PMID- 8362001 TI - [Lejars' sole. "A minimal network which secretes more saliva and ink than blood"]. PMID- 8362002 TI - [The superficial veins of the sole of the foot]. PMID- 8362003 TI - [The muscular pump of the foot: physiological and clinical importance]. PMID- 8362004 TI - [Phylogeny, verticalis and venous return in man. Various personal experimental Doppler ultrasound aspects]. PMID- 8362005 TI - [The epidemiology and socio-economics of venous diseases in Germany]. AB - The author reports the conclusions of a multicentre investigation lead in Germany. According to this study, varicose veins are more frequent in women than in men, either in ordinary population or in in-patients. Adults are not exclusively the only ones who suffer from varicose veins; children often suffer from them too. People suffer equally from phlebitis or post phlebitis syndromes. Moreover, heredity and obesity tend to favour this tendency. Thus, the socio economic impact is so important that the cost of treatment, hospitalization and the social cost of sick-leave must be taken into consideration. So, it is necessary for the Authorities to prevent venous diseases and be aware of the importance of phlebology. PMID- 8362006 TI - [Evaluation of an reference anatomo-clinical classification of varices of the lower limbs]. AB - In order to set up a common and objective language for everyone, the authors have laid the foundation of anatomoclinical classification which can be used as a reference in the study of varicose veins in lower limbs. They are comparing a group of patients with varicose veins to a control group of healthy patients. The groups are classified in four stages according to the importance of the varicose pathology and the histological characteristics. The conclusion is the following: there is no parallelism between these four clinical stages and the histological characteristics. According to the authors, it is necessary to make a distinction between fibrous reaction veins and muscular wall veins. This phenomenon is reported to have particular therapeutic implications in the prescription of substances of exciting venous tonicity. PMID- 8362007 TI - [The development of pre- and post-natal veins]. AB - Superficial and deep veins have different evolutions, structures and functions. Phylogenetically, superficial veins of limbs appear before the deep ones. In mammals other than man, both anatomical and histological abnormalities of superficial and deep veins have been noticed. In phlebology, the date of the first appearance of these veins was examined, from the infantile age to the age of 60 in 2,259 patients. Incomplete truncal varicose veins or an excess of certain perforating veins were found in 13.9% cases among children of school age. In 71.0% cases, these defects had a hereditary origin. PMID- 8362008 TI - [Instrumental research of the functional character of the skin adnexa and microcirculation during chronic venous insufficiency]. AB - We have led a microcirculatory and functional research of skin adnexa over 3 groups of 20 people each, who were affected with IVC at different grades and we have compared them to another group of 20 normal people. The microcirculatory researches (laser-Doppler, skin oximetry and thermometry) and functional ones of skin adnexa (sebometry and skin hydration) allowed us to get a nonunivocal behaviour between normal subjects and phlebopathies of I degree. For this reason, it is possible to consider these exams as screenings tests to determine the starting phases of phlebopathy, failing any skin marks. The reduced fluximetrical response taken by laser Doppler after postural variation and the reduction of hydration degree have been considered particularly significant. PMID- 8362009 TI - [Osteoporosis in phlebology]. AB - Patient often think that the pains of their extremities (especially during the night) are caused by a plebo or an angiopathy whereas they are in fact due to a vertebral or lumbar discal affection. 84 patients with osteoporosis were treated by an intramuscular injection of deca-durabolin (25 mg/month) and calcium phosphate (tertiare). Results were satisfactory: six months later, 62 patients no longer suffered, 13 had felt improvement and 2 remained unchanged. PMID- 8362010 TI - [Phlebology and podiatry]. AB - By their tensing and relaxation, the muscles of the leg are thought to be responsible for compressing and relaxing the vascular walls and the lumen of vessels. In order to study the way the muscle structure of the lower limb (in particular the leg and the foot) functions, it is necessary to understand the step and break down its components. The weight of the body is transmitted to the ground by the astralagus which distributes the different forces throughout the fives systems of ossei trabeculae of the astralagus and the heel. The valgus heel determines a continuous traction on the tendon and the hind leg muscle which determines with time a dragging of the foot. When the body goes forward, the weight levels the transverse fore arch. The flexor muscles of the toes bend the phalanxes, gripping them to the ground, they avoid the falling forward of the body with the proximal insertion on the tibia. The sesamoids increase the muscles power as well as that of the kneecap on the quadriceps. The internal curvature of the foot on the ground is furthered by the decreasing length of the metatarsal bones. This is counterbalanced by the long fibular muscle which lowers the medial axis and raises the external axis. The supination of the forefoot depends only in part on the varus valgus of the rear of the foot. The plantar aponeurosis and the flexor tendons have an impact on the metatarsi because they increase the power and bring the insert closer. The complex articular system of the feet depends on the extrinsic and intrinsic muscle structure which, at the same time as a position variation can also play an important part in the venous alteration. PMID- 8362011 TI - [The muscular pump of the calf. Video-phlebography and simultaneous EMG]. AB - Gastrocnemical insufficiency is a common syndrome (in modern society mainly affecting young females who have been taking the pill for several years). Often it is the starting point for superficial varicosis. The clinical diagnosis is easy, provided the doctor is informed of its symptoms. Phlebography or Duplex scan are compulsory, deciding surgical treatment. Varicose muscular veins have two different causes: avalvulation at the popliteal vein or compression by the Post. Tib. nerve. Persistent pain, deterioration of the superficial network or neuromyositis are the main reasons for deciding upon surgical treatment. The results are gratifying and lasting. PMID- 8362012 TI - [Loco-regional thrombolysis in deep venous thrombosis]. AB - Anticoagulation, by means of heparin and warfarin is, till now, the most common treatment in deep venous thrombosis. Although thrombolytic agents have been available for over 10 years, their use remains quite low, ranging from 15 to 20% of deep venous thromboses. This is due to the relatively high incidence of contraindications as well as to the fact that the potential advantages versus heparin are diminished by the increased bleeding risk and by the potential risk of pulmonary embolism (migration of partially lysed thrombi). Following the example of the "triple armed therapy" proposed by Rosenthal for the treatment of pulmonary embolism, we will evaluate if loco-regional thrombolysis, with the catheter wedged against the thrombus, associated with a temporary vena cava interruption by means of an intraluminal filter, can achieve a better lysis of the thrombus without pulmonary embolism. In our Unit 18 patients affected by proximal deep venous thrombosis were submitted to thrombolytic therapy, 6 to systemic treatment, 3 to local treatment and the last 9 to loco-regional thrombolysis, using recombinant tissue-type Plasminogen Activator. We obtained 10 complete lyses, 1 with systemic and 9 with loco-regional treatment. There were no major complications. Thus, we think that venous loco-regional thrombolysis with rt-PA at lower doses, associated with temporary caval interruption, can probably achieve a better lysis than systemic treatment without risk of pulmonary embolism and with a very low haemorrhagic risk, as in arterial loco-regional thrombolysis. Furthermore, loco-regional thrombolysis, by means of a faster thrombus dissolution, could better prevent post-phlebitic syndrome. PMID- 8362013 TI - [Venous insufficiency and varicose disease. Sequelae of lower limb thrombosis. The role of crenotherapy]. AB - The writers reminded that a consensus on Classification of veinous diseases, necessary to build up homogeneous samples, was being set up. Now, they are introducing a thermal nosology that is as useful. Next, the history of spas, the characteristics of Thermal Springs and thermal practices as well as their results are described. The writers present a standardization of the observation and control parameters of the therapeutic effects. The rigorous and scientific process was defined by an interdisciplinary scientific process was defined by an interdisciplinary scientific Council and it is based on the creation of a Computerized Laboratory of Research and a Thermal University. It has become an example in the field of thermalism. According to the results and the modern indications, the water cure has to be prescribed at an early stage. The practitioner must think about it and insert the water cure in the arsenal of veinous diseases. According to the hydrogeologists' estimates, BARBOTAN les thermes, the first European spa with about 22,000 patients is thought to possess enough water to allow from 40,000 to 60,000 people to be treated yearly. A thermal environment is the ideal place for an efficient vascular rehabilitation and functional re-education. In phlebology, more than one million people should benefit from a water cure yearly ... Only 70,000 follow this treatment. Everyone has to wonder about this situation, which, to those who do not benefit from a thermal cure in phlebology, is as astonishing as prejudicial. PMID- 8362015 TI - [Childhood difficulties: representations by the family and caregivers; value of interviews]. AB - This investigation was conducted in 7 consultation centers in child psychiatry of the Lyon region (France). The aim was to evaluate the influence of the care professional's response to the demands of the consulting party, on the evolution of the child. The investigation is based on what is said about the difficulties of the child, as manifested in the way care professionals, parents and children perceive them. Relevant instruments and a reliable methodology are used in assessing these various parameters. Results indicate that what happens in the first interview might be more important than the effective type of intervention in determining the evolution of the subsequent intervention. PMID- 8362014 TI - [Veno-lymphatic insufficiency. 4,729 patients undergoing hormonal and procyanidol oligomer therapy]. PMID- 8362016 TI - [Interactions of infants with adults in day care centers. Evolutive dependencies vs. counter-evolutive risks and characteristics of the mother-infant relationship]. AB - As part of a broader research project on the construction of the self, six infants were observed longitudinally in day-care centers between the ages of five months and three years. Interviews were conducted with the six mothers in order to evaluate the intersubjective characteristics of the mother-infant relationship. For three of the six children, the mother was a caregiver in the center. This article deals with "propping" processes, defined as the affective cognitive transformations by means of which infants develop networks of links with and between external and internal objects which are used for support during development and serve as a relay of the maternal object. The present analysis is limited to propping on the adults in the day-care center (caregivers, observer, and, for three of the children, mothers). Two factors were considered: the intersubjective quality of the mother-infant relation, and the presence or absence of the mother as a caregiver in the day-care center. The results showed that (1) even when very young, the infants under observation differentiated between the various functions of the adults, and adapted their behavior to them; (2) each child exhibited a unique and sometimes very creative way of using dependencies on an adult's psychic apparatus to construct his or her own modes of psychic functioning; and (3) the developmental dynamics and the richness of the observed transformations were found to depend on the quality of the contact and distancing in the mother-infant relationship and on the concrete conditions for its actualization, which can either promote or hinder, and sometimes even block, the construction of the mother's absence. PMID- 8362017 TI - [Characteristics and functions of friendship in adolescence]. AB - This article reviews recent studies which have examined various aspects of friendship relations in adolescence. Friendship relations are of central importance in the social life of adolescents because they assume a crucial role in certain developmental functions: emancipation from parental guardianship, commencement of heterosexual relations and affirmation of one's identity. This article reports on various aspects of friendships in adolescence: number of friends, places of recruitment, frequency of meetings, and common themes of conversations. Friendship relations are relatively conflict free in adolescence. They can be characterised by three main elements: trust, communication and intimacy. Friendships evolve in adolescence from a common interest in activities to a sharing of opinions, emotions and feelings. At all ages, girls value the elements of friendship more than boys. In the last ten years research has demonstrated that there is a correlation between adolescent friendship, coping mechanisms, and the acquisition of social skills. The quality of friendship relations and particularly the ability to communicate personal worries predicts this correlation better than the number of friends. The research in the field of friends versus parent influence has abused the concept of peer pressure in committing delinquent crimes. Indeed there is a great deal of agreement between parents and friends in terms of moral values and academic and vocational aspirations. The influence of friends predominates only when there are severe conflicts between parents and their children. PMID- 8362018 TI - [Malaise in teachers]. AB - A lot is said about present days sense of disarray in teachers. How real is the fact? How come the debate on education is so passionate? Why such shortsightedness in society's vision of its educational system? There truly is happiness in teaching, and this happiness can evolve out of the worst hardships. Nevertheless that happiness is fragile. It is threatened by situational factors and some may be tempted to adopt identity assertive behaviors. Moreover, achieving that happiness might be costly to the individual: situations area often hard on the narcissism, and frequently provoke deceptions proportionate to the moments of complicity shared with the children and adolescents, who reflect passing illusions of what teachers themselves were. PMID- 8362019 TI - [Post-partum blues: a critical review of the literature]. AB - The abundant literature dealing with the post partum blues has failed to describe a possible causing factor in these emotional and physical manifestations which are frequently observed in mothers during the first few days following delivery. The post partum blues has been considered as a promising model for depressive states but its function has never been clearly established. No agreement has been reached as to its physiological mechanism. Presently there is a renewed interest for the "third day blues" in relation to post-birth depression, which is known to be frequent, and to the early interactions. The authors present a review of the literature and emphasize the necessity to approach this issue from a new standpoint and with new conceptual and measurement tools. The role of post partum blues could well be, through a biological process involving the dopamine, to facilitate the establishment of early mother-infant bonds by provoking a decrease in blunted affect. PMID- 8362020 TI - [Cognitive disorders and psychiatric manifestations in the fragile X syndrome. Autism and fragile X]. AB - The fragile X syndrome is one of the main etiologies of mental retardation in human beings. Some of its specific cognitive and language disturbances are nowadays well known. Disturbances of behavior are frequent. They are akin to psychotic manifestations and are mainly described in terms of autistic syndromes. The question of the possible links between autism and the fragile X syndrome is being discussed since 1980. The authors give a synthetic and critic overview of the studies reporting on the frequency of co-occurrence of these syndromes and offer some reflexion on the true questions at stakes in the debate. They emphasize the determining role of future clinical research in autism in order to objectively contribute to the progression of knowledge in this field. PMID- 8362022 TI - [Dual diagnoses: addiction and other psychiatric disease. Theory, empirical findings and basic therapeutic considerations of a new concept]. AB - A special group of psychiatric patients appeared during the last few years; patients who confront their therapists with many diagnostical and therapeutic problems, namely patients with dual diagnosis. These patients suffer from a severe psychiatric illness (such as schizophrenia) and at the same from an addition (e.g. an alcohol-dependency). The management for patients with dual diagnosis is inappropriate as well in psychiatric units as in specialized addition units. Today specialized units for patients with dual diagnosis are non existent in Switzerland. The following review presents theoretical implications, empirical data and therapeutic possibilities for patients with dual diagnosis. PMID- 8362021 TI - [New point of view on psychosis. Psychosis, death, and family]. AB - Without denying relevance to previous postulates related to psychosis, the author proposes to view psychosis in the extended context of the immediate family and its generations. After recalling prior literature on overmortality in psychotic patients, on the role of psychic transmission from one generation to the other in the genesis of psychosis, and on the offsprings of families with psychotic members, the author presents the results of her own research: occurrence of psychosis in a family is frequently associated with the death of one or more children among the siblings, and with a tendency towards extinction of the family branch to which the psychotic subject belongs. PMID- 8362023 TI - [The aggressive patient--comments on the social psychology of violence]. AB - The management of the violent patient in hospital requires highly skilled therapeutic staff. Prevention, restriction and therapy of aggressive behaviour needs adequate diagnosis and therapy of the underlying disorder, furthermore a well structured ward milieu. This study pays attention to maladaptive structuring of the therapeutic milieu, which interferes with the integration of the violent patient. Modernized psychiatric institutions with liberal administration tend to expel the troublesome, especially the violent patient, when the formal organization of the institution superstructure is weakened. PMID- 8362024 TI - [Improving the ward atmosphere on the acute psychiatric unit]. AB - Patients and nurses assessed the social atmosphere in two psychiatric acute care units and their behavior was recorded before and after the observation ward and the residential ward were transformed into two fully functioning admission wards, avoiding transference of patients. Consequently, the initially high amount of isolated behavior decreased, social behavior and outdoor activities increased. For the patients, however, the stereotype of a psychiatric acute care unit does not change so soon because of their higher aspiration levels and their uncertainty about the treatment concept. As the new structures increasingly are filled with life, "environmental therapy" aimed at the patients' involvement gains a great importance. PMID- 8362025 TI - [Psychotherapy in the psychiatric institution--on therapy at the other pole of the diagnostic spectrum]. AB - In psychiatric facilities we treat patients with severe disturbances under conditions which do not fulfill what are generally thought to be the necessary ingredients of psychotherapy. Additionally our staff tend to devalorate themselves by thinking that in fact they should work differently that, what they do, was actually not real psychotherapy. The present paper shows with concrete examples what is psychiatric psychotherapy, it asks what are the needs of severely ill patients, and concludes that this difficult work is real psychotherapy in the best sense of the word. PMID- 8362026 TI - [Psychotherapeutic ambulatory care of a psychiatric department in a general hospital]. AB - This is a survey of the treatment courses provided so far during the initial period after the foundation of a psychotherapeutic outpatient ward of a Department of Psychiatry in a General Hospital. A relatively small benefit only is actually derived from this institution by the Department of Psychiatry: this benefit consisting of the fact that inpatients requiring psychotherapeutic treatment can be referred quickly to outpatient treatment in the psychotherapeutic ward. As a matter of fact, however, the outpatient ward barely fills the considerable gap in psychotherapeutic facilities available in the city of Oberhausen in Germany, whereas on the other hand adequate financial sponsoring has not been satisfactorily assured to date. Almost half of the referred patients were unsuitable for the depth psychology treatment offered by the outpatient ward and had therefore to be ruled out. PMID- 8362027 TI - [Disordered coping with illness by personal prejudices of patients with schizophrenic psychoses]. AB - Negative prejudices against psychiatry and psychiatric patients are a reality today. But prejudices are also existent in the patients self, especially in schizophrenic patients, leading to adverse therapeutic reactions. Prejudices of the patients himself may be a hidden, unconscious problem in some cases of treatment resistance in rehabilitation of schizophrenic patients. Therapeutic strategies are discussed on the basis of case reports. PMID- 8362028 TI - [5 years "cognitive training" in a psychiatric district hospital--a report of experiences]. AB - In a big psychiatric hospital we began 1987 to practice cognitive training with our patients after teaching this therapy to male and female nurses. Now we report how this project found its development, which overall experiences there were made and which corrections still have to be done. PMID- 8362029 TI - [Wagner von Jauregg and development of malaria therapy]. AB - In this history of psychiatric therapy the progressive paralysis deserves special interest: for the first time an organic psychosis was treatable successfully by a procedure found by scientific methods. This article describes life and work of Julius Wagner, Ritter von Jauregg (1857-1940) and remembers the introduction of the malaria-therapy, which was developed by Wagner 75 years ago. PMID- 8362030 TI - Society for Psychophysiological Research. 33rd annual meeting. October 27-31, 1993. Rottach-Egern, Germany. Abstracts. PMID- 8362031 TI - Anecdote beats out science-popular but unfortunate. PMID- 8362032 TI - Biologic problems of the light-cured composite resin. PMID- 8362033 TI - Single discolored tooth: an alternative treatment approach. AB - A single discolored tooth is often difficult to treat, but one with an obliterated pulp chamber and root canal presents an even greater challenge. The use of nightguard bleaching is offered as a simpler, alternative treatment to either root canal therapy or the removal of sound tooth structure for fabrication of a facial veneer or a complete-coverage crown. PMID- 8362034 TI - Extending the use of rubber dam isolation: alternative procedures. Part III. AB - This paper, the third of series, describes additional modified rubber dam utilizations that are generally not attempted with restrictive orthodox application methods. Part III offers practical hints and other means of retention with the emphasis on pedodontic applications. PMID- 8362035 TI - The removal of restorations and foreign objects from root canals. AB - A review is presented of some of the techniques available for removing restorations and foreign objects from root canals. Consideration is given to the removal of root restorations, sealers, and root canal obstructions, including fractured instruments and intact or broken posts and cores. PMID- 8362036 TI - The ideal dental photographic system. AB - After the limitations of dental camera systems with regard to their lens and their flash unit are explained, a point-ring-flash combination is presented. The flash was tested in practical use and by systematic test shots. The flash combination allows the dentist to use a point flash or a ring flash alternatively. Nearly all problems in dental photography can be solved by using this equipment. PMID- 8362037 TI - Geriatric prosthodontics: an overview. Part I. Pretreatment considerations. AB - A rising geriatric population remains dentate and requires more dental care to maintain dental health and function. This article discusses psychological aspects of aging and considerations of age-related changes of teeth, oral tissues, nutrition, and metabolism in the elderly. Aging affects all tissues and systems, as do nutritional and metabolic factors. Numerous factors alter healing, host resistance, digestion and absorption, mastication, metabolic competency, renal and hepatic function, and excretory capability. Complex drug regimens further confuse clear diagnoses. Full consideration must be given these factors before treatment plans are formulated. PMID- 8362038 TI - Attitudes to identification of dentures: the patients' perspective. AB - The importance of placing identification marks on dentures has long been acknowledged by the dental profession. More recently, following the fatalities at the Bradford City, England, football club fire, the need for marking dentures has been made more public. This paper outlines the different types of marking systems available and describes a survey on denture wearers to investigate their attitude toward the placement of identification marks on dentures. Results show that few dentures are marked at manufacture but that wearers are in favor of having their name on their denture. Of the 63 subjects sampled, 93.5% did not know that identification marks could be placed on dentures. The profession must be encouraged to routinely label all dentures at manufacture. PMID- 8362039 TI - Bond strength of dentinal adhesives in primary teeth. AB - The purpose of this project was to test the in vitro bond strength of three dentinal bonding agents to primary dentin. Scotchbond 2, All-Bond, and Amalgambond were applied to 63 teeth according to manufacturer's instructions. Valux composite resin was placed in a cylindrical matrix and light cured to the treated dentin. After they were thermocycled for approximately 800 cycles between 6 degrees C and 60 degrees C, the specimens were mounted in stone and placed in an Instron universal testing machine. They were placed under continuous load until failure. Fracture was at the dentin-bonding agent interface for all materials tested. Incisor bond strength was significantly stronger than molar bond strength for all three materials. Materials analysis revealed that the mean bond strength for Scotchbond 2 (6.99 MPa) was significantly different from those of All-Bond (13.01 MPa) and Amalgambond (13.03 MPa). PMID- 8362040 TI - Trismus appliances and indications for use. AB - Trismus is a condition that impairs eating, interferes with oral hygiene, restricts access for dental procedures, and may adversely affect speech and facial appearance. The success of treatment depends on recognition of the cause and initiation of appropriate management. Ideally, trismus appliances are used in conjunction with physical therapy and are most effective when the condition is the result of muscle fibrosis or scar tissue that has not yet matured. Trismus appliances act either externally or internally, and the forces they impart can be continuous or intermittent, light or heavy, and elastic or inelastic. Six appliances have been described in the literature. A seventh appliance, a plastic tapered cylinder, is also effective. The tapered cylinder relies on the patient's depressor muscles to separate the jaws, and allows easy appreciation of the progress made. The stretching force applied with this appliance is limited by the strength of the patient's depressor muscles. PMID- 8362041 TI - An in vitro study of parameters related to marginal and internal seal of bonded restorations. AB - The wall-to-wall contraction of the cementing layer of bonded restorations is compensated for mainly by elastic and plastic tooth substrate-cement deformation but may result in adhesive fracture. Occlusally flattened teeth and corresponding computer-designed onlays, both positioned in a special device, were used to study marginal and internal seal of the adhesive interface with respect to four variables: rigidity of the restoration-substrate setup, cement thickness, adhesive configuration (enamel-dentin ratio and bonding agent), and luting agent. The results of dye infiltration tests revealed the significant influence of the adhesive configuration and rigidity of the setup. A high enamel-dentin ratio, use of a dentinal adhesive on dentinal margins and relative restoration-substrate "mobility" are required to preserve satisfactory marginal seal. However, in the present experimental conditions, no statistically significant differences were found among the diverse cement thicknesses or the luting agents evaluated. PMID- 8362042 TI - Shade selection and laboratory communication. AB - This article reviews some of the factors involved in shade selection for prosthetic teeth and suggests simple techniques for accurately transmitting information about the desired color to the laboratory technician. PMID- 8362043 TI - Custom ceramometal pontics in a Kennedy Class IV maxillary removable partial denture: a clinical report. AB - A technique in which the custom-made anterior ceramometal pontics are securely attached to the metal framework of a Kennedy Class IV removable partial denture is described. This technique results in a more esthetic prosthesis with less palatal coverage. PMID- 8362044 TI - Periodontal surgical techniques used to conserve maxillary anterior esthetics. AB - The maxillary anterior region presents a difficult and unique therapeutic challenge in the treatment of periodontal disease. The periodontist should use therapeutic procedures to prevent or minimize esthetic problems, such as increased tooth length and loss of interdental papilla, without compromising the main goals of periodontal treatment. This article presents various periodontal treatment modalities that can be used in the anterior maxillary area with acceptable esthetic results. A better understanding of the problem, the treatment steps, and the various options available may improve the communication between the general practitioner and the periodontist, producing satisfactory long-term results. PMID- 8362045 TI - Adhesive restoration of an endodontically treated incisor. AB - Glass-ionomer cement and composite resin can be used in combination for restoration of an endodontic access preparation. Adhesive restorations using these materials avoid the problems of marginal leakage and tooth discoloration, characteristic of silver amalgam restorations, and preclude the need for complete coronal restoration. A detailed clinical procedure for placement of a stratified glass-ionomer cement and composite resin restoration for an endodontically treated permanent incisor is described. PMID- 8362046 TI - "Killer" canine removal and its sequelae in Addis Ababa. AB - Children and adolescents, aged 2 to 18 years, from 300 poor families in Addis Ababa were examined to determine the prevalence of the traditional practice of primary canine tooth removal. Fifteen percent of the primary canine teeth were found to have been affected, and 7% of the permanent canines had been damaged by this practice. A questionnaire to a subset of 40 families revealed some of the reasons that this procedure is still carried out, in spite of the considerable associated morbidity. PMID- 8362047 TI - A radiographic study of aging changes of the dental pulp and dentin in normal teeth. AB - One aspect of a previous retrospective radiographic study was an examination of diameter and length changes of root canals at various ages. It was found that root canal shrinkage increased with advancing age. In the present follow-up study, a larger population (500 subjects) was used and only mandibular anterior teeth were evaluated. Root canal shrinkage was calculated vertically and horizontally. Measurements taken were tooth length, coronal length, apical length, root canal length, cervical width, midroot width, and apical width. Six age groups were examined: 17 through 29; 30 through 39; 40 through 49; 50 through 59; 60 through 69; and 70 through 79. Root canals showed statistically significantly more shrinkage with advancing age; there were significant changes among all groups. These findings could prove useful in anthropology and forensics and as an aging biomarker. PMID- 8362048 TI - Bonding durability of photocured phenyl-P in TEGDMA to smear layer-retained bovine dentin. AB - The long-term durability of a photocured resin bond to ground bovine dentin with its smear layer retained was investigated. The bonding resin that was employed was composed of 5.0 wt% 2-(methacryloxy)ethyl phenyl hydrogen phosphate (phenyl P) as a diffusion-promoting monomer, 0.5 wt% camphorquinone as a photosensitizer, and 0.5 wt% N-phenylglycine as a reducing agent in triethyleneglycol dimethacrylate. Following polymerization of the bonding resin, a composite resin was placed and photocured for 60 seconds. Prepared specimens were stored in 37 degrees C water for 1 day, 6 months, and 1 year. Measured tensile bond strengths were 6.7 MPa after 1 day of storage, 4.1 MPa after 6 months of storage, and 2.8 mPa after 1 year of storage. Examinations of the interfaces after fracture under tensile loading suggested that long-term water-immersion weakened the bonds between the photocured adhesive resin and the smear layer-retained dentin because there was insufficient diffusion of the adhesive resin through the retained smear layer. PMID- 8362049 TI - Assessment of local side effects of casting alloys. AB - A retrospective survey was performed to assess side effects of alloys used in fixed and removable partial prosthodontics. Nineteen clinicians reported the status of prosthodontic appliances that had up to 31 years of service and the reactions in the corresponding oral mucous membrane. Survey charts of 335 patients, who had a total of 915 fixed and 87 removable prosthodontic units, were received. Almost half of these prostheses were made from base metal alloys, mainly nickel-chromium alloys for the fixed partial dentures, and cobalt-chromium for the removable partial dentures. The rest were classified as gold and palladium-type alloys or as miscellaneous. There were no or only slight deviations from the normal uniform luster of the metal components in all groups. Only four units were reported to have moderate reactions of severe tarnish and signs of corrosion. The gingiva and oral mucosa adjacent to the restorations were normal but showed slight changes in all groups. Twenty-three of the 335 patients were reported to have moderate reactions, and two patients had severe reactions. The soft tissue reactions were considered to be largely due to factors other than the metal components. PMID- 8362050 TI - Geriatric prosthodontics: an overview. Part II. Treatment considerations. AB - This two-part paper discusses treatment considerations for geriatric patients--a population that is on the rise. The first part of this paper examined the effects of aging on general health and on the oral environment. The second part discusses restorative treatment options for geriatric patients with caries, tooth wear, or missing teeth. PMID- 8362051 TI - Herpetic whitlow. AB - This paper describes a case of transmission of herpetic whitlow to the index finger of a dental student from a patient with herpes simplex virus. The recognition of intraoral viral infections in patients is important because these viruses have serious implications for health care providers. Rubber gloves must be worn when patients with primary or secondary herpetic lesions are treated. Asymptomatic permanent herpes virus carriers must also be treated with appropriate precautions. PMID- 8362052 TI - Role of magnetic resonance imaging in hyperparathyroidism. AB - Magnetic resonance imaging is indicated for the localization of the abnormal gland or glands in patients with recurrent or persistent hyperparathyroidism. The accuracy of MRI is equivalent or superior to thallium subtraction scans and high resolution ultrasonography for identifying the abnormal glands in the neck and superior to other noninvasive imaging techniques for recognizing ectopic glands in the thorax. Most glands have low to medium intensity on T1-weighted images and high intensity on T2-weighted images; however, glands with unusual signal intensity characteristics occur infrequently. Abnormal glands have shown considerable enhancement on T1-weighted images after use of gadolinium DTPA. Some pitfalls in the identification of abnormal parathyroid glands are now recognized. PMID- 8362053 TI - Practical considerations in the scintigraphic evaluation of endocrine hypertension. The adrenal cortex and medulla. AB - A nuclear scan maps the distribution of a radiopharmaceutical that is specific for a physiologic property of a targeted tissue. As such, it is not limited by the anatomic changes necessary for CT and MR scans. It is just because of this that maps of specific metabolic precursors of adrenal medullary and cortical hormones offer information crucial to the therapeutic strategy of endocrine hypertension. NP-59 and MIBG scans can specify the nature of abnormalities revealed by anatomic images and because of the ease of surveying the whole body can give transcendent information about lesions remote from the adrenals. In instances when the origin of endocrine hypertension is not forthcoming from CT or MR imaging or when the anatomic and biochemical findings are in conflict, NP-59 or MIBG can almost always provide the answer. PMID- 8362054 TI - The dilemma of bilateral adrenocortical nodularity in Conn's and Cushing's syndromes. AB - Bilateral adrenal nodularity in Conn's and Cushing's syndrome leads to a more complex differential diagnosis than the presence of a unilateral mass or bilateral hyperplasia. In Conn's syndrome, bilateral nodularity is not synonymous with hyperplasia, and adrenal venous sampling is required to detect those cases of surgically correctable aldosteronoma. In Cushing's syndrome, bilateral nodularity can result from an ACTH-dependent or an autonomous adrenal cause of hypercortisolemia. The appropriate therapeutic decisions depend on the recognition of these different entities. PMID- 8362055 TI - Endocrine angiography and venous sampling. AB - Localization procedures are performed only after the diagnosis of endocrine disease is established. Arteriography and venous sampling may be essential to locate a small hyperfunctioning endocrine tumor or to assist in distinguishing between disease caused by a solitary tumor and disease caused by diffuse hyperplasia. These procedures require a detailed knowledge of vascular anatomy and must be performed meticulously to avoid incorrect results. Close cooperation between the radiologist and the endocrinologist is essential for optimal results. These procedures are complex and are rarely performed outside of the few centers where endocrine problems are frequently evaluated. In many cases, the patient may be best served by referral to an institution where these radiologic studies are routine. PMID- 8362056 TI - Adrenal, pancreatic, and scrotal ultrasound in endocrine disease. AB - Ultrasound is an ancillary tool in adrenal imaging in adults and a primary tool in children. Intraoperative sonography is the method of choice for pancreatic endocrine tumors. In the scrotum, the benign adrenal rest tumors must be distinguished from the more common malignant mass. PMID- 8362057 TI - The ovary. Computed tomography and magnetic resonance imaging. AB - CT and MR imaging can both contribute valuable clinical information in women with benign and malignant ovarian masses; the superior soft tissue contrast and multiplanar capabilities provided by MR imaging make it a valuable tool to evaluate the normal ovary, polycystic ovaries, endometriosis, and disorders of sexual differentiation. CT is currently the recommended modality to stage ovarian carcinoma, and peritoneal implants as small as 5 mm can be visualized. With the addition of contrast-enhanced images to conventional MR sequences, however, improved visualization of intratumoral architecture has also allowed for accurate MR characterization of benign versus malignant ovarian masses. Fat saturation techniques used with conventional MR sequences can also be used for definitive characterization of benign fat-containing teratomas and differentiate these tumors from hemorrhagic ovarian cysts or endometriomas. Finally, the detailed visualization of the normal-sized ovary on MR images provided by both the body coil and the new phased-array coil allows detection of the normal ovaries, ovarian follicles, and ovarian cysts throughout the premenopausal and postmenopausal years. Findings of polycystic ovarian syndrome, which cannot be evaluated by CT, are characteristic on MR images. MR is unparalleled in the evaluation of disorders of sexual differentiation because MR images can depict ectopic and normally positioned gonads and provide multiplanar depiction of the other pelvic organs and perineum as well. CT and MR imaging can provide valuable and specific clinical information about the ovary and benign and malignant ovarian disease. PMID- 8362058 TI - Radiologic diagnosis of osteoporosis. Current methods and perspectives. AB - Osteoporosis is defined as a decrease in bone mass accompanied by structural changes, leading to an increase in fracture propensity. Early diagnosis of osteoporosis, fracture risk prediction, and assessment of efficacy of therapy therefore are of great interest. A number of noninvasive techniques are available for measuring bone mass at multiple sites of the skeleton. This article reviews basic methodology and developments in radiology such as x-ray and photon absorptiometry and quantitative computed tomography, which are routinely used in clinical practice. Recent techniques for assessment of bone mineral density and structure, such as ultrasound measurements, and their possible clinical applications also are discussed. PMID- 8362059 TI - Hypothalamic and pituitary pathology. AB - This article details the intricate anatomy and elegant physiology of the hypothalamic-pituitary axis. The discussion is meant to confer an understanding of the principles of neuroendocrinology appropriate for the radiologist interpreting imaging studies of this region. The clinical presentations of the diseases that occur in this area of the central nervous system are unique and therefore are discussed in some detail. The radiologic features of the diseases affecting the hypothalamic-pituitary axis are described and correlated with the relevant pathology. PMID- 8362060 TI - Radioisotopic evaluation of the thyroid and the parathyroids. AB - Since the inception of the discipline of nuclear medicine, thyroid evaluation and therapy with radioactive isotopes have remained an important and constant component of thyroidology. Parathyroid scintigraphy with 201Tl/99mTc subtraction has been a more recent and also very useful addition in the assessment of hyperparathyroidism, particularly at reoperation. The radioactive iodine uptake test gives important metabolic information on thyroid function in such diverse disease states as hyperthyroidism, hypothyroidism, the thyroiditides, and thyroid carcinoma. Thyroid scintigraphy is also a key contributor to the assessment of patients with hyperthyroidism or with single versus multiple thyroid nodules, those with a history of head and neck irradiation during childhood, and those requiring diagnostic follow-up studies with 131I after total thyroidectomy for differentiated thyroid carcinoma. Each of these topics is reviewed and expanded on in this article, with a diversity of illustrative scans provided to complement the discussion. PMID- 8362061 TI - Learning contracts in clinical education. AB - This study explored the outcomes of using learning contracts in a radiologic science program. Telephone surveys of contract learning participants and other radiologic science graduates provided data regarding graduate career satisfaction, lifelong learning habits and attitudes toward learning. Statistical comparison data found that contract learning participants reported higher job satisfaction, participated more in continuing education, demonstrated more self motivation and independence, felt less competitive and anxious about courses and grades and felt more involved in their clinical courses. PMID- 8362062 TI - RTs performing venipuncture: a survey of state regulations. AB - Venipuncture is an Essential component for nuclear medicine technologists and is expected to become an Essential for radiographers. A descriptive survey of radiation safety offices in the 50 states and the District of Columbia was conducted to determine which states license or certify nuclear medicine technologists, radiographers and/or radiation therapists and to identify specific statutory terminology relative to drug administration or venipuncture. Results showed only six states specifically addressed the issue of drug administration or venipuncture for radiographers and radiation therapists. With so few states addressing this issue, the question arises whether technologists who perform venipuncture or administer drugs are protected against litigation for performance of these procedures. PMID- 8362065 TI - Nurse opines on non-natural childbirth: freedom of speech. PMID- 8362064 TI - Treating the adolescent cancer patient. PMID- 8362063 TI - Indicators of potential success among radiography students. AB - As the demand for qualified radiographers grows and the number of applicants to schools far exceeds the available capacity, program directors across the country face increasing difficulty in screening candidates for admission. This study sought to determine if there was a significant correlation between high school class rank, Scholastic Aptitude Test scores and the successful completion of a radiography curriculum as measured by a passing score on the American Registry of Radiologic Technologists examination. PMID- 8362066 TI - Nurse refuses to "stay out of it": termination. Case in point: Kirk v. Mercy Hosp. Tri-County 851 S.W. 2d 617--MO (1993). PMID- 8362067 TI - Legal case briefs for nurses. GA: failure to monitor intubated patient: "physician testimony" on nursing standares; FL: Board adopts Dr.'s "surgical care rule": nurses lack standing at hearings. PMID- 8362068 TI - Age Discrimination Act violation charged: "constructive discharge". Case in point: Clowes v. Allegheny Valley Hospital 991 F. 2d 1159--PA (1993). PMID- 8362069 TI - Aspects of protein energetics and dynamics. PMID- 8362070 TI - Psychoneuroendocrine assessment of posttraumatic stress disorder: current progress and new directions. AB - 1. Studies in our laboratory have used the psychoendocrine strategy to explore differences in basal hormone levels between patients with posttraumatic stress disorder (PTSD) and other groups. This approach has allowed us to explore the relationship between hormone levels and specific psychological and biological processes which appear to develop following exposure to extreme trauma. 2. The concurrent assessment of several hormonal systems provides an opportunity to explore differences in hormonal patterns in various psychiatric disorders. PTSD appears to be characterized by a specific profile of hormonal changes that is distinct from that of other diagnostic groups and normal controls. These findings raise the possibility that the psychoendocrine approach may be useful in further exploring the pathophysiology and diagnosis of PTSD. 3. This paper reviews psychoendocrine changes in PTSD and describes updated multivariate methods that further elucidate psychological and neurochemical correlates of hormonal alterations in this disorder. PMID- 8362071 TI - Course and outcome in panic disorder. AB - 1. Panic disorder (PD) is an illness that can be acute or chronic and is often complicated by depression, phobias and obsessions. This illness affects at least 10% of the population. 2. Panic disorder has been recognized as a psychopathologic condition for at least 100 years. Over the last several decades, health professionals have changed their view of PD, and in 1987 the DSM-III included PD as a distinctive syndrome. 3. Several studies have shown PD to be a chronic illness with only little to no improvement in 36-40% of the subjects after 1 to 20 years of treatment. Studies also suggest that duration of illness affects the degree of impairment: subjects who had PD for more than 6 months showed more impairment that subjects who had PD for less than 6 months. 4. Several studies show that 50-75% of patients with PD have had at least one episode of major depression. Findings also indicate that subjects with both PD and secondary depression are a more severely ill group. 5. The HARP study is an ongoing 12-site naturalistic, longitudinal examination of patients with current or past PD. One of the major goals of this study is to describe the patterns of the clinical course of PD related disorders. 6. Clinical experience indicates that an estimated 40% of PD patients may need treatment for one year and between 20-40% will require continued maintenance treatment. Long-term treatment may include behavioral therapy and/or medication. 7. Anxiety disorders are common and familial and are consistently higher among women. Panic Disorder is a chronic condition frequently complicated by Axis I and II disorders. Continued long-term maintenance studies of medications and psychotherapy for anxiety disorders is critical in the treatment of this chronic illness. PMID- 8362072 TI - Neuroendocrine and psychosocial mechanisms in post-partum psychosis. AB - (1) Results from a study investigating psychosocial and neuroendocrine influences on post-partum psychosis are presented. Subjects were 43 pregnant women with histories of affective disorder (bipolar or schizoaffective disorder, n = 26; major depressive disorder, n = 17), together with 45 pregnant women without any psychiatric history. (2) At 36 weeks antenatal assessments were carried out of the women's psychiatric histories, current psychiatric state and also the occurrence of life events in the preceding year. They were then monitored for 6 months after delivery during which time psychiatric state and any further life events were recorded. Illness was defined according to Research Diagnostic Criteria (RDC); 22 high risk women and 3 control women were categorised as RDC 'cases' during the post-partum follow-up period. Fifteen of the bipolar/schizoaffective women (8 of whom subsequently became ill within 3 months of delivery) and 15 controls (all of whom remained well) also participated in a neuroendocrine test at 4 days post-partum when their growth hormone response to a challenge dose of the dopamine agonist, apomorphine, was measured. (3) The results showed that women with histories of depression and control women who became ill after delivery were three times more likely to have had a life event in the year preceding onset of illness than women from these subgroups who remained well. In contrast, for women with histories of bipolar or schizoaffective disorder, life events appeared to be unimportant. Instead bipolar/schizoaffective women who became ill showed an enhanced growth hormone response to the apomorphine challenge test compared to those who remained well and controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362073 TI - Cognitive performance as modified by age and ECT history. AB - 1. Cognitive processing, as measured by 15 subtest from the Wechsler Memory Scale (WMS) and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) was assessed in 109 depressed inpatients who were classified as under age 65 (N = 54) or 65 or older (N = 55). Within each age group, patients were further classified according to whether they had no prior ECT (N = 40), one prior ECT series (N = 37), or two or more prior series of ECT (N = 32). 2. After examining the data set for possible sources of bias such as group differences in the severity of depression, time since last ECT series, unilateral vs. bilateral electrode placement, adjunctive use of psychotropic medication, gender, education and so forth, a MANCOVA and a series of 15 two (age) by three (ECT history) by two (gender) analyses of covariance (education served as the covariate) were used to examine the main effects of ECT history, age and their interaction on cognitive performance. 3. No generalized adverse effects of prior ECT treatment were found but older patients with two or more prior ECT series performed significantly more poorly than other subgroups on 4 of 15 cognitive tests: (1) Personal and Current Information from the WMS, (2) WMS Stories recall, (3) 30-minute delayed WMS Stories and (4) WAIS-R Similarities. 4. These findings suggest that the verbal narrative memory functioning of depressed geriatric patients with a history of at least one prior ECT series is particularly vulnerable to disruption. PMID- 8362074 TI - Histories of substance abuse, panic and suicidal ideation in schizophrenic patients with histories of post-psychotic depressions. AB - 1. Forty patients who had had syndromally-defined episodes of post-psychotic depression at least 6 months previously were interviewed in detail for life-time histories of substance abuse, panic attacks, and suicidal ideation. 2. No relationship was found between life-time history of suicidal ideation and substance abuse. 3. Statistically significant associations were found between lifetime history of suicidal ideation and both a life-time history of panic attacks and the panic disorder syndrome. PMID- 8362075 TI - TRH test in psychiatric research. PMID- 8362076 TI - ["Mother" and "father" in psychoanalytic case vignettes. On some latent rules in the discourse of psychoanalysis]. AB - Proceeding from the conviction that there is a collective gender-specific unconscious within the community of psychoanalysts which determines latent rules operative in psychoanalytic discourse, the authors have conducted a research project extending over a number of years and systematically examining case descriptions in psychoanalytic journals to see to what extent those latent gender specific rules are in fact observed in such publications. The project examines the way in which male and female analysts employ the terms "mother" and "father" in these publications and also the frequency and connotations of concepts related to "mother" and "father". Significant differences between male and female analysts become apparent, substantiating the assumption of a collective gender specific unconscious. The authors conclude that this unconscious finds its way into psychoanalytic therapy, leading to unconscious counter-transference reactions that are acted out rather than worked on. PMID- 8362077 TI - [The son of man. Freud's Oedipus myth]. AB - In formulating his psychology of the unconscious, Freud makes constant reference to Sophocles' version of the Oedipus myth. The author provides detailed proof of the fundamental differences between the two versions, demonstrating that Freud's interpretation does violence to the source. Bollack marshals impressive evidence to substantiate his contention that from the early letters to Fliess all the way up to Moses and Monotheism Freud's sole concern was to point up the ubiquitous power of the unconscious (incestual desire, patricide) within the "holy" (nuclear) family, whereas Sophocles was preoccupied with an entirely different problem. In Bollack's view, Oedipus rex is the drama of the self-destruction of a royal family, a drama in which incest and murder have no very essential significance. Freud, by contrast, set out to de-mystify the fate that dogs the royal family from one generation to the next and to naturalise it into a form of unconscious behaviour--a tendency which Bollack sees as deriving from the tradition of the "drama of destiny", a genre prevalent in the 19th century. PMID- 8362078 TI - [The driving force in the thinking of Norbert Elias. An attempt at psychoanalytic interpretation]. AB - The theory of civilization proposed by the eminent sociologist Norbert Elias, who died in 1990, has its roots in Freud's theory of culture. Elias always denied the importance of personal factors in connection with his work, but as has been demonstrated in connection with artists such as Leonardo da Vinci and indeed Freud himself, this does not make it any the less legitimate to go in search of those infantile/unconscious motifs and affective sources powering Elias' prodigious scholarly creativity and informing his work, in however sublimated a form. Proceeding from the observation that successful scholarly or artistic production represents a synthesis of the forces of id, ego and super-ego, i.e. of affect, knowledge and conscience, the author demonstrates that concerns of central moment to Elias' thinking--commitment and non-involvement, establishment and outsider, the restraining of aggression in the civilizational process, interdependence of individuals--are partly the product of early experiences which Elias was able to turn to fruitful account in his work. PMID- 8362079 TI - Microvasculature and radiation damage. PMID- 8362081 TI - Radiopathology of the lung: experimental and clinical observations. PMID- 8362080 TI - Combined chemo-radiotherapy with carboplatin, 5-fluorouracil and folinic acid for cancer of the urinary bladder: acute and late side effects. PMID- 8362082 TI - Diagnosis of radiation-pneumonitis. PMID- 8362083 TI - Lung effects after total body irradiation of mice and bone marrow transplant patients: comparison of experimental and preliminary clinical data. PMID- 8362084 TI - Experimental studies on the pathogenesis of damage in the heart. PMID- 8362085 TI - Myocardial infarction after irradiation in Hodgkin's disease: a review. PMID- 8362086 TI - The time factor for late reactions in radiotherapy: repopulation or intracellular repair? PMID- 8362088 TI - Myelopathy and hyperfractionated accelerated radiotherapy: a radiobiological interpretation. PMID- 8362087 TI - Experimental radiation damage of the central nervous system. PMID- 8362089 TI - Irradiation-induced brain dysfunction in children. PMID- 8362090 TI - Central nervous system injury from implanted isotopes. PMID- 8362091 TI - Long-term cerebral side-effects of total body irradiation and quality of life. PMID- 8362092 TI - Eye sequelae following external irradiation. AB - The early reactions of the eye to radiation are conjunctivitis and, with higher doses, corneal damage. The inflammatory reactions are transient and remit within a few weeks after the end of radiotherapy. Doses above 60 Gy can produce corneal ulcerations with the risk of perforation and loss of the eye. The most frequent late reaction of the eye is cataract of the lens. The tolerance dose (about 5 Gy) is extremely low and the latent period varies from 6 months to 3 years. The lens in children has a much lower tolerance. The increasing potential for optical support and ophthalmic surgery over recent decades has reduced the fear of this complication. The most severe late complications are retinopathy (RR) and neuropathy of the optic nerve (RON), both of which are caused by radiation induced microangiopathy. Visual loss is very frequent and complete blindness is seen with high doses in the range of 50-60 Gy. The latent period of these injuries varies widely from 1 month to 15 years, but they usually occur within 3 years of treatment. Conflicting frequencies are reported in the literature. Beyond 30 Gy, usually no RR is seen. However, the lowest recorded dose producing RR is 11 Gy. In the high dose range of 60-70 Gy RR and RON are found in 10%-100% of patients. There is a great need for prospective trials to estimate the true risk to patients with nasopharyngeal, maxillo-ethmoidal, and orbital tumors, pituitary adenomas, and tumors of the salivary glands. To minimize complications of radiotherapy to the eyes daily fractions should be reduced to 1.7 1.8Gy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362093 TI - Late side effects of pediatric radiotherapy. PMID- 8362094 TI - Side-effects after combination therapy for Ewing's sarcoma. PMID- 8362095 TI - Subclinical impairment of renal function after radiotherapy for Hodgkin's disease in children. PMID- 8362096 TI - Incidence of secondary malignancies in patients with Hodgkin's disease: preliminary results. PMID- 8362097 TI - The response of tissues to very low doses per fraction: a reflection of induced repair? PMID- 8362098 TI - Clinically important factors modifying the response of tumors and normal tissue to radiation therapy. PMID- 8362099 TI - Dose-response relationships for late effects on skin and mucosa. PMID- 8362100 TI - Early and late normal tissue injury after postmastectomy radiotherapy. PMID- 8362101 TI - Muscle injury in experimental intraoperative irradiation. PMID- 8362102 TI - An experimental in vivo model in mice to evaluate the change in reservoir function of the urinary bladder due to irradiation alone or combined with chemotherapy. PMID- 8362103 TI - [Pulmonary tuberculosis and HIV seropositivity at the Principal Hospital of Dakar (Senegal)]. AB - In a prospective survey conducted in 1990 in the Principal Hospital of Dakar, pulmonary tuberculosis was 2.3 times more frequent in HIV seropositive patients (12.5%) than in HIV seronegative patients. We studied 22 cases of pulmonary tuberculosis in HIV+ patients and compared them with a control group of HIV- patients admitted for pulmonary tuberculosis. Tuberculosis occurred in 6 out of 22 asymptomatic HIV+ patients, in 15 out of 22 patients with clinical AIDS and in 1 patient with ARC syndrome. Clinical signs were the same as in controls, except for patients with advanced AIDS who developed cardinal signs. TB intra-dermal reactions were more often negative in HIV+ patients, notably those with HDV1, expressing immunodepression. Radiological images were typical in 81% of patients and in 86% of controls. However, concomitant infections were common in both groups, with atypical radiology and hyperleukocytosis. At light microscopy, there was no difference in the frequency of acid and alcohol fast bacilli between the two groups. The mortality rate was increased in HIV+ patients, but this was not due to tuberculosis. Relapses were frequent in both groups, due to poor compliance with treatment. PMID- 8362104 TI - [Consequences of specific prevention on the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection. Comite SIDA de l'Hopital Saint Antoine]. AB - In a prospective study the authors compared the clinical, radiological, biochemical and diagnostic features of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients who were or were not receiving a specific prophylactic treatment. The study included 386 patients with suspected PCP, 201 of whom were under specific prophylactic therapy. Induced expectoration and/or bronchoalveolar lavage provided a diagnosis of PCP in 89 patients, 21 of whom were under specific prophylaxis. Apart from a number of circulating CD4 lymphocytes that was significantly lower in the patients under prophylaxis, there was no significant difference between the two groups. Thus, being under specific prophylaxis should have no effect on the diagnosis of PCP in HIV-infected patients. PMID- 8362105 TI - [Detection of subjects at risk of type 1 diabetes. GOFEDI. Groupe Ouest-France pour l'Etude du Diabete Insulino-dependant]. AB - The so-called type 1 (insulin-dependent) diabetes is an autoimmune disease occurring in genetically predisposed subjects. The clinical onset of the disease is preceded by a subclinical period during which insulin-producing cells are progressively destroyed by immunological effectors. This prediabetic phase can be detected by the presence of autoantibodies directed against islet cells and sometimes associated with anti-insulin antibodies in children, and later on by the disappearance of the early insulin secretion peak in response to intravenous glucose. It is at this prediabetic phase that immunomodulators specific to the antipancreas process and devoid of side-effects will be used, when available, and that an early insulin therapy will be instituted. PMID- 8362106 TI - [Infection and diabetes]. AB - The susceptibility of diabetic patients to infection is well known, but there is a difference between susceptibility to bacterial and viral infections. Susceptibility to bacterial infections is obvious: septicaemias are more frequent in diabetics than in the non-diabetic population. Its mechanism is the influence of glycaemia on polymorphonuclear cell functions. Some particular clinical entities, such as urinary tract infection, "diabetic foot" or infectious cellulitis, are studied; their bacteriological characteristics may require changes in the first-line antibiotic therapy. It has been demonstrated that hyperglycaemia does not alter the pharmacokinetics of antibiotics. In all cases the role played by normoglycaemia must not be overlooked in the fight against bacteria. The viral infection problem is very different since, apart from autoimmune phenomena, the cellular and humoral responses are not modified in diabetic patients. A few, special mycological infections are also described. PMID- 8362107 TI - [Hematologic manifestations in Campylobacter coli septicemia. Apropos of a case]. AB - We report the case of a 71-year old male patient with a chronic lymphoid leukaemia of 10 years' duration who abruptly suffered deterioration of this general condition and haematological disturbances suggesting worsening of this blood disease (Richter's syndrome). Blood cultures demonstrated a Campylobacter coli septicaemia. Treatment with antibiotics resulted in a return to the previous clinical and biological situation. The various visceral manifestation of the infection are discussed. PMID- 8362108 TI - [Septic Campylobacter fetus thrombophlebitis: a new case]. AB - The diagnosis of septic thrombophlebitis is difficult and often delayed, but it must be borne in mind in all cases of venous thrombosis accompanied by signs of local and/or systemic infection, or deteriorating under heparin therapy. We report a case of septic thrombophlebitis caused by Campylobacter fetus subspecies fetus. The characteristic features, obtained from the literature, of septic thrombophlebitis caused by Campylobacter spp are presented. PMID- 8362109 TI - [Severe hyponatremia disclosing adenohypophyseal insufficiency with empty sella syndrome]. AB - We report a case of extremely severe hyponatraemia which led to the discovery of anterior hypophysis insufficiency associated with empty sella turcica in a dysimmune context. This type of hyponatraemia is consecutive to corticotropic and thyreo-tropic hormones deficiency and to inappropriate secretion of arginine vasopressin. These endocrine abnormalities are of suprapituitary origin. They can be explained by a hypothalamo-hypophyseal dysregulation of little known mechanism, or by a lesion of the hypothalamus. PMID- 8362110 TI - [Alcoholism and severe pneumococcal infection. Apropos of a case of purpura fulminans caused by Streptococcus pneumoniae]. AB - A 43-year old woman presented with lethal purpura fulminans caused by a Streptococcus pneumoniae infection with pneumonia, bacteraemia and meningitis. The only predisposing factor identified was severe chronic alcoholism. The high morbidity and mortality rates of pneumococcal infections in alcoholics are emphasized. PMID- 8362111 TI - [Spontaneous dissection of the anterior interventricular coronary artery in the postpartum period]. AB - We report a case of anterior myocardial infarction which occurred in a young woman without history of cardio-vascular disease 10 days after she had given birth. Coronary arteriography performed 2 months later showed a pseudo-aneurysm of the anterior interventricular artery consecutive to spontaneous dissection of this vessel. The other coronary arteries were normal. PMID- 8362112 TI - [Malignant transformation of leg ulcers]. AB - The authors report a case of malignant transformation (carcinoma cuniculatum) of a venous leg ulcer developed since 60 years. They draw the principal lessons from the review of literature. PMID- 8362113 TI - [Value of ketoconazole in the treatment of Cushing disease]. AB - Ketoconazole has been successfully used in short-term treatment of Cushing's syndrome. We treated 4 patients who had Cushing's disease with ketoconazole administered during 5 to 18 months. Two of them are still controlled after 15 months of treatment and 7 months after treatment was withdrawn. In the other two patients, treatment was ineffective primarily and after 5 months. Our data confirm the usefulness of ketoconazole in the treatment of Cushing's disease, but they also show that primary resistance and tachyphylaxis in long-term treatment may occur, as previously reported. PMID- 8362114 TI - [Hemorrhagic colitis following a treatment with metacycline]. PMID- 8362116 TI - [Cholangiopathies in AIDS]. PMID- 8362115 TI - [Unexpected beneficial effect of the ingestion of zolpidem (Stilnox)]. PMID- 8362117 TI - [Internal medicine: attempt at definition and appeal to a consensus]. PMID- 8362118 TI - [Disorders of the hypothalamo-hypophyseal-ovarian axis in chronic alcoholic women]. AB - This paper deals with the physiology of menstrual cycle disturbances in alcoholic women. Nineteen women, aged from 25 to 45 years, were investigated for the quality of their menstrual cycle (amenorrhoea in 6, spanomenorrhoea in 5, normal cycle in 8) and for their clinical, biochemical and, when possible, histological hepatic status. In all these women, hormone levels were measured (in the early follicular phase for those with normal menses), including E2, E1, LHRH test, T, delta 4A, SBG, T4L, T3L, cortisol and prolactin. According to their hormonal profile, these women were classified as hypothalamo-pituitary amenorrhoea (n = 4), premature menopause (n = 2), ovarian dystrophy (n = 1) and normal hormone levels (n = 12). Although our results are too few for statistic value, it appears that the amount of alcohol consumed, the degree of malnutrition and the hepatic abnormalities observed are more important in women with abnormal hormonal profile. PMID- 8362119 TI - Case for nephron-sparing surgery in managing renal cell carcinoma. PMID- 8362120 TI - Screening for prostate cancer in 1993: is it appropriate, or not? AB - Screening for prostate cancer is a complex problem with scientific, medicolegal, and socioeconomic consequences. Recommendations regarding screening should be based on scientific studies rather than on personal biases. At present, the value of screening is unknown, and hopefully proper studies will provide adequate information in the future. Until then, patients should be educated about the advantages and disadvantages of screening and should participate in the decision. PMID- 8362121 TI - Treatment of pathological stage T3N+M0 bladder cancer: the case for observation. PMID- 8362122 TI - Treatment of high-stage bladder cancer: case for adjunctive chemotherapy. PMID- 8362123 TI - Management of penile carcinoma: the case for selective application of inguinal lymph node dissection in stages T1-T4. PMID- 8362124 TI - The case for inguinal lymph node dissection in the treatment of T2-T4, N0 penile cancer. AB - The battle for the control of squamous cell carcinoma of the penis is either won or lost at the level of the inguinal lymph nodes. Few patients die of distant metastasis without prior development of ilioinguinal nodal disease. If death or recurrence does occur, it does so typically within 2 years. In clinical stage T2 T4, N0 disease, there is a high risk of nodal involvement. In those patients with positive nodes, lymphadenectomy can be curative. It is apparent that forms of therapy other than a surgical approach are distinctly inferior. Awaiting the development of nodal metastasis carries the risk of a significantly lower survival time. Unfortunately, highly sensitive and specific forms of preoperative staging do not exist. With current techniques, ILND can be accomplished with minimal morbidity. For these reasons, it is recommended that all patients with clinical T2-T4, N0 squamous cell carcinoma of the penis undergo immediate inguinal lymphadenectomy. PMID- 8362125 TI - Has the pendulum swung too far for continent diversion? A case for ileal conduit. PMID- 8362126 TI - [Hydration of the patient at the end of life]. PMID- 8362127 TI - [Pathophysiology of dehydration]. AB - The pathophysiology of dehydration is reviewed. The normal response to dehydration, i.e. decreased effective arterial blood volume or effective circulating volume is described. Due to water retention and drinking following stimulation of ADH secretion and thirst, osmoregulation is overruled by volume conservatory mechanisms, which lead to hyponatremia. Only patients with impaired mental function or those who are unable to drink will develop a progressive water deficit--with or without salt depletion--recognizable by hypernatremia. Decreased effective arterial blood volume and hypernatremia affect cerebral function in a way that perception of external stimuli as well as perception of pain will be impaired. Alert dehydrated patients are disturbed mainly by thirst and dryness of the mouth. Both symptoms are perceived more intensely by young than by elderly persons. Dryness of the mouth increase thirst on its own. Distress by thirst and oral dryness increases as a function of the level and the rapidity of developing hypernatremia. The simple act of filling the oral cavity with fluid and swallowing alleviates thirst in the absence of any change in plasma sodium concentration. Thirst quenching efficacy is increased by administering chilled hypotonic fluid with lemon or other fruit acid added (for stimulation of salivation). PMID- 8362129 TI - [Technical aspects of rehydration]. AB - Rehydration of terminally ill patients is from a technical point of view not more difficult than fluid treatment of any other patient. The difficulty lies in the balanced decision between the appropriate method on one hand and the desirability of a rehydration on the other hand. The route of choice in terms of burden for the patient as well as from a logistic point of view is the oral one. If it fails fluid can be administered via transnasal gastric tube. Percutaneous endoscopic gastrostomy and other types of gastrostomy do not provide any advantage over gastric tube for patients with imminent early mortality and those in a hospital. Subcutaneous infusions provide at least for a short time a suitable method for rehydration also and in particular for terminally ill patients. Peripheral venous catheters are suitable for rehydration, however only for a period of few days until another solution is found. PMID- 8362128 TI - [Fluid administration in terminally ill geriatric patients]. AB - Dehydration is common in the elderly. It is caused by a diminished perception of thirst, drugs, and many acute illnesses. Dehydration leads to unspecific signs and symptoms. Proper diagnosis reverses the situation. A restriction of hydration in the sense of palliative terminal care must therefore exclude carefully reversible dehydration and establish clearly that a terminal situation is present. If the careful evaluation of the patient leads to the conclusion that a rapidly progredient worsening of his condition is to be expected, that neither a cure nor a symptomatic improvement are possible and death will occur within days or a few weeks and that the patient would probably consent: a terminal dehydration can be appropriate. PMID- 8362130 TI - [A case from practice (272)--cerebral cysticercosis (neurocysticercosis)- infection with larvae of Taenia solium, swine tapeworm]. PMID- 8362131 TI - Managing organisational stress, Part 2. PMID- 8362132 TI - Citizenship and user-involvement in health provision. PMID- 8362133 TI - Profiling the high-risk altered body image patient. PMID- 8362134 TI - Caring on the outside. PMID- 8362135 TI - Strategy for nursing research. PMID- 8362136 TI - Project 2000 and local staff nurse development. PMID- 8362137 TI - Shared practice in community nursing. PMID- 8362138 TI - Liberal education and the purchaser-provider link. PMID- 8362139 TI - Theory-to-practice links. PMID- 8362140 TI - Perceived value of the ENB framework. PMID- 8362141 TI - Residualism by attrition. PMID- 8362142 TI - Teaching nursing research. PMID- 8362143 TI - Nursing at a managerial crossroads? PMID- 8362144 TI - [The esophagus in Chagas' disease]. PMID- 8362145 TI - [Toxocariasis. A rare disease or rarely recognized?]. PMID- 8362146 TI - [Non-neoplastic polyps of the colon]. AB - Non-neoplastic colon polyps are benign lesions with normal histology components, we present our experience with colonoscopy polypectomy in 10 years. We resected 187 polyps in 96 patients (50 males) with medium age of 49.3 years and range 2 82. Most common indication was hemorrhage (37%) taking out the hyperplastic polyps who were found in asymptomatic patients with the highest frequency (41%). Juvenile polyps follows with 25%. 71% polyps were unique but hamaetomatous polyps of Peutz-Jeghers syndrome were multiple (39%). Juvenile (retention) polyps were found among the youngest patients (average 13.2 years) and frequently had hemorrhage (21-25). Lipomas were found in elder patients (range 52.5 years). We had no major complications with hemorrhage or mortality, minor complications were found in 3.09%. PMID- 8362147 TI - [The in-vitro digestive availability of lipase and trypsin in pancreatic supplements under different degrees of acidity]. AB - We evaluated the in vitro disintegration time and the remanent digestive activity of eight pancreatic supplements under pH conditions similar to the gastrointestinal tract. They were incubated for 45 min at various pH levels (1, 3 or 6) and continued thereafter at pH 6, for another 135 min. The activities of lipase and trypsin were evaluated titrimetrically every 15 min. At pH 6, the products without an enteric coat and Creon, showed the shortest disintegration times; under acidic conditions, those times were longer in all the enteric coated products. At constant pH 6, lipase activity was greater in Creon, Pankreon and Cotazym-B; trypsin activity was greater in Nutrizym-C, Onoton and Cotazym-B. After acidic pH exposure enzyme bioavailability was decreased in all the products. Disintegration times and acid inactivation of enzymes, should be considered when prescribing PS. PMID- 8362148 TI - [Mirizzi's syndrome: a rare cause of obstructive jaundice]. AB - We present five patients with Mirizzi syndrome diagnosed by ERCP. This syndrome is a rare cause of obstructive jaundice due to common biliary duct compression by a gallstone impacted in the cystic duct, neck of the gallbladder or Hartmann's pouch. Complications are bilio-biliary fistula, cholangitis and secondary biliary cirrhosis. Diagnostic methods, importance of preoperative diagnosis and surgical technics are reviewed. PMID- 8362149 TI - [Hemangioma of the rectosigmoid. A report of a case treated by conservative surgery of the sphincters]. PMID- 8362150 TI - [Toxocara canis associated with splenic rupture]. PMID- 8362152 TI - CDT today: why does it take so long for candidates to get test results? PMID- 8362151 TI - [Chagasic megaesophagus with positive serology and xenodiagnosis]. PMID- 8362153 TI - Denture esthetics: festooning the complete denture. PMID- 8362154 TI - Improved method to secure Harder clips. PMID- 8362155 TI - Final OSHA standard on occupational exposure to bloodborne pathogens. PMID- 8362156 TI - Procedures for fabricating precision-fitting bridge castings: a consistently accurate approach. PMID- 8362157 TI - Crown and bridge/implant waxing and spruing step list. PMID- 8362158 TI - Solving set up problems. PMID- 8362159 TI - Technician-dentist communication: the key to superior restorations. PMID- 8362160 TI - Fabrication of custom milled attachments with screw fixation. PMID- 8362161 TI - Mastering the dental surveyor: an instrument for the whole laboratory. PMID- 8362162 TI - "Dental Technology 2000" conference and "Building Legislative Coalitions" NADL's 1993 legislative conference. PMID- 8362163 TI - In the public interest. PMID- 8362164 TI - Inside the dental laboratory: management's perspective of remakes and communication. PMID- 8362165 TI - ADA legislative activity: who fights the battles and how? PMID- 8362166 TI - Getting a piece of the action. PMID- 8362167 TI - Crown lengthening: what is it? Who needs it? PMID- 8362168 TI - The role of CT in functional endoscopic sinus surgery. AB - The intricate anatomy of the paranasal sinus unit (sinus/nasal cavities and ostia) and its relations to the orbit and anterior cranial fossa make accurate pre-operative evaluation of disease in this region mandatory before undertaking functional endoscopic sinus surgery (FESS). Plain radiography often fails to provide vital information in cases of chronic rhinosinusitis, especially of the ethmoid labyrinth, which is a key area of the paranasal sinus unit. Computerized tomography has significantly enhanced the scope of endoscopic sinus surgery by offering the surgeon hitherto inaccessible information regarding the sinus status. In this article, we review the pros and cons of the two imaging modalities, and present our experience fo 70 CT scans in patients of FESS. We also propose a surgical classification of CT findings. All in all, plain radiographs prove to be of little value for pre-operative assessment in FESS, while CT scans are an essential tool. PMID- 8362169 TI - Nasal hyperreactivity. A histamine provocation model. AB - The aim of the study was to see whether it is possible to select non-allergic persons with hyperreactivity, especially in the nose, from healthy individuals with a histamine standardization test. Another aim was to elucidate whether a so called priming effect could be present in such a non-allergic disorder. Seven patients with a history of perennial rhinitis, expressed as either or both swelling or discharge from the nose and a negative allergic investigation, were examined on three up to seven consecutive occasions. Rhinostereometry was used to register the reaction in the mucous membrane to a solution of histamine in successively increased concentrations. The results showed a statistically significant difference between this group compared with a control group of healthy volunteers. We could not detect any increase in the sensitivity during repeated provocations. PMID- 8362170 TI - The role of acoustic rhinometry in studying the nasal cycle. AB - The nasal cycle has been demonstrated in man using several techniques, including magnetic resonance imaging, anterior rhinoscopy, rhinomanometry, all of which have limitations due to expense, discomfort, limited scope or poor reproducibility. Acoustic rhinometry is a new technique which analyses nasal geometry throughout the nasal cavity, not just at the flow-limiting segment. Six adult volunteers were examined at 15-to 30-min intervals using acoustic rhinometry. The classical alternating cycle was seen in three subjects, a non classical cycle was seen in two, and no cycle seen in one subject. Changes occurred throughout the nasal cavity and corresponded with fluctuations in subjective scores of obstruction and, in one case, with nasal resistance measurements. Acoustic rhinometry is a rapid, reproducible and non-invasive technique. This pilot study demonstrates that it has potential for studying in detail the physiology of the nasal cycle. PMID- 8362171 TI - Continuous infrared thermometry of the nasal mucosa. AB - This study aims to continuously measure nasal mucosal temperature without interruption of nasal breathing using infrared thermometry. An infrared thermometer (Medi-Therm 310; Everest Interscience, Inc.) was directed at the nasal septum from a distance of 15 cm. Infrared radiation was continuously collected, then converted to an electrical signal proportional to the mucosal temperature and output to a chart recorder. In 70 subjects the mean nasal mucosal temperature was 30.4 +/- 2.0 degrees C on inspiration and 32.0 +/- 1.8 degrees C on expiration. Using multiple regression, nasal mucosal temperature was significantly related to atmospheric temperature (p < 0.0001) and inversely related to the airway patency of the ipsilateral nasal passage (p < 0.05). PMID- 8362172 TI - Repair of saddle nose deformity in Wegener's granulomatosis and ectodermal dysplasia. AB - Two cases are reported involving surgical treatment of a saddle nose deformity due to Wegener's granulomatosis and ectodermal dysplasia, respectively. The association of ozena with both diseases requires special consideration for any type of transplants because of a high risk of infectious complications. By extranasal incisions the nasal dorsum has been successfully reconstructed by transplanting autogenic conchal cartilage. There has been no resorption or displacement of the transplant after twelve months in the case of ectodermal dysplasia, and after 25 months in the patient with Wegener's granulomatosis despite a severe recurrence of this disease. PMID- 8362173 TI - Transnasal electrocoagulation of the vidian nerve. AB - Vidian neurectomy has previously been reported as having a high success rate in alleviating secreto-motor rhinopathies. We report a prospective study of 24 consecutive patients who underwent transnasal vidian electrocoagulation. An overall improvement in symptoms was found in 59.1%. A worsening of overall nasal symptoms was complained of by 27.3%. The possible reasons for this are discussed. PMID- 8362174 TI - The effect of methacholine on nasal transmucosal potential difference in normal human subjects. AB - This study was proposed to test the hypothesis that the parasympathetic system might attribute to the transmucosal potential difference. In a double-blind, placebo-controlled study six volunteers had nasal transmucosal potential difference (NTPD) recorded at 4-min intervals during 12-min periods of rest, before and after treatment, as well as during exercise and recovery. Application of placebo did not significantly alter NTPD at rest. There was a significant rise during exercise (p < 0.05). The application of methacholine significantly increased NTPD at rest (p < 0.01); there was a further rise during exercise (p < 0.02). We conclude that parasympathetic stimulation can increase the transmucosal potential difference. PMID- 8362175 TI - A preliminary comparison of the effects of halothane and isoflurane on nasal mucosal blood flow. AB - The differing effects of halothane and isoflurane on nasal mucosal blood-flow was investigated by means of laser-doppler flowmetry in a total of fourteen patients who received one of these inhalational agents during anaesthesia. A trend towards lower nasal flux was seen in the halothane group but, due to insufficient numbers, significance could not be demonstrated. These changes in flux appeared not to be related to the falls in perfusion pressure which were seen in both groups of patients and were thought to be due to locally vasoactive effects. PMID- 8362176 TI - Blindness after intranasal ethmoidectomy. AB - Orbital haemorrhage is an unusual and frustrating complication of ethmoid surgery. A case of reversible blindness which was due to intra-operative orbital haemorrhage occurring after intranasal ethmoidectomy is presented. Prevention and management of this kind of blindness can be reversed, if treated aggressively. PMID- 8362177 TI - Nasal dorsal cyst after rhinoplasty. AB - Nasal dorsal cyst formation after rhinoplasty is considered a rare complication. These cysts are due to entrapment of mucosal remnants in the subcutaneous space. Meticulous surgical technique aimed at preserving the mucosal lining may prevent cyst formation. Surgical excision with the open approach is a reliable treatment. A case of nasal dorsal cyst after previous rhinoplasty is presented. After four years no sign of recurrence is noted. PMID- 8362178 TI - Perennial non-allergic rhinitis (NAR) is a chronic nonpurulent disease. PMID- 8362179 TI - Time to give up an ineffective method of assessing fractures. PMID- 8362180 TI - It takes awareness and vigilance to stop lead poisoning. PMID- 8362181 TI - Not everyone listed in this data bank made a serious error. PMID- 8362182 TI - Innovations in practice. Yes, nursing care is cost-effective. PMID- 8362183 TI - Beyond QA, the easy way. PMID- 8362184 TI - Cutting postop pain. PMID- 8362185 TI - Von Hippel-Lindau: a relentless disorder. PMID- 8362186 TI - A nurse fights the system--and wins. PMID- 8362187 TI - OTC interactions. Antacids. PMID- 8362189 TI - Deciphering the new food labels. PMID- 8362190 TI - You be the judge. PMID- 8362188 TI - Catheterization: how far should you go? PMID- 8362191 TI - Phantom breast pain following mastectomy. PMID- 8362192 TI - Bedpans and blood--changing perceptions about nursing. PMID- 8362193 TI - This RN had a close call with RSDS. PMID- 8362194 TI - What about the rash that signals Lyme disease? PMID- 8362195 TI - Effects of oral rinsing with triclosan and sodium lauryl sulfate on dental plaque formation: a pilot study. AB - Mouthwashes containing 0.3% or 0.15% triclosan in combination with 1.5% sodium lauryl sulfate (SLS) produced a significant reduction in plaque formation in a test panel of 11 students who refrained from oral hygiene during the test periods, during which they rinsed twice daily with different mouthwashes. Pl.I. was evaluated after each test period. A mouthwash containing only 1.5% SLS inhibited plaque to almost the same degree. In both cases, the major effect was on the buccal/lingual surfaces, where score 2 was changed to score 0. Addition of triclosan appeared to reduce the untoward side-effects of mouth-washes containing SLS alone (i.e. desquamation and a burning sensation in the mouth). PMID- 8362196 TI - Specific antibodies against Actinobacillus actinomycetemcomitans in serum and saliva of patients with advanced periodontitis. AB - The aim of the present study was to discover any possible correlation between specific antibodies against Actinobacillus actinomycetemcomitans (A.a.) in serum and saliva. The test group consisted of 38 patients aged 31-68 yr (mean 49) with advanced periodontitis. Twenty-nine subjects aged 23-67 yr, without periodontal destruction, formed a control group with a reference level of specific salivary antibodies against A.a. A subgingival plaque sample for culturing A.a., a specimen of stimulated whole saliva, and a sample of venous blood were taken from each subject of the test group. Specific IgG and IgA antibodies against A.a. were determined from serum and stimulated whole saliva by means of the ELISA test. Fifteen of the patients (39%) had cultivable A.a. Six of the 15 A.a. culture positive patients and one of the 29 reference subjects exhibited very high antibody titers against A.a. in saliva. Specific IgG and IgA antibodies in saliva correlated highly significantly with the corresponding antibody values in serum among the patients in the test group. It was concluded that among patients with severe adult periodontitis, the less invasive saliva sample has a diagnostic value equal to that of the serum sample concerning specific antibodies against A.a. PMID- 8362197 TI - Effect on human teeth of renal transplantation: a postmortem study. AB - Extracted teeth from five deceased patients treated by renal transplantation were examined radiographically and histologically, and compared with teeth from healthy persons of approximately the same age. In three of the patients with a renal transplant, the radiographs showed normal pulp chamber sizes, but histologic examination revealed a widened predentin zone, approximately four times greater than in the controls. In two of the patients the radiographs showed marked reduction of the pulp chamber size. The histologic changes of these teeth were mainly an extensive amount of secondary dentin along the pulp chamber walls and the root canals, with a markedly reduced pulp space. One explanation for the difference between the patients was that patients with extensive pulp calcifications were given a higher total amount of corticosteroids than patients with a widened predentin zone. PMID- 8362198 TI - A modified device for collection and flow-rate measurement of submandibular sublingual saliva. AB - The aims of the present study were to measure stimulated submandibular-sublingual (SM-SL) salivary flow rate with a modified Block-Brottman collection device, and, further, to evaluate the reliability of measurements of stimulated SM-SL salivary flow rate by means of this modified Block-Brottman device, as compared to measurements of parotid flow rate using modified Carlson-Crittenden cups. Twenty nine healthy female volunteers, aged 36 +/- 7 yr, were included. Saliva stimulation was achieved by application of a 3% citric acid solution to the rims of the tongue four times/min, for 3 s every 15 s. On 3 consecutive days, stimulated parotid and SM-SL salivas were collected for 2 min at 07.30, before breakfast (morning value), and at 10.00, 2 h after a standard breakfast (lunchtime values). SM-SL saliva was also collected on one occasion for 2 min x 3. For parotid and SM-SL saliva, the mean stimulated flow rates were in the morning, 1.50 +/- 0.83 and 2.25 +/- 1.12 ml/min, and at lunchtime, 1.71 +/- 1.16 and 2.54 +/- 1.01 ml/min, respectively. For both salivas, lunchtime values were significantly higher than morning values by about 13-14%. Comparing parotid and SM-SL saliva flow rates, we found the SM-SL saliva flow rate to exceed the parotid flow rate by about 50% both in the morning and at lunchtime. Variations in flow rate were analyzed by means of ANOVA. Interindividual variance and variance between measurement days and times of day made up 88% of parotid and 83% of SM-SL total variance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362199 TI - Protein composition, adhesion, and agglutination properties of saliva in burning mouth syndrome. AB - Resting and stimulated whole saliva and parotid saliva of men and pre- and post menopausal women with burning mouth syndrome (BMS) and their matched controls were studied. Women with BMS had slightly, but not significantly, higher flow rates than their controls. The total protein concentration in stimulated saliva of women with BMS was significantly lower than that of controls. This difference was not associated with the flow rate. The proportional amount of sialic acid, used as an indicator of mucin concentration, was higher in subjects with BMS than in their controls. SDS-PAGE showed no consistent differences in the protein profiles of saliva, nor were any differences observed in the adhesion or agglutination assays between subjects with BMS and their matched controls. Thus, the present results indicate that BMS is not associated with a decrease in the protecting and lubricating properties of saliva. PMID- 8362200 TI - Cortical bone mineral density in the mandible and osteoporosis status in postmenopausal women. AB - Mineral density of the cortical bone of the mandible was determined by single energy QCT (quantitative computed tomography) for 77 menopausal women. Bone mineral densities (BMD) were measured in the buccal and lingual layers of the cortex, distally from the foramen mentale, on both sides of the mandible. All the women were edentulous in that region, and the alveolar processes were far resorbed. These results were compared with the BMD values of the femoral neck, lumbar spine, and trabecular portion of the mandible between the detected layers of cortex. The BMD of the buccal cortex correlated remarkably well with all values, except those of the trabecular portion. Of the women tested, the correlations were lowest in the least osteoporotic group. The values for the lingual cortex did not correlate with other variables as well as did those for the buccal cortex, but in the most osteoporotic part of the sample the lingual cortex values correlated significantly with the BMD of the trabecular portion. The BMD values for the buccal cortex were significantly higher than those for the lingual cortex. PMID- 8362201 TI - Effect of subperiosteally implanted polytetrafluoroethylene (PTFE) material on alveolar bone in the rat. AB - The aim of this study was to examine the effect on osteocytes after subperiosteal implantation of polytetrafluoroethylene (PTFE) material in the rat maxilla. In four young conventional albino rats, mucoperiosteal flaps were elevated by sulcular incision, and segments (1 x 4 mm) of PTFE material were implanted between bone and flap tissue. After a healing period of 14 days, specimens containing implants and adjacent bone were processed for transmission electron microscopy. The specimens were stepwise reduced to obtain a total of 16 levels for thin sectioning. Osteocytes (n = 640) in alveolar bone underlying implanted material (region 1) and adjacent bone (region 2) were studied to determine the ratio of intact to degenerated cells. In alveolar bone covered by implanted material (region 1) and adjacent bone (region 2), 56% and 16% of the osteocytes, respectively, showed distinct signs of necrocytosis. This study has shown that subperiosteal placement of PTFE material results in partial necrosis of superficial alveolar bone. PMID- 8362202 TI - Cytotoxic and antibacterial effects of orthodontic appliances. AB - The cytotoxic and antibacterial effects of orthodontic appliances were assessed. Metallic devices used in orthodontics, such as molar bands, brackets, and archwires were tested by the agar overlay cytotoxicity test with mouse fibroblast cells. The same devices were tested for antibacterial effect with Streptococcus mutans and S. sanguis. The multicomponent devices, which are bonded with silver- and copper-based brazing alloys, were more cytotoxic than the single-component devices, probably because copper is more cytotoxic than nickel. The devices had a definite, but low, antibacterial effect, as compared with the 0.05% chlorhexidine positive control. A cytotoxic effect of the devices per se might contribute to a localized gingivitis. It is uncertain whether orthodontic devices have any significant inhibitory effect on dental plaque viability. PMID- 8362203 TI - Clinical study of oral galvanism: no evidence of toxic mercury exposure but anxiety disorder an important background factor. AB - A total of 142 women and 76 men with self-diagnosed oral galvanism who were referred from dentists and medical doctors for clinical evaluation during the last 2 yr are described from the perspective of general medicine. No case of clinically suspected mercury intoxication was found. Mean concentration of mercury in whole blood (B-Hg) was 17.3 nmol/l, and no value exceeded 50 nmol/l. Amalgam burden and B-Hg were not associated with clinical signs or symptoms except for a significantly lower mean value of B-Hg in patients with psychologic main symptoms than in those without (mean 15.4 vs. 18.1 nmol/l). It was possible to make one or several diagnoses in all 218 cases as reasonable alternatives to the concept of oral galvanism. Mental disorder was the main diagnosis in 93 cases (42.7%), including 41 cases of generalized anxiety disorder and 12 cases of panic disorder. A total of 87 patients (40%) did not work because of medical reasons or unemployment. Amalgam removal was recommended in a total of 65 cases (29%), mainly on psychologic indications, but in 22 cases because of oral conditions. The clinical conditions behind the concept of oral galvanism seem to be explicable in terms of general medicine, and no generalized toxic effect of amalgam fillings need be suspected. PMID- 8362204 TI - Nordic dentists' opinions on the safety of amalgam and other dental restorative materials. AB - The safety of amalgam and other restorative materials has caused concern among dental patients in recent years. The aim of this study was to obtain information on dentists' perceived competence in handling different filling materials and their opinions on the safety of these. A random sample of practising dentists in Denmark, Finland, Norway, and Sweden received a mail questionnaire in spring 1990. Answers were received from 1732 dentists (65%). The study showed that the respondents believed that their theoretic knowledge and clinical skills were generally at a high level regarding restorative materials. The risks of the side effects of gold, ceramic materials, and glass ionomer were considered to be low by about 90% of the respondents. Amalgam was considered to be significantly more hazardous by the Swedish respondents than the others. Interestingly, composite was considered to be associated with a high risk of side-effects by about half of the dentists in all Nordic countries. The dentists' opinions were not found to be greatly influenced by their sex, age, or place of residence but rather by their country and service sector. Against the background of the present lack of scientific evidence on the hazardousness of amalgam or other restorative materials for patients' general health, these findings indicate that dentists are influenced by discussions in the mass media about dental treatment and materials and, of course, by the guidelines given by the health authorities in their own countries. Few dentists were shown to be concerned about occupational risks associated with the use of amalgam, and they had not had their own amalgam fillings replaced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362205 TI - Evaluation of three silicoating methods for resin-bonded prostheses. AB - Three different methods of increasing the bond strength of resin to metal were tested: the original Silicoater technique, the Silicoater MD technique, and the Rocatec system. Metals used for the resin-bonded prostheses were gold, a cobalt chromium (Co-Cr) alloy, and titanium. Silicoating increased the bond strength to sandblasted specimens. The original Silicoater technique produced the highest bond strengths, especially when used with the Co-Cr alloy and titanium. The Silicoater MD technique showed the lowest bond strengths for all of the test metals. Storage for 7 days with protective film on the silicoated surface did not affect the bond strength, as compared with specimens bonded immediately. The retention of the resin to the gold specimens (Rocatec system) decreased after thermocycling, but retention to the Co-Cr alloy and titanium was not affected. Various resin cements were tested and showed the same retention with the exception of Microfill Pontic, which gave a weaker bond. Scanning electron microscope (SEM) and energy-dispersive X-ray analysis (EDAX) of the specimens before and after the measurements gave no clear explanation of the differences in bond strengths between the test metals. However, it was concluded that silicoating of the metal surfaces contributed to the retention of the resin by chemical action, as no differences in adaptation of the resin to the metal were seen between specimens pretreated by sandblasting and those which were also silicoated. PMID- 8362206 TI - Crown retention and cyclic loading (in vitro). AB - Cast gold crowns were luted on extracted and prepared human teeth with zinc phosphate cement and subjected to a fatigue test by cyclic loading. The correlation between crown retention and three retention variables was determined by the fatigue test. The results show that the smallest convergence angle tested, 20 degrees, gave better retention than did angles of 40 degrees and 60 degrees, and that surface roughness, surface size, height, and base diameter of the preparations had no influence on crown retention within the parameter sizes tested. PMID- 8362207 TI - Helicobacter pylori infection in peptic ulcer disease. PMID- 8362208 TI - Intestinal permeability and function in patients infected with human immunodeficiency virus. A comparison with coeliac disease. AB - The relationships among intestinal permeability, advancing human immunodeficiency virus (HIV) infection, and the presence of diarrhoea or weight loss were investigated in 51 HIV patients and 20 healthy controls. Ten patients with untreated coeliac disease were also investigated for comparison. Fasting subjects drank an isosmolar test solution containing D-xylose, lactulose (LL), L-rhamnose (R) and 3-O-methyl-D-glucose. Urine was collected for 5 h, test sugar content being subsequently measured by thin-layer chromatography for the dosing sugars. Intestinal permeability (LL/R excretion ratio) and recovery of D-xylose and 3-O methyl-D-glucose in urine were abnormal in patients with HIV disease, and especially those with diarrhoea, as they were in coeliac disease. Patients with coeliac disease and HIV disease, especially when diarrhoea and/or weight loss were present, had significantly reduced 5-h excretion of L-rhamnose, D-xylose, and 3-O-methyl-D-glucose. These data indicate that abnormal permeability and reduced intestinal absorption capacity are common in HIV patients, occur at all stages of HIV disease, especially in the presence of diarrhoea, and, with the exception of lactulose permeation, are relatively similar to the alterations seen in coeliac disease. PMID- 8362209 TI - Functional gastrointestinal disorders in unselected patients with non-cardiac chest pain. AB - Patients with non-cardiac chest pain (NCCP) (n = 387) and cardiac chest pain (CCP) (n = 93) were compared with community controls (n = 81), using a symptom questionnaire that assessed the presence of irritable bowel syndrome (IBS), functional dyspepsia, and oesophageal dysfunction and chest pain characteristics. A significantly (p < 0.05) increased prevalence of symptoms compatible with IBS occurred in NCCP patients when compared with those with CCP and with controls. Dysphagia was more frequent in both those with non-cardiac and cardiac chest pain than in controls; this was not apparent, however, when patients with concomitant IBS were excluded. The presence of oesophageal or gastrointestinal symptoms did not enable discrimination with regard to the chest pain characteristics. We conclude that unselected referred patients with documented NCCP are more likely to have IBS and that the presence of oesophageal symptoms such as dysphagia may merely reflect the spectrum of the 'irritable gut'. PMID- 8362210 TI - Myofibroblast-like cells produce mRNA for type I and III procollagens in chronic active hepatitis. AB - In chronic active hepatitis the rate of collagen biosynthesis is largely determined by intracellular mRNA concentrations. To localize procollagen mRNA producing cells, we investigated biopsy specimens from five patients with hepatitis B surface antigen-positive chronic active hepatitis and five patients without liver disease by in situ hybridization. We used type I and III procollagen cDNAs for transcription to (35S)-labeled probes. Parallel sections were stained with anti-actin monoclonal antibodies. Our results show that cells in which collagen synthesis is ostensibly enhanced can be localized by in situ hybridization of procollagen mRNAs. These cells were also anti-actin-positive in parallel sections and were localized in areas of inflammatory cell infiltration and necrosis. We conclude that myofibroblast-like cells may express procollagen mRNAs in chronic active hepatitis. Moreover, in situ hybridization may be a valuable diagnostic tool for providing additional morphologic information on the degree of fibrogenesis activity. PMID- 8362211 TI - Follow-up of patients positive in reticulin and gliadin antibody tests with normal small-bowel biopsy findings. AB - Twenty-five patients with positive serum reticulin or gliadin antibody titres and having normal small-bowel mucosal villous architecture were re-biopsied after a follow-up period of 1 to 7 years. Seven were found on control examination to have small-bowel villous atrophy. At the initial examination, when coeliac disease was 'excluded', they thus belonged to the entity latent coeliac disease. Morphometrically minor mucosal changes in the initial biopsy specimen, suggesting an ongoing process, were seen in only three of them. Especially the serum IgA class reticulin antibody test was a good predictor of latent coeliac disease. This study implies that patients with so-called false-positive IgA-class reticulin or gliadin antibody test should be re-examined. PMID- 8362212 TI - Expression of glycoconjugates in pancreatic, gastric, and colonic tissue by Bauhinia purpurea, Vicia villosa, and peanut lectins. AB - We have earlier prepared a pancreatic cancer-associated mucin, whose altered carbohydrate structure was recognized by Vicia villosa (VVA), Bauhinia purpurea (BPA), and peanut (PNA) lectins and which was found preferentially in the sera of patients with pancreatic or gastric cancer. Cancer-associated structures of the sugar chain on serum antigen may reflect those occurring in malignant tissues. Accordingly, we investigated the tissue distribution of carbohydrate structures reactive to these lectins by using lectin histochemistry in pancreatic cancer, gastric cancer, and colonic cancer tissue specimens and in their normal counterparts. VVA showed a higher affinity for pancreatic cancer (77.5%), gastric cancer (89%), and colonic cancer (87%) cells than for the cells of their normal counterparts, whose affinity was 0%, 41.7%, and 36.4%, respectively. PNA showed a higher affinity for pancreatic (70%) and colonic cancer cells (86.5%). BPA failed to show significant binding differences between neoplastic and normal cells in any of the pancreatic, gastric, or colonic tissue specimens. It did, however, bind to intraductal contents in most of the pancreatic cancer tissues but bound to intraductal contents in only a few chronic pancreatitis and normal pancreatic tissues. VVA and PNA did not bind to intraductal contents in any of the normal, chronic pancreatitis, or pancreatic cancer tissues. These results imply that, among the lectins used so far, VVA has the highest affinity for neoplastic cells, and it may provide a supplement for use in the pathologic diagnosis of malignant diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362213 TI - Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis. AB - Serum selenium, copper, and zinc levels were studied in 47 patients with Crohn's disease, 117 patients with ulcerative colitis, and 123 age- and sex-matched healthy controls. Serum selenium levels were lower and serum copper levels were higher in men and women with Crohn's disease than in controls (p < 0.001 and p < 0.01, respectively). Trace element levels were not significantly influenced by extent or localization of Crohn's disease. Men and women with ulcerative colitis had higher levels of copper and zinc than did controls (p < 0.01 and p < 0.05, respectively). Men with pancolitis had significantly lower selenium and higher copper levels than men with proctitis. The implications of abnormal trace element status in patients with inflammatory bowel disease are discussed. PMID- 8362214 TI - Changes in gastric mucosal ornithine decarboxylase and tyrosine phosphorylation of proteins in postgastrectomy patients. AB - There is evidence to suggest that partial gastrectomy is associated with an increased risk of developing gastric carcinoma in humans. Since ornithine decarboxylase (ODC) and tyrosine phosphorylation of proteins are involved in the regulation of cell proliferation, the present study was undertaken to examine the time-dependent changes of these variables in the postgastrectomy stomach. Thirty seven postgastrectomy patients (Billroth I (BI), n = 7, and Billroth II (BII), n = 30) underwent gastroscopy. For comparison, five patients with intact stomachs (three healthy and two postvagotomy and pyloroplasty) were also studied. Gastric mucosal biopsy specimens were obtained within 5 cm of the anastomosis and analyzed for ODC activity. In addition, tyrosine phosphorylation of membrane proteins was also determined in representative samples of BII patients. Gastric mucosal ODC activity was significantly higher in BII patients in whom gastrectomy had been performed > 15 years earlier compared with those in whom it had been performed < 15 years earlier (p < 0.001) or controls (p = 0.004). Although the mean ODC activity was higher in BII than in BI patients, the difference was not significant (p = 0.103). Isolated patients with high ODC activity demonstrated increased phosphorylation of tyrosine membrane proteins with M(r) of 55-60. PMID- 8362215 TI - Chemical nature and distribution of calcium compounds in radiolucent gallstones. AB - A high failure rate for radiolucent cholesterol gallstones to dissolve with oral bile acids may be due to the presence of insoluble calcium compounds. Twenty sets of radiolucent gallstones, 7-20 mm in diameter, obtained from 20 patients undergoing cholecystectomy, were cut, and the outer surface, outer rim, middle portion, and central core areas were scanned for calcium by energy-dispersive X ray microanalysis (EDX) and scanning electron microscopy (SEM). Scrapings from the four areas of each stone were analysed by infrared spectroscopy. A sample of the crushed stone was used for chemical estimation of cholesterol. Eleven (55%) of the 20 cholesterol (84-96% dry weight of cholesterol) stones showed presence of calcium by EDX; the distribution was peripheral in 5, homogeneous in 4, and central in 2. The chemical compound was calcium bilirubinate in 10 and calcium carbonate in 8 stones. Calcium compounds are present in a high proportion of radiolucent gallstones considered suitable for chemodissolution by conventional criteria. Their unrecognized presence may explain the high failure rate of such stones to respond to medical therapy. PMID- 8362216 TI - Effect of short- and long-term treatment with omeprazole on cell cycle distribution in the gastric mucosa. Results of a flow cytometric study. AB - Omeprazole may exert an effect on gastric mucosal proliferation by inhibiting gastric acid secretion and increasing serum gastrin levels. It may also influence the kinetics of endocrine cells and the oxyntic mucosa. The aim of the present study was to evaluate the cell cycle in different gastric compartments following short- (1 month) and long-term (6 months) administration of two different dosages of omeprazole by means of a flow cytometric method. We also determined serum gastrin levels at the same time. No differences in cell cycle distribution of the antrum, body, and fundus were found in the two different dosage groups after 1 month of therapy, considering the synthetic phase (S-phase) of the cell cycle. A statistically significant increase in S-phase was reported after long-term therapy in the mucosa of the fundus and body of the stomach in both groups. Gastrin levels showed no clear correlation with cell cycle distribution variables. We postulate a proliferative adaptation of the oxyntic mucosa to long term drug administration not mediated by gastrin influence. PMID- 8362217 TI - Secretin and portal blood flow. AB - Using a duplex Doppler technique, we investigated the effect of low doses of secretin on the portal blood flow. In eight healthy volunteers successive intravenous secretin infusions of 0, 8, and 32 pmol x kg-1 x h-1 resulted in proportional increases in plasma secretin levels. The portal venous flow, however, was unaffected. A bolus injection of 930 pmol of secretin caused plasma secretin levels to increase 100-fold, whereas blood flow in the portal vein increased only by a factor three. This suggests that secretin in the present dose range is of no quantitative importance as a regulator of portal venous flow under physiologic conditions. PMID- 8362218 TI - Pituitary adenylate cyclase-activating peptide is a potent modulator of human colonic motility. AB - Pituitary adenylate cyclase-activating peptide (PACAP) represents a novel brain gut peptide with high sequence homology to vasoactive intestinal polypeptide (VIP). Since PACAP has been identified in the human gut, the effect of the two molecular forms PACAP-(1-38) and PACAP-(1-27), the hybrid PACAP-(1-23)VIP-(24 28), and VIP on the contractility of the longitudinal muscle of human sigmoid colon was tested in vitro. All peptides inhibited the spontaneous phasic contractions and relaxed concentration-dependently carbachol-precontracted preparations. The effects of the peptides remained unaffected by tetrodotoxin, by inhibition of phosphodiesterase activity, and by inhibition of nitric oxide synthesis. Apamin reduced only the effects of the PACAP peptides, whereas tetraethylammonium blocked only the effect of VIP. In conclusion, PACAP peptides and VIP mediate their relaxant effects via activation of specific PACAP and VIP receptors coupled to different potassium channels. PMID- 8362219 TI - Gastric acid secretion, serum pepsinogen I, and serum gastrin in Japanese with gastric hyperplastic polyps or polypoid-type early gastric carcinoma. AB - We determined the maximum secretion of gastric acid and the fasting serum levels of pepsinogen I and gastrin in Japanese patients with gastric hyperplastic polyps or polypoid-type early gastric carcinoma, comparing those findings with observations in control subjects. Both the maximum acid secretion and fasting levels of serum pepsinogen I were significantly lower in the patients with gastric hyperplastic polyps or polypoid-type early gastric carcinoma than in the controls. Fasting serum gastrin levels were significantly higher in the patients with gastric hyperplastic polyps than in the other two groups of subjects. These data demonstrated that the combination of hypochlorhydria, a low level of pepsinogen I, and hypergastrinemia (type-A gastritis) was common in the patients with gastric hyperplastic polyps, whereas hypochlorhydria and a low pepsinogen I without hypergastrinemia (type-B gastritis) were common in those with polypoid type early gastric carcinoma. PMID- 8362220 TI - Autonomic vagal nerve dysfunction in patients with ulcerative colitis. AB - Autonomic nerve function was evaluated in 40 patients with total ulcerative colitis and in 25 patients with irritable bowel syndrome by three established non invasive tests based on the heart reactions to deep breathing (E/I ratio) and tilt (acceleration and brake index). None of the patients were diabetic. Most of the patients with ulcerative colitis were clinically and biochemically inactive; 10 had previously undergone colectomy. The results were compared with a control group consisting of 56 healthy individuals and 33 previously investigated patients with Crohn's disease, 45% of whom demonstrated autonomic neuropathy (AN). Patients with ulcerative colitis had a significantly lower E/I ratio than controls in age-corrected values, indicating vagal nerve dysfunction. Altogether, 35% had signs of AN. In patients with irritable bowel syndrome 36% had evidence of AN, a figure in agreement with observations from other investigators. We conclude that AN is common in patients with ulcerative colitis, regardless of disease activity and previous colectomy. In contrast to a predominantly sympathetic dysfunction in Crohn's disease, AN in ulcerative colitis was vagal. PMID- 8362221 TI - Propranolol absorption in peptic ulcer disease. AB - This study was designed to determine whether gastroduodenal ulcer influences propranolol absorption. Eleven patients with peptic ulcer disease and eight healthy subjects received 80 mg of propranolol orally. Serum propranolol levels were measured with high-performance liquid chromatography. Ulcer patients showed a significant decrease in mean peak concentration of propranolol (90 +/- 12 ng/ml versus 151 +/- 23 ng/ml) (p < 0.025), in the absorption constant (1.43 +/- 0.21 h 1 versus 0.96 +/- 0.12 h-1) (p < 0.05), and in the area under concentration-time curve (802 +/- 129 ng/ml.h versus 492 +/- 73 ng/ml.h) (p < 0.05). No significant difference was seen in drug effect on the heart at 90 min. We conclude that propranolol is absorbed more slowly in ulcer patients than in healthy subjects, but this delay has no clinical effect after a single dose. PMID- 8362222 TI - Epidemiological features of type 22 echovirus infection. AB - During a 25-year observation period, isolates of type 22 echovirus were obtained from 109 patients. 92% of the patients were < 2 years old. Echovirus type 22 was isolated with peaks both during late summer and autumn, as enterovirus infections, and during the winter months and early spring, as respiratory viruses. Diarrhea was the most common symptom, followed by obstructive bronchitis and, less often, CNS symptoms. Nosocomial infections were common. In a noticeable number of the children, maternal neutralizing antibodies were most probably present at the time of infection. The epidemiologic features of type 22 echovirus infections with regard to age and seasonal distribution, contagiousness and a relative lack of protection by neutralizing antibodies differed from most enterovirus infections. PMID- 8362223 TI - Patients treated in hospital for infectious mononucleosis and risk of cancer. AB - The risk of cancer was evaluated in a cohort of 1,234 patients with severe infectious mononucleosis between 1954 and 1983. The diagnosis of mononucleosis was confirmed by reviewing patient records. The observed numbers of cancer cases up to 1988 were obtained through record linkage from the Finnish Cancer Registry, which is nationwide and population-based. There were 11 cases of cancer in the cohort, as against 17.4 expected on the basis of the 24,288 person-years at risk and of incidence rates specific for age, sex and period in the area. This gives a standardized incidence ratio of 0.6 (95% confidence interval 0.3-1.1). There was only 1 lymphoma case. No malignancies were diagnosed during the first 5 years after infectious mononucleosis. The results indicate that infectious mononucleosis with severe symptoms does not imply an increased risk of cancer. PMID- 8362224 TI - HIV-antibody testings among injecting drug users (IDUs) in the Stockholm area, 1984-91: information compiled from testing laboratories. AB - The available information about testings for HIV antibodies in injecting drug users (IDUs) carried out in Stockholm between 1984 and 1992 has been compiled. These testings were carried out mainly in special settings. The use of codes (the first 2 digits giving the age and the last 4 the 6 and checking figures in the individual's personal identity number) precluded exact identification of individuals; in most cases, however, complementary information made it possible to recognize patients at follow-up. The data indicated that 9,150 persons associated with current or previous drug addiction were tested. The first extensive testings were performed in 1985 and 1986. After this period, 4,500 persons were retested. 11% of the IDUs tested in 1984-85 were found to be HIV antibody-positive. After 1988, 1% were estimated to seroconvert each year. While in the first phase the heroin users predominated among those infected, in later years the rates of newly diagnosed infections became similar for all types of IDUs. The age profiles of the IDUs tested were similar up to 1988, after which there was an indication that also younger persons had entered the scene. However, the infected IDUs discovered belonged mainly to the 'old' cohort born between 1950 and 1960. PMID- 8362226 TI - The C-reactive protein responses in HIV-infected patients with pneumonia. AB - The acute phase C-reactive protein (CRP) was measured in serum of HIV-infected patients suffering from Pneumocystis carinii pneumonia (PCP) (32 patients), bacterial pneumonia (10 patients), and in 19 immunocompetent patients with bacterial pneumonia. The HIV-infected patients with bacterial pneumonia had a significantly lower CRP level than the immunocompetent patients (50% versus 95% had an s-CRP level > 80 mg/l). No significant difference was found in the CRP response to P. carinii or bacteria in HIV-infected patients with pneumonia due to these microorganisms (20% versus 50% had s-CRP > 80 mg/l). In the group of PCP patients, a significantly lower CRP level was found in those with CD4 positive lymphocyte counts below 50 x 10(6)/l. There was no correlation between the CRP response and the severity of the PCP as estimated by the degree of hypoxia. We conclude that the CRP level cannot be used to discriminate between PCP and bacterial pneumonia in HIV-infected patients. PMID- 8362225 TI - Screening for anti-HIV and HBsAg in pooled sera from a clinical chemistry section as a tool for epidemiological survey. AB - With the aim of estimating the unknown spread of HIV into the general society, a program for testing pooled routine sera from a clinical chemistry laboratory has been tried. Serum samples obtained from the daily inflow of blood tubes at the Clinical Chemistry Laboratory, Malmo General Hospital, and not labelled as risk samples for blood-borne infection(s), were collected and pools of up to ten sera each were constructed according to a special protocol. All serum pools were screened for anti-HIV and HBsAg. During the 32-months period of the study 3,016 serum pools from men and the same number from women were collected and analysed. These pools together contained sera from 26,468 male and 26,891 female patients, respectively. Altogether 33 male and 2 female pools were found anti-HIV positive. Anti-HIV-positive males appeared in all age groups, without significant difference between the groups. Two female pools from the age group 15 to 24 years were anti-HIV positive; these samples were drawn during the last year of testing. HBsAg was detected in 189 male and 129 female pools. From 1989 to the first half of 1991 the mean anti-HIV prevalence among the male samples investigated was 0.10%, with 95% confidence limits from 0 to 0.25%. If the upper confidence limit is exceeded in the future, this could be a warning of increased spread of HIV of in society. PMID- 8362227 TI - Detection of pneumococcal capsular antigen in the presence of penicillin in vitro. AB - Eight strains of Streptococcus pneumoniae were tested in vitro for their ability to produce capsular antigen in the presence of penicillin. It was found that, provided 10(6) to 10(7) pneumococci/ml were present, capsular antigen could be detected during the 72 h in which the experiment was conducted, irrespective of whether penicillin was added at 0 h or 8 h, and even when no viable pneumococci remained. When fewer pneumococci were present, capsular antigen could not be detected at any time in the presence of penicillin. Control cultures, without penicillin, yielded detectable capsular antigen only when the threshold value of 10(6)-10(7) pneumococci/ml was reached. It is concluded that the presence of penicillin does not influence the detection of pneumococcal capsular antigen, but demonstration of this antigen is totally dependent on the number of pneumococci present. PMID- 8362228 TI - Erythromycin treatment is beneficial for longstanding Moraxella catarrhalis associated cough in children. AB - The benefits of antibiotic treatment and a nasopharyngeal culture in children with longstanding cough were analysed in a prospective randomized open study. Clinically suspected pertussis was excluded. Of 40 children given erythromycin for 7 days, 35 (88%) recovered in one week, compared with 17/47 (36%) untreated (p < 0.0001). Erythromycin eliminated Moraxella catarrhalis from the nasopharynx in 21/31 children (68%), compared with spontaneous disappearance in 7/35 (20%) untreated controls (p < 0.001). Purulent bronchitis or otitis media occurred in 2 children (5%) in the treatment group and in 21 (45%) in the control group (p < 0.01). To evaluate the clinical role of isolated pathogens, the 47 untreated subjects were studied. Seven of 35 children harbouring M. catarrhalis recovered, compared with 8/12 in whom this bacterium was absent (p < 0.01). No correlation was found between the isolation of Haemophilus influenzae or Streptococcus pneumoniae and the clinical outcome. Children with persistent cough > 10 days may benefit from erythromycin treatment. M. catarrhalis in the nasopharynx indicates prolonged symptoms and increased risk of bacterial complications. PMID- 8362229 TI - Comparative studies on pharyngeal carriage of Neisseria meningitidis during a localized outbreak of serogroup C meningococcal disease. AB - An outbreak involving 20 cases of serogroup C meningococcal disease, predominantly among teenagers, occurred over a 7-month period in the Randers area of Denmark. The cases were caused by serogroup C:2a:P1.2 sulphonamide-resistant strains. The available evidence was against the transmission being related to particular schools. The outbreak was experienced as 3 clusters. At 2 schools involved in the first and the third cluster of the outbreak, 351 students were examined regarding pharyngeal carriage of meningococci, 282 of whom were tested again 17 weeks later; 308 students attending two similar schools in a nearby area were examined once. The majority of strains isolated from group C carriers in the high-risk area were serologically indistinguishable from the outbreak strain (13/14 = 95%), but less often sulphonamide-resistant (5/13 = 38%). In both areas, the overall rate (30%), the overall group C rate (3%), the carrier rate for the outbreak strain (1%) were the same. The attack rate for the outbreak strain differed significantly: 1/40 in the high-risk area versus 1/2,500 in the normal risk area. No conditions that might explain this difference were revealed. Immediately after recognition of the first and the third cluster, 780 and 13,300 students, respectively, were vaccinated with meningococcal polysaccharide vaccine A+C. It was concluded that the definition of target groups for vaccination should be liberal, because the "at risk" population may be difficult to recognize at the onset of an outbreak. PMID- 8362230 TI - Deep obstetrical and gynecological infections caused by non-typeable Haemophilus influenzae. AB - Six patients with deep obstetrical and gynecological infections due to non typeable Haemophilus influenzae are presented. 3 patients had tubo-ovarian abscesses, 2 septic abortions and 1 postpartum sepsis. All our patients with tubo ovarian abscesses had used intra-uterine contraceptive devices until admission and all had a protracted course of illness. Both patients with septic abortion had a severe course, one of them with disseminated intravascular coagulation demanding treatment in the intensive care unit. The patient with postpartum infection had a milder course. The possibility of infection with H. influenzae and the emergence of beta-lactamase producing strains warrant adequate culture procedures in women with obstetrical and gynecological infections in order to ensure proper treatment. PMID- 8362231 TI - Significant decrease of gram-negative anaerobic bacteremia in a major hospital from 1967-73 to 1981-89: an effect of the introduction of metronidazole? AB - Declining rates of anaerobic bacteremia are reported from medical centres all over the world. At Odense University Hospital the frequency of Gram-negative anaerobic bacteremia decreased from 1.62% in 1967-73 to 0.83% in 1981-89 (p < 0.001). Metronidazole prophylaxis prior to bowel surgery seems to be the most important explanation, as the association of Bacteroides bacteremia with surgery decreased from 80% to 48% (p < 0.01) and no cases of Bacteroides bacteremia occurred during metronidazole treatment without the presence of abscess or gangrene. A contributory factor may be improved methods for abscess localization and drainage. Other drugs having an effect on anaerobes seem of minor importance. A new category of patients seems to be those who have undergone aorto-femoral bypass operation for aneurysm of the aorta. They contract anaerobic Gram-negative bacteremia from infected hematomas or intestinal gangrene. PMID- 8362232 TI - Factors affecting prognosis of neonatal tetanus. AB - Neonatal tetanus is associated with a high mortality rate, despite intensive care. Although it can be prevented by immunization of expectant mothers and by good hygiene and asepsis during delivery, neonatal tetanus is still a common cause of neonatal mortality in underdeveloped countries. In our study, hospital records of 133 newborns with neonatal tetanus were evaluated to identify the possible factors affecting prognosis of neonatal tetanus; 79 were males and 56 females, and 54 (41.6%) of the 133 died. Sex and birth weight did not affect the prognosis. As a result of our study, we found that age on admission < 10 days, symptoms < 5 days and presence of risus sardonicus and fever indicate a poor prognosis in neonatal tetanus. PMID- 8362233 TI - Management of indwelling central venous catheters in pediatric cancer patients with fever and neutropenia. AB - This prospective study comprises 97 episodes of fever and neutropenia in children with cancer and central venous access. In 76% of episodes, patients had a Broviac Hickman-like catheter, and in 24% a totally implanted venous access chamber system. The need for catheter removal during a febrile infection was 0.32/1000 catheter days, and the documented sepsis rate was 0.59/1000 catheter days. Our data indicate that 94% of episodes of fever and neutropenia in total, 78% of documented septicemias, and 97% of fevers of unknown origin were curable with broad-coverage antimicrobial therapy without removing the central venous line. Totally implanted chambers had a lower infection rate than catheters of Broviac Hickman type. PMID- 8362234 TI - Susceptibility of respiratory tract pathogens in Finland to cefixime and nine other antimicrobial agents. AB - The in vitro activity of cefixime and 9 other orally used antimicrobial agents against 545 selected clinical respiratory tract pathogens was tested using the plate-dilution method. Of the strains tested, 144 were Haemophilus influenzae strains, 151 group A streptococci, 105 pneumococci and 145 Moraxella catarrhalis isolates. Ciprofloxacin was the most active drug, with a minimal inhibitory concentration (MIC) of < 0.06 mg/l for more than 87% of the isolates. With cefixime, a MIC of 0.06 mg/l inhibited 55% of the strains tested and a MIC of 1.0 mg/l inhibited all except one of the 545 strains. One pneumococcal strain was resistant to cefixime. Beta-lactamase producing H. influenzae and M. catarrhalis strains were clearly more susceptible to cefixime than to other oral cephalosporins (cephalexin, cefaclor, cefuroxime). However, penicillin, ampicillin and cefuroxime were more effective against beta-hemolytic streptococci and pneumococci than was cefixime. The new third generation cephalosporin, cefixime, showed markedly better in vitro activity against certain major respiratory tract pathogens than the other peroral antimicrobials commonly used against respiratory tract infections. PMID- 8362235 TI - Pneumocystis carinii pneumonia presenting as an upper lobe cavity after aerosolized pentamidine prophylaxis in an HIV-infected patient. AB - We describe an atypical diagnostic feature of a breakthrough Pneumocystis carinii pneumonia (PCP) during primary prophylaxis with aerosolized pentamidine. Our case disclosed infiltrates restricted to the left upper lobe. After 2 weeks a solitary cavity developed. Diagnosis was easily established by bronchoalveolar lavage when performed in the affected segment bronchus. Cavitation clearly demonstrated localized infection, with tissue destruction as one main pathogenetic pattern of a breakthrough PCP during aerosolized pentamidine prophylaxis. PMID- 8362236 TI - Fatal disseminated infection by Scedosporium inflatum after bone marrow transplantation. AB - A case of disseminated infection caused by Scedosporium inflatum is reported in a patient undergoing autologous bone marrow transplantation for acute myeloblastic leukemia. The fungus was isolated from a blood culture and necropsy studies showed a disseminated infection involving numerous organs. In vitro studies showed the isolate to be resistant to amphotericin B, 5-fluorocytosine, ketoconazole and miconazole. PMID- 8362237 TI - Nasal administration of IgA to individuals with hypogammaglobulinemia. AB - Many immunodeficient patients constantly carry non-typable Hemophilus influenzae (NTHI) in the nasopharynx, despite seemingly adequate antibiotic therapy. We have studied the effect of nasal administration of IgA on nasopharyngeal colonization in 5 patients with hypogammaglobulinemia, with a productive cough, especially in the mornings, who were constant carriers of NTHI in the nasopharynx, and had IgA, 1 ml 6 times/day, given nasally for 14 days. Nasopharyngeal cultures were obtained on days 0, 7, 14 and 28. Two of the patients became culture-negative during the treatment, and the cough was alleviated in all patients. PMID- 8362239 TI - Genetics and male sexual orientation. PMID- 8362238 TI - Absence of human T-lymphotropic retrovirus type-1 (HTLV-1) in different populations of Mongolia. AB - The prevalence of human T-lymphotropic retrovirus type-1 (HTLV-1) was surveyed in Mongolia. A total of 1100 blood samples from different ethnic groups of the Mongolian population were examined for the presence of antibodies to HTLV-1 by serological tests using particle agglutination and immunofluorescence. All sera tested proved negative and Mongolian populations are therefore considered to be free from HTLV-1 infection. PMID- 8362240 TI - Genetics and male sexual orientation. PMID- 8362241 TI - A heavy ion accelerator gears up to fight cancer. PMID- 8362242 TI - Cholesterol and the Golgi apparatus. PMID- 8362243 TI - DNA conformation-induced activation of an enediyne for site-specific cleavage. AB - Neocarzinostatin chromophore (NCS chrom) was found to induce site-specific cleavage at the 3' side of a bulge in single-stranded DNA in the absence of thiol. This reaction involved the oxidative formation of a DNA fragment with a nucleoside 5'-aldehyde at its 5' terminus and generated an ultraviolet light absorbing and fluorescent species of post-activated drug containing tritium abstracted from the carbon at the 5' position of the target nucleotide. The DNAs containing point mutations that disrupt the bulge were not cleavage substrates and did not generate this drug product. Thus, DNA is an active participant in its own destruction, and NCS chrom may be useful as a probe for bulged structures in nucleic acids. PMID- 8362244 TI - Rat annexin V crystal structure: Ca(2+)-induced conformational changes. AB - Annexins are a family of calcium- and phospholipid-binding proteins implicated in mediating membrane-related processes such as secretion, signal transduction, and ion channel activity. The crystal structure of rat annexin V was solved to 1.9 angstrom resolution by multiple isomorphous replacement. Unlike previously solved annexin V structures, all four domains bound calcium in this structure. Calcium binding in the third domain induced a large relocation of the calcium-binding loop regions, exposing the single tryptophan residue to the solvent. These alterations in annexin V suggest a role for domain 3 in calcium-triggered interaction with phospholipid membranes. PMID- 8362245 TI - Determining whitefly species. PMID- 8362246 TI - Hemostasis in liver transplantation: the surgeon's view. PMID- 8362247 TI - Hemostasis in advanced liver disease. PMID- 8362248 TI - Coagulation and fibrinolysis in orthotopic liver transplantation: current views and insights. AB - Bleeding in OLT is related to two different mechanisms. There is no doubt that the extensive surgical trauma plays a critical role in the origin of serious bleeding. However, this bleeding can be aggravated by defects in the hemostasis system. Hemostasis defects can be divided into those present before the operation and secondary to the underlying liver disease and those originating during the operation. Intraoperative defects can be classified according to the three main systems of hemostasis: coagulation, fibrinolysis, and platelet function. Serious problems with coagulation are clearly related to the quality of the graft and are less frequent now since better graft preservation techniques have been introduced. Adequate intraoperative monitoring and substitution therapy with plasma products is also important in controlling coagulation defects. However, problems resulting from hyperfibrinolysis seem to be of clinical importance, especially during the anhepatic stage and after graft reperfusion. While lack of hepatic clearance seems to be an important cause of t-PA increase during the anhepatic stage, enhanced release may be important for the rise after graft reperfusion. There is also evidence that decreased platelet numbers and function, especially after graft reperfusion, play a role. The clinical relevance of this finding remains to be elucidated. Finally, it has recently been demonstrated that antifibrinolytic agents may reduce intraoperative blood loss. However, the effect of aprotinin and other antifibrinolytic agents has still to be confirmed by randomized clinical studies. Future scientific research should focus on the mechanisms underlying the hemostasis defects. It can be expected that these efforts may finally result in a further reduction in the usage of blood products during liver transplantation. PMID- 8362249 TI - Thrombocytopenia and platelet dysfunction in orthotopic liver transplantation. PMID- 8362250 TI - Hemostasis in heterotopic liver transplantation. PMID- 8362252 TI - Retrospective statistical analysis of coagulation parameters after 250 liver transplantations. AB - Extensive transfusion of blood components as a typical feature of OLT has been described by many authors. The perioperative requirement for transfusion, however, follows a downward trend, although the indications for OLT have been extended. Functional disturbances such as hyperfibrinolysis or platelet dysfunction, demonstrated by laboratory tests, such as platelet counts, PT, aPTT, TT, fibrinogen, and ATIII are often used to direct the transfusion of blood components, although preoperative data give insight only into the insufficient function of the old liver, which will be explanted and replaced by the donor graft. We have described a retrospective statistical analysis of laboratory data, clinical data, and perioperative blood requirements from 250 liver transplantations performed in our hospital from 1988 to 1992. The OLT was performed according to the usual surgical methods using a venovenous bypass system. Intraoperatively, volume was restored with packed RBC and FFP according to hemodynamic data, hemoglobin, and diuresis; clotting data were not used as indications for blood replacement. This analysis demonstrated that neither preoperative nor intraoperative clotting parameters were able to allow a prediction of the intraoperative requirement for transfusion of blood components; these findings parallel those of previous reports. With respect to other studies showing that perioperative transfusion rates correlated with postoperative infections and mortality, we strongly suggest that perioperative clotting measures as indicators for transfusion requirement should be analyzed with caution. Whether other diagnostic methods such as TEG are useful alternatives has to be determined. PMID- 8362251 TI - Hemostasis in children undergoing liver transplantation. AB - We reviewed the records of 200 children who underwent 238 orthotopic liver transplantations in order to determine which preoperative factors could predict intraoperative blood loss. A coagulation abnormality score (CAS) was calculated by allowing one point for each abnormality in six preoperative coagulation tests. The mean CAS values were significantly greater in children suffering from fulminant hepatic failure (Fulm) or post-necrotic cirrhosis (PNC) and those having retransplantation (ReTx) than in those with disease of other etiologies. No correlation was found between the CAS and the mean blood requirements in the different etiology groups. According to the amount of blood transfused, children could be divided in two groups. Group 1 were those with biliary atresia and ReTx, who received more than 200 ml/kg. Group 2 included those with PNC, Fulm, metabolic diseases, and Alagille syndrome and Byler disease, who received less than 140 ml/kg. The mean CAS was significantly lower and the PT significantly better in Group 1. We conclude that preoperative coagulation tests were weak predictors of intraoperative bleeding. The etiology of the underlying liver disease and previous abdominal surgery play an important role in the occurrence of severe bleeding. Intraoperatively, children presented the same hemostatic changes as adults. PMID- 8362253 TI - Intraoperative monitoring and postoperative reevaluation of hemostasis in orthotopic liver transplantation. PMID- 8362254 TI - Laboratory measures of hemostasis for monitoring liver graft function. PMID- 8362255 TI - Clinical use of synthetic antifibrinolytic agents during liver transplantation. PMID- 8362256 TI - Antithrombin III replacement in orthotopic liver transplantation. PMID- 8362257 TI - Role of protein S in orthotopic liver transplantation. PMID- 8362258 TI - The "lytic state" during orthotopic liver transplantation: plasminogen activators and other protease activities. PMID- 8362259 TI - Recovery of antithrombin III in patients undergoing orthotopic liver transplantation after administration of an antithrombin III concentrate. PMID- 8362260 TI - Biochemical and pharmacologic profile of defined molecular weight fractions of heparin. PMID- 8362261 TI - Venous thromboembolism after hospital discharge. AB - Several methods of prophylaxis have significantly reduced the risk of developing VTE during hospital admission. There is a current tendency toward a reduction in the hospital stay, which does not necessarily mean that patients are protected from experiencing thrombotic complications after leaving the hospital. A number of patients will develop DVT and PE after hospital discharge if prophylaxis is prematurely discontinued while they persist at risk. Further studies are necessary to establish whether extending prophylaxis beyond discharge will reduce the rate of late-onset thromboses and which are the best prophylactic alternatives for the different patient groups at risk. Meanwhile, it is our standard of practice to utilize a combination of GES and either low-dose heparin or warfarin, at least for 3 or 4 weeks after discharge in high-risk patients. In countries where low molecular weight heparins are available, these agents represent an attractive alternative to unfractionated heparin because of their better dosage schedule and safety profile. PMID- 8362262 TI - Venography used for deep vein thrombosis screening of asymptomatic patients undergoing total hip replacement. PMID- 8362263 TI - Endpoints for diagnosis of postoperative thromboembolism in hip fracture surgery. PMID- 8362264 TI - Measurement of beta-thromboglobulin and platelet factor 4 to follow up patients with artificial heart valves. AB - Efficient antithrombotic therapies are necessary for the prevention of thrombotic complications in patients with artificial heart valves. Antiplatelet drugs are commonly used since platelet activation is a feature frequently found in these pathologic conditions. The measurement of beta TG and PF4 is useful for the diagnosis of platelet activation, which may increase the thrombotic risk. Two commercially available ELISA kits for beta TG and PF4 were tested and compared with the corresponding RIA methods used previously. Coefficients of correlation were 0.976 for beta TG and 0.985 for PF4. Both methods gave identical results, although RIA was expressed in nanograms per milliliter, whereas ELISA results were in international units per milliliter by comparison with International Standards. For both parameters 1 IU/ml was found to be almost equal to 1 ng/ml. beta TG was elevated in the group of patients with heart valves (57.28 IU/ml); so was PF4 but to a lesser extent (11.28 IU/ml). The mean concentrations on a normal population were, respectively, 22.40 (+/- 5.15) IU/ml and 4.10 (+/- 2.02) IU/ml. The monitoring of patients with heart valves allowed the identification of two distinct groups: those who had persistent elevated levels of beta TG and PF4, and those whose levels of the same parameters were in the subnormal ranges. All the thrombotic complications were observed in the first group and were preceded by an elevation of platelet markers. beta TG was the most predictive and correlated closely with the evolution of the clinical state. Cerebrovascular accidents were the commonly observed complications. These patients were treated by hypocoagulant therapy and with antiplatelet drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362265 TI - Antithrombotic activities of aprosulate sodium (LW 10082) and its neutralization by protamine. PMID- 8362266 TI - Antithrombotic effect and clinical potential of defibrotide. PMID- 8362267 TI - Contrast media influence on thrombotic risk during coronary angioplasty. PMID- 8362268 TI - Antithrombin III- and heparin cofactor II-mediated anticoagulant and antiprotease actions of heparin and its synthetic analogues. AB - A chemically synthesized pentasaccharide, a specific ligand for AT III, and a synthetic, sulfated bis-lactobionic acid amide, a ligand for HC-II, were studied along with heparin to determine the relative contribution of AT III and HC II in the inhibition of protease activation in plasma. The global clotting assays (PT, APTT, Heptest, TT), amidolytic anti-IIa and anti-Xa assays, and defined biochemical systems supplemented with purified AT III and HC II were used in this study. In the plasma-based assays, heparin exhibited strong inhibition in both thrombin and Factor Xa-based assays, whereas pentasaccharide was only active in Factor Xa-based assays and lactobionic acid was only active in thrombin-based assays. In the AT III supplemented systems, heparin was able to inhibit strongly both Factor Xa and thrombin, while pentasaccharide could only inhibit Factor Xa. Lactobionic acid was ineffective at mediating its actions through AT III. In the HC II-mediated inhibition of thrombin, heparin and lactobionic acid both had strong inhibitory actions. Pentasaccharide was ineffective in this assay. All three agents failed to inhibit Factor Xa via HC II. These studies suggest that specific synthetic analogues of heparin such as the pentasaccharide and lactobionic acid can be used to study the relative contributions of AT III and HC II in the control of protease activation during thrombogenesis. PMID- 8362269 TI - Comparative pharmacologic profile of a glycosaminoglycan mixture, Sulodexide, and a chemically modified heparin derivative, Suleparoide. PMID- 8362270 TI - Coacute heparin: a new simple monotest for monitoring heparin treatment. AB - Anti-factor Xa methods have been generally accepted for the monitoring of heparin treatment mainly due to their sensitivity to LMWH and excellent performance on automated equipment. When such equipment is not available, as in small laboratories or on the night shift, there is a need for a simple manual method. In the present method, activated Factor X and a chromogenic peptide substrate are colyophilized in plastic cuvettes under conditions that avoid reaction between the two constituents. The assay is performed accordingly. Plasma (200 microliters) is diluted in 3.0 ml predispensed Tris buffer containing dextran sulfate 8000 to avoid losses of heparin due to platelet factor 4, for example. The diluted plasma (400 microliters) is added to a cuvette. The reagents are rapidly dissolved and the reactions start. The rate of Factor Xa inhibition is proportional to the heparin activity. During the incubation, the substrate is also hydrolyzed by the remaining enzyme. This combination of reactions is insensitive to changes in temperature making it possible to perform the assay at room temperature. After 10 minutes incubation, the reaction is stopped by adding 400 microliters of 5% acetic acid. The absorbance is read in a well-calibrated photometer and the results plotted on a graph available in the kit. Eleven commercially available heparins have been tested with the assay and they all fell within a narrow range, showing the relevance of using a standard plot for all heparins. The LMWH behaved differently and it may also be that they demand different therapeutic strategies. PMID- 8362271 TI - A new approach in monitoring recombinant hirudin during cardiopulmonary bypass. PMID- 8362272 TI - Problems in financing the care of AIDS patients. AB - The problem of financing the care of patients with acquired immune deficiency syndrome (AIDS) has reached crisis proportions. How will the United States cope with paying for the care of AIDS patients, many of whom either are denied private insurance or simply do not have money to pay for medical care? This article discusses how each component of the U.S. health care financing system is attempting to minimize its financial exposure to AIDS. It presents remedies that have been suggested in the literature. Finally, it points out the flaws in the current system for dealing with people who suffer from catastrophic illnesses. PMID- 8362273 TI - A community-based approach to HIV case management: systematizing the unmanageable. AB - This article presents an analysis and typology of community-based care for a young Hispanic mother with acquired immune deficiency syndrome (AIDS). It develops a conceptual framework that examines retrospectively the needs generated by AIDS over time, the appropriateness of the services, and an assessment of the interventions. Community-based case management can effectively address some of the diverse and changing needs of AIDS patients and their families, such as bridging service gaps and fortifying patient and system strengths while minimizing their weaknesses. Community-based case managers may also be better equipped than hospital case managers to work with difficult patients and coordinate community- and hospital-based care. Conclusions are presented regarding the definition and implementation of community-based, culturally sensitive, family-centered human immunodeficiency virus case management, as well as the importance and difficulty of developing relationships among the family, health care providers, and institutions within the community. PMID- 8362274 TI - Testing the sexually abused child for the HIV antibody: issues for the social worker. AB - The frequency of HIV transmission to children and adolescents through sexual abuse is unknown. Because the incidences of HIV infection and of reported sexual abuse are both increasing, the transmission of HIV to children through sexual abuse may also be increasing. Social workers may have expanding roles in the decision-making process for testing and subsequent management of children infected with HIV through sexual abuse. This article discusses the benefits of identifying children who have been infected with HIV through sexual abuse and reviews guidelines for testing. Social workers can contribute to test decision making in instances when perinatal HIV transmission is a possibility, when it may be possible to test the assailant, and when parents or legal guardians insist on testing the child. Other issues discussed include family education and coping, physical education and support, social casework and research with pedophiles, and service needs for care and follow-up of children found to be HIV infected as a result of sexual abuse. PMID- 8362275 TI - Influence of education on self-perceived attitudes about HIV/AIDS among human services providers. AB - Participants in a number of different HIV/AIDS educational programs, varying in content, length of course, and student audience, were surveyed to determine if education could help reduce fear and increase comfort in work with HIV/AIDS clients. It was hypothesized that attitude scores would improve following exposure to the educational programs. A retrospective pretest-posttest survey design consisting of Likert statements was used. A t test for paired samples determined if attitude scores improved following exposure to the educational programs. An analysis of variance determined if significant differences in pretest and posttest scores existed among the groups. Within groups, there was a positive increase in self-assessed attitude scores. Multiple group comparisons indicated significant differences between groups that appear to be related to program content and length. Workplace risk and whether a program was elective may have also been factors affecting attitude. PMID- 8362276 TI - Judgments of personal responsibility for HIV infection: an attributional analysis. AB - This article examines the influence that attributions of personal responsibility for infection with the human immunodeficiency virus have on service and policy responses to the epidemic. A model of attributed responsibility is proposed that classifies social judgments of another person's behavior that take into account the extent to which the behavior caused the situation, the person knew or should have known the potential consequences of the behavior, the person intended to engage in the behavior, and factors over which the person had little or no control might have influenced the behavior. Research has shown that attributions of responsibility lead to increased anger, decreased empathy, and a diminished willingness to offer help to others in need. The author concludes that awareness of attributions of responsibility may help reduce their discriminatory effects at all levels of social work practice. PMID- 8362277 TI - AIDS and social work: the ethics and civil liberties agenda. AB - Social workers are becoming increasingly involved in casework and social policy debate related to the acquired immune deficiency syndrome (AIDS) crisis. To enhance their delivery of services and contribution to policy formulation, social workers need to be familiar with a wide range of ethical and civil liberties issues that have been generated by the AIDS epidemic. This article provides an overview of six major ethical and civil liberties issues pertaining to social work practice related to AIDS: (1) mandatory screening and testing of clients for the human immunodeficiency virus (HIV), (2) client access to health insurance, (3) professionals' duty to treat HIV-infected clients, (4) privacy and confidentiality, (5) client involvement in AIDS research, and (6) relevant legal issues. Implications for social work practice are highlighted, particularly with respect to protecting clients' rights and formulating a social action agenda. PMID- 8362278 TI - Differences among adolescent, young adult, and adult callers of suicide help lines. AB - The authors examined data on 165 adolescents (ages 12 to 19), 65 young adults (ages 20 to 26), and 175 adults (ages 27 and older) who called two suicide help lines in Los Angeles County during a two-week period. One crisis line is operated by a major suicide prevention center; the second is a crisis help line for adolescents that offers peer counselors. Adults and young adults reported depression as the primary reason for contemplating suicide; adolescents reported interpersonal problems. Despite the chronic nature of the presenting problems, referrals were provided to fewer than one-half of the adults and young adults and fewer than one-third of the adolescent callers. Although the callers reported suicide ideation, a very small percentage fell into the high-risk categories with regard to degree of suicide planfulness and lethality of chosen method. PMID- 8362279 TI - Support systems and stress reduction among workers caring for dependent parents. AB - This study investigated the impact of three types of support--from family and friends, the workplace, and community services agencies--on the perceived stress and health outcomes of 133 employed caregivers of dependent parents. The stressor support-stress-reaction model guided the research. Support from family and friends and community agencies was found to buffer the negative impact of caregiving and work and family role strain, and a supportive work environment was one predictor of lessened physical strain. PMID- 8362280 TI - Reconstruing codependency using self-in-relation theory: a feminist perspective. AB - Judging from advertisements for professional books, continuing education workshops, and speakers, social workers appear to believe that codependency is a problem about which they should be knowledgeable. This article traces the evolution of the codependency construct and its burgeoning popularity in the 1980s. It critically examines codependency from the perspective of researchers who have found little empirical support for the constellation of characteristics used to define the term and from the perspective of feminist analysis. In addition, the article analyzes the assumptions about health and relationships that are embedded in the concept of the codependency and contends, from the perspective of self-in-relation theory, that the concept does not provide a useful framework for social work conceptualization and intervention with women. PMID- 8362281 TI - Economic questions concerning leprosy control. PMID- 8362282 TI - Serological diagnosis of Toxoplasma gondii infection in women associated with gyneco-obstetric problems. AB - The latex agglutination test (Toxoreagent) was used to detect the sero-prevalence of Toxoplasma gondii in 302 Bangladeshi women who were under treatment for various gyneco-obstetric problems at the Mymensingh Medical College during January to June 1991. The over-all sero-prevalence rate was 15.89%, of which 6.25% reacted at 1:32, 33.33% at 1:64, 16.67% at 1:128, 22.92% at 1:256, 6.25% at 1:512 and 14.58% at 1:1024. The positivity rate of 18.60% recorded in women between 31 and 40 years was insignificantly (p > 0.05) higher than that of 15.44% in women between 17 and 30 years of age. Over-all 26.49% of infections resulted in abortion, 6.62 in stillbirths and 30.79% in dystocia, of which 20.0%, 30.0% and 7.53% women had positive titers to T. gondii, respectively, whereas 17.43% women with normal live births had also positive titers to T. gondii. The over-all prevalence rate of abortion in association with T. gondii infection was 5.30% which was higher than the rates of stillbirths (1.99%) and perinatal death (0.66%). It is concluded that toxoplasmosis can cause abortion, stillbirths and perinatal death in Bangladeshi women. PMID- 8362283 TI - Immunoproliferative small intestinal disease (IPSID) in Thailand. AB - Immunoproliferative small intestinal disease (IPSID) is prevalent in the Mediterranean region and in many Third World countries but is rare in Southeast Asia. Between 1980-1990, 4 cases of IPSID were admitted to Ramathibodi Hospital, Bangkok. Three were males and the mean age was 32 +/- 20.2 years. All patients presented with chronic diarrhea of 7 months to 6 years duration, and weight loss of 15 to 31 kg. All were malnourished, three cachectic, and one patient showed growth retardation. Intestinal parasites were found in all cases: two had multiple infections and three had uncommon protozoal infections (coccidium, cryptosporidium). Barium radiographs revealed intestinal mucosal fold thickening with malabsorption pattern in all cases. Alpha chain IgA was detected in one patient. The remainder underwent exploratory laparotomy and the histological finding was of plasma lymphocytic infiltration of the small intestinal mucosa. All patients responded to oral tetracycline with complete remission occurring in one case. During the follow-up period, 3 cases had progressive retractable clinical courses but all died 2 to 5 years after the diagnosis. The causes of death in these patients were secondary bacterial infection (1 case), intestinal tuberculosis (1 case), fungal infection (1 case) and immunoblastic sarcoma in another case. The results of this study confirm the occurrence of IPSID in Thailand. IPSID responds to oral antibiotic therapy and complete remission may be achieved during the early reversible benign phase, thus an awareness of its occurrence is of clinical importance. PMID- 8362284 TI - The occurrence of salmonellae in bean sprouts in Thailand. AB - Detection of Salmonella spp. in 344 samples of bean sprouts was attempted by pre enriched in buffered peptone water (BPW) or lactose broth (LB) at 37 degrees C, followed by selective enrichments, selenite cystein broth (SCB) and Rappaport medium (RV) at 43 degrees C. Four selective media, bismuth sulphite agar (BSA), brilliant green agar (BGA), Salmonella-Shigella agar (SSA) and MacConkey agar (MA) were used for isolation. Salmonellae were isolated from 30 (8.7%) samples. They were serotypes lexington (56.7%), orion (16.7%), senftenberg (16.7%), tennessee (3.3%), poona (3.3%) and weltevreden (3.3%). Pre-enrichment in LB, followed by enrichment in SCB and streaking on to BSA gave the highest recoveries. Fifteen of 30 strains isolated were sensitive to all 14 antibiotics tested. Seven strains were resistant to one, and a strains showed multiple resistance to 2-4 antimicrobial agents. PMID- 8362285 TI - Ileal perforation in typhoid: bacteriological and immunological findings. AB - In typhoid perforation patients, Salmonella typhi was isolated from blood in 4%, ileal contents in 23%, peritoneal pus in 13% and from mesenteric lymph nodes in 71%. While isolation of S. typhi was made from patients with less than 4 days of chloramphenicol therapy, cultures were negative from these sites after 5 days of therapy; however, S. typhi appeared to remain viable in the lymph nodes even after such therapy. All isolates of S. typhi were sensitive to chloramphenicol. Significant SAT titers (0 > or = 1/240) were obtained in only 7/21 (33%) of patients. The perforated group had lower geometric mean titers (0-1/138; H-1/46), when compared to matched patients with uncomplicated typhoid fever (0-1/476; H 1/148). This difference was significant (0- p < 0.005; H- p < 0.0025). The two groups (uncomplicated and perforated) showed no significant difference in total serum IgG, IgM and IgA or isohemagglutinin levels, indicating that the apparent hyporeactivity was not due to a generalized humoral immunodeficiency. Mesenteric lymph node histology showed hyporeactivity in both the T cell and B cell zones. These findings are discussed with the suggestion that S. typhi-specific host immunological hyporeactivity could be an explanation for these observations and a basis for the pathogenesis of perforation. Aerobic cultures of the peritoneal pus gave 39 isolates from 25 patients; the predominant isolates were Escherichia coli (24) and Klebsiella pneumoniae (12). On no occasion was S. typhi the predominant isolate. Gentamicin and kanamycin were the only two antibiotics which were consistently effective in vitro against the aerobic isolates from peritoneal pus. PMID- 8362286 TI - Pasteur oral cholera vaccine: studies of reactogenicity, clinical acceptability and immunogenicity in human volunteers. AB - Pasteur cholera vaccine consists of isolated antigenic fractions from V. cholerae El Tor Ogawa and Inaba. Enteric coated microgranules were prepared from antigen lyophilisate. Three doses of this vaccine were administered orally to 19 healthy young Thai adults at one week intervals. None of the volunteers experienced untowards reactions. The vibriocidal antibody responses manifested a significant antibody rise (> or = 4 fold) to serovar Inaba in 8 vaccinees (42.1%) and Ogawa in 4 (21.1%). Five and 6 vaccinees (26.3% and 31.6%) showed a > or = 4 fold rise of IgG and IgA anti-LPS, respectively. PMID- 8362287 TI - The effect of permethrin impregnated bednets on the incidence of Plasmodium falciparum, in children of north Guadalcanal, Solomon Islands. AB - The effect of permethrin impregnated bednets was studied for the first time amongst a large community in North Guadalcanal, Solomon Islands. The community was divided into two; one covered 23 villages with 860 people who were given bednets impregnated at 0.5 g/m2, and the other 20 villages with 520 people was used as control. Parasitological data were collected by regular prevalence surveys and examination of records of malaria patients who have sought treatment in clinics. Entomological data by landing catches using human bait. The entomological results showed a 71% reduction of Anopheles farauti. Even though there was no significant reduction observed with An.punctulatus, as the density was already very low, the number biting indoor was much lower than those outdoor of houses with treated bednets. Parasitologically there was a steady decline in the incidence between surveys with Plasmodium falciparum in the under 10 years old. Even though there was no significant reduction in the other variables measured, there was a steady increase in the clearance rate between surveys which might also be due to easy accessibility to chemotherapy. The study showed the significant beneficial effect of permethrin impregnated bednets, which was found to be still effective up to twelve months, against stable P. falciparum malaria in children. PMID- 8362288 TI - Studies on the effect of lambdacyhalothrin on Anopheles maculatus Theobald and its response to residual spraying at Jeram Kedah, Negeri Sembilan, Malaysia. AB - A field trial was carried out to study the effect of lambdacyhalothrin on Anopheles maculatus in trap huts in Jeram Kedah, Negeri Sembilan, Malaysia. Two trap huts were built, of which one was sprayed with lambdacyhalothrin at a dosage of 25 mg ai/m2 and the other served as control. Eight collectors commenced collecting mosquitos from 1900 to 2400 hours, two each indoors and outdoors. Bioassay was also carried out in the treated and control huts to determine susceptibility of adult mosquitos to lambdacyhalothrin. In the treated hut more mosquitos were present during the pre- spraying period. Lambdacyhalothrin gave a mortality of 100% against An. maculatus for 8 months. PMID- 8362289 TI - Mosquito larvae and associated macroorganisms occurring in gem pits in southern Tha Mai District, Chanthaburi Province, Thailand. AB - Aquatic field studies were conducted in Tha Mai District, Chanthaburi Province, Thailand. Larval habitats of Anopheles dirus were examined from November 1986 through June 1988 in 42 manmade gem pits. Larvae were found in pits containing clear water under full or partial shade. The abundance of different kinds of mosquito larvae were related to seasonal changes in these aquatic habitats. Variations in An. dirus density and occurrence were related to predators populations, ie Notonectidae and fish. PMID- 8362291 TI - Laboratory evaluation of two commercial repellants against Leptotrombidium fletcheri (Acari: Trombiculidae). AB - Two commercial repellants were evaluated in the laboratory against Leptotrombidium fletcheri chiggers. The active ingredient in one was DEET and in the other was citrus oil. Excito-toxicity effect was studied and it was determined by the time ("escape time") chiggers took to move off filter papers treated with the repellants. All chiggers exposed on filter papers treated with DEET died and did not move off the treated papers. None of the chiggers that were placed on papers treated with citrus oil were killed. Escape times on papers treated with a 2-sec spray of citrus oil were longer than those for the 4- and 8 sec sprays. The weights of citrus oil deposited increased with increasing spray times. Electron microscopy showed that the repellants had no effect on the texture of the filter papers. It was concluded that the spray containing DEET was more effective; however, both repellants should be further evaluated under field conditions for protection against chigger bites. PMID- 8362290 TI - Biting density, behavior and age distribution of Culex quinquefasciatus, say in Mysore City, India. AB - The seasonal abundance, night indoor biting behavior and parity of Culex quinquefasciatus were investigated for a period of one year from June 1988 to May 1989 in Mysore City. Twelve-hour night-time biting catches were carried out from 1800-0600 hours at four selected urban localities. The biting cycle revealed that Cx. quinquefasciatus was active throughout the night, with peak activity at 2200 2300 hours. The biting proportion of nulliparous and parous mosquitos during different hours of the night showed that nulliparous mosquitos increased from 1800 to 0600 hours (dusk to dawn), while parous mosquitos (aged) decreased from early night to the morning. One major and two minor biting peaks were encountered here. The maximum density noticed was during March 1989 (147.5 per man night) and the lowest was during July 1988 (58.3 per man night). The biting behavior/density of this important urban mosquito vector under the existing climatic conditions are discussed in the light of the earlier reports elsewhere. PMID- 8362292 TI - Natural parasitic infection of the golden apple snail, Pomacea canaliculata. AB - Golden apple snails, Pomacea canaliculata, were collected once a month during a year to search for their natural parasites. The collections were made at two localities having different ecological environments. Of 576 collected snails from a canal, 176 individuals (30.6%) were infected by three groups of metacercariae. These parasites were amphistome, distome and echinostome metacercariae, which had prevalences of 23.5, 19.5 and 0.5%, respectively. The incidence of infection was highest (68.4% in October) when the snail population was composed of the old, juvenile and young Pomacea. Amphistome metacercariae were found most frequently and echinostome metacercariae the least frequently; both parasites were localized in the foot muscle of the snails and had a Shannon index of zero. The range of amphistomes was 1 to 115 with the mean +/- SD of 1 +/- 2 and 95% CL of 1, 2. Distome metacercariae were found primarily in the heart (range: 1-13), and also in the foot muscle (range: 1-5) and kidney (range: 1-14), with a Shannon index of 0.4. The means +/- SD (with 95% CL) were 3 +/- 4 (95% CL = 1, 5), 3 +/- 4 (95% CL = 2, 4) and 2 +/- 1 (95% CL = 1, 2) for the foot muscle, heart and kidney, respectively. The snails from a pond, another locality, had a low proportion of infected individuals. Of 605 snails, only 24 individuals (4.0%) were infected, with the prevalence of amphistomes, distomes and echinostomes being 0.8, 1.8 and 2.1%, respectively. The incidence of infection for each month was zero or less than 10%, except in May when it was 30.2%. PMID- 8362293 TI - Studies on the cobra neurotoxin inhibiting activity in an extract of Curcuma sp. (Zingiberaceae) rhizome. AB - A study was carried on the mode of action and some properties of a cobra neurotoxin inhibitor found in the extract of Curcuma sp. (Zingiberaceae). When the principal postsynaptic neurotoxin (STX) of the Thai cobra (Naja naja siamensis) was mixed with an aqueous extract of Curcuma sp. rhizome, the STX was inactivated as tested in mice or in vitro using a rat hemidiaphragm preparation. The 'neurotoxin inhibitor' ('NTxI') was found only in the water insoluble fraction of the rhizome extract. Using radioactively labeled neurotoxins, 125I STX and 3H-STX, it was demonstrated that the neurotoxin did not form a stable complex with the 'NTxI'; the inactivated neurotoxin remained in the supernatant of the reaction mixture. After inactivation by 'NTxI', the STX exhibited an unchanged molecular weight as judged by SDS-polyacrylamide gel electrophoresis and an unchanged isoelectric point in isoelectric focusing. Extraction of the Curcuma sp. rhizome with at least 0.2% Triton X-100 resulted in solubilization of a component capable of forming a soluble and stable complex with 3H-STX. By column chromatography on Sephadex G-200 in the presence of 0.1% Triton X-100, the toxin-binding compound was shown to have a molecular weight of about 150 kDa. This 150 kDa component was obtained by Triton extraction of the water-insoluble fraction, and much less from the water soluble fraction, of Curcuma sp. rhizome. It did not possess any carbohydrate side-chain capable of binding the lectin Concanavalin A. The time course of the 150 kDa-3H-STX complex formation was extremely slow (approx 22 hours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362295 TI - Snakebites at Maharat Nakhon Ratchasima Regional Hospital. AB - One hundred and ninety-nine victims of snakebite hospitalized at Maharat Nakhon Ratchasima Hospital between 1898 and 1991 were studied. The male:female ratio was 1.9:1 and their mean age (+/- SD) was 30.0 +/- 18.6 years. The most common of victims were farmers and laborers. Dead snakes were identified as follows: 72 were Trimeresurus sp. (36.2%), 36 were Naja kaouthia (17.6%), 4 were Bungarus fasciatus (2.0%), 1 were Colloselasma rhodostoma (0.5%) and 1 was Vipera russelli (0.5%). No death was noted among the victims bitten by Trimeresurus sp, C. rhodostoma and V. russelli. Fifty-eight victims exhibited complications, constituting 29.1%. Four cases died from the bite of N. kaouthia, 2 from B. fasciatus and 1 from unidentified snake. A total death rate was 3.5% (7 in 199 cases). The mean duration in the hospital for patients bitten by Trimeresurus sp. and N. kaouthia were 2.3 days and 2.0 days, respectively. In order to decrease the morbidity and mortality of snakebite victims in Nakhon Ratchasima Province, prevention and control of this entity should be emphasized in health education of local people, training programs on appropriate management of snakebites for the medical and paramedical personnel working in the remote rural district hospitals and health centers. In addition, antivenoms and other necessary medical supplies should be adequately provided. PMID- 8362294 TI - Some characteristics of hospitalized HIV seropositive patients in Myanmar. AB - Twenty-two hospitalized HIV seropositive patients were studied prospectively between July 1991 and January 1992. The majority of the patients were intravenous drug users (IVDUs). Their age ranged from 20 to 38 years with a male preponderance of 12 to 1. Anemia, lymphopenia and thrombocytopenia were observed in 100%, 36% and 41%, respectively. The common pathogens like malaria parasites, Mycobacterium tuberculosis, Entamoeba histolytica, Streptococcus and Salmonella were isolated/identified rather than opportunistic organisms. PMID- 8362297 TI - Urinary fibrin (-ogen) degradation products in Russell's viper (Daboia russelii siamensis) bite victims. AB - Serum and urine concentrations of fibrin (-ogen) degradation products (FDP) were estimated in 20 proven Russell's viper bite (RVB) cases with severe defribination. All patients had similar degrees of high serum FDP levels. However, the ten who developed into acute renal failure (ARF) had significantly (p < 0.001) higher urinary FDP levels than those who did not. The urinary FDP levels of ARF cases increased correspondingly with high serum FDP levels but not in cases without ARF. Serial comparison of serum and urinary FDP levels in RVB cases with severe defibrination may be of value in predicting the likelihood of developing ARF. The present study favored disseminated intravascular coagulation as the main cause of ARF in Myanmar RVB cases. PMID- 8362296 TI - Renal histopathology following Russell's viper (Vipera russelli) bite. AB - Renal lesions in ten patients following Russell's viper bite were studied. Renal biopsies were available in six and autopsies in four patients. Autopsied tissues from two cases of traumatic death served as controls. Both qualitative and quantitative changes in the glomeruli, tubules, interstitium and blood vessels were evaluated. Tubular necrosis was detected in five, tubular degeneration in nine, glomerular changes in nine and interstitial changes in four cases. Generally tissues from expired cases had more severe and extensive renal lesions than those that survived. PMID- 8362298 TI - Polymicrobial infective endocarditis with anterior spinal artery syndrome in a drug addict. PMID- 8362299 TI - An easy technique for histological sections of split intestinal tissue. PMID- 8362300 TI - The "P" in GMP--a major shift in growth monitoring program of a primary health care project. AB - Growth monitoring and promotion (GMP) is the monitoring of a child's growth to promote, maintain and restore health. The "P" in GMP relates to the promotive, preventive and curative actions which accompany the monitoring process. Data from two of the Primary Health Care field sites of The Aga Khan University, Essa Nagri and Azam Basti (squatter settlements), in Karachi for May 1989 was analyzed to determine the relationship between weight change and nutritional status. 21% of 2,838 children had a decrease in weight from April to May 1989. Children in Grade I malnutrition (n = 274) contributed much more to this decrease than children with Grades II and III (54 and 5, respectively). By focusing attention only on those with Grades II and III malnutrition, the obvious ones, we have been missing the opportunity to prevent a deterioration of those in Grade I, though it is easier and less time consuming to reverse this trend in early stages of malnutrition. To ensure more quality-time for community health workers' focus on the at-risk population, three alternative "high-risk" groups are proposed. Promotion of growth and weight change needs to be stressed more, instead of the nutritional status only in GMP programs. PMID- 8362301 TI - Smoking habits and attitudes among doctors in a Malaysian hospital. AB - A study of the smoking habits and attitudes toward smoking among 120 doctors at the Hospital Universiti Sains Malaysia was conducted between May to August 1991. Eighteen percent of the doctors were smokers, 13% ex-smokers and 69% had never smoked. All the smokers were male and all except one smoked only cigarettes. Three of the 32 female doctors were ex-smokers. Nineteen of the 21 smokers only smoked in areas where they could not be seen by the public. Most doctors (equally among smokers and non-smokers) had first-degree relatives (mostly males) who were smokers and 28% had relative with smoking-related disease. 81% non-smoking and 43% smoking doctors had advised healthy people to stop smoking. 92% non-smoking and 52% smoking doctors support the smoking-ban in the hospital. Seven of the 21 smokers had never attempted to quit smoking. PMID- 8362302 TI - Leprosy trends in northern Thailand: 1951-1990. AB - Data of new, previously untreated leprosy patients from 6 northern provinces of Thailand, diagnosed at McKean Rehabilitation Center, Chiang Mai and associated clinics between 1951 and 1990 were analysed. The following trends were found: 1) Decreasing numbers of new, previously untreated patients. 2) Increasing average age of patients at onset and presentation of disease. 3) Decreasing duration between onset and presentation. 4) Increasing percentage of patients presenting within the first year of symptoms. 5) Increasing percentage of paucibacillary cases. 6) Decreasing percentage of patients presenting with deformity. These trends are a reflection of those seen for the whole of Thailand and indicate that leprosy control is being effective. Patients are presenting at an earlier stage than before, with consequent reduction in disability and infectivity. Better usage of chemotherapy since 1976 has helped to reduce the transmission of bacilli from person to person, combined with effective health education activities which have dispelled some wrong ideas about leprosy and encouraged patients to seek help early in the course of the disease. Additional factors related to public health and living standards have also contributed. PMID- 8362303 TI - Impact of an educational program on the treatment practices of diarrheal diseases among pharmacists and drugsellers. AB - The impact of an intervention program, measured by changes in the prescription of ORS, antibiotics and antidiarrheal drugs by those pharmacists and drugsellers after administering the proposed educational package was assessed. The results of the study indicated that, before the educational program started, ORS was prescribed by pharmacists for 31.4% and 15.7% of watery diarrhea and dysentery episodes, respectively. Only 18.9% and 13.3% of drugsellers gave ORS to assessors in case of watery diarrhea and dysentery. Antibiotics and antidiarrheal agents were prescribed extensively, watery and dysenteric diarrhea (84% and 56% for watery diarrhea by pharmacists and drugsellers; 92% and 60% for dysentery). Antidiarrheal drugs were used as frequently. After the educational program, the assessment of the prescription behavior of the pharmacists showed no change in ORS, antibiotics and antidiarrheal drugs prescribed to treat watery diarrhea. In dysentery, the effective percent change in prescribing ORS between pre- and post- intervention program was much higher in intervention group than the control group. For drugsellers, effective percent change in ORS usage in treatment of watery diarrhea was 11.8% compared with -7.7% in the control group. No such change was observed in treatment of dysentery. There was a slight significant change in behavior concerning use of antibiotics among subjects getting information by mail, compared to those who got full intervention, when the pre intervention behavior, store type and treatment type was taken into account. PMID- 8362304 TI - Latrine use in rural Sarawak, Malaysia. AB - A cross-sectional survey covering 976 households in 41 rural villages covered by the Rural Health Improvement Scheme in Sarawak was carried out to determine the type of latrines they have and their usage of pourflush latrines. The survey was carried out by inspection and interview. Fifty-six percent of the households had pourflush latrines and upon inspection 91.3% of them showed signs of recent use. Based on the interview, ninety percent of the women responded that they always use the latrine for defecation. It was also reported that 86.5% of the husbands and 47.6% of the children below five years, always used the latrine for defecation. The most common reason for not using the latrine among adults was the lack of water to flush the latrines as well as not being home when the need arises. The reason for using the latrines were to keep the compound clean, convenience and health reasons. It is recommended that building latrines continue to be a prerequisite for getting water supply under the program and that non health-related reasons be emphasized in health education which aim to motivate people to build and use the latrines. PMID- 8362305 TI - Clinical trials with halofantrine in acute uncomplicated falciparum malaria in Thailand. AB - The antimalarial efficacy of halofantrine was compared with mefloquine in an open label, randomized comparative trial in adult male patients with acute uncomplicated falciparum malaria. Twenty-eight patients received halofantrine and 27 received mefloquine. Halofantrine was administered in 3 doses of 500 mg at 6 hour intervals and mefloquine was administered in divided doses of 1,250 mg or 1,500 mg depending on whether the patients weighed less than or more than 60 kg. The patients were followed for 42 days and observed for drug tolerance and evidence of recrudescence. Response to treatment was favorable with both drugs, but three patients (two treated with halofantrine and one with mefloquine) did not completely eliminate malaria parasites from peripheral blood films in seven days. The parasite and fever clearance times were 75.6 and 55.7 hours, and 80.1 and 61.3 hours, respectively for halofantrine and mefloquine. However, 12 patients recrudesced during the 42 day follow-up period. Nine of these had been treated with halofantrine and three with mefloquine. The 42-day cure rate for the two drugs was 56% and 84%, respectively. The side-effects of halofantrine and mefloquine were comparable and transient. These are diarrhea, dizziness, orthostatic hypotension and black out. However, vomiting was found to be more common in mefloquine group (41% vs 22%). PMID- 8362306 TI - Intramuscular artemether in female patients with uncomplicated falciparum malaria. AB - Thirty-three female patients suffering from acute uncomplicated falciparum malaria were treated with intramuscular artemether for 5 days during May-October 1990. Fourteen patients received 160 mg as an initial dose, followed by 80 mg daily for 4 days. Nineteen patients with low body weight (mean weight of 36.5 kg) were given artemether at 3.2/kg as a loading dose and followed by 1.6 mg/kg/dose for another 4 days. The geometric mean of parasitemia was 17,378/microliters (range 640-234,720). The mean fever (FCT) and parasite clearance time (PCT) were 41.8 and 49.4 hours, respectively. Two patients had probable intercurrent infection with FCT of over 7 days. Thirty-one patients had completed the 28-day follow-up. The cure rate was 90.3% (28/31). Three patients had RI type of response. Mild and transient adverse effects were experienced in eleven patients; these consisted of pain at the injection sites, vomiting, dizziness, abdominal pain, palpitation and diarrhea. These symptoms may in part be due to symptom complex of malaria. The MIC of chloroquine, quinine, quinidine and mefloquine was performed in all patients but only 25 isolates were successfully cultured and tested. The MIC of all tested drugs were shown to be higher than that of previous studies, suggesting that there is a rapid increase of mefloquine resistant strains of falciparum malaria. In conclusion, artemether proves to be effective against multiple drug resistant falciparum malaria (including mefloquine resistant strains) and can be considered as an alternative antimalarial to mefloquine. The drug was well tolerated in female patients with mild and transient side-effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362308 TI - The temperature--dependent expression of GST of Schistosoma japonicum (Philippine strain). AB - Obtained from pSj5, the cDNA gene encoding GST antigen of Schistosoma japonicum (Philippine strain) was ligated with efficient temperature-dependent PBV220 vector which was constructed in CAPM, and then introduced into host bacterium-DH5 alpha (E. coli) by transformation. Transformants were selected by ampicillin and recombinant clones were identified by restriction mapping. The result showed that recombinant clone 43 was the one carrying recombinant plasmid PBV 220 with the correct insertion of the gene fragment. The GST expression ability of clone 43 was investigated by GST enzymic activity assay and SDS-PAGE. A relatively high level of GST enzymic activity was expressed by this clone under the temperature dependent condition, that is, cultured at 30 degrees C and expressed at 42 degrees C. A more strongly stained 26 kDa protein band was identified by SDS PAGE. The result indicated that GST of S. japonicum (Philippine strain) could be expressed not only by IPTG induction, but also by the temperature-dependent method. PMID- 8362307 TI - Studies on chemotherapy of parasitic helminths: efficacy of artemether on Japanese strain of Schistosoma japonicum in mice. AB - Effects of artemether were examined on Schistosoma japonicum in mice. When the drug was given at a daily dosage of 200 mg/kg for 4 successive days from 46 days post-infection, a significant reduction in worm recovery was observed. A significant reduction in size of worms from the medicated mice was also seen compared with that from non-medicated controls. PMID- 8362309 TI - The antigenicity of GST antigen extracted from Chinese strain of Schistosoma japonicum. AB - The GST antigen, similar to Sj26 (Philippine strain), which plays an important role in inducing protective immunity against Schistosoma japonicum, can be extracted and purified from adult worms of the Chinese strain of S. japonicum. There are two bands at 26 kDa and 28 kDa of GST antigen called the 26-28 kDa GST antigen as identified by SDS-PAGE, and these have GST activities. Mice were immunized with the 26-28 kDa antigen and the specific antibody response in serum was assayed by ELISA, IFA and western blot. The antigenicity of the 26-28 kDa GST antigen in mice was significant. For example, the antigen could stimulate mice to increase the level of serum IgM and IgGl; the antibodies in serum of immunized mice could be localized in the antigenic determinants of tegument or body of the worms; specific antibodies against the antigens increased markedly after immunization as measured by ELISA or IFA; the antibody from mice immunized with the 26-28 kDa GST antigen can recognize 26-28 kDa antigenic molecules, identified by immunoblot assay. PMID- 8362310 TI - Comparative study on antigenicity and immunogenicity of 26-28 kDa antigen and recombinant Sj26 (RSj26) of Schistosoma japonicum. AB - This paper reports a comparison of the recombinant Sj26 (rSj26) antigen derived from the Philippine strain and the 26-28 kDa antigen isolated and purified from the Chinese strain of Schistosoma japonicum with respect to their antigenicity and immunogenicity. The results showed that there were obvious cross reactions between rSj26 and 26-28 kDa antigen when rSj26 antigen was tested against specific antibodies in sera of mice infected with the Chinese strain of S. japonicum or the 26-28 kDa antigen was tested against specific anti-rSj26 antibodies by ELISA, IFA and Western blotting. Both the 26-28 kDa and the rSj26 antigen had weak cross reactions with SEA antigen. The worm reduction rate after challenging with Chinese strain cercariae in mice immunized with rSj26 was 26 32%, similar to that in mice immunized with 26-28 kDa antigen. It is suggested that rSj26 antigen can induce a certain level of specific protective immunity in the host against infection by the Chinese strain of S. japonicum cercariae. PMID- 8362311 TI - The possibility of GST antigen from Chinese strain of Schistosoma japonicum for immunodiagnosis of schistosomiasis. AB - The GST antigen (called 26-28 kDa antigen) extracted and purified from Schistosoma japonicum adult worms was applied to the detection of specific antibodies in sera of infected mice and mice immunized with the above protein antigen by ELISA technique. The 26-28 kDa antigen was better than crude antigens (SEA, SWAP) when used to detect specific antibodies in sera from immunized mice. As with crude antigens (SEA and SWAP), the 26-28 kDa antigen could be used to detect specific antibodies in infected sera, with titers as high as 1:160-1:320. There were no false positive reactions and a positivity rate as high as that using SWAP occurred when the 26-28 kDa antigen was used in schistosomiasis patients and normal subjects by intradermal test. It is suggested that the 26-28 kDa antigen may be a suitable candidate for immunodiagnosis of schistosomiasis. PMID- 8362312 TI - The Hoeppli phenomenon in schistosomiasis japonica: historical findings and additional investigation in bovines. AB - The present paper deals with a buried knowledge of the early findings of the Hoeppli phenomenon in cattle infected with Schistosoma japonicum together with a revised list of bovines and other mammalian species in which this phenomenon has been found. It was noted that the percentage of the mature-egg granulomas with positive Hoeppli phenomena varied with the species of bovines, ie, higher positive percentage in the more susceptible cattle than in the less susceptible buffalos. The radiating filaments in fringes of the phenomenon were also stronger in cattle than in buffalos. PMID- 8362313 TI - Ivermectin in the treatment of bancroftian filarial infection in Orissa, India. AB - Ivermectin treatment was evaluated for its efficacy and side reactions in sixty patients of Orissa with Bancroftian filarial infection and microfilaremia. Ivermectin was administered as a single oral dose at four dosage levels (20, 50, 100 and 200 micrograms/kg), and both microfilarial clearance and associated side reactions were monitored in a double blind fashion. Blood microfilariae were cleared in all patients at all dosages within 1 to 14 days. In most patients microfilariae reappeared by third month. The microfilaria appearance by third and sixth month averaged 12.2 to 44 percent of pretreatment values in the four study groups. Side reactions were encountered in almost all patients, the commonest being fever, headache, weakness, myalgia and cough which occurred most prominently 12 to 72 hours after treatment. Side reactions were more frequent and severe in patients with high microfilaria counts. Clinical reaction scores for each group were independent of the dose administered. The 200 micrograms dose group showed significantly more rapid microfilariae clearance and its delayed reappearance as compared with the other dosage groups and without inducing significantly greater clinical reaction scores. PMID- 8362314 TI - Some epidemiological aspects of hookworm infection among the rural population of Bali, Indonesia. AB - Stool examination using direct smear method, Kato-Katz thick smear technique and modified Harada Mori test tube cultivation method were done on 2,331 people among the rural population of Bali. The serum ferritin was examined by ELISA technique and hemoglobin concentration by cyanmethemoglobin technique. Overall prevalence of hookworm infection was 24.02% with heterogeneity in local prevalences. The highest prevalence was found in wet highland area (46.3%), followed by wet lowland (27.7%), dry highland (14.2%) and dry lowland (10.9%). The majority of hookworm infection cases were associated with Ascaris and Trichuris infections. Most of the hookworm infections (73.3%) were light/very light in intensity with a mean EPG of 619. The prevalence and intensity of infection were increasing with age, and the age-prevalence and age-intensity curves were slightly convex. There was no significant difference of prevalence or intensity of infection between males and females. The condition and humidity of soil found to be an important determinant for prevalence of hook-worm infection. The frequency distribution of the intensity of hookworm infection showed an over-dispersed distribution pattern with 10% of people harboring more than 63% of parasite burden as measured by EPG. The prevalence of anemia was higher, but not statistically significant, in hookworm infected persons compared with people without infection. But this study failed to show a significant correlation between intensity of infection with hemoglobin level. There was a significant correlation between serum ferritin level with intensity of infection. PMID- 8362315 TI - Cryptococcal intracerebral mass lesions associated with cryptococcal meningitis. AB - 12 patients with cryptococcal intracerebral mass lesions associated with cryptococcal meningitis are reported. There were 6 males and 6 females with a mean age of 41 years. Most of them presented with symptoms and signs of meningitis initially without focal neurological signs. Computed tomography revealed single or multiple, well or poorly marginated hypodense lesions without perilesional edema, except 1 case which had marked edema, with or without ring enhancement. One case had small hyperdense, diffuse, enhanced nodules. New lesions or progression of the existing lesions occurred during medical therapy in some patients. The clinical manifestations of patients with intracranial mass lesions did not significantly differ from patients without mass lesions, but the mortality was higher (50% vs 29%). PMID- 8362316 TI - Acute injuries to cervical joints. An autopsy study of neck sprain. AB - A comparative study of cervical spines from 16 subjects who died of major trauma and 16 control subjects who died of natural causes, showed clefts in the cartilage plates of the intervertebral discs in 15 of 16 spines from the trauma victims. These were quite distinct from the uncovertebral clefts and central disc fissures that are a normal feature of aging in cervical discs. Posterior disc herniation through a damaged anulus fibrosus and hemarthrosis in facet joints were also observed. No directly comparable lesions were found in the control subjects, but two discs in this group showed "rim lesions," which may be old injuries. Disc lesions are common in injured cervical spines where translation is much greater than in the lumbar spine and these lesions are slow to heal. It is suggested that such injuries could cause the pain experienced by patients with neck sprain. PMID- 8362317 TI - An early comparative analysis of the use of fibular allograft versus autologous iliac crest graft for interbody fusion after anterior cervical discectomy. AB - During a 2-year period (1988-1989), 23 cases of anterior cervical discectomy were performed with cadaveric fibular allograft instead of autologous iliac crest graft. The mean age of the patients was 35 years. There were 10 men and 13 women. In most cases, a one-level fusion was performed at the C5-6 level. The Smith Robinson technique was used for discectomy and fusion, for both one- and two level fusions. Evidence of radiographic fusion was achieved in 92% of the cases. Twenty-five cases of anterior cervical discectomy in which autologous iliac crest graft was used (1987-1988) were examined retrospectively for comparison. The mean duration of hospital stay was less in the allograft group (5.4 days vs. 7.25 days). In addition, postoperative pain was less in the allograft group because the allograft group did not have pain from the donor site. In conclusion, the use of fibular allograft for interbody fusion after anterior cervical discectomy can be performed with acceptable rates of fusion and less postoperative pain, as compared to the use of autologous iliac crest graft. PMID- 8362318 TI - Use of sciatic neurogenic motor evoked potentials versus spinal potentials to predict early-onset neurologic deficits when intervention is still possible during overdistraction. AB - Spinal evoked potentials, sciatic neurogenic motor evoked potentials, and somatosensory evoked potentials were recorded before and after overdistraction of the spinal cord, and compared with the clinical status of 14 pigs. The sciatic neurogenic motor evoked potential consisted of two components: fast and slow. The fast component was more sensitive and associated to a greater degree with motor function in wake-up tests than the slow component somatosensory evoked potential and spinal evoked potential. Furthermore, the loss of only the fast component in the initial status allowed the possibility of improvement of motor activity in the final wake-up test. The peripheral neurogenic motor evoked potentials recording yielded more information about spinal cord function: motor and sensory. The current study suggests that a peripheral response is a better index to the onset of overdistraction and to the efficiency of intervention, when the neurologic deficit after overdistraction of the spine is reversible. PMID- 8362319 TI - Correlation between histopathologic features and magnetic resonance images of spinal cord lesions. AB - The authors report a correlation between histopathologic features and magnetic resonance images of spinal cord lesions in 19 human spinal cords with various types of lesions. Abnormally high T2-weighted image signal intensities appeared nonspecifically in mildly altered lesions or areas with edema. In the gray matter, a low T1-weighted image in addition to a high T2-weighted image signal intensity appeared in severely altered lesions with necrosis, myelomalacia, or spongiform change. In the white matter, abnormally high T1-weighted image intensities appeared in severely altered lesions. Based on these preliminary results, it appears that a correlation between the degree of histopathologic alteration of the spinal cord and magnetic resonance images in clinical cases can be made. This is the first study to clarify the correlation between histopathologic features and magnetic resonance images of the diseased human spinal cord. PMID- 8362320 TI - Study of distribution and characteristics of spinal disorders using a validated questionnaire in a group of male subjects not exposed to occupational spinal risk factors. AB - This article presents the content and the application criteria of a questionnaire intended for the study of spinal disorders in workers and the results of an investigation, carried out via this questionnaire, in a group of 1205 male workers not exposed to occupational risks for the spine either currently or in the past. The data, stratified into three age classes (26-35, 36-45, and 46-55 years) concern: cases of disc herniation, cases of acute lumbago, subjects with spinal disorders in the period before the last 12 months. In addition, for each spinal segment (cervical, thoracic, and lumbar) data are reported on cases classified as positive according to predefined criteria, cases with disorders of any degree, disability caused by disorders, absence from work, and recourse to treatment for disorders. These data constitute a reference for cross-sectional epidemiologic studies on the diffusion and features of spinal disorders in workers exposed to occupational risks for the spine, performed using the same questionnaire. The authors discuss selection criteria and criteria for use of the data in inferential analysis for the purposes of producing correct assumptions on the causal relationships between occupational risk and spinal disorders. PMID- 8362321 TI - The variable screw placement spinal fixation system. Report of a prospective study of 250 patients enrolled in Food and Drug Administration clinical trials. AB - The variable screw placement (VSP) system uses transpedicular screws and slotted plates to achieve constrained segmental fixation of the spine. A prospective multicenter study of 250 patients was performed under a Food and Drug Administration approved protocol to test the safety and effectiveness of this system. Complete 2-year follow-up data are reported for 169 of 223 (73%) patients who had fixation of three spinal levels or fewer. "Clinical success" was defined as an excellent or good result or improvement of two grades in a 10-point combined pain and function scale. "Fusion success" was defined by presence of continuous trabecular bone bridging the fusion area. For 86 patients with postsurgical failed back syndrome, clinical success was achieved in 69 (80.2%) and fusion success in 76 of 83 (91.6%) patients. These success rates were statistically higher than previous literature reports (P = 0.01 for clinical success and P = 0.02 for fusion success). For spondylolisthesis, clinical success was achieved in 44 of 57 patients (86.3%) and fusion success in 43 of 47 (91.5%) patients. For spinal stenosis, clinical success was achieved in 25 of 32 patients (78.1%) and fusion success in 30 of 31 (96.8%) patients. Overall fusion success was achieved in 186 of 200 (93%) patients with no statistical difference when comparing the numbers of levels fused. There were 21 device-related complications (8.4%) and 16 non-device-related complications (6.4%). PMID- 8362322 TI - New methods of measuring vertebral rotation from computed tomographic scans. An intraobserver and interobserver study on girls with scoliosis. AB - The purpose of this study was to search for constant and reliable reference points on the computed tomographic scans of scoliotic spines to measure vertebral rotation. Several methods using different sets of reference points on computed tomographic scans were tested for reliability. Two methods that gave minimum variation between the readings are presented here with interobserver and intraobserver reliability on 17 girls with adolescent idiopathic scoliosis. The selection of reference points for the two methods were as follows: In method 1, the vertebral rotation was an angle formed by two lines; one, a line joining the junction of the inner surfaces of two laminae and the midpoint of the posterior surface of the vertebral body and second, the vertical plane of the computed tomographic machine. In method 2, three datum points were marked; one at the junction of the inner surfaces of the laminae, and the other, one each at the junction of the inner surfaces of the lamina and the pedicle. A line bisecting this angle is drawn by the computer and the vertebral rotation was an angle between this line and the vertical plane. The 95% confidence intervals of these two methods for intraobserver variation were between 1.2 to 4.4 degrees. There was no significant difference between the readings obtained by each observer except on three occasions for observer 1. When these methods were tested for interobserver reliability, method 1 showed significant statistical differences between the readings obtained by the two observers. However, the readings obtained using method 2 were not significantly different between the two observers (95% confidence intervals = 3.2 to 5.8 degrees).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362323 TI - Three-dimensional head axis of rotation during tracking movements. A tool for assessing neck neuromechanical function. AB - The purpose of this article is to report normal variation in the screw (helical) axis of rotation of the head during various types of natural tracking movements. Nine normal subjects and eighteen subjects with neck injury faced a grid of targets separated by 10-degree intervals, and were instructed to use a head pointer (laser) to track whatever target was lit. Various horizontal, vertical, and oblique target sequences were employed. The normal subjects exhibited several consistent trends in finite screw axis parameter variation: vertical movements have a laterally-directed axis whose midsagittal plane crossing position is a function of the head orientation (typical range C3-T1); oblique movements have a diagonally-directed axis and an even greater orientation-specific range (C1-T1); and horizontal movements have a vertical axis that is modified near horizontal orientation extremes and is asymmetrically influenced by upward and downward bias orientations. Subjects with neck injury were seen to exhibit a variety of abnormal screw axis patterns. PMID- 8362324 TI - Can lumbar spine radiographs accurately determine fusion in postoperative patients? Correlation of routine radiographs with a second surgical look at lumbar fusions. AB - Controversy centers on the determination of surgical fusion in lumbar spinal patients. What method best determines the nature of surgical arthrodesis remains unanswered. Numerous studies have investigated the accuracy of different radiologic tests. Although the best method has not been determined, plain radiography is certainly the most widely used in many centers and reported in scientific articles. In most of the literature a poor agreement between radiographic interpretation and surgical findings was observed. The main reasons seemed to be the lack of an accurate method to assess the radiographs. The authors rely on a radiologist or spinal surgeon to estimate the success of bony fusion by reviewing a two-dimensional radiograph. The purpose of this study was to determine the accuracy of plain radiographs to predict the presence of a surgical fusion. Forty-nine patients underwent fusion site exploration in the course of hardware removal. All patients had a one- or two-level posterolateral fusion and posterior lumbar interbody fusion with pedicle screw/link rod instrumentation. Immediate preoperative anteroposterior and lateral radiographs were taken before hardware removal that included both visual assessment and a Kocher mechanical test. Two spinal surgeons and two musculoskeletal radiologists blindly judged the preoperative radiographs as to the absolute presence or absence of successful arthrodesis. A second review was repeated at 3 months. The overall agreement between radiographic assessment and actual surgical findings was 69%. The range among observers was 57-77%. The overall false positive rate was 42% (0-75%), while the false-negative rate was 29% (20-51%). Success of observed surgical arthrodesis at the time of the second look was 90% and this number was used as the standard in the agreement process. In comparing the radiographic observations with the surgical findings it is suggested that in one of five cases the plain radiographs underestimate the degree of fusion. This finding agrees with the authors' knowledge of osteoid and mineralized bone. The premineralized osteoid may be functionally fused, but appear radiolucent on radiographic film. Once solid trabecular bony bridging occurs radiographic identification of fusion is easier to determine. PMID- 8362325 TI - Roentgenographic evaluation of thinning of the lumbar pedicles. PMID- 8362326 TI - The etiology of focal spinal arachnoiditis. An experimental study. AB - Focal arachnoiditis and back pain have been attributed to potentially irritating substances leaking into the spinal canal from the lumbar intervertebral disc or facet joints. Through experimentation this hypothesis was tested: the nucleus pulposus (escaping from the intervertebral disc), lactic acid (from anaerobic glycolysis in the disc), chondroitin sulfate (a component of glycosaminoglycans in the disc), or synovial fluid (from degenerating facet joints) causes inflammation in the meninges if it contacts the dura mater. The test and control substances were injected into the epidural space of monkeys. Twelve weeks later the animals were killed; the dural sac was exposed by total lumbar laminectomy, grossly inspected, and then removed, fixed, sectioned, stained, and examined microscopically. Nucleus pulposus produced significant fibrosus in the arachnoid and epidural spaces; the other substances did not cause fibrosus or inflammation. The study suggests that leakage of nucleus pulposus into the epidural space causes an inflammatory response in the arachnoid and epidural spaces. PMID- 8362327 TI - Cross-sectional study of the isokinetic muscle trunk strength among school children. AB - Our surveys have shown lifetime prevalence of L.BP. over 30% among schoolchildren. The purpose of this study was to evaluate the relationship between back and isokinetic trunk strength, anthropometric parameters, and sports activities. One hundred and seventeen healthy children aged 10-16 years were included. All these volunteers had semi-structured interview, anthropometric and dynamic strength measurements. Lifetime prevalence of back pain was 44.5% and point prevalence was 13%. In this cross-sectional study, anthropometric and strength profiles were significantly related to age and gender. Non specific low back pain was not correlated to trunk muscle strength and/or sports activities. PMID- 8362328 TI - Forces exerted during spinal manipulative therapy. AB - Spinal manipulative therapy has been widely recognized in the medical fields as a conservative treatment modality for spinal dysfunction and pain. Spinal manipulative therapy consists of an application of a thrusting force on a specific part of the spine in a well-defined direction. The magnitude of this force has been associated with positive treatment effects, such as realigning vertebral bodies, mobilizing spinal joints, relaxing back musculature through reflex pathways, and producing a respiratory burst. However, direct force measurements during spinal manipulative therapy in a clinically relevant situation have not been performed to date. The purpose of this study was to measure the forces exerted onto patients during spinal manipulative therapy on various locations of the spinal column. Force measurements were obtained using a thin, flexible pressure mat. The results indicate that peak and preload forces are considerably smaller for spinal manipulative therapy performed on the cervical spine compared to corresponding values obtained on the thoracic spine and sacroiliac joint. Furthermore, for treatments on the thoracic spine and sacroiliac joint, a significant relation was found to exist between preload and peak forces. PMID- 8362329 TI - Compression strength of donor bone for posterior lumbar interbody fusion. AB - Forty-three blocks of allograft bone used clinically for posterior lumbar interbody fusion and twenty-three blocks of xenograft bone from goats and cows were tested in compression and compared with the clinical mechanical requirements of posterior lumbar interbody fusion. Variations in processing methods allowed evaluation of the effects of processing on mechanical strength. Fresh-frozen cancellous bone from Os Bone (Cleveland, OH) failed at an average load of 863 +/- 615 N. Fresh-frozen cancellous bone from the Mid American Tissue Center (Massilon, OH) failed at an average load of 3492 +/- 1720 N. Freeze-dried cancellous bone obtained from the American Red Cross failed at an average load of 1595 +/- 1031 N. Air-dried ethylene oxide sterilized cancellous bone from Os Bone failed at an average load of 1338 +/- 691 N. Air-dried ethylene oxide sterilized cancellous bone from Mid America failed at an average load of 1616 +/- 1157 N. Fresh-frozen tricortical bone from Mid America failed at an average load of 2257 +/- 1081 N. Air-dried ethylene oxide sterilized tricortical bone from Os Bone failed at an average load of 2474 +/- 1928 N. Air-dried ethylene oxide sterilized tricortical bone from Mid America failed at an average load of 2308 +/- 422 N. Bovine Surgibone from Unilab (Hillside, NJ) failed at an average load of 2967 +/- 399 N. Strength of bone in compression was not weakened by freeze drying, air drying, ethylene oxide sterilization, or by incubation at 37 degrees C for 1 week before testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362330 TI - Bilateral pedicular stress fractures after successful posterior spinal fusion for adult idiopathic scoliosis. AB - A patient with adult idiopathic scoliosis who was successfully treated with posterior spinal fusion with segmental instrumentation from T3 to L4 is presented. One year after surgery fractures of both L4 pedicles developed, which were managed nonoperatively. Clinical union was achieved in 2 months and the patient was followed with serial computed tomographic scans to confirm union. A review of the current literature is also presented. PMID- 8362331 TI - Central retinal artery occlusion after scoliosis surgery with a horseshoe headrest. Case report and literature review. AB - Central retinal artery occlusion is a well-documented entity that occurs after trauma and embolic, thrombotic, or spasmodic episodes in both children and adults. Its occurrence as a complication of elective surgery is very rare but quite tragic. This report describes a case of central retinal artery occlusion occurring in a child after scoliosis surgery in which a horseshoe headrest was used. Recommendations are given on how to avoid this serious complication. PMID- 8362332 TI - Lumbosacral agenesis. Three cases of reconstruction using Cotrel-Dubousset or L rod instrumentation. AB - Three patients with lumbosacral agenesis underwent surgery to lock the lumbopelvic instability. All three patients had an unstable sitting position and a kyphotic bearing that impaired intestinal transit or hampered further colostomy or ureterostomy. Luque instrumentation with iliac fixation performed according to Galveston was used in one patient. Cotrel-Dubousset instrumentation was used for the two other patients. Autografts plus allografts provided sufficient bone for fusion without requiring lower leg amputations. Increased hip flexion was obtained after pelvic stabilization, but knee flexion contracture remained the same. All patients showed improved intestinal transit or decreased urinary infections, and two patients attained a stable sitting position without aid. PMID- 8362333 TI - Delayed post-traumatic vertebral collapse (Kummell's disease): case report with serial radiographs, computed tomographic scans, and bone scans. AB - A case of delayed posttraumatic vertebral collapse (Kummell's disease) is described and documented with serial radiographs, computed tomographic scans, and bone scans. The bone scan was normal before the back injury occurred and showed increased radionuclide uptake 3 weeks after injury and before vertebral collapse. Plain radiographs and computed tomographic scans taken during the interval between injury and collapse revealed no evidence of fracture or bone destruction. The authors believe this represents the first example of Kummell's phenomenon documented with serial computed tomographic and bone scans, and provides further support to the ischemic necrosis theory as the underlying process. PMID- 8362334 TI - A case-control study of risk factors for industrial low back injury. The utility of preplacement screening in defining high-risk groups. AB - Using a cohort of 8183 postal workers, this study assesses the efficacy of preplacement medical examinations in defining the risk of occupational low back injuries. From this cohort, 154 subjects with occupational low back injuries between 1983 and 1988 and 942 control subjects who did not have low back injuries were identified. A multivariate logistic regression shows that a history of prior disability, odds ratio 2.90 (95% confidence interval 1.88-4.48), and a heavy lifting job, odds ratio 1.91 (1.32-276) are associated with occupational low back injuries. However, a history of previous back injury on screening examination is not associated with subsequent occupational injury. The association between a history of disability and occupational low back injury has not been previously noted and warrants further research. PMID- 8362335 TI - When pharmacologic anesthesia is precluded: the value of hypnosis as a sole anesthetic agent in dentistry. AB - Occasionally, a dental patient presents his/her dentist with a history of hypersensitivity to local anesthetic agents. The symptoms may include immediate reactions to the injection procedure (dizziness, shortness of breath, tachycardia, etc), or delayed reactions to the anesthetic (swelling, urticaria, etc). Although the true incidence of local anesthetic allergy is low, such a history often involves the patient's anxiety regarding the use of the drug in question, and the dentist's apprehension to treat the "problematic" patient. In such cases, hypnosis can play a major role in controlling pain and the associated distress. In the present article, the method concerning the implementation of hypnosis to induce local anesthesia is described and illustrated through case demonstrations. PMID- 8362336 TI - Cohort differences among aging populations: a challenge for the dental profession. AB - The pattern of utilization of oral health services by older adults is changing as more older people maintain their natural teeth. Heterogenicity among persons aged 65 and older is probably greater than in any other period in the life cycle; however, all too often, all age groups over age 65 have been grouped together for program planning or data analysis. The socio-dental and historical influences on five specific age cohorts born between 1905 and 1945 are presented so that dentists may better understand the differences in attitudes and expectations of these individuals when they seek treatment. PMID- 8362337 TI - A suggested curriculum for teaching conscious sedation in advanced general practice programs: GPR and AEGD. American Association of Hospital Dentists. AB - Previously published national guidelines related to the teaching and performance of conscious sedation in dentistry have not included guidance in this area for program directors of General Practice Residency and Advanced Education in General Dentistry Programs. A suggested curriculum is presented here for use by program directors of such programs who wish to design training experiences in their own programs or as a reference for program directors who wish to compare their programs with experiences provided in other locations. Guidelines are provided for facilities, equipment, personnel, records and preparation necessary to perform conscious sedation procedures, as well as goals, objectives, and evaluation methodology for training residents in conscious sedation. PMID- 8362338 TI - Identification of appropriate outcomes for an aging population. AB - Outcome measures are necessary for assessment of the appropriateness, quality, necessity for, and effectiveness of oral health care. With the growing number of older adults in the United States, it is appropriate to reflect on the unique characteristics of this segment of our society and how these characteristics may influence the identification of appropriate outcome measures. Older people often demonstrate multiple acute or chronic oral diseases with interrelated symptoms and clinical findings. Older persons are more likely to take medications with potentially adverse oral health effects. Patients experience a variety of disease processes over many years and have variable access to and experiences with the dental care system. These characteristics make the selection and interpretation of outcomes complex. Limitations of existing measures and considerations for the development of new outcomes measures specifically for older populations are reviewed. PMID- 8362339 TI - AIDS education and training centers (AETCs) as resources. PMID- 8362340 TI - An evaluation of the effectiveness of four mechanical plaque-removal devices when used by a trained care-provider. AB - Many care-dependent elderly individuals live in nursing homes and must depend on nursing home aides for oral hygiene care. It is generally agreed that the level of oral hygiene care among care-dependent nursing home residents is less than optimal. Two reasons are time constraints and the difficulty involved in brushing other individuals' teeth. The identification of effective and efficient plaque removal devices for use by care-providers should make it easier for nursing home aides to incorporate effective oral hygiene care into their daily routines. This pilot study was undertaken to determine the relative effectiveness of four plaque removal devices with different basic designs when used by a non-professional care provider on 10 healthy volunteers. A brush with curved bristles on the lateral aspect of the brush head and short straight bristles in the center (Collis-curve) and an electric toothbrush with tufts that rotate reciprocally (Interplak) were the most effective, a conventional brush (Oral-B) was somewhat less effective, and a disposable foam brush (Abco) was least effective and similar to the prebrushing plaque score (baseline). All the volunteers reported that the Collis curve was the most comfortable brush, and the care-provider reported that it was the easiest to use. PMID- 8362341 TI - Normal and atopic IgE responses. PMID- 8362342 TI - Leukotriene antagonists and inhibitors as modulators of IgE-mediated reactions. PMID- 8362343 TI - Regulation of IgE synthesis: from the membrane to the genes. PMID- 8362344 TI - Can anti-IgE be used to treat allergy? AB - A summary of the properties of CGP 51901 is shown in Table 3. On the basis of its binding to IgE and IgE-secreting cells and its activity in vitro and in vivo, CGP 51901 is expected to be able to decrease serum IgE by direct clearance of IgE and by reduction of the numbers and productivity of IgE-secreting cells. The end result of reduction of IgE in the circulation and on mast cells is expected to be the attenuation of IgE-mediated reactions and the improvement in allergy symptoms. The effective serum concentration of CGP 51901 is expected to be in the range 1-10 micrograms/ml. Because CGP 51901 is an antibody specific for IgE, it is expected to be highly selective in its activity. Because IgE does not appear to be essential and because CGP 51901 has been rigorously tested to confirm its non-anaphylactic nature, this treatment is not expected to have any adverse effects. Therefore, CGP 51901 is expected to be safe and to have a good probability of being effective when it is tested in human clinical trials. PMID- 8362346 TI - Transpedicular decompression and stabilization of burst fractures of the lumbar spine. AB - Twenty-seven consecutive patients with neurological impairment due to burst fractures of the lumbar spine were operated upon, via the postero-lateral route, over a 38-month-period. Transpedicular fixation devices [posterior segmental fixator (PSF) or variable screw placement system (VSP)] were applied in all cases, in order to achieve short-segment fusion of the fractured spinal segment. Return to useful motor power or neurological normality (median follow-up: 18.7 months) occurred in 22 cases (81% of the whole series), with this outcome resulting in all but one of the cases with preoperative incomplete neurological deficit. Postoperative encroachment of the spinal canal, degree of kyphotic deformity, and reduction of the vertebral height showed statistically significant differences compared with the corresponding preoperative values. PMID- 8362347 TI - The gravitational shunt: an alternative approach to cerebrospinal fluid shunting. AB - Current cerebrospinal fluid shunts use complex differential pressure values to regulate drainage. Such systems are prone to overdrainage and obstruction, and thus have an unpredictable effect on intracranial pressure (ICP). The gravitational shunt (GS) introduces an alternative approach. It uses a single, simple valve to balance the pressures generated within a vertical shunt system. The ICP is then regulated by the position of the valve along the cranioabdominal shunt axis and not by the mechanical properties of the valve. Bench testing demonstrated that when using the GS (1) a linear correlation (r = 0.91, p < 0.001) exists between the ICP and the position of the valve along the vertical shunt axis, (2) positive and negative ICPs are maintained, and (3) the ICP can be predicted by an equation derived from theoretical principles. The GS uses a single, simple valve as a pressure regulator and an antisiphon device. It allows the maintenance of a normal negative ICP in the upright position without risk of over-drainage. The other benefits of this system are discussed. PMID- 8362345 TI - Adhesion molecules in a primate model of allergic asthma: clinical implications for respiratory care. PMID- 8362348 TI - Hydrocephalus: slit ventricles, shunt obstructions, and third ventricle shunts: a clinical study. AB - In a retrospective 5 year study of patients with ventricle shunts for hydrocephalus (N = 88), studies were developed on slit ventricles in teenagers and in young adults. These studies presented here are (1) time to slit ventricles from first shunt and average upright ICP associated (N = 24); (2) upright ICP in asymptomatic long-term ventricle shunt patients without slit ventricles (N = 21), (3) clinical course of patients with uncorrected slit ventricles and lateral ventricles or third ventricle shunts (N = 31), (4) resolution of slit ventricles by Zero ICP Shunt with normal upright ICP (N = 28), (5) no resolution of slit or large ventricles in shunted patients with normal upright ICP (N = 23), and (6) unreliability of CT ventricle size (slit or enlarged) after normal upright ICP achieved (N = 28; 23). Surprisingly, slit ventricle patients with the ventricular catheter in collapsed lateral ventricles develop shunt obstruction within 20 months (21/31; 71%; 10/31 29%) patients with ventricle catheters incidentally in the third ventricle did not obstruct during the 4 1/2 year follow-up. PMID- 8362349 TI - Long-term outcome in surgically treated encephalocele. AB - This report describes long-term operative outcome of 24 cases with occipital encephalocele. The follow-up periods are between 4 and 20 years. Of the 24 patients with occipital encephalocele, two have died. Of the 22 living patients, 16 are living without neurological deficit, while six are disabled mentally and/or physically. Four cases of encephalocele developed hydrocephalus, and two of them died while the other two are still living with severe handicap. The presence of gross brain tissue in the sac of encephalocele and the size of the sac were also unfavorable factors for the prognosis. We conclude that the size and the content of the sac and associated hydrocephalus are the important factors that influence the long-term prognosis of occipital encephalocele. PMID- 8362350 TI - Giant aneurysm of internal carotid artery in a four-year-old child: a case report. AB - A case of giant saccular aneurysm in early childhood is reported. An internal carotid aneurysm presenting with episodic headache was successfully clipped with complete relief of symptoms. The patient was also investigated for a possible collagen deficiency which proved negative. Clinical features and pathogenesis of this rare lesion are discussed. PMID- 8362351 TI - Discrepancy between provocative test and clinical results following endovascular obliteration of spinal arteriovenous malformation. AB - We report a case of spinal arteriovenous malformation with no signs of neurological deterioration after transarterial embolization, although the results of a provocative test with injection of lidocaine was positive on monitoring of clinical findings and somatosensory-evoked potentials (SEPs). We discussed the possible overestimation by the provocative test, and the limitations of SEP monitoring during endovascular surgery. PMID- 8362353 TI - Multifocal giant cell glioblastoma: case report. AB - Glioblastoma multiforme (GM) of the cerebellum is a rare tumour. A variant of GM, a multifocal giant cell glioblastoma, initially presenting in the cerebellum, has not previously been reported. A giant cell glioblastoma occurring in a 46-year old man who presented initially with a cerebellar tumour is described. One month after excision of the tumour, the patient had a grand mal seizure. Computed tomography (CT) showed a low-density lesion in the left temporal lobe. Four months later he developed dysphasia and right-sided hemiparesis. Repeat CT scan revealed a large temporal lobe tumour which was excised, and histologically found to be a giant-cell glioblastoma with histopathological similarities to the original cerebellar tumour. The clinical course, computed tomographic and pathological features of this tumour are described and discussed. PMID- 8362352 TI - Suprasellar embryonal carcinoma which developed ten years after local radiation therapy for pineal germinoma. AB - We recently encountered a case of suprasellar embryonal carcinoma which developed 10 years after local radiation therapy for pineal germinoma. This 29-year-old male was admitted because of abnormal behavior, disturbed consciousness, and increased intracranial pressure. Computed tomography and magnetic resonance imaging disclosed a tumor spreading from the suprasellar region to the third ventricle and the anterior horn of the left lateral ventricle, accompanied by fresh hemorrhage within the tumor. He underwent subtotal removal of the tumor, followed by chemotherapy with cisplatin and etoposide. The tumor was histologically rated as embryonal carcinoma with differentiation into yolk sac tumor and choriocarcinoma. PMID- 8362354 TI - Cerebral revascularization with an artificial graft: long-term follow-up and discussion of the role of graft pretreatment with modified host endothelial cells. AB - Controversy remains regarding the effectiveness of EC/IC bypass for the prevention of stroke and the authors believe that some studies suggest that a subcategory of patients disabled by transient flow-related symptoms may benefit from surgery. The authors present a 7 1/2 year follow-up analysis of a patient who had undergone an EC/IC bypass from the proximal extracranial carotid to the middle cerebral artery using a 4 mm Gore-Tex prosthesis. Following his death from pulmonary sepsis, the graft was retrieved. Pathological and electron microscopic findings are reviewed. PMID- 8362355 TI - Paroxysmal bilateral dysosmia treated by resection of the olfactory bulbs. AB - Dysosmia, or the distortion of olfaction, is most commonly preceded by viral illness or head trauma, but has a variety of etiologies. The precise nature of the disease process remains obscure. Medical management is largely empiric, and has been aimed at treating underlying illnesses, restricting triggering medications, as well as various pharmacologic interventions. Successful eradication of a severe case of persistent unilateral paroxysmal dysosmia with resection of the ipsilateral olfactory bulb has been reported. We report here a case of bilateral paroxysmal dysosmia, refractory to medical therapy, successfully treated with bilateral olfactory bulb resection. PMID- 8362356 TI - Anastomosis of occipital artery to anterior inferior cerebellar artery with interposition of superficial temporal artery. Case report. AB - A 56-year-old man with vertebrobasilar insufficiency and associated findings including quadriparesis, dysarthria, cerebellar ataxia, nystagmus, and somnolence underwent left occipital artery (OA) to anterior inferior cerebellar artery (AICA) anastomosis with interposition of a superficial temporal artery (STA) graft. This procedure was chosen because cerebral angiograms demonstrated occlusion of the right vertebral artery (V3) and severe stenosis of the V4 segment of the left vertebral artery, with perfusion of the territory of the left posterior inferior cerebellar artery via the ipsilateral AICA, and because dissection of the OA is a relatively difficult and time-consuming procedure. Dissection of the STA, on the other hand, is much easier. Preoperative measurements of local cerebral blood flow in the vertebrobasilar circulation before and after intravenous administration of acetazolamide (500 mg) were obtained, and demonstrated low flow and hemodynamic compromise in the posterior circulation. The patient's hemodynamic and neurological status improved following surgery. In this report, we present a new and simplified method of OA-AICA anastomosis with interposition of STA graft. PMID- 8362357 TI - Terms describing brain ischemia by tempo are no longer useful: a polemic (with apologies to Shakespeare). PMID- 8362358 TI - Selective peripheral denervation for spasmodic torticollis: surgical technique, results, and observations in 260 cases. AB - A total of 260 cases of spasmodic torticollis or of the cervical component of diffuse dystonias have been surgically treated with selective peripheral denervation of the involved muscles sparing their antagonists, after verification with electromyography and, if necessary, nerve blocks. Total or marked relief of symptoms with preservation of normal or nearly normal movements has been obtained in 88% of the patients with surgery followed by early physiotherapy. There are minimal sequelae with this approach. Selective denervation may be recommended if, after 2 years, conservative treatment, including botulinum injections, does not offer satisfactory relief of symptoms. PMID- 8362359 TI - Tissue formation on cementum surfaces in vivo. AB - The purpose of the present investigation was to study cell colonization of and tissue formation on denuded (anorganic) cementum surfaces as well as denuded demineralized cementum surfaces. The most conspicuous finding was the distinctly different pattern of cell colonization and subsequent tissue formation on etched and non-etched denuded cementum surfaces. Non-etched cementum surfaces displayed a limited number of resorbing cells and resorption lacunae, while etched cementum surfaces displayed an abundance of fibroblast-like cells in varying stages of activity in a meshwork of fibres, probably collagenous. These fibres were organized in a layer parallel to the root surface. This appearance of a fibrous capsule-like structure has previously been associated with periodontal healing with a non-functional repair-tissue. It may be concluded, based on the present results that, a cementum surface in which collagen fibers have been exposed presents a suitable surface for colonization by mesenchymal cells. However, if collagen fibers are not exposed in the cementum surface leaving mineralized surface, mesenchymal cells appear not to be able to attach. PMID- 8362361 TI - Changes in comprehensive dental care of the primary dentition from 1979 to 1989. II. Restorative treatment of primary molars in a population treated at a university dental clinic. AB - The aim of this study was to compare the success of operative caries therapy of primary molars in two cohorts, one of children born in 1971, Cohort '71, and the other of children born in 1981, Cohort '81, followed up from the age of 3 to 8 years. There were significantly fewer caries lesions to treat in Cohort '81 than in Cohort '71. In Cohort '71, silver amalgam was used while in Cohort '81 silver amalgam was inserted in 65% and glass polyalkeonate cement (GPA) in 35%. Significantly fewer restorations were replaced in Cohort '81 than in Cohort 71, 49 v. 106. When the proportion of replacements was studied in relation to the number of proximal caries lesions, the percentage of replacements in Cohort '71 was 17% and in Cohort '81 14%, the distal surface of the lower first molar showing the same proportion in both cohorts, 21%. Of all replacements in Cohort '81, 41% were performed in the high caries prevalence group. In Cohort '81, 22% of all silver amalgam and 6% of all GPA fillings were replaced. The number of extracted primary molars decreased significantly, from 4% in Cohort '71 to 2% in Cohort '81. The success rate of the operative caries therapy did not increase much. Instead, cost benefits were found in decreasing caries prevalence and later onset of manifest caries. PMID- 8362360 TI - Vertical forces developed by the jaw elevator muscles during unilateral maximal clenching and their distribution on teeth and condyles. AB - The activity of the jaw elevator muscles (EMG) was recorded during maximal clenching in ICP and unilaterally on 2nd and 1st molars, premolars, canines and central incisors in ten subjects with complete dentitions, normal occlusal relationships, and without signs and symptoms of craniomandibular disorders. The EMG activities were converted to relative muscle force. The distribution of this relative muscle force on teeth and condyles was then calculated by means of a three-dimensional mathematical model. The results suggest that the magnitude of the muscle force is strongly associated with the localization of the biting point. Thus the greatest muscle force is produced during clenching in the intercuspal position (100%). At unilateral clenching 75% of this ICP-force is reached during rubber pad clenching on 2nd molars, 85% during rubber pad clenching on 1st molars and 45% during clenching on incisors. The calculations of the mathematical model showed then that highest bite force should be produced on 2nd molars (55% of the muscle force produced in ICP-clenching) and lowest on incisors (20%). Highest condylar load should be found on non-biting side condyles (20% of the muscle force produced in ICP-clenching) and lowest on biting side condyles (0%). PMID- 8362362 TI - Changes in oral status and dental treatment in long term hospital inmates in Stockholm from 1988 to 1990. AB - The proportion of elderly in the Swedish population is increasing. In future elderly people will have retained more teeth and will require higher standards of dental care as long as they are healthy. There is an increasing trend towards admission of only severely compromised patients to long term institutions. This study was undertaken to evaluate whether changing concepts in community geriatric care and criteria for admission to long term hospitals were reflected in the oral status and the treatment level of geriatric hospital patients. The study confirms that the inmates were older and more medically compromised and that the change was discernible during such a short period of time as two years. Edentulousness had decreased from 30 percent to 24 percent. The mean number of remaining teeth was 15.2 in 1988 and 13.0 in 1990. The content of treatment had changed between 1988 and 1990. The dentist had adjusted the treatment level to the patient's condition and to the unexpected shortage of dental personnel. It can be concluded that the maintenance of life-long good oral health demands life-long regular dental care, with an increasing content of professional preventive care in long term care at home or in hospital. PMID- 8362364 TI - Successful financial arrangements: a team approach. PMID- 8362363 TI - An evaluation of image quality for the assessment of the marginal bone level in panoramic radiography. A comparison of radiographs from different dental clinics. AB - The diagnostic image quality of panoramic radiographs originating from different clinics was examined. Two samples of 98 and 100 radiographs, respectively, were from a department of oral radiology. The radiographs of one of these samples were checked using immediate subjective analysis of the image quality before inclusion in the study whereas the radiographs of the other sample were randomly selected. A third sample consisted of radiographs from 20 randomly selected dental clinics. The subjective overall image quality of the whole panoramic radiograph was classified as adequate, marginal or inadequate. The three observers also assessed the reason for inferior image quality. The overall image quality of the radiographs was better for the checked sample from the department of oral radiology compared to the sample form the 20 dental clinics. The main reason for unacceptable image quality of the radiographs was too low density and/or contrast irrespective of sample. Other faults were incorrect positioning of the patient but in the sample from the 20 clinics improper film handling was also frequent. We conclude that image quality in panoramic radiography can be improved. Improvement of the image quality is a prerequisite if panoramic radiography in the future is to replace the full-mouth examination. PMID- 8362365 TI - High mutation rate loci in a subdivided population. AB - Analytic and simulation studies were carried out in order to predict the average geographic area occupied by alleles in a continuously distributed population. The properties of three statistics were investigated: the sum of the squared distances between members of allelic classes, the sum of the root mean squared distances, and the sum of the squares of the numbers of alleles. The expectations of these quantities can be obtained analytically from both stepping-stone and branching diffusion models. The predictions of these two models are similar for wide ranges of parameter values and are consistent with the simulation results from a stepping-stone model. These results suggest that measures of the geographic distribution of alleles can be useful for estimating average dispersal distances at loci, such as minisatellite and microsatellite loci, at which mutation rates are high enough that they can be estimated with confidence. PMID- 8362366 TI - Two-state spatial dynamics in the absence of age. AB - This paper investigates the simplest multistate population model, a one-age group, two-living-state model with constant rates of birth, death, and interstate movement. A general solution for the model is presented, and special attention is given to the process of convergence to stability and its relationship to spatial population momentum. The constant ultimate level of the speed of convergence, or the intrinsic force of convergence, is found to be twice the difference between the two eigenvalues of the model's transition matrix. Spatial population momentum is shown to be directly proportional to the initial growth rate of the population under the stationary rates and inversely proportional to the intrinsic force of convergence. A population increases in size during the transition to zero growth only when the faster growing state is a larger fraction of the initial population than of the stationary population. Hypothetical calculations with an urban/rural population model illustrate the importance of the speed of convergence, and show the great growth potential inherent in spatial momentum. PMID- 8362367 TI - The establishment of underdominant chromosomal rearrangements in multi-deme systems with local extinction and colonization. AB - The fate of an underdominant chromosomal mutant was investigated in multideme models with high rates of local extinction and colonization. Four models with different patterns of colonization (number of colonists and place of origin of colonists) were studied by performing a large number of computer simulations with the Monte Carlo method for several sets of values of the following parameters: coefficient of selection against the heterozygote, extinction rate of each deme, deme size, and number of demes. The probability of the newly arisen rearrangement being established in the multi-deme system depends strongly on the pattern of colonization, other things being equal. In the three models in which there is absent or scarce mixing of gene pools of different demes when a new deme is founded, the fixation probability of the new chromosomal rearrangement is rather close to that calculated by R. Lande (1979, Evolution 33, 234-251; 1985, Heredity 54, 323-332), which is equal to the corresponding probability in a single deme divided by the number of demes. In the model with extensive mixing of gene pools of demes, the corresponding probability is lower (considerably in some cases). Furthermore, in the models where the fixation probability is higher, the analysis of the time of the process leads to the conclusion that in systems consisting of a large number of demes, overlapping of several different processes of fixation of chromosomal rearrangements occurs. PMID- 8362368 TI - PPACK attenuates plasmin-induced changes in endothelial integrity. AB - In order to determine whether plasmin affects endothelial cell integrity directly, confluent bovine aortic endothelial cells were treated with plasminogen and a plasminogen activator. The permeability of the monolayer to [125I]-albumin was shown to be increased significantly (P < 0.01) with a concomitant decrease in viability. Plasmin activity correlated significantly with endothelial cell permeability (p < 0.004; r = 0.82). Coincubation with D-phenylalanyl-L-prolyl-L arginyl chloromethylketone, a tripeptide inhibitor of plasmin, reduced the increase in endothelial permeability induced by plasmin by 59% (p = 0.033). Monolayers studied in parallel were stained with rhodamine-phalloidin to visualize F-actin. There were significant morphologic changes in the endothelial monolayers exposed to plasmin compared to control monolayers, and these changes could be attenuated by coincubation with D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone. These studies show that: 1) plasmin induces significant increases in endothelial cell permeability with accompanying morphologic changes; and 2) these deleterious functional and morphologic effects can be attenuated by coincubation with the plasmin inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone. PMID- 8362369 TI - Comparison of the sequence of fibrinopeptide A cleavage from fibrinogen fragment E by thrombin, atroxin, or batroxobin. AB - In order to investigate the sequence of fibrinopeptide release from the amino terminal end of a dimeric fibrinogen-derived substrate by thrombin or batroxobins, we studied their effects on plasmic fragment E1, a core fragment from the central domain of fibrinogen containing both A alpha chain fibrinopeptide A (FPA) sequences. Isoelectric focussing (IEF) was employed as a means of resolving des A-fragment E1, from which one FPA had been cleaved, from des AA-fragment E1 resulting from the loss of both FPA's. Using densitometric gel scanning for quantification of the levels of intact fragment E1, des A-fragment E1, and des AA-fragment E1, in mixtures incubated with enzyme for various periods of time, we found similar catalytic rate constants (k1, k2) for release of the first fibrinopeptide A, (FPA1) or the second, (FPA2) from fragment E1, with either thrombin or batroxobin (k2:k1 ratios of 1.10 +/- 0.42, 1.34 +/- 0.26 respectively). Atroxin released FPA2 more slowly than FPA1 with a k2:k1 ratio of 0.34 +/- 0.1. Th finding that the cleavage of FPA2 by Atroxin is three-fold slower than thrombin and almost four-fold slower than batroxobin, suggest that batroxobin and thrombin cleavage of FPA2 may be cooperative in nature. However, the cooperativity in the cleavage sequence is insufficient to markedly suppress the evolution of intermediate des A fragment E species during early and intermediate phases of FPA cleavage from fragment E. PMID- 8362370 TI - Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery. AB - Hip joint replacement surgery, using acrylic cement for prosthesis fixation, is associated with intraoperative cardiorespiratory dysfunction, and a high frequency of postoperative proximal deep vein thrombosis (DVT). Levels of prothrombin fragments 1+2 (F1+2), tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), D-dimer and interleukin 6 (IL 6) were measured in arterial (AB) and mixed venous blood (MVB) in five patients during and after total hip replacement operation with acrylic cement prosthesis fixation. Sequential peaks of F1+2, t-PA, PAI-1 and IL-6 appeared, starting with activation of coagulation during preparation of bone, closely followed by activation of fibrinolysis. Later, this was counteracted by an antifibrinolytic response and increase of IL-6. After a fibrinolytic shutdown on the third postoperative day as evidenced by a drop in t-PA and D-dimer concentrations, a second wave of coagulation was seen at the end of the first week. The present model, with frequent sampling of blood entering and leaving the lungs, confirms our earlier findings of the lung as a key organ in promoting coagulation following traumatic activation. PMID- 8362371 TI - Regulation of endothelial cell protein C activation and fibrinolysis by procoagulant albumin. AB - Endothelial cell regulation of protein C activation and fibrinolysis are important components of the hemostatic response to vascular injury or perturbation. Procoagulant albumin (P-A1), a constituent of normal human plasma has been purified and identified as an inducer of endothelial cell tissue factor activity. The purpose of the studies reported herein was to investigate the effects of P-A1 on human endothelial cell protein C activation and fibrinolysis. P-A1 suppressed protein C activation, enhanced release of plasminogen activator inhibitor-1, but had no effect on tissue-plasminogen activator release. Plasminogen activator inhibitor-1 released by P-A1 was functional as evidenced by the capacity to form a covalent complex with 125I-urokinase. Inactive albumin (isolated during the same purification procedure as P-A1, but without tissue factor-inducing activity) did not suppress protein C activation or increase plasminogen activator inhibitor-1 release. These results indicate that P-A1, a component of human plasma, can modulate multiple vascular hemostatic properties, and support the hypothesis that P-A1 is involved in normal or pathologic hemostasis. PMID- 8362372 TI - Purification and characterisation of a snake venom phospholipase A2: a potent inhibitor of platelet aggregation. AB - An inhibitor of human platelet aggregation was identified from the venom of an Australian Copperhead snake, Austrelaps superba, as a novel phospholipase A2. The inhibitor was purified to homogeneity by chromatography on Q-Sepharose, S Sepharose and C8 reverse phase HPLC. The purified phospholipase A2 has a molecular weight of 15 kDa as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). N-terminal sequence analysis of the platelet inhibitor revealed 70-80% sequence identity to other previously described secretory phospholipase A2. Phospholipase activity of the purified protein was confirmed by the ability of the enzyme to hydrolyse lecithin. Pretreatment of the purified protein with the specific phospholipase A2 inhibitor p-bromophenacyl bromide, resulted in abrogation of both its enzyme and platelet inhibitory activity. The phospholipase A2 inhibited platelet aggregation and serotonin release, induced by a variety of platelet agonists, in a time and dose dependent manner. PMID- 8362373 TI - Protein C and protein S in patients with peripheral arterial occlusive disease. PMID- 8362374 TI - Inhibition of heparin/antithrombin III cofactor activity by anticardiolipin antibodies: a mechanism for thrombosis. AB - Anticardiolipin antibodies (aCL) are autoantibodies which react with negatively charged phospholipids and are associated with thrombotic disease and recurrent fetal loss. We have found that 11% of aCL are cross-reactive with the glycosaminoglycans heparin and heparan sulphate. One of these antibodies was studied in detail and was found to inhibit the heparin dependent activation of antithrombin III by up to 80%. The inhibition of heparin dependent antithrombin III activation represents a new mechanism by which anticardiolipin antibodies may induce thrombosis or fetal loss in some patients with these antibodies. PMID- 8362375 TI - Reactive oxygen intermediates and ischemia-reperfusion injury release tissue plasminogen activator from isolated rat hearts. AB - Tissue plasminogen activator (t-PA) is a marker of endothelial cell injury or activation. The release of t-PA from isolated rat hearts (Langendorff model) subjected to ischemia-reperfusion or reactive oxygen intermediates (ROI) generated by H2O2 was investigated. H2O2 (200 microM) increased t-PA activity in the coronary effluent to 305 +/- 84% of initial value (mean +/- SEM, p < 0.04 vs controls) at the end of a 10 min intervention. The hydroxyl radical scavenger thiourea (10 mM) only partially inhibited the increase (175 +/- 27%, p < 0.01 compared to controls). 20 min normothermic ischemia increased t-PA activity to 416 +/- 108% (p < 0.005 compared to controls) at the start of reperfusion. In conclusion, cardiac injury by ischemia-reperfusion or ROI increases release of t PA. PMID- 8362376 TI - Fibrin--recombinant human factor XIII a-subunit association. AB - The association of factor XIII a-subunits with fibrin was characterized using recombinant human placental factor XIII (rFXIII) and native fully hydrated fibrin clots formed from purified fibrinogen and thrombin. Binding was assessed using small columns containing fibrin and perfusing them with radioiodinated rFXIII. Results show that thrombin activation of rFXIII led to fibrin binding. The association was partially reversible since much of the bound enzyme could be removed by percolating clots with more buffer. Binding was blocked by antibody directed against the COOH-terminal part of fibrinogen A alpha-chain (A alpha 389 402) and also by the COOH-terminal A alpha-chain peptide fragment A alpha 241-476 (Hi2-DSK). PMID- 8362377 TI - Suppressive effect of human blood coagulation factor XIII on the vascular permeability induced by anti-guinea pig endothelial cell antiserum in guinea pigs. AB - We investigated the effect of blood coagulation factor XIII (FXIII) on enhanced permeability induced by anti-endothelial cell antiserum, that was produced by the immunization of guinea pig endothelial cells with adjuvant into rabbits repeatedly. We have found that this antiserum reacts to human and guinea pig endothelial cells but not guinea pig fibroblast cells. The permeability was enhanced by intradermal injection of 400-fold dilution of this antiserum into dorsal skin of guinea pigs. The mixture of equal volume of antiserum and FXIII was intradermally injected into dorsal skin of guinea pig after Evans blue injection, and 15 minutes later the quantity of Evans blue at the each injection site was determined. We recognized the suppressive effect of FXIII on the dye leakage. We also studied the suppressive effect on swelling induced by the antiserum. After the subcutaneous injection of the mixture of antiserum and FXIII into the back of guinea pigs, we measured the thickness of skins at the injection site after day 1, 2 and 3. As a result, FXIII significantly suppressed the swelling. We found that FXIII suppresses the acute and subacute permeability enhancement. These results suggest that FXIII plays an important role on an inflammatory site and that it may exert as an anti-inflammatory protein. PMID- 8362378 TI - The effect of short-term exercise on plasma procoagulant activity in patients with type II (non-insulin-dependent) diabetes and healthy volunteers. AB - The effect of exercise on plasma coagulant activity was studied in 16 subjects with newly-diagnosed type II diabetes without vascular complications and 9 healthy volunteers. Generation of thrombin was determined by a computer-assisted chromogenic method and results expressed as time to generate 50% maximal thrombin activity (T50/s). In addition, APTT, factor VIII and thrombin-antithrombin III (TAT) complex levels were measured. Pre-exercise FVIII:C [mean (+/- SD)] was increased in diabetic compared to control subjects [1.5 (0.4); 0.9 (0.2) IU ml-1; (p < 0.001) respectively]. No significant differences in APTT, TAT or T50 were detected between the groups. Exercise induced a rise in FVIII complex, reduction of APTT [33 (2) s to 31 (2) s; (p = 0.004)] and T50 [58 (6) s to 53 (6) s; (p = 0.01)] in controls and an increase in FVIII complex but no significant changes in APTT or T50 in diabetic patients, with no change in TAT in either group. A greater increase in FVIII:C than vWF levels occurred in controls [0.2 (0.1); 0.1 (0.1) IU ml-1; (p = 0.005)] and patients [0.3 (0.4); 0.2 (0.1) IU ml-1; (p = 0.032)]. In patients, FVIII:C correlated inversely with APTT (r = -0.522, p = 0.038) and T50 (r = -0.592, p = 0.016). The results show that FVIII:C levels are increased at diagnosis in patients with type II diabetes without vascular disease but there is no enhancement of plasma procoagulant activity. In healthy individuals, exercise induced activation of coagulation which was not seen in patients, suggesting that it does not precipitate a state of accelerated thrombogenesis in subjects with uncomplicated type II diabetes. PMID- 8362379 TI - Role of the platelet integrin glycoprotein IIb-IIIa in intracellular signalling. PMID- 8362380 TI - Anticoagulant and antithrombotic action of the factor Xa inhibitor antistasin (ATS). PMID- 8362381 TI - [Disability insurance on the decline]. PMID- 8362382 TI - [Seizures and traffic risks]. PMID- 8362383 TI - [Physicians and drivers' licences]. PMID- 8362384 TI - [Serotonin antagonists against nausea and vomiting induced by oncologic therapy]. PMID- 8362386 TI - [Role of phospholipids in hemostasis]. AB - This article reviews the significance of phospholipids in the haemostatic process. The plasma membranes of activated human blood platelets provide a catalytic phospholipid surface on which the "tenase" complex (factor IXa-factor VIIIa) and the "prothrombinase" complex (factor Xa-factor Va) can be assembled. The formation of a procoagulant platelet surface involves the exposure of anionic phospholipids e.g. phosphatidylserine, and is associated with shedding of microvesicles from the membranes of activated platelets. Moreover, tissue-factor, which plays a key role in blood coagulation by initiating the extrinsic coagulation pathway, requires the presence of phospholipids for optimal biological activity. The phospholipid dependency of the coagulation system explains the prolongation of phospholipid dependent clotting tests in patients with phospholipid directed antibodies such as lupus anticoagulants. PMID- 8362385 TI - [On what indication should serotonin antagonists be used? A retrospective study of the use of ondansetron at an oncologic unit]. AB - 561 chemotherapy-cycles administered to 191 patients during the period 1990-92 at the University Hospital, Tromso, were retrospectively analysed for combination with ondansetron. 65% of the cycles were combined with ondansetron. The frequency increased from 1991 (50%) to 1992 (69%). Among moderate emetogenic regimens (MIME, MMM, High-dose MTX, EBVP, ELF) the frequency had changed from 44% to 91%. The increased ondansetron-treatment in moderate emetogenic regimens raised the total cost of treatment. Better cost-effectiveness can possibly be achieved by "low dose-ondansetron" (4 mg x 2) and more frequent supplementary use of diazepam, corticosteroids or haloperidol. Use of ondansetron regimens extending beyond 24 hours is not cost-effective. Peroral treatment is less expensive and usually adequate to control acute emesis. PMID- 8362387 TI - [Therapeutic drug monitoring with the help of serum concentration measurements. How are the analytic results distributed in a population?]. AB - Therapeutic drug monitoring includes measurement of serum concentrations of drugs when this is possible and appropriate. A therapeutic range is defined for populations where the serum levels represent an optimal relationship between clinical effects and side effects for most of the individuals in the population. Compared with the rest of the population, some individuals are atypical, both with respect to response to and elimination of drugs. Therapeutic drug monitoring makes individualization of dosages in these individuals easier, but often requires extra effort. Compilation of serum level measurements for different drugs for a period of six months showed that the tailoring of digitoxin, carbamazepine, lithium and phenobarbital is as close to optimal as can be expected for a population. For amitriptyline, digoxin and theophylline, a considerable increase in clinical effect within a population of users could probably be achieved by bringing more individual serum levels from the subtherapeutic into the therapeutic range. Nor does the therapeutic potential of phenytoin, nortriptyline and valproate seem to be fully utilized. PMID- 8362388 TI - [Infantile autism among children in the county of Nordland. Prevalence and etiology]. AB - Few epidemiological studies of infantile autism have been conducted in Norway. A prevalence of four per 10,000 children was found in Nord-Trondelag. Studies from Sweden, England and Japan show prevalence figures of 2-13 per 10,000. Causal factors of autism are complicated, but many studies in recent years indicate that both genetic and neurological factors are important. The aim of this study was to establish the prevalence of infantile autism in Nordland county and look for causal factors and disabilities among the children. Together with the Autism-Team we found 28 persons, born between 1975 and 1991, who lived in the county in 1992. This gives a prevalence of 5.5 per 10,000. 21 were boys, seven girls, 26 were mentally retarded, 13 had no verbal speech. Nine had epilepsy. 13 children were diagnosed before the age of four. Different diseases and impairments associated with autism were discovered in 19 children. In the case of eight children we found associated disease. When a diagnosis of infantile autism is made, the child should undergo a thorough medical and neurological examination. This should include CT brain scan, EEG, chromosome analysis, and screening for metabolic diseases and intrauterine virus infections. Sometimes examinations of liquor and auditory brain-stem responses are indicated. PMID- 8362389 TI - [Eosinophilic gastroenteritis]. AB - We describe the case of a 33 year-old woman who was hospitalized for ascites, abdominal pain and food allergy. Blood samples and histologic examination of a jejunal specimen removed by laparotomy revealed that the patient suffered from eosinophilic gastroenteritis. This disease is classified among the hypereosinophilic syndromes, and food allergy may be of etiologic importance. Clinically eosinophilic gastroenteritis may present with ascites, malabsorption or gut obstruction. The eosinophilic blood cell count is usually elevated and the erythrocyte sedimentation rate is usually normal or slightly increased. Polyarteritis nodosa, Crohn's disease and nematodal infections of the gut must be excluded. Most patients respond well to corticosteroid therapy and the long-term prognosis is good, even though the disease is chronic in nature. PMID- 8362390 TI - [Pulmonary embolism as a late complication of heart contusion]. AB - A 57 year-old woman was hospitalized because of a sternal fracture inflicted during a car accident. During the following two weeks she became breathless and was readmitted after having syncope, induced by exertion. A perfusion scan of the lungs showed pulmonary emboli in both the lower lobes. After anti-coagulation treatment her symptoms faded, but the ultrasonographic signs of pulmonary hypertension persisted for nearly four months. The probable mechanism behind the pulmonary embolism was transmural contusion of the right ventricle, leading to a mural thrombus which eventually became detached. The authors review the literature and discuss problems connected to the diagnostic criteria for cardiac contusion, as well as delayed complications, of which pulmonary embolism is a potentially lethal condition. PMID- 8362391 TI - [Cystitis cystica--a premalignant condition?]. AB - Although cystitis cystica is considered to be a premalignant disease of the urinary bladder, remarkably few reports document the progression from cystitis cystica and glandularis to carcinoma of the bladder. We describe three patients where cystitis cystica was demonstrated 12, three and one month before diagnosis of cancer. We believe cystitis cystica reflects mobilization of the humoral immune defence mechanism in response to various agents, among these a subclinical malignant tumour. PMID- 8362392 TI - [Brodie's abscess]. AB - Brodie's abscess is a localized subacute or chronic osteomyelitis independent of any known previous acute infection. The entity is often mistaken for a bone tumour. The diagnosis requires biopsy. The treatment is curettage, drainage and antibiotics for a minimum of six weeks. We describe the characteristics of Brodie's abscess and describe a patient with an illustrating history, but with an unusual localization of the abscess (osilium). PMID- 8362393 TI - [Adenocarcinoid (mucinous carcinoid) of the vermiform appendix]. AB - Adenocarcinoid (mucinous carcinoid or goblet cell carcinoid) is an unusual tumour of the appendix with histologic and prognostic features between those of carcinoid and adenocarcinoma. Most patients with adenocarcinoid tumours of the appendix present with symptoms consistent with those of acute appendicitis. We describe a 31 year-old male who presented with such symptoms. Ultrasonography demonstrated an acutely inflamed appendix with a hypoechoic area in the midportion of the appendix, suspicious of a tumour. This rare type of tumour is briefly presented. PMID- 8362394 TI - [Poisonings and gas accidents]. AB - Recent trends in the treatment of acute poisoning, including exposure to gas, are briefly discussed. According to the new WHO/IPCS guidelines, a more restrictive use of gastric lavage and induction of emesis is recommended. Toxicokinetic evaluation of the efficacy of elimination procedures has lead to very few remaining indications for haemoperfusion, and forced acidic diuresis is no longer recommended. PMID- 8362395 TI - [Coma from cerebral and metabolic causes]. AB - The medical causes of coma fall into two main categories: intercranial diseases, and metabolic disturbances. The clinical examination should define 1) vital functions, 2) depth of coma, 3) whether cerebral signs are diffuse or local, 4) any signs of organ disease. The blood sugar level must be determined. Hypoglycemia may be the cause even if the signs point to another cause. Head injury and intoxication/poisoning must always be considered, even if a medical cause is suspected. Prolonged coma calls for repeated clinical and laboratory examination. Combinations of causes, e.g. organ disease plus intoxication should be considered. PMID- 8362396 TI - [Phospholipid antibodies (lupus anticoagulant and cardiolipin antibodies). Detection and clinical significance]. AB - Phospholipid antibodies may be detected by their ability to prolong phospholipid dependent coagulation tests, and are then called lupus anticoagulants. When ELISA tests with cardiolipin as coating antigen are used, the term anticardiolipin antibodies is employed. The association with thrombosis is best documented in patients with systemic lupus erythematosus. However, the "antiphospholipid syndrome", i.e. repeated thrombotic episodes and/or foetal loss in combination with a high positive anticardiolipin antibody test and/or an unequivocally positive lupus anticoagulant test, may be seen in individuals without any known underlying disease. The article describes techniques for the detection of antiphospholipid antibodies and adequate processing and handling of plasma samples. PMID- 8362397 TI - [Driver's licence and seizures]. AB - The authors consider various types of seizures and their medico-legal consequences in connection with motor vehicle driving. Epilepsy, syncope, transitory ischemic attacks, migraine, electrolyte disturbances, hypoglycaemia, hypersomnia, and alcohol-induced fits are discussed in brief. The authors also discuss risk of recurrence, the seizure-free interval before driving can be resumed, and possible mitigating factors. PMID- 8362398 TI - [Driver's licenses and medicine. A review of legal requirements and practice]. AB - There are health requirements for acquiring and renewing a driver's license. Physicians are legally obliged to inform the local health authorities when a patient no longer meets these health requirements. This paper describes the current Norwegian legislation, formalities of administration, and practice of traffic medicine. Visual acuity, field of vision, seizures, heart disease, diabetes mellitus, abuse of alcohol and drugs, psychiatric disorders, aging and dysfunction of the locomotor system are discussed in brief. PMID- 8362399 TI - [Detection of antibodies in erythema infectiosum--now also possible in Norway]. PMID- 8362400 TI - [Mononucleosis and neurologic manifestations]. PMID- 8362401 TI - [Treatment of endocrine diseases in adolescents and adults]. PMID- 8362402 TI - [More adverse effects of EDP]. PMID- 8362403 TI - [Refugees and immigrants]. PMID- 8362404 TI - [Jumper's knee or take-off knee?]. PMID- 8362405 TI - [Joint European monitoring of differences in health care. A description of practices established by the European Community for reporting accidents and near accidents in relation to the use of medical technology]. PMID- 8362406 TI - [Personnel crisis of Norwegian laboratory medicine]. PMID- 8362407 TI - [Useful drug information on CD-ROM]. PMID- 8362408 TI - Sequence-specific oligonucleotide typing in Shona patients with rheumatoid arthritis and healthy controls from Zimbabwe. AB - Seventy-two patients with rheumatoid arthritis (RA) and 82 controls have been typed with the XI Histocompatibility Workshop DRB1 and DQB1 sequence-specific oligonucleotide probes. The increase of DRB1*04 corresponds to an increase of the serologically defined DR4, previously found in a small group of Zimbabwean RA patients and we now show that this increase is due to the subtype DRB1*0405 in association with DQB1*0302. In addition there is a clearcut increase of DRB1*1001 equivalent to the serologically defined DR10. There was no increase amongst RA patients of DRB1*0102 which was the predominant DR1 sub-type amongst controls. In the course of our investigation, we observed a DRB1*04 variant which corresponds to DRB1*0412, newly defined in the XIth Histocompatibility Workshop. PMID- 8362409 TI - On the HLA-DQ(alpha 1*0501, beta 1*0201)-associated susceptibility in celiac disease: a possible gene dosage effect of DQB1*0201. AB - The HLA-associated susceptibility to develop celiac disease (CD) seems mainly to be conferred by a particular HLA-DQ heterodimer encoded by the DQA1*0501 and DQB1*0201 genes either in cis or in trans position. To study the possible influence of DRB1 or other DQA1 and DQB1 alleles on the CD susceptibility conferred by these DQ genes, we performed genomic HLA typing of 94 CD patients, selected those who carried at least one copy of the DRB1*0301-DQA1*0501-DQB1*0201 haplotype (N = 89) and compared them to 47 random, healthy Norwegians matched with the patients to carry at least one copy of the above haplotype. We found an excess of DQB1*0201 homozygosity in the patients. This was due to an increased frequency of the DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*0701-DQA1*0201-DQB1*0201 haplotypes present on the other chromosome. We propose that, in individuals carrying the DQA1*0501 and DQB1*0201 alleles, the presence of a second copy of the DQB1*0201 allele increases susceptibility to CD. PMID- 8362411 TI - Primary structure shows HLA-B59 to be a hybrid of HLA-B55 and HLA-B51, and not a subtype of HLA-B8. PMID- 8362410 TI - A human monoclonal antibody that detects HLA-A1, A23 and A24 antigens. AB - We report the production and characterization of a human monoclonal IgM (mu, kappa) antibody recognizing the HLA A1, A23 and A24 antigens. B lymphocytes obtained from a multiparous Japanese woman were transformed in vitro by Epstein Barr virus, screened with an immune adherence assay, and fused with a murine myeloma cell line, P3-X63-Ag8.653. After subcloning by limiting dilution three times, a stable antibody-secreting hybridoma cell line, 4-35-7, was identified. The culture supernant had a titer of 1:32-64 against each of A1-, A23- and A24 positive lymphocyte panels, and showed complete correlation (r = 1.00) with the A1, A23 and A24 antigens on a lymphocyte panel of 287 unrelated, class I HLA typed donors by the NIH cytotoxicity assay. Monoclonality of the antibody was ensured by Southern blot analysis of the human immunoglobulin heavy chain gene of 4-35-7. In view of the published data on HLA class I nucleotide sequences, the antibody may recognize an antigeneic determinant including two amino acid residues, Asp-166 and Gly-167, in the alpha 2 helix of the class I molecule that are specific for A1, A23 and A24 so far analyzed. PMID- 8362412 TI - A monospecific HLA-B27 fluorescein isothiocyanate-conjugated monoclonal antibody for rapid, simple and accurate HLA-B27 typing. PMID- 8362413 TI - A new DR11 allele in Singaporean Chinese. PMID- 8362414 TI - A new HLA Cw6 split -Cw6.2- detected in three ethnic groups that is inherited in families. PMID- 8362415 TI - Molecular analysis of a novel HLA-A33 subtype associated with HLA-B44. PMID- 8362416 TI - Structural and biosynthetic features of the Mo5 human myeloid differentiation antigen. PMID- 8362417 TI - Simplified preparation from anti-coagulated blood for HLA-DR genomic typing. PMID- 8362418 TI - Carotid endarterectomy and the measurement of stenosis. PMID- 8362419 TI - Predicting complications of carotid endarterectomy. AB - BACKGROUND AND PURPOSE: Carotid endarterectomy has been shown to be beneficial in patients with high-grade carotid stenosis and ipsilateral transient ischemic attack or stroke. This benefit will be realized only if the operation is performed safely. We sought to determine the extent to which clinically significant adverse events occurring after carotid endarterectomy can be predicted from clinical data available before surgery. METHODS: Eleven hundred sixty patients were randomly selected from all patients who underwent carotid endarterectomy and were discharged during the calendar years 1988, 1989, and 1990 in 12 academic medical centers in 10 states. Clinical data abstracted from hospital charts were analyzed retrospectively. A model was developed and validated to predict the occurrence of stroke, myocardial infarction, or death during the postoperative period of hospitalization. RESULTS: Eight patients (6.9%) suffered at least one adverse event. Rates for individual complications were as follows: death, 1.4%; nonfatal stroke, 3.4%; nonfatal myocardial infarction, 2.1%; and nonfatal stroke or death, 4.8%. Significant predictors of adverse events were age 75 years or older, symptom status (ipsilateral symptoms versus asymptomatic or nonipsilateral symptoms), severe hypertension (preoperative diastolic blood pressure of greater than 110 mm Hg), carotid endarterectomy performed in preparation for coronary artery bypass surgery, history of angina, evidence of internal carotid artery thrombus, and internal carotid artery stenosis near the carotid siphon. The presence of two or more of these risk factors was associated with a nearly twofold increase in risk of an adverse event (relative risk, 1.7; 95% confidence interval, 1.0 to 3.0). CONCLUSIONS: Clinical data can be used to stratify patients undergoing carotid endarterectomy according to risk of postoperative in-hospital stroke, myocardial infarction, or death. PMID- 8362420 TI - Measuring carotid stenosis. Time for a reappraisal. AB - BACKGROUND AND PURPOSE: Data from recent multicenter carotid endarterectomy trials have questioned the validity and reliability of Doppler ultrasound in the assessment of carotid stenosis. METHODS: We prospectively analyzed 45 patients undergoing carotid angiography to compare the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) methods of measuring carotid stenosis with those of direct visualization ("eyeballing") and duplex ultrasound. Linear NASCET and ECST measurements were also converted into area using the pi r2 function and termed "squared NASCET" (N2) and "squared ECST" (E2). In 15 of 45 patients undergoing carotid endarterectomy, the carotid plaque was removed intact, sectioned, and photographed for computer measurement of cross-sectional area. Comparison of this "gold standard" was then made to each method of measurement. RESULTS: Comparison between duplex and the various angiographic measurement techniques revealed significant differences between NASCET and duplex (P < .0001), ECST and duplex (P < .01), and E2 and duplex (P < .01) but not between N2, eyeballing, and carotid duplex methods. Even the NASCET and ECST methods themselves differed significantly (P < .006). When comparison was made with computerized planimetric measurements of the carotid plaque, there were significant differences for both NASCET (P < .0007) and ECST (P < .007). Correlation was demonstrated only between planimetry and N2, E2, and duplex. CONCLUSIONS: NASCET and ECST angiographic methods of measurement consistently underestimate the "true" anatomic stenosis. As such, they represent only "indexes" of carotid stenosis severity. Duplex provides a more accurate measurement of carotid stenosis. PMID- 8362421 TI - Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators. AB - BACKGROUND AND PURPOSE: B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article provides a description of the distribution of carotid atherosclerosis in the general population. METHODS: Intimal-medial arterial wall thickness was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The distribution was described by race-sex strata, in which 759 to 4952 individuals were imaged depending on strata and location in the carotid system. RESULTS: Median wall thickness ranged between 0.5 and 1 mm at all ages; fewer than 5% of ARIC participants had values exceeding 2 mm. Individuals tended to have a larger wall thickness in the carotid bifurcation than in the common carotid artery. Internal carotid artery values were more variable, with higher proportions of both large and small wall thicknesses than in the common carotid. The proportion of individuals with a large wall thickness was greatest at the bifurcation and smallest at the common carotid artery. Men had uniformly larger wall thickness than women. Cross-sectional analysis suggests that age-related increases in wall thickness average approximately 0.015 mm/y in women and 0.018 mm/y in men in the carotid bifurcation, 0.010 mm/y for women and 0.014 mm/y for men in the internal carotid artery, and 0.010 mm/y in both sexes in the common carotid artery. CONCLUSIONS: Estimates provided for wall thickness percentiles can serve as "nomograms" by age, race, and sex. PMID- 8362422 TI - Transcranial color duplex sonography in childhood and adolescence. Age dependence of flow velocities and waveform parameters. AB - BACKGROUND AND PURPOSE: Transcranial color duplex sonographic examinations in children and adolescents without cerebrovascular disease were evaluated retrospectively. Flow velocities and waveform parameters were determined and their side-to-side differences and age dependence analyzed and, finally, compared with analogous data of a previously described group of healthy adults. METHODS: With a 2.0-MHz sector transducer of a computed sonographic system, the anterior, middle, and posterior cerebral arteries were examined in 64 children and adolescents between 1.5 and 17.5 years of age. Angle-corrected systolic peak, end diastolic maximum, time-averaged, and time-averaged maximum velocities, and the resistance, pulsatility, and spectral broadening indexes were determined in all vessels. RESULTS: Mean +/- SD values for time-averaged maximum velocity (and time averaged velocity) were 92.2 +/- 13.0, 79.9 +/- 17.7, and 63.9 +/- 13.6 (55.3 +/- 11.7, 40.4 +/- 10.4, and 34.2 +/- 9.2) cm/s, respectively, in the middle, anterior, and posterior cerebral arteries in children under 10 years of age; values were 83.2 +/- 11.9, 69.4 +/- 13.8, and 55.6 +/- 10.1 (50.8 +/- 9.0, 39.9 +/- 10.5, and 33.1 +/- 6.3) cm/s, respectively, in children 10 years of age and older. Time-averaged maximum velocity decreased significantly with age in all vessels (P < .001). Although time-averaged velocity did not change significantly during childhood and adolescence, a clear decline occurred from adolescence to adulthood (P < .0001 in the middle and posterior cerebral arteries; P < .01 in the anterior cerebral artery). The spectral broadening index decreased significantly from childhood to adolescence in the anterior and posterior cerebral arteries (P < .0001). The resistance and pulsatility indexes remained stable throughout childhood. CONCLUSIONS: Transcranial color duplex sonography allows angle-corrected measurements of "true" flow velocities in basal cerebral arteries. Additional determination of time-averaged velocity permits more detailed evaluation of flow characteristics for all age groups. The transcranial color duplex technique may provide deeper insights on normal cerebral perfusion and its disorders. PMID- 8362423 TI - Magnetic resonance angiography in vertebrobasilar ischemia. AB - BACKGROUND AND PURPOSE: Magnetic resonance angiography is a new, noninvasive technique whose diagnostic value in vertebrobasilar artery disease has not yet been determined. METHODS: Forty-one patients with acute cerebellar and/or brain stem ischemia were examined by routine magnetic resonance imaging, extracranial and transcranial Doppler ultrasound, and selective intra-arterial arteriography. Results were correlated with magnetic resonance angiography. Magnetic resonance angiography was accomplished using a three-dimensional time-of-flight gradient echo technique. RESULTS: Magnetic resonance angiography correctly identified all occlusions, stenoses, and an aneurysm within the distal vertebrobasilar system as revealed by conventional intra-arterial arteriography but missed the diagnosis of vertebral artery dissection in one case. This results in a sensitivity of magnetic resonance angiography of 97% and a specificity of 98.9%. However, the degree of stenoses was difficult to evaluate by magnetic resonance angiography. At least for severe obstructive lesions, this drawback can be eliminated by application of presaturation pulses, which allow the analysis of flow direction and collateral blood flow. Doppler ultrasound studies add useful hemodynamic information for less severe degrees of stenoses. CONCLUSIONS: The combined use of magnetic resonance angiography and Doppler ultrasound findings may replace the invasive intra-arterial arteriography examination in many patients with suspected macroangiopathy of the vertebrobasilar arteries. PMID- 8362424 TI - Longitudinal changes in proton magnetic resonance spectroscopy in cerebral infarction. AB - BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy has revealed changes in lactate and N-acetyl-aspartate in acute cerebral infarction. However, the details of these drastic changes and subsequent chronic changes have not been clarified. The purpose of this study was to disclose longitudinal changes in spectra seen in proton magnetic resonance spectroscopy. METHODS: Six patients with completed cerebral infarction were examined longitudinally with localized proton magnetic resonance spectroscopy. RESULTS: (1) In the acute stage (within 2 days after onset), two drastic changes were observed: N-acetyl-aspartate decreased rapidly and severely within 2 days after onset, and lactate increased immediately and reached a high level in the acute stage after onset. (2) In the chronic stage (more than 1 month after onset), two features were observed: lactate, which had increased in the acute stage, remained high for more than 1 month, and other signals such as those of N-acetyl-aspartate, choline, and phosphocreatine/creatine decreased dramatically. CONCLUSIONS: These results suggest that N-acetyl-aspartate and lactate as revealed by proton magnetic resonance spectroscopy can be useful indicators of the ischemic damage to the brain in clinical cases of cerebral infarction. PMID- 8362425 TI - Value of single-photon emission-computed tomography in acute stroke therapeutic trials. AB - BACKGROUND AND PURPOSE: New therapeutic interventions for acute ischemic stroke are aimed at improving cerebral blood flow in the first 3 to 6 hours after symptom onset. Single-photon emission-computed tomography (SPECT) performed in the setting of clinical therapeutic trials may give us a better understanding of the physiological response to new forms of treatment and could impact acute management decisions. METHODS: We prospectively studied 15 patients with hemispheric ischemic stroke with SPECT within 6 hours of symptom onset and again at 24 hours. The ischemic defect was assessed in a semiquantitative manner that used computer-generated regions of interest (SPECT graded scale). This measure was correlated with clinical presentation (National Institutes of Health [NIH] Stroke Scale), initial clinical course (change in NIH Stroke Scale), long-term outcome (Barthel Index at 3 months), and complications of cerebral hemorrhage and edema. RESULTS: The severity of the SPECT graded scale on the admission scan correlated with the severity of neurological deficit (admission NIH Stroke Scale) (P < .05) and was positively associated with poor long-term outcome as measured with the Barthel Index (P < .001) and the complications of cerebral hemorrhage and massive cerebral edema (P < .005). In fact, there was a threshold value for the SPECT graded scale above which all patients suffered poor long-term outcome and the complications of cerebral hemorrhage and edema. CONCLUSIONS: The measurement of an ischemic defect using SPECT is a valid assessment of hemispheric stroke severity in the hyperacute setting and may be useful for selecting or stratifying patients in clinical therapeutic trials. PMID- 8362426 TI - The relevance of detecting carotid artery calcification on plain radiograph. AB - BACKGROUND AND PURPOSE: The aim of this study was to determine the potential value of carotid artery calcification observed on plain radiographs in patients referred for carotid angiogram in the diagnosis of carotid artery stenosis. METHODS: One hundred sixty consecutive patients with suspected carotid artery stenosis underwent both plain radiographs of the carotid arteries and digital subtraction angiography of the same vessels. In addition, 108 of these patients also had duplex ultrasound of the same vascular area. The clinical usefulness of the carotid artery calcification was assessed by calculating the likelihood ratios for different test results against results of angiography and duplex ultrasound. RESULTS: There is a statistically significant association between the degrees of calcification and carotid disease as demonstrated by angiography (P = .0001), although positive correlations of the degrees of stenosis and calcification was only fair (Spearman correlation coefficient r = .4). The sensitivity of carotid calcification in detecting clinically significant stenosis assuming any calcification is abnormal was 89% with a specificity of 46%. The likelihood ratios for 50% stenosis by angiography varied from 0.24 (no calcification) to 3.41 (level III) and for 50% stenosis by duplex ultrasound varied from 0.21 (no calcification) to more than 5.87 (level III). Assessments of the degree of calcification based on plain radiographs had excellent reproducibility (all intraclass correlation coefficients were greater than .9). CONCLUSIONS: In this population with a high prevalence of carotid artery disease, there is an association between the presence of carotid calcification and atheromatous disease. If subsequent studies were to show this to apply in the general population, this could be of value in identifying asymptomatic patients at increased risk. PMID- 8362427 TI - Lack of asymmetry of middle cerebral artery blood velocity in unilateral migraine. AB - BACKGROUND AND PURPOSE: A recent transcranial Doppler study found reduced blood velocity in seven patients during migraine attacks in the middle cerebral artery at the headache side. This would implicate vasodilation of the middle cerebral artery in the pathogenesis of headache in migraine. We attempted to confirm this finding. METHODS: We determined blood velocity with transcranial Doppler ultrasonography in the middle cerebral arteries of 51 migraine patients with unilateral headache (5 with aura, 46 without aura) and of 14 patients with bilateral headache, during and outside attacks. During attacks, median time from onset of attack to transcranial Doppler examination was 6 hours (range, 1 to 35 hours). RESULTS: We found no difference between blood velocity at the headache and nonheadache sides nor between blood velocity during and outside attacks. Similar results were obtained in a subgroup of 11 patients who were investigated in the first 4 hours of an attack. There were also no differences between attacks with unilateral or bilateral headache. CONCLUSIONS: We cannot support the hypothesis that migraine is associated with vasodilation of the middle cerebral artery ipsilateral to the headache. PMID- 8362428 TI - Pathogenesis of subcortical hyperintense lesions on magnetic resonance imaging of the brain. Observations in patients undergoing controlled therapeutic internal carotid artery occlusion. AB - BACKGROUND AND PURPOSE: Factors associated with the pathogenesis of subcortical hyperintense lesions on magnetic resonance imaging of the brain are not known. We describe four cases of de novo genesis of subcortical hyperintense lesions in patients undergoing controlled therapeutic internal carotid artery occlusion, and we speculate on associated pathophysiological mechanisms. METHODS: Twelve consecutive patients underwent controlled therapeutic internal carotid artery occlusion for symptomatic giant cerebral aneurysm using the detachable balloon technique under full anticoagulation. Preocclusion (within 2 weeks) and postocclusion (within 6 weeks) magnetic resonance imaging of the brain was performed in eight cases and evaluated for preexisting and new appearance of subcortical hyperintense lesions. RESULTS: There were four instances of de novo genesis of subcortical hyperintense lesions after carotid occlusion. New subcortical hyperintense lesions were ipsilateral to carotid occlusion in every instance and in two cases were associated with ipsilateral hemispheric ischemic symptoms despite anticoagulant therapy. In one instance, there were transient hemispheric symptoms without the appearance of new subcortical hyperintense lesions. Age, vascular risk factors, and preexisting subcortical hyperintense lesions did not appear to predispose patients to de novo genesis of new hyperintensities. CONCLUSIONS: This is the first documentation of de novo genesis of subcortical hyperintense lesions in a controlled setting of hemodynamic ischemic insult. Symptomatic and asymptomatic lesions can be detected in this setting. Anticoagulation does not appear to provide protection from this phenomenon. Careful prospective studies are required to further evaluate risk factors and possible clinical consequences associated with the genesis of new subcortical hyperintense lesions. PMID- 8362429 TI - Silent infarcts in patients with ischemic stroke are related to age and size of the left atrium. AB - BACKGROUND AND PURPOSE: Possible specific risk factors for silent infarcts remain unknown. The aim of this study was to investigate whether risk factors for silent infarcts differ from those for symptomatic infarcts in stroke patients. METHODS: Silent infarcts were defined as asymptomatic infarcts detected on computed tomographic scan in patients free of history of stroke and unrelated to the symptoms and signs of the index stroke. Of 595 consecutive patients with stroke or transient ischemic attacks, 116 (19%) had at least one silent infarct on the first computed tomographic scan performed within 24 hours after onset. They were compared with the 479 remaining patients for cerebrovascular risk factors and for presumed mechanism of stroke by means of the odds ratio method. A discriminant analysis was then performed in the subgroup of 216 patients with ischemic stroke who underwent an exhaustive cardiac and vascular workup. RESULTS: One hundred forty-one silent infarcts (99% confidence interval [CI], 29% to 41%) and 265 symptomatic infarcts (99% CI, 59% to 71%) were subcortical infarcts smaller than 15 mm. Univariate analysis showed that patients with silent infarcts were more likely to be older than 65 years (odds ratio [99% CI], 1.11 to 3.49) and to have left atrial enlargement on echocardiogram (odds ratio [99% CI], 1.02 to 26.70) and leukoaraiosis (odds ratio [99% CI], 1.39 to 4.21). Discriminant analysis found only two independent risk factors for silent infarcts: left atrial enlargement (P = .007) and age older than 65 years (P = .03); leukoaraiosis was not found to be an independent risk factor (P = .86). CONCLUSIONS: Age and left atrial enlargement are the main risk factors for silent infarcts in patients with ischemic stroke or transient ischemic attacks. PMID- 8362430 TI - Cocaine-induced platelet defects. AB - BACKGROUND AND PURPOSE: Numerous studies have demonstrated an association between acute cardiac events, cerebrovascular accidents, and cocaine use. The underlying mechanisms leading to these complications have not been well defined. Using various in vitro model systems, it has been reported that cocaine, up to or greater than an order of magnitude of the lethal dose, causes either inhibitory or proaggregatory effects on platelet function. METHODS: To address these reported discrepancies, we examined the effect of cocaine and its carrier on the activation and aggregation of human platelets in vitro. RESULTS: We found that cocaine inhibited platelet aggregation when platelets were challenged with ADP, collagen, or arachidonic acid. This inhibition was due to a direct effect on fibrinogen binding to the activated platelet. Cocaine also caused the dissociation of preformed platelet aggregates. At these same concentrations, cocaine did not inhibit agonist-mediated increases in cytosolic calcium or inhibit platelet shape change, suggesting that its effect on platelet aggregation was a selective process and not due to a total destruction of platelet function. Interestingly, the organization of the cytoskeleton of activated platelets, a secondary event critical to cell receptor clustering and clot retraction, was disrupted by cocaine treatment. In addition, alterations in platelet protein electrophoretic patterns were observed on preincubation of platelets with cocaine. CONCLUSIONS: We conclude that cocaine may have a direct inhibitory effect on the ability of platelets to participate in thrombus formation. The contribution of this effect as an underlying mechanism of sudden death in cocaine abusers is unknown. PMID- 8362431 TI - Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. BAATAF Investigators. AB - BACKGROUND AND PURPOSE: The Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) demonstrated that low-intensity warfarin anticoagulation can, with safety, sharply reduce the rate of stroke in patients with nonvalvular atrial fibrillation. The beneficial effect of warfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization. METHODS: To assess the effect of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were taking warfarin and 63 were not taking warfarin (control group). RESULTS: The warfarin group had a 71% lower mean F1+2 level than the control group (mean F1+2 of 1.57 nmol/L in the control group compared with a mean of 0.46 nmol/L in the warfarin group; P < .001). F1+2 levels were higher in older subjects but were consistently lower in the warfarin group at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measured. Control patients taking aspirin had F1+2 levels very similar to control patients not taking aspirin (mean of 1.52 nmol/L for control patients on aspirin compared with 1.64 nmol/L for control patients off aspirin; P > .1). CONCLUSIONS: We conclude that prothrombin activation was significantly suppressed in vivo by warfarin but not aspirin among patients in the BAATAF. These findings correlate with the marked reduction in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF. PMID- 8362432 TI - Familial aggregation of stroke. The Framingham Study. AB - BACKGROUND AND PURPOSE: Family history is perceived to be an important risk factor for stroke despite conflicting published data. We examined patterns of familial aggregation of stroke among three generations using data from the Framingham Study. METHODS: Cox proportional hazards analyses, adjusting for known stroke risk factors, were used to examine familial concordance in three groups: (1) members of the original Framingham cohort using reported parental stroke death; (2) members of the Framingham Offspring Study and their parents (members of the original Framingham Study); and (3) sibships within the original Framingham cohort. RESULTS: We found no association between stroke or transient ischemic attack among original cohort members and their reported parental stroke death (n = 4933; relative risk [RR] = 1.07). Using verified cases of parental stroke or transient ischemic attack, the Offspring analyses revealed that both paternal (n = 1762; RR = 2.4; 95% confidence interval [CI], 0.96 to 6.03) and maternal (n = 2074; RR = 1.4; 95% CI, 0.60 to 3.25) histories were associated with an increased risk. Parental history of coronary heart disease was strongly associated with stroke or transient ischemic attack among Offspring Study members (RR = 3.33; 95% CI, 1.27 to 8.72). Sibling history of stroke or transient ischemic attack was not associated with stroke or transient ischemic attack among original cohort members, although a non-statistically significant increased risk associated with sibling history of atherothrombotic brain infarction was observed (RR = 1.8; 95% CI, 0.68 to 4.94). CONCLUSIONS: These analyses suggest that parental history of stroke may be a risk factor for stroke. As more stroke or transient ischemic attack events develop among the Offspring Study members, it will be valuable to reexamine these associations. PMID- 8362433 TI - The prognostic value of admission blood pressure in patients with acute stroke. AB - BACKGROUND AND PURPOSE: Patients with acute stroke are often found to have high blood pressures at hospital admission. Previous studies have shown variable results regarding the prognostic value of high blood pressure in acute stroke. The aim of this study was to investigate the prognostic value of admission blood pressure in a population-based sample of patients with acute stroke. METHODS: Eighty-five patients with intracerebral hemorrhage and 831 with ischemic disease were included in the study. The relations between admission blood pressure and 30 day mortality were studied by logistic regression analyses. RESULTS: High blood pressure in patients with impaired consciousness on hospital admission was significantly related to 30-day mortality in patients with intracerebral hemorrhage (P = .037) and in patients with ischemic disease (P < .0001). In patients without impaired consciousness, high blood pressure at time of admission was not related to increased mortality at 30 days. CONCLUSIONS: High admission blood pressure in alert stroke patients was not related to increased mortality. Stroke patients with impaired consciousness showed higher mortality rates with increasing blood pressure. However, this does not provide a basis for recommending antihypertensive therapy for such patients. PMID- 8362434 TI - Decrease in cerebral blood flow with blood pressure reductions in patients with chronic stroke. AB - BACKGROUND AND PURPOSE: Possible effects of changes in blood pressure on the cerebral circulation were studied in patients with chronic stroke and age-matched nonstroke control subjects at 28 +/- 10 months (mean +/- SD) (range, 18 to 54 months) and 27 +/- 6 months (range, 19 to 44 months), respectively, after the first measurement. METHODS: Cerebral blood flow was measured by the 133Xe inhalation method in 55 patients (mean +/- SD age, 62 +/- 11 years; 39 with brain infarction and 16 with hemorrhage) and 10 control subjects (mean +/- SD age, 61 +/- 9 years). Correlations between changes in cerebral blood flow and blood pressure were evaluated. RESULTS: Among brain infarctions, average cerebral blood flow did not change from the first study; however, changes in cerebral blood flow in each individual were closely related to changes in systolic and mean arterial blood pressures (P < .01 and P < .05, respectively). Of these, in 10 patients with cerebral blood flow decreased more than 15% from the initial levels, systolic and mean arterial blood pressures decreased by 25 +/- 32 mm Hg and 16 +/ 14 mm Hg (P < .05 and P < .005, respectively). In contrast, in 29 patients with unchanged or increased cerebral blood flow, changes in systolic (0 +/- 19 or -2 +/- 12 mm Hg, respectively) and mean arterial blood pressures (3 +/- 22 or -1 +/- 11 mm Hg, respectively) were not significant, and their systolic blood pressure levels were maintained above 110 mm Hg. CONCLUSIONS: Blood pressure importantly correlates with cerebral circulatory changes among patients with chronic brain infarction. Early detection of cerebral hemodynamic changes should be useful for determining the most favorable levels of blood pressure and for selecting appropriate therapy. PMID- 8362435 TI - Decline in US stroke mortality in the era before antihypertensive therapy. AB - BACKGROUND AND PURPOSE: This study was done to determine if reported declines in stroke mortality in the era before antihypertensive therapy are artifactual. METHODS: This study involved analyses of national and state vital statistics data using adjusted and specific rates. RESULTS: Adoption of the third revision of the International List of Causes of Death in 1921 produced an abrupt 6.6% decrease in stroke mortality rates, but otherwise, changes in disease classification systems had little effect on stroke mortality rates. Adoption of the second revision of the joint-cause manual produced a 9.2% drop in stroke death rates, but other revisions of the joint-cause selection rules had little effect. While rates for the expanding group of states in the death registration area progressively declined, rates for fixed component areas remained constant until around 1925 and then declined. Reselection of the underlying cause from aggregate multiple cause data for 1917, 1925, and 1940 using uniform selection rules confirmed a decline after 1925. Correlation analyses of rates of change for stroke and heart disease rates did not support a shift in diagnosis to explain the divergent trends. CONCLUSIONS: The apparent decline in stroke mortality rates before 1925 is an artifact of changes in disease classification systems, joint-cause selection rules, and nonrandom incorporation of states with different mortality rates into the expanding registration area. The decline after 1925 could not be explained by changes in coding systems or joint-cause selection rules or by a shift in diagnosis from stroke to heart disease. PMID- 8362436 TI - Suppressed sympathetic skin response in brain infarction. AB - BACKGROUND AND PURPOSE: Autonomic failure is known to manifest commonly in stroke, but very little attention has been given to various features of sympathetic dysfunction such as sudomotor dysregulation in cerebrovascular diseases. In the present study, our purpose was to assess quantitatively sympathetic reflex activity in brain infarction by measuring the sympathetic skin response. METHODS: We recorded the sympathetic skin response to electric and auditory stimulations simultaneously on both hands in 58 patients with brain infarction and in 36 healthy control subjects. RESULTS: The response amplitudes were significantly decreased and the latencies prolonged in both hemispheral (n = 49) and brain stem (n = 9) infarctions compared with the control subjects. The amplitudes were diminished in both the acute and late phases of infarction, but the latencies were prolonged only in the acute phase. CONCLUSIONS: Sympathetic dysfunction in brain infarction seems to be much more extensive than has previously been thought. In the present study, we have demonstrated impaired sympathetic skin responses, reflecting definite suppression of the reflex activity of the sympathetic nervous system. PMID- 8362437 TI - Screening for neuroborreliosis in patients with stroke. AB - BACKGROUND AND PURPOSE: Borrelia burgdorferi, the etiologic agent of Lyme disease, can cause different neurological manifestations. We studied the prevalence of Lyme neuroborreliosis in patients with stroke. METHODS: During a 1 year period, sera from patients with cerebral thrombosis or transient ischemic attack without cardioembolism were investigated for antibodies against B burgdorferi. RESULTS: One of 281 patients had a positive serum immunoglobulin M titer and 23 of 281 (8%) had positive serum immunoglobulin G titers against B burgdorferi. One of the 24 seropositive patients, with a diagnosis of transient ischemic attack due to dysphasia, had a lymphocytic pleocytosis and intrathecal antibody production against B burgdorferi. The medical history revealed a 9-month period of general and neurological symptoms compatible with Lyme neuroborreliosis before the strokelike incidents. CONCLUSIONS: We conclude that Lyme neuroborreliosis may imitate stroke, but screening for antibodies against B burgdorferi seems to be of little value and may be replaced by a careful medical history. PMID- 8362438 TI - Extracranial vertebral artery pseudoaneurysm presenting as subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: True aneurysms of the extracranial vertebral artery are rare. The usual pathogenesis of aneurysms in this location is either penetrating or blunt trauma with resultant pseudoaneurysm formation. We report a postpartum patient with a presumed traumatic pseudoaneurysm of the extracranial vertebral artery presenting with subarachnoid hemorrhage. CASE DESCRIPTION: A 41-year-old woman had three episodes of neck stiffness 1 month after an uncomplicated vaginal delivery. The last episode, 3 days before admission, was accompanied by intense neck and head pain and paresthesias that extended into the left arm, thumb, and forefinger. RESULTS: Lumbar puncture showed subarachnoid hemorrhage. Angiography revealed a left vertebral artery dissection from C6-7 to C3 with pseudoaneurysm at C5-6. Computed tomography demonstrated impingement of the C6 root at the foramen by this lesion. The lesion was successfully treated by balloon occlusion of the vertebral artery. CONCLUSION: We present a patient with an extracranial vertebral pseudoaneurysm with subarachnoid hemorrhage and cervical root impingement. To our knowledge, this is the first case of such a lesion presenting as subarachnoid hemorrhage. The lesion was successfully treated using endovascular techniques. PMID- 8362439 TI - Intracerebral hemorrhage caused by transmural dissection of the anterior cerebral artery. AB - BACKGROUND AND PURPOSE: Spontaneous dissection of the intracranial carotid artery or its main branches is an unusual condition. CASE DESCRIPTION: A 72-year-old hypertensive woman after an intense nuchal rigidity showed a subarachnoid hemorrhage and an interhemispheric hematoma by computed tomography. The neuropathological study revealed a transmural dissection of the pericallosal artery. CONCLUSIONS: The authors suggest that the dissection origin is an atheromatous plaque that bleeds, producing a dissection plane from the lumen to the adventitial artery. PMID- 8362441 TI - Trials of trials in acute ischemic stroke. The Humana Lecture. PMID- 8362440 TI - Subarachnoid hemorrhage without detectable aneurysm. A review of the causes. AB - BACKGROUND: In 15% to 20% of patients with a spontaneous subarachnoid hemorrhage, no aneurysm is found on the first angiogram. This review emphasizes that this group of patients is in fact heterogeneous and describes the clinical features, pattern of hemorrhage on early computed tomographic (CT) scan, prognosis, and proposed management in the several and distinct subsets of these patients. SUMMARY OF REVIEW: Patients in whom no aneurysm is revealed on the initial angiogram can be subdivided mainly according to the pattern of hemorrhage on an early CT scan. In two thirds of these patients the CT scan shows a perimesencephalic pattern of hemorrhage (ie, blood confined to the cisterns around the midbrain); these patients invariably have a good prognosis, which obviates the need for a second angiogram. Patients with diffuse or anteriorly located blood on CT scan are at risk of rebleeding. In most of these patients the source of hemorrhage is an occult aneurysm, but intracranial artery dissections, dural arteriovenous malformations, mycotic aneurysms, trauma, bleeding disorders, substance abuse, or a cervical origin of the hemorrhage should also be considered. Patients with no blood revealed on an early CT scan but with xanthochromic cerebrospinal fluid are extremely rare. These patients deserve a second reading of the scan for blood in the prepontine cistern, which can be the only site of hemorrhage in perimesencephalic hemorrhage. CONCLUSIONS: The prognosis and management of patients in whom no aneurysm is found on the initial angiogram depends on the pattern of hemorrhage on the initial CT scan. Patients should no longer be designated with the umbrella term "angiogram-negative subarachnoid hemorrhage." PMID- 8362442 TI - Stroke in the young. PMID- 8362443 TI - Ischemic stroke due to or associated with deficiency of coagulation inhibitors? PMID- 8362444 TI - Spontaneous cervical internal carotid dissection presenting with intracerebral hematoma. PMID- 8362445 TI - Red blood cell deformability related to perfusion pressure in cerebral infarction with and without hypertension. PMID- 8362446 TI - Blood pressure changes after stroke: abolishing the white-coat effect. PMID- 8362447 TI - A reliable method to occlude a middle cerebral artery in Wistar rats. PMID- 8362448 TI - Rat models of middle cerebral artery ischemia. PMID- 8362449 TI - Malaria chemosuppression in pregnancy. III. Its effects on the maternal malaria immunity. AB - The malaria immune status of pregnant women participating in a malaria prophylaxis study was assessed using their sera reactivity to the R32tet32 antigen. Supervised prophylaxis started early in pregnancy till delivery. Women randomly received either chloroquine once weekly (CQ), or proguanil daily (PROG), or a combination of the two drugs (CQ + PROG). Blood was collected at enrollment, then after 8, 16, and 24 weeks of prophylaxis. Of the 312 women who received prophylaxis for more than 10 consecutive weeks before delivery, anti-sporozoite antibodies were assayed in 232 at enrollment, 258 after 8 weeks, and 254 after 16 weeks. Titres at enrollment were comparable by parity and the residential area. Antibodies in women of the PROG group who were parasitaemic before the assessments decreased with the increasing number of breakthrough and clinical episodes. The converse was true for antibodies in the CQ and CQ + PROG groups. Group differences in the parasite densities would explain this. Parity and placental malaria did not influence titres significantly. Overall, antibodies of the CQ + PROG group decrease significantly with time, possibly due to its long period of aparasitaemia. This suggested interference with the immune responsiveness of the women. PROG, which was equally efficacious, offers better prophylaxis. PMID- 8362450 TI - Upsurge of malaria-related convulsions in a paediatric emergency room in Nigeria. Consequence of emergence of chloroquine-resistant Plasmodium falciparum. AB - From January through December 1988 the causative factor of each case of childhood seizure seen in the Children's Emergency Room of the University of Calabar Teaching Hospital, Calabar, Nigeria, was prospectively studied with a focus on the relative importance of malaria-related seizures. Of the 134 seizure cases seen, febrile convulsion (FC) formed the majority (55%) with cerebral malaria (CM) as the only major (33%) rival. Other conditions such as meningitis, epilepsy, hypoglycaemia and drug poisoning together (12%) played a minor role. Malaria was the dominant cause (73%) of FC; 81% of these cases did not respond to chloroquine. On comparing the number of cases of CM accumulated in the same unit from 1986, there was a significant increase (P < 0.001) in the proportion of yearly CM admissions from 1986 through 1988. The study confirms the premier position of malaria in the causation of childhood seizures and also suggests a possible upsurge in the prevalence of CM in the environment. This upsurge probably derives from the emergence of chloroquine-resistant Plasmodium falciparum (CRPF) reported in Nigeria which appeared to have been identified in the present study. While more studies are needed to confirm this hypothesis, clinicians in areas of CRPF are alerted about a possible upsurge in CM in their locality. PMID- 8362451 TI - Comparative efficacy of a single 400 mg dose of albendazole or mebendazole in the treatment of nematode infections in children. AB - The relative efficacy of a single 400 mg dose of albendazole or mebendazole in the treatment of nematode infections was assessed in 2- to 9-year-old children living in two different Bolivian rural communities. Both agents were equally very effective (100% cure rate) in treating ascariasis. Albendazole was clearly more active than mebendazole against hookworm infections, both in terms of egg reduction rate (92.8% vs. 62.4%) and cure rate (81.8% vs. 17.2%). As far as trichuriasis is concerned, albendazole produced a higher egg reduction rate than mebendazole (45.7% vs 15%), but a lower cure rate (33.3% vs 60%). Both drugs were well tolerated. PMID- 8362452 TI - Profile of cardiac disease in an out-patient cardiac clinic. AB - The pattern of cardiac disease differs from one region of the world to that of another. This paper aims at providing the profile of heart disease as seen in a Children's Hospital. A total of 468 patients were seen in a follow-up conducted between August 1989 and February 29, 1992. Among these 168 (35.9%) had congenital heart disease (CHD); 278 (59.4%) had rheumatic heart disease (RHD); while 14 (3%) had acquired heart disease of non-rheumatic origin. In patients having RHD, the mitral valve was commonly affected. Ventricular septal defect was the commonest CHD seen followed by patent ductus arteriosus. The results show that RHD is the commonest heart disease seen in a Children's Hospital in Addis Ababa. It is recommended that the issues of school surveillance, better organized secondary prophylaxis need to be addressed. PMID- 8362454 TI - Solitary thyroid nodule in adult Ethiopian patients. Analysis and experience in management in a teaching hospital. AB - Between February 1986 and January 1991, a total of 340 patients with thyroid diseases were seen; 115 (33.8%) had solitary nodules. Of the latter, 28 had toxic adenoma and 87 had euthyroid nodules (M:F = 0.14:7.21); the mean age for the non toxic cases was 32.8 +/- 10.0 years and for the toxic cases, 40.2 +/- 15.2 years. Clinically, the toxic nodules were 0.5 to 6 cm in diameter, cystic in over 36% and firm in the rest; no regional lymph node enlargement was noted. Thyroid scan in 45 (52%) patients showed 38 'cold', 4 hypofunctioning and 3 hyperfunctioning nodules. Ultrasonography in 22 patients (25.3%) revealed 9 cystic and 13 solid nodules, consistent with the clinical finding. Fine needle aspiration biopsy (FNAB) in 61 patients (70.1%) showed 30 cystic, 15 benign, 2 follicular adenoma, 2 Hurtle cell adenoma, 1 papillary carcinoma and 1 thyroiditis. Ten patients were operated; histology confirmed the cytology diagnosis in all but 1 in whom the cytology was benign but histology showed papillary carcinoma. The fine needle aspiration was also useful in the treatment of cystic lesions; hence it should be adopted particularly in areas where there is bed shortage. PMID- 8362453 TI - Surgical management of toxic goitre in Khartoum. AB - Seventy patients with toxic goitre treated surgically in two surgical firms in Khartoum during a 10-years period were studied. Of these patients 62.9% had diffuse goitres, 34.3% nodular and 2.8% hot clinically solitary nodules. The age ranged between 15 and 54 years and the M:F ratio was 1.0:6.7. Ninety per cent of the patients had large size goitres (grade III). Preoperative carbimazole and inderal were found to be superior to other drug combinations. Subtotal thyroidectomy was the standard procedure and no serious postoperative complications were noted. Fifteen patients had postoperative hectic period i.e. fever, headache and tachycardia that responded to temporary inderal and steroids. Surgical treatment of toxic goitre in developing countries could be extended to include more patients since drug availability and patient compliance are minimal. PMID- 8362455 TI - Testicular infarction complicating strangulated inguinal herniae in Nigerian children. AB - Between 1985 and 1990 30 children were operated on for strangulated inguinal herniae in the University of Benin Teaching Hospital, Benin City, Nigeria. Six of the children (20%) had testicular infarction secondary to the strangulated hernia. Half of the children with infarcted testes had viable bowel at operation. The surgeon dealing with African children with strangulated herniae needs to be sensitised to this condition and the possibility that the testis may well be infarcted before the intestines. PMID- 8362456 TI - Identification of the ligamentum teres hepatis by ultrasound and the clinical importance of its thickening. AB - In a survey of 100 healthy persons or patients without any obvious abdominal pathology the ligamentum teres hepatis (LTH) was detected by ultrasound in 87%. The mean diameter of the normal LTH was determined as 4.5 mm (range 3-6 mm). In a second group of 131 patients with obvious abdominal pathology, the LTH could be identified in 82 patients (63%). Among these, the LTH was thickened (diameter > or = 7 mm) with a mean diameter of 11.9 mm (range 7-33 mm) in 47 patients (57%). Twenty-six patients had uniform or smooth thickening, 21 patients had nodular thickening. Smooth thickening was a feature mainly seen in cases of portal hypertension with a lumen demonstrable in one-third of them. Nodular thickening was mainly associated with metastasising intra-abdominal malignancy. However, smooth or nodular thickening of the LTH may also be caused by non-pathological accumulation of fat within the ligament. PMID- 8362457 TI - Multiple lentigines syndrome in a Nigerian family. AB - Three cases of the multiple lentigines syndrome are reported in a Nigerian family, involving a father and two of his children. The major abnormalities in this syndrome include: multiple lentigines, cardiac defects, genitourinary malformations, neurological deficits, growth retardation, cephalofacial dysmorphism and a family history consistent with an autosomal dominant mode of inheritance. We hereby report these cases in whom the main features are multiple lentigines, ocular hypertelorism, electrocardiographic defects and a pattern consistent with an autosomal dominant mode of inheritance. PMID- 8362458 TI - Epileptic fit: the most dramatic sign of tuberous sclerosis. AB - This rare disease of dominant inheritance is described with the symptom triad of epilepsy, mental deficiency (oligophrenia) and adenoma sebaceum. The skin manifestation may be manifest in the first year, but the parents seek the help of the physician only when the dramatic symptom of convulsion occurs. PMID- 8362459 TI - Lifetime of reusable syringes and needles. A field study. AB - For planning of supplies and costs it is important for an immunization unit to know how many times reusable syringes and needles can be used. A field study found that BCG syringes, which had their rubber seals replaced once, could be used at least 150 times, and DPT syringes more than 200 times even when sterilized in tap water with a hardness of 88 mg calciumoxyde per liter. Needles could be used 100 times and when resharpened several times even more. PMID- 8362460 TI - Sarcoptes scabiei in animals spreading to man. AB - An outbreak of Sarcoptes scabiei in animals was observed from mid-November 1991 to mid-December 1991 in two adjacent villages, Fewgram and Nurpur, in Birbhum District, West Bengal State, India, starting from goats to cattle, then to sheep and even to dogs. Nineteen goats and one cattle died of manage infection. The infection spread to man in the last week of December 1991, and affected forty-two human beings, tending and rearing animals. The animals treated with deltamenthrin (synthetic pyrethroid) and amitraz (triazapentadiene) were completely cured. In man, the disease seemed to be self-limited in some cases and 2% hexachlorobenzene was successfully used for treatment of the others. The outbreak was effectively controlled in March 1992. PMID- 8362461 TI - Scarcity of radiodiagnostic services in developing countries. PMID- 8362462 TI - Imaging equipment for small hospitals. AB - Imaging equipment is expensive and the correct choice is difficult. Guidelines are provided. The proper choice will result in high quality x-rays and ultrasound scans even where electrical power is unreliable and no technical staff are available. PMID- 8362463 TI - Evaluation of methods for treating obstructive lung disease. Minireview based on a doctoral thesis. PMID- 8362464 TI - In vitro screening of putative compounds inducing fetal porcine pancreatic beta cell differentiation: implications for cell transplantation in insulin-dependent diabetes mellitus. AB - Successful transplantation of fetal pancreatic beta-cells to diabetic recipients requires that differentiation of the immature beta-cells is achieved. Animal experiments have shown that this can occur in vivo, but it would be desirable to induce beta-cell maturation in vitro prior to transplantation. For that purpose the effect of several putative inducers of beta-cell differentiation and/or replication in explant cultures of fetal porcine pancreatic islet-like cell clusters (ICC) were investigated. Initial screening experiments indicated that dexamethasone (DEX; 200 ng/ml) and sodium butyrate (BUT; 2 mM) might promote beta cell differentiation as evidenced by increased insulin/DNA contents in the ICC. In subsequent experiments these two substances, and also nicotinamide (NIC; 10 mM) which previously has been found to promote fetal beta-cell differentiation, were added alone or in combinations to the basal control medium consisting of RPMI 1640 + 1% human serum. All three test agents alone or in combinations increased the insulin content/DNA of the ICC compared with that of the control group. The combination of NIC+DEX increased the insulin mRNA levels of the ICC. No significant stimulation of insulin release was observed in any test group after short-term incubation with high glucose alone. Addition of 5 mM theophylline to high glucose stimulation, however, increased the insulin secretion in most groups of ICC. Finally, ICC in groups of about 600, which had developed in the presence of NIC or NIC+DEX, were transplanted under the kidney capsule of alloxan-diabetic nude mice. However, neither the time for reversal of diabetes (4 weeks) nor the amount of insulin secretion during perfusion from the grafted ICC were further affected by adding DEX to the NIC supplemented medium. The marked increase of the insulin content of the ICC cultured with DEX supplementation, appeared transient and was not manifested after transplantation. In conclusion, the present study demonstrated that some compounds can stimulate porcine fetal beta-cells in an in vitro system, but in order to attain terminal differentiation of the beta-cells including glucose-sensitive insulin secretion, longer observation periods might be required than used herein. Alternatively, an in vivo environment like that after transplantation is mandatory for this process. PMID- 8362466 TI - A protocol for structured observation of motor performance in preterm and term infants. AB - A new protocol for structured observation of motor performance has been designed for assessment of the progress and quality of motor development in preterm and term infants. A detailed scale of motor development based on the present knowledge of motor development in healthy term infants has been constructed. The motor performance is observed in each part of the infant's body in the supine and prone positions and in the whole body with the infant sitting, standing and during locomotion, and is evaluated in relation to defined levels of motor performance. If the quality of motor performance is optimal for a certain level, no deviation is noted. Any deviation from the motor performance described in the protocol for the level in question is graded as suspected or clear and classified by type. All observations are recorded on videotape for documentation. In a study of inter- and intraobserver agreement, such recordings from 17 infants were reassessed on two occasions more than one year apart. The interobserver agreement ranged between 73 and 87% and the intraobserver consistency between 77 and 88%. The protocol is currently being used in a follow-up study. PMID- 8362465 TI - Carbon-13 NMR studies of alpha-elastin. AB - NMR investigations of model protein of elastic fibre is presented. Detailed conformation of alpha-elastin polypeptide chain is discussed by comparison with the conformation of synthetic repeat peptides of elastin. Amino acid composition of alpha-elastin obtained from C-13 NMR spectra correlates with the results of sequencing of tropoelastin. PMID- 8362467 TI - A protocol for structured observation of motor performance in preterm and term infants. Interobserver agreement and intraobserver consistency. AB - A new protocol for structured observation of motor performance, for use both in term and preterm infants, has been tested regarding interobserver agreement and intraobserver consistency. Ten different motor items are assessed concerning the developmental level as described in the protocol. Any deviations from the description of the level are noted. The two main observers twice reassessed video recordings of 17 infants who had primarily been assessed by them both in an ongoing follow-up study. The two observers arrived at the same level of development in 75% of the observed items at the first reassessment and in 81% at the second, and agreed concerning deviation in 73 and 79% of the observations at the two reassessments, respectively. Each observer arrived at the same level of development at all three assessments in 62% of the observed items. Thus when used by these two observers the protocol has an acceptable degree of interobserver agreement and intraobserver consistency. PMID- 8362468 TI - Relations between mixed venous oxygen saturation and hemodynamic variables in patients subjected to abdominal aortic aneurysm surgery and in patients with septic shock. AB - In order to study if oxygen saturation in mixed venous blood (SvO2) could be used as a marker for heart performance, oxygen delivery (DO2) or consumption (VO2) in critically ill patients 134 hemodynamic measurements were performed by a thermodilution pulmonary catheter in 23 patients after abdominal aortic aneurysm surgery. These data were compared to 200 measurements performed in 30 patients with septic shock. When analysed on an individual basis SvO2 was only closely related to DO2 or VO2 in a minority of the patients. Neither could SvO2 be used as a reliable marker for heart rate, hemoglobin concentration, stroke volume or cardiac index. On the other hand SvO2 was found to be an excellent marker for oxygen extraction (OER) in both groups of patients (median r = 0.98. p < 0.0001). In conclusion, the present study shows that SvO2 could not be used as a reliable marker for the important hemodynamic variables CI, DO2 or VO2 in critically ill patients. However, SvO2 was found to be an excellent marker for OER. PMID- 8362469 TI - Enteric neuropathy in horses with grass sickness. AB - The degeneration of enteric neurones has been recorded in grass sickness, but the distribution of the lesions in the gut and their possible relationship with the severity of the clinical signs has not been established. Samples obtained from 11 anatomically defined sites along the gastrointestinal tract of eight control horses without gastrointestinal disease, five horses with acute grass sickness and three horses with chronic grass sickness were examined histologically. The organisation of the enteric ganglia was similar to that in other large mammalian species. Minor exceptions included the presence of fundic mucosal nerve cell bodies and blood vessels within submucosal ganglia. All the horses with grass sickness had severe enteric neuropathy, widespread in the acute cases but localised to the distal small intestine in the chronic cases. These neuronal lesions are consistent with, and may explain the intractable gastrointestinal propulsive deficit that characterises grass sickness. PMID- 8362470 TI - Demonstration of co-resistance of Haemonchus contortus to ivermectin and moxidectin. AB - Studies were conducted to determine whether organisms which are resistant to ivermectin are also resistant to moxidectin. The mechanisms of action of moxidectin and ivermectin were compared by measuring the changes in membrane conductance they induced in leg muscle fibres of the common shore crab (Pachygrapsus crassipes) by using standard micro-electrode techniques. Meriones unguiculatus (jirds) were infected with ivermectin-resistant or -susceptible strains of Haemonchus contortus, treated with moxidectin or ivermectin at a dose which routinely clears more than 98 per cent of the susceptible strain, and examined for parasite clearance. The results showed that moxidectin induced a rapid loss of membrane resistance in the muscle preparation, and that the effect was almost 50 per cent reversible with the chloride channel-blocker picrotoxinin; this pattern of activity is qualitatively similar to that of ivermectin. In the jird model, moxidectin achieved a clearance of only < or = 47.2 per cent against ivermectin-resistant H contortus at a dose which invariably clears > or = 98 per cent of an ivermectin-susceptible strain. These results indicate that moxidectin and ivermectin share a common mechanism of action, and that organisms that are resistant to ivermectin are also likely to be resistant to moxidectin. PMID- 8362471 TI - Clinical disease associated with Trypanosoma theileri infection in a calf in Ireland. AB - A four-month-old calf had a clinical history of pyrexia, anaemia, weight loss and behavioural abnormality. Clinical examination revealed evidence of regenerative anaemia and a lymphocytosis which was characterised by a relatively large B cell population. The calf deteriorated clinically while under observation and its prescapular and prefemoral lymph nodes became enlarged. Examination of a blood smear revealed the presence of a large number of circulating Trypanasoma theileri. Serological examination showed the presence of the invariant, stage specific, trypanosome surface antigen, ISG70 and antibodies against ISG70. ISG70 was first identified in the bloodstream forms of Trypanosoma brucei and has not previously been found in T theileri. Clinical recovery was associated with an increase in packed cell volume, a decrease in the levels of circulating anti ISG70 antibodies and the complete disappearance of circulating ISG70. PMID- 8362472 TI - Aspergillus niger isolated in an outbreak of rhinitis in rats. PMID- 8362473 TI - Efficacy of morantel citrate against benzimidazole resistant field strains of Ostertagia circumcincta. PMID- 8362474 TI - Possible basis of adverse reactions to vaccination against equine influenza. PMID- 8362475 TI - Incidence of hypomagnesaemia. PMID- 8362476 TI - Severe foul-in-the-foot in dairy cattle. PMID- 8362477 TI - Solar haemorrhages in dairy cattle. PMID- 8362478 TI - Canine dysautonomia: another case report. PMID- 8362480 TI - Elizabethan collars and plastic bags. PMID- 8362479 TI - Anaemia in a dog. PMID- 8362481 TI - Homoeopathic nosode questionnaire. PMID- 8362482 TI - Role of acid mucopolysaccharides in the depletion of clenbuterol. PMID- 8362483 TI - Effects of abattoir and slaughter handling systems on stress indicators in pig blood. AB - Pigs from four farms were slaughtered at two abattoirs, each with two slaughter handling systems. Pigs at abattoir X were electrically stunned, either in a floor pen holding five pigs or in a race-restrainer. At abattoir Y pigs were stunned either in a floor pen holding five pigs or in a dip-lift carbon dioxide stunner. At exsanguination, 96 blood samples (24/farm) were collected from pigs slaughtered through each slaughter handling system (384 samples in total). Serum samples were analysed for cortisol, creatine phosphokinase (CPK) lactate dehydrogenase (LDH) and LDH-isoenzymes. There were no significant differences between the systems at abattoir X. At abattoir Y, pigs slaughtered through the floor pen system had higher levels of LDH-5 (39.84 +/- 1.39 per cent of total LDH vs 34.76 +/- 1.21 per cent, P < 0.05) indicating greater skeletal muscle damage in the floor pen. Pigs at abattoir Y had higher mean serum levels of CPK than pigs at abattoir X (3.63 log10 U/litre vs 3.41 log10 U/litre, 0.03 sed, P < 0.001), higher total LDH activities (1269.5 U/litre vs 922.8 U/litre, P < 0.001) and higher cortisol concentrations (1.70 log10 ng/ml vs 1.51 log10 ng/ml, P < 0.001). These differences suggested that the levels of physical and psychological stress were higher at abattoir Y. PMID- 8362484 TI - Typing of feline calicivirus isolates from different clinical groups by virus neutralisation tests. AB - One hundred and thirteen isolates of feline calicivirus originating from seven different clinical groups were typed by virus neutralisation tests using eight different cat antisera. The clinical groups comprised 'healthy' cats, cases of acute oral/respiratory disease, chronic stomatitis, acute febrile lameness syndrome, vaccine reactions (clinical disease seen within 21 days of vaccination) and vaccine breakdowns (clinical disease seen more than 21 days after but within one year of vaccination). Isolates from the vaccine reaction cases were grouped into those associated with acute oral/respiratory disease alone and those associated with the lameness syndrome, and the latter group was further subdivided according to the vaccine used. Two groups appeared significantly different from others with some of the antisera. Thus the lameness vaccine reaction isolates associated with vaccine B were significantly different from the isolates from all the other clinical groups, including other lameness isolates, with a number of the antisera. In addition, the chronic stomatitis isolates were significantly different from those from the 'healthy' and the acute oral/respiratory disease groups with one or two of the antisera. Eighty-five to 88 per cent of the isolates were neutralised by antisera raised against F9 or F9 like vaccine strains at a dilution of 1 in 2. Twenty antibody units of such antisera neutralised 42 to 80 per cent of the isolates. A bivalent antiserum raised against a vaccine F9 strain and field strain LS015 neutralised 96 per cent of the isolates at a dilution of 1 in 2, and 20 antibody units neutralised 68 per cent of isolates. Antisera to field strain F65 neutralised all the remaining isolates at a dilution of 1 in 2 and 44 per cent of the remaining isolates at a dilution of 20 antibody units. Therefore, strains LS015 and F65 may be of use in the production of a polyvalent feline calicivirus vaccine, together with the widely used strain F9. PMID- 8362485 TI - Occurrence of spiral-shaped bacteria in gastric biopsies of dogs and cats. PMID- 8362486 TI - Heterospermic insemination of cattle using three bulls of the same breed. PMID- 8362487 TI - EC standards. PMID- 8362488 TI - Orthopaedic surgery in wild animals. PMID- 8362489 TI - Cryptosporidium species in ostriches. PMID- 8362490 TI - Mushroom poisoning in a dog. PMID- 8362491 TI - Diagnosis of grass sickness by ileal biopsy. AB - Ileal biopsies were obtained from 18 horses with grass sickness, 15 horses with other alimentary disease and three horses without gastrointestinal disease. Samples of small intestine were also obtained from nine cases of obstruction due to small intestinal strangulation. Histological examination revealed that severe enteric neuropathy in the absence of other significant morphological changes was confined to the horses with grass sickness. PMID- 8362492 TI - Comparison of outer-membrane fractions of Serpulina (Treponema) hyodysenteriae. AB - Sarkosyl-insoluble fractions (outer-membrane proteins) and endoflagella (EF) fractions of Serpulina hyodysenteriae serotypes 1-7 were examined for protein differences using SDS-PAGE. Both the outer-membrane proteins (OMP) and endoflagella were also examined for antigenicity using porcine sera from acutely infected and convalescent swine. Seven major staining proteins were resolved in outer-membrane enriched fractions ranging in molecular weight between 42 and 32 kDa. A comparison of purified EF to OMP from serotype 1 and 2 isolates of Serpulina hyodysenteriae demonstrated that six of the seven OMP were actually EF. Sera from swine with acute swine dysentery identified only a portion of the proteins from both preparations. In contrast, immune sera from convalescent swine identified all the proteins in the OMP and EF preparations as well as an additional 16 kDa carbohydrate antigen. PMID- 8362493 TI - A cytotoxicity test for the detection of Campylobacter jejuni toxin. AB - A 7-h 51Cr-release cytotoxicity assay has been developed to detect the presence of Campylobacter jejuni toxin in the culture supernatant. Some of the culture supernatants have cytotoxic effects against labeled chicken lymphocytes, while some others do not have this effect. There is no direct correlation between the pathogenicity of the organisms and the presence of the toxin. The supernatant of C. jejuni retains its cytotoxicity after heating at 100 degrees C for 10 min.; therefore, it is a heat stable toxin. PMID- 8362495 TI - Species-specific recombinant DNA probes for Mycoplasma meleagridis. AB - Two recombinant DNA probes (pMM-2 and pMM-13) were isolated from a Mycoplasma meleagridis strain 17529 genomic library prepared in plasmid pUC8, and Escherichia coli strain JM83. In dot blot assays, 32P-labeled pMM-13 with a DNA insert of 3.5 kbp, hybridized with 18 isolates of M. meleagridis but not with 16 other known species of avian mycoplasmas. Except for weaker signals on hybridization with the M. meleagridis cultures, pMM-2 with an DNA insert of 0.85 kbp, showed a similar reaction pattern. The minimal concentration of M. meleagridis strain 17529 chromosomal DNA that pMM-13 and pMM-2 detected were 1 and 8 ng, respectively. Neither probe hybridized with chromosomal DNA of M. gallisepticum strain S6, M. synoviae strain WVU-1853, or M. iowae strain I-695 at concentration of 256 ng. PMID- 8362494 TI - Comparison of ovine abortion and non-abortion isolates of Chlamydia psittaci using inclusion morphology, polyacrylamide gel electrophoresis, restriction endonuclease analysis and reactivity with monoclonal antibodies. AB - Twelve reference and four Northern Ireland ovine Chlamydia psittaci isolates including ovine abortion, faecal, conjunctivitis and arthritis isolates were compared. Inclusion morphology was shown to provide a useful means of differentiating the abortion and the non-abortion isolates studied. Identical SDS PAGE polypeptide profiles were produced by the ovine abortion isolates. The polypeptide profiles of the non-abortion isolates were similar to one another and clearly distinct from the abortion isolate profiles. The restriction endonuclease profiles of the abortion isolates were remarkably similar whereas different profiles were produced by most of the non-abortion isolates. Monoclonal antibodies were prepared and characterized. A number of these reacted with all the isolates of chlamydia tested. Three mAbs reacted exclusively with the ovine abortion isolates while four mAbs reacted exclusively with a number of the faecal isolates. PMID- 8362496 TI - Borrelia burgdorferi infection in dairy cows, rodents, and birds from four Wisconsin dairy farms. AB - A combination of culture and subsequent spirochete identification with the polymerase chain reaction technique was used to identify cows, rodents, and birds infected with Borrelia burgdorferi. Animals were trapped on four Wisconsin dairy farms during the summer of 1990. Farms 1 and 2 were located in counties nonendemic for Lyme disease and Farms 3 and 4 were located in counties endemic for Lyme disease. The results of the rodent and bird samples were as follows given as the number yielding organisms number tested: Farm 1, 1/17 Mus musculus and 2/52 Peromyscus domesticus; Farm 2, 4/49 M. musculus, 1/2 P. maniculatus, 1/1 P. leucopus, and 1/35 P. domesticus; Farm 3, 0/27 M. musculus, 0/5 P. leucopus, 0/12 P. maniculatus and, 3/58 P. domesticus; and Farm 4, 1/24 M. musculus, 2/19 P. leucopus, 1/12 Microtus pennsylvanicus, and 0/17 P. domesticus. One P. leucopus and one M. musculus from Farm 2 were pregnant and fetal tissues from both were positive. Cow blood sample results were as follows: Farm 1, 7/47 in July, and 2/45 in August; Farm 2, 0/28 in August and 0/23 in October; Farm 3, 0/13 in July and 1/18 in August 29; and Farm 4, 3/45 in August. Ticks were found on rodents on Farm 4 and on one bird on Farm 3. Spirochetemic cows, rodents, and birds were found in non-Lyme endemic counties suggesting that alternate modes of transmission other than by ticks may be important. Transplacental transmission was shown in M. musculus and P. leucopus. PMID- 8362497 TI - Differences in protein expression of Haemophilus somnus grown under conditions of iron-restriction. AB - Outer membrane protein profiles were compared in 14 H. somnus strains isolated from brain and lung lesions as well as from the genital tract of asymptomatic carriers during in vitro growth under iron-restricted conditions. Ethylenediamine di-O-hydroxyphenyl acetic acid (EDDA) was used to obtain iron-restricted conditions in media used for this study. The outer membrane protein profiles were studied by the discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoretic system (SDS-PAGE), and the proteins were stained with silver or transferred to nitrocellulose sheets and western blots conducted. Growth under iron-restricted conditions resulted in the induction of outer membrane proteins in most H. somnus strains examined. Studies also indicated differences among H. somnus strains in the number of induced proteins and their molecular weights but the results did not indicate a specific relationship between these strain dependent differences and tissue trophism. Western blot analysis revealed a high degree of immunological relatedness among strains of H. somnus in their iron regulated proteins. However, hyperimmune serum used in these assays failed to recognize certain iron-regulated proteins expressed by some H. somnus strains, a finding which may have important implications for the induction of protective immunity in cattle against this bovine pathogen. PMID- 8362498 TI - Instrumentation of exercising thoroughbreds to determine blood gas tensions and acid-base status. AB - A device was constructed of easily obtained medical supplies, and hardware and could be used to obtain multiple arterial samples when manually triggered. The right carotid arteries in five normal horses were surgically elevated, thereby permitting percutaneous cannulation. Each horse was galloped on a 1.6-km test track at approximately 500 m/min, and the rider triggered the mechanism at each 0.4-km mark. Each horse underwent 10 test gallops, and a mean and standard error was determined for each sampling mark including preexercise and postexercise samples. The results indicated that horses ridden under the aforementioned conditions became acidemic and hypoxic. PMID- 8362499 TI - Blood gas tensions, acid-base status, heart rates, and venous profiles in exercising horses with laryngeal hemiplegia before and after corrective surgery. AB - The physiologic effects of exercise were studied in four horses with complete laryngeal hemiplegia. Right carotid arteries were surgically elevated to a subcutaneous position for percutaneous catheterization. Each horse was fitted with a device designed to obtain multiple arterial samples while the horse was exercised over a 1.6-km course. After each horse completed 10 test gallops, the laryngeal hemiplegia was treated using a laryngeal prothesis and ventriculectomy. The horses were then reconditioned, and the exercise test and sampling were repeated. Horses with laryngeal hemiplegia became acidotic, hypoxic, and hypercapnic compared to normal horses. Surgical treatment improved blood gas and acid-base status, but the values were not equivalent to those in normal horses similarly tested. PMID- 8362500 TI - Marsupialization of umbilical vein abscesses with involvement of the liver in 13 calves. AB - Omphalophlebitis with liver involvement was diagnosed by ultrasonography in 13 calves. In the initial surgical procedure, the infected umbilical vein was marsupialized by cranial translocation in a median celiotomy and was flushed daily until healing occurred. In a second surgical procedure, the contracted umbilical vein was removed. Nine calves were clinically healthy after treatment. One had reformation of two abscesses because of inadequate post-surgical treatment. One calf was euthanatized because of an intussusception of the small intestine, and two calves had adverse reactions and developed septic shock when some of the lavage fluid, which was applied under pressure, entered the systemic circulation. It was concluded that umbilical vein abscesses should not be flushed under pressure in calves younger than 2 months of age. The principal advantages of cranial translocation of the umbilical vein in a median celiotomy are that only one abdominal incision is required and that the infected umbilical vein tissue does not have to be passed intraabdominally to a paramedian position. PMID- 8362501 TI - Primary repair of abomasal fistulae resulting from right paramedian abomasopexy in eight adult dairy cattle. AB - Abomasal fistulae resulting from right paramedian abomasopexy in eight adult dairy cattle were treated by primary closure of the abdominal wall after surgical resection of the fistulae. The median elapsed time from the abomasopexy to recognition of fistula formation was 16 days (range, 10 to 90 days). All cows had normal electrolyte values, and five cows had mildly increased base excess values (range = 4.0 to 7.8 mEq/L). Surgery was performed with the cows in dorsal recumbency using general anesthesia. The fistulated tissue was resected and the abomasum and body wall were closed primarily. One or two layers of appositional sutures using #2 or #3 polyglactin 910 were used to close the body wall. Mean surgical time was 2.2 hours (range, 1.8 to 2.9 hours). Two cows were lost to follow-up. Five of the remaining six cows returned to production (range, 5 to 30 months). Primary closure of the abdominal wall should be considered in the surgical repair of abomasal fistulae in cows that do not have diffuse peritonitis. PMID- 8362502 TI - Ex vivo biomechanics of Kirschner-Ehmer external skeletal fixation applied to canine tibiae. AB - The purpose of this study was to determine the respective contribution of each of the following parameters to the compressive, bending, and torsional rigidity of the Kirschner-Ehmer (KE) external fixation splint as applied to canine tibiae with an osteotomy gap: bilateral versus unilateral splints; increasing the number of fixation pins; altering the diameter of fixation pins and side bars; decreasing side bar distances from the bone; increasing pin separation distances in each pin group; decreasing distances between pin groups; altering pin clamp orientation; and altering side bar conformation. Bilateral splints were 100% (mean) stiffer than unilateral splints, with stiffness enhanced to the greatest extent in mediolateral bending and torsion. Increasing pin numbers stiffened both bilateral (mean, 41%; 8 versus 4) and unilateral splints (mean, 14%; 8 versus 4). Medium KE splints were 85% (mean) stiffer than small KE splints. Decreasing side bar distances to the bone from 1.5 cm to 1.0 cm to 0.5 cm increased stiffness of both bilateral and unilateral splints by a mean of 13% to 35%. Widening pin spacing from 1.67 cm to 2.5 cm increased stiffness in craniocaudal bending only (56% increase, bilateral splints; 73% increase, unilateral splints). Decreasing the distance between pin groups from 5.84 cm to 2.5 cm increased stiffness in torsion between 23% (unilateral splints) and 45% (bilateral splints) and decreased stiffness of unilateral splints by 29% in craniocaudal bending. Altering pin clamp configuration so that the bolts of the clamp were inside the side bar rather than outside the side bar increased stiffness in axial compression only (73% increase, bilateral splints; 54% increase, unilateral splints). Conforming the lateral side bar to the tibiae increased only axial compressive stiffness by 77% but was no different than placing the clamps inside the side bars of an unconformed bilateral splint. These results quantify the relative importance of specific parameters affecting KE splint rigidity as applied to unstable fractures in the dog. PMID- 8362503 TI - In vitro loss of tensile strength and elasticity of five absorbable suture materials in sterile and infected canine urine. AB - The loss of breaking strength and elasticity of five absorbable suture materials (polydioxanone [PDS-II], polyglycolic acid [PGA], polyglactin 910 [PG-910], polyglyconate [GTMC], and chromic gut) after in vitro incubation in sterile, Escherichia coli- and Proteus mirabilis-inoculated canine urine was studied. Biomechanical testing, in a controlled environment, was performed during the 28 day study period. Polydioxanone and chromic gut retained greater than 90% of their original strengths after 28 days of incubation in sterile urine and 87% of original strengths in E. coli-inoculated urine. Polyglyconate retained 24% and 18% of original strength, respectively, after incubation in sterile and E. coli inoculated urine for 28 days. Polyglycolic acid and PG-910 retained less than 30% of original strength in sterile urine and only 7% in E. coli-inoculated urine after 21 days of incubation. In P. mirabilis-inoculated urine, loss of tensile strength and elongation was significant for all suture materials. Polyglycolic acid and PG-910 lost all strength after 24 hours of incubation. Polydioxanone lost all strength after 7 days of incubation, whereas GTMC retained 19% at day 7. Chromic gut retained 78% at day 7 and 16% after 21 days of incubation, however, the absence of normal phagocytic destruction of chromic gut in this in vitro study may have artificially elevated these values. In sterile urine with chemically modified pH, loss of strength and elongation was greater in alkaline urine than in neutral or acidic urine for all types of suture materials. PMID- 8362505 TI - Oxalate nephrosis and renal sclerosis after renal transplantation in a cat. AB - A 10-year-old castrated domestic shorthair cat received two renal allografts, 14 days apart, for the treatment of chronic renal failure. Oxalate nephrosis developed in both allografts, and they became nonfunctional. During the transplantation period, the cat was not exposed to exogenous sources of oxalate, and there was no evidence of primary type 2 hyperoxaluria before surgery. Urologic surgery, in particular renal transplantation, has been identified as a factor that can precipitate renal failure in human patients with decompensated renal function and hyperoxaluria. If hyperoxaluria was present before surgery in this cat, it was most likely caused by increased absorption or decreased metabolism of dietary oxalate. PMID- 8362504 TI - Clinical, biochemical, and hematologic evaluation of normal dogs after administration of rabbit anti-dog thymocyte serum. AB - Renal allografting is the only long-term alternative to euthanasia in dogs with end-stage kidney disease. The purpose of this study was to determine the clinical, biochemical, and hematologic effects of rabbit anti-dog thymocyte serum (RADTS) in normal dogs and to develop a safe and practical route of administration before its use in an allograft immunosuppressive protocol. Thirteen mongrel dogs were divided into three groups; each received RADTS subcutaneously, intramuscularly, or intravenously. The inflammation and pain associated with subcutaneous administration was unacceptable. A significant (p < or = .05) leukopenia and lymphopenia developed in all dogs, regardless of the route of administration of RADTS. Thrombocytopenia was a consistent finding after intravenous administration and with high doses given intramuscularly. Both the intravenous and intramuscular routes were well tolerated by all dogs with minimal or no discomfort. Serum creatinine was unchanged, whereas serum alanine aminotransferase activity increased in one dog. There were no histologic changes in any of the kidneys examined. PMID- 8362506 TI - Cecal-colic volvulus in two dogs. AB - Cecal-colic volvulus was confirmed by surgery in two dogs. Both dogs were intact, male Great Danes. The clinical and diagnostic findings were not specific for large bowel volvulus. Clinical signs included peracute to acute onset of vomiting, mild abdominal distention and pain, lack of feces, and tenesmus. Abdominal radiographs demonstrated severe dilatation of bowel loops in both dogs. One dog survived. PMID- 8362507 TI - Parenteral anticholinergics in dogs with normal and elevated intraocular pressure. AB - Dogs given parenteral anticholinergic drugs have been thought to be at risk for development or exacerbation of elevated intraocular pressure (IOP). In a randomized, blinded, placebo-controlled study, we evaluated the effect of intramuscular glycopyrrolate (0.01 mg/kg) on pupil diameter and IOP in unanesthetized normal dogs. Treatment with glycopyrrolate did not change pupil diameter or IOP from baseline, nor were there differences between glycopyrrolate and saline-treated (control) dogs. In addition, the authors retrospectively reviewed the medical records of 2,828 dogs undergoing general anesthesia between April 1987 and September 1990 to determine if there was an association between parenteral anticholinergic medication and postanesthetic elevation in IOP. The authors also determined the frequency of bradycardia requiring anticholinergic therapy during anesthesia in dogs with glaucoma. Of the 2,828 cases reviewed, the records of 46 dogs coded for glaucoma were examined in detail. The 46 dogs underwent 62 episodes of anesthesia, with 23 episodes including exposure to an anticholinergic drug. An increase in IOP from preanesthetic to postanesthetic measurement occurred in three dogs. One of these dogs received anticholinergic medication for bradycardia during anesthesia. The postanesthetic elevation in IOP in this dog was probably not drug related. Preanesthetic anticholinergic administration did not affect the incidence of anticholinergic administration for bradycardia during the anesthetic episode. Anticholinergic therapy during anesthesia was more frequent when the preanesthetic medication included an opiate drug. These studies do not indicate an association between parenteral anticholinergic administration and elevations in IOP. PMID- 8362508 TI - Endotracheal tube displacement during cervical manipulation in the dog. AB - A retrospective study was performed to identify positional changes of endotracheal tubes (ETT) during cervical spine radiography in 153 dogs. Three neck positions were identified: traction, hyperextension, and flexion. A properly placed ETT was defined as having the caudal tip of the tube located between the caudal half of the fourth cervical (C) vertebra (C4) and the caudal half of C7. In the traction position, before neck flexion and extension, the caudal tip of 13% of ETT were located caudal to C7, and one tube was in the endobronchial position at the seventh thoracic (T) vertebra (T7). In the hyperextended position, 60% of ETT moved cranially. The average distance moved was 0.6 vertebral spaces. In the flexed position, all ETT moved caudally. The average distance moved was 3.5 vertebral spaces, with 81.8% of ETT located caudal to C7 and seven tubes in endobronchial positions. Endotracheal tube occlusion caused by kinking at the atlanto-occipital joint was seen in four dogs during flexion of the neck. Based on this study, ETT position should be monitored during cervical manipulation. PMID- 8362510 TI - How far shall we go in the predonation selection of blood donors to safeguard patients for blood-transfusion-related infections? PMID- 8362509 TI - Intraosseous cannulation and drug administration for induction of anesthesia in chickens. AB - Twenty-four chickens were randomly assigned to one of three treatments (ketamine, 30 mg/kg; thiopental, 20 mg/kg; saline, 0.8 mL). Baseline data (heart rate, respiratory rate, systolic blood pressure, and cloacal temperature) were recorded before ulnar intraosseous cannulation and administration of drug treatment and for 30 minutes after administration. One investigator, unaware of the treatment administered, assessed the reaction to cannulation, number of attempts per cannulation, reaction to injection, time to induction and recovery, and quality of induction and recovery. Respiratory rate increased significantly (p < .05) from baseline after thiopental. Other parameters did not vary within groups or between groups. Most birds did not react or had a mild reaction to cannulation and injection, and on average fewer than two attempts were necessary. Quality of recovery was significantly (p < .05) better after thiopental. Time to recovery was significantly (p < .05) shorter after thiopental. No major histopathologic changes were noted in bone marrow samples from the injection site. This study demonstrates that the intraosseous route may be used to induce anesthesia in chickens, and that minimal changes in the variables studied were produced by ketamine and thiopental. PMID- 8362511 TI - Blood transfusion and immunomodulation: a possible mechanism. AB - To induce an immunogenic response in vivo, an antigen-presenting (stimulator) cell must present both antigen-specific (class II MHC) and an accessory signal to the CD4 T cell. Failure to express the accessory signal has been shown in vitro to induce a state of specific unresponsiveness (anergy) in the T cell. We have shown that although stimulator cells in blood continue to express class II MHC molecules during refrigerated storage, their ability to present the accessory signal diminishes, reaching zero in all units tested by about 13 days. This implies that blood in excess of 2 weeks old should not alloimmunize but could induce some degree of immunosuppression. UV-B irradiation and, to a lesser extent, gamma-irradiation, were also shown to inhibit expression of the accessory signal by stimulator cells in blood. PMID- 8362512 TI - Ultraviolet irradiation inhibits killer-target cell interaction. AB - The effects of ultraviolet (UV) irradiation on cell-mediated cytolysis were examined in order to clarify the inhibitory mechanisms of allosensitization by UV irradiation. UV-B-irradiated target cells (Sa; an Epstein-Barr virus-transformed B cell line) exhibited more resistance against alloreactive cytotoxic T lymphocytes (CTL) than mitomycin C (MMC)-treated target cells. In the conjugate formation assay, UV-B-irradiated target cells showed a considerably lower binding to alloreactive CTL than MMC-treated target cells. UV-B irradiation induced a reduction of HLA-class I, -DR, CD54 (ICAM-1) and CD58 (LFA-3) expression on target cells. However, it does not seem to contribute to the inhibition of cell adhesion induced by UV-B irradiation because a similar reduction of cell surface antigens was observed in MMC-treated target cells. Number of cells capped with anti-HLA-class I, -DR, CD54 or CD58 monoclonal antibody were markedly reduced by UV-B irradiation compared to that by MMC treatment. These findings suggest the possibility that the inhibition of cell adhesion between UV-B-irradiated Sa target cells and alloreactive CTL is due to the impaired mobility of cell surface antigens which will affect the early process of cell-mediated cytolysis. PMID- 8362513 TI - Transfusion-transmitted Yersinia enterocolitica infection. Protection through buffy coat removal and failure of the bacteria to grow in platelet-rich or platelet-poor plasma. AB - In a previous study, removal of white blood cells (WBC), by filtration 5 h after deliberate contamination of whole blood with a type 0:3 strain of Yersinia enterocolitica, was shown to be an effective way of avoiding bacterial growth in red blood cells (RBC) during storage. In the present study the Opti-System technique was used to remove the buffy coat from whole blood, leaving 10-20% of the original number of WBC in the RBC preparation. In one series of experiments, all of 4 units of RBC suspension, from which buffy coats were removed 2 h after inoculation of 112 colony-forming units (cfu) per ml of Y. enterocolitica, became Yersinia-free, while abundant bacterial growth occurred in all of 4 units where RBC suspension and buffy coat had been recombined. In a second series of 10 experiments, with an inoculum of 80 cfu/ml, no growth was found in platelet-poor plasma stored for 42 days at 4 degrees C. Five out of 10 RBC suspensions in SAGM additive solution remained Yersinia-free throughout a 6-week storage period; 4 of these 10 units showing growth of Yersinia after 4 weeks and 5 after 6 weeks. In the buffy coats bacterial growth was found in 1 out of 10 units after 1 week, 4 after 2 weeks, and in all of 10 units after 4 weeks. In 2 control experiments with WBC-reduced RBC inoculated with the same bacterial dose, growth started within 24 h and was abundant after 1 week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362514 TI - Human monoclonal anti-D-induced clearance of human D-positive red cells in a chimpanzee model. AB - Two human monoclonal anti-Rh0(D) antibodies, one IgG1, and one IgG3, were tested for their ability to clear human D-positive red blood cells (RBCs) from chimpanzee circulation. Human RBCs (phenotype A1, R1r) from 1 donor were radiolabelled with chromium 51 and injected into 4 chimpanzees. One day later the control animal received isotonic saline whereas 2 animals received 400 micrograms of purified human monoclonal anti-D, either IgG1 or IgG3. The remaining animal received both antibodies together (200 micrograms of IgG1 and 200 micrograms of IgG3). Both individual antibody-mediated clearance of human D-positive cells and synergy was not observed when both antibodies were used in combination. IgG1 was slightly more effective than IgG3. This animal model is a suitable alternative for conducting in vivo experiments in human beings, especially at the preclinical study phase of monoclonal anti-D antibodies. PMID- 8362515 TI - Evidence for the protective effect of maternal FcR-blocking IgG alloantibodies HLA-DR in Rh D-haemolytic disease of the newborn. AB - In cases of Rh D alloimmunization, strong results in the antibody-dependent cell mediated cytotoxicity (ADCC) assay (> 80% lysis as compared to that of the standard anti-D serum) are indicative of severe hemolytic disease to occur in the newborn (HDN). However, discrepant cases were found in which the maternal anti-D gave strong ADCC results and the newborns had no or only mild hemolysis. In the majority of these cases the mother had produced monocyte-reactive IgG alloantibodies, mostly with HLA-DR specificity. Such antibodies may be capable of blocking FcR-mediated functions of the fetal MPS, and it has been postulated that they inhibit destruction of anti-D-sensitized red cells. We here describe 2 families in which such discrepancies were noticed. In 1 family, in spite of ADCC results of > 80%, the Rh D-positive second child was born without signs of hemolysis. However, the Rh D-positive third child suffered from very severe hemolytic disease. The mother had produced monocyte-reactive HLA-DR antibodies in the second pregnancy which, however, did not react with the cells of the third child. In the other family, the severely Rh D-alloimmunized mother had lost her fourth child because of intrauterine death due to HDN. The Rh D-positive fifth child was born with only mild HDN and only in this pregnancy had the mother produced such antibodies. These 2 case histories give further evidence that maternal monocyte-reactive alloantibodies, in both these cases directed against HLA-DR antigens, can protect the Rh D-positive child against hemolytic disease in case of severe Rh D alloimmunization. PMID- 8362516 TI - Protection against Rh D-haemolytic disease of the newborn by a diminished transport of maternal IgG to the fetus. AB - IgG present in the circulation of newborn infants is predominantly of maternal origin. In cases of severe Rh D alloimmunization, the maternal anti-D anti-bodies may lead to Rh D-haemolytic disease of the newborn. However, an impaired placental transport of maternal IgG could be associated with the protection of the fetus/newborn against haemolytic disease as shown in this case report. PMID- 8362517 TI - Plasma and red-cell glycolipid patterns of Le(a+b+) and Le(a+b-) Polynesians as further evidence of the weak secretor gene Se(w). AB - Monoclonal antibodies and thin-layer chromatography were used to study the unusual erythrocyte Lewis phenotypes found in healthy Polynesians. A single monoclonal anti-Leb reagent 073 (clone LM129) was found which could detect Leb antigen on the Polynesian erythrocytes of samples that were unreactive with various polyclonal and monoclonal anti-Leb reagents. Glycolipid fractions prepared from the plasma and erythrocytes of selected Polynesian samples of red cell Le(a-b-), Le(a+b-) and Le(a+b+) phenotypes were found to have Leb glycolipids. The Leb antigen in some individuals is so weakly expressed that it is undetectable by routine erythrocyte phenotyping. Unusually large glycolipids bearing the Leb epitope were also found in some Polynesian samples, although the contribution of these novel glycolipids to phenotyping is unclear. The inability to detect Leb by routine methods and the presence of novel structures can be partially explained in terms of the presence of a weak secretor gene Se(w). PMID- 8362518 TI - Confirmation of anti-ELO as a cause of haemolytic disease of the newborn. PMID- 8362519 TI - Anti-HIV in Spanish blood donations from 1988 to 1991. Spanish Study Group on HIV blood donations screening. PMID- 8362520 TI - Dose of anti-D immunoglobulin for the prevention of RhD immunisation after RhD incompatible platelet transfusions. PMID- 8362521 TI - Observations on Australia antigen in Japanese. Vox Sang 1968:15:374-85. PMID- 8362522 TI - Immunofixation electrophoresis: a technique for the study of protein polymorphism. Vox Sang 1969:17:445-52. AB - A technique is described which allows direct visualization of individual proteins in mixtures by specific antiserum after electrophoresis. By minimizing diffusion it permits rapid, direct, and clear detection of genetic polymorphism and 'conversion' of proteins in the complement and coagulation systems. PMID- 8362523 TI - ISBT Working Party on Terminology for Red Cell Surface Antigens. Sao Paulo report. PMID- 8362524 TI - WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty third report. PMID- 8362525 TI - Is preoperative radiographic localization of islet cell tumors in patients with insulinoma necessary? AB - Preoperative localization tests [sonography, computed tomography, angiography, percutaneous transhepatic portal venous sampling for insulin radioimmunoassay (PTP)] have a sensitivity of 60% to 90% in cases of organic hyperinsulinism. In all publications, however, the sensitivity of intraoperative localization, 75% to 100%, is distinctly higher. With the exception of PTP, all tumors that can be identified by preoperative localization can also be detected using palpation or intraoperative sonography. Preoperative localization diagnosis is therefore not absolutely necessary prior to primary operation in the case of organic hyperinsulinism. It is requested by many surgeons because: (1) only a few clinics have extensive experience with patients with an organic hyperinsulinism; (2) only a few clinics have extensive experience with intraoperative sonography; (3) the accuracy of palpation is improved following appropriate preoperative localization; and (4) in rare cases, the results of a PTP influence the operative procedure. PMID- 8362526 TI - Use of selective arterial secretin injection test to guide surgery in patients with Zollinger-Ellison syndrome. AB - It is often difficult to localize gastrinomas in patients with Zollinger-Ellison syndrome (ZES). We have developed a new useful method, the selective arterial secretin injection test (SASI test), for localizing gastrinomas in patients with ZES. The SASI test first determines the arteries feeding the gastrinomas and then locates the gastrinomas. In 12 patients with ZES, the SASI test clearly localized the gastrinomas, while results obtained with computed tomography or portal venous blood sampling had a positive predictability of less than 10%. Following localization with the SASI test, curative resection of gastrinomas was successfully performed on 7 patients who consented to the operation. Each of 3 patients had one duodenal submucosal microgastrinoma and one or more metastatic lymph node; the other 4 patients had 2 to 10 microgastrinomas or large gastrinomas in the duodenum or the pancreas. All 7 patients, who exhibited negative responses with a postoperative secretin test, have been completely cured from 3 months to 4 years postoperatively. The usefulness of the SASI test for preoperative evaluation is demonstrated by the fact that it gives a 100% positive predictability rate as well as a 100% negative predictability rate. Hence the SASI test precisely locates functioning gastrinomas. PMID- 8362527 TI - Intraarterial calcium stimulation test for detection of insulinomas. AB - Occult insulinomas are adenomas not visualized by routine preoperative imaging studies, including ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and arteriography. Reliance for detecting occult insulinomas has been placed on portal venous sampling (PVS), a sensitive (> 75%) but invasive procedure that requires considerable experience to enable sampling of small veins about the pancreatic head. For the past 2 years we have attempted to localize insulinomas by stimulating the release of insulin with a selective intraarterial injection of calcium gluconate and sampling for insulin gradients in the hepatic veins. This study replaces PVS by indicating the region of the pancreas within which the tumor lies, although, like PVS, it does not directly visualize the tumor. Our experience in 9 patients with surgically proved insulinomas is reviewed, comparing the results with PVS as well as with US, CT, MRI, and arteriography. PMID- 8362528 TI - Surgical treatment of the Zollinger-Ellison syndrome. AB - A consecutive series of patients with Zollinger-Ellison syndrome (ZES) is reported. A total of 53 cases were diagnosed, treated, and followed by one department during the period 1971-1990. Curative surgery was considered in all cases after suppression of acid secretion and after localization of the tumors. Exploratory laparotomy was not employed. Of the 53 patients 13 (24%) died from metastatic gastrinoma during the study. Tumors were ultimately located in 31 of the patients, and 21 of these patients were operated. A total of 12 patients (21%) were cured. The best results were obtained after Whipple pancreaticoduodenectomy in patients with small tumors located after percutaneous transhepatic portography with blood sampling for gastrin assay. In this group 9 of 10 operated patients were cured. Multiple endocrine neoplasia type I did not seem to preclude curative resection. The findings support an aggressive attitude toward local diagnosis and surgical treatment in ZES patients, but they also stress the need for improvements in methods for localizing tumors. PMID- 8362530 TI - Experimental study of pylorus and pyloric vagus preserving gastrectomy. AB - In an attempt to prevent the sequelae of conventional gastrectomy, such as rapid gastric emptying, dumping syndrome, intestinal content reflux, indigestion, and poor absorption, we have devised the pylorus and pyloric vagus preserving gastrectomy (PPVPG). Experimenting on 48 dogs, we found theoretic grounds for using our design and obtained the desired effects--retaining the merits of conventional subtotal resection of the stomach, with acidity reduction, while avoiding the above-mentioned complications. PMID- 8362529 TI - Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome. AB - During the last 5 years important advances have occurred in the control of gastric acid hypersecretion in Zollinger-Ellison syndrome (ZES). The increased availability of potent gastric acid antisecretory agents such as histamine H2 receptor antagonists and more recently the H+K(+)-ATPase inhibitors such as omeprazole and lansoprazole have made it possible to medically control acid secretion in all patients. Increased understanding of the variation in antisecretory drug dosage between individual patients has led to identification of criteria to ensure effective antisecretory control and to the recognition of subgroups of patients who require special monitoring. Effective regimens for parenteral antisecretory control during surgery have been established. The importance of parathyroidectomy in patients with multiple endocrine neoplasia type I with ZES and the possible usefulness of highly selective vagotomy have been investigated. We review here the new data that led to increased understanding in each of these areas from our studies and studies by others. PMID- 8362531 TI - Exogenous growth hormone: effects on the catabolic response to surgically produced acute stress and on postoperative immune function. AB - The first purpose of the present prospective randomized study was to determine if the protein catabolic response after operation could be restrained by administration of hypocaloric parenteral nutrition (HPN) plus human growth hormone (hGH). Our second aim was to determine if the administration of hGH could improve the systemic host defenses, thereby reducing the risk of infection. We performed a placebo-controlled randomized double-blind trial in 180 patients after elective cholecystectomy with or without choledochoduodenostomy (placebo = control group, n = 93; hGH-treated group, n = 87). The results obtained in this study show that positive nitrogen balance can be achieved during the postoperative period from the first 24 hours onward, with a combination of HPN support (1.0-1.5 g protein/kg/day and 900 kcal/day) together with the administration of small doses (8 IU) of hGH. The potassium balance tended to follow the same positive balance as the nitrogen balance. Our study shows that in the control group, treated only with HPN, a significant decrease in serum levels of some acute-phase proteins (retinol-binding protein, transferrin, prealbumin), albumin, total proteins, and immunoglobulins occurs by the 5th postoperative day. In the GH group the values of all the above-mentioned proteins do not change or tend to rise if compared to preoperative levels. In the GH-treated group liver function appeared to improve at the start of the study. GH and somatomedin C levels were similar in the two groups and had not changed significantly in the control group by the 5th postoperative day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362532 TI - Laparoscopic cholecystectomy: a minor abdominal trauma? AB - Clinical observations following laparoscopic surgery indicate a shorter period of postoperative ileus than after conventional surgery. The aim of our study was to verify disorders of postoperative motility of the small intestine by means of implanted electrodes after laparoscopic and conventional cholecystectomy (CHE) in an animal model. Four weeks after implantation of three electrodes on the jejunum, CHE was performed laparoscopically in 5 dogs and in an additional 5 dogs by laparotomy. Independent of the type of operation, normal motility (especially the migrating motility complex) was abolished during the early postoperative period. Electrical activity was characterized by the basic electrical rhythm. Time to the occurrence of the first postoperative activity front, indicating restoration of motility, varied significantly depending on the type of operation: It was 5.5 +/- 1.0 hours after laparoscopic CHE and 46 +/- 5 hours after conventional CHE. These results support the hypothesis that small peritoneal incisions and less manipulation of the intestine during laparoscopic surgery result in reduced abdominal trauma. PMID- 8362533 TI - Pulmonary function after cholecystectomy performed through Kocher's incision, a mini-incision, and laparoscopy. AB - Comparative pulmonary function after cholecystectomy performed through Kocher's incision, a mini-incision, and laparoscopy was evaluated. Forty-five patients were randomly and prospectively divided into three groups of 15 each, depending on the surgical access employed. Forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and forced expiratory flow at 25% to 75% (FEF25-75%) were determined 1 to 3 days before and 16 to 24 hours after cholecystectomy. The percent reduction of FVC (p = 0.0170), FEV1 (p = 0.0191), and FEF25-75% (p = 0.0045) was smaller after laparoscopic cholecystectomy than after Kocher's incision cholecystectomy. The percent reduction of FVC (p = 0.0170) was smaller after mini-incision cholecystectomy than after Kocher's incision cholecystectomy. There was no difference in the FEV1 (p = 0.0971) or FEF25-75% (p = 0.2058) between these two groups. FEF25-75% was significantly less impaired in the laparoscopic group than in the mini-incision group (p = 0.0327). No difference between these two groups was found in FVC (p = 0.5755) or FEV1 (p = 0.3952). It is concluded that postoperative pulmonary function is less impaired after laparoscopic cholecystectomy than after either mini-incision or Kocher's incision cholecystectomy. PMID- 8362534 TI - Bile duct injury during laparoscopic cholecystectomy: mechanism of injury, prevention, and management. AB - Although several studies have shown a low incidence of bile duct injuries during laparoscopic cholecystectomy, concerns remain because of the sustained increase in the number of referrals for biliary reconstruction after the procedure. Twenty one patients have been referred to our institution because of major bile duct injuries after laparoscopic cholecystectomy. The injury was recognized during the laparoscopic procedure in only 6 of the 21 (29%). Nineteen patients underwent hepaticojejunostomy at least once, one patient required hepaticojejunostomy and repair of a choledochoduodenal fistula, and one patient needed repair of a biliary colonic fistula. Hepaticojejunostomy above the bifurcation was required in 10 patients (50%), at the bifurcation in 3, and below the bifurcation in 7. Nine of the eleven patients in whom the initial repair was performed at the local hospital presented with early stricture (median 7 months). The common denominator of the development of bile duct injuries during laparoscopic cholecystectomy is the failure to identify the structures of the triangle of Calot. Specific steps during laparoscopic cholecystectomy to avoid bile duct injuries are described. Expertise in hepatobiliary surgery appears to optimize results of biliary reconstruction. PMID- 8362536 TI - John Hunter, 1728-1793. PMID- 8362535 TI - Management of bile duct injuries and strictures following cholecystectomy. AB - During 7057 conventional cholecystectomies (1972-1991), 16 bile duct injuries occurred, amounting to a risk of 0.22%. A total of 1022 laparoscopic cholecystectomies were performed without such a complication since April 1990. In a retrospective study, 64 patients (16 of our patients and 48 referrals) with an injury or stricture due to conventional cholecystectomy were investigated. In 14 of our 16 patients the injury was recognized and immediately repaired with a good long-term result of 93%, including one successful repair of a subsequent stricture. Two cases of unrecognized injury were managed by nonoperative means. The group of 48 referred patients comprised 10 early postoperative complications (21%) and 38 strictures after an "uneventful" cholecystectomy. Of the 64 total patients, 10 (16%) underwent nonoperative treatment, and 54 required surgery. The mean follow-up period after surgery was 7.4 +/- 4.9 years. Most cases (93%) were repaired by bilioenteric anastomosis (i.e., foremost hepaticojejunostomy) with an 18% restricture rate. Including second and third repairs for restricture, a total of 60 operations (14 primary and 46 secondary reconstructions) were performed without hospital mortality. A good long-term result after stricture repair was achieved in 75% of the patients, whereas 17% had a poor outcome owing to restricture or death (10% had related mortality within 10 years). The other 8% had a moderate result due to recurrent cholangitis. Thus immediate repair of a bile duct injury offers the better chance of a favorable prognosis compared to secondary stricture repair. PMID- 8362538 TI - [Allocation and fairness problems in current medicine exemplified by transplantation medicine]. PMID- 8362537 TI - [Ethical values in the transition of health systems]. PMID- 8362539 TI - [Economic regulation and ethical conflicts in general practice]. PMID- 8362540 TI - [Economic treatment waiver and patient selection as a legal problem]. PMID- 8362542 TI - [The contribution of medical ethics to cost reduction in health care]. PMID- 8362541 TI - [Between self determination and outside control--on the role of the physician in health care]. PMID- 8362543 TI - [Intestinal helminthiasis]. PMID- 8362544 TI - [Value of prognostic factors in prostate cancer]. PMID- 8362545 TI - [Diagnostic errors in kidney and urinary tract findings]. PMID- 8362546 TI - [From general practice of an expert assessment service: abdominal pain always need extensive examination]. PMID- 8362547 TI - [A case from general practice (11): a young man with angina pectoris]. PMID- 8362548 TI - [Carl Arnold Ruge--the "Meesta"]. PMID- 8362549 TI - Dedicated to Ezras Asratovich Asratian for the 90th anniversary of his birth. PMID- 8362550 TI - Development of conditioned reflexes theory in E. A. Asratyan's school (90 years from the birthday). PMID- 8362551 TI - [The dynamics of individual preference in the probability and value of reinforcement in the development of experimental neurosis]. AB - After single and repeated negative emotiogenic (neuroticizing) influences in phlegmatics and cholerics in a situation with different probability and value of reinforcement a change of behaviour strategy takes place--from the preference of a reinforcement of higher probability but worse quality to that of low probability but valuable. Strategy of behaviour of sanguinics and melancholics remains unchanged with the preference of a reinforcement of low probability but better quality. The greatest sensibility to negative emotiogenic influence (a conflict situation) was established in phlegmatics and the lowest sensibility--in sanguinics. The obtained data are discussed from the positions of P. V. Simonov's concept on the four brain macrostructures (the hippocampus, amygdala, hypothalamus, and the frontal cortex) in the aspect of significance of the level of their functioning and interaction for the pathogenesis of neuroses. PMID- 8362553 TI - [The effect of diazepam on behavior and hippocampal electrical activity in the dog]. PMID- 8362552 TI - [The "circular" interaction of the signal, motivational and emotiogenic structures in food and defensive (classical and instrumental) conditioned reflexes]. AB - In experiments with dogs was shown the role of motivational and emotional structures of the hypothalamus in reproduction of the adaptive motor reaction both in classical and instrumental conditioned reflexes (alimentary and defensive). Change of parameters of electrostimulation gave a possibility to activate differentially the motivational, emotional negative, and emotional positive structures of the hypothalamus. Electrostimulation of the motivational structures reproduced alimentary but not defensive adaptive motor reaction and decreased the threshold of the motor reaction which was used as a signal during classical alimentary conditioning. Electrostimulation of the emotional negative structures reproduced defensive adaptive reaction and inhibited alimentary unconditioned response. Elaboration of the avoidance of the stimulation of the lateral hypothalamus was a proof for the activation of the emotional negative structures. Electrostimulation of the emotional positive structures which was used as an unconditioned stimulus during self-stimulation conditioning reproduced neither defensive nor alimentary conditioned response. PMID- 8362554 TI - [The autonomic component of food and defensive conditioned reflexes acquired to bursts of light and electrostimulation of the limbic structures and the basal ganglia]. AB - Alimentary and defensive instrumental conditioned responses (CRs) to light flashes, electrical stimulation of the dorsal hippocampus and the nucleus caudatus were elaborated in seven dogs. These CRs were tested by electrostimulation of the limbic structures and the basal ganglia. Motor and vegetative components of CRs were compared. If there occurred an instrumental movement during the conditioned stimulus the heart rate increased with a high probability. If there were no movement the heart rate increase approached the level of significance only in five dogs of seven. The heart rate always increased in the positive generalization tests while in the negative ones the heart rate either decreased or increased to a lesser degree. PMID- 8362555 TI - [The functional role of the motor area of the cortex in the acquisition of escape reactions in dogs]. AB - The model of escape conditioning similar to classical (pavlovian) was proposed. During shock application to the hind limb (a conditioned stimulus) the ipsilateral foreleg flexion was elicited by a stimulation of the motor cortex (an unconditioned stimulus); both stimuli were turned off in the course of the forepaw lifting. Such uniform pairings resulted in elaboration of a reaction of the foreleg flexion in response to the shock. Prolonging the shock by 3 s after the cortical stimulation led to a rapid extinction of the acquired response. So a possibility to instrumentalize movements elicited by stimulation of the motor cortex (MI) was proved. This is in argument in favour of an assumption that the established "instrumental" connection (drive-motor structures) can be addressed directly to the motor cortex. PMID- 8362556 TI - [Frontal-hypothalamic interaction in cats in the realization of a free choice of reinforcement]. AB - In experiments with four cats instrumental delayed responses with a reinforcement of different quality were elaborated by the method of "active choice" the time of delay of the motor reaction serving as a signal of quality of the reinforcement. Individually varying ability to chose the quality of the reinforcement was used for classification of typological properties of cats (self-control and impulsiveness). Multiunit activity was recorded from the motor cortex and the lateral nucleus of the hypothalamus. Analysis of interneuronal connections was made by the cross-correlation method. Identified connections between hypothalamic and motor cortex neurons were found in 13-18% of all the possible connections. The interneuronal cortical-hypothalamic relationships were characterized by temporal delays from 0 to 100 ms. The analogy was found in distribution curves of temporal delays in all the time ranges investigated for the neurons of the hypothalamic-motor coordination in each group of cats in spite of the manifestation of preferred or alternative conditioned reactions. The number of identified connections of hypothalamus-motor cortex coordination with temporal delays up to 30 ms was significantly higher for the cats working in impulsiveness paradigm. At the same time, there were significantly more identified connections of hypothalamus-motor cortex coordination with temporal delays of 60-100 ms in cats demonstrating self-control. The question is discussed on the role of the hypothalamus-motor cortex relationships in the choice of behaviour strategy and typological characteristics of cats. PMID- 8362557 TI - [Hypothalamic neurons and defensive reflexes]. AB - Identified groups of neurons in positive (the lateral hypothalamic area, the lateral preoptic area) and negative (the ventromedial hypothalamus) emotional regions were examined under the different levels of food motivation and emotionally positive and negative intracranial stimulation. The responses of the neurons in classical and operant conditioning were different. This difference was manifested in tonic (during location of the animal into the chamber) and phasic alterations of neuronal activity and at certain stages of conditioned reflex performance. During classical conditioning were revealed the reciprocal relations in unit activity of the positive and negative emotional structures. During the operant reflex more complicated pattern of reactions was observed being connected with realization of a necessity of removing from the negative influences. During defensive reflex in the cases of classical conditioning and avoidance reaction reinforcement was related with engaging the negative emotional mechanisms while in the course of escape reaction the positive emotional mechanism being engaged. PMID- 8362558 TI - [The correlation between the changes in synaptic efficiency and cellular excitability in the acquisition of a conditioned reflex analog]. AB - By calculating correlation coefficients was revealed the positive linear correlation between the conditioned changes of direct and indirect components of the pyramidal tract response pointing to a correlation between changes of synaptic efficiency and coincident shifts of cellular excitability. Coincidence of the maximal value of this connection with that of cellular excitability dependent on the activation of the lateral hypothalamus points to the role of this subcortical motivational structure in starting intracellular reactions leading to a formation of a common molecular substrate underlying interaction of the membrane and synaptic mechanisms. Precedence of the maximal manifestation of this interaction to the highest increase of synaptic efficiency testifies to the contribution of this process to the manifestation of the basic mechanism of conditioned reflex. PMID- 8362559 TI - [The nerve centers of the emotions]. AB - The participation and the role of the brain formations in the genesis of emotional reactions of higher animals and man are discussed according to E.A. Asratian's concept of the nervous centre as a complex of brain structures, situated in different areas of the central nervous system, comprising the total morpho-functional unity and realizing a definite specific function. The data are given testifying that the frontal and temporal areas of the neocortex, hippocampus, amygdala and hypothalamus are correspondingly connected with reflecting-estimating, compensatory, transferring and reinforcing functions of emotions. The reinforcing function is phylogenetically the most ancient. It is connected with solution of the universal behavioural task of maximization minimization of the appeared emotion, striving for "to" or "from". Replacing and transferring functions have been formed later, while reflecting-estimating one is the most young. It namely provides the wealth and diversity of emotions, based on complicated vital, social and cognitive needs. Such succession coincides with the evolution of the corresponding brain formations, with their phylogenetic age. PMID- 8362560 TI - [The bioelectrical activity of the human brain in representatives of different temperamental types]. AB - The goal of the paper was to reveal integral characteristics of temperament related to the peculiarities of interhemispheric interaction. With this aim in view, the types of temperament were studied in persons with different professional orientation. The temperament type with a "strong" nervous system and a higher capacity for work was shown to be characterized by a higher level of synchronization of biopotentials in the frontal regions of the brain, and that between the distant brain areas (frontal and occipital ones) as well as by more intensive activation of the right hemisphere in the process of mental work. This type of temperament was more often found among the persons whose profession was connected with artistic creative activity. PMID- 8362561 TI - [Asynchronous asymmetry (sexual and lateral differentiation--a consequence of asynchronous evolution)]. AB - In the paper is presented a unified interpretation of sex differentiation and lateral asymmetry as asynchronous evolution. The operative subsystems, i.e. the male and the left hemisphere of the brain evolutionize earlier than the conservative ones, i.e. the female and the right hemisphere. New functions appear at first in males and after many generations they are transferred to females. The leading centers of their control are at first originated in the left hemisphere, then they are translocated to the right one. The criterion for functions localization in the hemisphere is their evolutionary age: new functions are controlled by the left hemisphere, old functions by the right one. Therefore the left hemisphere is socio-cultural, ethnic, the right one is biological, special. The theory explains from a single standpoint the phenomena of sex, handedness, nervous crossover, as well as many know facts, and predicts the new ones. PMID- 8362562 TI - [A structural analysis of the behavior of cynomolgus macaques under the conditions of their group housing in cages]. AB - The conceptual basis of the present study is an idea on systemic interdependence of neurobiological phenomena (at any level of their occurrence, including the integral behavioural level). Characteristic peculiarities of probable organization of natural behavioural activity of Java monkeys (M. irus) kept in cages in monosexual groups were studied by recording ethograms with subsequent computer analysis. By ranging probabilities of transitions between separate behavioural acts and classifying them by motivational categories, were described the probable etiological structures of individual behaviour and intraspecific interaction in a group. Only in case of intraspecific interaction these behavioural structures were characterized by a high variability of the probability of their occurrence in different observations. The data obtained were considered from the position of biological significance of the probabilities of transitions between separate specific behavioural patterns in the organization of the whole behavioural activity. PMID- 8362563 TI - [The modification of the intraspecific behavior of male rats raised in isolation with different variants of interaction with related animals]. AB - It was found that intraspecific behaviour of male rats having been transformed in consequence of breeding under the conditions of social isolation could be modified afterwards by an experience of social contacts. Long-term keeping the isolatedly bred rats with their mates in adulthood decreases the level of intraspecific sociability but does not affect the relatively high level of aggression of the animals under study. On the contrary, the short-term periodic social contacts with the mates in a situation of competition for water decrease only the level of aggression but not that of intraspecific sociability. However, in any case the transformations of the species-typical ritual of aggressive behaviour in consequence of early isolation are steady and are not corrected by later social contacts. PMID- 8362564 TI - [The role of glucose in facilitating defensive reactions during feeding in the edible snail Helix lucorum]. AB - The glucose role in a regulation of defense responses during feeding behaviour was studied in the snail Helix lucorum. It was found that 15-20 min after the beginning of the food intake the foot withdrawal response evoked by a train of electrical pulses was facilitated up to 20-30%. At the same time glucose concentration in the haemolymph increased from 0.5 +/- 0.1 mM in the starved molluscs to 0.9 +/- 0.5 mM in the snails at 20-25 min of eating. In the food satiated snails and 30-90 min after the food intake the glucose level in the haemolymph was 1.6 +/- 0.5 mM. It was shown that 0.5 ml glucose solution (5 mM) injected into the mantle cavity also facilitated the foot withdrawal defense response in the fastened snail, whereas injection of 2.5 mM or 10 mM glucose solutions were ineffective. These data support a supposition that glucose in one of the endogenous factors involved in regulation of defense behaviour during feeding in snails. PMID- 8362565 TI - [The spectral characteristics of the electrical activity of the cortex and subcortex in the dominant of thirst]. AB - Dominant of thirst was elaborated in water-deprived rabbits by sound stimuli. One judged about the formation of the dominant by a regular appearance of the swallowing or chewing reactions in response to testing stimulations. Spectral analysis of the brain electrical activity revealed a generalized lowering of the spectral power of the potentials of the studied cortical and subcortical areas all over the analysed frequency range. The paraventricular nucleus, the lateral preoptic and anterior hypothalamic areas, in spectrograms of which an increase of estimations in the slow frequency range took place, were an exception. Analysis of the electrical activity recorded at different moments of the dominant manifestation (the tonic state of dominant and that immediately before the summation movement) showed that to each of these dominant states corresponded an appropriate maximum in the theta-frequency range, probably reflecting different levels of motivational-emotional excitation. PMID- 8362566 TI - [An electrographic analysis of the dynamic change in the functional state of the rat brain after destruction of the locus coeruleus]. AB - Bilateral destruction of the Locus coeruleus in rats was carried out by means of 6-hydroxydopamine injections. Sham-operated animals served as control ones. Electrical activity was recorded in the region of the Locus coeruleus, the dorsal hippocampus, and in the caudatus-putamen complex. Beginning from the second week after surgery in experimental rats was observed a generalization of the theta rhythm (7-9 Hz) in electrical activity of the Locus coeruleus, hippocampus and the caudatus-putamen complex during orienting-exploratory activity. At the same time such a rhythm was enhanced in animals with motor and orienting-exploratory agitation. In comparison to the sham-operated animals there were no changes in expression in the electrical activity of the subcortical structures of the rhythm of 5-6 Hz, accompanying immobilization state as well as that of 9-11 Hz, accompanying teeth chattering. The dynamics of changes of subcortical electrical activity of rats after the Locus coeruleus destruction may serve an index of the functional state of the animals under the conditions of noradrenergic deficiency. Changes of the brain electrical activity and behaviour of the animals revealed are considered to be a consequence of a relative enhancement of the central serotoninergic regulation of the subcortical structures being caused by a weakening of noradrenergic influences. PMID- 8362567 TI - [The effect of different regimens of intracellular electrostimulation on the dynamics of neuronal adaptation processes]. AB - Was studied the influence of rhythmic, random and contingent intracellular electrostimulation on the character of the initial spike activity of individual identified and nonidentified neurons of the isolated CNS of Lymnaea stagnalis snail under the conditions of the controlled experiment. Stimulation and recording of neuron activity were realized via the same microelectrode. In the process of neuron adaptation to the regimens of stimulation used two phases were distinguished being estimated with the help of various statistic criteria. The expression and stability of observed adaptive alterations of endogenous rhythm system were different during the phases determined. At the first phase which reflected a search for the strategy of the optimization of input external influences, the dispersion of interspike intervals and disorder of discharge patterns increased. The true neuron adaptation was developed at the second phase and observed only at contingent reinforcement. Such an adaptation was followed by steady alterations of endogenous rhythm system resulted in minimization or maximization of frequency of associative auto-reinforcements. Alterations accompanying the effect of optimization of external influences were the most expressive at the end of the epoch of corresponding contingent stimulation and remained for some minutes after its cessation. In the paper are discussed the possible mechanisms of the observed endo-neuronal adaptive reconstructions of spike activity. PMID- 8362568 TI - [The behavioral consequences of prenatal hemic hypoxia in rat progeny]. AB - The prenatal hemic hypoxia was caused by methemoglobin inducing agent, sodium nitrite, injected intraperitoneally in different doses from 10th to 19th day of pregnancy. It was shown that perinatal hemic hypoxia evoked delayed neurological deficit (disorders of motor coordination, hypodynamia) and disturbances of mnestic functions (impairment of learning and memory in passive and active avoidance paradigms and in the test of extrapolative water escape). The most pronounced disorders of CNS functions were shown in offsprings of male rats injected with sodium nitrite in a dose of 40 mg/kg. PMID- 8362569 TI - [The role of the right hemisphere in the invariance of the recognition of faces]. PMID- 8362570 TI - [The behavioral and neurohormonal manifestations of repeated emotional stress in intact and chronically alcoholized monkeys]. PMID- 8362571 TI - [The partial replacement of a complex stimulus by one of its components during animal learning]. PMID- 8362572 TI - Correlation of cytologic and histologic features in variants of papillary carcinoma of the thyroid. AB - Different morphologic variants have been described for papillary carcinoma of the thyroid, but little emphasis has been placed on their cytologic patterns. We studied fine needle aspiration (FNA) smears and histologic sections from 48 cases of papillary carcinoma, including 24 of the usual type, 13 of the follicular variant, 7 of the encapsulated variant and 4 of the tall cell variant, in an attempt to correlate the cytologic features and the different histologic variants. Single cells, monolayers and papillary fragments were present in all the variants. The presence of follicles was not restricted to the follicular variant. Nuclear grooves and cytoplasmic pseudoinclusions were present in most of the cases, with nuclear grooves the most common finding in all the variants (92.3 100%). Psammoma bodies were an infrequent finding (0-25%) and were absent from the follicular variant. Colloid was present in all the variants and was a frequent finding in the follicular variant (84.6%). The findings suggest that the exact histologic variant of papillary carcinoma cannot be predicted from the appearance of the fine needle aspirate. PMID- 8362573 TI - Effect of fine needle aspiration biopsy on the histology of thyroid neoplasms. AB - We evaluated the effect of fine needle aspiration biopsy (FNAB) upon the histology of thyroid adenoma and differentiated thyroid carcinoma. When surgery was performed within three months of FNAB, infarction was found histologically in 8/82 (9.8%) of the tumors. It was extensive in four patients, with one patient having no residual neoplastic cells identifiable within the nodule. No infarction was seen in the histologic specimens from patients with similar pathology whose surgery was performed without prior FNAB. These findings confirm previous reports that infarction may be caused by FNAB and can be so extensive as to interfere with the histologic diagnosis. PMID- 8362574 TI - Needle aspiration cytology of chondrosarcomas. AB - The rarity of chondrosarcomas, limited experience with the spectrum of histopathologic and cytologic features, and the drastic treatment options that ensue present a diagnostic challenge to many cytopathologists who interpret needle aspirate biopsies of these neoplasms. Twelve fine needle (FNA) aspirates were performed at University Hospitals of Cleveland on eight patients with primary (three), locally recurrent (seven) or metastatic (two) chondrosarcoma between 1980 and 1991. The cytologic features of chondrosarcoma in all three clinical settings were characterized by the presence of isolated or loosely cohesive aggregates of oval or polygonal chondrocytes with vacuolated or granular cytoplasm and a background of chondroid matrix. FNA cytology is utilized most commonly in the diagnosis of recurrent and metastatic chondrosarcoma. FNA cytology, when employed in the diagnosis of chondrosarcoma, necessitates the same considerations employed in evaluating surgical biopsies. They include (1) the cytologic features and their limitations and differential diagnoses, (2) the clinical and radiographic data, and (3) the clinical impact of the cytologic diagnosis. PMID- 8362575 TI - Processing fine needle aspiration biopsies for electron microscopic examination. Experience implementing a procedure. AB - While processing needle rinses from fine needle aspiration biopsy material for electron microscopy, we experienced difficulties not fully outlined previously. Problems in preservation were traced to the time elapsed before glutaraldehyde was added to the needle rinse, which had been held in a physiologic transport medium; a tendency toward hypotonicity of the commercially prepared transport medium; and vigorous handling of the needle rinse. When these problems were dealt with, preservation improved dramatically. The problem of scanty material available for ultrastructural evaluation was dealt with by decreasing the number of smears made and filtering the needle rinse to capture tissue fragments. Implementation of the procedure required leadership, good communication, motivated cytotechnologists and cytopathologists, and continuous supervision and monitoring. In cases with adequately cellular well-preserved material available for electron microscopy, ultrastructural evaluation made a contribution of clinical value to the diagnosis in 48% of cases. PMID- 8362576 TI - Cytologic diagnosis of pulmonary cryptococcosis in immunocompetent hosts. AB - Four immunocompetent patients with pulmonary cryptococcosis were diagnosed by either fine needle aspiration (FNA) cytology or sputum cytology over five years. The pulmonary manifestations were subpleural nodules and pneumonic infiltrates. Percutaneous transthoracic FNA under real-time ultrasound guidance for the subpleural nodules was used, as were periodic acid-Schiff stain and Liu's stain. Three of the patients with no evidence of extrapulmonary involvement received no antifungal therapy, and spontaneous resolution of the infection without recurrence was noted during follow-up. The role of cytology in the diagnosis of this unique and often-unsuspected subset of pulmonary fungal disease is emphasized. PMID- 8362577 TI - Abdominal tuberculosis. Diagnosis by fine needle aspiration cytology. AB - One hundred five cases of tuberculosis of the abdomen (excluding genitourinary involvement) diagnosed initially by fine needle aspiration cytology between 1988 and 1991 were analyzed retrospectively. The diagnosis of tuberculosis was suspected clinically in 60% of the cases prior to aspiration. The anatomic locations of the lesions were ileocecal in 69 cases, lymph node in 18, colon in 10, jejunoileal in 2, duodenojejunal in 1, peritoneal in 1 and liver in 4. Cytomorphologic analysis of the aspirates from these 105 cases showed only necrotic material in 19 cases, necrotic material with epithelioid granuloma in 36 cases and epithelioid granuloma without necrosis in 50 cases. Ziehl-Neelsen staining for acid-fast bacilli was positive in 47 of 105 cases (45%). Cultures for mycobacteria were positive in 5 of 24 cases. Histologic confirmation was available in five cases only. The cytodiagnosis correlated well with the radiologic findings and response to antituberculosis chemotherapy. PMID- 8362578 TI - Aspiration biopsy cytology of primary cutaneous tumors. AB - Primary cutaneous neoplasms may undergo fine needle aspiration during the workup of patients with suspected metastatic disease. Such aspirates present a wide range of epithelial and nonepithelial proliferations that must be separated from more common metastatic deposits. The majority of primary cutaneous tumors are composed of squamous or basaloid cells that can be confused with metastatic squamous cell carcinoma. In addition, primary cutaneous lymphomas and mesenchymal tumors morphologically overlap their more common systemic or metastatic counterparts in appearance. Both clinical and cytologic features aid in the differentiation of pilomatrixomas, basal cell carcinomas, sebaceous carcinomas, primary squamous cell carcinomas, Merkel cell tumors and epidermal inclusion cysts from metastatic squamous cell carcinomas. The presence of small basaloid cells in an aspiration smear favors the diagnosis of a primary neoplasm, such as pilomatrixoma or basal cell carcinoma. Clinical findings and cell marker studies are important in the cytologic diagnosis of primary cutaneous lymphomas. Complex convolutions in the nuclei of neoplastic lymphoid cells favor a primary cutaneous origin. We report the cytologic features of 94 primary cutaneous tumors seen in a series of 558 aspirates of subcutaneous and cutaneous nodules. PMID- 8362579 TI - Homogenization of sputum with dithiothreitol for early diagnosis of pulmonary malignancies. AB - Homogenization of sputum with dithiothreitol (DTT) has not been used in cytology for the detection of malignant cells. We examined the efficacy of this method as compared to the conventional "pick and smear" (PS) method. Smears were prepared from sputum samples using the PS technique to act as the control. The remaining sputum was digested with an equal volume of 0.3% DTT in 70% ethanol at room temperature. The cells were washed with 35% ethanol and smears prepared. The DTT treated specimens gave a much higher concentration of evenly distributed cells. The background was clear and the morphology comparable to that of the control. More positive cases were detected with the DTT than the conventional PS technique. Homogenization of sputum with DTT is a simple and effective method of screening for pulmonary malignancies. PMID- 8362580 TI - Peroral fine needle aspiration cytology of parapharyngeal lesions. AB - Peroral fine needle aspiration cytology (FNAC) was carried out on 63 patients with parapharyngeal lesions from January 1986 to March 1992. The age of the patients ranged from 4 to 87 years. Analysis of the results showed 12 inflammatory lesions, 28 benign tumors and 23 malignant neoplasms. Correlation with histopathology showed a diagnostic accuracy of 88.2%, with no false-positive reports. FNAC can replace incisional biopsy, which may be hazardous in this area. Surgery can be avoided for inflammatory lesions. PMID- 8362581 TI - Vaginal intraepithelial neoplasia. Reproducibility of pathologic diagnosis and correlation of smears and biopsies. AB - Masked slides of 124 vaginal smears and 70 corresponding biopsies obtained from 45 patients with a reported cytologic diagnosis of vaginal intraepithelial neoplasia (VAIN) were examined by two pathologists to assess the interobserver reproducibility and histopathologic correlation of cytopathologic diagnoses of VAIN. The cytopathologic diagnoses by the two pathologists were identical in 94 (76%) cases and matched the originally reported diagnosis in 45 (46%) cases. The histopathologic diagnoses by the two pathologists agreed in 47 (67%) cases and matched the originally reported diagnosis in 35 (55%). The consensus cytopathologic and histopathologic diagnoses rendered by the pathologists agreed within one grade in 49 (70%) cases. A consensus histopathologic diagnosis of VAIN 2 was rendered in only 1 (10%) of 10 cases in which the cytopathologic diagnosis was VAIN 2. These results suggest that the cytopathologic and histopathologic grading of VAIN is moderately reproducible. Because (1) combining VAIN 2 and 3 under the diagnosis of high grade squamous intraepithelial lesion provided a slight improvement in diagnostic reproducibility and cytopathologic histopathologic correlation and (2) the cytopathologic diagnosis of VAIN 2 was employed rarely and rarely confirmed histopathologically, we advocate the use of the term high grade squamous intraepithelial lesion to designate VAIN 2 and 3. PMID- 8362582 TI - Atypical glandular cells in cervical smears from women who have undergone cone biopsy. A potential diagnostic pitfall. AB - Twelve cervical smears from nine women who had cervical cone biopsies performed at least six months preceding the smears contained atypical glandular cells that raised the possibility of adenocarcinoma in situ (AIS). However, these smears differed from those usually seen in AIS in that the abnormal cells were less frequent and part of a spectrum of more benign-appearing cells, some of which appeared to be endometrial. A separate review of cervical smears following 31 consecutive cone biopsies showed that 16 of 54 contained crowded glandular cells. However, in only one case were they suggestive of AIS. Alteration of the microscopic anatomy of the endocervix following cone biopsy may be responsible for the exfoliation of such cells. PMID- 8362583 TI - Value of urine cytology in screening patients with prostatitis syndromes. AB - We reviewed the results of urine cytology examination of 206 patients with a diagnosis of prostatitis syndromes in the period 1985-1991. The urine samples showed an incidence of 20.4% for slight to moderate atypia and 6.3% for severe atypia. In these patients, cystoscopy, bladder biopsies and intravenous urography were performed to exclude malignancies. In only 6 of the 13 patients with severe atypia of the urine cytology were malignancies found. In cases of malignancy, the ages of the patients ranged from 51 to 64 years (mean, 58.6), and they complained most frequently of irritative bladder symptoms. In these patients, urinalysis frequently showed leukocyturia, and in all the samples, erythrocyturia was found. PMID- 8362584 TI - Cytologic diagnosis of cholesterol granuloma. A case report. AB - Cholesterol granuloma is a rare lesion of the orbit occurring in adults and must be distinguished from epidermoid cholesteatoma and other mass lesions of the orbit. We report the case of a 31-year-old man who presented to our institution with right eye proptosis secondary to a soft tissue mass. At surgery, cyst fluid from the lesion was sent for cytologic evaluation. The fluid was remarkable for numerous inflammatory cells, blood breakdown products, multinucleate giant cells and cholesterol crystals. The absence of squamous- or respiratory-type epithelium led to a diagnosis of cholesterol granuloma. This was confirmed by histologic examination of the tissue submitted. The differential diagnosis and cytologic features of orbital lesions are discussed. PMID- 8362585 TI - Cytodiagnosis of Coats' disease from an ocular aspirate. A case report. AB - This paper describes the cytologic findings in a rare condition, Coats' disease, which was diagnosed from a sample of ocular aspirate in a 19-month-old boy. The cytologic findings were characterized by the presence of numerous cholesterol crystals, rare foamy macrophages, several pigment-laden macrophages, pigment bearing epithelial cells and free pigment, which stained positive for melanin by Schmorl's stain. The case was unusual in that the clinical diagnosis was persistent hyperplastic primary vitreous, and other diagnoses, such as Coats' disease, were unsuspected. The cytologic findings suggested Coats' disease and seemed to exclude retinoblastoma or another malignancy, although the negative findings with the presence of cholesterol crystals and macrophages were regarded as somewhat nonspecific for unequivocally excluding any of the above. PMID- 8362586 TI - Papillary carcinoma of the male breast. Report of a case diagnosed by fine needle aspiration cytology. AB - An 81-year-old male with prostatic carcinoma presented with a large right breast mass and underwent a fine needle aspiration biopsy, which revealed a primary papillary carcinoma of the breast. This lesion was unrelated to the patient's prostatic carcinoma and is the first case of papillary carcinoma of the male breast, to our knowledge, diagnosed by fine needle aspiration cytology. This case is described, and previous literature on the cytologic features of papillary breast carcinoma and carcinoma of the male breast is briefly reviewed. PMID- 8362587 TI - Diagnosis of collagenous spherulosis of the breast by fine needle aspiration cytology. A report of two cases. AB - We describe the cytopathologic features of two cases of collagenous spherulosis of the breast on fine needle aspiration cytology. The main findings were a moderately rich cellular aspirate, monolayered epithelial clusters with bland nuclei, naked bipolar nuclei and light green (Papanicolaou stain) or pink (Diff Quik) spherules surrounded by a ring of comma-shaped nuclei resembling myoepithelial cells, located either at the heart of the epithelial clusters or detached from them. We also comment on the differential diagnosis with adenoid cystic carcinoma of the breast, signet-ring carcinoma and myospherulosis. PMID- 8362588 TI - Pericardial extramedullary hematopoiesis in a neonate with congenital heart disease. A case report. AB - A case of pericardial extramedullary hematopoiesis in a neonate with congenital heart disease was diagnosed by fine needle aspiration cytology. Undifferentiated blasts, promyelocytes, metamyelocytes and nucleated red blood cells were evident in the pericardial fluid specimen. The differential diagnosis of bone marrow contamination of pericardial fluid secondary to inadvertent sampling of neonatal hypodense bone tissue is also discussed. To our knowledge, this is the first reported case of neonatal pericardial extramedullary hematopoiesis associated with congenital heart disease. PMID- 8362589 TI - Intraoperative demonstration of Mikulicz cells in nasal scleroma. A case report. AB - The frozen section diagnosis of scleroma (rhinoscleroma) may pose some difficulty to the unsuspecting pathologist. Intraoperative cytology is a helpful technique that, when combined with frozen section, enhances the diagnostic accuracy. Imprint smears obtained from a tissue sample of an obstructive nasal mucosal mass demonstrated the characteristic Mikulicz cells, thus confirming the frozen section diagnosis of scleroma. The importance of intraoperative cytology in the evaluation of surgical specimens is emphasized. PMID- 8362591 TI - Follicular carcinoma of the thyroid with an adenoid cystic pattern. Report of a case with aspiration biopsy cytology, immunohistochemistry and electron microscopy. AB - Aspiration biopsy of a histologically confirmed follicular carcinoma of the thyroid with an adenoid cystic pattern revealed numerous epithelial cells with scant cytoplasm and oval or pleomorphic nuclei present singly, in clusters or around round, laminated bodies. PMID- 8362590 TI - Fine needle aspiration cytology of primary squamous cell carcinoma of the thymus. A case report. AB - We present the cytologic findings of a rare case of primary thymic squamous cell carcinoma with ultrastructural examination and histologic confirmation of the tumor. The clinicopathologic features of thymic carcinomas are discussed. Although the cytodiagnosis of squamous cell carcinomas in general is not difficult, we have observed some cytologic (and histologic) features that we think are distinctive in thymic squamous carcinoma. PMID- 8362592 TI - Microfilariae of Wuchereria bancrofti in a lymph node aspirate. A case report. AB - Microfilariae of Wuchereria bancrofti were detected by fine needle aspiration biopsy (FNAB) in an axillary lymph node from a 27-year-old female. The patient also had intestinal tuberculosis. A routine hemogram did not show any eosinophilia, and three consecutive night blood samples also were negative for microfilariae. This was an early case of filariasis without microfilaremia and was detected by FNAB of the lymph node. The association of filariasis and tuberculosis was purely coincidental. PMID- 8362593 TI - Ultrasonically guided fine needle aspiration of the parathyroid. A report of two cases. AB - Two cases of parathyroid adenoma were diagnosed with ultrasound-guided fine needle aspiration. Both patients were clinically suspected of having features of primary hyperparathyroidism. On aspiration, one had an associated cystic change with golden brown fluid and the other a markedly cellular aspirate. The cells aspirated were differentiated from thyroid epithelial cells. PMID- 8362594 TI - Fine needle aspiration cytology of lipid-secreting breast carcinoma. A case report. AB - Lipid-secreting carcinoma is a rare type of invasive carcinoma of the breast first described by Aboumrad et al in 1963. We believe lipid-secreting carcinoma to be a specific type of breast carcinoma and that it has to be differentiated from invasive lobular carcinoma. We report for the first time the fine needle aspiration cytologic features along with the histologic and electron microscopic findings. PMID- 8362595 TI - Intraparotid Leishmania donovani lymphadenitis: diagnosis by fine needle aspiration. PMID- 8362596 TI - Microfilaria in a thyroid aspirate smear: an unusual finding. PMID- 8362597 TI - Localized pulmonary amyloidosis diagnosed by fine needle aspiration cytology. PMID- 8362598 TI - Diagnosis of malignant melanoma of soft parts in a nodal metastasis by fine needle aspiration cytology. PMID- 8362599 TI - Megakaryocyte, erythroid and granulocyte-macrophage colony formation in myelodysplastic syndromes. AB - Bone marrow progenitor cell assays of three cell lineages, i.e., colony-forming unit megakaryocytes (CFU-Meg), burst-forming unit erythrocytes (BFU-E) and colony forming unit granulocyte-macrophages (CFU-GM), were performed for 21 patients with myelodysplastic syndromes (MDS). Markedly reduced or absent colony formation was found in 67% of the patients for CFU-Meg and all patients except 2 with refractory anemia (RA) for BFU-E. Abnormal CFU-GM colony formation was found in only 5 of 12 patients with RA and RA with ring sideroblasts, in contrast to all of the RA patients with excess of blasts and excess of blasts in transformation. Defective colony formation of all three cell lineages was seen in 63% of the MDS patients. The colony number of CFU-Meg correlated significantly with the numbers of both BFU-E and CFU-GM. These findings indicate that hematopoiesis in MDS patients is disturbed due to a qualitative or quantitative defect at the multipotent stem cell level. PMID- 8362600 TI - Hematotoxicity of interleukin-2 in man: clinical effects and comparison of various treatment regimens. AB - BACKGROUND: Immunotherapy using recombinant human interleukin-2 (rIL-2) produces objective responses in a proportion of advanced cancer patients. While early investigators employed intravenous (i.v.) treatment regimens, recent clinical trials applied therapy schedules via subcutaneous (s.c.) injection, mostly in combination with recombinant human interferon-alpha (rIFN-alpha). There were no significant differences in reported response rates between i.v. and s.c. treatment regimens. METHODS: We retrospectively evaluated 148 treatment cycles of s.c. immunotherapy administered to 107 outpatients. Adverse effects of s.c. cytokine therapy were described with regard to hematotoxicity, and compared to adverse effects reported upon high- or intermediate-dose i.v. rIL-2 therapy. Our study population consisted of 15 patients who received s.c. rIL-2 at doses of 4.8 14.4 million IU/m2/day on 5 days per week, 20 patients who were treated with rIFN alpha 2b at 3.0-6.0 million U/m2/day thrice weekly, and 72 patients who were given s.c. rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus s.c. rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week. RESULTS: Subcutaneous immunotherapy as administered in this study was well tolerated in the outpatient setting. Thus, there were no treatment related deaths, and no patient developed grade III or IV (WHO) toxicity. Subcutaneous rIL-2 as a single agent produced grade II anemia and granulocytopenia in 7% of patients, respectively. In combination with s.c. rIFN alpha, s.c. rIL-2 yielded grade II anemia and granulocytopenia in 8 and 14% of patients, respectively. In comparison, rIFN-alpha as a single agent produced grade III anemia and grade I granulocytopenia in 5 and 20% of patients, respectively. Upon s.c. rIL-2/rIFN-alpha combination therapy, a mean hemoglobin nadir of 114.4 g/l (p < 0.0001 when compared to baseline) was noted, and the mean granulocyte nadir was 2.3/nl (p < 0.0005). These mild laboratory changes due to cytokine-induced hematotoxicity were in marked contrast to severe anemia, thrombocytopenia, and granulocytopenia reported upon i.v. rIL-2 therapy. CONCLUSIONS: Palliative s.c. rIL-2-based immunotherapy as used in this study abrogates profound hematotoxicity, previously seen upon rIL-2-based i.v. immunotherapy. Subcutaneous rIL-2/rIFN-alpha combination therapy can be given in the ambulatory setting with good practicability and excellent safety. This outpatient regimen is as effective in advanced renal cell cancer as the most aggressive i.v. rIL-2-based protocols reported. PMID- 8362601 TI - Pancytopenia in children with brucellosis: clinical manifestations and bone marrow findings. AB - Among 276 paediatric cases of brucellosis seen over a 7-year period, 16 patients (5.8%) with pancytopenia were identified. The most frequent presentations were fever, malaise, anorexia, weight loss, arthralgia, and hepatosplenomegaly. Fourteen patients (87.5%) had positive blood and/or bone marrow cultures for Brucella melitensis. Bone marrow aspiration specimens showed hypercellularity in 14 patients and normocellularity in 2. Histiocytes, eosinophils and plasma cells were increased in every marrow aspirate, and haemophagocytosis was observed in 14 patients (87.5%). Non-caseating granulomas were present in the bone marrow biopsy of 11 patients (68.8%). The pancytopenia was transient, and resolved on treatment of the Brucella infection. PMID- 8362602 TI - Management of hemosiderosis complicated by coexistent anemia with recombinant human erythropoietin and phlebotomy. AB - Patients with hemosiderosis who also suffer from coexistent anemia may be unable to tolerate frequent phlebotomies needed for depletion of body iron stores. Chelation therapy, an alternative approach, may be unsuitable for some patients due to allergic reactions, poor response or intolerance of long-duration subcutaneous administration. The use of recombinant human erythropoietin in such patients could increase the hematocrit and improve exercise tolerance allowing for more frequent phlebotomies. We report the successful use of this combined approach in two such patients. PMID- 8362603 TI - Late relapse after allogeneic bone marrow transplantation for Philadelphia positive acute lymphoblastic leukaemia. AB - Late relapse of leukaemia is rare in patients with chronic myeloid leukaemia (CML) subjected to allogeneic bone marrow transplantation in chronic phase. Herein, we report a patient who presented with acute lymphoblastic leukaemia who after chemotherapy developed a picture consistent with CML in chronic phase. He then received an allograft from an HLA-identical sister and remained in complete remission for 4 years, before he eventually relapsed with features of myeloid transformation of CML. We speculate that the same population of already transformed leukaemic progenitor cells may have given rise to the original lymphoid blast cells and the myeloid blast cells that characterized the terminal relapse. PMID- 8362604 TI - Pure red cell aplasia associated with systemic lupus erythematosus: remission after a single course of intravenous immunoglobulin. AB - Pure red cell aplasia is characterized by severe anemia, with reticulocytopenia and absence of precursor cells in the bone marrow. Many modes of treatment have been described, including the use of immunosuppressive agents. Recently repeated courses of high-dose intravenous immunoglobulins have been used successfully in patients with idiopathic pure red cell aplasia. We here describe a 22-year-old woman who developed pure red cell aplasia in the course of systemic lupus erythematosus. After failure of corticosteroid therapy the patient was treated with one course of high-dose intravenous immunoglobulins with complete remission. No further therapy was required. PMID- 8362605 TI - Periodic production of antiplatelet autoantibody directed against GPIIIa in cyclic thrombocytopenia. AB - We report here a female patient with cyclic thrombocytopenia associated with antiplatelet autoantibodies. There was an inverse relationship between the level of platelet-associated IgG and platelet count. Bone marrow megakaryocytes were normal in number even during the thrombocytopenia. The binding of monoclonal antibodies (mAbs) against glycoprotein (GP) IIb/IIIa to patient platelets was significantly inhibited in the thrombocytopenic phase, while these mAbs normally bound to patient platelets obtained during the normal platelet count. Western blotting and mAb-specific immobilization of platelet antigens showed that both plasma autoantibody and the eluted IgG from the patient platelets bound to GPIIIa. These results suggest that the periodic production of antiplatelet autoantibody against GPIIIa caused cyclic destruction of platelets in this patient. PMID- 8362606 TI - Localized renal pelvic fungal ball in a patient undergoing bone marrow transplantation. PMID- 8362607 TI - Decrease in the density of IgG-Fc receptor III (CD16) on 'toxic' neutrophils. PMID- 8362608 TI - Statistical analysis of Glanzmann's thrombasthenia in Japan. PMID- 8362609 TI - Megadose methylprednisolone for myelofibrosis. PMID- 8362610 TI - Autoimmune hemolytic anemia and cutaneous T cell lymphoma: review of the literature. PMID- 8362611 TI - [V Scientific and Educational Conference of the Polish Society of Haematology and Blood Transfusion. Platelet Disorders -- New Trends in Diagnosis and Treatment. Lublin, June 4-5, 1993. Proceedings and abstracts]. PMID- 8362612 TI - [Secondary and primary thrombocythemia]. AB - Reactive thrombocytosis is an elevation of platelet count occurring in association with certain underlying diseases such as various infections, inflammatory, neoplastic and asplenic states. Essential thrombocythemia is a myeloproliferative syndrome affecting megakaryocytes, which leads to increased numbers of circulating platelets. This disorder is characterized by splenomegaly and a clinical course punctuated by hemorrhagic and/or thrombotic episodes. PMID- 8362613 TI - [Autoimmune thrombocytopenia in pregnant women]. PMID- 8362614 TI - [Clinical significance of platelet alloantibodies]. PMID- 8362615 TI - [Thrombocytopenia associated with HIV infection]. AB - Thrombocytopenia is a common complication of human immunodeficiency virus (HIV) infection. Its pathogenesis has not yet been established. An increased platelet destruction either due to the nonspecific deposition of circulating immune complexes on platelets or to the presence of specific antiplatelet antibodies as well as direct infection of megakaryocytes by HIV with a resulting decrease in platelet production have been reported as possible mechanisms. About 30-50% of patients with moderate thrombocytopenia may show spontaneous remission. Patients with either severe thrombocytopenia (platelet count < 20 x 10(9)/l) or bleeding are usually first treated with corticosteroids or azidothymidine. If improvement does not occur, further therapeutic approaches are the same as for chronic idiopathic thrombocytopenic purpura. HIV-associated thrombocytopenia has no prognostic significance with regard to AIDS risk. PMID- 8362616 TI - [Clinical aspects of autoimmune thrombocytopenic purpura]. AB - Autoimmune thrombocytopenic purpura (ATP) is a relatively common haematological problem. ATP comprises three distinct clinical entities: idiopathic acute thrombocytopenic purpura, idiopathic chronic thrombocytopenic purpura and secondary autoimmune thrombocytopenia which is associated with other autoimmune diseases. In acute ATP the majority of patients recover spontaneously within 3 months. In chronic ATP 75% of patients respond to corticosteroids and splenectomy and need no further therapy. Other forms of treatment have been evaluated for refractory patients. This is a group of particularly high risk and more aggressive forms of treatment, which can be justified, are discussed. PMID- 8362617 TI - [Laboratory diagnosis of congenital platelet function disorders]. AB - Up-dating of diagnostics of hereditary platelet disorders has been done. Due to the development of laboratory techniques some of the thrombopathies are now well characterized at the molecular level, and it can be seen that the classification of these defects has greatly progressed. However, the most frequent inherited disorders of platelet function encountered fall into the class "platelet secretion defect" and remain incompletely defined. Evidence of storage pool deficiency should be considered in all patients with an unexplained prolongation of the bleeding time, even in the absence of the classical aggregation abnormalities. PMID- 8362618 TI - [Contribution of blood platelets to hemostasis]. PMID- 8362619 TI - [Immunology of blood platelets]. AB - Platelet specific antigen systems, their molecular structure and localization in cell membrane is presented. New techniques for the detection of platelet antibodies are discussed. PMID- 8362620 TI - Comparative anatomical studies of arteriographs of the hand and foot in primates including man. AB - In this study we have tried not only to report the variations in the arteries of the hand in Hominoidea (Pongidae and Hominidae) and the frequency with which these deviations occur, but also to deal with them phylogenetically and ontogenically. The arterial system of the human hand and foot are considered to have changed from the ground plan of Old World monkeys. In this paper, the entire arterial system of the primates including man (Cercopithecidae, Pongidae and Hominidae) is discussed in a stereoscopic analysis of angiographs. In the hand, a three-dimensional angiographic analysis of the deep palmar arterial arches and their correlating arteries revealed the following features. In Cercopithecidae, 3 deep palmar arches are formed by branches of the 2nd dorsal metacarpal artery: 2 proximal arches (the catella volaris proximalis and arcus volaris profundus) and 1 distal arch (the catella volaris distalis). The palmar intermetacarpal arteries arise from the catella volaris proximalis and the palmar metacarpal arteries arise from the arcus volaris profundus. In Pongidae, the arches are formed by the perforating branches of the 1st dorsal metacarpal artery, and the catella volaris proximalis is more developed than the arcus volaris profundus. In Hominidae, the arches are formed by the perforating branches of the 1st dorsal metacarpal artery, and they consist of the arcus volaris profundus and an incomplete catella volaris distalis. This change may have been caused by the development of the thumb and its effect on finger movements. In the foot of Macaques, the saphenous artery, instead of the anterior tibial artery, reaches the dorsum of the foot and its branches supply most of the foot. The dorsal arteries are dominant as far as the metatarsal spaces of the lateral four toes. The 2nd dorsal metatarsal artery shows a tendency to be the single dominant artery and to give rise to even 4th plantar common digital artery through the catella plantaris distalis. This tendency was observed more clearly in other macaque species than the Japanese monkey. The perforating branch at the second proximal metatarsal space forms the arcus plantaris profundus, which is accompanied by the deep branch of the lateral plantar nerve. Beneath the arch, the catella plantaris proximalis is formed on the metatarsal bones among the perforating branches of dorsal metatarsal arteries. The posterior tibial artery forms the arcus plantaris superficialis, whose thin branches commonly enter the plantar common digital arteries. As described above, some similar arterial patterns in the hand and foot are ones that are secondarily acquired in man.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8362621 TI - The retroesophageal subclavian artery--a case report and review. AB - In an 80-year-old Japanese male cadaver, the right subclavian artery originated from the aortic arch distal to the origin of the left subclavian artery, i.e., it was the last branch of the aortic arch. It coursed obliquely upwards and to the right behind the esophagus and trachea heading for the superior thoracic aperture. Its area of distribution was normal. Here, we describe this rare anomaly, and discuss its morphologic types, development, incidence, common associated anomalies and clinical correlations. PMID- 8362622 TI - [Functional anatomy of the hypothalamic-hypophysial system: neuroendocrine control mechanism]. AB - The hypothalamic neuroendocrine mechanisms involved in the regulation of the anterior pituitary functions were reviewed on the basis of the findings obtained mainly in rats. The hypothalamic-hypophysial system has long been considered as a hormonary associated organ system. Recent development of immunohistochemistry and molecular biology, however, has localized the hormone-synthesizing neurons in the hypothalamus, and disclosed the synaptic junctions between them, between those neurons and non-hormonal neurons in the hypothalamus, and further, between neurons in the hypothalamus and other brain parts as well as peripheral nervous systems. Based on these findings, we have designated five functional areas in the hypothalamus: septopreoptic, suprachiasmatic, magno- and parvicellular paraventricular, and arcuate-median eminence areas. The neuronal transmitters in the synaptic junctions were classical transmitters and hormonal or nonhormonal peptides. Some mutual synaptic connections were found between different hormonal peptide-synthesizing neurons within the same area and even between those in the different areas. Although the significance of the neuronal regulation system cooperating with the hormonal events is largely still uncertain, they may serve to integrate the functions of hypothalamic hormone-synthesizing neurons as a whole in adjusting the homeostasis of the internal milieu of the living body. Intimate relations have recently been reported between immune system and endocrine system or hypothalamic neuroendocrine system. In this connection, it is clear that the hypothalamus acts not only as the center for neuroendocrine regulation but also as the center of the neuroendocrine-immune regulation of the living body. To thereby understand the living and reproductive strategies of animals, further accurate knowledge on the neuronal connections within the hypothalamus is needed. PMID- 8362623 TI - Structural changes of iliac cancellous bone in postmenopausal women: a scanning electron microscopic study. AB - The functional state of iliac cancellous bones in healthy postmenopausal women was investigated by scanning electron microscopy (SEM) using a modified organic preparation method. SEM analysis of the location, number, size and phase of the remodeling sites showed that normal iliac cancellous bone of postmenopausal women has high resorbing activity in the early stage of postmenopause in both the region near the cortico-endosteum and the midway region, while in the late stage of postmenopause there is a great difference in resorbing activity between the two regions; namely, the resorbing activity progressively decreases with age, but high resorbing activity is continuously present in the region near the cortico endosteum. Our results suggest the possibility that at the region near the cortico-endosteum the bone volume loss occurs continuously throughout all the stages of post-menopause, while at the midway region it occurs only in the early stage and not in the late stage of postmenopause. PMID- 8362624 TI - [Morphological study on edentulous mandibula]. AB - For the purpose of studying morphology of edentulous mandibula, not only the bone change of edentulous alveolar part, but the whole morphological change of edentulous mandibula was examined. Thirty-three edentulous mandibulae that have no sockets owing to the bone absorption of alveolar ridge and eighty dentulous mandibulae that possess no missing teeth except wisdom teeth were measured and compared. The authors obtained the following results concerning the morphological change of edentulous mandibula: 1. Although the body height was significantly low on account of bone absorption at the alveolar ridge, bone absorption at base of mandibula was not much observed. 2. Both condylar process height and coronoid process height were significantly low. 3. Mandibular angle of edentulous mandibular was greater. 4. In dentulous mandibula a negative correlation between mandibular angle and condylar process height, coronoid process height was found. A correlation between mandibular angle and the difference of total mandibular length and body length was observed. A great mandibular angle was found because it seems that the bone deposition was less at the inferior and posterior margin of mandibular angle part. 5. It seems that bone absorption at inferior and posterior margin of edentulous mandibular angle part was due to less bone deposition. Because a bite force decreased for missing teeth. PMID- 8362626 TI - Visual acuity: calculating appropriate averages. AB - Controversy surrounds the averaging of visual acuity scores. We examine this debate and provide a series of guidelines and worked examples to enable investigators to select an average (e.g. arithmetic mean, geometric mean, median) appropriate for their data. PMID- 8362625 TI - Computer-assisted instruction in emergency ophthalmological care. AB - The use of computer-assisted instruction in medical education has increased steadily in the last decade with the availability of personal computers. Many computer-assisted instruction programs train the user to handle various forms of disease or injury. Our intent was to provide medical students with more experience in managing ophthalmological emergencies, and we therefore designed a computerized teaching system for emergency ophthalmological care. The system makes it possible for inexperienced students to develop these skills, without jeopardizing the patient's health during training. Colour illustrations help teach the student to judge clinical signs. First, two classes of altogether 35 students used the teaching system. The students were shown to have gained significantly better knowledge of conditions which had been presented to them by the computerized teaching, than of conditions which had not been presented in this way. After having used the system, two other classes were asked about their attitudes towards this teaching modality. A majority regarded it as a valuable or very valuable addition to traditional methods of teaching. This type of instruction system may improve the quality of ophthalmic teaching without increasing teaching staff requirements. PMID- 8362627 TI - Effect of bicycle ergometer test on intraocular pressure in elderly athletes and controls. AB - To evaluate the effect of intensive physical exercise on intraocular pressure (IOP) in 66- to 85-year-old subjects IOP was measured before and after a maximal bicycle ergometer test. The non-glaucomatous subjects comprised 85 males and 36 female athletes and 16 male and 22 female controls of corresponding age drawn from a population register. IOP was measured using a non-contact tonometer. The results indicated a decrease (> or = 2 mmHg) in 34% of the subjects, no change in 57% and an increase in 9%. The decrease was more pronounced in subjects with higher pre-test values. In all four subjects with a pre-test value above 22 mmHg a reduction from 4 to 11 mmHg was observed. The change in IOP during physical loading was not significantly associated with the intensity and duration of exercise test. Three of the 5 male subjects with diagnosed glaucoma and undergoing hypotensive medication, who were analyzed separately, also showed a reduction in IOP during loading. In the pre- or post-test values there were no differences between the athletes and controls, while women tended to have higher IOP values than men. It is concluded that physical loading has predominantly a moderating effect, if any, on IOP in elderly men and women. PMID- 8362628 TI - Three-dimensional evaluation of optic disc pallor in open angle glaucoma. AB - We evaluated the extent of pallor on the walls of the optic cup three dimensionally using simultaneous stereophotographs of the optic discs of 29 normals, 29 ocular hypertensives and 28 primary open angle glaucomas. Pallor was located at the bottom of the optic cup. Pallor ascends the walls of the cup as its extent increases. Statistically significant differences in the extent of pallor in all four quadrants of the optic cup were observed, with the glaucomas having greater extents of pallor than ocular hypertensives, and the ocular hypertensives greater than the normals. The greatest percentage increase in mean pallor from normals to open angle glaucomas occurred on the nasal and inferior walls. This differential extent of pallor could be useful in characterizing ocular hypertension and chronic open angle glaucoma. PMID- 8362629 TI - The effect of hyperbaric oxygen breathing on the visual field in glaucoma. AB - Following the hypothesis that chronic ischemia is the main cause of functional deficiency in glaucoma, a double blind clinical experiment was carried out to study the effect of hyperbaric oxygenation in 51 glaucoma subjects, of which 31 were in the experimental group and 20 in the control group. In the experimental group there was a significant improvement of visual fields (p < 0.05), whereas there was no change in the subjects in the control group. Hyperbaric oxygen did not have any influence on intraocular pressure. The achieved visual field improvements remained stable for 3 months (p < 0.05), except for I3 and I4 isopters of the left eye and I4 isopter of the right eye, while they were considerably reduced after 6 months (p > 0.05). PMID- 8362630 TI - Properties of high-pass resolution perimetry targets. AB - Relationships between high-pass resolution perimetry ring targets and conventional perimetry and acuity targets were explored by optical analytical techniques and by comparative measurements in normal humans. High-pass resolution and acuity targets produced closely proportional resolution measurements, showing that the critical ring detail is the width of the bright core. High-pass resolution and conventional perimetry thresholds were not equally well correlated. From a purely optical point of view, high-pass resolution targets appeared to lose somewhat more contrast on defocusing. On the other hand, high pass resolution appears to show less variability in practical, clinical use. PMID- 8362631 TI - Two-year follow-up of intra-ocular pressure control with long duration argon laser trabeculoplasty. AB - The two-year results of intra-ocular pressure control in the first prospective study of standard (0.1 second) and long (0.2 second) duration argon laser trabeculoplasty are presented. The two groups were comparable for intra-ocular pressures and treatment scores at the start of the study. An early benefit in intra-ocular pressure reduction was found for 0.2 second trabeculoplasty in the first year, which disappeared during the second-ond year of follow-up. No reduction in medications occurred following laser trabeculoplasty. There was no difference in the frequency of further interventions (repeat trabeculoplasty or drainage surgery) between the two groups. There was a strong correlation between the intra-ocular pressures of the first and second treated eyes. No clinical benefit was demonstrated for the longer duration over standard argon laser trabeculoplasty. PMID- 8362632 TI - Treatment of concomitant eye and genital chlamydial infection with erythromycin and roxithromycin. AB - A single blind study of 10 days' randomly allocated treatment with erythromycin (1000 mg/day) and roxithromycin (300 mg/day) in 14 (group A) and 13 (group B) adults, respectively, all with culture-proven chlamydial conjunctivitis was performed. For comparison, 14 days' treatment with 1 g erythromycin daily given to 35 adults (Group C) with chlamydial conjunctivitis was also evaluated. Follow up was made approximately one month after start of therapy. Only 2 of the 37 men and 1 of the 25 women studied, all of whom had signs of conjunctivitis, had noticed concomitant symptoms of infection from the genital tract. Nasopharyngeal cultures were chlamydia-positive in 7 (50%), 7 (54%) and 20 (57%) of the patients in Group A, B and C, respectively, while for genital cultures the corresponding figures were 9 (64%), 8 (62%) and 23 (66%), respectively. The course with erythromycin in group C cured the conjunctivitis in 34 (97%) of the patients both clinically and microbiologically. Ten days' treatment with the same dose (Group A) did not eradicate chlamydiae from the eye in one, from the nasopharynx in 5 and from the genital tract in still another patient. The roxithromycin treatment (Group B) resulted in negative chlamydial cultures from the eyes in all 13 cases, while the nasopharyngeal and genital cultures were still positive in one patient each. The study showed that in spite of the eye being cured by macrolide therapy, other sites like the nasopharynx and the genital tract may still be colonized, why sampling for C. trachomatis from these sites should be made in tests for cure in chlamydial conjunctivitis cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362633 TI - Histochemical identification of hyaluronan in the rabbit anterior segment during the healing period after extracapsular lens extraction. AB - Extracapsular lens extractions were performed in rabbits. The eyes were examined at different time intervals after surgery with a histochemical method visualizing hyaluronan. There was positive staining for hyaluronan in the wound region from 2 to 90 days postoperatively. The staining was most intense and widespread between 7 and 14 days after surgery. A hyaluronan staining in the corneal stroma extended from the wound towards the central cornea 4 to 14 days postoperatively. The iris showed increased staining on the second postoperative day, but much less so at the other times studied. Cells on the posterior lens capsule were surrounded by hyaluronan from the seventh postoperative day throughout the observation time up to 90 days postoperatively. It is concluded that hyaluronan reacts during corneal wound healing. PMID- 8362634 TI - Ocular fatigue is the major symptom of dry eye. AB - A total of 524 consecutive new patients (195 male, 329 female, 43.4 +/- 20.8 y.o.) were evaluated for the presence of ocular fatigue and/or dry eye. Dry eye was diagnosed based on our criteria, which included symptoms, vital staining, break-up time (BUT) measurement, and the Schirmer test. Among all the patients, 21.2% (111/524) reported symptoms of ocular fatigue and 15.3% (80/524) were diagnosed as having dry eye with symptoms. Of the 111 patients who complained of ocular fatigue, 51.4% (57/111) had dry eye, which was significantly higher than the 15.3% for the entire group (p < 0.001). Additionally, 71.3% (57/80) of dry eye patients with symptoms complained of ocular fatigue, which was also significantly higher than the 21.2% among all patients (p < 0.001). Dry eye patients had a greater number of complaints (4.3 +/- 2.1 per patient) compared to controls (1.9 +/- 1.3 per patient) (p < 0.001). These findings suggest that there is a strong relation between ocular fatigue and dry eye. PMID- 8362635 TI - Variation of corneal thickness with age in young New Zealanders. AB - The central thickness of the left eyes of 1082 New Zealand students aged 5 to 20 years were measured using optical pachometry. No significant variation in corneal thickness was found with increasing age. The mean corneal thickness of the left eye was 540 +/- 25 microns. No significant differences in corneal thickness were found when the effects of sex or cultural groupings were examined. Corneal thickness appears to remain constant between the age of 5 and 20 years, irrespective of sex or cultural grouping. PMID- 8362636 TI - Toxic effects of ouabain on the rabbit corneal endothelium. AB - Rabbit corneas kept in a standard tissue culture medium, were continually exposed to ouabain 10(-3) M, and cultivated for 2, 3 and 4 days. The endothelium was still intact with a complete cell cover after 2 days of ouabain exposure. Total destruction of the endothelium was found in the corneas cultivated for 3 and 4 days. The corneal epithelium, however, appeared to be unaffected. Other rabbit corneas were exposed for three days to ouabain concentrations of 10(-4) M, 10(-5) M, 10(-6) M, 10(-7) M, 10(-8) M, and 0 M. The corneas exposed to 10(-4) M demonstrated total endothelial cell damage. The specimens exposed to concentrations from 10(-5) to 10(-8) M, presented dose dependent endothelial impairment as compared with the control corneas (0 M). Tracer experiments showed that the endothelial barrier was intact as long as there was a continuous cell cover, as estimated by light, transmission and scanning electron microscopy. PMID- 8362637 TI - Brown's syndrome. A longitudinal long-term study of spontaneous course. AB - The prognosis for spontaneous improvement of Brown's syndrome has not yet been clarified. The present longitudinal long-term study comprised 10 patients with idiopathic Brown's syndrome arising or noticed during the first or second year of life. They were followed for an average of 13 years during which each had a mean of 9 examinations. Spontaneous improvement occurred in 9 of the patients, 3 of whom were cured, obtaining normal motility. All three cases had initially been permanent and monolateral, with initially mild, moderate, and severe restriction, respectively. In the remaining 6 patients who changed for the better, the spontaneous improvement consisted of a reduction of the initial hypotropia and the initial depression of the adducted eye. When the patients were last seen, the sensorial state of binocular vision demonstrated in 4 of the 10 normal binocularity, in 2 binocularity corresponding to microstrabismus, and in 4 alternating suppression. PMID- 8362638 TI - Intraocular pressure after extracapsular cataract extraction with implantation of posterior chamber lenses. AB - To determine factors which influence postoperative intraocular pressure (IOP) we retrospectively reviewed changes in pressure during the first postoperative week in 633 consecutive eyes undergoing extracapsular cataract extraction (ECCE) with implantation of a posterior chamber lens. The material was restricted to four surgeons and two types of lenses. IOP was measured preoperatively, one day and one week after surgery. Glaucomatous eyes (n = 113) as well as exfoliative non glaucomatous eyes (n = 79) had a higher mean IOP (27.8 and 26.1 mmHg) the first postoperative day compared to 'simple' cataract eyes (20.1 mmHg). After one week mean IOP in glaucomatous eyes still remained elevated while exfoliative non glaucomatous eyes had regained preoperative values. Mean IOP on the first postoperative day (18.8, 24.5, 23.1 and 13.2 mmHg respectively) was also dependent on surgeon. To some extent the IOP could be correlated to tightness of suturing as estimated by keratometry. Only one surgeon had significant difference between irrigated and non-irrigated visco-elastic substance. Postoperative pressure was not only dependent on the status of the patient's eye, but factors for the individual surgeons seemed to be as important. PMID- 8362639 TI - Refractive results after phacoemulsification and ECCE. A comparative study. AB - The refractive results were evaluated in 79 patients undergoing cataract extraction by phacoemulsification using a 6-7 mm tunnel incision, and compared with a group of 77 patients undergoing planned extracapsular cataract extraction (ECCE) by the same surgeon. A mean increase in the keratometric cylinder of 0.05D and 0.52D was found in the phacoemulsification and the extracapsular cataract extraction group, respectively. This was significantly different from zero for the extracapsular cataract extraction group (p < 0.05) but not for the phacoemulsification group (p > 0.05). By vector analysis, the mean surgically induced astigmatism was 0.91D and 1.36D in the phacoemulsification and the extracapsular cataract extraction group, respectively (p < 0.01). The IOL power prediction error (spectacle plane) was found to be 0.17D (+/- 0.69 SD) in the phacoemulsification group and 0.02 D (+/- 0.79 SD) in the extracapsular cataract extraction group, respectively. We conclude that phacoemulsification improves the surgical control of the refractive outcome of cataract surgery. PMID- 8362640 TI - Autofluorescence in cataractous human lens and its relationship to light scatter. AB - The autofluorescence profile of the lens was measured from 84 eyes of 84 patients with cortical, nuclear, posterior subcapsular, or mixed lens opacities. Measurements were performed with a fluorometer in the blue-green autofluorescence range (495 nm/520 nm). The mean maximum autofluorescence value differed in every cataract group statistically significantly from that of the age matched controls (p < or = 0.0058). The highest autofluorescence values were measured in nuclear and mixed cataract groups (p < 0.0001) with high and narrow autofluorescence profile. In cortical cataracts the curve was low and flattened and the mean maximum autofluorescence value was lower than in the control eyes (p < 0.0001). The maximum autofluorescence was related to lens coloration as well as to visual acuity only in nuclear cataract. The regression between maximum autofluorescence and light scatter was statistically significant only in the nuclear cataract group (p = 0.0004). Since the autofluorescence profiles differed not only in height but also in width between the cataract groups, various width/maximum autofluorescence ratios were measured. In nuclear and mixed cataract groups the ratio 75% width/maximum autofluorescence was statistically significantly lower than in other groups (p < 0.0001). In cortical cataracts the ratio (50% width - 75% width)/maximum autofluorescence was statistically significantly higher than in other groups (p < 0.0001). PMID- 8362641 TI - Long-term effectiveness of modified grid laser photocoagulation for diffuse diabetic macular edema. AB - Fifty eyes of 42 patients with background diabetic retinopathy and diffuse macular edema were included in a prospective, randomized, clinical study to determine the long-term visual results of modified grid laser photocoagulation compared with the natural course of the disease. At the end of the three annual follow-up visits there were more eyes with improved visual acuity in the treatment group and more eyes with worse visual acuity in the control group. However, statistical analysis of the data showed that only at the end of the first and the second year was there a significant statistical difference between the two groups. At the end of the third year no statistically significant difference was found. These results suggest that modified grid laser photocoagulation is not an effective procedure for the long-term management of diffuse diabetic macular edema compared with the natural course of the disease. PMID- 8362642 TI - Natural course in fellow eyes of patients with unilateral age-related exudative maculopathy. A fluorescein angiographic 4-year follow-up of 45 patients. AB - A prospective fluorescein angiographic study of 45 patients with unilateral age related exudative maculopathy revealed at the 4-year follow-up that 14 (31%) had developed neovascular membranes in the fellow eyes. Age, drusen size and confluence, as well as pigmentary changes of these 14 were compared with the corresponding characteristics of the 31 eyes that remained non-exudative (atrophic). No significant differences were found. Among the 14 eyes that developed exudative maculopathy, visual acuity (Snellen) deteriorated 3-4 steps in 6 eyes (43%), 5-6 steps in 4 eyes (28.5%), and 7-8 steps or more in 4 eyes (28.5%). Among the 31 eyes that remained non-exudative, visual acuity was unchanged in 20 eyes (64%), deteriorated 1-2 steps in 7 eyes (23%), 3-4 steps in 3 eyes (10%), and 5-6 steps in 1 eye (3%). Social blindness (6/60 or less in the better eye) was found among 79% of the patients who had developed exudative maculopathy, whereas the figure was 19% among patients who still had atrophic macular degeneration. PMID- 8362643 TI - Maculopathy caused by welding arcs. A report of 3 cases. AB - It is well known that radiation from welding arcs can cause keratoconjunctivitis and 'glassblower's cataract'. In literature only few cases of welding arc maculopathy have been reported. Three cases are presented. PMID- 8362644 TI - Results of Crawford tube intubation in children. AB - Between 1987-1991 we inserted Crawford tubes in the nasolacrimal system in 24 children with recurrent epiphora following unsuccessful probing. Twenty-two are free of epiphora and discharge from 6 months to 4 years after the removal of tubes and 2 children show no improvement. Apart from mild epistaxis at the time of the tube insertion and tube displacement within 2 weeks of insertion in 3 children, we report no other complications. PMID- 8362645 TI - Intraocular lens prediction and oculometric harmony. With special reference to skew ratios between axial length and corneal curvature radius. AB - The oculometric features have been analysed in two groups of cataract patients, each comprising 30 subjects. All had undergone ECCE and insertion of biconvex Rayner 2 Superflex posterior chamber IOL. Using Binkhorst and SRK II routinely, the groups were given by a good fit between methods (discrepancy between emmetropia predictions numerically < 1 D) and a poor fit (actual discrepancy range 1.6-4.1 D, all with the same sign, the lower values being predicted by Binkhorst). A certain overlapping between groups was found regarding axial length and corneal curvature radius, the ranges being 21.5-25.1/22.7-29.9 mm and 7.3 8.5/7.2-8.1 mm, respectively. In contrast there was no overlapping regarding the ratio between axial length and corneal curvature radius; the ranges were 2.80 3.05 and 3.06-3.90 in the two groups. Evaluating the actual prediction errors by the two methods (follow-up after at least 4 months), they did not primarily pertain to very short or very long eyes, as usually advanced. Skew ratios between axial length and corneal curvature appeared more decisive. Possible implications for the current IOL prediction formulas, including the newer generations, are discussed. PMID- 8362646 TI - The histopathological changes of keratoconus. AB - Seven keratoconus corneas and two normal corneas were examined in a light microscope. The histopathological changes are described with emphasis on breaklines in Bowman's layer. They seem to be a late and a secondary phenomenon. The severity of the findings are compared to the loss of visual acuity. It seems that there is no fixed correlation between the histopathological findings and the loss of visual acuity. Two of the keratoconus corneas showed the same histological changes as those found in the normal corneas. PMID- 8362647 TI - Bilateral intraocular pressure elevation and decrease of facility of aqueous humour outflow as a consequence of regional lymphoedema of head and neck. AB - Aqueous humour drainage to the deep cervical lymphatics has been proven in animal experiments, but there have been no observations of changes in intraocular pressure (IOP) or aqueous humour drainage as a consequence of lymph drainage dysfunction. The history of a patient with non-Hodgkin's lymphoma, who underwent a left-sided radical neck dissection in January 1991, is reported. From the end of 1991 lymphoedema of the head and neck, predominantly on the right side, developed without venous stasis but with significant bilateral IOP elevation and aqueous humour outflow reduction, refract to conventional treatment. Two days after cytostatic treatment the lymphoedema disappeared, and IOP and aqueous humour outflow became normal. Four days later the patient died because of an acute bronchopneumonia. The pathological examination revealed an intact internal jugular venous system, enlarged lymph nodes and, as a consequence of previous irradiation, cicatrization in the right side of the neck. On the left side, there was absence of the internal jugular vein and jugular lymphatic trunk due to previous radical neck dissection. Our case suggests that regional lymphatic stasis and the absence of the collateral drainage to the contralateral side significantly reduces the aqueous humour outflow and leads to a bilateral, secondary IOP elevation. PMID- 8362648 TI - Unintentional intraocular injection of corticosteroids. AB - In this report we present a patient on whom a sub-Tenon injection of steroids was performed, with the intention of treating an active chorio-retinitis threatening the macula. The globe was inadvertently penetrated and part of the steroid solution released into the vitreous cavity. Conservative treatment was decided upon and a spontaneous complete resolution of the complication was observed after a period of 24 days. PMID- 8362649 TI - Clinicopathology of a case with retinopathy of pancreatitis. AB - Bilateral retinopathy of pancreatitis developed in a 36-year-old male patient during recurrent acute necrotizing pancreatitis. The retinopathy remained clinically unchanged between the detection and the death 6 days later. Characteristics of the retinal lesions were histologically similar to cotton-wool spots of other origin, but all the retinal vessels including vessels around and in the cotton-wool spots were intact and contained plasma and red blood cells. Absence of vascular occlusion and endothelial damage suggests that in acute pancreatitis vascular embolisation in the retina is not necessary to the development of cotton-wool patches. PMID- 8362650 TI - High prevalence of myopia among medical students? PMID- 8362651 TI - [Correlation between the structures and physicochemical properties of chemotherapeutic fluoroquinolone agents]. AB - The acid-base properties, the lipophilicity and the HPLC behaviour of nine antibacterial fluoroquinolone derivatives were studied to reveal relationship between these physico-chemical parameters and the chemical structure. Basicity of compounds with two proton-binding sites is depicted here in terms of protonation macro- and microconstants. The concentrations of microspecies (cation, zwitterion, neutral and anion) were calculated in the function of pH. The microspeciation of fluoroquinolones were used to derive relationship between the apparent and true octanol/water partition coefficients. An analysis of structure chromatographic behaviour has been performed utilizing the retention values was determined in a chromatographic system methanol-aqueous phosphate buffer/ODS. Close correlation was found between the lipophilicity and chromatographic behaviour of the tested compounds when pH dependence and the influence of an ionpairing agent were investigated. PMID- 8362652 TI - [Syntheses of potential drugs from 1-[bis(hydroxymethyl)methyl]-6,7-dialkoxy 1,2,3,4-tetrahydrois o- quinolines]. PMID- 8362653 TI - [The formulation aspects of drug liberation]. AB - Author raised problems and showed through research data some simple possibilities to achieve controlled release drug liberation. The dosage form developed during drug formulation work may influence the biological effects exerted by the active ingredients and therefore may alter the therapeutic efficacy, too. The dosage from itself includes all the chemical properties of active ingredients (salt-, ester form, polar-apolar material etc.), the physical state (crystal, amorphous, polymorphous, particle size, surface area, solvated state etc.), the value of stability and the parameters of auxiliary materials and manufacturing processes. The aim of formulation -among others-is to achieve the optimal liberation and bioavailability of drugs. The article reviews the possibilities through examples (theophylline, nitrofurantoin, phenacetin, antacids) how to make production prescriptions with high reproducibility used for the preparation of prolonged action systems with controlled release drug liberation. PMID- 8362654 TI - [Degradation of succinylcholine chloride]. AB - Quantitative thin-layer chormatographic method has been developed for the investigation of the degradation of injection formulations containing succinylcholinium chloride. The method is based on the denistometric determination of the main degradation product, choline at 430 nm after visualization with iodine vapour. The stability of the injection was investigated under various storage conditions and it has been stated that considerable decomposition takes place during as short a period as one week. PMID- 8362655 TI - [Research work in the Department of Pharmaceutical Technology of the Albert Szent Gyorgyi Medical University]. AB - A short review is given of the research carried out in recent years in the Department of Pharmaceutical Technology headed by the author on the occasion of the 75th birthday of Professor Karoly Nikolics. The main results of the scientific activities performed in the four research groups are reported and a few important references to literature are made. PMID- 8362656 TI - NMR and time-resolved optical studies of brain imaging. AB - The classical optical method of the biochemist used in so many applications to determine stoichiometry kinetics, quantitative analysis of biochemical systems which was subsequently applied to tissue studies by G.A. Millikan and others seems now to have a new lease on life provided by time and frequency resolved studies which appear to afford the essential quantification lacking in the earlier methods. The fact that localization seems possible as well may bring the optical technology into the arena of new non-invasive technology capable of high sensitivity, high resolution and rapid data acquisition. PMID- 8362657 TI - IR thermal imaging of a monkey's head: local temperature changes in response to somatosensory stimulation. PMID- 8362658 TI - Optical access to the brain: how artificial are cranial window techniques? PMID- 8362659 TI - Multiparametric imaging of microregional circulation over the brain cortex by videoreflectometry. PMID- 8362660 TI - Towards imaging of cerebral blood flow and metabolism on a microscopical scale in vivo. PMID- 8362661 TI - Towards human brain near infrared imaging: time resolved and unresolved spectroscopy during hypoxic hypoxia. PMID- 8362662 TI - Diffusion properties of brain tissue measured with electrode methods and prospects for optical analysis. PMID- 8362663 TI - Measuring oxygen using oxygen dependent quenching of phosphorescence: a status report. PMID- 8362664 TI - Infrared-interference videomicroscopy of living brain slices. PMID- 8362665 TI - Blood-brain barrier transport measurements using PET-scanning and intravenous double indicator technique. PMID- 8362666 TI - Autoradiographic and biochemical imaging in cerebral ischemia. PMID- 8362667 TI - Measurement of human hypothermic cerebral oxygen metabolism by transmission spectroscopy. PMID- 8362668 TI - Optical CT imaging of hemoglobin oxygen-saturation using dual-wavelength time gate technique. AB - Our results may be summarized as follows: 1. In-vivo hemoglobin oxygen-saturation images of rat brain can be obtained using near-infrared light. 2. The transmitted light has multiple scattered components, which degrade spatial resolution, though most of the scattering can be excluded by a suitable time-gating technique. 3. The hemoglobin oxygen-saturation of the cerebellum is higher than that of the cerebrum in untreated anesthetized rats. Although further improvements in the technique should result in better resolution, we have demonstrated the feasibility of using near-infrared light to obtain in-vivo hemoglobin oxygen saturation images. PMID- 8362669 TI - Optical properties of normal human intracranial tissues in the spectral range of 400 to 2500 nm. PMID- 8362670 TI - Optical imaging of the functional architecture in cat visual cortex: the layout of direction and orientation domains. PMID- 8362671 TI - Mapping of neural activity patterns using intrinsic optical signals: from isolated brain preparations to the intact human brain. PMID- 8362672 TI - Fiber optic imaging of subcortical neural tissue in freely behaving animals. PMID- 8362673 TI - Olfactory information processing in insects revealed by real-time optical imaging of intrinsic signals. PMID- 8362674 TI - Wavelength dependence of the differential pathlength factor and the log slope in time-resolved tissue spectroscopy. PMID- 8362675 TI - Infrared imaging of brain function. PMID- 8362677 TI - [Endoscopic correction of vesicoureteral reflux by Teflon]. AB - From March 1988, 19 vesicoureteral reflux (VUR) patients were treated by endoscopic injection of Teflon paste. Of these patients 17 cases 27 ureters were followed for more than one year. After injection of Teflon paste, reflux was eliminated in 63%, decreased in 30%, and unchanged in 7%. Then 7 ureters were injected twice and 1 ureter three times. Finally, reflux was eliminated in 93% of all cases, and decreased in 7%. Early complications were fever up in 4 cases, flank pain 3, acute cystitis 1. In the follow up period, acute cystitis occurred in 1 patient, ureter stone in 1, and renal failure in 1. However, the ureter stone and renal failure were probably not caused by this procedure. PMID- 8362676 TI - [Dietary control for out-patients in urinary stone clinic]. AB - We studied the dietary habits of 113 upper urinary tract stone formers and 24-h urine specimens before and after dietary control. Protein intake was decreased in male patients after dietary control but urinary risk factors were not changed significantly. The excretion of urinary risk factors (calcium, uric acid and oxalate) was decreased in the patients who had calcium excretion of more than 250 mg per day or uric acid excretion more than 650 mg per day or oxalate excretion more than 45 mg per day before the control. The daily protein intake was significantly correlated to urinary uric acid, calcium, and phosphate excretion and the daily vitamin C intake to urinary citrate excretion. There was a negative correlation between the daily calcium intake and urinary oxalate. The mean stone episode rate of these patients was significantly decreased from 0.174 to 0.059 stones per year by dietary control (p < 0.005). PMID- 8362678 TI - [Safety of bladder irrigation and usefulness of BLADMAN for bladder training in the patients with spinal cord injury]. AB - First, we used BLADMAN system for bladder irrigation on 47 outpatients with spinal cord injury. A syphon phenomenon of BLADMAN was applied to irrigation of the bladder. Irrigating liquid was a physiological saline solution and its volume was 500-1,000 ml. Bladder irrigation was done for 1 to 2 hours. As a result of bladder irrigation by this system, urine was clearer and the number of leucocyte in urine was decreased. There was no trouble and no side effects occurred while using this system. BLADMAN is safe and considered to be applicable to the patients with spinal cord injury. Secondly, we used BLADMAN for bladder training to the patients with spinal cord injury. Bladder training was done for 7 to 28 days on the patients with indwelling urethral catheter. The bladder function was compared before and after training. Bladder volume and compliance were significantly improved. There was no trouble while the patients used the BLADMAN system. We consider that the BLADMAN system is one of the best methods of bladder training for the patients with spinal cord injury. PMID- 8362679 TI - [Partial colpocleisis for vesicovaginal fistulas]. AB - Four patients with a vesicovaginal fistula were operated upon transvaginally using the Latzko technique of partial colpocleisis. In 3 of the 4 patients, the fistulas had been formed after total hysterectomy for myoma uteri or endometriosis. The periods from fistulization-to-surgery intervals in these 3 patients were 4 months, 12 months, and 4 years and 4 months, respectively. The fistulas in the remaining one patient had been formed after forceps delivery. The patient underwent surgery 8 days after delivery. An indwelling catheter was retained for 3 to 14 days after surgery. The 4 patients were all cured of vesicovaginal fistulas after a single operation. This paper describes our partial colpocleisis technique and discusses its clinical utility. The partial colpocleisis has the advantages of dispensing with such procedures as fistula excision, fistula opening suture, and suturation of the bladder musculature, and of closing the fistulas using a demucosated vaginal wall. Having minimal surgical invasiveness and being easy to perform and reliable, the technique appears to be excellent for coping with vesicovaginal fistulas. PMID- 8362680 TI - [Mainz pouch urinary diversion with appendix stoma]. AB - The modified Mainz pouch urinary diversion was performed on 5 patients with bladder cancer using the submucosally embedded in situ appendix as a continence mechanism. It proved to be successful on 4 patients showing the complete urinary continence without difficulty in self catheterization. One patient became incontinent and a balloon catheter was retained. Advantages of the appendix stoma in the Mainz pouch are the reduction of the ileal segment to be isolated for creation of the pouch, relative simplicity of the operative technique, and the avoidance of use of foreign bodies such as metal staples or Marlex meshes. PMID- 8362681 TI - [Clinical study of the timed voiding schedule for urinary incontinence in demented elders]. AB - Fourty-one demented elderly patients who had been diapered because of urinary incontinence in Hanwa-Senboku Hospital were treated with the one-week timed voiding schedule. Finally 14 patients (34%) became dry, and free from diapers for more than 1 week after the treatment. With regard to their cystometrogram findings, 10 (67%) of 15 patients having normoactive detrusor function, 3 (14%) of 21 patients having overactive detrusor function and 1 (20%) of 5 patients having underactive detrusor function became free from diapers after the treatment. Therefore a patient with normoactive detrusor function is thought to be a good candidate for the timed voiding schedule. Regardless of their detrusor function, those who showed good responsiveness to the treatment had better activities in daily life (better than D in the Katz index) and small amount of residual urine (less than 80 ml), indicating that not only the detrusor function but also both activities in daily life and the amount of residual urine are the important factors to reestablish voiding behavior in demented elderly patients. The timed voiding schedule is thought to be a useful method to treat incontinence in demented elderly patients, and should be tried first of all, although intermittent catheterization and/or other alternatives would be necessary for those with a large amount of residual urine with poor activities in daily life. PMID- 8362682 TI - [The characteristics of hormone responsiveness of glandular epithelium and stroma in male accessory sex organs]. AB - We investigated the hormonal responsiveness of gland and stroma in the male accessory sex organs (ventral prostate, dorsolateral prostate and seminal vesicle). Immature rats (3 weeks old) were castrated and left untreated for 4 weeks and then distributed at random into 3 groups, A, B, C. The rats in groups A, B and C were injected subcutaneously with 0.2 ml of soybean oil, 5 alpha dihydrotestosterone (DHT, 500 micrograms/day) or estradiol-17 beta (E2-17 beta, 5 micrograms/day), respectively, for 14 days before they were killed. DHT administration in prepuberal castrates stimulated collagen synthesis and accumulation in the stroma of male accessory sex organs as well as the proliferation and differentiation of the glandular epithelium in these organs. In E2-17 beta treated rats, the glandular epithelium of ventral prostate and seminal vesicle had mostly a single layer structure, but the glandular epithelium of dorsolateral prostate had a mostly multilayer structure. On the other hand, in E2 17 beta treated rats, the EMBP content, an indicator of glandular epithelium differentiation in male accessory sex organs, did not increase even in the dorsolateral prostate which showed a multilayer gland epithelium. Collagen synthesis and accumulation in the seminal vesicle was stimulated by E2-17 beta treatment several times as much as in the ventral and dorsolateral prostate. Histological investigation demonstrated that the seminal vesicle in prepuberal castrates treated with E2-17 beta resembled that of fibromuscular type human benign prostatic hyperplasia. PMID- 8362683 TI - [A case of retroperitoneal extramedullary plasmacytoma]. AB - Extramedullary plasmacytoma (EMP) is a very rare disease and mainly arises in the head and neck area. We herein reported a case of EMP arising in the retroperitoneal space. A 46-year-old man was referred to our outpatient clinic in November 1989 with the complaint of flank pain on the left side. Radiological examinations showed a tumor formation in the retroperitoneal space, which involved the left kidney, spleen and pancreas. Immunoelectrophoresis showed an elevation of serum IgG level and a spike of M-protein was detected in the serum protein electrophoresis. No bone lesions were detected, and bone marrow aspiration showed no abnormal cells. US-guided needle biopsy of the tumor led to the histological diagnosis as plasmacytoma of the IgG-kappa type. Following three cycles of preoperative chemotherapy (a THP-COP regimen), which resulted in a size reduction of the tumor by 40%, extensive resection of the tumor including extirpation of the left kidney, spleen, and tail of pancreas was performed. Because of tumor extension into the posterior wall of the stomach, however, the surgery resulted in incomplete resection. A total of 11 cycles of postoperative chemotherapy (THP-COP) was performed periodically for the residual tumor in the stomach. Rapid tumor spreading in addition to re-elevation of the serum IgG level, however, developed after the 11th postoperative chemotherapy, which extensively involved the stomach and intestines. The patient died of the disease 33 months after the initiation of treatment. PMID- 8362684 TI - [Multiple calcium oxalate stone formation in a patient with glycogen storage disease type I (von Gierke's disease) and renal tubular acidosis type I: a case report]. AB - A case of multiple urinary stones in a patient with glycogen storage disease type 1 (GSD-1) is reported. In spite of the presence of hyperuricemia, these stones did not consist of uric acid, but mainly of calcium oxalate. Laboratory studies revealed distal renal tubular acidosis and hypocitraturia, but no significant abnormality in calcium metabolism. We discussed the mechanism of calcium stone formation in our case, and its prophylactic treatment by oral administration of citrate compound. PMID- 8362685 TI - [Synchronous bilateral renal cell carcinoma in mass examination: a case report]. AB - A 65-year-old female with bilateral renal cell carcinoma which was incidentally found by general check-up developed left hemiplegia following left nephrectomy. Marked metastasis of cervical spine was demonstrated by computerized tomography scanning, which was not evident before the operation by X-ray examinations. The patient died of respiratory paralysis one month after the operation. This case was difficult to treat, because the disease advanced so rapidly. PMID- 8362686 TI - [A case of bilateral synchronous renal cell carcinoma treated with partial nephrectomy with temporary occlusion of the segmental renal artery (segmental nephrectomy)]. AB - We present a case of bilateral synchronous renal cell carcinoma. A 57-year-old man visited our hospital with a complaint of fever up. On ultrasonography and computerized tomography scan, a round tumor about 2.5 cm in diameter in the posterior portion of the right kidney and another tumor about 7 cm in diameter arising from the upper pole of the left kidney. Selective renal arteriogram showed that the inferior branch of the posterior segmental artery supplied blood to the right renal tumor. Left partial nephrectomy with temporary occlusion of the main renal artery and posterior segmental nephrectomy of the right kidney were performed at the same time. In patients with cancer confined to the posterior segment of the kidney, segmental nephrectomy can be performed while allowing unimpaired perfusion to the remainder of the kidney from the main renal artery. PMID- 8362687 TI - [Percutaneous resection of renal pelvic carcinoma: a case report]. AB - A 72-year-old male patient underwent antegrade percutaneous resection of a solitary and papillary tumor in the lower calyx of left kidney. He had undergone right nephroureterectomy one month previously due to right nonfunctioning kidney caused by right ureteral carcinoma. Percutaneous electroresection of the tumor was performed after puncture of a lower calyx. Pathological findings revealed a grade 2 transitional cell carcinoma. Second look biopsy was done on the 11th postoperative day, which showed no residual tumor pathologically. Continuous instillation of mitomycin-C 50 mg/50 ml saline with 40 cm H2O pressure for one hour was done through the nephrostomy catheter once a day, totally 7 days as an adjuvant therapy. No side effect was noticed. Cytological, radiographic studies were negative 24 months after the treatment. We discuss the indication and technical aspect of percutaneous approach to renal pelvic carcinoma. PMID- 8362688 TI - [A case of prostatic carcinoma presenting as abdominal mass]. AB - A 69-year-old man was admitted to the hospital on August 7, 1991 because of a lower abdominal mass. On physical examination, firm, rough-surfaced, unmovable masses of over fist size were palpable in the lower abdomen along with some small masses in the bilateral inguinal regions. On rectal examination the prostate was rough, hard and stony and larger than a chicken's egg in size. The serum prostatic acid phosphatase and prostatic specific antigen levels were elevated. A computerized tomography scan disclosed a large mass in the pelvis. Both a needle biopsy of the prostate and resection of an inguinal mass revealed moderately differentiated adenocarcinoma. Bone scintigram disclosed multiple metastases. Treatment with diethylstilbestrol diphosphate, etoposide, peplomycin and ifosfamide was effective, resulting in regressed intrapelvic masses and decreased serum prostatic acid phosphatase and prostatic specific antigen levels close to the normal limits. In November 1991, the patient was discharged and was surviving with the tumor as of August 1992. PMID- 8362689 TI - [A case of testicular tumor with liver metastases maintaining complete remission for a long period]. AB - A 20-year-old man was admitted with multiple lung, liver and retroperitoneal lymph node metastases from right testicular tumor. The serum hCG level was 170,000 mIu/ml. Orchiectomized right testis showed choriocarcinoma and teratoma pathologically. After 3 courses of chemotherapy of cisplatin, vinblastine and bleomycin, retroperitoneal lymph nodes were resected. Three courses of salvage chemotherapy of VP-16 (etoposide) were performed. The serum hCG level became normal and all metastases disappeared. For 37 months after operation there has been no recurrence of tumor. The 29 cases of testicular tumor with liver metastasis reported in the Japanese literatures during the last 7 years were discussed. The prognosis of testicular tumor with liver metastasis is very poor. However, adequate combination therapy might be effective for the far-advanced testicular tumor. PMID- 8362690 TI - [Pregnancy obtained by in vitro fertilization (IVF) with epididymal spermatozoa in obstructive azoospermia: report of two cases]. AB - Epididymal spermatozoa aspiration was performed in two cases of obstructive azoospermia. After the procedure, in both cases, the patient's wives obtained twin pregnancies by this method in conjunction with in vitro fertilization (IVF) and embryo transfer (ET). The patient's wife in one case had a normal delivery. The patient's wife in the other case, however, aborted artificially because she had cerebral infarction. Epididymal spermatozoa aspiration proved efficacious for male sterility in cases of obstructive azoospermia. PMID- 8362691 TI - [Clinical studies of tosufloxacin on chronic bacterial prostatitis]. AB - In a multicenter trial at 17 institutions, the usefulness of an oral dose of 300 mg of tosufloxacin (TFLX) twice a day for 14 days were assessed in the management of chronic bacterial prostatitis (CBP) diagnosed by Meares and Stamey method. Nineteen patients who were evaluated by the UTI criteria were chosen out of the 27 patients diagnosed with CBP. The isolated bacteria from EPS were 18 species and 27 strains. In terms of MICs of isolates, TFLX gave lower MICs than any of the control drugs (CPFX, NFLX, OFLX, CCL). In particular, this tendency was clear for gram-positive coccus and anaerobes. The bacteriological elimination rate obtained for 14 strains and 19 species was 89.5% (17/19) [GPC; 75.0% (6/8), GNR; 100% (7/7), Anaerobes; 100% (4/4)]. The overall clinical efficacy by the UTI criteria was documented in 94.7% (18/19). According to the doctor's evaluation, the overall clinical efficacy rate was 68.4%. Safety evaluation revealed the development of gastrointestinal symptoms in 3 cases, which were not serious, with an incidence rate of 4.0% (3/75), while no laboratory abnormalities were observed. Transference of TFLX into the prostate is slightly lower than in other new quinolones. However, from this study we considered that the higher antibacterial activity of TFLX is one of the reasons for its usefulness for CBP. PMID- 8362692 TI - Paracervical vs. intracervical block during LEEP. PMID- 8362693 TI - Anomia as a symptom of herpes simplex encephalitis. PMID- 8362694 TI - Physicians and the flu vaccine. PMID- 8362695 TI - Calcium channel blockers in the treatment of hypertension. AB - Physicians need to weigh the efficacy, adverse effects and cost of first-line antihypertensive agents. Calcium channel blockers lower blood pressure, improve coronary blood flow and depress cardiac contractility by relaxing smooth muscle and cardiac muscle. They have beneficial or neutral effects in hypertensive patients with angina, asthma, chronic obstructive pulmonary disease, postural hypotension, peripheral vascular disease, depression, sexual dysfunction, diabetes and hyperlipidemia. The major adverse effect of some calcium channel blockers is that they may worsen congestive heart failure in some patients. Because calcium channel blockers are metabolized in the liver, the dosage must be lowered in the elderly and in patients with hepatic disease. Diltiazem, verapamil and nifedipine represent prototypes of the three classes of calcium channel blockers, each with slightly different effects. PMID- 8362696 TI - Emergency management of acute coma in children. AB - A deteriorating neurologic state in a child with an acute brain insult is a life threatening situation, and the decisions made during the first few minutes of management will frequently determine the outcome. Often, the family physician is the first person contacted by the parents to evaluate the sudden change in a child. Attention must be first directed toward ensuring an airway and maintaining adequate circulation. Computed tomographic study, toxicology screen and determination of acid-base status should follow. Possible causes of acute coma in children include trauma, child abuse, intracerebral hemorrhage, tumor, meningitis and poisoning. PMID- 8362697 TI - Obtaining an exposure history. Agency for Toxic Substances and Disease Registry. United States department of Health and Human Services, Public Health Service, Atlanta, Georgia. AB - Because many environmental diseases either manifest as common medical problems or have nonspecific symptoms, an exposure history is vital for correct diagnosis. The primary care physician can--by obtaining a thorough exposure history--play an important role in detecting, treating and preventing diseases caused by toxic exposure. The exposure history consists of three parts: exposure survey, which includes information about current and past exposure, and health and safety practices at work; work history, including all past jobs and military service; and environmental history, which includes information about the home environment. PMID- 8362698 TI - High-resolution CT of the lungs. AB - High-resolution computed tomography (CT) of the lung provides detailed visualization of the lung parenchyma. The technique involves the use of thin section axial tomography. High-resolution CT can facilitate the diagnosis of certain pulmonary processes. It is useful in differentiating similar patterns of abnormalities seen on chest radiographs, such as those seen in lymphangitic carcinomatosis and sarcoidosis, and in delineating the extent of co-morbid lung diseases, such as emphysema and asbestosis. In some chronic processes such as idiopathic pulmonary fibrosis, high-resolution CT can be used for biopsy of areas of active inflammation, thus increasing the diagnostic yield. As clinicians and radiologists become more familiar with high-resolution CT, it is likely that its role in the diagnosis and assessment of lung disease will increase. PMID- 8362699 TI - NIH recommends universal screening of infants for hearing impairment. PMID- 8362700 TI - AIDS update. PMID- 8362701 TI - The birth and progress of the first heart journal. PMID- 8362702 TI - Mechanisms of angiographically successful directional coronary atherectomy: evaluation by intracoronary ultrasound and comparison with transluminal coronary angioplasty. AB - To assess the mechanisms of luminal improvement, 40 patients undergoing directional coronary atherectomy and a matched control group of 25 patients undergoing angioplasty were evaluated with intracoronary ultrasound imaging before and after intervention. Despite similar sized vessels, a similar angiographic severity of diameter stenosis (75 +/- 12% for the angioplasty group vs 69 +/- 15% for the atherectomy group, p = NS), and a similar plaque burden (percent plaque area) before intervention (84 +/- 5% in the angioplasty group vs 85 +/- 13% in the atherectomy group, p = NS), the residual plaque area after intervention was significantly smaller in the atherectomy group (54 +/- 14%) compared with the angioplasty group (65 +/- 13%, p = 0.002). Despite excellent angiographic results, significant residual plaque was noted after either successful intervention. Based on the absolute changes in lumen area, plaque area, and vessel area, improvement in the lumen area in the atherectomy group occurred as a result of plaque "compression" (48%), plaque removal (37%), and vessel expansion (15%). In the angioplasty group, plaque "compression" accounted for 94% of the improvement in lumen area, whereas vessel expansion contributed 6%. Thus "compression" of plaque remains the major mechanism of luminal improvement during atherectomy. PMID- 8362703 TI - Heterogeneity of reperfusion after reversible regional myocardial ischemia in a canine model. AB - Variability of regional myocardial blood flow (RMBF) during reflow after 20 minutes of left anterior descending (LAD) coronary occlusion was measured by the radioactive microsphere technique in nine open-chest dogs. Preocclusion RMBF in the LAD territory was 0.89 +/- 0.27 ml/min/gm. Twenty minutes of LAD occlusion resulted in uniform and severe ischemia (RMBF < or = 0.25 ml/min/gm). After 1 minute of reperfusion, RMBF in the LAD territory rose to 3.48 +/- 1.88 ml/min/gm, and declined to 1.06 +/- 0.29 ml/min/gm after 20 minutes of reperfusion. RMBF variance increased significantly from 0.046 preocclusion to 0.2857 after 1 minute of reperfusion (p < 0.01) and declining to 0.086 after 20 minutes of reperfusion. By contrast, RMBF variance analysis of myocardial segments from the nonischemic left circumflex territory exhibited no significant change throughout the experiment. In any given dog this heterogeneous reperfusion of previously ischemic tissue resulted in a disorganized topography of blood flow rates. Myocardium with relatively high regional flow was intermingled with islands of tissue with relatively low blood flow. In conclusion, despite a relatively uniform and severe myocardial ischemic insult, the subsequent initial hyperemic response during reperfusion exhibits marked spatial heterogeneity. The juxtaposition of myocardial regions exposed to vastly differing rates of oxygen delivery and washout of toxic metabolites may set the stage for nonuniform recovery of myocardial function. PMID- 8362704 TI - Sex-related differences in patients undergoing direct angioplasty for acute myocardial infarction. AB - Important sex-related differences have been recognized in several coronary artery disease presentation and treatment subsets. Little data exist describing the relative findings and outcome in women versus men who received direct percutaneous transluminal coronary angioplasty for acute myocardial infarction. We studied 670 such patients of whom 464 (69%) were men and 206 were women. The women were significantly older (67 +/- 11 years vs 61 +/- 11, p < 0.001) but had undergone less prior coronary artery bypass graft surgery (6% vs 12%, p = 0.02), whereas prior myocardial infarction (17% women vs 22% men) and coronary artery disease distribution were not significantly different. Forty-one percent of women and 43% of men had single-vessel disease (p = NS). Both women and men had 1.5 lesions/patient dilated acutely, with similar success rates (95% women, 91% men; p = 0.08). Mean ejection fractions were similar (48% in both groups), and a similar percentage in each group had an ejection fraction < 30% (10% women vs 13% men). Over a mean follow-up period of 86 weeks, the need for repeat catheterization was frequent and was similar in both groups (44% women, 47% men; p = NS), whereas documented restenosis was less common in women (20% vs 28% of patients, p < 0.05). The need for coronary artery bypass grafting was similar (15% women, 17% men; p = NS), as was the need for repeat percutaneous transluminal coronary angioplasty in the infarct vessel (14% women, 18% men; p = NS) and overall mortality (7% women, 9% men; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362705 TI - The relationship of inferior ST depression, lateral ST elevation, and left precordial ST elevation to myocardium at risk in acute anterior myocardial infarction. AB - The purpose of this study was to examine the relationship between the presence or absence of ST segment depression in inferior leads (II, III, and aVF) and ST segment elevation in lateral (I and aVL) or left precordial (V5 and V6) leads with the amount and location of myocardium at risk for infarction in patients with acute anterior myocardial infarction. Forty-three patients with anterior infarctions were injected with technetium 99m-sestamibi when they were first seen and underwent tomographic imaging to measure the amount and location of myocardium at risk. Patients with inferior ST depression (n = 10) compared with those without ST depression (n = 33) had perfusion defects that extended significantly further into the lateral wall (47 degrees vs 20 degrees, p = 0.04) and larger anterior injury vectors (6.47 vs 4.92, p = 0.008). There was no significant association with the percentage of myocardium at risk, disease of the right coronary artery, the presence of an inferior perfusion defect, or the size of the inferior injury vector. Among the patients with ST elevation in lateral leads (n = 16) compared with those without (n = 27), there was a significantly more lateral defect border (47 degrees vs 25 degrees, p = 0.007) and a larger anterior injury vector (6.07 vs 4.81, p = 0.01). There was no significant correlation with the percentage of myocardium at risk. A significant relationship could not be demonstrated between the presence of ST elevation in the left precordial leads and any measure of the amount or location of myocardium at risk. These data support the theory that inferior ST depression in patients with transmural anterior ischemia is a "reciprocal" finding and does not represent inferior ischemia. The presence of inferior ST depression or lateral ST elevation is associated with a more lateral perfusion defect. Neither of these ECG findings is associated with the amount of myocardium at risk for infarction. PMID- 8362706 TI - 99mTc-antimyosin antibody imaging for the detection of acute myocardial infarction in human beings. AB - 111In-antimyosin imaging is a highly sensitive and specific technique for the detection of myocardial necrosis. Two new methods of labeling antimyosin with 99mTc have been developed, and were compared with the standard 111In-antimyosin imaging technique in 29 patients with acute myocardial infarction. Fourteen patients (group I) received directly labeled 99mTc-antimyosin, and 15 (group II) were given RP-1 conjugated 99mTc-antimyosin. 99mTc-antimyosin imaging was performed at 6, 12, and 24 hours, and 111In-antimyosin imaging was done at 24 and 48 hours following injection. The images were interpreted by three blinded observers. In group I, 99mTc-antimyosin uptake could be detected in 3, 6, and 12 cases at 6, 12, and 24 hours, respectively, compared with only 8 cases at 24 hours with 111In-antimyosin. At 48 hours all patients showed 111In-antimyosin uptake. In group II, 99mTc-antimyosin uptake could be detected in 2, 3, and 6 cases at 6, 12, and 24 hours, respectively, compared with 8 and 12 cases at 24 and 48 hours, respectively, with 111In-antimyosin. Gated blood pool studies could be obtained in all patients following 99mTc-antimyosin injection and could be used to identify regional wall motion abnormalities. The plasma half-lives of 99mTc-antimyosin in group I and group II were 2.67 +/- 0.3 hours and 4.23 +/- 0.3 hours, respectively, and the plasma half-life of 111In-antimyosin was 6.3 +/- 0.4 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362707 TI - The effects of chronic oral milrinone therapy on early postinfarction left ventricular remodeling. AB - Left ventricular remodeling following acute transmural myocardial infarction may result in early left ventricular enlargement. To characterize the effects of milrinone on components of early left ventricular dilation, rats (n = 120) underwent left coronary artery ligation or sham surgery. In the immediate postoperative period, rats received either no treatment or milrinone (3.17 +/- 0.08 mg/kg/day) dissolved in drinking water for 20 days. Twenty-one days after the initial surgery, hemodynamic measurements were made. The rats were then put to death and the hearts arrested in diastole were excised and fixed at a constant pressure for morphometric analysis. To examine the effects of milrinone on the relative contribution of infarcted and noninfarcted segments to early left ventricular dilation after acute myocardial infarction, a subgroup of infarcted rats chosen randomly was put to death 3 days after the initial surgery for morphometric analysis. Compared with infarcted untreated rats, infarcted milrinone-treated rats had a lower left ventricular volume (1.41 +/- 0.07 ml/kg vs 2.16 +/- 0.19 ml/kg, p < 0.001), lower left ventricular wall stress (0.64 +/- 0.03 vs 0.91 +/- 0.06, p < 0.001), and a lower expansion index (1.61 +/- 0.12 vs 2.61 +/- 0.22, p < 0.001). Morphometric analysis revealed that the noninfarcted segment length did not differ between the two infarcted groups either 3 days or 21 days after left coronary artery ligation. Infarct segment length also did not differ between the two infarcted groups at 3 days, but at 21 days infarct segment was shorter in the milrinone-treated group compared with the untreated group (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362708 TI - Comparison of the natural history of irregular and smooth coronary lesions: insights into the pathogenesis, progression, and prognosis of coronary atherosclerosis. AB - The coronary arteriograms of 255 patients who had two to four arteriograms within 2.6 +/- 1.7 years were reviewed. Two hundred three patients had lesions on at least one arteriogram; among the 167 patients without coronary surgery, there were 48 complex irregular lesions (suggesting a ruptured plaque and/or thrombosis) and 141 smooth lesions with follow-up, and 73 irregular and 164 smooth lesions with preceding arteriograms available. Severe irregular lesions (> or = 90% diameter occlusion) progressed to total occlusion (46%) more often than did severe smooth lesions (11.5%) (p < 0.01). Less severe lesions usually did not progress, with no difference in incidence of progression between irregular and smooth lesions (27.8% vs 23.9%). Irregular lesions > or = 80% usually occurred as a result of progression in less severe smooth lesion or occurred in areas that were minimally diseased or appeared normal, whereas smooth lesions > or = 80% had usually not changed since the previous arteriogram. Irregular lesions very rarely became smooth. A study of lesions in 36 patients with surgery was confirmatory. We conclude that plaque rupture is a common mechanism for progression of coronary disease but is not a common pathway for the growth of smooth lesions; irregular lesions remain irregular for years. There is no relationship between the severity of smooth plaques and their likelihood to rupture. Progression of coronary disease can occur by either of two modes: (1) gradual growth of a smooth-walled plaque or (2) plaque rupture with marked progression to a severe irregular lesion. Because most smooth and most irregular lesions remain stable for years, except possibly for > or = 90% irregular lesions, there is no anatomic finding that justifies urgent revascularization. Instability is a clinical diagnosis. PMID- 8362709 TI - Angiographic suitability for catheter revascularization of total coronary occlusions in patients from a community hospital setting. AB - To assess the frequency of totally occluded coronary arteries and their angiographic suitability for catheter-based revascularization in an unselected patient population, all coronary angiograms showing > or = 50% diameter stenosis obtained from patients in a community hospital setting, were reviewed during a 1 year period. There were 112 totally occluded arteries in 101 patients (35%). Based on coronary morphologic variables previously identified as predictive of successful revascularization, 52 (46%) totally occluded arteries were judged suitable for coronary angioplasty. Totally occluded arteries with unfavorable features for coronary angioplasty were present in 29% of patients with multivessel coronary artery disease and were more commonly present in the right coronary artery. Thus totally occluded coronary arteries are found in approximately one third of patients with suspected or known coronary artery disease studied by means of coronary arteriography in a community hospital setting. Approximately one half of the total occlusions have features favoring successful coronary angioplasty. PMID- 8362710 TI - Immediate and 6-month follow-up results of coronary angioplasty for restenosis: analysis of factors predicting recurrent clinical restenosis. AB - To determine the results of coronary angioplasty for a first restenosis, the clinical, anatomic, and procedural data of 400 consecutive patients were compared with the data of 507 consecutive patients undergoing a first angioplasty. After angioplasty for restenosis, emergency redilatation had to be performed in only 0.7% of the patients versus 3.1% of the control group (p = 0.02); nevertheless, the major in-hospital event (death, myocardial infarction, emergency coronary surgery, cerebrovascular accident) rate for patients was only slightly lower (3.3% vs 4.2%, p = NS). During the 6-month follow-up period, there were no cardiac deaths and only two myocardial infarctions in the study group, but recurrent ischemia was more frequent (37% vs 31%, p = 0.05) and resulted in considerably more elective coronary surgery (16% vs 2.6%, p = 0.001). In the study group, stepwise discriminant analysis revealed four variables significantly related to the occurrence of a second restenosis: time interval between first and second angioplasty, male gender, severity of angina, and complexity of the restenotic lesions. However, their individual predictive power was low. In conclusion, compared with angioplasty for primary lesions, angioplasty for restenosis was associated with fewer periprocedural complications and, after a 6 month follow-up, serious cardiac events were almost nonexistent but recurrent ischemia was more frequent. PMID- 8362711 TI - Usefulness of exercise SPECT-thallium to detect asymptomatic restenosis in patients who had angina before coronary angioplasty. AB - The usefulness of exercise single photon emission computed tomography (SPECT) thallium for detecting asymptomatic restenosis was assessed prospectively in 62 patients with angina before angioplasty, who underwent < or = 6-month re angiography and exercise SPECT-thallium imaging. Among patients with restenosis, nine had recurrence of angina but eight did not. These two subgroups had equivalent percentages of restenosis (71 +/- 16% vs 64 +/- 16%, NS) and extent of reversible thallium defects (2.8 +/- 1.7 vs 4.1 +/- 2.6, NS), and both subgroups had poorer hemodynamic responses to exercise compared with patients without restenosis (maximal) rate-pressure product [X 100], 258 +/- 54 and 239 +/- 33 vs 302 +/- 61; p < 0.05 and p < 0.01, respectively). Exercise testing detected fewer patients with restenosis compared to exercise SPECT-thallium imaging, especially among asymptomatic patients (25% vs 100%, p < 0.005). Asymptomatic restenosis occurs frequently, induces an amount of stress ischemia equivalent to that of symptomatic restenosis, and is efficiently detected by exercise SPECT-thallium with rest-reinjection but not by exercise testing. PMID- 8362712 TI - Myocardial perfusion scintigraphy in left bundle branch block: a perspective on the issue from image analysis in a clinical context. AB - Among selected study populations, myocardial perfusion scintigraphy (MPS) in patients with left bundle branch block (LBBB) has been reported to show a low specificity for the diagnosis of coronary disease. However, the stress electrocardiogram (ECG) is nondiagnostic in this setting. To place this method in its appropriate clinical context, we evaluated MPS in all 69 consecutive patients with LBBB studied with scintigraphy for clinical reasons during a 4-year period. Among 32 patients who underwent coronary angiography for clinical indications, per patient sensitivity, 96%; per vessel sensitivity, 84%, 50%, and 100% for left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) involvement, respectively; and per vessel specificity, 95% and 68% for LCX and RCA disease, respectively, were not significantly different from those previously published for the method in patients without LBBB. Although per patient specificity, 38%, and specificity, 39%, for LAD disease were low, the predictive value of a positive test remained relatively high (83%) owing to the small number of patients selected for angiography, in part based on scintigraphic findings, with normal coronary anatomy. In addition to a possible specific pathophysiologic cause related to LBBB, apparent perfusion abnormalities in the LAD distribution may relate to generic conditions that can make scintigraphic interpretation ambiguous, often in the anterior distribution, regardless of the clinical setting. Additionally, the apparent lack of scintigraphic specificity in the LAD distribution could relate in part to a selection bias toward catheterization of patients with induced scintigraphic abnormalities, especially in the LAD distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362713 TI - Effect of antianginal agents on the relationship between rate-pressure product and myocardial oxygen uptake. AB - To evaluate the effects of antianginal agents on the correlation between rate pressure product and myocardial oxygen uptake, multistage supine leg exercise tests were performed by 21 patients with stable effort-induced angina pectoris before and after administration of antianginal drugs (a calcium channel blocker of the dihydropyridine class [10 mg of nisoldipine orally] in 11 patients and a beta-blocker [0.2 mg/kg of propranolol intravenously] in 10 patients). The rate pressure product was closely correlated with myocardial oxygen uptake before and after administration of each drug. However, the slope of the regression line of rate-pressure product (X) and myocardial oxygen uptake (Y) became significantly steeper after the calcium channel blocker administration, and the Y-intercept was significantly increased by administration of the beta-blocker. Myocardial oxygen uptake was increased after administration of the calcium channel blocker and the beta-blocker compared with control values at corresponding rate-pressure product. These observations should be considered when the rate-pressure product is used to predict myocardial oxygen uptake in patients with angina pectoris who are receiving antianginal drugs. PMID- 8362714 TI - Visual versus quantitative assessment of the severity of coronary artery stenoses: can the angiographer's eye be reeducated? AB - The percent reduction of intraluminal diameter of 102 coronary stenoses before (n = 26), immediately after (n = 24), and 6 months after (n = 52) coronary balloon angioplasty as assessed by two observers experienced in quantitative coronary angiography and by automated measurement by means of the Cardiovascular Angiographic Analysis System (CAAS) was compared. Two hundred twenty-seven still frames were selected for analysis by CAAS and displayed for assessment by each of the observers, who were unaware of CAAS results. Comparisons with CAAS measurements were made for all still frames ("per view" analyses) and for each coronary stenosis after averaging the values obtained for a given coronary segment ("per stenosis" analyses). Intraobserver variability was tested on 21 still frames from 10 stenoses, assessed 6 weeks apart by one observer. Intraobserver variability was 5% (r = 0.98); interobserver variability was 6% (r = 0.94). Per view analyses showed that observer measurements correlated well with CAAS measurements (r = 0.89 and r = 0.90); the accuracy was -0.9% and -0.7% for observers 1 and 2, and the precision was 9% and 8%, respectively; for per stenosis analyses, the accuracy was -0.5% and -0.8% (r = 0.92 and 0.94) and the precision 7% and 6%, respectively. There was no difference in the accuracy and precision of visual assessment for lesions with < 50%- or > 50%-diameter stenoses. The occurrence of restenosis was likewise detected visually with a high sensitivity and specificity compared with CAAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362715 TI - Coronary artery diameter and coronary risk factors: a study with ultrafast computed tomography. AB - Coronary artery dilation has been described as an early effect of atherosclerosis. No noninvasive technique has been available to measure coronary size. In this study coronary diameters were measured in 100 asymptomatic subjects (89 men and 11 women, mean age 40 +/- 6 years) by means of ultrafast computed tomography (UFCT), with 3 mm thick ECG gated scans. Subjects without evidence of coronary calcium were studied. The diameter of the left main (LD) and right (RD) coronary arteries were measured. Total coronary diameter, TD = LD + RD, was determined, and univariate analysis was performed with respect to total, high density lipoprotein and low-density lipoprotein cholesterol, mean blood pressure, age, body surface area, and triglycerides. Mean LD was 4.23 +/- 0.85 mm, and mean RD was 3.06 +/- 1.08 mm. TD increased with body surface area (p < 0.001). No other variable showed any significant effect on TD in this group without evidence of atherosclerosis. UFCT can be used to noninvasively measure coronary artery diameters and may be a useful technique to detect early changes of atherosclerosis in individual patients and in population studies. PMID- 8362716 TI - Medical diagnosis of type A behavior. AB - The objective of this investigation was to develop a medically oriented examination (including a search for physical signs in addition to elicitation of symptoms) for the accurate diagnosis of type A and type B behaviors. Comprising the study were 99 post-myocardial infarction patients, 15 clinically well persons in whom clinical coronary heart disease subsequently developed, and 23 healthy type B subjects. All participants were subjected to a videotaped clinical examination during which, in addition to eliciting responses to questions, 14 possible physical or psychomotor signs (many of which are newly discovered) of type A behavior were also observed. Each physical sign and symptom was given an arbitrarily weighted score (according to its observed frequency of occurrence in previously studied and authenticated type A behavior). These total scores were then statistically analyzed to obtain a critical "diagnostic score" for the presence of type A behavior. The medically oriented videotaped clinical examination detected the presence of type A behavior in 97 of 99 (98%) successively examined postinfarction patients and in 14 of 15 (93%) subjects who were clinically well at the time of their videotaped clinical examination but who subsequently had clinical coronary heart disease. Conversely type A behavior was diagnosed by videotaped clinical examination in only 1 of 23 (4%) healthy men who previously had been found to exhibit type B behavior by prior diagnostic procedures. PMID- 8362717 TI - Usefulness of serial follow-up electrophysiologic studies in predicting late outcome of radiofrequency ablation for accessory pathways and atrioventricular nodal reentrant tachycardia. AB - A total of 408 patients received radiofrequency catheter ablation for paroxysmal supraventricular tachycardia, and 326 patients underwent serial follow-up electrophysiologic studies (early and late) after initially successful radiofrequency catheter ablation of accessory pathways (group 1, 186 patients with Wolff-Parkinson-White syndrome) and slow atrioventricular (AV) nodal pathways (group 2, 140 patients with AV nodal reentrant tachycardia). Among the patients in group 1, early (4 +/- 1 days) and late (129 +/- 14 days) studies found recurrent conduction through the accessory pathways in 12 and 16 patients, respectively. During a follow-up period of 21 +/- 7 months, recurrence of accessory pathway-mediated tachyarrhythmias was noted in six patients. Of these six patients, all had tachycardia inducible in the late study but not in the early study. Among the patients in group 2, four had recurrence of AV nodal reentrant tachycardia during a follow-up of 16 +/- 6 months. Of the four patients, one had tachycardia inducible in the early (4 +/- 1 days) study and three in the late (130 +/- 12 days) study. The results demonstrated that the early study was not as sensitive as the late follow-up electrophysiologic study in predicting late outcome of radiofrequency ablation, but both the early and late studies had a high total predictive accuracy (> 90%) in groups 1 and 2. Furthermore, only 4 of the 326 patients had initial evidence of recurrent tachycardia activated by programmed electrical stimuli during follow-up studies, suggesting that follow-up electrophysiologic studies in asymptomatic patients are not warranted. PMID- 8362718 TI - New approach to the estimation of the extent of myocardial fibrosis in patients with dilated cardiomyopathy: use of signal-averaged electrocardiography. AB - To determine whether the extent of myocardial fibrosis in dilated cardiomyopathy could be estimated noninvasively, signal-averaged electrocardiograms were recorded in 32 patients with dilated cardiomyopathy, followed by left ventricular endomyocardial biopsy. The root mean square voltage for the last 40 msec (V40), the duration of the filtered QRS complex (fQRSd) and the duration of low amplitude signals < 40 microV (LAS) were obtained by signal-averaged electrocardiography. The extent of fibrosis in all biopsy samples was measured by the point-counting method. The extent of myocardial fibrosis closely correlated with fQRSd (r = 0.623, p < 0.001), LAS (r = 0.570, p < 0.001), and V40 (r = 0.355, p < 0.05). When fibrosis was classified into intercellular and interfascicular types, the extent of intercellular fibrosis more closely correlated with fQRSd (r = 0.695, p < 0.0001), LAS (r = 0.640, p < 0.0001), and V40 (r = -0.533, p < 0.005). These results suggest that signal-averaged electrocardiograms might be useful for estimation of the extent of myocardial fibrosis, especially intercellular fibrosis in patients with dilated cardiomyopathy. PMID- 8362719 TI - Spectrum and outcome of congestive heart failure in a hospitalized population. AB - There are very few contemporary studies on the frequency and cause of congestive heart failure (CHF) in a general population. In western Sweden, inhabited by 1.64 million people, a retrospective survey was performed. All hospital records of patients with CHF, ages 16 through 65 years, were examined in all hospitals in the region. During the study period 2711 patients fulfilled the criteria for CHF or cardiomyopathy. Patients were monitored for 37 +/- 28 months. The most common cause of heart failure was coronary artery disease (IHD) (40%). Other common causes were hypertension (17%), valvular disease (13%), alcohol (11%), diabetes mellitus (10%), and systemic diseases (10%). There were positive correlations between the male sex and IHD, alcohol, and dilated cardiomyopathy; the female sex was associated with systemic diseases, valvular heart disease, and diabetes. The incidence of CHF requiring hospitalization per 100,000 in the population was 1.2 to 263 men and 1.1 to 129 women, in the youngest (age 16 to 30 years) and oldest (61 to 65 years) age groups, respectively. The 5-year survival rate was 50%. Analysis of causes performed with Cox's proportional hazards model for survival showed that age, IHD, alcohol, and diabetes were independent and powerful predictors of mortality (p < 0.001). The mode of death was progressive heart failure in 54% and sudden death in 26%. We concluded that the prognosis in patients with CHF was still very poor, even among this young population. The most common cause of CHF was IHD, and the second was hypertension. PMID- 8362720 TI - Ovarian vein thrombosis. AB - We report five cases of OVT and review the literature on this disease. Among our patients OVT was not suspected clinically and was diagnosed by CT scanning or MRI. Ultrasound imaging, utilized in three cases, failed to detect OVT. Although this disease usually occurs after delivery, in two cases it was diagnosed before delivery. Of the two postpartum cases, one had a typical presentation and the other was asymptomatic. The final case was diagnosed incidentally 5 months after removal of an ovarian carcinoma. Our experience suggests that this disease may be underdiagnosed. More widespread use of CT scanning and MRI may lead to more frequent diagnosis of OVT. The role that clinically silent OVT may play in peripartum pulmonary embolism should be clarified. PMID- 8362721 TI - The cardiologist's approach to evaluation and management of the patient with essential hypertension. PMID- 8362722 TI - Evolution of echocardiographic modalities in detection of postmyocardial infarction ventricular septal defect and papillary muscle rupture: study of 62 patients. AB - Diagnostic sensitivity of various echocardiographic modalities was assessed for postinfarct ventricular septal defect (40 patients) and papillary muscle rupture (22 patients). Two-dimensional transthoracic echocardiography enabled direct visualization of ventricular septal defect in 68% and combined two-dimensional Doppler echocardiography was diagnostic in 95%. Papillary muscle rupture was directly visualized in 45%, and severe mitral regurgitation was present on Doppler color flow images in 100%. Transesophageal echocardiography was diagnostic in all nine patients (five with ventricular septal defect and four with papillary muscle rupture) in whom this modality was applied. Thus two dimensional Doppler echocardiography (transthoracic and transesophageal if necessary) is highly sensitive in detecting postinfarct ventricular septal defect and papillary muscle rupture. PMID- 8362723 TI - Biplane transesophageal pacing echocardiography compared with dipyridamole thallium-201 single-photon emission computed tomography in detecting coronary artery disease. AB - TPE is a new diagnostic technique that uses simultaneous graded transesophageal left atrial pacing and biplane transesophageal echocardiography for the detection of pacing-induced wall motion abnormalities. In a prospective study 30 patients underwent biplane TPE, dipyridamole thallium-201 single-photon emission computed tomography (SPECT), and coronary arteriography. The sensitivity (86% vs 95%, p = not significant [NS]), specificity (89% vs 56%, p = NS), positive predictive value (95% vs 73%, p = NS), and negative predictive value (83% vs 83%, p = NS) of biplane TPE and thallium-201 SPECT in identifying patients with significant coronary artery disease was similar. In the 90 vascular territories analyzed, the agreement between biplane TPE and thallium-201 SPECT for presence or absence of significant disease was 71%. Analysis of the three major vascular territories demonstrated that each imaging modality had a high sensitivity and specificity in the left anterior descending and right coronary artery segments. However, the two techniques demonstrated poorly sensitivity in the segmental distribution of the circumflex coronary artery. In conclusion, biplane TPE compared favorably with thallium-201 SPECT in terms of safety and accuracy for detecting significant coronary artery disease. Accordingly, biplane TPE may be a suitable alternative for those patients with nondiagnostic thallium-201 SPECT studies and in those with contraindications to adenosine or dipyridamole. PMID- 8362724 TI - Interventional electrophysiology--state-of-the-art 1993. AB - The field of clinical electrophysiology has broadened significantly in the last several years, spawning a new discipline known as Interventional or Therapeutic Electrophysiology. In the United States, Electrophysiology has its own training path and accreditation requirements. One of the reasons for the growth of interest in electrophysiology is the exciting introduction of nonpharmacologic methods of arrhythmia therapy, including curative radiofrequency catheter ablation and implanted devices for antitachycardia pacing/defibrillation. The arrhythmia specialist now has at his/her disposal a wide range of options for patients with symptomatic or life-threatening cardiac arrhythmias. PMID- 8362725 TI - Successful very early in-office treatment of stress test-induced myocardial infarction with anistreplase. PMID- 8362726 TI - Release of immunoreactive endothelin from the heart during percutaneous transluminal coronary angioplasty. PMID- 8362727 TI - Postinfarction left ventricular aneurysm and ventricular septal defect assessed by precordial and transesophageal echocardiography. PMID- 8362728 TI - Acute impact of percutaneous transluminal coronary angioplasty on the ischemic burden in stable and unstable angina. PMID- 8362729 TI - Mobile thrombi in atherosclerotic lesions of the thoracic aorta: the diagnostic impact of transesophageal echocardiography. PMID- 8362730 TI - Diagnosis of papillary fibroelastoma of the mitral valve complicated by non-Q wave infarction with apical thrombus: transesophageal and transthoracic echocardiographic study. PMID- 8362731 TI - Radiofrequency catheter ablation of an accessory pathway with discontinuous retrograde conduction: potential insight into mechanism of longitudinal dissociation. PMID- 8362732 TI - Radiofrequency catheter ablation of atrial flutter in a patient with postoperative congenital heart disease. PMID- 8362733 TI - Radiofrequency catheter ablation of the accessory pathway in the permanent form of junctional reciprocating tachycardia. PMID- 8362734 TI - Bradycardia-dependent manifestation of retrograde triple atrioventricular nodal pathways: possible evidence of phase-4 block in the atrioventricular node. PMID- 8362735 TI - Cerebral thromboembolization after cardioversion of atrial fibrillation in patients without transesophageal echocardiographic findings of left atrial thrombus. PMID- 8362736 TI - Usefulness of transesophageal Doppler echocardiography in the surgical drainage of a loculated purulent pericardial effusion. PMID- 8362737 TI - Purulent pericarditis caused by group B streptococcus with pericardial tamponade. PMID- 8362739 TI - Embolic chondrosarcoma: an unusual cause of pulmonary embolism. PMID- 8362738 TI - Recurrent pulmonary embolism with second-degree atrioventricular block and near syncope. PMID- 8362740 TI - Acute pulmonary edema due to pulmonary venous obstruction by left atrial dissection. PMID- 8362741 TI - Aneurysm of the atrioventricular septum between the left ventricle and right atrium without septal defect. PMID- 8362742 TI - Multiple myeloma involving the pericardium associated with cardiac tamponade and constrictive pericarditis. PMID- 8362743 TI - QT interval prolongation and cardiac arrest during antibiotic therapy with spiramycin in a newborn infant. PMID- 8362744 TI - Role of a long-short sequence for initiation of atrioventricular reentry in Wolff Parkinson-White syndrome. PMID- 8362745 TI - Penetrating atherosclerotic aortic ulcers: the role of transesophageal echocardiography in diagnosis and clinical management. PMID- 8362746 TI - Flail tricuspid valve in ruptured aneurysm of the right sinus of Valsalva. PMID- 8362747 TI - A comparison of heparin strategies after thrombolytic therapy. PMID- 8362748 TI - ST0 or ST60. PMID- 8362749 TI - The cardiac renin-angiotensin system in heart failure. AB - The success of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular morbidity and mortality rates has led to a reexamination of the role of the renin-angiotensin system in pathophysiology. Ventricular dysfunction leading to congestive cardiac failure is associated with sequential activation of the sympathetic system and increases in plasma atrial natriuretic peptide; however, increases in plasma renin and aldosterone do not occur until very late. The renin-angiotensin system is now regarded as both a circulating and tissue hormonal system. All components of the renin-angiotensin system have been detected in the heart. ACE is localized in discrete areas of the heart, including the cardiac valves, coronary vessels, atria, and myocardium. After experimental myocardial infarction in the rat, although plasma renin and aldosterone levels are not increased, ACE in the myocardium is markedly increased. Treatment with ACE inhibitors suppresses cardiac ACE and is associated with hemodynamic improvement, reversal of the neurohumoral activation, prevention of ventricular dilatation, and remodeling and reduction in mortality rates. These results suggest that the beneficial effects of ACE inhibitors in treating congestive cardiac failure, preventing ventricular remodeling, and regressing left ventricular hypertrophy may involve not only reducing preload and afterload but also suppressing the local cardiac renin-angiotensin system. PMID- 8362750 TI - Endothelial function in congestive heart failure. AB - There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide and, therefore, a defective endothelial function could be involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure. To investigate endothelial function in humans in vivo, agents such as acetylcholine, a short-acting stimulator of the release of endothelium-derived nitric oxide, has been used. Conversely, N-mono-methyl-L-arginine, a specific inhibitor of nitric oxide synthesis from L-arginine, has recently been shown to decrease blood flow during infusion into the brachial artery of healthy volunteers (control subjects) by inhibiting the basal release of nitric oxide. Consistent with experimental studies, the blood flow response to acetylcholine is blunted in patients with chronic heart failure compared with healthy age-matched volunteers. In contrast, the decrease in blood flow induced by N-mono-methyl-L-arginine appears to be exaggerated in congestive heart failure. The blood flow response to nitroglycerin or sodium nitroprusside, endothelium-independent vasodilators, is usually preserved in patients with chronic, nonedematous heart failure, indicating a normal response of the vascular smooth muscle of resistance vessels to exogenous nitric oxide. In contrast, the dilator response of the radial artery diameter to nitroglycerin and flow-dependent dilation is impaired in patients with chronic heart failure, indicating that the abnormal flow-mediated relaxation of large arteries may be caused by both endothelial and structural abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362751 TI - Systemic and regional hemodynamic effects of perindopril in experimental heart failure. AB - The effects of converting-enzyme inhibition by perindoprilat (0.5 mg/kg, intravenously, short-term administration) or perindopril (2 mg/kg, orally, long term administration once a day for 21 days) on systemic and regional hemodynamics were studied on a new rat model of heart failure, which was induced by microembolization of coronary vessels by 15 microns plastic microspheres. Cardiac output and regional blood flows were measured by microsphere technique; the tone of the venous vessels was determined as mean circulatory filling pressure in conscious, freely moving rats. Perindoprilat evoked a much more prominent increase in kidneys, adrenal glands, intestine, and skin blood flows in embolized rats than in sham-operated rats. The differences between the effects of long-term treatment with perindopril in sham-operated and embolized rats were highly significant. Mean circulatory filling pressure was decreased by short-term and long-term administration of an angiotensin-converting enzyme inhibitor. It is concluded that venous vessels could be one of the target sites for the effects of perindopril-like drugs. PMID- 8362752 TI - Intrinsic alterations of diaphragm muscle in experimental cardiomyopathy. AB - Diaphragmatic function was investigated in the cardiomyopathic Syrian hamster (CSH) from the dilated Bio 53:58 strain, after long-term therapy with the angiotensin-converting enzyme inhibitor perindopril. Twenty-two 1-month old CSHs were treated during a 5-month period by either oral gavage with perindopril (1 mg/kg/day) (n = 11) or placebo (n = 11). Control hamsters from the F1B strain received placebo (n = 7). Mechanical properties were studied in isolated diaphragm strips electrically stimulated in both twitch and tetanic conditions. Compared with F1B control hamsters, peak active tension and positive (+dP/dtmax) and negative (-dP/dtmax) peaks of isometric tension derivative were significantly depressed in placebo treated CSHs. Compared with placebo-treated CSHs, peak active tension was significantly higher in perindopril-treated CSHs in both twitch (25 +/- 4 vs 16 +/- 1 mN/mm2; p < 0.01) and tetanus modes (56 +/- 4 vs 38 +/- 2 mN/mm2; p < 0.01). Moreover, +dP/dtmax and -dP/dtmax were improved significantly in twitch (p < 0.01 and p < 0.01, respectively) and tetanus modes (p < 0.05 and p < 0.01, respectively). We conclude that, in the CSH, long-term therapy with the angiotensin-converting enzyme inhibitor perindopril helped to preserve the diaphragmatic function. PMID- 8362753 TI - Regional hemodynamic effects of perindopril in congestive heart failure. AB - The onset of heart failure is associated with complex neurohumoral, cardiac, and vascular changes. These disorders partly explain that, in this situation, regional distribution of blood flows is hardly modified with stability or increase in heart and brain flows and impairement of limb, renal, and splanchnic blood flows. Using the bidimensional Doppler technique to measure brachial blood flow and diameter and standard clearance techniques to determine renal and hepatic blood flows, we studied the effects of perindopril, a long-lasting angiotensin-converting enzyme inhibitor, on regional hemodynamics. We demonstrated that perindopril produces a very marked increase in forearm and kidney flows but a very minor increase in the hepatosplanchnic territory, resulting in a regional distribution of cardiac output that favors the renal and musculocutaneous territories. This mechanism of action might be an important contribution to clinical improvement observed with perindopril. PMID- 8362754 TI - Angiotensin-converting enzyme inhibition in congestive heart failure: benefit and perspective. AB - Therapy with angiotensin-converting enzyme (ACE) inhibitors was developed approximately 15 years ago as a novel therapeutic approach to hypertension. Although ACE inhibitor therapy was initially reserved for patients with severe hypertension, extensive clinical experience has broadened its use. These agents should now be considered as cornerstone therapy for patients with symptomatic heart failure and are of proved value in preventing the development of this syndrome. This article reviews the key studies that have documented the efficacy of ACE inhibitors in improving clinical outcome for patients with overt congestive heart failure, as well as for those with asymptomatic left ventricular dysfunction. PMID- 8362755 TI - Autocorrelation of short-term and daily average exposure levels in workplaces. AB - Based on workplace exposure data for 16 worker-chemical combinations, the degree of autocorrelation in a series of short-term time-weighted average (TWA) exposure concentrations (7.5-min, 15-min, 30-min, and 60-min TWAs) was investigated. For 7.5-min and 15-min TWAs, consecutive values generally exhibited no correlation or positive correlation, but not negative correlation. Consecutive 30-min TWAs and 60-min TWAs showed either positive correlation, negative correlations, or no correlation. Autocorrelation functions displayed various patterns that depended on the exposure time series. The mean of the autocorrelation coefficients across all worker-chemical combinations was similar to an exponential function, which signifies that the degree of autocorrelation, on average, decreased as the interval between two averaging periods increased. Autocorrelation in a series of 8-hr TWAs also was analyzed for 10 worker-chemical combinations. In general, little autocorrelation was observed. Based on this analysis, the authors discuss a sampling strategy that, on average, would minimize the degree of correlation between measurements of short-term TWAs. PMID- 8362756 TI - Inter-rater agreement in the assessment of solvent exposure at a car assembly plant. AB - This study investigated the feasibility and the reproducibility of a retrospective assessment of solvent exposure in the painting operations of a car assembly plant. Five industrial hygienists (the raters) reviewed summary documents on plant operations and solvent exposure levels, developed from plant records and interviews. The raters independently reviewed 695 department-job-year combinations compiled from 29 work histories and used semi-quantitative scores to rate solvent exposure. Inter-rater agreement was evaluated by computing the percent concordance index and the intraclass correlation coefficient (rI). There was discordance among raters, a large proportion of which pertained to low exposure levels (1-5 ppm). The computation of the rI is sensitive to the distribution of exposure levels. A low rI can be observed for a rare exposure even if the percent concordance is high. Inter-rater agreement was good for cumulative exposure scores computed for frequent exposures: coatings (rI = 0.67), aromatic hydrocarbons (rI = 0.66), and petroleum distillates (rI = 0.62). PMID- 8362757 TI - Experimental study on the fibrogenic properties of different types of alumina. AB - The fibrogenicity of seven alumina samples was tested in rats by intratracheal instillation, and in mice by intraperitoneal injection. Histopathological studies were carried out on all animals. As an indicator for inflammatory reaction, a bronchoalveolar lavage (BAL) was performed in rats. Lactate dehydrogenase activity and protein content of the supernatant as well as the free-cell population of the lungs were studied. None of the five aluminas used for primary aluminum production showed any fibrogenic potential, while the other two, a chemical grade and a laboratory produced sample, induced fibrotic lesions. A correlation between cytological and biochemical parameters studied in BAL and the fibrosis determined by histology could be established for the quartz-treated rats, but not in the alumina-treated animals. PMID- 8362758 TI - Work-related symptoms and checkstand configuration: an experimental study. AB - Supermarket checkers are known to be at risk of upper-extremity cumulative trauma disorders. Forty-two experienced checkers checked a standard "market basket" of items on an experimental checkstand. The counter height could be adjusted (high = 35.5, low = 31.5 inches), and the pre-scan queuing area length (between conveyor belt and laser scanner) could be set to "near" or "far" lengths. Each subject scanned under the high-near, high-far, low-near, and low-far conditions in random order. Seven ordinal symptom scales were used to describe comfort. Analysis showed that both counter height and queuing length had significant effects on symptoms. Furthermore, the height of the subject affected the degree and direction of the impact of the checkstand configuration differences. The study suggests that optimization of design may be experimentally evaluated, that modification of postural as well as frequency loading may be beneficial, and that adjustability for the individual may be advisable. PMID- 8362759 TI - Effect of tool shape and work location on perceived exertion for work on horizontal surfaces. AB - Thirty subjects drove screws into perforated sheet metal mounted on a horizontal surface using three air-powered tools that varied in shape (right-angle, in-line, and pistol-shaped). The four horizontal work locations ranged from 13-88 cm in front of the body and were placed at 25 cm intervals. The vertical placement of the horizontal beam was at midthigh, elbow, and midchest height. Subjects drove 25 screws at each tool/work location combination before rating that condition using the Borg 10-point ratio rating scale. The ratings of perceived exertion increased with increasing horizontal distance from the body. When tool shape was not considered, the perceived exertion was virtually equal for driving screws at midthigh or elbow height. The ratings at midchest height were significantly higher than elbow and midthigh height. When tool shape was taken into account, subjects perceived less exertion driving screws with the pistol-shaped tool at midthigh height. The in-line and right-angle tools had the lowest ratings of perceived exertion for driving screws at elbow and midchest height. PMID- 8362760 TI - Lead exposures during shipboard chipping and grinding paint-removal operations. AB - Shipboard chipping and grinding paint-removal operations were evaluated to determine personnel exposures to airborne lead concentrations. Lead concentrations found in the bulk lead-paint samples ranged from 0.0037 to 11.5% by weight. Of the personnel conducting paint removal operations, 62% were exposed at or above the Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit for lead of 50 micrograms/m3. Correlations of airborne lead concentrations and bulk lead-paint contents for chipping and grinding operations were statistically significant. Blood lead (Pb) levels were significantly higher in the follow-up blood tests when compared to the initial blood tests taken prior to paint removal. However, blood Pb levels were well below the OSHA allowable level of 40 micrograms/100 g. PMID- 8362761 TI - Physiological evaluation of liquid-barrier, vapor-permeable protective clothing ensembles for work in hot environments. AB - Work clothes using fabrics with vapor-transmitting characteristics are in limited use in various industrial applications, and there is a growing interest in their purported ability to help reduce heat stress. This study was performed to compare two vapor-transmitting ensembles with other clothing ensembles previously tested. The evaluation was based on an established experimental protocol that determines the critical values of air temperature and water-vapor pressure so that an individual maintains thermal balance, while controlling other factors that contribute to worker heat stress (e.g., air motion and metabolism). There were no differences between the two vapor-transmitting garments in their effects on worker heat stress. When compared to the results of other studies, the two vapor transmitting garments had critical environmental characteristics similar to two layers of cotton coveralls and they performed better from a heat stress standpoint than a disposable vapor-barrier suit worn over cloth coveralls. PMID- 8362762 TI - Outcome after acute myocardial infarction in patients with prior coronary artery bypass surgery. AB - Little is known concerning the influence of remote prior coronary artery bypass grafting (CABG) on the outcome of patients with acute myocardial infarction (AMI). Therefore, this study evaluated 2,494 patients with AMI of whom 219 (8.8%) had a history of CABG a mean of 7.1 +/- 3.7 years before the index AMI. Compared with all other patients, those with a history of CABG had an increased prevalence of a history of prior AMI (153 [70%] vs 547 [24%]), congestive heart failure (48 [22%] vs 236 [10%]), and angina pectoris (165 [75%] vs 787 [35%]), all p < 0.001. There was no difference in age, but patients with prior CABG were more often men (192 [88%] vs 1,702 [75%], p < 0.001). During the hospitalization for AMI, patients with prior CABG had more recurrent ischemic pain (100 [46%] vs 732 [32%, p < 0.001]), and more frequently developed non-Q-wave AMI (72 [33%] vs 514 [23%], p < 0.01). In-hospital mortality did not differ among patients with or without prior CABG (15 [7%] vs 195 [9%]). At hospital discharge, more patients with prior CABG had complex ventricular ectopic activity on 24-hour ambulatory electrocardiographic monitoring (48 of 74 [65%] vs 327 of 797 [41%], p < 0.0001), and radionuclide ejection fraction < 0.45 (53 of 99 [54%] vs 430 of 1,024 [42%], p < 0.01). Among patients undergoing coronary angiography during the first 2 months, multivessel coronary artery disease was more prevalent among patients with prior CABG (78 of 107 [73%] vs 508 of 959 [53%], p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362763 TI - Angiographic predictors of a rise in serum creatine kinase (distal embolization) after balloon angioplasty of saphenous vein coronary artery bypass grafts. AB - Distal coronary embolization is thought to be increased in the balloon angioplasty of coronary by-pass vein grafts. One hundred fifty-five procedures of balloon angioplasty involving single vein graft dilatation were successfully performed. Distal coronary embolization was defined as an elevation of creatine phosphokinase greater than twice the preangioplasty value and positive MB fraction. Twenty procedures were found to have embolism by this definition. Forty preangioplasty angiograms were randomly selected from the remaining procedures and analyzed as a control group. Eight angiographic features were evaluated as possible risk factors for distal coronary embolization, i.e., diffusely diseased vein graft, presence of thrombus, ulcerated lesion surface, marked eccentricity, large plaque volume, lesion angulation, abrupt proximal face and ectasia. A diffusely diseased vein graft (p = 0.002), presence of thrombus (p = 0.006), irregular or ulcerated lesion surface (p = 0.007), large plaque volume (p = 0.02) and marked eccentricity (p = 0.03) were found to be important predictors by univariate analysis. A diffusely diseased vein graft and a large plaque volume were found to be important independent predictors by multivariate analysis. The presence of thrombus and an irregular or ulcerated lesion surface frequently coexist with a diffusely diseased vein graft. It is concluded that a diffusely diseased vein graft and a large plaque volume are important independent predictors of distal embolization, and thrombus and an ulcerated lesion surface are also important. PMID- 8362764 TI - Open, noncontrolled dose-finding study with a novel recombinant plasminogen activator (BM 06.022) given as a double bolus in patients with acute myocardial infarction. AB - The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mutant of tissue-type plasminogen activator expressed in escherichia coli which can be given as a bolus because of a prolonged half-life. The primary objective of this trial was to determine the efficacy of an intravenous r-PA double bolus (first bolus of 10 MU followed by 5 MU after 30 minutes) in patients with acute myocardial infarction. All patients received heparin intravenously and acetylsalicylic acid orally. Efficacy was assessed from infarct artery patency by coronary angiography (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3) in 50 patients. Ninety minutes after administration of the first r PA bolus, the infarct-related coronary artery was patent in 39 of 50 patients (78%; 95% confidence interval 64 to 88%). An angiographically confirmed reocclusion occurred in 1 patient between 90 minutes and 24 to 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic parameters showed a decrease in fibrinogen to 37% of baseline value. There were 3 clinical reinfarctions before discharge and 2 major puncture site hemorrhages. No further serious bleeding and no serious adverse event with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regimen appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limited number of patients treated in this study, one need not be concerned about the safety profile of r-PA. PMID- 8362765 TI - Effects of thrombolysis and atenolol or metoprolol on the signal-averaged electrocardiogram after acute myocardial infarction. Late Potentials Italian Study (LAPIS). AB - Late potentials (LPs) detected on the signal-averaged (SA) electrocardiogram (ECG) predict arrhythmic events after acute myocardial infarction (AMI). The effect of thrombolysis on the incidence of LPs after AMI is controversial and its impact on subsequent arrhythmic events is not known. Moreover, the effects of beta blockers on the SAECG have not been studied. Six hundred eighteen patients with AMI were studied; thrombolysis was given to 228 (37%). In comparison with patients treated conventionally, those receiving thrombolysis were significantly younger and more frequently male, had higher peak values of creatine kinase, a lower prevalence of non-Q-wave AMI, and a higher incidence of ventricular fibrillation in the acute phase, and more frequently received beta blockers. An SAECG obtained 6 to 8 days after AMI showed LPs in 24% of patients receiving and in 25% not receiving thrombolysis (p = NS). On admission, intravenous beta blockers were administered to 110 patients (18%); those receiving beta blockers were younger, had lower peak values of creatine kinase and more frequently received thrombolysis. LPs were less frequently found in patients treated than in those not treated with beta blockers (15 vs 27%; p = 0.007); however, this effect was found only in those with an ejection fraction > or = 40%. Independent predictors of LPs by multivariate analysis were an ejection fraction < 40% (p = 0.007), ventricular fibrillation in the acute phase (p = 0.02), and absence of beta-blocking therapy (p = 0.03). During a mean follow-up of 12 +/- 7 months, there were 39 cardiac deaths (6%), 13 of which were sudden (2%), and 9 sustained ventricular tachycardias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362766 TI - Usefulness of continuous ST monitoring in inferior wall acute myocardial infarction for describing the relation between precordial ST depression and inferior ST elevation. AB - To explore the relation between precordial and inferior ST-segment changes within individual patients, continuous 12-lead electrocardiographic recording was performed in 19 patients with acute inferior infarction given intravenous thrombolytic therapy. Monitoring was performed for 519 +/- 269 minutes. The extent of inferior ST elevation varied considerably with time in all patients. With use of the maximal precordial ST depression recorded to classify patients, 11 had precordial ST depression (sigma V1-3) > 0.2 mV (group A) and 8 had < or = 0.2 mV or no precordial ST depression (group B). The maximal recorded precordial ST depression correlated inversely with the corresponding inferior ST elevation in the 19 patients (r = -0.78, p < 0.001). Within individual patients, continuous 12-lead monitoring revealed a close negative correlation between the inferior and precordial ST levels for the entire recording period in many patients, but 5 of the 19 patients (26%) (2 in group A and 3 in group B) did not have this relation. Moreover, precordial ST depression was not always present during inferior ST elevation in group A patients: 4 of 11 (36%) had some electrocardiographs showing < 0.1 mV precordial ST depression despite summed inferior ST elevation > 0.6 mV. These data indicate that precordial ST depression is not just the simple electrical reciprocal projection of the abnormal inferior wall ST vector, and its fluctuation cannot be predicted by changes in inferior ST level in every patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362767 TI - Alteration in regulation of myocardial blood flow in one-vessel coronary artery disease determined by positron emission tomography. AB - The behavior of myocardial blood flow (MBF) regulation in territories supplied by angiographically normal vessels of patients with coronary artery disease (CAD) has been poorly investigated. Resting MBF and coronary reserve were evaluated in 32 patients with stable angina, no previous myocardial infarction, and isolated left anterior descending or left circumflex coronary artery stenosis (> or = 50% diameter narrowing). MBF was measured, in the absence of any medical therapy, by means of dynamic positron emission tomography and 13N-ammonia. MBF measurements at baseline and after intravenous dipyridamole (0.56 mg/kg administered over 4 minutes), were obtained both in the stenosis-related regions and in contralateral territories. As a control group, 14 normal subjects were evaluated according to the same protocol. At rest, the 32 patients with CAD had similar MBF values in the stenotic and remote regions (0.76 +/- 0.21 and 0.77 +/- 0.19 ml/min/g, respectively, p = NS); both these values were significantly (p < 0.01) reduced with respect to mean MBF in normal subjects (1.03 +/- 0.25 ml/min/g). The dipyridamole study was completed in 30 patients; these patients had lower values of maximal MBF in the stenotic than in the remote regions (1.52 +/- 0.65 vs 1.76 +/- 0.68 ml/min/g, p < 0.05); however, both these values were significantly reduced (p < 0.01) with respect to mean dipyridamole MBF in normal subjects (3.66 +/- 0.92 ml/min/g). Thus, in patients with CAD, resting and maximal MBF can be reduced not only in myocardial territories supplied by stenotic arteries, but also in territories supplied by angiographically normal arteries. PMID- 8362768 TI - Relation between clinical presentation and angiographic findings in unstable angina pectoris, and comparison with that in stable angina. AB - The diagnosis of unstable angina encompasses a broad spectrum of patients with myocardial ischemia, varying widely in cause, prognosis and responsiveness to therapy. A new clinical classification of unstable angina is based on the following 2 components: severity, and the clinical setting in which unstable angina develops. The hypothesis that this clinical classification correlates with the underlying coronary artery anatomy was tested. In 238 consecutive patients, an unstable angina score ranging from 2 to 6 was determined by adding the scores for severity (1 = unstable angina without pain at rest; 2 = pain at rest > 48 hours before angiography; and 3 = pain at rest < or = 48 hours before angiographic evaluation) and the clinical setting of unstable angina (1 = unstable angina secondary to a noncardiac condition; 2 = primary unstable angina; and 3 = early postinfarction unstable angina). Fifty concurrently studied consecutive patients with stable angina were assigned a score of 0. Patients with unstable angina averaged 63 +/- 11 years of age, and 165 were men (69%). Pain at rest occurred in 202 of 238 patients (85%), and angiography was performed < or = 48 hours in 139 of these patients (69%). Among patients with unstable angina, 5 (2%) had secondary unstable angina, 143 (60%) had primary unstable angina, and 90 (38%) had postinfarction unstable angina. Multivariable regression analysis identified the unstable angina score as the most important predictor of intracoronary thrombus (p = 0.011) and lesion complexity (p = 0.004) in the ischemia-related artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362769 TI - Relation of cardiovascular responses to mental stress and cardiac vagal activity in coronary artery disease. AB - Forty-six patients with documented coronary artery disease were studied to examine the relation of cardiovascular reactivity to mental stress and cardiac vagal activity. Cardiac vagal activity was measured by means of frequency-domain analysis of heart rate variability with 48-hour out-of-hospital Holter monitoring. The amplitude of the high-frequency component (0.16 to 0.40 Hz) of heart rate variability is considered to be an index of cardiac vagal activity. Cardiovascular reactivity was measured in the laboratory during a 3-minute public speaking task. Results revealed that (1) the amplitude of the high-frequency component was significantly higher during sleep (24.6 +/- 11.3 ms) than during waking (18.2 +/- 8.0 ms) (p = 0.002); (2) compared to subjects with low diastolic blood pressure reactivity, those who displayed high diastolic blood pressure reactivity exhibited a significantly lower amplitude of the high-frequency component (19.2 +/- 6.9 vs 23.4 +/- 9.6 ms, p = 0.03). These results indicate that decreased cardiac vagal activity may contribute to the exaggerated diastolic blood pressure reactivity to mental stress in patients with coronary artery disease. PMID- 8362770 TI - Comparative evaluation of bicycle and dobutamine stress echocardiography with perfusion scintigraphy and bicycle electrocardiogram for identification of coronary artery disease. AB - In 66 patients with suspected coronary artery disease (CAD), exercise electrocardiography (ECG), exercise echocardiography, dobutamine stress echocardiography (dosage, 5 to 40 micrograms/kg/min), single-photon emission computed tomography (SPECT) using methoxy-isobutyl-isonitrile (MIBI) and coronary angiography were performed prospectively to compare methods for detecting CAD. CAD was defined as 70% luminal area stenosis in at least 1 coronary artery at coronary angiography. Significant CAD was present in 50 patients. Compared with exercise ECG, exercise echocardiography, dobutamine stress echocardiography and MIBI-SPECT had a significantly higher sensitivity (52% vs 80, 79 and 89%; p < 0.01, p < 0.01 and p < 0.001, respectively). There were no significant differences in sensitivity between exercise echocardiography, dobutamine stress echocardiography and MIBI-SPECT. Specificity of MIBI-SPECT was lowest (71%), whereas exercise ECG, exercise and dobutamine echocardiography had higher specificities (93, 87 and 81%, respectively). Significance, however, was not achieved. Differences in overall accuracy between exercise echocardiography (82%), dobutamine stress echocardiography (80%) and MIBI-SPECT (85%) were not significant. Comparison with accuracy of exercise ECG (62%) was significant (p < 0.05, p < 0.05 and p < 0.01, respectively). In 1-vessel disease, exercise ECG had a lower sensitivity (45%) than exercise and dobutamine echocardiography and MIBI SPECT (79, 78 and 84%; p < 0.02, p < 0.02 and p < 0.01, respectively). Regarding the 24 patients with false-negative exercise ECG results, 67% had positive exercise echocardiography findings, 71% positive dobutamine echocardiography results and 84% positive technetium-99m MIBI-SPECT results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362771 TI - Time course of hemodynamic changes and improvement of exercise tolerance after cardioversion of chronic atrial fibrillation unassociated with cardiac valve disease. AB - This study prospectively assessed the time course, magnitude and mechanism of the hemodynamic changes after restoration of sinus rhythm in patients with chronic atrial fibrillation (AF) unassociated with valvular disease. Severe cardiac dysfunction may occur after chronic supraventricular tachycardia in patients with and without underlying cardiac disease. Improvement may follow abolishment of the arrhythmia or adequate slowing of the ventricular rate. Eight patients were studied with a mean previous duration of AF of 10 +/- 9 months. Ejection fraction, exercise capacity and the atrial contribution to the left ventricular filling (only during sinus rhythm) were studied before cardioversion, after cardioversion and 1 week, 1 month and 6 months thereafter. A significant improvement in ejection fraction from 36 +/- 13 to 53 +/- 8% (p < 0.05) occurred at 1 month after cardioversion. Concomitantly, peak oxygen consumption had increased at 1 month, from 20.1 +/- 7 to 25.2 +/- 6 ml/min/kg (p < 0.05). Thereafter, no further improvement in hemodynamic parameters occurred. The atrial systole improved already at 1 week (from 3 +/- 5 to 16 +/- 11%, p < 0.05) and remained unchanged thereafter. Thus, restoration of sinus rhythm was associated with a delayed improvement in ejection fraction and maximal exercise capacity, preceded by an early restoration of atrial contractility and an acute slowing of the heart rate. The discrepancy in time course of restoration of atrial and ventricular function parameters suggests that an intrinsic left ventricular cardiomyopathy is present in patients with AF. PMID- 8362772 TI - Effectiveness and costs of digoxin treatment for atrial fibrillation and flutter. AB - Clinical outcomes and costs associated with the use of digoxin in atrial fibrillation and flutter were evaluated in a prospective, observational study at 18 academic medical centers in the United States. Data were collected on 115 patients (aged > 18 years) with atrial fibrillation or flutter who were treated with digoxin for rapid ventricular rate (> or = 120 beats/min). The median time to ventricular rate control (i.e., resting ventricular rate < 100 beats/min, decrease in ventricular rate of > 20%, or sinus rhythm) was 11.6 hours from the first dose of digoxin for all evaluable patients (n = 105) and 9.5 hours for those only receiving digoxin (n = 64). Before ventricular rate control, the mean +/- SD dose of digoxin administered was 0.80 +/- 0.74 mg, and a mean of 1.4 +/- 1.8 serum digoxin concentrations were ordered per patient. Concomitant beta blocker or calcium antagonist therapy was instituted in 47 patients (41%); in 19 of these, combination therapy was initiated within 2 hours. Adenosine was administered to 13 patients (11%). Patients spent a median of 4 days (range 1 to 25) in the hospital; 28% spent time in a coronary/intensive care unit and 79% in a telemetry bed. Loss of control (i.e., resting ventricular rate returned to > 120 beats/min) occurred at least once in 50% of patients and was associated with a longer hospital stay (p < 0.05). Based on 1991 data, the estimated mean hospital bed cost for patients with atrial fibrillation or flutter was $3,169 +/- $3,174.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362773 TI - Disparate cardiovascular response to stress tests during isradipine and fosinopril therapy. AB - Optimal antihypertensive therapy should control blood pressure at rest and during stress while preserving the physiologic hemodynamic response. In patients with mild to moderate hypertension, the hemodynamic profile and catecholamine response at rest, during isometric, mental, and orthostatic stresses were compared before and 12 weeks after angiotensin-converting enzyme inhibition or calcium channel blockade. Antihypertensive therapy was titrated either with the angiotensin converting enzyme inhibitor fosinopril (10 to 40 mg; n = 9) or with the calcium antagonist isradipine (5 to 20 mg; n = 10) until diastolic blood pressure < 90 mm Hg was achieved. Groups were comparable in race, sex, body mass index, pretreatment mean arterial pressure and response to isometric stress (25% increase in mean arterial pressure) before treatment. At rest, total peripheral resistance was reduced to the same extent (18%) in both groups. After fosinopril, the percent increase in stroke volume was higher and heart rate lower than with isradipine. During isometric stress, the percent increase in mean arterial pressure and cardiac output was higher, with isradipine (p < 0.05) reaching pretreatment levels. Plasma catecholamines were also higher with isradipine (p < 0.05), increasing by 100% with plasma norepinephrine compared with 16% before treatment. During orthostatic stress significant reductions in mean arterial pressure and stroke volume were observed after isradipine but not after fosinopril. Neither medication significantly modified the response to mental stress. Our data suggest that despite a comparable reduction in total peripheral resistance at rest, fosinopril preserves a more physiologic hemodynamic response to isometric and orthostatic stress than isradipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362774 TI - Comparison of clinical findings in idiopathic dilated cardiomyopathy in women versus men. The Italian Multicenter Cardiomyopathy Study Group (SPIC) AB - Clinical and laboratory findings were compared in 65 women and 238 men with invasively documented idiopathic dilated cardiomyopathy. Women had more severe symptoms (New York Heart Association class > or = III in 48 vs 39%; p < 0.05), presented more frequently with heart failure signs (63 vs 41%; p < 0.01), and had a higher cardiothoracic ratio (0.56 +/- 0.06 vs 0.53 +/- 0.06; p < 0.05) and higher frequency of left bundle branch block (41 vs 29%; p < 0.05). Echocardiographic measurements in women showed significantly greater left ventricular (LV) end-diastolic (42 +/- 7 vs 39 +/- 6 mm/m2; p < 0.0001) and end systolic (36 +/- 7 vs 33 +/- 6 mm/m2; p < 0.001) diameters, and mean myocardial thickness (11 +/- 2 vs 10 +/- 2 mm; p < 0.05). Exercise duration was shorter in women than in men (7 +/- 3 vs 10 +/- 4 minutes; p < 0.001). After 18 +/- 16 months, 9 women and 27 men died, and 7 and 17, respectively, received transplants. Transplant-free survival was not significantly different according to gender. By Cox multivariate analysis, LV ejection fraction was a significant independent predictor of cardiac death or heart transplantation in both sexes (p < 0.05 in men, and p < 0.005 in women), together with left atrial diameter index (p < 0.01) in women, and mean pulmonary artery pressure (p < 0.001) in men. In conclusion, women with idiopathic dilated cardiomyopathy present a more advanced phase of the disease with greater LV dilation, but do not have a different prognosis. PMID- 8362775 TI - Ventriculo-coronary arterial connections in pulmonary atresia with intact ventricular septum, and their influences on ventricular performance and clinical course. AB - To define the influence of ventriculo-coronary (VC) arterial connections on ventricular performance and late outcome, and associated wall motion abnormalities in patients with pulmonary atresia and intact ventricular septum, 21 patients aged > or = 6 months (mean 4.3 +/- 3.3 years, range 0.5 to 11.8) were reviewed. Ventricular volumes, mass, systolic functional variables and regional wall motion were measured using biplane ventricular cineangiography. Fourteen patients had VC connections, 11 of whom had coronary artery abnormalities. In comparing patients with VC connections and coronary abnormalities (group I) with those without coronary abnormalities (group II), no hemodynamic differences were observed, except the expected increased right-to-left ventricular systolic pressure ratio in group I (1.33 +/- 0.24 vs 0.72 +/- 0.50). Wall motion abnormalities were observed in 8 patients (7 in group I, and only 1 in group II [p < 0.05]). Ejection fraction in patients with abnormal wall motion was significantly lower (50 +/- 6% vs 57 +/- 7%; p < 0.05) and ventricular systolic pressure ratio significantly higher (1.46 +/- 0.16 vs 0.80 +/- 0.45; p < 0.05) than in those with normal wall motion. Five patients died during follow-up, all of whom had wall motion abnormalities. The findings suggest that patients with VC connections and coronary abnormalities have a higher incidence of wall motion abnormalities, which may reflect ongoing ischemia, and are at risk for late death. PMID- 8362776 TI - Transcatheter occlusion of patent ductus arteriosus in adults. AB - This study examines whether transcatheter closure of a patent ductus arteriosus (PDA) using a Rashkind PDA occluder device is safe and effective in adults, or if adults have complications not sited in children owing to prolonged aorticopulmonary communication, high surgical risks or calcified PDAs. Fifteen patients aged 22 to 76 years (mean 42 +/- 14) were referred for transcatheter PDA occlusion. Exercise intolerance was the most frequent clinical manifestation. Eleven of 15 patients had surgical risk factors that included left ventricular failure (n = 10), biventricular failure (n = 1), elevated pulmonary pressures (n = 1), and a calcified PDA (n = 5). Twelve millimeter devices were placed in 4 PDAs < or = 3 mm in diameter; 17 mm devices were placed in 11 PDAs 3 to 6 mm in diameter. Seven (47%) were occluded angiographically shortly after device placement; another 5 PDAs (33%) were occluded echocardiographically within 24 hours of the procedure. Completed occlusion in this time interval was more likely to occur in PDAs < 5 mm in diameter (p = 0.0009). Of the 3 remaining PDAs with follow-up ranging from 9 to 38 months, 2 have demonstrated gradual diminution of shunting and have trivial leaks by color/Doppler flow. The other patient with a residual PDA has no ductal flow after placement of a second device. No complications related to device implantation or closure of the PDA occurred in any patient. No complications were reported in the follow-up patients who received evaluation (14 of 15 patients; range 1 to 38 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362777 TI - Implication of aneurysmal transformation in isolated perimembranous ventricular septal defect. AB - Defects on the membranous ventricular septum (perimembranous ventricular septal defect [VSD]) may spontaneously close or diminish in size by "aneurysmal transformation" (i.e., adherence of the tricuspid valve or adjacent tissue onto the VSD). It was recently shown that the appearance of aneurysmal transformation may be associated with subaortic ridges, as well as left ventricular (LV)-to right atrial (RA) shunts. In all, 877 consecutive patients with isolated perimembranous VSD were retrospectively studied. Results of actuarial analysis showed that patients with a perimembranous VSD had a 98% probability of aneurysmal transformation by the age of 240 months. Of these patients, the expected probabilities of developing LV-RA shunt, spontaneous closure and subaortic ridge were 45, 35 and 6%, respectively. Patients with LV-RA shunts had higher probabilities of developing infective endocarditis (p = 0.002) and persistent left-to-right shunts (p < 0.001). The presence of a subaortic ridge may be accompanied by LV outflow tract obstruction (10 of 25 patients), infundibular pulmonary stenosis (n = 3), or aortic valve deformity or aortic regurgitation (n = 5), and none of those with a subaortic ridge closed spontaneously. It was confirmed that a substantial proportion of aneurysmal transformation of isolated perimembranous VSD is associated with LV-RA shunts and subaortic ridges. PMID- 8362778 TI - Predictive value of dobutamine echocardiography just before noncardiac vascular surgery. AB - This study prospectively evaluated 75 consecutive patients (mean age 69 +/- 9 years) undergoing major vascular surgery to test the hypothesis that dobutamine stress echocardiography can be used to predict perioperative cardiac events. A positive test was defined as a new or worsening wall motion abnormality in at least 2 of 18 wall segments. Up to 40 micrograms/kg/min of dobutamine was administered. All readings were done by physicians unaware of the patients' symptoms and electrocardiographic response. In addition, physicians caring for the patients were unaware of the test result. End points of the study were unstable angina with documented electrocardiographic changes, nonfatal myocardial infarction or cardiac death. The perioperative ischemic event rate was 7% (5 of 75 patients). Three patients developed unstable angina and 2 sustained nonfatal myocardial infarctions. All of these patients had positive results on dobutamine stress echocardiography (sensitivity 100%). However, 22 patients who also had positive results on dobutamine stress echocardiography did not have perioperative events (specificity 69%). The corresponding positive predictive value was 19%. None of the 48 patients who had negative results on dobutamine stress echocardiography had events (negative predictive value 100%). In conclusion, dobutamine stress echocardiography can be used to predict perioperative events with great sensitivity, but its positive predictive value in this patient population in low, likely due to the low incidence of perioperative events in patients with known coronary artery disease and the imperfect specificity of dobutamine stress echocardiography in identifying significant coronary stenosis. Dobutamine stress echocardiography is most useful in this setting when negative, because it predicts safety from complications with confidence. PMID- 8362779 TI - Rate-dependent hemodynamic responses during incremental atrial pacing in chronic constrictive pericarditis before and after surgery. AB - Chronic constrictive pericarditis is a frequent cause of diastolic dysfunction, and results in impaired ventricular filling. Unlike in normal subjects, ventricular filling in constrictive pericarditis occurs almost entirely in the initial one third of diastole, and cardiac output is dependent predominantly on heart rate. Tachycardia impairs ventricular filling in normal subjects, but its effects in patients with constrictive pericarditis have not been studied. The effect of increasing heart rate alone with atrial pacing on the central and peripheral hemodynamics of patients with untreated chronic constrictive pericarditis before and after pericardiectomy was evaluated. Increased heart rate with atrial pacing increased cardiac output, whereas stroke volume remained unchanged up to heart rates of 140 beats/min. Further increases in heart rate resulted in reductions of cardiac output and stroke volume. There were no significant changes in ventricular filling pressures. Infusion of 300 ml of saline solution at peak pacing rates did not improve cardiac output. After successful surgical pericardiectomy, the hemodynamic effects of atrial pacing returned to normal. It is concluded that moderate tachycardia improves the hemodynamic profile of patients with constrictive pericarditis. PMID- 8362780 TI - Accuracy and reproducibility of left ventricular mass measurement by subcostal M mode echocardiography in hypertensive patients and professional bicyclists. AB - In some patients, left ventricular (LV) mass cannot be evaluated by M-mode echocardiography because the parasternal long-axis view is not available. The aim of this study was to determine whether the subcostal view obtained by M-mode echocardiography under 2-dimensional guidance allows accurate and reproducible LV mass determination. Using the cube formula, LV mass was calculated, from parasternal and subcostal views in 96 subjects: 73 hypertensives and 23 professional bicyclists, covering a wide range of LV dimensions. M-mode tracings were read by 2 experienced echocardiographers and the interobserver variability was evaluated. With use of the subcostal view, the interobserver reproducibility, expressed as observer 1-observer 2, was excellent: -0.3 +/- 1.3 mm for LV diastolic diameter, -0.1 +/- 1.0 mm for ventricular diastolic septal thickness, 0.2 +/- 0.6 mm for diastolic free wall thickness and 0.03 +/- 16.7 g for LV mass. In 96% of cases, the difference in LV mass between the 2 observers did not exceed 30 g. With use of the parasternal and subcostal approaches, LV mass was not statistically different (202.6 +/- 2.2 g and 206.5 +/- 2.0 g, respectively) and the difference was < 52 g (clinically significant threshold) in 91 of 96 cases. It is concluded that, using the cube formula, LV mass calculation based on the subcostal view was accurate and not statistically different from that provided by the usual parasternal approach. PMID- 8362781 TI - The best hospitals in the USA for patients with heart disease. PMID- 8362782 TI - An inappropriate article. PMID- 8362783 TI - A growth control approach to Class II, Division 1 cases during puberty involving the simultaneous application of maxillary growth restriction and mandibular forward induction. AB - A simple method that used headgear and a functional appliance simultaneously was used for the correction of Class II, Division 1 cases with severe denture base discrepancy. The treatment restricted the forward growth of the maxilla and advanced the mandible. The functional appliance, referred to as the mandibular growth advancer (MGA), advances the mandible progressively with a splint, with the objective of remodeling the condyle and the glenoid fossa in the temporomandibular joint. Functional adaptation was achieved as the muscles that are attached to the mandible adjusted to new positions. In the two cases that illustrate this method, the ANB angle decreased and the Ar-B distance increased over a short period to four and six times the mean Japanese growth rate, respectively. After the correction of the denture-base discrepancy, a multibracket fixed appliance was used for dental alignment, and good skeletal, occlusal relationships and profiles were obtained. Treatment of severe denture base discrepancy in this manner may reduce the skeletal abnormality, decrease the number of extraction cases, and shorten the subsequent multibracket treatment time. And it may reduce the iatrogenic side effects caused by prolonged mechanotherapy with a fixed appliance. PMID- 8362784 TI - Mandibular condyle position: comparison of articulator mountings and magnetic resonance imaging. AB - This study evaluated the reliability of jaw positions, the existence of distinct jaw positions, and condyle-disk-fossa relationships in a symptom-free population by using articulator mountings and magnetic resonance imaging (MRI). The subjects examined included 28 men, 22 to 35 years of age, all having Angle Class I molar relationships and no discernible TMJ dysfunction. Records taken included the following: an axiographic face-bow to locate retruded hinge axis position, an interocclusal registration of retruded position (RE), a series of interocclusal registrations for centric occlusion (CO), a leaf gauge-generated centric relation (CR), a series of interocclusal registrations for CR, and MRI. The mandibular position indicator of the SAM articulator (Great Lakes Orthodontics, Ltd., Tonawanda, N.Y.) was used to determine reliability and existence of distinct jaw positions. Magnetic resonance imaging also evaluated jaw positions and anatomic relationships. The results indicate: (1) The articulator analysis of CO and CR is statistically replicable. (2) A distinct jaw position could be demonstrated for CO that was separate from RE and CR. It was not possible to discriminate between RE and CR. (3) Condylar concentricity was observed in half of the sample and remained consistent in RE, CO, and CR. (4) Of the sample 13% demonstrated anteriorly displaced disks that were not influenced by posterior condyle placement. (5) The clinical concept of treating to CR as a preventive measure to improve disk-to-condyle relationships was not supported by this study. PMID- 8362785 TI - Bimaxillary protrusion in black Americans--an esthetic evaluation and the treatment considerations. AB - This study attempted to discover what black Americans find attractive about their profile. Fifteen black patients (eight males, seven females) were selected at random and used as models. Lateral photographs were taken on each patient, and a computer was used to alter the profiles to depict different levels of bimaxillary protrusion. Each patient was manipulated into four different profile types according to specific numerical guidelines. A vertical reference line from soft tissue glabella, perpendicular to Frankfort horizontal, was used to measure the lip position. In each profile type only the horizontal lip position was altered. The four profile types were classified as S (straight) BM1, (bimax one), BM2 (bimax two) and BM3 (bimax three). The S profile was considered a straight or white facial profile, and the BM3 was an extreme example of bimaxillary protrusion. The photographs were surveyed among black and white laypersons, general dentists, and orthodontists. The results found the BM1 profile to be the most attractive. This was consistent with all groups surveyed. The BM1 profile would be considered a slightly convex profile and is more protrusive than white orthodontic norms. In this study comparisons of this profile to other standards are made and treatment considerations for black patients are discussed. PMID- 8362786 TI - Comparison of bond strength between lingual and buccal surfaces on young premolars. AB - The purpose of this experiment was to compare the bond strength and the failure interfaces on lingual and buccal surfaces of young human premolars. Premolar buccal brackets were adapted and bonded on the lingual or buccal surfaces of crowns after etching with a 37% phosphoric acid solution for 15 seconds. The bond strengths were 7.2 MPa and 7.0 MPa for lingual and buccal surfaces, respectively. The bond failure interfaces were located between the bracket and the resin, within the resin itself, or between the resin and the enamel. Tooth fragmentation was not found. There were no statistically significant differences (p > 0.05). This indicates that it is not necessary to specially treat a lingual surface for increasing the bond strength. PMID- 8362787 TI - The influence of bracket design on moment production during axial rotation. AB - The interaction between the bracket of an axially rotated tooth and arch wire produces a moment. This moment influences tooth movement and rotational control and is itself influenced by bracket width and bracket ligation. Self-ligating spring clip brackets fasten to and interact with arch wires differently than conventionally ligated brackets. An in vitro study with a simulated orthodontic model was undertaken to evaluate the effects of bracket width and ligation technique on the moment production of conventional and self-ligated brackets during axial rotation. Bracket widths ranged from 1.890 mm (0.0744 inch) to 2.809 mm (0.1106 inch). Steel tie, elastomeric, and self-ligating spring clip ligation techniques were used. Empirically, both bracket width and ligation technique significantly effect the moment produced during axial rotation. For the range of bracket widths and types evaluated, ligation technique was found to have a greater influence on moment production than did bracket width. The self-ligated spring clip bracket delivered the least force over the greatest range of axial rotation. PMID- 8362788 TI - Relationships between mandibular canine calcification stages and skeletal maturity. AB - Hand wrist radiographs and dental panoramic radiographs of 200 boys and 215 girls were assessed to determine the relationship between the developmental stages of the mandibular canine and skeletal maturity indicators of the pubertal growth spurt. Chi-square and Kendall's tau statistics demonstrated significant (P < 0.001) relationships between skeletal maturity indicators. Associations between canine development and skeletal maturity ranged from 0.53 to 0.85. Most children having attained canine stage G showed the presence of the adductor sesamoid (81%), capping of the diaphysis of the third middle phalanx (77%), and capping of the fifth proximal phalanx (87%). Growth reference data for American children suggest that stage G occurred approximately 0.4 years and 1.3 years before peak height velocity for girls and boys, respectively. It is indicated that canine calcification could serve as a useful tool for evaluating childrens' skeletal maturation and, by association, somatic maturity. PMID- 8362789 TI - Mandibular growth in patients with cleft lip and/or cleft palate--the influence of cleft type. AB - A total of 229 adult white patients with cleft lip or palate were evaluated, through cephalometric radiographs, to determine cleft-type influence on mandibular structure and spatial position. The sample includes adult patients with unilateral complete cleft lip and alveolus (n = 50), complete cleft lip and palate (n = 118), and isolated cleft palate (n = 61). A group of 65 subjects with normal occlusion and without cleft lip or palate was used as a control group. All groups were matched according to sex. When compared, the cleft groups and the normal group showed that the mandibular structure was significantly different. The mandible in the cleft groups displayed shorter mandibular ramus and body length, without difference between the cleft types. Mandibular position relative to cranial base was similar in the cleft groups with involvement of the palate, and differed significantly from that observed in the group with cleft lip and alveolus and in the subjects without cleft. Palatal clefts induce a significant downward and backward rotation of the mandible associated with a more obtuse gonial angle. Thus a small mandible is a structural characteristic of all cleft types studied. However, mandibular shape and spatial position are strongly influenced in clefts that involve the palate. PMID- 8362790 TI - Clinical versus quantitative assessment of headgear compliance. AB - This study was undertaken to determine if clinicians could accurately evaluate headgear compliance. Headgear timers were used covertly to quantitatively assess the headgear compliance of 28 patients over 3 consecutive months. Investigators subjectively evaluated the patients to determine how many hours per day they felt the patient had been wearing the headgear. Investigators were divided into three groups: (1) 5 orthodontists (2 board certified, 3 board eligible--total of 50 years of orthodontic experience); (2) 10 residents; and (3) 11 assistants. At least two investigators from each group evaluated the same person for all three appointments. The average error values were 2.86 hours, 3.27 hours, and 3.61 hours, respectively, for the three groups. The standard deviations were also very large, indicating that no group could accurately or consistently assess headgear wear. In this study no difference was found in compliance between sexes. Patients 10 to 12 years of age were more compliant than those 12 to 14 years of age, which were more compliant than the > 16 age group. The least compliant was the 14 to 16 year age group. PMID- 8362791 TI - An American Board of Orthodontics case report: the orthodontic-surgical correction of a Class I malocclusion with high mandibular plane angle, bimaxillary protrusion, and vertical maxillary excess. AB - This is the case report of a 26-year-old black woman with a Class I malocclusion and a skeletal Class II profile and vertical maxillary excess. Extraction spaces were closed, creating a Class II malocclusion to augment anticipated surgery (LeFort I osteotomy and genioplasty). The treatment result provided outstanding occlusal function and optimal facial esthetics. Attention to detail was mandatory, i.e., identify the patient's chief complaint, provide treatment options to resolve the complaint, and treat and maintain the dentition as ideally as possible. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirements for the certification process conducted by the Board.] PMID- 8362792 TI - An American Board of Orthodontics case report: treatment of a crowded Class II malocclusion in an adult. AB - A case report is presented of an adult with a crowded Class II, Division I subdivision left malocclusion. There was a moderate arch length deficiency in both arches. All four canines were prominent and had gingival recession. The patient's profile necessitated nonextraction treatment. Free gingival grafts were placed to prevent further recession and the Class II relationship and crowding were resolved with a positive profile change. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirements for the certification process conducted by the board.] PMID- 8362793 TI - Serious sports injuries requiring hospitalization seen in a pediatric emergency department. AB - OBJECTIVE: To define the spectrum of serious sports injuries requiring hospitalization seen in a pediatric emergency department. DESIGN: Trauma registry and retrospective chart reviews. SETTING: Emergency department, Children's Hospital, Boston, Mass. STUDY PARTICIPANTS: One hundred forty-two patients with sports injuries presenting to the emergency department and requiring hospitalization over 2 years. MEASUREMENTS/RESULTS: Serious sports injuries accounted for 13% of admissions for trauma, 0.6% of visits to the emergency department for trauma, and approximately 0.14% of total encounters. Injuries included fractures (77%), abdominal injuries (7%), multiple trauma (5%), cerebral contusions or hemorrhages (4%), and dislocations (3%). The most frequently injured areas were the extremities (69%), head and neck (16%), and abdomen (3%). Compared with nonsports injuries requiring hospitalization, sports injuries occurred in older patients (11.5 vs 7.3 years, P < .001) and more often in males (83% vs 64%, P < .001). Sports injuries also resulted in higher Injury Severity Scores (10 vs 8.8, P = .021) and in more fractures (77% vs 51%, P < .001) and neck injuries (4% vs 1%, P = .002). CONCLUSION: Serious sports injuries evaluated in the emergency department affect predominantly male teenagers and result predominantly in fractures involving the extremities. The spectrum of injuries is dissimilar to that resulting from other mechanisms. PMID- 8362794 TI - Radiological case of the month. Choledochal cyst. PMID- 8362795 TI - Pathological case of the month. Meningioangiomatosis. PMID- 8362796 TI - Pathological case of the month. Benign rheumatoid nodules. PMID- 8362797 TI - Picture of the month. Acute guttate psoriasis. PMID- 8362798 TI - Thyrotoxicosis presenting with seizures and coma in two children. PMID- 8362799 TI - Monitoring retinopathy of prematurity: a new form for the nursery. PMID- 8362800 TI - Kids are working. PMID- 8362801 TI - Hereditary angioedema: danazol therapy in a 5-year-old child. PMID- 8362802 TI - Hyponatremia and water intoxication. PMID- 8362803 TI - Perinatal acute scrotum: controversies in the management of torsion of the testis. PMID- 8362804 TI - Community response to medical need. PMID- 8362805 TI - Alarming heart rates. PMID- 8362806 TI - Dermatitis and nutritional deficiency. Another acrodermatitis enteropathica-like eruption. PMID- 8362807 TI - Aplastic anemia in neonatal lupus erythematosus. AB - OBJECTIVE: To describe an infant with neonatal lupus erythematosus associated with aplastic anemia. SETTING: The pediatric department in a tertiary-care hospital. INTERVENTIONS: Packed red blood cell transfusions and a 3-week course of high-dose steroid therapy. MEASUREMENTS/MAIN RESULTS: The patient presented with severe anemia and a circumscribed, reticular, macular rash on the face and neck at 5 months of age. Skin lesion biopsy revealed epidermic hyperkeratosis, hydropic degeneration of the basal layer, and deposition of immunoglobulins and granular C1q at the dermoepidermal junction. Ro/SS-A antibodies were present in the infant. BFU-E (erythroid progenitor burst-forming unit) colonies in bone marrow increased by about tenfold when suppressor CD8+ T lymphocytes were removed, indicating immune suppression of hematopoiesis. High-dose steroid therapy failed. The infant subsequently developed gram-negative sepsis, severe metabolic acidosis, and consumptive coagulopathy and died. CONCLUSIONS: Neonatal lupus erythematosus may present as part of a spectrum. The disease may range from mild and transient to a severe, life-threatening condition requiring immediate intervention, as in the case reported here. This is the first report of neonatal lupus associated with aplastic anemia due to immune-mediated suppression of hematopoiesis. PMID- 8362808 TI - The value of early treatment of deer tick bites for the prevention of Lyme disease. AB - OBJECTIVE: To determine if the early antibiotic treatment of deer tick bites prevented Lyme disease. DESIGN: Prospective, double-blind, placebo-controlled, antibiotic treatment. SETTING: Private practice in an area endemic for Lyme disease. STUDY PARTICIPANTS: Patients between 3 and 19 years of age who received antibiotic treatment within 3 days following a deer tick bite. INTERVENTIONS: Patients received an antibiotic or placebo and were followed up for stage I and II disease. All patients had blood drawn at the time of presentation and 6 weeks later for immunofluorescent antibodies (IFA). MEASUREMENTS/MAIN RESULTS: One patient in the placebo group developed clinical Lyme disease associated with an IFA titer of 1:32, considered weakly positive. Three other patients in the placebo group developed an IFA titer of 1:32; one had an influenzalike illness and two had no symptoms. None of the study patients developed any neurologic, cardiac, or arthritic symptoms in the 1- to 3-year follow-up. CONCLUSION: Based on the low frequency of illness, the absence of stage II disease, and the inability to establish the efficacy of early antibiotic treatment, we suggest that physicians not routinely use prophylactic antibiotics for deer tick bites. PMID- 8362809 TI - Granulomatous hepatitis in three children due to cat-scratch disease without peripheral adenopathy. An unrecognized cause of fever of unknown origin. AB - OBJECTIVE: To report the clinical experience of three patients with fever of unknown origin ultimately diagnosed as having cat-scratch granulomatous hepatitis in the absence of peripheral adenopathy. DESIGN: Case-control study. SETTING: Referral center at university-based referral practice. PATIENTS: Three children with fever of unknown origin. Follow-up following presentation was 6 months for each patient. MEASUREMENT AND RESULTS: All three patients with fever of unknown origin were diagnosed radiographically to have multiple hepatic defects. The defects were shown histologically to be granulomatous. Two of the three patients had Warthin-Starry staining bacilli in the granulomas consistent with a diagnosis of Afipia felis. All three had positive cat-scratch skin test results. CONCLUSIONS: Cat-scratch disease in the absence of peripheral adenopathy is a heretofore unrecognized cause of fever of undetermined origin and may account for a small, but significant, percentage of children presenting with it. PMID- 8362810 TI - Acrodermatitis enteropathica-like syndrome secondary to isoleucine deficiency during treatment of maple syrup urine disease. AB - We describe a patient with maple syrup urine disease in whom an acrodermatitis enteropathica-like syndrome developed while he was receiving a branched-chain amino acid-free formula. Iatrogenically induced isoleucine deficiency developed and resulted in a decreased protein accretion and persistent increase in the plasma concentrations of leucine. A rapid clinical response to isoleucine supplementation was noted. This observation underscores the risks of using amino acid-free formulas without adequate supplementation of deficient amino acids. PMID- 8362811 TI - Fanconi's syndrome with hepatorenal glycogenosis associated with phosphorylase b kinase deficiency. AB - OBJECTIVE: To describe two patients with Fanconi's nephropathy secondary to glycogen storage disease and speculate on the possible etiology. DESIGN: Convenience sample. SETTING: Tertiary care, referral center. PATIENTS: Two related children referred for failure to thrive, rickets, and hepatomegaly. INTERVENTION: Dietary and therapeutic measures for rickets and renal tubular acidosis. MEASUREMENTS AND RESULTS: The main laboratory findings were fasting hypoglycemia and massive glucosuria, with evidence of multiple renal tubular dysfunction characteristic of the Fanconi syndrome. Liver and kidney biopsy specimens were consistent with glycogen storage disease. Enzymatic assay of liver homogenates revealed marked deficiency of phosphorylase b kinase in one patient and absent activity in the other. CONCLUSION: Phosphorylase b kinase deficiency may be causally related to hepatorenal glycogenosis with the Fanconi syndrome. More patients with this syndrome need to be studied before a definitive causal role is implicated. PMID- 8362812 TI - Episodes of bradycardia during early infancy in the term-born and preterm infant. AB - OBJECTIVE: To document the incidence of transient episodes of bradycardia in a group of healthy term and preterm infants during the first 1 to 6 months of life. DESIGN: Longitudinal polysomnographic study. SETTING: Sleep laboratory in a university-affiliated urban medical center. PARTICIPANTS: Fourteen healthy term born infants, nine preterm infants with apnea in the nursery, and 10 preterm infants without apnea. Infants with neonatal morbidity except apnea were excluded. MEASUREMENTS: Transient episodes of bradycardia (< or = 100 beats per minute) were identified in 2- to 4-hour early evening polysomnographic tracings. The relationship with apnea, transcutaneous oxygen levels, and sleep state was determined. RESULTS: Transient episodes of bradycardia to 60 to 70 beats per minute were common, but there were no drops below 50 beats per minute. The incidence of transient episodes of bradycardia was inversely related to heart rate. Results for apneic and nonapneic premature infants were similar. CONCLUSIONS: Transient episodes of bradycardia are considered normal reflex responses and are not related to risk for sudden infant death syndrome. These results have implications for the setting of monitor alarms. PMID- 8362814 TI - The reliability of midstream urine culture from circumcised male infants. AB - The reliability of midstream urine culture from circumcised male infants was studied in 60 infants aged 1 to 21 weeks. A midstream urine specimen was collected after cleansing the penis. When the bladder was full again, a suprapubic bladder aspiration (SPA) was also performed. The results of the urine cultures were almost identical in specimens obtained midstream and by SPA. In 37 infants the cultures were sterile and in 13 positive, with the same microorganism being cultured in both instances. In one case, few colonies of Staphylococcus epidermidis grew only from the midstream culture. In nine infants, only midstream specimens were obtained because three attempts at SPA were unsuccessful. These results suggest that in circumcised male infants, the midstream method of obtaining urine for a culture is as reliable as SPA. PMID- 8362813 TI - Immunization status and reasons for immunization delay among children using public health immunization clinics. AB - OBJECTIVES: To determine whether children attending our local health department clinics were being immunized in a timely manner, and to investigate the reasons for children not being immunized on schedule. DESIGN: Cross-sectional research design. SETTING: Five Salt Lake City/County Health Department immunization clinics in Utah. PARTICIPANTS: All patients presenting to the clinics for immunization from November 1990 to March 1991 when minor illness is prevalent. INTERVENTIONS: Data were gathered through interview and questionnaire. MEASUREMENTS/MAIN RESULTS: Children were mostly white; they came from two-parent households with reasonably high incomes and high parental education level. Only four children were denied vaccination, all for inappropriate timing. None were denied for illness. More than 75% had postponed bringing their children in for immunization. The most common reason given for delay was minor illness in the child. CONCLUSION: Even in this "low-risk" population, parental misperception regarding immunizations is a significant, contributing factor to low immunization rates. Public educational programs directed at increasing parental knowledge must be developed. PMID- 8362815 TI - Acquired subglottic cysts in the low-birth-weight infant. Characteristics, treatment, and outcome. AB - OBJECTIVE: To provide a descriptive summary of characteristics, including demographics, symptoms, risk factors, and outcome of acquired subglottic cysts identified in the neonatal period. DESIGN: Patient series. SETTING: A tertiary neonatal care unit and referral neonatal follow-up clinic. PARTICIPANTS: One hundred seventy-four preterm infants undergoing flexible bronchoscopy, 21 (12%) referred for airway evaluation because of symptoms and 153 (88%) examined consecutively following 7 days or more of endotracheal intubation. INTERVENTION: None. MEASUREMENTS/RESULTS: Subglottic cysts were identified in 11 (7.2%) of 153 preterm infants examined prospectively at discharge from the neonatal intensive care unit after prolonged intubation and two (10%) of 21 infants referred for airway evaluation. Infants with subglottic cysts were extremely preterm (mean +/- SEM gestation, 26.7 +/- 0.5 weeks) and very low birth weight (894.6 +/- 64.6 g). The mean duration of intubation was 28.5 +/- 5.0 days. Most infants, particularly those with large cysts, were symptomatic with stridor, hoarseness, or obstructive apnea. In two cases, airway symptoms began after discharge from the neonatal intensive care unit. Ten (91%) of the 11 patients were discharged receiving home oxygen. Generally, multiple cysts were present in the subglottic space, most prominently located in the posterior aspect of the trachea. Three of five patients with large cysts received a tracheostomy. Two additional patients had surgical marsupialization of the cysts, and six others experienced resolution without treatment. One patient with large cysts died of viral pneumonia 10 months after surgical intervention. An additional patient with large cysts died before surgical intervention secondary to chronic lung disease and cor pulmonale. All surviving infants had resolution of signs of airway obstruction and 10 of the 11 did not require supplemental oxygen or have symptoms of chronic pulmonary disease at age 1 year. CONCLUSION: Intubation-acquired subglottic mucous cysts in the neonate may occur more commonly than was previously recognized. Symptoms of this lesion may mimic features of chronic lung disease. Early identification of the cysts with flexible bronchoscopy is important since airway compromise may progress and surgical intervention may be lifesaving. PMID- 8362816 TI - The morbidity of cardiac nondisease revisited. Is there lingering concern associated with an innocent murmur? AB - BACKGROUND: The phenomenon of cardiac nondisease was first reported in 1967 to call attention to the fact that some children were being restricted from their normal activities because their parents believed that they had a heart problem when, in fact, the child's heart was perfectly normal. This influential article and others have suggested that there may be significant morbidity in children who have been found to have innocent cardiac murmurs. METHODS: Parents of 71 schoolchildren were interviewed 1 to 5 years after their child had been examined by a pediatric cardiologist. Parents were asked about the presence of a family history of heart disease, their recall of the diagnosis and recommendations made by the cardiologist, and their level of satisfaction with the visit to the cardiologist. Parents were extensively questioned for evidence of restriction of the child's activities and for the presence of a belief that their child's murmur was something to still be concerned about. RESULTS: None of the parents reported restricting their child's activity, but 12 (17%) were still concerned about the murmur. A statistically significant relationship between parents reporting being less than "very satisfied" with the visit to the cardiologist and the presence of concern was found (P = .0006 by chi 2, Yates' correction). No other associations were noted. CONCLUSION: The association with a lower degree of satisfaction suggests that communication issues are relevant to the presence of lingering parental concern. Because the parents of a child with an innocent murmur may consider him or her to be "vulnerable," primary care physicians should follow up with parents of children referred to pediatric cardiologists for evaluation of a murmur so that any potential misunderstandings can be clarified. PMID- 8362817 TI - The art of referral. Pediatricians and the emergency department. PMID- 8362818 TI - First, do no harm. Low birth weight and adolescent obesity. PMID- 8362819 TI - Do primary care physicians prefer dictated or computer-generated discharge summaries? AB - OBJECTIVE: To determine the preference of primary care physicians for computer generated vs dictated discharge summaries from a neonatal intensive care unit. DESIGN: Survey mailed to primary care physicians. SETTING: Regional referral area of a level III neonatal intensive care unit. PARTICIPANTS: Pediatricians and family medicine physicians caring for infants discharged from the neonatal intensive care unit. RESULTS: Of 58 questionnaires sent, 45 (78%) were returned. Overall, 33 physicians (73%) either strongly or mildly preferred the computer generated discharge summary; eight (18%) had no preference; and four (9%) preferred the dictated discharge summary (P < .001). The category of strongest preference was relevance of information for continued patient care. Preference for type of discharge summary was not significantly influenced by time in practice, type of practice, preference to read or scan summaries, or frequency of computer use. CONCLUSION: Primary care physicians prefer computed-generated discharge summaries to dictated discharge summaries. PMID- 8362820 TI - An updated pediatric perspective on the Apert syndrome. AB - This review of the Apert syndrome, based on our research experience with 136 cases, provides a clinically relevant pediatric perspective. The brain is megalencephalic, resulting in a disproportionately high cranium and a mean birth length and weight above the 50th percentile. The growth pattern in childhood consists of a slowing of linear growth so that most values fall between the 5th and 50th percentiles. From adolescence to adulthood, slowing becomes more pronounced. Central nervous system abnormalities may occur in some cases, including malformations of the corpus callosum and limbic structures, gyral abnormalities, hypoplastic white matter, and heterotopic gray matter. Distortion ventriculomegaly is found because of the large brain in a misshapen skull. Progressive hydrocephalus is uncommon. Intelligence in patients with the Apert syndrome varies from normality to mental deficiency. Early release of the coronal suture and advancement and reshaping of the frontal bone reduce further dysmorphic and unwanted growth changes in the skull, but probably do not affect mentation. Associated cardiovascular and genitourinary anomalies occur in 10% and 9.6% of cases, respectively. Other important findings reviewed include upper- and lower-airway compromise, calvarial development, cervical vertebral anomalies, limb defects, ocular and otologic manifestations, and dermatologic characteristics. PMID- 8362821 TI - Medicine is a calling--not a business. PMID- 8362822 TI - Can we triage alcoholics with end-stage liver disease? PMID- 8362823 TI - Treatment of Crohn's disease with 5-ASA. PMID- 8362824 TI - Gastrointestinal toxicity of newer NSAIDs. AB - The linkage between gastroduodenal mucosal injury and nonsteroidal anti inflammatory drugs (NSAIDs) is now well established. Fifteen percent to 20% of patients taking these agents develop gastric or duodenal ulcer, and about 3% of this group goes on to experience hemorrhage or perforation. Gastrointestinal (GI) complications occur primarily in certain high risk groups, notably elderly female patients and patients with a prior history of peptic ulcer or GI bleeding. Recently, two new NSAIDs, nabumetone and etodolac, which are reportedly safer because they selectively inhibit prostaglandin synthesis in target tissues but spare that in the stomach, have been introduced in the United States. Further, data from clinical trials of oxaprozin, an NSAID not yet available in the United States, indicate that this agent may have a better safety profile than older NSAIDs. A review of the literature concerning the mucosal toxicity of these three agents reveals that the overall ulceration and major complication rate is low. However, a direct comparison with older NSAIDS in a large group of patients in a dose with similar efficacy is lacking. PMID- 8362825 TI - Clinical applications of electrogastrography. AB - Recently, electrogastrography (EGG) has received more and more attention. While gastroenterologists are interested in its clinical applications, concerns remain regarding the reliability and analysis of the EGG and the correlation between the EGG and gastric motility. The aims of this paper are to address these concerns and to review the potential clinical applications of the EGG. The following areas are discussed, based on the literature and our own experience with EGG: the refined method for the measurement of the EGG, the advanced techniques for quantitative analyses of the EGG, the reliability of the EGG in measuring gastric myoelectrical activity, the correlation between the EGG and gastric motility, and applications of the EGG in clinical gastroenterology. PMID- 8362826 TI - Liver transplantation for patients with alcoholism and end-stage liver disease. AB - Liver transplantation for alcoholic cirrhosis remains controversial. In particular, criteria for the selection of patients who will remain recovered from alcoholism post-transplant require better definition. We analyzed the long-term predictive value of categorizing transplant referral patients with alcoholism and end-stage liver disease into risk groups for recidivism and noncompliance. Forty seven patients with the diagnosis of alcoholism and advanced liver disease were evaluated and placed into predefined risk groups (low-, moderate-, and high-risk) for recidivism and noncompliance. No absolute period of abstinence from alcohol was required. All patients were asked to sign a contract not to drink alcohol and comply with a rehabilitation program before and after transplantation. Compliance with alcohol rehabilitation, abstinence, functional level, employment, and survival were assessed. Patients who were not compliant with the rehabilitation program or consumed alcohol were scored as failures. Thirty-one patients were ranked as low risk, and were accepted for liver transplantation; 27 patients were transplanted. Five of 31 patients (16%) drank alcohol. One patient drank before and four patients drank transiently after transplantation. Ten patients were categorized as moderate risk, and were deferred for transplantation; two patients underwent later transplantation. All 10 patients (100%) were noncompliant or drank alcohol, including two patients who drank after transplantation after a period of abstinence and rehabilitation. Six patients were ranked as high risk, and were denied liver transplantation. Five patients (83%) drank alcohol and were noncompliant. Minimum follow-up was 12 months (mean, 24 months; range, 12-41 months). The mean Karnofsky performance score was 34 before and 84 after liver transplantation. Actuarial survival of alcoholic patients undergoing transplantation was 93%. We conclude that categorization of transplant referral patients with alcoholism and liver failure into predefined risk groups for recidivism and noncompliance accurately predicts pre- and post-transplant behavior. As defined, only low-risk alcoholic patients are good candidates for liver transplantation. PMID- 8362828 TI - Prospective evaluation of optimal number of biopsy specimens and brush cytology in the diagnosis of cancer of the colorectum. AB - We prospectively studied the diagnostic accuracy of endoscopic biopsy and cytology in the diagnosis of colorectal cancer and sought to ascertain the optimal number of biopsy specimens that should be taken. Seventy consecutive patients with colorectal masses or polypoid lesions that could not be removed by endoscopic polypectomy and which were referred for surgery were studied. Lesions were first brushed for cytology. A series of 10 biopsies were then obtained from each lesion; the first four were placed into the first container, and two were placed into each of three other containers. Cytology and biopsies were read blindly by one pathologist. Findings were compared with the resection specimen results. Ten lesions were benign; all had negative biopsies and cytology. Sixty lesions were malignant: cytology was positive in 77.2% and biopsies in 78.3%. The yield was increased to 91.7% when both were done (cytology plus six biopsies). Cytology detected seven cancers that were missed by biopsy. Biopsy detected eight cancers not diagnosed by cytology. Five cancers were missed by both. Of the 47 cancers detected by biopsy, the first four biopsies made the diagnosis in 41 cases. Taking two more biopsies (six total) identified six more cancers. No additional cancers were identified by taking more biopsies (eight or 10 total). When six different biopsy-cytology strategies were examined: 1) cytology alone, 2) four biopsies (Bx), 3) six Bx, 4) 10 Bx, 5) cytology + four Bx, and 6) cytology + six Bx, the yield was 77.2%, 68.3%, 78.3%, 78.3%, 90.0%, and 91.7%, respectively. We conclude that biopsy and cytology are complementary in the diagnosis of colorectal cancer. The combination of cytology and four to six biopsies is recommended. There appears to be little additional yield to taking more than six biopsies. Even combined biopsy and cytology will miss 8-10% of cancers. PMID- 8362827 TI - Long-term management of Crohn's disease with mesalamine capsules (Pentasa). Pentasa Crohn's Disease Compassionate Use Study Group. AB - Current long-term treatment of Crohn's disease is unsatisfactory. Based on the Crohn's Disease Activity Index (CDAI), this multicenter trial enrolled patients with either active Crohn's disease (CDAI > or = 150) or disease in remission (CDAI < 150). The primary measure of therapeutic response was mean change in CDAI from baseline to final visit. All patients began treatment with a dosage of < or = 4 g/day of mesalamine that ranged from 3.7 g at baseline to 3.4 g at final visit. Overall, 467 patients were enrolled: 333 (active disease) and 134 (remission). The median study participation time was 14 months. For patients entering with active disease, the mean reduction in CDAI was 77 points, with 42% (122/289) achieving remission by their final visit. For patients entering in remission, there was an increase in mean CDAI from 90 at baseline to 96 at final visit, with 79% (95/120) of patients in remission at final visit and 72% (31/43) in remission continuously after 12 months of therapy. From baseline to final visit, the mean prednisone dose decreased 5 mg/day in patients with active disease and 11 mg/day in patients in remission. Mesalamine was well tolerated and no adverse laboratory trends were observed. These results suggest that controlled release mesalamine shows promise as a steroid-sparing agent and as a safe and effective long-term therapy for the induction of and maintenance of remission of mild-to-moderate Crohn's disease. PMID- 8362829 TI - Utility of endoscopic retrograde cholangiopancreatography in the evaluation of idiopathic abdominal pain. AB - We investigated the role of endoscopic retrograde cholangiopancreatography in 86 consecutive patients with idiopathic chronic or recurrent abdominal pain. There were 18 males and 68 females with a mean age of 48 yr. Forty patients (47%) had previous cholecystectomy. Patients were divided into two groups: group I (normal serum alkaline phosphatase and total bilirubin) (n = 52), and group II (elevated serum alkaline phosphatase and/or total bilirubin) (n = 34). Pancreatograms were normal in all patients, including five with pancreas divisum. Cholangiograms were abnormal in 10 of the 34 patients in group II (30%), and in only three of the 52 patients in group I (6%) (p = 0.003). Bile duct stones were present in 18% of the patients in group II, and in none of the patients in group I (p = 0.003). Of the 40 post-cholecystectomy patients, four patients had bile duct stones and five had common bile duct dilation without stones. However, no stones were found in any post-cholecystectomy patients with normal liver tests. Of the 46 patients with gallbladder in situ, two patients with abnormal liver tests had common bile duct stones and two patients had common bile duct dilation without stones. These results indicate that, among patients with idiopathic abdominal pain, cholangiography should be performed primarily in those with abnormal liver tests; however, further investigation with pancreatography is unnecessary. PMID- 8362830 TI - Long-term Helicobacter pylori recurrence after successful eradication with triple therapy. AB - To establish the rate of Helicobacter pylori recurrence after a standard triple therapy regimen (bismuth subsalicylate, tetracycline, metronidazole) and determine which clinical factors affect reinfection, we prospectively followed 118 patients after successful H. pylori eradication. Elimination of H. pylori was confirmed by repeat endoscopy and urea breath test 4 wk after completion of therapy. Serial [13C]urea breath tests were performed at 3-month intervals; antral biopsies were used to verify reinfection. Recurrence of H. pylori infection occurred in 4/118 (3.4%) patients. Three of the four relapses occurred in the 1st yr after treatment. Gender, age, ethnic group, alcohol consumption, cigarette use, and gastrointestinal diagnosis do not predict H. pylori recurrence. We conclude that the rate of recurrence after successful H. pylori eradication is low, and that when reinfection takes place, it occurs most commonly within the 1st yr after treatment. PMID- 8362831 TI - Gastric mucosal hydrophobicity and Helicobacter pylori: response to antimicrobial therapy. AB - The hydrophobic properties of the gastric mucosa are reduced by NSAIDs and by Helicobacter pylori infection. Our investigation was to determine whether this abnormality was due to the bacteria or to the inflammatory response. Contact angle measurements were made on gastric antral and corpus biopsies taken from 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after therapy. The contact angle improved steadily and statistically throughout the 2 weeks of therapy (for day 0, 3, 14, respectively) antral mucosa 54.2 +/- 2, 59.3 +/- 2, and 63.2 +/- 2; corpus mucosa 55 +/- 1, 57.8 +/- 3, and 66.6 +/- 1. After 2 days of therapy, H. pylori bacteria were no longer evident, and yet the contact angle continued to improve, suggesting that bacteria and bacterial products (e.g., lipases) may not be critical factors. H. pylori was eradicated in five and failed in five. One month after ending therapy, the contact angles of those with recrudescence of infection and those with eradication were similar and higher (p < 0.05) than before therapy (antrum: 69.8 +/- 1 vs. 71.1 +/- 2, corpus: 66.4 +/- 4 vs. 70.8 +/- 2) (p > 0.25 for both). We conclude that gastric surface hydrophobicity abnormalities do not appear to be directly related to the presence of H. pylori organisms or the histologic features of acute inflammation, but are responsive to antimicrobial therapy. PMID- 8362832 TI - Evaluation of new therapy for eradication of H. pylori infection in nude mouse model. AB - OBJECTIVES: developing a new therapy for eradication of H. pylori by using the nude mouse model. METHODS: By quantifying the number of colonies of Helicobacter pylori and the score of H. pylori-associated gastritis from the gastric tissue following different drug regimens in inoculated nude mice, we evaluated the effectiveness of each regimen, including a new drug, plaunotol. Drugs were administered daily for a 1-wk period, beginning 4 wk after inoculation. RESULTS: In the examination after therapy, the number of colonies of H. pylori and the score of gastritis in the triple-therapy group were significantly lower than in any of the singly- and dual-drug groups or control group from 5 wk to the end of the study after inoculation. Inflammation of the stomach was less apparent in the treatment groups than in the control group. CONCLUSION: With the nude mouse model, we quantitatively demonstrated that the new triple therapy is the most effective therapy for eradication of H. pylori. PMID- 8362833 TI - Helicobacter pylori and intestinal metaplasia: comparison between British and Yemeni patients. AB - There have been suggestions linking gastric carcinoma with Helicobacter pylori on the one hand and type III intestinal metaplasia on the other hand. This study was aimed at investigating the relationship between intestinal metaplasia and its subtypes, and the presence or absence of H. pylori in gastric biopsies from two geographically different patient populations, one with a much higher prevalence of H. pylori than the other. Antral biopsies from 179 British and 123 Yemeni patients with dyspepsia were examined. Sections stained with hematoxylin and eosin, Alcian blue/periodic acid-Schiff, high iron diamine/Alcian blue, and Warthin-Starry stains were used to assess the presence or absence of inflammation, H. pylori, and intestinal metaplasia with its three subtypes. Although Yemeni patients had a significantly higher prevalence of H. pylori than British patients (113/123. 92% vs. 83/179, 46% respectively; p < 0.001), Yemeni patients had a significantly lower prevalence of all types of intestinal metaplasia (23/123, 19% vs. 60/179, 34%; p < 0.001), as well as type III metaplasia (4/123, 3% vs. 39/179, 22%, p < 0.001). These trends persisted when only patients above the age of 40 yr were considered. However, in British patients, intestinal metaplasia was more commonly seen in those with H. pylori than in those without (36/83, 43%, and 24/96, 25%, respectively, p < 0.01), although the prevalence of type III metaplasia was not significantly different in the two groups (23/83, 28% vs. 16/96, 17%, respectively). The contrasting findings in the two patient populations suggest the presence of other factors, possibly genetic, which control the development of intestinal metaplasia and possibly gastric carcinoma in H. pylori-positive patients. PMID- 8362834 TI - Premature lower esophageal sphincter closure as a cause of dysphagia. AB - Impaired lower esophageal sphincter (LES) relaxation is highly correlated with dysphagia. A variation of the impaired relaxation of the LES of achalasia has been described, characterized by premature closure after normal relaxation. With a microtransducer system, standard manometric testing followed by food ingestion identified 33 patients (12 male, 21 female, 18-79 yr old) who exhibited premature LES closure. Twenty-three (70%) of these patients had a presenting complaint of dysphagia. Of these, seven (30%) experienced dysphagia during food ingestion. Manometry documented a concurrent motor abnormality in the esophageal body in 28 (85%) patients. Of the five remaining patients who did not have a concurrent motor abnormality, all had a presenting complaint of dysphagia, and three (60%) experienced dysphagia during food ingestion. The incidence of dysphagia during testing reported by patients with premature LES closure is comparable to that reported by patients with achalasia (45%) or diffuse esophageal spasm (38%) who have been studied during food ingestion in our laboratory. PMID- 8362835 TI - Esophageal dilation with polyvinyl bougies, using a marked guidewire without the aid of fluoroscopy: an update. AB - One hundred thirty-eight patients with esophageal stricture underwent polyvinyl bougie dilations whereby American Endoscopy dilators were passed over a marked guidewire that had been placed endoscopically. Fluoroscopy was not utilized during the dilations. The dilations were performed only after the guidewire was properly placed, with 60-cm markings at the incisors, which ensured that the tip of the guidewire was in the antrum. One hundred fourteen patients had benign strictures and 24 had malignant strictures. There were 197 sessions of dilations for a total of 748 individual dilations. In 97 of 138 patients, the guidewire was placed in the antrum under direct vision. The remaining 41 patients had significant esophageal stenosis which prevented passage of the endoscope into the stomach; therefore, the guidewire was placed by advancing it blindly through the stenosis. There were no procedure-related complications. During this period, eight patients were dilated without complications, using fluoroscopic placement of guidewire because endoscopic placement of the guidewire was not considered safe. We conclude that esophageal strictures can be safely dilated in most patients by means of the American Endoscopy dilator system and the marked guidewire without the aid of fluoroscopy. PMID- 8362836 TI - Abnormal gallbladder function in patients with irritable bowel syndrome. AB - Abnormalities of the autonomic nervous system function and cholecystokinin release have been described in patients with irritable bowel syndrome. Because the autonomic nervous system and cholecystokinin have an important role in the normal functioning of the gallbladder, we studied gallbladder contraction in response to a meal, using real time ultrasonography in irritable bowel syndrome patients (n = 20) and healthy controls (n = 15). The following parameters were studied: 1) fasting gallbladder volume, 2) residual volume after maximal contraction and at the end of 2 h, 3) maximum percent of gallbladder emptied, and 4) the time taken for maximal contraction. Fasting gallbladder volume (26.21 +/- 1.81 ml vs 15.21 +/- 1.63 ml, p < 0.001), and residual volume after maximal contraction (14.2 +/- 1.69 ml vs. 5.86 +/- 0.98 ml, p < 0.001) and at the end of 2 h (18.81 +/- 1.73 ml vs. 11.65 +/- 1.45 ml, p < 0.01) were significantly higher in the patient group, compared with controls. The maximum emptying was less (49.55 +/- 2.75% vs. 63.98 +/- 4.55%, p < 0.01) and the time taken for maximal contraction (59.25 +/- 3.8 min vs. 42.33 +/- 2.04 min, p < 0.001) was longer in the patient group than in the controls. Based on these observations, we conclude that patients with irritable bowel syndrome have significant abnormalities of gallbladder motor function. PMID- 8362837 TI - Does use of the Coloscreen Self-Test improve patient compliance with fecal occult blood screening? AB - Occult blood-screening methods which do not require stool manipulation have been devised in an attempt to improve patient compliance with fecal occult blood testing. We performed a randomized, prospective study comparing patient compliance with the Coloscreen Self Test, a fecal occult blood detection method which does not require stool manipulation, and standard guaiac-impregnated cards in a VA clinic and a university-based private practice to determine whether the Coloscreen Self-Test would improve patient compliance with fecal occult blood testing. Overall, there was no significant difference in compliance between the two tests, with a compliance of 71% (105/147) for the guaiac cards and 60% (88/136) for the Coloscreen Self-Test (p = 0.49). However, multiple logistic regression showed that, when using the Coloscreen Self-Test, patients at the VA clinic had significantly reduced compliance. Only 46% (23/50) returned the Coloscreen Self-Test compared with 84% (42/50) who returned the guaiac cards (p < 0.05). We conclude that the Coloscreen Self-Test does not improve patient compliance with fecal occult blood testing, and may reduce compliance in some sectors of the population. PMID- 8362838 TI - The morphologic relationship of sinus and fistula formation to intestinal stenoses in children with Crohn's disease. AB - Sinus and fistula (SF) formation in adults with Crohn's disease has been ascribed to increased intraluminal pressure from stenotic lesions or to inflammation. We retrospectively evaluated 55 surgically resected specimens from 30 children with Crohn's disease for stenotic lesions, sinuses, fistulas, and inflammation. Eighteen of 30 children had one operation, and there were 12 multiple surgeries. Thirty-one of 55 specimens (56%) contained stenoses. SF formation was seen in 16 of 31 specimens with stenosis; it developed proximal to the stenosis in seven patients, distal in five, and both proximal and distal in four. SF formation was also noted in 12/24 specimens without stenosis. In 93% of the cases, the SF was associated with moderate to severe inflammation. Although 56% of the patients had stenoses, SF frequently developed independent of stenosis. All SF were associated with inflammation. Therefore, inflammation rather than increased intraluminal pressure appears to be the primary factor in SF formation in children with Crohn's disease. PMID- 8362839 TI - Recurrent gallstone formation after successful extracorporeal shock-wave lithotripsy. AB - Gallstone recurrence was evaluated in 184 patients exhibiting complete stone disappearance after successful extracorporeal shock-wave lithotripsy (ESWL) and concomitant oral bile acid therapy. Follow-up examinations conducted 6-43 months after termination of adjuvant bile acid therapy revealed recurrent calculi in 40/184 (21.7%) patients (27 females, 13 males, p < 0.01; 13 patients with solitary, 27 patients with multiple stones) after a median stone-free period of 11 months (range 1-33 months; mean +/- SD, 13 +/- 8 months). Therefore, an overall probability of stone recurrence of 11.8% was observed 12 months after complete stone disappearance had been confirmed sonographically and bile salt therapy terminated, and a probability of 25.5% after 24 months. Gallstone reformation occurred in 30/146 (20.5%) patients with initially solitary and 10/38 (26.3%) patients with multiple calculi [not significant (NS)]. Only 3/40 (8%) patients with recurrent calculi reported biliary colic. Sonographic gallbladder contractility values acquired at the time recurrent stones were detected did not show any significant differences, compared with the data obtained in the pretreatment examinations; neither were any differences noted between the patients with gallstone reformation and those who remained stone-free. In 20/33 (61%) patients with recurrent stones who opted for further conservative retreatment (ESWL and/or oral litholysis), complete stone disappearance was achieved a second time. The recurrence rates achieved within the first 3 yr after successful shock-wave lithotripsy of biliary calculi cover a range similar to the rates noted after dissolution therapy. PMID- 8362840 TI - Obesity and weight reduction do not influence gastric emptying and antral motility. AB - A dual radioisotope technique was used to measure gastric emptying of a mixed solid and liquid meal in 30 obese (> 125% of ideal body weight) subjects and 23 age- and sex-matched nonobese control subjects. Gastroduodenal motility studies were also performed on seven obese and 10 nonobese subjects to compare postprandial antral motility. In addition, eight obese subjects underwent gastric emptying studies before and after substantial weight reduction (mean 8.3%). Gastric emptying of both solids and liquids was similar in obese and nonobese subjects, and antral motility indices did not differ between the groups. Gastric emptying rates before and after substantial weight reduction were similar. We conclude that neither gastric emptying nor antral motility appear to be abnormal in morbidly obese subjects; neither does gastric emptying appear to be affected by substantial acute weight reduction. PMID- 8362841 TI - Endoscopic diagnosis and resection treatment for flat adenoma with severe dysplasia. AB - In a prospective study from 1988 to 1991, we discovered 31 flat colon adenomas in 29 patients and performed endoscopic resection of 27 of these lesions, using the strip biopsy technique. All of these lesions were safely and completely resected even in the thin walls of the colon. All 27 lesions were histologically flat adenomas confined to the mucosa, with a maximum diameter of 3-20 mm. Thirteen were identified as severe dysplasia, three as moderate dysplasia, and 11 as mild dysplasia. These lesions were more clearly defined after they were sprayed with indigo carmine endoscopically. The 13 flat adenomas with severe dysplasia were morphologically slightly depressed red lesions with elevation of the surrounding mucosa (six lesions) and flat round red lesions with no changes in the surrounding mucosa (seven lesions). Due to the high incidence of severe dysplasia found in flat adenomas, removal using strip biopsy is recommended. PMID- 8362842 TI - Octreotide in the treatment of bleeding due to angiodysplasia of the small intestine. AB - Three patients with a history of bleeding due to small bowel angiodysplasia (repeated melena or occult fecal blood with serious anemia) were treated for 10 40 months with octreotide, a somatostatin analog that reduces the splanchnic flow. A dose of 0.1 mg subcutaneously twice a day was followed by an increase in hemoglobin, and reduction or elimination of the need for transfusions. There were no further melena episodes, and stool hemoglobin became stably negative in two cases. Suspension of the drug after 6 months in one case was followed by renewed bleeding, and resumption led to a further response. Lower doses tried in another case were ineffective. Although these uncontrolled clinical cases do not prove its efficacy, octreotide appears to be beneficial in the control and prevention of bleeding due to diffuse small bowel angiodysplasia. There is no evidence that it results in regression of angiodysplasias, as they persisted in the patient subjected to control jejunoileoscopy. PMID- 8362843 TI - Impact of stress on serum gastrin in Zollinger-Ellison syndrome. AB - We report an impressive case with Zollinger-Ellison syndrome (ZES), in which stress-induced sympathetic discharge influenced serum gastrin. Our patient was a 35-yr-old female who complained of frequent and massive vomiting (more than 4000 ml of gastric juice) which was aggravated especially by psychosocial stress. Basal hypergastrinemia (1900 pg/ml) was found after the admission. The most striking finding was that laboratory stress dramatically increased serum gastrin (from 1900 to 5400 pg/ml) and plasma noradrenaline (from 180 to 1130 pg/ml). Mental arithmetic stress further enhanced hypergastrinemia (5800 pg/ml) with a concomitant increase in plasma noradrenaline (1240 pg/ml). Neostigmine (10 micrograms/kg im) also increased serum gastrin up to 6100 pg/ml but propranolol (40 micrograms/kg i.v.) reduced these elevations (noradrenaline: 990 pg/ml, gastrin: 5000 pg/ml). In this case, the effect of stress on serum gastrin mimicked the effect of catecholamine infusion in ZES. These findings suggest that psychological stress induces serum gastrin secretion via beta-adrenoceptor with exacerbation of symptoms in some cases with ZES. PMID- 8362844 TI - A case of radical resection for solid cystic tumor of the pancreas with widespread metastases in the liver and greater omentum. AB - Solid cystic tumor (SCT) of the pancreas is known to be a low-grade malignant tumor and distant metastasis is very rare. A 50-year-old Japanese female was hospitalized because of a large mass in the upper abdomen. Computerized tomography revealed a large calcified tumor in the body-tail of the pancreas, and multiple liver tumors. Abdominal angiography demonstrated the pancreatic tumor and multiple hepatic tumors as a hypervascular mass, and disclosed a small tumor stain in the branch of the right gastroepiploic artery. The patient underwent a distal pancreatectomy with splenectomy, extended right hepatic lobectomy, and removal of the omental metastases. Histopathological and electron microscopic studies made a definitive diagnosis of SCT. She is well without any signs of tumor recurrence 1 yr and 2 months after the operation. This may be the first patient receiving simultaneous radical resection for both the main tumor and widespread distant metastases. PMID- 8362845 TI - Hepatic and pancreatic involvement in systemic amyloidosis. PMID- 8362846 TI - Diffuse gastrointestinal dysmotility in a patient with rheumatoid arthritis. PMID- 8362847 TI - Diagnostic endoscopy via gastrostomy or PEG stoma. PMID- 8362848 TI - Acute gastrointestinal hemorrhage from non-Hodgkin's lymphoma of the jejunum after orthotopic heart transplantation. PMID- 8362849 TI - Pancreatic pseudocysts involving both hepatic lobes. AB - We report a patient who developed pancreatic pseudocysts involving both hepatic lobes, after an episode of alcoholic pancreatitis. The possible routes by which pancreatic secretions may reach the liver, as well as diagnostic and therapeutic approaches, are discussed. PMID- 8362851 TI - Embolization therapy for lower GI bleed: benefit or "bombs away"? PMID- 8362850 TI - Inflammatory pseudotumor of the liver in a patient with chronic sclerosing cholangitis. AB - Inflammatory pseudotumor of the liver (IPL) is a rare fibro-inflammatory mass of unknown etiology, resembling a neoplasm. We report the occurrence of such a lesion in a young male Cambodian refugee to Canada who had a history of chronic cholangitis. Imaging studies suggested an intrahepatic abscess. Our report suggests that the lesion in this patient may have resulted from chronic portal pyemia. PMID- 8362852 TI - Unlocking the mysteries of portal hypertensive gastropathy. PMID- 8362853 TI - Response to Dr. Robert Fitzgibbons' editorial on laparoscopic cholecystectomy: the procedure of choice for acute cholecystitis. PMID- 8362854 TI - Corrugated ringed esophagus. PMID- 8362855 TI - A multicenter, randomized, controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis. PMID- 8362856 TI - Chyloperitoneum associated with sarcoidosis. PMID- 8362857 TI - Liver dysfunction caused by parvovirus B19. PMID- 8362858 TI - Caffeine withdrawal, metoclopramide, and depression. PMID- 8362859 TI - Gastric toxoplasmosis in the acquired immunodeficiency syndrome. PMID- 8362860 TI - Endothelin level in human ascitic fluid. PMID- 8362861 TI - Is taurine effective for treatment of painful muscle cramps in liver cirrhosis? PMID- 8362862 TI - National survey shows rise in drug use among young secondary school students. PMID- 8362863 TI - Cigarette smoking rate stabilizes after years of decrease. PMID- 8362864 TI - Physicians say direct-to-consumer advertising affects patient behavior. PMID- 8362866 TI - Forming a student hospital pharmacy society. PMID- 8362865 TI - Family and Medical Leave Act of 1993. PMID- 8362867 TI - Planning for simultaneous vacations. PMID- 8362868 TI - Visual compatibility of premixed theophylline or heparin with selected drugs for i.v. administration. PMID- 8362869 TI - Drug allergies, adverse drug reactions, and the patient record. PMID- 8362870 TI - ASHP national survey of hospital-based pharmaceutical services--1992. AB - The results of a national mail survey of pharmaceutical services in community hospitals conducted by ASHP during summer 1992 are reported and compared with the results of earlier ASHP surveys. A simple random sample of community hospitals (short-term, nonfederal) was selected from community hospitals registered by the American Hospital Association. Questionnaires were mailed to each director of pharmacy. The adjusted gross sample size was 889. The net response rate was 58% (518 usable replies). The average number of hours of pharmacy operation per week was 105. Complete unit dose drug distribution was offered by 90% of the respondents, and 67% offered complete, comprehensive i.v. admixture programs. A total of 73% of the hospitals had centralized pharmaceutical services. Some 83% provided services to ambulatory-care patients, including clinic patients, emergency room patients, patients being discharged, employees, home care patients, and the general public. A computerized pharmacy system was present in 75% of the departments, and 86% had at least one microcomputer. More than 90% participated in adverse drug reaction, drug-use evaluation, drug therapy monitoring, and medication error management programs. Two thirds of the respondents regularly provided written documentation of pharmacist interventions in patients' medical records, and the same proportion provided patient education or counseling. One third provided drug management of medical emergencies. One fifth provided drug therapy management planning, and 17% provided written histories. Pharmacokinetic consultations were provided by 57% and nutritional support consultations by 37%; three fourths of pharmacist recommendations were adopted by prescribers. A well-controlled formulary system was in place in 51% of the hospitals; therapeutic interchange was practiced by 69%. A total of 99% participated in group purchasing, and 95% used a prime vendor. The 1992 ASHP survey revealed a continuation of the changes in many hospital-based pharmaceutical services documented in earlier surveys (e.g., growth in clinical services, ambulatory-care services, computerization) and identified static areas that merit the attention of pharmacy leaders (e.g., provision of complete, comprehensive i.v. services). PMID- 8362871 TI - Leaching of diethylhexyl phthalate from polyvinyl chloride containers by selected drugs and formulation components. AB - The extent of leaching of diethylhexyl phthalate (DEHP) from polyvinyl chloride (PVC) bags by several organic solvents and surfactants used as formulation components and by 12 drug products containing these solvents and surfactants was studied. The organic solvents ethanol, polyethylene glycol, and propylene glycol, the surfactants polysorbate 80 and polyoxyethylated castor oil, and the 12 drugs were admixed separately in PVC bags of 5% dextrose injection. At the time of preparation and after 4, 8, and 24 hours at 24 degrees C, the concentration of DEHP in duplicate samples was determined in duplicate by high-performance liquid chromatography. Ethanol, polyethylene glycol, and propylene glycol at concentrations of 25% and the drugs containing these components did not leach DEHP within the study period. Polysorbate 80 1% to 25% leached detectable amounts of DEHP in as little as one hour at the high concentration and within four hours at the lower concentrations; at 24 hours, DEHP concentrations ranged from 36 micrograms/mL for 1% polysorbate 80 to 237 micrograms/mL for 25% polysorbate 80. Similar results were observed for polysorbate 80 plus ethanol and for polyoxyethylated castor oil plus ethanol. Drug products containing surfactants, including cyclosporine, miconazole, and teniposide, and the vehicles used in formulating taxol and taxotere, leached relatively large amounts of DEHP in 24 hours. Smaller amounts were leached by chlordiazepoxide hydrochloride and etoposide. DEHP was leached from PVC containers by a variety of surfactants and drug products containing these surfactants. Drugs that leach DEHP should be prepared in non-PVC containers and administered through non-PVC tubing. PMID- 8362872 TI - Compatibility and stability of ondansetron hydrochloride, dexamethasone, and lorazepam in injectable solutions. AB - The stability of ondansetron hydrochloride, dexamethasone sodium phosphate, and lorazepam in 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) minibags and glass bottles was studied. Triplicate solutions of 8 or 32 mg of ondansetron (as the hydrochloride salt) mixed with 20 mg of dexamethasone phosphate (as the sodium salt) with or without 2 mg of lorazepam were compounded in 50-mL PVC minibags and glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection and stored at 23-25 degrees C. Duplicate measurements were performed when drugs were added and at 1, 2, 4, 8, and 24 hours after addition. Samples of the 32-mg ondansetron admixtures were collected under aseptic conditions to inspect for precipitation and to count particles with a laser particle analyzer. Samples of all admixtures were evaluated for chemical stability by stability-indicating high-performance liquid chromatography. Ondansetron hydrochloride and dexamethasone were physically compatible and chemically stable for up to 24 hours under the study conditions. The concentration of lorazepam in PVC containers dropped below 90% of the original concentration within four hours. In addition, particle counts in lorazepam-containing solutions were higher when 0.9% sodium chloride injection was the diluent than when 5% dextrose injection was the diluent. In admixtures containing all drugs, ondansetron hydrochloride and dexamethasone sodium phosphate in 5% dextrose injection or 0.9% sodium chloride injection were stable for up to 24 hours when stored in PVC bags or glass bottles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8362873 TI - Converting from a hospital mainframe to a pharmacy stand-alone system. PMID- 8362874 TI - Converting from a hospital mainframe to an interim stand-alone system in a home infusion company. PMID- 8362875 TI - Changing to a new vendor and new hospital information system. PMID- 8362876 TI - Converting from manual to computerized medication administration records. PMID- 8362877 TI - Improving drug use through purchase agreement commitments. PMID- 8362878 TI - Diagnoses and prescribing for pediatric patients at two hospitals in Harare, Zimbabwe. PMID- 8362879 TI - Optically scannable form for documenting pharmacists' patient-care activities. PMID- 8362880 TI - Pharmacist liability. AB - The various legal theories under which pharmacists may be found liable are reviewed. The pivotal element in determining pharmacist malpractice is the study that was owed to the patient. A pharmacist's principal duties to the patient are to dispense the correct drug and to label it correctly; failure to fulfill either of these responsibilities had led to successful claims of malpractice. There have been only a few cases in which the court ruled that the pharmacist had a duty to warn the patient about a potential adverse drug effect or interaction. However, as the role of the pharmacist expands, more courts may begin to find pharmacists liable for failing to warn the patient under specific circumstances. Pharmacists have a heightened duty to warn the patient about potential problems associated with nonprescription drugs that they recommend. A pharmacist may escape liability if there was a lack of proximate cause. Similarly, the defenses of contributory or comparative negligence and voluntary assumption of risk are based on some conduct by the plaintiff that negates or modifies the pharmacist's negligence. Statutes of limitation can also exclude liability. Courts have not found pharmacists liable under strict liability theories. A breach of warranty claim has rarely been successful. Pharmacists could be found liable for negligent selection of therapeutic alternatives but probably not for injuries allegedly caused by correctly selected equivalent agents. Although no cases have been reported, pharmacists could be subjected to negligence-based liability for nondistributive pharmaceutical services. As pharmacists assume more responsibilities, pharmacist malpractice law will expand. PMID- 8362881 TI - Hospital's obligation to monitor medical services. Thompson v. Nason Hospital. PMID- 8362882 TI - Draft technical assistance bulletin on quality assurance for pharmacy-prepared sterile products. American Society of Hospital Pharmacists, Council on Professional Affairs. PMID- 8362883 TI - Draft guidelines on compounding of nonsterile products in pharmacies. American Society of Hospital Pharmacists. PMID- 8362884 TI - ASHP technical assistance bulletin on pharmacy-prepared ophthalmic products. American Society of Hospital Pharmacists. PMID- 8362886 TI - Biologic response modifiers: Clinical effects and pharmacoeconomic issues. PMID- 8362885 TI - An outpatient pharmacy services benefit in a reformed health care system. Coalition for Consumer Access to Pharmaceutical Care. PMID- 8362887 TI - Reimbursement and pharmacoeconomic perspectives in biotechnology. AB - Problems associated with reimbursement for biotechnology agents and strategies for solving these problems are reviewed. Because of the many different insurers in the U.S. health care system, a variety of reimbursement strategies have been developed for the biotechnology drugs that are now reaching the market. These strategies can vary by insurer, contract, treatment setting, and patient condition. With the advent of high-cost biotechnology drugs, pharmacists have taken on the additional roles of institutional educators and reimbursement specialists. Case studies involving three biotechnology agents illustrate how insurers deal with reimbursement for these drugs. Thrombolytic agents are reimbursed under Medicare, but the diagnosis-related-group (DRG) payment for myocardial infarction was not changed until two years after alteplase was marketed. Septic shock therapies potentially face similar reimbursement problems, which are compounded because the drugs can be lifesaving--leading to longer hospital stays. When filgrastim is administered, the amount reimbursed depends on the treatment setting. When claims for biotechnology agents are denied, the institution or provider should contact the payer to provide the needed information (in the case of missing information) or to discuss payer policies that may need review. Through proper case management, pharmacists and other institutional personnel can ensure reimbursement for these lifesaving biotechnology therapies. PMID- 8362888 TI - Strategic management of biotechnology agents. AB - The use of biologic response modifiers to demonstrate a value-driven approach to strategic management by pharmacists is described. To participate in decisions on the use of technology in their institutions, pharmacists must practice strategic management. This process includes environmental scanning, analysis of clinical and pharmacoeconomic data, and development of clinical management approaches. It is ideal for analyzing biologic response modifiers such as filgrastim and sargramostim. Emphasis must be placed on maximizing the fit among the products, the institution, and the health care environment. Pharmacists will find plentiful opportunities for clinical management with biotechnology agents. Practitioners who specialize in determining the total cost of care by using pharmacoeconomic methods are needed, as are practitioners trained to monitor the complicated biotechnology agents. Also, the institution needs to forecast accurately the impact of emerging biotechnology agents. If pharmacists can develop and control clinical, pharmacoeconomic, and reimbursement information databases for biotechnology agents, the pharmacy profession will be in a strong position to meet the challenges of biotechnology and realize the inherent opportunities. PMID- 8362889 TI - Overview of the immune and hematopoietic systems. AB - Current knowledge of the immune and hematopoietic systems is reviewed. All blood cells are derived from the totipotent stem cell, also known as the pluripotent stem cell. The differentiation of pluripotent peripheral stem cells into blood cells is controlled by a variety of biologic response modifiers, including colony stimulating factors (CSFs) and interleukins. Among the known CSFs are stem cell growth factor, granulocyte-macrophage CSF, multilineage CSF (interleukin-3), granulocyte CSF, macrophage CSF, and erythropoietin. CSFs are categorized as class I (those that stimulate the production of several types of blood cells; also called pluripotent) and class II (those that stimulate only one cell line; also called unipotent). Effects of CSFs can be studied using laboratory tests of colony-forming-unit activity. Pathogens entering the body through damaged skin or mucous membranes are met with both a cellular response (neutrophils, macrophages, cytotoxic T lymphocytes, and natural killer cells) and a humoral response (antibodies and complement). There is interplay between these two arms of the immune system to defend against foreign antigens. This interplay can occur by cell-to-cell contact and by cytokines. Hematopoietic and immune cells of the body are produced and destroyed under precise control of many different biologic response modifiers, including the colony-stimulating factors, interleukins, and interferons. PMID- 8362890 TI - Case report: hypothalamic tuberculoma associated with secondary panhypopituitarism. AB - Tuberculosis of the central nervous system remains quite rare in developed countries, accounting for only 0.53% of cases of tuberculosis in the United States. The most common form of intracranial tuberculosis is tuberculous meningitis; however, involvement may also take the form of a solid granulomatous mass (tuberculoma), which accounts for 15% to 30% of the neurosurgical cases in developing countries. An unusual case of a hypothalamic tuberculoma is presented in a man, who initially presented with signs and symptoms consistent with panhypopituitarism. Brain biopsy on two occasions confirmed caseating granuloma, and treatment with several antituberculous medications led to clinical improvement and radiographic resolution of the disease. PMID- 8362891 TI - Acute lung injury: what have we learned from animal models? AB - In 1950, Carl John Wiggers, philosopher and physiologist, wrote, "Reactions to definite types of stimulation may be observed or recorded, and concealed phenomena may be revealed by the use of apparatus that transforms them into forms that are recognizable by human senses. But complete understanding of physiological reactions often necessitates extensive operative procedures and sometimes the ultimate sacrifice of life. For this reason experimentation on animals is indispensable." Acute lung injury is still a significant cause of death in the developed world, and modern pharmacology and intensive care have failed to alter the clinical course of this complex condition. In the past decade, there was an explosion in understanding of the pathophysiology of acute lung injury, and with this has come the development of a new generation of agents that may provide a tool with which to combat this disorder. Use of animal model systems led to this greater understanding and is currently at the heart of evaluating the new therapeutic agents. This review briefly addresses the contribution animal model systems have made to what appear to be a watershed in attempts to obviate the effects of this mortal condition. PMID- 8362892 TI - Obesity and the heart. AB - Obesity can result in alterations in cardiac structure and function even in the absence of systemic hypertension and underlying organic heart disease. Increased total blood volume creates a high cardiac output state that may cause ventricular dilatation and ultimately eccentric hypertrophy of the left (and possibly the right) ventricle. Eccentric left ventricular (LV) hypertrophy produces diastolic dysfunction. Systolic dysfunction may ensue due to excessive wall stress if wall thickening fails to keep pace with dilatation. This disorder is referred to as obesity cardiomyopathy. The presence of systemic hypertension in obese individuals facilitates development of LV dilatation and hypertrophy. Congestive heart failure may occur in such individuals, and may be attributable to LV diastolic dysfunction or to combined LV diastolic and systolic dysfunction. The sleep apnea/obesity hypoventilation syndrome occurs in 5% of morbidly obese individuals and is potentially life-threatening. Treatment of obesity cardiomyopathy consists of weight loss, salt restriction, and diuretics. Digitalis and vasodilators may be useful in selected cases. Central obesity is probably a risk factor for the development of coronary heart disease. Alterations in lipid and insulin metabolism may facilitate development of coronary heart disease in obese patients. PMID- 8362893 TI - Current physician screening and treatment of hypercholesterolemic patients. AB - To determine resident physician recognition and treatment of hypercholesterolemia, a retrospective chart audit was performed on 300 systematically selected patients seen in an internal medicine resident's continuity care clinic during the spring of 1992. A self-administered resident survey was given after completion of chart selection. Of the 300 patients, 64 (21%) did not have a cholesterol reading on the chart. The frequency of screening was unaffected by cardiac risk factors, patient race or sex, or resident level of training or specialty. Of the 96 patients who had a total cholesterol greater than 240 mg/dL documented in the chart, 48% received diet therapy, 46% received other nonpharmacologic therapy, 24% received drug therapy, 4% were referred to a lipidologist, and 30% received no treatment. Fasting lipid profiles were ordered for 57% of these patients. The frequency of therapy was unaffected by patient race or sex, resident level of training or specialty, or presence of two or more cardiac risk factors, although patients with a diagnosis of hypercholesterolemia and patients younger than age 65 were treated significantly more often. Resident action primarily involved evaluation rather than therapy. Efforts to improve the aggressiveness of treatment for hypercholesterolemia by resident physicians are necessary. PMID- 8362894 TI - Induction of cardiac insulin-like growth factor I gene expression in pressure overload hypertrophy. AB - Molecular mechanisms regulating the cardiac hypertrophic response to increased hemodynamic load are understood poorly. Insulin-like growth factor I (IGF I) is a mitogen that is thought to play a key role in pre- and postnatal growth. To investigate a possible role of IGF I in the cardiac response to pressure overload, rats underwent banding of the ascending aorta immediately above the aortic valve using a hemoclip, or a sham procedure. An analysis of left ventricular RNA by Northern hybridization using a 32P-labeled IGF I cDNA revealed four messenger ribonucleic acid transcripts of 7.6, 4.6, 1.7, and 0.9 to 1.2 Kb. Insulin-like growth factor I messenger ribonucleic acid was quantitated by ribonuclease protection assays using a rat exon 3 riboprobe. There was a sustained increase in IGF I mRNA levels that correlated temporally with the development of left ventricular hypertrophy. These results indicate that left ventricular pressure overload is associated with an induction of cardiac IGF I gene expression. Insulin-like growth factor I may play a role in the response to increases in wall stress and likely contribute to cardiac hypertrophy. PMID- 8362895 TI - Heparin does not stimulate coronary-collateral growth in a canine model of progressive coronary-artery narrowing and occlusion. AB - To investigate the possible effect of heparin on coronary-collateral growth, dogs were instrumented chronically with a left circumflex (LCF) flow probe, an ameroid constrictor, a balloon occluder, and left and right atrial and aortic catheters. Collateral blood flow was measured at least weekly or when the coronary artery was occluded. Animals were allocated randomly to a control or treatment group. The latter received a continuous right-atrial infusion of a heparin solution at a rate of 2 to 3 ml/hour and a concentration adjusted daily to increase the activated clotting time to approximately 3 times the pre-drug level. After LCF occlusion, coronary-collateral flow was measured during exercise. There was no difference in time to LCF occlusion in the anticoagulated dogs. Furthermore, neither the rate of collateral development, the magnitude of collateral flow shortly after spontaneous LCF occlusion, nor the degree of collateral vascular reserve during exercise was different in the two groups. Therefore, in this model of coronary obstructive disease, heparin does not accelerate coronary-collateral development. PMID- 8362896 TI - Determination of rebreathing oxygen consumption and derivation of oxygen delivery in intubated mongrel dogs after phlebotomy and isoproterenol infusion. AB - This study attempted to determine the correlation between oxygen consumption (VO2), pulmonary-capillary blood flow (QEPC), and oxygen delivery (DO2) by rebreathing and invasive techniques obtained over a range of hemoglobin concentration and cardiac output. Twenty mongrel dogs were instrumented with central arterial and venous catheters to determine DO2 by thermodilution cardiac output and standard formulas. The animals were administered isoproterenol in doses that increased DO2 and subsequently were serially phlebotomized by 30%, 40%, and 50% to decrease DO2. All animals were studied using a rebreathing technique to determine noninvasively VO2, QEPC, and DO2. Sixteen dogs completed the experimental protocol. A correlation analysis was carried out for VO2, QEPC, and DO2 obtained by the rebreathing and invasive methods. Thermodilution cardiac output increased from 3.91 +/- 1.77 L/min at baseline to 8.19 +/- 2.50 L/min during isoproterenol infusion. Hemoglobin varied from 12.21 +/- 1.26 gm% at baseline to 5.21 +/- 1.36 g% at 50% phlebotomy. Over this range of conditions, significant correlations were obtained between rebreathing VO2 and invasive VO2 (r = 0.80, p < 0.0001), rebreathing QEPC and invasive QEPC (r = 0.79, p < 0.0001), and rebreathing DO2 and invasive DO2 (r = 0.82 p < 0.0001). These data demonstrate that the rebreathing technique can be used to monitor oxygen metabolism over wide ranges of DO2. PMID- 8362897 TI - Analysis of the expression of seven G protein alpha subunit genes in hematopoietic cells. AB - Various heterotrimeric GTP-binding proteins may have important functions in hematopoietic cells. There has been no comprehensive information, however, regarding their expression in various-lineage hematopoietic cells. In this report, the expression level of seven G protein alpha subunits (Gs alpha, Gi1 alpha, Gi2 alpha, Gi3 alpha, Go alpha-1, Go alpha-2, and Gx alpha) in 13 hematopoietic cell lines were analyzed by Northern blot analysis. Gi1 alpha, Go alpha-1, Go alpha-2, and Gx alpha, were expressed in a limited number of cell lines whereas Gs alpha, Gi2 alpha, and Gi3 alpha were expressed ubiquitously in nearly all cell lines tested. Gi1 alpha was expressed selectively in a pre-T cell line, P30/PHK among lymphoid-lineage cell lines and a myeloblastic cell line, KG 1 among myelomonocytoid cell lines. Go alpha-1 was expressed only in a chronic myelocytic-leukemia cell line, K-562, whereas Go alpha-2 was not expressed in any cell lines tested after ordinary exposure of autoradiography (within 4 days). Gx alpha was expressed abundantly in a rat basophilic-leukemia cell line, RBL-2H3, and expressed in K-562. A barely detectable amount of Gx alpha messenger ribonucleic acid (mRNA) was found after a long exposure of autoradiography in several cell lines with megakaryoblastoid phenotype. PMID- 8362898 TI - Creating an objective structured clinical examination for the internal medicine clerkship: pitfalls and benefits. AB - The objective-structured clinical examination (OSCE) is a useful tool in evaluating clinical competence. Traditional clinical-evaluation measures have been criticized as arbitrary and lacking reliability, whereas written exams test primarily cognitive aspects. The OSCE focuses on learner actions rather than abstract knowledge and evaluates in a uniform fashion. A 15-station OSCE was created for an internal medicine junior clerkship, based on predetermined skill and content goals. The exams then were scored by a single, blinded reviewer, again in a predetermined fashion. The OSCE has been studied in terms of reliability, content validity, and construct validity. The exam has become accepted by the department and has guided the continuing curricular development. The OSCE is not designed to measure all the domains of a learner's educational process. However, when used in conjunction with other evaluating mechanisms, it provides an objective outcome measure of the medical education process. PMID- 8362899 TI - Reducing financial barriers enhances the return rate of stool Hemoccult packets. AB - Patient compliance in returning fecal-hemoccult card packets has been studied in recent years but no specific interventions have been shown consistently to improve the return rate. It was wondered whether removing a small financial barrier for indigent patients would positively affect compliance. Therefore, the effect of prepaid postage on the rate of return was studied. Pre-prepared packets containing hemoccult cards with return envelopes were distributed in a randomized fashion to indigent and private insurance patients in outpatient clinics. On half of the return envelopes return postage was applied. The main outcome measure was the rate of return of stamped and unstamped packets stratified between indigent and private insurance patients. The overall rates of return were 117 of 159 (74%) for the stamped packets and 102 of 166 (61%) for unstamped packets (p < 0.02). After stratification, in the indigent patients (n = 177), 73 of 95 (77%) stamped packets were returned compared to 46 of 82 (56%) unstamped packets (p < 0.006). In the private insurance patients (N = 148), 44 of 64 stamped packets (69%) and 52 of 84 unstamped packets (62%) were returned (p > 0.10). Removing even small financial barriers (eg, providing a postage stamp) can enhance compliance for indigent patients. PMID- 8362900 TI - Cytogenetic findings of a child with transcobalamin II deficiency. AB - Transcobalamin II deficiency is a rare, probably autosomal recessive, inborn error of protein metabolism [Hakami et al., 1971]. Several authors have described the morphological characteristics of bone marrow aspirates from patients with this disorder; no reports have detailed the cytogenetic findings [Hitzig et al., 1974; Hakami et al., 1971; Niebrugge et al., 1982]. We report the cytogenetic findings of the bone marrow aspirates from an infant with transcobalamin II deficiency and identify fragile site expression in the hematopoietic cells in this patient. PMID- 8362901 TI - Newly recognized blepharofacioskeletal syndrome. AB - A mother and daughter are described with similar facial and skeletal manifestations. The syndrome consists of blepharophimosis, malar hypoplasia, small thin lips, and long tapering fingers. The facial phenotype changes with age. Autosomal dominant inheritance is suggested. PMID- 8362902 TI - Pericentric inversion of chromosome 6 in a patient with cleidocranial dysplasia. AB - We describe a male patient with a pericentric inversion of chromosome 6 and classic cleidocranial dysplasia (CCD), mild to moderate mental retardation, hearing deficiency, and unusual facial appearance. We conclude that there is a causal relationship between the chromosomal disorder and the CCD. PMID- 8362903 TI - Case of ring chromosome 7: the first report of neuropathological findings. AB - We report on a boy with ring chromosome 7 who had severe mental retardation, growth failure, microcephaly, cleft lip and palate, cafe-au-lait spots, nevus flammeus, and genital abnormalities, and died of pneumonia at age 20 months. On autopsy he had fusion of the anterior cerebral hemispheres, accompanied by agenesis of olfactory bulbs and tracts, closely resembling those found in semilobar holoprosencephaly. In addition, heterotopic Purkinje cell clusters in the cerebellar white matter, absence of pigmentation within the brainstem pigmented neurons, and severe hypomyelination in the whole brain were noted. The patient may represent the most severe manifestation of ring chromosome 7, and this is the first detailed neuropathological report on this subject. PMID- 8362904 TI - Brachydactylous dwarfs of Mseleni. AB - Eight individuals with an unusual dwarfing skeletal dysplasia have been investigated in a remote rural area in Northern Zululand, South Africa. These dwarfed individuals are members of a community numbering some 10,000 persons; approximately 20% have a degenerative arthropathy affecting mainly the major joints of the hips, knees, ankles, and spine. The pathogenesis of the latter disorder, which is known as Mseleni joint disease (MJD), remains obscure. The dwarfed persons have some radiological findings in keeping with MJD, but they are, in addition, of short stature and have marked brachydactyly of their fingers and toes. The pathogenetic relationship between these conditions, if any, is unclear but may have important implications for their causal elucidation. PMID- 8362905 TI - Decrease in thyrocalcitonin-containing cells and analysis of other congenital anomalies in 11 patients with DiGeorge anomaly. AB - Experimental studies have demonstrated that the DiGeorge anomaly is due to cranial neural crest abnormalities. In the present study, the quantitation of thyrocalcitonin immunoreactive cells (C-cells) has been used to evaluate whether cells derived from the cranial neural crest are or are not present in normal proportions in patients with this anomaly. Thyroid sections from 11 such patients and 11 control patients were studied immunohistochemically at autopsy in order to determine the number and distribution of thyrocalcitonin-containing cells. Patients with DiGeorge anomaly showed thymic and parathyroid aplasia/hypoplasia and cardiovascular defects, such as type B interrupted aortic arch, truncus arteriosus and tetralogy of Fallot. Other associated defects were alobar holoprosencephaly and meningocele (previously unreported defects in this anomaly), arhinencephaly, renal cystic dysplasia, ureterohydronephrosis, esophageal atresia with tracheoesophageal fistula, and cleft lip and palate. The volume density of C-cells (1.187%) and the mean number of C-cells per follicle (1.42) was significantly lower in patients with DiGeorge anomaly than in control patients (3.475% and 2.367, respectively). These results indicate a decrease in cells derived from the neural crest in patients with DiGeorge anomaly, and support the hypothesis of a neural crest disturbance as the pathogenetic factor responsible for this anomaly. PMID- 8362906 TI - Unbalanced translocation, t(18;21), detected by fluorescence in situ hybridization (FISH) in a child with 18q- syndrome and a ring chromosome 21. AB - We report on an 8-year-old girl with minor anomalies consistent with 18q- syndrome and mild developmental delay. Initially cytogenetics showed a terminal deletion of chromosome 21 with mosaicism for a small ring chromosome 21 as the only apparent karyotypic abnormality: mos 45,XX,-21/46,XX,+r(21) (48%/52%). Further studies including FISH and DNA analysis demonstrated a de novo unbalanced translocation of chromosomes 18 and 21 with the likely breakpoints in 18q23 and 21q21.1. Most of 21q was translocated to the distal long arm of one chromosome 18, and this derivative 18 appeared to lack 18q23-qter. The small ring chromosome 21 [r(21)], present in only 52% of the patient's blood lymphocytes, did not appear to be associated with the abnormal phenotype since all 13 chromosome 21 markers that were examined in genomic DNA were present in 2 copies, and the phenotype of the patient was consistent with the 18q- syndrome. The karyotype was reinterpreted as mos 45,XX,-18,-21,+der(18) t(18;21) (q23;q21.1)/46,XX,-18, 21,+der(18) t(18;21) (q23;q21.1), +r(21) (p13q21.1) (48%/52%). These results demonstrate the power of FISH in conjunction with DNA analysis for examination of chromosome rearrangements that may be misclassified by traditional cytogenetic studies alone. PMID- 8362907 TI - Prenatal in situ hybridization test for deleted steroid sulfatase gene. AB - X-linked ichthyosis results from steroid sulfatase (STS) deficiency; 90% of affected patients have a complete deletion of the entire 146 kb STS gene on the distal X chromosome short arm (Xp22.3). In these families prenatal diagnosis and carrier testing can be completed in 2 days by hybridizing simultaneously 2 different cosmid probes labeled with fluorescein or Texas red and counterstaining interphase nuclear DNA with DAPI. An STS gene probe labeled with Texas red hybridizes specifically to the steroid sulfatase gene on the X chromosome. A second flanking probe labeled with fluorescein hybridizes to both the normal Y chromosome and normal and STS deleted X chromosomes. In this fashion the interphase nuclei of normal males, affected males, normal females, and carrier females can be distinguished unambiguously. Because normal males and carrier females each show two yellow-green fluorescein spots and one Texas red STS spot, use of this test prenatally requires determining fetal sex independently with repetitive X and Y chromosome-specific probes. This procedure can be used with lymphocytes, direct and cultured chorionic villus cells, direct and cultured amniocytes, and fibroblasts. Similar methods are anticipated to be useful for rapid diagnostic assessment of other aneuploid gene disorders. PMID- 8362908 TI - Mandibulofacial dysostosis: report on two Brazilian families suggesting autosomal recessive inheritance. AB - We report on mandibulofacial dysostosis in 2 brothers born to normal nonconsanguineous parents, and a girl (F = 1/16) born to normal consanguineous parents. Normal clinical, skeletal, audiologic, and cephalometric studies in the parents, as well as the absence of limb anomalies in these children, exclude the autosomal recessive (Nager and Genee-Widemann) mandibulofacial dysostoses. The data of the present patients associated with the few additional reports on mandibulofacial dysostosis recurring in sibs, suggest the possibility of an autosomal recessive Treacher Collins-like mandibulofacial dysostosis. PMID- 8362910 TI - Uniparental disomy revisited: the first twelve years. AB - Uniparental disomy (UPD), the exceptional derivation of a pair of the offspring chromosomes from one parent only, may be compatible with normal or abnormal development and can result from gamete complementation, chromosome loss in trisomy, or duplication in monosomy (with or without residual mosaicism) and somatic recombination. In isodisomy, the uniparental pair is a duplicate of a same chromosome DNA template and causes an increased risk of recessive disorder by reduction to homozygosity. In heterodisomy, the pair remains heterozygous, made up of 2 non-recombinant homologous segments. But both iso- and heterodisomy may also cause disruption of the genomic imprints needed for differential expression of some maternal and paternal genes crucial to growth and development. Pure UPD preserves euploidy and, when harmful, is best regarded as a genomic qualitative imbalance by symmetrical excess and loss of parental homologous contribution affecting zygosity and imprint content. Instances of UPD reported till the spring 1992 are reviewed and their deleterious effects are described as they carried out lethality or morbidity by altering imprinting processes, mimicking deletions, generating recessive disorders, or prompting malignant cellular growth. PMID- 8362909 TI - DNA analysis of cystic fibrosis in Brazil by direct PCR amplification from Guthrie cards. AB - A 3 bp deletion of codon 508 (phenylalanine) of the cystic fibrosis (CF) gene constitutes the mutation of most CF chromosomes. The frequency of this mutation (referred to as delta F508), varies considerably between populations, ranging from 26% of the CF mutations in Turkey to 88% in Denmark. To determine the frequency of the delta F508 mutation in Brazilian Caucasoid CF patients, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards, followed by ethidium bromide staining of gels. Although the overall frequency of the delta F508 mutation was 47% of 380 CF chromosomes from Brazilian Caucasoids born in five different states, significant interstate differences were observed, ranging from a delta F508 frequency of 27% to 53%. While our method could be used to screen patients and their relatives for carrier testing and prenatal diagnosis, the efficacy of screening only for the delta F508 mutation would be low, and would vary from state to state. Screening for a panel of local mutations will be needed to increase the mutation detection rate and optimize genetic counseling. PMID- 8362911 TI - Regional mapping of the gene for familial Mediterranean fever on human chromosome 16p13. AB - Familial Mediterranean fever (FMF) is an autosomal recessively inherited inflammatory disorder characterized by recurrent short episodes of fever, peritonitis, arthritis, and pleuritis. Recently, linkage was demonstrated between FMF and the VNTR probes 3'HVR and 5'HVR of the alpha-globin complex at 16p13.3 (theta = 0.06-0.10, Lodmax = 9.76-14.47) and the insertion/deletion polymorphism detected by the probe CMM65 of D16S84 (theta = 0.04, Lodmax = 9.17). We have now mapped the FMF gene between the two flanking markers D16S283/D16S291 (theta = 0.038) and D16S80 (theta = 0.159). The proximity of the microsatellite markers in D16S283 and D16S291 to the FMF gene allows preclinical diagnosis in most pedigrees with affected individuals. PMID- 8362912 TI - Acalvaria: a unique congenital anomaly. AB - Acalvaria is a rare malformation usually regarded as a postneurulation defect. It consists of absence of the calvarial bones, dura mater and associated muscles in the presence of a normal skull base and normal facial bones. The condition is frequently confused by prenatal ultrasonography with anencephaly or an encephalocele. Whereas the cerebral hemispheres are absent in anencephaly, the cranial contents in acalvaria are generally complete, though some neuropathological abnormality is often present. The presumed pathogenesis of acalvaria is faulty migration of the membranous neurocranium with normal placement of the embryonic ectoderm, resulting in absence of the calvaria but an intact layer of skin over the brain parenchyma. We describe 2 cases of acalvaria, one misdiagnosed ultrasonographically as an occipital encephalocele prenatally. The brain in one fetus demonstrated semilobar holoprosencephaly and micropolygyria, but in the other, was structurally and histologically normal with the exception of hydrocephalus. PMID- 8362913 TI - No evidence for linkage to the type 1 or type 2 neurofibromatosis loci in Noonan syndrome families. AB - A linkage analysis has been performed on 6 two-generation families with classical Noonan syndrome to determine whether the syndrome is linked to neurofibromatosis type 1 on chromosome 17q or to neurofibromatosis type 2 on chromosome 22q. A significantly negative location score was obtained between 10 cM centromeric to and 15 cM telomeric from the neurofibromatosis type 1 locus. A significantly negative lod score was obtained with a marker mapping within the region where neurofibromatosis type 2 is thought to be located. These data indicate that Noonan syndrome is not tightly linked to either neurofibromatosis type 1 or type 2. PMID- 8362914 TI - Brain magnetic resonance imaging findings in the Opitz G/BBB syndrome: extension of the spectrum of midline brain anomalies. AB - We report the brain magnetic resonance imaging findings in 4 patients with the Opitz BBB/G syndrome. The scans were assessed by subjective interpretation and computerized image analysis. Findings noted in 3 of the 4 patients include hypoplasia or agenesis of the corpus callosum (3 patients), cerebellar vermal hypoplasia (2 patients), cortical atrophy and ventriculomegaly (3 patients), macro cisterna magna (3 patients), and a wide cavum septum pellucidum (1 patient). One patient had a normal scan. The demonstration of a wide cavum septum pellucidum extends the spectrum of midline brain anomalies (ventral induction defects) reported in this condition. This study along with other recent reports suggests that midline brain anomalies may be frequent findings in Opitz syndrome. PMID- 8362915 TI - Frontonasal dysplasia in two successive generations. AB - Frontonasal dysplasia is thought to be a sporadic condition limited to the face and head. We describe a family from the Bahamas in which a mother, 2 of her children, and the mother's brother have variable manifestations of frontonasal dysplasia. The mother has extremely mild expression, but her brother and 2 sons are more severely affected. Besides polydactyly no other birth defects were noted in any other relatives. The pedigree is consistent with autosomal or X-linked dominant inheritance. A description of each patient is presented along with a discussion of the genetic counseling issues and review of the literature for other possibly familial cases of frontonasal dysplasia. PMID- 8362916 TI - Moving satellites and unstable chromosome translocations: clinical and cytogenetic implications. AB - We describe 2 families in which acrocentric short arm material moved from one chromosome to another. In case 1, a meiotic event resulted in movement of an unusually large paternal 21p to chromosome 13 in the fetus. In case 2, a mitotic event resulted in fetal mosaicism. The short arm material from a paternal chromosome 15 moved to chromosome 14 in some of the fetal cells. Movement of acrocentric short arm material resulted from breakage and exchange in centromeric areas of repetitive DNA. We suggest the mechanism may be similar to that of previously reported "jumping" translocations. Failure to recognize movement of the short arms of acrocentric chromosomes can result in erroneous interpretation of prenatal cytogenetic results and of other cytogenetic assays dependent on acrocentric short arm polymorphisms. PMID- 8362917 TI - Congenital nonprogressive myopathy with Mobius and Robin sequence--the Carey Fineman-Ziter syndrome: a confirmatory report. AB - Recently, we evaluated a 27-month-old boy with congenital generalized nonspecific myopathy, Mobius sequence, Robin sequence, and failure to thrive. We think the child has the same entity described by Carey, Fineman, and Ziter in 1982 [J Pediatr 101:353-364] and as such represents only the third example of this unusual syndrome. Review of the large number of conditions in which the Robin sequence occurs supports heterogeneity. Our case strengthens the Mobius-Robin association and further defines the Carey-Fineman-Ziter syndrome as a viable entity. It is most likely inherited as an autosomal recessive trait. PMID- 8362918 TI - Is visual field reduction a component manifestation of osteopathia striata with cranial sclerosis? AB - A girl with fully expressed osteopathia striata with cranial sclerosis (OS) was also found to have a contraction of the two visual fields, a sign never previously described in OS syndrome. We suggest that the visual field defect is a component manifestation of OS syndrome, whose pathogenesis is represented by distortion of the optic canal and narrowing of the optic foramina. PMID- 8362919 TI - Unusual fingerprint patterns in Smith-Fineman-Myers syndrome. PMID- 8362920 TI - Unusual complex of congenital malformations. PMID- 8362921 TI - Thrombocytopenia in the Brachmann-de Lange syndrome. PMID- 8362922 TI - On Saraiva and Baraitser and Joubert syndrome: a review. PMID- 8362923 TI - Earliest illustration of an aortic aneurysm by Albrecht von Haller. PMID- 8362924 TI - Axial mesodermal dysplasia spectrum: variable symptoms in affected sibs. PMID- 8362925 TI - Supravalvular aortic stenosis cosegregates with a familial 6; 7 translocation which disrupts the elastin gene. AB - Supravalvular aortic stenosis (SVAS) is an autosomal dominant disorder characterized by abnormalities of development of the great vessels. SVAS is also commonly part of Williams syndrome. Linkage to the elastin gene on chromosome 7q11 has recently been reported in two kindreds with SVAS. Previous reports of patients with 7q11 deletions have noted great vessel abnormalities in some. We report on a family in which SVAS is cosegregating with a balanced reciprocal translocation, t(6:7) (p21.1;q11.23), providing further evidence that SVAS is the result of a mutation of elastin at 7q11.23 region. The propositus of the translocation family has some minor anomalies which occur in Williams syndrome, suggesting that elastin abnormalities may cause some of the abnormalities found in Williams syndrome. PMID- 8362926 TI - On attitudes and appreciation 6 months after predictive DNA testing for Huntington disease in the Dutch program. AB - We have studied the 6-month follow-up attitudes of 63 individuals, after predictive testing for Huntington disease (HD). Reducing uncertainty (81%) and family planning (60%) were the major reasons for taking the test. Twenty-four individuals were diagnosed as having an increased risk (+/- 98%), and 39 a decreased risk (+/- 2%). Among those with an increased risk, denial or minimization of the ultimate impact of the increased risk result was observed. Most of them (84%) rated their current life situation, at the very least, as being good. Twenty-one percent of individuals with an increased risk who originally planned to have a family, decided to refrain from having children. Sixty percent of those with increased risk who still wished to have children, would choose to have prenatal testing. In most individuals with increased risk, the test result did not increase the previously expected control over their own future. Half of the partners of persons with increased risk acknowledged the burden of the future disease. Half had no one in whom they could confide. They showed loyalty to the denial and avoidance reactions of their spouses. Half of the individuals with decreased risk denied the impact of the result, as reflected by absence of relief, and emotional numbness. A third of persons with decreased risk experienced involvement with problems of affected relatives. We found that 20% of all participants were discontented with the support given by their general practitioner, who is normally regarded as being the most significant professional for aftercare. Our findings suggest that the perpetuation PMID- 8362927 TI - What is associated with the fragile X syndrome? AB - In addition to mental retardation (MR), fragile X[fra(X)] syndrome has been associated with a variety of other disorders. Despite earlier reports, it has been shown that MR fra(X) males are at no greater risk for autism than is any MR male. Therefore, studies in which fra(X) has been associated with behavioral, developmental, and psychopathological disabilities were examined to determine whether fra(X) individuals were at an increased risk for these dysfunctions as well. Psychiatric disorders among fra(X) individuals were found not to occur more frequently than in other individuals with cognitive deficits. It was also observed that hyperactivity and attention deficit disorder among MR fra(X) individuals do not occur more frequently than in other MR individuals. Pooled results from studies of cognitive profiles used to characterize fra(X) phenotypes also indicated that there are no consistent patterns in either males or females. Plausible explanations for a variable phenotype include allelic heterogeneity and pleitropy. PMID- 8362928 TI - Associations of disease with genetic markers: deja vu all over again. PMID- 8362929 TI - Candidate genes in psychiatry: an epidemiological perspective. AB - Interest in candidate genes in psychiatry has been revived by the success of that approach in Alzheimer's disease as well as by discouragement over the results to date of searches for linkage. If mutations in candidate genes could be detected directly many of the complexities of searching for them indirectly through linkage could be avoided. As attractive as this approach may sound, mutation searches with candidate genes will introduce a new set of difficulties: the large number and low a priori probability of potential candidate genes virtually guarantees that most positive findings will be false positives. Consequently, if candidate genes are to be systematically studied, procedures need to be established for minimizing and efficiently disconfirming false positive results. PMID- 8362930 TI - Review of the putative association of dopamine D2 receptor and alcoholism: a meta analysis. AB - Eight recent studies have focused on the putative association of the dopamine D2 receptor (DRD2) gene and alcoholism. In this report, these studies are reviewed and the data and findings are examined in a meta-analysis. Four reports find a statistically significant increased risk for alcoholism in subjects carrying the A1 allele and 4 failed to observe a significant increase in risk. Overall, our meta-analysis of the results from all 8 studies supported a statistically significant association between the A1 allele of DRD2 and alcoholism, with an apparent increase in relative risk associated with increased severity of alcoholism. These results must be interpreted cautiously because the A1 allele of DRD2 varies significantly in frequency from one population to another. This variability in the population frequency of the A1 allele could result in an apparent association resulting from unrelated population differences. These findings support the need for carefully designed studies that minimize the ethnic heterogeneity of the subject and control populations. PMID- 8362931 TI - Power to detect linkage with heterogeneity in samples of small nuclear families. AB - Computer simulation methods were used to investigate the power of genetically homogeneous or heterogeneous samples of nuclear families to detect linkage of a rare dominant disease allele to flanking DNA markers (three-point analysis, admixture text). Phase was assumed to be unknown (no grandparents available), and unaffected siblings were not considered. A sample of 95 families with an ill parent and two ill offspring, or 45 families with three ill offspring, demonstrated 90% power to detect a lod score of 3.0 when 50% of families were assumed to be segregating for a disease allele located midway between two DNA markers (PIC = .70) that were .05 M apart. When the proportion of linked families (alpha) = .25, 90% power required 380 and 160 families, respectively. For alpha < .25, samples size requirements become prohibitive. Issues are reviewed concerning the use of the admixture test in the case of more complex disease models. Screening of the genome with adequate sample sizes for low values of alpha is likely to require multiple large collaborative efforts. PMID- 8362932 TI - Practice activities and career satisfaction among fellows of the South Atlantic Association of Obstetricians and Gynecologists. AB - OBJECTIVE: The practice activities and career satisfaction of obstetricians and gynecologists in private practice were compared with those in a teaching faculty setting. STUDY DESIGN: The 475 fellows of the South Atlantic Association of Obstetricians and Gynecologists were surveyed; 314 responses (66.1%) were received. Private practice and teaching faculty respondents were compared regarding practice description, factors influencing choice of practice type, practice activities, and career satisfaction. Data were examined by chi 2 testing and analysis of variance. RESULTS: Patient care involvement was the primary influence in practice choice by 86.0% of private practitioners; interest in teaching was the most important single factor for 58.2% of the teaching faculty. Significantly more teaching faculty than private practitioners had done research work during residency (81.2% vs 53.4%, p < 0.001). There were no differences regarding presentations at medical meetings during residency or publications from work performed during residency. The private practice group recorded more nights on call and more scheduled time off. The teaching faculty showed more publications, continuing medical education credits, hours worked per week, and medical meeting attendance. There were no differences in vacation days, malpractice charges, or expert witness appearances. The group showed no significant differences in their ratings of career satisfaction, but more of the teaching faculty group would elect again to enter obstetrics and gynecology if completing school today (82.4% vs 55.3%, p < 0.001). CONCLUSION: Professional activities of private practice physicians differ from those of teaching faculty physicians. The great majority of both groups are satisfied with their careers. PMID- 8362933 TI - Predicting success of external cephalic version. AB - OBJECTIVE: Many authors have identified prognostic factors for external cephalic version success, but there has not been an attempt to integrate these factors into a simple, quantitative scoring system for predicting version success. Nor have any prognostic factors been prospectively tested. STUDY DESIGN: We examined the clinical characteristics of 108 consecutive breech versions performed between 1984 and 1986. These characteristics were evaluated by stepwise linear regression and discriminate analysis to identify those factors associated with success. Five factors explained the majority of the variability in outcome (parity, placental location, dilation, station, and estimated fetal weight). A model was developed to incorporate the trends identified among these five variables to create a scoring system similar to that of Bishop. This scoring system was then applied to 286 women undergoing external cephalic version since October 1986. RESULTS: There was a positive relationship between a rising version score and the likelihood of successful breech version. No versions were successful with a score < or = 2, and all breech versions were successful with a score of 9 or 10. The results of the version score may have significantly altered physician recommendations in more than one third of cases. CONCLUSION: We believe that this simple, quantifiable scoring system is a refinement in our ability to predict the likelihood of external cephalic version success. PMID- 8362934 TI - A rationale for omitting two-hour postprandial glucose determinations in gestational diabetes. AB - OBJECTIVE: In making decisions regarding initiation of insulin therapy in gestational diabetes, most maternal-fetal obstetricians rely more on elevated fasting glucose values than on elevated 2-hour postprandial levels. We sought to determine whether the latter test is necessary. STUDY DESIGN: From the patients with gestational diabetes mellitus managed over a 17-month period at Grady Memorial Hospital, we retrospectively analyzed data to determine whether normal (< 105 mg/dl) fasting plasma glucose values predict elevated 2-hour postprandial values and whether the latter predict adverse outcome. RESULTS: From 194 patients with gestational diabetes mellitus, 546 paired fasting and 2-hour postprandial glucose values were recorded. Fasting levels were normal in 467 (85%); in those, 2-hour levels were < 120 mg/dl in 83% and < 140 in fully 96%. In 131 women with all fasting plasma glucose values normal, the birth weights and the rates of cesarean delivery, shoulder dystocia, and macrosomia were similar, regardless of whether 2-hour postprandial glucose values were > or = 120. The actual cost of the 546 2-hour postprandial glucose tests was nearly $10,000. CONCLUSION: For metabolic surveillance in gestational diabetes mellitus, the 2-hour postprandial glucose test seems unnecessary, provided fasting plasma glucose values remain normal. PMID- 8362935 TI - A rapid test for abruptio placentae: evaluation of a D-dimer latex agglutination slide test. AB - OBJECTIVE: Our purpose was to evaluate a rapid latex agglutination slide test for D-dimer, a byproduct of clot lysis, in the prediction of abruptio placentae. STUDY DESIGN: Four groups were studied: (1) 15 patients with normal pregnancies at 40 weeks' gestation, (2) 17 participants with preeclamptic pregnancies, (3) 14 patients with preterm labor, and (4) 15 patients with confirmed abruptio placentae. The latex agglutination slide test was performed with positive and negative reference solutions and plasma dilutions of 1:1, 1:2, 1:4, and 1:8. A test was considered positive if, at 2 minutes, agglutination was present at dilutions of > or = 1:2 (> or = 1.0 micrograms/ml fibrin equivalent units). Test results were compared in patient groups with and without abruptio placentae by means of the chi 2 test. RESULTS: The likelihood of a positive D-dimer test result was not significantly different among patients in the non-abruptio placentae groups (p = 0.454). Patients in the abruptio placentae group were significantly more likely to have a positive D-dimer slide test result than those in the non-abruptio placentae groups (p = 0.0001). The D-dimer test conferred sensitivity, specificity, positive predictive value, and negative predictive value of 67%, 93%, 91%, and 48%, respectively. In contrast, other laboratory measures of coagulation (e.g., platelet count, prothrombin time, partial thromboplastin time, and fibrinogen levels) yielded no better than a 20% sensitivity for abruptio placentae. CONCLUSIONS: The D-dimer slide test may be a superior rapid method to improve early diagnosis of abruptio placentae. PMID- 8362936 TI - Myocardial infarction during pregnancy: management and outcome of two pregnancies. AB - OBJECTIVE: Each year in the United States approximately 500,000 women die from ischemic heart disease. However, there are < 100 reported cases of myocardial infarction occurring during pregnancy. The current management of these patients is empiric, with pulmonary artery catheterization during labor being frequently reported. STUDY DESIGN: In the past year we have managed and delivered two such patients, including the first reported case of myocardial infarction with a triplet gestation. RESULTS: Both patients had clinical and laboratory signs of myocardial infarction and underwent coronary angiography. They subsequently had preeclampsia and were prematurely delivered of viable fetuses. One patient had angina pectoris during labor and was successfully treated with sublingual nitroglycerin. Neither patient suffered reinfarction or heart failure. Invasive hemodynamic monitoring was not used, and the mode of delivery was determined solely on obstetric indications. CONCLUSION: In pregnant patients with myocardial infarction, invasive central monitoring is unnecessary in patients with good cardiac function and reserve and the mode of delivery should be based on obstetric indications. PMID- 8362937 TI - Vaginal length and sexual function after colpopexy for complete uterovaginal eversion. AB - OBJECTIVE: Our objective was to evaluate vaginal length and sexual function after colpopexy for complete uterovaginal eversion. STUDY DESIGN: Measurements of postoperative vaginal length were performed on 59 patients having various types of repair for complete uterovaginal eversion. Sexual function was evaluated when possible. Controls were 61 normal premenopausal and postmenopausal patients both with and without a uterus. Anatomic measurements from the introitus to the middle of sacrospinous ligament and to the sacral promontory were obtained from 21 fresh autopsy specimens. RESULTS: Average vaginal length for controls was 9.2 cm in premenopausal patients with a uterus and 8.5 cm for patients without a uterus and averaged 8.5 and 8.2 cm, respectively, for postmenopausal patients with and without a uterus. Vaginal length after posterior culdeplasty was 9.2 cm, 8.2 cm after sacrospinous fixation, and 11.3 cm after sacral colpopexy. CONCLUSION: If maximum vaginal length is the objective, it is best maintained with a sacral colpopexy. PMID- 8362938 TI - Loop electrosurgical excision procedures for cervical dysplasia: experience in a community hospital. AB - OBJECTIVE: The study was undertaken to evaluate the use of the loop electrosurgical excision procedure as an outpatient hospital or surgicenter procedure. STUDY DESIGN: The records of 358 patients treated for cervical intraepithelial neoplasia at a large community hospital over a 1-year period were reviewed. RESULTS: The specimens obtained by loop electrosurgical excision procedure and laser cone excision were comparable in size but smaller than those by means of cold-knife conization. Seventy-two percent of loop electrosurgical excision procedure specimens consisted of two to eight tissue fragments (mean 3.4). In addition, 48% of the loop electrosurgical excision procedure specimens and 38% of laser cones had moderate or severe thermal artifacts. Fragmentation and cautery damage precluded orientation of tissue and evaluation of margins in 19% of the cases. CONCLUSIONS: The advent of the loop electrosurgical excision procedure has shifted the management of cervical intraepithelial neoplasia from the office to the outpatient surgery centers. This negates and, in fact, reverses the advantage of loop electrosurgical excision procedure over other methods in regard to cost and convenience through evaluating and treating a patient with cervical intraepithelial neoplasia in one office visit. Loop electrosurgical excision procedures provide specimens that are inferior compared with cold-knife cones; therefore the role of loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia outside the office appears limited. PMID- 8362939 TI - Diagnostic and treatment results from a southeastern academic center-based premenstrual syndrome clinic: the first year. AB - OBJECTIVES: We attempted to ascertain the following: (1) the yield of a structured workup in a premenstrual syndrome clinic coordinated by a university based gynecology department in the southeast, (2) referral patterns and care provided before consultation, and (3) therapeutic outcomes. STUDY DESIGN: The first 100 women seen prospectively entered a uniform diagnostic and treatment protocol. Data analysis was performed with analysis of variance and confidence interval for a population proportion. RESULTS: Thirty-eight women (95% confidence interval 28% to 48%) had premenstrual syndrome, 24 had premenstrual magnification syndrome (95% confidence interval 16% to 32%), 13 had an affective or other psychiatric disorder (95% confidence interval 6% to 20%). Only 44% of women previously given a diagnosis of premenstrual syndrome were found to have premenstrual syndrome. Overall, 84% of women with premenstrual syndrome and premenstrual magnification syndrome responded to treatment. CONCLUSIONS: Too many women are still given the diagnosis of premenstrual syndrome without appropriate prospective documentation. Premenstrual magnification represents an important diagnostic category. Therapeutic responses to present treatments are encouraging. PMID- 8362940 TI - Paraaortic lymph node sampling by means of an extraperitoneal approach with a supraumbilical transverse "sunrise" incision. AB - OBJECTIVES: Extraperitoneal approaches to removal of lymph nodes for staging in cervical cancer patients are numerous, and each has disadvantages. We developed a supraumbilical transverse incision to initiate irradiation within days of cervical cancer staging. STUDY DESIGN: Twenty patients with advanced stage IIB or IIIB cervical cancer underwent surgical staging with a supraumbilical incision during the time period Jan. 1, 1988, to Aug. 1, 1992. The incisions were made 6 cm above the umbilicus and carried laterally in a caudad manner to the iliac crests. All nodes were removed in an extraperitoneal fashion. RESULTS: In the 20 patients who were operated on, the mean number of nodes removed was 9.8. Estimated blood loss ranged from 50 to 300 ml. The procedure time ranged from 50 to 150 minutes. All patients but two had irradiation initiated within 2 weeks of the procedure. Complications included an identified and repaired ureteral injury, a prolonged ileus, and a small bowel obstruction. CONCLUSIONS: An extraperitoneal approach with the "sunrise" incision allows irradiation to begin within days of surgery. The operating time is relatively short. The incision can be extended caudally and extraperitoneally if needed for removal of bulky pelvic nodes. PMID- 8362941 TI - Incidence of perceived and actual face shield contamination during vaginal and cesarean delivery. AB - OBJECTIVE: The purpose of this study was to determine the rate of potential contamination or splashes to the face of obstetricians during vaginal and cesarean delivery. STUDY DESIGN: Clear plastic face shields were worn during 50 consecutive vaginal and 50 consecutive cesarean deliveries. The face shields were then analyzed for evidence of contamination, and rates of contamination were compared. RESULTS: The contamination rate of the face shields was 50% during cesarean deliveries and 32% during vaginal deliveries. Ninety-two percent of the contaminated face shields were undetected by physicians at the time of cesarean delivery and 50% were undetected at the time of the vaginal delivery. CONCLUSIONS: Obstetricians commonly receive blood or amniotic fluid splashes to the face during deliveries and should wear protective eyeglasses or face shields during all deliveries to minimize the risk of exposure to potentially infectious blood and body fluids. PMID- 8362942 TI - Control of postpartum hemorrhage with uterine packing. AB - OBJECTIVE: A historic survey of the literature and nine recent examples of uterine packing for control of postpartum hemorrhage are presented. Once a frequently practiced art, intracavitary packing for the control of uterine postpartum bleeding became a lost skill to most physicians after the 1950s. Objections to the practice are presented through a review of the literature. STUDY DESIGN: The technique of uterine packing is critical in the control of hemorrhage and is briefly reviewed. RESULTS AND CONCLUSION: Whether used early or late in patient management, uterine packing for the control of postpartum hemorrhage is a safe, quick, and effective procedure. PMID- 8362943 TI - Treatment of male infertility and idiopathic failure to fertilize in vitro with under zona insemination and direct egg injection. AB - OBJECTIVE: Failure to fertilize eggs in vitro may be countered by micromanipulation of gametes to place selected spermatozoa underneath the zona pellucida of the egg or directly into the egg, thereby improving chances of fertilization and production of viable embryos. Analysis of our clinical data for assisted fertilization was undertaken to assess those factors of relevance in this therapy, and a description of our procedures are given. STUDY DESIGN: Retrospective analysis of 85 cycles (73 couples) of in vitro fertilization and embryo transfer performed at a private infertility clinic, in which micromanipulation for assisted fertilization was used to overcome either severe male factor infertility or idiopathic failure to fertilize, was performed. RESULTS: In 60 cycles where only embryos from under zona insemination were available for uterine transfer, 15 singleton and two twin pregnancies occurred (28.3% viable pregnancy rate per transfer, 14.1% embryonic implantation). In 14 of these cycles embryos arose only after repeated under zona insemination adding more spermatozoa; this accounted for four of the singleton and one of the twin pregnancies (38.5% pregnancy rate, 22.2% embryonic implantation). No embryos arose from partial zona dissection performed in five cycles on sibling eggs. However, in 16 cycles conventional insemination yielded fertilization in six cycles, and mixed transfer of these embryos and sibling embryos from under zona insemination gave rise to one pregnancy from four transfers (pregnancy rate 25%, embryonic implantation 7.1%). Likewise, in nine cycles donor spermatozoa yielded fertilization in eight cycles, and mixed transfer with sibling embryos fertilized by under zona insemination with partner's spermatozoa gave rise to two pregnancies from five transfers (pregnancy rate 40%, embryonic implantation 15.8%). Fertilization and pregnancy rates did not differ whether couples suffered either from male factor infertility or from previous idiopathic fertilization failure. Direct egg injection of a single spermatozoon into 105 eggs gave an 88.6% egg survival and 32.3% fertilization. Mixed transfers with sibling embryos from conventional and under zona insemination yielded one triplet, one twin, and three singleton pregnancies. CONCLUSIONS: Overall, a 24.7% (21/85) viable pregnancy rate per cycle initiated occurred when only embryos from assisted fertilization were available. This strongly indicates that assisted fertilization made a real contribution in cases where either insufficient spermatozoa were available for conventional insemination or in cases where previous fertilization failure had arisen. The wide range of seminal parameters were found to be unhelpful in defining chances of success with assisted fertilization. PMID- 8362944 TI - Intraamniotic 15(s)-15-methyl prostaglandin F2 alpha and termination of middle and late second-trimester pregnancy for genetic indications: a contemporary approach. AB - OBJECTIVE: Our purpose was to determine whether intraamniotic 15(s)-15-methyl prostaglandin F2 alpha could serve effectively and safely as a surrogate for natural prostaglandin F2 alpha when used to effect middle and late second trimester pregnancy termination for genetic indications. Further, we sought to compare efficacy and side effects with those found when intravaginal prostaglandin E2 is used. STUDY DESIGN: A total of 62 patients received intraamniotic 15(s)-15-methyl prostaglandin F2 alpha and urea, and intracervical laminaria. Case patients at < or = 20 weeks' gestation (n = 32) were compared with case patients at > 20 weeks (n = 30) and with a matched group (n = 64; 1:2 ratio) of control patients in whom cervical laminaria and intraamniotic urea were used with prostaglandin E2 vaginal suppositories. RESULTS: The mean induction-to abortion interval among the case patients (gestational age 16 to 27 weeks) was 13 hours 11 minutes; 60 of 62 (97%) were delivered within 24 hours. There was a statistically significant negative correlation between the induction-to-abortion interval and gestational age (p = 0.04). When patients at < or = 20 weeks and those at > 20 weeks were compared, few differences were noted. The mean induction to-abortion interval for case patients at < or = 20 weeks was 13 hours 54 minutes versus 19 hours 34 minutes for control patients (p = 0.001). One of 32 (3%) case patients remained undelivered beyond 24 hours compared with 17 of 64 (27%) control patients (p < 0.01). Immediate and delayed complications were uncommon in either group. CONCLUSION: Our study demonstrates that 15(s)-15-methyl prostaglandin F2 alpha can serve safely as a surrogate for prostaglandin F2 alpha when used in combination with urea and laminaria for termination of pregnancy. This technique appears safe for use through 27 weeks' gestation; further investigation is encouraged. PMID- 8362945 TI - Atypical pelvic inflammatory disease: can we identify clinical predictors? AB - OBJECTIVE: We used data from a large multicenter case-control study of tubal infertility to analyze further the relationship among demographic variables, behavioral measures, history of previous sexually transmitted diseases, and past contraceptive practices, for women with and without a history of pelvic inflammatory disease. STUDY DESIGN: We identified 283 white women with tubal infertility who requested care at seven participating institutions. Of these women, 238 (84%) did not have a history of pelvic inflammatory disease ("atypical pelvic inflammatory disease") whereas 45 reported a history of pelvic inflammatory disease ("overt pelvic inflammatory disease"). We compared these groups with 1629 white women without a history of either infertility or pelvic inflammatory disease who were delivered of their first live-born child at the same institutions as the infertile cases. RESULTS: Women with atypical pelvic inflammatory disease were demographically more like fertile control subjects and had behavioral characteristics midway between those of the overt pelvic inflammatory disease group and the fertile group. Both oral contraceptive and diaphragm use protected against tubal infertility for women with either atypical or overt pelvic inflammatory disease. Atypical pelvic inflammatory disease was related to a history of Trichomonas infection but not to a reported history of gonorrhea, genital herpes, or other vaginitis. CONCLUSION: Atypical pelvic inflammatory disease is probably more common than its symptomatic counterpart. Whereas this condition is associated with some characteristics of a sexually transmitted infection, clinical predictors remain elusive. PMID- 8362946 TI - Fetal heart circumference as a predictor of menstrual age in fetuses affected by disturbances in growth. AB - OBJECTIVE: The purpose of this study was twofold: (1) to evaluate the relationship between fetal heart circumference and gestational age and (2) to determine the effect, if any, of disturbances in fetal growth on heart circumference. STUDY DESIGN: Heart circumference was measured in 262 women with normal gestations (control group) and in two study groups consisting of 52 large for-gestational age 32 small-for-gestational age fetuses. Standardized, gestational age-adjusted values in the two study groups were compared with normative data provided by the control group. RESULTS: There was a close correlation (R2 = 0.94) between heart circumference and gestational age in normally growing fetuses. Disturbances of fetal growth (i.e., macrosomia and growth retardation) were found to have an inconsistent effect on heart circumference. CONCLUSION: Heart circumference cannot be used as an independent parameter for gestational age evaluation in fetuses with disturbances of growth. PMID- 8362947 TI - Multicenter randomized, controlled trial of a preterm birth prevention program. Collaborative Group on Preterm Birth Prevention. AB - OBJECTIVE: The results of a randomized, controlled trial of a preterm birth prevention program at five centers with primarily low-income populations are presented. STUDY DESIGN: Pregnant women at high risk for preterm labor were independently randomized into intervention and control groups at each of five centers (2395 women). Specially trained staff instructed women in the intervention group to recognize early signs of preterm labor and to notify the staff should any sign of preterm labor occur, and women came in weekly for pelvic examinations after 20 to 24 weeks' gestation. Because the intervention had very different and contrary effects on preterm birth rates across these sites, the analysis focused on patient risks and on measures of the process of care as possible explanations for the differences in outcomes. RESULTS: The observed spontaneous preterm birth rates, when averaged for all sites, were not lower in the intervention group than in the control groups (16.1% vs 15.4% for < 37 completed weeks' gestation, 11.9% vs 10.9% for < 36 completed weeks). There was substantial heterogeneity of program effects between centers (p < 0.01 for homogeneity test statistic). The differences in intervention effects between centers were explainable only in part by patient risk characteristics (p < 0.10 for homogeneity test statistic). The only intermediate measure of the process of care that tended to differentiate among sites with positive intervention effects was the rate of hospital admission for preterm labor. Sites with elevated admission rates in the intervention group versus the control group tended to have negative intervention effects on outcomes. CONCLUSION: Because the preterm birth prevention program did not show a reliable benefit and because the reasons for varied outcomes are not understood, the use of the program cannot be recommended for predominantly low-income populations. PMID- 8362948 TI - Lyme disease and pregnancy outcome: a prospective study of two thousand prenatal patients. AB - OBJECTIVE: The purpose of the study was to determine if prenatal exposure to Lyme disease was associated with an increased risk of adverse pregnancy outcome. STUDY DESIGN: Approximately 2000 Westchester County, New York, women completed questionnaires and had sera tested for antibody to Borrelia burgdorferi at their first prenatal visit and at delivery. Fetal death, birth weight, length of gestation at delivery, and congenital malformations were examined in relation to maternal Lyme disease exposure before and during pregnancy. RESULTS: Maternal Lyme disease or an increased risk of exposure to Lyme disease was not associated with fetal death, decreased birth weight, or length of gestation at delivery. Tick bites or Lyme disease around the time of conception was not associated with congenital malformations. Tick bites within 3 years preceding conception were significantly associated with congenital malformations, but this could have reflected reporting differences between exposed and unexposed women. CONCLUSIONS: Maternal exposure to Lyme disease before conception or during pregnancy is not associated with fetal death, prematurity, or congenital malformations taken as a whole. We have not ruled out the possibility that exposure to Lyme disease as defined by maternal history increases the risk of specific malformations or has an effect if it is not treated. We have insufficient numbers of women who were seropositive at their first prenatal visit to determine if this subgroup of exposed women are at a moderately increased risk of having a child with a congenital abnormality. The low frequency of seroconversion at delivery in this endemic area suggests that preventive measures are being taken by obstetricians and patients. PMID- 8362949 TI - Routine testing for Chlamydia trachomatis on Curacao, Netherlands Antilles. AB - OBJECTIVE: Although genital Chlamydia trachomatis infection is most often asymptomatic, early treatment may prevent serious complications. For screening or routine testing to be cost effective, the prevalence of the infection must not be too low. STUDY DESIGN: On Curacao, Netherlands Antilles, the prevalence of chlamydial infection in 205 asymptomatic women of reproductive age, who were seen by a general practitioner or gynecologist for a gynecologic examination was measured. RESULTS: The overall prevalence was found to be 5.4% (95% confidence interval 2.7% to 9.4%) with the enzyme-linked immunosorbent assay method. Of all possible predictors of a chlamydial infection, only young age (< 25 years, prevalence 10.3%) seemed to be indicative of such an infection. CONCLUSION: Routine testing for Chlamydia trachomatis in sexually active women on Curacao and on other Caribbean islands is indicated for women < 25 years old. PMID- 8362950 TI - Erythrocytes in fetuses with abnormal umbilical artery flow velocity waveforms. AB - OBJECTIVE: Our purpose was to measure erythrocyte indexes in fetuses with two grades of Doppler-defined umbilical placental insufficiency. STUDY DESIGN: A prospective study comprising 110 infants categorized into control, moderate, and severe groups by umbilical artery waveform studies was undertaken at the University of Sydney at Westmead Hospital. Fetal erythrocyte indexes were measured in umbilical venous blood. Multivariate analyses of variance with post hoc Bonferroni t tests were used in the statistical analysis. RESULTS: The erythrocyte count, hematocrit, and hemoglobin concentration were all significantly higher (p < 0.001) in the two placental insufficiency groups than in the controls. Both placental insufficiency groups were affected to the same extent. CONCLUSIONS: Differences exist in the erythrocyte populations of fetuses with Doppler-defined placental insufficiency compared with controls. Importantly, these differences occur in more than just the most severe cases. These changes may represent a compensatory response to the placental vascular lesion detected by abnormal umbilical artery waveforms. PMID- 8362951 TI - Early prenatal ultrasonographic diagnosis of osteogenesis imperfecta: a case report. AB - A case of lethal osteogenesis imperfecta detected at 14 weeks' gestation by transvaginal ultrasonography is described. The prenatal diagnosis of limb shortening deformities caused by fractures and their repair is discussed. PMID- 8362952 TI - Ovarian cortex surrounding benign neoplasms: a histologic study. AB - OBJECTIVE: Our purpose was to assess the functional morphologic features of the ovarian cortex surrounding benign cysts. STUDY DESIGN: Fifty-four specimens (13 mature teratomas, nine benign cystadenomas, and 32 endometriomas) were obtained from the area of maximum distention of the ovarian cortex overlying benign cysts from 48 patients. The type and number of follicles were scored on a semiquantitative scale (0 to 4). Alterations of the cortical stroma that were related to the primary tumor were investigated. The vascular network was assessed by means of monoclonal antibodies directed against endothelial cells (anti-VW, QBEND/10) and scored on a scale from 0 to 2. The chi 2 and Mann-Whitney U test were used for statistical analysis. RESULTS: Morphologic patterns similar to those of the normal ovarian cortex were observed in the cortical tissue surrounding mature teratomas, benign cystomas, and endometriomas in 92%, 77%, and 19% (p < 0.01) of specimens, respectively, and a regular vascular network was observed in 84%, 78%, and 22% (p < 0.01). Although microscopic endometriosis was observed surrounding the endometrioma in the stroma of 82% of specimens, stromal alterations related to the ovarian tumor were absent in the cortex surrounding mature teratomas and cystadenomas. CONCLUSIONS: The study shows that the ovarian cortex, which is stretched and thinned by the growth of a benign tumor, is not morphologically altered in the presence of teratomas or benign cystadenomas. Endometriomas are associated with microscopic stromal implants and reduced follicular number and activity. PMID- 8362953 TI - Pregnancy in patients with cyclic neutropenia. AB - Cyclic neutropenia is characterized by periodic episodes of neutropenia that are often associated with infectious complications. A patient with cyclic neutropenia experienced two pregnancies with an amelioration of her infectious complications and an increase in neutrophil count. Cyclic neutropenia may follow a benign course during pregnancy. PMID- 8362954 TI - Moyamoya disease in pregnancy: a case report. AB - Moyamoya disease is a rare condition characterized by narrowing and occlusion of the internal carotid arteries. The disease usually presents as alteration of consciousness caused by intracranial hemorrhage. We describe a case of moyamoya disease presenting as seizures in a pregnant patient. The characteristic angiographic appearances and plan of management are described. PMID- 8362955 TI - Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy. AB - OBJECTIVE: Our purpose was to investigate the cytokines, tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy and labor. STUDY DESIGN: Bioassays were used to measure these factors in extraembryonic coelomic fluid, amniotic fluid, placenta, and maternal and cord serum. RESULTS: Little or no tumor necrosis factor, interleukin-1, or interleukin-6 was found in coelomic fluid or amniotic fluid in the first trimester. Interleukin-6 appeared in second trimester amniotic fluid. At term tumor necrosis factor was present (median 17 pg/ml) and increased with the onset of labor (median 58 pg/ml), as did interleukin-1 (median 188 to 680 pg/ml) and interleukin-6 (median 399 to 4800 pg/ml). Maternal serum interleukin-6 increased during pregnancy with a further increment with the onset of labor. Cord interleukin-6 also increased with labor but at a lower level. CONCLUSION: The cytokines tumor necrosis factor, interleukin-1, and interleukin-6 may play a role in the onset of normal labor. PMID- 8362956 TI - Ultrasonographic measurement of cheek-to-cheek diameter in fetal growth disturbances. AB - OBJECTIVE: Our purpose was to assess the value of the cheek-to-cheek diameter and the cheek-to-cheek diameter/biparietal diameter ratio in the ultrasonographic detection of abnormal fetal growth. STUDY DESIGN: The cheek-to-cheek diameter and cheek-to-cheek diameter/biparietal diameter ratio were examined in 21 small-for gestational-age (< 10th percentile for estimated weight) and 87 large-for gestational-age (> 90th percentile) fetuses. Statistical analysis consisted of Student's t test comparison between means and analysis of covariance for comparison of regression lines slope between these 108 fetuses and previously published nomograms of appropriate-for-gestational-age fetuses. RESULTS: The mean cheek-to-cheek diameters in small-for-gestational-age fetuses were significantly smaller than in appropriate-for-gestational-age fetuses (p < 0.0001). In large for-gestational-age fetuses the mean cheek-to-cheek diameters were significantly larger (p < 0.005). Although large-for-gestational-age fetuses of diabetic mothers exhibited higher cheek-to-cheek diameter/biparietal diameter ratios than did appropriate-for-gestational-age fetuses (p < 0.0001), in fetuses of nondiabetic mothers this ratio was only minimally larger (p < 0.05). CONCLUSION: The cheek-to-cheek diameter and cheek-to-cheek diameter/biparietal diameter ratio are innovative ultrasonographic parameters for detecting abnormal fetal growth. Furthermore, the cheek-to-cheek diameter/biparietal diameter ratio permits insight into the possible underlying pathophysiologic mechanisms of fetal macrosomia. PMID- 8362957 TI - Embryopathic effects of the oral hypoglycemic agent chlorpropamide in cultured mouse embryos. AB - OBJECTIVES: The oral hypoglycemic agent chlorpropamide was evaluated for embryopathic effects in the mouse embryo model. STUDY DESIGN: Mouse embryos (n = 10 to 31 per group) were exposed in whole embryo culture to serum from chlorpropamide-treated rats or chlorpropamide-supplemented control rat serum. Hypoglycemic serum from chlorpropamide-treated rats was supplemented with glucose to control for effects of hypoglycemia. Differences in malformation rates were evaluated by Fisher's exact test and numerical differences by analysis of variance. RESULTS: Mouse embryos were malformed by > or = 24 micrograms/ml of chlorpropamide, embryonic protein content and somites were decreased by > or = 130 micrograms/ml of chlorpropamide, and visceral yolk sac protein was reduced by > 500 micrograms/ml of chlorpropamide. Similar development occurred in serum from chlorpropamide-treated rats and chlorpropamide-supplemented control serum, and growth was not improved by adding glucose. CONCLUSIONS: Chlorpropamide produces malformations and growth retardation in mouse embryos in vitro at concentrations overlapping therapeutic levels in humans. Chlorpropamide-induced defects are not mediated by hypoglycemia or by products of chlorpropamide metabolism. PMID- 8362958 TI - Plasma oxytocin and nocturnal uterine activity: maternal but not fetal concentrations increase progressively during late pregnancy and delivery in rhesus monkeys. AB - OBJECTIVE: The purpose of the study was to determine whether rising maternal or fetal plasma oxytocin concentrations could be responsible for the increasing levels of nocturnal uterine activity on the nights preceding delivery. STUDY DESIGN: Chronically catheterized pregnant rhesus monkeys were exposed to a 16 hour light, 8-hour dark photoperiod (dark 11 PM to 7 AM). Uterine activity and maternal arterial plasma oxytocin concentrations were measured concurrently at weekly intervals in late gestation, on the night preceding term delivery (158 to 167 days, n = 4), and during delivery (149 to 170 days, n = 6). Fetal carotid arterial plasma oxytocin levels were measured during episodes of nocturnal uterine activity in six animals. The effect of oxytocin infusions into the fetus (30 to 480 ng/kg/hr) on uterine activity and on maternal and fetal plasma oxytocin levels was also determined (n = 3). RESULTS: Maximal nocturnal oxytocin concentrations in the maternal plasma rose progressively during late gestation from 9.9 +/- 3.5 pg/ml at 130 to 139 days to 28.7 +/- 9.8 pg/ml on the night preceding term delivery (p < 0.005); a significant increase in nocturnal uterine activity accompanied this rise (p < 0.001). Maternal oxytocin concentrations were elevated during labor and increased further at delivery (62.5 +/- 5.5 pg/ml, p < 0.05). There was no increase in fetal plasma oxytocin during nocturnal uterine activity (3.1 +/- 0.2 pg/ml) or during labor. Fetal oxytocin infusions raised fetal plasma oxytocin concentrations sixtyfold but had no effect on maternal plasma oxytocin concentrations or on uterine activity. CONCLUSIONS: Elevated maternal plasma oxytocin concentrations are responsible, at least in part, for the increasing magnitude of nocturnal uterine activity episodes as term approaches and for the elevated uterine activity before delivery at night. Fetal plasma oxytocin does not contribute to nocturnal uterine activity or to maternal plasma oxytocin concentrations. PMID- 8362959 TI - Transfer of maternally administered magnesium sulfate into the fetal compartment of the rat: assessment of amniotic fluid, blood, and brain concentrations. AB - OBJECTIVE: Our purpose was to determine whether parenteral magnesium sulfate crosses the rat placenta and enters the fetal brain. STUDY DESIGN: Twenty-eight pregnant female Long-Evans rats were divided into four groups, seven animals in each group. These groups included the following: single saline solution injection group evaluated after 20 minutes (control), single magnesium sulfate injection (270 mg/kg) evaluated after 20 minutes, and prolonged (2 and 4 hours) serum magnesium elevation (270 mg/kg loading and then 27 mg/kg every 20 minutes for maintenance). Each animal was killed, and maternal and fetal sera, amniotic fluid, and specific brain areas were analyzed for levels of magnesium. Statistical analysis included analysis of variance, multiple comparison procedure, and linear regression analysis. RESULTS: All three regimens of maternal subcutaneous magnesium sulfate resulted in significantly elevated maternal serum magnesium concentrations (p < 0.01). Fetal blood magnesium concentration rose from 3.9 +/- 0.3 to 4.9 +/- 0.1 mg/dl after 2 hours of continuous injections (p < 0.05), and to 5.3 +/- 0.0 mg/dl after 4 hours (p < 0.01). Amniotic fluid magnesium concentrations rose from 4.2 +/- 0.2 to 5.1 +/- 0.1 mg/dl after 4 hours (p < 0.05). Maternal blood magnesium concentrations were significantly correlated with amniotic fluid concentrations (r = 0.59, p < 0.01). Four hours of maternal magnesium sulfate treatment resulted in a 25% increase in magnesium concentrations in the fetal forebrain (38.3 +/- 2.3 to 47.9 +/- 3.5 mg/dl/gm, p < 0.05). No significant changes in magnesium concentrations were detected in hindbrain. CONCLUSION: Magnesium sulfate injected subcutaneously into rats crosses the placenta within 2 hours of sustained magnesium levels, enter the fetal blood-brain barrier, and concentrates in the forebrain. PMID- 8362960 TI - Perihepatic adhesions and pelvic infection. PMID- 8362961 TI - Ultrasonography in hereditary angioneurotic edema during pregnancy. PMID- 8362962 TI - The smaller-than-expected first-trimester fetus. PMID- 8362963 TI - Chlamydia and recurrent pregnancy loss. PMID- 8362964 TI - Amniotic fluid volume determination. PMID- 8362965 TI - Calculation of blood loss at delivery. PMID- 8362966 TI - "The effect of presentation and mode of delivery on neonatal outcome in the second twin"--is this study biased? PMID- 8362967 TI - Expression and localization of tumor necrosis factor-alpha and its mRNA in idiopathic pulmonary fibrosis. AB - The expression of tumor necrosis factor alpha and its mRNA was investigated in surgical biopsies from idiopathic pulmonary fibrosis by immunohistochemistry, in situ hybridization, and Northern blotting. Normal areas of lungs resected for cancer were used as controls. Tumor necrosis factor alpha mRNA levels were higher in idiopathic pulmonary fibrosis than in normal lungs as determined by Northern blots. In normal lungs, tumor necrosis factor alpha and its mRNA were identified in alveolar and interstitial macrophages. In fibrotic lungs, tumor necrosis factor alpha was detected in macrophages and, to a greater extent, in epithelial cells (presumably type II cells) lining the thickened septae. Tumor necrosis factor alpha mRNA was found only in some interstitial cells and some of the cells lining the alveolar septae. An elevated concentration of tumor necrosis factor = alpha, particularly within the alveolar epithelium, might contribute to the alveolar damage and proliferation of interstitial cells in idiopathic pulmonary fibrosis. PMID- 8362968 TI - A putative marker for human melanoma. A monoclonal antibody derived from the melanoma gene in the Xiphophorus melanoma model. AB - A MoAb was raised against a peptide corresponding to an exposed domain of the putative tyrosine kinase receptor protein encoded by Xmrk, a gene involved in melanoma formation and/or progression in the Xiphophorus fish melanoma model. The antibody reacts specifically with cells from human melanocytic lesions, ie, common acquired nevi, primary and metastatic melanoma biopsies. No reactivity with other cells, including normal melanocytes, was observed in the biopsies or with cells in biopsies from normal tissue (skin, liver, lung, spleen) and from other malignancies including those of neuroectodermal origin. The reactivity was very weak and variable in metastatic melanomas but very strong and characteristic of a receptor-type antigen in primary melanomas, a stage in melanoma progression in which cells have acquired metastasizing potential. It is suggested that the antigen recognized may be involved in growth promotion and represents the human equivalent of the fish melanoma gene product. PMID- 8362969 TI - Interstitial collagenase gene expression in colonic neoplasia. AB - Tumor invasion and metastasis are complex phenomena believed to be facilitated by the disruption of collagen and elastin fibers in the extracellular matrix. Interstitial collagenase gene expression was studied in colonic adenocarcinoma and adenoma using in situ hybridization. The data indicated that three cell types within the tumor stroma expressed collagenase transcripts; they were eosinophils, fibroblasts, and vascular endothelium. In all 12 adenocarcinomas, a high to moderate level of expression was seen in 1 to 5% of eosinophils and in occasional fibroblasts, whereas these cell types in non-neoplastic mucosa adjacent to tumor showed no detectable expression. Two adenocarcinomas showed expression in hyperplastic endothelium in vascularized granulation tissue. Two out of three adenomas showed expression in eosinophils and fibroblasts at a reduced level. Tissue inhibitor of metalloproteinase-1 gene expression was, however, negligible in all tissue examined. These results suggest that interstitial collagenase gene activation in the tumor stroma, especially eosinophils, may have an important role in tumor invasion and metastasis. PMID- 8362970 TI - LFA-1 expression on exocrine glands as a potential novel marker of malignant disease. AB - The lymphocyte function associated antigen 1 has been found only on leukocytes and lymphoid tissues; however, the expression of lymphocyte function associated antigen 1 on nonhematopoietic cells has not been reported previously. In this study, immunohistochemical expression of lymphocyte function associated antigen 1 was examined on various tissues from 35 patients with malignant diseases and 36 patients with benign diseases including benign tumors. The expression of lymphocyte function associated antigen 1 was found on various exocrine tissues (eg, gastric glands, bronchial epithelium, alveolar epithelium, duodenal glands, bile ducts, pancreatic acini, and salivary glands) uninvolved by tumor in patients with malignant diseases. Localization of lymphocyte function associated antigen 1 was limited to the exocrine glands and differed from tissue infiltrating leukocytes. The expression of lymphocyte function associated antigen 1 on exocrine tissues was confirmed in all 35 cases of malignant diseases that were examined. These included a wide spectrum of carcinomas and hematopoietic tumors. In contrast, none of the 36 cases with benign diseases examined expressed lymphocyte function associated antigen 1 on their exocrine glands. These results indicate a strong correlation between lymphocyte function associated antigen 1 expression on exocrine glands and malignant disease. The expression of lymphocyte function associated antigen 1 on nonhematopoietic cells was further confirmed in nonhematopoietic cell lines. Two of 19 nonhematopoietic cell lines (MKN45 and PANC-1; exocrine gland cell lines) examined expressed lymphocyte function associated antigen 1 on both cell surface and cytoplasm. These results suggested that immunohistochemically defined lymphocyte function associated antigen 1 molecules on nontumorous exocrine gland cells are a potential marker for the presence of malignant diseases. PMID- 8362971 TI - Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation. AB - In a series of 22 pancreatic acinar cell carcinomas, including two acinar cystadenocarcinomas, cellular differentiation was analyzed by immunocytochemistry and electron microscopy. In addition, overexpression of p53 protein and Ki-ras codon 12 mutation was studied. Four of the 20 noncystic acinar cell carcinomas showed a pure acinar pattern, nine an acinar-solid, and seven a solid pattern. All tumors stained for at least one of the following pancreatic acinar markers: trypsin (21 of 22), lipase (19 of 22), chymotrypsin (13 of 22), phospholipase A2 (nine of 22), and pancreatic stone protein (19 of 22). One-third of the tumors expressed neuroendocrine markers (synaptophysin, eight of 22; chromogranin A, six of 21) and duct cell markers (CA19.9, nine of 21; B72.3, six of 21). Cellular coexpression of trypsin and synaptophysin was demonstrated in one tumor. Electron microscopy revealed zymogen granules (nine of nine). In only one of 16 tumors a Ki-ras mutation at codon 12 was found, whereas in none of 19 tumors could overexpression of p53 protein be demonstrated. The results suggest that acinar cell carcinomas show obvious capacity to differentiate into several directions, but nevertheless constitute an entity different from ductal adenocarcinomas or endocrine tumors. PMID- 8362972 TI - Alterations of thymus cortical epithelium and interdigitating dendritic cells but no increase of thymocyte cell death in the early course of simian immunodeficiency virus infection. AB - The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low (< 1 in 10(4) T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate and flow cytometry showed a reduction of the immature CD4+/CD8+ double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, and finally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis. PMID- 8362973 TI - Expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in the normal and cirrhotic human liver. AB - We compared the expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in normal human liver, in which the endothelial lining of hepatic sinusoids is discontinuous and devoid of basement membrane, and in cirrhosis, during which sinusoids might undergo a process of capillarization and acquire a continuous lining and a typical basement membrane. In normal liver, sinusoidal endothelial cells displayed a very restricted repertory of cell adhesion molecules: the intercellular adhesion molecules PECAM-1 and CD34 were undetectable and only two integrins, alpha 1 beta 1 and alpha 5 beta 1, were present, whereas the laminin receptors alpha 6 beta 1 and alpha 2 beta 1 were undetectable and the beta 3 integrins were faintly expressed. In capillarized sinusoids, sinusoidal endothelial cells displayed striking changes in their repertory of cell-adhesion molecules, including the expression of PECAM-1 protein and messenger RNAs and the induction of the laminin receptors alpha 6 beta 1 and alpha 2 beta 1. Such changes co-localized with subendothelial laminin deposits. In conclusion, normal sinusoidal endothelial cells express a distinctive set of cell-adhesion molecules, adapted to their structural and microenvironmental characteristics, and this repertory is dramatically modified during sinusoidal capillarization, possibly as a consequence of the concomitant matrix changes. PMID- 8362974 TI - Type 1 plasminogen activator inhibitor gene expression following partial hepatectomy. AB - A murine model of partial hepatectomy (PH) was employed to investigate type 1 plasminogen activator inhibitor (PAI-1) gene expression in regenerating liver. Mice were anesthetized, and a portion of the left lobe of the liver was ligated and resected distal to the ligature, and at various times thereafter, total liver RNA was prepared and analyzed by Northern blotting. PH caused a transient increase in PAI-1 messenger (m)RNA that was apparent within 1 to 2 hours after surgery, was maximal at 8 hours (ninefold increase over sham-operated controls), and then slowly declined. Analysis of discrete liver segments demonstrated much greater induction of PAI-1 mRNA in the region adjacent to PH than in more distal regions. Further analysis of the adjacent tissue by in situ hybridization revealed that PAI-1 mRNA was induced primarily in hepatocytes in the transition zone created by the occluding hemostatic ligature between viable and necrotic tissue. Expression of PAI-1 mRNA could also be detected in this transition zone in capsular mesothelial cells, subcapsular hepatocytes, and venous endothelial cells bordering the area. A much weaker signal was evident in hepatocytes dispersed throughout the remaining intact lobes of PH mice, and no signal was detected in the livers of sham-operated mice. These observations suggest that PAI 1 may be of importance in local tissue remodeling events accompanying liver regeneration. PMID- 8362975 TI - Platelet activation releases megakaryocyte-synthesized apolipoprotein J, a highly abundant protein in atheromatous lesions. AB - Apolipoprotein J (apoJ) is an abundant glycoprotein in many biological fluids, and its constitutive high level synthesis is characteristic of many epithelial cells exposed to harsh fluids such as urine, bile, and gastric secretions. In addition, dramatic induction of apoJ occurs in cells surrounding several kinds of pathological lesions. Because platelets and circulating inflammatory cells represent critical elements in numerous pathological processes, we evaluated bone marrow cells for the presence of apoJ. Based upon messenger RNA in situ hybridization and immunofluorescent protein detection, high-level apoJ gene expression and protein accumulation occurred exclusively in mature megakaryocytes. Our results indicate that apoJ is stored in platelet granules and is released into extracellular fluid following platelet activation. Because atheromatous plaque development involves platelet aggregation and activation, we looked for and found abundant apoJ protein in advanced human atheromatous lesions. Thus, platelet sequestration and activation may lead to the rapid deployment of apoJ into sites of vascular injury. We hypothesize that platelet derived apoJ participates in both short-term wound repair processes and chronic pathogenic processes at vascular interfaces. PMID- 8362976 TI - Distribution of ICAM-3-bearing cells in normal human tissues. Expression of a novel counter-receptor for LFA-1 in epidermal Langerhans cells. AB - The LFA-1 integrin mediates its function in leukocyte intercellular interactions by recognition of at least one of its three identified counter-receptors, intercellular adhesion molecules 1 (ICAM-1), 2, and 3. The ICAM-1 molecule is expressed in an inducible-dependent manner by endothelial and epithelial cells, as well as by other cell types, including leukocytes. On the other hand, ICAM-2 is constitutively expressed mainly by endothelial cells. We have studied the tissue distribution of the ICAM-3 molecule by immunohistochemical staining of lymphoid and nonlymphoid organs. Only cells from the leukocyte lineage were found bearing the ICAM-3 antigen, showing a pattern of expression clearly distinct from those of ICAM-1 and ICAM-2. Interestingly, we have found that ICAM-3 is expressed by epidermal dendritic Langerhans cells as assessed by double immunostaining with antibodies specific for CD1. In contrast, staining of skin sections with anti ICAM-1 and ICAM-2 antibodies showed an undetectable expression of these two molecules on Langerhans cells. However, CD1+ Langerhans cells localized in the paracortical area of dermatopathic lymph nodes expressed both ICAM-1 and ICAM-3 antigens. Our results indicate that ICAM-3 is the main LFA-1 counter-receptor in human resident epidermal Langerhans cells. ICAM-3 may have an important role in T cell antigen stimulation driven by Langerhans cells during skin immune reactions. PMID- 8362977 TI - Eosinophils expressing heparin-binding EGF-like growth factor mRNA localize around lung microvessels in pulmonary hypertension. AB - In pulmonary hypertension, induced in rats breathing high oxygen at normobaric pressure, vascular cell hypertrophy and hyperplasia thicken the walls of lung microvessels (15-100 microns in diameter). Over a 28-day time course, new contractile cells develop from intimal precursor smooth muscle cells, which include intermediate cells and interstitial fibroblasts. Cell labeling studies in vivo have shown that these cells proliferate more than other vascular cells and that most of this activity occurs between 4 and 7 days of hyperoxia. The growth factors responsible for this proliferation are unknown. In the present study, we investigate the expression of mRNA for the epidermal growth factor (EGF)-related protein, heparin-binding EGF-like growth factor (HB-EGF), a newly discovered mitogen for fibroblasts and smooth muscle cells. Northern analysis shows HB-EGF mRNA levels to be low in normal lung but increased 100-fold by day 7 of hyperoxia. In situ hybridization identifies a select group of cells expressing HB EGF mRNA. In normal lung, hybridizing cells are randomly distributed in the alveolar wall and space. By day 7, they increase in number and cluster around the microvessels. Histochemical techniques identify cells expressing HB-EGF mRNA as eosinophils. PMID- 8362978 TI - The production of interleukin-1 receptor antagonist by human bronchogenic carcinoma. AB - Bronchogenic carcinoma displays an aggressive clinical course that may reflect a capacity to evade host defenses. We postulated that tumors may elaborate interleukin-1 receptor antagonist protein (IRAP) to escape host interleukin-1 dependent responses. Homogenates of human bronchogenic lung tumors demonstrated significant increases of IRAP compared with normal lung tissue controls (n = 48). There was no significant difference in interleukin-1 beta levels between tumor and normal lung tissue. Immunohistochemical staining localized IRAP to tumor cells. Semiquantitative pathological analysis demonstrated a modest inflammatory cell infiltrate with qualitative differences between tumors of different histology. Western blot analysis of tumor homogenates demonstrated several molecular weight forms of IRAP. Finally, antigenic IRAP was detected in supernatants of the human bronchogenic carcinoma cell line (A549) maintained in vitro. These findings illustrate the capacity of bronchogenic tumors to produce and secrete IRAP that may be important in tumor evasion of host defenses. PMID- 8362979 TI - Effects of human immunodeficiency virus sera and macrophage supernatants on mesangial cell proliferation and matrix synthesis. AB - Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection. PMID- 8362980 TI - Abnormal cytoskeletal assembly in platelets from uremic patients. AB - The mechanisms involved in the hemostatic abnormality of uremic patients remain obscure. We have explored the response of normal and uremic platelets to surface activation at the ultrastructural level and analyzed changes in the composition of proteins associated with normal and uremic platelet cytoskeletons after stimulation with thrombin (0.01 and 0.1 U/ml). Cytoskeletons were obtained by extraction with Triton X-100, processed by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and the presence of cytoskeletal proteins analyzed by densitometry. Under static conditions, uremic platelets spread with difficulty on formvar-coated grids. The percentage of platelets that spread fully on this polymer surface was statistically reduced compared with that of control platelets (11 +/- 1.4 vs. 21 +/- 1.6; P < 0.05). An impairment of cytoskeletal organization was observed in resting uremic platelets but abnormalities were more evident after thrombin activation. The incorporation of actin into the cytoskeletons of thrombin-stimulated uremic platelets was significantly reduced with respect to controls (6 +/- 3% vs. 29 +/- 5%; P < 0.01 after 0.01 U/ml and 28 +/- 9% vs. 59 +/- 10%; P < 0.05 after 0.1 U/ml). Decreased associations of actin-binding protein (P < 0.01), alpha-actinin (P < 0.05), and tropomyosin (P < 0.05) with the cytoskeletons of uremic platelets were also noted. No difference was observed for the incorporation of myosin into the cytoskeletons of activated uremic platelets. These results suggest functional and biochemical alterations of the platelet cytoskeleton in uremia, which may contribute to the impairment of platelet function observed in uremic patients. PMID- 8362981 TI - Response of macaque bronchiolar epithelium to ambient concentrations of ozone. AB - Recently, we reported that exposure to ambient concentrations of ozone, near the U.S. National Ambient Air Quality Standard (0.12 ppm), induced significant nasal epithelial lesions in a non-human primate, the bonnet monkey. The present study defines the effects of ambient concentrations of ozone on the surface epithelium lining respiratory bronchioles and on the underlying bronchiolar interstitium in these same monkeys. Bonnet monkeys were exposed to filtered air or to 0.15 or 0.30 ppm ozone 8 hours/day for 6 or 90 days. At the end of exposures, monkeys were anesthetized and killed by exsanguination. Microdissected bronchiolar airways of infusion-fixed lungs were evaluated morphometrically by light microscopy and quantitatively by scanning and transmission electron microscopy for ozone-induced epithelial changes. Hyperplasia of nonciliated, cuboidal epithelial cells and intraluminal accumulation of macrophages characterized ozone induced lesions in respiratory bronchioles. There were no significant differences in epithelial thickness or cell numbers among ozone-exposed groups. Ozone-exposed epithelium was composed of 80% cuboidal and 20% squamous cells compared with 40% cuboidal and 60% squamous cells in filtered air controls. In addition, the arithmetic mean thickness of the surface epithelium, a measure of tissue mass per unit area of basal lamina, was significantly increased in all of the ozone exposed groups. The number of cuboidal epithelial cells per surface area of basal lamina was increased above control values by 780% after 6 days exposure to 0.15 ppm, 777% after 90 days to 0.15 ppm, and 996% after 90 days exposure to 0.30 ppm. There was also a significant ozone-induced increase in the thickness of the bronchiolar interstitium that was due to an increase in both cellular and acellular components. These results demonstrate that exposure to low ambient concentrations of ozone, near the current. National Ambient Air Quality Standard, induces pulmonary lesions in primates. The alterations do not appear to be concentration- or time-dependent, suggesting that the current National Ambient Air Quality Standard may be at or above the threshold for deep lung injury in primates. PMID- 8362982 TI - Glycoprotein CD44 expression and its association with survival in breast cancer. AB - To investigate the clinical significance of CD44 expression (lymphocyte-homing receptor) in adenocarcinoma, deparaffinized sections from 198 female breast carcinomas were stained with Hermes-3 MoAb for CD44 glycoprotein. In 16% of the cancers most (> or = 90%) of the cancer cells stained positively for CD44, whereas the rest of the cancers were either heterogenous (46%) or negative (38%) in CD44 staining. Cancers with > 50% CD44 positive cells were more often poorly differentiated (grade 3) than those with < or = 50% positive cells (38 vs. 19%, P = 0.006), they had higher mitotic counts (P = 0.04), and were more often estrogen receptor negative (52 vs. 31%, P = 0.01). Among ductal not otherwise specified cancers and node-positive cancers strong CD44 expression was associated with poor outcome (P = 0.05 and 0.02, respectively). However, CD44 expression was not an independent prognostic factor in these subgroups in a multivariate analysis. Unlike in lymphomas the unfavorable prognosis associated with CD44 expression may not be explained by the greater metastatic potential of CD44-positive cells, because the difference in mortality between the groups appeared to diminish with time, and CD44 positivity was associated with aggressive histological features. PMID- 8362983 TI - Atheromatous plaque macrophages produce plasminogen activator inhibitor type-1 and stimulate its production by endothelial cells and vascular smooth muscle cells. AB - The capacity of macrophages to influence directly and indirectly fibrinolytic processes in atherosclerosis was studied using macrophages isolated from atherosclerotic plaques of patients undergoing surgical repair of distal aortic and femoral arteries. These cells were characterized by their morphology, adherence, esterase positivity, and expression of CD14 antigen. Production of plasminogen activator inhibitor type-1 (PAI-1) by plaque macrophages (6.7 +/- 2.7 ng/10(5) cells/24 hours [mean +/- SEM]) was significantly greater than PAI-1 production by blood monocytes isolated simultaneously from the same patients (1.8 +/- 1.5 ng/10(5) cells/24 hours). Production of tissue type plasminogen activator and urokinase type was not augmented compared to blood monocytes. Conditioned medium from cultured plaque macrophages significantly increased production of PAI 1 by endothelial cells (85 +/- 11% above basal) and vascular smooth muscle cells (25 +/- 10%) in vitro. This response was significantly greater than the response to monocyte-conditioned medium (endothelial cells 38 +/- 11%, vascular smooth muscle cells 2.5 +/- 2.0%). Stimulation of endothelial cell PAI-1 production by macrophage-conditioned medium was partially inhibitable by a monoclonal antibody to transforming growth factor-beta. Tissue type plasminogen activator production by endothelial cells and vascular smooth muscle cells was not affected by plaque macrophage- or monocyte-conditioned medium. Urokinase type plasminogen activator production by endothelial cells and vascular smooth muscle cells was undetectable in control medium and was augmented to similar levels in response to plaque macrophage- and monocyte-conditioned media. These results demonstrate upregulation of PAI-1 production by macrophages in atheromatous plaques and the capacity of soluble products from plaque macrophages to upregulate PAI-1 production by endothelial cells and vascular smooth muscle cells in vitro. These data suggest that macrophages in atherosclerotic plaques may inhibit thrombolysis both directly and indirectly by effects of their soluble products on endothelial cells and vascular smooth muscle cells. PMID- 8362984 TI - Serine protease inhibitor antithrombin III and its messenger RNA in the pathogenesis of Alzheimer's disease. AB - The classical plasma protein antithrombin III (ATIII), an inhibitor of the blood coagulation cascade, is a member of the serpins that are gaining import in the nervous system. In this study, we examined the presence of ATIII in the pathological lesions of Alzheimer's disease (AD). Antibodies to ATIII consistently detected approximately 58-kd protein(s) on immunoblots of cerebral cortex and brain microvessels. Immunocytochemical studies showed ATIII reactivity within amyloid deposits, neurites associated with plaques, and neurofibrillary tangles in neocortex and hippocampus of virtually all the AD cases examined. In some cases, astrocytes were also stained, suggesting ATIII in these cells. ATIII immunoreactivity in neurofibrillary tangles was further defined by electron microscopy, which showed it to be associated with paired helical filaments. Using the polymerase chain reaction technique to amplify ATIII complementary DNA, we found low levels of messenger RNA expression, relative to liver, in control human brain samples, and these were increased in AD samples, particularly in the white matter. Our results suggest the increased presence of ATIII commensurate with astrogliosis and association with the neurofibrillary pathology of AD. We conclude that in concert with other amyloid-associated serine protease inhibitors, ATIII may play a role in the pathogenesis of cerebral amyloidosis. PMID- 8362985 TI - Microtubule antagonists activate programmed cell death (apoptosis) in cultured rat hepatocytes. AB - We investigated the mechanism of lethal injury following the disruption of microtubules in cultured hepatocytes treated with vinblastine (VBL) or colchicine (COL). These agents kill hepatocytes by a process readily distinguished from two well-known pathways that lead to a loss of viability, namely, oxidative stress and inhibition of mitochondrial electron transport. Cell killing with VBL and COL was accompanied by fragmentation of DNA. Both the loss of viability and the fragmentation of DNA were prevented by the inhibition of protein synthesis within 6 hours following exposure to VBL or COL. Cell death and the fragmentation of DNA were also prevented when Ca2+ was removed from the culture medium. By contrast, the inhibition of protein kinase C prevented cell killing by VBL or COL, but did not alter the extent of DNA fragmentation. The requirements here for protein synthesis, extracellular Ca2+, and protein kinase C activity define a model of apoptosis, or programmed cell death, that seems to involve mechanisms that can be dissociated from the fragmentation of DNA. PMID- 8362986 TI - Microtubule disruption stimulates DNA synthesis in bovine endothelial cells and potentiates cellular response to basic fibroblast growth factor. AB - Cultured endothelial cells characteristically form a monolayer and become quiescent at saturation density. This study shows that microtubule destabilization in confluent cultures of bovine aortic endothelial cells stimulates fibroblast growth factor 2 (FGF-2, bFGF)-dependent DNA synthesis. Twenty-four hours after addition of the microtubule-disrupting drug colchicine, tritiated thymidine incorporation increases up to fivefold when compared to control cultures. Significant stimulation is seen with doses from 0.05 to 1.0 microgram/ml. The effect of colchicine is quantitatively similar to stimulation of the same cultures with 5 ng/ml FGF-2. Furthermore, the stimulation of DNA synthesis by colchicine can be completely blocked by the addition of a neutralizing antibody to FGF-2. This suggests that colchicine may stimulate bovine aortic endothelial cells by modulating endogenous FGF-2/receptor interactions or that colchicine acts by a different mechanism that requires the growth factor for mitogenicity. The combined effects of colchicine and FGF-2 are more than additive, which supports the idea that microtubule disruption may facilitate cellular response to FGF-2. Cytochalasin B, preventing actin polymerization, inhibits the mitogenic response to FGF-2 but not the response to colchicine. These results are best interpreted as evidence that colchicine stimulates endothelial cell DNA synthesis by a pathway that requires endogenous FGF-2 and may be facilitating cellular responsiveness to the growth factor by disrupting the monolayer via the cytoskeleton. PMID- 8362987 TI - Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA. AB - Hepatocyte growth factor, also known as scatter factor, is a complete mitogen for hepatocytes that bears sequence and structural homology with plasminogen. Because it exists in both a mitogenically inactive single-chain form and an active two chain form, we were interested in determining whether plasminogen activators could properly cleave single-chain hepatocyte growth factor to generate active two-chain hepatocyte growth factor. Herein we report that both urokinase-type plasminogen activator and tissue-type plasminogen activator can cleave single chain hepatocyte growth factor, generating two-chain hepatocyte growth factor. When equal quantities of plasminogen activator-treated and activator-untreated hepatocyte growth factor are compared in serum-free in vitro bioassays, the treated hepatocyte growth factor is mitotically more active. Also, urokinase-type plasminogen activator was inactive against hepatocyte growth factor molecules with a mutated cleavage site. This suggests that urokinase-type and tissue-type plasminogen activator may be natural biological regulators of hepatocyte growth factor. Because the active form of hepatocyte growth factor is a powerful stimulator of DNA synthesis and cell motility, these findings may be relevant in understanding the role of plasminogen activators in the biology of cancer invasion and metastasis. PMID- 8362988 TI - Chronic Lyme borreliosis in the laboratory mouse. AB - C3H/HeJ mice were inoculated intraperitoneally with 10(7) uncloned Borrelia burgdorferi at 4 weeks of age and examined on days 30, 90, 180, and 360. Spirochetes were isolated from multiple tissues at all intervals. Joint and heart disease were present in all mice at 30 days and resolved after 90 days. At 180 and 360 days, some mice had mild recurrent joint and heart disease, and most had peripheral segmental periarteritis. The protein electrophoretic migration of 360 day isolates differed from the original inoculum. The experiment was repeated with C3H/HeN and BALB/cByJ mice inoculated intradermally with 10(4) cloned B. burgdorferi. Characterization of infection and disease at 180 and 360 days were similar to those of the first experiment, but spirochetal proteins of isolates from both intervals displayed no protein variation in electrophoretic mobilities. Spirochetes isolated at 360 days were fully pathogenic in naive mice. Sera from infected mice showed an initial immunoglobulin M response, followed by a sustained immunoglobulin G response, involving IgG1, IgG2a, IgG2b and IgG3, with expanding reactivity against multiple antigens over time. These results indicate that immunocompetent mice sustain persistent infections and develop early acute joint and heart lesions that resolve and then recur intermittently. PMID- 8362989 TI - A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice. AB - Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and tail are not involved. The lesions are characterized by epidermal hyperplasia, hyper- and parakeratosis, and single cell necrosis of keratinocytes. The dermis and epidermis are infiltrated by granulocytes and macrophages, and occasionally subcorneal and intracorneal microabscesses are formed. The number of mast cells in the dermis progressively increases with age. There is dilatation and proliferation of dermal capillaries. Similar lesions develop in the mouth, esophagus, and forestomach, which, in the mouse, are all lined by orthokeratinizing stratified squamous cell epithelium. Studies with bromodeoxyuridine confirm the increased rate of epithelial cell proliferation. Most inflammatory cells in the affected skin express Mac-1, and few express the T lymphocyte marker CD3. There is increased expression of intracellular adhesion molecule-1 on keratinocytes and endothelial cells. Infiltration of neutrophils and macrophages are also seen in the liver, lung, and several joints. The disease could not be transferred by bone marrow or spleen transplants into irradiated normal syngeneic hosts. Treatment of the mice with triamcinolone, a long-acting corticosteroid, resulted in nearly complete regression of the lesions over a period of 4 weeks, whereas systemic cyclosporin A treatment was ineffective. PMID- 8362990 TI - Women and smoking. PMID- 8362991 TI - Toward a smoke-free society: opportunities and obstacles. PMID- 8362992 TI - Smoking control in the 1990s: a national cancer institute model for change. PMID- 8362993 TI - Profits of doom. PMID- 8362995 TI - Commitment to the common good. PMID- 8362994 TI - The tobacco industry, state politics, and tobacco education in California. AB - OBJECTIVES: Proposition 99 added 25 cents to the California state cigarette tax and mandated that 20% of the new revenues be spent on tobacco education and prevention programs. This paper examines the implementation of these programs and the tobacco industry's response to Proposition 99. METHODS: Political expenditure data for twelve tobacco firms and associations were gathered from California's Fair Political Practices Commission and secretary of state's Political Reform Division. Tobacco education expenditure data were collected from Governor's Budgets and the Department of Finance. RESULTS: Since Proposition 99 passed, tobacco industry political expenditures in California have risen 10-fold, from $790,050 in the 1985-1986 election to $7,615,091 in the 1991-1992 election. The tobacco industry is contributing more heavily to the California legislature than to Congress. A statistical analysis of data on campaign contributions indicates that California legislators' policy-making is influenced by campaign contributions from the tobacco industry. Since fiscal year 1989-1990, the state has ignored the voters' mandate and spent only 14.7% of the new revenues to tobacco education. Medical care programs received more money than permitted by the voters. CONCLUSIONS: The tobacco industry has become politically active in California following the passage of Proposition 99. One result may be that the state has underfunded tobacco education by $174.7 million through the 1993-1994 fiscal year. The estimated redirection of funds to medical care would essentially eliminate the tobacco education campaign by the year 2000. PMID- 8362996 TI - Integrating smoking control policies into employee benefits: a survey of large California corporations. AB - OBJECTIVES: Public health policy promotes the use of risk-rating health insurance and payment for smoking cessation as economic incentives to encourage smoking cessation. This study was undertaken to learn more about the adoption of these policies in large corporations. METHODS: A random sample survey of 280 private California corporations with more than 500 employees was undertaken to document the prevalence of policies integrating smoking control into employee benefit designs. RESULTS: Only 8.6% of large corporations had ever considered risk-rating health insurance premiums using smoking status and only 2.15% had implemented a risk-rating policy. Nearly 20% of the companies offered health insurance plans that covered smoking cessation services. Subsidization or payment for smoking cessation outside health insurance was provided by over 37% of the companies surveyed, and 87% had adopted formal work-site smoking policies. CONCLUSION: Benefit policies that provide financial support to smokers to participate in smoking cessation services are much more prevalent and are viewed more positively by the benefits managers in large corporations than are policies to risk-rate health insurance premiums on the basis of smoking. PMID- 8362998 TI - The long-term prevention of tobacco use among junior high school students: classroom and telephone interventions. AB - OBJECTIVES: The purpose of this study was to implement and evaluate the effectiveness of a long-term tobacco use prevention program for junior high school students that used college undergraduate change agents and telephone boosters. METHODS: A psychosocial intervention combining refusal skills training, contingency management, and other tobacco use prevention methodologies such as telephone and mail boosters was implemented in 11 junior high schools in San Diego County, California. Eleven other junior high schools served as controls. Of the 2668 participants, 57% were White/non-Hispanic, 24% were Hispanic, and 19% were of other racial/ethnic groups. College undergraduates served as change agents for both the classroom and booster interventions, the latter of which was delivered in the third (ninth-grade) year of the program. RESULTS: At the end of the third year, the prevalence of tobacco use within the past month was 14.2% among the intervention students and 22.5% among the controls, yielding an odds ratio of 0.71 for analysis at the school level. CONCLUSIONS: Both college undergraduate change agents and direct one-to-one telephone interventions appear to provide cost-effective tobacco-related behavior modification. PMID- 8362997 TI - Work-site cardiovascular risk reduction: a randomized trial of health risk assessment, education, counseling, and incentives. AB - OBJECTIVES: This study reports an efficacy trial of four work-site health promotion programs. It was predicted that strategies making use of behavioral counseling would produce a greater reduction in cardiovascular disease risk factors than screening and educational strategies. METHODS: Twenty-eight work sites were randomly allocated to a health risk assessment, risk factor education, behavioral counseling, or behavioral counseling plus incentives intervention. Participants were assessed before the intervention and at 3, 6, and 12 months. RESULTS: Compared with the average of the health risk assessment and risk factor education conditions, there were significantly higher validated continuous smoking cessation rates and smaller increases in body mass index and estimated percentage of body fat in the two behavioral counseling conditions. The behavioral counseling condition was associated with a greater reduction in mean blood pressure than was the behavioral counseling plus incentives condition. On average among all groups, there was a short-term increase in aerobic capacity followed by a return to baseline levels. CONCLUSIONS: Work-site interventions that use behavioral approaches can produce lasting changes in some cardiovascular risk factors and, if implemented routinely, can have a significant public health impact. PMID- 8362999 TI - Project towards no tobacco use: 1-year behavior outcomes. AB - OBJECTIVES: We present 1-year follow-up data from a school-based tobacco use prevention project designed to test the effectiveness of three main components of social influence programs. The components teach refusal skills, awareness of social misperceptions about tobacco use, and misconceptions about physical consequences. METHODS: Four different curricula were developed and tested in a randomized experiment involving 48 junior high schools. The outcome variables examined were changes in initial and weekly cigarette and smokeless tobacco use 1 year after the intervention. RESULTS: Analyses indicated that each of the component programs were effective in decreasing both the initial and the weekly use of cigarettes except for the curriculum in which refusal skills were taught. Also, each curriculum was effective in decreasing the initial use of smokeless tobacco except for the one aimed at correcting social misperceptions. Only the combined curriculum showed an effect on the weekly use of smokeless tobacco. CONCLUSIONS: The combined intervention was the most effective overall in reducing the initial and weekly use of cigarettes and smokeless tobacco. This suggests that different reasons for use exist and need to be counteracted simultaneously. However, since single programs were also effective in reducing all but weekly smokeless tobacco use, any of these components may be worthwhile prevention tools. PMID- 8363000 TI - Error in smoking measures: effects of intervention on relations of cotinine and carbon monoxide to self-reported smoking. The Lung Health Study Research Group. AB - OBJECTIVES: Sources of measurement error in assessing smoking status are examined. METHODS: The Lung Health Study, a randomized trial in 10 clinical centers, includes 3923 participants in a smoking cessation program and 1964 usual care participants. Smoking at first annual follow-up was assessed by salivary cotinine, expired air carbon monoxide, and self-report. Each of these measures is known to contain some error. Sensitivity and specificity were calculated by comparing a biochemical measure with self-report to produce an undifferentiated estimate of error. Classification error rates due to imprecision of the biochemical measures and to the error in self-report were estimated separately. RESULTS: For cotinine compared with self-report, the sensitivity was 99.0% and the specificity 91.5%. For carbon monoxide compared with self-report, the sensitivity was 93.7% and the specificity 87.2%. The classification error attributed to self-report, estimated by comparing the results from intervention and control groups, was associated with the responses of 3% and 5% of participants, indicating a small but significant bias toward a socially desirable response. CONCLUSIONS: In absolute terms in these data, both types of error were small. PMID- 8363001 TI - Age patterns of smoking in US black and white women of childbearing age. AB - OBJECTIVES: The purpose of the study was to describe age patterns of smoking among Black and White women of reproductive age, with cohort membership controlled for. METHOD: Data from the 1987 National Health Interview Survey Cancer Supplement, weighted to be nationally representative, were used to calculate the fractions of women who were ever smokers, quitters, and current smokers by age and race. Summary distributions of age patterns of smoking behaviors by race were estimated; proportional hazard models were used to avoid confounding of age and cohort. RESULTS: White women begin smoking at younger ages than do Blacks but are more likely to quit and to do so at young ages. Rates of current smoking converge between Blacks and Whites by age 25, and may cross over by 30. Education-standardized results show larger Black-White differentials in ever smoking and smaller differences in quitting. CONCLUSIONS: Our findings confirm that women's age patterns of smoking vary by race. Age x race interactions should be considered in smoking research and anti-tobacco interventions. For Black women, delayed initiation and failure to quit call for increased emphasis on interventions tailored to adults. These findings have possible implications for understanding Black-White differences in low birthweight, child health, and women's health. PMID- 8363002 TI - Cigarette smoking and bone mineral density in older men and women. AB - OBJECTIVES: The association between cigarette smoking and bone mineral density was examined prospectively in a population-based study of older Caucasian men and women. METHODS: Smoking patterns were determined at a 1972-1974 baseline evaluation and, again, 16 years later when 544 men and 822 women had bone mineral density measurements taken. RESULTS: Men and women who were cigarette smokers at baseline demonstrated significantly reduced bone mineral density of the hip compared with nonsmokers. Baseline smoking was not associated with significantly lower bone density at non-hip sites. Women demonstrated a significant dose response relationship between baseline smoking status at all hip sites measured. Both sexes exhibited significant dose-response relationships between hip bone mineral density and change in smoking status between baseline and follow-up, demonstrating that smoking cessation in later life was beneficial in halting bone density loss associated with smoking. CONCLUSIONS: Smoking was positively and significantly associated with decreased hip bone mineral density in old age. Bone loss associated with smoking would be expected to predict an increased risk of hip fracture in those who do not succumb earlier to another complication of tobacco use. PMID- 8363003 TI - Tobacco use: a modifiable risk factor for dental disease among the elderly. AB - OBJECTIVES: Because the public health literature contains few analytic studies of modifiable behavioral risk factors for dental disease among older community dwelling populations, the New England Elders Dental Study was undertaken as an epidemiologic study of the oral health status of a representative sample of older adults living within the six New England states. METHODS: Five dentists conducted comprehensive in-home oral health examinations on 1156 community-dwelling adults aged 70 and older to determine whether lifetime use of tobacco products was a significant risk factor for tooth loss, caries, and periodontal disease. RESULTS: Among New England elders, tobacco use was more common among men (18.1%) than women (7.9%), with a combined rate of 12.3%. Further, 64.7% of men and 36.6% of women were previous tobacco users. Years of exposure to tobacco products was a statistically significant risk factor for tooth loss, coronal and root caries, and periodontal disease, regardless of other social and behavioral factors. CONCLUSIONS: Lifelong tobacco use is a modifiable risk factor for poor dental health among older adults. Dental practitioners need to intervene with all their adult patients to discourage use of tobacco products for oral as well as general preventive health care. PMID- 8363004 TI - Smoking, alcohol consumption, and susceptibility to the common cold. AB - OBJECTIVES: This study was conducted to test the supposition that both smoking and consuming alcohol suppress host resistance to viral infections. METHODS: The relations between smoking, alcohol consumption, and the incidence of documented clinical colds were prospectively studied among 391 subjects intentionally exposed to one of five respiratory viruses and 26 subjects given saline. Clinical colds were defined as clinical symptoms verified by the isolation of virus or by an increase in virus-specific antibody titer. Analyses included control variables for demographics; body weight; virus; and environmental, immunological and psychological factors. RESULTS: Smokers were at greater risk for developing colds than nonsmokers because smokers were more likely both to develop infections and to develop illness following infection. Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness following infection. However, the benefits of drinking occurred only among nonsmokers. CONCLUSIONS: Susceptibility to colds was increased by smoking. Although alcohol consumption did not influence risk of clinical illness for smokers, moderate alcohol consumption was associated with decreased risk for nonsmokers. PMID- 8363005 TI - Smoking control in restaurants: the effectiveness of self-regulation in Australia. AB - OBJECTIVES: The provision of smoke-free areas in restaurants has been a controversial issue; the restaurant industry largely opts for a self-regulation approach. This study aimed to examine the effectiveness of self-regulation as a strategy in meeting the industry's and customers' perceived needs. METHODS: Restaurateur and customer perspectives on the provision of smoke-free areas in restaurants were examined by survey among 365 restaurateurs and 1327 customers in New South Wales, Australia. RESULTS: Less than 2% of restaurants were totally smoke-free; 22% provided some smoke-free areas. Customers were much more likely than owners to think that smoke-free areas should be provided. Owners appeared to be unaware of customers' views about smoke-free areas in restaurants. CONCLUSIONS: Little evidence was found to support the effectiveness of the self regulation policy adopted by the restaurant industry. Characteristics of restaurants and owners associated with the provision of smoke-free areas are presented and implications of the findings are discussed. PMID- 8363006 TI - Health insurance and subjective health status: data from the 1987 National Medical Expenditure survey. AB - OBJECTIVES: The relationship between health insurance and subjective health status was investigated. It was hypothesized that persons without health insurance would have lower levels of subjective health status than those with health insurance and that this relationship would hold for both poor and nonpoor persons. METHODS: Data from the 1987 National Medical Expenditure Survey were analyzed to examine the relationship between health insurance and self-reported health status. The analysis controlled for sociodemographic and attitudinal variables and medical conditions. RESULTS: Persons without health insurance had significantly lower levels of subjective health status than did persons with insurance. This adverse effect persisted after adjustments were made for the effects of age, sex, race, income, attitude toward the value of medical care and health insurance, and medical conditions. The detrimental effect of lacking health insurance on subjective health status was present for persons at all income levels and was greater than the effect on subjective health status found for 2 of the 11 reported medical conditions. CONCLUSIONS: Lacking health insurance is associated with clinically significant lower levels of subjective health status in both poor and non-poor persons. PMID- 8363007 TI - The distribution of canine exposure to Borrelia burgdorferi in a Lyme-Disease endemic area. AB - OBJECTIVES: A serosurvey of canine exposure to Borrelia burgdorferi, the causative agent of human Lyme disease, was conducted in Westchester County, New York, to determine the distribution of exposure in an area endemic for Lyme disease. METHODS: A total of 1446 blood samples was collected from resident dogs and tested by modified enzyme-linked immunosorbent assay. Equivocal samples were further tested by immunoblot. A mean number of 57.8 samples was collected from each of 25 towns and cities. RESULTS: Seroprevalence rates for municipalities ranged from 6.5% to 85.2%. County seroprevalence was 49.2%. There was a significant difference among the rates for the northern (67.3%), central (45.2%), and southern (17.3%) regions. Multiple range analysis indicated homogeneity between the southern and central regions and the central and northern regions. CONCLUSIONS: Canine exposure to B burgdorferi increases in a south to north gradient within the county. Intensity of exposure, measured by enzyme-linked immunosorbent assay titers, indicates a similar pattern. The close association between dogs and humans suggests that human risk of acquiring Lyme disease within Westchester County is equally disparate and is inversely related to the degree of urbanization. PMID- 8363008 TI - Occupation as a risk identifier for breast cancer. AB - OBJECTIVES: Breast cancer mortality may be reduced if the disease is detected early through targeted screening programs. Current screening guidelines are based solely on a woman's age. Because working populations are accessible for intervention, occupational identification may be a way of helping to define and locate risk groups and target prevention. METHODS: We used a database consisting of 2.9 million occupationally coded death certificates collected from 23 states between 1979 and 1987 to calculate age-adjusted, race-specific proportionate mortality ratios for breast cancer according to occupation. We performed case control analyses on occupational groups and on stratifications within the teaching profession. RESULTS: We found a number of significant associations between occupation and frequency of breast cancer. For example, white female professional, managerial, and clerical workers all had high proportions of breast cancer death. High rates of breast cancer in teachers were found in both proportionate mortality ratio and case-control analyses. CONCLUSIONS: These findings may serve as in an aid in the effective targeting of work-site health promotion programs. They suggest that occupationally coded mortality data can be a useful adjunct in the difficult task of identifying groups at risk of preventable disease. PMID- 8363010 TI - Child care arrangements and repeated ear infections in young children. AB - OBJECTIVES: The purpose of this study was to assess the association between child care arrangements and repeated ear infections in young children. METHODS: Data on 5818 children younger than 6 years of age were taken from the 1988 National Health Interview Survey of Child Health. RESULTS: Seventeen percent of the children had had repeated ear infections in the year preceding the interview. Multiple logistic regression analysis showed that factors significantly associated with repeated ear infections were age (1 to 2 years), race (White), sex (male), and medical history (repeated tonsillitis, enlarged adenoids, or asthma). When these factors were controlled for, children in a current child care arrangement still had a 50% higher chance of repeated ear infections than did children not in care. Children in day care centers were at higher risk than children cared for in homes. Care in settings with more than six children elevated the risk, but hours per week of care did not. CONCLUSIONS: Decreasing the risk of repeated ear infections in young children in out-of-home child care settings may require smaller group sizes. Given the increasing use of child care, research should continue to identify specific aspects of child care that contribute to this problem. PMID- 8363009 TI - Cervical cancer screening in hospitals: the efficacy of legislation in Maryland. AB - OBJECTIVES: The purpose of the study was to examine the efficacy of a Maryland law requiring Pap testing to be offered during hospital admissions. "In-reach" strategies emphasize cancer screening within existing health care contacts (such as inpatient stays) rather than additional visits solely for screening. METHODS: Data from a 1986 telephone survey of Maryland women were used to examine the effect of hospitalization on self-reported Pap testing in a 3-year period. The effect of hospitalization on screening was examined by age and income to assess whether inpatient screening was more prevalent among certain subgroups of women. RESULTS: For the group as a whole, the odds of Pap screening did not vary with hospitalization. However, among women aged 45 to 54 years with annual household incomes over $20,000, hospitalized women were more likely than nonhospitalized women to report recent Pap tests. For low-income women aged 75 years and older, hospitalization actually decreased the likelihood of reporting Pap tests. CONCLUSIONS: Despite legislation, inpatient cervical cancer screening appears to mirror outpatient patterns, leaving elderly and low-income women unscreened. Methods for increasing inpatient Pap testing for underscreened women are discussed. PMID- 8363012 TI - The influence of smoking cessation on body weight may be temporary. AB - The relationships of bodyweight and body mass index with smoking cessation were examined among 1633 adults in Humboldt, Saskatchewan, Canada. Mean body mass index was highest in ex-smokers and lowest in smokers, and that of non-smokers was intermediate. Body mass index decreased significantly with increasing years after smoking cessation in female ex-smokers after adjusting for age, education, location of work, and physical activity. This trend, however, was not significant in men. The body weight data showed similar results. The prevalence of obesity (body mass index greater than 30 kg/m2) in all subjects showed a decrease with increasing years after smoking cessation. PMID- 8363011 TI - Respiratory disease among military personnel in Saudi Arabia during Operation Desert Shield. AB - OBJECTIVES: The purpose of this study was to determine whether respiratory disease due to crowded living conditions and high levels of suspended and blowing sand had a major adverse impact on US military personnel during Operation Desert Shield. METHODS: A questionnaire survey was administered to 2598 combat troops stationed in Northeast Saudi Arabia for a mean of 102 days. Samples of surface sand from seven different locations were analyzed by scanning electron microscopy and x-ray diffraction. RESULTS: Among surveyed troops, 34.4% reported a sore throat, 43.1% complained of a cough, 15.4% complained of chronic rhinorrhea, and 1.8% were unable to perform their routine duties because of upper respiratory symptoms. Evaluation of sleeping accommodations indicated that complaints of a sore throat and cough were most closely associated with sleeping in air conditioned buildings; in contrast, complaints of rhinorrhea were associated with exposure to the outdoor environment while living in tents. Sand samples consisted mostly of quartz, with just 0.21% by weight of respirable size (< 10 microns in diameter). CONCLUSIONS: These findings indicate that upper respiratory complaints were frequent among Operation Desert Shield troops and were related both to the troops' housing and to their exposure to the outside environment. PMID- 8363013 TI - Factors associated with late smoking initiation in Minnesota women. AB - This case-control study investigated factors associated with late initiation (i.e., initiation after the age of 17 years) of smoking among young women. The most significantly elevated odds ratios for late initiation were having a significant other who smoked and having friends who found smoking acceptable at initiation. Peers, especially significant others, played an important role in smoking initiation among young women. Prevention efforts should focus on strategies that reduce the acceptability of smoking in the social environment. PMID- 8363014 TI - Cotinine concentrations in semen, urine, and blood of smokers and nonsmokers. AB - Cotinine levels in the semen, urine, and blood of 88 male smokers and nonsmokers, aged 18 to 35, were analyzed via radioimmunoassay. Detectable cotinine levels were found in all three body fluids, and cotinine levels in all three fluids were highly correlated. Cotinine levels in semen and blood were of similar magnitude; cotinine levels in urine were an order of magnitude or more higher. In all three fluids, cotinine levels increased with an increase in cigarette smoke exposure. PMID- 8363015 TI - Environmental tobacco smoke concentrations in no-smoking and smoking sections of restaurants. AB - To characterize the effectiveness of a local ordinance that restricts smoking in restaurants to one third of the seating area, this study made simultaneous measurements of two markers of environmental tobacco smoke, respirable suspended particles and nicotine, in the smoking and no-smoking sections of seven restaurants. The mean concentrations of respirable suspended particles and nicotine were 40% and 65% lower, respectively, in the no-smoking than in the smoking sections, indicating substantial but not complete protection against exposure. PMID- 8363016 TI - An evaluation of the workplace smoking bylaw in the city of Toronto. AB - Random-digit dialing surveys were conducted before (n = 1543) and 8 to 9 months after (n = 1430) implementation of the city of Toronto workplace smoking bylaw. Compared with workers in the rest of metropolitan Toronto and persons not working outside the home, city workers evidenced more positive changes in regard to knowledge of the bylaw, its requirements, and enforcement provisions. City workers reported more changes in workplace restrictions and satisfaction with such restrictions. Patterns of smoking at work changed. PMID- 8363017 TI - Smoking, depression, and suicide. PMID- 8363018 TI - Sudden infant death syndrome and maternal smoking conclusions questioned. PMID- 8363019 TI - Chlorination or ozonation? PMID- 8363020 TI - What does America's public health report card reflect? PMID- 8363021 TI - Drug users' self-reported false-positive HIV status. PMID- 8363022 TI - Bias in weighted vs unweighted estimates. PMID- 8363023 TI - The attribution of health problems to aging. PMID- 8363024 TI - [Postoperative pain therapy--an urgent interdisciplinary task]. PMID- 8363026 TI - [Pulmonary CO2 elimination in laparoscopic cholecystectomy. A clinical study]. AB - METHODS: We measured pulmonary elimination of carbon dioxide (VCO2), end-tidal and arterial CO2 tensions (PETCO2, PaCO2), deadspace ventilation (VD/VT), and arterial oxygen tension (PaO2) using a Siemens 930 CO2 analyzer incorporated into a servoventilator and arterial blood gas analyses, respectively, in 31 patients undergoing laparoscopic cholecystectomy with a median duration of pneumoperitoneum (PP) of 60 min. RESULTS: During the first 30 min of PP VCO2 increased significantly by a mean of 30% (Fig. 1). At the same time, with constant minute ventilation PETCO2 und PaCO2 increased by about 8 mm Hg each (Fig. 3, Table 1). In a subgroup of 10 patients who could be observed for up to 75 min of PP, we found a stepwise increase in minute ventilation with no further increase in PETCO2 and PaCO2 after 30 min PP, but a slowly rising VCO2 (Fig. 2). Arterial-to-end-tidal CO2 tension difference (Pa-PETCO2) remained constant at about 4 mm Hg with institution and during the course of PP (Fig. 4), as did VD/VT at a median value of 0.38-0.40 (Fig. 5). PaO2 (FIO2 = 0.5) did not change significantly with PP (Table 1). With desufflation we found a short-term increase in VCO2 (Table 2). CONCLUSIONS: During PP, CO2 is reabsorbed from the peritoneal cavity. During the initial unstable phase with rising PaCO2, reabsorption of CO2 is the sum of increased pulmonary elimination of CO2 above baseline and uptake of CO2 into gas stores of the body. We estimated CO2 reabsorption to be on the order of 70 ml/min during the first 30 min of PP. During the later, stable phase, reabsorption of CO2 equals increased pulmonary elimination of CO2 above baseline and was estimated to be in the order of 90 ml/min in 10 patients with 30-75 min of PP (hatched area in Fig. 2). PET-CO2 corresponded well with PaCO2 in these patients. VD/VT and arterial oxygenation did not change significantly with institution or during the course of PP. Monitoring VCO2 probably is a useful aid in the early detection of CO2 emphysema (Fig. 6). PMID- 8363025 TI - [Fiberoptic intubation and stress]. AB - Nasotracheal intubation of the trachea by means of fiberoptic endoscopy is an accepted approach to difficult airways. The associated avoidance of direct laryngoscopy may affect the stress response to nasotracheal intubation. We tested this hypothesis by means of a prospective, randomized, controlled clinical study. METHODS. Informed consent was obtained from 30 patients presenting for maxillofacial surgery for participation in this study. Patients were allocated to three groups: nasotracheal intubation to be performed either fiberendoscopically (group 1) or laryngoscopically, with (group 2) or without (group 3) topical anaesthesia of the larynx. Haemodynamic variables (arterial blood pressure and heart rate) and concentrations of catecholamines* in plasma (adrenaline, noradrenaline; HPLC) were documented at four (two*) time points, respectively: prior to induction of anaesthesia*, after induction, 1 min after tracheal intubation*, 5 min after tracheal intubation. Differences between time points and between groups were analysed with the chi-square test; a probability of P < 0.05 was considered statistically significant. RESULTS. With respect to age, body weight and gender, the groups were comparable. No major hemodynamic or endocrine stress responses were observed in any group. Diastolic blood pressures were significantly lower in groups one and two, one minute after tracheal intubation. DISCUSSION. Nasotracheal intubation does not provoke a major stress response, when performed in accordance with the protocol of this study. However, topical anaesthesia of the larynx, as well as the fiberendoscopic approach proved superior to control with respect to diastolic arterial pressure. We conclude that fiberoptic nasotracheal intubation, or laryngoscopy preceded by topical anaesthesia of the larynx may be useful in patients for whom an increase in rate pressure product would be undesirable. PMID- 8363027 TI - [ST segment changes in the ECG. Anesthesia induction with propofol, etomidate or midazolam in patients with coronary heart disease]. AB - Induction of anaesthesia with propofol and fentanyl can lead to marked reductions in mean arterial pressure (MAP) and heart rate (HR). Thus, the application of propofol in patients with severely reduced coronary artery perfusion is controversial. METHODS. The study group consisted of 60 patients undergoing coronary artery bypass grafting (CABG). Anaesthesia was induced over 30 s with propofol (P 1.5 mg/kg), etomidate (E 0.3 mg/kg), or midazolam (M 0.15 mg/kg) following a bolus dose of fentanyl (5 micrograms/kg). Vecuronium was used as a muscle relaxant. During induction we continuously measured MAP and HR and recorded the occurrence of myocardial ischaemia using an automatic ST-segment analyser (Marquette 7010). ST-segment deviations of more than 1 mm in leads II and V5 were interpreted as significant signs of myocardial ischaemia. RESULTS. All groups showed reductions in MAP and HR on induction that were marked in the P group. Intubation caused elevation of MAP and HR to pre-induction levels (HR: all groups) or slightly above (MAP: E, M). Four patients in the P group and 3 in each other group showed significant ST-segment deviation prior to induction. In the P group these deviations disappeared in 2 patients after injection while they remained unchanged in the M group. In the E group injection had no effect on the ischaemic ECG changes but produced another case of significant ST-segment deviation. Laryngoscopy and intubation produced no further significant ST-segment deviation in either group. DISCUSSION. Induction is a critical phase of anaesthesia, especially in patients with limited coronary reserve. Induction agents should alleviate the stress response while causing minimal haemodynamic changes. Despite marked reductions in MAP in the P group, the number of patients with ischaemic ECG changes was cut by half. Their number was unchanged or even raised in the other groups. After application of P, with an alleged reduction of coronary perfusion, a compensational reduction in myocardial oxygen consumption may occur. PMID- 8363028 TI - [Continuous monitoring of spontaneous respiration in the postoperative phase. 4. The effect of postoperative pain therapy on cutaneous oxygen and carbon dioxide partial pressure following gynecologic surgery with neuroleptanalgesia]. AB - METHODS: Cutaneous O2 and CO2 pressures were monitored for 16 h in 55 female patients recovering from major gynaecological surgery performed under neurolept anaesthesia. Postoperative pain was managed either with an antipyretic analgesic (i.m. or i.v. metamizol up to 2.5 g/4 h; group NLA) or with i.v. patient controlled analgesia using fentanyl (demand dose 34 micrograms, infusion rate 4 micrograms/h, hourly maximum dose 0.25 mg, lock-out time 1 min; group NLA/PCA). In addition, 11 patients received a single i.v. bolus injection of 150 mg amiphenazole, a respiratory stimulant, at the beginning of PCA treatment (group NLA/PCA/AMI). Data were collected and stored by a personal computer, using the TCM3 system with a combination electrode for simultaneous measurement of cutaneous oxygen and carbon dioxide partial pressures (TINA, Radiometer) at 30-s intervals. The overall observation period was four times 240 min; patients from the NLA group who required additional opioids were excluded from the analysis. Means and standard deviations were calculated for individual data and data pooled for 15- or 60-min intervals. Groups were compared by means of the chi-square test, Student's t-test or analysis of variance (level of significance, P < or = 0.05). RESULTS: The 55 patients were classified as ASA I-II. The study groups were comparable with respect to demographic and anaesthesiological data, except that those in the NLA group were younger and had received less intraoperative fentanyl (Table 1). Mean PCA fentanyl consumption was 0.6-0.7 mg in the 16-h observation period (Table 2). In all groups, pctO2 levels were decreased and pctCO2 levels elevated in the first observation hours and slowly returned to normal within the first observation period (Figs. 1, 2, Tables 3, 4). Episodes of hypercapnia (pct-CO2 > 50 or > 55 mm Hg) were frequent in the first 2 h (8-29% of individual values for pctCO2 > 50, up to 5% of values recorded for pctCO2 > 55; Table 4). There were no statistically significant differences between patients treated with metamizol and those treated with fentanyl. Amiphenazole did not significantly improve postoperative respiration. PCA patients had occasional episodes of hypercapnia (up to 19% of all values for pctCO2 > 50, up to 5% for pctCO2 > 55) even in the last observation period (13-16 h after surgery), indicating the need for close monitoring of spontaneous ventilation during PCA following neurolept anaesthesia. DISCUSSION AND CONCLUSIONS: The present study confirmed that spontaneous respiration in the early postoperative period can be monitored non-invasively by measuring cutaneous partial pressures of carbon dioxide and, less precisely owing to wide individual variations, oxygen. It showed that spontaneous respiration is less effective immediately after termination of surgery under neurolept anaesthesia and recovers slowly over the next 4 h. During the first observation period, ventilation was no worse with i.v. PCA using fentanyl than with conventional pain management using the antipyretic analgesic metamizol, confirming the hypothesis that opioid-induced respiratory depression occurs only at overdosage (which is not a problem with individualized dose titration using PCA). Since all patients in the NLA group required additional opioids after the first observation period and had to be excluded from further analysis, it cannot be decided from the present data whether late hypercapnia was due to PCA or to residual effects of surgery and anaesthesia. The respiratory stimulant amiphenazole (150 mg i.v.) was not helpful in improving ventilation; there was no indication of analgesic effects or interactions of amiphenazole. PMID- 8363030 TI - [The preclinical efficacy of emergency care. A prospective study]. AB - Quality assurance has become an important issue in emergency medicine. At present, no prospective studies are available that quantify the efficacy of interventions performed by emergency doctors. The development and implementation of a rapid, yet simple scoring system, allowing preclinical assessment of all emergency medicine patients, is required. Once the scoring system is implemented, evaluation of the prehospital intervention, based upon objective parameters, is possible. METHODS. The Mainz Emergency Evaluation Score (MEES) is based on seven parameters: level of consciousness, heart rate, heart rhythm, arterial blood pressure, respiratory rate, partial arterial oxygen saturation and pain. A coded value is assigned to each parameter, with the normal physiological condition securing a score of 4, while a life-threatening condition receives a value of 1. For the parameter of pain there is no life-threatening condition, so the lowest value allowed is 2 (Table 2). Addition of the respective values from the seven parameters yields the MEES value, which objectively reflects the patients' condition (minimum = 8, maximum = 28). Comparing the MEES value before (MEES1) and after the intervention (MEES2) allows an objective evaluation of the efficacy of the preclinical care (delta-MEES = MEES2-MEES1). A difference of > or = +2 is considered an improvement, +1, +/- 0, -1 are rated as unchanged and < or = -2 is considered a deterioration in the patients condition. For more detailed evaluation the patients were allocated to 16 diagnosis groups (Table 3). Statistical evaluation utilized analysis of variance, the rank sum test (Wilcoxon) and the correlation coefficient (Kendall-Tau). RESULTS. In 356 patients the condition of 187 (52%) patients improved during the preclinical treatment; the condition of 156 (44%) patients did not change. In 13 patients (3%) the condition became worse (Table 5, Fig. 2). Allocation to 16 diagnosis groups revealed that the improvement in the patient's condition depended on the underlying disease (Table 3); the disease-specific parameter improved in all cases (Table 7). CONCLUSIONS. With the MEES score one can assess the patient's prehospital condition and monitor any improvement or deterioration during subsequent intervention and transport. The MEES was found to be easy to use, reliable and not an additional burden to emergency doctors. The MEES provides a means of assessing the efficacy of preclinical treatment. This score does not allow outcome prediction; this requires the inclusion of hospital data. Assessment of the efficacy of prehospital intervention is an important first step in the inclusion of quality assurance in emergency medical systems. PMID- 8363029 TI - [The incidence of postoperative pain on general surgical wards. Results of different evaluation procedures]. AB - Knowledge of the incidence and significance of postoperative pain is essential for the establishment of effective pain treatment programmes. Detailed investigations on the incidence, severity and quality of postoperative pain from the surgeon's perspective are scarce in German hospitals. It was the aim of our study to investigate postoperative pain in general surgery under routine conditions. PATIENTS AND METHODS. A total of 168 patients scheduled for abdominal, vascular and orthopaedic surgery were investigated in a prospective trial. Pain was assessed by means of a 100-point visual analogue scale (VAS), a 5 point verbal rating scale (VRS), the original version of the McGill Pain Questionnaire (MPQ) and the short form of the McGill Pain Questionnaire (SFMPQ). These were applied preoperatively and daily thereafter up to the 7th postoperative day. Patients were randomly assigned into two groups with different sequences of application of the instruments. The pain treatment programme included intravenous analgesia with tramadol/metamizol (max. tramadol 400 mg+metamizol 5 g in any 24 h) after major surgery and additional administration of piritramide as needed (max. 60 mg/24 h.i.v.). After minor surgery ibuprofen was routinely given for analgesia (3 x 500 mg). RESULTS. All patients had pain on the days 1 and 2 postoperatively. The mean intensity of pain was 44 VAS points on day 1 and 6.8 points on day 7. The mean intensity of pain measured by the VRS on the 1st postoperative day was between "mild" and "moderate". The quality of pain showed a constant pattern concerning the mean scale values of descriptors of each subgroup (sensory, evaluative, affective, mixed) for both the original and the short form of the McGill Pain Questionnaire up to the 7th postoperative day. Sensory descriptors were reported more frequently than affective descriptors. Typical pain patterns were identified for different operations. After subtotal thyroidectomy, for example, patients perceived a high intensity of pain of short duration. In contrast, patients still have a high intensity of pain up to 7 days after abdominal and rectal operations. CONCLUSIONS. We conclude from our results that patients perceive significant postoperative pain under current standardized pain treatment in our department. Effective programmes for pain relief should take account of the different patterns of pain after different operations, as identified in this study. PMID- 8363031 TI - [Anesthesia simulators and training devices]. AB - Simulators and training devices are used extensively by educators in 'high-tech' occupations, especially those requiring an understanding of complex systems and co-ordinated psychomotor skills. Because of advances in computer technology, anaesthetised patients can now be realistically simulated. This paper describes several training devices and a simulator currently being employed in the training of anaesthesia personnel at the University of Florida. This Gainesville Anesthesia Simulator (GAS) comprises a patient mannequin, anaesthesia gas machine, and a full set of normally operating monitoring instruments. The patient can spontaneously breathe, has audible heart and breath sounds, and palpable pulses. The mannequin contains a sophisticated lung model that consumes and eliminates gas according to physiological principles. Interconnected computers controlling the physical signs of the mannequin enable the presentation of a multitude of clinical signs. In addition, the anaesthesia machine, which is functionally intact, has hidden fault activators to challenge the user to correct equipment malfunctions. Concealed sensors monitor the users' actions and responses. A robust data acquisition and control system and a user-friendly scripting language for programming simulation scenarios are key features of GAS and make this system applicable for the training of both the beginning resident and the experienced practitioner. GAS enhances clinical education in anaesthesia by providing a non-threatening environment that fosters learning by doing. Exercises with the simulator are supported by sessions on a number of training devices. These present theoretical and practical interactive courses on the anaesthesia machine and on monitors. An extensive system, for example, introduces the student to the physics and clinical application of transoesophageal echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363032 TI - [Acute obstruction of an anesthetic gas evacuation system. Ventilation with a Servo Ventilator 900D]. AB - During aorto-coronary bypass surgery acute expiratory airway obstruction occurred in two patients during controlled ventilation with a Servo D ventilator (Siemens Elema) in combination with a Servo EVAC 180 gas evacuation system. In this system expiratory volume passes from the ventilator to the reservoir bag. Distension of the bag will open the valve to the receiving unit by vertical dislocation of the valve spring. The mechanism relies on free mobility of the valve spring within the reservoir bag. We observed an increase in mean expiratory and inspiratory airway pressure above 40 mmHg due to blockage of the expiratory gas outlet by external lateral dislocation of the valve spring. In conclusion, while free mobility of the valve spring within the hanging Evac bag has to be ascertained at all times for safe application of the EVAC 180 system, the manufacturer should provide some appropriate mechanical shelter around the bag. PMID- 8363033 TI - [Pseudo-faulty location of a Swan-Ganz catheter in a persistent left superior vena cava]. AB - The insertion of a Swan-Ganz catheter may cause various complications including intravascular malpositioning due to congenital anomalies of the large veins. A persistent left superior vena cava is the most frequent anomaly of the large vessels. It is usually diagnosed either as an incidental finding at autopsy or during X-ray imaging for confirming proper position of central venous and pulmonary catheters. The incidence of this condition based on autopsy series is approximately 0.3%. CASE REPORT. A 52-year-old patient was admitted to the surgical ICU with the diagnosis of acute pancreatitis. Because of haemodynamic instability, a pulmonary artery flotation catheter was inserted via the left subclavian vein without difficult. The chest radiograph showed the catheter along the left border of the heart going into the right pulmonary artery. An angiographic examination with bolus contrast injection confirmed a persistent left superior vena cava. CONCLUSION. This type of malposition calls for further detailed diagnosis of the vascular status, as the knowledge of accompanying congenital cardiovascular defects is essential for further invasive diagnostic and surgical procedures. The intensivist should be aware of its occurrence in order to not mistake catheters as being present in the arterial circulation or malpositioned outside the venous circulation. PMID- 8363034 TI - [Securing the airway in children with the Morquio-Brailsford syndrome]. AB - Mucopolysaccharidosis IVA (Morquio-Brailsford syndrome) results from an inborn deficiency of n-acetyl-galactosamine-6-sulphate sulphatase. Clinical features include skeletal deformities with hypoplasia or absence of the odontoid process of the axis. The resulting atlanto-axial subluxation compresses the spinal cord, resulting in cervical myelopathy. Without treatment, quadriplegia ensues sooner or later; consequently, surgical decompression and dorsal fusion of the cervical vertebrae is recommended, either prophylactically or therapeutically. Anaesthesiological management must focus on protection of the airway without compromising integrity of the cervical spinal cord; quadriplegia subsequent to positioning of the head under anaesthesia has been reported. We have performed fiberendoscopic nasotracheal intubation in a 23-month-old child presenting for neurosurgical treatment of cervical myelopathy resulting from Morquio-Brailsford syndrome. CASE REPORT. A 23-month-old girl (84 cm, 11 kg) with Morquio-Brailsford syndrome presented for surgical decompression and dorsal fusion of the cervical spine. Pre-anaesthetic examination revealed enamel defects, chronic bronchitis, and splenomegaly; the neck was immobilised with a collar. Radiological examinations (X-ray and NMR) revealed narrowing of the atlanto-occipital and atlanto-axial spaces (Fig. 1) and compression of the cervical spinal cord (Figs. 2 and 3). Pre-anaesthetic medication consisted of midazolam juice (4 mg). After establishing intravenous access, atropine (0.5 mg), midazolam (1 mg), and ketamine (10 mg) were administered. A 22 Fr nasopharyngeal airway (Wendl) was lubricated with local anaesthetic gel and introduced into the right nostril; oxygen was administered through a probe to the left nostril. The Wendl-airway was then removed, another 5 mg ketamine was administered, and a 3.5-mm flexible fiberendoscope--over which a 20 Fr armored tube was slipped--was introduced through the right nostril. With the child spontaneously breathing, the glottis was visualised and the fiberscope introduced into the trachea (Fig. 4); 1 mg midazolam and 35 mg ketamine was administered and the endotracheal tube was advanced through the nose into the trachea, utilizing the fiberscope as a guide. The distance between endotracheal tube and carina was assessed endoscopically, the fiberscope withdrawn, and the tube connected to the breathing system. Pulse oxymetric readings were 98% during induction of anaesthesia including endotracheal intubation. Anaesthesia was continued with enflurane, alfentanil, midazolam, and atracurium; 315 min after induction the trachea was extubated and the child discharged to the paediatric intensive care unit. The postsurgical course was uneventful, and the child resumed co-ordinated gait. DISCUSSION. Airway management in patients with mucopolysaccharidoses may be extremely difficult. Recommended methods such as blind nasal intubation are not feasible in small children. Anaesthetic management in children younger than 2 years with Morquio-Brailsford syndrome presenting for cervical spine surgery has not yet been described. Fiberoptically guided nasotracheal intubation is a means of airway management that does not require repositioning of the head and may be performed with the stabilising collar left in place (Fig. 4); preservation of cervical spinal cord integrity may hence be assumed. Analgosedation with ketamine and midazolam allows sufficient spontaneous breathing and--to some extent- maintenance of protective laryngeal reflexes. In conclusion, anaesthetic management of patients with Morquio-Brailsford syndrome is a challenge that is further increased by extending indications for surgical intervention to include infants. With respect to protecting the airway, fiberoptic nasotracheal intubation of the spontaneously breathing child is our method of choice. PMID- 8363035 TI - [Experience with the anesthesia pass]. PMID- 8363036 TI - [Regional anesthesia techniques and hemostasis disorders]. AB - Hereditary or acquired disorders of coagulation often lead to the question of whether it is permissible to perform regional anaesthetic techniques. Disorders of coagulation that cannot be treated are generally contraindications to regional anaesthesia. The history and clinical findings represent the most important measures before employing a regional anaesthetic technique. The use of anticoagulant agents as well as non-steroidal antirheumatics and acetylsalicylic acid should be determined. In addition to coagulation studies, the use of regional anaesthetic techniques during simultaneous anticoagulant treatment requires a clear arrangement with the operative department in question. In most instances there will be a tendency to perform general anaesthesia, however, considering the fact that general anaesthesia is also associated with complications (intratracheal bleeding), regional anaesthesia represents an alternative method, especially in patients with significant concomitant disorders. In this situation the possibility of peripheral nerve blockade should be taken into consideration. PMID- 8363037 TI - Immunohistochemical visualization of the enteric nervous system using antibodies against protein gene product (PGP) 9.5. AB - Both the investigation of the enteric nervous system and the diagnosis of its pathological changes require reliable staining methods. In order to assess the potential of protein gene product (PGP) 9.5 as a marker for the enteric nervous system, we examined its immunoreaction in whole-mount preparations of the guinea pig and porcine small intestine, using a rabbit polyclonal antiserum. The immunohistochemical technique reveals the fundamental architectural features of the ganglionic and aganglionic plexuses. Furthermore, it enables a reproducible and differentiated visualization of the enteric nerve cells to be made, so that the various nerve cell types can be morphologically identified. PMID- 8363038 TI - Lectin histochemical study of early postnatal vascularization of the developing pars distalis adenohypophysis of the gray short-tailed opossum (Monodelphis domestica, Marsupialia). AB - Individuals from 18 litters between 0.5 day and 13 days post partum, and two adult specimens of Monodelphis domestica (Marsupialia), were studied by TEM and lectin histochemistry. Positive reactions for PO-lectins in the developing pituitary were found in the vascular and/or perivascular elements; secretory cells did not react. Positive vascular reactions varied with both the type of lectin and the age of the developing animal. In the adults, the reactions were reversed: there were no vascular, but a variety of positive cellular reactions. It is concluded that the adenohypophyseal blood vascular system is very far from being complete and mature in the newborn M. domestica. According to specific data taken from the literature, the lectin histochemistry indicates a sequential appearance of several components of the extracellular matrix, suggesting also that the actively organ-invading capillaries may be a good model for the study of basement membrane development. PMID- 8363039 TI - Ultrastructural and morphometric studies on the peripheral course of the vagus in the domestic fowl, with particular reference to the cholinergic innervation of the pancreas. AB - Cytochemical and morphometric studies were carried out to ascertain the peripheral course of the vagus nerve to the chicken pancreas. Nerve bundles accompanying the left gastric artery were named tentatively the left gastric artery nerve which contained unmyelinated and myelinated nerve fibers showing the acetylcholinesterase positive reaction. After vagotomy various degenerating features were observed in both the unmyelinated and myelinated nerve fibers of the left gastric artery nerve. The ratio of unmyelinated nerve fibers to myelinated nerve fibers decreased significantly following vagotomy, whereas there was no significant difference in the total number of myelinated nerve fibers between the control and vagotomized chickens. Thus, it is hypothesized that the total number of unmyelinated nerve fibers decreases significantly following vagotomy. Our studies yielded the evidence that the left gastric artery nerve contains the unmyelinated nerve fibers derived from the vagus nerve. Moreover, the coeliac plexus showed no significant change in the ratio of unmyelinated to myelinated nerve fibers nor signs of degeneration following vagotomy, although both were observed in the nerve bundles accompanying the pancreatico-duodenal artery. It is, therefore, concluded that a peripheral branch of the vagus nerve runs together with the left gastric and the pancreatico-duodenal arteries, and must innervate the pancreas as the preganglionic nerve fiber. PMID- 8363040 TI - [C-cells in the thyroid gland and in the remainder of the ultimobranchial body of bison]. AB - C cells of the thyroid gland of 85 European bison, 43 males and 42 females, of age ranging from 1 month to 25 years were examined. For the identification of the C cells by Grimelius silver impregnation, toluidine blue, pseudoisocyanin and azur A stainings were employed. In the thyroid of the bison the C cells in the central region were distributed denser than in the peripheral region. They may particularly appear in great numbers in the interior of ultimobranchial (UB) remnants; in these cases, however, a great variety of changes has been observed. In part of the adults animals individual differences of the hyperplasia C cells in the preserved UB structures were observed: C cells have not been detected in the internal parathyroid glands. In the discussion, the meaning of paracrine has been described in autoregulatory mechanisms controlling the thyroid activity. PMID- 8363041 TI - [The vascular system of the intestines of Gallus domesticus]. AB - The vascular system of the chicken intestine was investigated by corrosion cast, light and electron microscopic methods. In the intestinal villi the "Fontainentyp" is present with a single arteriole rising to the apex and draining into subepithelial capillaries. Occasionally ramifications of the arteriole occur in the upper third of the villi. Another variation is splitting of the arteriole into a capillary net at the base of the villi in the caeca between the regions with and without villi. At the tip, at the margins and at the base of the villi the capillaries fuse into venules, which proceed to the inside and empty into veins. At the base above the propria they form a superficial net with connecting veins arising to an inferior venous plexus below the region of crypts. The submucosal collecting veins descend from short vascular truncs, which originate from the inferior plexus and cross the muscularis mucosae. Elements of a vasoregulatory system like arterio-venous marginal loops, submucosal arterio venous anastomoses, sphincter-arteries, precapillary sphincters and sphincter veins well known in the literature are not found in the intestine of the domestic chicken. Therefore arterioles, capillaries and muscle bundles concentric around the veins in the villi seem to take over this function. PMID- 8363042 TI - Fibrous trabeculae in the liver of alligator (alligator mississippiensis). AB - In the mature alligator, fibrous trabeculae run from the portal areas and capsule through the hepatic parenchyma. The extent of these trabeculae becomes clear only after staining for collagen with, for example, Fast green or Picrosirius red. The trabeculae are less well developed in young caiman. The alligator's liver might use the trabeculae to withstand thrashing of the body. PMID- 8363043 TI - Craniofacial angle in dolicho-, meso- and brachycephalic dogs: radiological determination and application. AB - Observations on craniofacial axes and angles were made on fifty dogs belonging to five breeds, by means of radiological techniques (lateral radiographs) and biostatistical methods. The craniofacial angles were found to be 25-26 degrees (greyhound), 19-20 degrees (pointer), 20-21 degrees (German shepherd), 13-14 degrees (boxer) and 9-10 degrees (Pekinese). Shortening of the head in brachycephalic dogs implies a more perpendicular development of the cranium relative to the facial axis. The possible application of these data in the determination of morphological types in many fields is discussed. PMID- 8363044 TI - [Ontogeny of the human temporomandibular joint]. AB - An analysis of the human temporomandibular joint is done regarding to the appearance of secondary cartilage formations during the prenatal development of condylus and temporal joint elements. Sagittal sections of nine human fetuses (49 mm CRL to 315 mm CRL) show a closed relationship between the development of the bony and soft tissues of the joint. The temporary appearance of secondary cartilage in the temporal joint area is induced by the functional loading of the capitulum. This process requires the genesis of the two free articular cavities on the one side and the functional attachment of the lateral pterygoid muscle to the discus and the collum mandibulae on the other. Pointing out the clear relationship of the articulating joint surfaces and the in between discuss, a left temporomandibular joint of a fetus (125 mm CRL) is reconstructed in a medioventral view with the help of a three dimensional drawing. The location of the temporal secondary cartilage formation within the centre of the temporal loading area of the condyle assures its functional genesis during the embryological development of the human temporomandibular joint. PMID- 8363045 TI - Morphological classification of the masticatory muscles in dogs based on their innervation. AB - The masticatory muscles and their innervations in dogs are classified, from deep to superficial layers, as follows: 1) medial pterygoid muscle and medial pterygoid nerve, 2) lateral pterygoid muscle and lateral pterygoid nerve, 3) anterior deep part of temporal muscle and anterior deep temporal nerve, 4) posterior deep part of temporal muscle and posterior deep temporal nerve, 5) superficial part of temporal muscle and superficial temporal nerve, the only branch of the temporal nerve which passes out from the infratemporal fossa, 6) zygomaticomandibular part of masseter muscle, which is thought to belong to the masseter muscle, and masseter nerve, 7) deep layer of masseter muscle and masseter nerve, 8) superficial layer of masseter muscle and masseter nerve. PMID- 8363046 TI - Clinical anatomy of the subcutaneous veins in the dorsum of the hand. AB - Ninety adult upper extremities from human cadavers were used to study the patterns of the subcutaneous veins in the dorsum of the hand, with careful dissection and measurement under magnification. In our series, the distribution of the veins was not symmetrical in the dorsum of the hand. In 83.3% of the cases, the veins were arranged in two groups, radial and ulnar, above the transverse midline of the dorsum. The area between these two groups, corresponding to the proximal halves of the second metacarpal bone, the second intermetacarpal space and the third metacarpal bone, might be called "vein lacking area". Crossing branches of veins were found in all cases. There were on average three crossing branches in each case, and their internal diameters were 0.9 +/- 0.2 mm. This study established that the subcutaneous veins in the dorsum of the hand are arranged in two layers. They communicate freely with the veins in the palmar aspect through the intermetacarpal spaces. The average number of perforating branches was 3.9, and their internal diameters were 1.0 +/- 0.4 mm. The perforating branch in the first intermetacarpal space was wide (internal diameter: 1.8 +/- 0.3 mm) and very constant (appearance rate: 100%). This branch may be the most important communication between the superficial and deep veins. We found the venous values in 70.0% of the perforating branches, which prevent the blood flowing from the dorsum to the palm. PMID- 8363047 TI - One hundred years of anthropological studies in Bulgaria. AB - The anthropological studies are divided into three distinct periods: initial- covering the last decades of the 19th century, classical--mirroring the results of studies carried out in the first half of the 20th century, and contemporary- marked by the organization of the Section of Anthropology and Human Anatomy in the Institute of Morphology at the Bulgarian Academy of Sciences (actually the Institute of Cell Biology and Morphology) in 1953, and by the research done during the second half of the current century. The roles and contributions of Dr. Jonas Basanovichjus, Prof. Stefan Vatev, D. Sc., Dr. Krum Dronchilov, Prof. Milko Balan, D. Sc., Prof. Dimitar Kadanov, D. Sc. and others to the development of Bulgarian anthropology is underscored. PMID- 8363048 TI - Long-term osteopenic changes in cancellous bone structure in ovariectomized rats. AB - Cancellous bone mass decreases following ovariectomy in rodents, providing a useful model for post-menopausal bone loss in humans. This study describes and quantifies the longer-term changes in cancellous bone structure in the ovariectomized (OVX) rat. Rats were OVX or sham-OVX at 100 days of age and bones were collected 540 days later. Lumbar vertebral bodies were prepared for microradiography and structural analyses (nodal analyses and star volume analyses) of cancellous bone. Proximal humerii were prepared for scanning electron microscopy (SEM). Microradiography confirmed the loss of cancellous bone from the central spongiosa regions of the vertebral bodies and the humerii in the OVX rats. Changes in trabecular structural elements included relative increases in the number of free to free, cortical to free, cortical to node struts and decreases in the node to node struts in the OVX animals compared with controls. There were increases in average lengths of the node to free, node to node, and free to free trabecular struts in the OVX animals. The marrow star volume was increased in the OVX animals indicating a greater trabecular separation in these animals compared with controls. Viewed by SEM, metaphyseal trabeculae in the controls consisted of rods and plates but in the OVX animals the remaining trabeculae were mostly longitudinal rods with smaller transverse connecting rods. The remaining bone in the OVX animals was found in the lateral metaphyseal areas and is consistent with maintenance of the structural capacity of the bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363049 TI - Ultrastructural localization of a nuclear autoantigenic sperm protein in spermatogenic cells and spermatozoa. AB - This study demonstrates the ultrastructural localization of rabbit nuclear autoantigenic sperm protein (NASP) in spermatogenic cells and spermatozoa. NASP is present in rabbits, rats, mice, and human testes and spermatozoa. It has recently been sequenced in rabbits and humans and characterized as an acidic, histone binding protein. Currently it has been proposed that NASP may play a role in regulating early events of spermatogenesis through its ability to bind and translocate testicular histone variants to nucleosomes. The ultrastructural localization of NASP confirms that it is initially present in primary spermatocytes in their Golgi regions and nucleus. In round spermatids it is present in the nucleus as well as in the acrosome and subacrosomal space. In later spermatids, testicular spermatozoa, and ejaculated spermatozoa, NASP is concentrated over the nucleus, although some is still present in the acrosome. It is likely that NASP would be carried into the ovum with the sperm nucleus at fertilization. PMID- 8363050 TI - Ultrastructure and morphometry of the urethral glands in normal, castrated, and testosterone-treated castrated male mice. AB - Recent studies of the urethral glands in the male mouse and rat have suggested that they are testosterone-dependent glands that may be potential sites for secretory immunity in the male genital tract. In the present study we describe the ultrastructural features of these glands in normal mice and provide quantitative data on the sizes of the acinar cells and their organelles in sham-, oil-, and testosterone-treated castrated mice. Acinar cells in urethral glands from normal mice contain numerous secretory granules, prominent Golgi complexes, elongated mitochondria, and an abundance of rough endoplasmic reticulum (RER) with large and dilated cisternae, all of which are features characteristic of secretory cells. In some acinar cells the cisternae of the RER were filled with closely packed, unbranched, straight, tubular structures that were oriented parallel to one another, that radiated from aggregates of dense material, or that were randomly arranged. In other acinar cells the cisternae of the RER showed a network of branching and anastomosing vesicular-like structures whose limiting membranes were occasionally seen in continuity with the membranes of the RER. Secretory acini showed large, unbranched tubules in the acinar lumen. When cut at right angles the large tubules exhibited a distinct fuzzy outer coat with fine projections radiating outwards. The ultrastructure of the acinar cells and the presence of tubules in the lumen suggests that they are engaged in secretion of a tubular protein. Morphometric analysis of acinar cells in the urethral glands showed that the mean volumes of nuclei, cytoplasm, secretory granules, vacuoles, and mitochondria were significantly reduced in castrated mice in comparison to either normal or testosterone-treated castrated mice. This confirms earlier observations that the urethral glands are targets of testosterone. PMID- 8363051 TI - Seasonal changes of the blood-testis barrier in viscacha (Lagostomus maximus maximus): a freeze-fracture and lanthanum tracer study. AB - Adult male viscachas (Lagostomus maximus maximus) were gathered from their natural habitat during the period of complete spermatogenesis (June) and during the month of maximum testicular regression (August). The testes were processed by conventional electron microscopic technique using lanthanum nitrate (electron dense intercellular tracer) to define the intercellular spaces below the inter Sertoli tight junctions and by freeze-fracture techniques. During complete spermatogenesis the tracer surrounds spermatogonia, preleptotene, and leptotene spermatocytes and stops at the level of the inter-Sertoli tight junctions below all germ cells displaying synaptonemal complexes (zygotene-pachytene spermatocytes) and germ cells in more advanced stages of differentiation. Conversely, during testicular regression the tracer percolates all intercellular spaces between Sertoli cells and the remaining germ cells (spermatogonia and few preleptotene and leptotene spermatocytes). During complete spermatogenesis, freeze-fracture replicas exhibit numerous inter-Sertoli tight junction strands parallel to each other and to the basal lamina. During spermatogenesis decay, the inter-Sertoli tight junctions are found to be short, tortuous, frequently interrupted, and often associated with extented membranous areas of gap junctions. PMID- 8363052 TI - Apical excrescences in the gallbladder epithelium of the female Syrian hamster in response to medroxyprogesterone. AB - All the intact female Syrian hamsters treated with medroxyprogesterone (MP) for a one-month period, without dietary manipulation, display gallbladder surface epithelial changes, and intraluminal deposits. These changes include excrescences in various stages, bulging, and extrusion of material from the epithelial cells. The most striking scanning electron microscopic observations are the dramatic events, comparable to apocrine-like secretory events observed in another related study using oophorectomized hamsters. Since the hamster gallbladder does not possess mucous goblet cells, it appears that this phenomenon could be a response to the MP treatment, thus providing a larger amount of mucous product than usual with cellular material, in addition to the possible alteration in the quality of the bile following this treatment. As a result of MP treatment, intraluminal deposits were also confirmed by using light and transmission electron microscopy. In control hamsters these events were not observed, however, small blebs outlining surface epithelial cells are seen. The results in this report complement the previous studies using the male and oophorectomized Syrian hamster model subjected to similar experimental conditions. PMID- 8363053 TI - Localization of glycogen synthase activity in liver of fasted normal and adrenalectomized rats after injection of dexamethasone. AB - Hepatic glycogen synthase activity was localized in normal and adrenalectomized (ADX) rats after fasting overnight and in fasted ADX rats after injection of dexamethasone (DEX) 2-8 h prior to sacrifice to stimulate glycogen synthesis. Cryostat sections were incubated in medium containing substrate to demonstrate glycogen synthase activity as indicated by glycogen synthesized during incubation. Sections from fasted normal rats showed limited dispersed glycogen synthase activity in both periportal and centrilobular regions. In contrast, activity for glycogen synthase in hepatocytes from fasted ADX rats appeared as large aggregates in random hepatocytes throughout the lobule. Two hours after injection of DEX the reaction product appeared as aggregates in some hepatocytes, but other cells revealed dispersed enzyme activity. Glycogen synthase activity was evident in more hepatocytes after 4 h treatment with DEX and after 8 h virtually all hepatocytes contained abundant reaction product. The results suggest that synthase activity becomes concentrated in limited regions of selected hepatocytes in fasted ADX rats. DEX stimulation of glycogen synthesis for 4-8 h results in increased enzyme activity. PMID- 8363054 TI - Cardiac conduction system in the chicken: gross anatomy plus light and electron microscopy. AB - Twenty-three chicken hearts were used to study the cardiac conduction system by light and electron microscopy. In addition to a sinus node, atrioventricular node (AVN), His bundle, left and right bundle branches (LBB, RBB), the chicken also has an AV Purkinje ring and a special middle bundle branch (MBB). The sinus node lies near the base of the lower portion of the right sinoatrial valve. The AV node is just above the tricuspid valve and anterior to the coronary sinus. The His bundle descends from the anterior and inferior margin of the AV node into the interventricular septum, then dividing into right, left and middle branches some distance below the septal crest. The middle bundle branch turns posteriorly toward the root of the aorta. The AV Purkinje ring originates from the proximal AV node and then encircles the right AV orifice, joining the MBB to form a figure of-eight loop. The chicken conduction system contains four types of myocytes: 1) The P cell is small and rounded, with a relatively large nucleus and sparse myofibrils. 2) The transitional cell is slender and full of myofibrils. 3) The Purkinje-like cell resembles the typical Purkinje cell, but is smaller and darker. 4) The Purkinje cell is found in the His bundle, its branches, and the periarterial and subendocardial Purkinje network. PMID- 8363055 TI - Expression and accumulation of interstitial collagen in the neonatal rat heart. AB - Significant physiological changes occur in the heart following birth including increased arterial blood pressure and heart rate. Concurrently, biochemical and structural alterations are evident in the neonatal heart in response to these dynamic physiological properties. Prominent among these is the elaborate development of the cardiac extracellular matrix, composed primarily of interstitial collagen. The collagenous fibers, together with other matrix components, form an elastic, stress-tolerant network which functions in the dissipation of force throughout the heart wall. The present studies have used biochemical and molecular techniques to show the temporal and spatial patterns of interstitial collagen accumulation and expression during late fetal and neonatal development of the rat heart. The use of biochemical and particularly molecular methodologies allows the analysis of the expression of matrix components at a resolution previously not attained by structural studies alone. These data show relative increases in interstitial collagen immediately following birth as well as spatial differences in collagen mRNAs within the heart. The data presented provide further evidence for a role of mechanical stimulation in the regulation of collagen gene expression during this period of heart development. PMID- 8363056 TI - Vascularization of the pineal complex in the lizard Tiliqua rugosa. AB - The vascularization of the pineal complex in the lizard Tiliqua rugosa was investigated by vascular corrosion and latex casting techniques. The fine structure of the pineal capillaries was also studied by transmission electron microscopy. The pineal complex in T. rugosa consists of an elongated pineal gland proper and a separate, distinct parietal eye. The pineal complex derives an abundant blood supply from branches of the middle and posterior cerebral arteries. Scanning electron microscopy of vascular corrosion casts revealed a dense and extensive pineal capillary bed which drains ultimately into a wide longitudinal sinus suggesting an efficient pathway for the rapid removal of substances secreted by the gland. The parietal eye, which receives a unilateral left-sided blood supply from the unpaired anterior pineal artery, is shown to be a highly vascularized structure. The close morphological relationship between the pineal gland and dorsal sac, where the two structures apparently share the same blood vessels, suggests a functional relationship between them. The pineal capillaries are fenestrated with tight junctions between adjoining endothelial cells. Podia-like abluminal extensions of the endothelial cells were observed in close relation to unmyelinated nerve bundles. The basal margin of the pineal parenchyma is highly invaginated with thin finger-like cytoplasmic protrusions into the pericapillary space. Distinct bands of microfibrils form "struts" anchoring the pineal parenchyma to the endothelial wall. These features may have a role in the transfer of materials between the pineal gland and the blood stream. PMID- 8363057 TI - Prolactin alters the expression of integumental glycoconjugates in the red spotted newt, Notophthalmus viridescens. AB - Prolactin (PRL)-mediated changes in the texture and secretory activity of the skin in adult red-spotted newts may involve alterations in the distribution and/or expression of structural and secretory epidermal glycoconjugates. To explore this possibility, skin samples were obtained from groups of conditioned animals that had received injections of either ovine prolactin or amphibian saline over a 14-day period. Glycoconjugates within the epidermis and cutaneous glands were examined by means of lectin histochemistry using a panel of eight HRP labelled lectins. PRL increased levels of sialic acid and n-acetylglucosamine in the stratum corneum. In contrast, glycoconjugates containing fucose, galactose, n acetylgalactosamine, and galactose-(1,3)-n-acetylgalactosamine were decreased by PRL within both glands and epidermis. These results suggest that the integumental effects associated with prolactin in the red-spotted newt are mediated, at least in part, through the alteration of epidermal and glandular glycoconjugates. PMID- 8363058 TI - Ultrastructural characteristics of primordial germ cells in the quail embryo. AB - An avian species, the quail has become a desirable animal model in experimental embryology and reproductive biology. To understand the ultrastructural characteristics of primordial germ cells (PGC) of this species, we studied PGC in the Japanese quail (Coturnix coturnix japonica) embryo at various developmental stages from their appearance in the germinal crescent through migration to settlement in the gonadal ridges by means of electron microscopy. The results were compared with those of another well-known avian species, the chick. Several ultrastructural characteristics of quail PGC not described previously in chick PGC were observed as follows: 1) No glycogen particles were detected in the cytoplasm at any stage examined. 2) Electron-dense and membrane-bounded granules were found in the PGC cytoplasm during the sexually indifferent gonadal stages. 3) Quail PGC were characterized by a prominent nucleolus associated with condensed chromatin (heterochromatin), and the developmental changes of the nucleus were noted; the nucleolus initially appeared as a compact mass at the germinal crescent stage and became dispersed at later stages during the colonization of the gonadal ridges. These findings suggest several physiological and functional differences in the cell cycle between these two avian species. This is the first report describing detailed ultrastructural characteristics of PGC in the quail embryo. PMID- 8363059 TI - Development of innervation of skeletal muscle fibers in man: relation to acetylcholine receptors. AB - The aim of this study was to establish the time scale of developmental changes in innervation of skeletal muscle fibers in man. Specimens of thigh and intercostal muscle from 19 embryos and 18 infants were examined with histological methods which enabled the discrimination between fetal (gamma) and adult (epsilon) types of acetylcholine receptors (AChRs). At 8 weeks of development, AChRs were distributed diffusely in the myotube membranes. Following onset of innervation in approximately the ninth week the length of the AChR positive area diminished and reached its shortest size at the sixteenth developmental week. At the sixteenth and eighteenth week some nerve terminals opposed the muscle membrane outside the AChR positive area. Decrease in the number of nerve terminals, strongly suggesting elimination of polyneuronal innervation, started in the sixteenth week and was completed in the twenty-fifth week. This fetal (gamma) type of AChR could no longer be demonstrated after the thirty-first week. The length of the end plates as determined by the presence of AChRs increased again in the last week before birth and reached a plateau size by the end of the first year after birth. It is concluded that in man the transition from poly- to mononeuronal innervation takes place between the sixteenth and twenty-fifth weeks of development. The evidence available suggests that the retraction of nerve terminals is preceded by loss of AChRs from the muscle membrane facing the terminals. There is no relationship between retraction of nerve terminals and the switch from fetal to adult type of AChR. The size of the presynaptic apparatus changes little after the first year of life. PMID- 8363060 TI - Effects of maternal bilateral ureteral ligation on fetal development of kidney in rats: morphometrical changes in glomerular components. AB - Development of the glomerulus in fetal kidney was studied morphometrically following ligation of both ureters of pregnant rats. The ligation was performed on days 17, 19, and 21 of gestation, and autopsy was done 24 hr after each operation. The percentage volumes of the five glomerular components (epithelial cells, capillary, mesangium, glomerular basement membrane, and Bowman's space) were determined by point counting, and the surface area of glomerular basement membrane per unit volume of glomerulus was calculated by intercept counting. On fetal days 18, 20, and 22, percentage volume of Bowman's space in the fetuses from the ligated mothers was significantly smaller than that in the fetuses from sham-ligated mothers. On fetal days 20 and 22, surface area of glomerular basement membrane and glomerular capillary length per unit volume of glomerulus and percentage of glomerular capillary volume in the fetuses from the ligated mothers were significantly larger than those in the fetuses from sham-ligated mothers. These results suggest that maternal bilateral ureteral ligation induces an increase in filtration area of glomerulus in fetal kidney when the fetal kidney is functional. PMID- 8363061 TI - Histogenetic potential of rat hind-limb interdigital tissues prior to and during the onset of programmed cell death. AB - The histogenetic potential of interdigital tissues isolated from the autopod of rat embryonic hind-limbs between 14.5 and 16.5 days was investigated. A wedge of tissue containing ectoderm and mesoderm was excised from between the developing digits and grafted beneath the kidney capsule of adult rats for two weeks. We have previously demonstrated that the renal capsule is an excellent site for permitting limb tissues to proliferate and differentiate (Chan et al.: J. Exp. Zool., 260:74-83, 1991). At 14.5 days, when cell death (revealed with neutral red stains) within the interdigital zone was limited to the apical ectodermal ridge (AER), the interdigital mesoderm was capable of developing into bone, cartilage, and loose connective tissue in the kidney. It was estimated that the skeletal elements occupied approximately 38% of the overall area of the grafts. In addition, the ectoderm was able to produce keratinized epithelium, hair follicles, and sebaceous glands. In 15.5 day autopod, necrosis was present both in the AER and the mesoderm between the AER and marginal sinus. Interdigital mesoderm obtained from this stage of development formed cartilage but not as extensively as that derived from 14.5 day autopod (4% as compared with 38%). Necrotic cells were present in all of the interdigital zones at 16.5 days. Ten explants were introduced into the kidney at this stage, but only 4 grafts were recovered after 2 weeks. In all cases, the explants did not produce cartilage. Only a small amount of keratinized epithelium and loose connective tissue was found. In summary the interdigital mesoderm has the potential to develop bone, cartilage, and loose connective tissue, but this ability is progressively lost during morphogenesis. PMID- 8363062 TI - Quantitative ultrastructural analysis of the periaqueductal gray in the rabbit. AB - The fine structure of the periaqueductal gray (PAG) of the rabbit was examined using the transmission electron microscope. On the basis of synaptic polarity, vesicle size, and the nature of the pre- and post-synaptic elements, 10 essentially different synaptic types could be discerned (6 axo-dendritic, 2 axo somatic, 1 axo-axonic, and 1 dendro-dendritic). Synaptic contacts on the soma of PAG neurons were small and covered, on average, only 1.6% of the soma surface. The most striking feature of the synaptic structure of the PAG was that more than 94.1% of all synapses were axo-dendritic. Of these, 83.5% were of the symmetrical type. Most of these contacts occurred on buttons of small to medium size, and contained either round vesicles of medium size or pleomorphic vesicles of medium size. Boutons containing only flattened vesicles were quite rare. Boutons contacting larger dendrites were generally small-to-medium in size, made asymmetric-type synaptic contacts, and contained pleomorphic vesicles of medium to-large size. Medium-sized dendrites were contacted principally by small boutons exhibiting either symmetrical or asymmetrical junctions containing medium-sized pleomorphic vesicles, and in addition a few of these boutons contained both large, and small, round vesicles. Dendritic spines were generally provided with only one synaptic contact, stretching the entire width of the spinous process. Boutons and the spines on dendrites were approximately the same size. Synapses between two vesicle-containing structures (axo-axonic or dendro-dendritic synapses) were rare (1.4%). They were generally asymmetric and contained round vesicles of medium size. Complex synapses, where a glial sheet enclosed the synapse, were occasionally observed. Also seen were multiple synapses, with up to 11 contacts on a single dendritic profile. Large dense-core vesicle were seen in approximately 40% of all synapses, whereas small dense-core vesicles were only found in about 3%. Data is provided on how different synaptic features relate to ventral, lateral, dorsal, and medial PAG. Principally this is in relation to neuron size, glia cell content, axonal characterization, and vesicular type. PMID- 8363063 TI - Incidence and histology of human accessory parotid glands. AB - The parotid glands of 228 Japanese human cadavers were examined to determine the incidence and histological features of accessory parotid glands. The incidence was found to be 56% with no differences between right and left sides or between sexes. Thirty parotid glands and their associated accessory glands were examined histologically: eight of these accessory glands were found to be mixed secretory glands (i.e., containing both serous and mucous acini). Thus, the pattern of differentiation of a significant fraction of accessory glands differs from that of the main parotid gland: it appears that mixed acini, present in the early stages of development, persist into later life, and their presence may be related to tumors developing at these sites. PMID- 8363064 TI - General versus regional anesthesia for peripheral vascular surgery. Is the problem solved? PMID- 8363065 TI - Sympathetic nervous system activation and hyperdynamic circulation associated with desflurane: not all isomers are created equal. PMID- 8363066 TI - Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Perioperative Ischemia Randomized Anesthesia Trial Study Group. AB - BACKGROUND: Perioperative morbidity may be modifiable in high risk patients by the anesthesiologist's choice of either regional or general anesthesia. This clinical trial compared outcomes between epidural (EA) and general (GA) anesthesia/analgesia regimens in a group of patients at high risk for cardiac and other morbidity who were undergoing similarly stressful surgical procedures. METHODS: One hundred patients scheduled for elective vascular reconstruction of the lower extremities were randomized to receive either EA for surgery followed by epidural analgesia, or GA for surgery followed by intravenous patient controlled analgesia. Hemodynamic monitoring, blood pressure, and heart rate limits were determined prior to randomization. Management of anesthesia in the immediate postoperative period was standardized. The data collected included continuous electrocardiographic monitoring from the day before surgery through the third postoperative day, serial electrocardiograms, and cardiac enzymes. Cardiac ischemia, myocardial infarction, unstable angina, and cardiac death were identified by a cardiologist blinded to the type of anesthesia received. Other major morbidity was determined at the time of hospital discharge and at 1 and 6 months after surgery. RESULTS: Eleven patients who received GA required regrafting or an embolectomy during their hospital stay, compared with two patients who received EA. This association of GA with reoperation remained significant after adjustment for baseline differences. Cardiac outcomes were similar in the two groups with respect to perioperative death (1 EA and 1 GA), death within 6 months (4 EA and 3 GA), nonfatal myocardial infarction within 7 days (2 EA and 2 GA), unstable angina (0 EA and 2 GA), and myocardial ischemia following randomization (17 EA and 23 GA). Rates of major infections in the two groups (1 EA and 2 GA), renal failure (3 EA and 3 GA), and pulmonary complications (3 EA and 7 GA) also were similar. CONCLUSIONS: Carefully conducted epidural and general anesthesia appear to be associated with comparable rates of cardiac and most other morbidity in patients undergoing lower extremity vascular surgery. However, compared with general anesthesia, epidural anesthesia is associated with a lower incidence of reoperation for inadequate tissue perfusion and, therefore, may be advantageous for this surgical population. PMID- 8363067 TI - The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Perioperative Ischemia Randomized Anesthesia Trial Study Group. AB - BACKGROUND: The purpose of this clinical trial was to compare the effects of different anesthetic and analgesic regimens on hemostatic function and postoperative arterial thrombotic complications. METHODS: Ninety-five patients scheduled for elective lower extremity vascular reconstruction were randomized to receive either epidural anesthesia followed by epidural fentanyl (RA) or general anesthesia followed by intravenous morphine (GA). Intraoperative and postoperative care were controlled by protocol using predetermined limits for heart rate, blood pressure, and other monitoring criteria. Data collection included serial physical examinations, electrocardiograms, and cardiac isoenzymes to detect arterial thrombosis (defined as unstable angina, myocardial infarction, or vascular graft occlusion requiring reoperation). Fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer levels were measured preoperatively and at 24 and 72 h postoperatively. RESULTS: Preoperative fibrinogen levels were similar in both groups, remained unchanged after 24 h, and increased equally (45%) in the first 72 h postoperatively. PAI-1 levels in the GA group increased from 13.6 +/- 2.1 activity units (AU)/ml to 20.2 +/- 2.6 AU/ml at 24 h and returned to baseline at 72 h. In contrast, PAI-1 levels in the RA group remained unchanged over time. Twenty-two of 95 patients (23%) had postoperative arterial thrombosis, 17 of whom had received GA and 5 of whom, RA. Preoperative PAI-1 levels were higher in patients who developed postoperative arterial thrombosis (20.5 +/- 3.6 AU/ml vs. 11.2 +/- 1.4 AU/ml). Multiple logistic regression analysis indicated that GA and preoperative PAI-1 levels were predictive of postoperative arterial thrombotic complications. CONCLUSIONS: Impaired fibrinolysis may be related causally to postoperative arterial thrombosis. Because RA combined with epidural fentanyl analgesia appears to prevent postoperative inhibition of fibrinolysis, this form of perioperative management may decrease the risk of arterial thrombotic complications in patients undergoing lower extremity revascularization. PMID- 8363068 TI - Sympathetic hyperactivity during desflurane anesthesia in healthy volunteers. A comparison with isoflurane. AB - BACKGROUND: Desflurane has been reported to produce more tachycardia and hypertension on induction than isoflurane. The present study employed microneurography to determine whether these cardiovascular effects were related to sympathetic outflow. METHODS: In 14 healthy, young (age 20-31 yr) volunteers, arterial pressure was measured from the radial artery, forearm blood flow was derived by strain gauge plethysmography, and sympathetic nerve activity (SNA) directed to skeletal muscle blood vessels was recorded from a tungsten needle placed percutaneously into the peroneal nerve. Heart rate, blood pressure, muscle SNA, respiration, tidal volume, end-tidal carbon dioxide, and desflurane or isoflurane concentrations (infrared spectroscopy) were continuously monitored before and during anesthesia. Two minutes after administering thiopental (5 mg/kg) and vecuronium (0.2 mg/kg), desflurane (n = 7) or isoflurane (n = 7) was titrated gradually to the inspired gas over several minutes to 1.5 MAC. RESULTS: The initiation of desflurane anesthesia resulted in significant changes that included a 2.5-fold increase in SNA, hypertension (peak mean arterial pressure 114 +/- 3 mmHg), tachycardia (peak heart rate 102 +/- 6 beats/min), facial flushing, and tearing. Moderate upper airway obstruction developed in three subjects approximately 4 min after initiating desflurane, despite neuromuscular blockade. These responses were not observed in subjects receiving isoflurane. After tracheal intubation, the anesthetic concentration was maintained at 0.5 MAC for 30 min. Steady-state measurements of hemodynamics and SNA were obtained. Similar steady-state measurements were obtained 15 min after establishing 1.0 and 1.5 MAC. Both anesthetics produced a progressive reduction in blood pressure and forearm vascular resistance, and muscle SNA gradually increased. In subjects receiving desflurane, heart rate remained unchanged until the 1.5-MAC level was reached, at which time tachycardia (a 10-beat/min increase) was noted. The transition from 1.0 to 1.5 MAC desflurane resulted in significant heart rate increases (> 30 beats/min), hypertension (> 30 mmHg), and a doubling of SNA that persisted for several minutes. These responses did not occur in the isoflurane group. CONCLUSIONS: Titration of desflurane following thiopental induction and increasing the concentration of desflurane from 1.0 to 1.5 MAC result in sympatho excitation, hypertension and tachycardia in healthy, young volunteers. Until methods are determined to attenuate these responses, desflurane should be administered with great caution to patients who may be placed at risk by these responses. PMID- 8363069 TI - Awareness and recall during general anesthesia. Facts and feelings. AB - BACKGROUND: Experiences of awareness and recall during general anesthesia can be most distressing for patients. To obtain relevant information, the authors systematically interviewed patients in whom awareness during surgery had occurred, and questioned them about their experiences. METHODS: Twenty-six patients, referred by colleagues, described the facts and feelings they had experienced during the period of awareness, and whether these had had any consequences. Available anesthetic records were independently judged by three experienced anesthesiologists for relevant parameters. RESULTS: Auditory perception and the sensation of paralysis were most frequently mentioned, followed by the sensation of pain. Patients' feelings were mostly related to anxiety, panic, powerlessness, and helplessness. Eighteen patients (70%) experienced unpleasant aftereffects, including sleep disturbances, dreams and nightmares, and flashbacks and anxiety during the day. Only nine patients (35%) had informed their anesthesiologists about what had taken place. Twelve anesthetic records were assessed. In three, the occurrence of awareness had been indicated, while, in a fourth, it was noted that an amnesic drug had been given at a moment of increased blood pressure. Experienced anesthesiologists were unable to reliably distinguish awareness cases from matched controls when judging the records. CONCLUSIONS: Details recalled from the period of awareness correspond with data from the literature. The anesthesiologist's role in discussing, and dealing with, traumatic experiences related to anesthesia may be of great importance. The hand-written anesthetic record is of limited value in retrospectively explaining why awareness and recall have occurred. PMID- 8363070 TI - The threshold for thermoregulatory vasoconstriction during nitrous oxide/isoflurane anesthesia is lower in elderly than in young patients. AB - BACKGROUND: Thermoregulatory vasoconstriction minimizes further core hypothermia during anesthesia. Elderly patients become more hypothermic during surgery than do younger patients, and take longer to rewarm postoperatively. These data indicate that perianesthetic thermoregulatory responses may be especially impaired in the elderly. Accordingly, the authors tested the hypothesis that the thermoregulatory threshold for vasoconstriction during nitrous oxide/isoflurane anesthesia is reduced more in elderly than in young patients. METHODS: The authors studied 12 young patients aged 30-50 yr and 12 elderly patients aged 60 80 yr. All were undergoing major orthopedic or open abdominal surgery. Anesthesia was induced with thiopental and fentanyl, and maintained only with nitrous oxide (70%) and isoflurane (0.6-0.8%). Core temperature was measured in the distal esophagus. Fingertip vasoconstriction was evaluated using forearm minus fingertip, skin-temperature gradients. A gradient of 4 degrees C identified significant vasoconstriction, and the core temperature triggering vasoconstriction identified the thermoregulatory threshold. RESULTS: The vasoconstriction threshold was significantly less in the elderly patients (33.9 +/- 0.6 degree C) than in the younger ones (35.1 +/- 0.3 degrees C) (P < 0.01). The gender distribution, weight, and height of the elderly and young patients did not differ significantly. The end-tidal isoflurane concentration at the time of vasoconstriction did not differ significantly in the two groups. CONCLUSIONS: These data indicate that thermoregulatory responses in the elderly are initiated at temperatures approximately 1.2 degrees C less than that in younger patients. Thus, it is likely that elderly surgical patients become more hypothermic than do younger patients, at least in part, because they fail to trigger protective thermoregulatory responses. PMID- 8363071 TI - Clonidine comparably decreases the thermoregulatory thresholds for vasoconstriction and shivering in humans. AB - BACKGROUND: Clonidine stops postoperative shivering, but its underlying mechanism of action is unknown. Clonidine may impair central control of thermoregulation or act on peripheral receptors. Accordingly, the authors tested the hypothesis that clonidine reduces both the vasoconstriction and shivering thresholds, a pattern consistent with central thermoregulatory impairment. METHODS: Seven healthy volunteers participated in the study. Thermoregulatory vasoconstriction was evaluated using forearm minus fingertip, skin-temperature gradients; values exceeding 4 degrees C were considered to be significant vasoconstriction. Systemic oxygen consumption (VO2) was measured with a canopy system. In addition, shivering was qualitatively evaluated using a simple scale, graduated from 0 (no shivering) to 2 (intense shivering). The tympanic membrane temperatures triggering significant vasoconstriction and grade 1 shivering were considered to be the thresholds for the two thermoregulatory responses. Measurements were performed after a 10-min steady state period and during cooling by central venous infusion of Ringer's lactate solution at 4 degrees C. Each subject was evaluated at two sessions, separated by at least 48 h. They were randomly and blindly assigned to received either an intravenous bolus of 75 micrograms clonidine or a placebo before cooling. When the shivering score equaled 2, 75 micrograms clonidine was injected intravenously, and repeated if necessary, to completely stop shivering. PMID- 8363072 TI - Postarthroscopy analgesia with intraarticular bupivacaine/morphine. A randomized clinical trial. AB - BACKGROUND: Postarthroscopy analgesia has been provided with intraarticular bupivacaine, but the duration of analgesia may be only a few hours. More recently, longer-lasting analgesia has been achieved using intraarticular morphine, although the onset of analgesia may be delayed. The combination of intraarticular morphine and bupivacaine has been suggested as an ideal analgesic after knee arthroscopy. METHODS: One hundred and twenty ASA Physical Status 1-2 outpatients, age 18-60 yr, having knee arthroscopy, were randomized into one of four treatment groups. Exclusion criteria included relevant drug allergy, extensive debridement or synovectomy, arthrotomy, postoperative intraarticular drainage, tracheal intubation, and patient refusal. All patients received general anesthesia with intravenous fentanyl, propofol, N2O, O2, and isoflurane. At the end of surgery, before tourniquet release, the following were injected intraarticularly through the arthroscope: group 1, 0.25% bupivacaine; group 2, 1 mg morphine in saline; group 3, 2 mg morphine in saline; and group 4, 1 mg morphine in 0.25% bupivacaine. The volume injected was 30 ml, and all solutions contained 1:200,000 epinephrine. Postoperative analgesia was provided with intravenous fentanyl and/or oral acetaminophen/codeine, and was recorded for 24 h. Visual analog pain scale (VAPS) scores and the McGill Pain Questionnaire (MPQ) were performed hourly from 1-6 h, and at 24 h postoperatively. RESULTS: Visual analog pain scale and MPQ scores were lowest in groups 1 and 4 at 1-6 h, but at 24 h, VAPS scores were lowest in groups 2, 3, and 4. Analgesic requirements were lower for the first 12 h in groups 1 and 4, but no difference was seen between groups over the 24-h study period. No adverse effects were noted. CONCLUSIONS: Morphine, 1 mg intraarticular, in 30 ml 0.25% bupivacaine, with 1:200,000 epinephrine, may provide superior postoperative analgesia for up to 24 h versus bupivacaine or morphine alone. PMID- 8363073 TI - Computer-controlled infusion of alfentanil for postoperative analgesia. A pharmacokinetic and pharmacodynamic evaluation. AB - BACKGROUND: Although computer-controlled infusion (CCI) of alfentanil has been shown to be effective intraoperatively, this technique has not been validated for postoperative use. Therefore, the authors examined the efficacy of this technique in providing postoperative pain relief. The study comprised both a validation of published pharmacokinetic data sets and the definition of the minimum effective analgesic concentrations after major orthopedic surgery. METHODS: The bias and inaccuracy of the implemented pharmacokinetic data set were examined, in 20 patients who had undergone major orthopedic surgery, by determination of the median performance error (MDPE) and median absolute performance error (MDAPE). The performance of two other published pharmacokinetic data sets was also examined by simulating the plasma concentrations that would have been predicted, had these data sets been implemented. The minimum effective analgesic concentrations (MEAC) were determined at the following time points: at the onset of pain, at 9:00 PM on the day of surgery, and at 9:00 AM and 9:00 PM on the first postoperative day. RESULTS: Measured plasma concentration-time profiles generally were parallel to the target concentration-time profiles. The MDPE and MDAPE obtained were 12% and 28%, respectively. The MEACs ranged from < 1 to 175 ng/ml and showed substantial interindividual variability. The median MEACs at the four study times were 59, 52, 65, and 43 ng/ml. The MEAC at 9:00 PM on the first postoperative day was significantly lower than those at the other study times (P < 0.05). CONCLUSION: Computer-controlled infusion of alfentanil provides adequate postoperative analgesia. The study demonstrated that pharmacokinetic data sets that are useful for intraoperative CCI of alfentanil are equally valid in the postoperative phase. Although required plasma concentrations of alfentanil are reasonably stable in time, interindividual variations are large, necessitating individual titration. PMID- 8363074 TI - Sufentanil increases intracranial pressure in patients with head trauma. AB - BACKGROUND: Sufentanil is an intravenous opioid often used as a component of anesthesia during neurosurgical procedures. However, the effects of sufentanil on intracranial pressure in patients with diminished intracranial compliance are not well established, and remain controversial. METHODS: Ten patients with head trauma, in each of whom the trachea was intubated, were studied for the effects of sufentanil on intracranial pressure (ICP) and on cerebral perfusion pressure (CPP). In all patients, ICP monitoring was instituted before the study. Sedation was obtained using a propofol infusion, and paralysis was achieved with vecuronium. After obtaining control of ICP (between 15 and 25 mmHg) hemodynamic values and blood gas tensions (PaCO2 between 30 and 35 mmHg), the level of sedation was deepened with an intravenous injection of sufentanil (1 microgram/kg over 6 min), followed by an infusion of 0.005 microgram.kg-1min-1. Mean arterial pressure (MAP), ICP (fiberoptic intracranial pressure monitor), and end-tidal CO2 were continuously measured and recorded at 1-min intervals throughout the 30-min study period. RESULTS: Sufentanil injection was associated with a statistically significant increase in ICP of 9 +/- 7 mmHg (+ 53%), which peaked at 5 min. Then ICP gradually decreased and returned to baseline after 15 min. This was accompanied by a significant decrease in MAP (24% decrease) and, thus, CPP (38% decrease). After 5 min, MAP and CPP gradually increased, but remained significantly decreased throughout the study. CONCLUSIONS: The results of the current study indicate that caution should be exercised in the administration of sufentanil bolus to patients with abnormal intracranial elastance, particularly if ICP is significantly increased. PMID- 8363075 TI - Desflurane and isoflurane have similar effects on cerebral blood flow in patients with intracranial mass lesions. AB - BACKGROUND: Before desflurane is advocated for patients undergoing neurosurgical procedures, it is necessary to determine the effect of desflurane on cerebral blood flow (CBF). In this study, CBF values are compared between desflurane and isoflurane at two doses. In addition, CBF reactivity to CO2 and the effect of prolonged exposure were compared between the two agents. METHODS: Cerebral blood flow measurements with intravenous 133Xe were performed in 24 patients undergoing craniotomy for mass lesions, randomized to receive either isoflurane or desflurane in oxygen and air. Cerebral blood flow was determined at 1 and 1.5 MAC concentrations at PaCO2 of 25 mmHg in the absence of surgical stimulation. Intraoperatively, with 1.25 MAC anesthesia, CBF was determined at target PaCO2 of 25 and 35 mmHg. In 15 patients, an additional measurement at 1.25 MAC was made before closure. RESULTS: At 1.0 MAC, mean +/- SD CBF values for the desflurane and isoflurane groups were 18 +/- 2 and 20 +/- 3 ml x 100 g-1 x min-1, respectively. At 1.5 MAC, CBF values were the same for the two anesthetics; 17 +/ 3 ml x 100 g-1 x min-1 for isoflurane and 19 +/- 4 ml.100 g-1 x min-1 for desflurane. During 1.25 MAC anesthesia, there were no differences between groups, with CO2 reactivity 1.3 +/- 1.2 ml x 100 g-1 x min-1 x mmHg-1 for desflurane and 1.6 +/- 0.6 ml.100 g-1 x min-1 x mmHg-1 for isoflurane. There was no demonstrable decrease in CBF with prolonged exposure to either agent. CONCLUSIONS: Desflurane and isoflurane are similar in terms of absolute CBF, the response to increasing doses, and the preservation of CO2 reactivity. PMID- 8363076 TI - Continuous calculation of intratracheal pressure in tracheally intubated patients. AB - BACKGROUND: Intratracheal pressure (Ptrach) should be the basis for analysis of lung mechanics. If measured at all, Ptrach is usually assessed by introducing a catheter into the trachea via the lumen of the endotracheal tube (ETT). The authors propose a computer-assisted method for calculating Ptrach on a point-by point basis by subtracting the flow-dependent pressure drop delta PETT(V) across the ETT from the airway pressure (P(aw)), continuously measured at the proximal end of the ETT. METHODS: The authors measured the pressure-flow relationship of adult endotracheal tubes with different diameters (ID, 7-9 mm) at different lengths and of tracheostomy tubes (ID, 8-10 mm) in the laboratory. The coefficients of an approximation equation were fitted to the measured pressure flow curves separately for inspiration and expiration. In 15 tracheally intubated patients under volume-controlled ventilation and spontaneous breathing, the calculated Ptrach was compared with the measured Ptrach. RESULTS: The authors present the coefficients of the "nonlinear approximation": delta PETT = K1.VK2, with delta PETT being the pressure drop across the ETT and K1 and K2 being the coefficients relating V to delta PETT. An important result was an inspiration/expiration asymmetry: the pressure drop caused by the inspiratory flow exceeds that of the expiratory flow. A complete description of the pressure flow relationship of an ETT, therefore, requires a set of four coefficients: K1I, K2I, K1E, and K2E. The reason for this asymmetry is the abrupt sectional change between ETT and trachea and the asymmetric shape of the swivel connector. Comparison of calculated and measured Ptrach in patients gives a correspondence within +/- 1 cmH2O (mean limits of agreement). The mean root-mean-square (rms) deviation is 0.55 cmH2O. CONCLUSIONS: Ptrach can be monitored by combining our ETT coefficients and the flow and airway pressure continuously measured at the proximal end of the ETT. PMID- 8363077 TI - Perioperative myocardial ischemia. Its relation to anatomic pattern of coronary artery stenosis. AB - BACKGROUND: Recently, the frequency of intraoperative myocardial ischemic episodes in patients with steal-prone coronary anatomy, compared with other groups of patients undergoing coronary artery surgery (CABG), has been characterized. Because the relationship between anatomic distribution of coronary stenosis and myocardial ischemic episodes over the entire perioperative period has not been well defined, the authors sought to examine this relationship in 100 adult patients undergoing CABG surgery. METHODS: Continuous electrocardiographic (ECG) monitoring was performed in the pre-, intra-, and postoperative periods, quantifying the frequency (episodes/hour of monitoring [epis/h]) and duration (minutes/hour of monitoring [min/h]) of ECG ischemic episodes defined as a reversible ST segment shift > or = 1 mm at J + 60 ms of > or = 1 min duration. Based on preoperative coronary angiography, patients were categorized into the following groups: group 1 (n = 40), steal-prone coronary anatomy (occluded major coronary artery and > or = 50% stenosis of left main coronary artery or > or = 70% proximal stenosis 2 (n = 17), left main or equivalent coronary stenosis (> or = 50% stenosis of left main coronary artery or > or = 70% proximal stenosis of the left anterior descending and circumflex coronary arteries); and group 3 (n = 43), coronary artery stenosis > or = 70% not fitting the preceding categories. RESULTS: Compared with group 3, patients in group 1 had more frequent and longer ECG ischemic events preoperatively, and were nearly two times more likely (relative risk 1.82, 95% confidence interval 1.07-3.10) to develop an ischemic event during this period. There were no differences in the relative risk, frequency, or duration of an ischemic episode between groups 1 and 3 during the intraoperative and postoperative periods, or between groups 1 and 2 or groups 2 and 3 during any perioperative period. In group 2 patients, the frequency of ischemic epis/h was less intra- compared with preoperatively, while, in group 3, the ischemic epis/h decreased postoperatively compared with the intraoperative period. The duration of ischemic episodes (min/h) in group 3, however, increased postoperatively compared with the pre- and intraoperative periods, while, in group 2, the duration of ischemic episodes (min/h) was less intraoperatively compared with the preoperative period. Ninety-seven percent of preoperative ECG ischemic episodes occurred without symptoms. Postoperative myocardial infarction occurred in three patients in group 3, two in group 2, and one in group 1. There were no perioperative deaths. CONCLUSION: These data indicate that, compared with patients with non-left main or equivalent coronary stenosis, those with steal prone coronary anatomy have more frequent and longer ECG ischemic episodes preoperatively. The data also indicate that there are no other differences in the risk, frequency, or duration of ischemic episodes between groups perioperatively. Thus, different distributions of coronary artery stenosis may be associated with changes in the perioperative characteristics of ECG ischemic episodes. PMID- 8363078 TI - Intravenous or epidural clonidine for intra- and postoperative analgesia. AB - BACKGROUND: Intravenous and epidural clonidine both produce postoperative analgesia. Several experimental reports demonstrate a spinal site of action for the analgesic effects of this alpha 2-adrenoceptor agonist. Therefore, the authors evaluated the clinical analgesic benefits of using clonidine, both intra- and postoperatively, by the epidural or the intravenous route. METHODS: Using a randomized prospective double-blind study design, 40 patients, between 18 and 50 yr of age, undergoing intestinal surgery under general propofol/nitrous oxide anesthesia, were enrolled. Before anesthesia, an epidural catheter was inserted at the L1-L2 interspace. At induction, a clonidine infusion was started at the doses of 4 micrograms/kg in 10 ml during 20 min, followed by 2 micrograms.kg-1 x h-1 (5 ml/h) during 12 h, either by the epidural (group 1) or by the intravenous (group 2) route. Intraoperatively, increased blood pressure and heart rate not responding to additional propofol bolus (0.5 mg/kg) was treated with a bolus of alfentanil (7 micrograms/kg). Postoperatively, morphine boluses (1.5 mg) were given through a PCA device according to the patient's need. Intraoperative analgesia was assessed by the alfentanil requirements. Postoperative analgesia was assessed by recording the morphine requirements, the visual analogue scale (VAS) at rest and after mobilization, and the patients' analgesia scale at 0, 3, 6, 12, 18, 24, and 36 postoperative hours. Sedation analogue scale and side effects were also recorded. Heart rate and blood pressure were particularly detailed during the first 2 h of the clonidine infusion. Plasma clonidine concentrations were measured after 20 min and 6, 12, and 24 h. RESULTS: Epidural clonidine significantly reduced the intraoperative alfentanil requirements (0.93 +/- 1.2 in group 1 vs. 2.4 +/- 1.8 mg in group 2). The postoperative morphine requirements were also reduced during the first 6 h (8.3 +/- 5.8 in group 1 vs. 17.8 +/- 13.4 mg in group 2). The VAS were comparable in both groups, despite the better patients' analgesia score reported in the epidural group during the first 12 h. There was no difference in sedation score at any time interval considered. Epidural and intravenous clonidine reduced heart rate and blood pressure to the same extent. The plasma clonidine concentrations were less in the epidural group only after the loading doses. CONCLUSIONS: Epidural clonidine reduces the intra- and early postoperative analgesic requirements when compared with the same dose given by the intravenous route. The side effects were similar with the two routes of administration. PMID- 8363079 TI - Clonidine and ketanserin both are effective treatment for postanesthetic shivering. AB - BACKGROUND: Although meperidine is an effective treatment of postanesthetic shivering, its mechanism of action remains unknown. Investigation of other drugs might help clarify the mechanisms by which shivering can be controlled. Accordingly, we investigated the efficacy of clonidine, an alpha 2-adrenergic agonist, and ketanserin, a 5-hydroxytryptamine antagonist, in treating postanesthetic shivering. METHODS: First, 54 patients shivering after general anesthesia were allocated randomly to receive an intravenous bolus of saline, 150 micrograms clonidine, or 10 mg ketanserin. A second study explored the dose dependence of clonidine. Forty shivering patients were given saline or clonidine, 37.5, 75, or 150 micrograms. RESULTS: The duration of shivering was significantly shorter in those given clonidine (2.1 +/- 0.9 min) than in the other two groups and shorter in the ketanserin group (4.3 +/- 0.9 min) than in the saline group (12.0 +/- 1.6 min). Clonidine and ketanserin significantly decreased systolic arterial blood pressure when compared to saline. Core rewarming was significantly slower in the clonidine group. In the second study, 37.5 micrograms clonidine was no more effective than saline. Two minutes after treatment, 150 micrograms obliterated shivering in all patients. Five minutes after treatment, all patients given 75 micrograms had stopped shivering. Systolic arterial pressure and heart rate decreased significantly in patients given 75 and 150 micrograms clonidine. CONCLUSIONS: Clonidine (150 micrograms) and ketanserin (10 mg) both are effective treatment for postanesthetic shivering. The effect of clonidine on shivering is dose-dependent: whereas 37.5 micrograms had no effect, 75 micrograms clonidine stopped shivering within 5 min. PMID- 8363080 TI - Autologous platelet-rich plasma does not reduce transfusion of homologous blood products in patients undergoing repeat valvular surgery. AB - BACKGROUND: Patients undergoing cardiac surgery employing cardiopulmonary bypass frequently require transfusion of homologous blood products and, therefore, are exposed to the risk of transfusions. Autologous platelet-rich plasma administration may reduce homologous transfusion and attendant risks. METHODS: In a blinded, randomized fashion, patients undergoing repeat sternotomy and valvular surgery received either a sham product (n = 28) or autologous platelet-rich plasma (n = 28) at the conclusion of cardiopulmonary bypass. Perioperative blood loss, coagulation profiles, and transfusion requirements were compared between the two groups. RESULTS: In the first 24 h postoperatively, both the platelet rich plasma and sham groups received a median of 10.5 units of homologous blood products. Total median perioperative homologous transfusion requirements were 13 and 11.5 units for the platelet-rich plasma and sham groups, respectively. There was no significant difference in intraoperative or postoperative bleeding between the groups. CONCLUSIONS: Autologous platelet-rich plasma did not reduce perioperative bleeding or transfusion requirements in repeat valvular surgery. PMID- 8363081 TI - The medullary dorsal horn. A site of action of morphine in producing facial scratching in monkeys. AB - BACKGROUND: Pruritus is a common side effect of epidural and intrathecal morphine administration in humans. This naloxone-reversible pruritus is typically present on the trunk, but is often severe around the eyes and nose, of the patients. The brain stem has been proposed as the site where opioids act to produce this effect. The authors studied the effect of morphine administered into the medullary dorsal horn (MDH), the brain stem homologue of the spinal dorsal horn, on facial-scratching behavior in monkeys. METHODS: Morphine was unilaterally microinjected into the MDH of rhesus monkeys. Systemic injections of the opioid receptor antagonist naloxone (0.5 mg/kg intramuscularly) were also made in combination with morphine microinjection. Systemic injections of the antihistamine chlorcyclizine (1.0 and 2.5 mg/kg intramuscularly) were also made to determine if facial scratching was mediated through histamine release. The monkeys were videotaped for 10-15 min before and 1-2 h after opioid microinjection, and the number and location of scratches were counted. RESULTS: A dose-response curve was established for the mu/delta-opioid-receptor agonist morphine (0.5, 1.0, 2.5, and 5.0 micrograms). Specificity of the site of action within the MDH was examined by systematically changing the microinjection site, and examining the area of the face that the monkeys scratched. Morphine produced large dose-dependent increases in facial scratching ipsilateral to the microinjection. Increases in facial scratching were also observed contralateral to the microinjections. These effects were reversed by naloxone. The facial area scratched after microinjection of morphine was directly related to the injection site, with 1-mm changes in the location of the microinjection resulting in pronounced changes in the area of the face that the monkeys scratched. Systemic injection of chlorcyclizine produced only a small, transient attenuation of morphine's effect. CONCLUSIONS: Data from this study demonstrate that the MDH is a site where morphine acts to produce facial scratching in monkeys by acting at opioid receptors. It is also likely that the MDH is a site where centrally administered opioids act in producing facial pruritus in humans. The effects of morphine on facial-scratching behavior were only modestly attenuated with chlorcyclizine, indicating a minor involvement of a histamine-dependent mechanism of action. PMID- 8363082 TI - Anesthetics and automaticity in latent pacemaker fibers. IV. Effects of isoflurane and epinephrine or norepinephrine on automaticity of dominant and subsidiary atrial pacemakers in the canine heart. AB - BACKGROUND: Anesthesia and surgery may be associated with atrioventricular junctional or ventricular rhythm disturbances. These may be caused by alteration of automaticity of primary and subsidiary pacemakers. METHODS: The direct effects of isoflurane, alone or in combination with epinephrine (E) and norepinephrine (NE), as well as single effects of E and NE, were examined on automaticity of primary and subsidiary atrial pacemakers (SAP) using a perfused canine right atrial preparation (n = 29). Preparations were perfused with oxygenated Krebs' solution at a constant perfusion pressure of 87 mmHg and a temperature of 36.5 +/ 0.5 degrees C. Delivered concentrations of isoflurane of 1.4 and 2.8% corresponded to measured perfusate concentrations of 315 +/- 7 and 617 +/- 16 microM in experiments with E (n = 14), and 316 +/- 10 and 610 +/- 26 microM in experiments with NE (n = 15). Epinephrine or NE perfusate concentrations were 2 and 5 micrograms/l or 5 and 10 micrograms/l, respectively. To determine the site of earliest activation, extracellular recordings were made from the SA node region and distal sites (approximately 1, 2, and 3 cm) along the sulcus terminalis, the previously reported locations of SAP. Sites of earliest activation shifts from SA node to SAP were scored 1, 2, or 3 depending on the distance from the control pacemaker. The summed shift scores (magnitude score) were normalized by dividing by the total number of preparations for each experimental condition. RESULTS: Exposure to isoflurane, NE, or E alone did not produce a significant increase in the incidence of pacemaker shifts or normalized pacemaker shift scores. Only the high dose of E significantly increased the incidence of pacemaker shifts and normalized shift scores. Dysrhythmogenic potential of E and NE tended to be greater after earlier exposure to isoflurane. Every combination of isoflurane with E or NE produced a significant increase in the incidence of pacemaker shifts and normalized shift scores. CONCLUSIONS: It was concluded that isoflurane with E or NE acts synergistically to increase dysrhythmic potential in the arterial tissue. PMID- 8363083 TI - Comparative efficacy of antiarrhythmic agents in preventing halothane-epinephrine arrhythmias in rats. AB - BACKGROUND: Because the relative efficacy of antiarrhythmic agents on halothane epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na(+)-, K(+)- and Ca(2+)-channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats. METHODS: Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia in 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents. RESULTS: In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11.1 +/- 0.6, and 39.0 +/- 3.9 micrograms/kg, respectively, and the corresponding plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na(+)- and K(+) channel blocker), E-4031 (K(+)-channel blocker), or amiodarone(K(+)-channel blocker with Na(+)-, Ca(2+)-, and beta-blocking activity) increased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 micrograms/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias induced by epinephrine, 16 micrograms/kg intravenously (P < 0.01). CONCLUSIONS: It was concluded that agents with K(+)-channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats. PMID- 8363084 TI - Effects of ketamine on contraction and synthesis of inositol 1,4,5-trisphosphate in smooth muscle of the rabbit mesenteric artery. AB - BACKGROUND: Ketamine acts directly on vascular smooth muscle, causing relaxation. It has been suggested that the mechanism underlying this action involves an interference with transmembrane Ca2+ influx and an inhibition of Ca2+ release from intracellular Ca2+ stores. In vascular smooth muscle cells, agonist-induced Ca2+ release is thought to be mediated by an intracellular second messenger, inositol 1,4,5-trisphosphate (InsP3). To investigate the site at which ketamine acts on agonist-induced contraction, the authors studied the effects of ketamine on contraction and on the synthesis of InsP3 in smooth muscles of the rabbit mesenteric artery. METHODS: Changes in isometric tension of smooth muscle fibers were measured by attaching a thin circular strip from the rabbit mesenteric artery to a strain gauge. To measure the norepinephrine (NE)-induced production of InsP3, smooth muscle strips of the rabbit mesenteric artery were exposed to the agents and homogenized. Inositol 1,4,5-trisphosphate in the supernatant fractions was then assayed. RESULTS: Ketamine dose-dependently inhibited contractions induced by high K+, NE, and histamine in normal Krebs solution. Ketamine also inhibited the NE- or histamine-induced contraction in Ca(2+)-free solution containing 2 mM ethylene-glycol bis-(beta-aminoethylether)-N,N,N',N' tetraacetic acid (EGTA), indicating that this drug inhibits agonist-induced Ca2+ release from intracellular stores. Norepinephrine (10 microM) transiently increased the synthesis of InsP3 in Ca(2+)-free solution, and ketamine (0.1-1.0 mM) inhibited this effect, in a dose-dependent manner. CONCLUSIONS: These results indicate that, in the rabbit mesenteric artery, ketamine inhibits agonist-induced Ca2+ release through its inhibitory action on the agonist-induced synthesis of InsP3. Thus, it is possible that ketamine interferes with the synthesis of intracellular second messengers. PMID- 8363086 TI - Swallowing as a protective reflex for the upper respiratory tract. PMID- 8363085 TI - Hypothermic acid-base management does not affect cerebral metabolic rate for oxygen at 27 degrees C. A study during cardiopulmonary bypass in rabbits. AB - BACKGROUND: It has been contended that, during cardiopulmonary bypass at 27 degrees C, pH-stat management decreases cerebral metabolic rate for oxygen (CMRO2) more than alpha-stat management. In contrast, other studies have not found CMRO2 to differ between techniques. Using each animal as its own control, the authors assessed the effect of alpha-stat versus pH-stat management of CMRO2, cerebral blood flow (CBF), and brain oxygen extraction during cardiopulmonary bypass at 27 degrees C. METHODS: Fourteen New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent cardiopulmonary bypass at 27 degrees C (membrane oxygenator, centrifugal pump, and bifemoral arterial perfusion). Group 1 animals (n = 7) had alpha-stat management for the initial 65-70 min of bypass, and were then changed to pH-stat management for the remaining 30 min of bypass. Group 2 animals (n = 7) had pH-stat management for the initial 65-70 min of bypass, and were then changed to alpha-stat management for the remaining 30 min. Measurement of CBF (radiolabeled microspheres), CMRO2 (CBF x brain arterial venous oxygen content difference), brain temperature, systemic hemodynamics, and arterial blood gases were made in each animal under both alpha-stat and pH-stat conditions. RESULTS: CMRO2 did not differ between alpha-stat and pH-stat conditions (1.4 +/- 0.3 ml.100 g-1.min-1; median +/- quartile deviation), and was independent of order of determination. Changes in CBF between alpha-stat and pH stat conditions were associated with proportional opposite changes in cerebral oxygen extraction. Cerebral blood flow was significantly greater with pH-stat management than with alpha-stat management (37 +/- 5 vs. 30 +/- 3 ml.100 g-1.min 1, respectively). The CBF response to changing PaCO2 was significantly greater when going from alpha-stat to pH-stat conditions (group 1) than in the reverse order (group 2). CONCLUSIONS: During cardiopulmonary bypass at 27 degrees C, hypothermic acid-base management has no measurable effect on CMRO2. CMRO2 was neither extraction limited nor dependent on either PaCO2, CBF, or hemoglobin oxygen affinity differences between alpha-stat and pH-stat management. Cerebral blood flow responses to changing CMRO2 depend on the "starting" conditions, with alpha-stat management appearing to better preserve CBF reactivity than pH-stat management. PMID- 8363087 TI - Transesophageal echocardiographic diagnosis of pulmonary artery catheter entrapment and coiling. PMID- 8363088 TI - Internal common gas line disconnect. PMID- 8363089 TI - Implantable cardiovertor/defibrillator placement in a patient with amiodarone pulmonary toxicity under thoracic epidural anesthesia. PMID- 8363090 TI - Effect of subarachnoid catheter position on the efficacy of intrathecal baclofen for spinal spasticity. PMID- 8363091 TI - Can flumazenil antagonize cardiac responses induced by midazolam. PMID- 8363092 TI - Prior vasectomy and anaphylaxis following protamine: no cause and effect. PMID- 8363093 TI - A normal cervical spine X-ray does not "clear" the patient with suspected cervical spine injury. PMID- 8363094 TI - A simple device to enable capnography during jet ventilation for laryngoscopy. PMID- 8363095 TI - Epidural versus intravenous fentanyl following thoracotomy. PMID- 8363096 TI - An evaluation of proposed graphical symbols for medical devices. PMID- 8363097 TI - Unattended continuous infusion of fentanyl for postoperative pain management. PMID- 8363098 TI - A new device to check the anesthesia machine low-pressure system. PMID- 8363099 TI - Unusual complication of nasotracheal suctioning. PMID- 8363100 TI - The importance of in vitro assay temperature when using volatile anesthetics. PMID- 8363101 TI - Unequivocal determination of sire allele origin for multiallelic microsatellites when only the sire and progeny are genotyped. AB - The effect of a segregating economic trait locus (ETL) can be detected with the aid of a linked genetic marker, if specific alleles of each locus are in association among the individuals genotyped for the genetic marker. For dairy cattle this can be achieved by application of the 'granddaughter design'. If only the sires and their sons are genotyped for the genetic markers, then the allele origin of sons having the same genotypes as their sires cannot be determined. Seven sires and 101 sons were genotyped for five microsatellites. The mean frequency of heterozygous sires was 77%. The mean number of alleles per locus was 8.2. Frequency of informative sons per locus ranged from 60% to 80% with a mean of 72%. With highly polymorphic microsatellites, at least 60% more grandsire families can be included in the analysis, and the number of sons assayed can be reduced by 40%, as compared to diallelic markers. PMID- 8363102 TI - Sequence variation in D-loop mtDNA of cow lineages selected for high and low maternal effects on milk production. AB - The four highest and four lowest cow lineages for milk production were selected from 324 maternal lineages of the Israeli Holstein population. For a single cow from each lineage, the mitochondrial D-loop region was amplified using the polymerase chain reaction and directly sequenced for 719bp. Eighteen polymorphic sites were found of which 17 were substitutions and one was an insertion. Only two alleles were found for each polymorphic site, one of which corresponded to the sequence of Anderson et al. (1982), which was the more frequent allele, in all but two sites. None of the polymorphic sites had an apparent effect on milk production, even though an effect > or = 0.33 phenotypic standard deviations, equivalent to 470 kg milk, could be detected by this experimental design. Furthermore, there was no indication that moderately increasing the sample size would have altered the result, since all rare alleles found in more than a single lineage were found in both the high and low subgroups. PMID- 8363103 TI - DNA sequence analysis of serologically detected ELA class II haplotypes at the equine DQ beta locus. AB - The genetic diversity at the ELA DQ beta locus was investigated using polymerase chain reaction and DNA sequencing. Based upon serological methods 16 class II homozygous animals were selected and their genomic DNA was used. A DQ beta gene from an equine cDNA library was also sequenced. Our methodology and the similarity between the genomic and the cDNA sequences suggest that the studied locus is expressed on equine lymphocytes. In the predicted amino acid sequence the most extensive variation is located at residues 56-60. The pattern of these five amino acids is strongly correlated to the serological ELA class II specificities (W13, W22, W23, Be200). The alleles corresponding to the W23 specificity are the most divergent among the equine DQ beta alleles and also from other mammalian DQ beta sequences. PMID- 8363104 TI - Common swine leucocyte antigen (SLA) haplotypes in NIH and Sinclair miniature swine have similar effects on the expression of an inherited melanoma. AB - Mixed lymphocyte culture and serological typing of NIH and Sinclair miniature swine indicate that the two herds share a common SLA haplotype. NIH haplotype a (International Haplotype H10) appears identical to Sinclair haplotype B, which has significant effects on the penetrance of Sinclair swine cutaneous malignant melanoma (SSCM). Offspring of crosses between melanoma-bearing Sinclair swine homozygous for the B haplotype and non-melanoma NIH aa swine have tumour incidence identical to Sinclair melanoma BB x Sinclair non-melanoma BB offspring. Our results provide further support for the involvement of the swine leucocyte antigen (SLA) complex in the inheritance of SSCM, and identify a new source of non-tumour animals that have all of the genes for SSCM except those at the tumour initiator locus. PMID- 8363105 TI - Haemoglobin I: a new beta-globin chain variant found in sheep of Italian breeds. AB - A rather common haemoglobin variant was detected in the Sardinian and Altamurana sheep breeds. The mutated globin chain appears to be produced under the control of an allele at the HBB locus and due to a neutral amino acid substitution. The variant will be provisionally referred to as the Hb I. PMID- 8363107 TI - A new bovine dinucleotide repeat microsatellite: microsatellite INRA 18. PMID- 8363106 TI - Ovine microsatellites at the OarAE16, OarAE54, OarAE57, OarAE119 and OarAE129 loci. PMID- 8363108 TI - A new bovine dinucleotide repeat microsatellite: microsatellite INRA 30. PMID- 8363109 TI - Ovine microsatellites at the OarHH35, OarHH41, OarHH44, OarHH47 and OarHH64 loci. PMID- 8363110 TI - Ovine microsatellites at the OarVH98, OarVH110, OarVH116, OarVH117 and OarVH130 loci. PMID- 8363111 TI - Ovine microsatellites at the OarVH34, OarVH41, OarVH58, OarVH61 and OarVH72 loci. PMID- 8363112 TI - Effect of standard-dose versus high-dose epinephrine on myocardial high-energy phosphates during ventricular fibrillation and closed-chest CPR. AB - STUDY OBJECTIVE: To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN: Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS: After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS: Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION: High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores. PMID- 8363113 TI - Use of activated charcoal in a simulated poisoning with acetaminophen: a new loading dose for N-acetylcysteine? AB - STUDY OBJECTIVES: To investigate the ability of a supranormal dose of N acetylcysteine to overcome the effects of activated charcoal on N-acetylcysteine bioavailability and to determine the effects of activated charcoal on serum acetaminophen levels. DESIGN, SETTING, AND PARTICIPANTS: Ten healthy adult volunteers participated in a controlled cross-over experiment. During phase I (control), subjects ingested 3 g acetaminophen, followed one hour later by the normal loading dose of N-acetylcysteine (140 mg/kg). During phase II (charcoal), subjects ingested 3 g acetaminophen, followed one hour later by 60 g activated charcoal and a supranormal loading dose of N-acetylcysteine (235 mg/kg). MAIN OUTCOME MEASURES: Serum levels of N-acetylcysteine were measured every 30 minutes for six hours. A serum acetaminophen level was measured at four hours. RESULTS: The area under the curve for N-acetylcysteine was significantly higher for phase II than phase I (P < .05, two-tailed paired t-test). Peak N-acetylcysteine and time to peak were not significantly different. The four-hour serum acetaminophen level was significantly lower for phase II than phase I (P < .05, two-tailed paired t-test). Diarrhea occurred during both phases, but N-acetylcysteine was otherwise well tolerated. CONCLUSION: These results suggest that activated charcoal can be used safely for victims of acetaminophen overdose. A beneficial effect in preventing acetaminophen absorption can be expected if it is given within one hour after ingestion. If N-acetylcysteine is needed because of a toxic serum acetaminophen level, bioavailability can be ensured by increasing the N acetylcysteine loading dose from 140 mg/kg to 235 mg/kg. PMID- 8363114 TI - Cyanide and methemoglobin kinetics in smoke inhalation victims treated with the cyanide antidote kit. AB - STUDY OBJECTIVE: To evaluate serial cyanide, methemoglobin, and carbon monoxide levels in smoke inhalation patients. SETTING: Regional poison center and regional toxicology treatment center. PARTICIPANTS: Seven critically ill smoke inhalation patients referred to the regional poison center. INTERVENTIONS: Peak level and half-life were determined by obtaining serial carboxyhemoglobin, cyanide, and methemoglobin levels. RESULTS: The mean observed half-life of cyanide was 3.0 +/- 0.6 hours. Methemoglobinemia was evaluated in four patients after sodium nitrite administration. The peak measured methemoglobin levels (mean, 10.5% +/- 2%; range, 7.9% to 13.4%) did not occur until a mean of 50 minutes (range, 35 to 70 minutes) following administration of sodium nitrite. The total oxygen-carrying capacity reduced by the combination of carboxyhemoglobin and methemoglobin was never more than 21% (range, 10% to 21%) in this series. CONCLUSION: The administration of sodium nitrite to smoke inhalation patients in the presence of concomitant carbon monoxide poisoning may be relatively safe. PMID- 8363116 TI - Fellowship programs in medical toxicology. PMID- 8363115 TI - Double-blinded comparison of diphenhydramine versus lidocaine as a local anesthetic. AB - STUDY OBJECTIVE: To evaluate the efficacy, onset of action, duration of action, and side effects of 1% diphenhydramine compared with 1% lidocaine when used as a local anesthetic agent. DESIGN: Prospective, double-blinded, cross-over study. SETTING: Emergency medicine residency program, research section. PARTICIPANTS: Ten healthy male volunteers, aged 26 to 38 years old. INTERVENTIONS: Baseline levels of sensation to pinprick (18-gauge needle) within a 2.4-cm-diameter midvolar forearm area and levels of sedation were recorded on 10.2-cm visual analog scales. Subjects then underwent subcutaneous infiltration of 20 mg (2 mL) of the study agent using a 27-gauge needle. Visual analog scale sensation and sedation scores were recorded at five, ten, and 15 minutes and then every 15 minutes until return to baseline. Subjects were studied one week later with the alternate agent. Nonparametric data were analyzed using the Mann-Whitney U test with significance at P < .05. RESULTS: No significant differences in mean pinprick sensation were seen from baseline to 30 minutes. Significant differences were seen at 45 (P = .036) and 60 minutes (P = .036). The mean duration of effective anesthesia was significantly longer for lidocaine than diphenhydramine (81 versus 42 minutes, P = .028). No significant differences were seen in the sedation scores or in the frequencies of local reactions. One subject developed skin necrosis at the injection site with diphenhydramine. CONCLUSION: The duration of local anesthesia for 1% lidocaine was significantly longer and the depth of anesthesia after 30 minutes was significantly higher than that of 1% diphenhydramine. Diphenhydramine resulted in skin necrosis in one test subject. PMID- 8363117 TI - Blood pressure during the first minutes of focal cerebral ischemia. AB - STUDY OBJECTIVE: To determine whether blood pressure declines spontaneously during the first minutes and hours of focal cerebral ischemia. DESIGN: Multiple blood pressure measurements as part of an urgent stroke therapy trial (treatment within 90 minutes of stroke onset). SETTING: Thirteen hospitals in three metropolitan communities. PARTICIPANTS: Sixty-nine patients (mean age, 65 +/- 9 years) with acute ischemic stroke who were participants in a phase I urgent stroke therapy trial of recombinant tissue plasminogen activator. MAIN OUTCOME MEASURE: Blood pressures recorded at the scene of stroke by life-squad personnel, in the emergency department, and in the ICU. RESULTS: The mean time from stroke onset to the time of first blood pressure measurement was 19 +/- 13 minutes. Twenty-four of the 69 patients in the urgent stroke therapy trial had an initial systolic blood pressure of at least 160 mm Hg. Of these, 23 had a significant decline in systolic and diastolic blood pressure during the first 90 minutes after the onset of stroke (mean change in systolic pressure, -29 +/- 22 mm Hg, P < .001; mean change in diastolic pressure, -10 +/- 14 mm Hg, P < .01). No patients received antihypertensive therapy during the time in which the decline in blood pressure was noted. CONCLUSION: Mildly or moderately elevated blood pressure frequently declines spontaneously during the first minutes and hours of focal cerebral ischemia and generally does not require urgent pharmacologic treatment. PMID- 8363118 TI - Safety assessment of high-dose narcotic analgesia for emergency department procedures. AB - STUDY OBJECTIVE: To evaluate the safety of high-dose IV narcotics in patients requiring analgesia for painful emergency department procedures. DESIGN: Prospective multicenter clinical trial. SETTING: Five adult urban EDs. METHODS AND MEASUREMENTS: All patients received IV meperidine (1.5 to 3.0 mg/kg) titrated to analgesia followed by a painful procedure. Vital signs and alertness scale were recorded at regular intervals, and patients were observed for four hours. Adverse events were monitored and documented. Comparisons between baseline and postanalgesia intervals were made with a repeated measures ANOVA (Dunnett's test). RESULTS: Although statistically significant changes in vital signs and alertness scale occurred, they were not clinically significant. Opiate reversal with naloxone was not needed in any patient, and no significant respiratory or circulatory compromise occurred. CONCLUSION: This study of 72 patients demonstrates that high-dose narcotic analgesia is appropriate, well tolerated, and safe when used in selected patients before painful procedures in the ED. Narcotic antagonists and resuscitation equipment nonetheless should be available to maximize safety. PMID- 8363119 TI - Reference accuracy in the emergency medicine literature. AB - STUDY OBJECTIVE: To determine the incidence and nature of errors in the citation and quotation of references contained in the emergency medicine literature. DESIGN: A retrospective analysis of a random sample of articles and references found in the three major emergency medicine journals. SETTING: A university/county hospital. METHODS: We examined single issues of three emergency medicine journals: Annals of Emergency Medicine, Journal of Emergency Medicine, and American Journal of Emergency Medicine. INTERVENTIONS: None. MEASUREMENTS: Four independent reviewers assessed 145 references from 46 referring authors for citational and quotational accuracy. MAIN RESULTS: Major and minor citation errors were found in 10.3% and 17.2% of reference listings, respectively. Qualitative quotational errors were found in 35.2% of references. Eighty-two percent of these errors were considered to be major. Quantitative quotational errors were found in 47% of references reviewed. Secondary rather than primary reference sources were used in 41.4% of references reviewed. CONCLUSION: This study demonstrates a substantial error rate in the citation and quotation of reference sources in the emergency medicine literature. In addition, verification of primary source material was not done by a large percentage of the authors reviewed. Recommendations for improving the accuracy of the emergency medicine literature are offered. PMID- 8363120 TI - Unusual etiology for left flank pain in a 29-year-old man. PMID- 8363121 TI - An introduction to the use of interim data analyses in clinical trials. AB - During a controlled clinical trial, data accumulate that contain information on the relative efficacy of the two treatments, yet these data often are not inspected or analyzed until the planned sample size has been reached and the trial has been terminated. This type of fixed-sample-size trial design, with a single terminal data analysis, has the ethical disadvantage that more patients than are necessary to obtain a reliable result may be randomized to the less efficacious treatment, whichever one that turns out to be. Thus, it often is desirable to schedule one or more analyses of the data, to be conducted before planned termination, to see if a reliable conclusion may be drawn from the data and the trial terminated early. Such analyses are called interim analyses. When interim analyses occur after each of severe relatively large groups of patients, the trial is called a group-sequential trial. Interim data analyses must be planned in advance to avoid increasing the risk of committing a Type I error and to achieve adequate power. This article introduces the statistical issues involved in the planning of interim data analyses and the design of group sequential clinical trials. PMID- 8363122 TI - Accidental administration of activated charcoal into the lung: aspiration by proxy. AB - We report a case of accidental activated charcoal instillation into the lung of a 30-year-old man being managed for a cyclic antidepressant overdose. The patient was treated with multidose activated charcoal, and between his first and second doses, he pulled his nasogastric tube out of position. The tube was reinserted past the endotracheal tube into the right mainstem bronchus, and a dose of activated charcoal with sorbitol was administered into the lung. He subsequently developed an adult respiratory distress syndrome but gradually improved after bronchoscopic removal of charcoal and supportive care. He was discharged 14 days later. PMID- 8363123 TI - Propranolol treatment of albuterol poisoning in two asthmatic patients. AB - The cases of two asthmatic adolescents who overdosed on albuterol are presented. Both patients were tremulous, tachycardic, and hypokalemic. Both were treated successfully with IV propranolol. Neither patient developed bronchospasm. The toxicity of albuterol overdoses and its treatment are discussed. PMID- 8363124 TI - Spontaneous clostridial myonecrosis with abdominal involvement in a nonimmunocompromised patient. AB - Spontaneous clostridial myonecrosis is a rare but aggressive disease usually associated with underlying immunosuppression or malignancy. We present a fatal case of clostridial myonecrosis arising in a patient with intact immune defenses. PMID- 8363125 TI - Fatality secondary to massive overdose of dimenhydrinate. AB - A 19-year-old woman presented with status epilepticus and ventricular dysrhythmias less than one hour after ingesting 5,000 mg dimenhydrinate (Dramamine). Aggressive resuscitation including the use of physostigmine stabilized the cardiac rhythm; however, she suffered a severe neurologic deficit. Development of ischemic and infarcted bowel necessitated colonic resection. After surgery, her condition worsened, and after demonstration of minimal cerebral activity, supportive measures were withdrawn, and she died. Overdose with dimenhydrinate and diphenhydramine, both of which are over-the-counter drugs, can result in rapid central nervous system stimulation, including status epilepticus. Death can occur within two hours. To our knowledge, this is the first reported fatality resulting from ingestion of dimenhydrinate. PMID- 8363126 TI - Phenytoin toxicity from smoking crack cocaine adulterated with phenytoin. AB - Drugs of abuse often are adulterated with agents designed to lower cost or alter the intoxication. Recently, we began to hear of the intentional addition of phenytoin to crack cocaine. We report the cases of five patients with measurable phenytoin levels attributable to smoking crack cocaine adulterated with phenytoin. Three of these patients presented with signs, symptoms, and phenytoin levels consistent with phenytoin toxicity. Clinicians should be aware of this practice when faced with cocaine users with altered mental status, ataxia, or nystagmus. PMID- 8363127 TI - The role of calcium gluconate in the treatment of hydrofluoric acid eye burn. AB - Hydrofluoric acid is used for different purposes in industry and in the home as a rust remover. Most exposures are accidental and may result in severe superficial and deep tissue injury as well as systemic toxicity. There is uncertainty regarding the optimal treatment of hydrofluoric acid eye injury. A patient in whom a solution of 49% hydrofluoric acid induced a large corneal erosion is described. Repeated instillation of 1% calcium gluconate eye drops combined with the conventional treatment of acid eye burns resulted in a complete and quick recovery. PMID- 8363128 TI - On credentials and manpower in emergency medicine. PMID- 8363129 TI - On credentials and manpower in emergency medicine. PMID- 8363130 TI - On credentials and manpower in emergency medicine. PMID- 8363131 TI - On credentials and manpower in emergency medicine. PMID- 8363132 TI - On credentials and manpower in emergency medicine. PMID- 8363133 TI - On credentials and manpower in emergency medicine. PMID- 8363134 TI - On credentials and manpower in emergency medicine. PMID- 8363135 TI - On credentials and manpower in emergency medicine. PMID- 8363136 TI - On credentials and manpower in emergency medicine. PMID- 8363137 TI - On credentials and manpower in emergency medicine. PMID- 8363138 TI - On credentials and manpower in emergency medicine. PMID- 8363139 TI - On credentials and manpower in emergency medicine. PMID- 8363140 TI - On credentials and manpower in emergency medicine. PMID- 8363141 TI - [Therapeutic aspects of hypercholesterolemia in childhood]. PMID- 8363142 TI - [Food preferences among students]. AB - The results of a food preference survey using a questionnaire on 2,567 schoolchildren of sixth, seventh and eighth grade (11 to 14 years of age) from 26 public schools in the city of Barcelona (Spain) are presented. Foods based on potatoes and cereals have the maximum acceptability, followed by dairy and meat products. Chicken is the meat with highest acceptance. Fish has a medium acceptance, and preference for dry beans and peas, fruits and vegetables is lower, although it is high for some specific foods. Important differences among sexes are observed. Boys have higher preference for meat, milk and yogurt, and girls for fish and some vegetables. Differences among genders increase with increasing age. These results are relevant for planning interventions on diet in schools from a health promotion perspective, and for the planning of school lunch programs. PMID- 8363143 TI - [Maternity ward routines in Barcelona]. AB - Twenty-one maternity wards in Barcelona were visited in order to evaluate the degree of compliance with the OMS/UNICEF guidelines for breast-feeding protection. Breast-feeding is initiated within the first hour after birth in only 2 of these hospitals. In only 5 cases is demand feeding encouraged. In only 6 of these maternity wards do the newborn babies remain with their mothers all day long and in only one are newborn babies not given water or dextrose. In only two hospitals is the pacifier discouraged. Furthermore, only two of the hospitals do not receive free formula supplies from the industry. Immediate changes are needed if the mother's right to breast-feed is to be protected. PMID- 8363144 TI - [Severe bone malformations in fetal valproic acid disease]. AB - The dysmorphogenic and teratogenic effects of valproic acid, when administered to pregnant women, have been noted in several reports. We report the case of a 3 month-old infant with multiple congenital anomalies, including severe skeletal malformations, congenital heart defect and facial dysmorphism, whose mother was treated with valproic acid (1000 mg/day) throughout the pregnancy. This is the second published case reporting major skeletal malformations and supports the possible teratogenic effects of valproic acid. PMID- 8363145 TI - [Severe malformations associated with congenital diaphragmatic hernia: conditioning factors for mortality]. AB - We have retrospectively reviewed the clinical records of 42 newborns with congenital diaphragmatic hernia (CDH) treated in our Neonatal Unit between January 1974 and December 1991. In 20 of the children, the CDH was associated with other malformations, which were major in 11 cases (26.2%). The malformations which occurred most frequently were cardiovascular, followed by chromosomal anomalies and those affecting the central nervous system (CNS). All of the newborns with major malformations are included in the high risk group or those with early diagnosis. Overall mortality was 57.1%. Nine out of the 11 cases with major malformations died (81.8%). PMID- 8363146 TI - [Angelman syndrome. Early diagnosis]. AB - We report two patients who were less than two years old that were diagnosed as having Angelman syndrome. Cytogenetic confirmation of the disease was performed. We emphasize clinical and electroencephalographic features in infants that allow an early diagnosis of this syndrome and allow for prompt genetic counseling. PMID- 8363148 TI - [Magnetic resonance++ with gadolinium in Sturge Weber syndrome]. AB - We report four patients with Sturge Weber syndrome in which the pial angioma was visualized better with Gd-DOTA enhanced MR imaging. MR alone demonstrated thickened cortex with diminished convolutions, abnormal white matter and prominent subependymal veins. However, Gd-DOTA enhanced MR imaging improved the visualization of the angioma, localizing and demonstrating the extent of the malformation in Sturge Weber syndrome. We believe that this is the procedure of choice to recognize the extent of the intracranial involvement and which would help to select those patients that would benefit from surgical treatment. PMID- 8363147 TI - [C-peptide in cord blood from macrosomatic and low birth weight for gestational age newborns]. AB - Forty-six newborn babies (11 macrosomic, 11 small-for-dates and 24 of normal weight) have been prospectively studied. The levels of C-peptide in the umbilical blood were determined and the results were statistically analyzed for relationships to several perinatal variables of the mother, newborn and placenta. A positive correlation between C-peptide levels and neonatal weight, newborn ponderal index and maternal weight-gain during gestation were observed. Some other variables strongly related to neonatal infant weight (maternal weight, net placental weight and placental volume) were independent of C-peptide levels. PMID- 8363149 TI - [Homocystinuria: effectiveness of the treatment with pyridoxine, folic acid, and betaine]. AB - We present the results achieved with vitamin (pyridoxine and folic acid) and betaine (trimethyl-glycine) treatment of three patients with homocystinuria. Cases 1 and 2 were detected by having clinical findings suggestive of the disease (ocular and orthopedic alterations) and case 3 was diagnosed after a family metabolic screening was done. All presented a positive Brand's test and an abnormal elevation of plasma and urine homocysteine, as well as high methionine and low cystine levels in the plasma. Initially, when pyridoxine (600 mg/d) and folic acid (10 mg/d) were given for one month, a partial fall in the homocysteine levels was observed in cases 2 and 3, but not in case 1. When betaine was added (6 g/d), homocysteine disappeared from the plasma after the first month in cases 2 and 3, but only after the third month in case 1. Case 1 also showed a moderate clinical improvement in behavior and school performance. The treatment was maintained for two years in case 1, and for one year in cases 2 and 3. After betaine therapy, no disturbances were observed in the hepatic, renal and bone marrow functions, nor were there any clinically relevant ill-effects. These findings show that betaine offers a therapeutic alternative in the treatment of this disease, independent of the patient's response to pyridoxine. PMID- 8363150 TI - [Neonatal conjunctivitis: microbiologic study and antibiotic sensitivity]. AB - We have analyzed retrospectively fifty conjunctival samples from infants less than one month of age affected with conjunctivitis. Of these samples, 84% had a positive bacterial culture, with the microorganisms isolated, in order of frequency, being: Staphylococcus epidermidis (14%), Staphylococcus aureus (14%), Streptococcus pneumoniae (12%), Haemophilus sp, Chlamydia and alpha-hemolytic Streptococcus (8%). All of these showed a high sensitivity to most of the drugs tested, except to penicillin and its derivatives. Cefotaxime, ceftriaxone and ciprofloxacin showed the highest in vitro activities. Of the pharmacological ophthalmic preparations commercially available in our country, sulfonamides, chloramphenicol, rifampicin, erythromycin and tobramycin are the agents more active against the bacteria described above. PMID- 8363151 TI - [Organochlorine compounds: blood levels in mothers, newborns, and infants, in maternal milk and formula. Study in the province of Huelva]. AB - We have studied the presence of organochlorine compounds (OCC), DDT, HCB, HCH and isomers alpha, beta and gamma or lindane, hepta-chloro-epoxide (HE) and polychlorobiphenyl compounds (PCB), in 50 mothers and their newborn babies. The samples studied included the umbilical cord blood, blood from the mothers during the delivery, blood from the baby at one and three months of age, and the milk fed to the babies at these periods (breast n = 30; bottle n = 20). The objectives of the study were: 1) To detect the levels of OCC in the different samples. 2) To discover the difference in levels between breast and bottle fed babies. 3) To quantify the variations of the levels in the different samples. 4) To check whether the acceptable daily intake (ADI) established for these OCC is exceeded among these babies. The analyses were done in the National Institute of Toxicology in Seville, by using the following methods, gas chromatography, electron capture detector and mass spectrometry. The statistical analysis was based on the Kruskal-Wallis, Shapiro-Wilks, Levene, Pooled and Separate tests. We have found significant levels of OCC in the samples analyzed. The PCBs are the compounds in our study which have the highest levels, indeed being one of the highest levels documented to date. We verify the decline in OCC of agricultural origin in relation to previous reports in our country, as has also been reflected in the international literature in recent years. The levels of OCC in breast fed babies are significantly higher than those in bottle fed babies. PMID- 8363152 TI - [Study of Navarra (PECNA). Correlation of arterial blood pressure, in a child young population, with anthropometric and biochemical parameters]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescent in Navarra, arterial blood pressure (BP) readings were taken in 5,829 children. These children, both males and females, between the ages of 4 and 17 years, were selected at random from the public and private school population in our community. The correlation between systolic blood pressure and diastolic blood pressure with anthropometric and biochemical parameters was analyzed. The correlation coefficient for systolic BP readings were always higher than those for diastolic BP. The highest correlations for both BP scores were found with weight, followed by height. Correlation with total weight parameters is superior to that found with body fat parameters. There were no significant correlations between BP and the lipid parameters. When analyzing multiple regression equations, we find that with only the child's weight and age, both systolic and diastolic BP can be predicted with correlation coefficients of 0.597 and 0.492, respectively. When doing a partial correlation analysis, the correlation between systolic BP and age, at a fixed height value, disappears; while the correlation of systolic BP with height remains when using a set age. This suggest that the best definition for hypertension is based on BP-height percentile, rather than BP age. PMID- 8363153 TI - [Coffin-Siris syndrome. Review of the literature]. PMID- 8363154 TI - [Incidence of Candida infections in very low birth weight newborns. Importance of an early diagnosis and evaluation of therapeutic approaches]. PMID- 8363155 TI - [Omphalocele and gastroschisis. Report of 14 cases]. PMID- 8363156 TI - [Seckel syndrome: study of 2 new cases]. PMID- 8363157 TI - [Bullous mastocytosis (diffuse cutaneous mastocytosis): report of a case and review of the literature]. PMID- 8363158 TI - [Treatment with imipenem-cilastatin in a girl with resistant pneumococcal meningitis]. PMID- 8363160 TI - [Congenital postero-medial angulation of the tibia]. PMID- 8363159 TI - [Ileal ulcer as a cause of rectal hemorrhage]. PMID- 8363161 TI - [Congenital adrenal gland hypoplasia with sudden death in an 18-month-old child. Necropsy study]. PMID- 8363162 TI - [Mediastinal tubercular abscess]. PMID- 8363163 TI - [Acute airway obstruction in an infant, secondary to laterocervical abscess]. PMID- 8363164 TI - Efficacy of psyllium in reducing serum cholesterol levels in hypercholesterolemic patients on high- or low-fat diets. AB - OBJECTIVES: To determine the efficacy of psyllium in reducing serum cholesterol levels in patients on high- or low-fat diets. DESIGN: Double-blind, placebo controlled, 16-week parallel trial. The study included an 8-week baseline period and an 8-week treatment period. PATIENTS: Healthy men and women, 21 to 70 years old, with primary hypercholesterolemia (total serum cholesterol > or = 5.7 mmol/L [220 mg/dL]). Thirty-seven participants followed a high-fat diet and 81 participants followed a low-fat diet. INTERVENTION: Participants were randomly assigned to either psyllium, 5.1 g twice a day, or placebo. MEASUREMENTS: Fasting lipid and apolipoprotein concentrations, including direct low-density lipoprotein (LDL) cholesterol quantification; nutritional analyses of 4 days of 7-day food records to monitor dietary compliance; and physical examinations, clinical chemistry and hematologic studies, and urinalysis to assess treatment safety. MAIN RESULTS: Psyllium recipients in both the high- and low-fat diet groups showed small but significant decreases (P < 0.05) in total cholesterol and low density lipoprotein (LDL) cholesterol levels. Total cholesterol and LDL cholesterol levels decreased 5.8% and 7.2%, respectively, in psyllium recipients on high-fat diets and 4.2% and 6.4%, respectively, in psyllium recipients on low fat diets. No significant difference was seen in LDL cholesterol response when psyllium recipients on low- and high-fat diets were compared (P > 0.2). No significant reductions in lipid levels were observed in placebo recipients. Based on the National Cholesterol Education Program LDL cholesterol classification system, 39% of the psyllium recipients improved in LDL cholesterol classification (P < 0.0001) compared with 20.3% of placebo recipients (P > 0.2). CONCLUSIONS: Psyllium produces a modest but significant improvement in total cholesterol and LDL cholesterol levels in persons on either low-fat or high-fat diets. Psyllium, when added to a prescribed low-fat diet, may obviate the need for typical lipid lowering medications or may prove to be a valuable adjunct to other treatments in patients with moderately elevated LDL cholesterol levels. PMID- 8363165 TI - A linoleate-enriched cheese product reduces low-density lipoprotein in moderately hypercholesterolemic adults. AB - OBJECTIVE: To test the effect of substituting a modified-fat cheese product into the diets of hypercholesterolemic adults. DESIGN: A 4-month, randomized, double blind, crossover substitution trial. SETTING: General community outpatient study. PARTICIPANTS: Twenty-six healthy adult volunteers (17 men, 9 women) with moderate hypercholesterolemia (total cholesterol > 5.69 mmol/L but < 7.24 mmol/L). INTERVENTION: Daily substitution of 100 g of cheese, either partial skim-milk mozzarella or modified-fat (vegetable oil) mozzarella cheese product, into participants' normal diets. Participants consumed an assigned cheese for 2 months, at which time they crossed over to consume the other study cheese. MAIN OUTCOME MEASURES: Plasma lipid and apolipoprotein levels were measured at baseline and at 2 and 4 months after initiation of the study. Compliance was assessed by body weight and by biweekly dietary records and interviews. RESULTS: No differences in weight or in the amount or type of calories consumed were found during the study. No statistically significant changes in lipid values resulted from consumption of mozzarella cheese. Modified-fat cheese substitution resulted in a decreased low-density lipoprotein cholesterol level when compared with levels at both baseline (-0.28 mmol/L; 95% Cl, -0.14 to -0.42 mmol/L) and during consumption of the skim-milk mozzarella cheese (-0.38 mmol/L; 95% Cl, -0.2 to 0.70 mmol/L). Findings for total cholesterol were similar. High-density lipoprotein cholesterol, plasma triglyceride, and apolipoprotein A-l and B-100 levels were unaltered. Both sexes responded similarly. CONCLUSIONS: A linoleate enriched cheese product, in the absence of any other changes in diet or habits, substituted into the normal diets of hypercholesterolemic adults reduced low density lipoprotein and plasma cholesterol levels. PMID- 8363166 TI - Prosthetic valve endocarditis resulting from nosocomial bacteremia. A prospective, multicenter study. AB - OBJECTIVE: To determine the incidence of endocarditis in bacteremic patients with prosthetic heart valves and the risk factors for and the effect of duration of antibiotic therapy on development of endocarditis in such patients. DESIGN: Multicenter, prospective observational study. SETTING: Six university teaching hospitals with high-volume cardiothoracic surgery. PARTICIPANTS: One hundred seventy-one consecutive patients with prosthetic heart valves who developed bacteremia during hospitalization. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated when they were identified as having bacteremia and 1, 2, 6, and 12 months after its occurrence. Of 171 patients, 74 (43%) developed endocarditis: Fifty-six (33%) had prosthetic valve endocarditis at the time bacteremia was discovered ("endocarditis at outset"), whereas 18 (11%) developed endocarditis a mean of 45 days after bacteremia was discovered ("new endocarditis"). Mitral valve location and staphylococcal bacteremia (Staphylococcus aureus or S. epidermidis) were significantly associated with the development of "new" endocarditis. All 18 cases of new endocarditis were nosocomial, and in 6 of these cases (33%) bacteremia was acquired via intravascular devices. Twenty-one patients without evidence of endocarditis at the time of bacteremia received short-term antibiotic therapy (< 14 days); 1 patient (5%) developed endocarditis. Eleven of 70 patients (16%) who received long-term antibiotic therapy (> 14 days) developed endocarditis (P > 0.2). CONCLUSIONS: Bacteremic patients with prosthetic heart valves were at notable risk for developing endocarditis, even when they received antibiotic therapy before endocarditis developed and regardless of the duration of such therapy. Intravascular devices were a common portal of entry. PMID- 8363167 TI - Pituitary-testicular function in nephropathic cystinosis. AB - OBJECTIVE: To evaluate reproductive function in patients with cystinosis and in renal transplant recipients without cystinosis. DESIGN: Cross-sectional study. SETTING: Clinical Center, National Institutes of Health. PATIENTS: Ten male patients, 15 to 28 years old, with nephropathic cystinosis and renal allografts formed the study group; 11 renal transplant recipients who had a primary renal disorder other than cystinosis and were matched with study patients for age and renal function served as the control group. MEASUREMENTS: Tanner staging, serum gonadotropin determinations, and testosterone and testosterone-binding globulin assessments. Selected patients also had a human chorionic gonadotropin (HCG) stimulation test, a gonadotropin-releasing hormone (GnRH) stimulation test, and serial sampling for luteinizing hormone (LH). MAIN RESULTS: Although testosterone levels were within normal limits in 7 of 10 patients with cystinosis, the mean testosterone level in patients with cystinosis was 11.5 +/- 2.0 nmol/L compared with 24.2 +/- 3.0 nmol/L in control patients (P < 0.005). No patient with cystinosis reached Tanner stage 5 (full pubertal development), whereas 9 of 11 control patients did. Seven of 10 patients with cystinosis had elevations in LH or follicle-stimulating hormone (FSH) levels, suggesting testicular failure. These patients also had normal LH and FSH responses after GnRH stimulation, increased LH pulse frequency, and reduced testosterone response after HCG stimulation. In comparison, only 3 of 11 control patients had minimally elevated gonadotropin levels, and all 11 had normal testosterone levels. Microscopic testicular examination in one patient showed cystine crystals, germinal dysplasia, increased fibrosis, and Leydig cell hyperplasia. CONCLUSIONS: Abnormalities in the pituitary-testicular axis are common in male patients with cystinosis. These changes appear to be related to the disease cystinosis and not to treated renal failure per se. PMID- 8363168 TI - Acute liver disease associated with erythromycins, sulfonamides, and tetracyclines. AB - OBJECTIVE: To determine whether erythromycins, sulfonamides, and tetracyclines are associated with an increased risk for acute hepatitis. DESIGN: Case-control study. SETTING: Medicaid billing data from Michigan and Florida between 1980 and 1987. PATIENTS: The 107 cases included patients hospitalized with acute symptomatic hepatitis without an identifiable cause of liver disease noted in the medical record. Four controls per case were randomly selected and were matched for age, sex, and state. RESULTS: Five cases (4.7%) and four controls (0.9%) were exposed to erythromycins, yielding an odds ratio of 5.2 (95% Cl, 1.1 to 26.6). No case or control was exposed to erythromycin estolate. Eight cases (7.5%) and three controls (0.7%) were exposed to oral sulfonamides, yielding an odds ratio of 11.4 (Cl, 2.7 to 67.8). All (except one control) had received trimethoprimsulfamethoxazole. Five cases (4.7%) and four controls (0.9%) were exposed to tetracyclines, yielding an odds ratio of 5.2 (Cl, 1.4 to 19.7). The results did not change substantively for erythromycin or sulfonamides after adjustment using multiple logistic regression for age, sex, state, and use of other hepatotoxic drugs. With tetracyclines, however, the odds ratio decreased to 3.6 (Cl, 0.9 to 14.3). Associations were also seen with isoniazid (P = 0.008) and rifampicin (P = 0.04). The number of patients developing acute symptomatic liver disease resulting in hospitalization for each million patients treated with a 10 day course of erythromycin was 2.28 cases; for sulfonamides, this figure was 4.8 cases; and for tetracycline, the figure was 1.56 cases. CONCLUSION: Erythromycin, sulfonamides, and tetracyclines are associated with acute symptomatic hepatitis resulting in hospitalization. Given the widespread use of these drugs, they will be among the more common drugs associated with hepatitis. PMID- 8363170 TI - Primary cutaneous tuberculosis after a needlestick injury from a patient with AIDS and undiagnosed tuberculosis. PMID- 8363169 TI - Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. AB - OBJECTIVE: To compare the efficacy and toxicity of single daily dosing of amikacin and ceftriaxone with that of multiple daily dosing of amikacin and ceftazidime for febrile episodes in patients with cancer and granulocytopenia. DESIGN: A prospective, randomized, unblinded, multicenter trial. SETTING: Twenty one tertiary care or university medical centers. PATIENTS: Six hundred seventy seven patients with cancer and granulocytopenia (858 febrile episodes). INTERVENTIONS: Random assignment to empiric therapy with a single daily dose of amikacin (20 mg/kg) and ceftriaxone (adults, 30 mg/kg; children, 80 mg/kg) (24 hour group) or with multiple daily doses of amikacin (6.5 mg/kg every 8 hours) and ceftazidime (33 mg/kg every 8 hours) (8-hour group). MEASUREMENTS: Percentage response to each regimen and occurrence of nephrotoxicity and ototoxicity. RESULTS: Single daily dosing of amikacin and ceftriaxone was as effective as multiple daily dosing of amikacin and ceftazidime (71% compared with 74%; difference, -3%; 95% Cl, -10% to 3%; P > 0.2). Equivalent responses also were noted for each category of infection. Median peak (30 minutes after a 60-minute infusion) serum concentrations of amikacin were higher in the 24-hour group than in the 8-hour group (45.6 compared with 21 micrograms/mL, P < 0.001), whereas trough (preinfusion) levels were lower (0.9 compared with 2 micrograms/mL, P < 0.001). Nephrotoxicity was 3% in the 24-hour group and 2% in the 8-hour group (difference, 1%; Cl, -1% to 4%). Increases in serum creatinine, however, were delayed (P = 0.048) and smaller (P = 0.06) in the 24-hour group than in the 8 hour group and occurred almost exclusively after other nephrotoxic drugs were added. Audiometry was only done in 144 patients (21%). Ototoxicity was 9% in the 24-hour group and 7% in the 8-hour group (difference, 2%; Cl, -7% to 11%; P > 0.2). Further infections developed in 15% and 12% of patients, respectively (difference, 3%; Cl, -2% to 9%). The overall mortality rate was 11% in both treatment groups (difference, 0%; Cl, -5% to 5%). CONCLUSIONS: Single daily dosing of amikacin and ceftriaxone was as effective and no more toxic than multiple daily dosing of amikacin and ceftazidime for the empiric therapy of infection in patients with cancer and granulocytopenia. PMID- 8363171 TI - Effect of garlic on total serum cholesterol. A meta-analysis. AB - OBJECTIVE: To assess the size and consistency of garlic's effect on total serum cholesterol in persons with cholesterol levels greater than 5.17 mmol/L (200 mg/dL). DATA SOURCES: Clinical trials were identified by a computerized literature search of MEDLINE and by an assessment of the bibliographies of published studies and reviews. STUDY SELECTION: Trials were selected if they were randomized and placebo-controlled and if at least 75% of their patients had cholesterol levels greater than 5.17 mmol/L (200 mg/dL). Studies were excluded if they did not provide enough data to compute effect size. Five of 28 studies were selected for review. DATA EXTRACTION: Details of study design, patient characteristics, interventions, duration of therapy, and cholesterol measurements were extracted by one author and were verified by another. DATA SYNTHESIS: Study quality was evaluated by multiple reviewers using a closed-ended questionnaire. Patients treated with garlic consistently showed a greater decrease in total cholesterol levels compared with those receiving placebo. Meta-analysis of homogeneous trials estimated a net cholesterol decrease attributable to garlic of 0.59 mmol/L (95% CI, 0.44 to 0.74) (23 mg/dL [CI, 17 to 29]) (P < 0.001). CONCLUSIONS: Meta-analysis of the controlled trials of garlic to reduce hypercholesterolemia showed a significant reduction in total cholesterol levels. The best available evidence suggests that garlic, in an amount approximating one half to one clove per day, decreased total serum cholesterol levels by about 9% in the groups of patients studied. PMID- 8363172 TI - Treatment of gallstones. AB - PURPOSE: To critically review the risks and benefits of therapy for asymptomatic and symptomatic persons with gallstones who are considering therapy to prevent future episodes of biliary pain or complications including acute cholecystitis, pancreatitis, or gallbladder cancer. DATA SOURCES: Review of English-language literature regarding the natural history of persons with gallstones and the operative mortality rates for open cholecystectomy and laparoscopic cholecystectomy. Mathematical simulation modeling was used to derive estimates of lifetime risks for gallstone-related mortality and for life expectancy, for prophylactic cholecystectomy and expectant management, for men and women of different ages. RESULTS: For persons with asymptomatic gallstones, natural history is so benign that treatment is generally not recommended. For persons with symptomatic gallstones, (that is, that have caused an episode of biliary pain), the rate for subsequent pain is high so that many persons probably choose cholecystectomy to avoid pain; however, about 30% of persons who have had pain do not have further episodes of pain. The expected loss of life for persons with symptomatic stones managed expectantly is roughly several months, on average, and may not be considered high enough in itself to warrant therapy. Although laparoscopic cholecystectomy has become popular with patients and physicians, its safety is yet unknown compared with open cholecystectomy. CONCLUSION: Prophylactic cholecystectomy should be recommended for most persons with symptomatic gallstones unless the person wants to try a period of watchful waiting to see if pain recurs. Nonsurgical therapy may be suitable for persons with high operative risk. For persons with asymptomatic gallstones, watchful waiting is the best course. PMID- 8363173 TI - A conflict of interest. PMID- 8363174 TI - The quest for a cholesterol-decreasing diet: should we subtract, substitute, or supplement? PMID- 8363175 TI - Here come the couples. PMID- 8363176 TI - Weight loss and mortality. PMID- 8363177 TI - Acute mountain sickness at moderate altitudes. PMID- 8363178 TI - Acute mountain sickness at moderate altitudes. PMID- 8363179 TI - Management of thyroid nodules. PMID- 8363180 TI - Treatment of gastrointestinal motility disorders in pregnancy. PMID- 8363181 TI - Effect of HIV infection on response to syphilis. PMID- 8363182 TI - Polymorphism of IgG Fc receptors in meningococcal disease. PMID- 8363183 TI - Alopecia associated with fluconazole treatment. PMID- 8363184 TI - Failure of APSAC thrombolysis. PMID- 8363185 TI - The blurred intersection of beneficence, competence, and autonomy. PMID- 8363186 TI - More on the common communion cup. PMID- 8363187 TI - More on the common communion cup. PMID- 8363188 TI - Methods for Voluntary Weight Loss and Control. Proceedings of NIH Technology Assessment Conference. Bethesda, Maryland, 30 March-1 April 1992. PMID- 8363189 TI - Cultural and psychosocial determinants of weight concerns. AB - Several sociocultural and psychological factors underlie Western society's intense preoccupation with the body. These factors include the social value of attractiveness, the strong correlation between attractiveness and perceived fitness, the interrelation among attractiveness, a good body image, and feelings of self-worth, and the relation between pressures to succeed in both the appearance- and work-related domains. The strong societal emphasis on appearance and slimness has translated to both intense body preoccupation and a willingness to try almost any weight-loss strategy. Thus, dieting occurs across all weight categories in response to these powerful social and psychological motivators. PMID- 8363190 TI - Descriptive epidemiology of body weight and weight change in U.S. adults. AB - Data on body weight and weight change collected from nationally representative samples of U.S. adults are reviewed. The body mass index (weight [kg]/height [m2]) has a low correlation with height and is used to compare body weights between persons of differing heights. The BMI varies to a greater degree in women than in men. Below the 75th percentile of the BMI distribution, women have lower BMIs than men, whereas at the 75th percentile and above, women have higher BMIs than men. Overweight is defined as a BMI of 27.8 or more in men and of 27.3 or more in women, corresponding to approximately 20% or more above desirable weight in the 1983 Metropolitan Life Insurance Company tables. For persons of average height (men, 5'9"; women, 5'4") this definition is equivalent to a body weight above 85 kg (187 pounds) in men and above 72 kg (158 pounds) in women. Among adults 20 to 74 years of age, 24% of men and 27% of women are overweight, yielding an estimated total of 34 million persons in the United States. The prevalence of overweight increases with age, for both men and women but to a greater degree in women. Blacks and Hispanics have a higher prevalence of overweight than do whites, especially among women. Between 1960 and 1980, the prevalence of overweight among whites increased by 3% in women and by 6% in men. In blacks, however, the prevalence of overweight increased by 7% in women and by 28% in men. Longitudinal body weight measurements taken 10 years apart show that adults younger than 55 years tend to gain weight, whereas those 55 years and older tend to lose weight. The youngest adults gain the most weight, and the oldest adults lose the most weight. In all age groups, women have substantially greater variation in their 10-year weight change than do men. PMID- 8363191 TI - Special issues regarding obesity in minority populations. AB - Special attention must be given to obesity as it occurs in and affects ethnic minorities (that is, black Americans, Hispanic Americans, Asian and Pacific Islander Americans, American Indians and Alaska Natives, and Native Hawaiians) in the United States. In most of these groups, the prevalence of obesity is substantially higher than in whites, especially among women. Poverty and lower educational attainment, which are associated with higher than average rates of female obesity (independent of ethnicity), affect proportionately more persons in these minority populations than in white populations. Diabetes mellitus and certain other obesity-related conditions occur to a markedly greater than average extent in many minority populations. A high-risk body fat distribution (upper body or central obesity) occurs to a greater extent in some minority populations than in whites. Because of situational and cultural factors, effective obesity prevention and treatment approaches may need to be defined on an ethnicity specific basis. Increased attention to obesity as it occurs in and affects diverse ethnic groups can help to address critical minority health issues. Such efforts can also broaden and enrich aspects of obesity research for which models based on white populations are inappropriate or limited. PMID- 8363192 TI - Medical hazards of obesity. AB - The medical hazards of obesity are discussed. Risks include insulin resistance, diabetes mellitus, hypertriglyceridemia, decreased levels of high-density lipoprotein cholesterol, and increased levels of low-density lipoprotein cholesterol. Obesity is also associated with gallbladder disease and some forms of cancer as well as sleep apnea, chronic hypoxia and hypercapnia, and degenerative joint disease. Obesity is an independent risk factor for death from coronary heart disease. A central distribution of body fat enhances the risk for most of these conditions. PMID- 8363193 TI - Weight control practices of U.S. adults trying to lose weight. AB - OBJECTIVE: To estimate the relative prevalence of different types and combinations of practices among weight-loss practitioners and to describe the relations between individual characteristics and various features of weight-loss regimens. DESIGN: A telephone survey of a random digit-dialed probability sample of adults in the continental United States who reported that they were trying to lose weight. PARTICIPANTS: A total of 1431 persons 18 years or older who were attempting to lose weight. MEASUREMENTS: Self-reports of a detailed inventory of more than 35 specific practices that might be used as part of a voluntary weight loss plan, along with information about individual characteristics such as current weight, weight-loss history, demographic profile, motivations to lose weight, sources of information, and knowledge about diet and health. RESULTS: The average respondent had a current weight-loss attempt lasting from 5 to 6 months, had tried a similar plan before, and had averaged one attempt a year for the past 2 years. Seventy-one percent of women and 62% of men reported that they were both changing their diet and exercising more as part of a current weight-loss attempt. Frequently reported weight-loss practices included weighing oneself regularly (71% and 70% for women and men, respectively), walking (58% and 44%), using diet soft drinks (52% and 45%), taking vitamins and minerals (33% and 26%), counting calories (25% and 17%), skipping meals (21% and 20%), using commercial meal replacements, (15% and 13%), taking diet pills (14% and 7%), and participating in organized weight-loss programs (13% and 5%). Sex, education, and overweight status influenced the choice of a weight-loss practice. CONCLUSIONS: Individual approaches to weight-loss vary and are characterized by their duration and by their recurrent nature. Policy efforts should be directed toward increasing the long-term effectiveness of individual weight-loss plans. PMID- 8363194 TI - Weight control practices of U.S. adolescents and adults. AB - OBJECTIVE: To estimate the prevalence of various weight-loss practices in U.S. adolescents and adults. DESIGN: The Youth Risk Behavior Survey, a self administered survey of a random sample of high school students in 1990 and the Behavioral Risk Factor Surveillance System, a random-digit dial survey in 1989. SETTING: Thirty-eight states and the District of Columbia. PARTICIPANTS: High school students (n = 11,467) and adults 18 years and older (n = 60,861). RESULTS: Among high school students, 44% of female students and 15% of male students reported that they were trying to lose weight. An additional 26% of female students and 15% of male students reported that they were trying to keep from gaining more weight. Students reported that they had used the following weight control methods in the 7 days preceding the survey: exercise (51% of female students and 30% of male students); skipping meals (49% and 18%, respectively); taking diet pills (4% and 2%, respectively); and vomiting (3% and 1%, respectively). Among adults, 38% of women and 24% of men reported that they were trying to lose weight, whereas 28% of each sex reported that they were trying to maintain their weight. CONCLUSIONS: Attempts to lose or maintain weight are very prevalent among both adolescents and adults, especially among females. PMID- 8363195 TI - Who in America is trying to lose weight? AB - OBJECTIVES: To describe the characteristics and weight-loss methods of persons who are trying to lose weight; to compare the knowledges and practices regarding weight loss between those persons trying to lose weight and those not trying to lose weight; and to evaluate trends in these knowledges and practices between 1985 and 1990. DESIGN: Large (approximately 120,000 persons per year), nationally representative random sample of the U.S. population. SETTING: The 1985 and 1990 Health Promotion Disease Prevention Current Health Topics Supplements to the National Health Interview Survey. PARTICIPANTS: Random sample of the U.S. population. MEASUREMENTS: Proportions of the NHIS sample with characteristics of interest weighted to be representative of the U.S. population. RESULTS: Approximately 44 million persons 25 years or older were trying to lose weight in 1990; 61.8% of men and 59.6% of women were doing so by increasing their physical activity. Both proportions are significantly increased compared to the 1985 proportions of 56.9% and 56.2%, respectively. Twenty-seven percent of those persons who saw themselves as overweight were not trying to lose weight. CONCLUSIONS: More than one third of Americans see themselves as overweight, but fewer than two thirds of these persons are trying to lose weight. About 4% of self-perceived underweight persons and 11.4% of persons who think their weight was about right are also trying to lose weight. Most persons who are trying to lose weight are doing so by eating less, by increasing their physical activity, or by a combination of these methods. PMID- 8363196 TI - Proposed standards for judging the success of the treatment of obesity. AB - The purpose of this report is to propose standards for the successful treatment of obesity. This process is somewhat arbitrary because obesity is a multifactorial disease and because standards need revision as diagnostic and treatment techniques improve. Weight loss, the classic standard of success, does not account for individual variability. Reduction in other measures of body size, such as body mass index, percentage of excess weight, and body fat, may be preferable. Improvement in known complications of obesity (diabetes mellitus, hypertension, hyperlipoproteinemia, sleep apnea, and psychosocial problems) are equally valid measures of success. Because obesity is a chronic disease, maintenance of weight loss is included as a standard of success. Response to obesity treatment varies, and thus criteria to define minimal, intermediate, and full success for each variable are necessary. PMID- 8363197 TI - Evidence for success of caloric restriction in weight loss and control. Summary of data from industry. AB - Data voluntarily supplied by industry were examined to evaluate the success of commercial weight loss programs and products. Information about the safe loss of weight, the maintenance of this lowered weight, and resultant health benefits were reviewed. Information was received from companies that produce over-the counter preparations designed for persons with a small weight loss goal and from physician-supervised programs for morbidity obese persons placed on very-low calorie diets. Regardless of the products used, successful weight loss and control was limited and required individualized programs consisting of restricted caloric intake, behavior modification, and exercise. Although some manufacturers of physician-supervised weight loss products for obese persons hav defined the effectiveness of their programs with controlled clinical studies, other industry programs have only begun to accurately assess their effectiveness or safety. Given the importance to public health of reducing obesity, rigorous studies on current weight control practices should be pursued aggressively. PMID- 8363198 TI - Treatment of obesity by moderate and severe caloric restriction. Results of clinical research trials. AB - Recent studies of the treatment of obesity by moderate and severe caloric restriction show that patients treated in randomized trials using a conventional 1200 kcal/d reducing diet, combined with behavior modification, lose approximately 8.5 kg in 20 weeks. They maintain approximately two thirds of this weight loss 1 year later. Patients treated under medical supervision using a very low-calorie diet (400 to 800 kcal/d) lose approximately 20 kg in 12 to 16 weeks and maintain one half to two thirds of this loss in the following year. Both dietary interventions are associated with increasing weight regain over time, although regain can be minimized with the recognition that obesity, in many cases, is a chronic condition that requires continuing care. Patients who participate in a formal weight-loss maintenance program, exercise regularly, or both are likely to achieve the best long-term results. PMID- 8363199 TI - Obesity treatment: can diet composition play a role? AB - Diet composition can play a role in obesity treatment because it can influence energy intake and nutrient balance. The greatest potential effect of diet composition occurs not during weight reduction but during maintenance of a reduced body weight. During weight reduction, the extent of negative energy balance is the greatest determinant of the amount and rate of weight loss, and any effects of diet composition are likely to be very small. Conversely, during the maintenance period after weight reduction, maintenance energy requirements are reduced and the rate of fat oxidation may be low. Prevention of fat storage and regain of body weight can be achieved either by increasing fat oxidation (for example, by increasing exercise) or by reducing the fat content of the habitual diet. The treatment with the greatest chance for success combines a reduced-fat diet with aerobic exercise. PMID- 8363200 TI - Evidence for success of behavior modification in weight loss and control. AB - Behavior modification applied to the treatment of obesity has evolved from the environmental control of eating behavior to a broader approach characterized by systematic manipulation of all factors associated with eating and exercise patterns. This approach has shown success in helping obese persons lose modest amounts of weight. The average length of treatment is 18 weeks, and the average weight loss is 9.9 kg. About 66% of these weight losses are maintained at 52 weeks of follow-up. Because obesity is a chronic condition with a substantial potential for relapse, longer-term treatments are needed. In the future, behavioral modification is likely to be further combined with other treatment methods. PMID- 8363201 TI - Evidence for success of exercise in weight loss and control. AB - Physically active men and women may be less likely than their sedentary peers to become overweight. Caloric restriction in overweight persons produces larger weight losses than does exercise, although more of the weight loss by dieting is from lean body mass. The addition of exercise to diet intervention produces more weight loss than does dieting alone. Exercise has a favorable effect on body fat distribution, with a reduction in waist-to-hip ratio with increased exercise. Exercise is especially important in maintaining weight loss in overweight persons. Several prospective studies have shown that overweight men and women who are active and fit have lower rates of morbidity and mortality than overweight persons who are sedentary and unfit. Therefore, exercise is of benefit to overweight persons, even if it does not make them lean. Exercise is recommended as an important part of a weight control program. PMID- 8363202 TI - Use and abuse of appetite-suppressant drugs in the treatment of obesity. AB - Most of the available appetite-suppressant drugs act on noradrenergic and possibly dopaminergic receptors to produce satiety. A smaller number increase excess neuronal serotonin levels by blocking serotonin reuptake or by increasing its release. All these drugs produce significantly greater weight loss than does placebo in most studies. Abuse is a problem with amphetamine, methamphetamine, and benzphetamine, whereas other drugs have minimal or no potential for abuse. Weight loss can be sustained for up to 36 months. Net weight loss, compared with placebo, ranges from 2 to 10 kg, and weight regain after terminating drug treatment proves that drugs do not work when not taken. The stigma of obesity, the public opprobrium toward obese persons, and regulatory rigidity have led to unjustified distrust in the potential of drug treatment for obesity. PMID- 8363203 TI - Comparison of medically supervised and unsupervised approaches to weight loss and control. AB - The rising incidence of obesity in the United States has given physicians an increased role in its treatment. Although unsupervised programs can produce significant weight losses, the lack of medical supervision increases the potential for health problems. As with other lifestyle changes (for example, smoking cessation and blood pressure control), even minimal physician involvement may enhance outcome. In published clinical trials, the absence of contact with health professionals among control group participants may account in part for their poor success at weight loss or for their weight gain. Smaller trials examining the value of physician advice and encouragement among dieting patients have shown promising results. Physicians should monitor the health of obese and overweight patients during and after weight loss as is appropriate for the patient, depending on caloric levels, rate of weight loss, weight-loss goals, and intercurrent health events. Medical supervision is necessary for patients on very low-calorie diets, for severely obese patients (body mass index > 35), and for patients with other health problems. PMID- 8363204 TI - Minnesota studies on community-based approaches to weight loss and control. AB - Community-based approaches to weight control including worksite interventions, intervention by home correspondence, and multimodal community strategies are reviewed. Community-based programs have shown the ability to treat large numbers of obese persons, many of whom probably would not spontaneously seek professional care. Community-based approaches produce modest weight losses at lower costs than do clinical interventions. Although no community program has yet to reduce the prevalence of obesity in the general population, this area is relatively new and deserves further study. Recommended areas for future research include strategies for recruitment to community programs and primary prevention of weight gain. PMID- 8363205 TI - Short-term medical benefits and adverse effects of weight loss. AB - Weight loss reduces many of the health hazards associated with obesity including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, sleep apnea, hypoxemia and hypercarbia, and osteoarthritis. Potential adverse effects of weight loss include a greater risk for gallstone formation and cholecystitis, excessive loss of lean body mass, water and electrolyte problems, mild liver dysfunction, and elevated uric acid levels. Less consequential problems such as diarrhea, constipation, hair loss, and cold intolerance may also occur. The short term adverse effects are not severe enough to contraindicate weight loss, nor do they outweigh its short-term benefits. PMID- 8363206 TI - Relation of dieting and voluntary weight loss to psychological functioning and binge eating. AB - Voluntary weight loss in obese patients consistently reduces negative emotions such as depression and anxiety in the short term. Dieting by persons of normal weight is associated with low self-esteem and depressive symptoms. Dieting is linked to the development and maintenance of eating disorders such as anorexia nervosa and bulimia nervosa, although the precise nature of this association is unclear. Dieting cannot be a sufficient causal condition and must combine with other still undetermined vulnerabilities to cause eating disorders. Identification of these risk factors must precede the development of effective programs to prevent eating disorders. PMID- 8363207 TI - The association between weight loss and increased longevity. A review of the evidence. AB - Six published observational epidemiologic studies have reported evidence of reduced mortality rates in persons who have lost weight. In two studies, the reported protective effects of weight loss on mortality could not be justified by the data. In two other studies, weight loss was associated with both increased and decreased longevity in different subgroups. Only one study provided information on whether the weight loss was voluntary, but this study found similar effects of weight loss regardless of volition. These studies provided only limited information on the magnitude of weight loss associated with changes in longevity and no information on the types of methods used to achieve weight loss. Because of difficulties in studying long-term health outcomes related to obesity treatment, randomized, controlled trials are unlikely to provide a practical study design for this issue. Properly designed observational studies will probably provide the most useful information on the effects of voluntary weight loss on longevity. PMID- 8363208 TI - Long-term effects of change in body weight on all-cause mortality. A review. AB - OBJECTIVE: To summarize published studies analyzing the effects of long-term change in body weight on all-cause mortality and have not been reported elsewhere in these proceedings. DATA SOURCES: Thirteen reports from 11 diverse population studies, 7 from the United States and 4 from Europe. STUDY SELECTION: All studies included a weight change period of 4 or more years, followed by a mortality assessment period of 8 or more years. All weight changes occurred in persons 17 years or older. DATA EXTRACTION: Data from individual studies are presented as number of participants, number of deaths, ages at initial and final weight measurements, duration of the mortality follow-up period, consideration of cigarette smoking and other potential confounders, exclusion criteria, temporal separation between the weight change and mortality follow-up periods, and the association between weight change and all-cause mortality. DATA SYNTHESIS: Results are summarized by weight change associated with the lowest mortality rate and by the effects of long-term weight loss on mortality rate. CONCLUSIONS: Despite the diversity of the populations studied, the degree of "clinical clean up" at entry, the techniques used to assess weight change, and the differences in analytic techniques (including consideration of potentially confounding variables), certain conclusions may be drawn. Evidence suggests that the highest mortality rates occur in adults who either have lost weight or have gained excessive weight. The lowest mortality rates are generally associated with modest weight gains. PMID- 8363209 TI - Weight loss and subsequent death in a cohort of U.S. adults. AB - OBJECTIVE: Because we previously found that weight loss was associated with increased risk for death in all but very overweight men in a cohort of U.S. adults, we undertook a new analysis to determine whether inadequate control for preexisting illness or cigarette smoking contributed to this association. DESIGN: Cohort study. SETTING: The first National Health and Nutrition Examination Survey (NHANES I, 1971 to 1975) collected information on maximum lifetime weight and measured current weight on a probability sample of U.S. adults. The NHANES I Epidemiologic Follow-up Study determined the vital status of participants through 1987. PARTICIPANTS: Men (n = 2453) and women (n = 2739) who were 45 to 74 years old at the time of the NHANES I examination. RESULTS: The effect of excluding persons who died within the first 5 and first 8 years after baseline was examined to limit the influence of weight loss due to preexisting illness. For women, extension of the exclusionary period weakened the association between weight loss and increased risk for death from noncardiovascular disease. However, excluding death for as much as 8 years after baseline did not affect the strong association between weight loss and increased risk for death from cardiovascular disease among men and women with maximum body mass indexes between 26 and 29 (relative risks of up to 2.1 and 3.6 for men and women, respectively, after excluding deaths in the first 8 years). Results were not substantially altered by limiting the analysis to persons who never smoked. CONCLUSIONS: Preexisting illness may influence the association between weight loss and death principally through deaths from noncardiovascular disease. For some persons, weight loss is associated with an increased risk for death, even after excluding deaths occurring in the first 8 years. PMID- 8363210 TI - Body weight change, all-cause mortality, and cause-specific mortality in the Multiple Risk Factor Intervention Trial. AB - OBJECTIVE: To evaluate the relation between weight variability and death in high risk, middle-aged men participating in the Multiple Risk Factor Intervention Trial (MRFIT). DESIGN: Cohort study with 3.8 years of follow-up. SETTING: Multicenter, collaborative, primary prevention trial conducted at 22 clinical centers in the United States. PARTICIPANTS: Men (n = 10,529) who were 35 to 57 years old at baseline and who were in the upper 10% to 15% of risk for coronary heart disease because of smoking, high blood pressure, and elevated cholesterol level. Participants were seen at least annually for 6 to 7 years for medical evaluations in study clinical centers. MEASUREMENTS: Death from cardiovascular disease (228 deaths) and from all causes (380 deaths). RESULTS: The primary measure of weight variability was the intrapersonal standard deviation of weight (ISD), which was calculated from measured weights obtained at clinic visits during a 6- to 7-year period. All-cause death rates per 1000 person-years of follow-up across ISD quartiles were 8.28, 8.25, 10.57, and 11.07 from the first to fourth quartiles, respectively. After adjusting for baseline risk factors associated with weight change, the relative risk for all-cause mortality in the fourth compared with the first quartile was 1.64 (95% CI, 1.21 to 2.23). Cardiovascular death and ISD showed a similar pattern. The association between weight change and death was not observed in the heaviest men. CONCLUSION: Greater weight variability was associated with a greater risk for cardiovascular disease and all-cause mortality in some types of high-risk men. PMID- 8363211 TI - Benefits and adverse effects of weight loss. Observations from the Framingham Study. AB - OBJECTIVE: To identify the benefits and adverse effects of weight loss. DESIGN: Longitudinal, epidemiologic study in a defined population. PARTICIPANTS: Men and women (n = 2500) who were between 35 and 54 years old at baseline, followed for 20 years in Framingham, Massachusetts. MEASUREMENTS: Height, weight, lipid levels, blood pressure, smoking status, diet, physical activity, prevalent and incident cardiovascular disease, diabetes, other diseases, and mortality rate were assessed. RESULTS: Compared with those whose body mass index (BMI) or weight changed least, men and women who lost weight during a 10-year period were older, heavier, and had higher blood pressures and cholesterol levels initially but had the smallest gains in blood pressure and cholesterol levels. However, rates of cigarette smoking were higher, and rates of smoking cessation were lower. During 20 years of further follow-up, death rates were highest in those whose BMI decreased and in those with the highest BMI at study entry. Relative risks for death from cardiovascular disease, coronary heart disease, and all causes were significantly greater by 33% to 61% in men whose BMI decreased after adjusting for age and risk factors for cardiovascular disease. In women, weight loss and weight gain were associated with higher relative risks for cardiovascular disease and coronary heart disease, but only the 38% increase in total mortality rate among women who lost weight was statistically significant after adjusting for age. CONCLUSIONS: Weight loss was associated with improvements in blood pressure and cholesterol levels but also with continued cigarette smoking, prevalent and incident cardiovascular disease, diabetes mellitus, other diseases, and higher death rates. Leanness and maintenance of stable weight were beneficial to risk factors, and to the prevention of morbidity, and death. PMID- 8363212 TI - Methods for voluntary weight loss and control. NIH Technology Assessment Conference Panel. Consensus Development Conference, 30 March to 1 April 1992. AB - One quarter to one third of Americans are overweight; as many as 40% of women and 24% of men are trying to lose weight at any given time; many have tried a variety of methods, such as diets, exercise, behavior modification, and drugs. In controlled settings, participants who remain in weight loss programs usually lose approximately 10% of their weight. However, one third to two thirds of the weight is regained within 1 year, and almost all is regained within 5 years. For many overweight persons, achieving and maintaining a healthy weight is a lifelong challenge. Successful weight loss improves several cardiovascular risk factors and diabetic control; effects on mortality are not clear. Several epidemiologic studies have found that weight loss is associated with increased mortality but the reasons for weight loss were not known. Survey data also confirm that many Americans who are not overweight, particularly young women, are trying to lose weight, which may have adverse physical and psychological consequences. Because of the importance of these issues, research on weight and on weight loss and control should assume a high priority on the nation's health agenda. PMID- 8363213 TI - Immunomodulating drugs: major advances in research and development. PMID- 8363214 TI - Rapamycin's inhibition of thymocyte proliferation, unlike that of cyclosporin A or prednisolone, is not associated with cytotoxicity. PMID- 8363215 TI - Rapamycin inhibits lymphocyte proliferation in a popliteal lymph node model via an IL-2-independent mechanism. PMID- 8363216 TI - Rapamycin in a porcine renal transplant model. PMID- 8363217 TI - Synthesis and background chemistry of 15-deoxyspergualin. PMID- 8363218 TI - 15-Deoxyspergualin, a novel immunosuppressive drug: studies of the mechanism of action. PMID- 8363219 TI - Successful treatment with a novel immunosuppressive agent, deoxyspergualin, in type II collagen-induced arthritis in mice. PMID- 8363220 TI - Preclinical studies with 15-deoxyspergualin in various animal models for autoimmune diseases. PMID- 8363221 TI - 15-Deoxyspergualin: a novel immunosuppressive drug with clinical potential. AB - The studies discussed in this review suggest that DSG is a potent immunosuppressive agent, with at least some of its activity due to its direct effects on macrophages and B cells. The effects of DSG on macrophages include inhibition of IL-1, chemiluminescence, expression of MHC Class I antigen on the surface, and development of MAF. The agent may well interfere with antigen processing and the discovery of its binding to the heat-shock protein 70 may shed some light on this area. The effects of DSG on B lymphocytes include inhibition of surface Ig expression and B cell differentiation. In addition, however, DSG exhibits some effects on both B and T lymphocytes and is markedly active in blocking both the primary and secondary cytotoxic T cell and antibody-producing cell generation. The agent is relatively nontoxic at the doses in which it exerts these marked effects. Thus, an overall assessment of DSG shows that it may provide immune suppression at levels different from those of immunosuppressive agents already available. Advances in human organ transplantation have for the most part occurred stepwise with the introduction of progressively improved techniques of immunosuppression. Tissue-matching, organ preservation, techniques of transplantation, and surgical post-operative care of organ transplant recipients have all improved over the 30 years since organ transplantation began, but have not been the major factors in the improved survival of both patients and grafts seen at the present time. The initial advance in immunosuppression which made the first organ transplants possible was the finding of the immunosuppressive capabilities of azathioprine (Imuran) and the ability to reverse acute rejection crisis with prednisone. Anti-thymocyte or anti-lymphocyte globulin, introduced in 1966, achieved variable results, with some groups reporting excellent patient and graft survival using this agent. Others using different variations of this drug showed no improvement in results. By the mid 1970s, transplant results had improved at a number of units, with graft survivals of kidney and heart recipients in the 70 percent range at 1 to 2 years. No major progress was reported in most units, however, until the introduction in 1978 of cyclosporine. A major effect of cyclosporine was to create a universal improvement in graft survival in all units surveyed around the world with a 70 to 75 percent one-year cadaver kidney graft survival, representing the basic standard for clinical results.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8363222 TI - Deoxyspergualin in allogeneic kidney and xenogeneic islet transplantation: early clinical trials. PMID- 8363223 TI - Deoxyspergualin: clinical trials in renal graft rejection. Japan Collaborative Transplant Study of Deoxyspergualin. AB - The percentage of efficacy of DSG, when used alone, was 76 percent in patients having acute rejection within 6 months after grafting. The doses of 3 to 5 mg/kg/day was judged to be recommendable and the duration of treatment of 7 days was evaluated as a suitable duration. Rescue use of DSG was effective in 70 percent of patients having MP-resistant rejection. In acute rejection, the percentage of efficacy of DSG plus MP combination was 88 percent. In addition, we should note that the percentage of efficacy of DSG was 66 percent even in acute or chronic rejection. The main adverse reactions with DSG included a sensation of numbness of the face, lips, and limbs, gastrointestinal troubles, and bone marrow suppression, but these adverse reactions were not serious. DSG has a mechanism of action different from that of other immunosuppressive agents, and it has fewer adverse effects than other drugs. Different from biological preparations, DSG is a strong immunosuppressive agent that can be used repeatedly. PMID- 8363224 TI - A member of the Hsp70 family of heat-shock proteins is a putative target for the immunosuppressant 15-deoxyspergualin. PMID- 8363225 TI - Effects of 15-deoxyspergualin on the expression of surface immunoglobulin in 70Z/3.12 murine pre-B cell line. PMID- 8363226 TI - Guanine arabinoside as a bone marrow-purging agent. AB - Arabinosylguanine (araG) is a nucleoside analogue that is rapidly converted by cells of the T lymphoid lineage to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and selective in vitro toxicity to T lymphoblastoid cell lines as well as to freshly isolated leukemia cells from patients with T cell acute lymphoblastic leukemia (ALL). We have previously demonstrated that araG is an effective agent to use for chemoseparation of malignant T lymphoblasts from human bone marrow. When freshly isolated human T leukemia cells or T lymphoblastoid cells were treated with 100 microM araG for 18 hours, up to 6 logs of clonogenic T cells are eliminated without appreciable toxicity to the normal myeloid, erythroid, and megakaryocytoid clonal progenitor cells. We subsequently described studies in a murine model of T cell acute lymphoblastic leukemia (ALL) in which we tested whether bone marrow contaminated with malignant T cells and purged ex vivo with araG, could reconstitute both the lymphoid and myeloerythroid lineages in the absence of leukemic relapse. The model utilized 6C3HED tumor cells, derived from a Thy 1.2+ malignant murine T cell line, which were shown to cause lethal leukemia in C3H/HeN mice. Intravenous injection of 10(6) 6C3HED cells resulted in 100 percent mortality within 18 days, with autopsy revealing tumor infiltration of multiple organs. Evidence of araG's ability to purge bone marrow of malignant tumor cells without causing significant toxicity to normal marrow-derived hematopoietic progenitor cells was documented in experiments in which 75 percent of lethally irradiated mice receiving transplants of syngeneic bone marrow contaminated with 6C3HED tumor cells and treated ex vivo with 100 mM araG for 18 hours survived for 250 to > 400 days. Reconstitution of the lymphoid, myeloid, and erythroid lineages with donor cells in surviving mice was documented. The data presented indicate that araG may effectively purge bone marrow of malignant T cells without irreversible toxicity to hematopoietic stem cells. This purging regimen is recommended for consideration for clinical trials in patients with T cell malignancies undergoing autologous bone marrow transplantation and may also be a viable option for T cell depletion as a strategy to prevent graft versus host disease. PMID- 8363227 TI - Application of X-ray crystallographic methods in the design of purine nucleoside phosphorylase inhibitors. PMID- 8363228 TI - Activities of two 9-deazaguanine analogue inhibitors of purine nucleoside phosphorylase, CI-972 and PD 141955, in vitro and in vivo. PMID- 8363229 TI - Levamisole-induced neopterin synthesis. PMID- 8363230 TI - Recent clinical trials with levamisole. PMID- 8363231 TI - Sex hormones as immunomodulators of disease. PMID- 8363232 TI - Corticosteroids as immunomodulators. AB - Corticosteroids are potent anti-inflammatory and anti-immunologic modulators. They interact with cellular receptors, which eventually leads to modification of DNA transcription. These changes sometimes inhibit cell function and sometimes increase production of cell products. A number of effects are seen throughout the organism, leading to downregulation of allergic responses, inhibition of cell mediated immunity, decreased accumulation of inflammatory cells, and a lessening of proinflammatory stimuli and blood-vessel responses. PMID- 8363233 TI - Overview on the chemistry and immunomodulating properties of novel pyrimidinones. PMID- 8363234 TI - Bropirimine in bladder cancer: clinical studies. PMID- 8363235 TI - Immunosuppressive activity of mycophenolate mofetil. PMID- 8363236 TI - Study of the immunosuppressive properties of cyclosporine analogues. PMID- 8363237 TI - Suppression of alloantigen presentation by prodigiosin, a T cell-specific immunosuppressant. PMID- 8363239 TI - Syntheses of macromolecular immunomodulators and conjugates employing haloacetyl reagents. PMID- 8363238 TI - In vivo antitumor activity of the hypoxanthine derivatives ST 789 and ST 689. PMID- 8363240 TI - Immunomodulating activity of myelopeptides: clinical trials. AB - Bone marrow cells of various animal species and the human produce a group of bioregulatory peptides called myelopeptides (MPs). A highly purified myelopeptide (MP) fraction and some individual molecules have been isolated from the supernatant of the porcine bone marrow cell culture by successive gel chromatography and HPLC. Myelopeptides have a wide spectrum of functions including immunoregulatory, differentiating, and opiate-like activities. A new immunoreactive drug, Myelopidum, has been created on the basis of myelopeptides. This drug is effectively used in Russian medicine for treating diseases accompanied by immunodeficiency and in veterinary practice for prophylaxis and treatment of newborn and young animals with such diseases as pneumonia and enteritis. Treatment of patients by Myelopidum after major surgery prevents 50 to 70 percent of postsurgical complications, particularly postsurgical pneumonia. Myelopidum normalizes the number and balance of T helper and T suppressor cells and B lymphocytes in patients with chronic pulmonary diseases and promotes the beneficial clinical effect of significant prolongation of periods of remission. PMID- 8363241 TI - Structural nature and functions of transfer factors. AB - Transfer factors are molecules that "educate" recipients to express cell-mediated immunity. This effect is antigen-specific. The most consistent effects of transfer factors on the immune system are expression of delayed-type hypersensitivity and production of lymphokines such as macrophage migration inhibitory factor (MIF), which is probably identical to gamma-interferon in response to exposure to antigen. Transfer factors bind to antigens in an immunologically specific manner. This discovery has enabled us to isolate individual transfer factors from mixtures that contain several transfer factors. This reactivity probably explains the specificity of individual transfer factors, and it has provided a method for purification of individual transfer factors to apparent homogeneity. The purified materials are immunologically active and antigen-specific. They have molecular weights of approximately 5,000 Da and appear to be composed entirely of amino acids. Transfer factors appear to offer a novel means of molecular immunotherapy for certain patients with defective cell mediated immunity. PMID- 8363242 TI - Effect of oral administration of heat-killed Enterococcus faecalis FK-23 on the leukocyte-reconstituting capacity in immunosuppressed dogs. PMID- 8363243 TI - Antitumor and antimicrobial activities of enterococcal preparation orally administered to mice. PMID- 8363244 TI - Immunostimulating peptide derived from soybean protein. PMID- 8363245 TI - Two simple glucose derivatives with opposite immunoactivities. PMID- 8363246 TI - Immunopharmacologic study of glucofructan from Symphytum asperum roots. PMID- 8363247 TI - The Edward Jenner Lecture. Biological spinoffs of organ transplantation. PMID- 8363248 TI - The George Hitchings and Gertrude Elion Lecture. The pharmacology of azathioprine. PMID- 8363249 TI - The Gerhard Domagk Lecture. Transcription factors in lymphoid development. PMID- 8363250 TI - Immunomodulating drugs: whence and whither. PMID- 8363252 TI - Immunomodulating activity of antifungal drugs. AB - 1. The immunomodulating activity of antifungal drugs was reviewed. Although results are conflicting, all azole drugs tend to be immunosuppressive, except for fluconazole, which has no immunologic effect. In contrast, the polyene antibiotic amphotericin B (AMPH) is immunostimulatory. 2. AMPH induced host resistance to Pseudomonas aeruginosa infection in mice, whereas no azole drugs did so. 3. Polymorphonuclear leukocytes are activated by AMPH, but not by any azole drugs, in terms of the level of their adherence. 4. No azole drugs induce in vitro tumor necrosis factor alpha (TNF) production by macrophages, whereas AMPH slightly but substantially does so. 5. AMPH potently primes macrophages in vitro and in vivo so that they produce large amounts of TNF after the secondary stimulation (triggering) by bacterial lipopolysaccharides or a streptococcal preparation used for antitumor immunotherapy, OK432. 6. Viable or heat-killed Candida albicans cells are capable of inducing in vitro TNF production by macrophages. This activity of the fungal cells is enhanced by AMPH. PMID- 8363251 TI - Immunomodulator effects on the Friend virus infection in genetically defined mice. AB - The disease induced by the Friend virus complex (FV) in F1 hybrid mice containing the Rfv-3r/s genotype in the presence of H-2a/a was used to evaluate a variety of immunomodulating substances. In these genetically defined mice, the FV disease results in splenomegaly, early production of high titers of cell-associated and plasma virus, high levels of splenic viral RNA, increased hematocrit, and eventual death. As the disease progresses, reduced levels of infectious virus correlate with development of specific antibody; reduction in T cell populations, increase in B cells, and decrease in T-cell function also occur. The following immunomodulators were evaluated, listed in the order of their ability to inhibit the FV disease: imexon > MVE-2 > human recombinant IFN-alpha A/D > AS101 > ampligen > AM-3 = oxamisole > ImuVert > bropirimine. In fact, bropirimine, used with certain treatment regimens, appeared to enhance the FV disease. These data suggest that certain immunomodulators may have potential value in the treatment of HIV disease, but also indicate that caution should be exercised in their clinical use. PMID- 8363253 TI - Immunopharmacologic properties of inosine 5'-methyl monophosphate (MIMP). PMID- 8363254 TI - Immunomodulatory properties of AZT. PMID- 8363255 TI - Antiviral activity of a synthetic double-stranded polyribonucleotide interferon inducer in a murine AIDS retrovirus model. Role of augmentation of natural killer cell activity and synergy with oral AZT. PMID- 8363256 TI - Modulation of cytokine responses in sepsis. PMID- 8363257 TI - Interventions for the treatment of septic shock. PMID- 8363258 TI - Pleiotropic effects of transforming growth factor-beta on cells of the immune system. AB - It is now apparent that the TGF-beta has potent immunoregulatory properties. Although most reports have described the immunosuppressive activities of TGF beta, recent evidence supports the concept that TGF-beta can have both inhibitory and stimulatory actions. The delivery of sufficient quantities of TGF-beta has proven beneficial in several disease models such as allograft rejection and autoimmunity. Moreover, the increased levels of TGF-beta found in several disease states associated with immunosuppression suggests that inhibitors of TGF-beta may be clinically useful in some diseases. Thus, TGF-beta or antagonists to TGF-beta have exciting potential for use in treating or preventing several diseases (Table 6). PMID- 8363259 TI - Cytokines and modulation of diseases of immediate hypersensitivity. PMID- 8363260 TI - Therapeutic peptides that block interaction of T cells with MHC in experimental allergic encephalomyelitis. PMID- 8363261 TI - Antigen presentation by the murine renal proximal tubule: a mechanism of self tolerance? PMID- 8363262 TI - Immunologic aspects of kampo medicine. PMID- 8363263 TI - Inhibition of hypersensitivity reactions by saiboku-to (TJ-96), particularly on type IV reaction. PMID- 8363264 TI - Effect of an herbal preparation, saiboku-to (TJ-96), on antigen-induced airway hyperresponsiveness and eosinophil infiltration in actively sensitized guinea pigs. off. PMID- 8363265 TI - Effects of saiboku-to (TJ-96) on the production of platelet-activating factor in human neutrophils. AB - Platelet-activating factor (PAF) has been recognized as an important chemical mediator in allergic and inflammatory reactions. Evidence suggests that PAF is deeply involved in the pathogenesis of bronchial asthma, in which PAF induces profound bronchospasms, increased vascular permeability, and eosinophil/neutrophil accumulation in the respiratory tract. The precise pharmacologic mechanisms of Kampo preparations are still obscure, but extensive experience has established their clinical effectiveness for the treatment of patients with allergic and inflammatory disorders. We tried to examine the effects of Saiboku-to (TJ-96), a Kampo prescription, on in vitro PAF production by human neutrophils because this preparation is widely used for the management of patients with bronchial asthma and bronchitis. Saibokuto inhibited in vitro PAF production in a dose-dependent manner. Among the major natural components of Saiboku-to, saiko (Bupleuri radix) and kanzo (Glycyrrhizae radix) showed inhibitory effects on PAF production, whereas ohgon (Scutellariae radix) had no inhibitory effect. Saikosaponin a and c, purified elements extracted from saiko, showed no inhibitory effects, but saikosaponin d and glycyrrhizin, extracted from kanzo, inhibited PAF production dose-dependently. Further studies are needed to evaluate the clinical significance of Kampo medicines in allergic diseases, but our present results suggest that the pharmacologic benefit of Saiboku-to is partially due to its inhibitory effect on PAF production. PMID- 8363266 TI - Rapamycin: in vitro profile of a new immunosuppressive macrolide. PMID- 8363267 TI - A multicenter clinical trial of TJ-96 in patients with steroid-dependent bronchial asthma. A comparison of groups allocated by the envelope method. PMID- 8363268 TI - Cytokines and their role as growth factors and in regulation of immune responses. PMID- 8363270 TI - The role of the T cell receptor alpha chain in antigen-specific immune suppression. PMID- 8363269 TI - The interleukin-2 receptor: a target for immunotherapy. PMID- 8363271 TI - Autoantibodies against cytochromes P-450 in drug-induced autoimmune hepatitis. PMID- 8363272 TI - Immunity to halothane metabolite-modified proteins in halothane hepatitis. PMID- 8363273 TI - Effects of small doses of dioxins on the immune system of marmosets and rats. AB - There is no doubt that TCDD is capable of inducing effects on a variety of components and functions of the immune system in a variety of species. In fact, such changes seem to belong to the most sensitive variables affected by TCDD. Some of the biological effects, induced at rather high doses of TCDD exhibiting general toxicity (> 3 micrograms TCDD/kg body wt), may be considered unspecific or the result of the pronounced thymus involution. However, other effects (such as that on lymphocyte subtype patterns in marmosets or a reduced resistance of mice to influenza viruses) have been reported to occur at dose levels far from those leading to thymic involution or general toxicity. It should be remembered that the pathognomonic relevance for man of subtle modifications in the pattern of lymphocyte surface receptors is largely unknown. Until now, such deviations are considered rather as biological phenomena than indications or causes of specific diseases. Nevertheless, such changes represent clear-cut biological effects induced by TCDD. Since effects of TCDD on components and defined functions of the immune system have been revealed in several species, it would be surprising if humans were largely resistant to such effects, but reliable data in humans with high exposures to defined dioxins verified by an appropriate quantification of the exposure are scarce as of now. Data published so far have not revealed pronounced alterations of such variables. However, no studies of well-defined human populations with quantified body burdens have been performed with modern methods (such as flow cytometry) analyzing a wide variety of surface receptors. Performance of such studies is essential for a better and reliable risk assessment, and the technology is available. Some of the effects observed (such as the changes in the pattern of lymphocyte subpopulations) must certainly be considered as biological effects induced by TCDD, and the situation is similar to the induction of hepatic monooxygenases, which are also observable in this dose range. However, the relevance of such changes with respect to adverse health effects in humans is presently difficult to judge in the absence of clear-cut functional deficits demonstrated so far either in vivo or in vitro. PMID- 8363274 TI - Prevention and treatment of allograft rejection in vivo by rapamycin: molecular and cellular mechanisms of action. PMID- 8363275 TI - Immunologic approaches to the therapy of HIV-1 infection. PMID- 8363276 TI - Gene transfer for therapy and prophylaxis of HIV-1 infection. PMID- 8363277 TI - Modulation of macrophage function by transforming growth factor beta, interleukin 4, and interleukin-10. AB - The findings reviewed above leave no doubt as to the complexity of actions of TGF beta, IL-4, and IL-10 on monocytes/macrophages. Along with MDF, whose actions were recently reviewed elsewhere, TGF-beta, IL-4, and IL-10 are the only presently known, purified cytokines that have been shown to have strong macrophage-deactivating effects. However, none of them can be categorized as purely macrophage deactivating since they also exert macrophage-activating effects. In vitro, their effects, both in terms of extent and direction (activating vs. deactivating), are strongly influenced by the stimulation conditions (e.g., triggering signal, cytokine concentration, timing of cytokine addition), the species (mouse vs. human), the source (blood vs. peritoneal, alveolar, colostral) and the state of differentiation/activation of the macrophage (e.g., resting vs. inflammatory). In addition, TGF-beta, as well as IL 4 and IL-10, up- and/or downregulates the function of several cell types other than macrophages, which further hampers our ability to predict, on the basis of in vitro experiments with macrophages, possible effects during an immune response in vivo. Despite this complexity, the highly reductive approach of in vitro studies has revealed important differences in the ability of TGF-beta, IL-4, and IL-10 to modulate the phenotype of monocytes/macrophages. The disparities have been most striking with regard to the secretory function of monocytes/macrophages (see Table 2). First, TGF-beta, IL-4, and IL-10 have a different spectrum of activity. Thus, TGF-beta, but not IL-4 or IL-10, can induce resting human monocytes to produce TNF, IL-1, and IL-6. Second, they affect monokine and RNI and ROI production to a different extent. For example, IL-10 is an approximately 25-fold more potent suppressor of LPS-induced TNF production by mouse macrophages than is TGF-beta. Third, they differ in their ability to overcome additional activating stimuli, so that in the presence of LPS, IL-4, but not TGF-beta or IL 10 suppresses IFN gamma-induced RNI release. Fourth, their macrophage deactivating effects require different stimulation conditions. Thus, IL-4, but not TGF-beta, interferes with RNI release strongly only after preincubation of the macrophages. Finally, these agents deactivate macrophages by distinct mechanisms. For example, IL-10 causes massive downregulation of TNF mRNA, whereas TGF-beta suppresses TNF release on a translational level. It will be a challenge to define clinical applications for these potent macrophage modulators on the basis of their different spectrum of activities. For TGF-beta and IL-4 such studies have already been initiated. PMID- 8363278 TI - Rapamycin prolongs survival of murine recipients of fully allogeneic donor grafts when administered during the graft-versus-host disease process. PMID- 8363279 TI - Pseudomonas exotoxin and recombinant immunotoxins derived from it. AB - Pseudomonas exotoxin (PE) is a bacterial toxin that kills mammalian cells by gaining entry to the cytosol and inactivating protein synthesis. The toxin binds and enters cells via the alpha 2-macroglobulin receptors. Within cells, the toxin is processed in several steps to produce an enzymatically active 37-kDa C terminal fragment which translocates to the cytosol and ADP-ribosylates elongation factor 2. Because PE is a very potent toxin, derivatives of it have been produced which, when joined to various binding ligands, are capable of killing specific target cells. It is hoped that this strategy will lead to the development of effective therapeutic agents for the treatment of human diseases such as cancer, AIDS, and various immunologic disorders. PMID- 8363280 TI - Superantigens in infectious diseases, including AIDS. PMID- 8363281 TI - RNA drug therapy acting via the 2-5A synthetase/RNase L pathway. PMID- 8363282 TI - Specific RNA drug therapy of hepatitis viruses. PMID- 8363283 TI - Quantitative determination of HLA-DR antigen expression on cell surfaces with monoclonal antibody by Dot-ELISA. PMID- 8363284 TI - Immunosuppressive effects of lymphocyte-specific histamine congener treatment of an adoptive transfer model. PMID- 8363285 TI - Issues in the development of a prophylactic HIV vaccine. PMID- 8363287 TI - Vaccines based on synthetic polyions and peptides. PMID- 8363286 TI - T cell vaccines for autoimmune diseases. PMID- 8363288 TI - Advances in influenza virus vaccine research. AB - Influenza epidemics occur annually in the United States and are characterized by high frequencies of illness among children and young adults, high hospitalization rates among infants and older persons, and high death rates among the elderly. Vaccines that can prevent infection must stimulate anti-hemagglutinin antibody in serum and secretions; those that stimulate anti-neuraminidase antibody or T cell cytotoxic responses can reduce the severity of infection and illness or hasten recovery. Advances in vaccine research are permitting evaluation of pure subunit vaccines, new adjuvants, topical immunization, and the use of immunomodulators for enhancing immune responses. In young adults, doses of HA of up to 405 micrograms were well tolerated and provided enhanced antibody responses. Although use of a muramyl-dipeptide derivative as an adjuvant resulted in unacceptable reactogenicity, other adjuvants may be acceptable. Development of topical immunization and immunomodulators are under way. The cold-adapted live attenuated influenza virus vaccines for nasal administration are nearing availability. They are safe, immunogenic, and protective with greatest effectiveness among young children, in whom inactivated vaccines are less useful. Use among children should moderate the high frequencies of illness and hospitalization in this group and reduce spread of influenza in the community. CRV also provide an alternative to inactivated vaccines among young adults, in whom they can be equally protective. PMID- 8363289 TI - Effects of orally administered rapamycin in animal models of arthritis and other autoimmune diseases. PMID- 8363290 TI - The effects on pupil size and accommodation of sympathetic and parasympatholytic agents. AB - The time-response effect of two currently used mydriatics, phenylephrine and tropicamide, were evaluated in 524 eyes. Four different types of dilating regimens were used: 2.5% phenylephrine, 10% phenylephrine, 0.5% tropicamide, and the combination of 2.5% phenylephrine and 0.5% tropicamide. The analysis indicated that the recovery from mydriasis occurs between 5.5 and 7.0 hours with 2.5% phenylephrine and at more than 7 hours with 10% phenylephrine. The 0.5% tropicamide induced rapid dilation, whereas the combined treatment, 2.5% phenylephrine plus 0.5% tropicamide, produced the largest maximum pupillary diameter. Tropicamide, alone or in combination, also produced a longer mydriatic effect, lasting more than 7.0 hours. The recovery from the cycloplegic effect of the mydriatics occurred between five and seven hours in the majority of patients, with tropicamide alone or in combination with phenylephrine requiring the most time to revert to normal ranges of accommodation. The findings in this study indicate that, in normal subjects, the recovery from the effect of mydriatic agents is longer than what is generally reported in the literature. PMID- 8363291 TI - The effect of wrist rest, caffeine, and oral timolol on the hand steadiness of ophthalmologists. AB - Because hand steadiness is an important aspect of microsurgical technique, hand movement, amplified by a hand-held laser pointer, was measured in 14 ophthalmology trainees on four separate mornings when each had ingested (1) 200mg of caffeine, (2) 12.5mg of timolol (2.5mL of timolol 0.5% ophthalmic solution), (3) a combination of caffeine and the beta-adrenergic blocker, or (4) a placebo. Caffeine increased the resting pulse and hand movement. Although the beta adrenergic blocker and the combination of caffeine and this drug decreased the resting heart rate from that of placebo, they did not significantly change hand steadiness. However, compared with caffeine alone, the beta-adrenergic blocker caffeine combination significantly decreased hand movement and the pulse. Resting the wrist significantly steadied hand movements. Hand movement was not correlated with the level of ophthalmology training, the trainee's weight, or their daily caffeine consumption. PMID- 8363292 TI - Thirty years of cryoophthalmology. AB - Thirty years ago, the method of cataract cryoextraction was reported. The possibilities of low-temperature application in medicine were revealed and gave rise to the new branch of ophthalmology called cryoophthalmology. This article presents the development of this science, its achievements in ophthalmology, and the theoretic basis for using low temperatures in ocular diseases. Thirty years have passed, but cryoophthalmology still maintains its importance and usefulness, and many research centers all over the world are involved with it. PMID- 8363293 TI - Monolateral chorioretinitis with multiple foci in one case of Lyme disease. AB - Lyme disease involves numerous anatomic areas and systems and is caused by a spirochete, Borrelia burgdorferi. In this article, we describe one case of monolateral chorioretinitis with multiple foci in a 22-year-old myopic man. The diagnosis of this disease was confirmed by positive specific anti-B. burgdorferi antibodies titrated with an enzyme-linked immunosorbent assay method and by serum conversion occurring approximately six weeks after the end of therapy. Considering the potential effect of this disease on the world's population, we wish to draw attention to its occurrence because it frequently involves ocular structures. Prompt and adequate therapy guarantees complete healing and avoids both short- and long-term complications. PMID- 8363294 TI - Macular infarction after intravitreal amikacin. AB - A case of macular infarction after intravitreal amikacin was observed in a patient with postoperative endophthalmitis. A review of the literature revealed no previously documented case occurring after intravitreal amikacin. Suggestions to avoid such a complication in an otherwise recovered patient are discussed. Also, better alternatives to intravitreal aminoglycosides should be sought. PMID- 8363295 TI - Pseudoretinitis pigmentosa in patients with systemic lupus erythematosus. AB - A 42-year-old woman and a 62-year-old man with systemic lupus erythematosus (SLE) had bilaterally mottled retinas with spots or clumps of pigment. Their electroretinographic responses were subnormal. Their fundi resembled those of patients with retinitis pigmentosa. The fundus lesions of our patients may have resulted from vascular occlusion associated with SLE. PMID- 8363296 TI - Nonpenetrating trauma in the right eye induces anterior uveitis and secondary glaucoma in the contralateral eye. AB - A 31-year-old woman was shot with a toy bullet OD. Intracameral cells and fibrin were found, but no penetrating wound was noticed. Flare was observed in the left anterior chamber three days after the incident, and the intraocular pressure OS had increased. No specific type of uveitis or systemic inflammatory disease was identified. We believe that bilateral uveitis was precipitated in our patient by the nonpenetrating trauma. PMID- 8363297 TI - [Primary carcinoid of the larynx. Apropos of a case. Review of the literature]. AB - We report a new case of primary atypical carcinoid of the larynx. This rare neuro endocrine neoplasm of the larynx was initially mis diagnosed in 50% of the cases published. Since, characteristically these are lesions of the epilarynx causing dysphonia at early stages of development, the diagnosis should be kept in mind when the work-up for dysphonia reveals a small tumor of the epiglottis or aryepiglottic folds. The histological diagnosis should be oriented by Grimelius staining and confirmed immunoperoxidase marker studies for chromogranin and cytokeratin. Although, atypical carcinoids of the larynx are aggressive malignant tumors, the prognosis for early lesions of less than 1 cm is excellent. However, unlike early squamous cell carcinomas, these tumors do not respond well to radiation therapy. Primary surgery is the treatment of choice. PMID- 8363298 TI - [Cervical leiomyosarcoma. Apropos of a case and review of the literature]. AB - A case of leiomyosarcoma of the head and neck is presented together with a review of the literature. The histopathological diagnosis is difficult in spite of immunocytochemistry. Surgery is the therapy of choice. PMID- 8363299 TI - [Cervical cystic lymphangioma in adults]. AB - Cystic hygromas, infrequent in children, are even rarer in adults where they once were generally an unexpected operative findings. Now, with the progress in modern medical imaging the diagnosis can be suggested before operation. Analysis of the embryogenesis helps to explain the different anatomical and clinical forms and the relations of the cystic hygroma with neighboring tissues, particularly of renous origin, grases of cystic hygroma of the neck in adults are reported and discussed with 26 other well documented cases from the literature. The diagnosis can be confirmed only after operation and histological examination. Surgical removal is technically less difficulte in adults than in children and recurrences are rare. PMID- 8363300 TI - [A new approach to the mechanism of vestibular response to caloric stimulation]. AB - Barany's classical hydrodynamic theory has been called into question by the zero gravity Spacelab experiments, and several new hypotheses are put forth to explain the vestibular response to caloric stimulation. We have developed a mathematic model based on the analysis of an experimental model of the semicircular canal, incorporating observations done with zero-gravity and with gravity. Two purely mechanical phenomena are involved: one one hand, the modification of the hydrostatic pressure on both sides of the cupula due to a temperature variation if the semicircular canal is not in the horizontal plane in normal gravity conditions; on the other hand, local changes in endolymph pressure and volume due to the mechanical and osmotic properties of the canal, which are independent from gravity and from the position of the canal. These mechanical processes, though not exclusive, are predominant and therefore sufficient to explain the caloric response of the vestibulum in all cases. PMID- 8363301 TI - [Bacterial epidemiology of chronic otitis. Prophylactic and therapeutic deductions]. AB - Antimicrobial sampling was performed in the external auditory canal and in the mastoid cavity when possible in 80 middle ears operated on during the last 15 months. These samplings concerned 20 cholesteatomas. 25 suppurative chronic otitis, 25 non suppurative chronic otitis and 6 miscellaneous. In 20 out of 80 cases (25%), one or several microbial agents were identified: cholesteatomas (35%), suppurative chronic otitis (38%), non suppurative ones (4%) and miscellaneous (16%). In most cases a staphylococcus or a negative gram agent was sensitive to amoxycillin-clavulanique acid. When sampling was performed in the mastoid cavity, the agent was not sensitive to this antibiotic (80% of cases). This study demonstrates that a prophylactic therapy against aerobic and anaerobic agents is necessary in non suppurative chronic otitis whereas the antimicrobial therapy must be adapted in other pathologies. PMID- 8363302 TI - [Clinical evaluation of otolithic function by the measurement of ocular cyclotorsion and skew deviation]. AB - The ocular tilt reaction (OTR) consists in an association of an eye-head postural reaction, alteration of vertical perception, conjugated eye cyclotorsion, skew deviation and head tilt. We observed this condition following unilateral vestibular neurectomy and labyrinthectomy performed in patients suffering from severe Meniere's disease. All patients described postoperative vertical diplopia and vertical perception tilt. One illustrative case is reported in detail here. Changes in visual vertical were measured using a vertical frame with a pivoting pointer and the Maddox rod calibrated with a spirit level. The actual eye torsion was measured by a photography of eye-fundus. In the follow-up, it was found that vertical diplopia disappeared within a few days while conjugated eye cyclotorsion lasted weeks to months. Mechanisms involved in the OTR could be the consequence of a unilateral deafferentation of the utricular and saccular organs. We feel that the techniques of examination which we used with this patient might be a useful measurement for the clinical evaluation of unilateral otolithic dysfunction. PMID- 8363303 TI - [Diagnostic perspectives in rhinology]. AB - The physical evaluation of the nasal cavity and paranasal sinuses has been improved by recent advances in diagnostic endoscopic systems and computerized tomography. Today, nasal endoscopy is considered to be the only comprehensive diagnostic rhinoscopic examination and computerized tomography has replaced the standard plain film roentgenograms in the initial evaluation of the paranasal sinuses. Advances have also been made in the evaluation of nasal functions, particularly in the assessment of obstruction. Rhinomanometry is the only method of objective assessment of the patency of the nasal cavities and makes it possible to perform nasal provocation tests. Today, this method of exploration should not be overlooked. Secretory function may be assessed by various methods: nasal cytology, quantification of inflammatory mediators in nasal cavity washing, and biochemical analysis of nasal secretions (albumin/protein ratio). Mucociliary function can be evaluated by measuring the nasal mucociliary clearance, by determining the frequency of cilia strokes (after brushing of the nasal mucosa and microscopic examination under stroboscopic light) and by election microscopic ultra-structure studies. Other methods of exploration which do not yet have a practical application are currently being investigated: rheologic studies of the mucus, immunologic evaluation of nasal secretions and acoustic rhinometry. PMID- 8363304 TI - [Rhinosinusal manifestations of cystic fibrosis]. AB - The generalized disorders which characterize cystic fibrosis often involve the nose and paranasal sinuses and may frequently lead to the development of nasal polyps. A retrospective study of 78 patients with cystic fibrosis, 3 to 28 years old, was undertaken in order to determine the incidence of nasal involvement and to define an approach to the treatment of disabling recurrent nasal polyposis. 65% of these patients presented chronic symptoms such as rhinorrhea, nasal obstruction and disturbances of smell. Nasal polyps were found in 50% of patients and were more frequent in adults than in children. Clinical symptoms were directly related to the extent of polyp development which could be classified according to 3 groups. CT scans showed maxillary sinus involvement in almost all patients. The incidence and extent of ethmoidal sinus involvement on CT scans was correlated to the grade of polyp development. Medical treatment of polyposis failed in all cases. Polypectomy was always followed by recurrence. Intranasal ethmoidectomy seems to be an interesting alternative, since 73% of patients undergoing this procedure had clinical improvement. PMID- 8363305 TI - [Metastatic basal cell carcinoma]. AB - A case of basal cell carcinoma in a 17-year old male patient complicated, 5 years later, by inguinal and pulmonary metastases is reported. This clinical case raises two problems: the reality of the entity and the long-term follow-up of this type of tumours. PMID- 8363307 TI - [Value of methotrexate in a case of florid cutaneous sarcoidosis]. AB - The effectiveness of methotrexate against cutaneous sarcoidosis lesions resistant to corticosteroids or synthetic anti-malarial drugs has been reported by a few authors, and it is confirmed by the following case-report. A 54-year old woman had been suffering from sarcoidosis since 1977. Most of the lesions affected the skin and consisted of a very large plaque over the forehead and lesions on the elbow, forearm and knee. She also had Lofgren's syndrome stage II and Perthes Jungling osteitis. The highly inflammatory and extensive features of these lesions, and the patient's plea for treatment justified a systemic therapy. A first 4-day course of methylprednisolone succinate given as intravenous bolus injection was remarkably effective with collapse of the skin lesions, but these recurred about 4 months later. A second 4-day course of methylprednisolone was followed by an oral combination of mepacrine and chloroquine. Four years later, reactivation of the lesions required another course of corticosteroids given intravenously, then orally for a long time, but the use of these drugs in doses exceeding 30 mg per day, the poor results obtained and the appearance of diabetes mellitus made it necessary to discontinue this treatment. The patient was then put on methotrexate 10 mg per week. After 13 months, the results were dramatic, and the improvement observed has remained progressive and persistent. The drug was well tolerated, both clinically and biochemically. Although the skin lesions of sarcoidosis are innocuous, a treatment is indispensable in view of the major cosmetic damage inflicted on the patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363306 TI - [Oculocutaneous type II tyrosinosis]. AB - Richner-Hanhart syndrome, also called oculo-cutaneous tyrosinosis type II, is a recessive autosomal genodermatosis consecutive to a disorder of tyrosine metabolism. It presents as a varying association of palmo-plantar keratosis, bilateral keratitis and mental retardation. The authors report a new case which is atypical in that palmoplantar keratosis made a late appearance. The diagnosis was confirmed by the presence of hypertyrosinaemia, hypertyrosinuria and urinary excretion of phenolic acids, and the absence of hepato-renal lesion. Needle biopsy of the liver, which demonstrates the deficiency of soluble cytosolic tyrosine aminotransferase, is not indispensable to the diagnosis and was not performed in our patient. Treatment consisted of a dietary measure: a controlled phenylalanine and tyrosine intake to obtain a tyrosinaemia below 10 mg/100 ml. This resulted in a favourable and durable course of the oculo-cutaneous lesions. In case of isolated skin lesion, retinoids can be prescribed either alone of combined with a diet, making it less strict. PMID- 8363308 TI - [Palmoplantar linear porokeratocic hamartoma]. PMID- 8363309 TI - [Familial cutaneous amyloidosis]. AB - Familial diseases with skin lesions of amyloidosis are numerous and diverse, including widely different entities. The most homogeneous group is the one where cutaneous amyloidosis is clinically isolated and of the lichenoid type. It is probable that in most of these forms the amyloid protein is a keratin. A genetic approach of the candidate gene type would confirm or infirm this hypothesis. In the second group of diseases the lesions of amyloidosis are associated with other genodermatoses and with two other familial diseases: Partington's disease and hereditary multiple endocrine neoplasia with cutaneous and visceral lesions. The position of amyloidosis in these different diseases varies and the mechanisms of its occurrence are unknown. The third group is that of skin amyloidosis as part of hereditary systemic amyloidosis. Future advances in this matter will rest on the characterization of the amyloid protein involved and on the discovery of genetic abnormalities responsible for these diseases. PMID- 8363310 TI - [Physiopathology of scleroderma]. AB - Scleroderma (systemic sclerosis) is a connective tissue disease characterized by an excessive accumulation of collage in the main body organs. The subsequent progressive fibrosis may result in severe functional impairment of the tissue(s) involved. In this paper, recent advances in the understanding of the disease are reviewed. Particular emphasis is placed on the role played by vascular lesions, inflammatory cell infiltrates, autoimmunity and possibly abnormal secretion of cytokines in the disturbance of connective tissue production. A better knowledge of the pathophysiological process involved in scleroma might lead to the development of new therapeutic approaches. PMID- 8363311 TI - [A case for diagnosis: cutaneous alternariosis]. PMID- 8363312 TI - [Complications of local anesthetics]. PMID- 8363313 TI - [Drug-induced pseudolymphoma with predominantly cutaneous manifestation]. PMID- 8363314 TI - [Pruritus sine materia: a pharmacological approach]. PMID- 8363315 TI - [Effects of sublingual nifedipine on the velocity of pulse wave evaluated by Doppler echocardiography of the thoracic aorta]. AB - Sublingual nifedipine has a rapid and powerful hypotensive effect. Its action on arterial distensibility can be assessed by measurement of pulse wave velocity (PWV) by Doppler echocardiography (DE). Ten patients were used to evaluate intra observer reproducibility (Group 1). Fifteen hypertension patients (Group 2), not taking a calcium antagonist, 64 +/- 13 years-old, were studied by DE before and 15 minutes after 10 mg of SL nifedipine. The following were measured: systolic and diastolic blood pressures (SBP and DBP), heart rate (HR), echocardiographic shortening fraction (SF) and PWV, with sternal length (SL) taken as being identical to the length of the abdominal aorta between the isthmus and the coeliac region, and by measuring delta t: time interval for propagation of the pulsed Doppler velocimetric wave between the isthmic aorta and the coeliac aorta located by echocardiography: PWV = SL/delta t. Evidence was found in the nifedipine group (n = 15) of a fall in SBP (159.5 +/- 27.8 cf. 140.9 +/- 21 mmHg; p = 0.002); in DBP (88.6 +/- 13 cf. 79.6 +/- 8.3 mmHg; p = 0.005) and an increase in HR (72.3 +/- 10.7 cf. 76.8 +/- 12.9 bpm; p = 0.04). PWV decreased after nifedipine (10.5 +/- 3.9 cf. 7.15 +/- 12.9 bpm; p = 0.002). There was a linear correlation between the percentage reduction in PWV and left ventricular HR: y = 194x - 53; r = 0.56; p = 0.029.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363316 TI - [Symptomatic sinus dysfunction. A new use of electrophysiology]. AB - The authors undertook a prospective electrophysiological study of 950 patients: 53 subjects considered to be "controls" since they were free of any history of syncope or faintness were identified, as well as 39 symptomatic subjects with a strong suspicion of sinus dysfunction, since no other detectable cause of fainting episodes was found by extracardiac investigation, 24 hour ECG nor electrophysiology. Following the creation of a computerised tool enabling not only the entry of indirect tests, processing, averaging of results, printing and memorization, but also assistance in interpretation, several electrophysiological parameters were used: heart rate and existence of sinus arrhythmia, Strauss tests with adjusted data or not, effective nodal refractory period, Guize, Narula and Mandel tests, and an atropine (0.03 mg/kg) test which was performed only in the symptomatic group. These tests were studied by single-variate and correlative analysis to define their normal ranges, their critical values and their dependence or independence. The performance of each test (i.e. its efficiency, and the specificity and sensitivity of each critical value) was measured. Tests found to be most useful (specificity and efficiency > 90%) were as follows: Mandel test = CSRT > or = 534 ms, Narula test = TECASA > or = 339 ms, heart rate < or = 55/min, type II, IIa and chaotic Strauss curve associated with a pathological Guize test. The combination of these tests in this algorithm resulted in an increase in sensitivity to 84%, at the price of a very moderate fall in specificity to 87%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363317 TI - [Compression of the coronary trunk by aneurysm of the antero-left Valsalva sinus associated with acute mitral insufficiency caused by rupture of the chordae following valvular prolapse. Successful triple surgical operation in a 66-year old patient]. AB - Tearing of the chordae is a common complication of prolapse of the mitral valve; which becomes increasingly common with age. In contrast, aneurysm of the Valsalva sinus is rare in patients over 65 years of age. The antero-left sinus is an unusual location, but may be complicated by compression of the left coronary artery, which is reported in 16 cases in the literature. The case reported is unusual due to the combination in a 66-year old subject of acute mitral incompetence, due to tearing of the chordae following prolapse of the mitral valve, and an aneurysm pressing on the coronary trunk whilst remaining asymptomatic. Complete correction of the lesions was successfully achieved by surgery. PMID- 8363318 TI - [Left bundle-branch block and chest pain of simultaneous occurrence during exercise]. AB - The authors report a new case of left bundle branch block with pain during exercise, with arteriographically normal coronary arteries. Clinical findings and the course of the condition are reviewed. Pathophysiological mechanisms are discussed, with attribution of first place to an ischemic theory. PMID- 8363319 TI - [Value of the methylergometrin maleate test in recurrent cardio-circulatory arrests]. AB - A 56-year-old man, with no particular past history, sustained two cardio circulatory arrests preceded by constrictive chest pain. Coronary arteriography was normal during etiological investigations. The methylergometrine maleate (Methergin (tm)) test enabled the diagnosis of severe spastic angina and guided appropriate management of this patient. PMID- 8363320 TI - [Evaluation of embolic cerebrovascular complication: contribution of transesophageal echography]. AB - Ischemic cerebrovascular accidents are classically attributed to an embolism of cardiac origin in 15% of cases. This longstanding concept is questioned by trans esophageal echocardiography (TEE). The incidence of anomalies which could be the origin of a cerebral embolism involves more than 50% of cases in certain series. The superiority of TEE over trans-thoracic echocardiography (TTE) emerges in particular when certain abnormalities such as an intra-atrial thrombus, spontaneous atrial contrast, an intra-aortic atherosclerotic plaque, a patent foramen ovale or an aneurysm of the inter-atrial septum are sought. The high incidence of such abnormalities in a population having sustained an ischemic cerebrovascular accident is not sufficient to establish a cause-and-effect relationship between the abnormality and the cerebral event. Certain abnormalities are commonly associated with each other or with emboligenic arrhythmias (atrial fibrillation). Studies hence remain required to determine the respective responsibilities of these various abnormalities and stratify their embolic risk by defining certain risk factors. While awaiting the result of such studies, it would seem valid to suggest the more routine use of TEE in the investigation of ischemic cerebrovascular accidents in young patients free of clinically obvious heart disease, and this regardless of the result of TTE. PMID- 8363321 TI - [Triangular or rectangular rehabilitation after myocardial infarction. Comparative study by drawing of lots evaluating performance and respiratory gas exchange]. AB - Triangular and rectangular rehabilitation techniques were assessed by comparative exercise performance and respiratory evaluation in twenty six phase II post myocardial infarction patients. Patients all performed a standard exercise test with measurement of VO2, before and after 40 rehabilitation sessions. Clinical, exercise and ventilatory parameters were identical in the two groups before rehabilitation (triangular--n = 13; rectangular--n = 13). Exercise capacity was increased by 18% and 19% respectively after rehabilitation. Maximum aerobic capacity nevertheless remained unchanged (27.6 +/- 7.1 before; 28.3 +/- 6.7 ml/kg/min after) in all patients. Analysis of variance failed to reveal superiority of one of the two rehabilitation techniques over the other. PMID- 8363322 TI - [Infectious endocarditis on permanent endocavitary pacemakers: value of echocardiography and review of the literature]. AB - Infectious endocarditis around indwelling pacemakers is rare (0.15% of all implantations). They have a gloomy prognosis with a global mortality rate of nearly 34% as emerges from this review of the literature concerning 58 cases of infectious endocarditis published within the past 16 years. On the basis of the 6 cases which the authors report, they stress the importance and sometimes difficulty of using ultrasound in a positive diagnosis. Cardiographic ultrasound, which can determine the size and emboligenic nature of vegetations is capital in choosing how to remove the pacemakers. Percutaneous ablation by simply pulling or by catheterization currently gives the best results, but it may be necessary to resort to surgery involving right atriotomy if emboligenic vegetations are present. By combining antibiotic treatment and ablation of the intracavitary material, a cure is obtained in 92% of cases. These figures should be compared with the lack of success of using antibiotic treatment alone which results in a high level of mortality (84%). PMID- 8363323 TI - Quality of medical care and quality assurance. PMID- 8363324 TI - Quality assurance in medicine: research and evaluation activities towards quality control in Singapore. AB - Quality assurance and medical audit requires a good Health Management Information System (HMIS) to support it. In Singapore, there is a well developed HMIS built on the routine reporting of utilisation and activity statistics from public sector and private sector hospitals, government clinics and support services. In addition, there is a computerised national surveillance system for disease monitoring, which includes the disease condition, operations done and the physician and surgeon responsible for managing any inpatient or day case admitted into any hospital in Singapore. This forms the basis for the computerised national health system known as Medinet. Supplementing this are ad hoc surveys on quality of service, medical audit studies and supplementary information systems such as the Births and Deaths registration system and the Census of Population. Such a well developed HMIS greatly facilitates medical audit in Singapore. Indicators for audit can be generated from existing health databases, which point to areas requiring further inquiry and investigation. The use of a unique National Registration Identity Card (NRIC) for every Singaporean enables healthcare utilisation at all levels to be linked, further enhancing the capability for medical audit here. PMID- 8363326 TI - The unripe cervix and its management for labour induction. AB - Cervical state plays an important part in the outcome of induced labour. The mechanism governing the process of ripening, which is part of the continuum ending in labour, is still not fully understood, but is thought to involve several hormonal interactions including oestrogens, progesterone, and prostaglandins. The prostaglandins have been found to produce the best results for inducing labour when the cervix is unripe and are most effective when administered locally and most convenient when placed in the vagina as a viscous gel, wax pessary or slow release pessary. They are of benefit for labour induction in cases previously delivered by lower segment caesarean section, breech presentation, and multiple pregnancies. Hyperstimulation and fetal distress may occur and this might be reduced with the use of the controlled release hydrogel pessary. Newer approaches using an antiprogestin or recombinant relaxin are being explored in the hope that further improvements in outcome can be obtained. PMID- 8363325 TI - Trends in human immunodeficiency virus infection: epidemiology in Singapore. AB - The acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV) and recognised a decade ago, has reached pandemic proportions worldwide. By early 1992, the World Health Organisation estimates that at least 10 to 12 million people are infected with HIV globally. The majority of these infections are the result of heterosexual transmission. In South and South-east Asia, the AIDS pandemic is growing rapidly due to intravenous drug use and heterosexual transmission. Since 1985, the major route of HIV transmission in Singapore has been sexual. The transmission pattern, however, has changed from one that was predominantly homosexual or bisexual to one that is increasingly heterosexual from mid-1990. In addition, HIV infections among intravenous drug users, children and organ recipients who received transplantation overseas have also surfaced since 1990. It is estimated that there will be 400 cases of HIV infection in Singapore by the mid-1990s. PMID- 8363327 TI - Significance of assisted reproductive technology for other areas of medicine. AB - Assisted reproductive technology has achieved its place in the management of women with infertility. It is now being used to refocus gynaecological attention on patients with other enigmatic benign gynaecological conditions, such as endometriosis, and their medical treatments. Now that reasonable success rates can be achieved without risking unacceptable multiple pregnancy rates, many other medical disciplines are becoming involved. Specialists in these other disciplines need to modify their treatments accordingly to allow for future parenthood if this is appropriate. These specialists need also to be aware of past ethical dilemmas that infertility units have had to confront during the first ten years of this new technology. PMID- 8363328 TI - Occupational cancer in developing and newly industrialized countries. AB - Cancer is a worldwide public health problem, accounting for an increasing proportion of all deaths. It is the second leading cause of death in most of the industrialised world, and developing countries appear to be launched on a cancer epidemic, similar to that in industrialised countries. In developing countries, most cancer deaths are due to tumours of the stomach, oesophagus, lung, liver and uterine cervix; occupational cancers account for an undetermined number of these cases. Occupationally associated neoplasms may either be related directly to specific exposures within a workplace, e.g., bladder cancer in benzidine-exposed workers, or reflect indirect factors, including socioeconomic status and conditions of life. Asbestos-induced pneumoconiosis is recognised as an occupational disease in many developing countries, whereas asbestos-related malignancies draw less attention. The rising prevalence of cigarette smoking in these countries greatly magnifies the effect of asbestos in inducing lung cancer. Transplantation of industries from developed to developing countries is often accompanied by a reduction in the standard of working conditions. The rising unemployment in developing countries is unlikely to incite workers to claim better conditions. PMID- 8363329 TI - Changing prognosis of childhood cancer--an overview. AB - Significant advances in diagnosis and management have cured the majority of children with cancer. In the leukaemias, the commonest childhood malignancy, intensive induction-consolidation is important to ensure a lasting cure in about 65-80% and to eliminate the traditionally bad prognostic risk factors associated with less intensive treatment. Bone marrow transplantation (BMT) has a curative role in the minority who relapse particularly while on treatment. With few exceptions, most paediatric solid tumours are curable. Although the multimodal approach is responsible for the progress made, chemotherapy has emerged to play a dominant role. It has, in several tumours, obviated or reduced the need for radiotherapy and/or surgery. In Wilms' tumour and Hodgkin's disease, refinement of treatment is now in progress to reduce therapy-related morbidity while not sacrificing efficacy. PMID- 8363330 TI - Acute injury of the neck: anatomical and pathological basis of pain. AB - Headache, upper torso and upper limb pain can all originate in lesions of the cervical spine. The pain distribution is similar whether the cause is traumatic or degenerative. Nociceptive fibres are present in many cervical spine structures including the disc annulus, facet joint capsules, muscles, meninges, arteries, nerve roots and dorsal root ganglia. Such nerves are not present in the disc nucleus, facet articular cartilages and the ligamentum flavum. Central nervous connections between the trigeminal nucleus and upper cervical sensory input provide an explanation for some forms of headache and facial pain. This paper focuses on neck sprain from road traffic accidents as a cause of pain. Similar lesions are seen in the cervical spines of those who die immediately and survivors who die some years after a neck injury, from unrelated causes. Both discs and facet joints are injured. The common disc injury is a "rim lesion" or transverse tear near the anterior vertebral rim. It is caused by distraction and shearing in sudden extension. Both the posterior disc and the facets are compressed, causing disc contusion or herniation, facet haemarthroses, bruising around the C2 nerve, or fractures of articular processes. Suboccipital vascular congestion and annulus calcification are also seen in the "survivors". Chronic pain develops in 20-40% of the "survivors". The reasons include altered spinal mechanics, neural damage and vascular changes. Management must always start with an accurate diagnosis based on a history and physical examination. Simple investigations such as extension X-rays may reveal vacuum clefts in the same anatomical position as rim lesions. Nuclear scans detect increased uptake at damaged end plates or facet fractures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363331 TI - Facial pain: trigeminal neuralgia. AB - Atypical facial pain is a loose term used to encompass a wide range of facial pain syndromes including those of dental and ear, nose and throat (ENT) aetiology. Often, it is associated with psychiatric conditions like depression and psychosomatic illnesses. This facial pain typically does not follow anatomical boundaries or its explainable by present day neurophysiological understanding. The pain is often constant with no remission and is aggravated by stress. Treatment is difficult and often directed to the psychiatric cause. Surgical treatment is contraindicated. Trigeminal neuralgia on the other hand, can be effectively treated. Pain in the trigeminal distribution is paroxysmal, precipitated by trigger factors and there is no pain in between attacks. The aetiology of trigeminal neuralgia is still unknown though current thinking is that there is a peripheral disturbance or damage with cerebral brainstem disinhibition of the trigeminal apparatus. This results in a paroxysmal discharge and reverberation of pain impulses when a trigger point is elicited. Therefore, anti-epileptic drugs like tegretol can be effective in controlling trigeminal neuralgia in the majority of patients, at least in the initial stages. For unknown reasons however, medical treatment either is not effective at all from the very beginning or fails after a few years. Surgery then becomes the only available therapeutic option. If the peripheral disturbance is due to an organic cause like a tumour, surgical approaches should be directed towards its removal. Often the pain will also resolve. If the trigeminal neuralgia is of the idiopathic variety, then the surgeon has a choice of either peripheral percutaneous retrogasserian ganglionectomies or central approaches like microvascular decompression and trigeminal tractotomy. PMID- 8363332 TI - New directions in cardiovascular mapping and therapy. AB - Cardiovascular mapping has allowed us to fully understand the mechanisms of some of the cardiac arrhythmias and enabled us to devise new therapeutic options for them. Endocardial mapping by electrophysiological studies using three to four endocardial catheters introduced via the vein or artery to the heart allows us to directly map the electrical activity of the heart during sinus rhythm and during abnormal tachyarrhythmias. The simultaneous recording of electrical activity from the surface electrocardiogram, right ventricular apex, His bundle, high right atrium, coronary sinus, with or without a roving mapping catheter, enables us to precisely map the electrical activation sequence in the heart. This technique has been especially useful for mapping supraventricular tachycardias and the precise mapping of the accessory pathway or slow pathway potentials have now allowed us to selectively ablate them using radiofrequency energy delivered via the tip of the endocardial catheter. Intraoperative direct cardiac mapping has allowed us to reconfirm the findings of endocardial catheter mapping immediately prior to surgery. The intraoperative mapping is more precise and allows direct visualisation of the abnormal site for the surgeon to operate. Computerised mapping using multichannel recordings has facilitated mapping of the abnormal site for patients with haemodynamically unstable or nonsustained ventricular tachycardia, and thus allows the surgeon to perform surgical resection or cryoablation of the abnormal site. Cardiovascular mapping has thus enabled us not only to understand the mechanisms of cardiac arrhythmias but allows us to provide curative therapy for patients who are at risk from sudden arrhythmic death or otherwise need life long drug therapy. PMID- 8363333 TI - The 11th Gordon Arthur Ransome Oration: ethical and legal issues arising from new frontiers in medicine. PMID- 8363334 TI - Obstetric litigation--what are the problems. PMID- 8363335 TI - Quality assurance in medicine: a dental audit system. AB - Two principal components of a quality assurance system for dental plans are described, using a case report to illustrate the methodology. Criteria of acceptable quality of patient care for general practice were developed first. Then plan, practice and patient profiles, derived from claims or encounter data, were used to identify the nature and extent of aberrant patterns which were uncovered. Based on analysis of the profiles, site visits were made to a targeted sample of practices and selected patient dental records were evaluated for various levels of the process of care. Categories were rated as either acceptable or unacceptable. Principal dentists were debriefed on the findings and a report including corrective action plans prepared for the responsible agency. Follow-up to monitor compliance is planned. Although aberrant profiles do not necessarily mean that care is unacceptable, the findings from the record review confirmed the concerns raised by the data analysis. PMID- 8363336 TI - Quality assurance in the training of primary health care doctors and specialists. AB - Training of doctors is expensive as it requires at least six years of supervision while on the job plus sponsorship for courses, examination and even overseas training. Quality assurance of training is essential to ensure maximum throughput of the required number of specialist doctors for national needs. First, there is competition for training posts at basic (three years) and advanced (three years) levels. Basic training prepares doctors to sit and pass the relevant postgraduate examinations. Fifty percent of each cohort of doctors are selected as Basic Trainees but 40% finally complete Advanced Training. Second, trainees complete a training programme under supervision and record their clinical and learning experience in log books which are checked and certified by appointed supervisors who are consultants in government and restructured hospitals or institutions. Third, supervisor reports are submitted six monthly to the respective bodies: Academy of Medicine, School of Postgraduate Medical Studies or the Ministry of Health and Training Committees which vet these with the aim to continue the training or to terminate the training. Fourth, Parts I and II of relevant examinations must be passed within stipulated time frames. By these measures, there is quality assurance in the postgraduate training of our doctors. PMID- 8363337 TI - Neonatal jaundice: update on phototherapy management. AB - Phototherapy is now the standard form of treatment for infants with neonatal hyperbilirubinaemia. Though gradual in its effect, it finally produces a prolonged reduction in bilirubin values; retreatment with phototherapy is relatively rare. Factors that affect efficacy of phototherapy are: initial bilirubin level, birth weight, gestational age, postnatal age, aetiology of jaundice and light intensity and spectral emission. Phototherapy has now been demonstrated to be highly effective and safe; with simple precautions, no untoward side-effects will occur. The guidelines for commencement, monitoring and cessation of phototherapy are provided. PMID- 8363338 TI - Colonic pouch after low anterior resection of the distal third of the rectum. AB - Very low anterior resection with construction of colo-anal anastomosis for carcinoma of the distal third of the rectum may result in an increased bowel frequency and urgency. These latter problems have been correlated directly with the decreased capacity and compliance of the neo-rectum. Clinical trials have shown a significant advantage of the colonic pouch-anal anastomosis over conventional colo-anal anastomosis in decreasing post-operative bowel frequency and urgency as the former increases neo-rectal capacity. Recent innovations in pouch design and construction with the ingenious use of mechanical stapling devices will enable the widespread use of the colonic pouch to benefit more patients who require very low anterior resection for carcinoma of the distal third of the rectum. PMID- 8363339 TI - The modified radical mastectomy of Patey: technique and experience. AB - We report our experience from 193 patients with breast cancer treated by Modified Radical Mastectomy of Patey and describe the technique used, amplified by illustrations. We achieved a low morbidity viz symptomatic lymphoedema five cases, chronic shoulder stiffness one case, skin grafting two cases, and all cases of chest wall pain cleared by four years. Cancer recurred, to date, local in nine cases (4.6%), local and systemic in 17 cases (8.9%) and systemic in 27 cases (13.9%). We compile, for the first time, all references by Patey and Richard Handley to the procedure. We recommend the operation as achieving complete primary clearance with safe and full axillary node removal. Histological state of the nodes allows rational decisions on adjuvant therapy with hormones and chemotherapy. PMID- 8363340 TI - Poisons information in Singapore. AB - The Poisons Information Centre (PIC) provides viral and timely information to prevent and manage poisoning episodes. Comprehensive information on household, agricultural and industrial chemicals, natural toxins, pharmaceuticals, local antidote stocks and local poisons experts is retrieved from the Centre's computerised information system and printed literature. Public subscribers can obtain poisons information through Teleview. PMID- 8363342 TI - Multifocal mucus secreting papillary adenocarcinoma of the bile duct causing obstructive jaundice. AB - We present a 64-year-old Malay lady who had undergone a choledochoduodenostomy (CDD) two years ago for obstructive jaundice. She was admitted with jaundice and underwent ultrasonography, percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangio pancreatography (ERCP) and computed tomographic (CT) scanning of the liver and biliary tree. All the investigations confirmed a type IVa choledochal cyst. At operation, the grossly dilated biliary system was packed with a thick mucoid material and the mucosa of the bile ducts was visibly abnormal with scattered nodules. This mucoid material had caused occlusion of the entire biliary tree resulting in obstructive jaundice. To the best of our knowledge, this is probably the first report of obstructive jaundice caused by thick mucus. The peculiar management problems of this case and the risk of malignant change in choledochal cysts are discussed. PMID- 8363341 TI - Altered immunity in haemophiliacs treated exclusively with cryoprecipitate. AB - Sixty-five patients with haemophilia A from Singapore General Hospital, treated within the last 15 years exclusively with cryoprecipitate, were studied for the effect of the total number of exposures to random blood donors on their immune system. These haemophiliacs were aged 4 to 71 years (median 24 years) and were all apparently healthy with no clinical evidence of viral infection. None of them was a homosexual or intravenous drug user. All of them tested negative for human immuno-deficiency virus antibody and hepatitis B surface antigen. Analysis of the T-lymphocyte subset population showed 20 out of 65 haemophiliacs or 30.8% had reversal of T4/T8 ratio, ie. less than 1.00. There was no significant difference in the mean age of the 20 patients with abnormal T4/T8 ratios compared with the 45 with normal T4/T8 ratios. The mean age of the former group was 23 and the latter was 25. The group with reversal of T4/T8 ratio had exposure to 827.4 +/- 137.3 (mean +/- SEM) random blood donors, which is significantly higher than 402.5 +/- 64.1 in the group with normal T4/T8 ratio (p < 0.05). The reversal of T4/T8 ratio is predominantly due to the suppression of absolute T4 cell counts, with slightly raised absolute T8 cell counts. This abnormality may be transient or permanent. Interestingly, all the six out of 65 haemophiliacs with factor VIII inhibitor did not show any reversal of T4/T8 ratio in this study. PMID- 8363343 TI - Clinical profile of stage D carcinoma of the prostate--a ten-year experience. AB - Carcinoma of the prostate has become one of the top ten malignancies in Singapore but to date, there has been little local clinical data available on the disease. This study aims to establish the clinical profile of Stage D carcinoma of the prostate in the local population. Forty-seven patients with Stage D disease treated by the department over a ten-year period, 1981-90, were studied. The majority (47.7%) fell in the age-group 66-75 years and the most common presenting symptom was bone pain (36.2%). Both acid and alkaline phosphatases were found to be poor diagnostic markers of the extent of the disease. Acid phosphatase was not elevated in 25.0% and alkaline phosphatase not elevated in 39.1% of our patients. Forty of these patients had orchidectomy and of these, ten were also treated with oral stilbesterol. Five-year survival for the orchidectomy group was 22.7% and that for the orchidectomy-plus-stilbesterol group was 23.0%. This compares well with other studies done in the West. Eight patients died within the first year of diagnosis but of those who survived, all remained symptom-free within this first year. The proportion of those who remained symptom-free fell to 25.0% of the survivors for subsequent years. PMID- 8363344 TI - Hepatic candidiasis: persistent pyrexia in a patient with acute myeloid leukaemia after recovery from consolidation therapy-induced neutropenia. AB - Fever, a frequent manifestation in acute leukaemia patients who develop treatment induced neutropenia, usually resolves when the neutrophil count returns to normal irrespective of whether an infective agent is isolated or not. A persistent pyrexia following neutrophil recovery and associated with multiple negative microbiological cultures should signal a careful search for a deep-seated fungal infection in any leukaemic patient who is complete remission. We report here a 39 year-old Chinese man with acute myeloid leukaemia in first complete remission whose unresolved fever after recovery from consolidation therapy-induced neutropenia was ultimately confirmed to be caused by focal hepatic candidal microabscesses by an open liver biopsy. PMID- 8363345 TI - Third chapter of surgeons lecture: revolution in urology and its evolution in Singapore. AB - Urology has been an evolving specialty since the time of Hippocrates. The itinerant surgeon was known to go from town to town to remove bladder stones in the early middle ages. In this century, urologists had been at the forefront in pioneering minimally invasive surgery with the introduction of transurethral resection of the prostate more than 50 years ago in the United States. This could be considered the first revolution in urology and this has influenced the evolution of urology in Singapore. Transurethral surgery had proved to be far superior to open surgery for most lesions of the lower urinary tract. This technique was introduced to Singapore in the early 1970s by Dr N E Wong. Because of the need for special instruments, skill and training, there was a need for a Department of Urology. This was not to be until after the second revolution in urology. The second revolution saw the introduction of endoscopic surgery of the upper urinary tract and Extra-corporeal Shockwave Lithotripsy in the early 1980s. This had truly revolutionised the treatment of urinary stones and today almost 95% of patients can be treated with these non to minimally invasive techniques. These new modalities of treatment were rapidly introduced in Singapore in the mid 1980s. The need for the establishment of urology as a specialty was more urgently felt. The Singapore Urological Association was formed in February 1986 and in March 1987, a Division of Urology was formed at the Singapore General Hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363346 TI - Distinguished academician 1992 lecture. Role of the surgeon in scientific medical progress. PMID- 8363347 TI - Synaptic plasticity in Alzheimer's disease. PMID- 8363348 TI - Transplants for stroke patients? PMID- 8363349 TI - Human positron emission tomographic [18F]fluorodopa studies correlate with dopamine cell counts and levels. AB - Postmortem counts of dopaminergic cell densities in the substantia nigra (5 subjects) and striatal levels of dopamine (DA) and its metabolites (6 subjects) were determined on 1 parkinsonian (PD), 3 progressive supranuclear palsy (PSP), 1 amyotrophic lateral sclerosis, and 1 Alzheimer's case who had been positron emission tomography scanned with 6-[18F]fluorodopa during life. [18F]Fluorodopa uptake rate constants, which presumably depend on the number of functioning striatal DA terminals, were strictly proportional to cell densities (significant correlation with zero intercept) and also correlated significantly with striatal DA levels but with an intercept indicating greater losses of DA than of terminals in PSP and PD. Postmortem data on 6 PD, 1 PSP, and 9 neuronally normal controls substantiated the significant correlation between cell counts and DA levels, with the latter being the more depressed in pathological cases. PMID- 8363350 TI - Correlation of striatal fluorodopa uptake in the MPTP monkey with dopaminergic indices. AB - Striatal 18F-6-fluorodopa (FD) uptake constants were measured by positron emission tomography in (1) normal cynomolgus monkeys and (2) a series of cynomolgus and rhesus monkeys that had received intracarotid infusions of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After the animals were killed, the number and average size of dopaminergic neurons in the substantia nigra pars compacta were measured. Striatal levels of dopamine and its metabolites, and the striatal activities of the dopaminergic synthetic enzymes, were also determined. The striatal FD uptake constants showed highly significant positive correlations with both number and size of dopaminergic neurons, indicating atrophy of surviving neurons in MPTP-treated animals. The uptake constants also showed significant positive correlations with striatal levels of dopamine, total catecholamines, and the activities of the synthetic enzymes. Both histochemical and biochemical data on tyrosine hydroxylase suggested some contralateral enzyme loss in these MPTP-treated monkeys, as well as decreased enzyme activity in surviving neurons on the lesioned side. However, residual enzyme activities were apparently not rate limiting to striatal FD uptake. It is concluded that PET-FD measurements by positron emission tomography provide a good index of the integrity of the nigrostriatal pathway. PMID- 8363351 TI - Magnetic stimulation of the brain in generalized epilepsy: reversal of cortical hyperexcitability by anticonvulsants. AB - Observations on experimental models suggest that diffuse cortical hyperexcitability is an important abnormality in the generalized epilepsies. We used the threshold for transcranial magnetic stimulation as an index of motor cortical excitability in 89 neurologically normal control subjects and 56 patients with idiopathic generalized epilepsy (20 untreated and 36 chronically treated with anticonvulsants). Magnetic stimulation was repeated in 10 patients after valproate monotherapy had been commenced and in 23 control subjects. The threshold intensity was significantly lower in the untreated patients (46 +/- 5% [mean +/- 95% confidence interval]) than in the control subjects (56 +/- 2%). Treated patients had significantly higher thresholds (64 +/- 4%) than did untreated patients and control subjects. A significant increase in threshold intensity (8 +/- 2%) occurred in patients retested after starting valproate; there was no significant change in retested control subjects (-1 +/- 2%). Threshold intensity was positively correlated with plasma valproate levels (rs = 0.37). The findings suggest that cortical excitability is increased in idiopathic generalized epilepsy and is reduced following anticonvulsant treatment. Transcranial magnetic stimulation is of use in examining the pathophysiology of generalized epilepsy. Furthermore, changes in threshold intensity in response to anticonvulsant treatment may prove useful in guiding therapy. PMID- 8363352 TI - Quantitative assessment of synaptic density in the entorhinal cortex in Alzheimer's disease. AB - We quantified the synaptic density in the entorhinal cortex (Brodmann area 28) in autopsy material from 10 individuals with Alzheimer's disease and compared them to 11 age-matched, postmortem-matched control subjects without dementia, using standard electron microscopy. The statistical data showed no change in synaptic density between control and Alzheimer subjects, in either lamina III or V of the cortex. There were no correlations between synaptic density and synaptic apposition length or density of senile plaques. The entorhinal cortex stands in marked contrast to other cortical areas that show a significant decline in synaptic numbers with Alzheimer's disease. This preservation of synaptic numbers may be related to a plasticity response that is greater in the entorhinal area than in other areas of the cortex. PMID- 8363353 TI - Functional integration of cortical grafts placed in brain infarcts of rats. AB - Five to 6 days after a right middle cerebral artery occlusion, a cell suspension of fetal neocortex was grafted into the infarcted area of adult spontaneously hypertensive rats. Three to 17 months later, functional integration of the grafts into the afferent somatosensory pathway was tested using the 2-[14C]deoxyglucose method for estimation of glucose utilization. Grafted rats (n = 8) and control rats (n = 5) with no arterial occlusion were stimulated in the left vibrissal region resulting in an increased glucose utilization in the left trigeminal sensory nucleus and the right ventroposterior nucleus of the thalamus, whereas the same regions in a group (n = 5) of nonstimulated grafted rats were not activated. Glucose uptake in the right somatosensory cortex of control rats was 96 +/- 5 (mean +/- SEM) mumol/100 gm/min. Neocortical grafts consumed less glucose than cortex in control rats but the vibrissae-stimulated group displayed a 110% higher value than the nonstimulated grafted group (32 +/- 5 vs 15 +/- 2, p < 0.05). We conclude that graft glucose metabolism is increased following stimulation of the host somatosensory pathway, which demonstrates that transplanted neurons can be functionally integrated with neural circuitries of the host after an ischemic insult. PMID- 8363354 TI - Differential neural activity in the human temporal lobe evoked by faces of family members and friends. AB - In 6 patients, depth electrodes revealed differential evoked responses to familiar versus novel faces. These differential responses were obtained in the amygdala, hippocampus, and temporal neocortex but not in the dorsolateral frontal or cingulate cortex. The limbic and temporal structures that differentiated novel from familiar faces did not respond differentially to variations in luminance. Limbic structures and temporal cortex thus appear to participate in face recognition and in encoding the familiarity of visual experiences. PMID- 8363355 TI - Neurological cholinesterases in the normal brain and in Alzheimer's disease: relationship to plaques, tangles, and patterns of selective vulnerability. AB - Butyrylcholinesterase (BChE) and an altered form of acetylcholinesterase (AChE) accumulate in the plaques and tangles of Alzheimer's disease (AD). The sources for these plaque- and tangle-bound cholinesterases have not been identified. We now report that AChE and BChE activities with pH preferences and inhibitor selectivities identical to those of plaque- and tangle-bound cholinesterases are found in the astrocytes and oligodendrocytes of control and AD brains. These glial-type cholinesterases are selectively inhibited by indolamines and protease inhibitors. In control brains glial-type cholinesterases appear confined to the intracellular space, whereas in patients with AD they decorate plaques and tangles as well. In control and AD brains AChE-positive glia are distributed throughout the cortical layers and subcortical white matter, whereas BChE positive glia reach high densities only in the deep cortical layers and white matter. In non-AD control brains, the ratio of BChE to AChE glia was higher in entorhinal and inferotemporal cortex, two regions with a high susceptibility to the pathology of AD, than in primary somatosensory and visual cortex, two areas with a relatively lower susceptibility to the disease process. There was no age related differences in the density or distribution of cholinesterase-positive glia. In comparison with age-matched control specimens, AD brains had a significantly higher density of BChE glia and a lower density of AChE glia in entorhinal and inferotemporal regions but not in the primary somatosensory or visual areas. These results suggest that glia constitute a likely source for the cholinesterase activity of plaques and tangles and that a high ratio of BChE- to AChE-positive glia may play a permissive or causative role in the neuropathology of AD. PMID- 8363356 TI - Conjugal Alzheimer's disease: is there an increased risk in offspring? AB - Thirty-one couples in which both spouses had the clinical diagnosis of Alzheimer's disease (AD) (confirmed by autopsy in 12) were ascertained. The mean age of onset of dementia was 75.1 +/- 7.4 years. These couples had 87 children, 63 still living. Seventeen (19.5%) of the children developed dementia, with a mean age of onset of 68.9 +/- 8.3 years. Thirty of the children of the conjugal AD couples survived to age 65 or longer and 14 (47%) of them developed dementia. This prevalence of dementia in the children of affected couples is much greater than that in the children of two control groups consisting of 234 couples in which one spouse had AD and 192 couples in which neither spouse was demented. Twenty-one of the conjugal AD couples had a family history of AD but the prevalence of dementia in their children was not greater than that in the children of conjugal AD couples without a family history of AD. These results represent additional evidence of an important genetic component in late-onset AD and provide empirical risk data for the children of conjugal AD couples. PMID- 8363357 TI - Cortical vascular abnormalities in the syndrome of celiac disease, epilepsy, bilateral occipital calcifications, and folate deficiency. AB - The pathological changes in the syndrome of celiac disease, folate deficiency, bilateral occipital calcifications, and intractable epilepsy have not been previously described. A child with this disorder had a field defect correlating with active lateralized epileptic discharges and asymmetrical lesions. After resection of the right occipital lobe she was seizure free for 4 years. A cortical vascular abnormality with patchy pial angiomatosis, fibrosed veins, and large jagged microcalcifications was found. These pathological abnormalities were similar though not identical to those found in the Sturge-Weber syndrome. PMID- 8363358 TI - Role of the left and right supplementary motor areas in memory-guided saccade sequences. AB - Six right-handed patients with a lesion affecting the left (3 patients) or right (3 patients) supplementary motor area were studied using single and sequential memory-guided saccade paradigms. Accuracy of single saccades was preserved in both groups, compared to control subjects, and the chronology of saccade sequences was disturbed in the group with the left lesion but not in the group with the right lesion. The results suggest that neither side of the supplementary motor area is involved in spatial memory, and that the left supplementary motor area plays a greater role in motor sequencing than does the right supplementary motor area. PMID- 8363360 TI - Pain-triggered seizures. PMID- 8363359 TI - Failure of 3,4-diaminopyridine to reverse conduction block in inflammatory demyelinating neuropathies. AB - 3,4-Diaminopyridine was administered to 6 patients with inflammatory demyelinating neuropathies in whom partial conduction block was demonstrable. Four had Guillain-Barre syndrome and 2 had chronic inflammatory demyelinating neuropathy. Nerve conduction studies were performed before the administration of a single oral dose of 3,4-diaminopyridine, and at regular intervals thereafter. Neither resolution of conduction block nor clinical benefit were seen. PMID- 8363361 TI - Laser microprobe mass analysis in Alzheimer's disease. PMID- 8363362 TI - Aphasic dementia and motor neuron disease. PMID- 8363363 TI - Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson's disease. AB - Parkinson's Disease (PD) is characterized by a selective loss of nigrostriatal dopaminergic neurons that results in a marked reduction of dopaminergic nerve terminals in the striatum. Recently, 11C-WIN 35,428, a cocaine analogue that specifically labels the dopamine transporter, was developed and can be used to label dopaminergic nerve terminals in vivo by positron emission tomography. In healthy control subjects, binding of 11C-WIN 35,428 is highest in the striatum. In addition, 2 symmetrical focal areas of low binding were observed in the midbrain. The cerebellum functioned as an appropriate region for nonspecific binding. The binding of 11C-WIN 35,428 in patients with PD (Hoehn-Yahr II) was compared with that in healthy control subjects by using the (region cerebellum)/cerebellum ratio for data acquired 34 to 82 minutes after injection. In control subjects, this ratio varied, at approximately 2, in the striatum. In patients with PD, binding in the posterior putamen was reduced by 78%, whereas the anterior putamen and the caudate nucleus showed a reduction of 59 and 39%, respectively. The reduction in 11C-WIN 35,428 binding was highest in the midbrain (84%). The high specific/nonspecific binding ratio and the pronounced reduction in binding in mild PD may permit detection of even earlier stages of PD or presymptomatic individuals with dopaminergic cell loss. PMID- 8363364 TI - Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples. PMID- 8363365 TI - Characterization of the gene for chromosomal trimethoprim-sensitive dihydrofolate reductase of Staphylococcus aureus ATCC 25923. AB - The gene for the trimethoprim-sensitive (Tmps) chromosomal dihydrofolate reductase (DHFR) of Staphylococcus aureus ATCC 25923 was cloned and characterized. The structural gene encodes a polypeptide of 159 amino acid residues and has a calculated molecular weight of 18,251. The amino acid sequences of this Tmps DHFR and those of the trimethoprim-resistant type S1 DHFR encoded by transposon Tn4003 are 80% identical. In contrast to the trimethoprim resistant enzyme, the Tmps DHFR can be highly overexpressed in Escherichia coli, with most of the recombinant protein occurring in a soluble and an active form. PMID- 8363366 TI - Penicillin-binding proteins of Rhodococcus equi: potential role in resistance to imipenem. AB - Rhodococcus equi is a gram-positive coccobacillus which, like other members of the order Actinomycetales, is increasingly reported as an opportunistic pathogen in patients with AIDS. The use of combinations of antibiotics that include imipenem (IMP) has been suggested for the treatment of patients infected with R. equi. An antagonism between IMP, meropenem, cefoxitin, ceftriaxone, moxalactam, and oxacillin and other beta-lactams, such as penicillin, amoxicillin, cephalothin, and ticarcillin, was detected in vitro both on Mueller-Hinton agar and in broth for all 10 IMP-susceptible R. equi strains examined. To study the mechanism of the antagonism between beta-lactams, a mutant with decreased susceptibility to IMP (isolate IpR) was selected in vitro from a susceptible clinical isolate of R. equi (isolate IpS). IpR exhibited decreased susceptibility to IMP, meropenem, cefoxitin, ceftriaxone, moxalactam, and oxacillin but not to penicillin, amoxicillin, cephalothin, or ticarcillin. No beta-lactamase was found in IpS, IpS cultured with antagonistic beta-lactams, or IpR strains. Labeling of penicillin-binding proteins (PBPs) revealed four PBPs with molecular masses of ca. 59, 56, 43, and 26 kDa in IpS. In IpR, PBP 3 disappeared and was replaced by PBP 3a of 40 kDa. The 50% saturation of PBP 3 and PBP 3a by the carbapenems correlated with the MICs of these antibiotics, respectively, for IpS and IpR strains. However, PBP 3a was not detected in IpS when IpS was cultured in the presence of beta-lactams, with which antagonism was observed. The present work describes the PBPs of R. equi and reports that IMP resistance in R. equi is related to an altered PBP pattern. PMID- 8363367 TI - Antibiotic susceptibilities of Afipia felis in axenic medium and in cells. AB - Afipia felis, one of the putative agents of cat scratch disease (CSD), is a facultative intracellular bacterium. Although CSD is considered not to be susceptible to antibiotic therapy, sporadic case reports indicated that aminoglycosides may be effective. We determined the in vitro antibiotic susceptibilities of three A. felis strains in axenic medium and in a cell model. In axenic medium, A. felis was susceptible to imipenem, aminoglycosides, and rifampin when using either the broth dilution technique or the agar technique. When grown in HeLa cells, A. felis was susceptible to amikacin and tobramycin but was resistant to the other compounds tested. Despite its intracellular location, A. felis can apparently be reached by aminoglycosides. Thus, the in vitro data presented here are in accord with the clinical data obtained in patients suffering CSD. PMID- 8363368 TI - Pharmacokinetics of cefepime in cystic fibrosis patients. AB - The purposes of this study were to determine and compare the single- and multiple dose pharmacokinetics of cefepime in patients with and without cystic fibrosis. Twelve patients with cystic fibrosis hospitalized for treatment of acute pulmonary exacerbations were studied. In addition, pharmacokinetic data for seven of the patients with cystic fibrosis were compared with those for seven age matched control patients. The cefepime dose was 50 mg/kg of body weight (maximum, 2 g) administered as a 30-min intravenous infusion every 8 h for a minimum of 8 days. Serial plasma and urine samples, obtained after the first and last doses, were analyzed for cefepime content by a validated high-pressure liquid chromatographic assay. By standard noncompartmental analysis, the pharmacokinetic parameters ascertained were area under the concentration in plasma-time curve, elimination half-life, total body clearance, renal clearance, and volume of distribution at steady state. In addition, the maximum concentration in plasma was recorded. Mean (+/- standard deviation) results of the first dose analysis in patients with cystic fibrosis were as follows: maximum concentration in plasma, 142.6 (+/- 26.07) micrograms/ml; area under the concentration in plasma-time curve, 265.3 (+/- 114.31) micrograms.h/ml; elimination half-life, 1.8 (+/- 0.53) h; total body clearance, 127.2 (+/- 50.94) ml/min; renal clearance, 91.1 (+/- 38.86) ml/min/kg; volume of distribution at steady state, 14.1 (+/- 4.31) liters. Analysis for the last dose in patients with cystic fibrosis did not vary appreciably from these values, nor did those from the controls. Thus, it appears that the first-dose pharmacokinetics of cefepime are predictive of those at steady state. In order to consistently exceed the MIC for Pseudomonas aeruginosa for the entire dosing interval in patients with cystic fibrosis, a higher dose and/or different dosing interval compared with those used in this study may be necessary. PMID- 8363370 TI - Pharmacokinetic interaction between rifampin and zidovudine. AB - A potential pharmacokinetic interaction between rifampin (Rimactan, Rifadin) and zidovudine (AZT, Retrovir) was investigated in the population of human immunodeficiency virus-infected patients at our hospital. The results from four patients who were on long-term (> or = 6 months) combination therapy with zidovudine and rifampin are presented. In all cases of combined use of zidovudine and rifampin, a lower area under the plasma concentration-time curve (AUC) and, consequently, a higher apparent clearance of zidovudine were found, compared with a reference population of zidovudine users. Patients had a low to normal maximum concentration of zidovudine in plasma. Elimination half-lives were normal in all but one patient. Zidovudine glucuronide concentrations were determined in three patients and three control subjects. The patients all had relatively higher peak plasma concentrations and higher AUCs of zidovudine glucuronide than the control subjects. In one patient, zidovudine and zidovudine glucuronide were also measured 2.5 months after discontinuation of rifampin. The AUC of zidovudine increased by a factor of 2. These data are in agreement with an enzyme-inducing effect of rifampin on the glucuronidation of zidovudine. They indicate that long term combination therapy of rifampin and zidovudine leads to increased clearance of zidovudine, which may have therapeutic consequences. PMID- 8363369 TI - Anti-Pneumocystis carinii activity of PS-15, a new biguanide folate antagonist. AB - A newly synthesized biguanide inhibitor of dihydrofolate reductase in Plasmodium species was evaluated for its anti-Pneumocystis carinii activity. The compound N 3-(2,4,5-trichlorophenoxypropyloxy)-N'-(1-methylethyl)imidoca rbonimidic diamide hydrochloride, designated PS-15, was administered prophylactically and therapeutically to immunosuppressed rats latently infected with P. carinii. Doses of 5 and 25 mg of PS-15 per kg of body weight per day given orally during 7 weeks of dexamethasone immunosuppression prevented P. carinii infection in all (100%) 19 rats given the drug, while 6 of 9 (67%) untreated control rats developed P. carinii pneumonitis. A single weekly dose of 50 mg of PS-15 per kg also prevented the infection in all 10 rats. P. carinii pneumonitis was established after 4 weeks of immunosuppression and was then treated orally for 3 weeks with 25, 5, and 1 mg of PS-15 per kg/day. Complete resolution of the infection occurred in all (100%) 10 rats given 25 mg of PS-15, 6 of 9 (67%) rats given 5 mg of PS-15, and 6 of 8 (75%) rats given 1.0 mg of PS-15 per kg per day and in all (100%) 9 rats treated with trimethoprim-sulfamethoxazole. PS-15 was well tolerated at all doses. Because drug studies in the P. carinii rat model have been highly predictable of the effects of drugs on the disease in humans, these experiments suggest that PS-15 may have promise as a drug for the treatment of P. carinii pneumonitis in humans. PMID- 8363371 TI - Shedding of Clostridium difficile, fecal beta-lactamase activity, and gastrointestinal symptoms in 51 volunteers treated with oral cefixime. AB - Microbial changes including the shedding of Clostridium difficile, fecal beta lactamase activity, and gastrointestinal symptoms were assessed in 51 healthy volunteers given 200 mg of cefixime twice daily for 8 days. The number of organisms of the family Enterobacteriaceae (means +/- standard deviations) dropped from 6.9 +/- 1.1 to 3.9 +/- 1.8 log CFU/g of feces (P < 0.01), whereas counts of enterococci rose from 7.0 +/- 1.5 to 9.0 +/- 1.0 log CFU/g of feces (P < 0.01). Both counts returned to their initial levels 50 days after the cessation of treatment. Cefixime did not significantly modify the frequency of fecal excretion of Pseudomonas aeruginosa, Staphylococcus spp., yeasts, or members of the Enterobacteriaceae resistant to ceftazidime or ampicillin. The proportion of subjects shedding C. difficile rose from 6% before treatment to 57% (P < 0.01) at the end of treatment but returned to 8% 50 days thereafter. No case of pseudomembranous colitis was observed. Stool changes occurred in 13 volunteers during treatment (25%) and in 2 others more than 10 days after the end of treatment (4%). These changes were not significantly associated with the shedding of toxigenic strains of C. difficile or with the presence of toxin A in feces. By contrast, during treatment, stool changes occurred in 8 of the 18 volunteers (44%) who had antibiotic activity in their feces but in only 5 of the 33 (15%) for whom no such activity was found (P < 0.05). The absence of antibiotic activity in the feces was itself linked with the presence of beta-lactamase activity in the feces. Since we had found earlier that fecal beta-lactamase activity afforded protection against alteration in stool consistency during treatments with oral cephalosporins, the present study confirmed our previous preliminary results in this respect. PMID- 8363372 TI - Synergistic combinations of Ro 11-8958 and other dihydrofolate reductase inhibitors with sulfamethoxazole and dapsone for therapy of experimental pneumocystosis. AB - We compared Ro 11-8958, an analog of trimethoprim (TMP) with improved antimicrobial and pharmacokinetic properties, other dihydrofolate reductase (DHFR) inhibitors, sulfamethoxazole (SMX), and dapsone (DAP) in the treatment of Pneumocystis carinii pneumonia in an immunosuppressed rat model. In contrast to previous reports, high dosages of the DHFR inhibitors were used in combination with fixed, low dosages of SMX (3 mg/kg of body weight per day) or DAP (25 mg/kg/day). When administered alone at these dosages, SMX and DAP reduced the median P. carinii cyst count about 5- to 15-fold. Ro 11-8958, TMP, and diaveridine used at a dosage of 20 mg/kg/day with SMX were only slightly more effective than SMX used alone. However, administration of these DHFR inhibitors at a dosage of 100 mg/kg/day with SMX lowered the cyst count about 500- to 1,000 fold, indicating a synergistic effect. Little or no synergism was found when other DHFR inhibitors (pyrimethamine, cycloguanil, and tetroxoprim) were combined with SMX. Regimens of Ro 11-8958 at a dosage of 20 mg/kg/day with DAP and of TMP or diaveridine used at a dosage of 100 mg/kg/day with DAP showed comparable anti P. carinii activity, lowering the cyst count 100- to 200-fold. By contrast, Ro 11 8958 administered at a dosage of 100 mg/kg/day with DAP reduced the cyst count > 1,000-fold. Thus, the experimental approach used here enables the rat model of pneumocystosis to be used to compare synergistic combinations of antifolate drugs. The favorable results achieved with Ro 11-8958 indicate that it should be considered for clinical trials. PMID- 8363373 TI - In vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents. AB - The in vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents was investigated. The antimicrobial agents evaluated included ceftizoxime, FK037, cefotaxime, dirithromycin, clarithromycin and its metabolite 14-hydroxy clarithromycin, erythromycin, doxycycline, amoxicillin, ciprofloxacin, and ofloxacin. Isolates of B. burgdorferi tested included two reference strains (B31 and ATCC 53899), six isolates from the midwestern United States, and three from Europe. A broth macrodilution method was used to determine MICs and MBCs. B. burgdorferi was inhibited by < or = 0.5 micrograms of each of the agents except the quinolones per ml. The MBCs for 90% of strains tested of ceftizoxime, FK037, clarithromycin, 14-OH clarithromycin, and dirithromycin (< or = 1.0 microgram of each per ml) were superior to those of amoxicillin (2.0 micrograms/ml) and doxycycline (4.0 micrograms/ml). Further in vivo studies are warranted to determine whether these agents may be efficacious in the treatment of Lyme borreliosis. PMID- 8363374 TI - Comparison of ampicillin-sulbactam with vancomycin for treatment of experimental endocarditis due to a beta-lactamase-producing, highly gentamicin-resistant isolate of Enterococcus faecalis. AB - Increasing antibiotic resistance in the enterococci, including the capacity for beta-lactamase production and the development of high-level aminoglycoside resistance, has complicated the treatment of serious enterococcal infections, which often require synergistic antibiotic combinations for cure. We utilized the rabbit model of aortic valve endocarditis to investigate the effects of various antibiotics, alone and in combination, against a multiply antibiotic-resistant isolate of Enterococcus faecalis. Female New Zealand White rabbits were infected with either a beta-lactamase-producing, gentamicin-resistant isolate of E. faecalis or a non-beta-lactamase-producing, aminoglycoside-susceptible isolate, and the mean log10 CFU per gram of vegetation were determined. The most active agents were low-dose ampicillin-sulbactam (200 mg/kg of body weight per day), high-dose ampicillin-sulbactam (400 mg/kg of body weight per day), and vancomycin (150 mg/kg of body weight per day), which reduced the titers of bacteria by 2.27, 2.76, and 2.85 log10 (CFU/g, respectively, compared with controls. While ampicillin-sulbactam and vancomycin were equally efficacious in reducing titers of bacteria in vegetations, no animals were cured (defined as < 2 log10 CFU/g of vegetation) by either agent, whether treatment was continued for 3 or 7 days. The addition of gentamicin was not associated with increased killing in rabbits infected with the aminoglycoside-resistant isolate. Both high-dose ampicillin sulbactam and vancomycin regimens demonstrated significant, continued reduction in bacterial titers with the longer periods of treatment (P < or = 0.05); 7-day treatment with high-dose ampicillin-sulbactam produced a greater reduction in bacterial titers in vegetation than 7-day treatment with vancomycin (P < or = 0.05). We conclude that ampicillin-sulbactam and vancomycin are equally effective in the treatment of experimental endocarditis due to beta-lactamase-producing, highly gentamicin-resistant E. faecalis. The optimum therapy for such infections in humans is not known. PMID- 8363375 TI - Evaluation of bacterial interference and beta-lactamase production in management of experimental infection with group A beta-hemolytic streptococci. AB - The in vivo effects of penicillin and cefprozil therapy on the interaction between organisms commonly recovered from inflamed tonsils were studied by using a subcutaneous abscess model in mice. These organisms were group A beta-hemolytic streptococci (GABHS), Streptococcus salivarius (which is capable of interfering with GABHS), and Staphylococcus aureus. In mice infected with GABHS and S. salivarius alone or in combination, penicillin eliminated both organisms and cefprozil eliminated GABHS and S. aureus but not S. salivarius. Penicillin did not, however, reduce the number of GABHS or S. salivarius in the presence of S. aureus. The present study demonstrated the ability of beta-lactamase-producing S. aureus to protect GABHS from penicillin. However, no such protection was present following the administration of cefprozil. Furthermore, the preservation of S. salivarius that interferes with GABHS growth may provide protection from reinfection with GABHS. This study supports and provides an explanation for the increased efficacies of cephalosporins administered orally over that of penicillin when treating patients with acute GABHS pharyngitis or tonsillitis. PMID- 8363376 TI - Characterization of the aac(6')-Ib gene encoding an aminoglycoside 6'-N acetyltransferase in Pseudomonas aeruginosa BM2656. AB - Pseudomonas aeruginosa BM2656 was resistant to tobramycin and susceptible to gentamicin and amikacin by disk diffusion testing. This unusual resistance was not transferable by conjugation to Escherichia coli or P. aeruginosa PAO38, and plasmid DNA was not detected in this strain. A 0.9-kb fragment harboring the tobramycin resistance gene was cloned from BM2656 into pUC18, generating pAT129. Analysis for aminoglycoside-modifying activity in extracts of BM2656 and E. coli harboring pAT129 indicated that tobramycin resistance was due to synthesis of an aminoglycoside 6'-N-acetyltransferase type I [AAC(6')-I] enzyme which modified amikacin and tobramycin. Although amikacin was acetylated, the bactericidal synergism of this aminoglycoside with ceftazidime against BM2656 was minimally affected. The sequence of the DNA fragment was determined. It contained an aac (6')-Ib-like gene and was located downstream from a conserved region related to Tn21. The translated sequence of this aac(6')-Ib gene possessed 99.2% identity with the putative products of the aac(6')-Ib gene cassettes from Serratia marcescens and Klebsiella pneumoniae and 69% identity with the putative aacA(6') II gene product from P. aeruginosa. We conclude that an aac(6')-Ib gene has spread to the chromosome of P. aeruginosa, probably by transposition. PMID- 8363377 TI - Facilitation of penicillin haptenation to serum proteins. AB - Traditionally, penicillin binding to serum proteins was believed to be a passive chemical process; however, it appears to be facilitated by serum factors. The objectives of this in vitro investigation were to examine facilitated penicillin haptenation, to study the kinetics of haptenation, and to determine the nature of haptenation-facilitating factors. The model involved addition of [3H]benzylpenicillin to serum or albumin solutions (at pH 7.3 to 7.4) and incubation at 37 degrees C for up to 72 h. The extent of penicillin binding to proteins in serum was found to be four- to fivefold higher than with solutions having comparable concentrations of purified albumin, total protein, or total immunoglobulin. Ultrafiltration of serum reduced penicillin binding to serum proteins substantially. An ultrafiltrable haptenation-facilitating factor(s) was found to be less than 0.5 kDa but was not calcium or magnesium. Finally, the extent of penicillin binding was related to albumin purity, as binding substantially increased with albumin purity. These findings suggest that there is a factor(s) in serum that facilitates covalent binding of penicillin to serum proteins. The factor(s) can be removed and then restored to increase penicillin binding to albumin. It appears that at least one component of the facilitation factor is less than 0.5 kDa, which suggests that it is not a peptide and that it is some simple serum component other than calcium or magnesium. PMID- 8363378 TI - Bioequivalence of oral and intravenous ofloxacin after multiple-dose administration to healthy male volunteers. AB - The bioequivalence of oral and intravenous ofloxacin was investigated after the administration of multiple doses of 400 mg every 12 h to 20 healthy male volunteers in a randomized, crossover, open-label study. Ofloxacin concentrations in plasma were evaluated after 4 days of oral or intravenous (1-h infusion) dosing with a 3-day wash-out period between regimens. As expected, delivery to the systemic circulation took slightly longer after the oral dosing (time to maximum concentration of drug in serum of 1.7 h) relative to the 1-h intravenous infusion, but the systemic availabilities of ofloxacin by the two routes of administration were equivalent (area under the concentration-time curve from 0 to 12 h ratio of 95%). Since previous studies have not demonstrated any change in the bioavailability of ofloxacin in infectious disease patients, this study supports the interchangeability of these dosing regimens. PMID- 8363379 TI - 4-Guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and B viruses in vitro. AB - The sialidase (neuraminidase) inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N acetylneuraminic acid (4-guanidino-Neu5Ac2en) has been examined for the ability to inhibit the growth of a wide range of influenza A and B viruses in vitro in comparison with amantadine, rimantadine, and ribavirin. 4-Guanidino-Neu5Ac2en inhibited plaque formation by laboratory-passaged strains of influenza A and B viruses, with 50% inhibitory concentrations ranging from 0.005 to 0.014 microM. A wider range of values (0.02 to 16 microM) was obtained with more recent clinical isolates, but in all cases 4-guanidino-Neu5Ac2en inhibited influenza A and B virus replication at lower concentrations than amantadine, rimantadine, or ribavirin. Inhibition by 4-guanidino-Neu5Ac2en was not obviously affected by the passage history of the viruses or by resistance to amantadine or rimantadine. 4 Guanidino-Neu5Ac2en was a very potent inhibitor of the sialidases of all the influenza viruses examined, with 50% inhibitory concentrations ranging from 0.00064 to 0.0079 microM. No cytotoxicity was observed with 4-guanidino-Neu5Ac2en at up to 10 mM. 4-Guanidino-Neu5Ac2en therefore represents a new potent and selective inhibitor of influenza A and B virus sialidase activity and replication in vitro. PMID- 8363380 TI - Biliary excretion of cefixime: assessment in patients provided with T-tube drainage. AB - The biliary excretion profile of cefixime was studied in 10 patients provided with T-tube drainage of the common bile duct after cholecystectomy. Following a single 200-mg oral dose, the peak concentration of cefixime in bile reached 56.9 +/- 70 mg/liter, approximately 20 times as high as the peak concentration in serum, 2.3 +/- 0.85 mg/liter. Cefixime levels in bile proved relatively sustained, since a concentration of 4.3 +/- 3.7 mg/liter was still found 20 h after dosing. The cumulative amount of cefixime recovered in the 24-h bile drainage averaged 10.0 +/- 12.3 mg, which is 5% of the administered dose and positions this beta-lactam antibiotic among the most highly bile-excreted cephalosporins. The presented results show that a single 200-mg oral dose of cefixime provided drug levels in bile consistently higher than the MICs for the most frequently recovered members of the family Enterobacteriaceae in biliary tract infections and maintained these levels for over 20 h after dosing. Accordingly, this cephalosporin deserves further clinical trials to assess its usefulness in both prophylaxis and treatment of biliary tract infections. PMID- 8363381 TI - Activity of bilobalide, a sesquiterpene from Ginkgo biloba, on Pneumocystis carinii. AB - The sesquiterpene bilobalide, extracted from Ginkgo biloba leaves, was tested in vitro and in vivo for the ability to inhibit Pneumocystis carinii growth. Bilobalide was inhibitory to trophozoites cultured on human embryonic lung fibroblasts (HEL 299) at approximately the same concentration as trimethoprim plus sulfamethoxazole (lowest effective concentration, 50 micrograms of bilobalide per ml versus 9/45 microgram of trimethoprim-sulfamethoxazole per ml), inducing microscopically detectable morphological changes in the cytoplasm of the parasite. In pharmacologically immunosuppressed Sprague-Dawley rats transtracheally infected with a suspension of about 5 x 10(6) P. carinii trophozoites per ml, the daily intraperitoneal administration of bilobalide (10 mg/kg of body weight for 8 days) lowered the number of organisms by approximately 2 logs (that is, about 99%). There was no apparent toxicity either in uninfected HEL 299 feeder cells or in infected and uninfected animals. These studies suggest that the sesquiterpene bilobalide might be useful for therapy of and prophylaxis against P. carinii infections in humans. PMID- 8363382 TI - Treatment of experimental visceral leishmaniasis in a T-cell-deficient host: response to amphotericin B and pentamidine. AB - In experimental visceral leishmaniasis, euthymic but not athymic (nude) BALB/c mice respond to conventional treatment with pentavalent antimony, indicating that the in vivo efficacy of antimony is T cell dependent. This finding correlates with frequent antimony treatment failures for T-cell-deficient patients with visceral leishmaniasis. To determine whether the in vivo efficacies of alternative antileishmanial agents also require T cells, Leishmania donovani infected euthymic and nude BALB/c mice were treated with pentamidine or amphotericin B. Pentamidine induced leishmanistatic activity in euthymic mice but had little effect in nude mice. In contrast, amphotericin B exerted potent leishmanicidal activities in both euthymic and nude animals. These results suggest that amphotericin B may be of particular use for T-cell-deficient patients with visceral leishmaniasis. PMID- 8363383 TI - Local gastric and serum amoxicillin concentrations after different oral application forms. AB - The high recolonization rate after monotherapy of Helicobacter pylori-positive gastritis may be due to insufficient local drug concentrations. To investigate the role of local diffusion, we measured levels of amoxicillin, a drug with good in vitro activity against H. pylori, in the mucosa and serum. One gram of amoxicillin was given to healthy volunteers as a tablet (n = 6) or as water dissolved, fizzing "Tab" (n = 6). Gastroscopy with biopsies from the antrum, corpus, and fundus was performed at 30, 60, and 90 min. Concentrations in the mucosa were measured after homogenization with the agar diffusion method using Bacillus subtilis as the biological indicator. Serum samples, taken basally and every 15 min, were analyzed by high-pressure liquid chromatography. Drug levels in the fundus and corpus remained far below those in the antrum for both application forms. The highest concentrations were reached after 30 min, with bactericidal levels in the antrum in two of six subjects who took the tablet form and five of six subjects who used Tabs. At 60 and 90 min, almost all values were below the MBC for 90% of the strains tested. The concentrations in serum, however, rose continuously, to reach a maximum after 75 or 90 min. These results show that incomplete elimination may be due to subbactericidal concentrations of antibiotics with high in vitro efficiency at the desired site of action in vivo and that local diffusion in the mucosa is essential for therapeutic effectiveness against H. pylori. PMID- 8363385 TI - Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges. AB - Cefotaxime and ceftriaxone have proven to be effective in pyogenic infections of the central nervous system. Since in some bacterial central nervous system infections the blood-cerebrospinal fluid (CSF) barrier is either minimally impaired or recovers in the course of the illness, we studied the penetration of both antibiotics in the absence of inflamed meninges. Patients who had undergone external ventriculostomies for noninflammatory occlusive hydrocephalus received either cefotaxime (2 g/30 min) or ceftriaxone (2 g/30 min) to treat extracerebral infections. Serum and CSF were drawn repeatedly after the first dose. With ceftriaxone, they were also drawn after the last dose. The concentrations of cefotaxime, its metabolite desacetylcefotaxime, and ceftriaxone were determined by high-performance liquid chromatography with UV detection. Maximum concentrations of cefotaxime in CSF were reached 0.5 to 8 h (median = 3 h; n = 6) after the end of the infusion and ranged from 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum levels of ceftriaxone in CSF ranging from 0.18 to 1.04 mg/liter (median = 0.43 mg/liter; n = 5) were seen 1 to 16 h (median = 12 h; n = 5) after the infusion. The elimination half-life of cefotaxime in CSF was 5.0 to 26.9 h (median = 9.3 h; n = 5), and that of ceftriaxone was 15.7 to 18.4 h (median = 16.8 h; n = 3). It is concluded that after a single dose of 2 g, maximal concentrations of cefotaxime and ceftriaxone in CSF do not differ substantially. The long elimination half-lives guarantee uniform concentrations in CSF. These concentrations reliably inhibit highly susceptible bacteria but cannot be relied on to inhibit staphylococci and penicillin G-resistant Streptococcus pneumoniae. PMID- 8363386 TI - Use of cephalosporins for prophylaxis and therapy of polymicrobial infection in mice. AB - Cefoxitin, cefotetan, and cefmetazole were compared in 10-day therapy of intra abdominal and subcutaneous infections caused by three organisms: Bacteroides fragilis and Bacteroides thetaiotaomicron combined with either Escherichia coli or Staphylococcus aureus. Intra-abdominal infection was caused by B. fragilis plus B. thetaiotaomicron plus E. coli. Therapy was initiated immediately before inoculation or was delayed for 8 h. Mortality was 14 of 30 (47%) for saline treated mice, and all survivors developed abscesses. Immediate therapy reduced mortality and the percentage of mice with abscesses (in survivors), respectively, to 17 and 20% with cefoxitin, 0 and 13% with cefotetan, and 0 and 17% with cefmetazole, and the numbers of all bacteria were reduced by all the cephalosporins. Delayed therapy reduced mortality and abscess formation, respectively, to 20 and 8% of mice with cefoxitin, 10 and 93% with cefotetan, and 7 and 96% with cefmetazole. B. thetaiotaomicron survived in all abscesses treated with cefotetan and cefmetazole. Subcutaneous abscesses were caused by each organism alone or in combinations of one aerobe (S. aureus or E. coli) and one or two Bacteroides species. Early therapy reduced the numbers of all bacteria independent of their in vitro susceptibility. All agents reduced the number of each Bacteroides species with either E. coli or S. aureus. However, when therapy was delayed, cefotetan and cefmetazole were less effective than cefoxitin against B. thetaiotaomicron. Cefotetan was the most active agent against E. coli, and cefmetazole was the most effective against S. aureus. These data illustrate the efficacy of all tested cephalosporins in the prophylaxis of polymicrobial infections. PMID- 8363384 TI - Gentamicin administered during gestation alters glomerular basement membrane development. AB - Gentamicin during gestation alters glomerular basement membrane development. A drug-induced nephrotoxicity was described for neonates after gentamicin was given intraperitoneally to pregnant Wistar rats; glomerular alterations and changes in permselectivity were important. We investigated the ultrastructure of the glomerular basement membrane (GBM), the arrangement of anionic sites, and the urinary proteins at two ages, with 1-day- and 12-month-old control and prenatally exposed animals. For neonates, the pattern of glomerular differentiation was similar, anionic sites were made of heparan sulfate proteoglycans, and the GBM had the same total thickness in both groups. After transplacental gentamicin exposure, the lamina densa was larger; the laminae rarae were thinner; the density of anionic sites was increased; the levels of hydroxyproline, sulfate, and hexuronic acid in the kidney were increased; and the immunoelectrophoresis of urinary proteins was abnormal. For adults, prenatal exposure to gentamicin led to altered juxta-medullary glomeruli with a larger GBM and abundant anionic sites, especially in the lamina densa, and to a protein excretion different from that of controls. Thus, gentamicin administered during pregnancy leads to permanent alterations of the GBM with modifications of both the layers and the anionic sites, possibly because of a perturbed protein metabolism. These altered glomeruli are at risk during life and could be the starting point for a kidney disease. PMID- 8363387 TI - Ethambutol inhibition of glucose metabolism in mycobacteria: a possible target of the drug. AB - The addition of D-arabinose, D-galactose, D-glucosamine, or D-mannose to the growth medium of Mycobacterium smegmatis suppressed the inhibitory effects of ethambutol both on acetate labeling of cell wall-linked mycolic acids and on the increase in the delipidated cell dry weight. The addition of D-glucose or D fructose had no effect. It is proposed that ethambutol inhibits an early step of glucose conversion into the monosaccharides used for the biosynthesis of structurally and biologically important cell wall polysaccharides: arabinogalactan, arabinomannan, and peptidoglycan. PMID- 8363388 TI - Suramin prevents duck hepatitis B virus infection in vivo. AB - The effect of suramin on duck hepatitis B virus (DHBV) infection was investigated in vivo. Suramin pretreatment of Pekin ducklings completely prevented DHBV infection. In contrast, suramin given at the time of or after inoculation with DHBV did not inhibit viral infection, replication, or gene expression. These data indicate that suramin effectively blocks the early stages of DHBV infection in vivo. PMID- 8363389 TI - In vitro antibacterial activity and beta-lactamase stability of CP-70,429 a new penem antibiotic. AB - In in vitro susceptibility tests, the new penem CP-70,429 showed potent antibacterial activity against gram-positive and gram-negative bacteria except Pseudomonas aeruginosa and Xanthomonas maltophilia. CP-70,429 was stable to various types of beta-lactamases except for the enzyme from X. maltophilia and was 16- to 128-fold more active than the other compounds against beta-lactamase producing strains of Enterobacter cloacae and Citrobacter freundii. PMID- 8363391 TI - Ciprofloxacin susceptibility testing by MIC and disk elution of drug-resistant Mycobacterium tuberculosis and Mycobacterium avium complex. AB - The ability to provide susceptibility data for certain species of mycobacteria can be clinically useful. In this study, the disk elution method for susceptibility testing was adapted for testing ciprofloxacin against mycobacterial isolates. Of the 75 Mycobacterium tuberculosis isolates tested, including 23 multiply drug-resistant isolates, 96% were susceptible to ciprofloxacin at a breakpoint concentration of 2 micrograms/ml. PMID- 8363390 TI - In vitro susceptibilities of isolates of Haemophilus ducreyi from Thailand and the United States to currently recommended and newer agents for treatment of chancroid. AB - We determined the in vitro susceptibilities of 54 isolates of Haemophilus ducreyi from Thailand (29 isolates) and San Francisco (25 isolates) to penicillin G, tetracycline, amoxicillin-clavulanic acid, ceftriaxone, cefixime, erythromycin, azithromycin, ciprofloxacin, ofloxacin, and trimethoprim-sulfamethoxazole. Isolates were susceptible to < or = 0.25 microgram of ceftriaxone per ml, < or less 0.5 microgram of cefixime per ml, < or = 0.125 microgram of ciprofloxacin per ml, and < or = 0.06 microgram of ofloxacin per ml. Erythromycin was active against all isolates (MIC for 90% of isolates tested, 0.25 microgram/ml), as was azithromycin (MIC, < or = micrograms/ml). In contrast, all but one isolate were resistant to > or = 8.0 micrograms of tetracycline per ml, 11.1% of the isolates were resistant to and 40.9% of the isolates were resistant to trimethoprim sulfamethoxazole (MIC, > or = 4/76 microgram/ml.) PMID- 8363392 TI - Enoxacin relieves symptoms of recurrent urinary infections more rapidly than cefuroxime axetil. AB - In patients with a history of recurrent infections, treatment with enoxacin (200 mg/12 h for 3 days) relieved symptoms of acute urinary infection significantly more rapidly than treatment with cefuroxime axetil (125 mg/12 h for 7 days). Other parameters, including clinical and bacteriological cure rates and patients' overall opinion of their treatment, did not differ significantly between the treatments. PMID- 8363393 TI - In vitro activity of roxithromycin against 16 species of atypical mycobacteria and effect of pH on its radiometric MICs. AB - The antimycobacterial spectrum of roxithromycin, a semisynthetic 14-membered ring macrolide, was determined against 28 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs by BACTEC methodology at two different pH values, i.e., 6.8 and 7.4. The MICs obtained at pH 7.4 were 1 to 2 dilutions lower or more than those obtained at pH 6.8 for some of the species. Roxithromycin possessed promising MICs against such potential pathogens as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, and rare pathogens like M. chelonei subsp. chelonei and M. chelonei subsp. abscessus but not against M. simiae. Roxithromycin showed lower MICs against M. fortuitum var. peregrinum than M. fortuitum var. fortuitum. PMID- 8363394 TI - The role of magnetic resonance imaging in the diagnostic evaluation of dermatomyositis. PMID- 8363395 TI - Citation classics in clinical dermatologic journals. Citation analysis, biomedical journals, and landmark articles, 1945-1990. AB - BACKGROUND AND DESIGN: Analysis of the most frequently cited dermatology articles and the journals in which they appear identifies and emphasizes the impact of works of colleagues and predecessors, recognizes key advances in cutaneous medicine and surgery, and adds useful data about historical developments in dermatology. Use of citation analysis to examine the dermatologic literature reveals quantitative information about authors, articles, and journals helpful in identifying classic works and high-impact journals. We analyze the characteristics of all dermatology articles cited 100 or more times in one of the 10 most highly ranked clinical dermatology journals as indicated by the Institute of Scientific Information (Philadelphia, Pa) database from 1945 through 1990 and also discuss the standard and, as well, more recently described bibliometric indexes for dermatologic journals. RESULTS: Thirty-one institutions located in 11 different countries produced 129 landmark articles. Ninety-two percent of the citation classics originated in the United States, United Kingdom, Sweden, and Germany. There were 16 authors with three or more top-cited articles. Fifty-two percent of the articles were of the clinical type, 22% were clinical review articles, and 26% discussed basic science topics. The mean number of authors has increased gradually over the past 80 years. The average classic article was published in 1969, peaked in popularity 9 years later with 26 peer citations, and received only 11 citations in 1990. CONCLUSIONS: Citation frequency and citation analysis reveal useful and interesting information about scientific communication. The data on citation classics we describe can be interpreted in many ways, but certainly reflects the attention that articles have received over the past 48 years. The half-life of the average citation classic of about 10 years reflects the rapid pace of advances in the science and practice of dermatology over the past several decades. This information, along with current bibliometric indexes, may assist physicians in optimizing the time they spend reading the medical literature. PMID- 8363396 TI - Association of tissue-fixed cytoplasmic deposits of immunoglobulin in epidermal keratinocytes with lupus erythematosus. AB - BACKGROUND AND DESIGN: We have observed that tissue-fixed deposits of immunoglobulin (Ig) are occasionally present in the cytoplasm (CYT) of epidermal keratinocytes. This study was conducted to examine the frequency, significance, and possible cause of this finding. RESULTS: Direct immunofluorescence studies were performed on 302 sequential skin specimens obtained from patients with lupus erythematosus (n = 98), bullous diseases (n = 114), or other dermatoses (n = 90). Abnormal epidermal CYT deposits were observed in 22 of the patients with lupus erythematosus (22.5%), four of those with bullous diseases (3.5%), and two of those with other dermatoses (2.2%). The deposits were more common in systemic than in discoid lupus erythematosus, and in skin lesions than in normal skin. By indirect immunofluorescence, circulating antibodies to epidermal upper CYT antigens were present in 100% of 12 patients with tissue-fixed CYT deposits (average antibody titer, 300) and in 21% of 19 individuals without CYT deposits (average titer, 43). By Western immunoblot analysis these antibodies were directed to proteins in keratin extracts of skin. CONCLUSIONS: These findings indicate that deposits of Ig in the cytoplasm of keratinocytes in human skin are associated with high levels of serum antibodies to upper CYT antigens and with lupus erythematosus. PMID- 8363397 TI - Aneuploid malignant T cells from a patient with Sezary syndrome can be visualized by in situ hybridization. AB - BACKGROUND AND DESIGN: Enumeration of malignant cells in Sezary syndrome often relies on the identification of the Sezary cell nucleus. This morphologic method is, however, nonspecific and unreliable in the enumeration of the proportion of malignant lymphocytes in peripheral blood of patients with Sezary syndrome. Malignant lymphocytes of patients with mycosis fungoides and Sezary syndrome are often characterized by multiple chromosome aberrations. Herein, we demonstrate that fluorescent in situ hybridization can visualize and accurately enumerate malignant aneuploid mononuclear cells in a patient with Sezary syndrome. RESULTS: Fluorescent in situ hybridization demonstrated that 90% of the mononuclear cells in the patient with Sezary syndrome showed numerical aberrations for both chromosome 7 and X, a figure confirmed by flow cytometry. CONCLUSION: Fluorescent in situ hybridization may be a valuable tool to visualize and enumerate aneuploid tumor cells in patients with cutaneous T-cell lymphoma. PMID- 8363398 TI - Outcomes of cryosurgery in keloids and hypertrophic scars. A prospective consecutive trial of case series. AB - BACKGROUND AND DESIGN: A variety of therapeutic regimens has been used in keloids and hypertrophic scars with unsatisfactory final results. Application of cryosurgery could be beneficial since it was reported to produce less scarring after treatment of skin tumors compared with other surgical procedures. We performed a prospective consecutive trial of randomly enrolled case series including 32 months of average follow-up to assess the outcomes of cryosurgical treatment in keloids and hypertrophic scars and to determine factors influencing the therapeutic result. Ninety-three white patients, aged 10 to 79 years (median age, 26 years) with keloids (n = 55; median duration, 36 months; median size, 4 cm2) and with hypertrophic scars (n = 38; median duration, 12 months; median size, 2 cm2) were treated using the contact method. One freeze-thaw cycle of 30 seconds per lesion and session was employed, and, if needed, treatment was repeated every 20 to 30 days. RESULTS: Excellent responses (ER) were recorded in 30 subjects (32.3%), good responses (GR) in 27 (29.0%), poor responses (PR) in 27 (29.0%), while nine subjects (9.7%) did not respond at all. Hypertrophic scars responded better (n = 38; GR to ER, 76.3%) than keloids (n = 55; GR to ER, 50.9%; P < .005; odds ratio, 6.92). No progressions or recurrences occurred. Histologically, neovascularization, loss of the anarchic arrangement of collagen bundles, increased fibroblasts in a stroma running parallel to the skin surface, and mononuclear cells mostly arranged at the perivascular area were found in clinically responding lesions. Improved responses were detected in subjects treated with three or more sessions (n = 57; GR to ER, 78.9%) compared with subjects treated once or twice (n = 36; GR to ER, 33.3%; P < .001; odds ratio, 13.68). The cryosurgical treatment was generally well tolerated, with local pain during freezing and/or shortly after treatment (n = 32, 34.4%) and hypopigmentation or hyperpigmentation (n = 11, 11.8%) being the most frequent side effects. CONCLUSIONS: Cryosurgery was found effective and safe in keloids and, especially, in hypertrophic scars, in an open, uncontrolled study. Satisfactory results could be obtained after at least three cryosurgical sessions of 30 seconds each, applied once monthly using the contact method of treatment. PMID- 8363399 TI - Pretibial mucin. Histologic patterns and clinical correlation. AB - BACKGROUND AND OBJECTIVE: We identified several patients with a histologic diagnosis of pretibial myxedema in whom thyroid disease was not found. The purpose of this study was to investigate if histologic characteristics can distinguish between pretibial mucinosis secondary to Graves' disease and that unassociated with thyroid disease. METHODS: Biopsy specimens interpreted as compatible with pretibial myxedema were reviewed; these included 12 cases of pretibial mucinosis with documented Graves' disease, and six cases of pretibial mucinosis without evidence of Graves' disease. Ten specimens interpreted as compatible with stasis dermatitis were also evaluated for histologic characteristics, including the possible presence of mucin. RESULTS: Features that distinguish between pretibial mucinosis associated with Graves' disease and pretibial mucinosis without Graves' disease included preservation of a zone of normal-appearing collagen in the superficial papillary dermis (12/12 with Graves' disease, 0/6 without), mucin deposition in the reticular dermis (12/12 with Graves' disease, 0/6 without), lack of mucin deposition in the superficial papillary dermis (11/12 with Graves' disease, 1/6 without), angioplasia (2/12 with Graves' disease, 6/6 without), and the presence of hemosiderin (2/12 with Graves' disease, 6/6 without). Mucin deposition in the papillary dermis was found in six of 10 specimens interpreted as stasis dermatitis. CONCLUSIONS: There are patients with pretibial mucinosis in whom there is no thyroid disease. Specimens from patients without Graves' disease have features of stasis dermatitis in addition to mucinosis. We conclude that pretibial mucinosis may result from stasis or Graves' disease and that histologic differences allow for accurate differentiation. PMID- 8363400 TI - Expression of p53 protein is an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis. AB - BACKGROUND AND DESIGN: p53 Is known to be a tumor-suppressor gene and has been suggested to play an important role for multistep carcinogenesis of cutaneous squamous cell carcinoma (SCC). To evaluate the role of ultraviolet light (UV) in p53 mutation in squamous cell carcinogenesis, paraffin-embedded sections of SCCs were immunohistochemically stained with the CM-1 antibody for p53 protein. Positive staining suggests mutation of the p53 gene since the mutant p53 protein gains prolonged half-life to be detectable by this method. The specimen included SCCs induced by UV (SCCs on sun-exposed areas, SCCs on patients with xeroderma pigmentosum), roentgen rays, scar, and miscellaneous causes. In addition, solar keratoses that are precancerous lesions of UV-related SCCs were also analyzed. RESULTS: Fourteen (54%) of 26 UV-related SCCs were positive, whereas five (19%) of 26 UV-unrelated SCCs were positive. Among the UV-related SCCs, five (45%) of 11 well-differentiated SCCs and nine (60%) of 15 moderately to poorly differentiated SCCs were positive. Eleven (48%) of 23 solar keratoses were positive for p53. CONCLUSIONS: These results indicate that UV acts as a mutagen for the p53 gene, and this event may occur at a relatively early stage of multistep UV carcinogenesis. PMID- 8363401 TI - Radiation therapy of giant aggressive keratoacanthomas. AB - BACKGROUND AND DESIGN: Giant aggressive keratoacanthoma is a rare destructive subset of keratoacanthoma that frequently involves the facial region, grows rapidly to a large size, and often recurs after surgical management. The effectiveness of ionizing radiation therapy was examined in a retrospective study involving 16 patients; 14 of the tumors had recurred after surgical therapy. RESULTS: All tumors resolved with satisfactory cosmetic results and without recurrence following a fractionated course of superficial radiation therapy. CONCLUSIONS: Radiation therapy is an effective therapeutic modality for giant aggressive keratoacanthomas. PMID- 8363402 TI - Serum soluble interleukin 2 receptor levels in erythrodermic cutaneous T-cell lymphoma correlate with response to photopheresis-based treatment. AB - BACKGROUND: Cutaneous T-cell lymphoma (CTCL) comprises a spectrum of presentations, including erythroderma, pruritus, lymphadenopathy, and circulating atypical lymphocytes. Photopheresis is an extracorporeal treatment in which white blood cell concentrates are subjected to UV irradiation when the serum methoxypsoralen level is above 50 ng/mL. Of patients with CTCL, those with erythroderma have been most responsive to this therapy. In some conditions, including certain malignant hematologic neoplasms, serum soluble interleukin 2 receptor levels (SIL2R) correlate with disease activity. We sought to determine whether serum SIL2R levels correlated with disease activity in six erythrodermic patients with CTCL treated primarily with photopheresis. We measured SIL2R levels in five patients with stage III or greater erythrodermic CTCL and one with stage IIa CTCL. We compared SIL2R values with clinical course, skin scores, CD4/CD8 ratios, peripheral white blood cell counts, and Sezary cell counts, using Pearson correlation coefficients. OBSERVATIONS: The SIL2R levels correlated with clinical course and skin scores, even when controlled for other factors noted above. CONCLUSION: Data preliminarily suggest that serum SIL2R levels may be useful indicators of disease activity in erythrodermic CTCL patients treated with photopheresis. PMID- 8363404 TI - The Archives of Dermatology annual trainee award. PMID- 8363403 TI - Subcutaneous T-cell lymphoma. Report of two additional cases and further observations. AB - BACKGROUND: Peripheral T-cell lymphomas involving subcutaneous tissue are rare. With modern immunohistochemical stains, subcutaneous T-cell lymphomas may be demonstrated in patients previously thought to have fatal Weber-Christian disease, malignant histiocytosis, and histiocytic cytophagic panniculitis. OBSERVATIONS: We describe two young women with subcutaneous lymphomas. They presented with erythematous nodular lesions, which suggested benign panniculitis. Skin biopsy specimens in both patients demonstrated large atypical lymphocytes in the subcutaneous tissue, karyorrhexis, and cytophagia. Immunohistochemical studies confirmed a T-cell phenotype. Molecular genetics studies performed in one patient showed a major T-cell clonal population. CONCLUSIONS: Subcutaneous T-cell lymphoma is a rare, distinct subtype of postthymic peripheral T-cell lymphoma. Cytophagic "histiocytic" panniculitis is frequently a prominent histologic feature. Early systemic chemotherapy may offer therapeutic advantages in patients with this disease. PMID- 8363405 TI - Considering excellence. PMID- 8363406 TI - Papular lesions in an immunocompromised patient. Trichophyton rubrum granulomas (Majocchi's granuloma). PMID- 8363407 TI - Ichthyosiform rash and fever in a child. Tinea corporis and capitis due to Trichophyton tonsurans. PMID- 8363408 TI - Multiple cutaneous ulcers of the legs. Mycobacterium chelonae infection. PMID- 8363409 TI - Subcutaneous nodule in a cardiac transplant. Cutaneous aspergillosis. PMID- 8363410 TI - Controlled trial of azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous pemphigoid. PMID- 8363411 TI - Chronic skin ulcers and the biology of skin grafts. PMID- 8363412 TI - Clinical pharmacology. PMID- 8363413 TI - Malignant melanoma of unknown origin presenting as a systemic vasculitis. PMID- 8363414 TI - A cutaneous lesion associated with primary polymyositis. PMID- 8363415 TI - Lentigo maligna is more common on the driver's side. PMID- 8363416 TI - Malignant melanoma and a squamous cell carcinoma in recessive dystrophic epidermolysis bullosa. PMID- 8363417 TI - Malignant melanoma arising from a small congenital nevus in a black child. PMID- 8363418 TI - Transverse white lines in the fingernails induced by combination chemotherapy. PMID- 8363419 TI - [20 years of mitral valve replacement. Development of a patient profile and operative mortality]. AB - Between 1971 and 1991, 1,179 mitral valve replacements (MVR) were carried out in 1,134 patients. The sex ratio was stable over this period (0.7 men/women) whereas the average age of the patients increased by 10 years (50 years in 1971, 61 years in 1991). Since 1980, patients over 60 years of age represent about 60% and those over 70 years of age 16 to 22% of the population. The functional status of the patients has tended to be less severe, the NYHA stages III and IV which were initially preponderant, only represent 50 to 60% of patients operated nowadays. This reduction in the severity of symptoms is reflected in the average value of the cardio thoracic index which was 60 in 1971 and 54.8 in 1991. Similarly, the mean pulmonary artery pressures (measured in 823 patients, 69.8%) have decreased from 37.4 mmHg in 1971 to 29.9 mmHg in 1991. Rheumatic fever has tended to be replaced by degenerative etiologies which, since 1985, represent 40 to 50% of cases. Ischemic mitral regurgitation rare before 1980, is more common, presently making up 5 to 15% of MVR cases. In relation with the etiological changes mitral stenosis is giving way to mitral regurgitation as the commonest valve lesion (40 to 50% of cases in 1991). The annual operative mortality is lower (6 to 8%) than in 1982, despite the increasing number of emergency cases (7 to 10% of cases since 1985). The number of MVR with associated tricuspid valve repair has decreased with respect to isolated MVR or associated with aortocoronary bypass grafting. The only constant feature is the death rate due to myocardial dysfunction which remains over 50% whereas mortality related to the prosthetic valves varied over the years. PMID- 8363421 TI - [Incidence of inducible supraventricular tachycardia in dysplasia of the right ventricle]. AB - Arrhythmogenic right ventricular dysplasia (ARVD) is classically associated with ventricular tachycardia and the prevalence of supraventricular tachycardia in this condition is not well known. The aim of this study was to observe the response of 20 patients with ARVD to programmed atrial stimulation and compare it with 150 subjects without cardiac disease or spontaneous supraventricular tachycardia. The protocol used 2 atrial extra-stimuli delivered on 3 paced cycles. Programmed atrial stimulation with 1 extrastimulus was repeated after infusion of 20 to 30 micrograms of Isoproterenol. Sustained supraventricular tachycardia could be induced in 13 patients with ARVD (65%) and 17 control subjects (11%) (p < 0.001). It was not possible to distinguish patients with inducible supraventricular tachycardia from those without inducible arrhythmias by electrophysiologic parameters. Isoproterenol facilitated the induction of VT but not supraventricular tachycardia. Three patients with inducible supraventricular tachycardia developed spontaneous atrial fibrillation. In conclusion, there is a relatively high incidence of inducible supraventricular tachycardia in ARVD: Isoproterenol does not facilitate this tachycardia, contrary to ventricular tachycardia. PMID- 8363420 TI - [Mitral valvuloplasty during the acute phase of endocarditis]. AB - Thirty-five patients were operated in the acute phase of mitral valve endocarditis between 1986 and 1991. The surgical indications were hemodynamic (22), echocardiographic (9), embolic (2) and infectious (2). There were pre existing valve lesions in 45% of cases. The causal organism was identified in 90% of cases: streptococcus (19), staphylococcus (9) and Gram negative bacilli (4). Preoperative antibiotic therapy was prescribed for an average of 18 days. The aortic valve was infected in 9 patients and tricuspid valve in 1 patient. The mitral lesions were: abscess (11), vegetations (11), perforations (16), and ruptured chordae tendinae (22). All patients underwent Carpentier's mitral valvuloplasty. The operative mortality was 5.7% (2 patients). Early reoperation was required in 1 case. Follow-up was possible in 96% of cases for an average of 23 months. No recurrences of endocarditis were observed. One patient was reoperated and 3 died. All the others were in Classes I and II of the NYHA. None had significant mitral regurgitation or stenosis. These results show that mitral valvuloplasty is possible in the acute phase of endocarditis in 90% of cases. The mortality and morbidity are low and long-term results are stable. PMID- 8363422 TI - [Myocardial infarction treated within 4 hrs: comparison of the cost-benefit ratio of 3 thrombolytic treatments: APSAC, rt-PA and streptokinase in 270 patients]. AB - Two hundred and seventy patients under 71 years of age with myocardial infarction less than 4 hours old, defined by clinical and electrocardiographic criteria, were included in this trial and followed up for 1 year: two groups of 89 and 92 patients were randomised to receive APSAC (30 mg i.v. over 5 minutes) or rt-PA (10 mg bolus + 5000 IU of heparin as a bolus, followed by 90 mg rt-PA over 3 hours) and compared with a control series of 89 consecutive patients treated with streptokinase (1.5 MU in 1 hour). Heparin and aspirin (250 mg/day) were prescribed systematically. A score of efficacy was established from the following 4 parameters: patency of the infarct-related artery on coronary angiography at day 6 +/- 2 (N = 252), dyssynergic score on radiological ventriculography, infarct size on resting Thallium myocardial scintigraphy performed between day 15 and 21 (N = 242) and radionuclide ejection fraction performed at the same time. This score (0-24) was respectively 17.8 +/- 6.4 for rt-PA, 17.7 +/- 6.0 for APSAC and 18.1 +/- 6.0 for streptokinase (NS). The costs of hospital treatment were assessed by including: the cost of thrombolytic therapy (ranging from 1.7% of total cost for streptokinase to 16% for rt-PA), the cost of other treatments and biological investigations (10% of total cost); the cost of followed coronary angiography, in 33% of patients, by an angioplasty (21% of total cost), the cost of hospital stay averaging 17 days (49% of total cost in the rt-PA and APSAC groups and 56% in the streptokinase group NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363423 TI - [Initial experience of percutaneous catheter ablation using radiofrequency of atrioventricular accessory pathways]. AB - This paper reports the authors' preliminary experience in catheter ablation by radiofrequency current of 46 accessory atrioventricular pathways in 45 symptomatic patients with supraventricular tachyarrhythmias resistant to medical therapy. With an average follow-up period of 5.5 +/- 4 months the global success rate was 80%, ranging from 96% in left lateral to 33% in antero septal accessory pathways. It increased from 65% in the first 20 patients to 88% in the last 25 patients. The average duration of radioscopy was significantly shorter in left lateral pathways than in other localisations (p < 0.02); it was also shorter when ablation was successful. Complications were observed in 4 patients (9%) and included one complete atrioventricular block and 3 femoral arterial lesions. Anaesthetic assistance was required in 14 cases (31%), either at the patient's request or to allow reduction of atrial fibrillation. Percutaneous catheter ablation of accessory atrioventricular pathways with radiofrequency current is effective and gives good results; very strict selection of initial patients and the respect of certain conditions taking into account the experience of the medical team, the technically difficult approach of certain accessory pathways and the risks of ablation of pathways running near the atrioventricular node or His bundle, are necessary for successful results when learning this technique. PMID- 8363424 TI - [Cardiorespiratory and metabolic changes during prolonged exercise at 50% of the maximal load. Application to rehabilitation of severe cardiac insufficiencies]. AB - The object of physical training in patients with chronic cardiac failure and severe left ventricular dysfunction is to improve skeletal muscle adaptation without impairing myocardial function. It is acknowledged that aerobic exercise limits increased ventricular strain. Therefore, the authors decided to determine whether exercise at 50% maximal power load constituted aerobic training. Eight patients with chronic cardiac failure (age 57 +/- 10 years; resting radionuclide ejection fraction: 25 +/- 5%) performed a rectangular submaximal exercise for 20 minutes at 50% of maximal aerobic load (MAL) as determined by a prior triangular exercise test at 10 W/mn (MAL = 92 +/- 26 Watts-Peak VO2 = 14.8 +/- 2.4 ml/Kg/mn). Gaseous exchanges (VO2, VCO2) minute volume (MV) and serum lactates were measured at rest and every 5 minutes during exercise. MV, VO2 and VCO2 increased significantly (p < 0.005) with a change of less than 5% between the 20th and 10th minute. Respiratory quotient was unchanged until the end of exercise and serum lactate levels stabilised between the 10th (3.4 +/- 0.66 mmol/l) and the 20th minute of exercise (3.5 +/- 0.47 mmol/l). No significant relationship was observed between ventilation and serum lactate or between respiratory quotient and serum lactate. These results confirm that exercise at 50% of maximal load is aerobic training even in patients with severe left ventricular dysfunction. This parameter would appear to be more useful than using the heart rate which is often abnormal in chronic cardiac failure (abnormal chronotropic response, atrial or ventricular arrhythmias). PMID- 8363425 TI - [Prognosis after aortic valve replacement for aortic valve stenosis with or without associated coronary lesions]. AB - With the increasing age of patients and the progression of degenerative pathologies, the management of aortic stenosis (AS) with coronary artery disease is becoming more frequent. Reported results of combined valve and coronary surgery are equivocal especially with respect to the increased risk compared with aortic valve replacement without coronary surgery. The authors assessed the results of combined surgery by comparing two groups of patients with AS operated between 1979 and 1991: 122 patients with coronary lesions undergoing combined valve and coronary surgery (Group I) and 122 patients without coronary artery disease undergoing isolated aortic valve replacement (Group II) and paired with Group I patients for 5 prognostic factors (age, sex, functional status, date of surgery and left ventricular ejection fraction). Pairing the patients provided comparable populations for these 5 factors. The average age was high (68 years in Group I with over 50% of patients over 70 years of age) and most patients were in functional classes III or IV (67% in Group I). In Group I, 67% of patients had multivessel disease (average 2 vessel disease). Aortic valve replacement was associated with an average of 1.7 coronary bypass grafts per patient. Myocardial protection was the same in all cases using cold potassium enriched cardioplegic solutions. Operative mortality was 10.6% in Group I compared with 4.9% in Group II (NS) and the respective perioperative infarction rates were 6.6% and 0.8% (p < 0.02). Seven year actuarial survival rates were 71.8% in Group I and 74.9% in Group II (NS) without any increased late mortality in Group II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363426 TI - [Lipomatous hypertrophy of the interatrial septum. Apropos of 3 cases and review of the literature]. AB - Lipomatous hypertrophy of the interatrial septum is characterised by an accumulation of fatty tissue in the interatrial septum. The authors report three cases, one presenting with sinus tachycardia and the other two being chance findings. Echocardiography associated with cardiac computerised tomography or magnetic resonance imaging usually confirms the diagnosis. In half the cases, supraventricular arrhythmias and suggestive P wave abnormalities are observed on the electrocardiogram. The diagnostic value of transoesophageal echocardiography is emphasised; it demonstrates the massive forms which may obstruct flow from the superior vena cava into the right atrium. The authors observe a discrepancy between the prevalence of this condition in autopsy series (about 1%) and the small number of cases described at echocardiography, suggesting that the diagnosis is probably missed. PMID- 8363427 TI - [Quantitative evaluation of the cardiovascular risk associated with hormone substitution therapy during menopause]. AB - The cardiovascular risk of postmenopausal hormone replacement therapy is a controversial subject. A quantitative evaluation of 12 studies of cohorts show a global relative risk of major ischemic cardiac disease of 0.69 (95% confidence interval: 0.60-0.79) in women having or having had oestrogen therapy compared with women who have never taken this treatment. This relative risk was 0.94 (95% confidence interval: 0.77 to 1.15) for stroke and 0.80 (95% confidence interval: 0.65-0.97) for cardiovascular mortality. These results are coherent with the hypothesis of a protective effect of oestrogens against coronary artery disease in postmenopausal women. However, they cannot be generalised to hormone replacement therapy usually proposed in France. The influence of an association of oestrogen-progesterone therapy and the effects of administering oestrogens by an extra-gastrointestinal route on vascular risk are unknown. Randomised clinical trials are needed to determine the effects of postmenopausal hormone replacement therapy on athero-thrombotic disease. PMID- 8363428 TI - [Spontaneous coronary artery dissection: apropos of a case with associated spasm and regression of the dissection]. AB - The authors report the case of a 34 year old woman with postpartum myocardial infarction due to spontaneous coronary dissection of the distal circumflex artery. A spontaneously regressive spasm of the right coronary artery was also observed. The outcome with heparin, glyceryl trinitrate and calcium antagonist therapy was favourable. Over one year later, coronary angiography showed total resolution of the dissection and a large aneurysm of the inferior and septal walls of the left ventricle. This case is an example of post-partum spontaneous coronary dissection, in a particular vascular context. There are, however, other causes of spontaneous coronary artery dissection (atherosclerosis, eosinophilic syndrome...). Spasm may aggravate the consequences of coronary artery dissection and cause worse myocardial damage. The medical treatment, especially with regards to thrombolytic therapy, requires further codification. PMID- 8363429 TI - [Primary aspergillus endocarditis]. AB - A 38-year old man was admitted for investigation of suspected endocarditis presenting with two cerebrovascular accidents and pyrexia. The initial clinical, echocardiographic and infectious investigations were normal, apart from a neutrophilic leukocytosis. The clinical course was marked by the recurrence of systemic embolism in the lower limbs, the appearance of cervical and axillary lymphadenopathy and, within a short period of time, of massive aortic valve vegetations. The diagnosis of aspergillosis was made from the culture of a peripheral embolus recovered by a Fogarty catheter and this was confirmed by the positivity of serological investigations. The patient died within two months despite antifungal therapy. Aspergillus endocarditis is characterised by its rapid progression, the volume and embolic tendency of the vegetations, the relative inefficacy of medical therapy and the potential benefits of early surgical management. PMID- 8363431 TI - [Airborne Japanese red cedar allergens studied by the immunoblotting technique- comparison with pollen counts obtained by Durham sampling and effect of weather]. AB - We collected airborne particles with Burkard's sampling tape in Toyama from March to July. According to the immunoblotting technique (Takahashi et al, 1990), the airborne pollen allergens were reacted with anti-Cry j I polyclonal antibody and were stained as blue spots. The areas of these spots were measured with a color image analyzer (CIA) and a densitometer. There were significant correlations between the airborne Cry j I allergen spots (CIA and densitometer) and the pollen counts obtained with a Durham sampler (r = 0.624, 0.555, p < 0.001). The airborne Cry j I allergens however, tended to maintain a higher level than the pollen counts (Durham) in May. We theorized that this discrepancy is caused by cross reactivity with other pollen or crushed cedar pollen particles have allergenicity. There was a negative correlation between the Cry j I spots and rainfall. The pollen counts had a negative correlation with rainfall, and a positive correlation with average wind speed. These results suggest that this method is useful in evaluating fluctuations in airborne Cry j I allergen. PMID- 8363430 TI - [Diffuse cholesterol embolism after fibrinolysis for myocardial infarction]. AB - The authors report the case of a 57 year old man admitted to hospital 3 hours after the onset of an infero-latero-basal infarct who underwent thrombolytic therapy with intravenous streptokinase, in whom the immediate outcome was complicated by multiple cholesterol embolisation which cause renal failure, mesenteric ischemia, medullary ischemia and livedo reticulosis of the lower half of the body complicated by gangrene of the toes, despite the fact that cardiac catheterisation had not been performed. This case (fifth reported case) of multiple cholesterol embolisation from the abdominal aorta caused by thrombolysis is the earliest presentation of this complication in the literature. PMID- 8363432 TI - [Changes in antigen-specific IgG, IgG4, and IgE antibodies in patients receiving immunotherapy with house-dust extract]. AB - We measured allergen-specific IgG, IgG4, IgE antibodies and total IgE in sera from 64 patients who were receiving conventional immunotherapy (IT) with house dust (HD) extract. The sera were taken before and after IT. To measure allergen specific antibodies, we used crude DF antigen, Der f I and Der f II for IgG and IgG4 antibodies, and crude DF antigen for IgE antibodies. The patients were divided into 3 groups: very short term group (IT period < 2 years, n = 9); short term group (2 < = IT period < 7 years, n = 25); long term group (7 years < = IT period, n = 30). The specific IgG antibodies for DF crude antigen did not change in any group. The specific IgG antibodies for Der f I and Der f II increased in the short term group and in the long term group. The specific IgG4 antibodies for all three antigens increased remarkably in the short term group and in the long term group. In the very short term group, however, the specific IgG4 antibodies did not increase for any antigen. Total IgE and the specific IgG antibodies did not change through IT. The specific IgG4 antibodies increased significantly through IT, but the time course of the increment of the IgG4 antibodies was not parallel with the clinical course of IT. PMID- 8363433 TI - [Lymphocyte subpopulation in asthmatic children with chronic bronchial obstruction]. AB - Lymphocyte subpopulations in peripheral blood were examined in asthmatic children, using fluorescent monoclonal antibodies. The patients were divided into three groups: Group I, no attack (FEV1.0% > or = 80% group), Group II, no attack (FEV1.0% < 80% group) and Group III, asthmatic attack group. The percentage of CD3HLADR/CD3 in the Group II and Group III were 5.58 +/- 3.59 and 5.44 +/- 4.34, respectively, which were significantly higher than that in the Group I subjects (2.70 +/- 2.17). This finding suggests that the patients with long lasting bronchial obstruction may have chronic inflammation in the airway even in the remission stage of asthmatic attacks. PMID- 8363434 TI - [The influence of indoor environmental factors on the onset of allergic disease]. AB - To predict and prevent the onset of allergic diseases, we studied the effects of indoor environmental factors, such as diet, on pregnant women and carried out follow-up studies on their infants. Blood samples were collected at random from women who were diagnosed as pregnant (n = 2045). Umbilical cord blood was collected at delivery (n = 1453). To evaluate the efficacy of food guidance, the pregnant women were divided into two groups--one receiving simple diet guidance starting in the later stages of pregnancy, and one receiving no guidance whatsoever. A follow-up survey on allergic symptoms was done on their two-year old infants, revealing a lower incidence of symptomatic manifestations in the diet guidance group (p < 0.001). Respiratory symptoms (p < 0.05) were associated with maternal smoking and outside work during pregnancy. A study on food guidance in combination with environmental factors revealed that the incidence of respiratory symptoms in two-year-old infants whose mothers received diet guidance in a good indoor environment was held down to around 36.1%, while the incidence in infants whose mothers received diet guidance in a poor indoor environment was 48.1%. PMID- 8363435 TI - [Evaluation of the relationship between immediate hypersensitivity and environmental factors by intracutaneous skin tests and specific IgE antibodies in allergic children. Part 2. The age distribution of immediate hypersensitivity by intracutaneous skin test and radioallergosorbent test]. AB - To evaluate immediate hypersensitivity and environmental factors, 2,187 allergic children were given intradermal skin tests (ID test) and specific IgE antibodies (RAST) at Kudanzaka Hospital for 21 years (1967-1987). The incidence of positive ID test to house dust (HD) was 23% at 1 year, 50% at 2 years, 63% at 3 years and 84% at 8 years of age. The results of average positive test obtained at an earlier age in 1975 and 1985 than in 1965. Children born recently begin to have positive test scores earlier than those born between 1965 and 1969. This could be related to the recent increase in the number of HD mites. The incidence of positive ID test to Japanese cedar pollen (sugi) was 5% at 1 year, 10% at 4 years, 16% at 8 years and 30% at 15 years of age. The positive test scores were again obtained at an earlier age in 1975 and 1985 than in 1965, in the same way as for HD mites. Children born between 1965 and 1969 showed 30-60% positive rate after 13 years of age; this level was seen after 10 years of age in children born in 1975 and 1979, and after 6 years in those born between 1980-1984. This could be due to the recent increase in the amount of sugi pollen. Only Candida showed any significant rises in positive rate 27% at 1 year of age; slow increase was observed in the case of ragweed, molds, epidermals and others. No remarkable change was seen in ragweed and Alternaria at the years of examination and the years of birth. PMID- 8363437 TI - [Evaluation of the Magic Lite SQ specific IgE kit]. AB - The new IgE specific antibody assay kit (Magic Lite SQ) was evaluated by comparing its results with those obtained by the Phadebas RAST and the skin prick tests. Sera from allergic children were used in the tests. The correlation coefficients between the Magic Lite SQ and the Phadebas RAST were as follows: 0.87 for D.p., 0.89 for D.f., 0.87 for HD1, 0.55 for HD2, 0.76 for orchard grass, 0.93 for cat dander, 0.78 for Alternaria, 0.88 for egg white, 0.75 for egg york, 0.81 for milk, 0.75 for say bean, and 0.60 for shrimp. The concordance rate of the two methods was high, except on the case of HD2. The sensitivity and specificity of Magic Lite SQ to the skin prick test was high, except on the case of HD2 and orchard grass. Dilution tests using samples from D.f. positive patients showed a good linearity and excellent quantitativeness. When mite allergen was added to D.f. positive pool serum, mite specific IgE antibody yielded an excellent inhibition curve of up to a maximum of 96%. Since the Magic Lite SQ requires only a small sample of serum and can completed the test in a short time, it is a useful and specific IgE antibody assay kit. PMID- 8363436 TI - [Improvement of intractable nocturnal asthma treated by therapeutic awakening]. AB - A 33-year-old female was admitted to our hospital because of intractable asthma which had not been improved by intensive treatment at another hospital. Her asthmatic attacks were improved within a week by treatments including systemic corticosteroids and mechanical ventilation. However, in a few weeks nocturnal asthma recurred frequently, and it was resistant to various bronchodilators and steroids. Therapeutic awakening, that is, awakening the patient quietly at 3 a.m. with inhalation of 2.5 mg salbutamol was started. Her symptoms and physical findings rapidly improved thereafter. It was concluded that therapeutic awakening may be effective for the treatment of refractory morning dipping of asthma. PMID- 8363438 TI - [Detection of antibody specific to rifampicin metabolite by ELISA--mechanism of sensitization by rifampicin]. AB - A 46-year-old male tuberculosis patient developed acute renal failure and liver dysfunction following the oral administration of rifampicin (RFP). The mechanism of the reaction was examined by means of enzyme-linked immunosorbent assay (ELISA). 3-formylrifamycin-SV (Formylrifamycin), which is one of RFP metabolites, was conjugated to human serum albumin. ELISA was performed with this conjugate (Formylrifamycin-HSA) as an antigen. We also evaluated 100 tuberculosis patients receiving oral RFP and 45 healthy volunteers in order to determine the incidence of sensitization by RFP. IgG and IgM antibodies specific to Formylrifamycin-HSA were detected in serum from the patient with RFP-induced renal failure. Among the IgG subclasses, IgG1 antibody was detected. IgG and IgG1 antibodies specific to Formylrifamycin-HSA were detected in serum from only one of the 100 tuberculosis patients. Our results indicate that sensitization to RFP can occur on oral administration, and that acute renal failure was caused by IgG, IgM, and IgG1 antibodies specific to Formylrifamycin as a hapten. PMID- 8363439 TI - [Influence of airway temperature and humidity of hyperventilation induced bronchoconstriction in rabbits]. AB - It has been suggested that humidity and temperature of inspired air is important in determining the severity of hyperventilation induced bronchoconstriction (HIB). To investigate whether water loss or heat loss from airway plays more important role to induce HIB, we compared the effect of temperature and humidity of inspired air on HIB, in sensitized and non-sensitized rabbits. Inspired air containing 5% CO2 was conditioned to dry or humidified and to temperature of 9 degrees C or 25 degrees C during isocapnic hyperventilation. In sensitized rabbits, marked bronchoconstriction was observed when inspired air dry regardless of temperature. We conclude that 1) HIB is produced in sensitized rabbits and 2) humidity rather than temperature of inspired air is more important to induce HIB. PMID- 8363440 TI - [A method for the quantification of interleukin-4 in serum (sandwich ELISA) and IL-4 levels in patients with atopic dermatitis]. AB - We have developed a sandwich enzyme-linked immunosorbent assay (ELISA) using chemiluminescent enzyme substrate AMPPD for the quantification of interleukin 4 (IL-4) in serum. IL-4 in serum could be measured in concentrations from 0.17 pg/ml. The IL-4 levels in patients with atopic dermatitis were significantly higher than those in normal controls. PMID- 8363441 TI - Landau-Kleffner syndrome: some suggestions. PMID- 8363442 TI - Poor tolerability of MK-458. PMID- 8363443 TI - Cognition in relation to magnetic resonance imaging in head-injured children and adolescents. AB - To investigate the relationship between cognitive sequelae and magnetic resonance imaging (MRI) findings following closed head injury of varying severity in the pediatric age range, 76 head-injured children and adolescents were studied at least 3 months after trauma and compared with 57 normal controls. Problem solving, planning, verbal and design fluency, memory, and response modulation were assessed. Significant effects of injury were obtained on all of the cognitive measures. Cognitive impairment was more consistently present on the various outcome measures in children who were 6 to 10 years old at the time of the study than in the older children and adolescents. Magnetic resonance imaging disclosed areas of abnormal signal in the frontal lobes of 42 patients, whereas focal lesions restricted to the extrafrontal region were found in 15 children. Regression analyses disclosed that taking into account the size of frontal lobe lesion enhanced the relationship between cognitive performance and the severity of injury. PMID- 8363444 TI - Long-term survival of veterans with traumatic spinal cord injury. AB - OBJECTIVE: To investigate the long-term survival of veterans with traumatic spinal cord injury (SCI). DESIGN: Survival in a retrospective inception cohort of veterans suffering service-connected traumatic SCI is compared with survival among veterans disabled by other conditions, survival among nondisabled veterans, and a population-based life table. SETTING: Subjects were identified from a national census of veterans with service-connected disabilities, using a selection algorithm based on disability codes. PATIENTS: A retrospective cohort of 5545 male veterans with traumatic SCI, surviving at least 3 months after injury, is compared with a stratified random sample of 7077 disabled veterans without SCI, a stratified random sample of 6967 nondisabled veterans, and a life table formed from similarly aged American males. MAIN OUTCOME MEASURE: Survival curves, extending from 3 months to 40 years after injury. RESULTS: The mean life expectancy of veterans suffering traumatic SCI and surviving at least 3 months is an additional 39 years after injury, 85% that of similarly aged American males. Although survival with traumatic SCI was comparable to that of the disabled control subjects for approximately 20 years after onset, a clear deficit occurred beyond this point. Older age at injury is a stronger predictor of poorer long term survival than is complete quadriplegia. CONCLUSIONS: Among patients who survive the acute phase of their traumatic SCI, long-term survival is relatively good. Health care planners, providers, and communities should anticipate an increasing number of persons aging with SCI. PMID- 8363445 TI - Cerebral abnormalities in myotonic dystrophy. Cerebral blood flow, magnetic resonance imaging, and neuropsychological tests. AB - OBJECTIVE: To study cerebral abnormalities in myotonic dystrophy (MD) and determine the different patterns of cerebral function in patients with MD with maternal (mMD) vs paternal (pMD) inheritance. DESIGN: Patients with MD and normal controls were studied with neuropsychological testing, magnetic resonance imaging, and single photon emission computed tomography. SETTING: Studies were done at Harbor-UCLA Medical Center, Torrance, Calif. PATIENTS AND OTHER PARTICIPANTS: Twenty-two consecutive-patients with MD, 11 of whom had pMD and eight mMD, and 10 normal controls were studied. Diagnoses were made on the basis of family history, electromyography, and clinical examinations. Normal subjects in the same age distribution were studied for comparisons. RESULTS: We found significantly lower neuropsychological performance and cerebral blood flow in the patients with MD compared with the controls. Patients with mMD had statistically lower scores on IQ tests and more extensive cerebral hypoperfusion when compared with those with pMD. Changes in cerebral blood flow were most severe in the frontal and temporoparietal association cortex. Cerebral blood blow measures strongly correlated with IQ. CONCLUSIONS: Patients with mMD had earlier onset of disease and lower IQs than the pMD group. The pattern of cerebral perfusion in the mMD group was consistent with a diffuse brain injury, while cerebral perfusion in pMD showed more minor changes. These findings emphasize the cognitive differences between mMD and pMD. PMID- 8363446 TI - Idiopathic granulomatous angiitis of the central nervous system. Diagnostic challenges. AB - OBJECTIVE: Granulomatous angiitis of the central nervous system (CNS) is a rare cause of vasculitis involving the brain and spinal cord and is included in lists of disorders causing strokes. To determine the frequency of strokes (eg, sudden onset of focal symptoms) as a presenting complication and to determine the sensitivity of angiography and other technologies in detecting vasculitis in histologically proved cases of idiopathic granulomatous angiitis of the CNS (IGANS), we reviewed the published literature. DATA SOURCES: A biopsy-proved case of IGANS in a patient presenting without strokes and with a normal angiogram is reported. Additional cases of pathologically proved IGANS where results of angiography or other neuroimaging procedures were available were found by search of MEDLINE and bibliographies of pertinent articles and books. DATA EXTRACTION: We compared our case with 39 reported cases of histologically proved granulomatous angiitis of the CNS not associated with Hodgkin's disease, herpes zoster, sarcoidosis, or other proximate cause. We included only those cases that had been evaluated with angiography or other neuroimaging techniques before death or biopsy. DATA SYNTHESIS: Analysis of these cases shows that strokes as presenting complications are rare in IGANS. Most patients present with a diffuse encephalopathy and, when focal symptoms develop, they tend to develop gradually. Including our case, 56% of 41 angiograms performed in 31 reported patients with histologically proved IGANS were abnormal, but only 27% were diagnostic for vasculitis. CONCLUSIONS: We conclude that stroke is uncommon as a presenting complaint in IGANS and angiography is insensitive as a screening test for these patients. PMID- 8363447 TI - Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer's disease. AB - A retrospective chart review of clinical symptoms was done for 20 consecutive patients in whom postmortem examination had revealed senile plaques and neurofibrillary tangles in a distribution consistent with Alzheimer's disease. All patients had met clinical diagnostic criteria for probable Alzheimer's disease. On initial examination, 1 to 14 years beyond putative onset of the dementia, all patients displayed at least some memory impairment. In 16 patients, disturbances of attention or recent memory were among the most salient features. In two patients, language disturbances, and in two others, visuospatial deficits, were more prominent than difficulties with memory and attention. On initial examination, 17 of the 20 patients displayed word-finding difficulties, characteristically in the context of a fluent, anomic aphasia. All of the 12 reexamined patients demonstrated progressive, although variable, deterioration. In general, the initial salient deficit remained salient during much of the disease course. Language comprehension was spared in the earlier stages but eventually deteriorated. Severe deficits emerged in all major cognitive domains as the disease reached the terminal stages. Nonfluent aphasias (eg, Broca's aphasia) were not observed even in the advanced stages of the disease. PMID- 8363448 TI - Amygdala atrophy in Alzheimer's disease. An in vivo magnetic resonance imaging study. AB - OBJECTIVES: To study the ability of magnetic resonance imaging to measure the volume of the amygdala and detect amygdala atrophy in patients with early Alzheimer's disease. DESIGN: Prospective case-control study and "blind" measurements. SETTING: Subjects were ambulatory outpatients selected from an institutional practice in Paris, France. PATIENTS: We studied 11 patients with probable Alzheimer's disease according to National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) inclusion and exclusion criteria, as well as six age-matched control subjects. INTERVENTION: None. MAIN OUTCOME MEASURE: A 1.5-T magnetic resonance imager was used to acquire the images. Two neuroradiologists independently and blindly measured the volume of the right and left amygdalas on high-resolution contiguous slices. In addition, other cerebral structures, ie, the sylvian fissures, temporal lobes, lateral and third ventricles, corpus callosum, and hippocampal formation, were measured on a single slice. RESULTS: The values obtained by the two observers correlated highly (r = .90), and interrater variability was 13%. The Alzheimer's disease group showed significant (33%, P < .0001) atrophy of the amygdala when compared with the control group. The other structures showed less variation. CONCLUSION: Significant amygdala atrophy can be detected in vivo in patients with early Alzheimer's disease by means of standard magnetic resonance imaging. This technique may be useful in the early diagnosis of Alzheimer's disease. PMID- 8363449 TI - Temporal lobe regions on magnetic resonance imaging identify patients with early Alzheimer's disease. AB - OBJECTIVE: The goal of the study was to examine the volume of selected brain regions in a group of mildly impaired patients with Alzheimer's disease (AD). Five regions were selected for analysis, all of which have been reported to show substantial change in the majority of patients with AD at some time in the course of disease. DESIGN: Case-control study with the experimenter "blinded." SETTING: Hospital-based magnetic resonance imaging center. PARTICIPANTS: Fifteen subjects, eight patients with the diagnosis of probable dementia of the Alzheimer type made in concordance with National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria and seven age-matched healthy control subjects. RESULTS: Three of the volumetric measures were significantly different between patients with AD and controls: the hippocampus, the temporal horn of the lateral ventricles, and the temporal lobe. Two of the measures did not significantly differentiate patients with AD and controls: the amygdala and the basal forebrain. A discriminant function analysis demonstrated that a linear combination of the volumes of the hippocampus and the temporal horn of the lateral ventricles differentiated 100% of the patients and controls from one another. CONCLUSIONS: The results suggest that the hippocampus and the temporal horn of the lateral ventricles may be useful as antemortem markers of AD in mildly impaired patients. PMID- 8363450 TI - Cerebral glucose metabolism as a predictor of recovery from aphasia in ischemic stroke. AB - OBJECTIVE: The recovery of language function seen in poststroke aphasia is significantly related to the severity of the initial neurologic deficit. However, a great deal of variability still remains in the improvement that is actually achieved. To detect predictors that will help in explaining this variability, positron emission tomography (PET) and fluorodeoxyglucose F 18 (18-F fluorodeoxyglucose) were used and the results were analyzed by stepwise regression. DESIGN: Using PET imaging after injection of fluorodeoxyglucose F 18, the regional changes in glucose metabolism in 26 patients at a period of 12 to 18 days following an ischemic stroke involving the left middle cerebral artery were examined. A second PET examination was performed on 17 of our 26 patients who were able to perform speech activation exercises. All patients received an initial and a 4-month follow-up evaluation of language performance. SETTING: During the two PET studies and the first language assessment, the patients were hospitalized in a neurologic clinic. The follow-up evaluation of language performance was performed when the patients were ambulatory. PATIENTS: Twenty-six patients (10 women, 16 men; aged 38 to 77 years; mean +/- SD, 60 +/- 9.2 years) were selected in the study. Their aphasias were of various types and of varying severity ranging from mild impairment to severe global aphasia. MAIN OUTCOME MEASURES: For the stepwise regression analysis of variables, the following variables were analyzed in resting and activation PET to explain residual variance from the first to the second Token Test: regional cerebral metabolic rate for glucose of infarct and mirror region, left and right cerebral and cerebellar hemispheres, left and right Broca's area, left and right Wernicke's area, and left and right temporoparietal cortex. RESULTS: As was expected, early and late Token Tests exhibit a high correlation (.85). The stepwise regression analysis shows that only the left cerebral hemisphere glucose value of the resting PET had significant effect on the residual variance of the Token Test regression. Regional metabolic rates during speech activation had the largest contribution to a significant recovery from aphasia. The infarct area and its corresponding mirror region, the left Broca's area, and the entire left cerebral hemisphere accounted for 80% of the residual variance. CONCLUSIONS: These results emphasize not only the application of PET activation studies in the prediction of a tissue's potential reserve capacity but also the importance of left hemisphere integrity in the recovery of functional language. PMID- 8363451 TI - Hippocampal atrophy in normal aging. An association with recent memory impairment. AB - OBJECTIVE: To estimate the prevalence of radiographically detectable hippocampal atrophy (HA) in a normal aging sample and to test whether such atrophy is associated with memory dysfunction. DESIGN: One hundred fifty-four medically healthy and cognitively normal elderly persons (aged 55 to 88 years) received magnetic resonance imaging and/or computed tomographic scans designed to identify HA. One hundred forty-five of these subjects also underwent psychometric tests of memory function. Multivariate analyses of variance were used to evaluate differences in memory performance between subjects with and without HA. SETTING: This study was conducted at a research clinic for the investigation of age associated neuropsychological and neuroradiologic changes. PARTICIPANTS: Based on the following criteria, 154 subjects were consecutively selected from a larger group of elderly research volunteers participating in a study of normal aging: age of 55 years or greater; Global Deterioration Scale score of 2 or less; and Mini-Mental State examination score of 28 or greater. Subjects with evidence for significant medical, psychiatric, or neurologic disease were excluded. MAIN OUTCOME MEASURES: Outcome measurements included individual psychometric test scores and computed tomographic-magnetic resonance imaging hippocampal atrophy ratings. RESULTS: Nearly 33% of the subjects had radiographic evidence for HA. The prevalence of HA increased significantly with age and was more common in male than female subjects. After controlling for age, level of education, and vocabulary, subjects with HA were found to perform more poorly on tests of recent (secondary) verbal memory when compared with subjects without HA (P < .01). No significant differences were found for tests of immediate (primary) memory. CONCLUSION: We conclude that HA is a common accompaniment of normal aging and is associated with mild memory impairment. Additional research is needed to determine whether HA constitutes a significant risk for future dementia. PMID- 8363452 TI - Ophthalmologic manifestations in MELAS syndrome. AB - We describe a 15-year-old boy with full-blown mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and chronic progressive external ophthalmoplegia (CPEO). He presented with visual disturbance, hearing impairment, continuous partial epilepsy on the right aspect of the face, and right hemiparesis since the age of 13. Four months later, he experienced another strokelike episode with continuous partial epilepsy on the left hand. Serial computed tomographic scans revealed bilateral parieto-occipital hypodense lesions with gyral enhancement and an additional low-density lesion in the right frontal area 4 months later, respectively. Results of laboratory examinations disclosed lactic acidosis and mitochondrial myopathy with many ragged-red fibers. To identify the defective gene in mitochondrial DNA, a simple molecular test was performed by using restriction endonuclease Apa I. A transition from A to G was found at nucleotide position 3243 of the tRNA(Leu) gene. Interestingly, the patient also had marked external ophthalmoplegia and ptosis commonly found in patients with CPEO. Therefore, we suggest that ophthalmoplegia also occurs in the MELAS syndrome. PMID- 8363454 TI - Updating Keratospeak IV. PMID- 8363453 TI - Visual evoked potential characteristics and early diagnosis of Pelizaeus Merzbacher disease. AB - OBJECTIVE: Early diagnosis of Pelizaeus-Merzbacher disease; assessment of disease progression. DESIGN: Pediatric neuro-ophthalmology evaluation of visual function with pattern and luminance visual evoked potentials; behavioral state assessment; electrophysiological diagnostic test; baseline estimates at the age of 11 weeks; 1-year follow-up. SETTING: University hospital electrodiagnostic vision research laboratory. PATIENTS: CASE STUDY: X-linked Pelizaeus-Merzbacher disease; leukodystrophy; patient tested at the age of 11 weeks and at the age of 58 weeks for follow-up; five age-matched normal controls. INTERVENTIONS: Physical therapy, medication, evaluation. MAIN OUTCOME: Early diagnosis; diagnostic confirmation; objective monitor of disease progression. RESULTS: Abnormal spatial and temporal vision and abnormal visual pathway maturation; visual evoked potentials of proband with Pelizaeus-Merzbacher disease were grossly abnormal, reflecting myelination disorder. CONCLUSIONS: Visual evoked potential pediatric electrodiagnosis yields reliable measures of visual function and visual system maturation in leukodystrophy. PMID- 8363455 TI - Fixation of conjunctival autografts with an organic tissue adhesive. PMID- 8363456 TI - Predictive factors for endothelial cell loss after penetrating keratoplasty. PMID- 8363458 TI - Branhamella (Moraxella) catarrhalis endophthalmitis. PMID- 8363457 TI - Posttraumatic endophthalmitis caused by Lactobacillus. PMID- 8363459 TI - Streptococcus pneumoniae endophthalmitis following strabismus surgery. PMID- 8363460 TI - A diagnostic dilemma: one foreign body or two? PMID- 8363461 TI - Glaucoma and the law. Cox v District of Columbia. PMID- 8363462 TI - Looking behind the eyes. The proper use of modern imaging. PMID- 8363463 TI - Advising patients about age-related macular degeneration. PMID- 8363464 TI - 0.3% ciprofloxacin ophthalmic ointment in the treatment of bacterial keratitis. The Ciprofloxacin Ointment/Bacterial Keratitis Study Group. AB - OBJECTIVE: To determine the efficacy and safety of topical 0.3% ciprofloxacin hydrochloride ophthalmic ointment in the treatment of bacterial keratitis. DESIGN: Prospective case series with a nonrandomized comparison of culture positive, evaluable cases (ciprofloxacin ointment group) with culture-positive, concurrent patients (nonenrolled group) treated with conventional therapy. SETTING: Multicenter clinical study. PATIENTS: After informed consent was obtained, 253 eligible patients underwent corneal scrapings and received topical ciprofloxacin ointment; 145 (57%) had positive cultures and completed the follow up schedule. Forty (70%) of 57 apparently eligible patients had culture-positive bacterial keratitis but were not enrolled in the ciprofloxacin ointment study during the same period. INTERVENTION: Ciprofloxacin ophthalmic ointment instilled every 1 to 2 hours for 2 days, then every 4 hours for 12 days. MAIN OUTCOME MEASURES: Clinical evaluation of signs at 1, 3, 7, and 14 days of treatment and the overall condition classified as clinical success (cured or improved) or failure (unchanged or worse) during and after therapy. RESULTS: Clinical success with the initial treatment occurred in 135 patients (93%) in the ciprofloxacin ointment group and in 28 patients (70%) in the nonenrolled group. Of the 10 ciprofloxacin clinical failures, seven were staphylococcal; two, pneumococcal; and one, polybacterial. The 90% minimum inhibitory concentration of ciprofloxacin was 3 mg/L or less for corneal bacterial isolates. No serious adverse event attributable to ciprofloxacin ointment occurred, although 32 (13%) of 253 patients developed a transient white crystalline corneal precipitate shown with liquid chromatography in two cases to be ciprofloxacin. CONCLUSION: Ciprofloxacin ophthalmic ointment is an effective and safe topical antimicrobial agent for the treatment of bacterial keratitis caused by susceptible microorganisms. PMID- 8363465 TI - Optic nerve sheath decompression for glaucomatous optic neuropathy with normal intraocular pressure. AB - OBJECTIVE: To report our therapeutic experience with optic nerve sheath decompression in patients with normal-pressure glaucoma. DESIGN: A case series of seven eyes from six patients with glaucoma and normal intraocular pressures who continued to have progressive visual field loss despite conventional therapy. SETTING: A hospital-based, referral glaucoma service. PATIENTS: Three men (67, 67, and 72 years of age) and three women (58, 61, and 70 years of age). INTERVENTIONS: Optic nerve sheath decompression. MAIN OUTCOME MEASURES: Visual field data and visual acuity measurements were obtained at regular intervals during the postoperative periods (range, 3 to 18 months). RESULTS: Two of seven eyes from six patients appear to have enjoyed an initial significant improvement in their visual fields with improved visual acuity in one eye of one patient. The visual fields, however, appear to have deteriorated 18 months after the initial procedure in these two patients. In the remaining four patients, no further improvement or deterioration was observed within a limited follow-up period. CONCLUSIONS: The transient improvement in the visual fields of one eye from each of two patients documents an initial successful use of optic nerve sheath decompression in patients with nerve fiber bundle damage in the absence of optic nerve head swelling. However, the long-term potential of optic nerve sheath decompression in these patients may be of limited value. PMID- 8363466 TI - Central serous chorioretinopathy in endogenous hypercortisolism. AB - OBJECTIVE: To examine the potential association of central serous chorioretinopathy with endogenous hypercortisolism (Cushing's syndrome). DESIGN: Ophthalmologic survey of consecutively admitted patients with endogenous Cushing's syndrome. SETTING: An eye clinic of a research center (National Eye Institute, Bethesda, Md). PATIENTS: Sixty consecutive patients with confirmed endogenous Cushing's syndrome. MAIN OUTCOME MEASURES: Findings from complete ophthalmologic evaluation. RESULTS: Three (5%) of 60 patients had one or more episodes of appropriately documented central serous chorioretinopathy. In all cases, the episodes occurred during the period of hypercortisolism. CONCLUSIONS: Central serous chorioretinopathy is an uncommon manifestation of endogenous Cushing's syndrome. Since central serous chorioretinopathy has been associated with other hypercortisolemic states, we suggest that glucocorticoids may play a role in the development of this disease. PMID- 8363467 TI - Dual-perspective analysis of vascular formations in sickle cell retinopathy. AB - OBJECTIVE: To examine the sickle cell retina in dual perspective (vascular patterns en bloc and structure in serial sections) to gain new insights into sickle cell retinopathy. METHODS: We analyzed the retinas of two patients with sickle cell disease (a 54-year-old patient with hemoglobin SC, heterozygous for the S and C mutation in the beta chain of the globin gene, and a 20-month-old patient with sickle cell anemia [SS], homozygous for the S mutation) using the previously described adenosine diphosphatase flat-embedding technique. RESULTS: The dual-perspective analysis afforded by our technique revealed that the primary site of occlusions was located at the precapillary level. An unusual neovascular formation, the hairpin loop, was observed in both patients' retinas and appeared to result from recanalization of the wall of an occluded vessel. Many autoinfarcted pre-retinal neovascular formations were observed in the older SC patient. Two patent preretinal formations were studied in detail and their evolution appeared to be influenced by mechanical factors. The vessels appeared to have been extruded from the retina, perhaps owing to hydrostatic pressure secondary to downstream occlusions. Small pigmented lesions consisting of retinal pigment epithelial cells ensheathing channels that resembled autoinfarcted vessels were found in the eye of the SC patient. CONCLUSIONS: This study illustrates unusual morphological features of intraretinal and preretinal neovascularization and of chorioretinal lesions in sickle cell retinopathy and suggests alternative mechanisms for their formation. PMID- 8363468 TI - The Linxian cataract studies. Two nutrition intervention trials. AB - OBJECTIVE: To determine whether the vitamin/mineral supplements used in two cancer intervention trials affected the risk of developing age-related cataracts. DESIGN: Two randomized, double-masked trials with a duration of 5 to 6 years and end-of-trial eye examinations. SETTING: Rural communes in Linxian, China. PARTICIPANTS: In trial 1, 2141 participants aged 45 to 74 years, and, in trial 2, 3249 participants aged 45 to 74 years. INTERVENTIONS: Multivitamin/mineral supplement or matching placebo in trial 1; factorial design to test the effect of four different vitamin/mineral combinations in trial 2 (retinol/zinc, riboflavin/niacin, ascorbic acid/molybdenum, and selenium/alpha-tocopherol/beta carotene). MAIN OUTCOME MEASURES: Prevalence of nuclear, cortical, and posterior subcapsular cataracts in treatment groups at end of trials. RESULTS: In the first trial, there was a statistically significant 36% reduction in the prevalence of nuclear cataract for persons aged 65 to 74 years who received the supplements. In the second trial, the prevalence of nuclear cataract was significantly lower in persons receiving riboflavin/niacin compared with persons not receiving these vitamins. Again, persons in the oldest group, 65 to 74 years, benefited the most (44% reduction in prevalence). No treatment effect was noted for cortical cataract in either trial. Although the number of posterior subcapsular cataracts was very small, there was a statistically significant deleterious effect of treatment with riboflavin/niacin. CONCLUSIONS: Findings from the two trials suggest that vitamin/mineral supplements may decrease the risk of nuclear cataract. Additional research is needed in less nutritionally deprived populations before these findings can be translated into general nutritional recommendations. PMID- 8363469 TI - Ocular clinicopathologic study of the mitochondrial encephalomyopathy overlap syndromes. AB - Recent advances in molecular genetics have led to a better understanding of mitochondrially inherited diseases. Mitochondrial encephalomyopathy overlap syndrome is one such group of diseases in which ocular abnormalities are frequently manifest. The authors describe the clinical, molecular genetic, and pathologic findings of two patients with the mitochondrial encephalomyopathy overlap syndrome. The patients shared a similar clinical course with features overlapping the three traditionally distinct clinical phenotypes (the Kearns Sayre syndrome; the syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke [MELAS], and the syndrome of myoclonus, epilepsy, and ragged red fibers [MERRF]). The patients had identical mitochondrial DNA mutations (at nucleotide position 3243) and had similar ultrastructural abnormalities, including abundant enlarged mitochondria with "whorled" and "tubular" cristae. These abnormal mitochondria appeared to be preferentially distributed in cells with high metabolic activity (retinal pigment epithelium, corneal endothelium, and extraocular muscles). PMID- 8363470 TI - The prevalence of primary angle closure glaucoma and open angle glaucoma in Mamre, western Cape, South Africa. AB - OBJECTIVE: To determine the prevalence of primary angle closure glaucoma in the so-called Cape people of mixed ethnic background. DESIGN: A population-based prevalence study. SETTING: Mamre, a village near Cape Town, South Africa. PARTICIPANTS: Individuals aged 40 years or older. Historically, their ancestors were Southeast Asians and indigenous Africans and, to a lesser extent, Europeans. Of a total of 1194 people, 987 (82.7%) were examined. MAIN OUTCOME MEASURE: Primary angle closure glaucoma was diagnosed in individuals with previous acute or intermittent symptoms of angle closure and in individuals with an "occludable" angle and an intraocular pressure of greater than 21 mm Hg or a glaucomatous visual field. MAIN RESULTS: An age-related trend toward hypermetropia was found, which was greatest in women older than age 50 years. Gonioscopy identified Shaffer grade 1 angles in 89 (9%) of 987 subjects. The prevalence of primary angle closure glaucoma was 2.3% (23 subjects) and increased with age in both sexes. Women were affected more than four times as often as men and the sex difference persisted across all age groups. In comparison, the prevalence of primary open angle glaucoma was 1.5% (15 subjects). Primary glaucoma (angle closure plus open angle) was the leading cause of bilateral blindness in the community, with a prevalence rate of 0.5% (five subjects). CONCLUSIONS: This study identified primary angle closure glaucoma as a significant public health problem in the Western Cape Province. Because of the ethnic back-ground of the people studied, these findings may also apply to the populations of Southeast Asia. PMID- 8363471 TI - Indocyanine green angiography and ultrasonography of a varix of vortex vein. PMID- 8363473 TI - Problems with the design of observations and their statistical analysis. PMID- 8363472 TI - Whitnall's sling with superior tarsectomy for the correction of severe unilateral blepharoptosis. AB - The management of severe unilateral blepharoptosis is problematic. In the presence of poor levator function, conventional surgical techniques frequently do not adequately elevate a ptotic eyelid. From May 1988 through July 1991, we used 4- to 5-mm external resections of the superior tarsus in conjunction with a maximal aponeurectomy (Whitnall's sling procedure) to augment blepharoptosis correction in selected cases of severe unilateral blepharoptosis. Seventeen (68%) of 25 patients with poor levator function blepharoptosis who underwent this new surgical procedure achieved a lid height within 1 mm of the opposite lid with good or excellent ocular function, cosmesis, and eyelid crease formation. Mild to moderate degrees of exposure keratopathy developed early in the postoperative period in all patients. This exposure keratopathy ultimately resolved in most patients. Superior tarsectomy safely augments the blepharoptosis correction of a Whitnall sling procedure in severe blepharoptosis, improving the results of aponeurotic surgery in patients with severe unilateral blepharoptosis. PMID- 8363474 TI - Biliary injury at laparoscopic cholecystectomy: recognition and prevention. PMID- 8363475 TI - The case against open neck biopsy. AB - Many patients present with lateral neck lumps due to benign or malignant conditions, and they may be difficult to differentiate clinically. It is detrimental to perform an open neck biopsy on a patient with a cancer originating from the head and neck region (upper aerodigestive tract or skin) prior to definitive treatment. The biopsy interferes with the assessment and management of the neck, increasing morbidity. It may also decrease curability and perhaps induce fungation. A protocol to avoid the need for an open biopsy, using fine needle aspiration cytology and a thorough examination of the upper aerodigestive tract is recommended. The authors also recommend combined radical radiotherapy and surgery for the patient who has had an open biopsy. A thoughtless biopsy is both needless and harmful. PMID- 8363476 TI - Bile duct injury during laparoscopic cholecystectomy: a report of the Standards Sub-committee of the Victorian State Committee of the Royal Australasian College of Surgeons. AB - A survey of Victorian surgeons performing laparoscopic cholecystectomy was carried out. This report discusses the bile duct injuries identified in the survey. Twelve injuries were recorded, a rate of 0.2%. Three of the 12 required formal repair, the other 9 being treated by T-tube alone. Possible mechanisms of these injuries, the experience of the surgeon, the role of operative cholangiography and delays in recognition of the injury are discussed. PMID- 8363477 TI - Injuries to the bile duct resulting from laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has now become the treatment of choice for symptomatic gall stones. There does, however, appear to be an increased incidence of bile duct injuries. In this article, experience with eight patients who sustained a bile duct injury and were referred to the Hepatobiliary Service at Westmead Hospital, between 1990 and 1992, is reported. PMID- 8363478 TI - Percutaneous cystogastrostomy for treatment of pancreatic pseudocysts. AB - Cystogastrostomy or cystojejunostomy at open operation has been the usual treatment for symptomatic pancreatic pseudocyst. The aim of this study was to assess prospectively the results of percutaneous cystogastrostomy (PCG) for the treatment of symptomatic pseudocysts. The technique of PCG comprised initially of drainage of the pseudocyst with a 10 Fr percutaneous, transgastric catheter. This initial drainage catheter had two components; the first, between the pseudocyst and the stomach, drained the pseudocyst and the second, between the stomach and exterior, acted as a percutaneous gastrostomy. The initial drain was left in situ for 14 days, at which time it was exchanged percutaneously for the definitive PCG; a double ended Mallecot type catheter that drained between the pseudocyst and the stomach. The latter catheter was left in situ until there was no residual pseudocyst demonstrated on computerized tomography scan and was removed endoscopically. Eleven patients with large (> 6 cm), symptomatic pseudocysts have been treated with PCG. All patients were treated successfully without the need for surgical intervention. The median time to radiological resolution was 24 days. There were four episodes of sepsis, two related to central venous line infections nad two related to catheter blockage. Percutaneous, cystogastrostomy blockage was managed by either replacing the initial drain or inserting a second catheter. The median follow up after successful treatment was 9 months (range 2 17). There were no symptomatic recurrences and one small (2 cm) asymptomatic recurrent pseudocyst. This preliminary experience with PCG demonstrates the efficacy of this procedure for treating symptomatic pancreatic pseudocysts. PMID- 8363479 TI - Computer assisted diagnosis of the acute abdomen. AB - Computer assisted diagnosis (CAD) has been claimed to improve the accuracy of assessment of the acute abdomen. Alternative techniques that may improve decision making are briefly reviewed and CAD is examined critically. The structured collection of complete clinical data with performance feedback, results in improvements comparable to CAD. Computer systems are costly and when installed are used selectively and variably by clinicians. Their place in surgical practice remains to be established. PMID- 8363480 TI - Leiomyosarcoma of the rectum and anal canal. AB - Leiomyosarcoma of the rectum and anal canal is rare and the optimal treatment is not clear. Eight patients with isolated anorectal leiomyosarcoma treated surgically were reviewed. The age ranged from 44 to 76 years (median 63 years) and the follow up ranged from 6 months to 4.5 years (median 2 years). All patients were symptomatic at presentation. All tumours involved the muscularis propria of the low and/or mid-rectum with three tumours also involving the anal sphincters. The tumour size ranged from 1.2 to 10 cm (median 4 cm). Mucosal involvement occurred in only three patients and there was no lymph node involvement. All showed microscopic infiltration at the advancing border, despite macroscopic circumscription. Only one patient was thought to have a tumour sufficiently small (3 cm) and localized on clinical and intrarectal ultrasound examinations (UST2N0) to be suitable for wide local excision. That patient remained tumour-free after 2 years. The remaining patients (88%) were treated by abdomino-perineal resection. The disease free interval in this latter group ranged from 3 months to 4.5 years. All recurrences were detected within 15 months of surgery and the mean interval from detection of recurrence to death was 9 months. Using a histological grading system that included tumour differentiation, mitotic count and amount of necrosis, high grade sarcomas were associated with a worse prognosis. Other factors associated with a poor outcome included large tumour size (> 6-7 cm) and prior incomplete local excision. PMID- 8363481 TI - Common bile duct calculi at laparoscopic cholecystectomy: a technique for management. AB - Laparoscopic cholecystectomy was attempted in 150 unselected patients. The use of routine intraoperative cholangiography prevented serious bile duct injury in one patient. It also showed 75% of patients suspected pre-operatively of having common duct stones, had passed them by the time of cholecystectomy. Eight of 12 diagnosed duct stones (5 suspected, 7 unsuspected) were removed laparoscopically. A technique is described using inexpensive and readily available equipment that allows the transcystic duct treatment of the majority of common duct stones. The development and use of such techniques to laparoscopically treat duct stones will once more allow surgeons to treat all biliary calculi at the one procedure and reduce unnecessary dependence on endoscopic retrograde cholangiopancreatography/sphincterotomy. PMID- 8363482 TI - Left lateral laparoscopic cholecystectomy and its relevance to choledocholithiasis. AB - One of the current challenges to the laparoscopic biliary surgeon is the management of bile duct stones. While laparoscopic bile duct exploration is in its infancy, pre- and postoperative endoscopic retrograde cholangiopancreatography with or without endoscopic papillotomy (ERCP/EP) currently plays a significant role. Intra-operative ERCP/EP has advantages over pre- and postoperative ERCP/EP; however it has not gained popularity due, partly, to the difficulties associated with ERCP/EP being performed with the patient in the supine position. This study prospectively assessed, in 10 consecutive patients, the feasibility of performing laparoscopic cholecystectomies in the left lateral position, a position amenable to intra-operative ERCP/EP if necessary. It is concluded that laparoscopic cholecystectomy in the left lateral position can be performed safely, with similar ease and results as in the supine position, increasing the options available to manage choledocholithiasis. PMID- 8363483 TI - Evaluation of a method to teach cardiothoracic surgery to medical students. AB - This report describes a method to teach undergraduate students the knowledge base and skills needed to maximize the educational value of a subsequent cardiothoracic surgical clerkship. Sixty-three fourth year medical students underwent a structured teaching programme in which groups of five students rotated through a series of six teaching stations. Subject material, presented during 20 min at each station, covered the key issues relating to coronary artery disease, congenital heart disease, chest trauma, lung cancer, prosthetic heart valves, pacemakers, thoracic sepsis and dysphagia. Group knowledge increased significantly (P < 0.001) from a mean mark of 23% (s.d. 12) in a pre-test to a mean mark of 46% (s.d. 12) in a test conducted 1 month after the teaching. The time taken to conduct the structured teaching/assessment was 5 h compared with 32 h to run the same programme by the traditional ward tutorial system. The dollar cost to stage the structured teaching was less than that to run the traditional tutorial programme. It was concluded that the teaching method is effective, economical and practical and that it has a role in an undergraduate curriculum to prepare students for clinical clerkship. PMID- 8363484 TI - The probability of passing at resits in the Part I Fellowship examination. AB - The study aimed to determine the relationship of a candidate's attempt number and proximity of the aggregate score to the pass mark, individually and in combination, to the probability of passing at the next attempt at the Part I FRACS examination. The results of 36 examinations, in which 3513 candidates sat 5891 tests, were analysed. While 40.5% of all candidates who sat these examinations passed, the first attempt pass rate was 44%. Overall about one-third of the candidates who had sat the examination previously passed at the next attempt, the probability of passing remained fairly constant up to the fourth attempt and fell thereafter. As expected, the further the candidate's aggregate score was below the pass mark, the lower the probability of passing at the next attempt. Considering both attempt number and proximity to the pass mark, probability of passing decreased with successive attempts except for very weak candidates. The results indicate that, while the imposition of an upper limit on the number of resits at the examination is not justified, candidates who fall significantly below the pass mark should be advised against resitting for a reasonable period, and those who repeatedly do so should be advised against resitting for a reasonable period, and those who repeatedly do so should another career. It is suggested that feedback to the candidates about the probability of passing at the next attempt be based on the results obtained in this study. PMID- 8363485 TI - Removal of bulky tissue at laparoscopic surgery. PMID- 8363486 TI - Ocular melanoma in childhood. AB - A case of primary ocular melanoma of the iris in a 10 year old girl is reported. Primary melanoma of the eye is exceedingly rare in childhood. The incidence and risk factors for ocular melanoma are discussed and possible reasons why this tumour is so uncommon in younger age groups are considered. PMID- 8363487 TI - Carcinoid syndrome secondary to a primary tumour in a Meckel's diverticulum. PMID- 8363488 TI - Laparoscopic removal of a pelvic endometrioma attached to the ureter. PMID- 8363489 TI - Dentures: difficult oesophageal foreign bodies. AB - Oesophageal foreign bodies occur commonly, but dentures are swallowed infrequently. Two cases are reported that demonstrate the difficulties in the localization and retrieval of ingested dentures, because they are radiolucent and have an awkward shape. Early rigid oesophagoscopy is recommended as the most appropriate investigation and method of removal. PMID- 8363490 TI - Papillary carcinoma arising in a thyroglossal cyst. AB - Carcinoma arising in a congenital thyroglossal cyst is rare, with less than 150 cases reported worldwide. This is a case report of a papillary carcinoma arising within a thyroglossal cyst in a 51 year old woman. Management of this condition remains controversial. Most of these tumours arise from ectopic thyroid tissue within the cyst. Prognosis is good as metastasis is uncommon. Sistrunk procedure is adequate if histology does not reveal extracystic extension. PMID- 8363491 TI - Bifrontal meningeal fibrosarcoma in a patient with metastases to the liver, kidneys and suprarenal glands. AB - Primary meningeal sarcoma is a rare malignant tumour of the central nervous system and metastases to the liver, kidney and the suprarenal gland have not been reported elsewhere. A 47 year old Chinese woman who presented with a short history of headache and vomiting was found to have metastatic meningeal fibrosarcoma in the liver 4 months after resection of primary bifrontal meningeal fibrosarcoma. The computerized tomography findings and relevant histology are presented. PMID- 8363492 TI - Virulence of Salmonella typhimurium mutants for White Leghorn chicks. AB - A strain of Salmonella typhimurium that is highly virulent for 1-day-old white leghorn chicks was genetically modified by deletion (delta) of the adenylate cyclase (cya) and cyclic AMP receptor protein (crp) genes or by removal (curing) of the 91-kilobase virulence plasmid. These mutants were then compared with the wild-type S. typhimurium strain for virulence in 1-day-old chicks and for their ability to colonize chicks of various ages. The plasmid-cured mutant showed a slight reduction in virulence, whereas the delta cya delta crp mutant was completely avirulent. The wild-type strain and both mutant strains were capable of colonizing various organs within the chicks. At all time points, the delta cya delta crp strain colonized chicks at lower levels than the wild-type strain. Titers of the plasmid-cured strain increased more slowly in visceral organs than did those of the wild type. PMID- 8363493 TI - Effects of vitamin A deficiency on the reproductive system of mature White Leghorn hens. AB - Two groups of 100 white leghorn hens were fed rations either supplemented or deficient in vitamin A for 32 weeks. At the conclusion of the study, vitamin A supplemented hens laying normally were also compared with a group of vitamin A supplemented hens in a state of low egg production. Mean egg retinol equivalents (microgram retinol/g egg yolk), egg production, and hatchability in the vitamin A deficient group were decreased significantly by 4, 20, and 28 weeks, respectively, after beginning treatment. The ovaries of vitamin A-deficient chickens had increased numbers of atretic follicles compared with the ovaries of vitamin A-supplemented hens (20, 24, 28, and 32 weeks), and these atretic follicles contained moderate to severe hemorrhage. Hemorrhage was located either uniformly throughout the follicle or more commonly between the detached granulosa cell layer and the theca interna. Hemorrhagic follicles were uncommon in both vitamin A-supplemented hens and low-production vitamin A-supplemented hens. PMID- 8363494 TI - Heterophil chemotaxis in chickens with natural Staphylococcal infections. AB - Heterophil chemotaxis using heterophils isolated from the peripheral blood of five commercial broiler chickens naturally infected with staphylococcal bacteria was compared by the modified Boyden-chamber technique with chemotaxis of heterophils from two chickens from the same flock not infected with Staphylococcus (field controls) and from four healthy laboratory control broiler chickens. The infected chickens had gross and histologic lesions of staphylococcal tenosynovitis and osteomyelitis. Staphylococci were isolated from the lesions. Hematologic parameters and histologic lesions of infected chickens also were examined. Compared with field and laboratory controls, Staphylococcus infected chickens had heterophilic leukocytosis. The heterophils of Staphylococcus-infected chickens had significantly lower chemotactic activity than both control groups in terms of random movement and directed chemotactic movement in response to stimulus. Toxic changes were observed in heterophils of some of the Staphylococcus-infected broilers. PMID- 8363495 TI - Development of immunity in broilers continuously exposed to Eimeria sp. AB - A series of experiments was conducted to determine the time required to induce absolute immunity to three species of Eimeria in young broiler chickens continuously exposed to the parasite. Acquisition of immunity was measured by cessation of oocyst production in each bird. Initial experiments were performed in broilers beginning at age 7 days with continuous oocyst administration for 28 days with E. tenella, E. maxima, or E. acervulina. Evaluation of oocyst production demonstrated a major decline in oocyst output of E. maxima and E. tenella by 2 weeks, with cessation by 25 days. Exposure to E. acervulina caused cessation of oocyst production by day 16. To study whether chickens of different ages varied in their capacity to immunize within this time frame, 1-day-old birds also were studied. For E. tenella, exposures also were initiated in 14- and 21 day-old birds. This study demonstrated that regardless of the age of the broiler, all were capable of establishing complete protective immunity to E. tenella, E. maxima, and E. acervulina under continuous exposure within 25, 24, and 16 days, respectively. PMID- 8363496 TI - Tibial dyschondroplasia of chickens induced by Fusarochromanone, a mycotoxin. AB - Chicks were fed for 3 weeks a practical broiler starter diet amended with fusarochromanone (FC), a mycotoxin. In Hubbard broiler chicks, the highest test dose of FC (75 ppm) suppressed body weight by 33% and humoral response to sheep erythrocytes by 34% to 50%, and increased the incidence of tibial dyschondroplasia (TD) to 100%. The intermediate dose (35 ppm) significantly increased the incidence of TD in both types of broiler chicks (Hubbard and Indian River), but its effect on humoral response to sheep erythrocytes was not consistent across several experiments. A minimum dietary concentration greater than 20 ppm was required to significantly increase the incidence of TD. Excessive dietary copper or zinc (200 ppm) alleviated the effect of FC on TD. However, activities of copper-dependent ceruloplasmin and superoxide dismutase was not affected by FC. Cartilage mineral profiles in FC- or Thiram-induced TD differed from that of 1-day-old hypertrophic embryonic cartilage core (less K and Mn). FC did not induce TD in leghorn chicks. PMID- 8363497 TI - Characterization of isolates of Haemophilus paragallinarum from Argentina. AB - The biochemical and serological properties of Haemophilus paragallinarum isolates recovered from 11 recent outbreaks of infectious coryza in layer hens and one case of swollen-head syndrome in broilers in Argentina are described. Twenty-four isolates had the typical biochemical properties of H. paragallinarum. All isolates were serotyped according to the Page scheme. Ten of the isolates were serovar A, 11 were serovar B, one was serovar C, and two isolates could not be serotyped. The isolates were also examined using a panel of monoclonal antibodies (MAbs) for Page serovars A (one MAb available) and C (three MAbs available). The serovar B isolates all failed to react with any MAb. The serovar C isolate reacted with all three serovar C MAbs but not with the serovar A MAb. Only six of the 10 serovar A isolates reacted with the serovar A MAb. These results indicate that H. paragallinarum isolates from Argentina are antigenically distinct from those examined in other countries, and it is suggested that coryza vaccines intended for use in Argentina may be more effective if based on local strains. PMID- 8363498 TI - A sequential histopathologic and immunocytochemical study of chicken anemia virus infection at one day of age. AB - Detection systems for chicken anemia virus (CAV) antigen in paraffin sections were evaluated. Mouse monoclonal antibodies to CAV used in conjunction with an avidin-biotin-peroxidase-complex detection system gave best results. Immunoreactivity of CAV was markedly affected by fixation. Fixation in neutral buffered formalin for 6 hours gave best results. Use of decalcifying fluid containing formic acid eliminated immunoreactivity of CAV, whereas use of an EDTA solution did not. In a sequential study, CAV antigen and lesions were first detected in bone marrow, thymus, and spleen at days 3-4 postinoculation (PI). Subsequently, antigen and/or cells containing nuclear inclusions were found in many tissues, but usually within lymphoid tissue therein. Thymus, spleen, bone marrow, proventriculus, and ascending duodenum contained most antigen. No antigen was detected after 26 days PI. The results indicated that CAV replicates in thymic lymphoblasts, intra- and extra-sinusoidal hemocytoblasts, and reticular cells, with consequent lymphocytic depletion of the thymic cortex and hypoplasia of the bone marrow, and that CAV antigen is widely distributed in the body. PMID- 8363499 TI - Characterization of Salmonella california and S. typhimurium strains with reduced ability to colonize the intestinal tract of broiler chicks. AB - This study determined the ability of eight strains of Salmonella and their agarsubcultured variants to colonize the intestinal tract of broiler chicks. Nalidixic-acid (NAL)-resistant and streptomycin-resistant subcultured strains (S. california 1989/A and S. typhimurium 3366/A) that persisted in the ceca of chicks in lower numbers than their NAL-resistant parent strains (1989/O and 3366/O) were selected for additional study S. typhimurium strain 3366/A was present in the ceca of chicks in lower numbers than the parent strain 3366/O when given concomitantly with the parent strain or when the two strains were given separately to different chicks. S. california 1989/A strain was present in the ceca in lower numbers than the parent strain after concomitant oral or intracloacal inoculation. Strains 3366/O and 3366/A of S. typhimurium differed in growth rates in BHI broth and cecal mucus. The lipopolysaccharide (LPS) profile indicated that LPS components present in S. california 1989/O were missing from strain 1989/A. A mutant of 1989/O--2095/R--was also LPS- and colonization deficient. PMID- 8363500 TI - Avian Eimeria: effects of gamma irradiation on development of cross-species immunity in foreign and natural host birds. AB - Repeated inoculation (immunization) of white leghorn chickens with oocysts of the turkey coccidium, Eimeria adenoeides, resulted in significantly improved weight gain and feed-conversion ratios (feed efficiency) after E. tenella challenge. However, the development E. tenella in the immunized chickens did not differ markedly from that in unimmunized chickens, and intestinal lesions remained severe (greater than 3.0). Apparently improved weight gain and feed efficiency can be maintained in the presence of extensive parasite development. The ability to elicit cross-protective immunity was abrogated when the E. adenoeides oocysts were exposed to 15 kRad of gamma irradiation before inoculation into the chickens. Sporozoites existing from irradiated oocysts of E. acervulina also failed to immunize the chickens against challenge with E. tenella but protected chickens almost completely against homologous challenge with E. acervulina. The results indicate that cross-species immunity is not elicited by all developmentally arrested sporozoites and that the ability to produce cross species immunity can be destroyed by gamma irradiation of the immunizing species. PMID- 8363501 TI - Effects of chicken anemia virus on macrophage function in chickens. AB - One-day-old chicks were inoculated intramuscularly with chicken anemia virus (CAV). Four birds were killed at 7, 14, 21, 28, and 42 days postinoculation (PI), and macrophages were recovered from spleen and bone-marrow suspensions. These were tested for interleukin-1 (IL-1) production, Fc receptor expression, phagocytosis, and bactericidal activity. Macrophages recovered from uninoculated chickens at the same sample times, and exposed to CAV in vitro, were also tested. IL-1 production, Fc receptor expression, phagocytosis, and bactericidal activity were significantly lower in all macrophage cultures from CAV-inoculated chickens, and in cultures exposed to the virus in vitro, than in uninfected controls. PMID- 8363502 TI - Effects of chicken anemia virus on cell-mediated immune function in chickens exposed to the virus by a natural route. AB - Three-week-old chicks were inoculated orally with CAV and killed at various times postinoculation (PI). The spleens were removed, the cells were stimulated with concanavalin A, and lymphocyte transformation responses were determined. Supernatants from these cultures were also assayed for T-cell growth factor (TCGF) and interferon. Adherent macrophages from spleen or bone marrow were assayed for interleukin-1 production, Fc receptor expression, phagocytosis, and bactericidal activity. All CAV-inoculated chickens developed CAV antibodies, but no anemia was seen. Controls remained CAV-antibody-negative throughout the experiment. CAV-inoculated chickens showed significant differences from controls in their lymphocyte transformation responses and in production of TCGF and interferon. Differences were greatest at 14, 21, and 28 days PI. Significant differences were also observed in interleukin-1 production by spleen macrophages, as well as in Fc receptor expression, phagocytosis, and bactericidal activity of bone-marrow macrophages. PMID- 8363503 TI - Identification of the putative cytadhesin gene of Mycoplasma gallisepticum and its use as a DNA probe. AB - A portion of the putative Mycoplasma gallisepticum (MG) cytadhesin gene was identified and used as a diagnostic DNA probe. Degenerate oligonucleotide primers corresponding to conserved regions of the cytadhesin proteins from two human mycoplasmas, M. pneumoniae and M. genitalium, were synthesized for use in the polymerase chain reaction (PCR) on genomic MG DNA. A 583-base-pair MG DNA fragment was amplified and subsequently cloned and sequenced. The MG DNA fragment is predicted to encode a 193-amino-acid peptide. This peptide demonstrates significant homology to the expected portions of the two human mycoplasmal cytadhesin proteins. Used as a probe to study the distribution of this fragment in pathogenic and nonpathogenic avian mycoplasmas, the PCR product hybridized to genomic DNA from all seven MG strains tested. However, it failed to hybridize to M. synoviae, M. meleagridis, M. iowae, or M. gallinarum DNA. PMID- 8363504 TI - Effect of short-chain fatty acids on the growth of Salmonella typhimurium in an in vitro system. AB - Previous studies have revealed a reduction of cecal Salmonella carriage from feeding either carbohydrate or short-chain fatty acids (SCFAs). This in vitro study presents a profile of the relative SCFA content of the ceca when chicks are fed an unmedicated diet with 2.5% carbohydrate. Subsequent incorporation of these acids into culture medium was used to demonstrate their antagonistic activity toward in vitro growth of Salmonella typhimurium. Commonly found concentrations of SCFAs based upon the above findings reduced in vitro Salmonella growth by at least 50%, and 10 x concentrations inhibited growth more than 80%. An explanation of the mechanism(s) involved in growth reduction is offered. PMID- 8363505 TI - Efficacy of experimental animal and vegetable oil-emulsion vaccines for Newcastle disease and avian influenza. AB - Acceptable oil-emulsion vaccines were sought to replace mineral oil-emulsion vaccines that, by regulations, require a 42-day minimum holding period for poultry between injection and slaughter for consumption. Water-in-oil emulsions were prepared using animal or vegetable oils in a ratio of 4 parts oil to 1 part Newcastle disease or avian influenza aqueous antigen. Beeswax particles suspended in the oil at the 5% or 10% level (wt:vol) served as the oil-phase surfactant. Hemagglutination-inhibition titers induced by mineral-oil vaccines were not significantly different from those induced by the most efficacious formulations prepared from animal and vegetable oils. Tissue reaction from injection of animal and vegetable-oil vaccines was less than that induced by mineral-oil vaccines. An inactivated avian influenza vaccine formulated from peanut oil induced protection against morbidity and death when vaccinated chickens were challenged with a virulent isolate of avian influenza virus. PMID- 8363506 TI - Effect of induced molting on the susceptibility of White Leghorn hens to a Salmonella enteritidis infection. AB - Older white leghorn hens (more than 52 weeks old) were induced to molt using a 14 day feed-removal protocol. On day 4 of feed removal, groups of hens were infected with varying 10-fold dilutions of Salmonella enteritidis, and these hens were examined for S. enteritidis intestinal shedding 7 days later. Molting hens infected with a 10(-2) dilution of S. enteritidis shed 3-4 logs more of the organism at 7 days postinfection than the unmolted group receiving a similar dose. The mean infectious dose (ID50) for S. enteritidis in unmolted hens ranged from 0.65 x 10(4) to 5.6 x 10(4), whereas in molting hens the ID50 was found to be less than 10(1), a 2-3 log increase in the susceptibility of the hens to the organism. PMID- 8363507 TI - Effect of Vibrio cholerae toxin on oral immunization of chickens. AB - Cholera toxin from Vibrio cholerae has been shown to increase the secretory immune response when given orally with some antigens in mice and rabbits. The present study was designed to determine if cholera toxin was also an effective mucosal adjuvant in chickens. Tetanus toxoid was chosen as a model antigen, and response was measured by enzyme-linked immunosorbent assays of intestinal excreta, bile samples, and serum samples. Chickens given 20 micrograms of tetanus toxoid had a significant suppression of response when 20 or 50 micrograms of cholera toxin was given. Chickens given 100 micrograms of tetanus toxoid appeared to be mucosally tolerant, but there was apparent abrogation of the mucosal tolerance when 20 or 50 micrograms of cholera toxin was given. Cholera toxin apparently failed as a mucosal adjuvant in chickens but may have some anti mucosal tolerogenic effect. PMID- 8363509 TI - Enteritis (so-called runting stunting syndrome) in Georgia broiler chicks. AB - So-called runting stunting syndrome (RSS) afflicts chicks worldwide. The present study in Georgia chicks is the first report of unique histologic features of RSS pathology in chicks in the United States. Various combinations of avian nephritis virus, enterovirus-612, and reovirus were always isolated from chick small intestines. Ultrastructurally, only small round viruses were seen in small intestinal lesions. Although finding intralesional virus in small intestinal segments from chicks with signs and gross lesions consistent with RSS constitutes a reasonable criterion for making a diagnosis of this disease, chicks without intralesional viruses and with bacterial or protozoal enteritis may also be small and abnormally feathered. Because just what constitutes RSS remains a diagnostic dilemma, we recommend that the use of the imprecise acronym "RSS" be discontinued. PMID- 8363508 TI - Immunohistochemical detection of Newcastle disease virus in chickens. AB - An immunoperoxidase histochemical technique utilizing a monoclonal primary antibody was developed for detection of Newcastle disease virus (NDV) antigen in tissues from chickens. The technique was applied to trachea, lung, spleen, Harderian gland, and cecal tonsil harvested from specific-pathogen-free (SPF) chickens at 2, 5, 7, 10, and 14 days postinoculation (PI) with NDV, and to corresponding tissues from commercial broiler chickens representing 30 cases of spontaneous respiratory disease. Positive staining occurred in the cytoplasm of respiratory epithelial cells in the trachea or bronchi of NDV-inoculated SPF chickens at 5 and 7 days PI. Staining also occurred in the respiratory epithelium of the trachea and bronchi of commercial broilers from seven of 30 cases of spontaneous respiratory disease. These results indicate that the immunoperoxidase technique has value as a rapid diagnostic test for Newcastle disease. PMID- 8363510 TI - Local pathological reactions and immune response of chickens to ISA-70 and other adjuvants containing Newcastle disease virus antigen. AB - Chickens were examined for gross and microscopic changes at the injection site for 16 weeks after an intramuscular injection of the following oil adjuvant emulsions containing inactivated Newcastle disease virus (NDV) antigen: ISA-70, Freund's incomplete adjuvant (FIA), Freund's complete adjuvant (FCA), and aluminum phosphate gel (APG). The reactions induced by ISA-70 emulsion were characterized by proliferation of macrophages, epithelioid cells, and fibroblasts around the small cysts in the muscle. Infiltration of lymphocytes and plasma cells also was present. These changes peaked 2 weeks postinjection and were milder than lesions due to the Freund's adjuvants. FCA induced the most severe granulomatous lesions with abscess formation. The reactions to APG were characterized by proliferation and accumulation of macrophages. The serological results revealed that the enhancing effect of ISA-70 on NDV antigen was the same as that of FIA. PMID- 8363511 TI - Determination of the detection limit of the polymerase chain reaction for chicken infectious anemia virus. AB - Chicken infectious anemia virus (CIAV) DNA in infected cell cultures and chicken tissues was detected using a polymerase chain reaction (PCR) assay. The complete CIAV genome of several strains was amplified in two segments with two sets of primer pairs. The DNA segments of four CIAV strains and full-length Cux-1 strain DNA were cloned. After amplification, 100 original genome equivalents were detected by Southern hybridization. The sensitivity of the assay was enhanced considerably by performing a reamplification with nested primers. This modification permitted the detection of one molecule of CIAV DNA. Some problems of the assay and its possible application are discussed. PMID- 8363512 TI - A lipid-conjugated immunostimulating complex subunit vaccine against Salmonella infection in turkeys. AB - Immunostaining complexes (ISCOMs) are multimeric particles and have been used successfully for presentation of membrane proteins. In this study, outer-membrane proteins (OMPs) from Salmonella heidelberg were incorporated into lipid conjugated ISCOM particles and evaluated for their use in a vaccine for turkeys against homologous and heterologous Salmonella challenge. Two types of lipid conjugated ISCOMs were examined: ISCOM-phospholipid and ISCOM-sphingolipid preparations. The turkeys were challenged with one of the three Salmonella serotypes: S. heidelberg, S. reading, or S. enteritidis. The turkeys were monitored for clinical signs, shedding pattern post-challenge, and clearance of the challenge Salmonella from selected internal organs. Vaccines containing OMP with either lipid-conjugated ISCOM preparation produced significantly greater (P < 0.01) immune response than OMP alone. Cloacal swabs from turkeys given OMP along with ISCOM-phospholipid and challenged with a homologous serotype were completely negative for Salmonella. A certain degree of cross-protection against heterologous Salmonella was afforded by both OMP-ISCOM vaccines. The isolation rate of Salmonella from internal organs was significantly lower (P < 0.0001) in vaccinated turkeys than in unvaccinated controls. PMID- 8363513 TI - Depletion of CD4+ and CD8+ T lymphocyte subpopulations by CIA-1, a chicken infectious anemia virus. AB - The suppressive effect of chicken infectious anemia virus (CIAV) on T-lymphocyte subpopulation was evaluated in vivo by flow cytometry and dual immunostaining on frozen sections. Between 14 and 21 days postinoculation (PI), the percentage of CD4-, CD8-, and CT1-positive (CD4+, CD8+, and CT1+) cells was significantly lower in chickens infected at 1 day of age with CIA-1 strain of CIAV than in controls. The mean percentage of CD4+ cells in the thymus was only 43%, whereas in the controls it was 77%. The mean percentages of CD8+ cells in the thymus in infected and control chickens was 54% and 90%, respectively, and of CT1+ cells, 44% and 92%, respectively. At 28 days PI, the percentage of CD4+, CD8+, and CT1+ cells was similar in infected and control chickens. Also at 14 and 21 days PI, immunoperoxidase staining demonstrated fewer CD4+, CD8+, and CT1+ cells in the thymus of infected chickens than in controls. In frozen sections of thymus stained with CIA-1 antibodies and CD4, CD8, or CT1, few of the cells positive for CIAV antigen seen in the outer zone of the cortex carried CD4, CD8, or CT1 molecules. These results suggest that CIA-1 infection either destroys cells expressing CD4, CD8, or CT1 molecules on their surface or interferes with the expression of these molecules. PMID- 8363514 TI - Monoclonal antibody-based detection system for Salmonella enteritidis. AB - Two monoclonal antibodies that react with Salmonella enteritidis in chicken tissue, eggs, and environmental samples were used to develop a rapid enzyme linked immunosorbent assay (ELISA) screen and agglutination assay for the specific detection of S. enteritidis. S. enteritidis was detected in 100% of egg samples and 99.8% of various field and research samples by both ELISA and traditional microbiological isolation and identification techniques. Results of titer experiments indicate that as few as 10(4) organisms can be detected by ELISA. PMID- 8363515 TI - Antibody prevalence and isolation of Chlamydia psittaci from pigeons (Columba livia). AB - The isolation of Chlamydia psittaci and serological detection of Chlamydia specific antibodies in racing pigeons and pigeons from public parks is described. Several serological methods (complement fixation test, indirect microimmunofluorescence test, and enzyme-linked immunosorbent assay) were compared with bacteriological techniques (isolation both in embryonated eggs and McCoy cell monolayers). Tests confirmed that 28.6%, 33.5%, and 35.9% of the pigeons, respectively, were seropositive by the tests mentioned above. Chlamydiae were isolated from 13% of the fecal specimens in ovocultures and from 18% of the fecal specimens in cell cultures. No significant differences between the two groups of pigeons were found (at a 95% confidence level, alpha = 0.05) using the hypothesis test of the difference between proportions of two populations. The serological and bacteriological techniques used are compared and discussed. PMID- 8363516 TI - Effect of mixed cecal microflora maintained in continuous culture and of dietary lactose on Salmonella typhimurium colonization in broiler chicks. AB - Mixed cecal microflora obtained from a mature chicken were maintained in vitro in continuous-flow (CF) culture. The effect of the CF culture and dietary lactose on Salmonella typhimurium cecal colonization in broiler chicks was evaluated. When averaged across four replicates, chicks treated with the culture alone (1.75 log10 decrease) or with 5% dietary lactose alone (2.98 log10 decrease) were protected against S. typhimurium. Optimum protection against S. typhimurium was observed when birds were treated with the culture in combination with dietary lactose (4.27 log10 decrease). Dietary lactose resulted in reduced cecal pH. A large increase in cecal propionic acid was observed in the birds given the CF culture. A significant correlation (P < 0.001) was observed between the cecal concentration of undissociated propionic acid and protection against S. typhimurium colonization (r = -0.78). The results indicated that indigenous cecal flora that protect against Salmonella colonization can be maintained without loss of efficacy in CF culture. PMID- 8363517 TI - Staphylococcosis of turkeys. 6. Development of penicillin resistance in an interfering strain of Staphylococcus epidermidis. AB - Staphylococcus epidermidis strain 115, used as an interfering agent to help reduce the incidence of staphylococcosis in turkeys, was converted into a penicillin- and chloramphenicol-resistant strain designated 115R. This was accomplished by introducing a plasmid carrying the beta-lactamase (penicillinase) and chloramphenicol-resistance genes into S. epidermidis 115 by electroporation. The resultant strain, 115R, was an efficient producer of beta-lactamase and had marked increased resistance to penicillin and chloramphenicol. A beta-lactamase DNA probe was used to confirm the presence of the beta-lactamase gene in strain 115R. S. epidermidis strain 115R retained the characteristics of tissue adherence, bacteriocin production, and non-virulence that were present in the original non-transformed strain 115, and in addition should theoretically remain colonized in poults following treatment with penicillin. PMID- 8363518 TI - Effect of so-called chicken anemia agent maternal antibody on chick serologic conversion to viruses in the field. AB - Chicken anemia agent (CAA)-antibody-positive and -negative broiler chicks and specific-pathogen-free chicks were confined in six broiler houses. Data on seroconversion to common avian pathogens and production performance were collected. No significant differences were seen between CAA-antibody-positive and -negative chickens in geometric mean antibody titers against common avian pathogens or in production performance. PMID- 8363519 TI - Virus isolation accuracy: an evaluation of eight laboratories involved in poultry diagnostics. AB - A study was undertaken to evaluate the accuracy of diagnostic laboratories at isolation of common avian viral pathogens. Fourteen "unknown" samples were submitted to eight laboratories in seven states. All positive and negative samples were guaranteed pure by SPAFAS. Virus-isolation results were erroneous in many cases. Based on this study, it appears that protocol for virus isolation of avian pathogens should be standardized throughout the United States. PMID- 8363520 TI - Characterization of Haemophilus paragallinarum isolates from China. AB - The biochemical and serological properties of 11 isolates of Haemophilus paragallinarum from outbreaks of infectious coryza in the People's Republic of China are described. All 11 isolates had the typical biochemical properties of H. paragallinarum, and all belonged to Page serovar A. PMID- 8363522 TI - Verminous encephalitis apparently caused by the filarioid nematode Chandlerella quiscali in emus (Dromaius novaehollandiae). AB - Verminous encephalitis attributed to Chandlerella quiscali was diagnosed in a flock of emus (Dromaius novaehollandiae). Clinically affected birds showed torticollis and progressive ataxia. Filarioid parasites with morphological characteristics resembling C. quiscali were identified in one case. Histologic lesions in the brain and spinal cord consisted of mild to moderate perivascular cuffing and scattered areas of variable mild necrosis. Parasites observed within the parenchyma of the brain and spinal cord often were not associated with either necrosis or an inflammatory reaction. Ivermectin administered subcutaneously at 4 week intervals at a dose rate of 200 micrograms/kg body weight appeared to prevent clinical signs in flocks in the presumed endemic area. PMID- 8363523 TI - Acute hemorrhagic enterocolitis in ratites: isolation of eastern equine encephalomyelitis virus and reproduction of the disease in ostriches and turkey poults. AB - Two emus died with acute hemorrhagic enterocolitis. Eastern equine encephalomyelitis (EEE) virus was isolated in Vero cells from non-pooled samples of brain and intestine. Enterocolitis with splenic and hepatic necrosis was reproduced by intramuscular or oral inoculation of this isolate in two ostriches and three turkey poults. PMID- 8363521 TI - Paralysis of undetermined origin in bobwhite quail. AB - Paralysis of undetermined etiology occurred in a group of pen-reared bobwhite quail. Other than severe dehydration, no gross or microscopic lesions were observed, and the cause was not identified. Fumonisin B1 was detected in the feed at 17.7 ppm. In an attempt to reproduce the condition, a feeding trial was conducted utilizing the suspect feed. The feeding trial was not successful in reproducing the symptoms observed in the field case. PMID- 8363524 TI - Isolation of Mycobacterium avium from ringneck pheasants (Phasianus colchicus). AB - Tuberculous lesions were observed at necropsy in the liver, spleen, and intestine of five 10-month-old ringneck pheasants (Phasianus colchicus) from a flock of birds raised in captivity for breeding. Histological examination of the tissues revealed granulomas with associated acid-fast bacilli. The history and lesions are unusual in that very few bacteria were found in any given lesion, the birds were all in good flesh when necropsied, and five birds from this same group at 6 months of age were observed to have acid-fast bacteria in the small intestine. Mycobacterium avium was isolated and serotyping was attempted, but the colonies were too dry to serotype. PMID- 8363525 TI - Characteristics of fowl cholera diagnosed in Georgia, 1989-91. AB - One hundred seventy-six cases of fowl cholera were diagnosed at the Georgia Poultry Laboratory over a 3-year period. The disease occurred throughout the year, with peak incidence during March and April. Fowl cholera was diagnosed in flocks from 4 to 83 weeks of age, with a mean of 33 weeks of age. The Pasteurella multocida isolates were highly susceptible to all antimicrobial agents tested, except sulfonamides. The serotypic distribution of isolates showed that serotype 3,4 predominated (40%), followed by serotype 3 (22%), serotype 1 (18%), untypable (15%), serotype 5 (3%), and serotype 4 (2%). Associations were found between the P. multocida serotypes isolated from birds of different ages and between the age of the bird and the sites of choice for isolating the organism. PMID- 8363526 TI - Coumafuryl (Fumarin) toxicity in chicks. AB - Coumafuryl (Fumarin) toxicity was diagnosed in chickens less than 1 week of age. Mortality rate was 100%. Necropsy showed crops and gizzards to be full of feed. There was diffuse hemorrhage and unclotted blood in the abdomen and thorax. Histological examination showed congestion and hemorrhage. Chemical analysis of crop and gizzard contents contained approximately 340 ppm coumafuryl. The source of the coumafuryl was found to be the wood-straw mats in the chick boxes. PMID- 8363527 TI - Pharmacokinetic properties of gentamicin and amikacin in the cockatiel. AB - Gentamicin and amikacin are commonly used in veterinary medicine to treat a variety of gram-negative bacterial infections. The present study evaluates the pharmacokinetics of gentamicin sulfate and amikacin sulfate in the cockatiel (Nymphicus hollandicus), a small (approximate body weight = 100 g) psittacine bird, utilizing treatment regimens developed in larger parrot species. Serum antibiotic concentrations were determined in cockatiels following twice-daily intramuscular treatment with 5 mg gentamicin/kg body weight and 15 mg amikacin/kg body weight. In the present study, peak values of gentamicin were 4.6 +/- 1.45 micrograms/ml, and trough values were 0.17 +/- 0.04 micrograms/ml. Amikacin administration resulted in peak values of 27.3 +/- 6.9 micrograms/ml and trough concentrations of 0.9 +/- 0.3 micrograms/ml. Based on the present study, an appropriate intramuscular dose regimen for gentamicin in cockatiels is 5 to 10 mg/kg body weight either two or three times per day. An intramuscular amikacin dosage of 15 to 20 mg/kg body weight either two or three times per day is recommended for treatment of infections caused by susceptible bacteria. PMID- 8363528 TI - The National Mental Health Policy: implications for public psychiatric services in Australia. AB - The Health Ministers of all Australian States, Territories and the Commonwealth endorsed a National Mental Health Policy in April 1992. This Policy is intended to set a clear direction for the future development of mental health services within Australia. The Policy recognises the high prevalence of mental health problems and mental disorders in the Australian community and the impact of these on consumers, carers, families and society as a whole. It also clearly accepts the need to address the problems confronting the promotion of mental health and the provision of mental health services. PMID- 8363529 TI - On the perception of madness. AB - Since the beginning of recorded history, mental illness has been recognised as being primarily in the province of the healing profession. This view has continued, despite the fact that psychiatry left the mainstream of medicine with the development of asylums during the 19th century. With the advent of deinstitutionalization however, psychiatrists, particularly in Australia, have increasingly left public practice. As a result, the treatment of the severely and chronically mentally ill, especially those with behavioural disorder, has become neglected. It is argued that moves toward the mainstreaming of acute psychiatry to general hospitals offer a new opportunity for the profession to reassert itself in this essential but difficult area of psychiatric practice. PMID- 8363530 TI - Genetic linkage and schizophrenia: methods, recent findings and future directions. AB - Family, twin and adoption studies have shown that familial clustering in schizophrenia is predominantly due to genetic factors. On the basis of segregation analyses of the illness distribution in relatives of patients, various models of the mode of transmission have been put forward but as yet there is no consensus. Linkage analysis based on molecular genetic techniques provides a more direct approach to discovering precisely what is inherited (one gene, a small number of genes or many genes?) that generates vulnerability to schizophrenia. To date there has been no sufficiently replicated finding of one or more linked genes and many methodological complexities remain. However, the rate of progress in addressing these issues gives hope that genetic linkage analysis of schizophrenia will provide some answers. PMID- 8363531 TI - Interethnic variations in the presence of Schneiderian first rank symptoms. AB - Differences in the presence of Schneiderian First Rank Symptoms in first admission schizophrenic patients were examined in five subcultural groupings treated in the same facilities. Examination of the case notes of 212 patients revealed that first rank symptoms were most prevalent in the UK immigrant group and least frequently present in the Greek immigrant group. First rank symptoms were more prevalent in patients admitted recently, admitted voluntarily, and amongst those who had at least some command of English. PMID- 8363532 TI - Borderline disorder and post-traumatic stress disorder: an equivalence? AB - This paper draws attention to various similarities between Borderline Personality Disorder and Post-traumatic Stress Disorder. It is argued that the former may be considered to be an equivalent of the latter, with the difference that the trauma has either undergone repression or, having been suffered before the establishment of speech, has not been registered in verbal form. The criteria for Borderline Personality Disorder are presented in terms of symptoms of failed attachment consistent with early trauma, and various research papers linking these concepts are considered. Other research in infant attachment suggests intergenerational links between disorganised attachment patterns in infancy and parents with unresolved problems with their own parents. Research concerning the biochemical underpinning of emotional responses is quoted to link these conditions more securely, and may offer a conceptual framework in which to understand the need of these patients for a therapeutic milieu in which early developmental needs may be understood. PMID- 8363533 TI - Lithium-associated transient thyrotoxicosis in 4 Chinese women with autoimmune thyroiditis. AB - Four Chinese female patients who suffered from manic-depressive disorder and underlying autoimmune thyroiditis developed transient episodes of thyrotoxicosis during maintenance lithium therapy. Endocrinologically speaking, three of them had "Hashitoxicosis", while the other had silent lymphocytic thyroiditis. Albeit rare among Western patients, such lithium-associated thyroid dysfunctions appeared to be more likely to occur in Hong Kong Chinese. They seemed to involve multiple aetiological factors, such as autoimmune thyroid disease, the toxic and immunomodulatory roles of lithium and perhaps genetic and dietary factors. Because of their self-limiting nature, the importance of avoiding unnecessary and potentially deleterious antithyroid treatment is emphasised. PMID- 8363534 TI - Lessons from a mood disorders unit. AB - Specialist treatment centres, such as the Mood Disorders Unit (MDU) at Prince Henry Hospital, Sydney, have developed in response to the high prevalence of mood disorders and their frequent persistence and treatment resistance. The MDU's assessment and treatment of patients from a state-wide catchment area and its teaching and research effectiveness are reviewed. Of 479 patients assessed between 1985 and 1989, there were 304 with primary depressive disorders, of whom 154 were followed up by clinical assessment at 52 weeks and 231 by telephone interview at 3 1/2 years. At intake, 59% were tertiary referral patients and 88% were from outside the local area. Two-thirds were recovered 3 1/2 years later, despite the disorders having been generally severe and protracted. Treatment modality was associated primarily with diagnosis, but also with age and somewhat with the patient's personality and consultant psychiatrists' preferences. No consistent predictors of outcome were discerned. Specialist tertiary referral centres, such as the MDU, contribute significantly to treatment success, especially of difficult cases, and enrich teaching and research. PMID- 8363535 TI - Parental evaluation of treatment outcome and satisfaction with an inpatient program for eating disorders. AB - This study is concerned with the service provided to adolescent patients with eating disorders admitted to a private hospital. The patients' parents were asked to evaluate the service. Parental satisfaction was assessed by means of a questionnaire devised for this purpose and comments were elicited as to how the service could be improved. Parents of a consecutive series of 56 patients were asked to complete the questionnaire 6 months after admission; 82% (N = 46) responded. Most parents were pleased with the service provided but nevertheless many made some criticisms (35%) or suggestions for improvement (37%). The parental responses were discussed with the staff involved in treatment, resulting in changes to the service. PMID- 8363536 TI - Helping agency contact for emotional problems in childhood and early adolescence and the risk of later disorder. AB - Despite waning enthusiasm for labelling theories in the development of psychopathology, it has been claimed that contact with professional agencies in childhood can be associated with increased levels of later problem behaviour. In this study, help-seeking by parents for children with behaviour problems was examined using a birth cohort followed longitudinally to age 15 years. No evidence was found to support the hypothesis that agency contact increased the risk of later mental health disorder, either in childhood or adolescence. Rather, the results suggested that help-seeking was associated with a reduction in both the risk of DSM-III disorder and problem behaviour scores, up to five years after agency contact. PMID- 8363537 TI - Psychological maladjustment among homeless adolescents. AB - The prevalence of psychological maladjustment in homeless adolescents (n = 54) was compared to a control group (n = 58) in Brisbane, Australia using the Youth Self-Report Scale. Overall, 74% of the homeless group and 22.4% of the control group scored within the clinical range on one or more of the clinical subscales. There was considerable diversity of symptomatology in the homeless group. Less than half of the homeless group were within the clinical range on both the delinquent subscale and the thought disorder subscale. Depressive, Aggressive and Somatic Complaints were also prevalent. The study challenges preconceived notions of a simple relationship between adolescent homelessness and delinquency, and draws attention to the psychological needs of this group of adolescents. PMID- 8363538 TI - Are oppositional and conduct disorders of adolescents separate conditions? AB - This study explores the factor structure of behaviours that correspond to symptoms of DSM-III-R oppositional defiant (OD) and conduct disorder (CD). It also seeks to clarify how those hypothetical factors may relate to diagnoses of OD and CD. Using exploratory factor analysis and cluster analysis of parent questionnaire data from a group of referred adolescents (N = 528) diagnosed according to DSM-III criteria the authors extracted four factors. One of them corresponded closely to DSM-III-R OD, while the others comprised different aspects of the CD construct. The findings suggest there are subtypes of conduct problems in adolescents, and give some support to the distinction between conduct and oppositional disorders. PMID- 8363539 TI - The concepts of selfobject function and empathy in couples therapy. AB - A model is advanced for couples therapy that uses a dyadic approach in which the partners bring about change in themselves as well as in the other by learning to tolerate and support that change. The model utilises concepts of selfobject function and empathic interaction between the partners; these are taken from Kohut's theory of human development. PMID- 8363540 TI - Structural characteristics of Australasian psychiatric practice. AB - A questionnaire examining structural and basic process characteristics of psychiatric practice was prepared by the RANZCP Quality Assurance Committee and circulated to all Fellows of the College in 1991. There were 830 replies (48%). A one in two sample of the replies was analysed and forms the basis of the descriptive report presented in this paper. PMID- 8363541 TI - Supervision in the training of a psychiatrist. AB - Supervision is the cornerstone of psychiatric training and yet receives scant attention either in the psychiatric literature or in training institutions. It is frequently a focus of ambivalence for those involved. This paper discusses the functions of supervision and the roles of the supervisor in the belief that attention to these issues will help resolve a number of ambiguities that exist in the supervisory relationship. PMID- 8363542 TI - Peer review of psychotherapeutic treatments in psychiatry: a review of the literature. AB - This paper reviews the literature concerning the current status of peer review of psychotherapeutic treatments in psychiatry. Accounts of the aims and mechanisms of peer review, administrative issues and the effects of peer review on patient care and professional practice are examined. PMID- 8363543 TI - The psychiatrist and peer review: a psychodynamic perspective. AB - Consideration of peer review is timely, given that formalization of peer review processes is one of the responses the psychiatric profession could make to increasing calls for accountability from within and without the profession. The establishment of formal peer review evoked strong, often hostile, responses among psychiatrists in the United States, reflecting considerable underlying anxiety. This paper examines the responses to formal peer review in psychiatrists from a psychodynamic perspective. PMID- 8363544 TI - Assault on staff in psychiatric hospitals: a safety issue. AB - All reported injuries between 1985 and 1987 in a large Queensland psychiatric hospital were studied. There were 650 incidents investigated; travelling injuries and injuries sustained by staff members not involved with patient care were excluded. Forty-eight per cent (n = 323) were assault based injury. Student nurses were most frequently assaulted. It was concluded that training in aggression management should include both counselling and self defence techniques, and that patient and staff rights should be balanced. Student nurses should have experience in wards with a low injury rate, prior to being rostered to the high risk wards. PMID- 8363545 TI - Sexual misconduct: is censure enough? AB - Although sexual relationships between medical practitioners and their patients have been forbidden by most professional and statutory bodies, the reported prevalence of sexual misconduct does not appear to have altered in the last 20 years. A recent Australian study has also suggested that psychiatrists are over represented in comparison to others in the medical workforce. The reasons that may account for this finding are discussed, and issues which require further debate by the profession are outlined. These include the acceptability of post termination relationships, the applicability of criminal statutes, the role of treatment in the management of offenders, and whether mandatory reporting of sexual misconduct should be considered. PMID- 8363546 TI - Inquiries at Lakeside and Aradale Hospitals: lessons and advances? AB - The release of reports of inquiries into two related psychiatric hospitals (Lakeside and Aradale) in Victoria occurred in 1991. These inquiries identified deficiencies in patient care standards and organisational dynamics. Knowledge of institutional dysfunction was available from similar Australian and overseas inquiries but nonetheless this knowledge had not prevented organisational inertia and decline in these two psychiatric hospitals. This paper examines the possible contribution of a failed medical hegemony model to organisational dysfunction and discusses organisational life-cycles. It reaches the conclusions that politically motivated inquiries do not achieve long term positive outcomes and that there is a need for academic research into the organisation of psychiatric services and staff productivity and morale. PMID- 8363547 TI - Promoting non-drug therapies. PMID- 8363548 TI - On combining TCAs and MAOIs. PMID- 8363549 TI - Efficacy of dynamic psychotherapy. PMID- 8363550 TI - The neglect of prevention in psychiatry. PMID- 8363551 TI - Fluoxetine-tricyclic combinations. PMID- 8363552 TI - Evaluation of psychotherapy. PMID- 8363553 TI - Polymorphism of transferrin found in the laboratory rat and wild rats in Japan. AB - Polymorphism of the transferrin locus (Tf) was found in the laboratory rat and wild rats in Japan by polyacrylamide gel electrophoresis. Two phenotypes, "a" and "b," were distinguished in homozygotes. It is suggested that these are controlled by autosomal codominant alleles. In 10 laboratory strains, only the IS strain showed the a type. This allele found in the IS strain was broadly distributed in Japanese wild rats. It is considered to be derived from a wild rat in Japan. Linkage relationship between Tf and Alp-1 was not established. PMID- 8363554 TI - The Gus-e locus regulates estrogen repression of androgen-induced beta glucuronidase expression in mouse kidney. AB - Both enzyme activity and mRNA concentration of beta-glucuronidase were measured in kidneys of mice treated with testosterone and the synthetic estrogen, diethylstilbestrol. Six congenic strains, all having a C57BL6/J genetic background but each having a different haplotype of the beta-glucuronidase gene complex, were compared. In each strain the induction caused by androgen was partially repressed by estrogen. The extent of this antagonism varied among the six haplotypes and was not coordinate with the extent of induction by androgen alone. Antagonism appears to be regulated by at least two alleles of a new locus, Gus-e, within the beta-glucuronidase gene complex. Repression by estrogen, like induction by androgen, appears to take place primarily at the transcriptional level. Kinetic studies revealed that estrogen causes the androgen response curve to plateau earlier and at a lower level. This suggests that estrogen increases the rate of gene deactivation rather than decreasing the rate of gene activation. Isoelectric focusing of beta-glucuronidase from Gus-ea and Gus-eb mice and their F1 progeny revealed that the genes are regulated in cis. Together, these findings support a model in which both sex hormones exert their effects on separate DNA response elements located in close proximity to the gene or within the gene itself. PMID- 8363555 TI - Malate dehydrogenase (MDH; EC 1.1.1.37) isozymes in tissues and callus cultures of Cereus peruvianus (Cactaceae). AB - Malate dehydrogenase (MDH; EC 1.1.1.37) isozymes were investigated in seeds and in seedlings and calli cultures of C. peruvianus to determine if the changes in MDH isozyme banding patterns could be used as biochemical markers to identify the origin of regenerated plants from callus tissues. Four cytoplasmic MDH isozymes (sMDH), five mitochondrial MDH isozymes (mMDH), and one glyoxysomal MDH isozyme (gMDH) were detected and showed tissue- and stage-specific expression. A relationship of mMDH and gMDH isozyme patterns with callus tissues subcultured in three hormonal combinations and with the plants regenerated from these callus tissues was demonstrated. Furthermore, temperature and mechanical stress were found to be closely related to mMDH-1 activity in callus culture. Therefore, the different patterns of MDH isozymes in the various tissues of C. peruvianus can be used as biochemical markers for the study of gene expression during development and as powerful tools in monitoring studies on callus cultures. PMID- 8363556 TI - Genetic mapping and protein product diversity of the self-incompatibility locus in wild tomato (Lycopersicon peruvianum). AB - Phenotypic diversity of self-incompatibility (S) alleles within nine natural populations of Lycopersicon peruvianum was investigated. Only 7 incompatible responses were observed of a total of 276 unique combinations tested, on the basis of controlled pollinations, indicating the large number of alleles that exist within these populations. Molecular weight polymorphism for specific major stylar proteins observed on SDS-PAGE was also evident in two of the populations examined. Five proteins were shown to map to the S locus and to be associated with different S alleles through controlled pollinations and segregation of the proteins. Two of these S related proteins had been described previously in terms of spatial and temporal expression consistent with their involvement in self incompatibility (Mau et al., Planta 169, 184-191, 1986). A mapping population derived from a fully compatible cross was used to establish linkage of the S locus to two DNA markers, CD15 and TG184, that lie on chromosome 1. The order of the markers and estimates of map distances are given. PMID- 8363557 TI - A comparison of genetic variation in two sibling species pairs of haplodiploid insects. AB - Sibling species pairs of sweat bees (Halictus confusus and H. tumulorum) and pine sawflies (Neodiprion pratti and N. maurus) were surveyed for genetic variability using enzyme electrophoresis. Levels of heterozygosity were found to be within the ranges earlier recorded for Hymenoptera. Expected heterozygosities were not significantly higher in the sawflies than in the sweat bees. Estimates of genetic identity between the sibling species were not lower than those generally found for diplodiploid insect species: no evidence was found for an increased rate of evolution in these haplodiploids. Genetic identity data among populations of H. confusus and between Halictus species were within the range expected for conspecific populations and sibling species, respectively. In Neodiprion all genetic distances were low but the two populations of N. pratti had similar genetic distances as each did to N. maurus, indicating the necessity for further systematic studies of the genus. PMID- 8363558 TI - Localization in the fourth linkage group of a gene di affecting diabetes insipidus in rats. AB - The diabetes insipidus gene has been localized in the fourth linkage group at a distance of 23.1 +/- 1.9 cM from the nonagouti loci and 29.5 +/- 2.1 cM from the Svp-1 loci based on the backcross progeny analysis of rats Rattus norvegicus mating (August x Brattleboro) F1 x Brattleboro. The proposed gene order is Svp-1- a--di. PMID- 8363560 TI - Tamoxifen decreases the rate of proliferation of rat vascular smooth-muscle cells in culture by inducing production of transforming growth factor beta. AB - Tamoxifen selectively and reversibly decreased the rate of proliferation of adult rat aortic vascular smooth-muscle cells (VSMCs). Half-maximal inhibition of proliferation occurred at 2-5 microM tamoxifen for VSMCs and at > 50 microM for adventitial fibroblasts. The cell cycle time for all the VSMCs in the population was increased from 35 +/- 2 h to 54 +/- 4 h in the presence of 33 microM tamoxifen. Tamoxifen did not affect the time of entry into DNA synthesis, but delayed arrival at mitosis by > 24 h. It therefore extended the duration of the G2-to-M phase of the cell cycle. However, the rate of proliferation of VSMCs was not decreased by tamoxifen (at concentrations up to 50 microM) in the presence of neutralizing antibody to transforming growth factor beta (TGF-beta). The level of mRNA for TGF-beta 1 in VSMCs was strongly induced by 10 microM tamoxifen, and TGF beta activity in conditioned medium from tamoxifen-treated cells was more than 50 fold higher than from control cells. Tamoxifen therefore extended the G2-to-M phase of the cell cycle in VSMCs by increasing TGF-beta activity in the culture. PMID- 8363561 TI - The activation of the arginine-citrulline cycle in macrophages from the spontaneously diabetic BB rat. AB - The activity of the arginine-citrulline cycle was investigated in macrophages from the spontaneous immunologically mediated diabetic BB rat. Peritoneal macrophages were prepared from male diabetes-prone (BBdp), diabetic (BBd) and age matched non-diabetes-prone (BBn) rats. Cells were incubated at 37 degrees C for 2 h in Krebs-Henseleit bicarbonate buffer containing 0.5 mM L-arginine, 0.1 mM L [ureido-14C]citrulline and 5 mM D-glucose to measure the activity of the arginine citrulline cycle. The uptakes of citrulline and arginine by macrophages were measured during a 5 min incubation period with L-[ureido-14C]citrulline and L [2,3-3H] arginine respectively. The production of NO3- (the major stable oxidation product of NO) increased (P < 0.01) by 112% and 151% in 75-day-old BBdp and 115-day-old BBd macrophages respectively, compared with age-matched BBn cells. The conversion of [14C]citrulline into [14C]arginine increased (P < 0.01) by 704%, 892% and 904% in 50- and 75-day-old BBdp and 115-day-old BBd macrophages respectively, compared with age-matched BBn cells. The enhanced NO synthesis in BBdp and BBd macrophages was associated with a 25-35% increase in the uptake of L arginine. However, there were no differences in the uptake of citrulline between BBdp or BBd macrophages and age-matched BBn cells. Our results demonstrate for the first time the activation of the arginine-citrulline cycle in macrophages in an autoimmune condition. The inherent increase in the recycling of L-citrulline to L-arginine in BBdp and BBd macrophages may reflect an innate metabolic disorder in these cells. This increased L-arginine synthesis from L-citrulline may play a role in sustaining a sufficient intracellular L-arginine concentration for prolonged generation of NO in BBdp and BBd macrophages. A role for NO in the autoimmune destruction of pancreatic beta-cells in insulin-dependent diabetes mellitus warrants further investigation. PMID- 8363562 TI - Ca2+ release from platelet intracellular stores by thapsigargin and 2,5-di-(t butyl)-1,4-benzohydroquinone: relationship to Ca2+ pools and relevance in platelet activation. AB - The effects of the Ca(2+)-ATPase inhibitors thapsigargin (Tg) and 2,5-di-(t butyl)-1,4-benzohydroquinone (tBuBHQ) were examined by using Ca(2+)-regulatory systems of platelet mixed membranes, saponin-permeabilized and intact platelets. Both agents inhibit Ca(2+)-ATPase activities of platelet mixed membranes, without any effect on the basal Mg(2+)-ATPase activity. Tg is more effective (EC50 = 35 nM) than tBuBHQ (EC50 = 580 nM). The effect of the two inhibitors on 45Ca2+ release from saponin-permeabilized platelets has also been characterized. 45Ca2+ uptake into non-mitochondrial intracellular stores occurs via an ATP-dependent mechanism, and if added at equilibrium the second messenger Ins(1,4,5)P3 releases 50% of the accumulated 45Ca2+. Maximally effective concentrations of Tg (1 microM) and tBuBHQ (50 microM) release 77% and 68% of the accumulated 45Ca2+. Addition of Ins(1,4,5)P3 together with either Tg or tBuBHQ resulted in a non additive release which was the same as with either Tg or tBuBHQ alone, indicating that the Ins(1,4,5)P3-sensitive Ca2+ pool was a subset of the pool that is sensitive to the Ca(2+)-ATPase inhibitors. Release of 45Ca2+ by either Tg or tBuBHQ was not affected by heparin, which totally blocked Ins(1,4,5)P3-induced Ca2+ release, and Tg was found not to affect [32P]Ins(1,4,5)P3 binding to its receptor on mixed membranes. Thus both Tg and tBuBHQ release Ca2+ from a pool that totally overlaps the Ins(1,4,5)P3-sensitive pool without affecting Ins(1,4,5)P3 function. In intact indomethacin-treated Fura 2-loaded platelets, Tg and tBuBHQ cause Ca2+ elevation, arising from release from intracellular stores and influx from the outside. Both Tg and tBuBHQ elevated Ca2+ to similar levels, which were less and slower than those observed with thrombin. Addition of thrombin to cells already treated with Tg or tBuBHQ produced further elevation of Ca2+, indicating agonist utilization of a Ca(2+)-ATPase inhibitor-insensitive pool. In aggregation experiments Tg and tBuBHQ showed different functional effects. In indomethacin-treated cells Tg induces slow aggregation and secretion responses, whereas tBuBHQ only induces shape change. Both agents show synergistic secretory responses with the protein kinase C activator dioctanoylglycerol (DiC8). Tg also showed greater ability than tBuBHQ to release [3H]arachidonic acid (AA) from [3H]AA-labelled platelets. Additionally, in [32P]Pi-labelled platelets both Tg and tBuBHQ induced phosphorylation of myosin light chain, a 27 kDa protein and the 45 kDa protein pleckstrin, but Tg showed a greater ability than tBuBHQ to cause phosphorylation of pleckstrin. These studies indicate that Tg and tBuBHQ are effective in releasing the Ins(1,4,5)P3-sensitive Ca2+ pool in platelets.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8363563 TI - Biochemical and immunological characterization of multiple glycoforms of mouse mast cell protease 1: comparison with an isolated murine serosal mast cell protease (MMCP-4). AB - Five highly soluble, chymotrypsin-like, neutral serine proteases, with molecular masses in the range 30-33 kDa, were isolated from Trichinella spiralis-infected mouse small intestine. These enzymes were closely related antigenically on Western blotting and by Ouchterlony double diffusion using a polyclonal, cross absorbed, sheep antibody raised against mouse mast cell protease-1 (MMCP-1) and on the basis of N-terminal amino acid sequence analysis, were identified as variant forms of MMCP-1. Substrate and inhibitor analysis confirmed that the five variants (MMCP-1 A-E) had similar characteristics, although highly significant (P = 0.025 to P < 0.0001) variations in Km and kcat, were detected. Against human alpha 1-proteinase inhibitor the Ki for MMCP-1C (45 pM) was significantly (P < 0.0001) greater than those for the other proteases (0.76-2.2 pM). The differences in electrophoretic mobility are probably a result of variable glycosylation, since removal of N-linked carbohydrate produced a polypeptide of approx. 28 kDa in each case which was, like the native enzyme, immunoreactive on Western blotting. A much less soluble 28 kDa enzyme was isolated from serosal mast cells and identified as MMCP-4 by N-terminal amino acid sequencing. Like MMCP-1 it has chymotrypsin-like substrate specificities with activity at neutral pH. However, it was antigenically distinct from MMCP-1 and, using sheep anti-MMCP-1, was not detected on Western blotting or by Ouchterlony double diffusion, e.l.i.s.a. or immunohistochemistry. This last technique established that the MMCP-1 variants were uniquely present in enteric mast cells, thereby providing a highly selective means of distinguishing the mucosal and connective tissue mast cell subsets in the mouse. PMID- 8363559 TI - Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. PMID- 8363565 TI - Identification of the putative hexose-phosphate translocator of amyloplasts from cauliflower buds. AB - Starch synthesis in amyloplasts isolated from cauliflower buds is strongly inhibited by the addition of micromolar concentrations of 4,4'-di-isothiocyano 2,2'-stilbenedisulphonic acid (DIDS). Using [3H]DIDS it was possible to label specifically a 31.6 kDa membrane protein of the envelope fraction of isolated amyloplasts. The intensity of the radioactive label was decreased in the presence of glucose 6-phosphate or dihydroxyacetone phosphate, indicating that this protein might be the amyloplastic hexosephosphate translocator. PMID- 8363564 TI - Differences in expression of transcription factor AP-1 in human promyelocytic HL 60 cells during differentiation towards macrophages versus granulocytes. AB - Commitment of HL-60 cells to macrophage or granulocytic differentiation was achieved by incubation with 4 beta-phorbol 12-myristate 13-acetate (PMA) for 30 60 min or with dimethyl sulphoxide (DMSO) for 24 h respectively. The commitment stage towards PMA-induced macrophage differentiation was associated with increases in jun B and c-fos mRNA levels, as well as with an increase in the binding activity of transcription factor AP-1. Nevertheless, gel retardation analysis indicated that the AP-1 activity detected in untreated cells was drastically reduced during the commitment stage of DMSO-induced HL-60 differentiation towards granulocytes. When HL-60 cells were treated with sodium butyrate, which induced monocytic differentiation, a remarkable increase in AP-1 binding activity was detected. Treatment of HL-60 cells with 1 alpha,25 dihydroxyvitamin D3, another monocytic differentiation agent, induced a weak, but appreciable, increase in AP-1 activity. Furthermore, addition of sodium butyrate or 1 alpha,25-dihydroxyvitamin D3 to HL-60 cells induced the expression of c-fos, c-jun, jun B and jun D proto-oncogenes. In contrast, when HL-60 cells were treated with retinoic acid, a granulocytic differentiation inducer, no enhanced AP-1 binding activity was observed, and only a weak increase in jun D mRNA level was detected. These data indicate that formation of AP-1 is not required for the induction of HL-60 differentiation towards granulocytes, whereas induction of monocytic differentiation is correlated with an increase in AP-1 activity. The differential expression of AP-1 activity may be critical in the differentiation of HL-60 cells towards monocytic or granulocytic lineages. PMID- 8363566 TI - Endothelin (ETA) receptor number and calcium signalling are up-regulated by protein kinase C-beta 1 overexpression. AB - To evaluate the role of protein kinase C (PKC) in regulation of cellular responsiveness to mitogens, we used rat 6 (R6) fibroblasts that stably overexpress the beta 1 isoenzyme of protein kinase C (PKC-beta 1). The potent vasoconstrictor and mitogen endothelin-1 (ET-1; 100 nM) was substantially more effective in stimulating InsP3 accumulation in PKC-beta 1-overexpressing fibroblasts (PKC3 cells) than in control fibroblasts lacking the PKC-beta 1 cDNA insert. PKC3 cells were found to express a 7-fold greater number of endothelin receptors than did control cells, whereas both cell lines showed equivalent Kd values. These receptors were of the ETA subtype, as defined by a 1000-fold greater affinity for ET-1 than for ET-3. Changes in intracellular free Ca2+ levels ([Ca2+]i) in response to ET-1 measured with the fluorescent Ca2+ indicator fura-2 showed that ET-1 was more potent and efficacious in stimulating [Ca2+]i in PKC3 cells than in control fibroblasts. The ET-1-induced Ca2+ rise was completely blocked by the selective ETA antagonist BQ123, but only slightly diminished by extracellular application of 2 mM EGTA. In contrast with the effects of PKC-beta 1 overexpression on responsiveness to ET-1, alpha-thrombin, which was previously found to have a weaker effect on InsP3 accumulation in PKC-beta 1-overexpressing cells, was also a less effective stimulator of [Ca2+]i in PKC3 cells than in control cells. These results demonstrate that, although the Ca2+ response to alpha-thrombin is diminished by PKC-beta 1 overexpression, ETA receptor number and cellular responsiveness to ET-1 are increased in PKC-beta 1-overexpressing cells. PMID- 8363568 TI - Restoration in vitro of normal rates of very-low-density lipoprotein triacylglycerol and apoprotein B secretion in hepatocyte cultures from diabetic rats. AB - Hepatocytes derived from diabetic rats were cultured in serum-free Waymouth's medium containing various supplements, after an initial 4 h period during which the cells were allowed to attach to the culture dish in the presence of foetal bovine serum (10%). After removal of serum, these cells secreted much less very low-density lipoprotein (VLDL) apoprotein B (apoB) and triacylglycerol than those derived from normal rats when cultured for 24 h in the basal medium. Inclusion of oleate (0.75 mM) in the medium initially increased the output of apoB and triacylglycerol, but the rates remained lower than those observed in normal hepatocytes and declined to zero after 72 h. This time-dependent decline in VLDL output was prevented by addition of dexamethasone to the oleate-containing medium. Levels of apoB and triacylglycerol output characteristic of normal hepatocytes could only be completely restored, however, by further addition of a mixture of lipogenic substrates (lactate plus pyruvate) to the medium. Restoration of normal levels of VLDL secretion in diabetic hepatocytes in vitro by this means was accompanied by a normal inhibitory response of apoB and triacylglycerol output to short-term (24 h) treatment with insulin or glucagon. Exposure of the cells to insulin for 72 h enhanced the secretion of VLDL, whereas treatment with glucagon for the same period potentiated the original inhibitory effect. The defective secretion of VLDL apoB observed when diabetic hepatocytes were cultured in the basal medium for 24 h could also be rectified by inclusion of a mixture of oleate (0.75 mM), lactate (10 mM), pyruvate (1 mM), dexamethasone (1 microM) and insulin (78 nM) in the medium during the 4 h attachment period in the presence of serum. Under these conditions, the increase in the secretory response of triacylglycerol was not so pronounced. PMID- 8363567 TI - Sex-dependent expression and growth hormone regulation of class alpha and class mu glutathione S-transferase mRNAs in adult rat liver. AB - The sex-dependent expression and growth hormone (GH) regulation of rat liver glutathione S-transferase (GST) was examined using oligonucleotide probes that distinguish between closely related class Alpha (Ya1, Ya2, Yc) and class Mu (Yb1, Yb2, Yb3) GST mRNAs [Waxman, Sundseth, Srivastava and Lapenson (1992) Cancer Res. 52, 5797-5802]. Northern-blot analysis revealed that the steady-state levels of GST Ya1, Yb1 and Yb2 mRNAs are 2.5-3-fold higher in male as compared with female rat liver. In contrast, GST Yc and Ya2 mRNAs were expressed at a 2-3-fold higher level in female rat liver. Microsomal GST mRNA did not exhibit significant sex dependent differences in rat liver. Treatment of male rats with GH by continuous infusion suppressed expression of the male-dominant GST Ya1, Yb1 and Yb2 mRNAs to levels at or below those found in female rat liver. This suppressive effect of GH was liver-specific, insofar as GH treatment did not alter kidney GST Ya1 mRNA levels. Hypophysectomy increased expression of the male-dominant GSTs, particularly in female rats (e.g. 8-fold elevation of GST Ya1 mRNA). GST Yc mRNA was increased approx. 2-fold in hypophysectomized males, indicating that this mRNA is subject to negative regulation by one or more pituitary-dependent factors. Continuous GH treatment of the hypophysectomized rats suppressed the expression of mRNA of GSTs Ya1, Yb1 and Yb2 when given as a continuous infusion, but not when given by an intermittent (twice daily) GH-injection schedule. Combination of continuous exposure to GH with thyroxine treatment resulted in a more complete suppression of GSTs Ya1, Yb1 and Yb2. In contrast, thyroxine increased the expression of GST Yc in hypophysectomized rats. These studies establish that several Alpha and Mu class GSTs are expressed in a sex-dependent fashion in adult rat liver, where they are regulated by multiple pituitary dependent hormones through pretranslational mechanisms. PMID- 8363569 TI - Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs. AB - PCR was used to demonstrate the presence of a conserved region and to clone novel members of the cytochrome P-450 4A gene family from guinea pig, human and mouse cDNAs. This strategy is based on the sequences at nucleotides 925-959 and at the haem binding domain (nucleotides 1381-1410) of the rat CYP4A1 gene. Murine Cyp4a clones showed high sequence identity with members of the rat gene family, but CYP4A clones from human and guinea pig were equally similar to the rat/mouse genes, suggesting that the rat/mouse line had undergone gene duplication events after divergence from human and guinea-pig lines. The mouse Cyp4a-12 clone was localized to chromosome 4 using interspecific backcross mapping, in a region of synteny with human chromosome 1. The assignment of the human CYP4A11 gene to chromosome 1 was confirmed by somatic cell hybridization. An RNAase protection assay was shown to discriminate between the murine Cyp4a-10 and Cyp4a-12 cDNAs. Treatment of mice with the potent peroxisome proliferator methylclofenapate (25 mg/kg) induced Cyp4a-10 RNA in liver, and to a lesser extent in kidney; there was no sex difference in this response. Cyp4a-12 RNA was present at high levels in male control liver and kidney samples, and was not induced by treatment with methylclofenapate. However, Cyp4a-12 RNA was present at low levels in control female liver and kidney RNA, and was greatly induced in both organs by methylclofenapate. Guinea pigs were exposed to methylclofenapate (50 mg/kg), but there was no significant induction of the guinea-pig CYP4A13 RNA. These findings are consistent with a species difference in response to peroxisome proliferators between the rat/mouse and the guinea pig. PMID- 8363570 TI - Detection, isolation and characterization of multiple lectins from the haemolymph of the cockroach Blaberus discoidalis. AB - Three agglutinins (lectins), designated BDL1, BDL2 and BDL3, were identified in the haemolymph of the cockroach Blaberus discoidalis by erythrocyte cross adsorption and sugar inhibition tests. With the use of (NH4)2SO4 fractionation, anion-exchange and affinity chromatography, BDL1 and BDL2 have been purified to homogeneity, and BDL3 has been partially purified to three bands on SDS/PAGE. BDL1 has a molecular-mass estimate of 390 kDa by gel filtration and approx. 158 kDa by SDS/PAGE under non-reducing conditions, further reduced to subunits of 36 kDa under reducing conditions. BDL2 has a molecular mass of approx. 140 kDa and is composed of subunits of 67 kDa which can be further reduced to identical subunits of 23 kDa. Isoelectric focusing in agarose gels revealed that BDL1 and BDL2 both focused as single bands at pH 6.0 and pH 5.2 respectively. The purified forms of BDL1 and BDL2 were stained by the periodic acid/Schiff's reagent showing that both lectins are glycoproteins. In addition, BDL1 was deglycosylated by endo beta-N-acetylglucosaminidase H. Immunological tests showed that these three lectins are not structurally related. All three lectins bind galactose but have different specificities for binding other sugars and for a range of vertebrate erythrocytes. BDL1 is specifically inhibited by D-(+)-glucose, D-(+)-mannose and N-acetyl-D-mannosamine, but not by N-acetyl-D-glucosamine, and BDL2 is inhibited by N-acetyl-D-glucosamine, but not by D-(+)-glucose, D-(+)-mannose or N-acetyl-D mannosamine. BDL3 is strongly inhibited by N-acetyl-D-galactosamine, but not by any of the other above-mentioned sugars. Erythrocyte specificities showed that BDL1 is more specific for rabbit than mouse erythrocytes, whereas BDL2 and BDL3 are more specific for mouse than rabbit erythrocytes. The haemagglutinating activities of both the serum and isolated lectins are Ca(2+)-dependent. Localization of BDL1 and BDL2 with fluorescein isothiocyanate-labelled antibodies showed that both lectins are associated with the granules and other areas of the cytoplasm of all blood cell types. PMID- 8363573 TI - The kinetics of slow-binding and slow, tight-binding inhibition: the effects of substrate depletion. AB - Inhibitors with dissociation constants in the micromolar to nanomolar range are important, but hard to characterize kinetically, especially when the substrate concentration in the assay is less than Km. When inhibition increases during the course of the assay (slow-binding inhibition) the concentration of substrate may decrease appreciably. Methods that take substrate depletion into account are described for analysing experiments in which the initial substrate concentration is below Km. Fitting progress curves gives the rate constants for the second (slow) step in a two-step mechanism. An approximate value for the overall dissociation constant may be determined from measurements of rates when the reaction is treated as a first-order process. When the concentrations of inhibitor and enzyme are comparable numerical methods are required. Procedures, suitable for implementation on a microcomputer, for the solution of the differential equations and the fitting of progress curves are described. PMID- 8363571 TI - An insulin receptor peptide (1135-1156) stimulates guanosine 5'-[gamma thio]triphosphate binding to the 67 kDa G-protein associated with the insulin receptor. AB - Peptides representing two putative G-protein-binding motifs (GPBP1 and GPBP2) derived from insulin-receptor sequences were tested for their ability to stimulate guanosine 5'-[gamma-thio]-triphosphate (GTP[S]; 'GTP gamma S') binding to a preparation containing the 41 and 67 kDa G-proteins that are associated with the insulin receptor [Jo, Cha, Davis and McDonald (1992) Endocrinology (Baltimore) 131, 2855-2861]. GPBP2 (residues 1135-1156) specifically stimulated GTP[S] binding, whereas GPBP1 (1319-1333) did not. Substitution of Arg-1152 with Gln in GPBP2 corresponding to a mutation site in insulin-resistant patients [Cocozza, Porcellini, Riccardi, Monticelli, Condorelli, Ferrera, Pianese, Miele, Capaldo, Beguinot and Varrone (1992) Diabetes 41, 521-526] attenuated the stimulatory potency of GPBP2. Size-exclusion chromatography and studies with purified 67 kDa G-protein revealed that GPBP2 stimulated GTP[S] binding only to the 67 kDa G-protein. These studies provide evidence for a potential regulatory site for G-protein interaction with the insulin receptor in the tyrosine kinase domain. PMID- 8363572 TI - Stereoselectivity of Ins(1,3,4,5)P4 recognition sites: implications for the mechanism of the Ins(1,3,4,5)P4-induced Ca2+ mobilization. AB - Ins(1,3,4,5)P4 was able to mobilize the entire Ins(1,4,5)P3-sensitive intracellular Ca2+ store in saponin-permeabilized SH-SY5Y human neuroblastoma cells in a concentration-dependent manner, yielding an EC50 value of 2.05 +/- 0.45 microM, compared with 0.14 +/- 0.03 microM for Ins(1,4,5)P3. However, L Ins(1,3,4,5)P4 [= D-Ins(1,3,5,6)P4] failed to cause mobilization of intracellular Ca2+ at concentrations up to 100 microM. Binding studies using pig cerebellar membranes as a source of both Ins(1,4,5)P3/Ins(1,3,4,5)P4-specific binding sites have revealed a marked contrast in their stereospecificity requirements. Ins(1,4,5)P3-receptors from pig cerebella exhibited stringent stereospecificity, L-Ins(1,4,5)P3 and L-Ins(1,3,4,5)P4 were > 1000-fold weaker, whereas Ins(1,3,4,5)P4 (IC50 762 +/- 15 nM) was only about 40-fold weaker than D Ins(1,4,5)P3 (IC50 20.7 +/- 9.7 nM) at displacing specific [3H]Ins(1,4,5)P3 binding from an apparently homogeneous Ins(1,4,5)P3 receptor population. In contrast, the Ins(1,3,4,5)P4-binding site exhibited poor stereoselectivity. Ins(1,3,4,5)P4 produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding, with two-site analysis revealing KD values for high- and low-affinity sites of 2.1 +/- 0.5 nM and 918 +/- 161 nM respectively. L-Ins(1,3,4,5)P4 also produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding which was less than 10-fold weaker than with D-Ins(1,3,4,5)P4 (IC50 values for the high and low-affinity sites of 17.2 +/- 3.7 nM and 3010 +/- 542 nM respectively). Therefore, although L-Ins(1,3,4,5)P4 appears to be a high-affinity Ins(1,3,4,5)P4 binding-site ligand in pig cerebellum, it is a very weak agonist at the Ca(2+) mobilizing receptors of permeabilized SH-SY5Y cells. We suggest that the ability of D-Ins(1,3,4,5)P4 to access intracellular Ca2+ stores may derive from specific interaction with the Ins(1,4,5)P3- and not the Ins(1,3,4,5)P4-receptor population. PMID- 8363574 TI - A method for extracting rate constants from initial rates of stopped-flow kinetic data: application to a physiological electron-transfer reaction. AB - The most commonly used methods for analysis of stopped-flow kinetic data require performing a series of measurements in which one reactant is varied at concentrations significantly greater than the concentration of the other reactant. For enzyme-catalysed reactions this may not be possible, because the dissociation constants for the enzyme-substrate complex are often of the same order of magnitude as the high concentrations of enzyme that must frequently be used in stopped-flow studies. An alternative method of data analysis is presented which allows the determination of microscopic rate constants from initial rates of stopped-flow kinetic data in which substrate is varied in a range of concentrations approximately the same as the enzyme. This method also provides a simple and accurate method for determining k4, the rate of the reverse reaction. This method has been used to describe a physiological electron transfer reaction between a quinoprotein, methylamine dehydrogenase, and a copper protein, amicyanin. At 20 degrees C, the rate of the electron-transfer reaction from methylamine dehydrogenase to amicyanin was 24 s-1, and the dissociation constant for complex-formation was 1.9 microM. PMID- 8363575 TI - 13C-n.m.r. of the cyanylated apoflavodoxin and flavodoxin from Clostridium pasteurianum. AB - The thiol group of the flavodoxin from Clostridium pasteurianum has been cyanylated in a single step using [cyanato-13C]2-nitro-5-thiocyanatobenzoic acid. This chemical modification increases the dissociation constant of the apoflavodoxin-FMN complex 10-fold from 0.33 +/- 0.15 nM to 2.9 +/- 1.3 nM. The thiocyanate carbons of the cyanylated cysteine residue of apoflavodoxin and flavodoxin had chemical shift values of 114.7 and 112.3 p.p.m. respectively. From these chemical shifts we conclude that the binding of FMN by the cyanylated apoflavodoxin causes a decrease in the polarity and/or hydrogen bonding capacity of the environment of the thiocyanate group. We compare these results with those obtained from similar studies on the cyanylated apoflavodoxin and flavodoxin from Megasphaera elsdenii and we discuss how FMN binding and cyanylation perturb the structures of apoflavodoxins from Megasphaera elsdenii and Clostridium pasteurianum. PMID- 8363577 TI - Xyloglucan glucosyltransferase in Golgi membranes from Pisum sativum (pea). AB - Cell membranes from etiolated Pisum sativum (pea) tissues were separated by ultracentrifugation on linear sucrose density gradients and assayed for membrane marker and glycosyltransferase activity. Membrane fractions were shown to incorporate glucose from UDP-D-[14C]glucose into polysaccharides with glycosyl linkages consistent with synthesis of xyloglucan. A combined assay using g.c., radiogas proportional counting and m.s. was employed to determine the identities of 14C-labelled glycosyl residues and the glycosyl linkages between them. In glucan synthase I assays, membrane fractions enriched for Golgi membranes showed 14C incorporation into 4- and 4,6-glucose residues, with minor incorporation into 3-glucose residues. In glucan synthase II assays, all 14C incorporation was into 3- and 3,4-glucose. There was a shift in glycosyl linkage of 14C incorporation from predominantly 4-glucose at low UDP-glucose concentration to predominantly 3- and 3,4-glucose at high UDP-glucose concentrations. Mn2+ stimulated incorporation of radioactivity into 4,6-glucose residues characteristic of xyloglucan polysaccharides. Addition of exogenous UDP-xylose to assay mixtures stimulated incorporation into 4,6-glucose, with a maximum at 15 microM UDP-xylose. PMID- 8363576 TI - A putative glutathione-binding site in CdZn-metallothionein identified by equilibrium binding and molecular-modelling studies. AB - Glutathione (GSH) has been found to form a complex with both vertebrate and invertebrate copper-metallothionein (CuMT) [Freedman, Ciriolo and Peisach (1989) J. Biol. Chem. 264, 5598-5605; Brouwer and Brouwer-Hoexum (1991) Arch. Biochem. Biophys. 290, 207-213]. In this paper we report on the interaction of GSH with CdZnMT-I and CdZnMT-II from rabbit liver and with CdMT-I from Blue crab hepatopancreas. Ultrafiltration experiments showed that all three MTs combined with GSH. The measured binding data for the three MTs could be described by a single binding isotherm. The GSH/MT stoichiometry was 1.4 +/- 0.3 and Kdiss. = 14 +/- 6 microM. Partially Zn-depleted MT does not significantly bind GSH, indicating that the GSH-binding site is located on MT's Zn-containing N-terminal domain. The putative GSH-binding site on rabbit liver MT was investigated using molecular-graphics analysis. A cleft on the MT's N-terminal domain, which has the labile Zn-2 at its base, could easily accommodate GSH. Cysteine-ligand exchange between the terminal (non-bridging) Cys-26, bound to Zn-2, and the cysteine in GSH is stereochemically possible. Based on these considerations a model of MT-GSH was built in which GSH's cysteine replaces Cys-26 as a terminal Zn-2 ligand. This complex was energy-minimized by molecular-mechanics calculations, taking into account computed partial electrostatic charges on all atoms, including Cd and Zn. These calculations showed that the MT-GSH complex was thermodynamically more stable than MT, due to favourable non-bonded, electrostatic and van der Waals interactions. Six hydrogen bonds can form between GSH and MT. The average pairwise root-mean-square deviations (RMSD) of the metals in energy-minimized MT and MT-GSH, compared with the metals in the crystal structure, were 0.0087 +/- 0.0028 nm (0.087 +/- 0.028 A) and 0.0168 +/- 0.0087 nm (0.168 +/- 0.087 A) respectively. The RMSD values for the polypeptide-backbone alpha carbons were 0.0136 +/- 0.0060 nm (0.136 +/- 0.060 A) and 0.0491 +/- 0.0380 nm (0.491 +/- 0.380 A) respectively. No other docking sites for GSH were found. The energy minimized structure of an MT-2-mercaptoethanol complex was somewhat less stable than the native MT domain, attesting to the specificity of the MT-GSH interaction. The possible physiological significance of the MT-GSH interaction is discussed. PMID- 8363578 TI - Organization and sequences of genes for the subunits of ATP synthase in the thermophilic cyanobacterium Synechococcus 6716. AB - The sequences of the genes for the nine subunits of ATP synthase in the thermophilic cyanobacterium Synechococcus 6716 have been determined. The genes were identified by comparison of the encoded proteins with sequences of ATP synthase subunits in other species, and confirmed for subunits alpha, beta, delta and epsilon, by determining their N-terminal sequences. They are arranged at three separate loci. Six of them are in one cluster in the order a: c: b': b: delta: alpha, and those for the beta and epsilon subunits form a second and separate cluster. The gene for the gamma-subunit is at a third site. As in other bacteria, the gene for subunit a is immediately preceded by a gene coding for a small hydrophobic protein of unknown function, known as uncI in Escherichia coli. The gene orders in Synechococcus 6716 are related to the orders of ATP synthase genes in the plastid genomes of higher plants, and particularly of a red alga and a diatom. The sequences of the subunits are similar to those of chloroplast ATP synthase, the alpha, beta and c subunits being particularly well conserved. Differences in the primary structures of the Synechococcus 6716 and chloroplast gamma subunits probably underlie different mechanisms of activation of ATP synthase. The nucleotide sequences that are presented also contain 12 other open reading frames. One of them encodes a protein sequence related to the E. coli DNA repair enzyme, photolyase, and another codes for a protein that contains internal repeats related to sequences in the myosin heavy chain. PMID- 8363579 TI - Purification of a 100 kDa phospholipase A2 from spleen, lung and kidney: antiserum raised to pig spleen phospholipase A2 recognizes a similar form in bovine lung, kidney and platelets, and immunoprecipitates phospholipase A2 activity. AB - Phospholipase A2 (PLA2) plays a key role in the production of intracellular and extracellular chemical mediators such as arachidonic acid, eicosanoids and platelet-activating factor, which modulate membrane channel activity, signal transduction, are vasoactive and chemotactic, and are implicated in many pathophysiological mechanisms of inflammation and tissue injury. We previously identified, purified and characterized an arachidonic acid-selective cytosolic 100-110 kDa PLA2 from bovine platelets and rat kidney that is activated during cell stimulation. The purification schemes previously published resulted in low yields of enzyme, insufficient for extensive biochemical characterization. We report the purification of a large-molecular-mass (100 kDa) PLA2 from pig spleen, bovine kidney and bovine lung, using a novel large-scale purification scheme. The enzyme was purified to near homogeneity from an acidified extract obtained from 4.8 kg of pig spleen by sequential use of DEAE-cellulose anionic exchange, Butyl Toyopearl hydrophobic chromatography and DEAE-5PW h.p.l.c., and further purified by non-denaturing PAGE. This purification scheme will permit the preparation of quantities of purified native enzyme sufficient to study its properties and regulation. To generate antiserum against the PLA2 enzyme, the 100 kDa protein was excised and electroeluted from SDS/PAGE gels of the active fractions after DEAE-5PW h.p.l.c., and this was used as antigen. This polyclonal antibody against pig spleen 100 kDa PLA2 protein reacted with 100 kDa bands in preparations partially purified from bovine platelets, kidney and lung as well as pig spleen, and immunoprecipitated PLA2 activity from these sources. The antibody also immunoprecipitated a 100 kDa protein from cytosolic fractions of cultured renal mesangial cells, human erythroleukaemia cells and human monocytic U937 cells. Considerable PLA2 activity was present in the immunoprecipitates. To our knowledge this antibody is unique in its ability to permit measurement of PLA2 activity in the immunoprecipitate itself, and will be a useful tool for the study of the regulation and the activation mechanisms of the native PLA2 enzyme. PMID- 8363580 TI - Osteoblast-specific factor 2: cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I. AB - A cDNA library prepared from the mouse osteoblastic cell line MC3T3-E1 was screened for the presence of specifically expressed genes by employing a combined subtraction hybridization/differential screening approach. A cDNA was identified and sequenced which encodes a protein designated osteoblast-specific factor 2 (OSF-2) comprising 811 amino acids. OSF-2 has a typical signal sequence, followed by a cysteine-rich domain, a fourfold repeated domain and a C-terminal domain. The protein lacks a typical transmembrane region. The fourfold repeated domain of OSF-2 shows homology with the insect protein fasciclin I. RNA analyses revealed that OSF-2 is expressed in bone and to a lesser extent in lung, but not in other tissues. Mouse OSF-2 cDNA was subsequently used as a probe to clone the human counterpart. Mouse and human OSF-2 show a high amino acid sequence conservation except for the signal sequence and two regions in the C-terminal domain in which 'in-frame' insertions or deletions are observed, implying alternative splicing events. On the basis of the amino acid sequence homology with fasciclin I, we suggest that OSF-2 functions as a homophilic adhesion molecule in bone formation. PMID- 8363581 TI - Expression of transcripts for two interleukin 8 receptors in human phagocytes, lymphocytes and melanoma cells. AB - Two cDNAs coding for distinct interleukin 8 (IL-8) receptors, IL-8R1 [Murphy and Tiffany (1991) Science 253, 1280-1283] and IL-8R2 [Holmes, Lee, Kuang, Rice and Wood (1991) Science 253, 1278-1280] have been reported, and biochemical studies on human neutrophils have revealed two proteins (p70 and p44) that bind IL-8 with high affinity [Moser, Schumacher, von Tscharner, Clark-Lewis and Baggiolini (1991), J. Biol. Chem. 266, 10666-10671]. We have cloned the cDNA coding for IL 8R1 from a library of differentiated HL-60 cells. Transfection of this cDNA into Jurkat cells resulted in the expression of high-affinity binding for IL-8 and two related cytokines, GRO alpha and neutrophil-activating peptide 2 (Kd 0.5-1.0 nM). Northern-blot analysis with the IL-8R1 cDNA as probe revealed abundant expression of transcripts of different size in human neutrophils and low-level expression of a single RNA species in HL-60 cells differentiated with dimethyl sulphoxide and retinoic acid. Because of the extensive nucleotide sequence similarity of the cDNAs for IL-8R1 and IL-8R2, the reverse-transcription PCR method was used for analysis of RNA expression in myeloid and lymphoid cells, 19 cell lines established from human primary melanomas or metastases, two melanocyte and one fibroblast cell lines. IL-8R1 mRNA transcripts were expressed at high levels in neutrophils, and to a lesser extent in blood monocytes and the myeloid cell lines, HL-60 and AML 193, but were not found in THP-1 cells, lymphocytes and Jurkat cells. IL-8R2 mRNA transcripts, by contrast, were found in all blood cells and related cell lines, as well as in all melanoma, melanocyte and fibroblast cell lines tested. As for IL-8R1, IL-8R2 mRNA expression was highest in neutrophils. These results suggest that IL-8R1 and IL-8R2 may both be involved in neutrophil activation by IL-8 and related cytokines, and presumably correspond to p70 and p44, the receptors that were identified biochemically. Possible IL-8 functions on lymphocytes and melanoma cells, e.g. chemotaxis and proliferation, must be independent of IL-8R1 and may be mediated by IL-8R2. PMID- 8363582 TI - Abundant bacterial expression and reconstitution of an intrinsic membrane transport protein from bovine mitochondria. AB - The oxoglutarate carrier, an intrinsic membrane-transport protein of the inner membranes of bovine-heart mitochondria, has been expressed at an abundant level in Escherichia coli. It accumulates in the bacterium as inclusion bodies, and none of the protein was detected in the bacterial inner membrane. The mitochondrial ADP/ATP carrier, a member of the same super-family of transport proteins as the oxoglutarate carrier, has also been expressed in E. coli. However, the expression of the ADP/ATP carrier in bacteria retards their growth, and so the levels of expression that were attained were lower than those of the oxoglutarate carrier. The oxoglutarate carrier inclusion bodies have been disaggregated with the detergent N-dodecanoyl-sarcosine, and the protein has been incorporated into liposomes. In its ability to transport oxoglutarate and malate and other known substrates of the carrier in mitochondria, and in its inhibition characteristics by a wide range of non-competitive and competitive inhibitors, this reconstituted oxoglutarate carrier is similar to the natural protein in the inner membranes of mitochondria, and to the carrier that has been purified from mitochondria and reconstituted in liposomes. These experiments remove significant obstacles to crystallization trials and to site-directed mutagenesis of the oxoglutarate carrier. PMID- 8363583 TI - Effect of lead acetate and carbon particles on the expression of glutathione S transferase YfYf in rat liver. AB - Administration of intracardiac lead acetate produces a complex response in glutathione S-transferase (GST) YfYf expression in rat liver. The earliest response, an elevation of GST expression in Kupffer cells, can be mimicked by administering a suspension of carbon particles. The second effect of lead acetate administration is a marked elevation of GST YfYf in some but not all hepatocytes (the 'patchy' response). This effect is most marked 48-76 h after administration of a single dose of lead acetate and is easily detected by immunoblotting. Dexamethasone down-regulates the lead response in hepatocytes. PMID- 8363585 TI - Conformational properties of Bacillus subtilis RNA polymerase sigma A factor during transcription initiation. AB - By the use of a partial proteolysis method and Western-blot analysis, the conformational properties of Bacillus subtilis sigma A factor in the transcription initiation stage were studied. From a comparison of the trypsin digestion patterns of free sigma A and of sigma A associated with core enzyme, it was found that the production of 45 kDa sigma A tryptic-derived fragment was enhanced when sigma A was associated with the core enzyme. More importantly, a 40 kDa sigma A tryptic-derived fragment was found exclusively in this associated state. Based on the change of the digestion kinetics when producing the 45 kDa tryptic fragment and the generation of this new 40 kDa tryptic fragment from sigma A, it was apparent that a conformation change of sigma A occurred during the association of sigma A with the core enzyme. Also, similar patterns were found for the sigma A present in the holoenzyme-promoter DNA complex. These findings suggest that no further distinctive conformational change of sigma A occurs at the step of RNA polymerase holoenzyme and promoter DNA complex formation. Trypsin-digestion patterns of sigma A in different RNA polymerase holoenzyme and promoter DNA complexes were also studied. The presence of similar trypsin digestion-patterns of sigma A in those complexes strongly supports the idea that a similar sigma A conformation is used in the recognition of different sigma A-type promoters and the formation of different open complexes. PMID- 8363584 TI - Substrate-dependent changes in mitochondrial function, intracellular free calcium concentration and membrane channels in pancreatic beta-cells. AB - Microfluorimetric and patch-clamp techniques have been combined to determine the relationship between changes in mitochondrial metabolism, the activity of KATP channels and changes in intracellular free calcium concentration ([Ca2+]i) in isolated pancreatic beta-cells in response to glucose, ketoisocaproic acid (KIC) and the electron donor couple tetramethyl p-phenylenediamine (TMPD) and ascorbate. Exposure of cells to 20 mM glucose raised NAD(P)H autofluorescence after a delay of 28 +/- 1 s (mean +/- S.E.M., n = 30). The mitochondrial inner membrane potential, delta psi m (monitored using rhodamine 123 fluorescence), hyperpolarized with a latency of 49 +/- 6 s (n = 17), and the [Ca2+]i rose after 129 +/- 13 s (n = 5). The amplitudes of the metabolic changes were graded appropriately with glucose concentration over the range 2.5-20 mM. All variables responded to KIC with shorter latencies: NAD(P)H autofluorescence rose after a delay of 20 +/- 3 s (n = 5) and rhodamine 123 changed after 21 +/- 3 s (n = 6). The electron donor couple, TMPD with ascorbate, rapidly hyperpolarized delta psi m and raised [Ca2+]i. When [Ca2+]i was raised by sustained exposure to 20 mM glucose, TMPD had no further effect. TMPD also decreased whole-cell KATP currents and depolarized the cell membrane, measured with the perforated patch configuration. These data are consistent with a central role for mitochondrial oxidative phosphorylation in coupling changes in glucose concentration with the secretion of insulin. PMID- 8363586 TI - Inactivation of mouse liver glutathione S-transferase YfYf (Pi class) by ethacrynic acid and 5,5'-dithiobis-(2-nitrobenzoic acid). AB - Mouse liver glutathione S-transferase YfYf (Pi class) reacts with [14C]ethacrynic acid to form a covalent adduct with a stoichiometry of 1 mol per mol of subunit. Proteolytic digestion of the enzyme-[14C]ethacrynic acid adduct with V8 protease produced an 11 kDa fragment containing radioactivity. Sequencing revealed this to be an N-terminal peptide (minus the first 15 residues, terminating at Glu-112) which contains only one cysteine residue (Cys-47). This is tentatively identified as the site of ethacrynic attachment. Kinetic studies reveal that glutathione S conjugates protect against inactivation by ethacrynic acid, but the level of protection is not consistent with their potency as product inhibitors. A model is proposed in which glutathione S-conjugates and ethacrynic acid compete for the free enzyme, and a second molecule of ethacrynic acid reacts covalently with the enzyme-ethacrynic acid complex. The native protein contains one thiol reactive with 5,5'-dithiobis-(2-nitrobenzoic acid) at neutral pH. The resultant mixed disulphide, like the ethacrynic acid adduct, is inactive, but treatment with cyanide (which incorporates on a mol for mol basis) restores activity to 35% of that of the native enzyme. PMID- 8363587 TI - Disulphide cross-linking of smooth-muscle and non-muscle caldesmon to the C terminus of actin in reconstituted and native thin filaments. AB - It was reported that chicken gizzard smooth-muscle caldesmon Cys-580 can be disulphide-cross-linked to the C-terminal pen-ultimate residue (Cys-374) of actin, indicating that these residues are close in the protein complex [Graceffa, P. and Jancso, A. (1991) J. Biol. Chem. 266, 20305-20310]. Since the possibility that the cross-link involves a cysteine residue other than actin Cys-374 was not absolutely excluded, more direct evidence was sought for the identify of the cysteine residues involved in the cross-link. We show here that caldesmon could not be disulphide-cross-linked to actin which had Cys-374 removed by carboxypeptidase A digestion, providing direct support for the participation of actin Cys-374 in the cross-link to caldesmon. In order to assign the caldesmon cysteine residue involved in the cross-link, use was made of caldesmon from porcine stomach muscle, which is shown to contain one cysteine residue close to, or at, position 580, in contrast with chicken gizzard caldesmon, which has an additional cysteine residue at position 153. The porcine stomach caldesmon also formed a disulphide-cross-link to actin, further supporting the original conclusion that Cys-580 of the chicken gizzard caldesmon had been cross-linked to actin. Disulphide-cross-linking with similar yield was also observed in native chicken gizzard muscle thin filaments, indicating that the interaction between actin and the C-terminal domain of caldesmon is the same in native and reconstituted thin filaments. The much smaller non-muscle isoform of caldesmon, from rabbit liver, could be similarly cross-linked to actin, consistent with the sequence similarity between the C-terminal domain of muscle and non-muscle caldesmon. The ability to cross-link caldesmon Cys-580 to actin Cys-374 suggests the possibility that the Cys-580 region of caldesmon and the C-terminus of actin form part of the actin-caldesmon binding interface. PMID- 8363588 TI - High-level expression of soluble rat hsc70 in Escherichia coli: purification and characterization of the cloned enzyme. AB - We have cloned the cDNA of rat hsc70 (clathrin-uncoating ATPase) into a T7 expression system and have expressed this enzyme in Escherichia coli. The recombinant clathrin-uncoating ATPase is in the cytosolic fraction of the bacterium and is soluble. It was purified to homogeneity by DEAE-cellulose and ATP-agarose column chromatography. From 1 litre of bacterial culture (0.3-0.4 g of proteins), 5-20 mg of pure recombinant clathrin-uncoating ATPase was routinely obtained. The cloned enzyme is capable of dissociating clathrin from bovine coated vesicle. Furthermore, it is not methylated on basic amino acid residues and is not blocked at the N-terminus, indicating that these modifications on hsc70 are not essential for uncoating of clathrin. Binding of [alpha-32P]ATP by purified recombinant hsc70 was analysed by Scatchard plot. The results indicate that there one high-affinity binding component with a Kd (dissociation constant) of 0.2-0.3 microM. The peptide-stimulated ATPase activities of recombinant hsc70 at 37 degrees C with respect to S-peptide peptides P3a and GT4 at a concentration of 1.2 mM are 142 +/- 6, 214 +/- 8 and 362 +/- 5 pmol/h per micrograms of hsc70 protein respectively. The EC50 values of hsc70 ATPase for S-peptide, peptides P3a and GT4 are 2, 0.67 and 0.17 mM respectively. On the other hand, the dissociation constants of S-peptide, peptides P3a and GT4 for recombinant hsc70 are 7.6, 13 and 100 microM respectively. Thus peptide GT4 is the only peptide examined for which the binding constant is comparable with the EC50 for stimulation ATPase activity, albeit it has the lowest affinity for hsc70. PMID- 8363589 TI - Expression of precursor and mature carnitine palmitoyltransferase II in Escherichia coli and in vitro: differential behaviour of rat and human isoforms. AB - cDNAs corresponding to the precursor and mature forms of rat carnitine palmitoyltransferase II (CPT II) were found to be readily expressed in Escherichia coli. In both cases, catalytically active immunoreactive protein was produced and became largely membrane-associated. The precursor form of the enzyme was not proteolytically processed. Removal of 126 bp from the 5' end of the cDNA coding region allowed expression of a truncated CPT II (lacking the N-terminal 17 residues of the mature protein), but this product was inactive. cDNAs encoding the precursor and mature forms of human CPT II resisted direct expression in E. coli. However, the impediment was overcome when the latter cDNA was ligated in frame 3' to sequence encoding a glutathione S-transferase. This construct yielded abundant quantities of the corresponding fusion protein, a portion of which was soluble and catalytically active. In vitro transcription and translation of the various cDNAs established that the lower mobility on SDS/PAGE of rat CPT II compared with its human counterpart (despite their identical numbers of amino acids) is an intrinsic property of the primary sequences of the proteins themselves. Also, the human cDNA was found to contain an artifactual termination signal for T3 RNA polymerase that could be bypassed by the T7 polymerase. Thus rat CPT II can be expressed in active form in E. coli with characteristics similar to those of the enzyme in mitochondria, opening the way to future location of active sites within the molecule. An alternative expression system will be needed for similar studies on human CPT II. PMID- 8363590 TI - Control analysis applied to single enzymes: can an isolated enzyme have a unique rate-limiting step? AB - Control analysis is used to analyse and quantify the concept of a rate-limiting step within an enzyme. The extent to which each rate constant within the enzyme limits the steady-state rate of the enzyme and the levels of enzyme intermediate species are quantified as flux and concentration control coefficients. These coefficients are additive and obey summation theorems. The control coefficients of triose phosphate isomerase, carbamate kinase and lactate dehydrogenase are calculated from literature values of the rate constants. It is shown that, contrary to previous assumption, these enzymes do not have a unique rate-limiting step, but rather flux control is shared by several rate constants and varies with substrate, product and effector concentrations, and with the direction of the reaction. Thus the general assumption that an enzyme will have a unique rate limiting step is unjustified. PMID- 8363591 TI - Purinergic (P2) receptor-operated calcium entry into rat thyroid cells. AB - In the epithelial cell line FRT, derived from rat thyroid, extracellular ATP, at a concentration as low as 1 x 10(-7) M, specifically increases cytosolic Ca++ two fold over the basal level of 255 +/- 45 nM. A maximum increase of 5 fold over basal is seen at 1 x 10(-5) M ATP. The effect occurs in the absence of any measurable phosphatidyl inositol metabolism and requires the presence of extracellular Ca++, but is independent of extracellular Na+; it is duplicated by ATP gamma S but not by adenosine, AMP, ADP, AMP-PNP, AMP-CPP, or AMP-PCP. In the presence of the P2-receptor antagonist suramin, the ATP induced Ca++ influx is completely inhibited, whereas Mg++, La , and verapamil are ineffective. It appears that the most likely (and unique) mechanism of ATP induced increase of cytosolic Ca++ in FRT cells in an increased influx through the activation of a P2 receptor operated Ca++ channel. PMID- 8363592 TI - Identification of two human brain aryl sulfotransferase cDNAs. AB - A 1,179 bp and a 1,424 bp full-length aryl sulfotransferase cDNAs were isolated from a human brain cDNA library. Their coding domains are 93% identical, each encoding a cytosolic protein of 295 amino acids. Their deduced amino acid sequences of these cDNAs are also 93% identical. The 1179 bp brain cDNA has an identical coding domain to a previously reported human liver aryl sulfotransferase cDNA but it has a different 5' noncoding sequence. Northern blot analysis using a probe specific for the 1,424 bp cDNA identified a 1500 bp band in mRNA of human liver, colon, kidney and lung. In a human hepatocellular carcinoma the same band plus an extra larger band was also recognised. An intron of the gene encoding the 1424 bp cDNA was also identified. PMID- 8363593 TI - Nucleotide sequence of the rabbit gamma-preprotachykinin I cDNA. AB - We succeeded in amplifying tachykinin I specific cDNAs from cerebral tissue of guinea pig, rabbit, rat, hamster, trout and tupaia in the expected size range of 820-980 bp. The amplified 859 bp rabbit gamma-preprotachykinin I cDNA was sequenced and consisted of the whole 345 bp gamma-PPT I coding sequence including the substance P and neurokinin A coding regions and a 505 bp large 3' nontranslated region. Both, molecular weight and sequence comparison emphasizes the very high phylogenetic age of the preprotachykinin I gene. PMID- 8363594 TI - Annexins from bovine adrenal cortex exhibit specific cytosol/membrane solvation. AB - Cytosol/membrane localization of annexins I to VI was analyzed in tissue extracts from bovine adrenal cortex. Based on their solubility in either aqueous or detergents solutions, they were subfractionated in three groups named cytosolic (C), membrane-bound (MB) and membrane-inserted (MI). Less than 1% of the total annexins present in the tissue were recovered in the C fraction when as much as 76.5 and 22.5% were obtained respectively in the MB and the MI fractions. By immunoblotting after SDS-PAGE, it was shown that the various members of the annexin family were not equally recovered in the different fractions. A-V and A VI were found present in the three fractions whereas the distribution of A-I, A II, A-III and A-IV was distinct, suggesting different cellular functions. PMID- 8363595 TI - Inhibitory effect of arachidonic acid on GTPase activating protein is antagonized by 1-stearoyl, 2-arachidonoyl glycerol. AB - The intrinsic GTPase activity of cellular protein p21ras is strongly increased by cytosolic GTPase activating protein (GAP). The activity of this enzyme has been shown to be inhibited by arachidonic acid. We report here that this inhibition is antagonized by the presence of 1-stearoyl, 2-arachidonoyl glycerol. This effect is structure specific and dose dependent, being maximum at 200 micrograms/ml of diacylglycerol (DG). These results suggest that production of DG in response to hormones or growth factors stimulation could indirectly modulate the interaction between p21ras and GAP. PMID- 8363596 TI - Specific regulation of male rat liver cytosolic estrogen receptor by the modulator of the glucocorticoid receptor. AB - Modulator is a novel low-molecular-weight organic compound that regulates activities of glucocorticoid and mineralocorticoid receptors as well as protein kinase C. In this study we show that male rat liver cytosolic estrogen receptor activation is inhibited by modulator in a dose-dependent manner. Fifty percent inhibition is obtained with 1 unit/ml modulator purified from bovine liver which is within the physiological concentration for modulator. However, sheep uterine cytosolic estrogen and androgen receptors are insensitive to regulation by modulator. Exogenous sodium molybdate treatment inhibits activation of all of these receptors of liver or uterus origin in an identical manner, further differentiating the effects of modulator and the molybdate anion. PMID- 8363597 TI - Alteration of protein kinase C activity in diabetic rat prostate. AB - Protein kinase C activity is present in rat prostatic epithelial cells in both cytosolic and membrane subcellular fractions. Partial purification by ion exchange chromatography and characterization of cofactor requirements showed its behavior as a classical Ca(2+)- and phospholipid-dependent enzyme activated by 1,2-diacylglycerol (or by mimicking agents such as tumor-promoting phorbol esters). Streptozotocin-induced diabetes resulted in an increase of the membrane/cytosolic enzyme ratio suggesting a redistribution of protein kinase C from the cytosolic to the membrane fraction (an index of enzyme activation) that could be reversed toward control conditions by insulin treatment. Differences observed in cofactor requirements for maximal enzyme activation argue for a some distinct expression of protein kinase C isozymes in control and diabetic conditions. These results are a new aspect of the complex set of alterations exhibited by the diabetic prostate in the signal transduction mechanisms that mediate cell functions and proliferation in this gland which could be related to the prostate atrophy and impaired fertility characteristic of this disease. PMID- 8363598 TI - Unique preS sequence in a gibbon-derived hepatitis B virus variant. AB - A unique hepatitis B virus (HBV) variant has been identified in a gibbon (Hylobates lar) which could be passed to a chimpanzee by experimental inoculation. This HBV variant had been shown to have no reactivity to a monoclonal anti-preS2 antibody (preS2 mAb 116-34) differentiating it from all human HBV specimens tested. This gibbon sera also was not recognized by an anti preS1 mAb which binds the preS1 hepatocyte receptor region, amino acids 27-35. In this paper, we report the DNA sequence of the gibbon HBV PreS gene. The lack of preS2 mAb (116-34) binding can be explained by a unique nucleotide substitution of A for C in the second codon of the preS2 region leading to the replacement of glutamine with lysine. Two other unique changes were observed at the seventh and 24th amino acid positions in the preS2 gene leading to a substitution of a valine for threonine and alanine, respectively. Unlike all human derived HBV sequences in the preS1 region, the gibbon HBV had a glutamic acid instead of an aspartic acid at amino acid residue 27. Another unique substitution was a leucine for alanine at preS1 position 33. These amino acid changes in the gibbon HBV may explain its unique preS mAb reactivity. PMID- 8363599 TI - Inositol 1,4,5-trisphosphate-induced calcium release in permeabilized platelets is coupled to hydrolysis of inositol 1,4,5-trisphosphate to inositol 1,4 bisphosphate. AB - Metabolism of inositol 1,4,5-trisphosphate (IP3) and IP3-induced release of Ca2+ was analyzed in permeabilized human platelets. Both rapid Ca2+ release and hydrolysis of IP3 to inositol 1,4-bisphosphate (IP2) was observed after addition of IP3 to permeabilized, Ca(2+)-loaded platelets. In the absence of ATP or in the presence of inhibitors of the Ca(2+)-ATPase of the endoplasmic reticulum, no release of Ca2+ and little hydrolysis of IP3 occurs, indicating a coupling between the Ca2+ gradient across the membrane of the IP3-sensitive Ca2+ store and conversion of IP3 to IP2. In addition, the rapid recovery of the sensitivity of the IP3-sensitive Ca2+ store after successive additions of IP3 (increment detection) appears to be associated with hydrolysis of IP3. PMID- 8363600 TI - Interaction of immobilized human plasminogen and plasmin with streptokinase. AB - The complex of immobilized human plasminogen (iHPlg) and streptokinase (SK) has a lower catalytic activity in hydrolysis of plasmin-specific substrate S-2251 with a kcat/Km of 0.005 microM-1 x s-1, compared to 0.031 microM-1 x s-1 of immobilized human plasmin (iHPlm) and 0.078 microM-1 x s-1 of HPlm. The SK in the complex could be removed by acid buffer solution, and the iHPlg will remain catalytically active. IHPlm.SK complex could activate bovine plasminogen (BPlg), whereas iHPlg.SK complex could not. IHPlg could be activated by interaction with a combination of SK and HPlg or urokinase. The activated iHPlg.SK complex had the ability to activate BPlg as iHPlm.SK. The reasonable explanation is that iHPlg was converted to iHPlm in reaction with the combination of HPlg and SK. However, iHPlg was converted to a virgin enzyme in reaction with SK alone and could not activate BPlg. A new modified mechanism for the interaction of HPlg or HPlm with SK was proposed. PMID- 8363601 TI - A small influence of HSP90 levels on the trehalose and heat shock element inductions of the yeast heat shock response. AB - Heat shock protein (HSP) induction is only one change elicited in yeast by heat shock. Trehalose is also accumulated, while declining intracellular pH stimulates plasma membrane ATPase activity. Recently the trehalose induction was shown to be regulated by levels of HSP70 and, to a lesser extent, HSP104. Another HSP which might contribute to regulation is HSP90, especially as HSP90 forms complexes with heat shock transcription factor and several of the regulatory proteins of eukaryotic cells. This possibility was investigated using isogenic yeast strains with normal, decreased or elevated HSP90. The results show HSP90 levels having a small negative influence over the heat inductions of trehalose and the heat shock element, a minor effect compared with the major regulation exerted by HSP70. PMID- 8363602 TI - Inhibition of ret tyrosine kinase activity by herbimycin A. AB - We examined the effect of herbimycin A, a potent inhibitor of tyrosine kinases, on NIH(ret) cells and TPC-1 papillary thyroid carcinoma cells, both of which express the active ret genes. Herbimycin A reversed the morphology of NIH(ret) cells to flat cells with a concomitant reassembly of microfilament bundles. On the other hand, it did not induce a significant change in cell shape of TPC-1 cells. When tyrosine kinase activities of the active ret gene products in herbimycin A-treated NIH(ret) and TPC-1 cells were examined in immunocomplex kinase assays, they drastically decreased in both cells as compared with untreated cells. In addition, herbimycin A strongly inhibited tyrosine phosphorylation of 40 kDa and 31 kDa proteins present in the immunoprecipitates of both cells, suggesting that these proteins could associate with the Ret proteins. PMID- 8363603 TI - Characterization of HeLa nuclear factors which interact with a conditionally processed rat fibronectin pre-mRNA. AB - It is demonstrated that several HeLa nuclear proteins interact in a magnesium dependent fashion with a conditionally processed pre-mRNA derived from an alternatively spliced region of the rat fibronectin gene. HnRNP C proteins crosslink under both permissive and non-permissive conditions (high and low magnesium, respectively), whereas hnRNP I/PTB is observed only under the latter. Thus hnRNP I/PTB represents a potential inhibitor of splicing for this intron. A protein that was observed to crosslink under permissive conditions has been identified as splicing factor U2AF65, which thus represents a candidate positive factor in the splicing of this pre-mRNA. We interpret these results with a working model for the conditional selection of the 3' splice site of alternative exon EIIIB. PMID- 8363604 TI - Three-dimensional recognition requirements for angiotensin agonists: a novel solution for an old problem. AB - A novel approach involving the search for a common spatial arrangement of functionally important (pharmacophoric) groups in low-energy conformers of AT and its active analogs has been employed to determine the receptor-bound ("biologically active") conformation(s) for angiotensin II (Asp1-Arg2-Val3-Tyr4 Val/Ile5-His6-Pro7-Phe8, AT). The four pharmacophoric groups for AT are the aromatic moieties of Tyr4, His6 and Phe8 residues, as well as the C-terminal carboxyl. Geometrical comparison of the sets of low-energy backbone conformers for AT itself, and two analogs, [(alpha Me)Phe4]-AT and [Pro5]-AT, yielded the model for the receptor-bound conformation(s), which is compatible with cyclic AT analogs possessing substantial binding to specific AT receptors. A new analog, [D Tyr4, Pro5]-AT, was designed based on the proposed receptor-bound conformation. The analog showed a good affinity (IC50 = 42.8 nM) towards specific AT receptors. PMID- 8363605 TI - Lack of evidence for a role of Cys-138 as a base catalyst in the skeletal muscle 6-phosphofructo-2-kinase reaction. AB - The role of Cys-138 in the catalysis of the skeletal muscle 6-phosphofructo-2 kinase reaction was investigated by mutating this residue to serine, glutamine and alanine, expressing the mutants in E. coli with a T7 RNA polymerase-based expression system, and analyzing their kinetic properties. The Cys138Ala mutant had greatly diminished activity, while the Cys138Ser and Cys138Gln mutants had maximal velocities 2-3 fold higher than the wild-type enzyme. It was concluded that Cys-138 does not act as a base catalyst in the kinase reaction, but that it plays a significant structural role in the enzyme's active site. PMID- 8363606 TI - Novel affinity support prepared by crosslinking purified insulin receptors to agarose. AB - The insulin receptor interacts with other membrane proteins and possibly also a cytoplasmic second messenger(s) of insulin action. As an approach to identify and purify these ligands of the insulin receptor, we have developed an insulin receptor affinity support which retains the properties of the membrane associated insulin receptors. Insulin receptors first were purified from rat liver by affinity chromatography on wheat germ lectin agarose and insulin agarose. The purified insulin receptors then were crosslinked to agarose. The agarose immobilised insulin receptors had an affinity for insulin indistinguishable from the native receptors. In addition, insulin enhanced the autophosphorylation of the beta-subunit of these agarose immobilised insulin receptors. The insulin binding and autophosphorylation activities were stable for at least one week when this novel affinity support was stored at 4 degrees C. PMID- 8363607 TI - Cell density-dependent DNA fragmentation and its suppression by heparin in primary culture of adult rat hepatocytes. AB - We show here that the internucleosomal DNA fragmentation, which is a biochemical hallmark of apoptosis, was induced in a cell density-dependent manner in primary culture of adult rat hepatocytes. This DNA fragmentation could be suppressed by a gene expression inhibitor, indicating the active nature of this process. Moreover, the viability changes in high and low cell density cultures showed a tendency corresponding with the incidence of the DNA fragmentation in them. These results suggest that in hepatocytes there may be a cell density-dependent apoptosis mechanism. In this report, we also show that heparin could suppress this DNA fragmentation with high specificity, and the cell death to some extent. PMID- 8363608 TI - Organ distributions of liposome-loaded rat platelets. AB - Past in vitro functional assays have demonstrated that platelet function is not inhibited by liposome uptake. In the present study, the organ distributions of control and liposome-loaded Sprague-Dawley rat platelets were examined to determine whether liposome uptake enhances RES uptake. Platelets were isolated using STRactan density gradient centrifugation, incubated with small unilamellar liposomes in vitro for 1 hour, labeled with 51Cr and injected into a cohort group of rats. One hour post-injection the spleen, liver, lungs, blood, kidneys and bladder contents were removed and the percentages of the recovered dose localized per total organ (%RD) were determined. The RES index, defined as %RDliver + %RDspleen, were 24.8 +/- 4.5 and 20.5 +/- 5.0 for the control platelets and liposome-loaded platelets, respectively. These results indicate that liposome uptake does not enhance RES uptake. PMID- 8363609 TI - The uniquely distributed isoprenylated protein methyltransferase activity in the rat brain is highly expressed in the cerebellum. AB - Isoprenylated protein methyltransferase, the enzyme which catalyzes the reversible methylation of signal transducing G-proteins was studied in nine brain regions of the rat brain using S-farnesyl cysteine analogs as substrates. Enzyme activity, as determined with N-acetyl-S-farnesyl-L-cysteine (AFC) was found in the nuclear, synaptosomal and microsomal fractions of all brain regions but not in the cytosol. The enzyme is a unique methyltransferase with respect to its brain distribution. The rank order of activity of the enzyme is cerebellum >> midbrain > medulla > forebrain regions, where activities in cerebellar synaptosomal and nuclear fractions (28-32 pmol AFC [methyl-3H]ester formed/min/mg prot) are 20 to 30 times higher than those of the corresponding fraction of the forebrain regions. This distribution is reminiscent of that of neurotransmitter receptors and signal transduction molecules and suggests a regulatory role for the enzyme, particularly in the cerebellum. PMID- 8363610 TI - Inhibition of DNA repair and sensitization of cisplatin in human ovarian carcinoma cells by interleukin-1 alpha. AB - Interleukin-1 alpha induced an increase in both the cellular accumulation of cis diamminedichloroplatinum (II) (cisplatin) and DNA platination and significantly reduced the removal of platinum from DNA of human ovarian (NIH: OVCAR-3) carcinoma cells in culture. The combinations of IL-1 alpha and cisplatin were highly synergistic against these ovarian carcinoma cells and maximum levels of sensitization (15-20-fold) were observed during simultaneous exposure of cisplatin and IL-1 alpha. IL-1 alpha specific receptor antagonist decreased this synergy. These results strongly indicate that IL-1 alpha inhibits DNA repair, and this inhibition of DNA repair may explain, in part, a strong synergistic interaction between IL-1 alpha and cisplatin in NIH: OVCAR-3 cells. PMID- 8363611 TI - Butyric acid and its monosaccharide ester induce apoptosis in the HL-60 cell line. AB - Butyric acid is a potent cell growth inhibitor and differentiation inducer (1-4). However, the short plasma half-life of this fatty acid limits its potential therapeutic use (5,6). The recent synthesis of several monosaccharide esters of butyric sodium salt (BuONa) with a prolonged plasma half-life and similar biological properties as the sodium salt opens new perspectives (7-12). We report here that the human myeloid HL-60 cell line can be induced to apoptosis when cultured with one of these esters, monoacetone glucose 3-butyrate (MAG = 3but) or BuONa. Cytospin slide preparations and flow cytometric studies showed that HL-60 cells treated with 1 mM MAG = 3but or BuONa exhibited a reduction in cell volume and condensation of nuclear structure characteristic of apoptosis, associated with monocytic differentiation. Time course studies demonstrated that DNA fragmentation, as determined by agarose gel electrophoresis, was detected 4 hours after incubation with the drugs, while morphologic signs appeared at day 3. Apoptotic cells increased with culture time and reached a maximum at day 6 of 20 +/- 5% with BuONa, 25 +/- 5% with MAG = 3but, and only 5 +/- 2% in controls. These findings suggest that these drugs may exert their actions, at least in part, through induction of apoptosis. PMID- 8363612 TI - Isolation and structural characterization of the rat gene encoding the brain specific snRNP-associated polypeptide "N". AB - We isolated the gene encoding the brain specific snRNP-associated polypeptide "N" from a rat genomic library. Some intronless genes have previously been reported for this polypeptide in the rat. In contrast, our gene consists of at least nine exons (the last exon(s) encoding the 3'-end of the mRNA has not been isolated). The second intron of the gene is probably so long as to hamper the cloning of the complete gene into a single phage vector. Therefore, we used polymerase chain reaction amplification of the rat genome with oligonucleotides designed on the basis of known cDNA sequences that allowed us to isolate and clone the first two exons at the 5'-end of the gene. Primer extension studies revealed multiple transcription start sites, all of them contained within the first exon. The intron/exon organization coincides with the alternative splicing events suggested by the sequences of the various cDNA species isolated so far. As also reported by others, genomic Southern analysis suggests the presence of other genomic regions containing sequences strongly hybridizing to the cDNA. We isolated and characterized two of these regions. They contain sequences very similar to the cDNA, not interrupted by introns and flanked by a polyA tail at their 3'-ends; hence they are considered two different pseudogenes. PMID- 8363613 TI - Multi-level regulation of lysosomal gene expression in lymphocytes. AB - The expression of the gene coding for the lysosomal enzyme, beta-glucuronidase (Gus), was examined in functionally distinct T, B and plasma cell lines. Each of the different groups of cells had different intracellular levels of active Gus enzyme and numbers of Gus mRNA copies per cell. Analysis of the molecular forms of Gus mRNA and protein by Northern and Western blotting revealed that the different types of cells all produced a single mature 2.7 kb transcript and a 73 kDa polypeptide. However, the utilisation of the Gus mRNA to produce the Gus antigen, and the subsequent posttranslational processing of the polypeptide to generate the mature, enzymically active Gus, were found to be cell type-specific. Control of the functional expression of the Gus gene is thus exerted at both the transcriptional and translational levels, and appears to differ between different types of lymphocyte. PMID- 8363614 TI - Stoichiometry of the human lysosomal carboxypeptidase-beta-galactosidase complex. AB - The understanding of the lysosomal beta-galactosidase-carboxypeptidase neuraminidase multienzymatic complex structure and function requires an efficient system for dissociation and association of its isolated protein components under controlled conditions. In this paper such a system was used to determine the stoichiometry of the two main components of this complex--beta-galactosidase and carboxypeptidase. The complex, after affinity purification from human placenta, was dissociated at pH 7.5 and beta-galactosidase and carboxypeptidase were separated and purified to homogeneity by FPLC anion-exchange chromatography. The 680 kD complex of beta-galactosidase and carboxypeptidase was reconstituted in vitro by mixing the isolated enzymes in a 1:2 molar ratio at pH 7.5 and then progressively acidifying the medium towards the intralysosomal pH value of 4.75. Under the same conditions, beta-galactosidase and carboxypeptidase independently existed as 306 kDa tetramer and 98 kDa dimer, respectively. Reconstitution experiments with various ratios of purified beta-galactosidase and carboxypeptidase allowed us to conclude that the whole complex is made of 4 beta galactosidase and 8 carboxypeptidase monomers. Cross-linking of the native and reconstituted complexes with dimethylsuberimidate or glutaric dialdehyde suggested that the native and the reconstituted complexes have the same supramolecular structure. PMID- 8363616 TI - Conformational changes of human beta 1 thyroid hormone receptor induced by binding of 3,3',5-triiodo-L-thyronine. AB - To understand the structural basis in the hormone-dependent transcriptional regulation of human beta 1 thyroid hormone receptor (h-TR beta 1), we studied the conformational changes of h-TR beta 1 induced by binding of 3,3',5-triiodo-L thyronine (T3). h-TR beta 1 was treated with trypsin alone or in the presence of T3, thyroid hormone response element (TRE) or T3 together with TREs. Without T3, h-TR beta 1 was completely digested by trypsin. Binding of TREs had no effect on the tryptic digestion pattern. However, T3-bound h-TR beta 1 became resistant to tryptic digestion and yielded trypsin-resistant peptide fragments with molecular weight of 28,000 and 24,000. Chymotryptic digestion also yielded a T3-protected 24 Kd peptide fragment. Using anti-h-TR beta 1 antibodies and amino acid sequencing, the 28 Kd fragment was identified to be Ser202-Asp456. The 24 Kd tryptic fragments were found to be Lys239-Asp456 and Phe240-Asp456. The 24 Kd chymotryptic fragment was identified to be Lys235-Asp456. The structural changes as a result of T3 binding could serve as a transducing signal to modulate the gene regulating activity of h-TR beta 1. PMID- 8363615 TI - GTP-binding protein couples with metabotropic glutamate receptor in bovine retinal on-bipolar cell. AB - GTP-binding protein (G protein) linking to metabotropic glutamate receptor of bovine retinal on-bipolar cell was studied by use of pharmacologically selective ligands, 2-amino-4-phosphonobutyric acid (APB) on bacterial toxin-catalyzed ADP ribosylation and GTP gamma S-binding. In contrast to the electrophysiological findings reported, G protein coupling to APB-sensitive glutamate receptor served as a substrate for pertussis toxin but did not for cholera toxin. Several glutamate analogues effective on on-bipolar cell, as well as APB, increased GTP gamma S binding to retinal membranes devoid of rod outer segments. The enhancement of GTP gamma S binding by APB was completely abolished when the membranes were pretreated with pertussis toxin and NAD. These results suggest that, in retinal on-bipolar cell, the G protein which couples metabotropic glutamate receptor to hyperpolarizing response of the cell is sensitive to pertussis toxin. PMID- 8363618 TI - Control of heme polymerase by chloroquine and other quinoline derivatives. AB - To evaluate the response of heme polymerase to treatment of malaria with chloroquine, we used mice infected with Plasmodium berghei. Six hours after treatment with 3 mumoles of chloroquine intraperitoneally per mouse, heme polymerase activity in parasitized erythrocytes decreased from 238 to 37 nanomoles of ferriprotoporphyrin IX polymerized per hour per mumole of ferriprotoporphyrin IX in preformed hemozoin, and nonhemozoin ferriprotoporphyrin IX increased in vivo from 40 to 123 nanomoles per ml of packed, parasitized erythrocytes. Other 4-aminoquinoline derivatives were similar in effect to chloroquine. Treatment with quinine, mefloquine, primaquine, or naphthalene derivatives caused no reduction in heme polymerase activity. In contrast to 4 aminoquinoline derivatives, quinine and mefloquine, which are quinolinemethanol derivatives, antagonized the effect of chloroquine. PMID- 8363617 TI - UTP activates phospholipase C-Ca2+ system through a receptor different from the 53-kDa ATP receptor in PC12 cells. AB - Extracellular ATP (a purine nucleotide) and UTP (a pyrimidine nucleotide) both activated phospholipase C with a similar potency and efficacy; however, in contrast to ATP which induced a remarkable norepinephrine release, UTP-induced norepinephrine release was small in PC12 cells, a rat pheochromocytoma cell line. ATP, its derivatives (2-methylthioadenosine 5'-triphosphate (MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP)) and UTP increased intracellular Ca2+ in the presence of 2 mM extracellular Ca2+ with the potency order of ATP > MeSATP > BzATP = UTP. Under the low extracellular Ca2+ conditions, the Ca2+ response to purine nucleotides was markedly reduced, but the UTP response was not. The [32P]BzATP labeling of a 53-kDa putative ATP receptor coupled to a channel system (Majid, M.A., Okajima, F., and Kondo, Y. (1992) Biochim. Biophys. Acta 1136, 283-289) was markedly inhibited by ATP, but not by UTP. These results suggest that UTP activates the phospholipase C-Ca2+ system through a receptor different from the 53-kDa ATP receptor. PMID- 8363619 TI - Neuron-specific splicing of the Alzheimer amyloid precursor protein gene in a mini-gene system. AB - Several forms of Alzheimer amyloid precursor protein (APP) mRNA are generated by alternative splicing. Among them, the APP695 mRNA skipping the exon 7 and 8 is expressed specifically in neurons, suggesting that this alternative splicing is regulated in a neuron-specific manner. As the first step for investigating the mechanism of the neuron-specific splicing, a mini-gene system was developed, in which mini-APP genes consisting of the exon 6, 7, 8, 9 and their flanking regions were introduced into neuronal and nonneuronal cultured cell lines to see their expression profiles. In the system the exon 7 and 8 of the mini-gene were significantly skipped in the neuronal cell, and the deletion study indicated that cis-acting elements for skipping the exons existed in the corresponding skipped exon and its flanking regions. A small deletion upstream of the exon 8 suppressed the skipping of the exon 8 in the neuronal cell, suggesting that one of the regulatory sequence(s) for the exon skipping exists in a small region upstream of the skipped exon. PMID- 8363620 TI - Computational studies on the decarboxylation of 2-(1-carboxy-1-hydroxyethyl)-3,4 dimethylthiazolium dipolar ion, an analog of the complex of pyruvic acid and coenzyme of the pyruvate decarboxylase. AB - We have obtained the optimized geometrical structure of 2-(1-carboxy-1 hydroxyethyl)-3,4-dimethylthiazolium dipolar ion and investigated its geometric and electric changes during decarboxylation process by the MNDO-PM3 method, a molecular orbital method. The salient features of the optimized structure are that the dihedral angle of C4-C1-C2-S3 is 5.4 degrees and the distance between thiazolium S3 and carboxyl O6 is about 1.8 A (the bond order between S3 and O6 is about 0.4). The lowest energy decarboxylation profile is the following process. First the dihedral angle of C4-C1-C2-S3 becomes about 90 degrees, then the distance between C1-C2 increases while the dihedral angle holds about 90 degrees, and finally the C1-C2 bond disappears. The most remarkable change caused by the 90 degrees rotation is the disappearance of the S3-O6 bond, and this disappearance causes electric changes that prompt the decarboxylation. PMID- 8363621 TI - Transport of the immunosuppressant 15-deoxyspergualin in human peripheral blood lymphocytes. AB - 15-deoxyspergualin (DSG) is a potent immunosuppressive compound currently in clinical trials. In this study, we have characterized the uptake and intracellular localization of DSG in human peripheral blood lymphocytes (PBL's). DSG is transported into human PBL's and reaches an estimated maximum concentration of approximately 500 microM in 6 hours. The majority of the [3H] DSG remains in the cytoplasm of cells and that which is associated with the nucleus is only loosely associated. DSG was transported by HeLa cells, as well, suggesting uptake is not specific for hematopoietic cells. Positively charged amino acids and polyamines, which are structurally similar to DSG, were unable to compete for DSG transport suggesting that DSG is transported into cells via a pathway distinct from amino acids or polyamines. PMID- 8363622 TI - Effects of changes in gonadal hormones on the amount of aromatase messenger RNA in mouse brain diencephalon. AB - Aromatase in brain is known to play a crucial role in development and maintenance of androgen dependent sexual behavior of males. Biochemical studies have shown that the aromatase activity in brain is influenced by androgen. In this study, we measured the aromatase mRNA content of mouse brain quantitatively to gain a deeper insight into this phenomenon. We found that in the diencephalic area it is sexually dimorphic, as reported for aromatase activity. The amount of aromatase mRNA in this area in males was 150% higher than that in females and decreased to the level in females after castration. The content of aromatase mRNA in castrated males was elevated by 2-fold by injection of testosterone and restored to the level observed in intact males. Injection of testosterone also affected the level of aromatase mRNA in normal mice of both sexes, though to lesser extent. On the contrary, injection of estrogen decreased the amount of aromatase mRNA in gonadectomized mice of both sexes. These results show that transcriptional control of the aromatase gene is involved in the mechanism of testosterone to affect sexual behavior. PMID- 8363623 TI - Effects of added albumin on the kinetic isotope effect observed in the microsomal oxidative demethylation of the methoxyl group. AB - The kinetic deuterium isotope effect on the microsomal oxidative demethylation of methoxyl groups was measured using methoxychlor, an insecticide, as a model compound. When the metabolic reactions were conducted in the presence of bovine serum albumin, the observed isotope effect was smaller than that in its absence. The values were unaltered when the albumin concentration was changed from 1% to 2%. The results were interpreted by the alteration of the ES-complex formation/dissociation rate with the interaction between substrate and albumin. PMID- 8363624 TI - Bio-metabolism of green S and indigo carmine through caecal microflora of rats. AB - Bio-metabolism of two permitted food colours viz., Green S and Indigo Carmine, through caecal microflora of rats was investigated. Incubation of Green S with caecal flora resulted in one coloured and two fluorescent metabolites with the corresponding Rf values of 0.83, 0.33, 0.22, respectively. Indigo carmine was metabolized by caecal microflora to four [corrected] fluorescent metabolites with Rf values of 0.09, 0.27, 0.5 and 0.72. The DI 50 value of Green S was considerably higher (456 min) as compared to that of Indigo carmine (54 min). These results suggest that Green S and Indigo carmine are biotransformed to a variety of metabolites by rat caecal microflora. PMID- 8363626 TI - Strong promoter activity of human and rat islet amyloid polypeptide/amylin gene constructs in mouse beta cells (betaTC3). PMID- 8363625 TI - Attachments of pentaammineruthenium(III) to Trichoderma reesei cellobiohydrolase I increases its catalytic activity. AB - Pentaammineurthenium(III) was covalently attached to cellobiohydrolase I (CBH I, EC 3.2.1.91), the major component of Trichoderma reesei cellulase, resulting in 0.7 mol ruthenium/mol CBH I and an electrode potential of +95 mV. Fractionation of modified CBH I by chromatofocusing resulted in the separation of fractions with a 1.4- to 3.2-fold increase in specific activity toward p nitrophenylcellobioside, depending on the assay conditions, over that of native enzyme. The extent of the hydrolysis of insoluble cellulosic substrates (Avicel and newsprint) to glucose by modified CBH I was also greater than that observed by the native enzyme. PMID- 8363627 TI - Protein identification by mass profile fingerprinting. AB - We have developed an algorithm for identifying proteins at the sub-microgram level without sequence determination by chemical degradation. The protein, usually isolated by one- or two-dimensional gel electrophoresis, is digested by enzymatic or chemical means and the masses of the resulting peptides are determined by mass spectrometry. The resulting mass profile, i.e., the list of the molecular masses of peptides produced by the digestion, serves as a fingerprint which uniquely defines a particular protein. This fingerprint may be used to search the database of known sequences to find proteins with a similar profile. If the protein is not yet sequenced the profile can serve as a unique marker. This provides a rapid and sensitive link between genomic sequences and 2D gel electrophoresis mapping of cellular proteins. PMID- 8363628 TI - Simultaneous resistance to vincristine and adriamycin appears at higher frequencies than to vincristine and etoposide in Chinese hamster ovary cells. AB - Efficacy of combination chemotherapy depends on the probability of a cell being resistant to at least two drugs simultaneously. In this study, we determined the frequencies of double drug resistance in the CHO AA8 cell line under combined exposure to vincristine plus adriamycin, vincristine plus etoposide, and adriamycin plus etoposide. These frequencies were compared to the expected frequencies which are the product of the independent frequencies observed for each drug alone. The results show a high frequency (up to 700-fold) of double resistance to adriamycin plus vincristine, a low increase (up to 30-fold) in frequency of resistance to vincristine plus etoposide, and an intermediate increase (200 to 300-fold) in frequency of cells resistant to adriamycin plus etoposide. The differences observed between combinations seem to be related, at least in part, to the mechanism(s) of resistance generally involved in the resistance to each drug: P-glycoprotein overexpression and/or DNA topoisomerase II alteration. PMID- 8363629 TI - Validation and use of cloned, expressed human drug-metabolizing enzymes in heterologous cells for analysis of drug metabolism and drug-drug interactions. PMID- 8363630 TI - Inhibition by Ro 31-8220 of acid secretory activity induced by carbachol indicates a stimulatory role for protein kinase C in the action of muscarinic agonists on isolated rat parietal cells. AB - The bisindolylmaleimide Ro 31-8220 is a selective inhibitor of protein kinase C. This compound was used to investigate the involvement of protein kinase C in the stimulation of gastric acid secretion by the muscarinic cholinergic receptor on rat isolated parietal cells. The accumulation of the weak base aminopyrine by both crude and enriched preparations of parietal cells was used as an index of secretory activity. Ro 31-8220 antagonized (IC50, 1.0 microM) the effect of the activator of protein kinase C,12-O-tetradecanoylphorbol 13-acetate (TPA), on histamine-stimulated aminopyrine accumulation. Ro 31-8220 (0.1-2.14 microM) inhibited the aminopyrine response to 0.1 mM carbachol (IC50, 0.78 microM; 49% inhibition at 2.14 microM Ro 31-8220) and shifted the dose-response curve for the effect of carbachol concentration of aminopyrine accumulation downwards and to the right. No inhibition of aminopyrine accumulation induced by histamine was found with Ro 31-8220 (0.1-2.14 microM). In a preparation containing > 80% parietal cells incubated with 0.1 mM carbachol, 2.14 microM Ro 31-8220 inhibited aminopyrine accumulation by 43%, but had no effect on the increase in intracellular Ca2+ which was measured by using the fluorescent probe FURA-2. In conclusion, Ro 31-8220 (0.1-2.14 microM) produced a selective reduction in secretory activity in parietal cells by inhibition of protein kinase C. The predominant role of protein kinase C in parietal cells activated with carbachol is not to cause feedback inhibition of the response but to facilitate stimulation of secretory activity. PMID- 8363631 TI - Taurine protects against the cytotoxicity of hydrazine, 1,4-naphthoquinone and carbon tetrachloride in isolated rat hepatocytes. AB - Exposure of rat hepatocytes to hydrazine, carbon tetrachloride or 1,4 naphthoquinone results in cytotoxicity determined as uptake of Trypan blue and leakage of lactate dehydrogenase (LDH). After exposure of hepatocytes to hydrazine and 1,4-naphthoquinone, ATP was also measured and was found to be depleted. Addition of the beta-amino acid taurine to the hepatocyte incubation buffer partially protects the cells against the cytotoxicity of these three different cytotoxic compounds, as indicated by Trypan blue uptake and LDH leakage. Taurine also reduces the depletion of ATP caused by 1,4-naphthoquinone but not hydrazine. It is suggested that taurine may have a cytoprotective effect in vitro and may be a useful tool for the investigation of mechanisms of cytotoxicity. PMID- 8363632 TI - Suicide inhibition of monoamine oxidases A and B by (-)-deprenyl. A computer aided solution for determining inhibition specificity. AB - An analytical solution to the differential equations describing the kinetics of the suicide inhibition of a two-enzyme system has been derived and the modelling of suicide inhibition of the monoamine oxidases A and B (MAO A and B, EC 1.4.3.4) by a quasi-selective agent, (-)-deprenyl, is presented as an example. A new parameter, the specificity index is defined and used in a model which describes the specific and non-specific binding of (-)-deprenyl to MAO B and MAO A, respectively. This type of analysis may be of therapeutic value by indicating optimal dosage of quasi-selective MAO B inhibitors for the treatment of Parkinson's disease. PMID- 8363633 TI - Metabolism of methylamine by semicarbazide-sensitive amine oxidase in white and brown adipose tissue of the rat. AB - The metabolism of [14C]methylamine (MA) by amine oxidase activity in rat white and brown adipose tissue homogenates, and in mature adipocytes from these tissues has been studied. Oxidation of MA was completely inhibited by 0.1-1 mM semicarbazide, without being affected by the monoamine oxidase (MAO) inhibitor, pargyline (1 mM), indicating that MA is metabolized by semicarbazide-sensitive amine oxidase (SSAO) and not by MAO. The mean Km for MA deamination in all of these sources was around 250-300 microM. SSAO activity towards MA was also demonstrated in white and brown pre-adipocytes, transformed to the adipose phenotype by treatment in culture for 7 days with lipogenic agents. These results are similar to previous findings that SSAO in vascular smooth muscle is able to metabolize aliphatic amines such as MA, and furthermore suggest that SSAO may play a role in adipose tissue function and/or maturation. PMID- 8363634 TI - Changes in monoamine oxidase activity in mouse brain associated with d methamphetamine dependence and withdrawal. AB - The long-term effects of d-methamphetamine (MP, 5 mg/kg) on brain mitochondrial monoamine oxidase (MAO) activity were studied in mice given MP intraperitoneally daily for 4 weeks. The MAO activities decreased when serotonin (5-HT) and dopamine (DA) were used as substrates. A marked elevation in MAO activity was seen during MP withdrawal when 5-HT, DA, beta-phenylethylamine (beta-PEA) and norepinephrine (NE) were used as substrates. The kinetics of MAO showed a significant decrease in Km values, but no significant change in Vmax values during MP withdrawal, despite the presence of NE. The Km and Vmax values increased when NE was the substrate. Inhibition of MAO by MP or its metabolites (amphetamine, p-hydroxyamphetamine and p-hydroxymethamphetamine) increased with the use of the following substrates in the order: DA, 5-HT, NE and beta-PEA. PMID- 8363635 TI - Are lethal effects of nitracrine on L5178Y cell sublines associated with DNA protein crosslinks? AB - Nitracrine (Ledakrin, 1-nitro-9-(3,3-N,N-dimethylaminopropylamino)-acridine) is of interest as a DNA intercalator and alkylator with very high cytotoxic potency, especially against hypoxic cells. DNA-DNA crosslinks [Konopa et al., Chem Biol Interact 43: 175-197, 1983; Pawlak et al., Cancer Res 44: 4289-4296, 1984] or DNA protein crosslinks (DPCs) [Woynarowski et al., Biochem Pharmacol 38: 4095-4101, 1989; Szmigiero and Studzian, Biochim Biophys Acta 1008: 339-345, 1989] are related to the toxicity of the drug. The cytotoxic effect of and DNA damage induced by nitracrine were measured in two sublines of mouse lymphoma L5178Y, LY R (resistant to ionizing radiation) and LY-S (sensitive to ionizing radiation). LY-R cells were more sensitive to nitracrine (D10 = 0.11 microM) than LY-S (D10 = 0.35 microM) when treated for 1 hr at 37 degrees. To a DNA-DNA crosslinking agent, mitomycin C, the comparative sensitivity was opposite. LY-R cells were more resistant to this drug than LY-S cells (D10 = 7.1 vs 2.3 microM). DNA damage induced by nitracrine was measured by the alkaline elution method and by nitrocellulose filter binding assay. Nitracrine treatment with biologically relevant concentrations (0.1-3.0 microM, 1 hr, 37 degrees) induced only DPCs. Interstrand crosslinks and DNA breaks were not detected. Nitracrine produced about two times more DPCs in LY-R cells than in LY-S cells. Both sublines removed 50% of initial lesions during 2 hr post-treatment incubation. The greater sensitivity of LY-R cells to nitracrine is thus not related to the efficiency of DNA repair, but may be a consequence of enhanced initial damage in the form of DPCs. This finding is consistent with the latter lesion being responsible for the cytotoxicity of nitracrine. PMID- 8363636 TI - Changes in amounts of cytochrome P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes. AB - Hepatic microsomal cytochrome P450s, which are involved in the metabolism of drugs, hormones, prostaglandins and fatty acids, change when animals develop diabetes. We studied changes in cytochrome P450 isozymes in both hepatic and renal microsomes of rats with diabetes caused by streptozocin, and compared the results with changes in catalytic activities in the microsomes. In hepatic microsomes of diabetic rats, the amount of cytochrome P450 2E1, an acetone inducible isozyme, was two and a half times that of control rats, and that of P450 4A2, a major renal isozyme, was three times that in the controls. The amounts of cytochrome P450s 2A1, 2C6, 2C7, 3A2 and 4A3 increased in hepatic microsomes of diabetic rats, and P450 2C11 decreased. Treatment with insulin restored these to the levels in the controls. The catalytic activities of aniline hydroxylation, 7-ethoxycoumarin O-dealkylation, testosterone 2 beta, 6 beta, 7 alpha, and 16 beta-hydroxylation, and omega-, (omega-1)-hydroxylation of lauric acid were high in the hepatic microsomes of diabetic rats, and testosterone 2 alpha and 16 alpha-hydroxylation activities were low. In renal microsomes of diabetic rats, cytochrome P450s 2E1, 4A2 and K-4 were induced, and omega- and (omega-1)-hydroxylation activities were high. These changes were reversed by insulin treatment. The induction and suppression of cytochrome P450 isozymes in diabetic rats were consistent with the changes in the catalytic activities. In both hepatic and renal microsomes, P450s 2E1 and 4A2 were induced, altered metabolism of ketones and fatty acids in diabetes may contribute to these changes. PMID- 8363637 TI - Reduction in the numbers of muscarinic receptors by an endogenous protein. AB - The soluble fraction from the ileal longitudinal muscle of guinea pigs was examined for the presence of an endogenous modulator of muscarinic receptors. In the presence of the soluble fraction, the binding of [3H]quinuclidinyl benzilate to the membranes from the tissue was inhibited in a concentration-dependent manner. The inhibitory activity in the soluble fraction was heat stable, but was inactivated by trypsin treatment. Several protease inhibitors had no effect on the inhibitory activity. These results suggest the existence of an endogenous protein that inhibits the binding of the muscarinic ligand to the receptor. Ultrafiltration demonstrated that the protein factor had a molecular mass of more than 10,000 Da. Saturation binding and dissociation kinetic experiments indicate neither a competitive nor allosteric mode of inhibitory action and suggest that an irreversible block or internalization of muscarinic receptors is induced by the endogenous protein. PMID- 8363638 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced ethoxyresorufin-O-deethylase (EROD) and aldehyde dehydrogenase (ALDH3) activities in the brain and liver. A comparison between the most TCDD-susceptible and the most TCDD-resistant rat strain. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent inducer of ethoxyresorufin O-deethylase (EROD) and aldehyde dehydrogenase (EC 1.2.1.3., ALDH3) enzyme activities in the liver. Little is known about their inducibility by TCDD in the brain, although it may be a target organ for TCDD toxicity. Two strains of rat, Long-Evans (L-E) and Han/Wistar (H/W) exhibit an over 1000-fold difference in their LD50-values for TCDD. The induction of EROD and ALDH3 in discrete brain regions and in the liver of L-E and H/W rats were now compared at 10 days after TCDD exposure to assess the role of these responses in the strain difference. Liver EROD and ALDH3 were maximally induced at 5 micrograms/kg and 50 micrograms/kg, respectively, in both strains. In the brain 50 micrograms/kg TCDD was mostly needed to enhance EROD activity in both strains. The induction occurred especially in olfactory bulbs, but was also seen in the midbrain plus thalamus of both rat strains. The induced EROD activity in the olfactory bulb was almost totally abolished by a monoclonal antibody (Mab) 1-7-1 raised against CYP1A1. ALDH3 activities were increased more dose dependently in olfactory bulbs of H/W than L-E rats. In other brain areas measured, ALDH3 activities were induced more in L-E rats. Kinetic factors did not explain the differential induction of EROD and ALDH3 among discrete brain regions. We conclude that both EROD and ALDH3 are induced in the brain by TCDD although the activities are much lower than in the liver. The induction in the brain is region specific with olfactory bulbs being the most responsive area. As in the liver, the TCDD-induced activity of EROD in the brain is primarily associated with CYP1A1. According to the present findings, enzyme induction in the brain does not seem to have a crucial role in determining the strain susceptibility to the acute lethality of TCDD. PMID- 8363639 TI - Characterization of the transport system of prostaglandin A2 in L-1210 murine leukemia cells. AB - Prostaglandin (PG) A2 has been shown to be actively incorporated into mammalian cells and transferred to the cell nucleus. To characterize the properties of the PGA2 transfer system, we examined the status of PGA2 in L-1210 cells with modified cellular glutathione (GSH) levels. PGA2 in the cytosol fraction of the cells existed in its free-form, the GSH conjugate-form and a macromolecule associate-form (protein bound-form). When the GSH level was lowered under culture conditions, the amount of free-form increased while that of the protein bound form was unchanged. When PGA2-loaded cells were incubated in a salt solution, free- and conjugate-forms were emitted from the cells. A concomitant decrease and increase of protein bound PGA2 in cytosol and nuclei, respectively, were observed. Subsequent studies with isolated cellular fractions revealed that PGA2 bound to cytosolic protein was transported into the nuclear interior in a temperature-dependent manner. The binding of PGA2 to the protein and subsequent transport to the nuclei were inhibited by PGJ2 and 4-hydroxy-cyclopentenone, but not by PGB2, PGD2, PGE2, PGF2 alpha, arachidonic acid or oleic acid. N Ethylmaleimide (NEM) and p-chloromercuribenzoate (PCMB) strongly interfered with these transfer processes, suggesting that sulfhydryl components are involved in the transport of PGA2. Subfractionation of cytosol by gel chromatography proved the presence of two proteins (100-150 kDa and 25-35 kDa) that are capable of transporting PGA2 to cell nuclei. Though 40-45 kDa proteins, which correspond to GSH S-transferases, bound to PGA2, they lacked the nuclear transport activities. PMID- 8363640 TI - Association of galactosamine-induced hepatitis in the rat with hyperhyaluronanaemia and decreased hyaluronan uptake by the isolated, perfused liver. AB - Plasma hyaluronan (HA) concentration and the rate of HA uptake by the isolated, perfused liver were measured in rats treated with saline, D-galactosamine (GaI NH2, 50 mg/100 g body wt), gadolinium chloride (GdCl3) (0.5 mg/100 g body wt), and GdCl3 + GaI-NH2. GdCl3 was given 24 hr before GaI-NH2 or saline. Plasma L alanine:2-oxoglutarate aminotransferase (EC 2.6.1.2), a marker for hepatocyte damage, was increased by 8 hr and remained elevated for 24 hr after GaI-NH2 injection. GdCl3 did not affect plasma enzyme levels when given alone or in association with, but prior to, GaI-NH2. Plasma HA levels were increased (200%) within 24 hr after GaI-NH2 administration. A plateau was reached at 8 hr, which was maintained for at least 24 hr. Although GdCl3 alone did not affect plasma HA levels, it slightly delayed the increase in HA concentration in GaI-NH2-treated rats. Livers, isolated 24 hr after GaI-NH2 treatment, exhibited a severe depression (approximately 67%) of HA uptake. GdCl3 did not prevent this suppression. The data presented indicate that: (1) one of the sinusoidal endothelial cell-dependent functions of the liver, i.e. removal of HA from the blood stream, is profoundly impaired during galactosamine-induced hepatitis, and (2) the adverse effect of GaI-NH2 on this sinusoidal endothelial cell function may not be dependent on CdCl3-suppressible Kupffer cell functions. PMID- 8363641 TI - Effects of calcium channel antagonists on the phosphorylation of major protein kinase C substrates in the rat hippocampus. AB - K(+)-induced depolarization of rat hippocampal slices resulted in significant increases in the phosphorylation state of myristoylated, alanine-rich C kinase substrate (MARCKS; also known as 87K, pp80) and neuromodulin [also known as growth associated protein 43 (GAP43), B50, F1] as determined by back phosphorylation using protein kinase C. The effect of organic and inorganic Ca2+ antagonists on the phosphorylation of these major protein kinase C substrates in the rat hippocampus was studied to determine whether Ca2+ influx through L- or N type voltage-sensitive Ca2+ channels was required for the phosphorylation changes observed. The depolarization-induced changes appeared to be dependent on extracellular Ca2+, based on evidence indicating that the chelation of extracellular Ca2+ with ethylene glycol-bis (beta-amino-ethyl ether)-N,N,N',N' tetraacetic acid (EGTA) inhibited these changes. In addition, pretreatment of the slices with 500 microM Cd2+, but not 300 nM nimodipine, 10 microM omega-conotoxin GVIA or 10 microM MK-801, blocked the K(+)-induced change in phosphorylation. These results suggest that K(+)-induced changes in the phosphorylation of MARCKS and neuromodulin are mediated by Ca(2+)-dependent mechanisms other than, or in addition to, those sensitive to the organic Ca2+ channel antagonists employed. PMID- 8363642 TI - Induction of rat liver drug-metabolizing enzymes by heterocycle-containing mono-, di-, tri- and tetra-arylmethanes. AB - The effect of a nitrogen heterocycle constituent on the ability of arylmethanes to induce phase I and phase II drug-metabolizing enzymes has been examined. Rats were treated with tetra-, tri-, di- or monoarylmethane compounds daily for 3 days at a dose of 75 mg/kg. Induction of UDP-glucuronosyltransferase (morphine) activity was seen with twelve of the eighteen compounds investigated, and for three compounds it occurred independent of any induction of cytochrome P450. Induction of glutathione S-transferase activity was seen with ten of the compounds and was generally paralleled by changes in overall cytochrome P450 concentration and in both pentoxyresorufin and erythromycin dealkylase activities. Major induction of ethoxyresorufin deethylase activity was only apparent with two diarylmethanes that contained a 1-substituted imidazole moiety. UDP-glucuronosyltransferase (1-naphthol) activity was coinduced by these two compounds. A third compound, diphenyl-4-pyridylmethane, induced UDP glucuronosyltransferase (1-naphthol) activity without increasing ethoxyresorufin deethylase activity. Cytosolic sulfotransferase activity was not induced by the administration of any compound in this study. Among arylmethane derivatives, the presence of two aryl groups appeared to be a minimum requirement for induction of drug-metabolizing enzymes. If one of the aryl groups was not a heterocycle, or if the nitrogen atom of the heterocycle was sterically hindered, major induction of cytochrome P450 did not occur. With triarylmethanes, induction was independent of whether the heterocycle was imidazole, pyridine or pyrimidine. PMID- 8363643 TI - Interaction of adriamycin aglycones with isolated mitochondria. Effect of selenium deficiency. AB - Adriamycin (AdM) aglycones have dramatic effects on isolated heart mitochondria, oxidizing pyridine nucleotides, modifying sulfhydryl groups, and triggering a permeability transition of the inner membrane that results in free passage of solutes smaller than 1500 Da. In this investigation, the role of glutathione (GSH) peroxidase in these actions of the aglycones was evaluated, by comparing mitochondria from selenium-deficient and selenium-supplemented rats, with the following results. Selenium deficiency was without effect on the permeability transition of heart mitochondria, followed via Ca2+ release and triggered by AdM aglycone or by t-butyl hydroperoxide (TBH) or H2O2, both of which are authentic substrates of the peroxidase. The permeability transition of liver mitochondria was delayed by selenium deficiency regardless of the triggering agent; however, substantial triggering by the aglycone and TBH persisted in mitochondria from selenium-deficient animals. Selenium deficiency inhibited thiol modification elicited by AdM aglycone and H2O2 in heart mitochondria and by the aglycone, TBH, and possibly H2O2 in liver mitochondria. It would thus appear that AdM aglycone, TBH, and H2O2 can induce the permeability transition of isolated heart mitochondria via a process (or processes) distinct from the catalytic activity of the peroxidase. Furthermore, even in liver, where involvement of the peroxidase is observed, mechanisms other than the GSH cycle can contribute to transition induction by the aglycone and by TBH. Finally, mitochondrial-SH group modification by the aglycones appeared not to be causally linked to induction of the permeability transition. This laboratory has suggested that the effects of aglycone metabolites of AdM on mitochondria mediate the cardiotoxicity that limits use of the parent drug. The data presented in this paper argue against the involvement of GSH peroxidase in that process. They are in agreement with in vivo studies, which have generally failed to find evidence for amelioration of AdM cardiotoxicity in selenium-deficient animals. PMID- 8363644 TI - 9-cis-retinoic acid: a direct-acting dysmorphogen. AB - Experiments in vitro with cultured rat conceptuses demonstrated that 9-cis retinoic acid (9-cis-RA) (300 ng/mL amniotic fluid) produced branchial arch and somite defects similar to those elicited by equal concentrations of all-trans retinoic acid (all-trans-RA), but with an increase in cephalic defects that included missing optic vesicles. After conceptuses were intraamniotically microinjected with 600 ng 9-cis-RA/mL amniotic fluid on day 10 of gestation, an unusual heart defect was also observed. HPLC analyses indicated that 9-cis-RA readily underwent conversion to the less active metabolite, 13-cis-retinoic acid (13-cis-RA), in cultured conceptuses during the first 4 hr after treatment but only after 6 hr could elevated levels of the potent dysmorphogen all-trans-RA be detected. In separate experiments, conversion of 13-cis-RA or of all-trans-RA to 9-cis-RA could not be detected during a 6-hr embryo culture period. Endogenous levels of 9-cis-RA in whole rat embryos also were below limits of detection but small quantities of this isomer could be detected in neonatal rat eye and human embryonic brain. Our present study strongly suggests that 9-cis-RA is a direct acting dysmorphogen with probable specific target sites of action. PMID- 8363645 TI - Membrane permeation mechanisms of 2',3'-dideoxynucleosides. AB - The mechanism of membrane permeation of several 2',3'-dideoxynucleosides was investigated at 37 degrees with human erythrocytes using an "inhibitor-stop" assay. Transport (per 5 microL cells) via the nucleoside and nucleobase carriers was assessed by inhibition of influx with dilazep and adenine, respectively. Mechanisms of cellular entry were highly individualized: 2',3'-dideoxyadenosine and 3'-deoxythymidin-2'-ene via nonfacilitated diffusion, with high rates; 2',3' dideoxyguanosine mainly via the nucleobase carrier (Km = 390 microM, Vmax = 32 pmol/sec); 2',3'-dideoxyinosine by both nucleobase (Km = 850 microM, Vmax = 2.7 pmol/sec) and nucleoside (Km = 7.4 mM, Vmax = 16 pmol/sec) carriers, with a low rate of nonfacilitated diffusion; and 2',3'-dideoxycytidine, equally by the nucleoside carrier (Km = 23 mM, Vmax = 65 pmol/sec) and by nonfacilitated diffusion, with a low rate. These results demonstrate that the nucleobase carrier plays an important role in the influx of two of these dideoxynucleotides and that nonfacilitated diffusion is not necessarily the chief mode of membrane permeation of this class of drugs. PMID- 8363646 TI - Prevention of neocarzinostatin-induced cell death and morphologic change in SK-N SH human neuroblastoma cells by continuous exposure to nerve growth factor. AB - Neocarzinostatin is an antineoplastic agent that induces differentiated morphology in human (SK-N-SH) neuroblastoma cells in culture. We have compared this morphological differentiation with that induced by the endogenous differentiation inducer, nerve growth factor (NGF), and have explored the effects of exposure to NGF upon the morphological changes induced by neocarzinostatin in SK-N-SH cells. Both NGF and neocarzinostatin induced process outgrowth in these cells. The processes formed in the presence of NGF however, were shorter and thinner than those induced by neocarzinostatin. Furthermore, only neocarzinostatin induced enlargement of the somata of the cells, and caused cell death in a concentration-dependent fraction of the culture. These distinguishing features of treated cells allowed us to determine whether or not NGF exposure altered responsiveness of the cells to neocarzinostatin. NGF (100-1000 ng/mL) protected SK-N-SH cells from the morphological and cytocidal effects of neocarzinostatin (1-hr exposure, 0.017 to 0.033 micrograms/mL). Protection from neocarzinostatin required that NGF be continuously present for a period beginning 24 hr prior to neocarzinostatin exposure and continuing for the duration of the experiment, implying that the protection afforded by NGF has a latency necessitating pretreatment, and is reversible. These results suggest that neocarzinostatin is taken up by the cells and can exert its effects once NGF is removed, even after neocarzinostatin is washed out of the medium. The signal transduction cascade triggered by NGF receptor binding may prevent the action of neocarzinostatin or the expression of the cellular changes induced in SK-N-SH cells by neocarzinostatin. PMID- 8363648 TI - Effect of structural modification of alkyl N-propargylamines on the selective inhibition of monoamine oxidase B activity. AB - A series of alkyl N-methyl-propargylamine derivatives has been discovered recently to be very potent selective irreversible monoamine oxidase B inhibitors (MAO-B). In the present study, we used a simple compound in this series, namely N 2-butyl-N-methylpropargylamine.HCl (2-BuMP), as the basic structure to investigate the effect of structural modification on the effectiveness and selectivity of the inhibition of MAO activities. When the N-methyl group was replaced by a hydrogen atom, an ethyl group or a propargyl group, MAO inhibitory activity was abolished. The modification of the propargyl group, e.g. to 3 butynyl, N-cyanomethyl or to allyl groups, also destroyed the inhibitory activity. The potency of the inhibitors was related to the carbon chain length of the alkyl group as well as to the substitution of the alpha or the terminal carbon atoms. Substitution of hydroxyl, carboxyl or carboethoxyl groups on the terminal carbon of the alkyl chain drastically reduced the inhibitory activity. More potent MAO inhibitory activity was observed for molecules with a single methyl group substitution on the alpha carbon in comparison with those substituted with two hydrogen or two methyl groups. Other branched alkyl N methylpropargylamines, e.g. N-methyl-N-(3-pentyl)propargylamine, appeared to be slightly less selective in the inhibition of MAO-B activity. Some of these alkyl propargylamine MAO-B inhibitors, which do not possess the amphetamine-like moiety of L-deprenyl, may have significant neuropsychopharmacological implications. PMID- 8363647 TI - Hepatic disposition of acetaminophen and metabolites. Pharmacokinetic modeling, protein binding and subcellular distribution. AB - Successful pharmacokinetic modeling often requires the ability of a simple model to describe a complex series of physiological processes. However, a simple model may be inappropriate. Physiologically-relevant modeling may offer a more appropriate description, but requires further support from in vitro/in vivo data. A well-stirred hepatic model with linear processes was proposed to describe in vivo disposition of acetaminophen and metabolites after a 100 mg/kg bolus of acetaminophen to vehicle- or phenobarbital-pretreated, renal-ligated rats. Model simulations underpredicted acetaminophen glucuronide (AG) concentrations at early time points in serum, and were inconsistent with AG biliary excretion-rate profiles. Intracellular binding of AG by ligandin was hypothesized, and a cytosolic compartment with reversible binding was incorporated into the model. In this second model, only AG bound in the cytosolic compartment was available for excretion into bile. Model 2 better described the AG biliary excretion rate-time profiles based on calculated Akaike's information criterion values. However, no apparent change was observed in the underprediction of AG serum concentrations. Parameter estimates derived from the two models also were different. The rate constants regulating AG formation and sinusoidal egress were increased significantly after phenobarbital pretreatment according to model 1, while the AG biliary excretion rate constant was decreased significantly. Parameter estimates based on model 2 suggested that phenobarbital pretreatment impaired the cytosolic binding of AG but increased significantly the AG biliary excretion rate constant. The physiologic relevance of model 2 was not supported by a subsequent investigation of the protein binding and subcellular distribution of acetaminophen and metabolites. Acetaminophen, AG and acetaminophen sulfate (AS) were not bound extensively in hepatic cytosol (mean +/- SD unbound fractions were 0.90 +/- 0.08, 0.97 +/- 0.08, and 0.88 +/- 0.06, respectively). Phenobarbital pretreatment did not alter significantly the unbound fractions of acetaminophen, AG or AS in hepatic cytosol. Acetaminophen was distributed to a greater extent in lysosomes than in the nuclear, mitochondrial, microsomal and cytosolic fractions. Distribution of AS predominated in cytosolic and lysosomal fractions. AG was detected only in cytosol. Phenobarbital pretreatment decreased the content of acetaminophen, AG and AS in all hepatic fractions. This study demonstrates the utility of pharmacokinetic modeling in exploring mechanistic hypotheses. However, these results underscore the importance of obtaining pivotal data from in vitro/in vivo studies to validate hypothesized mechanisms. PMID- 8363649 TI - Excretion balance and urinary metabolism of indobufen in rats and mice. AB - The excretion balance and the urinary metabolism of indobufen (+/- 2-[p-(1-oxo-2 isoindolinyl)-phenyl] butyric acid), a platelet aggregation inhibitor, has been studied in rats and mice after oral administration. The urinary metabolic profile of indobufen exhibited a marked species difference. The major metabolic pathway in the mouse was acyl glucuronidation followed by renal excretion, whereas in rats, 5-hydroxylation and subsequent sulphation at the introduced hydroxyl group predominated. Comparison of these results with previous data obtained in humans indicates that the mouse, and not the rat, is the rodent species of choice to be considered in the study of this compound. PMID- 8363650 TI - 2',2'-Difluoro-deoxycytidine (gemcitabine) incorporation into RNA and DNA of tumour cell lines. AB - Gemcitabine (dFdC) is a new cytidine analogue which is active mainly by the incorporation of its triphosphate (dFdCTP) into DNA, leading to cell death. We determined incorporation of dFdC into nucleic acids of two solid tumour cell lines: the murine colon carcinoma cell line Colon 26-10, the human ovarian carcinoma cell line A2780, and the human leukemic cell line CCRF-CEM. dFdC was not only incorporated into DNA, but also into RNA. The extent of incorporation into DNA was highest in A2780 cells and lowest in CCRF-CEM cells (2-4-fold difference). The same pattern was observed for incorporation into RNA, but with a 10-20-fold difference. In A2780, incorporation into DNA was about twice that of the incorporation into RNA, in CEM cells 10-20-fold that of RNA. Incorporation into RNA was verified using two methods for separation of RNA and DNA, acid precipitation and CsCl-gradient centrifugation. Incorporation into DNA was time and concentration dependent, but incorporation into RNA seemed to be only concentration dependent. We also determined the effect of dFdC on DNA and RNA synthesis by measurement of thymidine and uridine incorporation, respectively, using similar conditions as for the incorporation studies. In all three cell lines DNA synthesis was inhibited almost completely, even at 0.1 microM dFdC and at 4-hr exposure. RNA synthesis inhibition did not exceed 50% in both solid tumour cell lines, even at 1 microM dFdC exposure for 24 hr. A clear concentration effect was only observed in the CCRF-CEM cell line and only after 24 hr exposure. At a 1 microM dFdC exposure for 24 hr, RNA synthesis was completely inhibited in these cells. Incorporation of dFdC into RNA and inhibition of RNA synthesis represent an unrecognized but possibly important mechanism of action of this drug. PMID- 8363651 TI - Orally administered prostaglandin E1 derivative can enhance liver regeneration in partially hepatectomized rats. AB - The effect of orally administered 17(S),20-dimethyl-6-oxo prostaglandin E1 (PGE1) methyl ester (OP) on liver regeneration was examined in 66% hepatectomized rats. Administration of OP increased the mitotic index of the hepatocyte 3 days after hepatectomy, and the mitotic index response due to OP was dose dependent. The OP administration had no effect on food intake, but reduced water intake. The serum scores relative to nutrition and hepatic function showed transient change after OP administration, whereas the serum blood urea nitrogen level indicated a slight renal dysfunction with OP. The fat store in the body was transiently reduced. These observations lead us to conclude that orally administered OP is capable of stimulating liver regeneration without serious systemic effects. PMID- 8363652 TI - The effect of 1,4-dihydropyridine and 1,4-dihydroindeno[1,2-b]pyridine derivatives on glutathione S-transferase activity in vitro. AB - The 1,4-dihydropyridine (1,4-DHP) and 1,4-dihydroindeno[1,2-b]pyridine (1,4-DHIP) derivatives were investigated as glutathione S-transferase (GT) inhibitors. The obtained results indicate that some of the 1,4-DHP's containing lipophylic and bulky substituents have inhibitory effects on GT in vitro. The derivatives of 1,4 DHIP are more pronounced inhibitors. PMID- 8363653 TI - [Approach to the study of natural peptides from structure to functions. III. Structural organization of an adrenorphin molecule and its synthetic analogs]. AB - Spatial structure of the peptide hormone adrenorphin was investigated by the theoretical conformational method. A solution of the "reverse conformational problem" for adrenorphin made it possible to predict a series of the modified synthetic analogues, which may assume one of the low-energy conformations of the native hormone. PMID- 8363654 TI - [Cloning the repeat sequence of the oxytocin gene]. AB - Cloning of a synthetic gene of the oxytocin trimer is accompanied by deletions, caused by nicks in the plasmid DNA. Use of covalently closed circular double stranded DNA greatly reduces the number of the deletions. PMID- 8363655 TI - Antenatal diagnosis of Down's syndrome. PMID- 8363656 TI - A recombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice. AB - Since the developmental stages of malarial parasites which replicate within erythrocytes are responsible for the morbidity and mortality associated with this disease, antigens produced by these stages have been proposed as candidates for a vaccine. One surface protein of merozoites (MSP-1) has been shown to immunize both rodents and primates against virulent challenge infection in experimental systems. However, little is known of relevant epitopes on the molecule, and attempts to obtain recombinant MSP-1 polypeptides in a native configuration have proven difficult. We have found that the cysteine-rich, carboxyl-terminal region of the MSP-1 protein from the rodent malarial parasite Plasmodium yoelii yoelii can be expressed in a native configuration as a fusion protein in Escherichia coli. This recombinant polypeptide containing 15 kDa of the predicted 197-kDa protein elicits antibodies in mice which recognize the native parasite MSP-1. Most significantly, both inbred and outbred mice immunized with the fusion protein in Ribi adjuvant are partially and in some cases completely protected against challenge infection with an otherwise lethal parasite strain. This is the first observation of such significant protection obtained with a small portion of the MSP-1 produced in recombinant systems. PMID- 8363657 TI - Medical messages on television. Copycat overdoses coincidental. PMID- 8363658 TI - Better quality data for Down's syndrome register. PMID- 8363659 TI - [Usefulness of electroencephalogram and transcranial Doppler sonography for brain function monitoring during selective cerebral perfusion]. AB - It is well known that neurologic complications greatly affect the postoperative mortality of patients with aortic arch aneurysm. Selective cerebral perfusion (SCP) has been reported to be useful in maintaining cerebral circulation during aortic arch surgery. However, there has been no appropriate method to evaluate brain function during SCP. The purpose of this study was to introduce two new devices, the Lifescan electroencephalogram (EEG) monitor (Neurometrics) and the TC2-64 (EME) transcranial Doppler sonography (TCD), both used for monitoring brain function during SCP in patients undergoing aortic arch surgery. The Lifescan performs aperiodic analysis, and maps each waveform in relation to its frequency, amplitude, and time of occurrence rather than averaging a large number of waveforms over a given period. The Lifescan shows 80% of the whole amplitude of each wave as the activity edge (AE). The flow velocity of the middle cerebral artery was measured by TCD during SCP. With a decrease in body temperature, the EEG and AE gradually showed a trend toward a slower wave and lower amplitude. When circulatory arrest occurred prior to SCP, EEG and AE rapidly showed burst suppression, which was restored after the introduction of SCP. TCD could measure the flow velocity of the left middle cerebral artery even during cardiopulmonary bypass. The flow velocity disappeared during circulatory arrest and was restored after the induction of SCP. It is concluded that the adoption of EEG and TCD is useful in determining the intraoperative cerebral function during SCP. PMID- 8363660 TI - Advanced trauma life support. PMID- 8363661 TI - 12-O-tetradecanoylphorbol-13-acetate and staurosporine induce increased retinoblastoma tumor suppressor gene expression with megakaryocytic differentiation of leukemic cells. AB - The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), induced increased expression of the retinoblastoma (RB) tumor suppressor gene product in the course of megakaryocytic differentiation of the K562 human leukemia cell line, a differentiatively multipotent hematopoietic precursor cell. The induced increase in RB protein per cell occurred early, by 8 h of treatment, preceding any significant phenotypic differentiation evidenced by cellular expression of the CD41 differentiation-specific megakaryocytic cell surface marker, but not inhibition of cell cycle transit, leading to a cell population arrested with 2 n, 4 n, and 8 n DNA content. The increase in RB protein per cell occurred for cells in all cell cycle phases. Staurosporine (STSP) was found to induce a similar course of cell cycle arrest and differentiation. Furthermore, STSP caused an up regulation of RB expression similar to that caused by TPA. Almost all of the RB protein is phosphorylated in untreated cells, but TPA and STSP both caused the late appearance of hypophosphorylated RB protein following cell cycle arrest. The STSP-caused hypophosphorylation was much later than the TPA effect. Hypophosphorylation of RB is, thus, not necessarily a prerequisite for cell cycle arrest but may be a consequence of G0. Given that TPA can be an activator and STSP an inhibitor of protein kinase C, it appears that the induced processes of tumor suppressor gene regulation and growth and differentiation control are not necessarily protein kinase C dependent in K562 cells. Furthermore, the findings that these two presumably divergent inducing agents caused a similar increase in RB gene expression suggests that the up-regulation of RB associated with differentiation is not a coincidence of just one specific inducer but may be a common essential feature of the induced differentiation. The amount of RB protein per cell increased within hours of exposure to TPA or STSP and may have a role in the induced metabolic cascade producing the new phenotype. PMID- 8363662 TI - Women and AIDS. PMID- 8363663 TI - Dental implant care: should it be a specialty? AB - There is a growing demand and need for dental implants, but treatment is reaching only a selected patient population. There is no indication that the profession is unable to meet current needs. The profession must make this care available to more patients, direct preventive measures to susceptible edentate populations and address the issue of entitlement to primary care. PMID- 8363664 TI - Fatal bronchospasm following streptokinase. PMID- 8363665 TI - Why have child pedestrian death rates fallen? AB - Pedestrian injuries are a leading cause of childhood mortality and disability. Over the past two decades in Britain child pedestrian death rates have fallen despite large increases in traffic volume. In this paper Roberts examines the likely reasons for this decline. He argues that neither prevention programmes nor improvements in medical care are a plausible explanation and that the decline is most likely the result of a substantial reduction in children's traffic exposure. He believes, however, that restricting children's traffic exposure exacerbates socioeconomic differentials in childhood mortality and denies children their right to mobility. Roberts is convinced that one answer is for British transport policy to be aimed at providing mobility equitably rather than struggling to meet the ever increasing demands of car travel. PMID- 8363666 TI - Surveillance for gonorrhea and primary and secondary syphilis among adolescents, United States--1981-1991. AB - PROBLEM/CONDITION: During the 1980s, an increasing proportion of adolescent women reported having had premarital sexual intercourse, thus potentially placing an increasing number of young persons at higher risk of acquiring a sexually transmitted infection. REPORTING PERIOD COVERED: To determine rates and examine trends of sexually transmitted infections among adolescents, we analyzed data for reported cases of gonorrhea and primary and secondary syphilis among 10- to 19 year-olds for 1981 through 1991. DESCRIPTION OF SYSTEM: Summary data for cases of gonorrhea and primary and secondary syphilis that were identified and reported to state health departments were sent annually to CDC. These data included total number of cases by disease (gonorrhea, primary and secondary syphilis), sex, racial/ethnic group (white, not of Hispanic origin; black, not of Hispanic origin; Hispanic; Asian/Pacific Islander; or American Indian/Alaskan Native), 5 year age group, and source of report (public, private). RESULTS: From 1981 through 1991, 24%-30% of the reported morbidity from gonorrhea and 10%-12% of the reported morbidity from primary and secondary syphilis in the United States affected the adolescent age groups. Some of the highest rates of gonorrhea during that time period were among 15- to 19-year-olds. Gonorrhea rates among adolescents increased or remained unchanged from 1981 through 1991, while the rates among older age groups decreased. Although primary and secondary syphilis rates were lower among adolescents than older age groups, adolescents contributed to the epidemic of syphilis that occurred from 1987 through 1990. Differences in reported rates of both syphilis and gonorrhea among white, black, and Hispanic adolescents increased during the latter half of the 1980s. INTERPRETATION: Reporting biases could account for some the differences among rates for white, black, and Hispanic adolescents. However, if gonorrhea has been underreported for any racial group, the high rates of gonorrhea among 15- to 19-year-olds represented an underestimate of the true infection rate. Increases in sexual activity among adolescents and a lack of clinical services in settings convenient to adolescents could have contributed to the increasing rates of gonorrhea and syphilis among these young persons during this time period. ACTIONS TAKEN: If gonorrhea and other sexually transmitted infections are cofactors for facilitating the transmission of human immunodeficiency virus (HIV), the high incidence of gonorrhea in some locales among some populations of adolescents could result in dramatic increases in HIV acquisition, a situation that demands attention from public health organizations. PMID- 8363667 TI - [Comparative study of HMB-45 monoclonal antibody uptake on various benign and malignant melanocytic lesions]. AB - In order to evaluate a possible discriminatory diagnosis interest of HMB-45 monoclonal antibody in different melanocytic population, it was tested on 48 benign and malignant melanocytic lesions embedded in paraffin. There were made of 16 benign nevus (33%), 18 dysplastic nevus (38%) and 14 malignant melanomas (29%). The reaction was positive in 11 benign tumors (69%), 18 dysplastic nevus (100%), and 12 malignant melanomas (86%); negative in 5 dermal nevus (31%) and 2 desmoplastic melanomas (14%). We have researched, by the KHI square (chi 2) statistical test, a relation between the reaction intensity, its cutaneous location, and the tumor type. The reaction intensity is not statistically linked with the tumor type. The cutaneous location of the reaction is statistically more heterogeneous in malignant melanoma than in benign or dysplastic melanocytic lesions. Among the dysplastic nevus, 6 cases (38%), of the familial type, have an heterogeneous reaction looking like the malignant melanoma's one. However, there is no significant difference, in the reaction pattern, between dysplastic and benign lesions. Nevertheless some dysplastic nevus seems to have a phenotypic expression for HMB-45 midway between benign and malignant melanocytic lesion, that will be interesting to precise. Otherwise, the simple use and the staining of HMB-45 monoclonal antibody are of great interest to assess the depth of primary cutaneous melanoma and to diagnose secondary melanoma. However, the negativity of the spindle cell type justify the association of other markers, particularly the S100 protein, which is more sensitive, in the diagnosis of desmoplastic malignant melanoma. PMID- 8363669 TI - [Localized osteoplastic bronchopathy with tumoral expression, including Al amyloidosis]. AB - We report a case concerning a 65 year old man who suffered from a drug resistant asthma and radiographically visible mass in the right lower lobe of the lung. Pathological studies demonstrated it to be "Bronchopathia Osteoplastica", involving segmental bronchi, with completed hematopoietic metaplasia. This rare dystrophic lesion was associated with localized lambda light chain amyloidosis as was proved by the immunohistochemistry. This association suggests a possible relation between amyloidosis and abnormal osteogenesis. PMID- 8363668 TI - [Diagnosis of maxillo-facial Burkitt's lymphoma by needle puncture and cytologic examination. Experience in Cameroon]. AB - The authors report their experience on diagnosis of maxillo-facial Burkitt's lymphoma using needle aspiration and cytology. In all the 21 patients presenting a histological proved Burkitt's lymphoma, the diagnosis was done before with cytology. This method has a 100% sensibility. Thus, cytologic diagnosis of maxillo-facial Burkitt's lymphoma is very reliable. In tropical areas with little revenues and where Burkitt's lymphoma is frequent, needle aspiration and cytology need to be well known and used. PMID- 8363670 TI - [Fibroma of the breast. A clinicopathologic study of a case]. AB - Fibromatosis is a fibroblastic proliferation which has infiltrative properties and which is not expected to metastasize. Mammary fibromatosis is infrequent. Clinically, it may mimic breast carcinoma. So, the diagnosis is made from the microscopic examination. Wide local excision is the treatment of choice. But, local recurrence are frequent. PMID- 8363671 TI - [Report of a case of rhabdomyosarcoma of the central nervous system. Histologic, immunohistochemical and ultrastructural study]. AB - A patient, aged 26, had a large parietal tumor, clinically revealed by intracranial hypertension and left sized paresthesia. Removal of tumor was followed by a rapid recurrence. Rhabdomyosarcoma was diagnosed on the second surgical specimen. These tumors are rare in the central nervous system. They occur mostly, though not exclusively, in young adults. Their prognosis is poor and their histogenesis is still unclear. PMID- 8363672 TI - [A cutaneous parasitosis rarely observed in France: chromomycosis]. AB - The authors report a case of chromomycosis presenting like a tumoral lesion in a patient coming from the Isle de Mayotte. The causative agent is Fonsecaea pedrosoi. The evolution was favorable after surgical treatment. The epidemiology, the histopathological features, the diagnosis problems and the evolution of the illness are studied. PMID- 8363673 TI - [Histopathologic lesions in erythromelalgia during essential thrombocythemia]. AB - Erythromelalgia is a vascular disorder of the extremities and is sometimes related to myeloproliferative syndrome with thrombocythemia. We report the cutaneous histopathology in case of erythromelalgia that revealed a thrombocythemia vera. Small arteries were occluded by thrombi of different age and narrowing of the lumen occurred by intimal proliferation of smooth muscle cells. There was no involvement of venules or capillaries. These vascular changes are highly suggestive of erythromelalgia and have not to be confused with necrotizing and/or granulomatous angiitis because of absence of fibrinoid necrosis and sparse inflammatory cells. PMID- 8363674 TI - [Autopsy protocol in the sudden infant death syndrome (SIDS)]. PMID- 8363675 TI - [Malacoplakia of the breast]. PMID- 8363676 TI - [A skin eruption 10 years after a trip to Haute-Volta]. PMID- 8363677 TI - [Askin's tumor: a clinicopathologic entity?]. PMID- 8363678 TI - [Polymerase chain reaction (PCR) and pathology. Technical principles and application]. PMID- 8363679 TI - The role of single ECG, creatinine kinase, and CKMB in diagnosing patients with acute chest pain. AB - The objective of this study was to determine the combined accuracy of emergency department (ED) cardiac enzymes and electrocardiograms (ECGs) in patients who were admitted to "rule-out" myocardial infarction (ROMI). A retrospective analysis of ED creatinine kinase (CK), CKMB, and ECG was performed and the results were compared with final hospital diagnosis of MI, in the ED of a medical school- and university hospital-affiliated teaching Veterans Affairs Medical Center. Approximately 222 consecutive ED patients admitted to ROMI, including 43 (19%) MI patients, 29 (67%) of whom presented to the ED within 24 hours of symptom onset were eligible to participate. Interventions included an analysis of CK and CKMB results and ECG findings. There were no statistical differences in the sensitivities, specificities, and predictive values when the two cardiac enzymes were compared. Almost all of the elevated cardiac enzyme results occurred in MI patients who presented within 24 hours of symptom onset, more than half of whom had ED cardiac enzyme elevations. For all MI patients, regardless of duration of symptoms, more than half of the ED ECGs had new ST-T changes consistent with an acute MI or acute myocardial ischemia. In the MI patients who presented within 24 hours of symptom onset, 79% had positive enzymes or ECG or both in the ED. No statistically significant difference in the sensitivity rates for MI between the CK and CKMB comparing enzymes with ECGs was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363680 TI - Effect of extreme temperatures on drugs for prehospital ACLS. AB - Advanced cardiac life support drugs undergo a wide range of temperature exposures in the prehospital setting. Although manufacturers place temperature restrictions for drug stability on their products, it has been shown that these limits are often exceeded in the prehospital environment. We exposed four different drugs to temperatures of -20 degrees C (-6 degrees F) and 70 degrees C (150 degrees F) and subsequently performed assays to determine their respective chemical stability compared with that of control samples. We determined that no significant difference in chemical structure occurred between the standard sample and the four drugs exposed to extreme temperatures (P > .05). This information has obvious implications in making further recommendations for drug storage. More work to determine bioactivity of temperature-exposed drugs may show results with implications for success in prehospital cardiac resuscitation. PMID- 8363681 TI - Oral labetalol versus oral nifedipine in hypertensive urgencies in the ED. AB - Therapy in hypertensive urgencies is debated and complicated by the side effects of available agents. In a prospective, randomized, open labeled study, the use of oral labetalol, an alpha- and beta-adrenergic blocker, with oral nifedipine in hypertensive urgencies in the emergency department was compared. Patients with diastolic blood pressures (DBP) of more than 120 mm Hg without criteria for a hypertensive emergency were eligible. The drugs were given in a loading manner with doses and timing based on their respective pharmacokinetics until a DBP of 110 mm Hg or lower was obtained or 4 hours had passed. Either an initial labetalol dose of 200 mg and a repeat dose of 100 to 200 mg at 2 hours, depending on the DBP or nifedipine, 10-mg bite and swallow every hour up to a total dose of 20 mg were given. Ten patients were enrolled into each study group. A 100% response rate was defined as a DBP of 110 mm Hg or less was observed for nifedipine and an 80% response rate for labetalol (P > .2) was observed. The mean time to control was 67.5 minutes for labetalol and 60.0 minutes for nifedipine (P > .2). The pretreatment pressure for labetalol was 195/127 mm Hg and for nifedipine was 198/128 mm Hg (P > .2), which decreased to a posttreatment pressure for labetalol of 154/100 mm Hg and for nifedipine of 163/100 mm Hg (P > .2). The mean decrease in systolic (SBP)/DBP was 42.6/26.5 mm Hg with labetalol and 34.9/28.4 mm Hg for nifedipine (P > .2). No significant side effects occurred with either drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363682 TI - The effect of a class IV hurricane on emergency department operations. AB - The objective of this study was to determine the impact on emergency department (ED) operations of Hurricane Hugo, a class IV hurricane that struck Charleston, South Carolina, on September 21, 1989. The study design was a retrospective record-based descriptive study and mail survey of the ED of a 300-bed regional medical center directly in the path of the storm. During the 3 weeks after the storm, ED patient volume increased 19% over that of the 3 weeks before the storm. Increased visit volumes were evident for at least 3 months. Compared with a similar period of the previous year, there was an increase in the proportion of patients seen for lacerations of all types, puncture wounds, stings, and falls. Sixty-two percent of physician offices were still closed 7 days after the storm. The direct effects of a class IV hurricane on ED operations included major alterations in the volume and types of patient visits. Because of the evacuation of approximately 40% of the coastal population and storm damage hindering travel, the increase in visit volume was less in magnitude but of longer duration has been reported in class III hurricanes. PMID- 8363683 TI - Lupus patients with peripheral vascular thrombosis: the significance of measuring anticardiolipin antibody. AB - The purpose of this study was to determine the significance of measuring anticardiolipin (ACL) antibodies in Chinese lupus patients with peripheral vascular thrombosis. A total of 252 lupus patients were evaluated prospectively for the presence of peripheral vascular thrombosis in a 3-year period. Tests of ACL antibodies with three isotypes were done serially during follow-up. There were 10 lupus patients with five episodes of arterial thrombosis and seven episodes of venous thrombosis by the evidence of angiographical and/or pathological findings. The ACL antibody status was negative (< 2 standard deviation [SD]), low (2 to 5 SD) and high (> 5 SD) for 43.3%, 22.6%, and 34.1% patients, respectively. Patients with high levels (> 5 SD) of ACL antibodies had a high frequency of peripheral vascular thrombosis than patients with negative levels (> 2 SD) of ACL antibodies (P < .05). It is concluded that serial measurement of ACL antibodies in lupus patients is useful in predicting the occurrence of peripheral vascular thrombosis. Clinicians should be alert to the possibility of such complication in lupus patients with high ACL antibodies levels when visiting the emergency service. PMID- 8363684 TI - Infantile methemoglobinemia associated with acute diarrheal illness. AB - A case of an infant with diarrhea and acidosis associated with methemoglobinemia is presented. Of interest is that the association of diarrhea and acidosis with methemoglobinemia is more common than previously thought and can produce dangerously high methemoglobin levels. A review of the literature of this unusual occurrence along with clues to making the diagnosis are discussed. PMID- 8363685 TI - Isolated jejunal perforation from nonpenetrating abdominal trauma. AB - Although jejunal perforation from blunt trauma is a common injury, isolated jejunal perforation is an uncommon entity. A case of isolated jejunal perforation from blunt trauma is presented. This case showed that symptoms and physical findings from jejunal perforation may be minimal. The use of various diagnostic procedures, such as chest radiograph for free air, diagnostic peritoneal lavage, or abdominal computed tomography for diagnosing intestinal perforation were reviewed. Serial abdominal examination continued to be paramount in diagnosing intestinal injuries. Sufficient vigilance and suspicions of small bowel perforation should always be considered after blunt trauma even when symptoms and physical findings are minimal. PMID- 8363686 TI - Acute suppurative salpingitis with concomitant intrauterine pregnancy. AB - A 20-year-old woman presented to the emergency department with a history of lower abdominal pain and recent loss of consciousness. She was admitted with a primary diagnosis of abdominal pain; ectopic pregnancy was ruled out. The culture of the endocervix was positive for Neisseria gonorrhoeae. Surgical exploration of the pelvis was performed, and histological analysis of the specimen showed an acute suppurative salpingitis and an intrauterine pregnancy. The patient was placed on intravenous antibiotics. Postoperative course was unremarkable, and the patient was discharged on oral antibiotics. Although a rare entity acute suppurative salpingitis with concomitant intrauterine pregnancy are not mutually exclusive. Ectopic pregnancy should be the presumptive diagnosis when clinical presentation is consistent with pelvic inflammatory disease and pregnancy especially in the first trimester. Patients who are pregnant and exhibit clinical signs and symptoms that are consistent with salpingitis should be admitted for aggressive management of their high-risk pregnancy. Fetal wastage seems to be significant in spite of aggressive management. Endocervical culture for N gonorrhoeae should be obtained from all pregnant patients with follow-up treatment pending culture results. The following is a case presentation along with a review of the existing cases in the English literature and discussion of the possible pathogenesis and clinical outcome of this entity. PMID- 8363687 TI - Ruptured ectopic pregnancy after medical management: current conservative management strategies. AB - A case of hypotension caused by hemorrhage in a patient receiving systemic methotrexate to treat a known ectopic pregnancy is presented. A primary goal of gynecologic practice in the 1990s is to conserve tubal patency and fertility. Consequently, ectopic pregnancy is more frequently being managed by conservative strategies. The emergency physician must be familiar with conservative methods for the management of ectopic pregnancy and the complications that may cause emergency presentations in these patients. PMID- 8363689 TI - Cases in electrocardiography. PMID- 8363688 TI - The shorthand vertical mattress stitch: evaluation of a new suture technique. AB - The shorthand vertical mattress suture is a new suture technique that provides the same amount of wound eversion in less time than the classic method. A randomized, prospective clinical trial was designed to test this hypothesis in a University-affiliated community hospital. Thirty patients who presented to the emergency department with traumatic lacerations requiring primary closure were eligible for this study. Wounds involving the hands, feet, or face were excluded. Patients meeting inclusion criteria were allocated randomly to have either shorthand or classic vertical mattress sutures. Wound information was collected on data sheets and included physician training level, repair time, number of knots placed, and degree of wound-edge eversion for each suture technique. Subjects were then asked to return to the emergency department in 7 to 10 days for wound assessment and suture removal. Thirty-six lacerations to the scalp, trunk, and extremities were evaluated. Shorthand vertical mattress sutures were used on 20 wounds (56%) and classic mattress sutures were used on 16 (44%) wounds. The shorthand stitch provided the same amount of wound eversion in half the time as the classic technique. No infectious complications, delayed wound healing, or cosmetic problems were observed with the shorthand technique. The shorthand vertical mattress stitch described is an efficient, alternative method for laceration repair without compromising wound eversion or cosmetic results. PMID- 8363690 TI - Humanism in emergency medicine. AB - Emergency medicine has not yet appropriated "humanism" as a term of its own. Medical humanism needs to be interpreted in a way that is consistent with the practical goals of emergency medicine. In this essay, humanism in emergency medicine is defined by identifying the dehumanizing aspects of sudden illness and exploring of ways for sustaining the humanity of emergency department patients. Excerpts from Dr Oliver Sacks' autobiographical work A Leg to Stand On give voice to the human needs created by sudden illness and its treatment. PMID- 8363691 TI - Acute hemolytic anemia after ingestion of fava beans. PMID- 8363692 TI - Corneal abrasions secondary to activated charcoal. PMID- 8363693 TI - The case for lateral stiffness in walking orthoses for paraplegic patients. AB - The provision of walking for paraplegic patients has therapeutic benefits but must be at a low energy cost. Although claims have been made regarding the need for high lateral stiffness in any orthosis targeted at this group, much of the supporting evidence was confusing. This paper presents the theoretical reasoning behind this claim and reviews recent evidence that would appear to support it. PMID- 8363694 TI - Pressurization of bone cement under standard, flanged and custom acetabular components for total hip replacement. AB - Custom acetabular components are proposed to achieve uniform cement mantles, even in irregular acetabula presented at revision, in order to enhance fixation. One aim of developing custom components was to permit pressurization of bone cement by the components at insertion and maintain the pressure during polymerization. A model acetabulum was set up for the insertion of standard, flanged and custom components under constant force. Cement pressure was measured at the floor of the acetabulum by means of a piezoelectric diaphragm transducer. Polythene tubes were inserted in the model acetabular walls to estimate penetration of cement into cancellous bone. Insertion of the standard and flanged components caused cement pressures up to 106 kPa which decayed to less than 21 kPa as cement escaped at the rim and the components came into contact with the acetabulum. The custom component maintained a pressure of over 60 kPa during polymerization from an initial pressure of 105 kPa and examination of cement mantles on removal showed no evidence of contact. The custom component also showed enhanced penetration of cement, especially around the rim of the acetabulum. It is concluded that the custom component design achieves higher cement pressures and that better fixation will result. PMID- 8363695 TI - Friction and lubrication in cushion form bearings for artificial hip joints. AB - Two hip joint prostheses were designed and constructed to be elastohydrodynamically equivalent producing approximately equal initial contact areas and theoretical film thicknesses. One was made from conventional UHMWPE (ultra-high molecular weight polyethylene) and the other was a cushion component which had a low modulus layer introduced into the joint space. Friction measurements were carried out on a pendulum simulator apparatus and the two joints were compared. In addition the experimental results were compared with theoretical values of friction predicted from elastohydrodynamic lubrication theory. Values for the friction factor at peak load and peak velocity in the cushion cup (0.003-0.009) were much lower than in the UHMWPE cup (0.017-0.042). The low friction values in the cushion cup are consistent with fluid film lubrication in the contact with the thin lubricating film being preserved by microelastohydrodynamic action. PMID- 8363696 TI - Load concentrations around crystal aggregates in articular cartilage under short term loading. AB - The deposition of crystals in joints is a feature of a number of joint diseases. Crystals are frequently observed on the surface of articular cartilage and in the mid-zone. The purpose of this investigation was to model the stress concentrations in the mid-zone of the cartilage layer arising from the presence of large crystal aggregates. Scanning electron microscopy was used to determine the geometry and distribution of crystal aggregates within the cartilage layer. Finite element and photoelastic approaches were then used to predict the stress distribution around spherical aggregates 50 and 100 microns in diameter. The implication of the results is that very densely packed and tightly bound spherical aggregates will themselves carry a certain amount of load. However, less tightly packed aggregates, perhaps interspersed with fibrous tissue, are potentially much more damaging. PMID- 8363697 TI - Wear of articular cartilage: the effect of crystals. AB - An investigation of the effect of crystals in a lubricant on the wear of articular cartilage in vitro was carried out in order to examine the hypothesis that crystals present in synovial fluid could cause abrasive damage of the articular surface. Plugs of cartilage were worn against a stainless steel counterface in a pin-on-disc wear rig. The concentration of cartilage debris present in the lubricant was assessed by measuring the bound sulphate originating from the glycosaminoglycans by ion chromatography. Results indicated that the presence of crystals in the lubricant significantly increased the concentration of wear debris and that the crystal size and morphology influenced the type of damage sustained by the cartilage. Other experimental evidence suggested that cartilage scratched in vivo was no more susceptible to further in vitro damage in this experimental model than normal cartilage. These results implied that crystals present in the synovial fluid of arthritic joints have the potential to cause excessive wear of the articular surface, but that if such crystals are removed the scratched cartilage may not be susceptible to any further damage by abrasive wear. PMID- 8363698 TI - Sliding friction analysis of phosphatidylcholine as a boundary lubricant for articular cartilage. AB - Dipalmitoyl phosphatidylcholine (DPPC), the major lipidic component of the synovial fluid (45 per cent), has been implicated in previous studies in synovial joint lubrication as a potential boundary lubricant for articular cartilage. The purpose of this study was to evaluate the effectiveness of DPPC as a boundary lubricant at physiological stresses experienced by weight-bearing joints (up to 7.5 MPa). The sliding coefficients of static and kinetic friction for glass surfaces coated with DPPC layers of physiological thickness (70 nm) were measured as a function of average contact stress, contact geometry (point and line), applied load and relative velocity (from 25 to 0 mm/s) and compared to the coefficient of friction for clean glass in the same conditions. The coefficient of friction for DPPC-lubricated surfaces was dependent on contact geometry, obeyed Amonton's law (not dependent on axial load or contact area), was dependent on relative velocity within the range stated and was an effective lubricant at physiological stresses. This study showed that dipalmitoyl phosphatidylcholine can be an effective boundary lubricant at stresses observed in load-bearing joints. Because of their surface-active nature, these adsorbed molecules might also act as a protective layer for the articular surfaces. PMID- 8363699 TI - Ligament forces at the knee during isometric quadriceps contractions. AB - A mathematical model of the knee in the sagittal plane was used to investigate the ligament forces resulting when a posteriorly directed external force, applied to the tibia, resists extension of the knee under increasing isometric quadriceps contractions. The model is based on simple geometric representations of the bones, ligaments and muscles at the knee. An elementary mechanical analysis was used to predict which ligament, the anterior or posterior cruciate, was loaded at a given flexion angle and known line of action of the external force. Ligament force, as a proportion of the external force, was calculated first assuming the ligaments to be represented by single, inextensible lines. Modelling the ligaments as continuous arrays of extensible fibres then showed that tibio femoral translations and ligament forces increased non-linearly with increasing muscle forces and approached asymptotic values which depended on flexion angle. In most positions of the joint, the calculated asymptotic ligament force values were less than the reported ultimate strength of human ligament, despite quadriceps forces of over three times body weight. The possibility of these asymptotic values of ligament force may explain why, at certain flexion angles, large forces can be developed by the muscles at the knee without ligament rupture. PMID- 8363700 TI - Application of 2D 1H NMR spectroscopy to the study of the brain, spinal cord, and sciatic nerve. AB - Homonuclear 1H 2D NMR spectroscopy (COSY experiments at 400 and 600 MHz) were used to study the rat brain in vivo and the rabbit spinal cord and sciatic nerve in vitro. The following metabolites were identified: lactate, alanine, threonine, GABA, glutamine/glutamate, N-acetyl aspartate, aspartate, taurine, inositol derivatives, choline derivatives, and glucose. The sciatic nerve spectra showed characteristic COSY graphs of saturated and unsaturated fatty acids, and linoleic and linolenic type structures were identified. PMID- 8363701 TI - Dopamine receptors status after unilateral nigral 6-OHDA lesion. Autoradiographic and in situ hybridization study in the rat brain. AB - The physiological effects of dopamine (DA) are mediated by several distinct receptor subtypes. The effects of unilateral nigral 6-hydroxydopamine (6-OHDA) lesions on DA receptors were investigated by receptor autoradiography using the D1 selective ligand [3H]SCH 23390 as well as the D2 ligand [3H]spiroperidol. mRNA distribution was studied by in situ hybridization. Lesioned rats were sacrificed at different time intervals. Receptor binding studies were performed on tissue sections using selective ligands. [35S]UTP labeled RNA probes were prepared from the different cDNA (D1, D2, D3) and used for in situ hybridization. A specific loss of receptor binding sites and mRNA hybridization was found in the lesioned substantia nigra pars compacta (SNc) at all times examined. Receptor binding studies revealed a different time-dependent increase in both D1 and D2 receptors. In situ hybridization showed that only D2 receptor mRNA increased in the caudate putamen (CPu) of the lesioned side 15 d after 6-OHDA. No changes were observed in D1 and D3 receptor mRNA during the entire time-course. PMID- 8363702 TI - The value of transcranial Doppler sonography in the differential diagnosis of Alzheimer disease vs multi-infarct dementia. AB - Primary degenerative dementia of the Alzheimer type and multi-infarct dementia exhibit differences in cerebrovascular blood flow velocity profiles, which were investigated by means of transcranial Doppler sonography. The pulsatility indices, as angle-independent parameters of peripheral vascular resistance, measured in middle cerebral and basilar arteries of patients with multi-infarct dementia (MID), were significantly increased (p < 0.005) with respect to cases of primary degenerative dementia of the Alzheimer type and to healthy age-matched controls. Approximately 75% of all MID patients exhibited small vessel disease rather than thromboembolism from the extracranial arteries and the heart, as judged by extracranial and transcranial Doppler sonographies, computerized cerebral tomographies, EEGs, and, if necessary, 2-D echocardiographies. PMID- 8363703 TI - Natural histidine-containing dipeptide carnosine as a potent hydrophilic antioxidant with membrane stabilizing function. A biomedical aspect. AB - A review on the distribution and biological effects of carnosine and a hypothesis for its biological mechanisms of action are presented. Carnosine and its structural and functional relative, anserine, were found in skeletal muscles at the beginning of the century. Their effects on muscle-working capacity, on the stability of membrane-bound enzymes, as well as their potent immunomodulating property, could not be explained by their pH-buffering capacity or formation of the secondary metabolites histidine and beta-alanine alone. This article suggests that the basis for the biological activities of carnosine and relative compounds is their potent antioxidant and membrane-protecting activity. The plausible chemical mechanism of this activity is discussed, and data regarding the usage of carnosine as a drug for treatment of immunodeficiency are summarized. PMID- 8363704 TI - The role of the active site amino acid residues on the catalytic activity of Cu2Zn2SOD. AB - Copper, zinc superoxide dismutase, the enzyme that catalyzes the dismutation of the superoxide ion, is a key enzyme for neurodegenerative processes caused by the formation into tissues of this reactive free radical. Although the structure of enzyme is known, the catalytic mechanism has not yet fully elucidated. The copper ion represents the center, which exchanges electrons with the superoxide ion, but other residues present in the active site seem to play a relevant role. The most recent advancements in clarifying the structure-function relationship in this enzyme are discussed. PMID- 8363705 TI - Membrane lipid degradation during ischemia and impact on the monolayer surface pressure area diagram (SPAD). AB - This article briefly reviews the importance and relevance of membrane lipid degradation to the pathogenesis of ischemic brain damage ranging from the liberation and accumulation of free fatty acids (FFA) to their consequences on the biophysical characteristics of membrane lipids. The rapid accumulation of brain FFA during cerebral ischemia is a hallmark of the evolution and pathogenesis of ischemic brain damage: It signals the degradation of membrane lipids; it generates the precursors to the metabolically and physiologically potent eicosanoids; and it promotes the generation of lipid oxidizing free radicals, which could propagate the destruction of membrane lipids. The impact of ischemia-induced changes in cerebral membrane lipid composition on membrane function is difficult to assess in vivo. Some estimate of the impact of the changes, however, can be obtained by evaluating the changes induced in the surface pressure-area diagrams (SPAD) of membrane lipid monolayers at the air water interface. Lipid monolayers are used as model membranes to study the effects of lipid composition on the biophysical behavior of membrane lipids and their interaction. Regional brain lipids were quantitated at different times during ischemia, and their impact on their surface pressure area diagrams was assessed and their potential impact on membrane function discussed. PMID- 8363706 TI - Evidence for a membrane lipid defect in Alzheimer disease. AB - We have previously shown that cells normally maintain their lipid metabolic pools at a critical composition, appropriate for spontaneous assembly of a stable membrane bilayer at their physiological temperature. When disease affects membrane lipids such that the new composition will only form a stable bilayer at a critical temperature (T*), which differs from the physiological value, membrane destabilization and hence cellular damage will necessarily ensue. We have previously tested this pathogenetic mechanism in metachromatic leukodystrophy, a disorder with a known primary lipid metabolic defect. In the present study, we found T* for cerebral cortex lipids from three Alzheimer disease (AD) patients ranged between 19 and 28 degrees C, independent of membrane protein composition. Control cortex lipids yielded a normal value for T* of 37 degrees C. Thus, one possible mechanism for neurodegeneration in AD is membrane destabilization secondary to a lipid compositional aberration, which shifts T* away from 37 degrees C. This lipid defect is brain region-specific as cerebellar lipids from the AD patients gave a normal value for T*. Studies aimed at delineating the nature of the biochemical anomaly are in progress. PMID- 8363707 TI - Inflammation and the brain. AB - Inflammation in the brain selectively damages the myelin sheath resulting in a variety of clinical syndromes of which the most common is multiple sclerosis. In these disorders, the areas of inflammation and demyelination can be identified in life by magnetic resonance imaging. Events occurring at the blood-brain barrier depend on T-cell activation, which increases immune surveillance within the central nervous system. T-cells activated against brain antigens persist to establish the conditions needed for inflammatory demyelination and this depends on local release of cytokines, culminating in removal of oligodendrocytes and their myelin lamellae by macrophages or microglia. These interactions involve binding between receptors present on microglia for the Fc portion of antibody and complement components to corresponding ligands on target cells. Taken together, the evidence from clinical and experimental studies provides a rationale for the issue of immunological treatments in patients with multiple sclerosis. PMID- 8363708 TI - Mechanisms of hypoxic and ischemic injury. Use of cell culture models. AB - Cell cultures are useful tools to study the mechanisms involved in cell death following hypoxia or ischemia. By manipulating the extracellular environment, conditions that closely mimic the conditions that are thought to occur in vivo can be produced. These conditions permit study of cell's reaction to the trauma under specific conditions. Monitoring of the extracellular pH and ionic environment in cell cultures is much easier than in vivo. Further, metabolites produced by injured cells can be quantitated easier from cultures than from tissues in vivo. Cell cultures have recently been used to examine in detail the neurotoxicity of glutamate. Intracellular Ca2+ increases appear to be involved in the mechanisms of neurotoxic cell death. This Ca2+ entry appears to be through the NMDA receptor's Ca2+ channel. Ischemic and hypoxic injury produced by mechanisms other than glutamate neurotoxicity appear to involve increases in intracellular Ca2+ by releasing internal Ca2+ stores or by the influx of extracellular Ca2+. This Ca2+ entry may be through voltage-gated channels of the NMDA channel, or may be attributable to membrane perturbations. Through the use of cell cultures, each of the mechanism's involvement in the injury can be delineated. PMID- 8363709 TI - Pseudoverdin, a compound related to the pyoverdin chromophore from a Pseudomonas aeruginosa strain incapable to produce pyoverdins. AB - From a genetically manipulated strain of Pseudomonas aeruginosa ATCC 15692 (PAO1 strain) a compound named pseudoverdin, 3-formylamino-6,7-dihydroxycoumarin, was obtained which is related to the typical pyoverdin chromophore and thus allows to shed some light on the biogenesis of the latter. PMID- 8363710 TI - Azadirachtin inhibits proliferation of Sf 9 cells in monolayer culture. AB - Azadirachtin A in ppm quantity inhibits proliferation and monolayer formation of Spodoptera frugiperda (Sf9) insect cells in monolayer culture. The incubated cells demonstrate reduced rates of protein synthesis which finally leads to cell death. This growth inhibiting activity is compared with other botanicals such as ohchinin, salannin and volkensin. The high and specific activity of azadirachtin A on insect cells is discussed in comparison with its effect on a mammalian cell line, based on 2 D PAGE analysis of the total protein contents. PMID- 8363711 TI - Inter- and intraspecific variation of the nucleotide sequence of the cytochrome b gene in Cory's (Calonectris diomedea), Manx Shearwater (Puffinus puffinus) and the Fulmar (Fulmarus glacialis). AB - The cytochrome b gene of three European taxa of the family of Procellariidae was amplified from total DNA and sequenced. The sequence comparison shows that the Fulmar (Fulmarus glacialis) is significantly distinct from shearwaters, whereas Cory's (Calonectris diomedea) and Manx Shearwater (Puffinus puffinus) are closely related. Although the populations of C. diomedea can be distinguished morphologically, the sequences of cyt b differ only slightly between the Atlantic and Mediterranean subspecies (i.e. C. d. borealis versus C. d. diomedea) and do not reveal other population differences within subspecies. PMID- 8363713 TI - [Autopsy-confirmed nosocomial infections among the deaths in an intensive care unit]. AB - In a 6-year retrospective study the occurrence of autopsy-confirmed nosocomial infections in 282 deceased patients of an intensive care unit was investigated. The autopsy rate was 100%. In 107 deceased (37.9%) 126 nosocomial infections were confirmed. The most common nosocomial infection was bronchopneumonia (54%). The main ailment was non-tumorous diseases of the digestive system (43.9%). In nearly 60% of the 107 deaths, nosocomial infections were the immediate cause of death. In all 282 deceased, hospital infections were the direct cause of death in 22.7% of these cases. The study emphasizes the importance of nosocomial infections as a causal or contributory factor in the death of patients in an intensive care unit. PMID- 8363712 TI - [Should the use of succinylcholine in pediatric anesthesia be re-evaluated?]. AB - We report on the occurrence of cardiac arrests within a few minutes following succinylcholine in 9 children, all of whom were later shown to have occult neuromuscular disease. Five of the children did not survive the catastrophic event. The anaesthetist in most cases, when discussing premedication, got the impression that the patients were in good health; just in 2 children were there indications of myopathy. Myopathic children coming to surgery and anaesthesia are rare. In these cases the administration of succinylcholine is contraindicated. But the anaesthetist must be aware of the fact that a small number of paediatric patients with unknown/subclinical myopathies might be referred to him. In these cases, without warning muscle rigor, bradycardia and hyperkalemia cardiac arrest may develop within minutes following administration of succinylcholine. The anaesthetist must be prepared for such a challenging event--particularly mentally. Misinterpretation of the symptoms as signs of malignant hyperthermia should be excluded. Resuscitation must start without delay and must continue for more than 30 minutes. Therapeutic attempts to lower extracellular potassium with glucose and insulin must fail for pharmacokinetic reasons. Therapy with intravenous calcium under control of the e.c.g. seems to be the only rational approach to the problem. It is suggested that in every healthy child coming to anaesthesia the physician should consider whether relaxation could not be achieved by other agents. Succinylcholine may well be defined as a "membrane poison"--especially considering the efflux of potassium, myoglobin and creatine kinase from the intracellular space into the bloodstream. The answer to the question asked in the title must therefore be: definitely--yes. PMID- 8363714 TI - [Intraoperative cardiopulmonary disorders during esophagectomy in relation to the surgical technique]. AB - Twenty-one healthy female sheep were anaesthetised in a standard technique with ketamine, dehydrobenzperidol and etomidate. In seven sheep an endoscopic esophagectomy was made (group 1), in seven a blunt esophagectomy (group 2) and in a further seven a thoraco-abdominal esophagectomy (group 3). ECG monitoring, invasive blood pressure measurement, measurement of the central venous pressure and the pulmonary artery pressure with estimation of cardiac output, arterial and mixed venous blood gas analyses were made. The measurement times were: ZDM 1 = preoperative, ZDM 2 = after laparotomy, ZDM 3 = after cervical esophagus preparation or thoracotomy, ZDM 4 = after esophagectomy, ZDM 5 = after inflation of the lungs and ZDM 6 = after a second exploration of the esophagus bed (only groups 1 and 2). Finally the sheep in groups 1 and 2 were thoracotomised on the right side. In group 1 the measurement parameters remained largely unchanged during the entire experiment. In group 2 significant and by the end of the operation irreversible pathological changes occurred immediately after the blunt esophagus resection (ZDM 4): decrease of MAP, paO2 and CO, increase of AaDO2 and PVR. In group 3 similar changes were observed, they began, however, during ZDM 3. The measurement results can be explained in accordance with the operative anatomical findings. How far postoperative pulmonary complications can be avoided in patients with the endoscopic technique must be demonstrated in clinical use. PMID- 8363715 TI - The use of an assessment tool in managing placement on pressure relief surfaces. PMID- 8363716 TI - A pressure ulcer prevention program. AB - The prevention and management of pressure ulcers often creates challenging situations requiring specialized knowledge and expert, consistent nursing care. In order to promote pressure ulcer prevention and control costs at a 350-bed community hospital, a "Pressure Ulcer Prevention Program" was developed. This program was developed upon completion of a baseline audit determining the extent of skin problems, equipment in use, and nursing documentation regarding skin care. Five months after initiation of the program, a second audit was conducted to evaluate the effectiveness of the program. An overall decrease in pressure ulcer incidence was found and the documentation of pressure ulcer prevention was improved. PMID- 8363717 TI - Clinical validation of pressure ulcer risk factors. AB - The maintenance of skin integrity is considered to be a survival need in the human need nursing framework. Risk factors for the nursing diagnosis High Risk For Impaired Skin Integrity: Pressure Ulcer were identified in a diagnostic content validity study. The purpose of this study was to use a pressure ulcer risk assessment instrument based on results of that study. The clinical validation model was used to analyze the ulcer risk factor cluster present in a sample of older adults residing in two nursing homes in the Mid-Atlantic region of the United States. A convenience sample of 108 residents were each assessed independently by two research assistants. Interrater reliability of the instrument was 93 percent. There were eight risk factors present in more than 60 percent of the subjects in the pressure ulcer group; six in the high risk group, and five in the low risk group. Findings suggest that three factors may be the best discriminators for pressure ulcer risk: (1) friction, (2) being dependent in self-care, and (3) being confined to bed/chair. PMID- 8363718 TI - The process and criteria for national coverage decisions by HCFA's Medicare program. Excerpted from an oral presentation delivered by Dr. Sam Shekar. PMID- 8363719 TI - Veridien expects FDA approval soon on HIV virus-killing Sterihol. PMID- 8363720 TI - O/WM board members are invited to peer review AHCPR draft of literature review summary on dressings. PMID- 8363721 TI - Activation-induced cell death (apoptosis) of mature peripheral T lymphocytes. AB - Programmed cell death (apoptosis) is triggered in immature thymocytes and T-cell hybridomas by signalling via the CD3-T-cell receptor pathway. In this paper, Dieter Kabelitz and colleagues catalogue the recently accumulating evidence that apoptosis can also be initiated in mature peripheral T cells; this may constitute an important aspect of cellular immune regulation. PMID- 8363722 TI - Antigen presentation, loss of immunological memory and AIDS. AB - A key factor causing immunodeficiency in HIV infection seems to be defective antigen presentation. Consequently, CD4+ T-cell populations, initially those expressing CD45RO, decrease in number not because of their destruction, but because they fail to expand in response to antigenic stimulation. This view implies that it would be mistaken to aim therapies only at correcting T-cell function or preventing infection of T cells. PMID- 8363723 TI - Can soluble antigens induce CD8+ cytotoxic T-cell responses? A paradox revisited. AB - Cytotoxic T lymphocyte (CTL) induction usually follows processing of antigens via endogenous pathways before presentation on the cell surface in association with MHC class I molecules. Soluble antigens do not, in general, induce specific CTL responses. Here, Syamal Raychaudhuri and John Morrow suggest that a novel adjuvant formulation can elicit CTL responses to soluble antigens and discuss the implications for vaccine development. PMID- 8363724 TI - Map of the human MHC. PMID- 8363725 TI - Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? AB - Pregnant females are susceptible to intracellular pathogens and are biased towards humoral rather than cell-mediated immunity. Since TH1 cytokines compromise pregnancy and TH2 cytokines are produced at the maternal-fetal interface, we hypothesize that these TH2 cytokines inhibit TH1 responses, improving fetal survival but impairing responses against some pathogens. PMID- 8363726 TI - Signal transduction events leading to T-cell lymphokine gene expression. AB - The expression of T-cell derived lymphokines is regulated by signal transduction events initiated by the T-cell antigen receptor and other T-cell surface molecules. Substantial progress has been made in characterizing the signal transduction events initiated at the plasma membrane of the T cell and their targets which control lymphokine gene expression in the nucleus. This review will summarize recent progress in this area of investigation. PMID- 8363727 TI - Myasthenia gravis: recognition of a human autoantigen at the molecular level. AB - The symptoms of myasthenia gravis are primarily or exclusively due to an autoimmune response against the muscle nicotinic acetylcholine receptor (AChR) and this has been the object of intensive investigations for almost 20 years. A detailed picture at the molecular level of the interaction of this autoantigen with the key elements involved in the autoimmune response, such as anti-AChR antibodies, the T-cell receptor and restricting major histocompatibility complex molecules, is now emerging for both human myasthenia gravis and its experimental model, experimental autoimmune myasthenia gravis. Here, Maria Pia Protti and colleagues focus on the molecular interactions occurring in human myasthenia gravis and summarize recent information on pathogenic mechanisms of the autoimmune response, and the structure of epitopes recognized by B cells and CD4+ T cells of myasthenic patients on the AChR molecule. PMID- 8363728 TI - Why cyclosporin is an effective drug. PMID- 8363729 TI - Nonselective actions of herbimycin A. PMID- 8363730 TI - A flaw in the detection of antigenic sites. PMID- 8363731 TI - Neural wave representation in early vision. AB - The neural wave representation which describes spatiotemporal information in early vision is proposed in terms of extended Gabor functions in this paper. Its reasonability, completeness and uncertainty in spatiotemporal domains and their frequency domains were investigated. The ranges of these parameters in this representation were estimated on electrophysiological and psychophysical data. We derived the partial differential equations which the neural wave satisfied. The general significance of 3D neural wave representation has been explored. PMID- 8363732 TI - The properties of an HBV surface antigen protein carrying the binding site for the receptor of hepatocytes--its formation of surface antigen particles and secretion from discrete cell lines. AB - A human hepatitis B virus (HBV) gene, which encodes the major surface antigen protein (S protein) carrying the hepatocyte receptor-binding site, was constructed with site-directed mutagenesis and in vitro recombination. When expressed in monkey kidney cell line COS-M6, this gene product (S309 protein) formed surface antigen (HBsAg) particles and secreted from the cells. It was stable within the cells and in the culture medium and could be immunoprecipitated with antisera directed against plasma-derived HBsAg or synthetic preS1 polypeptide. Isopycnic CsCl gradient centrifugation showed that the density of S309 protein particles (1.25 g/ml) was slightly higher than that of S protein particles. The S309 protein was readily secretable from hepatoma cell lines, and the amount secreted was comparable to that of the S protein. By contrast, only about 10% of the S309 protein was secreted from COS-M6 cells, and its appearance in culture medium was delayed. The efficiency of the secretion of the S309 protein can be improved when it is coexpressed with the S protein. PMID- 8363734 TI - Effect of the esters of gallic acid on model and human blood platelet membranes studied by Fourier transform infrared spectroscopy. AB - Gallic acid is one of the components of Chinese herbal drug Radix paeoniae used for promoting blood circulation to remove blood stasis. This paper studied the effects of gallic acid and its esters (e.g. ethyl, propyl, isobutyl and butyl gallate) on model and human blood platelet membranes by FTIR which was used for monitoring the physical state of the acyl chain, interfacial and head group region of the membrane lipid bilayer. From the experimental results it can be seen that the gallic acid and its esters have the modifying function on the pure and cholesterol-containing DPPC model membranes, and have the quantity-effective and structural-effective relationships. In addition, it is discovered that these esters have the modifying effect on the structure of human blood platelet membrane and can reverse the effect of ADP. That the effect of the esters of gallic acid counteracts the effect of cholesterol and ADP on human blood platelet perhaps provides a new explanation of the mechanism of Chinese herbal drugs used for promoting blood circulation to remove blood stasis. PMID- 8363733 TI - The production of monoclonal antibody to androstenedione and the effect of passive immunization on Xinjiang fine-wool sheep with it. AB - Five hybridomas stably secreting monoclonal antibodies (McAbs) to androstenedione were prepared by using artificially synthesized androstenedion-11 alpha-succinyl conjugate with bovine serum albumin (BSA) as antigen. These McAbs showed slightly high cross-reactivity with testosterone (8.1-12.3%) and estrone (0.8-2.5%) and high affinities ranging from 2.0 x 10(7) to 2.8 x 10(8) L/M. They were all of the IgG1 subclass. Xinjiang finewool ewes which were passively immunized with McAbs had higher circulating levels of progesterone (P) and luteinizing hormone (LH) than those of control ewes in two oestrous cycles and these changes led to increased ovulation rate and twin lambs born in young ewes. PMID- 8363735 TI - Effects of bovine follicular fluid and partially purified bovine inhibin on FSH and LH release by bovine pituitary cells in culture. AB - We have established a dispersed bovine pituitary cell culture system to study the effects of charcoal-extracted bovine follicular fluid (BFF) or bovine inhibin, partially purified by immunoaffinity chromatography (IPI), on the spontaneous release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary cells were plated at 0.25, 0.5 or 1 x 10(6) viable cells/well (c/w) and incubated for 48 h. The medium was replaced and BFF (0, 0.54, 2.7, 13.7, 68.7 or 343.5 micrograms protein) or IPI (0, 0.01, 0.06, 0.29, 1.45 or 7.25 micrograms protein) added to the cultures and the incubation was continued for 48 h. Concentrations of FSH and LH in spent medium were determined by RIA and data analyzed by ANOVA with means compared by Student-Neuman-Keuls (SNK) test. We have shown an increase in spontaneous FSH and LH release attributable to both number of bovine pituitary cells plated and to the length of incubation. The addition of BFF reduced spontaneous FSH release over 48 h incubation. The dose-dependent inhibition curves observed in culture in which different numbers of cells were plated, indicates that inhibition was greater when 1 x 10(6) c/w were plated compared to 0.25 or 0.5 x 10(6) c/w. Bovine follicular fluid at 0.45 micrograms of protein (equivalent to 0.01 microliters of BFF) incubated with 1 x 10(6) c/w, suppressed FSH release by 10.6% compare to control. Maximal suppression of 34.1% was obtained with 50 micrograms (equivalent to 1.56 microliters of BFF). Immunopurified bovine inhibin at 1.45 micrograms tended to suppress FSH release and at 7.25 micrograms significantly reduced FSH release. Neither BFF nor IPI had a measurable effect on LH release. We conclude that BFF and IPI suppress the spontaneous release of FSH from bovine pituitary cells in culture in a dose dependent manner, without concomitant suppression of LH release. PMID- 8363736 TI - Production of estradiol by the fetal rat testis. AB - Testes from 17- to 20-d-old rat fetuses were cultured in vitro for various time intervals in Medium 199 alone or with added gonadotrophins. Estradiol released into the culture media was determined by radioimmunoassay. A basal estradiol secretion rate was inexistant or undetectable at all stages studied. In early stages (17 and 18 d) there was no difference in the stimulatory effect of FSH or LH at the same concentration. At 19 d, the prevalence of FSH became apparent. At 20 d, a significant action of FSH was noted after only 3 h culture time. 1-Methyl 1, 4-androstadiene-3,17-dione, an aromatase inhibitor, markedly depressed FSH stimulated estradiol secretion. In the 20-d old testis, stimulation of estradiol production by FSH was more rapid and reached a higher level than by (Bu)2cAMP. It is suggested that the difference in the action of LH and FSH reflects the difference in the time of appearance of the corresponding receptors in the developing fetal testis. PMID- 8363737 TI - Alterations in the morphology of nuages in spermatogonia of the fish, Oryzias latipes, treated with puromycin or actinomycin D. AB - A germ-cell specific organelle, nuage, in Oryzias latipes is polymorphic. Nuages with a strand-like structure and amorphous fibrous bodies can be discriminated from each other; furthermore 2 types of nuages of intermediate morphology are also present. After the administration of puromycin or actinomycin D, nuage morphology in spermatogonia was examined by electron microscopy. Puromycin as well as actinomycin D caused a significant increase in the incidence of nuages with a strand-like structure. These observations indicate that the loss of supply of some materials can induce morphological changes in nuages, suggesting that the polymorphism in nuages of O latipes possibly results from the turnover of nuage materials. PMID- 8363738 TI - Plasma levels of luteinizing hormone in intact and castrated photosensitive blackheaded buntings (Emberiza melanocephala) exposed to stimulatory and nonstimulatory photoperiods. AB - Experiments were performed to investigate the effects of castration and/or photostimulation on plasma luteinizing hormone (LH) in photosensitive blackhead buntings. Castration evoked a significant rise in plasma LH in birds held under 8 h light: 16 h darkness (8L:16D). On exposure to 18L:6D for 24 d, both the intact birds and the castrates exhibited a significant rise in plasma LH, although the change in LH levels in the castrates was approximately 8 times greater than in the intact birds. When control birds under 8L:16D which showed no change in plasma LH up to d 13 were transferred to a 36-h resonance cycle (8L:28D), plasma LH rose significantly within 4 cycles of the treatment. Furthermore, the intact buntings showed rapid increase and decrease in the plasma LH levels during a 16 wk exposure to long (16L:8D) but not to short (8L:16D) photoperiods. These results suggest that: i) the photoperiodic drive on LH secretion is inhibited by the testes; ii) the blackheaded bunting has a strong photoresponsive system; and iii) a circadian rhythm of photosensitivity is involved in the photoperiodic time measurement in this species. PMID- 8363739 TI - Comparative duodenal, jejunal and ileal responses to luminal saline load. AB - Intestinal ionic exchanges were studied in rat duodenal, jejunal and ileal ligated loops in response to different luminal saline loads: NaCl concentration varied from 150-0 mM, solutions being made isoosmotic with mannitol. The contact delay was 60 min. An exponential relationship was found between water, Na and Cl movements and the initial saline concentration. Maximal absorption was obtained with 150 mM NaCl, and was significantly higher in the duodenum than in the jejunum and ileum. The NaCl concentration for which water, Na, and Cl movements were null was approximately 70 mM NaCl in the duodenum and jejunum, 41 mM for Na and 18 mM for Cl in the ileum. The water efflux induced by the 0-mM NaCl test solution was maximal in the duodenum (1.5 +/- 0.2 ml/h) and decreased in the jejunum (0.8 +/- 0.1 ml/h) and ileum (0.3 +/- 0.1 ml/h) as did sodium, chloride and non-chloride anion efflux. These data support the functional heterogeneity of the small intestine regulating the water and ion exchange in response to luminal saline load, the main difference being connected with the efflux capacity of the mucosa, decreasing from the duodenum to the jejunum and ileum. PMID- 8363740 TI - Effect of coconut oil in the post-weaning starter diet on growth and carcass qualities of male lambs, weaned early and intensively fattened in winter. AB - The influence of medium-chain fatty acids (5% coconut oil) introduced in a starter diet (ALc) for 21 d after weaning was investigated in 230 Lacaune male lambs. They were weaned early, intensively fattened during winter and slaughtered at a constant live-weight (39 kg). Comparisons have been made regarding the individual growth rates and carcass qualities with an isocaloric and isonitrogenous reference diet (ALr) from lamb sub-samples. During the period of actual starter diet utilization, ALc induced a higher growth rate (+ 59%) independently of the weaning weight (Wto). The feed conversion ratio was lower with ALc (P < 0.01). The induced weight difference remained after the lambs were fed on the same finishing diet. The growth pattern for the entire fattening period was more regular with ALc, particularly when lamb weight was medium (12 kg) of light (Wto < 11 kg) at weaning. The volatile fatty acid pattern in the rumen fluid over time (sampling with a rumen vacuum pump) and throughout the transition between starter and fattening diets (Rusitec procedure) did not show a clear coconut oil effect. ALc induced a slight increase in the external fat layer at slaughter 2 months later, especially in heavy lambs. Firmness and colour of subcutaneous fatty tissue were not different, but ALc tended to result in firmer and whiter carcasses in the case of the heavier lambs at weaning. PMID- 8363741 TI - [Effects of treatments (heat and fermentation by Rhizopus oligosporus sp-T3) of sweet white lupin seeds on certain factors of its nutritional use]. AB - For improving the nutritional value and functional properties of sweet white lupin (SWL), a solid fermentation process using Rhizopus oligosporus was developed for the preparation of lupin products. A comparison of the effects of soaking + thermal treatment and fermentation was made from 3 lupin products: non treated lupin seeds (SWLnt), heated lupin seeds (steamed at 100 degrees C for 30 min) (SWLh), and fermented lupin products (SWLf) from SWLh on chemical characteristics and protein efficiency ratio (PER) in rats. The major effect of soaking and thermal treatment is a loss of protein solubility and available lysine (from 3.02 +/- 0.18 g/16 g N to 2.3 +/- 0.25). Fermentation leads to a modification, of amino acid composition and to an increase in available lysine compared to heating (2.90 +/- 0.12 g/16 g N). The nutritional quality of SWLnt is low (PER = 0.83 +/- 0.09), thermal treatment decreases it (0.58 +/- 0.18) and fermentation compensates heating effect (0.74 +/- 0.25). It is suggested that the modifications of nutritional quality depends on the availability of lysine rather than on the variations of the levels of other amino acids. PMID- 8363742 TI - [Automated micro-determination by transfer analyzer of circulating alpha-amino nitrogen]. AB - An automated method for the determination of plasma free amino groups is described. The analysis is performed on a discrete computerized analyzer after plasma deproteinization using trichloracetic acid. The method is based on the formation of a complex between terminal NH2 radicals and 2,4,6-trinitrobenzene sulfonate (TNBS). The method is accurate (coefficient of variation = 2%), linear over a range of 0.2-7 mM/l and requires small analytic volumes; it also correlates well in the bovine with results from standard liquid chromatography (r = 0.953). With this method a single operator can determine free amino group contents of 50 samples per h. PMID- 8363743 TI - New whole blood analyzers and their impact on cardiac and critical care. AB - Miniaturized whole blood biosensors, patient-focused hospitals, and rising expectations of patients and physicians are shifting laboratory diagnostics to the point of care. Expanding transplantation and intensive care are increasing the need for rapid test results. Whole blood analysis improves accuracy, eliminates centrifugation, reduces response time, and conserves blood volume. Several hand-held, and over 20 portable or transportable whole blood instruments are now available. Criteria for instrument evaluation include test menus, point of-care features, analysis time, on-site performance, and information integration. Whole blood analyzers measure several vital indicators (pO2, pCO2, pH, hematocrit, K+, Ca2+, Na+, Cl-, glucose, and lactate) simultaneously in less than 2 min with less than 200 microliters of whole blood. Other in vitro tests are available (Mg2+, osmolality, CO2 content, urea nitrogen, beta hydroxybutyrate, hemoglobin, coagulation) or under development (HCO3- phosphorus). Some can be monitored in vivo (O2 saturation, pO2, pCO2, pH, glucose) or ex vivo. The clinical impact is demonstrated by ionized calcium, now established in importance for cardiac and neurologic problems, and ionized magnesium, a promising new measurement. The hybrid laboratory (a composite of conventional clinical laboratory and patient-focused testing), performance maps, and quality paths facilitate implementation of new whole blood analyzers for optimal support of cardiac and critical care, and improved patient outcomes (prospects). PMID- 8363744 TI - Clinical aspects of glycoprotein biosynthesis. AB - Glycoproteins are widely distributed among species in soluble and membrane-bound forms, associated with many different functions. The heterogenous sugar moieties of glycoproteins are assembled in the endoplasmic reticulum and in the Golgi and are implicated in many roles that require further elucidation. Glycoprotein-bound oligosaccharides show significant changes in their structures and relative occurrences during growth, development, and differentiation. Diverse alterations of these carbohydrate chains occur in diseases such as cancer, metastasis, leukemia, inflammatory, and other diseases. Structural alterations may correlate with activities of glycosyltransferases that assemble glycans, but often the biochemical origin of these changes remains unclear. This suggests a multitude of biosynthetic control mechanisms that are functional in vivo but have not yet been unraveled by in vitro studies. The multitude of carbohydrate alterations observed in disease states may not be the primary cause but may reflect the growth and biochemical activity of the affected cell. However, knowledge of the control mechanisms in the biosynthesis of glycoprotein glycans may be helpful in understanding, diagnosing, and treating disease. PMID- 8363745 TI - [The risk factors for home accidents in children. A case-control study]. AB - INTRODUCTION: The main objective was to determine the risk factors involved in unintentional injuries in children under 10 years old occurring at home. MATERIAL AND METHODS: A Case Control study was conducted in the emergency room of three pediatrics hospitals in Mexico City. The sample size was 160 cases and 320 controls. RESULTS: Boys were more affected than girls (OR) 1.7, C.I. (95%) 1.2 2.5. The age group more affected was two-three years old (OR) 1.6, C.I.1.1-2.2. When children play outside home (roof, stairs, patio) the risk was OR 2.48, C.I. 1.63-3.76. If mother is not encharged of children care (OR) 2.9, C.I. 1.8-4.8. The age > 40 years old of the person encharged of children care (OR) 2.2, C.I. 1.4-3.5. CONCLUSIONS: The results showed us how necessary is to develop injury prevention programs especially to implement passive measures, with target populations people encharged of children care. PMID- 8363746 TI - [7 years' experience with neonatal tetanus in Yucatan]. AB - Forty-six patients with neonatal tetanus (NT) were studied to identify factors for poor prognosis which could be used to select a therapeutic regimen with intravenous diazepam or neuromuscular blockade (NB) with pancuronium. Nine patients with NT grades II and III were successfully treated with diazepam; none of them died. Of the patients with NT grades IV and V, 27 received diazepam and ten received pancuronium. The mortality rate in these groups was 55% and 100%, respectively. Factors predicting poor prognosis among patients treated with diazepam were apneas (P = 0.01), and an age on admission of seven days or less (P = 0.0002). Patients who received diazepam and died, generally presented a rapidly fatal course (mean of four days); in this group tetanus was the main cause of death (73%). Patients treated with pancuronium survived a comparably longer period (mean = 15.7 days, P = 0.05), but generally died from nosocomial infections (70%, P = 0.04). On the basis of our results we propose that NT grades IV and V with the aforementioned factors for poor prognosis be treated with NB. In hospitals with limited resources and high rates of nosocomial infection, we suggest that NT grades IV and V without such factors initially be managed with diazepam, reserving NB for therapeutic failures. Finally, NT grades I-III may be effectively treated with diazepam alone. PMID- 8363747 TI - [The therapeutic use of pulmonary surfactant in neonatal hyaline membrane disease]. AB - Preliminary report of our experience with the therapeutic use of pulmonary surfactant in newborn infants of less than 30 weeks gestation with hyaline membrane disease. The use of pulmonary surfactant was held under the "rescue" modality, with up to 36 hours of postnatal life. The blood gas changes are described and the assisted ventilation progress, as well as the general response on the clinical condition of each case. Discussion in centered in the risk of use and in the criteria for prescribing the therapeutic pulmonary surfactant. It is concluded that meeting the recommended requirements for its use, the pulmonary surfactant is a therapeutic alternative in the treatment of hyaline membrane disease in newborn infants of less than 33 weeks gestation, being different the immediate ventilatory response in terms of therapeutic control, with one or other forms of pulmonary exogenous surfactant, without differences in the final result. PMID- 8363748 TI - [Variation in the blood lipids in premature newborns during the use of the "all in-one" total nutritional mixture]. AB - This prospective study was performed for the evaluation of the lipids in serum; the metabolic and other effects related with septicaemia, stability and compatibility of the parenteral nutrition combining in one continent amino acids, carbohydrates and fats; this system is called nutritional total mixture, "all in one" or three in one. Twenty prematures neonates were included in the study. The variables analyzed were: weight, gestational age; the laboratory exams taken before the installation of the system and seven days after were: total lipids, triglycerides, phospholipids, cholesterol, sodium, potassium, chloride, glucose, urea nitrogen, creatinine, hepatic enzymes and proteins, cellular blood count and coagulations tests. We obtained the next results: the mean gestational age and weight were 34 +/- 5 weeks and 1327 +/- 172 g, have been observed rise of lipids (P < 0.001), declination of potassium levels (P < 0.001), increment of calcium levels (P < 0.001), increment of albumin (P < 0.001) and platelets (P < 0.01). It is concluded that nutritional total mixture is a sure method in management of premature newborn with good stability, compatibility, with a increment of fats in serum physiological levels, with metabolic tolerance without repercussion renal, hepatic, hematological and without infections. PMID- 8363749 TI - [Anorectoplasty with a distal tubular flap via a posterior sagittal approach]. AB - Were combined posterior sagittal approach and a posterior flap of the rectal wall. This allowed to perform the pull through operation in two patients with anorectal malformation who had a prior colostomy which just one intervention. With this combination we spare surgical procedures. PMID- 8363751 TI - [Arterial hypertension in children]. AB - It is considered hypertension in children, the persistent increase of the blood pressure values above percentile 95 for age and sex, in no less than three determinations, with adequate register techniques. Blood pressure is maintained mainly by the regulation of metabolism of sodium and water in the intravascular space, through the adequate balance of intake, filtration, reabsorption and renal throughout. It is also regulated by hormonal factors. Weight gain control in teen agers could be useful to prevent high blood pressure in adults. In children, it is generally secondary to renal, reno-vascular, endocrinological or tumoral diseases. Clinical manifestations and the recommended diagnostic procedures are analysed to detect the most frequent causes of hypertension at different ages. Most cases response with antihypertensive drugs in combination with hyposodic diet. For the hypertensive crisis, asa diuretics and powerful antihypertensive drugs may be employed. Patients with chronic renal insufficiency could also need dialytic treatments. Renovascular diseases require almost always invasive treatments. Better prognosis in children with severe high blood pressure is related with recent diagnostic procedures, surgical techniques and antihypertensive drugs improvements. PMID- 8363750 TI - [The Griscelli-Prunieras syndrome: a case report]. AB - It is presented a six-year-old girl with silvered hair syndrome, of Griscelli Prunieras variety; hereditary sickness with regressive autosomic and distinguished by partial albinism and leukocytic alterations. She presented the acute phase of the sickness distinguished by: hepatosplenomegaly, thrombocytopenia, lymphadenopathy generalized, and systematic infection; it is corroborated how a hemophagocytic syndrome; during her evolution developed pancerebellar syndrome. By laboratory were corroborated: decrease phagocytosis, degranulation 0%, decrease of globulins gamma, neutropenia, skin test of PPD and Candidin negatives, there were not find the giant inclusions in bone marrow leukocyte and peripheric blood that are feature of Chediak-Higashi syndrome. Another alteration that was the distribution of mote of melanin on the hair that in the Griscelli-Prunieras syndrome are six times bigger in the Chediak-Higashi syndrome. PMID- 8363752 TI - [Drug allergy]. AB - Adverse reaction to drugs are classified as immunological and non-immunological. It is consider that one to five percent of the general population reactions to drugs. Allergic reactions are the most intense and dangerous, but they represent only five to ten per cent of all of them. Immunological adverse reactions may be induced by the drug or by their metabolites. There are risk factors to induced allergic reactions such as doses, administration time and way of administration. The four mechanism of damage from Gell and Coombs are discussed regarding to drugs, stressing the penicillin issue. Other common drugs reactions in the diary practice are cutaneous reactions with unknown immunological mechanism as it happens in febrile mucocutaneous syndrome and the phototoxic and photoallergic reactions. Pseudoallergic or "anaphylactoid" reactions have signs and symptoms like those of anaphylaxis, but the mechanism of damage is not immunological, as with local and general anesthetics and radiopaque media. Treatment for any adverse events is to stop the administration as soon as possible. The drug of choice is 1:1000 subcutaneous adrenaline besides colloid solutions, steroids and antihistaminics. PMID- 8363753 TI - Hematologic aspects of HIV infection. PMID- 8363754 TI - A survey of synthetic HIV-1 peptides with natural and chimeric sequences for differential reactivity with Zimbabwean, Tanzanian and Swedish HIV-1-positive sera. AB - OBJECTIVE: To determine whether the known sequence differences between African and non-African HIV-1 strains are reflected in the serological response. DESIGN AND METHODS: We investigated the antibody reactivity of 34 Swedish, 30 Tanzanian and 42 Zimbabwean HIV-1-positive sera to 67 synthetic peptides with sequences from North American and African HIV-1 isolates, mostly derived from regions of gag and env known to be antigenic. Not all sera were tested against all peptides. RESULTS: Differences in frequency of reactivity were noted with peptides covering the entire third variable domain (V3), which is a primary neutralization determinant, and the carboxyl terminus of gp120, in two regions of gp41, and the carboxyl terminus of p24. In env Tanzanian sera reacted preferentially with a V3 peptide from the strain JY1 (Zaire). Gradual substitutions in the central motif in V3 of ELI from GLGQ to GPGR, typical of many non-African strains, led to a gradual increase in reactivity of many Swedish sera, but did not affect Tanzanian and Zimbabwean sera, suggesting that the major epitopes recognized by these African sera are outside GPGR. V3 peptides from the MN and Z3 strains reacted with most sera, but missed 30% of those of Tanzanian origin. In the carboxyl terminus of gp120 both sets of African sera reacted preferentially with peptides from strains JY1 and MAL. Swedish sera reacted strongest with analogues from strains Z321 and HXB2. In gp41, Swedish sera showed a weak preference for reactivity with HXB2-derived peptides in the immunodominant region (amino acids 590-620), and further towards the carboxyl terminus (amino acids 620-665). CONCLUSION: The differences in serological reactivity were as great between Zimbabwe and Tanzania as between the two African sets and the Swedish. The geographical differences in the pattern of reactivity with HIV peptides probably depend on both host and viral variation and may be developed into a seroepidemiological tool, useful for optimization of future HIV vaccines. PMID- 8363755 TI - Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes. AB - OBJECTIVE: To determine the extent of genetic variation among internationally collected HIV-1 isolates, to analyse phylogenetic relationships and the geographic distribution of different variants. DESIGN: Phylogenetic comparison of 70 HIV-1 isolates collected in 15 countries on four continents. METHODS: To sequence the complete gag genome of HIV-1 isolates, build multiple sequence alignments and construct phylogenetic trees using distance matrix methods and maximum parsimony algorithms. RESULTS: Phylogenetic tree analysis identified seven distinct genotypes. The seven genotypes were evident by both distance matrix methods and maximum parsimony analysis, and were strongly supported by bootstrap resampling of the data. The intra-genotypic gag distances averaged 7%, whereas the inter-genotypic distances averaged 14%. The geographic distribution of variants was complex. Some genotypes have apparently migrated to several continents and many areas harbor a mixture of genotypes. Related variants may cluster in certain areas, particularly isolates from a single city collected over a short time. CONCLUSIONS: The genetic variation among HIV-1 isolates is more extensive than previously appreciated. At least seven distinct HIV-1 genotypes can be identified. Diversification, migration and establishment of local, temporal 'blooms' of particular variants may all occur concomitantly. PMID- 8363756 TI - Protection of monkeys by a split vaccine against SIVmac depends upon biological properties of the challenge virus. AB - OBJECTIVE: To investigate the role of the anti-cellular immune response in the protection of rhesus macaques against infection with the simian immunodeficiency virus SIVmac. To determine the biological differences between SIV challenge stocks grown either on human T-cell lines or on monkey peripheral blood mononuclear cells (MPBMC). DESIGN: A protective SIVmac split vaccine was administered to rhesus macaques and their anti-, B- and T-cell response monitored. Vaccinees and controls were challenged with SIVmac grown either on human or on monkey cells. The in vivo replication rate of, and the immune response to, the two viruses was compared. METHODS: Five rhesus macaques were immunized with a total of 2 mg each of purified SIVmac251/32H grown on the human C8166 T-cell line. The antibody and proliferative T-cell responses were evaluated by enzyme-linked immunosorbent assay and T-cell proliferation assay, respectively. Four protected animals and four controls were reboosted and challenged with MPBMC-grown SIVmac251 (SIVmac251/MPBMC). Cell-free virus load was determined by titration of plasma for SIV infectivity on C8166 cells and antigen with a core antigen capture assay. RESULTS: Protection from virus challenge with C8166-grown SIVmac251/32H or SIVmac251/MPBMC did not correlate with anti-cellular antibodies or proliferative T-cell reactivities. Control animals infected with SIVmac251/MPBMC showed high persistent antigenaemia and high plasma virus titres. Both were absent in controls infected with complement C8166-grown SIVmac251/32H. Whereas the latter always seroconverted against the full panel of viral polypeptides, SIVmac251/MPBMC-infected animals showed a drastically decreased antibody response. CONCLUSIONS: Neither the antibody nor the proliferative T-cell response to SIVmac correlates with protection from virus challenge. In contrast to SIVmac251/32H grown on C8166 cells, the MPBMC-grown challenge virus SIVmac251 appears to belong to the 'rapid-high' phenotype, possibly explaining the lack of protection against this SIV. PMID- 8363758 TI - Recombinant alpha-interferon 2b in the treatment of HIV-related thrombocytopenia. AB - OBJECTIVE: To assess the efficacy and the mechanism of action of alpha-interferon (alpha-IFN) in the treatment of HIV-related thrombocytopenia. METHODS: Thirteen HIV-positive subjects [nine men and four women with severe thrombocytopenia (platelets, < or = 30 x 10(9)/l)] were treated with alpha-IFN 2b alone at a dose of 3 x 10(6) U three times a week for 5 weeks. Haematological parameters, platelet kinetic and bone-marrow myeloid progenitor cultures [megakaryocyte colony-forming units (CFU-MK); granulocyte macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E)] were evaluated before and after treatment in responsive subjects. RESULTS: Seven out of 13 subjects showed a partial response (platelets, 50-149 x 10(9)/l) after alpha-IFN 2b therapy. Platelet survival as evaluated by 111In-oxine significantly increased, while platelet turnover showed a slight but not statistically significant increase after treatment. The growth of bone-marrow myeloid progenitor cells decreased after alpha-IFN 2b therapy, again without statistical significance. CONCLUSION: alpha-IFN 2b may increase the platelet count in HIV-positive subjects with severe symptomatic thrombocytopenia by prolonging platelet survival. The immunomodulatory and antiviral action of this drug may be responsible for prolonged platelet survival. PMID- 8363757 TI - Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent. AB - OBJECTIVE: To evaluate the potential of TraT to restore HIV-specific cell mediated immunity. DESIGN: CD4+ T cell-associated antiviral and recall antigen specific lymphoproliferative responses are generally impaired or absent in HIV infected individuals. METHODS: Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and symptomatic HIV-infected individuals, we compared the immunomodulatory effects of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. RESULTS: Exogenous IL-2 enhanced lymphoproliferation induced by an immunodominant synthetic HIV gp41 analogue, gp41[8] (amino acids 593-604), in four out of 10 asymptomatics and six out of 19 symptomatics. In contrast, TraT acted synergistically with gp41[8] to augment HIV-specific proliferation with higher frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV infected individuals, irrespective of CD4+ T-cell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other less immunodominant HIV analogues. CONCLUSIONS: These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected individuals, as well as cellular immune functions in individuals suffering from other immunodeficiency disorders. PMID- 8363759 TI - Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS. AB - OBJECTIVE: To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented. SETTING: Hospital-based HIV units. PATIENTS: Twenty-three HIV-1-seropositive patients. RESULTS: Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically. CONCLUSION: AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis. PMID- 8363760 TI - Protein-losing enteropathy and hypoalbuminemia in AIDS. AB - OBJECTIVE: To assess the contribution of protein-losing enteropathy to AIDS associated hypoalbuminemia. DESIGN: Prospective assessment of patients with AIDS. SETTING: An urban county hospital (Los Angeles & University of Southern California Medical Center. USA). PATIENTS: Four groups of patients with AIDS were studied: (1) patients with normal serum albumin (> or = 3.9 g/dl) and normal bowel habits; (2) patients with normal serum albumin and diarrhea (> or = four loose or watery stools per day for > or = 2 weeks); (3) patients with hypoalbuminemia (< or = 3.0 g/dl) and normal bowel habits; and (4) patients with hypoalbuminemia and diarrhea. MAIN OUTCOME MEASURE: Fecal alpha 1-antitrypsin concentration was used as a measure of protein loss in the gut. RESULTS: Patients with hypoalbuminemia had a significantly higher mean fecal alpha 1-antitrypsin concentration than those with normal albumin (10.8 +/- 3.0 mg/g dry stool versus 2.4 +/- 0.4 mg/g dry stool; P < or = 0.001). Although mean fecal alpha 1 antitrypsin concentrations were similar in patients with and without diarrhea in the normal albumin group, patients with hypoalbuminemia and diarrhea had significantly higher levels of fecal alpha 1-antitrypsin than those with hypoalbuminemia and normal bowel habits (17.3 +/- 5.8 mg/g dry stool versus 4.6 +/- 1.0 mg/g dry stool; P = 0.009). Twelve out of 36 (33%) patients with normal albumin had elevation of fecal alpha 1-antitrypsin compared with 33 (70%) of 47 patients with hypoalbuminemia (P < or = 0.001). Linear regression analysis showed a significant negative correlation between serum albumin and fecal alpha 1 antitrypsin concentration (r = -0.38; P < or = 0.001). Fecal alpha 1-antitrypsin was significantly higher in patients with mucosal disease visualized at upper endoscopy or flexible sigmoidoscopy than in those without gross abnormalities (13.5 +/- 5.8 mg/g dry stool versus 2.4 +/- 0.7 mg/g dry stool; P = 0.005). CONCLUSION: Protein-losing enteropathy is common in patients with AIDS and may contribute to the development of hypoalbuminemia in these patients. PMID- 8363762 TI - Risk behaviour, anti-HIV and anti-hepatitis B core prevalence in clinic and non clinic samples of gay men in England, 1991-1992. AB - OBJECTIVE: To describe the sexual risk behaviour of and HIV and hepatitis B antibody prevalence in gay men in England. DESIGN: Cross-sectional. RESPONDENTS: Gay men recruited from community settings (bars, clubs, gay organizations) and genito-urinary clinics in London, Manchester, the Midlands and Bristol; men who participated in an earlier study. METHODS: Interview including demographic information, sexual behaviour, partner type and health service use. Subjects donated saliva, which was screened for antibodies to HIV-1 by immunoglobulin G (IgG) antibody capture enzyme-linked immunosorbent assay (GACELISA) and to hepatitis B core (HBc) antigen by IgG antibody capture radioimmunoassay (GACRIA). RESULTS: Ninety-four out of 580 (16.2%) men were HIV-antibody-positive; 6.2% of men aged < or = 25 years were positive versus 19.5% of men aged > or = 26 years. HIV-antibody prevalence was highest in London (21.1%), and twice that previously reported outside London (10.5%). Ninety-four out of 568 (16.5%) men were HBc antibody-positive; 6.9% of men aged < or = 25 years were positive versus 19.7% of men aged > or = 26 years. Anti-HBc prevalence was highest in London (19.8 versus 12.7% outside London). Manual workers were more likely to be anti-HBc-positive, as were men who reported recent high-risk intercourse. Sexually transmitted diseases associated with frequent partner change (gonorrhoea, non-specific urethritis) were reported. CONCLUSION: The HIV epidemic in gay men in England continues, particularly outside London, where prevalence was double that of previous studies. We found relatively high rates of infection in young men whose main sexual experience has been in a time of unprecedented awareness of AIDS. Our data on hepatitis B suggests that further pro-active immunization programmes are urgently required. These findings add to concerns about provision of interventions targeting gay men. PMID- 8363761 TI - Sentinel surveillance for HIV-1 among pregnant women in a developing country: 3 years' experience and comparison with a population serosurvey. AB - OBJECTIVES: To establish unlinked, anonymous sentinel surveillance for HIV-1 among pregnant women attending an antenatal clinic, to determine age-specific seroprevalences, to monitor trends and to compare seroprevalence with that detected by a population serosurvey. To establish the sustainability and costs of surveillance. DESIGN: Sentinel surveillance for HIV through serial collection of unlinked, anonymous seroprevalence data from antenatal care; comparison of sentinel data with those from a population serosurvey; financial and general audit of the sentinel surveillance. SETTING: A community antenatal clinic in a large urban centre, Mwanza Municipality, Tanzania, eastern Africa, between October 1988 and September 1991. PATIENTS: Pregnant women attending for antenatal care. MAIN OUTCOME MEASURE: Age-specific HIV-1 seroprevalences, trends over time, difference from age-specific population seroprevalences, sustainability and costs. RESULTS: Overall HIV-1 seroprevalence was 11.5% (95% confidence interval, 10.5-12.4); differences in age-specific prevalences were not significant. There was no clear evidence of change in seroprevalence over the study period in any age group, although there was some indication of a rise in some age groups in 1988-1989. Sentinel surveillance among pregnant women may have significantly underestimated population HIV-1 seroprevalence for women under the age of 35 years. HIV-1 surveillance proved feasible and sustainable. Additional recurrent costs were US$1.7 per specimen for unlinked anonymous testing and US$0.57 per woman for syphilis screening. CONCLUSIONS: HIV-1 seroprevalence did not change significantly over 3 years, probably implying a substantial incidence of HIV-1 infection. In this setting seroprevalence in pregnant women may have underestimated population seroprevalence in women aged under 35 years. With modest inputs and good organization unlinked anonymous HIV-1 sentinel surveillance of pregnant women can be introduced and sustained in an African setting. This may usefully be carried out in conjunction with syphilis screening. PMID- 8363763 TI - Sex role separation in sexual diaries of homosexual men. AB - OBJECTIVE: To measure types of sex role prevalence in common and risk-related behaviours among gay men for modelling HIV transmission. DESIGN: Cohort study of 385 homosexually active men recording sexual diaries over 1-month periods. METHODS: Measures of incidence of behavioural sex roles for masturbation, fellatio, anal intercourse and anilingus by relationship type, derived from 1 month sexual diary data. RESULTS: Low behavioural role rigidity for masturbation and fellatio, but higher rigidity for anal intercourse and anilingus. Participants with no regular partner showed a relatively low frequency of anal intercourse, whereas those in closed relationships showed a high frequency. CONCLUSION: Although anal intercourse shows a certain degree of behavioural role rigidity, this rigidity is not large enough to conclude that gay men exclusively engage in either an active or a passive role. Typical rates for exclusive active and passive roles for anal intercourse during the month the diaries were recorded were in the range of 12-15%; the dual role was significantly higher. PMID- 8363765 TI - Lack of anti-nuclear antibodies during HIV infection. PMID- 8363766 TI - Secondary diabetes induced by megestrol acetate therapy in a patient with AIDS associated cachexia. PMID- 8363764 TI - Condom use with primary partners among injecting drug users in Bangkok, Thailand and New York City, United States. AB - OBJECTIVE: To determine factors associated with likelihood or failure to use condoms with primary sexual partners among injecting drug users (IDU) in two cities. DESIGN AND METHODS: Interviews were conducted with 601 IDU in Bangkok in 1989 and with 957 IDU in New York City in 1990-1991. Subjects were recruited from drug-use treatment programs and a research storefront. Informed consent was obtained and a World Health Organization standardized questionnaire about AIDS risk behaviors administered by a trained interviewer. RESULTS: A substantial minority (37%) of IDU in Bangkok and a majority (55%) of IDU in New York City reported penetrative intercourse (vaginal, anal or oral) with a primary partner in the 6 months before the interview. Of those reporting penetrative intercourse with a primary partner, only 12% in Bangkok and 20% in New York reported that they always used condoms. Parallel bivariate and multiple logistic regression analyses were conducted to distinguish between subjects who reported always using condoms and subjects who reported unsafe sexual activity with primary partners. The same two factor--knowing that one is HIV-seropositive and talking about AIDS with sexual partners--were most strongly associated with always using condoms with primary partners in both cities. CONCLUSIONS: Programs to prevent sexual transmission of HIV among IDU should provide voluntary and confidential/anonymous HIV counseling and testing, and should facilitate discussions of AIDS and sexual transmission of HIV between IDU and their sexual partners. That the same two factors were associated with always using condoms with primary partners among IDU in these two cities suggests that these factors may also be important in other groups at high risk for HIV. PMID- 8363767 TI - Kussmaul respiration and abdominal pain secondary to metabolic acidosis in AIDS patients with disseminated Mycobacterium avium complex infection receiving clofazimine. PMID- 8363768 TI - Low prevalence of positive tuberculin tests in homo-/bisexual white men from Seattle: implications for anergy testing. PMID- 8363769 TI - Fetal organs infected by HIV-1. PMID- 8363770 TI - Conversion of HIV-1 viral markers during the first few months of life in HIV infected children born to seropositive mothers. PMID- 8363771 TI - Secondary prevention of HIV: knowledge and beliefs about HIV, therapy and community resources. PMID- 8363772 TI - Helicobacter pylori infection in an HIV-seropositive patient with diarrhoea. PMID- 8363774 TI - AIDS 1992/1993. A year in review. PMID- 8363773 TI - AIDS 92/93. Virology: overview. PMID- 8363775 TI - Epidemiology of tuberculosis in the era of HIV. PMID- 8363776 TI - AIDS 92/93. Vaccines and immunology: overview. PMID- 8363777 TI - Cell-mediated immunity in HIV infection. PMID- 8363778 TI - Use of new vectors for the development of vaccines. PMID- 8363779 TI - Human trials of experimental AIDS vaccines. PMID- 8363780 TI - Primate models for HIV vaccines. PMID- 8363781 TI - AIDS 92/93. Clinical treatment: overview. PMID- 8363782 TI - Antiretroviral and immune-based therapies: update. PMID- 8363783 TI - Update on opportunistic infections. PMID- 8363784 TI - The role of lymphoid organs in the immunopathogenesis of HIV infection. PMID- 8363785 TI - Treatment and prevention of tuberculosis in HIV infection. PMID- 8363786 TI - Update on HIV and neoplastic disease. PMID- 8363787 TI - Organ-specific manifestations of HIV infection. I. Gastrointestinal diseases. PMID- 8363788 TI - Organ-specific manifestations of HIV infection. II. Update on cutaneous manifestations of HIV infection. PMID- 8363789 TI - Organ-specific manifestations of HIV infection. III. The neurology of HIV infection: clinical, pathogenetic and treatment perspectives. PMID- 8363790 TI - Organ-specific manifestations of HIV infection. IV. Oral manifestations of HIV infection: comments on the present classification. PMID- 8363791 TI - The maturation of an epidemic: update on pediatric HIV infection. PMID- 8363792 TI - Treatment, prophylaxis and research priorities for developing countries. PMID- 8363793 TI - AIDS 92/93. Social, cultural and political aspects: overview. PMID- 8363794 TI - The history of AIDS. PMID- 8363795 TI - Methodological issues in HIV/AIDS social research: recent debates, recent developments. PMID- 8363796 TI - Sustaining safe sex: sexual practices, HIV and social context. PMID- 8363797 TI - Community development as a response to HIV among drug injectors. PMID- 8363798 TI - Housing rights and housing needs in the context of AIDS. PMID- 8363799 TI - International AIDS aid: the response of development aid agencies to the HIV/AIDS pandemic. PMID- 8363800 TI - AIDS pathogenesis: mathematical models of HIV and SIV infections. PMID- 8363801 TI - HIV-1 infection of animals: the search for a pathogenesis model continues. PMID- 8363802 TI - Receptor-mediated activation of the viral envelope and viral entry. PMID- 8363803 TI - Molecular biology of HIV-1: positive and negative regulatory elements important for virus expression. PMID- 8363804 TI - AIDS 92/93. Epidemiology: overview. PMID- 8363805 TI - AIDS surveillance and prediction of the HIV and AIDS epidemic: methodological developments. PMID- 8363806 TI - Surveillance definitions for AIDS. PMID- 8363807 TI - The epidemiology of HIV-1 infection and AIDS in women. PMID- 8363808 TI - Risk factors for vertical transmission of HIV-1 and early markers of HIV-1 infection in children. PMID- 8363809 TI - HIV transmission through blood, tissues, and organs. PMID- 8363810 TI - Insurance for sickness (health insurance?) PMID- 8363811 TI - Heterotopic ossification. The utility of osteocalcin in diagnosis and management. AB - The status of 12 patients after severe traumatic brain injury was investigated to determine the clinical significance of serum osteocalcin levels during the active phase of neurogenic heterotopic ossification. The diagnosis of heterotopic ossification was confirmed on the basis of radiologic findings. The mean interval between the initial injury and diagnosis of heterotopic ossification was 29 weeks. At the time of diagnosis, serum osteocalcin and total alkaline phosphatase levels were determined along with 24-hour urinary calcium and hydroxyproline excretion. The mean serum osteocalcin level was normal at 4.3 ng/ml (normal range 1.6-6.6 ng/ml) in contrast to the elevated mean values for serum alkaline phosphatase (mean = 173 units/liter; normal range 0-105 units/liter) and urinary hydroxyproline concentration (mean = 39.6 mg/24 h; normal range 7-25 mg/24 hr). Only 17% of the subjects demonstrated an elevated serum osteocalcin level, whereas 58% of the patients had an elevated serum alkaline phosphatase level. Urinary calcium excretion and hydroxyproline excretion were elevated in 33% and 70% of subjects, respectively. These data did not reveal a significant correlation between serum osteocalcin and serum alkaline phosphatase, urinary calcium excretion or urinary hydroxyproline at the time of diagnosis or in serial measurements. Therefore, serum osteocalcin is not a valuable adjunct in confirming the diagnosis of neurogenic heterotopic ossification once the diagnosis has been suggested on the basis of clinical findings and it does not appear to play a role in assessing the maturation of heterotopic ossification. PMID- 8363812 TI - Changes in bone mineral content and density after stroke. AB - The purpose of this study was to determine whether there are differences in bone mineral content and density between paralyzed and nonparalyzed sides of patients who had sustained strokes associated with unilateral muscle weakness, to determine the relationship between duration of stroke and degree of demineralization and to compare the degree of demineralization in upper and lower limbs. The bone mineral content and density were measured by dual photon absorptiometry (high resolution scanning mode, Lunar DP4) in ambulant patients with a history of single completed strokes associated with unilateral weakness. The bone mineral content and density of each limb was determined by the region of interest analysis program. In the 30 patients included in this study, the bone mineral content and density were significantly less on the paralyzed than on the nonparalyzed side. The degree of demineralization was more pronounced in the upper than in the lower limbs. The mean percentage differences in bone mineral content and density between paralyzed and nonparalyzed arms were 13.8% (P < 0.00001) and 7.95% (P = 0.0003), respectively, and between paralyzed and nonparalyzed legs the differences were 4.5% (P = 0.0012) and 3.42% (P = 0.0028), respectively. A better correlation was noted between the time elapsed since the stroke and the degree of demineralization in the upper limbs (r = 0.75, P < 0.0001), than in the lower limbs (r = 0.60, P = 0.0004). In conclusion, patients who have strokes associated with muscle weakness are at an increased risk of developing osteoporosis on the paralyzed side and particularly in the upper limbs. PMID- 8363813 TI - Alcohol use among spinal cord-injured patients. AB - Patients with spinal cord injury (SCI) are at greater risk than others for alcohol abuse because they face physical, psychological and vocational difficulties that include sensory impairment, pain, depression and reduced opportunities to participate actively in society. This study assesses the utility of using a brief screening interview questionnaire, the CAGE (cut, annoyed, guilty and eye opener), to further evaluate patients with SCI for alcohol use, including alcoholism using retrospective data. The study explores patterns of alcohol consumption among SCI patients and investigates the relationship between self-reported alcohol use, age, previous history of drug and alcohol abuse and medical complications after discharge. Results suggest that the CAGE is a valid measure to be used with SCI patients. Age did not correlate significantly with patient's CAGE scores. However, SCI subjects with higher mean CAGE scores also had a higher incidence of medical complications. CAGE scores were significantly correlated with previous history of alcohol and drug abuse and with the average weekly number of drinks reportedly consumed before injury. PMID- 8363815 TI - Non-weightbearing exercise may increase lumbar spine bone mineral density in healthy postmenopausal women. AB - Seven postmenopausal women exercised regularly at moderate intensities (60-80% of maximum heart rate) for eight months on bicycle ergometers. Evaluation of bone mineral density by dual photon absorptiometry revealed a significant (P < 0.01) + 3.55 +/- 1.43% (mean +/- SE) increase in lumbar spine density in the exercisers compared with the 2.44 +/- 0.81% decrease noted in seven sedentary controls. No significant difference in change in femoral neck density was noted between the two groups (+2.51 +/- 2.10% v -0.74 +/- 0.72% for exercisers and controls, respectively; P > 0.10). Dietary intake of calcium and vitamin D was similar in both groups, as was previous exposure to estrogen replacement therapy. These data provide evidence of a prospective nature that non-weightbearing exercise may be effective in reversing bone loss in healthy postmenopausal women. PMID- 8363814 TI - Sympathetic skin response and R-R interval variation in rheumatoid arthritis. Two simple tests for the assessment of autonomic function. AB - Autonomic nervous system involvement with peripheral neuropathy is a well known complication of rheumatoid arthritis (RA). In the assessment of autonomic function of patients with rheumatoid arthritis, we performed sympathetic skin response (SSR) and R-R interval variation (RRIV) tests in 30 patients and in 30 normal controls. Of 30 patients, 5 had complaints of clinical dysautonomic symptoms. SSRs were abnormal in 6 of 30 patients, whereas 8 showed abnormal RRIVs during deep breathing. Nine of 30 patients also showed electrophysiologic evidence of peripheral neuropathy. All 5 of the patients with clinical dysautonomic symptoms showed abnormal SSR and RRIV test results. No patients with normal results on both tests had clinical dysautonomia. This study showed that there are frequent abnormalities in SSR and RRIV tests in patients with rheumatoid arthritis whether there is a clinical symptom of autonomic dysfunction or not. PMID- 8363816 TI - The functional significance of the fifth metacarpus and hypothenar in two useful grips of the hand. AB - Two useful grips for daily living and professional life concerning the two ulnar fingers, designated the "locking grip" and the "supporting grip," are presented. Flexion of the fifth metacarpus was recorded by an electrogoniographic method together with an electromyogram of the hypothenar muscles during formation of the two grips. For the locking grip the flexed position of the fifth metacarpus was shown to be the functional basis of the hypothenar muscles, especially the abductor digiti minimi, operating on the proximal phalanges of the little finger, thus giving full strength to the grip together with the ulnar hand flexor. For the supporting grip the flexed metacarpus enables the stretched little finger to prop up an ordinary plate and hold it horizontally. After immobilization of the ulnar fingers as a result of trauma or in the after care of cases of entrapments of the ulnar nerve, there often arise difficulties in restoring the two grips, mostly because of the atrophy of the hypothenar. A simple method, based on the statements above, of reactivating an atrophic hypothenar and exercising the fingers is suggested. A functional positioning of the fifth metacarpus and ulnar fingers during immobilization to favor the rehabilitation of the two grips is also recommended. PMID- 8363817 TI - Analysis of casualties referred to Army physical medicine services during the Persian Gulf conflict. AB - This study describes the casualties referred during the Persian Gulf War and underscores the valuable role of Army physical medicine and rehabilitation (PMR) services in evaluation and early rehabilitation of wartime casualties. Data regarding demographics, injury types, medical complications, complications of immobility and functional limitations were collected by military physiatrists at five Army Medical Centers with PMR services. Active duty soldiers injured in the Persian Gulf War who were referred totalled 222. Musculoskeletal injuries occurred in 57%, peripheral nerve injuries in 44%, penetrating wounds in 32%, fractures in 28%, brain injuries in 8%, amputations in 7%, burns in 6% and spinal cord injuries in 3%. The primary referral service was orthopedics (64%). Electrodiagnosis evaluations were performed for 41% of all referrals. Lower limb and upper limb contractures occurred in 10% and 9% of patients, respectively. Ambulatory impairments were seen in 48%. Nerve injuries were associated with penetrating wounds in 68%, with amputations in 67% and with fractures in 58%. PMID- 8363818 TI - Prevalence of kyphosis in a healthy sample of pre- and postmenopausal women. AB - Kyphosis, initially modest, progresses to the well recognized dowager's hump of the postmenopausal osteoporotic woman. Kyphosis is not only associated with relatively altered vertebral body shape (anterior wedging), but also with reduced bone density and fitness, as well as decreased muscle strength, and is associated with reduced survival. We found an unexpectedly high (35%) incidence of kyphosis in a healthy sample of well women 20 to 64 years of age. The correlation between normal postural index of kyphosis (I/K) and upright postural I/K was substantial (r = 0.799). Among the postmenopausal women, normal postural I/K was inversely correlated with age. Upright postural kyphosis was not related to age, nor was normal postural I/K in the premenopausal woman. There was no direct relationship demonstrated between current calcium consumption and I/K. Similarly, neither estrogen levels nor follicle-stimulating hormone levels were related to current posture. Women with satisfactory exercise habits had significantly lower I/K. Because the capacity to stand up straight was consistently higher than the normal postural score, yet closely correlated to it, there may be a role for postural kyphosis in changing the architecture of the vertebral column. As normal posture becomes kyphotic, an individual can no longer straighten the vertebral column. The surveyor's flexicurve, which we employed for this study, provided a simple and inexpensive method for assessing postural index. This measurement can be routinely included in the comprehensive health examination. Assessment of bone health in women should be made within the context of a fixed postural kyphosis. PMID- 8363819 TI - The difficulty placing younger Medicaid beneficiaries in nursing facilities. Commentary. PMID- 8363820 TI - Ethical considerations of goal setting for patient care in rehabilitation medicine. AB - This article examines the process of setting goals for patient treatment in rehabilitation. It explores ethical considerations and moral conflict inherent to the formulation of patient goals, and it provides a framework to help resolve such conflicts. Goal setting is also considered within the larger context of justice in the use of medical resources. PMID- 8363821 TI - A method to assess the trainee profiles of medical students attracted to our physical medicine and rehabilitation residency training program. PMID- 8363823 TI - Pathological hepatic accumulation of long-chain n-alkanes ("paraffin liver") in cows (Harbitz and Folling, 1940). An overlooked discovery. Description of lesions and identification of alkanes. AB - About 50 years ago crystalline deposits of a substance representing approximately 7 per cent wet tissue weight and believed to be hentriacontane or a mixture of similar long-chain n-alkanes (30-34 carbon atoms) were detected in two discoloured and swollen cow livers. Stored purified extracts from these livers were recently reanalysed using gas chromatography and mass spectrometry. They were found to contain about equal amounts of nonacosane and hentriacontane with a small admixture of tritriacontane and other long carbon-chain alkanes. On the basis of histological findings, five additional cases of "paraffin liver" in cows have been recorded. In the discussion comparison is made with the only known case of a similar disorder in a human, visceral accumulation of the same three alkanes as in the cows, which was recently described in the literature. Concerning the origin of the deposits, importance is given to the fact that the long-chain alkanes with odd carbon numbers identified both in cattle and man predominate in the cuticular waxes of many dietary plants. The very large quantities of the abnormal substance in the cow livers indicate low toxicity, and evidently accumulation over long periods of time. PMID- 8363822 TI - Experimental Yersinia enterocolitica infection in rodents: a model for human yersiniosis. AB - Yersinia enterocolitica infection in humans causes a broad spectrum of diseases ranging from acute bowel disease to extraintestinal manifestations such as reactive arthritis, erythema nodosum and uveitis. During the last decade a fascinating part of the molecular biology of the pathogenicity of human pathogenic Yersinia species has been unraveled. Pathogenicity factors such as protein tyrosine phosphatase, protein kinase, thrombin- and collagen-binding factors have been identified and characterized on the molecular level. In contrast to many animal models for human enteropathogenic microorganisms, experimental Y. enterocolitica infection in rodents resembles yersiniosis in humans and thus offers extraordinary opportunities to study the sequential steps of the infectious process. Rabbits are suitable animals in which to study Yersinia-induced enteritis (enterotoxin-mediated) and the humoral immune response after oral infection. The role of Peyer's patches (PP) in the entry of enteropathogenic Yersinia species has been elucidated in mice and rabbits. M cells are probably the primary target cells of invading Yersiniae. Surprisingly, after penetration of the mucosal epithelial cell layer Yersinia bacilli were visualized to be exclusively extracellular in PP tissue. Obviously neutrophils within PP were unable to phagocytize the invading microorganisms. Presently, it is not clear how the microorganisms disseminate from PP into lymph nodes, spleen, liver and lung of mice where they form abscesses and granuloma-like lesions. Immunohistologically the involvement of macrophages and T cells could be demonstrated in Yersinia-induced lesions of mice. Direct evidence for the role of T cells and cytokine-activated macrophages in the host defense reaction against a primary Yersinia infection in mice could be obtained from experiments including adoptive transfer of Yersinia-specific T cells and in vivo neutralization of TNF alpha and IFN-gamma. The experimental rat model turned out to be a suitable model for studying Yersinia-induced aseptic arthritis. Lewis- and SHR rats proved to be arthritis-susceptible. Arthritogenicity of Yersinia for rats appeared to be restricted to Y. enterocolitica of serotype 08 and correlated with the virulence potential of this serotype. Surprisingly, expression of YadA, the collagen binding factor, was not necessary for arthritis induction. A close association between both susceptibility to arthritis induction and Yersinia infection could be demonstrated in various rat strains. Depletion of alpha/beta T-cell receptor (alpha beta-TCR)-positive T cells by treatment with alpha beta-TCR-specific antibody revealed that T cells were required for clearance of the pathogen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8363824 TI - Defective T-cell stimulatory pathways in patients after allogeneic bone marrow transplantation (BMT) in man. AB - Immunological reconstitution after allogeneic bone marrow transplantation in man is characterized by a decreased lymphocyte transformation response to various mitogens and antigens during a period of from months to years. One reason for the decreased proliferative capability could be an inverted CD4/CD8 ratio; however, the present investigation demonstrates that this is not the only explanation for the immunodeficiency, since the CD4 as well as the CD8 subset, when studied in isolation, have qualitative defects, as evidenced by a reduced response of both subsets to stimulation with PHA, anti-CD2 and anti-CD3 MABs. The reason for the qualitative defect is unknown but a distorted composition of the CD4+ as well as the CD8+ T-cell subsets is suggested by the present investigations. We also observed that the PHA response was almost completely reconstituted one year after BMT, while the PWM response was still severely affected. The present study suggests that T-cell subsets which differ in their capacity to respond to PHA and PWM have different kinetics of reconstitution after BMT. PMID- 8363825 TI - Improved identification of Staphylococcus aureus using a new agglutination test. Results of an international study. AB - A new reagent for the identification of Staphylococcus aureus, SLIDEX STAPH-KIT, operates on the principle of a latex and red blood cell combination agglutination: red blood cells are coated with fibrinogen for the detection of clumping factor, and latex particles are sensitized with anti-S. aureus serotype 18 monoclonal antibody for the detection of protein A and antigen 18. French strains belonging to serotype 18 are methicillin-resistant. The performance of this reagent was compared with STAPHYSLIDE and STAPHAUREX in Europe (France, Germany, Italy), in the United States and in Japan using 548 methicillin resistant S. aureus strains, 392 methicillin-sensitive S. aureus strains, and 441 non-aureus staphylococci. The specificity of the three reagents was equivalent (98.8% for SLIDEX STAPH-KIT, 99.1% for STAPHYSLIDE, 98.1% for STAPHAUREX). SLIDEX STAPH-KIT (97.3%) was more sensitive than STAPHYSLIDE (93.5%) and STAPHAUREX (89.7%) for all S. aureus strains due to a higher rate of identified methicillin resistant S. aureus strains. PMID- 8363826 TI - Cervical cancers in Greenlandic women diagnosed after negative results on cervical cytology: perspectives in a high-risk population. AB - A total of 160 indigenous Greenlandic women had incident cervical cancer diagnosed during 1976-1991, and 41 of these women (27%) had had at least one negative smear reported during the 10 years preceding the diagnosis of cancer. Thirteen patients had previously had abnormalities of the cervix. Of the remaining 28 patients, 17 had so-called interval cancer diagnosed within three years after a negative smear result. In seven of these cases, representing 4% of all incident cancers during the period, there had previously been two or more negative smears. Suboptimal sampling of negative smears was suggested in roughly one out of two interval cancers. The results suggest that rapid biological development of cervical cancer is infrequent among Greenlandic females and that efforts should be aimed at increasing the smear test's sensitivity and providing a better follow-up of women with cervical abnormalities rather than shortening the three-year rescreening interval. PMID- 8363827 TI - Analysis of heterogeneous viral populations by direct DNA sequencing. AB - The ability of direct PCR sequencing to detect and quantify sequence polymorphisms was investigated using samples containing mixed populations of HIV 1. A part of the genome encoding the polymorphic variable region 3 of the envelope was directly sequenced to yield a consensus sequence of the virus population. The results were compared with sequences obtained by analysis of multiple clones derived from the same clinical samples. The results of five patients suggested that the direct-sequencing method can be used as a rapid tool to analyze and quantify heterogeneous viral populations. Reconstitution experiments using cloned material demonstrated that it was possible to detect and quantify minor sequence variants present in as little as 10% of the total virus population. The use of the method for molecular diagnosis is discussed. PMID- 8363828 TI - PCR amplification of HIV and cellular DNA sequences in formaldehyde-fixed, immunoreactive white blood cells. AB - Full utilization of the diagnostic power of PCR amplification of specific DNA sequences has been hampered by the logistical difficulties in handling potentially infectious human DNAs and by the polymerization of nonspecific, competing DNA products in PCR assays of low-frequency DNA sequences. To overcome these difficulties, we have devised a sensitive, specific PCR strategy that readily detects 5 copies of HIV provirus in a background of 10(5) disinfected white blood cells collected from formaldehyde-fixed peripheral blood. PMID- 8363829 TI - Quantification of hepatitis B virus DNA by competitive amplification and hybridization on microplates. AB - Present methods for quantification of hepatitis B virus (HBV) particles from serum samples are not sensitive enough for some recent clinical applications. We describe a test that allows quantification of HBV DNA in a broad dynamic range from less than 40 to 10(6) molecules based on competitive PCR. The specimen DNA and a known amount of an internal standard (IS) are co-amplified in the same tube with the same primers, one of which is biotinylated. The two biotinylated products can be quantified by hybridization on microplates coated with streptavidin, because their internal sequences are nonhomologous. An adequate standard curve is obtained by amplifying HBV DNA from a plasmid clone together with an IS. The ratio of amplified HBV DNA to IS DNA enables quantification of the original amount of HBV without tedious titrations of each sample with competitor. The lower limit for quantitative analysis with radioactive probes was between 4 and 40 virus particles in a 10-microliters serum samples. PMID- 8363832 TI - A high-sensitivity electrochemiluminescence-based detection system for automated PCR product quantitation. AB - A high-sensitivity nonisotopic system has been developed for post-PCR product detection. The probe-based detection system exploits a chemiluminescent reaction that takes place on the electrode surface in an electrochemical cell. The detection system incorporates a biotin-streptavidin capture reaction onto a solid support that permits fast post-PCR product detection at the attomole level. The system precision is within 5% relative standard deviation over a linear dynamic range of greater than three orders of magnitude. In this paper, the principles and features of the electrochemiluminescent-based detection system, together with its application to PCR product quantitation, are described in detail. PMID- 8363830 TI - Limiting detection of an amplification signal for HLA-D region and VNTR genes by 32P-PCR. AB - The limiting detection signal for identification of human genetic markers, such as HLA-D and VNTR genes, was determined using DNA isolated from a series of decreasing numbers of lymphocytes carrying the target marker in the polymerase chain reaction (PCR). The PCR procedure was assembled by incorporating 32P labeled dCTP in the reaction mixture. Primers specific for detection of MHC Class II genes such as HLA-DR1, -DR2, -DRw52 and -DRw53 were utilized when cells were mismatched by one DR type, and primers for the identification of the region of variable number of tandem repeats (VNTRs) were utilized where cells had the same DR types. The 32P-incorporated amplified DNA was analyzed by polyacrylamide gel electrophoresis followed by exposure to x-ray film. The sensitivity of the test varied for different allelic markers as evaluated by amplification of DNA from each set of a mixture of lymphocytes. The target HLA-DR markers were detectable in a cell ratio of as high as 1:100,000, whereas the VNTR markers were detectable at a 1:1000 cell ratio. The approach described here offers certain advantages: 1) increased sensitivity, 2) quantitative power, 3) reduced assay time, 4) simplified procedure and 5) less expense. This method provides valuable information for studies involving forensic specimens and marrow engraftment after allogenic bone marrow transplantation (BMT) that require discrete representation of one allele relative to another in a heterozygous sample where limited quantities of target DNA are available. PMID- 8363831 TI - Use of an automated laboratory workstation for isolation of genomic DNA suitable for PCR and allele-specific hybridization. AB - In this paper we describe the isolation of genomic DNA by using anion exchange chromatography performed on a Biomek 1000 Automated Laboratory Workstation. This procedure allows the automated isolation of DNA suitable for most molecular analyses employed in diagnosis of genetic pathologies and infectious diseases. The genomic DNA isolated by using the Biomek 1000 was indeed found to be suitable for polymerase chain reaction and allele-specific hybridization. PMID- 8363833 TI - Extraction of DNA from cryopreserved clotted human blood. PMID- 8363834 TI - Dried umbilical cords as a source of DNA for genetic studies. PMID- 8363835 TI - Prenatal diagnosis for beta-thalassemia by PCR from single chorionic villus. PMID- 8363836 TI - A method for PCR sequencing of the p53 gene from a single 10-microns frozen or paraffin-embedded tissue section. PMID- 8363837 TI - A fast method for nonisotopic single-strand conformation polymorphism. PMID- 8363838 TI - Reducing artifact and increasing the yield of specific DNA target fragments during PCR-RACE or anchor PCR. PMID- 8363839 TI - Lyophilization as a method to store samples of whole blood. AB - We have investigated the feasibility of using lyophilization as a method of preserving whole blood samples for HLA class II molecular typing. Genomic DNA extracted from lyophilized blood appears similar in size to that extracted from fresh or frozen blood and is suitable for both PCR amplification and Southern blot analysis. PMID- 8363840 TI - Simultaneous mutagenesis of multiple sites: application of the ligase chain reaction using PCR products instead of oligonucleotides. AB - A method is described for preparing mutants with multiple, site-directed mutations by ordered coupling of PCR-generated fragments catalyzed by a thermostable DNA ligase. Annealing of the sense strands of the fragments to a single-stranded (antisense) template created a full-length sense strand leaving only nicks that were closed by ligation. Mutations were introduced in the PCR primers. Following 40 cycles of denaturation and annealing, tags on the flanking primers of the ligase chain reaction product were used specifically to amplify the mutated product with specific primers that could not amplify the original template. The amplified ligation product was cloned and was found to contain the desired restriction sites introduced by way of the mutagenic primers. PMID- 8363841 TI - PCR in situ: a rapid alternative to in situ hybridization for mapping short, low copy number sequences without isotopes. AB - A new technique for rapid localization of short, low copy number sequences is described, which uses a form of PCR on preparations of fixed metaphase chromosomes on microscope slides, with the temperature cycling controlled by a flatbed thermal cycler. In its present form, the method is capable of detecting very low copy number sequences, and further development is expected to achieve the target of localizing unique sequences. It has advantages over conventional fluorescent in situ hybridization, both in the speed (easily complete within a work-day) and in the potential sensitivity. PMID- 8363842 TI - Cycle sequencing using degenerate primers containing inosines. AB - A modified protocol for cycle sequencing DNA amplified by polymerase chain reaction (PCR) is described. The method involves two sequential linear PCR amplifications using a small amount of double-stranded DNA as a template and a stringent annealing temperature: 1) alpha-35S-dATP labeling of specific primers initially in degenerate primer mixture and 2) dideoxy-ribonucleotide termination of the extended and alpha-35S-dATP-labeled specific primers. The method does not require end labeling and is useful in sequencing PCR-amplified DNA sequences from highly degenerate primers when the sequences of the regions flanking those to be primed are unknown. PMID- 8363843 TI - Preferential hybridization: amplification of hybridization signals with nested probes. AB - This paper describes a protocol for the amplification of hybridization signals using single-stranded, digoxigenin-labeled probes of increasing length. Probes of different lengths were produced by a unidirectional polymerase chain reaction. Labeled probes were purified and collectively applied for the detection of immobilized nucleic acids. The method provides for a higher signal intensity than that observed with probes that cover the entire length of the target sequence. An increase of up to 4-fold in the intensity of the detection signal was observed. PMID- 8363845 TI - [A clinico-MRI study of extrapyramidal symptoms in multiple system atrophy- linear hyperintensity in the outer margin of the putamen]. AB - We did a clinico-MRI study concerning extrapyramidal symptoms and T2-weighted MRI findings of the putamen in twenty patients with multiple system atrophy (MSA) as well as twenty-five with idiopathic Parkinson's disease. Nine out of twenty MSA patients showed extrapyramidal symptoms. And we could not observe cerebellar ataxia in two of these patients because of severe rigidity and akinesia. Eight out of nine MSA patients with extrapyramidal symptoms showed linear hyperintensity in the outer margin of the putamen. This abnormal intensity was bilateral and symmetric in most patients. However, in MSA patients without extrapyramidal symptoms, only one patient showed the linear hyperintensity. We could not find such abnormal intensity in any patients with Parkinson's disease. On proton density MRI, the signal intensity in the lesion was higher than that in the gray matter, which leads the speculation that the hyperintensity is gliosis of the putamen or increased extracellular fluid space caused by severe shrinkage of the putamen. This characteristic MRI finding is useful to distinguish MSA with extrapyramidal symptoms from Parkinson's disease. PMID- 8363844 TI - [Spinocerebellar ataxia 1--clinical study of 17 patients in a large pedigree]. AB - We studied a large pedigree with dominant spinocerebellar ataxia, genetically and clinically. At now, 27 members over 5 generations have been affected. Linkage study for the disease locus to D6S89 in a total of 44 individuals showed maximum lod scores of 3.99 at theta = 0.000. This result indicates that the disease locus of this pedigree locates near D6S89 on chromosome 6p (SCA 1). We studied 17 patients clinically. Mean age at onset was 37.7 +/- 8.6, and mean duration after onset was 11.3 +/- 6.8 years. Their clinical features were characterized by progressive ataxia, pyramidal involvement with hyperreflexia or spasticity, and mild posterior column involvement. Mild gaze nystagmus at early stage became unclear with the progress of illness. The frequent signs in the advanced stage were diffuse amyotropy, twitching of face or tongue, bulbar palsy, slow saccade, external ophthalmoparesis, mydriasis, coarse postural tremor, and dementia with emotional disturbance. There are so much clinical similarities between our pedigree and other SCA 1 pedigrees in the literature. Generally, SCA 1 shows hyperreflexia, spasticity, and terminal slow saccade. On the other hand, non-SCA 1 type OPCA is characterized by progressive hyporeflexia, slow eye movement from early stage, and frequent choreoathetosis. Gaze nystagmus, external ophthalmoparesis, amyotrophy, and spasticity are common in both SCA 1 and Machado Joseph disease (MJD). However, they are more frequent in MJD than SCA 1. Moreover, extrapyramidal signs, such as dystonia, are rare is SCA 1. Based on these difference, SCA 1 could be clinically differentiated from other similar hereditary ataxias. PMID- 8363846 TI - [Clinical research of patients with epilepsy over age 50 years--a retrospective study of early onset case]. AB - One hundred-sixteen patients with epilepsy over 50 years old were investigated to explore the clinical characteristics of epilepsy in elderly persons. Eighty-four patients having seizures within the last 3 years (residual group) were compared with 32 patients having no seizures within the last 3 years (disappeared group). Regarding the epilepsy type, there were 87 partial epilepsies (64 in the residual group and 23 in the disappeared group) which were approximately 70 percent of the total patients. Generalized epilepsies were comparatively rare in the both groups. Eleven patients with progressive myoclonus epilepsy were observed in the residual group. Regarding the seizure type, generalized convulsive seizures (GCS) were more likely to disappear than partial seizures regardless of number of seizures the patient had. Thirty-eight patients (29 in the residual group and 9 in the disappeared group) had histories of psychiatric problems. Paranoid states were most commonly seen in 12 patients in the residual group and 5 patients in the disappeared group. Intellectual disturbance was seen more frequently in the residual group. PMID- 8363847 TI - [Analysis of water content in young rats brain edema by Raman spectroscopy]. AB - Cerebral edema, classified into vasogenic edema and cytotoxic edema, has long been studied and recognized to be complicated. The authors studied the cerebral edema models of young rats suffered from cryo-injury and triethyl tin chloride (TET) injury by Raman spectroscopy which can physiologically evaluate the cerebral water content (%) of very restricted area. The cryo-injury model was conducted in the following manner. A cryo-probe (-196 degrees C) was contacted to the exposed cranium for 20 seconds in an anesthetized 4-5-week-old Sprague-Dawley young rat. A coronal section of the injured brain covered with a slide glass and wrapped by Parafilm was obtained 2, 4, 6, 8, 12, 24, 48, 72 hours after the cryo injury in order to measure the water content by Raman spectroscopy employed by Tashibu and Huizinga. TET injury model was obtained by intraperitoneal administration of TET (4.5 mg/Kg). The water content was observed by the same manner as for the cryo-injury model. Subsequent to the cryo-injury, the water content of the white matter which seemed to be higher than in adult rats increased rapidly and persisted in the same condition within 72 hours. Subsequent to TET injury, the water content of the white matter increased more rapidly than that of the gray matter, however, in adult rats the water content of the gray matter showed more rapid increase than that of the white matter. Increased water content followed by TET injury was higher in adult rats than in young rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363848 TI - [Effects of interferon-gamma on cytotoxicity of murine activated macrophages against murine glioma cells]. AB - We studied the effects of mouse IFN-gamma on the cytotoxic activity of murine activated macrophages (M phi) against mouse VM-Glioma cells (H-2b). Activated M phi were obtained from peritoneal exudate cells of mice from four strains, C57BL/6 (H-2b), C3H/He(H-2k), DBA/2 (H-2d), and BALB/c (H-2d), following intraperitoneal injection of (1) LPS 200 micrograms, (2) BCG 200 micrograms, (3) C. parvum 200 micrograms, or (4) MDP 350 micrograms 7 days prior to 20-hr 51Cr release-assay. Of the various combination of mouse strains and activating agents tested, that of activated M phi of the C3H/He mouse with induction by LPS had the most tumoricidal effect against the glioma cells, which was not MHC restricted. Although LPS-activated M phi underwent marked loss of cytotoxicity following initiation of in vitro culture, this 24 hr pretreatment with IFN-gamma inhibited this reduction in tumoricidal effects in a dose-dependent fashion. On the other hand, 24 hr pretreatment of target cells with IFN-gamma did not increase their susceptibility to lysis by activated M phi. These findings suggest that IFN-gamma augments the in vitro tumoricidal activation of M phi; This effect appears to be unrelated to any influence of IFN-gamma on target sensitivity to lysis by macrophages. PMID- 8363849 TI - [An occlusion and stenosis of the venous drainage system in cerebral AVMs- angiographical investigation]. AB - We investigated angiographically occlusion or stenosis of draining veins in cases of arteriovenous malformations (AVMs). The subjects were 51 cases who were diagnosed as cerebral AVMs by angiography in our hospital between April 1973 and January 1991. Those consisted of 8 dural AVMs, 3 mixed pial-dural AVMs, and 40 pial AVMs. Angiography was stereoscopically done in all cases. Angiograms obtained prior to treatment were retrospectively analyzed. Cases of dural AVMs or arteriovenous fistulae in the cavernous sinus were excluded from the subjects. Eight of 51 cases (16%) had occlusion or stenosis of draining veins; i.e., 2 dural AVMs, 1 mixed pial-dural AVM, 5 pial AVMs. One of 2 dural AVMs was located in the sigmoid sinus, and another involved the superior sagittal sinus. One mixed pial-dural AVM was a vein of Galen aneurysm. Occlusion or stenosis was recognized at the junction of the vein of Galen to the straight sinus (3 cases), in the straight sinus (2 cases), at the junction of the vein of Labbe to the transverse sinus (1 case), in the superior sagittal sinus (1 case), and in the sigmoid sinus (1 case). Two of 8 cases with occlusion or stenosis of draining vein presented with hemorrhage at the site of AVMs. In cases of pial AVMs, occlusion or stenosis of draining vein seemed be related to endothelial changes due to turbulent and irregular flow. On the other hand, in cases of dural AVM with dural sinus occlusion, sinus abnormalities may precede the formation of fistulous communications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363850 TI - [Sequential changes in SPECT using 201T1 chloride during the treatment of intracranial gliomas]. AB - The authors followed up the change in SPECT using 201Tl chloride (Tl-SPECT) according to the course of treatment of intracranial gliomas and analyzed the difference in Tl-SPECT between the stable and progressive groups. The subjects were 26 series of supratentorial gliomas subjected to Tl-SPECT before and after the treatment (radio-therapy and chemotherapy). They were put on Tl-SPECT after 10 minutes (early image) and 4 hours (delayed) following 74 MBq of 201Tl chloride intravenous injection. Besides, RI count ratio (L/N) in the tumor lesion (L) and contralateral parenchyma (N) was measured. The patients were divided into stable and progressive groups judging from the therapeutic effects, the change in L/N ratio between before and after the treatment was analyzed. The stable group showed a significant post-treatment decrease in L/N ratio compared with a significant post-treatment increase therein for the progressive group. This result suggested Tl-SPECT to change according to the course of treatment and to be applicable to the judgement of the therapeutic effect on gliomas. PMID- 8363851 TI - [Herpetic simplex encephalitis followed by myelopathy]. AB - A 48-year-old male was admitted to our hospital because of fever, headache and vomiting. At admission, the level of consciousness was depressed (drowsy) with slight confusion. Extremely miotic pupils, nuchal stiffness, ataxia and myoclonic movements of both upper limbs were observed. The eye movements were almost normal and there was no definite limb weakness or sensory impairment. A few days after admission, his level of consciousness further decreased, and opsoclonus, ataxic breathing and intestinal paralysis appeared. The body temperature fluctuated remarkably ranging from 33.0 degrees C to 39.0 degrees C. The cerebrospinal fluid (CSF) examination revealed lymphocytic dominant pleocytosis, increase of protein and decrease of glucose. Enzyme-linked immunosorbent assay (ELISA) showed increased antibody (IgG) to herpes simplex virus (HSV) in both serum and CSF. The antibody in CSF further elevated at the later examination. Magnetic resonance imaging (MRI) demonstrated high signal intensity areas mainly in the cerebellum and sporadically in the supratentorial subcortical white matter on T2-weighted images. Administration of Gadolinium-DTPA also revealed an additional lesion in the pons. From these findings, he was diagnosed as herpetic encephalitis involving the brainstem and the cerebellum, and acyclovir was administered. Although his initial symptoms and signs started to recover three weeks after admission, he newly developed complete flaccid paraplegia, dysuria and sensory disturbance with the spinal cord level of the 4th thoracic segment. The oligoclonal IgG bands were detected in the cerebrospinal fluid of the convalescent stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363853 TI - [A case of cervical vagus neurinoma with hypoglossal palsy]. AB - Cervical vagus neurinoma with hypoglossal palsy is extremely rare and only one case has been reported so far in Japan. A 52-year-old female complained of dysarthria. She has hypoglossal palsy with left-deviated tongue and the left half of her tongue was markedly atrophic. Cervical mass was not palpable and she had no other complaint such as hoarseness or dysphagia. CT scan and MRI revealed a tumor at a caudal part of the left jugular foramen. A hypoglossal canal was intact. Cerebral angiography demonstrated arterio-venous dissociation but vascular formation or tumor stain was not revealed. The tumor was totally removed by transpetrosal approach. The vagus nerve became thicker above C2 level and changed into the yellowish tumor with clear margin. The hypoglossal nerve was compressed between the tumor and an occipital bone. The authors think this is why hypoglossal palsy appeared. Histologically, the tumor was neurinoma. Clinical symptoms, diagnosis, and treatment were discussed. PMID- 8363852 TI - [Cerebellopontine angle lipoma--case report]. AB - Intracranial lipomas are rare. Cerebellopontine angle lipomas are extremely rare. We report a case of right cerebellopontine angle lipoma. A 47-year-old woman has been suffering from right trigeminal neuralgia for about 1 year. Neurological examination showed right 5th and 8th cranial nerve dysfunction. MRI demonstrated the high intensity mass lesion at right cerebellopontine angle. The lesion was demonstrated as negative intensity in an opposed image by using Dixon's technique. CT showed the lesion as a very low density area (-104 Hounsfield units). Subtotal removal of the tumor was performed following right suboccipital craniectomy. Pathological diagnosis was lipoma. We review the literature on this rare tumor and discuss the clinical symptoms, radiological findings and management. We suggest that the operation should be prudently performed for the case with only hearing disturbance because there is a high possibility that hearing disturbance will worsen. PMID- 8363854 TI - [A 70-year-old man with right hemiparesis and mutism]. AB - We report a 70-year-old man who had a sudden onset of right hemiparesis and mutism. The lower extremity was more involved than the upper one. He had a long history of diabetes and chronic renal failure for which hemodialysis was necessary. On August 30, 1990, he had an sudden onset of right hemiparesis and mutism. Neurological examination revealed awake but mute in no acute distress. He could only respond to very simple commands such as opening his mouth or protruding his tongue. He did not appear to understand more difficult questions. In addition, he could not answer verbally. He was totally mute. Cranial nerves appeared intact except for slight right central facial paresis and severe diabetic retinopathy. He had complete paralysis of his right leg and a moderate weakness in his right upper extremity. Deep reflexes were diminished in both upper extremities and absent in the lower limbs. Frotal signs such as grasp and snout reflexes were present. Cranial CT scans revealed an ill-defined low density area in the left parasagittal subcortical area and a part of the anterior cerebral artery territory. The supplementary motor area appeared at least in part to be involved. He was treated with glycerol and other supportive cares, however, his clinical course was complicated by pneumonia, heart failure, septicemia, and he expired two months after his stroke. The patient was discussed in a neurological CPC, and the chief discussant arrived at a conclusion that he had an artery-to-artery embolism at the internal carotid bifurcation resulting in the cerebral infarction mainly in the territory of the anterior cerebral artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363855 TI - Quantitative analysis of trabecular bone structure. PMID- 8363856 TI - Marrow space star volume can reveal change of trabecular connectivity. PMID- 8363857 TI - Relation between 2- and 3-dimensional architecture of trabecular bone in the human spine. AB - By means of a new preparation technique which allows the combined 2- and 3 dimensional analysis of trabecular bone we analyzed the vertebral bodies of 22 autopsy cases. None of these cases had any skeletal disease. With increasing age bone volume was decreased in all vertebral bodies (2nd cervical to 5th lumbar body) but this decrease was more pronounced in the lower vertebrae. In the upper cervical spine there was nearly no age-related loss of trabecular bone volume. 3 D analysis demonstrated that the loss of bone tissue is due to a loss of trabecular plates which are transformed to trabecular rods by perforations. The number of plates and rods could be measured directly. In the 2nd lumbar vertebra at the age of 20 years the density of plates was 0.61 mm, the density of rods was 0.2/mm. At the age of 80 years the density of plates was 0.2/mm. The density of rods remained constant at all ages. Perforations could be seen directly. They were located mainly in trabecular plates. At higher ages they occurred in rods either. The number of vertically oriented trabeculae was about twice the number of horizontal ones. The rate of age-dependent reduction of trabeculae was the same in horizontal and vertical trabeculae. It was possible to do real 3 dimensional measurements of the diameter of trabecular rods. These values were compared to the calculated values of trabecular plates. In mean trabecular plates are thinner than rods. It could be demonstrated that microcallus formation is a common feature in the human spine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363858 TI - Stereology and histogram analysis of backscattered electron images: age changes in bone. PMID- 8363859 TI - Changes of interstitial bone thickness with age in men and women. AB - Mean interstitial bone thickness has been estimated from mean trabecular thickness and mean wall thickness (It.Th = Tb.Th-2*W.Th) with varying results. Some authors found age-related changes of It.Th while others did not. We measured It. Width (It.Wi, 2D) directly, in cancellous iliac crest bone from 23 women aged 20-78 yrs. and 21 men aged 23-74 yrs. At grid-selected sites coupled measurements were done of Tb.Wi and It.Wi, together with W.Wi. It.Wi was defined as the distance between cement lines nearest to the surface at both sides of a trabecula. A thionine stain was used to visualize the cement lines. When the persons studied were divided into two age groups: 20-49 yrs (Group 1) and 50-79 yrs (Group 2) significant but opposite age-related trends were seen both in men and women. Group 1: Men: r = -.68; p < .02; n = 11; Women: r = -.68; p < .02; n = 11. Group 2: Men: r = .79; p < .01; n = 10. Women: r = .59; p < .05; n = 12 (r = coeff. of correlation). Men: It.Wi 63.3 microns (3rd decade [dec.]); 50.8 microns (6th dec.); 67.8 microns (8th dec.). Women: It.Wi 63.7 microns (3rd dec.); 48.3 microns (6th dec.); 63.8 microns (8th dec.). Measured It.Wi values appeared considerably larger than their calculated counterparts (mean delta: 35%). The decline of It.Wi is interpreted as a sign of negative bone balance at the BMU level, leading to thinning of trabeculae, the subsequent increase has to be the result of both declining resorption depth and disappearance of the thinner trabeculae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363860 TI - The Conneulor: unbiased estimation of connectivity using physical disectors under projection. AB - The Euler number and the connectivity of an arbitrary object is defined, and it is illustrated why the connectivity of an n-dimensional object cannot be estimated in an (n-1)-dimensional section. The disector--principle for 3-D counting of the Euler--events is illustrated in cancellous bone. The correct handling for unbiased counting of events at artificial edges is outlined. A nomogram for predicting the precision of an estimate is provided. PMID- 8363861 TI - Repair of large cortical defects with block coralline hydroxyapatite. PMID- 8363862 TI - Structural and cellular assessment of bone quality of proximal femur. PMID- 8363863 TI - Histomorphometric analysis of tricalcium phosphate ceramic implanted into turkeys. AB - Porous cylinders of tricalcium phosphate of two pore size distributions and four pore densities were implanted bilaterally into the ulnae of twelve skeletally mature turkeys. Morphometric analyses at two, four, and six post-operative months indicate implant resorption begins prior to the second post-operative month and that physical changes and biologic response continue at a rate dependent upon pore size distribution. PMID- 8363864 TI - Methods for the histological study of femoral neck bone remodelling in patients with fractured neck of femur. PMID- 8363865 TI - The identification of cortical microdamage in fatigue-loaded bone using a non invasive impulse response vibration testing technique. PMID- 8363866 TI - Determination of femur structural properties by geometric and material variables as a function of body weight in rats. Evidence of a sexual dimorphism. AB - Femur diaphyses of male and female Wistar rats were densitometrically and biomechanically assayed. The BMD-dependent material properties were better in female than in male bones, but cross-section geometric properties were better in male femurs. As a result, mechanical properties of the integrated diaphyses were better in males, but differences disappeared after statistical adjustment of data to a common body weight. Results evidence a feed-back mechanism locally controlling the strain-dependent bone modelling and the corresponding cross sectional design as related to bone stiffness, with a set-point adjusted to animal biomass. A sexual dimorphism of bone biomechanics is also described for the species. PMID- 8363867 TI - Insulin like growth factors and the local regulation of bone formation. PMID- 8363868 TI - Anabolic effect of parathyroid hormone on cancellous and cortical bone histology. PMID- 8363869 TI - Prostaglandin E2 restores cancellous bone to immobilized limb and adds bone to overloaded limb in right hindlimb immobilization rats. AB - The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127% to +188%) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363870 TI - Alkaline phosphatase-positive human osteoblasts do not normally express MHC class II antigens in vivo. PMID- 8363871 TI - Estrogen induces bone formation on non-resorptive surfaces in the rat. AB - We have recently found that 17 beta-estradiol (E2) stimulates bone formation in rat cancellous bone, and that this bone formation is suppressed by (3-amino-1 hydroxypropylidene)-1-bisphosphonate (AHPrBP). To analyse the relationship between bone resorption and bone formation in the action of E2, we injected 13 week-old female rats sequentially with three fluorochromes (calcein, tetracycline and xylenol orange) at 7-day intervals. E2 (40 micrograms/kg) or vehicle was injected daily for 15 days, starting 24 hrs after the first fluorochrome. A third group was injected with AHPrBP (0.3 mg/kg) 24 hrs after the first two fluorochromes. The rats were killed 48 hrs after the third fluorochrome. We found that the perimeter of all three fluorochrome labels was increased by E2. The entire perimeter of the first label was non-crenated. Since the first label was given before E2-administration, this suggests that label that would otherwise have been eluted from the bone surface had been fixed in bone by E2-induced bone formation, which might have occurred either through prolongation of pre-existing bone formation, or induction of bone formation on quiescent surfaces. In either case, our results suggest that resorption did not precede formation at the site of bone formation. Since induction of bone formation by E2 is suppressed by inhibition of bone resorption, this suggests that the coupling of E2-induced formation to resorption in the rat does not necessarily require that formation occurs at the same site as bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363872 TI - A method for the localization of cytokine mRNA expression in adult human bone by in situ hybridization. PMID- 8363873 TI - Analysis of gene expression in skeletal tissues by in situ hybridization. PMID- 8363874 TI - Marrow stromal (Western-Bainton) cells: identification, morphometry, confocal imaging and changes in disease. PMID- 8363875 TI - Evaluation of osteoblastic activity by morphometric comparison of alkaline phosphatase cytochemistry vs. tetracycline fluorescence. AB - Alkaline phosphatase (ALP) activity was used as a novel histomorphometric index of osteoblastic surfaces involved in mineralization. The enzyme cytochemical reaction was done on sections of low temperature processed, glycol methacrylate (GMA) embedded bone biopsies from 39 patients with various types of renal osteodystrophy (age 48 +/- 12 yrs; 19 males, 20 females) who had received tetracycline labelling. Sets of three serial sections were obtained from each tissue block: the 1st section (2 microns thick) was stained with Methylene blue Azure 11 for morphology; the 2nd section (2 microns thick) was used for ALP cytochemistry; the 3rd section was left unstained for UV microscopy. ALP positive osteogenic cells on bone surfaces displayed either of two distinct morphologies: a) typical plump, 'active' osteoblasts, and b) flat, elongated cells otherwise indistinguishable from 'bonelining cells'. These ALP+ flat cells were in contact with sites of active osteoid and mineral deposition and also codistributed with tetracycline labels outside of, and in continuity with, osteoid seams. Flat lining cells which were ALP negative were never associated with labels. Therefore, ALP activity also provided an objective criterion for differentiating two different 'phenotypes' among flat bone lining cells (ALP+ and ALP-), associated or not associated with matrix mineralization, respectively. The following histomorphometric variables were measured: Ob.S/BS, OS/BS, MS/BS and ALP.S/BS. Ob.S/BS, OS/BS and MS/BS were different in different types of ROD. However, OS/BS always exceeded MS/BS which, in turn, always exceeded Ob.S/BS. ALP.S/BS exceeded OS/BS in controls, mixed ROD and hyperparathyroidism, whereas the reverse occurred in osteomalacia and aplastic bone, due to the abundance of ALP lining cells over nonmineralizing surfaces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363876 TI - Immunohistochemical study of activating osteoblasts from undifferentiated mesenchymal cells by electrical stimulation. PMID- 8363877 TI - Gene expression at single cell resolution associated with development of the bone cell phenotype: ultrastructural and in situ hybridization analysis. PMID- 8363878 TI - A comparison of microanatomic basis for coupling between bone formation and bone resorption in man and the rat. AB - The trabecular bone of the secondary spongiosa of mature rats shows a coupling of bone formation to resorption. In adult man the coupling of formation and resorption involves a site-specific sequence of events, in which bone resorption is normally followed, at the same site, by bone formation. Whether the coupled processes of bone resorption and formation also occur at the same site in the rat is unknown. To elucidate the spatial relationship between bone formation and resorption in the rat, we compared the percentage of crenated and non-crenated cement lines with the percentage of crenated and non-crenated bone surfaces in the proximal tibia of adult rats aged 16 weeks-two years. A similar comparison was also made using bone from adult human iliac crest. We found that the trabecular bones of 16-week and seven-month-old rats exhibited a low percentage of crenated cement lines. In contrast, the surfaces of rat bone trabeculae showed a similar low proportion of crenated surface to human bone. However, in older (two years) rats, in which bones have ceased to grow in length, the percentage of cement lines that were crenated increased to towards human levels. These results imply that most of the bone formed in the secondary spongiosa of growing rats occurs on non-resorbed surfaces. Thus, although there is substantial evidence that bone formation is coupled to resorption in the rat, such that increased resorption is associated with increased formation, and suppression of resorption suppresses bone formation, bone formation does not necessarily occur on a previously resorbed site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363879 TI - Characterization of osteopenia in feline mucopolysaccharidosis VI and evaluation of bone marrow transplantation therapy. AB - Studies on a feline model of MPS VI demonstrated a marked osteopenia in iliac crest bone samples from young adult animals with fewer, finer trabeculae. In the absence of significant differences in bone remodeling, this was considered due to defects in endochondral ossification and the formation of fewer trabeculae. Cell level bone formation was normal despite the presence of vacuolated osteoblasts. Affected animals had vacuolated osteocytes in larger lacunae. Cats of the same age who had received a bone marrow transplant 12 months prior as young kittens, had significantly more trabecular bone with thicker trabeculae. The presence of smaller osteocyte lacunae in these animals as compared to their untreated MPS VI cats appeared to be a direct effect of bone marrow transplantation and a useful parameter to monitor its efficacy. PMID- 8363880 TI - Animal models for the study of bone loss after cessation of ovarian function. PMID- 8363881 TI - Calcium-restricted ovariectomized Sinclair S-1 minipigs: an animal model of osteopenia and trabecular plate perforation. AB - The ovariectomized rat model has now been generally accepted as a useful model for screening different therapeutic agents, but there is a major requirement to identify reliable large animal models for osteoporosis research. In this study, the calcium restricted, ovariectomized minipig has been thoroughly investigated in order to define a large animal model with trabecular and cortical bone remodeling which would be reliable for further testing of agents that had shown promise of efficacy during the screening procedure. Twenty six female, 4-month old minipigs were randomized into four groups and fed either normal diet (0.90% calcium (Ca.)) or diet with restricted calcium content (0.75%, 0.50%). At the age of ten months, 3 groups were ovariectomized (OVX) while one group on normal diet was shamoperated. The groups were followed for six months after the operation. At death, bone mass was determined by densitometry and by ashing. Additionally, biomechanical competence was assessed in trabecular bone cores from the vertebral bodies. Finally, histomorphometry (static and dynamic parameters) and structural analyses (star volume) were performed on the vertebral bodies. The study revealed an OVX-related decline of 6% in vertebral bone mineral density (BMD) and a decline of 15% in trabecular bone volume (BV/TV). In contrast, a 15% increase in mean trabecular plate separation (Tb.Sp.) and a small increase in marrow space star volume (Ma. Star V.) were detected. The structural changes became more pronounced when OVX was combined with mild Ca. restriction (0.75% Ca.) with an increase in Ma. Star V. to 164%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363882 TI - Bone histomorphometry in baboons in captivity. PMID- 8363883 TI - The long-term effect of ovariectomy on the quality and quantity of cortical bone in the young cynomolgus monkey: a comparison of density fractionation and histomorphometric techniques. PMID- 8363884 TI - Bone remodeling during calcitonin excess: reconstruction of the remodeling sequence in medullary thyroid carcinoma. PMID- 8363885 TI - Primary hyperparathyroidism: iliac crest cortical thickness, structure and remodeling evaluated by histomorphometric methods. Aarhus Bone and Mineral Research Group. PMID- 8363886 TI - Non-invasive measurements of bone mass in adult renal osteodystrophy. PMID- 8363887 TI - Long-term effect of oral calcitriol pulse therapy on bone in hemodialysis patients. PMID- 8363888 TI - Synergistic effect of 1,25-vitamin D3 and fluoride on bone aluminum accumulation. PMID- 8363889 TI - Morphometry of bone resorption: introduction and overview. PMID- 8363890 TI - Assessment of erosion depth by lamellar counting. PMID- 8363891 TI - Assessment of resorption cavity characteristics in trabecular bone: changes in primary and secondary osteoporosis. PMID- 8363892 TI - Histomorphometry of Howship's lacunae formed in vivo and in vitro: depths and volumes measured by scanning electron and confocal microscopy. PMID- 8363893 TI - Proliferation of bone surface-derived osteoblastic cells and control of bone formation. PMID- 8363894 TI - Histomorphometry of active osteoblast surface labelled by antibodies against non collagenous bone matrix proteins. PMID- 8363895 TI - Osteoblast density and the evolution of BMUs in vertebral osteoporosis. PMID- 8363896 TI - Greater bone formation induction occurred in aged than young cancellous bone sites. AB - We have determined the differences in the effects of continual prostaglandin E2 (PGE2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE2/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE2/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE2 treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE2 treatment than young growing metaphysis. PMID- 8363897 TI - Calculation of active formation period using label escape and three labels. PMID- 8363898 TI - Maintaining restored bone with bisphosphonate in the ovariectomized rat skeleton: dynamic histomorphometry of changes in bone mass. AB - This experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an antiresorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE2/kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE2 treatment and began treatment with 1 or 5 micrograms/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the proximal tibial metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE2 treatment was stopped, the PGE2-induced cancellous bone disappeared. In contrast, 5 micrograms of Risedronate inhibited the bone loss and maintained it at the PGE2 treatment level. The key dynamic histomorphometry value for the restore (R) and maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 microgram Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5 micrograms Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE2 after discontinuing PGE2 by administering enough Risedronate, a resorption inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363899 TI - The aminobisphosphonate alendronate inhibits bone loss induced by thyroid hormone in the rat. Comparison between effects on tibiae and vertebrae. AB - The aims of this study were to develop a rat model of hyperthyroidism and to determine the efficacy of alendronate in the prevention of thyroid hormone induced bone loss. Ten week-old Sprague-Dawley rats injected with thyroxine 250 micrograms/kg/day (+T4) or vehicle (-T4) were treated with alendronate (+ALN) or vehicle (-ALN) orally 0.5 mg/kg/day. After 3 weeks of treatment histomorphometric parameters of cancellous bone remodeling were assessed in the proximal tibia and in the first lumbar vertebra. In the secondary spongiosa of the tibia T4 treatment caused significant bone loss, associated with increased bone turnover; trabecular bone volume, trabecular thickness and trabecular number were significantly decreased. Osteoid and osteoclast surfaces increased in +T4/-ALN as compared to control. Alendronate prevented the increase in bone turnover and increased bone volume above control values without interfering with the recruitment of osteoclasts. These changes were not apparent in the vertebra. It is concluded that excess thyroid hormone in the rat induces high turnover bone loss in the tibia which can be prevented by alendronate through an inhibition of osteoclastic activity. The lack of effects of thyroid hormone on the vertebra may be ascribed to a lower rate of basal bone turnover at that site. PMID- 8363900 TI - Histomorphometric effect of six month treatment with oral Risedronate in patients with multiple myeloma. PMID- 8363901 TI - Immobilisation induced bone loss in the sheep is not modulated by calcitonin treatment. AB - The effect of calcitonin on immobilisation-induced loss of cortical and trabecular bone was studied in adult female sheep. The left calcaneus of 24 adult female Welsh mountain sheep was protected from normal loading by placing an external fixator across the hock joint, from the tibia to the metatarsus. In vivo strain gauge recordings from similar animals showed that this procedure resulted in a 50% reduction in principal strain magnitude in the shaft of the calcaneus during walking. All animals received intramuscular injections three times weekly. Half of the sheep received 100 i.u. of salmon calcitonin while the remainder received vehicle alone. The experiment was conducted blind. Over the 12 week period of the experiment, dual photon absorptiometry was performed at monthly intervals to measure the bone mineral content (BMC) of the calcanei. In all the animals, the loss of bone associated with the functional protection afforded by the fixator was highly significant (p < 0.0001). There was however, no significant difference in either the amount or rate of bone loss between animals which had received calcitonin and those which had not. Post mortem measurement of the cortical thickness of the shaft of the calcaneus revealed a specific pattern of loss which was also not different in the two groups. In this model, calcitonin treatment was ineffective in preventing or retarding loss of bone associated with reduced functional load-bearing over a 12 week period. PMID- 8363902 TI - Relationship between bone formation rate and osteoblast surface on different subdivisions of the endosteal envelope in aging & osteoporosis. PMID- 8363903 TI - Early histomorphometric changes in response to parathyroid hormone therapy in osteoporosis: evidence for de novo bone formation on quiescent cancellous surfaces. PMID- 8363904 TI - In vitro tetracycline labelling and bone cell survival in human trabecular bone explants. AB - Results are presented which document the feasibility and utility of human trabecular bone explants for in vitro bone research. This approach is advantageous because it allows bone cells to maintain their natural orientation on the endosteal surface, and keeps surrounding marrow intact--thus retaining the immediate local microenvironment. In addition, bone cells are not exposed to transient, but sometimes harsh, isolation procedures. Data are presented which show greater initial bone cell numbers from younger donors and the change in these numbers over culture periods up to 21 days. A technique is presented which achieves single and double tetracycline label incorporation into the mineralizing front of bone explants in vitro using a pulse-chase methodology. PMID- 8363905 TI - Optimizing multiple fluorochrome bone histodynamic markers. PMID- 8363906 TI - Electron microscope examination of osteoblast-like cells (ROS 17/2.8) after colorimetric evaluation of the proliferation. PMID- 8363907 TI - Quality assurance-quality control in bone histopathology and bone histomorphometry. PMID- 8363908 TI - Strategies for regenerating bone of the craniofacial complex. PMID- 8363909 TI - A non-human primate model for the study of osteoporosis and oral bone loss. PMID- 8363911 TI - You make the diagnosis: case study. Ineffective airway clearance, fluid volume deficit. PMID- 8363910 TI - Alveolar bone augmentation following the local administration of prostaglandin E1 by controlled-release pellets. AB - E-Series prostaglandins (PGE) are powerful osteogenic substances when given in vivo. The purpose of this work was to determine the ability of locally administered PGE1 to promote alveolar bone formation. Controlled-release pellets containing PGE1 were implanted on the lateral mandibular surface of Beagle dogs and tissues collected 4 weeks later. There was a dose-related increase in alveolar bone thickness and bone formation rates following PGE1 administration. In many cases, there was substantial new bone formation on the alveolar crest. Some increase in alveolar bone remodeling occurred with higher doses of PGE1. These results demonstrate that locally administered PGE1 may be useful for the augmentation of alveolar bone. PMID- 8363912 TI - Nursing diagnoses and functional health patterns in patients receiving external radiation therapy: cancer of the digestive organs. AB - A descriptive study using clinical methodology was conducted to identify and describe core and site-specific symptoms reported by 15 patients with cancer of the digestive organs who received external radiation therapy. A 47-item Radiation Symptom Scale was designed by the investigators for this study. Symptoms identified by patients with a mean occurrence of at least "sometimes" were considered potential defining characteristics and were submitted to a panel of experts for identification of nursing diagnoses. Seventeen nursing diagnoses, with their associated defining characteristics, were identified and classified within eight Functional Health Patterns (FHP). Half of the nursing diagnoses were formulated within the Nutritional-Metabolic and Elimination patterns. Four of the FHPs were related to primarily functional patterns; four were primarily psychological-behavioral. Results of the study describe the nursing needs of patients who receive radiotherapy to the digestive organs. PMID- 8363913 TI - Nursing diagnosis by computers: an application of neural networks. AB - In a pilot-test application of the neural network, test case diagnoses made by the ART-2 neural network agreed with those made independently by nurses. The main conclusion is that the ART-2 neural network is promising as a decision-making aid. It can handle probabilistic and ill-defined data through a process of pattern recognition without programming rules. A disadvantage is that the ART-2 neural network requires "training" by the nurse using at least one example to define a diagnosis. In practice, however, this requirement does not affect its usefulness. Moreover, providing the ART-2 neural network with several training examples enables it to identify new patterns that are "close" to the textbook case but vary in one or more characteristics. PMID- 8363914 TI - High risk for violence. PMID- 8363916 TI - You make the diagnosis: case study. Ineffective airway clearance. PMID- 8363915 TI - Validation of social isolation related to maturational age: elderly. AB - The purpose of this study was to obtain expert validation of the defining characteristics used when diagnosing social isolation in the elderly and to compare these characteristics with those identified in the NANDA Taxonomy I Revised (1990) and the characteristics identified by the investigator through a literature review. A descriptive survey design using Fehring's Diagnostic Content Validity Model and a Q-Sort methodology was used. The sample consisted of 300 registered nurses (68% response rate) selected randomly from the ANA's Council of Gerontology and Community Health. Findings suggest the need for clinical validation of this diagnosis and the possible need for the addition of developmental age categories to the defining characteristics of social isolation. PMID- 8363917 TI - Taxonomic validation: an overview. AB - A valid taxonomy legitimizes the elements that make up the taxonomy and increases trust in its generalizability and predictability. There is a concern that the NANDA Taxonomy is not a valid taxonomic structure. Despite on-going work to validate individual nursing diagnoses, there is little research that focuses on validation of groups of diagnoses (taxons) within the NANDA taxonomy. This last article in a series of four will familiarize the readers with why, what, and how a taxonomy of nursing diagnoses can be validated. This article highlights assessment of the validity and reliability of a taxonomy, compares the process of taxonomic validation to the research process, and explores examples of validation design. PMID- 8363918 TI - We're worth it! PMID- 8363919 TI - Nursing diagnosis: the central theme in nursing knowledge. AB - The author's purpose is to argue that theory development involving nursing diagnoses is a central element in the development of nursing knowledge. Nursing diagnosis is viewed as a way of conceptualizing the domain of nursing when human responses are viewed as a nursing focus. Differing views from the literature on what should be the central focus of nursing are presented. These authors conclude that nursing's growth as a science can be facilitated by taxonomy development as nursing diagnoses delineate nursing's unique domain. The importance of theory development surrounding nursing diagnoses is explored and ideas on how theory development might proceed are presented. Ultimately, theory supporting nursing diagnoses must account for description, explanation, prediction, and control of phenomena that nurses autonomously treat. Theory development associated with nursing diagnoses will help develop the unique knowledge base of the discipline of nursing. PMID- 8363920 TI - You make the diagnosis: The hypermetabolic state: case study. PMID- 8363921 TI - Validation of the defining characteristics of altered sexuality patterns. AB - Human sexuality is a complex and multifaceted phenomenon that encompasses physical, psychological, and social components. The nursing diagnosis altered sexuality patterns labels the human response to alterations in sexuality that occur as the result of various health problems. This validation of the defining characteristics of the diagnosis was based on a substantive theory derived from a qualitative grounded theory study. In the original study, data from 11 adult insulin-dependent diabetics living in a rural area of the Midwest were analyzed and relevant experiences conceptualized through the core concept of transforming and the supporting concept of valuing self and meeting intimacy needs. The theory was then used as a framework to formulate specific defining characteristics for the nursing diagnosis. A single diagnosis of altered sexuality has emerged that encompasses the perception of change in sexuality as well as the change itself. PMID- 8363922 TI - An axial representation of community mental health nursing diagnoses of a country at war: El Salvador. AB - This paper explores the impact of a workshop on the formulation of community mental health diagnoses in El Salvador. The author taught the process of diagnosis from the NANDA framework and explored diagnostic decision making through Caplan's Crisis Model. An epidemiologic framework was also incorporated in the diagnostic process so that host, agent, and environment could be scrutinized. The workshop resulted in the formulation of three universal community mental health diagnoses for this (then) war-torn country: depression, aggression, and anxiety; the development of a proposal for the implementation of mental health services; and an invitation to explore implementation of community mental health care services in five rural communities in El Salvador. Although the politics of El Salvador have changed, this example is typical of many Third World and war-torn countries. PMID- 8363923 TI - New diagnosis: caregiver role strain. AB - Caregiver role strain is a new diagnosis accepted by NANDA in 1992. The diagnosis is a well-described family phenomenon that can be measured and predicted. Sources of variance for the various defining characteristics have been identified. The diagnosis is also important to society. Nurses can play a significant part in reducing the role strain caregivers feel or preventing its occurrence. PMID- 8363924 TI - Sequence-selective metal ion binding to DNA oligonucleotides. AB - Metal ion titrations of several DNA oligonucleotides, 10 dodecamers and one decamer have been monitored by 1H NMR spectroscopy in order to elucidate metal ion binding patterns. Also, the effects of paramagnetic impurities on resonance linewidths and NOESY cross-peak intensities have been reversed by EDTA back titration experiments. 1H 1D NMR spectra were recorded after successive additions of aliquots of different metal salts to oligonucleotide samples. Paramagnetic manganese(II) salts were used in most cases, but a few samples were also titrated with diamagnetic zinc(II). From this study, we conclude that there exists a sequence-selective metal ion binding pattern. The metal ions bind predominantly to 5'-G in the contexts 5'-GC and 5'-GA. The order of preference seems to be GG > or = GA > GT > > GC. No evidence of metal ion binding to 5'-G in 5'-GC steps or to non-G residues was found. The H6 or H8 resonances on preceding (5'-) bases were affected by the adjacent bound paramagnetic metal ion, but no effect was observed on the protons of the succeeding (3'-) base. The metal binding site in the duplexes is most likely at G-N7, as manifested by the pronounced paramagnetic line broadening or diamagnetic shift of the G-H8 signal. This sequence selectivity may be qualitatively explained by a sequence-dependent variation in the molecular electrostatic potentials of guanine residues (MEPs) along the oligonucleotide chain. PMID- 8363925 TI - NMR studies of a plant flavonoid--DNA oligonucleotide complex. AB - A structural model of the solution complex between a flavonoid and a DNA dodecamer containing the E. coli wild-type lac promoter sequence (TATGTT) was obtained using simulated annealing for refinement. The distance constraints were derived from NOESY NMR spectra. The minor groove binding of this flavonoid displays possible hydrogen bonds to the DNA, and these can take part in complex formation. This work is the first description of how a molecule of this class of natural compounds may interact with DNA. PMID- 8363926 TI - President's message: Nursing's challenge: become a part of the solution. PMID- 8363927 TI - New policy reduces wound care reimbursement. PMID- 8363928 TI - Chronic generalized erythroderma: a guide for nurses. AB - Chronic generalized erythroderma (CGE) is a persistent, cutaneous, inflammatory response triggered by some underlying benign or malignant cause. Understanding the definition, pathogenesis, incidence, cutaneous and systemic manifestations, etiology, diagnosis, prognosis, and treatment of CGE with particular emphasis on nursing implications will help dermatology nurses care for these patients. PMID- 8363929 TI - Photodamage: cause, clinical manifestations, and prevention. AB - It is now recognized that intrinsic aging changes are distinct from those caused by habitual exposure to the sun (photoaging). Not only are these sun-induced alterations unsightly, but they also serve as a marker for patients at risk for developing skin cancer. Because of increased leisure time and affluence in our society, and an emphasis on sunbathing and other outdoor recreational activities during the last few decades, photoaging and skin cancer are becoming an ever increasing problem and source of concern for health care professionals. The purpose of this article is to review the cause, clinical manifestations, and implications of photodamage. Photoprotection and other preventive measures to minimize photoaging and the risk of skin cancer will be discussed. PMID- 8363930 TI - What's your assessment? Pigmented basal cell. PMID- 8363931 TI - Managing the patient with hives. AB - Urticaria, or hives, is a usually transient reaction involving the upper dermis. Understanding the causes and treatments of urticaria will help the dermatology nurse manage the patient with hives. PMID- 8363932 TI - Micropigmentation: a burn survivor's case study. Part 3. AB - A clinical methodology involving consultation, assessment, plan, implementation, and evaluation is important in meeting patients' skin care and cosmetic needs. Part III of this three-part series examines how this systematic and practical approach was used in camouflaging a burn survivor's appearance permanently. PMID- 8363933 TI - Dermatology Nurses' Association position statement on prevention and early detection of skin cancer. AB - The Dermatology Nurses' Association recognizes the urgent need to educate the public about the prevention and early detection of skin cancer. This position statement has been developed to serve as a guide in meeting this need. PMID- 8363934 TI - Yellow fever in 1991. PMID- 8363935 TI - Expanded programme on immunization (EPI). Poliomyelitis in 1992. PMID- 8363936 TI - A strategy to improve communication between health care professionals and people living with cancer. I. Improvement of teaching and assessment of doctor-patient communication in Canadian medical schools. AB - A task force was established by the Canadian Cancer Society and the National Cancer Institute of Canada to make recommendations aimed at improving communication between health care professionals and people living with cancer. An annotated bibliography of the research literature on the subject was commissioned by the task force. This was followed by a research workshop. With this background, the task force organized a workshop on "The Teaching and Assessment of Communication Skills in Canadian Medical Schools." Participants included expert panelists; senior faculty from all Canadian medical schools; representatives from patient and ethnic groups, faculties of nursing and social work, the Canadian licensing and accrediting bodies, the College of Family Physicians of Canada, and the Royal College of Physicians and Surgeons of Canada. A consensus statement regarding general principles, recommendations, and requirements for implementation of improved teaching and assessment of doctor patient communication in Canadian medical schools was produced and circulated widely throughout Canada. The initial response to this initiative has been positive. PMID- 8363937 TI - Teaching communication with cancer patients and terminally ill patients to medical students. PMID- 8363938 TI - A comparison of knowledge and communication skill evaluations by written essay and oral examinations in preclinical medical students. AB - While both oral and written communication skills are important in the daily work of physicians, medical school evaluation methods focus on content of written essays or often answers to multiple choice questions. To determine the feasibility and value of oral examinations for preclinical medical students, we gave a written short essay examination and an oral examination on the same question to 106 second-year medical students in a required neoplastic diseases course. Examination performance by each method was evaluated according to the same specific content and, separately, based on four communication skills criteria. We found high levels of inter-rater reliability with two oral examiners for both content and skills. Content and skills performance on both written and oral evaluations could be separately determined. Content performance was greater on the written evaluation. PMID- 8363939 TI - Use of questionable methods and physician education. AB - It is contended that medical students and physicians are not sufficiently familiar with questionable cancer methods to communicate effectively with patients, families, or the news media. A national survey by the American Cancer Society revealed that 9% of patients with cancer use questionable methods. There were substantial discrepancies between perspectives of patients and physicians. Since the physician's role is key, educational efforts are imperative for all persons involved in the care of patients with cancer. Suggestions are made. PMID- 8363940 TI - Physicians' attitudes and reported practices toward smoking intervention. AB - The objective of this study was to examine differences in the attitudes and reported practices toward smoking intervention of 224 internal medicine, family practice, and surgical physicians from one medical school faculty. Most internists and family practice physicians reported intervening with their patients who smoke, whereas only 50% of surgeons reported intervening with their patients who smoke. Each of the physician groups attached a high degree of importance to smoking cessation in patients with various chronic diseases. Physicians reported that they were most likely to intervene in the smoking habits of young patients, those with reversible disease, those who were receptive to intervention, and with those who had made previous quit attempts. The three obstacles identified by the various physician groups most related to the delivery of quit smoking intervention included the amount of time involved, patient receptivity, and associated lifestyle problems. The results of this study suggest differences among physician specialties in their intervention efforts with smokers and those factors related to the delivery of stop smoking advice. Further reinforcement of specific physician specialty groups for the important role of physicians in assisting their patients to stop smoking remains. PMID- 8363941 TI - Cancer patients' awareness of disease and satisfaction with services: the influence of their general education level. AB - Forty-five cancer patients, 22 with a low and 23 with a high general educational level, receiving chemotherapy in the chemotherapy day clinic of the Cerrahpasa Medical Faculty, were interviewed individually by a clinical psychology Master's Program student. The interview covered 45 questions about the level of their awareness of disease and treatment, prognosis, and the sources of information and whether these affected their satisfaction with the services given. The answers of the two groups with different educational levels were compared. There was no significant difference between the two groups in awareness of disease or in satisfaction with the services. However, there was significant difference between the two groups in patient-physician dialogue as to asking more and direct questions and thus in the source of information. Six attending physicians in charge of the clinic were also interviewed about their guesses on the patients' answers, and their reasons for giving different levels of information to their patients. It was suggested that general public education on the communities' concept of cancer was the most important single factor in the formation of demand and therefore revealing correct information during patient-physician communication. PMID- 8363942 TI - Communication: a crucial concern for cancer curricula. PMID- 8363943 TI - Expanding horizons in breast and prostate cancer prevention and early detection. The 1992 Samuel C. Harvey Lecture. AB - Breast cancer and prostate cancer, the most common cancers in American women and men, respectively, are major public health concerns. Investigations into the prevention and early detection of breast and prostate cancer include research on the potential impact of diet, particularly dietary fat, on breast cancer risk; the chemoprevention of breast cancer using tamoxifen and N-(4 hydroxyphenyl)retinamide(4-HPR); the importance of mammography in early detection of breast cancer; the potential of finasteride in preventing or retarding the progression of early-stage prostate cancer; and improved detection of prostate cancer by combining various screening modalities. The importance of transferring information gained though such research to the health care community cannot be overemphasized. Further, it is critical that cancer prevention and detection education be built into the curricula of leading medical and biomedical institutions. Education is key to developing a strong and vigorous cancer prevention and early detection research program. PMID- 8363944 TI - Teachers involved in AIDS training left out in the cold. PMID- 8363946 TI - Environmental health: in the wake of the Braer. Interview by Alex Mathieson. PMID- 8363945 TI - Four new cases of AIDS reported in Scotland. PMID- 8363947 TI - Community care: the cost of caring. PMID- 8363948 TI - The epidemiology of pressure sores. AB - This article presents details of epidemiological studies undertaken to assess the extent of pressure sores in hospital. Both prevalence and incidence studies, which reveal the full extent of the problem and its predisposing factors, are discussed. The author also outlines the statistical terms used by epidemiologists as well as general considerations which must be made in the interpretation of epidemiological studies. PMID- 8363949 TI - Fit or fatuous. PMID- 8363950 TI - Trends in managing schizophrenia (continuing education credit). PMID- 8363951 TI - Community nursing: nurses' effectiveness in supporting carers. AB - This article outlines the results of a research project to evaluate the effectiveness of service support to informal carers. There are many ways in which community nurses can support carers, and carers frequently report the benefits of the service. The potential significance of the community nursing service in this role, however, is yet to be realised as nursing is still highly task-orientated, with priority given to specific medical interventions. As a result, some carers face difficulties in obtaining nursing support. PMID- 8363952 TI - A study on the nursing care of HIV positive and AIDS patients. PMID- 8363953 TI - Community care: what price means-testing? PMID- 8363954 TI - De-stress call. The Rosemary Cook column. PMID- 8363955 TI - Dissect your managers. PMID- 8363956 TI - A qualified 'yes' to nursing. PMID- 8363957 TI - Should we deny people with learning difficulties their childlike indulgences. PMID- 8363958 TI - Is this mental health nursing's last stand? PMID- 8363960 TI - Today's lifestyles affect elderly care. PMID- 8363959 TI - New report highlights neglect of older people with HIV/AIDS. PMID- 8363962 TI - A philosophy of care. PMID- 8363961 TI - AIDS education. Getting sex taped. PMID- 8363963 TI - Clinical grading: quids in or quids out? PMID- 8363964 TI - The health of the nation: the path to good health. PMID- 8363965 TI - Teaching psychology: the Australian view. AB - Teaching psychology to student nurses has assumed great importance in recent years. Making the course applicable to clinical practice, however, remains a challenge. The authors discusses techniques being used in Australia to make psychology relevant to nursing and highlights aspects which could be adopted in the UK. PMID- 8363966 TI - Statistical tests (Part 2): Parametric tests. PMID- 8363967 TI - Care of urinary catheters (continuing education credit). PMID- 8363968 TI - Intubation training: an ethical practice? AB - Some hospitals allow junior doctors, nurses and paramedical staff to practise the technique of intubation on recently deceased patients. The Royal College of Nursing, in common with the British Medical Association, believes that this practice can only be justified in the most exceptional circumstances where the deceased patient has suffered severe head, neck or facial injuries. It may then be acceptable for learners already skilled in intubation techniques to extend their knowledge for the benefit of future patients with similar injuries who might, as a result, have a prospect of survival. PMID- 8363969 TI - Computer reviews. The travel program. PMID- 8363971 TI - Cardiology update. Emergency bypass. PMID- 8363970 TI - Cardiology update. Resuscitation update. PMID- 8363972 TI - Cardiology update. Intraosseous infusion. PMID- 8363973 TI - The influence of amitriptyline and flunarizine on catecholamine response to light in patients with migraine. AB - The effect of amitriptyline on catecholamine (CA) response to light of 20 migrainous patients was studied. The drug was given orally, 36 mg daily (12 mg x 3), for ten days. Before therapy, the migraineurs responded to light by an increase in epinephrine (E) excretion and not by the rise in norepinephrine (NE) excretion, noticed in controls. The NE excretion of migrainous subjects underwent very often a depression after photostimulation. Amitriptyline therapy prevented the post-photic rise in E excretion of migraineurs, without influencing significantly the variation in NE excretion produced in them by light. In other 8 migrainous subjects the effect of flunarizine, a selective calcium channel blocker, on CA response to light was tested. The dosage was of 5 mg daily, for ten days. Flunarizine had similar effects to those displayed by amitriptyline; the drug prevented the rise in E excretion produced by light without normalizing the NE response to light of migrainous subjects. The results suggest that the efficiency of these two drugs in migraine prophylaxis is connected with the ability of these substances to block the E discharge produced in migraineurs by light or by other stimuli. The interpretation is all the more likely as propranolol, another drug applied in migraine prophylaxis also blocks the post photic E discharge of migraineurs. PMID- 8363974 TI - Pseudotumor cerebri. A review. PMID- 8363975 TI - Clinical, polysomnographic and computerized electroencephalographic research in temporal lobe epilepsies. AB - The present study has selected 125 cases with psychomotor attacks (sometimes secondarily generalized). Polysomnographic recordings were carried out for a continuous period of eight hours. All this time, the patients have been observed by video-monitorization on a closed infrared circuit screen. The diagnostic procedure was supported by several computerized EEG mappings (CEM) according to a model achieved by us, transcribing the primary data which were obtained by Hjorth's NSD parameters (activity and ability) from the Siemens-Elema Mingograph to a microcomputer. In many cases, we have employed an interface which had been envisaged by us for analog-digital conversion of amplitudes and frequencies from the Mingograph to the microcomputer. Sleep organization anomalies were found: increase of the percentages of light slow-wave sleep (LSWS) and of REM sleep and reduction of the percentages of deep slow-wave sleep (DSWS). The temporal foci appeared with the greatest frequency and with a clear-cut evidence during LSWS, especially in REM sleep and in the transitional states of SWS to REM sleep and from REM sleep to wakefulness. Our researches supplemented with CEM, demonstrate a peculiar activation of the temporal foci during REM sleep, during the states of LSWS and during the transitional states, showing that many psychomotor attacks appear predominantly during these sleep states and that many cases initially clinically misinterpreted as grand mal seizures are, in fact, focal temporal epilepsies secondarily generalized. PMID- 8363976 TI - Genomic imprinting and fragile X-syndrome in psychiatric disorders. PMID- 8363977 TI - Polysomnographic and computerized electroencephalographic studies in myoclonic petit mal epilepsies. AB - The study included 203 epileptic absences: 1. Simple; (30 cases); 2. Myoclonic petit mal absences (62 cases); 3. Amyotonic-akinetic absences (41 cases); 4. Temporal lobe absences (62 cases); 5. "Hybrid" absences in Lennox-Gastaud disease (13 children). This paper presents only the myoclonic petit mal absences (57 cases). Correlations of the clinical, EEG and polysomnographic data were found by several methods: a. The patients were video-monitored on an infrared closed circuit TV screen: b. The Hjorth's NSD parameters were computed on a Siemens Elema Mingograph; c. The EEG graphoelements were morphologically analyzed every second throughout the discharges, by means of an original technique; d. Computerized EEG mappings (CEM) were performed for various periods, also including the sequential ones, second by second, all along the epileptic discharges; e. 8 hours of continuous polysomnographic recordings. The peculiar electroclinical features of the five types of absences have been emphasized. Regarding the myoclonic petit mal absences, the discharges of polyspikes and waves manifested an evident increase in the number and duration within the LSWS stages and during the transition from the wakefulness state to sleep and from the LSWS to the wakefulness, and a transformation in slow polyspikes and waves complexes during the stages III and IV. The CEM were always asymmetrical during sleep and the maximal amplitudes were seen on the anterior and posterior temporal regions. In all the REM stages, the polyspikes and waves disappeared. PMID- 8363978 TI - Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency. AB - The present paper reports biochemical and neurophysiological investigations in ten cases with restless leg syndrome. Other neuropsychiatric affections and factors which could generate the symptomatology of restless legs syndrome were not included. The EEG recordings demonstrated evident reticular neuronal hypersynchrony generated by hyperpnoea (sinusoidal slow waves). The classical EEG investigations pointed out neuromuscular hyperexcitability, but some modifications of the functional parameters of the neuromuscular excitability and conductibility (signs of neuropathy) were also noticed. In all the cases, continuous 8-hour polysomnographic recordings and monitorization on infrared TV screen were performed. Investigations reported: important disorders of sleep organization, agitated sleep with frequent periods of nocturnal awakenings, increase of the durations and percentages of light slow-wave sleep (LSWS) and rapid and frequent changes of various stages of LSWS, a decrease of duration and percentage of DSWS, a decrease of duration and percentage of REM sleep (as in other parasomnias caused by magnesium deficiency) and nocturnal EEG anomalies (long discharges of sinusoidal slow waves, of sharp waves and of sharp slow waves appearing in the LSWS stages with the disappearance in the REM sleep). PMID- 8363979 TI - Subacute subdural hematoma. AB - The subacute subdural hematoma (SASDH) is an entity which is still to be analyzed because the attention of the clinicians was directed towards the acute subdural hematoma (ASDH) and to the chronic subdural hematoma (CSDH). A series of 69 patients with SASDH was studied outlining the particularities of the affection. A trauma caused the hematoma but it was a milder one. The associated cerebral lesions were generally produced by concussion (34%) and cerebral dilacerations represented only 8.4%. Clinical symptoms were obvious between the third and the fourteenth day after trauma due to the cerebral compression. The consciousness was moderately impaired. The patients with GCS < 8 represented 18.9%. The neurological picture stated with time allowed a programmed paraclinical investigation: a. radiography of the skull revealed cranial fractures in 10.1%; b. carotid arteriography showed a lentiform aspect of the avascular space; c. CT presented variable densities (isodensity--3%, hypodensity--14.5%, and hyperdensity--27.5%) depending on the length of the interval between trauma and admission. The operation evacuated the liquid blood collection through a widened burr hole. Death during operation was 17.4% and 79.8% survived. PMID- 8363980 TI - British Association of Dermatologists and Canadian Dermatology Association, joint annual meeting. Oxford, United Kingdom, 6-10 July 1993. Abstracts. PMID- 8363981 TI - Critical analysis of the methods commonly employed in the assessment of cell proliferation: advantages of the NOR silver-staining technique in routine cyto histopathology. AB - The methods commonly employed for the assessment of cell proliferation have been critically considered. Some 'historical' techniques, such as the mitotic count and the thymidine labeling index, cannot be proposed for routine pathology because of their complexity and difficult quantification. Other techniques, such as in vitro bromodeoxyuridine incorporation or in vivo bromodeoxyuridine infusion coupled with DNA flow cytometry, permit a very sophisticated analysis of the tumour cell kinetics, but can be performed only in highly specialized centers. During the past few years the immunohistochemical detection of antigens related to the cell cycle--particularly Ki67 or proliferating cell nuclear antigen (PCNA)/cyclin--has been rapidly introduced in numerous laboratories, and, at present, certainly represents the most common method for the assessment of cell proliferation in tumour samples. However, a new marker of cell proliferation has been recently described which presents technical features particularly suitable for routine use: the quantitative evaluation of interphase silver-stained nucleolar organizer regions (AgNORs). The NOR silver-staining technique is simple, very rapidly executed, inexpensive, easily quantifiable and, most important, can be performed on routinely processed cytological and histological samples. PMID- 8363982 TI - Pattern of nucleolar organizer regions in human leukemic cells. AB - The pattern of nucleolar organizer regions in bone marrow smears of 40 patients with acute myeloid leukemia (AML), 27 with acute lymphoid leukemia (ALL) and 15 control cases were studied. All normal blasts as well as leukemic blasts revealed at least one cluster of AgNORs. In AML the mean number of clusters (2.87 +/- 0.48) and dots (0.23 +/- 0.17) per cell was significantly lower than in normal myeloblasts (3.27 +/- 0.14 resp. 0.34 +/- 0.12). In ALL the number of clusters (2.82 +/- 0.62) was not significantly different from that of AML blasts. While in all control cases the distribution of the number of clusters per cell within a case could be approximated by a modified Poisson equation, this did not hold for 9 ALL and in 13 AML patients. The histogram of those cases showed a lower dispersion. In ALL, but not in AML, the number of clusters per cell correlated with the peripheral leukocyte count. The present results strengthen the concept that clusters and dots should be regarded as separate entities and suggest that their pattern is related to duration of cell cycle as it has been shown in other tissues. PMID- 8363983 TI - Minimum spanning tree, integrated optical density and lymph node metastasis in bronchial carcinoma. AB - Surgical specimens comprising 80 primary lung carcinoma (lobes and lungs) were expanded by insufflation of air into the main bronchi, and fixed with buffered formalin for 24 h. After the usual tissue procedures, 3-4 microns thick histological sections of the tumour mass were Feulgen stained and various nuclear features such as integrated optical density (IOD), area, form factor, etc. were measured using an automated image analysing system (VISIAC). The geometrical centres of the nuclei were defined as vertices and the corresponding minimum spanning tree (MST) was calculated according to the distance between the vertices. The tumour mass was measured by serial sections of the surgical specimens; the lymph node stage was defined according to the rules of the UICC. Non-tumour infiltrated lymph nodes of the same case served as controls for the IOD and MST. The results revealed a DNA index of 1.1-3.0, a malignancy index (Bocking) 0.90-1.08 and a percentage of S-phases 10-23% (confidence limits). Only 19% of the bronchial carcinoma were found to be not aneuploid. Based upon the weighted MST, the distance of neighbouring cells, the IOD of the centre cells and IOD/area of neighbouring cells revealed statistically significant differences between tumours with and without lymph node metastases. The more advanced the lymph node stage, the 'closer' was the 'packing' of the tumour cells. PMID- 8363984 TI - Non-distorted assemblage of the digital images of adjacent fields in histological sections. AB - In the following article a method is described for the distortion-free reassemblage of adjacent digitised microscopic images of histological sections. The correct positioning of the microscopic specimen is achieved via a computer controlled scanning stage. During an internal calibration step the correction function for the image distortions and the parameters of the transformation scanning-stage-to image-coordinate system are determined. In the subsequent application phase the new positions the scanning stage has to move to can now be computed in such a way that the distortion-corrected digitised images of the section parts under consideration neatly fit together to one composite image. PMID- 8363985 TI - Detection of the Ki-67 antigen in fixed proliferating cells. PMID- 8363986 TI - Adhesion molecules: cellular recognition mechanisms. The Pezcoller Foundation Symposia, Rovereto, June 24-26, 1992. PMID- 8363987 TI - The take-home message: doctors' views on letters and tapes after a cancer consultation. AB - BACKGROUND: Patients' understanding of their disease and treatment varies in detail and accuracy. In order to participate in decisions about their care patients must understand, evaluate and retain complex information. METHODS: We canvassed doctors' views about the use of individualised letters and the use of audiotapes of the initial cancer consultation to improve doctor-patient communication. The study sample consists of doctors whose patients participated in a trial of the latter technique. RESULTS: One hundred sixty of 194 doctors (82%) responded to a mailed questionnaire. Sixty-one percent of respondents felt that providing patients with a tape of their initial cancer consultation would be beneficial, and 71% felt that an individualised letter would be better. General practitioners were more supportive of providing tape recordings to patients than were specialists (p = 0.057), but both groups favoured letters over tapes. Specialists were more concerned about the risks of providing tapes to patients than were general practitioners (p = 0.001), but only 13% of respondents felt that the risks were prohibitive. DISCUSSION: Wide support for providing individualised letters or tapes to patients, and copies to their doctors, indicate that the doctors surveyed believe that both doctor-patient and doctor doctor communication could be improved by the use of these techniques. PMID- 8363988 TI - Suramin in combination with mitomycin C in hormone-resistant prostate cancer. A phase II clinical study. AB - BACKGROUND: Hormone-resistant prostate cancer can respond to mitomycin C or to suramin. This trial was undertaken to investigate the value of mitomycin C given with low dose suramin. PATIENTS AND METHODS: Thirty-two patients with hormone refractory prostate cancer were given suramin 350 mg/m2 daily for 5 days, followed by 350 mg/m2 weekly starting on day 14. Mitomycin C 12 mg/m2 was given every 5 weeks starting on day 14. RESULTS: Toxicity included maculo-papular skin rash in 8 patients, haematological toxicity in 16 (anaemia 13, leucopenia 11 and thrombocytopenia 9, bleeding 8), infection in 4 and fatigue in 11. Ten patients developed neurotoxicity, (temporary sensory peripheral neuropathy in 8, upper limb motor neuropathy in 1, and restless legs syndrome in 1) and 9 developed proteinuria. Other toxicities were mild nausea and vomiting, oedema, transient elevation of liver enzymes, stomatitis, upper gastrointestinal symptoms, and alopecia. During induction treatment the median trough suramin level was 140 micrograms/ml (range 100-273) and during maintenance treatment the median suramin level was 93 micrograms/ml. The median overall trough level was 93 micrograms/ml. There were one complete and 6 partial responses. Fifteen patients had disease stabilization. The median time to treatment failure was 103 days, and the median survival 209 days. CONCLUSION: The combination of suramin and mitomycin C has therapeutic activity, but causes significant toxicity in patients with hormone resistant prostatic carcinoma. PMID- 8363989 TI - Fludarabine: an active agent in the treatment of previously-treated and untreated low-grade non-Hodgkin's lymphoma. AB - BACKGROUND: Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with a promising therapeutic activity in the lymphoproliferative disorders. PATIENTS AND METHODS: We performed a phase II study with this drug in previously untreated and treated patients with resistant and/or relapsed low-grade non-Hodgkin's lymphoma (LG-NHL) to determine its response rate. Twenty-one patients were treated at a dosage of 25 mg/m2 per day for 5 consecutive days. RESULTS: Of the 21 patients, 3 achieved complete responses (CR) and 11 partial responses (PR). In addition, three patients obtained minor responses, and the remaining 4 showed no benefit from the treatment. An increased response rate was achieved in 8 untreated patients in which 3 CR and 3 PR were documented. Furthermore, 4 of the 5 patients showing a leukemic blood picture experienced significant reductions of lymphocyte count and 2 patients with macroglobulinemic lymphomas experienced significant reductions of the IgM monoclonal component from 7.8 and 5.9 g/100 mL to 1.0 and 1.1 g/100 mL, respectively. The toxicity on platelets was negligible. The major toxic effects observed were neutropenia (62%) and infections and/or febrile episodes (19%) that were fatal to only one patient. CONCLUSIONS: In consideration of its significant activity, the role of FLU needs to be further evaluated in the management of pretreated and untreated patients with LG-NHL. PMID- 8363990 TI - The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-alpha using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: a pilot study. AB - BACKGROUND: 5-Fluorouracil (5-FU) is the most widely used cytotoxic drug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. PATIENTS AND METHODS: Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. RESULTS: Twenty-six patients were treated with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon alpha (p = 0.007). CONCLUSIONS: MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue metabolism of a fluorinated drug is of interest. PMID- 8363991 TI - Fever and neutropenia during intensive chemotherapy. PMID- 8363992 TI - Phase II trial of mitomycin C (MMC) in advanced gallbladder and biliary tree carcinoma. An EORTC Gastrointestinal Tract Cancer Cooperative Group Study. AB - BACKGROUND: Based on a recent pharmacokinetic study suggesting that high biliary levels of mitomycin C (MMC) may be achieved as a result of an entero-hepatic recycling mechanism, we conducted a Phase II EORTC trial which involved MMC administration to patients with non-resectable biliary tract carcinoma. PATIENTS AND METHODS: Of the 34 patients entered in the study, 30 were eligible (11m + 19f, median age 58 yrs). I.V. bolus injections of 15 mg/m2 MMC were administered at six-week intervals. The tumors were confined to the liver in 17 patients and 13 had extra-hepatic localizations. RESULTS: All 30 eligible patients were evaluable for toxicity and response. Mild thrombocytopenia was the main toxic side effect. Severe, WHO grade III/IV thrombocytopenia was limited to 4 patients. The haemolytic uraemic syndrome was not observed and there were no toxic deaths. Of 30 patients, 3 had partial remissions (overall response 10%, 95% confidence interval 2%-27%). CONCLUSIONS: This study, the largest such ongoing phase II trial, shows no significant activity of single-agent MMC in patients with advanced biliary tract carcinoma. PMID- 8363993 TI - Pharmacology, toxicology and human pharmacokinetics of tropisetron. AB - Tropisetron is a novel, potent and highly selective 5-HT3 receptor antagonist, which is active in the treatment of nausea and vomiting induced by highly emetogenic chemotherapeutic drugs such as cisplatin. Tropisetron selectively blocks the excitation of the presynaptic 5-HT receptors of the peripheral neurones involved in the emetic reflex, and may have other direct actions in the CNS on 5-HT3 receptors, mediating the actions of vagal inputs to the area postrema. Toxicological studies show that tropisetron is generally well tolerated by all animal species investigated and no specific organ toxicity was observed, other than slight loss of body weight development. In man, tropisetron metabolism is linked to the cytochrome P-450 2D6 isoenzyme system, which determines the polymorphism of debrisoquine/sparteine metabolism. As a result, there are phenotypical populations of extensive and poor metabolizers. The two main adverse events in human volunteer tolerability studies with tropisetron were headache and constipation. These adverse events tended to be slightly more intense and to last longer in poor metabolizers, compared with extensive metabolizers. Tropisetron had similar pharmacokinetic characteristics in elderly patients and renal patients, compared with healthy subjects. From a toxicological and pharmacokinetic point of view, therefore, daily doses of 5 mg tropisetron can be administered to both poor and extensive metabolizers, as well as to special populations, without any particular precautions. PMID- 8363994 TI - The development of tropisetron in its clinical perspective. AB - This review discusses the development of tropisetron as an antiemetic drug with the patient in mind. The original aims of the programme and the progress achieved towards them to date are described. The efficacy and safety data from two dose ranging studies and four comparative-treatment studies with tropisetron were combined in a prospectively planned meta-analysis of 799 patients. An integrated safety summary is presented which includes all patients from the six studies. Tropisetron at a dose of 5 mg once daily is an effective and well-tolerated, single-agent, antiemetic treatment, which can be given without special precautions to all patients receiving highly emetogenic chemotherapy. In comparison with metoclopramide, tropisetron is more effective in the prevention of nausea and vomiting. When compared with the most potent cocktail treatments currently in use (containing high-dose metoclopramide, dexamethasone and lorazepam or diphenhydramine), tropisetron is equally effective in the prevention of acute vomiting and somewhat less effective in the prevention of nausea. Overall, tropisetron is an effective and well-tolerated antiemetic treatment that is simple to administer, comparing well with currently available antiemetic cocktails. Tropisetron remains effective for the prevention of nausea and vomiting during multiple chemotherapy courses. The simple dosing schedule (5 mg i.v. day 1; one 5 mg capsule daily, days 2-6) makes tropisetron ideal for both inpatient or outpatient use. PMID- 8363995 TI - Tropisetron in the prevention of chemotherapy-induced nausea and vomiting in patients responding poorly to previous conventional antiemetic therapy. AB - An open, two-armed, multicentre trial was conducted in 231 patients with malignant disease who had previously failed to respond to conventional antiemetic treatment for the prevention of chemotherapy-induced nausea and vomiting. Patients were randomized to receive either tropisetron (5 mg/day; n = 115) or a standard antiemetic therapy, which was considered optimal for each individual but did not include a 5-HT3 receptor antagonist (n = 116). Acute vomiting on Day 1 was controlled in 60 (52%) tropisetron patients, compared with only 29 (25%) patients receiving optimal standard therapy (p < 0.001). Acute nausea was completely inhibited in 37 (32%) tropisetron patients, compared with 22 (19%) patients on optimal standard therapy (p < 0.05). On Day 1, delayed vomiting was also significantly better prevented by tropisetron (p < 0.001). Side effects from tropisetron (headache and constipation) were mild, and no extrapyramidal symptoms were observed in any tropisetron patients, in contrast, to 14 (13%) patients in the 'optimal standard' group. In conclusion, in cases of acute nausea and vomiting it is more effective to switch refractory patients to tropisetron rather than attempt to optimize the dose of standard antiemetic therapy. For delayed nausea and vomiting, combination antiemetic therapy, with differing types of receptor antagonism and corticosteroids may provide the best way forward. Such studies are in progress. PMID- 8363996 TI - Current issues in the management of nausea and vomiting. AB - This state-of-the-art review describes the development, over the past 12 years, of new agents for the control of chemotherapy- and radiotherapy-induced emesis. While the mechanism of chemotherapy-induced nausea and vomiting is still not fully understood, significant progress in prevention of the symptoms has been achieved. The discovery that high-dose metoclopramide was very effective in antiemetic control ultimately led to the development of a new class of antiemetics, the 5-HT3 receptor antagonists, of which tropisetron is the most recent to be introduced. The emphasis of the review is on acute chemotherapy induced emesis and includes current thinking on the influence of patient characteristics on the emetic outcome. The new 5-HT3 receptor antagonists do not demonstrate any of the distressing extrapyramidal reactions so frequently encountered with conventional antiemetics acting at dopamine receptor sites. Mild headache is the most characteristic side effect of this class of agents. The major advantages of the newer 5-HT3 receptor antagonists, such as tropisetron, over the conventional antiemetic regimens are convenience, flexibility and, above all, single-dose usage. PMID- 8363997 TI - Efficacy and tolerability of tropisetron and dexamethasone in the control of nausea and vomiting induced by cisplatin. AB - A multicentre study was performed at four oncology centres in Sweden, in 160 chemotherapy-naive women, primarily with ovarian or endometrial carcinomas. Abdominal surgery preceded chemotherapy in 146 (91%) women, and another 39 (24%) women had a history of radiotherapy. The chemotherapy regimens contained cisplatin (50-100 mg/m2), in combination with a variety of other agents. In Course 1, all patients received tropisetron (5 mg i.v. Day 1; 5 mg p.o. Days 2-6) and 84% of patients achieved total or partial control of vomiting; 95% of patients achieved total or partial control of nausea during the first 24 hours. Vomiting was least successfully controlled on Day 2 (73% total or partial control) and Days 2-4 for the control of nausea (81, 83, 88% total or partial control, respectively). Patients with partial response in Course 1 (39% of patients) were randomized to addition of dexamethasone or placebo in Course 2. In Course 2, tropisetron plus dexamethasone (Group B2) prevented acute vomiting in 75% of patients, compared with 40% of patients receiving tropisetron plus placebo (Group B1). Over the entire 6 days, there was no vomiting at all in 54% and 20% of B2 and B1 patients, respectively. In Course 2, acute nausea was prevented in 75% of patients (receiving B1) and in 37% of patients (receiving B2). For nausea, over the complete 6 days, the figures were 64% and 3% (p < 0.001). This indicated that patients with incomplete control of emesis in Course 1 benefited from the addition of dexamethasone, provided that it was added for each of the 6 days studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8363998 TI - Tropisetron in the control of nausea and vomiting induced by combined cancer chemotherapy in children. AB - The efficacy of tropisetron, a new 5-HT3 receptor antagonist, was evaluated in a group of 15 children with a variety of malignant tumours. The majority of children (14/15) received fractionated chemotherapy and on day one complete control of acute nausea and vomiting was observed in 68.7% of all patients with a single, 15-minute, i.v. infusion of tropisetron. Partial control of vomiting was observed in 25% of patients and of nausea in 31.3% of patients on Day 1. Complete control of delayed nausea and vomiting was more variable, with an observed range between 50%-81% of patients over Days 2-6. There was no loss of appetite in 75% of patients treated with tropisetron on Day 1 and, more variably, in 62%-87% of patients on Days 2-6. Side effects were recorded in 18.8% of chemotherapy cycles, the most significant being insomnia in 12.5% of cycles and slight fever in 6.3% of cycles. It was concluded that tropisetron was well suited for children and could be recommended for those receiving a high burden of fractionated chemotherapy. PMID- 8363999 TI - Tropisetron in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience. AB - An open, non-comparative, Nordic multicenter study was performed during 1991-1992 to evaluate the new 5-HT3 receptor antagonist tropisetron, as an antiemetic agent in various types of cancer chemotherapy. More than 600 patients were recruited from 16 cancer centers in Sweden, Finland and Denmark. In this report an interim analysis on 231 patients is presented. Gynecological cancers (61%), lung cancer (14%) and breast cancer (7%), were the main diagnoses. In 118 of 231 patients (51%) prior experience of chemotherapy was documented. In 91 patients (39%) cisplatin was part of the cytostatic regimen. Carboplatin (27%), doxorubicin (32%), epidoxorubicin (18%) were also frequently included. In all, 18 cytostatic agents were studied. The median number of courses studied was 3.3 (range 1-15). Overall 153 of 231 patients (67%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting (Days 2-6) were completely controlled in 45%-72%. Treatment efficacy remained stable (57%-89%) over 10 consecutive courses of chemotherapy. For non-cisplatin regimens complete protection was achieved in 78% compared with 51% for cisplatin regimens (p < 0.0001). Patients with no prior experience of chemotherapy had greater control of acute nausea and vomiting (73%) than patients treated before (61%) in the first course, but not in subsequent courses. There were no such differences in control of delayed nausea and vomiting between chemotherapy-naive and previously treated patients. Sex and age were significant prognostic factors with regard to antiemetic response. Adverse events were recorded in 19%-36% of the cases during long-term follow-up. Headache (16%) and constipation (5%) were most frequent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364000 TI - Compassionate use of tropisetron in patients at high risk of severe emesis. AB - Tropisetron is a 5-HT3 receptor antagonist which suppresses nausea and vomiting induced by cancer chemotherapeutic agents. In this study, tropisetron was evaluated on a compassionate-need basis in 545 cancer patients who had either proved refractory to antiemetic treatment during previous chemotherapy or who were at high risk of emesis as a result of current therapy. Tropisetron (5 mg or 10 mg) was administered as a 15-minute infusion prior to chemotherapy, with the further possibility of an additional dose, either orally or parenterally, on one or more subsequent days. In some patients the drug was administered orally on the day before treatment. On Day 1 of Course 1, 64.7% of patients had a complete response to tropisetron, i.e. no nausea or vomiting, and 26.9% of patients had a partial response. More than 80% of patients with a complete response in Course 1 had a complete response in Course 2 and of the partial responders in Course 1, 37% achieved a complete response in Course 2. Of the 7.6% failures in Course 1, a further 26% achieved a complete response in Course 2. Tropisetron was well tolerated, with adverse effects recorded in only 45 (8%) patients. PMID- 8364001 TI - Pharmacological control of hypertriglyceridemia. AB - Hypertriglyceridemia has been recently recognized as a vascular risk factor, based on both clinical and experimental findings. Epidemiological studies clearly showed that elevated plasma triglycerides in subjects with low high-density lipoprotein (HDL) cholesterol (<35 mg/dl) and/or a low-density lipoprotein (LDL)/HDL cholesterol ratio > 5 are associated with an elevated risk for coronary heart disease (CHD), while intervention studies indicate that triglyceride lowering with drugs may lead to a significant CHD reduction. Elevated blood triglycerides are associated with major alterations in the structure/function of plasma lipoproteins, which become more atherogenic, and with abnormalities in the clotting system, which may predispose to coronary thrombosis. New criteria for the classification of hypertriglyceridemias and a stepwise approach to the management of patients with elevated plasma triglycerides have been recently developed. Nonpharmacological interventions, i.e., weight reduction, alcohol and smoking cessation, and physical exercise, are the first-line actions to control hypertriglyceridemia. Drug therapy should be considered when the nonpharmacological approaches are ineffective or inadequate. Fibric acid derivatives and nicotinic acid (and its derivatives) are the drugs of choice when treating hypertriglyceridemic patients; n-3 fatty acids (fish oil) and metformin (especially in diabetic patients) represent additional therapeutic agents. PMID- 8364002 TI - Effect of dobutamine on left ventricular relaxation and filling phase in patients with ischemic heart disease and preserved systolic function. AB - The beneficial effects of dobutamine on left ventricular systolic and diastolic phases have been described in patients with congestive heart failure. Its influence on left ventricular diastolic phase in patients with preserved systolic function, absence of dys- or akinetic areas, and left ventricular dilatation has not yet been adequately investigated. Thus a simultaneous echo-Doppler and hemodynamic study was performed in 15 patients with ischemic heart disease and preserved systolic function in order to assess the effect of dobutamine on left ventricular relaxation and filling phase. The infusion of dobutamine at a rate of 10 micrograms/kg/min induced a marked inotropic action, as shown by the significant increase in positive dP/dt (from 1392 +/- 224 to 2192 +/- 295 mmHg/sec, p < 0.001), dP/dt/P (from 32 +/- 8.1 to 50 +/- 17 sec-1; p < 0.0001), and in peak of systolic pressure (from 143 +/- 25 to 168 +/- 36 mmHg; p < 0.005). In addition, dobutamine reduced the end-systolic volume index (from 30 +/- 16 to 26 +/- 19 ml/m2; p < 0.05), the end-systolic stress (from 222.2 +/- 65.3 to 198.4 +/- 84 g/cm2; p < 0.006), and had favorable effects on relaxation and the early filling phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364003 TI - Hemodynamic effects of prolonged enoximone infusion (7 days) in patients with severe chronic heart failure. AB - This study investigated the hemodynamic effects and tolerance of infusion of 10 micrograms/kg/min enoximone over 7 days in 12 patients (mean age 64.3 years) with severe chronic heart failure (10 NYHA Class III and 2 Class IV) with idiopathic dilated cardiomyopathy. Hemodynamic parameters were measured 10 minutes, 3 hours, 6 hours, 18 hours, 24 hours, and 7 days after the start of infusion. Catecholamines were assayed before the start of the infusion and on day 7. The heart rate increased on an average from 90.8 +/- 13.7 before infusion to 108.5 +/ 8.2 beats/min (p < 0.05) on day 7 (+20%). The mean arterial pressure decreased by approximately 10% (p < 0.05) between the start and end of the infusion. The pulmonary artery diastolic pressure dropped by a maximum of 30% at the 24th hour (23.1 +/- 5.1 to 16 +/- 5.4 mm Hg; p < 0.01). This decrease remained significant on day 7; the index cardiac was increased a maximum of 40% between the 18th and the 24th hour; p < 0.01). This increase was still significant on day 7 (2.35 +/- 0.44; p < 0.05; +22%). Finally, the decrease in systemic arterial resistance, which reached a maximum of 30% of the 24th hour, persisted on day 7 (-22%); 2076 +/- 451 to 1612 +/- 283 dynes/sec/cm5; p < 0.05). The norepinephrine level did not change significantly (4.5 +/- 1.2 nmol/l before infusion vs. 4.2 +/- 1.1 nmol/l on day 7). Infusion had to be stopped in one patient after 30 minutes because of prolonged severe hypotension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364004 TI - Effect of enoximone alone and in combination with metoprolol on myocardial function and energetics in severe congestive heart failure: improvement in hemodynamic and metabolic profile. AB - The hemodynamic and myocardial metabolic effects of enoximone (phosphodiesterase III inhibitor), alone or in combination with metoprolol (beta-adrenergic blocker), were studied in patients with congestive heart failure. Ten patients (New York Heart Association Class III-IV) underwent right heart and coronary sinus catheterization, and parameters were assessed at basal condition, at peak enoximone response (mean intravenous loading dose = 2.2 mg/kg), and after the combination with metoprolol (mean intravenous dose = 8.5 mg). Heart rate tended to increase during enoximone administration (from 102 +/- 16 to 107 +/- 16 min-1, ns) and was reduced during enoximone plus metoprolol (to 88 +/- 15 min-1, p < 0.05 vs. basal). Cardiac index was increased during enoximone (from 2.2 +/- 0.2 to 3.8 +/- 0.5 1/min/m2, p < 0.05) and decreased during enoximone plus metoprolol (to 2.8 +/- 0.5 1/min/m2, p < 0.05 vs. enoximone). Mean pulmonary wedge pressure fell during enoximone and remained reduced during enoximone plus metoprolol (from 27 +/- 9 to 9 +/- 3 and to 13 +/- 4 mmHg, respectively, both p < 0.05). Myocardial oxygen consumption did not change during enoximone (from 27 +/- 8 to 25 +/- 13 ml/min, ns) and was reduced during enoximone plus metoprolol (to 19 +/- 8 ml/min, p < 0.05 vs. basal). Myocardial lactate extraction tended to be lower during enoximone and during enoximone plus metoprolol conditions (from 38 +/- 17% to 26 +/- 20% and to 29 +/- 24%, respectively), but no statistical significance was found. Myocardial efficiency was increased during enoximone and during enoximone plus metoprolol (from 9 +/- 3% to 15 +/- 6% and to 14 +/- 6%, respectively, both p < 0.05). Thus in patients with congestive heart failure enoximone improves hemodynamics and, in most cases, it does not influence energetics. The addition of metoprolol to enoximone reduces heart rate, cardiac index, and myocardial oxygen consumption without any other major changes, producing a more physiologic hemodynamic and metabolic profile. PMID- 8364005 TI - Assessment of the cardiostimulant action of propionyl-L-carnitine on chronically volume-overloaded rat hearts. AB - Chronic volume overload was induced in young rats of Wistar strain by surgical opening of the aorto-caval fistula. Three months later, during in vitro perfusion with exogenous palmitate, left ventricular function and energy turnover (QO2) of hypertrophied hearts were severely depressed. This seemed to be related to impaired long-chain fatty acid utilization, as reflected by decreased 14CO2 production from U-14C-palmitate and decreased tissue levels of L-carnitine. Another group of rats exposed to chronic volume overload was pretreated for 2 weeks before sacrifice with propionyl-L-carnitine (250 mg/kg/day), and the hearts were perfused with 1.2 mM palmitate and 10 mM propionyl-L-carnitine. In this group, both mechanical performance and the oxygen consumption rate were quite comparable to those of untreated controls. On the other hand, tissue levels of L carnitine were only slightly increased, and the rate of 14CO2 production from U 14C-palmitate was insignificantly improved. This suggests that propionyl-L carnitine administration promotes the mechanical performance of normoxic volume overloaded hearts via a mechanism other than improved palmitate utilization. The possibility that propionyl moieties themselves replenish with mitochondrial intermediates of the tricarboxylic cycle (malate, acetyl-CoA) is not excluded. PMID- 8364006 TI - Electrophysiological effects of flecainide acetate on stretched guinea pig left atrial muscle fibers. AB - The electrophysiological effects of flecainide acetate (3 x 10(-6) M) on stretched atrial tissue were investigated using guinea-pig left atrial muscle fibers. Before stretching, the resting membrane potential was not affected by flecainide at 1 Hz, although the overshoot potential (Eov) and the action potential duration at 50% repolarization (APD50) were slightly but significantly decreased by 2 +/- 1 mV and 2 +/- 1 msec, respectively. The effective refractory period (ERP) was increased by 3 +/- 1 msec. The reduction of Vmax was 20.6 +/- 1.2%. The half-maximum potential (Vh) of the relationship between Vmax and the resting potential was shifted to become more negative by flecainide (from -60.6 +/- 2.1 mV to -63.2 +/- 1.7 mV). After 90-120 min of washout with drug-free Tyrode's solution, the tissue was mechanically stretched to 150% of its slack length. Stretching significantly decreased the Vmax by 16.9 +/- 3.1%, along with a slight but significant increase in ERP (3 +/- 1 msec) and shifted Vh to become more negative (from -60.6 +/- 2.1 to -63.1 +/- 1.8 mV). In the presence of flecainide, Vmax further decreased by 20.2 +/- 2.6%, and Vh shifted from -63.1 +/ 1.8 to -65.0 +/- 1.5 mV. Comparison with the control unstretched fibers showed that flecainide significantly decreased Vmax by 34.0 +/- 2.7%, reduced the resting membrane potential by 3 +/- 1 mV, decreased Eov by 4 +/- 1 mV, and shifted Vh from -60.6 +/- 2.1 to -65.0 +/- 1.5 mV, while the APD50 and ERP did not change. In conclusion, the reduction of Vmax in the presence of flecainide was much greater in the stretched atrial muscle fibers than in the unstretched fibers, because the Vmax-resting potential relationship was shifted towards more negative potentials by both flecainide and stretching. These results suggest that flecainide exerts a stronger antiarrhythmic action on stretched atrial muscle fibers than on normal fibers. PMID- 8364007 TI - ACE inhibitors. PMID- 8364008 TI - Verapamil prevents sudden death in patients with increased heart size after an acute myocardial infarction. PMID- 8364009 TI - Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. AB - Mild homocysteinemia occurs surprisingly often in patients with premature vascular disease. We studied the possible enzymatic sources of this mild hyperhomocysteinemia and the control of homocysteine levels in plasma by treatment of patients with the cofactors and cosubstrates of homocysteine catabolism. We assessed homocysteine metabolism in 131 patients who had premature disease in their coronary, peripheral, or cerebrovascular circulation by using a standard oral methionine-load test. Impaired homocysteine metabolism occurred in 28 patients. We assayed levels of the primary enzymes of homocysteine catabolism in cultured skin fibroblast extracts from 15 of these 28 patients. The patients' cystathionine beta-synthase levels (3.68 +/- 2.52 nmol/h per milligram of cell protein, mean +/- SD) were markedly depressed compared with those from 31 healthy adult control subjects (7.61 +/- 4.49, P < .001). The patients' levels of 5 methyltetrahydrofolate: homocysteine methyltransferase were normal. While betaine: homocysteine methyltransferase was not expressed in skin fibroblasts, 24 hour urinary betaine and N,N-dimethylglycine measurements were consistent with normal or enhanced remethylation of homocysteine by betaine: homocysteine methyltransferase in the 13 patients tested. When treated daily with choline and betaine, pyridoxine, or folic acid, there was a normalization of the postmethionine plasma homocysteine level in 16 of 19 patients. Our results indicate that mild homocysteinemia in premature vascular disease may be caused by either a folate deficiency or deficiencies in cystathionine beta-synthase activity. It does not necessarily involve deficiencies of either 5 methyltetrahydrofolate:homocysteine methyltransferase or betaine:homocysteine methyltransferase. Effective treatment regimens are also defined. PMID- 8364011 TI - In vitro large-wound re-endothelialization. Inhibition of centrosome redistribution by transient inhibition of transcription after wounding prevents rapid repair. AB - Rapid, efficient re-endothelialization of large wounds is characterized by a specific sequence of cytoskeletal events that occur after wounding. Wounds 1.5 mm wide were created down the middle of confluent porcine aortic endothelial monolayers to study regulation of repair. The wounded cultures were incubated for short periods with cycloheximide or actinomycin D to test the hypothesis that transient inhibition of translation and transcription at the time of wounding disrupts rapid repair by interfering with centrosome redistribution to the front of the cell, an early event associated with cell migration. Although centrosome reorientation did not occur when protein synthesis was inhibited with 20 micrograms/mL cycloheximide for 1 hour before and for up to 4 hours after wounding, reorientation did occur by 2 hours after cycloheximide was washed out. The times taken for the wound to close for cycloheximide-treated and control cells did not differ (60 +/- 1.1 vs 60 +/- 0.8 hours). When transcription was inhibited with 0.25 micrograms/mL actinomycin D for 1 hour before and for 1 hour after wounding, re-endothelialization was dramatically reduced. The time taken for the wound to close was almost five times longer (288 +/- 5.3 hours) than for control cells. The cells moved very slowly, maintaining a flattened, spread-out shape, as opposed to being elongated. The centrosomes did not reorient to the front of the cell throughout the entire period. However, addition of actinomycin D for 2 hours when centrosomes had already moved to the front of the cells (4 hours after wounding) did not reduce subsequent wound repair (60 +/- 1.3 hours). This study supports our hypothesis that centrosome redistribution is essential for efficient wound repair and suggests that redistribution is regulated by transcription of essential gene(s) that is induced immediately after wounding by an unknown short-lived signal. Two possible signals are the loss of cell contact and/or a soluble substance released from the cells at the time of wounding. When the signal is unable to induce transcription, dysfunctional repair occurs by a very slow centrosome-independent process. PMID- 8364010 TI - Concerted effects of lipoproteins and angiotensin II on signal transduction processes in vascular smooth muscle cells. AB - Low-density (LDL) and high-density (HDL3) lipoproteins dose-dependently activate phosphoinositide turnover and elevate cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured vascular smooth muscle cells (VSMCs) from either human (microarterioles and aorta) or rat (aorta) sources. High-performance liquid chromatography analysis of cell extracts revealed comparable spectra of inositol phosphate isomers generated in response to either LDL, HDL3, or angiotensin II (Ang II). Thus, lipoproteins and Ang II may use similar, if not identical, signal transduction pathways for the generation and metabolism of inositol phosphates and intracellular Ca2+ mobilization in VSMCs. When Ang II was added in combination with either LDL or HDL3, the phosphoinositide and [Ca2+]i responses of VSMCs were either equal to or even greater than the sum of the effects elicited by the agonists individually. This additivity/synergy between Ang II and the lipoproteins was not accompanied by alteration in the half-maximally effective dose requirements of VSMCs for either Ang II (approximately 2 nmol/L, with or without lipoproteins) or lipoproteins (approximately 50 micrograms/mL for LDL and HDL3, with or without Ang II). Neither short-term (up to 10 minutes) nor long-term (48 hours) exposure of VSMCs to lipoproteins caused desensitization of phospholipase C and intracellular Ca2+ mobilization responses to either Ang II or lipoproteins. Since constant exposure of VSMCs to lipoproteins is a physiological circumstance, and because elevation of [Ca2+]i and activation of phosphoinositide turnover are pivotal events for VSMC contraction and growth, we suggest that the low concentrations of lipoproteins in the vessel intima may play an important role in regulating the response of the vasculature to Ang II. PMID- 8364012 TI - Beta-VLDL in hepatic lipase deficiency induces apoE-mediated cholesterol ester accumulation in macrophages. AB - Hepatic lipase-deficient subjects in the Ontario kindred are compound heterozygotes for hepatic lipase mutations (Ser267-->Phe and Thr383-->Met). Cholesteryl ester-rich beta-very-low-density lipoprotein (beta-VLDL) accumulates in plasma and such subjects have premature atherosclerosis. To determine a possible mechanism, we hypothesized that hepatic lipase-deficient beta-VLDL, homozygous for apolipoprotein (apo) E3, would cause cholesteryl ester accumulation and foam cell formation in macrophages. beta-VLDL and pre-beta-VLDL were isolated by Pevikon electrophoresis and incubated with J774 macrophages, cells that do not secrete apoE. beta-VLDL increased cellular cholesteryl ester content 13-fold, whereas pre-beta-VLDL increased cholesteryl ester sevenfold. beta-VLDL increased acyl CoA:cholesterol acyltransferase activity fourfold (measured as [14C]oleate incorporation into cholesteryl ester). Preincubation of hepatic lipase-deficient beta-VLDL with the anti-apoE monoclonal antibody 1D7, which inhibits binding of apoE to low-density lipoprotein receptors, inhibited cellular cholesteryl ester accumulation by 75%, whereas the anti-apoB blocking monoclonal antibody 5E11 failed to inhibit cellular cholesteryl ester accumulation. In contrast to hepatic lipase deficiency, beta-VLDL from type III subjects (E2/E2) failed to increase cellular cholesteryl ester or acyl CoA:cholesterol acyltransferase more than 1.5-fold. Thus, hepatic lipase deficient beta-VLDL readily induces cholesteryl ester accumulation in J774 macrophages, a process mediated by functional apoE3. This may explain the premature atherosclerosis observed in this kindred. PMID- 8364013 TI - Natural history of aortic and coronary atherosclerotic lesions in youth. Findings from the PDAY Study. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. AB - Pathology laboratories in nine cooperating centers collected arteries from 1532 persons 15 through 34 years of age who died of external causes, principally homicides, accidents, and suicides. A central laboratory stained the arteries and evaluated the atherosclerotic lesions. All of the aortas and about half of the right coronary arteries in the youngest age group (15 through 19 years) had lesions. The mean percent intimal surface involved by lesions, in 5-year age groups, increased from 15 through 34 years. Raised lesions increased with age in extent and prevalence in the aorta and the right coronary artery. Black subjects had more extensive fatty streaks than white subjects in all three arterial segments. Young women had more extensive fatty streaks in the abdominal aorta; young men had more in the thoracic aorta. Male subjects had more extensive and a higher prevalence of raised lesions than did female subjects in the right coronary artery. White and black subjects did not differ significantly in the extent of raised lesions. Among the three arterial segments, the right coronary had the least percentage of intimal surface involved with all types of lesions but had the highest proportion of raised lesions among total lesions. These results confirm the origin of atherosclerosis in childhood and show that the prevalence and extent of fatty streaks and fibrous plaques increase rapidly during the 15- through 34-year age span. PMID- 8364014 TI - Familial HDL deficiency due to marked hypercatabolism of normal apoA-I. AB - In this article, we describe a 46-year-old man with severe high-density lipoprotein (HDL) deficiency and his kindred. In the proband, HDL cholesterol and apolipoprotein (apo) A-I levels were 5 and 4.5 mg/dL, respectively. Xanthomata, xanthelasma, arcus corneae, and hepatosplenomegaly were not present. The proband had coronary artery disease, but it was impossible to state whether the HDL deficiency cosegregated with premature coronary artery disease in this kindred. Pedigree analysis was suggestive of a codominant familial disease. Polymerase chain reaction amplification of the apoA-I gene of the proband, followed by subcloning and sequencing, did not reveal any mutation in either the coding regions or intron-exon junctions. A kinetic study using deuterated leucine to endogenously label apoA-I was performed to elucidate the metabolic basis of the apoA-I deficiency. We demonstrated marked hypercatabolism of apoA-I in the proband, with a fractional catabolic rate more than 10 times faster than normal; the plasma residence time of apoA-I in the proband was only 0.38 day compared with 4.10 days in a control subject. The apoA-I production rate was also substantially decreased in the proband. The association of a normal apoA-I gene sequence with marked hypercatabolism of apoA-I is similar to that described in Tangier disease. However, except for the presence of mild, diffuse, corneal deposits, this patient had no evidence of the reticuloendothelial cholesterol deposition characteristic of Tangier disease. This study establishes that a form of severe hypoalphalipoproteinemia distinct from Tangier disease can be caused by marked hypercatabolism of a normal A-I apolipoprotein. PMID- 8364015 TI - LDL inhibits the mediation of cholesterol efflux from macrophage foam cells by apoA-I-containing lipoproteins. A putative mechanism for foam cell formation. AB - Although the accumulation of cholesterol in macrophages appears to be an initial step in atherogenesis, low-density lipoprotein (LDL), a major risk factor for atherosclerosis, does not promote cholesterol accumulation in macrophages in its native form. On the other hand, apolipoprotein (apo) A-I-containing lipoprotein removes cholesterol from cholesterol-loaded macrophages (foam cells) and prevents cholesterol from accumulating in the cells. We examined the effect of LDL on cholesterol removal by two species of apoA-I-containing lipoproteins, one containing only apoA-I (LpA-I) and the other containing apoA-I and apoA-II (LpA I/A-II). When foam cells were incubated with LpA-I or LpA-I/A-II, cellular cholesterol mass was reduced. In contrast, when LDL was added, the cholesterol reducing capacities of these lipoproteins were dose-dependently inhibited by LDL. In the presence of LDL, LpA-I and LpA-I/A-II removed free cholesterol preferentially from LDL rather than from the plasma membrane of foam cells. In addition, a fair amount of cellular cholesterol was directly moved to LDL rather than to LpA-I or LpA-I/A-II. The cellular cholesterol that moved to LDL was completely compensated for by the cholesterol influx from LDL to foam cells. Thus, net cholesterol efflux (a combination of influx and efflux) from foam cells was inhibited by LDL. These results, taken together, indicate that LDL may accelerate foam cell formation by inhibiting cholesterol removal from the cells and that elevated levels of plasma LDL may become a risk factor for atherosclerosis by inhibiting the function of LpA-I and LpA-I/A-II at the cellular level. PMID- 8364016 TI - Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells. AB - Elevated blood levels of homocysteine represent an independent risk factor for premature arterial vascular disease and thrombosis. We investigated whether homocysteine could induce tissue factor (TF) procoagulant activity in cultured human endothelial cells. Homocysteine increased cellular TF activity in a time- and concentration-dependent manner. Low concentrations of homocysteine (0.1 to 0.6 mmol/L), similar to those found in the blood of patients with homocystinuria, enhanced TF activity by 25% to 100%. Other sulfur-containing amino acids (cystine, homocystine, cysteine, and methionine) induced less TF activity than did homocysteine; however, beta-mercaptoethanol and dithiothreitol were more effective than homocysteine in increasing TF activity. Preincubation of homocysteine with a sulfhydryl inhibitor such as N-ethylmaleimide prevented homocysteine induction of TF activity. A quantitative polymerase chain reaction method indicated that homocysteine increased TF mRNA in endothelial cells. These results indicate that an atherogenic amino acid, homocysteine, can initiate coagulation by the TF pathway through a mechanism involving the free thiol group of the amino acid and by TF gene transcription. These data support the hypothesis that perturbation of vascular coagulant mechanisms may contribute to the thrombotic tendency seen in patients with homocystinuria. PMID- 8364017 TI - Interaction of oxidized HDLs with J774-A1 macrophages causes intracellular accumulation of unesterified cholesterol. AB - Uptake of modified lipoproteins by resident arterial monocytes/macrophages is believed to be a key event in the formation of foam cells and thus in the early phases of atherosclerosis. Low-density lipoproteins (LDLs) that undergo oxidative changes become suitable for uptake by macrophages through a specific scavenger receptor that leads to cholesteryl ester accumulation. Because the interaction of other oxidized lipoproteins with macrophages has been poorly investigated, we studied the effect of oxidatively modified high-density lipoproteins (HDLs) on the sterol metabolism of J774-A1 macrophages. Unlike native HDLs, oxidized HDLs caused a concentration-dependent accumulation of unesterified cholesterol and decreased [14C]oleate incorporation into steryl esters. Oxidized HDLs also decreased [14C]acetate incorporation into newly synthesized sterols. Cell surface binding of 125I-oxidized HDLs to the macrophages was saturable, with an apparent dissociation constant (Kd) of 0.96 nmol/mL. Both oxidized and acetylated LDLs but not native lipoproteins could compete for binding of 125I-oxidized HDL. The data support the conclusion that the effects elicited by oxidized HDLs on the sterol metabolism of macrophages are significantly different from those of native HDLs. The binding of oxidized HDLs to macrophages occurs at sites that are likely the same as those for modified LDLs. We speculate that, if occurring in vivo, HDL oxidation would generate modified lipoproteins capable of modulating the cholesterol homeostasis of macrophages. PMID- 8364018 TI - Inhibition of thromboxane biosynthesis and platelet function by indobufen in type II diabetes mellitus. AB - Indobufen is a reversible inhibitor of platelet prostaglandin G/H-synthase. To verify the dose dependence of the antiplatelet effect of indobufen on ex vivo and in vivo indexes of thromboxane (TX) biosynthesis and TXA2-dependent platelet function, we studied nine patients with non-insulin-dependent diabetes mellitus (NIDDM). This was a randomized, double-blind, crossover study in which each patient was treated with three different daily regimens (50 mg BID, 100 mg BID, and 200 mg BID) of indobufen for 1 week, with a 7-day washout period between treatments. Urinary 11-dehydro-TXB2 excretion averaged 58.2 +/- 21.8 ng/h at baseline. TX metabolite excretion was reduced dose dependently by indobufen: by 67% at 50 mg BID, 72% at 100 mg BID, and 81% at 200 mg BID. Platelet cyclooxygenase activity, ATP release, collagen-induced platelet aggregation, and bleeding time also were modified dose dependently by indobufen. Biochemical demonstration of suppressed platelet TXA2 in vivo was accompanied by evidence of inhibited platelet function as assessed ex vivo. Under pathophysiological conditions, such as NIDDM, which are associated with enhanced TXA2 synthesis, more than 95% suppression of platelet cyclooxygenase activity may be necessary to produce virtually maximal inhibition of platelet TXA2 biosynthesis in vivo. PMID- 8364019 TI - Macrophage-conditioned medium and beta-VLDLs enhance cholesterol esterification in SMCs and HSFs by LDL receptor-mediated and other pathways. AB - Thioglycolate-elicited mouse peritoneal macrophages were incubated for 24 hours in serum-free Dulbecco-Vogt medium containing 0.5% fatty acid-poor bovine serum albumin. This conditioned medium, designated MP medium, was used for experiments with bovine aortic smooth muscle cells (SMCs) or human skin fibroblasts (HSFs). Dulbecco-Vogt medium of the same albumin content but without macrophages served as a control medium. In SMCs labeled from plating the [3H]cholesterol and incubated with hypercholesterolemic rabbit beta-very-low-density lipoprotein (beta-VLDL) in Dulbecco-Vogt medium for 24 hours, there was an increase in cellular [3H]cholesteryl ester (CE) content compared with cells incubated without lipoprotein. When MP medium was used for the incubation of SMCs with beta-VLDL, cellular [3H]cholesteryl ester content increased threefold compared with cells incubated with Dulbecco-Vogt medium. A smaller increase in cholesterol esterification in the presence of MP medium was also encountered with low-density lipoprotein (LDL). The MP medium-induced increase in [3H]cholesterol esterification was not evident up to 6 hours of incubation. Similar results were also obtained with HSFs. The increase in [3H]cholesterol esterification with MP medium in the presence of beta-VLDL was also elicited in cells obtained from LDL receptor-negative donors with familial hypercholesterolemia (FH-HSF), even though in these cells significantly less [3H]cholesteryl ester was formed in the presence of beta-VLDL. MP medium contains numerous agents that could be responsible for the increase in cellular [3H]cholesteryl ester induced by lipoproteins. The first considered was lipoprotein lipase, but lack of inhibition of the MP medium effect by antiserum to lipoprotein lipase did not support this possibility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364020 TI - Exercise training decreases plasma cholesteryl ester transfer protein. AB - To assess the effect of exercise on the plasma concentration of cholesterol ester transfer protein (CETP) and its possible influence in mediating the exercise associated redistribution of cholesterol among plasma lipoproteins, we measured plasma CETP in 57 healthy normolipidemic men and women before and after 9 to 12 months of exercise training. The training protocol resulted in significant changes in VO2max (mean +/- SD, +5.3 +/- 3.5 mL.kg-1 x min-1), body weight (-2.5 +/- 3.5 kg), plasma triglycerides (-25.7 +/- 36.3 mg/dL), high-density lipoprotein cholesterol (HDL-C) (+2.6 +/- 6.2 mg/dL), and ratios of total cholesterol to HDL-C (-0.30 +/- 0.52) and low-density lipoprotein cholesterol (LDL-C) to HDL-C (-0.18 +/- 0.45) (all P < or = .05) but no change in lipoprotein(a). CETP concentration (in milligrams per liter) fell significantly in response to training in both men (n = 28, 2.47 +/- 0.66 to 2.12 +/- 0.43; % delta = 14.2%; P < .005) and women (n = 29, 2.72 +/- 1.01 to 2.36 +/- 0.76; % delta = 13.2%; P < .047). The CETP change was observed both in subjects who lost weight (n = 28, delta mean weight = -5.0 kg; delta CETP = -0.42 +/- 0.79; % delta = 15.4%; P < .009) and in those who were weight stable (n = 29, delta mean weight = -0.12 kg; delta CETP = -0.29 +/- 0.78; % delta = 10.4%; P < .055).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364021 TI - Influx, efflux, and accumulation of LDL in normal arterial areas and atherosclerotic lesions of white Carneau pigeons with naturally occurring and cholesterol-aggravated aortic atherosclerosis. AB - This study investigated the hypothesis that increased influx of low-density lipoprotein (LDL) accounts for the natural development of atherosclerosis in a characteristic (susceptible) site in the distal thoracic aorta of White Carneau (WC) pigeons and the exacerbation of atherosclerosis by cholesterol feeding. The influence of dietary cholesterol-induced changes in LDL composition on LDL influx into the artery was also investigated. As a measure of the influx of LDL into the artery, we determined the arterial accumulation of radiolabeled LDL after 1 hour. Nine 50-month-old WC pigeons with naturally occurring atherosclerosis and seven 14-month-old WC pigeons with atherosclerosis accelerated by 10 months of cholesterol feeding were studied. In the absence of atherosclerotic lesions, we found no evidence for increased accumulation of LDL at the susceptible site. In fact, more LDL accumulated in less susceptible normal arterial areas near the heart (approximately 90 nl/h per square centimeter) than in the susceptible distal thoracic aorta (approximately 35 nl/h per square centimeter). In the absence of atherosclerotic lesions, LDL accumulation (nanoliters per hour per square centimeter) was not influenced by hypercholesterolemia, although mass transport of LDL cholesterol into the artery was increased. Naturally occurring atherosclerotic lesions accumulated five times as much LDL as the adjacent normal arterial area (P < .001), whereas cholesterol-aggravated atherosclerotic lesions in different arterial sites accumulated four to 26 times as much LDL as the adjacent normal artery (P < .05). Cholesterol-aggravated atherosclerotic lesions at the most susceptible site accumulated five times as much LDL as naturally occurring atherosclerotic lesions in the corresponding arterial site (823 +/- 241 vs 175 +/- 45 nl/h per square centimeter, mean +/- SEM; P < .005). Arterial accumulation of LDL was influenced very little by changes in LDL composition induced by cholesterol feeding. In another study with young WC pigeons free of atherosclerosis and other WC pigeons with cholesterol-aggravated atherosclerosis, we injected differently labeled LDL 0.5 and 1 hour before sacrifice to investigate whether efflux of LDL from the artery was significant during a 1-hour period of LDL uptake. Although efflux of LDL from all arterial sites occurred during 1 hour, differential efflux could not account for regional differences in 1-hour arterial LDL accumulation. This study suggests that the characteristic susceptibility of the distal thoracic aorta of WC pigeons to atherosclerosis and the exacerbation of atherosclerosis by cholesterol feeding cannot be explained by differences in influx or efflux of LDL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364022 TI - Abundant expression of apoprotein E by macrophages in human and rabbit atherosclerotic lesions. AB - Previous studies have demonstrated the presence of apoprotein (apo) E protein and message in arterial lesions. To determine the source of the synthesized apoE, we performed simultaneous in situ hybridization and immunocytochemistry on human and rabbit atherosclerotic tissue. Studies of serial sections of aortic atherosclerotic lesions from humans and hypercholesterolemic New Zealand White rabbits and Watanabe heritable hyperlipidemic rabbits revealed a similar pattern of macrophage-specific apoE expression in the rabbit and human lesions. In early lesions of rabbit atherosclerotic tissue, in which many macrophages were present, there was abundant expression of apoE mRNA. Northern blot analyses of total mRNA obtained from arterial macrophage-derived foam cells, freshly isolated from ballooned, cholesterol-fed New Zealand White rabbits, demonstrated positive hybridization with an apoE-specific riboprobe. Western blot analyses of conditioned media from the isolated foam cells placed in culture for up to 24 hours demonstrated the presence of secreted apoE. These studies demonstrated that in atherosclerotic lesions, arterial wall macrophages synthesize and secrete apoE and probably account for most of the apoE synthesized in the atherosclerotic artery. PMID- 8364023 TI - Effects of site-directed mutagenesis on the N-glycosylation sites of human lecithin:cholesterol acyltransferase. AB - There are four potential N-glycosylation site (Asn-X-Ser/Thr) in human lecithin:cholesterol acyltransferase (LCAT, residues 20, 84, 272, and 384). To study the role of the N-linked sugars, the codon for Asn at these positions was replaced with one for Thr (AAC to ACC). The wild-type and mutant LCAT cDNAs were used to transfect COS-6 cells from which RNA was isolated; cDNAs were synthesized by reverse transcription and subjected to the polymerase chain reaction, which showed that all transfectants synthesized LCAT-specific mRNA. No intracellular or secreted LCAT was detected with the Asn272-->Thr transfectants, indicating that this residue is essential for intracellular processing. All other single-point transfectants were secretion-competent. Although there was detectable LCAT protein inside the cells and in the media of the transfectant, Asn84-->Thr, its specific activity and secreted amount were only 26% and 58% of the wild type, respectively. This implies that Asn84 is critical for full activity but not for intracellular processing. The amount secreted, specific activity, and Vmax of LCAT (Asn20-->Thr) were similar to those of the wild-type LCAT. LCAT (Asn384- >Thr) differed from the wild-type LCAT only by a lower Km. These results suggest that glycosylation at residues 20 and 384 is not essential for intracellular processing, secretion, or activity. PMID- 8364024 TI - Structure of an interleukin-1 beta mutant with reduced bioactivity shows multiple subtle changes in conformation that affect protein-protein recognition. AB - Site-specific mutagenesis was used to obtain the human interleukin-1 beta mutant protein with glycine substituted for threonine at position 9 (IL-1 beta Thr9Gly). The mutant maintains receptor binding but exhibits significantly reduced biological activity. The crystal structure of IL-1 beta Thr9Gly has been determined at 2.4-A resolution by molecular replacement techniques and refined to a crystallographic R-factor of 19.0%. IL-1 beta Thr9Gly crystallizes in a different space group (P6(5)22) than does native IL-1 beta (P4(3)); thus the molecules pack differently. Their overall structure is similar, nevertheless, with both composed of 153 amino acids which form 12 antiparallel beta-strands. However, significant conformational differences both close to and far from the site of the mutation may explain the mutant's altered properties. PMID- 8364025 TI - Structural basis for transfer RNA aminoacylation by Escherichia coli glutaminyl tRNA synthetase. AB - The structure of Escherichia coli glutaminyl-tRNA synthetase complexed with tRNA2Gln and ATP refined at 2.5-A resolution reveals structural details of the catalytic center and allows description of the specific roles of individual amino acid residues in substrate binding and catalysis. The reactive moieties of the ATP and tRNA substrates are positioned within hydrogen-bonding distance of each other. Model-building has been used to position the glutamine substrate in an adjacent cavity with its reactive carboxylate adjacent to the alpha-phosphate of ATP; the interactions of the carboxyamide side chain suggest a structural rationale for the way in which the enzyme discriminates against glutamate. The binding site for a manganese ion has also been identified bridging the beta- and gamma-phosphates of the ATP. The well-known HIGH and KMSKS sequence motifs interact directly with each other as well as with the ATP, providing a structural rationale for their simultaneous conservation in all class I synthetases. The KMSKS loop adopts a well-ordered and catalytically productive conformation as a consequence of interactions made with the proximal beta-barrel domain. While there are no protein side chains near the reaction site that might function in acid-base catalysis, the side chains of two residues, His43 and Lys270, are positioned to assist in stabilizing the expected pentacovalent intermediate at the alpha-phosphate. Transfer of glutamine to the 3'-terminal tRNA ribose may well proceed by intramolecular catalysis involving proton abstraction by a phosphate oxygen atom of glutaminyl adenylate. Catalytic competence of the crystalline enzyme is directly shown by its ability to hydrolyze ATP and release pyrophosphate when crystals of the ternary complex are soaked in mother liquor containing glutamine. PMID- 8364026 TI - Crystal structure determination and refinement at 2.3-A resolution of the lentil lectin. AB - We report on the X-ray structure determination of the orthorhombic crystal form of lentil lectin by molecular replacement using the pea lectin coordinates as a starting model. The structure was refined at 2.3-A resolution with a combination of molecular dynamics refinement and classical restrained least-squares refinement. The final R value for all data Fo > 1 sigma (Fo) between 7.0- and 2.3 A resolution is 0.164%, and deviations from ideal bond distances are 0.014 A. The C-terminus of the beta-chain proved to be 23 amino acids longer than found in previous studies. This together with several inconsistencies between the previously determined amino acid sequence and the observed electron density forced a redetermination of the amino acid sequence of the protein. The overall structure is very similar to that of pea lectin and isolectin I of Lathyrus ochrus, the most prominent deviations being confined to loop regions and the regions of intermolecular contact. The largest difference between the pea and lentil lectin monomers is situated in the loop region of amino acids 73-79 of the beta chain. There are no significant differences between the two crystallographic independent lentil lectin monomers in the asymmetric unit. The model includes 104 well-defined water molecules, of which a significant number have a counterpart in the pea lectin structure. As for the other legume lectins, each lentil lectin monomer contains one calcium ion in a highly conserved environment. On the contrary, the manganese binding sites are distorted with respect to the pea lectin and concanavalin A structures. The Asp beta 121 side chain apparently does not ligate the Mn2+ ion. This difference is consistent in both lentil lectin monomers and agrees with earlier solution studies. Possible implications for oligosaccharide binding are discussed. PMID- 8364027 TI - Oxygen equilibrium properties of asymmetric nickel(II)-iron(II) hybrid hemoglobin. AB - Asymmetric Ni(II)-Fe(II) hybrid hemoglobin, XL[alpha(Fe)beta(Fe)][alpha(Ni)beta(Ni)], in which the alpha 1 beta 1 dimer containing ferrous protoporphyrin IX and the complementary alpha 2 beta 2 dimer containing Ni(II) protoporphyrin IX were cross-linked between Lys-82 beta 1 and Lys-82 beta 2 by reaction with bis(3,5-dibromosalicyl) fumarate, was synthesized and characterized. We have previously shown that (i) Ni(II) protoporphyrin IX, which binds neither oxygen nor carbon monoxide, mimics a fixed deoxyheme with respect to its effect on the oxygen equilibrium properties of the counterpart iron subunits in both symmetric Ni(II)-Fe(II) hybrid Hbs [Shibayama, N., Morimoto, H., & Miyazaki, G. (1986) J. Mol. Biol. 192, 323-329] and (ii) the cross-linking used in this study little affects the oxygen equilibrium properties of hemoglobin [Shibayama, N., Imai, K., Hirata, H., Hiraiwa, H., Morimoto, H., & Saigo, S. (1991) Biochemistry 30, 8158-8165]. These remarkable features of our model allowed us to measure the oxygen equilibrium curves for the first two steps of oxygen binding to the alpha 1 beta 1 dimer within the hemoglobin tetramer. At all pH values examined, the affinities of this asymmetric hybrid for the first oxygen molecule are as low as those of native hemoglobin. The hybrid did not show cooperative oxygen binding at pH 6.4, while significant cooperativity was observed with rising pH; i.e., the Hill coefficient was increased from 1.41 to 1.53 upon a pH change from 7.4 to 8.4. The electronic absorption spectrum of Ni(II) protoporphyrin IX in the alpha 2 subunit was changed upon carbon monoxide (or oxygen) binding to the alpha 1 beta 1 dimer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364028 TI - Disulfide bond assignments and secondary structure analysis of human and murine interleukin 10. AB - Interleukin 10 (IL-10), which was first discovered by its ability to inhibit the synthesis of various cytokines, most notably gamma interferon, from Th1 helper cells, displays pleiotropic immunoregulatory properties. Human and murine IL-10 have a high amino acid sequence identity (ca. 73%) which includes the conservation of all four cysteine residues in human IL-10 and the first four out of five cysteine residues for murine IL-10. Chemical analysis was used to determine that both recombinant human and recombinant murine IL-10 contain two disulfide bonds. The disulfide pairs for each were determined by mass spectrometric and reversed-phase HPLC analysis of trypsin-derived polypeptide fragments. The disulfide bond assignments for both species were similar in that the first cysteine residue in the sequence paired with the third and the second paired with the fourth. The fifth cysteine in murine IL-10 was determined by chemical modification to be unpaired. Far-UV circular dichroism analysis indicated that the secondary structure of recombinant human and murine IL-10 are composed of ca. 60% alpha-helix. Reduction of the disulfide bonds structurally destabilized the protein and led to a structure containing only 53% alpha-helix. The reduced protein displayed no in vitro biological activity in a mast cell proliferation assay. These studies indicate that IL-10 is a highly alpha-helical protein containing two disulfide bonds, either one or both of which are critical for its structure and function. In addition, these properties suggest that this interesting cytokine may belong to the alpha helical cytokine class of hematopoietic ligands. PMID- 8364029 TI - Dimerization and tetramerization properties of the C-terminal region of chromogranin A: a thermodynamic analysis. AB - Chromogranin A, which is a high-capacity, low-affinity Ca2+ binding protein, has recently been shown to exist in monomer-dimer and in monomer-tetramer equilibria at pH 7.5 and 5.5, respectively [Yoo, S. H., & Lewis, M. S. (1992) J. Biol. Chem. 267, 11236-11241]. The pH appeared to be a necessary and sufficient factor determining the types of oligomer formed. In the present study, using 14 synthetic peptides representing various portions of chromogranin A, we have identified a region in chromogranin A which exhibited dimerization and tetramerization properties at pH 7.5 and 5.5, respectively. Of the 14 peptides, only the conserved C-terminal region (residues 407-431), represented by peptide 14, showed the oligomerization property, existing in a dimeric state at pH 7.5 and in a tetrameric state at pH 5.5. The delta G degrees values of tetramerization were approximately -18.0 kcal/mol, and the delta G degrees value of dimerization was -4.6 kcal/mol. Although peptide 14 represented only 6% of the entire sequence, the delta G degrees value of -18.0 kcal/mol accounted for 80-83% of the delta G degrees values (-21.6 to -22.7 kcal/mol) of tetramerization of intact chromogranin A. Unlike the tetramerization mechanisms of intact chromogranin A where the presence of 35 mM Ca2+ changed the tetramerization mechanism from an enthalpically driven to an entropically driven reaction, the tetramerization mechanism of peptide 14 remained entropically driven regardless of the presence of Ca2+. Likewise, dimerization of the peptide was also entropically driven.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364030 TI - Purification and biochemical characterization of tubulin from the budding yeast Saccharomyces cerevisiae. AB - We describe a method for isolating milligram quantities of assembly-competent tubulin from the budding yeast Saccharomyces cerevisiae. The tubulin is > 95% purified and free of contaminating enzyme activities. As a result, it has been possible to determine the yeast tubulin equilibrium-binding constant for Mg-GTP and the tubulin GTPase activity under nonassembling and assembling conditions. We also determined the critical concentration for yeast tubulin polymerization and found it to be significantly lower than that for bovine brain tubulin under identical conditions. Similarly, the dynamic properties both of individual yeast microtubules and of bulk microtubule suspensions were significantly different from those of bovine brain microtubules free of microtubule-associated proteins. The data suggest that the properties of the yeast tubulin may reflect the particular functional requirements of the yeast cell. With this method, it is now possible to introduce any desired tubulin gene mutation into the budding yeast and correlate the phenotypic effects of the mutation in cells with the effects of the mutation on the biochemical and polymerization properties of the tubulin. PMID- 8364031 TI - Phage display and selection of a site-directed randomized single-chain antibody Fv fragment for its affinity improvement. AB - The affinity of an antibody Fv fragment was improved by semirational design involving site-directed randomization and phage display. On the basis of the predicted model of an anti-2-phenyloxazol-5-one (phOx) antibody Fv fragment, into which the ligand was inserted with the help of nuclear Overhauser enhancement (NOE) data, residues close to the hapten were identified. Seven of these residues in the third hypervariable regions of light and heavy chains were randomized in polymerase chain reactions (PCR) using degenerate oligonucleotides. Resulting clones were expressed as single-chain Fv (scFV) fragments on the surface of filamentous phage and selected for binding to phOx-conjugated bovine serum albumin. Selected Fv fragments were analyzed for hapten affinity by fluorescence quenching, and several mutants with improved affinities were identified. Phage selection on the basis of binding was very successful when phage scFv mutants differed in affinity by at least a factor of 6. Smaller differences did not result in predominant selection of the best binder. Combination of the two point mutations most crucial for improved hapten binding decreased the dissociation constant of the Fv for phOx 11-14-fold. Hapten binding of the improved Fv was analyzed in NOE experiments. PMID- 8364032 TI - Apocytochrome P450cam is a native protein with some intermediate-like properties. AB - Holo- and apocytochrome P450cam were studied by differential scanning calorimetry (DSC), limited proteolysis, second-derivative spectroscopy, circular dichroism, and size-exclusion chromatography. The holoprotein shows three folding units (domains) in DSC. The prosthetic group is related to the most unstable domain, which has a thermal transition at 41.9 degrees C. Compared with the holoprotein, apocytochrome P450cam has a reduced helix content. The protein is compact as judged by the Stokes radius and is still able to undergo a two-state transition. However, the enthalpy change at thermal melting is reduced from 980 kJ/mol for the holoprotein to 135 kJ/mol for the apo form. Parts of the molecule have a destabilized tertiary structure. This is indicated by second-derivative spectroscopy, circular dichroism in the near-ultraviolet region, and a high susceptibility to proteolytic digestion. Apocytochrome P450cam is considered a native protein with the extremely low stability of delta G = 7.5 kJ/mol, thus showing at the same time intermediate-like properties. The importance of the properties for in vivo folding are discussed. PMID- 8364033 TI - Cytochrome P450 4A4: expression in Escherichia coli, purification, and characterization of catalytic properties. AB - Rabbit lung prostaglandin omega-hydroxylase (P450 4A4) was expressed in Escherichia coli using the isopropyl beta-D-thiogalactopyranoside (IPTG) inducible expression vector pCWori+, containing the full-length cDNA encoding the P450 4A4. The first seven codons were changed to reflect E. coli codon bias [a modification of the method of Barnes et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 5597-5601]; only the second residue of P450 4A4 was altered (Ser to Ala), while the remaining mutations were silent. This strategy was adopted in order to minimize changes in the structure of the expressed enzyme. Induction by IPTG of the apoprotein peaked after 6 h, and by including the heme precursor delta aminolevulinic acid, enzymatic activity peaked 12 h after addition of IPTG. The isolated membrane fraction, free of cell debris, contained 12-15 nmol of P450/L of media. The expressed enzyme was purified to electrophoretic homogeneity, and kinetic and spectrophotometric data indicate that this expressed, purified enzyme is equivalent to the enzyme purified from rabbit lung. The Km for PGE1 was determined to be 3.0 microM, which is the same as that obtained for the enzyme purified from lung [Williams et al. (1984) J. Biol. Chem. 259, 14600-14608]. The CO-reduced difference spectrum of purified P450 4A4 exhibited a lambda max at 450 nm, and the absolute absorbance spectrum of the pyridine hemochromogen revealed a typical b type heme. To characterize P450 4A4 further, the catalytic activities with prostaglandin E1 (PGE1), arachidonate, 15-hydroxyeicosatetraenoic acid (15 HETE), and palmitate were investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364034 TI - Critical assessment of the presence of an NADPH binding site on neutrophil cytochrome b558 by photoaffinity and immunochemical labeling. AB - The presumed NADPH dehydrogenase function of the heterodimeric cytochrome b558 in the neutrophil oxidase complex has been investigated by combined photoaffinity labeling and immunoblot analysis of membrane proteins from bovine neutrophils. The photoaffinity probe was a radiolabeled analog of NADPH, [4-[N-(4-azido-2 nitrophenyl)[3H]amino]butyryl]NADPH ([3H]azido-NADPH), and the antibodies were directed against the C-terminal regions of the two subunits of cytochrome b558. Plasma membrane vesicles obtained by differential centrifugation of bovine neutrophil homogenates were routinely used as a source of NADPH oxidase. They were permeabilized by sodium deoxycholate to facilitate the access of NADPH or its azido analog to the totality of the specific binding sites. In the absence of light, azido-NADPH behaved as a competitive inhibitor of NADPH oxidase with a Ki of 6 microM, and was able to bind to high-affinity specific binding sites with a Kd of 5-6 microM, indicating a higher affinity of the oxidase for the photoprobe than for the substrate NADPH (KM = 30-40 microM). Upon photolabeling, the oxidase was fully inactivated. Following resolution of the membrane proteins by SDS-PAGE, a predominant photolabeled protein band of 80-100 kDa was revealed, which coincided with the large subunit (beta) of cytochrome b558 identified by immunoblot in a parallel gel. The enzymatic deglycosylation of photolabeled neutrophil membranes shifted the masses of both the photolabeled band and the immunoreactive beta subunit from 80-100 to 55-65 kDa in accordance with the glycoprotein nature of the beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364035 TI - Inhibition of scavenger receptor-mediated modified low-density lipoprotein endocytosis in cultured bovine aortic endothelial cells by the glycoprotein processing inhibitor castanospermine. AB - Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizidine) is a plant alkaloid that inhibits alpha-glucosidases, including the glycoprotein processing glucosidase I. When endothelial cells were grown for 48 h, or longer, in the presence of this alkaloid, they produced scavenger receptors for modified low density lipoproteins (LDL) that had mostly Glc3Man7-9(GlcNAc)2 structures rather than the usual complex types of oligosaccharides. Furthermore, growth in the presence of castanospermine resulted in a substantial inhibition in degradation of endocytosed 125I-acetylated LDL, as well as a dose-dependent inhibition of 125I-acetylated LDL binding to these cells. Scatchard analysis of binding curves indicated that the diminished binding was due to a decrease in the number of scavenger receptor molecules at the cell surface rather than to a change in the affinity of the receptors for their ligand. Since castanospermine-treated cells had the same total number of cellular receptor molecules as did controls cells, it seemed likely that castanospermine caused an alteration in receptor targeting, rather than an inhibition in receptor synthesis or a stimulation in receptor degradation. Density gradient fractionation of cell homogenates showed that castanospermine-treated cells did have a much greater percentage of scavenger LDL receptor molecules in the endoplasmic reticulum-Golgi fraction and fewer receptors in the plasma membrane fraction, whereas normal cells showed the opposite distribution. PMID- 8364036 TI - Actin-binding peptide from smooth muscle myosin light chain kinase. AB - The objective of this study was to localize the actin-binding site in the smooth muscle myosin light chain kinase. Limited proteolysis by thermolysin indicated that hydrolysis of the kinase at the N-terminal end of the molecule resulted in loss of actin-binding ability. Various methods of cleavage were investigated for the generation of a discrete actin-binding peptide. The method chosen was cleavage at the cysteine residues by the 5,5'-dithiobis(2-nitrobenzoic acid) cyanide complex. This procedure yielded an actin-binding peptide of approximate M(r) 17,000. The peptide was purified and shown to possess the actin-binding properties of the native myosin light chain kinase. The binding constant of the isolated peptide and parent enzyme to actin was estimated as 7.5 x 10(4) M-1. From the amino acid composition of the peptide and comparison with the sequence of gizzard myosin light chain kinase, it was suggested that the actin-binding site is located within the N-terminal sequence 1-114. Comparison with other actin binding proteins shows some similarities to gizzard alpha-actinin and caldesmon. PMID- 8364037 TI - Crystallographic analysis of C-C-A-A-G-C-T-T-G-G and its implications for bending in B-DNA. AB - Stacked B-DNA double helices of sequence C-C-A-A-G-C-T-T-G-G exhibit the same 23 degrees bend at -T-G-G C-C-A- across the nonbonded junction between helices that is observed in the middle of the decamer helix of sequence C-A-T-G-G-C-C-A-T-G, even though the space group (hexagonal vs orthorhombic), crystal packing, and connectedness at the center of the bent segment are quite different. An identical bend occurs across the interhelix junction of every monoclinic crystal structure of sequence C-C-A-x-x-x-x-T-G-G, suggesting that T-G-G-C-C-A constitutes a natural bending element in B-DNA. The bend occurs by rolling stacked base pairs about their long axes; there is no "tilt" component. Of the three possible models for A-tract bending--bent-A-tract, junction bends, or bent-non-A--which cannot be distinguished by solution measurements, all crystallographic evidence over the past 10 years unanimously supports the non-A regions as the actual bending loci. PMID- 8364038 TI - Pit-1/GHF-1 binds to TRH-sensitive regions of the rat thyrotropin beta gene. AB - Three regions within the 5'-flanking region of the TSH beta gene have A-T-rich sequences which have sequence similarity to binding sites for the pituitary specific POU domain transcription factor Pit-1/GHF-1. These three regions have been termed TSH A (-274 to -258 bp), TSH B (-336 to -326 bp), and TSH C (-402 to 384 bp). TSH A and TSH C are able to confer 2-6-fold TRH stimulation to the heterologous viral thymidine kinase (tk) promoter in transient expression assays in GH3 pituitary cells; TSH C can confer a 3-10-fold increase in basal enhancer activity as well. TSH A, B, and C DNAs all bound Pit-1 from GH3 cell nuclear extracts, based on gel mobility shift analysis in which antibody against Pit-1 prevented the formation of specific DNA-GH3 nuclear protein complexes. TSH A and TSH C also each formed several additional DNA-nuclear protein complexes which were not observed with TSH B. Some of these complexes may contain Pit-1 as their formation was inhibited by the addition of Pit-1 antibody; other complexes, however, were not altered by antibody treatment. All three A-T-rich elements bound in vitro translated Pit-1, with calculated affinities of 360 (A), 125 (B), and 38 (C) nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364039 TI - Ribonucleoprotein particle assembly and modification of U2 small nuclear RNA containing 5-fluorouridine. AB - An in vitro assembly/modification system was used to study the effect of 5 fluorouridine (5-FU) incorporation on the biosynthesis of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Labeled U2 RNAs were transcribed in vitro with 5-fluoro-UTP either partially supplementing or completely replacing UTP during synthesis. The resulting U2 RNAs have levels of 5-fluorouridine that range from 0 to 100% of the uridine content. When incubated in reactions containing extracts from HeLa cells, these 5-FU U2 RNAs are assembled into RNPs that are recognized by anti-Sm monoclonal antibody even when there is a complete replacement of uridine with 5-FU. However, when the in vitro assembled U2 snRNPs are subjected to buoyant density gradient centrifugation, the particles that contain 100% 5-FU are not resistant to salt dissociation. When the in vitro assembled U2 snRNPs were analyzed by velocity sedimentation gradient centrifugation, 5-FU incorporation correlated with a shift in the sedimentation rate of the particles. With 100% 5-FU incorporation, the peak of radioactivity shifted to approximately 15 S (control U2 RNA was at approximately 12 S). This peak from 5-FU U2 snRNPs was not resistant to dissociation on cesium sulfate gradients. The amount of pseudouridine (psi) found in the RNA from snRNP assembled in vitro on control and 5-FU-containing U2 RNAs was determined, and even at very low levels of 5-FU incorporation (5% replacement), the formation of psi was severely inhibited (36% of control). At higher levels of 5-FU incorporation, there was essentially no psi formed. PMID- 8364040 TI - Perturbation of the carboxy terminus of HIV-1 Rev affects multimerization on the Rev responsive element. AB - Perturbations within the transactivation and carboxy-terminal domains of HIV-1 Rev were examined for effects on Rev responsive element (RRE) binding activities in vitro and biological activity in vivo. Binding affinities, specificities, and multimerization of the transactivation mutants M10 and Rev/Rex M10-16 on the RRE were equivalent to wild-type Rev. Substitution of the Rex transactivation domain within Rev resulted in the incorporation of an internal methionine residue which, when cleaved with CNBr and subsequently purified, produced a protein species (CNBr-Rev) unable to fully multimerize on the RRE. Instead, two discrete protein dependent species were generated in the gel shift assay. Furthermore, CNBr-Rev was observed to bind to the RRE with high specificity and an equilibrium binding constant of 6 x 10(-10) M. A C-terminal Rev deletion mutant (Rev M9 delta 14) lacking amino acids 68-112 displayed identical RRE binding characteristics to the CNBr-Rev protein. This protein, which lacks both the activation and the C terminal domains, was biologically inactive but maintained the ability to discriminate the RRE from nonspecific RNA. Deletion of amino acids 92-112 resulted in a Rev mutant (Rev M11 delta 14) which bound to the RRE with wild-type affinity and high specificity. This purified mutant was observed to be aberrant in multimerization activity on the RRE with reduced multimerization apparent in the gel shift assay. However, Rev M11 delta 14 possessed biological activity equivalent to wild-type Rev in a cell-based p24 ELISA assay. These results suggest that polymerization on the RRE is dispensable for Rev activity and that two monomeric Rev proteins bound to the RRE are sufficient for biological activity. Furthermore, in vivo experiments using the Rev/Rex chimeric mutant and the M10 transdominant mutant as well as in vitro dissociation rate studies with Rev M11 delta 14 and Rev M9 delta 14 suggest that the M9 through M11 domain of the protein may be involved in RRE-dependent specific Rev dimerization. PMID- 8364042 TI - Mechanism of inhibition of human leucocyte elastase by monocyclic beta-lactams. AB - The kinetic and catalytic mechanisms of time-dependent inhibition of human polymorphonuclear leukocyte elastase (HLE) by the monocyclic beta-lactams described by Knight et al. [Knight, W.B., et al. (1992) Biochemistry 31, 8160] are investigated in this work. The dependence of the pseudo-first-order rate constant (k(obs)) on inhibitor concentration was saturable. The individual kinetic constants for the inhibition by L-680,833, [S-(R*,S*)]-4-[(1-(((1-(4- methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-4-oxo-2- azetidinyl)oxy]benzeneacetic acid, and L-683,845, [S-(R*,S*)]-4-[(1-(((1-(5 benzofuranyl)butyl)amino)carbonyl)- 3,3-diethyl-4-oxo-2 azetidinyl)oxy]benzeneacetic acid, at pH 7.5 were k(inact) = 0.08 and 0.06 s-1 and Ki = 0.14 and 0.06 microM, respectively. The relative potency of this class of compounds as measured by k(inact)/Ki is primarily controlled by the Ki, term which ranged from 6 nM to 8 mM, while K(inact) was relatively insensitive to structural changes and varied by only an order of magnitude. Inactivation by the beta-lactams was efficient, requiring only 1.3 and 1.7 equiv of L-680,833 and L 683,845 to inactivate HLE. These values are indicative of some partitioning between turnover of inhibitor and inactivation. The partition ratio ranged as high as 3.5:1 depending upon the structure of the inhibitors, but this ratio was essentially independent of the availability and identity of a leaving group at C 4 of the lactam ring. Inactivation and partitioning liberate the leaving group when present at C-4. p-Hydroxy-m-nitrophenylacetic acid is liberated from this position at a rate similar to that for enzyme inactivation, suggesting kinetic competence of this process. Other products observed during the interaction of L 680,833 with HLE include a substituted urea, a species previously observed during the base-catalyzed decomposition of this class of compounds, and small amounts of products observed during reactivation of beta-lactam-derived HLE-I complexes. Both the pH dependence of k(inact)/Ki for the inactivation of HLE by [S-(R*,S*)] 4-[(1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-diethyl - 4-oxo-2 azetidinyl)oxyl]benzoic acid and V/K for HLE-catalyzed substrate hydrolysis indicate that a single ionizable group with a pK of approximately 7 must be deprotonated for both processes. This group is likely the active site histidine. The data are consistent with initial formation of a Michaelis complex, acylation of the catalytic serine, and loss of the leaving group at C-4 of the original beta-lactam ring followed by partitioning between regeneration of active enzyme and production of a stable enzyme-inhibitor complex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364041 TI - Thermodynamic and kinetic studies of DNA triplex formation of an oligohomopyrimidine and a matched duplex by filter binding assay. AB - The filter binding method was found to be a powerful method for studying the formation of triplexes composed of a single-stranded homopyrimidine and a duplex with a matched purine-pyrimidine tract. With this technique, we were able to determine thermodynamic and kinetic parameters for triplex formation between a homopyrimidine 19-mer (5'-TCCTCTTCTTTTCTTTCTT-3') and a duplex with sequence 5' GCAGGAGAAGAAAAGAAAGAACG-3' for the purine strand. The experiments were performed over a wide pH range (3.8-7.4) and a temperature range of 0-35 degrees C. pH and temperature dependencies of the thermodynamic parameters were best explained in terms of a three-state model for triplex formation at low temperatures relative to the melting point. The main results were as follows: (1) pH dependence of the dissociation constants of the triplex is a result of the rapid acid-base equilibrium of pyrimidine single strands; (2) the association rate for triplex formation decreases with increasing pH in accordance with the dissociation constants; (3) the dissociation constant is virtually temperature-independent at low pH, while it becomes strongly temperature-dependent with increasing pH (these results can be explained in terms of a negative, non-zero delta Cp for triplex formation at low pH); (4) the association rate decreases with increasing temperature, and the resulting negative activation energy indicates that the triplex formation process involves a quasi-stable intermediate; (5) the triplex formation is a second-order reaction at low pH, whereas it can be interpreted as a third-order reaction at neutral pH, suggesting that different triplex formation pathways are observed depending on the pH. PMID- 8364044 TI - Recombinant expression and partial characterization of the human formyl peptide receptor. AB - FMLP-receptor DNA was expressed in Escherichia coli. The expressed product could specifically bind FMLP. This is the first-reported expression of a functional FMLP receptor in Escherichia coli. We confirm that receptor glycosylation is not essential for ligand binding. A deletion mutant did not bind FMLP, suggesting that the deleted portion plays a role in ligand binding. PMID- 8364045 TI - [Radiology of stroke]. AB - Today radiologic methods play an important role in the diagnosis of cerebral stroke. The aim of the radiologist, however, should not only be to classify the stroke into the four main categories (ischemic stroke, intracerebral bleeding, subarachnoid hemorrhage, sinovenous thrombosis), but also to interpret the findings with regard to the etiology of the disease. The pattern of lesions gives information about the etiology of ischemic stroke; the correct interpretation of these lesion patterns allows one to optimize therapeutic decisions. This paper additionally focuses on the differential diagnosis of intracerebral hemorrhage and the CT and MR signs of sinovenous thrombosis. New developed concepts in the field of stroke therapy and prophylaxis call for authority and continuous education of the radiologist on this topic. Pure descriptions of radiologic findings without an understanding of the pathogenesis of the disease will be ignored by the clinician. On the other hand, the radiologist can turn the therapeutic decisions in the right direction by combining morphological descriptions with pathogenetic orientated interpretations. In this way, the radiologist can contribute to the reduction of costs in the public health system. PMID- 8364043 TI - Mitogenic action of osteogenic growth peptide (OGP): role of amino and carboxy terminal regions and charge. AB - We have recently reported the discovery of a 14-amino-acid osteogenic growth peptide (OGP). In vivo OGP increases bone formation and trabecular bone density. Physiologically it is found in serum complexed to an OGP binding protein (OGPBP). In vitro OGP has a biphasic effect on osteoblastic MC 3T3 E1 and fibroblastic NIH 3T3 cell proliferation; at low concentrations (0.01-1.0 and 1.0-100.0 pM, respectively) it is highly stimulatory with an inhibition at higher doses. To assess possibilities of labeling synthetic OGP to obtain radio- or fluorescent ligands, OGP analogues were extended at the N- or C-termini with Cys or Cys(S NEtSucc) or the OGP Tyr-10 replaced by 3-I(Tyr). All analogues with N-terminal modifications, as well as the [Cys15]OGP-NH2 retained the OGP-like dose-dependent effect on proliferation of the MC 3T3 E1 and NIH 3T3 cells, although the magnitude of stimulation was lower, approx. 2/3 that of the native-like synthetic OGP. The [Cys15(S-NEtSucc)]OGP-NH2 and [3-I(Tyr10)]OGP shared only the inhibitory activity of OGP. This suppression is further shared by a number of other positively and negatively net charged, but not net neutral, peptides. Both N terminal-modified analogues displayed a decreased binding activity to the OGPBP. All analogues except reverse OGP, [3-I(Tyr10)]OGP and [Cys15(S-NEtSucc)]OGP-NH2 reacted with anti-OGP antibodies. These data are not only important for labeling purposes but suggest a respective role for the OGP N-and C-terminal regions in binding to the OGPBP and putative OGP receptor. It appears that the OGP proliferative activity represents the net effect of stimulation specific to the OGP structure and nonspecific inhibition associated with the peptide's high positive net charge. PMID- 8364046 TI - [Quality criteria of DSA in neurologic problems]. AB - The further development of quality assurance in radiology requires also criteria for more complex examinations like digital subtraction angiography (DSA). The physical condition of the patient and his cooperation, the knowledge and experience of the physician, as well as the technical parameters of the DSA-unit, and the technique of examination determine the quality of any angiography. Aspects of these factors are discussed. It is found that, especially for neuroradiologic studies, the complex problem of quality can only be solved in part by measurable parameters. Only the performance of the DSA-system can be defined by measurements. Other factors defining quality cannot be measured at least to the same degree. The most relevant criteria of quality, however, are: have there been complications and can the clinical question be answered adequately by the DSA-study. PMID- 8364047 TI - [Signal to noise ratio or the number of perceptible gray tones in the x-ray picture. I. The dependence on the system sensitivity S (DIN 6867)]. AB - It is shown that the number of contrasts which can be differentiated on a radiograph depends on the detail size, the noise, and the viewing conditions. The minimum signal-to-noise ratio (SNR) for a perception approach is equivalently described by the SGA value. This testing method was first developed by De Belder and Bollen to examine the visibility of low contrast details. The correlation between the SGA and the speed class S of the system can be explained by this method. PMID- 8364048 TI - [Feasibility of the differential diagnostic imaging of neck lymphomas]. AB - In 51 patients with cervical swellings, pretherapeutic examinations by ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) were carried out for the confirmation of exclusion of cervical lymph node metastases. By use of the M/Q ratio and morphological criteria, it is possible with ultrasound to differentiate between relatively enlarged lymph modes and lymph node metastasis with a certainly of > 90%. This was only possible in CT after administration of contrast media and the success rate was lower (72%). Both by use of the M/Q ratio and contrast medium administration, MRI is able to distinguish between lymph node metastases and reactively altered lymph nodes. Differentiation between Hodgkin/non-Hodgkin lymphomas of the neck and reactively enlarged lymph nodes is also possible with the aid of the M/Q ratio. In such cases, sonography and MRI are superior to CT. A certain differentiation between lymph node metastases and Hodgkin/non-Hodgkin lymphomas is only possible in some cases. However, there are indicative criteria for differential diagnosis. A delineation between specific lymph node inflammations and glomus carotid tumors is also possible because of the differing take-up of contrast medium in CT and MRI and via doppler sonographic criteria. PMID- 8364049 TI - [Different evaluations of the staging of Hodgkin's and non-Hodgkin's lymphomas (NHL) with computer tomography and lymphography by different observers]. AB - In this report, the differences in the evaluation of CT and lymphography findings by different observers is discussed. The study included 132 men and 79 women (146 NHL and 65 Hodgkin lymphomas). A total of 185 CT examinations and 78 lymphographies were available for reevaluation. In the lymphographies, discongruent findings were reported twice as frequently as in the CT scans (15% and 9%). An optimized examination protocol for CT and consistent criteria for the interpretation of lymphographic findings could possible lead to a better diagnostic evaluation. PMID- 8364050 TI - [The thoracic radiologic significance of the width of the azygous vein and its correlation with right atrial blood pressure]. AB - The widths of the azygos vein were measured in 150 patients and correlated with the pressure in the right heart-atrium. We found a significant logarithmic correlation (r = 0.8) between the two parameters. Radiologic measurement of the width of V. azygos in chest radiographs or CT is useful to evaluate the function of the right heart. PMID- 8364051 TI - [Change in radiation exposure in x-ray diagnosis today?]. AB - The dosage for the single exposure is today from a half to a quarter of the dosage used 20 years ago. The number of diagnostic X-ray examinations performed has increased; this increase concerns mainly patients whose life expectancy is shorter than the latency period to the manifestation of an X-ray induced malignoma and whose reproduction probability is very low. The genetic risk therefore is zero. This was demonstrated for coronary angiography. The dose distribution in the body shows important differences between conventional X-ray diagnostic and computed tomography. One cannot calculate the radiation risk of roentgen diagnostics from a dose applied to the population or from a dose per head of a population. Such a dose is not suitable for comparison with radiation exposure due to natural sources and civilization. The overall risk of disease is not altered by radiation exposure of an adequate roentgen diagnosis method. PMID- 8364052 TI - [Sonographic demonstration and guided fine needle biopsy of subcutaneous lipomas]. AB - Lipomas are common soft tissue tumours. Patients are sometimes referred to ultrasound examinations because of diagnostic problems. Nine cases of cytologically or histologically verified subcutaneous lipomas are presented focusing on their sonographic appearances and on the fine-needle biopsy technique. PMID- 8364053 TI - [Contrast medium nephropathy--a contribution to the reduction of examination risks]. AB - The radiologist is rarely directly confronted with contrast medium-induced renal impairment or even renal failure. In contrast to allergic side effects, the disorders do not become apparent until a few days after the investigation. The relevance of "contrast-medium nephropathy" should not, however, be underestimated: prior contrast medium injections are the initial cause of at least 10% of all cases of acute renal failure. The risk associated with such an investigation can be reduced if the risk factors are known, the patient receives an affective premedication in preparation for the investigation, and if preference is given to non-ionic contrast media. PMID- 8364054 TI - [Typical nuclear spin tomographic intensity distribution patterns in different knee joint diseases using a gradient echo sequence]. AB - The knee joints of 31 patients and 3 volunteers were examined with a 1.5 T Magnetom using 3D-gradient echo sequences. We measured for the most widespread diseases: the gonarthrosis (n = 23) and rheumatoid arthritis (n = 8) the signal intensities in all joint parts and the typical signal plots were worked out. In case of minimal changes at the articular cartilage, the method developed and tried out by us can facilitate diagnosis. A special aspect of this method is also the patient follow-up which is now possible quantitatively and objectively. PMID- 8364055 TI - [Wrong diagnosis of a foreign body incorporation after a dog bite in the hand]. AB - The case of a patient with foreign body incorporation after a dog bite is reported. The radiographic aspect and the density in CT was that of a fragmented tooth. The particle was visible in plain radiography. After operative extraction, the patient was discharged without any symptoms. PMID- 8364056 TI - [Nuclear spin tomographic findings in compensated chronic hemolysis. A case report of a hereditary spherocytosis]. AB - A case report of a 58-year-old patient with hereditary spherocytosis and large paravertebral masses in the thorax and abdomen is presented MRI detects the origin of the masses with typical signal intensities of the masses and the bone marrow in T1 and T2 weighted sequences as extramedullary hematopoiesis. In this special case there is bleeding into these masses and, as often, liver hemosiderosis and splenomegaly. PMID- 8364057 TI - [MR tomography and MR angiography of an extensive glomus jugulare tumor]. AB - The diagnosis of a glomus jugulare tumour was established by MR tomography and MR angiography. MR tomography demarcated the tumour from the surrounding tissue and MR angiography showed the vascularity of the glomus tumour. PMID- 8364058 TI - [Magnetic resonance tomography in heart septal defects. Model studies on parameter optimizing]. AB - Various flow phenomena can occur in MR tomography of the heart. In the present study the influence of various examination parameters on the imaging of flow phenomena behind cardiac septum defects was investigated by means of a model. In the examination by fast field echo sequence (FFE) the contrast between poststenotic jet and surrounding area was most pronounced if short echo times (TE 10 ms), a narrow flip angle (d = 10 degrees) and layers of minor thickness (d = 5 mm) had been selected. The number of acquisitions and the flow compensation exercised only slight influence on contrast. Our results point to the possibility of obtaining quantitative information on cardiac septum defects if the influence of examination parameters on the imaging of flow phenomena is accurately known. PMID- 8364059 TI - [Serotonin as a photoprotector of the oxygen-transporting function of hemoglobin]. AB - Oxygen-binding properties of human hemoglobin modified by UV-light (240-400 nm) in dose range (1.51 + 6.04) x 10(2) J/m2 together with serotonin (10(-4) M) has been studied by means of spectrophotometry. UV-radiation results in increase of the oxygen affinity of hemoglobin. Serotonin displays the photoprotective effect on the hemoglobin oxygen-transport function. Mechanisms of photoprotection of the biogenic amine are proposed for discussion. PMID- 8364060 TI - [Salt-induced critical type phase transition in a water-protein matrix of serum albumin molecules]. AB - Effective thermodynamic parameters of activation of label transition between two microsurroundings in water-protein matrix (WPM) of spin-labelled molecules of serum albumin (HSA-SL) in 0.001 M phosphate buffer, pH 7.3 within concentration range of NaCl (m3) (10(-3) M to 2 M and concentration range of protein (m2) 50 to 200 mg/ml were determined. The phase transition (PT) between two structures of water in WPM is revealed within the m3 range 0.01 M to 0.1 M. It is close to the type I PT and more expressed at high protein concentrations. As m3 increases (to 0.2 M when m2 = 50 mg/ml and to 0.7 when m2 = 200 mg/ml) PT-I is transformed into PT of the critical type. This is indicated to zero values of the higher order derivatives of Gibbs energy of activation with respect to salt concentration, as well as by the maximum values of positive disjoining pressure in these points. The biological significance of this phenomenon is discussed. PMID- 8364062 TI - [The effect of point amino acid substitutions on the stability of phage T4 lysozyme. I. Asn101---Asp substitution]. AB - The amino acid replacement Asn101-->Asp in the T4 phage lysozyme was obtained by site-directed mutagenesis and the plasmid mutant protein expression was constructed. Though the mutant protein circular dichroism (CD) spectrum is virtually unchanged as compared with the wild type protein and the enzymatic activity is 90% of that of the wild type protein, the stability of this mutant to urea-induced unfolding decreases and two stages in the denaturation process are observed. PMID- 8364061 TI - [Temperature causes structural and functional changes in lactate dehydrogenase from fish skeletal muscles]. AB - Adaptation of fishes to low and high environmental temperatures gives rise to certain changes in kinetic and structural properties of LDH from skeletal muscles. The KM versus temperature plot for pyruvate of the enzyme isolated from fishes adapted to low temperatures has a minimum at low measurement temperatures, whereas adaptation to high temperatures leads to the enzyme showing a minimum at high temperatures. The LDH isolated from fishes adapted to low environmental temperatures is more stable relative to both thermal and urea-induced inactivation. The differences in the kinetic properties of the enzymes from fishes adapted to low and high temperatures disappear after treatment with urea and subsequent reactivation. PMID- 8364063 TI - [The effect of point amino acid substitutions on T4 phage lysozyme stability. II. Transition of a protein molecule to the "molten globule" state with replacements Asp10---His, Asn101---Asp, Arg148---Ser]. AB - The amino acid replacements (Asp10-->His, Asn101-->Asp, Arg148-->Ser) in the T4 phage lysozyme were obtained by site directed mutagenesis and the plasmid for mutant protein expression was constructed. At acid pH (pH 2.7) the mutant is in the conformational state with properties of the molten globule (Ptitsyn, 1992): 1) the mutant protein molecule is essentially compact, 2) its circular dichroism (CD) spectrum in the near ultra violet (UV) region is drastically reduced in intensity as compared with the wild type protein spectrum, 3) the CD spectrum in the far UV region indicates the presence of a pronounced secondary structure in the mutant, 4) unlike the wild type protein, the mutant protein can bind the hydrophobic fluorescent probe ANS. PMID- 8364064 TI - [The effect of fixed water molecules on fractal properties of globular protein surfaces]. AB - On the base of the technique developed by the authors together with Schmidt the fractal properties of the 17 globular proteins have been analysed using the crystal structure data at high resolution. For all the proteins there are the coordinates of fixed water molecules in the protein data bank. For each protein the fractal dimension of its surface D has been calculated with and without taking into account the fixed water molecules located inside a 3-Angstrom hydrated layer. Small but systematic decrease of the DS values for the proteins with the fixed water molecules has been demonstrated. It means that the fixed water molecules tend to fill gaps on the protein surfaces and in that way to smooth the surfaces. The volumes and the molecular surfaces of the proteins have been also calculated on the base of the cube technique. The molecular surfaces of the proteins with the fixed water molecules prove to decrease. This fact can be considered as the indirect evidence that the protein surfaces become to be smoother. PMID- 8364065 TI - [IR-spectroscopic study of the interaction of chromium salts with native DNA]. AB - Infrared spectra of some unoriented films of DNA contained CrCl3, K2Cr2O7 and Cr2(SO4)3 have been obtained at relative humidities (r.h.) 0 to 93%. Chromium cations were shown to interact with phosphoric groups of DNA molecules. Cr2(SO4)3 or K2Cr2O7 content exceeds 0.1 Cr/P, the sugar-phosphate backbone of the double helix becomes irregular and nucleic bases unstacked, i.e. denaturation of DNA occurs. A very small amount of the salt, less than 0.01 Cr/P contained in DNA films prevents the conformational transition of the double helix from the B to A form induced by r.h. decreasing. The efficiency of the chromium salts in preventing the transition falls in the row: Cr2(SO4)3 > K2Cr2O7-CrCl3. PMID- 8364066 TI - [Prevention of binding of Nile red with hydrophobic proteins and surface cuvettes using detergents]. AB - The nile red fluorescence in solutions containing Triton X-100, human serum albumin and hexadecane in different combinations was investigated. The dye fluorescence in phosphate buffer after 2-4 min incubation strongly decreased because of the dye aggregation and was stable in a detergent solution. The intensity of nile red fluorescence in the detergent solution was not changed after the addition of equal weight concentration of albumin and increased more than 2 times after the addition of the same concentration of hexadecane. The detergent eliminated the nile red sorption by cuvette surface. It is concluded that the detergent addition increases nile red selectivity as a lipid probe in the lipid-protein systems. PMID- 8364067 TI - [Conformational mechanism for transforming energy during active ion transport in a biological membrane]. AB - A statistical model of active transport of ions in the biomembrane is presented. The coefficient of energy conversion for linear and non-linear processes in this system is obtained. It is shown that in the linear case this coefficient is equal to that obtained in linear thermodynamics. On the basis of the maximum of this coefficient transport parameters for ions are found. The results of the statistical model are in a good agreement with the experiments on the biological membranes. PMID- 8364068 TI - [Model of the response of the membrane transport system to an alternating electric field]. AB - We suggest a mathematical model of the transmembrane ionic transport system, which can produce the damped concentration oscillations. The influence of the periodic electric field is considered under assumption, that the ionic fluxes near the membrane depend on the medium potential. The estimated resonance frequency for the K(+)-H+ antiport system in bilayer membrane is less than 1 Hz. PMID- 8364069 TI - [Change in the permeability of liposome phospholipid membranes under the effect of Bacillus thuringiensis delta-endotoxins]. AB - We studied release of the fluorescent calcein marker from egg-lecithin liposomes under action of intact delta-endotoxin from Bacillus thuringiensis var. israilensis, and hydrolysed preparation of delta-endotoxin from Bacillus thuringiensis var. kurstaki together with the motional parameters of 5- and 12 doxyl stearic radical probes in the liposomal membrane. The yield of the non penetrating fluorescent marker was shown to be a sensitive indicator of the disturbance of the membrane barrier function. PMID- 8364070 TI - [H+-K+-exchange and formation of H2 in E. coli mutants with defects in the H+ ATPase complex and potassium transport]. AB - It was shown that 2H(+)-K(+)-exchange through H(+)-K(+)-pump composed of H(+) ATPase complex F0F1 and Trk-system of potassium accumulation, H(+)-K(+)-exchange through H(+)-K(+)-antiport, composed of H(+)-channel F0 and of system with Trk defect, and H2-production in E. coli grown in anaerobic conditions, change in mutants with defects of F0F1 and potassium transport. In unc-mutant of E. coli AN 936 with defects of c-subunit F0 (M(r) 8,4 kDa) H(+)-K(+)-exchange and H2 production disappeared. Mutants of E. coli TK 509 (2240) with defect of Trk system not able to perform 2H(+)-K(+)-exchange, performed, however H(+)-K(+) exchange and H2-production which can be blocked of N, N'-dicyclohexylcarbodiimide (DCCD). In mutant of E. coli Tk 509 (2242) with defects of KdpA-protein of Kdp system of potassium accumulation, Trk A and Trk D proteins of corresponding systems of potassium accumulation, the H(+)-K(+)-exchange disappeared, while H(+) formation and H2-production, blocked by DCCD, external osmotic pressure and absence of potassium in the medium, persisted. It is assumed that 2H(+)-K(+) exchange, H(+)-K(+)-exchange and H2-production are connected, and the membrane bound format-hydrogenlyase oxidizing format to H2 and CO2, directly take part in interaction with F0F1 and Trk, as well as F0 and defective Trk-system in formation of supercomplexs. It is assumed that the format-hydrogen-lyase can interact with F0F1 without the Trk-system. PMID- 8364071 TI - [The effect of pyrazole on the conformational state of cell membrane phospholipids]. AB - A change of conformation of phospholipids in the presence of pyrazole was studied by the method of 1H-NMR spectroscopy with the use of hydrophilic paramagnetic probes Pr3+. It was shown that the ratio of transformation of the polar groups of the bilayer surface of sonicated phosphatidyl-choline increased in the presence of pyrazole as compared to the experimental values of the induced pseudocontact shifts of the phosphorylcholine groups. It was established that the earlier discovered complexes of pyrazole-phospholipids in the inert solution exhibited in the water phase. PMID- 8364072 TI - [The effect of nonequibrilium states of membrane-area electrolyte during dilution of cell suspensions]. AB - The flow rate distribution in the diluted suspension of human red blood cells was measured across the long rectangular capillary. The calculated rate distribution of Pousaseil's flow was shown to be spoiled, if the substances influencing the red blood cell aggregation were added to the suspension. The Pousaseil's flow rate distribution takes place under the same conditions which support the sedimentation rate distribution predicted for the small particles without interaction. The sedimentation and flow anomalies are suggested to arise from the simultaneous lateral media flow along the cell surface and ion transfer across the cell membrane. PMID- 8364073 TI - [Effect of radiation on the structural state of erythrocyte membranes]. AB - Using fluorescent probe 4-(n-dimethyl-aminostyryl)-1-methyl-pyridine (DSM) the effect of electrons with the energy 5 MeV on the structure of erythrocyte membrane has been investigated. It was found that in the irradiated erythrocyte ghosts the number of DSM binding sites increases. Irradiation was suggested to increase the negative surface charge of the erythrocyte membrane. PMID- 8364074 TI - [The role of photomodification, prevented by lipid peroxidation inhibitors, in the therapeutic effect of UV-irradiated blood in peritonitis in rats]. AB - The blood of healthy animals was irradiated at 254 nm with incident dose 0.05 Einstein/m2 and was thirdly infused to the rats in volume 2 ml/Kg body weight. The infusion of irradiated blood decreased the lethality of rats. Maximal therapeutic action was observed at 7-9th day after peritonitis induction. This effect was completely inhibited by injection the cyclooxygenase inhibitors aspirin or indomethacin (but not lipid antioxidants BHT or alpha-tocopherol) into irradiated portion of blood before irradiation. The therapeutic effect of irradiated blood is due to cyclooxygenase activation by UV-radiation. PMID- 8364075 TI - [Features of walking kinematics in early human development]. AB - Kinematic regularities between independent principal parameters of baby's (8-9 months age) walking were analysed. For the initial period of walking with support two characteristic properties were revealed: the duration of step cycle was close to constant and the structure of cycle--relation between duration of the swing and support phases was constant as well. Due to these properties a child's walking is different from the adult's one characterized by decrement duration of the cycle and an increase of the cycle structure with an increase of walking speed. The principles of neurophysiological model of generator which provides initial primitive organization and the following complication of kinematic program of walking are discussed. PMID- 8364076 TI - ["Tendon" action of two-joint muscles during human locomotion: transfer of mechanical energy between links in shock-absorbing and push-off phases]. AB - We hale evaluated experimentally the amounts of the mechanical energy transferred by the two-joint muscles between the links of legs during squat vertical jumps and landings after jumping down from a height of 0.5. The experiments have been conducted on file healthy subjects in the course of locomotions. The coordinates of markers attached to the subjects' bodies and the ground reaction forces have been registered. The energy transferred by the two-joint muscles from and to the links forming each joint has been determined by integration of the difference between the power developed in the joint by the control moment and the total power of the muscles serving the given joint. It has been shown, that at squat vertical jump (the push-off phase) the two-joint muscles transfer mechanical energy from the proximal links of the leg to the distal ones: from pelvis to shank (by the rectus femoris m.), and from thigh to foot (by the gastrocnemius m.). At landing (the shock-absorbing phase) the two-joint muscles transfer energy from the distal to proximal links: from foot to thigh (by the gastrocnemius m.), and from shank to pelvis (by the rectus femoris m.). Thus the one-joint muscles of the proximal links compensate for the deficiency in the force developed by the one-joint muscles of the distal links due to the "tendon action" of the two-joint muscles. During push-off, the muscles of the proximal links contribute to increase in the energy of the distal links, and in the shock-absorbing phase, to its dissipation. PMID- 8364078 TI - Febrile neutropenia. AB - Severe neutropenia and its related infectious complications remain a permanent threat for patients receiving intensive chemotherapy, especially in the context of bone marrow transplantation. Chemoprophylaxis and use of colony-stimulating factors have altered the severity of the clinical picture in a favorable direction: neutropenia can be shortened, and gram-negative infection can be made less frequent; neither can be yet abolished. Early therapy, eg, empiric combination treatment, remains the cornerstone of our approach to febrile neutropenia; the actual choice of agents is probably less important and should be guided by local epidemiologic conditions. The concepts of empiric therapy also starts to be more widely accepted for the control of fungal and viral infections. Finally, it is fair to recognize that, at the other end of the spectrum of febrile neutropenia, conventional chemotherapy that results in only moderate and short neutropenia can usually be managed without much problem, namely with broad spectrum monotherapy. Other possible simplified approaches should be investigated under controlled conditions and in patients selected on the basis of favorable prognostic factors. PMID- 8364079 TI - Clinical approaches to nutritional support in cancer. AB - Anorexia and weight loss are frequent complications of cancer and AIDS. Assessment of dietary records and nutritional requirements in patients with decreased food intake and weight loss will assist the dietitian, nurse, or physician in initially addressing the problem. Patients may respond well to nutritional counseling and food supplements, but persistent severe anorexia is common. Various pharmacologic strategies to reverse anorexia and weight loss have been tested, including corticosteroids, anabolic steroids, cyproheptadine, hydrazine sulfate, dronabinol, and megestrol acetate. Dronabinol was recently found to improve appetite in AIDS patients. Megestrol acetate is so far the only agent associated with improvements in appetite and weight in patients with cancer and AIDS. Enteral and parenteral nutrition may be helpful in selected patients with gastrointestinal obstruction or dysfunction, but it is not generally indicated in patients with end-stage disease. PMID- 8364077 TI - [Collective properties of the mutual-learned neuronal net systems in the information field]. AB - Model of neural networks system, in which networks interact by transmission and associative recognition of signals, is studied by computer simulation and qualitative approach. System behavior depends on the value of learning parameter epsilon, which determines the weight of writing in memory of each network every transmissible signal. Two different regimes are found: regime of auto-governed behavior, which depends only on initial networks characteristics, and regime of collective recognition of initial signal in form of a certain stable signals cycle. Analogy of this model and Aigen's hypercycle, the problem of creation of some new information in this model are discussed, too. PMID- 8364080 TI - Paraendocrine syndromes. AB - Paraendocrine syndromes are the remote effects of cancer that result from ectopic hormonal production. Recent investigations have concentrated in five areas that include the evaluation of diagnostic studies, the recognition of rare cases, the contribution of secondary hormones, the clinical distinctions of ectopic syndromes from endocrine disorders, and the efficacy of pharmaceutical agents in correcting hormonally induced biochemical imbalances. The three most common paraendocrine syndromes (humoral hypercalcemia of malignancy, the syndrome of inappropriate antidiuretic hormone production, and ectopic Cushing's syndrome) are the subject of this review. PMID- 8364081 TI - Unproven methods in cancer treatment. AB - The nature-based and nontoxic image makes application of unproven methods in oncology attractive in contrast to application of a mechanized scientific medicine. The application frequency of these treatments ranges from 10% to greater than 60%. Increasingly, the promoters try to create a scientific impression through a pseudologic cancer theory, a harmless diagnostic test, and a holistic treatment of every cancer. Of the big variety of unproven methods, which are summarized in 11 groups in this review, the following are discussed: anthroposophic and other mistletoe preparations; homeopathy; Maharishi Ayur-Veda; unproven anticancer diets; orthomolecular medicine, including ascorbic acid; and methods supposedly stimulating unspecific and specific defense mechanisms. In conclusion, physicians should beware of and have knowledge of currently used unproven cancer treatments for epidemiologic, social, economic, and scientific reasons. PMID- 8364082 TI - Cytogenetics and experimental models of sarcomas. AB - The sarcomas are an extremely heterogeneous group of neoplasms that continue to present substantial diagnostic and therapeutic challenges. It is notable, therefore, that great strides have been made in the genetic characterization of sarcomas over the past few years. The very consistent chromosome translocations in Ewing's sarcoma, myxoid liposarcoma, and alveolar rhabdomyosarcoma have been cloned, and the oncogenes deregulated by these translocations have been identified. These characteristic genetic aberrations can now be used as diagnostic markers. PMID- 8364083 TI - Osteosarcoma. AB - Findings from molecular genetic and cytogenetic investigations suggest that mutations in suppressor genes play a key role in osteosarcoma pathogenesis. RB and p53 are frequently involved and are speculated to be indispensable components. Alterations in putative suppressor genes on chromosomes 18q and 3q additionally may be involved in various patterns. The high resolution of magnetic resonance imaging in osteosarcoma imaging is confirmed, and the validity of dynamic gadolinium-enhanced imaging for estimation of tumor response is stated. The efficacy of single-drug high-dose methotrexate convincingly is shown to be 19%. Phase II trials with nonspecific immunostimulation using a synthetic liposomal mycobacterium-derived antigen (liposomal muramyl tripeptide phosphatidylethanolamine) do not yet allow us to draw conclusions on eventual efficacy. A novel and promising approach may be intervention in the endocrine or orthocrine and paracrine tumor growth regulation. Hypophysectomy in mice dramatically reduced plasma or insulin-like growth factor and local as well as systemic growth of transplanted osteosarcoma. The close interrelation between tumor response, surgical margins, and local control is demonstrated, as well as the fatal prognosis after local failure. Also, the validity of known risk factors in patients undergoing intensive chemotherapy has been confirmed. Interestingly, dose intensity was not found to influence prognosis. PMID- 8364084 TI - Rhabdomyosarcomas and other soft tissue sarcomas in pediatric patients. AB - Current therapy for childhood sarcomas, particularly rhabdomyosarcomas, is a multidisciplinary effort requiring input from various specialists. Significant progress has been made in lower-stage disease because of advances in chemotherapy, radiotherapy, and surgery, but cure rates remain poor in high-stage lesions, and there is significant morbidity after treatment of lesions with a favorable outcome. Histologic classification is not always predictive of behavior, but recent modifications promise better prognostic significance. Great advances have also been made in our understanding of the biology of these lesions; these advances offer the promise of future therapeutic applicability. Detection of genetic alterations in predisposed individuals is possible but raises several significant nontherapeutic issues. PMID- 8364085 TI - Soft tissue sarcoma in adults. AB - Over the past year, improved delineation of prognostic factors and other aspects of staging of localized sarcomas have been reported. Although little progress has been made in terms of improvement in adjuvant therapy, new efforts to enhance therapy for advanced disease, particularly through use of dose-intensive chemotherapy regimens with colony-stimulating factor support, have resulted in improved response rates and may herald the development of new chemotherapy regimens, which may be employed in future randomized studies in the early disease setting. PMID- 8364086 TI - The Lynch syndromes. AB - The Lynch syndromes, also referred to as hereditary nonpolyposis colorectal cancer, are reviewed, with particular attention given to their natural history, diagnosis, surveillance, and management. Lynch syndrome I is characterized by an autosomal dominantly inherited predisposition to early onset colorectal cancer, with proximal predominance and an excess of synchronous and metachronous colorectal cancers. Lynch syndrome II manifests all of the features of Lynch syndrome I but, in addition, shows an integral association with extracolonic cancers, particularly carcinomas of the endometrium and the ovary. There are no premonitory physical signs or biomarkers of genotypic risk. Therefore, the natural history features of the Lynch syndromes are crucial to their surveillance and management. PMID- 8364087 TI - New imaging techniques in gastrointestinal cancer. AB - Impressive advances in both anatomic and functional imaging of gastrointestinal tumors have been made in recent years, with several interesting studies appearing this past year. Increasingly, different imaging modalities have been used in combination and have shown complementation and improved accuracy. Improvements in detecting and defining local versus extended sites of cancer in various gastrointestinal organs have been made by conventional methods and by newer functional tests, including positron-emission tomography, receptor scintigraphy, and radioimmunodetection. With the US Food and Drug Administration approval of the first antibody-based cancer imaging agent, a new class of biologic imaging agents is coming of age in oncology and will likely experience the most use in management of colorectal cancer, permitting improved staging and disclosure of occult disease. In addition to gamma camera imaging, these radioactive biologic targeting agents hold promise for positron-emission tomography scanning and for cancer radioimmunotherapy. PMID- 8364088 TI - New surgical approaches to gastrointestinal cancer. AB - The outlook for patients with gastrointestinal malignancies has not altered appreciably over the past three decades. Surgery offers the only possibility of cure; it is important that, as less-invasive techniques are introduced, survival is not compromised. Most patients will have occult disseminated disease at presentation, and it is therefore important to evaluate adjuvant therapies. Regional therapy offers considerable potential for patients with advanced or recurrent disease. Better surgery, better staging, more appropriate surgery, the use of adjuvant therapy, and new approaches to the problem of advanced disease are likely to result in the reduction of mortality over the next decade. The surgical oncologist has an important role in defining optimum treatment of individual patients and in evaluating new therapies. PMID- 8364091 TI - Sarcomas. PMID- 8364090 TI - Supportive care. PMID- 8364089 TI - Combined modality treatment of gastrointestinal cancer. AB - During the past year, little of finite value has been published to change the approach to combined treatment modalities for the patient with gastrointestinal cancer. The value of adding other modalities to surgery to improve the cure rate has been marginal. Neoadjuvant and adjuvant treatment appear to be making inroads into the treatment of esophagus cancer, and newer development of less toxic treatment offers promise for the future. In stomach cancer, combined modality treatment is only of value for patients with locally advanced disease. In the United States, adjuvant chemotherapy is accepted as being of value for patients with colon cancer, and adjuvant treatment with both radiotherapy and chemotherapy is considered to be best for patients with surgically treatable rectum cancer. Primary liver cancer continues to offer a challenge for combined modality treatment, but a call for prospective, randomized control trials seems to be in order. PMID- 8364092 TI - Gastrointestinal tract. PMID- 8364093 TI - Conformational studies of hairpin sequences from the ColE1 cruciform. AB - Inverted repeat sequences derived from the ColE1 cruciform were investigated by nuclear magnetic resonance (NMR) and UV spectroscopy. It was shown that 15 different sequences exist as stable hairpin structures over a range of buffer conditions and DNA concentrations. Experiments with six oligomers (1-6) containing the native stem sequence and five base loops, found that the two hairpins with the wild-type loops (1-2) served as upper and lower bounds for the thermodynamic stability of all the other sequences. NMR experiments, including rotational correlation time measurements and NOESY spectra, were then performed on 1, the most stable hairpin sequence to begin to uncover a structural basis of its stability. PMID- 8364094 TI - Affinity labeling of bovine brain protein kinase C by tosyl lysyl chloromethane. A kinetic study. AB - The kinetics of inactivation of bovine brain protein kinase C (PKC) by N alpha-p tosyl L-lysyl chloromethane (TosLysCH2Cl) were investigated. In absence of activators PKC gave non-linear semilog inactivation plots. At each reagent concentration a plateau of residual activity was reached after some time; its value was inversely proportional to TosLysCH2Cl concentration but the plateau was not due to inactivator depletion. On the other hand, in the presence of Ca2+, phosphatidylserine and phorbol 12-myristate 13-acetate, the activity loss followed saturation kinetics, with k(inact) = 0.6 x 10(-3) s-1 and Kinact = 1.9 mM. The study of protection effects by ATP Mg2+ and histone required the presence of 50% glycerol in the incubation mixtures, otherwise the controls (kinase in the presence of activators and ATP Mg2+ or histone) rapidly lost activity. In the presence of 50% glycerol, the inactivation parameters were somewhat altered (k(inact) = 0.3 x 10(-3) s-1 and K(inact) = 0.2 mM); ATP Mg2+ proved to afford a mixed competitive-non competitive protection effect, while histone protected in a competitive manner with a Kp of 0.06 microgram/ml. In the presence and the absence of glycerol, plots of log k(obs) versus log inactivator concentration yielded straight lines with slopes of 0.7-0.9, indicating that 1 mol of reagent is sufficient for inactivation. The results described in this paper suggest that the reagent TosLysCH2Cl hits the catalytic domain of activated PKC at the active site, which is not available in resting PKC; in non-activated PKC, the labeling site would be different. PMID- 8364095 TI - Colicin A lysis protein promotes extracellular release of active human growth hormone accumulated in Escherichia coli cytoplasm. AB - The colicin A lysis protein (Cal) was used to direct the extracellular release of recombinant proteins produced in Escherichia coli. The cal gene, under the control of its inducible promoter, was introduced into an expression vector encoding the human growth hormone devoid of its signal sequence (Met-hGH). Cal and Met-hGH were simultaneously expressed at two different levels of Met-hGH induction. The results indicate that Cal causes the excretion of non-aggregated Met-hGH from the cytoplasm to the culture medium and that the Met-hGH is correctly folded since the released Met-hGH is antigenically indistinguishable from the authentic mature hGH and is biologically active in binding to specific receptor sites. PMID- 8364096 TI - An attempt to substitute the cell binding domain of human fibronectin in lambda phage J protein: computer design and expression. AB - We superimposed hydropathic indexes of the human fibronectin cell binding domain (CBD) on the lambda phage J protein by computer, and substituted 22 amino acids from the fibronectin CBD for a part of the lambda phage J protein. The fibronectin cell binding domain -Arg-Gly-Asp-Ser- (-RGDS-) localizes at the junction of hydrophobicity and hydrophilicity. We selected a similar hydrophobic to-hydrophilic junction in the J protein region for substitution. This junction corresponds to 150 bp of the PstI fragment of J protein cDNA. We synthesized 150 bp of the relevant PstI fragment that includes the cell binding domain region. The region was then constructed by serial cloning as an expression vector, pJCBD. The vector pJCBD expressed the fused protein named JCBD (M(r) 32 kDa) in E coli XL1-BLUE. The expressed JCBD protein was identified by Western blot analysis in the extract of the pJCBD carrying bacterial lysate using both rabbit anti-lambda phage antiserum and anti-CBD of fibronectin antibody. The JCBD protein appeared to recognize retinoblast cell membrane RGDS-directed receptors, detected by enzyme-linked immuno-sorbent assay and also by binding competition assay with synthetic pentapeptides, Gly-Arg-Gly-Asp-Ser (GRGDS) and Gly-Arg-Gly-Glu-Ser (GRGES). The former competitor inhibited completely fibronectin CBD-dependent binding activity of JCBD, the latter had no inhibitory activity. These results suggest that certain functional proteins engineered by computer design between human fibronectin cell binding domain and lambda phage J protein can be produced. PMID- 8364097 TI - Properties of Barrier, a novel Saccharomyces cerevisiae acid protease. AB - We have studied the specificity of Barrier, a protease secreted by Saccharomyces cerevisiae, towards its natural substrate alpha-factor, a tridecapeptide mating pheromone. Sub-fragments of alpha-factor synthesized or prepared by cyanogen bromide cleavage and a related pheromone from Saccharomyces kluveri were studied as potential substrates or competitive inhibitors. None of the tested peptides was a potent inhibitor or substrate for Barrier. Barrier shares extensive sequence similarity to the active site residues of aspartyl proteases but universal irreversible inhibitors of this class of enzymes failed to inactivate Barrier, suggesting that it is a novel fungal aspartyl protease. PMID- 8364098 TI - The rne gene and ribonuclease E. AB - The cloned rne+ gene complements temperature sensitive RNase E mutations and directs the synthesis of a polypeptide. In vitro the RNA transcribed from the rne gene directs the synthesis of a number of polypeptides, one of which is identical in size to the in vivo product of the rne gene. A rabbit reticulocyte cell free extract programmed with this RNA produced RNase E activity. Thus, it is evident that the rne gene is the structural gene for RNase E. However, the in vivo product of the cloned RNase E gene is more thermolabile than the chromosomal gene product. When cells containing the rne plasmid were treated with chloramphenicol, the pre-existing RNase E became less heat labile with time. This leads to the suggestion that in the cell RNase E undergoes post-translational modification(s). PMID- 8364099 TI - Effect of flavins on the rate of proteolytic digestion of muscle glycogen phosphorylase b. AB - The kinetics of tryptic proteolysis of rabbit skeletal muscle phosphorylase b has been registered by the diminishing of protein fluorescence intensity at lambda = 335 nm (excitation at 290 nm) or by the disappearance of the enzyme activity (0.02 M Hepes buffer, pH 6.8, 37 degrees C). The first procedure showed that flavins (riboflavin, FMN, FAD) protected the enzyme against tryptic digestion. Microscopic dissociation constants for the complexes of phosphorylase b with riboflavin, FMN and FAD were calculated from dependences of the initial digestion rate on the flavin concentration. They where equal to 30 +/- 1, 15.8 +/- 0.2 and 36 +/- 1 microM, respectively. No influence of FMN on the rate of the tryptic hydrolysis of phosphorylase b was observed when using the second procedure (enzyme activity test). FMN completely prevents the formation of 69-, 81- and 85 kDa fragments during 20 min incubation of phosphorylase b with trypsin. PMID- 8364100 TI - Does histone H1 bind specifically to the nuclear factor I recognition sequence? AB - The issue of whether histone H1 possesses specificity of binding to certain nucleotide sequences in DNA is of fundamental importance to the suggested role of the linker histone in the regulation of gene transcription. The purpose of the present study was to reinvestigate the specificity of binding of histone H1 to the putative nuclear factor I (NFI) recognition sequence suggested by a previous report in the literature. The interaction of purified mouse liver histone H1 with a synthetic oligonucleotide representing the natural NFI binding site from the adenovirus 2 origin of replication cloned in pBR322 has been studied by filter binding and a solid-phase procedure performed on nitrocellulose filter immobilized protein dots. No indication of specific interactions of the lysine rich histone H1 with the NFI recognition sequence was obtained. PMID- 8364101 TI - [First impressions regarding the use of expandable esophageal prosthesis]. AB - The authors report their views on the treatment of unoperable neoplastic esophago gastric stenoses with Nitinol prostheses. Despite a number of advantages (reduced trauma, greater tolerability) in relation to plastic prostheses, the paper highlights some problems (difficulty of unfastening, incomplete opening) which may be eliminated by improved materials. PMID- 8364102 TI - [Serum lipids and biliary sludge during pregnancy]. AB - We have examined serum lipids and apoprotein levels and the formation of biliary sludge in 56 pregnant women. During pregnancy, 8 women showed biliary sludge which disappeared after delivery. Pregnant women with sludge had serum levels of total cholesterol, triglycerides, LDL-cholesterol and apo-B higher than women without sludge, although it was not statistically significant. Moreover, these women had serum levels of HDL-cholesterol and apoA1 significantly lower and LDL/HDL and apoB/apoA1 ratio significantly higher than the women without sludge. Thus, biliary sludge seems to be associated with serum lipid and apoprotein variations. Further investigations are required to clarify if these variations are also expressed in the bile. PMID- 8364103 TI - [Endoscopic aspects of primary non-Hodgkin's lymphoma of the stomach]. AB - The introduction of endoscopy has led to a striking improvement in the diagnosis of primary non-Hodgkin gastric lymphomas due to the possibility of viewing the lesions directly and performing histological and cytological biopsies. Endoscopic findings are however polymorphous and may present difficulties of interpretation. The aim of this study was to re-examine the endoscopic data in 40 cases (25 M and 15 F) of gastric lymphoma observed during the period 1983-1990. There were three main endoscopic findings: ulcerated lesions (55%), infiltrating lesions (40%) and polypoid lesions (5%). In 75% of cases the biopsies carried out during the course of endoscopic examination were positive for lymphoma; in 7.5% of cases histological diagnosis was made using macrobiopsies carried out using a diathermic loop whereas in 17.5% it was made during the course of laparotomy. It may be possible to make further progress towards an early diagnosis following the introduction of echoendoscopy which will allow an in-depth evaluation of lesions and the involvement of lymph node stations and nearby organs. PMID- 8364104 TI - [Endoscopic and pharmacologic treatment with omeprazole of upper digestive hemorrhage]. AB - Upper gastrointestinal bleeding is still a subject much discussed as much for the diagnostic approach and as by the therapeutic decisions read. The authors present their experience of the treatment of upper gastrointestinal bleeding not caused by portal hypertension or by neoplasm. The patients undergo emergency endoscopy by haemostatic treatment if necessary and pharmacological therapy by omeprazole. The evaluation criteria are: stopped bleeding, the need of blood transfusion, the healing of the bleeding site. Stopped bleeding has been watched at first endoscopic check in 85% of patients; only 26 blood units has been necessary; the complete healing of bleeding injury happened not later than 30 days. PMID- 8364105 TI - [Evaluation of the cost of maintenance therapy (6 months) with 150 mg ranitidine vs 20 mg omeprazole vs 20 mg omeprazole every other day in duodenal ulcer]. AB - Prevention of ulcer relapse and of its complications is a problem which remains to be solved. Our study involved 250 patients, with healed duodenal ulcer. We evaluated efficacy and costs of three different maintenance therapies: ranitidine 150 mg/day, omeprazole 20 mg/day every other day and omeprazole 20 mg/day. Six months later, we found the incidence of relapse to be 24.4% (32/131) in the once a-day ranitidine group, 19.7% (13/66) in the day every-other-day omeprazole group, and 3.8% (2/53) in the once-a-day omeprazole group. Further, we evaluated costs relative to relapsing patients, and total costs for each treatment group. From these data, we conclude that personalized maintenance therapy with omeprazole is the most cost-effective: a dosage of 20 mg/day is extremely effective in maintaining remission, and is therefore most indicated in patients at risk; omeprazole 20 mg/day every-other-day affords better compliance, lower costs and fewer relapses with respect to standard H2-antagonist dosages. PMID- 8364106 TI - [Comparison of 3 methods of preparation for colonoscopy]. AB - We compared three cleansing methods of preparation for colonoscopy in 150 patients: the first containing a mixture of cathartics, especially sennosides: the second containing polyethyleneglycol: the third containing a mixture of monosodic monohydrated and bisodic heptahydrated phosphate. We evaluated the tolerability, the compliance and the side effects of the preparations. Regarding the evaluated parameters, it was found that the mixture of monosodic and bisodic heptahydrated phosphate was more valid than the other preparations. PMID- 8364107 TI - [Ischemic hepatitis. Description of 4 cases and review of the literature]. AB - We studied four patients who presented a striking elevation of blood transaminases suggesting acute hepatitis. The post mortem histological examination of the liver revealed centrolobular necrosis that is commonly diagnosed as ischaemic hepatitis. The liver necrosis arose from heart failure which was worsened by an acute anaemia in one patient and by a severe hypoxemia, due to respiratory failure, in another. In three subjects there was evidence of disseminated intravascular coagulation that may be responsible for aggravating the condition of liver hypoxia. The authors also review the literature on the various aspects of ischaemic hepatitis. PMID- 8364108 TI - [Protein C: mechanisms of activation and anticoagulant effect]. AB - The mechanism of functioning of protein C can briefly be presented as follows. Thrombin and factor Xa formed in the blood via coagulation, interact with endothelial thrombomodulin and thereby activate protein C circulating in the blood. The activated protein C inhibits factors V and VIII and, in so doing, blocks the further production of thrombin. In this way protein C intermediates the loop of the negative feedback and prevents excessive thrombin generation. Besides, activated protein C enhances fibrinolysis, causing the release of the tissue plasminogen activator. Activated protein C is inhibited by a heparin dependent inhibitor and alpha 1-antitrypsin and is then excreted from the organism. Congenital deficiency of protein C gives rise to thromboses; thrombotic diseases of various etiology are accompanied by protein C decline in the blood. Injection of exogenous protein C into the blood increases the anticoagulant activity of the blood and produces an antithrombotic effect. PMID- 8364109 TI - [Substrate specificity of T4 RNA-ligase: the role of a purine nucleotide base in forming a covalent AMP-RNA-ligase complex]. AB - The NTP binding site of bacteriophage T4 RNA-ligase (EC 6.5.1.3) was studied using several ATP analogs modified in the purine moiety of the nucleotide at positions 1, 2, 6 and 8: adenosine-N'-oxide 5'-triphosphate (I), 6-chloropurine riboside 5'-triphosphate (II), 6-mercaptopurine riboside 5'-triphosphate (III), 1,N6-ethenoadenosine 5'-triphosphate (IV), 8-sulphoadenosine 5'-triphosphate (V), 8-bromoadenosine 5'-triphosphate (VI), inosine 5'-triphosphate (VII) and guanosine 5'-triphosphate (VIII). For all of the ATP analogs under study a reversible inhibition was demonstrated. These analogs appeared to be competitive inhibitors of the T4 RNA-ligase adenylation reaction and only V, VI and VII were efficient as substrates. The kinetic parameters for the competitive inhibition, (I50, Ki) were determined. A putative structure for the T4 RNA-ligase active site was proposed. PMID- 8364110 TI - [Transport of ions into human erythrocytes in various forms of hemolytic anemia: a correlation analysis]. AB - The activity of Na+, K(+)-ATPase (ouabain-inhibited 86Rb influx), Na+, K+ cotransport (ouabain-insensitive furosemide-inhibited 86Rb or 22Na influx), Na+/Na+ exchange (ouabain-insensitive phloretin-inhibited 22Na influx) and Na+/Li+ exchange (ouabain-insensitive Na0(+)-depended Li+ efflux) as well as the passive permeability of the erythrocyte membrane for Na+, K+ and Li+ have been studied in patients with primary (microspherocytosis, hemoglobinopathy) and secondary (autoimmune) hemolytic anemia. The activities of the Na+, K(+)-pump and Na+, K(+)-cotransport were increased in patients with microspherocytosis-by 45% and 70%, respectively. In patients with hemoglobinopathy the Na+/Li+ exchange and passive permeability for K+ were increased 2-3-fold in comparison with the control with the control group. The increased passive permeability for K+ may partly be due to the increased K+, Cl(-)-cotransport. In patients with autoimmune anemia the 3-fold increase in the passive permeability for monovalent cations and the 2-fold increased activity of Na+, K+ cotransport were found. There was no significant correlation between the Na+/Na+ and Na+/Li+ exchange which suggests that the cellular mechanisms of activity control in those ion transport systems differ essentially. No correlation was found between the passive permeability for Na+ and K+ either. These data indicate that simple diffusion (leakage) is not the only pathway for the passive permeability of the erythrocyte membrane for monovalent cations. PMID- 8364111 TI - [The effect of glycolipids [correction of glycoproteins] on the oligomeric structure and catalytic activity of alpha-L-fucosidase from human kidneys]. AB - alpha-L-Fucosidase (EC 3.2.1.51) has been isolated from human kidney and purified to homogeneity by affinity chromatography on concanavalin A-Sepharose and fucosylamino-Sepharose. The catalytic activity and oligomeric structure of the enzyme were studied in a reversed micelle system of aerosol OT in octane. Depending on the degree of hydration (a parameter determining the geometrical sizes of the inner aqueous cavity of micelles), fucosidase is present within micelles as 53 kDa monomers, 110 kDa dimers, 230 kDa tetramers and 480 kDa octamers. Association of the monomers into tetra- or octamers causes a 3-4 fold increase in the specific catalytic activity of alpha-L-fucosidase. At pH and ionic strength values corresponding to intralysosomal ones alpha-L-fucosidase is isolated from tissues exclusively in a tetrameric form. After treatment with sodium cholate and subsequent dialysis this tetramer irreversibly dissociates into monomers; this reaction is accompanied by 2-3-fold decreases in the specific catalytic activity of alpha-L-fucosidase. The enzyme tetrameric structure and specific catalytic activity may be reconstituted in a reversed micelle system in the presence of glycolipids-di- and trihexosylceramides, GM1-ganglioside and a mixture of bovine brain gangliosides. PMID- 8364112 TI - [Isolation and characteristics of Bacillus megaterium metalloproteinase]. AB - Stepwise application of affinity chromatography on bacitracin-silochrome, gel filtration on Acrylex P-10, rechromatography on bacitracin-Sepharose 4B and gel filtration on Sephadex G-15, a homogeneous metalloproteinase (M(r) = 35,000 Da) has been isolated from the cultural filtrate of B. megaterium strain 599. The amino acid composition and N-terminal sequence (20 amino acids) of the enzyme have been determined. The proteinase is not inhibited by diisopropyl fluorophosphate, is inhibited by o-phenanthroline, EDTA, and Zn2+, and is activated by Co2+. The enzyme has a peak activity at 60-65 degrees C. The maximum of the enzymatic activity after hydrolysis of synthetic substrates is at pH 6.5 7.0. The enzyme is stable at pH 7.0-9.0 and retains its stability at 45-60 C for several hours. In acid media the enzyme undergoes irreversible inactivation. The dependence of kcat/Km on pH points to the involvement of an ionogenic group with pKa 7.5 in the catalytic act, most probably of the imidazole group of histidine. The metalloproteinase hydrolyzes synthetic peptide substrates at the bonds formed by the amino groups of hydrophobic amino acids-Phe, Leu, Ile and Val. PMID- 8364113 TI - [A new method of isolation and purification of SsoII restriction endonuclease]. AB - A new method for isolation and purification of restriction endonuclease SsoII which results in a homogeneous preparation suitable for all types of fine physico chemical assays has been elaborated. The procedure includes four chromatographic steps: fractionation on butyl-Toyopearl, combined chromatography on SP-Toyopearl and phosphocellulose PII, and chromatography on DEAE-Toyopearl and on QAE Toyopearl. The use of fast flow sorbents (Toyopearl) makes it possible to reduce the time needed for the separation of proteins and to optimize the fractionation conditions, thus avoiding the dialysis between the chromatographic steps which significantly decreased the enzyme activity yields in previous purification schemes. The isolation of restriction endonuclease SsoII by the new method usually takes four days. PMID- 8364114 TI - [Renaturation of bacterial metalloproteinases]. AB - After denaturation by phenol or acid ethanol bacterial metalloproteinases secreted by Bacillus thermoproteolyticus and Bacillus megaterium cells can be renatured by dissolution in 99.7% formic acid with subsequent dilution of the solution and its neutralization with an appropriate amount of an alkali. Renaturation is optimal at pH 9.0 in the presence of 30% glycerol as stabilizer, Ca2+ and Zn2+ ions needed for the formation of a native structure and reconstitution of the enzyme catalytic center. The active enzyme yield is 60-80%. Reactivated metalloproteinases retain their enzymatic properties, amino acid composition and molecular mass. Under these conditions autolysis of metalloproteinases does not significantly influence their renaturation. PMID- 8364115 TI - [Co-precipitation of pepsin with products from the enzymatic synthesis of peptides as a factor limiting the effectiveness of the enzyme]. AB - Porcine pepsin behaviour during the synthesis of peptide p-nitroanilides and esters has been studied. In many cases, especially when long-chain peptides, such as Z-Ala-Ala-Phe-Leu-Ala-Ala-OMe, were synthesized, pepsin disappeared from the solution, being entrapped by the product precipitate rather than inactivated. Sorption of the enzyme on the product might be partially responsible for this effect. The active enzyme could be eluted from the precipitate by NaCl and isopropanol. Non-proteolytic proteins (lysozyme, bovine albumin, carbonic anhydrase) could also co-precipitate with pepsin. PMID- 8364116 TI - [IgG, modified with coproporphyrin I and the possibility of direct measurement of the antigen-antibody complex]. AB - Modification of rabbit IgG by coproporphyrin I activated by Woodward's reagent K as well as antigen-binding and fluorescent properties of coproporphyrin-IgG have been studied. It was shown that coproporphyrin I modified IgG retains its capacity to bind the antigen. The formation of the immune antigen-antibody complex increases the intensity of coproporphyrin-IgG fluorescence. PMID- 8364117 TI - [Interaction of serum albumin with apoprotein E and very low density lipoproteins in human blood]. AB - The complex formation between apolipoprotein E (apoE) isolated from human plasma very low density lipoproteins (VLDL) and human serum albumin (HSA) in both native and fully reduced states has been studied. Using measurements of fluorescence anisotropy and fluorescence intensity of the fluorescein-labelled apoE, the elution profiles of the apoE/HSA complex and the kinetics of the protein cross linking within the complex by a water-soluble bifunctional reagent, the existence of a kinetically unstable complex of apoE with native albumin has been shown. The complex became more stable after the reduction of the S-S links in the albumin molecules capable of forming aggregates under these conditions. The interaction between native HSA as opposed to the fully reduced one and the isolated VLDL particles was far more pronounced, apparently due to the existence of amphipathic alpha-helical regions. It is suggested that the ability of the apolipoprotein to interact with albumin is determined by the inner stability of the albumin molecular structure and that the complexes detected in vitro may be regarded as a new transport form of apolipoproteins in a lipid-free form in the serum. PMID- 8364118 TI - [Affinity modification of proteins, binding nucleic acids in mammalian cells, by alkylating derivatives of oligonucleotides]. AB - Using the 32P-labelled alkylating oligonucleotide derivative (pT)16, the oligonucleotide interaction with mammalian cells has been studied. The majority of fibroblastoid cell lines tested in this study (COS-1, vero, L-671, Ag 17-1, CHO, B7) as well as mouse hepatocytes were found to contain proteins specifically interacting with oligonucleotides. Cells of Ag 17-1 and COS-1, apart from the 79 kDa protein specific for all fibroblast lines, contained also a protein with a molecular mass of 83 kDa. In BALB/c mouse hepatocytes the 83 kDa protein is the major oligonucleotide binding protein. Analysis of concentration dependencies of specific modification of receptor proteins in liver cells has made it possible to determine the values of constants for the oligonucleotide derivatives binding to the protein. The binding constant for the alkylating oligonucleotide derivative pT16 and the corresponding phosphothioate oligonucleotide has been found to be equal to 5 x 10(6) M-1. PMID- 8364119 TI - [The effect of progesterone and tamoxifen on EGF-dependent activation of phospholipid turnover in uterine and breast tumor cells]. AB - The in vitro effects of the epidermal growth factor (EGF) and progesterone on phospholipid turnover in cells of 19 human adenocarcinomas (postsurgical material) have been studied. In 58% of tumours EGF increased the 32P incorporation into two basic cell phospholipids--phosphatidylcholine and phosphoinositides. In EGF-insensitive cells progesterone induced no noticeable changes in the basal level of phospholipid metabolism. However, in 10 out of 11 positively responding to EGF adenocarcinomas progesterone inhibited the EGF dependent activation of 32P incorporation into the phospholipids already on the 15th min after its addition to the cells. Analysis of effects of EGF and the anti estrogen drug tamoxifen on phospholipid turnover in 22 human mammary tumours did not reveal any significant differences in tamoxifen effect on tumour cells differing in their sensitivity to EGF. Independently of cell sensitivity to EGF, tamoxifen caused some decrease in the 32P incorporation into phosphatidylcholine but increased the label incorporation into phosphoinositides. Tamoxifen added to tumour cells prestimulated with EGF or 17 beta-estradiol failed to abrogate the effect of these compounds on phospholipid turnover. At the same time, treatment of cells with the protein kinase C activator 12-O-tetradecanoyl-phorbol-13 acetate fully inhibited the effect of tamoxifen on phospholipid metabolism. The results obtained suggest that the EGF-dependent activation of intracellular phospholipid turnover is under the negative control of progesterone. As for tamoxifen, its effect on cells is independent of EGF and consists, apparently, in the inhibition of protein kinase C activity. PMID- 8364120 TI - [Properties, production, and practical uses of alkaline phosphatase]. AB - Literary data concerning the properties, isolation, purification and practical applications of alkaline phosphatase isolated from different sources are reviewed with special reference to the macromolecular structure and action mechanism of the enzyme in the reactions of phosphomonoester hydrolysis. The practicality of alkaline phosphatase as a helpful tool in conducting enzyme-linked immunoassays is demonstrated. PMID- 8364121 TI - [Tannin-mediated attachment of avidin to erythrocytes does not cause their lysis by complement]. AB - It was shown previously that avidin attachment to biotinylated erythrocytes induced their lysis by a homologous complement via an alternative pathway. This phenomenon hindered the use of avidin-coated immuno-erythrocytes as carriers for drug targeting. In the present work it has been demonstrated that avidin attachment to erythrocytes via a cross-linking reagent (tannin) does not induce any lysis by the complement. Tannization provides an attachment of up to 5 x 10(5) avidin molecules per erythrocyte which is commensurate with the value obtained after treatment with biotin esters. However, in contrast with biotinylated avidin-coated erythrocytes tannized cells are not lysed by the complement, while tannization itself does not diminish the erythrocyte sensitivity to lysis by the complement in the presence of activators (hemolytic antibody or activators of the alternative pathway). The avidin-induced lysis by the complement depends on the mode of avidin attachment to erythrocytes. Complement-resistant avidin-coated tannized erythrocytes bind biotinylated immunoglobulins and may therefore be used as carriers for drug targeting. The use of hemolytic antibody in biotinylated immunoglobulins attached to avidin-coated erythrocytes provides their controlled lysis by a complement activated via a classical pathway. PMID- 8364123 TI - [ATPase activity and K+ transport in membranes of anaerobically grown trk-mutants of Escherichia coli]. AB - A notable (twofold) increase in N,N'-dicyclohexylcarbodiimide (DCCD)-sensitive ATPase activity at increasing concentrations of K+ ion--from zero to 100 mM was found in isolated membranes of anaerobically grown E. coli. This was also observed during changing of Rb+ concentration (but not that of Na+, CL- or NO3-) and only in the wild precursor strain and trkG (but not in trkA, trkE, or trkH mutants). The DCCD-sensitive ATPase activity did not depend on K+ concentration in membranes of bacteria grown in the presence of NaNO3. TrkG or trkH mutants of E. coli with unc-deletions displayed a slight ATPase activity which was insensitive to DCCD. The growth of the trkG mutant, unlike other trk mutants, did not depend on K+ concentration above 0.4 mM. In this case accumulation of K+ in this mutant under positive osmotic shock was notably higher. These results suggest that K(+)-dependent DCCD-sensitive ATPase activity in membranes of anaerobically grown bacteria depends critically on the functioning of F1F0-ATPase and Trk of the K+ uptake system and may be explained by a direct relationship between these transport systems. It is also probable that the trkG gene has no functional activity in anaerobically grown bacteria. PMID- 8364122 TI - [Some features of enkephalin metabolism in the rat brain after administration of bestatin]. AB - The effect of a single bestatin dose on enkephalin content, activities of enkephalin convertase, enkephalinase A and aminopeptidases as well as on the level of specific binding of (3H) (D-Ala-2,D-Leu-5)enkephalin in rat midbrain (including hypothalamus) and striatum has been studied. Using ANOVA and correlation analyses, the relationship between the changes in these parameters has been established. The different responses of the enkephalin system of rat brain seem to be due not only to differences in the ratios of the "enkephalinase" and "aminopeptidase" pathways of enkephalin catabolism but, also, to structural peculiarities of enkephalin-containing conduction tracts. PMID- 8364124 TI - [Supramolecular structure based on protein conjugates with polyalkyleneoxides. Complexes with beta-cyclodextrin]. AB - The reaction of the complex formation between beta-cyclodextrin and alpha chymotrypsin conjugates with two-component ethylene oxide copolymers with propylene oxide has been described for the first time. The complex formation has been shown to depend on the mode of distribution of the polymer chains in the conjugate. The complex is a crystalline water-insoluble compound; its stoichiometric composition has been determined. The alpha-chymotrypsin conjugate with polyethylene glycol forms a water-soluble complex with beta-cyclodextrin. PMID- 8364125 TI - [Study of the interaction of DNA primase from calf thymus and human placenta with oligonucleotides matrices of various length and structure]. AB - Human placenta DNA-primase as a component of the DNA-polymerase alpha-primase multienzyme complex was examined with a view of establishing the dependence of Km values in the reaction of oligoriboadenylate synthesis from ATP on the length of a poly(dT) template. The pKm values increased linearly up to ten monomeric units of the oligo(dT)n template. These data favour oligo(dT)10 as an optimal template covered by the active site of this enzyme. The DNA-primase catalyzed processively the synthesis at each polymerization cycle of a unique length primer (7-10 nucleotides) as follows from the analysis of the primer length and its distribution with time. It is suggested that the 10 mer DNA-RNA duplex of the template and the primer is a critical size for dissociation of primase and further elongation of the primer by DNA-polymerase in the presence of dNTP. PMID- 8364126 TI - [Proteolytic enzymes in human lymphocytic leukemia cells. II. Comparative characteristics of proteolytic enzymes and their inhibitors in three differing types of lymphoid cells]. AB - A comparative study of proteolytic enzymes and their inhibitors in three human leukemic lymphoid cell populations has been carried out. The lysates of all lymphoid cells contained cathepsins D, B, L and H as well as serine trypsin-like proteinases, several aminopeptidases, dipeptidyl aminopeptidase IV and plasminogen activator (urokinase type). The activities of individual proteinases and their ratios in all cell types under study varied essentially, suggesting that lymphoid cells with different functions have different sets of proteolytic enzymes. FPLC chromatography of the lysates revealed the presence of inhibitors of cysteine and serine trypsin-like proteinases. The procedure for isolation of cathepsins D, B, L and H and of their inhibitors has been proposed and partially purified protein preparations obtained. Some properties of cathepsins B and L and those of their inhibitor have been examined. PMID- 8364127 TI - [The effect of new synthetic cholesterol derivatives on cholesterol metabolism in cultured rabbit hepatocytes]. AB - The effects of three novel synthetic derivatives of cholesterol with ethoxy (I), aminoethoxy (II), azidoethoxy (III) and toluenesulfonyloxyethoxy (IV) groups in the 3 beta-hydroxy position of cholesterol on cholesterol synthesis as well as on apolipoprotein B and bile acid secretion in cultured rabbit hepatocytes have been studied. 3 beta-(2-hydroxyethoxy)-cholest-5-en (I) was used as a standard. It was found that the inhibiting effect of these compounds on cholesterol synthesis depends on their structure. Compound II (1 microgram/ml), which inhibited acetate incorporation into cholesterol by 30-50%, appeared to be the most effective among the other compounds tested. This derivative had no effect on the production of bile acids. Compound III was less effective, while compound IV had no effect on cholesterol synthesis. All the compounds under study reduced by 20-36% the secretion of the total apolipoprotein B as measured by the enzyme-linked immunosorbent assay (ELISA). None of the synthetic cholesterol derivatives influenced the leucine incorporation into the total protein fraction. The results obtained indicate that 3 beta-(2-aminoethoxy)cholest-5-en, the most effective compound among other cholesterol derivatives tested in the study, can serve as a basis for synthesizing novel cholesterol derivatives able to inhibit cholesterol biosynthesis in liver cells and to decrease the secretion of very low density lipoproteins in cultured rabbit hepatocytes. PMID- 8364128 TI - [The effect of the composition of phospholipid bilayer membranes on the steady state kinetic transfer of protons]. AB - When the hydrogen ion flux was induced by nigericin across the planar bilayer lipid membrane (BLM) with the bulk pHs being equal at the opposite sides of the BLM, the formation of the boundary potential difference (delta phi b) on the BLM was observed using the method of the inner membrane field compensation. The increase in the buffer (citrate, phosphate, MES) concentration caused a decrease in the delta phi b. The latter is generated in the presence of phosphatidylserine in membrane-forming solutions only. It was assumed that the steady state difference of the surface hydrogen ion concentration is created under conditions of equal pHs near the BLM surface. In another experimental series the monensin mediated formation of the surface protein concentration difference gave rise to the formation of a potassium ion gradient induced by nigericin. Thus, a possibility of performing work due to the surface proton concentration gradient was demonstrated. The relevance of these findings to the processes of energy transduction during membrane phosphorylation in mitochondria and chloroplasts is discussed. PMID- 8364129 TI - Gastric anti-secretory, mucosal protective, anti-pepsin and anti-Helicobacter properties of ranitidine bismuth citrate. AB - Ranitidine bismuth citrate is a novel compound formed from ranitidine and a bismuth citrate complex. In conscious dogs, ranitidine bismuth citrate had similar activity to ranitidine hydrochloride as an inhibitor of histamine-induced gastric acid secretion when oral doses containing equivalent amounts of ranitidine base (0.1 or 0.3 mg/kg) were compared. In the rat, ranitidine bismuth citrate (3-30 mg/kg p.o.) prevented gastric mucosal damage induced by ethanol (fundic damage) and indomethacin (antral damage). Ranitidine hydrochloride and tripotassium dicitrato bismuthate were also effective against indomethacin induced damage, but were both significantly less potent than ranitidine bismuth citrate in this model. Ranitidine hydrochloride was inactive against ethanol induced damage. In vitro, ranitidine bismuth citrate (1 mmol/L) inhibited human pepsin isoenzymes 1, 2, 3 and 5. Pepsin 1 was inhibited to a similar extent by ranitidine bismuth citrate, bismuth citrate and tripotassium dicitrato bismuthate at concentrations equivalent to 1 mmol/L bismuth, but ranitidine (1 mmol/L) was inactive. Ranitidine bismuth citrate was more potent than tripotassium dicitrato bismuthate as an inhibitor of pepsins 2, 3 and 5. Ranitidine bismuth citrate inhibited both Helicobacter pylori (effective concentration 4-32 micrograms bismuth/ml) and H. mustelae (1-4 micrograms bismuth/ml); similar results were obtained with tripotassium dicitrato bismuthate. Bismuth citrate was slightly less effective, and ranitidine hydrochloride was inactive (> 125 micrograms/ml). In ferrets naturally colonized with H. mustelae, oral treatment with ranitidine bismuth citrate, 12 or 24 mg/kg twice daily for 4 weeks, caused a dose related clearance of H. mustelae. Qualitatively similar results were obtained in a small study with tripotassium dicitrato bismuthate and bismuth citrate. PMID- 8364130 TI - Prospective study of the need for long-term antisecretory therapy in patients with Zollinger-Ellison syndrome following successful curative gastrinoma resection. AB - A long-term cure is now possible in more than 30% of selected patients with Zollinger-Ellison syndrome who undergo gastrinoma resection. The need, however, for continued gastric acid antisecretory therapy in these patients remains controversial. The current study was designed to determine whether post-operative antisecretory therapy is needed in patients who have undergone successful gastrinoma resection and, if so, to attempt to define criteria with which to identify patients who require therapy. Twenty-eight consecutive patients who had previously undergone curative gastrinoma resection were prospectively studied. When antisecretory therapy was discontinued, 43% (12/28) of these patients developed gastro-oesophageal reflux, diarrhoea, acid-peptic symptoms or endoscopic evidence of acid-peptic disease within 2 weeks and were deemed to have failed a trial of antisecretory drug withdrawal. The remaining 57% (16/28) of patients who successfully discontinued antisecretory therapy were followed for a mean time of 31 months after withdrawal of therapy. Analysis of acid output studies pre-operatively, as well as at the time of drug withdrawal, demonstrated that patients who were unable to discontinue antisecretory therapy exhibited higher pre-operative maximal acid output values and higher basal acid output values at the time of attempted drug withdrawal than patients who were able to discontinue therapy. Despite these findings, there was significant overlap in acid output values between groups so that it was not possible to define specific acid output criteria for successful drug withdrawal. Pre-operative clinical characteristics, such as the presence or absence of gastro-esophageal reflux or acid-peptic disease, or post-operative laboratory values, such as the fasting serum gastrin level, did not correlate with the ability to discontinue antisecretory therapy. We conclude that following successful curative gastrinoma resection, 40% of patients still require antisecretory therapy and that both symptom evaluation as well as upper endoscopy should be used to guide attempted drug withdrawal. Although patients who are not able to discontinue therapy have significantly higher acid output measurements than those who are able to discontinue therapy, neither acid output criteria nor any other laboratory or clinical characteristics are able to predict the need for continued antisecretory therapy in these patients. PMID- 8364131 TI - A placebo-controlled investigation of duodenal ulcer recurrence after withdrawal of long-term treatment with ranitidine. AB - Ninety-two patients with duodenal ulcer disease, who had received long-term continuous treatment with ranitidine for an average of 7.5 years, participated in a double-blind, placebo-controlled study to determine whether stopping ranitidine resulted in ulcer recurrence. Patients were randomized to continue with ranitidine (n = 46) or to receive placebo (n = 46) and were followed up for six months. Treatment failure was defined as the first symptomatic recurrence of ulcer. The occurrence of epigastric pain during the follow-up period was significantly less frequent in the ranitidine group (13%) than in the placebo group (43%) (P = 0.001). At six months, 9% of the ranitidine group had developed ulcer recurrence, compared with 48% in the placebo group (P < 0.001, logrank test). Multivariate analysis using the Cox proportional hazards model showed that younger age (P = 0.041) and a long history of ulcer disease (P = 0.025) were risk factors for ulcer recurrence but gender, smoking and duration or dose of previous ranitidine treatment were not predictive of relapse during treatment with placebo. In conclusion, withdrawal of ranitidine after more than five years of continuous treatment results in almost half of the patients developing symptomatic ulcer recurrence within six months. Thus, long-term continuous therapy does not alter the natural history of duodenal ulcer disease. Younger patients and those with a long history of ulcer disease appear to be at increased risk of developing ulcer recurrence if long-term treatment is withdrawn. PMID- 8364132 TI - Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease. AB - The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO4) could restore thymic endocrine function in patients with Crohn's disease who showed decreased plasma concentrations of zinc and active thymulin, a zinc-dependent thymic hormone. Twenty-seven patients in clinical remission were randomly assigned to receive, for 3 months, one of the following treatments: 60 mg/day ZnSO4; 200 mg/day ZnSO4 or placebo. Plasma thymulin activity and zinc concentrations significantly increased only in patients treated with 200 mg/day ZnSO4. Lymphocyte subpopulations, within the range of normality before zinc supplementation, were unaffected by any of the administered treatments. In conclusion, low plasma concentrations of zinc and thymulin in Crohn's disease patients were restored by the administration of high doses of zinc. PMID- 8364133 TI - Effect of zinc therapy on natural killer cell activity in inflammatory bowel disease. AB - Disturbances in zinc metabolism have been documented in patients with inflammatory bowel disease. In this study we evaluated the effect of in vivo treatment with zinc on the in vitro natural killer cell activity in thirteen inflammatory bowel disease patients, with stable disease and mild-moderate disease activity, in a double-blind randomized cross-over trial. The results of our study show a long-lasting effect of in vivo zinc administration, which decreased peripheral blood natural killer cell activity in inflammatory bowel disease. PMID- 8364134 TI - The effects of 300 mg ranitidine at night, twice daily and four times daily on intragastric acidity in normal subjects. AB - The aim of this study was to compare to placebo the effects of 300 mg ranitidine nocte, b.d. and q.d. on intragastric acidity. The study was performed on healthy male subjects and intragastric acidity measured by radiotelemetry. All active treatments significantly decreased 24-hr acidity, with a median suppression of 61.0% with 300 mg ranitidine nocte, 77.7% with 300 mg b.d. and 78.0% with 300 mg q.d.s. There was no significant difference between the effects of two higher dose regimens; although the 300 mg q.d.s. suppressed daytime acidity more than 300 mg b.d. (88.9% vs. 77.8%), it suppressed nocturnal acidity less effectively (65.5%) than either 300 mg nocte (92.9%) or 300 mg b.d. (90.0%). These data suggest that only modest additional therapeutic acid inhibition can be achieved by increasing the dose of ranitidine above 600 mg daily. PMID- 8364135 TI - Rolling review: gastro-oesophageal reflux disease. PMID- 8364136 TI - Short report: high-dose omeprazole and amoxycillin in the treatment of Helicobacter pylori-associated duodenal ulcer. AB - Thirteen consecutive patients with active duodenal ulcer disease were assigned to a treatment schedule with high-dose omeprazole and amoxycillin. Duodenal ulcer was diagnosed endoscopically in all patients, at which time antral biopsies were taken for culture and histology. All were positive for Helicobacter pylori and histological gastritis. Treatment was for 2 weeks: 80 mg omeprazole daily plus 500 mg amoxycillin syrup t.d.s. in the first week, followed by 40 mg omeprazole daily in the second week. Repeat gastroscopy was performed 4 weeks after completion of treatment in all patients. Duodenal ulcer healing occurred in 4/13 patients. H. pylori eradication was achieved in 2/4 patients with healed ulcers and in 3/9 patients with persistent ulceration. This study suggests that a short period of treatment with high-dose omeprazole and amoxycillin achieves low rates of ulcer healing and H. pylori eradication. PMID- 8364137 TI - Short report: octreotide in the treatment of external pancreatic fistulas. AB - The efficacy of the long-lasting somatostatin analogue, octreotide, in the treatment of high-output pancreatic fistulas was investigated in this prospective, open study. Sixteen patients with post-operative pancreatic fistulas were treated with subcutaneous injections of octreotide 0.1 mg b.d. The output of the fistulas before the somatostatin therapy ranged between 190 and 570 ml/day. The therapy was begun on average 17 days following the appearance of the fistula (range 4 to 35 days). The decrease in volume one day after initiation of therapy ranged from 26% to 69%. By the third day of treatment the fistula volume decreased to 0-45% of the initial output. The treatment resulted in the closure of 14 of the 16 fistulas; the time to closure ranging from 3 to 15 days. The results suggest that octreotide is a useful adjuvant agent in the treatment of an external pancreatic fistula. PMID- 8364138 TI - Short report: effect of two prokinetic drugs on the electrical and motor activity of the small bowel in dogs. AB - The effects of trimebutine and domperidone, on the electrical and motor activity of the upper small bowel in dogs, were studied simultaneously by means of a suction electrode and a manometric catheter. Trimebutine, given during phases I and II of the migratory motor complex, was followed by a period of regular spike potentials and contractions; the increased motor activity was significantly greater when the drug was given during phase II. Domperidone, when injected in phase I, was followed by an irregular pattern of spike potentials and contractions of low amplitude. By contrast, activity was not augmented when the drug was given during phase II. We conclude that the effects of drugs, such as trimebutine and domperidone, on the canine small bowel are influenced by the phase of the migratory motor complex. PMID- 8364139 TI - Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood-acquired chronic hepatitis B virus infection. AB - Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2-week gap, by thrice weekly lymphoblastoid alpha-interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg), 'e' antigen (HBeAg) and HBV-DNA positive] became HBeAg and HBV-DNA negative during therapy and remained so after 12 months post-therapy follow-up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV-DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV-DNA negative but HBeAg positive at the end of follow-up. None of the eight untreated control patients seroconverted during an identical follow-up period. Two further patients were HBsAg and HBeAg positive but HBV-DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2-6 weeks after prednisolone withdrawal, loss of HBV-DNA 0-8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated. PMID- 8364140 TI - Efficacy of continuous therapy for peptic ulcer in controlled clinical trials. AB - Long-term studies have confirmed unequivocally the clinical efficacy of continuous therapy with H2-receptor antagonists in reducing the incidence of ulcer recurrence. However, studies have also reported varying relapse rates as a result of differences in study design, particularly the frequency of endoscopy and hence the detection of asymptomatic ulcer relapse. Risk factors for ulcer relapse include smoking, stress, previous history of frequent ulcer relapses, duration of disease for more than 10 years and concomitant administration of non steroidal anti-inflammatory drugs. In the prevention of relapse with H2-receptor antagonists, choice of agents also may influence the rate of relapse. A meta analysis of data from direct comparative trials indicates that recurrence rates of duodenal ulcer are significantly lower after one year of treatment with ranitidine (150 mg nocte) than with cimetidine (400 mg nocte). It has been claimed that patients with peptic ulcer disease can be successfully managed by intermittent courses of treatment with H2-receptor antagonists which are taken in response to the development of symptoms. However, high relapse rates (64-100%) have been reported during the first year of follow-up of patients who were receiving intermittent treatment with H2-receptor antagonists. High complication rates (haemorrhage 11.4%, perforation 1.2%) have also been reported over a seven year follow-up, while continuous treatment with H2-receptor antagonists significantly decreases the risk of haemorrhage in the event of ulcer recurrence. PMID- 8364141 TI - The need for long-term treatment of peptic ulcer. AB - Some 10% of the population in Western countries will suffer a duodenal ulcer or gastric ulcer at some time in their lives. Although there has been an improvement in the survival rate of patients with peptic ulcer haemorrhage, the mortality is still approximately 10%. There is evidence to suggest that peptic ulcer disease is a life-long condition and that ulcers remain active with an unchanged potential for complications such as haemorrhage and perforation. Over the past 15 years anti-ulcer drugs with different mechanisms of action have been developed, and their use results in complete healing of an ulcer in four to eight weeks. However, most patients experience recurrence of their peptic ulcer after discontinuation of the healing therapy. Studies of continuous H2-receptor antagonist therapy have shown that recurrence occurs less frequently than in untreated patients, is largely asymptomatic, and is rarely characterized by haemorrhagic complications. Limited data on therapy for the eradication of Helicobacter pylori suggest that this may be an alternative approach for selected patients. As protection afforded by H2-receptor antagonists remains undiminished over the course of several years and is also observed in ulcers which have bled in the past, the implementation of long-term management with these agents constitutes a rational policy. PMID- 8364142 TI - Management issues for debate: the problems in perspective. PMID- 8364143 TI - [Development of a lower limb model for the study of accident sequelae of vehicle pedestrian collisions]. AB - A major goal of the development and associated experimental investigation of car bumpers is the minimization of injuries in car-to-pedestrian collisions. Because the lower leg is particularly prone to injuries in a collision between a vehicle and a pedestrian, a lower leg model has been developed that makes it possible to simulate most of the processes occurring during an injury. In cooperation with the Institut fur Biomedizinische Technik (Institute for Biomedical Technology) of the University of Stuttgart and the Kunststofflabor des Fachbereiches fur Produktionstechnik (Institute for Production Methods) of the Fachhochschule fur Technik (Polytech) Esslingen, a muscle tissue model has been designed that makes it possible to simulate in a first approximation the mechanical behaviour of biological tissue under accident-specific pressure, or in the case of a crush injury. Initial prototypes were built with bone models of the tibia and fibula and with a skin model whose relevant material parameters were taken from the literature. PMID- 8364144 TI - [Experimental determination of muscle coordination of the lower extremity]. AB - In order to describe the lines of action of muscles acting on joints, data on the geometrical position of insertions and origins are needed. These are of fundamental relevance for the biomechanical analysis, in particular for the calculation of joint loading. A measuring device with an accuracy of 0.1 mm was designed and constructed for the collection of three-dimensional experimental data from wet anatomical specimens. The main design features of the device include a vertically adjustable stand on wheels and a rotatable scale ring with a radial pointer. After setting the reading, the apparatus permits the measurement of cylindrical coordinates The margins of the attachments of muscles acting on the hip and knee joints were measured in two specimens. Two extensive sets of morphological data are now available and can be used to create complex biomechanical computer models. PMID- 8364145 TI - [Possibilities for optimizing prosthetic management of leg amputees using quantitative movement analysis]. AB - First, the differences between natural and artificial lower extremities are discussed from a biomechanical perspective. Their effects on the motion can be quantified with the help of optoelectronic gait analysis. The differences in motion between natural gait and walking with an above-knee prosthesis are illustrated with an example. Based on this, design possibilities for the improvement of the gait of prosthesis wearers are considered, and the effects of these designs are documented with the help of gait analysis. Finally, the advantages of the simultaneous measurement of forces and motion are discussed, and with this, a new development direction of integrated gait analysis is described which could be of major significance. PMID- 8364146 TI - Characterization of p-bis(O-methylstyryl)benzene as a lifetime and anisotropy decay standard for two-photon induced fluorescence. AB - We describe the fluorescence spectral properties of p-bis(O-methylstyryl)benzene (bis-MSB) as a standard for time-resolved measurements of two-photon induced fluorescence. Bis-MSB displays the same single exponential intensity decay in several solvents for one- and two-photon excitation. The anisotropy decay displays the same single correlation time of one- and two-photon excitation. The amplitudes of the anisotropy decay are distinct for one- and two-photon excitation. At some excitation wavelengths the anisotropy amplitude appears to be solely the result of one- and two-photon photoselection, but at shorter wavelengths the anisotropy amplitudes are not related by single constant factor. The absorption range of bis-MSB makes it a suitable standard for one- and two photon excitation of intrinsic protein fluorescence and extrinsic fluorophores. PMID- 8364147 TI - Intensity and anisotropy decays of [Leu5] enkephalin tyrosyl fluorescence by 10 GHz frequency-domain fluorometry. AB - The technique of 10 GHz frequency-domain fluorometry was used to resolve the complex picosecond intensity and anisotropy decays of the tyrosyl emission of [Leu5] enkephalin. Enhanced resolution of anisotropy decay was obtained by using acrylamide quenching of the tyrosyl fluorescence and global analysis of the frequency-domain anisotropy data obtained with different amounts of acrylamide. The data indicates a 44 ps correlation time for local tyrosine motions, and a 219 ps correlation time for overall rotational diffusion of the pentapeptide. Our data are consistent with an initial loss of fluorescence anisotropy from r0 = 0.4 to a value of r0 = 0.326 occurring during the first two picoseconds after excitation. PMID- 8364148 TI - Stable self-sustained potential oscillations across a membrane filter impregnated with triolein. AB - When applying constant electric current, periodic self-sustained potential oscillations with high stability are observed across a membrane filter impregnated with triolein, placed between KCl and NaCl aqueous solutions. Stability, reproducibility and controllability of the oscillation are much improved by the application of constant electric current compared with those obtained without application of electric current. Relations among value of electric current, base potential and period of the oscillations are studied, and it is concluded that the oscillation period can be controlled by base electric potential. Effects of temperature on the oscillations are investigated, and it is shown that Arrhenius plots for both base conductance and conductance amplitude of each oscillation fitted well to an individual straight line and that values of activation energies are similar to those of bulk salt solutions. From all data obtained it is suggested that the oscillations occur as a result of rhythmic repetition of opening and closing of hole(s) in the membrane, which is due to breakdown and restoration of a part of the membrane. PMID- 8364150 TI - Energetics of corneal epithelial cell-ocular mucus-tear film interactions: some surface-chemical pathways of corneal defense. AB - The role of ocular mucous gel in the corneal epithelial hydration, lubrication, cleansing, wettability and defense against pathogens, is investigated based on a modified DLVO theory that accounts for the apolar, as well as polar, "acid-base" surface interactions. A strong polar repulsion keeps mucus in the form of highly hydrated "sloppy" gel, which does not adhere to the normal epithelium. Due to its strong electron donor type monopolarity, the mucus gel can form an effective barrier against contamination of the underlying epithelium by both the apolar (e.g., tear film lipids, cell debris) and the polar (e.g., hydrophilic bacteria) entities. In the absence of mucus, epithelial contamination becomes energetically favorable, which can also compromise its wettability by tears. Finally, a loss of polar surface properties can lead to adhesion of mucus to the cornea. PMID- 8364149 TI - Thermotropic behavior of phosphatidylcholine-glucosyl ceramide mixtures: effects of phospholipid acyl chain composition and interaction with water. AB - The thermotropic behavior of multilamellar vesicles composed of mixtures of dimyristoyl phosphatidylcholine-glucosyl ceramide and of egg phosphatidylcholine glucosyl ceramide was investigated using differential scanning calorimetry. Macroscopic demixing of the lipid components occurred when multilamellar vesicles were prepared from mixtures of glucosyl ceramide and egg phosphatidylcholine by conventional methods. This problem was overcome by a technique based on spray drying of the lipid mixture. The results obtained for the two systems are compared with data available for dipalmitoyl phosphatidylcholine-glucosyl ceramide mixtures (Biochemistry 22 (1983) 3497-3501). All three phosphatidylcholines perturb the complex thermotropic behavior of glucosyl ceramide. The data suggest that the interference with intermolecular interactions among glycosyl ceramide molecules by phospholipid molecules is related to the molecular miscibility of the two components. This is strongly dependent on the acyl chain composition of the phosphatidylcholine and the water activity of the ambient aqueous phase. PMID- 8364151 TI - Molecular dynamics simulation of the stability of a 22-residue alpha-helix in water and 30% trifluoroethanol. AB - A molecular dynamics (MD) simulation was performed on the alpha-helix H8-HC5, the C-terminal part of myoglobin (residue 132-153), under periodic boundary conditions in two different solutions, water and water with 30% (v/v) 2,2,2 trifluoroethanol (TFE), at 300 K to investigate the stability of the helix. In both simulations, the initial configuration was a canonical right-handed alpha helix. In the course of the MD trajectory in water (200 ps), the helix clearly destabilized and began to unfold after 100 ps. In the TFE solution, two stable parts of helical regions were observed after 70 ps of a 200-ps MD simulation, supporting the notion that TFE acts as a structure-forming solvent. PMID- 8364152 TI - Conformational transitions using molecular dynamics with minimum biasing. AB - The molecular dynamics algorithm (MD), which simulates intramolecular motions on the subnanosecond timescale, has been modified to allow the investigation of slow conformational transitions that do not necessarily occur spontaneously in MD simulations. The method is designated CONTRA MD (CONformational TRAnsitions by Molecular Dynamics with minimum biasing). The method requires the prior definition of a single conformational variable that is required to vary monotonically from an initial conformation to a final target conformation. The simulation is broken up into a series of short free MD segments, and we determine, after each segment of MD, whether or not the system has evolved toward the final conformation. Those segments that do not move the system in that direction are deleted. Those that do move it toward the final conformation are patched together sequentially to generate a single representative trajectory along the transition pathway. The CONTRA MD method is demonstrated first by application to the simultaneous C2'-endo to C3'-endo repucker and anti to syn N glycosidic torsion transitions in 2'-deoxyadenosine and then to the large-scale bending in phenylalanine transfer RNA. PMID- 8364153 TI - Synthesis and conformational study of peptides possessing helically arranged delta ZPhe side chains. AB - Z-Dehydrophenylalanine (delta ZPhe) possessing four oligopeptides, Boc-(L-Ala delta ZPhe-Aib)n-OCH3 (n = 1-4: Boc, t-butoxycarbonyl; Aib, alpha-aminoisobutyric acid), were synthesized, and their solution conformations were investigated by 1H nmr, ir, uv, and CD spectroscopy and theoretical CD calculation. 1H-nmr (the solvent accessibility of NH groups) and ir studies indicated that all the NH groups except for those belonging to the N-terminal L-Ala-delta ZPhe moiety participate in intramolecular hydrogen bonding in chloroform. This suggests that the peptides n = 2-4 have a 4-->1 hydrogen-bonding pattern characteristic of 3(10)-helical structures. The uv spectra of all these peptides recorded in chloroform and in trimethyl phosphate showed an intense maximum around 276 nm assigned to the delta ZPhe chromophores. The corresponding CD spectra of the peptides n = 2-4 showed exciton couplets with a negative peak at longer wavelengths, whereas that of the peptide n = 1 showed only weak signals. Theoretical CD spectra were calculated for the peptides n = 2-4 of several helical conformations, on the basis of exciton chirality method. This calculation indicated that the three peptides form a helical conformation deviating from the perfect 3(10)-helix that contains three residues per turn, and that their side chains of delta ZPhe residues are arranged regularly along the helix. The center to-center distance between the nearest phenyl pair(s) was estimated to be approximately 5.5 A. The chemical shifts of the delta ZPhe side-chain protons (H beta and aromatic H) for the peptides n = 2-4 indicated anisotropic shielding effect of neighboring phenyl group (s); the effect also supports a regular arrangement of the delta ZPhe side chains along the helical axis. PMID- 8364154 TI - The contribution of helical potential to the in vitro receptor binding activity of a neuropeptide Y N-terminal deletion fragment. AB - In its dimeric form neuropeptide Y (NPY) folds into a compact structure in which the antiparallel oriented proline and alpha-helices apparently associate to form a primitive hydrophobic core. To investigate the contribution of helical stability to the receptor binding activity of NPY and its N-terminal deletion fragments, we synthesized and studied the solution conformational properties and in vitro activities of NPY, N alpha-acetyl-NPY2-36, NPY15-36, N alpha-propionyl NPY15-36, and N alpha-succinyl-NPY15-36. NPY15-36 is significantly less helical than both NPY and N alpha-acetyl-NPY2-36, and this decreased helical potential is attributed to the absence of the intramolecular stabilizing interaction afforded by the proline helix in the latter analogues. However, in accord with the helix dipole model, the helical potential of NPY15-36 is significantly increased by N terminal succinylation, whereas propionylation has no effect. In addition to an increase in helical potential, N alpha-succinyl-NPY15-36 is 2.5 and 4.6 times more active than NPY15-36 and N alpha-propionyl-NPY15-36, respectively, and is equipotent with N alpha-acetyl-NPY2-36 in displacing 1 nM [3H]-NPY from specific binding sites in rat brain membranes. The demonstration of a positive correlation between % alpha-helix content and in vitro binding activity suggests that the helical potential of N-terminal NPY deletion fragments contributes to their in vitro activity in the rat brain, and that a second role of the proline helix might be to stabilize the receptor-active conformation of the NPY alpha-helix. PMID- 8364155 TI - Crystal structures of Boc-D- and L-Iva-L-Pro-OBzl: unturned conformation of Aib Pro sequence unaffected by replacement of Me with Et in Aib. AB - The crystal structures of the isovaline (Iva) containing dipeptides, Boc-D-Iva-L Pro-OBzl and Boc-L-Iva-L-Pro-OBzl, were determined by x-ray diffraction. The diastereomeric peptides were shown to adopt unturned conformations closely similar to each other (phi Iva 52 degrees, psi Iva 46 degrees, phi Pro -65 degrees, and psi Pro 143 degrees for D-Iva-L-Pro sequence and phi Iva 52 degrees, psi Iva 44 degrees, phi Pro -63 degrees, and psi Pro 148 degrees for L-Iva-L-Pro sequence). The Pro ring of each peptide was in C gamma-endo conformation. The unusually large angle CIva-NPro-C delta Pro values (131 degrees in both peptides) were observed, that was due to steric repulsion between the delta-methylene of Pro and the alkyl side chain of Iva residue. These conformations were essentially the same as that of the corresponding alpha-aminoisobutyric acid (Aib)-containing peptide Boc-Aib-L-Pro-OBzl. The result has demonstrated that replacement of either one of the two methyl groups of the Aib residue in Boc-Aib-L-Pro-OBzl with an ethyl group does not cause any significant change in the unturned conformation of the dipeptide. PMID- 8364156 TI - The hydration of proteins in nearly anhydrous organic solvent suspensions. AB - Water sorption isotherms at 27 degrees C have been measured for lysozyme and chymotrypsin in suspensions of toluene, di(n-butyl) ether, n-propanol, and a solution of 1M n-propanol in benzene. Sorption isotherms for the different suspensions are compared by converting solvent water content to the thermodynamic activity of water in each solvent. The sorption behavior is also compared to that for the two proteins hydrated from the vapor phase. At low water activities, all sorption isotherms are similar when compared on the basis of water activity. However, at higher activities, water sorption by the proteins in the organic suspensions is suppressed relative to the sorption of water vapor. The greatest suppression is observed for n-propanol, which suggests that the suppression may be due to a competition for water-binding sites on the protein by the organic solvent. Sorption isotherms at low water activities have also been predicted using a thermodynamic model in which it is assumed that water binds selectively to the ionizable residues on the surface of the protein. A comparison of predicted and measured sorption isotherms shows that the model can provide reasonable estimates of water sorption in nonpolar or moderately polar organic solvent suspensions at low levels of hydration. PMID- 8364157 TI - Proton magnetic resonance studies of bradykinin antagonists. AB - Bradykinin (BK) is a peptide hormone with sequence Arg1-Pro2-Pro3-Gly4-Phe5-Ser6 Pro7-Phe8-Arg9 and has been implicated in a multitude of pathophysiological processes such as the ability to lower systemic blood pressure and stimulate pain. BK analogues having bulky, beta-branched D-aliphatic residues at position 7 combined with bulky L-aliphatic residues at position 8 have now been observed to be strong antagonists. Conformational studies based on two-dimensional nmr experiments in methanol/water (80/20 v/v) were carried out on several such active antagonists in a polar solvent. Included in this study were the very active antagonists, [D-Arg0,Hyp3,Thi5,D-Cpg7,Cpg8]-BK [Cpg: alpha-cyclo-pentyl-glycine; Hyp: trans-4-hydroxy-L-proline; Thi: beta-(2-thienyl)-L-alanine] (I), [D Arg0,Hyp3,D-Cpg7,Cpg8]-BK (II), as well as its variant with D-Cpg7 replaced by Cpg7, namely [D-Arg0,Hyp3,Cpg7,Cpg8]-BK (III). A turn-like structure, which coexists with the extended conformation, was observed between residues 2 and 5 for the most active antagonists I and II, in direct correlation with the peptide activities. No turn-like structure was found for residues 6-9. In peptide III, a turn-like structure was not identified. The existence of a turn at the C-terminal end of bradykinin and its analogues has been predicted by empirical calculations and supported by nmr measurements. But the present nmr study on the most active antagonists (I, II) does not support this hypothesis. Instead, the data suggest that a turn-like structure between residues 2 and 5 could be important for antagonist activity. Finally, one weak inhibitor [D-Cpg7]-BK (IV) showed no defined secondary structure. PMID- 8364158 TI - Computer simulations of the flexibility of a series of synthetic cyclic peptide analogues. AB - The flexibility of a series of cyclic peptides derived from the epitope of a snake toxin is investigated using computer simulation techniques. Molecular dynamics (MD) simulations and vibrational analyses are performed on chemically constrained peptides modeled on the parent protein loop. In the 50 ps MD simulations, large variations in the atomic fluctuations are seen between the peptides, and can be related to the nature of the chemical constraints present in the molecules. Normal mode analyses are performed on energy-minimized configurations derived from the dynamics trajectories. The atomic fluctuations calculated from the normal modes are about 30% of those of the molecular dynamics for the more flexible peptides and 70% for the more constrained molecules. The calculated differences in flexibility between the molecules are much less significant in the harmonic approximation. PMID- 8364159 TI - The solution conformation of Ac-Pen-Arg-Gly-Asp-Cys-OH, a potent fibrinogen receptor antagonist. AB - The solution conformation of Ac-Pen-Arg-Gly-Asp-Cys-OH, a potent fibrinogen receptor antagonist, was characterized in DMSO-d6 by the combination of nmr and molecular modeling. The conformational space available to the peptide was explored using a distance geometry algorithm with distance constraints derived from 1H-nmr spectra. The dynamics of the peptide were examined by relaxation time measurements and low temperature studies. The results from the low temperature studies suggest that the peptide backbone does not exist in a single, well defined conformation but undergoes exchange between multiple conformers. This result is consistent with the inability to find a single structure that satisfies all the nmr-derived constraints. The constraints could only be satisfied by considering pairs of conformers to represent the experimental data. The low energy conformers comprise type II' or type V beta-turns with distinct side-chain directionality. The Arg-Gly-Asp portion of the ring is flexible and can be described by amide-plane rotations of the Arg-Gly and Gly-Asp peptide bonds. Although some backbone flexibility is evident, the incorporation of beta,beta dimethyl cysteine imparted greater conformational rigidity as compared to the previously studied cyclic pentapeptide, Ac-Cys-Arg-Gly-Asp-Cys-OH. PMID- 8364160 TI - Effects of a human urinary kininogenase (SK-827) on cerebral and cutaneous microcirculation in rabbits. AB - Pharmacological effects of a human urinary kininogenase (SK-827) on the cerebral and cutaneous microcirculation were studied in anesthetized normal rabbits. Intravenous administration of SK-827 had no effect on the diameter of pial arterioles or the hemoglobin content (IHb) of the brain. On the other hand, SK 827 increased IHb of the skin, dose-dependently and dilated cutaneous arterioles transiently with increased capillary red blood cell velocity. These findings suggest that the pharmacological effects of SK-827 on the microcirculation of the brain and the skin differ from each other due to the activity of the autoregulatory mechanism. PMID- 8364161 TI - Development and mitotic activity of the metrial gland in rat uterus during mid pregnancy. AB - Development and mitotic activity of metrial gland in rat uterus were investigated focusing on the point of implantation during mid-pregnancy. In decidua basalis, the granulated metrial gland (GMG) cells slightly increased in number during days 8-12 of pregnancy and then decreased, while the cells appearing in the mesometrial triangle on day 9 continued to increase until day 16, forming the metrial gland in situ. By contrast, the mitotic change in the mesometrial triangle was similar to that in the other 2 regions, decidua basalis and the inner layer of myometrium. In all 3 regions, mitotic rate rose drastically on day 9, and then gradually decreased until day 16. However, most of the mitotic cells lacked the PAS-positive cytoplasmic granules in any regions. Mitotic activity in GMG cells was very low and almost unchanged throughout the gland development. These results suggest that the rapid rise of mitotic rate is due to the active mitosis of PAS-negative cells, presumably GMG precursor cells, existing widely in the implantation point of rat uterus during the early development of the gland. Immunocytochemical study revealed that progesterone receptors were localized in decidual and muscle cells and fibroblasts, but not in GMG cells during the development of the gland. The present study suggests that the metrial gland cells are proliferated, differentiated and maintained by the progesterone-sensitive stromal cells, such as decidual cells and/or fibroblasts. PMID- 8364162 TI - No inhibitory effects of danazol estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins. AB - The effects of danazol on estrogen production by rat ovaries were investigated. Hypophysectomized immature female rats were injected daily with 2.5 or 5 IU of pregnant mare serum gonadotropin (PMS) and simultaneously daily given vehicle only or danazol (100 mg/kg body weight) for 14 days. Danazol did not decrease the activities of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, 17, 20 lyase and aromatase in the ovaries of rats stimulated by 5IU of PMS. Danazol also did not decrease the activities of 3 beta-hydroxysteroid dehydrogenase and aromatase, and the production of aromatizable androgens (androstenedione plus testosterone) from progesterone in the ovaries of rats stimulated by 2.5 IU of PMS. In accordance with these results, danazol did not reduce the level of estradiol-17 beta in the sera of rats stimulated by 2.5 and 5 IU of PMS. The present results suggest that danazol does not inhibit estrogen production by the rat ovary through its direct action on the ovary. PMID- 8364163 TI - The RBG-banded karyotype of Oryctolagus cuniculus at the 550-band stage. AB - Representative haploid RBG-banded karyotypes of Oryctolagus cuniculus and diagrammatic representation of the banding patterns at the 550 band stage are presented. PMID- 8364164 TI - Expression of proto-oncogenes and cytoskeletal actin gene in foreign body-induced murine sarcomas. AB - To investigate possible differences in the process of tumorigenesis induced by genotoxic and non-genotoxic agents, the expression of several oncogenes and cytoskeletal actin gene was examined in murine sarcomas induced by foreign body (plastics) and 3-methylcholanthrene treatments. RNAs isolated from the resultant tumors were analyzed by dot blot and Northern blot hybridization with various oncogene probes. Levels of expression of c-myc, c-Ha-ras, c-Ki-ras, c-N-ras c raf, c-src and cytoskeletal actin were similar and in distinguishable in both sarcoma groups. c-yes, c-erbB and c-sis transcripts were not detected in either. The single difference found was concerned with high levels of c-fos expression in fibrous capsules formed around the foreign body plastic material. Thus the pattern of expression of the above cellular genes was not specific and could not be used to distinguish sarcomas induced by non-genotoxic treatments from those caused by genotoxic exposure. PMID- 8364165 TI - Age-related changes in gonadotropin, prolactin and growth hormone levels with reference to the development of uterine adenomyosis in female SHN mice. AB - The patterns of serum FSH, LH, PRL and GH levels in SHN mice were determined by radioimmunoassay between 1 and 12 months of age. In addition, the incidence of spontaneous development of uterine adenomyosis and mammary tumor was also studied for 12 months. Serum FSH level increased gradually with age while the level of LH was almost constant during the observation period. On the other hand, concentrations of PRL and GH significantly increased with age. The present data showed that the development of adenomyosis and mammary tumor rapidly increased after 6 and 9 months of age, respectively. Pituitary grafting at 30 days of age resulted in a high incidence of adenomyosis after 6 months of age. There were no significant differences in FSH and LH levels between mice with and without pituitary grafting. However, pituitary grafting resulted in the increase in PRL and GH levels compared with age-matched controls. These findings altogether suggest that the spontaneous development of adenomyosis in SHN mice may be related to the elevation in PRL and GH levels as a function of age. PMID- 8364166 TI - Inhibition of rat mammary tumorigenesis by voluntary exercise. AB - In this study, the anti-promoting effect of voluntary (wheel) exercise on 7, 12 dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis was investigated. All rats were fed high fat diets (23% of calories as fat) to mimice the typical western diet. Two doses of DMBA were used to determine if the antipromoting effects of exercise were dependent on the strength of the initiating agent. In addition, tumor estrogen receptors were assayed to determined whether exercise, through an estrogen-suppressing mechanism, selects for estrogen receptor-negative tumors. Female Sprague-Dawley rats were fed a semi-purified 23% fat (corn oil) diet (AIN-76A) and, on day 50 of age administered DMBA by gavage at 5 or 10 mg/rat. Rats were then randomized into 4 groups (n = 30) as follows: 1) low DMBA/sedentary; 2) low DMBA/exercise; 3) high DMBA/-sedentary; and 4) high DMBA/exercise. Active rats were placed in wheel-cage units, which allowed voluntary access to an activity wheel for 133 (low DMBA) and 77 (high DMBA) days, respectively, Sedentary rats were placed in conventional cages. Both active groups exhibited significantly lower total tumor numbers than their sedentary controls: 75 vs 102 (low DMBA) (p < 0.05) and 90 vs 160 (high DMBA) (p < 0.001). Compared to sedentary controls, latency was significantly lengthened in the low but not the high DMBA active groups; multiplicity, in contrast, was significantly decreased in the high, but not the low DMBA exercised group. Exercise had no effect on overall tumor incidence. When segregated into exercise tertiles, total tumor active compared to the least active tertile, particularly in the high DMBA group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364167 TI - Opioid dependency and T-helper cell functions in rhesus monkey. AB - Administration of morphine sulfate to rhesus monkeys may activate the quiescent lymphocyte for proliferation, induce a transient increase in the T cell proliferative response to mitogens, and cause an enhanced interleukin-2 release from the mitogen-stimulated lymphocytes. However, longitudinal studies of the animals dependent upon morphine or L-a-acetyl-methadol, a long-acting opioid, revealed an overall immunosuppression of T helper functions. In vitro studies using morphine and its antagonist naloxone suggested that the immunosuppression was not a result of a direct interaction between the opioids and conventional opiate receptors which might have been present on the lymphocytes. The studies also showed the importance of measuring [3H]thymidine incorporation rather than its uptake into cells to assess T cell activation. PMID- 8364168 TI - Unusual behaviour of the LNCaP prostate tumour xenografted in nude mice. AB - The tumourigenicity of the LNCaP prostatic cell line was investigated in vivo after prostatic (orthotopic), subcutaneous (ectopic) and concomitant implantations in male Balb/c nude mice. Swollen lymph nodes were detected in the inguinal region only after subcutaneous implantation but could not be characterized by immunohistochemistry. However, when grafted to Endoxan pretreated mice, they generated well differentiated tumours which secreted prostate-specific acid phosphatase. A parallel study was conducted to investigate the metastatic potential of the LNCaP tumour using several routes of implantation (intravenous, bone contact, intrasplenic and intracranial). Tumours grew only after intracranial implantation. No production of either haematogenous or bony metastases was recorded. PMID- 8364169 TI - The acute toxicity and in vivo antitumour activity against L1210 leukemia of triphenyltin 3,5-diisopropylsalicylate, bis (di-n-butyl-(s)-2-pyrrolidone-5 carboxylato)tin oxide and di-n-butyltin bis(3-amino-4-methylbenzoate). AB - Triphenyltin 3,5-di-isopropylsalicylate, compound 1, is characterized by a maximum tolerated dose (MTD) of 20 mg/kg. Bis[di-n-butyl(2-pyrrolidone-5 carboxylato)tin] oxide, compound 2, and (di-n-butyltin bis(3-amino-4-methyl benzoate), compound 3, exhibit similar acute toxicities (MTD = 8 mg/kg) despite their lower in vitro activity, as compared to compound 1, against the two human tumor cell lines MCF-7 and WiDr. All three are inactive in vivo against L1210 leukemia in mice. PMID- 8364171 TI - Electron microscopic investigations of progressive early metastasis of cutaneous melanoma. AB - Primary metastasis of cutaneous malignant melanoma seems to occur especially via the initial lymphatics (IL). In samples of 50 melanomas examined by TEM melanoma cells (MCs), invading IL were demonstrated in 24 specimens. MCs were scarcely found in the immediate vicinity of blood vessels. After the MC has escaped from the MC-complex, connective tissue fibers and cells represent physiological guide ways that lead the MC to the IL. Located close to the IL, the MC develops pseudopodium-like cytoplasmic processes that penetrate the abluminal fibrous network, fuse partially with the endothelium and destroy it. It seems to be important that the melanomas invade IL as single cells and not in form of cell clusters. PMID- 8364170 TI - Effect of a biological response modifier, PSK, on intestinal flora of tumor bearing mice. AB - PSK, a protein-bound polysaccharide derived from basidiomycetes, is a biological response modifier that exhibits a variety of activities following oral administration, including prevention of infection. In this study, the effects of oral administration of this drug on microbial flora of tumor-bearing mice were examined. Numbers of Staphylococcus, Streptococcus and Pseudomonas were increased, and those of Bifidobacterium and Lactobacillus were reduced in fresh feces of mice from later than 9 weeks after inoculation of sarcoma 180. However, these changes were prevented by oral administration of PSK. In mice bearing sarcoma 180, the increases in numbers of Staphylococcus and Pseudomonas and the decrease in those of Bifidobacterium were further enhanced by intraperitoneal administration of anticancer agent mitomycin C, but such changes were suppressed by oral administration of PSK. These results suggest that PSK has a preventive effect against abnormal conditions of the intestinal flora induced by tumor inoculation or the administration of anticancer agents. PMID- 8364172 TI - Quality assurance: an Australian lawyer's perspective. PMID- 8364173 TI - Quality assurance in the United Kingdom. AB - In short, quality assurance in UK healthcare has developed since the mid-1980s driven by a series of national policy initiatives in the NHS, by increasing determination of the clinical professions to maintain standards, and by a general consumer movement to know more about public and professional services. Much has been achieved but there remains substantial debate about quality assurance leadership, coordination, funding and evaluation--or even what to call it. PMID- 8364174 TI - An investigation of awareness of antenatal protocols. AB - Previous audit at the Homerton Hospital had revealed a poor level of compliance with established antenatal protocols mandated by risk factors detected at the booking visit. Medical staff were questioned as to their awareness of five of the most important protocols and their response was analysed by a new scoring system. The scores were generally low though consultants scored more highly than junior staff. Scores were related to the length of obstetric experience and duration of work in the obstetric unit but were not related to frequency of the use of the protocol manual nor to the last time that reference was made to the manual. To improve compliance within the unit, the following recommendations were made: (1) regular revision of protocols to incorporate the current views of senior clinicians and (2) improved dissemination of information. The scoring system described here should prove to be a simple and effective method for the assessment of protocols within any unit. PMID- 8364175 TI - Emergency treatment of bronchospastic attacks in an emergency medicine department: effects of a quality improvement project. AB - New insights have recently changed the therapeutical approach to bronchospastic attack (BA). In this paper we present the results of a quality assurance study devised to: (1) verify the extent to which these new insights are put into practice in our Emergency Medicine Department (EMD); (2) evaluate changes in EMD medical staff behaviour faced with BA after discussion and distribution of medical practice guidelines on the treatment of BA (a document produced by a group of experts in pulmonary medicine working in the EMD on the basis of current literature and personal experiences); (3) assess the impact of such guidelines on quality care. A retrospective analysis demonstrated an incorrect treatment of BA in the EMD. After the introduction of the guidelines we observed: (1) an improvement in physician behaviour that completely agreed with guidelines in 56% of instances after discussion and distribution of the document, in 8% before; (2) an improvement in the outcome of patients treated for BA in the EMD (13 versus 36% relapses for patients treated in the EMD and discharged). PMID- 8364176 TI - Improving quality in emergency services to reduce hospital admission. AB - At the Emergency Department of Udine General Hospital (Italy) a programme to reduce admissions to the Internal Medicine Department was introduced in 1991. The majority of these admissions come from the Emergency Department, where many people, often without acute conditions, claim medical care. The programme consisted in organizational, professional and economic changes. At the end of 1991, the overall number of admissions to Udine General Hospital, as compared to 1990, decreased by 7.1%, but admissions to the Internal Medicine Department showed an 11.2% reduction. Finally, examinations for internal medical complaints in the emergency ward, not followed by hospitalization, increased by 15.5%. These results showed a reduction in admissions to the Internal Medicine Department greater than previously planned, with an increase in the number of outpatient examinations in the emergency room not followed by admission. Further targets were planned for 1992 to increase the quality of the service. PMID- 8364177 TI - Delivery of primary care in hospital and community settings in Australia. AB - This study examined the interface between emergency departments and community general practice in terms of their delivery of primary care services. Through the collection of casemix and treatment data, and interviews with patients, information was gathered relating to the extent of primary care delivery in emergency departments, problems managed and treatments provided in the two settings and patients' characteristics and reasons for choosing to seek primary care in the emergency department. The results indicate a high proportion of primary care delivery is in emergency departments, and that there is a need for delivery in this setting to continue. The results are discussed in terms of such quality assurance issues as monitoring primary care in emergency departments and addressing patient needs. PMID- 8364178 TI - Data comparability issues in international research and quality assurance. AB - Impediments to and progress toward valid and reliable international quality comparisons at the diagnosis or case type level are identified and discussed. The need for uniformity in each of the following is established: (1) international clinical data set, (2) definitions of clinical data elements and (3) data collection practices. The need to establish a clinically adequate international data base is discussed and action steps are identified. PMID- 8364179 TI - Adverse patient occurrences in a university hospital: a comparison of screening results registered by specialists and by external review. AB - A quality assurance system for generic screening of patient care has been developed in a university hospital in The Netherlands. This system is based on the Medical Management Analysis System, developed in the United States. Patient care is systematically screened for adverse patient occurrences (APOs). Screening criteria have been developed and some adjustments have been made to the original system, because of structural differences in health care between the United States and The Netherlands. The results of a study comparing two screening strategies are presented: screening by a medically trained, outside reviewer and screening by the Ear, Nose and Throat specialists themselves. The reviewer screened almost all admissions to the department as opposed to the specialist, who filled in screening forms of only 77.5% of the admissions. Specialists are found to register more APOs in their own domain (42%) as compared to the screener (28%). Issues concerning the nursing process receive less attention by the specialists (14%) than by the screener (22%). Because the personnel delivering direct patient care are more familiar with and informed about this process of care, the importance is stressed of getting specialists as well as nurses involved in the evaluation of the care they deliver to patients. PMID- 8364180 TI - Registration of adverse patient occurrences in a university hospital: relations between adverse patient occurrences and characteristics of hospitalized patients. AB - This paper reports the results of a survey on adverse patient occurrences (APOs) in patient care in a university hospital in The Netherlands. Screening for APOs is important as an instrument of quality assurance. Results from 1 year of screening have been related to specific patient characteristics. Age, length of stay and diagnosis group are strongly related to the identified APOs. The chances of APOs are very high if the patient belongs to certain diagnosis groups (operation procedure salivary gland, malignant disorder ear, nose, throat) and at the same time has a long length of stay in the hospital. The chances of being afflicted with more than one APO are strongly related to age and length of stay. With regard to the types of APO, this study shows a relation between patient characteristics and some APOs, but the statistical significance or the nature of these relations varies with type. PMID- 8364181 TI - Quality in alternative care. PMID- 8364182 TI - Quality of care in eastern Europe: the diagnosis is clear, the therapy not. PMID- 8364183 TI - Macrophage inflammatory protein: its characteristics, biological properties and role in the regulation of haemopoiesis. AB - Studies on haemopoietic stem cells had led to the realisation that negative feedback inhibitors play an important role in regulating their proliferation. One such molecule was identified as MIP-1 alpha. One of a family of cytokines, originally recognised as inflammatory molecules, MIP-1 alpha is now potentially valuable as a means of manipulating and protecting haemopoietic (and possibly other) stem cells during chemotherapy. This short review briefly considers the structural classification of MIP-1 alpha and its molecular relatives and indicates some of the probable human/murine equivalent molecules outlining the evidence for the equivalence of MIP-1 alpha (murine) and LD78 (human). Sources of MIP-1 alpha/LD78 are identified as monocyte/macrophage and lymphocytic cells and their role in inflammatory responses is seen to be significant. All proliferation in haemopoietic tissue is now recognised as a major target for MIP-1 alpha action. In vitro it synergises with certain growth factors to promote progenitor cell colony formation, but effects are dependent on the maturational age of the cells promoted. With more primitive cells it is seen as inhibitory. This property is particularly valuable in vivo where MIP-1 alpha can protect stem cells against the effects of cytotoxic agents. Since it appears that leukaemic stem cell proliferation is not inhibited, MIP-1 alpha/LD78 present great potential for stem cell protection in the theatre of cytotoxic therapies. PMID- 8364184 TI - Regional distributions of beta-thalassemia mutations in Turkey. AB - The distributions of twelve beta-thalassemic mutations in samples (n = 139 chromosomal samples) from four regions of Turkey were determined. The frequencies of these mutations did not reveal a notable region specific heterogeneity. In particular, the four mutations, IVS.1/nt.110(G/A), IVS.1/nt.6(T/C), IVS.1/nt.1(G/A) and nonsense codon.39(C/T), with country-scale frequencies of 35.9%, 21.6%, 13.0% and 7.2%, respectively, were found to be distributed with rather similar frequencies also on a regional scale. PMID- 8364185 TI - Flow cytometric determination of active oxygen (hydroperoxide) produced by peripheral blood neutrophils in patients with hematological disorders. AB - We analyzed active oxygen (hydroperoxide; H2O2) production by peripheral neutrophils in various hematological diseases by flow cytometry. One hundred microliters of heparinized fresh blood was sequentially incubated at 37 degrees C with 2',7'-dichlorofluorescein diacetate and with or without phorbol myristate acetate (PMA). After hemolysis, the pelleted white blood cells were subjected to flow cytometry, and the neutrophil fraction was gated on the cytogram. Production of H2O2 by the fraction was estimated by determining the increase in the relative intensity of fluorescence emitted from the fraction in response to stimulation by PMA. In controlled chronic myelogenous leukemia (CML) (WBC < 1 x 10(10)/1), H2O2 production was normal, while in uncontrolled CML (WBC > or = 1 x 10(10)/1), it was reduced. In myelodysplastic syndrome (MDS), H2O2 production was also reduced, but no significant difference was observed among FAB classification disease types in MDS patients. In untreated acute non-lymphocytic leukemia (ANLL), H2O2 production was reduced, while in the complete remission stage of ANLL, its level was normal, suggesting recovery from normal clones. In aplastic anemia, the H2O2 production level was normal. Steroid therapy might be responsible for the reduction of H2O2 production in non-Hodgkin's lymphoma and multiple myeloma. The production of H2O2 is closely related to the oxygen-dependent bactericidal activity of neutrophils, and, hence, can be utilized as an index to indicate susceptibility to infection. This neutrophil function can be determined easily in ordinary clinical facilities by using flow cytometry, and care should be taken to prevent infection when H2O2 production is reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364186 TI - Disappearance of Ph1 chromosome with intensive chemotherapy and detection of minimal residual disease by polymerase chain reaction in a patient with blast crisis of chronic myelogenous leukemia. AB - We diagnosed a patient with chronic myelogenous leukemia (CML) in chronic phase (CP) on the basis of clinical findings, Ph1 chromosome detected by cytogenetic analysis, and bcr-abl fusion mRNA detected by reverse transcriptase-dependent polymerase chain reaction (RT-PCR). One month after diagnosis, the patient developed extramedullary blast crisis in the lymph nodes, and then medullary blast crisis in the bone marrow, in which different surface markers were shown. Combination chemotherapy with BH-AC, VP16, and mitoxantrone was administered; this resulted in rapid disappearance of the lymphadenopathy, restoration of normal hematopoiesis, and no Ph1 chromosome being detected by cytogenetic analysis. RT-PCR performed to detect the residual Ph1 clone revealed that although the Ph1 clone was preferentially suppressed, it was still residual. The intensive chemotherapy regimen preferentially suppressed the Ph1-positive clone and led to both clinical and cytogenetic remission in this patient with BC of CML; we suggest that RT-PCR is a sensitive and useful method for detecting minimal residual disease during the clinical course of this disease. PMID- 8364187 TI - Primary pulmonary non-Hodgkin's lymphoma in a Japanese renal transplant recipient. AB - Pulmonary non-Hodgkin's lymphoma (NHL) developed in a 31-year-old renal transplant recipient 3 years after transplantation. Chest roentgenogram showed rapidly progressive multiple nodules in both lungs. The pleural fluid obtained by needle aspiration contained many atypical cells with surface B cell antigen and abnormal karyotype. The patient died of pulmonary edema shortly after combination chemotherapy was begun without regression of the tumors. Autopsy revealed diffuse large cell NHL confined to both lungs. Immunological examination and DNA analysis of the tumor showed monoclonal B cell NHL. PMID- 8364188 TI - Autoimmune hemolytic anemia after Kawasaki disease in a child. AB - A 2-year-old male presented with upper respiratory tract infection symptoms, continuous high fever, extensive truncal rash with desquamation, lymphadenopathy, subconjunctival hemorrhage, and oral stomatitis. He was diagnosed with Kawasaki disease and did well on aspirin. Approximately 8 weeks after initial presentation he had evidence of severe immune hemolysis. At that time a direct antiglobulin test was microscopically positive; it became strongly positive (3 + IgG, w + C3) 2 weeks later. The serology was unusual in that a warm IgG autoantibody and a low titer high thermal range cold antibody of unusual specificity (anti-Ena or anti Pr) were present. We were uncertain as to which antibody caused the hemolysis, or whether they worked synergistically. The hemolysis resolved following treatment with high dose prednisone. PMID- 8364189 TI - CD33, CD4-double positive blastic transformation in a patient with chronic myelogenous leukemia. AB - We report a 19-year-old female with blastic transformation of chronic myelogenous leukemia whose blasts had CD33 and CD4 phenotypes, although no significant characteristics were detected by morphological and histochemical analysis. In a colony assay with hematopoietic growth factors, the blasts proliferated and differentiated into myelo-monocytic lineage, particularly in the presence of GM CSF or IL-3 + G-CSF. The blasts transformed from CML were assumed to be myelo monocytic progenitor cells, corresponding to GM colonies. Blastic transformation expressing such a phenotype has not been reported previously. PMID- 8364190 TI - Gamma/delta T-cell lymphoma with hepatosplenomegaly: report of a case. AB - We describe the case of a patient with peripheral gamma/delta T-cell lymphoma (T ML) with hepatosplenomegaly, generalized lymphadenopathy, and bone marrow involvement. A 44-year-old man had lymphoma, which became clinically apparent 2 months after the onset of myositis and insulin-dependent diabetes mellitus. A cervical lymph node biopsy specimen showed diffuse infiltration by large neoplastic cells with vascular proliferation. The neoplastic cells expressed the T-cell receptor (TCR)delta chain detected by TCR delta 1 and delta-TCS1, CD3, CD30, CD45RO, and epithelial membrane antigen, but not the TCR beta chain detected by beta F1, CD1a, CD2, CD4, CD5, CD7, CD8, CD25, HLA-DR, and terminal deoxynucleotidyl transferase. The cells had a clonal rearrangement of TCR gamma chain gene and a germ-line configuration of immunoglobulin heavy chain gene and TCR beta chain gene. Despite chemotherapy, the patient died of refractory lymphoma 4 months after diagnosis. Examination at autopsy revealed that the main hepatic and splenic neoplastic infiltration sites were the portal area and white pulp, respectively. Our patient differed from those with gamma/delta T-ML with hepatosplenic involvement reported previously with respect to the hepatic and splenic neoplastic infiltration patterns and the presence of lymphadenopathy. PMID- 8364191 TI - Workshop on organization and methods in diagnostic haematology, Bad Homburg, 9-11 October 1992. PMID- 8364192 TI - Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin's disease and non-Hodgkin's lymphomas. PMID- 8364193 TI - Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase. AB - Recent clinical data have shown that enzyme replacement therapy with macrophage targeted glucocerebrosidase (GCR) can be effective in treating type 1 Gaucher disease. Sera from 262 patients, repeatedly infused with GCR, were assessed for the presence of antibodies to this therapeutic protein. Patient serum samples obtained at 3-month intervals were assessed by enzyme-linked immunosorbent assay and those with values greater than two standard deviations above the mean value obtained with a pool of normal human sera were further characterized by radioimmunoprecipitation. At the time of these analyses, the duration of patient treatment varied from 3 months to approximately 3 years. Of the 262 patients analyzed, 34 (12.9%) showed IgG antibodies, as confirmed by radioimmunoprecipitation. All patients who seroconverted did so within 1 year of treatment. The predominant antibody developed was the IgG1 subclass. Fourteen patients in the study experienced periodic symptoms suggestive of immediate hypersensitivity. Nine of these 14 patients had antibody to GCR as determined by radioimmunoprecipitation, whereas 5 patients were antibody negative. There was no evidence of the development of IgE antibodies in these 14 patients. The presence of GCR antibodies did not appear to effect efficacy of therapy in any of the patients treated to date. PMID- 8364194 TI - Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high dose intravenous immunoglobulin. AB - Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated. PMID- 8364195 TI - Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony-stimulating factor. AB - Mortality of bone marrow transplant (BMT) patients who develop invasive fungal infection is greater than 80%. Long-term follow-up of 46 consecutive BMT patients who received recombinant human macrophage colony-stimulating factor (rhM-CSF) as adjunctive therapy with standard antifungal treatment who were entered into phase I/II trials at The Fred Hutchinson Cancer Research Center is reported. rhM-CSF (100 micrograms/m2 to 2,000 micrograms/m2; Chiron/Cetus Corporation, Emeryville, CA) was administered from day 0 to 28 after determination of progressive fungal disease. Results of long-term follow-up of fungal infection, relapse, and survival were compared with 58 similar historical controls. Multivariable analysis of the patients who received rhM-CSF showed two factors that significantly correlated with poor survival: Karnofsky score < or = 20% and Aspergillus infection. Overall, survival of patients who received rhM-CSF was greater than that of historical patients (27% v 5%) and was entirely because of a 50% survival rate in patients with Candida infection and Karnofsky scores greater than 20%. Prospective, randomized, controlled trials to determine efficiency of rhM-CSF are indicated and should be directed at patients with invasive candidiasis. PMID- 8364196 TI - A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells. AB - The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37-Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells. PMID- 8364197 TI - Generation of natural killer cells from both Fc gamma RII/III+ and Fc gamma RII/III- murine fetal liver progenitors. AB - In vitro culture of day-15.5 murine fetal liver (FL) cells in the presence of recombinant interleukin-2 (IL-2) results in the expansion of Fc gamma RII/III+ CD3-Ti-NK1.1+ cells displaying both natural killer (NK) and antibody-dependent cell cytotoxicity (ADCC) cytolytic activities. These FL-derived NK cells express Fc gamma RIII (CD16) in association with an Fc epsilon RI gamma homodimer on their surface. In contrast, in vitro expansion of FL cells in the absence of IL-2 generates noncytotoxic cells belonging to the myelomonocytic lineage (Mac1+Gr1+NK1.1-). Hence, IL-2 appears to be critical for the proliferation and differentiation of NK cells from FL progenitors. Experiments in which FL cells were fractionated by density gradient centrifugation before in vitro expansion showed that NK progenitors are contained within a cell population with a density of 1.04 < d < 1.08 g/mL. Cells with d > 1.08 g/mL (representing > or = 40% of FL cells) have no such NK progenitor activity. In addition, after intrathymic injection into Ly5 congenic host animals, day-15.5 CD4-CD8- FL cells mature into CD4+CD8+ thymocytes within 12 days. Interestingly, this T-cell progenitor activity is restricted to subpopulations of FL cells that also contain NK progenitors, but is absent in high-density (d > 1.08 g/mL) FL cells. Finally, fractionation of FL cells according to surface expression of Fc gamma RII/III complexes shows that NK (and T-lymphocyte) progenitors are found in both Fc gamma RII/III+ and Fc gamma RII/III-FL subpopulations. PMID- 8364198 TI - Rescue of W-associated mast cell defects in W/Wv bone marrow cells by ectopic expression of normal and mutant epidermal growth factor receptors. AB - The normal human epidermal growth factor receptor (EGF-R) (HERc), a chimeric EGF R/v-erbB (HERerbB) receptor, and the ligand-independent oncogenic EGF-R variant (v-erbB) were used to correct the mast cell defects in W/Wv bone marrow (BM) cells. In culture, all three receptor molecules transduced functional mitogenic signals in infected interleukin-3 (IL-3)-dependent bone marrow-derived mast cells (BMMCs) and enabled their differentiation into safranin-positive mast cells resembling connective tissue-type mast cells (CTMCs). Furthermore, expression of these receptors restored the capacity of W/Wv BMMCs to colonize the peritoneal cavity of mast cell-deficient W/Wv mice where they differentiated to safranin positive cells with similar frequencies as wild-type BMMCs. These experiments show that expression of normal and mutant EGF-Rs in W/Wv BM cells is able to complement the function of the c-kit-encoded Steel factor receptor (SLF-R) in mast cell development. We conclude that signal transduction by normal and mutant EGF-Rs in murine hematopoietic cells apparently involves components also used by the SLF-R, which suggests that these receptors use overlapping pathways for signal transduction. PMID- 8364200 TI - Role of stromal cells and macrophages in fibronectin biosynthesis and matrix assembly in human long-term marrow cultures. AB - Fibronectin is a major component of the extracellular matrix of adherent layers of human long-term marrow cultures where it may stabilize the extracellular matrix network and provide adhesion sites for primitive hemopoietic cells. This study was devised to analyze the role of adherent cell populations in fibronectin synthesis, matrix assembly, and degradation. In cultures performed under the conditions described by Gartner and Kaplan, immunoprecipitation after metabolic labeling showed that adherent cells synthesized a fibronectin variant comprising the EDa domain and lacking the EDb one. Vascular smooth muscle-like stromal cells were the cell subset responsible for this synthesis. Once synthesized by stromal cells, EDa+fibronectin was secreted into the supernatant and incorporated into the extracellular matrix. The cumulation in the extracellular matrix was predominant by weeks 5 and 6 of culture, when a decrease in the stromal cell intracytoplasmic content of fibronectin was observed. Stromal cells from a transformed cell line, L2Ori-, were also able to synthesize the EDa+fibronectin variant, although for these cells the assembly into the extracellular matrix was partly impaired. Besides stromal cells, other cell types participated in fibronectin synthesis: early-adhering granulomonocytic cells and macrophages appearing later in culture were able to synthesize an EDa-, EDb- fibronectin variant, clearly distinct from the EDa+ variant produced by stromal cells. Studies on cultures in which macrophage growth was stimulated at the expense of stromal cells by adding granulocyte-macrophage colony-stimulating factor (50 ng/mL) to the culture medium showed a striking decrease in amounts of fibronectin measured in the adherent layer. This decrease was caused by a lack of incorporation of fibronectin in the extracellular matrix, disclosing a major difference between stromal cells and macrophages in terms of matrix assembly. This study confirms the similarity between stromal cells and vascular smooth muscle cells, because in vivo subendothelial intimal aortic smooth muscle cells and cultured smooth muscle cells from the aortic media express the EDa+, EDb- fibronectin variant. Furthermore, our results suggest that the level of fibronectin in adherent layers is regulated by stromal cells and macrophages. The balance between these two cell populations may therefore be crucial for the local control of hemopoiesis by regulating the extracellular fibronectin available for the adhesion of hematopoietic cells. Our data indicate that it may be essential to study the adhesion of stem cells to EDa+, EDb- fibronectin instead of EDa-, EDb- soluble fibronectin, as found in human plasma. PMID- 8364199 TI - Relative contributions of human types 1 and 2 T-helper cell-derived eosinophilotrophic cytokines to development of eosinophilia. AB - The relative contributions of type 1 and 2 T-helper (Th1 and Th2) cell-derived interleukin (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 were studied in the regulation of sequential events in the development of eosinophilia. Using eosinophils from normal donors and neutralizing antibodies that selectively block cytokine activities, we analyzed the effects of these cytokines in supernatants (SN) of well-characterized allergen-specific Th2 and Th1 T-lymphocyte clones (TLC) generated from atopic and nonatopic individuals, respectively. Eosinophil colony formation from CD34+ bone marrow progenitor cells in semisolid cultures could be induced both by Th1 and Th2 SN, mainly mediated by the synergistic effects of GM-CSF and IL-3, whereas IL-5 had only a minor additive effect. High production of mature eosinophils in liquid cultures of unseparated mononuclear bone marrow cells could only be induced by Th2 SN, which could be more than 90% blocked by anti-IL-5, but not by anti-IL-3 or anti-GM-CSF. Chemotaxis of mature peripheral blood eosinophils could equally well be induced by Th1 and Th2 SN, although the relative contribution of the individual cytokines was clearly different in the two sets of SN. Priming of platelet-activating factor (PAF) release by peripheral blood eosinophils was regulated by additive effects of the three cytokines and was stronger induced by the Th2 SN than by the Th1 SN. The present results indicate that IL-5, GM-CSF, and IL-3 control eosinophils throughout the course of development of eosinophilia, having different individual contributions in different compartments. The apparent strong and selective IL-5-dependence of certain yet undefined steps in eosinophil production in the bone marrow supports the concept of the generally assumed causal relation between predominant activation of IL-5-producing Th2 cells in response to allergens and development of eosinophilia in atopic disease. PMID- 8364201 TI - Erythropoietin structure-function relationships: high degree of sequence homology among mammals. AB - To investigate structure-function relationships of erythropoietin (Epo), we have obtained cDNA sequences that encode the mature Epo protein of a variety of mammals. A first set of primers, corresponding to conserved nucleotide sequences between mouse and human DNAs, allowed us to amplify by polymerase chain reaction (PCR) intron 1/exon 2 fragments from genomic DNA of the hamster, cat, lion, dog, horse, sheep, dolphin, and pig. Sequencing of these fragments permitted the design of a second generation of species-specific primers. RNA was prepared from anemic kidneys and reverse-transcribed. Using our battery of species-specific 5' primers, we were able to successfully PCR-amplify Epo cDNA from Rhesus monkey, rat, sheep, dog, cat, and pig. Deduced amino acid sequences of mature Epo proteins from these animals, in combination with known sequences for human, Cynomolgus monkey, and mouse, showed a high degree of homology, which explains the biologic and immunological cross-reactivity that has been observed in a number of species. Human Epo is 91% identical to monkey Epo, 85% to cat and dog Epo, and 80% to 82% to pig, sheep, mouse, and rat Epos. There was full conservation of (1) the disulfide bridge linking the NH2 and COOH termini; (2) N glycosylation sites; and (3) predicted amphipathic alpha-helices. In contrast, the short disulfide bridge (C29/C33 in humans) is not invariant. Cys33 was replaced by a Pro in rodents. Most of the amino acid replacements were conservative. The C-terminal part of the loop between the C and D helices showed the most variation, with several amino acid substitutions, deletions, and/or insertions. Calculations of maximum parsimony for intron 1/exon 2 sequences as well as coding sequences enabled the construction of cladograms that are in good agreement with known phylogenetic relationships. PMID- 8364202 TI - Evidence for a second type of fibril branch point in fibrin polymer networks, the trimolecular junction. AB - Fibrin molecules polymerize to double-stranded fibrils by intermolecular end-to middle domain pairing of complementary polymerization sites, accompanied by fibril branching to form a clot network. Mass/length measurements on scanning transmission electron microscopic images of fibrils comprising branch points showed two types of junctions. Tetramolecular junctions occur when two fibrils converge, creating a third branch with twice the mass/length of its constituents. Newly recognized trimolecular junctions have three fibril branches of equal mass/length, and occur when an extraneous fibrin molecule initiates branching in a propagating fibril by bridging across two unpaired complementary polymerization sites. When trimolecular junctions predominate, clots exhibit nearly perfect elasticity. PMID- 8364203 TI - Oxidative inactivation of plasmin and other serine proteases by copper and ascorbate. AB - Fibrin thrombi form at sites of injury, where leukocytes release a variety of oxidants. To determine whether oxidants might affect proteins of the fibrinolytic system, we examined the effects of various oxidants on plasmin. Plasmin was not inhibited by micromolar concentrations of hypochlorous acid, chloramine T, or H2O2. Neither Fe nor Cu affected plasmin alone or in the presence of H2O2. However, incubation of plasmin with 5 mumol/L Cu(I or II) in the presence of the reducing agent ascorbic acid resulted in a loss of its hydrolytic activity towards proteins as well as towards small synthetic substrates. The addition of EDTA, but not mannitol, prevented its inactivation. Inactivation was prevented by the addition of catalase and accelerated by hydrogen peroxide. Preincubation of plasmin with the competitive inhibitor alpha-N-acetyl-L-lysine methyl ester prevented inactivation by Cu(II) and ascorbate. These results together suggest site-specific oxidation of plasmin's active site. Treatment of the plasminogen activators tissue plasminogen activator and two-chain urokinase-type plasminogen activator, as well as trypsin, neutrophil elastase, and thrombin with Cu(II) and ascorbate resulted in a loss of their amidolytic and proteolytic activity, indicating the general susceptibility of serine proteases to this type of oxidation. Oxidation of the zymogens Glu-plasminogen and single-chain urokinase type plasminogen activator by Cu(II) and ascorbate resulted in the failure of these molecules to generate active enzymes when treated with plasminogen activators or plasmin, respectively. The active site His residue may be the target of oxidative inactivation, as evidenced by the partial protection afforded plasmin by the addition of Zn(II), histidine, or the platinum derivative, platinum(II) (2,2':6',2"-terpyridine) chloride. Because platelets contain micromolar concentrations of Cu and leukocytes are rich in ascorbate, Cu dependent site-specific oxidation might play a role in modulating proteolytic events and the life span of thrombi formed at sites of tissue injury. PMID- 8364204 TI - Persistent expansions of CD4+ CD8+ peripheral blood T cells. AB - CD4+ CD8+ cells are present during T cell differentiation in the thymus. Less than 2% of normal T cells that coexpress CD4 and CD8 also are released in the circulation and are present in the peripheral blood. In this study, nine individuals are described that manifested persistent expansions (11% to 43%) of circulating CD4+ CD8+ T cells that in three cases had large granular lymphocyte (LGL) morphology in the absence of either lymphocytosis or overt lymphoproliferative disorders. Southern blot hybridization of enriched CD4+ CD8+ cells with T-cell receptor beta (TCR beta) and TCR gamma probes showed that most cases had the 12-kb Eco RI germinal band deleted or of decreased intensity. In several individuals new TCR beta-specific bands of different intensity and distinct from case to case suggested either monoclonal or oligoclonal and polyclonal expansions. Immunophenotypic analysis showed that in 7 out of 9 cases the CD4+ CD8+ T cells presented with CD8 dim expression. Furthermore, all the CD4+ CD8+ cells did not express many of the known activation antigens (low or absent CD25, CD38, CD71, HLA-DR), whereas they expressed high levels of CD2, CD29, CD56, and CD57. In addition, the CD4+ CD8+ cells of 5 out of 9 subjects coexpressed CD45RA and CD45RO suggesting that these cells might be "frozen" in an intermediate state between naive and memory T cells. In conclusion, the present CD4+ CD8+ cases fall within a larger spectrum of disorders ranging from apparently normal to reactive or proliferative situations and encompassing cells with LGL morphology or LGL-associated antigens expression either in the presence or in the absence of absolute lymphocytosis that deserve careful follow-up investigations. PMID- 8364205 TI - Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases. AB - Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL 2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation. PMID- 8364206 TI - Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q. AB - Signal transduction through the T-cell receptor and cytokine receptors on the surface of T lymphocytes occurs largely via tyrosine phosphorylation of intracellular substrates. Because neither the T-cell receptor nor cytokine receptors contain intrinsic kinase domains, signal transduction is thought to occur via association of these receptors with intracellular protein tyrosine kinases. Although several members of the SRC and SYK families of tyrosine kinases have been implicated in signal transduction in lymphocytes, it seems likely that additional tyrosine kinases involved in signal transduction remain to be identified. To identify unique T-cell tyrosine kinases, we used polymerase chain reaction-based cloning with degenerate oligonucleotides directed at highly conserved motifs of tyrosine kinase domains. We have cloned the complete cDNA for a unique human tyrosine kinase that is expressed mainly in T lymphocytes (EMT) and natural killer (NK) cells. The cDNA of EMT predicts an open reading frame of 1866 bp encoding a protein with a predicted size of 72 Kd, which is in keeping with its size on Western blotting. A single 6.2-kb EMT mRNA and 72-Kd protein were detected in T lymphocytes and NK-like cell lines, but were not detected in other cell lineages. EMT contains both SH2 and SH3 domains, as do many other intracellular kinases. EMT does not contain the N-terminal myristylation site or the negative regulatory tyrosine phosphorylation site in its carboxyterminus that are found in the SRC family of tyrosine kinases. EMT is related to the B-cell progenitor kinase (BPK), which has recently been implicated in X-linked hypogammaglobulinemia, to the TECI mammalian kinase, which has been implicated in liver neoplasia, to the more widely expressed TECII mammalian kinase, and to the Drosophila melanogaster Dsrc28 kinase. Sequence comparison suggests that EMT is likely the human homologue of a recently identified murine interleukin-2 (IL-2) inducible T cell kinase (ITK). However, unlike ITK, EMT message and protein levels do not vary markedly on stimulation of human IL-2-responsive T cells with IL-2. Taken together, it seems that EMT is a member of a new family of intracellular kinases that includes BPK, TECI, and TECII. EMT was localized to chromosome 5q31-32, a region that contains the genes for several growth factors and receptors as well as early activation genes, particularly those involved in the hematopoietic system. Furthermore, the 5q31-32 region is implicated in the genesis of the 5q- syndrome associated with myelodysplasia and development of leukemia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364208 TI - T-cell-rich B-cell lymphoma. AB - We analyzed 23 cases of T-cell-rich B-cell lymphomas (BCL) to determine if the clinical features are characteristic of a discrete entity. Cases encoded as T cell-rich BCL in the hematopathology archives of the University of Texas M.D. Anderson Cancer Center between 1988 and 1991 formed the basis of this study. At least 50% of the total population of cells were required to be of T-cell phenotype. Actually, all but one patient had more than 70% T cells in the total population. Sixty-five percent of all cases were referred with other diagnosis such as Hodgkin's mixed cellularity, peripheral T-cell lymphoma (PTCL), or diffuse mixed lymphoma, and had received therapy accordingly. With the exception of splenomegaly, which occurred in 35% of cases, the other clinical characteristics and the response to therapy did not indicate that this entity represents a distinct type of lymphoma. Ann Arbor stage I-II presentations were seen in 10 of 23 (43%) T-cell-rich BCLs. Serum lactate dehydrogenase (LDH) was elevated in eight of 19 patients. Age, sex, and beta 2-microglobulin were not significantly different from classical B-cell large cell lymphoma. The clinical presentation and clinical outcome of T-cell-rich BCL did not differ from that of common B-cell large cell lymphoma, except for the higher proportion of splenomegaly seen in patients with T-cell-rich BCL. The presence of the T-cell rich infiltrate varied: it frequently was not seen at relapse or at other sites of disease at presentation. It was thus considered an unstable parameter. The major importance of identifying this entity is to distinguish it pathologically from other disorders such as Hodgkin's disease and PTCL, which would be treated in a different manner. PMID- 8364207 TI - Lysis of human monocytic leukemia cells by extracellular adenosine triphosphate: mechanism and characterization of the adenosine triphosphate receptor. AB - The present study shows that extracellular adenosine triphosphate (ATP) has the capacity to mediate dose-dependent lysis of the monocytic leukemia cell line THP 1. The lysis, assessed by 51Cr release, was found to be selective for ATP, because adenosine diphosphate (ADP) or other nucleotides were less effective in their ability to lyse the cells. The amount of 51Cr released was particularly enhanced by the stimulation of the cells with 1,000 U/mL of interferon gamma (IFN gamma) for 3 days, and the sensitivity was time and dose dependent. Analysis of the mechanism of lysis indicated that the fully ionized form, ATP4-, mediated the lysis, because the addition of cation chelators or the absence of the divalent cations, Ca2+ and Mg2+, in the culture medium of a 6-hour 51Cr release assay increased the percent specific lysis. Therefore, the ATP receptors on THP-1 cells were classified as P2Z purinoceptors. Moreover, it is shown here that the Ca2+/calmodulin complex plays a role in the regulation of the lysis by extracellular ATP of THP-1 cells, because antagonists of this complex, such as trifluoperazine or KN-62, were found to inhibit the ATP-mediated cell lysis. PMID- 8364209 TI - Effects of agents that inhibit cellular iron incorporation on bladder cancer cell proliferation. AB - Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe-) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer. PMID- 8364210 TI - Long-term follow-up of residual disease in acute lymphoblastic leukemia patients in complete remission using clonogeneic IgH probes and the polymerase chain reaction. AB - We sequentially studied bone marrow (BM) samples of 25 patients in complete remission of an acute lymphoblastic leukemia (ALL) using a simplified polymerase chain reaction (PCR) strategy (direct use of the PCR product as a clonogenic probe recognizing rearranged Ig heavy chain sequences) as a first approach. BM aspirates were serially investigated after obtention of a complete response. When sensitivity was less than 1:10(4), the PCR fragment was sequenced and a specific oligonucleotide was synthetized and used as a probe (five cases). Cases in which minimal residual disease (MRD) became undetectable were cross-controlled using either TCR delta rearrangement or a specific translocation to circumvent the problem of false-negative results arising from clonal evolution. The median follow-up was 30 months (3 to 51 months). Within the first 3 months of complete remission, MRD was detectable in 22 of 23 investigated patients and remained so in 19 of 21 patients examined at 6 months, regardless of the long-term clinical outcome. In patients remaining in complete remission at 30 months or more, two patterns of MRD emerged during the follow-up. Either it continuously decreased to ultimately become undetectable (five patients) or remained detectable (five patients) with an increase after discontinuation of treatment in two. In the eight patients who relapsed, MRD persisted throughout the clinical course, and eventually increased 3 to 12 months before relapse was clinically detectable. In one case, clonal evolution of the VDJ heavy chain region was observed and recurrence of MRD shown by the use of TCR delta rearrangement as a control. We conclude that the use of this simplified methodology is a valuable tool for the follow-up of MRD in a majority of ALL patients, though in a few cases, sequencing needs to be performed to achieve a relevant sensitivity. The possibility of clonal evolution requires a cross-control of any sample becoming negative whatever the initial rearrangement used to generate a probe. In patients on therapy, sequential search for MRD seems to be a good tool for predicting the long-term outcome. In addition, patients remaining positive at the time treatment is discontinued or with a high tumor burden after a few months therapy may be at a higher risk of subsequent relapse, although a longer follow-up is needed to answer this question. PMID- 8364211 TI - Molecular analysis of VH and VL regions expressed in IgG-bearing chronic lymphocytic leukemia (CLL): further evidence that CLL is a heterogeneous group of tumors. AB - We report the heavy (H) and light (L) chain variable (V) region sequences of cDNAs encoding the Ig receptor of two cases of CD5+ IgG-bearing CLL P87 and P103. In both CLL cases the H chain was encoded by members of the VH3 gene family. The L chain expressed by P87 belonged to the V lambda IV subgroup, whereas P103 used a member of the V kappa III subgroup. The VH3.P87 gene differed by only three nucleotides from 38P1, a VH3 gene previously cloned from a fetal liver cDNA library. Nucleotide sequence analysis demonstrated that the V kappa III.P103 gene differed by seven nucleotides from its most homologous germline counterpart, the Humkv325 gene, a highly conserved gene frequently expressed in IgM-bearing CLL. The nucleotide sequences of VH3.P103 and V lambda IV.P87 could not be reliably matched with reported germline V genes. The analysis of multiple independently obtained VH and VL cDNA clones from each tumor showed a lack of intraclonal diversification. The data show that V regions expressed in isotype-switched CD5+ CLL may be either in/near germline configuration or somatically mutated. Furthermore, these tumors, like their IgM-bearing counterparts, do not seem to undergo intraclonal diversification. PMID- 8364212 TI - Neutrophils do not bind to or phagocytize human immune complexes formed with influenza virus. AB - Neutrophils appear to form the first line of defense against influenza virus, yet it is unclear how these leukocytes recognize influenza-infected cells. While demonstrating that neutrophils adhere specifically to the sialic acid-binding site on the hemagglutinin molecule (HA) on the surface of influenza-infected (WSN[H1N1]) epithelial cells and not to other viral or epithelial cell antigens, it was observed that human neutrophils do not recognize immune complexes formed with influenza virus. Intact antibodies (mouse monoclonal antibodies [MoAbs] IgG1 and IgG2b, human immune heat-inactivated serum [predominantly IgG1], and IgG purified from human immune serum) that block the sialic acid-binding site on HA significantly reduced (> 80%) neutrophil adherence to influenza-infected epithelial cells. Binding and phagocytosis of free influenza virions and neutrophil agglutination by influenza virus were completely prevented by these antibodies. Intact and F(ab')2 fragments of mouse MoAbs to other viral epitopes caused increased neutrophil adherence to infected cells. This binding was eliminated by F(ab'2) fragments of MoAbs against the sialic acid-binding site on HA, but not by saturating amounts of MoAbs, which block the neutrophil Fc receptors. Thus, it appears that human neutrophils show little ability to bind via their Fc receptors to the immune complexes formed with antibody and either influenza-infected epithelial cells or the free virion. These findings are in contrast to the general dogma, and are the first example of antibody opsonization reducing, rather than enhancing, neutrophil binding and phagocytosis of a pathogen. PMID- 8364213 TI - Analysis of delta-globin gene mutations in Greek cypriots. AB - We recently described four delta-globin gene mutations in Greek Cypriots studied by polymerase chain reaction (PCR) amplification and automated fluorescence-based DNA sequence analysis (Blood 78:3298, 1991). Selective restriction enzyme digestion of PCR products facilitated direct mutation detection. Twenty-eight additional samples from unrelated Cypriots with Hb A2 levels ranging from 0.6% to 3.6% were studied by PCR and showed the following: twelve had the delta 27 (ala- >ser) mutation, one was heterozygous for the delta IVS-2 AG-->GG change, and none had either the delta 116 (arg-->cys) or delta 141 (leu-->pro) mutations. The remaining samples were divided into two groups: 11 with borderline normal Hb A2 values that were not pursued; and four with abnormal Hb A2 values. The delta globin genes from these four samples were sequenced and the same four changes identified in each: a C-->T at -199, a C-->T at codon 4 (thr-->ile), a silent C- >T at codon 97, and an AT deletion at position 722 in IVS-2. The codon 4 change abolishes a Ple I site whereas the codon 97 creates an Nla III site, thus facilitating rapid identification. All four changes are in cis position, suggesting that the -199 C-->T, the C-->T at codon 97, and the AT deletion in IVS 2 are neutral polymorphisms present on the codon 4 (thr-->ile) chromosome. DNA haplotype analysis suggests all five delta-globin gene mutant alleles arose independently on different chromosomal backgrounds. PMID- 8364214 TI - Molecular basis of spectrin deficiency in hereditary pyropoikilocytosis. AB - Hereditary pyropoikilocytosis (HPP) is a recessively inherited hemolytic anemia characterized by severe poikilocytosis and red blood cell fragmentation. HPP red blood cells are partially deficient in spectrin and contain a mutant alpha or beta-spectrin that is defective in terms of spectrin self-association. Although the nature of the latter defect has been studied in considerable detail and many mutations of alpha-spectrin and beta spectrin have been identified, the molecular basis of spectrin deficiency is unknown. Here we report two mechanisms underlying spectrin deficiency in HPP. The first mechanism involves a thalassemia-like defect characterized by a reduced synthesis of alpha-spectrin as shown by studies involving synthesis of spectrin in two unrelated HPP probands and their parents: One parent carries the elliptocytogenic spectrin mutation, whereas the other parent is fully asymptomatic. Peripheral blood mononuclear cells as a source of erythroid burst-forming unit (BFUe) were cultured in a two-phase liquid culture system that gives rise to terminally differentiated erythroblasts. Pulse-labeling studies of an equal number of erythroblasts or morphologically identical maturity showed that the synthesis of alpha-spectrin as well as the mRNA levels as measured by the competitive polymerase chain reaction (PCR) method are markedly reduced in the presumed asymptomatic carriers and the HPP probands. In contrast, the synthesis and mRNA levels of beta-spectrin were normal. These results constitute a direct demonstration of an alpha-spectrin synthetic defect in a subset of asymptomatic carriers of HPP and HPP probands. The second mechanism underlying spectrin deficiency involves increased degradation of mutant spectrin before its assembly on the membrane. This is evidenced by pulse labeling studies of erythroblasts from a patient with HPP associated with a homozygous state for spectrin alpha I/46 mutation (leu-pro mutation at AA 207 of alpha-spectrin). These studies showed that although spectrin is synthesized in the cytosol in normal amounts, the rate of turnover of alpha-spectrin is faster resulting in about 40% to 50% reduced assembly of alpha-spectrin and beta-spectrin on the membrane. Thus, spectrin deficiency in this case is at least in part caused by increased susceptibility of the mutant spectrin to degradation before its assembly on the membrane. We conclude that at least two separate mechanisms underlie the molecular basis of spectrin deficiency in HPP. PMID- 8364215 TI - Elliptopoikilocytosis associated with the alpha 469 His-->Pro mutation in spectrin Barcelona (alpha I/50-46b). AB - We present two Spanish children with hereditary elliptopoikilocytosis. The mother displayed a symptomless elliptocytosis. Spectrin maps showed the alpha I/50-46b abnormality in the mother and in the children. The change was more conspicuous in the children than in the mother. The father carried the alpha V/41 allele, which is a common allele endowed with low expression. The alpha V/41 allele was also present in the children accounting for the much more severe expression of the alpha I/50-46b variant. The responsible mutation yielding the latter appeared to be the alpha 469 His-->Pro substitution (CAT-->CCT), which is a novel abnormality. The corresponding spectrin was designated spectrin Barcelona. As is often the case in hereditary elliptocytosis or poikilocytosis related to alpha spectrin variants, the change involved a helix 3; namely, helix 3 of repeating segment alpha 5. PMID- 8364217 TI - Rhesus D genotyping using polymerase chain reaction. PMID- 8364216 TI - Inhibition of factor VIIa/tissue factor by antithrombin III and tissue factor pathway inhibitor. PMID- 8364218 TI - Sulfamethoxazole-related antiplatelet antibody. PMID- 8364219 TI - Imprinting and loss of ABO antigens in leukemia. PMID- 8364220 TI - Expression of phospholamban mRNA during early avian muscle morphogenesis is distinct from that of alpha-actin. AB - We have studied the expression of phospholamban during the early development of chick embryos by in situ hybridization and have compared it to that of alpha cardiac and alpha-skeletal actin. In adult cross-striated muscles there is only one phospholamban gene and it is expressed exclusively in the heart and slow muscles. In the heart phospholamban transcripts were first detected at stage 14 in the region of presumptive ventricle and at stage 20 in the atrium. In the myotomal portion of the somites phospholamban mRNA was first detected at stage 20, which lagged behind the appearance of the alpha-actins. In the limb rudiments all three mRNAs were barely detectable through stage 24, but increased by stage 28+. However, quantitative analysis of signal intensity at stage 28+ indicated that less phospholamban mRNA is present in the limb bud than in the myotome since for phospholamban the ratio of the signal density in the myotome to that in the limb rudiments was about twice the value of the ratio determined for the alpha actins. Northern blot analysis of embryonic day 11 chick fast pectoralis muscle showed that phospholamban mRNA was not detected in vivo while alpha-cardiac actin mRNA was. Moreover, no phospholamban mRNA was detected in primary cultures derived from pectoralis muscle of the same age. In concert with previous observations that phospholamban is not detectable at stage 30-32 in wing or thigh muscle, these results suggest that phospholamban mRNA is expressed independently of the alpha-actins in the limb buds during early myogenesis. PMID- 8364221 TI - Differential expression of the two delta-crystallin genes in lens and non-lens tissues: shift favoring delta 2 expression from embryonic to adult chickens. AB - Chicken argininosuccinate lyase (ASL)/delta-crystallin, a lens enzyme-crystallin, is encoded in two linked genes (delta 1 and delta 2); only the delta 2 polypeptide contains ASL activity. Here we have quantified delta 1- and delta 2 crystallin mRNA in the lens, cornea, neural retina, heart, and brain at different stages of embryonic development and in 1-wk-old and 1-yr-old chickens by the polymerase chain reaction using internal delta 1 and delta 2 RNA standards. The delta 1/delta 2 mRNA ratio differed for every tissue and was regulated during development. In the embryo there was more delta 1 than delta 2 mRNA in the lens (50-100 times), cornea (3-4 times), and neural retina (2-20 times), about equal amounts of delta 1 and delta 2 mRNA in the heart, and more delta 2 mRNA in the brain (15 times). delta 1-Crystallin mRNA differentially decreased in every tissue after hatching; by contrast, the delta 2 mRNA remained about the same except for the lens, where it decreased 50-fold between 1 wk and 1 yr after hatching. In the 1-yr-old chicken, the delta 2/delta 1 mRNA ratios were 7 in the lens, 175 in the cornea, 22 in the neural retina, 107 in the heart, and 136 in the brain, indicating that delta 2-crystallin is strongly favored in all adult tissues of the chicken. The excess of delta 1 to delta 2 mRNA in the embryonic lens, cornea, and neural retina is intriguing, and suggests some connection with developing transparent eye tissues. Finally, we raise the possibility that expression of both delta-crystallin genes may create tetrameric ASL isoenzymes (perhaps with different specific activities). The unexpected predominance of delta 2 mRNA in the 1-yr-old lens suggests that both the enzymatic and refractive functions of ASL/delta-crystallin are operative and spatially separated, with the enzymatic role present in the cortical fibers and the refractive role in the center of the lens. PMID- 8364223 TI - Developmental regulation and cell type-specific expression of the murine gamma F crystallin gene is mediated through a lens-specific element containing the gamma F-1 binding site. AB - The mouse gamma F-crystallin gene, one of six differentially regulated members of the gamma-crystallin gene family, is expressed exclusively in central nuclear fiber cells of the adult lens. The expression of this gene is controlled through regulatory elements contained in two upstream enhancers and the proximal promoter. Here we show that while the upstream enhancers and the proximal promoter could each direct gene expression in fiber cells formed at early stages of lens growth and development, cooperation between these elements is required to achieve expression in fiber cells formed at later stages. Evidence is provided that cooperative interaction between these elements modulates gene expression by increasing promoter strength. We also show that sequences within the proximal promoter region that bind lens cell nuclear factor gamma F-1 are sufficient to elicit gene expression in central nuclear fiber cells of the adult lens. PMID- 8364222 TI - Molecular markers of differentiation in Caenorhabditis elegans obtained by promoter trapping. AB - Differentiation of specific cell types during animal development can be detected by monitoring expression of appropriate genes. For this study, six different beta galactosidase expression patterns which can be used as differentiation markers in the nematode Caenorhabditis elegans are described. An earlier promoter trap screen identified pools of recombinant plasmids which gave patterns of beta galactosidase expression when used to transform C. elegans. Each recombinant plasmid contained a random fragment of C. elegans genomic DNA fused upstream of a promoterless lacZ gene. Six of these pools were chosen, and individual pattern producing plasmids within these pools were identified. The expression patterns have been characterized more thoroughly than in the original screen, thereby providing molecular markers for differentiation of several cell types. Many of the expression patterns involve more than one cell type. The genomic origin of the inserts of active plasmids were determined through localization on the physical genome map. PMID- 8364224 TI - Evidence that the border of the neural plate may be positioned by the interaction between signals that induce ventral and dorsal mesoderm. AB - In the early Xenopus embryo, a quadrant of endodermal cells that have descended from the vegetal dorsal localization in the zygote produces signals that pass into the animal hemisphere and induce dorsal mesoderm from the marginal zone. From the remaining three quadrants of the bordering endoderm, signals pass into the animal hemisphere and induce ventral mesoderm in the marginal region. There is evidence that suggests that these same mesoderm-inducing signals continue through the plane of the tissue of the animal hemisphere where they may at least begin the processes of neural and epidermal induction by changing the competence of the prospective ectodermal cells, and possibly influencing the early regional biasing of later expression of at least some gene products, such as Epi-1 whose expression in the future epidermal domain seems specified before gastrulation. We hypothesized that the interaction of the ventral and dorsal signals within the plane of the tissue of the animal hemisphere may position the border of the neural plate. If this is so, then transplantation into the animal pole of cells that signal induction of ventral mesoderm should drive the neural plate boundary back toward the blastopore and shorten the anterior-posterior axis. Removal of cells that induce ventral mesoderm should result in an axis that is longer than normal. Results of our experiments support these predictions. Also, by late pregastrula stage 9, increasing the ventral signals has no effect. Thus the evidence suggests that the position of the anterior neural plate boundary is established before gastrulation begins by the interaction of the signals that induce the ventral and dorsal mesoderm. PMID- 8364226 TI - The expression of xenobiotic-metabolizing cytochromes P450 in fetal tissues. PMID- 8364225 TI - gli, a zinc finger transcription factor and oncogene, is expressed during normal mouse development. AB - The oncogene GLI is amplified and expressed in some cases of human malignant glioma and undifferentiated childhood sarcoma and is the prototype for a gene family characterized by a highly conserved set of five tandem zinc fingers and a consensus cysteine-histidine link. This zinc finger motif has been shown to bind DNA with sequence specificity and may mediate transcriptional regulation. Since GLI is expressed in embryonal carcinoma cell lines but not in most normal adult tissues and shows significant sequence similarity within its zinc finger domain to cubitus interruptus dominant (ciD), a Drosophila segmentation gene known to be important in the morphogenesis of the posterior portion of each larval segment, we established the temporal and tissue expression patterns of the mouse homologue of human GLI in day 10 through 18 mouse embryos with Northern blotting, reverse transcriptase coupled PCR, and in situ hybridization. gli transcripts were demonstrated on days 10 through 18 of mouse embryonic development as well as in normal adult uterus, brain, testis, and limb. Tissue expression of gli during gestation was demonstrated in Meckel's precartilage mesenchyme, the basis occipitus, rib mesenchymal condensations, primordial vertebral bodies, digital mesenchymal condensations in forefoot and hindfoot plates, the ependymal layer of the spinal cord, and the mesoderm of the gastrointestinal tract. Expression persisted throughout gestation in developing bone and cartilage of the extremities, the ribs, and the vertebral bodies, as well as the gastrointestinal tract mesoderm. These findings support a role for gli family genes in normal craniofacial and digital development in mammals first suggested by the demonstration of translocation breakpoints within the GLI3 gene in families with the Greig cephalopolysyndactylyl syndrome and subsequently by reduced gli3 expression in the mouse mutant extra toes. It is surprising that a single gene would be expressed in such a wide range of mesenchymal structures. PMID- 8364228 TI - Use of a polypropylene mesh in fixing a chronic intracerebroventricular cannula. AB - Surgical implantation of an intracerebroventricular cannula allows investigators to determine the effects of central administration of compounds on physiological/pathological events taking place in the periphery. Attempts to examine the influence of repeated, chronic drug administration on gastrointestinal function have been hampered by the tendency of cannulae to become dislodged and lost during the course of such studies. We describe herein the insertion of surgical polypropylene mesh between the skull and the fixative during surgical implantation of an intracerebroventricular (i.c.v.) cannula. This inexpensive addition to a standard surgical procedure extends the period of time during which the cannula remains viable for i.c.v. drug administration. Extending the active life of the cannula, in turn, allows the investigator to reduce the number of animals used. PMID- 8364227 TI - A method for the study of swimming stress and stress-induced antinociception in preweanling rats. AB - Stress-induced antinociception (SIA) which is well characterized in the adult rat can also be observed in young rats, and, by varying swimming times, it can be dissociated into opioid and nonopioid forms. However, swimming ability in the rat does not fully develop until the third postnatal week and this has precluded the study of swim SIA in neonates. We report here the development of a harness device to aid swimming in young rats which we have successfully employed down to the age of 2 days without distress to the animals. Further we have also shown the development of the opioid form of swim SIA in the rat using this device. Swim SIA is absent at days 2 and 5, but at postnatal day 10 a small level of SIA is evident which is reversed by naloxone (10 mg/kg). Swim SIA develops rapidly thereafter, and the adult profile is observed by day 25. PMID- 8364229 TI - Endothelium inactivation in in vitro perfused vascular beds. Comparison of methods. AB - In order to choose the best procedure to inactive the endothelium from vascular beds perfused in vitro, we compared four methods: perfusion with sodium deoxycholate 0.3% for 30 sec; 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate 0.3% (CHAPS) for 2.5 min; collagenase 0.2% for 15 min, and distilled water for 10 min, using the mesenteric arterial bed (MAB) of the rat. The effectiveness of the treatments used to inactivate the endothelium was assessed functionally by using acetylcholine and sodium nitroprusside and histologically using light microscopy. Phenylephrine was used to test the contractile properties of the preparations after each treatment. After collagenase, distilled water, and CHAPS treatment, a potentiated response to phenylephrine was observed, whereas sodium deoxycholate treatment did not modify phenylephrine-induced responses. Acetylcholine-induced responses were reduced by collagenase (60% reduction), CHAPS (30% reduction), and distilled water (52% reduction) treatment, and sodium deoxycholate completely abolished acetylcholine-induced responses. Except after collagenase treatment, smooth muscle relaxant responses were not altered. Medial smooth muscle cells displayed an unchanged morphology, appearing similar to those in control mesenteric arterial beds, except for collagenase and distilled water. Despite the fact that sodium deoxycholate treatment completely abolished acetylcholine-induced response, endothelial cells were still found. No treatment totally removed endothelial cells. In conclusion, we suggest that sodium deoxycholate treatment is the best procedure to inactivate endothelial cells from vascular beds perfused in vitro since it completely abolished endothelium dependent relaxation and did not interfere with smooth muscle vasodilating and contracting properties. PMID- 8364230 TI - A simple and reproducible cerebral thrombosis model in rats induced by a photochemical reaction and the effect of a plasminogen-plasminogen activator chimera in this model. AB - In this study a new model of cerebral ischemia, based on a middle cerebral artery (MCA) thrombosis in rats is described. Furthermore, the effect of the novel plasminogen activator (SUN9216), a plasminogen-plasminogen activator chimera, comprising the fibrin kringle 1 domain of a plasminogen, and the two kringles, and the serine protease domains of wild-type tissue plasminogen activator (t-PA), including a modification of the mannose glycosylation site on the kringle 1 of t PA (PK1de1FE1X), was studied in this model. In the newly described model of thrombotic cerebral ischemia, an occlusive thrombus occurred usually within 8 min in the MCA as a consequence of an endothelial injury subsequent to a photochemical reaction between a systemically administered photosensitive dye (rose bengal) and a transillumination of the MCA with a high-intensity green light with a wavelength of 540 nm. The study was quantitated by means of pathological examination of the MCA and the brain. A platelet-rich thrombus was observed in the MCA using electron microscopical analysis based on ion beam bombardment. At 24 hr after induction of the thrombus, the brain was removed from 13 control animals, nine coronal sections were stained from each brain with triphenyltetrazoliumchloride (TTC), and the ischemic area was quantitated. A constant area of infarction was observed in the cortex and the lateral part of the basal ganglia. In a second group (n = 8), at 1 or 8 weeks after induction of the thrombosis in the MCA, the coronal sections were stained with hematoxylin and eosin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364231 TI - Gastric mucosal damage due to copper aspirinate. PMID- 8364232 TI - The differences between forensic psychiatry and forensic psychology. AB - Forensic psychiatry and forensic psychology face a common threat: the erosion of their credibility. It is proposed that they can combat this threat better by collaboration than by independent efforts. Similarities between the two professions are reviewed to examine their potential for collaboration. Their differences are reviewed to demonstrate the value of that which they can contribute collaboratively, beyond that which either can contribute independently, to increasing their credibility in the eyes of the public and the courts. Three specific areas for collaboration are proposed: individual practice, quality control of expert testimony, and training. PMID- 8364233 TI - Effects of professional affiliation on group therapists' confidentiality attitudes and behaviors. AB - This study examines the influence of group therapists' professional characteristics on their attitudes and practices regarding confidentiality. Eighty-three highly experienced and well-trained group therapy providers representing the fields of psychiatry, psychology, and social work completed a survey questionnaire inquiring into their confidentiality practices. Although there is considerable consensus between medical and nonmedical practitioners on the issues addressed, there are also interesting differences and trends. Implications of the findings for clinical practice, ethics training, and confidentiality legislation are addressed. PMID- 8364234 TI - Major mental disorder and antisocial personality disorder: a criminal combination. AB - Much evidence now suggests that patients with major mental disorders are at increased risk for crimes and violence. Leading experts in forensic psychiatry have proposed that the illegal behaviors are a consequence of these major disorders. Yet, longitudinal studies have consistently indicated that adult criminality is preceded by a childhood history of antisocial behavior. We hypothesized that among offenders with major mental disorders there are two groups: (1) the first group has a secondary diagnosis of antisocial personality disorder (APD), and a childhood history of antisocial and criminal behavior preceding the onset of the major disorder; (2) the second group do not meet the criteria for APD, and behave criminally only as adults. This hypothesis was tested on a representative sample of penitentiary inmates with major mental disorders. It was found that those with APD had a significant childhood history of criminal activity and antisocial behavior, endorsing, on average, eight of ten possible indices. In comparison, the mentally disordered inmates without APD endorsed on average two indices. The mentally disordered offenders with APD began their criminal careers earlier, and had significantly more convictions and more convictions for nonviolent offenses than those without APD. APD was not associated with violence among men with major mental disorders. PMID- 8364235 TI - The health care proxy for mental illness: can it work and should we want it to? PMID- 8364236 TI - How bad is civil commitment? A study of attitudes toward violence and involuntary hospitalization. AB - Civil commitment statutes throughout the nation authorize involuntary hospitalization for persons who are believed dangerous to others, even though clinicians' ability to predict violence is imperfect. Decision-makers faced with ambiguous evidence about future violence must make either-or decisions about involuntary hospitalization. Such decisions can be characterized as "true positives" (hospitalization of a person who would have acted violently if released), "true negatives" (nonviolent person is not hospitalized), "false positive" (nonviolent person is hospitalized), or "false negative" (person is released and subsequently acts violently). This paper presents two pilot studies of attitudes about false negative and false positive decisions, and explains how Decision Theory can use information gleaned from such studies to establish optimal decision thresholds for initiating involuntary hospitalization. Subjects expressed a broad range of implicit tolerances for false negative and false positive predictions. Though most subjects preferred being hospitalized for three days to being the victim of a knife-wielding attacker, a substantial minority preferred being attacked to being hospitalized. The article briefly explores the practical implications of these findings, which include an implicit endorsement of stringent commitment policies that would release a large fraction of potentially violent persons. PMID- 8364237 TI - Screening services in civil commitment of the mentally ill: an attempt to balance individual liberties with needs for treatment. AB - Screening services are a central feature of New Jersey's new civil commitment law. This law, more commonly referred to as the screening law, exemplifies a nationwide trend in civil commitment legislation, attempting to balance liberty interests and the need to treat the mentally ill. Screening services, designated as the preferred process of entry into involuntary hospitalization, were expected to prevent unnecessary commitment and to provide community mental health services. When deemed necessary, commitment in local general hospitals rather than in state mental hospitals was to occur. This paper reports results of a study of screening centers that were already in operation in New Jersey prior to the implementation of the new law. It assesses the function of screening services and their potential impact on the commitment process in light of the objectives of the law. Data were obtained from in-depth interviews with key informants from the screening centers as well as from their environment, and from statistical reports on hospitalizations in state hospitals, admissions to screening centers, and admissions to psychiatric inpatient units of general hospitals. Analysis suggests that without more resources for alternative community facilities, screening services cannot achieve their objectives and the new reform may not live up to expectations. Shortage of alternatives to hospitalization and lack of incentives to develop and use them appeared to be counterproductive to achieving the objectives of the law. The availability of screening service and psychiatric units in general hospitals for involuntary hospitalization, on one hand, and the lack of alternatives in the community, on the other, may actually lead to inappropriate commitments and an increase in the number of civil commitments. Furthermore, findings indicated that screeners encouraged hospitalization readily even if other, less restrictive environments could have been pursued. Screening centers may become "gate openers" instead of playing their expected role as "gate keepers." PMID- 8364238 TI - Memory processes in children: implications for investigations of alleged child sexual abuse. AB - Allegations of child sexual abuse naturally raise the ire of the populace at large, as well as the fears and apprehensions of those who may be falsely accused as perpetrators. Within this emotionally charged and litigious climate, the memory functions of children have become a matter of acute interest for those professionals involved in the ensuing investigations and legal proceedings. This is especially true, given that the child witness, approaching a court of law, is likely to encounter numerous circumstances that will invite memory distortion. These circumstances include interviews by concerned adults and protective service workers, as well as cross-examination by a defense attorney. Well-intentioned efforts may be replete with leading questions or subtle inferences that may distort episodic memory. The present paper will discuss developmental aspects of long-term memory functions in children, events, and cognitive processes that may contribute to memory distortion, and recommendations for improving procedures related to the investigations of alleged child sexual abuse. PMID- 8364239 TI - Toward the therapeutic use of obscene language: a legal and clinical review. AB - Obscenity has been the subject of a series of court cases centered around the First Amendment, and its interpersonal effects have been studied by psychotherapists and communications theorists. But little has been written about the impact of the use of obscenity by patients in group settings to discharge their feelings and to dominate and harass staff and other patients. The authors argue that if staff are to be able to work effectively with patient populations who utilize obscenity routinely for these purposes, they must become more comfortable with its use, and to treat it as another symptom of the patients' interpersonal difficulties. Guidelines for the therapeutic use/management of obscenity on the ward are offered. PMID- 8364240 TI - The relationship between insight and control in obsessive-compulsive disorder: implications for the insanity defense. AB - In this paper the authors examine the relationship between insight and control in patients with obsessive-compulsive disorder (OCD) in an effort to better understand the concept of volitional control of behavior especially as it relates to changes in the insanity defense that were recommended by the American Psychiatric Association (APA), specifically that the volitional prong be dropped. Yale-Brown Obsessive Compulsive Scale ratings in 56 subjects with OCD were reviewed with specific attention to items measuring the patients' subjective sense of decreased volitional control over their compulsions and their insight into their behavior. No statistically significant correlation was found between the control over compulsions item and the insight item. The authors conclude that the experience of volitional control in patients with OCD is not significantly related to the level of insight they have into the irrationality of their behavior. The authors then review cognitive therapy literature and show that though cognition and volition may appear to be dissociated in some disorders, even in the absence of insight, a relatively gross measure of legally relevant cognitive disturbance, subtle cognitive changes can be identified in patients with seemingly purely volitional disorders such as OCD. PMID- 8364241 TI - Infectious diarrhoea. Transmission and epidemiology. PMID- 8364242 TI - Mechanisms of diarrhoea. PMID- 8364243 TI - Escherichia coli diarrhoea. PMID- 8364244 TI - Other bacterial diarrhoeas. PMID- 8364245 TI - Infectious diarrhoea. Viruses. AB - Increased knowledge has been gained into the aetiology and pathogenesis of viral gastroenteritis during the past two decades. There are now thought to be four major subclassifications of gastroenteritis-causing viruses; these include rotavirus, enteric adenovirus, calicivirus, including Norwalk and Norwalk-like viruses, and astrovirus. The association of these agents with gastroenteritis has been made by their electron microscopic detection in stool and intestinal biopsy specimens from affected patients, the inability to detect the viruses after recovery from disease, and the subsequent development of immunoglobulin responses after infection; in some instances disease transmission was achieved in human volunteers. The association of these viral agents with gastroenteritis has facilitated the study of classification, epidemiology, immunity, diagnostic tests, methods of treatment and, most importantly, disease prevention strategies such as vaccine development for rotavirus. This chapter highlights the major features of these agents, with special attention being given to the pertinent molecular biology as well as current and future prospects for vaccination. Enteric viral infections of the gastrointestinal tract in patients with AIDS are also discussed. PMID- 8364246 TI - Intestinal parasites. PMID- 8364247 TI - Travellers' diarrhoea. AB - Although TD is usually a mild and self-limited illness, 30-50% of travellers from industrialized to less developed countries are affected. Enterotoxigenic E. coli (ETEC) remain the most frequent cause, being identified in 40-70% of cases. TD frequently occurs within the first 2 weeks of arrival in the foreign country. The clinical manifestation is variable, but watery diarrhoea is the most common clinical presentation. Chronic diarrhoea or remitting symptoms after empirical therapy in the returning traveller are indications for a stool culture and a careful search for stool parasites. Since the major precaution against TD is to avoid exposure to the infectious agents, careful selection of food and beverage is crucial. Bismuth subsalicylate has been proven to be safe and effective in the treatment and prophylaxis of TD. The tablet form has removed the inconvenience of previously required luggage space. Doxycycline, trimethoprim/sulphamethoxazole, trimethoprim and the quinolones have been shown to be effective for prevention of diarrhoea. However, side-effects, superinfection, development of antibiotic resistance and easy-to-treat illness may limit the use of these antimicrobial agents to those travellers with concomitant serious medical conditions that would be adversely affected by diarrhoea, or travellers with unaffordable temporary incapacity. A new oral-killed whole-cell and B-subunit cholera toxin vaccine was demonstrated to induce protection against severe ETEC-associated diarrhoea. This is a promising field under investigation. Finally, fluid replacement is the most important aspect of treatment. Patients with moderate to severe TD can be treated with one of the above-mentioned antimicrobial agents for 3-5 days. Selection of the antimicrobial agent is based on the pattern of resistance and the enteric organism prevalent in the geographical area. While TMP-SMX remains active against the strains prevalent in Mexico during summertime, the quinolones represent the choice for the therapy of diarrhoea acquired in the high-risk areas of South America, Africa and Asia. PMID- 8364248 TI - Diarrhoea in AIDS and other immunodeficiency states. PMID- 8364249 TI - Diagnostic procedures in the investigation of infectious diarrhoea. PMID- 8364250 TI - Rehydration and nutritional management. AB - Diarrhoea remains a leading worldwide cause of morbidity and mortality. In developing countries alone, 1.5 billion episodes of diarrhoea occur per year in children under 5 years of age and approximately 4,000,000 of these result in death. Early, appropriate therapy decreases the risk of complications and death due to diarrhoea. Regardless of the causative agent, oral rehydration and nutritional management are the mainstays of good management of infants, children and adults with diarrhoea. Diarrhoeal disease control programmes throughout the developing world have adopted the WHO case management plan as a standard. In this chapter, we review the history, successes and shortcomings of various oral rehydration therapies and recommend a case management approach that is similar to the WHO plan. Although ORT is safe, effective, convenient and economical, this therapy has not been universally implemented in health care settings. The challenge for clinical and public health practitioners in developing and developed countries is to identify and overcome the barriers that exist so that all patients with diarrhoea will have the opportunity to receive optimal care. PMID- 8364251 TI - Treatment of gastrointestinal infections. PMID- 8364252 TI - Vaccines to prevent enteric infections. AB - Considerable progress has been made in the last decade in developing vaccines against the enteric infections of greatest public health importance. A quadrivalent rotavirus vaccine consisting of rhesus rotavirus vaccine (which contains serotype 3 neutralization antigen) and three reassortant viruses (rhesus virus expressing neutralization antigens of serotypes 1, 2 or 4) is undergoing placebo-controlled field trials of efficacy in the USA and in two developing countries. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Even newer generations of typhoid vaccines are undergoing clinical testing, including new attenuated S. typhi strains and Vi polysaccharide-carrier protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated V. cholerae O1 bacteria alone or in combination with purified B subunit of cholera toxin, each conferred 50-53% protection over 3 years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. In extensive clinical trials in adults and children in less-developed countries, an engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown to be well tolerated and highly immunogenic following administration of just a single oral dose; a large scale field trial in 70,000 subjects is underway to investigate the efficacy of this vaccine. Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials. Accumulating knowledge on pathogenesis of enteric infections and advances in mucosal and cellular immunology, coupled with the application of modern biotechnology, have resulted in a plethora of vaccine candidates. It is expected that in future years efforts will be directed to construct vaccines against other enteric pathogens. PMID- 8364253 TI - Preventive strategies for the avoidance of infectious diarrhoea. PMID- 8364254 TI - Effects of 2',2'-difluorodeoxycytidine (Gemcitabine) on wild type and variant mouse leukemia L1210 cells. AB - 2',2'-Difluorodeoxycytidine (Gemcitabine, dFdCyd) is a cytotoxic agent which is active toward a variety of tumor cells. It has been shown that there are multiple intracellular sites of action which include ribonucleotide reductase and DNA polymerase. In these studies, the effects of dFdCyd on wild-type mouse leukemia L1210 cells and variant L1210 cell lines which had alterations at the ribonucleotide reductase site or at the deoxyribonucleoside kinase site were studied. For cell growth, the IC50 value for dFdCyd in wild-type L1210 cells was 3.1 nM. In the variant cell lines, the IC50 values were: hydroxyurea-resistant (HU), 3.3 nM; deoxyadenosine-resistant (Y8), 1.8 nM; pyrazoloimidazole/deoxyadenosine-resistant (ED2), 1.9 nM; and deoxyguanosine resistant (dGuo-R), 44.7 nM. The dGuo-R cell line had a relatively specific loss of the deoxyribonucleoside kinase responsible for phosphorylating deoxyguanosine and cytosine arabinoside with little loss of the deoxycytidine kinase activity. DFdCyd had no effect on the total uptake of [14C]cytidine into the cells or incorporation into RNA. DFdCyd inhibited the conversion of [14C]cytidine to deoxycytidine nucleotides and incorporation into DNA. However, the incorporation of cytidine into DNA was inhibited to a greater extent than was the inhibition of in situ ribonucleotide reductase activity. Ribonucleotide reductase activity in cell-free extracts prepared from L1210 cells treated with dFdCyd (20 nM) overnight was reduced by 50%. These results show that cell lines which have increased levels of ribonucleotide reductase activity (HU and ED2) or loss of feedback inhibition by dATP (ED2 and Y8) are still sensitive to dFdCyd. The findings indicate that ribonucleotide reductase is not the primary site of inhibition by dFdCyd.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364255 TI - Carboplatin-liposomes as activators of hematopoiesis. AB - Recombinant colony stimulating factors are studied in clinical trials with the purpose being the relief of the side effects of high dose chemotherapy and to make an optimized treatment regimen possible. The broad use of such factors is hindered by their relatively high costs, their short elimination half-lives, the occurrence of mild side effects, and the limitation of their action to the stimulation of mainly neutrophils. Therefore, exogenous preparations inducing an endogenous activation of hematopoiesis are being sought. In experiments in mice we have shown that carboplatin-liposomes injected intraperitoneally in a single dose of 100 mg/kg led to a strong two-peak increase in white blood cell counts. A maximum 10-fold elevation compared to controls of free carboplatin or empty liposomes was observed on day 2 and was probably due to the release and mobilization of cells from storage compartments. The second peak of about a 6 fold increase occurred on day 7-8 and can be seen as an indicator of bone marrow stimulation. Differentiation of blood cells revealed that neutrophils, lymphocytes and platelets multiplied. We presume that this effect of carboplatin liposomes is due to a relatively fast uptake of these vesicles by macrophages as their natural target. Within these cells carboplatin is metabolized, leading to an almost total loss of antineoplastic activity against the murine P388 leukemia. Concomitantly, cytokines are apparently induced in and released from macrophages producing secondarily hematopoietic growth factors either directly or in combination with other cytokines. An involvement of macrophages is indicated by the fact that an intraperitoneal pretreatment of mice with zymosan caused a partial but significant suppression of hematopoietic stimulation. In an in vitro colony forming assay of serum of mice treated 1, 3, or 7 days with carboplatin liposomes, the number of colonies increased 20-fold compared to serum from saline treated animals. Additionally, a combined intraperitoneal treatment of mice with 100 mg/kg of cyclophosphamide followed by carboplatin-liposomes one hour later demonstrated that prevention of cytostatic-induced leukopenia is possible by this method. Although the mechanism of stimulation of hematopoiesis by carboplatin liposomes is still partially unknown our results suggest that there should be further development of such a preparation for possible use in the treatment of cancer or other inherited or acquired hematopoietic disorders. PMID- 8364256 TI - Cytoplasmic membrane cholesterol and doxorubicin cytotoxicity in drug-sensitive and multidrug-resistant human ovarian cancer cells. AB - The possible involvement of cholesterol (CHOL) in the cellular transformations leading to the acquisition of the multidrug-resistance (MDR) phenotype has been evaluated in human ovarian cancer cells. To this end, the A2780 cell line and the 52-fold doxorubicin (DX)-resistant counterpart A2780-DX3 were analyzed under two different growth conditions: standard culture medium (FCS medium), or medium deprived of CHOL (LPDS medium). The following variables were investigated: free and esterified cytoplasmic membrane CHOL, cell growth, DX uptake and cytotoxicity, and low-density lipoprotein uptake and degradation (as indirect variables of CHOL homeostasis). The impact of the calcium antagonist verapamil (VER) on these variables was assessed. The results obtained indicate that under standard growth conditions, A2780 and A2780-DX3 cells are different not only with respect to DX uptake and sensitivity, but also with respect to membrane CHOL content and the ratio of free-to-esterified CHOL. The deprivation of lipoproteins in the culture medium, apart from slowing cell growth, induced a decrease in the cytoplasmic membrane CHOL content (mainly of the esterified form) that was particularly evident in A2780 sensitive cells. In LPDS medium, a reduced DX uptake occurred in both cell lines, but to a greater extent in A2780 cells, in which DX cytotoxicity decreased to values comparable to that of A2780-DX3 resistant cells. Restoration of DX sensitivity was achieved with the addition of 10 microM VER.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364257 TI - Identification of nitrosourea-resistant human rhabdomyosarcomas by in situ immunostaining of O6-methylguanine-DNA methyltransferase. AB - Cellular levels of O6-methylguanine-DNA methyltransferase (MGMT) correlate strongly with cellular resistance to carcinogenic and chemotherapeutic agents that produce adducts at the O6-position of guanine in DNA. Although biochemical and molecular assays can indicate the average MGMT content of tissues or tumors, they cannot distinguish mixed populations of cells, such as those that exist in tumor biopsy samples. We have determined MGMT at the cellular level in a panel of pediatric rhabdomyosarcoma xenografts by in situ immunostaining with a human MGMT specific antibody employing a very sensitive procedure that involves biotin avidin coupled horseradish peroxidase with silver-enhanced diaminobenzidine nickel staining. Two xenograft tumor lines known to be MGMT-deficient were not stained, whereas the nuclei in three MGMT-expressing lines were clearly stained. This is the first demonstration of an in situ procedure that discriminates drug sensitive MGMT-deficient tumors from drug-resistant MGMT expressing tumors. This procedure should prove useful, therefore, for predicting the susceptibility of tissues and tumors to O6-guanine alkylating agents. PMID- 8364258 TI - Reference listings in cancer research. PMID- 8364259 TI - Drug-related hospital admissions. AB - OBJECTIVE: To review and summarize studies reporting rates of drug-related hospital admissions. DATA SOURCES: Manual and computerized literature searches using MEDLINE, Index Medicus, and International Pharmaceutical Abstracts as databases (key words: drug, drug-related, or iatrogenic; admission, hospital admission, or hospitalization; and ADR or adverse drug reaction). References from retrieved articles were searched to locate further studies. STUDY SELECTION: Included were English-language studies of humans admitted to the hospital because of medications. Problems investigated were admissions prompted by adverse drug reactions (ADRs) when drugs were used by the patient and admissions resulting from a patient's noncompliant or unintentionally inappropriate drug use. Excluded were cases involving drug abuse, alcoholism, suicide attempts, intoxication, or inadequate prescribing. DATA SYNTHESIS: Between 1966 and 1989, ADR rates from 49 hospitals or groups of hospitals in a variety of international settings were published in 36 articles. Samples sizes ranged from 41 to 11,891 patients, with a median of 714 (interquartile range [IQR] 275-1245) and a mean of 1412 (SD 2233). The prevalence of reported admissions resulting from ADRs ranged from 0.2 to 21.7 percent; the median was 4.9 percent (IQR 2.9-6.7 percent) and the mean was 5.5 percent (SD 4.1 percent). The weighted meta-analytic estimate was 5.1 percent (95 percent confidence interval 4.4-5.8). Of those ADR admissions, 71.5 percent were side effects, 16.8 percent excessive effects, 11.3 percent hypersensitivity reactions, and 0.4 percent idiosyncratic; 3.7 percent of patients admitted for ADRs died. Eleven reports indicated that 22.7 percent of ADR hospitalizations were induced by noncompliance. CONCLUSIONS: Drug-induced hospitalizations account for approximately five percent of all admissions. Results apply only to people from highly developed industrialized countries. Economic analyses have not been performed. Future research should include the Third World and nonindustrialized nations as well as specific cultural groups. PMID- 8364260 TI - Comparative trial in volunteers to investigate possible ethanol-ranitidine interaction. AB - OBJECTIVE: To assess the effect of ranitidine on ethanol absorption after ethanol 0.5 g/kg is given in three single doses of 0.167 g/kg to simulate normal social drinking. DESIGN: A double-blind, placebo-controlled, crossover trial was performed in 16 healthy men. Ethanol serum concentrations were measured on day 6 of each of the three treatment periods (placebo, ranitidine 150 mg bid, or ranitidine 300 mg bid). METHODS: Ethanol 0.167 g/kg was administered followed by a standard meal at 1700. The last tablet of the test medication was given 15 minutes later. Thirty and 60 minutes after the first intake, the same amount of ethanol was given again. Serum ethanol concentrations were measured multiple times during the four-hour period following oral ingestion of the first dose. RESULTS: Comparison of median serum ethanol concentrations, the areas under the curve, peak and time to peak serum ethanol concentrations showed no significant differences during medication with placebo, ranitidine 150 mg bid, or ranitidine 300 mg bid. Peak ethanol concentrations (median values) were 153, 140, and 155 mg/L, respectively. CONCLUSIONS: This study shows that treatment with ranitidine, in a dose up to 300 mg bid, has no significant effect on serum ethanol concentrations, even when ethanol was given in divided doses to simulate normal patterns of social drinking. This implies that concomitant dosing with ranitidine will not increase the adverse effects of moderate doses of ethanol on concentration and psychomotor function. PMID- 8364261 TI - Theophylline disposition following parenteral feeding of malnourished patients. AB - OBJECTIVE: To investigate the effect of parenteral nutrition on theophylline disposition in malnourished patients. DESIGN: Before-after trial. SETTING: Tertiary care center. PATIENTS: Ten patients with historic, anthropometric, and laboratory evidence of malnutrition. INTERVENTIONS: Patients received two 5-mg/kg intravenous infusions of theophylline separated by at least 48 hours of glucose based parenteral nutrition providing the entire estimated nutritional requirements. MAIN OUTCOME MEASURES: Following each theophylline administration, serum theophylline samples were collected over a 24-hour period for delineation of maximum plasma concentrations, volume of distribution, elimination rate constant, clearance, and area under the curve. RESULTS: Peak plasma theophylline concentrations were significantly lower prior to feeding (5.3 mumol/L, 95 percent confidence interval [CI] 0.78-10.0 mumol/L, p = 0.028). Volume of distribution decreased after parenteral feeding (0.08 L/kg, 95 percent CI 0.006-0.15 L/kg, p = 0.037). The elimination rate of theophylline increased after parenteral feeding reflected by an increase in the elimination rate constant (0.06 h-1, 95 percent CI 0.01-0.10 h-1, p = 0.023). CONCLUSIONS: This study suggests that parenteral nutrition using a glucose-based solution acutely influences theophylline disposition in malnourished patients. PMID- 8364262 TI - Pharmacists' interventions using an electronic medication-event monitoring device's adherence data versus pill counts. AB - OBJECTIVE: To compare adherence data from an electronic medication-event monitoring device (MEMS, Aprex) with pill counts in assisting pharmacists in making recommendations regarding diabetes therapy. DESIGN: Two-month, double blind, randomized, controlled trial. SETTING: Veterans Affairs Medical Center ambulatory care clinics. PATIENTS: Forty-seven patients with poor to fair metabolic control of diabetes mellitus were enrolled. Patients were excluded if they were receiving insulin, had a concurrent infection, required child-resistant caps or medication remainder devices, or could not return for followup visits. Twenty patients were randomized to the MEMS and 27 to the control group (pill counts). Fasting plasma glucose concentrations were measured monthly and glycohemoglobin concentrations were measured at baseline and 60 days. Thirty-two patients were evaluable: 15 using MEMS and 17 using pill counts. INTERVENTION: Investigators made pharmacologic or educational recommendations to the patient's healthcare provider based on both laboratory data and MEMS readings in the treatment group or laboratory data and pill counts in the control group. MAIN OUTCOME MEASURE: Quantities and types of recommendations regarding diabetes therapy made by pharmacists using adherence data from the two methods were tabulated. RESULTS: In the MEMS group, 47 percent of the recommendations related to patient education compared with 12 percent in the control group (p = 0.028). MEMS data would have changed four recommendations in the control group to involve patient education. CONCLUSIONS: MEMS data resulted in different numbers and types of recommendations than pill counts. Pharmacists then could make specific recommendations regarding patient education before resorting to pharmacologic manipulations. PMID- 8364263 TI - Design, implementation, and use of a new antimicrobial order form: a descriptive report. AB - OBJECTIVE: To describe the development, implementation, and use of an antimicrobial order form. The article provides the design of the form and the rationale for including key aspects, and a report of the authors' experiences with the form over a three-year period. An analysis of compliance with the form and its impact on selected prescribing practices is also presented. DESIGN: Three thousand five hundred antimicrobial orders in four discrete sets over a three year period were analyzed to assess compliance and characterize prescribing patterns with respect to duration of therapy and dosing frequency. SETTING: The setting of the study was a 300-bed, university-affiliated, tertiary-care, teaching hospital. MAIN OUTCOME MEASURES: Analysis of the forms was organized into the following sections: (1) compliance with use of the form, (2) duration of therapy, and (3) impact on antimicrobial dosing intervals. RESULTS: Use of the form was essentially 100 percent. Seventy-eight percent of the forms had all required data elements completed in the period following implementation; this fell to 67 percent at the end of three years. Duration of surgical prophylaxis went beyond the recommended 24 hours in 10 percent of all cases in period 1, and in 18, 8, and 4 percent in periods 2, 3, and 4, respectively. Declines in inappropriate dosing frequency were seen with cefazolin (from 14 to 2.3 percent), ceftriaxone (from 23 to 4 percent), cefuroxime (from 21 to 0 percent), and clindamycin (from 43 to 7 percent). CONCLUSIONS: Our experience with implementation and use of the form was very positive. Significant difficulties with compliance were not encountered. Benefits of the form included reductions in the duration of surgical prophylaxis and in the frequency of inappropriate dosing intervals. PMID- 8364264 TI - Response to pancuronium after loss of atracurium-induced neuromuscular blockade. AB - OBJECTIVE: To describe a previously unreported event in which a patient became refractory to atracurium-induced neuromuscular blockade, but subsequently was adequately paralyzed with a standard dosage of pancuronium. CASE SUMMARY: A previously healthy 17-year-old woman who sustained multiple trauma developed tolerance to an atracurium infusion she was receiving while undergoing mechanical ventilation. On day 3 of neuromuscular blockade, she became unresponsive to atracurium as evidenced by excessive physical movement, increased peak airway pressures, and overbreathing assist control ventilation. Repeat boluses and increases in the atracurium infusion rate to a maximum of 1.27 mg/kg/h failed to provide a desired clinical response. A bolus dose of pancuronium 0.15 mg/kg was administered and the constant infusion was then changed to pancuronium 0.078 mg/kg/h. Within minutes, decreased respirations, peak airway pressures, and agitation were noted. The pancuronium infusion rate was then tapered to 0.045 mg/kg/h over 72 hours and continued to maintain adequate neuromuscular blockade. DISCUSSION: Potential pharmacokinetic and pharmacodynamic causes of loss of neuromuscular blockade in this patient are postulated. Possible explanations for loss of neuromuscular blockade include increased degradation of atracurium and/or a change in acetylcholine receptor physiology. CONCLUSIONS: The development of resistance to a specific neuromuscular blocking agent in the intensive care setting does not necessarily imply cross-tolerance or resistance to alternative agents. Also, loss of respiratory control by one neuromuscular blocking agent may be overcome by changing agents. PMID- 8364265 TI - Evaluation of plasmapheresis in the treatment of an acute overdose of carbamazepine. AB - OBJECTIVE: To report the use of plasmapheresis in the treatment of an acute overdose of carbamazepine. CASE SUMMARY: A 21-year-old black man was admitted unresponsive and combative following a carbamazepine overdose. The total body load of carbamazepine was approximated at 5.91 g using an assumed volume of distribution of 1.4 L/kg. The patient underwent three plasmapheresis treatments. A total of only 335.82 mg of carbamazepine was removed by this process. DISCUSSION: Case reports in the literature were reviewed and compared. Carbamazepine concentrations lack correlation with the clinical outcome. Our patient's symptoms were consistent with the Weaver classification system. Carbamazepine clearance increased by almost 70 percent above its natural clearance during plasmapheresis. However, a significant rebound effect was observed after plasmapheresis: 40.1 percent after the first and 18.3 percent after the second treatment. CONCLUSIONS: Plasmapheresis did not seem to have a great impact on the patient's clinical status. Under the circumstances we find it extremely difficult to recommend plasmapheresis in the treatment of an acute overdose of carbamazepine. PMID- 8364266 TI - Intrathecal administration of amikacin for treatment of meningitis secondary to cephalosporin-resistant Escherichia coli. AB - OBJECTIVE: To report a case of gram-negative bacillary meningitis (GNBM) secondary to cephalosporin-resistant Escherichia coli that was treated with intrathecal and intravenous amikacin and intravenous imipenem/cilastatin (I/C). CASE SUMMARY: A patient who had undergone two recent neurosurgical procedures developed GNBM and bacteremia. He was treated empirically with ceftazidime. Both bloodstream and cerebrospinal fluid isolates were identified as E. coli, resistant to third-generation cephalosporins, penicillins, tobramycin, and gentamicin. The patient was subsequently treated with intravenous and intrathecal amikacin plus intravenous I/C. He experienced subjective and objective improvement on days 2-4 of antimicrobial therapy; two generalized tonic-clonic seizures occurred on days 7 and 12. Intrathecal amikacin was discontinued after 6 days, and intravenous amikacin and I/C were discontinued after 23 and 27 days, respectively. The patient's mental status did not completely return to premeningitis baseline. DISCUSSION: Third-generation cephalosporins are the treatment of choice for GNBM. In the case reported herein, bacterial resistance to these agents prompted the use of a therapy that has not been well studied and is also considered to be less safe and perhaps less efficacious. Treatment of GNBM with an intrathecally administered aminoglycoside or with intravenous I/C plus an aminoglycoside is reviewed. CONCLUSIONS: Patients with GNBM secondary to third-generation cephalosporin-resistant organisms may require therapies that may be less effective and more toxic. Further study of alternative agents is warranted. PMID- 8364267 TI - Acute verapamil toxicity in a patient with chronic toxicity: possible interaction with ceftriaxone and clindamycin. AB - OBJECTIVE: To report a case of acute toxicity in a patient with chronic verapamil toxicity, possibly precipitated by intravenous administration of the highly protein-bound drugs ceftriaxone and clindamycin. DATA SOURCES: Case reports, review articles, and relevant laboratory and clinical studies identified by MEDLINE (1984-forward), and relevant cross references from those articles. DATA EXTRACTION: Data were abstracted from pertinent sources by one author and reviewed by the remaining authors. CASE SUMMARY: A 59-year-old man who had been receiving sustained-release verapamil 240 mg q12h for more than two years for hypertension, and phenytoin 300 mg/d for many years for prophylaxis against seizures, was noted to be in junctional rhythm when he presented to the emergency room with bilateral pneumonia. Administration of intravenous ceftriaxone 1 g and clindamycin 900 mg precipitated symptoms of acute verapamil toxicity in this patient. The toxicity led to complete heart block requiring cardiopulmonary resuscitation and insertion of a temporary pacemaker. He spontaneously reverted to normal sinus rhythm after 16 hours. Subsequent cardiac evaluation, including echocardiogram, 48-hour dynamic electrocardiographic recording (Holter), and exercise stress test were normal. The patient has remained in sinus rhythm for more than one year after this episode. CONCLUSIONS: We believe that junctional rhythm on admission was a result of chronic verapamil toxicity. This may have been because of increased bioavailability of the drug or increased sensitivity of the receptors. Administration of ceftriaxone, clindamycin, or both agents might have precipitated acute verapamil toxicity by displacing verapamil from its protein-binding sites. Extreme caution is necessary when a highly protein-bound drug is given to a patient already receiving verapamil. PMID- 8364268 TI - Cefuroxime-induced fever. AB - OBJECTIVE: To report on three patients with cefuroxime-induced fever. CASE SUMMARIES: Recurrence of fever was noted in three patients after five to seven days of cefuroxime sodium therapy for acute exacerbation of chronic obstructive pulmonary disease. No source of infection was found and the fevers resolved within 30 hours of drug discontinuation. One patient was rechallenged; the same pattern of fever resulted. DISCUSSION: Fever secondary to cephalosporin administration is reviewed and the place of cephalosporins in the differential diagnosis of fever is postulated. CONCLUSIONS: Cefuroxime should be added to the list of cephalosporins that induce fever. PMID- 8364269 TI - Baclofen-induced bronchoconstriction. AB - OBJECTIVE: To report the occurrence of acute bronchospasm in one asthmatic patient and increased bronchial reactivity in another following the administration of a single dose of oral baclofen. CASE SUMMARY: On two separate occasions, a 46-year-old asymptomatic asthmatic man developed dyspnea and chest tightness one hour after the ingestion of baclofen 40 mg. Pulmonary function studies revealed a significant decrease in airflow relative to baseline. A 33 year-old asymptomatic woman with a history of exercise-induced dyspnea and wheezing displayed bronchial hyperresponsiveness to inhaled metacholine 2 hours after ingesting 40 mg of baclofen. The patient had had a negative methacholine challenge test 72 hours earlier. DISCUSSION: The gamma-aminobutyric acid-agonist baclofen has been shown to reduce airway responsiveness to various bronchoconstricting agents in animal studies. The etiology of this seemingly paradoxical response in two patients is unclear, but may offer insight into the neurally mediated airway constriction that occurs in asthma. CONCLUSIONS: Clinicians should be aware of the possibility of baclofen-induced bronchospasm, especially in asthmatic patients. PMID- 8364270 TI - Clindamycin-induced lip and nasal passage swelling. AB - OBJECTIVE: To report a severe case of clindamycin-induced lip and nasal passage swelling. DESIGN: Single case report. SETTING: Six hundred eighty-four-bed community hospital. CASE SUMMARY: A 34-year-old, insulin-dependent diabetic white man with worsening cellulitis and osteomyelitis of the left great toe was admitted for treatment with intravenous antibiotics. Intravenous clindamycin was the first agent administered. Within 5 minutes after initiating the drug (600-mg dose) the patient began to sneeze and his eyes began to tear and itch. Within 10 minutes, his lips and nasal passages began to swell. By the end of the infusion (approximately 20 min), the patient's lips were severely swollen and his nasal passages were completely closed off secondary to the swelling. The patient did not have difficulty breathing through his mouth and denied any shortness of breath. He did not develop a rash. His vital signs remained stable and no pharmacologic agents were administered for this reaction. No subsequent doses of clindamycin were given and complete resolution of all symptoms occurred within 24 hours. CONCLUSIONS: Severe lip and nasal passage swelling is an uncommon adverse reaction associated with the use of intravenous clindamycin. We believe this to be the first published case of nasal passage swelling and only the second case reporting lip edema associated with the intravenous form of this agent. Clinicians should be aware of this uncommon but potentially severe reaction. PMID- 8364271 TI - Effect of heat treatment of potentially infected blood samples on therapeutic drug monitoring of selected drugs. AB - OBJECTIVE: To investigate the effect of heart treatment on the outcome of drug analysis in whole blood and serum for eight drugs routinely assayed for therapeutic monitoring. DESIGN: All blood and serum samples (n = 373) received at the pharmacy laboratory for therapeutic monitoring of carbamazepine, digoxin, gentamicin, kanamycin, phenobarbital, phenytoin, theophylline, and valproic acid were heated at 60 degrees C for 30 minutes. Serum was subsequently assayed by fluorescence polarization immunoassay (TDx). SETTING: The study was conducted at the analytical laboratory of the pharmacy, using standard laboratory procedures. MAIN OUTCOME MEASURES: Analyses of heated samples were compared with analyses of untreated samples using a paired Wilcoxon signed-rank test. RESULTS: Serum concentrations of phenytoin from treated whole blood, and gentamicin in treated serum, were significantly lower than in untreated samples. These differences, however, were small, clinically irrelevant, and lie within assay variation intervals. Heat treatment did not influence the outcome of analyses for carbamazepine, digoxin, kanamycin, phenobarbital, theophylline, and valproic acid. CONCLUSIONS: Heat treatment of whole blood and serum samples of the investigated drugs does not influence the outcome of drug analysis, although drug instability cannot be fully excluded. Heat treatment can protect laboratory technicians from HIV infection without influencing therapeutic monitoring of these drugs. PMID- 8364272 TI - Hematologic effects of ethanol consumption in trauma patients. AB - OBJECTIVE: To determine the effects of ethanol (EtOH) ingestion by trauma patients on the hematologic system as evidenced by coagulation abnormalities and transfusion requirements. DESIGN: Retrospective chart review. The injury severity score (ISS) was determined for each patient. Patients were grouped according to presence of EtOH (+EtOH) and absence of EtOH (-EtOH) with further subdivision based on an ISS < or = 8 or > or = 9. SETTING: University medical center. PATIENTS: All adult trauma patients admitted during a one-month period. MAIN OUTCOME MEASURES: The volume of resuscitation fluids (including blood products) administered, laboratory parameters indicative of bleeding, and length of stay. RESULTS: Of 104 evaluable patients, 38 had measurable EtOH concentrations, 46 had undetectable EtOH concentrations, and the remaining 20 patients had not been tested. Although isolated, statistically significant differences were found among groups for some of the outcome measures, there were no clinically important differences. CONCLUSIONS: EtOH ingestion prior to injury did not appear to cause significant alterations in the hematologic system of trauma patients, but a larger study is needed to confirm these findings. PMID- 8364274 TI - Amantadine and fatigue of multiple sclerosis. PMID- 8364273 TI - Accuracy of vancomycin serum concentrations in patients with renal failure. PMID- 8364275 TI - Use of tricyclic antidepressant concentrations to determine individual response. PMID- 8364277 TI - Current issues surrounding women and minorities in drug trials. AB - OBJECTIVE: Our principal objective is to make readers aware of conflicting demands placed on investigators and the pharmaceutical industry regarding inclusion of women and minorities in clinical research. Tremendous pressures have been placed to expedite the drug approval process. Moreover, during the last decade certain segments of society, particularly women and minorities, have demanded greater participation in clinical drug trials and earlier access to investigational drug therapies. Regulations that have served the clinical research community (pharmaceutical industry, investigators, institutional review boards) as guidelines for safe conduct of human clinical trials are being challenged by social and political change. This article provides an overview of some of the controversy relative to federal regulations governing clinical trials; scientific concerns; social, political and legal trends; and ethical principles applied to human clinical research. DATA SOURCES: Literature for this paper was retrieved from a variety of sources including the nonmedical press, editorials, peer-reviewed journals, Department of Health and Human Services regulations, National Institutes of Health policy, the Belmont Report, and regulations of the Food and Drug Administration. DATA SYNTHESIS: Scientists evaluating new therapeutic agents ask specific research questions to assess safety, efficacy, and the mechanism(s) of action. Because of concerns for scientific validity, safety, liability, and convenience, many early evaluations of new drugs involve patient populations that may not represent the ultimate users of a new drug. Federal regulations and ethical principles allow certain groups of people to be excluded from early research proposals because they are thought to be putting themselves at greater risk by participating than are other groups. However, women, minorities, and other populations are demanding greater access to investigational drugs. The focus has changed from protection from research risks and burdens to the potential benefits a person or class of people may obtain by participating in a study. CONCLUSIONS: Scientists, the pharmaceutical industry, regulators, and society must agree on a safe and efficient mechanism for new drug development that permits more equitable participation of subjects in the various phases of research. PMID- 8364276 TI - Leukotriene-receptor antagonists and 5-lipoxygenase inhibitors in asthma. AB - OBJECTIVE: To familiarize readers with a potentially new class of compounds for treating asthma. Background information on leukotrienes is provided in addition to an in-depth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trials, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more promising results. DATA EXTRACTION: Information regarding leukotriene biochemistry was extracted from basic science research and data from human studies were evaluated by the authors according to patient selection, study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are currently being clinically evaluated. These are leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug potency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators in asthma and, consequently, have shown promising clinical outcomes with respect to pulmonary function testing and patient tolerance. CONCLUSIONS: Advancements in the pathogenesis of asthma are beginning to define a role for the leukotrienes. Although more studies are needed to assess the efficacy of leukotriene inhibitors, recent clinical trials using leukotriene-receptor antagonists and 5 lipoxygenase inhibitors indicate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma. PMID- 8364278 TI - Vancomycin administration into the cerebrospinal fluid: a review. AB - OBJECTIVE: To discuss administering vancomycin directly into the cerebrospinal fluid (CSF) to treat serious central nervous system (CNS) infections. DATA SOURCES: References were obtained through an online search of MEDLINE, limited to material published in English. In addition, information was extracted from clinical trials, review articles, abstracts, and textbooks. STUDY SELECTION: Systematic evaluation of this topic in humans has not been done in a prospective manner. Related research articles describing the pathophysiology of CNS infections, intrathecal drug administration, and case reports of CSF vancomycin administration were reviewed. DATA EXTRACTION: Case reports regarding CSF vancomycin dosing were evaluated and included: drug dosing, infecting organism, infectious disease state, infectious outcome, CSF dynamics/flow abnormalities, methods of drug administration, drug monitoring, and toxicities. DATA SYNTHESIS: The results of this review are based on qualitative evaluations of anecdotal case reports and a basic understanding of intrathecal and intraventricular drug dosing principles. CSF administration of vancomycin is an effective means of bypassing the blood-brain barrier to achieve greater drug concentrations within the CSF. Current limitations to the CSF administration of vancomycin include a lack of data describing its safety, efficacy, and pharmacokinetics. CONCLUSIONS: CNS infections may require the CSF administration of vancomycin for successful eradication. Recommendations for dosing in the literature vary. Because of the potential toxicities associated with elevated CSF concentrations of vancomycin, dosing should be conservative. PMID- 8364279 TI - Assessment of patient acceptance and inhalation technique of a pressurized aerosol inhaler and two breath-actuated devices. AB - OBJECTIVE: To assess inhalation technique in patients after written instruction alone, written and verbal instruction, and clinical use of two new inhalation devices. DESIGN: Randomized, crossover evaluation of the albuterol Diskhaler and the terbutaline Turbuhaler. SETTING: Canadian tertiary-care hospital. PATIENTS: Twenty hospitalized adults with asthma or chronic obstructive pulmonary disease currently using an albuterol metered-dose inhaler (MDI). Nineteen patients received Diskhaler, 16 received Turbuhaler, 15 received both inhalers, and 10 patients used both inhalers for three days each. INTERVENTIONS: Patients were randomized to receive either Diskhaler or Turbuhaler for three days. Inhaler technique was assessed after written instruction, written plus verbal instruction, at the first scheduled dose after instruction, and after three days of clinical use. Patients remaining in the hospital after three days crossed over to the other study inhaler and the same protocol was followed. MAIN OUTCOME MEASURES: Patient inhalation technique was assessed and compared for the MDI, Diskhaler, and Turbuhaler. RESULTS: Assessment of MDI technique revealed that 35 percent of patients used their MDI correctly on the first puff, and 42 percent used it correctly on the second puff. Following written instruction alone, correct technique was demonstrated by 32 percent of patients with Diskhaler and 6 percent with Turbuhaler. Technique significantly improved following verbal instruction, although 40 percent of the patients required up to three attempts to demonstrate correct technique on at least one of the study inhalers. After three days of clinical use, correct technique was demonstrated in only 54 percent of the Diskhaler and 64 percent of the Turbuhaler assessments. Performance at this assessment was, however, significantly better on the Turbuhaler than on the MDI (p = 0.01). Performance on the Diskhaler was not significantly different from the performance on the other inhalers. CONCLUSIONS: Written instruction alone is inadequate in teaching correct inhalation technique. Verbal instruction and technique assessment are essential for patients to achieve proper technique. Patients may perform better on the Turbuhaler than on other inhalation devices. PMID- 8364280 TI - Controversies in the management of Mycobacterium avium complex infection in AIDS patients. AB - OBJECTIVE: To update readers on the clinical management of infections secondary to Mycobacterium avium complex (MAC) in patients with AIDS. A general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease is provided. Several aspects of the treatment of the disease, including an historical perspective, current approaches, and future research opportunities, are described. DATA SOURCES: Current medical literature, including abstracts presented at international meetings, is reviewed. References were identified through MEDLINE, Current Contents, and published meeting abstracts. STUDY SELECTION: Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of MAC are cited. Specific attention is given to the management of patients with MAC infection. DATA EXTRACTION: Information contributing to the discussion of the topics selected by the author is reviewed. Data supporting and disputing specific conclusions are presented. DATA SYNTHESIS: Disseminated MAC infection is diagnosed antemortem in approximately 30 percent of patients with AIDS; postmortem rates of isolation exceed 50 percent. The incidence of MAC may increase as attempts at isolating the organism become more aggressive. The traditional approach to the isolation, susceptibility testing, and treatment of MAC has been derived from the management of Mycobacterium tuberculosis, with disappointing results. Newer radiometric in vitro methods of susceptibility testing appear to show more promise. Current mouse models of MAC are not true AIDS models; new CD4-deficient mouse models are being developed. Clinical mycobacteriologic and pharmacokinetic laboratory support have been underused, with treatment generally proceeding empirically. New agents that may contribute to the management of disseminated MAC infection include the macrolide derivatives clarithromycin and azithromycin. Research also continues with new rifamycins (including rifabutin) and fluoroquinolones (ciprofloxacin, sparfloxacin). Preliminary results suggest a central role for macrolides in the treatment of disseminated MAC; effective companion drugs are needed to prevent the rapid emergence of macrolide-resistant MAC. CONCLUSIONS: Treatment results for disseminated MAC infection remain poor. Therapy may be improved by selecting drugs on the basis of susceptibility data for each isolate, rather than by using empiric regimens based on susceptibility trends. Significant antimycobacterial drug malabsorption has been documented, and may contribute to poor outcomes. More-potent agents are needed to improve the clinical outcome in AIDS patients with MAC. PMID- 8364281 TI - Erythromycin-induced hypoacusis: 11 new cases and literature review. AB - OBJECTIVE: To report 11 cases of possible erythromycin-induced hearing loss and to review all cases reported in the literature. CASE SUMMARY: In the 11 cases reported, the following are reviewed: age, gender, time to onset of and recovery from hypoacusis in relation to erythromycin administration, presence or absence of renal or hepatic disease, underlying disorders, and concurrent administration of other drugs. Hypoacusis appeared with dosages equal to or higher than 4 g/d in patients with a mean age of 52.5 +/- 19 years, a high percentage of whom (45 percent) presented with renal impairment. The hearing loss was reversible in all cases, and subsided a few days (median = 3) after dosage reduction or drug discontinuation. DISCUSSION: Our patients' characteristics are similar to those of patients reported in the literature. Most data indicate that erythromycin induced hypoacusis is a dose-dependent effect; however, its occurrence in patients otherwise free from disposing factors suggests that it is idiosyncratic. CONCLUSIONS: Erythromycin administered for appropriate indications and dosage adjustments in patients with impaired renal and/or liver function may prevent or reduce the incidence of erythromycin-induced hypoacusis. PMID- 8364282 TI - Pharmacoepidemiology of bleeding events after use of r-alteplase or streptokinase in acute myocardial infarction. AB - OBJECTIVE: To determine in nonresearch, general medical practice conditions the comparative incidence and types of bleeding complications after the use of streptokinase (SK) and r-alteplase (recombinant tissue plasminogen activator, rt PA) to treat acute myocardial infarction (AMI). DESIGN: Retrospective medical record review of concurrently treated patients (96-hour observation posttreatment) in 32 participating hospitals in the US. MAIN OUTCOME MEASURES: The medical record description of all bleeding events regarding the body site affected, changes in hemoglobin concentrations, blood products administered, and clinical outcome (permanent sequelae or death). Bleeding severity was determined by defined criteria. CONTROL DATA: Comorbidity and concomitant medications (e.g., aspirin, heparin, warfarin) likely to predispose or contribute to bleeding events were analyzed. DATA ANALYSIS: Logistic regression analysis. RESULTS: Data from 419 patients who received rt-PA and 207 who received SK were evaluated. In the 96 hour period after initiation of thrombolytic therapy, 30.5 and 31.9 percent of rt PA and SK patients, respectively, experienced one or more bleeding events (crude risk ratio [CRR] = 1.04; 95 percent confidence interval [CI] 0.91-1.14; p = 0.73). In the first 24-hour period, 21.5 percent of rt-PA and 15.9 percent of SK patients experienced bleeding events (CRR = 0.74; 95 percent CI 0.42-1.15; p = 0.08). The leading types of bleeding and percents of all patients affected were: perivascular access site (18.4 percent), gastrointestinal (6.4 percent), skin/soft tissue/muscle (5.0 percent), urinary (3.4 percent), pulmonary (2.2 percent), systemic (1.9 percent), and oral (1.4 percent). Intracranial bleeding occurred in 4 rt-PA and 2 SK patients; 4 of these patients died. Events deemed clinically significant occurred in 15 rt-PA and 9 SK patients (3.8 percent of all patients). Ten patients likely died from these events, 6 within the first 24 hours. Three rt-PA patients and 1 who received SK (0.6 percent) died of cerebrovascular events within the first 24 hours. After controlling for demographic factors and therapeutic variables, using logistic regression analyses, no thrombolytic-related differences were found in the incidence or severity of bleeding following use of the two thrombolytics. CONCLUSIONS: These clinical data do not support a theoretical advantage of rt-PA to cause less bleeding propensity than SK. PMID- 8364283 TI - Computerized monitoring protocols as a pharmaceutical care practice enhancement: a conceptual illustration using diabetes mellitus. AB - OBJECTIVE: To illustrate how a computer system used in an ambulatory care pharmacy setting might enhance care of patients with diabetes by prospectively monitoring and prompting them to seek routine medical care. DATA SOURCES: A MEDLINE search to identify existing works on informatics was conducted. An epidemiology and general medical literature review of diabetes mellitus was also performed via MEDLINE. Additionally, known textbooks on the disease were consulted. CONCLUSIONS: Programming a computer system to prompt pharmacists to remind their patients of necessary medical interventions could save medical resources by warning chronically ill patients not to ignore routine medical care. Also, this would allow the pharmacist to prospectively monitor patient outcomes. By knowing when medical interventions are due and obtaining feedback from patients on the results of the medical contact, pharmacists increase their knowledge about patient outcomes and the rationale behind changes in pharmacotherapy. It is expected that such a system would prevent the inconspicuous development of chronic complications. PMID- 8364284 TI - Ceftazidime dosing in the elderly: economic implications. AB - OBJECTIVE: This study evaluated the prevalence and resulting costs of ceftazidime dosing in excess of product labeling recommendations in elderly hospitalized patients. Ceftazidime is a beta-lactam antibiotic excreted via glomerular filtration. According to product labeling, ceftazidime dosing can frequently be decreased in the elderly because glomerular filtration declines with age. METHODOLOGY: A multicenter, retrospective utilization audit involving 11 US academic medical centers examined 221 medical records of patients 65 years of age or older receiving ceftazidime (any brand, any indication). The creatinine clearance of each patient was estimated using the Cockcroft-Gault formula. RESULTS: Renal insufficiency, defined as an estimated creatinine clearance of less than 50 mL/min, was present in 111 of the patients (50 percent). Ceftazidime dosing in excess of product labeling recommendations was noted in 75 of those 111 (68 percent). The cost of excess ceftazidime dosing for those 75 patients (i.e., extra drug acquisition, preparation, administration) was $13,822.50. CONCLUSIONS: Although the dosage of ceftazidime required in a specific patient is based on many factors, ceftazidime is frequently overdosed in the elderly because renal function is not considered. Ceftazidime dose-adjustment in the elderly, based on the estimated creatinine clearance, can lead to cost savings. In the US, where hospital reimbursement by Medicare is based on diagnosis, institutions can realize direct cost savings. PMID- 8364285 TI - Gender and racial bias in clinical pharmacology trials. PMID- 8364286 TI - Prescription of antimicrobial drugs to hospitalized children. AB - OBJECTIVE: To analyze with regard to age, gender, and diagnosis, the profile, frequency of prescribing, and cost of antimicrobial drugs (AMDs) in hospitalized children. DESIGN: Retrospective study of medical records of children hospitalized during 1987 and 1988. SETTING: First Pediatric Clinic, Children's Teaching Hospital, Bratislava, Czechoslovakia (now Slovakia). PATIENTS: One thousand randomly selected hospitalized children. MAIN OUTCOME MEASURES: Patterns of AMD prescribing. Consumption is expressed by the number of drugs and cost per child. RESULTS: AMDs were prescribed to 69.9 percent of the patients (average 1.91 per patient). Ampicillin was the drug most frequently prescribed (20.0 percent), followed by oxacillin (12.8 percent). The mean length of stay was 15.9 days. An average of 3.61 drugs from other pharmacotherapeutic categories were prescribed per patient. Most children who received AMD treatment were in the 1-year group (patients between six months and 1.5 years of age [88.6 percent]). CONCLUSIONS: This study provides an overview of the prescribing of AMDs and other drugs in hospitalized children in Bratislava. PMID- 8364287 TI - Use of theophylline to control hematocrit in respiratory polycythemia. PMID- 8364289 TI - Perforation of colon diverticula during corticosteroid therapy for pemphigus vulgaris. PMID- 8364288 TI - Ketorolac and gastrointestinal ulceration. PMID- 8364290 TI - Clonidine-induced hyperglycemia in a young diabetic girl. PMID- 8364291 TI - Hydrocortisone-colestipol interaction. PMID- 8364292 TI - Treatment of cavernous hemangioma with vincristine. PMID- 8364294 TI - Gemfibrozil-induced impotence. PMID- 8364293 TI - Drug utilization evaluation of imipenem/cilastatin in patients with renal dysfunction. PMID- 8364296 TI - AHNA certificate program in holistic nursing courses. AHNA certificate program in healing touch courses. PMID- 8364295 TI - Comment: aminoglycoside dosing considerations. PMID- 8364297 TI - The right to die: who should choose? PMID- 8364299 TI - Talking to patients about sexual matters. AB - Specific counselling skills that will assist nurses in discussing sexual matters with patients can be learned. The possession of such skills by nurses will enhance the nurse/patient relationship and encourage patients in the era of HIV/AIDS, to discuss their concerns about sexual issues more openly. This article describes the place of conversation about sexual matters with patients. PMID- 8364300 TI - Treatment and prevention of hypothermia. AB - The onset of winter is the time when many voluntary agencies begin their campaigns regarding the dangers of the cold upon the elderly population. It is also the time when accident and emergency nurses treat the highest proportion of such people presenting in various degrees of accidental hypothermia. This article outlines the care required and highlights the health education advice needed to minimize the problem. PMID- 8364298 TI - Is quality assurance just a theoretical pedestal? PMID- 8364301 TI - Therapist self-disclosure in behavioural psychotherapy. AB - Therapist self-disclosure has been poorly defined until recently. This article presents a model of verbal self-disclosure and relates it to both client-centred therapy and counselling as social influence. The implications for behavioural psychotherapy are then reviewed. PMID- 8364302 TI - Prevention and management of pressure sores. AB - Continuity of care is needed when transferring patients at risk of developing pressure sores. The tools used to assess such patients must be consistent. A turning clock system has been developed for use with the patient. PMID- 8364303 TI - Management of lymphoedema: a community-based approach. AB - The community-based Enfield Lymphoedema Service received over 100 referrals in its first year, which suggests that it is suitably sited in the community. Patients have been offered previously unavailable information and treatment, while health care professionals have gained an improved awareness of and insight into lymphoedema and its treatment. PMID- 8364305 TI - Nurses should welcome a wider scope of practice. PMID- 8364304 TI - Quality management in a college of nursing and midwifery. AB - Colleges of nursing and midwifery are experiencing great change in their working environment and are now expected to offer cost-effective, high quality training and education. Mid Trent College of Nursing and Midwifery has met the challenge by introducing quality management strategies. This article explores their development. PMID- 8364306 TI - The living will: implications for nurses. AB - In certain states in the USA there has been, for some time, the right in law for patients who are terminally ill to declare their 'living will'. This article examines the concept of the living will and the situation surrounding euthanasia in Britain and Europe. Its aim is to give nurses further insight into and greater understanding of the possible future use of a living will. PMID- 8364308 TI - Nurses must adapt to changes in hospital psychiatric care. PMID- 8364307 TI - Legal aspects of first aid and emergency care: 2. AB - The first article in this series examined the nurse's duty to act at the scene of an accident. This article explores this theme further by looking at the legal implications and the four arenas of accountability. PMID- 8364309 TI - Nurses are wrong to outlaw all ritualistic practices. PMID- 8364310 TI - The role of nurses in counselling the terminally ill patient. AB - Facing one's own death is emotional, traumatic and frightening. Nurses can help patients and their families to cope with this crisis through the sensitive use of counselling skills. In so doing they will also become more aware of their own beliefs and feelings surrounding the subject. PMID- 8364311 TI - Attitudes of professionals to drug abusers. AB - Drug abusers are generally regarded as a demanding client group by health care professionals. The occupational background of health care professionals and their familiarity with drug users is likely to affect their emotional responses and attitudes. Professional carers who are more familiar with drug users, e.g. addiction counsellors and psychiatric nurses, tend to have a more positive attitude. Awareness of HIV infection may increase the fears and anxieties of professionals, resulting in a more negative attitude to drug users. Little research has been carried out into the attitudes of professional carers, particularly nurses, towards drug users. Attitudes of professional carers are very important in determining standards of care delivery and more research is needed into the effects of attitudes on the delivery of health care. PMID- 8364312 TI - Dimensions of nursing knowledge in wound care. AB - There is continuing debate as to whether nursing is an art or a science. This seems to be further fuelled by discussion about whether nursing is a profession. If nursing could be called a research-based science, would it become a recognized profession and be taken more seriously? This article relates the art/science debate to the teaching of wound care in clinical practice. PMID- 8364313 TI - Management of chronic obstructive airways disease. PMID- 8364314 TI - Can nurses take an accurate blood pressure? AB - It is over 20 years since the Briggs (1971) report extolled the virtues of nursing becoming a research-based profession. However, despite progress having been made towards achieving a research base, studies all too rarely inform nursing practice. This article offers a number of explanations for this failure and demonstrates the benefits of research by examining nurses' knowledge of the factors that are important in taking an accurate blood pressure reading. PMID- 8364315 TI - Accountability in nurse education. AB - Accountability has assumed a higher profile in these changing times and clearly this multifaceted concept is inextricably linked to professionalization. In addition, major changes have taken place in nurse education, resulting in role changes for the nurse teacher. Consequently, nurse teachers will have to examine more closely the many facets of accountability. PMID- 8364316 TI - Nurse practitioner title: ambiguous and misleading. PMID- 8364317 TI - Legal aspects of first aid and emergency care: 3. AB - The first and second articles in this series considered whether there was a duty in law to volunteer help when there was no pre-existing duty to do so and discussed the standard of care that should be followed. This article examines the volunteer's rights if he/she is injured while assisting at an accident. PMID- 8364318 TI - Who deserves care? PMID- 8364319 TI - When is holism not complementary? PMID- 8364320 TI - Introducing high quality infection control in a hospital setting. AB - Hospital infection is a quality issue and as such has become an important topic in the current health care debate. Quality assurance and resource management are becoming integral to the measurement of nursing standards in clinical practice. Quality assurance is, in many ways, inseparable from effective infection control. This article outlines the development of such a high profile demonstration unit named Quality Infection Control (QIC) and discusses its strengths and weaknesses. PMID- 8364321 TI - Preoperative ophthalmic procedures: ritualistic or necessary? AB - Routine ophthalmic nursing tasks are often seen as unnecessary, degrading the skill of the ophthalmic nurse in assessing, planning and implementing the care of the patient. Many ophthalmic departments have discontinued such tasks, but the reasoning and the consequences do not appear to have been documented. PMID- 8364322 TI - Discovering theory from psychiatric nursing practice. PMID- 8364323 TI - Home administration of intravenous antibiotics to children with cystic fibrosis. PMID- 8364324 TI - Analysis of the concept of holism within the context of nursing. AB - There is a need to define the term holism within the context of nursing in order to provide a common basis for practice. This article uses concept analysis and concept reassurance to clarify the use and meaning of the word holism. PMID- 8364325 TI - Ethical and legal issues in suicide. AB - Nurse-patient encounters are influenced by the law and by morality. These frequently overlap and hold certain principles in common, such as justice and rights. Despite such close connections, the law and morality do not necessarily correspond. The difficulty in and complexity of reaching the right and just decision in the healthcare setting often highlight this. PMID- 8364326 TI - Nurse-aid management of oral and maxillofacial emergencies. AB - Oral and maxillofacial emergencies can be very alarming and distressing to patients. This article introduces nurse aiders to the oral and maxillofacial specialty and explains the management of some oral and maxillofacial emergencies. PMID- 8364327 TI - American monitoring: standard and state of the art. AB - Monitoring of the anesthetized patient, the anesthesia machine, and the patient machine interface is an essential component of anesthetic practice in order to prevent anesthetic-related injuries resulting from equipment failure or human error. While the optimal monitor to detect anesthetic problems (hypoxia, esophageal intubation, hemodynamic compromise, for example) is unclear at present, American standards require continuous presence of qualified personnel who evaluate patient oxygenation, ventilation, circulation, and temperature. A common monitoring array includes electrocardiogram, autosphygmomanometer, pulse plethysmography/oximetry, stethoscope, anesthetic gas analyzer, thermistor, and nerve stimulator. The role of emerging technologies, including transesophageal echocardiography, automated electrocardiographic analysis of ST segments, transcranial Doppler, and transcranial near infrared spectroscopy are discussed. PMID- 8364328 TI - [Transesophageal echocardiography for evaluating left ventricular function]. AB - By means of transesophageal echocardiography it is now possible to assess and to monitor left ventricular function during anesthesia and surgery. Furthermore, the determinants of the left ventricular function (preload, afterload and contractility) can also be evaluated in real time. Based on this information, a specific therapy can be started immediately should ventricular function become inadequate. In addition to global function, regional ventricular function can be analyzed at the same time. The detection of regional wall motion abnormalities can be most helpful for anesthetic management of patients with coronary heart disease and for the diagnosis of intraoperative myocardial ischemia. PMID- 8364329 TI - [Monitoring the right ventricle: methods and relevance]. AB - For long, the right ventricle (RV) has been looked upon as a passive conduit of blood, which does not contribute to overall myocardial performance. While this is true under physiological conditions, it has been recognized only recently that an intact RV may be of crucial importance for the maintenance of cardiocirculatory stability under pathophysiological circumstances, e.g. in patients with increased pulmonary vascular resistance (PVR). Hence, several techniques have been developed to monitor RV function in these patients. With respect to the monitoring of RV preload, the validity of parameters based on pressure measurement (e.g. central venous pressure, RV end-diastolic pressure) is limited by the nonlinearity of the RV pressure-volume relationship, changes of RV compliance (e.g. ischemia, drugs), and changes of intrathoracic pressure. The measurement of RV end-diastolic volume (RVEDV) or size provides a more accurate estimation of true RV fiber preload and is currently performed using the fast response thermodilution technique. The exact quantitation of RV afterload requires the continuous assessment of RV pressure, geometry and wall thickness, which is not possible in the clinical setting. Mean pulmonary artery pressure (PAP and PVR may roughly reflect actual RV afterload under physiological conditions. However, neither PAP nor PVR take into account changes of afterload due to changes of RV size. With respect to RV contractility, none of the techniques presently available for its measurement is both valid and suitable as a tool for clinical monitoring. PMID- 8364331 TI - [Synopsis of the newest regulations for hemotherapy: consequences for physicians and hospital insurance]. PMID- 8364330 TI - Blood pressure versus blood flow. AB - The pressure-volume diagram of the left ventricle is fundamental to understanding the mechanics of contraction and its modification by disease, drugs and anaesthetics. For monitoring patients perioperatively, we advocate variables derived from the pressure-volume diagram: cardiac output to monitor circulatory failure, pulmonary capillary wedge pressure to monitor the acute state of left ventricular filling and echocardiography to determine the chronicity and severity of chronic heart failure. Use of the pressure-volume diagram shows that whenever arterial pressure is raised by the use of vasoconstrictor agents, the flow of blood to the tissues is impaired. In patients in whom the heart is damage or failing, this adverse effect of raising arterial pressure causes further deterioration of circulatory failure and flow. In view of the prime need of the body tissues for blood flow, together with oxygen and substrates, it is advocated that vasoconstricting agents should not be used to maintain arterial pressure in the perioperative period. Plasma expansion and control of posture are preferred methods for maintaining the circulation. If circulatory failure continues in the presence of a high filling pressure of the left ventricle (wedge pressure), drugs combining positively inotropic and vasodilator properties are advocated. PMID- 8364332 TI - Accuracy of blood sampling through central venous lines in intensive-care unit patients. AB - OBJECTIVE: In intensive-care unit (ICU) patients it is common practice to sample blood from central venous lines (CVL). This study was designed to answer the question on how much blood has to be aspirated through the CVL before the actual blood sample is taken to get accurate laboratory findings. DESIGN AND SETTING: Simultaneous blood samples from a peripheral vein (intraindividual control) and 5 ml portions from a CVL up to 25 ml were analyzed. PATIENTS: 5 patients of an internal ICU participated in the study. RESULTS: For the analyzed 24 different parameters it could be shown that after aspirating 10 ml of blood, the results are comparable to analyses from peripheral vein samples. CONCLUSIONS: Although blood sampling from a CVL--after aspiration of 10 ml blood--results in correct laboratory analyses, this procedure leads to a greater amount of blood loss and, hence, cannot be recommended in long-term ICU treatment. PMID- 8364333 TI - Posttransfusional changes of 2,3-diphosphoglycerate and nucleotides in CPD-SAGM preserved erythrocytes. AB - BACKGROUND: Posttransfusional changes of preserved red blood cells can influence the oxygen equilibrium curve which is mainly affected by the concentration of erythrocyte 2,3-diphosphoglycerate (DPG). MATERIAL AND METHODS: The regeneration kinetics of DPG and nucleotides (ATP, ADP, AMP, GTP, GDP) was determined over a period of 0-48 h in surgically treated patients following transfusion of DPG depleted packed red cells stored for 14 days in CPD-SAGM. RESULTS: 3 h after transfusion the DPG levels raised up to 40% of the patients' prior DPG concentrations. Complete regeneration of the DPG concentrations occurred 36-48 h after transfusion. Changes in the nucleotide pattern indicate, after a temporary decrease of ATP and GTP levels (after 10-30 min) and an activation phase (after 3 12 h), the full regeneration of these parameters 24-48 h after transfusion. CONCLUSIONS: The regeneration kinetics of DPG should be taken into consideration for transfusions with blood units stored for more than 14 days, especially in patients with reduced compensatory mechanisms (coronary and cerebral scleroses, pacemaker, etc.) and large transfusion volumes. PMID- 8364334 TI - Assessment of the Fc function in human immunoglobulins for intravenous administration. Multicenter study of the section 'Blood plasma Constituents' of the German Association for Transfusion Medicine and Immunohematology (DGTI). AB - BACKGROUND: The working group 'Blood plasma Constituents' of the DGTI has carried out a multicenter study with human immunoglobulins for intravenous administration (IVIG). The aim of the ring study was the determination of the reproducibility of the IVIG Fc function method proposed for the European IVIG monograph. MATERIAL AND METHODS: Eight laboratories from Europe participated in this ring study. The test of Fc function was carried out according to a standardized procedure. RESULTS: The results showed good consistency between the participating laboratories. The reproducibility of the method showed coefficients of variation of 5-10%. CONCLUSIONS: All commercial IVIG preparations met the requirement of the Fc function of > or = 80% in relation to the Fc function of the standard, an immunoglobulin preparation for intramuscular (i.m.) administration. PMID- 8364335 TI - [Comments on HIV antigen screening of blood donors]. PMID- 8364336 TI - Uncovering the ethic of care. PMID- 8364337 TI - The name of the journal "Praxis" becomes more than it appears. PMID- 8364338 TI - Nursing: towards a positive future. PMID- 8364339 TI - The experience of parenting a child with glue ear. PMID- 8364340 TI - Lessons from a cervical screening programme: are they transferable? PMID- 8364341 TI - Playgroup facilitation. PMID- 8364343 TI - The development of a community centre: the Rongotea Community Centre Incorporated Society. PMID- 8364342 TI - Women and HIV/AIDS: a literature review. PMID- 8364344 TI - Exemplar. PMID- 8364345 TI - A gut reaction. PMID- 8364346 TI - A study of relapses in subjects with mood disorder on lithium treatment. AB - In a sample of 213 mood disorder subjects on long-term lithium treatment, we analyzed the recurrence indices of relapses during the prophylactic treatment period. The differences found in the recurrence rates were due to the current age and age of onset, duration of illness and polarity of the probands. The patients with personality disorders showed the worst relapse indices and could represent a group of mood disorder subjects with a bad outcome of lithium treatment. PMID- 8364347 TI - Differential effects of the enantiomers R(-) and S(+) oxaprotiline on major endogenous depression, the sleep EEG and neuroendocrine secretion: studies on depressed patients and normal controls. AB - The effects of the optically active enantiomers of oxaprotiline (OXP), R(-) OXP and S(+) OXP, on depressive symptomatology and the sleep EEG were investigated in two separate exploratory studies. In addition, the neuroendocrine profile of both compounds was characterized in normal controls. In the patients treated with a daily oral dose of 150 mg S(+) OXP we found a Hamilton depression score that decreased from 29.1 +/- 1.8 (SEM) on day 0 to 14.7 +/- 3.2 on day 28 (P < 0.01). Six patients were judged to be full responders (HAMD score 0-7 points), three were improved (HAMD score 8-15) and four were nonresponders (HAMD score > 16). The therapeutic effect achieved with 150 mg R(-) OXP daily was less pronounced: the HAMD score decreased from 27.8 +/- 2.5 on day 0 to 19.4 +/- 3.2 on day 28 (P < 0.05). There were two full responders, one improved patient and seven nonresponders. The sleep EEG scoring revealed a marked suppression of REM sleep among patients treated with S(+) OXP but not with R(-) OXP. In the normal controls, a single oral dose of 75 mg S(+) OXP prompted an increase in the secretion of cortisol and growth hormone, whereas 75 mg R(-) OXP did not. Neither enantiomer influenced the secretion of testosterone or prolactin. PMID- 8364348 TI - Time course of improvement under antidepressant treatment: a survival-analytical approach. AB - A meta-analysis of an earlier multicenter, double-blind efficacy study comparing placebo, oxaprotiline and amitriptyline was performed in order to test the survival-analytical approach in modelling the onset of improvement and response to treatment with antidepressants. The sample consisted of moderately depressed male (n = 154) and female (n = 275) patients (aged 17-73), diagnosed according to DSM-III criteria for major depression. Of these, 120 were treated with oxaprotiline, 120 with amitriptyline and 189 with placebo. Efficacy criteria were Hamilton Depression (HAMD) and Anxiety (HAMA) and Zung Self-Rating scales. Up to eight ratings over a period of 40 days were available for analysis. The results showed that the sensitivity in discriminating between groups was substantially enhanced through the inclusion of drop-outs and consideration of the effect of time to withdrawal from the study due to lack of improvement. Withdrawal from the trial due to inefficacy occurred earliest under placebo (50% within the first 8 days), whereas less than 40% dropped out within the first 12 days under active treatments. The most interesting and unexpected finding of the analysis was that the time course of improvement among responders was independent of the treatment modality, and thus identical in all three groups. Specifically, the efficacy of any of the given treatments was reflected only by the total number of responders or nonresponders. Once triggered, the time course of recovery from illness becomes identical to that of spontaneous remissions as observed, for example, under placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364349 TI - Effects of valproate on early and late potassium currents of single neurons. AB - The effects of valproate sodium (VPA) on potassium currents were tested in identified neurons of the snail Helix pomatia. VPA was extracellularly and intracellularly applied. VPA (i) had no effects on the current-voltage relation of the early potassium outward current (IA), (ii) shifted the steady state inactivation function of IA to more positive potentials, (iii) increased the amplitude of the late potassium outward currents. It is suggested that the extrasynaptic effects on potassium currents markedly contribute to the antiepileptic and antimanic effects of VPA. PMID- 8364350 TI - A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. The Lilly European OCD Study Group. AB - We have studied the effect of three fixed daily doses of fluoxetine in patients with obsessive-compulsive disorder (OCD) diagnosed according to DSM-III-R. Two hundred and fourteen patients were evaluated in an 8-week double blind, placebo controlled study. A statistically significantly greater number of fluoxetine treated patients achieved the prospectively defined criteria for clinical response when compared to placebo treatment. There was a statistically significant overall difference in the PGI rating of symptom change (P = 0.045) and a marginally significant difference (P = 0.089) in the CGI severity rating between groups. Pairwise comparison against placebo showed a marginally statistically significantly greater improvement (P = 0.059) in Y-BOCS-Total score for patients receiving fluoxetine 60 mg daily, and a significantly higher response rate in patients receiving fluoxetine 40 mg or 60 mg daily (P < 0.05). One hundred and sixty one patients continued to a 16-week extension evaluation. There was no significant difference in the rate of reporting of any individual adverse event between placebo and fluoxetine, and the rate of discontinuation due to adverse events was low (< 6% in each study phase). This study supports the growing evidence for the safety and efficacy of fluoxetine in the treatment of OCD. PMID- 8364351 TI - Impact of neuropharmacology in the 1990s--strategies for the therapy of depressive illness. Task Force of the Collegium Internationale Neuro Psychopharmacologicum (CINP). PMID- 8364352 TI - Evaluation of TSH and prolactin responses to TRH as predictors of the therapeutic effect of ECT in depression. AB - In a group of 42 unipolar depressed patients with melancholia the thyrotropin (TSH) and prolactin (PRL) responses to TRH were studied in relation to the clinical response to an ECT course. Patients were categorized as responders or nonresponders using as criterion a 50% reduction in the Hamilton Rating Scale for Depression score. Comparison between responders and nonresponders with respect to the TSH and PRL responses to TRH did not reveal any significant differences. Thus, TSH and PRL responses were not proved to have a predictive value for the therapeutic ECT response in melancholia. PMID- 8364353 TI - Effects of fluoxetine given chronically on the responsiveness of 5-HT receptor subpopulations to their agonists. AB - The effect of chronic treatment (5 and 10 mg/kg i.p., twice daily, 14 days) with fluoxetine (FLU), an antidepressant drug which selectively inhibits the reuptake of 5-hydroxytryptamine (5-HT), on the responsiveness of 5-HT receptor subpopulations to their agonists in rats and mice was examined. FLU had no effect on the hypothermia (in mice) and the behavioural syndrome (in rats) induced by 8 OH-DPAT (a 5-HT1A agonist). The m-CPP-induced hypothermia in mice (a 5-HT1B effect) was increased by FLU given chronically. FLU in a single dose decreased that effect. FLU given chronically attenuated the m-CPP-induced hypoactivity in rats (a 5-HT1C effect). The effects mediated by 5-HT2 receptors (L-5-HTP-induced head twitches in mice; fenfluramine-, m-CPP- and TFMPP-induced hyperthermias in rats) were reduced by chronic FLU. The above results indicate that FLU given chronically has no effect on the responsiveness of 5-HT1A receptors, increases the responsiveness of 5-HT1B receptors and decreases those of 5-HT1C and 5-HT2 receptors. PMID- 8364354 TI - Effect of acetyl-L-carnitine treatment on brain adenylate cyclase activity in young and aged rats. AB - The aim of the present study has been to evaluate the effect of acetyl-L carnitine (ALCAR) on brain adenylate cyclase (AC) activity in adult and aged rats. In in vitro studies, ALCAR (1, 10 and 100 microM) did not exert any effect on frontal cortex basal AC activity. Acute and subchronic administrations of ALCAR were carried out in 4- and 25-month-old male Fisher rats and AC activity was determined in rat frontal cortex under both basal and stimulated conditions. The acute treatment of young rats with ALCAR (100 and 500 mg/kg s.c.) did not affect AC activity, whereas the subchronic administration of 250 mg/kg s.c. ALCAR enhanced the stimulation of AC by carbamylcholine (CCh), norepinephrine (NE) and dopamine (DA), without affecting the basal AC activity. Basal AC activity in old rats was lower than in young rats and was not modified by acute and subchronic ALCAR administration. Moreover, the response of the enzyme to CCh, NE and DA was potentiated by the subchronic administration of ALCAR. The concentration-response curve of CCh stimulation of AC activity in ALCAR-treated rats is shifted to the left in both young and aged rats. We conclude that ALCAR, subchronically administered, is able to enhance receptor-stimulated AC response in frontal cortex of both young and aged rats. PMID- 8364355 TI - Phytochrome A null mutants of Arabidopsis display a wild-type phenotype in white light. AB - Phytochrome is a family of photoreceptors that regulates plant photomorphogenesis; the best-characterized member of this family is phytochrome A. Here, we report the identification of novel mutations at three Arabidopsis loci (fhy1, fhy2, and fhy3) that confer an elongated hypocotyl in far-red but not in white light. fhy2 mutants are phytochrome A deficient, have reduced or undetectable levels of PHYA transcripts, and contain structural alterations within the PHYA gene. When grown in white light, fhy2 mutants are morphologically indistinguishable from wild-type plants. Thus, phytochrome A appears to be dispensable in white light-grown Arabidopsis plants. fhy2 alleles confer partially dominant phenotypes in far-red light, suggesting that the relative abundance of phytochrome A can affect the extent of the far-red-mediated hypocotyl growth inhibition response. Plants homozygous for the recessive fhy1 and fhy3 mutations have normal levels of functional phytochrome A. The FHY1 and FHY3 gene products may be responsible for the transduction of the far-red light signal from phytochrome A to downstream processes involved in hypocotyl growth regulation. PMID- 8364357 TI - Afterword for the paperback edition of The American Way of Birth. PMID- 8364356 TI - Transgenic tobacco plants expressing the geminivirus BL1 protein exhibit symptoms of viral disease. AB - Bipartite geminiviruses, such as squash leaf curl virus (SqLCV), encode two movement proteins (MPs), BR1 and BL1, that are essential for viral movement in and subsequent infection of the host plant. To elucidate the biochemical functions of these MPs and define their respective contributions to viral infection, we have generated transgenic Nicotiana benthamiana plants expressing SqLCV BR1 and BL1. Transgenic plants expressing BR1 or a truncated BL1 were phenotypically indistinguishable from wild-type N. benthamiana. In contrast, transgenic plants expressing full-length BL1, alone or in combination with BR1, were strikingly abnormal both in their growth properties and phenotypic appearance, with leaves that were mosaic and curled under, thus mimicking typical SqLCV disease symptoms in this host. BL1 was localized to the cell wall and plasma membrane fractions, whereas BR1 was predominantly in the microsomal membrane fraction. These findings demonstrate that expression of BL1 in transgenic plants is sufficient to produce viral disease symptoms, and they further suggest that BL1 and BR1 carry out distinct and independent functions in viral movement. PMID- 8364358 TI - What is your recommendation at the Farm Midwifery Clinic about childhood immunizations? PMID- 8364359 TI - Entry level midwifery skills list revision #3. PMID- 8364360 TI - Verbal arts: survival skills for midwives. PMID- 8364361 TI - The Mother Self-Determination Act. PMID- 8364362 TI - A Canadian's thoughts. PMID- 8364363 TI - Mandatory breastfeeding questioned. PMID- 8364364 TI - An extraordinary breastfeeding experience. Interview by Ina May Gaskin. PMID- 8364365 TI - Interview with Anna Meenan, MD. Interview by Ina May Gaskin. PMID- 8364367 TI - Mediterranean diet and digestive precancerous lesions. PMID- 8364366 TI - Faecal occult blood tests in adenoma detection. PMID- 8364368 TI - Cancer prevention programmes in health promotion. PMID- 8364369 TI - Potentially malignant lesions and conditions of the mouth and oropharynx: natural history--cellular and molecular markers of risk. PMID- 8364370 TI - General overview of gastrointestinal precancer. PMID- 8364371 TI - Precancer lesions of oesophageal adenocarcinoma: phenotypic markers and growth factors. PMID- 8364372 TI - Oesophageal cancer: prospects for primary prevention. PMID- 8364373 TI - Epidemiology and pathology of precancerous lesions of the stomach. PMID- 8364374 TI - Diet and precancerous lesions of the stomach. PMID- 8364375 TI - Mechanisms of gastric carcinogenesis. PMID- 8364376 TI - Primary prevention of gastric precancerous lesions. PMID- 8364377 TI - The National Polyp Study. PMID- 8364378 TI - Rectal cell proliferation as an intermediate biomarker of risk of colorectal cancer. PMID- 8364379 TI - Intragastric mutagens and lowered anti-oxidant defence as risk factors for gastric cancer. PMID- 8364380 TI - Diet and the adenoma-carcinoma sequence. PMID- 8364381 TI - Interactive technology: the time is now. PMID- 8364382 TI - Grant funding to support staff development activities. PMID- 8364383 TI - Seven skills for successful speaking. PMID- 8364384 TI - Self-directed learning. To be a great facilitator, don't follow these steps. PMID- 8364385 TI - Organizational development: the educator's role. PMID- 8364386 TI - What's happening?! PMID- 8364387 TI - [Polarized phenomena in biological structures]. PMID- 8364388 TI - [An electrophoresis method in low density agarose gel for analyzing the chromatin condensation process]. PMID- 8364389 TI - [Toxic effects of the combined action of ionizing radiation and halogenated dibenzo-p-dioxins on mammals]. PMID- 8364390 TI - [Regulation of enzymatic oxidation of thermostable comuton from rat liver mitochondria]. PMID- 8364391 TI - [Characteristics of viruses in the BKM Y-2700 mycocinogenic strain of Cystofilobasidium bisporidii yeasts]. PMID- 8364392 TI - Control of metaphase I formation in Xenopus oocyte: effects of an indestructible cyclin B and of protein synthesis. AB - A cytological analysis was performed in order to determine how the formation of the metaphase I- and metaphase II-spindles is dependent upon p34cdc2 kinase activity and protein synthesis during the meiotic maturation of Xenopus oocytes. The p34cdc2 kinase activity increases abruptly during the prophase-prometaphase I transition, then drops to a minimum level at the metaphase I/anaphase I transition and further increases again until reaching a maximum stable level at metaphase II. The injection of an indestructible cyclin B into oocytes arrests the maturation process at the onset of anaphase I and prevents the re-increase of p34cdc2 activity which accompanies normal entry into metaphase II. Inhibition of protein synthesis between the germinal vesicle breakdown and the onset of metaphase I spindle induces exit from M-phase and leads to an 'interphase-like' state characterized by the organization of nuclear-like structures. In contrast, inhibition of protein synthesis at metaphase II stage does not affect the metaphase II spindle nor p34cdc2 activity, indicating that metaphase I- and metaphase II-spindles are not regulated by the same effectors. When protein synthesis is inhibited before induction of M-phase by MPF transfer, it prevents the formation of the metaphase I spindle, despite a transient elevated level of p34cdc2 activity. To dissociate the role of protein synthesis and of p34cdc2 kinase activity, the indestructible cyclin B was microinjected in the absence of protein synthesis. This allows the in vivo maintenance of a stable p34cdc2 activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364393 TI - Nuclear compartmentalization in transcriptionally activated hypothalamic neurons. AB - Transcription of cell-specific vasopressin and oxytocin genes as well as transcription of those housekeeping genes responsible for general metabolic activation and cellular hypertrophy is induced in supraoptic hypothalamic neurons by rises in plasma osmolarity. In this study, the nuclear volume, the ultrastructure of chromatin and the number and distribution of nuclear particles in the cell nuclei of supraoptic neurons of 3-month-old male Sprague-Dawley rats were analyzed after osmotically induced activation of transcription by periods of acute (1 day) and chronic (6 days) dehydration, and after halting the stimulation by rehydration of animals. The nuclear volume and the ultrastructure of chromatin were assessed on ultrathin sections. The number and distribution of nuclear particles were assessed on freeze-fracture replicas. The initial phase of osmotically induced enhancement of transcription was accompanied by an increase in nuclear volume and by a partial replacement of nuclear particles of large diameter (> 11 nm) by smaller nuclear particles. This latter change affected predominantly the nuclear periphery (0-1,000 nm from the nuclear membrane) and occurred simultaneously with a partial decondensation of chromatin clusters that may be related to chromatin unfolding. In chronically stimulated animals, the decondensation of chromatin and the replacement of large nuclear particles by smaller ones was enhanced in the nuclear periphery and was partially propagated to the interior of the nucleus. After suppression of cellular activation by rehydration of animals, the number of nuclear particles returned to control levels in the nuclear periphery while in the center of the nucleus the number of small particles decreased and the number of large particles increased as compared to control values. These results, together with the observation that in unstimulated cells the nuclear periphery and the nuclear interior differ in their composition of nuclear particles, evidence a structural and functional compartmentalization in the cell nucleus of supraoptic neurons. PMID- 8364394 TI - Sequence of the novel joints present in the amplified DNA of N-phosphonacetyl-L aspartate resistant Drosophila cells: implication on the mechanisms of amplification in these cells. AB - We have previously shown the presence, in the amplified DNA of a Drosophila cell line resistant to N-phosphonacetyl-L-aspartate (PALA), of two units of 150 kb and 120 kb respectively duplicated and amplified. The two joints (J1 and J2) linking these units as well as their respective wild-type counterparts have been sequenced. Sequence analysis indicates that a region of the Drosophila genome which corresponds to the proximal boundary of the 150 kb unit is common to both joints. In addition to this common region, the J1 junction possesses a 26 nucleotide sequence belonging to the J2 junction. This indicates that the J2 junction was the first formed, and that J1, therefore, results from recombination between J2 and a region of the wild-type genome 120 kb distal to J2. Sequence analysis also reveals that the joints result from illegitimate recombination between unrelated regions. AT-rich sequences, strand bias composition and putative topoisomerase I and II sites were found in at least one of the two parental sequences involved in the formation of the joints. On the basis of these results we can hypothesize that after two illegitimate recombinations between sister chromatids, leading first to J2 and then to J1, the amplification may have arisen by a series of homologous (unequal crossing-over) or illegitimate recombinations, or by an intrachromosomal rolling circle. PMID- 8364395 TI - The elementary RNP fiber--not the higher order structure--determines the all-or none disintegration behaviour of Balbiani ring pre-messenger RNP particles upon RNase A treatment. AB - Balbiani ring premessenger ribonucleoprotein (RNP) particles are built from a 7 nm RNP fiber which is tightly folded into a ring-shaped RNP ribbon. Isolated particles are known to disintegrate in all-or-none fashion upon RNase A treatment. In the present study we investigated whether this mode of disintegration is dependent on an intact particle structure or is inherent in the 7-nm fiber. When treated at low ionic strength, the Balbiani ring (BR) particles lost their higher order structure and the 7-nm fiber was unpacked, as evidenced by sucrose gradient sedimentation and electron microscopy. When treated with RNase A, unfolded as well as intact particles disintegrated in the all-or-none fashion, with similar kinetics and without apparent intermediates. Proteinase K treatment, however, obliterated this pattern: the protein-free particle RNA degraded progressively. As the typical disintegration pattern of the particles was not altered by unfolding, but was lost by deproteinization, the all-or-none mode of disintegration is likely to be a property of the 7-nm RNP fiber. PMID- 8364396 TI - Ultrastructural cytochemistry of the nucleus and nucleolus in growing rabbit oocytes. AB - Ultrastructural changes of the germinal vesicle during the growth of rabbit oocytes were studied by means of light and electron microscopy, 3H-uridine autoradiography, Ag-NOR staining and E-PTA staining. Particular interest was paid to the nucleologenesis and condensation of chromatin. In contrast to other mammalian species, chromosome condensation in rabbit oocytes occurred concomitantly with rRNA synthesis-dependent nucleolar compaction and preceded nuclear envelope breakdown and resumption of meiosis. PMID- 8364397 TI - Culture of human preovulatory granulosa cells: effect of extracellular matrix on steroidogenesis. AB - Human luteal granulosa cells, harvested from preovulatory follicles during in vitro fertilization attempts, were cultured in a serum-precoated substratum ('serum cells') or on a collagen matrix ('collagen cells'). Concerning the 'serum cell' model, E2 secretion was very low in the absence of androgen; when androstenedione was added to the culture medium, cells secreted 180 +/- 52 pmol/ml/24 h of estradiol, 440 +/- 78 pmol/ml/24 h of testosterone and lower quantities of estrone and estriol. Follicle stimulating hormone induced a significant increase in estradiol and estriol, while the secretion of the other steroids was not altered. The secretion of progesterone was 3.15 +/- 1 nmol/ml/24 h and significantly enhanced by luteinizing hormone (+ 95%; P < 0.01). The secretions of 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were low and not modified by luteinizing hormone. 'Collagen cells', in basal conditions, showed an increased secretion of estradiol (+ 50%, P < 0.05), became rounded and were less responsive to gonadotropins when compared with 'serum cells'. Thus, the use of a collagen matrix, similarly to gonadotropins, stimulated granulosa cell steroidogenesis in relation to modifications of cell shape. The higher responsiveness of serum cells to gonadotropins makes this model more suitable for physiological and pharmacological studies than the collagen one. PMID- 8364398 TI - Endocytosis of alpha 1-acid glycoprotein variants by human monocytic lineage cells. AB - Human alpha 1-acid glycoprotein (AGP or orosomucoid) is a major glycoprotein of plasma. AGP can be separated on immobilized concanavalin A into three variants bearing none (AGP A), one (AGP B) or two (AGP C) biantennary glycans. In this paper, we show, using flow cytometry and confocal microscopy, that AGP C which is eluted from concanavalin A with mannose, binds to human monocytes, monocyte derived macrophages as well as human promonocytic cell lines such as THP1 or U937. Conversely HL60, a promyelocytic cell line, does not express the surface AGP C binding protein. AGP C is internalized and degraded with an efficiency depending on the state of differentiation of these cells. In contrast, AGP A which is not recognized by concanavalin A, does not bind to any of these cells. PMID- 8364399 TI - The effects of structural analogs of putrescine on proliferation, morphology and karyotype of glioblastoma cells in culture. AB - In a previous study, we identified regions on the surface of tumor cells which act as acceptor sites for putrescine (Put) and studied the competition between structural analogs of Put (N,N'-tetramethyl-alpha,omega-diaminoalkanes) and Put bound to latex microspheres. A chain of four to seven carbons was necessary for inhibition of Put-latex binding to the cell surface of human glioblastoma (U251) cells. We show here that under the experimental conditions, N,N'-tetramethyl-1,4 butanediamine and N,N'-tetramethyl-1,7-heptanediamine exhibit an antitumor effect. In a first step (1-48 h after treatment), cells exposed to these compounds show large intracellular vacuoles. We failed to detect any acid phosphatase activity in these intracellular structures revealing that they were not lysosomes. Electron microscopy observations argue for the conclusion that these vacuoles are an hypertrophy of the endoplasmic reticulum (ER) and/or of the Golgi vesicles. Our hypothesis is that this typical effect of the analogs reveals that ER could be a physiological target of endogenous polyamines. At a later stage (6 days after treatment), the cells undergo morphological and biochemical changes: thin and long expansions characterize the cells and the GFA protein is overexpressed. Correlated to both these effects, karyotypic modifications are found in chromosomes 3 and 6. These changes evoke a differentiation of the treated cells. The work provides evidence that N-methylated polyamine analogs taking the place of endogenous putrescine demonstrate a hopeful antitumor effect. PMID- 8364400 TI - Interaction between Aspergillus fumigatus and basement membrane laminin: binding and substrate degradation. AB - Aspergillus fumigatus, the causative agent of human aspergillosis, binds to and degrades basement membrane laminin. Using immunoelectron microscopy, laminin binding appeared to be associated with the cell wall expansions of resting conidia, and progressively extended to the outer electron dense layer of the conidial wall during the germination process. Labeling of thin sections revealed numerous binding sites in the cytoplasm, whereas the inner cell wall and the plasma membrane were not labeled. Attachment of A fumigatus conidia on microtiter plates coated with laminin and its fragments P1 and E8 was also investigated. Conidia cells showed good adhesion to wells coated with laminin. As indicated by inhibition experiments, the interaction was specific and fragment P1 represented the major binding site on the laminin molecule. In addition, since A fumigatus produced an extracellular serine protease, we determined the susceptibility of laminin to this enzyme. We demonstrated that protease extract was capable to degrade laminin in solution as well as in tissue sections. The laminin cleavage products were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All the three chains were extensively degraded within 1 h. Treatment of the crude protease extract with the enzyme inhibitors, phenylmethylsulfonyl-fluoride and chymostatin, blocked the degradation of laminin, indicating a chymotrypsin-like serine protease activity. Immunofluorescence microscopy of cryostat sections of mouse and rat kidneys treated with the protease extract showed widespread loss of laminin epitopes from basement membranes. Enzyme treatment also removed immunoreactivity from lungs as observed after immunoperoxidase performed on paraffin sections. Binding and proteolytic degradation of laminin may together facilitate initial interaction of A fumigatus with the host tissues. PMID- 8364401 TI - In vitro attachment of Pneumocystis carinii from mouse and rat origin. AB - The attachment of Pneumocystis carinii to lung cells could play a role in the pathophysiology of P carinii pneumonia. The trophozoite attaches to type I alveolar epithelial cells. Physical, chemical, and extracellular matrix factors, involved in the mouse-or rat-derived P carinii attachment to fibroblastic cells in culture, were examined using a new model of in vitro adherence. The development of parasite filopodia penetrating deeply the host cell cytoplasm was observed using transmission electronic microscopy. Killed P carinii organisms were unable to attach to cultured cells. Also, parasites were unable to attach to killed target cells. The P carinii in vitro attachment was partially inhibited by cytochalasin B. In contrast, the parasite attachment was not affected when the target cell cytoskeleton was altered. In our work conditions, sialic acids were not involved in the attachment process. Present results showed that fibronectin (Fn) plays a role in the parasite attachment, and suggest that a specific Fn binding receptor is present at the surface of mouse-derived P carinii organisms. PMID- 8364402 TI - Association of the actin cytoskeleton with glass-adherent proteins in mouse peritoneal macrophages. AB - When mouse peritoneal macrophages adherent to glass surface were removed by treatment with triethanolamine and Nonidet P-40, fine thread structures of unique loops were left behind on glass at the sites of cell adhesion. To examine the ultrastructural relationship between such looped threads and cytoskeletal components in glass-adherent macrophages, we successfully used the 'zinc method' to remove most of the cytoplasm including nuclei and to expose the cytoskeleton associated with the ventral plasma membrane. The cytoskeleton was seen to be mainly composed of actin filaments forming dense networks. The network contained scattered star-like foci from which actin filaments radiated. When the ventral plasma membrane-cytoskeleton complex was further treated with Nonidet P-40, the membrane was dissolved to expose the glass surface with actin foci persisting on glass. When the complex was removed by further treatment with Nonidet P-40 and DNase I, the looped threads became visible. Confocal laser microscopy of glass adherent macrophages stained with fluorescent phalloidin showed the preferential distribution of F-actin in the ventral cytoplasm along the plasma membrane, where intense fluorescent spots were also scattered. Confocal interference reflection microscopy revealed densely populated dark dots and striae of focal contact, which corresponded in overall distribution to actin foci and looped threads. These observations suggest that actin cytoskeleton is closely associated with looped threads to reinforce cell adhesion to glass. PMID- 8364403 TI - The in vitro destruction of rumen fluid carotenoids by plant lipoxygenases. AB - An ability to destroy carotenoids in the rumen of cattle may be an effective method of limiting their absorption from the small intestine which, in turn, is likely to result in reduced adipose tissue colour. Plant lipoxygenases are well known for their ability to bleach beta-carotene. As lutein is the major carotenoid present in most forage grasses, we have investigated the bleaching of lutein as well as beta-carotene by lipoxygenase isolated from soybeans. In vitro studies, using micellar preparations of carotenoids, indicated that lutein was rapidly oxidised and that the progress of the reaction was similar to that observed for beta-carotene. The polyunsaturated fatty acid linoleate was essential. When bovine rumen fluid was used as a source of carotenoid for in vitro studies with preparations of lipoxygenase, a rapid decrease in carotenoid and chlorophyll concentrations was observed, again requiring the addition of linoleic acid. The direct addition of soya flour to bovine rumen fluid resulted in the effective bleaching of the pigments without the inclusion of linoleate. When compared with flours from a variety of other plant sources, soya flour was most effective. The inclusion of dietary sources of lipoxygenase may be an effective method for controlling carotenoid uptake in certain ruminant species. PMID- 8364404 TI - A comparison of beta-carotene-splitting activity isolated from intestinal mucosa of pasture-grazed sheep, goats and cattle. AB - The in vitro enzymatic conversion of beta-carotene to retinal by partially purified preparations from the intestinal mucosa of sheep, goats and cattle was demonstrated. At pH 7.8 and 37 degrees C, this enzyme from sheep, goats and cattle displayed Michaelis-Menten type kinetics with a Vmax (nmol substrate split/mg protein/h) of 0.21, 0.27, and 0.04 and an apparent Km of 4.66 x 10(-6) M, 13.4 x 10(-6) M and 1.27 x 10(-6) M respectively. Maximal reaction was obtained by addition of an appropriate combination of detergent and bile salt, sodium dodecyl sulphate and egg lecithin. The cattle enzyme was inhibited by sodium glycocholate. The activity of sheep enzyme was higher (P < 0.05) than that of goats and cattle. The measured activity of the preparations from sheep, goats and cattle grazed on the same pasture reflected their contents of the reaction product, retinol, in the liver. PMID- 8364405 TI - Involvement of calcium-dependent cysteine protease in fibronectin-induced chemotactic migration of NIH-L13 fibroblasts. AB - Fibronectin (FN)-induced chemotactic migration of NIH-L13 fibroblasts was suppressed by the inhibitors of cysteine proteases, leupeptin (IC50 = 3 microM), and the epoxysuccinyl derivatives [E-64c (10 microM), SUT-8801 (45 microM), and SUT-8818 (28 microM)], but hardly by phenylmethanesulfonyl fluoride (> 1 mM) and 1-tosyl-amido-2-phenylmethyl chloromethyl ketone (> 1 mM). E-64d, a membrane permeant derivative of E-64c, was much more effective (IC50 = 4 microM) than E 64c in preventing the cell migration. Furthermore, the FN-induced cell migration was blocked partially with EGTA and was reversed by addition of Ca2+ ion. These results suggest that intracellular Ca(2+)-dependent cysteine proteases may be involved in the FN-induced chemotactic migration of NIH-L13 fibroblasts. PMID- 8364406 TI - The effect of contraceptive steroids on plasma lipoprotein metabolism in female rats (II). AB - In order to investigate the effects of two contraceptive steroids given orally, which contain ethinyl estradiol in combination with different types and doses of progestins, on plasma lipoprotein metabolism, rat groups named according to progestin components were designated as short-and long-term groups of norethisterone acetate and levonorgestrel at low-and high-doses. At the end of the experiments, plasma triglyceride, phospholipid, apolipoprotein A1 and B, LDL , HDL-, HDL2- and HDL3-cholesterol levels and hepatic lipase activity were measured. When compared to controls, phospholipid and LDL-cholesterol were increased in all groups; triglyceride levels were also increased in all short term groups, but only in low-dose norethisterone and high-dose levonorgestrel of long-term groups. HDL- and HDL3- cholesterol were decreased in all groups, except in low-dose levonorgestrel groups, but HDL2-cholesterol were lower only at high doses and long period. In short-term, an increase in apolipoprotein A1 levels was significantly important at high doses; in long-term apolipoprotein A1 was increased at low doses, while decreased at high doses. Apolipoprotein B was elevated only in long-term high dose of norethisterone acetate group. Hepatic lipase activity was increased in long-term high-dose of levonorgestrel group, whereas decreased in all other groups. In conclusion, the data presented was interpreted that the effects of these combinations used in the study on plasma lipoprotein metabolism may be related to the changes observed in hepatic lipase activity. PMID- 8364407 TI - Isolation and characterization of the ND2 polypeptide of the bovine energy transducing NADH-ubiquinone oxidoreductase (complex I). AB - The M(r) 30,000 polypeptide of the hydrophobic protein fraction of the energy transducing NADH-ubiquinone oxidoreductase (complex I) of bovine heart mitochondria was identified as the ND2 gene product based on a comparison of amino acid analysis and partial N-terminal sequencing results with the known DNA sequence of ND2 (Anderson, S. et al. (1982) J. Mol. Biol. 156, 683-717). A simple purification procedure was devised for this ND2 gene product. The procedure, which is described, involves treatment of bovine complex I with a chloroform methanol (2:1 [v/v]) solution. The antiserum raised against this purified bovine ND2 gene product cross-reacted with the approximately M(r) 39,000 polypeptide extracted from the Paracoccus denitrificans membranes with chloroform-methanol (2:1 [v/v]). PMID- 8364408 TI - Protective role of metallothionein in nickel induced oxidative damage. AB - Recent studies have focussed on the role of thiol rich proteins especially metallothionein (MT) in the therapeutic interventions against oxidative damage. In our previous communication we showed that reactive oxygen species arising via Fenton's reactions are the proximal lipid oxidant during nickel-toxicity. The purpose of the present communication is to evaluate the role of zinc, cadmium or silver-metallothioneins on the protection against nickel-induced peroxidative damage. Our results demonstrate that Zn-MT provided maximum protection against nickel-induced mortality in mice and also served as an efficient antagonist in inhibiting nickel-mediated lipid peroxidation compared to Cd-MT or Ag-MT. Zn-MT also provided protection against iron (II)-ascorbate induced microsomal lipid peroxidation and reversed nickel-mediated inhibition of calcium sequenstration. We conclude that Zn-MT could serve as an excellent physiological antioxidant against nickel-mediated oxidative. PMID- 8364410 TI - Inhibition of glutamate dehydrogenase by covalent coenzyme-substrate adducts: a re-examination. AB - Covalent adducts of NAD+ with pyruvate and 2-oxoglutarate have been reported to inhibit differentially the activities of bovine glutamate dehydrogenase (GDH) towards these two oxoacid substrates, implying separate active sites. Thorough reinvestigation fails to confirm this finding, with the pyruvate adduct uniformly the more potent inhibitor of both substrate activities under several assay conditions. This suggests that bovine GDH provides amino acid dehydrogenation sites of one structural type only. Clostridial GDH, with a strong preference for oxoglutarate over pyruvate as substrate, is also more strongly inhibited by the pyruvate adduct in the oxoglutarate assay. These findings challenge the generality of the view that carbonyl substrates used in forming such adducts confer specificity for the corresponding substrate binding pocket in enzyme active sites. PMID- 8364409 TI - Duplication of secretion signal sequences is deleterious for the secretion of human interferon alpha 4 from Saccharomyces cerevisiae and Bacillus subtilis. AB - Tandem duplication of a mitochondrial import leader sequence has been shown to markedly increase the efficiency of translocation of chimaeric precursors across mitochondrial membranes to the mitochondrial matrix. The principle of leader sequence duplication was applied to the protein secretion system of the yeast Saccharomyces cerevisiae and of Bacillus subtilis. The secretion signal sequences of yeast invertase and B. subtilis neutral protease were used to direct the secretion of human interferon alpha 4. Our results show that the duplication of these N-terminal signal sequences does not enhance secretion of interferon alpha 4 in either of the cell systems studied. PMID- 8364411 TI - Regulation of the annexin Icp35 gene in transfected mammary gland cell lines. AB - We have tested the ability of the 5' flanking region of the lactogen-regulated annexin Icp35 gene to drive the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene in T-47D, HBL-100 and HC11 cells. A construct containing 1,400 bp of the 5' flanking region including the putative promoter, and the first two exons and intervening sequence showed lower activity compared with a similar construct containing only 250 bp of the 5' flanking region. This indicated the presence of negative regulatory elements in the distal 5' flanking region. Experiments were done to determine the effect of lactogens (either ovine prolactin, or human growth hormone) on the cp35 promoter using various hormone treatments, growth conditions and serum supplements. We did not observe any effect of hormones on the expression of the cp35/CAT constructs under the conditions tested. PMID- 8364412 TI - Two microassays for determination of a wide range of proteolytic activities using Azocoll as substrate. AB - Two micromethods for measuring proteolytic activity were developed. A semiquantitative assay on microtitre plates with granular Azocoll as substrate is based on the determination of the time of first appearance of pink colour, t, in the reaction mixture and proteolytic activity is expressed as 1/t. This simple, sensitive and economical method is convenient for preliminary testing of a large number of small samples with unknown proteolytic activity, such as fractions after chromatography. It speeds up considerably proteinase purification. The other test, a quantitative microassay, is a low-cost and time-saving version of the classical method which reduces material consumption and includes automated measurement of absorbance in microtitre plates by a Multiscan reader. Application of these methods are demonstrated. PMID- 8364413 TI - Calcium and dithiothreitol dependent conformational changes in beta-sheet structure of collagenase resistant fragment of human surfactant protein A. AB - Ca2+ dependent conformational change of collagenase resistant fragment (CRF) of human surfactant protein A (SP-A) was studied by measurements of the far UV circular dichroism spectrum. The spectrum was altered by Ca2+ and DTT. The beta sheet content was decreased by the addition of Ca2+ from 28.1 to 26.6%. On the other hand, the beta-sheet content was increased in the presence of dithiothreitol from 28.1 to 36.0%, and decreased by the addition of Ca2+ from 36.0 to 30.5%. The total Ca2+ concentration required for half maximal change of the ellipticity at 220 nm was estimated to be 30 microM both in the presence and absence of dithiothreitol. One of the functions of SP-A, enhancement of phospholipid uptake by alveolar type II cells, was abolished by the addition of 2 mercaptoethanol. These results strongly indicate a relationship between the conformation of CRF and SP-A functions. PMID- 8364414 TI - Comparative studies of intracellular activity, secretion and multiple forms spectra of human skin fibroblast alpha-L-fucosidase in the normaland after sucrose load. AB - Activity and multiple forms of intracellular and secreted alpha-L-fucosidases from human skin fibroblasts were studied in normal and sucrose-loaded cells- modelling intralysosomal nonhydrolyzable products' accumulation in vitro. Certain differences in secretion levels were found after sucrose load for alpha-L fucosidases from embryonal and postnatal cell lines. Different effects of sucrose load on multiple forms' spectra of the intracellular and secreted alpha-L fucosidases from embryonal and postnatal fibroblasts were revealed. PMID- 8364415 TI - Changes in intracellular potassium and thiol levels in Escherichia coli K12 under various stresses. AB - The levels of intracellular K+ and thiols were measured synchronously in E. coli cells under starvation stress and osmotic upshock,alkaline shift and cytoplasm acidification. The level of nonprotein thiols increased in response to osmotic upshock and alkaline shift but decreased under cytoplasm acidification. A positive correlation between the changes in the K+ pool and the level of nonprotein thiols was found under osmotic shock and alkaline shift. Inverse correlation between these parameters was observed after the acidification of cytoplasm. It is supposed that there is a tight relationship between the levels of K+, nonprotein thiols and intracellular pH. PMID- 8364416 TI - Characterization of platelet agglutinating protein p37 purified from the plasma of a patient with thrombotic thrombocytopenic purpura. AB - We have previously reported the purification of a 37 KDa platelet agglutinating protein (PAP p37) from the plasma of a patient with thrombotic thrombocytopenic purpura and have shown that it is present in a subset of TTP patients, but absent in normal subjects. In this study, we would like to report some of the physico chemical and immunological properties of this protein. The native molecular weight of PAP p37 from gel filtration was found to be 36,000, which is in agreement with denatured molecular weight (37,000), determined by SDS- polyacrylamide gel electrophoresis under both reducing and non-reducing conditions. The values of Stoke's radius (25A), diffusion coefficient (8.59 x 10( 7)cm2/s) and frictional ratio (1.13), determined by molecular sieve chromatography, suggest that the native protein is compact and globular. The purified protein has an S20,w of 3.5s. Preliminary carbohydrate analysis suggested that p37 is a glycoprotein and contained about 11% neutral sugars and 6.6% sialic acid. Amino acid analysis indicated that the protein is relatively rich in aspartate and serine and has low cysteine, methionine and tryptophan contents. In dot immunobinding ELISA assay, PAP p37 did not react with antibodies to thrombospondin, fibrinogen, fibronectin, plasminogen and von Willebrand factor. Our results suggest that PAP p37 is a single polypeptide compact and globular glycoprotein and is immunologically not related to the aforementioned proteins. PMID- 8364417 TI - Feedback and delays in neurological diseases: a modeling study using dynamical systems. AB - Numerous regulatory mechanisms in motor control involve the presence of time delays in the controlled behavior of the system. Experimentally, we have shown that an increase of the time delay in visual feedback induces different oscillations in control subjects and in patients with neurological diseases during the performance of a simple compensatory tracking task. A preliminary model is proposed to describe the oscillations observed in control subjects and in patients with neurological diseases. The influence of delays in two feedback loops are the main components of the motor control circuitry involved in this task and are studied from an analytical and physiological perspective. We analytically determine the influence in the model of each of these delays on the stability of the finger position. In addition, the influence of stochastic elements ("noise") in the modeling equation is seen to contribute qualitatively to a more accurate reproduction of experimental traces in patients with Parkinson's disease but not in patients with cerebellar disease. PMID- 8364418 TI - The kinetics of enzyme systems involving activation of zymogens. AB - A general model of zymogen activation is proposed and explicit kinetic equations for the time courses of the various species and products involved are given. These equations are valid for the whole course of the reaction and therefore for both the transient phase and the steady state. This model is sufficiently general to include mechanisms possessing one or more steps of zymogen activation besides possible steps of inhibition (reversible or irreversible) or inactivation. PMID- 8364419 TI - Langevin equation, Fokker-Planck equation and cell migration. AB - Cell migration can be characterized by two independent variables: the speed, v, and the migration angle, phi. Each variable can be described by a stochastic differential equation--a Langevin equation. The migration behaviour of an ensemble of cells can be predicted due to the stochastic processes involved in the signal transduction/response system of each cell. Distribution functions, correlation functions, etc. are determined by using the corresponding Fokker Planck equation. The model assumptions are verified by experimental results. The theoretical predictions are mainly compared with the galvanotactic response of human granulocytes. The coefficient characterizing the mean effect of the signal transduction/response system of the cell is experimentally determined to 0.08 mm/V sec (galvanotaxis) or 0.7 mm/sec (chemotaxis) and the characteristic time characterizing stochastic effects in the signal transduction/response system is experimentally determined as 30 sec. The temporal directed response induced by electric field pulses is investigated: the experimental cells react slower but are more sensitive than predicted by theory. PMID- 8364420 TI - Comparative kinetics of embryo development. AB - A model of embryo energetics was fitted to data from the literature for species as different as snails and mammals. The model is based on assumptions about energy uptake, storage and utilization. It describes the animal by two state variables: volume and energy storage. Embryo weight is taken to be proportional to volume, yolk weight to energy storage, and respiration rate to storage utilization rate. The fits were good, with minor deviations occurring only in the early phases of development. For altricial birds, good model fits were obtained, but the parameter values markedly differed from those of other species. We hypothesized that, due to an increase in energy utilization towards hatching, the temperature of the embryo increases. As a result, metabolic processes are accelerated. When this was taken into account, parameter values were obtained that correspond better with those of other animals. PMID- 8364421 TI - Stress-induced alignment of actin filaments and the mechanics of cytogel. AB - Experimental evidence suggests that anisotropic stress induces alignment of intracellular actin filaments. We develop a model for this phenomenon, which includes a parameter reflecting the sensitivity of the microfilament network to changes in the stress field. When applied to a uniform cell sheet at rest, the model predicts that for sufficiently large values of the sensitivity parameter, all the actin filaments will spontaneously align in a single direction. Stress alignment can also be caused by a change in external conditions, and as an example of this we apply our model to the initial response of embryonic epidermis to wounding. Our solutions in this case are able to reflect the actin cable that has been found at the wound edge in recent experiments; the cable consists of microfilaments aligned with stress at the wound boundary of the epithelium. These applications suggest that stress-induced alignment of actin filaments could play a key role in some biological systems. This is the first attempt to include the alignment phenomenon in a mechanical model of cytogel. PMID- 8364422 TI - Cell migration in multicell spheroids: swimming against the tide. AB - Multicell spheroids, small spherical clusters of cancer cells, have become an important in vitro model for studying tumour development given the diffusion limited geometry associated with many solid tumour growths. Spheroids expand until they reach a dormant state where they exhibit a grossly static three layered structure. However, at a cellular level, the spheroid is demonstrably dynamic with constituent cells migrating from the outer well-nourished region of the spheroid toward the necrotic central core. The mechanism that drives the migrating cells in the spheroid is not well understood. In this paper we demonstrate that recent experiments on internationalization can be adequately described by implicating pressure gradients caused by differential cell proliferation and cell death as the primary mechanism. Although chemotaxis plays a role in cell movement, we argue that it acts against the passive movement caused by pressure differences. PMID- 8364423 TI - [Bronchial hyperreactivity after chronic use of salbutamol]. AB - 15 patients with bronchial asthma received inhalations of salbutamol three times daily (200 mcg) for 2 months. Spirometry was carried out at the beginning of the study, one and two months after starting the study. The bronchodilating effect and non-specific bronchial hyperreactivity assessed with the histamine bronchoprovocation test were studied. Two month treatment with salbutamol decreased the bronchodilating effect and at the same time produced an increase of non-specific bronchial hyperreactivity. PMID- 8364424 TI - [Analysis of fenoterol efficacy given as an aerosol using various mouth pieces]. AB - The effect of different mouth pieces on efficacy of fenoterol was studied in 40 patients with atopic and non-atopic bronchial asthma with reversible bronchial constriction. Four devices were studied: standard MDI unit, MDI unit with Boehringer and Astra mouth pieces, MDI unit with spacer. PEF values were registered 7 hours following inhalation. Statistical differences were not significant within the whole group. In selected older patients (above 60 years of age) spacer and Astra mouth pieces produced significant changes. PMID- 8364425 TI - [Therapeutic examination of efficiency for vaccine desensitization with grass pollen catalet]. AB - The results of a 5-year studies on the therapeutical efficiency of Catalet- desensitization vaccine containing grass pollen antigens adsorbed on aluminium hydroxide--are discussed. Catalet vaccine is manufactured by Sera and Vaccines Works in Krakow in the doses of 25 PNU/ml, 250 PNU/ml, 2500 PNU/ml, and 10,000 PNU/ml. It was found that Catalet possesses a strong antigenic properties and enables complete or partial intensivity to grass pollens in the majority of treated patients. Therapeutical efficiency of Catalet has markedly been different than that of placebo, and had expressed fully following a two- or three-year treatment. PMID- 8364427 TI - [Effect of bacteria on chemotaxis of peripheral blood lymphocytes from nonatopic asthmatics]. AB - The chemotactic response of peripheral blood lymphocytes from nonatopic asthmatics and healthy subjects in the gradients of various bacterial strains obtained from the airways of the asthmatic patients was investigated. The dominant autologous strains were found to be effective chemoattractants for lymphocytes form the asthmatics. However, none of the bacterial strains investigated in this study induced increased motility of lymphocytes from healthy subjects. These findings might explain the mechanisms of the accumulation of lymphocytes in the airways of nonatopic asthmatics. PMID- 8364426 TI - [Platelet aggregation and receptor expression of low affinity to IgE (Fc epsilon RII CD23) in patients with seasonal allergic rhinitis]. AB - In 12 patients with pollinosis analysis of platelet function was carried out. Platelet function was assessed basing on the thromboelastogram curve and aggregation capability induced by ADP. Total serum IgE levels, as well as, specific antibodies to grass pollens, IgE and IgG4 levels and circulating receptor of low IgE affinity (sFc epsilon RII/sCD23) were also analysed. The study was carried out in a dynamic state, during natural allergen exposition and natural remission. A significant correlation was found between loss of platelet function and sCD23 levels. The observed relations were not influenced by seasonal changes. PMID- 8364428 TI - [Aerobic and anaerobic bacterial flora as a cause of lower respiratory tract infection]. AB - Bronchial aspirates collected from a group of 100 patients with respiratory infections undergoing broncho-fiberscopic examination have been tested bacteriologically. Twenty five patients was suffered from bronchopneumonia, 35 patients have had acute bronchitis, and 40 patients chronic bronchitis. Aerobic bacterial flora has been detected in 15% of patients, anaerobic flora in 13%, an mixed bacterial flora in 20%, totally in 48% of cases. Aerobic bacteria predominated in pneumonia. Bacteroides melaningogenicus prevailed in anaerobic flora. The tests of bacterial sensitivity to antibiotics have shown high sensitivity to cefotaxime, cefamandole, metronidazole, and rifampicin. PMID- 8364429 TI - Epidemiology of mites allergy of upper respiratory tract and mites occurrence in homes in Warsaw. PMID- 8364430 TI - [Bronchoalveolar lavage (BAL) in patients with pulmonary sarcoidosis. I. Correlations between cellular morphology of BAL with radiologic and respiratory function tests]. AB - BAL, spirometric evaluation and compliance values were analysed in 51 patients (21 females, 30 males; age range 19-51 years). Basing on BAL criteria, 19 had active sarcoidosis, 32 non-active sarcoidosis. Radiological stages (I, II, III) were found in similar percentages in both forms of the disease. Mean respiratory function parameters were similar in the active and non-active stage of the disease. The most common abnormality found in 33% of the patients was decreased DLCO. PMID- 8364431 TI - [Bronchoalveolar lavage (BAL) in pulmonary sarcoidosis. II. Changes in BAL cellular morphology and respiratory function in patients with sarcoidosis treated with prednisone]. AB - BAL and respiratory function were analysed in 26 patients with sarcoidosis (age range 22-48 years) before and after a 12 month steroid therapy trial. 11 patients were in the active stage according to the BAL criteria. After treatment a significant decrease in BAL lymphocytosis was found (a decrease from 31.4% to 22.8%). A significant increase in TLC, DLCOSB and D/VA mean values was found. The effect of steroid therapy was similar in the active and non-active stage of the disease. The authors found BAL useful in monitoring of therapy. PMID- 8364432 TI - [Pulmonary function changes as a late diabetic complications]. AB - During diabetic process angiopathy of lung vessels may be expected. In the study authors evaluated values of spirometric and gasometric parameters in patients with diabetes mellitus in two groups--with and without diabetic complications. It was documented that diabetic process caused the decrease of pulmonary diffusion volume and some gasometric disturbances. This above mentioned spirometric and gasometric changes indicated some coexistence with a late diabetic complications. PMID- 8364434 TI - [Effect of a single dose of nifedipine on pulmonary hypertension measured by doppler echocardiography]. AB - In 14 patients with chronic obstructive pulmonary disease and symptoms of cor pulmonale a single dose of nifedypine was administered and Doppler echocardiography measurements were performed to evaluate a degree of pulmonary hypertension. An acceleration time (AcT) and mean pulmonary artery pressure (MPAP) before and after 20 mg dose of nifedypine were determined, parallel with evaluation of systolic and diastolic blood pressure. In performed examinations it was documented that 20 mg dose of nifedypine induced a decrease of MPAP in observed patients. PMID- 8364433 TI - [Pulmonary thromboembolism--random analysis of autopsy material]. AB - In the study an analysis of 13216 autopsy materials was performed to evaluate a frequency of pulmonary thromboembolism incidence including localisation of detected changes. Pulmonary thromboembolism was determined in 5.5% autopsies, with evident increase in older subjects (up to 31.3% in 70-79 years old group). The most frequently (67.8%) pulmonary thromboembolism was observed in lobar and segmental arteries in a course of atherosclerosis (28.6%), neoplasmas (20.8%) and septic diseases (15.5%). In 25% cases of pulmonary thromboembolism has been diagnosed during clinical observations and has been confirmed by autopsy procedure. PMID- 8364435 TI - [Clinical evaluation of disodium cromoglycate with beta-2-agonist in therapy of patients with atopic bronchial asthma (preliminary study)]. AB - In 38 patients with atopic bronchial asthma DNCG (disodium cromoglycate) and DNCG comp. (disodium cromoglycate and reproterol hydrochloride) were applied in inhalation way. After 7 days course spirometric values were monitoring in all patients. Decrease of Raw values and increases of FEF50 and FEV1 were noticed in all patients, especially in asthmatics treated with DNCG comp. Obtained results suggest a good clinical effect and improvement of spirometric values in patients with atopic bronchial asthma during DNCG and DNCG comp. therapy. PMID- 8364436 TI - [Foreign body of the bronchus in adults]. AB - Two cases of endobronchial foreign bodies are presented. In both an uneventful clinical course following removal of the foreign body and antibacterial therapy was observed. The authors diagnostical problems in cases with scant symptoms, especially presence of non-specific symptoms and uncharacteristic medical history. PMID- 8364437 TI - [Pulmonary lymphangiomyomatosis and tuberous sclerosis--similarities and differences]. AB - Two cases pulmonary lymphangioleiomyomatosis and tuberous sclerosis with pulmonary involvement were presented. Clinical picture of both diseases was similar. Breathlessness was the main symptom of lymphangioleiomyomatosis and there were signs of chylothorax. Chest x-ray interstitial changes disseminated in both lungs. High resolution computer tomography showed numerous cysts in both lungs. Proliferation of smooth muscle bundles was found in lung biopsy. Main symptoms of tuberous sclerosis were breathlessness on exertion and recurrent pneumothorax. Changes in chest x-ray, CT and lung biopsy were similar to found in lymphangioleiomyomatosis. Diagnosis of tuberous sclerosis was based on typical extrapulmonary signs and symptoms. PMID- 8364438 TI - [Extracorporeal membrane oxygenation]. PMID- 8364439 TI - [Psychogenic disturbances of laryngeal function]. PMID- 8364440 TI - [Who first described the Heimlich maneuver in Poland?]. PMID- 8364441 TI - National advisory committee on immunization (NACI). Statement on hepatitis B vaccine. AB - The following recommendations on hepatitis B vaccine from NACI will appear in the 4th edition of the Canadian Immunization Guide scheduled for publication in autumn 1993. They contain updated information on the epidemiology of hepatitis B in Canada and response to hepatitis B vaccine. In addition to vaccinating targeted high-risk populations, routine childhood immunization is now recommended although details on the preferred target age group and schedule are not yet finalized. There are some changes to the sections on pre-exposure immunization, post-exposure management, routine boosters (no longer needed), and post vaccination serology. Finally, the statement incorporates the new vaccine dosages for infants and children for Merck Sharp and Dohme's Recombivax HB, approved January 1992, and SmithKline Beecham's Engerix-B, approved September 1992. PMID- 8364442 TI - Fluorometric determination of L-tryptophan with methoxyacetaldehyde. AB - It was observed in our laboratory that methoxyacetaldehyde induced strong fluorescence with L-tryptophan in the presence of NaNO2 at pH 2.75. The reaction mixture was heated at 80 degrees C for 15 min and the fluorescence was measured at the excitation wavelength, 253 nm and the emission, 450 nm. Amino acids other than L-tryptophan did not produce fluorescence under the conditions employed. A good linear working curve was observed between 25 pmol/50 microliters and 500 pmol/50 microliters of L-tryptophan. The limit of determination for L-tryptophan was 10 pmol/50 microliters. The coefficient of variation of the measurements (n = 5) was 1.5% for 250 pmol/50 microliters of L-tryptophan. The proposed method was successfully applied to the analyses of tryptophan in a pooled human serum. Total tryptophan was determined after deproteinization with trichloroacetic acid, and free tryptophan was determined using the ultrafiltrate of a pooled human serum. Analytical recoveries of total and free tryptophan were 98.8% and 99.1%, respectively. The fluorescent products of L-tryptophan and methoxyacetaldehyde were characterized as beta-carboline and 1-methoxymethyl-beta-carboline by the use of liquid chromatography-mass spectrometry (LC-MS) and HPLC. PMID- 8364443 TI - Alteration in reactivity of sphingomyelinase from Streptomyces sp. modified with a polyethylene glycol derivative. AB - Purified sphingomyelinase of Streptomyces A9107 (NRRL 15100) was modified with ss PEG, methoxypolyethyleneglycol succinimidyl succinate, without loss of activity toward sphingomyelin in the mixed micelles with detergents such as sodium deoxycholate and Triton X-100 or toward a water-soluble, synthetic substrate, HNP, 2-(N-hexadecanoylamino)-4-nitrophenyl phosphocholine. The hemolytic and sphingomyelin-hydrolyzing activities of the enzyme toward intact bovine erythrocyte membrane were completely abolished by modification with ss-PEG, whereas the activity toward membranous sphingomyelin in the erythrocyte ghosts was fully retained. The enzyme activity toward liposomal sphingomyelin (large and small unilamellar vesicles) was significantly decreased by PEG-modification. The thermostability of sphingomyelinase was greatly increased by modification with ss PEG, whereas the sensitivity of the enzyme to proteolysis was not influenced by that modification. PMID- 8364444 TI - Reduction of nitro and azo compounds by NADPH-cytochrome P-450 reductase cytochrome c heme peptide system. AB - Octa heme peptide, an enzymic digestion product of Candida Krusei cytochrome c, was found to catalyze nitro and azo reduction in the presence of NADPH and NADPH cytochrome P-450 reductase under anerobic conditions. The reduction was dependent on the concentrations of heme peptide and reductase, and inhibited by carbon monoxide and oxygen. Comparison of the activities of the reductase-heme peptide system with liver microsomes revealed that heme peptide was as effective as cytochrome P-450 in nitro reduction, although less effective in azo reduction. Thus, cytochrome c heme peptide may serve as an artificial substitute for cytochrome P-450 at least in the reductive metabolism of xenobiotics. PMID- 8364445 TI - Effect of a monoclonal anti-sperm antibody (A-1) on in vitro fertilization in the mouse. AB - We prepared four monoclonal antibodies raised against mouse spermatozoa. The ability of the hybridoma culture supernatants to inhibit in vitro mouse fertilization was determined. One of these monoclonal antibodies, termed A-1, strongly inhibits sperm penetration into zona pellucida of egg in a concentration dependent fashion. On the other hand, even in the presence of the same concentration of A-1 antibody, sperm binding to comulus-free eggs was slightly inhibited and sperm-egg fusion was not inhibited at all. Immuno-fluorescence studies with A-1 showed that it recognizes an antigen(s) localized in the acrosome of mouse spermatozoa. In the case of unfixed sperm, the acrosome-intact sperm (i.e., sperm bound to egg zona pellucida) and unbound sperm were slightly immunostained with A-1 antibody (1.6% and 9.0%, respectively). All the full acrosome reacted sperm (i.e., sperm penetrating into the perivitelline space) were not immunoreacted. On the other hand, when sperm were fixed with methanol, approximately 80% of unbound sperm were immunoreacted with this antibody. Furthermore, almost all of zona-binding sperm were immunostained, whereas acrosome reacted, penetrating sperm were not. These data suggested that the antigen recognized by A-1 was located inside the plasma membrane of spermatozoa, and appeared on the surface of the spermatozoa during the period of penetration into egg zona pellucida. After sperm penetration into the perivitelline space this antigen must be released from the sperm. PMID- 8364446 TI - Effect of cupric ion on cholesteryl ester hydrolysis in rat peritoneal macrophages. AB - The inhibitory effects of Cu2+ on the hydrolysis of cholesteryl [4-14C]oleate droplets in rat peritoneal macrophages were studied. Macrophages rapidly incorporated cholesteryl [4-14C]oleate droplets and hydrolyzed at a linear rate over 9 h. When macrophages were preincubated in the medium containing Cu2+, the hydrolysis of cholesteryl oleate within macrophages was markedly inhibited by Cu2+ and eventually led to the accumulation of cholesteryl oleate in macrophages. The inhibitory effect on the hydrolysis of cholesteryl oleate was dependent on the concentration of Cu2+. Also, the activity of acid cholesteryl ester hydrolase (acid CEH) in lysosomal fractions isolated from rat peritoneal macrophages with Cu2+ showed a marked decrease. This decrease also occurred in a dose dependent manner. These results suggest that Cu2+ inhibits the hydrolysis of cholesteryl ester in macrophages, and that the accumulation of cholesteryl ester in macrophages of the early atheroscleotic lesion is responsible for the decrease of lysosomal acid CEH activity. PMID- 8364447 TI - Effect of histamine on memory retrieval in old rats. AB - Effects of intracerebroventricular (i.c.v) injection of histamine (Hi) and its related compounds on prolongation of the response latency ensuing after a long interruption of learning were studied by testing the active avoidance response in old rats. After Hi application at doses of 50 and 100 ng, the response latency became significantly shorter than that determined in the pre-injection periods, suggesting that Hi facilitates memory retrieval in old rats. H1-agonists, 2 methylHi and 2-thiazolylethylamine, effected a dose-related shortening of response latency as seen after Hi application, whereas H2-agonists, 4-methylHi and impromidine, failed to prompt the response latency. Simultaneous i.c.v. injection of pyrilamine, a H1-antagonist and Hi abolished the Hi-induced shortening of response latency. Furthermore, intraperitoneal administration of histidine at doses of 200 and 500 mg/kg significantly shortened the response latency. Neither (R)-alpha-methylHi nor thioperamide caused a significant effect indicating that H3-receptor may not be involved in Hi-induced facilitation of memory retrieval. Based on these findings, it may be concluded that Hi takes an active part in facilitating memory recall via H1-receptor in old rats. PMID- 8364448 TI - Effect of bredinin on early embryonic development in mice. AB - Bredinin, an immunosuppressive agent, had a teratogenic effect and a decreasing effect in litter size in mice and in rats. We investigated the direct effect of bredinin on the development of mouse preimplantation embryos in vitro. Bredinin strongly inhibited the first differentiation step from the morula to the blastocyst stage, whereas the steps from the two-cell embryo to the morula stage were not inhibited. At 10(-6) or 10(-5) M of bredinin, only one or none of the morula embryos developed to a blastocyst after a 48 h culture; while approximately 90% of the embryos developed to blastocysts in the absence of bredinin. To determine whether the bredinin inhibition was reversible, the morula embryos were cultured with 10(-5) M of bredinin for 48 h. The embryos were transferred to bredinin-free culture conditions, and their development was observed. The inhibitory effect of bredinin was reversible. The expansion of zona free blastocyst was also inhibited by bredinin. When blastocyst embryos were cultured in the presence of bredinin (10(-6) M), the mean size of the embryos was reduced to half the initial size. In addition, the steps of hatching from the zona pellucida and attaching to the substratum were significantly inhibited by bredinin. Trophoblast outgrowth was completely inhibited by 10(-6) M bredinin; however, the area of trophoblast outgrowth was expanded to 18-fold the initial size after a 96 h culture in the absence of bredinin. Thus, the decrease in the number of offspring is due to the direct effect of bredinin on mice embryos. PMID- 8364449 TI - Formation of a new 1,1,1 adduct in the reaction of malondialdehyde, n-hexylamine and alkanal under neutral conditions. AB - The reactions of malondialdehyde (MDA) with n-hexylamine (HA) in the presence of alkanals at a neutral pH were investigated. Two new compounds, 1,1,1 adduct (4a) and fluorescent compound (3a), were isolated from the reaction of MDA, HA and acetaldehyde. Compounds 4a and 3a were identified as 2-formyl-3-hexylamino-3 methylpropanal and 1-hexyl-5-hexyliminomethylene-4-methyl-1,4-dihydropyridine-3 carba ldehyde, respectively. Similar compounds (4b and 3b) were obtained from the reaction of MDA, HA and propanal. Compound 4 was obtained in a high yield. In addition, the reactivity of MDA towards phenylethylamine (PEA) in the presence or absence of alkanals was investigated. The results indicated that MDA was of low reactivity in the absence of alkanals at neutral pH. However, when alkanals coexisted, MDA showed high reactivity towards PEA. PMID- 8364450 TI - Difference in rectal absorption of morphine from hollow-type and conventional suppositories in rabbits. AB - The bioavailability of morphine after rectal administration using three types of suppositories containing morphine hydrochloride (10 mg) in different added forms was evaluated in rabbits. Three types of suppositories were constructed with a base material (Witepsol H-15): a conventional suppository containing morphine hydrochloride mixed with a base material, a hollow-type suppository containing morphine in an aqueous solution in its cavity, and a hollow-type suppository containing morphine as a powder (hydrochloride salt) in its cavity. The plasma concentrations of morphine and its metabolites, morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G), were determined. The mean AUC0-6 of morphine after rectal administration of the hollow-type suppository containing powdered morphine was significantly higher than that after the administration of a conventional suppository, whereas the mean AUC0-6 of M-3-G was lower than that after administration of a conventional suppository. The mean AUC0-6 of M-6-G by a hollow-type suppository containing powdered morphine was higher than that by a conventional suppository. Although the mean AUC0-6 ratio of M-3-G to morphine after administration of a conventional suppository was three times larger than that of a hollow-type suppository containing powdered morphine, the mean AUC0-6 ratios of M-6-G to morphine after use of the three types of suppositories were all approximately 1.0. This study demonstrates that the hollow-type suppository containing powdered morphine is a more effective rectal dosage vehicle than the conventional suppository. PMID- 8364451 TI - Transport of aspirin and its metabolites through human erythrocyte membrane. AB - The transport of aspirin (ASP) and its metabolites (salicylic acid (SA), salicyluric acid (SAU), gentisic acid (GA) and gentisuric acid (GAU)) through human erythrocyte membrane was investigated. ASP permeated rapidly into the erythrocytes and the concentration dwindled gradually after the maximum concentration was attained almost within one minute. It was suggested that SA is released from the erythrocytes after ASP transported into the erythrocytes is hydrolyzed in them. In both an inward and outward direction, the transport rates of SA and GA were rapid, while those of SAU and GAU were lower by conjugating glycine. It was suggested that GAU remains for a long time in a living body. The rate of transport of GA and GAU were markedly obstructed by the band 3 protein inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate, although the transport rates of SA and SAU were obstructed only slightly. It was suggested that the transport of GA and GAU are mediated through band 3 protein. PMID- 8364452 TI - Effect of mexiletine on elimination and metabolic conversion of theophylline and its major metabolites in rats. AB - In an attempt to clarify the possible mechanism of the interaction between theophylline (TP) and mexiletine (ME), the elimination kinetics and in vitro metabolism of TP and its metabolites were investigated in rats. The plasma elimination of TP, 1,3-dimethyluric acid (1,3-DMU) and 1-methyluric acid (1-MU) was significantly delayed by the intravenous (i.v.) administration of ME. The oral administration of ME also decreased the elimination rate of TP to the same extent as the i.v. dosing. The in vitro metabolic experiment showed that ME significantly inhibited the metabolic conversion of TP to 1,3-DMU and, 1,3-DMU to 1-MU, and slightly inhibited the conversion of TP to 3-methylxanthine, these processes being mediated by microsomal enzymes, with no inhibition of xanthine oxidase. Our results indicated that ME could inhibit the metabolic conversion of TP and its metabolite in rat, as reported in man. PMID- 8364454 TI - Controlled release of insulin from plasma-irradiated sandwitch device using poly DL-lactic acid. AB - The release behavior of insulin from a plasma-irradiated sandwitch (PIS) device using poly-DL-lactic acid (PLA) was studied. The controlled release device can be obtained by oxygen plasma irradiation (radiofrequency discharge operating at 13.56 MHz) on the outer layer of the sandwitch device which was fabricated from an insulin-PLA matrix tablet as a core material and a mixture of plasma degradable polyoxymethylene (POM) and biodegradable PLA as a wall material. The release test indicated that insulin was released through the micropores formed by the vaporization of POM, and that the release behavior of insulin was affected largely by the molecular weight of PLA used as the outer layer rather than the plasma operational condition. The release of insulin can be controlled by the use of PLA with an average molecular weight of 11000 as the outer layer of the PIS device. Insulin from the PIS device maintained normal blood glucose levels for 10 d in diabetic rats as an implantable dosage form. The duration of insulin effectiveness was relatively short considering the degradation rate of PLA, indicating that the degradation characteristics of biodegradable PLA were not well reflected in the PIS device. PMID- 8364453 TI - Enhancement effect of an ethanol/Panasate 800 binary vehicle on anti-inflammatory drug permeation across excised hairless mouse skin. AB - The novel binary vehicle system consisting of ethanol (EtOH) and Panasate 800 as tricaprylin was applied to five types of nonsteroidal anti-inflammatory drugs, and its enhancing effect on drug permeation across hairless mouse skin in vitro was assessed. The permeability of all drugs was remarkably increased by the treatment of skin with EtOH/Panasate 800 binary systems compared with either EtOH or Panasate 800 alone, and the effect reached a maximum in EtOH/Panasate 800 (40/60) system. With regard to this binary system, the skin permeation ratio or flux of the drug increased in the following order: salicyluric acid (SU) > salicylic acid (SA) > alclofenac (ALC) > ketoprofen (KP) > ibuprofen (IBU). The one-layer skin model was applied concerning the above skin permeation profiles of the five drugs. Diffusion parameter (D'), partition parameter (K'), and permeation constant (Kp = D' x K') were calculated using the Laplace-transformed equations with the aid of MULTI (FILT). It was well demonstrated that the reduction of lag time and the increase of flux caused by EtOH/Panasate 800 binary vehicle systems was due to an increase of D' value by Panasate 800 and K' value by EtOH, respectively, in the skin. Especially, the EtOH/Panasate 800 (40/60) binary vehicle system produced the largest Kp value in each drug. In relation to all the EtOH/Panasate 800 binary vehicle systems, the logarithms of calculated Kp were found to be in inverse proportion to the logarithms of a n-octanol/water partition coefficient (P) of the drug which appeared in previous literature. PMID- 8364456 TI - Low mitogenic activity of synthetic lipid A analog, 2,3-acyloxyacylgalactosamine 4-phosphate, in cultured murine splenocytes. AB - The mitogenicity of chemically synthesized lipid A analogs, 2,3 acyloxyacylglucosamine-4-phosphate (A-103) and 2,3-acyloxyacylgalactosamine-4 phosphate (A-113), was compared. Synthetic lipid A analogs of the disaccharide type (506), the monosaccharide-type (A-103) suspended in RPMI-1640 medium supplemented with triethylamine, and Salmonella typhimurium LT-2 lipopolysaccharide (LPS) were capable of increasing the incorporation of [3H]thymidine into splenocytes of C57BL/6 mice at various doses ranging from 1.0 to 100 micrograms/ml. However, the mitogenic activity of A-113 at these doses was markedly weaker than the activity of the above materials. When the A-103 and A 113 were suspended in RPMI-1640 medium supplemented with ethanol, the mitogenic activity of A-113 also showed lower activity than that of A-103 in the splenocytes of C57BL/6 mice. These findings indicate that the mitogenic activity of synthetic lipid A of the monosaccharide-type is affected by a kind of composed sugar. PMID- 8364455 TI - A novel colorimetric method for determination of glycated protein based on 2-keto glucose release with hydrazine. AB - We tried to measure glycated proteins by a novel method based on colorimetry of 2 keto-glucose which is released from the glycated protein (ketoamine) on heating with hydrazine. Reaction conditions were optimized with glycated human serum albumin (glc HSA) as a model compound. Ketoamine reacted quantitatively with hydrazine on heating at 100 degrees C for 0.5 h, followed by heating with phenylhydrazine at 60 degrees C for 1 h. Glucose interference with the assay was eliminated by preincubation of the sample with glucose oxidase at 37 degrees C for 0.5 h. Time courses for the coloration of glc HSA and human serum showed a profile similar to that of N-p-tolyl-D-isoglucosamine under optimized reaction conditions. The lower limit for the assay of glc HSA was 0.7 microM. The serum level of glycated proteins measured by the present method correlated well with that (fructoamine value, microM) measured by the conventional method (nitroblue tetrazolium-reducing method) (r = 0.92, n = 35). In conclusion, the present method is a novel, highly sensitive and reliable one for measuring glycated proteins in biological samples. PMID- 8364458 TI - S-methyl methane thiosulfonate, a new antimutagenic compound isolated from Brassica oleracea L. var. botrytis. AB - Though various antimutagens with desmutagenic activities have been found in our daily foods of plant origin, the numbers of antimutagens with bio-antimutagenic activities found so far are limited. In the present study, a compound with potential bio-antimutagenic activity to Escherichia coli B/r WP2 was newly isolated from cauliflower, Brassica oleracea L. var. botrytis, and its chemical structure was identified to be S-methyl methane thiosulfonate by NMR and MS analysis. PMID- 8364457 TI - Effects of dimethylpyrazine isomers on reproductive and accessory reproductive organs in male rats. AB - The effects of dimethylpyrazine isomers on reproductive and accessory reproductive organs in male rats were studied. Following the administration of 2,5-dimethylpyrazine (100 mg/kg, s.c.) the weight of prostate and seminal vesicles, as well as testosterone levels in plasma were significantly decreased. One isomer of dimethylpyrazine, 2,6-dimethylpyrazine (100 mg/kg, s.c.), affected only the seminal vesicles, while 2,3-dimethylpyrazine had no influence on accessory reproductive organs. Following administration of 100 mg/kg of 2,5 dimethylpyrazine, acid phosphatase activity in the prostate and fructose content in the seminal vesicles were also significantly decreased compared with tissues from vehicle-treated animals. Weight of the testes and acid phosphatase activity therein were not affected following the administration of 2,5-dimethylpyrazine, nor were numbers of spermatozoa in the epididymis. These results showed that 2,5 dimethylpyrazine induced decrease in prostate and seminal vesicle weight by inhibiting testosterone uptake and reducing plasma testosterone levels. PMID- 8364460 TI - Specific inhibitory effect of hybrid liposomes on growth of human lymphoma-human lymphocyte B hybridoma cells in vitro. PMID- 8364459 TI - Isolation of bilobalide and ginkgolide A from Ginkgo biloba L. shorten the sleeping time induced in mice by anesthetics. AB - The leaves of Ginkgo biloba L. and aqueous extract from them shortened the sleeping time induced in mice by anesthetics (hexobarbital, alpha-chloralose and urethane, i.p.). Two characteristic terpenoids in G. biloba, bilobalide and ginkgolide A, significantly shortened the sleeping time induced by anesthetics. A toxic substance, 4-O-methylpyridoxine (MPN), responsible for "gin-nan food poisoning" isolated from the seed of G. biloba, was not detected from the extract of the leaves of G. biloba. Therefore, the Ginkgo biloba extract has no toxicities for MPN. PMID- 8364461 TI - Preparation of fluorescence labeled insulins, sulfobenzoxadiazolyl-insulins, for fluorescence immunoassay. AB - The preparation of insulins labeled with a fluorescent moiety at a definite position (Gly(A1) or Lys(B29)) on the molecule is described. Gly(A1)- and Lys(B29)-S-acetylthioglycoloyl-insulins and Gly(A1)-2(or 3)-acetylmercapto-3 carboxypropranoyl-insulin were deacetylated and then reacted with 7-chloro-4 sulfobenzoxadiazole, a fluorogenic reagent, to afford the corresponding fluorescence labeled insulins. The preparative separation of the fluorescence labeled insulins from the insulin derivatives that remained unreacted was carried out by anion-exchange high-performance liquid chromatography on a TSKgel DEAE-2SW column. PMID- 8364462 TI - Evidence of conversion of estradiol 17-sulfate to its 2- and 4-hydroxylated catechols by human placental microsomes. AB - When estradiol 17-sulfate (ES) was incubated with human placental microsomes under an NADPH-generating system, 2- and 4-hydroxyestradiol 17-sulfates (2- and 4 OH-ES) formed as the main products. By kinetic experiments, the apparent Km values of 44.0 and 360 microM and apparent Vmax values of 236 and 140 pmol/mg protein/10 min were obtained for the 2- and 4-hydroxylation, respectively. The results indicate that human placental microsomes have fairly high 2- and 4 hydroxylase activities toward ES. This paper describes the formation of 2- and 4 OH-ES and speculates on their physiological role during pregnancy. PMID- 8364463 TI - Preparation and evaluation of fatty acid esters of 2-(4-hydroxyphenyl)-4,5 diphenylimidazole as fluorescent substrates for measurement of lipase activity. AB - A series of four aliphatic carboxylic acid esters (acetate, caproate, laurate and palmitate) of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole (HDPI) was prepared. Usefulness of these esters as fluorescent substrates for the measurement of lipase activity was evaluated using a high performance liquid chromatographic method. The hydrolysate, HDPI, could be well separated from each substrate by a reversed-phase column and detected at 440 nm emission (cutoff-filter) with 360 nm excitation. Lipase from Candida cylindracea was used for the investigation. From their kinetic parameters, the caproate and laurate were found to be suitable for the lipase. Using the laurate, from 5 to 500 mU per assay tube of the lipase was determined. PMID- 8364464 TI - Serum components induce beta-D-glucan-inhibitable uptake of zymosan particles by murine peritoneal macrophages. AB - Effects of murine serum (NMS) treatment on (1-->3)-beta-D-glucan inhibitable uptake of zymosan particles (ZYM) (GIZUP) by murine peritoneal macrophages (PM) and the structural specificity of the inhibition were examined. ZYM uptake by PM treated with NMS was enhanced in comparison with those treated with medium, and in a concentration- and incubation time-dependent manner. The enhanced ZYM uptake was significantly reduced by the pretreatment of PM with soluble (1-->3)-beta-D glucans. These facts suggest that NMS enhances GIZUP. The effect disappeared by the treatment of NMS with gelatin-Sepharose which removed fibronectin (FN) from the serum, suggesting a significant contribution of FN on GIZUP. In addition, the administration of beta-glucan in vivo elevated the concentration of FN in serum by acute phase response and enhanced GIZUP, suggesting the positive contribution of acute phase responses on beta-glucan mediated immunopharmacological activities. Of particular interest, the inhibition was shown by both antitumor active and inactive glucans. These facts suggested that the recognition of beta glucans by PM, which would proceed at a relatively early period of whole activation pathways, would not be enough to fully activate the host to show antitumor activity. PMID- 8364465 TI - Metabolism of mutagenicity-deprived 3-fluoroquinoline: comparison with mutagenic quinoline. AB - 3-Fluorinated quinoline (3FQ), a non-mutagenic derivative of the potent mutagen quinoline, was metabolized with a microsomal enzyme fraction isolated from the 3 methylcholanthrene-treated rat liver. The metabolites were 3-fluoro-5,6 dihydroquinoline-5,6-trans-diol (72%), 3-fluoroquinoline 1-oxide (6%), 3-fluoro 5,6-dihydroquinoline-5,6-cis-epoxide (1%), and 4 unidentified metabolites (11%). Since this metabolic pattern is similar to that obtained with unfluorinated quinoline, the epoxidation of the benzene moieties of quinoline and 3 fluoroquinoline is most likely a detoxication process and not mutagenic activation. PMID- 8364466 TI - Arabinogalactan core structure and immunological activities of ukonan C, an acidic polysaccharide from the rhizome of Curcuma longa. AB - Controlled Smith degradation of ukonan C, a phagocytosis-activating polysaccharide isolated from the rhizome of Curcuma longa L., was performed. The reticuloendothelial system-potentiating, anti-complementary and alkaline phosphatase-inducing activities of ukonan C and its degradation products were investigated. Methylation analyses of the primary and secondary Smith degradation products and of a de-arabinosylated product indicated that structural features of the arabinogalactan core of ukonan C include a backbone chain composed of beta 1,3-linked D-galactose and beta-1,4-linked D-xylose. All of the galactose units in the backbone carry side chains composed of beta-1,6-linked D-galactosyl residues with or without terminal alpha-L-arabinose units at position 3. Ukonan C showed remarkable effects on both reticuloendothelial system-potentiating and alkaline phosphatase-inducing activities. Periodate oxidation caused a decrease in or disappearance of the immunological activities, but the controlled Smith degradation product having the arabinogalactan core structure of polysaccharide showed a pronounced effect on anti-complementary activity. PMID- 8364467 TI - Three rhamnose-binding lectins from Osmerus eperlanus mordax (olive rainbow smelt) roe. AB - Three rhamnose-binding lectins were purified from the roe of Osmerus eperlanus mordax (olive rainbow smelt) by affinity chromatography and ion-exchange chromatography. The apparent molecular weights of Osmerus eperlanus mordax lectin (OML) -1, -2 and -3 were 25000, 32000 and 26000, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. On native PAGE, these three lectins showed different migration patterns (Rm value; 0.37, 0.53 and 0.66, respectively). OMLs agglutinated rabbit and human type B erythrocytes and sarcoma 180 cells, but not human type A and O erythrocytes and AH109A cells. The most effective monosaccharide inhibitor was L rhamnose. L-Mannose and D-galactose were also good inhibitors. Furthermore, OML induced hemagglutination was inhibited more strongly by melibiose or raffinose rather than lactose or lactulose. Therefore, OMLs are L-rhamnose/alpha-D galactosyl type lectins. OMLs did not require a detergent, when extracted from crude material, and Ca2+, Mg2+, EDTA and dithiothreitol were not necessary for the OML-induced hemagglutination activities. The OMLs had similar N-terminal amino acid sequences. PMID- 8364468 TI - Neurotropic pyrimidine heterocyclic compounds. I. The newly synthesized pyrimidine compounds promote neurite outgrowth of GOTO and neuro 2a neuroblastoma cell lines, and potentiate nerve growth factor (NGF)-induced neurite sprouting of PC 12 cells. AB - From the study using cultured human and mouse neuroblastoma cells, we found that a new type of synthetic bicyclic pyrimidine compounds possessing piperazine moiety strongly promoted neurite outgrowth in neuroblastoma cell lines human GOTO and mouse neuro 2a. The most effective compounds of these 2-piperazinopyrimidine derivatives possessing nerve growth factor (NGF)-like activity were 2-piperazino 6-oxo-5,6-dihydro(7H)pyrrolo[2,3-d]pyrimidine and 2-piperadino-6-methyl-5-oxo-5,6 dihydro(7H)pyrrolo[3,4-d]pyrimidin e. The piperazinopyrimidine compounds were also shown to potentiate NGF-induced neurite sprouting of rat pheochromocytoma PC12 cells. The compounds were more effective in cell cultures than isopropylaminopyrimidine (isaxonine) which had been previously developed and then withdrawn. We discussed the merit of the method of the screening of neurotropic compounds by neurite sprouting activity in cultured neuroblastoma cells. PMID- 8364469 TI - Feasibility of use of several cardiovascular agents in transdermal therapeutic systems with l-menthol-ethanol system on hairless rat and human skin. AB - Effect of the simultaneous use of l-menthol and ethanol on the skin permeation of six potent cardiovascular agents: nicardipine hydrochloride, atenolol, captopril, nifedipine, vinpocetine and nilvadipine (in hydrophilic order) was investigated to evaluate the feasibility of their use in a transdermal therapeutic system (TTS). In vitro diffusion experiments were carried out using excised hairless rat and human skin, and the application area of TTS required for the minimum therapeutic effect was estimated by a simple pharmacokinetic calculation. Marked enhancing effect by the l-menthol-ethanol system was found independent of drug lipophilicity, but the mode of action was dependent on the lipophilicity of the drug. The action of the system on lipophilic drugs (nifedipine, vinpocetine and nilvadipine) was mainly due to their increase in solubility in the system, while that on hydrophilic (or water soluble) drugs (nicardipine hydrochloride, atenolol and captopril) was the result of increase in their skin permeability coefficient. This enhancing effect was adequate to assure their minimum effective concentration (MEC) in human. The area of application of a drug to maintain the MEC was calculated to be 0.15 cm2 for hydrophilic or water soluble drugs and 3.7 13 cm2 for lipophilic drugs. PMID- 8364471 TI - In vivo release of water-soluble drugs from stabilized water-in-oil-in-water (W/O/W) type multiple emulsions following intravenous administrations using rats. AB - The in vivo release of four water-soluble drugs, cefadroxil, cephradine, antipyrine and 4-aminoantipyrine, from a stabilizing water-in-oil-in-water (W/O/W) type multiple emulsion was studied using rats. The W/O/W type multiple emulsion used in this study could be stabilized for 30 d after preparation at room temperature and also for 24 h in pH 7.4 isotonic phosphate buffer or in rat plasma at 37 degrees C. The cefadroxil and cephradine concentrations in rat plasma following intravenous administrations of their W/O/W type multiple emulsions containing drugs were considerably prolonged compared with those of respective aqueous solutions. Sustained-releasing properties of cefadroxil and cephradine from W/O/W type multiple emulsions could be explained by the mechanism underlying the long residence time of W/O/W type multiple emulsions and delay release of drugs from the W/O/W type multiple emulsions circulated with rat blood stream. However, antipyrine and 4-aminoantipyrine decreased rapidly following W/O/W type multiple emulsions and these plasma profiles coincided precisely with those following intravenous administration of the aqueous solutions of drugs. These in vivo releasing data correlated with in vitro drug release observation stated in the previous papers. PMID- 8364470 TI - Enhanced absorption of bumetanide from suppositories containing weak acids in rabbits. AB - The in vitro release of bumetanide from macrogol suppositories with and without weak acids (citric acid and tartaric acid) was studied. The release of bumetanide was not affected when weak acids were added to the suppositories. The in vivo rectal absorption of bumetanide from the suppositories was evaluated in rabbits. The bioavailability (absolute), expressed as the ratio of the area under the plasma concentration-time curve (AUC) following oral administration of bumetanide, was 39% that of intravenous administration. The value in bumetanide following rectal administration of the suppositories without weak acids was 32%. Each absolute bioavailability following rectal administration of the suppositories with 5% citric acid and 5% tartaric acid was 52% and 42%, respectively. These values were significantly larger than those of rectal administration of the suppositories without weak acids. Particularly, the bioavailability following rectal administration of the suppositories containing citric acid was significantly different from even those of oral administration. The absorption rate constants of bumetanide from the suppositories with weak acids were significantly larger than those following oral administration. These results indicated the possibilities of the rectal route of administration of drugs which are weak organic acids and show low or variable bioavailability following oral administration. PMID- 8364472 TI - Construction of a physiologically based pharmacokinetic model to describe the hepatobiliary excretion process of ligands: quantitative estimation of intracellular diffusion. AB - A physiologically based pharmacokinetic model was established to describe the hepatobiliary excretion process for ligands which are excreted into the bile without metabolic conversion. In this model, the following processes were taken into consideration: influx and efflux across the liver sinusoidal membrane, intracellular diffusion, and excretion across the canalicular membrane into the bile. The partial differential equation by which these processes were described was solved to obtain the Laplace transformed solution for the biliary excretion rate of ligands, based on the plasma concentration profiles as an input function. The time profiles for the biliary excretion rate of dibromosulfophthalein (DBSP; 6.80 mg/kg b.w.) or cefodizime (15.0 mg/kg b.w.) after i.v. bolus administration to rats were fitted to the solution using a nonlinear least-squares program based on a fast inverse Laplace transform (MULTI-FILT [Y. Yano et al., Chem. Pharm. Bull., 37, 1035 (1989)] to determine the permeability-surface area product across the plasma membrane as well as the apparent intracellular diffusion coefficient. DBSP and cefodizime were used as model compounds since these two ligands possess different binding characteristics for cytosol protein(s). Although both ligands are present predominantly in the cytosol, DBSP binds to intracellular protein(s) (such as ligandin) to a great extent whereas the protein binding of cefodizime is not so extensive. The fitted lines were superimposed on the experimental results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364473 TI - Sensitive determination of ambenonium in plasma using inhibitory activity to acetylcholinesterase. AB - A sensitive analytical method for the determination of ambenonium, a selective acetylcholinesterase inhibitor, in plasma was developed. The procedure involves ultrafiltration to remove endogenous plasma cholinesterase, followed by colorimetric measurement of the inhibitory activity to acetylcholinesterase by the thiocholine method. Coefficient of variation of within-day triplicate analysis is less than 20% at the concentration of 5 nM. Detection limit of this method is 1 nM, which is twice lower than the most sensitive HPLC method reported previously. This assay procedure is applied to the pharmacokinetic study of ambenonium after intravenous administration of low dose (10-20 nmol/kg) to rat. This new method is rapid and simple and makes it possible to determine the ambenonium concentration in plasma with good accuracy. PMID- 8364474 TI - Binding of lysozyme to synthetic monosaccharide lipid A analogue, GLA60. AB - Recent studies by our group suggested that lysozyme (LZM) has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A, well-known as sharing large part of lipid A activities but with very low toxicity. In this study, we characterized the interaction of LZM with GLA60 in comparison to that with E. coli 0111 LPS (smooth form), taking a physicochemical approach. Using a dansylated lysozyme probe (DNS-LZM), LZM was found to bind to GLA60 in all 3 of its forms, free acid, triethylamine (TEA) salt and bovine serum albumin (BSA) complex of GLA60, as well as natural LPS. Compared with LPS, the complex formation of the TEA salt was weakly dependent on temperature and incubation time. LZM also bound to biologically inactive GLA analogues, GLA 64 and GLA69, at a high affinity, as well as to GLA 60. By using chemically modified LZM, it was found that the ionic as well as hydrophobic interactions are important for the complex formation. PMID- 8364475 TI - Uptake of glycyrrhizin by isolated rat hepatocytes. AB - The mechanism of uptake of glycyrrhizin (GLZ) by isolated rat liver cells was studied. The uptake rate was dependent on the unbound GLZ concentration. The initial uptake rate with respect to the unbound GLZ concentration reflected the operation of both saturable and nonsaturable processes, which followed Michaelis Menten type kinetics; the process involves a Km of 11.3 microM, Vmax of 0.112 nmol/min/10(6) cells, and a first-order rate constant (Kd) of 0.195 nmol/min/10(6) cells/mM. GLZ adsorption on the cell membrane occurs at two types of binding sites with a linear adsorption coefficient = 2.81 nmol/10(6) cells/mM and a dissociation constant = 18.3 microM and its adsorption capacity = 0.12 nmol/10(6) cells describing specific adsorption. GLZ uptake did not require the presence of Na+ in the incubation medium and was not significantly inhibited by ouabain. The Arrhenius plot of uptake of 10 microM GLZ presented a single straight line in the range of 4-37 degrees C, with an activation energy of 15.9 kcal/mol. An energy requirement was also demonstrated, as all metabolic inhibitors studied (rotenone, antimycin A, 2,4-dinitrophenol, and KCN) significantly reduced the uptake of 10 microM GLZ (p < 0.01). The uptake was competitively inhibited by glycyrrhetinic acid (GLA), taurocholate (TCA), and probenecid (PBC) with inhibition constants, Ki, of 13.7, 48.5, and 115.9 microM, respectively, and it was noncompetitively inhibited by bromosulfophthalein (Ki 9.2 microM) and indocyanine green (Ki 13.5 microM) only at low GLZ concentrations (5 and 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364477 TI - Fluorometric assay of rat brain N-methyltransferase with 4-methylnicotinamide. AB - A fluorometric method for the assay of rat brain N-methyltransferase (NMT) has been developed using rat brain 9000 x g supernatant fluid as an enzyme preparation. The method is based on the enzyme reaction at pH 8.6 using 4 methylnicotinamide (4-MN) as the methyl acceptor substrate in the presence of cofactor S-adenosyl-L-methionine (AdoMet), and the fluorometric determination of the product 1,4-dimethylnicotinamide by means of its reaction with 4 methoxybenzaldehyde. The apparent Km values for 4-MN and AdoMet were 0.47 mM and 19 microM, respectively. The method was successfully applied to the studies of age- and sex-related differences of brain NMT activity in rats. The enzyme activity decreased gradually between 3 and 14 weeks of age whereas there were no differences between males and females in the levels of NMT activity. PMID- 8364476 TI - Stereoselective disposition of pranoprofen, a nonsteroidal antiinflammatory drug, in rabbits. AB - The stereoselective disposition of pranoprofen, a nonsteroidal antiinflammatory drug, was studied in rabbits. Plasma levels of S(+)-pranoprofen after oral and i.v. administration of the racemate pranoprofen were always higher than those of the R(-)-isomer. The elimination rate constant of the R(-)-isomer (2.74 h-1), calculated using a 2-compartment model, was significantly larger than that of the S(+)-isomer (2.14 h-1), while no significant difference was observed in the absorption rate constants between enantiomers. Pranoprofen was excreted in the urine exclusively in the form of pranoprofen glucuronide. The glucuronide of R(-) isomer was excreted more rapidly than the S(+)-isomer. However, no metabolite of pranoprofen was detected in plasma, owing to its instability in liver and plasma. Moreover, the elimination of the S(+)- and R(-)-isomers of pranoprofen was more rapid when the enantiomers were separately administered than when administered as the racemate. The R(-)-isomer showed a significantly higher elimination rate than the S(+)-isomer, compared to what was observed upon the administration of the racemate. No inversion to an R(-)-form or S(+)-form to their corresponding antipode after administration of the isomers separately was detected. Pranoprofen, especially the R(-)-isomer, was significantly distributed in the kidney. An in vitro metabolism experiment of pranoprofen showed the predominant glucuronidation to be in the kidney rather than in the liver because of rapid hydrolysis of glucuronide in the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364478 TI - Analysis of chondroitin sulfate/dermatan sulfate chains in rat peritoneal resident macrophages. AB - Chondroitin sulfate/dermatan sulfate (CS/DS) hybrid polymers obtained from rat peritoneal resident macrophages were analyzed by the enzymatic method; CS/DS chains were digested by chondroitinase, and the resultant unsaturated disaccharides were determined by HPLC with fluorometric detection. CS/DS in the resident macrophages are constituted of Di-4S, Di-6S, Di-diSE, Di-diSB and Di triS. PMID- 8364479 TI - Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. IX. Anti-inflammatory activity of completely alkylated heavy chain (C.Fr.I-H). AB - The anti-inflammatory activity of completely reduced and carboxamide-methylated heavy chain of all disulfide bonds in human serum immunoglobulin G (IgG) (C.Fr.I H) was investigated using some experimental inflammatory models. C.Fr.I-H significantly inhibited carrageenin-induced paw edema and pleurisy, and serotonin induced paw edema. The carboxamide-methylated heavy chain of interchain disulfide bonds in IgG (Fr.I-H) exhibited similar inhibitory activities to C.Fr.I-H on carrageenin-induced paw edema and pleurisy, while it was ineffective on serotonin induced paw edema. These results suggest that complete alkylation of disulfide bonds in a heavy chain caused stronger anti-inflammatory activities than partial alkylation. PMID- 8364480 TI - Effect of pretreatment of skin with cyclic monoterpenes on permeation of diclofenac in hairless rat. AB - The promoting effect of d-limonene and l-menthol on the percutaneous absorption of nonionized and ionized diclofenac (DF) was investigated employing a pretreatment method. After the pretreatment of hairless rat skin with an ethanol buffer solution containing terpenes, the permeation study was performed in vitro. The permeability coefficients of nonionized (Pn) and ionized diclofenac (Pi) were calculated under the assumption that the total flux was composed of individual fluxes of nonionized and ionized DF. In the case of pretreatment with d-limonene, both Pn and Pi values were increased dramatically. However, the promoting magnitude was not affected by an extension of the pretreatment period. In contrast, when the skin was pretreated with l-menthol, the Pn and Pi values increased gradually as the pretreatment period increased. Based on the measurement of the solubility of terpenes in the pretreatment solution, the difference in promoting efficiency could arise from the difference in thermodynamic activity of the terpenes. PMID- 8364481 TI - Rectal absorption of acyclovir in rats and improvement of absorption by triglyceride base. AB - The rectal absorption of acyclovir has been evaluated after administration of suppositories without absorption enhancers in rats. The disappearance of plasma acyclovir followed biexponential kinetics after i.v. dosing. Rectal administration of a triglyceride (Vosco S-55 and Vosco S-55 + methylcellulose) suppository gave relatively high plasma concentrations and bioavailabilities (95.3 and 83.4%, respectively) compared with Witepsol and macrogol suppositories. However, the in vitro release profiles from suppositories did not accurately reflect plasma concentrations after rectal dosing. Our results suggest that the rectal administration of acyclovir suppositories may be a promising substitute for intravenous infusion, which is at present used for the treatment. PMID- 8364482 TI - Evaluation of bioavailability upon oral administration of phytonadione preparations in beagle dogs. AB - Bioavailability of phytonadione was investigated after oral administration to beagle dogs. The administrations of phytonadione in a surfactant solution (preparation a) and in an oleic acid solution (preparations b) greatly increased the bioavailability of phytonadione. The AUCs of preparations a and b were about 2.5 times larger than those of commercially available tablets A and C. This result well corresponded to the results of the dissolution test previously reported. The absorption of phytonadione from the gastro-intestinal tract was affected by food and the bioavailability was largely increased under non-fasted conditions. However, a large scatter was observed in the data, and it was found that the evaluation of the bioavailability of phytonadione preparations could not be done in non-fasted animals. PMID- 8364483 TI - Chemical and biological degradation of 5-fluorouracil prodrugs having high serum albumin binding potencies. AB - In order to understand the fundamental structural features which yield both high serum albumin binding potency and desired property as a prodrug, the derivatization was performed at N-1 or N-3 position in 5-fluorouracil. The N-3 derivatives were more stable than N-1 derivatives in vitro, whereas they were metabolized quickly in vivo. It is suggested that N-1 position should be blocked to avoid fast metabolism in vivo. PMID- 8364484 TI - An acute and focal osteopenia model using ovariectomized rats: a rapid detection of the protective effect of salmon calcitonin. AB - A screening method for anti-osteoporotics using ovariectomized rats was designed using a compact method to monitor the bone density. It was found that ovariectomy (OVX) of Wistar female rats (11 weeks old) induced acute and focal osteopenia within 2 weeks, which responded well to intermittent salmon calcitonin (SCT: 5 and 20 U/kg, s.c., every other day) employed as the standard anti-osteoporotic and injected up to 4 weeks with or without a delay of 2 weeks after OVX. PMID- 8364485 TI - Labile 50S ribosome from partial macrolide-resistant Staphylococcus aureus. AB - Staphylococcus aureus S704 and 8325MMT7 show constitutive resistance to macrolide antibiotics such as erythromycin (EM), oleandomycin, spiramycin, rosamicin and josamycin, except for tylosin, rokitamycin (RKM), and mycinamicin as well as lincosamide and streptogramin type B antibiotics (PM-resistance). Whenever 70S ribosomes from either of them were dissociated into 30S and 50S subunits in a 10 28%(W/W) linear sucrose gradient, the latter subunit was further cleaved into two small apparently equal particles (about 40S). RKM could no longer bind to either of the small particles. A prior exposure of 8325MMT7's 50S subunit to RKM (except EM) did not cause cleavage in any small particles. The largest component (M.W. 33.0kDa) of 50S ribosomal proteins was absent in at least the small particles. The first finding suggests that the lability of the 50S ribosome may be responsible for PM-resistance. PMID- 8364487 TI - Proton NMR study on a histone-like protein, HU alpha, from Escherichia coli and its complex with oligo DNAs. AB - It was confirmed that the flexible arm region of HU alpha forms an antiparallel beta-sheet and that all of the residues of phenylalanines, together with some of leucines and/or valines, form a hydrophobic core within the dimer of HU alpha. HU alpha protein alone is thermally labile and melts at 38 degrees C, but it becomes remarkably stabilized and melts at 59 degrees C in the presence of DNA. Several resonances from both HU alpha and DNA perturbed by their complex formation, notably those of His C-2 and C-4 protons, downfield shifted C alpha protons in the antiparallel beta-sheet, as well as Arg C delta and Lys C epsilon protons. The results indicated that a beta-sheet region of HU alpha binds to DNA, and also showed that rapid equilibrium occurs on the NMR time scale between bound and unbound states of HU alpha. A few intermolecular nuclear Overhauser effects (NOEs) were also observed between the protein and H1' protons of DNA in the complex, suggesting that HU alpha binds primarily to the minor groove of DNA. PMID- 8364486 TI - Inhibitory effect of diltiazem on diazepam metabolism in the mouse hepatic microsomes. AB - In order to elucidate the drug interaction between diltiazem and diazepam, the effect of diltiazem on the N-demethylation of diazepam in the mouse hepatic microsomes was investigated. Kinetic study showed that diltiazem noncompetitively inhibited the N-demethylation of diazepam with inhibition constant (Ki) value of 247.8 microM, indicating that diltiazem exhibits an inhibitory effect on the hepatic oxidative metabolism of diazepam. It was therefore suggested that diltiazem may impair the metabolism of diazepam in vivo. PMID- 8364488 TI - Purification of water-soluble bone-inductive protein from bovine demineralized bone matrix. AB - The water-soluble fraction containing bone-inductive activity was purified from guanidine-hydrochloride extracts of bovine demineralized bone. The purification steps include ultrafiltration, dialysis, affinity chromatography on heparin Sepharose and gel chromatography on Sephacryl S-200. Combination of these steps was proven to be an effective and rapid method for the purification of this protein. Subcutaneous implantation of the water-soluble protein with type I collagen was carried out in the thorax of rats. When alkaline phosphatase activity and calcium content in implants were used as indices for purification, the water-soluble bone-inductive protein was purified > 600-fold according to the enzyme activity and 64-fold according to the calcium content. A morphological examination revealed that many chondrocyte and osteoblast cells were seen in the location of the implanted material. Sodium dodecyl sulfate/gel electrophoresis of the protein produced in this way under non-reducing conditions revealed four protein bands of 18, 16, 14 and 11 kDa. None of the separated bands had any biological activity. This result suggests that the water-soluble bone-inductive activity depends on an associated form of various proteins in the range of 18 to 11 kDa. PMID- 8364489 TI - Sialic acid in fibrinogen: effects of sialic acid on fibrinogen-fibrin conversion by thrombin and properties of asialofibrin clot. AB - The final stage in a series of blood coagulating reactions is fibrinogen-fibrin conversion by thrombin. This reaction consists of fibrinopeptide A and fibrinopeptide B release, polymerization of fibrin monomer, and stabilized fibrin formation by factor XIII. The latter two reactions require calcium. In the present study there was no difference in the rate of thrombin-induced fibrinopeptide release between fibrinogen and asialofibrinogen where sialic acid in the terminal end of carbohydrate moiety of fibrinogen was removed by neuraminidase, but turbidity associated with asialofibrin clot formation was increased more rapidly. In asialo-derivatives, the dissolution time of the clots in high concentrated urea solution tended to be shortened and rigidity as a gel tended to be decreased. In measurement by thromboelastography there was no difference in the reaction time (r) between fibrinogen and asialofibrinogen, but the maximum amplitude (ma) was obviously decreased in asialofibrinogen. Furthermore, when the rate of cross-link formation between gamma chains by F-XIII was compared, the production of gamma-dimer in the same reaction time was found to be lower and formation of stabilized fibrin tended to be retarded in asialofibrinogen. Sialic acid in fibrinogen thus may clearly influence the polymerization of fibrin-monomer and the formation of cross-linked fibrin in a series of reactions for fibrinogen-fibrin conversion. This may be consistent with the theory that fibrinogen sialic acid residues are low affinity calcium-binding sites and influence fibrin assembly. PMID- 8364490 TI - Characterization of capacitation inhibitory protein from rabbit seminal plasma: homology with human annexins. AB - A protein was purified from rabbit seminal plasma using preparative acrylamide disc electrophoresis, ammonium sulfate precipitation and gel filtration. The protein inhibited the in vitro fertilization of mouse ova inseminated with epididymal sperm and with capacitated sperm. The inhibition was not observed, however, when only ova were exposed to the protein prior to mixing with sperm. The partial protein sequence analysis revealed the strong homology of the rabbit fertilization inhibitory protein to human annexin V. PMID- 8364491 TI - Influence of liposomes on tryptic digestion of insulin. AB - The influence of phosphatidylcholine liposomes on the tryptic digestion of insulin was studied to obtain basic information on the interaction between liposomes and peptides or proteins. Protection of insulin from tryptic digestion by liposomes depended on the encapsulation efficiency and the method of preparation of liposomes. REV (reverse phase evaporation vesicles) were most effective for the protection of insulin from tryptic digestion. Tryptic digestion of insulin was accelerated by negatively-charged liposomes (containing 10% phosphatidylserine, phosphatidylinositol, or phosphatidic acid) or by neutral empty liposomes, this digestion being enhanced by progressively smaller liposome size (from 2 to 0.1 microns) in the case of neutral empty liposomes. These results suggest that this enhancement had occurred on the surface of the empty neutral or negatively-charged liposomes. Positively-charged empty liposomes (containing 10% of stearylamine) weakly suppressed the tryptic digestion of insulin. The size of the positively-charged liposomes increased after the addition of insulin, this size increase suggesting that these liposomes were fused by insulin. Presumably, insulin was protected by the lipids around the insulin molecule after the insulin-induced fusion or aggregation of positively charged liposomes. PMID- 8364492 TI - Inhibitory effect of beta-glucans on zymosan-mediated hydrogen peroxide production by murine peritoneal macrophages in vitro. AB - Effects of the pretreatment of murine peritoneal macrophages with several polysaccharides on the production of H2O2 induced with unopsonized zymosan were examined. Pretreatment with most of (1-->3)-beta-D-glucans for 6 h at 37 degrees C inhibited the zymosan-mediated H2O2 production by macrophages. The phorbol myristate acetate (PMA)-mediated H2O2 production was not affected by the pretreatment. The pretreatment of macrophages with (1-->3)-beta-D-glucans decreased the ability to ingest unopsonized zymosan, but did not affect the ingestion of IgG-coated sheep red blood cells (IgG-SRBC). These results suggested that the pretreatment with (1-->3)-beta-D-glucans interfered with the interaction of macrophages to zymosan and that the occupation of the receptor for the (1-->3) beta-D-glucans inhibited zymosan-mediated production of H2O2 by macrophages. Chemical modification by substitution with carboxymethyl groups or hydroxyethyl groups of a (1-->6)-branched (1-->3)-beta-D-glucan reduced the inhibitory effect of pretreatment on zymosan-mediated H2O2 production. The above results indicated the possibility that murine peritoneal macrophages possess certain receptors for beta-anomeric glucans, and one ligand specificity of the receptors is to restrict the intact (1-->3)-beta-D-glucosyl back bone. PMID- 8364493 TI - Effects of insulin and 1 alpha-hydroxy vitamin D3 on streptozotocin-induced diabetic rats fed a low zinc diet. AB - Streptozotocin-induced diabetic rats (LZ-DM rats) developed nephrocalcinosis after being fed a low zinc diet for 4 weeks. However, administration of 1 alpha hydroxy vitamin D3 (1-OHD3) or insulin inhibited the formation of nephrocalcinosis. The urinary calcium level increased when 1-OHD3 was administered to these rats, but decreased in the group receiving insulin. It was also observed that the femur recovered its hardness when insulin was administered, although the hardness in the LZ-DM rats remained lower than that of the control rats. Rat femur hardness, however, did not completely recover with 1 OHD3 treatment. These results indicate that the effects of insulin and 1-OHD3 differ, even though nephrocalcinosis was reduced by administration of either insulin or 1-OHD3. It appears that insulin assists bone formation, and the 1-OHD3 hastens calcium excretion. PMID- 8364494 TI - Effect of benidipine hydrochloride (KW-3049), on cerebral ischemia induced by bilateral occlusion of the common carotid arteries in rats. AB - The effect of benidipine on experimental cerebral ischemia was investigated in rats subjected to occlusion of the bilateral common carotid arteries. Benidipine (30 micrograms/kg, i.p.) improved neurological symptoms such as ataxia, convulsion and loss of righting reflex, and prolonged survival time after occlusion of the bilateral common carotid arteries. In the nicardipine (100 micrograms/kg, i.p.)-treated group, a similar effect was observed, whereas nifedipine (100, 300 micrograms/kg, i.p.) and verapamil (300 micrograms/kg, i.p.) did not show any beneficial effect in this model. Furthermore, pretreatment with benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content 3 h after the occlusion. Nicardipine (100 micrograms/kg, i.p.) showed a tendency to reduce the increase in cerebral water content, though the effect was not statistically significant. Nifedipine (100 micrograms/kg, i.p.) produced no improvement. After occlusion of the bilateral common carotid arteries, depletion of adenosine triphosphate (ATP) and phosphocreatine (CP) and an accumulation of lactate occurred in a time-dependent manner. Prophylactic administration of benidipine (30 micrograms/kg, i.p.), 20 min before occlusion, attenuated the depletion of ATP and CP and the accumulation of lactate 3h after the occlusion. Furthermore, post-treatment with benidipine 30 min after occlusion also suppressed these metabolic disorders. In conclusion, the beneficial effects of benidipine in this severe cerebral ischemia model show that the compound has advantages over nicardipine, nifedipine and verapamil. Thus, these results suggest that benidipine may be useful in the treatment of acute ischemic cerebral damage. PMID- 8364495 TI - Inhibition by indomethacin of the already accelerated secretion of inhibin and estradiol in equine chorionic gonadotropin-primed immature female rats. AB - In immature female rats, the secretion of ovarian inhibin and estradiol is greatly accelerated by equine chorionic gonadotropin (eCG) treatment. The present study has been carried out to determine whether or not the levels of the two hormones are inhibited by a single s.c.-injection of indomethacin (INDO) 24 h after eCG administration. The levels of ovarian hormones and gonadotropins were measured by double-antibody radioimmunoassay using 125I-labeled radioligands. The serum levels of inhibin and estradiol were considerably inhibited within 24 and 12 h, respectively, after INDO injection. In addition, the serum levels of follicle-stimulating hormone (FSH) after INDO injection remained lower than the basal levels before eCG treatment. The luteinizing hormone (LH) levels were significantly reduced within 12 h after INDO treatment. The results demonstrate that the levels of inhibin and estradiol, even in the situation where the production of both hormones is already accelerated by eCG pretreatment, are suppressed by an inhibitor of prostaglandin (PG) synthesis, suggesting that locally produced PGs may play a role in the regulation of the production of both hormones in the ovary. PMID- 8364496 TI - Preventive effect of beta-alanyl-L-histidinato zinc on the deterioration of bone metabolism in ovariectomized rats. AB - The preventive effect of beta-alanyl-L-histidinato zinc (AHZ) on the deterioration of bone metabolism was investigated in the femoral diaphysis of ovariectomized rats. AHZ (10, 30 and 100 mg/kg body weight/d) was orally administered to ovariectomized rats for 6 weeks. Ovariectomy produced a significant decrease in estradiol, calcitonin, calcium and inorganic phosphorus concentrations in the serum as compared with those from sham-operated rats. The dose of 30 and 100 mg AHZ/kg prevented any decrease in serum inorganic phosphorus concentration caused by ovariectomy. Alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the femoral diaphysis of ovariectomized rats significantly decreased in comparison with those from sham operated rats. These decreases were completely prevented by the dose of AHZ (10, 30 and 100 mg/kg). Electron microscopical analysis showed a rough alteration of bone matrix in the femoral diaphysis of ovariectomized rats. This alteration was clearly modified by the doses of AHZ (10, 30 and 100 mg/kg). Also, dosages of AHZ (30 and 100 mg/kg) restored the atrophy of osteoblasts and cartilage cells caused by ovariectomy. The present study suggests that oral administration of AHZ can prevent the deterioration of bone metabolism by ovariectomy. AHZ may have a therapeutic role in the treatment of osteoporosis. PMID- 8364497 TI - Expression of the Na+ dependent uridine transport system of rabbit small intestine: studies with mRNA-injected Xenopus laevis oocytes. AB - Xenopus laevis oocytes were used as an expression system to prove and characterize the carrier-mediated transport of uridine in the small intestine. Significant Na+ dependency was observed for the uptake of [3H]uridine by Xenopus laevis oocytes injected with poly(A)+RNA prepared from rabbit small intestinal mucosa. By contrast, the uptake of [3H]uridine was negligible in water-injected oocytes. There was no significant difference in the Na+ dependent uptake rates of [3H]uridine among oocytes expressed by using mRNA prepared by three different methods. The uptake of [3H]uridine by mRNA-injected oocytes was enhanced by increasing the culturing time after mRNA injection. Concentration dependency for uridine transport was observed with the Michaelis constant of 8.27 microM, which was comparable to that reported in the study using the brush-border membrane vesicles from rabbit small intestine (6.4 microM). Furthermore, the uptake of [3H]uridine was significantly inhibited by adenosine and thymidine, but not by adenine and uracil. Consequently, the transport system of uridine expressed in mRNA-injected oocytes is clarified to be similar to that functioning in the brush border membrane of the small intestine. PMID- 8364498 TI - Uptake mechanism of fractionated [3H]heparin in rat parenchymal hepatocytes in primary culture: effect of transport inhibitors on the uptake. AB - In order to elucidate the uptake mechanism of fractionated [3H]heparin by rat parenchymal hepatocytes, the concentration dependent uptake was kinetically analyzed in primary culture of rat parenchymal hepatocytes, and the effects of established transport inhibitors and heparin analogues on the uptake were also examined. The uptake rate of heparin measured over an extended period of 60 min was saturable, with the maximum uptake velocity (Vmax) of 0.36 +/- 0.05 pmol/min/mg protein and the Michaelis constant (Km) of 21.2 +/- 5.4 nM. The uptake was inhibited by the addition of 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS), an inhibitor of the anion transport system, and rose bengal, an organic anion. Heparin analogues (pentosan polysulphate, or heparan sulphate) also inhibited the uptake of fractionated heparin. However, the uptake was not inhibited by the inhibitors of receptor-mediated endocytosis (phenylarsine oxide). These results suggest that fractionated heparin may be taken up by anion transport system, rather than by receptor-mediated endocytosis, though the fractionated [3H]heparin is a compound with the high molecular weight of about 20000 Da. At least the negative charge or sulphate group in the drug structure is supposed to play an important role in the uptake of fractionated heparin by parenchymal hepatocytes. PMID- 8364499 TI - Population pharmacokinetics of theophylline. II: Intravenous infusion to patients with stable chronic airway obstruction. AB - The population pharmacokinetics of theophylline were studied in 55 patients with stable chronic airway obstruction. Two hundred and seventy six theophylline serum concentrations after intravenous short infusion were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, smoking habit, age and the measurement of arterial blood gases (oxygen tension: PaO2, carbon dioxide tension: PaCO2, blood pH) and clinical laboratory tests (serum albumin concentration, haematocrit) on the pharmacokinetic parameters of theophylline was examined by the likelihood ratio test. Assessment of each factor was made by a forward selection method. In the final regression model, the total body clearance (CL, l/h/kg) was related to the value of PaCO2 as well as to the presence of hepatic dysfunction, and the volume of distribution (Vd, l/kg) was related with the PaCO2 value as expressed in the following equations: CL = exp(-3.78 - 0.525.HF + 0.0233.PaCO2) and Vd = exp(-1.12 + 0.00934.PaCO2), where HF is a categorical variable with a value of unity if a patient has hepatic dysfunction otherwise zero. The interactions among blood gas measurements were observed and the CL and Vd of theophylline would be inversely correlated with PaO2 or pH, if we selected PaO2 or blood pH to be a more important factor than PaCO2. The inter individual variabilities in CL and Vd were 38.5% and 12.5%, respectively, and the residual variability in theophylline serum concentrations was 10.6% as a coefficient of variation. This final model and the population parameters of theophylline will be useful for individualization of a drug dosage regimen by means of the Bayesian method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364500 TI - Effect of spacer groups connecting insulin with fluorophore in Gly(A1) sulfobenzoxadiazole-labeled insulins on the immunoreactivity toward anti-insulin antibody. AB - The immunoreactivity (specific binding) of three Gly(A1)-sulfobenzoxadiazole labeled insulins which have different spacer groups, Gly(A1)-[3-(4 sulfobenzoxadiazol-7-ylthio)propanoyl]-insulin , Gly(A1)-[2-(4-sulfobenzoxadiazol 7-ylthio)acetyl]-insulin, Gly(A1)-[3-carboxy-2(or 3)-(4-sulfobenzoxadiazol-7 ylthio)propanoyl]-insulin, toward an antiporcine insulin monoclonal antibody was investigated, where solid-phase fluoroimmunoassay technique was utilized. The immunoreactivities of three labeled insulins were 2.1, 1.8 and 1 in that order. PMID- 8364501 TI - Influence of dietary lipids on glucuronidation and sulfation of phenol and its para substituent in the rat. AB - Rats were fed corn oil-free or corn oil-containing diets for 4 weeks to determine their effect on the competition between glucuronidation and sulfation in phenol and its para substituents. The activities of uridine diphosphate glucuronyltransferase (UDPGT) on chemicals were enhanced with a 12% corn oil diet, whereas sulfotransferase activity showed no significant change. Following the intravenous injection of p-ethylphenol and p-tert-butylphenol, an increase of glucuronide and a decrease of sulfate were observed in the rats fed the corn oil diet. In contrast, no significant changes were observed in phenol and p phenylphenol. These results are discussed in association with van der Waals volume (Vw) of substituent and phospholipid dependence of UDPGT. PMID- 8364502 TI - Cytotoxic effect of hinokitiol and tropolone on the growth of mammalian cells and on blastogenesis of mouse splenic T cells. AB - Hinokitiol (I) and tropolone (II) showed characteristic cytotoxic effects in vitro on five kinds of human and murine cell lines and blastic lymphocytes from mouse splenocytes. The cytotoxic effect of I on the growth of murine and human tumor cell lines, including RL male-1, MH134, HL60, K562 and KATO-III was definite when examined by thymidine incorporation into DNA and its 50% inhibitory concentration (IC50) on all cells was 0.3-0.6 microgram/ml. Compound II also showed comparable cytotoxic effects on these cell lines, indicating a little lower activity when compared to I. Furthermore, I and II also completely suppressed the [3H]thymidine ([3H]TdR) incorporation of mitogen-induced blastic lymphocytes. The suppressive activity on mouse lymphocyte proliferative response to concanavaline-A was also found with both compounds at a low concentration of 0.32 microgram/ml. As compound I is known to be of fairly low toxicity (LD50: 453 + 24 mg/kg in mice), the antitumor and immuno-suppressive effect of hinokitiol (I) should be further investigated. PMID- 8364503 TI - Nucleosides and nucleotides. CXIX. Inhibition of DNA-cytosine methylase HhaI by a self-complementary oligonucleotide containing 5-fluorocytosine. AB - A self-complementary decadeoxyribonucleotide, 5'd(GAAGFGCTTC)3', containing 5 fluorocytosine (F) in substitution for cytosine at the methylation site of DNA cytosine methylase HhaI (MHhaI) has been synthesized. MHhaI was inhibited by the pre-incubation of the enzyme with d(GAAGFGCTTC). PMID- 8364504 TI - Evidence for serum factors modulating antibody production in normal and macular mice. AB - The macular mutant mouse is a model of Menkes' kinky hair disease, which is characterized by a deficiency of ceruloplasmin in the serum. In hemizygotic mice (ml/y), the antibody production against sheep red blood cells (SRBC) was decreased. Treatment with normal (+/y) mouse serum increased in a dose-dependent manner the antibody response of ml/y mouse spleen cells in vitro. However, +/y mouse serum had no effect on +/y mouse spleen cells, even at high doses up to 5%. In contrast, ml/y mouse serum decreased antibody production in +/y mouse spleen cells in a dose-dependent manner. Antibody production in +/y mouse spleen cells decreased with time, after pretreatment with ml/y mouse serum. However, serum from ml/y mice injected with ceruloplasmin did not decrease antibody production in +/y mouse spleen cells but rather increased it in ml/y mouse spleen cells. Ceruloplasmin had no effect on the production of antibodies against SRBC in ml/y and +/y mouse spleen cells in vitro. These findings suggest that one or more enhancers of antibody production exist in normal mouse serum and that one or more suppressors of normal antibody production exist in ml/y mouse serum. It is proposed that the activities of these factors in serum may be regulated by ceruloplasmin. PMID- 8364505 TI - Capillary gas chromatography quantification of cholesterol in copper-oxidized low density lipoprotein. AB - A simple analytical method, using capillary gas chromatography-mass spectrometry (GC-MS) was used to investigate the oxidative modification of cholesterol in copper-oxidized low-density lipoprotein (oxidized LDL). The incubation of LDL and 5 microM CuSO4 in 0.15 M NaCl/0.02 M Tris-HCl buffer at pH 7.4 led to the peroxidation of LDL as shown by the detection of a thiobarbituric acid-reactive substance (TBA-RS). Oxidized LDL was shown to cause a significant fall in the unesterified and esterified cholesterol content, while oxysterols such as 7 hydroxycholesterol (7-OH) and 7-ketocholesterol (7-Keto) were formed from cholesterol, these conversions occurred in a dose- and time-dependent manner. Both oxysterols were identified by GC-MS on a fused-silica capillary column. In addition, copper-oxidized high-density lipoprotein (oxidized HDL) also resulted in the generation of TBA-RS and oxysterols. In addition, changes in the composition and amount of oxysterols during the incubation of macrophages with oxidized LDL were investigated. The incubation of macrophages with oxidized LDL resulted in the accumulation of cholesterol, 7-OH and 7-Keto derivatives in macrophages and this accumulation also occurred in a dose-dependent manner. These results suggest that the measurement of oxysterols may afford an additional index of oxidized LDL, and that foam cell formation and early atherosclerotic lesions may be responsible for the accumulation of oxysterols in macrophages. In addition, this study shows that HDL is also modified when submitted to an oxidative process. PMID- 8364506 TI - Interaction of a protein-bound polysaccharide (PSK) with chicken gizzard caldesmon. AB - The interaction of a protein-bound polysaccharide (PSK) with caldesmon was studied in detail using sedimentation, low-shear viscometry, electron microscopy and affinity chromatography. The binding of caldesmon to F-actin was concentration-dependently inhibited by PSK. Bundle formation of actin filaments owing to caldesmon was also inhibited by PSK. Caldesmon bound to a PSK-Sepharose 4B column at low ionic strength was released at about 400 mM NaCl, whereas G actin was not retained by the column. Treatment of caldesmon with chymotrypsin produced major fragments near 100, 80, 60, 38 and 25 kDa. In contrast, 60 and 25 kDa fragments were rarely formed by this treatment in the presence of PSK. Fragments of 80 and 38 kDa, major products produced by chymotrypsin, bound individually to a PSK-Sepharose column, indicating that caldesmon has at least two binding sites for PSK. Addition of calcium and calmodulin partially released caldesmon from actin filaments. PSK-dependent release of caldesmon was also observed in the presence of calcium and calmodulin. PMID- 8364507 TI - A trypsin inhibitor trans-4-guanidinomethylcyclohexanecarboxylic acid 4-tert butylphenyl ester suppresses the onset of DNA synthesis in Escherichia coli cells synchronized by phosphate starvation. AB - trans-4-Guanidinomethylcyclohexanecarboxylic acid 4-tert-butylphenyl ester (GMCHA OPh'Bu), a trypsin inhibitor, dose-dependently inhibited the growth of Escherichia coli K-12 IAM1264. Growth inhibition was preceded by dose- and time dependent inhibition of DNA synthesis. These results strongly suggested participation of a trypsin-like proteinase in DNA synthesis. To clarify this suggestion, the effects of GMCHA-OPh'Bu on the doubling time and on the uptake of [methyl-3H]thymidine into DNA were examined with E. coli K-12 IAM1264 synchronized by a modified version of phosphate starvation. The synchrony lasted for two or three cycles with a doubling time of 55 min and a cell division period of 15 min. The cell cycle of E. coli was divided into three periods, cell division period (P), the period between cell division and initiation of chromosome replication (Q) and the period between initiation of chromosome replication and cell division (R). The R period was subdivided into two periods, R1 in which the rate of thymidine uptake into DNA was increasing, and R2 in which it was constant. The addition of GMCHA-OPh'Bu at the R1 period did not affect the already-initiated round of cell division, however, it retarded the next round. The addition at P, Q or R2 retarded the cell division in the same round, causing prolongation of the R1 period. A sharp and momentary appearance of trypsin-like proteinase activity peaked at the Q/R1 boundary in one cell cycle, and inhibition of the activity prolonged the R1 period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364508 TI - Amidinopiperidine-4-carboxylic acid 4-tert-butylphenyl ester, a trypsin inhibitor, suppresses the onset of DNA synthesis in HeLa cells synchronized by a double-thymidine block. AB - Release of HeLa cells arrested at the G1/S boundary by double-thymidine block caused abrupt uptake of [methyl-3H]thymidine into DNA after 5 min, and two sharp high activity peaks, peak I and peak II, were observed 8 and 23 min after removal of the thymidine block and this was followed by a gradual uptake of [3H]thymidine. The duration of the cell cycle was 23 h, and definite changes in cell density were observed between 12 and 13 h and also between 35 and 36 h after removal of the thymidine. Addition of amidinopiperidine-4-carboxylic acid 4-tert butylphenyl ester (APCA-OPh'Bu), a trypsin inhibitor, immediately after removal of the arrest strongly suppressed DNA synthesis and mitosis. In contrast, addition of APCA-OPh'Bu 10 min after removal of the arrest, and hence also after the appearance of peak I, had no effect on peak II nor on the uptake of thymidine occurring during the remainder of the first cell cycle, nor on mitosis. However, it strongly suppressed the second DNA synthesis and mitosis. These results suggest participation of a trypsin-like proteinase at the onset of DNA synthesis. Removal of thymidine from the arrested cells at a cell density of 2% (4 x 10(3) cells/cm2) induced an immediate and rapid rise in trypsin-like proteinase activity. However, the activity decreased with increasing cell density. No clear increase in the activity was seen at a cell density of 20% (4 x 10(4) cells/cm2). However, both trypsin-like proteinases obtained at cell densities of 2% and 20% were strongly inhibited by APCA-OPh'Bu and these inhibitory effects were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364510 TI - A novel metabolite of 3,4-methylenedioxyamphetamine (MDA): formation of 3-methyl 6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline and its pharmacological effect. AB - In 3,4-methylenedioxyamphetamine (MDA)-treated rat brain and urine, 3-methyl-6,7 methylenedioxy-1,2,3,4-tetrahydroisoquinoline (3Me6,7MDTIQ) was detected as a new metabolite. The content of 3Me6,7MDTIQ in (R)-MDA-treated rat was significantly higher than that in (S)-MDA-treated brain and urine. This result suggests that this metabolism of MDA contains stereoselective pathways. The pharmacological effects of 3Me6,7MDTIQ on behavior differed from those of MDA. The ambulation score of 3Me6,7MDTIQ was significantly decreased compared to the control, and the rearing score of 3Me6,7MDTIQ was moderately decreased compared to the control in an open-field test. PMID- 8364509 TI - Studies on cytochrome P450 responsible for oxidative metabolism of imipramine in human liver microsomes. AB - The activity of imipramine 2-hydroxylase highly correlated with that of desipramine 2-hydroxylase but not with that of desipramine N-demethylase. The correlation was also found between N-demethylation and 2-hydroxylation when imipramine was used as a substrate, whereas no correlation was observed between them when desipramine was used in place of imipramine. Both activities of desipramine and imipramine 2-hydroxylase were markedly inhibited by quinidine but not by quinine. Although the activity of imipramine N-demethylase was slightly inhibited by both quinidine and quinine, the activity of desipramine N demethylase was unaffected under the same conditions. The activity of imipramine N-demethylase was roughly correlated with the amounts of P450 3A4 immunochemically determined and the activities of testosterone 6 beta-hydroxylase in human liver microsomes. The P450 3A4 catalyzed imipramine N-demethylation much more efficiently than 2-hydroxylation in a reconstituted system, whereas neither N-demethylation nor 2-hydroxylation of desipramine was catalyzed by P450 3A4. The activity of imipramine N-demethylase was inhibited, to various extents, by anti P450 3A4 antibodies in human liver microsomes. Taking together these and other results, it is suggested that P450 3A4, other than P450 2Cmp, also partly contributes to N-demethylation of imipramine, depending on human liver microsomes. PMID- 8364511 TI - Percutaneous absorption of acemetacin from a membrane controlled transdermal system and prediction of the disposition of the drug in rats. AB - To avoid development of a lesion on the small intestine by acemetacin (ACM) following oral administration of the drug, we developed a new device for its percutaneous application. The device for transdermal application of ACM consisted of a silicon O-ring, a backing of aluminum foil and adhesive tape, and rate controlling membranes with three different pore sizes (HP-1100, 2100 and 4050). Two percent ACM gel ointment was contained in the device. In the in vitro release experiment, the ACM release from the device was limited by these membranes with release rate constants of 0.630 +/- 0.052, 0.289 +/- 0.012, 0.098 +/- 0.11 and 0.083 +/- 0.011 h-1 for no membrane, HP-4050, HP-2100 and HP-1100 membranes, respectively. In the in vitro penetration experiment, the ACM penetrating through the skin appeared in the reservoir cell without the metabolic conversion to indomethacin (IM). After the application of the ACM device with the HP-2100 rate controlling membrane on the rat abdominal skin, ACM was not detected in the plasma but the therapeutic plasma concentration of IM could be maintained over a 54 h period. These results indicate that the device with a rate-controlling membrane may be useful for the percutaneous application of ACM as an anti inflammatory drug and its clinical application. For the percutaneous absorption of ACM after application of the ACM devices, the values estimated by the proposed model which consisted of 6 compartments well fit to the data obtained from this in vivo experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364512 TI - Two-layer membrane model for iontophoretic drug transport through excised rat skin. AB - Iontophoretic and passive transport of an ionized drug (sulfisoxazole) across excised rat skin was studied using a two-chamber cell with four electrodes under successive experimental conditions: without electrical current (stage-I) and with electrical current (stage-II). Two iontophoretic/diffusion models, i.e. a one layer membrane model and a two-layer membrane model, in which a difference in the electrical potential gradient was taken into account between the stratum corneum and epidermis/dermis layer, were constructed to describe the non-steady-state drug permeation process during ionotrophoresis. The observed iontophoretic lag time was two times greater than the calculated value based on the one-layer membrane model. According to the two-layer membrane model, the calculated ionotophoretic lag-time agreed with the observed value. It was revealed by model adaptation to the observed data that the stratum corneum fraction of the electro chemical potential difference across the whole skin caused by the iontophoresis was around 90%. This result was consistent with the observation that the direct current resistance of whole skin was seven times greater than that of stripped skin. PMID- 8364513 TI - Effects of aluminium-containing antacid on bioavailability of ofloxacin following oral administration of pivaloyloxymethyl ester of ofloxacin as prodrug. AB - We newly synthesized a pivaloyloxymethyl ester of ofloxacin (OFLX-PVM) as prodrug in order to avoid the chelate formation between new quinolone and metal cations such as Al3+, Mg2+, Ca2+, or Fe2+ in the gastrointestinal tract. This compound was rapidly hydrolyzed in an incubation experiment by 43% in plasma, by 92% in small intestinal mucosal homogenates, and by 97% in liver homogenates during 0.5 h incubation, but was resistant to hydrolysis by pancreatic enzymes. In everted gut sac experiments, this compound was efficiently absorbed even in the presence of aluminium ion, whereas the absorption of ofloxacin (OFLX) was decreased significantly by the presence of aluminium ion. Minimal inhibitory concentration (MIC) values of OFLX-PVM were far higher than OFLX. Effects of aluminium hydroxide on the oral bioavailability of OFLX and OFLX-PVM were investigated in rabbits. The area under the plasma concentration-versus-time curve from zero to 24 h (AUC0-24h) following oral administration of OFLX was decreased significantly by 47.6% by combined administration with aluminium hydroxide, but AUC0-24h values of OFLX-PVM coadministered with and without aluminium hydroxide were similar to that of OFLX alone. These observations indicate that this new compound is likely to offer a prodrug for avoidance of interaction between new quinolone and metal cations. PMID- 8364514 TI - Influence of composition of l-menthol-ethanol-water ternary solvent system on the transdermal delivery of morphine hydrochloride. AB - The influence of concentration of each component in l-menthol-ethanol-water ternary solvent system (MEW system) on the skin permeation of morphine hydrochloride (MPH) was investigated in hairless rats. The cumulative amount of MPH permeated through the excised abdominal skin over 8 h (Q-8) was selected as an index of skin permeability. With changing MPH concentration over a wide range from 0.01 to 10% in a MEW system (5% l-menthol and 40% ethanol), the values of Q 8 were proportional to MPH concentration. The concentration was fixed at 1% for the following experiments. For the effect of the concentration of l-menthol at 40% ethanol, the maximum Q-8 was observed at 5% l-menthol, and no greater enhancement of Q-8 was obtained by increasing l-menthol concentration above that. In the ethanol effect at 5% l-menthol, the maximum Q-8 was observed at 45% ethanol. When 2-propanol and methanol, which are more lipophilic and hydrophilic than ethanol, respectively, were used instead of ethanol, the maximum values of Q 8 were observed at 40 and 55%. The maximum values for Q-8 were obtained in the vicinity of the solubility of l-menthol in the MEW system in all cases, suggesting that the skin permeation enhancing effect of the system is dependent on the thermodynamic activity of l-menthol. PMID- 8364515 TI - Pre-column derivatization and its optimum conditions for quantitative determination of urinary hydroxylysine glycosides by high-performance liquid chromatography. AB - A method has been developed for rapid analysis of the urinary hydroxylysine glycosides [glucosyl-galactosyl-hydroxylysine (GGH) and galactosyl-hydroxylysine (GH)] as collagen metabolites. The glycosides were fluorometrically derivatized with 5-dimethylaminonaphthalene-1-sulfonyl chloride, and then subjected to reversed-phase high-performance liquid chromatography using a gradient system. Suitable standard hydroxylysine glycosides which were not diastereoisomers were prepared from human urine. Urinary GGH and GH were analyzed within 1 h, including column washing. This method was applied to the urine samples of 68 healthy persons of different ages. PMID- 8364516 TI - The relationship between induction of peroxisomal beta-oxidation and long-chain fatty acid composition in rat liver. AB - The long-chain fatty acid composition in rat liver, by which peroxisomal beta oxidation system was induced, was analyzed in vitro and in vivo. In primary culture of hepatocytes, treatment with 0.4 mM clofibrate or long-chain fatty acids caused an increase in the peroxisomal beta-oxidation activity, in addition the oleic acid [18:1(n-9)] content in the cells was increased two-fold by addition of very long-chain fatty acids to the culture medium, but clofibrate had no effect. A two-fold of increase in 18:1(n-9) content was observed in the hepatic subcellular fractions from rats fed a diet containing 0.25% clofibric acid. The ratio of cis-vaccenic acid [18:1(n-7)] to total 18:1 content decreased by more than half compared with control in clofibric acid treated liver. The level of 18:1(n-7) was not changed in all experiments. It is suggested that perturbation of C-18 chain length fatty acids occurs in peroxisomal beta oxidation induced liver. PMID- 8364517 TI - Comparative bioavailability study of acetaminophen solutions used in hospital formulary. AB - To learn the influence of polyethylene glycol (PEG) on bioavailability, this study compared the bioavailability of acetaminophen in the presence of 10% ethanol (acetaminophen-ethanol liquid) to that in the presence of 10% PEG (acetaminophen-PEG liquid) since these two preparations are commonly used in hospital formulary. The results in Thai male volunteers showed there was not significantly different. PMID- 8364518 TI - The development of oral vaccines based on live attenuated Salmonella strains. AB - Safe, live attenuated Salmonella strains can be produced by introducing defined non-reverting mutations into the chromosome. Such rationally attenuated strains have proved to be excellent oral vaccines in several animal species and can therefore be considered as candidate vaccines against invasive salmonellosis in both animals and man. A panel of attenuating lesions is now available from which it is possible to tailor the level of attenuation and hence produce strains with different immunogenic properties. Because of the spectrum of immune responses produced by such Salmonella vaccine strains they have been utilised extensively as vectors for delivering heterologous antigens to the mammalian immune system. We have focussed on the development of a single dose oral tetanus vaccine based on attenuated Salmonella strains expressing a non-toxic, immunogenic protein derived from tetanus toxin (fragment C). Several different expression systems have been used for fragment C and candidate vaccine strains have been constructed that are capable of protecting orally immunised mice against a lethal challenge with tetanus toxin. An oral tetanus vaccine may help to reduce the mortality rate from tetanus in the developing world by overcoming the problems associated with the implementation of vaccine programmes using the current parenteral vaccine. PMID- 8364519 TI - In vitro activity of zidovudine alone and in combination with ciprofloxacin against Salmonella and Escherichia coli. AB - The in vitro antibacterial activity of zidovudine alone and in combination with ciprofloxacin was investigated. Zidovudine showed a good activity against Escherichia coli and Salmonella (MIC range 0.5-8 micrograms/ml and 1.5-62 micrograms/ml respectively) isolated from biological samples of HIV-infected patients. These strains proved to be extremely susceptible to ciprofloxacin alone. The interaction between zidovudine and ciprofloxacin ranged from additive activity to indifference. No antagonism was observed: the FIC index for every combination resulted < or = 1.5. The addition of AZT 1 mg/l (clinically achievable plasma concentration after therapeutic doses of 1200 mg/day) did not affect the bactericidal activity of ciprofloxacin; on the contrary, in some cases we observed an increase of bactericidal effect of the quinolone. These data have to be considered in patients with AIDS who can be treated concomitantly with zidovudine and ciprofloxacin. PMID- 8364520 TI - High-affinity binding of laminin by Helicobacter pylori: evidence for a lectin like interaction. AB - Laminin, the major glycoprotein of basement membranes, was shown to be bound by the human gastric pathogen Helicobacter pylori. Binding of 125I-laminin by strain 17874 was time-dependent, specific and saturable. Scatchard analysis of specific binding indicated about 2000 binding sites per cell with a dissociation constant of 8.5 pM. Treatment of the cells by heat (80 degrees) and with proteolytic enzymes drastically reduced laminin binding, suggesting that the laminin receptors are surface proteins. Some highly glycosylated glycoproteins inhibited laminin binding by 50%. Furthermore, N-acetylneuraminyllactose decreased laminin binding by 70% and neuraminidase treatment of laminin by 50%, while a recombinant B1 chain of laminin, containing high-mannose type oligosaccharides, inhibited binding by only 25%. This suggests that terminal sialic acids on laminin compete for a specific sugar binding protein(s) on H. pylori cells. PMID- 8364521 TI - Prevalence of IgA receptors in clinical isolates of Streptococcus pyogenes and Streptococcus agalactiae: serologic distinction between the receptors by blocking antibodies. AB - Group A and B streptococci (Streptococcus pyogenes and Streptococcus agalactiae) are the only known bacterial pathogens expressing IgA Fc-receptors. However, the IgA binding proteins of the two species have been found genetically unrelated. In the present investigation the binding of human IgA among clinical isolates of group A and group B streptococci was studied and the respective IgA-binding epitopes were compared serologically. Surface binding of radiolabelled, monoclonal human IgA1 occurred in 38% of 115 unselected group A streptococcal isolates. Comparing four predominant T-types, IgA-binding was found in 77% and 85%, respectively, of types T4 and T28 strains but only in 5% and 25%, respectively, of T1 and T12 strains. In group B streptococci, 70% of 58 type Ib strains but only 2% of 399 strains of other serotypes bound IgA. Using rabbit immune sera raised to the two streptococcal species it was found that strains exhibiting IgA Fc-receptors often induced antibodies blocking the binding of IgA to bacteria. Furthermore, the blocking shown by an individual serum was restricted to the streptococcal group used for immunization showing that also the IgA-binding eptiopes in group A and B streptococci are conformationally distinct. Though infections with serotypes often binding IgA, compared to other types, are not known to differ, it is assumed that the non-immune binding of IgA might favour mucosal colonization of the organisms. PMID- 8364522 TI - Antigenic diversity of IgA receptors in Streptococcus pyogenes. AB - In a previous study, group A and group B streptococcal IgA receptors were shown to differ serologically, in agreement with their known structural unrelatedness. The present study was undertaken to serologically compare the IgA binding epitopes of group A streptococcal strains representing various serotypes by the use of antisera to this species. It was found that blocking antibodies occurred in antisera to IgA binding but not to non-binding strains and that binding of IgA to a streptococcal strain was generally blocked by antiserum to the homologous type. However, cross-testing of a panel of 11 IgA binding strains, representing various M and T serotypes, with 10 different antisera to group A streptococci, demonstrated that IgA receptors were inhibited to a highly variable degree and that inhibition patterns were unique for each type. Comparing solubilized IgA receptors of various strains in immunoblot experiments, a variation in the molecular mass, between approximately 35 and 45 kDa, emerged. The IgA binding epitopes, analogous to protective sites of streptococcal M-protein, thus exhibited hypervariability which may suggest that IgA binding also plays a key role for evading host immune defence mechanisms. PMID- 8364523 TI - Application of flow cytometry to the study of antiphagocytic properties of Klebsiella pneumoniae capsular polysaccharide. AB - We used flow cytometry to compare the effects of whole cells and capsular polysaccharides of Klebsiella pneumoniae on the phagocytic ability ot polymorphonuclear leukocytes. Our results showed a light decrease in phagocytic activity in the presence of capsular polysaccharides, but a marked decrease with whole cells. Our findings suggest that the resistance to phagocytosis in these microorganisms is not due exclusively to their capsule, as claimed by other authors. PMID- 8364524 TI - Animal and human antibodies reactive with the outer surface protein A and B of Borrelia burgdorferi are borreliacidal, in vitro, in the presence of complement. AB - Polyspecific antibodies present in ascitic fluids of mice (pMIAFs) immunized with whole Borrelia burgdorferi cells exerted borreliacidal activity in vitro when tested with complement and homologous antigen but not with heterologous B. hermsii. Similarly, monospecific mouse antibodies obtained by immunizing mice with purified preparations of outer surface protein A and B of B. burgdorferi were borreliacidal. On the contrary, mouse monospecific antibodies raised against the 41-kDa flagellar protein of B. burgdorferi did not kill borreliae in the presence of complement. A complement-mediated, in vitro, borreliacidal activity was observed in human sera from patients with Lyme disease when antibodies against OspA and/or OspB were detectable in sera by the Western blotting technique. The in vitro borreliacidal activity of human sera was evident after 14 h incubation with live B. burgdorferi spirochaetes and complement, whereas antibodies present in mouse immune ascitic fluids killed borreliae after 1 h incubation. PMID- 8364525 TI - Analysis of intestinal flora of a patient with congenital absence of the portal vein. AB - A 14-year-old female patient, admitted for a closer examination of liver tumour (hepatocellular adenoma), was diagnosed as having a congenital absence of the portal vein. The blood ammonia level (approximately 120 micrograms dl-1) in the superior mesenteric vein was markedly low compared to the normal value of 300-350 micrograms dl-1 in the portal vein. The decreased ammonia concentration and urease activity of the patient's faeces were demonstrated. The dominant intestinal flora in the faeces of the patient, before operation, was Bifidobacterium sp., Bifidobacterium breve, Bifidobacterium lonqum, Lactobacillus plantarum, and after the operation Bacteroides vulgatus, Veillonella parvula, Peptococcus magnus Bifidobacterium longum. In contrast, Bifidobacterium bifidum, Bacteroides ureolyticus, Bacteroides ovatus and Bacteroides distasonis, B. ovatus, Bifidobacterium adolescentis were dominant flora in the faeces of two healthy volunteers, respectively. Among microorganisms isolated from the patient, Morganella morganii, Candida sp., Eubacterium aerofacience and Eubacterium rectale were strongly positive in urease activity in vitro; Streptococcus mitior, Staphylococcus intermedius, Micrococcus kristinae, Selenomonas ruminantum, Bacteroides ureolyticus and Lactobacillus casei ss. pseudoplantarum from the healthy volunteers. These results imply the homeostatic regulation system of faecal ammonia concentration by urease-producing microorganisms in the patient. PMID- 8364526 TI - Extracellular fibrinogenolytic enzyme of Aspergillus fumigatus: substrate dependent variations in the proteinase synthesis and characterization of the enzyme. AB - To get a better understanding of the role of the previously reported fibrinogenolytic enzyme of Aspergillus fumigatus, we investigated the in vitro conditions of enzyme synthesis and attempted to characterize it. Modification of the nitrogen source did not influence the extracellular serine-proteinase profile, but resulted in important quantitative differences in the yields in batch cultures. The enzyme synthesis appeared to be an inducible phenomenon in A. fumigatus since it was initiated exclusively in the presence of proteins or protein hydrolysate. Free amino acids or inorganic nitrogen compounds could not promote significant enzyme production. Moreover, peptone at a concentration of 0.1% appeared to be the best inducer of enzyme synthesis. Conversely, modification of the carbon source did not affect fungal growth or enzyme synthesis. However, the production of chymotrypsin was highly sensitive to the carbohydrate level in the culture medium and, with peptone as nitrogen source, highest yields were obtained in the presence of 0.3 or 0.5% glucose. Culture filtrates of A. fumigatus CBS 113.26 grown with peptone or nitrate as nitrogen source were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Comparison of the protein patterns suggested for the proteinase a molecular mass of 33 kDa which was confirmed by chromatographic purification of the enzyme through (N alpha-CBZ)-D-phenylalanine agarose. PMID- 8364527 TI - Feasibility of prophylaxis and therapy against gram-negative infections by human monoclonal antibodies. AB - In a murine model of Gram-negative sepsis, we have shown that the prophylactic application of human monoclonal antibodies (HmAbs) with specificity for lipopolysaccharides (LPS) of Pseudomonas aeruginosa protected against bacterial infection. In this paper we show that the therapeutical application of 5 micrograms of these HmAbs up to 6 h after challenge with a lethal dose of live P. aeruginosa results in a protection rate of 70-90%. Administration 18 h after bacterial challenge, diminished the protection to 43% survival rate. Furthermore, using a mixture of HmAbs recognizing a total of six different P. aeruginosa serotypes, no interference in their protective capacities was found. Finally, these HmAbs also protected galactosamine-sensitized mice against lethal challenge with LPS. Our data show that the described HmAbs confer bactericidal activity as well as anti-endotoxic activity in vivo. PMID- 8364528 TI - What eye fixations tell us about phonological recoding during reading. AB - Evidence for phonological recoding during reading has depended on paradigms requiring readers to make some response in addition to reading (e.g., proofreading, concurrent speaking). Our subjects simply read text for comprehension, and their eye movements were monitored for spontaneous disruptions when encountering homophonic errors (e.g., He wore blew jeans.) versus nonhomophonic errors (e.g., He wore blow jeans.). Eye fixation behaviour revealed that readers initially experienced as much difficulty when encountering a homophonic error as a nonhomophonic one; however homophony facilitated the recovery process, at least for homophones that shared the same length as their context correct mates (e.g., blew/blue but not war/wore). The results support a theory of lexical access in which phonological sources of activation and influence are delayed relative to orthographic sources, rather than a theory in which phonological codes predominate. PMID- 8364529 TI - The use of information below fixation in reading and in visual search. AB - Two experiments examined whether or not readers obtain useful information from below the currently fixated line. In Experiment 1, subjects read passages of text and the availability of visual information below the line fixated was manipulated using a variant of the moving window technique. Reading was no slower when there was no letter information below the fixated line than when there was full information below the fixated line. However, a condition which made the strings of letters below the fixated line less "wordlike" caused reading to be slowed down by about 6% relative to the other conditions. In Experiment 2, subjects searched for a target word through passages of text. Subjects occasionally detected targets below the line they were fixating; however, there was no clear evidence that the availability of information below the line made search more efficient. It thus appears that in reading (or in other tasks where words are being identified and the eyes move horizontally along a line of text), little visual information is extracted below the line of text fixated. PMID- 8364530 TI - Eye movement control during reading: fixation measures reflect foveal but not parafoveal processing difficulty. AB - The main purpose of this study was to determine whether, during natural reading, the difficulty of the upcoming parafoveal word affects eye movement behaviour on the currently fixated word. A model in which visual attention is allocated in parallel over both the fixated and the upcoming parafoveal word predicts such as effect, while a sequential attention allocation model in which attention is directed first to the fixated word and then to the upcoming parafoveal word, does not. The data reported here show that neither the frequency nor the combined length, frequency and class of the upcoming word affect eye movement behaviour on the current word. These data support the sequential attention--parallel programming model of eye movement control in reading. PMID- 8364531 TI - Thematic roles in sentence parsing. AB - Two eyetracking experiments examined the reading of sentences like "While the police/truck stopped the Datsun disappeared into the night." A paper by L. Stowe (Thematic structures and sentence comprehension. In G. N. Carlson and M. K. Tanenhaus (Eds.), Linguistic structure in language processing, 1989) indicated that an inanimate subject ("truck" in "After the truck stopped the Datsun disappeared ...") is taken as theme of the ergative verb ("stop"), preventing the assignment of the postverbal noun phrase ("the Datsun") as direct object. This eliminates the disruption of reading that is normally observed on the disambiguating verb ("disappear"). The present experiments found the pattern of results reported by Stowe when looking at the disambiguating region of a sentence. However, the results for earlier regions suggest that the postverbal noun phrase was initially taken as direct object of an ergative verb even when the subject was inanimate. It appears that the inanimacy of the subject may not have guided the initial syntactic analysis, but rather facilitated the revision of an initial misanalysis. PMID- 8364532 TI - Context effects in syntactic ambiguity resolution: discourse and semantic influences in parsing reduced relative clauses. AB - This article examines how certain types of semantic and discourse context affect the processing of relative clauses which are temporarily ambiguous between a relative clause and a main clause (e.g., "The actress selected by the director ..."). We review recent results investigating local semantic context and temporal context, and we present some new data investigating referential contexts. The set of studies demonstrate that, contrary to many recent claims in the literature, all of these types of context can have early effects on syntactic, ambiguity resolution during on-line reading comprehension. These results are discussed within a "constraint-based" framework for ambiguity resolution in which effects of context are determined by the strength and relevance of the contextual constraint and by the availability of the syntactic alternatives. PMID- 8364533 TI - The intensity dimension of thought: pupillometric indices of sentence processing. AB - This article explores the intensity of processing during sentence comprehension by measuring pupillary response during reading. Two experiments contrast the processing of simpler versus more complex sentences. The two more complex sentence types, object-relative center-embedded sentences and filler-gap sentences, not only take longer to process than their simpler counterparts, but they also produce a larger change in pupil diameter. We propose that the pupillary response is an indicator of how intensely the processing system is operating. The more complex sentences evoke some intense processing at the point in the sentence where a syntactic complexity is first encountered. The gaze durations at these points are elevated, indicating the immediate response to the demand of the syntactic processing. The pupil then starts to dilate, reaching a maximal diameter approximately 1.3 s later. The results from these various performance measures are integrated within a resource-limited computational model of comprehension. The paper develops a model of comprehension that includes an intensity dimension of thought, drawing a correspondence between the computational model's consumption of resources and the human pupillary response. PMID- 8364534 TI - Writing quality, reading skills, and domain knowledge as factors in text comprehension. AB - Subjects listened to and recalled three passages. Each subject was also given a general reading comprehension test. The passages were presented either in such a way that subjects could use their general knowledge to help understand them, or in such a way that no specific world knowledge seemed applicable. This was achieved by giving the passages a helpful title, versus no title or an unhelpful title. The passages were written in two different versions, preserving their content but varying their style. In one version, the language was as helpful as we could make it in signalling to the listener discourse importance, while in the other version the language was as unhelpful as we could make it while still writing an English text. All three factors--domain knowledge, writing style, and skill--significantly affected reproductive recall, and there were no interactions between these factors. However, while good writing was sufficient to improve the reproduction of the texts, an analysis of the recall elaborations subjects made revealed that the correctness of their elaborations depended strongly on the availability of appropriate domain knowledge. Thus, good writing and domain knowledge are not simply substitutable, but affect comprehension in somewhat different ways. PMID- 8364535 TI - Effects of sentence form on the construction of mental plans from procedural discourse. AB - Memory for procedural discourse was examined in two experiments. In Experiment 1, memory was assessed using recall; in Experiment 2, a recognition test was used. In both experiments, the memorability of three types of action statements were compared: a transitive verb form, in which the action was described by a main clause; a verbal adjective form, in which the action was indicated by an adjective derived from a verb; and an implicit action form, in which the action was only implied. Information associated with transitive verbs and verbal adjectives was more likely to be recalled than information associated with implicit actions. Although a manipulation of prior knowledge affected overall recall performance, it did not interact with sentence form. In addition, recognition accuracy was affected by neither sentence form nor prior knowledge. To account for these results, it was proposed that transitive verbs and verbal adjectives generate a semantic representation that includes features of the action, whereas implicit actions do not. This difference in semantic representation leads to structural differences in a mental plan for the task. The obtained effects on recall reflect these differences in plan structure. PMID- 8364536 TI - Characterization of a human alpha 1-antitrypsin null allele involving aberrant mRNA splicing. AB - alpha 1-Antitrypsin (alpha 1AT) is a major protease inhibitor present in high concentrations in the plasma. Inheritance of alpha 1AT deficiency or null alleles (alleles associated with no detectable serum alpha 1AT) is associated with an increased risk for emphysema. In contrast to beta zero-thalassemia variants in which RNA splicing and promoter mutations constitute more than 40% of beta zero thalassemia variants, all nine alpha 1AT null variants identified are the result of mutations involving the protein coding region of the alpha 1AT gene. During routine screening of individuals applying for enrollment in the USA alpha 1AT Deficiency Registry we identified an individual with emphysema and a Protease Inhibitor (PI*) type heterozygous for a novel alpha 1AT null allele. Direct DNA sequencing of this individual's alpha 1AT alleles demonstrated one normal and one novel allele, designated PI*QOwest, characterized by a single G-->T base substitution at position 1 of intron II, a highly conserved nucleotide position in vertebrate splice donor sites. Metabolic labeling of NIH-3T3 cells transfected with a plasmid vector containing an alpha 1AT minigene with the QOwest mutation demonstrated an absence of detectable immunoprecipitable alpha 1AT confirming that the G-->T mutation is responsible for the observed null phenotype. QOwest alpha 1AT minigene transfected cells expressed 25-100 fold less alpha 1AT mRNA than a normal control. DNA sequencing of polymerase chain reaction amplified mRNA obtained from transfected cells demonstrated the use of a cryptic splice site 84 bases upstream from the normal splice site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364537 TI - Haplotype analysis to determine the position of a mutation among closely linked DNA markers. AB - Positional cloning involves first finding linkage between an inherited phenotype (such as a disease) and a DNA marker, followed by the use of a variety of physical and genetic mapping techniques to move from linkage to mutation. If there is a founder effect within a population, crossovers are often rare between the mutation causing the phenotype and closely situated markers and increasing disequilibrium may be observed as the site of the mutation is approached. Standard coefficients of disequilibrium may, however, be insensitive to the relative position of close markers and the mutation, because they depend upon allele frequencies in the normal population compared to those of the founder chromosome. Using cystic fibrosis in European populations as a model system, alternative methods for determining the position of a mutation are discussed. These include haplotype parsimony and three-way interval likelihood analysis. Both methods predict the location of the major CF mutation accurately from a real set of more than 600 European CF chromosomes. PMID- 8364538 TI - Variation of short tandem repeats within and between populations. AB - Using the polymerase chain reaction (PCR) the frequency distributions of three short tandem repeats (STR) were investigated in five populations: North European, Cypriot, Pakistani, Gujarati and Vietnamese. Each STR is situated within an intron; the markers are in the genes for human coagulation factor XIII (4bp repeat), lipoprotein lipase (4bp repeat) and CD4 (5bp repeat). Population data were generated for each STR and allele frequencies calculated. A calculation of the level of population substructuring for the three systems was also made. The lipoprotein lipase STR data showed no evidence for population substructuring, but there was a significant level of substructuring in the other two systems. This initial pilot study demonstrates the need to validate each marker used for DNA profiling in different human populations, and that some markers (such as LPL) can be used with confidence in widely differing ethnic groups, while others (such as CD4 and F13A) may be of value in distinguishing sub-groups. PMID- 8364539 TI - Functional complementation in mouse-human radiation hybrids assigns the putative murine scid gene to the pericentric region of human chromosome 8. AB - Fragments of human chromosome 8 were introduced into cells derived from murine scid mice via X-irradiation and somatic cell fusion. The resulting hybrid clones contained human DNA fragment(s) which complemented the hyper-radiosensitivity of the scid cells. Alu-PCR products from these hybrids were used for chromosome painting using the technique of chromosome in situ suppression hybridization, allowing assignment of the human HYRC (hyper-radiosensitivity of murine scid mutation, complementing) gene, a candidate for a V(D)J recombinase gene, to human chromosome 8q11. PMID- 8364540 TI - A physical map of the C6 and C7 complement component gene region on chromosome 5p13. PMID- 8364541 TI - Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene fails to identify new mutations in Swedish Alzheimer's disease patients. PMID- 8364542 TI - A dinucleotide deletion (-delta GA115) in the tyrosinase gene responsible for type I-A (tyrosinase negative) oculocutaneous albinism in a Pakistani individual. PMID- 8364543 TI - A 4 basepair deletion in exon 4 of the human lipoprotein lipase gene results in type I hyperlipoproteinemia. PMID- 8364544 TI - A missense mutation (178Cys-->Tyr) and two neutral dimorphisms (115His and 333Ser) in the human coagulation factor VII gene. PMID- 8364545 TI - A new disease-causing mutation in the GAP-related domain of the NF1 gene. PMID- 8364547 TI - An 8-bp deletion in exon B of the iduronate-2-sulphate sulphatase gene in a case of Hunter disease. PMID- 8364546 TI - A novel missense mutation in the phenylalanine hydroxylase gene of a homozygous Pakistani patient with non-PKU hyperphenylalaninemia. PMID- 8364548 TI - Human erythropoietic protoporphyria: identification of a mutation at the splice donor site of intron 7 causing exon 7 skipping of the ferrochelatase gene. PMID- 8364549 TI - A new mutation causing inherited growth hormone deficiency: a compound heterozygote of a 6.7 kb deletion and a two base deletion in the third exon of the GH-1 gene. PMID- 8364550 TI - A new mutation of exon 5 of the P53 gene in breast cancer. PMID- 8364551 TI - Dinucleotide repeat polymorphisms at the D4S126 and D4S114 loci. PMID- 8364552 TI - Dinucleotide repeat polymorphism at the DXS1146 locus. PMID- 8364554 TI - The detection of a VNTR at the Huntington disease genetic marker D4S10. PMID- 8364553 TI - A TaqI site identifies the *A allele at the ACP1 locus. PMID- 8364555 TI - Tetranucleotide repeat polymorphism at D17S846 maps within 40 kb of GAS at 17q12 q22. PMID- 8364557 TI - Dinucleotide repeat polymorphism at the D11S982E locus. PMID- 8364556 TI - Dinucleotide repeat polymorphism at the human recoverin RCVI gene locus on chromosome 17p. PMID- 8364558 TI - Dinucleotide repeat polymorphism at the locus D13S231. PMID- 8364559 TI - A compound nucleotide repeat in the neurofibromatosis (NF1) gene. PMID- 8364560 TI - A microsatellite polymorphism at the THRB locus. PMID- 8364561 TI - A dinucleotide repeat polymorphism in the human LAMB2 gene on chromosome 1q. PMID- 8364562 TI - Dinucleotide repeat polymorphism at the D6S348 locus. PMID- 8364563 TI - Two consecutive dinucleotide repeats constitute an informative marker at the alpha 1-antichymotrypsin (AACT) locus. PMID- 8364564 TI - A CA dinucleotide polymorphism at D17S107 (17q12-q24). PMID- 8364565 TI - Length polymorphism within a complex dinucleotide repeat in the human decorin (DCN) gene. PMID- 8364566 TI - Tetranucleotide repeat polymorphism at the D8S344 locus. PMID- 8364567 TI - New human DNA polymorphisms submitted to the genome data base. PMID- 8364568 TI - Autosomal dominant supravalvular aortic stenosis: localization to chromosome 7. AB - Supravalvular aortic stenosis (SVAS) is a localized or diffuse congenital narrowing of the ascending aorta which may occur sporadically, as a familial defect, or in association with Williams syndrome. Familial cases suggest an autosomal dominant gene defect but the underlying molecular basis of SVAS is unknown. In this study, we sought to localize the genetic defect in familial SVAS by linkage analysis in a large three generation family. A total of 44 polymorphic markers were examined for linkage, including 17 Southern blot-based RFLPs, 2 PCR based RFLPs, and 25 microsatellites, primarily of the (CA)n repeat type. We report linkage of the disease phenotype to a highly informative (CA)n repeat marker, Mfd 50, at locus D7S440 which has been localized to chromosome arm 7q. Using a 100% penetrance model, which was more conservative than lower values of penetrance, a peak LOD score of 4.66 at a recombination frequency of 0.043 was found. A number of candidate genes have been localized to this region, including collagen 1A2, laminin B1, and elastin. Based on our preliminary linkage data, the abnormal microscopic appearance of aortic elastic fibers in SVAS, and analogous animal and human diseases associated with elastic fiber and vascular abnormalities, there is indirect evidence suggesting elastin as a possible candidate gene for this disorder. PMID- 8364569 TI - Exclusion of the involvement of all known retinitis pigmentosa loci in the disease present in a family of Irish origin provides evidence for a sixth autosomal dominant locus (RP8). AB - Retinitis Pigmentosa (RP) is the most prevalent degenerative retinal disease of mendelian origin, currently affecting approximately 1.5 million people worldwide. To date it has been established that a minimum of five different genes maybe involved in the pathogenesis of autosomal dominant forms of RP (adRP). The genes encoding two retinal specific proteins, rhodopsin and peripherin/RDS, have been implicated in causing adRP due to the observation of many different mutations in these genes in patients suffering from RP. The three remaining adRP genes have been mapped to specific regions of human chromosomes but as yet are uncharacterized. We have investigated if there is evidence for the presence of another locus in the genome which when mutated causes adRP. We have utilised polymorphic genetic markers which have previously been mapped to each of the regions known to harbour adRP genes, to test for the exclusion or linkage of the disease gene segregating in a pedigree of Irish origin and find no evidence for linkage. Hence we provide definitive evidence for the involvement of yet another locus. The implications of high levels of genetic heterogeneity inherent in adRP are discussed in relation to diagnosis, prognosis and future therapies. PMID- 8364570 TI - Mapping the Von Hippel-Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis. AB - Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome in which affected individuals have a greatly increased predisposition to the development of haemangioblastomas of the central nervous system and retina, renal cell carcinoma and phaeochromocytoma. The VHL gene has been mapped to chromosome 3p25-p26 by genetic linkage studies and we have previously demonstrated that the VHL gene is tightly linked to the D3S601 locus (Zmax = 18.86 at theta = 0.0) suggesting that D3S601 maps close to the VHL disease gene. We have constructed a long range physical map around D3S601 and screened 91 VHL patients from 80 kindreds for germline rearrangements using pulsed field gel electrophoresis. Two patients showed abnormal fragments in Mlul digested DNA probed with D3S601. Further analysis was consistent with both patients having germline deletions (approximately 120 kb and 50 kb) telomeric to D3S601. These results have (i) established the position of the VHL disease gene with respect to D3S601, (ii) refined the localisation of the VHL disease gene to a small region (approximately 50 kb) of chromosome 3p25-p26 and (iii) excluded the plasma membrane Ca(+)+-transporting ATPase isoform 2 (PMCA-2) gene as a candidate gene for VHL disease. PMID- 8364571 TI - Mapping of the distal boundary of the X-inactivation center in a rearranged X chromosome from a female expressing XIST. AB - A female patient with primary amenorrhea, immature secondary sexual characteristics, and tall stature was found to have a normal X chromosome and a rearranged X [rea(X)] chromosome that resembled an 'isochromosome' Xp, but retained the proximal portion of Xq. The rea(X) was interpreted as rec(X)dup p,inv(X)(p11.4q13). Replication studies demonstrated that the rea(X) was always the late-replicating and, therefore, presumably inactive X chromosome, which must contain the X-inactivation center. Consistent with this interpretation, fluorescence in situ hybridization demonstrated that the rea(X) retained the XIST gene, and reverse transcription polymerase chain reaction analysis showed that XIST was expressed in the patient's cells. By fluorescence in situ hybridization with previously mapped probes, the breakpoint of the rea(X) was located within an approximately 500-kb region located approximately 200 to 700 kb distal to the XIST locus. This is the closest breakpoint distal to XIST in an inactivated X chromosome and, therefore, defines a new distal boundary for the X-inactivation center in humans. PMID- 8364572 TI - Construction of cosmid contigs and high-resolution restriction mapping of the Huntington disease region of human chromosome 4. AB - The gene responsible for Huntington disease (HD) has been localized to a 2.2 million base pair (Mbp) region between the loci D4S10 and D4S98 on the short arm of human chromosome 4. As part of a strategy originally designed to clone the gene based on its chromosomal location, we and others previously identified overlapping yeast artificial chromosome (YAC) clones covering most of this region. While these YAC clones were useful for initially obtaining long-range clone continuity, a number of features of the YACs indicated that smaller clones are generally more useful in the subsequent steps of the positional cloning strategy. In this paper, we use these YAC clones to generate sets of overlapping cosmid clones covering most of the HD region. We isolated a large number of cosmids by screening a chromosome 4-specific cosmid library with labeled DNA from a minimal overlapping set of YAC clones. These cosmid clones were further analyzed by restriction mapping and hybridization experiments, leading to the assembly of 185 cosmids into eleven contigs covering more than 1.65 Mbp and to a fine-structure restriction map of the region. Nine of these contigs cover 90 percent of the 1.7 Mbp subregion between loci D4S125 and D4S98 where the HD gene is now known to lie. The detailed restriction map and the cosmid clones should facilitate the identification and localization of cDNAs and polymorphic markers, and they provide reagents for large scale DNA sequencing of this region of the human genome. Our results suggest that this strategy should be generally useful for converting YAC clones into cosmid contigs and generating high-resolution restriction maps of genomic regions of interest. PMID- 8364573 TI - A microsatellite-based index map of human chromosome 11. AB - We have constructed a continuous index map of 25 microsatellite markers on human chromosome 11. The markers have been typed in 40 CEPH families, have heterozygosities of 69% or higher and can be typed by PCR. The odds against inversion of adjacent marker loci order are at least 10(5):1. The sex average map covers a total of 162 cM with no gap exceeding 15 cM. Total lengths for female and male maps are 205 and 123 cM, respectively. By use of a hybrid cell panel or by in situ hybridization, 16 of the markers have also been mapped cytogenetically, providing a good correlation of the index map with the cytogenetic map. The map will facilitate high resolution mapping of additional polymorphic loci and of disease genes on chromosome 11. PMID- 8364575 TI - Cloning of the breakpoints of a submicroscopic deletion in an Angelman syndrome patient. AB - The majority of cases of the two distinct disorders Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from cytogenetic deletions of chromosome 15q11 q13. These deletions are exclusively of maternal origin in AS but of paternal origin in PWS indicating that the 15q11-q13 region is subject to genomic imprinting. Transmission of a submicroscopic deletion in one three generation family resulted in AS only upon maternal transmission of the deletion with no clinical phenotype associated with paternal transmission (1,2). The breakpoint of this submicroscopic deletion has been cloned and sequenced. This is the first deletion junction from the AS/PWS region which has been so characterized. The nucleotide sequence of the deletion junction revealed a 19 bp insertion of unknown origin with no evidence of repetitive elements. A probe from the proximal deletion breakpoint, PB11, lies within the currently defined minimum region of deletion overlap in PWS, which contains the SNRPN and D15S63 loci. Our results suggest that the imprinted gene(s) responsible for the PWS phenotype are proximal of pB11 in this deletion overlap region. PMID- 8364574 TI - PAX6 mutations in aniridia. AB - Aniridia is a congenital malformation of the eye, chiefly characterised by iris hypoplasia, which can cause blindness. The PAX6 gene was isolated as a candidate aniridia gene by positional cloning from the smallest region of overlap of aniridia-associated deletions. Subsequently PAX6 intragenic mutations were demonstrated in Smalleye, a mouse mutant which is an animal model for aniridia, and six human aniridia patients. In this paper we describe four additional PAX6 point mutations in aniridia patients, both sporadic and familial. These mutations highlight regions of the gene which are essential for normal PAX6 function. In addition, the frequency at which we have found PAX6 mutations suggests that lesions in PAX6 will account for most cases of aniridia. PMID- 8364576 TI - Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity. AB - Hereditary tyrosinemia type 1 is an autosomal recessive disease caused by a deficiency of the last enzyme in the catabolic pathway of tyrosine, fumarylacetoacetate hydrolase (FAH). To analyze the mutations involved in this disease, and as a first step towards elucidating the mechanisms regulating the transcription of the FAH gene, we have isolated and characterized the human gene coding for FAH. The gene contains 14 exons and spans approximately 35 kilobases of DNA. The 5' end of the gene is highly GC-rich, and eleven putative binding sites for the transcription factor Sp 1 were identified in the proximal region of the promoter. We investigated the molecular basis of FAH deficiency in a hereditary tyrosinemia type 1 patient whose liver FAH showed a very low enzymatic activity. Sequencing of the liver FAH cDNA of the patient revealed a C to A transversion in the FAH mRNA, which predicted the replacement of an alanine (A) residue with an aspartic acid (D) residue at position 134 (A134D) of the amino acid sequence of the corresponding protein. Direct sequencing of genomic DNA indicated that the patient was heterozygous for the A134D mutation. The allele that does not carry the A134D mutation was expressed at a very low level in the liver of the patient. Expression of the mutant allele in CV-1 cells confirmed that the A134D mutation was responsible for the lack of enzymatic activity in the liver of the patient. PMID- 8364577 TI - The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions. AB - We have used cell lines from patients with deletions and translocations involving the Xp22 region to map the genes for two X-linked disorders, ocular albinism type 1 (OA1) and microphthalmia with linear skin defects (MLS). Using existing and newly isolated DNA markers, the map position within Xp22 of key patient breakpoints, defining the boundaries of the genomic regions involved in these disorders (the critical regions), has been precisely determined. A 2.6 Mb yeast artificial chromosome (YAC) contig, spanning the critical regions for these two disorders, was assembled. Detailed long-range restriction analysis of the contig established the sizes of the critical regions to be 200 kb for OA1 and 800 - 925 kb for MLS. Ten potential CpG-islands, representing candidate sites for genes, have been mapped within the 2.6 Mb region. Our data should greatly facilitate efforts aimed at cloning the genes for these developmental defects. PMID- 8364578 TI - Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. AB - Marfan syndrome results from mutations in an extracellular matrix glycoprotein, fibrillin. Previous studies have characterized approximately 6.9-kb of the estimated 10-kb fibrillin transcript. We have now completed the primary structure of fibrillin, elucidated the exon/intron organization of the gene and derived a physical map of the genetic locus. Pre-fibrillin consists of 2,871 amino acids which, excluding the signal peptide, are arranged into five structurally distinct regions. The largest of these regions comprises about 75% of the entire protein and consists of numerous repeated cysteine-rich sequences homologous to the peptide motifs of the epidermal growth factor (EGF) and transforming growth factor-beta binding protein (TGF-bp). Forty-three of the forty-six EGF-like repeats contain a calcium binding consensus sequence (EGF-CB) conceivably mediating protein-protein interactions. Fibrillin exhibits a few additional cysteine-rich modules that are apparently unique to this macromolecule and may represent evolutionary variants of the EGF-CB and TGF-bp motifs. Almost all of the cysteine-rich repeats are encoded by single exons; consequently, the fibrillin gene is relatively large (approximately 110-kb) and highly fragmented (65 exons). This study provides the first comprehensive analysis of the fibrillin gene and relevant information for the full characterization of Marfan syndrome mutations. PMID- 8364579 TI - Paired STSs amplified from radiation hybrids, and from associated YACs, identify highly polymorphic loci flanking the ataxia telangiectasia locus on chromosome 11q22-23. AB - The high resolution mapping of the ataxia telangiectasia (A-T) locus on chromosome 11q22-23 requires the generation of new polymorphic markers specifically within the segment of 11q22-23 to which the locus has been assigned. We have made use of a library of Alu-PCR clones, amplified from a radiation reduced somatic cell hybrid containing the relevant chromosome 11 segment, to generate sequence tagged sites (STS) within the 11q22-23 region and have used YAC clones to extend the loci identified by these STSs. The identification of paired polymorphisms (from Alu-PCR and the associated YAC derived clone), which are physically linked, but which show minimal linkage disequilibrium, provides a highly informative haplotype for use in genetic linkage analysis in A-T families. We describe the characterisation of 2 such polymorphic loci, D11S535 and D11S611, which map between existing flanking markers, and which provide additional information on the location of the major A-T locus. PMID- 8364580 TI - Identification of germline mutations in the RB1 gene by denaturant gradient gel electrophoresis and polymerase chain reaction direct sequencing. AB - Germline mutations in the RB1 gene confer hereditary predisposition to retinoblastoma. The majority of these mutations occur de novo and differ from one patient to another. Cytogenetics and Southern blotting were shown to detect less than 15% of constitutional rearrangements. In this study we used the polymerase chain reaction (PCR) combined with denaturant gradient gel electrophoresis (DGGE) to detect point mutations or small deletions and insertions in a pool of 120 unrelated retinoblastoma patients. Partial DGGE analysis of the RB1 gene enabled us to identify sequence alterations generating stop codons, leading to amino acid substitution or affecting splice sites as well as several polymorphisms. Most of the nucleotide changes detected are flanked by direct repeats. The approach described here has proved to be a useful method for the detection of germline mutations in the RB1 gene. PMID- 8364581 TI - Molecular analysis of British facioscapulohumeral dystrophy families for 4q DNA rearrangements. AB - Facioscapulohumeral muscular dystrophy is an important autosomal dominant neuromuscular disorder that has been localised to 4q35. We have analysed our extensive panel of 45 families with a new DNA marker p13E-11. The findings, based on multiply informative individual meioses and multipoint mapping, suggest that probe p13E-11 is the closest marker for the disorder and it is likely to be located proximal to the disease locus as are all the other present markers. In nine of the ten new mutations studied, a new smaller EcoRI fragment which was not present in either of the parents was detected, indicating that a de novo DNA rearrangement is indeed associated with the development of the disease state. However, in view of the difficulty in defining the size of over 30kb alleles and the recombinant events observed with p13E-11, we suggest that it should be used in combination with another VNTR marker until a close distal flanking marker for this condition is identified or the gene itself is isolated. PMID- 8364582 TI - An alternatively-spliced mRNA in the carboxy terminus of the neurofibromatosis type 1 (NF1) gene is expressed in muscle. AB - The gene for neurofibromatosis type 1 (NF1) was identified by positional cloning and found to contain two alternatively spliced exons. The first described alternatively spliced exon (exon 23a) is located within the GAP-related domain of the gene and inserts an additional 63 nucleotides into the NF1 mRNA. The second alternatively spliced exon (exon 48a) is located near the extreme carboxy terminus of the gene and inserts an additional 54 nucleotides into the mRNA. This second isoform, termed 3'ALT, was originally detected while screening a fetal brain cDNA library. Examination of its expression by reverse-transcribed RNA PCR demonstrates high level of expression in cardiac muscle, skeletal muscle and smooth muscle. Trace levels of expression are detected in brain and nerve. The 3'ALT isoform is expressed in fetal cardiac muscle, adult left ventricle and cardiac Purkinje cells. Further confirmation of the existence of this isoform was obtained by blotting the PCR products with a radiolabeled oligonucleotide entirely derived from sequences contained within exon 48a and by direct sequencing of the PCR products. Additionally, this isoform is expressed in muscle tissues from other vertebrate species. The expression of this isoform in muscle suggests that the NF1 gene may play additional tissue-specific roles in muscle development and signal transduction. PMID- 8364583 TI - The state of DNA methylation in the promoter and exon 1 regions of the human gene for the interleukin-2 receptor alpha chain (IL-2R alpha) in various cell types. AB - The gene for the human interleukin-2 receptor alpha chain (IL-2R alpha) is expressed only in stimulated, not in resting, human T lymphocytes. This gene, in conjunction with others, plays a pivotal role in eliciting the T cell-mediated immune response. We have investigated the promoter and exon 1 region, the nucleotide -300 to +300 region of this gene relative to the position of transcriptional initiation at nucleotide +1, particularly with respect to the extent of DNA methylation at the 5'-CG-3' sequences and its changes upon induction. By using RNA transfer analyses and the in vivo footprinting technique, we have confirmed the previously reported finding that, upon stimulation of lymphocytes by phytohemagglutinin (PHA) plus interleukin-2 (IL-2), the IL-2R alpha gene can be induced to be transcribed. The region of the IL-2R alpha gene analyzed for 5'-CG-3' methylation by the genomic sequencing method or a polymerase chain reaction-based method subsequent to HpaII or HhaI cleavage of the DNA does not seem to be significantly methylated in most cell types tested, except for the cytidine residue in position +198 which is partly methylated. In the DNA of cells from a chronic B cell lymphatic leukemia 5'-CCGG-3' sequences in the exon 1 region are almost completely unmethylated. These results suggest that the promoter of a gene that is crucial in promoting the immune response and may have to be activated momentarily, will not be silenced by a long-term mechanism like DNA methylation. It is striking that the absence of DNA methylation in this promoter and exon 1 segment also extends to cell types not directly associated with the immune response and even to continuous cell lines. PMID- 8364584 TI - Variants of glucose-6-phosphate dehydrogenase are due to missense mutations spread throughout the coding region of the gene. AB - Glucose-6-phosphate dehydrogenase (G6PD) is remarkable for its genetic diversity in humans. Many variants of G6PD have been described with wide ranging levels of enzyme activity and associated clinical symptoms. Fifty-eight different mutations have now been identified and these account for 97 named G6PD variants. The mutations are almost exclusively missense mutations, causing single amino acid substitutions. They are spread throughout the coding region of the gene, although there appears to be a cluster of mutations that cause a more severe clinical phenotype towards the 3' end of the gene. The absence of large deletions, frameshift mutations and nonsense mutations is consistent with the notion that a total lack of G6PD activity would be lethal. PMID- 8364585 TI - Mutations and polymorphisms in the prion protein gene. AB - Inherited forms of prion diseases are associated with mutations in the prion protein gene. A common polymorphism at codon 129 is also implicated in the predisposition of individuals to sporadic or iatrogenic forms of the disease. This update lists all the currently published mutations and polymorphisms together with their clinical phenotypes, and discusses the significance of the codon 129 genotype in inherited, sporadic, and iatrogenic cases. There are two categories of mutation. Insertions of additional numbers of an octapeptide lying within an octapeptide repeat region now account for six variations and there are also six point mutations. The identification of mutations in this gene has lead to a broadening of the spectrum of clinical phenotypes that can be classified as prion diseases and have provided an important tool in the diagnosis of familial dementias. PMID- 8364586 TI - Mutations and polymorphisms in the human ornithine transcarbamylase gene. AB - Deletions of variable size involving one or more exons, 29 different missense, nonsense, or frameshift mutations, and three polymorphisms have been found in patients with ornithine transcarbamylase (OTC) deficiency. Most of the deletions and mutations were found in patients with severe disease manifested clinically as acute neonatal hyperammonemia. A small number of mutations or somatic mosaicism for deletions were found in males with "late onset" disease and heterozygous females who were symptomatic. Approximately 10-15% of all molecular alterations associated with OTC deficiency are large deletions involving all or part of the OTC gene with or without contiguous genes on the short arm of the X chromosome. Approximately 10% of all point mutations involve the CpG dinucleotide of codon 141 with a CGA-->CAA transition producing a deleterious Arg-->Gln substitution in position 109 of the mature enzyme and causing the elimination of a TaqI recognition site. The majority of the remaining mutations in the OTC gene are unique to the affected family and are usually not found in unrelated patients. To date, two mutations have been described in the sequence of the "leader" peptide, 23 mutations have been found in the coding sequence of the "mature" enzyme, and four mutations have been discovered in splicing recognition sites. Approximately 20 single base polymorphisms have been postulated to exist by comparing two reported OTC gene sequences; six of these substitutions cause amino acid changes of which three have been confirmed in patients. Of the known point mutations, 27 are single base substitutions: 17 missense, 6 nonsense, 4 splice site, and the remaining 2 are single base deletions. PMID- 8364587 TI - Exon 44 nonsense mutation in two-Duchenne muscular dystrophy brothers detected by heteroduplex analysis. AB - Utilizing a heteroduplex method, we screened the dystrophin exon 43-45 region for point mutations, including small deletions and insertions. The method depends upon the formation of a heteroduplex between wild-type and mutant DNA PCR products. DNA specimens from one hundred and four DMD patients without detected deletions or duplications were multiplexed amplified for exons 43, 44, and 45. The PCR products were mixed with the PCR products from nonaffected controls, electrophoresed, and examined for the presence of altered mobility heteroduplex bands. An exon 44 nonsense mutation in two DMD brothers and a common intron 44 polymorphism were identified using this approach. Although the exon 44-45 region is a hotspot for deletion breakpoints, it does not appear to be prone to point mutations. The technique is extremely useful for screening several exons simultaneously and it allowed us to screen a large number of patients. PMID- 8364588 TI - Paternal mosaicism for a COL1A1 dominant mutation (alpha 1 Ser-415) causes recurrent osteogenesis imperfecta. AB - We describe a dominant point mutation in the COL1A1 gene causing extremely severe osteogenesis imperfecta (OI type II/III) which was detected in the dermal fibroblasts of a proband, diagnosed by ultrasonography at 24 weeks of gestation. Type I collagen secretion was reduced and pro alpha 1(I) chains were overmodified. The mutation was localised in one COL1A1 allele by chemical cleavage of mismatched bases in normal cDNA/proband's mRNA heteroduplexes, and identified by cloning and sequencing. A G-to-A transition which causes the substitution of Gly-415 with serine in the alpha 1(I) triple helical domain was found. The same mutation was detected in the father's spermatozoa and lymphocytes. Mosaicism in the father's germline explains the occurrence in the family of two additional OI pregnancies, which were documented by X-ray and ultrasound investigations. PMID- 8364589 TI - A leucine to arginine amino acid substitution at codon 46 of rhodopsin is responsible for a severe form of autosomal dominant retinitis pigmentosa. AB - To evaluate the extent to which rhodopsin mutations are involved in autosomal dominant forms of retinitis pigmentosa (adRP) we collected DNAs from patients with adRP and screened the rhodopsin coding sequence with single-strand conformational polymorphism (SSCP) analysis and DNA sequencing. This screening revealed a thymidine to guanine transversion at nucleotide 431 (nucleotide sequence numbers as per Genebank) in affected members of one family (RFS04). The nucleotide substitution leads to a missense mutation at the 46th amino acid of rhodopsin. The mutation occurs at an amino acid conserved in mammals and changes the hydrophobic nature of the protein at a transmembrane-spanning region. The mutation causes the substitution of a non-polar hydrophobic amino acid, leucine, for the basic amino acid arginine (Leu46Arg). This nucleotide substitution is unique to the family studied and occurs in the affected individuals in the family. Full-field electroretinograms (ERGs) in four affected members of the family showed nondetectable rod responses at an early age, with markedly reduced cone responses, and a faster than average rate of progression of the phenotype as measured by yearly ERGs. PMID- 8364590 TI - Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha 1-antitrypsin deficiency variant Pduarte. AB - alpha 1-Antitrypsin (alpha 1AT) is one of the most polymorphic gene loci in the human genome. alpha 1AT variants are typically identified by their migration position in an isoelectric focusing gel at pH 4-5. Heterogeneity of the isoelectric point of alpha 1AT variants, hence variant migration, most often results from amino acid substitutions which alter the net charge of the molecule. We identified an individual heterozygous for an alpha 1AT variant migrating in the "P" variant region which differs from other known "P" variants. Using isoelectric focusing on an immobilized pH gradient at pH 4.50-4.85 the novel P allele, Pduarte, migrates between Pst. albans and Plowell. Densitometric analysis of normal "M" type alpha 1AT and the deficiency variant Plowell major bands separated by isoelectric focusing demonstrates that Pduarte contributes approximately 41% as much alpha 1AT to the total serum alpha 1AT concentration as the normal "M" alpha 1AT, similar to Plowell. Direct DNA sequencing of the proband's genomic DNA demonstrates that the Pduarte allele differs from the normal M1 (V213) allele by two amino acid substitutions, R101 (CGT)-->H(CAT) and D256 (GAT)-->V(GTT). Individually, these amino acid substitutions characterize the normal M4 allele (R101-->H) and the deficient Plowell allele (D256-->V). Thus the Pduarte allele differs from the Plowell allele only by the normal allelic background in which the V256 mutation occurs. Comparison of amino acid sequences among several alpha 1AT variants demonstrates that Pduarte is an example of a more general observation regarding diversity within the PI (protease inhibitor) system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364591 TI - A molecular approach to estimating the human deleterious mutation rate. AB - We propose a method of measuring the human genomic deleterious mutation rate based on comparison of the rate of evolution per nucleotide per generation of neutral sequences, microN, with the overall rate of evolution of unique sequence DNA, microO. Data on microN, which are based on pseudogenes, permit an estimate of the total zygotic (twice the genomic) mutation rate, UT = 2 microNn = 2(2 x 10(-8)(3 x 10(9)) approximately 10(2), where n is the number of nucleotides per genome. Data on microO can be obtained by comparison of representative samples of relatively short homologous sequences from the genomes of Homo and a related species. The fraction of the genome that is controlled by negative selection is fS = (microN - microO)/microN and the deleterious zygotic mutation rate, the expected number of new deleterious alleles carried by a zygote, is US = UTfS. If fS > 0.01, US > 1, which would have important implications for human genetics and evolutionary biology. PMID- 8364592 TI - Caveat to genotype-phenotype correlation in mucopolysaccharidosis type II: discordant clinical severity of R468W and R468Q mutations of the iduronate-2 sulfatase gene. PMID- 8364593 TI - Phenylalanine hydroxylase gene: a novel splice mutation in intron 2 in two German and Polish families with severe phenylketonuria. PMID- 8364594 TI - Biomechanics of pitching with emphasis upon shoulder kinematics. AB - The American Sports Medicine Institute conducts research to increase understanding of mechanisms involved in upper extremity injuries to throwing athletes. This paper presents a qualitative overview of pitching and a detailed quantitative description of arm motion about the shoulder during this highly dynamic activity. Data on kinematics of arm motions about the shoulder are presented for 29 elite throwers. The major motion about the shoulder is external/internal rotation. Scapulothoracic and glenohumeral flexibility permit the arm to reach an externally rotated position of 175 degrees. Approximately 30 msec before release, the arm internally rotates 80 degrees, reaching peak angular velocities near 7,000 degrees/sec. In rehabilitation of injured throwers, there is a need to appreciate the highly dynamic nature of this skill and to attempt to simulate these dynamic motions and loads as part of the final phase of treatment before the athlete returns to competition. PMID- 8364595 TI - Arthroscopic examination of the throwing shoulder. AB - Throwing athletes may develop a multitude of problems in the glenohumeral joint and subacromial area. On occasions when rehabilitation is unsuccessful, diagnostic arthroscopy and arthroscopic management of these disorders may be indicated. The present study demonstrates several common injury patterns noted on arthroscopic examination of the throwing shoulder. PMID- 8364596 TI - Classification and treatment of rotator cuff injuries in the overhand athlete. AB - Rotator cuff injury in athletes results from accumulation of microtrauma to both the static and dynamic stabilizers of the shoulder. Our classification of these injuries and treatment protocol is based on knowledge of the pathophysiology of events leading to rotator cuff failure. Rotator cuff disease is attributed to one of five different modes of failure: primary compressive disease, secondary compressive disease, primary tensile overload, secondary tensile overload, and macrotraumatic injuries. Although disease is categorized based on a single failure mode, there is often significant overlap between the mechanisms of injury leading to the disease. Categorization and, consequently, treatment of the injury rely upon proper identification of the primary pathology and an understanding of the causative factors leading to rotator cuff failure. In most cases conservative management is successful, but, in the refractory cases, minimally invasive surgical techniques have also been successful in returning most athletes to a premorbid level of function. PMID- 8364597 TI - Rehabilitation of the shoulder following rotator cuff injury or surgery. AB - Rotator cuff problems are encountered frequently and must be rehabilitated precisely. The pace and intensity of the program are regulated by the degree of pathology and the patient's activity requirements. As our ability to understand the biomechanics of shoulder motion improves, we realize that many rotator cuff problems are secondary to instability. This instability can be subtle. The following article details a rehabilitative program for patients with rotator cuff pathology and includes both conservative and postoperative programs for pathology secondary to instability as well as primary impingement. PMID- 8364598 TI - Classification and treatment of shoulder dysfunction in the overhead athlete. AB - There are two distinct pathological categories of shoulder injury. In the older population, shoulder injury is generally a result of the degenerative aging process. In the younger population, it is commonly a result of the repetitiousness of an overhead sport. In the latter group, instability is typically the core problem, leading to the continuum of subluxation, impingement, and rotator cuff tear. A classification scheme, proposing four definitive types of shoulder injury, assists in directing an effective management program. Once diagnosed (the first step of treatment) a conservative rehabilitation program that emphasizes strengthening of the glenohumeral protectors, scapulohumeral pivotors, humeral positioners, and power drivers is advised. The surgery of choice, for the small minority who fail to respond to the rehabilitation program, is the anterior capsulolabral reconstruction. A sports medicine team working together with the athlete is instrumental in his/her return to sport. PMID- 8364599 TI - Rehabilitation for the overhead athlete. AB - Rehabilitation of the shoulder of the overhead athlete has undergone significant changes during the past few years. This article illustrates shoulder problems related to repetitive overhead activities, such as throwing. Additionally, we present basic science contributions in this area, principles of shoulder rehabilitation, and a comprehensive rehabilitation program for the symptomatic or asymptomatic athlete based on these principles. PMID- 8364600 TI - Neuromuscular testing and rehabilitation of the shoulder complex. AB - The shoulder complex plays an integral role in performing an athletic skill involving the upper extremity. The intricacy of the neuromotor components controlling shoulder motion and athletic skill is an issue that the sports physical therapist deals with on a daily basis when rehabilitating athletic patients. The purpose of this article is to review neuromotor control of the shoulder complex and describe an exercise routine developed to enhance proprioception, kinesthesia, and neuromuscular control. Clinical research studies examining the strength of the rotator cuff and scapular stabilizers, in addition to joint position sense, are reviewed. The results of these studies are discussed as they apply to the exercises described in the article designed to improve dynamic stability. The results of these studies and implementation of these exercises will help the sports physical therapy clinician assist the athletic patient and improve dynamic and neuromotor control of the shoulder. PMID- 8364602 TI - Regulated expression of the rat medium chain hydrolase gene in transgenic rape seed. AB - Medium chain hydrolase (MCH) is an enzyme which regulates the chain length of fatty acid synthesis specifically in the mammary gland of the rat. During lactation, MCH interacts with fatty acid synthase (FAS) to cause premature release of acyl chains, thus providing medium chain fatty acids for synthesis of milk fat. In this study we have investigated the ability of rat MCH to interact with the phylogenetically more distant FAS structure present in plant systems and to cause a perturbation of fatty acid synthesis. In in vitro experiments, addition of purified MCH to rapeseed homogenates was found to cause a significant perturbation of fatty acid synthesis towards medium chain length products. The rat MCH gene was expressed in transgenic oilseed rape using a seed specific rape acyl carrier protein (ACP) promoter and a rape ACP plastid targeting sequence. Western analysis showed MCH protein to be present in transgenic seed and for its expression to be developmentally regulated in concert with storage lipid synthesis. The chimaeric preprotein was correctly processed and immunogold labelling studies confirmed MCH to be localized within plastid organelles. However, fatty acid analysis of oil from MCH-expressing rape seed showed no significant differences to that from control seed. PMID- 8364601 TI - Positive-negative selection gene targeting with the diphtheria toxin A-chain gene in mouse embryonic stem cells. AB - The diphtheria toxin A-chain gene was used in a positive-negative selection gene targeting vector to alter the CD4 gene which is transcriptionally silent in mouse embryonic stem cells. Expression of the toxin gene was driven by a constitutively active enhancer, yet the targeting construct exhibited only minimal transient toxicity while enriching for targeted clones 9- to 29-fold. Germline transmission of the stem cell-derived genome was obtained. These data suggest the usefulness of this diphtheria toxin A-chain cassette in replacement-type positive-negative selection vectors. Its potential for novel applications, particularly in the enrichment for 'hit-and-run' insertion-type vectors, is discussed. PMID- 8364603 TI - Degeneration of skeletal and cardiac muscles in c-myb transgenic mice. AB - In order to reveal cellular processes sensitive to abnormal c-myb expression in vivo, transgenic mice were produced by introducing the c-myb nuclear proto oncogene under the ubiquitous transcriptional regulatory unit of the cytoplasmic beta-actin gene. Expression of c-myb in thymus did not cause apparent abnormality, but the mice unexpectedly developed degenerative abnormalities in skeletal and cardiac muscles; this occurred predominantly in males. Expression of c-myb in skeletal muscle was correlated with an inflammation of muscle and was accompanied by vacuolar degeneration of muscle fibres, their regeneration, and lymphocyte infiltration. The identical pathological progression in cardiac muscle was associated with cardiomegaly. PMID- 8364604 TI - Pharmacokinetics of radioiodinated human and ovine growth hormones in transgenic mice expressing bovine growth hormone. AB - Pharmacokinetics of radioiodinated human growth hormone (hGH) and ovine growth hormone (oGH) were studied in normal mice and in transgenic mice carrying the bovine growth hormone (bGH) gene fused to phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK-bGH). Multiexponential plasma decay curves were obtained in both normal and transgenic mice after a 125I-oGH injection and pharmacokinetic parameters were estimated by fitting blood concentration data to a three compartment model. The half-life for the rapid compartment was shorter in transgenic than in normal mice (t1/2 gamma: 1.2 +/- 0.3 vs. 2.2 +/- 0.5 min). The slow compartment had a t1/2 alpha of 160 +/- 23 min for transgenic and 70 +/- 8 min for normal mice while the middle compartment had a t1/2 beta of approximately 10 min for both groups of mice. The mean residence times were 167 +/- 24 and 55 +/- 5 min for transgenic and normal mice, respectively. Specific liver uptake of radioactivity after injection of 125I-oGH or 125I-hGH was found in both groups of animals. Specificity studies indicated that, similarly to normal mice, livers of transgenic mice possess a mixed population of somatotropic and lactogenic receptors. Uptake of labelled hGH by the liver was dose-dependent and the doses that prevented 50% of liver uptake (ED50%) were 8 and 165 micrograms per 50 g body weight for normal and transgenic mice, respectively. These in vivo results confirm and extend previous in vitro findings that a life-long excess of bGH increases hepatic somatotropic and lactogenic receptors. Since elevation in growth hormone (GH) receptors was reported to be associated with an increase in GH binding protein (GHBP), we suspect that both the increase in the mean residence time and the reduction in specific uptake of GH in the livers of transgenic mice may be the result of an increase in GHBP levels. PMID- 8364605 TI - Assembly of an antibody and its derived antibody fragment in Nicotiana and Arabidopsis. AB - The yield and assembly of an IgG1 antibody and its derived F(ab) fragment were compared in Nicotiana and Arabidopsis. The results obtained showed a lot of interclonal variability. For 45% of the primary transgenic calluses, antigen binding entities represented less than 0.1% of the total soluble protein (TSP). Only two of the 103 analysed transformants contained more than 1% of antigen binding protein, with 1.26% being the highest yield. Analogous amounts of complete antibody and F(ab) accumulated in primary callus tissue. Moreover, yields were in the same range for both species as far as primary callus tissue is concerned. However, the accumulation of the F(ab) fragment in leaf tissue of regenerated plants differed significantly between Nicotiana and Arabidopsis. The F(ab) fragment accumulated to only 0.044% of TSP in Nicotiana leaves but up to 1.3% in Arabidopsis leaves. Furthermore, both species showed differences in the assembly pattern of the complete antibody. Whereas Arabidopsis contained primarily fully assembled antibodies of 150 kDa, Nicotiana showed an abundance of fragments in the 50 kDa range. PMID- 8364607 TI - [The ontogeny of the origin of different forms of higher nervous activity]. PMID- 8364606 TI - A series of vectors that simplify mammalian gene targeting. AB - In order to facilitate the procedure of mammalian gene targeting, we have produced and functionally tested a series of generic vectors. Homologous recombination has been achieved with each vector. The vectors are designed for both replacement and insertional recombination, are suitable for 'hit and run' strategies and contain all necessary genetic elements for both positive-negative and promoterless/gene fusion enrichment of homologous integrations. Multiple unique restriction sites are included to simplify the incorporation of genomic targeting sequences. PMID- 8364608 TI - [The sexual cycle in reflexively ovulating rabbits]. AB - Reflexo-ovulating rabbits appeared to have oestrous and ovarian 11-12-day cycles. The condition of external sexual organs revealed the hormonal status and ovarian folliculogenesis, being an adequate index of the cycle stage. No release of preovulatory gonadotropin or spontaneous ovulation occurred in natural oestrus due, probably, to inadequate production of the pituitary gonadotropins and to low progesterone level in the blood during oestrus. PMID- 8364609 TI - [A device for determining the latency time of the reactions resulting from nerve resection]. PMID- 8364610 TI - [The formulation of the conditions for the chromatographic separation of adrenal cortex mineralo- and glucocorticoids and androgens using the Milichrome chromatograph]. PMID- 8364611 TI - [Patterns in the correlations between the indices of the hydration-electrolyte profile of the brain]. AB - The hydration-electrolyte profile was studied in 18 CNS structures of dogs. The frequencies of correlation coefficients were found to be placed in diminishing order as follows: H2O/H2O, K/K, H2O/K, Na/Na, H2O/Na, Na/K. The closest relations were detected in the frontal cortex, the least number of interactions were characteristic of the spinal cord and the hippocampus. The interrelations based on functional, anatomic, embryo-phylogenetic principles were most frequently observed in the thalamic and caudate-frontal systems as well as in the cortex and in mesencephalon. PMID- 8364612 TI - [The effect of ethanol on carboxypeptidase H activity in the hypophysis and some sections of the brain in rats under different stressful exposures]. AB - The combined effect of ethanol and stress induced a hyperactivation of the carboxypeptidase H in some areas of the rat brain. The carboxypeptidase H in supposed to be involved in regulation of the ethanol effect on the organism during stress. PMID- 8364613 TI - [The neuronal background impulse activity of the cerebellar dentate nucleus in the rat]. AB - The analysis of serial correlograms of spontaneous neuronal activity of the rat cerebellum dentate nucleus revealed six main dynamic versions of the impulse flows. Independent haphazard distribution of interspike intervals, irregular sequences of short and long intervals, periodic changes of the impulse flow rate, were predominant. PMID- 8364614 TI - [The functional properties of the cochlear-vestibular acupuncture points of the external auditory canal]. AB - Endaural acupuncture points were studied in 60 healthy subjects. The points were found to have obvious advantages as compared with the commonly accepted points of the ear. PMID- 8364615 TI - [The developmental dynamics of the erythroid stem cell in rat hematopoietic organs in ontogeny]. AB - The cellular composition of peripheral blood, hematopoietic organs, and the content of erythroblastic islands of the red bone marrow revealed regular changes of concentrations of the RBCs, hemoglobin and reticulocytes thus corroborating the phenomenon of "early postnatal anemia" in rats. A considerable increase in number of the erythroblastic islands was revealed between the 10th and 45th days of life. Functional reconstruction of the islands in the postnatal ontogenesis was analysed in rats. PMID- 8364616 TI - [The role of the cerebral cortex venules in normal oxygen transport and in normobaric hyperoxia]. AB - Mathematical processing revealed no statistically significant dependence of the oxygen tension distribution (pO2) over the wall of the vessel under study upon its diameter. The data obtained showed that, in hyperoxemia, oxygen diffusion from the blood to tissues occurs through the walls of the radial venules. In case the distance between arteriole and venule is less than 100 mcm, a diffuse shunt is possible. PMID- 8364617 TI - [Postural systemic vascular reactions]. AB - Changes of hydraulic resistance of the vascular system were studied under conditions of stabilised blood expenditure in response to ortho- and antiorthostatic effects. The first type effects involved an increase in the resistance whereas the antiorthostasis decreased the resistance. Both ways of estimation of vascular responses are discussed from the standpoint of conditions for baroreflex control of vasomotor responses. PMID- 8364618 TI - [The phasic contraction of the guinea pig vas deferens in organotypic culture during periodic stretching]. AB - Vas deferens explants from the adult guinea pigs were cultivated under organotypic conditions with repeated stretching. In control explants with no stretching over 9 days the occurring hypersensitivity is similar to the denervated one. Simultaneously phase component contractile response decreased in a 5.25 time. Repeated stretch preserve the hypersensitivity and more increased contractile response, however normalization of the phase component contractile. PMID- 8364620 TI - [The mechanisms of the dominant and thirst motivation]. PMID- 8364619 TI - [Endogenous peptides as a single system of regulatory substances]. AB - Endogenous peptides of the whole organism, irrespective of the place of their synthesis, mostly play the role of the elements constituting a code for triggering the integrative mechanisms of regulation of the functions of organs' systems or the whole organism. The data is presented on the results of radio immunological assessment of concentration changes in the regulatory peptides in response to effect of the substances introduced into the vascular bed of animals. PMID- 8364621 TI - [Liudvig Martynovich Pussep on Ivan Pavlovich Pavlov]. PMID- 8364622 TI - [Epiphyseal interrelations with the striatum in the haloperidol-induced catalepsy model]. AB - Removal of the rat pineal gland entailed an attenuation of haloperidol-induced catalepsy and readjustment of its time-course. This may depend on either direct of indirect effects of the pineal factors, mostly in the ventral portion of the striatum whose hyperactivity determines the main parameters of the neuroleptic effect. PMID- 8364623 TI - [The ultrastructure of smooth muscle cells under static stretching]. AB - Smooth muscle cells of the guinea pig vas deferens in the organotypic culture change their phenotype from the contractile to the synthetic one within a month. The activating nucleoli, while increasing the number of free ribosomes and endoplasmic reticulum, decreased the amount of myofilaments and dense bodies. Longitudinal static stretching maintains the contraction phenotype in the longitudinal layer muscle but not in the circular layer. PMID- 8364624 TI - [Age-related changes in the parameters of the capillary blood flow in rat skeletal muscle: allometric relations and the hypothesis of capillary functional length]. AB - The effect of growth on the capillary i.d. and density, the RBC velocity and tube hematocrit in the rat m. cremaster was studied in vivo. All these parameters decreased with growing as described by allometric equations. The mean capillary diameter and the hematocrit did not change significantly under the same conditions. A hypothetic explanation of the discrepancy between the bulk flow and capillary flow is suggested. PMID- 8364625 TI - [Functional changes in the mucosa of the small intestine of sturgeons in toxic exposures]. AB - Exposure to toxic effect of sulfate lignin induced swelling of mucous folds and separate epithelial cells in the sturgeon gastrointestinal tract's mucous membrane. Cholinesterase was found in epithelial layers under the toxic effect. Participation of the meta-sympathetic nervous system in organisation of the intestinal tissue responses to unfavourable effects is discussed. PMID- 8364626 TI - [The thermogenic characteristics in the early ontogeny of rats developing normally and under conditions of decreased uterine-placental blood circulation]. AB - The brown adipose tissue was shown to be the main source of heat production in 1 day old rats, whereas by the 4th day their heat production becomes associated with non-contractile as well as contractile thermogenesis. Retarded rats revealed a disturbed adaptation to ambient conditions and they were unable to maintain their temperature homeostasis. PMID- 8364627 TI - [The reaction of gonadal endocrine function in mink to the administration of chorionic gonadotropin under artificial lighting conditions]. PMID- 8364628 TI - [A method for conducting mass cardiac monitoring]. PMID- 8364629 TI - [The interaction between physiological disciplines and scientific schools in the development of evolutionary physiology]. PMID- 8364630 TI - [The contribution of the schools of L. A. Orbeli and V. N. Chernigovskii to the development of the physiology of the autonomic nervous system]. PMID- 8364631 TI - [In the history of science there are events that determine the development of a new scientific direction]. PMID- 8364632 TI - [On the way to the centenary of I. P. Pavlov's theory of conditioned reflexes. Fragments from history]. PMID- 8364633 TI - [The importance of I. P. Pavlov's theory of conditioned reflexes in the emergence of a system of neurosciences]. PMID- 8364634 TI - [Psychic functional operators in the classical salivary conditioned reflex]. PMID- 8364635 TI - [The neurophysiological correlates of the organization and functioning of the cortical-caudate system in the formation and realization of conditioned-reflex behavior]. PMID- 8364636 TI - [The history and outlook of research into the localization and organization of cerebral functions]. PMID- 8364637 TI - [The conditioned reflex principle and the physiology of behavior]. PMID- 8364638 TI - [Dmitrii Stepanovich Fursikov (on the centenary of his birth)]. PMID- 8364639 TI - [The conditioned reflex in the systems organization of behavioral acts]. PMID- 8364640 TI - [The Madrid speech of I. P. Pavlov and the psychophysiology of behavior]. PMID- 8364641 TI - [The conditioned reflex in the biology and genetics of behavior]. PMID- 8364642 TI - [The conditioned reflex as an instrument of research into the role and mechanisms of the participation of the brain in the structuring of behavior]. PMID- 8364643 TI - [What can be written about human higher nervous activity in a work devoted to experimental results in animals?]. PMID- 8364644 TI - [The structural-functional bases of behavior]. PMID- 8364645 TI - [The formation of natural food conditioned reflexes in early ontogeny]. PMID- 8364646 TI - [The neurophysiological and neuropharmacological analysis of conditioned reflex activity in primates]. PMID- 8364647 TI - Ethical nursing. PMID- 8364648 TI - Caring for your back. PMID- 8364649 TI - Managing venous ulcers. PMID- 8364650 TI - Nursing overseas. Saving Somalis. PMID- 8364651 TI - It's all in the attitude. PMID- 8364652 TI - Practising safely. PMID- 8364654 TI - Similar problems face all nurses. PMID- 8364653 TI - A professional struggle. Interview by Teresa O'Connor. PMID- 8364655 TI - Professional development. The Canterbury experience. PMID- 8364656 TI - Professional development. A personal perspective. PMID- 8364657 TI - A cultural question. PMID- 8364658 TI - [Knee arthroplasty with total condylar endoprosthesis]. AB - Authors report on experiences gained with the Total Condylar knee prosthesis, representing the third generation in the development of the knee endoprosthesis. Based on results of 17 operations it is stressed that after the implantation in the severely degenerated or destroyed knee joint they succeeded to reach a significant decrease of pain and increase of the range of movement. After the implantation of the prosthesis adequate stability can be gained in knee joints without cruciate ligaments. PMID- 8364659 TI - [Low contact stress knee prosthesis system. Results and complications]. AB - This paper reports on the global results of the low contact stress knee prosthesis system with mobile weight bearing surfaces. The follow-up result of 918 cemented and 963 cementless knee prostheses was in more than 90 per cent excellent and good 2-8 years after the operation. The ratio of complications connected with the construction decreased to 2.8 per cent in cementless prostheses. In the cemented series less variations of size were available and the problems with the tibial component were under 2, the complications with the patella remained under 1 per cent. The more than 12 years clinical use of the mobile weight bearing knee prosthesis system proved the success of the solution concerning the basic construction. PMID- 8364660 TI - [Experience with the implantation of porous coated hip endoprostheses and primary stability of implantation]. AB - The use of porous coated cementless prosthesis, shows a worldwide spread in consequence of the advantages given by the "live" connection between the implant and the bone. Based on 40 implantations of prostheses of this type (Duraloc 1200 acetabulum, AML shaft) authors report on the technique of the implantation and the primary stability reached. In consequence of the formation, the variety of size and the properly usable instruments for implantation, the prostheses could be used for every kind of deformed, dysplastic hips and good primary stability was reached in every case operated. PMID- 8364661 TI - [Does the flexed position of the wrist releave the stress on the suture in the flexor tendon?]. AB - Authors have examined the optimal position of the wrist from the viewpoint of active motion during the postoperative care, after the suture of the flexor tendons of the hand. Based on clinical and cadaveric experiences a motion of the wrist (inverse) in contrary direction to the motion of the fingers is suggested i. e. flexion of the fingers in wrist extension and vice versa. The tendon injuries distally and proximally from the wrist are discussed separately. PMID- 8364662 TI - [Experience with the management of fractures of the distal tibial end penetrating into the joint]. AB - Authors made a follow-up of the pilon fractures treated in the National Institute of Traumatology during the five years period of 1983 through 1987. 43 of them could be controlled after 4-8 years personally. A radiological follow-up result of at least 1-2 years was nearly in all cases available. The surgical therapy in this period was almost exclusively stable osteosynthesis. Fixateur externe was used only exceptionally. On the basis of their results it is thought that in the treatment of pilon fractures the stable osteosynthesis with exposure should have an important role in the future too. PMID- 8364663 TI - [The Boichev-Andreev surgical method in the management of recurrent post traumatic shoulder dislocations]. AB - In the Boitchev-Andreiev operation the tip of the coracoid with the muscles having their origin here, is chiselled and after a transduction under the subscapular muscle it is refixed to its original place. One relapse from 28 cases was found in a mean follow up time of 3 years, in 2 cases subluxation was found. The average limitation of lateral rotation was 6.4 degrees. In the total follow up out of 28 cases 23 could be classified as good, 3 adequate and 2 poor. PMID- 8364664 TI - [Management of idiopathic femur head necrosis in adults using Sugioka's femur osteotomy method]. AB - Authors report on the results achieved with Sugioka's osteotomy in 20 cases. In the stage III or less and if the damage of the femoral head was less than 100 degrees, the result of the operation was good or excellent. The operation performed with adequate indication proved to be effective. PMID- 8364665 TI - [Significance of arthroscopy at the Orthopedic Department of a county hospital]. AB - Author reports on the 300 arthroscopic examinations and operations performed in the Orthopaedic Department of the Salgotarjan County Hospital. He states that in possession of instruments they have now a diagnostic possibility, more sure and informative than all possibilities before. This gives, according to their practical experience, the freedom of operation without arthrotomy too. It is stressed that the modern orthopaedic care by now requires regular arthroscopic activity on the level of county hospitals in this country. PMID- 8364666 TI - [Management of 2 cases of pseudarthrosis]. AB - Authors describe their standpoint concerning the choice of therapeutic methods in the solution of two cases of the lower leg's pseudarthrosis. On the basis of two cases treated successfully they strive after osteogenetic induction and adequate stability and in the formation of principles after the equilibrium of modernity and rationality. PMID- 8364667 TI - [Epidemiology of hand injuries in Vas County based on a survey]. AB - Authors have found in a 1 year survey in the county Vas 7580 hand injuries. The major proportion of young men and adolescents in the material was conspicuous. The types of accidents were investigated together with the place of the accident and types of the injury. The material shows that in contrary to the work accidents in the recent past the number of the accidents at home has increased- and so their prophylaxis became the main point. PMID- 8364668 TI - Clinical practice guidelines: a curse or a cure? PMID- 8364669 TI - Guidelines for the transfer of critically ill patients. Guidelines Committee, American College of Critical Care Medicine, Society of Critical Care Medicine and the Transfer Guidelines Task Force. AB - OBJECTIVE: The development of practice guidelines for the conduct of intra- and interhospital transport of the critically ill patient. DATA SOURCES: A task force of experts in the field of patient transport drawn from the membership of the Society of Critical Care Medicine and the American Association of Critical-Care Nurses provided the personal experience and published literature from which these guidelines were developed. STUDY SELECTION: Study design was not a factor in selecting the literature to validate the experts' personal experience. The lack of well-designed clinical outcome studies was an important factor in determining the method of practice policy development utilized. DATA EXTRACTION: The expert task force met and developed a draft of these guidelines based on their experiences and the available literature. This draft document was then reviewed by an additional group of experts whose input was used by the task force to develop this final consensus report. RESULTS OF DATA SYNTHESIS: Each hospital should have a formalized plan for intra- and interhospital transport that addresses the following elements: pretransport coordination and communication, transport equipment, accompanying personnel, monitoring during the transport and documentation. The transport plan should be developed by a multidisciplinary team and should be evaluated and refined by the continuous quality improvement process. CONCLUSION: The available data has allowed the authors to develop an evidence-based practice policy for the intra- and interhospital transport of the critically ill. PMID- 8364670 TI - TIPS: a new alternative for the variceal bleeder. AB - BACKGROUND: Standard medical therapies for variceal bleeding secondary to portal hypertension (vasopressin, esophagogastric balloon tamponade and sclerotherapy) are associated with high rates of recurrent bleeding. Surgical shunting has a mortality rate of 15% to 50%. The transjugular intrahepatic portosystemic shunt offers a novel, minimally invasive procedure for nonsurgical portal decompression. METHOD: Following catheterization of the hepatic vein from a jugular vein approach, a needle is directed fluoroscopically from the hepatic vein into a branch of the portal vein along an intrahepatic tract. The intrahepatic tract is then dilated and held open with a stainless steel stent delivered on a balloon catheter. This creates a portosystemic shunt entirely within the liver. RESULTS: The collective experience of more than 300 cases from several centers has been reported. The technical success rate for the transjugular intrahepatic portosystemic shunt is 92% to 96%. Thirty-day mortality rates range from 0% to 14%, with less than 3% attributed to procedural complications. Primary shunt patency is about 90%, with a secondary patency rate of 100%. Rates of encephalopathy and rebleeding are 9% to 14%. Ascites resolves in 80% to 90% of patients. CONCLUSION: The transjugular intrahepatic portosystemic shunt appears to be a safe and effective procedure for management of variceal bleeding and holds promise for becoming the treatment of choice for portal hypertension. PMID- 8364671 TI - Evaluation and revision of a vasopressin/nitroglycerin protocol for use in variceal bleeding. AB - BACKGROUND: Continuous infusion of IV vasopressin have been widely used to lower portal pressure and reduce bleeding from esophageal varices. Recently, the combination of vasopressin and nitroglycerin has been noted to be superior to vasopressin alone. This is due to the ability of nitroglycerin to reduce the detrimental effects of vasopressin while preserving its beneficial effects. In September 1989 the authors initiated a protocol in the medical intensive care unit of a large university teaching center that directed caregivers in the simultaneous use of vasopressin and nitroglycerin for use in variceal bleeding. OBJECTIVE: To determine whether the protocol was being used correctly and whether the addition of nitroglycerin produced the desired cardiovascular effects. METHOD: Nineteen patients (25 separate episodes) assigned to the vasopressin/nitroglycerin protocol were monitored retrospectively over a 20-month period for a total of 1068 hours of vasopressin/nitroglycerin infusion. Twenty four patients received nitroglycerin at 10 to 50 micrograms per minute, 13 at 50 to 100 micrograms per minute and 6 at 100 to 400 micrograms per minute. RESULTS: Nitroglycerin dosage was not advanced appropriately in 78% of episodes despite evidence of bradycardia, hypertension and peripheral vasoconstriction. CONCLUSIONS: Revision of the protocol, giving additional guidance to clinicians on assessment and nitroglycerin advancement, was necessary and was accomplished. PMID- 8364672 TI - The effect of positioning on hemodynamics and gas exchange in the critically ill: a review. AB - Positioning of critically ill patients affects hemodynamic and cardiopulmonary outcomes. A review of clinical studies indicates that backrest elevations up to 60 degrees do not affect measurement of intracardiac pressures or cardiac output, but PaO2 may diminish in sitting positions following surgical procedures. In lateral positions, measurement of intracardiac pressures and cardiac output is not recommended, since a uniform reference point has not been identified for lateral positions. In patients with unilateral lung disease, PaO2 increases with the unaffected lung in the dependent position. Despite widespread use, the Trendelenburg position has not been shown to provide consistent beneficial effects. Prone positioning may be beneficial in adult respiratory distress syndrome and in weaning of mechanically ventilated patients. When planning positioning maneuvers, critical care nurses should consider these effects in relation to the specific needs of each patient. Hemodynamic and cardiopulmonary responses to positioning should be evaluated in conjunction with other therapeutic modalities such as those designed to preserve skin integrity and improve comfort. PMID- 8364673 TI - Withdrawal of mechanical ventilation: ethical principles and guidelines for terminal weaning. AB - BACKGROUND: Discontinuation of mechanical ventilation because of the recognition of futility of continued treatment or because of patient or family request is an increasingly frequent occurrence in critical care. Although there is broad consensus about the patient's right to refuse life support, little has been written about the actual procedure of withdrawing mechanical ventilation. OBJECTIVE: The purposes of this article are: (1) to review ethical arguments supporting the view that it may be morally permissible to withdraw mechanical ventilation from patients who are neither terminally ill nor imminently dying and (2) to provide guidelines for the procedure of ventilator withdrawal. METHOD: Ethical principles supporting the position that ventilator withdrawal under these conditions can be morally justified and principles suggesting that ventilator withdrawal is morally objectionable are evaluated. Factors contributing to clinicians' ambivalence about this issue and guidelines for planning and implementing treatment withdrawal are discussed. PMID- 8364674 TI - Epidemiology, pathophysiology and clinical presentation of gram-negative sepsis. AB - OBJECTIVE: To review the epidemiology and pathophysiology of gram-negative sepsis and the new consensus terminology describing the clinical signs of sepsis. DATA SOURCES: Review of the medical literature and compiled data from animal and clinical trials. PARTICIPANTS: Members of the Society of Critical Care Medicine, American College of Chest Physicians and American Association of Critical-Care Nurses with expertise on the subject of sepsis and its complications. RESULTS: Preconference and general sessions were offered at the National Teaching Institutes of the American Association of Critical-Care Nurses, with the goal of clarifying the epidemiology, risk factors and pathophysiology of gram-negative sepsis. In addition, current terminology and new (1992) consensus terminology describing the clinical signs of sepsis were presented. Special emphasis was placed on the role of the healthcare provider in the prevention and recognition of sepsis and the role of the septic mediators in the septic cascade. CONCLUSIONS: If the incidence of sepsis is to be reduced, the healthcare provider must be aware of the risk factors for sepsis and methods of reducing nosocomial infections. A thorough understanding of the role of mediators and consensus terminology used to describe sepsis, severe sepsis, septic shock and multiple organ dysfunction syndrome is necessary to recognize early or progressive signs of sepsis and to initiate state-of-the-art therapy. PMID- 8364675 TI - Nurses' beliefs and attitudes toward visiting in adult critical care settings. AB - OBJECTIVE: To assess the beliefs and attitudes of critical care nurses about the effects of visiting on patients, staff and family. DESIGN: Both interviews and questionnaires were used to gather data on nurses' attitudes and beliefs about visiting and open visiting according to the format of Ajzen and Fishbein's Theory of Reasoned Action. SETTING: Five Utah intensive care units and three Ohio intensive care units. SAMPLE: Critical care nurses in Utah (N = 29) and Ohio (N = 41) were interviewed to assess their beliefs about the effects of visiting on patients, families, nurses and nursing care delivery. RESULTS: Nurses believed the consequence of visiting was more positive for the patient from a psychological perspective than from a physiological perspective but that the effects might differ depending on the patient, the visitor and the circumstances. They believed that visiting had negative consequences for families, because they became exhausted, and that visiting was disruptive for nursing care delivery. Their attitudes about effects of visiting on nursing staff were consistently more negative than were attitudes about the effects on the patient and the family. CONCLUSION: To provide an optimal situation for visiting, its negative consequences must be minimized and nurses' attitudes and beliefs about visiting must be assessed and addressed. PMID- 8364676 TI - The relationship of child acuity, maternal responses, nurse attitudes and contextual factors in the bone marrow transplant unit. AB - PURPOSE: This study was designed to examine the relationships between maternal perceptions of an acutely ill child, nurse caregivers and contextual factors in a pediatric critical care unit. METHODS: Subjects were mothers of 20 children who had had their first bone marrow transplant and the primary nurse of each child. The study was conducted on a bone marrow transplant unit. Variables included the acuity of the child, maternal satisfaction with nursing care, maternal vigilance as measured by the time spent at the child's bedside, nurses' attitudes toward family involvement with care, nursing experience and bone marrow transplant unit variables (census, unit acuity and staffing deficit). RESULTS: Positive associations were observed between the child's acuity and maternal satisfaction with nursing care, and between maternal vigilance and staffing deficit. There was an inverse relationship between maternal vigilance and length of nursing experience of the primary nurse and between positive attitudes of nurses toward family participation and years of nursing experience. CONCLUSION: These results show the complex nature of parental perceptions and involvement in the hospitalized child's care. They suggest that maternal attitudes about caregiving are associated with the child's acuity and that maternal vigilance is related to nursing and environmental factors, principally critical care experience of the primary nurse. PMID- 8364677 TI - Pacemaker update. Part IV: Antitachycardia devices. PMID- 8364678 TI - Severe anemia in the Jehovah's Witness: case report and discussion. AB - Major blood loss following trauma is common, but severe anemia is generally not life-threatening when managed with the administration of blood and blood products. Severe anemia becomes particularly challenging and potentially lethal when the patient is a Jehovah's Witness, for whom receiving a transfusion is contrary to religious principles. This case report describes the management and hospital course of a Jehovah's Witness who was seriously injured in an airplane crash. PMID- 8364680 TI - The hippocampus and space: are we flogging a dead (sea-)horse? PMID- 8364679 TI - Hippocampal morphology and spatially related behavior in Long-Evans and CFY rats. AB - Behavioral responses to novelty in an open field and spatial learning in a radial maze with four arms out of eight reinforced were tested in male and female CFY and Long-Evans rats. Subsequently, the sizes of the total hippocampi and of various hippocampal cell layers and terminal fields at the midseptotemporal level were measured in Timm-stained sections. No strain differences were found in the open field (except for defecation). In the radial maze, Long-Evans rats showed better spatial reference memory capabilities than rats of the CFY strain. The relative sizes of the intra- and infrapyramidal mossy fiber (IIP-MF) projections did not differ between the strains. Within the more variable CFY strain, a positive correlation between the size of the IIP-MF projection and radial maze performance was found. The absolute sizes of the entire hippocampi and all hippocampal layers at the midseptotemporal level were larger in the CFY strain. The size of the suprapyramidal mossy fiber projection was related to the number of granule cells and to the ratio between granule and CA3 pyramidal cells. In contrast, the size of the IIP-MF projection did not correlate with either of these variables. The results indicate that the size of the mossy fiber projection may be determined mainly by the available postsynaptic surface on the dendrites of CA3 pyramidal neurons. Furthermore, an increased number of granule cells and their larger projection to the apical dendrites of pyramidal neurons does not appear to result in physiological changes with behavioral consequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364681 TI - Modification of the responses of hippocampal neurons in the monkey during the learning of a conditional spatial response task. AB - In order to analyze the function of the hippocampus in learning, the activity of single neurons was recorded while monkeys learned a task of the type known to be impaired by damage to the hippocampus. In the conditional response task, the monkey had to learn to make one response when one stimulus was shown, and a different response when a different stimulus was shown. It had previously been shown that there are neurons in the hippocampal formation that respond in this task, to, for example, a combination of a particular visual stimulus that had been associated in previous learning with a particular behavioral response. In the present study, it was found that during such conditional response learning, the activity of 22% of the neurons in the hippocampus and parahippocampal gyrus with activity specifically related to the task altered their responses so that their activity, which was initially equal to the two new stimuli, became progressively differential to the two stimuli when the monkey learned to make different responses to the two stimuli. These changes occurred for different neurons just before, at, or just after the time when the monkey learned the correct response to make to the stimuli. In addition to these neurons, which had differential responses that were sustained for as long as the recordings continued, another population of neurons (45% of those with activity specifically related to the task) developed differential activity to the two new stimuli, yet showed such differential responses transiently for only a small number of trials at about the time when the monkey learned. These findings are consistent with the hypothesis that some synapses on hippocampal neurons modify during this type of learning so that some neurons come to respond to particular stimulus-response associations that are being learned. Further, the finding that many hippocampal neurons started to reflect the new learning, but then stopped responding differentially (the transient neurons), is consistent with the hypothesis that the hippocampal neurons with large sustained changes in their activity inhibited the transient neurons, which then underwent reverse learning, thus providing a competitive mechanism by which not all neurons are allocated to any one learned association or event. PMID- 8364682 TI - Changes in protein kinase C isozymes in the rat hippocampal formation following hippocampal lesion. AB - The cellular and regional distribution of the four protein kinase C (PKC) isoforms in the rat hippocampal formation and the response of PKC to lesions were determined by employing immunohistochemical and immunochemical techniques with antibodies specific to PKC(alpha), -(beta I), -(beta II), and -(gamma). PKC(alpha) intensely stained the periphery of the pyramidal cell in the stratum pyramidale. The granule cells, glial cells, and mossy fibers were anti-PKC(alpha) negative. The cytoplasm, axons, and dendrites of basket cells and interneurons in the hilus were labeled with anti-PKC(alpha). Anti-PKC(beta I) immunoreactivity was localized on the periphery of pyramidal cells and interneurons of the hilus, as well as the oriens, radiatum, and molecular layers of the CA regions. Anti PKC(beta II) immunoreactivity was mainly cytoplasmic, extending into the dendrites in the hippocampal pyramidal cells and the dentate granule cells, and also in some glial cells. In the stratum radiatum of the CA1, anti-PKC(gamma) immunoreactivity localized to the pyramidal cell cytoplasm, extending into the dendrites. Following fimbria-fornix (FF) lesions, the anti-PKC(alpha) and -(beta I) staining of the pyramidal cell periphery was markedly reduced. The anti PKC(gamma) staining of the pyramidal and granular cells of the dentate gyrus was reduced whereas the interneuron staining in the hilus was increased. In the FF lesioned hippocampus, anti-PKC(alpha) and anti-PKC(beta II) labeled reactive glial cells, whereas anti-PKC(beta I) and -(gamma) did not. Quantitative Western blot analysis revealed a dramatic increase in the particulate/total PKC for all isozyme forms, although the total levels of PKC, except PKC(gamma), did not change following FF lesions. The PKC(gamma) concentration doubled after FF lesions. Perforant path lesions resulted in a marked alteration in the neuronal staining in dentate gyrus with anti-PKC(alpha) and -(beta I) and in increased numbers of anti-PKC(alpha)- and anti-PKC(beta II)-positive glial cells. Anti PKC(gamma) staining did not change noticeably. The total PKC concentration did not change for isozymes alpha, beta I, and gamma, but PKC (beta II) concentration increased by 48% following perforant path lesions as detected by Western blot analysis. The particulate/total PKC decreased for all four isozymes although the reduction in PKC(beta I) concentration was not statistically significant. This change in PKC compartmentalization is in marked contrast to an increased level of particulate PKC following FF lesions. Thus, the effects of deafferentation and deafferentation for each PKC isoform were different. PMID- 8364683 TI - Hippocampal plasticity induced by primed burst, but not long-term potentiation, stimulation is impaired in area CA1 of aged Fischer 344 rats. AB - The effect of two types of electrical stimulation designed to induce long-lasting plasticity of the Schaffer/commissural inputs to CA1 pyramidal neurons was investigated using in vitro hippocampal slices made from young (3-6 month) and old (24-27 month) Fischer 344 rats. The first stimulation paradigm, primed burst (PB) stimulation, consisted of a total of five physiologically patterned stimuli: a single priming pulse followed 170 ms later by a burst of four pulses at 200 Hz. The second stimulation paradigm, long-term potentiation (LTP) stimulation, consisted of a 200 Hz/1 second train (a total of 200 stimuli). Primed burst and LTP stimulation were equally effective at inducing a lasting increase in the population spike recorded from slices made from young rats. However, the enhancement of population spike amplitude produced by PB, but not LTP, stimulation was significantly less in slices made from old rats. These results suggest that the capacity of the hippocampus to demonstrate long-lasting synaptic plasticity is not altered with age, but that engaging plasticity-inducing mechanisms becomes more difficult. Furthermore, these data suggest that physiologically patterned paradigms for inducing long-lasting synaptic plasticity may more accurately assess the functional status of hippocampal memory encoding mechanisms than does conventional LTP stimulation. PMID- 8364684 TI - Adenosine-induced suppression of synaptic responses and the initiation and expression of long-term potentiation in the CA1 region of the hippocampus. AB - The results of several previous studies have suggested that pretreatment with adenosine can block the induction of long-term potentiation (LTP), although other studies have found no effect of adenosine on the induction of LTP. The interaction of adenosine with the induction of LTP in the rat hippocampal slice was investigated. Inhibition of synaptic responses by adenosine either prior to or immediately after high-frequency or theta-burst stimulation did not affect LTP measured after washout of the adenosine. The only conditions under which adenosine blocked the development of LTP was when it was given 3-5 minutes prior to the stimulation train. To understand how it was possible to induce LTP, during the period 1-3 minutes following adenosine when synaptic responses were virtually eliminated, evoked responses during the 100 Hz stimulation train were recorded. Although synaptic responses to low-frequency stimulation were virtually eliminated by adenosine, they reappeared during high-frequency stimulation. These results suggest that although adenosine can depress synaptic responses, an increase in neurotransmission during a high-frequency train can partially overcome this effect of adenosine, and the hypothesis that adenosine can selectively block LTP is not supported. PMID- 8364685 TI - Spiny neurons of area CA3c in rat hippocampal slices have similar electrophysiological characteristics and synaptic responses despite morphological variation. AB - Area CA3c is an area of morphologically diverse neurons. In addition to the presence of interneurons and pyramidal cells that are similar to those found in other subfields of area CA3, many neurons of area CA3c are different. They do not resemble interneurons, since they bear numerous spines, yet they also differ substantially from pyramidal cells in their morphology. To determine if the variants of area CA3c spiny cells are distinct physiologically as well as morphologically, intracellular recordings were made to record the electrophysiological properties of area CA3c cells in rat hippocampal slices, and each cell was identified morphologically following intracellular dye injection. The results show that the spiny cells, regardless of their often extensive morphological variation, have relatively uniform, pyramidal-like electrophysiological properties. The aspiny cells are quite different from the spiny cells morphologically (i.e., in their paucity or complete lack of spines), and are also extremely different electrophysiologically, exhibiting features of "fast-spiking" cells. Thus, spiny cells in area CA3c correspond to cells with pyramidal-like electrophysiology, and the aspiny cells in area CA3c correspond to cells with interneuronal physiological properties. This correlation between structure and function appears to be a rule that pertains to each of the subfields of the hippocampus. PMID- 8364686 TI - Herring antifreeze protein: primary structure and evidence for a C-type lectin evolutionary origin. AB - A complementary DNA (cDNA) for a type II antifreeze protein (AFP) was isolated from an Atlantic herring liver cDNA library and sequenced. The predicted protein sequence is homologous to those of the type II fish AFP from smelt and sea raven; it is also homologous to the carbohydrate recognition domains (CRD) of calcium dependent (C-type) lectins and similar domains in lectin-like proteins. Herring belong to the infradivision Clupeomorpha, which is distinct from the Euteleostei to which all other AFP-producing fish belong. The occurrence of type II AFP in widely divergent fish groups and their homology to C-type lectin CRDs suggest that type II AFPs evolved from these lectins. Amino acid residues forming the hydrophobic cores of rat mannose-binding protein A (MBP-A) that are conserved in character among C-type lectins are also conserved in the herring AFP. The herring AFP also requires Ca2+ for thermal hysteresis activity. These results suggest that herring AFP is structurally and functionally similar to the CRDs of C-type lectins and related domains in other proteins. PMID- 8364687 TI - Molecular cloning and sequencing of omul prolactin cDNA. AB - We constructed a complementary DNA (cDNA) library from Baikal omul (Coregonus autumnalis migratorius Georgi) pituitary glands. Synthetic oligonucleotide probes corresponding to chum salmon prolactin (PRL) cDNA were used to select the recombinant plasmids carrying the omul PRL gene. The larger insert was sequenced and found to encode a polypeptide of 210 amino acid residues, including a putative signal sequence of 23 amino acids. Nucleotide and predicted amino acid sequence of omul PRL showed high homology with other salmonid PRLs. PMID- 8364688 TI - Interspecific and intrapopulation variation in mitochondrial ribosomal DNA sequences of Mytilus spp. (Bivalvia: Mollusca). AB - A 560-base pair portion of the mitochondrial 16S ribosomal DNA (16S rDNA) from three morphologically similar mussels, Mytilus edulis, M. galloprovincialis, and M. trossulus, was amplified with the polymerase chain reaction, and 349 base pairs were sequenced. These data showed that this gene in M. edulis and M. galloprovincialis has not diverged; however, the north Pacific mussel, M. trossulus, showed fixed differences from M. edulis and M. galloprovincialis at 5 nucleotide positions. Furthermore, the population of M. trossulus at Tillamook Bay, Oregon, was found to contain two very divergent 16S rDNA genotypes that differ at 37 nucleotide positions. Thus, intraspecific variation in this gene in M. trossulus is greater than that seen interspecifically in M. edulis and M. galloprovincialis. Despite this large difference, in the absence of evidence of genetic isolation between these groups of M. trossulus, no taxonomic changes are proposed. These data are consistent with a north Pacific origin of the genus with subsequent dispersal to the Atlantic Ocean across the Artic Sea, giving rise to M. edulis in northern Europe and subsequently M. galloprovincialis in southern Europe and the Mediterranean Sea. PMID- 8364689 TI - Identification and localization of bacterial endosymbionts in hydrothermal vent taxa with symbiont-specific polymerase chain reaction amplification and in situ hybridization techniques. AB - Invertebrates that contain endosymbiotic chemoautotrophic eubacteria are widely distributed in a variety of reducing marine habitats, including deepsea hydrothermal vents. The mechanisms of symbiont transmission in these invertebrates are not understood. To test the hypothesis that symbionts are transmitted via the eggs of hosts, we used group-specific hybridization probes complementary to 16S ribosomal RNAs (rRNAs) to look for symbionts in eggs and ovaries. 16S rRNA sequences were examined for domains unique to the symbionts of three vent animals: Calyptogena magnifica, Bathymodiolus thermophilus, and Riftia pachyptila. Three 16S rRNA-directed oligodeoxynucleotide hybridization probes (CG 1255R, RP-1243R, BT-1255R) specific for these endosymbionts were synthesized and evaluated by dot-blot hybridization. At higher stringencies, all three probes showed a high degree of specificity for their target endosymbionts rRNAs. The probes were also used as polymerase chain reaction (PCR) primers for detection of the symbiont 16S rRNA genes in genomic DNA isolated from host tissues known to contain symbionts. All three symbiont-specific probes were highly sensitive and specific as PCR primers; they successfully amplified 1 pg target DNA. However, all amplifications of extracted egg DNA from the vestimentiferan R. pachyptila with either universal eubacterial (Eub A/B) or the Riftia symbiont-specific (RP 1243R/Eub B) primer sets were unsuccessful. Nonradioactive in situ hybridizations were performed on ovarian tissue from the vestimentiferan Ridgea piscesae using RP-1243R, 3' end-labeled with digoxigenin-11-dUTP (Boehringer Mannheim). The probe was subsequently detected with an alkaline phosphatase-conjugated immunoglobulin G antibody specific for the digoxigenin moeity. The probe bound only to the tissue of R. pisceasae coincident with the known location of symbiont cells and was not detected in any region of the ovary. These data indicate that transovarial symbiont transmission in the vestimentiferans does not take place and that symbiont acquisition is probably a post-spawning event. PMID- 8364690 TI - Codon usage in bony fishes. AB - Bony fishes are excellent experimental models that have been used extensively in biochemical and molecular genetic studies. As proteins are isolated and characterized from these organisms, information on codon usage by bony fishes can be used for subsequent recombinant DNA studies. Codon usage and nucleotide bias within codons from three species of bony fishes and two composites of 14 and 15 bony-fish species were analyzed. Although differences in codon usage increased from seven amino acids between fish species to eight amino acids between fish genera, the small number of differences (3 amino acids) between a single species and a fish composite minus that species suggests that codon usage tables constructed from large numbers of fish species are representative of bony fish in general. Furthermore, we found few differences in codon usage between two vertebrate phyla (fish and rat). Codons in fish DNA sequences end predominantly in G or C, even though the coding sequences are not enriched in these nucleotides. This positional base bias can be used to locate putative protein coding regions in fish DNA sequences. PMID- 8364691 TI - Molecular phylogenetic position of hexactinellid sponges in relation to the Protista and Demospongiae. AB - Although it is generally accepted that the first multicellular organisms arose from unicellular ancestors, the phylogenetic relationships linking these groups remain unclear. Anatomical, physiological, and molecular studies of current multicellular organisms with relatively simple body organization suggest key characteristics of the earliest multicellular lineages. Glass sponges, the Hexactinellida, possess cellular characteristics that resemble some unicellular protistan organisms. These unique sponges were abundant in shallow seas of the early Cambrian, but they are currently restricted to polar habitats or very deep regions of the world oceans. Due in part to their relative inaccessibility, their potential significance to the early phylogeny of the eukaryotic kingdoms has been largely overlooked. We used sequences of the 18s ribosomal RNA gene of Farrea occa, a representative of the deep-water hexactinellid sponges, and Coelocarteria singaporense, a representative of the more common demosponges, and compared them with selected ribosomal RNA gene sequences available within the Protista. Using four computational methods for phylogenetic analysis of ribosomal DNA sequences, we found that the hexactinellid sponge-demosponge cluster is most closely related to Volvox and Acanthamoeba. PMID- 8364692 TI - Expression and inheritance of RSVLTR-rtGH1 complementary DNA in the transgenic common carp, Cyprinus carpio. AB - Transgenic common carp, Cyprinus carpio, possessing the long terminal repeat (LTR) sequence of avian Rous sarcoma virus (RSV) fused to the rainbow trout (rt) growth hormone (GH1) complementary DNA (cDNA) were produced by microinjection. Initial studies showed that the transgenic common carp transmitted the foreign DNA to a significant fraction of their progeny in three of four crosses of transgenic males with control females. These progeny grew 20 to 40% faster than their nontransgenic full siblings. In this study, additional experiments were conducted to evaluate inheritance and expression of the foreign GH gene in transgenic common carp, and the growth performance of these transgenic fish. Four P1 (parental generation produced by microinjection) x nontransgenic controls, four P1 x P1, and one P1 x F1 matings of transgenic carp containing RSVLTR-rtGH1 cDNA were made. The percentages of transgenic progeny resulting from these matings were: 0, 32, 42, 100 (4 progeny only), 21, 21, 31, 30, and 23%, respectively. All crosses except 1 siblot (control x P1) exhibited progeny ratios below the expected 50 or 75% transgenic. These results indicate that most of these transgenic P1 had the foreign gene in their germ line but were mosaics, and at least one transgenic individual did not have the RSVLTR-rtGH1 cDNA in the gonadal tissue. Both P1 and F1 transgenic fish produce trout growth hormone mRNA and polypeptide as determined by reverse transcription polymerase chain reaction amplification, RNA dot-blot hybridization, and radio-immunobinding assay. Growth response by families of F1 transgenic fish to the addition of rtGH1 cDNA varied widely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364693 TI - A comparison of molluscan (Bivalvia) phylogenies based on palaeontological and molecular data. AB - The 18S rRNA gene from three scallop species (Placopecten magellanicus, Chlamys islandica, Argopecten irradians) and 7 mactrid clam species (Spisula solida, S. subtruncata, S. solidissima, Mactromeris polynyma, Tresus nuttallii, T. capax, Mulinia lateralis) have been fully sequenced. Phylogenetic analyses have supported the scheme of Waller (1991) for the Pectinidae but conflict with current evolutionary concepts and classification within the Mactridae. The Mactridae are shown to have evolved monophyletically. The current subfamilial position of Mactromeris, and the subgenera Spisula and Hemimactra of the genus Spisula, are not supported by this data. PMID- 8364694 TI - Enhanced incorporation of transgenic DNA into zebrafish chromosomes by a retroviral integration protein. AB - Manufacture of lines of fish containing specific transgenes is difficult because most fish that hatch from embryos injected with foreign DNA are mosaic; few have the transgenic DNA integrated in germ-line cells. To determine whether the process of integration of exogenously supplied DNA into fish genomes could be accelerated, we examined the ability of the Moloney murine leukemia virus (MoMLV) integration protein (IN) to function in embryonic zebrafish cells. We used partially purified IN from a baculovirus/insect cell expression system and unpurified IN from extracts of psi-2 mouse cells that carry a MoMLV provirus. Both forms of IN were able to enhance expression in zebrafish 10 days after fertilization. At day 14 of development, fish injected with IN had higher levels of transgenic DNA than control fish. The ability of IN to enhance integration of transgenic constructs was demonstrated by a ligation-mediated polymerase chain reaction procedure, which was employed to detect junction fragments of foreign and host genomic DNA, generated by IN-mediated integration. PMID- 8364695 TI - Rapid identification of yeast species using three primers in a polymerase chain reaction. AB - Classic methods for identification of yeasts rely on a variety of morphological and physiological tests that often take days to weeks to complete. We have been able to reduce the time to less than one day through the use of multiple segment specific oligonucleotide priming of a region of the large subunit rDNA in a polymerase chain reaction. The "hot start" reaction was used with two universal external delimiting primers and one internal species-specific primer. Five specific primers were tested: a primer for a biologically similar group of Rhodotorula species, a generic (Cystofilobasidium) primer, and 3 species-specific primers (Leucosporidium scottii, Cryptococcus muscorum, and Rhodotorula mucilaginosa). In the absence of specific target DNA, the universal rDNA segment is amplified; in the presence of target DNA, the specific primer region is amplified. The technique is accurate within two base position differences when a 24 nucleotide-specific primer is used. The technique should be applicable to other marine eukaryotes. PMID- 8364696 TI - [Issues of nursing science toward the year 2000]. PMID- 8364697 TI - [A study of changes in the nutritional status of patients receiving cancer chemotherapy]. AB - In an attempt to find a method for effective nursing support which would maintain a favorable nutritional status in patients receiving chemotherapy, the nutritional status of 15 patients with lung cancer receiving cisplatin therapy was evaluated, and the factors influencing their status were studied. (1) Nutritional status was evaluated in terms of 7 indicators: body weight, skinfold thickness, arm muscle circumference, grip strength, hemoglobin level, serum total protein and serum albumin. Among these, skinfold thickness proved to be the most sensitive indicator of the changes in nutritional status of cancer patients during chemotherapy. (2) Multiple regression analysis revealed that skinfold thickness was influenced by dietary intake, which in turn was related to nausea, vomiting, trait anxiety level estimated by STAI and maximum body temperature associated with infection. (3) It was concluded that the following nursing interventions are significant for maintenance of favorable nutritional status for cancer patients during chemotherapy. First, periodic evaluation of their nutritional status by anthropometric measurements is necessary. Secondly, efforts should be made to reduce nausea and vomiting, to reassure patients with severe anxiety so that they become mentally stable, and to motivate the patients to perform self-care for prevention of infection, thereby achieving a sufficient dietary intake. PMID- 8364699 TI - [Trends in research--an analysis of studies published in the Journal of Japan Academy of Nursing Science from 1987-1992]. PMID- 8364700 TI - [Confronting ethical issues among Japanese nurses and their responses]. PMID- 8364698 TI - [Effects of music on relieving pain associated with a compulsory posture]. AB - To assess the role of music on pain management, we examined effects of music to relieve a pain associated with a compulsory posture. Classical musics, which are recognized to make persons feel well, were chosen in this study. Five healthy adult females kept a supine position for 2 hours without music. Complains, and variations of heart beat and respiration were observed in each individual during the 2 hour experiment. After 5 days or more, these subjects had the same experience with music. Frequency and intensity of complains were significantly diminished by music. Heart rate was not changed by music. Respiration rate was increased in 3 subjects with music. Frequency of irregular respiration was significantly decreased by music. There was a positive correlation between frequency of irregular respiration and number of complaints in subjects kept without music. The present study demonstrated that music is effective to relieve a pain associated with a compulsory posture. Our results suggest that music plays a significant role on pain management in palliative therapy. PMID- 8364701 TI - Smoking in pregnancy. PMID- 8364702 TI - Clinical and genetic aspects of myotonic dystrophy. AB - Myotonic dystrophy is the commonest inherited muscle disease of adults. It causes significant clinical features in many organ systems and requires a broad-based approach for optimum management. Recent genetic advances promise to provide exciting new insights into the pathophysiology of the disease and may allow rational treatments to be developed. PMID- 8364703 TI - Dystrophia myotonica and difficult intubation. PMID- 8364704 TI - The gut and the skin. AB - Many disorders of the gastrointestinal tract have cutaneous manifestations. In this article the skin signs and diseases that are most commonly associated with gastrointestinal disease are described. PMID- 8364705 TI - Management of meningococcal infections. AB - The last 5 years has seen an increase in the number of cases of meningococcal infection. Despite the availability of highly active antibiotics, the mortality from this infection remains at 10%, rising to 40% in patients presenting in severe shock. Here we describe the spectrum and pathophysiology of meningococcal infections, and the most important aspects of treatment and management. PMID- 8364706 TI - Medical futility in context. PMID- 8364707 TI - The malignant thyroglossal cyst. PMID- 8364708 TI - Violence against doctors. PMID- 8364709 TI - Peer review of almighty judgments. PMID- 8364710 TI - Acoustic neuroma: triumphs outnumber the disasters. PMID- 8364711 TI - Retaining RHAs: iconoclastic support--and criticism. PMID- 8364712 TI - Retaining RHAs: iconoclastic support--and criticism. PMID- 8364713 TI - Retaining RHAs: iconoclastic support--and criticism. PMID- 8364714 TI - The alternative to magic medicine. PMID- 8364715 TI - Paedomorphosis and simplification in the nervous system of salamanders. AB - Comparative neuroanatomists since Herrick [1914] have been aware of the paradox that the brain of amphibians, especially salamanders, is less complex than one would expect based on their phylogenetic position among the Tetrapoda. Many features of the brain are less differentiated in salamanders than in tetrapod outgroups, including chondrichthyans and bony fishes, and for some brain characters, the salamander brain is even more simple than that of the agnathans. Here, we perform a cladistic analysis on 23 characters of four sensory systems (visual, auditory, lateral line and olfactory) and the brain. Our taxa include myxinoids, lampreys, chondrichthyans, actinopterygians, Latimeria, Neoceratodus and the lepidosirenid lungfishes, amniotes, frogs, caecilians, salamanders and bolitoglossine salamanders. Of the 23 characters we examined, 19 are most parsimoniously interpreted as secondarily simplified in salamanders from a more complex ancestral state, two characters are equally parsimonious under both hypotheses, one character (well developed ipsilateral retinotectal projections) is more complex in bolitoglossine salamanders than in vertebrates generally, and only one character (migration of neurons in the medial pallium) is most parsimoniously interpreted as retention of the plesiomorphically simple condition. Secondary simplification of the salamander brain appears to result from paedomorphosis, or retention of juvenile or embryonic morphology into adulthood. Paedomorphosis is correlated with an increase in genome size, which in turn is positively correlated with cell size, but negatively correlated with cell proliferation and differentiation rates. Available data suggest that, although increasing genome size and paedomorphosis tend to compromise the function of the salamander brain, compensating mechanisms have evolved that may restore or even enhance brain function. PMID- 8364717 TI - A prey-type dependent hypoglossal feedback system in the frog Rana pipiens. AB - Nerve transection experiments combined with high-speed videography and electromyography were used to characterize a prey-type dependent hypoglossal feedback system which coordinates mouth opening and tongue protraction in the common leopard frog, Rana pipiens. When feeding on small prey, sensory feedback from the tongue through the hypoglossal nerve is necessary to trigger mouth opening. If sensory feedback is prevented from reaching the brain by transection of the hypoglossal nerve, then the mouth fails to open although the feeding behavior appears otherwise normal. However, when feeding on large prey, the mouth opens normally even after the hypoglossal nerve has been transected. Thus, peripheral feedback is not necessary to trigger mouth opening when feeding on large prey, and presumably a central coordination mechanism is used. In Rana pipiens, the evolution of a new tongue morphology and a new motor pattern for feeding on small prey has been accompanied by the evolution of a novel, peripheral mechanism for coordinating tongue protraction and mouth opening. However, the primitive motor pattern for feeding on large prey and the primitive coordinating mechanism have been retained. These results imply that the neural circuits producing the different motor patterns for large and small prey are anatomically distinct at some level in the central nervous system. If they are not anatomically distinct, then sensory feedback should be necessary to trigger mouth opening regardless of which motor pattern is being expressed. While the anatomy of these distinct pathways remains to be elucidated, these results suggest that novel neural circuits may in fact underlie different behaviors even when they seem, superficially, to be relatively similar. PMID- 8364716 TI - Comparison of behavioural and morphological measures of visual acuity during ontogeny in a teleost fish, Forsterygion varium, tripterygiidae (Forster, 1801). AB - Ocular morphology was examined in larval, juvenile and adult F. varium. There was a 26-fold increase in eye size from 0.28 mm in the smallest larva (5.0 mm in length) to a maximum diameter of 7.2 mm in a 110 mm long adult. Larval fish had pure cone retinae at hatching, however, putative rod precursor cells were also present. Juvenile and adult fish had a duplex retina with cones arranged in a square mosaic in which 4 equal double cones surrounded a central single cone. Hypertrophy of cone ellipsoids with increasing eye size resulted in maintenance of a closely packed array in fishes of all sizes. Theoretical sensitivity, assessed in terms of convergence of rods:bipolars, rod density, and photoreceptor outer segment length, increased during the juvenile phase but was constant across the adult size range. Angular density of cones increased with increasing eye size such that theoretical spacial acuity was poor in smallest fish (1 degree 8') and improved to an asymptotic value of about 9' in adults. Behavioural acuity of a 1 day-old larva determined using the optokinetic response (29 degrees), was very much poorer than histological estimates (1 degree 8'). Behavioural acuity improved to 4 degrees 18' at 14 days of age, compared to a theoretical value of 54'. An estimate of Matthiessen's ratio based on histological measurements suggests that the larval eye is initially strongly myopic, and grows into focus. Development of the retractor lentis muscle was first apparent 7 days after hatching with the result that larval eyes are incapable of accommodative lens movements to correct for a refractive error. This apparent myopia is thought to account for at least part of the mismatch between theoretical and behavioural spatial acuity. PMID- 8364718 TI - Kindling in the perirhinal cortex. AB - In vitro experiments have indicated that the perirhinal cortex is highly excitable and its relationship to the basolateral amygdala and piriform cortex is altered by previous amygdala or dorsal hippocampal kindling. As a result, we felt it was important to assess the excitability of the perirhinal cortex in vivo by comparing its kindling profile to that of the basal amygdala, piriform cortex or dorsal hippocampus. We observed that the after-discharge (AD) threshold of the perirhinal cortex was higher than the other 3 structures but the AD duration was not different. Subsequently, the perirhinal cortex kindled more rapidly than the other 3 structures, and with extremely short latencies to onset of forelimb clonus. With the view that synchronized discharge in the perirhinal-piriform area provides the critical trigger for limbic kindled convulsions, the relationship of kindling rate and convulsion latencies and durations between the 4 structures was discussed. PMID- 8364719 TI - A cholinergic antagonist, mecamylamine, blocks light-induced fos immunoreactivity in specific regions of the hamster suprachiasmatic nucleus. AB - Recent studies have shown that light-induced phase shifts of the circadian rhythm of locomotor activity are associated with c-fos expression in the suprachiasmatic nucleus (SCN) of rodents. In order to explore further the importance of c-fos expression for the phase-shifting effects of light, we examined the effects of mecamylamine on light-induced Fos-like immunoreactivity (Fos-lir) in the SCN. Mecamylamine was chosen because it is a cholinergic antagonist that blocks the phase-shifting effects of light on the circadian activity rhythm in the golden hamster. Golden hamsters were entrained for at least 14 days to a 14 h light: 10 h dark photoperiod. Animals were then placed in constant darkness (DD) and during exposure to DD were subjected to one or more of the following treatments: (1) vehicle alone; (2) mecamylamine alone (450 micrograms, i.c.v.) at circadian time (CT) 19; (3) vehicle plus a light pulse at CT 19; (4) mecamylamine 10 min prior to the light pulse at CT 19. Mecamylamine blocked the phase-shifting effects of light on the circadian rhythm of locomotor activity when compared to vehicle treated animals (P < 0.001). A light pulse at CT 19 induced Fos-lir in the SCN within 1 h, whereas treatment with vehicle or mecamylamine had no noticeable effect on Fos-lir in the SCN. Mecamylamine pretreatment dramatically reduced light-induced Fos-lir in the SCN by 75%. The most striking observation was the clear inhibition of Fos-lir by mecamylamine in the dorsomedial region of the SCN while there was little inhibition of Fos-lir in the most ventral portions of the SCN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364720 TI - Behavioural responses of bicucculline methiodide injections into the ventral hypothalamus of freely moving, socially interacting rats. AB - Several studies, using electrical stimulation of parts of the hypothalamus, have shown, that different parts of the hypothalamus yield different behavioural responses upon stimulation. In order to differentiate between stimulation of neuronal cell bodies and passing fibres and to investigate the role of GABA in hypothalamically elicited behaviour, 25 local injections with bicucculline methiodide, a GABA antagonist, (35 ng/0.2 microliter) were performed in the ventral parts of the hypothalamus of 16 freely moving rats in a social environment. A cannula system was used that allowed injection without interruption of the ongoing social interactions. Digging, gnawing, drinking and attack behaviour were elicited in different animals. By plotting the behavioural responses of the animals into a detailed hypothalamic atlas, we assessed the hypothalamic distribution of the elicited behavioural responses. A number of injections elicited a combination of two or three different responses, probably due to diffusion of the substance, thus disinhibiting more than one behavioural system. Our results are in general agreement with previous electrical stimulation data and show that, in an overlapping pattern, different populations of neurons are involved in the elicitation of digging, gnawing, drinking and attack behaviour. In the hypothalamus, a tonic GABAergic inhibition of neurons involved in the display of these types of behaviour appears to exist. PMID- 8364721 TI - A cellular model of oxidant-mediated neuronal injury. AB - Oxidants derived from the partial reduction of oxygen are thought to play a significant role in neuronal injury. We present here a cellular model of neuronal injury mediated by hydrogen peroxide (H2O2) using the PC 12 rat pheochromocytoma cell line. The organization of microtubules and microfilaments within neurites of PC 12 cells differentiated by exposure to nerve growth factor was examined after H2O2 injury using fluorescence microscopy. Concentrations of H2O2 as low as 100 microM produced an initial periodic pattern of microtubule depolymerization over 3-4 h which later progressed to complete depolymerization. Neuritic microspikes containing actin filaments were relatively more resistant to injury by H2O2 than microtubules. Blebbing of PC 12 cell bodies and neurites also was seen after H2O2 injury and the blebs appeared to contain microtubules. The destructive changes affecting neuritic structure preceded but were not essential for PC 12 cell lysis. Exposure of the cells to the Ca2+ ionophore, ionomycin (25 microM) also produced the same pattern of microtubule depolymerization in PC 12 neurites as was seen after H2O2 injury suggesting that H2O2 may mediate its destructive effect on the neurites via elevation of intracellular Ca2+. PMID- 8364722 TI - Influence of phenytoin on cytoskeletal organization and cell viability of immortalized mouse hippocampal neurons. AB - Phenytoin (PHT) is a commonly used anticonvulsant drug; several side effects have been described, including morphological changes in brain cortex and cerebellar neurons and teratogenic lesions in infants of epileptic mothers. Evidence of other authors indicate that PHT may exert its action through the modification of phosphorylation patterns of cytoskeletal polypeptides. We have studied the influence of the anticonvulsant drug phenytoin on immortalized mouse hippocampal neurons in culture. This was done by means of MTT-assays, immunocytochemical and immunoblot analyses, measurements of cell metabolism, measurements of the length of neuronal processes, and electron microscopy. A distinct and pronounced effect of PHT could be characterized with regard to the formation of neuronal processes, involving malfunction of an assembly-mechanism of cytoskeletal constituents. These accumulated within appendages (blebs) or cytoplasmic condensations, instead of forming normally organized processes. However, PHT did not interfere with bulk synthesis of cell proteins and specific cytoskeletal components. PMID- 8364723 TI - Rapid increases in cerebellar Purkinje cell glutamic acid decarboxylase (GAD67) mRNA after lesion-induced increases in cell firing. AB - Loss of the inferior olive-climbing fiber input to the cerebellar cortex doubles the simple spike activity of the cerebellar Purkinje cell. There is a 3- to 4 fold increase in Purkinje cell messenger RNA for the 67 kDa form of glutamic acid decarboxylase (a synthetic enzyme for the neurotransmitter GABA) within 4-5 h of the increase in electrical activity, suggesting a rapid response of mechanisms influencing neurotransmitter synthesis or stability to altered electrophysiological activity. PMID- 8364724 TI - Target regulation of neuronal differentiation in a temperature-sensitive cell line derived from medullary raphe. AB - Following infection of dissociated embryonic day 13 rat medullary raphe cells with a retrovirus encoding the temperature-sensitive mutant of SV40 large T antigen, a clonal cell line, RN33B, was isolated by serial dilution. At 33 degrees C, RN33B cells divide with a doubling time of 48 h and show T antigen, vimentin, nestin, diffuse neuron-specific enolase, and low and medium molecular weight neurofilament immunoreactivities. RN33B cells are immortal, but not transformed, as they will not grow in soft agar. At non-permissive temperature (38.5 degrees C), T antigen expression is markedly decreased and RN33B cells cease mitotic activity and differentiate with phase bright cell bodies and 'neuritic-like' processes. Differentiated RN33B cells express enhanced neuronal specific protein expression but do not synthesize astrocytic or oligodendrocytic specific proteins. Moreover, differentiated RN33B cells returned to 33 degrees C re-express T antigen, but do not de-differentiate or begin dividing. Co-culture with embryonic hippocampus and cerebral cortex, but not medullary raphe or spinal cord, resulted in significantly greater survival, more complex neuronal morphology, and enhanced expression of neuronal-specific antigens. Immunohistochemical and Northern blot analysis revealed high levels of low affinity NGF receptor protein and mRNA in differentiated RN33B cells. PCR analysis demonstrated the presence of trkB, but not trkA or trkC, mRNA in both undifferentiated and differentiated RN33B cells. These data suggest that the observed target regulation of RN33B cell neuronal differentiation in co-culture may be mediated by neurotrophin(s). PMID- 8364725 TI - Localization of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the human hypothalamus; age-dependent colocalization with vasopressin. AB - Immunocytochemical staining, using a monoclonal antibody against corticotropin releasing hormone, was performed on hypothalami of 13 human subjects between 23 and 91 years of age who had not suffered from a primary neurological or psychiatric disease. Corticotropin-releasing hormone (CRH) immunoreactivity was present in neurons of the paraventricular nucleus (PVN) and in their fibers running to the median eminence. The CRH-positive neurons were scattered throughout the PVN, but in the rostral part relatively few cells were present. There were large individual differences in the number and staining intensity of CRH neurons in the PVN and in the staining intensity of the median eminence. These differences seemed not to be attributed to age, sex, postmortem delay, fixation time or hour of death. In the rat, too, no relationship was found between a postmortem delay of up to 24 h and CRH staining intensity of the median eminence. Since the distribution of CRH-immunoreactive neurons in the human PVN strongly overlap with vasopressin, colocalization of these peptides was investigated in a double label study and indeed found in subjects ranging between 43 and 91 years of age. However, cells staining for only one of the peptides were also observed. The vasopressin cells had a mean cellular profile area which was 2.3 times as large as the CRH cells and 2.2 times as large as the CRH and vasopressin containing neurons. In younger subjects (23-37 years of age) no colocalization of the two peptides was seen. The age-dependent colocalization of CRH with vasopressin is interpreted as a sign of increased activation of the CRH neurons with age. PMID- 8364726 TI - Inhibition by the serotonin1A agonist, 8-hydroxy-2- (di-n-propylamino)tetralin, of antidromically identified paraventricular nucleus neurons in the rat. AB - Experiments were performed using urethane-anesthetized rats to delineate the role of serotonin (5-hydroxytryptamine, 5-HT) receptors of the 5-HT1A subtype in the neural regulation of hypothalamo-pituitary-adrenocortical (HPA) secretion. The activity of single paraventricular nucleus (PVN) neurons antidromically identified as projecting to the median eminence was recorded following injection of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Intraperitoneal administration of increasing doses of 8-OH-DPAT caused dose dependent decreases in the spontaneous activity of all neurons tested. The data yielded an ED50 value of 0.19 mumol/kg for this effect. The decreases in PVN neuronal activity were accompanied by sustained decreases in mean arterial blood pressure, with an ED50 of 0.18 mumol/kg. These results provide evidence for an inhibitory role of 5-HT1A receptors in the regulation of PVN neuronal activity and support the suggestion that 5-HT may inhibit HPA secretory activity. PMID- 8364727 TI - Expression of terminin in the rat brain during neuronal differentiation. AB - Terminin is a cytoplasmic protein originally found in senescent cultured human fibroblasts. In the present study, we investigated terminin expression during development in three brain regions: the cerebral cortex, the neural retina and the cerebellum of the rat brain. By immunocytochemistry we found that terminin immunoreactivity in the brain is mainly localized in neurons. Immunoreactivity to terminin antibody was first noticed in the brain as early as embryonic day 15, and the staining intensity in the cerebral cortex reached maximum level at the first postnatal week, when the cerebral neurons become postmitotic and their synaptic connections with target cells are established. A similar pattern of terminin development was seen in the neural retinas of the same animals as well. Biochemical characterization shows that the anti-terminin antibody recognizes a 90 kDa (Tp90) and a 60 kDa (Tp60) polypeptide in immunoblots of the detergent insoluble fraction of rat brains, while Tp90 was found in the detergent-soluble fraction. Both the Tp90 and Tp60 polypeptides appeared at embryonic day 15 and reached highest levels at postnatal day 1. With the advance of further neural differentiation, however, Tp90 in the detergent-insoluble fraction diminished, and remained only in the detergent-soluble fraction. In the detergent insoluble fraction Tp60 became the predominant species during the first postnatal week. In the cerebellum, where neuronal differentiation is known to be relatively late, quantitative densitometric measurement of terminin abundance on the immunoblots showed that Tp60 in the detergent-insoluble fraction was the predominant form in the second week. Thus, the appearance of a predominant Tp60 coincided with terminal neuronal differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364728 TI - Sustained cortical metabolic responsivity to physostigmine after nucleus basalis magnocellularis ablation in rats. AB - Unilateral nucleus basalis magnocellularis (NBM) ablation, which causes partial cholinergic denervation of the ipsilateral anterior neocortex, results in an acute but transient depression of regional cerebral metabolic rates for glucose (rCMRglc) in deafferented areas; rCMRglc normalizes within 2 weeks. To seek possible compensatory changes in cholinergic mechanisms following NBM ablation that could lead to rapid metabolic normalization, we studied rCMRglc responses to the receptor agonists nicotine and arecoline and the cholinesterase inhibitor physostigmine in rats at 2 weeks after unilateral NBM destruction. Physostigmine increased rCMRglc in 10 of 30 cortical areas contralateral to the NBM lesion. Compared to the unlesioned side, rCMRglc after physostigmine in the lesioned cortex was significantly lower in 2, significantly higher in 1 and not different (P < 0.05) in 27 areas. Neither arecoline nor nicotine treatment produced rCMRglc asymmetry in lesioned rats. These results demonstrate that responsivity to physostigmine is maintained in most regions of the rat neocortex after extrinsic cholinergic denervation by NBM ablation. This adaptive response appears not to result from cholinergic receptor upregulation and may reflect instead reorganization of cholinergic synapses. PMID- 8364729 TI - Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin. AB - The interactions between 14 days of repeated restraint stress and daily administration of imipramine or tianeptine (2 h before the beginning of stress) were investigated in rats to assess responses of 5-HT2 and 5-HT1A receptors and serotonin transporter sites labelled by [3H]paroxetine in the cerebral cortex and hippocampus, two brain regions in which adrenal steroid effects on serotonin receptor-binding have been reported. 5-HT2 sites, labelled by [125I]7-amino-8 iodo ketanserin, were decreased in parietal cerebral cortex layers 3 and 5 by imipramine treatment, but not by tianeptine treatment and not by daily restraint stress. Stress, but not antidepressant, depressed 5-HT1A sites labelled with [3H]8-hydroxy-DPAT in hippocampal fields CA3, CA4 and dentate gyrus. [3H]paroxetine-binding to serotonin transporter sites was decreased by tianeptine treatment as well as by imipramine in both hippocampus and cerebral cortex, with some overlap of the fields that were significantly affected, whereas there were no effects of stress per se and no evidence of a stress x drug interaction. These results are discussed in relation to similarities and differences in the effects of different antidepressant drugs on the serotonergic system of the rat brain. Whereas the actions of imipramine and tianeptine on 5-HT2 and 5-HT1A receptors are specific to each drug, the surprising finding of a similar effect of both drugs to reduce serotonin transporter sites labelled by [3H]paroxetine suggest the possibility of a common action for these two drugs in spite of their opposite effects on serotonin re-uptake. PMID- 8364730 TI - Neuropeptide Y and optic chiasm stimulation affect suprachiasmatic nucleus circadian function in vitro. AB - The retinohypothalamic tract (RHT) is a direct pathway from the retina to the suprachiasmatic nucleus (SCN). Electrical stimulation of the optic nerve or optic chiasm activates the RHT and produces shifts in phase of a circadian rhythm in SCN neuron activity in rat hypothalamic slices in vitro. The phase response curve (PRC) for this effect is very similar to that obtained from administration of light pulses to intact animals maintained in constant darkness. The effect of optic chiasm stimulation is blocked by tetrodotoxin. In addition to the RHT, there is a second entraining pathway, the geniculohypothalamic tract, which arises from neuropeptide Y (NPY)-containing neurons of the intergeniculate leaflet of the lateral geniculate complex. In contrast to optic chiasm stimulation. NPY produces phase shifts in the rhythms of SCN neuron firing rate in vitro with a PRC that similar to that for NPY infusion into the SCN in intact animals as well as that produced by a series of treatments that induce locomotor activity. These results indicate that phase shifts of the circadian rhythm of SCN neuron activity may be produced by activation of two different entraining pathways and that the physiological actions of these pathways on pacemaker function are markedly different. PMID- 8364731 TI - Encoding of amplitude-modulated tones by neurons of the inferior colliculus of the kitten. AB - Responses of single neurons of the central nucleus of the inferior colliculus (ICC) of kittens 4-43 days of age were studied using sinusoidally amplitude modulated (AM) tones delivered monaurally or binaurally via sealed and calibrated earphones. The carrier frequency of the AM signal was set to the CF of the neuron. CFs ranged from 2-26 kHz. During the about first 2 weeks of postnatal life, ICC neurons responded to sound with periodic bursts of activity. In response to AM tones, discharges of ICC neurons at all ages studied were phase locked to the envelope of the modulation waveform over a wide range of stimulus level and modulation depth. A linear relationship, independent of SPL, was found between the average phase of discharge on the modulation cycle and modulation frequency. The slope of the line represents a time delay, which was highly correlated with the first-spike latency to tone onset, and hence with the age of the animal. The mean effective phase of the discharge remained relatively constant with age. There was little systematic change in average phase of discharge with changing stimulus level or modulation depth, although the number of spikes evoked and the temporal pattern of the spikes within a modulation cycle could vary. The sensitivity function relating spike synchrony or spike count to modulation frequency was typically band-pass in nature. The most effective modulation frequency (MEMF) was, on average, 15 Hz, far below that reported for adult cat ICC cells. When AM tones were delivered binaurally, the discharge was a periodic function of the interaural phase difference of the stimulus envelopes. The results indicate that prior to the time the cochlea is able to respond to most environmental sounds, monaural and binaural circuits involving the ICC faithfully transmit information pertaining to amplitude-modulated signals in the rate and timing of their discharges. During the next several weeks, when neural thresholds fall to adult levels, ICC circuits are activated by amplitude modulated sounds at levels encountered in the normal acoustic environment even though they are restricted to modulation frequencies below those encoded by the adult. PMID- 8364733 TI - Neurochemical evidence of functional A10 dopamine terminals innervating the ventromedial axis of the neostriatum: in vitro voltammetric data in rat brain slices. AB - The neostriatum (CPu) and nucleus accumbens (NAc) receive their primary dopamine (DA) afferents from the A9 and A10 cell groups, respectively. Anatomical evidence has, however, shown that some clusters of A10 afferents innervate the medial (periventricular) aspect of the CPu14. The present study used fast cyclic voltammetry (FCV) at carbon fibre microelectrodes to locate and measure the size of these clusters on the basis of diagnostic differences in DA efflux in A9 and A10 terminal regions. All experiments were conducted in CPu or NAc slices superfused with oxygenated artificial CSF at 32 degrees C. Carbon fibre microelectrodes were placed 80 microns below the slice surface and bipolar stimulating electrodes were located 200 microns away. Except in experiments where the stimulation frequency, pulse width or number of pulses were investigated, DA efflux was evoked using 0.1 ms, 10 mA pulses applied singly (1p) or in 20 pulse trains (20p) at 50 Hz and monitored using FCV. The CPu was first mapped on the basis of the ratio of 20p:1p DA efflux. The CPu consisted mainly (64%) of low ratio (< 3) sites while the NAc core comprised exclusively high ratio (> 6) loci. Population analysis revealed a small percentage (10%) of striatal sites with high (> 6) ratios. These high ratio sites matched the reported distribution of A10 afferent clusters, being found almost entirely along the ventromedial axis of the CPu. Individual clusters of high ratio sites (20p:1p ratios > 6), 'mapped' on the basis of evoked 20p DA efflux, were found to be irregular in outline and around 500 microns across. In order to characterise the clusters further, the influence of stimulation frequency, train duration (number of pulses) and pulse width on DA efflux were examined. Peak DA efflux in the clusters and NAc occurred at 50 Hz while the striatal matrix had a flat frequency response. Both clusters and NAc showed a similar dependence of DA efflux on the number of pulses in the stimulus train. In the CPu matrix, DA efflux was less dependent on the number of pulses. In the striatal matrix, increasing the stimulation pulse width enhanced DA efflux on trains more than on single pulses while, in both NAc and striatal clusters, there was no preferential effect on trains. The medial location of these clusters within the CPu more closely matches the anatomical distribution of the A10 afferents of Gerfen et al. than the more evenly dispersed striosomes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364732 TI - Ion transport across lingual epithelium is modulated by chorda tympani nerve fibers. AB - Each chorda tympani (CT) nerve innervates taste cells in fungiform papillae on one side of the anterior two-thirds of mammalian tongues. In this study, three effects of unilateral CT transection were investigated: (1) the persistence of taste cells on the ipsilateral and contralateral sides; (2) the ability of the CT to modulate ion transport across the ipsilateral and contralateral sides of canine lingual lingual epithelia; and (3) the effect on contralateral CT responses. Unilateral transection of dog CT caused the mean number of taste buds/fungiform papilla on the ipsilateral side to decrease from five to zero by 29-30 days after surgery. Taste buds reappeared after 44 days but in reduced numbers (two taste buds/papilla). This reappearance of taste buds after 44 days is consistent with the time predicted for the CT to regenerate and reach the anterior portion of the tongue. The number of taste buds/papilla remained unchanged on the contralateral side. Measurements of the short-circuit current (Isc) across both ipsilateral and contralateral sections of isolated canine lingual epithelia were performed at various times after unilateral CT transection. Both sides responded similarly. The Isc began to decline after 3 days, reached a minimum after approximately 18 days (approximately 40% of control Isc) and increased to control values after approximately 40 days. This includes experiments performed 30 days after surgery, when no taste buds were present on the ipsilateral side and the Isc was 80% of control values. For all times after CT transection, amiloride, an epithelial Na+ channel blocker, inhibited Isc. Thus, epithelial cells in dog tongue have amiloride-inhibitable pathways. These results show that proteins involved in active Na+ transport across lingual epithelial can be modulated by CT nerve fibers. PMID- 8364734 TI - Co-localization of peptide-like immunoreactivities with glucocorticoid receptor- and Fos-like immunoreactivities in the rat parabrachial nucleus. AB - The parabrachial nucleus (PB) is a brainstem nucleus, which mediates autonomic information from the viscera to various forebrain nuclei, e.g. to the central nucleus of the amygdala (ACe) and to the medial preoptic area (MPOA). The neurons of the PB contain several neuropeptides, of which calcitonin-gene related peptide immunoreactive (CGRP-IR) and neurotensin (NT)-IR neurons provide input to the ACe, whereas corticotropin-releasing factor-IR (CRF) neurons project to the MPOA. The aim of the present paper was to study whether the neurons containing CGRP-, NT- and CRF-like immunoreactivities (LIs) in the PB also contain glucocorticoid receptor (GR)- and/or Fos-LIs after stress. No co-localization was observed with the GR-LI and peptide-LIs, suggesting that plasma glucocorticoids do not have direct effects on these neurons of the PB. After stress, the vast majority of the peptide-IR perikarya exhibited Fos-LI, suggesting that the peptidergic pathways from the PB to ACe and MPOA are activated in stress. The ACe and MPOA have been connected in various stress related responses, e.g. inhibiting the hypothalamo pituitary-gonadal axis, raising the blood pressure and pulse, and increasing the secretion of glucocorticoids. Therefore, the activation of the peptidergic pathways between the PB and the ACe and MPOA suggests that some of these responses may be elicited by the peptidergic input from the PB. Furthermore, since Fos acts as a transcription factor, stress may affect the expression of the neuropeptides studied. PMID- 8364735 TI - Interaction of concanavalin A and wheat germ agglutinin with Helix acetylcholine receptors. AB - The effects of lectins concanavalin A (Con A) and wheat germ agglutinin (WGA), were studied on acetylcholine (ACh) responses of physically isolated internally dialyzed Helix aspersa neurons using the concentration clamp method and on the binding of [3H]alpha-bungarotoxin to the cluster of neurons. Con A and WGA have different simple sugar specificity and produced different actions on ACh-evoked Cl conductance responses, which were antagonized by Con A (5 micrograms/ml) but were not altered by WGA. Con A depressed ACh responses when applied extracellularly while it had no effect on ACh responses of the same neuron when added to the intracellular solution, thus indicating that Con A specific glycoproteins are exposed on the surface of the neuron. The studies of the effect of Con A on the properties of the ACh binding site (receptor) have demonstrated, that (1) the onset of desensitization of ACh responses of the dialyzed neurons, determined from the decay of ACh-current from peak to plateau in the continued presence of agonist and best fitted by a double exponential function, was accelerated by Con A; (2) Con A depressed the maximal ACh induced current in a dose response relationship and altered the Hill coefficients; (3) Con A depressed the binding of [3H]alpha-bungarotoxin to the cluster of neurons. These results indicate that Con A receptors on the surface of the neuronal membrane play a regulatory role in the ACh-receptor system and suggest that binding of lectin molecules to their receptors leads to inhibition of binding of ACh to ACh receptors and to acceleration of the kinetics of desensitization of ACh receptors. All the effects of Con A, that is, on the peak amplitude, desensitization, dose-response relationship of ACh induced current and binding of [3H]alpha-bungarotoxin, could be recovered by D-mannose, a competitive inhibitor of Con A binding to its receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364736 TI - Ischemic tolerance due to the induction of HSP70 in a rat ischemic recirculation model. AB - Various studies have demonstrated an increase in heat shock protein 70 (HSP70) synthesis in the brain following transiently induced ischemia, suggesting a protective role for HSP70 against ischemic insult. In this study, we determined the time course of HSP70 mRNA and protein induction in rat hippocampus following ischemia using Pulsinelli's four-vessel occlusion model, and suggested a protective role for HSP70 induction in limiting ischemic damage to neurons and delayed neuronal death. In Northern blotting analysis using human HSP70 DNA as a probe, the accumulation of HSP70 mRNA after 5 min ischemia became evident at 4 h, and continued until 16 h, while after 30 min ischemia, HSP70 mRNA appeared at 2 h, and continued above control level until 24 h after treatment. In immunoblot analysis using anti-HSP70 antibody, induction of HSP70 protein appeared 24 h and reached a maximum 48 h after 5 min ischemia. In immunohistochemical analysis using anti-HSP70 antibody, staining was not detected in CA1 neurons until 16 h after 5 min ischemia, but staining in CA1 gradually increased 1 day after ischemia and reached a maximum level 2 days after ischemia. Similar time profiles in the staining pattern of HSP70 protein were observed in CA3 and CA4 neuronal cells following 30 min ischemia. When rats pretreated with 5 min ischemia (non lethal for CA1 pyramidal neurons) were exposed to a 30 min, lethal period of ischemia, 2 days after pretreatment, considerable staining of HSP70 was observed. Pretreated rats had much less neuronal damage in the CA1 sector than did rats subjected to lethal, 30 min ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364737 TI - Intrascapular brown adipose tissue (IBAT) temperature and blood flow responses following ventromedial hypothalamic stimulation to sham and IBAT-denervated rats. AB - Intrascapular brown adipose tissue temperature (TIBAT) and capillary blood flow along with colonic (Tc) and tail (Tt) temperatures as well as blood pressure and heart rate responses were measured simultaneously in groups of age-matched, anesthetised, sham control and IBAT-denervated Long-Evans rats following VMH electrical stimulation. Unilateral VMH electrical stimulation (0.5 ms pulses of 100 microA at 50 Hz for 30 s) evoked rises in TIBAT (above core) and IBAT blood flow in the Long-Evans sham control group, along with increases in blood pressure and heart rate. Rises in IBAT temperature and capillary blood flow were absent in the surgical denervated group following VMH electrical stimulation whereas the evoked pressor and tachycardic responses were left intact and were similar to those responses seen in the sham control group. The results indicate that acute bilateral sectioning of the IBAT intercostal nerves blocks the IBAT temperature and capillary blood flow increases evoked by VMH electrical stimulation. PMID- 8364738 TI - The effects of lesions of the posterior piriform cortex on amygdala kindling in the rat. AB - The piriform cortex (PC) is thought to be critically involved in the genesis of forebrain (limbic type) seizures, including limbic kindled seizures. More recent studies have shown that the posterior PC is particularly sensitive to kindling stimulation, suggesting that the posterior PC contains specific generating sites which may be important for the stepwise progression of kindling. In the present experiments, we used microinjections of ibotenate to study the effect of selective lesions of the posterior PC on amygdala kindling in rats. Large unilateral lesions of the posterior PC and adjacent endopiriform nucleus markedly decreased the susceptibility of the ipsilateral basolateral amygdala to electrical stimulation, thus indicating that the posterior PC may normally contribute to regulation of physiologic excitability in amygdala. During kindling, rats with large lesions of the PC stayed longer in the initial phase of kindling (stage 1) than sham-lesioned controls, consistent with involvement of the posterior PC in the early stages of seizure propagation during kindling acquisition. However, the PC lesions were not capable of blocking or even severely retarding kindling. Following kindling development, rats with large lesions of the posterior PC had significantly higher focal seizure thresholds than kindled rats without lesion or rats with only small PC lesions, which suggests that the posterior PC is involved in the mechanisms which are responsible for the marked increase in seizure susceptibility induced by kindling. Taken together, the data substantiate that PC structures play a facilitatory role in kindling. PMID- 8364739 TI - Effects of the antiglucocorticoid RU 38486 on the induction of learned helpless behavior in Sprague-Dawley rats. AB - Learned helplessness (LH) is induced by exposure to an inescapable or uncontrollable stressor which results in an inability to escape or avoid the same stressor when subsequently presented in a different context. In order to understand which central mechanisms may influence the expression of the learned helpless phenotype, we have pursued an experimental approach that seeks to elucidate the behavioral effects of glucocorticoid (GC) hormones in this animal model of depression. We have previously shown that the induction of LH behavior is enhanced by adrenalectomy, an effect that is reversed by corticosterone. In this study, our aim was to attempt to locate CNS sites responsible for the observed effects of glucocorticoids on learned helpless behavior by introducing the type II GC receptor antagonist, RU 38486 to discrete brain regions. We did not observe a significant effect in LH with acute systemic, acute dentate gyrus or intracerebroventricular injection of RU 38486 in contrast to previous studies using the Porsolt swim test, another animal model of depression. However, we were able to observe a significant change upon chronic administration to the dentate gyrus. These findings suggest that glucocorticoids exert a long-term influence on stress-induced behavior, presumably by affecting glucocorticoid responsive genes in the dentate gyrus. PMID- 8364740 TI - Current source density analysis of the hippocampal theta rhythm: associated sustained potentials and candidate synaptic generators. AB - Single-electrode depth profiles of the hippocampal EEG were made in urethane anesthetized rats and rats trained in an alternating running/drinking task. Current source density (CSD) was computed from the voltage as a function of depth. A problem inherent to AC-coupled profiles was eliminated by incorporating sustained potential components of the EEG. 'AC' profiles force phasic current sinks to alternate with current sources at each lamina, changing the magnitude and even the sign of the computed membrane current. It was possible to include DC potentials in the profiles from anesthetized rats by using glass micropipettes for recording. A method of 'subtracting' profiles of the non-theta EEG from theta profiles was developed as an approach to including sustained potentials in recordings from freely-moving animals implanted with platinum electrodes. 'DC' profiles are superior to 'AC' profiles for analysis of EEG activity because 'DC' CSD values can be considered correct in sign and more closely represent the actual membrane current magnitudes. Since hippocampal inputs are laminated, CSD analysis leads to straightforward predictions of the afferents involved. Theta related activity in afferents from entorhinal neurons, hippocampal interneurons and ipsi- and contralateral hippocampal pyramids all appear to contribute to sources and sinks in CA1 and the dentate area. The largest theta-related generator was a sink at the fissure, having both phasic and tonic components. This sink may reflect activity in afferents from the lateral entorhinal cortex. The phase of the dentate mid-molecular sink suggests that medial entorhinal afferents drive the theta-related granule and pyramidal cell firing. The sustained components may be simply due to different average rates of firing during theta rhythm than during non-theta EEG in afferents whose firing rates are also phasically modulated. PMID- 8364741 TI - NMDA receptor antagonists, MK-801 and ACEA-1011, prevent the development of tonic pain following subcutaneous formalin. AB - Subcutaneous injection of formalin produces a biphasic pain response: an early, transient phase followed by a late tonic phase. The present study examined the involvement of the N-methyl-D-aspartic acid (NMDA) receptor in the development of the late pain produced following subcutaneous injection of formalin into the hind paw in mice. Blockade of the NMDA receptor by its non-competitive antagonist, MK 801, prior to formalin injection, but not after, reduced pain during the late phase. Similarly, blockade of the NMDA receptor allosteric site by the novel glycine site antagonist, ACEA-1011, also reduced the pain response in the late phase. These results suggest that the development of the late phase of formalin pain is due to NMDA-mediated activity during the early phase. PMID- 8364742 TI - Delayed matching-to-sample, object retrieval, and discrimination reversal deficits in chronic low dose MPTP-treated monkeys. AB - Cognitive deficits following chronic exposure to low doses of the neurotoxin 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in monkeys asymptomatic for a gross parkinsonian motor disorder. Monkeys developed deficits in performance of delayed matching-to-sample, visual pattern discrimination reversal, and object retrieval tasks, all tasks that rely upon the integrity of the frontal-striatal axis. Performance on a visual pattern discrimination task, that relies primarily on inferotemporal cortex function, remained intact. These results extend previous findings of frontal-like cognitive deficits in MPTP treated monkeys and further support the use of this model for studying the pathophysiology of the cognitive deficits associated with parkinsonism. PMID- 8364743 TI - Regional specificity of membrane instability in Alzheimer's disease brain. AB - We report an inherent tendency towards the destabilisation of cellular membranes in Alzheimer's disease (AD) brain. This tendency is a natural consequence of abnormal membrane lipid composition, which has previously been documented in AD. Membrane destabilisation may contribute to AD pathogenesis in its own right and may also facilitate amyloid beta-protein deposition, which is potentially neurotoxic. The instability was found to co-localise selectively with areas of neurodegeneration in AD brain, thereby possibly accounting for the focal pathology observed in this disorder. PMID- 8364744 TI - [Eulogy of Jean Roche (1901-1992)]. PMID- 8364745 TI - [Specificity of bronchopulmonary infection in cystic fibrosis]. AB - Chronic lung colonization in CF is specific and due mainly to Pseudomonas aeruginosa. Since no phagocytic or immunological abnormalities seem to be responsible for this specificity, it is possible that post-translational alterations of respiratory mucins biosynthesis occur and modify the affinity of mucins for Pseudomonas aeruginosa. PMID- 8364746 TI - [Prenatal, neonatal and postnatal prevention in cystic fibrosis]. AB - The efficiency of neonatal screening for CF could be improved by associating a molecular analysis to the immunoreactive trypsin test, on the same dried blood's sample. However the interest of such a screening for the patients benefit remains controversial. In most cases, antenatal diagnosis may be performed by a direct search of the mutation(s). However, the impact of antenatal diagnosis on CF's incidence will necessarily be limited if it can only be implemented after the birth of an affected child. Hence the interest of screening programs for the detection of healthy carriers. Carrier's detection does not raise any objection for the relatives of patients. It is still premature to recommend it to be undertaken in the general population. PMID- 8364747 TI - [Current view and outlook for cystic fibrosis therapy]. AB - Cystic fibrosis therapy has obtained in the last few years substantial benefits optimizing nutritional antibiotic and ventilatory techniques. With the discovery of the gene and of CFTR protein pharmacological approach may be initiated: correction of transmembrane ionic exchanges, and of sputum rheology. Gene therapy represents the last development, but rises methodological and ethical problems even if representing an important hope. Pulmonary transplant is only indicated in severe forms of cystic fibrosis. PMID- 8364748 TI - [Eulogy of Clement Launay (1901-1992)]. PMID- 8364749 TI - [Ocular lesions related to pellet pistols. Epidemiologic study of 160 patients]. AB - We present a retrospective study of ocular trauma related to pellet guns. During 5 years, 160 such patients were seen in our emergency unit. 80% of cases were men, and range age was 28 years. Ocular trauma circumstances was a fight in 85%. Ocular trauma was unilateral in 109 patients, and bilateral in 51 patients. We observed a complete disorganisation of the eye in 8 eyes, intraocular foreign bodies in 71 eyes, intraorbital foreign bodies without ocular lacerations in 23 eyes, and blunt trauma in 108 eyes. Final vision is poor or absent in 31 eyes. PMID- 8364750 TI - [Role of neutralizing antibodies in protection of the fetal from an HIV positive mother]. AB - The goal of this study is to compare serum Titers of Neutralizing antibodies in HIV 1 infected mothers to the virological status of their newborns. 38 infant mothers couples were tested. Serum Neutralizing antibodies Titers of the mothers were tested the day of birth. Virological status of new borns was determined by peripheric blood mononuclear cells culture and PCR. 18 Newborns were HIV 1 infected. In 9 cases mothers had no neutralizing antibodies: 7 newborns were HIV 1 infected. In 4 cases mothers had high level of neutralizing antibodies (< 640): none of the newborns was infected. In 25 cases mothers had intermediate value of neutralizing antibodies (between 80 and 320): 11 newborns were HIV 1 infected. Women with neutralizing antibodies to HIV 1, were less likely to transmit HIV 1 to their infants than pregnant women without neutralizing antibodies. Serum neutralizing antibodies titers of pregnant women might be of predictive value in vertical transmission of HIV 1. Further investigations are needed. PMID- 8364751 TI - [Report of activity for 1991 and 1992 of the Terminology Group (Commission no. XIV--French)]. PMID- 8364752 TI - [Surgery of carotid stenosis and prevention of cerebral infarction]. AB - In 1983, the author, relating his personal experience, as well as those of other authors, presented a critical analysis of indications and results of surgical treatment for carotid artery stenosis in order to prevent stroke. The actual experience of the author is based on for 142 patients operated on from 1st January 1982 to 31st December 1986. This study includes 32 stage 0 (asymptomatic) patients, 95 stage I (transient) patients, and 15 stage IIIa (slight deficit) patients. The immediate mortality rate has been 2.1% with a rate of severe morbidity of 1.4%. The 5 year survival rate has been 72.3% decreasing fairly regularly from 90% for the first year. The conclusions of this study and other published at the same time in the literature were that there was a category of high-risk patients with over 70% stenosis, especially those with an history of transient ischemic attack. But unfortunately no randomized work was available for supporting these conclusions. Lately, two randomized studies have been published, the first one in Europe called ECST (European Carotid Surgery Trial), and the second one in North America called NASCET (North American Symptomatic Endarterectomy Trial). The European Trial based on 2,518 patients showed that for 778 patients with a carotid stenosis between 70% and 99% and a history of a transient ischemic attack the cumulative risk of any ipsilateral stroke at 3 years was 10.3% for the surgical group and 16.8% for the medical group. The North American Trial is still more accurate. For 659 patients in the same conditions, the risk of any ipsilateral stroke at 2 years is 9% for the surgical group and 26% for the medical group. Those two studies make clear that carotid endarterectomy significatively lowers the risk of severe or lethal cerebral stroke in the patient group with a stenosis of ICA higher than 70% and a TIA. Nevertheless, there is no modification of the total mortality, of whose the first cause is coronary disease. Other studies are in progress in order to appreciate the results of surgery for stenosis between 30% and 69% and for asymptomatic patients. PMID- 8364753 TI - ["Idiopathic" extracapillary glomerulonephritides without immune deposits are vascularitides: clinical and serologic analysis]. AB - To determine the spectrum of systemic diseases potentially associated with pauci immune rapidly progressive glomerulonephritis (GN), most of which being considered as idiopathic, we have analyzed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of ANCAs in 40 patients selected only on histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24 of them. Extra-glomerular vasculitis was evidenced in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis (WG), three had a macroscopic form of polyarteritis nodosa and 17 had a clinical presentation compatible with the so-called microscopic polyarteritis previously described in the british literature. An additional patient had clinical signs of WG without clinical and histological evidence of vasculitis. ANCAs were detected in 28/33 and 25/34 sera tested by IF and ELISA, respectively: 19 contained anti myeloperoxidase (MPO) antibodies and 6 had anti-proteinase 3 (Pr3) activity. Anti MPO and anti-Pr3 antibodies were present in all clinical subgroups but with various incidences: anti-MPO antibodies were surprisingly more often detected (6/12) than anti-Pr3 (4/12) in patients with suspected or histologically proven WG but anti-Pr3 antibodies were nonetheless 3- to 4-fold more frequent in WG than in non-WG systemic vasculitis (1/12) and necrotizing CGN without evidence of extra-renal vasculitis (1/10). These results strongly suggest that pauci-immune necrotizing CGNs belong to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This hypothesis is also supported by the good response of patients to immunosuppressive treatments known for their efficacy in vasculitides, whereas these treatments are usually less successful in severe forms of extra-capillary GN with immune deposits. PMID- 8364754 TI - [Arrhythmogenic right ventricular dysplasia. A new clinical entity]. AB - Arrhythmogenic right ventricular dysplasia has been identified in 1977. It affects the right ventricle and its etiology is unknown. It has been recently included in the group of cardiomyopathies since it affects mainly the right ventricular muscle. It is found in young adults, frequently sportsmen who have a nearly normal cardiac physical examination. Ventricular arrhythmias could lead to palpitations, syncopes or even sudden death. This accident could be the first presenting sign of the disease. Two physiopathogenic mechanisms have been considered: heredo-familial origin or the result of a burned out myocarditis which could be the result of an abnormal immunological response. Its treatment mainly involves antiarrhythmic drugs. In the resistant cases ablative techniques, implantable defibrillator or surgery and even cardiac transplantation could be considered. Correctly treated, ARVD has a good prognosis. More extensive studies are necessary both on the clinical as well as the basic science standpoints. PMID- 8364755 TI - [Comparative enantioselectivity of the disposition of two non-steroidal anti inflammatory agents, ketoprofen and carprofen, in man and animals]. AB - After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant in dogs, cats and horses, with ratios of 30.3, 5.3 and 1.5, respectively, while R(-) is the predominant enantiomer in sheep. The interpretation of these inter-species differences can be supported by experimental evidence, however some informations are lacking and additional investigation is required. In the case of ketoprofen where S(+) is predominant in rats, dogs and horses, the metabolic chiral inversion from R(-) to S(+), which has been demonstrated in rats, may also take place in the latter two species. In addition, the well documented stereoselective clearance of the glucuronides, possibly in favour of the enantiomer S(+), may explain the lower body clearance of the R(-) enantiomer in sheep. For carprofen, no metabolic chiral inversion was shown in rats and dogs after administration of each enantiomer individually, but for this compound, stereoselective clearance of glucuronides has been demonstrated which may support the idea of a plasma concentration shift of the enantiomeric proportions vs time in favour of the R(-) enantiomer. Regardless of the possible biological mechanisms which are responsible for these inter-species differences, the existence of these differences gives rise to at least two important issues: The choice of animal species which can be used in the research of drugs destined for human therapeutics: the most pertinent animal species will be the one which demonstrates an enantiomeric plasma profile closest to that observed in man. The present data show that the ideal animal species from this respect has still to be identified. For application in veterinary therapeutics, a careful balance must be established between the requirement of favourable bioavailability of the active S(+) enantiomer and the potential of any possible chiral inversion of R(-) to generate hybrid molecules in meat and milk which in turn may lead to residues, the toxicity of which to the human consumer is still unknown. PMID- 8364756 TI - [Hereditary protein lithiasis and calcium lithiasis: two different forms of hereditary pancreatitis]. AB - We previously reported that the most frequent cases of chronic pancreatitis were the consequence of pancreatic lithiasis and that there were different forms of pancreatic lithiasis with different etiologies and composition of calculi. The most frequent form is the calcic lithiasis, generally due to nutritional disorders. The second most frequent form is proteic lithiasis. In this paper, we report 1.) Ten hereditary cases on a total of 36 patients presenting with proteic lithiasis (age at clinical onset 15 +/- 12 years); 2.) one hereditary case on a total of 150 patients with proteic lithiasis. In these two different maladies, the transmission seems to be dominant, autosomal with incomplete penetrance. Hereditary pancreatitis is therefore a group of at least two different diseases, hereditary protein lithiasis, the most frequent one and hereditary calcic lithiasis exceptional. PMID- 8364757 TI - [Pathologic features of a case of systemic brucellosis due to Brucella melitensis biovar 3 in a chamois (Rupicapra rupicapra)]. AB - A case of systemic brucellosis caused by Brucella melitensis biovar 3 was identified in a chamois (Rupicapra rupicapra) in the southern French Alps. Clinical signs included bilateral orchiepididymitis and keratoconjunctivitis, polyarthritis, and neurological signs; pathological findings confirmed an ulcerative keratitis, orchiepididymitis with calcified or necrotic foci and serofibrinous and hemorrhagic polyarthritis. The kidney cortex showed calcified nodules and infarctions. A small focus of chronic pleuritis was also observed. Brain and pia mater showed degeneration, necrosis and calcification with perivascular lymphoplasmacytic and granulomatous inflammation. B. melitensis was evidenced in all these organs. This systemic brucellosis is unusual in our developed countries, in human an early medical action restricts the illness to localised lesions; domestic ruminants are slaughtered at the first clinical suspicion like abortion and/or after seroconversion. PMID- 8364758 TI - [Justification and imperatives of the campaign against excess cholesterol and prevention of atherosclerosis]. AB - Recently, violent attacks have been orchestrated, by various media and the press against medical action, via diet or drug therapy, on excess cholesterol, in order to improve primary or secondary cardiovascular prevention. The amplitude of this campaign implies a dangerous risk of a deleterious effects both on the public and on medical guidelines. The opportunity for open discussion of this question, and of a clear reply, appears to be highly desirable for all concerned. Although it is quite true that total blood cholesterol levels in excess of 200 mg/dl (5.2 mmol/l) are not automatically dangerous, they nonetheless require complete profiling of cholesterol distribution among the different fractions and, if possible, a complementary study of ApoB, ApoA1 and Lpa fractions. It must be recalled that even modest rises in total cholesterol (250 +/- 30 mgs/dl) can be atherogenic, and particularly, when present in the non-HDL fractions, and involving a low HDL Cholesterol level (< 36 mg/dl or 0.9 mmol/l). In all these cases, the associated determination of triglyceride levels is absolutely necessary. Moreover these modest rises in cholesterol have to take into account the possible association of other risk factors, such as hypertension, cigarette smoking, diabetes, obesity and ... hyperfibrinogemia. The claims of the natural protection of French people against atherosclerosis and of the irrelevance of precocious cholesterol screening, then finally of non-demonstrated benefits of such prevention, with respect to other risks due to diet or drug treatment of cholesterol disorders must be precisely rediscussed and clarified. The crucial importance of the maintenance of our present efforts in cardiovascular prevention for clinicians, concerned patients, and the general public, must be especially stressed. PMID- 8364759 TI - [Teratogenesis and autoimmunity: significance of an experimental murine model for human pathology]. AB - Fetal malformations constitute a major problem of public health. Unfortunately the known causes do not account for more than 50% of the cases observed. The potential role of immune mechanisms is suggested by experimental studies in the rat indicating that antibodies reactive with the yolk sac induce fetal malformations. In this study we show that these antibodies are specific for a 280 kDa protein expressed only in the kidney and the yolk sac by cell structures associated with the formation of endocytic vesicles. We further show that a similar protein is expressed in man by the yolk sac, the kidney and the trophoblasts. The possible role in pathology of antibodies against the human protein is discussed. PMID- 8364760 TI - [Monoxycarbogenic reaction of chloral: application to the obtention of carboxyhemoglobin and to its determination in blood]. AB - Carbon monoxide CO, generated from chloral (10(-2) M) in a dilution of hemochrome (pH 13), turns the solution of hemochrome into a solution of carboxyhemoglobin. The spectrum of this solution is identical to the one obtained after bubbling with CO. The reaction is fast and makes it possible to determine the percentage of carboxyhemoglobinemia in whole blood. PMID- 8364761 TI - [Inhibition of phospholipase A2 of peritoneal macrophages in rats by 1,2-di-O hexadecyl-rac-glycero-3-phosphocholine]. AB - The 1-O-stearoyl-2-O-[3H] arachidonyl-sn-glycero-3-phosphocholine, introduced in the culture medium, was taken up by the peritoneal macrophages activated by the ionophore A 23187. After intracellular phospholipase A2 activity, the [3H] arachidonic acid was found in cells and in extracellular fluids. It also reached the eicosanoid synthesis. When it was introduced in the culture medium with the tritiated phospholipid, the 1, 2 di-O-hexadecyl-rac-glycero-3-phosphocholine, which has a non hydrolysable alkylated structure in the 2 position of the glycerol, inhibited the intracellular phospholipase A2, then contributed to lower the eicosanoid synthesis. PMID- 8364762 TI - Confirmation of the taxonomic position of Callimico goeldi (Primates, Platyrrhini) on the basis of its highly repeated DNA patterns. AB - The systematic position of Callimico goeldi has been analyzed by comparison of its highly repeated DNA fragments with those of three species of Callithricidae and two species of Cebidae. Our data, in agreement with those obtained by other authors by means of cytogenetic and molecular biology techniques, are in favour of the classification of C. goeldi in the family Callithricidae. PMID- 8364764 TI - [Ultrastructural analysis of the optic nerve in microphthalmic rodents (Spalax leucodon)]. AB - The optic nerve of a microphthalmic subterranean rodent, Spalax leucodon, has been examined at the ultrastructural level. The analysis of the optic nerve reveals only 1,790 unmyelinated axons. The axon diameter varies from 0.05 to 2.3 microns, with a mean of 0.55 micron. We suggest that these axons mainly belong to the W type ganglion cells. PMID- 8364763 TI - [Presence of gregarine (Protozoa sporozoa) parasite of black-lipped pearl oysters Pinctada margaritifera (L.,1758) (Mollusca bivalvia) in French Polynesia]. AB - High death rates have been recorded in populations of Pinctada margaritifera (natural or reared stocks) in atolls in the Tuamotu Archipelago (French Polynesia). An histological study of the oysters from the concerned areas revealed the occurrence of a protist of which ultrastructural features correspond to those of Gregarinea. It is still premature to establish a link between the presence of the Gregarine and recent deaths of pearl oysters. PMID- 8364765 TI - [Effects of NGF on chromaffin adrenaline-containing cells of adrenal medulla of rabbits transplanted into brains of mice]. AB - The graft of chromaffin adrenaline-containing (A) cells of rabbit adrenal medulla implanted to mouse brain and treated with NGF contains more survived cells 1 month after grafting than adrenal medulla alone. The cells developed either an intermediate (e.g. chromaffin cell and neuron) or a neuron-like phenotypes accompanied with a decrease in an immunoreactivity for PNMT (phenyletanolamine-N methyltransferase). A gap junctions and attached plaques were found between grafted cells. The grafts received a synaptic input. The NGF influence on the fate of chromaffin A-containing cells is discussed. PMID- 8364766 TI - [Quadri-dimensional analysis of the electroencephalography. First application to an episode of paradoxical sleep in man]. AB - A first example of quadri-dimensional EEG analysis is presented which is characteristic of a series of ten analyses episodes of paradoxical sleep recorded in polygraphy during 5 nights' sleep in three human volunteers. A first EEG recording of wakefulness, eyes open, with visual fixation of a central point, was followed by a polygraphic night of sleep recording after habituation. The first subject was recorded during three nights; two other subjects during one night only after habituation. An EEG montage of 16 channels was quantified by spectral analysis and parametrization, after artefact rejection, for the reference sequence of wakefulness and further episodes of paradoxical sleep. After temporal and spatial interpolation algorithms, for each sequence, a series of root-mean square successive EEG maps were computed and displayed, between 0.5 to 30 Hz. Low amplitude values of locally activated areas were chosen during the wakefulness EEG sequence and provided filtering thresholds for isolating activated areas during paradoxical sleep. The first 30 maps of each episode were piled up one on top of the other, along a vertical time axis, then dynamically visualised in colors and 3D. The "trajectories of activated areas" were then displayed in a quadri-dimensional functional space (x-y: spatial map of the scalp; t: time; color or black and white: filtered or unfiltered rms EEG amplitudes). The EEG trajectories of awakened areas, appeared through time like unique "fibres" or double fibres after bifurcation. The unique fibres were located over left temporo central activated areas and a double fibre appeared after bifurcation over the right parietal area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364767 TI - Brain tumors. AB - At the same time that studies indicate an increase in the frequency of brain tumors, improvements in diagnosis and treatment have increased the clinician's ability to deal with these cancers. Dr. Posner, Chairman of the Department of Neurology at Memorial Sloan-Kettering Cancer Center in New York City, encourages physicians to be alert for symptoms of brain tumors, to be positive about treatment, and to be prepared to refer patients to investigative treatment so that progress can continue. PMID- 8364768 TI - Brain tumors. AB - Brain tumors are a relatively common cancer in all age groups, and the incidence of both primary and metastatic brain tumors is increasing. Fortunately, dramatic advances in methods of diagnosis, surgical technique, and adjuvant therapy have all contributed to an improved outlook for patients with brain tumors. This article reviews the classification, symptoms, diagnosis, and treatment of brain tumors. PMID- 8364769 TI - Pediatric brain tumors. AB - Brain tumors are the second most common cancer of children. Although children with brain tumors have a better prognosis than adults, treatment presents special problems, including possible damage to the developing brain. This article reviews the classification, symptoms, diagnosis, and treatment of pediatric brain tumors. PMID- 8364770 TI - Questionable methods of cancer management: 'nutritional' therapies. AB - Although dietary measures may be helpful in preventing certain cancers, there is no scientific evidence that any nutritionally related regimen is appropriate as a primary treatment for cancer. This paper focuses on seven questionable modalities: vitamin C, pau d'arco tea, the Gerson diet, Hoxsey herbal therapy, the macrobiotic diet, Manner metabolic therapy, and Kelley metabolic therapy. Some of these approaches involve a diet that is nutritionally inadequate. Some involve potentially toxic doses of vitamins and/or other substances. Some are quite expensive. All pose the risk that patients who use them will abandon effective treatment. The American Cancer Society therefore recommends that "nutritional cancer cures" be avoided. PMID- 8364771 TI - Clinical documentation of inflammation markers in asthma. PMID- 8364772 TI - Serum measurements of eosinophil cationic protein (ECP) in bronchial asthma. PMID- 8364773 TI - Clinical experience with the measurement of ECP: usefulness in the management of children with asthma. PMID- 8364774 TI - Canadian Cardiovascular Society Annual Meeting. Vancouver, British Columbia, October 27-30, 1993. Abstracts. PMID- 8364775 TI - Analysis of factors related to treatment and prognosis of leprosy patients in southern Taiwan. AB - This study was undertaken to investigate certain factors of leprosy, using bacterial indices, disability and regular treatment as outcome variables. One hundred and fifty seven leprosy patients were interviewed, face to face personally, using a standard questionnaire, and examined in order to grade these disabilities. Their clinic charts were reviewed and summarized. Percentage, Chi square test, Fisher's exact test and logistic regression were used to analyze the data. Most patients (88%) were of low educational level; 57% were regularly treated in 1985. About half of the patients were diagnosed within one year. Dapsone was used at first diagnosis, while multiple drug therapy was in present use. The mean correct answer rate of the knowledge of leprosy was 0.49. Interaction with family members was not unusual. The major reason for neglecting treatment of the disease was that "the time is not available". Many patients did not appreciate the severity of the disease. Univariate analysis found that both "drug usage at first diagnosis" and "current drug usage" were related to "bacterial index". Only one factor "time-to-diagnosis" was related to "disability". The factors related to "regular treatment" were the "the time is not available", and "religion". Multiple logistic regression analysis found that the results were the same as those in univariate analysis, except that two more significant continuous variables were also related to regularity of treatment: duration of disease and a score of "beliefs about leprosy", neither analyzed in univariate analysis. PMID- 8364776 TI - Colloidal bismuth subcitrate, ranitidine, and ranitidine plus metronidazole in the treatment of duodenal ulcer and Helicobacter pylori infection: a controlled and prospective study. AB - A controlled, prospective clinical trial of colloidal bismuth subcitrate (CBS), ranitidine and ranitidine plus metronidazole for the treatment of duodenal ulcer (DU) is reported here, with evaluation of the possible pathogenic role of Helicobacter pylori (HP) on DU in a six-month follow-up. A total of 42 patients with active DU on endoscopy were randomly selected to receive oral CBS (300 mg 1 hour before each meal, and at bedtime, n = 16), ranitidine (150 mg bid; n = 12) or ranitidine (150mg b.i.d.) plus metronidazole (250 mg t.i.d; n = 14) treatment for one month. Ulcer healing was endoscopically evaluated. Healed patients received another two-week treatment; unhealed subjects received another one-month treatment with the same agents. Healed patients were followed endoscopically at 1, 3, and 6 months after the cessation of medication without maintenance therapy. Unhealed or relapsed subjects were excluded. To assess HP status, during each endoscopy two prepyloric mucosal biopsies were taken for urease testing and culture of HP. The prevalence of HP in patients with DU was 95.2%. Data showed that those treated with CBS had a lower DU healing rate than those treated with ranitidine or ranitidine plus metronidazole after the one-month treatment, but there was no statistical significance in the DU healing rates after the two-month treatment, and at follow-up six months after the cessation of medication. After one month of treatment those treated by CBS showed the highest rates of HP clearance on gastric antral mucosa among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364777 TI - Staging of bladder cancer by transabdominal real-time ultrasound. AB - In the past six years, there were 726 cases of proved bladder cancer in our hospital. Among these, 376 cases received transabdominal ultrasonographic examination of the urinary bladder for evaluation of the bladder tumor. Two hundred and fourteen cases of them were newly diagnosed as bladder cancer and had adequate pathological specimens for staging of the tumor. The retrospective comparison between preoperative local staging of the bladder tumor by ultrasound and final pathological report showed 78.5% of total accuracy, 9.8% of overstaging, and 11.7% of understaging. The accuracy is 87% for stage A tumor; 60.5% for stage B; 41.2% for stage C; 83.3% for stage D. Strong echogenic foci on the surface or in the tumor were detected in 39.3% (84/214) of cases, which may indicate encrusted stones on the surface of the tumor or intratumoral dystrophic calcification. There was no strong correlation between tumor grading and staging, except that most of the grade I lesions were at stage A (30/31, 97%). The preoperative local staging of urinary bladder cancer by real-time ultrasound might be of great value to determine the management planning and prognosis of the patients. PMID- 8364778 TI - Dilatation of the biliary tract in pediatric patients. AB - Forty cases of dilatation of the biliary tract in infants and children were diagnosed and treated at the Veterans General Hospital, Taipei and Taichung between 1980 and 1992. The male to female ratio was 1:2.6 and the age ranged from 1 day to 14 years. Major clinical presentations were abdominal pain (57.5%), jaundice (42.5%), vomiting (37.5%) and abdominal mass (30%); the classical triad of abdominal pain, jaundice and abdominal mass occurred in only three cases (7.5%). Abnormal liver function tests included elevated bilirubin (Bil) (22/37), aminotransferase (30/40), alkaline phosphatase (Alk-P) (34/37), lactic dehydrogenase (LDH) (22/34) and gamma-glutamyl transpeptidase (GGT) (13/15). The amylase in bile was detected in 16 cases with 10 cases higher than 500 Somogyi units/dL. All cases were diagnosed correctly, using real time sonography. Technetium-labeled scintiscan (Tc-99m DISIDA scan) was interpreted correctly in 88% (15/17) and abdominal computerized tomography (CT) in 10 cases (10/10). According to Todani's classification, type I cyst was the most common (35 cases, 87.5%) and the remaining cases were type IV-A (3 cases) and type V (2 cases). Operation was performed in 38 cases except for two who had type V dilatation of biliary tract (Caroli's disease). Complications included rupture of the gall bladder in two patients and common bile duct stone in one; mortality after operation occurred in one case. Surgical specimens of the liver revealed periportal fibrosis in nine instances. PMID- 8364779 TI - [Effect of implantation of an Ommaya reservoir on prognosis for cryptococcal meningitis]. AB - Cryptococcal meningitis has a high mortality rate of central nervous infection. The patients usually die of the disease itself, or complications from increased intracranial pressure. Early diagnosis and treatment, including surgical drainage, will improve the results. In this series, twenty-one patients with high intracranial pressure (ICP > 300 mmH2 O) are presented. Fourteen received implantation of Ommaya reservoir to aspirate cerebrospinal fluid (CSF) for relief of symptoms of ICP. Meanwhile 4 of these 14 patients also received intraventricular injection of amphotericin B because of poor response to systemic drugs. Another seven patient received systemic drug therapy only. Survival during therapy occurred in 11 of 14 patients in the surgical group, compared with only 1 of 7 patients treated by drug therapy alone (P = 0.019). In the 14 patients who received implantation of an Ommaya reservoir, there was one complication of CSF leakage when the reservoir ruptured because of repeated aspiration. For patients with cryptococcal meningitis with high ICP, early implantation of an Ommaya reservoir will improve the survival rate. PMID- 8364780 TI - [Efficacy of disodium cromolyn in adult chronic asthma]. AB - Disodium cromolyn is effective in preventing asthma, but its steroid sparing effect remains controversial. In this prospective cross-over study, we used two different brands of disodium cromolyn, Intal and Ticromil, each for 4 weeks on 7 adult patients with chronic asthma. The dosage was 20 mg qid via a special inhaler. The whole course of the study was 12 weeks for each patient, including 2 run-in weeks and 2 wash-out weeks. Patients were followed up by the same physician at outpatient clinics every 2 weeks to measure FEV1, FVC, peak expiratory flow rate (PEFR), and reversibility after bronchodilator. The physician also assessed the severity of the patients' symptoms via a special score system. Patients recorded symptom severity and frequency of medications at home on daily diary cards. Patients also measured PEFR twice a day. At the end of the treatment, FEV1 was improved more in Intal group; daily prednisolone dosage was markedly reduced in Ticromil group; PEFR was improved in both group; but neither symptom severity nor airway reversibility was significantly changed. When two groups were calculated as a whole, PEFR increased significantly from 294 +/- 20 l/min to 342 +/- 19 l/min (p = 0.0225). The daily prednisolone dosage reduced from 5.87 +/- 0.91 mg to 3.91 +/- 0.60 mg in the 3rd week and to 4.05 +/- 0.63 mg in the 4th week. The differences between these 2 dosages and the baseline dosage were statistically significant (both p < 0.05). Side effects were minimal in all patients. We concluded that after the use of disodium cromolyn for 4 weeks, PEFR was markedly improved and daily prednisolone dosage was also significantly reduced. PMID- 8364781 TI - Congenital tracheal stenosis: a report of two cases. AB - Congenital tracheal stenosis (CTS) is a rare, potentially lethal condition. Two cases were diagnosed in this hospital between 1986 and 1992. Diagnosis was confirmed by endoscopy and radiography. These two cases were noted to have symptoms of airway obstruction after an infectious process. Their outcomes were quite different. The first patient, a victim of CTS diagnosed at two years old, still lives well and has been asymptomatic for subsequent six years, though he has received no surgical intervention. The second patient, a three-month-old female, exhibited an exacerbation after bronchoscopy and died in spite of intensive care. Prompt recognition of symptoms and a thorough evaluation of airway, as well as other anomalies, is essential for proper management of children with CTS. The diagnostic modalities, management and risk factors are discussed. PMID- 8364782 TI - Malignant peritoneal mesothelioma: a case report. AB - Malignant peritoneal mesothelioma is a rare disease, not previously reported in Taiwan. The reported case concerns a 64-year-old veteran who had suffered from abdominal pain and distension for several days. After exploratory laparotomy, segmental resection of the small intestine, excised a mesenteric mass. A characteristic biphasic pattern resulting from the admixture of gland-like area and a sarcomatous stroma presented in the histologic section. A series of histochemical, immunohistochemical and ultrastructural studies proved this to be a malignant peritoneal mesothelioma. The patient died after a course of post operative chemotherapy. History of asbestos exposure, with which the tumor is usually intimately associated, could not be traced with certainty. Poor prognosis is the rule of the disease; almost all patients die within two years of diagnosis. An effective therapeutic modality is still unavailable. Here the clinical and pathologic characteristics of the tumor are described, with a brief review and discussion of the pathogenesis as well as the obscured therapeutic problem. PMID- 8364783 TI - [Combined pregnancy: a case report and literature review]. AB - Combined or heterotopic pregnancy has been regarded as extremely rare in the past three decades. If it continues without diagnosis, a life-threatening situation may occur. A case of eight-week gestation is presented in which there was threatened abortion. The patient underwent exploratory laparotomy for internal bleeding. Upon operation, combined pregnancy, with a ruptured ectopic pregnancy, was diagnosed. Left salpingectomy was performed uneventfully. Neither chronic salpingitis nor administration of ovulation-induction agents was part of past history. A viable ongoing intrauterine pregnancy continued after operation, and a normal male was delivered by cesarean section after a 39-week gestation where labor progressed too slowly for normal delivery. PMID- 8364784 TI - [Infected common iliac aneurysm due to Salmonella: a case report]. AB - A 62-year-old male, presenting with chills and fever and RLQ abdominal pain, was found to have an infected aneurysm of the right common iliac artery infected by Salmonella group C1. CT scan of abdomen and arteriography definitely identified the lesions. Antibiotic treatment and surgical intervention with aneurysmectomy and suprapubic crossover femoro-femoral artery graft resulted in a good recovery and outcome. PMID- 8364785 TI - Evaluation of the potential role of enzyme-linked immunosorbent assay in serodiagnosis of tuberculosis. AB - The serodiagnosis of tuberculosis was evaluated by means of enzyme-linked immunosorbent assay of IgG antibody to mycobacterial antigen 60. The study population consisted of 63 patients with active tuberculosis comprising 43 pulmonary tuberculosis, 15 tuberculosis pleurisy, four miliary tuberculosis, and one tuberculous lymphadenitis. The control group consisted of 48 patients embracing 8 cases of inactive pulmonary tuberculosis, 31 cases of pulmonary disorders other than tuberculosis, and nine normal persons. There was a significant difference in antibody titers of sera between patients of active tuberculosis and control group (P < 0.001). The sensitivity of the test for active pulmonary tuberculosis was 81.4% and the specificity was 85.4% (cutoff value 300 units). The sensitivity for all active tuberculosis was 61.9%. There was positive correlation between serum titer of active pulmonary tuberculosis and the extent of disease on chest radiography (r = 0.4, P < 0.01). A positive correlation was found between the titers of pleural fluids, and the corresponding sera in 15 patients (eleven tuberculous pleurisy and four nontuberculous controls) (r = 0.85, P < 0.001). Whether serum or pleural fluid, the positive rate of the assay for tuberculous pleurisy was relatively low. In conclusion, the A60 IgG ELISA test may be useful in serodiagnosis of pulmonary tuberculosis and assessment of the disease extent, although it might not yield a high sensitivity for tuberculous pleurisy. PMID- 8364786 TI - Intraocular hemorrhage and mimicking lesions: role of gradient-echo and contrast enhanced MRI. AB - Intraocular hemorrhage and mimicking lesions on precontrast spin-echo magnetic resonance images were examined with contrast material and/or gradient-echo pulse sequence. Twenty-two melanomas, nine retinoblastomas, four hemorrhages, one metastasis, and one toxocara endophthalmitis were examined. With contrast material, all tumors demonstrated enhancement, whereas hemorrhage did not. Retinoblastomas demonstrated a heterogeneous enhancement pattern. Computed tomography demonstrated corresponding intratumoral calcifications at the areas of no enhancement. Gradient-echo images demonstrated a heterogeneous pattern in the majority of the lesions compared to spin-echo images. However, relatively characteristic small round areas of signal drop-off representing calcification were observed in about half of the retinoblastomas. PMID- 8364787 TI - Distribution of joint effusion in patients with traumatic knee joint disorders: MRI assessment. AB - One hundred forty-five knee magnetic resonance imaging examinations with joint effusions were reviewed to clarify the usual distribution of joint fluids in patients with traumatic knee joint disorders. Almost all knees (99%) had effusions in the central portion, and most knees (76%) had effusions in the suprapatellar pouch. Effusions were rarely found in the posterior femoral recess (9%) or subpopliteal recess (2%). However, this difference was considered to be only a reflection of anatomic communications. Effusions were occasionally found around posterior cruciate ligaments (36%), but were less frequently seen around anterior cruciate ligaments (18%). PMID- 8364788 TI - CT manifestations of lipomas of the small intestine and colon. AB - Seven cases of lipoma of the intestine demonstrated by computed tomography (CT) are reported. There were three men and four women who ranged in age from 47 to 78 years. The lipomas were in the small intestine in four patients, and in the colon in three. CT documented the characteristic low attenuation (fat density) of these masses in all patients. It is concluded that intestinal lipomas are important indications for CT evaluations. PMID- 8364790 TI - CT and MRI manifestations of intraabdominal panniculitis. AB - We report a case of intraabdominal panniculitis. Computed tomography (CT) showed diffuse increased attenuation in the omentum, mesentery, and retroperitoneal region. As the disease progressed, the entire mesentery and retroperitoneal regions were involved. On magnetic resonance imaging (MRI), the lesion demonstrated an intermediate signal intensity on T1-weighted images and a slightly high signal intensity on T2-weighted images. Though the radiologic findings are not specific, this condition should be considered in the appropriate clinical context. PMID- 8364789 TI - Adenomyomatous hamartoma causing ileoileal intussusception in a young child. PMID- 8364792 TI - The role of computed tomography in management of patients with Crohn disease. AB - Twenty-five patients with Crohn disease were studied using computed tomography (CT). Assessment of bowel wall thickening, enlargement of the mesenteric lymph nodes, and clearness of the mesenteric vascular contour was carried out in all patients. Evidence of inflammatory reaction of the mesenteric fat was seen in 23 patients (92%) and fibrofatty proliferation was observed in seven patients (28%). Nine patients underwent surgery when symptoms and signs were severe and of long duration, while 16 patients were treated conservatively. Degree of increase in fat density, clearness of the mesenteric vascular bundles, and enlargement of the mesenteric lymph nodes were seen more frequently in the surgical group of patients. CT shows improvement of inflammatory changes after conservative therapy in some cases. A large pseudodiverticulum, pseudopolyps, and a fistula formation were also observed in some cases. CT is an important diagnostic tool in the management of patients with Crohn disease. PMID- 8364791 TI - Computed tomography evaluation of posttraumatic pulmonary pseudocysts. AB - Two cases of posttraumatic pulmonary pseudocyst are reported. The characteristic thin-walled cystic lesions with air-fluid level were demonstrated in both cases by computed tomography but in only one case by conventional chest radiography. It is predicted that more such pseudocysts would be identified by using computed tomography with patients with blunt chest trauma. PMID- 8364794 TI - Retroperitoneal leiomyosarcoma. Its MR manifestations. AB - The magnetic resonance manifestations of retroperitoneal leiomyosarcomas in two patients are described. The tumors were isointense to muscle on T1-weighted images and exhibited a relatively high signal on T2-weighted images. Postcontrast T1-weighted images after the administration of gadolinium dietilenetriaminepentaacetic acid produced moderate enhancement except in regions of central necrosis. PMID- 8364795 TI - Computed tomography of an exophytic gastric hemangioma with torsion and intratumoral hemorrhage. AB - A case of exophytic gastric hemangioma with intratumoral bleeding due to torsion of the tumor pedicle is reported. A radiograph showed a mass without phleboliths. Computed tomography (CT) demonstrated a 14-cm mass with high densities due to hemorrhage, which was contiguous to the stomach and extended to the pelvis. The tumor showed no remarkable enhancement on post-enhanced CT due to torsion of the tumor pedicle. PMID- 8364793 TI - Primary ovarian tumors in the pediatric patient: CT evaluation. AB - Primary ovarian tumors in the pediatric age group are rare with limited descriptions on computed tomography (CT). We describe the CT findings in a series of nine mature cystic teratomas, one immature teratoma, two granulosa cell tumors, and one undifferentiated small cell tumor. Four mature cystic teratomas were atypical in their CT appearance. The immature teratoma was distinguished by its large, irregular, diffusely calcified solid component. The malignant tumors were large and nearly totally solid, or if multicystic, contained a large solid component. PMID- 8364796 TI - Iliac artery aneurysms. Radiographic evaluation. AB - We present seventeen cases of iliac artery aneurysm employing a variety of different imaging modalities (ultrasound, computed tomography, arteriography, magnetic resonance imaging). The utility of each of these techniques in the patient with iliac artery aneurysm is described. PMID- 8364797 TI - Diagnostic imaging update in skeletal dysplasias. AB - The mystique of bone dysplasias is gradually vanishing. A short historical overview introduces the subject of short stature. The pathogenesis and controversial classification of skeletal dysplasias are discussed and summarized in two tables; the use of different imaging modalities is laid out along the sequential diagnostic approach and review of common orthopedic complications. References to such advances in treatment as bone marrow transplantation, bone lengthening, and the encouraging positive effect of growth hormone therapy complete this updated revision. PMID- 8364798 TI - Dyspnea and chest pain in a 14-year-old boy. PMID- 8364799 TI - Highly presumptive identification of bacterial isolates associated with the recent Canada-wide mastitis epizootic as Nocardia farcinica. AB - A highly presumptive identification of Nocardia farcinica was made of 47 bacterial isolates. Fifteen isolates from Alberta, 9 from Ontario, and 2 each from New Brunswick, Newfoundland, and Nova Scotia were from clinical cases involved in the Canadian mastitis epizootic. Seventeen additional isolates from Alberta were recovered from farm milk bulk tanks from herds found to have cows involved in the epizootic. All isolates were shown by high-performance liquid chromatography to possess mycolic acids of a size consistent with the genus Nocardia. All isolates were resistant to a concentration of 5 micrograms/mL of mitomycin C. Forty-five isolates grew well and 2 showed reduced growth in the presence of 50 micrograms/mL of kanamycin acid sulfate. Forty-six isolates were resistant to 5-fluorouracil at a concentration of 20 micrograms/mL. All isolates were resistant to lysozyme. Resistance to these compounds supported the placement of the isolates in the genus Nocardia. Thirty-five isolates produced strong beta galactosidase reactions and 12 showed weak reactions. The demonstration of beta galactosidase activity further supports the identification of the isolates as nocardiae. Attempts to identify the bacteria to species by high-performance liquid chromatography of mycolic acid esters were frustrated, since two species of Nocardia were found to have indistinguishable mycolic acid patterns. The physiological and growth characteristics of the isolates were consistent with Nocardia farcinica. PMID- 8364800 TI - Potential for carboxylation-dehydroxylation of phenolic compounds by a methanogenic consortium. AB - An anaerobic consortium that carboxylated and dehydroxylated phenol to benzoate, and 2-cresol to 3-methylbenzoic acid, under methanogenic conditions was studied. Phenol induced this transformation activity. Addition of 4-hydroxypyridine or an increase in the concentration of proteose peptone to 0.5% (w/v) delayed the transformation. Phenol enhanced the rate of transformation of 2-cresol whereas 2 cresol delayed the transformation of phenol. Phenols with ortho-substitutions (chloro-, fluoro-, bromo-, hydroxyl-, amino-, or carboxyl-) were transformed to meta-substituted benzoic acids. However, meta- and para-substituted phenols (cresols, fluorophenols, and chlorophenols) were not transformed. Phenol was most rapidly metabolized, followed by catechol, 2-cresol, 2-fluorophenol, 2 aminophenol, 2-chlorophenol, 2-hydroxybenzoic acid, and 2-bromophenol. The consortium O-demethylated anisole to phenol and 2-methoxyphenol to catechol, and oxidized 2-hydroxybenzyl alcohol to 2-hydroxybenzoic acid. Aniline, 2 ethylphenol, 2-hydroxypyridine, 2-acetamidophenol, 2,6-dimethylphenol, 2 phenylphenol, and 1-naphthol were not metabolized. PMID- 8364801 TI - The 73-kb pIAA plasmid increases competitive fitness of Pseudomonas syringae subspecies savastanoi in oleander. AB - Pseudomonas syringae subsp. savastanoi causes tumors on olive and oleander by producing the plant growth regulators indoleacetic acid (IAA) and cytokinins following infection of the plant. The contribution of IAA production to the ability of P. syringae subsp. savastanoi to grow and survive in oleander leaf tissue was studied. Bacterial strains differing only with respect to IAA production were characterized. Growth and survival of wild-type and two mutant strains of P. syringae subsp. savastanoi in oleander leaf tissue were monitored by weekly colony counts and IAA plate assays. Growth rate of the three strains in culture and in planta did not differ significantly. However, the wild-type strain reached a higher population density and maintained its maximum density at least 9 weeks longer than either mutant population. An insertion mutant containing the IAA plasmid (pIAA), but incapable of IAA production, did not maintain a higher population density than a strain cured of the IAA plasmid. The pIAA-cured strain maintained a higher population density when coinoculated with an IAA-producing strain than when inoculated alone. These results suggest that IAA production may contribute to the fitness of P. syringae subsp. savastanoi in oleander tissue and that the iaa operon alone may be responsible for the competitive advantage of cells harboring pIAA. PMID- 8364802 TI - Phylogenetic grouping and identification of Rhizobium isolates on the basis of random amplified polymorphic DNA profiles. AB - Through the use of a single, random 15mer as a primer, between 1 and 12 DNA amplification products were obtained per strain from a selection of 84 Rhizobium and Bradyrhizobium isolates. A principal-coordinate analysis was used to analyse the resulting amplified DNA profiles and it was possible to assign isolates to specific groupings. Within the species Rhizobium leguminosarum, the biovar phaseoli formed a distinct group from the other biovars of the species, viciae and trifolii, which grouped together. Isolates of Rhizobium meliloti and Bradyrhizobium species formed their own clear, specific groups. Although it was possible to identify individual isolates on the basis of differences in their amplified DNA profiles, there was evidence that some amplified segments were conserved among individuals at the biovar and species levels. PMID- 8364803 TI - Distribution and identification of proteolytic Bacillus spp. in paddy field soil under rice cultivation. AB - Proteolytic bacteria in paddy field soils under rice cultivation were characterized and enumerated using azocoll agar plates. Bacillus spp. were the proteolytic bacteria that were most frequently present, comprising 59% of the isolates. They were always the numerically dominant proteolytic bacteria isolated from three kinds of fertilizer treatments (yearly application of rice-straw compost and chemical fertilizer, yearly application of chemical fertilizer, and no fertilizer application) and at three different stages of rice development (vegetative growth stage, maximal tillering stage, and harvest stage). Of the 411 proteolytic bacteria isolated, 124 isolates had stronger proteolytic activity than others on the basis of gelatin liquefaction tests and most of them were Bacillus spp. (100% in 1989 and 92.4% in 1991). Bacillus subtilis and Bacillus cereus were the main bacteria of this group and Bacillus mycoides, Bacillus licheniformis, and Bacillus megaterium were also present. We conclude that these Bacillus spp. are the primary source of soil protease in these paddy fields. PMID- 8364804 TI - Opsonin-independent adherence and intracellular development of Legionella pneumophila within U-937 cells. AB - Legionella pneumophila adhered to and multiplied intracellularly in the human histiocytic lymphoma U-937 cell line. The infectious process was evaluated by viable bacterial cell colony counts and documented by transmission and scanning electron microscopy. In the absence of opsonins, wash-resistant bacterial adherence to host cells occurred within 1 h and attachment of 1 or 2 organisms per U-937 host cell involved close surface interactions at the prokaryotic and eukaryotic membranes. Intracellular multiplication of bacteria was maximal by 24 h after inoculation of cell monolayers. Release of L. pneumophila from these cells appeared as a lytic process that resulted in an increase in the numbers of microorganisms in the extracellular fluids and a concomitant decline in the number of intracellular bacteria. The course of cellular infection was completed by 72 h. The cellular and ultrastructural events of L. pneumophila adherence and uptake by U-937 cells in the absence of antibody or complement have been defined. In addition, this work further establishes the U-937 cell as a suitable model for investigating Legionella--host cell interactions. PMID- 8364805 TI - Rural health care. PMID- 8364806 TI - Sentence: education in ethics. PMID- 8364807 TI - Alternative funding plans. PMID- 8364808 TI - More on physician location. PMID- 8364809 TI - More on physician location. PMID- 8364810 TI - Growth of self-help movement. PMID- 8364811 TI - Skin lesions not limited to AIDS. PMID- 8364812 TI - Cardiac arrest in your community: are there weak links in the chain of survival? PMID- 8364813 TI - Cancer trends and health care. PMID- 8364815 TI - The new American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care: presented by the Emergency Cardiac Care Subcommittee of the Heart and Stroke Foundation of Canada. AB - CPR courses (both basic and advanced) continue to evolve. The recent CPR and ECC guidelines by the AHA consolidate the research and vast experience in one document. These guidelines are helpful to lay people and health care professionals who intervene in cases of cardiac arrest. They are also excellent resources for those involved in coordinating ECC systems in the community. PMID- 8364814 TI - Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of essential hypertension. PMID- 8364817 TI - To each according to need: a community-based approach to allocating health care resources. AB - OBJECTIVE: To develop a method of allocating publicly funded health care resources among communities according to their relative levels of need for health care independent of their current patterns of use. DESIGN: For each health care program population mean levels of resource allocation were calculated and were adjusted for age and sex to produce a national age- and sex-adjusted share of program resources. Indices of relative need for health care (for most programs the standardized mortality ratio) were derived from existing data on aspects of illness and death and were then used to weight the age- and sex-adjusted shares for between-community differences in health risks and health care needs. SETTING: The populations of the 49 counties in Ontario were used as the communities among which resources were allocated. Health care expenditures in 1988-89 by the Ontario Ministry of Health were used as the "budget." MAIN RESULTS: Age- and sex adjusted resource allocations weighted for between-community differences in health care needs differed from allocations based on population size, in certain cases by up to 100%. CONCLUSION: Existing data can be used to propose allocations of health care resources that relate to relative levels of need for care across communities. PMID- 8364816 TI - Nonsteroidal anti-inflammatory drugs for the prevention of colon cancer. AB - OBJECTIVE: To summarize the results of animal and human studies of the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on neoplastic growth in the colon and to outline the possible mechanisms involved. DATA SOURCES: Research articles published in English before June 1992 were identified from MEDLINE. STUDY SELECTION: Nine articles on the polyp-cancer sequence were reviewed, 8 on the apparent pathophysiologic aspects of tumour inhibition by NSAIDs and 22 on animal and human research into the effect of NSAIDs on colon carcinogenesis. RESULTS: The results of animal and human research into the anticarcinogenic effect of NSAIDs suggest that the drugs are effective in preventing tumour growth in the colon. CONCLUSIONS: Intervention studies in humans are necessary to elucidate the therapeutic possibilities of NSAIDs, particularly in populations at increased risk for the development of colon cancer. PMID- 8364818 TI - Prostate cancer trends in Canada: rising incidence or increased detection? AB - OBJECTIVES: To analyse trends in the incidence and mortality rates of prostate cancer in Canada according to age distribution, temporal pattern and provincial variation; to determine any association with the rate of prostatectomy; and to determine whether any observed increase in the rate of prostate cancer was due to an increase in the detection rate. DESIGN: Descriptive epidemiologic study based on Canadian population data from 1959 to 1989 and chart review from one Canadian hospital. SETTING: The chart review was conducted at the Ottawa Civic Hospital. SUBJECTS: The data on prostate cancer trends were obtained from the Canadian population. Charts were reviewed for two groups of patients: (a) men discharged from inpatient care during 1976 and 1986-87 with prostate cancer first diagnosed in the same year and (b) men who underwent transurethral resection of the prostate (TURP) during 1976 and 1986. OUTCOME MEASURES: Incidence and mortality rates of prostate cancer, rates of prostatectomy and TURP, and correlations between them. From the hospital data, changes between 1976 and 1986-87 in distribution of cancer stages, distribution of cases detected incidentally after surgery for suspected benign prostatic hypertrophy and average number of slides analysed per gram of tissue obtained from prostatectomy. RESULTS: The epidemiologic data showed that the age-adjusted incidence rates increased by 72% overall, an increase seen in all age groups over 60 years. The mortality rates increased by 29% overall, primarily in men over 85 years old. The prostatectomy rate increased by 55%. There were significant linear correlations between the national and provincial incidence rates of prostate cancer and the TURP rates. The chart review revealed that during 1976, 53% of the cases of prostate cancer diagnosed were localized, as compared with 75% in 1986-87 (p < 0.01). The proportion of tumours diagnosed incidentally in men undergoing TURP increased by 11%, whereas the number of procedures did not increase. Significantly more slides per gram of tissue were analysed in 1986-87 than in 1976 (p < 0.01). CONCLUSIONS: The correlations between the incidence rates of prostate cancer and those of TURP suggest that increased treatment of benign prostatic disease has led to increased detection of prostate cancer. Extrapolation of the data obtained from the chart review indicates that the increase in observed incidence rates can be attributed to an increase in the rate of localized disease and thus primarily to early detection rather than to elevated risk. However, because the rate of death from prostate cancer was elevated in elderly men, increases in exposure to unestablished risk factors cannot be ruled out. PMID- 8364819 TI - Prevalence of and risk factors for sudden infant death syndrome in Canada. AB - OBJECTIVE: To analyse and describe the prevalence of sudden infant death syndrome (SIDS) in the Canadian population in relation to the distribution of known risk factors for the syndrome. To explain the observed interprovincial variation in SIDS rates. DESIGN: Retrospective population-based case-control study. SETTING: All the provinces and territories of Canada except Quebec. SUBJECTS: The birth and infant death records of singleton births for 1986-88 were linked. The linkage was successful in matching 904 (86%) of the 1053 deaths attributed to SIDS to the birth file for the infant. For each SIDS case three control babies who survived infancy were chosen at random, matched by province of birth. MAIN OUTCOME MEASURES: Infant death classified as a "sudden infant death." Independent variables included infant's sex, birth weight and gestational age, being small for gestational age, mother's age, marital status and parity, and father's age. RESULTS: The risk of SIDS was greater for boys (odds ratio [OR] 1.47, 95% confidence limits [CLs] 1.26 and 1.70) than for girls and was greater for the infants of unmarried women (OR 3.48, 95% CLs 2.94 and 4.11) than for those of married women. The risk of SIDS was inversely related to birth weight (p < 0.001), duration of pregnancy (p < 0.001) and mother's age (up to age 35) (p < 0.001) and was directly related to parity (up to four) (p < 0.001). The available information on birth and death registrations enabled about 30% of deaths from SIDS to be predicted. CONCLUSIONS: Logistic regression equations based on the risk factors available in vital statistics data have low power to predict provincial differences in rates of SIDS. Consequently, there may be additional factors that may explain provincial variation. There is a need for a well designed case-control study that examines more variables than are available through vital registration systems. PMID- 8364820 TI - No prescription for despair. PMID- 8364821 TI - Statement on influenza vaccination for the 1993-94 season. The National Advisory Committee on Immunization. PMID- 8364822 TI - Life after Nancy B. PMID- 8364823 TI - British nurse gets life sentence after conviction for work-related murders. PMID- 8364824 TI - MDs in newly independent Latvia struggle to learn about medical advances in West. PMID- 8364825 TI - "Second sexual revolution" creating STD crisis in Canada, doctor warns. PMID- 8364826 TI - Controlled-drinking advocates challenge use of abstinence model in treatment of addiction. PMID- 8364827 TI - Sweeping demographic changes may provide major challenges for Canada's doctors. PMID- 8364828 TI - Legislative and regulatory update: federal reimbursement revisited. PMID- 8364829 TI - Shared governance: a power shift. PMID- 8364830 TI - Development of a transcultural health education program for the Hmong. AB - CNSs face unique opportunities and challenges in meeting the health care needs of culturally diverse populations. As an education consultant involved in the development and implementation of a transcultural health education program, a CNS is required to have expert knowledge of the target population's health beliefs, values, and practices as well as knowledge of their language, level of literacy, and traditional teaching-learning styles. A critical consideration includes the use of a pluralistic model of education that addresses both the implicit and explicit conditions of learning and education. This paper describes the model and its application in the development and implementation of a health education program for the Hmong. The transcultural education process is examined and analyzed for appropriateness and effectiveness. PMID- 8364831 TI - A program for water-intoxicated patients at a state hospital. AB - During normal circumstances, individuals have a delicate balance of water requirement and water intake. If the balance of water is altered, electrolyte imbalance can occur. If fluid intake continues uncurbed, an extreme condition may result known as self-induced water intoxication and psychoses. If untreated, complications may develop, including dilated and hypotonic bowel and bladder, hydronephrosis, renal failure, congestive heart failure, mild confusion, acute delirium, seizures, coma, and death. The ongoing problem of water intoxication presents a modern day nursing challenge to psychiatric nurses. The present study monitors nine chronically ill patients in a special program for water intoxication involving control and monitoring and a psychoeducational group approach in a closed unit of a state hospital. At the end of 3 months serum electrolytes, serum osmolality, and urine specific gravity were within normal limits since the start of the program. Anxiety, as evidenced by restlessness, pacing, increased talking, demanding behavior, hyperactivity, yelling, and irritability, had lessened. This improvement was accompanied by a stabilization of psychotic behavior. The use of restraints dropped from 1303 hr in the 3 months before the program to 20 hr and 55 min for the nine patients in the first 3 months of the program. Progress in relation to the study hypothesis will be evaluated every 3 months. PMID- 8364832 TI - The role of the nurse in advanced practice in bereavement care. AB - The CNS may be instrumental in assisting patients, families, and staff in dealing effectively with loss and grief. This paper presents a review of theoretical and research literature examining theories and current research on grief. Physical and emotional responses to loss are discussed, and factors that influence the bereavement process are presented. The role of the CNS in facilitating grief resolution and in assisting the staff nurse to intervene appropriately with the bereaved is examined. PMID- 8364833 TI - Reminiscence: a viable option to enhance power in elders. AB - The purpose of this study was to investigate the usefulness of reminiscent storytelling as a therapeutic modality to enhance the sense of power in well elders (ages 60-86). The study was conceptualized within Rogers' (1986) Science of Unitary Human Beings and focused on Barrett's theory of power. A pre- and posttest design with experimental and control groups was used with Barrett's Power as Knowing Participation in Change Test, Version II as the measure of power (personal control). Experimental group subjects were pretested and then participated in three reminiscence sessions during a 1-week period. Subjects were then posttested both at the end of the reminiscence sessions and again after a 5 week interval. Control group subjects were tested on a schedule identical to that of the experimental group, but participated in no reminiscence sessions. Although an overall significant difference (p = 0.003) in scores was found over the testing period, no differences were found between experimental and control groups. Both experimental (n = 34) and control (n = 41) groups demonstrated a small but insignificant decrease in power between the pretest and posttest 1. Both groups then experienced a significant increase in power between posttest 1 and posttest 2. It is recommended that research energies continue to be directed toward the investigation of this topic. In our contemporary high tech world which often allows minimal human contact and diminishing quality of life for the aged, novel modalities such as reminiscence offer a human to human exchange, which may hold the key to this modern-day challenge. PMID- 8364834 TI - The association between CNS direct care time and total time and very low birth weight infant outcomes. AB - This study examined the association between the amount of direct care time and total time (direct and administrative) spent by CNSs with families of 39 very low birth weight infants (< or = 1500 grams) and infant outcomes (rehospitalizations and acute care visits). Documentation of the CNSs' time spent with infants and families was recorded during infant hospitalization and for 18 months after infant discharge. The number of infant rehospitalizations and acute care visits was recorded from hospital and physician records. The mean total time the CNS spent per infant for the 18-month period was 27.3 hours. After discharge, there were significant relationships between the amount of CNS direct care time and the number of acute care visits (r = 0.45, p < 0.01) and infant rehospitalizations (r = 0.51, p < 0.01). Although the study findings did not demonstrate improved infant outcomes associated with the amount of time the CNS spent with this high risk population, they document the amount of CNS time spent in intervention and follow-up of these infants. This study provides data for costing home visiting by the CNS in this patient population. PMID- 8364835 TI - Oh no, they're coming! PMID- 8364836 TI - Preparing the CNS for participation in quality assurance activities. AB - Preparation of CNSs must include advanced knowledge in the area of clinical specialty and experience in the various subroles of the clinical specialist. In order to enhance students' knowledge and skills related to these subroles, the authors instituted a clinical project focusing on quality assurance activities for students enrolled in the medical-surgical nursing major in a large graduate nursing program. Students begin the project during the clinical practicum by identifying an area in need of quality assurance monitoring. Students then develop monitoring tools, collect data, and make recommendations for changes in clinical practice. The project gives the students practical experience in an important area of clinical specialist practice and can be adapted or expanded for any clinical major. PMID- 8364837 TI - The CNS role: evolution within a shared governance environment. AB - Organizational change has a profound impact on the role of the CNS. Movement in our institution from a centralized structure to a shared governance philosophy redirected the work of the CNS. This article describes the change response spiral that reflects the CNS role evolution and activities required by the CNS to foster the change. Three phases of the response spiral are highlighted: creating a culture, restructuring, and adaptation. CNS activities and experiences associated with the change will be of interest to administrators and CNSs. PMID- 8364838 TI - Communicating the financial worth of the CNS through the use of fiscal reports. AB - To maintain the clinical nurse specialist's (CNS's) leading role within hospital nursing services, routine communication to hospital administration of the impact of the CNS role on the hospital's budget is imperative. The CNS group at Children's Hospital of The King's Daughters implemented a quarterly Fiscal Report to clarify the financial worth of CNS practice. The Fiscal Report presents cost savings and revenue generating activities utilizing the role components of the CNS. During fiscal year 1991, the CNS group reported a total impact of $1,600,000. This article describes in detail the use of the Fiscal Report. PMID- 8364839 TI - A patient-centered solution to an institution's need for information. PMID- 8364840 TI - The collaborative role of the CNS in support groups. AB - This project's purpose was to illustrate how the CNS is central to developing a support group using consultation and collaboration. Identification of patient and family needs is a growing challenge in general medicine. Otherwise left unresolved, the needs of the patient and family are addressed and met through the support group. PMID- 8364841 TI - The Bergmann Foot Scanner for automated orthotic fabrication. AB - The word automation sometimes can be misleading. I believe that some feel that automation of orthotic manufacturing results in a system in which orthotics are mass produced. Still others believe that the main reason for automation is to make orthotics quicker and cheaper and not individualized. As far as the author's laboratory is concerned, nothing could be further from the truth. We think of automation as the use of computer technology to make orthotics that are more accurate and more specialized as to the doctor's specific requirements. This is a method that takes the expertise of the podiatrist and the laboratory technician and gives them a tool that can be used to achieve the perfection in orthotic fabrication they are trying to attain. In testing out new types of cast correction designs, computer-designed images will give the repeatability needed in scientific research not found with manually applied corrections. The optical scanner has given us more than just a means of sending a cast to the laboratory quickly. It has turned out to be a method to help explain biomechanics of the patient's foot in a clear and concise way. We also have watched it develop into a research tool that podiatry schools and others can use to verify and further biomechanical principles. PMID- 8364842 TI - Computer-generated orthoses. A review. AB - It is obvious with the various casting techniques used in the study that the ease with which individuals adjust to the fashionette orthotic makes it a desirable device. It is tolerated well with higher-heeled shoes and shoes that are used more for fashion purposes. Future studies need to assess the degree of control compared with the type of deformity and the type of symptoms the patient has. These types of devices may be sufficient to minimize stress on a given deformity, such as a neuroma, but may not be sufficient enough to eliminate the need for the removal of the neuroma. Recurrence of the neuroma after it has been resected and the patient prescribed a fashionette orthosis also needs to be assessed. A neuroma is one example of a type of deformity that needs to be controlled and evaluated with regard to cause and response to orthotic therapy. Abnormal tylomas and pressure lesions need to be assessed on a symptomatic basis for their control with the different types of devices and the pathomechanic causing the pressure. This study indicates that milled orthoses are tolerated better than pressed orthoses. Milled orthoses require less adjustment and the adjustment is tolerated better, regardless of the casting position. The degree of position control had some variations. When comparing the pressed and the milled functional orthoses, there is a more rapid adjustment with the milled type of orthoses. This suggests that possibly the milled orthoses have less alteration in shape and loss of contour from the direct milling and the digitizing process compared with the pressing techniques. The long-term effect of pressing compared with milled orthotics was not assessed during this study with regard to fluid distortion of the polypropylene over time. The fluid nature has a tendency to suffer a loss of contour and progressive loss of function. The milled process theoretically has less change in the contour with the passage of time, although this needs to be assessed in further studies. Possibly, the fluid nature of the orthosis can be assessed by determining how soon the symptoms return between adjustments. Posting surfaces tend to wear over a period of time and distort with the fluid nature. The posting can break down from the type of material from which it is made. A model of assessment for future studies may be to check the duration of when heel spur types of symptoms or postural complex types of symptoms, such as knee pain or lower back pain, recur.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364843 TI - In-office computerized fabrication of custom foot supports. The AMFIT System. AB - This article familiarizes the podiatric physician with computer-aided design and manufacturing of custom orthoses in an office setting using the AMFIT System. Topics discussed include machine specifications and descriptions, data acquisition, and finishing. PMID- 8364844 TI - An overview of foot pressure measurement systems. AB - Pressure measurement systems are increasingly important for the clinician in the 1990s; however, choosing the right device is still not an easy task. This article, an overview of current technologies, focuses on the basic principles of new systems and clarifies technical specifications but does not judge specific brands. Based on long-term experience with pressure measurement systems, requirements for everyday use are made and discussed with respect to currently available technologies. For all persons who are in the process of buying a system, this article serves as a reference to help them find the most ideal system for a specific application. PMID- 8364845 TI - The PEL-38 Electronic Podometer for static and dynamic analysis of foot biomechanics. AB - The PEL-38 Podometer is a practical computer system for the analysis of foot function. Designed, tested and used at leading medical centers on the European continent, it has been introduced in the United States by Physical Support Systems (6 Ledge Road, Windham NH 03087; 1-800-222-5009). The PEL-38 Podometer measures, records, and graphically analyzes foot pressure distribution in both static and dynamic modes. PMID- 8364846 TI - The E.D.G. System for dynamic analysis of gait. AB - It is important to recognize that the value of the E.D.G. system requires a higher level of understanding of the biomechanics of the lower extremity. This is needed to correlate the information gathered from the system with the actual episodes that are accurate. In addition, it is important to remember that the acquisition of any clinical assessment instrument should be based on what information you are attempting to acquire and whether the instrument can provide it. Ask yourself, "what do I want to know, and can this instrument provide the answers?" This article has been written to acquaint the reader with a working knowledge of the E.D.G. system, the science of clinical electrodynography, and its use as a clinical tool. The addition of dynamic in-shoe data to the basic static information allowed from a patient examination adds a new dimension to clinical assessment. Clinical decision making and treatment programs can now be instituted with reasonable assurance of a favorable outcome. PMID- 8364847 TI - The EMED System of foot pressure analysis. AB - The EMED System is actually a family of individual modules developed to measure and record pressure distribution under the plantar surface of the foot to provide important information regarding the loading characteristics of the lower extremity. One must distinguish between static measurements taken while the patient is standing and dynamic measurements taken during locomotion. With static measurement, it is not possible to determine the form or the loading pattern of the foot during function. Dynamic measurements are used to determine loading during the actual stance phase of gait, quantified by parameters such as the length and width changes of the foot, angle of gait, digital function, high pressure points, and many other parameters. Important measurement parameters are calculated automatically using either EMED-Intern or EMED-Extern software. Each module of the EMED System is designed specifically to provide the clinician or investigator with the appropriate tool to collect data for analysis of function, direct therapy, and aid in the diagnosis of functional foot problems. PMID- 8364849 TI - The optical pedobarograph. AB - The optical pedobarograph has proven to be very helpful in studying foot pressure abnormalities in a variety of clinical conditions and especially in diabetes mellitus and rheumatoid arthritis. Studies using this device have provided a very good insight into the etiopathogenesis and natural history of foot disorders. It has also allowed the conduction of intervention trials which assess the efficacy of new treatment. The main advantages of the pedobarograph include accuracy, reliability and high spatial resolution. Its drawbacks are its size and that it can only measure pressures between the foot-floor interface. PMID- 8364848 TI - The F-SCAN system of foot pressure analysis. AB - The age of computerized gait analysis is here. There are several systems available to meet the needs of the podiatric practitioner. This author believes that the F-SCAN technology system makes a significant contribution to the practice of podiatric medicine. The system is user friendly, accurate, reproducible, and affordable. Its graphic display capabilities are colorfully attractive and easily understood. The primary focus of the F-SCAN system is that of peak pressure distribution over time. Vertical plantar pressure dispersion across the plantar surface of the foot is recorded, processed, and graphically displayed in terms of sequential gait changes. The system further allows for the manipulation of the accumulated data to present it in a more comprehensive manner. Future updates on the F-SCAN software are already close at hand and are expected to enhance the diagnostic capabilities of the system further. The four primary areas of clinical application for F-SCAN have been identified and briefly discussed. The recognition of certain biomechanical abnormalities, monitoring preorthotic and postorthotic use, evaluation of the diabetic or neuropathic foot, and presurgical and postsurgical functional examinations constitute this group. The F-SCAN system largely helps to remove some of the unavoidable guess work from essential diagnostic and therapeutic procedures. As we increase our understanding of the pathomechanics of these clinical problems, so too will we improve our management of the associated complications. Years ago, at the time when computerized gait analysis was being introduced to the podiatric profession, a frequently asked question was: What does it tell me that I don't already know or can't see by watching the patient walk?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364850 TI - The computer era in gait analysis. AB - This article traces the history of the use of computers in the analysis of human gait. Following a brief retrospective review of the precomputer era, the topics of motion, force, and pressure analysis using computers are discussed. The need for careful justification of clinically applied techniques is stressed throughout, and some future trends are anticipated. PMID- 8364851 TI - The Vector System for dynamic gait analysis. AB - This article explores dynamic versus static biomechanics, quantitative versus qualitative data, and practical uses in a clinical setting for the Vector System of gait analysis. This system uses a video camera connected to a computer to analyze gait. PMID- 8364852 TI - The motion analysis system for dynamic gait analysis. AB - The research value of the Motion Analysis System, within its scope of limitations, is large and may allow the podiatrist to lend scientific data to support many areas that have been previously held to be of a theoretic or anecdotal basis. The whole concept of rearfoot control with orthoses is perhaps the most important of these. Podiatrists have been aware of the role of orthoses for years, but now there is the means to demonstrate these findings to other medical professions. The ability to compare a number of clinical variables is another truly useful feature. The Motion Analysis System and other similar equipment are not designed to replace or make obsolete the biomechanical examination and "trained human eye;" rather, they act to compliment these skills and to help bring the realm of podiatric biomechanics and orthotic therapy into the scientific arena. PMID- 8364853 TI - The peak performance system for dynamic gait analysis. AB - The PEAK Rearfoot Clinical Assessment System provides automated computer tracking of tibial-calcaneal motion via video equipment. Multiple trials from a single subject or across subjects can be acquired from which angular displacements and velocities can be computed. Graphic and tabular reports can be customized to generate rapid and specific documentation. PMID- 8364854 TI - OrthoGraphics. A two-dimensional surgical planning system. AB - Presurgical planning is a useful means of attaining consistent and predictable surgical results. The range of intraoperative errors is narrowed, and surgical time and materials are minimized. Computer-assisted presurgical planning is an extremely valuable tool for reconstructive foot surgery. A versatile, self-taught software program that permits longitudinal tracking of deformities and visualization of multiple surgical options, i.e., base wedge versus neck osteotomy, is effective in terms of cost, speed, accessibility, documentation, research, and education. The concept of CAD in presurgical planning is not new to other surgical specialties, but as of this date, it has not been implemented fully by podiatric surgeons. The cost factor for office computer use has decreased significantly over the years, and it is highly unusual to locate an office today that does not employ a computer in some aspect of office operation. The additional hardware and OrthoGraphics software at this date may represent between a $6000 and $20,000 investment, depending on how sophisticated an office operation is desired. It is of particular interest that one optical disk in the ICS can hold up to 1000 patient records with nearly 4000 radiographs. In addition, a 35-mm slide-creating interface is available along with the opportunity to modify existing programs to create custom software to meet special needs. It would appear that the teaching applications of this type of system are most compatible with the podiatric medical college clinical curriculum as a component of instructional programs in both biomechanics and surgery. PMID- 8364855 TI - The application of computer graphics in foot and ankle surgical planning and reconstruction. AB - This article presents examples of current technologies in computer graphics as applied to foot and ankle surgery. Presently, there are two areas of great potential in computer graphics: (1) preoperative surgical planning, and (2) computer-aided design and manufacturing of custom implants. PMID- 8364856 TI - The use of ADAM software in podiatry. AB - ADAM (Animated Dissection of Anatomy for Medicine) software is a versatile, multimedia computer program designed to enhance doctor-patient communication. This interactive software promises to play a major role in health care in the 21st century. Podiatric applications of this software are discussed in this article. PMID- 8364857 TI - Aggressive pulmonary metastasectomy facilitated by use of median sternotomy and neodymium:yttrium-aluminum-garnet laser. PMID- 8364858 TI - Mammography screening for breast cancer. PMID- 8364859 TI - Prognostic value of DNA ploidy in squamous cell carcinoma of esophagus. Analyzed with improved flow cytometric measurement. AB - BACKGROUND: The prognostic value of flow cytometric DNA analysis on paraffin embedded tumor samples has been controversial in esophageal cancer. To clarify its true significance, the authors developed an improved method that excludes the possibility of contamination by lymphocytes in tumor sample. METHODS: Single nuclear suspension was prepared from paraffin-embedded samples on 103 patients with squamous cell carcinoma of the esophagus. Both DNA content and nuclear size were simultaneously measured by flow cytometry on 30,000 nuclei, and contaminated lymphocyte nuclei were eliminated from the data by optimal gating. Correlation between DNA ploidy and postoperative survival was examined. RESULTS: Analysis using a flow cytometric cell sorter showed that the frequency of tumor cells in the lymphocyte-reducing gating fraction (LGF) was significantly higher than that in the conventional nongating fraction (NGF). LGF analysis showed aneuploid peaks in 58 patients (56.3%), but NGF analysis showed aneuploid peaks in only 38 patients. LGF analysis revealed that the aneuploid tumors had higher histologic grading (P < 0.05) and worse survival rate (P < 0.01) compared with diploid tumors. However, conventional methods could not detect this difference. CONCLUSIONS: Flow cytometric analysis gating by nuclear size may be helpful to detect aneuploid peaks, and for predicting prognosis of patients with squamous cell carcinoma of esophagus. PMID- 8364860 TI - DNA flow cytometry of stomach cancer. Prospective correlation with clinicopathologic findings. AB - BACKGROUND: DNA ploidy and S-phase fraction measured by DNA flow cytometry were shown to correlate with several clinicopathologic characteristics in several types of tumors. METHODS: DNA flow cytometry was performed on 329 samples (164 normal mucosa, 165 tumors) obtained from 165 patients (112 men) with stomach cancer, and the findings were correlated with various clinicopathologic characteristics of the patients in a prospective manner. RESULTS: Seventy-nine of 165 samples (48%) from the tumors gave an aneuploid histogram. None of 164 samples from the normal mucosa showed aneuploidy. There was no significant difference in the frequency of DNA aneuploidy in terms of age, sex, symptom duration, bleeding history, gastric outlet obstruction, weight loss, performance status, serum hemoglobin level, albumin level, creatinine level, tumor size, tumor location in the stomach, and TNM stage. Moderately well differentiated tumors had a significantly higher frequency of aneuploidy compared to well differentiated or undifferentiated tumors. S-phase fraction was obtained in 162 of 164 samples from the normal mucosa, and 123 of 165 samples from the tumors. The overall mean of the S-phase fraction was 4.01% (range, 0.5-23.6%) for the normal mucosa and 13.8% (range, 0-51.9%) for the tumors. Higher S-phase fraction of tumors was correlated with history of weight loss, poorer performance status, and histologically less differentiated tumors. CONCLUSIONS: The overall frequency of aneuploidy was 48% in stomach cancer. DNA aneuploidy showed significant correlation with histologic differentiation of tumors. S-phase fraction of the tumors showed significant correlation with history of weight loss, performance status of the patients, and histologic differentiation of tumors. PMID- 8364861 TI - Predictive value of preoperative serum sialyl Tn antigen levels in prognosis of patients with gastric cancer. AB - BACKGROUND: Expression of sialyl Tn antigen (STN) or serum STN levels were reported to be the independent prognostic factors of colon and ovarian cancers, respectively. The clinical significance of serum STN was evaluated as a tumor marker in gastric cancer. METHODS: Preoperative STN levels were examined in 350 patients with gastric cancer, surgically treated in the Department of Surgery II, Kyushu University Hospital, and in the National Kyushu Cancer Center, between April, 1981 and April, 1986. The patients were divided into two groups: a high STN group (n = 304), with over 45 U/ml of STN, and a low STN group (n = 46), with less than or equal to 45 U/ml. RESULTS: In the high STN group, the patients were older and the tumors were larger, compared to the low STN group. Histologically, tumors in the high STN group were deeply penetrating and the rates of lymphatic involvement, vascular involvement, and lymph node and hepatic metastases were higher. Infiltrative growth patterns dominated. Thus, the tumors were in an advanced stage. The 5-year survival rate for patients in the high STN group was significantly less than that of patients in the low STN group (44.8% +/- 7.9% versus 75.1% +/- 2.6%, P < 0.05). CONCLUSIONS: Because a high STN level correlates with an advanced tumor stage and a poorer prognosis, close follow-up and aggressive therapy are recommended. PMID- 8364862 TI - The association of Helicobacter pylori with differentiated-type early gastric cancer. AB - BACKGROUND: Recent studies have indicated that infection with Helicobacter pylori is closely associated with increased risk for gastric cancer. Previous studies, however, usually have been made on cases of advanced gastric cancer. METHODS: The Congo red-methylene blue test was performed on 19 healthy subjects, 24 patients with early gastric cancer of differentiated type, and 17 patients with early cancer of undifferentiated type. H. pylori infection was examined by culture of biopsy specimens obtained from noncancerous antral mucosa. RESULTS: H. pylori was detected in 19 (79%) of 24 patients with differentiated-type early gastric cancer, but in only 5 (29%) of 17 patients with undifferentiated-type early gastric cancer; this difference was statistically significant. It also was detected significantly more frequently in patients with differentiated cancers than in healthy subjects. CONCLUSIONS: H. pylori infection was closely associated with differentiated-type gastric cancers, but not with undifferentiated types. PMID- 8364863 TI - An immunohistochemical study of ras oncoprotein expression in gastric carcinoma. AB - BACKGROUND: Previous studies have shown that ras oncoprotein is overexpressed in gastric carcinoma. It is unsettled whether there is differential expression of this oncoprotein in the two major subtypes of gastric carcinoma--intestinal type and diffuse type. METHODS: Forty-four cases of gastric carcinomas (24 intestinal type, 18 diffuse type, and 2 mixed according to the Lauren classification) were analyzed for ras oncoprotein expression using commercially available antibodies in routinely formaldehyde-fixed, paraffin-embedded tissue sections. RESULTS: Altogether, 13 cases stained unequivocally, and these appeared as granular cytoplasmic staining in tumor cells. Only five were intestinal-type carcinomas; the remaining eight were diffuse type and included two intramucosal carcinomas. When the comparison between the two subtypes was limited only to the poorly differentiated carcinomas, the difference was statistically significant (P < 0.05). ras Oncoprotein also was strongly expressed in normal duodenal mucosa as well as areas of gastric intestinal metaplasia. CONCLUSIONS: These results suggest that the strong expression of ras oncoprotein in gastric intestinal metaplasia may be merely a reflection of metaplastic change to an intestinal epithelial phenotype. The differential expression of ras oncoprotein between diffuse-type and poorly differentiated intestinal-type gastric carcinoma implies that these are two distinct subtypes of gastric carcinoma. PMID- 8364864 TI - Parathyroid hormone-related protein in gastric cancers with heterotopic ossification. AB - BACKGROUND: Parathyroid hormone-related protein (PTHrP) has been regarded as one of the substances causing humoral hypercalcemia of malignancy. METHODS: The immunohistochemical localization of PTHrP was investigated in 33 cases of gastric cancer (4 with heterotopic ossification and 29 without heterotopic ossification) to clarify the role of PTHrP in heterotopic ossification by using the anti-PTHrP monoclonal antibody, 4B3. RESULTS: The four cases with heterotopic ossification showed positive staining at primary or metastatic sites, and in one case fibroblasts in the stroma surrounding the heterotopic ossifying foci also showed positive. On the other hand, of the 29 cases without heterotopic ossification, only 5 showed positive staining. CONCLUSIONS: The presence of PTHrP in ossifying gastric carcinomas at a relatively high rate indicates that PTHrP also might be related to heterotopic ossification associated with malignancies. It is speculated that PTHrP would contribute to heterotopic ossification by facilitating the process of mineralization. PMID- 8364866 TI - Prognostic factors of malignant fibrous histiocytoma of bone. A clinical and histopathologic analysis of 34 cases. AB - BACKGROUND: Malignant fibrous histiocytoma (MFH) of bone is a rare bone tumor, and its prognosis has been controversial. METHODS: Thirty-four patients with MFH of bone were examined clinicopathologically for prognostic factors. RESULTS: The most common skeletal site of the tumor was the femur (15 cases), followed by the pelvic bones (6 cases), tibia (5 cases), and fibula (5 cases). Of 29 patients available for follow-up, the 5-year survival rate of 17 who underwent adequate surgical treatment was 63%. The 5-year survival rate of the remaining 12 patients, including 5 with MFH of the pelvic bone who received inadequate or palliative surgery, was 17%. All six patients who received intensive chemotherapy combined with adequate surgical treatment were alive and well 5 years after the initial treatment. Histologically, the presence of desmoplasia and chronic inflammatory infiltration in the tumor tended to be prognostic indicators, although not to a statistically significant extent. Patients whose tumors contained wide areas of desmoplasia had a worse prognosis (5-year survival rate, 20%). In contrast, those with a prominent chronic inflammatory infiltrate had a 5 year survival rate of 78%. CONCLUSIONS: These histologic variables would be helpful for predicting the prognosis of MFH of bone. Adjuvant intensive chemotherapy combined with adequate initial surgery may effect a clinical cure. PMID- 8364865 TI - Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples. AB - BACKGROUND: Gallbladder diseases, especially cholelithiasis, are extremely frequent in Chile, and an increasing frequency of gallbladder carcinoma has been observed during the last decades. Hyperplastic and atypical epithelial lesions of gallbladder epithelium have been considered potential precursors of invasive carcinoma. The current study was designed to study the frequency, distribution, extension, and probability of routine detection of potentially preneoplastic changes of gallbladder epithelium. METHODS: Epithelial changes were histologically studied by mapping gallbladders obtained at elective cholecystectomy for lithiasis in 162 Chilean patients. RESULTS: Antral-type metaplasia was found in 95.1% of the cases, intestinal metaplasia in 58.1%, hyperplasia in 46.9%, dysplasia in 16%, and carcinoma in situ in 2.5%. A significant association of intestinal metaplasia with hyperplasia, intestinal metaplasia with dysplasia, and hyperplasia with dysplasia was found. Hyperplasia and dysplasia were also present in four cases with carcinoma in situ. Mean extension of the lesions (percentages of the sections in which the change was observed) was antral-type metaplasia (62.7%), intestinal metaplasia (25.3%), hyperplasia (24.1%), dysplasia (15.5%), and carcinoma in situ (9.7%). Antral-type and intestinal metaplasia were more extensive and more severe in patients older than 50 years of age. Hyperplasia was more extensive in cases in which it was associated with dysplasia and carcinoma in situ. CONCLUSIONS: The extension of metaplasia seems to depend in part on the age of the patients. The association of intestinal metaplasia with hyperplasia and dysplasia agrees with the findings of other authors that relate metaplasia to gallbladder cancer. The epithelial lesions are focal or partially confluent, thus a single random histologic section will detect less than one third of the hyperplasias, dysplasias, and carcinomas in situ. PMID- 8364867 TI - Epidermotropic metastatic melanoma. Are the current histologic criteria adequate to differentiate primary from metastatic melanoma? AB - A case is reported of a patient with a lentiginous acral melanoma of the heel that was excised and recurred 3 years later at the margin of the previous scar. After another 3 years, a group of five small lesions appeared in the thigh that were considered to be junctional and epidermotropic metastases. The authors question the current histologic criteria for differentiating junctional and epidermotropic metastases of previous melanomas from multiple primary melanomas. It is concluded that the clinical history is of primary importance in reaching a correct diagnosis; histologic studies are not sufficient. PMID- 8364868 TI - Tamoxifen modulation of cisplatin resistance in patients with metastatic melanoma. A biologically important observation. AB - BACKGROUND: Treatment with the four-drug combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP), and tamoxifen (TAM) has resulted in an overall response rate of more than 50% in patients with metastatic melanoma. Deletion of TAM from the regimen resulted in a decrease in the response rate to 10%, suggesting an important role for TAM. The authors have subsequently demonstrated that TAM is highly synergistic with DDP in a human melanoma cell line, T-289, which supports the clinical observation that TAM is important in this regimen. The authors conducted a clinical trial to determine whether the addition of TAM can overcome established DDP resistance in patients with malignant melanoma. METHODS: Patients with metastatic melanoma were initially treated with DDP 100 mg/m2 alone until they demonstrated DDP resistance. On the next cycle of treatment, patients received TAM 40 mg by mouth four times a day on the day before DDP treatment followed by 20 mg by mouth daily for the rest of the 3-week cycle plus the same dose of DDP. RESULTS: Among 24 patients treated with DDP alone there were one complete and two partial responses. Twenty patients, in whom single-agent DDP failed, were treated with the combination of TAM and DDP. Of these 20 patients, 19 were evaluable for response. Among these 19 patients, there were three partial responses (16%) and three mixed responses (16%), for an overall response rate of 32% (0% was expected) (P < 0.001). If the three mixed responses are eliminated, the statistical significance is of borderline significance (P = 0.058). CONCLUSIONS: The addition of TAM to DDP can overcome established DDP resistance in a subset of patients with metastatic melanoma. PMID- 8364869 TI - Aggressive pulmonary metastasectomy for soft tissue sarcomas. AB - BACKGROUND: To evaluate the efficacy of aggressive pulmonary metastasectomy for treating soft tissue sarcomas, the clinical data on the surgical management of 23 patients with extensive pulmonary metastases from soft tissue sarcomas were reviewed. METHODS: Between January 1973 and April 1991, 9 male patients and 14 female patients were treated. Their ages ranged from 13-68 years (median, 42 years). Twenty-one patients (91%) had bilateral and multiple metastases, and two patients had solitary metastasis. The number of resected metastatic nodules ranged from 1-110 (mean, 30.5). As an initial surgical approach, median sternotomy was used on 18 patients and lateral thoracotomy on 5 patients. Eleven patients underwent two or more explorations for recurrent metastases using lateral thoracotomy. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was adopted in 10 patients since 1986. RESULTS: The actuarial 2-year and 5-year survival rates after the first pulmonary resection were 49.7% and 24.8%, respectively. Histologic type (alveolar soft part sarcoma versus synovial sarcoma, P < 0.025), histologic grade (G1 and G2 versus G3, P < 0.01), and metastatic localization (subpleural versus extrapleural, P < 0.005) were the most significant prognostic factors for aggressive pulmonary metastasectomy of soft tissue sarcomas. Application of laser surgery, absence of local recurrences, and absence of extrapulmonary metastases before pulmonary resection also correlated with better prognosis with borderline significance. CONCLUSIONS: Aggressive pulmonary metastasectomy for soft tissue sarcomas is a recommended procedure, even in the case of extensive metastases. The combination of median sternotomy and Nd:YAG laser-assisted surgery is a useful technique, especially in bilateral multiple pulmonary metastases. PMID- 8364870 TI - DNA flow cytometry and pathologic grading as prognostic guides in axillary lymph node-negative breast cancer. AB - BACKGROUND: The recurrence or mortality rate of axillary lymph node-negative invasive breast cancer has been associated with the tumor S-phase fraction, which is measured by DNA flow cytometry. Because many of the studies that established this association were performed using frozen, pulverized tumor specimens, this association could not be tested for independence from the established prognostic factors of histologic and nuclear grading. METHODS: Histologic, nuclear, and mitotic grades, DNA ploidy, and S-phase fraction (SPF) were determined from paraffin-embedded tumors obtained from 280 women with node-negative invasive ductal carcinomas using standard grading schemes and flow cytometric techniques. These variables were compared with disease-free and cancer-specific survival (CSS) in univariate and multivariate analyses of these patients. RESULTS: Tumor diameter, SPF, histologic grade, and nuclear grade were significant predictors of disease-free survival (DFS); diameter and SPF had significant associations with CSS. Cox analysis showed histologic grade to be the only independent predictor of relapse, whereas diameter and SPF were independent predictors of mortality. The patients with low nuclear or histologic grade tumors had only a 5% risk of recurrence at 5 years. In contrast, 36% of patients in this series with medium grade or high-grade high SPF tumors had a 30% risk of recurrence over the same interval. CONCLUSIONS: Histopathologic grading and flow cytometric determination of SPF appear to provide additive prognostic information for patients with early invasive ductal carcinomas of the breast. PMID- 8364871 TI - The current detectability of breast cancer in a mammographic screening program. A review of the previous mammograms of interval and screen-detected cancers. AB - BACKGROUND: The occurrence of an interval cancer in a mammographic screening program is indicative of a suboptimum effect on mortality, because the very aim of the screening is to detect as many cancers as possible and at their earliest possible stage. In several studies, the previous screening mammograms of patients with an interval cancer were reviewed and the reasons for the "missed diagnosis" were classified into four categories: "screening error" (20-29%), "minimal sign present" (30-40%), "radiographically occult" (33-58%), or "radiographically occult at diagnosis" (occult both at previous screening and diagnosis; 7-16%). A similar procedure was followed in the Nijmegen screening project with patients recently diagnosed as having interval cancer or screen-detected cancer. METHODS: The previous screening mammograms of 40 interval and 44 screen-detected cases from the breast cancer screening program in Nijmegen were reviewed and categorized as specified above. These breast cancers were diagnosed clinically before the patient was invited to the eighth screening round (interval cancer) or were detected at the eighth screening round (screen-detected cancer). All these patients had been screened in the seventh round (1987-88). RESULTS: Thirteen percent of all cases were classified as "screening error," 38% as "minimal sign present," 43% as "radiographically occult," and 6% as "radiographically occult at diagnosis." In nearly half of the screen-detected cancers, minimal signs appeared to be present on the previous screening mammogram 2 years before the diagnosis. CONCLUSIONS: Annual instead of biennial screening may advance detection in most of the "screening error" cases as well as in some in the categories "minimal sign present" and "radiographically occult" at the previous screening. Meticulous analysis of the radiologic characteristics of the "minimal sign present" cases may very well lead to results showing that earlier detection is possible without a significant decrease in the specificity of the screening test. PMID- 8364872 TI - Effect of LC9018 combined with radiation therapy on carcinoma of the uterine cervix. A phase III, multicenter, randomized, controlled study. AB - BACKGROUND: The failure rate with radiation therapy alone for Stage III cervical cancer is quite high, and therefore other modalities are being pursued as adjuvants to radiation therapy in hopes of improving the results. METHODS: A randomized, controlled, comparative study on the efficacy and safety of radiation therapy combined with LC9018 (a biologic response modifier prepared from heat killed Lactobacillus casei YIT9018) was conducted using 228 patients with Stage IIIB cervical cancer. RESULTS: LC9018 enhanced tumor regression (P < 0.1) by radiation after both 30 Gy of external radiation and at the completion of radiation therapy. The combination therapy also prolonged survival and the relapse-free interval (P < 0.05) compared to radiation alone. Analysis of survival using the Cox proportional hazard model indicated that use of LC9018 was a significant factor related to survival duration. Major side effects of combined LC9018 included fever and skin lesions at the injection site, but no severe symptoms were noted. Radiation-induced leukopenia was significantly less severe (P < 0.05) in the LC9018-combined group than in the radiation-alone group, suggesting that this agent might help to prevent leukopenia during radiation therapy. CONCLUSIONS: LC9018 was shown to be an effective agent for adjuvant immunotherapy when combined with radiation therapy. PMID- 8364873 TI - Impaired binding properties of endothelin-1 receptors in human endometrial carcinoma tissue. AB - BACKGROUND: Endothelins, potent stimulators of smooth muscle tissue activity, were recently shown to also function as mitogens for numerous cell types. The authors investigated the properties of endothelin-1 (ET-1) receptors in human endometrial tissue compared with human endometrial carcinoma tissue. METHODS: Tissue samples from 13 patients with endometrial carcinoma and from 12 women undergoing hysterectomy due to uterus myomatous were obtained immediately after surgical removal. Binding properties of the endothelin receptors were studied using 125I-labeled ET-1. RESULTS: A significant difference was demonstrated between binding properties of ET-1 receptors of these two groups. The mean maximal density (Bmax) value of the normal endometrial samples was 2029 +/- 341 fmol/mg protein, whereas that of the neoplastic samples was 356 +/- 121 fmol/mg protein. No differences were found, however, between the mean dissociation constant (Kd) values of these groups. CONCLUSIONS: These results might be compatible with the increased blood flow that characterizes malignant endometrial tissue. However, they do not indicate an important mitogenic role for ET-1 in the development of endometrial cancer. PMID- 8364874 TI - Malignant lymphoma of the uterus. Report of seven cases with immunohistochemical study. AB - BACKGROUND: Uterine lymphoma is a rare disease; therefore, information regarding histologic type, immunophenotype of tumor cells, and etiologic factors are limited. METHODS: Seven patients with uterine lymphoma, three from the corpus and four from the cervix, were collected by a nationwide study in Japan. Selection of cases was preferentially made from the "Annual of Pathologic Autopsy Cases in Japan." RESULTS: All cases with cervical lymphoma presented with vaginal bleeding. Abdominal pain or backache was observed in patients with corpus lymphoma. The age ranges of patients with corpus and cervical lymphomas were 46 78 years of age (mean, 63 years) and 30-71 years of age (mean, 53 years), respectively. Information about clinical staging was available for six patients; two patients with Stage I, three patients with Stage II, and one patient with Stage III. A definite diagnosis of uterine lymphoma was made by biopsy in all cases. Total hysterectomy, with or without bilateral salpingo-oophorectomy, was carried out in three patients, and tumor resection was carried out in one patient. Adjuvant therapy was given in six cases. Follow-up showed that five patients died due to tumor within 1 year of treatment. Histologically, all cases were non-Hodgkin lymphoma showing a diffuse pattern of proliferation. All but one were diffuse large cell type. Immunohistochemistry revealed the tumor cells in all cases were of B-cell nature. Expression of HLA-DR antigen was evaluable in four cases, of these three showed an increased expression on the vascular endothelium. CONCLUSIONS: Uterine lymphoma comprises exclusively B-cell type. PMID- 8364875 TI - A phase II study of continuous infusion 5-fluorouracil in advanced hormone refractory prostate cancer. An Illinois Cancer Center Study. AB - BACKGROUND: 5-Fluorouracil (5-FU) has been previously associated with therapeutic benefit in hormone refractory prostate cancer. However, no previous study has administered 5-FU as a prolonged continuous infusion, which may be the optimal schedule for this cell-cycle specific agent. METHODS: Therefore, 25 patients were treated with 5-FU administered as a continuous intravenous infusion at a dose of 1000 mg/m2/day for 5 days every 28 days. Eligibility required disease defined by bidimensionally measurable lesions or evaluable lesions on bone scan or radiograph with elevated serum levels of prostate-specific antigen (PSA), no severe cytopenias, and an Eastern Cooperative Oncology Group performance status less than 3. Prior chemotherapy was not allowed. Dose modifications were specified for mucositis and hematologic toxicity. RESULTS: Eighteen of 22 patients were evaluable for response and toxicity, whereas 4 were evaluable for toxicity alone. Toxicity was significant using this dose and schedule and included episodes of sudden death (one patient), paroxysmal supraventricular tachycardia (one patient), and congestive heart failure (one patient). Other Grade 3 toxicities included stomatitis (two patients) and diarrhea (one patient). Significant myelosuppression did not occur. Objective responses were not observed, but 12 patients experienced stable disease with a median duration of 4 months. CONCLUSIONS: Infusional 5-FU can not be recommended for the treatment of advanced hormone refractory prostate cancer. PMID- 8364876 TI - Malignant lymphoma of bladder. Report of three cases and review of the literature. AB - BACKGROUND: The significance of long-standing cystitis has been postulated as a causal factor in malignant lymphoma of bladder. METHODS: The authors reviewed 3 cases of primary malignant lymphoma of the urinary bladder and an additional 27 cases described in the literature (25 from Western countries and 2 from Japan). Clinical and pathologic findings in the total 30 cases are summarized. RESULTS: The majority of patients presented with gross hematuria and were between 20 and 85 years of age (median age, 64 years). Marked female preponderance was found (male to female ratio, 1:6.5). Six patients (20%), all of whom were women, out of 30 had a history of chronic cystitis. Macroscopic findings showed a solitary mass (22 cases), multiple masses (6 cases), or a diffuse lesion without nodule formation (2 cases). The vast majority of bladder lymphoma were non-Hodgkin lymphoma (NHL) of B-cell type; among them, 14% were follicular lymphomas. Follow up indicated that NHL of bladder had a favorable prognosis. CONCLUSIONS: Malignant lymphoma of bladder is characterized by a preponderance in women, who are occasionally affected by chronic cystitis. PMID- 8364877 TI - Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for infiltrating transitional cell carcinoma of the bladder. AB - BACKGROUND: Based on the excellent results with combination chemotherapy such as M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in patients with advanced disease, neoadjuvant chemotherapy has been advocated to improve survival and in some cases to permit bladder conservation. METHODS: A Phase II study of neoadjuvant M-VAC chemotherapy was performed in patients with T2-T4N0M0 bladder tumors. After clinical staging, three cycles of M-VAC were given. After patients underwent postchemotherapy clinical restaging, pathologic restaging (partial or radical cystectomy) was planned. RESULTS: Forty-six patients are evaluable. A clinical response was attained in 78%. Six patients (13%) had stable disease, and four (9%) had progression. After chemotherapy, 17 patients underwent radical cystectomy, none of whom were pTO. In this group, 10 of the 17 (59%) are alive at a median follow-up of 37+ months (range, 8-62+ months). Eleven patients had a partial cystectomy; 7 of the 11 (64%) are alive, 6 (55%) with a preserved bladder. Eighteen patients had clinical restaging only, and did not have pathologic staging. Median follow-up for this group is 36+ months (11-65+ months). Twenty-one of the 29 (72%) patients managed with conservative surgery or transurethral resection of the bladder alone are alive with a functional bladder. Median survival for all patients has not yet been reached. Two-year survival is 82%, and 3-year survival is 70%. CONCLUSIONS: The current study is of interest in terms of bladder conservation. Assessment of the true success of any bladder preserving treatment will require longer follow-up. PMID- 8364879 TI - Estrogen receptors and cathepsin D in human thyroid tissue. AB - BACKGROUND: To investigate the significance of estrogen receptors (ER) in the pathogenesis of thyroid dysplasia, the authors analyzed, by analogy with breast cancers, ER and three estrogen-regulated proteins: progesterone receptor (PR), cathepsin D, and pS2 protein, in cytosols of 42 human thyroid tissues. METHODS: ER and PR were measured by an immunoenzymatic assay and cathepsin D and pS2 by an immunoradiometric assay. Tissue specimens included 7 normal tissues, 6 benign nodules, 8 toxic adenomas, 7 from patients with Graves disease, and 14 carcinomas. RESULTS: ER was present at very low concentrations, with no statistical difference between neoplastic and nonneoplastic tissues. The mean levels of cathepsin D, expressed as pmol/mg protein minus thyroglobulin, were higher in the 14 carcinomas (P = 0.0003), the 7 specimens from patients with Graves disease (P = 0.006), and the 8 toxic adenomas (P = 0.04) than in the 7 normal thyroid tissues. A significant difference also was observed between the carcinomas (P = 0.003) and six benign nodules. Compared to TNM parameters, cathepsin D concentrations correlated with tumor size: higher cathepsin D levels were found in pT4 than in pT2 and pT3 carcinomas. All the tissues tested were negative for PR and pS2 protein. CONCLUSIONS: The results clearly indicate a significant difference between neoplastic and normal thyroid tissue in terms of the amount of cathepsin D, but not that of ER. This suggests that cathepsin D probably is not regulated by estrogen but simply is a marker of protease activity during invasion by thyroid carcinomas. PMID- 8364878 TI - Increased uptake of iodine-131 in metastases of differentiated thyroid carcinoma associated with less severe hypothyroidism following total thyroidectomy. AB - BACKGROUND: In an attempt to determine possible factors affecting the efficacy of iodine-131 (I-131) treatment for metastatic thyroid carcinoma, the authors focused their efforts on thyroid functions after total thyroidectomy. METHODS: Between 1980 and 1991, 47 patients with lung metastases of differentiated thyroid carcinoma were treated with I-131. Relationships of the images on post-therapy scans with various clinical features were studied. RESULTS: Among them, 28 (59.6%) showed I-131 uptake in the metastases on post-therapy scans. Younger patients had lesions that concentrated more radioactive iodine than did those of older patients. The amount of I-131 concentrated in the metastatic lesions correlated with serum triiodothyronine (T3), thyroxine (T4), and thyroglobulin levels and inversely with serum thyroid-stimulating hormone (TSH) levels determined at the time of therapy. Serum T3 and T4 levels were significantly higher in 28 patients with positive scans than in 19 patients with negative scans. Most patients who had metastases with markedly increased radioactivity were euthyroid or mildly hypothyroid, suggesting that thyroid hormones produced by tumor masses compensated for severe hypothyroidism after total thyroidectomy, and showed favorable responses to the treatment. In three patients successfully treated, decreases in serum thyroglobulin levels and the size of metastatic lesions were accompanied by the development of severe hypothyroidism. CONCLUSIONS: The presence of a large amount of metastatic functioning thyroid tissues responsive to I-131 treatment can be suspected in patients with less severe hypothyroidism after total thyroidectomy. PMID- 8364880 TI - Virilizing adrenocortical tumors in adult women. Report of 10 patients, 2 of whom each had a tumor secreting only testosterone. AB - BACKGROUND: Virilizing adrenocortical tumors are uncommon in adult women. These lesions generally secrete dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), but not testosterone, which usually is produced by ovarian tumors. Exceptionally, adrenal growths may give off testosterone and no other assessable androgen. The detection of the site of excess testosterone yield is paramount for proper surgery. The true nature of the growth often is unpredictable, even at the time the pathologist examines the surgical specimen. METHODS: The workup in a virilized adult woman relies on biochemical tests such as 24-hour urinary 17-KS and 17-OHCS levels and plasma corticosteroid levels (testosterone, DHEA, DHEAS, and androstenedione), and on modern imaging studies such as ultrasonography, computed tomography, and digital angiography. RESULTS: Among a series of 190 adrenal tumors collected in the last 30-year period, only 10 virilizing growths (5.3%) were detected. Two cases of virilization mixed with cushingoid features were observed. In two other cases, reported in detail, the tumor secreted testosterone only, without other assessable androgens. Seven of the 10 tumors were malignant. CONCLUSIONS: In cases of tumors secreting testosterone only, high-resolution imaging has contributed significantly in pinpointing the site of the growth, whereas dynamic hormone testing, using selective stimulation or suppression studies, has been misleading. The malignant nature of the growth may be revealed only by the presence of metastases, because pleomorphism and capsular and vascular invasion have been detected histologically in clinically benign tumors. The prognosis for large tumors usually is dismal. PMID- 8364881 TI - Elevated serum CA 125 secondary to tuberculous peritonitis. AB - A 33-year-old African-American woman presented with a 10-day history of abdominal pain, fever to 104 degrees F, and ascites. Her PPD converted to positive. A serum CA 125 level was 708 U/ml before therapy. Tuberculous peritonitis was diagnosed via peritoneal biopsy. The CA 125 level was used to follow response to treatment and was undetectable after 12 weeks of antituberculous treatment. This tumor marker may be used to follow disease activity in non-neoplastic ascitic states. PMID- 8364882 TI - Infantile choriocarcinoma. Re-examination of a potentially curable entity. AB - Choriocarcinoma presenting in an infant or neonate is a rare entity that in the past has been uniformly fatal. The authors present the first reported case of choriocarcinoma successfully treated in a 3-week-old infant. Choriocarcinoma was not suspected in this case until pathologic examination revealed the diagnosis. In retrospect, however, the case fits well into the classic "infantile choriocarcinoma syndrome" initially described by Witzleben in 1968. Review of additional cases reported since the initial description validates Witzleben's initial observations and also indicates that the original definition should be broadened to include other significant presentations of the disease not initially appreciated, specifically anemic infants with central nervous system symptoms as well as newborns and older children. The importance of making a correct and rapid diagnosis is emphasized by the successful outcome in this case where aggressive surgery and subsequent chemotherapy have been curative. Serum beta-human chorionic gonadotropin (beta-HCG) levels have been uniformly positive, providing easy confirmation of the diagnosis. Because the mother can also be affected, an appropriate diagnosis of the infant may also lead to more rapid diagnosis and treatment of the mother. PMID- 8364883 TI - Inflammatory myofibroblastic tumor in children. AB - The authors presented the cases of two children with inflammatory myofibroblastic (IMF) tumor and reviewed the literature to facilitate the preoperative recognition, delineate the clinical features, and describe the natural history of this entity. The first child had IMF tumor arising from the mesentery of the small intestine. He presented with an abdominal mass associated with severe inflammatory response manifested by fever, impaired growth, thrombocytosis, and microcytic, hypochromic anemia. After surgical resection, his fever resolved and his growth rate and the laboratory abnormalities normalized. Five months after initial diagnosis, the fever, anemia, and thrombocytosis recurred along with two tumors arising from the omentum and the abdominal soft tissue. After the second surgery, he remains free of recurrent disease for 30 months. The second child presented with a lung mass that was radiologically indistinguishable from pulmonary sequestration. After surgical resection, she remains free of recurrent disease for 18 months. IMF tumor should be considered in any solid tumor that occurs in association with a chronic inflammatory response. IMF tumor should also be considered in the differential diagnosis of pulmonary sequestration. PMID- 8364884 TI - Elective inguinal lymph node irradiation for pelvic carcinomas. The University of Florida experience. AB - BACKGROUND: There is little published information pertaining to elective inguinal lymph node irradiation for carcinomas originating in the pelvis that place the inguinal lymph nodes at risk. METHODS: Between October 1964 and October 1988, 164 patients with primary carcinomas originating in the pelvis that placed the inguinal lymph nodes at risk for subclinical disease received elective inguinal lymph node irradiation at the University of Florida. All patients had a minimum follow-up of 2 years from the start of radiation therapy. Primary sites included the penis, urethra, vulva, anal canal, distal rectum (within 4 cm of the verge), and the cervix or vagina when the tumor involved the distal one-third of the vagina. In 148 patients, both groins were clinically negative; in 16 patients, one groin was positive and the other negative by clinical examination. Treatment techniques were individualized according to the primary site. Tumor doses to the inguinal lymph nodes varied, although more than 70% of patients received 4500 5000 cGy (range, 2650-6780 cGy) over 5 weeks (range, 2-7 weeks) at 180-200 cGy per fraction. Patients were excluded from the analysis of disease control in the inguinal area if they died less than 2 years from treatment with the inguinal lymph nodes continuously disease free or if they experienced recurrence at the primary site with the inguinal lymph nodes clinically negative at the time of recurrence. RESULTS: The inguinal lymph node control rate was 96% (101 of 105). No patient in whom recurrent disease developed in the inguinal lymph nodes underwent salvage therapy. CONCLUSIONS: Elective irradiation of the inguinal lymph nodes is highly effective in controlling subclinical disease from carcinomas originating in the pelvis and can be accomplished with minimal acute or long-term complications. PMID- 8364885 TI - Assessment of the mutagenic activity of some acenaphtho(1,2-b)quinolines. AB - The mutagenic activity of four substituted acenaphtho(1,2-b)quinolines were evaluated using the Ames test (Salmonella assay). The compounds tested were acenaphtho(1,2-b)quinoline (1) and its 10-methoxy (2), 10-methyl (3) and 10-nitro (4) derivatives. Compounds 1 and 3 were found to be non-mutagenic, but compound 2 was found to be mutagenic with metabolic activation only. However, compound 4 was found to be very active with or without activation. PMID- 8364886 TI - Carcinoembryonic antigen mediates in vitro cell aggregation induced by interferon gamma in a human colon cancer cell line: requirement for active metabolism and intact cytoskeleton. AB - The homotypic cell aggregation of a carcinoembryonic antigen (CEA) positive colon cancer cell line (Colo 205) was induced in vitro by interferon-gamma (IFN-gamma) treatment. Divalent cations were required for this aggregation, as it was inhibited by EDTA. The partial inhibition by cytochalasin B and the complete inhibition by a mixture of sodium azide and 2-deoxyglucose suggests that the aggregation requires the integrity of cytoskeleton and active metabolism. The expression of CEA was increased in the cytoplasm and on the membrane of Colo 205 by IFN-gamma treatment. Furthermore, this aggregation was inhibited completely by anti-CEA monoclonal antibody (mAb) and partially by mAb against intercellular adhesion molecule-1. This in vitro study suggests that CEA molecule participates in the IFN-gamma induced homotypic adhesion of some CEA positive cancer cells and that IFN-gamma has an important role in the regulation of cell-cell interaction mediated by CEA molecule. PMID- 8364887 TI - Transforming growth factor beta 1-induced delay of cell cycle progression and its association with growth-related gene expression in mouse fibroblasts. AB - TGF beta-induced cell cycle progression is relatively slower than that induced by EGF or PDGF-BB. Further, TGF beta delays EGF or PDGF-induced 5-phase entry in C3H 10T1/2 mouse fibroblasts. In accordance with this delay, the induction of mRNA level of 'immediate early genes' such as c-myc, c-fos, c-jun and junB by TGF beta has slower kinetics compared with those of EGF. TGF beta induces c-sis gene, suggesting possible involvement of secondary growth stimulation by PDGF-like proteins. However, anti-PDGF-AB antibody, which was inhibitory to FDGF-BB-induced [3H]thymidine incorporation, did not block TGF beta-induced DNA synthesis. These results first demonstrate that the delay of cell cycle progression by TGF beta is closely associated with the altered regulation of growth-related gene expression in fibroblasts. PMID- 8364888 TI - Interleukin-6 and tumour necrosis factor alpha synergistically block S-phase cell cycle and upregulate intercellular adhesion molecule-1 expression on MCF7 breast carcinoma cells. AB - The effect of IL-6 and TNF alpha were studied on human MCF7 breast cancer cells. Synergistic interaction between IL-6 and TNF alpha, on the growth inhibition (50% reduction in the percentage of S-phase cells) and the upregulation of ICAM-1 expression (4 to 11-fold increase) was shown using flow cytometric methods. IL-6 and TNF alpha alone had negligible effect on the cell cycle. The individual effect of IL-6 resulted in down-regulation of ICAM-1 expression (30-35%), while TNF alpha always upregulated ICAM-1 (1.5 to 4-fold increase). The combined effect of IL-6 and TNF alpha consistently caused an increased expression of ICAM-1, which was greater than the sum of each one alone and also sustained for 72 h following cytokine withdrawal. PMID- 8364889 TI - Increased risk of lung cancer in Japanese smokers with class mu glutathione S transferase gene deficiency. AB - Japanese lung cancer patients (n = 121) and community controls (n = 201), both with current smoking history and aged < or = 69, were compared for the rates of class mu glutathione S-transferase (GSTmu) negative genotype detected by polymerase chain reaction. The prevalence of the GSTmu negative genotype was 45.3% in the community control group and 68.4%, 69.2%, 54.3% and 72.7% in the squamous cell carcinoma, small cell carcinoma, adenocarcinoma and other primary lung cancer groups, respectively. Odds ratios adjusted for age, sex composition and smoking index by multiple logistic regression analysis were 2.71 (1.23-5.99), 2.72 (1.11-6.66), 1.33 (0.68-2.60), and 3.27 (0.83-12.81), respectively. These results suggest that smokers with a GSTmu negative genotype are at higher risk for bronchial carcinoma than smokers with positive genotype. PMID- 8364890 TI - Tri-n-butyltin chloride promotes morphological transformation and induces proliferin expression in C3H10T1/2 cells. AB - Transcripts from the murine gene family proliferin, which are increased by a wide assortment of chemical promoters of C3H10T1/2 cell morphological transformation, were shown to be induced by tri-n-butyltin chloride at concentrations above 50 nM. Two-stage transformation assays, with 3-methylcholanthrene as inducer and tri n-butyltin chloride as promoter, were performed to determine if promotion of morphological transformation and proliferin induction were properties shared by this compound. Tri-n-butyltin chloride synergistically enhanced focus formation at concentrations ranging from 20 to 75 nM. Di-n-butyltin dichloride, n-butyltin trichloride and tin (II) chloride, but not tin (IV) chloride, were also effective inducers of proliferin. Changes in patterns of TPA-inducible, secreted proteins, including those likely to be proliferin, were detected following organotin treatment of confluent monolayers. Tri-n-butyltin chloride resembles other agents active as promoters in C3H10T1/2 two-stage transformation assays by possessing an ability to induce proliferin expression. PMID- 8364891 TI - Retinoic acid induces insulin-like growth factor II expression in a neuroblastoma cell line. AB - Insulin-like growth factor II (IGF-II) is implicated in the development of the vertebrate neural circuitry, and increases neurite growth in vitro and in vivo. We examined the relationship of IGF-II expression to the in vitro differentiation induced by retinoic acid (RA). We find that RA stimulates an increase in IGF-II messenger RNA (mRNA) in the SK-N-SH (SH) neuroblastoma cell line. An increase of IGF-II mRNA is detected within 12 h of treatment and precedes morphological differentiation. A RA dose response test indicates that an increase in IGF-II mRNA occurs within 2 days in SH cells treated with doses of RA from 1 x 10(-8) to 1 x 10(-5) M. We suggest that IGF-II expression may be regulated either directly or indirectly by RA in vitro and may lead to neuroblastoma differentiation. PMID- 8364892 TI - Diamine oxidase activity in rat brain carcinogenesis and in gliomas. AB - In the early stages of brain carcinogenesis induced by transplacental administration of N-ethyl-N-nitrosourea to BD IX rats, a constant increase in the activity of cerebral diamine oxidase, the rate-limiting enzyme in terminal catabolism of polyamines, was observed. Gliomas, which developed between the fifth and eight month of extrauterine life, showed an 8-fold increase in enzyme activity compared with normal brain from rats of the same age. Concomitantly, an 11-fold enhancement in putrescine, a physiological substrate of diamine oxidase, was also found. Such findings indicate that an increase in oxidative putrescine catabolism via diamine oxidase takes place in transformed cells and in gliomas and is probably linked to an activation of polyamine synthesis and turnover. PMID- 8364893 TI - Argyrophilic nucleolar organizer regions (AgNORs) in inflammatory pre-malignant and malignant lesions of the uterine cervix. AB - Nuclear organizer regions (NORs) code for ribosomal RNA and are associated with non-histone nucleoproteins, which can be identified by silver staining (AgNORs). AgNORs have been correlated to proliferative activity of tumors and hence may be prognosis-related. The present study evaluates AgNOR counts in inflammatory lesions of the uterine cervix, cervical intra-epithelial neoplasia, and invasive cervical squamous carcinoma. Significant variation in AgNOR counts were observed between the three study groups, with invasive carcinoma showing maximum counts. Further, a highly significant positive correlation was observed between AgNOR counts and tumor progression. These results therefore suggest that AgNOR counts may be of significance in the evaluation of cervical carcinogenesis and could elaborate histopathological diagnosis of cervical lesions. PMID- 8364894 TI - A study of tobacco carcinogenesis. LI. Relative potencies of tobacco-specific N nitrosamines as inducers of lung tumours in A/J mice. AB - Tobacco-specific N-nitrosamines (TSNA) are formed from nicotine and the minor Nicotiana tabacum alkaloids during tobacco processing and tobacco smoking. The TSNA are the most abundant strong carcinogens in smokeless tobacco and in smoke. In this comparative study six TSNA and two major volatile N-nitrosamines of cigarette smoke are assayed for their relative tumorigenicities in strain A/J female mice and for their potential to induce lung tumors. N-nitrosodimethylamine was the most potent inducer of lung adenoma in the A/J mouse model followed in order of decreasing potencies by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N-nitrosopyrrolidine, N' nitrosonornicotine and N'-nitrosoanabasine. 4-(Methylnitrosamino)-1-(3-pyridyl)-1 butanol and 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid were inactive. The relative tumorigenic activities of the tobacco-specific nitrosamines in strain A/J mice compare well with the available data for their relative tumorigenic activities in F344 rats and Syrian golden hamsters. PMID- 8364895 TI - Formation and growth of multicellular spheroids in media containing low concentrations of agarose. AB - Human melanoma HMV-1 cells formed efficiently multicellular spheroids in media containing low concentrations (0.001-0.01%) of agarose (LCAM). In addition, the spheroids were prevented from deformation without apparent delay of the growth rate. On the other hand, spheroid formation was inhibited markedly by LCAM in the case of murine melanoma B16 cells. Also, LCAM could not prevent the B16 spheroids from deformation. These results indicate that LCAM acts differently depending on the cell types used for spheroid formation. PMID- 8364896 TI - The effects of phenethyl isothiocyanate on benzo[a]pyrene-induced tumors and DNA adducts in A/J mouse lung. AB - The effects of phenethyl isothiocyanate (PEITC) on benzo[a]pyrene (B[a]P)-induced DNA adducts and pulmonary adenomas in A/J mice were investigated. Groups of 24 male and 24 female A/J mice were administered PEITC by gavage at doses of 0.075, 0.25, 0.50, and 0.75 mmol/kg (12, 41, 82, 122 mg/kg) for 6 consecutive days. A single dose of 0.40 mmol/kg (100 mg/kg) B[a]P was given by i.p. injection after the fourth dose of PEITC. A positive control received only a single i.p. injection of B[a]P, 100 mg/kg body weight. The vehicle control group was administered corn oil by gavage for 6 consecutive days and a single i.p. injection of tricaprylin following 4 doses of corn oil. In addition, 2 groups of 24 male and 24 female mice each were administered PEITC at dose levels of 12 and 122 mg/kg body weight to evaluate the effects of this compound alone. Body weight loss occurred in both males and females in the 0.25, 0.50, and 0.75 mmol/kg PEITC groups relative to B[a]P controls and to untreated controls during the first week of the study. Tumor incidence and multiplicity in the PEITC-treated groups, evaluated 7 months after B[a]P administration, were not significantly different when compared with the B[a]P group. The results of a subsequent DNA adduct bioassay, using similar dose levels of PEITC and B[a]P, correlated with the results of the tumorigenesis study, indicating that pretreatment with PEITC did not inhibit the formation of B[a]P-DNA adducts in the lungs of A/J mice. PMID- 8364897 TI - Antiproliferative action of the steroid RU486 in cultured human lymphoma cells. AB - The antiproliferative properties of the synthetic steroid RU486 on the human lymphoma cell line Daudi are described. In suspension cultures, RU486 (10 microM) caused a time dose and cell density dependent reduction of cell proliferation. This effect was reversed within 48 h of withdrawal of RU486 from the growth medium. High concentrations of foetal calf serum can mask the inhibitory effect. In semi-solid cultures RU486 also impaired cell proliferation. Thus RU486 was able to suppress in this tumor cell line the expression of some properties frequently associated with the transformed status of the cells. PMID- 8364898 TI - Release of intracellular calcium by prenylamine in human ovarian tumour cells. AB - The effects of the calcium antagonist prenylamine on intracellular calcium concentration were studied in a human ovarian carcinoma cell line, OVCAR-3. Exposure of cells to 100 microM prenylamine resulted in nearly a 10-fold increase in cytosolic free calcium concentration ([Ca2+]i) as measured by Fura-2 fluorescence. In calcium-free medium, although the increase in [Ca2+]i caused by prenylamine was smaller, it was still substantial compared with the basal level. Efflux experiments with 45Ca showed that 100 microM prenylamine increased calcium efflux by 70% compared with control, indicating active extrusion of the elevated [Ca2+]i. The sluggish nature of calcium release and its independence from the pool activated by ionomycin suggest that the calcium was probably not released from endoplasmic reticulum. These results, although paradoxical, provide a new insight into the possible mechanism of action of prenylamine in causing cancer cell death. PMID- 8364899 TI - Formation of DNA adducts and oxidative DNA damage in rats treated with 1,6 dinitropyrene. AB - In vitro metabolism studies have indicated that the tumorigenic environmental pollutant 1,6-dinitropyrene has the potential to bind covalently to DNA and to induce oxidative DNA damage. We have determined if 1,6-dinitropyrene treatment will cause both types of DNA damage in vivo. Female Sprague-Dawley rats were given a single intraperitoneal injection of 1,6-dinitropyrene, and covalent DNA adduct formation, as indicated by the presence of N-(deoxyguanosin-8-yl)-1-amino 6-nitropyrene, and oxidative DNA damage, as indicated by increases in 5 hydroxymethyl-2'-deoxyuridine and 8-hydroxy-2'-deoxyguanosine, were assessed at 3, 12, 24 and 48 h after dosing. 32P-postlabeling analyses of DNA isolated from liver, mammary gland, bladder and nucleated blood cells indicated the formation of N-(deoxy-guanosin-8-yl)-1-amino-6-nitropyrene, with the levels being highest in the bladder. 5-hydroxymethyl-2'-deoxyuridine was detected in DNA from each of these tissues, and the levels of this oxidized nucleoside were higher in the mammary glands and livers of 1,6-dinitropyrene-treated rats. 1,6-Dinitropyrene dosing did not affect the levels of 8-hydroxy-2'-deoxyguanosine in these two tissues. These results indicate that exposure to 1,6-dinitropyrene can result in increased levels of 5-hydroxymethyl-2'-deoxyuridine in addition to covalent DNA adduct formation. PMID- 8364900 TI - Antipromoting effects of 5-lipoxygenase inhibitors, 3-nitro-2,4,6- trihydroxybenzamide derivatives, on TPA-promoted transformation in BALB 3T3 cells. AB - In order to discover the role in the promotion process of 5-lipoxygenase (5-LO), a key enzyme in the arachidonate cascade, the antipromoting effects of the 5-LO inhibiting 3-nitro-2,4,6-trihydroxybenzamide (NTB) derivatives were studied in a two-stage transformation assay system using BALB 3T3 cells. All compounds inhibited TPA-promoted transformation in a dose-dependent manner. Most of them achieved a 70-80% inhibition. Good correlations were observed between the inhibition of TPA-promoted transformation and that of 5-LO. These results indicate that 5-LO plays an important role in the promotion stage of the transformation of BALB 3T3 cells. PMID- 8364901 TI - Tumor promotion in a breast cancer model by exposure to a weak alternating magnetic field. AB - In view of the methodological problems of epidemiological studies on associations between exposures to 50/60 Hz magnetic fields (MF) and increased incidence of cancers, laboratory studies are necessary to determine if 50/60 Hz MF are cancer promoters or can progress cancers. The objective of the present study was to determine if an alternating MF of low flux density exerts tumor-promoting or co promoting effects in a model of breast cancer in female rats. Mammary tumors were induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). A group of 99 rats was exposed to a homogeneous MF of 50 Hz, 100 microT (microtesla), for 24 h/day 7 day/week for a period of 91 days; another group of 99 rats was sham exposed under the same environmental conditions as the MF-exposed rats. The exposure chambers were identical for MF-exposed and sham-exposed animals. DMBA was administered orally at a dose of 5 mg/kg at the first day of exposure and at weekly intervals thereafter up to a total dose of 20 mg per rat. The animals were palpated once weekly to assess the development of mammary tumors. In controls, DMBA induced tumors in about 40% of the animals within three months of first application. Eight weeks after DMBA application the MF-exposed rats exhibited significantly more tumors than sham-exposed animals. This difference in the rate of tumor development was observed throughout the period of exposure. At the end of the three-month period of MF exposure the tumor incidence in MF-exposed rats was 50% higher than in sham-exposed rats, the difference being statistically significant. Furthermore, the size of tumors as estimated by palpation was significantly larger in the MF-exposed compared to sham-exposed rats. The data demonstrates that long-term exposure of DMBA-treated female rats to an alternating MF of low flux density promotes the growth and increases the incidence of mammary tumors, thus strongly indicating that MF exposure exerts tumor-promoting and/or copromoting effects. PMID- 8364902 TI - Induction of hepatic nodules in the rat by aristolochic acid. AB - Aristolochic acid (AA), used as an anti-inflammatory agent in the past, is known to be mutagenic and carcinogenic to several organs of the rat, including forestomach, renal pelvis and urinary bladder. However, despite the induction of DNA adducts in the liver, no carcinogenic potential of AA has been reported in the latter organ. The present study was based on the rationale that the lack of carcinogenicity of AA to the liver could be because this chemical may not be necrogenic at the doses examined and liver cell proliferation has been established as an essential component for initiation of liver carcinogenesis in the rat. The results indicated that AA is non-necrogenic to the rat liver. However, a single non-necrogenic dose of AA (10 mg/kg b.w., i.p.) given 18 hours after 2/3 partial hepatectomy initiated liver cell carcinogenesis. The initiated cells are promotable with 1% dietary orotic acid, a liver tumor promoter, to form glutathione-S-transferase 7-7 positive hepatic foci and nodules. PMID- 8364903 TI - Alterations in populations of GST-p-immunoreactive single hepatocytes and hepatocellular foci after a single injection of N-nitrosodiethylamine with or without phenobarbital promotion in male F344/NCr rats. AB - The fate of placental glutathione S-transferase (GST-P)-immunoreactive hepatocytes, detectable in livers of rats soon after treatment with N nitrosodiethylamine (DEN), was examined sequentially with or without phenobarbital (PB) promotion. Group 1 male F344/NCr rats were administered a single i.p. injection of 200 mg DEN per kg body weight at 5 weeks of age. Group 2 rats were given 500 ppm PB in the diet two weeks after the DEN treatment. Groups of six rats were sequentially sacrificed 16, 42, 70, 126 and 238 days after DEN injection. In DEN-treated rats, GST-P immunoreactive hepatocytes (single cells and multiple cell foci) were detectable 16 days after DEN, the total numbers decreasing by day 70 and thereafter rising again. In the early stages the proportion of single immunoreactive hepatocytes was prominent, but with time a gradual increase in small GST-P+ hepatocellular foci and larger foci became evident. Feeding of PB to rats for 16-238 days after a single DEN injection resulted in increases of both single cells and foci, especially foci composed of more than three hepatocytes. The growth response was increasingly pronounced with time. Adenomas or carcinomas were only observed at 126 or 238 days. Numbers of GST-P+ foci far exceeded the numbers of foci visible in hematoxylin-eosin (H & E) stained sections, and a few H & E foci were negative for GST-P. Many GST-P+ foci smaller than ten cells were composed of histologically normal hepatocytes. Almost all GST-P+ foci identifiable in H&E stained sections were larger than ten cells, consisted of clear cells (in both groups) or mixed (clear-eosinophilic) cells in PB-exposed rats, and appeared to be evenly distributed throughout the three zones of the liver. These results suggest that the promotive effect of PB is most evident as an increase in larger hepatocyte populations composed of more than three GST-P+ hepatocytes, rather than in increasing the populations of single GST P immunoreactive cells. PB may cause clonal expansion of these single GST-P reactive hepatocytes. This study provides evidence for the hypothesis that some of the GST-P reactive hepatocytes are initiated cells. PMID- 8364904 TI - A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line. AB - A cyclic octapeptide (patellamide D) isolated from the marine tunicate, Lissaclinum patella, acts as a resistance-modifying agent in the multidrug resistant CEM/VLB100 human leukemic cell line. A three-day microculture tetrazolium proliferation assay was used to determine the 50% inhibitory concentration (IC50) for vinblastine, colchicine and adriamycin and calculate the degree of resistance modulation. Patellamide D at 3.3 microM was compared with 5.1 microM verapamil in modulating drug resistance in vitro. The IC50 for vinblastine was reduced from 100 ng/ml to 1.5 ng/ml in the presence of patellamide D or to 2.1 ng/ml when exposed to verapamil. Colchicine cytotoxicity was enhanced only 1.4-fold by verapamil, as compared with 2.8-fold using patellamide D (IC50 was reduced from 140 ng/ml to 100 ng/ml or 50 ng/ml). Adriamycin toxicity was reduced from IC50 > 1000 ng/ml to 110 ng/ml and 160 ng/ml when coexposed to patellamide D and verapamil, respectively. Our results indicate that patellamide D acts as a selective antagonist in multidrug resistance and stresses the importance of investigating marine-derived compounds as a potential new source for modulators of the drug-resistance phenotype. PMID- 8364905 TI - Interleukin 10 transfected into Chinese hamster ovary cells prevents tumor growth and macrophage infiltration. AB - Expression of cytokines in tumor cells provides a sensitive modality to analyze the consequences of local cytokines in vivo on tumor infiltrating cells and tumorigenicity. We have transfected Chinese hamster ovary (CHO) cells with an interleukin 10 (IL-10) expression vector. CHO-IL10 cells although unaltered with respect to their in vitro growth lost tumorigenicity, both in nude and in SCID mice and in an IL-10 dose dependent manner. In addition, CHO-IL10 cells suppressed the growth of equal numbers of coinjected but not of contralaterally injected CHO cells. Immunohistology with anti-CR3/Mac-1 and anti-Mac-3 monoclonal antibodies revealed that CHO tumors were substantially infiltrated by macrophages. However, in CHO-IL10 tumors macrophages were virtually absent within the tumor tissue. Our results suggest that IL-10 indirectly suppresses tumor growth of certain tumors by inhibiting infiltration of macrophages which may provide tumor growth promoting activity. PMID- 8364906 TI - Histologically benign or low-grade malignant tumors adjacent to high-grade ovarian carcinomas contain molecular characteristics of high-grade carcinomas. AB - It is presently not clear if ovarian carcinomas arise de novo or from benign precursors (cystadenomas) and if high-grade malignant tumors (carcinomas) develop from preexisting low-grade carcinomas. The presence of allelic losses on chromosome 11p15.5 distinguishes high-grade ovarian carcinomas from either low grade carcinomas or cystadenomas. We therefore examined the distribution of such losses in different parts of heterogeneous tumors showing mixed histological grades or showing adjacent large histologically benign neoplasms. The results showed that all neoplastic areas, including those that were histologically benign or compatible with low-grade carcinomas, contained allelic losses at the above locus. This suggests that the morphologically less aggressive portions of these heterogeneous tumors were not typical cystadenomas or low-grade carcinomas and contained molecular abnormalities indicative of at least a predisposition to the high-grade carcinoma phenotype. PMID- 8364907 TI - Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene. AB - Centrocytic lymphoma (CC) and intermediately differentiated lymphocytic lymphoma (IDL) are B-cell non-Hodgkin's lymphomas composed of lymphocytes presumably derived from follicle mantle cells. In these lymphomas, a specific chromosomal translocation, t(11;14)(q13;q32), has been described. Previous studies suggested an association between t(11;14) chromosomal translocations and BCL-1 rearrangements. To evaluate the association between BCL-1 rearrangements and CC/IDL, Southern blot analysis was performed on a panel of 20 cases of CC/IDL, 22 cases of morphologically similar non-Hodgkin's lymphomas, 11 cases of chronic B cell leukemias, and 2 cases of myelomas. We used various probes covering a considerable proportion of the 120-kilobase BCL-1 locus, and rearrangements in 50% of CC/IDL (10 of 20) were detected. In CC, all 4 breakpoints were located at the major translocation cluster (MTC). In contrast, in IDL, rearrangements were detected in 3 different cluster regions: 2 cases in the MTC, 2 cases with a breakpoint 24 kilobases outside the MTC, and 2 additional cases with breakpoints found 3 kilobases 5' of the first exon of the PRAD1/CCND1 gene, which is located 120 kilobases outside the MTC. In addition, one leukemia showed a breakpoint 63 kilobases outside the MTC. In all cases, there was comigration of the rearranged 11q13 fragment and the immunoglobulin heavy chain-joining gene complex, indicating a t(11;14)(q13;q32) chromosomal rearrangement. Our results show that Southern blot analysis is helpful to identify CC/IDL, but multiple breakpoints are present over a large region, and therefore, many probes are necessary to cover all breakpoints. PMID- 8364908 TI - Oxidative damage of nuclear DNA in liver of rats exposed to psychological stress. AB - Male Sprague-Dawley rats were exposed to conditioned emotional stimuli in a communication box, which is much more psychologically conditioned stress than the commonly used restraint and water immersion, to investigate the induction of oxidative DNA damage by psychological stress. Significantly higher levels of 8 hydroxy-2'-deoxyguanosine in rat liver nuclear DNA than in the controls [1.46 +/- 0.19 (SD) 8-hydroxy-2'-deoxyguanosine/10(5) deoxyguanosine] were detected immediately after the second (1.90 +/- 0.27, P < 0.01), third (3.10 +/- 0.94, P < 0.01), and fourth exposure (2.95 +/- 1.17, P < 0.01) to conditioned emotional stimuli. This is the first evidence that oxidative damage to nuclear DNA is induced by psychological stress. PMID- 8364909 TI - Loss of a p53-associated G1 checkpoint does not decrease cell survival following DNA damage. AB - Cell cycle checkpoints regulate progression through the cell cycle. In yeast, loss of the G2 checkpoint by mutation of the rad9 gene results in increased genetic instability as well as increased sensitivity to ionizing radiation. In contrast, comparing clonogenic survival of cells which are isogeneic except for p53 functional status, we find that loss of a G1 checkpoint in mammalian cells is not associated with increased sensitivity to the lethal effects of ionizing radiation or a topoisomerase I inhibitor, camptothecin. These results indicate that increased sensitivity to DNA-damaging agents is not necessarily a defining feature of a mammalian cell cycle checkpoint. Furthermore, in light of a recent link of p53 function to radiation-induced apoptosis in hematopoietic cells, these observations suggest that p53-dependent apoptosis is a cell type-specific phenomenon and thus predict that the biological consequences of loss of p53 function will be cell type specific. PMID- 8364910 TI - IA-1, a new marker for neuroendocrine differentiation in human lung cancer cell lines. AB - IA-1 is a recently isolated novel complementary DNA which encodes a protein of 510 amino acids that contains both a zinc finger DNA-binding domain and a putative prohormone domain. mRNA expression of IA-1 has been found thus far only in tumors of neuroendocrine origin. In this report we describe the expression of IA-1 mRNA in a panel of 64 human lung cancer cell lines. IA-1 mRNA was detected by Northern blot analysis in 97% (30 of 31) of small cell lung cancer cell lines. In contrast, IA-1 mRNA was detected in only 13% (4 of 30) of non-small cell lung cancer cell lines. Nine of the 30 (30%) expressed either chromogranin A mRNA or produced L-dopa decarboxylase. Four of these 9 (44%) had detectable levels of IA 1 mRNA. In most of the lung cancer cell lines examined, IA-1 showed high concordance with the other neuroendocrine markers, L-dopa decarboxylase, and chromogranin A. The one exception was a variant small cell lung cancer cell line which expressed low or nondetectable levels of L-dopa decarboxylase. IA-1 is a candidate marker of neuroendocrine differentiation of human lung tumors. PMID- 8364911 TI - Nickel induces a signature mutation for oxygen free radical damage. AB - We have determined the specificity of mutations produced by nickel(II), a known human carcinogen, in a forward mutation assay and also used a sensitive reversion assay to show that Ni(II), like iron and copper, can produce tandem double CC- >TT mutations, a hallmark of damage to DNA by either UV irradiation or oxygen free radicals. A reduction in mutation frequencies by the addition of oxygen radical scavengers also supports the involvement of reactive oxygen species in DNA damage and mutagenesis by Ni(II). Mutagenesis by Ni(II) is enhanced by the addition of both hydrogen peroxide and a tripeptide glycyl-glycyl-L-histidine. The enhancement of mutagenesis of Ni(II) by the tripeptide indicates that these complexes could serve to localize Ni(II) in nuclei and mediate DNA damage and mutagenesis via the generation of short-lived oxygen free radicals. These data suggest that Ni(II) carcinogenesis may proceed via the generation of active oxygen species and furthermore provide a model for nickel carcinogenesis based on the binding of Ni(II) to nuclear proteins. PMID- 8364912 TI - Growth inhibition of human lung cancer cell lines by interleukin 6 in vitro: a possible role in tumor growth via an autocrine mechanism. AB - It has been considered that growth of human lung cancer cells, like other malignant cells, is positively and negatively regulated by a variety of growth factors via autocrine as well as paracrine mechanisms. The autocrine mechanism is considered to be important in the autonomy of proliferation of cancer cells. Recently, the role of autocrine growth-inhibiting factors such as transforming growth factor beta attracts special attention for better understanding of growth regulation of malignant cells. Here, we have demonstrated that a multifunctional cytokine interleukin 6 (IL-6) had an inhibitory effect on the proliferation of human non-small cell lung cancer cell lines, as shown by the growth accelerating effect of the specific anti-IL-6 antibody as well as the effect of exogenously added IL-6. Moreover, IL-6 can be expressed and released by human lung cancer cells, and these cells had specific IL-6 receptors on their cell surfaces, suggesting an autocrine mechanism. The growth-inhibitory effect of IL-6 was additive to that of transforming growth factor beta, and could not be neutralized by the addition of anti-transforming growth factor beta antibody. These results suggested that IL-6 may function as another class of autocrine growth-inhibiting factor in the growth regulation of human lung cancer. Relatively lower IL-6 sensitivity of these cells than noncarcinogenic human bronchial epithelial cells also suggested that escape from growth regulation by inhibitory factors such as IL-6 could be involved in lung cancer oncogenesis. PMID- 8364913 TI - Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon. AB - Previous work from this laboratory established that caffeic acid esters, present in the propolis of honey bee hives, are potent inhibitors of human colon tumor cell growth, suggesting that these compounds may possess antitumor activity against colon carcinogenesis. The present study was designed to investigate (a) the inhibitory effects of methyl caffeate (MC) and phenylethyl caffeate (PEC) on azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine protein kinase (TPK), and arachidonic acid metabolism in liver and colonic mucosa of male F344 rats, (b) the effects of caffeic acid, MC, PEC, phenylethyl-3-methylcaffeate (PEMC), and phenylethyl dimethylcaffeate (PEDMC) on in vitro arachidonic acid metabolism in liver and colonic mucosa, and (c) the effects of PEC, PEMC, and PEDMC on AOM-induced aberrant crypt foci (ACF) formation in the colon of F344 rats. At 5 weeks of age, groups of animals were fed diets containing 600 ppm MC or PEC (biochemical study) or 500 ppm PEC, PEMC, or PEDMC (ACF study). Two weeks later, all animals except the vehicle-treated groups were given s.c. injections of AOM, once weekly for 2 weeks. The animals intended for the biochemical study were sacrificed 5 days later and colonic mucosa and liver were analyzed for ODC, TPK, lipoxygenase, and cyclooxygenase metabolites. The animals intended for the ACF study were sacrificed 9 weeks later and analyzed for ACF in the colon. The results indicate that the PEC diet significantly inhibited AOM-induced ODC (P < 0.05) and TPK (P < 0.001) activities in liver and colon. The PEC diet significantly (P < 0.001) suppressed the AOM-induced lipoxygenase metabolites 8(S)- and 12(S)-hydroxyeicosatetraenoic acid (HETE). The animals fed the MC diet exhibited a moderate inhibitory effect on ODC and 5(S)-, 8(S)-, 12(S)-, and 15(S) HETEs and a significant (P < 0.001) effect on colonic TPK activity. However, the MC and PEC diets showed no significant inhibitory effects on cyclooxygenase metabolism. In an in vitro study, caffeic acid and MC showed inhibitory effects on HETE formation only at a 100 microM concentration, whereas PEC, PEMC, and PEDMC suppressed in vitro HETE formation in a dose-dependent manner. AOM-induced colonic ACF were significantly inhibited in the animals fed PEC (55%), PEMC (82%), or PEDMC (81%). The results of the present study indicate that PEC, PEMC, and PEDMC, present in honey, inhibit AOM-induced colonic preneoplastic lesions, ODC, TPK, and lipoxygenase activity, which are relevant to colon carcinogenesis. PMID- 8364915 TI - Reduction in the expression of glucose transporter protein GLUT 2 in preneoplastic and neoplastic hepatic lesions and reexpression of GLUT 1 in late stages of hepatocarcinogenesis. AB - Expression of two important glucose transporter proteins, GLUT 2 (which is the typical glucose transporter in hepatocytes of adult liver) and the erythroid/brain type glucose transporter GLUT 1 (representing the typical glucose transporter in fetal liver parenchyma), was studied immunocytochemically during hepatocarcinogenesis in rats at different time points between 7 and 65 wk after cessation of 7-wk administration of 12 mg/kg of body weight of N nitrosomorpholine p.o. (stop model). Foci of altered hepatocytes excessively storing glycogen (GSF) and mixed cell foci (MCF) composed of both glycogenotic and glycogen-poor cells were present at all time points studied. Seven wk after withdrawal of the carcinogen, GSF were the predominant type of focus of altered hepatocytes. Morphometrical evaluation of the focal lesions revealed that the number and volume fraction of GSF increased steadily until Wk 65. MCF were rare at 7 wk, increased slightly in number and size until Wk 37, but showed a pronounced elevation in their number and volume fraction from Wk 37 to Wk 65. In both GSF and MCF, GLUT 2 was generally decreased or partially absent at all time points. Consequently, foci of decreased GLUT 2 expression showed a steady increase in number and volume fraction from Wk 7 to Wk 65. GLUT 1 was lacking in GSF but occurred in some MCF from Wk 50 onward. The liver type glucose transporter GLUT 2 was decreased in all adenomas and hepatocellular carcinomas (HCC). In three of seven adenomas and 10 of 12 carcinomas, expression of GLUT 1 was increased compared with normal liver parenchyma. In two cases of adenoid HCC, cells of ductular formations coexpressed GLUT 2 and GLUT 1. In contrast, normal bile ducts, bile duct proliferations, and cystic cholangiomas expressed only GLUT 1. Seven of 12 HCC contained many microvessels intensely stained for GLUT 1, a phenomenon never observed in normal liver. Whenever adenoid tumor formations occurred, GLUT 1-positive microvessels were located in the immediate vicinity of these formations. Only in one HCC were such microvessels found in the absence of adenoid formations. Our studies indicate that a reduction of GLUT 2 expression occurs already in early preneoplastic hepatic foci and is maintained throughout hepatocarcinogenesis, including benign and malignant neoplasms. Reexpression of GLUT 1, however, appears in a few MCF and in the majority of adenomas and carcinomas. PMID- 8364916 TI - Interaction between ultraviolet A and ultraviolet B radiations in skin cancer induction in hairless mice. AB - The rate of tumor induction by UV-A radiation rises more slowly with time and accumulated dose than that by UV-B radiation. It has recently been shown that this difference disappears when frank papillomas are excluded from the analysis. Thus, the rate of development of "nonpapillomas" (mainly squamous cell carcinomas and precursors) can be fully characterized by a typical tumor induction time, e.g., the time until 50% of the mice bear tumors. This has opened the possibility to investigate how UV-A and UV-B exposures add up in the induction of squamous cell carcinomas, which is an important issue in risk assessments of artificial UV A sources for cosmetic or medical purposes. We present the results of an experiment in which 6 groups of 24 albino SKH:HR1 mice were treated daily for 600 days with either effective UV-A radiation, effective UV-B radiation, or combinations of both. The observed times it took for 50% of the mice to bear tumors in the combination groups were compared with those calculated on the basis of arithmetical addition of effective UV-A and effective UV-B doses. We did not find a statistically significant (P < 0.05) deviation from additivity. PMID- 8364917 TI - Induction of renal pelvic carcinoma by phenacetin in hydronephrosis-bearing rats of the SD/cShi strain. AB - Carcinogenicity of phenacetin (PH) to the urinary tract was tested with the use of spontaneously hydronephrosis-bearing rats. In Experiment 1, 55 SD/cShi male rats were fed with 2% PH-containing diet for 85 weeks, and 32 SD/cShi male rats fed basal diet for 85 weeks served as controls. Forty-three of 53 rats fed with PH had renal pelvic carcinoma with lung metastases in three. The mean induction time was 78 weeks. Ureteral carcinoma and urinary bladder carcinoma were observed in 2 and 6 of 53 rats given PH, respectively. No urinary tract carcinoma was found in control animals. In Experiment 2, early lesions of the kidney affected by PH were also evaluated with the use of SD/cShi and Sprague-Dawley (SD) rats. Two groups of animals containing 6 SD/cShi or 6 SD male rats per group were fed 2% PH-containing diet for 8 weeks. Control animals containing 6 SD/cShi rats or 6 SD rats were fed basal diet for 8 weeks. Simple hyperplasia was found in 5 of 6 SD/cShi rats given PH and 2 of 6 SD/cShi control rats. Papillary necrosis was seen in 4 of 6 SD/cShi and 2 of 6 SD rats given PH. SD/cShi rats, especially those treated with PH, showed higher but not significant 5-bromo-2'-deoxyuridine labeling indices in the covering epithelium of the renal pelvis and papillae. In this short term experiment PH and its metabolites, N-hydroxyphenacetin and N acetyl-p-aminophenol, were measured in urine and plasma by using high performance liquid chromatography. Significantly higher PH and slightly higher metabolites were detected in urine and plasma of SD/cShi rats compared to SD rats. These results indicated that the renal pelvis of SD/cShi rats had more sensitivity to PH carcinogenicity. This paper provides experimental proof of PH carcinogenicity toward the renal pelvis in an animal model. PMID- 8364914 TI - Expression of mutated p53 occurs in tumor-distant epithelia of head and neck cancer patients: a possible molecular basis for the development of multiple tumors. AB - As in most other tumor types, expression of mutated or phenotypically altered p53 is a common occurrence in head and neck carcinogenesis. Since the prognosis for many head and neck tumor patients is severely affected by the occurrence of multiple primary and secondary tumors, we have analyzed the phenotype and genotype of p53 in squamous and respiratory epithelia either adjacent to or at significant distance from the primary tumors. Many tumor patients showed multifocal overexpression of the p53 protein in a variety of these epithelia. Overexpression of p53 correlated with increased proliferation and dedifferentiation, as demonstrated by immunohistochemistry and in situ hybridization using histone H3 and cytokeratin-specific probes. Polymerase chain reaction-single-strand conformation polymorphism analysis and sequencing of p53 DNA, amplified from these biopsies after immunostaining and microdissection, confirmed and extended these findings. We have identified different mutations in p53 in different tumor-distant epithelia from the same patients. The data indicate that mutation of p53 is an early event in head and neck carcinogenesis, preceding signs of overt neoplasia, and that different mutations in p53 in multiple foci may provide a molecular basis for the development of multiple tumors. PMID- 8364918 TI - Effects of steroid hormones and opioid peptides on the growth of androgen responsive Shionogi carcinoma (SC115) cells in primary culture. AB - We investigated the effects of dihydrotestosterone (DHT), hydrocortisone (HC), basic fibroblast growth factor (bFGF), and opioid peptides on the growth of cells from the androgen-responsive Shionogi mouse mammary carcinoma (SC115) in primary culture. Androgen-responsive SC115 tumor cells were stimulated to grow in response to DHT, HC, and bFGF in a dose-responsive manner in both serum containing and serum-free media. Moreover, anti-bFGF antibody had a marked inhibitory effect on DHT- and bFGF-induced growth. Three opioid agonists, beta endorphin (beta-EP), cyclazocine, and morphine sulfate, markedly inhibited SC115 tumor cell growth at concentrations ranging from 10(-11) to 10(-7) M in serum containing medium with or without DHT, HC, or bFGF, with the greatest inhibition occurring in medium with DHT. In serum-free medium, beta-EP had no inhibitory effects on cell growth. However, beta-EP at concentrations of 10(-9) M or greater significantly inhibited cell growth in serum-free medium containing DHT, HC, or bFGF, with the greatest inhibition again occurring in medium with DHT. Naloxone (10(-8) and 10(-6) M), an opioid receptor antagonist, blocked the inhibitory effects of beta-EP and morphine sulfate. These results suggest that SC115 tumor cells in primary culture are stimulated to grow in a dose-responsive manner by DHT, HC, or bFGF in both serum-containing and serum-free media. It appears that bFGF may mediate, at least partially, DHT-stimulated cell growth. In addition, the opioid peptide system may be involved in regulating endocrine control of growth of the androgen-responsive SC115 carcinoma. The dose-responsive inhibitory effects of opioids and their reversal by naloxone suggest that these effects may be mediated by opioid receptors. PMID- 8364919 TI - Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. AB - Antioxidant micronutrients, including vitamin E, vitamin C, the carotenoids, and selenium, defend the body against free radicals and reactive oxygen molecules, suggesting a potential for these dietary components in cancer prevention. To investigate whether high intakes of antioxidant micronutrients protect against colon cancer in humans, we analyzed data from a prospective cohort study of 35,215 Iowa women aged 55-69 years and without a history of cancer who completed a dietary questionnaire in 1986. Through 1990, 212 incident cases of colon cancer were documented. Adjusted for age, total vitamin E intake was inversely associated with the risk of colon cancer (P for trend < 0.0001); the relative risk for the highest compared to the lowest quintile was 0.32 [95% confidence interval (95% CI) 0.19, 0.54]. Further adjustment for total energy intake and other risk factors in proportional hazards regression had little effect on these estimates. The association was not uniform across age groups: the multivariate relative risk of colon cancer for the highest compared to the lowest quintile of total vitamin E intake was 0.16 (95% CI 0.04, 0.70) for those 55-59 years old, 0.37 (95% CI 0.12, 1.16) for those 60-64 years old, and 0.93 (95% CI 0.27, 3.25) for those 65-69 years old. Multivariate-adjusted relative risks among women with higher total intakes of vitamins A and C and beta-carotene, and among users of selenium supplements, were not significantly different from 1.0. These prospective data provide evidence that a high intake of vitamin E may decrease the risk of colon cancer, especially in persons under 65 years of age. PMID- 8364920 TI - Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma. AB - A bovine serum albumin-conjugated doxorubicin via the glutaraldehyde bridge (BSA DXR conjugate) showed potent dose-dependent inhibition of cell growth against daunorubicin-resistant AH66 (AH66DR) cells as well as parental AH66 (AH66P) cells in vitro as compared to treatment with DXR or BSA-glutaraldehyde conjugate without DXR (BSA-GA). In the culture of AH66DR with BSA-DXR conjugate, drug accumulation in the AH66DR cells increased as a function of time up to 24 h reaching approximately the same drug level as AH66P cells treated with DXR. The intracellular accumulation of the BSA-DXR conjugate was inhibited by the addition of ammonium chloride, while that of DXR alone was not inhibited. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate or pharmacologically active DXR adduct remained in the cells at a relatively high concentration over a 36-h time period. The life-prolonging effect of the conjugate was assessed using rats inoculated i.p. with AH66P or AH66DR. The rats were treated with the BSA-DXR conjugate, DXR, a mixture of DXR with BSA, or BSA GA by either the i.p. or i.v. route. Treatment with DXR had no significant surviving effect as compared to that with saline in AH66P-bearing rats. By contrast, BSA-DXR conjugate showed a significant life-prolonging effect as compared with DXR alone in the same degree both in AH66P- and AH66DR-bearing rats. BSA-GA did not show any toxicity in vivo as well as in vitro. These results indicate that the BSA-DXR conjugate allows DXR to escape from the multidrug resistance mechanism. PMID- 8364921 TI - Locus of the interaction among 5-fluorouracil, leucovorin, and interferon-alpha 2a in colon carcinoma cells. AB - Prior studies from these laboratories demonstrated 3.2-fold potentiation of 5 fluorouracil (FUra) cytotoxicity by recombinant human interferon-alpha 2a (rIFN alpha 2a) in GC3/cl colon adenocarcinoma cells that was significantly enhanced to 14-fold when FUra was combined with rIFN-alpha 2a + a mixture of the diasteroisomers of the biologically active (6S) and inactive (6R) leucovorin or 5 formyl-H4PteGlu (LV), events that were reversible by thymidine (dThd). In GC3/clTS-c3/c3 cells, deficient in thymidylate synthase, rIFN-alpha 2a cytotoxicity was not influenced by the concentration of dThd, indicating no direct effect at the level of dThd-less stress. Direct assays of thymidylate synthase indicated no significant difference between FUra-induced accumulation of total thymidylate synthase or free or unbound thymidylate synthase in cells receiving FUra + modulators. In addition, the cytotoxic activity of CB3717, a specific quinazoline-based inhibitor of thymidylate synthase, was not potentiated by rIFN-alpha 2a. These studies suggested that thymidylate synthase was not the primary target site for rIFN-alpha 2a activity. Since data indicated that a 5 fluoropyrimidine was required in the interaction among FUra, LV, and rIFN-alpha 2a, attention was focused at the level of DNA. Both DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) induced by FUra were significantly elevated by rIFN-alpha 2a and LV administered as single modulators and were influenced by the concentrations of both FUra and rIFN-alpha 2a. However; when FUra was combined with LV, rIFN-alpha 2a further potentiated the frequency of DNA SSBs, and data correlated with the relative cytotoxic activity of FUra-LV-rIFN alpha 2a combinations. No effect on CB3717-induced DNA SSBs or DSBs by rIFN-alpha 2a was demonstrated. Drug exposure for 48 h was required to detect measurable differences in DNA SSB frequency among FUra-LV-rIFN-alpha 2a treatment groups and correlated with decreased clonogenic survival under these conditions. Continuous exposure to FUra (72 h) allowed shorter exposures to LV and/or rIFN-alpha 2a (48 h) to maintain maximal cytotoxicity. Shorter exposure times for FUra during continuous exposure to the modulators were less cytotoxic. Data suggest that the primary locus of the interaction among FUra, LV, and rIFN-alpha 2a lies at the level of DNA. rIFN-alpha 2a may exert its effects via enhancement of FUra base excision or incorporation into DNA, events that subsequently become influenced by thymidylate synthase inhibition and dThd-less stress and are further potentiated by LV.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364922 TI - Effects of temperature on the therapeutic efficacy and pharmacokinetics of ifosfamide. AB - The influence of tumor temperature (28, 32, 37, 39, 41, or 43 degrees C for 1 h) on the therapeutic efficacy of i.v. single bolus injections of ifosfamide (IFO) (32, 65, 125, or 250 mg/kg body weight) in human tumor xenografts (MX1 breast carcinoma) grown in nude mice (n = 240) was studied. Tumor temperature was controlled by water bath immersion. Sixty days after treatment the percentage of tumor-free survival was determined. For example, at 37 degrees C IFO in a dose of 65 mg/kg body weight led to 10% tumor-free survival in the treated animals. At 43 degrees C the same dose resulted in 60% tumor-free survival. A clear drug dose- and temperature-dependent increase of the therapeutic efficacy of an active oxazaphosphorine compound was also demonstrated in vitro. The concentrations of IFO and of 4-hydroxyifosfamide in blood and tumors at different body temperatures (controlled by water bath immersion) were determined over 120 min and WBC counts were obtained. The half-lives and the areas under the curve for IFO in blood were not significantly different at 37 degrees C and 41 degrees C. Since the half-life of IFO depends mainly on hepatic metabolism, the similarity of half-lives and of areas under the curve for IFO at 37 degrees C and 41 degrees C indicates a constant activation rate. However, significantly lower plasma concentrations of the activated drug at a liver (body) temperature of 41 degrees C, compared with 37 degrees C, were found, indicating a higher elimination rate. The concentration of the activated drug in the tumors within the initial 60 min at 41 degrees C, however, exceeded by > 2-fold that at 37 degrees C. The bone marrow toxicity of the same drug dose did not significantly increase with body temperature. PMID- 8364923 TI - Antitumor protection from the murine T-cell leukemia/lymphoma EL4 by the continuous subcutaneous coadministration of recombinant macrophage-colony stimulating factor and interleukin-2. AB - Combined continuous s.c. coadministration of macrophage-colony stimulating factor (M-CSF) plus interleukin-2 (IL-2) by osmotic pump protected mice given i.v. injections of a lethal dose of EL4 T-cell leukemia/lymphoma. Antitumor protection was significantly greater than that afforded by treatment with either cytokine alone. Since neither IL-2 receptors nor M-CSF receptors were expressed on EL4, the antitumor effect was likely attributed to murine effector cells. To determine how M-CSF+IL-2 provided this effect, we performed immunophenotypic and functional analyses as well as in vivo depletion studies of putative antitumor effector cells. Splenic phenotyping experiments revealed that the highest levels of macrophages and natural killer cells were observed in mice given the cytokine combination rather than either M-CSF or IL-2 alone. In vivo depletion of natural killer cells ablated the antitumor protective effect of M-CSF and IL-2. T-cells were also important for M-CSF+IL-2 efficacy, since adult thymectomy/T-cell depletion significantly inhibited the ability of cytokine coadministration to protect against EL4. Coadministration of the 2 cytokines significantly elevated in vivo levels of CD3+CD4+, CD3+CD8+, CD3+NK1.1+ T-cells, and CD3+CD25+ (activated) T-cells, and elevated anti-EL4 cytotoxic T-cell activity measured in vitro. Although WBC counts and fluorescence-activated cell sorter studies showed that M-CSF+IL-2 treatment significantly elevated neutrophils, s.c. delivery of granulocyte-colony stimulating factor at doses sufficient to induce neutrophilia was unable to confer anti-EL4 protection. These studies indicate that macrophages, T-cells, and natural killer cells are all important in the M-CSF+IL 2 anti-EL4 response. The superior antitumor effect of this cytokine combination along with the ability of M-CSF to diminish the toxicity of IL-2 in this model suggests that further investigations into the clinical potential of this combination treatment are warranted. PMID- 8364924 TI - Prolonged depletion of O6-methylguanine DNA methyltransferase activity following exposure to O6-benzylguanine with or without streptozotocin enhances 1,3-bis(2 chloroethyl)-1-nitrosourea sensitivity in vitro. AB - This study was undertaken to ascertain the importance of prolonged depletion of O6-methylguanine DNA methyltransferase (MGMT) activity, following O6 benzylguanine (BG) and streptozotocin (STZ) exposure, in reversing 1,3 bis(2 chloroethyl)-1-nitrosourea (BCNU) resistance in vitro. We evaluated BCNU-induced cytotoxicity and measured the temporal recovery of MGMT activity in human colon carcinoma HT-29 cells following treatment with BG, STZ, or the combination of BG and STZ. The pretreatment regimens which provided the greatest potentiation of BCNU cytotoxicity were those exhibiting the greatest temporal inhibition of MGMT activity. The combination of BG (10 microM) and STZ (1.0 mM) produced sustained inhibition of MGMT activity through 24 h and potentiated BCNU cytotoxicity by at least one log greater than either agent alone. Similarly, BG (10-100 microM) produced marked reductions in MGMT activity and increased BCNU cytotoxicity in a dose-dependent fashion. A 100-microM dose of BG inhibited MGMT activity for 48 h and potentiated BCNU induced cell kill by 3 logs greater than BCNU alone. In addition, we observed that during the period of sustained inhibition of MGMT activity, no changes in the steady-state MGMT mRNA levels occurred. We conclude that prolonged inhibition of MGMT activity is an important determinant in reversing BCNU resistance and that chemotherapeutic regimens targeting the inactivation of MGMT activity should be optimized such that MGMT activity is depleted for at least 24 h following BCNU administration. PMID- 8364925 TI - Etoposide-induced cytotoxicity in two human T-cell leukemic lines: delayed loss of membrane permeability rather than DNA fragmentation as an indicator of programmed cell death. AB - Features of the apoptotic response evident in glucocorticoid-treated thymocytes are not uniformly observed in cell lines exposed to anticancer drugs. The significance of such variation has been assessed by monitoring molecular and cellular processes induced by etoposide (VP-16) in the human lymphoblastoid T cell lines CCRF-CEM (CEM) and MOLT-4 contrasted, where appropriate, with those induced by necrotizing injury. Cytotoxic concentrations of the drug were determined to be 5-100 microM on the basis of tetrazolium reduction assay. The two lines were equally sensitive to VP-16; no difference in concentration of drug which inhibited cell growth by 50% with respect to control (i.e., drug free) cultures was apparent irrespective of exposure times from 3-72 h. DNA strand breaks were evident in both populations within 3 h of exposure to VP-16. Morphological change, assessed microscopically, involving nuclear condensation and cell shrinkage was qualitatively and quantitatively similar in VP-16-treated CEM and MOLT-4 cells. Flow cytometric analysis indicated that the G2/M fraction of the randomly dividing MOLT-4 population was approximately one-third that of CEM cells, but each line exhibited a decrease in this fraction 3-6 h after treatment. Despite these similarities, marked differences in the response to VP 16 were evident in the two populations. Internucleosomal fragmentation, detected electrophoretically 3 h after treatment in DNA isolated from CEM cells, was not detected under any condition in MOLT-4 DNA. Apoptotic bodies, also evident within 3 h of VP-16 treatment of CEM cells, were not readily apparent in MOLT-4 cells under the same conditions. Treatment causing necrosis resulted in trypan blue uptake within 1 h in a similar high proportion of cells from both lines. Exposure to VP-16 resulted in such a loss of membrane integrity by 6 h in CEM cells, while change in this parameter occurred only after 24 h in the case of MOLT-4 cells. The findings indicate a wide scope of difference in apoptotic response and suggest delayed loss of membrane permeability, rather than DNA fragmentation, as the clearest indicator of programmed cell death in these populations. PMID- 8364926 TI - Cross-reactivity of anti-CD3/IL-2 activated effector cells derived from lymph nodes draining heterologous clones of a murine tumor. AB - Cells from lymph nodes (LN) draining progressively growing tumors can differentiate into immune effector cells upon in vitro stimulation with anti-CD3 monoclonal antibodies followed by interleukin-2. The adoptive transfer of these activated LN cells to tumor-bearing mice mediates potent tumor-specific therapeutic effects. In this study, we sought to further characterize the antitumor efficacy and specificity mediated by the anti-CD3/IL-2 activated tumor draining LN cells against heterologous clones derived from the murine MCA 106 sarcoma. Ten clones of divergent characteristics with regard to morphology, in vivo growth rate, ability to establish pulmonary metastases, MHC class I (H-2) antigen expression, susceptibility to lysis by allogeneic cytotoxic T lymphocytes, as well as sensitivity to doxorubicin were selected and analyzed. In adoptive immunotherapy experiments, pulmonary metastases derived from each clone were found to be sensitive to the therapeutic effects of activated cells derived from LN draining the parental MCA 106 tumor. The antigenic cross-reactivity was evident from the observation that activated cells from LN draining each of the individual tumor clones were capable of mediating the regression of parental tumor metastases. The specificity of the antitumor reactivities mediated by LN cells draining MCA 106 clones was demonstrated by a lack of in vivo efficacy against metastases derived from the antigenically distinct MCA 205 sarcoma. Additionally, selected clones were tested for their ability to stimulate draining LN against other cloned tumors or used as targets for therapy with activated LN cells draining different clones. In all 29 adoptive immunotherapy experiments, there was complete cross-reactivity between different MCA 106 tumor clones. These findings suggest that the MCA 106 tumor-specific antigen(s) that stimulates draining LN in vivo and recognized by the anti-CD3/IL-2 activated cells is present on most if not all tumor cells. However, in the absence of a demonstrably resistant tumor clone, a very highly polymorphic antigen with many cross reactive, but distinct epitopes might be operative and attributable to these observations. PMID- 8364927 TI - Blockade of epidermal growth factor receptor function by bivalent and monovalent fragments of 225 anti-epidermal growth factor receptor monoclonal antibodies. AB - We have previously described anti-epidermal growth factor (EGF) receptor monoclonal antibodies (MAbs) which can block binding of transforming growth factor alpha (TGF-alpha) and EGF to receptors and inhibit activation of receptor tyrosine kinase. Studies with these MAbs involving cell cultures and nude mouse xenografts demonstrated their capacity to inhibit the growth of a variety of tumor cell lines, which express EGF receptors and TGF-alpha and appear to depend upon receptor activation for cell proliferation. To explore the mechanism(s) by which anti-EGF receptor 225 MAb inhibits cell proliferation, we have compared the activity of native 225 MAb with the response to bivalent 225 F(ab')2 and monovalent 225 Fab' fragments. Both native 225 MAb and its fragments could inhibit the binding of 125I-EGF to EGF receptors. Scatchard analysis revealed that the Kd of 225 F(ab')2 is comparable to that of 225 MAb (1 nM), whereas the Kd of 225 Fab' is 5 nM. Both bivalent 225 MAb and 225 F(ab')2 and monovalent 225 Fab' were able to completely inhibit TGF-alpha-induced EGF receptor tyrosine kinase activation, as assayed by autophosphorylation of tyrosine residues of EGF receptors on MCF10A nonmalignant human mammary cells, MDA468 human breast adenocarcinoma cells, and A431 human vulvar squamous carcinoma cells. The bivalent forms of MAb could inhibit proliferation stimulated by endogenous (autocrine) TGF-alpha in cultures of these three cell lines. They also blocked growth stimulation by added exogenous TGF-alpha in cultures of MCF10A cells and the growth-inhibitory effect of exogenous TGF-alpha upon MDA468 and A431 cell cultures. Monovalent 225 Fab' had weaker inhibitory effects upon the proliferation of these cell lines. To determine whether the in vivo antiproliferative activity of anti-EGF receptor MAb can occur without the participation of the Fc portion of MAb, the capacities of 225 F(ab')2 and native 225 MAb to inhibit growth of s.c. A431 cell xenografts were compared. Equimolar amounts of either 225 MAb or 225 F(ab')2 were administered at intervals equivalent to the half-lives of the molecules, to attempt to maintain comparable plasma levels. Both 225 MAb and 225 F(ab')2 inhibited A431 cell xenograft growth in a dose-dependent manner, with a more sustained response in the case of the intact antibody.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364928 TI - Collaboration between growth factors and diverse chemical carcinogens in hepatocarcinogenesis of transforming growth factor alpha transgenic mice. AB - Transforming growth factor alpha (TGF-alpha) has been shown to induce liver tumors within 1 year in transgenic male mice in which this potent mitogen is overexpressed. To determine more precisely how TGF-alpha participates in multistep tumorigenesis of the liver, genotoxic (diethylnitrosamine or dimethylnitrosamine) and nongenotoxic (phenobarbital) chemical carcinogens were administered independently to TGF-alpha transgenic mice [line MT42 on a Crl:CD 1(ICR)BR background]. TGF-alpha overexpression dramatically accelerated carcinogen-induced hepatocarcinogenesis in MT42 males but not females. Interestingly, all three chemical agents were found to enhance strongly both hepatic tumor formation and progression in TGF-alpha transgenic male mice. In this study 100%, 90%, and 78% of transgenic males exposed to diethylnitrosamine, dimethylnitrosamine or phenobarbital, respectively, developed tumors between 24 and 32 weeks of age. Moreover, approximately 70% of tumor-bearing transgenic mice from each treatment group had hepatocellular carcinomas; no malignant lesions were found in any carcinogen-treated or untreated nontransgenic mice or in untreated MT42 mice at this age. These results demonstrate that chemical agents as diverse as nitrosamines and phenobarbital act as cocarcinogens with TGF-alpha in the livers of these transgenic mice, indicating that TGF-alpha possesses the unique ability to complement both initiation and promotion in hepatocarcinogenesis. Furthermore, because carcinogen-induced malignant conversion was restricted to transgenic mice, constitutive TGF-alpha overexpression may promote liver tumor progression as well. PMID- 8364929 TI - Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. AB - Detailed cytogenetic analyses were carried out on primary tumor specimens and cell lines from 23 patients with pleural malignant mesothelioma (MM). Clonal abnormalities were identified in 20 of 23 MM. In 3 cases, karyotypic data were compiled from harvests of both short-term cultures (1-3 days), and primary cultures grown on murine feeder layers for several weeks. The karyotypes obtained with these 2 different culture methods were very similar, although polyploid versions of abnormal clones were found only in the long-term cultures. In addition, while short-term cultures from 9 tumor biopsies usually exhibited near diploid clones, cell lines derived from 11 tumors tended to have higher ploidies. Each of the cytogenetically abnormal MM displayed multiple clonal alterations. The 2 most frequent changes were chromosomal losses of specific regions in 1p (17 cases) and 9p (16 cases). The shortest regions of overlap of these losses were at 1p21-p22 and 9p21-p22, respectively. Other common abnormalities included losses of 3p21 (13 cases) and 6q15-q21 (9 cases), and numerical losses of chromosomes 14, 16, 18, and 22 (each observed in 10-13 tumors). In many of the MM examined, most or all of these recurrent changes occurred in combination, suggesting the involvement of a pathogenetic cascade in this cancer. The pattern of recurrent chromosomal losses suggests that these regions represent the locations of tumor suppressor genes whose loss/inactivation may have a pivotal role in MM tumorigenesis. PMID- 8364930 TI - Loss of heterozygosity in familial breast carcinomas. AB - Three loci have been implicated in the etiology of familial breast cancer; the BRCA1 locus on 17q, the p53 gene on 17p, and the androgen receptor gene on the X chromosome. However, it has been estimated that in approximately 50% of all breast cancer families the predisposing genetic defect is not linked to any of these three loci. In an attempt to identify chromosomal regions harboring putative breast cancer genes we performed allelotyping in 82 familial breast carcinomas. Polymorphic markers representing 45 different loci were analyzed and the most frequently involved chromosomal arms were 8p, 16q, 17p, 17q, and 19p. PMID- 8364931 TI - A codon 248 p53 mutation retains tumor suppressor function as shown by enhancement of tumor growth by antisense p53. AB - Codon 248 in domain iv of the highly conserved region of the p53 gene is a frequent site of mutations associated with sporadic cancers and the familial cancer syndrome (Li-Fraumeni syndrome). Therefore, a characterization of the functional significance of a codon 248 mutation is of interest. We used antisense RNA methodology to study the role of the wild-type and mutated p53 gene in cell growth and tumorigenesis. We introduced wild-type p53 complementary DNA in sense or antisense orientation under control of a beta-actin promoter into human non small cell lung cancer cell line H322a which has a codon 248 mutation (G to T) and WTH226b which has wild type p53. The biological properties and p53 expression of stable G418-resistant clones were analyzed. We observed that in both cell lines antisense RNA expression significantly reduced p53 mRNA and protein production; it also caused increases in growth rate in cell cultures and in tumorigenicity in nu/nu mice for both cell types, suggesting that the mechanism by which p53 suppresses cell proliferation and tumorigenesis is not always abrogated by a codon 248 mutation. PMID- 8364932 TI - Monoclonal antibody FW6 defines an epitope on alpha 3/4-monofucosylated polylactosaminoglycans expressed by fetal and colon carcinoma-associated mucins. AB - A mouse IgM monoclonal antibody FW6 was established after immunization of mice with mucins from human amniotic fluid and was characterized with regard to its binding epitope. According to a series of biochemical criteria the epitope is located on O-linked neutral carbohydrates of M(r) 700,000 and M(r) 570,000 mucins in human amniotic fluid. The epitope is presumed to contain alpha 3/4-linked fucose and terminal beta 3/4-linked galactose that are labile to the fucosidase I from almond emulsion or to the galactosidase from bovine testes, respectively. Immunoreactive fractions of glycan alditols from human amniotic fluid mucins were partially characterized by fast atom bombardment-mass spectrometry and methylation analysis to be composed of monofucosylated polylactosamine-type deca- or nonasaccharides. According to antibody competition studies, inhibition assays with defined carbohydrates and binding assays on neoglycolipids monoclonal antibody FW6 are presumed to recognize a novel epitope that is distinct from known carbohydrate markers of the Lex/Ley family associated with colonic carcinomas. The selective reactivity of this monoclonal antibody to the majority of human colonic carcinomas and its nonreactivity to normal colonic mucosa may render this antibody as a valuable tool in cancer diagnosis or cancer treatment. PMID- 8364933 TI - Chemotaxis and haptotaxis of human malignant mesothelioma cells: effects of fibronectin, laminin, type IV collagen, and an autocrine motility factor-like substance. AB - A human malignant pleural mesothelioma cell line (STAV) was studied with respect to production of the extracellular matrix components laminin, type IV collagen, and fibronectin, and interactions with these proteins in vitro. We also analyzed STAV cell serum-free conditioned medium with respect to the possible presence of "autocrine motility factor-like" substance. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of biosynthetically labeled STAV serum-free conditioned medium showed that STAV cells released several proteins into the medium, including components with molecular weights of 850,000, 540,000 and 440,000. Using Western blotting we identified these proteins as laminin, type IV collagen, and fibronectin, respectively. By immunocytochemistry laminin, type IV collagen, and fibronectin were detected as a matrix surrounding the cells. Plastic culture dishes coated with microgram quantities of laminin, type IV collagen, and fibronectin induced attachment and spreading of STAV cells. Laminin, type IV collagen, and fibronectin stimulated directional (chemotactic) migration of STAV cells in Boyden chambers fitted with 8 microns filters. The same cells also migrated to insoluble step gradients of filter-bound extracellular matrix components (haptotaxis). When STAV serum-free conditioned medium was separated by using fast protein liquid chromatography Superose 6 gel filtration, two motility inducing protein peaks were detected. The first peak contained proteins with molecular weight > 220,000 that had both chemotactic and haptotactic properties, while the second peak contained material with apparent molecular weights of approximately 67,000 that had chemotactic and chemokinetic (random motility) but not haptotactic properties. Analysis of the M(r) 67,000 material indicated that it was a heat-sensitive and trypsin-digestible protein. The production of both soluble and insoluble extracellular matrix components by human mesothelioma cells and the motile response to these molecules as well as the production of a M(r) 67,000 autocrine motility factor-like substance may be important for the highly invasive motile behavior of this tumor. PMID- 8364935 TI - Increased transforming growth factor beta expression inhibits cell proliferation in vitro, yet increases tumorigenicity and tumor growth of Meth A sarcoma cells. AB - Several observations correlate increased expression of transforming growth factor (TGF) beta 1 with tumorigenesis, suggesting that expression of this multifunctional growth factor may provide an advantage in tumor formation. However, many tumor cells are inhibited in their proliferation by TGF-beta in vitro, thus suggesting that TGF-beta synthesis could exert an antiproliferative effect on tumor formation. To evaluate the physiological relevance of increased TGF-beta 1 synthesis in such tumor cells which are strongly inhibited in their proliferation by TGF-beta, we chose Meth A sarcoma cells as a model system. We established cell clones overexpressing TGF-beta 1 and determined its effect on tumor formation in mice that are not immunocompromised. Increased expression of biologically active TGF-beta 1 resulted in a profound growth inhibition in the transfected clones and increased adhesiveness in vitro. However, these cells were much more tumorigenic than Meth A cells that did not overexpress TGF-beta 1, as assessed by both tumor incidence and tumor growth. In addition, parental Meth A cells were inhibited in their tumor formation by neutralizing TGF-beta antibodies and stimulated by exogenous TGF-beta. Our results thus provide evidence that increased TGF-beta synthesis provides a major advantage for tumorigenesis, even if the cells are growth inhibited by their endogenous TGF-beta synthesis in culture. These results suggest that, in vivo, direct effects of TGF-beta on the tumor environment, such as increased extracellular matrix formation and cell matrix interactions, and local suppression of the immune surveillance may provide a growth advantage which overrules any direct antiproliferative effects of TGF beta, as suggested by the effects in culture. PMID- 8364934 TI - MAb U36, a novel monoclonal antibody successful in immunotargeting of squamous cell carcinoma of the head and neck. AB - Using viable cells of a human head and neck squamous cell carcinoma (HNSCC) cell line as immunogen, we developed monoclonal antibody (MAb) U36. Immunohistochemical examination revealed distinct surface labeling of MAb U36 with normal human squamous epithelium and squamous cell carcinomas of distinct sites of origin; head and neck, lung, esophagus, cervix, and epidermis. MAb U36 shows high affinity binding (affinity constant, 3.5 x 10(10)/M) with a cell surface antigen expressed by in vitro cultured HNSCC cell lines. Similarity of the reactivity profiles of MAb U36 and MAb E48, currently the most promising antibody described for specific targeting of HNSCC in patients, warranted further comparison of these MAbs. MAb U36 recognizes a M(r) 200,000 antigen, which is different from the MAb E48 defined antigen. Furthermore, comparison of immunohistochemical staining patterns of MAb U36 and MAb E48 on a broad panel of primary HNSCC sections revealed more extensive staining for MAb U36: more tumors showed reactivity with MAb U36 and more tumor cells per tumor showed positive reaction, and staining was found to be more intense. MAb U36 does not show cross reactivity with mouse, rat, pig, sheep, or bovine tongue epithelium. As a first approach to evaluate the suitability of MAb U36 for tumor targeting in vivo, radiolabeled MAb U36 was administered to athymic nude mice bearing human HNSCC xenografts on both flanks. Selective tumor accumulation of the radioimmunoconjugate was observed. Mean tumor uptake (in percent injected dose/g wet-weight of tissue) of MAb U36 at days 1, 2, 3, 5, 7, and 12 was 15.1, 17.9, 24.0, 21.0, 25.8, and 16.0%, respectively. The tumor to blood ratio at day 1 was 0.9 and increased up to 3.8 at day 12. The tumor uptake at day 12 was at least 10 times higher when compared to other tissues. The corollary of these findings is that MAb U36 harbors high potential for specific targeting of HNSCC. PMID- 8364936 TI - Establishment of estrogen receptor-positive transplantable rat thyroid tumor cell lines in vivo. AB - We established 17 transplantable rat thyroid tumor cell lines from the primary thyroid tumor of rats induced by N-bis(2-hydroxypropyl)nitrosamine. Among the 17 tumor cell lines established, only two of them (D1 and G1) were estrogen receptor (ER) positive. These two cell lines were characterized with respect to transplantability, histological features, ER contents and cellular localization, and expression of ER message. The ER contents, determined by dextran-coated charcoal assay, were 13.3 and 20.7 fmol/mg protein for D1 and G1 cell lines, respectively. Scatchard plot analysis indicates that the dissociation constants (Kd) were 0.17 and 0.4 nM, respectively, for D1 and G1 cell lines. Sucrose density centrifugation analysis detected a hormone-receptor complex which sedimented at the 4S region, characteristic for ER. Immunohistological staining revealed that the ER was localized in the nuclei. The presence of ER in D1 and G1 cell lines was further confirmed by reverse transcriptase-polymerase chain reaction to detect the ER mRNA. These results demonstrated that ER is expressed in some thyroid tumors. The ER-positive transplantable tumor cell lines are useful for studying the direct effect of estrogen on thyroid tumors in vitro and in vivo. PMID- 8364937 TI - Tamoxifen-induced increase in the potential doubling time of MCF-7 xenografts as determined by bromodeoxyuridine labeling and flow cytometry. AB - The anti-estrogen tamoxifen (TAM) is widely used in the therapy of human breast cancer. Shown to induce a G1 transition delay in vitro, the kinetic effects of TAM on breast carcinoma cells growing as tumor xenografts in nude mice have been less well characterized. In this study, we demonstrate a significant increase in the tumor potential doubling time (Tpot) and decrease in the labeling index (%LI) of estradiol (E2)-stimulated MCF-7 xenografts following TAM treatment or E2 deprivation. MCF-7 tumor pieces were transplanted s.c. into nude mice supplemented with Silastic capsules containing E2. After 2-4 weeks, animals were randomized to continued E2 treatment, E2 and TAM treatment, or E2 deprivation. At times ranging from 0 to 23 days after treatment, animals were given injections of bromodeoxyuridine and tumors excised for kinetic analysis. Using flow-cytometric techniques, the Tpot and %LI were estimated for all tumors. Seven independent experiments were performed and data pooled for statistical analysis. At the time of hormonal manipulation, E2-stimulated tumors had a volume doubling time of 5 days, a Tpot of 2.3 days, and a %LI of 23%. Continued E2 treatment resulted in only minimal changes in Tpot and %LI over the remainder of the observation period. Treatment with TAM resulted in a slowing of tumor growth (tumor doubling time, 12 days), a significant (P < 0.001) increase in Tpot to 6.6 days, and a decrease in %LI to 8% by 23 days posttreatment. E2 deprivation resulted in a cessation of tumor growth and similar changes in Tpot and %LI to 5.3 days and 10%, respectively (P < 0.001). In contrast to previous reports, these data demonstrate that TAM treatment and E2 deprivation both significantly decrease tumor cell proliferation in MCF-7 xenografts. PMID- 8364938 TI - A paracrine migration-stimulating factor for metastatic tumor cells secreted by mouse hepatic sinusoidal endothelial cells: identification as complement component C3b. AB - Selective malignant cell invasion at secondary sites mediated by organ-specific (paracrine) motility factors may be of importance in preferential organ colonization of metastatic cells. In this study we isolated and examined a migration-stimulating activity present in mouse hepatic sinusoidal endothelial cell-conditioned medium (HSE-CM). HSE-CM contains migration-stimulating activity for highly liver-metastatic (RAW117-H10) and highly lung- and liver-metastatic (RAW117-L17) mouse large cell lymphoma sublines but not for the poorly metastatic parental line (RAW117-P). A migration-stimulating factor for H10 cells was purified from HSE-CM by hydroxylapatite affinity and DEAE anion exchange chromatography, Sephacryl S-200 gel filtration, and preparative native gel electrophoresis. The activity in each of the purification fractions was measured in a Transwell chamber assay using 3-microns diameter pore filters. Upon sodium dodecyl sulfate polyacrylamide gel electrophoresis, the component migrated as a single component of M(r) > 200,000 (nonreducing conditions) or as two components or M(r) approximately 110,000 and approximately 67,000 (reducing conditions). The factor was bound to Concanavalin A-Sepharose but not to heparin- or gelatin Sepharose affinity columns, induced mainly H10 chemotactic cell activity and some chemokinetic activity, and preferentially stimulated the chemotaxis of liver colonizing RAW117 sublines (H10 > L17 > P). NH2-terminal amino acid sequence analysis of each subunit indicated that the HSE-CM-derived migration-stimulating factor was a proteolytic fragment of complement component C3. HSE-derived migration-stimulating factors may be important in determining the ability of RAW117 tumor cells to invade and colonize the liver. PMID- 8364939 TI - Heart transplant candidates' perception of helpfulness of health care provider interventions. PMID- 8364940 TI - Lessons learned with ambulatory blood pressure monitoring: a focus on ramipril. AB - Ambulatory blood pressure monitoring (ABPM) has been available since the mid 1970s. Widespread use of ABPM in research settings has led to an appreciation of its advantages and disadvantages. ABPM is a valuable research tool because of its ability to evaluate the duration and consistency of action with new antihypertensive agents. It has also been used to exclude patients who have white coat hypertension from pharmacotherapy. Past and current clinical studies are reviewed to illustrate the role of this technique in the development of a new angiotensin converting enzyme inhibitor, ramipril. The studies involve administering a single daily dose of ramipril to lower blood pressure and ABPM. Three double-blinded, randomized studies and one placebo-controlled, crossover study are reviewed. In these studies of patients with essential hypertension, once-daily ramipril controlled blood pressure, reduced systolic/diastolic blood pressure throughout a 24-hour period, and did not interfere with normal circadian blood pressure patterns. Lessons learned from research suggest that ABPM will find a niche in clinical practice. PMID- 8364941 TI - Efficacy and tolerability of imipenem-cilastatin versus ceftazidime plus tobramycin as empiric therapy of presumed bacterial infection in neutropenic cancer patients. AB - The efficacy and tolerability of monotherapy with imipenem-cilastatin (I-C) were compared with that of ceftazidime plus full-course therapy with an aminoglycoside (tobramycin) (C&T) in the treatment of presumed bacterial infection in neutropenic cancer patients. A total of 106 adult patients diagnosed with presumed bacterial infection and an underlying malignancy with an absolute neutrophil count (ANC) < 500/mm3 were enrolled in this open-label study. A total of 131 febrile episodes occurred. Forty-five patients in the I-C group and 41 in the C&T group, who were well matched on demographic and baseline characteristics, were evaluable for efficacy and safety. Seventy-two hours after the start of therapy, no significant between-group differences in treatment outcomes, including withdrawals or deaths, were seen. Thirty-five (78%) of 45 patients in the I-C group and 29 (71%) of the 41 in the C&T group had successful outcomes at the final evaluation. Superinfection occurred in 8 (18%) I-C patients and 3 (7%) C&T patients. Within the subgroup of patients with an initial ANC < 100/mm3, the final evaluation showed no significant differences in treatment outcome between groups. Of the 131 in the safety population 30 (46%) I-C patients and 28 (42%) C&T patients had one or more adverse experiences; drug-related adverse events occurred in 25 (38%) patients in the I-C group and 11 (17%) patients in the C&T group. The data suggest that imipenem-cilastatin should be considered for initial empiric therapy of presumed bacterial infection in neutropenic cancer patients. PMID- 8364942 TI - Pain relief after dental impaction surgery using ketorolac, hydrocodone plus acetaminophen, or placebo. AB - In a double-blind, placebo-controlled study, 207 patients with moderate pain after surgical removal of impacted third molars were randomly assigned to receive a single oral dose of 10 mg of ketorolac tromethamine, 10 mg of hydrocodone plus 1000 mg of acetaminophen, or placebo. Analgesic effect as assessed by summed pain intensity difference at 3 and 6 hours was significantly (P < or = 0.01) greater after ketorolac than after hydrocodone/acetaminophen. Total pain relief at 3 and 6 hours was significantly (P < 0.026) greater after ketorolac than after hydrocodone/acetaminophen or placebo. Patients taking hydrocodone/acetaminophen remedicated significantly (P = 0.027) sooner than those taking ketorolac. In this single-dose study, adverse events were reported more frequently by patients taking hydrocodone/acetaminophen than with ketorolac or placebo. It is concluded that, in this pain model, 10 mg of ketorolac affords better pain relief with fewer side effects than hydrocodone/acetaminophen. PMID- 8364943 TI - A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. AB - A large double-blind, vehicle-controlled study of 143 patients with chronic postherpetic neuralgia (PHN) was performed to evaluate the degree of efficacy of topically applied capsaicin 0.075% cream. In addition, the safety and efficacy of long-term application of topical capsaicin in PHN was assessed by following patients in an open-label study for up to 2 years. In the double-blind phase, 143 patients with PHN of 6 months' duration or longer were enrolled. Since epidemiologic studies of patients who receive no treatment have shown that only 10% to 25% of those with PHN after 1 month will still have pain at 1 year, two separate efficacy analyses were performed: one with all evaluable patients (n = 131) and the other with 93 patients whose PHN lasted for longer than 12 months prior to study startup. All efficacy variables, including the physician's global evaluation of reduction in PHN pain, changes in pain severity on the categoric scale, visual analogue scale for pain severity, visual analogue scale for pain relief, and functional capacity scale, showed significant improvement at nearly all time points throughout the study for both patient groups, based on duration of PHN pain. In contrast, the group receiving vehicle cream remained essentially unchanged. Data from the long-term, open-label phase (up to 2 years, n = 77), which immediately followed the 6-week blinded phase, showed that the clinical benefit in patients treated for a short (6-week) period with topical capsaicin could be maintained or amplified in most patients (86%) during prolonged therapy. There were no serious adverse effects observed or reported throughout the trial; in fact, the only side effect associated with capsaicin treatment was the burning or stinging at local sites of application (in 9% of patients) during exposures of up to 2 years (long-term phase). On the basis of these data, we conclude that capsaicin 0.075% cream is a safe and effective treatment for the pain of postherpetic neuralgia and should be considered for initial management of patients with this condition. PMID- 8364944 TI - Efficacy and tolerability of a combination of enalapril and hydrochlorothiazide in the treatment of hypertension measured manually and with an ambulatory blood pressure monitor. AB - The efficacy and tolerability of an enalapril maleate-hydrochlorothiazide combination (EM-HCTZ) were evaluated in a prospective, open-label study in 26 patients with uncomplicated essential hypertension (mean baseline sitting systolic/diastolic blood pressure: 153/103 mmHg) requiring two agents to reduce sitting diastolic blood pressure (SDBP) below 90 mmHg. Their mean age was 52 years. Patients received enalapril 5 mg daily, which was increased to 10 mg if SDBP was not reduced to < 90 mmHg during a 5-week titration period following washout. If blood pressure did not reach that goal, 25 mg hydrochlorothiazide was added. Only patients who required enalapril 10 mg and hydrochlorothiazide 25 mg for control (SDBP < 90 mmHg) at the end of titration received open-label EM-HCTZ as maintenance therapy for 6 weeks. The SDBP of 19 of the 26 patients (73%) who began titration was controlled at the end of titration, and they received maintenance therapy. During maintenance, the mean SDBP decreased from baseline 13.2 mmHg at week 2, 13.3 mmHg at week 4, and 10.1 mmHg at week 6. All changes from baseline were significant. At the end of the maintenance period, SDBP was controlled in 8 (42%) of 19 patients enrolled. One patient was withdrawn from the study because blood pressure was poorly controlled. Ambulatory blood pressure (ABP) was monitored, average outcome was computed for each patient during the 24 hour interval, and with a paired comparison, baseline and follow-up data were compared with the data measured manually. The mean baseline ABP was 9 mmHg lower than the baseline SDBP measured manually (r = 0.58, P = 0.01). Following treatment with EM-HCTZ, mean diastolic blood pressure fell 10 mmHg and mean systolic blood pressure fell 15 mmHg. In summary, EM-HCTZ was highly effective and generally well-tolerated in a substantial proportion of participants whose SDBP remained > 90 mmHg on enalapril 10 mg. Important differences between blood pressure measured manually and with a monitor were also demonstrated. PMID- 8364946 TI - Effect of two doses of ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects. AB - The subjects of this double-blind study were 18 elderly men and women (mean age, 69.3 years) with slight age-related memory impairment. In a crossover-study design, each subject received placebo or an extract of Ginkgo biloba (EGb 761) (320 mg or 600 mg) 1 hour before performing a dual-coding test that measures the speed of information processing; the test consists of several coding series of drawings and words presented at decreasing times of 1920, 960, 480, 240, and 120 ms. The dual-coding phenomenon (a break point between coding verbal material and images) was demonstrated in all the tests. After placebo, the break point was observed at 960 ms and dual coding beginning at 1920 ms. After each dose of the ginkgo extract, the break point (at 480 ms) and dual coding (at 960 ms) were significantly shifted toward a shorter presentation time, indicating an improvement in the speed of information processing. PMID- 8364945 TI - Antihypertensive efficacy of FK906, a novel human renin inhibitor. AB - The antihypertensive efficacy of a newly developed orally active human renin inhibitor (FK906) was evaluated in 14 patients with essential hypertension aged 40 to 83 years (mean, 64 years). After a 1-week placebo run-in period, 25 mg of FK906 was given twice daily; this was increased up to 100 mg twice daily until sufficient blood pressure reduction was obtained. No adverse effects were observed in any patients. Supine blood pressure was decreased from 169 +/- 3/97 +/- 1 mmHg to 153 +/- 5/87 +/- 3 mmHg at 25 mg twice daily (n = 14), to 142 +/- 5/78 +/- 3 mmHg at 50 mg twice daily (n = 12), P < 0.01), and to 137 +/- 10/77 +/ 8 mmHg at 100 mg twice daily (n = 6, P < 0.01). The hypotensive effect was sustained over 24 hours. Pulse rate did not change. Plasma renin activity and angiotensin I were decreased after FK906 administration only in patients with increased plasma renin activity. The hypotensive effects of FK906 were not correlated with baseline plasma renin activity. Suppression of the noncirculating tissue renin-angiotensin system may account for the hypotensive action of FK906. The results suggest that FK906 is a promising antihypertensive drug in patients of all ages and with different plasma renin levels. PMID- 8364947 TI - Proarrhythmic effects of class Ic drugs. AB - Three cases managed with class Ic antiarrhythmic drugs but with subsequent aggravation of arrhythmias are reported herein. A 58-year-old man given 300 mg of flecainide for atrial flutter developed sinus arrest and transient ventricular fibrillation. A 42-year-old man with a postoperative condition of tetralogy of Fallot who received 300-mg doses of flecainide for sustained ventricular tachycardia had spontaneous sustained ventricular tachycardia. A 74-year-old man given 150 mg of propafenone for atrial tachycardia developed sustained ventricular tachycardia. The present cases illustrate that class Ic drugs may exacerbate ventricular arrhythmias, and their use may reveal concealed sinus node dysfunction. This may be due to marked slowing of conduction and prolonged ventricular refractoriness, which are characteristic of the class Ic drugs; also, it is probable that the patients' underlying cardiac conditions served as contributing factors. PMID- 8364948 TI - The influence of volatile anesthetics on portwine stain. AB - To examine the relationship between volatile inhalation anesthetics and the fading of portwine stain (PWS), the study retrospectively investigated the incidence of termination of pulsed dye laser treatment vis-a-vis PWS fade during use of a general inhalation anesthetic in 107 infants and children with facial PWS. The fading of PWS is disadvantageous to the pulsed dye laser treatment. All patients received pulsed dye laser treatment under general anesthesia using one of four kinds of volatile inhalation anesthetics (halothane, enflurane, isoflurane, and sevoflurane). Two hours before the induction of anesthesia, all patients were rectally irrigated. Treatment was discontinued in none of the 44 patients in the halothane group or the 7 patients in the enflurane group; in one of the 29 in the isoflurane group; and in 10 of the 27 patients in the sevoflurane group. The sevoflurane group showed a significantly (P < 0.01) higher incidence of PWS fading. Thus, when using a volatile inhalation anesthetic in combination with pulsed dye laser treatment for PWS, caution should be exercised if sevoflurane is selected, as PWS fading is harmful to the pulsed dye laser. PMID- 8364949 TI - Comparison of ketorolac and meperidine in patients with postoperative pain- impact on health care utilization. AB - A double-blind, randomized study was conducted to compare the effects of intramuscular ketorolac tromethamine and meperidine hydrochloride, and subsequent oral pain medication, on health care utilization and postoperative recovery. Following abdominal hysterectomy or cholecystectomy, 210 patients (aged 18 to 70 years; 189 women, 21 men) were randomly assigned to therapy and evaluated for efficacy, safety, nursing care requirements, functional independence, recovery milestones, and quality of life. The patients received 30 mg of ketorolac intramuscularly every 3 to 6 hours as needed, followed by 10 mg of ketorolac every 4 to 6 hours, or 100 mg of meperidine intramuscularly every 3 to 6 hours as needed, followed by acetaminophen/codeine (600 mg/60 mg) orally every 4 to 6 hours. Patients receiving ketorolac had lower nursing utilization scores and achieved a higher level of functioning than patients receiving meperidine during the first 3 postoperative days. Times to first bowel movement, walking without assistance, and first oral fluids were significantly shorter after ketorolac than meperidine. Mean pain intensity difference (from baseline) scores and pain relief scores when adjusted for baseline pain severity were comparable between ketorolac and meperidine. Most adverse events reported by the patients were mild to moderate; 12 patients in each group withdrew from treatment because of adverse events (nausea, rash, or headache). It is concluded that ketorolac is an effective alternative to meperidine in the management of postoperative pain. PMID- 8364950 TI - The financial impact of OBRA-90 on community pharmacies: an overview. AB - The Omnibus Budget Reconciliation Act of 1990 (OBRA-90) may be the most significant piece of legislation affecting the practice of pharmacy since the Durham-Humphrey amendments to the Food, Drug and Cosmetic Act. As part of the OBRA-90 legislation, the Health Care Financing Administration (HCFA) was required to publish estimates of the impact of the act on states, Medicaid recipients, and pharmacies. Numerous stakeholders and researchers have commented on the HCFA estimates. We have summarized the estimates available in comments and studies and conducted a sensitivity analysis on these estimates. Our results demonstrate considerable variation in the factors important in estimating the impact of OBRA 90 on pharmacy operations. This variation indicates the scarcity of empirical data needed to produce reliable impact estimates. Demonstration projects are needed to scientifically evaluate the total impact of OBRA-90 on pharmacy practice. Moreover, further investigation of the impact of the legislation on program recipients and states is warranted. PMID- 8364951 TI - Medication compliance: the patient's perspective. AB - There has been increasing interest in using outcomes-based research to evaluate quality of care. Compliance with prescribed regimens is an intermediate outcome measure that presumes that a positive health outcome will follow, which is why clinicians and researchers are interested in compliance. Patients, however, use a variety of criteria to determine the value of medication. They may place equal or greater value on personal and often competing nonclinical outcomes. A small but growing literature explores the influence of physical, economic, psychological, and social factors that influence medication use behavior. This literature supports the notion that patients evaluate medication based not only on its clinical effectiveness, but also how it affects all aspects of their lives. Outcomes research on compliance with prescribed medicine should recognize the outcomes valued from the patient's perspective. PMID- 8364952 TI - Conversion from glipizide to glyburide: long-term follow-up of a cost-impact survey focusing on the elderly. AB - The appropriate use of second-generation oral hypoglycemic agents is limited by the lack of definitive guidelines for their use in elderly diabetic patients and controversy over relative dosing equivalence. We previously conducted a survey to determine the feasibility and cost of converting diabetic patients from glipizide to glyburide. This new survey provides an extended, 24-month follow-up in 210 patients and focuses on findings in elderly patients. The mean final daily dose of glyburide (11.6 mg) was lower than the preconversion dose of glipizide (18.7 mg) (P < or = 0.0001). One hundred forty-one (67%) patients successfully continued glyburide for 24 months, including 103 (73%) patients who were 65 years of age or older. There was no apparent correlation between age and final dose of glyburide, ability to continue glyburide, or risk of stopping glyburide. The conversion program reduced the mean daily dose after switching from glipizide to glyburide, which was preserved throughout the observation period. The program also conferred a 49% savings in the projected 2-year expenditures for second generation oral hypoglycemic agents. PMID- 8364953 TI - Neuropeptides in the insect brain: a review. PMID- 8364955 TI - Identification of M cells and their distribution in rabbit intestinal Peyer's patches and appendix. AB - The distribution of intestinal membranous (M) cells has been studied within the follicle-associated epithelium of rabbit Peyer's patches and appendix. Vimentin expression has been assessed as a primary criterion to identify rabbit M cells in tissue sections and in whole tissue preparations. This criterion has been compared to the use of the absence of alkaline phosphatase which, due to its heterogeneous distribution within the enterocyte population, is less reliable than vimentin expression as a marker for rabbit M cells. The pattern of vimentin immunostaining revealed that the majority of M cells are located in the periphery of the follicle-associated epithelium, the dome apex being largely free of M cells. This distribution was confirmed by scanning electron microscopy. Vimentin is also expressed by follicle-associated epithelial cells in the vicinity of crypts which lack the typical lymphocyte-containing pocket of M cells. Cytoplasmic peanut agglutinin binding coincides with vimentin-expression throughout the follicle-associated epithelium but is absent from vimentin negative enterocytes. The co-localisation of these two phenotypic markers in both M cells and epithelial cells adjacent to crypts, which lack the typical morphology of fully developed rabbit M cells, suggests that they correspond to immature M cells which by their location appear to derive directly from undifferentiated crypt stem cells and not from mature columnar enterocytes. PMID- 8364954 TI - Endocardial endothelium in the rat: cell shape and organization of the cytoskeleton. AB - The cytoskeleton in endocardial endothelium of rat heart was examined by en face confocal scanning laser microscopy. In the ventricular cavity, endocardial endothelial cells had a polygonal shape and F-actin staining was generally restricted to the peripheral junctional actin band. Central F-actin bundles, or stress fibers, in endocardial endothelial cells were found on the tendon end of papillary muscles, especially in the right ventricle, and frequently in the outflow tract of both ventricles; elsewhere, stress fibers were scarce. Many endocardial endothelial cells were elongated in areas of endothelium with stress fibers, but no correlation was found between cell elongation and the number of stress fibers. An inverse correlation was found between the number of stress fibers and the surface area of endocardial endothelial cells. Shear stress as well as mechanical deformation of the surface of the ventricular wall during the cardiac cycle may affect cell shape and the organization of actin filaments in endocardial endothelial cells. Vimentin in endocardial endothelial cells formed a filamentous network with some distinct cytoplasmic and juxtanuclear vimentin bundles. No perinuclear ring of vimentin filaments was observed in endocardial endothelium. Microtubules in endocardial endothelial cells were, in contrast to endothelial cells of rat aorta, not aligned, less closely packed and originated from randomly distributed centriolar regions. The cytoskeleton has been suggested to play an important role in cellular functions of vascular endothelial cells. Accordingly, differences in the cytoskeletal organization between endocardial and vascular endothelial cells may relate to differences in functional properties. PMID- 8364956 TI - Immunohistochemical colocalization of 7B2 and 5HT in the neuroepithelial bodies of the lung of Rana temporaria. AB - The neuroendocrine cell population of the lung of Rana temporaria has been studied by means of immunocytochemistry. Serotonin (5HT)- and polypeptide 7B2 immunoreactive neuroepithelial bodies have been observed in the epithelial lining of the lung. 5HT- but not 7B2-immunoreactive isolated endocrine cells have also been observed. PMID- 8364957 TI - Survival and proliferation of rat gonocytes in vitro. AB - Quiescent gonocytes were isolated from fetal testes of rat 18-day post coitum and cultured alone or on monolayers of somatic cells from different origins. The gonocytes specifically adhered to Sertoli cells, isolated from 21 to 23-day-old rat testes; this adherence was necessary for their survival in vitro. Addition of follicle-stimulating hormone and testosterone to these cultures did not increase the viability of the gonocytes. Serum was found to be deleterious to the germ cells. Electron-microscopic examination of Sertoli-cell-gonocyte co-cultures revealed the presence of numerous adhesion plaques between these cells, indicating that Sertoli cells and gonocytes are able to communicate in vitro. Gonocytes, in co-culture with Sertoli cells, were viable for at least 9 days. The gonocytes did not spontaneously resume proliferation. The simple culture system described in the present paper should be useful in studying the nature of the factors that are responsible for sending the quiescent gonocytes into the cell cycle and for stimulating the formation of A spermatogonia, a process characterizing the start of spermatogenesis. PMID- 8364958 TI - Gap junctions in ovarian follicles of Drosophila melanogaster: inhibition and promotion of dye-coupling between oocyte and follicle cells. AB - The analysis of chimeras has shown that communication between germ-line and soma cells plays an important role during Drosophila oogenesis. We have therefore investigated the intercellular exchange of the fluorescent tracer molecule, Lucifer yellow, pressure-injected into the oocyte of vitellogenic follicles of Drosophila. The dye reached the nurse cells via cytoplasmic bridges and entered, via gap junctions, the somatic follicle cells covering the oocyte. The percentage of follicles showing dye-coupling between oocyte and follicle cells was found to increase with the developmental stage up to stage 11, but depended also on the status of oogenesis, i.e., the stage-spectrum, in the respective ovary. During late stage 10B and stage 11, dye-coupling was restricted to the follicle cells covering the anterior pole of the oocyte. No dye-coupling was observed from stage 12 onwards. During prolonged incubation in vitro, the dye was found to move from the follicle cells back into the oocyte; this process was suppressable with dinitrophenol. Dye-coupling was inhibited when prolonged in vitro incubation preceded the dye-injection. Moreover, dye-coupling was inhibited with acidic pH, low [K+], high intracellular [Ca2+], octanol, dinitrophenol, and NaN3, but not with retinoic acid, basic pH, or high extracellular [Ca2+]. Dye-coupling was stimulated with a juvenile hormone analogue and with 20-hydroxyecdysone. Thus, gap junctions between oocyte and follicle cells may play an important role in intercellular communication during oogenesis. We discuss the significance of our findings with regard to the electrophysiological properties of the follicles, and to the coordinated activities of the different cell types during follicle development and during the establishment of polarity in the follicle. PMID- 8364959 TI - Peripheral projections of nervus terminalis LHRH-containing neurons in the tiger salamander, Ambystoma tigrinum. AB - The peripheral projections of the nervus terminalis (NT) have been difficult to examine due to the weak immunoreactivity of the processes to various antibodies. We performed two experimental manipulations in the tiger salamander in an attempt to increase the luteinizing hormone-releasing hormone-immunoreactive (LHRH-ir) labelling in the peripheral processes of the NT:1) the NT was sectioned centrally, or 2) a 100 mg melatonin pellet was embedded subcutaneously for 3 days prior to sacrifice. Following these manipulations, animals were sacrificed and tissue was processed with standard immunocytochemical techniques for the analysis of the distribution of LHRH-ir processes. In the nasal cavity, LHRH-ir fibers were observed projecting 1) into the rostral olfactory epithelium, 2) to Bowman's glands in the lamina propria of the rostromedial olfactory mucosa and ventrolateral mucosa between the main nasal cavity and Jacobson's organ, 3) into the naris constrictor muscle, and 4) along the palatine nerves and ganglia. These lesion and hormone manipulations have enabled the detection of peripheral projections of the NT not observed previously with immunocytochemical procedures alone. The wide distribution of LHRH-ir NT processes in the nasal cavity and cranium suggests that this nerve may influence many different cranial structures during appropriate pheromonal or neuroendocrine events. PMID- 8364960 TI - The basement membranes of cryofixed or aldehyde-fixed, freeze-substituted tissues are composed of a lamina densa and do not contain a lamina lucida. AB - When tissues are processed for electron microscopy by conventional methods, such as glutaraldehyde fixation followed by rapid dehydration in acetone, basement membranes show two main layers: the electron-lucent "lamina lucida". (or rara) and the electron-dense "lamina densa". In an attempt to determine whether this subdivision is real or artefactual, two approaches have been used. Firstly, rat and mouse seminiferous tubules, mouse epididymis and associated tissues, and anterior parts of mouse eyes were subjected to cryofixation by instant freezing followed by freeze substitution in a -80 degrees C solution of osmium tetroxide in dry acetone, which was gradually warmed to room temperature over a 3-day period. The results indicate that, in areas devoid of ice crystals, basement membranes consist of a lamina densa in direct contact with the plasmalemma of the associated cells without an intervening lamina lucida. Secondly, a series of tissues from mice perfused with 3% glutaraldehyde were cryoprotected in 30% glycerol, frozen in Freon 22 and subjected to a 3-day freeze substitution in osmium tetroxide-acetone as above. Under these conditions, no lamina lucida accompanies the lamina densa in the basement membranes of the majority of tissues, including kidney, thyroid gland, smooth and skeletal muscle, ciliary body, seminiferous tubules, epididymis and capillary endothelium. Thus, even though these tissues have been fixed in glutaraldehyde, no lamina lucida appears when they are slowly dehydrated by freeze substitution. It is concluded that the occurrence of this lamina in conventionally processed tissues is not due to fixation but to the rapid dehydration. However, in this series of experiments, the basement membranes of trachea and plantar epidermis include a lamina lucida along their entire length, while those of esophagus and vas deferens may or may not include a lamina lucida. To find out if the lamina lucida appearing under these conditions is a real structure or an artefact, the trachea and epidermis were fixed in paraformaldehyde and slowly dehydrated by freeze substitution. Under these conditions, no lamina lucida was found. Since this result is the same as observed in other tissues by the previous approaches, it is proposed that the lamina lucida is an artefact in these as in the other investigated basement membranes. Thus, basement membranes are simply composed of a lamina densa that closely follows the plasmalemma of the associated cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8364961 TI - Suramin-induced mucopolysaccharidosis in rat incisor. AB - Two weeks after a single injection of suramin, the secretory and post-secretory ameloblasts of the rat incisor were filled with large lysosome-like vacuoles. At the light-microscope level, these vacuoles were positively stained with Alcian blue when MgCl2 was used at a critical electrolyte concentration varying between 0.1 and 0.3 M, whereas no staining appeared when MgCl2 varied between 0.7 and 0.9 M. Hyaluronidase digestion markedly reduced but did not totally abolish the staining, indicating that glycosaminoglycans were accumulated inside these vacuoles. Examination of these cells with the electron microscope revealed a polymorphic population of large vesicles, filled to various degrees with cetylpyridinium chloride (CPC)-positive and malachite green aldehyde (MGA) positive material. The same pattern was observed in secretory odontoblasts but to a lesser extent. In the extracellular matrix, suramin-induced alterations appeared as large defects occurring during enamel formation. In predentin and dentin, the number and/or size of electron-dense aggregates resulting from CPC and MGA fixation, were enhanced in the suramin-injected rats. These aggregates were largely reduced or suppressed respectively by hyaluronidase digestion and chloroform/methanol treatment of the sections. The accumulation of glycosaminoglycans and phospholipids reported here inside ameloblasts and odontoblasts and in predentin and dentin supports the occurrence of suramin induced mucopolysaccharidosis and lipidosis in this experimental animal model. PMID- 8364963 TI - Insulin-like molecules in the beetle Tenebrio molitor. AB - Immunocytochemical staining of the nervous system of larva, pupa, and adult stage of Tenebrio molitor with anti-insulin serum demonstrated insulin-like peptides in the protocerebrum, corpora allata, and suboesophageal ganglion. During pupal development, marked changes in staining intensity of the protocerebral cells were detected. The staining pattern suggests release of insulin-like peptides early on day 0 and again on day 3 of the stadium. Injections of anti-insulin at these times caused significant delays in the timing of pupal/adult ecdysis. An immunoblot of haemolymph from day-3 pupae revealed a 6.5-kDa insulin-like molecule. These results suggest that the prothoracicotropic hormone of T. molitor is an insulin-like molecule. PMID- 8364962 TI - Architectural arrangement of stages of the spermatogenic cycle within human seminiferous tubules is related to efficiency of spermatogenesis. AB - Stages of the spermatogenic cycle in human seminiferous tubules were evaluated in men with varied efficiencies of spermatogenesis to determine if the architectural arrangement of stages or the atypical cell types contributed to variation in sperm production rates. Testes were selected from men with low, intermediate, and high daily sperm production per g parenchyma (DSP/g). Round tubular cross sections were photographed by bright-field microscopy. Stages were identified for each cross section by two observers and the number of stages represented in each cross section was recorded. Number of stages per cross section in men with low efficiency of spermatogenesis were significantly (P < 0.05) fewer than men with intermediate and high efficiency of spermatogenesis. Further, the percentage of stages with atypical cell types in men with high DSP/g was significantly (P < 0.05) higher than men with low DSP/g. There was a significant relationship (P < 0.01) between the percentages of stages with atypical cell types per stage and number of stages per cross section. The atypical cell types appear to result from high density of stages per cross section in men with high DSP/g. There was no significant difference observed between groups for tubular volume, diameter, length, volume density, and volume density of seminiferous epithelium. However, a significant (P < 0.05) positive correlation between percent seminiferous epithelium per testis with DSP/g or with the number of stages per cross section was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364964 TI - Subcellular localization of immunoreactive oxytocin within thymic epithelial cells of the male mouse. AB - Immunoreactive oxytocin is expressed by thymic epithelial cells, which share properties with neuroendocrine cells. In order to investigate the assumed paracrine secretion of oxytocin, we studied the subcellular localization of immunoreactive oxytocin within thymic tissue and cultured thymic epithelial cells of the male mouse. Three types of immunoreactive cells were distinguished with the electron microscope. Immunoreactive oxytocin was found to be restricted to the cytoplasm by the use of pre- and postembedding methods. Some epithelial cells, especially in the cortex, showed a pronounced labelling of vesicular membranes and membrane tubules of the endoplasmic reticulum. In some cells, keratin filaments were associated with the electron-dense stain. Under culture conditions immunoreactive cells of different shapes were found, all displaying similar patterns of labelling. The contents of different types of vacuoles were only rarely labelled. A special class of immunoreactive exocytotic vesicles could not be identified. Thus, our results do not support neuroendocrine secretion of oxytocin via vesicles of thymic epithelial cells but offer alternative modes of secretion. PMID- 8364965 TI - The effects of gonadectomy and testosterone treatment on the Harderian gland of the green frog, Rana esculenta. AB - The effects of gonadectomy and testosterone treatment on the fine structure of the Harderian gland in male and female green frogs were investigated in different periods of the year. Gonadectomy, carried out when the glands are in the lowest secretory phase (September), causes degenerative changes consisting of a reduction of the rough endoplasmic reticulum, the appearance of autolysosomes, and an increase of nuclear heterochromatin. These effects can be prevented by testosterone treatment. No castration effects are found during the recovery (November) and enhancement (April-May) phases of secretory activity. The results suggest that the frog Harderian gland's sensitivity to testosterone changes during the annual cycle. The androgen dependence of the Harderian gland is correlated with the presence of androgen receptors in both male and female frogs. PMID- 8364966 TI - Cellular components of the immune barrier in the spinal meninges and dorsal root ganglia of the normal rat: immunohistochemical (MHC class II) and electron microscopic observations. AB - This report deals with the distribution, morphology and specific topical relationships of bone-marrow-derived cells (free cells) in the spinal meninges and dorsal root ganglia of the normal rat. The morphology of these cells has been studied by transmission and scanning electron microscopy. Cells expressing the major histocompatibility complex (MHC) class II gene product have been recognized by immunofluorescence. At the level of the transmission electron microscope, free cells are found in all layers of the meninges. Many of them display characteristic ultrastructural features of macrophages, whereas others show a highly vacuolated cytoplasm and are endowed with many processes. These elements lack a conspicuous lysosomal system and might represent dendritic cells. Scanning electron microscopy has revealed that free cells contact the cerebrospinal fluid via abundant cytoplasmic processes that cross the cell layers of the pia mater and of the arachnoid. Cells expressing the MHC class II antigen are also found in all layers of the meninges. They are particularly abundant in the layers immediately adjacent to the subarachnoid space, in the neighbourhood of dural vessels, along the spinal roots and in the dural funnels. In addition to the meninges, strong immunoreactivity for MHC class II antigen is observed in the dorsal root ganglia. The ultrastructural and immunohistochemical findings of this study suggest the existence of a well-developed system of immunological surveillance of the subarachnoid space and of the dorsal root ganglia. PMID- 8364967 TI - The suprachiasmatic nucleus of the mink (Mustela vison): apparent absence of vasopressin-immunoreactive neurons. AB - The hypothalamic suprachiasmatic nucleus is centrally involved in generation of several circadian rhythms. Neurons of the mammalian suprachiasmatic nucleus express a number of neuropeptides including vasopressin. The suprachiasmatic nucleus of the mink (Mustela vison) is easily distinguished from neighbouring hypothalamic areas and the underlying optic chiasm as a small nucleus containing densely packed parvocellular neurons. A dorsal and ventral subdivision were clearly recognized within the midportion and caudal part of the nucleus. Using immunohistochemistry, we have identified vasopressin-, neurophysin-, and vasoactive intestinal peptide-immunoreactive neuronal elements in the hypothalamus of the mink. Vasoactive intestinal peptide-immunoreactive neurons can be observed in the ventral aspect of the suprachiasmatic nucleus, but to our surprise, no vasopressin immunoreactive perikarya are found within the suprachiasmatic nucleus, this absence being independent of the experienced annual cycle. The hypothalamic paraventricular and supraoptic nuclei contain large numbers of vasopressin-, neurophysin- and vasoactive intestinal peptide immunoreactive magnocellular neurons with extensive projections towards the infundibulum and neurohypophysis. A comparative analysis of the distribution of vasopressin-immunoreactive elements in a number of conventional laboratory animals has demonstrated that, in contrast to the rat, golden hamster and Mongolian gerbil, neither vasopressin-containing perikarya in the suprachiasmatic nucleus nor fine calibered immunoreactive fibres entering the adjacent subparaventricular zone are present in the mink. The mink is a photodependent seasonal breeder, and thus vasopressin-immunoreactive neurons in the suprachiasmatic nuclei may not be essential for the photoperiodic regulation of reproduction and seasonal events experienced by this species. PMID- 8364968 TI - Localization of inhibin/activin subunits in the testis of adult nonhuman primates and men. AB - The localization and distribution of inhibin/activin subunits was evaluated in the testes of three nonhuman primate species (Macaca fascicularis, M. mulatta, M. arctoides), of young (31 to 43 years) and old (60 to 85 years) men, and of men with disturbed or arrested spermatogenesis using immunohistochemical techniques (peroxidase-anti-peroxidase and alkaline-phosphatase/anti-alkaline-phosphatase technique). Specific polyclonal (anti-porcine inhibin alpha-1-32 and anti-bovine activin A) and monoclonal (anti-human inhibin alpha-1-32 and anti-human activin beta A-82-114) antisera were employed. Among all nonhuman primate species and in men, inhibin/activin subunits were present in the cytoplasm of Sertoli cells and Leydig cells but not in germ cells. No relationship could be established between the staining pattern for inhibin/activin subunits and the completeness or the stage of the spermatogenic process. The staining for the beta A-subunit in Sertoli cells appeared more intense in the testes of old men compared with that of young men. The majority of Leydig cells contained either the alpha-subunit and beta A-subunit or the beta A-subunit alone. The signal for the beta A-subunit was remarkably intense in normal and hyperplastic human Leydig cells. These observations demonstrate the presence of inhibin/activin subunits in Sertoli cells and Leydig cells of adult primates and raise the possibility that these subunits or their respective dimers (inhibin A/activin A) might subserve a paracrine/autocrine role in the adult primate testis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364969 TI - Evidence for a direct effect of growth hormone on osteoblasts. AB - In order to determine whether growth hormone (GH) exerts a direct effect on osteoblasts, in vitro and in vivo immunocytological studies were carried out on newborn rat calvaria and a clonal osteoblast-like cell line (MC3T3-E1) isolated from newborn mouse calvaria. After exposure to human growth hormone (hGH) or 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), a significant increase in alkaline phosphatase activity was observed in MC3T3-E1 cells. Simultaneous exposure of MC3T3-E1 cells to hGH and 10 nM 1,25(OH)2D3 showed a synergistic effect of the two hormones on this activity. The optimal dose of hGH was 0.1 nM. An immunocytological procedure was performed on ultrathin frozen sections from 7-day-old rat calvaria and MC3T3 E1 cells cultured with hGH. GH-like immunoreactivity was observed in both cases. In calvaria, endogenous GH-like immunoreactivity was localized at the same ultrastructural level (plasma membrane, cytoplasmic and nuclear matrices) as exogenous GH-like immunoreactivity in MC3T3-E1 cells. Following the initial step of binding to the plasma membrane, GH may be internalized in the cytoplasmic matrix and nucleus. In situ hybridization revealed the presence of mRNA coding for GH receptor in calvaria cells. The density of these receptors seemed to be lower in osteoblasts than in hepatocytes. In MC3T3-E1 cells, hGH induced a dose dependent secretion of insulin-like growth factor 1. In conclusion, these results indicate that GH may act directly on osteoblasts. PMID- 8364970 TI - Photoperiod-dependent changes in exocytotic activity in the hypophyseal pars tuberalis of the Djungarian hamster, Phodopus sungorus. AB - The pars tuberalis of the hypophysis of the Djungarian hamster, Phodopus sungorus, was investigated with regard to secretory activity by applying the tannic acid-Ringer perfusion technique. Two groups were maintained under long photoperiods (16 h light: 8 h dark) or short photoperiods (8 h light: 16 h dark), respectively. Perfusion with tannic acid showed that specific pars tuberalis cells release some of their secretory granules as indicated by typical exocytotic figures. The percentage of cells displaying exocytotic activity was significantly higher in the pars tuberalis of hamsters kept under long photoperiods. The number of exocytotic figures per single cell was not increased. These results provide further evidence for a secretory activity of the pars tuberalis and support the hypothesis of its involvement as a mediator between photoperiodic stimuli and the endocrine system. PMID- 8364971 TI - Distribution of intracardiac neurones and nerve terminals that contain a marker for nitric oxide, NADPH-diaphorase, in the guinea-pig heart. AB - There is strong evidence that NADPH-diaphorase can be used as a marker for neurones that employ nitric oxide as a messenger molecule. In the present study, the NADPH-diaphorase activity of intracardiac neurones and nerve terminals in whole-mount stretch preparations and sections of the newborn and adult guinea-pig atria and interatrial septum has been examined histochemically. Together with epicardial, endothelial and endocardial cells, which displayed some NADPH diaphorase staining, a subpopulation of intracardiac neurones exhibited moderate heavy labelling for NADPH-diaphorase, while the majority of neurones were only lightly stained or negative. Intracardiac ganglia containing positive neuronal cell bodies were located between the epicardial cells and atrial myocytes in four main regions: in association with the superior and inferior vena cavae, the points of entry of the pulmonary veins, and within the interatrial septum. Nerve terminals exhibiting NADPH-diaphorase activity were seen throughout the atrial tissue, forming basket-like endings around intracardiac neuronal cell bodies; varicose terminals were also observed on atrial myocytes and other non-neuronal structures. A proportion of the nerve fibres was clearly of intrinsic origin, other terminals may well have originated from neuronal cell bodies present outside the heart. PMID- 8364972 TI - Stimulation-induced damage in rabbit fast-twitch skeletal muscles: a quantitative morphological study of the influence of pattern and frequency. AB - The aim of this study was to determine whether muscle fibre degeneration brought about by chronic low-frequency electrical stimulation was related to the pattern and frequency of stimulation. Rabbit fast-twitch muscles, tibialis anterior and extensor digitorum longus, were stimulated for 9 days with pulse trains ranging in frequency from 1.25 Hz to 10 Hz. Histological data from these muscles were analysed with multivariate statistical techniques. At the lower stimulation frequencies there was a significantly lower incidence of degenerating muscle fibres. Fibres that reacted positively with an antineonatal antibody were most numerous in the sections that revealed the most degeneration. The dependence on frequency was generally similar for the two muscles, but the extensor digitorum longus muscles showed more degeneration than the tibialis anterior at every frequency. Muscles subjected to 10 Hz intermittent stimulation showed significantly less degeneration than muscles stimulated with 5 Hz continuously, although the aggregate number of impulses delivered was the same. The incidence of degeneration in the extensor digitorum longus muscles stimulated at 1.25 Hz was indistinguishable from that in control, unstimulated muscles; for the tibialis anterior muscles, this was also true for stimulation at 2.5 Hz. We conclude that damage is not an inevitable consequence of electrical stimulation. The influence of pattern and frequency on damage should be taken into account when devising neuromuscular stimulation regimes for clinical use. PMID- 8364973 TI - A monoclonal antibody disrupting cell-cell adhesion of rat ascites hepatoma cells. AB - A cell surface-associated adhesive factor (AF) separated from differentiated rat ascites hepatoma AH136B cells (forming cell islands in vivo) has been highly purified by chromatography. AF is assumed to mediate the cell-cell adhesion essential to island formation of the hepatoma cells. A substance, immunologically cross-reactive with AF, is present in the ascites fluid or culture medium of the AH136B cells. Because the substance is almost identical to AF in molecular weight and aggregation-promoting activity, it has been concluded that AF is released into the ascites fluid where it is concentrated. Monoclonal antibodies have been raised against AF purified from ascites fluid of AH136B cells. We have obtained a monoclonal antibody, coded MoAF-6D6, that strongly abolishes the aggregation promoting activity of AF. When AH136B cell islands are incubated in the presence of Fab fragments of MoAF-6D6, cell detachment from the islands is evident within 24 h. Cell islands following 36-h culture show a distinct dissociation and islands completely lose their organization 48 h after culture. The dissociating effect of MoAF-6D6 is neutralized by the addition of AF. These results suggest that AF plays a significant role in the maintenance of cell islands. PMID- 8364974 TI - Neurons in a variety of molluscs react to antibodies raised against the VD1/RPD2 alpha-neuropeptide of the pond snail Lymnaea stagnalis. AB - The VD1 and RPD2 neurons of Lymnaea stagnalis innervate other central neurons, certain skin areas, the pneumostome area, and the auricle of the heart. Recently, a set of four (delta, epsilon, alpha, beta) neuropeptides produced by these giant neurons and by certain other central neurons has been characterized. Although alternative splicing of the preprohormone of these neurons yields at least 10 different alpha neuropeptides, an affinity-purified antiserum directed against a domain common to all alpha neuropeptides has previously been shown to be highly selective in staining VD1, RPD2 and other neurons that produce the preprohormone. Since the gene encoding the neuropeptides is structurally similar to that expressed in R15 of the marine opisthobranch Aplysia californica, we have used the affinity purified antiserum as a marker for VD1/RPD2-related systems in other molluscs. Immunopositive neurons and fibers are observed in the central nervous systems of all species studied (Achatina fulica, Anodonta sp., Aplysia brasiliana, A. californica, Bulinus truncatus, Cepea sp., Eobania vermiculata, Helix aspersa, H. pomatia, Limax maximus, Mytilus edulis, Nassarius reticulatus, Viviparus viviparus). Several medium-sized and small neurons and 1-4 giant neurons are found in the pulmonates and opisthobranchs. The giant neurons in pulmonates have locations in the subesophageal ganglion, axonal branching patterns, and terminal arborizations in the auricle of the heart; all these characteristics are similar to those of VD1 and RPD2. Double-labelling (Lucifer yellow injection, immunocytochemistry) confirms that the two giant neurons in Helix pomatia are Br and Br'. The immunoreactive cells in A. fulica appear to include the VIN and PON neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364975 TI - Expression of vigilin in chicken cartilage and bone. AB - The expression of vigilin was followed during chick embryonal development by in situ hybridization. Vigilin mRNA is abundantly expressed in tissues of mesenchymal and ectomesenchymal origin. The mesenchymal primordial cells of cartilage and bone did not show any significant expression of vigilin. As tissue differentiation proceeded, vigilin mRNA levels increased in hyaline cartilage and in both endochondral as well as intramembranous bone. The results suggest that the expression of vigilin mRNA in cartilage- and bone-forming cells, chondrocytes and osteoblasts, is dependent on the stage of development and cellular differentiation, although not a unique process of bone formation. Most striking is the correlation of the maximum vigilin mRNA expression in osteoblasts and hypertrophic chondrocytes to periods when cell-specific genes were highly transcribed and substantially translated, e.g., synthesis of procollagen and formation of extracellular matrix in bone and cartilage. PMID- 8364976 TI - Principles of biotechnological treatment of industrial wastes. AB - This review includes current information on biodegradation processes of pollutants, digestor biocenosis and bioadditives, sludge production, measurement of pollution, and advances regarding biotechnological treatment of a series of specific industrial effluents. PMID- 8364977 TI - Neurotensin-amplification of DNA synthesis stimulated by EGF or TGF alpha in primary cultures of adult rat hepatocytes. AB - Epidermal growth factor and transforming growth factor alpha stimulated DNA synthesis in primary cultures of adult rat hepatocytes. In the presence of neurotensin, the stimulatory effect of epidermal growth factor or transforming growth factor alpha on DNA synthesis was enhanced 3- to 5-fold. Since neurotensin by itself did not stimulate DNA synthesis at all concentrations tested, enhancement of DNA synthesis by neurotensin is due to the amplification of the effect of epidermal growth factor or transforming growth factor alpha. The amplification by neurotensin was observed in a dose-dependent manner with a maximal effect at 10(-8)M, although its effect was significantly observed at as low as 10(-10) M. This neurotensin amplification of DNA synthesis was observed when hepatocytes were cultured in Williams' medium E, but not in Leibovitz L-15 medium, suggesting that minor components in the medium are required for hepatocytes to fully respond to neurotensin. Neurotensin-related peptides such as kinetensin or neuromedin-N did not have this amplifying effect on DNA synthesis at any concentration tested. From these results, neurotensin can be regarded as a new secondary mitogen. PMID- 8364978 TI - Information propagation by spatio-temporal pattern change of Ca2+ concentration throughout Physarum polycephalum with repulsive stimulation. AB - The development of a spatio-temporal pattern of Ca2+ concentration (Ca2+ pattern) in the plasmodium of Physarum polycephalum during repulsive response was studied using fura-2. In the migrating cell, the gradient of the Ca2+ concentration (Ca2+ gradient) immediately showed a decrease in local concentration in the area (S site) stimulated by 50 mM KCl. The concentration rose and then decreased in a site neighboring the S-site. This transient increase of Ca2+ concentration, the duration of which was approx. 10 minutes, was propagated to the site most distant from the S-site. There, the Ca2+ concentration gradually rose and remained at a high level. Twenty-five minutes after stimulation, a new Ca2+ gradient was established throughout the plasmodium. The migratory direction of the cell as a whole then changed. In this process, although the period of Ca2+ oscillation changed at the S-site, this change was only local to the site. During the information processing of the local repulsive stimulus, the transient Ca2+ increase propagated the local information about the stimulus to the non stimulation sites (NS-sites), leading to the generation of a new pattern and the start of coordinated migration of the plasmodium. PMID- 8364979 TI - Effect of hepatocyte growth factor on cadherin-mediated cell-cell adhesion. AB - Hepatocyte growth factor (HGF) is known to induce the dispersion of epithelial cells, as scatter factor. On the other hand, cadherins play a crucial role in connecting cells together. Two groups of cadherins are involved in epithelial cell adhesion, those locating in adherens junctions (AJ) and in desmosomes. Here, we examined the effect of HGF on the function of these cadherins in keratinocyte cell lines F and 308R, which expressed E- and P-cadherin in AJ (referred to as AJ cadherins) and desmoplakin in desmosomes. In the presence of HGF, these cells spread more extensively than in control cultures and their associations apparently loosened. However, they maintained cell-cell contacts where cadherins and desmoplakin concentrated, although the level of the concentration was reduced by HGF treatment. When antibodies to E- and P-cadherins were added to cultures of these cells without HGF, AJ cadherins were redistributed into non-junctional areas of the cells, but desmoplakin still localized at cell-cell boundaries. When HGF was added together with anti-AJ cadherin antibodies to the cultures, cell cell contacts were now disrupted. In these cultures, not only AJ cadherins but also desmoplakin were lost at cell-cell contact sites, indicating that HGF can disrupt desmosomal cell-cell adhesion when AJ cadherins are inactive. These results suggest that, although HGF cannot block cadherin-mediated cell-cell adhesion when the entire cadherin system is intact, it might modulate the activities of cadherins, especially, of desmosomal cadherins. PMID- 8364980 TI - The effect of cytokines on the differentiation of an eosinophilic leukemia cell line (EoL-1) is associated with down regulation of c-myc gene expression. AB - In this study, we measured hydrogen peroxide (H2O2) release as one of the functions of mature eosinophils, and utilized it as a quantitative index. We demonstrated that 1) the human eosinophilic leukemia cell line, EoL-1, did not release H2O2 when stimulated with phorbol myristate acetate (PMA), but after culturing with tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) it acquired the ability to release H2O2; 2) the ability to release H2O2 was time dependent and reached a peak after 4 days of culture; 3) administration of TGF beta or GM-CSF, with TNF and IFN-gamma enhanced the PMA-induced release of H2O2 from EoL-1. To examine the potential relationship between c-myc gene expression and induction of the ability to release H2O2, Northern analysis of c-myc gene expression in EoL-1 cocultured with TNF and IFN-gamma was performed. The results showed that the c-myc gene was spontaneously expressed in EoL-1, and the level of c-myc mRNA was markedly reduced after the cells were cocultured with TNF and IFN gamma, suggesting that the decrease of the c-myc mRNA level is closely associated with induction of the ability to release H2O2. PMID- 8364981 TI - Characterization of a hepatocyte growth factor derived from nonparenchymal liver cells. AB - A growth factor stimulating DNA synthesis of adult rat hepatocytes in primary culture was found in the conditioned medium after culturing nonparenchymal liver cells (NPC). Adding heparin to the NPC cultured medium stimulated the growth factor secretion from NPC. The growth factor was secreted mainly by Kupffer cells. The partially purified growth factor from the NPC appeared to be related to the HGF isolated from platelets according to three criteria: (a) binding to Heparin-Sepharose and eluting at about 0.65 M NaCl, (b) having a Mr of about 70 kDa, (c) having an immunoreactivity to antibody against rat platelet-derived HGF. Adding heparin to the NPC cultured medium also resulted in protection of the growth factor from heat- and acid-inactivation, but the direct interaction of heparin with the partially purified growth factor did not lead to such protection. Perfusion of normal adult rat livers with Hanks' solution containing 1 M NaCl in situ led to the release of large amounts of hepatocyte growth factor (10). These findings suggest that the hepatocyte growth factor derived from NPC binds to ECM between the layer of hepatocytes and endothelial cells forming the sinusoids in normal adult rat liver and that this may play a role in stabilization and maintaining the pool of HGF, which functions to constantly supply HGF in the setting of liver regeneration. PMID- 8364983 TI - Biochemistry of the intervertebral disc. AB - In comparison to other tissues, understanding the disc biochemistry is only in the very early stage. The few facts that are known would point to strategies for interventions to alter disc biology and maintain disc biomechanics. PMID- 8364982 TI - Close correlation between cytoplasmic Ca++ levels and release of an endothelium derived relaxing factor from cultured endothelial cells. AB - We studied whether there is a quantitative relationship between free cytosolic Ca++ levels and the release of an endothelium-derived relaxing factor (EDRF) from cultured fetal bovine aortic endothelial cells (EC). EC pretreated with indomethacin were stimulated by the agonists adenosine triphosphate (ATP), bradykinin (BKN), acetylcholine (ACh) and calcium ionophore (A23187) in various concentrations (10(-8)-10(-5) M), and the amount of EDRF released was determined on the basis of endothelium-free rabbit aortic ring relaxation and cultured smooth muscle cell cGMP content. Changes in intracellular Ca++ concentration ([Ca++]i) in response to the same stimuli were determined by photometric fluorescence microscopy using the fluorescent calcium indicator Fura-2. EC stimulation by ATP and A23187 induced dose-dependent increases in both [Ca++]i and the amount of EDRF released. BKN increased both [Ca++]i and EDRF release upon initial exposure (10(-8)M), but there were no further changes at higher concentrations. ACh induced no significant changes in either [Ca++]i or EDRF release. There was a close quantitative correlation between agonist-induced changes in [Ca++]i and the amount of EDRF released (relaxation response in aortic rings and cGMP levels.) (p < 0.001) Removal of extracellular Ca++ eliminated continuous elevation in both [Ca++]i and the amount of EDRF induced by ATP (10( 5)M), BKN (10(-8)M) and A23187 (10(-6)M). These findings suggest that intracellular Ca++ levels are directly linked to the amount of EDRF released, and that extracellular Ca++ is essential for EDRF release because its influx is involved in the continuous elevation of [Ca++]i. PMID- 8364984 TI - Spinal injury in sport: epidemiologic considerations. AB - Review of previous epidemiologic studies, involving both contact and noncontact sports at all levels of competition ranging from the high school level to the professional level, reveals that the overwhelming majority of sports injuries related to the spine are soft-tissue injuries and self-limiting. The spectrum of injury is related to the mechanism, the force involved, and the point of application of the force. The immediate consequence of a soft-tissue injury is decreased immobilization with result in deconditioning. Most athletes have a strong desire to compete both at the amateur and professional levels. The inability to compete can have both psychologic and emotional consequences. The professional athlete is potentially burdened with financial consequences as well. The mainstay of prevention and treatment is maintaining good strength and flexibility through conditioning. Injuries can occur at the level of the disc, resulting in disc herniation, disc degeneration, and ultimately developmental stenosis. The biochemistry and biomechanics of the disc are age related, and thus, the adolescent and older athlete may have different concerns with regards to the diagnosis, treatment, and prognosis after injury to the spine. Remember, not only injuries cause back pain in the athlete. Athletes, too, can have tumors, infection, rheumatologic disorders, and other nontraumatic etiologies of back pain. Rarely athletic injuries to the spine do result in significant neurologic compromise. These injuries have been brought to national attention with the tragic recent injuries of well-known professional football and hockey athletes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8364985 TI - Biomechanics of the spine in sports. AB - An understanding of spinal mechanics is necessary for the treatment of athletic injuries. Recognizing and isolating the mechanism of injury through noninvasive techniques will lead to specific treatment for that injury. Because the prevention of physical injury is the goal of all health care professionals, the authors hope that the information will be helpful. PMID- 8364986 TI - The lumbar spine in the aging athlete. AB - The relative importance of an elderly individual's chosen athletic endeavor should not be underestimated. These athletes have high expectations of their physical abilities. A lumbar spine syndrome can be a severe physical and psychologic setback. The ideal goal in the treatment of this population is to make an accurate diagnosis and provide expeditious treatment that allows the athlete to return to a satisfactory level of competition. The described algorithm is useful in attaining this goal. In addition, patient education is particularly important in preventing reinjury. PMID- 8364987 TI - Diagnostic imaging of sports-related spinal disorders. AB - Diagnostic imaging is a dynamic field that has taken a quantum leap over the past several years with the advent of MRI. Accordingly, it is integral that the sports medicine clinician be well acquainted with the sundry imaging modalities at his or her disposal, and be able to choose the appropriate study or studies that will provide the most useful and accurate information. Conventional radiography should be the first study performed in every athlete with sports-related injury to the spine. If radiography reveals evidence of spondylolysis with or without spondylolisthesis, MRI would be an extremely helpful adjunct for evaluation of the disc spaces, nerve roots, and neural foramina. Osseous fragments in the vicinity of the pars defect are well seen on CT but not MRI. These fragments can migrate and become symptomatic. Therefore, in the work-up of this subset of patients, CT does offer important supplementary data to the MRI. When conventional radiographs of the cervical spine corrected for magnification render the diagnosis of congenital cervical spinal stenosis, MRI should invariably be the next procedure of choice for evaluation of the spinal cord and to assess the functional reserve of the spinal canal. MRI is also the modality of choice now for evaluation of the athlete with degenerative disc disease and for the identification of degenerative disc disease associated with lumbar Scheuermann's disease. In the athlete with an acute cervical spine injury, following conventional radiography, the patient should be evaluated with CT to better characterize and define the extent of the fracture and to search for additional fractures. MRI should be performed in these patients after CT as it provides extremely valuable information regarding the status of the spinal cord. MRI because of its unparalleled soft-tissue contrast, noninvasive nature, ability to image in three orthogonal planes, and myelographic effect with certain pulses sequences has become the ideal imaging modality for spinal disease, and sports related spinal disorders are certainly no exception. PMID- 8364988 TI - Spine instability and the special olympics. AB - There is a broad array of abnormalities of the upper cervical spine in people with Down syndrome, with an increased atlanto-dens interval being the best known. Most patients are asymptomatic. The natural history, however, is not known, and therefore, treatment recommendations are based on important clinical determinants. PMID- 8364989 TI - Spondylolysis and spondylolisthesis in the athlete. AB - Spondylolysis and spondylolisthesis are common causes of back and leg pain in the athletic population. Spondylolysis originates most often in children between 5 and 10 years of age. Many types of athletic activities requiring lumbar extension and rotation place the immature spine at risk for developing these lesions. PMID- 8364990 TI - Isokinetic back testing in the athlete. AB - With increasing numbers of professional, collegiate, and high school athletes developing low back pain, isokinetic back testing could prove to be a way of preventing the development of severe problems and extended stays on injured lists. Isokinetic testing provides an advantage over other testing procedures by more closely simulating the way muscles perform functional activities. This type of testing allows comparison between patients, normals, preoperative and postoperative status, and pre-rehabilitation and post-rehabilitation protocols. PMID- 8364991 TI - Nonoperative treatment of low back injury in athletes. PMID- 8364992 TI - Percutaneous lumbar discectomy. AB - The role of percutaneous lumbar discectomy as an adjunct in the treatment of herniated lumbar discs has become increasingly recognized. This article discusses its history, indications, techniques, and results. PMID- 8364993 TI - Laser discectomy. AB - Discectomy with lasers is a technically easy procedure and permits a surgeon to place a predictably sized and configured defect in a predetermined position in the intervertebral disc. In a small series of patients, the procedure appears effective in controlling symptoms in a high percentage of patients. The efficacy of the procedure and wider acceptance will depend on the results of multicenter clinical trials. PMID- 8364995 TI - Arthroscopic microdiscectomy versus nucleotomy techniques. AB - Arthroscopic microdiscectomy represents an alternative method of treatment for herniated lumbar disc and its associated radiculopathy. In contrast to nucleotomy procedures that allow for only central evacuation of the nuclear mass, in arthroscopic microdiscectomy, the emphasis is placed on evacuation of the posterior collagenized fragments, which are responsible for mechanical compression of the nerve roots. Over a period of 10 years, 250 patients with unremitting sciatica due to herniated nucleus pulposus have been treated at the Graduate Hospital through a posterolateral approach via a 6.5-mm cannula. Our overall successful results have been 87.5%, and we have not encountered any neurovascular or other serious complications. PMID- 8364994 TI - Surgical disc excision. AB - For the athlete, whether recreational or professional, limited surgical discectomy has been a predictable and highly successful procedure, enabling those individuals to return to their preinjury status relatively quickly. With proper patient selection, patients will be able to return to their athletic endeavors with much more reliability than with any of the other currently available surgical alternatives to limited surgical discectomy. PMID- 8364997 TI - Rehabilitation of athletes following spine injury. AB - We feel that the described system for staging cervical and lumbar spine injuries in the high-performance athlete affords a basic framework for the rehabilitation of those individuals. With spine injuries, one has to exercise care to rule out those injuries and additional pathologies presenting as neck or back pain that could result in catastrophic sequelae. We stress due diligence in the initial and continued follow-up of these patients with careful evaluation to rule out associated fractures, dislocations, and attendant disc pathology. The treatment of the "stinger" or "burner" is controversial. We suggest a conservative approach, although the orthopedic and neurologic literature reports that these individuals have been returned to full contact sports activity without documented subsequent neurologic sequelae. The final decision remains at the discretion of the treating physician. This program provides a rational approach to the rehabilitation of the spine-injured high-performance athlete that will provide for the return of him or her to preinjury activity level in an expeditious manner with the minimal period of interruption in training. PMID- 8364996 TI - Spinal fusion in the athlete. AB - Although there are a few anecdotal descriptions of the athlete who has gone on to win fame and fortune following a successful spinal fusion, there has been little, if any, scientific data available to aid the surgeon in his treatment of these highly motivated patients. At present, there is no guide to patient selection or to the operative procedure of choice. There is no standard postoperative rehabilitation program, and to date, an outcome study is sadly lacking. Therefore, it is worthwhile to look into this subject in greater detail. PMID- 8364998 TI - Intracanalicular acoustic neuromas: a conservative approach. PMID- 8364999 TI - Remodelling of the normal incus. AB - Thirty normal incudes were examined using scanning electron microscopy (SEM) to assess the pattern and degree of bony remodelling. The body and short process appeared stable throughout life. By contrast, the lenticular and long processes demonstrated marked osteoclastic activity with a tendency to undergo progressive erosion with advancing age. PMID- 8365000 TI - The effect of histamine challenge on nasal airflow sensation. AB - Objective nasal airflow resistance, as measured by the rhinomanometer, and the subjective sensation of nasal patency are usually regarded as showing poor correlation. However, previous population studies comparing nasal resistance and subjective nasal airflow sensation have failed to take into account the great individual variation in resting nasal resistance. To investigate the potential relationship between the two parameters, 20 healthy volunteers underwent histamine nasal challenge tests. Nasal resistance prior to the intra-nasal administration of histamine ('resting' nasal resistance, NRR) was compared with nasal resistance when the subject reported a subjective sensation of nasal blockage ('obstructed' nasal resistance, NR0) and the two were found to be significantly correlated using the Spearman rank correlation method (rs = 0.648, P = 0.002). Linear regression analysis using the method of least squares demonstrated an association between the two variables (P = 0.029), conforming to the formula NR0 = 1.26NR+0.478, (resistance units kPa.s.l-1). Subjective and objective measurements of nasal patency may be much more closely related than has previously been reported. PMID- 8365001 TI - A model to refine the selection of children with otitis media with effusion for adenoidectomy. AB - The selection of children with otitis media with effusion for adenoidectomy has been criticized on a number of grounds. In spite of the widespread popularity of the procedure there are few objective guidelines to help the otolaryngologist make a decision which is therefore usually subjective. We present a scientifically derived model using a Generalized Linear Interactive Modelling (GLIM) technique from a population of 122 children who underwent either adenoidectomy or no pharyngeal surgery. The outcome parameter studied was otoscopic clearance in an unoperated ear 1 year after treatment. This was related principally to the operation type (P < 0.001) and to the age at which the operation was performed (P < 0.005). Using a probability of clearance threshold of 50% the model was tested on a prospective population of 166 children and outcome was correctly predicted in over 72%. This model enables the surgeon to determine the probability of clearance of effusion following adenoidectomy in an individual child. At a probability threshold of 50% adenoidectomy would be offered to children with bilateral otitis media with effusion aged between 4.33 and 8.00 years. Over the age of 8 years the probability of clearance occurring spontaneously increases beyond 50%. By careful selection of the probability of clearance thresholds it was possible to produce otoscopic resolution in over 80% of those selected to undergo adenoidectomy. The model also enables the otolaryngologist to determine the proportion of children with established disease that require adenoidectomy at his own chosen probability thresholds which will ensure that a more effective resource allocation is achieved. PMID- 8365002 TI - A morphological comparison of interposed freeze-thawed skeletal muscle autografts and interposed nerve autografts in the repair of the rat facial nerve. AB - Freeze-thawed co-axially aligned skeletal muscle autografts provide a new concept in peripheral nerve repair, and are being investigated in the repair of mixed motor/sensory nerves. These grafts provide an orientated matrix of large basement membrane tubes through which regenerating axons can migrate and reinnervate the distal nerve. Using the buccal branch of the rat facial nerve as a model, we compared five freeze-thawed muscle autografts with five interposed nerve autografts. Some 300 days after grafting, the morphology of the distal nerve was evaluated. When the two groups were assessed morphometrically, it was found that nerve grafts showed a small but significant improvement over muscle grafts in respect of indices of the fibre maturation. PMID- 8365003 TI - Parental cigarette smoking and tonsillectomy in children. AB - The deleterious effects of parental smoking on the upper respiratory tracts of children are becoming increasingly recognized. This study examines the effect of parental smoking on the frequency of tonsillitis and incidence of tonsillectomy in children. A group of children being admitted for tonsillectomy and a control group of children from an orthoptic clinic were studied. Details recorded about the children included a history of tonsillectomy and the number of courses of antibiotics taken for sore throats in the previous 12 months. Parents were questioned about their smoking habits. A marked and statistically significant association has been found between the incidence of tonsillectomy in children and parental smoking in the home environment. There was a higher frequency of attacks of tonsillitis requiring antibiotic treatment in those children whose parents smoked. This effect may be mediated by altered oropharyngeal flora, mucociliary dysfunction, increased cross infection or a combination of these. If parents are encouraged to stop smoking there will be a reduction in tobacco smoke levels in the home environment and this should lead to a fall in both the incidence of tonsillitis and the need for tonsillectomy in their children. PMID- 8365004 TI - The assessment of alaryngeal speech. AB - The objective measurement of alaryngeal speech is desirable so that results between different centres can be compared. We examined several phonatory parameters of alaryngeal speech with the Visi-pitch and correlated these with the subjective assessment of voice quality. Amplitude, percentage voiced and perturbation correlated extremely well with the subjective assessment of voice quality. PMID- 8365006 TI - Conservative treatment of otitis media with effusion by autoinflation of the middle ear. AB - A total of 85 children on the waiting list for grommet insertion aged between 3 and 10 years with bilateral chronic otitis media with effusion (OME) were assigned at random to an observation or treatment group. Those in the treatment group were given the Otovent device to use three times a day for the duration of the study and both groups were then seen at monthly intervals for 3 months for pneumatic otoscopy and tympanometry. Statistically significant improvement was seen in those using the treatment with a compliance of more than 70%. This was detected on the outcome measures of tympanometry and pneumatic otoscopy after 1, 2 and 3 months. No side effects were demonstrated. We conclude that autoinflation is an effective short-term treatment for children with OME when used regularly under supervision. PMID- 8365005 TI - Blom-Singer prostheses--an 11 year experience of primary and secondary procedures. AB - Over the past 11 years, 25 primary and 29 secondary tracheo-oesophageal punctures have been performed in 51 laryngectomees. Pre-operative assessment is required for the secondary procedure. Both primary and secondary procedures require intensive speech therapy after fitting of the prosthesis. Fifty-four per cent of the primary and 37% of the secondary patients attained long-term speech, the latter figure rising to 58% with newer valves and increasing experience. Failures were commonly due to psychological or prosthesis-related problems. Complications were relatively minor, none being life threatening. Seventy per cent of the long term users were self caring. Adequate rehabilitation counselling and support is necessary to ensure long-term use of the prosthesis. PMID- 8365007 TI - Does the location of the laryngectomy stoma influence its ultimate size? AB - The stoma following laryngectomy may be placed either within the incision or separately. To determine if this variation had a bearing on its ultimate size, measurements of the stoma size were carried out in 61 patients who underwent laryngectomy by one of these methods. It was found that the stoma was nearly twice the size in patients in whom the stoma had been sited within the main wound and that there was a minimal need for the use of a tube or stoma button post operatively in these patients. PMID- 8365008 TI - Expression of the cell-cell adhesion molecule E-cadherin in squamous cell carcinoma of the head and neck. AB - The expression of the cell-cell adhesion molecule E-cadherin has previously been shown to be reduced in poorly differentiated squamous cell carcinoma of the head and neck and absent in nodal metastases. Twenty-eight patients with previously untreated squamous cell carcinoma of the head and neck, 22 of whom had nodal metastases at presentation, were investigated for E-cadherin expression using the monoclonal antibody 6F9, specific for human E-cadherin. Reduced expression was seen in the poorly differentiated primary tumours, compared with well differentiated tumours, but this trend was not statistically significant. E cadherin expression was present at a reduced level in nodal metastases. It was also noted that, where both the primary tumour and corresponding nodal metastasis were investigated, E-cadherin expression was identical for both samples. The degree of E-cadherin expression did not correlate with survival. These data confirm a reduction in E-cadherin expression in poorly differentiated tumours. There was no correlation between E-cadherin expression and any of the host, tumour and treatment factors associated with malignancies of the head and neck region. PMID- 8365009 TI - The influence of pathological and technical variables on hearing results in ossiculoplasty. AB - A prospective study of 55 ossiculoplasty operations has been carried out. Mean pre- and post-operative air-bone gaps and the changes in mean hearing loss were determined using the frequencies 500, 1000 and 2000 Hz. The influence of six potentially relevant variables on hearing results has been studied. Univariate analysis suggested that both the loss of the stapes arch and the presence of a mastoid cavity were associated with a significantly poorer outcome, but multi variate analysis confirmed this for loss of the stapes arch only (P = < 0.01). This is probably because the patients with open mastoid cavities more commonly suffered loss of the stapes arch (55%) than those with no cavity (27%) and had significantly larger air-bone gaps pre-operatively than those with no cavities (P = < 0.008). The results confirm the paramount importance of loss of the stapes arch as a determinant of outcome in ossiculoplasty and highlight the difficulties associated with trying to make valid comparisons between different patient groups undergoing this type of surgery. PMID- 8365011 TI - Laser treatment of rhinitis--1 year follow-up. AB - Laser cautery of the inferior turbinates for the treatment of rhinitis has been shown to be as effective as sub-mucosal diathermy in the short-term and to produce less morbidity. However, the long-term effects are unknown. A cohort of patients who were treated by either of these methods were reviewed 1 year after treatment. Subjective and objective measurements of airway obstruction were performed using a linear analogue scale and a nasal peak inspiratory flowmeter. The results obtained were compared with those recorded pre-operatively, 3 days post-operatively and 6 days post-operatively. In contrast to the results of sub mucous diathermy of the inferior turbinates for the treatment of rhinitis, the reduction in subjective nasal airway obstruction obtained by laser cautery to the inferior turbinates is maintained 1 year after surgery. Neither method of turbinate reduction was associated with a sustained objective improvement in nasal airway patency as measured by peak nasal inspiratory flow rate determinations. PMID- 8365010 TI - Adenotonsillectomy in patients with inherited bleeding disorders. AB - We describe the management of tonsil or tonsil and adenoid surgery in our hospital in 10 patients with inherited bleeding disorders, over a 10-year-period. The approach to the management of the haemostatic defect is outlined in detail. All underwent successful surgery, two patients had limited secondary haemorrhage. This report demonstrates that patients with inherited bleeding disorders can safely undergo adenotonsillectomy, providing there is close liaison between surgeons and haematologists throughout the peri-operative period. PMID- 8365012 TI - Eustachian tube function during pregnancy. AB - The upper respiratory mucosa has been reported to react to sex hormones in both physiological and pathological conditions. The present study was specifically aimed to determine the influence of high levels of oestrogen on Eustachian tube function. Fifty-three healthy, pregnant women were prospectively evaluated for Eustachian tube function during pregnancy. Eustachian tube function was found to be highly variable in different women, and in the same woman at different stages of pregnancy. We did not find a specific trend in Eustachian tube function with increasing oestrogen levels as encountered during pregnancy. PMID- 8365013 TI - Day case adenoidectomy. AB - The Audit Commission recommends that more day surgery be undertaken in the Health Service. In a prospective study of 62 children undergoing adenoidectomy one major complication commenced within 2 hours of surgery. Of 15 minor complications, 78% occurred within 6 hours of surgery; they did not herald later major complications. Day adenoidectomy can safely be performed if patients remain in hospital for 6-8 hours post-operatively and then fulfil the following discharge criteria: they are apyrexial, eating, drinking and with no signs of haemorrhage. This will not result in a significant increase in workload for general practitioners. Day adenoidectomy for medically and socially appropriate patients increases our day surgery figures by 74% to 43% of the routine paediatric ENT caseload. There are immediate benefits to patients but the potential economic benefits to the Health Service will not be felt unless these children are treated in a designated Day Case Unit. PMID- 8365014 TI - Validation of acoustic rhinometry by using the Cavalieri principle to estimate nasal cavity volume in cadavers. AB - The ability of acoustic rhinometry to provide valid estimates of nasal cavity volume has been tested using cadaveric heads. Values obtained for the cavities in five intact heads were compared with unbiased estimates of the volumes of the same specimens. An unbiased estimate is one which does not depart in a systematic manner from the true value. Here, unbiased estimates were made by applying the Cavalieri principle to uniform random samples of 4-7 macroscopic slices per specimen. Using acoustic rhinometry, the mean volume (left and right sides combined) amounted to 31.3 ml with a co-efficient of variation of 77%. On the same specimens, the Cavalieri estimate of mean volume (both cavities plus the adjacent nasopharynx) was 31.1 ml (66%). There was a significant and positive correlation between the two data sets (correlation co-efficient 0.97). Repeated acoustic measurements on the same cavities gave a measuring error of about 4%. We conclude that acoustic rhinometry can provide valid and efficient estimates of the volume of the nasal cavity plus nasopharynx. PMID- 8365015 TI - Sensory interaction posturography in patients with benign paroxysmal positional vertigo. AB - BPPV (benign paroxysmal positional vertigo) is a very common peripheral vestibular disturbance. The dysfunction becomes manifest mainly by vertigo and typical nystagmus. However, the vestibulospinal reflex (VSR) can also be disturbed. This can be shown by the SPGIII (static posturography type III), which is a platform technique evaluating 'sensory interaction' in a way comparable to that of the Equi-test. Half the patients with BPPV show disturbed posturographic results. By interfering with the sensory input of vision and/or proprioception, the separate contribution of each input can be evaluated. Different 'formulae' are seen, from complete normal results, through 'overall' formulae, i.e. an undifferentiated influence in all test-conditions, to specific formulae, where we find 'eye-closure' and 'head retroflexed'-effect and so-called 'vestibular formulae'. These formulae are an expression of the different degrees of compensation achieved by the centres and especially of the 'substituting' compensation by vision and proprioception. These results confirm that posturography does not provide a typical results-pattern, thus the type of peripheral vestibular disorder cannot be diagnosed by it alone. The results give functional information on how the standing position is achieved in these patients with a disturbed VSR-input. The several formulae prove that indeed different compensatory patterns are possible, as has been shown by experiments on vestibular compensation. PMID- 8365016 TI - Fish bones and other foreign bodies. AB - In this prospective study the types of foreign body ingested, sites of impaction, radiographical findings, management and outcome in 81 patients were recorded. We have demonstrated that foreign bodies can be conveniently divided into 'fish bones' and 'others', in terms of their sites of impaction (P < 0.0001), the age groups affected, whether dentures were worn or not (P < 0.02) and their respective management (P < 0.001). Statistical analysis supporting these observations has not been previously reported. PMID- 8365017 TI - Long-term effects of otitis media with effusion on language, reading and spelling. AB - The long-term effects of early OME on language and educational attainment were studied in 47 children of 7-8 years of age who had participated in an earlier pre school study on otitis media with effusion (OME) and language development. At pre school age OME was diagnosed by quarterly tympanometric screens (maximum nine) and language was assessed by a standard Reynell test. At school age the ears of the children were assessed by otomicroscopy, tympanometry and audiometry, and the development status by several language, reading and spelling tests. The association between early OME and language development found at pre-school age was no longer present at school age. PMID- 8365018 TI - ANCA in diseases other than systemic vasculitis. PMID- 8365019 TI - Treatment of autoimmune diseases with normal immunoglobulin through manipulation of the idiotypic network. PMID- 8365020 TI - Mechanisms of neutrophil-mediated injury. PMID- 8365021 TI - The fate of the neutrophil in vasculitis. PMID- 8365023 TI - The endothelial cell: active participant or innocent bystander in primary vasculitis? PMID- 8365022 TI - Lymphocyte-vascular endothelial cell interactions in the immune response. PMID- 8365025 TI - Bullous diseases. Introduction. AB - The bullous diseases have a history as old as that of medicine. Although blisters have drawn the attention of medical caregivers throughout written history, only modern times have seen the origin of a clear classification of these disorders, based initially upon clinical and histologic criteria. Recent work has allowed clear delineation between similar diseases based upon localization of immune reactants and, more recently, molecular targets of autoimmune response or defects of inherited diseases. With a clear understanding of the clinical findings, histologic alterations, immune deposits, and metabolic defects, a clinician can arrive at a correct diagnosis in almost all cases of cutaneous blistering. The application of molecular biology to the study of bullous diseases has led to a more detailed understanding of the pathogenesis of the disorders. New horizons in the bullous diseases include further understanding of the molecular and immunologic mechanisms that lead to blisters. It is hoped that this understanding will lead to exciting new therapies and hope for patients suffering with blistering diseases. PMID- 8365024 TI - The clinical relevance of ANCA in vasculitis. PMID- 8365026 TI - The humoral immune response in autoimmunity. AB - Only within the last 5 years have data on variable region sequences of autoantibodies begun to accumulate. Although it is too early to draw final conclusions, certain principles are beginning to emerge. It is clear that self recognition by the immune system is normal. This fact is supported by the anti idiotype network and the presence of natural autoantibody in normal sera. Furthermore, there appears to be a connection between these phenomena because the former may serve to keep the latter in check. Natural autoantibody appears to be primarily IgM polyreactive antibody of low affinity, quite different from the monospecific high-affinity IgG antibody usually associated with autoimmune disease. Natural autoantibodies also exhibit a high degree of cross-reactive idiotypes and are the products of CD5+ B cells, whereas IgG autoantibody is not. This is only a generalization, however, and it must be kept in mind that IgG autoantibody polyreactive with several autoantigens has been reported for normal sera of mice and humans. In Balb/c sera, a significant proportion of natural autoantibody is IgG, but it is apparently masked by inhibitory polyreactive IgM antibody that has affinity for IgG autoantibody, thereby exhibiting a regulatory role. A human CD5+ B-cell clone that secretes a high-affinity IgM anti-idiotype specific antibody has been reported. Another generalization that is beginning to emerge is that natural autoantibodies are the products of unmutated germline genes, whereas autoantibody associated with autoimmune disease has highly mutated VH and VL segments. Mutations exhibited by pathogenic autoantibody increase the antibody's affinity for autoantigen and therefore represent an antigen-selected or affinity maturation, resulting in more restricted heterogeneity. In contrast to this, polyreactive natural antibodies have variable regions that are essentially identical to germline gene V segments with few amino acid changes. However, it is important to note that pathologic autoantibodies arise from the same fetal genes that give rise to natural autoantibodies and antibodies against foreign antigens. There does not appear to be a set of genes specific for autoantibodies. The key question then becomes whether or not natural autoantibodies are precursors of pathogenic autoantibodies. If not, what is the function of natural autoantibodies and how do pathogenic autoantibodies arise? The answers to these questions are not yet clear and many theories have been offered, but sufficient data are not yet available to reach conclusions. One of the problems in reaching a definitive conclusion is the ability to identify pathogenic antibody.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8365027 TI - MHC regulation of immune responses. AB - The major histocompatibility complex is a group of complex genes situated on the short arm of chromosome 6 in humans. They play an important role in the regulation of the immune response. Autoimmune blistering disease provides an ideal model for studying the role of MHC in autoimmunity. The diseases are organ specific, and in some of them the relevant antigen has been cloned and sequenced. Such information on the antigen will help further define the interactions of the Ag, MHC, and TCR. Use of family studies hopefully will define and localize susceptibility alleles, so that any genetic susceptibility can be identified at the molecular level. It is from these molecular perspectives that molecular therapies could be assigned to restore the immune system. PMID- 8365028 TI - Established methods in the investigation of bullous diseases. AB - We have discussed an approach to the diagnosis of bullous diseases based on available and established methods. We highlighted the clinical features that help distinguish the various diseases. We then outlined a histopathologic pattern approach to the differential diagnosis and extensively discussed the value of immunofluorescence in the diagnosis of bullous diseases. PMID- 8365029 TI - New laboratory methods in the investigation of bullous disease. AB - Over the last 5 to 10 years, basic research in the areas of cell biology, biochemistry, immunology, and molecular biology has led to quantum advances in our understanding of the causes of the bullous diseases. This explosion of new information has been made possible by corresponding technologic advances related to these scientific disciplines. This article does not represent a comprehensive review of this topic, but rather highlights important contributions primarily from the field of molecular biology. Much of this article describes research technologies aimed at identifying and characterizing the genes and gene products that are directly involved in the pathogenesis of the bullous disorders. Although many significant advances have been made, a great deal remains to be done. It is our hope that the next 5 to 10 years will witness the emergence of a new set of technologies that will facilitate the translation of this new-found molecular information into more accurate diagnostic tools, more effective therapeutic strategies, and a fuller understanding of the basic biology of the skin. PMID- 8365030 TI - Pemphigus vulgaris and vegetans. AB - Pemphigus vulgaris, which has multiple clinical variants, is an autoimmune blistering disorder of skin and mucous membranes, usually affecting the elderly, with a strong immunogenetic link. Immunologic studies of this disease have been productive in defining the pathophysiology of blister formation and the characteristics of the pemphigus antigen. New therapies resulting from the newest research techniques would prevent the global immunosuppression that occurs during drug therapy with systemic glucocorticoids, which is the cornerstone of therapy for patients afflicted with this potentially life-threatening disorder. PMID- 8365031 TI - Endemic pemphigus foliaceus. Fogo selvagem. AB - Fogo selvagem is a form of pemphigus foliaceus indistinguishable on clinical, histologic, immunofluorescence, and ultrastructural grounds from sporadic pemphigus foliaceus found in North America and Europe. It can, however, be distinguished on epidemiologic grounds by its unique geographic distribution. The association of FS with its environment is supported by its limited areas of predilection, that is, between 500 and 800 meters altitude near rivers, and the remission of the disease when patients are removed from this environment. Owing to its obvious environmental trigger, FS may serve as a model for the initiation of autoimmune phenomena. We need merely to find the specific trigger or triggers, and the search is now under way. PMID- 8365032 TI - Drug-induced pemphigus. AB - Drug-induced pemphigus is a heterogenous group of disorders in which a drug induces acantholysis. The majority of patients have immune features of pemphigus and have a course similar to idiopathic pemphigus. Few patients do not have a detectable autoimmune process, and their eruption usually resolves with discontinuation of the associated drug. The mechanism of induction of the autoimmune process and acantholysis is not clear. PMID- 8365033 TI - Paraneoplastic pemphigus. AB - Paraneoplastic pemphigus is a newly recognized disease that occurs in some patients with lymphoproliferative neoplasms and occasionally, solid tumors. Patients present with an acute illness of the mucosa and skin that shares clinical and histologic features with erythema multiforme, toxic epidermal necrolysis, and pemphigus vulgaris. These patients have antibodies against a complex of epithelial proteins that are present in desmosomes and hemidesmosomes. The course is usually fatal, except in some patients who undergo total resection of their neoplasm. PMID- 8365034 TI - Bullous pemphigoid. AB - Bullous pemphigoid is an acquired subepidermal blistering disease of the elderly characterized by tense blisters. Patients with bullous pemphigoid have circulating and tissue-bound antibodies that are directed against a normal component of the epidermal basement membrane. The course of bullous pemphigoid tends to be self-limited, and effective treatment is often affected with systemic glucocorticosteroids. PMID- 8365035 TI - Cicatricial pemphigoid. AB - Cicatricial pemphigoid presents with oral or ocular inflammation and blisters that are followed by scarring. The differential diagnosis of cicatricial mucositis includes other subepithelial blistering disorders. The disease is usually chronic and can be associated with high morbidity. Treatment of severe cases with immunosuppressive agents is usually helpful. PMID- 8365037 TI - Herpes gestationis. AB - HG expresses a broader clinical range than previously thought. Disease may be mild and nonvesicular during one pregnancy, followed by explosive vesiculobullous disease during another. On the other hand, patients with extensive HG during one pregnancy may experience mild or even subclinical disease during a subsequent gestation. The broad range of clinical signs and the lack of demonstrable fetal or maternal risk associated with HG have important ramifications for patients desirous of further children. There is a genetic predisposition to HG. DRB1*0301 (HLA-DR3) is increased and 90% of patients express either DRB1*0301 (HLA-DR3) or DRB1*0401/040X (HLA-DR4). Ninety percent of patients also carry a C4 null allele, which may be due to linkage dysequilibrium with DRB1*0301 or DRB1*0401/040X. The disease appears to be mediated by an IgG1 specific for a 180-kD component of hemidesmosomes. This protein is distinct from the 240-kD hemidesmosomal antigen seen in BP and is coded for by a different cDNA on a different chromosome. Abnormal expression of class II MHC occurs in the placental villi of those with HG, suggesting ongoing immunologic stimulation. This has led some investigators to believe that the primary immunologic event is taking place within the placenta and that the skin is an immunologic bystander. PMID- 8365036 TI - Dermatitis herpetiformis and linear IgA bullous dermatosis. AB - DH is an uncommon vesicular disease of the skin which has attracted great interest because of myriad clinical and laboratory findings believed to be related to its immunopathogenesis. Investigations have centered on its relationship to gluten intake, multisystem disease associations, pathognomonic patterns of IgA deposition, and impressive therapeutic response to gluten restriction and dapsone. However, a coherent theory of pathogenesis has not yet been established. The circulating antibody responsible for the IgA deposition has not yet been identified, and indirect IF is negative. LABD has now been separated from DH on the basis of its unique immunopathologic finding of linear IgA along the cutaneous basement membrane and the presence of circulating IgA anti-basement membrane antibody, which binds to a 97-kD protein found in normal human skin. It has been suggested that CBDC and LABD are expressions of the same disease process in different age groups rather than two distinct disease processes. Supporting evidence for this theory is based on immunopathologic findings. Linear deposition of IgA along the basement membrane of perilesional skin is identical to LABD and, in addition, a circulating IgA anti-basement membrane antibody is present in the serum of some patients which binds to the 97-kD antigen described in LABD. PMID- 8365038 TI - Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. AB - Autoimmunity to C7 is a genetically predisposed condition that results in the production of predominantly IgG class basement membrane autoantibodies that may cause basement membrane damage and subepidermal blisters by at least two pathogenic mechanisms. Autoimmunity to C7 cuts across traditional disease classifications (EBA versus bullous SLE), presents with heterogeneous clinical and pathologic features, mimics other diseases, and may be difficult to diagnose and treat. Autoimmunity to C7 is associated with susceptibility to SLE and perhaps inflammatory bowel disease. PMID- 8365039 TI - Inherited epidermolysis bullosa. Clinical features, molecular genetics, and pathoetiologic mechanisms. AB - Recent advances in the molecular biology of the extracellular matrix have resulted in a detailed understanding of the cutaneous basement membrane zone. Consequently, the application of this information to the study of the molecular genetics of the genodermatoses has resulted in spectacular success in the last few years. This article summarizes progress made in the molecular biology of the cutaneous basement membrane zone and its impact on understanding the basis of heritable blistering diseases of the skin, with particular emphasis on epidermolysis bullosa. PMID- 8365040 TI - Inflammatory bullous diseases in children. AB - Bullous disease in children can be confusing clinically and challenging to mange. Five groups of autoimmune bullous disease are discussed with emphasis on unique features in children. Pemphigus (vulgaris, foliaceus, neonatal), pemphigoid (bullous and cicatricial), dermatitis herpetiformis, linear IgA dermatosis, and epidermolysis bullosa acquisita are uncommon pediatric disorders. A high index of suspicion is necessary to diagnose and treat these conditions without delay. PMID- 8365041 TI - The porphyrias. AB - The vesiculobullous porphyrias are a group of blistering diseases with systemic as well as cutaneous manifestations ranging from mild to disabling, secondary to endogenous photosensitizing porphyrins. The characteristic patterns of porphyrin accumulation in erythrocytes, plasma, urine, and feces are invaluable for differentiating the vesiculobullous porphyrias from other blistering diseases and from one another. Most importantly, these porphyrin profiles are essential for distinguishing the acute vesiculobullous porphyrias, HCP and VP, from PCT, which is not associated with acute attacks. This distinction may prevent the potentially fatal administration of porphyrinogenic drugs to patients with HCP or VP. Histopathology is not helpful in differentiating the vesiculobullous porphyrias, as all typically show subepidermal bullae. Avoidance of sun exposure and precipitating factors are the initial steps in both the prevention and treatment of these entities. In addition, more specific therapy may be indicated, as discussed in the preceding pages. PMID- 8365042 TI - Bullous dermatoses associated with systemic disease. AB - The bullous diseases that are neither immune-mediated nor inherited form a heterogeneous group that may be classified according to their major histopathologic characteristics. Such a classification allows clear distinctions to be made between entities that may have clinical similarities such as staphylococcal scalded skin syndrome, toxic shock syndrome, erythema multiforme/toxic epidermal necrolysis, and acute graft-versus-host disease. Proper differentiation of these entities is critical for their study and for appropriate management. PMID- 8365043 TI - Topical immunotherapy in the treatment of chronic severe alopecia areata. AB - In the past decade, topical immunotherapy with DPCP has been shown to be a very important therapeutic modality in the treatment of chronic severe alopecia areata. At the University of British Columbia Hair Clinic, it is our treatment of choice in adults. This option for treatment should be offered to the appropriate patients. PMID- 8365044 TI - Topical immunotherapy of alopecia areata. AB - Topical immunotherapy has proven to be a highly rewarding treatment modality for extensive forms of AA. The method should be considered at this time to be in an experimental stage, and therefore hesitation to adopt it is understandable. However, other acceptable and effective modes of treatment are thus far lacking. Extensive AA is not merely a cosmetic problem. Affected individuals often experience a considerable subjective loss of quality of life, and in such cases topical immunotherapy should be considered. PMID- 8365045 TI - Morphology of resistance arteries and comparison of effects of vasoconstrictors in mild essential hypertensive patients. AB - We have compared the response of small subcutaneous resistance arteries from 15 mild essential hypertensive patients and 13 normotensive controls to various potentially pathophysiologically important vasoconstrictors. Blood vessels obtained from gluteal subcutaneous biopsies from hypertensive patients exhibited a significantly smaller external diameter and lumen and greater media/lumen ratio than those of normotensive subjects, but no significant difference in media thickness or cross-sectional area. Vasoconstrictor peptides produced varying effects on resistance arteries of hypertensive patients relative to controls: angiotensin II and arginine vasopressin elicited normal active media stress responses, while the contractile effect of endothelin-1 was depressed. Norepinephrine media stress responses were also blunted in hypertensive patients. Cocaine produced a shift to the left of the norepinephrine dose-response in vessels from both controls and hypertensive patients. Since the lumen diameter of blood vessels was reduced in hypertensive patients, vasoconstrictor responses were amplified, resulting in calculated pressor responses to endothelin-1 similar to those of normotensive controls. These results demonstrate the structural and functional alterations present in resistance arteries of mild essential hypertensive patients, which may be involved in maintaining elevated blood pressure. PMID- 8365046 TI - Intestinal permeability compared in pediatric and adult patients with inflammatory bowel disease. AB - Increased urinary excretion of 51Cr-EDTA after oral administration has been demonstrated in adults with active inflammatory bowel disease (IBD). Pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC) were compared to pediatric and adult controls and adult patients with IBD using this technique. Seventy-five pediatric IBD patients, 51 (mean age 13.8 y) diagnosed with active CD and 24 (mean age 11.9 y) with active UC, were examined. These were compared to 26 pediatric controls with recurrent abdominal pain or chronic non-specific diarrhea. Further comparison was made to 80 adult controls (mean 32.0 y), 63 adults with active CD and 31 adults with active UC. After an overnight fast, 925 kBq of 51Cr-EDTA was given orally and urine collected for 24 h. Excretion of the probe by the pediatric controls and adult controls was 1.5%/24 h and 1.3%/24 h (median), respectively. Of the pediatric patients, 45/51 (88.2%) with active CD (median 3.9%/24 h) and 16/24 (66.7%) with active UC (median 4.8%/24 h) showed increased excretion. Pediatric patients with active IBD demonstrated increased probe excretion comparable to levels of adult patients. In the pediatric population, accuracy of the first test was 83.0%. Thus, urinary excretion of 51Cr EDTA is a useful non-invasive test in the investigation of pediatric patients with gastrointestinal symptoms. PMID- 8365047 TI - Plasma beta-endorphin concentration and xanthine treatment in apnea of prematurity. AB - Apnea of prematurity is a common problem in neonatal intensive care nurseries. Xanthines are used to treat apnea, but their mechanism of action is not clearly understood. To determine whether xanthines stimulated beta-endorphin (beta-ED) release in preterm infants, plasma beta-ED concentrations were measured in 27 infants with apnea of prematurity. These infants had a mean (+/- SD) birthweight of 1560 +/- 487 g, gestational age 31 +/- 2.5 weeks, and a postnatal age of 7.3 +/- 4.6 d. Twenty-five of the infants were treated with I.V. aminophylline 2.5 mg/kg/dose 4 times daily and 2 were treated orally with caffeine (10 mg/kg). Blood samples were collected prior to and 30 min after treatment with xanthines. Apneic spells greater than 15 sec were recorded and reviewed every 24 h using a Hewlett-Packard Merlin Monitor (Waltham, MA.) system. Infants were then stratified into responders (Group 1, n = 14) and nonresponders (Group 2, n = 13), with responders defined as showing more than 50% decrease in the frequency of apneic spells in the first 24 h of treatment. beta-ED were measured as previously described using a radioimmunoassay technique. In group 1, plasma beta-ED concentration increased significantly, (p = 0.0496) from pre-xanthine (24.4 +/- 12 pg/ml) to post xanthine (34.6 +/- 24 pg/ml) treatment, whereas in Group 2 the concentrations remained the same (23.3 +/- 5 pg/ml) and (22.6 +/- 4 pg/ml). Birthweight, gestational age, postnatal age, and diagnoses in both groups were compared and no significant differences were observed. Interestingly, xanthine treatment caused increased plasma beta-ED release when apneas decreased. PMID- 8365048 TI - Whey proteins as a food supplement in HIV-seropositive individuals. AB - On the basis of numerous animal experiments, a pilot study was undertaken to evaluate the effect of undenatured, biologically active, dietary whey protein in 3 HIV-seropositive individuals over a period of 3 months. Whey protein concentrate was prepared so that the most thermosensitive proteins, such as serum albumin which contains 6 glutamylcysteine groups, would be in undenatured form. Whey protein powder dissolved in a drink of the patient's choice was drunk cold in quantities that were increased progressively from 8.4 to 39.2 g per day. Patients took whey proteins without adverse side effects. In the 3 patients whose body weight had been stable in the preceding 2 months, weight gain increased progressively between 2 and 7 kg, with 2 of the patients reaching ideal body weight. Serum proteins, including albumin, remained unchanged and within normal range, indicating that protein replenishment per se was not likely the cause of increased body weight. The glutathione content of the blood mononuclear cells was, as expected, below normal values in all patients at the beginning of the study. Over the 3-month period, glutathione levels increased in all 3 cases. In conclusion, these preliminary data indicate that, in patients who maintain an adequate total caloric intake, the addition of "bioactive" whey protein concentrate as a significant portion of total protein intake increases body weight and shows elevation of glutathione (GSH) content of mononuclear cells toward normal levels. This pilot study will serve as a basis for a much larger clinical trial. PMID- 8365049 TI - An animal model of foodborne Listeria monocytogenes virulence: effect of alterations in local and systemic immunity on invasive infection. AB - Development of foodborne listeriosis is dependent on an interplay between organism-specific virulence factors and host susceptibility. Gastric inoculation of Sprague-Dawley rats was used as a model to explore Listeria-specific virulence and host susceptibility. Gastric inoculation leads to invasive infection with "smooth" hemolytic Listeria monocytogenes but not with "rough" L. monocytogenes or other Listeria species. Infection is dose-dependent with an ID50 of 10(6) virulent Listeria monocytogenes. In these experiments, the ID50 was not altered by pregnancy but invasive infection led to abnormal reproductive outcomes including stillbirth and reabsorption of fetuses. Immunosuppression by cyclosporin A led to more prolonged infection but did not alter the ID50. Manipulation of intestinal flora with antibiotics suggested increased rates of infection with antibiotics that decreased anaerobic flora. Growth of virulent Listeria in milk at varying temperatures did not enhance virulence. No differences in invasive potential of flagellated vs. non-flagellated L. monocytogenes were found. Oral models of invasive Listeria monocytogenes infection provide a useful tool for studying organism virulence and host susceptibility. PMID- 8365050 TI - Effects of immunosuppressive therapy on hepatic expression of hepatitis B viral genome and gene products. AB - To determine the effect of immunosuppressive therapy on hepatic expression of hepatitis B virus (HBV) DNA and antigens in vivo, serial biopsies from 12 patients with chronic active hepatitis B who had been given immunosuppressive therapy (prednisolone 10-15 mg +/- azathioprine 75-125 mg daily) in an earlier period were studied using immunohistochemistry and non-isotopic in situ hybridization. Four out of the 12 patients were positive for hepatic HBcAg/HBeAg/HBV DNA before immunosuppressive therapy. In these 4 patients positive for HBcAg, there was an increase in staining intensity and the proportion of liver cells positive for both HBcAg/HBeAg/HBV DNA and HBsAg during therapy. Of the 8 patients negative for hepatic HBcAg/HBeAg/HBV DNA before immunosuppressive therapy, hepatic HBcAg, HBeAg, and HBV DNA were detected in 2 patients, along with stronger and more diffuse hepatic expression of HBsAg. The other 6 patients also had an increase in hepatic HBsAg expression but without HBcAg. These data provide in vivo evidence that in some patients, immunosuppressive therapy enhances hepatic expression of both HBV genome and gene products. PMID- 8365051 TI - Clinical research: any future? AB - Laboratory-based clinical research is in a severe crisis in Canada. The reasons are many and range from the serious inadequacy in the financial remuneration of research fellows going to the USA. or Europe for further training to the overpowering trend to seek solutions to clinical problems directly at the molecular and cellular levels instead of the traditional physiopathological approach. The language of molecular biology and genetics, with its innumerable acronyms, is quite foreign to clinical medicine. In addition, molecular biology research leaves little time for clinical care of patients. Steps should be taken to reinvigorate laboratory-based clinical research since it is the key transfer point of basic advances to clinical care. Fellowships of the order of $50 to $60,000 to research fellows going to the United States or abroad should be provided. Close collaboration between PhD scientists and clinical scientists, as so successfully achieved at the Clinical Research Institute of Montreal in the last 25 years, should be emphasized, and a greater percentage of funds from research agencies should be designated for the support of laboratory-based clinical research and for the training of clinical scientists. PMID- 8365052 TI - [Magnetic resonance imaging in chronic toluene abuse, and volitional hyperkinesia]. AB - We described the central nervous system impairments and findings of magnetic resonance imaging (MRI) of the brain in three chronic toluene abusers. Patient 1 and 2 had a history of chronic toluene inhalation for 1 or 2 years and patient 3 has a history of it for 16 years. The patients were evaluated after an abstinence period of at least 4 weeks, to avoid neurologic effects of acute intoxication. Neurologic signs included cerebellar, cognitive and pyramidal dysfunctions in all 3 patients and hyperkinesie volitionnelle (HV; volitional hyperkinesia) in patient 3 who had a long history of toluene inhalation. This HV was found to be tremulous by surface electromyography. Appearance of HV in chronic toluene abuse seems to be related to a period or quantity of inhalation of toluene. T2-weighted MRI in the 3 patients revealed the following abnormalities: (1) increased signal intensity of middle cerebellar peduncle and cerebellar white matter, deep cerebral white matter, and posterior limb of internal capsule; and (2) decreased signal intensity of thalamus and basal ganglia. Proton-weighted MRI in patient 3 with HV showed decreased signal intensity of lateral portion of the thalamus and tegmentum of the brainstem. These MRI findings correlate remarkably well with the neurologic signs seen in the 3 patients. Cerebellar, cognitive, and pyramidal dysfunctions appear to be related to involvement of middle cerebellar peduncle (cerebellar white matter), deep cerebral white matter, and internal capsule, respectively, and HV seems to correlate with involvement of the thalamus or tegmentum of the brainstem, especially the latter. PMID- 8365053 TI - [Saccadic eye movement related scalp potentials--scalp distribution of presaccadic slow negative potential]. AB - We studied scalp distribution of presaccadic slow negative potential (PSN) among saccadic eye movement related scalp potentials in 17 normal subjects performing self-paced voluntary saccades in light (VS). There was a widespread PSN beginning at 1400 msec prior to saccades, maximum at the vertex. Amplitudes of PSN were greater over frontocentral electrodes contralateral to the direction of the saccades. These findings are consistent with reflection of activation of the supplementary motor area, and the frontal eye field contralateral to the direction of the saccades. On the other hand, amplitudes of PSN were relatively greater over occipital electrodes ipsilateral to the direction of the saccades. In addition, we studied PSN in 6 normal subjects performing self-paced voluntary saccades in darkness (VSD). PSN with VSD did not extend to occipital electrodes in comparison with PSN with VS. Occipital component of PSN with VS may reflect activation of other cerebral cortices which relate to visual inputs. PMID- 8365054 TI - [Early-onset parkinsonism with diurnal fluctuation--clinical and pathological studies]. AB - The literature regarding parkinsonism of early-onset indicates that it encompasses several diseases differing in their clinical and pathological features. Since 1968 we have reported cases of early-onset parkinsonism with diurnal fluctuation of symptoms (abbrev. as EPDF). Attention has been focused on its similarities to or differences from Parkinson's disease (PD), juvenile parkinsonism of Yokochi, and hereditary progressive dystonia (HPD) of Segawa et al. In this paper we report the clinical and pathological characteristics of EPDF to facilitate its nosological identification. We examined the pathological features of EPDF in two cases. Case 1 was a 52-year-old female with consanguineously related parents and two other affected sisters. The disease began at the age of 20, and she had marked diurnal fluctuation of symptoms. With the assistance of L-dopa and bromocriptine, she was able to enjoy relatively satisfactory daily life activity until the age of 50. In the last two years she was bed-ridden with advanced parkinsonism. Case 2 was a 56-year-old man without any contributing family history. His disease started at age 26 and his symptoms showed slight fluctuation during the earlier stages of the disease. Treatment with L-dopa and bromocriptine was associated with marked up-and-down phenomenon and choreatic dyskinesia. Pathological study in the two cases revealed marked cell loss in the substantia nigra zona compacta, especially in the area A9, while the neuronal cell population of the ventral tegmental area (A10), locus caeruleus, superior raphae nucleus, and substantia innominata was relatively well preserved. There were no Lewy bodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365055 TI - [An autopsied case of intravascular malignant lymphomatosis with paraparesis, that presented a leukoencephalopathy-like image after spinal cord biopsy]. AB - A 54-year-old woman was hospitalized because of paraparesis, sensory disturbance of the lower extremities, and dysuria. Laboratory data included an erythrocyte sedimentation rate (ESR) of 16 mm/h and lactate dehydrogenase (LDH) level of 459 IU/l. Myelogram showed an enlarged spinal cord at the L1 level, and spinal MRI revealed a high signal area on T2-weighted images. Spinal cord biopsy by thoraco lumbar laminectomy showed thickening of the pia mater and neovascularization, but no malignant cells. Immediately after the operation, the patient displayed progressive mental deterioration. Cranial MRI showed widespread high signal areas in the cerebral white matter on T2-weighted images which resembled those of leukoencephalopathy. Steroid therapy was tried but was ineffective. Ten months after the onset of symptoms, a brief period of regression of both clinical symptoms and MRI appearances occurred following the administration of Inosiplex, subsequent progressive deterioration led to death 14 months after the onset of symptoms. LDH, C-reactive protein (CRP), and cerebrospinal fluid (CSF) protein were all elevated during the deterioration of her general status. Postmortem examination revealed a large tumor mass of the left adrenal gland which extended to the Th12, L1, and L2 vertebrae and remarkable brain edema. Microscopic mononuclear tumor cells were widespread but confined to the lumens of small vessels of the brain, spinal cord, spinal root and right adrenal gland, almost as if they were occluded. Cerebral white matter presented widespread multiple small infarcts and extensive myelin thinning. In addition to the left adrenal gland, interstitial invasions of tumor cells were discovered in the kidneys, iliopsoas muscles, oviducts, myocardium, lymph nodes, and thyroid gland.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365056 TI - [Familial cases of spastic paraparesis, mental disturbance and thinning of the corpus callosum]. AB - We reported a family in which two brothers and one sister out of five siblings were affected by a neurological disease showing the following clinical manifestations: 1) intellectual disturbance with relative preservation of memory and orientation probably developed on child food, 2) spastic paraparesis beginning at the age of about 20 years, 3) mild peripheral neuropathy and cerebellar sign. Their clinical courses were stereotyped, and so much the worse in elder patients. Two of them were investigated in detail. Laboratory findings including chromosomal analysis, amino acid analysis and thyroid function were normal. HTLV-1 antibody was negative. Several lymphocytes lysosomal enzymes including beta-hexosaminidase and arylsulfatase A and serum very long fatty acids were also within normal range. CT and MRI showed characteristic thinning of corpus callosum, dominant in anterior portion. However, changes in intensity of white matter in T2 weighted image were not so prominent. In the older patient, more mentally deteriorated, were demonstrated hypoperfusion in the fronto parietal lobes by SPECT and slow wave bursts dominant in the same region by EEG. Therefore, we considered that the change of corpus callosum was hypoplasia, but not atrophy, and it may provoke dysfunction of relevant nervous system. Family cases of such clinical feature were rare. We could confirm only three families in literatures, all of them were Japanese. PMID- 8365057 TI - [A case of X-linked recessive bulbospinal muscular atrophy with demyelinating neuropathy and hypertrophy of the calves]. AB - We report a 53-year-old man of X-BSMA with neuropathy. The patient developed slowly progressive muscular weakness and wasting over a 2-year period with an accompanying numbness in the finger tip. He can run normally but not so fast. When he was aged 52-year old, difficulty in running progressed. General physical examination revealed nothing particular except for hypertension and gynecomastia. He showed muscular weakness and atrophy in the tongue, shoulder girdle, and upper and lower limbs. Calf muscle hypertrophies were prominent on both sides. The tendon reflexes were absent. Slight sensory impairment for vibration and pin prick was present distally in all limbs. Autonomic nerve dysfunction was not observed. Hyperglycemia, elevated HbA1c and elevated serum CK (1,242 IU/l) were seen. The computed tomographic analyses on skeletal muscle showed hypertrophic changes in the calf muscles with a few fatty infiltrations. Electromyography showed a systemic neurogenic pattern. Motor nerve conduction velocities were slightly delayed in the lower limits. Sensory nerve action potentials were not elicited in all nerves tested. Sural nerve biopsy disclosed marked reduction of myelinated fibres for that of large diameter with thin myelin. Teased fibre studies showed a definite increase in the incidence of fibres with segmental demyelination and remyelination. In electron microscopic examination, typical or atypical onion bulb formation was observed on individual fibres. Axonal changes were minimum. We believe that segmental demyelination observed in this patient is not secondary to axonal damage. We, also, investigated AR gene abnormality by polymerase chain reaction (PCR) in this patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365058 TI - [A case of hereditary motor and sensory neuropathy type I with optic atrophy, neural deafness and pyramidal tract signs]. AB - A case of hereditary motor and sensory neuropathy (HMSN) type I with optic atrophy, neural deafness and pyramidal tract signs was described. The patient was a 53-year-old man who had suffered from difficulty in walking, decreased visual acuity since age 16 years. These symptoms were slowly progressive. At the age of 37, he was pointed out optic atrophy, positive pyramidal tract signs. Distal muscle weakness with atrophy of four limbs was prominent at the age of 50. Since then, he noticed progressive hearing loss with blindness. His elder sister was diagnosed Charcot-Marie-Tooth disease. On neurological examination, he showed to have optic atrophy without retinitis pigmentosa and neural deafness. Also he showed mild degree of muscle weakness and atrophy in four limbs, severe in the distal part of lower limbs. Deep tendon reflexes were absent in all limbs with right Babinski sign. Superficial sensation was decreased slightly in the distal parts of four limbs. Deep sensation was markedly decreased in the leg. There were no cerebellar signs. Audiometric examination revealed bilateral neural hearing loss. There were no findings of spinal cord compression on spinal MRI. On the nerve conduction studies, sensory nerve action potential was not elicited in all nerves tested. Motor nerve conduction velocity of the right median was 41.1 M/sec, also ulnar nerve 44.7 M/sec, but M-wave was not elicited with the electrical stimulation of other tested nerves. On sural nerve biopsy, the density of myelinated fibers was severely decreased. Well-myelinated axon surrounded by onion bulb formation was observed in electron microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365059 TI - [A case of Hallervorden-Spatz syndrome with marked atrophy of the brainstem and cerebellum]. AB - We report a 20-year-old female with Hallervorden-Spatz syndrome (HSS). This patient is the product of consanguineous parents. She developed genu valgum, tendency to fall and mental deterioration at the age of 6, decrease of the number of spoken words at the age of 14, dysarthria, unsteady gait, postural tremor of the upper extremities, dystonic posture of hands and double incontinence at the age of 16. Her disease progressed slowly. Neurological examination on admission revealed severe mental retardation, optic atrophy, forced grasping, hyperactive tendon reflexes in the upper extremities and bilateral Babinski sign. An extensive laboratory investigation including the leukocyte lysosomal enzymes, serum amino acid analyses, copper studies and ceruloplasmin were almost within normal limits. MRI, T2 weighted images, showed markedly decreased signal intensity in the globus pallidus but substantia nigra and increased signal intensity in diffuse cerebral white matter. T1 weighted images showed marked atrophy of the brainstem and cerebellum. She met the diagnostic criteria for HSS by Swaiman; we diagnosed her as HSS group II. HSS is characterized by the presence of many spheroids in the central nervous system which is similar to neuroaxonal dystrophy (ND). However, clinical and pathological differences exist between HSS and ND, the precise classification of the two conditions has remained controversial. Although there are many reported cases in which both conditions overlap, this is the first reported case that simultaneously demonstrates increased iron deposition in the globus pallidus, marked atrophy of the brainstem and cerebellum and typical clinical course compatible with HSS. PMID- 8365060 TI - [A case of Wernicke-Korsakoff syndrome caused by gastrojejunostomy--specific findings of MRI and SPECT]. AB - A 63-year-old woman with Wernicke-Korsakoff syndrome, despite the absence of alcoholism and malnutrition, is reported. She had undergone gastrojejunostomy for ileus 30 years ago, and this operation was thought to be an important risk factor for her vitamin B1 deficiency. Brain MRI showed symmetrical high intensity areas on T2-weighted images in the periaqueductal region and bilateral dorsomedial nuclei of the thalamus. On single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime, bilateral frontal perfusion was reduced, which was attributed to thalamo-cortical diaschisis due to injury to the dorsomedial nuclei of the thalamus. Presumably this phenomenon explains the Korsakoff psychosis. A history of gastrojejunostomy, even if normal intake is possible, is a risk factor for vitamin B1 deficiency, and should be considered in the differential diagnosis of Wernicke-Korsakoff syndrome. PMID- 8365061 TI - [A case of sodium bromate intoxication with cerebral lesion]. AB - We confirmed a cerebral lesion due to sodium bromate intoxication on MRI, SPECT, auditory brainstem response (ABR) and sensory evoked potential (SEP). The patient was 34 years old, and ingested sodium bromate (14 g) to commit suicide. Vomiting, epigastralgia, watery diarrhea and anuria appeared after 30 minutes and he became deaf within 12 hours. Renal function recovered after hemodialysis. Renal biopsy revealed acute renal tubular necrosis. After one month, burning pain appeared in bilateral lower extremities. Sporadic, clear and small high intensity spots were observed in the deep white matter of the right occipitotemporal border zone and bilateral centrum semiovale on T2 and proton weighted images of brain MRI. IMP SPECT disclosed partial low perfusion in the left parietal gray matter. Central conduction time was delayed on ABR and SEP. The clinical symptoms and course together with laboratory studies suggest that the cerebral lesion was due to direct sodium bromate intoxication. PMID- 8365062 TI - [A case of pure trigeminal motor neuropathy]. AB - A 38-year-old man suffering from pure trigeminal motor neuropathy was admitted with a complaint of occipitalgia. Neurological examination showed severe wasting of the left masseter muscle on chewing. The jaw deviated to the left when he opened his mouth. Cerebrospinal fluid analysis was normal. The CT scan demonstrated a low density area in the left masseter, temporalis, lateral and medial pterygoid muscles. On MRI, the lesion of the left masseter, temporalis, lateral and medial pterygoid muscles showed high intensity of T1 and T2 weighted images. The cervical MRI revealed the non-communicating syringomyelia. Blink reflex, auditory brainstem response and trigeminal sensory evoked potentials were normal. EMG findings from the left masseter showed a neurogenic pattern. Muscle biopsy of the left temporal muscle demonstrated only fibroadipose tissue. Therefore, the present case was diagnosed as pure trigeminal motor neuropathy. It was suggested that multiple sclerosis might play an important role in the pathogenesis of this illness. PMID- 8365063 TI - [Bilateral abducens nerve palsy followed by pseudoathetosis due to pontine hemorrhage--clinical and neuroradiological study]. AB - Reported here are two cases with pontine hemorrhage presented with bilateral abducens nerve palsy and followed by pseudoathetosis, ataxia, and hemiparesis on the contralateral side of the lesion. The first case, a 57-year-old man, who suffered from bilateral abducens nerve palsy, deafness and hypoesthesia, ataxia, and hemiparesis of the right side of the body. MRI showed the confined lesion in the left side of tegmentum at the level of middle pons. When the abducens nerve palsy began to improve, pseudoathetosis of the right fingers appeared. About six months later, symptoms almost recovered, except for ataxia. The second case, a 48 year-old man who suffered from bilateral abducens nerve palsy, deafness of the left ear, and ataxia, hypoesthesia, and hemiparesis of the left side of the body was admitted. MRI disclosed a small lesion on the right side of the tegmentum at the level of middle pons. When the bilateral abducens nerve palsy was beginning to improve, pseudoathetosis of the left hand appeared. Three months later, pseudoathetosis of the left hand disappeared. Both patients presented here had a similar lesion in the tegmentum at the level of middle pons on the side contralateral to the side in which the pseudoathetosis was seen. Considering the clinical symptoms and radiological findings of these cases, it appears that a lesion which causes such rare neurological symptoms may involve the medial lemniscus, spinothalamic tract, lateral lemniscus, spinocerebellar fiber, and central tegmental tract at the tegmentum of the middle pons on the side contralateral to the cerebellar signs and pseudoathetosis. PMID- 8365064 TI - [MRI of chronic toluene intoxication]. AB - We examined MRI of 7 chronic "thinner" abusers sniffing mainly toluene for more than 5 years. MRI examination revealed cerebral atrophies in 5 out of 7 patients and hippocampal atrophies in 3 out of 7 patients. Five out of 7 patients showed low intensity signal in bilateral thalamus on T2 weighted images and 2 showed high intensity signal in internal capsule (especially posterior limb) on T2 weighted image together with the change of thalamus. The results of intelligence test for 6 patients showed significant impairment (56 +/- 17, mean +/- S.D.). SPECT with 99mTc-HMPAO of a patient showed non-selective diffuse low perfusion in cerebral cortex. Reduction of cerebral blood flow would be significant for understanding cerebral and hippocampal atrophies or the deterioration of the intelligence of chronic toluene abusers. PMID- 8365065 TI - [A case of diagnostic dyspraxia without ideomotor apraxia by callosal lesion]. AB - A case of diagnostic dyspraxia was reported. A 57-year-old right handed male had been suffering from the lack of cooperation between his right and left hands for six months. Except for decreased deep tendon reflexes in all extremities, there were no abnormal findings on neurological examination. On neuropsychological examination, he was attentive, well orientated and his spontaneous speech, comprehension, naming, repetition and reading were intact. There was peculiar dissociative behavior between his right and left hands. For instance, he put a cigarette or coin in the pocket with his right hand then his left hand took out and replaced them, and he buttoned his shirts with his right hand but then unbuttoned with his left hand. These left hand oppositional behavior to his right hand were triggered by voluntary activities of his right hand. Left unilateral agraphia was also revealed but ideomotor apraxia, compulsive manipulation of tools and grasp reflex were not demonstrated. T1-weighted MRI demonstrated irregular low signal intensity areas extending from the genu to the body of the corpus callosum. No definite lesion was detected in the medial aspect of the frontal lobe. Only small numbers of diagnostic dyspraxia have been reported and such cases without ideomotor apraxia or medial frontal lesion are even rare. MRI is very useful for detecting the lesion of the corpus callosum. PMID- 8365066 TI - [Ipsilateral gustatory disturbance by thalamic hemorrhage]. AB - Animal studies have recently demonstrated that the gustatory pathway ascends in the brainstem ipsilaterally without crossing, and terminates in the ipsilateral lower caudal limit of the thalamus, i.e., the nucleus ventralis posteromedialis parvocellularis (VPMpc). However, little is yet known about the corresponding anatomical arrangement in man. Some clinical reports on cases of ipsilateral gustatory disturbance caused by tegmental pontine hemorrhage have suggested that the human gustatory pathway may also ascend ipsilaterally in the brainstem. Our case is a 35-year-old man, who was admitted to the hospital because of double vision. Computed tomography revealed a small high density area in the right paramedian tegmentum of the upper midbrain. On the 7th hospital day, the patient suddenly complained of dysesthesia on the right side of the oral cavity. Neurological examination demonstrated remarkable total hypogeusia on the right side of the tongue. MR imaging revealed upward extension of the hematoma toward the lower caudal portion of right thalamus. This is first report to demonstrate unilateral gustatory disturbance due to lesion in the ipsilateral thalamus. It is also worth of note that unilateral gustatory disturbance caused by thalamic lesion can be accompanied by sensory impairment in the ipsilateral oral cavity. PMID- 8365067 TI - [Hemiballism-hemichorea caused by a putaminal hemorrhage with worsening after smoking--a case report]. AB - A 65-year-old hypertensive man was admitted because of abnormal involuntary movements which had an onset one month prior to the admission. Neurological examination revealed an alert and intelligent male in no acute distress. Cranial nerves appeared intact except for dysarthria. His gait was wide-based. He had hemiballism-hemichorea in his left upper and lower extremities. Cranial CT scans revealed a high density area confined to the right putamen. After admission, his involuntary movements slowly improved without medication. After near complete disappearance of his abnormal movements two weeks after admission, he noted that smoking induced choreic movement in his left side transiently. The involuntary movement ceased soon after upon stopping smoking. This was repeatedly observed not only by him but also by us. Our observation may indicate that the inhibition of the subthalamic nucleus as the result of the decrease of the putaminal output to the external segment of the globus pallidus will induce hemiballism. The effect of smoking on his involuntary movements can be understood as a result of increase in the dopamine release from the nigrostriatal terminals induced by nicotine. PMID- 8365068 TI - [A case of acute polyradiculoneuropathy following measles infection]. AB - A 39-year-old man was admitted to our hospital because of diplopia, dysphagia, tetraparesis and urinary incontinence which developed six days after fever and general cutaneous rash had appeared. On neurological examination, total ophthalmoplegia, blepharoptosis, facial nerve palsy, bulbar palsy, and tetraparesis were observed, and the deep tendon reflexes were hypoactive or absent. The cerebrospinal fluid (CSF) showed albumin-cytological dissociation. serial complement fixation tests and enzyme-linked immunosorbent assays showed an elevation of antibody titers to measles virus in sera and CSF including serum IgM antibody. On the basis of findings, we diagnosed him as acute polyradiculoneuropathy following measles infection. After 3 sessions of immunoadsorption plasmapheresis his symptoms improved promptly. Marked improvement by immunoadsorption plasmapheresis suggested that immune-mediated mechanisms were involved in the pathogenesis of acute polyradiculoneuropathy following measles infection. PMID- 8365069 TI - [A case of B-cell type acute lymphocytic leukemia presenting ophthalmoplegia]. AB - A 72-year-old man suddenly developed right blepharoptosis and diplopia and subsequently experienced motor and sensory disturbances in his upper and lower limbs. Soon he developed violet eruptions on his trunk and extremities. Approximately 2 months after the onset of his neurological symptoms, laboratory tests confirmed a diagnosis of B-cell type acute lymphocytic leukemia. The patient died 5 days later. Autopsy findings comprised prominent intrafascicular infiltration of leukemic cells in multiple peripheral nerves, including cranial and dorsal roots. However, there was no parenchymal involvement except in the dorsal root ganglia. In acute leukemia, infiltration of malignant cells in the peripheral nervous system has been reported to be uncommon compared with that in malignant lymphoma. This case of acute lymphocytic leukemia was considered to be unique with regard to the onset of neurological symptoms and autopsy findings. PMID- 8365070 TI - [A case of myasthenia gravis associated with multiple sclerosis and positive anticardiolipin antibodies]. AB - A 42-year-old housewife with myasthenia gravis (MG) for 22 years, who was initially treated by radiation to the hyperplastic thymus and anti-cholinesterase therapy, developed bilateral ptosis, paresthesia of her right face and decreased taste sensation after house work at the age of 42 years. Neurological examinations revealed lateral and vertical gaze palsy, upward nystagmus, decreased taste sensation, peripheral facial palsy on the left side. She also had hypalgesia on the right face, arm and chest up to Th7 level, and urinary retention. She had hyperreflexia on the right side but no extensor toe signs. CSF study revealed 5 cells/microliters and protein of 23 mg/dl. Serum IgG anticardiolipin antibody was positive. Magnetic resonance imaging studies revealed high intensity areas in the brainstem tegmentum and periventricular white matter. Diagnosis of multiple sclerosis (MS) was made. This is the first case in which MG, MS and serum anticardiolipin antibody were present simultaneously, which may be all due to some immunological abnormality. Steroid therapy made anti-cardiolipin antibody negative, but new MS plaque developed in 7 months, which favors diagnosis of MS rather than infarction, since the activities of ACLA were not correlating to clinical symptoms. MRI was helpful in detecting MS plaques in MG patients. PMID- 8365071 TI - [A case of flexion myelopathy presenting with reversible muscular weakness and atrophy of the unilateral proximal upper limb]. AB - A 16-year-old man visited our clinic because of right-sided weakness of shoulder abduction and elbow flexion. He was well until about three weeks previously. Neurological examination revealed only that he had severe weakness together with mild atrophy of the muscles innervated by the C5 and C6 segments (the deltoid, biceps brachii, brachioradialis), slight hypesthesia on the thumb, and loss of deep reflexes of the biceps brachii on the right. No pyramidal signs were found in the lower extremities. EMG showed neurogenic changes of the atrophied muscles. Neuroradiological studies revealed right-sided atrophy of the spinal cord at C4-5 disk level, anterior shift of the posterior cervical dura mater and congestion of the internal vertebral venous plexus mainly at C4 and C5 vertebral level with his neck flexed. Conservative physiotherapy provided a good recovery within a few months. The clinical and neuroradiological findings of this case resemble those of juvenile type of distal and segmental muscular atrophy of upper extremities excluding distribution of involved muscles because of the different level of the spinal cord lesion. Pathomechanism of this case is considered to be the same as that of juvenile type of distal and segmental muscular atrophy of upper extremities. PMID- 8365072 TI - Pediatric liver transplantation. History, recent innovations, and outlook for the future. AB - Pediatric liver transplantation has advanced remarkably over the past three decades. One-year survival has progressively increased to nearly 90% in patients transplanted for most forms of liver disease. Parallel advances in organ procurement, operative technique, immunosuppression, and infection control are responsible for improved patient survival. Among the most important advances are use of the University of Wisconsin (UW) organ preservation solution, the employment of venovenous bypass and/or "piggyback" operative technique, the development of cyclosporine A (CyA) and FK506, and the emergence of acyclovir, ganciclovir, foscarnet, and alpha interferon to combat life-threatening viral infections. The current organ shortage is being addressed by "cutdown" liver transplantation, "split liver" transplantation, and living-related donations. The next decade is likely to see advances in multi-visceral transplantation, induction of chimerism by simultaneous bone marrow-solid organ transplantation, and performance of cross-species xenografting. PMID- 8365073 TI - Financial and emotional cost of bronchopulmonary dysplasia. AB - Bronchopulmonary dysplasia (BPD) in infants with neonatal respiratory disease significantly increases the duration of hospitalization and cost of medical care. Early discharge on home oxygen therapy results in cost savings for third-party payers and the hospital, but adds financial and emotional burdens for the family. The median cost of initial hospitalization for 59 infants was $173,160 each. The median duration of home oxygen therapy was 92 days; the median cost was $5,195, compared with a projected cost of $46,920 for hospitalization for the same period. Two thirds of the 59 families experienced increased financial stress associated with marital status, reduced income, type of health insurance, and/or lack of respite or nursing help. Emotional stress was assessed in 26 (44%) of the families; one half coped well. Parents' perception of adequate insurance and stable income was significantly associated with positive coping. Providing home care for an infant with BPD on oxygen therapy is rewarding in many respects, but success requires appreciating its financial and emotional impact on families and providing them with social and financial support. PMID- 8365074 TI - Efficacy of a protocol to distinguish risk of serious bacterial infection in the outpatient evaluation of febrile young infants. AB - A study of 534 febrile infants ages 4 to 8 weeks evaluated for sepsis assessed the efficacy of the Milwaukee Protocol (MP) for selecting patients at low risk for serious bacterial infection (SBI) who might benefit from outpatient management. Two groups were compared: 1) Infants with uncompromised presentation (UP) who met all MP criteria received ceftriaxone 50 mg/kg and were discharged, then reevaluated within 24 hours. 2) Infants with compromised presentation (CP) who did not meet MP criteria were hospitalized for antibiotic therapy pending culture results. Of 391 CP patients, 23 (5.9%) had SBI; of 143 UP patients, 1 (0.7%) had SBI (P < .02). The MP criteria had a sensitivity of 96% and a 99% negative predictive value for distinguishing SBI outcome. The only UP patient with SBI was afebrile and had a negative repeat blood culture after 24 hours, and recovered with no complications. Managing UP infants as outpatients avoided 48 to 72 hours of hospitalization, decreasing health-care costs by an estimated total of $465,170. PMID- 8365075 TI - Catch-up head growth and motor performance in very-low-birthweight infants. AB - The relationship between catch-up head growth and motor performance was examined in 48 very-low-birthweight (< 1,500 g) infants. All infants were nonasphyxiated, normocephalic, and appropriately grown for gestational age at birth. Serial cranial ultrasonography during the first month of life revealed no intracranial pathology. The age of catch-up head growth, defined as the corrected age when the head circumference recovered to the 5th percentile, was determined for each infant. At 12 months corrected age, the infants were evaluated and grouped according to normal (n = 37) or abnormal (n = 11) motor assessments. The abnormal group achieved catch-up head growth by 7.7 +/- 2.1 months vs 3.7 +/- 3.1 months for the normal group (P < .05). Only 27% of the motor-delayed infants achieved catch-up head growth by 6 months corrected age, as compared with 89% of the normal infants (P < .05). Premature infants who have achieved catch-up head growth by 6 months corrected age, corresponding to the period of maximal postnatal brain growth, have fewer motor abnormalities than infants who attain catch-up head growth later. There is a significant relationship between head circumference at 6 months corrected age and motor development in very-low birthweight infants. PMID- 8365076 TI - Comparison of self-referred and physician-referred patients to a pediatric diagnostic center. AB - Self-referral of children by parents without the knowledge of the child's regular physician can lead to redundant or unnecessary testing and difficulty in arranging follow-up care. This study was designed to investigate reasons for self referral in a hospital-based pediatric diagnostic center. During the study period, 59 patients were referred by their regular physicians and 51 were self referred. In multiple-choice questionnaires completed by 85% of the parents, nearly half (18/39; 46%) of those who were self-referred but only 2/51 (4%) of physician-referred parents said the child's regular physician was unconcerned about the medical problem. Further study on the causes for this perception is needed before recommendations can be made to physicians about demonstrating their concern to families. PMID- 8365077 TI - Treatment variables and intellectual outcome in children with classic phenylketonuria. A single-center-based study. AB - Records of 46 patients with classic phenylketonuria (PKU) were used to determine treatment variables associated with intellectual outcome. Patients comprised three groups: phenylalanine-restricted diet started 1) after 3 months and loss of diet control at a mean age of 7 years, 2) before age 3 months and loss of diet control at a mean age of 5 years, and 3) before age 3 months and through a mean age of 11 years. All underwent IQ testing during the diet; groups 1 and 2 were retested at a mean of six years off the diet. On the diet, groups 2 and 3 had higher IQs than group 1; group 3 IQ was also higher than IQ off diet in groups 1 and 2. After discontinuing the diet, group 2 IQs decreased significantly. Predictors of IQ in group 1 were age at loss of diet control and percentage of phenylalanine concentrations > 15 mg/dL; in group 2, mean phenylalanine concentrations and age at loss of diet control. Predictors of changes in group 1 IQs were global degree of dietary control and percentage of phenylalanine concentrations > 15 mg/dL; in group 2, phenylalanine concentrations of < 3 mg/dL and age at start of diet. Group 1 patients with phenylalanine concentrations < 3 mg/dL or > 15 mg/dL achieved no IQ gain by continuing the diet after age 7 years. Thus, intellectual prognosis is best for PKU patients who start a phenylalanine restricted diet early and continue through age 12 years. PMID- 8365078 TI - Evolution of height and bone age in primary congenital hypothyroidism. AB - Thyroid hormones are fundamental for growth and bone maturity. Retarded physical and osseous development signals congenital hypothyroidism. This study assessed the evolution of height and bone age and final height after hormone replacement treatment in 25 patients with primary congenital hypothyroidism. Bone ages, measured periodically for 12 years after treatment began, were expressed as standard deviation scores (SDS) corresponding to chronologic age. Heights were expressed as SDS and related to standardized curves and genetic height. All patients experienced height recovery during the first year. Of 19 patients who reached their final height, 16 surpassed the expected mean for genetic height. Bone age accelerated progressively, with total recovery toward the third year, and remained accelerated, reaching +1.43 +/- 1.27 in relation to chronologic age 12 years after hormone replacement began. Thus, early diagnosis and adequate treatment of congenital hypothyroidism improved growth and osseous development, although progressive acceleration of bone age may have limited final height in some children. PMID- 8365079 TI - A comparative evaluation of whey hydrolysate and whey-predominant formulas. How well do infants accept and tolerate them? AB - Whey hydrolysate formulas are a recent and important innovation in infant feeding. This study compared clinical tolerance and acceptability of a whey hydrolysate formula (WH) with those of a whey-predominant formula (WF) in 45 infants. Four infants (16%) who refused to drink WH formula were eliminated from the study. Mean volume intake was significantly lower for WH (120 mL/kg/day) than for WF (147 mL/kg/day; P < .001). Consequently, mean caloric intake was also significantly different: 80 kcal/kg/day (WF) vs 97 kcal/kg/day (WF; P < .001). Nevertheless, weight gain from birth to 13 weeks of age was nearly identical in both groups (171% for WH vs 178% for WF). No significant differences were noted in duration of feeding, number of pauses during feeding, number of stools per day, or number of regurgitations per day. The lower rate of caloric intake and the dropout rate of 16% for WH raise questions about the use of WH formula in normal infants, as has become the case in some Western European regions. PMID- 8365080 TI - An unusual case of relapsing myositis in a 12-year-old child. PMID- 8365081 TI - Hepatitis B. A disease needing a vaccine or a vaccine needing a disease? PMID- 8365082 TI - Footwear and orthoses for diabetic patients. PMID- 8365083 TI - Complications of diabetes in childhood. PMID- 8365084 TI - Recurrent severe hypoglycaemia and cognitive function in type 1 diabetes. PMID- 8365085 TI - Diet treatment of newly presenting type 2 diabetes improves insulin secretory capacity, but has no effect on insulin sensitivity. AB - Fifteen newly diagnosed obese Type 2 diabetic subjects were treated with diet alone for 3 months with a median 1.5 kg weight loss. Each had a Continuous Infusion of Glucose with Model Assessment (CIGMA) test, at diagnosis and at 3 months, measuring insulin and C-peptide responses, and deriving mathematically modelled measures of beta-cell function and insulin sensitivity. Median fasting glucoses were 9.6 mmol l-1 at diagnosis and 8.5 mmol l-1 at 3 months (NS). Median fasting insulin was 9.3 mU l-1 at diagnosis and 11.7 mU l-1 at 3 months (NS). Median fasting C-peptide was 0.58 nmol l-1 at diagnosis and 0.64 nmol l-1 at 3 months (p < 0.05). Median achieved plasma insulin increased from 13.8 mU l-1 at diagnosis to 17 mU l-1 at 3 months (p < 0.02); median achieved plasma C-peptide increased from 0.72 nmol l-1 at diagnosis to 0.81 nmol l-1 at 3 months (p < 0.002). Modelled beta-cell function rose from median 26% at diagnosis to 37% at 3 months (p < 0.02). Modelled insulin sensitivity showed no significant change (median 0.31 at diagnosis, 0.27 at 3 months, NS). Elevation of achieved C-peptide was positively correlated with weight loss (Rs = 0.53, p < 0.05), but not with change in fasting glucose. Diet treatment of newly diagnosed Type 2 diabetes, with modest weight loss, results primarily in improvement of insulin secretory capacity, rather than insulin sensitivity. PMID- 8365086 TI - The degree of day-to-day variation in food intake in diabetic patients. AB - A prospective study of food intake using 7 day food diaries was undertaken in 92 diabetic men and women aged 17-81 years. The median individual day-to-day coefficients of variation for energy intake were: in insulin treated patients 12.0%, in non-insulin treated patients 13.7%; for carbohydrate intake 14.5% and 13.8% and for fat 20.7% and 20.8%, respectively. The median individual differences between the minimum and maximum daily intake of energy in insulin treated patients was 787 kcal, in non-insulin treated patients 649 kcal, for carbohydrate intake 89g and 77g and fat 50g and 43g, respectively. Only 39% patients ate within 20% of their prescribed carbohydrate diet. In non-insulin treated patients on prescribed calorie controlled diets, calorie consumption was on average 46% in excess of that prescribed. Although the variation in dietary intake in diabetic patients is large, it is smaller than that reported in non diabetic subjects in the UK. This variation is likely to make the manipulation of other antidiabetic therapy both difficult and somewhat arbitrary. PMID- 8365087 TI - Glucose profiles in children two years after the onset of type 1 diabetes. AB - The relationship of 24-h glucose profiles to age, haemoglobin A1c (HbA1c), and C peptide concentration was analysed in consecutive, unselected children who had developed Type 1 diabetes 2 years earlier. Seventy-seven children in four age groups (age 2-4 years, n = 9; 5-8 years, n = 14; 9-12 years, n = 26; and 13-17 years, n = 28) were studied. Each child was hospitalized for 2 days for the investigations. Mean blood glucose concentration was 9.7 +/- 4.1 (SD) mmol l-1 in children aged 2-4 years; 10.7 +/- 4.0 mmol l-1 in those aged 5-8 years; 11.3 +/- 3.4 mmol l-1 in those aged 9-12 years; and 9.8 +/- 3.3 mmol l-1 in those aged 13 17 years. Results were > 7.0 mmol l-1 in 69% (range 56-76%) and > 10 mmol l-1 in 49% (39-57%) of the measurements. Values decreased by 30% (21-43%) between 10 pm and 3 am. The nadir of the mean profiles of the groups was always at 3 am. Glucose concentration was mmol l-1 in 25% (14-50%), < 2.5 mmol l-1 in 9.6% (0 21%), and < 2.0 mmol l-1 in 2.7% (0-4.2%) of the children at 3 am; hypoglycaemia was most common in those aged 5-8 years. Of the four profile characteristics used, mean blood glucose predicted HbA1c (R2 = 24.7%, p < 0.00005, multiple linear regression analysis), and slightly more in combination with age (R2 = 32.0%, p < 0.00005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365088 TI - Psychological factors and their relationship to diabetes control. AB - Thirty-nine Type 1 diabetic patients were asked to complete an Eysenck Personality Questionnaire (EPQ). A significant relationship was found between neuroticism scores and glycosylated haemoglobin concentrations (r = 0.43, p < 0.01) and also fructosamine (r = 0.45, p < 0.01). Patients with glycosylated haemoglobin concentrations greater than or equal to 10 (n = 13) had significantly higher neuroticism scores than patients with glycosylated haemoglobin results less than or equal to 8 (n = 11) (p < 0.01). PMID- 8365089 TI - Action profile of the rapid acting insulin analogue: human insulin B28Asp. AB - The time-action profile of the human insulin analogue B28Asp, which displays faster absorption rates from subcutaneous tissue compared to soluble human insulin, was studied under euglycaemic glucose clamp conditions (blood glucose 5.0 mmol l-1) in 14 healthy male volunteers. Subcutaneous injection of 0.15 U kg 1 body weight (range 9.5-14.3 U) of the insulin analogue or soluble human insulin resulted in half-maximal glucose infusion rates (after subtraction of mean baseline glucose infusion rates) that were reached significantly earlier after injection of B28Asp (45 +/- 11 (SD) min) as compared to human insulin (58 +/- 25 min, p < 0.05). Forty-five and 60 min after injection of human insulin, glucose infusion rates had increased by 3.4 +/- 1.8 and 4.8 +/- 2.3 mg min-1 kg-1 above baseline glucose infusion rates, reflecting 30 +/- 15 and 42 +/- 17% of maximal action of 10.6 +/- 2.7 mg min-1 kg-1. Following the injection of B28Asp, glucose infusion rates increased by 6.3 +/- 2.7 after 45 min and by 7.9 +/- 2.8 mg min-1 kg-1 after 60 min above baseline glucose infusion rates, reflecting 64 +/- 28% and 81 +/- 26% of maximal action of human soluble insulin (p < 0.001). Peak glucose infusion rates after injection of B28Asp were significantly higher and were reached earlier than after subcutaneous injection of soluble human insulin (p < 0.05 and p < 0.001). The human insulin analogue B28Asp showed a significantly faster onset of action as compared to soluble human insulin. PMID- 8365090 TI - Pregnancy is not a risk factor for a deterioration of autonomic nervous function in diabetic women. AB - Pregnancy may have an untoward effect on diabetic retinopathy and nephropathy and symptoms of autonomic neuropathy may also be exacerbated during pregnancy. To test the hypothesis that previous pregnancies during the diabetic state are associated with increased risk of development of autonomic dysfunction, autonomic nervous function and pregnancy history were assessed in 117 women with long standing Type 1 diabetes mellitus. Thirty-eight women (32%) had autonomic dysfunction, defined as at least one abnormal cardiovascular test. The presence of autonomic dysfunction was not related to the number of pregnancies during the disease state. Thus, this cross-sectional study suggests that pregnancies do not represent a risk factor for a deterioration of autonomic nervous function and development of autonomic neuropathy in diabetic women. PMID- 8365091 TI - A prospective study of clinical and metabolic associates of proteinuria in patients with type 2 diabetes mellitus. AB - Urinary protein excretion rate and clinical and metabolic associates were investigated in a group of 108 patients with Type 2 diabetes mellitus at the time of diagnosis and after 5 years, and also 121 control subjects. The presence of coronary heart disease, neuropathy and retinopathy, cardiovascular risk factors and 24-h urinary excretion rate of albumin, beta-2-microglobulin, and IgG were examined. At the 5-year examination, urinary excretion rate of albumin was higher in diabetic patients than in control subjects (39 +/- 75 vs 16 +/- 28 mg 24 h-1 for men, p < 0.05; 38 +/- 57 vs 22 +/- 42 mg 24(-1) h for women, p < 0.01). Furthermore, increased beta-2-microglobulin excretion rate, a marker of tubular impairment, was observed in diabetic men as compared to control men (0.17 +/- 0.15 vs 0.14 +/- 0.21 mg 24 h-1, p < 0.05). Diabetic patients with increased albumin excretion rate (> 30 mg 24 h-1) showed poorer metabolic control than those with normal albumin excretion rate, but no significant differences in body mass index or in the frequencies of smoking, hypertension, coronary heart disease or retinopathy and neuropathy were observed between the groups. Baseline hyperinsulinaemia was closely associated with increasing albuminuria at the 5 year examination. PMID- 8365092 TI - Bacteriuria, bacterial virulence and host factors in diabetic patients. AB - The prevalence of bacteriuria as well as bacterial virulence and host factors were studied in 514 diabetic outpatients and 405 nondiabetic controls. The prevalence of bacteriuria was not significantly higher in diabetic women (15/239, 6.3%) than in age-matched nondiabetic women (8/236, 3.4%). In diabetic and nondiabetic men, the prevalence was also similar but lower than in women. E. coli was found in 55% of urine cultures with significant growth from diabetic patients, while in 91% of positive cultures from nondiabetic controls. Most E. coli strains lacked ability of P-fimbriae-mediated adhesion and aerobactin mediated iron uptake, indicating low bacterial virulence. Long-term metabolic control (HbA1c), prevalence of retinopathy, neuropathy and previous foot ulcers were similar in bacteriuric and nonbacteriuric diabetic patients, matched according to gender, age, and duration of diabetes. Renal function was also similar, though the frequency of proteinuria and elevated blood pressure tended to be higher in the bacteriuric than in the noninfected group. Eight-three percent of the bacteriuric patients reported previous urinary tract infections but only 61% of nonbacteriuric patients (p = 0.07). As compared to non-diabetic women, diabetic women reported significantly more previous urinary tract infections (p < 0.01). In conclusion, the prevalence of bacteriuria in diabetic outpatients was not significantly higher than in non-diabetic outpatients or healthy volunteers. No studied host factor was clearly associated with bacteriuria in diabetic patients, although proteinuria and hypertension tended to be more common. The infecting E. coli strains were of low virulence. PMID- 8365093 TI - The five-year incidence of blindness after introducing a screening programme for early detection of treatable diabetic retinopathy. AB - The incidence of moderate visual impairment and blindness due to diabetic retinopathy was studied 5 years after introducing a screening system for early detection of treatable retinopathy. Photocoagulation was performed in patients with clinically significant macular oedema, severe preproliferative, and proliferative retinopathy. Eighty-eight percent of 470 Type 1 and 88% of 388 Type 2 diabetic patients were still available for follow-up. In the Type 1 group, the five-year incidence of blindness and moderate visual impairment were 0.5% and 1.2%, respectively. Corresponding figures for the Type 2 diabetic patients were 0.6% and 1.7%, respectively. The majority of patients with loss of vision had severe retinopathy at baseline. Among those who entered the screening programme with no or mild retinopathy, loss of vision occurred in only one of the Type 1 and four of the Type 2 diabetic patients. It is concluded that the risk for visual impairment and blindness due to diabetes can be substantially reduced by using programmes for early detection of and effective treatment of diabetic retinopathy. PMID- 8365094 TI - Accurate and precise blood glucose measurement in the hypoglycaemic range. AB - The aim of the study was to evaluate the performance of an electrochemical blood glucose sensor, the satellite G, in the low-normal and hypoglycaemic range. Eighty-five venous blood samples with glucose concentrations below 4.0 mmol I-1 from six patients with Type 1 diabetes undergoing induced hypoglycaemia were measured in duplicate on the sensor and a reference method, the Yellow Springs whole blood glucose analyser. The sensor values correlated well with the reference method (r = 0.9, p < 0.001) with a mean absolute percentage bias of 10.7%. The 95% confidence limits of agreement between methods were +0.7 and -0.6 mmol I-1 with a mean difference of 0.004 mmol I-1. More than 80% of the sensor measurements were within 20%, and 60% were within 10% of the reference method. Measured over all samples, the sensor had a coefficient of variation of 7.2% for paired measurements. The coefficients of variation of 20 measurements on each of two samples with glucose concentrations of 1.3 and 2.6 mmol I-1 were 9.1% and 5.8%, respectively. We conclude that the satellite G measures blood glucose accurately and precisely in the low range. PMID- 8365095 TI - Glycated haemoglobin centiles: a basis for audit in children's clinics? AB - Services for children with diabetes are a good model for audit because of relatively well-defined and available measures of outcome. Estimation of glycated haemoglobin (HbA1) is accepted as one index of control, although the assay and normal ranges vary in different centres. Sheffield has a stable clinic population and we have taken blood for HbA1 on each patient two to four times per year since 1983. HbA1 values have been aligned in 3-monthly increments from time of diagnosis to construct a graph showing the mean plus or minus two standard deviation values for the clinic population and also a rough 'centile chart' that describes the unfortunate but expected pattern of deteriorating control with duration of diabetes. There are undoubtedly methodological flaws in this novel approach; however, such charts constructed for each clinic may be a suitable basis for comparative assessment of the control of an individual and also for auditing the effects of changes in practice that strive for optimum glucose levels in the clinic population. PMID- 8365096 TI - An approach to the use of the DO IT Study Group guidelines for supporting the optimal implementation of information systems in diabetes care. AB - The usefulness of the 1992 DO IT Study Group guidelines for diabetes data information systems was assessed using two established diabetes databases designed for different purposes. The recommendations detailed in the guidelines, written in four separate but overlapping modules, were applied individually to each database in turn. Percentage compliance with the recommendation to collect the DIABCARE dataset was high, after discounting specialist areas. While on the whole the information systems complied with the guidelines within the purposes for which they were designed, areas highlighted as demanding further action in at least one of the two systems included password protection, data validation checks, screen design, and communication with those whose records were held on the systems. Application of the guidelines is already stimulating attention to some of these areas. Some of the guidelines proved rather vague in construction to be applied in any formal sense, while others (for example in relation to international accreditation of datasets) were not applicable to individual systems. The results suggest the importance of a structured approach to the design, development, and ongoing assessment of information systems in diabetes, but require the present guidelines to develop a more formal structure to be fully effective. The widespread adoption and further testing and refinement of these guidelines (both within and outside Europe) should promote the ultimate goal of improved diabetes care. PMID- 8365097 TI - Emphysematous pyelonephritis: a case report and review of the literature. AB - Emphysematous pyelonephritis is a rare and life-threatening suppurative infection of renal parenchymal and perirenal tissues, characterized by spontaneous gas production. Although uncommon (76 cases in the literature), it occurs almost exclusively in diabetic patients (87% of the cases). We describe a recent case of a diabetic woman with emphysematous pyelonephritis due to E. coli, successfully managed with unilateral nephrectomy. Symptoms, diagnostic approach and management are discussed and related to the previously reported series. PMID- 8365098 TI - Awareness of hypoglycaemia--problems and perspectives, London, December 1992. PMID- 8365099 TI - Severe lipoatrophy with human insulin: successfully treated by CSII. PMID- 8365100 TI - Shared antigenic determinants of immunoglobulins in phylogeny and in comparison with T-cell receptors. AB - 1. Immunoglobulins are a complex multigene family of proteins specified by genes encoding variable (V), sometimes diversity (D), joining (J), and constant (C) domains. 2. Cross-reactions involving conformational determinants related to the VHa system of rabbits occur on heavy chains of vertebrate species ranging from elasmobranchs to man. 3. Serological markers characteristic of mu chains, the heavy chain of the IgM macroglobulins, occur on homologous heavy chains of species representing all vertebrate classes. 4. Serological markers characteristic of gamma type heavy chains, the major isotype in man, are restricted to the mammals, but are found on representatives of even the most primitive mammals, the egg-laying monotremes. 5. Variable region markers characteristic of lambda light chains are shared by light chains of shark and man. 6. Certain idiotypic markers defined by combining site V region sequences are broadly distributed in evolution. 7. Use of synthetic peptides as antigens and in epitope mapping show that amino acid sequences from the third framework region of the variable domain are broadly shared among light chain in phylogeny and between light chains and T-cell receptor beta chains. 8. The "switch peptides" linking the V and C domains of light chains and T-cell receptors, specified by the C-terminal portion of the J segment and the N-terminus of the constant region, are exposed in the three-dimensional structure of immunoglobulin or Tcrs, show striking homology, and form broadly shared antigenic determinants characteristic of immunoglobulins. 9. Although the multigene nature of the immunoglobulins and the complexity of antigenic determinants expressed by these large proteins renders comparison among molecules difficult, serum immunoglobulins and the closely related T-cell receptors express numerous shared determinants defined on the basis of amino acid sequence homology and three dimensional conformations. PMID- 8365101 TI - Protein protease inhibitors in insects and comparison with mammalian inhibitors. AB - 1. Studies on insect protein protease inhibitors are summarized. Biochemical, genetic and physiological investigations of the silkworm are performed. 2. In addition, the properties and characteristics of fungal protease inhibitors from the silkworm (Bombyx mori) are described and their importance as defensive functions is emphasized. 3. This review also concerns comparative and evolutionary studies of protease inhibitors from various sources. 4. The biological significance of inhibitors is discussed in view of the extensive experimental results. PMID- 8365102 TI - The calf thymus superoxide dismutase: a protein active on cholesterol metabolism. AB - 1. Recent studies on the new aspects of thymus physiology describing the correlation between thymus hormones and pituitary hormone secretion, are illustrated. 2. Subsequently, results of a series of experiments showing the effect of a calf thymus protein on cholesterol synthesis in rat hepatocyte cells are discussed. 3. The last part of this review is focused on the biochemical characteristics of this calf thymus protein that revealed an amino acid sequence that was found to be identical with regions of bovine erythrocyte superoxide dismutase. New perspectives of studies, focused on the isolation of possible superoxide dismutase membrane receptors, are described at the end of this review. PMID- 8365103 TI - Biosynthesis of frog skin mucins: cysteine-rich shuffled modules, polydispersities and genetic polymorphism. AB - 1. Frog integumentary mucins (FIM-A.1, FIM-B.1 and FIM-C.1) consist of typical threonine-rich highly O-glycosylated (semi)repetitive domains, and cysteine-rich modules, i.e. the P-domain, the short consensus repeat and a region with high similarity to the C-terminal end of von Willebrand factor (designated here CC29 motif). 2. These modules are thought to be involved in protein-protein interactions and they have been observed in a variety of extracellular proteins. In FIMs, these modules may be involved in oligomerization processes leading to an entangled mucin network. 3. Polydispersities have been detected in FIM-B.1 and FIM-C.1 within single individuals. Multiple transcripts are probably generated by alternative splicing of a huge array of different (semi)repetitive cassettes encoding the threonine-rich domains. 4. Furthermore, genetic polymorphism is observed between different individuals, probably due to allelic variations in the number of (semi)repetitive cassettes. PMID- 8365104 TI - Comparative analysis of macromolecules in mollusc shells. AB - 1. Proteins and polysaccharides were isolated from the shells of molluscs; blue mussel, Mytilus edulis, chambered nautilus, Nautilus pompilius, and red abalone, Haliotus rufescens. 2. N-acetyl glucosamine was detected in nautilus but not mussel or abalone. 3. Amino acid analysis of protein fractions was completed for the three molluscs and purified proteins from the mussel were partially sequenced. 4. Calcium binding studies were carried out with some of the protein fractions. PMID- 8365105 TI - A comparative study on liver ornithine carbamoyl transferase from a marine mammal Stenella and an elasmobranch Sphyrna zygaena. AB - 1. Ornithine carbamoyl transferases from liver of the dolphin Stenella and the shark Sphyrna zygaena were purified to homogenity and compared for some kinetic and structural properties. 2. The two enzymes showed a specific activity of 211 and 115 respectively. 3. With respect to molecular weight, trimeric subunit structure and Km values, they were alike and similar to enzymes from other species. 4. Both enzymes were thermolable, but they were protected from thermal inactivation in a different way by ornithine and phosphate. 5. The two enzymes focused, respectively, at pH 8.6 and between pH 6.4 and 8.0, the former value being appreciably higher than those of enzymes from other species. PMID- 8365106 TI - Comparative oxidative rates of methionine hydroxy analogue in rat and chicken kidney. AB - 1. L-2-HAOX A and L-2-HAOX B were purified from chicken and rat kidney with purification factors of 550 and 45, respectively. 2. It was established that both enzymes were tetrameric (M(r) = 169,000) and consisted of 40 kDa monomers. 3. While chicken kidney L-2-HAOX A is N-terminally blocked like spinach glycolate oxidase and chicken liver L-2-HAOX A, L-2-HOAX B begins with a Pro residue. 4. The kinetic parameters of L-HMB oxidation by L-2-HAOX A and B were determined. 5. The results are particularly interesting as regards L-HMB oxidation by L-2-HAOX B. PMID- 8365107 TI - Metabolic alterations in organs of Meriones unguiculatus infected with Echinococcus multilocularis. AB - 1. 1H-NMR spectra of liver, spleen and kidney extracts from Meriones unguiculatus infected with Echinococcus multilocularis showed decreased levels of glucose. In addition, the liver extracts were severely glycogen-depleted. 2. Both livers and spleens contained less glycine, taurine and acetate. Spleens also had fewer cholines and less lactate but more betaine and alanine. 3. In the kidneys, elevated concentrations of succinate, acetate and lactate were found. PMID- 8365108 TI - Rodent tissue alpha-L-fucosidases: analysis of brain and spleen isoforms and characterization of the purified hamster liver enzyme. AB - 1. Isoelectric focusing of brain and spleen alpha-L-fucosidases from four rodents (rat, mouse, guinea-pig, hamster) indicated that only mouse and hamster tissues contained isoforms with significant amounts of activity above pI 7.0. 2. Hamster liver alpha-L-fucosidase was purified approximately 57,000-fold in 80% yield (to a final specific activity of 24,700 nmol/min/mg protein) by affinity chromatography on agarose-epsilon-aminocaproyl-fucosamine. 3. SDS-PAGE analysis of hamster liver alpha-L-fucosidase indicated the presence of one to two closely spaced subunits at 56 and 60 kDa. Western blotting analysis indicated the hamster enzyme was recognized by polyclonal antibodies but not by a monoclonal antibody (both antibodies prepared against human liver alpha-L-fucosidase). 4. The pH activity curve of hamster liver alpha-L-fucosidase is broad with an optimum centered around pH 6.8 and with high activity between pH 5.5 and 7.5. PMID- 8365109 TI - Functional and structural identification of a new lectin activity of Borrelia recurrentis spirochetes. AB - 1. Haemagglutinating activity (HA) was found and characterized in lysate of the spirochete Borrelia recurrentis. 2. The highest HA was observed using native rabbit red blood cells (RBC), especially oxidized rabbit RBC. 3. In a haemagglutination inhibition test the HA showed an affinity with monosaccharides D-glucosamine, D-galactosamine and N-acetyl-D-mannosamine and several glycoproteins and polysaccharides. 4. An inhibitory effect was also achieved by mouse monoclonal antibody H 9724, polyclonal antibodies from B. recurrentis infected mice and with rabbit polyclonal antibodies directed against B. recurrentis HA. 5. B. recurrentis proteins components of 29, 33, 41 and 55 kDa were identified by immunoblotting as structural subunits of complex binding activity of a new agglutinin. PMID- 8365110 TI - Fatty acid composition of fats around the mystacial and superciliary vibrissae differs from that of blubber in the Saimaa ringed seal (Phoca hispida saimensis). AB - 1. Adipose tissues associated with the mystacial and superciliary vibrissae of the Saimaa seal (Phoca hispida saimensis) contained 31% of hexadecenoic acid (16:1 omega 7), which was almost twice the already high amount in blubber. The amount of tetradecenoic acid (14:1 omega 5) was also double that in blubber. 2. At the same time the levels of long-chain highly unsaturated docosapentaenoic (22:5 omega 3) and docosahexaenoic acids (22:6 omega 3) were only two-thirds of those found in blubber. 3. It is suggested that the excess of low-melting monoenoic fatty acids (14:1 and 16:1) in adipose tissues near the vibrissae might not be compensation for the low supply of dietary polyunsaturated fatty acids in these tissues, but that the self-induced excess of monoenoic fatty acids ensured the proper functioning of these well-developed sense organs. PMID- 8365111 TI - Fatty acid composition in liver and blubber of the Saimaa ringed seal (Phoca hispida saimensis) compared with that of the ringed seal (Phoca hispida botnica) and grey seal (Halichoerus grypus from the Baltic. AB - 1. The main differences in fatty acid composition of blubber between the Saimaa seal (Phoca hispida saimensis) and the Baltic seals (Phoca hispida botnica and Halichoerus grypus) were, that in fresh water the proportions of polyunsaturated C18 acids and arachidonic acid (20:4 omega 6) were high. 2. The trend became more evident when data on ringed seals from northern oceans were compared with the present data. 3. The proportions of exogenous 20:1 and 22:1 were extremely low in ringed seals from Lake Saimaa and in Baltic seals compared with seals living in oceans. PMID- 8365112 TI - Butyrylcholinesterase from intestinal epithelial cells of quail, chick and duck: a comparative study during development. AB - 1. Epithelial cells of avian intestine express non-specific cholinesterase (butyrylcholinesterase, BuChE) activity both in the embryo and adult animal. 2. Quail, duck and chick exhibit increased BuChE activity during the late embryonic period followed by decreased activity. The minimum value is reached after hatching at day 1 in quail, day 4 in chick and day 6 in duck. 3. The three species display marked sex-related differences mainly during the peri-hatching period. BuChE activity is higher in females than in males. 4. The three globular forms, G1, G2 and G4, are detected during the last days of embryonic development. After hatching, changes in the relative amounts of these forms are related to the disappearance of G2 and the gradual decrease of G4. In adult quail and duck, G4 is not detected and BuChE activity corresponds only to the G1 form. 5. The changes in BuChE activity and distribution of the molecular forms occur in a similar manner in all three species although the embryonic periods differ notably, suggesting that hormonal factors secreted during this period and involved in the preparation of hatching may regulate BuChE activity. PMID- 8365113 TI - Electrospray mass spectrometric analysis of river buffalo (Bubalus bubalis) hemoglobins. Re-examination of alpha 1 and alpha 3 globin chain sequences. AB - 1. The accurate molecular weight of the globin chains from river buffalo hemoglobin components has been determined by means of electrospray mass spectrometry. 2. The ES/MS analysis demonstrated that all the buffalo Hb components share a common beta chain whose mass value coincides with that expected on the basis of the reported sequence. 3. The AA phenotype alpha 1 and alpha 3 globin chains exhibited a 30 Da mass difference as compared to their predicted molecular weights. Careful re-examination of the two alpha globin sequences by FAB/MS revealed the occurrence of sequence errors and hence the correct primary structure of both alpha chains was established. PMID- 8365114 TI - Enzyme properties of monoamine oxidase in the frontal cortex and liver of the gerbil (Meriones unguiculatus). AB - 1. Enzyme properties of monoamine oxidase (MAO) in the frontal cortex and liver of the gerbil were investigated using 5-hydroxytryptamine (5-HT), benzylamine (Bz) and tyramine (Tyr) as substrates. 2. The Km values of MAO towards the three substrates were almost similar to the values in other species. The Vmax value of MAO towards Bz was much lower than the value towards 5-HT. 3. In the inhibition studies with selective MAO-A and MAO-B inhibitors, clorgyline and deprenyl, deamination of 5-HT, Bz and Tyr in both tissues was induced by MAO-A alone, MAO-B alone and both forms of the enzyme, respectively, indicating the same substrate specificity as that in rats. 4. The apparent proportion of MAO-A to MAO-B activities in the gerbil liver was approximately 6:4, whereas MAO-A in the frontal cortex of the gerbil was exclusively predominant, consistent with the previous data in the golden hamster which belongs to the same family as the gerbil. PMID- 8365115 TI - Clinical biochemical reference ranges for female alpacas (Lama pacos). AB - 1. Serum samples were collected from 352 healthy female alpacas and tested for 17 clinical biochemical analytes. 2. From the total population of alpacas tested, 205 were pregnant, 68 were not pregnant and 79 had an unknown pregnancy status. 3. Reference ranges for the female alpacas were determined for all the biochemical analytes, and compared to ranges reported for llamas, cattle, sheep and goats. 4. The mean values for pregnant and non-pregnant females were compared and any statistically significant differences identified. 5. The biochemical values reported here are suitable as reference ranges for pregnant and non pregnant female alpacas. PMID- 8365116 TI - Comparative studies of effects of dehydroepiandrosterone on rat and chicken liver. AB - 1. An attempt to identify the cause of decrease of gain in body weight during dehydroepiandrosterone (DHEA) treatment was made comparing the effects of hormone treatment on chickens and rats. 2. Chickens treated with DHEA for 7-10 days do not change their weight gain with respect to controls although their mitochondrial respiration and peroxisomal catalase (index of peroxisomal mass) were increased. 3. Liver cytosolic malic enzyme and sn-glycerol-3-phosphate dehydrogenase were depressed in chickens treated with DHEA in comparison with activities in untreated controls. DHEA treatment did not increase the activity of mitochondrial sn-glycerol 3-phosphate dehydrogenase. 4. In contrast to rat liver cytosolic sn-glycerol-3-phosphate dehydrogenase this enzyme in chicken liver was inactive with NADPH. PMID- 8365117 TI - Fecal bile acids and neutral sterols in the cotton-top tamarin (Saguinus oedipus). AB - 1. The cotton-top tamarin (Saguinus oedipus), a small New World primate susceptible to spontaneous development of colon cancer, was studied for its fecal neutral sterol and bile salt composition. 2. Standardization procedures to establish the effect of exposure of the stool to room temperature air for various time-periods showed no significant effects on the neutral sterol and bile salt composition of the samples. 3. Microbial degradation of cholesterol and bile acids to secondary metabolites showed a progressive rise during the first year of life after which some degree of homeostasis was observed. 4. The proportion of cholesterol that remained unmetabolized by colonic microflora was in excess of 50%, an amount that was significantly higher than in man and other higher primates. 5. Ursodeoxycholic acid was identified as a significant (12%) component of fecal bile acids in this species. 6. Secondary bile acids formed by the action of enteric microflora were also significantly lower than levels found in man and other animals. PMID- 8365118 TI - Isolation and characterization of cock brain coated vesicles in comparison with porcine brain coated vesicles. AB - 1. Cock brain coated vesicles (CBCVs) were isolated and compared with porcine brain coated vesicles (PBCVs). 2. The fine structure of CBCVs was quite similar to that of PBCVs. 3. Size distribution of CBCVs showed a rather single population, whereas that of PBCVs seemed to consist at least two subpopulations. 4. CBCVs possessed proteins quite characteristic of coated vesicles (CVs). 5. The protein composition of CBCVs was very like that of PBCVs with the exception of clathrin light chain b. 6. A small difference in the electrophoretic mobility existed between CBCVs and PBCVs. 7. The density of CBCVs was slightly greater than that of PBCVs. PMID- 8365119 TI - The role of subfractions of high density lipoprotein in the in vivo transport of cholesterol from cholesterol-loaded hepatic and peripheral endothelial cells in the New Zealand white rabbit. AB - 1. High density lipoprotein (HDL) of the New Zealand White rabbit was separated by heparin-Sepharose affinity chromatography into six distinct subfractions of different composition and particle size. 2. When human acetyl LDL containing [3H]cholesteryl linoleate was injected intravenously into rabbits to prime the endothelial cells with labelled cholesterol, only 1-2% of the radioactivity remained in the plasma after 2 hr. 3. After 4 hr, 60.1% of the plasma radioactivity was present in HDL and 25% of this was recovered in the largest particles of HDL (fraction VI, mean particle diameter 11.6-11.8 nm). 4. The concentration of these largest particles of HDL, rich in apolipoprotein E, were also relatively increased in acetyl-LDL-treated rabbits when compared to controls (P < 0.01). 5. In control in vitro experiments, 62.2% of the radioactivity recovered in HDL was associated with subfractions IV and V (mean particle diameter 10.2-10.8 nm) while only 5% was present in fraction VI. 6. The results show that large HDL particles enriched with apo E contain a large proportion of cholesterol previously supplied to hepatic and peripheral endothelial cells. 7. This study demonstrated that the rabbit provides a useful animal model for the study of the metabolism of subfractions of HDL in relation to reverse cholesterol transport. PMID- 8365120 TI - A comparative study of free radicals in vertebrates--II. Non-enzymatic antioxidants and oxidative stress. AB - 1. The three main non-enzymatic endogenous soluble antioxidants and three estimators of oxidative stress were measured in the liver, lung and brain of seven animal species of different vertebrate classes. 2. The more concentrated antioxidant was GSH, followed by ascorbate and finally by uric acid. Liver showed higher levels of GSH and uric acid than the other two organs in the majority of the species. 3. GSSG/GSH ratio was highest in lung, probably due to the high pO2 prevalent in the tissue. Nevertheless, this did not result in higher tissue peroxidation, suggesting that the lung antioxidants are capable of coping with a high tissue pO2. 4. Tissue peroxidation was maximal in the brain when assayed by the TBA test, but this was not confirmed by HPLC of malondialdehyde (MDA). HPLC resulted in much lower MDA values than TBA. PMID- 8365121 TI - Multiple types and forms of odorant-binding proteins in the Old-World porcupine Hystrix cristata. AB - 1. Eight new proteins have been identified and purified from the nasal tissue of the old-world porcupine. 2. All of them show good binding activity to tritiated 2 isobutyl-3-methoxypyrazine. 3. They show values of molecular mass, in denaturing conditions, between 18 and 23 kDa, and of isoelectric points between 4.2 and 4.6. 4. This represents the first example of more than two odorant-binding proteins (OBPs) found in the same animal species and could support a discriminating function of these proteins in the process of odour perception. PMID- 8365122 TI - Nickel sensitivity and the implantation of orthopaedic prostheses. AB - There is no evidence that nickel-sensitive patients, when given a modern plastic to-stainless-steel hip replacement, develop cutaneous reactions or loosening of their prostheses. However, eczema is occasionally seen with static metal prostheses and eruptions sometimes accompanied the use of the older types of joint prosthesis. Modern plastic-to-metal joint replacements rarely cause sensitization to the composite metals. In the rare instances when this has been detected by patch testing, the affected patients have not developed eczema or loosening of their prostheses. PMID- 8365123 TI - Footwear dermatitis. AB - We conducted a study to determine the prevalence and clinical patterns of footwear dermatitis, patch testing 50 patients with suspected footwear dermatitis and 30 controls with 22 allergens of a shoe series (Chemotechnique Diagnostics AB, Malmo, Sweden). The overall prevalence among contact dermatitis cases was 11.7%. The dorsa of the feet and toes were the commonest sites involved. 70% of patients showed sensitivity to footwear allergen(s), as opposed to 6.67% of controls. Potassium dichromate and colophony were the commonest sensitizers. Other sensitizers were the rubber accelerators 2-mercaptobenzothiazole (MBT) and diphenylguanidine (DPG) and a dye p-aminoazobenzene. Of the 23 patients patch tested with pieces or scrapings of footwear, only 3 showed positive reactions. We recommend that there should be primary and secondary footwear screening series to detect the responsible allergens, with the ultimate objective of providing correct nonallergenic footwear for our patients, with the help of manufacturers and research institutes. PMID- 8365124 TI - Contact allergy to a fatty acid ester component of cutting fluids. AB - 6 patients employed in the metalworking industry developed a hand dermatitis after exposure to a vegetable-oil-based cutting fluid. After thorough investigation, including patch testing with components in the cutting fluid as well as an oil and cutting fluid series, contact allergy was demonstrated to a fatty acid ester EM-550 in the cutting fluid. PMID- 8365125 TI - Occupational allergic contact dermatitis caused by exposure to acrylates during work with dental prostheses. AB - Between 1974 and 1992, we were consulted by 4 patients (an orthodontist, 2 dental technicians and a dental worker trained in-house) who had developed occupational allergic contact dermatitis from working with dental prostheses. All patients had positive allergic patch test reactions to methyl methacrylate (MMA), the acrylate which is the most widely used in work with prostheses. All but the orthodontist also reacted to dimethacrylates, which are used in cross-linked dental prostheses. The last patient, investigated in 1992, had been exposed mainly to light-cured acrylics, which are similar in composition to dental composite resins. These acrylics, only recently introduced into prosthetic work, contain more potent acrylic sensitizers than MMA. Accordingly, dental personnel working with prostheses may face a higher risk of sensitization than previously. To detect cases of occupational allergic contact dermatitis, we suggest that patients working with dental prostheses should be patch tested with MMA, 2 hydroxyethyl methacrylate, dimethacrylates, epoxy acrylates and urethane acrylates. PMID- 8365126 TI - Long-lasting allergic patch test reaction caused by gold. AB - Allergic contact dermatitis caused by gold is rare, and only isolated cases have been reported. Patch testing with gold may cause a long-lasting reaction. The purpose of this study is to describe a well-studied case of gold allergy caused by dental gold crowns. A gold-sensitized patient and a non-sensitized control subject were examined using patch tests, immunohistochemistry, electron microscopy and blast transformation reactions. Sodium thiosulfate, auranofin and sodium thiomalate gave positive patch test reactions. Immunohistochemistry and electron microscopy were performed from biopsies taken from allergic patch test reactions caused by gold sodium thiosulfate 1 day and 17 days after applying the patches, from normal skin and from a 17-day-old allergic patch test reaction caused by ammonium persulfate. Down-regulation had taken place by 17 days in the allergic ammonium persulfate reaction, but not in the 17-day allergic gold test reaction. The patient reacted to all but one of the gold-induced blast transformation tests, sodium chloroaurate being non-inductive. The non-sensitized control subject did not exhibit any reactions. In conclusion, gold sodium thiosulfate, gold sodium thiomalate and auranofin can be used as patch test substances for gold allergy, though long-lasting allergic patch test reactions may develop. In vitro gold salt induced blast transformation is an alternative test for gold allergy. The slow down-regulation of the allergic patch test reactions needs to be studied further. PMID- 8365127 TI - Fixed drug eruption due to allylisopropylacetylurea. AB - We report a case of fixed drug eruption due to allylisopropylacetylurea. A 21 year-old female developed purplish-red round eruptions on her neck and left thigh after taking an analgesic containing isopropylantipyrine, allylisopropylacetylurea, phenacetin and anhydrous caffeine. Patch testing with the analgesic and its ingredients on the eruptive area showed positive reactions to the analgesic and allylisopropylacetylurea, while patch testing on the non eruptive area showed negative reactions. We diagnosed her condition as a fixed drug eruption due to allylisopropylacetylurea in an analgesic. PMID- 8365128 TI - A standard protocol for phototoxicity testing. Results from an interlaboratory study. AB - Based on experience accumulated in a number of laboratories, a standardized protocol for phototoxicity testing in experimental animals by the dermal route is presented. By conducting a limited interlaboratory study, demonstrating a high degree of consistency using 8-methoxypsoralen (8-MOP) and acridine, the sensitivity and reproducibility of the proposed methodology is demonstrated. Important aspects of performing phototoxicity testing are discussed. PMID- 8365129 TI - Allergic contact dermatitis from picric acid. PMID- 8365130 TI - A new source of sensitivity to epoxy resin. PMID- 8365131 TI - Sensitization to nickel from stainless steel ear-piercing kits. PMID- 8365132 TI - Contact urticaria from sodium fluoride. PMID- 8365133 TI - HLA-A, -B and -DR antigens in hydrocortisone contact hypersensitivity. PMID- 8365134 TI - Occupational allergic contact dermatitis from epoxy varnishes. PMID- 8365135 TI - Size of the test area does not affect the result of the repeated open application test. PMID- 8365137 TI - The influence of climatic factors on patch test results in Athens. PMID- 8365136 TI - Contact dermatitis from UV-A and UV-B filters in a patient with erythropoietic protoporphyria. PMID- 8365138 TI - Gold-stimulated production of granulocyte/macrophage colony-stimulating factor by peripheral blood mononuclear cells from a patient with gold contact dermatitis. PMID- 8365140 TI - Pigmented contact dermatitis from deodorant. PMID- 8365139 TI - Contact allergy due to 4-N,N-dimethylaminobenzene diazonium chloride and thiourea in diazo copy paper. PMID- 8365141 TI - A study of attenders at an occupational dermatology clinic. PMID- 8365142 TI - Contact dermatitis from tioconazole mimicking "one hand two feet syndrome". PMID- 8365143 TI - Contact allergy to tea tree oil. PMID- 8365144 TI - Influence of area of application of allergen on sensitization in contact dermatitis. PMID- 8365145 TI - Intradermal testing in the diagnosis of allergic contact dermatitis. A reappraisal. AB - Contact hypersensitivity may be diagnosed with patch testing or intradermal testing. Although these methods have been used earlier in parallel, patch testing has gradually become the only method in routine diagnosis of contact allergy. Recent findings in corticosteroid contact hypersensitivity have shown that patch testing is not always an optimal method, especially when poor penetrants are used. Therefore, a reappraisal of intradermal testing is presented, based on the literature. Studies employing both patch and intradermal testing are reviewed and the advantages and disadvantages of intradermal tests as compared to patch tests in contact allergy diagnostics are discussed. We find that it might be worthwhile to evaluate whether contact allergy to compounds other than corticosteroids may be easier to detect with intradermal than patch test. PMID- 8365146 TI - Dermatitis in bulb growers. AB - A damaged skin forms a health hazard in flower-bulb growers as it enables higher permeation rates for pesticides than normal skin. Therefore, an investigation was performed into the skin condition of 103 bulb growers and 49 controls. Contact dermatitis of the hands was of the same order (11 and 10%) in both groups. However, minor signs of dermatitis were seen more often in bulb growers (30 versus 8%, p < 0.05). Most growers had contact with narcissus sap during the investigation. This irritant sap, as well as many other skin contacts with irritants such as hyacinth dust and pesticides, seemed to be responsible for many skin complaints. Contact sensitization was suspected in 19 growers and 3 controls. Patch tests showed that contact sensitization existed to pesticides in probably 10, and to flower-bulb extracts in 4 growers. Reactions to propachlor were not regarded as very reliable as the test concentration seemed to be marginally irritant. There were only a few allergic reactions to narcissus (3) and tulip (2) and none to hyacinth. This investigation showed that minor irritant contact dermatitis was frequent in bulb growers, and indicated that contact sensitization to pesticides and bulbs seemed to be a less frequent but important cause of dermatitis. PMID- 8365147 TI - Nickel sensitization and ear piercing in an unselected Danish population. Glostrup Allergy Study. AB - The study aimed at evaluating nickel sensitization and ear piercing in an unselected population. A questionnaire and ready-to-apply patch tests (TRUE-Test) were mailed to 793 subjects, aged 15 to 69 years. A total of 567 (71.5% out of the 793) were patch tested. The tests were read 2 days after application. Nickel sensitization was diagnosed in 11.1% of the females and in 2.2% of the males. Independent of sex, old age was associated with a lower risk of nickel sensitization (p < 0.01). The risk of nickel sensitization was independent of a history of flexural eczema (p > 0.5). Ear piercing was more common in the young than in the older age groups, ranging from 30.5% to 0.0% in men, and from 91.5% to 42.9% in women. Sensitization to nickel was found in 14.8% of those with pierced ears as compared to 1.8% among those without pierced ears. When adjusted for the effects of sex and age, the risk of nickel sensitization among those with pierced ears remained significantly increased and the odds ratio value was 4.5; the 95% confidence interval of the odds ratio value was 1.5 to 13.0. The study confirmed that nickel sensitization in the general population is common, particularly among women. Ear piercing is probably an important risk factor for nickel sensitization. PMID- 8365148 TI - Alcohol vehicles in tests for non-immunological immediate contact reactions. AB - In a search for vehicles that might enhance the sensitivity of human skin tests for nonimmunological immediate contact reactions, benzoic acid was tested in 17 liquid vehicles on 16 medical students using the open application test method on the upper back. The results were read visually and the change in blood flow was measured using a laser-Doppler flowmeter 20, 40 and 60 min after application of the test substances. 2-propyl alcohol (isopropanol), ethyl alcohol (ethanol), 1,2 propylene glycol and water were mixed to form alcohol, alcohol/water, alcohol/alcohol, alcohol/propylene glycol and propylene glycol/water vehicles. The reactions were stronger in the alcohol/water vehicles than in the alcohols as such. The addition of 25% propylene glycol to isopropanol and ethanol had the greatest enhancing effect on the reactions. Ethanol has been the most popular liquid vehicle in tests for non-immunological immediate contact reactions, but at least with benzoic acid, stronger reactions can be elicited if alcohol/propylene glycol or alcohol/water mixture are used. PMID- 8365149 TI - Studies of new short-period method for delayed contact hypersensitivity assay in the guinea pig. (2). Studies of the enhancement effect of cyclophosphamide. AB - The enhancement effect of cyclophosphamide on the delayed contact hypersensitivity reaction of chemical compounds was studied in Hartley albino guinea pigs. A series of assay procedures, combining the AP2 test (adjuvant and 24-h occlusive patch 2x test, as previously reported) with intraperitoneal cyclophosphamide administration, were examined. The newly developed method was as follows; cyclophosphamide 200 mg/kg intraperitoneal administration 3 days before the 1st sensitization of the AP2 test (cyclophosphamide, adjuvant and 24-h occlusive patch 2x test: CAP2 test). Comparing the CAP2 test with the AP2 test, the cumulative contact enhancement test (CCET) and the guinea pig maximization test (GPMT), the CAP2 test equally and/or better enabled the detection of allergenicities not only of strong allergens such as bromostyrol, citronellal, p phenylenediamine and formaldehyde, but also of weak allergens such as benzyl salicylate and p-aminobenzoic acid ethyl ester. Acanthosis and spongiosis in the epidermis and mononuclear cell infiltration into the dermis at the skin reaction site were histopathologically observed. Cyclophosphamide effectively enhanced the delayed contact hypersensitivity reaction of weak allergens. PMID- 8365150 TI - Guinea pig maximization test of the bark extract from pawpaw, Asimina triloba (Annonaceae). AB - Several acetogenins, characteristic of the Annonaceae, have been found to exhibit pesticidal and feeding-deterrent activities against a variety of pests and are undergoing commercial development as pesticides. The sensitizing potential of one of these plants, pawpaw, Asimina triloba Dunal, was examined in the current study. The potential of Fraction F020 (a pesticidal crude extract of pawpaw stem bark) to sensitize and elicit an allergic contact dermatitis response was determined by using a modified guinea pig maximization test (GPMT). Fraction F020 is a weak sensitizer and the active compound, asimicin, a trihydroxy bistetrahydrofuran fatty acid gamma-lactone, is a weak irritant. PMID- 8365151 TI - Contact allergy to aluminium in 2 brothers. AB - A 10-year-old boy reacted to aluminium Finn Chambers during routine patch testing. Further patch tests with aqueous aluminium chloride confirmed contact allergy to aluminium. The boy's 8-year-old brother also reacted to aluminium Finn Chambers. Both boys had suffered from a scaling eruption on their face and limbs since infancy. PMID- 8365152 TI - Occupational contact sensitization to ethylenediamine in a wire-drawing factory. PMID- 8365153 TI - Topical NSAID allergic contact dermatitis. Italian experience. PMID- 8365154 TI - Contact dermatitis due to Metasol D3T in a Jay cushion. PMID- 8365155 TI - Contact dermatitis from glyceryl di-isostearate. PMID- 8365156 TI - Allergic contact dermatitis following subconjunctival injection of framycetin. PMID- 8365157 TI - Achromic patch test from hydroquinone monobenzyl ether. PMID- 8365158 TI - Generalized cutaneous reaction to diltiazem. PMID- 8365159 TI - Isolated cobalt sensitivity in an etcher. PMID- 8365160 TI - Contact and photocontact allergy to dibenzoylmethanes and contact allergy to methylbenzylidene camphor. PMID- 8365161 TI - Allergic contact dermatitis in caterers. PMID- 8365162 TI - Contact dermatitis of the eyelids from resorcinol in an ophthalmic ointment. PMID- 8365163 TI - Contact dermatitis due to sensitization to lactic acid and castor oil in a wart remover solution. PMID- 8365165 TI - 'Hydrocortisone alcohol'. PMID- 8365164 TI - Etiologic agents in allergic contact dermatitis caused by eyedrops. PMID- 8365166 TI - Patch testing with glyceryl monothioglycolate. PMID- 8365167 TI - Compositae dermatitis in a Danish dermatology department in one year (I). Results of routine patch testing with the sesquiterpene lactone mix supplemented with aimed patch testing with extracts and sesquiterpene lactones of Compositae plants. AB - To investigate the frequency of Compositae sensitivity, the recently-developed sesquiterpene lactone mix (SL mix) was included in the standard patch test series. Patients with positive reactions to this or patients suspected of having a Compositae allergy were supplementarily tested with a Compositae mix, consisting of ether extracts of 5 European Compositae plants. In the first year, 686 patients were tested with the SL mix and 79 with the Compositae mix. A total of 31 Compositae-sensitive patients (4.5%) were found. The frequency of positive reactions to either of the mixes was equal, but only 17 of 30 patients tested were positive to both mixes. Testing with the individual ingredients of the Compositae mix showed frequent positive patch test reactions to feverfew, followed in order by chamomile, tansy, yarrow and arnica. The reason for this distribution is discussed and the results of standard, photo- and other plant patch tests are presented. The only partial overlap between positive reactions to the mixes emphasizes the necessity of supplementary testing in patients suspected of Compositae allergy, as well as the lack of a reliable single screening agent. Since no cases of active sensitization or irritant reactions were seen, both the SL mix and the Compositae mix may be considered suitable for routine screening of Compositae allergy. PMID- 8365168 TI - Allergic contact dermatitis from phenylephrine in a rectal ointment. PMID- 8365169 TI - A polysensitized HIV-positive patient. PMID- 8365170 TI - Allergic contact cheilitis and stomatitis from hydroquinone in an acrylic dental prosthesis. PMID- 8365171 TI - Allergic contact dermatitis from transdermal nicotine systems. PMID- 8365173 TI - Captan, a rare contact sensitizer in hairdressing. PMID- 8365172 TI - Systemic contact dermatitis from hydrocortisone. PMID- 8365174 TI - Prevention of phytophotodermatitis from celery. PMID- 8365175 TI - Occupational protein contact dermatitis from lettuce. PMID- 8365176 TI - Skin reactivity to tin chloride and metallic tin. PMID- 8365177 TI - Topical nonsteroidal antiinflammatory drugs: allergic and photoallergic contact dermatitis and phototoxicity. PMID- 8365178 TI - Nickel sensitivity in atopics, psoriatics and healthy subjects. AB - A prospective study of 552 persons was performed to study nickel allergy in atopics, with and without dermatitis, psoriatics and healthy adults. We found no statistically-significant difference in the frequency of nickel allergy between persons with atopic dermatitis, atopics without dermatitis and healthy controls. More females than men gave a history of metal intolerance and gave allergic patch test reactions. A poor correlation between history and patch test reaction was not specific for atopics. Psoriatics had a significantly lower frequency of allergic patch test reactions to nickel than healthy controls or atopics with and without dermatitis. Psoriatics should not be used as controls for atopics in studies of contact dermatitis. PMID- 8365179 TI - Contact allergy to sunscreen chemicals in photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) and polymorphic light eruption (PLE). AB - From 1989-1991, 214 patients (45 PD/AR, 54 PLE, 115 controls) were patch tested to a sunscreen series containing 9 constituents. 16/214 (7.5%) patients reacted to one or more sunscreens, with allergy being significantly more common in PD/AR patients (10/45 versus 2/54 PLE and 4/115 contact dermatitis clinic controls). The benzophenone group of sunscreens (mexenone, oxybenzone) were the most frequent sensitizers, accounting for 8 of the 27 positive patch tests observed. Clinicians should consider contact allergy to sunscreens in PD/AR patients as an explanation for exposed-site dermatitis episodes. PMID- 8365180 TI - Efficacy of skin barrier creams (II). Ineffectiveness of a popular "skin protector" against various irritants in the repetitive irritation test in the guinea pig. AB - A popular "skin protector" consisting of an emulsion-like foam of lipophilic and hydrophilic substances (Marly skin) was evaluated in a previously described repetitive irritation guinea pig model. The product failed to inhibit the irritation due to sodium lauryl sulphate and toluene. In striking contrast to the recommended use, the irritant response of sodium hydroxide was aggravated, as demonstrated by significant differences for all test parameters (clinical score for erythema and scaling, transepidermal water loss, blood flow volume). The results show that protection against chemical irritants may be quite specific and that some formulations may actually be harmful. PMID- 8365181 TI - Quantitative structure-activity relationships for skin sensitization potential of urushiol analogues. AB - The relative alkylation index (RAI), a theoretically derived parameter intended to quantify the relative extent of carrier haptenation resulting from a given dose of a given sensitizer, has previously been successfully applied to the analysis of relative sensitization potential and dose-response data for a variety of contact allergens which are directly electrophilic. Here the RAI concept is applied to analysis of data on compounds related to urushiol (i.e., 3-substituted catechols), the naturally occurring mixture of allergens responsible for contact allergy to poison ivy and poison oak. These allergens are believed to act as pro electrophiles, being oxidized to electrophilic orthoquinones in vivo. It is found that the various types of urushiol derivatives fit the same sort of RAI sensitization relationships as expected theoretically and as found previously with direct acting electrophiles. There is evidence that in many cases, the test conditions were such that overload effects, whereby the degree of sensitization induced decreases with increasing carrier haptenation, applied. It is also concluded that the question as to the relative sensitization potencies of the naturally occurring urushiols remains open. The commonly held view that with these materials, sensitization potential increases with increasing unsaturation in the 3-hydrocarbyl chain of the 3-hydrocarbyl catechols, is based on evidence that is capable of alternative interpretation. PMID- 8365183 TI - Prognosis of occupational contact dermatitis in New South Wales, Australia. AB - 570 patients with occupational contact dermatitis (OCD) were seen between 1984 and 1990 at the Skin and Cancer Foundation in Sydney. 336 (59%) were followed up 1 to 5 years later. Roughly 1/3 were healed, 1/3 were improved without complete healing, 1/4 had no change and 1/12 of the patients had deteriorated. The overall improvement rate was in excess of 70%. Data derived from these patients demonstrated that changing the work duties of patients with OCD improved their outcome (p < 0.01), whilst leaving the industry altogether resulted in a greater overall healing rate (p < 0.01). No difference existed between the outcome of irritant contact dermatitis compared with allergic contact dermatitis. Atopics as expected had a worse prognosis. The outcome in the construction industry was significantly poorer than other industries. Patients suffering from allergic contact dermatitis from chromate also had a dismal prognosis. PMID- 8365182 TI - Sesquiterpene lactone contact sensitivity: clinical patterns of Compositae dermatitis and relationship to chronic actinic dermatitis. AB - A mix of 3 sesquiterpene lactones (SL) (SL mix 0.1%) was evaluated over a 4-year period. Of 7420 patients with eczema investigated by patch testing, 135 (68 male, 67 female) (1.8%) demonstrated positive reactions, 114 (84%) considered clinically relevant. Females outnumbered males until the age of 60, after which men were more commonly affected. The clinical patterns varied from patients presenting with generalized eczema (20%) or eczema of the hands and face (24%), to patients with hand (36%) or facial eczema (11%) alone. 48 patients were investigated for suspected photosensitivity and 29 (21 male, mean age 69 years, and 8 female, mean age 66 years) had abnormal cutaneous monochromatic irradiation tests. These results highlight the varied clinical presentation of SL contact dermatitis and its association with chronic actinic dermatitis. The SL mix proved reliable and safe, supporting its inclusion in the European standard series of contact allergens. PMID- 8365184 TI - Allergic contact dermatitis from di-isodecyl phthalate in a polyvinyl chloride identity band. PMID- 8365185 TI - Stability of patch test allergens. PMID- 8365186 TI - Contact dermatitis from thioxolone. PMID- 8365187 TI - Contact allergy to sodium sulfite contained in an antifungal preparation. PMID- 8365188 TI - Allergic contact dermatitis from Biobans in Spanish metalworkers. PMID- 8365189 TI - Contact dermatitis from pilocarpine. PMID- 8365190 TI - Contact dermatitis due to dibromodicyanobutane in cucumber eye gel. PMID- 8365191 TI - In defense of the corporate author for multicenter trials. PMID- 8365192 TI - Instituting a research ethic. PMID- 8365193 TI - Tightening the clinical trial. AB - Randomized clinical trials adhere more closely to pre-agreed-on protocols than almost any other type of experiment, yet we can tighten up their analysis if we desire. If we convert the analysis into a randomization analysis--where the one set of data is analyzed many times--once as though each acceptable assignment has been employed, we can eliminate any dependence of the analysis on statistical or probabilistic assumptions. To do this effectively when many assignments could be acceptable, we can go to double randomization, in which a subset, usefully kept balanced, of acceptable assignments is selected (perhaps randomly) before data acquisition. If we have one covariate, adjustment for which answers a question that is at least as appropriate, we can easily build on this. Imperfect covariance adjustments can help almost as much as perfect ones. If it is appropriate to work with many covariate(s), it is often desirable to first construct a (few) compound covariate(s) and then work with it (them). Often we can base the coefficients in our compound covariate on the univariate regressions of response on single covariates. Doing this within each arm of the trial and pooling keeps the fitting of the final adjustment unbiased. Since we can prespecify how the compounds are to be calculated and fitted, we can do all this while retaining rigid prespecification. Prespecification, randomization, and intelligent use of covariates combined to make the resulting significance analysis of platinum standard quality. (If we want confidence statements, as we ordinarily should, it may make sense, for technical reasons, to plan for somewhat less than platinum standard quality). PMID- 8365194 TI - "Within patient"-dependent outcomes in graft occlusion after coronary artery bypass. SINBA Group. AB - In clinical trials aimed at assessing the efficacy of drugs after coronary artery grafting, statistical analysis is usually carried out on a per-patient basis and on a per-graft basis. Owing to the independence of responses among patients, the former outcome is analyzed by assuming a binomial model. However, this model cannot be directly adopted in analyzing the latter outcome because multiple vein grafts in the same patient do not act independently. It has been suggested that patients be considered as clusters of distal anastomoses, subsequently comparing the frequencies of occlusion under different treatments after adjusting the variance of each frequency for the size of the cluster. Alternatively, one can measure the intraclass (intrapatient) correlation coefficient and adopt distribution functions that include this quantity as one of the parameters. This approach has been adopted by many authors although the studies differed in the statistical model used to represent this kind of data. Two probability functions, Altham's and beta-binomial, have found wide application in different biomedical fields. Both are able to model the extrabinomial variability since their tails tend to zero more slowly than those of the binomial distribution. An alternative to adopting a specific probabilistic model consists of specifying a mixed model or a Markov-like susceptibility model. These models follow the same rationale since they assume the existence of two processes, one that causes an individual to become susceptible to occlusion, the other that determines the subsequent probability of occlusion in the individual. After presenting these models in a unified framework, this paper compares the estimates obtained by fitting the models to data gathered at coronary angiography 1 year after surgery by the SINBA group on a total of 847 saphenous vein anastomoses in 349 patients. Finally, the issue concerning the contribution of each patient to the effective sample size is discussed. PMID- 8365195 TI - Statistical design and monitoring of the Carotene and Retinol Efficacy Trial (CARET). AB - CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials. PMID- 8365196 TI - Research cost analyses to aid in decision making in the conduct of a large prevention trial, CARET. Carotene and Retinol Efficacy Trial. AB - Because of their larger study populations and longer durations, prevention trials typically are more costly than treatment trials. Thus it is important to analyze costs systematically to aid in making cost-effective decisions during the conduct of prevention trials as well as in the original design. Cost analysis must be tied to sample size estimation because costs depend on such factors as the total number of person-years of follow-up and the number of trial outcomes, which are not basic design parameters but are derived quantities resulting from sample size estimation. We illustrate the use of cost analysis to decide among options for future conduct of an ongoing prevention trial with three issues that have arisen during the Carotene and Retinol Efficacy Trial (CARET): the trade-off between extending the duration of the trial or increasing the number of participants, the effect on costs of delay in accrual, and the cost effectiveness of particular retention activities. PMID- 8365197 TI - Impact of clinical trials on medical practices. PMID- 8365198 TI - Simulating the electrical behavior of cardiac tissue using the bidomain model. AB - The complex microstructure of cardiac muscle comprised of coupled cells, enveloped by an interstitium made up of blood vessels, connective tissue, and fluid, presents some obvious problems to those interested in understanding the tissue as an electrical medium. One approach that has gained considerable favor in recent years views the tissue not as a discrete structure, but rather as two coupled, continuous domains: one for the intracellular space and the other for the interstitial space. For convenience, the averaged potentials and currents in both domains are defined at every point in space. The structure is partially preserved by assigning a conductivity tensor at each point. One advantage of using this space-averaged model is that the governing equations for the electric fields can be described by partial differential equations that on occasion lead to analytical solutions. This formal treatment of cardiac tissue as two coupled continua is referred to as the bidomain model. This article presents a mathematical description of the bidomain model and reviews the use of the model for simulating the electrical behavior of cardiac tissue. PMID- 8365199 TI - The critically ill child: a status report. PMID- 8365200 TI - The future of pediatric critical care medicine. PMID- 8365202 TI - Severe group A streptococcal infections. PMID- 8365201 TI - New treatments for sepsis. PMID- 8365203 TI - Nosocomial infections in the pediatric intensive care unit: etiology and prevention. PMID- 8365204 TI - Update: meningitis. PMID- 8365205 TI - Pediatric AIDS and critical care. PMID- 8365206 TI - Physiology of cardiopulmonary resuscitation in children. PMID- 8365207 TI - Acid-base balance during cardiopulmonary resuscitation. PMID- 8365208 TI - Outcome of pediatric cardiopulmonary resuscitation. PMID- 8365209 TI - Advances in pediatric cardiac surgery. PMID- 8365210 TI - Cardiac surgery and postoperative management. PMID- 8365211 TI - Management of low cardiac output after cardiac surgery. PMID- 8365212 TI - Tools for predicting outcome in the neurologically injured child. PMID- 8365214 TI - Cranial imaging and Doppler sonography in the critically ill infant. PMID- 8365213 TI - Neurologic intensive care: status epilepticus. PMID- 8365215 TI - A pragmatic approach to the treatment of the child with hypoxic-ischemic encephalopathy. PMID- 8365216 TI - Brain death in the pediatric patient: historical, sociological, medical, religious, cultural, legal, and ethical considerations. PMID- 8365217 TI - The intensivist's system. PMID- 8365218 TI - Vascular endothelium as a target and effector organ. PMID- 8365220 TI - New immunosuppressive agents and infection in solid organ transplantation. PMID- 8365219 TI - Management of fulminant hepatic failure in children--an analysis of 56 cases. PMID- 8365221 TI - Lung transplantation in children. PMID- 8365222 TI - Postoperative liver transplant care. PMID- 8365223 TI - Update on cardiac transplantation in infants and children. PMID- 8365224 TI - Life, death, and solid organ transplantation without brain death. PMID- 8365225 TI - Relationships between stress responses and clinical outcome in newborns, infants, and children. PMID- 8365226 TI - Patterns of the metabolic and endocrine stress response to surgery and medical illness in infancy and childhood. PMID- 8365227 TI - Hemodynamic responses to perioperative pain and stress in infants. PMID- 8365228 TI - Adult respiratory distress syndrome in newborn infants. PMID- 8365229 TI - Respiratory management for low-birth-weight infants. PMID- 8365230 TI - Airway management during transport. PMID- 8365231 TI - New modes of mechanical ventilation for severe respiratory failure. PMID- 8365232 TI - Newer modes of mechanical ventilation for patients with adult respiratory distress syndrome. PMID- 8365233 TI - Lung mechanics and mechanical ventilation. PMID- 8365234 TI - High-frequency ventilation. PMID- 8365235 TI - Pulmonary hypertension: physiologic or pathologic disease? PMID- 8365236 TI - Inhaled nitric oxide for treatment of pulmonary artery hypertension in the newborn and infant. PMID- 8365237 TI - Use of extracorporeal membrane oxygenation for preoperative stabilization of congenital diaphragmatic hernia. PMID- 8365238 TI - Congenital diaphragmatic hernia: are there reliable clinical predictors? PMID- 8365240 TI - Extracorporeal respiratory assistance for pediatric acute respiratory failure. PMID- 8365239 TI - Extracorporeal circulatory support in children in intensive care. PMID- 8365241 TI - Communication between physician, patient, and family in the pediatric intensive care unit. PMID- 8365242 TI - Caring for parents of critically ill children. PMID- 8365243 TI - Child/family advocacy: ethical issues, practical strategies. PMID- 8365244 TI - Managing the intensive care unit: nurse/physician collaboration. PMID- 8365245 TI - Collaboration between nurses and physicians in Europe. PMID- 8365246 TI - Managing the intensive care unit: physician-nurse collaboration. PMID- 8365247 TI - Bereavement: role of the nurse in the care of terminally ill and dying children in the pediatric intensive care unit. PMID- 8365248 TI - Initial assessment and stabilization of the pediatric trauma patient. PMID- 8365249 TI - Pediatric intensive care nursing. PMID- 8365250 TI - Prehospital care of the injured child: an analysis of selected premises. PMID- 8365251 TI - Retention of critical care staff. PMID- 8365252 TI - Outcome assessment. PMID- 8365253 TI - Withdrawing mechanical ventilation. PMID- 8365254 TI - Present trends in fluid therapy, metabolic care, and prevention of infection in burned children. PMID- 8365255 TI - Ecological impact of pediatric intensive care. PMID- 8365256 TI - Molecular pathophysiology in critical care illness. PMID- 8365257 TI - Clinical research in the critical care environment. PMID- 8365258 TI - Outcome and quality assurance standards. PMID- 8365259 TI - Pediatric intensive care in Argentina. PMID- 8365260 TI - Pediatric intensive care around the world: Australia. PMID- 8365261 TI - Impact of national health system financing on quality of care in the intensive care unit: the German experience. PMID- 8365262 TI - Overview of pediatric intensive care from around the world: Germany. PMID- 8365263 TI - Developing pediatric emergency services in Israel: goals and state of the art. PMID- 8365264 TI - International standard of quality in the pediatric intensive care unit: a model for pediatric intensive care units in South America. PMID- 8365265 TI - Overview of pediatric intensive care in Thailand. PMID- 8365266 TI - A new role for the pulmonologist. Bringing bioethics back to the bedside. PMID- 8365267 TI - Preflight medical screening of patients. PMID- 8365268 TI - Bronchoalveolar lavage fluid in HIV-infected patients. "Cytokine soup". PMID- 8365269 TI - Preoperative evaluation of cardiovascular reserve in the elderly. PMID- 8365270 TI - Pressure-controlled inverse ratio ventilation. What have we learned? PMID- 8365271 TI - Excessive daytime sleepiness, upper airway resistance, and nocturnal arousals. PMID- 8365272 TI - Chronic Pneumocystis carinii pneumonia in AIDS. AB - The clinical and radiologic presentation as well as the macroscopic and histologic characteristics of lung parenchyma in three HIV-infected patients with Pneumocystis carinii pneumonia (PCP) are detailed. The distinguishing clinical feature in these patients was a prolonged stable clinical course of the disease over at least 4 to approximately 24 months. Serial chest radiographs in two patients demonstrated persistent focal radiographic lesions. In one patient blebs in both upper lobes were not recognized until thoracoscopy/thoracotomy was performed. Biopsy specimens of affected areas revealed extensive interstitial fibrosis, occasional giant cell reactions, and honeycombing. In view of the combined clinical, radiologic, macroscopic, and histologic patterns, it is suggested that these patients had a chronic productive form of PCP rather than the well-known acute presentation of the disease. Data from the literature confirm the impression that atypical histologic lesions of PCP, either of a productive or destructive nature, are frequently related to a prolonged clinical course. It is unlikely that prophylactic pentamidine contributes to this entity. Coinfection with other pathogens may have a role. Given the recent evidence on augmented release of tumor necrosis factor a (TNFa) in HIV-associated pulmonary complications, it is speculated that TNFa may be of importance in producing focal fibrosis in Pneumocystis infection of the lung. PMID- 8365273 TI - Concentric tracheal and subglottic stenosis. Management using the Nd-YAG laser for mucosal sparing followed by gentle dilatation. AB - Treatment of tracheal stenosis varies with the type and extent of the disease. Tracheostomy with stents, end-to-end anastomosis, or extensive reconstructive procedures often is required, especially when tracheomalacia is present. High recurrence rate is associated with relatively less invasive endotracheal treatments, such as bougie dilatation or total laser ablation. Mucosal sparing technique using Nd:YAG laser photodissection (LPD) and gentle dilatation (GD) can provide durable successful results in selected patients with benign concentric tracheal stenosis (CTS). In our study of 18 patients with CTS, 12 were successfully treated with Nd:YAG LPD and GD. Of these patients, eight required a single treatment while four required two or more treatments. No patients required new tracheostomy to carry out the procedure. Follow-up periods ranging from 2 to 85 months (mean: 32.6 +/- 1.5 months) for 12 successfully treated patients have revealed no recurrence of their stenosis. Lengthy scars (> 1 cm) and tracheomalacia were the clinical features common to those patients who failed the treatment. We advocate the use of Nd:YAG LPD in conjunction with "gentle" rigid bronchoscopic dilatation as the initial treatment of CTS. PMID- 8365274 TI - Three cases of paradoxical vocal cord adduction followed up over a 10-year period. AB - Paradoxical vocal cord adduction (PVCA) is a rare disorder that may present with symptoms similar to asthma. Incorrect diagnosis may result in patients being unwittingly treated with prolonged high doses of antiasthma medication. PVCA probably forms part of a spectrum of uncommon and complex breathing disorders related to laryngeal dysfunction. Herein, we describe three cases of PVCA that illustrate the spectrum of clinical and physiologic presentation and the long term natural history over a 10-year follow-up period. We conclude that PVCA, contrary to previous reports, is not always a benign condition; it may feature marked hypoxemia, fail to respond to previously advocated therapeutic strategies, and can persist on a long-term basis. PMID- 8365275 TI - Infection in the transplanted and native lung after single lung transplantation. AB - OBJECTIVE: To analyze a single-center experience with infectious complications of single lung transplantation (SLT) with special emphasis on risk factors for infection in the transplanted and native lung. DESIGN: Consecutive case series. SETTING: University teaching hospital. PATIENTS: Fifteen consecutive SLT recipients (mean age, 43 years; 9 men and 6 women). Mean follow-up was 337 days. RESULTS: Fifteen patients had 24 infectious episodes (1.6 per patient) of which 83 percent were life-threatening, 79 percent involved the lung, airway, or pleural space, and 79 percent occurred in the first 4 months after transplantation. Despite this high infectious morbidity, there were no infectious deaths. The most important infections were bacterial pneumonia (n = 10), cytomegalovirus (CMV) pneumonia (n = 5), and bronchial anastomotic infections (n = 3). Significant risk factors for bacterial pneumonia were a diagnosis of primary or secondary pulmonary hypertension (p < 0.05) and the presence of airway complications of stenosis or dehiscence (p < 0.05). No risk factors for overall lung infections were identified. The native lung was involved in 6 of 16 lung infections and was the exclusive site of infection in 4 cases. Underlying disease in the native lung may have predisposed to infection at that site by a mechanism of inadequate blood flow or impaired ventilation. Three bronchial anastomotic infections (Pseudomonas, Candida, Aspergillus) occurred, all with dehiscence of the anastomosis. These were highly morbid but resolved with antibiotics, stent placement, and surgical retention in two of the three cases. The five episodes of CMV pneumonia caused mild (four patients) or moderate (one patient) dysfunction and responded to antiviral agents without relapse. CONCLUSION: The frequency, complexity, and morbidity of infections after SLT were great, but most infections were manageable and good outcomes were achieved. A pretransplant diagnosis of pulmonary hypertension or posttransplant occurrence of bronchial stenosis or dehiscence were associated with a higher rate of bacterial pneumonia. The underlying disease in the native lung may predispose to infection at that site. PMID- 8365277 TI - Left main coronary flow velocity associated with stenosis. Evaluation by transesophageal color-guided pulsed Doppler technique. AB - To quantitatively estimate the extent of left main coronary artery (LMCA) stenosis, flow velocity of the LMCA in 33 patients was analyzed by a transesophageal color-guided pulsed Doppler technique. In 11 of 20 patients with LMCA stenosis, coronary flow velocity could be measured. The peak diastolic flow velocity at the stenotic segments was 90 +/- 32 (SD) cm/s which was significantly greater than that at the nonstenotic segments (n = 13; 34 +/- 8 cm/s; p < 0.01), and was correlated with the angiographically determined percentage of diameter stenosis of the vessel which ranged from 52 to 90 percent (r = 0.77; y = 6.34 square root of x + 10.4; p < 0.01). These results suggest that acceleration of flow velocity at the point of stenosis may be correlated with the severity of the stenosis. Measurement of flow at the point of stenosis by transesophageal color guided pulsed Doppler technique may facilitate the quantitative assessment of LMCA stenosis, although its sensitivity requires improvement. PMID- 8365276 TI - The impact of intraoperative autotransfusion on cardiac surgery. A prospective randomized double-blind study. AB - The effect of intraoperative autotransfusion during coronary artery bypass grafting was studied in a randomized double-blind trial involving 38 patients. Nineteen patients had the collected RBCs washed and autotransfused (autotransfusion group), while the remaining patients had their washed cells discarded (control group). Postoperative hemoglobin and hematocrit values were similar. Exposure to banked blood was markedly decreased in the autotransfusion group compared with the control group. In addition, the mean volume of banked packed RBCs transfused per patient was significantly less in the autotransfusion group compared with the control group. Platelet utilization also was markedly decreased in the autotransfusion group. Cryoprecipitate and fresh frozen plasma utilization also was less in the autotransfusion group than in the control group, but this did not reach statistical significance. We conclude that the intraoperative use of autotransfusion decreases the volume of homologous blood products transfused, which results in reduced exposure of the patients to banked blood products. PMID- 8365278 TI - Predicting complications after pulmonary resection. Preoperative exercise testing vs a multifactorial cardiopulmonary risk index. AB - Recent studies have used preoperative cardiopulmonary exercise testing to improve risk assessment of pulmonary resection for lung cancer. These studies have demonstrated inconsistent correlation between peak oxygen uptake (VO2) and postoperative complications but have not systematically examined other methods of risk stratification. We analyzed the findings in 42 patients who had cardiopulmonary exercise testing prior to lung cancer resection. Preoperative clinical data combining pulmonary factors (obesity, productive cough, wheezing, tobacco use, ratio of the forced expiratory volume in 1 s over the forced vital capacity [FEV1/FVC] < 70 percent, and PaCO2 > 45 mm Hg), and an established cardiac risk index were used to generate a cardiopulmonary risk index (CPRI). When analyzed using the risk index, the incidence of postoperative complications increased with higher CPRI scores. Those with a CPRI of 4 or greater were 22 times more likely to develop a complication, compared to a CPRI of less than 4 (p < 0.0001). We found that patients with a peak VO2 less than 500 ml/m2/min (body surface area) were 6 times more likely to experience a cardiopulmonary complication (p < 0.05). With multiple logistic regression analysis, peak VO2 was not an independent predictor of postoperative complications. Analysis also demonstrated that a CPRI of 4 or greater was associated with significant reductions in peak VO2. We conclude that both the peak VO2 during cardiopulmonary exercise testing and a multifactorial CPRI are highly predictive of complications after lung resection. Adding the peak VO2 did not enhance the risk estimation generated by the CPRI. The association between postoperative complications and peak VO2 may be explained by the correlation between identifiable cardiopulmonary disease (CPRI) and reduced oxygen uptake with exercise. PMID- 8365279 TI - Preoperative evaluation of cardiac failure and ischemia in elderly patients by cardiopulmonary exercise testing. AB - Major surgery in the elderly continues to have a high mortality rate. Preoperative myocardial ischemia is a known risk factor. Cardiac failure is also a risk factor, but is difficult to quantify objectively. One hundred eighty-seven elderly surgical patients were evaluated for cardiac failure by cardiopulmonary exercise testing (CPX). The overall mortality in these patients was 7.5 percent. If three deaths secondary to surgical causes are excluded, mortality was 5.9 percent. There were 55 patients in whom the anaerobic threshold (AT) was less than 11 ml/min/kg; of these, 10 died, a mortality rate of 18 percent. There were 132 patients with an AT of greater than 11 ml/min/kg and of these, 1 patient died, giving a mortality rate of 0.8 percent (p < 0.001). A low AT associated with preoperative ischemia resulted in the death of 8 of 19 patients, a mortality rate of 42 percent. When the ischemia was associated with the higher AT, then 1 patient out of 25 died, a mortality rate of 4 percent (p < 0.01). Both preoperative ischemia and preoperative cardiac failure are independent risk factors for perioperative mortality in the elderly. PMID- 8365280 TI - Relationship of resting lung mechanics and exercise pattern of breathing in patients with chronic obstructive lung disease. AB - To investigate the influence of resting pulmonary mechanics on the pattern of breathing during exercise in chronic obstructive pulmonary disease (COPD), we studied 29 patients with moderate to severe COPD (FEV1 50 +/- 20 percent predicted), and 10 normal subjects. Lung mechanics were studied using esophageal balloon technique and body-box. Incremental exercise testing was performed to exhaustion. As minute ventilation (VE) increases, COPD patients with the highest pulmonary resistance (RI) or lowest elastic recoil pressure (PL), used a greater tidal volume/vital capacity ratio (VT/VC) than the COPD patients with more normal RL or lowest PL. To describe the breathing pattern during exercise, an exponential constant (K) describes the rates of increase in VT/VC ratio with increasing VE, calculated according to the equation VT = VC(1-e-KVE). The K values achieved by COPD patients were higher than in normal subjects. In addition, K value correlated negatively with the resting FEV1 and FVC of COPD patients. When COPD patients were grouped according to their K values, it was revealed that patients with high K values generated greater VT/VC ratio and also have the most abnormal resting lung mechanics. These results suggest that the exercise breathing pattern in COPD patients is significantly influenced by the degree of impairment of resting lung mechanics. PMID- 8365281 TI - Rapid resolution of hyperkinesis after exercise. Two-dimensional echocardiographic studies in normal subjects. AB - Abnormal wall motion detected with exercise echocardiography identifies ischemic myocardium, while normal myocardium exhibits hyperkinetic motion. The normal, hyperkinetic response to exercise is transient and is predictive of an excellent prognosis. However, there are few data on the duration of the hyperkinesis after peak exercise. Our purpose was to determine the time course of wall thickening after exercise in eight normal subjects with two-dimensional echocardiography. Percentage of wall thickening increased from 53 +/- 24 percent at baseline to 82 +/- 24 percent at 0 to 2 min postexercise (p < 0.001 vs baseline) and then decreased to 64 +/- 27 percent at 2 to 4 min, and 54 +/- 20 percent at 5 to 7 min (both NS vs baseline). We conclude that (1) systolic wall thickening is maximal within the initial 2 min following peak exercise, and (2) accurate identification of hyperkinetic, normal myocardium with exercise echocardiography requires immediate postexercise imaging. PMID- 8365282 TI - Complications of anticoagulation for pulmonary embolism in low risk trauma patients. AB - Trauma patients are at significant risk for deep venous thrombosis (DVT) and pulmonary embolism (PE). Anticoagulation is standard therapy for DVT/PE, but may cause severe complications. We reviewed the course of 70 trauma ICU patients treated over a 28-month period. Thirty-six patients (51.4 percent) were treated by continuous IV heparin and/or oral warfarin. Of these, 13 patients (36 percent) developed complications requiring termination of anticoagulation. These included recurrent PE (four), subdural hematomas (three), hemothorax (two), heparin induced thrombocytopenia (one), hemorrhagic pericardial effusion (one), retroperitoneal hematoma (one), and sudden unexplained drop in hemoglobin and shock (one). All patients with subdural hematomas had no prior evidence of head injury on brain computed tomography. All patients with recurrent PE received adequate anticoagulation therapy. Age > 55 was associated with increased risk of complications (8 of 13; p = .02:chi 2). Thirty-four other patients (48.6 percent) received inferior vena caval filters with no related complications or deaths. Anticoagulation for DVT/PE should be used selectively in trauma patients and avoided in elderly patients. Such patients should undergo early caval filter placement. PMID- 8365283 TI - Anti-CEA immunoscintigraphy might be more useful than computed tomography in the preoperative thoracic evaluation of lung cancer. A comparison between planar immunoscintigraphy, single photon emission computed tomography (SPECT), and computed tomography. AB - While a clinical, plain radiographic, and bronchoscopic assessment yields most of the essential information needed in lung cancer, computed tomography (CT) of the thorax provides diagnostic information previously unobtainable, potentially capable of reducing the number of explorative thoracotomies. In a few recent studies, immunoscintigraphy with anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies (MA) has shown remarkable staging potential. To compare the diagnostic accuracy of the two techniques, we photoscanned with indium-111 (111In)-labeled-F(ab')2 fragments of the murine anti-CEA MA FO23C5 45 patients, who were pathologically assessed for possible loco-regional extension of lung cancer. Both planar and single photo emission computed tomography (SPECT) images were obtained. Additionally, CT of the thorax (contiguous CT slices, 10 mm thick, from the lung apices to the upper abdomen), and other routine tests of preoperative evaluation were obtained. On the basis of 37 (N1, T3, and T4), 38 (N2), and 12 (N3) pathologically documented sites, an accuracy of 65, 76, 92, 78, and 86 percent (SPECT images), and 62, 68, 42, 78, and 84 percent (CT images) was calculated (figures are relevant to N1, N2, N3, T3, and T4 disease, respectively). Thus, both techniques shared a significant margin of error in almost all the categories of evaluation; however, immunoscintigraphy showed equivalent, and, in the lymph node assessment, superior results to CT. A marginal improvement of diagnostic accuracy was recorded combining the three techniques in one case (SPECT plus planar immunoscintigraphic images), while there was no benefit in any possible integration of CT and immunoscintigraphic images. In patients with peripheral nonsquamous cell cancers, the accuracy of anti-CEA immunoscintigraphy was of 90 percent or higher. Variations in the modality of performing immunoscintigraphy, such as changes in the dose of antibody fragments to be injected, in the percentage of radiolabeling, or in the time of imaging, affected the quality of immunoscintigraphic series, and the consequent interpretation of findings. At the present time, there are very few reliable tests capable of selecting patients to proceed directly to thoracotomy or to receive some intermediate surgical test, such as a prior mediastinoscopy. Traditionally, CT has been this type of "filter-test." If current findings will be confirmed in future studies, anti-CEA immunoscintigraphy might replace CT in the evaluation of particular subgroups of patients, such as patients with peripheral nonsquamous cell bronchogenic carcinoma. PMID- 8365285 TI - Effect of corticosteroids on IL1 beta and TNF alpha release by alveolar macrophages from patients with AIDS and Pneumocystis carinii pneumonia. AB - The mechanisms by which corticosteroids (CCs) improve the outcome of AIDS patients with severe Pneumocystis carinii pneumonia (PCP) are unclear. We studied IL1 beta and TNF alpha release from alveolar macrophages (AMs) of patients receiving CCs for the treatment of PCP and also the effect of in vitro hydrocortisone on this release. Cytokine release from AMs of AIDS patients with pulmonary complications not receiving CCs (group 1) was compared with that from AM of those receiving CCs for PCP (group 2). The AMs of HIV-negative normal subjects (group 3) served as controls. All participants were nonsmokers or exsmokers. We found that lipopolysaccharide-stimulated AM from group 2 released significantly less interleukin-1 beta (IL1 beta) and tumor necrosis factor alpha (TNF alpha) than AM from group 1 and was similar to that from group 3. There was a significant positive correlation between the amount of TNF alpha and IL1 beta released. The presence of HC in the culture medium reduced in vitro IL1 beta and TNF alpha release from stimulated AM of the three groups. Thus, stimulated AMs from AIDS patients who receive CCs for treatment of PCP release significantly less IL1 beta and TNF alpha than AM from patients not receiving CCs. These findings suggest a mechanism by which CCs improve the outcome of AIDS patients with PCP. PMID- 8365284 TI - A randomized comparison of once-monthly or twice-monthly high-dose aerosolized pentamidine prophylaxis. AB - RESULTS: Ten of the 146 (7 percent) evaluable subjects developed PCP during the year study period, and there was no difference in the efficacy of the two regimens. Among patients receiving secondary prophylaxis, the attack rate of PCP at 1 year was 11 percent. This compares favorably with a 1-year attack rate of 19 percent in similar patients receiving standard dose (300 mg) prophylaxis and suggests, but does not prove, a dose-response effect. Concentrations of pentamidine in BAL fluid were not significantly different among the three lobes of the lung. Intrapulmonary pentamidine did not accumulate during the year of study. Aerosolized pentamidine was associated with a marginal but statistically significant increase in the residual volume, decreased flow rates, and increased airway reactivity. OBJECTIVE: The optimal regimen of aerosolized pentamidine in unknown. Published data suggest that there is a dose-response effect and that the occurrence of Pneumocystis carinii pneumonia (PCP) has been associated with prolongation of the interval between doses. The purpose of this study was to compare the efficacy, pharmacokinetics, and physiologic effects of two high-dose regimens of aerosolized pentamidine prophylaxis. DESIGN: Prospective, randomized study of 300 mg twice monthly vs 600 mg once monthly during a 1-year observation period. Pentamidine concentrations in plasma and bronchoalveolar lavage (BAL) fluid were measured and serial pulmonary function was measured. SETTING: A large teaching hospital in San Francisco. PATIENTS: One hundred fifty-one adult (age > 18 years) men with human immunodeficiency virus infection. Of 146 evaluable patients, prophylaxis was primary (no prior PCP) in 108 (75 percent) and secondary (one prior episode of PCP) in 38 (25 percent). MEASUREMENTS: Date and diagnosis of PCP, occurrence of drug toxicity, pulmonary function testing, and concentrations of pentamidine in BAL and plasma. CONCLUSIONS: The data suggest, but do not prove, that a dose-response effect has been demonstrated, and that high-dose aerosolized pentamidine may further reduce the attack rate of PCP. These preliminary observations should be confirmed in a double-blind trial comparing 300 mg with 600 mg administered once monthly. The clinical relevance of the adverse pulmonary effects is unclear and requires further investigation. PMID- 8365286 TI - Mechanical ventilation for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Is the prognosis really improved? AB - The mortality rate among patients with human immunodeficiency virus (HIV) requiring mechanical ventilation (MV) for acute respiratory failure (ARF) secondary to Pneumocystis carinii pneumonia (PCP) is still a matter of discussion. For some authors, it is in the 50 percent range, while for others the prognosis is grim, with virtually no survivors. The aim of this retrospective study conducted between January 1987 and January 1992 was to analyze the outcome of such patients. We studied 33 patients, 29 men and 4 women (38.6 +/- 9.9 years, 21 homosexuals, 8 intravenous drug users, 3 transfusion related, 1 heterosexual) infected by HIV for at least 19.7 +/- 21.6 months. It was the first PCP episode in all but 2 patients and the diagnosis was made by bronchoalveolar lavage (n = 32) or lung biopsy specimen (n = 1). Only three patients were receiving primary prophylaxis for PCP (trimethoprim-sulfamethoxazole [TMP-SMZ], n = 2; pentamidine, n = 1). Pneumocystis carinii pneumonia was the first manifestation of AIDS in nine patients. The duration of symptoms prior to treatment was 19.6 +/- 11.3 days. At the time of hospital admission, laboratory findings were as follows: PaO2 = 40.7 +/- 7.8 mm Hg on room air; serum LDH = 1,172 +/- 792 IU/L; T4 cell count = 60.2 +/- 67/mm3. Mechanical ventilation was always required for ARF, which was never induced by bronchoscopy. The interval between treatment and MV was 8.1 +/- 6.5 days and the duration of MV was 11.4 +/- 9.9 days. The patients were classified into 3 groups on the basis of the duration and type of treatment before MV, as follows: group 1, n = 10: TMP-SMZ (20-100 mg/kg) IV and methylprednisolone (MP) < 5 days before MV; group 2, n = 4: TMP-SMZ > or = 5 days and MP < 5 days; group 3, n = 19: TMP-SMZ and MP > or = 5 days before MV. (The MP dose was as follows: 240 mg/d once a day from day 1 to day 3; 120 mg/d from day 4 to day 6; and 60 mg/d from day 7 to day 9.) Despite MV, TMP-SMZ, and MP, death secondary to PCP-related ARF occurred in 81.9 percent of patients, 20 +/- 4.8 days after the beginning of treatment and 11.4 +/- 9.9 days after the beginning of MV. Six patients survived, five in group 1 and one in group 3.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8365287 TI - Nasal continuous positive airway pressure in decompensated hypercapnic respiratory failure as a complication of sleep apnea. AB - Cardiopulmonary failure resulting from progression of obstructive sleep apnea (OSA) is treated with endotracheal intubation and mechanical ventilation. This study was conducted to determine whether the use of nasal continuous positive airway pressure (CPAP) would rapidly reverse changes in mental status and hypercapnic acidosis in such patients with decompensated hypercapnic respiratory failure resulting from OSA. Six morbidly obese patients (mean weight, 159 +/- 19 kg) were treated with nasal CPAP and supplemental oxygen. Within 24 h of this treatment, there was a significant increase in pH, from a baseline mean of 7.23 +/- 0.03 to 7.35 +/- 0.01 (p < 0.01), and the mean PaCO2 fell from 80 +/- 4 mm Hg to 64 +/- 4 mm Hg (p < 0.01). In addition, there was a dramatic improvement in mental status within 24 h of therapy with nasal CPAP. None of the patients required intubation and mechanical ventilation. There were no complications attributable to the CPAP delivered by nasal mask. We conclude that CPAP delivered by nasal mask can be safe and effective in rapidly reversing changes in mental status and hypercapnic acidosis in this group of patients with severe respiratory failure, and nasal CPAP obviates the need for endotracheal intubation and mechanical ventilation. PMID- 8365288 TI - The association between hypertension and sleep apnea in obese patients. AB - Strong associations have been demonstrated between hypertension (HTN) and obesity, and obesity and sleep apnea (SA). However, it is unclear whether previously suggested relationships between HTN and SA were based on causal mechanisms, or rather, were confounded by obesity. To investigate whether SA may be an independent predictor of HTN, we measured respiration during sleep and BP in 19 participants in a hospital-based weight control program. Additionally, subjects underwent cephalometry, measurement of weight and hip circumferences, and pulmonary function tests. Studies were repeated in 14 subjects following weight loss. Subjects consisted of 9 men and 10 women, ages 43 +/- 11 years (mean +/- SD), and weight of 114 +/- 20 kg. Hypertension (diastolic BP > 95 mm Hg, systolic BP > 160 mm Hg, or a report of current use of an antihypertensive medication) was present in 6 (32 percent) subjects. Sleep apnea was more prevalent among the hypertensive (5/6; 83 percent) than normotensive (2/13; 15 percent) subjects (p < 0.01); respiratory disturbance index (RDI) was 42.4 +/- 16.0 vs 6.2 +/- 2.3 (p < 0.01) in these groups. Compared with normotensive subjects, hypertensive subjects were of similar weight, but had greater central obesity and had lower levels of vital capacity. Regression analyses demonstrated that RDI was the strongest independent predictor of BP level, accounting for approximately 60 percent of the variability in this measurement. Following weight loss, BP and RDI both significantly declined, soft palate width decreased, and vital capacity increased. Thus, in this group of obese subjects, BP level was associated most significantly with the magnitude of sleep-related respiratory disturbances. The obese subjects who are most likely to have SA and HTN are male and/or subjects with greater central obesity and lower vital capacity. PMID- 8365289 TI - A cause of excessive daytime sleepiness. The upper airway resistance syndrome. AB - Subjects with isolated complaints of chronic daytime sleepiness are usually classified as "idiopathic hypersomniacs" and treated symptomatically. A group of these subjects was investigated during nocturnal sleep and daytime naps. In a subgroup of them, sleep was fragmented by very short alpha EEG arousals throughout the sleeping period. These short arousals are usually ignored in sleep analyses, but their impact is significant (in the 15 subjects identified with the syndrome, the mean sleep latency in multiple sleep latency tests was 5.1 +/- 1 min). These arousals are directly related to an abnormal increase in respiratory efforts during sleep (the mean peak inspiratory esophageal pressure measured in our subjects in the respiratory cycle just preceding a transient arousal was -33 +/- 7 cm H2O). Typically, an arousal occurs within one to three breaths of flow limitation associated with abrupt but limited reduction in tidal volume (ie, abnormal increase in upper airway resistance during sleep). The arousal restores normal breathing. Snoring was noted in association with these transient arousals in 10 of the 15 subjects; however, snoring was neither sufficient nor necessary for the identification of the clinical syndrome. Both sexes were equally represented in the affected group. All studied subjects had upper airway anatomy that was mildly abnormal. Nasal continuous positive airway pressure, used as an experimental tool, eliminated the daytime sleepiness (multiple sleep latency mean score = 13.5 min), the transient arousals (mean alpha EEG arousal index decreased from 31.3 +/- 12.4 to 8 +/- 2 per hour of sleep), and the abnormal upper airway resistance. Chronic daytime sleepiness is a major cause of social, economic, and medical impairment. Recognition of this syndrome and its cause is important, as specific treatments can be developed to eliminate the problem. PMID- 8365290 TI - Preflight medical screenings of patients. Analysis of health and flight characteristics. AB - We evaluated the demographic, medical, and flight characteristics of 1,115 passengers who were routinely referred for preflight medical screening by a major domestic air carrier. The largest category consisted of 892 patients who requested in-flight oxygen therapy for cardiopulmonary conditions, of which COPD and cardiac disorders were the most frequent indications; 561 of these patients were 60 years or older. Overall, 386 passengers were recently hospitalized, 911 were using medications, 657 were receiving oxygen therapy, and 761 had flown previously. In the group using in-flight oxygen therapy, the average flight duration was 236 min and layover time, 87 min. These findings indicate that large numbers of patients undergoing preflight screening are receiving medication and have a wide range of medical diagnoses and variable health status. We conclude that preflight medical screening and counselling can be important and helpful in assuring safe and comfortable air travel in this patient population. PMID- 8365291 TI - Relationship between presentation of sarcoidosis and T lymphocyte profile. A study in bronchoalveolar lavage fluid. AB - One hundred patients with histologically verified sarcoidosis were studied. They were divided into three groups, based on their clinical presentation and smoking status. Group A consisted of patients whose disease was detected by routine chest x-ray film, without symptoms; group B included those with respiratory and general constitutional symptoms; and group C included patients with erythema nodosum and/or arthralgia and hilar lymphadenopathy. Group A showed an increased CD4/CD8 ratio of 4.7 +/- 1.1; group B, 8.0 +/- 1.2; and group C counted for the highest ratio of 10.7 +/- 1.5. Cigarette smoking modifies the immunologic bronchoalveolar lavage (BAL) fluid sample profile, since alveolitis was less pronounced in smokers. In addition, BAL fluid samples obtained from sarcoidosis patients with hilar lymphadenopathy showed the most characteristic features of alveolitis, suggesting a disseminated instead of a local immune response. Therefore, the clinical presentation of sarcoidosis and the smoking status of a sarcoidosis patient are crucial for interpreting individual lavage analysis results. PMID- 8365292 TI - Circadian variation of bronchial caliber and antigen-induced late asthmatic response. AB - To study whether circadian variation of bronchial caliber participates in causing late asthmatic response (LAR), house-dust inhalation was made at 10 AM and 6 PM on separate days in 6 house-dust-sensitive asthmatic children aged 8 to 13 years. Bronchial obstruction was assessed through measurements of FEV1 at 4-h intervals from 24 h before to 24 h after the inhalation. The LAR, which is a 15 percent or greater decrease in FEV1 from the value at the same hour of the previous day, occurred 4 h or later after the inhalation in all challenges. The mean (+/- SD) time to the occurrence of the lowest FEV1 (maximum LAR) following the morning inhalation was 14.7 +/- 2.1 h versus 10.0 +/- 2.2 h following the evening inhalation (p < 0.05). Regardless of the hour of inhalation, FEV1 after the inhalation was lowest or near-lowest at 2 AM in all. Therefore, the maximum LAR was indistinguishable from the trough of further amplified circadian variation in FEV1 following the inhalation. These findings suggest that the downward arm of circadian variation may partially participate in causing the LAR. PMID- 8365293 TI - No increase in plasma histamine during PAF-induced airway obstruction in allergic asthmatics. AB - To investigate the possible role of mast cell or basophil histamine release in mediating platelet-activating factor (PAF) airway obstruction, we studied the effect of inhaled PAF (30 micrograms, single dose) on plasma histamine, bronchial caliber, and leukocyte and platelet counts in six patients with mild or moderate allergic asthma (mean age, 27 +/- 1.3 years; mean FEV1, 95 +/- 5 percent of predicted; mean PC20 methacholine, 1.46 +/- 0.36 mg/ml). Specific conductance (SGaw) FEV1, FEF25-75 percent, differential leukocyte and platelet counts, and plasma histamine (radioimmunoassay) were measured before and 5, 10, 15, and 20 min after PAF inhalation. Mean basal plasma histamine level was 0.28 +/- 0.04 ng/ml. Inhalation of PAF caused a fall in SGaw peaking at 5 min (43 +/- 9 percent) and a fall in FEV1 and FEF25-75 peaking at 10 min (19 +/- 10 percent and 30 +/- 13 percent, respectively). There was also a rapid and transient fall in circulating neutrophils at 5 min (from 3,096 +/- 204/mm3 to 2,551 +/- 158/mm3, p < 0.05) followed by a rebound neutrophilia. In contrast, plasma histamine level did not change significantly at any time measured. Conversely in the same asthmatics, a rapid rise in plasma histamine level (from 0.29 +/- 0.03 ng/ml at baseline to 0.53 +/- 0.06 ng/ml at 5 min; p < 0.01) was observed after an allergenic challenge (Dermatophagoides pteronyssinus) causing a fall in FEV1 peaking at 10 min (22 +/- 4 percent). Thus, inhaled PAF may induce airway obstruction and neutropenia in asthmatics without any significant change of plasma histamine level. These results indicate that it is unlikely that lung mast cells or basophils degranulate during PAF-induced bronchoconstriction. PMID- 8365294 TI - Occurrence of occupational asthma. AB - To estimate the percentage of adult asthmatics with occupational asthma in Michigan, a sample of 94 patients, aged 20 to 65 years, who were discharged from one of three Michigan hospitals in 1990 with the primary diagnosis of asthma were interviewed. The patients were classified using the National Institute for Occupational Safety and Health (NIOSH) criteria as having either probable occupational asthma, possible occupational asthma, or not having occupational asthma. Three percent of the adult asthmatics interviewed met the criteria for having probable occupational asthma. One patient from each hospital had probable occupational asthma. Fifteen of 60 patients (25 percent) from hospital A, 3 of 25 patients (12 percent) from hospital B, and 2 of the 9 patients (22 percent) from hospital C had probable or possible occupational asthma. After adjusting for the difference in response rate among patients from the three hospitals, the percentage of adult asthmatics in Michigan whose asthma is caused by work exposure is estimated to be between 3 percent and 20.2 percent. In contrast, 25.5 percent of the patients stated their asthma was caused by bad working conditions. If these percentages were generalizable to the whole state, then according to our survey 330 to 2,222 or by self-reports of the patients, 2,800 of the 11,000 hospital discharges per year in Michigan for asthma among adults could be attributed to a work exposure. PMID- 8365295 TI - Clinical and socioeconomic features of subjects with red cedar asthma. A follow up study. AB - A follow-up study of 128 subjects with red cedar asthma was conducted to evaluate the clinical and socioeconomic impact of the disease in determining the working status of the subjects after the diagnosis was made. The results suggest that the severity of asthma is not the main determinant of working status. Comparing the data at diagnosis and at follow-up examination, we found that the persistence of exposure resulted in a deterioration in the asthma despite the use of more medications. Subjects who were working were younger and had a larger number of dependents than the subjects who were not working at the time of the follow-up examination. We conclude that the socioeconomic factors are important in determining the working status of subjects with red cedar asthma. To prevent severe impairment and disability, there should be more economic incentives for these subjects to choose other jobs. PMID- 8365296 TI - The effects of inhalation of grain dust extract and endotoxin on upper and lower airways. AB - To characterize the short-term effects of grain dusts on pulmonary function, mucosal inflammation, and systemic responses, four women and three men inhaled nebulized corn and soybean dust extracts, endotoxin diluted with Hanks' balanced salt solution (HBSS), and HBSS. Subjects were volunteers recruited via newspaper advertisement and were required to be healthy, nonasthmatic, nonatopic never smokers. The mean age was 26.9 years (range, 19 to 36 years). Using a randomized, double-blind, crossover design, each subject was challenged with each of the 4 substances with at least 10 days between challenges. Serial spirometry, peripheral blood leukocyte and differential cell counts, and 24-h postchallenge nasal lavages were performed. Extracts were produced by mixing 3 g of the corn or soybean dust with 30 ml HBSS followed by shaking for 60 min, centrifugation, then filter sterilization. The endotoxin solution was produced by mixing lyophilized Escherichia coli endotoxin (serotype 0111:B4) with HBSS to attain a final concentration of 7 mg/L, which was the same as the concentration of endotoxin in both grain dust solutions. The pH of all solutions and unmixed HBSS was adjusted to 5.8, which was the native pH of the soybean dust extract. Subjects were challenged with 0.08 ml/kg of each substance, resulting in a range of endotoxin doses of 30 to 60 micrograms, similar to that which a worker might inhale over the course of one workshift. The lowest mean percentage baseline FEV1 (+/- SD) after inhalation challenge was 99.2 +/- 2.1 for HBSS, and it was significantly lower for endotoxin (90.1 +/- 8.5, p = 0.03), corn dust extract (93.1 +/- 4.3, p = 0.02), and soybean dust extract (96.2 +/- 3.7, p = 0.03). In addition, a peripheral blood leukocytosis developed after exposure to all three endotoxin containing solutions (p < 0.05), yet a lower peripheral blood lymphocyte count was found only after inhalation of corn dust extract (p = 0.02). Interestingly, this was associated with a higher nasal lavage lymphocyte count after inhalation of corn dust extract (p = 0.03). Neither the decrease in peripheral blood lymphocytes nor the increase in nasal lymphocytes were found after inhalation of soybean dust extract or endotoxin. Our results indicate that extracts of grain dusts have physiologic effects similar to endotoxin. However, in spite of the same endotoxin levels, the effects of corn dust extract appear to have different biologic activity than either soybean dust extract or endotoxin. PMID- 8365297 TI - Magnesium bolus or infusion fails to improve expiratory flow in acute asthma exacerbations. AB - HYPOTHESIS: Intravenous magnesium sulfate improves objective measures of expiratory flow in patients with acute severe exacerbations of asthma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Urban emergency department. PARTICIPANTS: Forty-eight asthmatic patients aged 18 to 60 years with initial peak expiratory flow rate (PEFR) < 200 L/min who failed to double their initial PEFR after two standardized albuterol treatments. INTERVENTIONS: Subjects were randomized to three groups: a loading dose of magnesium sulfate, 2 g IV over 20 min followed by 2 g/h over 4 h (infusion), magnesium sulfate, 2 g over 20 min followed by placebo infusion (bolus), or placebo loading dose and infusion (placebo). All subjects received standardized aminophylline and steroid therapy. MEASUREMENTS: The PEFR and FEV1 were measured at the start of the loading dose, and 20, 50, 80, 140, 200, and 260 min later using a water-displacement spirometer. Changes from baseline were compared by one-way analysis of variance for repeated measures. RESULTS: Magnesium sulfate administration did not at any time significantly improve either FEV1 (F = 0.036, p = 0.96) or PEFR (F = 0.51, p = 0.61). This study had the power to detect a PEFR difference of 26 L/min and a FEV1 difference of 0.19 L between groups (beta = 0.20, alpha = 0.05 two-tailed significance). CONCLUSION: Use of IV magnesium sulfate in addition to standard therapy does not provide clinically meaningful improvement of objective measures of expiratory flow in patients with moderate to severe asthma exacerbations. PMID- 8365298 TI - A comparison of albuterol administered by metered dose inhaler (and holding chamber) or wet nebulizer in acute asthma. AB - BACKGROUND: Comparative studies of albuterol by wet nebulizer or metered dose inhaler have tested fixed doses of medications. We compared the dose-response relationship to albuterol by wet nebulization or metered dose inhaler in acute asthma. METHODS: Randomized, double-blind, placebo-controlled trial. Patients with acute asthma received either albuterol, 0.4 mg, by metered dose inhaler (and holding chamber) or albuterol, 2.5 mg, by wet nebulizer every 30 min until maximal bronchodilation. Forty patients (forced expiratory volume in 1 s [FEV1]: 1.15 +/- 0.43 L; 36 +/- 12 percent predicted) received metered dose inhaler and 40 others (FEV1: 1.08 +/- 0.52 L; 35 +/- 16 percent predicted) received wet nebulization. RESULTS: Twenty-six patients (65 percent) receiving metered dose inhaler and 30 (75 percent) receiving wet nebulization achieved maximal bronchodilation after two doses. Almost all reached maximal bronchodilation by four doses. The FEV1 improved by 0.72 +/- 0.49 L for metered dose inhaler and 0.68 +/- 0.61 L for wet nebulizer (p = 0.71). A significant linear relationship was seen in both groups (metered dose inhaler r = 0.94; wet nebulizer r = 0.98) between the log dose of albuterol and change in FEV1. About 1/6 the wet nebulizer dose of albuterol was needed to achieve similar response to the metered dose inhaler. CONCLUSIONS: Albuterol by metered dose inhaler provided similar bronchodilation to that achieved by wet nebulization in patients with acute asthma. The cumulative dose-response technique is applicable in the emergency department setting and is helpful in comparing the relative utility of various bronchodilator regimens. PMID- 8365299 TI - The effect of high doses of inhaled salbutamol and ipratropium bromide in patients with stable cystic fibrosis. AB - The effect of large doses of salbutamol (S) and ipratropium bromide (IB) were tested in a double-blind, randomized, crossover study. Nine patients with cystic fibrosis (CF), aged 12.8 +/- 2 years (mean +/- SE), were studied for 8 h on 2 separate days. Pulmonary function tests (PFTs) included spirometry (FEV1), lung volumes (FRC), and airway resistance (Raw) measured by body plethysmography. Heart rate (HR) and oxygen saturation (SaO2) were measured before each test. On 1 day patients received S 200 micrograms, S 400 micrograms, and IB 80 micrograms, by inhalation at 45-min interval (sequence A). On the other day, the sequence was IB 80 micrograms, S 200 micrograms, and S 400 micrograms (sequence B). The PFTs were obtained at baseline, 45 min after each inhalation, and 4 and 8 h after baseline measurements. Baseline PFTs (mean +/- SE) were not significantly different on the 2 study days (FEV1, 1.48 +/- 0.1 vs 1.42 +/- 0.1 L; FRC, 2.77 +/ 0.6 vs 2.87 +/- 0.6 L; Raw, 4.04 +/- 0.2 vs 4.00 +/- 0.3 cm H2O/L/s). The FEV1 and Raw improved from baseline after each inhalation, and at 4 and 8 h during both days (p < 0.05). Forty-five minutes after S 200 micrograms, plus S 400 micrograms, FEV1, FRC, and Raw were not significantly different compared with the values 45 min after IB 80 micrograms, plus S 200 micrograms (1.67 +/- 0.1 vs 1.63 +/- 0.1 L; 2.81 +/- 0.6 vs 2.65 +/- 0.5 L; and 2.98 +/- 0.2 vs 2.66 +/- 0.1 cm H2O/L/s, respectively). The PFTs were not significantly different after maximal doses of IB (80 micrograms) compared with S (600 micrograms). The HR and SaO2 were not significantly different from baseline throughout the study period. These results indicate that both single and sequential therapy have a similar acute bronchodilator effect provided that large doses are used. We speculate that adrenergic and muscarinic pathways are equally important in airflow obstruction in patients with CF. PMID- 8365300 TI - Severe COPD and acute respiratory failure. Correlates for survival at the time of tracheal intubation. AB - The recognition of a reversible cause for acute respiratory failure (ARF) is frequently difficult in patients with severe chronic obstructive pulmonary disease (COPD). We sought to identify clinical findings present at the time of tracheal intubation that were associated with successful weaning and short-term survival among a population of male veterans with severe COPD. Over a 5-year period (1987 to 1991), 39 episodes of ARF requiring mechanical ventilation (MV) were identified in 33 men with severe COPD. All the patients had a baseline FEV1 < 1 L. Univariate analysis suggested a higher serum albumin level and absence of pulmonary infiltrates on chest radiography distinguished survivors (weaned from MV for 72 h) from nonsurvivors (died while undergoing MV or within 72 h of weaning). Multivariate analysis revealed the absence of pulmonary infiltrates on initial chest radiography was the strongest correlate for survival. To examine the significance of these correlates in ARF complicating milder COPD, 19 patients with lesser degrees of chronic airways obstruction and ARF were also studied. Unlike patients with severe COPD, the presence or absence of pulmonary infiltrates on chest radiography was not correlated with survival in patients with milder chronic airways obstruction. Analyzing all COPD patients with ARF, the mortality risk associated with the presence of pulmonary infiltrates on chest radiography increased dramatically with declining baseline lung function. Mortality risk ratio analysis revealed the greatest likelihood for survival was predicted by a higher baseline FEV1 and the absence of pulmonary infiltrates on chest radiography. The extent of baseline airways obstruction alone was not correlated with short-term survival in either group. These observations suggest that in the subset of patients with severe COPD and ARF, the presence of pulmonary infiltrates on chest radiography at the time of tracheal intubation may be associated with less likelihood for survival. An exacerbation of COPD may infrequently be the terminal illness in these patients. PMID- 8365301 TI - Usefulness of transesophageal echocardiography in the treatment of critically ill patients. AB - To evaluate the usefulness of transesophageal echocardiography (TEE) in the treatment of critically ill patients, 80 patients (51 male and 29 female; mean age, 53 years) undergoing both transthoracic echocardiography (TTE) and TEE were studied in a 2-year period. Of these, 48 patients were studied in the ICU, while the other 32 patients were directly referred from the emergency departments. Indications for the study included suspected aortic dissection (34 patients), hemodynamic instability (22 patients), suspected cardiac source of embolism (11 patients), evaluation of the severity of mitral regurgitation (7 patients), and suspected infective endocarditis (6 patients). The probe was passed successfully in 78 of 80 attempts (98 percent). No significant complications were recorded during the transesophageal echocardiographic study. Transesophageal echocardiography provided critical information that was not obtained by TTE in 39 of 78 studies (50 percent, p < 0.005). Cardiac surgery was prompted by TEE findings in 14 patients (18 percent) and these findings were all confirmed at operation. Transesophageal echocardiography was a safe, well-tolerated, and valuable diagnostic approach for the rapid detection of specific cardiac abnormalities in patients with critical illness; TEE should be considered in the treatment of critically ill patients especially when TTE provided inadequate information. PMID- 8365302 TI - The addition of sighs during pressure support ventilation. Is there a benefit? AB - The purpose of this study was to determine if sigh breaths delivered during pressure support ventilation (PSV) were beneficial in maintaining arterial oxygenation (PaO2) and pulmonary mechanics. Ten patients being weaned from mechanical ventilation in the PSV mode were studied. All patients were ventilated for 4 h without sighs, 4 h with sighs, and again for 4 h without sighs. During each 4-h period, continuous measurements of ventilatory volumes and airway pressures were accomplished. At the end of each 4-h period, an arterial blood gas determination was obtained. There were no statistically significant differences in any of the measured variables during the different periods of ventilation. We conclude that the sigh breath is of no benefit during PSV. PMID- 8365304 TI - Closure of an intermediate care unit. Impact on critical care utilization. AB - We studied the effect of closing a six-bed intermediate care area (ICA) on utilization of a multidisciplinary critical care unit (CCU). Data were collected on all admissions to the 7-bed CCU for 9 months prior to ICA closure (n = 217) and compared with 9 months after CCU expansion (7 to 9 beds) and ICA closure (n = 407). Nonemergency CCU admissions increased from 41 to 112 after ICA closure (p < 0.03). Mean APACHE II score within 24 h of admission decreased from 21.9 +/- 7.4 to 18.6 +/- 7.4 (p < 0.0001). The proportion of patients with APACHE II score < 15, increased from 30/217 to 136/407 accounting for an increase from 5.4 percent to 12.7 percent of CCU days (p < 0.0001). Nursing workload at the time of discharge from CCU decreased (p < 0.0001). The ICA closure altered CCU admission and discharge decision-making. "Low-risk" admissions increased and patients remained in the CCU until they required less nursing care. One factor determining utilization of a CCU is the facilities available outside the unit. A CCU management system is especially important when a wide range of illness severity is present. PMID- 8365303 TI - Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome. AB - To assess the cardiorespiratory effects of pressure-controlled ventilation (PCV) and pressure-controlled inverse ratio ventilation (PC-IRV), we compared pressure controlled ventilation with an inspiratory-to-expiratory time ratio (I/E) of 1/2 (PCV) and of 2/1 (PC-IRV) to volume-controlled ventilation (VCV) with an I/E of 1/2 in 10 patients suffering from the adult respiratory distress syndrome. In all modes, the inspiratory oxygen fraction, tidal volume, respiratory rate, and total positive end-expiratory pressure (PEEPt = applied PEEP + intrinsic PEEP) were kept constant. Each ventilatory mode was applied for 1 h in a randomized order. No significant differences in PaO2 were observed among the three modes. The PaCO2 was lower (p < 0.05) in PC-IRV (39 +/- 4 mm Hg) than in PCV (43 +/- 5 mm Hg) and in VCV (45 +/- 5 mm Hg). The peak airway pressure was significantly lower in PC IRV than in PCV (p < 0.05) and in PCV than in VCV (p < 0.05), but plateau pressure was not different in the 3 modes. The mean airway pressure (mPaw) was significantly higher (p < 0.05) in PC-IRV (21.4 +/- 0.7 cm H2O) than in PCV (17.1 +/- 0.7 cm H2O) and VCV (16.4 +/- 0.5 cm H2O). As a consequence of this increased mPaw, PC-IRV induced a decrease in cardiac index (CI) (3.3 +/- 0.2 vs 3.7 +/- 0.2 L/min/m2 in VCV; p < 0.05) and hence in oxygen delivery (DO2) (424 +/- 28 vs 469 +/- 38 ml/min/m2 in VCV; p < 0.05). Our results suggest that neither PCV nor PC IRV bring any benefit over VCV in terms of arterial oxygenation. Moreover, the increase in mPaw induced by PC-IRV may be deleterious to the CI and DO2. PMID- 8365305 TI - Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. AB - BACKGROUND: Septic shock is frequently complicated by a syndrome of disseminated intravascular coagulation (DIC). Numerous uncontrolled clinical studies have reported that antithrombin III (ATIII) substitution might prevent DIC and death in septic shock. METHODS: We conducted a randomized double-blind placebo controlled trial in patients with a documented septic shock and DIC. The patients received either a placebo or ATIII (90 to 120 IU/kg in loading dose, then 90 to 120 IU/kg/d during 4 days). Administration of fresh frozen plasma, platelets, and fibrinogen concentrates was restricted to patients with hemorrhages and severe decreases in prothrombin time, platelet count, and fibrinogen levels. RESULTS: Thirty-five patients entered the study (18 placebo, 17 ATIII). Both groups were well balanced for all demographic, hemodynamic, and biologic data. Three patients were excluded before the treatment allocation code was broken. In the ATIII group, ATIII levels were rapidly corrected and remained over normal levels until day 10; sequential protein C and protein S levels were not modified. The duration of DIC was significantly reduced: in the ATIII group, 64 percent of patients were cured of DIC at day 2, and 71 percent were cured at the end of treatment vs in the placebo group, 11 percent (p < 0.01) and 33 percent (p < 0.05), respectively. In the 32 included patients, the mortality in ICU was reduced by 44 percent in the ATIII group (p = 0.22, NS). Care loads and transfusion requirements were not different. No side effect was observed. CONCLUSIONS: Mortality was reduced by 44 percent in this trial, but the difference did not reach the statistical significance. Circulating protein C and protein S levels were not modified by ATIII supplementation. High doses of ATIII concentrates significantly improved sepsis-induced DIC during septic shock. The trend toward improved survival suggests further randomized studies. PMID- 8365306 TI - Extracorporeal carbon dioxide removal and low-frequency positive-pressure ventilation. Improvement in arterial oxygenation with reduction of risk of pulmonary barotrauma in patients with adult respiratory distress syndrome. AB - Mortality of the adult respiratory distress syndrome (ARDS) remains high and could be increased by pulmonary barotrauma induced by positive-pressure mechanical ventilation. Extracorporeal CO2 removal combined with low-frequency positive-pressure ventilation (ECCO2R-LFPPV) has been proposed to reduce lung injury while supporting respiratory failure. Use of this technique in 23 patients resulted in the following: a dramatic and highly significant increase of PaO2 obtained rapidly with ECCO2R-LFPPV, allowing subsequent reduction in inspired oxygen fraction; a reduction of the risk of barotrauma evidenced by a significant decrease in pressures and insufflated volumes; a survival rate of 50 percent. Bleeding was the only complication related to the technique and was the cause of death in four patients. This method allowed improvement in gas exchange along with reduction of the risk of barotrauma caused by the ventilator. PMID- 8365307 TI - Hypoxemic episodes of patients in a postanesthesia care unit. AB - The incidence, degree, and duration of acute hypoxemia were evaluated with continuous arterial hemoglobin oxygen saturation monitoring by pulse oximetry in 100 postoperative patients during 40 percent oxygen administration by aerosol face tent from postanesthetic recovery room admission to discharge. Saturations were recorded by pulse oximeters (Nellcor-N 200) with desaturations of < or = 92 percent for > or = 30 s considered significant. On recovery room admission, 15 percent of patients were experiencing episodes of desaturation. Low admission saturations correlated positively with patient age and body weight, American Society of Anesthesiologists class, patients having received general anesthesia, and with greater volumes of intraoperative intravenous fluids, particularly > 1,500 ml. Later desaturations to 86.7 +/- 4.6 percent (72 to 91 percent) at 32 +/ 54 min after admission for 5.2 +/- 12.6 min occurred in 25 percent of patients and correlated positively with peripheral surgical procedures, low oxygen saturation on admission, duration of anesthesia, and volume of intraoperative intravenous fluids. Desaturation durations were longer for female subjects and correlated positively with body weight and intravenous fluid volume. Significant arterial hemoglobin oxygen desaturations occurred despite prophylactic oxygen administration by aerosol face tent during short-term postoperative recovery room care. PMID- 8365308 TI - Pressure-preset ventilation. Part 2: Mechanics and safety. PMID- 8365309 TI - The pathophysiologic changes following bile aspiration in a porcine lung model. AB - Aspiration of bile is an underpublicized aspiration syndrome. Using a porcine lung model, the physiologic response and the histopathology of lung tissue were evaluated after the intratracheal instillation of sublethal doses of bile. Twenty one domestic swine (11 to 19 kg) were the studied population. Three groups of five swine were evaluated: a control group received intratracheal physiologic saline (pH 7.45); study group 1 received strained gastric contents (pH 2.24); and study group 2 received strained bile (pH 7.19). All animals received the solutions at 0.5 ml/kg intratracheally. Lungs of six additional animals were studied (two gastric, two bile, and two physiologic saline) after aspiration by scanning electron microscopy (SEM). A seventh untreated animal was used as the SEM control. The physiologic data were analyzed using analysis of variance for repeated measures. The SEM and histopathologic results were graded by an observer blinded to the groups and were analyzed using the analysis of variance (ANOVA) and Scheffe tests. The group with bile aspiration was consistently characterized by significant deterioration of PaO2, the alveolar-arterial (A-a) gradient, shunt fraction, and static compliance (p < 0.01); and the light histopathologic and SEM findings demonstrated pathologic changes in the bile-exposed lung (p < 0.05) greater than the gastric- or saline-exposed lungs. It is concluded that bile aspiration produces a severe chemical pneumonitis leading to noncardiac pulmonary edema. PMID- 8365310 TI - Increasing back pain in a young man. PMID- 8365311 TI - Diffuse pulmonary infiltrates and respiratory failure following 2 weeks of dyspnea in a 45-year-old woman. PMID- 8365312 TI - Measurement of oxygen consumption after uncomplicated acute myocardial infarction. AB - BACKGROUND: Oxygen consumption (VO2) has been shown to be decreased after acute myocardial infarction (AMI) complicated by cardiogenic shock. STUDY OBJECTIVE: To evaluate early measurement of VO2 by indirect calorimetry after an uncomplicated AMI (UAMI). STUDY DESIGN: Prospective nonrandomized case study. SETTING: Emergency department of a large urban hospital. PARTICIPANTS AND INTERVENTIONS: Twenty-six consecutive patients presenting with confirmed UAMI. VO2 was measured by indirect calorimetry (Deletrac, Datex Ins,) which is noninvasive. All patients received buccal or intravenous nitroglycerin and thrombolytic therapy, and none received opiates before VO2 measurement. RESULTS: Two groups of patients were identified by subsequent development of cardiogenic shock. Group 1 did not develop cardiogenic shock, and group 2 developed shock within 24 h of admission. Group 1 (n = 22) had a significantly higher VO2 compared to group 2 (n = 4), mean 154(SD 25) vs mean 100(SD 13) ml/min.m2, p < 0.002. Group 1 had a significantly higher increase in basal metabolic rate than group 2, mean 30 percent (SD 11) vs mean 10(SD 15) percent, p < 0.007. There was no significant difference in age, heart rate (HR), shock index (SI), or rate-pressure product (RPP) between groups 1 and 2. All patients in group 2 developed cardiogenic shock despite thrombolytic therapy, and two died within 24 h of admission. CONCLUSION: VO2 is increased in UAMI and represents increased metabolic demands of peripheral tissues and not cardiac oxygen uptake. A reduction in VO2 (< 100 ml/min.m2) after AMI may be an early predictor of subsequent development of cardiogenic shock. Measurement of VO2 in UAMI by indirect calorimetry in the emergency department may be of value to identify patients at high risk and could influence their management. PMID- 8365313 TI - Cardiac profiles of national-class race walkers. PMID- 8365314 TI - Redefinition of normal sinus heart rate. PMID- 8365315 TI - Thoracoscopy in the subacute management of patients with thoracoabdominal trauma. PMID- 8365316 TI - Disappearance of a left ventricular aneurysm on radionuclide ventriculography due to formation of a mural thrombus. AB - Radionuclide ventriculography is an accepted method for diagnosing left ventricular aneurysms, but false-negative studies have been associated with a mural thrombus filling the left ventricular cavity. We describe a patient with a left ventricular aneurysm due to myocardial infarction whose aneurysm scintigraphically "disappeared" from serial radionuclide ventriculograms. This was documented echocardiographically and pathologically to be due to the formation of a large mural thrombus. Review of the literature suggests that radionuclide ventriculography and echocardiography may be complementary techniques in the diagnosis of left ventricular aneurysm. Echocardiography may remain diagnostic when a mural thrombus has caused the loss of the characteristic scintigraphic findings on radionuclide ventriculography. PMID- 8365317 TI - Association of miliary lung metastases and bone metastases in bronchogenic carcinoma. AB - Five cases of miliary lung metastasis among 630 patients with bronchogenic carcinoma were investigated. Bone metastases from the bronchogenic carcinoma were observed in 246 (39 percent) of these 630 patients, and the five were all patients in this latter group. These results suggest that bronchogenic carcinoma may produce miliary lung metastasis through its bone metastasis. PMID- 8365318 TI - Toxic shock syndrome as the AIDS-defining diagnosis. AB - Toxic shock syndrome (TSS) has been infrequently reported as a complication of AIDS. We present the case of a 24-year-old man, previously unknown to be positive for the human immunodeficiency virus, presenting in septic shock. The literature on TSS in AIDS is reviewed and the association between the two diseases is presented. PMID- 8365319 TI - Needle/wire lung nodule localization for thoracoscopic resection. AB - Small lung nodules undiagnosed by percutaneous needle biopsy have traditionally gone to thoracotomy for diagnosis. We describe a technique using computed tomographic needle/wire lung localization of these nodules, to be resected using video-assisted thoracoscopy. This is less invasive and less painful than thoracotomy and provides for cost-effective definitive diagnosis. PMID- 8365320 TI - Localized Wegener's granulomatosis relapsing as diffuse massive intra-alveolar hemorrhage. AB - In a 75-year-old patient presenting with a solitary pulmonary mass, a localized form of Wegener's granulomatosis was diagnosed after lobectomy. In the absence of extrapulmonary manifestations and after a benign postoperative course, the patients was discharged without medical treatment. Three months later, diffuse alveolar hemorrhage developed abruptly, necessitating mechanical ventilation, and was followed by cardiac complications and a fatal outcome. This case and another previously reported strongly suggest the need for medical treatment in patients with a localized form of pulmonary Wegener's granulomatosis, even when complete remission after surgical resection of the lung lesion seems to have been achieved. PMID- 8365321 TI - Combined median sternotomy and video-assisted thoracoscopic resection of pulmonary metastases. AB - Median sternotomy has been a common approach for resection of bilateral pulmonary metastases. It provides good exposure and quick accessibility to most lesions in the lung. The retrocardiac left lower lobe may at times be a problematic area for resection of metastases. We have used a simultaneous median sternotomy and left video-assisted thoracoscopic approach to remove three such lesions in two patients, with satisfactory results. PMID- 8365322 TI - Use of Nd:YAG laser in endobronchial granular cell myoblastoma. AB - Granular cell myoblastoma is an uncommon benign tumor that causes pulmonary complications due to obstruction of the airways. We report the first case of bronchial obstruction due to granular cell tumor treated with Nd:YAG laser. The Nd:YAG laser appears to be an effective new tool for relieving obstruction and, in some cases, preventing recurrence, and can be delivered with the use of a flexible bronchoscope. PMID- 8365323 TI - Fluid bronchogram. A common finding in opacified lung requiring contrast medium administration for demonstration. AB - One example was selected to demonstrate the requirement of intravenous administration of contrast medium for visualization of the fluid bronchogram in opacified lung, as is the case in most patients. Another example was chosen to show that on rare occasions, a faint fluid bronchogram could be detected without contrast medium because of marked dilation of the bronchi. The mechanism for the computed tomographic demonstration of the fluid bronchogram and it significance were discussed. PMID- 8365324 TI - Fatal cerebral fat embolism associated with a patent foramen ovale. AB - A healthy 22-year-old woman developed respiratory failure and brain death within 48 h of bilateral tibial fractures. Autopsy showed fat embolism in the lung and brain, and a large patent foramen ovale that may have contributed to massive cerebral fat embolism. PMID- 8365325 TI - Fatal respiratory arrest in adult epiglottitis in the intensive care unit. Implications for airway management. AB - A 64-year-old man with acute epiglottitis, monitored in an ICU without an artificial airway, suffered sudden fatal respiratory arrest 36 h after admission despite rapid emergency interventions. This case demonstrates the importance of adequate airway protection in adult epiglottitis even within an ICU setting. A protocol for airway management for such patients is presented. PMID- 8365326 TI - Acute right ventricular infarction mimicking extensive anterolateral wall injury. AB - A patient presented with an acute right ventricular infarction characterized by an electrocardiographic current of injury in both the inferior (2,3,aVF) and anterior precordial leads (V1-V6). Cardiac catheterization demonstrated normal left ventricular wall motion, a codominant circulation, and severe disease of the right coronary artery. We propose that this coronary anatomy explains the injury currents on the electrocardiogram. This case illustrates a rare presentation of right ventricular myocardial infarction mimicking an extensive anterolateral wall injury. PMID- 8365327 TI - Drug-induced pulmonary edema in a patient infected with human immunodeficiency virus. AB - Adverse reactions to drugs are common in patients infected with the human immunodeficiency virus (HIV). In these patients pulmonary reactions to drugs may be difficult to differentiate from opportunistic pulmonary infections. We report a HIV-infected patient who on two occasions developed acute pulmonary edema related to the administration of ibuprofen. PMID- 8365328 TI - Right atrial mass biopsy guided by transesophageal echocardiography. AB - A 69-year-old woman was found to have a right atrial mass on transthoracic echocardiogram. Biopsy of the mass was performed using transesophageal echocardiography for visual guidance. Pathologic study revealed an organizing thrombus. This case illustrates the clinical utility of transesophageal echocardiography in the biopsy of right atrial masses. PMID- 8365329 TI - Thionyl-chloride-induced lung injury and bronchiolitis obliterans. AB - Thionyl-chloride (TCl) is used in the manufacture of lithium batteries, producing SO2 and HCl fumes on contact with water. We report two cases of accidental TCl exposure resulting in lung injury that may vary from a relatively mild and reversible interstitial lung disease to a severe form of bronchiolitis obliterans causing, after a latent period, an acute/chronic respiratory failure as well as other complications (spontaneous pneumothorax and bronchopleural fistula), previously unreported in TCl fume inhalation. PMID- 8365330 TI - Bronchopulmonary bacillary angiomatosis. AB - A man with prior AIDS developed acute febrile interstitial pneumonitis, hilar and paratracheal adenopathy, and bronchial polyps. The polyps were histologically typical for bacillary angiomatosis and complete symptomatic and radiographic response to oral clarithromycin was seen. The clinical presentation of bacillary angiomatosis includes pulmonary disease and in particular bronchial polyps; clarithromycin is an effective oral antibiotic. PMID- 8365331 TI - Late cardiac strangulation due to an iatrogenic pericardial defect. AB - A 14-year-old boy developed broad posterolateral myocardial infarction. During cardiac surgery at age five, a small pericardial window had been made. Autopsy revealed an extensive left-sided pericardial defect and necrosis of the left ventricular free wall, which had herniated and strangulated through the enlarged pericardial defect. PMID- 8365332 TI - Acute ventilatory failure from massive subcutaneous emphysema. AB - A 66-year-old woman developed massive subcutaneous emphysema following intubation. Acute thoracic restriction developed resulting in life-threatening respiratory acidosis. The patient could not be ventilated with conventional means. A tracheostomy was performed to decompress the chest and mediastinum with rapid resolution following. Although ventilatory failure from subcutaneous emphysema is very unusual, decompression with tracheostomy can be life saving. PMID- 8365333 TI - Hemoptysis during sexual arousal. An unusual manifestation of amyloidosis. AB - Hemoptysis associated with sexual arousal is thought to be secondary to cardiac dysfunction brought on by the physiologic stress of sexual activity. A patient who presented with hemoptysis occurring only during episodes of sexual stimulation was subsequently found to have cardiac amyloidosis. PMID- 8365334 TI - Miliary opacities diagnosed as lung metastases of a thyroid carcinoma after 13 years of stability. AB - A 29-year-old man was hospitalized for the diagnosis of clinically asymptomatic miliary opacities discovered 13 years earlier and unchanged since then. Transbronchial biopsy showed metastatic thyroid carcinoma. Thyroid surgery revealed massive local invasion by a papillary carcinoma. We conclude that thyroid carcinoma, whether clinically detectable or not, should be considered in the diagnostic investigation of stable miliary lesions. PMID- 8365335 TI - Pacemaker-induced friction rub and apical thrill. PMID- 8365336 TI - Pacemaker-induced friction rub and apical thrill. PMID- 8365337 TI - Diagnosis of acute pulmonary embolism in patients with COPD. PMID- 8365338 TI - Adenosine triphosphate enhancement of postischemic function in immature myocardium. PMID- 8365340 TI - Aspiration of potpourri. PMID- 8365339 TI - Evaluation of cardiac output by thoracic electrical bioimpedance during exercise in normal subjects. PMID- 8365341 TI - The atrial natriuretic peptide paradox. A hypothesis. PMID- 8365342 TI - Blunt chest trauma causing isolated single papillary muscle dysfunction and mitral regurgitation. PMID- 8365343 TI - Pulmonary barotrauma in mechanical ventilation. PMID- 8365344 TI - Controlled-release oral salbutamol and cardiac arrhythmias in asthmatic patients. PMID- 8365345 TI - Value of a Mycobacterium avium complex respiratory tract isolate as a predictor of disseminated infection. PMID- 8365346 TI - NIH's "Family Inn" lets out-of-town youngsters stay "home". PMID- 8365347 TI - Mismatch recognition in chromosomal interactions and speciation. AB - Homologous chromosomes interact during meiosis by means of proteins involved in recombination and in the recognition and repair of mismatched base pairs. Recombination proteins bring homologous chromosomes or chromosomal regions together by facilitating the search for DNA homology and by catalyzing strand exchange between homologous molecules or regions. Mismatch recognition and repair proteins act as editors of recombination and appear to disrupt those DNA associations that contain mismatched base pairs. Thus, it may be that, as chromosomes diverge in their primary sequence and become increasingly polymorphic, recombinational interactions leading to chromosome pairing and recombination tend to be inhibited. Decreasing homologous interactions within and between chromosomes will clearly contribute to maintaining the integrity of individual chromosomes and may ultimately lead, as a result of sterile meioses, to the reproductive isolation of closely related species. PMID- 8365348 TI - Sequence organization and evolution, in all extant whalebone whales, of a DNA satellite with terminal chromosome localization. AB - A heavy (GC rich) DNA satellite with terminal chromosomal localization is characteristic for all mysticete (whalebone whale) genomes. Sequences of 58 repeats of the satellite were compared in all ten extant mysticete species. In three families comprising eight species, the typical repeat length was 422 (421) bp. In two species, the northern right whale and the bowhead, of family Balaenidae (right whales) the repeats were much longer, typically ca. 900 and ca. 1200 bp. In all species the repeats were composed of a unique portion of constant length (212/211 bp), and a subrepeat portion, the length of which was variable. The evolutionary rigidity of the unique portion of the repeat is contrasted by the pronounced length variability of the subrepeat portion. The subrepeat portion consists essentially of 6 bp motifs, such that length differences are usually in multiples of 6 bp. The motif TTAGGG constituted 35%-50% of the subrepeats. Comparison between the unique portion of the 58 sequenced repeats revealed that the repeats divided into two primary groups, one comprising the two balaenids, the other including the eight remaining species. The mean difference between the two groups averaged 8.4%. In this sequence comparison the repeats of the pygmy right whale constituted a group that was separated from repeats of the other species. In all other cases repeats were intermingled to some extent between species. Comparison of individual repeats suggests that the unique portion evolves in concert, at a slow rate. A neighbor-joining comparison between the consensuses of all species suggests that the unique portion of the repeats evolves at a somewhat different rate in different lineages. PMID- 8365349 TI - Solitary and synaptonemal complex-associated recombination nodules in pro-nurse cells during oogenesis in Drosophila melanogaster. AB - An oocyte in Drosophila melanogaster originates from 1 of 16 cells comprising an ovarial syncytium. The two pro-oocytes proceed into the pachytene stage of meiosis, but only one develops further into a mature oocyte while the other reverts to a nurse cell. It is known that pro-nurse cells also enter meiosis, as they contain incomplete synaptonemal complexes (SCs). We now show that these cells also harbour recombination nodules (RNs). In cells that only occasionally contain SC segments, the RNs are typically not located close to distinct tripartite SC structures. Instead, these RNs are frequently associated with a spherical body of amorphous material and two to three, more or less parallel fibres, possibly representing SC material. The significance of the solitary RNs is discussed in relation to the present knowledge of the assembly and disassembly of the SC. PMID- 8365350 TI - Yeast pre-meiotic DNA replication utilizes mitotic origin ARS1 independently of CDC7 function. AB - In budding yeast, mitotic DNA replication initiates at sequence-specific replication origins, the prototype for which is ARS1. Initiation serves as the primary control point for mitotic DNA replication, and is catalyzed by the Cdc7 protein kinase. In contrast, premeiotic DNA replication apparently does not require Cdc7, and the existence and nature of specific replication origins in the meiotic division cycle have not been previously reported. We have begun to investigate the mechanism of premeiotic DNA synthesis by determining whether or not ARS1 functions as a DNA replication origin in meiosis. We have taken advantage of the fact that transcription through ARS1 disrupts its ability to function as an origin to show that ARS1 is required for premeiotic DNA replication of a plasmid bearing this element. Further, premeiotic replication from ARS1 still occurs in a cdc7 mutant strain held at conditions non-permissive for Cdc7 protein kinase activity. These findings reveal that premeiotic DNA replication can initiate from origins also used in mitosis, and is not regulated by Cdc7. Taken together with previous findings implicating Cdc7 in meiotic DNA recombination and induced mutagenesis, these findings prompt us to postulate that the Cdc7 protein kinase regulates some step common to several DNA metabolic processes such as local disassembly of chromatin or activation of a key component of the DNA metabolic machinery. PMID- 8365351 TI - Chromatin condensation behaviour of the Y chromosome in the human testis. I. Evidence for decondensation of distal Yq in germ cells prior to puberty with a switch to Sertoli cells in adults. AB - The condensation behaviour of the human Y chromosome in germ cells and Sertoli cells of pre- and post-pubertal testes was followed by fluorescence in situ hybridisation using probes for three different regions of the Y chromosome. Patterns of expansion or contraction of signal are taken to reflect degrees of condensation of the related Y chromatin and hence its potential for genetic activity. For probe pHY2.1, which labels the distal non-fluorescent and fluorescent heterochromatin of the Y chromosome (Yq12), an expanded signal seen in gonocytes of the prepubertal testis is superseded by a condensed signal seen in adult germ cells at all but the zygotene stage of meiotic prophase when meiotic pairing takes place. In contrast, Sertoli cells show a condensed signal pre-pubertally but a greatly expanded signal in the adult testis. A totally condensed pHY2.1 signal is found in a chromosomally normal man with Sertoli-cell only syndrome. It is hypothesised that control over at least some facets of spermatogenesis may not, in the adult, be autonomous to the germ cells, but rather may emanate from the Sertoli cells. Chromatin expansion at zygotene could, however, be important for pairing and crossing over in the XY bivalent, successful synapsis ensuring survival of spermatocytes into the post-meiotic stages. PMID- 8365352 TI - Neurosteroids: 3 alpha-hydroxy-5 alpha-pregnan-20-one and its precursors in the brain, plasma, and steroidogenic glands of male and female rats. AB - A RIA procedure for measuring progesterone (PROG), 5 alpha-pregnane-3,20-dione (5 alpha-DH PROG), and 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH PROG) has been developed and validated by GLC/mass spectrometry. Measurements were made in intact and adrenalectomized (ADX) male rats, in cyclic, pregnant, spayed, and spayed-ADX females, and in both males and spayed females injected with PROG. The predominant contribution of the ovary to the concentrations of 3 alpha,5 alpha-TH PROG in plasma and brain, was indicated by its larger levels in females, in particular during pregnancy, and by its presence in ovarian tissue and disappearance after ovariectomy. An additional adrenal origin in both males and females was shown. Neither PROG nor 5 alpha-DH PROG disappeared from brain, contrary to plasma, after combined adrenalectomy and gonadectomy, thus suggesting that PROG might be synthetized de novo in brain. However, the concentrations of 3 alpha,5 alpha-TH PROG in plasma and brain of female rats were positively correlated with the concentrations of PROG in plasma, indicating that plasma PROG was the major precursor of 3 alpha,5 alpha-TH PROG. The direct formation of 3 alpha,5 alpha-TH PROG from PROG in brain was strongly suggested by the increased 3 alpha,5 alpha-TH PROG/PROG ratios in brain vs. plasma, when measured in control females, and after injection of PROG to both males and OVX females. It was previously reported that 3 alpha,5 alpha-TH PROG is a sedative/anxiolytic steroid, as a result of its binding to gamma-aminobutyric acid (GABA)A receptors and allosteric potentiation of GABAcergic neurotransmission. Its concentrations in brain reach indeed the neuroactive range in cyclic and pregnant females, and are compatible with a physiological role of this neurosteroid. PMID- 8365353 TI - Effects of female hormones and 3,5,3'-triiodothyronine or dexamethasone on induction of epidermal growth factor and proteinases F, D, A, and P in the submandibular glands of hypophysectomized male mice. AB - The effects of progesterone (Pro), 5 alpha-dihydrotestosterone (DHT), 17 beta estradiol (E2), T3, and dexamethasone (Dex), given alone or in combination, on induction of epidermal growth factor (EGF) and proteinase isozymes in the submandibular glands of hypophysectomized mice were examined. Each hormone, except E2, acting alone had essentially comparable inductive effects on EGF concentrations and on total proteinase activity. E2 alone had no inductive effect at all. Pro acted synergistically with T3, but its inductive effect was diminished when given with Dex. E2 was not synergistic with T2, and it inhibited the effect of Dex; it also partially blocked the action of DHT on induction of proteinase activity but not of EGF. Simultaneous administration of all five hormones restored total proteinase activity completely but EGF levels to only 50% of values for intact males, respectively. Submandibular proteinases were resolved by isoelectric focusing into four isozymes: proteinase F (pI 4.8), proteinase D (pI 5.8), proteinase A (pI 6.2), and proteinase P (pI 10.0). Pro alone slightly increased levels of proteinase F but greatly raised levels of the other three isozymes. This inductive action was augmented when Pro was given with T3 but blocked when it was given with Dex. E2 alone not only failed to induce any of the isozymes, but even further reduced levels of proteinase F. It also decreased the inductive effects of T3 on these isozymes, and with Dex completely blocked induction of proteinases D, A, and P. E2 plus DHT suppressed proteinase F levels and only induced proteinase A. All five hormones together reestablished the isozyme profile seen in intact males. These results show that Pro by itself is as capable as androgens, thyroid hormone, or glucocorticoid in regulating expression of these submandibular polypeptides, and that its action can be modulated by other pituitary-dependent hormones. In addition, they demonstrate that E2 does not regulate their expression, and that it has an inhibitory effect on the inductive action of other hormones. Last, they indicate that these various hormones may regulate expression of EGF and of each of the individual proteinase isozymes differently. PMID- 8365354 TI - Induction of prostaglandin endoperoxide synthase isoform-2 in ovine cotyledonary tissues during late gestation. AB - The present study was designed to characterize the developmental pattern of specific prostaglandin endoperoxide synthase (PGS) isoform immunoreactivity and activity in tissues of fetal origin during the last half of gestation in sheep. Fetal amnion, allantochorion, and cotyledons were collected under halothane general anesthesia on days 79-80, 105-108, 120-122, 128-131, and 140-145 (term) of pregnancy. Solubilized extracts were prepared and analyzed by immunoblots using anti-PGS antibodies previously shown to recognize PGS isoform-1 and -2 (PGS 1 and PGS-2). PGS activity from cotyledon microsomes was assayed by the measurement of prostaglandin E2 (PGE2) production under initial velocity conditions. All fetal tissues contained PGS-1 at each of the stages of gestation examined, with minimal regulation of this isoform from 79-144 days gestation. In contrast, PGS-2 increased gradually in the cotyledons from 120-139 days gestation, with the most marked expression observed at term. PGS-2 was not detected in amnion or allantochorion. PGS activity in cotyledons increased (P < 0.01) in parallel with immunoreactive PGS-2 levels; indicating that PGS-2, rather than PGS-1, is associated with increased PG synthesis in this tissue. Both the activity (n = 5/group) and the amount of PGS-2 increased significantly from 105 108 days gestation to term (P < 0.01). We conclude that the increase in PGS that occurs at term in sheep is predominantly active PGS-2 localized to fetal cotyledons. PMID- 8365355 TI - Insulin stimulates endothelin binding and action on cultured vascular smooth muscle cells. AB - Hyperinsulinemia has been implicated as a separate risk factor for the development of accelerated cardiovascular disease, but the mechanism is unknown. Recently, we and several other groups have shown that insulin stimulates the production and secretion of the vasoconstrictor peptide endothelin-1 (ET-1) from vascular endothelial cells, and hyperinsulinemia results in increased plasma ET levels in vivo. However, the interactive effects of diabetes, insulin, and glucose on ET target tissues, like those on vascular smooth muscle cells (VSMC), are not well defined. In these studies, we examined the effects of the diabetic factors on ET receptors and [3H]thymidine incorporation into cultured cells prepared from control, streptozocin-diabetic, insulin-treated diabetic, and hyperinsulinemic rats. Scatchard analysis of saturation binding studies revealed a 2-fold increase in ET receptor number in normal VSMC treated in vitro with insulin, whereas glucose had no significant effect. Neither treatment affected receptor affinity. Similarly, aortic smooth muscle cells, brain capillary pericytes, and kidney afferent arteriolar smooth muscle cells from rats made hyperinsulinemic in vivo each showed approximately a 2-fold increase in receptor number. This increase in receptor density probably resulted from the stimulation of receptor protein production, because insulin caused a maximal 2.3 +/- 0.3 (+/- SEM) fold increase in the ETA receptor mRNA expressed in cultured VSMC by 4 h. Both insulin and ET significantly increased thymidine incorporation in aortic VSMC, but ET-1 was much more potent in this regard. However, the combined effects of insulin plus ET-1 resulted in a 10-fold increase in this index of cell proliferation, significantly different from the effects of either peptide alone. We postulate that hyperinsulinemia in vivo may potentiate ET release and receptor mediated action, thereby contributing to vascular disease in the setting of diabetes. PMID- 8365356 TI - Prostaglandin F2 alpha mediates platelet-activating factor-stimulated atrial natriuretic factor release from the isolated rat heart. AB - Platelet-activating factor (PAF) and the prostaglandins have recently been shown to stimulate atrial natriuretic factor (ANF) secretion from the heart. As PAF also potentiates the release of cyclooxygenase products from isolated hearts, the role of these substances in PAF-induced ANF secretion was investigated. Using an isolated perfused rat heart preparation, cyclooxygenase inhibition by indomethacin or meclofenamic acid (10 microM for each) significantly attenuated the rise in ANF associated with PAF administration (2.5 nmol). Prostaglandin F2 alpha (PGF) produced an immediate and dose-dependent increase in ANF secretion, which was significant at 0.01 mumol and reached 348 +/- 66% over baseline values after a 1-mumol injection. Prostaglandin E2 (PGE) generated a much smaller 98 +/- 25% increase after a 1-mumol administration. Furthermore, PGF but not PGE was released from isolated hearts immediately after PAF administration. PGF release reached a maximum of 0.06 nmol/min g Heart-1 1 min after PAF stimulation and had returned to undetectable baseline values by 6 min. Cyclooxygenase inhibition abolished the release of PGF after PAF, in addition to attenuating (by 60-70%) the increased secretion of ANF after PAF injection. These results demonstrate very clearly that PGF is the major mediator for PAF-stimulated ANF secretion. Such an interaction may provide an alternative mechanism to atrial distension for the secretion of ANF in pathologies such as myocardial infarction, where autacoids such as PAF and the PGs are released from damaged cardiac muscle and elevated plasma levels of ANF are observed. PMID- 8365357 TI - Growth hormone transgenes regulate the expression of sex-specific isoforms of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase in mouse liver and gonads. AB - The sexually dimorphic pattern of GH secretion regulates the expression of several steroidogenic enzymes in rat liver, including a male-specific 3 beta hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta HSD). Recently, we identified male-specific isoforms of immunoreactive 3 beta HSD in mouse liver [42 kilodaltons (kDa)] and gonads (47 kDa). To test whether GH can regulate the expression of these murine 3 beta HSDs, endogenous forms of 3 beta HSD were studied in transgenic mice expressing heterologous GH transgene products. Mice from five transgenic lines were used; two expressed GH transgenes encoding the phosphoenolpyruvate carboxykinase (PEPCK) promoter fused to either the human (h) GH (somatogenic and lactogenic) or bovine (b) GH (somatogenic) structural genes, and three expressed GH transgenes encoding the mouse metallothionein-1 (MT1) promoter fused to the hGH, hGH variant (hGHv), or bGH structural genes. Control mice were normal nontransgenic littermates. Expression of a male-specific (42 kDa) isoform of hepatic 3 beta HSD is dramatically suppressed in all transgenic mouse lines, as detected on Western immunoblots, without affecting a 47-kDa isoform expressed in livers of both male and female mice. This negative regulation was not observed in mouse kidney, which normally expresses two 3 beta HSD isoforms (in both sexes) with molecular masses similar to those in liver. Considering that PEPCK and MT1 promoters direct expression of GH fusion genes in both tissues, the inhibition of hepatic, but not renal, 3 beta HSD immunoreactivity suggests that GH affects sex-specific, rather than tissue specific, expression of 3 beta HSD. As in the liver, sex-specific expression of 3 beta HSD in the testis is also suppressed by heterologous GH, but with one notable difference. Only human-derived GH (MT1-hGH and MT1-hGHv) effectively inhibits expression of the 47-kDa sex-specific isoform of testicular 3 beta HSD, without affecting the 44-kDa isoform expressed in gonads of both male and female mice. These results suggest that the negative effects of heterologous GH on sex specific 3 beta HSDs may be mediated by PRL receptors in the testis and GH receptors in the liver. PEPCK-GH transgenes had little effect on testicular 3 beta HSD, possibly because this promoter (unlike MT1) is relatively inactive in this tissue. In the liver of male transgenics (PEPCK-hGH), loss of the sex specific (42-kDa) 3 beta HSD has little effect on the Km for dehydroepiandrosterone (DHEA; 11 microM) compared with that in normal controls (16 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8365358 TI - Glucocorticoid suppression of human placental fibronectin expression: implications in uterine-placental adherence. AB - Increased levels of glucocorticoids are associated with human parturition whether occurring before or at term. In the present study we examined the effects of glucocorticoids on placental fibronectin (FN) expression in cytotrophoblasts, isolated from human term placentas, to provide a potential mechanism through which glucocorticoids may influence uterine-placental adherence near parturition. Based on immunoassays, relative to controls, media levels of placental FNs bearing an oncofetal epitope (onfFN) were inhibited 65-80% by treatment with 10( 7) M dexamethasone (DEX) during experiments in which cumulative levels and daily release of onfFN were measured. DEX treatment increased human CG production by cytotrophoblasts approximately 3-fold without affecting the levels of total protein, suggesting that DEX treatment did not reduce placental function. DEX and cortisol inhibited onfFN expression with an EC50 of 2 and 16 nM, respectively. Other steroids were not effective in down-regulating onfFN expression, indicating that this was a glucocorticoid-specific response. In immunoprecipitation studies, treatment of cytotrophoblasts with 10(-7) M DEX for 3 days inhibited both release of labeled FN to the media and its incorporation into cell-associated material by approximately 80%. Results from Northern blotting indicated that DEX treatment suppressed levels of FN messenger RNA approximately 90% relative to controls. Levels of labeled laminin in media were inhibited approximately 80% by a 3-day treatment with 10(-7) M DEX, suggesting that glucocorticoids may coordinately suppress the synthesis of multiple extracellular matrix proteins in cytotrophoblasts. In our model, we propose that glucocorticoids may suppress placental extracellular matrix protein synthesis, which could lead to decreased uterine-placental adherence and be associated with parturition. PMID- 8365359 TI - Effects of sex and pregnancy hormones on growth hormone and prolactin receptor gene expression in insulin-producing cells. AB - During pregnancy, marked hyperplasia of the pancreatic islet cells has been observed. This effect may be mediated by the pregnancy-associated peptide hormones, placental lactogen, PRL, and GH, which were previously shown to be mitogenic to beta-cells in vitro. To study whether the responsiveness of islet cells to these hormones is regulated on the receptor level, GH and PRL receptor gene expression was studied in pancreata from male rats and virgin, pregnant, and lactating female rats and in cultured islets and insulinoma cells (RIN-5AH) in response to various hormones. The mRNA levels were quantitated by ribonuclease protection assay, using probes specific for mRNA encoding, extracellular and intracellular domains of the GH receptor, and short and long forms of the PRL receptor, respectively. Specific transcripts for the GH receptor were present in pancreas, islets, and RIN-5AH cells. Furthermore, as previously observed in RIN 5AH cells, a predominant expression of the long form of PRL receptor vs. the short form was also found in pancreas and islet cells. Male and nonpregnant female pancreas did not differ significantly in their levels of GH and PRL receptor mRNAs. On day 14 of pregnancy, increases in both GH and PRL receptor mRNA levels were observed (1.7- and 2.4-fold, respectively), and a further increase occurred in late pregnancy (day 19), when GH and PRL receptor mRNA levels were 2.7- and 3.9-fold higher than those in the nonpregnant state. mRNA levels returned toward the basal level during lactation. In the cultured islets, PRL receptor mRNA levels were markedly increased by GH and PRL (3.5- and 6.5 fold, respectively) after exposure for 24 h, whereas estradiol and testosterone had modest stimulating effects (1.8- and 1.5-fold increases, respectively). Dexamethasone induced a 2.5-fold increase in GH receptor mRNA levels, and a weak stimulatory effect was also observed for progesterone. In RIN-5AH cells, the effect of dexamethasone on GH receptor mRNA was detectable after 2 h and maximal after 16 h. In contrast, the effects of GH and PRL on PRL receptor mRNA required 24-48 h of exposure. The effective doses were within the physiological ranges. In conclusion, these results show a differential hormonal regulation of GH and PRL receptor gene expression in the pancreatic islets, which may play a role in the adaptive beta-cell growth during pregnancy. PMID- 8365360 TI - Differential expression of A- and B-subtypes of cholecystokinin/gastrin receptors in the developing calf pancreas. AB - Cholecystokinin (CCK)/gastrin receptors were characterized in calf pancreatic plasma membranes from newborns, 28- and 119-day-old milk-fed preruminants, and 119-day-old weaned ruminants. Scatchard analysis of [125I]Bolton-Hunter reagent [Thr28,Nle31]CCK-(25-33) binding indicated two classes of binding sites: high affinity sites exhibited significant higher affinity and binding capacity (P < 0.05) in 119-day-old ruminants than in 119-day-old preruminants (Kd = 0.13 +/- 0.02 vs. 0.35 +/- 0.08 nM; binding capacity (Bmax) = 53 +/- 12 vs. 18 +/- 5 fmol/mg protein). Pharmacological analysis using selective agonists and antagonists indicated the expression of the CCK-A receptor at birth, whereas the CCK-B receptor predominated at postnatal stages. At all stages, the binding was inhibited by guanosine 5'-[gamma-thio]triphosphate. Binding site identification by photoaffinity labeling showed that at birth, the labeling occurred mainly on a 78- to 96-kilodalton (kDa) component. In milk-fed animals, aged 28 and 119 days, two membrane-binding components were labeled at 78-96 and 43-52 kDa. In 119-day old ruminants, labeling occurred mainly on a 40- to 47-kDa protein. Deglycosylation by endo-beta-N-acetylglucosaminidase-F of the 40- to 47- and 43- to 52-kDa components resulted in the formation of a 37-kDa membrane protein. Consequently, this study demonstrated 1) the differential expression of CCK-A and -B receptors in developing calf pancreas, 2) the predominance of CCK-B receptors in normal pancreas, and 3) the maturation of CCK-B receptors during the weaning period, which includes the glycosylation level. These results suggest that CCK may play a predominant role during the early postnatal development, while gastrin and CCK-B receptors can function progressively to regulate proliferation and exocrine secretion in the calf pancreas, especially from the weaning period. PMID- 8365361 TI - Gene expression and serum thyroxine-binding globulin are regulated by adrenal status and corticosterone in the rat. AB - Supraphysiological doses of glucocorticoids reduce serum T4-binding globulin (TBG) concentrations when administered to human subjects. Studies were performed in rats to determine if glucocorticoid administration alters serum TBG in another species, if circulating concentrations of glucocorticoids tonically affect serum TBG concentrations, and if changes in TBG production are likely to be a cause of the glucocorticoid-induced changes in serum TBG concentrations that are observed in humans. The serum TBG-binding capacity was 14.9 +/- 2.3 nmol/liter in adrenalectomized male rats compared to 6.6 +/- 1.0 nmol/liter in intact male rats and 4.8 +/- 0.9 nmol/liter in adrenalectomized male rats that received corticosterone in a dose equal to or less than the replacement dose, as assessed by thymus weight (P < 0.01 for serum TBG in adrenalectomized vs. intact or adrenalectomized corticosterone-treated groups). Hepatic TBG mRNA content, as assessed by polymerase chain reaction amplification and expressed as a ratio of beta-actin mRNA content, was 0.10 +/- 0.03 density units in intact male rats, 0.59 +/- 0.17 density units in adrenalectomized male rats, and 0.05 +/- 0.02 density units in adrenalectomized corticosterone-treated male rats (P < 0.03 for adrenalectomized vs. intact or adrenalectomized corticosterone-treated rats). Adrenalectomy increased the serum TBG-binding capacity in female rats (intact female rats, 13.9 +/- 1.0 nmol/liter; adrenalectomized female rats, 39.0 +/- 6.4 nmol/liter; P < 0.01). These studies indicate that serum TBG is tonically down regulated by adrenal glucocorticoids, because corticosterone decreases the TBG production rate, probably at the level of transcription. This effect is similar to that described for corticosterone-binding globulin, but differs from that for many proteins of the serine protease inhibitor family that are related to TBG. PMID- 8365362 TI - Stimulation of prolactin secretion in the pig: central effects of relaxin and the antiprogesterone RU 486. AB - Our previous study has shown that oral administration of a potent progesterone antagonist, RU 486, caused a marked elevation of plasma concentrations of both PRL and progesterone in hysterectomized pigs bearing aging corpora lutea. Hysterectomized pigs (hysterectomy performed on day 8; estrus = day 0) were subjected to cranial surgery for chronic placement of a head-mounted stereotaxic apparatus for intracerebroventricular (icv) administration of relaxin (300 U once daily on days 111 and 113; n = 6) and RU 486 (4 mg once daily on days 111, 113, and 115; n = 5) to test whether relaxin and RU 486 exert their actions within the central nervous system and/or pituitary gland to affect PRL and GH secretion. Control pigs (n = 3) received icv injection of vehicle. Intensive blood sampling revealed that icv injection of relaxin on day 111 markedly increased the plasma PRL concentration from 8 to 38 ng/ml within 10 min (P < 0.01). An identical icv injection of relaxin on day 113 caused only a modest increase in PRL, but the overall mean concentration of PRL after relaxin treatment was greater than that before treatment (14 vs. 8 ng/ml; P < 0.05). Intracerebroventricular injection of RU 486 on day 111 greatly elevated plasma PRL. The increase in PRL lasted more than 2 h, with several peak increases of 18-29 ng/ml (P < 0.01). The PRL response to subsequent icv infusion of RU 486 on days 113 and 115 was blunted, but the overall mean concentration of PRL (14 ng/ml) after icv injection of RU 486 remained greater (P < 0.01) than that before treatment (9 ng/ml). In contrast, PRL concentrations in the control group remained unchanged after injection. Plasma concentrations of GH, relaxin, and progesterone were significantly altered in neither hormone- nor vehicle-treated groups during this brief period of sequential blood sampling. This study provides strong evidence that relaxin has a central role in modulating PRL secretion in the pig. In addition, the antagonistic effects on progesterone receptor by RU 486 in the central nervous system and/or pituitary gland caused an abrupt increase in PRL secretion in these hysterectomized gilts. PMID- 8365363 TI - Angiotensin-II induces changes in the cytosolic sodium concentration in bovine adrenal glomerulosa cells: involvement in the activation of aldosterone biosynthesis. AB - The homeostasis of cytosolic free calcium ([Ca2+]i) and intracellular free sodium ([Na+]i) are linked in many cell types. We, therefore, studied the effect on [Na+]i of two physiological stimulators of aldosterone synthesis that trigger the calcium messenger system, angiotensin-II (Ang II) and potassium ion (K+), in cultured bovine adrenal glomerulosa cells, using the intracellular fluorescent probe for sodium, sodium benzofuran isophthalate. Ang II induced a concentration dependent and sustained increase in [Na+]i, from a resting value of 9.2 +/- 3.5 to a maximum of 48.5 +/- 5.5 mM (n = 14). This [Na+]i response was mediated by receptors of the AT1 subtype, because it was abolished by losartan (DuP 753). K+ (15 mM) induced a weaker [Na+]i response, from 5.9 +/- 2.6 to 16.8 +/- 2.5 mM (n = 9). In freshly prepared cells, basal [Na+]i was significantly higher (23.9 +/- 1.8 mM; n = 14; P < 0.01) than in cultured cells. Atrial natriuretic peptide, which is known to affect sodium transport in various cell types, did not alter the [Na+]i response elicited by Ang II. Ethylisopropylamiloride, an inhibitor of Na+/H+ exchange, and dichlorobenzamyl, an inhibitor of Na+/Ca2+ exchange, both inhibited in a concentration-dependent manner the Ang II- and K(+)-induced aldosterone response. Isoosmotic replacement of extracellular Na+ markedly reduced basal aldosterone synthesis. Under these conditions, the concentration response curve for Ang II-induced aldosterone synthesis was shifted to the right, and its maximum was strikingly diminished. These results show that Ang II and, to a lesser extent, K+ induce significant changes in [Na+]i in bovine glomerulosa cells. These [Na+]i changes probably occur through the Na+/H+ and Na+/Ca2+ exchangers and are likely to play a role in activation of the steroidogenic cascade. PMID- 8365364 TI - Location of a glucose-dependent response region in the rat S14 promoter. AB - The rat S14 gene provides an excellent model to examine the DNA sequences associated with carbohydrate regulation of hepatic gene transcription. We constructed internal deletions within 5 kilobases of the 5'-up-stream region and ligated these to a luciferase reporter gene. The constructs were transfected into primary hepatocytes and pancreatic HIT cells. In hepatocytes, an increase in the medium glucose concentration led to a parallel increase in endogenous mRNA S14 content and transfected luciferase reporter activity driven by 5 kilobases of the S14 promoter. Internal deletions of several sequences from -2706 to -285 each led to a decrease in glucose-stimulated activity, suggesting that multiple elements are necessary for the transcriptional response to glucose. Deletion from -1583 to -1069 nearly abolished the glucose effect in both cell types and delineated the carbohydrate response element (CHORE). The CHORE deletion was specific for glucose, because it did not alter the response to thyroid hormone, another known regulator of this gene. Although the CHORE sequence did not confer glucose activation to either a heterologous promoter or the basal S14 promoter (bases 285 to +19), a 5-fold enhanced response was observed when two copies of the CHORE were ligated to the first 2110 basepairs of the S14 promoter. The results suggest that the CHORE contains a carbohydrate regulatory element and operates as an enhancer in concert with other sequences within the S14 gene. PMID- 8365365 TI - Differential regulation of human progesterone receptor A and B form-mediated trans-activation by phosphorylation. AB - Hormone-dependent phosphorylation of progesterone receptors (PRs) plays a functional role in their transcriptional activity. However, hormone-independent phosphorylation has also been shown to modulate the chicken PR-mediated trans activation in the presence of phosphorylating agents. The present study was designed to investigate the effects of protein kinase A- and protein kinase C mediated signal transduction pathways on the regulation of the activity of the two forms of human PR (hPRA and hPRB). Similar to chicken PR, hPR was activated by 8-bromo-cAMP (8-Br-cAMP) in the absence of ligand, whereas 8-Br-cAMP synergized with the progestin agonist R5020 to amplify hPRA- and hPRB-mediated reporter activity. Interestingly, the effect of 8-Br-cAMP was much more pronounced on hPRA-induced trans-activation than on hPRB. This differential regulation by 8-Br-cAMP could also be mimicked by okadaic acid. Both mouse mammary tumor virus-thymidine kinase-chloramphenicol acetyl transferase and progesterone response element-thymidine kinase-chloramphenicol acetyl transferase showed a similar response to 8-Br-cAMP in the presence of R5020. Protein kinase C, on the other hand, did not discriminate between hPRA- and hPRB-mediated trans activation. Unlike 8-Br-cAMP, phorbol 12-myristate 13-acetate did not cause marked ligand-independent trans-activation through either of the two receptor forms. RU486, an antagonist of progestin, preferentially blocked R5020-induced trans-activation compared to R5020 + 8-Br-cAMP synergism. As expected, H-89, a specific inhibitor of protein kinase A was more effective in inhibiting ligand independent activity. Western analysis of transfected receptors suggested that 8 Br-cAMP and 8-Br-cAMP + R5020 but not R5020 alone down-regulated the level of hPRB in COS-1 cells. Only marginal modulation of hPRA levels was observed with R5020 treatment in the presence and absence of 8-Br-cAMP. These data suggest that R5020 and 8-Br-cAMP mediate PR-dependent transactivation through distinct pathways, and that phosphorylation can differentially regulate the activity of hPRA and hPRB forms, an observation which may be important for selective target gene activation in vivo by progestins. PMID- 8365366 TI - Effect of a major histocompatibility complex class I peptide on insulin-like growth factor-I receptor internalization and biological signaling. AB - Previous studies have shown that a peptide derived from the murine major histocompatibility complex class 1 (MHC-1) antigen inhibits insulin receptor internalization and enhances insulin action. Consequently, we have studied the effect of this peptide [Dk-(62-85)] derived from the MHC-1 antigen on insulin like growth factor-I (IGF-I) internalization and action. When Chinese hamster ovary cells that overexpress human IGF-I receptors were incubated in the presence or absence of 30 microM Dk-(62-85), IGF-I internalization was inhibited by 43.9 +/- 1.7% (P < 0.005). This inhibitory effect was dose responsive, with a half maximal effect at 8 microM and a maximal effect at 30 microM. The peptide did not affect IGF-I receptor autophosphorylation or ligand-induced phosphorylation of an endogenous substrate, pp185, in vivo. When added alone, the peptide increased glucose transport into Chinese hamster ovary cells by 66.3 +/- 16.0%, whereas when the peptide was added together with IGF-I, ligand-stimulated glucose transport was inhibited. In conclusion, 1) the MHC-1-derived peptide Dk-(62-85) inhibits IGF-I internalization in a dose-responsive fashion; 2) Dk-(62-85) does not affect receptor kinase activity, as IGF-I receptor autophosphorylation and endogenous substrate phosphorylation are unaltered; and 3) Dk-(62-85) stimulates glucose transport by itself, but inhibits IGF-I stimulated transport. PMID- 8365367 TI - Luteinizing hormone-releasing hormone (LHRH) in rat prostate: characterization of LHRH peptide, messenger ribonucleic acid expression, and molecular processing of LHRH in intact and castrated male rats. AB - Continuous administration of LHRH agonist suppresses the pituitary-gonadal axis, achieving chemical castration. Thus, LHRH agonist has been used as an alternative (to surgical castration) for the treatment of steroid-dependent prostate cancer. However, recent reports have demonstrated that LHRH agonist had a direct inhibiting effect on prostate cancer cell proliferation and that cancerous prostate tissue contained a LHRH-like peptide. In this paper we are reporting for the first time that the normal rat ventral prostate contained immunoactive and bioactive LHRH as well as its precursor molecule, pro-LHRH. Our investigation showed that the LHRH concentration in prostate increased 2 weeks after castration from 1.68 +/- 0.09 to 3 +/- 0.2 pg/mg tissue (P < 0.001). At the same time, the concentration of pro-LHRH decreased from 149 +/- 6.5 to 68 +/- 6.8 pg/mg tissue (P < 0.001). Furthermore, intact rat prostate expressed LHRH mRNA, which increased 13-fold 2 weeks after castration. In summary, the prostate of intact Sprague-Dawley rats has the capacity to produce the LHRH precursor and process it to the mature decapeptide, and this production/processing increases significantly after castration. PMID- 8365368 TI - Lactation alters neuropeptide-Y and proopiomelanocortin gene expression in the arcuate nucleus of the rat. AB - To identify possible factors associated with lactation that may be involved in the suppression of GnRH neuronal function, we have examined whether lactation induces changes in arcuate nucleus neuronal function, focusing on changes in neuropeptide-Y (NPY) and POMC neuronal activity. Animals were studied during diestrous day 1 of the estrous cycle or during day 10 postpartum. Lactating animals had their litters adjusted to eight pups on day 2 postpartum. Brain tissue was removed to measure NPY peptide content in the median eminence (ME) or the ME-arcuate nucleus (ME-ARC) and to quantify NPY or POMC mRNA by in situ hybridization, using 35S-labeled antisense riboprobes. The NPY peptide content was significantly increased in the ME (1.8-fold) and ME-ARC (1.5-fold) during lactation compared to those on diestrus. The NPY mRNA content throughout the ARC did not differ between diestrous and lactating animals. However, if specific subdivisions of the ARC were examined, a significant increase (1.8-fold) in NPY mRNA in the ARC-C region of the ARC (at the plane of the dorsal medial hypothalamic nucleus) was observed during lactation. Dorsal to the ARC in this same plane, there was also an induction of NPY expression in cells lateral to the dorsal medial hypothalamic nucleus. The increases in NPY mRNA in the ARC-C region of the arcuate nucleus persisted for at least 24 h after removal of the suckling stimulus. The other subdivisions of the ARC did not show any differences in NPY mRNA between diestrus and lactation. The POMC mRNA content was decreased by 20 30% during lactation compared with that on diestrus. The effects of lactation to decrease POMC mRNA content were not specific to any subdivision of the ARC, but were observed throughout the entire ARC. Given that lactation is an estrogen deficient state, the increase in NPY neuronal activity, as indicated by increased gene expression in the caudal portion of the ARC and increased content in the ME, could play an inhibitory role in the regulation of GnRH secretion. However, the decrease in POMC neuronal activity, as suggested by the decrease in gene expression throughout the ARC, would not appear to be involved in the suppression of GnRH neuronal activity. These changes in ARC neuronal function could be related to hormonal changes or metabolic signals regulating food intake during lactation. PMID- 8365369 TI - Lactotrope differentiation in rats is modulated by a milk-borne signal transferred to the neonatal circulation. AB - We have previously reported that normal differentiation of PRL-secreting cells in neonatal rats requires a maternal signal specific to the first few days of lactation. Subsequently, we found that milk proteins from this period had a greater capacity than those from later in lactation to stimulate lactotrope differentiation in vitro, suggesting that the maternal signal was a milk-borne peptide. We reasoned in the present study that if this were the case, the signal should be present in the serum of suckling pups, and its level should reflect that in mothers' milk. To test this hypothesis, we first compared serum from 3 day-old pups with that from newborn pups that had not yet suckled. Anterior pituitary cells from 1-day-old pups were cultured for 6 days in the presence of various serum samples (0.01-1.0% by volume). Lactotrope differentiation was assessed using a reverse hemolytic plaque assay for PRL. Serum from 3-day-old pups was more effective (P < 0.01; n = 4) than that from unsuckled newborns at stimulating lactotrope differentiation in vitro (to 3.5 +/- 0.5% and 1.5 +/- 0.5% of all anterior pituitary cells, respectively). Next, we tested whether this increase in serum bioactivity in 3-day-old pups required maternal influences restricted to the first few days of lactation. Newborn pups were placed with foster mothers that had been lactating for 0 or 7 days. When the pups were 3 days old, their serum was tested for lactotrope-differentiating activity. Serum from pups placed with day 0 foster mothers (control) increased the abundance of PRL cells to 2.4 +/- 0.3% of all cells (P < 0.01; n = 3), whereas serum from pups placed with day 7 foster mothers failed to stimulate lactotrope differentiation. In similar experiments, litters placed the day after birth with day 7 foster mothers were separated on day 3 postpartum for 3 h, after which littermates were allowed to suckle for 90 min on different foster mothers on day 3 or 9 of lactation. This brief suckling bout increased (P < 0.01; n = 3) the capacity of serum from pups on day 3 mothers to stimulate PRL cell differentiation (to 3.9 +/ 0.4%) above that of serum from littermates placed with day 9 foster mothers (to 1.8 +/- 0.2%). Finally, the differentiating activities in pup serum and mothers' milk eluted from gel filtration chromatography in identical fractions (4-8 kilodaltons).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8365370 TI - Characterization of thyroid hormone binding to apolipoprotein-E: localization of the binding site in the exon 3-coded domain. AB - Apolipoprotein-E (apoE) has been shown by noncovalent binding and photoaffinity labeling with [125I]T4 to possess a single L-T4 binding site with a K5 of about 3 x 10(7) M-1 and a relative affinity for analogs of L-T4 = D-T4 = rT3 = triiodothyroacetic acid > L-T3. T4 binding was not affected by the flavonoid EMD 21388 or heparin, but was inhibited by diclofenac = mefenamic acid > furosemide. Localization of the T4 site to the N-terminal 62-amino acid region of the mature peptide coded by exon 3 was deduced from the following evidence. 1) The N terminal 15- to 26-kilodalton (kDa) fragments (within residues 1-160 to 210), but not the approximately 10- to 11-kDa fragments (within residues approximately 220 299), were labeled by [125I]T4. 2) Variants apoE2 and apoE4, with nonconservative mutations at positions 112 and 158 (the latter unable to interact with the apoB/E receptor), maintained the ability to bind T4. 3) Monoclonal antibodies MAb 1D7 and 3H1 (epitopes at positions 139-169 and 243-272, respectively) failed to inhibit T4 binding, but MAb 6H7 (epitope at 1-125) decreased labeling by about 24%. 4) Polymers of apoE were specifically labeled despite the interaction between amphipathic alpha-helices of the exon 4-encoded region (63-299). We conclude that apoE, as previously observed with apoA-I and apoB, possesses a T4 binding domain separate from the lipid-binding domain and distinct from both the heparin- and the cell receptor-binding sites. Thyroid hormone binding by apoE may facilitate uptake of the hormone by cells through apoB/E receptors, which are widely distributed in tissues. PMID- 8365371 TI - Immunological identification of the protein-producing masculine differentiation of the Wolffian duct in the fetal mouse: western blot analysis and determination of the biological activity. AB - Recently, we identified a protein in the developing male reproductive tract of the fetal mouse which induced Wolffian duct differentiation in vitro in the absence of testis or testosterone. In this paper, we further evaluated the masculinizing role of this protein using an immunological approach. Thus, we purified a 72K protein from the 18-day-old male fetal reproductive tracts, prepared an antibody against the protein, and determined the role of this protein in producing masculine differentiation of the Wolffian duct using the polyclonal antibody against the protein. We demonstrate that the antibody reacted with the purified 72K protein, producing only one immunoreactive band around the 72K region in Western blot analysis. However, it reacted with 72K and 63K proteins present in the 18-day-old male reproductive tract. Both of these immunoreactive bands disappeared when the antibody was pretreated with the purified antigen. Nonimmune immunoglobulin G (IgG) produced no reactive bands with the extract of the male reproductive tracts. The IgG preparation of the immune serum specifically prevented Wolffian duct differentiation when tested in organ culture containing 13-day-old fetal male or female reproductive tracts in the presence of testis or testosterone (1 micrograms/ml) in a dose-dependent manner. No effect was found on the development of other organs, namely testis, Mullerian duct, and urogenital sinus, that were included in the organ culture. Nonimmune IgG, as expected, produced no effect on Wolffian duct differentiation. Western blot analysis of male and female reproductive tracts indicated a difference in their reactivities with this antibody. In females, the reactivity to the proteins around the 72K and 63K regions was very weak compared to that found with male proteins in those regions. Both of the above bands of the female reproductive tract disappeared when the antibody was pretreated with an excess of female reproductive tract extract, but in males, only the 63K band disappeared, whereas its 72K band remained. In conclusion, it appears that a 72K protein of the male reproductive tract plays a role in the Wolffian duct differentiation of the fetal mouse. PMID- 8365372 TI - Brain corticotropin-releasing hormone- and interleukin-1 beta-induced suppression of specific antibody production. AB - CRH serves as a central nervous system mediator of autonomic and visceral responses to stress. In addition, central infusion of CRH has a role in the modulation of in vitro correlates of cell-mediated immune function, such as natural killer cell activity and T-lymphocyte proliferation. The present study examined the effects of central CRH on an integrated in vivo immune response, specific antibody production to a novel antigen. Synthetic rat CRH (1.0 micrograms) microinjected into the lateral ventricle significantly (P < 0.001) slowed the induction of a specific immunoglobulin G (IgG) antibody response to the T-cell-dependent antigen keyhole limpet hemocyanin (KLH) after either primary or secondary immunization. CRH-induced suppression of the IgG response in vivo was found after immunization with a low threshold dose of KLH, but not when a 100 fold increased dose of antigen was given. Administration of CRH 20 min before immunization reduced the antibody response, whereas CRH infusion 24 h after KLH exposure failed to alter antibody levels, suggesting that CRH alters initial antigen processing. These effects of CRH on an in vivo antibody response were due to the infusion of CRH into the brain, as a 1.0-micrograms dose of CRH injected either ip or sc had no effect. In addition, central coadministration of the CRH antagonist alpha-helical CRH-(9-41) significantly blocked the immunosuppressive action of CRH. Finally, as central interleukin-1 beta has been reported to modulate cellular immunity, we examined the effect of central infusion of interleukin-1 beta on the KLH antibody response and found that intracerebroventricular interleukin-1 beta (50 ng) produced a significant (P < 0.001) suppression of the IgG response to KLH. These findings extend previous data on central CRH-induced suppression of in vitro measures of cellular immunity and demonstrate that CRH acts in the brain to reduce an in vivo antibody response. PMID- 8365373 TI - The effect of insulin and insulin-like growth factor-I on glucose transport in normal and small for gestational age fetal rats. AB - In a model of asymmetric small for gestational age (SGA) fetal growth retardation, we have previously found that glucose transport is decreased in lung (an organ whose growth is restricted) and unaffected in brain (growth is normal). The SGA model alters a number of physiological and metabolic factors that may decrease glucose transport, thereby causing growth retardation. Specifically, insulin and insulin-like growth factor-I (IGF-I) concentrations are diminished in SGA fetuses. We hypothesized that the specific modulation by these factors of gene expression of a glucose transporter, Glut-1, is impaired. We performed bilateral uterine arterial ligation in pregnant rats on day 19 of gestation (term = 21.5 days) and obtained fetal brain, lung, and skeletal muscle on day 20. Lung and muscle explants and monolayers of glial cells and type II pneumocytes were cultured in the presence or absence of insulin or IGF-I for 24 h. Glucose uptake and levels of Glut-1 protein and mRNA were similar in brains of SGA and control fetuses and were not affected by treatment with insulin or IGF-I. Treatment with insulin or IGF-I increased glucose uptake and levels of Glut-1 protein and mRNA in a dose-dependent manner in lung and muscle from control fetuses. However, the response in SGA lung was not as great as that in controls. SGA muscle demonstrated no significant response to either hormone. These findings suggest that changes in glucose transport modulation might contribute to the development of asymmetric growth retardation, and that maintenance of normal transporter function and expression in brain may play a role in sparing its growth. PMID- 8365374 TI - Stretch-induced atrial natriuretic factor release utilizes a rapidly depleting pool of newly synthesized hormone. AB - Atrial muscle stretch is widely believed to be the main stimulus for atrial natriuretic factor (ANF) release. However, a few reports have shown that although stretch induces an immediate increase in ANF output, this release rapidly decays even though hormone stores are not significantly depleted. In the present work, this phenomenon was studied in an isolated rat atria preparation using double isotope labeling. The tissue was labeled with [14C]leucine for 3 h followed by a 1-h chase, and then with [3H]leucine for 1 h. A final 1-h chase period was conducted with the tissue under basal (0.2-g load) or stretched (5-g load) conditions. During this final chase period, the [14C]ANF represented older, stored ANF and the [3H]ANF represented the newly synthesized peptide. After both the [14C]- and [3H]leucine pulses, immunoprecipitable isotope incorporated into ANF appeared in the chase medium within the first 10 min and stabilized to lower levels after 20 min of chase. Stretch resulted in an immediate significant increase in immunoreactive ANF release and a decrease in the medium [14C]ANF specific activity (SA). However, no change was observed in the medium [3H]ANF SA but the tissue SA tended to decrease. It is concluded that a portion of ANF is immediately and preferentially released upon synthesis, while the remainder is taken up into tissue stores and released from them at a lower rate. The secretory response to stretch was demonstrated to consist of a rapid, short-lived burst of newly synthesized ANF, suggesting an increased translocation of newly synthesized hormone into a stretch-sensitive, rapidly depletable pool. Given the nature of this pool, additional factors yet to be characterized likely come into play to maintain chronically elevated circulating levels of ANF. PMID- 8365375 TI - Transforming growth factor beta 1-like immunoreactivity in the pituitary gland of the rat: effect of estrogen. AB - We have recently shown that transforming growth factor-beta 1 (TGF beta 1) is produced in the rat pituitary gland and inhibits the secretion of PRL and the estrogen-induced growth of lactotropes. In this study, we sought to ascertain whether TGF beta 1 inhibits lactotropic functions by an autocrine or paracrine mechanism. Our techniques consisted of localizing the pituitary distribution of the growth factor immunoreactivity and measuring changes in pituitary TGF beta 1 and PRL levels in the presence and absence of estrogen in ovariectomized animals. With the use of standard immunohistochemical techniques, we observed that in cyclic females and ovariectomized rats, 60 +/- 7% of the cells exhibiting TGF beta 1-like immunoreactivity in the anterior pituitary were lactotropes. In addition, the melanotropes in the intermediate lobe appeared to be TGF beta 1 immunopositive. Treatment with estrogen for 7 days reduced the number of TGF beta 1-immunoreactive lactotropes. Immunoreactive TGF beta 1 was also detectable in anterior pituitary extracts using a specific RIA. Estrogen treatment decreased the level of TGF beta 1 in the anterior pituitary extracts from ovariectomized rats. TGF beta 1 immunoreactivity was inversely proportional to the overall size of the anterior pituitary and the concentrations of PRL, as measured in both the anterior lobe extracts and plasma. These results suggest that lactotropes may serve as a site of TGF beta 1 synthesis and that the production of TGF beta 1 in these cells can be negatively influenced by PRL stimulation through the action of the lactotrope-proliferating hormone, estrogen. Furthermore, these data support the notion that TGF beta 1 controls lactotropic function by an autocrine mechanism. PMID- 8365376 TI - Atrial stretch induces rapid increase in brain natriuretic peptide but not in atrial natriuretic peptide gene expression in vitro. AB - Pressure and volume overload in vivo is characterized by induction of the expression of two cardiac hormones, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), but whether stretch directly or other pathophysiological factors associated with cardiac overload cause the activation of these genes is not known. In the present study we examined the effect of short term (from 30 min to 2 h) direct myocardial stretch on atrial ANP and BNP synthesis and release in modified perfused rat heart preparation that enabled the stepwise distension of the right atrium by pressures approximating those found in vivo. The increase in right atrial pressure by 3.6 mm Hg for 2 h resulted in a 3.3- (p < 0.001) and 1.7-fold (p < 0.02) increase in the rate of IR-ANP and IR BNP release, respectively, into the perfusate. The maximal increase in both ANP and BNP release was seen after 20 min distension. Thereafter the perfusate IR-ANP and IR-BNP concentration gradually decreased, reaching control values within 2 hours. Chromatographic analysis showed that the hearts primarily release the active, processed 28- and 45-amino acid ANP- and BNP-like peptides, respectively, both before and during atrial stretch. Atrial stretch induced rapid stimulation of BNP gene expression: 1.9- (p < 0.001) and 4.5-fold (p < 0.001) increase in right auricular BNP mRNA levels after 1.0 and 2.0 hours' stretching, respectively, was found on Northern blot analysis, while no change was seen after 30 min distension. In contrast, stretching for up to 2 h did not change auricular ANP mRNA, IR-ANP or IR-BNP levels. Our results show for the first time that atrial stretch induces rapid stimulation of both synthesis and secretion of BNP. The induction of BNP gene expression in the very early stages of cardiac overload mimics the induction of protooncogenes and occurred without involvement of humoral or neural factors. The lack of response of atrial ANP mRNA levels demonstrates that the regulation of BNP gene expression differs from that of ANP. PMID- 8365377 TI - Growth hormone receptor and growth hormone-binding protein messages in mouse placenta contain the exon analogous to human exon 3. AB - Growth hormone receptor (GHR)-encoding messages from the human placenta and other tissues have been recently characterized by several investigators. Of particular interest is the finding that exon 3 is deleted from the mRNA encoding GHR in human placenta, but not in maternal tissues. We have used a reverse transcriptase polymerase chain reaction (RT-PCR) technique to amplify the distinct mRNAs encoding GHR and GH-binding protein (GHBP) in the mouse placenta and liver, followed by restriction analysis, to determine whether an analogous deletion exists in these mRNAs. The restriction analysis and sequencing of the PCR products shows that the mRNAs encoding GHBP and GHR in the mouse placenta do not have a deletion analogous to that found in human placental GHR mRNA. PMID- 8365378 TI - alpha 1-Antitrypsin- and anchorage-independent growth of MCF-7 breast cancer cells. AB - alpha 1-Antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACHY) are closely related protease inhibitors, synthesized primarily by the liver, which play major roles in modulation of the inflammatory response. Previously, we had shown that MCF-7 human breast cancer cells were able to synthesize active alpha 1 AT and alpha 1-ACHY and that the synthesis of both inhibitors varied among different MCF-7 sublines. We now show that when MCF-7(ML) cells (a subline synthesizing low levels of alpha 1-AT) are grown in soft agar in medium depleted of its trypsin inhibitory capacity (i.e. alpha 1-AT-free), addition of alpha 1-AT (50 micrograms/ml) significantly reduces colony formation in both the presence and absence of estradiol (34% and 44%, respectively). Under these conditions, incubation with 10(-7) M estradiol alone increased colony formation 2- to 3-fold. Colony formation was also significantly reduced by serum leukocyte protease inhibitor, which, like alpha 1-AT, is a potent inhibitor of elastase-like enzymes. We also found that a variety of inflammatory mediators, cytokines, and steroid hormones are able to stimulate synthesis of alpha 1-AT and alpha 1-ACHY by MCF-7 cells. Stimulation by interleukin-6 (IL-6; 200 U/ml), epidermal growth factor (4 nM), and estradiol (10(-7) M) was 2- to 3-fold, whereas stimulations by tetradecanoylphorbol-13-acetate (TPA; 80 nM) and IL-1 (10 U/ml) were 2- to 5-fold and 5- to 10-fold, respectively. In each instance, protein synthesis, monitored by immunoprecipitation of 35S-labeled proteins followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and steady state mRNA levels, monitored by Northern blot analysis with specific cDNA probes, increased to the same extent. Consistent with their ability to stimulate alpha 1-AT synthesis, TPA and IL-1 reduced colony formation in the absence of estradiol by 65% and 63%, respectively. In addition, the effects of both TPA and IL-1 could be reversed by antibody to alpha 1-AT. These results suggest that local synthesis of alpha 1-AT and possibly other protease inhibitors may be important in regulating the tumorigenic potential of MCF-7 breast cancer cells. PMID- 8365379 TI - The effect of very long-chain n-3 fatty acids on immune-related skin diseases. PMID- 8365380 TI - Predictive equations for basal metabolic rates of Indian males. AB - The article deals with the generation of a prediction equation for basal metabolic rate (BMR) of well-nourished Indian males, from prospective measurements on 121 males, using a single validated technique. The equation related BMR to simple measures such as weight (WT) and age, and was given by: BMR (kJ/d) = 48.7 * WT-14.1 * AGE + 3599. The equation was internally as well as externally validated against other Indian databases and the net differences of < 2% (100 kJ/d), were non-significant. Interestingly, American BMRs were predicted to within 0.5% (28 kJ/d) by this equation, while European BMRs were significantly higher than predicted by 6.3% (433 kJ/d). Similar results were obtained on validating the American and European data against the equations of C. K. J. Henry & D. G. Rees (1991) Eur J. Clin. Nutr. 45, 177-185. Such results suggest that there are no differences in the BMR of age- and weight-matched Asian Indian males, other tropical populations and Americans. This has implications in the estimation of energy expenditure and hence energy requirements for these populations. PMID- 8365381 TI - Role of zinc supplementation in the rehabilitation of severely malnourished children. AB - A double-blind study was conducted to assess the role of zinc supplementation in the rehabilitation of severely malnourished children. Thirty-three children with severe protein-energy malnutrition received either 40 mg of zinc as zinc sulphate or a placebo during their rehabilitation in addition to the diet containing about 700 kJ and 3-4 g protein per kg body weight/day. Their clinical and biochemical responses were examined. Clinical response and serum albumin synthesis were found to be similar in both the groups. The leukocyte (micrograms/10(10) cells) and plasma zinc levels (micrograms/dl) showed a significant (P < 0.001 and P < 0.01) increase from 46.9 +/- 5.490 to 107.2 +/- 13.224 and 80.4 +/- 9.972 to 107.5 +/- 11.822, respectively, after zinc supplementation. The placebo group also showed a significant (P < 0.025) increase in leukocyte zinc from 45.7 +/- 4.409 to 70.9 +/ 8.414. However, the plasma zinc in the placebo group fell from 83.6 +/- 10.363 to 68.2 +/- 7.031. Plasma copper showed a significant improvement in both zinc supplemented (P < 0.01) and placebo (P < 0.025) groups. The results indicate that zinc supplementation along with the diet would result in rapid restoration of zinc status, though there is no effect on the weight gain or other responses. PMID- 8365382 TI - Nutrient intake and biological maturation during adolescence. The Amsterdam growth and health longitudinal study. AB - The study evaluates the association of the food intake and the rate of biological maturation of 200 boys and girls in Amsterdam during their adolescence. The subjects were followed in a longitudinal survey over a period of 9 years, between the ages of 13 and 22 years. In the first four years (1976-1980) annual measurements were performed (school period). In 1985 a fifth measurement was made at the age of 21 years. Biological maturation was estimated from X-ray photographs of the left hand and wrist and rated according to the Tanner Whitehouse II method. On the basis of the annual measurements in the first four years a distinction was made between late maturers (LMs) and early maturers (EMs). The individual food intake was obtained with a cross-check dietary history method: a dietitian interviewed the entire range of foods and drinks, making allowance for regular meals as well as in-between meals, separately for normal schooldays and weekend days. Analysis of variance was used to test the effects of maturation (M), time of measurement (T) and interaction (M x T). The results show that EMs of both sexes consumed less energy and protein per kg body weight, but were fatter at young adult age and showed less habitual physical activity than LMs during the whole period of observation. The conclusion could be drawn that late maturation seems to coincide with an energy intake that is more appropriate to their higher activity pattern than early maturation during adolescence. This results in a significantly lower body fat mass in late maturing boys and girls compared to early maturers. PMID- 8365383 TI - 'Determination' of sugar alcohol and Polydextrose absorption in humans by the breath hydrogen (H2) technique: the stoichiometry of hydrogen production and the interaction between carbohydrates assessed in vivo and in vitro. AB - The production of hydrogen from substrates and substrate mixture of sugar alcohols and Polydextrose was determined, both in vivo using the breath hydrogen test, and in vitro, using human faecal microorganisms in anaerobic culture. One objective was to test a previous assumption that the stoichiometry of hydrogen production from different alternative carbohydrates is similar. Another objective was to discover whether hydrogen responses from mixtures of substrates were simply additive, or whether interactions occurred. The breath tests were performed in a 10 subject x 10 substrate factorial design with substrates and substrate mixtures (5-11 g) administered in 42 g chocolate confectionery. Incorporation of the alternative carbohydrates lactitol (L), Isomalt (I) and Polydextrose (P) into otherwise conventional confectionery increased breath hydrogen production by approximately 112, 73 and 11%/g respectively. There was no interaction between L and I or between P and I, but a combination of L and P approximately doubled the breath hydrogen anticipated from their individual contributions (P < 0.05). Anaerobic cultures showed a sixfold range in the efficiency of converting individual substrates and mixtures to hydrogen gas (0.003-0.018 kJ H2 per kJ carbohydrate). The positive interaction between L and P, and the lack of interaction between L and I, and between P and I, found in vivo were reproduced in vitro. The work showed that interpretation of the hydrogen breath test is confounded by differing stoichiometries for hydrogen production, by interaction between substrates and by an uncertain extent to which small intestinal hydrolysis yielding species with a fermentation stoichiometry that differs from the parent substrate. PMID- 8365384 TI - No effect of human serum and erythrocytes enriched in n-3 fatty acids by oral intake on Plasmodium falciparum blood stage parasites in vitro. AB - To examine the effect of n-3 polyunsaturated fatty acids (n-3 PUFA) on the erythrocytic growth of Plasmodium falciparum, serum and erythrocytes were separated from blood of a healthy donor before and after he had taken fish oil capsules for 8 days. Such intake supplied an amount of eicosapentaenoic acid (EPA, 20:5n-3) of 3.5 g/d and docosahexaenoic acid (DHA, 22:6n-3) of 2.5 g/d and 24 mg/d of total tocopherol. Post-intake fish oil serum (post-s) and erythrocytes (post-e) were tested in vitro for inhibitory activity against blood stages of P. falciparum compared with pre-intake serum (pre-s) and pre-intake erythrocyte (pre e). Also the effect of EPA and arachidonic acid (AA, 20:4n-6) on the erythrocytic growth of P. falciparum was tested using in vitro assays. The results show that both post-s and post-e had no antimalarial activity on P. falciparum. No differential antimalarial effect was observed for 20:5n-3 compared with 20:4n-6, which at high concentrations (> 40 microM) had an anti-schizont-growth effect. PMID- 8365385 TI - Effects of stearic acid and trans fatty acids versus linoleic acid on blood pressure in normotensive women and men. AB - The objective of this study was to compare the effect of linoleic acid (cis,cis C18:2) with that of its hydrogenation products stearic acid (C18:0) and elaidic acid (trans-C18:1) on blood pressure levels in normotensive humans. We therefore measured the effects of these fatty acids on systolic and diastolic blood pressure in 30 women and 25 men. Three strictly controlled experimental diets were supplied to every subject for 3 weeks each, in different order (multiple cross-over). The composition of the three diets was constant, except for 8% of daily energy, which was provided by either linoleic acid, stearic acid, or monounsaturated trans fatty acids. The statistical power for detecting a true difference between two diets of 3 mmHg in systolic and diastolic blood pressure was over 90%. Mean systolic/diastolic blood pressure at the end of the dietary periods was 114/69 mmHg on the linoleic acid diet, 113/70 on the stearic acid diet, and 113/69 on the trans fatty acid diet. No significant differences were observed in blood pressure levels after 3 weeks on each diet. We conclude that a major increase in the intake of linoleic acid at the expense of stearic acid or trans fatty acids has no effect on blood pressure in normotensive young women and men. PMID- 8365386 TI - Computerized analysis of food records: role of coding and food composition database. AB - Reported dietary intake records of 30 subjects (26 men and 4 women) were analysed by three different centres using their own computerized nutrient database systems. The agreement between systems was evaluated by different statistical criteria (the correlation coefficient, the mean difference and the proportion of individuals placed in the same thirds of distribution). Significant differences between the three systems were found in the calculation of alcohol, polyunsaturated fatty acids, saturated fatty acids, linoleic acid, linolenic acid, cholesterol, magnesium, sodium and water. To ascertain the extent of mean differences that could be attributed to the coding process or to the database used, coding forms of each centre were forwarded to the other two centres. Analysis of variance showed that differences in the data obtained by the three systems were mainly due to the food composition database used. PMID- 8365388 TI - Visual/vestibular effects of inert gas narcosis. AB - Divers breathing compressed air at depths beyond 30 m experience a type of behavioural impairment known as inert gas narcosis. This condition degrades performance on a wide range of tasks and has the potential to compromise safety. Symptoms associated with narcosis include slowed response time, amnesia, and euphoria. Studies have also found disturbances to mechanisms regulating ocular control in response to vestibular stimulation; however, these experiments have been limited to very low frequency head movement (0.2 Hz). Thus, to further examine the effects of narcosis on visual/vestibular mechanisms, the vestibular ocular reflex (VOR) was assessed across a range of higher frequencies more representative of natural head movement (2.0-4.7 Hz). Seven subjects were tested prior to, during and after exposure to narcosis which was induced using 30% nitrous oxide. Standard room air was breathed as a control. The results indicated that narcosis decreased the velocity of compensatory eye movements in response to head rotation (decrease in VOR-gain), with more pronounced decreases occurring at the higher frequencies. The lag between eye and head position (phase lag) was also decreased by nitrous oxide; an effect that was again more pronounced at higher frequencies. These results indicate that narcosis disrupts ocular regulatory mechanisms which help to stabilize images on the retina during head movement. PMID- 8365387 TI - Work-related chronic injuries of the forearm and hand: their specific diagnosis and management. AB - Work-related chronic injuries occur in muscles, tendons, and nerves. Epidemiological, histological, and physiological data confirm their often disputed physical basis. Terms such as repetitive strain injury and cumulative trauma disorder, when used as a diagnosis, have obscured the issue for they are really statements of causation. Definitive diagnosis is required both to treat and prevent such injuries. Precise terminology that identifies the tissue and its pathology is required. A detailed assessment methodology is described that allows a precise diagnosis. A clear relationship to work stress is necessary both to establish the cause and formulate prevention strategies. Treatment must begin early and be appropriate to the tissue and the nature of the injury. Examples are presented and discussed. Early treatment begins before too much damage has been done and yields better results. PMID- 8365390 TI - The vibration characteristics of chain saws and their influence on vibration white finger disease. AB - The vibration from chain saws can cause vibration-induced white finger disease (VWFD). Measurements of vibration levels on the front and rear handles of different chain saw-types, and on the operator's middle finger were collected at three logging camps on Vancouver Island. Factors effecting the vibration levels on the finger and handles were investigated. The acceleration at the firing frequency was found to be the dominant factor effecting handle and finger vibration. Other factors which were investigated were: grip force; the presence of handle covers; and chain sharpening procedure. Weighted acceleration levels are calculated and this information is used to assess the latency period for fallers to develop VWF disease. PMID- 8365389 TI - Biomechanical comparison of carpet-stretching devices. AB - Peak impact forces, measured from seven male carpetlayers using a knee-kicker over 39 trials were 2933 N (SD 397), taking 9.5 ms (SD +/- 1.1) to reach peak. The knee-kicking cycle involved high knee decelerations of 880 m.s-2 (SD +/- 271). Angles at peak force for the knee (63 degrees SD +/- 10 degrees) and hip (80 degrees SD +/- 35 degrees) showed considerable variation between individuals. Kneeling forces on the non-kicking leg during the kick cycle were 894 N: comparative forces were 368 N and 476 N measured during use of the power stretcher and crab re-stretcher, respectively. Under dynamic conditions the effective mechanical advantage of the knee-kicker was less than 1.0. In comparison, the mechanical advantage of the power stretcher was approximately 14 times greater over the stretch action. When tested with a crab re-stretcher, the breaking strength of the smooth-edge to which the carpet attaches averaged 2384 N (SD +/- 245). Design guidelines for an improved carpet stretching device are provided. PMID- 8365391 TI - A human factors evaluation of two different machine control systems for log loaders. AB - The implement movement in today's mobile, heavy machinery does not correspond in a one-to-one proportion with hand control movement. This lack of correspondence places high perceptual and psychomotor demands on the operator. The objective of this study was to evaluate the human factors of two different machine control systems on a log loader in a controlled field setting. The traditional joint control system was compared with a co-ordinated control system. The two machines were tested on ten novice and six experienced operators. Operator performance was based on the time required to complete a task sequence, as well as reaction time. The results show that the novice operators performed significantly better in co ordinated mode than they did in joint mode, whereas the experienced operators performed better in joint mode than they did in co-ordinated mode. Results indicate, however, that it would not take long for experienced operators to transfer their skills from joint control to co-ordinated control. PMID- 8365392 TI - Cardiovascular and muscular strain during a tree planting season among British Columbia silviculture workers. AB - Cardiovascular and muscle strain were determined in 16 British Columbia reforestation workers during a period of tree planting (75 days). Serial data collected from each worker included pre- and post-work blood chemistry on the first day of the work shift; working heart rate (HR), a PWC170 fitness test, and a daily diary of an individual's work-rest schedule. Repeated blood samples from each planter were analysed for the elevated serum enzyme activities (ESEA) of creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate transaminase (AST), and for the blood haematology parameters (BH) of haematocrit (Hct), red blood cell count (RBC), and haemoglobin (Hgb). HR and BH were used as an index of cardiovascular strain and ESEA was used as an index for musculoskeletal strain. A group mean working heart rate of 116.5 +/- 9 b.min-1 (range 100.0-139.1) was sustained throughout the period of an 8.0 hour day representing 39.2% of the delta Heart Rate ratio (ratio of elevated working Hr above resting to maximum HR). Grouped data were analysed by sample day for a subset of planters (n = 10) participating in six sample dates during the first 32 days of planting. Pre- and post-work ESEA were significantly higher throughout the entire planting period when compared with a pre-season resting control group (n = 9, p < or = 0.01). The post-work rise in CK and AST from pre-work values decreased during successive weeks of work as some adaptation to the work rate occurred. LDH continued to rise and was significantly elevated on day 32 compared with day 1. No significance was found in the BH variables between sample dates, yet a decreasing trend was observed. However, pooled data from all subjects for all sample dates showed a highly significant difference (p < or = 0.01) between pre- and post-work samples for both ESEA and BH. ESEA increased and BH decreased. These data present evidence that the work rate and rest time of a tree planter are not well ordered within the daily and seasonal working routine, and may compromise worker well being in the silviculture industry. PMID- 8365393 TI - Physiological effects of work stress and pesticide exposure in tree planting by British Columbia silviculture workers. AB - Tree planters in British Columbia have reported symptoms that are congruent with musculoskeletal stress and organophosphate or carbamate pesticide intoxication. The purpose of this research was to determine the existence of any physiological or biochemical correlate supporting the existence of these potential hazards in tree planting. Worker's health complaints were assessed from regularly distributed questionnaires. Blood samples were obtained from 14 male and three female Canadian subjects before and after tree planting work on 10 occasions throughout a tree planting season. The strenuous physical challenge of tree planting was confirmed by a significant elevation of serum enzyme activity (ESEA) at the beginning of the season, which did not return to a normal level during the remainder of the season. Significant (p < or = 0.05) inhibition of erythrocyte acetylcholinesterase activity (AChE) postwork was observed in 15.9% of individuals, and a significant group mean prework-postwork difference of AChE or plasma pseudocholinesterase (PChE) was observed on two days of testing, indicating a potential toxicological hazard from pesticide absorption. No correlation was found between the degree of ESEA or cholinesterase inhibition and the number of health complaints. PMID- 8365394 TI - Ergonomics aspects of tree-planting using 'multipot' technology. AB - The highlights of a descriptive study on the ergonomics and occupational health and safety aspects of tree-planting in Quebec are presented. The study was planned to consider the most representative geographical sites, planting technologies, and planting organizations. Semi-directed interviews were made with a mixed group of 48 male and female tree-planters and physiological measurements were made on four male planters. Tools and other equipment were also examined. An analysis of the work identified the main elements of the planting cycle, and the high cardiac rate in the working planters was related more to his manual transportation of seedlings and travel on rough paths than to planting per se. A tree-planter will typically travel 2.4 km carrying 16.8 kg of material and equipment in order to plant an average of 1245 seedlings daily. One out of two interviewed planters reported having a work-related accident or incident during his or her lifetime planting career. The body parts reported most frequently injured were the lower extremities (knee, foot, ankle), the skin, the eyes, and the wrist. Recommendations on the development of appropriate tools and footwear for tree-planters and for further research on repetitive strain injury induced by tree-planting have been made. PMID- 8365395 TI - The anatomy of a kinase and the control of phosphate transfer. PMID- 8365396 TI - Zinc coordination in mammalian sorbitol dehydrogenase. Replacement of putative zinc ligands by site-directed mutagenesis. AB - Rat sorbitol dehydrogenase was expressed in Escherichia coli and purified to homogeneity, resulting in a protein with a specific activity of 4.7 U/mg, close to that of the enzyme isolated from mammalian liver. A Glu residue has been postulated to replace the Cys of alcohol dehydrogenase as a ligand to the active site zinc atom of sorbitol dehydrogenase. This Glu (position 155 in the rat enzyme) was mutated both to Cys, in order to mimic the alcohol dehydrogenase relationships, and to Ala, as a control. A third mutation, Cys164 to Ala, was also performed since Cys has also been considered as a possible zinc ligand. With Ala at position 155, an inactive enzyme was obtained, showing that correct active site relationships have been destroyed. With Cys at position 155, the enzyme is still partly active, but rapidly looses activity unless stabilized by the addition of ZnSO4. The catalytic efficiency in the oxidation of sorbitol is 120 fold less than that of the native form, and reduction of fructose is lost completely. In contrast, the activity of the Cys164Ala mutant is comparable with that of the native enzyme and, in fact, even increased in the oxidation of sorbitol. Combined, the results strongly suggest that Glu155 is a ligand to the active-site zinc atom. Zinc analysis of the different variants of sorbitol dehydrogenase establishes that all contain one atom of zinc/subunit, also when the catalytic function is lost. Apparently, zinc remains coordinated even after replacement with an amino acid residue (Ala) unable to ligand metal atoms. PMID- 8365397 TI - Intestinal arginine metabolism during development. Evidence for de novo synthesis of L-arginine in newborn pig enterocytes. AB - The capacity for L-arginine metabolism was studied in villus enterocytes isolated from pigs at birth, after 2-8 days suckling and after weaning. Immediately after birth, enterocytes were able to convert 1 mM L-citrulline, 2 mM L-glutamine or 1 mM L-ornithine to L-arginine. In 2-8-day-old animals, the net production of L arginine from L-citrulline (2.00 +/- 0.45 nmol x 10(6) cells-1 x 30 min-1), or from L-ornithine (0.29 +/- 0.06 nmol x 10(6) cells-1 x 30 min-1) was similar to the values obtained at birth. Furthermore, 40% of L-arginine synthetized de novo from L-citrulline were released into the incubation medium. In 2-8-day-old animals, the production of L-arginine from L-glutamine represented only 5% of the production at birth (the latter being 0.73 +/- 0.15 nmol x 10(6) cells-1 x 30 min 1). In enterocytes isolated from post-weaned pigs, no significant production of L arginine from either L-glutamine or L-ornithine was detected. In contrast, although the L-arginine production from L-citrulline was very low in post-weaned animals, it was significantly enhanced in the presence of L-glutamine, representing 23% of the production measured in suckling animals. The capacity of enterocytes to cleave L-arginine to L-ornithine and urea was very limited at birth, but was increased more than threefold in 2-day-old animals. This was concomitant with a marked increase in arginase activity. In post-weaned animals, the flux through arginase in intact enterocytes, and the arginase activity were both threefold higher than in 2-8-day-old animals. It is concluded that enterocytes isolated from neonatal pigs exhibit the capacity for a net production of L-arginine since the metabolism of this amino acid is oriented to anabolism rather than catabolism. The results are discussed in relation to L-arginine metabolism in the neonatal liver. PMID- 8365398 TI - The major-histocompatibility-complex-encoded beta-type proteasome subunits LMP2 and LMP7. Evidence that LMP2 and LMP7 are synthesized as proproteins and that cellular levels of both mRNA and LMP-containing 20S proteasomes are differentially regulated. AB - The proteasome (high-molecular-mass multicatalytic proteinase complex) is composed of a large number of non-identical protein subunits of the alpha and beta types. The mouse beta-type subunits LMP2 and LMP7 (LMP, low-molecular-mass protein) are encoded within the mouse major histocompatibility complex (MHC II) region, and are thought to connect the proteasome to the MHC class-I antigen processing pathway. In the present communication, we have analysed the two proteasome subunits with regard to their identity within the proteasome complex, their protein levels, their amounts of mRNA in different mouse tissues and cell lines, and have investigated the intracellular localization of LMP2 and LMP7 subunits in thymus and liver by immunocytology. Our experiments indicate that LMP2 and LMP7 subunits are synthesized as precursor proteins of 24 kDa and 30 kDa, respectively, and that only the processed 21-kDa and 23-kDa subunits are part of the 20S proteasome complex. The proportion of LMP2-subunit-containing and LMP7-subunit-containing proteasome complexes, as well as LMP2 and LMP7 mRNA levels, vary strongly and are shown to be dependent on the tissues or cell lines analysed. Furthermore, high LMP2 and LMP7 mRNA levels do not always correlate with high protein levels, suggesting a specific translational mechanism which controls proteasome subunit synthesis. Generally, mRNA levels appear to be particularly high in those tissues which are known to be involved in MHC class-I antigen presentation. Immunocytological analysis shows a strong nuclear localization of the subunits in cells of the thymus, while in the liver they appear to be evenly distributed between the two cellular compartments. Our data support the idea that both LMP2 and LMP7 proteins are non-essential proteasome subunits which are probably involved in the regulation of proteasome activities. The function of the two subunits, however, may not be restricted to the proposed role of proteasomes in antigen presentation. PMID- 8365399 TI - Regulation of rabbit alpha 1-acid glycoprotein gene expression in acute-phase liver. Identification of inducible and constitutive proteins like CCAAT-enhancer binding protein that interact with the 5'-proximal promoter elements. AB - To identify the cis-acting DNA sequences responsible for inducible transcription of rabbit alpha 1-acid glycoprotein gene, 5'-flanking region containing 529 bp of this gene and its various 5'-deletions were linked to the reporter gene coding for the bacterial chloramphenicol acetyltransferase (CAT) and analyzed for their ability to confer cytokine-mediated inducibility to the reporter CAT gene in liver cells. Deletion analysis has identified a 151-bp region from the sequence 186 to -35, that contains the regulatory promoter element(s) responsible for stimulation mediated by cytokines present in the conditioned-medium. Using mobility shift assays, we have identified highly inducible nuclear factors in acute liver nuclear extract that interact with this regulatory promoter region. DNase I footprint analysis has revealed two adjacent nuclear factor binding sites and competition of DNA-binding activity has indicated that the distal element of these two sites has higher affinity for nuclear factors than the proximal one. Both of these two regions have been found to be capable of directing conditioned medium-induced transcription. Studies on the characterization of nuclear factors binding to these elements have shown that they belong to a class of transcription factors called CCAAT-enhancer binding protein (C/EBP). Our results indicate that binding of C/EBP-like factors to the inducible promoter elements of rabbit alpha 1-acid glycoprotein gene is highly specific and the induction of this gene under acute-phase conditions may involve their participation. PMID- 8365401 TI - Secondary structure of the DNA-binding domain of the c-Myb oncoprotein in solution. A multidimensional double and triple heteronuclear NMR study. AB - The DNA-binding domain of the c-Myb oncoprotein contains two repeats, R2 and R3, both of which have been proposed to be related to the helix-turn-helix (HTH) motif. As a first step towards determination of the three-dimensional structure of this domain and of the mode of interaction with the DNA, we have undertaken multidimensional heteronuclear NMR studies using uniformly 15N-labeled and 13C, 15N double-labeled R2R3 and, a selectively 15N-enriched sample on all lysine, histidine and leucine residues of R2R3. We present almost complete assignments of the backbone 1H, 15N and 13C" atoms and determine the secondary structure of R2R3 in solution. The R3 repeat is composed of three helices (residues 62-75, 78-85 and 91-100) while for the R2 repeat only two helices are found (residues 10-23 and 28-34). The remaining C-terminal part of the R2 repeat, predicted to be helical and part of the HTH motif, undergoes intermediate conformational exchange processes. Stabilization of this segment might occur upon binding to DNA. PMID- 8365400 TI - Role of Tyr201 and Tyr385 in substrate activation by p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. AB - The crystal structure of the enzyme-substrate complex of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens shows that the hydroxyl group of 4 hydroxybenzoate interacts with the side chain of Tyr201, which is in close contact with the side chain of Tyr385. The role of this hydrogen bonding network in substrate activation was studied by kinetic and spectral analysis of Tyr-->Phe mutant enzymes. The catalytic properties of the enzymes with Tyr201 or Tyr385 replaced by Phe (Tyr201-->Phe and Tyr385-->Phe) with the physiological substrate are comparable with those of the corresponding mutant proteins of p hydroxybenzoate hydroxylase from P. aeruginosa [Entsch, B., Palfey, B. A., Ballou, D. P. & Massey, V. (1991) J. Biol. Chem. 266, 17341-17349]. Enzyme Tyr201 ->Phe has a high Km for NADPH and produces only 5% of 3,4 dihydroxybenzoate/catalytic cycle. Unlike the wild-type enzyme, the Tyr201-->Phe mutant does not stabilize the phenolate form of 4-hydroxybenzoate. With enzyme Tyr385-->Phe, flavin reduction is rate-limiting and the turnover rate is only 2% of wild type. Despite rather efficient hydroxylation, and deviating from the description of the corresponding P. aeruginosa enzyme, mutant Tyr385-->Phe prefers the binding of the phenolic form of 4-hydroxybenzoate. Studies with substrate analogs show that both tyrosines are important for the fine tuning of the effector specificity. Binding of 4-fluorobenzoate differentially stimulates the stabilization of the 4 alpha-hydroperoxyflavin intermediate. Unlike wild type, both Tyr mutants produce 3,4,5-trihydroxybenzoate from 3,4 dihydroxybenzoate. The affinity of enzyme Tyr201-->Phe for the dianionic substrate 2,3,5,6-tetrafluoro-4-hydroxybenzoate is very low, probably because of repulsion of the substrate phenolate in a more nonpolar microenvironment. In contrast to data reported for p-hydroxybenzoate hydroxylase from P. aeruginosa, binding of the inhibitor 4-hydroxycinnamate to wild-type and mutant proteins is not simply described by binary complex formation. A binding model is presented, including secondary binding of the inhibitor. Enzyme Tyr201-->Phe does not stabilize the phenolate form of the inhibitor. In enzyme Tyr385-->Phe, the phenolic pKa of bound 4-hydroxycinnamate is increased with respect to wild type. It is proposed that Tyr385-->Phe is involved in substrate activation by facilitating the deprotonation of Tyr201. PMID- 8365402 TI - Evidence for transformation-related increase in CTP synthetase activity in situ in human lymphoblastic leukemia. AB - To determine the role of the enzyme CTP synthetase (EC 6.3.4.2) in the synthesis in situ of CTP in normal and in malignant lymphoblastic cells, the metabolism of radiolabeled pyrimidine ribonucleosides was studied in proliferating normal T lymphocytes and was compared with that of proliferating MOLT-3 cell-line cells and differentiated (non-proliferating) MOLT-3 cells. Both the incorporation of [14C]uridine into UTP and CTP and the incorporation of [14C]cytidine in CTP, as well as the fluxes of these labeled nucleosides through the nucleotide pools into nucleic acids, were elevated in proliferating MOLT-3 cells compared to proliferating T lymphocytes. Furthermore, the conversion of UTP into CTP was enhanced in proliferating MOLT-3 cells compared to proliferating T lymphocytes, indicating a higher activity of CTP synthetase in the leukemic cells. In non proliferating MOLT-3 cells, the pyrimidine ribonucleotide fluxes were decreased compared to proliferating MOLT-3 cells and proliferating T lymphocytes. However, the decreased ratio of uracil/cytosine ribonucleotides that was found in proliferating T lymphocytes and proliferating MOLT-3 cells compared to non proliferating blood lymphocytes, was preserved in the differentiated MOLT-3 cells. Moreover, although the fluxes had decreased, most CTP was still synthesized by CTP synthetase in the differentiated MOLT-3 cells. Thus, the elevated activity of CTP synthetase in MOLT-3 cells was independent of the cell growth and maturation stage. We conclude that the increased activity of CTP synthetase is associated with the process of malignant transformation in MOLT-3 cells. Therefore, CTP synthetase offers an attractive target for selective therapy in human acute T-lymphoid leukemia. PMID- 8365403 TI - Secretory phospholipase A2 is not required for arachidonic acid liberation during platelet activation. AB - The subcellular localization of secretory phospholipase A2 (sPLA2) and cytosolic phospholipase A2 (cPLA2) in resting and activated platelets, and their involvement in arachidonic acid liberation during platelet activation, were studied. The amounts of sPLA2 and cPLA2 recovered were not modified during platelet activation. sPLA2 was mainly associated with the organelles of resting platelets (71% of total activity) and was released into the extracellular medium during cell activation (60% of total activity), whereas the majority of cPLA2 was localized in the cytosol of resting and activated platelets. The secretion of sPLA2 correlated with the release of ATP. sPLA2-depleted platelets aggregated as much as control platelets and produced similar amounts of thromboxane B2 upon thrombin activation. These results indicate that sPLA2 is not involved in the liberation of arachidonic acid during platelet activation. PMID- 8365404 TI - Restriction-enzyme cleavage of DNA modified by platinum(II) complexes. AB - The effect of binding of cis-diamminedichloroplatinum(II), its trans isomer and diethylenetriaminechloroplatinum(II) chloride to DNA on the splicing effectiveness of BamHI, EcoRI and SalI restriction endonucleases has been determined by means of gel electrophoresis. All three platinum complexes inhibit the cleavage of linearized plasmid DNA. In addition, the three platinum complexes bound to DNA constitute a barrier across which the linear diffusion of EcoRI on DNA is difficult. We interpret these findings to mean that the splicing effectiveness of restriction enzymes is influenced by bifunctional and monofunctional DNA adducts of platinum via both steric interference and DNA conformational distortions. Whereas the platinum adducts in the restriction sites or in their very close proximity inhibit the cleavage, the lesions occurring a greater distance from the restriction site can slow down the process of the localization of recognition sequences. PMID- 8365405 TI - VAT-1 from Torpedo electric organ forms a high-molecular-mass protein complex within the synaptic vesicle membrane. AB - VAT-1 is an abundant 41-kDa protein from Torpedo cholinergic synaptic vesicles. Most of VAT-1 immunoreactivity (70%) is localized to the synaptic vesicle membrane while the rest (30%) copurifies with larger membranous fragments. VAT-1 forms a high-molecular-mass complex within the synaptic vesicle membrane. The Stokes radius of the VAT-1 complex is 4.85 nm and the sedimentation coefficient is 8.0 x 10(-13) S. Using these values, the calculated apparent mass of the VAT-1 complex is 176 kDa and the friction coefficient is consistent with that for a globular protein. Electrophoresis of solubilized synaptic vesicle proteins following cross-linking resulted in a 40-kDa ladder which was detected by VAT-1 antibodies. This is in accord with VAT-1 protein complex being composed primarily of VAT-1 subunits. The hydrodynamic characteristics of the VAT-1 protein complex suggest that it is composed of three or four VAT-1 subunits. Synaptophysin, an abundant component of Torpedo synaptic vesicle membranes, which has a similar apparent size as VAT-1, is not part of the VAT-1 protein complex. Interactions between the subunits within the protein complex do not depend on disulfide bonds or on lowering the ionic strength. However, partial dissociation of VAT-1 subunits from the complex occurs by chelating calcium ions. PMID- 8365406 TI - High expression in Escherichia coli of the gene coding for dihydrofolate reductase of the extremely halophilic archaebacterium Haloferax volcanii. Reconstitution of the active enzyme and mutation studies. AB - The gene coding for the enzyme dihydrofolate reductase of the extremely halophilic archaebacterium Haloferax volcanii was recombined into the Escherichia coli expression vector pET11d. Following induction, the enzyme was produced in large quantities and accumulated in the cells in an insoluble form. The enzymic activity could be efficiently reconstituted by dissolving the aggregate in 6 M guanidine hydrochloride followed by dilution into salt solutions. Mutants were produced in which Lys30 was converted to Leu (K30L), Lys31 was converted to Ala (K31A) and a double mutant in which both lysines were converted (K30L, K31A). The mutated enzymes were produced in E. coli, activated and purified to homogeneity. The effect of the salt concentration on the steady-state kinetic parameters was determined. It was found that the salt concentration affects the Km but not kcat of the various mutants. PMID- 8365407 TI - The solution structure of the histidine-containing protein (HPr) from Staphylococcus aureus as determined by two-dimensional 1H-NMR spectroscopy. AB - The three-dimensional solution structure of the heat-stable phosphocarrier protein HPr from Staphylococcus aureus was determined from two-dimensional NMR data by restrained molecular dynamics. It consists of a large twisted antiparallel beta-pleated sheet with four strands A, B, C, and D of amino acids 2 7, 34-37, 40-42 and 60-65. Three right-handed helices A, B, C (amino acids 18-27, 47-53 and 71-85) are positioned on top of this sheet. The aromatic ring of His15 is located in a cleft formed by amino acids 12-17 and 55-58, only the nitrogen (N delta 1) atom which can be phosphorylated by enzyme I is exposed to the water. The side chains of Thr12 and Arg17 are located close to the histidine ring. The regulatory serine residue (Ser46) is located in a hydrophobic patch, its hydroxyl group is water-accessible but forms hydrogen bonds with the amide groups of the backbone. The general features of the three-dimensional structure are similar to those found in HPr proteins from different microorganisms such as Escherichia coli, Bacillus subtilis and Streptococcus faecalis. PMID- 8365408 TI - Comparative study of high-mannose-type oligosaccharides in membrane glycoproteins of rat hepatocytes and different rat hepatoma cell lines. AB - A comparative study was undertaken to characterize the oligosaccharides released by endo-beta-N-acetylglucosaminidase H (endo H) from the membrane glycoproteins of rat hepatocytes and three different Morris hepatoma cell lines (NA-MH 7777, HTC and MH1C1). It is shown that the membrane glycoproteins of hepatocytes and hepatoma cells contain markedly different quantities and forms of high-mannose type carbohydrate chains. After radiolabelling of the cells with D-[2-3H]mannose, in the absence and presence of 1 mM 1,5-dideoxy-1,5-imino-D-mannitol (1 deoxymannojirimycin), high-mannose-type oligosaccharides were released from delipidated membrane glycoproteins by enzymic digestion with endo H. The carbohydrate chains were converted to their corresponding oligosaccharide alditols by reduction with sodium borohydride, then further analysed by HPLC using an APS-2 Hypersil column. In the absence of 1-deoxymannojirimycin, up to 10% of the radiolabelled oligosaccharides were released by endo H-treatment of the membrane glycoprotein fraction from rat hepatocytes. In contrast, the quantity of radiolabelled high-mannose-type carbohydrate chains released by endo H-treatment from tumour-cell membrane glycoproteins of hepatoma cell lines NA-MH 7777 (31.5%). MH1C1-MH 7795 (37.2%) and HTC-MH 7288c (48%) was increased up to fivefold. The formation of higher-mannosylated structures after oligosaccharide analysis was observed in all hepatoma cell lines, with Man8GlcNAcOH as the major component, whereas in hepatocytes Man5GlcNAcOH was the predominant high-mannose type structure. In contrast, in the presence of the Golgi alpha-D-mannosidase I inhibitor, 1-deoxymannojirimycin, no significant differences were observed between the distribution of high-mannose-type oligosaccharides in the membrane glycoproteins of hepatocytes and hepatoma cells. However, in the presence of this inhibitor, the proportion of radiolabelled glycans sensitive to deglycosylation by endo H was greatly increased (> 85%) in all the cell lines investigated, the predominant structures being Man8-9-GlcNAcOH. This study shows that an increased content of high-mannose-type sugar chains is a general characteristic of membrane bound glycoproteins for malignant transformed hepatocytes. PMID- 8365409 TI - The role of the proton-pumping and alternative respiratory chain NADH:ubiquinone oxidoreductases in overflow catabolism of Aspergillus niger. AB - Mitochondria of fungi contain two respiratory chain enzymes concerned with the oxidation of matrix NADH. These are the proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, which has a high affinity for NADH, and a non-proton-pumping NADH:ubiquinone oxidoreductase, called alternative NADH dehydrogenase, which has a low affinity for NADH. The role of these two enzymes in normal and overflow catabolism has been studied in Aspergillus niger. Three strains were investigated, the wild-type 732, the mutant nuo51 that was generated from the wild-type by disrupting the gene of the (51-kDa) NADH-binding subunit of complex I and the citric acid over-producing strain B60 that looses complex I concomitantly with the onset of the over-production. Under standard growth conditions, respiratory energy transduction in the mutant nuo51 was decreased by 40% compared to the parental wild-type and the strain B60. Respiratory electron transfer in the mutant nuo51, however, meets standard catabolic requirements. The intracellular levels of citric acid cycle intermediates in the mutant nuo51 were the same as in the other two strains. Under growth conditions which lead to uncontrolled catabolic flux through glycolysis, a dramatic catabolic overflow occurred in the mutant nuo51. Intracellular levels of citric acid cycle intermediates increased to 20-fold normal levels. The strain B60, likewise lacking complex I under these conditions, excretes large amounts of citrate to moderate the intracellular catabolic overflow. PMID- 8365410 TI - Recombinant soluble human interleukin-6 receptor. Expression in Escherichia coli, renaturation and purification. AB - The recombinant soluble human interleukin-6 receptor (srhIL-6R) was expressed in Escherichia coli as a non-glycosylated protein comprising the first 339 amino acids after the signal peptide. The protein accumulated within the cells as insoluble protein aggregates (inclusion bodies). After solubilization, 10% of the denatured srhIL-6R could be renaturated by an in vitro folding procedure using L arginine and the glutathione-redox system. The native receptors were purified to near homogeneity by affinity chromatography on an IL-6-Sepharose column. The functional features of the recombinant soluble receptor were further analysed. A part of the extracellular domain (amino acids 145-345) of the human interleukin-6 receptor (IL-6R) was expressed in E. coli and the purified protein was used to raise antibodies in rabbits. Characterization of the antiserum obtained indicated that an epitope of 13 amino acids close to the transmembrane region is needed for recognition by the antibodies. Since the antiserum obtained did not interfere with IL-6 binding, it could be used to establish a cell-free IL-6-binding assay, In this assay, the srhIL-6R bound IL-6 with an affinity of Kd = 1.5 nM as measured by Scatchard-plot analysis. When 125I-IL-6 was chemically cross-linked to the purified srhIL-6R and analyzed by SDS/PAGE, several 125I-IL-6-containing bands were detected, indicating the possible existence of a multimeric structure of the natural IL-6/IL-6R complex. The srhIL-6R was shown to exhibit biological activity, i.e. it stimulated acute-phase protein synthesis in the recently established human hepatoma cell line HepG2-IL-6 which does not express the IL-6 binding subunit of the IL-6R complex on the cell surface. PMID- 8365411 TI - Rabbit and rat liver nuclei both contain proteins which bind to the regions controlling apolipoprotein A-I gene expression. AB - We have tested the 5' flanking region of the apolipoprotein A-I (apo A-I) gene, which controls its expression in hepatic cells, for the ability to bind protein factors from rat and rabbit liver nuclei. We found that nuclear extracts from each species contain proteins which bind to three sites in the region which have been shown to be important for control of apo A-I gene transcription. These results contrast with a previous report [Dai, P. H., Lan, S. S. F., Ding, X. H. & Chao, Y. S. (1990) Eur. J. Biochem. 190, 305-310] that no rabbit liver nuclear protein could be detected which binds to the rat apo A-I upstream region and that this lack of binding could explain the failure of the rabbit liver to express the apo A-I gene. We have also shown that the low levels of apo A-I mRNA in the rabbit liver correlate with decreased transcription. Our data suggest that the lack of apo A-I gene expression in liver is a result of transcriptional control but cannot be due to simple lack of protein binding to this region of DNA. PMID- 8365412 TI - Expression of the laminin-A chain is down-regulated by a non-canonical polyadenylation signal. AB - It is well accepted that 3' untranslated regions (UTR) are an essential part of mRNA. However, little is known in detail about the contribution of different regions of 3' UTR on synthesis, stability and translatability of their mRNA. In addition to the highly conserved hexanucleotide AAUAAA, some consensus sequences for 3'-end processing and polyadenylation have been characterized, but most of this work has been done with viral mRNA or beta-globin mRNA. We have studied the influence of the 3' UTR of the mRNA for the three chains A, B1, B2 of laminin on the expression of a reporter gene (galK). Laminin is a large glycoprotein of basement membranes and all three polypeptide chains are needed in equal amounts for a functional molecule. The three 3' UTR of the laminin mRNA differ widely with respect to length, number of polyadenylation signals and other consensus sequences. Nevertheless, all three 3' UTR reduce the expression of the reporter gene at least three-fold, when the corresponding cDNA sequences are inserted downstream of the reporter gene instead of the 3' UTR of simian virus 40 early genes. The 3' UTR of laminin-A mRNA contains the non-canonical polyadenylation signal AUUAAA which seems to be responsible for the limiting amounts of laminin-A mRNA and protein compared to those for laminin B1 and B2 [Speth and Oberbaumer (1993) Exp. Cell Res. 204, 302-310]. Mutation of the laminin-A polyadenylation signal to the canonical form AAUAAA increases expression by a factor of 2.5. PMID- 8365413 TI - Large-scale preparation of fully deuterated cell components. Ribosomes from Escherichia coli with high biological activity. AB - Some applications of NMR and of neutron scattering require fully deuterated biological material which should be highly active and available in large quantities. These requirements are hardly compatible since full deuteration is achieved easily only if cells are grown in minimal media. This condition used in standard batch fermentation results in both low yields and reduced activities of the biological mass. Here we report a method which combines the apparently incompatible requirements taking advantage of a recent observation according to which the appearance of growth inhibiting extracellular products could be prevented. The method was applied for growing Escherichia coli cells, strain MRE600rif (resistance against high doses of rifampicin is used as selection marker) on partially deuterated media (76% and 84% D2O) with glucose as carbon source and on deuterated acetate and succinate with 100% D2O when full deuteration was to be achieved. The essential point for preserving the log-phase character of the cells is that the cultivation is carried out at substrate limiting conditions thus keeping the growth rate at low levels (for glucose the growth rate, mu < or = 0.35 h-1, for acetate/succinate mu < or = 0.1 h-1) which avoids the accumulation of the substrate or of by-products in the medium. Our data suggest that acetate is a main extracellular component for accompanying or triggering the transition from logarithmic growth to stationary phase of E. coli cells cultivated on glucose as carbon source. The cells were first grown in fed batch to high cell densities (above 50 g wet cells/l) under conditions of substrate limitations. A steady-flow fermentation followed keeping the growth rate at about mu of 0.1 h-1. Cells were harvested in kg quantities, the extracted ribosomes showed a normal complement of proteins, contained intact rRNA and were fully active. The ribosomal protein and rRNA fractions could be efficiently reconstituted to highly active particles. In the case of full deuteration a matching point of 120% (tentative D2O scale) was achieved. The reported method facilitates the preparation of deuterated biological material for applications in NMR and neutron scattering analysis. PMID- 8365414 TI - Isolation and identification of two proto-oncogene products related to c-fgr and fyn in a tyrosine-protein-kinase fraction of rat spleen. AB - TPK-III, a tyrosine-protein-kinase fraction previously isolated from rat spleen [Brunati, A. M. & Pinna, L. A. (1988) Eur. J. Biochem. 172, 451-457] has been further purified and resolved by Mono-Q FPLC into two homogeneous compounds, Q1 and Q2, with molecular mass approximately 52 kDa, exhibiting high specific activities for phosphate incorporation into the phosphoacceptor substrate poly(Glu80Tyr20) (1194 nmol.min-1 x mg-1 and 579 nmol.min-1 x mg-1, respectively). Both Q1 and Q2 appear to be scr-related enzymes since they are readily recognised by anti-SEEP serum raised against the highly conserved segment at positions 330-345 of p60c-scr. Q1, but not Q2, interacts with a specific antibody raised against the N-terminal segment of p55c-fgr. Microsequence analysis of tryptic fragments generated from Q1 revealed five peptides which exactly overlap the expected segments of p55c-fgr. Two of these peptides were not entirely conserved in any of the other src-related tyrosine protein kinases. A sixth fragment is very similar, albeit not identical, to the C-terminus of p55c fgr. Microsequence analysis of two tryptic fragments from the other TPK-III fraction, Q2, provided the sequences FQILNSSE and LTTQETGYIPSNY, which are identical to two segments of fyn not entirely conserved in any of the other src related tyrosine protein kinases. These results provide evidence that the spleen tyrosine-protein-kinase fraction, conventionally designated TPK-III, is composed of products from two proto-oncogenes, one of which corresponds to fyn, while the other is either identical or very closely related to c-fgr. PMID- 8365415 TI - Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein. AB - Mouse and human cDNA encoding AES (amino-terminal enhancer of split) and ESG (enhancer of split groucho) proteins with strong similarity to Drosophila enhancer of split groucho protein were isolated and sequenced. Mouse AES-1 and AES-2 proteins, probably resulting from alternative splicing, contain 202 and 196 amino acids, respectively, while mouse ESG protein consists of 771 amino acids. The amino acid sequences of mouse and human AES proteins were found to exhibit approximately 50% identity to the amino-terminal region of Drosophila groucho, mouse ESG and human transducin-like enhancer of split (TLE) proteins. Mouse AES transcripts of 1.5 kb and 1.2 kb were abundantly expressed in muscle, heart and brain. Human AES transcripts of 1.6 kb and 1.4 kb were predominantly present in muscle, heart and placenta. Mouse ESG (homolog of human TLE 3) transcripts of 3.3 kb and 4.0 kb were found only in testis, while human TLE 1 transcripts of 4.5 kb was more abundant in muscle and placenta compared to heart, brain, lung, liver, kidney and pancreas. Human AES, TLE 1 and TLE 3 genes were mapped to chromosomes 19, 9 and 15, respectively, using human and Chinese hamster hybrid cell lines. PMID- 8365416 TI - Basic features of class-I alcohol dehydrogenase: variable and constant segments coordinated by inter-class and intra-class variability. Conclusions from characterization of the alligator enzyme. AB - The enzymatic and structural properties of alligator liver alcohol dehydrogenase have been determined. Aliphatic and alicyclic alcohols serve as substrates for this first reptilian form of the enzyme characterized, with Km values decreasing rapidly from methanol to hexanol, as for the human class I enzymes, and a Km of 1.2 mM for ethanol at pH 9.9. The N-terminus of the 374-residue protein chain is acetyl-blocked. The enzyme is related in descending order to class I > III > V > II of the structurally characterized mammalian alcohol dehydrogenases. This observation is compatible with the presence of a I/III ancestral line. Differences of the enzyme classes exceed those of the species, suggesting an early origin of the classes. Within its enzyme class, the reptilian protein is most closely related to the avian form (82% residue identities), and is closer to the human than to the amphibian form (76%, versus 69%, respectively). This establishes class I alcohol dehydrogenase as an enzyme having fairly constant rate of change during much of vertebrate evolution, approximately 10% residue differences/100 million years of separation between pairs compared. Residues interacting with the substrate and coenzyme are largely conserved. In the alligator enzyme, there are only four replacements in the substrate pocket compared with the human class I gamma subunit, and those are not known to have functional roles. These properties account for the kinetic parameters, and suggest distinct metabolic functions for the class I enzyme in vertebrates. Comparisons of the enzymes of the different vertebrate lines reveal that segment patterns are characteristic features of the class I enzymes. Three segments are 'variable', while two are 'constant', and both these types of segment are identical with those of the classes. There is extensive variability in close proximity to the active site of the enzyme and this appears to constitute a fundamental property of class I liver alcohol dehydrogenases in general. PMID- 8365417 TI - Ferredoxin binding site on ferredoxin: NADP+ reductase. Differential chemical modification of free and ferredoxin-bound enzyme. AB - The chloroplast enzyme ferredoxin: NADP+ reductase (FNR) catalyzes the reduction of NADP+ by ferredoxin (Fd). FNR and Fd form a 1:1 complex that is stabilized by electrostatic interactions between acidic residues of Fd and basic residues of FNR. To localize lysine residues at the Fd binding site of FNR, the FNR:Fd complex (both proteins from spinach) was studied by differential chemical modification. In a first set of experiments, free FNR and the FNR:Fd complex were reacted with the N-hydroxysuccinimidyl ester of biotin. Biotinylated peptides and non-biotinylated peptides were separated on monovalent avidin-Sepharose and purified by high-performance liquid chromatography. Two peptides containing Lys18 and Lys153, respectively, were less biotinylated in complexed FNR than in free FNR. In a second set of experiments, free and complexed FNR were treated with 4 N,N-dimethylaminoazobenzene-4'-isothiocyano-2'-sulfonic acid (S-DABITC) to obtain coloured lysine-modified FNR. Protection of Lys153 was again found by modification with S-DABITC. In addition, Lys33 and Lys35 were less labelled in the S-DABITC-modified. Fd-bound enzyme. FNR modified in the presence, but not in the absence, of Fd was still able to bind Fd, indicating that the Fd-protected residues are involved in the formation of the Fd:FNR complex. The lysine residues disclosed by differential modification surround the positive end of the molecular dipole moment (558 Debye approximately 1.85 x 10(-27) Cm) and are located in a domain of strong positive potential on the surface of the FNR molecule. This domain we had proposed to belong to the binding site of FNR for Fd [De Pascalis, A. R., Jelesarov, I., Ackermann, F., Koppenol, W. H., Hirasawa, M., Knaff, D. B. & Bosshard, H. R. (1993) Protein Science 2. 1126-1135]. The prediction was based on the complementarity of shape between positive and negative potential domains of FNR and Fd, respectively. PMID- 8365418 TI - An arrestin homolog of blowfly photoreceptors stimulates visual-pigment phosphorylation by activating a membrane-associated protein kinase. AB - An arrestin homolog (Arr2, 49-kDa protein) of blowfly (Calliphora erythrocephala) retinae undergoes light-dependent reversible binding to the photoreceptor membrane. In order to characterize this arrestin homolog and to study its function in a well-defined experimental system, we developed a purification scheme which used microvillar photoreceptor membranes as an affinity binding matrix. Additional purification steps included ammonium sulfate precipitation, gel filtration and binding to heparin-agarose. The molecular mass of purified Arr2, as judged by SDS/PAGE, is in the range 45-49 kDa. The isoelectric point, as judged by gel isoelectric focussing, is 8.7. Arr2 is specific to the retina, where it is subject to phosphorylation at multiple sites. Binding of purified Arr2 to isolated photoreceptor membranes efficiently activates the light-induced phosphorylation of visual pigment. Since the assay system used is deficient in rhodopsin phosphatase activity, the arrestin-stimulated phosphate incorporation into rhodopsin results solely from the activation of a protein kinase. Phosphorylation experiments with highly purified membrane preparations indicate that rhodopsin kinase is tightly associated with the rhabdomeric membrane or the microvillar cytoskeleton. Rhodopsin kinase is released from the membrane or inactivated upon treatment with urea. It is concluded that this arrestin is a regulator protein that controls visual-pigment phosphorylation by affecting the interaction of metarhodopsin and rhodopsin (metarhodopsin) kinase. PMID- 8365419 TI - Non-cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei. AB - The life cycle of Trypanosoma brucei brucei involves a series of differentiation steps characterized by marked changes in mitochondrial development and function. The bloodstream forms of this parasite completely lack cytochromes and have not been considered to have any Krebs cycle function. It has been suggested that glycolysis is the sole source of ATP in all bloodstream forms. However, earlier results indicated that in the mitochondria of the transitional intermediate/short stumpy bloodstream forms, the biochemical pathways are present that could allow intra-mitochondrial production of ATP. Using a high mannitol buffer to enhance permeability, we confirm previous observations showing that transitional forms maintain motility and respiratory activity with 2-oxoglutarate as the sole substrate. Using a luminometer to measure intracellular ATP levels via the luciferin/luciferase chemiluminescence assay, we show that these same transitional forms, but not long slender forms, maintain high levels of intracellular ATP in the presence of 2-oxoglutarate. Further, in the presence of bongkrekic acid, an inhibitor of the mitochondrial adenine nucleotide translocase, ATP levels are reduced with subsequent death and lysis of the cells when 2-oxoglutarate, but not glucose, is used as sole substrate. These data are direct evidence of ATP production by transitional bloodstream form mitochondria. PMID- 8365420 TI - The proteolytic susceptibility of specific sites in myosin light chains is modulated by the filament conformation. AB - The proteolytic susceptibilities of specific sites in the LC1 and LC2 N-termini were modulated by ionic strength in myosin (a species able to form filaments) but not in S1. (a) In the presence of Ca2+ or Mg2+, the proteolytic susceptibility (apparent initial reaction rate) showed a sharp discontinuity at a critical ionic concentration similar for LC1', LC2' and LC2'' cleavages. (b) The susceptibility of LC1' and LC2'' was higher at low ionic concentration in the more compact structure of the filament than in the dissociated form at high ionic concentration. (c) The ionic concentration effect was no longer observed with species unable to form filaments. (d) This effect occurred at a critical ionic concentration markedly different from the critical concentration at which the monomer-filament equilibrium was found. These observations lead to the following conclusions. (a) The ionic concentration effect is an attribute of the filament structure. (b) In the filament the faster cleavage at sites (LC1' and LC2'') near the LC1 and LC2 N-termini are due to an extended configuration of the N-terminal segment binding to a site in the filament structure. (c) The slower rate of formation of LC2' in the filament indicates that the N-terminal segment of LC2 binds more tightly to the structure than that of LC1. (d) The critical ionic concentration is not that of the filament-monomer equilibrium but corresponds to the order-disorder transition of the heads in the filament. These results suggest that the N-termini of the light chains (here in striated muscles) play a role in a secondary regulatory mechanism. The analysis of these regions may contribute to our understanding of the altered activity and regulation seen in such diseases as idiopathic dilated cardiomyopathy [Margossian, S. S., White, H. D., Caulfield, J. B., Norton, P., Taylor, S. & Slayter, H. S. (1992) Circulation 85, 1720-1733]. PMID- 8365421 TI - Elastic behaviour of the carotid artery in intact spontaneously hypertensive rats. AB - Intact spontaneously hypertensive rats (SHR) were studied to assess the effect of prolonged antihypertensive treatment on the elastic behaviour of the external carotid artery. Thirty-week-old SHR received the ACE inhibitor captopril, the arteriolar dilator hydralazine or their vehicle for 6 weeks. These rats were compared to normotensive, vehicle treated WKY rats. The internal diameter of the carotid artery was measured continuously in halothane-anaesthetized rats using an echo-tracking device, and intra-arterial pressure was also monitored continuously, on the contralateral side. Captopril- and hydralazine-treated SHR as well as normotensive controls had similar blood pressure values. No significant shift in the distensibility-pressure curves was observed among vehicle-treated SHR and WKY rats or the SHR which had received captopril or hydralazine. Histological examination of the carotid artery fixed ex vivo with paraformaldehyde showed a significant increase in cross-sectional area in vehicle treated SHR as compared to their normotensive counterparts. These results therefore suggest that the elastic behaviour of elastic arteries is not necessarily altered by the structural changes developing in response to hypertension. PMID- 8365422 TI - Heart failure, ventricular remodelling and the renin-angiotensin system: insights from recently completed clinical trials. AB - Increased insight has been gained into the pathophysiology of heart failure, which is now recognized as a milieu created by specific diseases that cause myocardial dysfunction resulting in haemodynamic abnormalities. Subsequent compensatory circulatory and hormonal changes cause substantive metabolic derangement, and it is the haemodynamic and metabolic abnormalities that produce the congestive and low cardiac output symptoms and physical findings associated with heart failure. One of the earliest abnormalities noted in the failing heart is activation of the renin-angiotensin-neurohormonal axis. This is associated with both dilation and hypertrophy of the left ventricle. This remodelling may be regulated, at least in part, by myocardial tissue angiotensin-converting enzyme systems. Clinical drug trials in patients with heart failure have demonstrated that certain agents reduce mortality and interdict detrimental hormonal activity and remodelling. The Veterans Administration's (VHEFT-I and II) and Scandinavian (CONSENSUS-I) heart failure trials, as well as Studies of Left Ventricular Dysfunction (SOLVD) and the post myocardial infarction captopril trial (SAVE- Survival and Ventricular Enlargement) indicate that vasodilators and, in particular, angiotensin-converting enzyme inhibitors, decrease heart failure mortality. Furthermore, diminution in morbidity measured as a reduction in hospitalization for congestive heart failure or myocardial infarction was a dramatic beneficial effect noted even in relatively asymptomatic patients with left ventricular dysfunction. Importantly, in the SOLVD and SAVE trials, the diminution in major ischaemic events observed in the treatment groups were noted whether drug was started one week (SAVE) or one year (SOLVD) post infarct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365424 TI - Vascular remodelling in hypertension. AB - Essential hypertension is associated with alterations in the structure of the resistance vasculature, such that the ratio of the media thickness to the lumen diameter (media:lumen ratio) is increased. These abnormalities have previously been explained in terms of vascular growth (an encroachment of the wall into the lumen), but the abnormalities could also be due to a rearrangement of a normal amount of material around a smaller lumen, a process known as 'remodelling'. This paper reviews briefly some of the evidence for vascular remodelling as an important factor in the pathogenesis of essential hypertension. PMID- 8365423 TI - Influence of angiotensin converting enzyme inhibition on exercise performance and clinical symptoms in chronic heart failure: a multicentre, double-blind, placebo controlled trial. AB - One hundred and seven patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diuretics, recruited from 11 centres were randomized into a double-blind, placebo-controlled study to assess the effect of 12 weeks of cilazapril therapy on exercise tolerance and clinical status. Thirty five patients were randomized to placebo and 72 to cilazapril at a starting dose of 1 mg daily; titration to cilazapril 2.5 mg at week 4 and 5 mg at week 8 (or matching placebo) was carried out in patients who did not improve clinically. Demographic characteristics, including exercise test duration increased from 402 s (+/- 17 SEM) at baseline to 462 s (+/- 19 SEM) at week 12 for the cilazapril group (+15%) and from 405 s (+/- 23 SEM) at baseline to 408 s (+/- 30 SEM) at week 12 in patients on placebo (+1%) (P < 0.001). In the placebo group, patients able to exercise for more than 6 min at baseline showed an increase in exercise duration at week 12 while those able to exercise for up to 6 min at baseline showed a decrease (P = ns). In contrast, cilazapril-treated patients showed an increase in exercise tolerance regardless of baseline exercise test duration; patients with the most impaired exercise tolerance at baseline showed a greater improvement than patients with mildly impaired baseline exercise tolerance (P < 0.05 vs placebo). NYHA class improved by at least one grade in 51% of the cilazapril group vs 32% in the placebo group (P = ns). At the end of the trial, 15% of the patients were non-responders on cilazapril vs 41% on placebo (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365425 TI - Ventricular remodelling: consequences and therapy. AB - The mammalian left ventricle can change its size and shape in response to a variety of stimuli including loss of tissue and external work. These changes in size and shape, defined as remodelling, are the sum total of a number of processes that involve the myocyte and the interstitial fibrous structures which provide the matrix in which the myocyte functions. The adapted mechanisms which occur are affected by humoral and cellular phenomena and can be modified by pharmacological agents. This paper reviews the remodelling process that occurs in myocardial infarction and heart failure and the effect of various pharmacological agents on this remodelling process. PMID- 8365426 TI - Effects of angiotensin converting enzyme inhibition on endothelial vasodilator function in primary human hypertension. AB - Hypertension in animal models and in humans is associated with a decreased vasodilator response to acetylcholine which causes vascular relaxation by release of endothelium-derived relaxing factor from the endothelium. Since lowering of blood pressure, particularly with angiotensin converting enzyme inhibitors, improved the response to acetylcholine we investigated the effects of brachial artery infusions of ascending dosages of acetylcholine on forearm blood flow before and after 5 months of therapy with the angiotensin converting enzyme inhibitor, cilazapril, in 10 patients with mild to moderate primary hypertension. Cilazapril decreased blood pressure from 150.8 +/- 14.4/98.9 +/- 4.3 mmHg during placebo to 138.8 +/- 15.6/88.6 +/- 8.9 mmHg (P < 0.01). Brachial artery acetylcholine infusions increased forearm blood flow from 2.95 +/- 1.5 to a maximum of 22.8 +/- 11.5 ml.min-1.100 ml-1 forearm tissue and decreased forearm vascular resistance from 48.1 +/- 34.1 to 6.9 +/- 6.9 units before cilazapril. This response did not change after cilazapril therapy. Our findings in patients with primary hypertension, therefore, do not support the concept that angiotensin converting enzyme inhibition influences endothelium-dependent vascular relaxation to acetylcholine to a significant degree. Whether this lack of effect on endothelial vasodilator function is specific for the vascular bed chosen for study or whether it represents a fundamental difference between animal models and human hypertension remains an important issue to be clarified. PMID- 8365427 TI - Outcome of patients with untreated cancer of the prostate. AB - A group of 74 patients among 1,663 patients with biopsy-proven prostate cancer of various stages who, contrary to the usual practice, received no treatment were followed at the outpatient clinic of the Inselspital university hospital in Berne, Switzerland. The aim of this study was the evaluation of the number of patients eventually succumbing to cancer of the prostate, the survival figures for these patients, and the prognostic value of minimal clinical staging. Thirteen patients had hormonal treatment at a later stage, but 61 of 1,663 patients (3.7%) were never treated for prostate cancer. Overall survival for all 61 patients was 50% at 5 years and 24% at 10 years. Overall disease-specific survival was 75% at 10 years. In the group with organ-confined disease (T0-2) actuarial 5- and 10-year survival rates were 67 and 34%, respectively, whereas in the group with extraprostatic disease (T3-4) the respective survival rates were 11 and 0%. Disease-specific 5- and 10-year actuarial survival was 89% in the T0-2 group and 51 and 0% in the T3-4 group. The cause of death in 30 patients was reported as disease-related in 8 patients (26.6%), unrelated to prostate cancer in 18 patients (60%) and unknown in 4 patients (13.3%). Despite the absence of treatment for a mostly clinically overt prostate cancer the majority of patients apparently did well and eventually died from other causes. PMID- 8365428 TI - Pedicled gastric tube as a catheterising conduit. AB - Treatment of urinary and faecal incontinence using the Mitrofanoff principle or the antegrade continence enema technique requires the creation of a catheterisable stoma. Although the appendix is by far the most satisfactory structure for the creation of this channel, its removal or use in previous surgical reconstruction may force the use of alternatives. We describe the use of the pedicled gastric tube for this purpose. PMID- 8365429 TI - Experience with one-stage repair of severe proximal hypospadias: operative technique and results. AB - Our experience with one-stage repair of severe proximal hypospadias in children is reported. The operative technique, which makes one-stage repair of hypospadias and associated bifid scrotum feasible, is described in detail. A 45% chance of secondary repair notwithstanding, we recommend our one-stage repair for all children with severe hypospadias. PMID- 8365430 TI - Endoscopic correction of vesico-ureteric reflux in duplex systems. AB - Between May 1984 and April 1990, 37 children with vesico-ureteric reflux (VUR) in 43 duplex systems were treated by endoscopic subureteric Teflon injection (STING). There were 32 girls and 5 boys; the duplex systems were complete in 27 refluxing units and incomplete in 16 refluxing units. All patients had high-grade reflux. In incomplete duplicated systems, VUR was corrected in 14 (87.5%) after a single injection of polytef paste and 2 patients required 2 injections to correct VUR. Of the 27 refluxing units with complete ureteral duplication, reflux was corrected in 16 (59%) units after a single injection of polytef paste, and 3 (11%) units showed improvement of VUR to grade I or II after 1 injection; no further treatment was given. 7 units with complete ureteral duplication required 2-4 injections for correction of VUR. STING failed to correct VUR in 1 duplex system which required a re-implantation. In 93% of refluxing units where VUR was corrected by a single injection, the quantity of polytef paste used was less than 0.3 ml. 36 (97%) of patients were discharged home on the day of the procedure. All patients were followed up for 2-8 years. Of the corrected ureters, there were no recurrences in the incomplete duplicated ureters. 3 of the completely duplicated ureters showed recurrence of reflux at follow-up micturating cystography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365431 TI - Laparoscopic nephrectomy with vaginal delivery of the intact kidney. AB - The first case of laparoscopic nephrectomy in Italy is described. The patient was a 51-year-old woman with a small, nonfunctional, tuberculous left kidney. The organ, once detached from its lumbar site, was brought in to the pelvic cavity and extracted from the body via a posterior colpotomy. In this way, the integrity of the organ is preserved, hence, this could be the preferable route when dealing with a little kidney tumor in a woman. PMID- 8365432 TI - A modified Winter's procedure for priapism treatment with a new trocar. AB - A modified Winter's procedure with trocar which was used for 7 patients with priapism is presented. Complete detumescence was resumed in 5 of 7 patients. Cavernosaphenous shunt was used for only 2 patients. Two patients had postoperative impotence. PMID- 8365433 TI - Pathologic parameters and flow cytometric ploidy analysis in predicting recurrence in carcinoma of the prostate. AB - Recurrence of prostate cancer following radical prostatectomy is determined by the extent of local disease. Tumor volume and grade have improved our ability to predict extraprostatic extension, but tumors of intermediate volume and grade vary in their biologic behavior. To assess the prognostic significance of DNA ploidy, we performed flow cytometry in 85 patients with prostate cancer volumes > 4 cm3. Post-radical prostatectomy serum prostate-specific antigen was used to prove recurrence of cancer. Mean follow-up was 35 months (median 31 months). 26 patients (30%) had diploid histograms, 55 (65%) non-diploid histograms. In 4 cases (5%) the histograms were uninterpretable. Tumor volume and percent of Gleason grades 4 or 5 separated the recurrent from nonrecurrent groups in a highly significant manner (p < 0.001). When tested alone, ploidy had no ability to predict recurrence (p = 0.26). However, in a subset of patients with 4-8 cm3 of cancer with < 30% Gleason grade 4 or 5 tumor, ploidy conferred significant additional prognostic information (p < 0.005). PMID- 8365434 TI - Reappraisal of the biological role of epidermal growth factor receptor in transitional cell carcinoma. AB - Retrospective immunohistochemical and flow cytometric DNA analyses were performed on 56 cases of transitional cell carcinoma (TCC) to examine the biologic implications of epidermal growth factor receptor (EGFR) expression. A total of 28 (50%) cases were reactive for EGFR immunostaining. The receptor expression increased from 41.7 to 56.3% with tumor stage. There was a significant association between EGFR expression and tumor stage (p < 0.0005), but not tumor grade. The flow DNA content and the Ki-67 proliferating index had no relation to the status of EGFR (p = 1, respectively). For those receptor-positive tumors (n = 28), there was a significant association (p < 0.0001) between receptor expression and tumor proliferation. Interestingly, the DNA content was not correlated with EGFR expression (p = 0.69). We support the possible role of EGFR in cell proliferation and the potential significance for tumor growth in TCCs. However, the biology of TCC in half the cases could not be explained by this mechanism. The interaction between EGFR and DNA ploidy status necessitates further evaluation. PMID- 8365435 TI - Early diagnosis of prostatic carcinoma may be achieved through in vitro culture of tumor cells harvested by prostatic massage. AB - As a new method for early diagnosis of prostatic carcinoma we succeeded in growing in vitro the epithelial cells which can be collected from prostatic fluid after rectal prostatic massage. We report here the updated and statistically analyzed series of data (174 patients) on this new approach, which allows all the harvested cells to express their biological features. The method reaches a sensitivity of 72-86% and a specificity of 88-100%. This noninvasive test, which is also suitable for mass screening, may be very useful for an early diagnosis of the neoplasm. PMID- 8365436 TI - Pharmacocavernometry with prostaglandin E1. AB - The aim of this study was to define the normal response of cavernometry parameters with high-dose pharmacostimulation, to investigate repeatability of the method and to find out the incidence of cavernovenous leakage in impotence. 82 consecutive impotent patients and 10 potent control subjects underwent pharmacocavernometry with 40 micrograms of prostaglandin E1. In control subjects, the maintenance flow at 150 mm Hg (MF150) was 3-22 ml/min with an average of 6 ml/min (SD = 6 ml/min). Cavernometry was repeated in 17 patients, but the repeatability of quantitative parameters was disappointing. Cavernovenous leakage was estimated to be present in 55-67% of all impotent patients. Cavernometry with a high-dose prostaglandin E1 pharmacostimulation is a useful method in selected patients, but the consistency of the method should be improved. PMID- 8365437 TI - Duplex Doppler scanning with high-dose prostaglandin E1 stimulation in the diagnosis of arteriogenic impotence. AB - The aim of this study was to find out the normal range of penile duplex Doppler parameters with pharmacostimulation of 40 micrograms prostaglandin E1 and to assess the repeatability and clinical value of the method. Maximal systolic velocity increase (SVImax) is presented as a new flow parameter. 10 potent and 82 impotent patients were investigated. Peak systolic velocity values were significantly higher when recorded at proximal than at distal penis. Repeatability of SVImax was fairly good (coefficient of variation = 0.18). SVImax ranged from 32 to 100 cm/s in 10 control subjects. The distribution of SVImax values in patients grouped according to the number of arteriosclerotic risk factors indicates that this parameter may be useful in the diagnosis of arteriogenic impotence. PMID- 8365438 TI - Is the volume injected a parameter likely to influence the erectile response observed after intracavernous administration of an alpha-blocking agent? AB - In 12 impotent patients with spinal cord injury, we assessed the erectile response induced by intracavernous administration of 20 mg moxisylyte dissolved in 4 different volumes of solvent. We tested successively in each patient 0.4, 0.8, 1.2 ml and the volume usually injected of 2 ml, with a 7-day interval between 2 injections. The reduction in the volume from 2 to 0.4 ml did not thwart the quality of erection obtained by the intracorporeal administration of 20 mg moxisylyte. Indeed, for each erectile parameter (rigidity, abdominopenile angle, length and circumference of the penis), no statistically significant difference arose between the 4 tests. All patients achieved full rigidity. Neither priapism nor prolonged erection occurred. These results suggest that discreet and easily handled small-sized injection pens, containing little solution, could be conceived for autoinjection therapy. PMID- 8365439 TI - Predicting the outcome of radical radiotherapy for invasive bladder cancer. AB - The correlation between T stage, histological grade, the presence of squamous metaplasia, and nuclear morphometry scores and response to radiotherapy and survival was investigated in 60 patients with muscle invasive transitional cell carcinomas of the bladder. Patients with T2 tumours showed a complete response significantly more often than those with T3 lesions. Multivariate analysis showed that T stage and initial response to radiotherapy were very strong predictors of survival though they were not independent variables. Histological grade, the presence of squamous metaplasia, and nuclear morphometry scores were not found to have any predictive value. PMID- 8365441 TI - Pre- and post-nephrectomy kidney enlargement in patients with contralateral renal cancer. AB - Pre- and post-nephrectomy kidney growth was studied by computed tomography (CT) in 32 patients with contralateral renal cancer. Kidney enlargement was assessed by comparing the size of the unaffected kidney, in 32 pre- and 61 post nephrectomy CT examinations, with the corresponding normal size, determined from 120 CT examinations of binephric individuals with no renal disease. The unaffected kidney was found to be 36% larger 1 month before nephrectomy and 54, 62 and 47% in the 1st, 2nd, and 3rd postoperative year, respectively. Compensatory renal growth was influenced both by contralateral cancer and nephrectomy and did not depend on the patient's age or sex. PMID- 8365440 TI - Neutron therapy of bladder carcinoma: can a high rate of severe complications be avoided in neutron therapy? AB - We reviewed retrospectively a series of 58 patients with deeply invasive bladder cancer treated with fast neutron therapy (p(65) + Be) in order to evaluate its tolerance and side effects. Patients were divided into three groups according to treatment technique. Patients of group A received whole pelvis irradiation up to 50 Gy photon equivalent followed by a boost to the bladder up to 57-66 Gy photon equivalent (40-56 days). Group B patients were treated by a split course regimen of 30 Gy photon equivalent on the whole pelvis at 3-4 weeks interval (66-108 days). Group C patients, not suitable for radical treatment, received only 40-54 Gy photon equivalent (26-70 days). The overall 5-year actuarial survival rate was 30% (SE 8%). As expected, T stage was a statistically significant prognostic factor. The overall local control rate reached 21% at 4 years. Acute and late side effects were minimal to moderate. These results suggest that high-energy neutron beam treatment is at least as effective as photon beam treatment for bladder carcinoma, without a higher incidence of major side effects. PMID- 8365442 TI - One-shot intravesical instillation of the mucous adhesive anticancer agent hydroxypropylcellulose-doxorubicin for the treatment of superficial bladder carcinoma is sufficient to determine antitumor effects. AB - A 20 mg/20 ml dose of the membrane adhesive anticancer preparation, hydroxypropylcellulose-doxorubicin (HPC-doxorubicin), was instilled into urinary bladders through a catheter for the treatment of superficial bladder carcinomas (Ta-T1). After 14-30 days, the effects of the drug on tumors was examined by cystoscopy, and the residual tumor tissue where reduction in size was observed was resected by transurethral resection (TUR). Therapeutic effects were as follows: a complete response (CR) was found in 6 cases (37.5%), a reduction in size of more than 50% (partial response = PR) in 4 cases (25%), and a less than 25% reduction (no change = NC) in 6 cases (37.5%). In no case was progression of the disease noted. In CR cases, cold cup punch biopsy revealed no tumor cells remaining at the site where the tumor was present before the instillation. Side effects such as bladder irritation were found in 4 cases, but they were only temporary in nature. The one-dose HPC-doxorubicin approach developed by ourselves allowed detection of antitumor effects between 14 and 30 days after the instillation and therefore determination of sensitivities at an earlier stage than with instillation of the conventional water-soluble type of doxorubicin hydrochloride. PMID- 8365443 TI - Correlation between ultrasonic appearance and histology of periprostatic tissue. AB - We compared preoperative echograms and postoperative histological specimens from 16 patients who had undergone radical prostatectomy or radical cystourethrectomy to evaluate the correlation between the so-called capsular echogram obtained on transrectal ultrasonography and histology of the prostatic capsule. The capsular echogram corresponded to the periprostatic fatty tissue in all cases. In 10 of the 16 cases lateral ruptures of the capsular echogram were observed. Histologically, these ruptures corresponded to fibrous bundles in 6 of the 10 cases and to neurovascular bundles located close to the prostatic tissue in the other 4 cases. Because the prostatic glands, prostatic capsule, blood vessels and nerve fibers complicated the structure on the lateral sides near the apex, the borders of the prostatic gland were indistinct on the echograms. PMID- 8365444 TI - Quality of life after radical retropubic prostatectomy for carcinoma of the prostate. AB - 131 patients treated by radical prostatectomy for localized prostatic cancer were studied with regard to quality of life. The patient's perception of his state of health before operation and 3, 6, 12 and 18 months later was assessed by questionnaires on 272 occasions. In the short term the patients complained of anxiety, voiding disorders, and loss of potency. In the long term only distress due to lack of erection persisted, but the overall well-being after 18 months was nevertheless better than before treatment. PMID- 8365445 TI - Urethroplasty for severe urethral strictures, using the preputial island flap technique: revisited. AB - We reviewed our experience with the pedicled island flap technique in severe urethral strictures, especially in regard of the long-term follow-up of functional parameters: micturition patterns and sexual behavior. Analysis of 59 consecutive cases treated with this approach has proven the value of this technique. The results of a questionnaire and the current clinical status showed that, of the 59 cases, 12 patients were subjectively dissatisfied with their micturition, independent of the results of functional voiding measurements, and 2 patients complained of impaired potency: 1 immediately after the original trauma, the other after the surgical repair. The most frequent reported micturition complaints were only minor: dribbling, nycturia and frequency, mostly already existing before the operation. The objective results, obtained postoperatively by uroflowmetry were good, but often did not correlate with the subjective results. The overall results are satisfactory. Only 3 patients replied to say that they regret having had the open operative procedure. PMID- 8365446 TI - Laser treatment of glans penis hemangioma. AB - We present a case of a glans penis hemangioma. These lesions are extremely rare, and as a consequence there is controversy concerning their treatment and outcome. Our patient was treated with a neodymium:YAG laser irradiation, with complete morphological recuperation. To our knowledge this is the first case of a glans penis hemangioma treated with this technique. PMID- 8365448 TI - Is the sensory innervation disturbed in the lower urinary tract of children with bed-wetting? AB - The sensation of bladder filling during cystometry and the sensory thresholds towards electrical stimulation in the bladder and urethra were determined in a group of 35 children and young adults with enuresis nocturna and in 28 similar patients with other urodynamic dysfunctions. The variables of the filling sensation were not different between the groups. The sensory threshold of the urethra in girls was significantly higher in the bed-wetting group indicating a diminished electrosensation in this structure. In 2 patients with absent electrosensation, an unsuspected neuropathy was discovered. A search for an eventual deficient sensation in the lower urinary tract in children with persistent enuresis nocturna would seem worthwhile. PMID- 8365447 TI - Endopyelotomy for pelvi-ureteric junction obstruction in children. AB - Endopyelotomy or percutaneous pyeloplasty has become an attractive alternative to open pyeloplasty in adult patients in recent years. However, the experience and reports of this procedure in the paediatric population have been limited to date. We report our experience in paediatric patients undergoing this procedure. Seventeen children with primary (14) or secondary (3) pelvi-ureteric junction (PUJ) obstruction were consented for endopyelotomy over a 3-year period. Patient age ranged from 4 months to 16 years, and the male to female ratio was 11:6. Percutaneous nephrostomy was established in 5 patients prior to endopyelotomy either for diagnosis or for drainage of an acutely obstructed upper tract. The remaining 12 had endopyelotomy as a one-stage procedure. The average duration of the procedure was 103 min (range 60-150 min) and the average hospital stay was 5 days (range 3-9 days). Follow-up averaged 15 months (range 3-36 months). Endopyelotomy was successful in 10/13 patients (77%), unchanged in 1, and failed in the remaining 2. We believe that percutaneous pyeloplasty can be safely and successfully performed in children with primary and secondary PUJ obstruction. PMID- 8365449 TI - Comparison of urodynamic findings and response to oxybutynin in nocturnal enuresis. AB - Sixty-three children with persistent nocturnal enuresis were urodynamically assessed and subsequently treated with oxybutynin chloride. Urodynamic evaluation, including graduation of detrusor instability and comparison of maximum bladder capacity with the age-predicted norm, confirmed an inadequate storage function in 84% of the children. Treatment benefit totaling 70% was dependent upon urodynamic findings, with best relation to the determined bladder capacity. The value attributed to graduation of uninhibited contractions was prognostic in accordance with further subdivision of the maximum bladder capacity. Treatment benefit was limited in children with normal urodynamic findings. PMID- 8365450 TI - Sleep polygraphic studies using cystomanometry in twenty patients with enuresis. AB - Polygraphic exploration during sleep using cystomanometry was performed in 20 patients aged 7-17 years with primary (17) or secondary (3) enuresis. In this group of patients, 9 presented with isolated nocturnal enuresis while 11 patients had associated diurnal micturition troubles. During this study we documented 24 episodes of enuresis. There was no disturbance in sleep architecture or correlation between the uncontrolled micturition and any particular state or stage of sleep. Most episodes of enuresis occurred in a unique pattern in which a sudden or progressive intravesical increased pressure was associated with an awakening reaction. From a physiopathologic point of view, our findings are in favor of immaturity of the central system of inhibition of micturition reflex during sleep. PMID- 8365451 TI - Antihypertensive effect of chronic i.v. administration of 5-carboxamidotryptamine in spontaneously hypertensive rats. AB - The effects of chronic i.v. administration of the serotonin 5-HT1 receptor agonist, 5-carboxamidotryptamine (5-CT), on blood pressure (BP), heart rate (HR) and baroreflex sensitivity were studied in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acute i.v. injection of increasing doses of 5-CT resulted in a dose-dependent reduction in mean arterial pressure (MAP) in SHR and WKY with concomitant tachycardia. In chronic experiments, 5-CT (15.0 micrograms/kg per day) or vehicle (24.0 microliters/day) was infused i.v. for 7 days, using osmotic minipumps. Systolic blood pressure (SBP) and HR were monitored daily before and during infusions. In SHR (n = 8) and WKY rats (n = 9) receiving 5-CT, a significant reduction in SBP was observed during the infusion period. HR was slightly increased in WKY rats on days 1 and 2. There were no HR changes in the SHR group. The fall in SBP was significantly larger in the SHR than in the WKY rats. Baroreflex sensitivity on day 7 was significantly greater in 5-CT-treated SHR than in control rats. There was no change in baroreflex sensitivity in WKY rats. Administration of a single dose of 5-CT (0.5 microgram/kg i.v.) on day 7 of infusion resulted in attenuated responses in WKY rats while SHR responded as their respective controls. Our data suggest that chronic administration of 5-CT results in a sustained antihypertensive effect. This is associated with an improved BRS in the SHR either as a consequence of a resetting of the baroreflex due to sustained lowering of BP or a direct action of 5-CT on baroreflex sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365452 TI - Alteration of eicosanoid production in the sensitized guinea pig lung by CS-518. AB - The effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo [b]thiophene-6-carboxylate), a thromboxane A2 synthase inhibitor, on changes in arachidonic acid metabolism were investigated in the lung of actively sensitized guinea pigs. Antigen challenge enhanced the production of thromboxane A2 as well as histamine and peptide leukotrienes in lung fragments. Exogenous leukotriene D4 also stimulated significant thromboxane A2 production in the non-sensitized lung in vitro. CS-518 was effective in preventing the thromboxane A2 production induced by either antigen or leukotriene D4, and the IC50 values were 90 and 7.5 ng/ml (320 and 27 nM), respectively. CS-518 markedly potentiated the production of prostaglandin E2 and I2 with slight inhibition of leukotriene formation, but indomethacin significantly stimulated leukotriene production. When CS-518 was administered orally, it induced long-lasting inhibition of thromboxane A2 production and potentiation of prostaglandin I2 production in guinea pig lung. Thus, CS-518 not only inhibited thromboxane production but also improved the change in arachidonic acid metabolism in the guinea pig bronchoalveolar tissue during allergic reaction in vivo as well as in vitro, which suggests amelioration of the asthmatic condition. PMID- 8365453 TI - Protective effect of fructose 1,6-bisphosphate against carrageenan-induced inflammation. AB - Administration of carrageenan (0.5 mg) to the plantar tissue of rats resulted in reversible inflammatory injury. This damage was monitored as changes in foot volume, using a plethysmometer. Administration of fructose 1,6-bisphosphate at different doses, orally or intraperitoneally, prevented the inflammatory action induced by the simultaneous injection of carrageenan in the rat paw. The effect was dose and time dependent. In contrast, fructose or fructose 6-phosphate afforded no significant protection. In order to extend the average half-life of the drug, we prepared liposomes of fructose 1,6-bisphosphate which, administered orally or intraperitoneally, showed a greater and more prolonged antiinflammatory action. The significance of these findings with respect to the mechanism of the antiinflammatory action of fructose 1,6-bisphosphate is discussed. PMID- 8365454 TI - Effects of treatment with myo-inositol or its 1,2,6-trisphosphate (PP56) on nerve conduction in streptozotocin-diabetes. AB - Nerve conduction abnormalities in peripheral nerves from diabetic patients may be early indicators for the future development of symptomatic neuropathy. In this study, three weeks of experimental diabetes in the rat caused a significant decrease in motor nerve conduction velocity measured in vivo (45.3 +/- 3.6 m/s; mean +/- S.D.) compared to controls (57.7 +/- 4.5 m/s). myo-Inositol administration to diabetic rats (500 mg/rat per day) for the duration of the study, partially prevented this decrease (50 +/- 4.4 m/s). An analogue of myo inositol, PP56 (D-myo-inositol-1,2,6-trisphosphate), at a dose of 24 mg/rat per day completely prevented this reduction in diabetic rats (53.4 +/- 5.8 m/s). Resistance to hypoxic conduction block was determined in vitro in endoneurial preparations and was assessed as the decline in compound action potential amplitude over a 40 min period of hypoxia. Compound action potential amplitude (as % of initial value +/- S.D.) was significantly greater in diabetic preparations compared with controls at 40 min of hypoxia (76.1 +/- 9.1 vs. 54.8 +/- 14.7 respectively). Treatment to diabetic rats with myo-inositol did not significantly affect this value (79.9 +/- 16.6) but PP56 treatment partially prevented the increased resistance to hypoxic conduction block (69.4 +/- 16.0). This study demonstrates that these acute abnormalities of nerve function in early experimental diabetes may be attenuated by the administration of PP56, possibly acting via a vascular mechanism. PMID- 8365455 TI - Endothelin-1 induces vasoconstriction and prostacyclin release via the activation of endothelin ETA receptors in the perfused rabbit kidney. AB - Endothelin-1 (0.005 and 0.01 nmol) induced a dose-dependent increase in perfusion pressure in the perfused rabbit kidney. These pressor effects were markedly reduced by an endothelin ETA receptor antagonist, BQ-123 (0.1 microM). Similarly, the release of prostacyclin triggered by intra-arterial infusion of endothelin-1 (10 nM) was significantly reduced in a concentration-dependent manner when the kidney was pretreated with BQ-123 (0.5-1 microM). In contrast, two selective ETB receptor agonists, BQ-3020 and IRL 1620, were found to be inactive, both as pressor agents and releasers of prostacyclin at doses (for the pressor effects) and concentrations (for the prostacyclin generation) 50-100 times higher than those of endothelin-1. BQ-123 (1 microM) did not modify the pressor or prostanoid releasing properties of angiotensin II. These results confirm our previous observations suggesting that pressor responses and prostanoid release induced by endothelin-1 are mediated via the selective activation of ETA receptors in the perfused rabbit kidney. PMID- 8365457 TI - Effects of dipyridamole in spontaneously hypertensive rabbits with diffuse chronic cerebral ischemia. AB - The effect of intravenous dipyridamole (0.7 mg/kg) on cerebral blood flow (CBF), mean arterial blood pressure (MABP), heart rate, respiration rate, cerebral electrical activity, arterial blood gases, pH, and glucose was investigated in 14 normotensive and 14 stroke-prone spontaneously hypertensive anesthetized rabbits. CBF was measured by hydrogen and heat clearance. In both groups, MABP decreased (normotensive: -24 mm Hg, hypertensive: -47 mm Hg; ANOVA: P < 0.0001) and CBF increased (normotensive: +59 ml/100 g/min, hypertensive: +72 ml/100 g/min; ANOVA: P < 0.0002). CBF returned to the initial level 21 min later in hypertensive than in normotensive rabbits. Changes in other parameters were insignificant. In additional experiments, 30 mg/kg theophylline entirely prevented the cerebral vasodilator and systemic hypotensive effects of dipyridamole in both normotensive and hypertensive rabbits. We conclude that, in stroke-prone spontaneously hypertensive rabbits, the longer-lasting and larger CBF increase in response to dipyridamole may be attributed to reversible functional changes in the cerebral vasculature resulting from hypertension. PMID- 8365456 TI - WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. AB - The novel phenylpiperazine derivative, (+/-)-WAY100135 (N-tert-butyl-3-(4-(2 methoxyphenyl)piperazin-1-yl)-2-phenylpro pionamide dihydrochloride), is a selective antagonist at both somatodendritic and postsynaptic 5-HT1A receptors. The IC50 of (+/-)-WAY100135 at the rat hippocampal 5-HT1A receptor was 34 nM, whereas its IC50 at a range of other receptor sites was > 2 microM. Up to a dose of 2.5 mg/kg i.v. (+/-)-WAY100135 induced a maximum 30% inhibition of raphe neuronal firing and (at 0.5 mg/kg i.v.) antagonised the inhibition of firing induced by 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) in anaesthetised rats. (+/-)-WAY100135 antagonised the action of 5-carboxamidoiodotryptamine in the guinea-pig ileum, with a pA2 of 7.2. (+/-)-WAY100135 had no agonist-like behavioural effects but antagonised the behavioural syndrome and hypothermia induced by 8-OH-DPAT in the rat and mouse, respectively. The interaction of (+/-) WAY100135 with the 5-HT1A receptor was stereoselective; the (+)-enantiomer being markedly more active in binding, functional and behavioural studies. These data indicate that (+/-)-WAY100135 is the first highly selective antagonist at both somatodendritic and postsynaptic 5-HT1A receptors. PMID- 8365458 TI - Involvement of corticotropin-releasing factor in the antinociception produced by interleukin-1 in mice. AB - Recombinant human interleukin-1 alpha (rHu-IL-1 alpha) has been indicated to produce central antinociception in the mouse phenylquinone writhing test, the antinociception being unaffected by naloxone. Because interleukin-1 has been demonstrated to be a potent releaser of corticotropin-releasing factor (CRF) from the hypothalamus, we were interested to see whether CRF is involved in the antinociception induced by rHu-IL-1 alpha. In the present study, we examined this question using the mouse phenylquinone writhing test, in which mice were injected with various doses of CRF and/or alpha-helical CRF-(9-41), a CRF antagonist. CRF inhibited writhing responses after i.v. and intracisternal (i.c.) administration. The antinociception elicited by i.v. administered CRF was antagonized by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). The antinociception elicited by i.e. administered CRF was antagonized by i.c. injection of alpha-helical CRF-(9-41) and s.c. treatment of opioid antagonists. rHu-IL-1 alpha-induced antinociception was attenuated by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). These findings suggest that CRF possesses antinociceptive efficacy by both peripheral and central mechanisms, and that the antinociception induced by rHu-IL-1 alpha is mediated, at least in part, by the peripheral action of CRF. PMID- 8365460 TI - Teicoplanin in home therapy of the terminally ill child. AB - Children discharged in the terminal phase of illness were offered the possibility of having central venous line infections treated with teicoplanin at home by their parents after suitable instruction. The decision to begin antibiotic treatment was subjective, based on a history of rigors and/or raised temperature in an otherwise "well" child. No difficulties were encountered in instructing the chosen parents. In all, five treatment periods of 7 days were required in the five children selected. The review time was 31 weeks (mean duration, 6.2 weeks/patient; range, 4-12 weeks), ended in all cases by death. Infection occurred a mean of 3.2 weeks after discharge (range, 1-8 weeks), and all episodes were successfully treated at home without hospital admission or ward-based support. No deaths occurred as a result of antibiotic therapy failure, and there were no clinically relevant side-effects. Autopsy confirmed the absence of central venous line infection in one patient, but blood culture was positive for Staphylococcus aureus in another. This study shows that home treatment of line infections with teicoplanin is effective and well tolerated, and offers advantages in terms of quality of life and parent-child relationships. PMID- 8365459 TI - A prospective randomized study of prophylactic teicoplanin to prevent early Hickman catheter-related sepsis in patients receiving intensive chemotherapy for haematological malignancies. AB - In all, 88 patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were randomized to receive either one single bolus intravenous injection of teicoplanin, 400 mg, or no teicoplanin immediately before insertion of a double-lumen Hickman catheter. Lower incidences of catheter related Gram-positive sepsis were recorded in patients receiving prophylactic teicoplanin; exit site infection, tunnel infection and catheter-related Gram positive septicaemia were all reduced. The benefit of prophylactic teicoplanin was observed particularly among patients who were already neutropenic at the time of catheterization. All Gram-positive organisms isolated from infected skin sites or from blood cultures taken from Hickman catheters were susceptible to teicoplanin. No adverse reaction was reported in any of the patients receiving prophylaxis. Prophylactic teicoplanin, therefore, may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy, to reduce the early incidence of catheter-related sepsis, particularly during the period of neutropenia following chemotherapy. PMID- 8365462 TI - Teicoplanin in combination: role in the management of the febrile neutropenic patient. AB - The spectrum of microorganisms responsible for infection in neutropenic patients has changed in the last decade, with Gram-positive organisms now predominant. New antibiotic strategies have been required and have evolved to cope with this change. In particular, the optimal timing of glycopeptide antibiotic use has been addressed. Both teicoplanin and vancomycin are highly effective agents for susceptible Gram-positive organisms. Teicoplanin has advantages in terms of ease of administration and lower toxicity, while vancomycin has proved durable over many years' use. There are now firm indications for the use of glycopeptide antibiotics in febrile neutropenic patients, including clinically defined central venous catheter infection and microbiologically documented infection with susceptible organisms. The empirical use of the glycopeptide antibiotics in combination with other agents as first-line treatment, however, is less certain. The utility of this approach remains controversial and ultimately depends on the extent to which local practice favours the emergence of Gram-positive infections in neutropenic patients. PMID- 8365461 TI - Teicoplanin versus vancomycin in the empirical treatment of febrile neutropenic patients. AB - Gram-positive infections have become prevalent among neutropenic patients with cancer. A prospective, randomized, double-blind trial of teicoplanin, 6 mg/kg every 12 h for three doses then every 24 h, versus vancomycin hydrochloride, 15 mg/kg every 12 h, in the empirical treatment of febrile neutropenic patients was undertaken among 50 consecutive patients with haematological malignancy. The patients also received piperacillin sodium, 3 g every 4 h, and tobramycin sulphate, 1.5-2 mg/kg every 8 h. Both groups (25 teicoplanin and 25 vancomycin) were comparable in age, sex, renal function, underlying disease and concurrent therapy. Among 22 patients (44%) with culture-proven infection, Gram-positive organisms were isolated in 15 (9 with bacteraemia) and Gram-negative in 11 (4 with bacteraemia). Mixed or polymicrobial infection occurred in 8 patients. Serum 1-h peak and trough levels at steady state were 41 +/- 15 and 12 +/- 3 mg/l for teicoplanin (at 14 +/- 4 days), and 40 +/- 10 and 8 +/- 5 mg/l for vancomycin (at 0.9 +/- 0.6 days). Mean elimination half-life and apparent volume of distribution at steady state were 80.5 +/- 21.5 h and 1.4 +/- 0.8 l/kg for teicoplanin, and 5.6 +/- 1.8 h and 0.6 +/- 0.2 l/kg for vancomycin. Empirical antimicrobial therapy was successful in 23 teicoplanin and 21 vancomycin patients, respectively (p = 0.67; two-tailed Fisher's exact test). Nephrotoxicity (serum creatinine > 110 mmol/l), however, was more common among vancomycin patients (10 versus 2; p = 0.02), while termination of treatment due to adverse effects was also more common among vancomycin patients (10 versus 2; p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365463 TI - Teicoplanin in gram-positive infection: microbiological aspects. AB - The widespread use of indwelling catheters and successful antibiotic treatment of Gram-negative infections has led to an increase of Gram-positive infections in severely neutropenic patients; Staphylococcus epidermidis is predominant in these infections. The problems associated with the use of vancomycin in treating such infections can be overcome by the glycopeptide antibiotic teicoplanin. It is as effective as vancomycin, but does not cause "red man" syndrome, is uncommonly nephrotoxic, can be given as a rapid bolus once daily, and routine serum monitoring is not required. Other approaches to reducing catheter-related infections include improved training of personnel in catheter insertion and the development of new materials and methods in cannula production. PMID- 8365464 TI - 5-Methylcytosine in genes with methylation-dependent regulation. AB - An asymmetric distribution of deoxy-5-methylcytidylic acid-inhibiting restriction sites (dcm-sites) takes place in ten human genes regulated by 5-methylcytosine. These genes are dcm-site enriched upstream and dcm-site poor downstream. Along them, there is a scattering of hypermethylatable introns and hypomethylatable exons with a common code: the 5mCpG dinucleotides characterize promoters; Gp5mCs characterize introns; Tp5mCs and Cp5mCs are in small concentrations in exons. Housekeeping genes contain more dcm-sites when compared with tissue-specific genes. This depends on the higher number of dcm-sites in their promoters and introns. In exons, the relatively lower number of dcm-sites is almost the same in both housekeeping and tissue-specific genes. Going from 5' to 3', the average frequency of occurrence of these sites per nucleotide units decreases in introns and increases in exons. This difference is highly discriminated for tissue specific and less discriminated for housekeeping genes. PMID- 8365465 TI - Detection of GTP-binding proteins in barley aleurone protoplasts. AB - We report the existence of several families of GTP-binding proteins in barley aleurone protoplasts. Partial purified plasma membrane proteins were separated by SDS-PAGE, transferred to a nitrocellulose filter and incubated with either antisera raised against a highly conserved animal G protein alpha subunit peptide/or Ras protein, or with [alpha-32P]GTP. Two sets of proteins of M(r) = 32 36 kDa and 22-24 kDa were strongly recognized by the antisera. Binding of [alpha 32P]GTP was detected on Western blots with proteins of M(r) = 22-24 kDa and 16 kDa. Binding was inhibited by 10(-7)-10(-6) M GTP gamma S, GTP or GDP; binding was not affected by 10(-6)-10(-5) M ATP gamma S or ADP. The kinetics, specificity and the effects of phytohormones in a [35S]GTP gamma S binding assay were also studied in isolated plasma membranes of barley aleurone protoplasts. PMID- 8365466 TI - Constitutive over-production of DNA-damage recognition proteins and acquired UV resistance in prolonged culture of F9 teratocarcinoma stem cells. AB - An ultraviolet (UV)-resistant F9 variant cell line, termed F9Vc, was established from a prolonged culture of murine F9 embryonic stem cells. A 6-fold UV resistance was detected in F9V2 cells compared to the F9 parental cells, as determined by ID50 (36 J/m2 vs. 6 J/m2), the UV dose causing 50% growth inhibition. Using a DNA mobility-shift assay, a nuclear protein (termed UVDRP) that preferentially binds to UV-damaged DNA was detected in F9 and F9Vc cell extracts. The UVDRP in F9Vc cells was present at a 7-fold higher concentration than that of F9 cells. Interestingly, the F9 UVDRP was transiently induced following cellular differentiation by retinoic acid (RA)/cAMP, with optimum induction (15-fold) at 6 days. Although constitutively over-produced, UVDRP also remained inducible in F9Vc cells in response to RA/cAMP. Indirect DNA repair measurement by host cell reactivation of UV-damaged plasmid DNA demonstrated that F9Vc cells exhibited a slight increase or a similarity in repair ability compared to the F9 cells. Parallel experiments using the repair-defective xeroderma pigmentosum (XP) group A fibroblasts and the normal VA13 fibroblasts also indicated that over-production of UVDRP binding activity was associated with enhanced DNA repair and UV resistance. The findings indicate that prolonged culture of F9 cells can establish a condition sufficient to cause constitutive over-production of UVDRP binding activity and UV resistance. The results also suggest that the RA/cAMP-inducible UVDRP in F9 stem cells may be important for the sensitivity or resistance of the cells to UV damage. PMID- 8365467 TI - Organic acid activation of the alternative oxidase of plant mitochondria. AB - Alternative oxidase activity (oxygen uptake in the presence of KCN, antimycin or myxothiazol) in mitochondria isolated from the roots of soybean seedlings was very slow, even with succinate as substrate. This activity was stimulated substantially (100-400%) by the addition of pyruvate, with half maximal stimulation occurring at 0.1 mM pyruvate. Mitochondria from soybean shoots displayed high alternative oxidase activity with succinate and malate as substrates but lower activity with exogenous NADH; addition of pyruvate stimulated the activity with NADH up to that seen with succinate. This stimulation of cyanide-insensitive NADH oxidation was seen also with mitochondria from other species. Hydroxypyruvate and oxoglutarate could substitute for pyruvate, although higher concentrations were required to achieve maximum stimulation. Pyruvate stimulation of cyanide-insensitive oxygen uptake was observed with exogenous quinols as substrates, with sub-mitochondrial particles, and in the presence of the pyruvate transport inhibitor, cyanohydroxycinnamic acid, but was not observed with detergent-solubilised mitochondria. It is suggested that pyruvate acts allosterically on the alternative oxidase to stimulate its activity. The implications of these findings for respiration in vivo are discussed. PMID- 8365468 TI - Lysophosphatidic acid induces tyrosine phosphorylation and activation of MAP kinase and focal adhesion kinase in cultured Swiss 3T3 cells. AB - Lysophosphatidic acid (LPA) added to serum-starved Swiss 3T3 cells induced, in a time- and concentration-dependent manner, tyrosine phosphorylation of multiple proteins, including proteins of 43, 64, 88 kDa and a group of proteins between 110 and 130 kDa. Among them, two proteins, p43 and p120, were identified as mitogen-activated protein kinase (MAP-kinase) and focal adhesion kinase (FAK), respectively, by immunoprecipitation and immunoblot analysis. Tyrosine phosphorylation of p64 peaked at 1 min and declined rapidly, whereas that of MAP kinase and FAK peaked at 5 and 10 min after the addition of LPA, respectively. The activity of MAP-kinase determined as phosphorylation of myelin basic protein increased transiently about 3-fold at 5 min, and correlated with tyrosine phosphorylation. These results indicate that tyrosine phosphorylation of these proteins is a part of the signal transduction by LPA and may be involved in its mitogenic responses. PMID- 8365469 TI - Cyclin E enhances P53-mediated transactivation. AB - Plasmids expressing G1 and G2 cyclins were introduced into the Saos-2 cell system monitoring p53-mediated transactivation [(1993) Oncogene 8, 543]. Cyclin E, but not other cyclins, enhanced the p53-mediated transactivation about 2-fold. Co transfection of a CDK2 expression plasmid caused a 30% increase in the extent of the p53-mediated transactivation. Moreover, the transfected p53 protein became phosphorylated coordinately with the enhanced transactivation. The close correlation between transactivation and p53 phosphorylation suggests that phosphorylation is involved in positive regulation for the transactivation by p53. PMID- 8365470 TI - The hinge region of chicken annexin I contains no site for tyrosine phosphorylation. AB - Annexin I (AnxI) is a calcium-dependent membrane binding protein which has been implicated in various physiological activities. The region of the chicken anxI cDNA encoding the first 130 amino terminal residues was cloned by reverse transcription PCR in order to determine the relationship of its variable amino terminal regulatory region with other known annexins. This nucleotide sequence shows 86% identity with pigeon AnxI isoforms, and 57% with its human homolog. The protein encoded by the chicken anxI cDNA lacks the canonical epidermal growth factor receptor/kinase phosphorylation site, which is present in AnxI of other species. In contrast, the putative protein kinase C phosphorylation site of the amino-terminus is present in the chicken AnxI. Whereas the pigeon genome contains two anxI genes, genomic Southern analysis shows that in the chicken AnxI is encoded by only a single gene. These data suggest that AnxI has undergone significant sequence variation in the avians, and clarifies the relationships of the avian anxI genes with their ancestral homologs. PMID- 8365471 TI - Rapid binding of synapsin I to F- and G-actin. A study using fluorescence resonance energy transfer. AB - Synapsin I is a nerve terminal phosphoprotein which interacts with synaptic vesicles and actin in a phosphorylation-dependent manner. By using fluorescence resonance energy transfer between purified components labeled with fluorescent probes, we now show that the binding of synapsin I to actin is a rapid phenomenon. Binding of synapsin I to actin can also be demonstrated when synaptic vesicles are present in the medium and appears to be modulated by ionic strength and synapsin I phosphorylation. PMID- 8365472 TI - The in situ degradation of ceramide, a potential lipid mediator, is not completely impaired in Farber disease. AB - The time course of degradation of a radiolabelled natural ceramide has been studied in intact, living lymphoid cells and skin fibroblasts from normal individuals and from patients affected with Farber disease, an inborn disorder of ceramide metabolism due to deficient activity of lysosomal ceramidase. The hydrolysis of ceramide in lysosomes was selectively followed by examining the turnover of an LDL-associated radioactive sphingomyelin. This permitted to estimate accurately the effective lysosomal ceramidase activity and to demonstrate: (i) a very active catabolism of ceramide in normal cells; and (ii) the absence of a complete block of ceramide degradation in Farber cells. The possible implication of ceramide as a lipid mediator of the pathogenesis of Farber disease is discussed. PMID- 8365473 TI - Phosphorylation of GDI and membrane cycling of rab proteins. AB - Membrane transport is known to be regulated by protein phosphorylation and by small GTPases of the rab family. Using specific antibodies, we have identified a 55 kDa phosphorylated protein which co-immunoprecipitated with the cytosolic forms of rab5 and other rab proteins. We demonstrate, on the basis of its mobility in two-dimensional electrophoresis gels and its immunological properties, that this protein is rab GDI (p55/GDI). We also found that, a minor fraction of p55/GDI is membrane associated, but, whilst also complexed with rab proteins, it is not phosphorylated. On the basis of these data we suggest that the cycling of rab proteins between membranes and cytosol is regulated by phosphorylation of p55/GDI. PMID- 8365474 TI - Energy transfer processes in Rhodopseudomonas palustris grown under low-light conditions. Heterogeneous composition of LH 2 complexes and parallel energy flow pathways. AB - Excitation energy flow in the purple photosynthetic bacterium Rhodopseudomonas palustris grown under a low-light intensity was studied by time-resolved fluorescence spectroscopy in the ps time range. This bacterium synthesized the B824 component under this light condition. Time-resolved spectra at 20 degrees C indicated the sequential energy flow in the order of B803, B856, B882 and B900, long wavelength antenna. An emission from B803 was not observed. A remarkable feature was the emission from B824 throughout the measuring time. After the excitation pulse of 100 ps, the spectra did not change any further, indicating the establishment of an equilibrium among components. Based on the energy distribution after equilibrium, parallel energy transfer pathways to LH 1 were suggested; one including B824 integrated in the B803-824-856 complex, and the other, from the B803-856 complex to B882. The latter was the dominant energy flow pathway in this bacterium. PMID- 8365475 TI - Identification of a novel protein kinase C inhibitor in microsomes from phytohaemagglutinin activated human peripheral blood mononuclear cells. AB - A peptide inhibiting either corpuscolate or purified PKC has been identified from microsomes of PHA-activated human PBMC but it is not detectable in microsomes of resting PBMC. The peptide was obtained from a microsomal preparation in an oligomeric form that could be transformed into a monomeric form by beta-MSH. The active peptide (IN) was retained on a PC-11 chromatographic column and could be eluted with NaCl. IN is ineffective on PKC-dependent protamine phosphorylation of protamine and on Ca2+ and phospholipid-independent activity generated by mild hydrolysis with trypsin of PKC. Ca2+ binding is permissive for IN activity. IN inhibits particulate PKC in PHA-activated PBMC, but is ineffective after TPA activation. All these data indicate that IN acts at the regulatory domain of PKC. PMID- 8365476 TI - Identification of the gene encoding the activator of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans by gene expression in Escherichia coli. AB - (R)-2-Hydroxyglutaryl-CoA dehydratase (HGDA/B) from Acidaminococcus fermentans requires an activator protein for activity. This activator (HGDC) has not yet been purified from its natural source due to its low concentration combined with an extreme sensitivity towards oxygen. Gene expression in Escherichia coli identified an open reading frame (780 bp) as the gene encoding HGDC. Dehydratase activity was stimulated at least tenfold by cell-free extracts of E. coli cells transformed with a plasmid carrying hgdC. On the chromosome the hgdC gene is located just before hgdA and hgdB. PMID- 8365477 TI - Complete amino acid sequence of puroindoline, a new basic and cystine-rich protein with a unique tryptophan-rich domain, isolated from wheat endosperm by Triton X-114 phase partitioning. AB - A new basic protein has been isolated from wheat endosperm by Triton X-114 phase partitioning. It contains five disulfide bridges and is composed of equal amounts of a polypeptide chain of 115 amino acid residues and of the same chain with a C terminus dipeptide extension. The most striking sequence feature is the presence of a unique tryptophan-rich domain so that this protein isolated from wheat seeds has been named puroindoline. The similar phase partitioning behavior in Triton X 114 of this basic cystine-rich protein and of purothionins suggests that puroindoline may also be a membranotoxin that might play a role in the defense mechanism of plants against microbial pathogens. PMID- 8365478 TI - Thrombospondin (TSP1) mediates in vitro proliferation of human MG-63 osteoblastic cells induced by alpha-thrombin. AB - Thrombospondin (TSP) is a 450-kDa glycoprotein synthesized and secreted by human MG-63 osteoblastic cells. In this study, we have first studied the effect of alpha-thrombin on TSP expression by human MG-63 cells. In situ hybridization indicated that TSP mRNA level in thrombin-treated MG-63 cells was increased when compared to unstimulated cells. As judged by immunofluorescence, thrombin treatment of MG-63 cells resulted in increased cell surface expression of TSP when compared to quiescent cells. Because thrombin stimulates proliferation of osteoblastic cells, the involvement of TSP in proliferation of thrombin stimulated osteoblastic cells was then investigated using a serum-free mitogenesis assay. Both alpha-thrombin (0.01 to 0.15 U/ml) and TSP (5 to 600 ng/ml) caused a dose-dependent increase in [3H]thymidine incorporation by MG-63 cells. Proliferation of osteoblastic cells induced by alpha-thrombin or TSP was specifically and totally inhibited by anti-TSP monoclonal antibodies (3-10 micrograms/ml) or by indomethacin (1 microM), an inhibitor of prostaglandin synthesis. Anti-TSP antibodies which inhibited cell proliferation also inhibit TSP expression to the surface of these cells. Our experiments support the existence of a mechanism whereby TSP bound to the cell surface of thrombin treated MG-63 cells stimulates secretion of prostaglandins which, in turn, allow cell proliferation to proceed. PMID- 8365479 TI - Production of recombinant antibodies in lymphoid and non-lymphoid cells. AB - A recombinant tandem of 'chimeric' mouse/human immunoglobulin (Ig) genes was constructed and inserted into plasmid pGEM1 under the control of the T7 bacteriophage RNA polymerase promoter. Lymphoid (Sp2/0) and non-lymphoid (CHO) cell lines used for transfection contained in their genomes a semisynthetic gene of T7 RNA polymerase and steadily expressed this enzyme. It was shown for the first time that a stable polycystronic transcription of the Ig gene tandem occurs under the control of a single T7 phage promoter, both in lymphoid and non lymphoid cells. Synthesis of kappa-light and epsilon-heavy Ig chains and functionally active antibodies was observed in the above-mentioned transfected cell lines. PMID- 8365480 TI - Staurosporine-related compounds, K252a and UCN-01, inhibit both cPKC and nPKC. AB - The potent inhibitors of protein kinase C (PKC), H7, staurosporine, and staurosporine derivatives, were examined for their inhibitory effects on novel PKC (nPKC) isozymes delta and epsilon. H7 and staurosporine, usually used as selective inhibitors of PKC, showed similar inhibitory effects on cPKC (a mixture of cPKC alpha, beta, and gamma) and nPKC delta and epsilon. The inhibitory effects of K252a, a non-selective protein kinase inhibitor, on cPKC was 3.2- and 22-fold higher than those on nPKC epsilon and delta, respectively. The staurosporine derivatives UCN-01 and UCN-01-Me also showed selective inhibition of cPKC. PMID- 8365481 TI - cDNA isolation and partial gene structure of the human alpha 4(IV) collagen chain. AB - A novel collagen IV chain, alpha 4(IV), has recently been identified in basement membranes. We describe part of the primary structure of the human alpha 4(IV) polypeptide for the first time, which has been determined by cloning and sequencing of cDNAs encoding 241 amino acid residues of the COL domain and 231 residues of the NC1 domain. We also characterized a genomic DNA fragment containing 4 exons coding for the entire NC1 domain. Among five known alpha chains of collagen IV, the alpha 4(IV) chain is distinct from the other four chains. However, it is more similar to the alpha 2(IV) chain than to the alpha 1(IV), alpha 3(IV) and alpha 5(IV) chains in terms of amino acid sequence homology, domain structure of polypeptides and exon/intron structure of the genes, suggesting the presence of two phylogenetically distinct subclasses of collagen IV alpha chains; one composed of alpha 2 and alpha 4 chains and the other of alpha 1, alpha 3 and alpha 5 chains. PMID- 8365482 TI - Fluorescence quenching at interfaces and the permeation of acrylamide and iodide across phospholipid bilayers. AB - Studies of fluorescence quenching in membrane proteins are complicated by the fact that the barrier effect of the bilayer towards the quenchers is not known with precision. Our studies show that (a) both acrylamide and iodide can permeate the membrane at comparable rates, (b) when quenchers are added externally to a vesicle suspension, the apparent Stern-Volmer quenching constants for the same fluorophores are lower in the inner than in the outer aqueous compartments, and (c) at least some non-polar fluorophores embedded in the bilayer are quenched by iodide, but not by acrylamide. PMID- 8365483 TI - Modification by site-directed mutagenesis of the specificity of Erythrina corallodendron lectin for galactose derivatives with bulky substituents at C-2. AB - Examination of the three-dimensional structure of Erythrina corallodendron lectin (ECorL) in complex with a ligand (lactose), the first of its kind for a Gal/GalNAc-specific lectin [(1991) Science 254, 862-866], revealed the presence of a hydrophobic cavity, surrounded by Tyr108 and Pro134-Trp135, which can accommodate bulky substituents such as acetamido or dansylamido (NDns) at C-2 of the lectin-bound galactose. Comparison of the primary sequence of ECorL with that of soybean agglutinin, specific for galactose and its C-2 substituted derivatives, and of peanut agglutinin, specific for galactose only, showed that in soybean agglutinin, Tyr108 is retained, and Pro134-Trp135 is replaced by Ser Trp, whereas in peanut agglutinin, the former residue is replaced by Thr and the dipeptide by Ser-Glu- Tyr-Asn. Three mutants of ECorL were therefore constructed: L2, in which Pro134-Trp135 was replaced by Ser-Glu-Tyr-Asn; Y108T, in which Tyr108 was replaced by Thr and the double mutant L2; Y108T. They were expressed in Escherichia coli, as done for recombinant ECorL [(1992) Eur. J. Biochem. 205, 575-581]. The mutants had the same hemagglutinating activity as native or rECorL. Their specificity for galactose, GalNAc and Me beta GalNDns was examined by inhibition of hemagglutination and of the binding of the lectin to immobilized asialofetuin; in addition, their association constants with Me alpha GalNDns and Me beta GalNDns were measured by spectrofluorimetric titration. The results showed that Y108T had essentially similar specificity as the native and recombinant lectins. The affinity of L2 and L2;Y108T for galactose was also the same as ECorL, but they had a lower affinity for GalNAc and markedly diminished affinity for the dansyl sugars (up to 43 times, or 2 kcal, less). This appears to be largely due to steric hindrance by the two additional amino acids present in the cavity region in these mutants. Our findings also provide an explanation for the inability of PNA to accommodate C-2-substituted galactose derivatives at its primary subsite. PMID- 8365484 TI - Cloning and expression of a novel human profilin variant, profilin II. AB - We have isolated a 1.7 kbp cDNA encoding a 140 amino acid protein (15.1 kDa, pI 5.91) with a high sequence similarity (62%) to human profilin (profilin I). We have termed this variant profilin II. Northern blot analysis showed that profilin II is highly expressed in brain, skeletal muscle and kidney and less strongly in heart, placenta, lung and liver. In addition, three different transcript lengths were detected. Only one transcript of profilin I was found. The expression level of this was low in brain and skeletal muscle, medium in heart and high in placenta, lung, liver and kidney. PMID- 8365485 TI - Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. AB - The rate-limiting step in the formation of prostanoids is the conversion of arachidonic acid to prostaglandin H2 by cyclooxygenase, also known as prostaglandin G/H synthase/cyclooxygenase. Two forms of cyclooxygenase have been characterized: a ubiquitously expressed form (COX-1) and a recently described second form (COX-2) inducible by various factors including mitogens, hormones, serum and cytokines. Here we quantitate by the reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of COX-1 and COX-2 mRNA in human tissues including lung, uterus, testis, brain, pancreas, kidney, liver, thymus, prostate, mammary gland, stomach and small intestine. All tissues examined contained both COX-1 and COX-2 mRNA and could be grouped according to the level of COX mRNA expression. The highest levels of COX mRNAs were detected in the prostate where approximately equal levels of COX-1 and COX-2 transcripts were present. In the lung high levels of COX-2 were observed whereas COX-1 mRNA levels were about 2 fold lower. An intermediate level of expression of both COX-1 and COX-2 mRNA was observed in the mammary gland, stomach, small intestine, and uterus. The lowest levels of COX-1 and COX-2 mRNA were observed in the testis, pancreas, kidney, liver, thymus, and brain. PMID- 8365486 TI - cDNAs sequences encoding cytochrome P450 (CYP71 family) from eggplant seedlings. AB - Three cytochrome P450 (P450) cDNAs were isolated from an eggplant hypocotyl cDNA library using eggplant CYP75 cDNA as a probe. These cDNAs have greater than 65% identity in their amino acid sequences, indicating that they belong to the same family. Comparison of these with P450 proteins from other sources showed that the protein with the greatest degree of homology is CYP71, isolated from avocado fruits (approximately 48%). We concluded that they are novel members of the CYP71 gene family (CYP71A2, 3 and 4). We have examined the level of mRNA transcripts from the CYP71 family in eggplant hypocotyl tissues and petunia flower buds, and found that the level of transcripts is developmentally regulated in the flower bud. PMID- 8365487 TI - Prooxidant role of vitamin E in copper induced lipid peroxidation. AB - When exposed to Cu2+, alpha-tocopherol, in detergent dispersion, is rapidly oxidised. Moreover, if phospholipids and traces of their hydroperoxide derivatives are included in these dispersions, Cu2+ initiates lipid peroxidation, the rate of which is dramatically stimulated by alpha-tocopherol. The observation that the rate of alpha-tocopherol consumption is identical in the absence and in the presence of lipids undergoing peroxidation, apparently rules out any antioxidant effect. These results are consistent with a prooxidant effect of vitamin E, mediated by its capability to reduce Cu2+ to Cu+ which, in turn, produces, from lipid hydroperoxides, the highly reactive alkoxyl radicals. Present data highlight the risk of misleading results in interpreting the significance of lags in peroxidation of LDL challenged with Cu2+. PMID- 8365488 TI - The conformation of tRNA genes. Chemical modification studies. AB - It has been suggested that eukaryotic tRNA genes might adopt a higher order stem and loop structure to facilitate transcription by interaction of their variably spaced intragenic promoter blocks. Using sodium bisulphite, which reacts specifically with cytosine residues in single-stranded nucleic acids, no deamination of C in the TTCGAA sequence of the 3' ICR of a tRNA(Leu) gene could be detected under conditions which caused 60% deamination of cytosine residues within the loop region of a synthetic cruciform cloned in the same negatively supercoiled plasmid vector. We conclude that, under these conditions, such structures occur in tRNA genes very rarely, if at all. PMID- 8365489 TI - Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor. AB - Peroxynitrite is an oxidant which could be formed in the vasculature by the reaction of superoxide with nitric oxide. It is capable of modifying amino acid residues and of initiating lipid peroxidation. In the present study we have shown that peroxynitrite converts low density lipoprotein to a form recognized by the macrophage scavenger receptor and that this process is associated with modification of the protein and lipid, and with the oxidation of alpha-tocopherol to alpha-tocopherol quinone. PMID- 8365490 TI - Primary structure of the 5 S subunit of transcarboxylase as deduced from the genomic DNA sequence. AB - Transcarboxylase from Propionibacterium shermanii is a complex biotin-containing enzyme composed of 30 polypeptides of three different types. It is composed of six dimeric outer subunits associated with a central cylindrical hexameric subunit through 12 biotinyl subunits; three outer subunits on each face of the central hexamer. Each outer dimer is termed a 5 S subunit which associates with two biotinyl subunits. The enzyme catalyzes a two-step reaction in which methylmalonyl-CoA and pyruvate form propionyl-CoA and oxalacetate, the 5 S subunit specifically catalyzing one of these reactions. We report here the cloning, sequencing and expression of the monomer of the 5 S subunit. The gene was identified by matching amino acid sequences derived from isolated authentic 5 S peptides with the deduced sequence of an open reading frame present on a cloned P. shermanii genomic fragment known to contain the gene encoding the 1.3 S biotinyl subunit. The cloned 5 S gene encodes a protein of 519 amino acids, M(r) 57,793. The deduced sequence shows regions of extensive homology with that of pyruvate carboxylase and oxalacetate decarboxylase, two enzymes which catalyze the same or reverse reaction. A fragment was subcloned into pUC19 in an orientation such that the 5 S open reading frame could be expressed from the lac promoter of the vector. Crude extracts prepared from these cells contained an immunoreactive band on Western blots which co-migrated with authentic 5 S and were fully active in catalyzing the 5 S partial reaction. We conclude that we have cloned, sequenced and expressed the monomer of the 5 S subunit and that the expressed product is catalytically active. PMID- 8365491 TI - Interaction of GTP-binding protein Gq with photoactivated rhodopsin in the photoreceptor membranes of crayfish. AB - Interaction of G-protein with photoactivated rhodopsin (Rh*) in crayfish photoreceptor membranes was investigated by immunoprecipitation using an antibody against rhodopsin. Two kinds of protein were co-precipitated with rhodopsin. One is an alpha subunit of class-q G-protein (42 kDa, CGq alpha) which showed light induced, dose-dependent binding to rhodopsin, and the other is an actin-like protein (44 kDa) with light-independent binding. Most of the CGq alpha was available for binding to Rh* but was dissociated from Rh* in the presence of GTP gamma S. These findings demonstrate that, in the crayfish photoreceptor, a Gq class of G-protein is activated by Rh*. PMID- 8365492 TI - A novel ryanodine sensitive calcium release mechanism in cultured human myometrial smooth-muscle cells. AB - In cultured human myometrial cells application of caffeine (1-30 mM) did not result in an elevation of intracellular Ca2+ ([Ca2+]i). Caffeine was found to reversibly inhibit both spontaneous and agonist-induced repetitive rises in [Ca2+]i possibly as a consequence of its ability to interfere with the binding of inositol trisphosphate (IP3) to the receptor on the sarcoplasmic reticulum. Brief applications of ryanodine (1-10 microM) were observed to elevate [Ca2+]i and repeated exposures to ryanodine could elicit Ca2+ transients of similar magnitude. Ryanodine was also observed to mobilise Ca2+ in cells bathed in nominally Ca(2+)-free solution. These observations suggest the presence of a novel type of ryanodine-sensitive Ca(2+)-induced Ca2+ release (R-CICR) system in human myometrial cells. PMID- 8365493 TI - Compartmentation of inorganic phosphate in perfused rat liver. Can cytosol be distinguished from mitochondria by 31P NMR? AB - Compartmentation of inorganic phosphate was studied in intact perfused rat liver at 4 degrees C by 31P NMR. It was shown that decreases in cytosolic pH or cytosolic Pi concentration induced the appearance of an additional Pi resonance at low field which was assigned to Pi from an alkaline compartment. Valinomycin (K+ ionophore) induced a further splitting of the lines whereas nigericin (K+/H+ antiport) or potassium cyanide (inhibitor of cytochrome oxidase) had opposite effects. As valinomycin acts mainly on the cytosolic/mitochondrial K+ gradient and KCN on the mitochondrial respiratory chain, it was deduced that the alkaline compartment as revealed by the second Pi resonance was probably mitochondria. Single Pi lines observed on perchloric extracts of livers exhibiting two resonances during cold perfusion confirmed that the split peaks in the intact liver indeed arose from the same molecular species. PMID- 8365494 TI - A complex of rab3A, SNAP-25, VAMP/synaptobrevin-2 and syntaxins in brain presynaptic terminals. AB - Two monoclonal antibodies (SPM-1 and SPM-2) immunoprecipitate brain N-type calcium channels. On immunoaffinity chromatography of digitonin extracts of bovine brain membranes on SPM-1- and SPM-2-Sepharose, proteins of 36 (syntaxins A and B), 28 and 19 kDa are specifically retained by both columns. Here we show that the 19 and 28 kDa bands contain VAMP/synaptobrevin-2, and rab3A/smg25A and SNAP-25, respectively. Since SPM-1 and SPM-2 recognize only syntaxins and the 28 kDa band (rab3A/sm25A and SNAP-25), respectively, the results indicate that all these proteins form a complex. Our results suggest tight linkage between the components involved in neurotransmitter release. PMID- 8365495 TI - A comment on: 'Homology of the NifS family of proteins to a new class of pyridoxal phosphate-dependent enzymes', by Christos Ouzounis and Chris Sander (1993) FEBS Lett. 322, 159-164. PMID- 8365496 TI - The American Fertility Society conjointly with The Canadian Fertility and Andrology Society. Montreal, Quebec, Canada, October 11-14, 1993. Abstracts. PMID- 8365497 TI - [The renin-angiotensin system and blood pressure]. AB - The renin-angiotensin system plays an important role in the regulation of blood pressure. Recent progress in molecular biology enables us to investigate the molecular mechanism of essential hypertension. Accumulating data suggest that the disorder of the renin-angiotensin system is not essentially a primary factor of hypertension, but it apparently plays an indispensable role in the pathogenesis of hypertension. Many researchers including us have shown that the renin angiotensin system also contributes the development of various hypertension related organ damages by its hypertrophic, vasculotoxic or unknown mechanisms. Gene diagnosis and newly developed antihypertensive drug therapy including gene therapeutics will open the new era of individualized and etiology-based hypertension treatment. PMID- 8365498 TI - [Parenteral replacement of 1-T4 in hypothyroid patients with esophageal stenosis and unconsciousness]. AB - Hypothyroid patients are usually treated with in an oral administration of 1-T4. When oral administration is impossible because of esophageal stenosis or unconsciousness in such patients, parenteral replacement is required. We prepared a solution of 1-T4 50 micrograms/ml for intravenous administration in Tohoku University Hospital as follows: 5mg of 1-T4 (Nakarai Co.) was dissolved in 1ml of 0.1N NaOH and diluted with 0.9% NaCl and sterilized with membrane filter. Two patients with esophageal stenosis due to thyroid cancer and esophageal cancer and one in a coma due to adrenal crisis had replacement with intravenous 1-T4. Initial doses of 12.5 micrograms or 25 micrograms diluted with 100ml of 0.9% NaCl containing 1% albumin were given by drip infusion. Every week 12.5 micrograms or 25 micrograms of 1-T4 was increased. By replacement of low doses, 50 micrograms or 75 micrograms, serum T4 reached a normal level. No adverse action was observed during or after parenteral replacement. The preparation of 1-T4 was stable at least for one year and 11 months. Parenteral replacement of T4 is a useful and safe method for patients who are unable to take drugs orally. PMID- 8365499 TI - [Studies on the in vitro binding assay of androgen receptor in rat skeletal muscle]. AB - It is known that some athletes use androgenic anabolic steroids to promote skeletal muscular strength and muscle hypertrophy in response to muscle strength training. However, it is not defined whether anabolic steroids are effective for muscle hypertrophy. In order to make this question clear, we examined the conditions of a binding assay of cytosolic androgen receptor on rat skeletal muscle as the first step. We used 3H-mibolerone as the ligand for specific binding to the androgen receptor. The following conditions of the assay were examined in this study: the incubation temperature and time, concentration of 3H mibolerone, the effects of monothioglycerol and triamcinolone acetonide, and the effect of repeated freezing and thawing of the samples on binding. It was a suitable condition for an androgen receptor assay that samples prepared from unfrozen fresh muscle were incubated with 16nM 3H-mibolerone at 4 degrees C for 20 hrs, with monothioglycerol (20mM) and triamcinolone acetonide (25 microM) added. Using these assay conditions, we measured the binding capacity of androgen receptor in rat skeletal muscles. The values of Kd and Bmax in M. gastrocnemius were 3.61 +/- 0.60 x 10(-9)M and 3.18 +/- 2.23fmol/mg protein respectively. PMID- 8365500 TI - [Iodination and binding characteristics of 125I-d(CH2)5 [Tyr(Me)2, Tyr(NH2)9] AVP]. AB - With iodinated vasopressin analogue, d(CH2)5[Tyr(Me)2, Tyr(NH2)9] AVP, at position 9, followed by purification by HPLC (specific activity 473-543Ci/mmol), a specific binding was observed in the rat liver plasma membrane fraction. Scatchard analysis indicated a single class of high-affinity binding sites with a Kd of 0.23nM and Bmax of 142fmol/mg protein. V2-agonist, DDAVP, did not displace 125I-vasopressin analogue. These results suggest that 125I-d(CH2)5[Tyr(Me)2, Tyr(NH2)9] AVP with a high specific activity is a useful tool to investigate V1 receptors. PMID- 8365501 TI - [Relative lymphopenia in Cushing's syndrome]. AB - The differential white blood cell (WBC) count often reveals relative lymphopenia in Cushing's syndrome and may be a clue to the discovery of the ailment. However, the incidence of this finding has rarely been reported in the literature. We conducted a study on 40 patients with Cushing's syndrome due to adrenocortical adenoma to evaluate the diagnostic implications of relative lymphopenia. Total WBC count, differential WBC count, basal level of plasma cortisol, urinary excretion of free cortisol and thyroid function were evaluated preoperatively. We also investigated the differential WBC count in 40 patients with thyroid tumors matched for age and sex with the Cushing's syndrome patients. The proportion of lymphocytes among WBCs was also compared between the two groups. The proportion of lymphocytes among WBCs was significantly lower in the patients with Cushing's syndrome (19.4 +/- 10.8%) than in those with thyroid tumors (42.3 +/- 9.5%, mean +/- SD, p < 0.05). The incidence of relative lymphopenia was high (82.5%) as well as that of increased urinary excretion of free cortisol (85.3%) in Cushing's syndrome patients. The low T3 syndrome was frequently seen (73.9%), whereas the incidences of leukocytosis and an increased level of basal plasma cortisol were relatively low (42.5% and 47.5%, respectively). Relative lymphopenia provides useful information for diagnosing Cushing's syndrome since it has high sensitivity although it should be kept in mind that its specificity is low. PMID- 8365502 TI - Update on oral contraception. PMID- 8365503 TI - Clinical utility of CA 125 in preoperative diagnosis of patients with pelvic masses. AB - The preoperative prediction of whether a pelvic mass is benign or malignant is of great clinical use. Ultrasound examinations have become increasingly popular but despite this remains problematic. It is discussed whether or not preoperative serum CA 125 levels may be of value in differentiating between a benign and a malignant pelvic mass. When the results of the CA 125 assay are added to any other diagnostic test in the postmenopausal patient, predictive values approach 100%. Utilizing CA 125 levels, a workup scheme may be developed and an operative intervention may be in order based on a high degree of preoperative diagnostic accuracy. PMID- 8365504 TI - CA 125 in the management of endometriosis. AB - CA 125 is expressed by eutopic and ectopic endometrium. In women with advanced endometriosis, plasma concentrations are increased towards the end of the luteal phase and during menstruation but not during the follicular and early luteal phases. In women without endometriosis, such cyclic changes of CA 125 in plasma are not observed. In women with cystic ovarian endometriosis, plasma CA 125 concentrations are markedly elevated. Measurement of CA 125 in ovarian cyst fluid is the method of choice to differentiate a cystic corpus luteum from an ovarian endometriotic cyst, a frequent and difficult clinical problem. CA 125 can be used to diagnose deeply infiltrating endometriosis with a sensitivity of 36% and a specificity of 87%. These figures underestimate the clinical importance, since plasma CA 125 concentrations are mainly important for the diagnosis of deeply infiltrating endometriosis types II and III, which are the most severe forms and which are clinically easily missed. Because of the strong association of deep endometriosis and pelvic pain, the assay of CA 125 in plasma may be advocated in all women with unexplained pelvic pain as an aid in the diagnosis of deeply infiltrating endometriosis. Following surgical excision of endometriosis, CA 125 can be used to monitor the completeness of surgery. PMID- 8365505 TI - CA 125 in gynecological pathology--a review. AB - The original CA 125 serum tumor marker test is a homologous double-determinant (OC 125 monoclonal antibody based) assay for the quantification of tumor associated mucin-like CA 125 molecules present in the serum. Commercial kits, now supplied by various manufacturers (and in different versions, e.g. IRMA, EIA, etc.) are currently widely applied in the following clinical situations: (i) Monitoring of disease. Doubling or halving of CA 125 serum values correlated (in 87% of all cases) with tumor progression or regression, respectively. (ii) Early prediction of outcome. Deviation from the ideal CA 125 regression curve predicts poor outcome within 3 months of cytostatic treatment. (iii) Tumor status after completion of therapy. Patients with CA 125 > 35 U/ml have (in 95% of all cases) still tumor present (at second look surgery). However, patients with CA 125 < 35 U/ml have in 50% (mostly minimal) residual disease. (iv) Early detection of recurrence. After a complete remission, a rise in CA 125 precedes tumor recurrence in 75% of all patients, with lead times up to more then 1 year, surpassing the CT-scan in cheapness and accuracy. (v) Diagnosis and differential diagnosis. Only when used in combination with other markers, do CA 125 determinations have a value as a diagnostic adjunct in the discrimination of ovarian cancer patients from those with benign ovarian tumors and from those with advanced colon cancer. Today, optimal management of ovarian cancer patients can only be provided using the CA 125 serum test. PMID- 8365506 TI - The 3-keto-desogestrel/ethinylestradiol ring: a new parenteral form of hormonal contraception. PMID- 8365508 TI - Pelvic infections and infertility. PMID- 8365507 TI - Contraception: traditional and religious attitudes. PMID- 8365509 TI - HIV infection in women. PMID- 8365510 TI - Chlamydia trachomatis--a major threat to reproduction. PMID- 8365511 TI - Transvaginal color Doppler in the assessment of placental blood flow. AB - A cross-sectional transvaginal color and pulsed Doppler study was performed on 95 normal singleton pregnancies to establish blood flow characteristics of maternal and placental components of circulation. During the pregnancy, vascular impedance to blood flow decreases from the main uterine artery to the spiral arteries in the maternal component of uteroplacental circulation. In the placental component of circulation, vascular impedance decreases from the umbilical artery to the fetal arteries within placenta-intraplacental arterioles. At the same time, in both components of uteroplacental circulation, an increase of blood flow velocity with gestational aging was observed. There was no significant drop of vascular impedance of blood flow or increase of blood flow velocity around the 12th or 14th gestational week, which should prove the hypothesis of 'opening' of spiral arteries which have tips plugged with trophoblast tissue. PMID- 8365513 TI - Screening for ovarian cancer by transvaginal sonography and colour Doppler. PMID- 8365512 TI - Melatonin: a contraceptive for the nineties. AB - The hypothalamic GnRH pulse generator activates the pituitary-gonadal reproductive axis, and contraceptive techniques have advanced to the point where GnRH analogues can block this effect. However, nature has an even finer form of contraception, whereby the GnRH pulse generator is activated or inactivated at different seasons of the year. Darkness affects the retino-pineal nervous pathway to cause the synthesis and release of melatonin from the pineal gland at night. The duration of the night time release of melatonin is longer in winter than in summer; and it is the prolongation in the duration of the night time release of melatonin, with the change of season from summer to winter, which acts as the endocrine signal for inactivating the hypothalamic GnRH pulse generator. Humans are not seasonal breeders, and evidence is presented to indicate that this is due to an impairment of the retino-pineal pathway rather than an impairment of melatonin hypothalamic function. Thus the way is open for utilising melatonin as a human contraceptive, and a melatonin-based contraceptive is at present undergoing phase III clinical trials. The challenge is to develop more refined methods for administering (or releasing) melatonin, so that it has a night time amplitude and duration which mimics that seen in long day breeders. PMID- 8365514 TI - Replacing diagnostic curettage by vaginal ultrasound. AB - Dilatation and curettage has for many years been the method of choice for diagnosing endometrial cancer in postmenopausal women. However, less than 10% of women with postmenopausal bleeding have an endometrial cancer. Vaginal sonography for measuring endometrial thickness, has in several studies proved to be a sensitive diagnostic method for diagnosing endometrial pathology. Our studies as well as others have shown that an endometrial thickness of 4 mm or less (including both endometrial layers) indicates a very low risk for endometrial carcinoma as well as any other major endometrial pathology in women with postmenopausal bleeding. Since vaginal sonography is such a simple and a non invasive diagnostic method, it thus seems reasonable that vaginal sonographic assessment of the endometrium should be the primary method for excluding any endometrial abnormality in a woman with postmenopausal bleeding. PMID- 8365515 TI - Effect of antihormones on endometrial receptors and protein secretion. AB - The antiestrogen tamoxifen and the antiprogestin RU 486 both interact with respective hormones at the receptor level, RU 486 as a pure antagonist which inhibits endometrial development, the downregulation of estrogen and progesterone receptors and the production of endometrial protein, such as PP14, during the secretory phase of the menstrual cycle. Tamoxifen, on the other hand, has both agonistic and antagonistic action. PMID- 8365516 TI - The early detection and assessment of endometrial cancer by transvaginal colour Doppler ultrasonography. PMID- 8365517 TI - Early detection of endometrial cancer by transvaginal color Doppler. AB - The present study aimed at evaluating the possibility of using transvaginal color Doppler sonography in early detection of endometrial cancer. This method was performed on 276 patients with uterine tumors before hysterectomy. Neovascularization was detected in 167 (67%) benign masses, while all malignant masses (26) were vascularised. The final diagnosis was made following pathological examination. Tumoral arterial blood flow was detected in all (26) patients with endometrial cancer. The blood flow analysis showed a significantly lower (P < 0.05) resistance index (RI = 0.37 +/- 0.07) in the cases of endometrial cancer than in patients with benign uterine lesions (0.54 +/- 0.09). Central vessels within endometrial carcinoma tended to have lower velocity and impedance compared to peripheral ones. Significant difference in the impedance of uterine artery blood flow, represented with RI between mentioned groups occurred (P < 0.05). There is a downward trend in the uterine artery RI in patients with endometrial cancer (mean RI = 0.64, ranged from 0.53 to 0.72) regarding benign lesions (mean RI 0.74, ranged from 0.64 to 0.82). PMID- 8365518 TI - Risk-adapted therapy for cancer of the endometrium. PMID- 8365519 TI - Cervical intraepithelial neoplasia: to treat or not to treat! PMID- 8365520 TI - Mechanisms of vascular protection by hormonal replacement therapy. PMID- 8365521 TI - Effects of female sex steroids on breast tissue. PMID- 8365522 TI - Prevention of osteoporosis and reproductive history. PMID- 8365523 TI - Subcutaneous hormone replacement therapy. AB - It is estimated that 75% of women are in an acute estrogen deficiency state within a few years after the onset of the menopause. Every woman inevitably reaches this phase except for a fortunate few who have some source of endogenous estrogens available to them. We believe it would be prudent to offer hormone replacement therapy to every woman with symptoms of the menopause, and to those in whom symptoms are not patently manifest, if an estrogen deficit is present as indicated by vaginal cytology. Certainly even in the absence of symptoms, the presence of osteoporosis is sufficient reason to initiate small doses of estrogens (along with increased calcium and protein uptake, and exercise) for the remainder of the woman's lifetime. Crystalline pellets of 17 beta-estradiol offer excellent relief of symptoms for those postmenopausal women who fare poorly on oral estrogens or intramuscular injections. Although somewhat more expensive than other modes of therapy, pellet use is convenient, highly effective and associated with few side effects. PMID- 8365524 TI - Vaginal progesterone after tubal pregnancy. AB - We studied the effect of vaginal progesterone (P) treatment during the luteal phase of patients who had had a tubal pregnancy (TP) and were planning another, in a prospective, randomized, double-blind trial. The outpatient clinics of two University hospitals and three central hospitals had 135 patients treated for tubal pregnancy: 100 with grossly normal fallopian tubes (supposing an accidentally abnormal luteal phase as a possible etiology of their first TP) and 35 with signs of earlier pelvic inflammatory disease (PID etiology). They were treated with vaginal P (25 mg b.i.d.) or placebo during cycle days 16-24, for 10 months. Serum P levels after a single vaginal or oral dose were compared. The rates of conception, delivery, spontaneous abortion and recurrent TP were recorded, and fetal and placental weight measured. Both vaginal and oral formulas of P provoked a physiological (24-43 nmol/l) rise in serum concentrations. P and placebo-treated cycles resulted in a nearly equal number of pregnancies (33/37 resp.). Of the 55 infants born 53 were to mothers without signs of earlier PID (53/100); only 2 (2/35) to mothers in whom signs had been present. Recurrent TP occurred in 9% of all pregnancies. Four out of six recurrent TPs were patients with signs of PID (4/35), but two were without such signs (2/100): one occurred during placebo and one during P-treated cycle. Prophylactic P treatment of patients at risk of recurrent TP does not improve fertility or prevent recurrent TP. This indicates, that the functional etiology of recurrent TP, as compared to infection, is not important. PMID- 8365525 TI - Conservative treatment for ectopic pregnancy by local application of prostaglandins. PMID- 8365526 TI - Laparoscopic management of tubal ectopic pregnancy. AB - As with laparotomy, laparoscopic treatment of ectopic pregnancy (EP) can be either conservative or radical. After conservative laparoscopic treatment by salpingotomy the risk of failure (between 4 and 6%) is comparable with that observed after similar treatment by laparotomy. The fertility results after laparoscopic treatment of EP are comparable if not better than those observed after similar treatment by laparotomy. These two reasons, together with the considerable advantages of endoscopy over laparotomy, mean that today laparoscopic treatment is without question the best surgical treatment for EP. The prognosis for post-EP fertility is unrelated to the characteristics of the EP (size, rupture, location). The post-EP fertility depends mainly on the patient's previous history. We have established the Therapeutic Scoring System for EP by assessing the different factors affecting future fertility and multivariable analysis. This score allowed us to choose the most suitable treatment to preserve fertility and reduce the risk of recurrence between conservative laparoscopic treatment, laparoscopic salpingectomy with or without contralateral tubal sterilization. PMID- 8365527 TI - Medical treatment of ectopic pregnancy. PMID- 8365528 TI - Expectant management of ectopic pregnancy. PMID- 8365529 TI - What do we know about the origin of CA 125? AB - The murine monoclonal antibody OC 125 recognizes an epitope on a molecule called Cancer Antigen 125 (CA 125). The CA 125 antigen is expressed in amnion and its derivatives of fetal coelomic epithelia (such as Mullerian epithelia, peritoneum, pleura and pericardium) and in many adult tissues (such as the epithelium of fallopian tubes, endometrium, endocervix, pleura and peritoneum). The normal endometrium produces CA 125 and this production can contribute significantly to the level of circulating CA 125 at the time of menstruation. During peritoneal irritation (hyperstimulation, salpingitis, ruptured ectopic pregnancy, laparotomy) peritoneally derived CA 125 significantly contributes to circulating CA 125 concentrations, giving elevated CA 125 values. The use of the CA 125 serum assay as a single diagnostic tool is restricted by the fact that the antigen CA 125 is produced by normal epithelia (of peritoneum, endometrium and benign ovarian cysts) and not only by the ovarian cancer cell. PMID- 8365530 TI - Discordant serum CA 125 values in commercial immunoassays. AB - The CA 125 assay is from a clinical point of view very well suited to monitor ovarian cancer patients. Although most commercial assay systems include as standards CA 125 preparations derived from the OVCA 433 cell line, the various assay configurations do not produce identical results. The so called cut-off value of 35 U/ml obtained in the original Centocor CA 125 assay appears to be equivalent to CA 125 values ranging as low as 18 U/ml and as high as 53 U/ml in other commercial CA 125 assays now available. Because of these dissimilar results, obtained with different immunoassays, switching from one assay to another during follow-up, should not be tolerated. The newly introduced second generation Centocor CA 125 II IRMA was shown to retain the cut-off values of 35 U/ml and 65 U/ml as defined with the original CA 125 IRMA. PMID- 8365531 TI - Rates of cesarean section and perinatal outcome: stillbirths. AB - Based on their yearly clinical statistics for 1983-1989, the cesarean section and stillbirth rates at National Maternity Hospital (Dublin), where the patients are generally white, and University Hospital (Newark), where the patients are predominantly black, were compared. After adjusting for confounding factors, such as unregistered mothers admitted subsequent to fetal demise, differing rates of < 2500 g births and lethal congenital defects, the overall rates of intrauterine fetal demise were identical. When analyzed according to birth weights, in all weight groups, the stillbirth rates were significantly lower in Newark than in Dublin. However, for every 1000 births, more < or = 2500 g fetuses died in utero in Newark than in Dublin. This trend was reversed in the > 2500 g group, where the respective rate at National Maternity Hospital exceeded that of University Hospital more than twice. The latter result largely derived from an almost 7-fold higher rate of intrapartum deaths in the > 2500 g weight group at National Maternity Hospital as compared to University Hospital. When projected against prevailing American statistics, which reflect a stillbirth rate about twice as high among blacks than among whites, the results suggest that the management patterns favored in Newark, including a relatively liberal cesarean section rate (17.5% versus 5.8%), affected the rate of in utero losses favorably. PMID- 8365532 TI - Outcome of 328 pregnancies in 205 women with insulin-dependent diabetes mellitus in the county of Northern Jutland from 1976 to 1990. AB - STUDY OBJECTIVE: To determine the degree of centralization and to describe the outcome of all pregnancies among Type 1 (insulin-dependent) mothers in the county of Northern Jutland from 1976-90. DESIGN: Retrospective, hospital record based study. SETTING: Data were collected from all departments of surgery (n = 8) and obstetrics (n = 3) in the county covering 550,000 inhabitants (approx. 10% of the total Danish population). PATIENTS: Three hundred and twenty-eight consecutive, unselected pregnancies among 205 women with Type 1 diabetes mellitus admitted to the hospitals in the county from 1976-90. MAIN RESULTS: Thirty-two (11%) pregnancies were terminated with spontaneous abortions and ten (3.3%) abortions were induced for medical reasons. There were eleven (4.3%) neonatal deaths. There was no additional fetal loss within the first year of life. Eight (3.1%) babies had major and additionally six (2.4%) minor malformations. Total fetal loss was 53/297 = 18%. Twenty-eight percent of the babies were large-for-gestational age. No pregnancies terminated at primary level hospitals and only 6% at the non-sub specialized obstetrical Departments. CONCLUSION: We have achieved an almost complete centralization of the management of pregnant women with diabetes mellitus and our outcome is comparable to the results published from other regional surveys taking care of these patients. PMID- 8365533 TI - Recurrent eclampsia. Clinical data, morbidity and pathogenic considerations. AB - The analysis of 24 patients with recurrent eclampsia showed that (i) the first attack complicated the second or later pregnancies in nine cases, (ii) there was one or more apparently normal gestations before the second eclampsia in one-third of the patients, (iii) total maternal and neonatal mortality were twice those of general eclampsia, (iv) four autopsies revealed chronic pyelonephritis and cardiac hypertrophy in addition to the characteristic glomerular and hepatic lesions, (v) all six deaths were due to brain damage, and (vi) chronic hypertension was diagnosed in half of the survivors. The results of this study demonstrate that (i) one or several normal pregnancies after eclampsia do not cancel the possibility of another attack, (ii) recurrent eclampsia is an extremely severe event even though most clinical data are no different from general eclampsia, (iii) underlying diseases seem to play a decisive role, and (iv) some aspects of recurrent eclampsia challenge single cause pathogenic mechanisms. PMID- 8365534 TI - Lack of associations between fetal and maternal serum-erythropoietin at birth. AB - Erythropoietin (EPO) is known to be the main regulator of erythropoiesis. We wanted to determine whether EPO production during pregnancy takes place independently in the mother and the fetus, and to identify the factors which set the EPO level. Endogenous EPO levels were determined in simultaneous samples from the umbilical vein, the umbilical artery and a maternal vein in 126 mother-child pairs and simultaneously from amniotic fluid (n = 14) in unselected births. Results were related to clinical and biochemical parameters of fetal well-being, mode of delivery, duration of labor, and infant parameters at birth. There was a weak correlation between maternal and fetal log EPO values (umbilical vein: r2 = 0.11; umbilical artery: r2 = 0.08), but a highly significant correlation between log EPO levels in the two umbilical vessels (r2 = 0.91) and between both umbilical blood and amniotic fluid (r2 = 0.41). Maternal EPO levels were lower than fetal levels in 76 cases, higher in 47, and nearly identical in 3. Increased fetal EPO levels were associated with clinical and biochemical indicators of fetal stress. These associations help to explain why EPO concentrations in fetal blood are independent of maternal levels and also indicate that EPO does not cross the placental barrier. These findings are discussed in the light of the animal experimental and in vitro evidence for placental transfer of EPO. Our data, and the work of others, make such a transfer in humans quite unlikely. This observation has therapeutical consequences for the treatment of maternal anemia with recombinant human EPO. PMID- 8365535 TI - European multicentre studies in the field of obstetrics. AB - Within Europe a number of multinational, multicentre studies are performed in the field of Obstetrics and Gynaecology. Many of these are funded by the European Community. Unfortunately, concise information on currently ongoing European multicentre studies is not easily obtainable. There is no particular central information point. The current overview aims to provide insight in obstetrical EC/European multicentre studies which recently have been finished, are ongoing or have been planned for the near future. The various projects are described, and information on the number of participants, the research period, the responsible project leader and framework of each project is summarized in tables. A list with the addresses of the project leaders and/or contact persons in the EC member states is added. The paper hopes to facilitate researchers and institutes involved in Obstetrics within Europe to make easier contacts and to promote collaboration on the international level. PMID- 8365537 TI - Influence of audit and feedback on use of caesarean section in a geographically defined population. AB - The influence of audit and feedback on use of caesarean section was investigated in a geographically defined population. At the beginning of 1986 and throughout that year the three principal reasons for the increased use of caesarean section were drawn to the attention of the resident obstetricians in the hospital where 85% of the women resident in the health district gave birth. A repeat survey of the indications for caesarean section was conducted for 1986 births. Despite an increase in the number of women delivered in 1986 who had previously had two or more sections, the caesarean section rate fell from 15.9% in 1982 to 12.7% in 1986 (P < 0.005). Most of this decrease was due to a reduction in caesarean section for the three indications that were the main contributors to the increased rate between 1974 and 1982. The rate for the women who gave birth in the hospital whose resident obstetricians had been informed about the preceding audit was 12.2%, compared with 15.6%, for the women who gave birth in other hospitals. Audit and feedback of specific information, imparted in a non directive way to resident obstetricians responsible for performing caesarean section, probably accounted for a more rational use of caesarean section. PMID- 8365536 TI - Immune response to hepatitis B vaccine in pregnant women receiving post-exposure prophylaxis. AB - Hepatitis B immunoglobulin and vaccine were given as post-exposure prophylaxis to 73 women after an outbreak of hepatitis B due to in vitro fertilization treatment. The immunization schedule consisted of 5 ml of hepatitis B immunoglobulin (125 IU/ml) at months 0 and 1 and recombinant hepatitis B vaccine (10 micrograms of HBvaxDNA) at months 0, 1, 2 and 6. The safety and immunogenicity of hepatitis B vaccine were studied in 16 women who became pregnant after in vitro fertilization; 57 non-pregnant women receiving the same treatment served as controls. Blood samples were drawn at 0, 1, 2, 6 and 7 months. One patient had a clinical abortion 2 days after initial immunization; other side effects of vaccination were not found in vaccinees or in their offspring. All vaccinees exhibited antibodies against hepatitis B surface antigen after vaccination but relatively low peak geometric mean titers of 258 IU/l and 684 IU/l were attained in pregnant and non-pregnant women, respectively. There were no significant differences in seroconversion rates and geometric mean titers between the two groups although the immune response to hepatitis B vaccine was slower and lower in pregnant women at all times. Our results suggest that when post-exposure prophylaxis for hepatitis B infection is indicated, passive active immunization can be started safely during pregnancy. The relative weak response to the vaccine calls for monitoring of the anti-HBs 1 month after the initial series of vaccinations. PMID- 8365538 TI - Perinatal mortality in Greece and Greek-born women in Victoria. What does a 'natural experiment' suggest? AB - A comparison of perinatal outcome in the Greek perinatal mortality survey of 1983 with the outcome of births to Greek born women who had migrated to Victoria, Australia found marked similarities in maternal age, parity, marital status and cigarette smoking. The birthweight distributions were almost identical in the two groups. Despite these similarities the perinatal mortality was substantially higher in Greece. Analysis by cause of death showed the differences to be marginal in all categories except deaths attributed to intrapartum asphyxia which were eight times as common in Greece. PMID- 8365539 TI - Five-year follow up of patients with cervical intra-epithelial neoplasia in the cone margins after conization. AB - Three hundred eighty-five women treated with conization due to repeated CIN I, CIN II or CIN III of the cervix uteri have been followed up for 5 years. All cones were classified according to diagnosis and status of the resection margins. A significantly greater recurrence rate of 16.2% was found in the group with neoplasia in the resection margins, in contrast to 3.9% in the group with normal resection margins. However, 83.8% (75.4-92.2%) of patients with neoplasia in the resection margins can be expected to be free of recurrence after a 5-year postoperative follow-up period. Whether the non-free resection margins were endocervical, ectocervical or both, did not influence the recurrence rate. While the prevalence of non-free resection margins increased significantly with increasing dysplasia, this could not be found with increasing age. The risk of recurrence could not be correlated with the grade of dysplasia. We conclude that neoplasia in the resection margins of the cone represents an increased risk of recurrence. Therefore, we changed the normal smear check-up with a cotton-swab to smear with cyto-brush, supplemented with colposcopy in the non-free resection margin group, but it remains to be proven that this procedure is safer. PMID- 8365540 TI - Current management of ruptured corpus luteum. AB - The objectives of the study are to assess current management of the rather frequent event of ruptured corpus luteum. Special emphasis is made on the value of ultrasonography, laparoscopy and culdocentesis in deciding appropriate treatment. A series of 70 patients with ruptured corpus luteum diagnosed and treated during a period of 6 years in one institution in Israel is reported. Eighteen patients with concurrent ruptured corpus luteum and ectopic pregnancy are included. Abdominal pain, the most prevalent presenting symptom, has no typical characteristics. The correlation between large amount of fluid as observed by ultrasound and the finding of > 250 ml of blood at laparotomy is very high. Culdocentesis was performed in only 21 patients. Surgical intervention (laparoscopy, laparotomy following laparoscopy or direct laparotomy) was carried out in 58 patients (83%). The remaining 12 cases were handled by observation only. Forty patients required laparotomy in whom 17 underwent wedge resection. We conclude that observation is sufficient treatment in hemodynamically stable patients, without severe abdominal pain and in the presence of a small amount of pelvic fluid demonstrated by ultrasound. When a large amount of fluid is observed and/or in the presence of severe abdominal pain laparoscopy should be performed on admission. Direct laparotomy is mandatory in case of circulatory collapse. PMID- 8365542 TI - Interaction of serum albumin with the Fe(III)-citrate complex. AB - 1. Fe(III)-citrate forms a red coloured complex with bovine serum albumin (lambda max = 500 nm). 2. Fe(III)-albumin complexes also appear, when Fe(III)-citrate is mixed with albumin, suggesting that albumin competes with citrate for ferric ions. PMID- 8365541 TI - Localization of steroid hormone receptors in the pelvic muscles. AB - After the menopause the pelvic floor becomes progressively weaker, one consequence of which is the increasing incidence of prolapse and urinary incontinence. It is plausible that the reduction in estrogen levels postmenopausally is an etiological factor in these problems. For the pelvic floor muscles to be considered as target organs for estrogen, demonstration of the presence of estrogen receptors is required. The present study aims to confirm previous findings of estrogen and progesterone receptors in the levator ani muscle, and to further localize them histologically. In seven women biopsies from the levator ani muscle were taken and analyzed immunohistologically with monoclonal antibodies for estrogen and progesterone receptors. The receptors were detected in the nuclei of connective tissue cells and striated muscle cells. These findings provide a scientific basis for a possible beneficial effect of estrogen therapy, as a complement to other therapies, in prolapse and urinary incontinence. PMID- 8365544 TI - Effects of Mg2+ and Ca2+ on Fe2+ uptake by Bifidobacterium thermophilum. AB - Ferrous iron uptake was investigated in Bifidobacterium thermophilum (B. thermophilum) in the presence of Mg2+ and Ca2+ with the following findings: 1. Mg2+ inhibited Fe2+ accumulation in the cells in a dose-dependent manner at 37 degrees, but not at 0 degrees. Removal of Mg2+ from the medium resulted in a resumption of rapid iron uptake. 2. Mg2+ had no effect on the binding of Fe2+ by B. thermophilum protoplasts, its cellular particulate fraction, or distribution between the particulate and soluble fractions. 3. Ca2+ exerted a stimulatory effect on iron uptake by B. thermophilum, but was not able to reverse the inhibitory effects of Mg2+. 4. It was concluded that Mg2+ has no effect on the binding of iron on the surface or interior of B. thermophilum and that it affected the Fe2+ transport mechanism (permease) in a reversible manner. It is possible that iron and magnesium share the same permease in this microorganism. PMID- 8365543 TI - Identification of annexin II, annexin VI and glyceraldehyde-3-phosphate dehydrogenase as calcyclin-binding proteins in bovine heart. AB - 1. Matrix-immobilized calcyclin as affinity ligand in chromatography led to purification of three protein bands at 68, 36 and 35 kDa from bovine heart that required Ca2+ for binding. 2. Polyacrylamide-immobilized phosphatidylserine separated this fraction into a phospholipid-binding part (68 kDa, 35 kDa), also attaching to phospholipid vesicles even in the presence of calcyclin, and a flow through part, constituting approx 30% of the total fraction (36 kDa). 3. Enzyme assays and electrophoretic mobility showed an at least close relationship of the 36 kDa band to glyceraldehyde-3-phosphate dehydrogenase. Interaction between enzyme and calcyclin in a solid-phase assay was inhibited by sialoglycoproteins and depended strongly on the integrity of carboxyl and hydrophobic groups of the enzyme. The interaction between the two proteins had a KD value of 110 nM. 4. Application of annexin-specific antibodies revealed an immunological relationship of the 35 and 68 kDa calcyclin-binding proteins to members of the annexin family, namely to annexin II (35 kDa) and annexin VI (68 kDa). The N-terminal amino acid sequence of a cleavage peptide of the 68 kDa protein was identical to a sequence stretch in human annexin VI, corroborating this evidence. PMID- 8365545 TI - In vitro phosphorylation of proteins tightly bound to DNA by protein kinase NII. AB - 1. Highly purified DNA from calf thymus was phosphorylated with protein kinase NII. 2. Digestion with proteinase K of this DNA demonstrates proteins as phosphorylated component. 3. Gel filtration chromatography on Bio-Gel A-0.5m gel column shows a major protein peak between 50 and 70 kDa. 4. SDS gel electrophoresis, after hydrolysis, to digest completely DNA, shows three major phosphorylated bands corresponding to polypeptides of M(r) between 31 and 21 kDa. 5. After high voltage electrophoresis on TLC plates tryptic digested polypeptides show very similar phosphopeptides patterns. PMID- 8365546 TI - Thyroxine type II 5'-deiodinase activity in pineal and Harderian gland is enhanced by hypothyroidism but is independent of serum thyroxine concentrations during hyperthyroidism. AB - 1. This paper studies the effect of thyroid status on 5'-D activity in pineal gland, Harderian gland, brown adipose tissue (BAT), pituitary gland, brain frontal cortex (BFC), and cerebellum. 2. Hypothyroidism clearly increased diurnal 5'-D activity in Harderian gland, BAT, pituitary gland, BFC, and cerebellum. In pineal gland, diurnal values of 5'-D activity were not affected by hypothyroidism. 3. Hypothyroidism in adult rats clearly enhanced nocturnal increase of 5'-D activity in pineal and Harderian gland. Congenital hypothyroidism also enhanced the nocturnal increase of 5'-D activity in pineal gland. 4. Hyperthyroidism inhibited 5'-D activity in pituitary gland, BFC, and cerebellum. A small inhibition, although significant, was found in BAT. 5. In pineal and Harderian gland, hyperthyroidism did not inhibit either the basal diurnal values of the enzyme or the nocturnal increase of its activity. 6. Results suggest that, in tissues where 5'D-activity is regulated by adrenergic mechanisms, mostly pineal gland and Harderian gland, the enzyme activity is independent of serum T4 concentrations during hyperthyroidism. PMID- 8365547 TI - Characterization of the ferredoxin gene transcripts in bovine liver and brain. AB - 1. To study the expression of a ferredoxin gene in extra-adrenocortical tissues, the amounts and structures of the ferredoxin gene transcripts in bovine liver and brain were studied and compared to those of that in adrenocortex. 2. The sizes and amounts of the ferredoxin mRNAs were analyzed by means of Northern blotting, RNA slot blotting and RT-PCR. 3. The nucleotide sequences were determined for 39 ferredoxin cDNA clones from bovine liver. 4. The results indicated that the sizes of the ferredoxin mRNAs in liver and brain were the same as that in adrenocortex, however, their amounts were approx 1/30th and less than the latter, respectively. 5. Although the multiple forms of ferredoxin cDNA, differing in the poly(A) addition sites, were also found in liver, a minor form of ferredoxin cDNA, produced through alternative promoter usage and splicing, could not be detected in liver. 6. The nucleotide sequences of all hepato-ferredoxin cDNA clones obtained were identical to that of a major type of adreno-ferredoxin. 7. These results showed that the expression level of the ferredoxin gene in different tissues was controlled by the amount of mRNA. PMID- 8365548 TI - Glycolytic enzymes as DNA binding proteins. AB - 1. Numerous studies have demonstrated the presence of at least four glycolytic enzymes in the nuclear compartment of several cell systems. 2. These include, lactate dehydrogenase, phosphoglycerate kinase, aldolase and glyceraldehyde-3 phosphate dehydrogenase. 3. In some cases the glycolytic enzymes found in the nuclei were a modified form from that found in the cytoplasmic counterpart. 4. In all four cases, the nuclear form of these glycolytic enzymes has been reported to bind DNA. 5. Although none of these enzymes interact with a specific target DNA sequence, their association with DNA may play a role in transcription and replication of DNA through general stabilization of the nuclear matrix or chromatin structure. 6. The present review aims to summarize the current understanding of this phenomenon and to examine the role of the DNA-binding activities of the glycolytic enzymes in cell growth and differentiation. PMID- 8365549 TI - Post-translational chemical modifications of proteins--III. Current developments in analytical procedures of identification and quantitation of post-translational chemically modified amino acid(s) and its derivatives. AB - 1. The Chemical modifications of amino acids and their derivatives are mainly due to different post-translational enzymatic reactions. 2. The enzymatic reactions resulting in amino acids such as acetylation-, formylation, methylation phosphorylation-, sulfation-, hydroxylation, ADP ribosylation-, carboxylation-, amidation-, adenylylation-, glycosylation-, ubiquitination-, prenylation and acylation are listed and analytical methods are reported and extensively reviewed. 3. The post-translationally modified cross-linking molecules after maturations such as desmosines, allo-desmosine, hydroxy-, lysylpyridinoline, 3 hydroxypyridinium derivatives, cyclopentenosine recently found in matured elastin, and in collagen, and pulcherosine a novel tyrosine-derived found in fertilization envelope of Sea Urchin embryo, di-tyrosine in resilin, gamma glutamyl-lysine isopeptide cross-linking molecule etc. are listed and both physico-chemical and analytical methods are extensively reviewed and discussed. 4. Other consequences of post-translational modifications encountered in the analytical procedure such as N-terminal step-wise Edman degradation of glycosylated site(s), phosphorylated-site(s) and or sulfated-site(s) were also reported by us. PMID- 8365550 TI - Spectrofluorometric studies of nile red treated native and oxidized low density lipoprotein. AB - 1. The excitation and emission maxima of nile red in the presence of LDL were found to be 526 and 587 nm, respectively. Oxidation of LDL for 16 hr in the presence of CuSO4 resulted in significant spectral shifts to longer wavelengths in both the excitation and emission spectra. 2. The difference in the fluorescence intensity between native and oxidized LDL was most pronounced at wavelengths between 550 and 580 nm. At these emission wavelengths, the relative fluorescence intensity of nile red treated oxidized LDL was found to be decreased by approx 30% when compared to that observed in the presence of native LDL. 3. Differences in the nile red fluorescence spectra were not observed when LDL and acetylated LDL were compared. PMID- 8365551 TI - Uncoupling of mitochondrial oxidative phosphorylation abolishes the stimulatory action of insulin on the binding of glycolytic enzymes to muscle cytoskeleton. AB - 1. We show here that treatment of diaphragm muscle with 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, abolished the stimulatory action of insulin on binding of the glycolytic enzymes, phosphofructokinase (PFK) and aldolase, to muscle cytoskeleton. This effect was demonstrated with low concentration of DNP, which caused only a small decrease in ATP and did not affect the basic levels of cytoskeleton-bound glycolytic enzymes. 2. Higher concentrations of DNP, which induced a drastic decline in ATP content, caused a decrease in cytoskeleton-bound glycolytic enzymes and damage to myofibrils. 3. These results suggest that mitochondrial ATP is required for both the preservation of the basal levels of cytoskeleton-bound glycolytic enzymes and cell structure, as well as for the expression of the stimulatory action of insulin on glycolytic enzymes' binding to muscle cytoskeleton. PMID- 8365552 TI - Characterization of calcyclin fragments obtained by CNBr-cleavage. AB - 1. Two calcyclin fragments were obtained by CNBr-cleavage. 2. One fragment represented N-terminal end of a molecule (residues 1-56), and another one a C terminal end (residues 57-89). 3. Properties of intact calcyclin such as binding of calcium, binding to hydrophobic resins and interaction with calcyclin specific antibodies were not retained by these fragments. 4. However, both fragments were able to form dimers and higher forms of aggregates as seen for uncleaved calcyclin. 5. This indicates that both halves of the molecule contain the regions responsible for non-covalent interaction which might participate in dimer formation. PMID- 8365553 TI - Origins of neural crest cell diversity. AB - The neural crest is a population of migratory cells, arising from the ectoderm, that invades many sites within the embryo and differentiate into a variety of diverse cell types. Pigment cells, most cells of the peripheral nervous system, adrenal medullary cells, and some cranial cartilage are derived from the neural crest. Despite a wealth of knowledge concerning their pathways of migration and vast array of derivatives, little is known about the formation of neural crest cells or their acquisition of positional identity. This review focuses on the origin of neural crest cells from the ectoderm and the generation of differences in neural crest cell fates along the rostrocaudal axis. In addition, we consider the role of temporal restriction in the developmental potential of premigratory neural crest cells. While evidence for the existence of multipotent stem cells is strong, some experiments also suggest that there may be heterogeneity among neural crest cell precursors, perhaps due to differences in origin, that might explain commitment events occurring early in neural crest development. PMID- 8365554 TI - Developing rat retinal ganglion cells express the functional NGF receptor p140trkA. AB - The expression and cellular localization of NGF receptors in the developing rat retina were investigated immunocytochemically and biochemically. In in vitro preparations of retinal neurons from neonatal rats the functional NGF receptor p140trkA was immunocytochemically detected on retrogradely labeled retinal ganglion cells (RGCs). In transverse retinal sections p140trk-immunopositive cells were localized exclusively at the level of the RGC layer. Affinity labeling with 125I-NGF, chemical cross-linking, and immunoprecipitation with anti-NGF antibodies revealed the presence of three complexes which migrate on SDS-PAGE at approximately 90, 95, and 150 kDa. The bands at 90 and 95 kDa correspond to the so-called low affinity NGF receptor p75NGFR. Western blotting experiments using anti-TRK antibodies revealed that the slowest migrating band (150 kDa), which is not immunoprecipitated by monoclonal antibodies to p75NGFR, corresponds to p140trkA. The presence of the functional NGF receptor on RGCs provides the molecular explanation for the reported sensitivity of these cells to the biological action of NGF. PMID- 8365555 TI - Lineage diversification of the neural crest: in vitro investigations. AB - This review addresses the contribution of in vitro investigations to our understanding of neural crest development. Cell culture has been used to study the environmental control of cell lineage decisions in the neural crest and to define the developmental potentials of specific populations of neural crest and neural crest-derived cells. We consider the roles of environmental signals in the context of the development of several different neural crest-derived lineages. We also discuss evidence for influences of local cell-cell interactions and substrate molecules on neural crest development. Data bearing on the issues of neural crest cell multipotency, self-renewal, and lineage commitment are reviewed. PMID- 8365556 TI - Sperm, inositol trisphosphate, and thimerosal-induced intracellular Ca2+ elevations in rabbit eggs. AB - Fertilization-induced calcium (Ca2+) changes were examined in in vivo fertilized rabbit eggs, using the fluorescent Ca2+ inducer fura-2 dextran. Twenty-four of 48 fertilized eggs exhibited repetitive Ca2+ rises with intervals of 13 +/- 1 min (mean +/- SEM) during the recording period of 45 min. None of the unfertilized eggs showed Ca2+ rises (6/6). The mean peak Ca2+ concentration ([Ca2+]i) was 466 +/- 30 nM and the average duration was 100 +/- 3 sec. The amplitude of the Ca2+ rises decreased and the duration increased as the stage of fertilization progressed from recently fertilized to pronuclear apposition (P < 0.05). In unfertilized eggs, Ca2+ release was elicited by injection of inositol 1,4,5 trisphosphate (InsP3; 5 microM in the injection pipette) with a mean peak [Ca2+]i of 764 +/- 88 nM and a duration of 28 +/- 1 sec (n = 9). Injection of InsP3S3 (500 microM), a nonmetabolizable analogue of InsP3, induced repetitive Ca2+ rises different from sperm-induced rises in periodicity and duration. Exposure to 400 microM thimerosal caused spontaneous Ca2+ rises (1.4 +/- 0.1 Ca2+ rises in 45 min of measurements) with an amplitude of 1200 +/- 54 nM and duration of 114 +/- 8 sec. Heparin injection (100 mg/ml), an InsP3 receptor antagonist, blocked both InsP3 and thimerosal-induced spontaneous Ca2+ rises. Successive application of InsP3 and thimerosal in Ca(2+)-free medium showed that either InsP3 or thimerosal produced smaller Ca2+ rise(s) when preceded by Ca2+ rise(s) induced by the other agonist. The results of this study indicate that rabbit eggs, like other mammalian eggs, exhibit repetitive Ca2+ rises during fertilization. InsP3 and thimerosal stimulate intracellular Ca2+ release most likely from a common large intracellular pool by activating the InsP3 receptor. PMID- 8365557 TI - Isolation and characterization of Xenopus follistatin and activins. AB - Xenopus follistatin and activins were purified from a Xenopus laevis cell line (XTC-F1) by four purification steps consisting of consecutive affinity chromatography on dextran sulfate-Sepharose and Sulfate Cellulofine, fast protein liquid chromatography gel permeation, and reverse-phase high performance liquid chromatography (HPLC). Our results thus obtained indicated that almost equimolar amounts of activins A, AB, and B were found to be present as a complex with follistatin (activin-binding protein) in the conditioned medium of XTC-F1 cells. Reverse-phase HPLC of the complex gave Xenopus follistatin and activins A, AB, and B. The purified Xenopus follistatin showed four major bands in a molecular mass range from 34 to 39 kDa by SDS-polyacrylamide gel electrophoresis under nonreducing conditions. The ability of each form of the protein to specifically bind activin was determined by activin-binding assay and ligand blotting analysis. Each protein was found to have the same NH2-terminus and its sequence was very homologous to that of mammalian follistatin. Several criteria including immunoblotting analysis and various functional assays revealed the existence of three isoforms of activins A, AB, and B in Xenopus, as in mammals. Xenopus activins significantly induced both ventral and dorsal mesoderm in explants of Xenopus blastula cells that would otherwise form epidermis. In a dose-dependent manner of each isoform of activin, the induced explants were able to differentiate into blood-like cells, coelomic epithelium, mesenchyme, muscle, and notochord. The induction patterns of three Xenopus activins were essentially the same. The mesoderm induction by the purified Xenopus activins was shown to be inhibited stoichiometrically by the purified Xenopus follistatin. These results indicate that Xenopus XTC-F1 cells secrete several molecular forms of follistatin/activin-binding protein and three isoforms of activins AB and B in addition to activin A. PMID- 8365558 TI - Germline stem cell division and egg chamber development in transplanted Drosophila germaria. AB - Germline and somatic stem cells reside within the anterior region (or "germarium") of each ovariole in the Drosophila ovary. When individual germaria were dissected free of developing eggs and sheath tissue and transplanted into the abdominal cavity of a host fly, they regenerated ovariole-like structures and continuously supported the entire process of oogenesis, indicating that the stem cells remained functional. This system allowed us to measure the duration of several stages in oogenesis and to analyze the role of specific germarial cells in providing stem cell function. Laser ablation of presumptive germline stem cells near the apical tip prior to transplantation blocked the production of new germline cysts, but allowed previously initiated cysts to complete development. This confirmed the location of germline stem cells and showed that subsequent development of preexisting cysts did not require continued cyst production. Ablation of a distinct group of somatic cells lying close to the germline stem cells ("the terminal filament") increased the rate of oogenesis by approximately 40%, suggesting that the terminal filament may negatively regulate stem cell division. PMID- 8365559 TI - Nerve-dependent and -independent patterns of mRNA expression in regenerating skeletal muscle. AB - Muscle regeneration was used to assess the roles of innervation and intrinsic genetic information in the acquisition of predominant slow and fast contractile protein mRNA profiles in adult skeletal muscle. Rat soleus (slow) and EDL (fast) muscles were allowed to regenerate in the presence and absence of their respective slow and fast nerves. Levels of mRNAs encoding fast, slow, and cardiac contractile protein isoforms were quantitatively determined at specific times during regeneration. All muscles initially expressed a heterogeneous pattern of fast, slow, and cardiac isoform mRNAs during myotube formation. Subsequently, the EDL muscle made a transition to a predominantly fast profile of mRNAs which was independent of innervation. The mRNA profile for the noninnervated regenerating soleus muscle was similar to both the innervated and the noninnervated EDL muscle profile. Thus, the decision to express predominantly fast isoform mRNAs is intrinsic to in vivo muscle regeneration with the fast nerve not appearing to be informative. In contrast, acquisition of a slow mRNA profile is dependent on the presence of a slow nerve. The mRNAs encoding slow isoforms from all of the contractile protein gene families are upregulated during the period of reestablishment of neuromuscular transmission. Additionally, there is no concomitant down-regulation of the fast isoform mRNAs upon reinnervation in the soleus regenerate. We propose that information both intrinsic to the muscle and supplied by the in vivo environment acts to provide potential isoform mRNA options to the regenerating muscle. PMID- 8365560 TI - Lineage analysis of early neural plate cells: cells with purely neuronal fate coexist with bipotential neuroglial progenitors. AB - To investigate the lineage relationships of neurons and astroglial cells early in central nervous system development, we have analyzed the progeny of neural plate cells in an amphibian embryo (Pleurodeles waltl). A fluorescent tracer, lysinated rhodamine-dextran, was iontophoretically injected into individual precursor cells in various areas of the early neural plate. The phenotypes of clonally related cells were identified in the hindbrain and spinal cord by morphological and immunohistochemical criteria 12 days later, at larval stages. We found that the large majority of clones (83%) contained both neurons and astroglial cells, whereas the remainder (17%) were homogeneous and were only composed of neurons. We never observed purely astroglial clones. These results clearly demonstrate the predominance of bipotential progenitors in the neural plate. Interestingly, the progenitors with a restricted neuronal fate were always located along the intermediate axes of the neural plate, while mixed progenitors were found in all areas examined. The analysis of migratory paths has shown that sister cells first migrated together along radial pathways without dispersion along the rostrocaudal axis. From larval stages, some neurons migrated away from the original clonal cohort along dorsoventral and ventrodorsal tangential routes, but only after they had reached the border between the intermediate and marginal zones. PMID- 8365561 TI - Inhibition of differentiation in P19 embryonal carcinoma cells by the expression of vectors encoding truncated or antisense EGF receptor. AB - Murine embryonal carcinoma cells do not express detectable cell-surface epidermal growth factor receptors (EGF-R) but after 2 days of differentiation induced by retinoic acid (RA) increasingly express mRNA and protein encoded by the EGF receptor gene (Joh et al., Cell Growth and Differentiation 3, 315, 1992). The effect on morphology, growth, and differentiation of the introduction of expression vectors that produce either a truncated, kinase-negative mouse EGF receptor or an antisense mRNA was studied in P19 embryonal carcinoma (EC) cells before and after differentiation. The presence of either construct should lead to the reduction of EGF-R expression by either the dominant negative effects of a truncated protein or the inhibition of endogenous EGF-R mRNA production/translation by complementary RNA, respectively. Cells were cotransfected with the bacterial neomycin resistance gene and constitutively expressing clones were selected with G418. The cytomegalovirus LTR promoter/enhancer was found to be very inefficiently activated in P19 EC cells. After RA addition, changes in gene expression included induction of both the exogenous truncated constructs and endogenous EGF-R. Differentiation was gauged by the expression of tissue-type plasminogen activator and intermediate filament protein markers of neural tissues, as well as EGF-R. The expression of 120-kDa truncated EGF-Rs was high in four clones, but all 10 clones examined had diminished abilities to differentiate after RA induction compared to four control cell lines. Similarly, the majority of antisense transfected clones was unable to differentiate normally. The results indicate that the reduced expression of EGF Rs in differentiating EC cells inhibits the rate, frequency, and extent of differentiation after RA induction. We conclude that the expression of EGF-Rs plays a role in the stimulation of differentiation and we speculate that the mechanism involves the tyrosine kinase activity of the receptor. PMID- 8365562 TI - Basic FGF maintains some characteristics of the progress zone of chick limb bud in cell culture. AB - The apical region of chick limb buds (progress zone, PZ) is known to be essential for limb pattern formation. In the PZ, the cells are in an uncommitted state and change their positional values under the influence of the apical ectodermal ridge (AER). Using a culture system of chick PZ cells, we have examined the factor(s) which helps to maintain some of the characteristics of PZ cells. It was found that basic FGF (bFGF) stimulated the expression of AV-1 and Msx 1 mRNA, which are rich in PZ cells at early stages, in the cultured PZ cells. These two molecules were rapidly lost in the control culture without the bFGF. Further, bFGF promoted growth and inhibited chondrogenesis of the cultured PZ cells. When quail PZ cells were cultured in FGF medium, harvested, and grafted to the apical region of chick limb buds, in about half of the grafts, the cells distributed to form a long band along the proximodistal axis and participated in normal host cartilage pattern formation as did intact PZ tissues. In contrast, those cultured in the medium without bFGF distributed as a cluster and did not participate in host cartilage pattern formation. The culture with conditioned medium of BRL cells increased the percentage of the grafts participating in normal pattern formation. These results indicate that bFGF helps to maintain some of the characteristics of PZ cells in culture and suggest that bFGF may be a PZ maintenance factor from the AER. PMID- 8365563 TI - Patterning of neural crest derivatives in the avian embryo: in vivo and in vitro studies. AB - In this article we review recent findings from our laboratory on the developmental fate of the neural crest as studied in the avian embryo using the quail-chick marker system in vivo. Quail-chick chimeric experiments carried out at the late neurula stage have revealed the contribution of the neural crest to the skull vault, i.e., the frontal and parietal bones, previously thought to be mesodermally derived. At early developmental stages, the fate of the cephalic mesoderm (free of neural crest cells) could be analyzed. The striking result was that the mesoderm does not contribute to the head and face dermis except in the occipital and otic areas where the skull is derived from the cephalic and somitic mesoderm. Thus, the neural crest forms the dermis, the membrane and cartilage bones of the skull vault, the skull basis, and the face. The limit of the mesoderm-derived skeleton in the skull basis is located in the sella turcica between the basipre- and the basipostsphenoid and coincides with the tip of the notochord. We thus define a "chordal" and an "achordal" skull, the latter being all derived from the neural crest. These results are discussed in the framework of the "New Head" concept of Gans and Northcutt (1983). The second part of this review deals with the role of the environment in the morphogenesis and diversification of neural crest derivatives. The role of the rostrocaudal heterogeneity of the somites in establishing the metameric pattern of the truncal neural crest derivatives is analyzed. The respective contributions of the "in embryo" and in vitro approaches to our understanding of the neural crest cell differentiating potentialities are reviewed. It is pointed out that the search for survival and proliferation factors acting locally on neural crest derivatives when they are wandering and/or settling in various embryonic locations constitutes the new challenge for further understanding their complex patterning and the highly diversified variety of their phenotypes. PMID- 8365564 TI - Brain-derived neurotrophic factor and neurotrophin-3 induce cell proliferation in the cochleovestibular ganglion through a glycosyl-phosphatidylinositol signaling system. AB - We have investigated the role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the regulation of cell proliferation in the early developing cochleovestibular ganglion (CVG). Ganglia were isolated from 72-hr chick embryos and cultured for 24 hr. Both BDNF and NT-3 had a powerful mitogenic effect, at doses of 1-5 ng/ml, consistent with an involvement of the high affinity receptor. Evidence for the participation of the glycosyl phosphatidylinositol (GPI)/inositol phosphoglycan (IPG) signaling system in the mediation of proliferative effects of BDNF and NT-3 is presented. Both of these neurotrophins elicited a fast and transient hydrolysis of labeled GPI, approximately 60% in 30 sec. The dose-response profile of GPI hydrolysis overlaps the neurotrophin-induced cell proliferation response profile. Anti-IPG antibodies were able to block the growth-promoting effects of BDNF and NT-3. Anti-IPG antibodies immunoprecipitated a CVG-endogenous IPG, induced upon BDNF treatment, which exhibited proliferative stimulating properties. Both BDNF and NT-3 are proposed as potential candidates for regulation of growth during CVG development, with this mitogenic effect being mediated by the GPI/IPG signaling system. PMID- 8365565 TI - Brain-derived neurotrophic factor and neurotrophin-3 support the survival and neuritogenesis response of developing cochleovestibular ganglion neurons. AB - The effects of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the differentiation of avian cochleovestibular ganglion and their possible association with the hydrolysis of glycosyl-phosphatidylinositol (GPI) were studied. BDNF and NT-3 (2 ng/ml) promoted neurite outgrowth in explants of both cochlear and vestibular ganglia. This effect on neuritogenesis was stage dependent, reaching a maximum at E7 for NT-3 and at E9 for BDNF. The magnitude of the response of the vestibular ganglion to BDNF was always smaller than that of the cochlear ganglion of an equivalent stage. BDNF and NT-3 stimulation of neuronal survival and neurite extension was also demonstrated in dissociated neuronal cell cultures. The effect was concentration-dependent with saturation of the response occurring at 4 ng/ml for BDNF and at 2 ng/ml for NT-3, the half maximal effect occurring at 2 and 1 ng/ml, respectively, for the most sensitive stages of the chick cochlear ganglion. Inositol phosphoglycan (IPG) did not mimic the effects of BDNF or NT-3 on neuronal survival and neurite outgrowth, nor was it able to potentiate their responses. Antibodies raised against IPG did not block the effects of these neurotrophins. The results suggest that BDNF and NT-3 may act in cooperation to establish the innervation pattern of the inner ear. Unlike their early proliferative effects, neurotrophic effects are uncoupled from the GPI/IPG signal transduction system. PMID- 8365566 TI - Identification of two regions from the Drosophila decapentaplegic gene required for embryonic midgut development and larval viability. AB - The Drosophila decapentaplegic (dpp) gene, a member of the transforming growth factor-beta family, is required for dorsal/ventral pattern formation and midgut and imaginal disk development. We have identified a 3-kb upstream regulatory region necessary for dpp expression in the visceral mesoderm of the gastric caeca primordia and a second 2.5-kb upstream regulatory region necessary for dpp expression in the midgut visceral mesoderm corresponding to a portion of abdominal segments 1 and 2 (parasegment 7). These regulatory regions act over a distance of up to 10-kb on all four of the dpp promoters examined. Absence of dpp expression in the gastric caeca primordia caused defective development of the gastric caeca and a concomitant partial reduction in larval and pupal viability. Absence of dpp expression in the visceral mesoderm of parasegment 7 caused a reduction in the length of the central portion of the larval gut and a change in the morphology of the midgut cells in this region but had little effect on the survival of the animals to the adult stage. However, a larval lethal phenotype was observed when both the central portion of the larval midgut and the gastric caeca were defective. PMID- 8365567 TI - DNA replication in fertilized eggs of the starfish Asterina pectinifera. AB - Early starfish embryos were labeled with 5-bromo-2'-deoxyuridine (BrdU; the thymidine analogue) for 3-4 min of pulse, and the BrdU incorporated into newly replicated DNA was immunocytochemically detected with anti-BrdU antibody. Series of optical sections of the stained embryos observed with a confocal laser scanning microscope (CLSM) were collected, and three-dimensional images of the chromatin and the incorporated BrdU were reconstructed on a computer display. The distribution of the DNA replication sites and the chromatin structure were investigated from a three-dimensional point of view. The oocytes fertilized during maturation and the eggs fertilized after maturation were examined for the timing of S phase, DNA replication pattern, and chromatin distribution in the nucleus. Duration of the first S phase between the two types of embryos differed in the first S phase, but was the same in the second and third S phases. We observed a successive change in the distribution of DNA replication sites from a "uniform" to a "condensing" pattern during a single S phase traverse, except in the first S phase of the eggs fertilized after maturation. These two patterns of DNA replication almost coincided with chromatin visualized by anti-single stranded DNA antiserum. The apparent change in the pattern of DNA replication sites thus simply reflects the change in the spatial distribution of chromatin. The spatial pattern of DNA replication at the first S phase of the eggs fertilized after maturation was unique in that the whole nucleus was a mosaic of two distinct regions, each supposedly derived from the female and male pronuclei. The putative female region had a fibrillar pattern of DNA replication sites confined to the periphery of the nucleus, while the male region showed condensed sites of DNA replication, which persisted longer than the sites in the female pronuclear region. We discuss such a singularity of the first S phase in starfish eggs on the basis of the temporal relation between the progress of maturation and the time of activation. PMID- 8365568 TI - Ectopic spindle assembly during maturation of Xenopus oocytes: evidence for functional polarization of the oocyte cortex. AB - Inversion of stage VI Xenopus oocytes, when combined with cold-induced microtubule depolymerization, resulted in the displacement of the germinal vesicle (the oocyte nucleus) from its normal position in the animal hemisphere to a more equatorial or vegetal position. Confocal immunofluorescence microscopy with anti-tubulin antibodies revealed that the breakdown of ectopic germinal vesicles during progesterone-induced maturation of inverted oocytes was accompanied by the assembly of a transient MTOC-microtubule complex (MTOC-TMA complex) that migrated to the region of cortex nearest the site of GV breakdown. Formation of ectopic meiotic spindles, including spindle rotation and polar body formation, was observed with nearly equal frequency throughout the animal hemisphere. In contrast, the frequency of spindle formation in the vegetal hemisphere was substantially reduced. Many spindles that did form in more vegetal regions of the oocyte appeared unable to rotate and did not result in polar body formation. The results presented suggest that the assembly of meiotic spindles at the animal pole during maturation of Xenopus oocytes does not result from a specific targeting of the MTOC-TMA complex during oocyte maturation. However, the oocyte cortex does exhibit A-V polarization of its ability to support spindle rotation and polar body formation. Finally, the observed increase in the incidence of monaster formation in the vegetal hemisphere suggests that interactions between the nascent spindle and cortex may regulate spindle assembly and elongation. PMID- 8365569 TI - Crumbs and stardust act in a genetic pathway that controls the organization of epithelia in Drosophila melanogaster. AB - We provide evidence that the genes crumbs (crb) and stardust (sdt) encode critical components of a pathway that acts at the apical pole of epithelial cells to control the cytoarchitecture of ectodermally derived epithelia of the Drosophila embryo. We describe the developmental defects caused by sdt mutations, which are very similar to those associated with mutations in crb. In both mutants the epithelial structure of ectodermal cells breaks down during early organogenesis, leading to the formation of irregular clusters of cells and cell death in some epithelia. Certain cells can, however, compensate for the loss of crb or sdt function in a tissue-specific manner, later reassuming an epithelial cell shape and forming small epithelial vesicles, suggesting that, besides crb and sdt, other tissue-specific components are involved in this process. The crb protein (CRB) is continuously expressed in wild-type embryos in cells of the ectoderm and ectodermally derived epithelia. In sdt mutant embryos CRB is present only during gastrulation, but becomes undetectable during germ band extension; the protein is again visible during early organogenesis, at the time when the sdt mutant phenotype becomes apparent. In sdt mutant embryos, CRB is associated with the apical membrane only in well-differentiated epithelial cells, but it is expressed diffusely in the cytoplasm of cells which have lost epithelial morphology. Our results suggest that time- and tissue-specific control mechanisms exist to establish and maintain epithelial cell structure. Mosaic experiments suggest that sdt is required cell autonomously, in contrast to crb, the requirement of which appears to be non-cell-autonomous. Double mutant combinations of crb and sdt suggest that these genes are part of a common genetic pathway (crb/sdt pathway), in which sdt acts downstream of crb and is activated by the latter. PMID- 8365570 TI - Coordinate and noncoordinate regulation of synaptic vesicle protein genes during embryonic development. AB - Because the formation of a mature nerve terminal requires the accumulation of large quantities of synaptic vesicles, the expression of synaptic vesicle proteins would be expected to correlate with synaptogenesis. However, previous studies have provided conflicting evidence on this point. We have examined the developmental pattern of expression of mRNA and protein for three RNAs derived from two genes coding for synaptic vesicle membrane proteins. For these experiments, we cloned a chick p65 (synaptotagmin) cDNA using a reduced stringency screen with a rat p65 cDNA probe. We examined p65 expression in chick forebrain in conjunction with that of synaptophysin II. RNase protection assays for p65 and the two isoforms of synaptophysin II (Bixby, 1992) show essentially coordinate increases of these three mRNAs in embryonic forebrain during the peak period of synaptogenesis (E17 to E20). However, each of the three mRNAs has a distinct temporal pattern of expression during the early stages of embryogenesis. In the ciliary ganglion, upregulation of synaptophysin II mRNA correlates very well with synaptogenesis. Our results suggest that the regulation of expression of vesicle membrane protein mRNA can serve as a marker for synaptogenesis, despite temporal differences in early expression patterns. In contrast to mRNA expression, assays for vesicle protein expression show a relatively steady rise in both p65 and synaptophysin II throughout the embryonic period, without a sharp increase corresponding to that seen in message levels. These results suggest that the expression both of the p65 and of the synaptophysin II proteins is post transcriptionally regulated. PMID- 8365571 TI - The formation of the pronephric duct in Xenopus involves recruitment of posterior cells by migrating pronephric duct cells. AB - Cell migration and cell-cell interactions play important roles in numerous processes during embryogenesis. One of these is the formation of the pronephric (Wolffian) duct (PD), which connects the pronephros to the cloaca. It is currently accepted that in most amphibians the pronephric duct is formed by active migration of the pronephric duct rudiment (PDR) cells along a predetermined pathway. However, there is evidence that in Xenopus, the PD may be formed entirely by in situ segregation of cells out of the lateral mesoderm. In this study, we show, using PDR ablation and Xenopus laevis-Xenopus borealis chimeras, that PD elongation in Xenopus requires both active cell migration and an induced recruitment of cells from the posterior. We also show that PDR cell migration is limited to only a few stages during development and that this temporal control is due, at least in part, to changes in the competence of the PD pathway to support cell migration. PMID- 8365572 TI - Effects of the neurotrophins and CNTF on developing statoacoustic neurons: comparison with an otocyst-derived factor. AB - During the early stages of auditory development, the inner ear (otocyst) releases an unidentified, diffusible factor that promotes neurite outgrowth from the associated statoacoustic ganglia (SAG). Using a variety of criteria, the present study compared the neurite- and survival-promoting properties of this otocyst derived factor (ODF) to the neurotrophins NGF, BDNF, NT-3, and NT-4 and ciliary neurotrophic factor (CNTF). Ganglia known to respond to specific growth factors were cultured in the presence of ODF. ODF failed to promote neurite outgrowth from trigeminal, ciliary, sympathetic, or dorsal root ganglia, suggesting that ODF may have properties different from other identified growth factors. In complementary experiments, SAG explants were cultured in ODF, the neurotrophins, and CNTF. The extent of outgrowth was greatest in the presence of ODF and CNTF, with the neurotrophins having little effect. In neuron-enriched, dissociated cell cultures, ODF promoted both survival and outgrowth of SAG neurons. However, neither the neurotrophins nor CNTF, alone or in combination, promoted the survival or outgrowth of dissociated SAG neurons. Thus, the outgrowth seen in the explant cultures appears to be due to indirect effects via the ganglionic nonneuronal cells. The addition of anti-NGF antisera failed to block the activity of chick, rat, or mouse ODF, further indicating that NGF is not the primary component of ODF. Together, the results of this study indicated that the properties of the ODF are not mimicked by the neurotrophins or CNTF. PMID- 8365573 TI - Requirements for promoter activity in mouse oocytes and embryos distinguish paternal pronuclei from maternal and zygotic nuclei. AB - Fertilization of mouse eggs produces a 1-cell embryo containing both a paternal and maternal pronucleus. These two nuclei combine during the first mitosis to form the zygotic nuclei of 2-cell embryos. This transition is accompanied by the onset of transcription and the decline of maternal mRNA-dependent gene expression. To determine how changes in nuclear composition affect gene expression, plasmid DNA containing a promoter and an enhancer that function throughout a broad host range was injected into nuclei of oocytes and embryos. The requirements for promoter activity in paternal pronuclei of 1-cell embryos were distinct from those in maternal or zygotic nuclei: (1) Paternal pronuclei permitted high levels of promoter activity relative to maternal or zygotic nuclei. (2) Butyrate, an agent that alters chromatin structure, stimulated promoter activity in maternal or zygotic nuclei, but not in paternal pronuclei. (3) The embryo-responsive polyomavirus F101 enhancer also stimulated promoter activity, but only after formation of a 2-cell embryo. Either butyrate or the F101 enhancer stimulated promoter activity in zygotic nuclei to the level observed in paternal pronuclei. Stimulation also was observed with 2-cell embryos containing nuclei of only maternal or paternal origin, but their transcriptional capacity was more limited. These and other results support the hypothesis that the need for enhancers in 2-cell embryos results from repression by chromatin structure, and the role of enhancers is to relieve this repression. PMID- 8365574 TI - Development of the neural crest in the zebrafish. AB - The embryonic zebrafish is rapidly becoming an important model system for studies of early events in vertebrate development. We review recent work describing the development of zebrafish neural crest and experimental studies examining the cellular, molecular, and genetic mechanisms of crest development. PMID- 8365575 TI - The role of cell-cell and cell-matrix interactions in the morphogenesis of the neural crest. AB - The neural crest is an excellent model system with which to study the molecular controls of morphogenesis. Neural crest cells initiate their migration from the dorsal portion of the neural epithelium owing to an epithelial-mesenchymal transformation. They then followed stereotyped pathways for long distances before reaching their multiple destinations, and they cease migration in defined regions where they undergo terminal differentiation. Recent experimental evidence, which is summarized in this review, suggests that these various steps in neural crest morphogenesis are influenced by cell-cell and cell-matrix adhesions. Future studies employing genetic mutants and molecular techniques should provide more direct evidence for the role of cell-cell and cell-matrix interactions in neural crest morphogenesis. PMID- 8365576 TI - The characterization of astrocyte cell lines that display properties of glial scar tissue. AB - The glial scar has been proposed to be a major impediment to regeneration in the adult CNS. Analysis of glial scars in vivo is complicated, however, by the large number of cell types present in such lesions. We have attempted to simplify analysis of the glial scar environment by deriving a series of conditionally immortal astrocyte cell lines that display several properties expressed by glial scar tissue in vitro. The astrocyte lines, which were derived from H-2KbtsA58 transgenic mice, expressed macromolecules associated with glial scars in vivo and were significantly less effective than neonatal astrocytes at promoting neurite outgrowth from postnatal central and peripheral neurons. The astrocyte lines also inhibited migration of oligodendrocyte type-2 astrocyte progenitor cells in vitro. We propose that certain properties shown previously to be expressed by glial scars may be reconstituted in vitro by astrocytes alone. PMID- 8365577 TI - Methoxyacetaldehyde, an intermediate metabolite of 2-methoxyethanol, is immunosuppressive in the rat. AB - 2-Methoxyethanol (ME) is metabolized to 2-methoxyacetic acid (MAA) via the intermediate metabolite methoxyacetaldehyde (MAAD). Both ME and MAA have been shown in this laboratory to be immunosuppressive in rats following oral dosing. In this study, the plaque-forming cell (PFC) response to trinitrophenyl lipopolysaccharide (TNP-LPS) was used to determine if MAAD is immunosuppressive in rats. Rats pretreated with the aldehyde dehydrogenase inhibitors disulfiram (2 mmol/kg) or cyanamide (0.48 mmol/kg) followed by oral dosing with ME (2.64 mmol/kg) resulted in suppressed PFC responses equivalent to the suppressed responses of rats dosed with ME alone. Rats pretreated with disulfiram and then dosed with 2.64 mmol/kg 2-methoxyethyl acetate (MEA), also resulted in suppressed PFC responses similar to that of MEA alone. In contrast, coadministration of the alcohol dehydrogenase inhibitor 4-methylpyrazole (1.2 mmol/kg) with ME or MEA blocked suppression of the PFC response following exposure to ME or MEA alone. Oral dosing with equimolar (2.64 mmol/kg) concentrations of ME, MAA, or MAAD resulted in equivalent suppression of the TNP-LPS PFC response. Rats exposed to either disulfiram or cyanamide and MAAD also resulted in suppression of the PFC response. These results indicate that metabolism of ME to either MAAD or MAA is required for immunosuppression, and that these two metabolites are equipotent immunosuppressants in the rat. PMID- 8365578 TI - Toxicokinetics of intravenous methanol in the female rat. AB - The toxicokinetics of intravenously administered methanol were examined in female Sprague-Dawley rats. Animals received a single administration of 100, 500, or 2500 mg methanol/kg; the two lower doses were administered as a bolus, while the high dose was administered over 1.5 min. A small (approximately 3%) but statistically insignificant (p > 0.1) degree of transpulmonary methanol extraction, expressed as the fractional arterial-venous difference in concentration, was observed after administration of 250 mg methanol/kg. The elimination of methanol from the systemic circulation was markedly nonlinear, suggestive of a significant capacity-limited route of elimination. A single set of kinetic parameters (apparent distributional volume of the central compartment [Vc], intercompartmental transfer rate constants [k12 and k21], and Vmax and Km for elimination) described the blood methanol concentration-time data from rats receiving the 100 and 500 mg/kg doses. Blood methanol concentrations declined much more rapidly in animals receiving the 2500 mg/kg dose than would be predicted from the kinetic parameters derived from the other two experimental groups. The data from the 2500 mg/kg group could be described adequately by a kinetic model incorporating parallel first-order and saturable elimination processes. A portion of this apparent linear elimination pathway was due to renal excretion of the unchanged alcohol. The presence of both linear and nonlinear elimination pathways for methanol may have implications regarding high-dose to low-dose toxicologic extrapolations. PMID- 8365579 TI - DMBA induces programmed cell death (apoptosis) in the A20.1 murine B cell lymphoma. AB - The mechanism by which 7,12-dimethylbenz[a]anthracene (DMBA) produces cytotoxicity in lymphocytes was investigated in these studies using the murine A20.1 B cell lymphoma. Results show that in vitro exposure of these cells to 10 30 microM DMBA for 4 hr produced an increase in intracellular Ca2+, DNA fragmentation, and subsequent cell death. Elevation of Ca2+ and DNA fragmentation induced by DMBA were greatly pronounced when the A20.1 cells were exposed at high cell density (10(7) cells/ml). DMBA-induced DNA fragmentation and cell death were inhibited by coexposure of A20.1 cells to a calcium chelator (EDTA), a general nuclease and polymerase inhibitor (aurintricarboxylic acid), and a protein synthesis inhibitor (cycloheximide). These agents have been previously shown to inhibit apoptosis in lymphocytes and other cells exposed to chemical agents. We also found that cyclosporin A, an inhibitor of Ca(2+)-dependent pathways of T and B cell activation, prevented apoptosis in the A20.1 cell line. These results demonstrate that DMBA induces programmed cell death (apoptosis) in the A20.1 murine B cell lymphoma by Ca(2+)-dependent pathways. The increased sensitivity of A20.1 at high cell density to Ca2+ elevation and DNA fragmentation suggests that cell to cell interactions may also be important in this process. PMID- 8365580 TI - Production of metallothionein and heat-shock proteins in response to metals. AB - Acute stress, such as heat, and some metals, such as arsenite, will induce a specific group of stress proteins referred to as heat-shock proteins. The heat shock proteins contribute to the survival of cells following a variety of stresses. Similarly, metals such as cadmium and zinc, will increase the levels of metallothionein (MT). The metal-binding protein, MT, has also been found to have a protective role in the cellular response to acute stresses like heavy metals. The purpose of the present study was to examine the production of these proteins in response to metals. Rat hepatocytes were maintained in monolayer culture for 22 hr, and subsequently treated with various concentrations of metals for 4 hr, or incubated at 43.5 degrees C for 15-60 min. Following two washes with fresh media, the cells were labeled with [35S]-methionine (25 microCi/ml) in methionine free media for 4 hr for determination of heat-shock protein production, or reincubated in fresh media for 20 hr for MT determination. Heat-shock protein production was determined by SDS-polyacrylamide gel electrophoresis followed by autoradiography. The autoradiograms were quantified by densitometric scanning. MT was determined by the Cd/hemoglobin affinity assay. Three metals (arsenite, cadmium, and zinc) strongly increased the heat-shock proteins. Whereas arsenite was a much less effective inducer of MT than was cadmium or zinc, arsenite was as effective as the other metals in inducing heat-shock proteins. Nickel was a good inducer of MT; however, it resulted in only a slight increase in the levels of heat-shock proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365581 TI - DNA-carcinogen adducts in circulating leukocytes as indicators of arylamine carcinogen exposure. AB - DNA-carcinogen adducts in leukocytes and putative target tissues (liver and urinary bladder) of C57BL/6J mice were measured by 32P-postlabeling and HPLC analysis after controlled exposure to the arylamine carcinogen 2-aminofluorene (2 AF). After an acute exposure via ip injection, adducts were detected at 3 hr in leukocytes, liver, and bladder. The disappearance of DNA-carcinogen adducts in liver and leukocytes were parallel over the 24-hr period studied. Following a 7 day continuous exposure to 2-AF via drinking water, adduct levels in leukocytes and target tissues were responsive to dose at 30, 100, and 300 ppm. Adduct levels at the highest dose reached 17,000 fmol/mg DNA in leukocytes, 1900 fmol/mg in liver, and 2300 fmol/mg in bladder. Although adduct levels after 7 days were highest in leukocytes, adducts were not detectable in leukocytes 7 days after discontinuing exposure. In contrast, liver and bladder retained approximately 50 and 75% of their respective adduct levels 7 days after exposure was stopped. The results indicate that circulating leukocytes may be useful as indicators of current exposure to arylamine carcinogens. Circulating leukocytes may also be useful as biological monitors of DNA damage in arylamine target tissues during chronic exposure to these compounds. Some important differences in persistence of DNA-carcinogen adducts between leukocytes and target tissues were observed. PMID- 8365582 TI - Respiratory and immunological responses of guinea pigs to enzyme-containing detergents: a comparison of intratracheal and inhalation modes of exposure. AB - Guinea pigs were exposed once a week for 10 weeks by intratracheal exposure to solutions of 3, 1, 0.3, or 0.1 micrograms of the enzyme protein, Subtilisn Carlsberg (Alcalase), in 250 micrograms of a detergent base. Other groups of guinea pigs were exposed by inhalation (6 hr per day, 4 days a week) to 1 mg/m3 of the aerosolized detergent base containing either 3.5, 1.1, 0.3, or 0.1% Alcalase protein. Evaluations of gross respiratory responses immediately following each intratracheal exposure revealed a significant dose response in respiratory symptoms measurable after the fourth exposure and continuing throughout the study. In the inhalation experiment, during Weeks 4 through 10, animals were observed to have respiratory symptoms which were dependent upon both the dose of enzyme and on total exposure to the enzyme/detergent atmosphere. For both intratracheal and inhalation routes of exposure, the initial appearance of respiratory symptoms coincided with the first appearance of measurable serum allergic antibodies specific to Alcalase. The allergic antibody levels increased with time and dosage by both routes of exposure, and the antibody titers generated by the intratracheal administration of antigen were comparable to those generated by the inhalation route of exposure. These results indicate that the intratracheal technique is appropriate for the evaluation of the respiratory allergic response to a protein. PMID- 8365583 TI - The encapsulation of squid diisopropylphosphorofluoridate-hydrolyzing enzyme within mouse erythrocytes. AB - This study describes the entrapment of squid-type diisopropylphosphorofluoridate hydrolyzing enzyme (DFPase) within mouse red blood cells. These erythrocytes thereby gain the ability to rapidly hydrolyze alkylphosphate cholinesterase (ChE) inhibitors such as diisopropyl fluorophosphate (DFP). DFPase rapidly hydrolyzes DFP to diisopropyl phosphate. Resealed erythrocytes provide a stable carrier system that can preserve the activity of encapsulated enzymes against otherwise rapid in vivo degradation; thus, ChE inhibitors can be degraded to relatively nontoxic metabolites by these erythrocyte carriers. Squid DFPase was purified from the hepatopancreas of Atlantic squid and DFPase activity was determined by measuring changes in fluoride ion concentration using a fluoride ion selective electrode. Mouse erythrocytes in suspension with excess squid DFPase were dialyzed against hypotonic buffer to allow the encapsulation of the enzyme to occur. Cells were then resealed by returning the suspension to isosmotic with saline. Rate of DFP hydrolysis observed with these cells was much greater than the rate of nonenzymatic hydrolysis and was directly proportional to the amount of the erythrocyte suspension added to the assay solution. The rate of hydrolysis was first order in substrate. Erythrocyte controls showed no endogenous DFPase activity. These results suggest that enzyme entrapment may be developed as a method to prevent and antagonize organophosphate poisoning. PMID- 8365584 TI - Chronic toxicity and carcinogenicity studies of 1-methylnaphthalene in B6C3F1 mice. AB - The carcinogenic potential of 1-methylnaphthalene (1-MN), a compound which exists widely in the environment, was investigated in B6C3F1 mice. Groups of 50 male and 50 female mice were given diets containing 0, 0.075, or 0.15% 1-MN for 81 weeks. Both treatment groups developed pulmonary alveolar proteinosis at high incidence, with 46.0 and 34.7% of females and 46.0 and 38.0% of males, respectively, being affected. Total lipid and phospholipid levels in sera and monocytes in peripheral blood were also significantly increased in 1-MN-treated female and male mice in contrast with control values. The incidences of bronchiolar/alveolar adenomas in the lungs of male mice given both 0.075 or 0.15% 1-MN were 26.0 and 24.0%, respectively, in both cases significantly increased in contrast with the 4.1% observed for control males. However, neither dose dependence nor significant difference in the incidences of bronchiolar/alveolar carcinomas between 1-MN treated and control male mice was observed. The incidences of other tumors also were similar in both 1-MN-treated and control groups. The results of the present experiment thus suggested a possible weak carcinogenic potential of 1-MN to the lung of male but not female B6C3F1 mice. PMID- 8365585 TI - Application of the tukey trend test procedure to assess developmental and reproductive toxicity. I. Measurement data. AB - Developmental and reproductive (DAR) toxicity studies typically include a series of increasing doses of a compound and a zero dose control. Given this framework, Tukey et al. (Biometrics, 41, 295-301, 1985) proposed a procedure (referred to as either the Tukey trend or TCH test procedure) for detecting a nonzero trend in response to increasing doses of the test compound. The procedure considers three candidate dosage scalings to ensure high power against relatively common dose response patterns and appreciable power against most reasonable patterns. For toxicologic effects with near monotonic dose-response patterns, simulation studies have shown the TCH test to be overall more powerful than pairwise comparison procedures. The TCH test can be applied sequentially, eliminating the highest dose each time a statistically significant trend is observed, until a no statistical-significance-of-trend dose is reached. This is the highest dose through which there is no statistically trustworthy evidence of the compound's impact on the response. Since DAR toxicity usually exhibits a progressive (monotonic) dose-response, we advocate routine use of Tukey's trend test for the evaluation of treatment effects in these studies. In this article, we discuss the procedure in detail and apply it to fetal body weight, a continuous measurement variable, from a developmental toxicity study. PMID- 8365586 TI - Nephrotoxicity of pravadoline maleate (WIN 48098-6) in dogs: evidence of maleic acid-induced acute tubular necrosis. AB - Single oral administration of pravadoline maleate (WIN 48098-6), the maleic acid salt of WIN 48098, induced acute tubular necrosis (ATN) in male and female beagle dogs at dosages > or = 40 mg/kg (WIN 48098 base (31 mg/kg) and maleic acid (9 mg/kg)). Subsequent oral studies were conducted with equimolar dosages of maleic acid and WIN 48098-7, the ethanesulfonate salt of WIN 48098, to determine the nephrotoxic moiety of WIN 48098-6. ATN was observed for dogs given only maleic acid at single oral dosages > or = 9 mg/kg. This result provided evidence that maleic acid was responsible for the nephrotoxicity observed in dogs given single oral dosages of WIN 48098-6. The induction of maleic acid-related nephrotoxicity in dogs may confound the interpretation of toxicologic studies of maleic acid salts of basic pharmaceutics, if the dosage of test article results in the delivery of dosages of maleic acid > or = 9 mg/kg. Furthermore, the results of these studies underscore the importance of establishing maximum no-observed effect dosages and target organ toxicity profiles for acids and bases that are commonly used in the development of salts of pharmaceutics. PMID- 8365587 TI - Quaternary silsesquioxane: a developmental toxicity study in rats. AB - The developmental toxicity of an antimicrobial organosilicon quaternary ammonium chloride (Quaternary Silsesquioxane) was evaluated in rats. Groups of 25 pregnant CD rats were administered 100, 300, or 1000 mg/kg/day of test material by gavage as a single daily dose on Days 6 through 15 of gestation at a volume of 10 ml/kg. The control group received only corn oil as the vehicle. Cesarean examinations were performed on all females on Gestation Day 20 followed by evaluation of the fetuses for teratogenicity. Maternal effects included a slight but statistically significant increase in relative liver weights at the 1000 mg/kg/day dose level. Using these hepatic changes as an adverse effect, the maternal no observable adverse effect level for this study was identified at 300 mg/kg/day. The number of corpora lutea, implantation sites, viable fetuses, and early and late resorptions, the fetal body weights, the crown-rump length, and the gravid uterine and corrected body weights were not affected by the administration of Quat-Silsesquioxane. The occurrence of external and internal soft tissue malformations and variations and the incidences of skeletal malformations and variations in the treated groups were not significantly different from those in the control group. These results demonstrated that oral administration of Quat Silsesquioxane as high as 1000 mg/kg/day did not produce teratogenicity or other indications of developmental toxicity in the rat conceptus. PMID- 8365588 TI - Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests. AB - We have reported on the design and content of a screening battery using a "tier" approach for detecting potential immunotoxic compounds in mice (Luster et al., Fundam. Appl. Toxicol., 10, 2-19, 1988). The data base generated from these studies, which consists of over 50 selected compounds, has been collected and analyzed in an attempt to improve future testing strategies and provide information to aid in developing future quantitative risk assessment for immunotoxicity. In a recent study it was shown that as few as two or three immune parameters were needed to predict immunotoxicants in mice (Luster et al., Fundam. Appl. Toxicol., 18, 200-210, 1992). In particular, enumeration of lymphocyte populations and quantitation of the T-dependent antibody response were particularly beneficial. Furthermore, commonly employed apical measures (e.g., leukocyte counts, lymphoid organ weights) were fairly insensitive. The present analyses focus on the use of this data base to develop statistical models that examine the qualitative and quantitative relationship(s) between the immune function and host resistance tests. The conclusion derived from these analyses are: (1) A good correlation exists between changes in the immune tests and altered host resistance in that there were no instances where host resistance was altered without affecting an immune test(s). However, in some instances immune changes occurred without corresponding changes in host resistance. (2) No single immune test could be identified which was fully predictive for altered host resistance, although most assays were relatively good indicators (i.e., > 70%). Several others, such as proliferative response to lipopolysaccharide and leukocyte counts, were found to be relatively poor indicators for host resistance changes. (3) The ability to resist infectious agent challenge is dependent upon the degrees of immunosuppression and the quantity of infectious agent administered. (4) Logistic and standard regression modeling using one extensive chemical data set from the immunosuppressive agent, cyclophosphamide, indicated that most immune function-host resistance relationships followed linear rather than linear-quadratic (threshold-like) models. For most of the relationships this could not be confirmed using a large chemical data set and, thus, a more mechanistically based approach for modeling will need to be developed. (5) Using this limited data set, methods were developed for modeling the precise quantitative relationships between changes in selected immune tests and host resistance tests. PMID- 8365589 TI - Are mouse strains differentially susceptible to the reproductive toxicity of ethylene glycol monomethyl ether? A study of three strains. AB - Most rodent reproductive toxicology studies utilize strains of high fecundity. These studies were conducted to examine the possibility that mouse strains of differing fecundity would respond differently to a known reproductive toxicant. Thirty pairs each of Swiss CD-1, C57B1, and C3H mice were cohabited for 14 weeks while consuming 0, 0.03, 0.10, or 0.30% EGME in the drinking water. Litter data were collected during cohabitation. Body and organ weights, and various sperm data, were collected at necropsy, and second-generation fertility was evaluated. The data show that the most fecund strain (Swiss) was affected the least by exposure to EGME, while the least fecund strain (C3H) suffered the greatest declines in fertility. These differences might alter interspecies extrapolation factors, or the permissible exposure levels for humans. PMID- 8365590 TI - Bioavailability of arsenic in soil impacted by smelter activities following oral administration in rabbits. AB - This study determined the extent of arsenic (As) absorption from soil from Anaconda, Montana. Prepubescent male and female SPF New Zealand White rabbits (5/sex/group) were given a single oral (capsule) administration of soil (3900 ppm As) at three different dose levels (0.2, 0.5, and 1.0 g of soil/kg, corresponding to 0.78, 1.95, and 3.9 mg As/kg, respectively). Standard groups included untreated controls, an intravenous sodium arsenate group (1.95 mg As/kg), and a gavage sodium arsenate group (1.95 mg As/kg). Urine, cage rinse, and feces were collected at 24-hr intervals for 5 days and were analyzed for total As concentration. Clinical signs, body weights, and food consumption for treated animals were similar to controls. Maximum As concentrations were obtained over the initial 24-hr collection interval. A dose-dependent delay in urinary As excretion, the major elimination pathway, was observed in the oral soil group compared to that in the gavage group. For the animals in the soil groups, approximately 80% of the administered As dose was eliminated in the feces compared to approximately 10 and 50% for the intravenous and oral gavage groups, respectively. The relative oral bioavailabilities (+/- SD) of As in the gavage and test soil groups based on comparison with excreta data from the intravenous group were approximately 50 +/- 5.7 and 24 +/- 3.2%, respectively (after normalization of intravenous group's As recovery data to 100%). These results indicated that As in the soil was probably in a less soluble and therefore a less absorbable form than sodium arsenate. PMID- 8365591 TI - Metabolism of acrylic acid to carbon dioxide in mouse tissues. AB - Acrylic acid (AA) is acutely irritating at sites of initial contact but causes little systemic toxicity probably due to its rapid metabolism to CO2 and acetyl CoA via a secondary pathway of propionic acid catabolism. In this study, the rate of AA oxidation in 13 tissues of C3H mice was measured by incubating tissue slices with [1-14C]AA and collecting, 14CO2. Oxidation of AA followed pseudo Michaelis-Menten kinetics in the liver, kidney, and skin. Pseudo-Km values were similar among these tissues and averaged 0.67 mM. The maximal rate of AA oxidation in kidney, liver, and skin was 2890 +/- 436 (mean +/- SE, N = 3), 616 +/- 62, and 47.9 +/- 5.8 nmol/hr/g, respectively. The remaining organs oxidized AA at rates less than 40% of the rate in liver. Rates of metabolism in tissues from male and female mice were similar. 3-Hydroxypropionic acid was the only metabolite detected by high-performance liquid chromatographic analysis following incubation of tissues with [1-14C]AA. Kidney and liver also oxidized [2,3-14C]AA and [1-14C]acetate well, thus providing for the complete metabolism of AA carbons to CO2. These results demonstrate that the rate of AA metabolism varies significantly among mouse tissues and suggest that the kidneys and liver are major sites of detoxification of AA. PMID- 8365592 TI - Are hyperplastic rectosigmoid polyps associated with an increased risk of proximal colonic neoplasms? AB - Diminutive polyps are frequent findings on screening flexible sigmoidoscopy. To determine the significance of distal diminutive polyps, we conducted a prospective study of 162 asymptomatic, average-risk subjects who were 50 years of age or older. Subjects were divided into four groups: 42 control subjects with no polyps in the rectosigmoid, 66 subjects with at least one diminutive adenoma in the rectosigmoid, 12 subjects with a mixed hyperplastic-adenomatous polyp in the rectosigmoid, and 42 subjects with only hyperplastic polyps in the rectosigmoid. Total colonoscopy was performed on all subjects. The prevalence of proximal adenomas was 42% in the adenoma group, 25% in the mixed group, 14% in the hyperplastic group and 12% in the control group. The prevalence of proximal adenomas was significantly higher (p = 0.006) in the adenoma group as compared with the control and hyperplastic groups. Increasing age was associated with an increased prevalence of proximal adenomas. Nearly two thirds of those over 65 years of age with distal diminutive adenomas had proximal colonic neoplasms. These results indicate that diminutive rectosigmoid adenomas are good markers for proximal neoplasms. Rectosigmoid hyperplastic polyps are not associated with an increased prevalence of proximal neoplasms. Total colonoscopy is not indicated if hyperplastic polyps are the only finding on flexible sigmoidoscopy. PMID- 8365593 TI - Sphincter of Oddi manometry: interobserver variability. AB - To determine the frequency and magnitude of interobserver variability, 50 sphincter of Oddi manometry tracings were read by three separate physicians experienced in reading such manometry. Ninety station pull-throughs were read, and attention was focused on the reference duodenal baseline pressure and two methods of reading the basal sphincter pressure. A high degree of correlation was found among the three observers with correlation coefficients of > 0.9 for reading baseline duodenal and basal sphincter pressures. Differences in basal sphincter pressure readings were greatest in patients with very high basal sphincter pressure. The most clinically relevant parameter was thought to be the mean basal sphincter pressure. All three observers agreed on normal (mean basal pressure < or = 40 mm Hg) versus abnormal (mean basal pressure > 40 mm Hg) in 82% to 90% of tracings. When the definition of agreement was broadened to include patients with pressures of 40 +/- 3 mm Hg (37 to 43 mm Hg), the observers agreed 87% to 94% of the time. Overall, these findings are thought to indicate that interobserver variability for reading sphincter of Oddi manometry is minimal when the observers are experienced in reading these tracings. PMID- 8365594 TI - Sphincter of Oddi dysfunction in patients with intact gallbladder: therapeutic response to endoscopic sphincterotomy. AB - Increasing evidence exists of the occurrence of sphincter of Oddi dysfunction in patients with an intact gallbladder. Optimal therapy for such patients has not been defined. From 1989 to 1991, 35 patients with sphincter of Oddi dysfunction (abnormal basal sphincter pressure > 40 mm Hg) and an intact gallbladder were identified. The patients with abnormal ductography (except for duct dilation), pancreas divisum, or pancreato-biliary malignancy were excluded. All patients had disabling upper abdominal pain, which was quantified on a 0 = none to 10 = severe pain scale. All patients received standard endoscopic biliary sphincterotomy and were followed up for 4 to 26 months with a mean of 13 months. Initially, 27 of 35 patients (77%) showed at least 50% improvement in the pain score, whereas only 15 of the 27 remained improved throughout the follow-up interval. Patients who were unimproved or had relapses were offered cholecystectomy and 11 patients underwent the procedure. These patients were followed up after cholecystectomy for 2 to 24 months, with a mean of 13 months. Eight of 11 were improved. In summary, the combination of endoscopic sphincterotomy and selective cholecystectomy and minimal medical treatment resulted in a good and excellent response rate of 68%. Better techniques are needed to select patients who will respond to these therapies. PMID- 8365596 TI - High-resolution 25-megahertz ultrasonography of the gastrointestinal wall: histologic correlates. AB - High-frequency ultrasonography (25 MHz) with histologic correlation was used to examine surgical specimens from the gastrointestinal tract. Although the stomach, colon, and rectum demonstrated the usual five-layered appearance, we found that the esophagus had additional layers when imaged with the high-resolution probe. These layers correspond to the following: (1) superficial epithelium, (2) deep epithelium, (3) lamina propria plus the acoustic interface echo between the lamina propria and muscularis mucosa, and (4) muscularis mucosa minus the acoustic interface echo between the lamina propria and muscularis mucosa. This pattern is not found in regions of the gastrointestinal tract where the muscularis mucosa is relatively thin compared with the axial resolution of the ultrasound system. These results suggest that within the esophagus additional structural information may be obtained when higher-resolution ultrasound systems are used. PMID- 8365595 TI - The incidence of post-sphincterotomy stenosis in group II patients with sphincter of Oddi dysfunction. AB - Patients with group II sphincter of Oddi dysfunction documented by elevated sphincter of Oddi pressure improve after endoscopic sphincterotomy. A large group II population was studied to determine the incidence of post-endoscopic sphincterotomy stenosis. Eighty-five patients (82 women and 3 men), ages 21 to 88 years (mean, 50 years), fulfilled the clinical criteria for group II sphincter of Oddi dysfunction; each had an elevated basal sphincter of Oddi pressure (> or = 40 mm Hg), and received endoscopic sphincterotomy. These patients were observed for a mean of 7 +/- 3 years. Four patients re-presented with clinical findings suggestive of recurrent sphincter of Oddi dysfunction; all were found to have a basal sphincter of Oddi pressure greater than or equal to 40 mm Hg. Symptoms re developed within 4 months after endoscopic sphincterotomy (mean, 3.3 months). Endoscopic sphincterotomy was repeated in all four patients with one endoscopically treated complication. On 25-month mean follow-up, none of the patients had further signs or symptoms of papillary stenosis. Endoscopic sphincterotomy in patients with group II sphincter of Oddi dysfunction is associated with a low incidence of restenosis (4.7%). Repeat endoscopic sphincterotomy was found to be effective management in patients with papillary restenosis. PMID- 8365597 TI - Delineation of the gastric muscularis mucosae and assessment of depth of invasion of early gastric cancer using a 20-megahertz endoscopic ultrasound probe. AB - Using a 20 MHz endoscopic ultrasound system, delineation of the gastric muscularis mucosae and estimation of the depth of malignant invasion was attempted by in vivo scanning during the process of routine endoscopic observation or in vitro scanning of excised sections of 34 early gastric cancers in 32 patients. The muscularis mucosae was visualized as a single hypoechoic layer in 16 of 32 lesions (50%) scanned in vitro. Comparison of lesions in which delineation of the muscularis mucosae was or was not possible revealed no significant differences with respect to either the thickness of the lamina propria and muscularis mucosae or with respect to the degree of inflammatory cell infiltration of the lamina propria or the conditions of the boundary between the lamina propria and the muscularis mucosae. This indicates that improvement of the operability characteristics of the ultrasonic apparatus will be needed to achieve improved delineation of the muscularis mucosae. The accuracy of invasion depth estimation of early gastric cancer was 67% (16 of 24 lesions scanned in vivo) and 73% (8 of 11 lesions) in cases in vivo where the muscularis mucosae and the tumor were delineated on the same screen. The principal factors causing erroneous staging were the presence of dilated benign glandular ducts, ulcer scars, and attenuation of the ultrasound waves. PMID- 8365598 TI - Endoscopic Nd:YAG laser coagulation of bleeding from radiation proctopathy. AB - Hematochezia from mucosal vascular lesions usually confined to the rectum represents an uncommon but problematic late complication of pelvic radiotherapy. We studied 47 patients with medically refractory hematochezia resulting from radiation-induced rectosigmoid mucosal vascular lesions. All lesions were endoscopically coagulated with Nd:YAG laser. Median duration of hematochezia before laser therapy was 11 months, despite previous medical treatment (98%) or bypass colostomy (6%). Within 3 to 6 months after laser treatment, the number of patients with daily hematochezia fell from 40 (85%) to 5 (11%; p < 0.001), and the median hemoglobin level increased from 9.7 gm/dl to 11.7 gm/dl (p < 0.001). Complications occurred in three patients (6%); no deaths occurred. The condition in six patients (12.8%) was not improved by laser treatment. Two patients (4%) ultimately required surgical treatment for bleeding control. On the basis of symptomatic, hematologic, and endoscopic responses, Nd:YAG laser photocoagulation controlled bleeding from radiation proctopathy in most patients with an acceptably low morbidity. Patients with sigmoid colon involvement responded less favorably. Endoscopic laser photocoagulation should be considered before surgical intervention for treatment of hematochezia from radiation proctopathy. PMID- 8365599 TI - The frequency of total colonoscopy and terminal ileal intubation in the 1990s. AB - We examined the frequency of total colonoscopy and terminal ileal intubation in a training setting using modern videoendoscopic equipment and techniques with examinations supervised or done by the two authors. The cecum was considered reached if the endoscopic report included a description of the cecal landmarks visualized and if electronic images documenting these landmarks were obtained. One of us also routinely attempted terminal ileal intubation for documentation purposes, allotting a minute or two for the purpose. In cases of chronic diarrhea and possible inflammatory bowel disease, a more prolonged attempt was made to visualize the terminal ileum. Among 418 consecutive colonoscopies, the cecum was reached in 96% of cases. If cases of malignant obstruction were excluded, the success rate improved to 97%. When routinely attempted, the terminal ileum was intubated and inspected in 74% of cases (excluding cases of malignant obstruction). In cases in which terminal ileal intubation and inspection was deemed necessary, the success rate was 91%. We conclude that total colonoscopy can be accomplished in the 1990s in excess of 90% of cases and can be documented by high-quality photographs that can be attached to the procedure report. High rates of successful total colonoscopy should be attainable even in training programs. Routine intubation of the terminal ileum can be performed to provide further objective proof of the extent of colonoscopy and to allow the endoscopist to develop and maintain the skill. A skilled, practiced endoscopist can inspect the terminal ileum in about 90% of cases in which such examination is needed. PMID- 8365600 TI - Endoscopic ultrasonography in the diagnosis of colorectal cancer invasion. AB - Endoscopic ultrasonography was pre-operatively performed in 164 patients with colorectal cancer, and the resected specimens confirmed to be cancerous histologically. Normal colorectal wall was visualized by endoscopic ultrasonography as a five-layered structure. The first, third, and fifth layers were hyperechoic, and the second and fourth layers were hypoechoic. The first and second layers comprised the mucosa, the third layer the submucosa, the fourth layer the muscularis propria, and the fifth layer the subserosa and serosa (adventitia). By this technique, cancer of the colon appeared as a hypoechoic mass with an intermediate echo level between the third hyperechoic and fourth hypoechoic layers. Endoscopic ultrasonographic determination of the depth of tumor invasion was based on abnormal changes of these layered structures and adjacent organs. Overall, the accuracy rate of endoscopic ultrasonography in the diagnosis of the depth of colorectal cancer was 83%. A hypoechoic round mass adjacent to the cancer was interpreted as a metastatic lymph node. The sensitivity and specificity of endoscopic ultrasonography in the diagnosis of lymph node metastasis were 68% and 70%, respectively. The overall accuracy rate of tumor staging by endoscopic ultrasonography according to Dukes' classification was 62%. Endoscopic ultrasonography is a valuable tool in the management of colorectal cancer. It has a high accuracy rate in determining the depth of tumor invasion. The pre-operative information obtained with this tool may influence the choice of therapy. PMID- 8365601 TI - Treatment of non-extractable common bile duct stones with combination ursodeoxycholic acid plus endoprostheses. AB - Despite widely available technology for removal of bile duct stones, endoscopists currently encounter approximately 3% of patients with stones that defy extraction. After sphincterotomy and unsuccessful attempts at extraction of "defiant" stones, biliary stents were placed in 22 patients. Ten patients were treated with ursodeoxycholic acid, and 12 patients treated only with stent served as control subjects. Ductal strictures preventing stone extraction were present in eight control patients and in six patients treated with ursodeoxycholic acid. The number of total calculi in the ursodeoxycholic acid group was slightly higher (4.2 per patient) than the number in the control group (3.3 per patient). Stone and bile duct dimensions were similar in each group. Nine of 10 patients in the ursodeoxycholic acid group had complete stone clearance, and 41 of 42 stones were removed during a follow-up period of 9 +/- 2 months; in contrast, no patient in the control group had complete clearance and only 6 of 40 stones were removed after a follow-up period of 31 +/- 6 months. Oral ursodeoxycholic acid facilitates extraction of defiant bile duct stones. This treatment is an effective alternative to high-tech extraction methods for large biliary stones. PMID- 8365602 TI - Endoscopic treatment of Mirizzi's syndrome. AB - Electrohydraulic lithotripsy has been shown to be an effective non-surgical treatment for common bile duct and intrahepatic duct stones. This technique was applied via the endoscopic retrograde route in 14 patients (mean age, 70) with the Mirizzi syndrome, all of whom were at high risk for surgery. The procedure was performed under strict cholangioscopic guidance. Twelve patients had a single stone and two had multiple stones impacted in the cystic duct. Stone diameter was 1.5 cm in one patient, 2 to 3 cm in nine patients, and greater than 3 cm in four patients. Insertion of the babyscope and stone fragmentation were successful in all patients. Complete stone clearance required one session in 12 patients and two sessions in two patients (both with multiple stones). In one patient post procedural leakage of contrast medium from the cystic duct into the peritoneal cavity was noted. This was attributed to pressure necrosis induced by the impacted stone. The patient had an uneventful course of recovery, and leakage resolved with conservative management. Mortality was zero. Endoscopic treatment of the Mirizzi syndrome with electrohydraulic lithotripsy seems to be an effective and relatively safe alternative to surgery. PMID- 8365603 TI - Feeding tubes in endoscopic and clinical practice: the longer the better? AB - In an attempt to combine successful distal feeding tube positioning and a more prolonged stay without interfering with tube patency and feeding regimens, commercially available 105-cm polyurethane feeding tubes were compared with experimental tubes 125 cm and 145 cm long. The technique for endoscopic positioning at the bedside of the patient was standardized. Forty-five patients who required intraduodenal or intrajejunal enteral feeding in the intensive care unit were randomly assigned to one of the three tube-length groups. Even the 105 cm short feeding tubes were able to be introduced beyond the duodenojejunal junction, although insufficient tube length remained for tube fixation at the nose. The longer variants, however, were positioned significantly (p < 0.01) deeper in the intestine, with enough spare tube length for slack formation in the stomach and fixation at the nose. Tubes were electively removed in 29% of the patients. Irrespective of tube length, premature removal by the patient (in 36%) or by the nurse (in 11%) was rather high. Tube blockage was irremediable in 9%. Feeding tubes survived on average 10.6 days in all three tube-length groups, despite the fact that many drugs were administered by tube as well. The successful, easy, and fast endoscopic positioning of feeding tubes far into the intestine and at the patient's bedside may further expand the possibility for enteral feeding. Moreover, polyurethane materials are well tolerated, and increasing the tube length does not interfere with tube patency or feeding plans. PMID- 8365604 TI - Scalloped duodenal folds in childhood celiac disease. AB - Unlike the adult form, childhood celiac disease has not hitherto been associated with a particular endoscopic pattern. The upper gastrointestinal tracts of 46 children with various stages of celiac disease and of 27 children with conditions other than celiac disease were examined by an endoscopist unaware of the clinical details of the patients. The scalloped configuration of duodenal folds was shown to have a sensitivity of 88% and a specificity of 87% in the diagnosis of subtotal villus atrophy. Attention to this finding, described here for the first time in childhood celiac disease, may be helpful for the diagnosis of this condition. PMID- 8365605 TI - Artery weld strength after bipolar electrocoagulation is affected by electrolyte solutions around the artery. AB - We have recently shown that artery weld strength is significantly increased by increasing bipolar electrocoagulation time in fresh rabbit arteries, which had either 2 or 20 seconds of electrocoagulation under uniform conditions. In this study we investigated the effect of using either distilled water or physiologic saline around the artery during electrocoagulation in a total of 27 experiments, because it is the current practice to wash clot and liquid blood off bleeding ulcers with water. Fresh rabbit arteries were used, with a bipolar coagulation time of 2 seconds, with a constant weight of 500 gm applied to the head of the probe to standardize conditions. The bursting pressure of the coagulum was determined by cannulating the artery and increasing the pressure until the coagulum seal fractured. The artery weld strength was significantly lower when distilled water was used (median, 87.5 mm Hg; range, 10 to 225 mm Hg) compared with results when normal saline was used (median, 150 mm Hg; range, 100 to 850 mm Hg); by Mann-Whitney tests U = 42.5, Z = 2.36, and p = 0.018. These data suggest that more effective hemostasis of bleeding arteries may be achieved by not only more prolonged use of the diathermy probe, but also by using physiological saline as the washing solution instead of water, as is currently practiced. PMID- 8365606 TI - Pneumatic dilation of a sigmoid esophagus in achalasia using an overtube. PMID- 8365607 TI - A new approach to stenting a tight, angulated post-operative biliary stricture. PMID- 8365608 TI - The "stent through wire mesh technique" for complicated biliary strictures. PMID- 8365609 TI - Safety and efficacy of a new flexible video laparoscope in diagnostic laparoscopy. PMID- 8365610 TI - Use of a new cytology balloon for diagnosis of symptomatic esophageal disease in acquired immunodeficiency syndrome. PMID- 8365611 TI - Esophageal intramural pseudo-diverticulosis: endoscopic and radiologic correlation. PMID- 8365613 TI - Intermittent positional torsion of the gallbladder demonstrated on ERCP. PMID- 8365612 TI - Esophageal leiomyoblastoma: the role of endoscopic procedures in the pre operative diagnosis. PMID- 8365614 TI - Bile duct drainage with lavage by nasobiliary tube in a patient with mucin producing cystic pancreatic tumor. PMID- 8365616 TI - Massive intra-hepatic and extra-hepatic bile cast formation after cholecystectomy. PMID- 8365615 TI - Failure to deflate the balloon of replacement gastrostomy tubes. PMID- 8365617 TI - Percutaneous endoscopic gastrostomy for treatment of gas-bloat syndrome. PMID- 8365618 TI - Ulcerative jejunitis in refractory celiac disease: enteroscopic visualization. PMID- 8365619 TI - The Japanese experience with endoscopic ultrasonography in the staging of gastric cancer. AB - The Japanese experience with endoscopic ultrasonography in the staging of gastric cancer is reviewed and compared with Western results. Various graphic classifications for prediction of the depth of transmural penetration characterize the Japanese approach. Differentiation of early gastric cancers from advanced cancers has been emphasized, with the concordance rate of the ultrasonographic interpretation and the pathology exceeding 90%. When pre operative staging by the TNM system was attempted, results were similar to the reports from the West, with overall concordance rate for tumor depth of greater than 80%. The Japanese system of classification may be useful in differentiating advanced cancers from early gastric cancers with co-existing ulceration and fibrosis. The reliability of endoscopic ultrasonography in the pre-operative staging of gastric cancer in Japan is similar to that in the West. PMID- 8365620 TI - Is the small colorectal polyp clinically diminutive? PMID- 8365621 TI - Sphincter of Oddi manometry: how far is the leap of faith? PMID- 8365622 TI - Electronic networking: pass it on. PMID- 8365623 TI - Esophageal intubation over a guide wire. PMID- 8365624 TI - Balloon dilation of corrosive esophageal strictures. PMID- 8365625 TI - Removal of an embedded PEG bumper. PMID- 8365626 TI - A screw tip for cleaning endoscopes. PMID- 8365627 TI - Arterial bleeding from Billroth II anastomotic scars. PMID- 8365629 TI - Obstructed PEG tubes. PMID- 8365628 TI - Diagnosis of malignant bile duct obstruction using a Dormia basket. PMID- 8365630 TI - Per anus enteroscopic demonstration of a non-steroidal anti-inflammatory drug induced ileal stricture. PMID- 8365631 TI - Esophageal perforation during ERCP. PMID- 8365632 TI - Dieulafoy's lesion of the esophagus. PMID- 8365634 TI - Endoscopic ultrasound staging of rectal cancer. PMID- 8365633 TI - Endoscopic management of phytobezoars. PMID- 8365636 TI - Regulation of vascular smooth muscle contraction by extracellular Na+. AB - 1. The effects of extracellular Na+ removal on agonist-induced contraction of vascular smooth muscle in vitro are reviewed. 2. The effects of extracellular Na+ removal on contraction vary depending upon the agonist and vessel. 3. Factors that may influence the effects of extracellular Na+ removal on agonist-induced contraction include the compound substituted for Na+, time of tissue exposure to lowered extracellular Na+, concentration of extracellular Na+, agonist concentration, presence of the vascular endothelium and presence of basal tone. 4. The potential influence of these factors needs to be determined and minimized, in studies that investigate the role of extracellular Na+ in agonist-induced contraction. PMID- 8365635 TI - The inhibition of neurogenic inflammation. PMID- 8365637 TI - Comparative electrophysiological and mechanical actions of ATP-sensitive potassium channel openers in canine Purkinje fibers. AB - 1. Electrophysiological and mechanical effects of ATP-dependent potassium channel openers on canine Purkinje fibers were examined. 2. Cromakalim and pinacidil (0.3 10 microM) and nicorandil (0.3-1 mM) shortened the action potential duration (APD), and reduced the contractile force, in a concentration-dependent manner. Other action potential parameters were unaffected. The effects were reversible. 3. Effects of the openers were antagonized by tetraethylammonium (a non-specific potassium channel blocker) and more potently by glibenclamide (a blocker of ATP sensitive K+ channel). 4. The APD shortening and the negative inotropic effect induced by a switch of stimulation frequency (from 0.5 to 3 Hz) were potentiated by the openers. At high Ca2+ (5.4 and 10.8 mM), the effects of the openers on the APD and contractile force were unaffected. 5. In the spontaneously beating preparations, the openers hyperpolarized the maximum diastolic potential, and an arrest occurred. 6. Under the calcium overload condition, the K+ openers abolished a delayed after depolarization, and enhanced the depressed post-rest potentiation. 7. These results suggest that the K+ channel openers increase the K+ conductance and might decrease the cellular Ca2+ level in calcium overloading cells, and that nicorandil might also act directly ATP-sensitive K+ channels. PMID- 8365638 TI - Propionate regulates lymphocyte proliferation and metabolism. AB - 1. The effect of propionate on lymphocyte proliferation and metabolism was investigated. Lymphocytes obtained from human blood and rat mesenteric lymph nodes were utilized. 2. Propionate at concentrations of 0.04 and 1.0 mmol/l stimulated the amount of [3H]thymidine incorporated either in cultured human T lymphocytes or rat T and B lymphocytes. 3. Concentrations of propionate between 2 and 5 mmol/l caused a marked inhibition of lymphocyte proliferation. 4. This short-chain fatty acid was metabolized by these cells and produced succinate in significant amounts; however, its oxidation was low. 5. Propionate did not alter glucose, glutamine and pyruvate utilization and oxidation in incubated rat lymphocytes but increased the formation of lactate and aspartate. 6. In contrast, propionate inhibited by 50% the synthesis of lymphocyte lipid from [1-14C]acetate at concentrations of 0.5 and 1 mmol/l and reduced by half the incorporation of 3H2O into lipids at 1 and 5 mmol/l. 7. The results suggest that inhibition of lipid synthesis is a possible mechanism leading to reduction of lymphocytes proliferation. PMID- 8365639 TI - Relationship between negative inotropic and chronotropic effects of tocainide and five class I antiarrhythmic drugs in the coronary perfused guinea-pig heart. AB - 1. The relationship between the negative inotropic and chronotropic effects of tocainide and 5 other class I antiarrhythmic drugs was evaluated in Langendorff perfused guinea-pig hearts. 2. All 6 drugs reduced the contractile force (Fc) and the heart rate (HR) of spontaneously beating guinea-pig hearts in a dose dependent manner. The order of crude negative inotropic potency was: quinidine (Qui) = aprinidine (Apr) > mexiletine (Mex) > lidocaine (Lid) > disopyramide (Dis) > tocainide (Toc); and the order of negative chronotropic effect was: Apr > Qui > Mex > Dis > Lid > Toc. 3. The order of the negative inotropic potency relative to chronotropic effect (expressed as a ratio: ID50 for Fc/ID50 for HR) was Lid > Qui > Dis > Toc > Mex > Apr (n = 6). 4. For heart electrically stimulated at a constant rate, the order of crude negative inotropic potency was: Apr > Qui > Mex > Dis > Lid > Toc, and the order of negative inotropic potency (determined by the ratio: ID50 for Fc in driven heart/ID50 for spontaneously beating HR) was: Mex > Apr > Toc > Dis > Qui > Lid (n = 6). 5. There was a significant influence of negative chronotropic effect on the inotropic potency and the order was: Lid > Qui > Dis > Toc > Apr > Mex. The potency of various drugs is clinically useful in the choice of drugs when considering cardiac function and heart rate. PMID- 8365640 TI - Antiplatelet effect of pentoxifylline in human whole blood. AB - 1. Pentoxifylline inhibits platelet aggregation in whole blood more than in platelet-rich plasma. 2. An inhibition of the erythrocyte uptake of adenosine contributes to the antiaggregatory effect of pentoxifylline. PMID- 8365641 TI - Effect of ebrotidine on the synthesis and secretion of gastric sulfomucin. AB - 1. The effect of a new antiulcer agent, ebrotidine, on the synthesis and secretion of sulfomucin in gastric mucosa was investigated. Rat gastric mucosal segments were incubated in DMEM containing [3H]proline, [3H]glucosamine and [35S]Na2SO4 as markers for mucin synthesis, glycosylation and sulfation, in the presence of 0-150 microM ebrotidine. 2. The drug, while showing no discernible effect on the apomucin synthesis, evoked a dose-dependent increase in mucin glycosylation and sulfation, which at 100 microM ebrotidine, attained its maximum of 2.4 and 2.7-fold stimulation, respectively. 3. The analysis of mucin secretory responses revealed that ebrotidine caused a concentration-dependent enhancement in sulfomucin secretion which attained its maximum increase of 3.3-fold at 100 120 microM ebrotidine. Furthermore, the sulfomucin elaborated in the presence of ebrotidine exhibited a higher content of a large molecular-weight mucus glycoprotein form, the assembly of which is intimately associated with the sulfation event. 4. The results suggest that the ability of ebrotidine to enhance gastric sulfomucin synthesis and secretion may play an important role in the gastroprotective mechanism of action of this agent. PMID- 8365642 TI - Amplifying effect of serotonin on contractile responses in rat aorta and depletion of intracellular Ca-stores. AB - 1. Serotonin, 1 microM, induces a contractile response in isolated rat aorta in the presence or absence of extracellular Ca. 2. In Ca-free media, the fast phasic contraction is lower in magnitude and further addition of serotonin evokes no response. 3. Recovery of the contractile response in Ca-free medium is obtained by a 40 min incubation in Ca-containing solution. 4. In Ca, Mg-free medium, the response to serotonin is significantly higher than that obtained in the presence of Mg. 5. An amplifying effect of serotonin on the contractile responses induced by serotonin itself or by noradrenaline was observed in Ca-containing but not in Ca-free solution. PMID- 8365643 TI - Effect of short-term carbon tetrachloride administration on blood lactic acid levels. AB - 1. A short-term CCl4 administration was used in vivo as a model to produce a rise in lactic acid levels and to explain the probable interaction of CCl4 and lactic acid elevation with hepatic fibrogenesis. 2. A single dose of CCl4 produced an increase in lactic acid levels from 16.6 +/- 3.57 to 24.2 +/- 4.2 mg/dl. Three consecutive doses produced an elevation to 33.28 +/- 10.07 mg/dl, thus describing a direct relationship between lactic acid levels and CCl4 administration in a short-term fashion. 3. A morphological evaluation was performed to show hepatic changes caused by CCl4 administration. No clue of fibrogenesis was found. However, we conclude that an elevation in lactic acid exists, prior to cirrhosis. Therefore, chronic presence of lactic acid may lead to cirrhosis. PMID- 8365644 TI - Triphosphate, the key structure of the ATP molecule responsible for interaction with P2X-purinoceptors. AB - 1. A radioligand binding assay was carried out to explore the key structure in molecules of ATP and its analogues responsible for the binding to P2x purinoceptors. 2. It was found that adenosine, adenine and xanthine had no significant effect on [3H]alpha, beta-methylene ATP binding to membrane fractions prepared from rat urinary bladder, while pentasodium triphosphate and disodium pyrophosphate could effectively displace the binding. Sodium orthophosphate was shown to displace the binding only at much higher concentration. 3. Apart from ATP, several other nucleotides could also fully displace the specific binding, but with potencies lower than that of ATP. 4. The results indicate that the phosphate side chain in molecules of ATP and its analogues is the key structure responsible for the binding to P2x-purinoceptors. PMID- 8365645 TI - Elucidation of the rapid in vivo metabolism of arecoline. AB - 1. The metabolism of arecoline (ARE) was examined in homogenates of mouse blood, brain, kidney, and liver tissue. 2. Liver and kidney tissues exhibited the greatest rates of ARE metabolism. 3. The specific carboxylesterase inhibitor TOCP (tri-o-tolyl-phosphate) as well as ISO-OMPA (tetraisopropyl-pyrophosphoramide) completely blocked ARE metabolism in liver homogenate. 4. ISO-OMPA significantly inhibited ARE metabolism by purified porcine liver carboxylesterase. 5. The data suggest that carboxylesterase (EC 3.1.1.1) is primarily responsible for the metabolism of ARE in the mouse. PMID- 8365646 TI - Endothelial modulation of 5-hydroxytryptamine-induced contraction in goat cerebral arteries. AB - 1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10(-8) -3 x 10(-5)M) caused concentration-dependent contractions, with EC50 = 2.1 (1.9-2.5) x 10(-7) M and Emax = 60 +/- 2% of 50 mM KCl-induced contraction. 2. Mechanical removal of endothelium significantly increased the Emax (91 +/- 8%) and did not change the EC50 value of 5-HT-elicited contractions. 3. Incubation of unrubbed arteries with the irreversible inhibitor of EDRF, gossypol (10(-5) M), significantly increased the contractile response to 5-HT (Emax = 77 +/- 4%). 4. Incubation of unrubbed arteries with the competitive inhibitor of the NO synthesis, NG-nitro-L-arginine (L-NOARG) (10(-5) M), significantly enhanced the arterial response to 5-HT (Emax = 71 +/- 5%). The effects of L-NOARG were reversed by L-arginine (10(-4) M) but not by D-arginine (10(-4) M). 5. Pretreatment with the inhibitor of cyclooxygenase, indomethacin (10(-5) M), significantly increased the response of unrubbed arteries to 5-HT, with an Emax of 69 +/- 3%. 6. These results suggest that endothelium modulates the constrictor effect of 5-HT in goat cerebral arteries by producing both EDRF, probably NO, and prostacyclin. PMID- 8365647 TI - The ribosome-inactivating, antiproliferative and teratogenic activities and immunoreactivities of a protein from seeds of Luffa aegyptiaca (Cucurbitaceae). AB - 1. The protein isolated from Luffa aegyptiaca seeds was capable of inhibiting protein synthesis in a rabbit reticulocyte lysate system and [3H]thymidine uptake by mouse melanoma (B16) cells. 2. It also adversely affected the development of mouse embryos in culture. 3. In enzyme-linked immunosorbent assay it reacted with antisera raised against other ribosome-inactivating proteins. PMID- 8365648 TI - Characterization of muscarinic receptors on the isolated guinea pig ileum at pharmacologically low concentrations. AB - 1. Several selective and non-selective muscarinic agonists (McN-A-343, RS-86, arecoline, oxotremorine-M, pilocarpine, cis-dioxolane, and acetylcholine) were examined for relaxant activity in the isolated guinea-pig ileum at pharmacologically low concentrations. 2. The concentrations studied include: 1 x 10(-12) M, 3 x 10(-12) M, 1 x 10(-11) M, 3 x 10(-11) M and 1 x 10(-10) M. 3. None of the compounds exhibited relaxant activity in both the field and non-field stimulated ileum. 4. All of the above compounds exert muscarinic agonist activity in a concentration range of 1 x 10(-9) M to 1 x 10(-6) M (Williams et al., 1992). 5. Thus, in the isolated guinea-pig ileum, muscarinic agonists do not exert relaxant activity of the gastrointestinal tract at low concentrations. PMID- 8365649 TI - The effect of ephedrine isomers and their oxazolidines on locomotor activity in rats. AB - 1. The four stereoisomeric ephedrines and four oxazolidines formed by reaction of each ephedrine isomer with salicylaldehyde were tested for their ability to increase locomotor activity in rats. 2. All ephedrine isomers except ( )pseudoephedrine increased locomotor activity; the order of potency was ( )ephedrine > (+) pseudoephedrine > (+) ephedrine. 3. All oxazolidine derivatives increased locomotor activity except (-)pseudoephedrine oxazolidine. 4. The oxazolidines derived from (-) and (+) ephedrine were slightly more active than their parent drugs. (+) Pseudoephedrine oxazolidine was less active than its parent. 5. Half-lives of hydrolysis were measured for the oxazolidines in aqueous buffer, ephedrine oxazolidines hydrolyze faster than pseudoephedrine oxazolidines. PMID- 8365650 TI - The effects of tacrine and zacopride on the performance of adult rats in the working memory task. AB - 1. The present study investigated the effects of tacrine (an inhibitor of acetylcholinesterase) and zacopride (the antagonist of 5-HT3 receptors) on the performance of adult rats in a continuous operant delayed non-matching to position task assessing spatial working memory. 2. Adult rats had a decline in the percent correct responses at the longest delays (16 and 30 sec) in this task. Tacrine (1.0 mg/kg) or zacopride (0.0025, 0.05, 1.0 mg/kg) did not increase the percent correct responses at any time delays. The higher dose of tacrine reduced behavioural activity (e.g. the decreased number of trials completed and increased sample press latency) of rats during memory testing, and it slightly increased choice accuracy across all the delays. 3. The combination of zacopride (1.0 mg/kg) and tacrine (1.0 mg/kg) increased the percent correct responses at the shortest delays, but not at the longest delays. 4. These results indicate a non mnemonic improvement in the accuracy performance of rats, and they suggest that the effects of acute, systemic administrations of zacopride (which is thought to increase the release of acetylcholine) or/and tacrine (which inhibits the breakdown of acetylcholine) do not improve spatial working/short-term memory in rats. PMID- 8365651 TI - Nicotinic cholinergic influences in pancreatic secretion induced by intraduodenal alkaline and acid solutions in the rabbit. AB - 1. The effect of hexamethonium on the exocrine pancreatic response to intraduodenal acidification and alkalinization, and the secretin and VIP release after these stimuli, was studied. 2. The hydroelectrolyte secretion after hydrochloric acid and sodium carbonate perfusion was reduced by hexamethonium treated (322 +/- 44% of maximum response in flow rate to sodium carbonate perfusion in untreated animals vs 140 +/- 12% in pretreated animals, and 252 +/- 19% of maximum response in flow rate to HCl in untreated animals vs 166 +/- 11% in pretreated animals). 3. However, hexamethonium has no effect on secretin plasma levels after either intraduodenal acidification or alkalinization. 4. On the contrary, the ganglion blocker significantly (P < 0.01) reduced plasma VIP levels in response to intraduodenal HCl (maximum response 320 +/- 74% in untreated vs 184 +/- 44% in hexamethonium-treated animals). 5. Plasma VIP levels showed a similar increase in both untreated (maximum response: 151 +/- 12%) and ganglion blocked animals (170 +/- 26%) in response to sodium carbonate. 6. These data suggest the existence of complex neural mechanisms in the exocrine pancreatic response to intraduodenal stimuli, these mechanisms being different depending on the intraduodenal stimulus. PMID- 8365652 TI - Ketorolac tromethamine: an experimental study of its analgesic effects in the rat. AB - 1. The formalin test and R-III nociceptive electromyographic reflex were used to determine the origin of analgesia induced by ketorolac tromethamine (KT) in rats. 2. The effects of KT and morphine were compared after i.v. administration. 3. Mepacrine and indomethacin were associated to KT to determine if prostaglandins are involved in the central action of KT. 4. In both tests KT had a poor analgesic effect without dose-response relationships. 5. A central component is involved in the analgesia produced by KT, but neither prostaglandins nor opioid receptors seem to mediate this effect. PMID- 8365653 TI - Reciprocal modulation of the binding of angiotensin agonists and antagonists to angiotensin receptors in smooth muscle. AB - 1. Direct ligand binding studies have shown that the agonist 125I-[Sar1]Ang II and the antagonist 125I-[Sar1Ile8]Ang II bind to bovine uterus smooth muscle membranes in a time-dependent, reversible and saturable manner; both ligands had the same number of high affinity sites. 2. [Sar1Ile8]Ang II inhibited the binding of 125I-[Sar1]Ang II in a non-competitive manner by decreasing the number of high affinity sites without changing the binding affinity of the radioligand. 3. [Sar1]Ang II also inhibited the binding of 125I-[Sar1Ile8]Ang II in a non competitive manner. 4. Dissociation of both radioligands from their receptor sites was fast enough that pseudo irreversible occupancy of the binding sites could not account for the observed non-competitive inhibition. 5. Displacement studies using 125I-[Sar1Ile8]Ang II as the radioligand provided evidence for the existence of two binding sites when the displacing ligand was [Sar1]Ang II but not when the displacing ligand was [Sar1Ile8]Ang II. 6. GTPS gamma S had no discernible effect on the binding of either 125I-[Sar1]Ang II or 125I [Sar1Ile8]Ang II to bovine uterine membranes. 7. The present findings are consistent with an allosteric mechanism of antagonism for [Sar1Ile8]Ang II. The data are also consistent with a mechanism wherein agonist and antagonist ligands occupy different binding modes at the same receptor site and induce long-term conformational changes in the receptor which are idiosyncratic with respect to the nature of the ligand. An emerging relationship between the actions of angiotensin peptides and non-peptide mimetics of angiotensin is presented. PMID- 8365654 TI - Role of calcium in mediating the biphasic contraction of the rabbit urinary bladder. AB - 1. The response of the urinary bladder to field stimulation is biphasic in nature consisting of an initial phasic contraction followed by a prolonged tonic phase which lasts for the duration of the stimulation. 2. The phasic response is mediated by the release of neurohumoral transmitters, primarily acetylcholine (via muscarinic receptor stimulation) and ATP (via purinergic receptor stimulation). The tonic component is mediated entirely via muscarinic receptor stimulation. 3. The present study investigates the dependence on extracellular calcium of the phasic and tonic contractile responses to field stimulation, bethanechol, and ATP. The results can be summarized as follows: 4. Field stimulation (2 and 32 Hz) and bethanechol evoke a biphasic contractile response whereas ATP evokes only a phasic response. 5. There were no significant effects of either calcium channel blockers or calcium fee EGTA medium on either spontaneous contraction or basal tension of muscle strips. 6. The calcium channel antagonists diltiazem and verapamil inhibited both the phasic and tonic responses induced by field stimulation (both 2 and 32 Hz) in a dose dependent manner. 7. For both 2 and 32 Hz stimulation, the ED50 s for the inhibition of the tonic phases of the responses to field stimulation were significantly lower than the ED50s for the inhibition of the phasic responses. 8. The tonic phase of the responses to field stimulation were inhibited to a significantly greater degree than the phasic responses by incubation in calcium-free medium containing EGTA. 9. Both the phasic and tonic components of the response to bethanechol stimulation were inhibited equally, and followed a similar time course as the tonic component of field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365655 TI - The role of endothelial cells on the alterations in vascular reactivity induced by insulin-dependent diabetes mellitus: effects of insulin treatment. AB - 1. In this study, the maximal contractile responses to noradrenaline (NA) were significantly increased but pD2 values (sensitivity) were not significantly altered in aortas with endothelium from insulin-dependent (ID)-diabetic rats when compared to their controls. 2. Removal of the endothelium resulted in a significant increase in the maximum response of control and ID-diabetic aortas and also loss of the difference in maximum contractile response to NA between ID diabetic aortas and their corresponding controls. 3. Endothelium-dependent relaxation stimulated by acetylcholine (ACh), methacholine, histamine, ATP and insulin, in aortic rings precontracted with NA were significantly attenuated but unchanged by A23187 in ID-diabetic vessels relative to controls. 4. Relaxations produced by sodium nitroprusside (SNP) in ID-diabetic aortas were similar to those in control vessels. 5. The sensitivity of ID-diabetic aortas to relaxant substances were not changed when compared with controls. 6. These results demonstrate that ID-diabetes-induced specific changes in vascular reactivity and endothelial cells have an important role on the maintenance of vascular tonus. This feature may be responsible for the major complications of diabetes such as macroangiopathy, vasospasm and high blood pressure in late stage of the disease. PMID- 8365656 TI - Noradrenergic-GABAergic interaction in anterior hypothalamus from normotensive and sinoaortic denervated rats. AB - 1. GABA content is decreased in anterior hypothalamus and medulla oblongata of hypertensive rats by sinoaortic denervation (SAD) when compared to control animals which underwent a sham-operation (sham). 2. Lesion of noradrenergic pathways by 6-hydroxydopamine (6-OHDA), intracerebroventricularly administered, induced depletion of noradrenergic content in frontal cortex, anterior and posterior hypothalamus in both SAD and sham-operated rats. 3. As a consequence of this noradrenergic depletion there was an increase of GABA content in anterior hypothalamus only, from sham- and SAD-operated animals, without changes in other areas. 4. There is a noradrenergic-GABAergic interaction in the anterior hypothalamus of normotensive rats which is not impaired in hypertensive rats by sinoaortic denervation. PMID- 8365657 TI - Evolution of the mitochondrial ATPase 6 gene in Drosophila: unusually high level of polymorphism in D. melanogaster. AB - We have determined 1990 bp mitochondrial DNA sequence which extends from 3' end of the cytochrome oxidase subunit I (COI) gene to 5' end of the COIII gene from two sibling species of Drosophila, D. simulans and D. mauritiana. Analyses of the sequences and part of the NADH dehydrogenase subunit 2 gene and the COI gene together with those from D. melanogaster and D. yakuba revealed that amino-acid substitution rate of the ATPase 6 gene seems to be higher in some strains of D. melanogaster than in the other species. High level of amino-acid polymorphism in this gene was observed in D. melanogaster. Synonymous substitution rate is relatively constant in all the genes examined, suggesting that mutation rate is not higher in the ATPase 6 gene of D. melanogaster. The amino-acid substitutions found specifically in D. melanogaster are at the sites which are not conserved among mammals, yeast and E. coli. These sites of the ATPase 6 gene might lose the selective constraint in D. melanogaster, and the amino-acid substitutions can be explained by neutral mutations and random genetic drift. PMID- 8365658 TI - Directional selection and the evolution of sex and recombination. AB - Models of the evolutionary advantages of sex and genetic recombination due to directional selection on a quantitative trait are analysed. The models assume that the trait is controlled by many additive genes. A nor-optimal selection function is used, in which the optimum either moves steadily in one direction, follows an autocorrelated linear Markov process or a random walk, or varies cyclically. The consequences for population mean fitness of a reduction in genetic variance, due to a shift from sexual to asexual reproduction are examined. It is shown that a large reduction in mean fitness can result from such a shift in the case of a steadily moving optimum, under light conditions. The conditions are much more stringent with a cyclical or randomly varying environment, especially if the autocorrelation for a random environment is small. The conditions for spread of a rare modifier affecting the rate of genetic recombination are also examined, and the strength of selection on such a modifier determined. Again, the case of a steadily moving optimum is most favourable for the evolution of increased recombination. The selection pressure on a recombination modifier when a trait is subject to strong truncation selection is calculated, and shown to be large enough to account for observed increases in recombination associated with artificial selection. Theoretical and empirical evidence relevant to evaluating the importance of this model for the evolution of sex and recombination is discussed. PMID- 8365660 TI - Beware: the Beijing flu is coming. Immunization--with new Medicare coverage- provides some protection. PMID- 8365659 TI - The advance of Muller's ratchet in a haploid asexual population: approximate solutions based on diffusion theory. AB - Asexual populations experiencing random genetic drift can accumulate an increasing number of deleterious mutations, a process called Muller's ratchet. We present here diffusion approximations for the rate at which Muller's ratchet advances in asexual haploid populations. The most important parameter of this process is n0 = N e-U/s, where N is population size, U the genomic mutation rate and s the selection coefficient. In a very large population, n0 is the equilibrium size of the mutation-free class. We examined the case n0 > 1 and developed one approximation for intermediate values of N and s and one for large values of N and s. For intermediate values, the expected time at which the ratchet advances increases linearly with n0. For large values, the time increases in a more or less exponential fashion with n0. In addition to n0, s is also an important determinant of the speed of the ratchet. If N and s are intermediate and n0 is fixed, we find that increasing s accelerates the ratchet. In contrast, for a given n0, but large N and s, increasing s slows the ratchet. Except when s is small, results based on our approximations fit well those from computer simulations. PMID- 8365661 TI - Preparing for surgery: this practical workup pinpoints preoperative dangers. AB - Older patients undergo 20 to 40% of surgical procedures and account for 50% of surgical emergencies. Your presurgical workup can pinpoint potential cardiac, pulmonary, or metabolic problems that could endanger your patient in the operating room. Not everyone needs an extensive cardiac workup. To determine who does, you can use the Goldman criteria to predict the risk for postoperative cardiac complications. Preoperative test selection is based on these predicted risks and on information from the patient history and physical exam. Medication adjustments and discharge planning are important considerations as well. PMID- 8365662 TI - Adult vaccinations: protecting your patients from avoidable illness. AB - Influenza vaccine is recommended each year for any adult at high risk for lower respiratory tract complications and death. Also consider immunizing household members of high-risk patients. Those who are susceptible to influenza are also at risk for pneumococcal disease; consider revaccination more than 6 years after the first dose for those at the highest risk of declining antibody levels. Any adult patient whose tetanus immunization status is uncertain should be considered unvaccinated and receive a full three-dose primary series of Td. In the United States, hepatitis B is usually a disease of lifestyle or profession. Rabies vaccine is indicated for your older patients who hunt, trap, explore caves, or travel to endemic areas. PMID- 8365663 TI - Eyelid disorders: recognizing pathologic changes in the older patient. AB - The eyelids provide a vital function in protecting and cleansing the eye but are also the source of numerous disorders and complaints in your older patients. Clinically, the most important of these problems are suspicious lid lesions that may harbor malignancy, neurologic disorders, and structural malpositions that cause poor lid function and may damage the globe. Many of these disorders require prompt evaluation and often referral to an ophthalmologist for surgical management. Less serious problems such as blepharitis can often be treated in the primary care office setting. PMID- 8365664 TI - When your older patient can't sleep: how to put insomnia to rest. AB - Sleep disorders are common in midlife and older adults, coinciding with encephalographic changes in sleep patterns, stressful life events, and chronic diseases of aging. Differential diagnosis includes respiratory abnormalities (including obstructive sleep apnea), leg cramps, nocturia, ulcer-related pain, medication use, depression, and anxiety. Sedative-hypnotic agents may be appropriate for selected patients, with short-acting substances preferred in all cases. Dosage and dosing schedules should be discussed with the patient to ensure compliance and to avoid possible misuse of these agents. PMID- 8365665 TI - The biology of aging: looking to defuse the genetic time bomb. AB - Each cell is functionally restricted by differentiation, which determines its complement of active and inactive genes. Various diseases then become manifest in each cell, depending on these specific gene combinations. Neoplasia, for example, is due to a multistep series of genetic mutations. It is common in continuous replicators such as bronchial epithelium, colon, and marrow but rare in intermittent replicators such as endothelial and smooth muscle cells. In contrast, these latter cell types are centrally involved in degenerative phenomena such as atherosclerosis. However, in both continuous and intermittent replicators, reduction of gratuitous cell turnover will be of great benefit. The nonreplicating adult neuron almost never undergoes tumorigenesis compared with glial cells but gives rise to a variety of age-related degenerative diseases such as Alzheimer's or Parkinson's disease. In the nonreplicating neuron, therefore, it is imperative that we promote strategies to preserve cell viability by minimizing oxidative damage. Natural antioxidants such as vitamin C and E and beta carotene, as well as an optimal caloric and protein intake, should be cornerstones of treatment and prevention for the aging patient. A place for pharmacologic intervention is also likely soon. Current research should soon identify the precise mechanisms responsible for programmed cellular senescence and oxidative cellular damage so as to illuminate additional means of rational treatment, and perhaps more importantly, prevention. PMID- 8365666 TI - Close linkage of the gene for Werner's syndrome to ANK1 and D8S87 on the short arm of chromosome 8. AB - Werner's syndrome (WRN) is a rare autosomal recessive disorder characterized by the appearance of features of premature aging in a young adult. Skin fibroblasts from WRN patient demonstrate slow growth, reduced life span in vitro and mutator phenotype. The genetic defect in WRN is unknown. We have studied 23 WRN patients mainly from first or second cousin marriage and have applied homozygosity mapping to search for the WRN locus. A peak lod score of 5.58 at a recombination fraction of 0.03 was obtained with D8S87. We confirmed that the WRN locus was located on the short arm of chromosome 8, 8p11.2-p12. PMID- 8365667 TI - A seroimmunological analysis of Down syndrome. AB - Down syndrome (DS) was studied in terms of immunological function and serological aspects. It was found that antibody levels against rubella and pertussis in the sera from 36 institutionalized DS patients were comparable with those of healthy controls while low antibody levels were detected against mumps and measles. Six tumor markers were also assayed in the serum from DS patients and the serum concentration of alpha-1-acid glycoprotein (alpha 1-AGP) and immunosuppressive acidic protein, an analogous glycoprotein of alpha 1-AGP, were significantly higher than those of the control group. Multivariate discriminant function was constructed based on the concentration of tumor markers. The function could discriminate between the two groups at a sensitivity of 92.3%. Flow-cytometrical analysis has revealed that helper T level of DS patients' sera was lower than that of the control group. PMID- 8365669 TI - Comparison of the age- and tumor-associated changes in the c-myc gene methylation in mouse liver. AB - Study of DNA methylation of the c-myc gene in liver tumors of BCF1 mice treated with various agents revealed frequent alteration from that in normal liver. The alteration, however, was complex and showed either an increase or a decrease of methylation to various degrees. On the other hand, the tumors obtained from middle-aged C3H/He mice, which develop liver tumors spontaneously at a high incidence rate starting in middle age, showed predominantly increases of methylation in the c-myc gene, while the large tumors found in older mice revealed decreases. The normal part of the liver showed a slight gradual age dependent increase. These suggest that hypermethylation of the c-myc gene is common to aging and early tumor development in liver. Thus the alteration of DNA methylation seems to be a good clue to investigate why the tumor incidence rate increases rapidly as individuals grow older. PMID- 8365668 TI - Amyloid precursor protein is found in lysosomes. AB - The major component of Alzheimer's disease amyloid is a small polypeptide referred as the amyloid beta protein, which is derived from a larger precursor, amyloid precursor protein (APP). Cell fractionation and immunological studies on the APP molecule indicate that APP is localized either in the neuron and astrocyte and that the molecule is recovered from lysosomal fraction. PMID- 8365671 TI - [Origin of Roman medical criticism and its reception in Rome]. AB - Our view of Cato's (234-149 B.C.) attitude towards Greek medicine and Greek doctors has been influenced by the elder Pliny (23-79 A.D.). Evidence is shown which suggests that Cato's rejection of Greek medicine did not prevent him from using the help of Greek physicians. PMID- 8365670 TI - Purification of a trypsin-type protease from human umbilical vein endothelial cells which is highly sensitive to the Kunitz inhibitor domain peptide of Alzheimer's disease amyloid protein precursor. AB - A trypsin-type protease was purified to enzymatic homogeneity from human umbilical vein endothelial cells by sequential affinity chromatographies. The enzyme specifically hydrolyzed dibasic substrates with leucine at the P3 positions, but scarcely hydrolyzed the other substrates tested. The enzyme was strongly inhibited by the Kunitz inhibitor domain peptide of Alzheimer's disease amyloid protein precursor (Ki value, 0.35 nM) and by the microbial inhibitors leupeptin and anti-pain. These results, together with a previous finding of a significant increase in the expression of Alzheimer's amyloid protein precursors (beta APPs) with the Kunitz inhibitor domain in Alzheimer's disease, suggest that the activity of the trypsin-type protease is suppressed by an increase of beta APPs with inhibitor activity in Alzheimer's disease, resulting in aberrant intracellular protein catabolism including degradation of beta APPs and beta protein deposition. PMID- 8365672 TI - [Jung to Freud 1905: a report on Sabina Spielrein]. AB - A recently discovered letter, dated September 25, 1905, proves that Jung's first attempt to get in contact with Freud had taken place earlier than it was assumed on the basis of their published correspondence. The letter contains a brief case history of Sabina Spielrein's disease. It was addressed to Freud and handed over to Sabina Spielrein's mother who intended to remove her daughter from Jung with whom the girl had fallen in love. However, the letter was never passed on to Freud. PMID- 8365673 TI - [Hard drugs--yesterday and today. A cultural historical essay]. AB - This article tries to examine the current problems of drug consumption from different points of view. Some major historical, sociological, psychological, and economical aspects are dealt with in order to show the enormous complexity of the subject matter. An attempt is also made to make clear that all approaches suggesting "easy answers" to the drug problems are bound to fail and that the desire to build up a drug-free society has always been a complete illusion. PMID- 8365674 TI - [In awe of creation: "Tota substantia", "calidum innatum", "generatio spontanea" and atomic form teachings of Daniel Sennert]. AB - A thorough study of the system of a philosophy of nature, elaborated by the well known German physician Daniel Sennert (1572-1637). At the beginning of the modern era, Sennert developed a new and very complex concept of the relations between matter and the guiding principle active in it, the Aristotelian form. PMID- 8365675 TI - [In memory of Paul Bert (1833-1886) and the development of high altitude physiology in Switzerland]. AB - It is the merit of Paul Bert to have assigned as an important task to experimental physiology the investigation of mountain sickness, of immediate accommodation of the organism to high altitude, and of its long-term acclimatation. In his "Pression Barometrique" of 1878, he established the foundations of high-altitude physiology. In particular, he formulated the "law of partial pressure", the partial pressure of the atmospheric gases alone being responsible for their action on the organism. Paul Bert's historic role, for a long time nearly forgotten, has been recalled to memory by the Swiss medical historians E.H. Ackerknecht and N. Mani. Bert's line of investigation has been followed especially by Angelo Mosso of Turin and, more recently, by F. Verzar, A. von Muralt, A. Fleisch and other Swiss physiologists. PMID- 8365676 TI - The mystery of Louis Verrey (1854-1916). AB - In 1888, Louis Verrey, a Swiss ophthalmologist, stated emphatically that there is a "centre for the chromatic sense" in the human brain and that it is located in the lingual and fusiform gyri. He did not, however, consider the "colour centre" to be a separate area but a large sub-division of the primary visual cortex. His evidence was quickly dismissed and forgotten. It was not to be taken seriously again until after the experimental discovery of functional specialization in the monkey brain. This paper considers why it is that Verrey did not consider the "colour centre" to be a separate cortical area, distinct from the primary visual cortex, why his evidence was so quickly and effectively dismissed, and why it is that Verrey did not pursue the logic of his findings. PMID- 8365677 TI - [Effect of melatonin on the function of the pituitary-gonadal axis in food restriction states]. AB - The effects of melatonin (25 micrograms s.c. daily in the late afternoon during ten days) on the ovarian morphometry and the gonadotropin secretion were investigated in food-restricted and fed ad libitum rats. It was found that in food-restricted rats melatonin produced the significant decrease of the surface area of the whole ovary and of zona granulosa. Moreover melatonin treatment of food-restricted rats resulted in significant decrease of the relative areas of graafian follicles and zona granulosa estimated in relation to the whole ovary cross-section surface area. On the other hand melatonin did not produced significant alterations of the morphometric indices of the ovary in fed ad libitum rats. Melatonin administration was found to inhibit the effects of gonadotropin release in food-restricted but not in normally fed rats. These findings suggest that food restriction sensitizes the pituitary ovarian axis to antigonadotropic melatonin action. PMID- 8365678 TI - [The course of sexual development in girls with diabetes type I in view of ultrasonographic examinations]. AB - The gynecologic a ultrasonographic examinations in 34 insulin--dependent diabetic girls aged from 1-9 y, were performed. Diabetes duration oscillated between 1-9 y. The obtained results showed that the dynamics of sexual maturation of this girls was independent of theirs calendar age, but was conditioned by the time of obtained sexual development. The right metabolic balance of diabetes stipulates regular course of sexual maturation. PMID- 8365679 TI - [Significance of assay of FSH and LH in anovulatory cycles of girls primary and secondary amenorrhea]. PMID- 8365680 TI - [Analysis of cause and test treatment of amenorrhea in teenagers]. AB - The population of 49 young, secondary amenorrheic women aged 17 to 20 was divided according to reaction on i.m. injection of progesterone in oil. The positive category was subdivided into I--polycystic ovarian disease with elevated serum LH and II--hypothalamic-pituitary dysfunction (HPD) with normal (or decreased) level of LH. The negative category consists of subgroup, III--hypothalamic-pituitary failure (HPF) with normal or low serum FSH and IV--ovarian failure with elevated level of FSH (two patients were noted). The bleeding response was obtain in two third of the patients, and also two third of them ovulated after clomiphene citrate treatment, including all six women with POC. The ovulatory response in patients with hypothalamic pituitary failure was noted in more than 40%. The low concentration of serum FSH (below 5 mU/ml) was more frequent in HPF (57%) in comparison with HPD (48%). The resistance to clomiphene citrate treatment was correspondingly 62.5% and 70%. When the ovulation occurred no difference in the regular function of corpus luteum in POC, HPD and HPF patients was noted. PMID- 8365681 TI - [Primary dysmenorrhea in teenagers]. AB - Authors demonstrate 21 cases with primary dysmenorrhoea at girls aged 14-17 years, which were observed between 1989-1992 and present way of treatment. In their opinion administration of nonsteroid, antiphlogistic medicaments and the spasmolytics is the most effective method. PMID- 8365682 TI - [Chromosome loss in metaphase of peripheral blood lymphocytes in patients with Turner's syndrome before treatment and at the time of substitution therapy]. AB - Chromosome loss in metaphases of 72 hours human peripheral blood lymphocyte cultures, at the Turner syndrome (45,X, and 46,X,izo(Xq),) patients is three times higher than in lymphocyte cultures of healthy women. Hormonal therapy decreases frequency of chromosome loss. PMID- 8365683 TI - [Clinical examinations, chromosomal and molecular DNA in patients with Swyer syndrome]. AB - Two girls with Swyer syndrome (SS) were described. Diagnosis was established according to clinical data and ultrasound, laparoscope, histopathological, hormonal and cytogenetical examinations. One presents diagnostic possibilities followed advanced methods in genetics. The GTG and RBG high resolution bounding technique and replication analysis of short arms (Xp and Yp) were employed. Normal structure of end segments of X and Y chromosomes was mentioned. Molecular DNA analysis by polymerase chain reaction (PCR) did not find any mutation in SRY gene. Normal structure of this gene does not exclude possibility of SS existence. Our data implicates on the other mechanism of these disturbances. PMID- 8365684 TI - [Diagnosis of sex differential disorders treatment in teenagers]. AB - Inter-sexuality is diagnosed in the age between 8-19 years in 58.5% among all 253 individuals with the signs of hermaphrodite. The diagnosis requires clinical, hormonal, cytogenetic and sometimes histopathological investigations. At the youthful patients with signs of hermaphrodite there are confirmed in 66.3% different kinds of gonadal dysgenesis, in 15.5% androgen insensitivity syndrome, in 12.2% congenital adrenal hyperplasia, in 3.4% transsexualism and in 1.3% adrenal virilizing tumours. To call attention to the specific and different treatment of every kind of hermaphrodite it is necessary a very early proper diagnosis of the disease. PMID- 8365685 TI - [Differential diagnosis of hirsutism in girls between 15-19 years old]. AB - On the basis of clinical and hormonal investigations of 58 girls with hirsutism aged between 15-19 years there were confirmed congenital adrenal hyperplasia in 3.4%, late onset adrenal hyperplasia in 24.1% and polycystic ovary syndrome in 72.4%. The proper diagnosis were established above all on endocrinological investigations especially on determinations of 17- ketosteroids, of DHEA, of 17 OH-corticoids in urine and RIA of total and free testosterone in blood. PMID- 8365686 TI - [Activity of b-endorphin in patients with premature ovarian failure]. AB - Examination of B-endorphin blood serum levels of 27 girls and young women with premature ovarian function depression was performed Patients were not pregnant before. The 54 young, regularly menstruating, healthy women composed the control group, who were divided into two groups according to the menstrual phase. Levels of B-endorphin were lower in examined group than in control one. High levels of B endorphin were found at the patients with secondary diagnosed insensitive ovary syndrome. This fact suggest that examination of B-endorphin levels can be useful for clinical differentiation of insensitive ovary syndrome and premature ovarian function depression. PMID- 8365687 TI - Antithrombotic effect of argatroban on the pial vessels of the rat: a study with He-Ne laser-induced thrombus formation. AB - The antithrombotic effect of the synthetic thrombin inhibitor (2R,4R)-4-methyl-1 [N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2 piperidinecarboxylic acid monohydrate (argatroban) was investigated in cerebral vessels of the rat. An occlusive thrombus was formed in pial vessels using a He Ne laser in a closed cranial window technique. Argatroban retarded the formation of thrombi in a dose-dependent manner. The antithrombotic effect of a single intravenous dose of argatroban at 0.5 mg/kg was diminished after 30 min in arterioles and after 50 min in venules, respectively. The antithrombotic activity was maintained, however, by continuous intravenous infusion (2 mg/kg/h). PMID- 8365688 TI - Characterization of a novel activation-specific antiplatelet monoclonal antibody. AB - We developed a murine monoclonal antibody (KmT-50) which binds to a protein expressed on the surface of human platelets after activation. KmT-50 is an immunoglobulin G1 monoclonal antibody that recognizes a 50-kD antigen localized in intracellular organelles and the open canalicular system of unstimulated platelets. After platelets were stimulated, the antigen was secreted via the surface-connected canalicular system and exposed on the platelet membrane. KmT-50 bound not only to human platelets, but also to rabbit and monkey platelets. This new antibody may be useful for experimental studies on thrombosis and hemostasis. PMID- 8365689 TI - Controlled vitamin K content diet for improving the management of poorly controlled anticoagulated patients: a clinical practice proposal. AB - The aim of our study was to investigate the effect of a diet with a known vitamin K content on the monitor test for oral anticoagulant therapy. We studied 10 poorly controlled patients (7 women and 3 men, mean age 48 +/- 15 years) in therapy with acenocoumarol for at least 1 year. Another group of 10 poorly controlled patients was considered as a control group. After a baseline period, during which a free diet was allowed, patients were administered a diet with a controlled vitamin K content; in the same period, control subjects were not subjected to any dietary restriction. Thrombotest (Nyegaard, Oslo) was employed for monitoring oral anticoagulant therapy, with a therapeutic range between 2.3 and 4.8 INR. We found a significant difference by thrombotest between the percentages within the therapeutic range obtained before and during dietary treatment (p = 0.0001). The difference in percentages was -0.31 and the 95% CI, of the difference ranged from -0.45 to -0.17. No significant difference was shown in the control group in the same periods. Our data suggest that a diet with a controlled vitamin K content is effective in increasing the percentage of tests within the therapeutic range in patients with poorly controlled anticoagulation. PMID- 8365690 TI - Concentrations of phenprocoumon in serum and serum water determined by high performance liquid chromatography in patients on oral anticoagulant therapy. AB - Two convenient high-performance liquid chromatography procedures are proposed for the determination of phenprocoumon (Marcumar) in serum (S-PPC) and its unbound fraction in serum water (SW-PPC). S-PPC and SW-PPC were determined in samples from 53 patients undergoing oral anticoagulant therapy who were within the therapeutic interval of the thrombotest. S-PPC concentrations ranged from 0.6 to 5.0 mg/l, SW-PPC from 1.4 to 21.1 micrograms/l. A linear correlation (r = 0.714) was found between S-PPC and SW-PPC concentrations in the patient samples, the mean free fraction being 0.30%. S-PPC and SW-PPC concentrations were intra individually stable during therapy. A linear correlation (r = 0.710) was observed between S-PPC concentrations and dosage. PMID- 8365691 TI - Fibrinogen and fibrin derivatives in traumatized patients: relation to injury severity and posttraumatic pulmonary dysfunction. AB - In a prospective study including 30 traumatized patients, levels of fibrinogen, fibrinopeptide A (FpA), fibrin monomers (FM) and fibrin degradation products (FbDP) were measured on admission and on days 1, 2, 3 and 7 after the incident. High levels of FpA, FM and FbDP were observed immediately after the trauma. Fibrinogen levels increased during the first 7 posttraumatic days whereas FpA and FM decreased. FbDP was significantly higher on day 7 than on day 3. All variables were to some extent correlated to the injury severity score. FbDP were significantly lower on the day after admission in 4 patients who developed pulmonary dysfunction compared with patients without this complication. PMID- 8365692 TI - Cathepsin G inactivates human protein S in vitro. AB - Human polymorphonuclear leukocyte cathepsin G was used in vitro to digest human protein S. While clotting assays indicated that the proteinase induced a rapid decrease in activity, polyacrylamide gel electrophoresis-sodium dodecyl sulphate indicated the removal of a peptide of low molecular mass product protein S (des 1 40). The loss in activity was the result of cathepsin G cleaving position Phe40 Tyr41 and removing the calcium-binding region. Calcium ions almost totally protected the cofactor from the action of cathepsin G in vitro. PMID- 8365694 TI - Elimination of plasmid pKM101 from Salmonella typhimurium by monoammonium salts. AB - The frequency of elimination of plasmid pKM101 from Salmonella typhimurium TA92 exposed to the action of 1-alkyl-1-ethylpiperidinium bromides and N-alkyl-N-[5 (benzoyloxy)-3-oxapentyl]-N,N-dimethylammonium bromides was non-linear in the homologous series. Change in the length of the alkyl chain markedly affected the elimination properties of the piperidine derivatives but had no effect on the elimination of benzoyl derivatives. Piperidines exhibited a weaker elimination capacity than the benzoyl derivatives. The most potent eliminator was the octylbenzoyl derivative, which causes the elimination of the plasmid in 80-85% cells. PMID- 8365695 TI - Synthesis and fungitoxicity of some pyrimidine derivatives. AB - A series of 12 pyrimidine derivatives were prepared and tested in vitro against growth, sporulation and nucleic acid content of Fusarium oxysporum f. sp. lycopersici and Helminthosporium oryzae. Introduction of a thiazole ring together with two aryl groups into 2-aminopyrimidine brought about drastic toxicity for both fungi. Pyrimidine derivatives with aryl groups alone were less toxic. Nitro groups were found to enhance the toxicity of the pyrimidine derivatives especially when substituted in the ortho-position of the aryl groups. Inhibition of nucleic acid synthesis of both fungi was attributed mainly to the presence of the thiazole ring. PMID- 8365693 TI - Characterization of two "Metabacterium" sp. from the gut of rodents. 2. Heteroxenic cultivation and proof of dipicolinic acid in "M. polyspora". AB - The vegetative cell of "Metabacterium polyspora" is "cucumber-shaped", about 21 x 5.7 microns, Gram-negative. Cylindrical endospores are best stained by Rakette and Ziehl-Neelsen staining. The bacterium reproduces by sporulation (2 to 8 endospores per cell) and by binary fission. Lateral, bow-like "hatching" of the endospores was seen. About 52% of guinea pigs harbor 5 x 10(6), 36% below 2 x 10(6) and 1% more than 1 x 10(8) "M. polyspora" in 1 g of caecal content. Dipicolinic acid was demonstrated using HPLC in the caecum homogenate from a guinea pig. The amount of it was proportional to the number of spores. Cultivation under strict anaerobic conditions did not succeed. It was possible to cultivate this giant endosymbiont in vitro in a heteroxenic culture incubated in a 5% CO2 atmosphere using liquid medium supplemented with cell-free filtrate of the caecum. The caecum filtrate containing undefined growth factor(s) is necessary for long-term culture. The replication rate was low. These findings suggest that the giant endosymbiont "M. polyspora" is a spore-forming prokaryote without the attributes of a strict anaerobe. PMID- 8365696 TI - Effect of alkyldimethylamine oxides on anaerobic sporulating bacteria of genus Clostridium. AB - Antibacterial activity of alkyldimethylamine oxides and Iodaminox was determined in vitro in 11 strains of clostridia. The most efficient was (1 methyldodecyl)dimethylamine oxide (MIC = 7.8-78 mumol/L). Iodaminox was about twice as efficient (MIC = 3.9-31 mumol/L). The bactericidal activity of both compounds was tested at different periods of exposure, ambient pH and cultivation temperature on three species of clostridia. The activity of both compounds was the highest at pH 6 and 40 degrees C. PMID- 8365697 TI - Glucomannan from Candida utilis. Structural investigation. AB - Structure of the glucomannan isolated from the cell walls of Candida utilis has been investigated using acetolysis fragmentation, methylation analysis and NMR spectroscopy. The structure of the glucomannan resembles that of the cellular mannans of other Candida species, except that the longer tetra- and pentassacharide side-chains are terminated with a glucosyl residue. Presence of the nonreducing glucosyl groups at the ends of the side-chains caused the C. utilis not to cross-react in a double immunodiffusion test with other Candida species that possess mannan antigens and cross-react with Hansenula species with glucomannan antigens. PMID- 8365698 TI - Turnover of canavanine-containing proteins in Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae grown for 2 h in the presence of 0.5 mmol/L canavanine in a synthetic medium with ethanol as the sole carbon source (OEC) exhibited a slowing down of protein synthesis for 3-4 h after a shift to fresh ethanol-based medium containing 1.0 mmol/L arginine (OEA) in comparison with untreated cells grown on OEA. The change of carbon source from ethanol to glucose (OGA) after growth in the OEC medium resulted in an even deeper decline of protein synthesis. The degradation of canavanine-containing proteins in cells pregrown and labelled in an OEC medium after transfer to OEA was more rapid than in the OGA medium. The initial rate of protein degradation during the first hour in the OGA medium was less than 1%/h whereas in the OEA medium it reached almost 10%/h. The fraction of proteins with high turnover (half-life 0.46 h) constituted 8.3% on OEA, while during subsequent growth on OGA it was only 0.75% with a half-life of 0.12 h. PMID- 8365699 TI - Prenatal expression of the 65-kDa heat-shock protein homologue in pig tissues. AB - A monoclonal antibody (ML30) recognizing the 65-kDa heat-shock protein of mycobacteria and reacting with homologous human protein was found to stain various porcine tissues. Development of this reactivity was studied. The first ML30-positive cells were embryonic hepatocytes. The protein reacting with the ML30 antibody was localized predominantly in the Golgi area and mitochondria of hepatocytes. Cell membranes of some peripheral blood lymphocytes were also found to bind ML30. PMID- 8365700 TI - Modified simplified method for isolation of lysostaphin from the culture filtrate of Staphylococcus staphylolyticus. AB - The present paper reports a modified method for isolation of lysostaphin--a bacteriolytic agent with specific affinity for staphylococcal cell wall. The proposed purification scheme includes three steps. The first procedure is ultrafiltration through a membrane filter giving a yield of 75.6%. The result of ultrafiltration is a concentrated, 10-times purified preparation of lysostaphin with specific activity 0.62 U/mg which can be used for digestion of S. aureus cells. Further step, performed by ion-exchange chromatography on DEAE-cellulose, yields a 60-times purified preparation containing a mixture of enzyme components of lysostaphin. The yield of this step is 47.2%, the preparation contains 3.54 U/mg protein. Using gel filtration on Sephadex G-50 a component with hexosaminidase activity was separated from the endopeptidase component on the basis of molar mass difference. A 270-times purified preparation of lysostaphin endopeptidase with minimum of contaminating substances was obtained in this step. The yield of gel filtration was 22.1%, specific activity increased up to 16.3 U/mg protein. PMID- 8365702 TI - The secondary antibody response induced in tissue cultures. AB - The conditions for induction of memory cells (B-MC) and evocation of the secondary antibody (Ab) response in tissue cultures (TC) were estimated. (1) In vivo primed B-MC cells were isolated 6-150 d after priming and stimulated in TC with different doses of sheep red blood cell (SRBC) antigen. The Ab response has a strict time and dose dependence: only small doses (10(5)) evoke a secondary response, high doses (10(8), 10(9)) a state of immediate tolerance. (2) Antigen added to TC directly with B-MC rescued their Ab production for a long period. Addition of the antigen 1 or 2 d after setting the TC, follows the Ab-response decay, comparable with virgin cells (B-ICC). (3) Primed B-MC stimulated in TC responded preferentially with an IgM secondary response; the same cell suspension adoptively transferred into isologous recipients switched into IgG cells. (4) Virgin, immunocompetent, B-ICC were primarily stimulated in TC with a small dose of antigen (10(5) SRBC); after 7 d of cultivation the cells were transferred into isologous recipients, SCID mice and into TC. In all cases, the secondary response of IgM was determined, 10 times higher than in the primary controls. PMID- 8365701 TI - Comparison of the in vitro effects of several cephalosporins on the oxidative burst of human phagocytes. AB - The metabolic activity (oxygen radical formation) of human phagocytes was not substantially affected by the tested cephalosporins. Therapeutic concentrations caused only a mild suppression or immunopotentiation in some cases or there were no effects altogether. PMID- 8365703 TI - [Neuropathologic, immunologic and psychobiological aspects of Alzheimer's dementia]. AB - This review attempts a consolidated overview of the results of molecular biological research on amyloid pathology in Alzheimer's disease crosslinked with other aspects of the disease that have not been so much in focus in recent years. The spotlight will be on many pointers to an immunological process as part of the Alzheimer pathology. The problem of the specificity of plaques and of neurofibrillary tangles that both are considered to be classical neuropathological markers of Alzheimer's disease is critically reviewed on the basis of existing findings in neuropathology in non-demented and demented elderly persons. The traditional unidirectional concept that interprets the neuropsychological functions inhibited in Alzheimer's dementia merely as sequels to damaged morphological structures, is questioned. Earlier and more recent experimental findings indicating that dysfunctional and deficient use of neuropsychological functions can inhibit neuronal plasticity and can be the origin of morphological changes, are placed in relation to numerous pointers to non-cognitive mental anomalies prior to the outbreak of Alzheimer's disease. In Alzheimer's dementia, pathology of synapses is preferably correlated with neuropsychological deficits. Findings on this pathology are discussed as a possible expression of a neuronal plasticity decrease that is partly conditioned by psychobiological mechanisms. PMID- 8365704 TI - Human ovarian aging and mitochondrial DNA deletion. AB - The functions of human ovary change dynamically around the menopausal period. A decrease of the number of primordial follicles and an increase of fibrous tissues are observed histologically in the aged ovary. As endocrinological aspects at menopause, the synthesis and secretion of ovarian steroid hormones such as estrogens and progesterone decrease, followed with the resultant increases of pituitary gonadotropins. However, the mechanism of menopause and ovarian aging is not well understood. Thus, to study the regulatory mechanism of ovarian dysfunction by aging, we analyzed the accumulation of mitochondrial DNA (mtDNA) mutation in the human ovary in women of various ages. The amplification of a 5.5 kb region in mtDNA with polymerase chain reaction revealed a 0.5-kb band in ovarian samples obtained from menopausal and postmenopausal women, which means that the 5.0-kb deletion of mtDNA in ovarian tissue starts at the menopausal period. The close relationship between the occurrence of ovarian mtDNA deletion and the menstrual irregularity was also observed. These observations suggest that the accumulation of the deleted mtDNA may be a regulating factor of dysfunction of the ovary by aging. PMID- 8365705 TI - Role of the free radical-scavenger system in aromatase activity of the human ovary. AB - The present study was undertaken to clarify the physiological role of the free radical-scavenger system in the control of estrogen production in the human ovary with age. Both superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the homogenate of the ovary significantly decreased from the premenopausal period to the menopausal period. The lipid peroxide content, however, showed a small and gradual decrease from the premenopausal to the postmenopausal period. In the premenopausal women, aromatase (Ar) activity in the microsomal fraction of the ovary showed a sharp decline and a significant negative correlation with age. Significant positive correlations were found between SOD and Ar activity, and between GSH-Px and Ar activity. Treatments of homogenate of the ovary with 10, 50 and 100 microM of H2O2 resulted in a decrease in Ar activity in a dose-dependent manner. Moreover, treatment with 10 and 50 microM of H2O2 produced a more significant decrease in the Ar activity in the premenopausal women than that in the postmenopausal women. Treatments with 0.01, 0.1, 1.0 and 10.0 U of GSH-Px before administration of 50 microM of H2O2, on the other hand, induced a recovery of the Ar activity in a dose-dependent manner. The present study showed the inhibitory effect of peroxide on Ar activity, which was attenuated by GSH-Px. These results seem to suggest that these age-related, relatively free radical predominant environments in the human ovary may have an important role in the decrease of estrogen production through the effects on the Ar activity. PMID- 8365706 TI - Aging changes in the alignment of chromosomes after human chorionic gonadotropin stimulation may be a possible cause of decreased fertility in mice. AB - The relation between the alignment of chromosomes in the aged oocyte and its capacities of fertilization and development of oocytes was examined. More embryos in the condition of insemination at 12 and 16 h after human chorionic gonadotropin (hCG) however grew into two and more cell stages than those in the insemination of 20, 24 and 28 h. Some embryos in the group of insemination at 12, 16 and 20 h after hCG injection had grown into the blastocyst stage. The embryos inseminated 24 h after hCG and later had shown no further development. Twelve hours after hCG injection, 67% of oocytes have chromosomes on a straight line (A), and 29% have chromosomes scattered in one group (B). Three percent of oocytes have them separated toward both spindle ends (C) and 2% of oocytes have no chromosomes (D). At 16 h after hCG, the alignments of chromosomes are almost the same as that of 12 h after hCG injection. At 20 h after hCG, the most common alignment of chromosomes was scattered in a small group. The alignment of chromosomes of most oocytes was splitting at 24 and 28 h after hCG injection. Thus the oocytes with the chromosome alignment of A or B can be fertilized and developed into the blastocyst stage. The alignment of A and B lasts only about 8 h after ovulation, and the time was extremely restricted for oocytes to develop normally. PMID- 8365707 TI - The aging process of the reproductive organs: an overview. PMID- 8365708 TI - Evidence for the involvement of epidermal growth factor in fertility decline in aging female mice. AB - A decline in fertility, defined as the number of implantation sites, was observed in mice as they aged; the decline started at 30 weeks of age and reached a nadir by 60 weeks when no implantation was detected. Epidermal growth factor (EGF) levels in the submandibular gland and plasma increased as the female mice aged, and sialoadenectomy (surgical removal of the submandibular glands) attenuated the rise in the plasma EGF level without affecting the overall health or survival of the animals. Uterine weight at 10-20 weeks of age was about 70 mg, and it significantly increased with age. This weight has increased more than 2-fold by 60 weeks. These changes closely followed the increase in the concentrations of EGF in the submandibular gland and the plasma. After sialoadenectomy, uterine weight decreased immediately and remained at about 50-60 mg throughout the experimental period. Interestingly, sialoadenectomized mice became pregnant at an older age than the controls. These findings suggest that elevated levels of EGF may have a physiological role in fertility decline in aging mice perhaps via uterine hypertrophy. PMID- 8365709 TI - Origin of senescence: a review. AB - The aging process is controlled by dual mechanisms. One is the mechanism which programs ultimate cell death and therefore determines the life-span at birth. The other is the mechanism which causes aging stochastically by damaging certain substances with time in life. Now, these mechanisms have been investigated on genetical bases. Whatever the mechanisms involved in aging, increasing evidence suggests the important roles of oxygen free radicals in the process of aging. PMID- 8365710 TI - Morphological changes in spiral artery of the mammalian ovary with age. AB - Morphological changes which take place in ovarian arteries at different ages in human and monkey, were investigated by light microscopy, transmission electron microscopy and scanning electron microscopy. The ovarian arteries in both species were characterized by a spiral configuration throughout their course. The hilar and medullar arteries were especially convoluted. In the pubertal monkey, the hilar and medullary arteries exhibited some intimal thickenings in which smooth muscle cells of a synthetic phenotype were longitudinally arranged. These arteries in adult monkeys had considerable intimal thickening. In a 30-year-old woman, arteries with intimal thickenings were detected in the hilus and medulla. Around 40 years of age, the intima of the arteries were considerably thickened with a diameter usually equal to half of the wall. In women after menopause, the tunica intima of these arteries was approximately two-thirds or more of the total artery wall thickness. Spiral arteries of the ovary were also thickened with advancing age. PMID- 8365711 TI - Reactive human bile ductules express parathyroid hormone-related peptide. AB - Various cholestatic liver diseases as well as regeneration after submassive necrosis are accompanied by a striking increase in the number of bile ductules. These reactive bile ductules are thought to arise either from proliferation of pre-existing bile ductules or bile ductule-related facultative stem cells, or from ductular metaplasia of hepatocytes. Recently, we found that reactive bile ductules display neuro-endocrine features, and speculated that the substance(s), produced in the neuro-endocrine granules, might play a role in their growth and/or differentiation through an autocrine or paracrine pathway. Parathyroid hormone-related peptide has been shown to be encoded by a growth factor-regulated gene that may play a role in cell growth and differentiation. We studied the immunohistochemical expression of this peptide in human liver, including three normal biopsies, 11 cases of cholestatic liver disease, six cases of focal nodular hyperplasia and three cases of regenerating liver. In regenerating liver, primary biliary cirrhosis, primary sclerosing cholangitis and partial or intermittent obstruction, the majority of reactive ductular cells expressing neuro-endocrine markers also expressed parathyroid hormone-related peptide. In focal nodular hyperplasia, a smaller number of bile ductular cells expressed the peptide. These findings suggest that parathyroid hormone-related peptide is localized in bile ductular cells and may indicate a role for this hormone in the growth and/or differentiation of human reactive bile ductules. PMID- 8365712 TI - Recurrent hepatitis B in liver allografts: a distinctive form of rapidly developing cirrhosis. AB - Recurrent hepatitis B virus (HBV) infection in the liver allograft is a significant cause of morbidity and mortality in those transplanted for chronic HBV disease. A detailed histological and immunohistochemical study of recurrent HBV disease in liver allografts was carried out using archival paraffin-embedded tissue. A total of 34 follow-up liver biopsies from 14 patients transplanted for HBV were available for study. In addition to routine stains, sections were stained with antibodies to a range of HBV antigens. Two patients transplanted for acute HBV remained free of re-infection. Five of seven patients transplanted for chronic HBV disease who were followed-up, developed HBV-associated cirrhosis 12 23 months later. Hepatocyte ballooning, high nucleocapsid antigen load, ductular proliferation and immature fibrous tissue characterized this unusual cirrhosis, which developed rapidly from fibrosing cholestatic hepatitis in at least three cases. Death from liver failure supervened quickly in three of the five patients. These findings support the concept that HBV infection in the liver allograft can be a different disease from that occurring in the non-transplant setting, and may be related to high antigen load. PMID- 8365713 TI - Expression of epidermal and nerve growth factor receptors in human thymus and thymomas. AB - The expression of epidermal growth factor (EGF) and nerve growth factor (NGF) receptors has been investigated by immunohistochemical analysis in eight normal human thymuses and in 15 thymomas. Thymomas were classified into five different histological types--medullary, mixed, predominantly cortical, cortical thymoma and well-differentiated thymic carcinoma. In fetal and paediatric normal thymus, EGF-receptor was expressed by subcapsular, cortical and medullary epithelial cells, whereas immunoreactivity for NGF-receptor was detected on only subcapsular and medullary epithelial cells. In thymomas, independent of their histological type, EGF-receptor was expressed by a large majority of epithelial cells. In contrast, the pattern of expression of NGF-receptor in thymomas was different for the various histological types. These findings indicate that the expression of both EGF and NGF receptors in human thymomas substantially reflects their expression in normal thymus, and suggest that EGF and NGF may play a role in the ontogenesis of the human thymus as well as in the histogenesis of thymomas. PMID- 8365714 TI - Granulomatous gastritis: a morphological and diagnostic approach. AB - The final diagnosis of granulomatous gastritis is based on morphological findings and clinical and laboratory data. Detailed analysis of the morphological features of the granulomas together with associated mucosal changes could generate more information on aetiology and pathogenesis. Biopsies from 71 patients diagnosed as having granulomatous gastritis were reviewed. Thirty-seven of these patients (52%) had Crohn's disease. In 18 patients (25%) an isolated granulomatous gastritis was diagnosed. In seven patients (10%) the final diagnosis was a foreign body reaction. Of the remaining cases, four (7%) corresponded to tumour associated granulomas and one case each of sarcoidosis (1%), Whipple's disease (1%) and vasculitis-associated disease (1%). Two cases (3%) were unclassifiable. The granulomas were mainly found in the antrum (64% antrum only, 11% antrum and corpus, 6% transitional mucosa corpus-antrum). Granulomas were usually small. This was particularly true for those found in patients with Crohn's disease. Multiple granulomas were observed in the sarcoidosis, the Whipple's disease and vasculitis-associated cases. A pattern of chronic gastritis with atrophy was present in 95% of the biopsies (68/71 patients). Helicobacter pylori was detected in 92% of the biopsies (64/71 patients). PMID- 8365715 TI - Prolapse-induced inflammatory polyps of the colorectum and anal transitional zone. AB - A clinicopathological study of polypoid lesions of the lower gastrointestinal tract from 12 patients was undertaken. Clinically, the majority had signs and symptoms of rectal prolapse despite having a variety of other primary diagnoses (e.g. carcinoma of the bowel or diverticular disease). Three patients were asymptomatic. The polyps were more common in females and were usually solitary. Histologically, fibrin 'caps', fibromuscular hypertrophy and obliteration of the lamina propria, goblet cell hypertrophy and serrated tubules were consistently noted. The fibromuscular tissue often extended into the lamina propria in a radial fashion. This study shows that mucosal prolapse underpins a variety of lesions that are part of a histological spectrum of changes. Inflammatory cloacogenic polyps, inflammatory 'cap' polyps, polypoid prolapsing mucosal folds of diverticular disease and inflammatory myoglandular polyps are all due to mucosal prolapse. PMID- 8365716 TI - Primary stromal sarcoma of the thymus with areas of liposarcoma. PMID- 8365717 TI - Uterine tumour resembling ovarian sex cord tumour: evidence for smooth muscle differentiation. PMID- 8365718 TI - Malignant mesenchymoma of the kidney. PMID- 8365719 TI - Intratubular germ cell neoplasia in an infantile testis. PMID- 8365720 TI - The origin of cytologically unidentifiable chromosome abnormalities: six cases ascertained by targeted chromosome-band painting. AB - De novo chromosome structural abnormalities cannot always be diagnosed by the use of standard cytogenetic techniques. We applied a previously developed chromosome band-specific painting method to the diagnosis of such rearrangements. The diagnostic procedures consisted of microdissection of an aberrant chromosomal region of a given patient, polymerase chain reaction (PCR) amplification of the dissected chromosomal DNA, and subsequent competitive fluorescence in situ hybridization (FISH) using the PCR products as a probe pool on metaphase chromosomes from the patient and/or a karyotypically normal person. With this strategy, we studied 6 de novo rearrangements (6p+, 6q+, 9p+, 17p+, +mar, and +mar) in 6 patients. These rearrangements had been seen by conventional banding but their origin could not be identified. In all 6 patients, we successfully ascertained the origin. Using an aberrant region-specific probe pool, FISH signals appeared on both the aberrant region and a region of another specific chromosome pair. A reverse probe pool that was generated through the microdissection of normal chromosomes at a candidate region for the origin of the aberration hybridized with both the aberrant and the candidate regions. We thus diagnosed one patient with 17p+ as having trisomy for 14q32-qter, one with 9p+ as having trisomy for 12pter-p12, one with 6q+ as having a tandem duplication (trisomy) of a 6q23-q25 segment, one with 6p+ as having a tandem duplication (trisomy) of a 6p23-q21.3 segment, one with a supernumerary metacentric marker chromosome as having tetrasomy for 18pter-cen, and the last with an additional small marker chromosome as having trisomy for 18p11.1 (or p11.2)-q11.2. The present targeted chromosome-band-painting method provides the simple and rapid preparation of a probe pool for region-specific FISH, and is useful for the diagnosis of chromosome abnormalities of unknown origin. PMID- 8365722 TI - Physical mapping of chromosome 3p25-p26 by fluorescence in situ hybridisation (FISH). AB - As part of our effort to isolate and characterise the von Hippel-Lindau (VHL) disease gene, we constructed a physical map of chromosome 3p25-26 by fluorescence in situ hybridisation (FISH) studies on a panel of cytogenetic rearrangements involving this region. Biotinylated cosmid and lambda probes were hybridised to metaphase chromosome spreads and positioned with respect to each cytogenetic breakpoint. These studies unequivocally established the order of five loci linked to the VHL disease gene: cen-(RAF1,312)-D3S732-D3S1250-D3S601-D3S18 -pter and determined the position of three other probes within this map. These results ordered RAF1 and D3S732 for the first time, confirmed the localisation of D3S1250 between RAF1 and D3S601 and determined the position of D3S651 with respect to other chromosome 3p25-p26 loci. The establishment of an ordered set of cytogenetic aberrations will enable the rapid assignment of polymorphic and nonpolymorphic cloned sequences within the chromosome region 3p25-p26. PMID- 8365721 TI - Rearrangements between irradiated chromosomes in three-species radiation hybrid cell lines revealed by two-color in situ hybridization. AB - A human-hamster hybrid cell line containing only the human X chromosome (GM06318B) was exposed to 6,000-7,000 rad of X-rays and fused with a mouse cell line (CL1D,TK-). Three radiation hybrids, LXKC40, LXKC50, and LXKC56, were selected among 39 independent clones containing human material. Two-color in situ hybridization with total genomic DNA probes (cot1 human DNA and hamster total genomic DNA) was used to analyse the irradiated chromosome rearrangements. With this three-species model system (human-hamster-mouse) and the chromosome painting process it was possible to determine the origin of each chromosomal fragment in metaphase and interphase. The results obtained indicate preferential rearrangement between irradiated human and hamster chromosomes. Whole, apparently intact hamster chromosomes were observed in all the mitoses. We suggest that these chromosomes could be neoformated from random fragments after irradiation. Hamster and human "minichromosomes" were also detected. While the integration of human material into the mouse genome was exceptional, the integration of hamster material into mouse chromosomes was more frequent. During interphase the irradiated chromosome domains were often at the periphery of the nucleus. Irradiated material protruded at the periphery of the nuclei. Micronuclei containing hamster material were detected in the vicinity of these protrusions. PMID- 8365723 TI - Presence of telomeric and subtelomeric sequences at the fusion points of ring chromosomes indicates that the ring syndrome is caused by ring instability. AB - In situ hybridization of a telomeric (TTA-GGG)n sequence to metaphases from three cases of ring chromosome, involving respectively chromosomes 4, 16, and 20, showed the presence of the cognate sequences in all three rings. To investigate whether these ring chromosomes originated by telomere-telomere fusion, we determined, by in situ hybridization, whether telomere-associated sequences and/or specific distal sequences were still present in the ring chromosomes. The finding that these sequences were preserved in all the ring chromosomes strongly indicates that they originated by telomere-telomere fusion. All three subjects carrying the ring chromosomes are affected by the so-called ring syndrome, with failure to thrive, minor dysmorphic signs and no major anomalies. The r(4) patient has the ring in mosaic form with a normal cell line and has normal intelligence. The r(16) and the r(20) patients have moderate mental retardation and suffer from seizures. We conclude that the ring syndrome, even in its more severe manifestation, is caused by ring chromosome instability. PMID- 8365724 TI - Altered CYP21 genes in HLA-haplotypes associated with congenital adrenal hyperplasia (CAH): a family study. AB - Disorders of the CYP21 gene, which is located within the major histocompatibility complex on the short arm of chromosome 6, are the leading causes of congenital adrenal hyperplasia (CAH). The coding gene and a highly homologous pseudogene are tandemly arranged with the two genes for the fourth component of complement (C4A and C4B). To analyse the prevalence rates of mutations of the CYP21 genes and the segregation of the CYP21 genes with their corresponding human leucocyte antigen (HLA)-haplotypes, 21 families with one or two children with the severe form of 21 hydroxylase deficiency were studied. Mutations of the CYP21 gene on their corresponding HLA-haplotype were detected by hybridisation of polymerase chain reaction (PCR)-amplified genomic DNA with sequence-specific oligonucleotides and solid phase direct sequencing. Our study has shown the following. (1) A single basepair mutation (A-->G or C-->G) within the second intron is the most frequent mutation leading to impaired 21-hydroxylase activity. This mutation is only detected in HLA-haplotypes associated with the salt-wasting form of CAH. (2) A large deletion of part or all of the CYP21 gene is associated with the HLA haplotype A3, BW47, C6, DR7, DR53, DQ2 but is also observed in other HLA haplotypes and can be detected by a simple rapid PCR restriction fragment length polymorphism method. (3) Two alleles of the coding CYP21 gene differing in a leucine codon within the first exon, (formerly described as a mutation associated with 21-hydroxylase deficiency) have been found with an equal distribution in patients with 21-hydroxylase deficiency, non-disease HLA-haplotypes and the local healthy controls. PMID- 8365725 TI - Recurrent mutations in the factor IX gene: founder effect or repeat de novo events. Investigation of the German haemophilia B population and review of de novo mutations. AB - The investigation of 114 unrelated patients, representing about half the sample of the German haemophilia B population, enabled us to delineate the causative mutation in 103 (90.4%) haemophilic factor IX genes. Of these 103 cases 84 (81.6%) turned out to be unique molecular events, the remainder being repeats. Haplotype analysis revealed that the great majority, if not all, of these recurrent observations occurred independently. This conclusion is supported by our finding that three de novo mutations could be demonstrated at two sites of frequent mutation. A further 20 de novo events could be established in an unselected sample of 37 families with sporadic haemophilia B and 37 families with a history of the disease. Altogether, the germ line of origin could be determined in 21 of these 23 cases, thereby indicating a ratio of male to female mutation rates close to 2. On the basis of the data available, it is becoming clear that rearrangements in the factor IX gene (35.4% of de novo cases) are responsible for haemophilia B at a higher frequency than has been observed today (12.3%). More than two-thirds of the de novo cases cause the severe form of the disease, thereby reflecting the deficit of these haemophilic genes in the actual gene pool because of excess mortality in the past. In addition 40% (12/30) of the de novo single-base mutations were transitions at CpG dinucleotides. Compared with the expected at-random frequency, this observation indicates an 83-fold enhancement of mutation at CpG. PMID- 8365726 TI - Four novel gene mutations in five Japanese male patients with neonatal or late onset OTC deficiency: application of PCR-single-strand conformation polymorphisms for all exons and adjacent introns [corrected]. AB - Ornithine transcarbamylase deficiency (OTC), the most common inborn error of the urea cycle, shows an X-linked inheritance with frequent new mutations. Southern blots reveal only a small percent of the mutation, but amplification of cDNA or genomic DNA using the polymerase chain reaction (PCR) followed by DNA sequencing, has contributed greatly to overcoming this difficulty. Problems remaining are the limited availability of fresh liver samples for preparation of intact mRNA in the former case, and there are primer sequences for PCR for only some exons in the latter case. Here, we report the structures of intron sequences which are long enough to analyze all exons and adjacent introns of the OTC gene using PCR and PCR single-strand conformation polymorphisms (PCR-SSCP). We carried out a DNA analysis of findings in five Japanese male patients with neonatal or late onset form. Five patients had mutations in the protein coding region. C to G (S192R), A to T (D196V), A to G (T264A), T to C (M268T), and C to T (R277W) substitutions. The first four of these were novel missense mutations and the presence of the mutation was confirmed in the corresponding families. PMID- 8365727 TI - No relationship between genetic instability in Bloom's syndrome and DNA hypomethylation of some major repetitive sequences. AB - Bloom's syndrome (BS) is an autosomal recessive disorder, characterized by a high incidence of cancer at a young age. Cytogenetically, BS cells exhibit a high frequency of chromosomal damage and sister chromatid exchange (SCE). Thus, BS provides a human model of a genetic disorder exhibiting both chromosomal instability and a high incidence of cancer. In addition to its involvement in gene regulation, CpG methylation has recently been suggested to play an important role in the evolution and stability of chromosome structure. We have examined DNA methylation profiles of total DNA and some selected repeated sequences in normal and BS cells. No specific DNA hypomethylation in either total blood or lymphoblastoid cell lines from BS patients has been detected, suggesting that the genomic instability observed in BS is not directly related to a major DNA demethylation of the total CCGG sites, or of Alu or chromosome 1 satellite 2 repeated sequences. PMID- 8365728 TI - G2 phase cell cycle disturbance as a manifestation of genetic cell damage. AB - The predominant cell cycle change induced by X-rays and clastogens in peripheral blood mononuclear cells is the accumulation of cells in the G2 phase of the cell cycle. We show that this accumulation consists of cells that are either delayed or arrested within the G2 phase. Since both X-rays and DNA crosslinking chemicals are known to damage DNA, the G2 phase inhibition caused by these agents is thought to be one of the primary manifestations of (unrepaired) DNA damage. This interpretation is supported by two additional findings. (1) Older individuals have elevated baseline levels of mononuclear blood cells that are delayed and/or arrested in the G2 phase of the cell cycle. This coincides with the increased chromosomal breakage rates reported for older individuals. (2) Irrespective of their age, individuals with inherited genetic instability syndromes (such as Fanconi anemia and Bloom syndrome) exhibit elevated G2 phase cell fractions. We show that the method used to detect such induced or spontaneous cell cycle changes, viz. BrdU-Hoechst flow cytometry, is a rapid and highly sensitive technique for the assessment of genetic cell damage. PMID- 8365730 TI - Four new nucleotide sequence polymorphisms in the LDL receptor gene detected by SSCP analysis. AB - Seven nucleotide sequence polymorphisms were detected within exons of the low density lipoprotein (LDL) receptor gene using single-strand conformation polymorphism (SSCP) analysis followed by direct sequence analysis on amplified DNA. Four nucleotide changes at nucleotide positions 1617, 1725, 2232, and 2635 were new nucleotide sequence polymorphisms not previously described. The remaining three nucleotide changes were identical with restriction fragment length polymorphisms and a previously reported nucleotide sequence polymorphism. These nucleotide sequence polymorphisms, detectable by SSCP analysis, are useful genetic markers for linkage analysis of the LDL receptor gene and familial hypercholesterolemia. PMID- 8365729 TI - The human complement component C8B gene: structure and phylogenetic relationship. AB - The eighth component of human complement (C8) is a serum protein that consists of three chains (alpha, beta and gamma), encoded by three separate genes, viz., C8A, C8B, and C8G. In serum, the beta-subunit is non-covalently bound to the disulfide linked alpha-gamma subunit. Using a full-length C8 beta cDNA probe, we isolated several clones from human genomic lambda DNA libraries. Four lambda clones covering the complete cDNA sequence were characterized by TaqI restriction mapping and were "shotgun" subcloned into M13. C8 beta-cDNA-positive clones were partially sequenced to characterize the 12 exons of the gene with sizes from 69 to 347 bp. All intron-exon junctions followed the GT-AG rule. By using polymerase chain reaction (PCR) primers located in the adjacent intron sequences, all 12 exons of the C8B gene could be amplified from genomic DNA. All fragments showed the expected sizes. The sizes of eight introns could be determined by using primer pairs that amplified two exons and the enclosed intron, and by restriction mapping. These analyses and the insert sizes of the genomic lambda clones indicate that the C8B gene has a total size of approximately 40 kb. The polymorphic TaqI site of the C8B gene localized in intron 11 could be demonstrated by direct restriction fragment analysis of a PCR fragment containing exons 11 and 12, and the enclosed intron 11. Homology comparison of the C8B gene with C8A and C9 on the basis of the exon structure confirmed the ancestral relationship known from the protein level. PMID- 8365731 TI - Alpha-thalassemia in the four major aboriginal groups in Taiwan. AB - A total of 1309 unrelated blood samples from four major Taiwan aboriginal groups, including 522 of the Ami, 246 of the Bunun, 227 of the Atayal, and 214 of the Paiwan groups, were collected. Subjects with a mean corpuscular volume below 85 fl and Hb A2 values below 3.5% were further studied with Southern hybridization to determine the status of alpha-globin genes. In the Ami, 43 (4.1%) chromosomes had alpha-thalassemia 1 and 43 (4.1%) had alpha-thalassemia 2. Of the 43 alpha thalassemia 1 chromosomes, 33 were of the Thailand, one of the Philippine, and nine of the Southeast Asian deletion. Of the 43 alpha-thalassemia 2 chromosomes, 42 were of the type I rightward deletion and one was of leftward deletion. In the Bunun group, one chromosome (0.2%) was of the Thailand deletion and two (0.4%) were of type I rightward deletion. In the Atayal group, only one chromosome (0.2%) was of the Philippine deletion. In the Paiwan group, four chromosomes (0.9%) were of the Southeast Asian deletion and three (0.7%) were of the Thailand deletion. Among the four groups, the Ami had the highest prevalence of alpha thalassemia, which was also higher than that of the Chinese living in Taiwan. PMID- 8365732 TI - Absence of linkage to the ataxia telangiectasia locus in familial breast cancer. AB - Heterozygotes for ataxia-telangiectasia (AT) are known to have an increased risk of breast cancer. The gene (or genes) responsible for almost all cases of AT has been localised to chromosome 11q by genetic linkage analysis. To examine the possibility that AT heterozygosity may account for a substantial proportion of familial breast cancer, we have typed five markers on chromosome 11q in 16 breast cancer families. We have found no evidence for linkage between breast cancer and chromosome 11q markers and conclude that the contribution of AT to familial breast cancer is likely to be minimal. PMID- 8365733 TI - Newer interventional devices. PMID- 8365734 TI - Transcatheter ablation of ventricular tachycardia arising from right ventricular outflow tract. AB - Two patients with recurrent episodes of symptomatic, sustained monomorphic ventricular tachycardia (VT) resistant to medical therapy underwent catheter ablation for the relief of VT. One patient had arrhythmogenic right ventricular dysplasia while the other had no structural heart disease. The VT had left bundle branch block morphology with normal axis in both the patients. The cycle length during VT was 260 msec and 270 msec respectively. Site for ablation was guided by pacemapping and the target site was identified in the right ventricular outflow tract in both the patients. Two cathodal shocks of 200 J in the first patient and one shock of 200 J in the second patient resulted in abolition of the arrhythmia. At repeat electrophysiologic testing at 7 days in the first patient and at 8 months in the second, VT was not inducible despite three extrastimuli from two right ventricular sites. Over a follow up of 24 and 26 months respectively, there has been no recurrence without any antiarrhythmic therapy. There were no acute or long term complications. In conclusion, catheter ablation offers a cure in patients with right ventricular tachycardia resistant to antiarrhythmic drugs. PMID- 8365735 TI - Antihypertensive therapy and J curve. PMID- 8365736 TI - Sternal wound infection after myocardial revascularization with internal mammary artery. AB - The use of the bilateral mammary artery in myocardial revascularisation in diabetic patients has been thought to increase the risk of sternal wound infection. We studied unilateral IMA grafting retrospectively in 701 consecutive patients to determine the incidence of sternal wound infection. One hundred and six patients were diabetic; 595 were non-diabetic. Both groups of patients were comparable for age, number of bypasses, and cardiopulmonary bypass time. No patient in the diabetic group developed mediastinitis; two patients of 595 in the non-diabetic group (0.3%) developed mediastinitis. Incidence of subcutaneous wound infection was slightly higher in the diabetic group than in the non diabetic group (2% vs 0.3%) but was not statistically significant. We conclude that unilateral internal mammary artery grafting in diabetics is not associated with increased risk of sternal wound infection and should remain the conduit of choice for myocardial revascularization. PMID- 8365737 TI - Percutaneous intraaortic balloon pulsation for management of life threatening emergencies in an intensive coronary care unit. AB - The indications for the outcome of use of intraaortic balloon pulsation (IABP) in 66 patients (65 males, 1 female), in addition to the usual conventional medical therapy, are reported here. IABP was used for treatment of cardiogenic shock (5 patients), acute myocardial infarction with rupture of interventricular septum (2 patients), acute myocardial infarction with refractory left ventricular failure (2 patients), resistant ventricular tachyarrhythmias (5 patients), refractory angina (50 patients) and for hypotension following high risk coronary angiography (2 patients). A Datascope 10.5 F percutaneous balloon was inserted in all, mostly using the left femoral artery. Either definitive treatment (coronary artery bypass surgery or coronary angioplasty) was offered when feasible or the balloon was weaned off. Twelve patients underwent coronary angiography on IABP; while 31 patients had undergone the angiography earlier. Surgery was possible in 33 patients with 90% survival rate. The non surgical group showed 30% survival rate. The complications of IABP encountered were: leg ischaemia (2 patients), septicemia (4 patients) and balloon rupture (2 patients). Our experience suggests that percutaneous IABP is a very useful management procedure for seriously sick high risk patients prior to definitive therapy. Patients who could have a definitive treatment while on IABP, especially the group with refractory angina, did best on a short term follow up. Vascular complications are minimal while on IABP. PMID- 8365738 TI - Does any correlation exist between a high plasma digoxin concentration and an electrocardiogram in younger and older patients. AB - In a group of 152 elderly patients (age range between 65 to 92 years) and 54 patients (aged 35 to 64 years) plasma digoxin level measuring 2.5-6.2 nmol/1 were correlated with the clinical symptoms and the electrocardiogram. The conduction disturbances and arrhythmias as well as the P-R interval, P-T-Q index and corrected Q-T interval in the ECG were analyzed. The clinical symptoms of hypersaturation with digitalis were present in 54.6% of the elderly and 35.2% of the younger patients. Conduction disturbances were found in 42% of the elderly and 22.2% of the younger patients, while arrhythmias appeared in 40.1% of the elderly and 31.5% of the younger ones. 17.8% of the elderly and 46.3% of the younger patients were without these changes. The correlation between P-R interval and high plasma digoxin level in the elderly (p < 0.01) and younger patients (p < 0.05), as well as between the P-T-Q index and high plasma digoxin level in the elderly (p < 0.01) was found. There was no correlation between the corrected Q-T interval and high plasma digoxin level in both groups. No correlation was found between a high plasma digoxin level and serum creatinine level in both groups, neither between a high plasma digoxin level and serum potassium level in both groups. The effect of digitalis has not been shown to be a cause of specific changes in an electrocardiogram neither in the elderly nor in younger patients. However, the association between prolonged P-R interval as well as changes in the P-T-Q index and high plasma digoxin level has been found more often in the elderly than in the younger patients. PMID- 8365739 TI - Mitral valve area by colour flow imaging. AB - Colour Doppler assessment of mitral valve area was carried out in 78 patients with mitral stenosis. The mitral valve area was calculated using the equation pi/4 (a x b), where a = color jet width at the mitral valve in the apical long axis view and b = width of the color jet in a 90 degree rotated view from the apex. The valve area obtained from the color jet was compared with the valve area obtained from the pressure half time. It was found that there was a good correlation between these two measurements (r = 0.82; p < 0.001) while 2D echo derived mitral valve area correlated at an r value of 0.80 (p < 0.001). It is concluded that the new method can be used as an adjunct to currently available methods to assess the severity of mitral stenosis. PMID- 8365740 TI - Intracardiac autonomic ganglion cells in leprosy and dilated cardiomyopathy. AB - Disturbances in cardiac autonomic functions are known to occur in patients of lepromatous leprosy and dilated cardiomyopathy. We have analyzed the number of cardiac autonomic ganglion cells in patients of lepromatous leprosy (2 cases), dilated cardiomyopathy (2 cases) and compared with those of control subjects (2 cases). The average number of ganglion cells in cases of dilated cardiomyopathy (1164) and leprosy (1138) did not show any significant deviation from the average neuronal number of control subjects (1352). PMID- 8365741 TI - Endomyocardial biopsy--its evaluation in cardiac disorders. AB - Endomyocardial biopsies (EMBs) of 47 patients with various cardiac disorders were analysed. Clinically 26 patients were diagnosed as having dilated cardiomyopathy (DCM), 9 myocarditis, six restrictive heart disease and six as Duchenne muscular dystrophy. EMB showed normal histological picture in six cases of DCM and findings consistent with DCM in rest of the twenty cases. None of these biopsies showed evidence of myocarditis. Diagnosis of myocarditis could be confirmed on EMB only in three out of nine clinically diagnosed cases. Cases with restrictive heart disease showed normal biopsy in two, infarction in one, findings consistent with endomyocardial fibrosis in one and amyloidosis in two cases. EMB on six cases of Duchenne muscular dystrophy showed nonspecific histological changes. To conclude, in this series, cases of DCM did not show evidence of underlying myocarditis in endomyocardial biopsies. PMID- 8365743 TI - Mitral and pulmonary balloon valvotomy in pregnant patients. AB - Two pregnant patients, one each with mitral and pulmonary valvar stenosis, underwent successful balloon valvotomy during their third trimester. Single balloon technique was utilised in both and this resulted in a short procedure and fluoroscopy time (9 minutes in patient with mitral stenosis and 3.5 minutes in pulmonary stenosis). The procedure produced satisfactory hemodynamic and symptomatic benefits in both cases with no complications. The patient remained asymptomatic without medications and delivered healthy full term babies at term. Balloon valvotomy is feasible, effective, and safe during pregnancy and should be considered as an alternative to surgery in symptomatic patients refractory to medical therapy. PMID- 8365742 TI - A clinico-hematological study of iron deficiency anemia and its correlation with hyperviscosity symptoms in cyanotic congenital heart disease. AB - The present study was carried out in 33 cases of cyanotic congenital heart disease (CCHD) to determine the prevalence of iron deficiency anemia (IDA) and its correlation to hyperviscosity symptoms in terms of hematocrit levels. Furthermore, the study was aimed at assessing the response to low dose iron therapy (60 mg of elemental iron once daily) in relieving symptoms of hyperviscosity. All these cases were evaluated for presence of symptoms of hyperviscosity and later subjected to various hematological & biochemical parameters of iron deficiency anemia including hemoglobin (Hb), pack cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), serum iron, total iron binding capacity respectively. Results showed presence of IDA in 6/33 cases (18.2%) and hyperviscosity symptoms in 10/33 cases (30.3%). Amongst the group with symptoms of hyperviscosity, in the subset having IDA these symptoms were observed at PCV levels of 0.52 L/L to 0.58 L/L in contrast to the subset not deficient in iron where the symptoms occurred at a PCV 0.68 L/L. Relief of symptoms of hyperviscosity was evident with a minimal rise of mean hemoglobin by 2.1 gm/dl. It was concluded that IDA was not an uncommon finding in CCHD cases and that it leads to symptoms of hyperviscosity at a level of PCV much lower than those known to produce these symptoms. Finally low dose iron therapy was found effective in relieving the symptoms of hyperviscosity. PMID- 8365744 TI - Two-dimensional echocardiographic diagnosis of subaortic aneurysm. AB - Subaortic aneurysms are uncommon and most cases have been reported among black Africans. The present report relates to our experience with three patients having subaortic annular aneurysms, two of congenital origin and one following infective endocarditis of the aortic valve. The role of transthoracic 2- dimensional echocardiography in the diagnosis is emphasized. PMID- 8365745 TI - Multiple hydatid cysts involving the heart, pulmonary trunk and aorta. PMID- 8365746 TI - Primary leiomyosarcoma of the left atrium. PMID- 8365747 TI - Intravenous thrombolytic therapy in unstable angina. AB - One hundred consecutive age and sex-matched patients of 3 different subsets of unstable angina (recent onset angina -65, crescendo angina -20, post-infarct angina-15) were randomized 1:1 after coronary angiography to receive I.V., either 1.5 x 10(6) units of streptokinase (SK) in 200 ml of normal saline or 200 ml of normal saline alone (control) in 1 hour. Repeat angiography was done in those patients having intra-coronary thrombi (37.3%) during the initial angiography. Both groups received optimal doses of heparin followed by warfarin, aspirin and other standard drugs and were followed up for 6 months. Anginal pain subsided significantly in the SK group-41 (82%) vs 25 (50%) (P < 0.005), especially in patients with recent onset angina (92.5% vs 60%, P < 0.005). Incidence of acute myocardial infarction (AMI) was much less in the SKgp (4(8%) vs 17 (34%) (p < 0.05). Four cases of fatal MI and four cases of sudden cardiac death (SCD) occurred in the control group against none in the SKgp. Requirements of mechanical revascularization was significantly less (P < 0.05) in the SK gp. Angiographic evidence of partial or complete clot lysis was noted in 90% of SK gp. vs 4.8% of control (P < 0.01). Echocardiographically assessed LV function improved significantly with SK-therapy in recent onset (P < 0.05) and crescendo angina (P < 0.001) subsets--however, the improvements in post infarct angina subset were not statistically significant. The beneficial outcome with SK therapy was observed in patients irrespective of angiographic evidence of thrombi.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365748 TI - Balloon dilatation of native coarctation of aorta in infancy: immediate and follow up results. AB - We attempted balloon dilatation of native coarctation of aorta in 11 consecutive neonates and infants (age range 28 days-12 months, mean 4.6 +/- 4 months, all males) presenting with congestive heart failure. The peak to peak aorto-aortic systolic pressure gradient fell from 60 +/- 21 mmHg to 13 +/- 7 mmHg (range 0-30 mmHg) (p < 0.001). The diameter of coarcted segment increased from 2.5 +/- 0.65 mm (range 2-3.4 mm) to 5.4 +/- 0.9 mm (range 4-6.4 mm) (p < 0.001). No patient required surgical intervention. The peak instantaneous aorto-aortic systolic Doppler pressure gradient at 17.5 +/- 8.8 months (range 2-21 months) did not show any significant change (mean 17.5 +/- 8.89 mmHg range 0-30 mmHg). All patients except one showed improvement in congestive heart failure. None developed restenosis. On the basis of this experience we recommend that balloon dilatation of native coarctation of aorta in infants in congestive heart failure is a safe and effective procedure. PMID- 8365749 TI - Aortic valve replacement with concomitant open mitral valvotomy--early results and long term followup in 72 consecutive patients. AB - Experience with 72 consecutive subjects, who underwent aortic valve replacement with open mitral valvotomy is presented. Mean age was 30 years and history of rheumatic fever was forthcoming in 80%. 91.7% patients had aortic regurgitation- with or without aortic stenosis. 45% patients had pulmonary hypertension. Starr Edwards (51.4% and Bjork Shiley valves (45.8%) were commonly used. There were no early deaths. All patients were followed up for 1 to 19 years (mean = 9 years). There were 4 (5.5%) late deaths. 4.1% patients developed mild restenosis of the mitral valve over a mean period of 8 years and 1.04% developed mitral regurgitation mandating mitral valve replacement. A notable feature of this series is the low incidence of thromboembolism-free lives at upto 10 years followup despite receiving only aspirin in place of coumarin anticoagulation. We believe aortic valve replacement and open mitral valvotomy is a worthy alternative to double valve replacement in view of its zero hospital mortality, low late mortality, low incidence of restenosis, low thromboembolic episodes and the avoidance of coumarin anticoagulation. PMID- 8365750 TI - Limitations of using arterial conduit for myocardial revascularization in patients with combined coronary and other arterial lesions. AB - To explore the limitations of using arterial conduit for myocardial revascularization in patients with combined coronary and other arterial lesions, we evaluated 195 patients with combined lesions undergoing CABG, either alone or in combination with peripheral vascular reconstruction between October 1987 to October 1990. Doppler flow and spectral analysis revealed that 14 patients (7.1%) had atherosclerotic lesions of the subclavian artery, in whom ipsilateral internal mammary artery pedicle graft was contraindicated for myocardial revascularization. Out of 195 patients, 165 patients were subjected for aortography, 18 of whom (10.9%), revealed atherosclerotic involvement of the celiac trunk, thereby contraindicating the use of gastroepiploic artery for myocardial revascularization. Thus in our experience use of arterial conduit for myocardial revascularization in patients with combined coronary and other arterial lesions is limited. PMID- 8365751 TI - Pattern of hypertrophy of left ventricle--a histometric analysis of eighteen cases. AB - The pattern of myocardial hypertrophy in different sites of the left ventricular wall was morphometrically analysed in aortic stenosis (6 cases), hypertensive hypertrophy (5 cases), mitral incompetence (4 cases), and dilated cardiomyopathy (3 cases). The diameter of individual circumferentially oriented mid wall (or middle) fibre was significantly greater than those of subepicardial and subendocardial zones. Thus, hypertrophy does not affect the entire left ventricular myocardium uniformly. It seems to vary according to the spatial configuration of the fibrosis in relation to the cavity. PMID- 8365752 TI - Influence of cessation of smoking on long term mortality in patients with coronary heart disease. AB - Cessation of smoking in patients with coronary artery disease (CAD) has shown variable results. The long term mortality in patients of coronary heart disease (CHD) who quit smoking following diagnosis of their disease has been variable. We have analysed the long term effects of cessation of smoking on mortality in a cohort of 173 patients with CAD and compared the mortality of this group with 299 nonsmokers and 52 current smokers. The baseline data were identical for major risk factors like age, hypertension, diabetes, cholesterol levels, and congestive heart failure among the three groups (p > 0.1). There were more patients with previous myocardial infarction in past (38.7%) and current smokers (40.4%) than among nonsmokers (25.4%). All patients were followed for a period extending upto 11 years. The mean duration of follow up was 6.81 +/- 2.95 years in non-smokers, 5.98 +/- 2.94 years in exsmokers, and 6.32 +/- 3.44 years in current smokers. Actuarial analysis shows that overall mortality was significantly more among exsmokers than nonsmokers (Logrank test = 3.72, 1p < 0.05). The exsmokers showed similar mortality as current smokers during the first three years of follow up (Logrank test = 1.10, 1p < 0.1); but afterwards the mortality was significantly less in exsmokers than in current smokers (Logrank test = 6.29, 1p < 0.025). However, the overall mortality was lowest in nonsmokers when compared to that of exsmokers and current smokers (Logrank test = 3.92, p < 0.05). The total mortality was 28.1% in nonsmokers, 32.4% in exsmokers, and 46.2% in current smokers. The incidence of sudden death was, however, similar in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365753 TI - Non-bacterial thrombotic vegetation mimicking a left ventricular outflow tumor. PMID- 8365754 TI - Ectopia cordis: report of two cases. PMID- 8365755 TI - Functional and histological abnormalities of the left ventricle in Ebstein's anomaly of the tricuspid valve. PMID- 8365756 TI - A case report of primary chylopericardium. PMID- 8365757 TI - Aspirin in ischemic heart disease--an overview. AB - Aspirin is one of the oldest and most commonly used nonprescription drugs in the world. Although commonly it is used for relief from common headache and muscular pain, its use in the prevention and treatment of platelet related complications in cardiovascular diseases (CVD) and cerebrovascular disease (CBVD) is quite controversial. A brief review of the major aspirin trials indicated that a full strength aspirin taken daily had no significant beneficial effect in reducing mortality of patients with CVD/CBVD. However, two major trials (ISIS-2, PHS) in which either low dose aspirin (160 mg) or one aspirin administered every other day, have demonstrated significant reduction in fatal and nonfatal cardiovascular events. Even a dose as low as 1 mg aspirin per day significantly lowers platelet thromboxane synthesis. As a result of these studies, low dose aspirin should be the choice of prophylactic therapy aimed at the inhibition of platelet cyclooxygenase activity. Controlled-release low dose aspirin may favorably reduce platelet thromboxane production and spare vascular prostacyclin synthesis. At least 100 mgs of aspirin per day are essential to completely inhibit steady state thromboxane formation. Low dose aspirin (160 mgs) has been shown to be as effective as the full strength aspirin (325 mgs) in reducing clinical complications related to platelet activation. The antithrombotic effect of aspirin is well established and improved formulations, well thought out therapeutic protocols, customized dosage, appropriate timing of delivery, a better understanding of platelet function and pathophysiology of CUD/CBUD will facilitate maximization of the beneficial effects of aspirin. PMID- 8365758 TI - Color Doppler echocardiographic assessment of Sorin mitral prosthetic valve. AB - Doppler echocardiographic characteristics of 57 normally functioning Sorin prosthetic valves (a tilting valve) in the mitral position were studied in the early postoperative period. The three valve sizes (in mm) studied were: 25 (n = 15), 27 (n = 32) and 29 (n = 10). The mean gradients (mmHg) and the valve area (Sq cm) calculated by pressure half time method) for the three valve sizes were 3.46 +/- 1.69 and 2.49 +/- 0.26; 3.46 +/- 1.25 and 2.57 +/- 0.44; and 3.2 +/- 1.23 and 2.55 +/- 0.41; respectively. There was no significant difference in gradients and valve area between the three sizes, variations in pressure half time and therefore the calculated valve area was large. Color Doppler evaluation revealed a bifid nonturbulent jet directed anteriorly towards the interventricular septum. 12 patients (20%) had mild valvar and 7 (12%) had paravalvar mitral regurgitation (mild in 5 and moderate in 2) without any associated prosthetic valve dysfunction. The paravalvar regurgitation persisted in all the 5 patients restudied at 5-12 months postoperatively. Sorin prosthetic valves have similar gradients and valve area when compared to other disc valves. The incidence of of paravalvar regurgitation was slightly higher in our series. The limitations of Doppler derived gradients and area of prosthetic valve are discussed. PMID- 8365759 TI - Evaluation of prosthetic valve function: utility and limitations of echo-Doppler studies. PMID- 8365760 TI - Role of two-dimensional echocardiography in early diagnosis of suspected acute dissection of ascending aorta. AB - Seven patients with acute dissection of ascending aorta are presented and the role of two-dimensional echocardiography in the early diagnosis of this condition is emphasized. There were 5 male and 2 female patients. The mean age of the patients was 36.7 +/- 11.2 years. The presenting symptoms were chest pain in 7, associated interscapular pain in 4, dyspnoea in 4 and syncopal episodes in 2 patients. Examination revealed hypertension in 3, pulses paradoxus in 2, asymetrically weak carotid and brachial pulses in 3, aortic regurgitation in 5 and neurological deficit in 2 patients. Echocardiography showed aortic root diameter of 42mm and the presence of an intimal flap in all the 7 patients and flap oscillations in 6 patients. Echocardiographic evidence of pericardial effusion was present in 6, cardiac tamponade in 3, aortic regurgitation in 5 and regional left ventricular wall motion abnormality in 1 patient. Surgical correction was done in 5 patients with 60% success rate. Two patients received only medical treatment. Aortic root dilatation of 60 mm, presence of an oscillating flap, evidence of cardiac tamponade and regional wall motion abnormality were found to be associated with poor prognosis. PMID- 8365761 TI - Studies of cancer in migrant populations. PMID- 8365762 TI - Cancer in Italian migrant populations. Sao Paulo, Brazil. PMID- 8365763 TI - Italian migration: an overview. PMID- 8365764 TI - Cancer in Italian migrant populations. Uruguay. PMID- 8365765 TI - Cancer in Italian migrant populations. Australia: mortality study. PMID- 8365766 TI - Cancer in Italian migrant populations. New South Wales, Australia. PMID- 8365767 TI - Cancer in Italian migrant populations. France. PMID- 8365768 TI - Cancer in Italian migrant populations. Geneva, Switzerland. PMID- 8365769 TI - Cancer in Italian migrant populations. England and Wales: mortality. PMID- 8365770 TI - Cancer in Italian migrant populations. England and Wales: incidence. PMID- 8365771 TI - Cancer in Italian migrant populations. Scotland. PMID- 8365772 TI - Cancer in Italian migrant populations. Summary of the results by site. PMID- 8365773 TI - Cancer in Italy: incidence and mortality. PMID- 8365774 TI - Review of studies of cancer in Italian migrants. PMID- 8365775 TI - Cancer in Italian migrant populations. Study objectives and protocol. PMID- 8365776 TI - Cancer in Italian migrant populations. Statistical methods. PMID- 8365777 TI - Cancer in Italian migrant populations. Distribution of risk factors in Italy and in the host countries. PMID- 8365778 TI - Cancer in Italian migrant populations. Canada. PMID- 8365779 TI - Cancer in Italian migrant populations. The United States of America. PMID- 8365780 TI - Cancer in Italian migrant populations. Argentina. PMID- 8365781 TI - Nephrotic syndrome: present status. II. PMID- 8365782 TI - Ultrasound evaluation of kidney dimensions in neonates. AB - This study was done to measure normal renal dimensions of neonatal kidney at various gestational ages sonographically. Knowledge of these measurements may allow earlier diagnosis of a variety of abnormalities. Kidney dimensions (maximum longitudinal length, width, and anteroposterior diameter) were measured within 48 h after birth in 100 healthy neonates with gestational ages from 26.14 to 41.28 weeks and birth weights from 540 to 3250 g using a real time sector scanner with a 7.5 mHz transducer. Renal volume was calculated by volume (V) = L x W x T x 0.5233. Total body surface area (BSA) was determined by BSA = Wt0.425 x Lt0.725 x 71.84. Ponderal index was determined by PI = Wt (g) x 100/(Ht[cm])3. On linear regression analysis, a highly significant correlation was found between renal dimensions and body surface area, gestational age, body weight and length of the baby (p < 0.05). On step wise regression analysis, renal dimensions correlated only with body surface area and the gestational age of the neonate. Regression equations have been provided for rapid computation of renal length, width, and thickness in a given case based on body surface area and the gestational age. Mean (+/- 2 SD) renal volume and renal length were determined based separately on gestational age and body surface area. The data provided can be valuable for evaluating renal abnormalities in preterm neonates. PMID- 8365783 TI - Intramuscular injection as a provoking factor for paralysis in acute poliomyelitis. A case control study. AB - In order to identify the role of intramuscular injection (IM) as a provoking factor for poliomyelitis, a case control study as done at the Institute of Child Health, Madras from May 1988 to May 1989. The case was defined as acute poliomyelitis if he had acute asymmetric flaccid paralysis of lower motor neurone type without objective sensory disturbance following a short episode of fever. Controls were taken from children attending outpatient department for fever. Two controls matched for aged and sex were recruited for each case. Recruitment, data collection and clinical examination were done by a single pediatrician. IM injection received within 30 days prior to onset of paralysis or illness was considered to be the risk factor. The total number of cases and controls recruited were 257 and 515, respectively. Among cases, 172 (66.9%) out of 257 and among controls 252 (48.9%) out of 515, received IM injection within one month earlier to onset of paralysis or illness. The overall risk of paralysis, estimated for IM injection, was increased [odds ratio (OR) 2.1 (95% CI, 1.5 3.0)]. The maximum risk for paralysis was observed to be 2 weeks preceding the illness; the ORs for < 7 days was 2.2 (95% CI, 1.6-3.2) and for 7-13 days 3.2 (95% CI, 1.8 to 5.8). The risk of paralysis associated with IM injection was similar for unimmunized and immunized cases (OR 2.4 and 2.2). Multiple injections were not associated with a higher risk of developing paralysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365784 TI - Dermatoglyphics in cleft lip and cleft palate anomalies. AB - Dermatoglyphic characteristics of sixty nine cases of cleft lip with or without cleft palate and twenty eight isolated cleft palate cases were evaluated for digital patterns, interdigital patterns, palmar simian crease and sydney line, and model types of C- and D-line terminations. Increased frequency of ulnar and radial loops than the arches and whorls was observed in cleft lip with or without cleft palate patients compared to controls. Interdigital patterns were less frequent in cleft lip and cleft palate patients. Simian crease and Sydney line were more common in patients than in controls. Model types of C- and D-line terminations showed variations in patients and controls. Wider 'atd' angle (more than 30 degrees) and dermatoglyphic asymmetry were noted in the patient groups. The findings suggest the dichotomy or heterogeneity of cleft lip and cleft palate anomalies. The role and utility of dermatoglyphics in genetical etiology of congenital defects were emphasized. PMID- 8365785 TI - Diagnostic and prognostic role of CRP and m-ESR in neonatal septicemia. AB - Serial estimation of CRP and m-ESR was done in 65 clinically suspected cases of septicemia and 25 healthy controls. Of these 65, 12 (18%) had a negative CRP test at the time of diagnosis and rest all had significantly elevated CRP and m-ESR compared to matched controls at the time of diagnosis. A persistently negative CRP test indicated bad prognosis. With treatment a declining trend of CRP was seen in survivors, but in deteriorating/expired babies the levels kept on increasing. However, m-ESR had no prognostic significance. PMID- 8365787 TI - Mixed bacterial meningitis. PMID- 8365786 TI - Utilization of maternal services in west Bengal. AB - A study was conducted in selected blocks of West Bengal to assess the utilization of available maternal health services specially immunization, antenatal care and other services. Coverage with two doses of tetanus toxoid levels varied between 58.6 to 86.7% but it fell far short of Universal Immunization Programme target of 100%. Drop out rates were slightly higher in the rural areas. It was observed that in 5 out of 7 blocks more than 55% of the deliveries were conducted either at hospital or Primary Health Centre by health personnel. However, untrained dais predominated over the trained dais in conducting deliveries in most of the areas. This indicates the poor availability or utilization of the latter. PMID- 8365789 TI - Neonatal herpes. PMID- 8365788 TI - Pendred's syndrome. PMID- 8365790 TI - Breast feeding in difficult situations. PMID- 8365791 TI - Postoperative hyponatremic convulsions in two malnourished children. PMID- 8365792 TI - Plasmodium vivax malaria presenting as hemolytic--uremic syndrome. PMID- 8365793 TI - Serum magnesium, calcium, zinc in infantile tremor syndrome. PMID- 8365794 TI - Diazepam intoxication in neonates. PMID- 8365795 TI - Oral steroids in the treatment of periorbital hemangioma. PMID- 8365796 TI - Radial immunodiffusion versus serum protein electrophoresis as a tool for diagnosis of alpha-1-antitrypsin deficiency. PMID- 8365797 TI - Role of prostaglandins in congenital heart disease. PMID- 8365798 TI - Congenital multifocal osteomyelitis. PMID- 8365800 TI - Intradiploic hemangioma of skull bone. PMID- 8365799 TI - Fetus in fetu. PMID- 8365801 TI - Attitudes of medical students towards IAP Pediatric Quiz. AB - Attitudes of medical students towards IAP Pediatrics Quiz were assessed, using a 5 point pre-tested, standardized Likert type scale, developed in our own department. Students had a favorable attitude towards the Quiz and felt that it helps them in the study of Pediatrics, but they are not able to devote sufficient time for preparations because of their preoccupation with other major subjects. The attitudes demonstrated a decline towards unfavorableness when comparison was made between the scores of third year and final year medical students. The difference was statistically significant (p < 0.05). It is suggested that the timing of the Quiz should be changed, so that it doesn't coincide with final professional examinations. This will make it more popular besides generating interest of medical students in Pediatric. Giving more weightage to Pediatrics in university examinations is also re-emphasized as a means of making students more interested in pediatrics. PMID- 8365802 TI - Report of the sub-committee for curriculum in pediatrics for undergraduate medical education. PMID- 8365803 TI - Acute reversible cerebellar ataxia in typhoid fever. PMID- 8365804 TI - Chorea--a rare complication of enteric fever. PMID- 8365806 TI - Polioparalysis in immunized and unimmunized children. PMID- 8365805 TI - Treatment of inverted nipples using disposable syringe. PMID- 8365807 TI - Gene therapy: principles and potentials. PMID- 8365808 TI - Drug use in infection control--is more less? PMID- 8365809 TI - Topical antimicrobial prophylaxis of nosocomial pneumonia in mechanically ventilated patients. Microbiological observations. AB - Generally, reduction of colonization and infection with potentially pathogenic microorganisms in intensive care units (ICU) is attempted by a combination of antimicrobial agents administered topically in the digestive tract and systematically. We tested the efficacy of topical antimicrobial prophylaxis of the oropharynx and stomach administered in combination with sucralfate without systemic prophylaxis in 25 mechanically ventilated ICU patients. The regimen successfully reduced colonization with potentially pathogenic microorganisms in the oropharynx and trachea without modifying the intestinal flora. However, colonization and infections with gram-positive cocci and gram-negative rods other than Enterobacteriaceae and Pseudomonadaceae and resistant to one or both the antimicrobial agents used were observed. PMID- 8365811 TI - Aerosolized pentamidine versus i.v. pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia. AB - The efficacy and toxicity of aerosolized pentamidine was evaluated in 78 AIDS patients given 60 mg biweekly as secondary prophylaxis against Pneumocystis carinii pneumonia (PCP). Patients were monitored for clinical progression and mortality and were compared to 42 historical controls given 200-300 mg i.v. pentamidine biweekly. The relapse rates did not differ markedly between the two groups, and the PCP-free rates in survivors were at 12 months 0.83 and 0.77, respectively. Seventy-one new AIDS-defining events and 25 deaths were recorded in patients on aerosolized pentamidine compared to 29 AIDS events and two deaths in patients on intravenous pentamidine. Recurrent PCP contributed to death in only one case of the aerosolized pentamidine group. PCP is not a serious clinical problem in immunodeficient patients taking pentamidine prophylaxis by either route compared to the progression of clinical HIV disease and death. PMID- 8365810 TI - Differences in verotoxin neutralizing activity of therapeutic immunoglobulins and sera from healthy controls. AB - Intestinal infection by Escherichia coli O157 and other verotoxin (VT) producing E. coli has been increasingly recognized as an important factor for the causation of classic (enteropathic) hemolytic uremic syndrome (HUS) and hemorrhagic colitis (HC). Toxins most frequently involved are VT1 and VT2. As with other toxin mediated diseases, administration of immunoglobulin (Ig) may be beneficial. However, little is known about the immune response elicited by the toxin(s), and the prevalence of VT neutralizing antibodies in the healthy population. We studied the capacity of seven Igs and a commercial plasma preparation to neutralize four different VTs (VT1, VT2, VT2c and VT2e). The results were compared with the neutralization titers (NT50%) of normal human serum samples from various age groups. Plasma products and normal sera were separated by protein G affinity chromatography to investigate the factor(s) responsible for VT neutralization. All Igs neutralized VT1 (8 to 96 NT50%). None of them inhibited VT2, VT2c or VT2e effectively. In contrast, none of 40 pediatric, and only one of 20 adult control sera (starting dilution 1:4) neutralized VT1 (25 NT50%). All 60 samples as well as the plasma preparation blocked VT2 (22 to 446 NT50%, median 137), but not VT2c and VT2e. The VT1 neutralizing activity was eluted with the IgG fraction. The VT2 neutralizing activity was not bound by protein G, but was recovered in the IgG-free effluent. In conclusion, therapeutic Igs significantly neutralize VT1, but are largely ineffective against other VTs. In contrast, all control sera inhibited VT2, but rarely VT1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365812 TI - Detection of Toxoplasma gondii in AIDS patients by the polymerase chain reaction. AB - In recent years, toxoplasmosis has become one of the most frequent and life threatening opportunistic infections in AIDS patients. Despite strict clinical follow-up and repeated biological examinations, its diagnosis remains difficult to establish in the context of immunodeficiency because of the poor predictive value of serology. The aim of the study was to compare standard methods of diagnosis with the polymerase chain reaction (PCR), in an attempt to investigate the potential usefulness of PCR in the diagnosis of toxoplasmosis. Twelve biological samples (cerebrospinal fluid, bronchoalveolar lavage fluid, one brain biopsy and one liver biopsy) from 11 unselected AIDS patients were tested by PCR. The results showed good correlation (for eight out of 11 patients) between classical methods and PCR, and confirm the value of bronchoalveolar lavage for the diagnosis of toxoplasmosis in AIDS patients. The pathophysiological significance of the presence of Toxoplasma in samples tested is discussed. PMID- 8365813 TI - Immunity to measles in young adults in Israel. AB - The likelihood of an epidemic of measles in 1990-92 in Israel prompted us to study the immune status against measles in a random sample of 454 recruits aged 18-19 years in order to obtain data that might be used in determining vaccination policy. This cohort had received one dose of measles vaccine at 12 months of age. The measles immunity status was studied by determination of antibody values that were measured by means of an enzyme-linked immunosorbent (ELISA) IgG antibody test. Of the recruits, 84.6% were found to have positive sera for anti-measles IgG antibodies, while 13.7% had negative sera. Eight (1.7%) subjects had borderline results. The results of this study indicate the need to administer a second dose of measles vaccine at an older age in addition to the MMR (measles, mumps, rubella) vaccine that is now given in Israel at 12 months of age. This step will help achieve the World Health Organization's target of complete eradication of measles. PMID- 8365814 TI - Disseminated intravascular coagulation associated with disseminated cryptococcosis in a patient with acquired immunodeficiency syndrome. AB - Disseminated intravascular coagulation (DIC) is uncommon in acquired immunodeficiency syndrome (AIDS), despite the high incidence of infectious diseases. We describe an HIV-infected patient presenting with disseminated cryptococcosis, who had clear-cut laboratory evidence of progressively worsening DIC (thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, hypofibrinogenemia, increased fibrin(ogen) degradation products and D Dimer, reduced antithrombin III), although the clinical signs of the disease were rather scarce. The patient died despite intense treatment, which included heparin and fresh frozen plasma, and DIC was confirmed histologically. It is suggested that, in a patient with AIDS presenting with an opportunistic infection, laboratory signs of DIC should be carefully checked to early recognize this complication and promptly initiate the required therapy. PMID- 8365816 TI - Brevibacterium species as a cause of osteomyelitis in a neonate. AB - A case of osteomyelitis of the sternum due to Brevibacterium sp. in a neonate following mastitis of the mammary gland 20 days previously is described. The disease was successfully treated with cefazolin and oxacillin. The results of microbiological examinations and their significance are discussed. PMID- 8365815 TI - Multiple brain abscesses and bacteremia in a child due to Fusobacterium necrophorum. AB - A case of Fusobacterium necrophorum bacteremia and multiple brain abscesses in a 6-year-old child following a Mycoplasma pneumoniae infection is described. Brain abscess due to this microorganism has only been described in three other cases since 1977. The clinical picture was consistent with postanginal septicemia, with septic metastatic complications normally only seen in teenagers and young adults. The patient was successfully treated with a 2-month course of parenteral penicillin G and metronidazole. PMID- 8365817 TI - Cross-reactivity of monoclonal antibodies and sera directed against lipid A and lipopolysaccharides. AB - The cross-reactive capacity of monoclonal and polyclonal lipid A antibodies was tested with rough and smooth lipopolysaccharides (LPS). The antibodies represented different specificities recognizing epitopes in the hydrophilic lipid A backbone. In none of the various assay systems applied did the antibodies react with complete rough or smooth-form LPS. Cross-reactions, in general, were only detected with the most rudimentary rough LPS tested, i.e. Re-LPS. A variety of reactivities with other LPS was shown not to be related to lipid A antibodies; such reactivities were present in rabbit sera as well as in crude ascites. These results underline the need for careful checks on the origin of reactivities observed. In addition, rabbit antisera raised with R- and S-LPS were screened for lipid A reactivity using synthetic lipid A and partial structures as antigens. No cross-reactivity of LPS antibodies with lipid A was detected in these sera. PMID- 8365818 TI - Ampicillin and ampicillin-sulbactam dilution tests with mixed cultures of Bacteroides fragilis, Escherichia coli and Enterococcus. AB - Bacterial interactions in mixed infections may compromise antimicrobial therapy. The in vitro bactericidal activity of ampicillin and ampicillin-sulbactam against aerobic/anaerobic mixed cultures of Bacteroides fragilis, Escherichia coli and Enterococcus spp. was studied by means of broth dilution tests. The MBC of ampicillin for Enterococcus faecalis 6 was 0.25 mg/l when tested singly; in association with B. fragilis 1, however, the MBC for E. faecalis 6 was 16 mg/l. When tested singly E. coli 9 and B. fragilis 1 were both killed by ampicillin at a concentration of 4 mg/l in combination with 1 mg/l sulbactam. When both strains were associated, the MBC for B. fragilis 1 rose to > 256 mg/l. Results obtained indicate that the behaviour of bacteria as determined in pure cultures is not necessarily identical with the antibiotic susceptibility present in mixed cultures. It was shown that, besides beta-lactamase production by involved bacteria, other factors contribute to the alteration of bacterial susceptibility in mixed cultures. Synergistic and antagonistic effects between associated organisms were observed. For example, it was found that two moderately sensitive bacterial strains were resistant in mixed culture. PMID- 8365819 TI - Haemophilus influenzae septic arthritis in a healthy adult. PMID- 8365820 TI - Cryptococcal pleural effusion as first indicator of AIDS: a case report. PMID- 8365821 TI - Significant decrease of titres of circulating IgG after oral intake of a preparation of Enterococcus faecalis in a group of ten healthy volunteers. PMID- 8365822 TI - Melatonin increases antigen presentation and amplifies specific and non specific signals for T-cell proliferation. AB - Our preceding results have shown that melatonin administration to normal and immunodepressed mice increases significantly the antibody response. We also found that melatonin is able to restore the impaired T-helper cell activity in immunodepressed mice. The present study shows that melatonin enhances antigen presentation by splenic macrophages to T-cells. This effect is concomitant with an increase in the expression of MHC class II molecules and production of IL-1 and TNF-alpha. Considering the role of antigen presentation and cytokine production in the initiation of the immune response, the present findings provide evidence for relevant mechanisms that may account for the regulatory role of the pineal gland in immunoregulation. PMID- 8365823 TI - Enhanced expression of interleukin 6 in rat and murine arthritis models. AB - Interleukin 6 (IL-6) is a multifunctional cytokine and plays an important role in host defense mechanisms. Enhanced production of IL-6 has been reported in polyclonal B-cell abnormalities and autoimmune diseases such as rheumatoid arthritis (RA). To investigate the role of IL-6 inflammatory joint diseases, serum IL-6 levels of three animal models of RA, namely type II collagen (CII) induced murine, rat arthritis and adjuvant-induced rat arthritis, were monitored. In these models, serum IL-6 increased with the development of arthritis. Serum IL 6 was not elevated by immunization with a non-arthritogenic immunogen such as bovine type I collagen (CI) and bovine serum albumin (BSA) to DBA/1J mice. The serum IL-6 level was correlated well with the severity of adjuvant-induced arthritis. The elevated IL-6 in sera may be associated with the overproduction of IL-6 at the arthritis paws, because higher IL-6 activity was detected in the homogenates of arthritic paws as compared with the control paws. Synovial fibroblasts were isolated from the arthritis knee joints of DBA/1J mice. These cells expressed type I interleukin 1 (IL-1) receptor constitutively and produced large amounts of IL-6 in response to IL-1 in vitro. Enhanced production of IL-1 was also detected at the arthritis paws. These results suggest that the elevated IL-6 in sera may be associated with the overproduced IL-6 in response to the increased IL-1 at the arthritic joints. Serum IL-6 may be a useful parameter for monitoring disease activity. PMID- 8365824 TI - Involvement of central opioidergic and nonopioidergic neuroendocrine systems in the suppressive effect of acupuncture on delayed type hypersensitivity in mice. AB - The effect of a single treatment of electroacupuncture (Acu) at early or late stages of the efferent phase on 2, 4, 6-trinitrochlorobenzene (TNCB)-induced delayed type hypersensitivity (DTH) was studied in intact and hypophysectomized (HPX) mice. Acu (2.5 Hz, 15 min) applied to the acu-point equivalent to GV4 at 0, 3, 18 or 21 h after TNCB challenge induced significant suppression (45-73%) of the maximal extent of ear swelling at 24 h after TNCB challenge. An immunosuppressive and antiinflammatory drug, prednisolone 10 mg/kg i.p., also suppressed the DTH to the same extent. Pretreatment with intracisternal injection of naloxone hydrochloride (2 micrograms) significantly blocked the Acu-evoked DTH suppression when Acu treatment was done at 0 or 3 h. On the contrary, naloxone did not block the effect of Acu treatment given at 21 h. In order to examine the potential involvement of the pituitary in the suppression of DTH by Acu, the DTH reaction was examined in HPX mice. Acu failed to produce suppressive response in the HPX mice unless given at 0 h. These findings indicate that Acu treatment at acu-point GV4 during the efferent phase of induced DTH can suppress the DTH through central opioidergic or nonopioidergic systems. The pituitary is apparently pivotal in this immunosuppression and it is suggested that the DTH suppression by Acu may be mediated via activation of the neuroendocrine system. PMID- 8365825 TI - Immunosuppressive action of cyclophosphamide in mice: contribution of some factors to determination of strain differences. AB - Mechanisms of strain differences in susceptibility to cyclophosphamide (CP) has been investigated with BALB/c, DBA/2, CC57BR, and C57BL/6 mice. It was shown that the final immunosuppressive effects of CP is a result of a combination of such factors as the level of CP alkylating metabolites in the bloodstream and the sensitivity of the target cells to antiproliferative action of these metabolites. The importance of the immune status peculiarities has been discussed. PMID- 8365826 TI - Effect of a novel anti-rheumatic drug, TA-383, on type II collagen-induced arthritis--suppressive effect of TA-383 on interleukin 6 production. AB - We have evaluated the effect of a novel anti-rheumatic drug, cis-2-(4 chlorophenyl)-4,5-diphenyl-2-imidazoline hydrochloride (TA-383), on type II collagen (CII)-induced arthritis in DBA/1J mice. Treatment with TA-383 (0.4 mg/kg/day) from the day of immunization with CII strongly suppressed the arthritic responses. Increased serum interleukin 6 (IL-6) level was lowered in parallel with the effect. Effect of TA-383 on IL-6 production was examined in vitro. TA-383 inhibited the production of IL-6 by murine synovial fibroblasts stimulated with recombinant interleukin 1 (IL-1) beta in a dose-dependent manner (0.1-10 microM). Neither the general protein synthesis nor the expression of type I IL-1 receptor was affected by TA-383. The results show that TA-383 possesses an inhibitory activity on IL-6 generation and suggest that the effect may partly contribute to the anti-arthritic effect of TA-383. PMID- 8365827 TI - Effect of immunomodulators pyrimethamine and cimetidine on immunosuppression induced by sulfur mustard in mice. AB - Despite extensive world-wide research no effective therapy has been devised for the treatment and cure of patients exposed to sulfur mustard (S-M). A severe suppression of the immune system still remains the major cause of opportunist infections, septicemia and death in patients injured by S-M. In this report we present a model of S-M contamination in mice which is suitable for immunomodulation studies. Results show that differing doses of S-M caused an overall suppression of the immune response to SRBC as indicated by agglutination titers, (DTH) tests, spleen histology and spleen weight indices. In the second stage two immunomodulating agents; pyrimethamine and cimetidine were employed and their effectiveness in augmenting immune responses after S-M induced immunosuppression was evaluated. Pyrimethamine, at all doses employed, enhanced antibody titers to SRBC, augmented DTH responses, and restored splenic follicles as compared with controls only exposed to S-M. Cimetidine augmented antibody titers and enhanced DTH responses at doses of 10 and 15 mg/kg as compared with controls. At a dose of 5 mg/kg cimetidine did not exhibit any effect on titers or DTH responses. Histological studies revealed that cimetidine restored splenic follicles and increased macrophage numbers and phagocytic activity at all three doses. Spleen weight indices were not augmented by either drug. These data provide evidence that immunomodulating drugs may prove effective in countering the immunosuppressive effects of S-M. PMID- 8365828 TI - Anti-CD3-induced T-cell activation--II. Effect of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD). AB - An in vivo model was used to examine the effect of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) on various parameters of T-cell-activation. In this model, the hamster anti-mouse monoclonal antibody 145-2C11 (anti-CD3) to the CD3 portion of the murine T-cell receptor was injected into both rear footpads of female C57B1/6 mice and the draining popliteal and inguinal lymph node cells (LNC) were removed 24 h later. Cyclosporin A (CsA) was included as a known immunosuppressive control. As expected, CsA (50 mg/kg, i.p.) suppressed anti-CD3-induced proliferation, IL-2-driven 3H-TdR incorporation, and IL-2R expression. In contrast, TCDD unexpectedly enhanced anti-CD3-induced 3H-TdR incorporation. Flow cytometric analysis showed that TCDD treatment increased the percentage of both CD4+ and CD8+ cells cycling in S and G2M. LNC from TCDD-treated mice also had enhanced 3H-TdR incorporation when cultured in the presence of a saturating amount of exogenous mIL-2. TCDD did not significantly alter the percent positive or the number of IL-2 receptors (IL-2R) on either CD4+ or CD8+ cells when examined at several time points after anti-CD3 treatment. Both the kinetics and extent of anti-CD3-induced down-modulation of CD3 expression on CD4+ and CD8+ cells was unaffected by TCDD. TCDD alone did not result in enhanced 3H-TdR incorporation, cell cycling or IL-2R expression. Therefore, TCDD appears to be targeting T-cells that are undergoing activation rather than resting cells. The strength of the anti-CD3 model is evidenced by the fact that two known immunosuppressive compounds (CsA and TCDD) have distinct and opposite effects on T-cell activation. These findings suggest that the mechanism(s) by which CsA and TCDD impair T-cell function are different. PMID- 8365829 TI - Effects of acute inhalation of albuterol on submaximal and maximal VO2 and blood lactate. AB - The acute effects of inhaled albuterol, a selective beta-2 adrenergic agonist, on measures of endurance cycling performance and pulmonary function were assessed in 21 competitive road cyclists. A 5 step methacholine challenge revealed all cyclists to be non-asthmatic. Albuterol (A) total dose 360 micrograms or a saline placebo (P) was administered by inhaler, in 4 metered doses of 90 micrograms each, 15 minutes before cycle ergometry exercise. Heart rate, whole blood lactate, perceived exertion and VO2 were determined at the submaximal workloads of 150, 200, 225, 250, 275, 300 watts and at max. Pulmonary function tests determining forced vital capacity, forced expiratory volume during the first second of expiration, forced mid-expiratory flow and maximal voluntary ventilation were performed prior to and 10 minutes after inhalation; and 5, 10 and 15 minutes after termination of the exercise protocol. Heart rate was significantly greater during the A compared to the P treatment at 200 (150.8 +/- 2.5 vs 146.7 +/- 2.8 beats per minute), 225 (159.7 +/- 2.4 vs 154.6 +/- 2.7 beats per minute) and 250 watts (166.9 +/- 2.4 vs 164.4 +/- 2.6 beats per minute). Whole blood lactate was significantly greater during the A compared to the P treatment at 275 watts (4.7 +/- 0.3 vs 4.2 +/- 0.4 mmol.l-1). No other significant differences were found between the 2 treatments at any time point. These data indicate that the acute effect of albuterol inhalation at twice the recommended dosage has no positive effect on endurance performance measures or pulmonary function in athletes who are not asthmatic. PMID- 8365830 TI - Body composition and maximum alactic anaerobic performance during a one month stay at high altitude. AB - Prolonged altitude exposure usually leads to considerable weight loss of which a large part is from muscle tissue. This loss reduces maximum alactic anaerobic muscle power. It was hypothesized that most of the weight loss may simply be the result of malnutrition due to lack of palatable food in an uncomfortable environment. To test this hypothesis eight healthy male subjects (age 33.7 +/- 4.6 S.C. yr), well acclimatized to prevent symptoms of acute mountain sickness, were exposed for 4 weeks to an altitude of 5050 m with access to a large choice of palatable food in comfortable conditions. Body weight (with a scale), body composition (from skinfolds), arm muscle plus bone cross-sectional area (Am + b) and muscle plus bone leg volume (Vm+b) (from skinfolds and circumferences), maximum voluntary contraction force of the elbow flexors (MVC, with a load cell) and maximum jumping height (Hmax, on a platform) were measured before departure (SL) and in the first (ALT1), second (ALT2) and fourth week (ALT4) of their altitude sojourn. Three-day dietary records were obtained at SL and at ALT4. Body mass had decreased significantly at ALT2 (-3.8%) and at ALT4 (-4.6%) likely reflecting changes in body water homeostasis. No changes were found in %fat, Am+b, Vm+b, MVC or Hmax. Average dietary intake at SL was 8.96 +/- 1.45 MJ and had increased to 13.59 +/- 3.07 MJ at ALT4. In conclusion, up to an altitude of 5050 m loss of body mass from fat and muscle tissue, and hence impairment of maximum anaerobic muscle power (alactic) appears to be avoidable by food intake matched to energy expenditure. The latter may be achieved simply by proper acclimatization, sufficient comfort and availability of palatable food. PMID- 8365831 TI - Effect of water temperature on exercise-induced maternal hyperthermia on fetal development in rats. AB - The objective of this study was to determine if water temperature influenced exercise-induced hyperthermia in swim-trained pregnant rats and the resulting fetal development. Pregnant Sprague-Dawley rats with 6 weeks pre-pregnancy training were exercised daily from day 1 to day 18 of gestation in water that was 34.6 +/- 0.4 degrees C (Cool Water Swimmers--CWS) or 37.6 +/- 0.1 degrees C (Warm Water Swimmers--WWS), for one hour/day. During this time period another group of pregnant rats was immersed to the neck in warm water (37.6 +/- 0.2 degrees C) (Warm Water Controls--WWC). On day 19 of gestation all animals were sacrificed and fetal development assessed. Maternal exercise in warm water elevated maternal body core temperature by 2.3 +/- 0.1 degrees C above resting values, with an increase in fetal abnormalities compared to the same exercise intensity in cool water. Fifty-eight percent of the abnormal fetuses and 60% of the resorption sites were found in the WWS group. Of the abnormalities determined, 65% were from the WWS group and 45% of these fetuses showed micrencephaly. Results suggest cool water may regulate maternal body temperature during swimming exercise and that swimming in warm water should be avoided during gestation because of potential teratogenic effects. PMID- 8365832 TI - Mechanical energy assessment with different methods during running. AB - In order to compare mechanical measurements obtained with force platforms, film analysis and a kinematic arm, a sprint runner and a long distance runner were asked to run at different constant velocities ranging from 2.5 m.s-1 to 5.5 m.s 1. The external (EW) mechanical work reflected in the motion of the center of mass (CM) of the subject was computed using force platforms, film analysis and a kinematic arm. The differences observed on EW computations ranged from 12.3% +/- 2.5% (film analysis vs kinematic arm) to 1.4% +/- 1.8% (kinematic arm vs force platforms). These differences could be explained by (i) film analysis inaccuracy and (ii) vertical kinematic arm oscillations. Furthermore, the data obtained with a multisegment model confirm that the large discrepancy found in the literature on running efficiency is not mainly due to the accuracy of the force and/or displacement measurements, but to the different methods of estimation of the mechanical power produced by the muscles. It is suggested that the kinematic arm principle can be applied successfully for computation of CM displacements and CM energy changes during running. PMID- 8365833 TI - Fast twitch fibres may predict anaerobic performance in both females and males. AB - The aim of the present study was to compare males and females with similar training backgrounds regarding the relationship between anaerobic performance and muscle characteristics and to test whether any of the analysed expressions of muscle characteristics could predict some of the difference in anaerobic performance between sexes. Subjects performed 30 s all-out sprints on a bicycle ergometer (Wingate test) and needle muscle biopsies were taken at rest. Peak and mean power were respectively 44% and 48% higher in males than in females. Activity of total lactate dehydrogenase (LD) was 33% higher and of M subunit of LD 38% higher in males. Anaerobic performance was directly related to the proportion of type II fibres, the relative M subunit activity or the activity of PFK in both males and females and the higher M subunit activity in males could predict some of the sex difference in anaerobic performance. It is suggested that anaerobic performance is directly related to fast contractile or/and anaerobic metabolic properties of skeletal muscle with no sex difference in this relationship. The difference in anaerobic performance between the sexes may partly be related to the sex difference in anaerobic metabolic properties of skeletal muscle. PMID- 8365834 TI - Fixed time versus fixed distance protocols for the blood lactate profile in athletes. AB - Laboratory studies of blood lactate accumulation often use a fixed time protocol to define the onset (4 mM) of blood lactate accumulation (OBLA) or other indices of blood lactate concentration. For practical reasons, field studies with athletes often use a fixed distance protocol to accomplish the same goal. Whether these variations of protocol are comparable has not been established. We studied 10 subjects in the laboratory during fixed time (4 minute) and fixed distance (2 km) exercise protocols on a racing bicycle attached to a wind load simulator. The fixed distance studies required 3-6 minutes to complete. We also studied the subjects during fixed distance (2 km) rides in the field. In the laboratory there were no systematic differences in the velocity (34.3 4.6 vs 34.2 +/- 4.6 km.hr 1), VO2 (2.78 +/- 0.60 vs 2.84 +/- 0.62 liters.min-1), or heart rate (159 +/- 16 vs 155 +/- 14 beats.min-1) at OBLA in the fixed time vs fixed distance protocols. The correlation coefficients for velocity (r = 0.97), VO2 (r = 0.97) and heart rate (r = 0.94) further indicate the similarity of results. In the field study there was a significant difference in velocity (29.9 +/- 4.8 vs 34.2 +/- 4.6 km.hr-1) but not heart rate (155 +/- 18 vs 155 +/- 15 beats.min-1) at OBLA versus the fixed distance laboratory study. The correlations for velocity (r = 0.47) and heart rate (r = 0.93) support these data. The results suggest that the practical modification of the lactate profile technique of using fixed distance versus fixed time exercise stages does not systematically influence the outcome, at least for exercise stage durations approximating 4 minutes. PMID- 8365835 TI - Oxygen uptake, heartrate and blood lactate responses to the Chito-Ryu Seisan kata in skilled karate practitioners. AB - To evaluate the efficacy of Seisan kata as an aerobic power training mode, four male (28.5 +/- 4.2 y) Chito-Ryu karate black belt practitioners did kata continuously for 10 min. In separate sessions the kata (formal, organized movement sequences) were done at rates of 1 (PACE) and 2 (FAST) kata "cycles" per minute. Heartrate (HR) and VO2 were monitored continuously during the sessions. VO2 during the PACE and FAST sessions averaged 73 +/- 3 and 94 +/- 2% of leg cycling VO2peak, respectively. The corresponding HRs were 93 +/- 6 and 101 +/- 3% of HRmax (leg cycle test). PACE and FAST post-exercise blood lactates were 12 +/- 4 and 22 +/- 6%, respectively, of the maximal leg cycle test values. These data indicate that karate kata can be used as an effective and specific means for training aerobic power in karate practitioners. PMID- 8365836 TI - The effect of light, moderate and severe bicycle exercise on lymphocyte subsets, natural and lymphokine activated killer cells, lymphocyte proliferative response and interleukin 2 production. AB - The purpose of the present study was to evaluate the effect of acute bicycle exercise at different exercise intensities on the immune system. Six healthy volunteers exercised on a bicycle ergometer for 1 h at 25%, 50% and 75% of VO2max with an interval of 2 to 3 weeks. Blood samples were collected in the basal state, at the end of exercise and 2 h later. The absolute concentrations of all lymphocyte subsets increased during and fell after exercise at 50% and 75% of VO2max, but did not change significantly at 25% of VO2max. However, at all exercise levels, the percentage of CD3+ blood mononuclear cells decreased due to a decline in the fraction of CD4+ cells. This decline was most pronounced at 75% of VO2max. The fraction of NK cells expressing either the CD16 or the CD56 marker increased during exercise and declined to prevalues 2 h later, however the changes were most pronounced at 75% of VO2max. The natural killer (NK) cell and lymphokine activated killer (LAK) cell activities (lysis per fixed number of mononuclear cells) were increased during all exercise intensities, but were only suppressed below basal levels after exercise at 75% of VO2max. Indomethacin in vitro abolished the post-exercise suppression of NK cell activity and the proportion of CD14+ monocytes increased 2 h after exercise only at 75% of VO2max. These findings indicate that after exercise NK cell function is inhibited by prostaglandins released by monocytes. During exercise at 50% and 75% of VO2max the proliferative response of blood mononuclear cells (BMNC) following stimulation with phytohaemagglutinin A (PHA) decreased, whereas that following stimulation with interleukin-2 (IL-2) was enhanced. The IL-2 production by BMNC in vitro was markedly decreased during and after exercise at 75% of VO2max and this inhibition could be abolished by indomethacin in vitro. In conclusion, the response of the immune system to exercise depends on exercise intensity. In essence, the response is enhanced during exercise, however, after heavy exercise it is suppressed due to an increased level of prostaglandins produced by the elevated number of monocytes. PMID- 8365837 TI - Functional and morphological adaptations following four weeks of knee immobilization. AB - Immobilization of the knee as part of the treatment in bone or joint lesions leads to atrophy and consequently loss of functionally. In patients this atrophy and loss of functionality is difficult to quantify because of interfering symptoms and missing baseline data. In the present study structural and functional changes in thigh muscles were examined in eight healthy volunteers of whom one leg was immobilized in a cast for four weeks. Quadriceps cross-sectional area determined with computed tomography was 21% +/- 7% diminished after four weeks immobilization (p < 0.05). Muscle biopsies from the musculus vastus lateralis revealed an 16% decreased fiber diameter (p < 0.05) and no significant shift in fiber types. Isokinetic strength measurements of knee extensors and flexors demonstrated a fall in peak torque of 53% +/- 9% and 26% +/- 13% at an angular velocity of 60 deg.s-1 (p < 0.01). Aerobic power in one-leg-cycling exercise was not significantly affected, but isokinetic quadriceps endurance work decreased from 9.1 kJ to 5.6 kJ (p < 0.05). Despite the fall in quadriceps performance the subjects had only minor functional complaints for a few days. It is concluded that immobilization of the knee is an important factor in the development of thigh muscle atrophy in patients and should therefore be diminished as much as possible. PMID- 8365838 TI - Soreness in lower extremities and back is reduced by use of shock absorbing heel inserts. AB - Soccer referees participating in large soccer tournaments may develop overuse injuries. In this study the effect of shock absorbing heel inserts in the incidence of soreness was investigated. Forty-eight referees were randomly selected to wear shock absorbing heel inserts (SAH) in the 5 day-tournament, while 43 referees were the control group. A daily questionnaire inquiring about complaints from the locomotive system was completed for each referee and in case of any soreness they were examined by doctors to document and classify the anatomical site. Calf, thigh, back, achilles tendon and knee were the most common localizations of overuse symptoms. The incidence of soreness in achilles tendon, calf and back were significantly reduced by the use of (SAH) inserts. PMID- 8365839 TI - Can experimental immobilization studies predict the clinical process after orthopedic surgery? PMID- 8365840 TI - Pyeloform-aided percutaneous litholapaxy. I. Case study. AB - To remove multiple calyceal stones percutaneously is not a simple task. During the act of dilating the pierced channel the stones are apt to drift away towards other parts of the renal cavitary system. For avoidance we recommend the use of Pyeloform, a bicomponent synthetic compound in which chemical reaction between the two substances produces a gel-like matter. This permits the stones partly to be embedded, partly to be fixed against the risk of displacement. Described is the effect of Pyeloform in the removal of multiple calyceal stones. PMID- 8365841 TI - Massive haematuria from a renal haemangioma with concomitant ureteropelvic junction obstruction. AB - A two centimeter left capillary renal haemangioma caused massive haematuria in a 27-year-old male with left hydronephrosis and nephrolithiasis. Nephrectomy for life threatening haemorrhage was performed. Diagnostic algorithms for the evaluation of adult onset gross haematuria and "essential" haematuria with a review of the current literature are presented. PMID- 8365842 TI - The significance of cystoscopy for the diagnosis of urothelial tumour. AB - Authors have studied the aetiology of asymptomatic microhaematuria on the basis of complete urologic examinations including cystoscopy, excretory urography, ultrasound, urinalysis and urinary cytology. In 10 out of 422 patients transitional cell carcinomas of the urinary bladder were found. Bladder cancer was the most common malignancy among the lesions found by our evaluation of patients with microhaematuria. We conclude that cystoscopy should be an essential part in the aetiological evaluation of microscopic haematuria. PMID- 8365843 TI - Primary vesicoureteral reflux in children under one year of age: the case for conservative management? AB - The natural course of reflux nephropathy was evaluated in children who have been diagnosed for primary vesicoureteral reflux already during the first year of life. The retrospective study in 103 patients (163 refluxive renal units) revealed that 80% of all children in this age group were boys. Scarring at the time of diagnosis was evident in 29% of the cases, compared to a rate of 20% in our whole reflux population. New scarring occurred in 17 patients (18%): 63% of the children had high grade refluxes (IV and V). The rate of spontaneous resolutions was 61% and even grade V refluxes showed a spontaneous cessation in 40% of the cases. These data indicate a high overall spontaneous cure rate in young children, but underline the importance of selecting those patients with already scarred kidneys and recurrent urinary tract infections for an early operation since they are not likely to show a spontaneous resolution of reflux. PMID- 8365844 TI - Periureteric effects of electromagnetic shock waves. AB - The effect of electromagnetic shock waves on the ureter and periureteric soft tissue was investigated in 10 patients who underwent extracorporeal shock wave lithotripsy (ESWL) for lower ureteric stones. Seven patients were males and 3 females, their ages ranged between 15 and 52. The number of shock waves applied varied between 3000 and 6000, at a mean of 19 kV. The patients were examined after their first ESWL. Magnetic resonance imaging (MRI) was performed within 6 hours of treatment by a Magnetom 1 Tesla Unit. No haematoma, fluid collection or abnormality was detected in the periureteric space, muscle or surrounding structures by MRI. Although subcapsular, intra- or perirenal haematomas can be observed in patients with kidney stones treated with ESWL, it appears to be safe for lower ureteric stones. PMID- 8365845 TI - Primary bladder pheochromocytoma without hypertension. AB - A case of urinary bladder pheochromocytoma is presented. Although urinary norepinephrine concentration was high, the patient was normotensive and no blood pressure fluctuations occurred after micturition. PMID- 8365846 TI - Rhabdomyosarcoma of the urinary bladder in an adult. AB - Primary bladder rhabdomyosarcoma is very rare in adults. We report a 76-year-old man who underwent partial cystectomy with postoperative radiotherapy and had a recurrence 6 months after the operation. PMID- 8365847 TI - Primary non-Hodgkin lymphoma of the prostate gland. AB - We present a case of non-Hodgkin lymphoma of the prostate referring to an 86-year old male, who was admitted with a history of urine retention of 10 days' duration. The symptoms and signs were compatible with a diagnosis of benign prostatic hypertrophy, with no preoperative evidence of malignancy. Following transvesical prostatectomy, immunocytochemical analysis of the specimen showed a highly malignant non-Hodgkin lymphoma of the large immunoblastic B-cell type, with a cIgM (kappa) phenotype. PMID- 8365848 TI - Orgotein in the treatment of plastic induration of the penis (Peyronie's disease). AB - Eighteen patients with Peyronie's disease have been treated with the anti inflammatory metalloprotein Orgotein, which exhibits a pronounced superoxide dismutase activity. Only patients with severe symptoms were selected. The drug was injected monthly into the indurated areas of the penis. Marked improvement was noted, especially regarding the loss of pain on erection. Only one adverse reaction has occurred. PMID- 8365849 TI - Use of intraoperative venography in varicocelectomy. AB - We performed intraoperative venography in 22 patients, of whom 8 had persistent varicocele. The results of the outpatient procedure were encouraging. PMID- 8365850 TI - Problems unique to microsurgical epididymovasostomy. Comparison of four techniques in a laboratory rat model with review of the literature. AB - The new microsurgical techniques, tubule and loop intussusception, are compared to end-to-end and side-to-end in an experimental rat model. Sixty adult male Sprague-Dawley rats were operated on bilaterally under the same conditions. The four microsurgical techniques differ in approach to the inner mucosal layer, while the outer adventitial layer was sutured similarly in all cases. Luminal patency was checked 3 months postoperatively. There was no statistically significant difference in the patency rate among these four techniques (P = 0.3196). However, the incidence of macroscopically (P < 0.001) and microscopically (P < 0.01) detected spermatic granulomas was highly significant despite the optimum size match for each method. We found side-to-end techniques superior and easier to perform than end-to-end. The loop intussusception offers the highest patency rate (100%) with the lowest incidence of spermatic granuloma (10%). It was, therefore, concluded that selection of surgical technique is of utmost importance for durability of anastomosis. PMID- 8365852 TI - Nerve conduction velocities and hair concentrations of trace elements in haemodialysis patients. AB - Nerve conduction velocities and hair concentrations of trace elements were studied in 19 male patients with chronic renal failure undergoing haemodialysis. Both motor and sensory nerve conduction velocities were significantly lower in haemodialysis patients as compared to controls (p < 0.001). Calcium and aluminium concentrations were significantly higher in patients (p < 0.01), however, vanadium and arsenic levels were significantly lower in patients (p < 0.01). In concentrations of copper and zinc there was no significant difference between patients and controls. There were no significant correlations between hair concentrations of trace elements and nerve conduction velocities except between calcium concentration and sensory nerve conduction velocity. These facts suggest that nerve conduction velocities are not influenced by changes of trace element concentrations in hair in patients with chronic renal failure undergoing haemodialysis. PMID- 8365851 TI - Acute glomerulonephritis associated with acute pneumococcal meningitis. A case report. AB - The frequency of complications in pneumococcal infections has decreased after the extensive use of antibiotics. However, pneumococcal postinfectious acute glomerulonephritis is rarely seen. A case of acute pneumococcal meningitis with acute glomerulonephritis which shows signs of nephritic and nephrotic syndrome is presented in this report. PMID- 8365853 TI - Correction of anaemia in haemodialysis patients with recombinant human erythropoietin. AB - We administered recombinant human erythropoietin (r-hu EPO) to 18 anaemic patients with end-stage renal disease who were undergoing haemodialysis. The recombinant human erythropoietin was given intravenously three times weekly after dialysis, and transfusion requirements, haematocrit, ferrokinetic, reticulocyte responses and urea, creatinine and potassium kinetics were monitored. Over a range of doses between 50 to 90 units per kilogram of body weight, dose-dependent increases in effective erythropoiesis were noted. Of 18 patients receiving effective doses of recombinant human erythropoietin, none needed transfusion any longer and in 2 the haematocrit increased to 35%. Along with the rise in haematocrit, four patients had an increase in blood pressure, and the majority had increases in serum potassium, fibrinogen, leucocyte and reticulocyte counts. Except for transiently increased transaminase levels in one patient, no other organ dysfunction or toxic effect was observed. These results demonstrate that recombinant human erythropoietin is effective, can eliminate the need for transfusions with risks of immunologic sensitization, infection and iron overload, and can restore the haematocrit to normal levels in many patients with anaemia of end-stage renal disease. PMID- 8365854 TI - Renal failure and uraemia leading to the diagnosis of prune belly syndrome in a 34-year-old man. AB - The case of a 34-year-old male is reported, who was transferred to the Regional Medical Center in Wels in an uraemic state and subsequently was diagnosed as having prune belly syndrome. Surprisingly, his past history revealed no serious health problems until 6 months before admission. Furthermore, some interesting aspects of the prune belly syndrome such as the controversial views regarding pathogenesis and treatment are briefly discussed. PMID- 8365855 TI - [Vasculitis. Nomenclature and diagnosis]. PMID- 8365856 TI - [Coronary vasculitis]. PMID- 8365857 TI - [Significance of vasculitis in diseases of rheumatic origin]. PMID- 8365858 TI - [Vasculitis of the skin. Significance for internal medicine]. PMID- 8365860 TI - [Neurologic aspects of vasculitis]. PMID- 8365859 TI - [Vasculitis of the kidney]. PMID- 8365861 TI - [Indurating soft tissue swelling, eosinophilia and increased blood sedimentation rate]. PMID- 8365863 TI - [Comments on the contribution by X. Baur and J. Ammon. Diagnosis of allergy]. PMID- 8365862 TI - [Occasionally patients treated with thrombocyte aggregation inhibition with acetylsalicylic acid also must be treated with non-steroidal antirheumatic drugs]. PMID- 8365865 TI - Steer kids away from smoking. PMID- 8365864 TI - [Stomach ulcer and duodenal ulcer]. PMID- 8365866 TI - Physicians must remain committed to beneficial reform. PMID- 8365867 TI - Health care should be subject to cost constraints. PMID- 8365868 TI - Clozapine shows promise in schizophrenia treatment. AB - Clozapine represents the first significant advance in the pharmacotherapy of schizophrenia since development of phenothiazine antipsychotic drugs in the 1950s and 60s, yet only about 10% of potential patients nationwide are taking the medication. PMID- 8365870 TI - Therefore choose life. PMID- 8365869 TI - Consideration, mutual respect are vital in the workplace. PMID- 8365871 TI - The evolution of hospital ethics committees. PMID- 8365872 TI - Intraoperative transesophageal echocardiography. AB - Intraoperative echocardiography in patients undergoing cardiac surgery was first described in 1972. Interest in intraoperative echocardiography has grown in recent years due to the extensive information provided by 2-dimensional (2-D) and color-flow Doppler imaging via the transesophageal approach. The value of this technique also has been verified in large clinical studies involving patients undergoing cardiac surgery. Intraoperative transesophageal echocardiography (TEE) is very useful in preoperative formulation of surgical plans and in immediate post-operative assessment of surgical results in patients undergoing valve surgery. PMID- 8365873 TI - Primary caffeine dependence: a case report. AB - We present a case of primary caffeine dependence based on the exclusive use of over-the-counter caffeine tablets. Caffeine has recently undergone scrutiny as a co-morbid risk factor with other substance dependencies, and in other medical and psychiatric conditions. Caffeine withdrawal also is briefly discussed with attention given to personality factors and the use of nicotine. Although caffeine generally is considered safe in usual doses, it is a substance potentially able to result in serious dependence. We cite a case which also illustrates that a supportive inpatient milieu may be necessary in order to interrupt a cycle of heavy caffeine use resulting in marked dependence. PMID- 8365874 TI - Testicular microlithiasis: ultra sound appearance. AB - Testicular microlithiasis is a diffuse, benign condition involving both testicles without architectural distortion. Multiple, bright echoes are present on ultrasound examination which rarely cause shadowing. Many associated conditions have been reported in patients with this entity. As this is a benign entity, knowledge of its appearance and associated conditions to prevent unnecessary surgery is important. PMID- 8365875 TI - Dedication of the Robert J Emrick MD Library. PMID- 8365876 TI - [The role of eosinophilic granulocytes for the pathogenesis of atopic dermatitis /neurodermatitis. Eosinophilic products as markers of disease activity]. AB - Recent data provide increasing evidence for an immunological basis of atopic dermatitis (AD). Atopyspecific helper T cells (Th2-like T cells) may play a pathogenic role by producing and releasing cytokines that are relevant for the allergic inflammation, such as IL-4, IL-5 and other growth factors. It is suggested that eosinophils play a major role as effector cells mediating the pathogenetically important late-phase reaction, which is associated with significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to enhanced susceptibility of these cells to distinct stimuli, such as IL 5. Toxic proteins, such as eosinophil cationic protein (ECP), which are contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by exerting their direct immunomodulatory effects. A pathogenic role of eosinophils in AD is further supported by the detection of these proteins in eczematous skin of the patients. Furthermore, recent data indicate a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease both in the clinical score and in serum ECP levels. These data clearly indicate that activated eosinophils are involved in the allergic inflammatory process in AD. Therefore, modulation of eosinophil activation could be an important pharmacologic modality for the treatment of AD in the future. PMID- 8365877 TI - [Polypoid malignant melanoma. An aggressive, seldom observed variant of nodular malignant melanoma]. AB - We describe a 54-year-old man with a polypoid melanoma. The tumour had developed within 1 year. Physical examination showed an eroded pedunculated nodule approximately 2.5 x 3 cm in size. Histopathology revealed a pedunculated, sharply demarcated tumour with an eroded surface; it was composed of atypical melanocytes in sheets and nests. Physical examination 11 months after excision of the tumor with 3-cm safety margin disclosed no evidence for enlarged lymph nodes or cutaneous metastases. No metastases were seen on computer tomography. To our knowledge, this patient represents the first case of polypoid melanoma reported in the German literature. PMID- 8365878 TI - [Adamantiades-Behcet disease. Therapeutic administration of systemic recombinant interferon-alpha-2a]. AB - The effect of systemic recombinant interferon alpha-2a (rIFN-alpha-2a) on the mucocutaneous lesions in Adamantiades-Behcet's disease was assessed in ten patients with the mucocutaneous type of the disease. rIFN-alpha-2a was applied subcutaneously at a dose of 9 x 10(6) IU three times a week for 6 months. Five patients showed a significant reduction in the number, severity, duration and frequency of their mucocutaneous lesions during the treatment compared with the pretreatment phase, whereas in two patients a complete remission and in three patients a partial remission was achieved. In two patients, one with complete and one with partial remission, recurrence of the cutaneous symptoms occurred shortly after discontinuation of the treatment. Renewed administration of rIFN-alpha-2a again led to remission of the symptoms. In another patient with initial partial remission followed by exacerbation, interferon alpha antibodies were detected and the patient responded again when 15 x 10(6) IU rIFN-alpha-2a was administered three times a week. Three patients did not show any change in the characteristics of their lesions, while two patients experienced progression of their disease during treatment. Side-effects were generally mild and well tolerated, but the treatment was discontinued earlier than planned in one patient because of fatigue, myalgia, hypotonus and diarrhoea. Since the classical treatments are generally unsatisfactory, the results of the present study justify the administration of systemic rIFN-alpha-2a in the treatment of the mucocutaneous type of Adamantiades-Behcet's disease. PMID- 8365879 TI - [Imaging subcutaneous atrophy in circumscribed scleroderma with 20 MHz B-scan ultrasound]. AB - The technique of 20-MHz B-scan sonography is non-invasive and allows quantification of the different compartments of the skin. Seven patients with atrophic linear circumscribed scleroderma and one patient with guttate circumscribed scleroderma were examined by ultrasound. All patients were found to have a total or subtotal loss of subcutaneous fatty tissue, whereas the thickness of the dermis remained almost unchanged. These findings should lead to further investigation of the pathophysiological mechanism involved in subcutaneous atrophy in circumscribed scleroderma. PMID- 8365880 TI - [Lupus erythematosus discoid-like dermatosis in a carrier of septic granulomatosis]. AB - We present a clinically atypical case of discoid lupus erythematosus in the mother of a boy with chronic granulomatous disease. In this disorder, the phagocytes are unable to produce superoxide anion to degrade incorporated microorganisms. In addition to a discoid lupus erythematosus-like skin disease, recurrent stomatitis aphthosa, hidradenitis suppurativa and Raynaud phenomenon are markedly associated with heterozygote carriers of chronic granulomatous disease. Based on this conspicuous association, diverse models concerning the pathogenesis of lupus erythematosus are discussed. PMID- 8365881 TI - [Current therapeutic possibilities in cutaneous larva migrans]. AB - The recommendations for the treatment of cutaneous larva migrans are not uniform, and the recommended methods are neither always available nor always effective. If only the skin is affected, primarily topical therapy is indicated. Topical thiabendazole combines efficacy with missing systemic side-effects. In Germany the pure substance has to be used or Mintezol tablets must be purchased from abroad. Topical mebendazole and freezing with liquid nitrogen are less effective and involve side-effects. If topical treatment fails, systemic therapy is required. The recognized treatment with oral thiabendazole (2 days) is associated with numerous side-effects. There are now two new, safer drugs that should be preferred: albendazole (400 mg/day for 3 days), available in Germany as Eskazole, or ivermectin (single dose of 200 micrograms/kg). The latter can be ordered from the manufacturer under the trade name of Mectizan. PMID- 8365882 TI - ["Baboon syndrome". A particular manifestation of hematogenous contact reaction]. AB - We report on a 52-year-old patient with a typical manifestation of a haematogenous contact reaction. The characteristic distribution of light-red erythema predominantly located in the major flexural areas of the extremities and on the buttocks was consistent with the diagnosis of "baboon syndrome." The term derives from the skin lesions, which are compared to the red gluteal region of the baboon. An allergic type-IV reaction to systemically administered allergens probably underlies lesions of this type. In our case the baboon syndrome had been induced by amoxicillin. So far, mercury, nickel, ampicillin, and heparin have been reported as causes of baboon syndrome. PMID- 8365883 TI - [Chronic bullous dermatosis in childhood (linear IgA dermatosis)]. AB - A 5-year-old boy presented with disseminated, partly grouped blisters indicative of chronic bullous dermatosis of childhood (CBDC) following a gastrointestinal infection 2 weeks earlier. CBDC has long been differentiated from adult linear IgA disease. Clinical and laboratory studies revealed substantial clinical and immunological overlap between the two blistering disorders, whereas recent investigations suggest heterogeneity of the target antigen involved. Pathohistological and immunofluorescence-microscopical characteristics of a subepidermal blister and linear IgA and granular C3 deposition at the basement membrane together with the typical history and clinical signs were decisive in the differential diagnosis. The disease promptly cleared up after daily administration of 16 mg methylprednisolone-21-acetate tapering and 25 mg dapsone. Immunohistological detection of collagen IV at the base of a blister made it possible to localize the split above the lamina densa. The demonstration of collagen IV stresses the importance of immunodermatopathology in the differential diagnosis of subepidermal blistering diseases. PMID- 8365884 TI - [Striped nail pigmentation with Hutchinson signs in a boxer]. AB - We present a 68-year-old male patient, who had had longitudinal melanonychia with Hutchinson sign for 4 years. Melanocytic proliferation was ruled out by biopsy. Friction and pressure had been acting on this patient's nails during boxing for the past 40 years. These mechanical factors are discussed under the entity of "frictional longitudinal melanonychia". In addition, cellular and non-cellular mechanisms for longitudinal melanonychia are reviewed. PMID- 8365885 TI - [The Munich Society of Dermatology. Scientific meeting 6 November 1992]. PMID- 8365887 TI - [Persistent Mongolian spot, nevus of Ota and giant blue nevus: melanoma precursors?]. PMID- 8365886 TI - [Diet in neurodermatitis]. PMID- 8365889 TI - Enter the secret service. PMID- 8365888 TI - [Exudative discoid and lichenoid chronic Sulzberger-Garbe dermatosis ("Oid-Oid disease")--reality or fiction?]. PMID- 8365890 TI - Water. Scots verdict. PMID- 8365891 TI - Slow drip of dilution. PMID- 8365892 TI - Sickle cell. Black counsellors under pressure. PMID- 8365893 TI - Weaning. Any old iron. AB - Gabrielle Palmer takes issue with manufacturers' claims for follow on milks, arguing that they are often 'generous with alarm and economical with the truth'. A balanced weaning diet is the key to preventing iron deficiency anaemia in children. PMID- 8365894 TI - Cause and cure for iron deficiency in toddlers. AB - Iron deficiency is the commonest cause of anaemia in Britain. Maureen B Duggan asks: How does toddler iron deficiency aris? How is it reliably diagnosed? And how can it be prevented in the community? Is iron supplementation of foods, especially of breast milk substitutes and follow-on formulae important in communities at risk? PMID- 8365895 TI - Wealth and the nation's health. AB - Social and economic prosperity to a great extent depend on a healthy population; similarly good health depends on adequate income, writes Clare Blackburn. The government strategy for health promotion outlined most recently in The health of the nation, fails to acknowledge this. Nevertheless health visitors and school nurses cannot ignore the links between health and wealth. PMID- 8365896 TI - Collaboration in coronary heart disease prevention. AB - Health visitors are ideally placed in primary care to offer effective dietary and life-style advice as part of a team approach to coronary heart disease prevention, write Alan Jones et al. Results from a dietary and life-style intervention trial programme suggest that dietitians, who are limited in numbers, should be used as a resource to provide expert dietary advice and training to the more numerous health visitors. In this way CHD risk factor identification can be developed into effective intervention. PMID- 8365897 TI - Health promotion: stepping into the breach--again. AB - Despite government resistance to formal merger, district and family health service authorities (DHAs and FHSAs) are increasingly looking to make joint community nurse appointments to fill evident gaps in general practitioner health promotion services. Cath Jackson highlights two pioneering projects. PMID- 8365898 TI - Disability living allowance: Children can get it too. PMID- 8365899 TI - Recognition. When the music stops. AB - Trade unions can no longer expect NHS employers automatically to recognise their role in negotiating employment terms and conditions on behalf of their members. NHS self-governing trusts are now free to set their own terms and conditions of employment--and to choose with whom they wish to negotiate. Roger Kline outlines the importance of recognition agreements. PMID- 8365900 TI - Student fatigue. PMID- 8365901 TI - Milking the market. PMID- 8365902 TI - The plight of caregivers. AB - The prospect of becoming a primary caregiver is of growing concern for everyone because of the increase in the aging population. The demands of caregiving place caregivers at risk for becoming ill themselves. Nurses are vital in keeping care recipients and their caregivers healthy. This article examines the problems confronting caregivers and suggests means of coping with the additional and unanticipated responsibilities. PMID- 8365903 TI - Tuberculosis: a new threat from an old nemesis. AB - Mycobacterium tuberculosis (TB), which only a few years ago was thought to be under control and soon to be eliminated, has resurfaced as a real threat in the home and community setting. This article discusses TB symptoms, therapies (including a discussion of the drug-resistant forms of TB), prevention and control strategies, and the role of the home healthcare nurse in the surveillance for and management of TB. PMID- 8365904 TI - Implementation of a hepatitis B vaccine program: a how-to guide for home care providers. PMID- 8365905 TI - Love is what we need most. AB - Older people are subjected to increased amounts of stress and isolation as the losses that accompany old age occur. Love is a human need that is especially important for the elderly. PMID- 8365906 TI - Prevalence of sexual harassment among rural community care workers. AB - This study identified the prevalence of sexual harassment and the demographic characteristics of rural, midwestern community care workers (CCWs). To prevent premature institutionalization, community care workers provide home-based assistance that enables elderly persons to remain in their homes. Data were collected from 735 CCWs to determine their demographic characteristics and the prevalence of sexual harassment at the work site. The prevalence portion of the instrument provided data which indicated that 27.8% of the CCWs were harassed on the job and that 15% of the workers were harassed by their elderly client. Demographic characteristics were collected which showed that 94.8% of the CCWs were women, 60.4% were married, and 89.8% were white. Discussion and recommendations drawn from the results of the collected data are included in this article. PMID- 8365907 TI - The "E" word. PMID- 8365908 TI - Urinary incontinence: assessment, treatment, and reimbursement. AB - Urinary incontinence is a significant problem for elderly people. Home care nurses are in a unique position to identify urinary incontinence and manage it in the home setting. Nurses can help to decrease incontinence by assessing for problems, making nursing diagnoses, and implementing appropriate treatment plans. Well-planned and documented continence care is a reimbursable nursing service for home care agencies. PMID- 8365909 TI - Supervision of home care aides. AB - The supervision of home care aides is of the utmost importance, since these aides provide needed services in the less controlled and out-of-sight private homes of patients. The role of the supervisor is demanding to assure compliance with accreditation, certification, and agency standards. Supervision of the paraprofessional staff also provides the opportunity to provide positive feedback as well as constructive criticism to assure that high-quality in-home services are provided to home-bound patients. Supervision also provides the opportunity to interact with the aides, show respect for them as individuals, and convey to them that they are an important member of the home healthcare team. PMID- 8365910 TI - Principles of universal precautions/body substance isolation. PMID- 8365911 TI - Truly universal precautions. PMID- 8365912 TI - Cultural sensitivity: educating home healthcare nurses to be transcultural nurses. PMID- 8365913 TI - Delegation and supervision of patient care. PMID- 8365914 TI - [Effect of now routine staging methods on diagnosis and therapy of head-neck neoplasms. More reliability or a new decision dilemma?]. PMID- 8365915 TI - [Improvement of communication behavior of laryngectomized and voice-rehabilitated patients by a psychological training program]. AB - An important goal of laryngectomee rehabilitation is achieving the best possible result in voice restoration. In addition to good voice quality, efficient intelligibility in daily conversation requires specific communication skills, which are very often neglected in speech therapy. In this study 51 male laryngectomees were randomized to an intervention group or an attention control group. After hospital discharge the intervention group participated in a psychological training program aimed at improving the communication behavior of the laryngectomees. This training was part of a comprehensive rehabilitation program (lasting over six months) and consisted of four modules: Improvement of communication over the disability; Discrimination of factors affecting intelligibility; Development of behavioral strategies for improving intelligibility in daily conversation; Transferring the strategies to daily live. The effectiveness of training was evaluated by a questionnaire which covered three important aspects of communication behavior. As a result of the intervention the patients influenced more effectively their own communication behavior and also influenced more adequately the behavior of typical communication partners. Present finding with the psychological training program demonstrated that the communication behavior of laryngectomees can be significantly improved. PMID- 8365916 TI - [Subablative gentamycin therapy in Meniere's disease]. AB - We have treated 20 patients suffering from unilateral Morbus Meniere (2 x 12 mg gentamicin for 7 days). These patients were controlled for 24 months. In 95% we regarded a complete or substantial control of definitive spells ("American Committee on Hearing and Equilibrium guidelines for reporting treatment results in Meniere's disease", Otolaryngol. Head and Neck Surg. 10/19-85). Only 1 patient with pretherapeutic equal caloric response showed a post-therapeutic destroyed vestibular apparatus on the treated ear. In the other 7 patients (35%), who had a loss of vestibular function after therapy, there was an already pretherapeutic more or less noticeable caloric hypoexcitability. It is possible to induce an only subablative damage with a clinical success in 95%. PMID- 8365917 TI - [Forms of monosymptomatic hereditary sensorineural hearing loss and deafness in the Leipzig area]. AB - More than one third of all sensorineural hearing loss and deafness has a genetic basis. Syndromes are already clinically distinguishable from monosymptomatic forms, but even the latter represent a heterogeneous group of diseases, which differ in mode of transmission, audiometric features of the hearing loss and possible progredience of the symptoms. Till now only audiometric and genealogical methods have been available for diagnosis. So far serological and cytogenetical studies have given no results and molecular-genetic investigations have only given results for some very rare syndromes. To help affected families and to prepare molecular-genetic studies we examined all patients at our hospital who suffer from a sensorineural hearing impairment for the onset of a monogeneous mode of transmission. Altogether we could find 39 stricken kins, 15 of them with autosomal-dominant, 16 with autosomal-recessive and 8 with an unclear mode of transmission. We registered anamnestically 1548 persons, from these 171 were suffering from hereditary hearing impairment. We were able to examine 117 of the affected persons. Seven typical audiometric features could be found. Including mode of transmission and possible progredience even 17 forms can be found. This represents a higher number of monosymptomatic forms of hereditary sensorineural hearing loss than described in the literature. It emphasizes that the main obstacle hindering future genotypical diagnosis will be the extreme high heterogenity. PMID- 8365918 TI - [Minimally invasive treatment of sialolithiasis using extracorporeal shock waves]. AB - BACKGROUND: In the past, management of sialolithiasis required surgical extirpation of the afflicted gland, in case the concrements could not be removed by dilatation or dissection of the glandular duct. The aim of the present study was to investigate the safety and efficiency of extracorporeal shockwave lithotripsy of salivary gland stones in men. PATIENTS AND METHODS: 51 patients with symptomatic solitary salivary stones which could not be removed by conservative measures received extracorporeal piezoelectric shockwave treatment. The concrements had a median diameter of 8 (4-18) mm and were located in the submandibular gland (69%) and in the parotid gland (31%). A total number of 72 shockwave treatments (maximum 3 treatments per patient) were performed under continuous sonographic monitoring. RESULTS: In 45 patients (88%) complete fragmentation of the concrements was achieved. Piezoelectric shockwave therapy was tolerated without any need for anesthesia, nor administration of sedatives or analgesics. The only untoward effects resulting from therapy were individual localized petechial hemorrhages after 10 out of 72 treatments (13%) and transient swelling of the gland immediately after shockwave application (2/72, (3%)). Twenty weeks after initial treatment 90% of the patients (46/51) were free of discomfort, and 53% of the patients (27/51) were stone free. The stone clearance rates of patients exhibiting concrements of the parotid gland (81%) were significantly higher than those of patients with stones of the submandibular gland (40%, p < 0.01). Auxiliary measures such as dilatation or dissection of the salivary duct were required only in patients suffering from concrements of the submandibular gland (20%). No long-term damage to the treated salivary gland nor to adjacent tissue structures were noted during the median follow-up period of 9 (1-24) months. CONCLUSION: Extracorporeal piezoelectric shockwave therapy promises to become a safe, comfortable and effective minimal-invasive, non surgical treatment of salivary stones. PMID- 8365919 TI - [Ectopic teeth in the area of the paranasal sinuses]. AB - In contrast to dentogenious affections of the sinus maxillaris ectopic or supernumerary teeth in the paranasal sinuses are seldom. Ectopic teeth located at the ostium of the sinus maxillaris are rare, intranasal teeth are very rare and ectopic/supernumerary teeth in the sinus etmoidalis are a curiosity. We report about two patients with such ectopic teeth. A 55 year old woman had a rootless tooth in her right sinus ethmoidalis which had caused a "pseudopolyposis" with consecutive nasal airway obstruction and severe headache. A 59 year old man had ectopic teeth in both sinus maxillaris which obstructed the left ostium, causing dumbness of the left cheek and severe headache. Both patients have been cured by operation. However the presented patients demonstrate that even elaborated radiological efforts could not prove diagnosis. The etiology, diagnostical steps and treatment of these teeth are discussed. The surrounding soft tissue should be examined histologically after resection of such a tooth to prevent the development of a residual cyst and to notice the extremely rare development of malignancies deriving from the highly potential tissue of the dental follicle. PMID- 8365920 TI - [Differential diagnosis of dysphagia]. AB - The symptom dysphagia is defined and an interdisciplinary team approach emphasized. A step like diagnostic approach in oropharyngeal dysphagia is described, including transnasal pharyngo-laryngo-fiber endoscopy, videofluoroscopy and the "modified barium swallow." First, all of the organic changes causing oropharyngeal dysphagia must be recognized, both "typical ENT diseases" and malignant tumors of the oropharynx and hypopharynx, which are usually diagnosed only at an advanced stage. Of particular interest is postoperative dysphagia with or without aspiration. If there is no evidence of an organic cause in the field of otorhinolaryngology, in making a differential diagnosis dysfunction of the upper esophageal sphincter and a "globus pharyngis" have to be ruled out. PMID- 8365921 TI - The American Society for Histocompatibility and Immunogenetics, 19th Annual Meeting. Phoenix, Arizona, October 2-7, 1993. Abstracts. PMID- 8365922 TI - Research advances in the fight against the acquired immunodeficiency syndrome (AIDS) PMID- 8365923 TI - Physicians' role in controlling diabetes requires 'detective' work. PMID- 8365924 TI - Fasting hyperglycemia in type I diabetes mellitus. AB - The differential diagnosis of fasting hyperglycemia in type I diabetes includes the Somogyi effect, the dawn phenomenon, and insufficient insulin administration. To determine the causes of fasting hyperglycemia and their effect on subsequent daytime blood glucose control, the authors retrospectively reviewed blood glucose profiles of 126 patients with type I diabetes. The Somogyi effect accounted for 12.6% of all instances of fasting hyperglycemia, the dawn phenomenon, 24.1%, and poor control, 63.3%. Measurement of 3 AM and 5 AM blood glucose values is the key to making a correct diagnosis. Once a patient's fasting hyperglycemia is placed in one of these groups, appropriate treatment can be started. PMID- 8365925 TI - Anomalous inferior vena cava with azygos continuation. AB - Five patients who underwent cardiac catheterization at three separate institutions during a period of 6 years were found to have anomalous inferior vena cava with azygos continuation. Although it is not uncommon to detect this defect in pediatric patients with congenital heart disease, it may be an unusual finding for an angiographer who works primarily with adults. This article serves as a reminder of the existence of this potentially confusing anomaly, usually associated with other congenital cardiac abnormalities. PMID- 8365927 TI - Support groups address residents' personal development. AB - Graduate medical education traditionally has emphasized the teaching of biomedical knowledge and technical skills. However, physicians-in-training also need opportunities to explore their emotional reactions that occur during the process of patient care and medical training. The promotion of personal growth and self-awareness should be important components of graduate medical education. Easily implemented, a resident support group is one forum that addresses this obvious gap in medical education. This article reviews the goals and structure of support groups, with the hope that more training programs will implement them. PMID- 8365926 TI - Tennis elbow: a biomechanical and therapeutic approach. AB - Lateral epicondylitis, one of the most common lesions of the arm, affects some 50% of tennis players. This condition poses a problem in clinical management because treatment is dependent not only on proper medical therapy but also on correction of the improper on-court biomechanics. The most common flaw is a late contact on the backhand groundstroke, forcing the player to extend the wrist with the extensor muscles. This action predisposes to trauma of the tendon fibers at the lateral epicondyle. Understanding the biomechanics will better prepare the physician to advise the patient and to communicate with a tennis teaching professional to facilitate long-term relief. PMID- 8365928 TI - Acute mastocytosis: a potential dermatologic emergency. AB - A comatose patient arrived at the emergency room with apnea and in shock after a grand mal seizure. A maculopapular rash, not initially observed, led to a diagnosis of cutaneous mastocytosis. Degranulation of the mast cells with massive histamine release had resulted in cardiovascular collapse. The authors follow a detailed report of this case history with a discussion of the diagnosis and treatment of the acute systemic stage of this potentially life-threatening illness. PMID- 8365929 TI - Possible association of interleukin-2 treatment with depression and suicide. AB - Immunomodulatory agents for the treatment of certain oncologic disorders are rapidly moving from the research laboratory into clinical practice. These agents may not be void of potential neuropsychiatric sequelae. The following clinical report concerns a previously nondepressed patient with no history of psychiatric disorders who became depressed and killed himself while being treated with interleukin-2. It is important that consulting psychiatrists be sensitive to acute emotional changes in cancer patients taking immunomodulatory agents. PMID- 8365930 TI - Phantom evaluation of heating of superficial tissues located above interstitial microwave antennas. AB - PURPOSE: A technique that improves heating of superficial tissues above an implant of microwave interstitial antennas is presented. METHODS AND MATERIALS: Adequate heating of tumor margins is achieved by extending an implant of microwave antennas beyond the tumor boundary by 1-2 cm. When the tumor infiltrates the superficial tissues including the skin, the implant cannot even reach the superficial margin of the tumor since it requires tissue to support the catheters. This may yield cold spots in the tissues above the implant. Measurements in a phantom with varying thickness of the superficial layer above the implant demonstrated inadequate Specific Absorption Rates of energy distribution in this layer. A method that improves these distributions in the superficial layers was developed and tested in this work. This method requires placing a deionized water bolus on the phantom (patient) surface. Additional microwave antennas are placed on top of the bolus above and parallel to the implanted antennas. The Specific Absorption Rates distributions were evaluated for the thicknesses of superficial layer ranging from 1.5 mm to 16 mm and two bolus thicknesses (5 and 10 mm). RESULTS: The adequate Specific Absorption Rates distributions were achieved for all tested thicknesses of the superficial layer (1.5, 4, 8, 12, and 16 mm). The use of the 5 mm bolus versus 10 mm bolus is discussed. The use of additional antennas did not significantly increase stray radiation. CONCLUSION: This method has the potential to optimize heating of superficial tissues located above a microwave antenna implant. PMID- 8365931 TI - Results of a policy of surveillance in stage I testicular seminoma. AB - PURPOSE: To determine what proportion of patients with Stage I testicular seminoma will be cured with orchidectomy alone. METHODS AND MATERIALS: From August 1984 to December 1991 148 patients with Stage I testicular seminoma were entered on a prospective study of surveillance following orchidectomy. The eligibility criteria included a normal chest X ray, lymphogram, computed tomography (CT) of the abdomen and pelvis, and normal post-orchidectomy tumor markers (AFP and BHCG). Patients were followed with a clinical assessment (markers, chest X ray and CT abdomen and pelvis) at 4 to 6 monthly intervals. RESULTS: With a median follow-up of 47 months (range 7-87 months), the actuarial relapse-free rate was 81% at 5 years. Twenty-three patients have relapsed with a median time to relapse of 15 months (range 2-61 months). Four patients (17%) relapsed at 4 or more years from diagnosis. Twenty-one of the 23 relapses occurred in the paraaortic lymph nodes, one patient relapsed in the mediastinum and ipsilateral inguinal nodes and one patient had an isolated ipsilateral inguinal node relapse. Nineteen patients were treated for relapse with external beam radiation therapy of which three developed a second relapse and were salvaged with chemotherapy. Four patients were treated for first relapse with chemotherapy and one developed a second relapse and died of disease. Age at diagnosis was the only prognostic factor for relapse, with patients age < or = 34 having an actuarial relapse-free rate at 5 years of 70% in contrast to a 91% relapse-free rate in those > 34 years of age. CONCLUSIONS: We recommend that surveillance in Stage I testicular seminoma should only be performed in a study setting until further data regarding the risk of late relapse and the efficacy of salvage chemotherapy is available. PMID- 8365932 TI - Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: results of the RTOG dose escalating protocol. AB - PURPOSE: This study was prepared to address two objectives: (a) to determine whether progressively higher total doses of hepatic irradiation can prolong survival in a selected population of patients with liver metastases; (b) to refine existing concepts of liver tolerance for fractionated external radiation employing a fraction size which might be appropriate in clinical protocols evaluating elective or adjuvant radiation of the liver. METHODS AND MATERIALS: One hundred seventy-three analyzable patients with computed tomography measurable liver metastases from primary cancers of the gastrointestinal tract were entered on a dose escalating protocol of twice daily hepatic irradiation employing fractions of 1.5 Gy separated by 4 hr or longer. Sequential groups of patients received 27 Gy, 30 Gy, and 33 Gy to the entire liver and were monitored for acute and late toxicities, survival, and cause of death. Dose escalation was implemented following survival of 10 patients at each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis. RESULTS: The use of progressively larger total doses of radiation did not prolong median survival or decrease the frequency with which liver metastases were the cause of death. None of 122 patients entered at the 27 Gy and 30 Gy dose levels revealed clinical or biochemical evidence of radiation induced liver injury. Five of 51 patients entered at the 33 Gy level revealed clinical or biochemical evidence of late liver injury with an actuarial risk of severe (Grade 3) radiation hepatitis of 10.0% (+/- 7.3% S.E.) at 6 months, resulting in closure of the study to patient entry. CONCLUSION: The study design could not credibly establish a safe dose for hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of delayed radiation injury. The absence of apparent late liver injury at the 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer may have employed an insufficient radiation dose (21 Gy) to fully test the question. PMID- 8365933 TI - A nomograph for permanent implants of palladium-103 seeds. AB - 103Pd is being substituted for 125I in permanent implants for which it is desired to deliver a higher initial dose rate while maintaining readily achieved radiation protection. We have constructed a nomograph to assist in determining both the total seed strength required and the appropriate needle spacing for 103Pd implants. We have calculated the "matched peripheral dose" (MPD), that is, the dose for which the isodose contour volume is equal to the target volume, for 64 125I and 13 103Pd actual implants as if 103Pd had been used for all of them, employing a computer lookup table based on single-seed dose distribution measurements in solid water. The calculated data were used to obtain a least squares fit to a linear relationship between the logarithm of the total seed strength for a given MPD and the logarithm of the average dimension, da (cm). We found that, for a nominal MPD of 11,500 cGy, total seed strength (in mCi) is given by 3.2 da2.56. A 103Pd nomograph has been constructed on the basis of this power function relationship. Our nomographic guide for planning 103Pd implants calls for total seed strength to increase significantly faster as a function of target volume average dimension than is the case for 125I. This nomograph will facilitate the application of 103Pd seeds in permanent implants. PMID- 8365934 TI - Online repositioning during treatment of the prostate: a study of potential limits and gains. AB - PURPOSE: With on-line portal imaging devices and image registration tools, the verification of radiation field position prior to each treatment becomes technically feasible. In this paper, we analyze the impact of pre-treatment verification and field position adjustment on target coverage and normal tissue sparing. METHODS AND MATERIALS: Port films were compared with corresponding simulation films to determine the magnitude of setup variations in patients treated for prostate cancer. From these data, an analytic function was determined between geometric coverage of the target and field margin size. A paradigm for on line patient repositioning was employed to generate a new relationship between margin and target coverage. Margins were selected for the situations of normal treatment and on-line repositioning to ensure target coverage. Dose-volume histograms were generated for a typical prostate treatment using these margins. RESULTS: On-line repositioning, when setup errors exceed 1 cm, results in a 6 mm reduction in margin, suggesting that 10% of the volume of bladder and rectum may be spared of high dose. CONCLUSION: The use of on-line imaging and image registration to guide adjustment of patient setup may lead to a reduction in the volume of normal tissues irradiated, and possibly improve the probability of complication-free survival in future treatments. PMID- 8365935 TI - Digitally reconstructed fluoroscopy and other interactive volume visualizations in 3-D treatment planning. AB - PURPOSE: Add radiographic context to the beam's-eye-view used in 3-dimensional treatment planning. Improve methods for interactive visualization of anatomy and dose distributions. METHODS AND MATERIALS: Most 3-dimensional treatment planning systems feature a beam's-eye view that includes only graphical representations of patient anatomy. With input devices such as a mouse or trackball, the user interactively shapes the treatment field using the graphical models to provide geometric information. Radiographic context provides additional geometric information important for determining field shape. We have implemented digitally reconstructed fluoroscopy in the beam's-eye view by increasing the efficiency for computing digitally reconstructed radiographs. In addition we have improved algorithms for real-time surface and volume rendering for anatomy and doses using an experimental graphics supercomputer. RESULTS: Without radiographic context in the beam's-eye-view, field shapes were sometimes changed after simulation or portal images were obtained. Digitally reconstructed fluoroscopy has essentially eliminated these changes. Higher quality interactive three-dimensional displays improve the comprehension, confidence and efficiency of the user. Our improvements have already been implemented on one model of a new generation of commercial graphics workstations. CONCLUSION: Addition of radiographic context to the beam's-eye-view is recommended. Incorporation of higher quality interactive graphics is rapidly becoming practical and is encouraged. PMID- 8365936 TI - Dosimetric evaluation of total scalp irradiation using a lateral electron-photon technique. AB - PURPOSE: To evaluate the radiation dosimetry of a new technique for total scalp irradiation. METHODS AND MATERIALS: A treatment technique described by Akazawa (1989) has been studied. During each fraction, two electron and two photon fields are treated. While most of the lateral scalp is treated with the electron fields, a rind of scalp close to the midsagittal plane is irradiated by parallel-opposed lateral photon fields. A wax bolus is used to build up skin dose and to protect the brain from electron dose. The dose distribution and dose-volume histograms were evaluated for different field arrangements using a 3-dimensional treatment planning system. After modifying the technique, in-vivo thermoluminescent dosimetry were used to evaluate the dose distributions for the first two patients. RESULTS: To compensate for the lack of dose from the opposed photon field at the junction, the technique was modified using overlapped fields instead of abutting fields. A field overlap of 3 to 4 mm between the electron and photon fields was found optimal. When used with the field junction shift of 1 cm midway through the treatment, this scheme resulted in a dose uniformity of -5% to +15% of the prescribed dose in the region of abutment. Results of the 3-dimensional dose calculation were supported by in-vivo thermoluminescent dosimetry on two patients. CONCLUSION: On the basis of computer dose calculations and in-vivo dosimetry. Akazawa's technique for scalp irradiation can be improved by using a 3 to 4 mm overlap of electron and photon fields. This modified technique is practical and produces clinically acceptable dosimetry. PMID- 8365937 TI - The combination of cis-platin based chemotherapy and radiation in the treatment of muscle-invading transitional cell cancer of the bladder. AB - Radical cystectomy is the standard of care for patients with muscle-invading transitional cell carcinoma of the bladder. More limited surgery is only useful in highly selected patients and radiation therapy alone gives overall local control rates under 40%. Phase II studies have shown that when radiation and trans-urethral surgery are combined with cis-platin based chemotherapy local control rates increase such that the majority of patients preserve a tumor-free functional bladder. Up to 85% of patients selected for bladder sparing therapy on the basis of their initial response to chemo-radiation may keep their bladders. This figure could increase further when other powerful prognostic factors such as the presence of hydronephrosis, the presence of carcinoma in situ, and DNA ploidy are also taken into account in initial patient selection. The activity of cisplatin combinations in metastatic disease is not in doubt with up to 50% response rates generally reported. The hope that this will translate into the eradication of micrometastatic disease (known to be present in up to 40% of patients at diagnosis) has yet to be borne out. Those randomized trials so far reported have not shown any survival advantage when combined-modality therapy is compared to radiation alone. The addition of combination chemotherapy to radiation does not increase bladder morbidity but carries a considerable systemic penalty. Thus, despite promising Phase II studies, until local control and survival benefit is proven in a randomized trial it should continue to be regarded as experimental. PMID- 8365938 TI - Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy. AB - PURPOSE: To clarify the controversy about the management and prognosis of human chorionic gonadotropin-producing seminoma, the records of 132 patients with abnormal human chorionic gonadotropin values treated with radiotherapy were analyzed. METHODS AND MATERIALS: The records of 1169 patients with pure seminoma treated in 10 institutions were screened for serum or urinary human chorionic gonadotropin. One hundred and thirty two patients with elevated human chorionic gonadotropin were found: 96 Stage I, 20 IIA, 7 IIB, 8 III and 1 IV. Median age was 34 y., mean follow-up was 5.0 years [range 1-12 y]. All received infradiaphragmatic radiotherapy (median dose 30 Gy), 25 (2 Stage I, 11 IIA, 5 IIB and 7 III) supradiaphragmatic radiotherapy (median dose: 28.5 Gy) and 10 had also initial chemotherapy (3 Stage IIB 6 III and 1 IV). Patients were allocated to three groups according to human chorionic gonadotropin values: (a) moderate elevation: up to 10 times (104 pts), (b) high elevation: 10 to 100 times (20 pts), (c) very high elevation: over 100 times the upper limit of normal value (8 pts). RESULTS: The proportion of Stage I, II and III was 76%, 19%, 5% in the ME group versus 50%, 35%, 15% in the high elevation group (p < 0.05). In the very high elevation group there were 7 Stage I and 1 Stage IV. Of 132 patients, six died (three dead of disease, two suicides, one acquired immunodeficiency syndrome). The 5 years overall survival probability was 94%. There were seven recurrences (initial stage: 1 Stage I, 2 IIB, 3 III and 1 IV). Of these, there were one in-field recurrence, 3 out of field and 3 in both sites. In 5 of 7, the human chorionic gonadotrophin level was again elevated at recurrence. The 5 years recurrence-free-survival probability was 94% (98% for Stage I, 100% for Stage IIA and 65% for Stage IIB and III [p < 0.001 between I and IIB + III, p < 0.05 between IIA and IIB + III]). Four of the 7 recurrences were salvaged by chimiotherapy +/- radiotherapy. In the high elevation and very high elevation groups, the 5 years recurrence-free-survival was 88%, vs. 96% for the moderate elevation group (p = 0.10). CONCLUSION: Based on this series of patients, human chorionic gonadotropin production is not an unfavorable prognostic factor in pure seminoma. Even in the subgroups with high or very high human chorionic gonadotropin levels (who had a higher proportion of advanced stages), the prognosis remained excellent. In Stage I and IIA seminoma with abnormal human chorionic gonadotropin levels, recurrence rate after post-operative radiotherapy alone is extremely low. PMID- 8365939 TI - Anal cancer--radiation alone or with cytotoxic drugs? PMID- 8365940 TI - In reference to Jack F. Fowler's alpha, beta, alpha/beta and s. PMID- 8365941 TI - Predictive value of perfusion lung scans on post irradiation pulmonary function. PMID- 8365942 TI - Renal tolerance to nonhomogenous irradiation: comparison of observed effects to predictions of normal tissue complication probability from different biophysical models. AB - PURPOSE: A patient series was analyzed retrospectively as an example of whole organ kidney irradiation with an inhomogenous dose distribution to test the validity of biophysical models predicting normal tissue tolerance to radiotherapy. METHODS AND MATERIAL: From 1969 to 1984, 142 patients with seminoma were irradiated to the paraaortic region using predominantly rotational techniques which led to variable but partly substantial exposure of the kidneys. Median follow up was 8.2 (2.1-21) years and actuarial 10-year survival (Kaplan Meier estimate) 82.8%. For all patients 3-dimensional dose distributions were reconstructed and normal tissue complication probabilities for the kidneys were generated from the individual dose volume histograms. To this respect different published biophysical algorithms had been introduced in a 3-dimensional-treatment planning system. RESULTS: In seven patients clinical manifest renal impairment was observed (interval 10-84 months). An excellent agreement between predicted and observed effects was seen for two volume-oriented models, whereas complications were overestimated by an algorithm based on critical element assumptions. CONCLUSIONS: Should these observations be confirmed and extended to different types of organs corresponding algorithms could easily be integrated into 3-dimensional-treatment planning programs and be used for comparing and judging different plans on a more biologically oriented basis. PMID- 8365943 TI - Treatment of stage I testis seminoma by radiotherapy: long-term results--a 30 year experience. AB - PURPOSE: From 1956 to 1986, we have retrospectively studied 184 patients with a Stage I testis seminoma treated by orchidectomy and radiotherapy at the Institut Gustave Roussy. METHODS AND MATERIALS: The 184 patients received adjuvant radiotherapy to the para-aortic and ipsilateral iliac nodes. Of the 184 patients, 133 received additional mediastinal and supraclavicular irradiation, 47 received supraclavicular without mediastinum irradiation, 98 patients received additional radiotherapy given to inguino-scrotal area. The mean dose of irradiation is 21 Gy which is the lowest dose published. The actuarial survival rate is, respectively, 96%, 93%, 83% and 77% at 5, 10, 15, and 20 years. RESULTS: Four patients relapsed, and four died of progressive disease. Four patients presented cardiovascular disease, all of them had mediastinal irradiation, two were heavy smokers. Seventeen second malignancies were observed, six tumors in the contralateral testis. The actuarial risk of developing a second malignancy is 10% at 10 years, 21% at 20 years. The cure rate and relapse rate in our patients is the same as that obtained by higher dosage of irradiation. CONCLUSION: We conclude that low dose of prophylactic irradiation in lumbo aortic and ipsilateral iliac lymph nodes is active and safe in the treatment of Stage I testis seminoma. PMID- 8365944 TI - Chemoradiotherapy versus radiotherapy alone for anal cancer: a retrospective comparison. AB - PURPOSE: To evaluate the effect of adding one cycle of concomitant chemotherapy to curative radiotherapy on tumor control and toxicity in the treatment of anal cancer. METHODS AND MATERIALS: One hundred twenty-five patients completed curative sphincter-conserving treatment, 57 with radiotherapy alone and 68 with concomitant chemo-radiotherapy. Compared with chemoradiotherapy patients, radiotherapy patients were older (median age 71 vs 63) and had less advanced tumors (T3-4 26% vs 51%). Radiotherapy patients were usually treated with a direct perineal cobalt field (mean dose 31 Gy at 5 cm/10 fractions/3 weeks), complemented in most cases by a sacral are field, followed (mean split 54 days) by Iridium-192 implantation (mean dose 23 Gy, Paris system). The large majority of chemoradiotherapy patients received antero-posterior opposed 10 MV photon fields, including pelvic and inguinal nodes (mean dose 38 Gy/19 fractions/4 weeks), followed (mean split 42 days) by implant boost (mean dose 18 Gy). In addition, chemo-radiotherapy patients received starting on day 1 an IV bolus of Mitomycin-C, 0.4 mg/kg (maximum 20 mg) and a 5-day continuous infusion of 5 fluorouracil 600-800 mg/m2/day. Median follow-up was 65 months for radiotherapy and 48 months for chemo-radiotherapy patients. RESULTS: For all 125 patients at 5 years, overall survival was 65.5%, definitive local control 83% and local control with sphincter preservation 68%. Overall and stage for stage, there was no difference in overall, progression-free or cancer-specific survival, nor in local control, local-regional control, or sphincter preservation rates between patients treated with chemoradiotherapy vs. radiotherapy alone. There was no significant difference between the two groups regarding acute or late toxicity. CONCLUSION: This retrospective analysis does not confirm the efficacy of one course of simultaneous Mitomycin-C and 5-fluorouracil, at least in association with full dose radiotherapy incorporating Iridium-192 boost. PMID- 8365945 TI - Definitive postoperative irradiation of bile duct carcinoma with charged particles and/or photons. AB - PURPOSE: To determine the rates of survival and local control in patients with bile duct adenocarcinomas treated with post-operative photons and/or charged particles. METHODS AND MATERIALS: A retrospective study was performed analyzing all patients with bile duct adenocarcinomas who received radiotherapy through the University of California San Francisco and at Lawrence Berkeley Laboratory between 1977 and 1987, a total of 62 patients. University of California San Francisco patients received photon therapy (median dose 5400 cGy), and Lawrence Berkeley Laboratory patients were treated with the charged particles helium and/or neon (median dose 6000 cGyE). Forty-eight patients were treated post operatively with curative intent, 30 with photons and 18 with particles. Thirty six patients in the study had gross residual disease; none had microscopically negative margins. RESULTS: The overall two-year actuarial survival was 28%: 44% for particle-treated patients and 18% for patients treated with photons (p = .048). Median actuarial survival was 23 months in particle patients and 12 months in photon patients. Local control was also improved, though less significantly, in patients treated with particles (median disease-free survival 20 months vs. 4.5 months, p = .054). A univariate and multivariate analysis was performed and revealed that only extent of residual disease predicted local failure and overall survival; no other prognostic factors were identified. CONCLUSION: Compared to conventional photon radiotherapy, treatment with post-operative charged particle irradiation at Lawrence Berkeley Laboratory appeared to offer a survival advantage in this non-randomized series. Additional investigation into protection of surrounding normal tissue with better dose localization through the use of charged particles is planned. PMID- 8365946 TI - In vitro characterization of radiotherapy-induced morphonuclear modifications on chemosensitive as opposed to chemoresistant neoplastic cells. AB - PURPOSE: We describe by means of digital cell image analysis the influence of X ray radiation on three in vitro cultured cell lines for which we set up chemosensitive and chemoresistant variants. METHODS AND MATERIALS: The three cell lines correspond to the MXT mouse mammary and the T24 and J82 neoplastic human bladder cells. The digital cell image analysis was carried out by computing morphometric (nuclear size), densitometric (proportion of cells in the G2 cell cycle phase), and textural features (chromatin pattern characteristics) on Feulgen-stained nuclei. RESULTS: The results show that such digital cell image analyses make it possible to monitor radiotherapy-induced effects on these morphonuclear characteristics accurately. X-ray radiotherapy induces a dose dependent increase in the proportion of cells in the G2 phase of the cell cycle along with a decrease in the overall chromatin condensation level. These two concomitant phenomena lead to a marked radiotherapy-induced increase in nuclear size. We also observed that radiotherapy-induced effects at the morphonuclear level are not only highly specific to the cell type analyzed, that is MXT mouse mammary or J82 or T24 human bladder carcinoma cells, but also to the fact that the cells are either chemosensitive or chemoresistant. CONCLUSION: The digital cell image analyses of Feulgen-stained nuclei is helpful in monitoring the irradiation-induced morphonuclear modifications. PMID- 8365947 TI - Treatment of radiation nephropathy with ACE inhibitors. AB - PURPOSE: A previous study showed that radiation nephritis could be treated with captopril, an angiotensin-converting-enzyme inhibitor. These studies were designed to determine whether other angiotensin-converting-enzyme inhibitors would be effective, whether captopril would inhibit the development of the histopathologic lesions typical of radiation nephritis, and whether captopril could be used to treat the nephropathy observed in bone marrow transplant recipients conditioned with total body irradiation. METHODS AND MATERIALS: In radiation nephritis studies, rats were given 17-27 Gy bilateral renal irradiation in 5 fractions. Six months after irradiation animals were stratified by blood urea nitrogen and assigned to no treatment, or treatment with captopril (500 mg/l) or enalapril (50 mg/l) in the drinking water. A subset of animals was sacrificed for histopathology after 3 months; the remaining animals continued on drugs for 7 months. In the bone marrow transplant nephropathy study, rats received 14-17 Gy total body irradiation in 6 fractions over 3 days followed by syngeneic bone marrow transplant. Six months after irradiation, animals were stratified by blood urea nitrogen and assigned to no treatment, or treatment with captopril (500 mg/l). Animals remained on drugs for 6 months. In all studies animals were followed with periodic renal function tests. RESULTS: In the radiation nephritis study, survival and renal function were significantly enhanced by both captopril and enalapril, but there were no significant differences between the drugs. The histopathologic severity of the lesions of radiation nephritis correlated with the degree of renal dysfunction; and in irradiated animals with equal initial azotemia, captopril-treated rats developed less severe renal lesions. Finally, captopril also prolonged survival and preserved renal function in this rat bone marrow transplant nephropathy model. CONCLUSION: Angiotensin-converting-enzyme inhibitors are an effective treatment for both radiation nephritis and bone marrow transplant nephropathy. PMID- 8365948 TI - The orthodox Jungian perspective on gender differences in consciousness. A re examination. PMID- 8365949 TI - Multiple personality and the complex theory. A correction and a rejection of C. G. Jung's 'collective unconscious'. PMID- 8365950 TI - Inhibition of enterobacteria and Listeria growth by lactic, acetic and formic acids. AB - Minimum inhibitory concentrations (MIC) of undissociated lactic, acetic and formic acids were evaluated for 23 strains of enterobacteria and two of Listeria monocytogenes. The evaluation was performed aerobically and anaerobically in a liquid test system at pH intervals of between 4.2 and 5.4. Growth of the enterobacteria was inhibited at 2-11 mmol l-1, 0.5-14 mmol l-1 and 0.1-1.5 mmol l 1 of undissociated lactic, acetic and formic acids, respectively. The MIC value was slightly lower with anaerobic conditions compared with aerobic conditions. The influence of protons on the inhibition was observed for acetic acid at the low pH values. Undissociated lactic acid was 2 to 5 times more efficient in inhibiting L. monocytogenes than enterobacteria. Acetic acid had a similar inhibitory action on L. monocytogenes compared with enterobacteria. Inorganic acid (HCl) inhibited most enterobacteria at pH 4.0; some strains, however, were able to initiate growth to pH 3.8. The results indicate that the values of undissociated acid which occur in a silage of pH 4.1-4.5 are about 10-100 times higher than required in order to protect the forage from the growth of enterobacteria and L. monocytogenes. PMID- 8365951 TI - Classification of the spoilage flora of raw and pasteurized bovine milk, with special reference to Pseudomonas and Bacillus. AB - Eighty-one bacterial strains isolated from refrigerated raw milk, 124 from pasteurized milk and cream stored at 5 degrees C and 7 degrees C, and 19 type and reference strains of Pseudomonas spp. and Bacillus spp. were characterized by numerical phenotypic analysis. Data were processed with simple matching (SSM) and Jaccard (SJ) coefficients, and UPGMA clustering. Fourteen clusters of Gram negative bacteria were formed at SJ = 79% (SSM = 90%). Raw milk was exclusively spoilt by Gram-negative bacteria, the majority of which were Pseudomonas fluorescens biovar I, Ps. fragi, Ps. lundensis and Ps. fluorescens biovar III. Minor groups in raw milk included Enterobacteriaceae spp. and Acinetobacter spp. Pasteurized milk was spoilt by essentially the same Gram-negative organisms in 65% (5 degrees C) and 50% (7 degrees C) of the cases. The phenotypic characteristics of Gram-negative bacteria are given. Bacillus polymyxa (both temperatures) and B. cereus (only at 7 degrees C) were responsible for 77% of samples spoiled by the Gram-positive organisms. Minor milk spoilage groups included other Bacillus spp. and lactic acid bacteria. All Bacillus spp. grew fermentatively in milk, and most strains denitrified. It is suggested that: (i) industrial recontamination tests of pasteurized milk are directed against Pseudomonas; (ii) milk is stored at 5 degrees C or lower to avoid growth of B. cereus; and (iii) the significance of gas-producing and nitrate/nitrite-reducing Bacillus strains is recognized in cheese production. PMID- 8365952 TI - Some factors affecting airborne survival of Pseudomonas fluorescens indoors. AB - The effect of relative humidity (RH) on the airborne survival of a Pseudomonas fluorescens strain was studied at 20, 40, 60 and 80% RH indoors. The aero-stable spore of Bacillus subtilis subsp. niger, used as a tracer of physical losses was compared with a light scattering particle counter, as there were doubts about the reliability of the spore as tracer. The Rion counter was validated before use and found to give a good estimate of relative physical losses providing spray suspensions contained between 10(7) and 10(9) cfu ml-1 cells and that the humidity was not more than 80% RH. Pseudomonas fluorescens, strain P+S+, suspended in distilled water survived best at mid humidities and least at 80% RH. When suspended in 1% glycerol there was an apparent 'increase' in viability after an initial rapid reduction. This was thought to be due to delay in equilibration of glycerol in the cell membrane after concentration on dehydration. The cells were thought to be unstable and sensitive to the stress of rehydration before equilibration occurred. The findings are discussed in relation to Cox's theories of outer membrane damage on aerosolization. PMID- 8365953 TI - Interrelationships between strains of Salmonella enteritidis belonging to phage types 4, 7, 7a, 8, 13, 13a, 23, 24 and 30. AB - Salmonella enteritidis strain P278849 expressed long-chain lipopolysaccharide (LPS, termed 'smooth'), carried plasmids of 38, 34 (pDEP 44, incompatibility group N, R-type AS), 2.0 and 1 MDa, and belonged to phage type (PT) 23. Introduction of pDEP 44 into a smooth strain of Salm. enteritidis PT 4 produced a smooth strain of Salm. enteritidis of PT 24. Transfer of this plasmid into a strain of PT 8 also resulted in formation of a smooth strain of Salm. enteritidis of PT 24. Moving pDEP 44 into strains of Salm. enteritidis of PTs 7 or 7a which did not express LPS (termed 'rough') resulted in rough strains of PT 23. In contrast, transfer of this plasmid into a smooth strain of Salm. enteritidis PT 7a resulted in a smooth strain of PT 23. Introduction of pDEP 44 into strains of Salm. enteritidis of PT 13 or PT 13a did not change the phage type, whereas transferring the plasmid into strains of PT 30 caused strains to become resistant to lysis by the typing phages and therefore untypable. The possibility of strains of Salm. enteritidis of PT 8 being the progenitors of strains of Salm. enteritidis of PT 24 must now be considered when investigating the epidemiology of Salm. enteritidis of PT 24 infections in areas where Salm. enteritidis PT 8 is common. PMID- 8365955 TI - In vitro susceptibility of Clostridium perfringens isolated from farm animals to growth-enhancing antibiotics. AB - Minimal inhibitory concentration (MIC) determinations were carried out with seven growth-enhancing antibiotics against 95 Clostridium perfringens field isolates obtained during 1991 and 1992 from poultry, pigs and calves. All were resistant to 64 micrograms ml-1 of the bambermycin antibiotic, flavomycin (flavophospholipol) and susceptible to avoparcin (MIC90 0.25 micrograms ml-1), avilamycin (MIC90 0.5 micrograms ml-1) and salinomycin (MIC90 < or = 0.12 micrograms ml-1). Acquired resistance against bacitracin was detected in some isolates from poultry and bovines and resistance to tylosin and virginiamycin in some strains from all species investigated. Overall, the prevalence of resistance was comparable to the low levels recorded in 1979 in Cl. perfringens isolates from the same animal host species. PMID- 8365954 TI - Occurrence of campylobacters in small domestic and laboratory animals. AB - Faeces samples from 156 healthy domestic pets and laboratory animals were examined for campylobacters with both a selective medium (Campylobacter Blood Free Medium; Oxoid, CM739) and selective filtration through a 0.65 micron pore size filter. Campylobacter spp. were isolated from 78 of the samples; filtration was the most effective method. Isolates were characterized by biochemical tests and DNA/DNA hybridization with whole chromosomal DNA from reference strains as probes. Campylobacter upsaliensis was the most common species isolated from cats (45 from 68 samples) whilst Camp. jejuni was more often isolated from dogs (19 from 56 samples). More attention should be paid to pets as a potential source of campylobacters capable of causing diarrhoea in human beings. Procedures other than those involving currently-used selective agents must be employed to efficiently detect all campylobacters. PMID- 8365956 TI - Development of a 24 h screen to detect viable salmonellas in faeces. AB - A 24 h screen to detect viable salmonellas in faeces was developed by studying growth dynamics of salmonellas and competing flora in combinations of enrichment media and artificially-inoculated pig faeces. Muller-Kauffmann tetrathionate (MK) broth, incubated overnight at 42 degrees C, maintained the lowest ratio of salmonella: competing flora and identified all inoculated samples. A 4 h postenrichment in M broth plus novobiocin reduced the number of false-positive results in subsequent ELISAs. Adjusting the negative cut-off values and incubation time of the chromogenic substrate from that recommended in the ELISA instructions reduced the rate of false-positive results further and allowed the detection of 10(3) salmonellas per ml in the presence of up to 10(7) ml-1 aerobic competing cells. Suspension of faeces diluted 1 in 2 and 1 in 5, rather than 1 in 10 in MK broth did not necessitate further adjustments to the ELISA baseline values. The proposed screen protocol is an overnight incubation of faeces suspended 1 in 10 in MK broth, a 1 in 100 subculture into M broth plus 10 micrograms ml-1 novobiocin (MbN) for 4 h, steam inactivation of MbN cultures and testing by ELISA, and can detect three salmonella cells per g faeces. PMID- 8365957 TI - Comparison of classical isolation protocols with a 24 h screen to detect viable salmonellas in faeces. AB - A 24 h screen which detects three viable salmonella cells per g of faeces was compared with classical isolation procedures for their ability to identify salmonella-positive samples from a pig rearing unit. The screen involved an overnight enrichment in Muller-Kauffmann tetrathionate (MK) broth, subculture for 4 h in M broth containing 10 micrograms ml-1 novobiocin, followed by detection of the presence of salmonellas by BacTrace and Salmonella-tek ELISAs. The classical protocols were: (1) an overnight and 48 h incubation in MK or selenite cysteine broth; or (2) overnight incubation in buffered peptone water and 24 h subculture in Rappaport-Vassiliadis broth (BPW-RV). Salmonellas were isolated from the broth cultures on xylose lysine deoxycholate and brilliant green agars. Thirty four of 100 samples were positive for salmonellas but no single isolation protocol identified all of them. The best of the classical isolation protocols, 48 h incubation in MK broth, identified 27 (79%) of the 34 positive samples whilst the screen identified 26 (76%) of the 34 positive samples. False-positive results were obtained from all isolation protocols except BPW-RV. PMID- 8365958 TI - A new method for the concentration of Cryptosporidium oocysts from water. AB - A novel method for the concentration of Cryptosporidium oocysts from water has been developed, based upon the precipitation of calcium carbonate. A 10 l water sample is treated by adding solutions of calcium chloride and sodium bicarbonate and raising the pH value to 10 with sodium hydroxide. Crystals of calcium carbonate form and enmesh particles in the Cryptosporidium oocyst size range. The crystals are allowed to settle, the supernatant fluid is discarded and the calcium carbonate precipitate dissolved in sulphamic acid. The sample can be concentrated further by centrifugation. Recoveries of oocysts from seeded samples of deionized, tap and river water were in excess of 68%. PMID- 8365959 TI - Routine monitoring of Cryptosporidium oocysts in water using flow cytometry. AB - A flow cytometric method for the routine analysis of environmental water samples for the presence of Cryptosporidium oocysts has been developed. It uses a Coulter Epics Elite flow cytometer to examine water samples and to separate oocysts from contaminating debris by cell sorting. The sorted particles are then rapidly screened by microscopy. The method has been evaluated and compared with direct epifluorescence microscopy on 325 river, reservoir and drinking water samples. The technique was found to be more sensitive, faster and easier to perform than conventional epifluorescent microscopy for the routine examination of water samples for Cryptosporidium. PMID- 8365960 TI - Individual airway constrictor response heterogeneity to histamine assessed by high-resolution computed tomography. AB - We directly measured the range of individual airway responses to aerosol and intravenous administration of histamine by using high-resolution computed tomography and then compared the heterogeneity in constriction responses between these two routes. Seven dogs were used for a total of eleven studies. Six of the seven dogs received intravenous histamine (100-300 micrograms/min) and five of the seven dogs received aerosolized histamine (0.01-3.0 mg/ml for 5 breaths). Data were analyzed using linear regression models calculating residual mean square values for each route of histamine as a measure of variability in the change in airway size. The residual mean square values for the absolute airway size after the aerosol and intravenous histamine challenges were 17.73 and 15.42, respectively, which were not significantly different [F(331,166) = 1.15, P = 0.32]. Also, there were no significant differences when we compared the log or the percent change in airway area for the two routes of administration. We conclude that the route of histamine administration does not significantly affect the heterogeneity of airway response, suggesting that the heterogeneity observed after the histamine challenge is predominantly controlled by local mechanisms in the airways. PMID- 8365961 TI - Use of a new index to study relaxation in a vascular model of anaphylactic shock. AB - We have reported increased smooth muscle shortening ability in ragweed pollen sensitized saphenous vein (SSV). This may account for the vascular hyperreactivity of anaphylactic shock. We have now investigated relaxation in SSV. Because isotonic relaxation is load and initial contractile element length dependent, we developed an adjusted half-relaxation time index, which was independent of these variables. Muscle activation state was monitored by measuring maximum unloaded velocity. The relaxation index showed no difference between SSV and control saphenous vein after 2.5, 10, and 15 s of electrical stimulation; however, after 1 s of stimulation it was prolonged significantly in SSV. We concluded that the cross bridges activating early in contraction demonstrated prolonged relaxation. Activation state during muscle relaxation spontaneously increased toward the end of relaxation, coincident with a slowing in isotonic re-elongation rate. This was seen only in muscles relaxing from 15 s of stimulation. Our results indicate that 1) the relaxation properties of early cycling (1 s) cross bridges are altered after sensitization; and 2) toward the end of isotonic relaxation, cross-bridge cycling rate increases spontaneously, a phenomenon not previously reported. We speculate that the rapid re-elongation in late relaxation may reactivate muscle. PMID- 8365962 TI - Effect of positive end-expiratory pressure on leukocyte transit in rabbit lungs. AB - Previous experiments in humans and animals have shown that neutrophils (PMN) are delayed in the lung by the inhalation of cigarette smoke. Others have shown that cigarette smoking raises airway resistance, and it follows that this will increase the expiratory time constant of the airways. When the expiratory time constant of the airways exceeds that of the chest wall, alveolar pressure will rise and compress alveolar capillaries. To determine the effect of alveolar compression on PMN retention, we measured the arteriovenous (A-V) difference for leukocytes across the lung and determined the retention of 51Cr-labeled PMN in the lungs of anesthetized ventilated rabbits. The results show that the application of positive end-expiratory airway pressure (PEEP) produced an immediate difference for PMN across the lung, which disappeared in approximately 3 min when PEEP was continuously applied. This effect was attributed to alveolar compression rather than reduced cardiac output, because a similar A-V difference for PMN was observed in separate experiments in which cardiac output was maintained by vascular expansion during PEEP. The results also show that, when PEEP was continuously applied for approximately 30 min, it failed to increase the percent retention of either inactivated (PEEP = 14 +/- 2% vs. non-PEEP 16 +/- 3%) or activated (PEEP = 62 +/- 7% vs. non-PEEP 63 +/- 6%) 51Cr-PMN. We conclude that the application of PEEP traps PMN in compressed alveolar capillaries, creating an immediate A-V difference that disappears as blood flow is redistributed to vessels that are not compressed by PEEP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365963 TI - Intramuscular pressure and electromyography as indexes of force during isokinetic exercise. AB - A direct method for measuring force production of specific muscles during dynamic exercise is presently unavailable. Previous studies indicate that both intramuscular pressure (IMP) and electromyography (EMG) correlate linearly with muscle contraction force during isometric exercise. The objective of this study was to compare IMP and EMG as linear assessors of muscle contraction force during dynamic exercise. IMP and surface EMG activity were recorded during concentric and eccentric isokinetic plantarflexion and dorsiflexion of the ankle joint from the tibialis anterior (TA) and soleus (SOL) muscles of nine male volunteers (28 54 yr). Ankle torque was measured using a dynamometer, and IMP was measured via catheterization. IMP exhibited better linear correlation than EMG with ankle joint torque during concentric contractions of the SOL (IMP R2 = 0.97, EMG R2 = 0.81) and the TA (IMP R2 = 0.97, EMG R2 = 0.90), as well as during eccentric contractions (SOL: IMP R2 = 0.91, EMG R2 = 0.51; TA: IMP R2 = 0.94, EMG R2 = 0.73). IMP provides a better index of muscle contraction force than EMG during concentric and eccentric exercise through the entire range of torque. IMP reflects intrinsic mechanical properties of individual muscles, such as length tension relationships, which EMG is unable to assess. PMID- 8365964 TI - Hyperoxic exposure enhances airway reactivity of newborn guinea pigs. AB - To determine whether altered airway smooth muscle contractility contributes to airway hyperreactivity resulting from hyperoxic exposure, in vitro contractile responses of airways to two physiological constrictors, acetylcholine (10(-9) to 10(-4) M) and histamine (10(-8) to 10(-4) M), were examined. Extrathoracic trachea, intrathoracic trachea, and bronchus from 1- to 2-day-old (newborn) guinea pigs exposed to 85% oxygen for 84 h were compared with tissues obtained from newborns reared in room air. Responses in the presence and absence of aspirin (ASA; 10(-3) M) were compared. Hyperoxic exposure did not affect the histology of the airway epithelia. Contractile responses to acetylcholine and histamine were similar. Without ASA, maximal tensions generated were higher in both extrathoracic and intrathoracic trachea obtained from hyperoxia-exposed neonates than in trachea from newborns reared in room air. ASA caused maximal tensions of trachea from newborns reared in room air to increase but did not affect the already increased contractility of trachea from hyperoxia-exposed animals; the tensions achieved in hyperoxic tissues with and without ASA were similar to the hyperactive responses induced by ASA in tissues from animals reared in room air. Bronchi showed responses similar to those seen in tracheal segments. Thus, despite no apparent histological effect on the airway epithelium, hyperoxic exposure seems to increase airway smooth muscle contractility, is nonspecific for different constricting agents, and shows no regional differences in airway reactivity. PMID- 8365965 TI - Regulation of expiratory muscles during postnatal development in anesthetized piglets. AB - We compared maturation of the responses of the rib cage [triangularis sterni (TS)] and abdominal [transversus abdominis (TA)] expiratory muscles with each other and with the responses of the diaphragm (DIA) during hypercarbic and hypoxic stimulation. Studies were performed in anesthetized (urethan and chloralose) piglets of two age groups (< 6 days, n = 10; 14-21 days, n = 11) before and after bilateral cervical vagotomy. Hypercarbia (7% CO2-93% O2) was associated with comparable sustained increases in the minute electromyograms (EMGs) of both TS and TA, which were closely coupled to the DIA responses in both age groups. Hypoxia (12% O2-88% N2) caused a biphasic response of the minute EMG of both expiratory muscles and DIA; these biphasic responses were less prominent at 14-21 days than at < 6 days. Vagotomy caused an increase in the amplitude of both TS and TA (38 +/- 30 and 27 +/- 21%, respectively) as well as the DIA (45 +/ 16%) but did not affect their relative responses to chemostimulation. We conclude that during postnatal development 1) the rib cage and abdominal expiratory muscle responses to chemostimulation are coupled to each other and parallel those of the DIA and 2) the presence of vagal afferents attenuates the drive to both inspiratory and expiratory motoneurons under the current experimental conditions but does not influence the relative responses of expiratory muscles and DIA to hypercarbia or hypoxia. We speculate that comparable activation of inspiratory and expiratory pumping muscles serves to stabilize respiratory control in the face of altered chemosensory or vagal inputs during early postnatal life. PMID- 8365966 TI - Comparison of the secretory response of the nasal mucosa to methacholine and histamine. AB - To better understand the secretory response of the nasal mucosa, we must be able to accurately measure its physiological response. To this end, we developed a localized challenge technique using paper disks to stimulate the mucosa on one side and measure secretions from both sides to study both direct and reflex responses. Both methacholine and histamine induced a dose-dependent increase in secretion weights on the challenge side, whereas only histamine induced a contralateral reflex. Repeated stimulation with histamine, but not methacholine, resulted in tachyphylaxis. Pretreatment with atropine resulted in inhibition of the contralateral secretory response to histamine and the ipsilateral response to methacholine with only partial inhibition of the ipsilateral histamine response. Terfenadine pretreatment resulted in the complete inhibition of both the ipsilateral and contralateral responses to histamine with no effect on methacholine-induced secretions. Ipsilaterally applied lidocaine had no effect on the histamine response but, when applied contralaterally, partially inhibited that response. Topical diphenhydramine applied ipsilaterally led to significant inhibition of the ipsilateral and contralateral secretory responses to histamine but had no effect when applied contralaterally. We conclude that methacholine and histamine have different effects on the nasal mucosa. We speculate that methacholine stimulates glands directly, whereas histamine includes both direct and neurogenic stimulation. PMID- 8365967 TI - Importance of left atrial baroreceptors in the cardiopulmonary baroreflex of normal humans. AB - In animals, sympathetic responses to orthostasis are regulated in part by cardiopulmonary afferents arising from atrial and ventricular baroreceptors. To determine the relative importance of these baroreceptor regions in the cardiopulmonary baroreflex of normal humans, simultaneous measurements of left atrial and right and left ventricular volumes (cine computed tomography), invasive hemodynamics, forearm vascular resistance (plethysmography), and efferent sympathetic nerve activity to muscle (microneurography) were obtained under control conditions and with nonhypotensive lower body negative pressure ( 10 mmHg, LBNP-10) in nine normal human subjects. LBNP-10 did not alter heart rate or mean systemic arterial pressure, but it did produce significant decreases in pulmonary artery diastolic and right atrial pressures. This reduction in cardiac filling pressures resulted in efferent sympathoexcitation evidenced by increases in forearm vascular resistance and efferent sympathetic nerve activity to the muscle. LBNP-10 did not alter end-diastolic volume of the left or the right ventricle. Similarly, ventricular stroke volume was unchanged during LBNP-10, as assessed by cine computed tomography or thermodilution techniques. In contrast, LBNP-10 resulted in a significant decrease in left atrial volume. Thus, LBNP produced a significant decrease in cardiac filling pressures and left atrial volumes with resultant reflex sympathoexcitation, whereas ventricular volumes were unchanged. These observations suggest an important role for left atrial (nonventricular) baroreceptor afferents in the cardiopulmonary baroreflex of normal humans. PMID- 8365968 TI - Effects of aerosol methacholine and histamine on airways and lung parenchyma in healthy humans. AB - To investigate whether histamine (His) and methacholine (MCh) have different effects on airways and lung parenchyma, 11 healthy subjects were given aerosol MCh until a response plateau was obtained and then two doses of His. At the plateau, forced expiratory volume in 1 s and forced expiratory flow at 40% of vital capacity from partial flow-volume curves were reduced by 19 +/- 3 (SE) and 80 +/- 4%, respectively. Aerosol His decreased forced expiratory volume in 1 s by an additional 12 +/- 1% but left partial forced expiratory flow unchanged. The bronchodilator effect of deep inhalation, as inferred from the ratio of forced expiratory flow from maximal to that from partial flow-volume curves, increased after MCh and plateaued but decreased after His. Quasi-static transpulmonary pressure-volume area determined in seven subjects was unchanged after MCh but was increased by 57 +/- 10% after His. We conclude that adding His after the response to MCh plateaued does not increase the maximal degree of bronchoconstriction but may increase parenchymal hysteresis, thus blunting the bronchodilator effect of deep inhalation. These results suggest that His and MCh have similar effects on airway smooth muscle but different effects on lung tissue properties. PMID- 8365969 TI - Control of segmental upper airway resistance in patients with obstructive sleep apnea. AB - We sought to determine if the upper airway response to an added inspiratory resistive load (IRL) during wakefulness could be used to predict the site of upper airway collapse in patients with obstructive sleep apnea (OSA). In 10 awake patients with OSA, we investigated the relationship between resistance in three segments of the upper airway (nasal, nasopharyngeal, and oropharyngeal) and three muscles known to influence these segments (alae nasi, tensor veli palatini, and genioglossus) while the patient breathed with or without a small IRL (2 cmH2O.l 1.s). During IRL, patients with OSA exhibited increased nasopharyngeal resistance and no significant increase in either the genioglossus or tensor veli palatini activities. Neither nasal resistance nor alae nasi EMG activity was affected by IRL. We contrasted this to the response of five normal subjects, in whom we found no change in the resistance of either segment of the airway and no change in the genioglossus EMG but a significant activation of the tensor palatini. In six patients with OSA, we used the waking data to predict the site of upper airway collapse during sleep and we had limited success. The most successful index (correct in 4 of 6 patients) incorporated the greatest relative change in segmental resistance during IRL at the lowest electromyographic activity. We conclude, in patients with OSA, IRL narrows the more collapsible segment of the upper airway, in part due to inadequate activation of upper airway muscles. However, it is difficult to predict the site of upper airway collapse based on the waking measurements where upper airway muscle activity masks the passive airway characteristics. PMID- 8365970 TI - Surface electromyogram power spectrum in human quadriceps muscle during incremental exercise. AB - Spectral electromyographic (EMG) changes in human quadriceps muscles were studied to reinvestigate discrepant results concerning mean power frequency (MPF) changes during dynamic exercise. An incremental test consisting of a quasi-linear increase in mechanical power on a bicycle ergometer (for 20-100% of maximal aerobic power) was performed by forty subjects. During this test, surface EMGs from the quadriceps muscles showed that EMG total power (PEMG) increased with a curvilinear pattern for every subject, whereas MPF kinetics varied from one subject to another. PEMG changes had the same shape, which would lead to disappointing results in terms of discrimination between subjects. The ability of normalized MPF kinetics to define significant clusters of subjects was tested using a principal component analysis. This analysis led to the projection of all experiments onto a plane and revealed a relevant grouping of MPF profiles. Differences in MPF kinetics between clusters are interpreted in terms of various possibilities of balance between physiological events leading to an increase or a decrease in MPF. PMID- 8365971 TI - Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans. AB - This study examined the effects of branched-chain amino acid (BCAA) supplementation on amino acid and ammonia (NH3) responses during prolonged exercise in humans. Seven men cycled for 60 min at 75% of maximal O2 uptake after 45 min of either placebo (dextrose, 77 mg/kg) or BCAA (leucine + isoleucine + valine, 77 mg/kg) supplementation. Plasma samples (antecubital vein) were collected at rest and during exercise and analyzed for plasma NH3 and amino acids, whole blood glucose and lactate, and serum free fatty acids and glycerol. After BCAA administration, plasma BCAA levels increased from 375 +/- 22 to 760 +/ 80 microM (P < 0.05) by the onset of exercise and remained elevated throughout the experiment. Plasma NH3 concentrations increased continually during exercise for both trials and were higher (P < 0.05) after BCAA supplementation than after placebo administration. The mean plasma NH3 increase from rest to 60 min was 79 +/- 10 and 53 +/- 4 microM for BCAA and placebo trials, respectively. Plasma alanine and glutamine concentrations were elevated (P < 0.05) during exercise for both treatments. However, only glutamine concentrations were greater (P < 0.05) for BCAA trial than for placebo trial during exercise. There were no significant differences between treatments for glucose, lactate, free fatty acids, and glycerol or any other plasma amino acid. These data suggest that increased BCAA availability before exercise, when initial muscle glycogen is normal, results in significantly greater plasma NH3 responses during exercise than does placebo administration. PMID- 8365972 TI - Change in recruitment order of motor units in human parasternal intercostal muscles with sleep state. AB - Recruitment order of individual motor units in the early part of inspiration in parasternal intercostal muscles was observed in normal human subjects during wakefulness and non-rapid-eye-movement sleep. Electromyograms from bipolar fine wire intramuscular electrodes were recorded while the subjects lay supine in a sleep laboratory, and sleep stage was determined by polysomnography. From wakefulness to sleep there were numerous examples of shifts in order of recruitment among the low threshold units of early inspiration. There were corresponding shifts in the order of derecruitment of these units. Analysis of frequency of firing of units also suggested that the levels of excitatory input to one unit of a pair could be altered relative to the level of input of the other one. The data imply that there are at least minor differences in distribution of excitatory inputs from various sources among motoneurons of this muscle pool. PMID- 8365973 TI - Effect of theophylline on brain tissue oxygenation during normoxia and hypoxia in humans. AB - Although theophylline, an adenosine receptor antagonist, is known to reduce cerebral blood flow, little clinical attention has been paid to this adverse effect. This study was designed to examine the effect of theophylline on brain tissue oxygenation for a wide range of arterial PO2 in healthy volunteers. Partial gas pressures and O2 saturation in an artery (SaO2) and the internal jugular vein (SjO2) were simultaneously measured while subjects (n = 6) were breathing room air and then exposed to two levels of isocapnic hypoxia (arterial PO2 = 60 and 45 Torr) before and after infusion of theophylline (6 mg/kg of aminophylline). For the same levels of arterial oxygenation, jugular vein PO2 markedly dropped, by 3-5 Torr, after theophylline infusion, as did SjO2, by as much as 6-10%, under the arterial PCO2, which was slightly lower by 1-2 Torr in the theophylline study. By use of the linear regression lines obtained from the relationship between SaO2 and SjO2 in each study, it was calculated that the SjO2 with theophylline, while SaO2 was 95, 90, and 80%, was comparable to that without theophylline when SaO2 was 81, 78, and 73%, respectively. On the basis of the assumption that partial gas pressures and SjO2 reflect brain tissue oxygenation, these data suggest that the effect of theophylline on brain tissue oxygenation should not be ignored in some clinical settings. The effects of chronic administration remain to be studied. PMID- 8365974 TI - Isolated single lung perfusion in the rat: an experimental model. AB - To evaluate isolated single lung perfusion with chemotherapy in a rat lung metastasis model, we developed a model of in vivo isolated single lung perfusion. Twenty male rats were anesthetized with pentobarbital sodium (50 mg/kg) and intubated endotracheally. A left thoracotomy was performed with an operating microscope (x16 magnification), the left pulmonary artery was cannulated, and a left pulmonary venotomy was performed. Isolated left lung perfusion was performed for 10 min at 0.5 ml/min with heparinized whole blood (n = 10) or 0.9% normal saline (n = 10). Pulmonary vein effluent was collected by suction. Nineteen of the 20 (95%) animals survived isolated left single lung perfusion. Twenty-one days after isolated left lung perfusion right pneumonectomy was performed. Fifteen of the 19 animals (78%) survived right pneumonectomy. Postoperatively, animals that survived surgery recovered preoperative body weight. In vivo isolated single lung perfusion in rats is feasible with low mortality and morbidity and may be useful in the study of isolated perfusion with chemotherapy and in diverse physiological and pharmacological experiments. PMID- 8365975 TI - Muscle-fiber pennation angles are greater in hypertrophied than in normal muscles. AB - Muscle-fiber pennation angles were measured in vivo with the use of ultrasonography to investigate the relationship between fiber pennation and muscle size for 32 male subjects (from untrained subjects to highly trained bodybuilders). From the image of a B-mode ultrasonogram, fiber pennation angles and thickness of triceps brachii were determined, the former as angles between echoes from the interspaces of fascicles and from the aponeurosis of long and medial heads of triceps and the latter as the distance between the fat-muscle and muscle-bone interfaces. The pennation angles were in the range of 15 and 53 degrees for the long head and 9 to 26 degrees for the medial head, which were similar to or greater than the published and the present data on human cadavers. Significant differences were observed between normal subjects and bodybuilders in muscle thickness and pennation angles (P < 0.01), and there were significant correlations between muscle thickness and pennation angles for both long (r = 0.884) and medial (r = 0.833) heads of triceps, suggesting that muscle hypertrophy involves an increase in fiber pennation angles. PMID- 8365976 TI - Effect of aminophylline-Ca2+ blocker interaction on membrane potential of rat diaphragm fibers. AB - We studied the antagonism between aminophylline and two calcium channel blockers, nifedipine and verapamil, and its effect on the resting membrane potential of rat diaphragm fibers in vitro at 25 degrees C. Aminophylline hyperpolarizes the fibers in a dose-dependent manner, and the maximum effect is reached with 1 mM of the drug, approximately 9 mV compared with normal values. Both nifedipine and verapamil (1-5 microM) decreased the amount of hyperpolarization induced by aminophylline, and this is partially reversed when the xanthine concentration in the bath is increased. From the Hill equation we obtained a value of 2 for the slope, suggesting that two molecules of aminophylline bind to the receptor. Nifedipine modifies the affinity and the intrinsic activity of aminophylline, whereas verapamil reduces its intrinsic activity. The effect of nifedipine and verapamil is explained on the basis of the changed action of aminophylline on its site as a result of the interaction of the calcium channel blockers with their interdependent receptors. PMID- 8365977 TI - Oxygen cost of increasing tidal volume and diaphragm flattening in obstructive pulmonary disease. AB - Hypercapnia is associated with a shallow breathing pattern in patients with severe chronic obstructive pulmonary disease (COPD). We sought to determine the oxygen cost of increasing tidal volume and to relate this to hypercapnia [arterial PCO2 (PaCO2) > or = 45 Torr] and diaphragm flattening. We studied 3 normal subjects and 12 patients with stable but comparably severe COPD (forced expired volume in 1 s 1.01 +/- 0.09 liters) who had baseline PaCO2 ranging from 36 to 56 Torr. Oxygen consumption was measured during the subject's native breathing pattern and then while tidal volume was increased by 20%; minute ventilation was held constant by proportionately slowing frequency. There was a significant oxygen cost of increasing tidal volume for hypercapnic patients (235 +/- 23 to 260 +/- 25 ml O2/min; P = 0.002); no significant oxygen cost was observed in normal or eucapnic patients. This oxygen cost was positively correlated to baseline PaCO2 (r2 = 0.88, P < 0.001) and degree of diaphragm flattening assessed from chest radiographs (r2 = 0.74, P < 0.05). Although others have shown that force generation is preserved during chronic hyperinflation (G. A. Farkas and C. Roussos. J. Appl. Physiol. 54: 1635-1640, 1983; T. Similowski et al. N. Engl. J. Med. 325: 917-923, 1991), we conclude that diaphragm flattening produces mechanical inefficiency that may contribute to limiting the effective operating range of the respiratory muscles during tidal breathing. PMID- 8365978 TI - Mechanics of the parasternal intercostals in prone dogs: statics and dynamics. AB - It is well established that the parasternal intercostal muscles in supine dogs play a major role in causing the inspiratory elevation of the ribs. This posture, however, is not physiological in the dog. In the present study, we measured the electromyographic (EMG) activity and the respiratory changes in length of these muscles in the prone (standing) and supine postures in seven anesthetized spontaneously breathing dogs. With a change from the supine to the prone posture, the parasternal intercostals showed a 3.2% reduction in their relaxation length (Lr), but their mechanical behavior was essentially unchanged. Thus, the muscles continued to shorten below Lr during inspiration and to lengthen beyond Lr during expiration. With the adoption of the prone posture, the amount of parasternal inspiratory EMG activity and the amount of inspiratory muscle shortening each increased by 30-35%. Furthermore, when the parasternal intercostal in a single interspace was selectively denervated, the shortening of the muscle during inspiration in both postures was virtually eliminated. These observations indicate that in the dog the parasternal intercostals still play a major role in causing the inspiratory elevation of the ribs in the prone posture. These observations also suggest that these muscles in prone animals continue to operate on the descending limb of their length-tension curve. PMID- 8365979 TI - Transcapillary fluid responses to lower body negative pressure. AB - The effect of lower body negative pressure (LBNP) on transcapillary fluid balance is unknown. Therefore, our objective was to assess leg interstitial fluid pressures (IFP), leg circumference, plasma volume (PV), and net whole body transcapillary fluid transport (TFT) during and after supine LBNP and to evaluate the addition of oral saline ingestion on transcapillary exchange. Six healthy men 23-41 yr old underwent 4 h of 30 mmHg LBNP, followed by 50 min of supine recovery on two separate occasions, once with and once without ingestion of 1 liter of isotonic saline. IFP was measured continuously in subcutis as well as superficial and deep regions of the tibialis anterior muscle by slit catheters. TFT was calculated by subtracting urine production and calculated insensible fluid loss from changes in PV. During exposure to LBNP, IFP decreased in parallel with chamber pressure, foot venous pressure did not change, leg circumference increased by 3 +/- 0.35% (SE) (P < 0.05), and PV decreased by 14 +/- 2.3%. IFP returned to near control levels after LBNP. At the end of minute 50 of recovery, PV remained decreased (by 7.5 +/- 5.2%) and leg circumference remained elevated (by 1 +/- 0.37%). LBNP alone produced significant movement of fluid into the lower body but no net TFT (-7 +/- 12 ml/h). During LBNP with saline ingestion, 72 +/- 4% of the ingested fluid volume filtered out of the vascular space (TFT = 145 +/- 10 ml/h), and PV decreased by 6 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365980 TI - Functional significance of increased airway smooth muscle in asthma and COPD. AB - Using a computational model, we investigated the effect of the morphologically determined increased airway smooth muscle mass, adventitial mass, and submucosal mass observed in patients with asthma and chronic obstructive pulmonary disease (COPD) on the increase in airway resistance in response to a bronchoconstricting stimulus. The computational model of Wiggs et al. (J. Appl. Physiol. 69: 849-860, 1990) was modified in such a way that smooth muscle shortening was limited by the maximal stress that the muscle could develop at the constricted length. Increased adventitial thickness was found to increase constriction by reducing parenchymal interdependence. Increased submucosal thickness led to greater luminal occlusion for any degree of smooth muscle shortening. Increased muscle thickness allowed greater smooth muscle shortening against the elastic loads provided by parenchymal interdependence and airway wall stiffness. We found that for constant airway mechanics, as reflected by the passive area-pressure curves of the airways, the increased muscle mass is likely to be the most important abnormality responsible for the increased resistance observed in response to bronchoconstricting stimuli in asthma and COPD. For a given maximal muscle stress, greater muscle thickness allows the development of greater tension and thus more constriction of the lumen. PMID- 8365981 TI - Effects of tube thoracostomy on pleural fluid characteristics in sheep. AB - We studied the pleural inflammatory response to tube thoracostomy by inserting an Argyle 32-Fr tube in the pleural space of 10 anesthetized sheep. An experimental pleural effusion was created by infusion of sterile normal saline (10 ml/kg) into the pleural space, and the animals were allowed to recover. Systemic blood and experimental pleural effusion (EPE) samples were obtained at time 0, 30 min, hourly for 6 h, and at 6-h intervals for a total of 48 h. EPE white cell count rose from 125 +/- 125 to 6,323 +/- 2,268/microliters (SE) at 6 h (P < 0.05) but showed marked variability at 42 and 48 h (P < 0.05), with values ranging from 8,000 to 22,000/microliters. The systemic white cell count rose from 5,195 +/- 914 to 9,640 +/- 1,110/microliters (P < 0.01) within the first 12 h and then remained stable. EPE protein increased from 0 +/- 0 to 3.73 +/- 0.2 g/dl at 48 h (P < 0.05). EPE lactate dehydrogenase rose from 44 +/- 12 IU/l to a peak of 638 +/- 55 IU/l at 24 h (P < 0.05). EPE glucose was significantly lower than serum glucose at 36, 42, and 48 h (P < 0.05). These data indicate that chest tube placement rapidly induces significant pleural inflammation and results in formation of a sterile exudate. PMID- 8365983 TI - Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats. AB - The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis. PMID- 8365982 TI - Osmolality affects ion and water fluxes and secretion in the ferret trachea. AB - Nonisosmolar solutions were placed in the lumen of the ferret trachea in vitro in an organ bath. Hyposmolar (150 mmol/kg) solutions progressively increased in osmolarity over 1 h. Increases in luminal concentration of impermeant blue dextran occurred only after 5 min, suggesting that the initial changes were due to ion rather than water fluxes. With hyperosmolar solutions the osmolarity decreased over 1 h with no change in blue dextran concentration, indicating that ion but not water fluxes were taking place. Cooling the preparation to 4 degrees C greatly reduced the osmolaity changes with hyperosmolar solutions and halved those with hyposmolar solutions, suggesting that active ion transport was involved. Hyposmolar (75-150 mmol/kg) and hyperosmolar (450-900 mmol/kg) solutions both increased albumin output into the lumen, but the response was prevented by cooling the trachea to 4 degrees C. Hyposmolar and hyperosmolar solutions both increased the output of lysozyme from glandular serous cells into the lumen. The response to hyposmolar solutions was stronger. Cooling the trachea abolished the lysozyme response to hyperosmolar solutions. Thus hypo- and hyperosmolar solutions promote ion transport in directions to restore isosmolarity. Both nonisosmolar solutions promote albumin movement by active transport across the mucosa and lysozyme secretion from submucosal glands, responses inhibited by tracheal cooling and therefore dependent on metabolically active processes. PMID- 8365984 TI - Pontile regulation of ventilatory activity in the adult rat. AB - Our purpose was to characterize the pontile components of the brain stem ventilatory control system in rats. This study was precipitated by reports that this pontile component might differ fundamentally from that of other species. Efferent activity of the phrenic nerve was recorded in anesthetized, vagotomized, paralyzed, and ventilated adult rats. As in other species, electrical stimulations of the rostral pons caused premature terminations and/or onsets of phrenic activity in eupnea. Electrolytic lesions of rostrolateral pons resulted in apneusis, characterized by significant prolongations of the phrenic burst. Some effective lesions were in the region of the nucleus parabrachialis medialis and the Kolliker-Fuse nucleus, the site of the pneumotaxic center. Other lesions resulting in apneusis were ventral to the pneumotaxic center. As in cats, lesions in the caudal pontile reticular formation caused the duration of the apneustic neural inspiration to return toward that of eupnea. Again, as in other species, gradual alterations from eupnea to gasping in the rat were recorded during hypoxia, which was induced by ventilation with carbon monoxide. We conclude that the brain stem respiratory control system is similarly organized in rats and other mammalian species. These results have implications for contemporary hypotheses concerning the neurogenesis of ventilatory activity. PMID- 8365985 TI - Depletion of alveolar macrophages by liposome-encapsulated dichloromethylene diphosphonate. AB - Alveolar macrophages (AM) play an important role in lung biology. In this study, we demonstrated that tracheal insufflation of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposome) selectively depleted AMs in rats. Insufflation of a single dose of Cl2MDP-liposomes (80 microliters containing 1.34 mumol of Cl2MDP) but not liposomes containing phosphate-buffered saline resulted in > 70% depletion of AMs starting within 1 day and lasting for > 5 days after insufflation. There was a slight but significant intraalveolar inflammatory response. Insufflation of Cl2MDP also resulted in depletion of AMs; however, it caused cytoplasmic edema of alveolar epithelial cells as well. Depletion of AMs by Cl2MDP-liposomes markedly reduced the endotoxin-induced neutrophil (polymorphonuclear lymphocyte) recruitment and the release of tumor necrosis factor into the alveolar space, suggesting that endotoxin-induced neutrophil recruitment and tumor necrosis factor release were dependent on AMs. This AM-depleted animal model will be useful for studying the in vivo functions of AMs and their role in various physiological and pathological conditions. PMID- 8365986 TI - Central and peripheral diaphragmatic fatigue in loaded normal and vagotomized dogs. AB - Severe inspiratory elastic load terminated by respiratory arrest (RA) was studied in 24 anesthetized dogs (group 1, normal: n = 14; group 2, vagotomized: n = 10). The peripheral and central components of the decrease in diaphragmatic force generation and the events preceding RA were studied. We measured stimulated tetanic transdiaphragmatic pressure (Pdi), single twitch compound action potentials, integrated diaphragmatic electromyographic activity (iEMGdi), respiratory frequency (f), inspiratory time, inspiratory drive, overall diaphragmatic activation, and Pdi single twitch superimposed over peak Pdi. Imposed target pressure was -68.8 +/- 4.37 cmH2O for group 1 and -70.9 +/- 4.19 cmH2O for group 2, and the tension-time index of the diaphragm was the same for both groups (0.22 +/- 0.010). During load, 1) f increased in group 1 from 25.4 +/ 1.33 to 41.3 +/- 4.66 cycles/min, and tachypnea was prevented by vagotomy; 2) twitch occlusion persisted until RA and compound action potentials did not change; 3) iEMGdi and inspiratory drive increased and remained high until RA; 4) overall diaphragmatic activation increased 514 (group 1) and 260% (group 2) and then decreased to 228% of the basal value 10 s before RA in group 1 because of a fall in f; and 5) after RA, Pdi stimulated at 60 Hz fell to 39 (group 1; P < 0.0025) and 51% (group 2; NS with group 1) of the basal value. In summary, 1) peripheral fatigue developed without transmission failure; 2) diaphragmatic activation remained maximal until RA; 3) the fall in f appeared as a preterminal event only in group 1; and 4) vagus nerves are necessary for load-induced tachypnea. PMID- 8365987 TI - Theory and measurements of snores. AB - Upper airway narrowing, collapsibility, and resistance are recognized predisposing factors for snoring and obstructive sleep apnea, but the mechanisms of their action and interaction are not known. We studied a simple theoretical model of the upper airways, consisting of a movable wall in a channel segment that connects to the airway opening via a conduit with a resistance. Inspiratory flow (V) through the channel segment causes local pressure changes due to viscous losses and the Bernoulli force that may overcome the elastic forces acting on the movable wall. The model predicts instability leading to upper airway closure over a wide range of parameter values. Increasing inspiratory V above a boundary, determined by values of upper airway resistance, segment compliance, length, width, and diameter, as well as gas density, leads to a dynamic airway closure. The mathematical model establishes the power relationships between parameters and provides physiologically realistic quantitative simulation of upper airway closure when values are adapted from literature and from radiographic measurements of upper airway motion induced by negative pressure. The rate of appearance of repetitive sound structures during snoring was favorably compared with the model's prediction of the time course of wall motion during collapse. V measurements during simulated snores revealed an asymmetric oscillatory pattern compatible with repetitive upper airway closure. We conclude that snoring may be modeled as a series of dynamic closure events of the upper airways. The model predicts that the width and length of the movable portion of the upper airways and the gas density are likely to affect the onset of snoring, in addition to other, previously recognized, parameters. PMID- 8365988 TI - How changes in the serial distribution of bronchoconstriction affect lung mechanics. AB - It is generally accepted that methacholine (MCh) acts predominantly on the central airways and histamine (H) acts on the lung periphery. We hypothesized therefore that lung mechanics would be affected differently by H and MCh aerosols. In 12 anesthetized paralyzed open-chest mongrel dogs, we obtained MCh (0.1-30 mg/ml, n = 6) and H (0.1-30 mg/ml, n = 6) concentration-response curves. The alveolar capsule technique was used to partition lung resistance (RL) into airway (Raw) and tissue (Rti) components. The degree of mechanical heterogeneity across the lung was assessed by computing the coefficient of variation for five alveolar pressures during relaxed expirations. RL increased 823 +/- 202% after H and 992 +/- 219% after MCh. Rti increased 784 +/- 192% after H and 1,014 +/- 279% after MCh. Raw increased 1,098 +/- 297% after H and 1,275 +/- 332% after MCh. Elastance increased 342 +/- 53% after H and 423 +/- 88% after MCh. The coefficient of variation increased 279 +/- 65% after H and 252 +/- 55% after MCh. The patterns of change were similar throughout the H and MCh concentration response curves. We conclude that H and MCh have comparable effects on lung mechanics and that the degree and pattern of heterogeneity inside the lung after constriction are the same regardless of the agent used. These data support the hypothesis that H and MCh have some similar direct effect on the lung parenchyma. Parenchymal deformation after MCh-induced central airway constriction alone would be unlikely to explain increases in Rti of this magnitude or changes in lung mechanics so similar to those induced by H. PMID- 8365989 TI - Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction. AB - Mechanical interdependence between airways and tissues can modify the magnitude of induced bronchoconstriction. We questioned whether the guinea pig, an animal with abundant airway smooth muscle, would differ from other species in the relative responsiveness of and interactions between airways and tissues. Therefore we induced constriction with aerosolized methacholine (MCh) and partitioned responses into airway and tissue components. We measured tracheal and alveolar pressures using alveolar capsules in open-chest guinea pigs (n = 9) during mechanical ventilation [frequency = 1 Hz, tidal volume = 6 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) before and after administration of aerosols of MCh in progressively doubling concentrations (0.063-16 mg/ml). In separate animals (n = 10), measurements were made at 3-13 cmH2O PEEP. After aerosols of saline and MCh (0.125-32 mg/ml), measurements were repeated at 3, 7, and 11 cmH2O PEEP. At submaximal levels of constriction, the airways and lung tissues demonstrated similar responsiveness. Increasing PEEP increased RL and Rti and decreased Raw under baseline conditions. At low concentrations of MCh, increasing PEEP increased RL but decreased RL at the highest concentration. Increases in PEEP significantly increased Rti at all concentrations of MCh but decreased Raw only at 8 mg/ml of MCh. These observations demonstrate that, in guinea pigs, during submaximal constriction, airways and tissues behave similarly; moreover, airway-parenchymal interdependence is important in determining the level of bronchoconstriction. PMID- 8365990 TI - Recovery of muscle power after high-intensity short-term exercise: comparing boys and men. AB - This study was conducted to determine whether boys differ from men in their ability to recover from high-intensity exercise. Two groups of volunteers, 8 prepubertal boys (9-12 yr) and 8 young men (19-23 yr), were similar in their peak oxygen uptake (49.6 +/- 6.6 vs. 51.1 +/- 6.6 ml.min-1 x kg-1), adiposity, and activity levels. On three different occasions subjects performed two consecutive 30-s all-out cycling tasks [Wingate anaerobic test (WAnT)], separated by a 1-, 2 , or 10-min recovery interval. In the boys, mean power reached 89.9 +/- 3.6% of the initial value after 1 min of recovery, 96.4 +/- 2.3% after 2 min, and 103.5 +/- 1.3% after 10 min. For the men, the values were 71.2 +/- 2.6, 77.1 +/- 2.4, and 94.0 +/- 1.3%, respectively (boys vs. men, P < 0.0001). Relative to the external work performed during the first WAnT, the boys had a higher net oxygen uptake (exercise--resting) during the test than the men (83.8 +/- 18.4 vs. 57.8 +/- 6.1 ml/kJ). After the WAnT, the net CO2 output and the respiratory exchange ratio were lower in the boys, and they recovered faster. It was concluded that boys recover faster than men from high-intensity short-term exercise. This may reflect a lower reliance on glycolysis during the WAnT in the boys, leading to less acidosis. It is also possible that the boys had a faster postexercise removal of metabolites. PMID- 8365991 TI - Spine and total body bone mineral density in amenorrheic endurance athletes. AB - Lumbar spine, total body, and regional bone mineral densities (BMDs) were measured in eumenorrheic and amenorrheic runners and triathletes by using dual energy X-ray absorptiometry (Lunar DPX). Values were also compared with age- and weight-matched reference data from the Lunar British database. The amenorrheic group had significantly lower lumbar spine (P = 0.003), arm (P = 0.018), trunk (P = 0.014), and total spine (P < 0.0001) BMDs compared with the eumenorrheic group and significantly lower lumbar (P = 0.002) and total spine (P < 0.001) values compared with the reference controls. Leg (P = 0.009) and arm (P < 0.001) densities were significantly higher than controls. All regions, apart from the lumbar spine, were significantly higher in the eumenorrheic group compared with the reference group. There were no within-group differences for the runners and triathletes. Compared with the eumenorrheic athletes, the amenorrheic women had significantly later age of menarche (P = 0.0032). The type of physical activity undertaken by these athletes can compensate for the loss of menses at the majority of skeletal sites with the exception of the spine. PMID- 8365992 TI - Role of glucose and insulin loads to the exercising limb in increasing glucose uptake and metabolism. AB - To assess the contributions of glucose load to the working hindlimb and local contraction-related events (changes related to the microvasculature and/or intrinsic muscle metabolic properties) to the exercise-induced increases in muscle glucose uptake and metabolism in vivo, dogs were studied with somatostatin infused to suppress insulin release, and glucose and insulin were replaced 1) during rest and treadmill exercise at rates that recreate limb glucose and insulin loads evident during exercise (n = 5), 2) at rest to selectively normalize the limb glucose load to rates present during exercise while retaining basal limb insulin loads (GL, n = 5), or 3) at rest to normalize both the limb glucose and insulin loads to those present during exercise (IGL, n = 5). Limb arteriovenous difference and isotopic ([U-14C]glucose) techniques were used to quantify muscle glucose uptake and metabolism. Limb glucose load rose from 819 +/ 141 mumol/min in the basal state to 1,568 +/- 190 mumol/min with exercise. Limb glucose loads were 1,423 +/- 88 and 1,502 +/- 165 mumol/min in GL and IGL. The limb insulin load rose from basal rates of 12.9 +/- 2.3 to 22.9 +/- 5.9 nmol/min during exercise. Limb insulin loads were similar to basal loads in GL (8.8 +/- 1.9 nmol/min) and exercise in IGL (28.2 +/- 5.5 nmol/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365993 TI - Disruption of pulmonary surfactant's ability to maintain openness of a narrow tube. AB - Pulmonary surfactant stabilizes alveoli but, by maintaining patency of peripheral conducting airways, will also lower resistance to airflow. A small quantity of a surfactant suspension (3 mg/ml) formed a blocking liquid column in a narrow section of a glass capillary. Pressure was raised on one side of that column, whereby it was forced to move out of the narrow section, and it did not return but left the capillary open for a free airflow. The surfactant capability to maintain free airflow was lost with the addition of albumin (> 10 mg/ml) or fibrinogen (> 0.5 mg/ml). Surfactant function was seriously affected by hydrolysis with phospholipase C but not with phospholipase A2. With a small quantity of albumin added (5 mg/ml), the ability to maintain openness was seriously affected at temperatures below 25 degrees C. An inflammatory reaction due to atopy, infection, or inhalation of irritating gases characterizes a variety of airway diseases, including asthma. If the in vitro studies can be transferred to in vivo conditions, surfactant dysfunction might contribute to certain types of airway disease. PMID- 8365994 TI - Reflex cardiovascular effects of continuous prostacyclin administration into an isolated in situ lung in the dog. AB - Bolus administration of prostacyclin (PGI2), an inflammatory product produced by the arachidonic acid cyclooxygenase pathway, into the pulmonary circulation is known to stimulate pulmonary C-fibers and to produce transient reflex cardiovascular depression. We used an isolated perfused in situ left lung preparation to examine the reflex cardiovascular effects of continuous administration of PGI2 into the isolated pulmonary circulation of dogs. PGI2 was infused for 30 min (5 micrograms.kg-1 x min-1) into the innervated isolated left pulmonary circulation in six dogs and into the denervated isolated circulation in seven dogs. Mean arterial pressure and cardiac output were significantly decreased from baseline values during the final 20 min of PGI2 infusion. There were no significant changes in maximum rate of change of left ventricular pressure during systole and in heart rate. All variables returned to baseline levels within 15 min of discontinuation of PGI2 infusion. PGI2 infusion produced no significant measured hemodynamic changes in the denervated group. Control experiments demonstrated that the observed response was not affected by duration of the preparation, lung denervation, or infusion vehicle. These findings suggest that continuous infusion of PGI2 into the isolated pulmonary circulation produces sustained cardiovascular depression via a vagal reflex mechanism that is probably mediated by pulmonary C-fibers. PMID- 8365995 TI - Effect of hindlimb unweighting on single soleus fiber maximal shortening velocity and ATPase activity. AB - This study characterizes the time course of change in single soleus muscle fiber size and function elicited by hindlimb unweighting (HU) and analyzes the extent to which varying durations of HU altered maximal velocity of shortening (Vo), myofibrillar adenosinetriphosphatase (ATPase), and relative content of slow and fast myosin in individual soleus fibers. After 1, 2, or 3 wk of HU, soleus muscle bundles were prepared and stored in skinning solution at -20 degrees C. Single fibers were isolated and mounted between a motor arm and a transducer, and fiber force, Vo, and ATPase activity were measured. Fiber myosin content was determined by one-dimensional sodium dodecyl sulfate- (SDS) polyacrylamide gel electrophoresis. After 1, 2, and 3 wk of HU, soleus fibers exhibited a progressive reduction in fiber diameter (16, 22, and 42%, respectively) and peak force (42, 48, and 72%, respectively). Peak specific tension was significantly reduced after 1 wk of HU (18%) and showed no further change in 2-3 wk of HU. During 1 and 3 wk of HU, fiber Vo and ATPase showed a significant increase. By 3 wk, Vo had increased from 1.32 +/- 0.04 to 2.94 +/- 0.17 fiber lengths/s and fiber ATPase from 291 +/- 16 to 1,064 +/- 128 microM.min-1 x mm-3. The percent fibers expressing fast myosin heavy chain increased from 4% to 29% by 3 wk of HU, and Vo and ATPase activity within a fiber were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8365996 TI - Neurocirculatory consequences of negative intrathoracic pressure vs. asphyxia during voluntary apnea. AB - To investigate the mechanisms responsible for fluctuations in arterial pressure and sympathetic nerve activity that occur during obstructive sleep apnea, we studied neurocirculatory responses to Mueller maneuvers and breath holds in conscious humans. During 20-s Mueller maneuvers at -40 mmHg, mean arterial pressure fell initially (-11 +/- 3 mmHg) and then rose above baseline (+8 +/- 3 mmHg) on release of the inspiratory strain. Sympathetic outflow to skeletal muscle was almost completely suppressed during the initial moments of the maneuver and rose to more than three times the baseline level at the termination of the maneuver. Simple 20-s breath holds were accompanied by time-dependent increases in both arterial pressure (+11 +/- 3 mmHg) and sympathetic nerve activity (> 3 times baseline). The administration of supplemental O2 greatly attenuated the increases in arterial pressure and sympathetic nerve activity during Mueller maneuvers and breath holds. We conclude that carotid chemoreflex stimulation is the primary mechanism responsible for apnea-induced sympathetic activation during wakefulness and that it may contribute importantly to the sympathetic activation that accompanies sleep-disordered breathing. PMID- 8365997 TI - Relations between muscle soreness and biochemical and functional outcomes of eccentric exercise. AB - Correlations between functional and biochemical outcomes of eccentric exercise and between these outcomes and "delayed-onset muscle soreness" (DOMS) were studied. Maximal isotonic force, extension and flexion angle of the elbow, creatine kinase activity, and myoglobin concentration in serum were measured in 27 male subjects during 5 days after 120 maximal eccentric contractions of the forearm flexors. Significant correlations were found between values at 1 to 96 h after exercise for force (r = 0.55 to 0.96), flexion (0.52 to 0.94), extension (0.41 to 0.95), and myoglobin (0.55 to 0.97) and at 24 to 96 h for creatine kinase (0.67 to 0.96) and DOMS (0.45 to 0.72). Clusters of significant correlations (0.32 to 0.91) were found among all functional and biochemical measures. DOMS, however, showed only few and lower correlations with the other parameters (0.34 to 0.63). These results can practically be interpreted as follows: 1) subjects need more time to recover completely when early deviations after eccentric exercise are large, 2) a large change in one measure is accompanied by large deviations in other measures, and 3) objective outcomes of eccentric exercise are more accurate parameters than a DOMS score for use in effect studies. PMID- 8365998 TI - Mucociliary clearance of inhaled particles measured at 2 h after ozone exposure in humans. AB - Acute exposure of humans to ozone is known to acutely cause pulmonary function decrements, inflammation, and increased permeability of pulmonary epithelium. A single study in humans has also shown that mucociliary transport increases during acute ozone exposure. Because different responses have shown a different time course of recovery after exposure, it was important to examine mucociliary transport at a different time after the cessation of ozone exposure. We exposed 15 healthy male and female nonsmoking subjects, on different occasions, to clean air and 0.4 ppm ozone for 1 h while they exercised continuously. Pulmonary function was measured immediately before and after exposure and 90 min and 24 h after exposure. Between 2 and 5 h after each exposure, retention of inhaled 5 microns mass median aerodynamic diameter 99mTc-labeled Fe2O3 particles was measured. Each subject returned the next day for a final particle retention measurement. Despite significant changes in pulmonary function, there was no difference in mean whole lung retention time of particles between clean air [77.9 +/- 0.8 (SE) min] and ozone (78.0 +/- 0.8 min) exposures, indicating that mucociliary transport is unaffected by ozone exposure when it is measured 2 h after exposure. PMID- 8365999 TI - Carbohydrate feedings and exercise performance: effect of initial muscle glycogen concentration. AB - To determine whether the ergogenic benefits of carbohydrate (CHO) feedings are affected by preexercise muscle glycogen levels, eight cyclists performed four self-paced time trials on an isokinetic ergometer over a simulated distance of 70 km. Trials were performed under the following preexercise muscle glycogen and beverage conditions: 1) high glycogen (180.2 +/- 9.7 mmol/kg wet wt) with a CHO beverage (HG-CHO), 2) high glycogen (170.2 +/- 10.4 mmol/kg wet wt) with a non CHO beverage (HG-NCHO), 3) low glycogen (99.8 +/- 6.0 mmol/kg wet wt) with a CHO beverage (LG-CHO), and 4) low glycogen (109.7 +/- 5.3 mmol/kg wet wt) with a non CHO beverage (LG-NCHO). The CHO drink (ingested at the onset of exercise and every 10 km thereafter) provided 116 +/- 6 g CHO/trial and prevented the decline in serum glucose observed during both NCHO trials. Performance times ranged from 117.93 +/- 1.44 (HG-CHO) to 122.91 +/- 2.46 min (LG-NCHO). No intertrial differences (P > 0.05) were observed for O2 consumption (75% of maximal O2 consumption), power output (237 W), or self-selected pace (8.44 min/5 km) during the initial 71-79% of exercise. Over the final 14% of the time trial, power output and pace (231 W and 8.62 min/5 km) were similar for the HG-CHO, HG-NCHO, and LG-CHO conditions, but both variables were significantly lower during the LG NCHO trial (198 W and 9.67 min/5 km, P < 0.05 vs. all other trials).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366000 TI - Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. AB - Pharmacological manipulation of brain serotonergic [5-hydroxytryptamine (5-HT)] activity affects run time to exhaustion in the rat. These effects may be mediated by neurochemical, hormonal, or substrate mechanisms. Groups of rats were decapitated during rest, after 1 h of treadmill running (20 m/min, 5% grade), and at exhaustion. Immediately before exercise rats were injected intraperitoneally with 1 mg/kg of quipazine dimaleate (QD; a 5-HT agonist), 1.5 mg/kg of LY 53857 (LY; a 5-HT antagonist), or the vehicle (V; 0.9% saline). LY increased and QD decreased time to exhaustion (approximately 28 and 32%, respectively; P < 0.05). At fatigue, QD animals had greater plasma glucose, liver glycogen, and muscle glycogen concentrations but lower plasma free fatty acid concentration than did V and LY animals (P < 0.05). In general, plasma corticosterone and catecholamine levels during exercise in QD and LY rats were similar to those in V rats. Brain 5 HT and 5-hydroxyindole-3-acetic acid concentrations were higher at 1 h of exercise than at rest (P < 0.05), and the latter increased even further at fatigue in the midbrain and striatum (P < 0.05). Brain dopamine (DA) and 3,4 dihydroxyphenylacetic acid (DOPAC) were higher at 1 h of exercise (P < 0.05) but were similar to resting levels at fatigue. QD appeared to block the increase in DA and DOPAC at 1 h of exercise, and LY prevented the decrease in DA and DOPAC at fatigue (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366001 TI - Apnea threshold and breathing rhythmicity in newborn lambs. AB - This study was designed to determine the effect of the removal of chemical stimuli on breathing rhythmicity in awake newborn lambs; it was also designed to define the chemical threshold below which breathing would stop [arterial PCO2 (PaCO2) apnea threshold]. We used a technique of graded extracorporeal CO2 removal with apneic oxygenation in three groups of animals according to age and carotid body (CB) integrity: < 2 days, CB intact (n = 5); 12 days, CB intact (n = 7); and 12 days, CB denervated (CBD; n = 5). In all animals, whatever their age and CB status, suppression of the chemical drive resulted in sustained apnea. The study, performed at four constant levels of oxygenation (hyperoxia, normoxia, moderate hypoxia, and severe hypoxia), allowed precise determination of the PaCO2 apnea threshold. We found that this PaCO2 apnea threshold depended on the degree of postnatal maturation (it was higher in the younger lambs), the level of arterial oxygenation (it was lowered by hypoxia), and CB status (it was higher in CBD animals). Moreover, we found that the 12-day-old CBD lambs breathe at a level of PaCO2 set close to the point of apnea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366002 TI - Possible role of pulmonary blood volume in chronic hypoxic pulmonary hypertension. AB - Chronic hypoxia increases the total blood volume (TBV) and pulmonary arterial blood pressure (Ppa) and induces pulmonary vascular remodeling. The present study was undertaken to assess how the pulmonary blood volume (PBV) changes during hypoxia and the possible role of PBV in chronic hypoxic pulmonary hypertension. A novel method has been developed to measure the TBV, PBV, and Ppa in conscious rats. The method consists of chronic implantation of a loose ligature around the ascending aorta and pulmonary artery, so that when the ligature is drawn tightly, it traps the blood in the pulmonary vessels and left heart and simultaneously kills the rat. The pulmonary veins are then ligated to separate the left ventricular blood volume from the PBV. This surgical approach, together with chronic catheterization of the pulmonary artery and the use of 51Cr-labeled red blood cells, allows measurement of TBV, PBV, and Ppa. This method has been used to analyze the relationships between TBV and PBV and between Ppa or right ventricular hypertrophy and PBV in two rat strains with markedly different TBV and Ppa responses to chronic hypoxia. PBV per given lung weight did not increase and even decreased during hypoxia despite marked increases in TBV. There was a close correlation between Ppa or right ventricular hypertrophy and PBV in the two strains of chronically hypoxic animals, suggesting that a greater PBV plays a significant role in the development of severe chronic hypoxic pulmonary hypertension in the altitude-susceptible Hilltop rats. PMID- 8366003 TI - Compartmentalization of the acute cytokine response in humans after intravenous endotoxin administration. AB - Lung cytokine production was examined after the intravenous administration of endotoxin to 23 normal human subjects. Bronchoalveolar lavage (BAL) was performed 7 days before and 1.5 or 5 h after endotoxin (4 ng/kg). Cytokine mRNA was evaluated in cell pellets (> 98% macrophages) by use of reverse transcription and the polymerase chain reaction. Immunoreactivity was measured by enzyme-linked immunosorbent assay of 20- to 40-fold concentrated BAL. Interleukin- (IL) 8 was detected in BAL (4-130 pg/ml) but not in the serum at baseline. Few neutrophils were found in BAL (< 1%) despite this IL-8 gradient. Peak serum IL-8 levels occurred 2 h after endotoxin (3,930 +/- 241 pg/ml), but BAL neutrophils and IL-8 did not increase. Peak serum tumor necrosis factor (TNF) levels occurred 1.5 h after endotoxin (1,844 +/- 210 pg/ml), but TNF was detected in only 1 of 20 BAL samples. TNF and IL-8 mRNA were detected by polymerase chain reaction in > 70% of the BAL samples before endotoxin, whereas IL-1 alpha, IL-1 beta, and IL-6 were detected in < 25% of the BAL samples. After endotoxin, no change was detected in cytokine mRNA expression. Actinomycin D treatment of the BAL did not alter the pattern of cytokine mRNA expression. These data suggest that mechanisms exist to insulate the alveolar space from the stimulatory effects of endotoxin and high circulating levels of cytokines. Additional factors appear to control the chemotactic effects of IL-8 on neutrophils in the air spaces during acute systemic inflammation. PMID- 8366004 TI - Does baseline airway caliber affect measurements of airway responsiveness to histamine. AB - Considerable controversy exists over the influence of baseline airway caliber on indexes of bronchial responsiveness in asthma. To directly investigate this, we used inhaled methacholine to alter baseline airway caliber to determine whether this altered the airway response to subsequent bronchoprovocation with inhaled histamine. Seventeen stable asthmatic subjects were studied; their median age was 22 yr, baseline forced expiratory volume in 1 s (FEV1) was 101.5 +/- 3.7% (SE) predicted, and geometric mean provocative concentration of inhaled methacholine causing a 20% fall in FEV1 (PC20) was 0.87 mg/ml. Initially the time course of bronchoconstriction to inhaled methacholine was determined. Subsequently the airway response to inhaled histamine administered as a single concentration was determined, both before and after reductions in baseline FEV1 by saline or methacholine of 0, 15, 25, and 35%, on 4 separate days. Altering baseline airway caliber had no effect on the subsequent response of the airways to inhaled histamine when calculated as percent fall from the new baseline. The power of the study to detect an effect of altering baseline FEV1 on the measured PC20 histamine of 0.5 doubling dilutions was > 55%, and the power to detect an effect of 1.0 doubling dilutions was > 98%. PMID- 8366005 TI - Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung. AB - Neutrophils [polymorphonuclear leukocytes (PMNs)] are sequestrated in the lung capillary bed because PMNs are delayed with respect to red blood cells (RBCs) as they pass through these microvessels. The present study examines circulating PMN size in relation to the distribution of capillary segment diameters in human, dog, and rabbit lungs and compares the shape of PMNs in suspension to that found within the pulmonary capillaries. The data show that 61, 67, and 38% of the capillary segments are narrower than the mean diameter of spherical PMNs in the rabbit, dog, and human, respectively. They also show that PMNs deform from a spherical to an ellipsoid shape in the pulmonary capillaries of all three species. These findings are consistent with previous studies showing that the pulmonary circulation restricts the passage of PMNs through the lungs and suggest that PMNs are delayed because they must deform to pass through restrictions encountered in the pulmonary capillary bed. We conclude that the discrepancy between PMN and pulmonary capillary size and the decreased deformability of PMNs with respect to RBCs are major determinants of the delay that PMNs experience with respect to RBCs in the pulmonary circulation. PMID- 8366006 TI - Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt. AB - This study investigates cerebral blood flow (CBF) velocity in humans before, during, and after 24 h of 6 degree head-down tilt (HDT), which is a currently accepted experimental model to simulate microgravity. CBF velocity was measured by use of the transcranial Doppler technique in the right middle cerebral artery of eight healthy male subjects. Mean CBF velocity increased from the pre-HDT upright seated baseline value of 55.5 +/- 3.7 (SE) cm/s to 61.5 +/- 3.3 cm/s at 0.5 h of HDT (P < 0.05), reached a peak value of 63.2 +/- 4.1 cm/s at 3 h of HDT, and remained significantly above the pre-HDT baseline for > or = 6 h of HDT. During upright seated recovery (1-5 h post-HDT), mean CBF velocity decreased to 87% of the pre-HDT baseline value (P < 0.05). Mean CBF velocity correlated well with calculated intracranial arterial pressure (IAP) (r = 0.54, P < 0.001). As analyzed by linear regression, mean CBF velocity = 29.6 + 0.32IAP. These results suggest that HDT increases CBF velocity by increasing IAP during several hours after the onset of microgravity. Importantly, the decrease in CBF velocity after HDT may be responsible, in part, for the increased risk of syncope observed in subjects after prolonged bed rest and also in astronauts returning to Earth. PMID- 8366007 TI - Differential modulation by extracellular ATP of carotid chemosensory responses. AB - The possibility that the carotid body has ATP surface receptors that mediate O2 chemoreception was tested. To distinguish between the event(s) initiating chemoreception and those at the neurotransmitter level, we also tested the chemosensory response to nicotine before and after ATP administration. Carotid bodies from cats anesthetized with pentobarbital sodium were perfused and superfused in vitro with modified Tyrode solution (PCO2 < 1 Torr, pH 7.4, 36 degrees C) equilibrated at PO2 > 400 or approximately 150 Torr while chemosensory discharge was recorded extracellularly. ATP and adenosine 5'-[gamma thio]triphosphate stimulated discharge with similar dose dependence, whereas adenosine had little effect. ATP infusion for > or = 2 min evoked an initial stimulation of discharge followed by a decline to baseline (desensitization). Desensitization did not affect the response to hypoxia (perfusate flow interruption) but inhibited the response to nicotine (4-nmol pulse). Therefore, 1) the carotid body has surface ATP receptors that may mediate the chemosensory response to nicotine but not to hypoxia and 2) nicotinic receptors are not required for carotid body O2 chemoreception. PMID- 8366008 TI - Measurement of gastric and diaphragmatic height during slow breathing maneuvers. AB - Changes in height of the gastric air bubble can be inferred, in theory, from the difference between gastric pressures measured with water- and air-filled balloon catheter systems. We describe an apparatus that satisfactorily measures changes in height of gastric balloons in vitro. During slow breathing maneuvers in standing subjects, the apparatus measured changes in height of the balloons in the stomach that were consistent with expected changes in height of the diaphragmatic dome. In four subjects, balloon movements were nearly always less than movements of the costal margin of the diaphragmatic dome observed by ultrasonography; the average ratio of height changes was 0.73. We conclude that changes in height of the diaphragmatic dome can be measured with this method during slow breathing maneuvers in upright subjects. PMID- 8366009 TI - Construction and uses of a concentric catheter for gas sampling in lung airways. AB - A catheter for intra-airway sampling of gas concentrations was constructed from concentric polyethylene tubes. The internal tube (0.58 mm ID, 0.91 mm OD) was connected to a gas analyzer while the external tube (1.20 mm ID, 1.75 mm OD) was constantly flushed by air or a calibration gas, except during sampling. Injection and sampling dead spaces were 0.35 and 0.28 ml, respectively. Delay at 4-ml/min sampling rate was 4.0 +/- 0.2 s. The 0-90% step response to a sudden change in gas composition was 0.24 s when connected to a mass spectrometer. This catheter was used to assess tracer gas dispersion during oscillatory flow (1-20 Hz) in a straight long tube. Local concentrations measured through the catheter, after a small bolus of tracer gas was injected through the external tube, compared favorably with direct measurements through needles inserted via the tube wall and with theoretical predictions. The catheter was also used to measure intra-airway gas concentrations in dog airways during spontaneous breathing, conventional mechanical ventilation, high-frequency ventilation, high-frequency vibration ventilation, and constant-flow ventilation. It ws placed by a fiber-optic bronchoscope and used to measure local quasi-steady concentrations of CO2 and local dispersion with the bolus method. The occurrence of catheter clogging with secretions was substantially reduced with flow through the external tube. Transmitting a calibration gas through the external tube facilitated in situ recalibration of the gas analyzer without removing the catheter. The use of this catheter improved the efficiency and accuracy of measurements of gas concentrations inside lung airways. PMID- 8366010 TI - Effect of peak inspiratory pressure on the filtration coefficient in the isolated perfused rat lung. AB - Positive inspiratory pressure- (PIP) ventilated, isolated rat lungs become edematous when perfused at rates approximately the normal cardiac output. The study was conducted to test the hypothesis that high peak inspiratory pressures contribute to the edema development. Five isolated lungs were perfused at a rate of 24.4 +/- 2.2 ml.min-1.100 g body wt-1 with 40% whole blood (diluted with saline containing 4.0 g/100 ml bovine serum albumin) and ventilated with peak pressures ranging from 0 to 20 mmHg. The lungs exhibited edema at PIP values > 9.3 mmHg. The stable pulmonary vascular pressure and resistance suggested that the edema may have resulted from a PIP-induced increase in microvascular permeability. In a second study, the stability of the preparation was evaluated during a 3-h test period. Seven lungs were ventilated at a peak inspiratory pressure of 8.0 mmHg and perfused at 26.8 +- 1.7 ml.min-1 x 100 g body wt-1. Microvascular integrity was maintained for approximately 2 h as indicated by filtration coefficient measurements of 0.175 +/- 0.068, 0.197 +/- 0.066, and 0.169 +/- 0.067 g.min-1 x mmHg-1 x 100 g-1 at 25, 70, and 115 min, respectively, after initiation of the study. The results suggest that isolated rat lungs perfused at rates that parallel normal rat cardiac output and ventilated at low peak inspiratory pressures provide a viable mechanism for evaluation of the pathophysiology of microvascular injury. PMID- 8366011 TI - Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. AB - The purpose of this study was to determine whether recombinant human growth hormone (GH) administration enhances muscle protein anabolism in experienced weight lifters. The fractional rate of skeletal muscle protein synthesis and the whole body rate of protein breakdown were determined during a constant intravenous infusion of [13C]leucine in 7 young (23 +/- 2 yr; 86.2 +/- 4.6 kg) healthy experienced male weight lifters before and at the end of 14 days of subcutaneous GH administration (40 microgram.kg-1 x day-1). GH administration increased fasting serum insulin-like growth factor-I (from 224 +/- 20 to 589 +/- 80 ng/ml, P = 0.002) but did not increase the fractional rate of muscle protein synthesis (from 0.034 +/- 0.004 to 0.034 +/- 0.002%/h) or reduce the rate of whole body protein breakdown (from 103 +/- 4 to 108 +/- 5 mumol.kg-1 x h-1). These findings suggest that short-term GH treatment does not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown, metabolic alterations that would promote muscle protein anabolism in experienced weight lifters attempting to further increase muscle mass. PMID- 8366012 TI - The detection and photography of vitamin A in fresh tissue by epi-fluorescence microscopy. PMID- 8366013 TI - Building a biomedical photography business: financial considerations. PMID- 8366014 TI - An inexpensive portable photographic background support system. PMID- 8366015 TI - The write stuff--an introduction to writing for publication. PMID- 8366016 TI - Environmental issues and the biophotographer. PMID- 8366017 TI - The use of cross-polarized illumination for patient photography. PMID- 8366018 TI - Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli. AB - Transcarboxylase from Propionibacterium shermanii is a complex biotin-containing enzyme composed of 30 polypeptides of three different types: a hexameric central 12S subunit to which 6 outer 5S subunits are attached through 12 1.3S biotinyl subunits. The enzyme catalyzes a two-step reaction in which methylmalonyl coenzyme A and pyruvate serve as substrates to form propionyl coenzyme A (propionyl-CoA) and oxalacetate, the 12S subunit specifically catalyzing one of the two reactions. We report here the cloning, sequencing, and expression of the 12S subunit. The gene was identified by matching amino acid sequences derived from isolated authentic 12S peptides with the deduced sequence of an open reading frame present in a cloned P. shermanii genomic fragment known to contain the gene encoding the 1.3S biotinyl subunit. The cloned 12S gene encodes a protein of 604 amino acids and of M(r) 65,545. The deduced sequence shows regions of extensive homology with the beta subunit of mammalian propionyl-CoA carboxylase as well as regions of homology with acetyl-CoA carboxylase from several species. Two genomic fragments were subcloned into pUC19 in an orientation such that the 12S open reading frame could be expressed from the lac promoter of the vector. Crude extracts prepared from these cells contained an immunoreactive band on Western blots (immunoblots) which comigrated with authentic 12S. The Escherichia coli expressed 12S was purified to apparent homogeneity by a three-step procedure and compared with authentic 12S from P. shermanii. Their quaternary structures were identical by electron microscopy, and the E. coli 12S preparation was fully active in the reactions catalyzed by this subunit. We conclude that we have cloned, sequenced, and expressed the 12S subunit which exists in a hexameric active form in E.coli. PMID- 8366019 TI - Bacteriophage Mu Mor protein requires sigma 70 to activate the Mu middle promoter. AB - Transcription during the bacteriophage Mu lytic cycle occurs in three phases: early, middle, and late. Middle transcription requires the early gene product Mor for its activation. Mor protein overproduction was accomplished by fusing the mor gene to an efficient phage T7 promoter and translation initiation region. A protein fraction highly enriched for Escherichia coli RNA polymerase (E sigma 70) from the Mor-overproducing strain was able to activate transcription from both the tac promoter (Ptac) and the Mu middle promoter (Pm) in vitro. Transcription initiation from Pm was Mor dependent, and the RNA 5' end was identical to that of in vivo RNA. Addition of anti-sigma 70 antibody to transcription reactions containing Ptac and Pm resulted in inhibition of transcription from both promoters; addition of purified sigma 70 restored transcription. These results indicate that Mor-dependent activation requires sigma 70 and therefore imply that Mor is not an alternate sigma factor. This conclusion was further substantiated by a reconstitution experiment with purified proteins in which all three components, Mor, sigma 70, and core RNA polymerase, were required for Pm dependent transcription in vitro. The sigma 70 dependence of Mor-specific transcription and the amino acid sequence similarity between Mor and C (an activator for Mu late transcription) both support the hypothesis that Mor functions mechanistically as an activator protein. PMID- 8366020 TI - Escherichia coli produces linoleic acid during late stationary phase. AB - Escherichia coli produces linoleic acid in the late stationary phase. This was the case whether the cultures were grown aerobically or anaerobically on a supplemented glucose-salts medium. The linoleic acid was detected by thin-layer chromatography and was measured as the methyl ester by gas chromatography. The linoleic acid methyl ester was identified by its mass spectrum. Lipids extracted from late-stationary-phase cells generated thiobarbituric acid-reactive carbonyl products when incubated with a free radical initiator. In contrast, extracts from log-phase or early-stationary-phase cells failed to do so, in accordance with the presence of polyunsaturated fatty acid only in the stationary-phase cells. PMID- 8366021 TI - Cloning and characterization of a gene whose product is a trans-activator of anthrax toxin synthesis. AB - The 184-kb Bacillus anthracis plasmid pXO1, which is required for virulence, contains three genes encoding the protein components of anthrax toxin, cya (edema factor gene), lef (lethal factor gene), and pag (protective antigen gene). Expression of the three proteins is induced by bicarbonate or serum. Using a pag lacZ transcriptional construct to measure pag promoter activity, we cloned in Bacillus subtilis a gene (atxA) whose product acts in trans to stimulate anthrax toxin expression. Deletion analysis located atxA on a 2.0-kb fragment between cya and pag. DNA sequencing identified one open reading frame encoding 476 amino acids with a predicted M(r) of 55,673, in good agreement with the value of 53 kDa obtained by in vitro transcription-translation analysis. The cloned atxA gene complemented previously characterized Tn917 insertion mutants UM23 tp29 and UM23 tp32 (J. M. Hornung and C. B. Thorne, Abstr. 91st Gen. Meet. Am. Soc. Microbiol. 1991, abstr. D-121, p. 98), which are deficient in synthesis of all three toxin proteins. These results demonstrate that the atxA product activates not only transcription of pag but also that of cya and lef. beta-Galactosidase synthesis from the pag-lacZ transcriptional fusion construct introduced into an insertion mutant (UM23 tp62) which does not require bicarbonate for toxin synthesis indicated that additional regulatory genes other than atxA play a role in the induction of anthrax toxin gene expression by bicarbonate. PMID- 8366022 TI - Subunit association in acetohydroxy acid synthase isozyme III. AB - Acetohydroxy acid synthase isozyme III (AHAS III) from Escherichia coli is composed of large and small subunits (encoded by the genes ilvI and ilvH) in an alpha 2 beta 2 structure. The large (61-kDa) subunit apparently contains the catalytic machinery of the enzyme, while the small (17-kDa) subunit is required for specific stabilization of the active conformation of the large subunit as well as for valine sensitivity. The interaction between subunits has been studied by using purified enzyme and extracts containing subcloned subunits. The association between large and small subunits is reversible, with a dissociation constant sufficiently high to have important experimental consequences: the activity of the enzyme shows a concentration dependence curve which is concave upward, and this dependence becomes linear upon the addition of excess large or small subunits. We estimate that at a concentration of 10(-7) M for each subunit (7 micrograms of enzyme ml-1), the large subunits are only half associated as the I2H2 active holoenzyme. This dissociation constant is high enough to cause underestimation of the activity of AHAS III in bacterial extracts. The true activity of this isozyme in extracts is observed in the presence of excess small subunits, which maintain the enzyme in its associated form. Reexamination of an E. coli K-12 ilvBN+ ilvIH+ strain grown in glucose indicates that AHAS III is the major isozyme expressed. As an excess of small subunits does not influence the apparent Ki for valine inhibition of the purified enzyme, it is likely that valine binds to and inhibits I2H2 rather than inducing dissociation. AHAS I and II seem to show a much lower tendency to dissociate than does AHAS III. PMID- 8366023 TI - Cloning, sequencing, and expression in Escherichia coli of the gene coding for phosphofructokinase in Lactobacillus bulgaricus. AB - A fragment of 1,185 bp containing the gene coding for phosphofructokinase (ATP:D fructose-6-phosphate-1-phosphotransferase; EC 2.7.1.11) in Lactobacillus bulgaricus has been cloned, sequenced, and expressed in Escherichia coli. The amino acid sequence of this enzyme was homologous to those of the ATP-dependent phosphofructokinases from E. coli, Thermus thermophilus, Spiroplasma citri, and Bacillus stearothermophilus, suggesting that these enzymes have closely related structures despite their different regulatory properties. The recombinant protein had the same structural and functional properties as did the original enzyme. The 3' end of the 1,185-bp fragment showed the presence of an open reading frame corresponding to the N-terminal amino acid sequence of the pyruvate kinase from L. bulgaricus. This gene organization, the same as that in S. citri (C. Chevalier, C. Saillard, and J. M. Bove, J. Bacteriol. 172:2693-2703, 1990) and B. stearothermophilus (D. Walker, W. N. Chia, and H. Muirhead, J. Mol. Biol. 228:265 276, 1992; H. Sakai and T. Ohta, Eur. J. Biochem. 311:851-859, 1993) but different from that in E. coli (H. W. Hellinga and P. R. Evans, Eur. J. Biochem. 149:363-373, 1985), indicated that the same transcription unit apparently contained the genes for phosphofructokinase and pyruvate kinase, the two key enzymes of glycolysis. The possibility that these genes could be transcribed at the same time suggested that in L. bulgaricus, the coordinated regulation of phosphofructokinase and pyruvate kinase occurs at the levels of both biosynthesis and enzymatic activity. PMID- 8366024 TI - Cysteine biosynthesis in Saccharomyces cerevisiae occurs through the transsulfuration pathway which has been built up by enzyme recruitment. AB - The transsulfuration pathways allow the interconversion of homocysteine and cysteine with the intermediary formation of cystathionine. The various organisms studied up to now incorporate reduced sulfur into a three- or a four-carbon chain and use differently the transsulfuration pathways to synthesize sulfur amino acids. In enteric bacteria, the synthesis of cysteine is the first step of organic sulfur metabolism and homocysteine is derived from cysteine. Fungi are capable of incorporating reduced sulfur into a four-carbon chain, and they possess two operating transsulfuration pathways. By contrast, synthesis of cysteine from homocysteine is the only existing transsulfuration pathway in mammals. In Saccharomyces cerevisiae, genetic, phenotypic, and enzymatic study of mutants has allowed us to demonstrate that homocysteine is the first sulfur amino acid to be synthesized and cysteine is derived only from homocysteine (H. Cherest and Y. Surdin-Kerjan, Genetics 130:51-58, 1992). We report here the cloning of genes STR4 and STR1, encoding cystathionine beta-synthase and cystathionine gamma lyase, respectively. The only phenotypic consequence of the inactivation of STR1 or STR4 is cysteine auxotrophy. The sequencing of gene STR4 has allowed us to compare all of the known sequences of transsulfuration enzymes and enzymes catalyzing the incorporation of reduced sulfur in carbon chains. These comparisons reveal a partition into two families based on sequence motifs. This partition mainly correlates with similarities in the catalytic mechanisms of these enzymes. PMID- 8366025 TI - Characterization of rcsB and rcsC from Escherichia coli O9:K30:H12 and examination of the role of the rcs regulatory system in expression of group I capsular polysaccharides. AB - In Escherichia coli K-12, RcsC and RcsB are thought to act as the sensor and effector components, respectively, of a two-component regulatory system which regulates expression of the slime polysaccharide colanic acid (V. Stout and S. Gottesman, J. Bacteriol. 172:659-669, 1990). Here, we report the cloning and DNA sequence of a 4.3-kb region containing rcsC and rcsB from E. coli O9:K30:H12. This strain does not produce colanic acid but does synthesize a K30 (group I) capsular polysaccharide. The rcsB gene from E. coli K30 (rcsBK30) is identical to the rcsB gene from E. coli K-12 (rcsBK-12). rcsCK30 has 16 nucleotide changes, resulting in six amino acid changes in the predicted protein. To examine the function of the rcs regulatory system in expression of the K30 capsular polysaccharide, chromosomal insertion mutations were constructed in E. coli O9:K30:H12 to independently inactivate rcsBK30 and the auxiliary positive regulator rcsAK30. Strains with these mutations maintained wild-type levels of K30 capsular polysaccharide expression and still produced a K30 capsule, indicating that the rcs system is not essential for expression of low levels of the group I capsular polysaccharide in lon+ E. coli K30. However, K30 synthesis is increased by introduction of a multicopy plasmid carrying rcsBK30. K30 polysaccharide expression is also markedly elevated in an rcsBK30-dependent fashion by a mutation in rcsCK30, suggesting that the rcs system is involved in high levels of synthesis. To determine whether the involvement of the rcs system in E. coli K30 expression is typical of group I (K antigen) capsules, multicopy rcsBK30 was introduced into 22 additional strains with structurally different group I capsules. All showed an increase in mucoid phenotype, and the polysaccharides produced in the presence and absence of multicopy rcsBK30 were examined. It is has been suggested that E. coli strains with group I capsules can be subdivided based on K antigen structure. For the first time, we show that strains with group I capsules can also be subdivided by the ability to produce colanic acid. Group IA contains capsular polysaccharides (including K30) with repeating-unit structures lacking amino sugars, and expression of group IA capsular polysaccharides is increased by multicopy rcsBK30. Group IB capsular polysaccharides all contain amino sugars. In group IB strains, multicopy rcsBK30 activates synthesis of colanic acid. PMID- 8366026 TI - Comparative analysis of flagellin sequences from Escherichia coli strains possessing serologically distinct flagellar filaments with a shared complex surface pattern. AB - Escherichia coli morphotype E flagellar filaments have a characteristic surface pattern of short-pitch loops when examined by electron microscopy. Seven of the 50 known E. coli H (flagellar antigen) serotypes (H1, H7, H12, H23, H45, H49, and H51) produce morphotype E filaments. Polymerase chain reaction was used to amplify flagellin structural (fliC) genes from E. coli strains producing morphotype E flagellar filaments and from strains with flagellar filaments representing other morphotypes. A single DNA fragment was obtained from each strain, and the size of the amplified DNA correlated with the molecular mass of the corresponding flagellin protein. This finding and hybridization data suggest that these bacteria are monophasic. fliC genes from three E. coli serotypes (H1, H7, and H12) possessing morphotype E flagellar filaments were sequenced in order to assess the contribution of conserved flagellin primary sequence to the characteristic filament architecture. The H1 and H12 fliC sequences were identical in length (1,788 bp), while the H7 fliC sequence was shorter (1,755 bp). The deduced molecular masses of the FliC proteins were 60,857 Da (H1), 59,722 Da (H7), and 60,978 Da (H12). The H1, H7, and H12 flagellins demonstrated 98 to 99% identity over the amino-terminal region (190 amino acid residues) and 89% (H7) to 99% (H1 and H12) identity in the carboxy-terminal region (100 amino acid residues). The complete primary amino acid sequences for H1 and H12 flagellins differed by only 10 amino acids, accounting for previously reported serological cross-reactions. However, the central region of H7 flagellin had only 38% identity with H1 and H12 flagellins. The characteristic morphology of morphotype E flagellar filaments is therefore not dependent on a highly conserved primary sequence within the exposed central region. Comparison of morphotype E E. coli flagellins with those from E. coli K-12, Serratia marcescens, and several Salmonella serovars supported the established concept of highly conserved terminal regions flanking a variable central region. PMID- 8366027 TI - Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b: cloning, sequencing, and expression of the tyrosinase gene mepA. AB - Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b (140 MDa). Transfer of this plasmid to GR4-cured derivatives or to Agrobacterium tumefaciens enables these bacteria to produce melanin. Sequence analysis of a 3.5-kb PstI fragment of plasmid pRmeGR4b has revealed the presence of a open reading frame 1,481-bp that codes for a protein whose sequence shows strong homology to two conserved regions involved in copper binding in tyrosinases and hemocyanins. In vitro-coupled transcription-translation experiments showed that this open reading frame codes for a 55-kDa polypeptide. Melanin production in GR4 is not under the control of the RpoN-NifA regulatory system, unlike that in R. leguminosarum bv. phaseoli 8002. The GR4 tyrosinase gene could be expressed in Escherichia coli under the control of the lacZ promoter. For avoiding confusion with mel genes (for melibiose), a change of the name of the previously reported mel genes of R. leguminosarum bv. phaseoli and other organisms to mep genes (for melanin production) is proposed. PMID- 8366028 TI - A rapid method for cloning mutagenic DNA repair genes: isolation of umu complementing genes from multidrug resistance plasmids R391, R446b, and R471a. AB - Genetic and physiological experiments have demonstrated that the products of the umu-like operon are directly required for mutagenic DNA repair in enterobacteria. To date, five such operons have been cloned and studied at the molecular level. Given the apparent wide occurrence of these mutagenic DNA repair genes in enterobacteria, it seems likely that related genes will be identified in other bacterial species and perhaps even in higher organisms. We are interested in identifying such genes. However, standard methods based on either DNA or protein cross-hybridization are laborious and, given the overall homology between previously identified members of this family (41 to 83% at the protein level), would probably have limited success. To facilitate the rapid identification of more diverse umu-like genes, we have constructed two Escherichia coli strains that allow us to identify umu-like genes after phenotypic complementation assays. With these two strains, we have cloned novel umu-like genes from three R plasmids, the IncJ plasmid R391 and two IncL/M plasmids, R446b and R471a. PMID- 8366029 TI - Genetic analysis of microcin H47 antibiotic system. AB - The microcin H47 genetic determinants span a DNA region of ca. 10 kb and represent the first description of an enterobacterial antibiotic system located in the chromosome of the producing strain. Transcriptional and translational fusions to lacZ showed a complex transcriptional organization of the microcin H47 system. Complementation tests identified six genes that are necessary for the production of the antibiotic; the products of two of them are involved in the export of microcin to the extracellular medium. The immunity determinant was located in an 0.8-kb DNA fragment. There is a putative "silent region" of ca. 3 kb inside the system that could not be clearly related to any antibiotic function. Protein products were identified and assigned to three production genes and also to a gene from the silent region. PMID- 8366030 TI - Characteristics and osmoregulatory roles of uptake systems for proline and glycine betaine in Lactococcus lactis. AB - Lactococcus lactis subsp. lactis ML3 contains high pools of proline or betaine when grown under conditions of high osmotic strength. These pools are created by specific transport systems. A high-affinity uptake system for glycine betaine (betaine) with a Km of 1.5 microM is expressed constitutively. The activity of this system is not stimulated by high osmolarities of the growth or assay medium but varies strongly with the medium pH. A low-affinity proline uptake system (Km, > 5 mM) is expressed at high levels only in chemically defined medium (CDM) with high osmolarity. This transport system is also stimulated by high osmolarity. The expression of this proline uptake system is repressed in rich broth with low or high osmolarity and in CDM with low osmolarity. The accumulated proline can be exchanged for betaine. Proline uptake is also effectively inhibited by betaine (Ki of between 50 and 100 microM). The proline transport system therefore probably also transports betaine. The inhibition of proline transport by betaine results in low proline pools in cells grown in high-osmotic-strength, betaine containing CDM. The energy and pH dependency and the influence of ionophores on the activity of both transport systems suggest that these systems are not proton motive force driven. At low osmolarities, proline uptake is low but significant. This low proline uptake is also inhibited by betaine, although to a lesser extent than in cells grown in high-osmotic-strength CDM. These data indicate that proline uptake in L. lactis is enzyme mediated and is not dependent on passive diffusion, as was previously believed. PMID- 8366031 TI - Enhancer-like activity of A1gR1-binding site in alginate gene activation: positional, orientational, and sequence specificity. AB - Significant activation of promoters of alginate genes such as algD or algC occurs in mucoid Pseudomonas aeruginosa during its proliferation in the lungs of cystic fibrosis patients. These promoters have been shown to be responsive to environmental signals such as high osmolarity. The signaling is mediated by a so called two-component signal transduction system, in which a soluble protein, AlgR2, undergoes autophosphorylation and transfers the phosphate to a DNA-binding response regulator protein, AlgR1. The phosphorylated form of AlgR1 has a high affinity for binding at upstream sequences of both the algC and algD promoters. Two AlgR1-binding sites (ABS) have been reported upstream of the algC gene. One of the two ABSs (algC-ABS1, located at -94 to -81) is critical for the algC activation process, while the second ABS (algC-ABS2, located at +161 to +174) is only weakly active. We now report the presence of a third ABS within the structural gene of algC, and this ABS (algC-ABS3) is also important for algC promoter activation. algC-ABS1 can be replaced functionally by algC-ABS2, algD ABS1, or algD-ABS2 and somewhat weakly by algD-ABS3. Introduction of a half integral turn in the DNA helix between the algC site of transcription initiation and algC-ABS1 allowed only slight reduction of promoter activity, suggesting that the binding site could be appreciably functional even when present in the opposite face of the helix. Activation of the algC promoter is independent of the relative location (upstream or downstream of the mRNA start site), the number of copies, or the orientation of algC-ABS1, suggesting that it behaves like a eukaryotic enhancer element in promoting transcription from the algC promoter. PMID- 8366032 TI - Methionine-mediated lethality in yeast cells at elevated temperature. AB - Saccharomyces cerevisiae cells grown at 30 degrees C in minimal medium containing methionine lose viability upon transfer to 45 degrees C, whereas cells grown in the absence of methionine survive. Cellular levels of two intermediates in the sulfate assimilation pathway, adenosine 5'-phosphosulfate (APS) and adenosine 5' phosphosulfate 3'-phosphate, are increased by a posttranslational mechanism after sudden elevation of temperature in yeast cultures grown in the absence of methionine. Yeast cells unable to synthesize APS because of repression by methionine or mutation of the MET3 gene do not survive the temperature shift. Thus, methionine-mediated lethality at elevated temperature is linked to the inability to synthesize APS. The results demonstrate that APS plays an important role in thermotolerance. PMID- 8366033 TI - Phenotype conversion in Pseudomonas solanacearum due to spontaneous inactivation of PhcA, a putative LysR transcriptional regulator. AB - Phenotype conversion (PC) in Pseudomonas solanacearum is the coordinated change in production of extracellular polysaccharide and a variety of extracellular proteins, some of which contribute to virulence. Although PC is normally spontaneous, it is mimicked by transposon inactivation of the phcA locus (S. M. Brumbley and T. P. Denny, J. Bacteriol. 172:5677-5685, 1990). The DNA sequence of a 1.8-kb region from strain AW1 that contains phcA revealed one open reading frame that should encode a polypeptide of 38.6 kDa. The PhcA protein produced in Escherichia coli by using a T7 RNA polymerase expression system was of the predicted size. The deduced amino acid sequence of PhcA is similar to that of some members of the LysR transcriptional activator gene family, especially in the amino terminus, where a putative helix-turn-helix DNA-binding motif was identified. An analogous allele (phcA1) was cloned from the spontaneous PC mutant strain AW1-PC and found to be nonfunctional in complementation studies. When phcA1 was expressed in E. coli, the PhcA1 protein was 35.5 kDa, 3 kDa smaller than PhcA. Sequence analysis of phcA1 and chimeric constructs of phcA and phcA1 confirmed that PhcA1 is truncated by a 2-bp insertion 147 nucleotides upstream of the carboxyl terminus of PhcA. Southern blot analysis of 10 additional independently isolated PC mutants of strain AW1 revealed that two strains have larger insertions (0.2 and 1.0 kb) within phcA. These results suggest that phcA encodes a DNA-binding protein that regulates the transcription of one or more of the genes involved in P. solanacearum virulence and that spontaneous PC can be attributed to one of several different insertions within this locus. PMID- 8366034 TI - High-molecular-weight protein 2 of Yersinia enterocolitica is homologous to AngR of Vibrio anguillarum and belongs to a family of proteins involved in nonribosomal peptide synthesis. AB - The iron-regulated irp2 gene is specific for the highly pathogenic Yersinia species and encodes high-molecular-weight protein 2 (HMWP2). Despite the established correlation between the presence of HMWP2 and virulence, the role of this protein is still unknown. To gain insight into the function of HMWP2, the entire coding sequence and the promoter of irp2 were sequenced. Two putative -35 and -10 promoter sequences were identified upstream of a large open reading frame, and two potential Fur-binding sites were found overlapping the second -35 box. The large open reading frame is composed of 6,126 nucleotides and may encode a protein of 2,035 amino acids (ca. 228 kDa) with a pI of 5.81. A signal sequence was not present at the N terminus of the protein. Despite the existence of 30 cysteine residues, carboxymethylation prevented the formation of most if not all disulfide bonds that otherwise occurred when the cells were sonicated. The protein was composed of three main domains: a central region of ca. 850 residues, bordered on each side by a repeat of 550 residues. A high degree of identity (44.5%) was found between HMWP2 and the protein AngR of Vibrio anguillarum. The central part of HMWP2 (after removal of a loop of 337 residues) also displayed significant homology with proteins belonging to the superfamily of adenylate forming enzymes and, like them, possessed a putative ATP-binding motif that is also present in AngR. In addition, HMWP2 shared with the group of antibiotic and enterochelin synthetases a potential amino acid-binding site. Six consensus sequences defining the superfamily and four defining the family of synthetases were derived from the multiple alignment of the 30 sequences of proteins or repeated domains. A phylogenetic tree that was constructed showed that HMWP2 and AngR are in a family composed of Lys2, EntF, and the tyrocidine, gramicidin, and Beta-lactam synthetases. This finding suggests that HMWP2 may participate in the nonribosomal synthesis of small biologically active peptides. PMID- 8366035 TI - Degradation of individual chromosomes in recA mutants of Escherichia coli. AB - Rapidly growing wild-type Escherichia coli cells contain two, four, or eight fully replicated chromosomes after treatment with rifampin, reflecting that all replication origins are initiated simultaneously. Cells with defects in the timing of the initiation of replication may contain three, five, six, or seven fully replicated chromosomes after such treatment. This phenotype, termed the asynchrony phenotype, is also seen in recombination-deficient recA mutants. It is shown here that for recA strains, the phenotype can be explained by a selective and complete degradation of individual chromosomes. The selective degradation is largely recD dependent and is thus carried out by the RecBCD exonuclease. PMID- 8366036 TI - Cloning of a chromosomal gene required for phage infection of Lactococcus lactis subsp. lactis C2. AB - A phage-resistant mutant with a defect in a membrane component required for phage infections in Lactococcus lactis subsp. lactis C2 was transformed with a chromosomal library of the wild-type, phage-sensitive strain. Of the 4,200 transformants screened for phage sensitivity, three were positively identified as phage sensitive. A cause-and-effect relationship between the cloned chromosomal fragments and the phage-sensitive phenotype was established on the basis of the following two criteria: (i) the frequency of loss of the cloned fragments in the absence of antibiotic selection pressure correlated with the frequency of loss of phage sensitivity; and (ii) phage sensitivity was transferred to 100% of recipient, phage-resistant cells transformed with the cloned fragment. The cloned chromosomal DNA from the three independent isolates was physically mapped with restriction endonucleases. The sizes of the cloned fragments were 9.6, 11.8, and 9.5 kb. Each fragment contained an identical stretch of DNA common to all three, which was 9.4 kb. The gene that conferred phage sensitivity was localized by subcloning to a 4.5-kb region. Further subcloning indicated that a single EcoRI site within the 4.5-kb region must lie within the gene or its promoter. The required 4.5-kb region was sequenced and found to code for one partial and two complete open reading frames. The gene required for complementation was functionally mapped by Tn5 mutagenesis and localized to one of the two complete open reading frames, which was designated pip (an acronym for phage infection protein). pip is 2,703 bases in length. Potential promoters start 206 and 212 bases upstream of the open reading frame. A ribosome binding site and a seven base spacer precede the GTG (Val) translation initiation codon. The amino acid sequence deduced from the gene has 901 residues and an M(r) of 99,426. Hydropathy analysis revealed four to six potential membrane-spanning regions, one near the amino terminus and the others at the extreme carboxyl terminus. The amino terminus has characteristics of a signal sequence. The putative protein would have a 650-residue, central polar domain. PMID- 8366037 TI - Glucose uptake and catabolite repression in dominant HTR1 mutants of Saccharomyces cerevisiae. AB - Growth and carbon metabolism in triosephosphate isomerase (delta tpi1) mutants of Saccharomyces cerevisiae are severely inhibited by glucose. By using this feature, we selected for secondary site revertants on glucose. We defined five complementation groups, some of which have previously been identified as glucose repression mutants. The predominant mutant type, HTR1 (hexose transport regulation), is dominant and causes various glucose-specific metabolic and regulatory defects in TPI1 wild-type cells. HTR1 mutants are deficient in high affinity glucose uptake and have reduced low-affinity transport. Transcription of various known glucose transporter genes (HXT1, HXT3, and HXT4) was defective in HTR1 mutants, leading us to suggest that HTR mutations affect a negative factor of HXT gene expression. By contrast, transcript levels for SNF3, which encodes a component of high-affinity glucose uptake, were unaffected. We presume that HTR1 mutations affect a negative factor of HXT gene expression. Multicopy expression of HXT genes or parts of their regulatory sequences suppresses the metabolic defects of HTR1 mutants but not their derepressed phenotype at high glucose concentrations. This suggests that the glucose repression defect is not a direct result of the metabolically relevant defect in glucose transport. Alternatively, some unidentified regulatory components of the glucose transport system may be involved in the generation or transmission of signals for glucose repression. PMID- 8366038 TI - Transfer functions of the conjugative integrating element pSAM2 from Streptomyces ambofaciens: characterization of a kil-kor system associated with transfer. AB - pSAM2 is an 11-kb integrating element from Streptomyces ambofaciens. During matings, pSAM2 can be transferred at high frequency, forming pocks, which are zones of growth inhibition of the recipient strain. The nucleotide sequences of the regions involved in pSAM2 transfer, pock formation, and maintenance have been determined. Seven putative open reading frames with the codon usage typical of Streptomyces genes have been identified: traSA (306 amino acids [aa]), orf84 (84 aa), spdA (224 aa), spdB (58 aa), spdC (51 aa), spdD (104 aa), and korSA (259 aa). traSA is essential for pSAM2 intermycelial transfer and pock formation. It could encode a protein with similarities to the major transfer protein, Tra, of pIJ101. TraSA protein contains a possible nucleotide-binding sequence and a transmembrane segment. spdA, spdB, spdC, and spdD influence pock size and transfer efficiency and may be required for intramycelial transfer. A kil-kor system similar to that of pIJ101 is associated with pSAM2 transfer: the korSA (kil-override) gene product could control the expression of the traSA gene, which has lethal effects when unregulated (Kil phenotype). The KorSA protein resembles KorA of pIJ101 and repressor proteins belonging to the GntR family. Thus, the integrating element pSAM2 possesses for transfer general features of nonintegrating Streptomyces plasmids: different genes are involved in the different steps of the intermycelial and intramycelial transfer, and a kil-kor system is associated with transfer. However, some differences in the functional properties, organization, and sizes of the transfer genes compared with those of other Streptomyces plasmids have been found. PMID- 8366039 TI - New method for gene disruption in Salmonella typhimurium: construction and characterization of an ada-deletion derivative of Salmonella typhimurium TA1535. AB - A new method for gene disruption in Salmonella typhimurium was developed. The key steps of this method are to produce restriction fragments with compatible ends, preligate to produce concatemers, and then transform by electrotransformation. We developed and used this method to construct a mutant of S. typhimurium TA1535 in which the resident ada-like (adaST) gene was replaced with a kanamycin resistance gene to produce an adaST-deletion mutant derivative. The S. typhimurium adaST deletion strain did not exhibit a higher level of mutability upon treatment with N-methyl-N'-nitro-N-nitrosoguanidine than did its wild-type parent strain. However, it did exhibit a higher sensitivity with respect to killing by N-methyl N'-nitro-N-nitrosoguanidine. The ability of AdaST to function as a transcriptional activator is discussed. PMID- 8366040 TI - Cloning, primary structure, and regulation of the HIS7 gene encoding a bifunctional glutamine amidotransferase: cyclase from Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae HIS7 gene was cloned by its location immediately downstream of the previously isolated and characterized ARO4 gene. The two genes have the same orientation with a distance of only 416 bp between the two open reading frames. The yeast HIS7 gene represents the first isolated eukaryotic gene encoding the enzymatic activities which catalyze the fifth and sixth step in histidine biosynthesis. The open reading frame of the HIS7 gene has a length of 1,656 bp resulting in a gene product of 552 amino acids with a calculated molecular weight of 61,082. Two findings implicate a bifunctional nature of the HIS7 gene product. First, the N-terminal and C-terminal segments of the deduced HIS7 amino acid sequence show significant homology to prokaryotic monofunctional glutamine amidotransferases and cyclases, respectively, involved in histidine biosynthesis. Second, the yeast HIS7 gene is able to suppress His auxotrophy of corresponding Escherichia coli hisH and hisF mutants. HIS7 gene expression is regulated by the general control system of amino acid biosynthesis. GCN4 dependent and GCN4-independent (basal) transcription use different initiator elements in the HIS7 promoter. PMID- 8366041 TI - The Candida albicans plasma membrane and H(+)-ATPase during yeast growth and germ tube formation. AB - PMA1 expression, plasma membrane H(+)-ATPase enzyme kinetics, and the distribution of the ATPase have been studied in carbon-starved Candida albicans induced with glucose for yeast growth at pH 4.5 and for germ tube formation at pH 6.7. PMA1 expression parallels expression of the constitutive ADE2 gene, increasing up to sixfold during yeast growth and twofold during germ tube formation. Starved cells contain about half the concentration of plasma membrane ATPase of growing cells. The amount of plasma membrane ATPase is normalized prior to either budding or germ tube emergence by the insertion of additional ATPase molecules, while ATPase antigen appears uniformly distributed over the entire plasma membrane surface during both growth phases. Glucose addition rapidly activates the ATPase twofold regardless of the pH of induction. The turnover of substrate molecules per second by the enzyme in membranes from budding cells quickly declines, but the enzyme from germ tube-forming cells maintains its turnover of substrate molecules per second and a higher affinity for Mg-ATP. The plasma membrane ATPase of C. albicans is therefore regulated at several levels; by glucose metabolism/starvation-related factors acting on gene expression, by signals generated through glucose metabolism/starvation which are thought to covalently modify the carboxyl-terminal domain of the enzyme, and possibly by additional signals which may be specific to germ tube formation. The extended period of intracellular alkalinization associated with germ tube formation may result from regulation of proton-pumping ATPase activity coupled with higher ratios of cell surface to effective cytosolic volume. PMID- 8366042 TI - Genetic analysis of the agrocinopine catabolic region of Agrobacterium tumefaciens Ti plasmid pTiC58, which encodes genes required for opine and agrocin 84 transport. AB - The acc region, subcloned from pTiC58 of classical nopaline and agrocinopine A and B Agrobacterium tumefaciens C58, allowed agrobacteria to grow using agrocinopine B as the sole source of carbon and energy. acc is approximately 6 kb in size. It consists of at least five genes, accA through accE, as defined by complementation analysis using subcloned fragments and transposon insertion mutations of acc carried on different plasmids within the same cell. All five regions are required for agrocin 84 sensitivity, and at least four are required for agrocinopine and agrocin 84 uptake. The complementation results are consistent with the hypothesis that each of the five regions is separately transcribed. Maxicell experiments showed that the first of these genes, accA, encodes a 60-kDa protein. Analysis of osmotic shock fractions showed this protein to be located in the periplasm. The DNA sequence of the accA region revealed an open reading frame encoding a predicted polypeptide of 59,147 Da. The amino acid sequence encoded by this open reading frame is similar to the periplasmic binding proteins OppA and DppA of Escherichia coli and Salmonella typhimurium and OppA of Bacillus subtilis. PMID- 8366043 TI - Isoleucine synthesis in Corynebacterium glutamicum: molecular analysis of the ilvB-ilvN-ilvC operon. AB - Acetohydroxy acid synthase (AHAS) and isomeroreductase (IR) catalyze subsequent reactions in the flux of metabolites towards isoleucine, valine, leucine, and pantothenate. A 4,705-bp DNA fragment from Corynebacterium glutamicum known to code for AHAS and IR was sequenced and analyzed by Northern (RNA blot) analysis. As in other bacteria, the AHAS of this gram-positive organism is encoded by two genes, ilvB and ilvN. Gene disruption verified that these genes encode the single AHAS activity in C. glutamicum. The start of ilvB was determined by amino terminal sequencing of a fusion peptide. By Northern analysis of the ilvBNC cluster, three in vivo transcripts of 3.9, 2.3, and 1.1 kb were identified, corresponding to ilvBNC, ilvNC, and ilvC messages, respectively. The ilvC transcript (encoding IR) was by far the most abundant one. With a clone from which the ilvB upstream regions had been deleted, only the ilvNC and ilvC transcripts were synthesized, and with a clone from which the ilvN upstream regions had been deleted, only the smallest ilvC transcript was formed. It is therefore concluded that in the ilv operon of C. glutamicum, three promoters are active. The amounts of the ilvBNC and ilvNC transcripts increased in response to the addition of alpha-ketobutyrate to the growth medium. This was correlated to an increase in specific AHAS activity, whereas IR activity was not increased because of the relatively large amount of the ilvC transcript present under all conditions assayed. Therefore, the steady-state level of the ilvBNC and ilvNC messages contributes significantly to the total activity of the single AHAS. The ilvC transcript of this operon, however, is regulated independently and present in a large excess, which is in accord with the constant IR activities determined. PMID- 8366044 TI - Identification, isolation, and overexpression of the gene encoding the psi subunit of DNA polymerase III holoenzyme. AB - The gene encoding the psi subunit of DNA polymerase III holoenzyme, holD, was identified and isolated by an approach in which peptide sequence data were used to obtain a DNA hybridization probe. The gene, which maps to 99.3 centisomes, was sequenced and found to be identical to a previously uncharacterized open reading frame that overlaps the 5' end of rimI by 29 bases, contains 411 bp, and is predicted to encode a protein of 15,174 Da. When expressed in a plasmid that also expressed holC, holD directed expression of the psi subunit to about 3% of total soluble protein. PMID- 8366045 TI - Mutation in the plasmid pUB110 Rep protein affects termination of rolling circle replication. AB - We isolated a mutant of plasmid pUB110 that has the following properties in Bacillus subtilis: (i) it is toxic for recA and add cells, particularly at elevated temperature; (ii) it has a copy number threefold higher than that of the parental plasmid, and the extra copies are present as multimers; and (iii) it can efficiently complement replication of a cmp- satellite plasmid, despite being cmp+. All these properties are due to a single change in the plasmid replication protein, i.e., Gly at position 148 to Glu. These properties of the mutant Rep protein reflect a diminished ability to terminate rolling circle replication. We propose that the Rep protein may have a diminished affinity for the plasmid origin; alternatively, it may be impaired for recognition of the plasmid conformations which distinguish initiation and termination. PMID- 8366047 TI - Escherichia coli rpiA gene encoding ribose phosphate isomerase A. AB - The rpiA gene encoding ribose phosphate isomerase A was cloned from phage 1A2(471) of the Kohara gene library. Subcloning, restriction, and complementation analyses revealed an 1,800-bp SspI-generated DNA fragment that contained the entire control and coding sequences. This DNA fragment was sequenced and shown to harbor an open reading frame of 219 codons, sufficient to encode a polypeptide with an M(r) of 22,845. The synthesis of the rpiA-encoded polypeptide was detected by analysis of minicells, which established the subunit M(r) as 27,000. The assignment of the correct reading frame was confirmed by amino-terminal analysis of partially purified ribose phosphate isomerase A. Our data indicate that the enzyme is composed of two identical subunits. The 5' end of the rpiA specified transcript was analyzed by primer extension, which revealed a well conserved -10 region 34 bp upstream of the presumed translation start codon. Analysis of the 3' end of the transcript by S1 nuclease mapping showed that transcription termination occurred within an adenylate-rich sequence following a guanylate-cytidylate-rich stem-loop structure resembling a rho factor-independent transcription terminator. Host strains harboring the rpiA gene in a multicopy plasmid contained up to 42-fold as much ribose phosphate isomerase A activity as the haploid strain. PMID- 8366048 TI - Molecular and phenotypic characterization of promoter-proximal mutations in the spoIIA locus of Bacillus subtilis. AB - Eight mutations lying within the promoter-proximal one-fifth of the spoIIA locus of Bacillus subtilis were studied. Two of these mutations (spoIIAA42 and spoIIAA69) were previously characterized at the DNA level, five more (spo-562, spo-565, spo-567, spo-568, and spo-569) were isolated in our laboratory several years ago but not fully characterized, and the eight (an in-frame deletion confined to spoIIAA, the first gene in the spoIIA operon) was constructed for this study. DNA sequencing showed that spo-569 was a transitions in the -35 region of the spoIIA promoter; the remaining point mutations were all G:C to A:T transitions in spoIIAA, with spo-565 having two transitions, one of which was identical to that in spo-562. All the spoIIAA mutations except spo-562 led to the replacement of Gly residues. The incidence of sporulation, the rate of synthesis of sporulation-associated alkaline phosphatase, and the rate of expression of the forespore-specific genes gpr and spoIIIG were determined for isogenic strains carrying the eight mutations. All the mutations except spoIIAA42 and spo-569 (which were slightly leaky) made the strains asporogenous, and all except spo-562 and spo-569 abolished the synthesis of alkaline phosphatase and the expression of gpr and spoIIIG. spo-562 allowed alkaline phosphatase synthesis and gpr and spoIIIG expression to occur at about 15% of the wild-type rates but with normal kinetics. spo-59 allowed appreciable gpr and spoIIIG expression during exponential growth; we attribute this expression to transcription by RNA polymerase containing sigma G and suggest that a spo-569 strain makes insufficient SpoIIAB to inhibit sigma G in growing cells. PMID- 8366046 TI - Cloning, sequencing, expression, and regulation of the structural gene for the copper/topa quinone-containing methylamine oxidase from Arthrobacter strain P1, a gram-positive facultative methylotroph. AB - Deoxyoligonucleotides corresponding to amino acid sequences of methylamine oxidase and polyclonal anti-methylamine oxidase antibodies were used to probe Arthrobacter strain P1 plasmid and chromosomal DNA libraries. Two open reading frames, maoxI and maoxII, which are greater than 99% homologous, were cloned from the chromosomal library. The deduced amino acid sequences of the coding regions are identical except for two residues near the C termini. On the other hand, the 5'- and 3'-flanking regions of maoxI and maoxII are quite different. While either gene could code for methylamine oxidase, the dissimilarity in the 5'-flanking regions indicates that the genes are differently regulated. It was determined that maoxII alone encodes methylamine oxidase. The tyrosyl residue which is converted to topa quinone in the mature enzyme was located by comparison with amino acid sequences at the cofactor sites in other copper/topa quinone containing amine oxidase. Transcriptional start sites and possible regulatory elements were identified in the 5' region of maoxI and maoxII, and stem-loop structures were found in the 3'-flanking regions. High levels of methylamine oxidase are produced when Arthrobacter strain P1 is grown on methylamine alone or on glucose plus methylamine, but growth on LB medium plus methylamine resulted in very low production of the enzyme. Expression of maoxII from its own promoter in Escherichia coli grown on glucose or LB medium with or without methylamine gave the same level of production of methylamine oxidase. PMID- 8366049 TI - Escherichia coli mutants lacking NADH dehydrogenase I have a competitive disadvantage in stationary phase. AB - We have previously characterized mutant strains of Escherichia coli that are able to take over stationary-phase cultures. Here we describe two insertion mutations that prevent such strains from expressing this phenotype. Both insertions were mapped to min 51, and sequence analysis revealed that both mutated genes encode proteins homologous to subunits of mitochondrial NADH dehydrogenase I. Crude extracts prepared from both mutant strains were able to oxidize NADH but lacked the enzymatic activity needed to oxidize deamino-NADH, a substrate specific for NADH dehydrogenase I. This is the first identification of genes encoding subunits of NADH dehydrogenase I in E. coli. The significance of the inability of these mutant strains to compete in stationary-phase cultures is discussed. PMID- 8366050 TI - A cryptic promoter in the O(R) region of bacteriophage lambda. AB - A cryptic promoter, designated P alpha, initiates transcription within the O(R) region of bacteriophage lambda. Transcription from P alpha proceeds in the direction of the cI repressor gene from sites 46 and 48 bp preceding the PRM transcription start site. P alpha is likely to compete with both PR and PRM for formation of open complexes, since it is only active when PR is mutated and can be suppressed by mutations that increase PRM activity. In addition, transcription initiation at P alpha is blocked by lambda repressor. Kinetic analysis of relative abundance of the products of in vitro transcription indicated that P alpha was approximately 1/3 as strong as PRM. However, a P alpha mutation had little effect on KBkf (the association rate constant) for PRM. These observations can be explained by the finding that open complexes formed at P alpha are relatively unstable (half-life = 20 to 25 min). Dissociation of RNA polymerase from P alpha allows additional open complexes to form at PR or PRM, and thus the apparent strength of P alpha decreases with increasing preincubation times. PMID- 8366051 TI - Maltose and maltotriose can be formed endogenously in Escherichia coli from glucose and glucose-1-phosphate independently of enzymes of the maltose system. AB - The maltose system in Escherichia coli consists of cell envelope-associated proteins and enzymes that catalyze the uptake and utilization of maltose and alpha,1-4-linked maltodextrins. The presence of these sugars in the growth medium induces the maltose system (exogenous induction), even though only maltotriose has been identified in vitro as an inducer (O. Raibaud and E. Richet, J. Bacteriol., 169:3059-3061, 1987). Induction is dependent on MalT, the positive regulator protein of the system. In the presence of exogenous glucose, the maltose system is normally repressed because of catabolite repression and inducer exclusion brought about by the phosphotransferase-mediated vectorial phosphorylation of glucose. In contrast, the increase of free, unphosphorylated glucose in the cell induces the maltose system. A ptsG ptsM glk mutant which cannot grow on glucose can accumulate [14C]glucose via galactose permeases. In this strain, internal glucose is polymerized to maltose, maltotriose, and maltodextrins in which only the reducing glucose residue is labeled. This polymerization does not require maltose enzymes, since it still occurs in malT mutants. Formation of maltodextrins from external glucose as well as induction of the maltose system is absent in a mutant lacking phosphoglucomutase, and induction by external glucose could be regained by the addition of glucose-1 phosphate entering the cells via a constitutive glucose phosphate transport system. malQ mutants, which lack amylomaltase, are constitutive for the expression of the maltose genes. This constitutive nature is due to the formation of maltose and maltodextrins from the degradation of glycogen. PMID- 8366053 TI - Characterization of a membrane-associated ATPase from Methanococcus voltae, a methanogenic member of the Archaea. AB - A membrane-associated ATPase with an M(r) of approximately 510,000 and containing subunits with M(r)s of 80,000 (alpha), 55,000 (beta), and 25,000 (gamma) was isolated from the methanogen Methanococcus voltae. Enzymatic activity was not affected by vanadate or azide, inhibitors of P- and F1-ATPase, respectively, but was inhibited by nitrate and bafilomycin A1, inhibitors of V1-type ATPases. Since dicyclohexylcarbodiimide inhibited the enzyme when it was present in membranes but not after the ATPase was solubilized, we suggest the presence of membrane associated component analogous to the F0 and V0 components of both F-type and V type ATPases. N-terminal amino acid sequence analysis of the alpha subunit showed a higher similarity to ATPases of the V-type family than to those of the F-type family. PMID- 8366052 TI - The major iron-containing protein of Legionella pneumophila is an aconitase homologous with the human iron-responsive element-binding protein. AB - Legionella pneumophila has high iron requirements, and its intracellular growth in human monocytes is dependent on the availability of intracellular iron. To learn more about iron metabolism in L. pneumophila, we have undertaken an analysis of the iron proteins of the bacterium. We first developed an assay to identify proteins by 59Fe labelling and nondenaturing polyacrylamide gel electrophoresis. The assay revealed seven iron proteins (IPs) with apparent molecular weights of 500, 450, 250, 210, 150, 130, and 85. IP150 comigrates with superoxide dismutase activity and is probably the Fe-superoxide dismutase of L. pneumophila. IP210 is the major iron-containing protein (MICP). To identify and characterize MICP, we purified the protein and cloned and sequenced its gene. MICP is a monomeric protein containing 891 amino acids, and it has a calculated molecular mass of 98,147 Da. Analysis of the sequence revealed that MICP has two interesting homologies. First, MICP is highly homologous with the human iron responsive element-binding protein, consistent with the hypothesis that this critical iron-regulatory molecule of humans has a prokaryotic ancestor. Second, MICP is highly homologous with the Escherichia coli aconitase and to a lesser extent with porcine heart mitochondrial aconitase. Consistent with this, we found that MICP exhibits aconitase activity. In contrast to other aconitases, MICP has a single amino acid change of a potentially deleterious type at a site thought to be critical for substrate binding and enzymatic activity. However, the specific activity of MICP is roughly comparable to that of other aconitases, suggesting that the mutation has at most a mild effect on the aconitase activity of MICP. The abundance of MICP in L. pneumophila suggests either that L. pneumophila requires high aconitase and perhaps tricarboxylic acid cycle activity or that the bacterium requires large amounts of this protein to serve an additional role in bacterial physiology. A need for large amounts of MICP, which contains four Fe atoms per molecule when fully loaded, could at least partly explain L. pneumophila's high metabolic requirement for iron. PMID- 8366054 TI - Isolation of a Candida albicans DNA sequence conferring adhesion and aggregation on Saccharomyces cerevisiae. AB - Candida albicans is an opportunistic pathogen which may give rise to superficial and systemic infections. In the present study, C. albicans adhesion was studied by expression of C. albicans DNA sequences encoding adhesion functions in a nonadherent strain of Saccharomyces cerevisiae. Adherent transformant cells of S. cerevisiae harbouring a C. albicans genomic library cloned in a yeast-Escherichia coli shuttle vector were selected by using tissue culture-treated polystyrene as the attachment substratum. One transformant exhibited enhanced adhesion to treated and untreated polystyrene as well as autoaggregation, unlike control cells bearing the vector alone. Analysis of this clone revealed an insert of ca. 4.5 kb from C. albicans. Curing of the plasmid resulted in loss of adhesion and autoaggregation properties. A subclone bearing a reduced insert of 3.3 kb retained the ability to autoaggregate, to bind to treated and untreated polystyrene, and to adhere to buccal epithelial cells, unlike appropriate controls. Further subcloning of the insert to 2.7- and 1.9-kb fragments resulted in incremental decreases in adhesion and autoaggregation, whereas smaller fragments did not confer these properties. Hybridization of the 2.7-kb segment with C. albicans and S. cerevisiae DNA confirmed its origin as a single-copy sequence in the C. albicans genome as well as the absence of a homologous sequence in the genome of S. cerevisiae. The data suggest that the adhesion and aggregation phenomena of the transformant cells are related to expression of a C. albicans surface antigen encoded by the cloned DNA fragment. PMID- 8366055 TI - Chloramphenicol acetyltransferase, a cytoplasmic protein is incompatible for export from Bacillus subtilis. AB - Bacillus subtilis cells expressing a hybrid protein (Lvsss-Cat) consisting of the B. amyloliquefaciens levansucrase signal peptide fused to B. pumilus chloramphenicol acetyltransferase (Cat) are unable to export Cat protein into the growth medium. A series of tripartite protein fusions was constructed by inserting various lengths of the Cat sequences between the levansucrase signal peptide and staphylococcal protein A or Escherichia coli alkaline phosphatase. Biochemical characterization of the various Cat protein fusions revealed that multiple regions in the Cat protein were causing the export defect. PMID- 8366056 TI - Plasmids from two morphologically distinct cyanobacterial strains share a novel replication origin. AB - A 2.9-kbp replication origin from a plasmid endogenous to the filamentous cyanobacterium Fremyella diplosiphon UTEX 481 was genetically characterized and sequenced. Deletion analysis of the 2.9-kbp DNA fragment delimited the minimum region necessary for replication in F. diplosiphon Fd33 to approximately 2.5 kbp. DNA sequence analysis revealed that the F. diplosiphon plasmid replication origin is structurally very similar to and shares significant identity with the 1.75-kbp replication origin reported for plasmid pDU1, isolated from the morphologically distinct cyanobacterium Nostoc sp. strain PCC 7524. Each cyanobacterial plasmid replication origin includes a large open reading frame that predicts a conserved protein of unknown function; the predicted proteins of the replication origins are of similar sizes and 30% identical in amino acid sequence. Each cyanobacterial plasmid replication origin also possesses a region of dyad symmetry approximately 300 bp upstream of the conserved open reading frame. PMID- 8366057 TI - The chimeric VirA-tar receptor protein is locked into a highly responsive state. AB - The wild-type VirA protein is known to be responsive not only to phenolic compounds but also to sugars via the ChvE protein (G. A. Cangelosi, R. G. Ankenbauer, and E. W. Nester, Proc. Natl. Acad. Sci. USA 87:6708-6712, 1990, and N. Shimoda, A. Toyoda-Yamamoto, J. Nagamine, S. Usami, M. Katayama, Y. Sakagami, and Y. Machida, Proc. Natl. Acad. Sci. USA 87:6684-6688, 1990). It is shown here that the mutant VirA(Ser-44, Arg-45) protein and the chimeric VirA-Tar protein are no longer responsive to sugars and the ChvE protein. However, whereas the chimeric VirA-Tar protein was found to be locked in a highly responsive state, the VirA(Ser-44, Arg-45) mutant protein appeared to be locked in a low responsive state. This difference turned out to be important for tumorigenicity of the host strains in virulence assays on Kalanchoe daigremontiana. PMID- 8366058 TI - General distribution of the nitrogen control gene ntcA in cyanobacteria. AB - The ntcA gene from Synechococcus sp. strain PCC 7942 encodes a regulatory protein which is required for the expression of all of the genes known to be subject to repression by ammonium in that cyanobacterium. Homologs to ntcA have now been cloned by hybridization from the cyanobacteria Synechocystis sp. strain PCC 6803 and Anabaena sp. strain PCC 7120. Sequence analysis has shown that these ntcA genes would encode polypeptides strongly similar (77 to 79% identity) to the Synechococcus NtcA protein. Sequences hybridizing to ntcA have been detected in the genomes of nine other cyanobacteria that were tested, including strains of the genera Anabaena, Calothrix, Fischerella, Nostoc, Pseudoanabaena, Synechococcus, and Synechocystis. PMID- 8366060 TI - Clarification of the Escherichia coli genetic map in the 92-minute region containing the ubiCA operon and the plsB, dgk, lexA, and dinF genes. PMID- 8366061 TI - Location of the 7 alpha-hydroxysteroid dehydrogenase gene (hdhA) on the physical map of the Escherichia coli chromosome. PMID- 8366059 TI - Density fluctuation during the cell cycle in the defective vacuolar morphology mutants of Saccharomyces cerevisiae. AB - The buoyant densities of the yeast cells of defective vacuolar morphology mutants were examined by equilibrium sedimentation centrifugation in a Percoll density gradient. These vacuoleless mutants also show density fluctuation as wild-type cells during the cell cycle. This suggests that morphological changes of the vacuole are not related to cyclic density fluctuation in Saccharomyces cerevisiae. PMID- 8366063 TI - Physical and genetic mapping of the tag gene on the Escherichia coli chromosome. PMID- 8366062 TI - Location of the prlC (opdA) gene on the physical map of Escherichia coli. PMID- 8366064 TI - Location of the gltP gene on the physical map of Escherichia coli K-12. PMID- 8366065 TI - Physical map location of the rffC and rffA genes of Escherichia coli. PMID- 8366066 TI - Genetic and physical mapping of the regulatory gene csrA on the Escherichia coli K-12 chromosome. PMID- 8366067 TI - Location of the udk gene on the physical map of Escherichia coli. PMID- 8366068 TI - Structure and function of mammalian facilitative sugar transporters. PMID- 8366069 TI - Biogenesis of the mitochondrial receptor complex. Two receptors are required for binding of MOM38 to the outer membrane surface. AB - Targeting of preproteins to mitochondria is mediated by the receptor complex in the outer membrane that contains two import receptors and the general insertion pore with MOM38 (38-kDa mitochondrial outer membrane protein) as major constituent. As all components of the receptor complex have to be imported from the cytosol themselves, the specificity of their targeting is fundamental for the correct assembly of mitochondria. None of the receptors is involved in its own import; the precursor of the main receptor MOM19 is even targeted without any surface receptor but directly assembles with MOM38. We report that import of the precursor of MOM38 strictly depended on surface receptors. The import followed a new highly selective mechanism in that both receptors together were needed for the specific binding of the preprotein to the outer membrane surface, which was followed by its assembly into the receptor complex. These findings suggest that targeting of the mitochondrial targeting components involves a complex system of mutual specificity control, ensuring a selective assembly of the components into preexisting import sites. PMID- 8366071 TI - The catalytic mechanism of glutathione S-transferase (GST). Spectroscopic determination of the pKa of Tyr-9 in rat alpha 1-1 GST. AB - The rat alpha 1-1 glutathione S-transferase (GST) contains a single, non essential tryptophan and only 8 tyrosines in each subunit. One of these tyrosines, Tyr-9, hydrogen bonds to the substrate glutathione and stabilizes the nucleophilic thiolate anion. Two mutant proteins that allow for the spectrocopic determination of the pKa of this catalytic residue have been constructed. The W21F mutant provides a fully active GST with no tryptophans, and the double mutant W21F/Y9F lacks both tryptophan and the active site tyrosine. The intrinsic fluorescence and absorbance properties of these mutants are dominated by tyrosine. Fluorescence emission, fluorescence excitation, and absorbance spectral changes of samples containing the W21F mutant at several pH values in the range 6.8-9.0 reveal a pH-dependent increase in the contribution of tyrosinate. No spectral changes are observed with the W21F/Y9F protein in this pH range. At pH 12.5, both proteins exhibit complete deprotonation of all tyrosines. The pKa of Tyr-9 determined from these spectroscopic changes is 8.3-8.5. The changes in absorbance at 250 and 295 nm correspond to titration of 0.95 +/- 0.29 tyrosines/subunit in the W21F protein between pH 6.9 and 9.3. Moreover, addition of the inhibitor S-hexylglutathione results in an apparent increase in the pKa of Tyr-9. Together, these results indicate that the catalytically active Tyr of GSTs has a pKa value that is 1.8-2.0 pKa units below tyrosine in solution. It is likely that this decrease in the pKa of Tyr-9 contributes to catalysis by altering the equilibrium position of the proton shared between Tyr-9 and GSH, and this active site residue may function as a general base catalyst in addition to a hydrogen bond donor. PMID- 8366070 TI - Molecular cloning, identification, and sequence of the hyaluronan synthase gene from group A Streptococcus pyogenes. AB - The hyaluronan (HA) synthase of Group A Streptococci has been identified by transposon mutagenesis and deletion analysis. The genes for the HA synthase and a recently identified UDP-Glc dehydrogenase (Dougherty, B. A., and van de Rijn, I. (1993) J. Biol. Chem. 268, 7118-7124) reside on a contiguous stretch of 3.2 kilobase pair DNA that can direct HA biosynthesis in Enterococcus faecalis and Escherichia coli as well as mutant Streptococcus (DeAngelis, P. L., Papaconstantinou, J., and Weigel, P. H. (1993) J. Biol. Chem. 268, 14568-14571). The synthase contains 395 residues (calculated Mr = 45,063) and migrates on SDS PAGE with a molecular mass of 42 kDa. E. coli K5, which synthesizes UDP glucuronic acid for production of its endogenous capsular polysaccharide, can make HA if it contains a plasmid encoding the intact 42-kDa protein. E. coli SURE or chi 1448 cells containing the same construct, however, cannot produce HA since these strains cannot make both required sugar nucleotide precursors. The HA synthase is predicted to be an integral membrane protein with four membrane associated helices, which is consistent with the location of the enzyme activity in Streptococci. There is significant homology between the HA synthase and the Rhizobium nodC gene product, an enzyme that synthesizes chitin-like oligomers. This is the first description at the molecular level of an enzyme shown to synthesize a glycosaminoglycan. PMID- 8366072 TI - Assembly of the primosome of DNA replication in Escherichia coli. AB - Assembly of the Escherichia coli primosome requires six proteins, PriA, PriB, PriC, DnaB, DnaC, and DnaT, acting at a primosome assembly site (pas) on an SSB coated single-stranded (ss) DNA. Assembly is initiated by interactions of PriA and PriB with ssDNA and the pas. PriC, DnaB, DnaC, and DnaT then act on the PriA PriB-DNA complex to yield the primosome. In the primosome, the dATPase (ATPase) of PriA becomes hyper-activated. In addition, the assembled primosome appears to block the pas, preventing it from activating additional PriA molecules. Either ATP alone or dATP in combination with GTP is sufficient for primosome assembly, while ATP or GTP provides for its maintenance during isolation. These nucleotide requirements can be reconciled with the need for ATP or dATP for DnaB-DnaC complex formation and hydrolysis of ATP or GTP by DnaB when it binds ssDNA. Such isolated primosomes contain a dATPase, the hallmark of PriA, and a GTPase indicative of DnaB. Further studies indicate that the isolated primosome contains the PriB replication activity in addition to PriA and DnaB. PMID- 8366073 TI - Peptide binding to protein disulfide isomerase occurs at a site distinct from the active sites. AB - Protein disulfide isomerase (PDI) is a multifunctional protein resident in the lumen of the rough endoplasmic reticulum that facilitates protein folding via disulfide bond isomerization. Previously we determined that PDI binds a variety of peptides that can be covalently attached to this protein via a photoreactive cross-linker. We have now investigated the relationship between the peptide binding site and the ability of PDI to catalyze disulfide bond isomerization. PDI has two identical sequences, -WCGHCK-, that have been demonstrated to be important in PDI-catalyzed disulfide isomerization. We have found that other proteins containing these thioredoxin-like active site sequences do not bind the photoreactive peptide probes. Moreover, although chemical modification of the 2 cysteines within the thioredoxin-like active site regions completely inhibits PDI catalyzed disulfide isomerization, these modifications do not affect peptide binding by PDI. Both of these observations suggest that peptide binding occurs at a site other than the putative PDI active sites. To localize the site in PDI at which binding occurs, we used a radiolabeled peptide photoaffinity probe. Peptide fragments generated by cleavage of 125I-peptide-labeled PDI with cyanogen bromide yielded a single 8-kDa polypeptide fragment containing the 125I-labeled peptide site, but neither of the putative catalytic sites of PDI. An 125I-labeled tryptic peptide was generated from this cyanogen bromide fragment and determined by microsequencing to contain residues 451-476 of PDI; this 26-residue peptide is noteworthy because of its extremely high content of acidic amino acids. Based on these findings we conclude that the peptide binding site is located in the COOH terminal domain of the protein, and it is distinct from the two active sites for PDI-catalyzed disulfide isomerization and from the region of PDI that has estrogen receptor sequence similarity. PMID- 8366074 TI - Comparison of antiparallel and parallel two-stranded alpha-helical coiled-coils. Design, synthesis, and characterization. AB - An antiparallel coiled-coil has been designed and characterized as a model for studying protein folding and assembly. This heterostranded antiparallel coiled coil was formed by an interchain disulfide bond between cysteine residues at position 2 of one chain and at position 33 of the other chain. Each peptide chain has 35 residues which are composed of five heptad repeats of the sequence K-L-E-A L-E-G with a single Leu-->Ala substitution at position 16. Two homostranded parallel coiled-coils were also formed as co-products of the oxidation reaction to form the interchain disulfide bond. The CD spectra of the parallel and antiparallel peptides were very similar and their high molar ellipticities at 220 nm did not increase in the presence of 50% trifluoroethanol. These data suggest that, like the parallel peptides, the antiparallel peptide also exists in a coiled-coil structure. Urea and guanidine hydrochloride denaturation studies, in conjunction with molecular modeling studies, suggest that there are no physical restrictions to the packing of hydrophobic residues in an antiparallel coiled coil. However, interchain electrostatic interactions can have positive or negative contributions to the overall stability of the disulfide-bridged coiled coil. In addition, interchain electrostatic interactions appear to play a major role in protein folding by controlling the parallel or antiparallel alignment of the alpha-helical polypeptide chains. This study is also for the first time providing us with a new understanding of the information that can be obtained from urea and guanidine hydrochloride denaturation studies of proteins concerning the contributions of hydrophobic and electrostatic interactions on stability. PMID- 8366075 TI - Comparative analysis of structurally defined heparin binding sequences reveals a distinct spatial distribution of basic residues. AB - Heparin, among the best studied glycosaminoglycans, is well known for its involvement in a variety of physiological processes. Many proteins, whose activities are modulated via heparin binding, were identified, and the consequences of their interaction with heparin were characterized. However, in the absence of solid structural information regarding heparin-protein complexes, the mechanism by which heparin operates at the molecular level is still obscure. The structure of such a complex is hereby explored via the identification of a common motif in heparin binding sequences. To avoid ambiguity we included in our data base only sequences that have been shown experimentally to be directly involved in heparin binding. Then, a comparison of the spatial distribution of basic residues was conducted among those peptides for which three-dimensional structures were defined. Using computer graphics techniques we were able to identify a unique distribution shared by all of these segments. Two basic amino acids (most frequently arginine) are located at about 20 A apart, facing opposite directions of an alpha-helix. Other basic amino acids are dispersed between these two residues, facing one side, while nonpolar residues face the opposite side, forming an amphipathic structure. The distribution of basic amino acids in other heparin binding sequences that preserves the same spatial arrangement seems to be compatible with a beta-strand structure. The 20-A interval accommodates a glycosaminoglycan pentasaccharide, and the spatial distribution of the basic residues suggests an intertwinement of the heparin-protein complex. The dynamics of such an interaction may provide a clue regarding the ensuing change in protein activity. PMID- 8366076 TI - Critical minimum length of the central helix in troponin C for the Ca2+ switch in muscular contraction. AB - In the troponin C (TnC) dumbbell, the NH2- and COOH-terminal lobes are well delineated, but the role of the central helix and especially the function of its long length remain doubtful. To study this, we used a cDNA construct encoding rabbit fast-twitch muscle TnC, comprising multiple restriction sequences to facilitate mutagenesis (Babu, A., Su, H., Ryu, Y. & Gulati, J. (1992) J. Biol. Chem. 267, 15469-15474). Systematically, we have deleted 3-12 amino acid residues from the central helix and examined their effects in maximally activated skinned muscle fibers. Limiting the deletions to 7 amino acid residues manifested little change in maximal force development (Sheng, Z., Francois, J. M., Hitchcock, S. E. & Potter, J. D. (1991) J. Biol. Chem. 266, 5711-5715). However, with further deletions, we now find that contractility was inhibited pari passu; by 12 deletions, the inhibition was complete. The critical minimum length for the central helix is thereby estimated as 27 A. The Ca2+ binding capacity (4 mol of Ca2+/mol of protein) as well as the structural characteristics (alpha-helicity by CD measurements and the fluorescence emitted by Tyr-109) indicated a well preserved global conformation of the short mutant. However, surprisingly, two of these short mutants filled each TnC slot under highly specific superloading conditions: one short molecule was taken up in EGTA solution, and the second molecule was captured and retained with Ca2+. They also rescued the contractile switch, evidently in a bimolecular reaction. Another short variant (putative skeletal fast muscle TnC-I-II), in which the NH2-terminal Ca(2+)-binding sites were incapacitated, failed to respond to superloading, indicating that sites III and IV could not substitute for sites I and II. The results suggest that a critical role of the central helix linker in TnC is to keep the two lobes optimally apart, evidently in proximity of their respective target sites on troponin I in the fiber. PMID- 8366077 TI - Probing the role of the carboxyl-terminal region of ferredoxin-NADP+ reductase by site-directed mutagenesis and deletion analysis. AB - The carboxyl-terminal region of plant ferredoxin-NADP+ reductases is formed by an invariant alpha-helix/loop/beta-strand, culminating in a conserved tyrosine that displays extensive interaction with the prosthetic group FAD. We have investigated the potential role of the terminal region in reductase function, by introducing mutations and deletions on pea ferredoxin-NADP+ reductase overexpressed in Escherichia coli. Replacement of the terminal tyrosine by tryptophan, phenylalanine, serine, and glycine resulted in a 2.2-, 2.0-, 22-, and 302-fold reduction, respectively, in kcat for the diaphorase reaction, whereas elimination of the tyrosine caused a 846-fold decrease in kcat. Km values were largely unaffected by the substitutions. Similar results were obtained when the mutants were assayed for cytochrome c reduction, indicating that aromaticity is the most important factor to the function of the tyrosine in catalysis. The presence of the phenol ring at the carboxyl-terminal position of wild-type reductase is important, but not an absolute requirement for enzyme function or FAD assembly. Deletion of the alpha-helix/beta-strand region prevented reductase proper folding in the bacterial host, while shortening of the terminal region by splicing 3 amino acids at the beginning of the alpha-helix produced a moderately soluble reductase, devoid of FAD and enzymatic activity. PMID- 8366078 TI - Structural and functional domains of apolipoprotein A-I within high density lipoproteins. AB - We prepared discoidal and spherical model high density lipoprotein (HDL) with apolipoprotein A-I and 1-palmitoyl-2-oleoyl phosphatidylcholine at various lipid:protein ratios and compared their reactivity with exo- and endopeptidases to that of human HDL2 and HDL3. Limited proteolysis with trypsin, Staphylococcus V8 protease, and elastase yielded a major stable peptide of 11,000-11,500 daltons under conditions which completely degraded lipid-free A-I. By Western blotting this protease-resistant fragment was shown to consist of the amino-terminal 90 100 residues of the A-I protein; the residues on the carboxyl side of this peptide are therefore protease-sensitive and appear to correlate with the putative "hinge" region, which is especially reactive with antibodies. The amino terminus was very resistant to digestion with a variety of aminopeptidases, whereas carboxypeptidases could remove up to 70 residues from the lipid-free A-I protein or 12-24 residues from A-I in various HDL. When these truncated forms of A-I, in combination with lipid, were used to examine binding interactions with rat hepatic plasma membranes, it was found that removal of up to 20-24 residues from the carboxyl terminus had no significant effect on binding, whereas removal of 70 residues completely eliminated specific binding to the membranes. Taken together, our data indicate that there is a protease-resistant domain constituted by the first 90 residues of A-I, which, in HDL, contain little of the class of amphipathic helix characteristic of the rest of the molecule and most likely form a structure dominated by protein-protein interactions. At the carboxyl end of the protein, there is a functional domain constituted by residues 149-219 that possesses the capacity to bind to proteins on hepatic membranes. PMID- 8366079 TI - Alpha-lactalbumin possesses a distinct zinc binding site. AB - It has been proposed that the binding of Zn2+ to alpha-lactalbumin switches the conformation to one akin to a state intermediate in the folding of the protein. However, the high resolution x-ray crystal structure of human alpha-lactalbumin Zn2+ complex at 1.7-A resolution (pH 7.6) does not reveal any significant change in conformation from the native state. The Zn2+ ion binds specifically in the "cleft" of alpha-lactalbumin (the region which forms the active site of the homologous protein lysozyme). This may suggest a possible role for Zn2+ binding in lactose synthase complex. The coordination of the Zn2+ ion involves a symmetry related molecule in the crystal, the crystal contacts being stabilized by a SO4(2 ) ion bound at the interface between three molecules. PMID- 8366080 TI - Two base pairs at -9 and -8 distinguish between the bacteriophage T7 and SP6 promoters. AB - Bacteriophage T7 and SP6 RNA polymerases and their promoters share a high degree of their primary structure homology, but each polymerase exclusively recognizes its own promoter sequence. To reveal the molecular basis of this specificity, 4 base pairs at positions -12, -10, -9, and -8 of the T7 promoter were substituted individually and multiply by SP6 promoter-specific base pairs, and 3 base pairs at -10, -9, and -8 of the SP6 promoter were replaced by T7 promoter-specific base pairs. Promoter activities of 28 sequences were measured in vitro with T7 and SP6 polymerases separately under optimal conditions at 6 mM MgCl2. Single and double substitutions at -12 and -10 do not significantly affect the T7 promoter activity, although they are almost exclusively conserved among T7 genomic promoters. Changes at -10 of SP6 promoter hardly affect the activity. However, any T7 variants that contain either or both changes at -9 and -8 show greatly reduced activity. Interestingly, the double substitution at -9 and -8 yields significant SP6 promoter activities and virtually no T7 promoter activity. Furthermore, the SP6 promoter variants with both T7-specific -9C and -8T show good T7 promoter activities, although they still show some SP6 promoter activities. However, under high salt conditions (either 20 mM MgCl2 or 100 mM NaCl plus 6 mM MgCl2), they show only slight SP6 promoter activity. No other SP6 variants show any T7 promoter activity. All these results indicate that the 2 base pairs at -9 and -8 of both the T7 and SP6 promoters are the primary (if not the only) determinants of specificity and that the hierarchy of importance of positions for promoter activity is -8, -9 > > -10 > -12. Also, a phylogenic relationship among the T3, T7, K11, and SP6 promoters is suggested based on dissimilarities in their sequences from -12 to -8. PMID- 8366081 TI - Dihydropyrimidine dehydrogenase. Kinetic mechanism for reduction of uracil by NADPH. AB - Steady-state and pre-steady-state kinetic data were used to determine the kinetic mechanism for bovine liver dihydropyrimidine dehydrogenase (DPDase). Steady-state kinetic data suggested a random rapid-equilibrium mechanism with Km values for NADPH and uracil of 0.12 microM and 0.8 microM, respectively, and a kcat of 1.6 s 1 in Tris buffer at pH 8.0 and 37 degrees C. The dissociation constant of DPDase for NADPH at 25 degrees C in the absence of uracil (0.09 microM) was similar to the Km for NADPH. DPDase also catalyzed the exchange of tritium in [4S-3H,4R 1H]NADP3H with solvent protons in the absence of uracil. DPDase inactivated by 5 ethynyluracil, which covalently modifies the enzyme at the uracil binding site, catalyzed the exchange reaction at the same rate (1 s-1) as native enzyme. Thus, the interaction of NADPH with DPDase was independent of the uracil binding site. Because DPDase catalyzed the exchange of deuterium in [4S-2H,4R-1H]NADP2H with solvent protons with a rate constant of 5.4 s-1, which was significantly larger than that for tritium, the analogous rate constant for exchange of the 4-hydrogen in NADPH must be significantly larger than 5 s-1. Consequently, intermediates on the exchange pathway were kinetically competent to participate in the reduction of uracil by NADPH (kcat = 1.6 s-1). Rate constants for reduction of DPDase by NADPH and 5,6-dihydrouracil were several orders of magnitude greater than kcat. The rate constants for dissociation of E.NADP+ (15 s-1) and for dissociation of E.5,6-dihydrouracil (> 250 s-1) were also greater than kcat. These results supported a random rapid-equilibrium kinetic mechanism and suggested kcat was an internal electron transfer between enzymic prosthetic groups. PMID- 8366082 TI - Functions of potA and potD proteins in spermidine-preferential uptake system in Escherichia coli. AB - Functions of potA and -D proteins in the spermidine-preferential uptake system, which consists of potA, -B, -C, and -D proteins, were studied. Spermidine uptake activity was lost when the gene for potA or potD protein was disrupted, and transformation of the cells with potA or potD gene recovered the uptake activity. PotD protein was found to bind spermidine with a 3.2 microM dissociation constant. Spermidine uptake by membrane vesicles prepared from Escherichia coli DR112 containing the genes for potA, -B, and -C proteins was strongly dependent on the addition of potD protein, and its optimal concentration was 5 microM when 10 microM spermidine was used as substrate. The ATP dependence of spermidine uptake was examined with the atp mutant of E. coli. The uptake was completely dependent on ATP. When the membrane potential was extinguished by carbonyl cyanide m-chlorophenylhydrazone, the uptake activity was decreased by 60% even if ATP existed. This suggests that the membrane potential is also involved in the spermidine uptake. ATP was found to bind to potA protein. In the spermidine transport-deficient mutant E. coli NH1596, valine 135 of potA protein, which is located between two consensus amino acid sequences for nucleotide binding, was replaced by methionine. Although the amount of mutated potA protein expressed in E. coli cells was the same as that of normal potA protein and the mutated protein was membrane-associated, no significant spermidine uptake was observed. The results taken together indicate that potA and -D proteins are absolutely necessary for spermidine uptake in conjunction with the two channel forming proteins (potB and -C). PMID- 8366083 TI - Triggering of cellulase biosynthesis by cellulose in Trichoderma reesei. Involvement of a constitutive, sophorose-inducible, glucose-inhibited beta diglucoside permease. AB - We prepared [U-14C]cellobiose by cultivating Acetobacter pasteurianus in the presence of [U-14C]glucose and hydrolyzing the [U-14C]cellulose formed with beta glucosidase-free cellulase from Trichoderma reesei. This 14C-labeled cellobiose was used to investigate the presence of an uptake system for cellobiose in T. reesei. Evidence was obtained for the presence of a high affinity (Km for cellobiose 0.3 microM) but low activity (2.5 milliunits/mg fungal dry weight) cellobiose permease. The permease is formed constitutively, but higher levels are formed after addition of sophorose (glucosyl-beta-1,2-diglucoside), a reputed cellulase inducer. The permease appears to be specific for beta-diglucosides, as the uptake of [U-14C]cellobiose is inhibited by sophorose, gentiobiose (glucosyl beta-1,3-glucoside), and cellobiose. Under these conditions, cellooligodextrines (n, 4-7; final concentration, 1 mM) are not inhibitors. Glucose, but no other monosaccharides, inhibits the permease. The hypersecretory mutant T. reesei RUT C 30 exhibits elevated permease activities, whereas in T. reesei QM 9979, a mutant strain defective in the induction of cellulases by cellulose or sophorose, strongly reduced permease activities were demonstrated. The results stress a hitherto not recognized point of control in the induction of cellulases by T. reesei at the level of uptake of cellulose oligosaccharides. PMID- 8366084 TI - Mechanism and energetics of the secondary phosphate transport system of Acinetobacter johnsonii 210A. AB - The mechanism and energetics of the secondary Pi transport system of A. johnsonii were studied in membrane vesicles and proteoliposomes in which the transport protein was functionally reconstituted. Pi uptake is strictly dependent on the presence of divalent cations, like Mg2+, Ca2+, Mn2+, or Co2+. These cations form a MeHPO4 complex with up to 87% of the Pi present in the incubation mixture, suggesting that divalent cations and Pi are co-transported via a metal-phosphate chelate. Metal-phosphate uptake is driven by the proton motive force (interior negative and alkaline). The metal-phosphate/proton stoichiometry was close to unity. The transport system mediates efflux and homologous exchange of metal phosphate, but not heterologous exchange of metal-phosphate and glycerol-3-P or glucose-6-P. Exchange and counterflow were essentially pH-independent while efflux and uptake increased with increasing pH. Efflux was inhibited by the proton motive force, whereas exchange was inhibited by the membrane potential only. These observations are consistent with an ordered mechanism for binding and dissociation of metal-phosphate and proton to and from the carrier protein and point to the recycling of a positively charged, protonated carrier protein during exchange. PMID- 8366085 TI - Identification of an uncleavable targeting signal in the 70-kilodalton spinach chloroplast outer envelope membrane protein. AB - A cDNA clone encoding a cognate 70-kDa heat shock protein from the spinach chloroplast outer envelope (SCE70) was recently characterized (Ko, K., Bornemisza, O., Kourtz, L., Ko, Z. W., Plaxton, W. C., and Cashmore, A. R. (1992) J. Biol. Chem. 267, 2986-2993). Initial studies revealed that SCE70 is targeted to the chloroplast outer envelope membrane without further processing. To determine whether SCE70 possesses a "targeting domain," we tested the targeting ability of SCE70 proteins with various carboxyl- and amino-terminal deletions. Carboxyl-terminal deletions of up to 60% of the protein had no apparent effect on the targeting ability of SCE70. Amino-terminal deletions abolished targeting to the chloroplast except when the extreme NH2-terminal 48-amino acid sequence was retained. We further assessed the chloroplast-targeting ability of the NH2 terminal 48 amino acids by fusing to the foreign protein, mouse dihydrofolate reductase (DHFR). The resulting fusion protein, SCE70-DHFR, was localized to the outer envelope membrane of isolated chloroplasts. SCE70-DHFR exhibited targeting characteristics similar to native SCE70. The targeting of SCE70-DHFR was inhibited effectively by anti-SCE70 antibodies. Immunoprecipitation and chemical cross-linking experiments revealed that SCE70-DHFR is targeted to the same complex as SCE70 in the chloroplast envelope. These results suggest that the extreme NH2 terminus of SCE70 is required for directing SCE70 to a destination in the chloroplast outer envelope membrane, possibly through assembling the polypeptide into a protein complex. PMID- 8366087 TI - Identity of Escherichia coli tRNA(Cys) determined by nucleotides in three regions of tRNA tertiary structure. AB - The in vivo aminoacylation specificity of tRNA(Cys) was studied with mutants of opal and amber suppressor tRNAs in Escherichia coli. This specificity depends not only on nucleotides in the acceptor end and anticodon of tRNA(Cys), but also on nucleotides in the dihydrouridine stem and loop and the variable loop that interact, forming the complex core of tRNA tertiary structure. PMID- 8366086 TI - Nonbiased identification of DNA sequences that bind thyroid hormone receptor alpha 1 with high affinity. AB - Thyroid hormone receptors are transcription factors that bind to specific DNA sequences and regulate gene expression in a ligand-dependent manner. Although thyroid hormone receptors are known to bind to the hexamer 5'-AGGTCA, it is not known if this represents the optimal binding site. Therefore, a nonbiased strategy was used to identify DNA sequences which bind thyroid hormone receptor alpha 1 with high affinity. Such DNA sequences were isolated from a pool of random sequences using a strategy combining an electrophoretic mobility shift assay with the polymerase chain reaction. It was found that thyroid hormone receptor alpha 1 binds with highest affinity to the octamer 5'-TAAGGTCA. Mutation of the two 5'-nucleotides decreased the affinity of thyroid hormone receptor alpha 1 for this DNA sequence approximately 5-fold, and the importance of those nucleotides in receptor binding was confirmed by DNA footprinting. A single copy of the octamer sequence (but not the hexamer AGGTCA) could impart T3 responsiveness to a heterologous promoter in a transient transfection assay. The results indicate that the optimal binding site for thyroid hormone receptor alpha 1 is 2 base pairs larger than previously thought, and that a single binding site can function as a response element. In addition, we speculate that the optimal binding sites for thyroid hormone, vitamin D, and retinoic acid receptors may not be identical, as had previously been thought. PMID- 8366088 TI - Bradykinin-induced cytosolic Ca2+ oscillations and inositol tetrakisphosphate induced Ca2+ influx in voltage-clamped ras-transformed NIH/3T3 fibroblasts. AB - Microspectrofluorometry (fura-2) was combined with the whole-cell patch-clamp technique to study bradykinin-activated calcium (Ca2+) influx in single control or v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts. Application of bradykinin on DT cells, but not on control NIH/3T3 cells, evoked cytosolic Ca2+ oscillations in the presence of extracellular Ca2+, but not in the absence of external Ca2+. This effect of zero external Ca2+ concentration could be mimicked by holding at depolarized membrane potentials. Cytosolic Ca2+ oscillations observed at holding potentials of -20 to -80 mV were terminated by holding at -10 mV or more depolarized potentials. The frequency of Ca2+ oscillations increased with membrane hyperpolarization. Bradykinin significantly enhanced the hyperpolarization-induced increases in the intracellular free Ca2+ concentration ([Ca2+]i) upon membrane hyperpolarization only in DT cells but not in control cells. No [Ca2+]i increase upon hyperpolarization was observed in bradykinin stimulated DT cells in the absence of external Ca2+, suggesting that bradykinin activates Ca2+ influx. [Ca2+]i increased upon application of inositol 1,3,4,5 tetrakisphosphate (Ins(1,3,4,5)P4) into control and DT cells in an extracellular Ca(2+)-dependent manner, indicating that NIH/3T3 fibroblasts have an Ins(1,3,4,5)P4-gated Ca2+ influx pathway. Ins-(1,3,4,5)P4, however, produced the sustained [Ca2+]i increase in DT cells, but not in control NIH/3T3 cells, suggesting that ras may lock the Ca2+ influx pathway at the activated state. Cytosolic Ca2+ oscillations, bradykinin-enhanced Ca2+ influx, and Ins(1,3,4,5)P4 induced Ca2+ influx were all similar in that activity was increased by membrane hyperpolarization. The results suggest that bradykinin-induced cytosolic Ca2+ oscillations in ras-transformed NIH/3T3 cells are maintained by bradykinin activated continuous Ca2+ influx which may use Ins(1,3,4,5)P4 as an intracellular messenger. PMID- 8366089 TI - Evidence for two DNA repair enzymes for 8-hydroxyguanine (7,8-dihydro-8 oxoguanine) in human cells. AB - Two DNA repair enzymes for 8-hydroxyguanine (also known as 7,8-dihydro-8 oxoguanine; OH8Gua, oxo8Gua) have been identified in human HeLa cell nuclear extract. One is OH8Gua-glycosylase and the other is OH8Gua-endonuclease that lacks OH8Gua-glycosylase activity. They were separated by heparin-Sepharose column chromatography and characterized by endonuclease nicking assay or by measuring the OH8Gua released from substrate DNA using high pressure liquid chromatography-electrochemical detection. Both OH8Gua repair enzymes act only on the OH8Gua-containing strand of the duplex substrate DNA containing OH8Gua/C, OH8Gua/T, or OH8Gua/G. DNA containing OH8Gua/A base pair was very poor substrate for either enzymes. OH8Gua-endonuclease simultaneously cleaves phosphodiester bonds on both sides of the OH8Gua residue, leaving 5'-hydroxy and 3'-hydroxy groups. PMID- 8366090 TI - LE-ACS4, a fruit ripening and wound-induced 1-aminocyclopropane-1-carboxylate synthase gene of tomato (Lycopersicon esculentum). Expression in Escherichia coli, structural characterization, expression characteristics, and phylogenetic analysis. AB - ACC (1-aminocyclopropane-1-carboxylic acid) synthase is the key regulatory enzyme in the biosynthetic pathway of the plant hormone ethylene and is encoded by a highly divergent multigene family in tomato (Rottmann, W. H., Peter, G. F., Oeller, P. W., Keller, J. A., Shen, N. F., Nagy, B. P., Taylor, L. P., Campbell, A. D., and Theologis, A. (1991) J. Mol. Biol. 222, 937-961). Two members of the family, LE-ACS2 and LE-ACS4, are induced during fruit ripening and upon treatment of mature green fruits with exogenous ethylene (C2H4) in a dose-dependent manner. Both genes are superinduced by wounding of pericarp tissue during various stages of ripening. The wound-induced accumulation of LE-ACS2 mRNA is more rapid and greater than that of LE-ACS4. Both mRNAs accumulate in the absence of protein synthesis, suggesting that their induction is a primary response to the inducer. The LE-ACS4 gene was isolated and structurally characterized. The function of the LE-ACS4 protein (53,509 Da, pI 5.4) was verified by expression experiments in Escherichia coli. The promoters of LE-ACS2 and LE-ACS4 contain potential cis acting regulatory elements responsible for induction by ethylene, wounding, and anaerobiosis. In addition, elements for binding the transcriptional factors EmBP1, GBF-1, and OCSBF-1 are also present. Phylogenetic analysis of 20 ACC synthases from dicots and monocots indicate that the LE-ACS2 and LE-ACS4 proteins belong to an unique sublineage that includes an additional member of the tobacco family, NT-ACS1. The divergence of this sublineage is a relatively recent event in the evolution of ACC synthase protein. PMID- 8366091 TI - The Saccharomyces cerevisiae LOS1 gene involved in pre-tRNA splicing encodes a nuclear protein that behaves as a component of the nuclear matrix. AB - Mutations of the Saccharomyces cerevisiae LOS1 gene cause the accumulation of end matured intron-containing pre-tRNAs at elevated temperatures. In an effort to decipher the role of the LOS1 protein in pre-tRNA splicing, we have analyzed the LOS1 gene and its protein product. The LOS1 gene is located on the left arm of chromosome XI and the order of genes in this area of the chromosome is .... URA1 ... SAC1 TRP3 UBA1 STE6 LOS1 .... FAS1..... The LOS1 open reading frame encodes a putative protein of 1100 amino acids that shows no significant homology to other genes. The LOS1 open reading frame was tagged with the influenza virus hemagglutinin epitope recognized by the 12CA5 antibody. The 12CA5 antibody recognizes an epitope-tagged protein of the size predicted by the LOS1 open reading frame. Using this antibody for indirect immunofluorescence and cell fractionation studies we show that the LOS1 protein is located in nuclei. Los1p cannot be extracted from nuclei by treatment with nucleases, salts, or Triton X 100. This insolubility suggests that Los1p is a component of the nucleoskeleton. We propose that LOS1 mutations may affect pre-tRNA processing via alteration of the nuclear matrix. PMID- 8366092 TI - NGFI-A gene expression is necessary for T lymphocyte proliferation. AB - NGFI-A is an immediate early gene, encoding a zinc finger protein, rapidly activated after mitogenic stimulation. NGFI-A gene expression was found to be rapidly and transiently induced after interleukin-2 (IL-2) stimulation of G1 lymphoblasts, as well as during the G0/G1 transition, when stimulated with concanavalin A (ConA). Activation of both Ca2+ and protein kinase C pathways, separately, in quiescent T lymphocytes produced a partial induction of this gene; however, both stimuli together are necessary to obtain a full response. ConA induced activation of NGFI-A in quiescent cells was inhibited by immunosuppressors. 8-Bromo-cAMP was able to inhibit the expression of this gene in G1 lymphoblasts after IL-2 stimulation, but failed to interfere with the ConA induced expression in quiescent T lymphocytes. Exposure of T cells to an NGFI-A antisense oligonucleotide blocked the ConA- and IL-2-induced proliferation of the cells, measured as thymidine incorporation and cell number. This inhibition provides direct evidence that the early gene NGFI-A plays a regulatory role in growth control processes of lymphocytes and that its expression is essential for cellular proliferation. PMID- 8366093 TI - Amino-terminal topology of thromboxane synthase in the endoplasmic reticulum. AB - The membrane topology of the NH2-terminal portion of human thromboxane synthase (TXS), a member of the cytochrome P450 superfamily, has been investigated. By sequence alignment, the first 6 residues of the mature TXS polypeptide are likely to form a distinctive "tail" structure not found in many other mammalian cytochromes P450 in the endoplasmic reticulum membrane. Peptides with either the ultimate 10 or 15 residues of the NH2 terminus of TXS were synthesized and used to produce site-directed antibodies. The resulting peptide antibodies were highly specific and recognized human TXS, as shown by binding assays and Western blot analysis. Binding of the peptide antibodies to recombinant TXS in transfected COS 1 and to endogenous TXS in THP-1 cells was analyzed by immunocytochemistry. Selective permeabilization of the plasma membrane to immunoglobulin was achieved with streptolysin O; general permeabilization, including the endoplasmic reticulum membrane, was accomplished with Triton X-100. Permeabilization of the plasma membrane was sufficient to produce binding of both peptide antibodies to their epitopes, indicating that the epitopes for both of the peptide antibodies were exposed on the cytoplasmic side of the endoplasmic reticulum membrane. The results with the peptide antibodies provide direct experimental evidence supporting the topological model for membrane-bound cytochrome P450 proposed by Nelson and Strobel (Nelson, D. R., and Strobel, H. W. (1988) J. Biol. Chem. 263, 6038-6050), in which the NH2 terminus is oriented toward the cytoplasmic side of the endoplasmic reticulum membrane. PMID- 8366094 TI - Insulin and okadaic acid induce Rab4 redistribution in adipocytes. AB - Insulin stimulation of glucose transport involves the translocation of vesicles containing the glucose transporter Glut 4 to the plasma membrane. Rab proteins, which have been implicated in the regulation of vesicular traffic, were studied in adipocytes. Rab3B, Rab3C, Rab4, and Rab8 were detected, but Rab3A was not. In the absence of insulin, Rab3B and Rab3C were cytosolic, while Rab4 and Rab8 were associated with membranes. Only Rab4 distribution was modified by insulin. In unstimulated adipocytes, most of Rab4 was found in a low density microsomal fraction, which also contained the majority of Glut 4. After insulin treatment, a 50% decrease in Rab4 content was observed, concomitantly with a departure of transporters to the plasma membrane. The dose responses for the departure of Glut 4 and Rab4 from the microsomal fractions were superimposable, half-maximal effects being obtained with 0.1 nM insulin. Rab4 was redistributed to the cytosol and its movement was reversed by insulin withdrawal. When Glut 4-containing vesicles were immunopurified with antibodies to Glut 4, Rab4 was found in the immune pellets, suggesting that Rab4 was tightly associated with the vesicles. Okadaic acid, an inhibitor of phosphatases 1 and 2A that is known to stimulate Glut 4 translocation, caused the same movement of Rab4 from low density microsomal fraction to the cytosol, while the phorbol ester 12-O tetradecanoylphorbol-13-acetate had no effect. We suggest that insulin and okadaic acid induce a cycling of Rab4 from a vesicular fraction containing the Glut 4 transporter to the cytosol and that this cycling may participate in the insulin stimulatory action on glucose transporter translocation. PMID- 8366095 TI - Myocyte-specific enhancer-binding factor (MEF-2) regulates alpha-cardiac myosin heavy chain gene expression in vitro and in vivo. AB - A myocyte-specific enhancer-binding factor (MEF-2) DNA binding site was identified in the rat alpha-myosin heavy chain (MHC) gene adjacent to the E-box binding site for alpha-MHC binding factor-2 (BF-2). Mutation of the MEF-2 site, within the context of the full-length promoter, reduced activity by 85 and 80% in neonatal cardiomyocytes and the adult heart, respectively. Mutation of the BF-2 site reduced activity approximately 70% in both models. A MEF-2/BF-2 double mutant gave significantly less activity than the BF-2 mutant but not the MEF-2 mutant, suggesting the possibility that BF-2 and MEF-2 interact. Mutations in MEF 2, which decreased functional activity, also abolished MEF-2 DNA binding activity. MEF-2 DNA binding activity was present in the developing heart, reached a peak in the late fetal and early neonatal stages, and then declined to low levels in the adult heart. The adult levels were sufficient to support alpha-MHC gene expression. MEF-2 activity was increased 2-3-fold in the adult heart subjected to a pressure or volume overload. Two working models are proposed as possible explanations of the antithetic relationship between MEF-2 levels and alpha-MHC gene expression. PMID- 8366096 TI - Molecular cloning and expression of GRK6. A new member of the G protein-coupled receptor kinase family. AB - G protein-coupled receptor kinases (GRK), such as the beta-adrenergic receptor kinase (beta ARK) and rhodopsin kinase, specifically phosphorylate the activated form of G protein-coupled receptors. To identify additional members of the GRK family, we screened a human heart cDNA library by low stringency hybridization using the catalytic domains of two beta ARK isoforms. Here we report the isolation of a cDNA that encodes a 576-amino-acid protein kinase, termed GRK6, that has significant homology with GRK5 (70.1% amino acid identity), IT11 (68.5%), rhodopsin kinase (47.1%), and beta ARK (37.4%). RNA blot analysis of GRK6 with selected human tissues reveals two distinct mRNAs of 3 and 2.4 kilobases with a distribution very similar to that of beta ARK (i.e. brain, skeletal muscle > pancreas > heart, lung, kidney, placenta > liver). GRK6, overexpressed in Sf9 insect cells using the baculovirus system, was able to phosphorylate both the beta 2-adrenergic receptor and rhodopsin in a stimulus dependent fashion, although it was significantly less active then beta ARK on these substrates. These data extend the family of GRKs and suggest that GRK6 may have a substrate specificity quite distinct from beta ARK and rhodopsin kinase. PMID- 8366097 TI - Influence of 3' half-site sequence of NF-kappa B motifs on the binding of lipopolysaccharide-activatable macrophage NF-kappa B proteins. AB - Lipopolysaccharide treatment of mouse macrophage-like J774 cells was found to result in the activation of three different nuclear proteins which specifically bind to oligonucleotide containing the NF-kappa B motif of the human immunodeficiency virus (HIV) gene. These are designated as NF-kappa B1, -kappa B2, and -kappa B3, according to their electrophoretic mobilities (fast, intermediate, and slow, respectively). Immunological and UV cross-linking studies showed that NF-kappa B1 consists of only p50 subunit, whereas both NF-kappa B2 and -kappa B3 contain NF-kappa B p65 subunit and c-Rel. In addition, NF-kappa B2 was also found to contain p50 subunit of NF-kappa B. The binding of three types of NF-kappa B proteins to HIV NF-kappa B motif was effectively inhibited by other NF-kappa B motifs, whose 3' half-site nucleotide sequences are T/A-T-T/C-CC (HIV, interleukin-6, interferon (INF)-beta, H2-Kb, I-E alpha d, and TNF-alpha 2 (nucleotide position -510)) and much less effectively by NF-kappa B motifs with 3' half-site sequences of TGCCC (TNF-alpha 3, nucleotide position -610), ATCTC (G CSF), TATTC (Fc gamma R), or TCCTT (TNF-alpha 1, nucleotide position -850). Our data also suggested that NF-kappa B1 and -kappa B2 which contain p50 subunit of NF-kappa B bind with the higher preference for NF-kappa B motif of H2-Kb gene promoter than that of INF-beta, whereas NF-kappa B3 which does not contain p50 subunit appears to preferentially bind to NF-kappa B sites of IFN-beta. PMID- 8366098 TI - Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA. A potential disease mechanism. AB - A patient with a mitochondrial myopathy and biochemically proven profound complex I deficiency has a new mutation in mtDNA. This A-to-G transition at position 3302, involving the aminoacyl stem of tRNA(Leu(UUR)), is associated with abnormal mitochondrial RNA processing. Northern analysis demonstrates marked accumulation of a polycistronic RNA precursor containing sequence for 16 S rRNA, tRNA(Leu(UUR)), and ND1. Comparison of skeletal muscle and skin fibroblasts suggests that the processing error may be quantitatively less severe in this tissue, and biochemical analysis shows that fibroblasts do not express a biochemical defect despite containing the mutation. Important qualitative differences in the processing of this RNA precursor were found when comparing muscle and skin fibroblasts. In muscle, processing appears to occur first at the 5'-end of the tRNA, generating 16 S rRNA plus a tRNA + ND1 intermediate. In fibroblasts, processing occurs at the 3'-end of the tRNA, generating a 16 S rRNA + tRNA intermediate. We suggest that the mutation at position 3302 induces abnormal mitochondrial RNA processing that is linked to the biochemical defect (profound loss of complex I activity), either by qualitative or quantitative abnormalities in the ND1 message. The restriction to skeletal muscle of both the processing error and the biochemical defect suggests that the observed tissue differences in RNA processing play a protective role in skin fibroblasts. PMID- 8366099 TI - Nucleosome interactions with a human Alu element. Transcriptional repression and effects of template methylation. AB - Alu interspersed repetitive elements possess internal RNA polymerase III promoters which are strongly transcribed in vitro, yet these elements are nearly silent in somatic cells. To examine whether repression by chromatin proteins could contribute to the low level of Alu expression, a conserved Alu element from the fourth intron of the human alpha-fetoprotein gene was reconstituted with purified octamer or tetramer particles. Analysis of reconstitutes revealed that this Alu element directed translational and rotational positioning of octamers as well as tetramers. In vitro transcription experiments with reconstituted templates demonstrated that RNA polymerase III-dependent transcription of the Alu element was profoundly repressed by positioned octamer particles. Furthermore, complete CpG methylation of this template enhanced the capacity of tetramers to repress transcription. PMID- 8366100 TI - Purification and characterization of recombinant Bet v I, the major birch pollen allergen. Immunological equivalence to natural Bet v I. AB - Pollen from trees of the order Fagales (e.g. birch, alder, hazel, oak, and hornbeam) are a major cause of Type I allergies observed in early spring. Previously, we reported the cloning and sequencing of Bet v I, the major birch pollen allergen, which showed high sequence similarities to a family of plant pathogen-activated genes (Breiteneder, H., Pettenburger, K., Bito, A., Valenta, R., Kraft, D., Rumpold, H., Scheiner, O., and Breitenbach, M. (1989) EMBO J. 8, 1935-1938). Here, we present the results on the expression, purification, and characterization of recombinant Bet v I produced in Escherichia coli as fusion and non-fusion protein, respectively. The purified recombinant proteins were analyzed to verify purity and structural integrity, and their immunological properties were compared to those of Bet v I isolated from birch pollen (natural Bet v I). Immunoblot analyses showed that the recombinant proteins are specifically recognized by monoclonal antibodies raised against natural Bet v I as well as by IgE from birch pollen-allergic patients. However, enzyme-linked immunosorbent assays revealed a decreased IgE-binding activity of the recombinant fusion Bet v I compared to the non-fusion and natural Bet v I proteins, which probably results from conformational changes due to the fusion tail. Recombinant non-fusion Bet v I was equivalent to natural Bet v I with respect to IgE-binding properties, the ability to induce in vitro proliferation of allergen-specific T cell clones, and the ability to release histamine from basophils derived from birch pollen-allergic patients. PMID- 8366102 TI - Somatic mutations in c-myc intron I cluster in discrete domains that define protein binding sequences. AB - The activated c-myc allele in Burkitt's lymphoma tumor cells is associated with a clustering of somatic mutations within intron I near the exon I boundary. We have identified several discrete protein binding sites within this region of c-myc intron I designated as myc intron factor-1 (MIF-1), MIF-2, and MIF-3. In addition to our previous characterization of a 20-nucleotide binding site for MIF-1, we now have identified adjacent 20-nucleotide and 34-nucleotide binding sites for MIF-2 and MIF-3, respectively. All three elements are protected from exonuclease digestion by nuclear protein extracts, and each gives rise to a distinct migration pattern on mobility shift assays. In addition, MIF-1, 2, and 3 share a 5-nucleotide (TTATG) internal sequence, which may account for cross-competition of these binding sites in the exonuclease protection experiment. Deletion mutant analyses showed that selective removal of the MIF-3 binding site alone was sufficient to enhance chloramphenicol acetyltransferase reporter activity similar to that observed with larger deletions of myc intron I. We have demonstrated that somatic mutations in activated c-myc alleles are frequently clustered in discrete domains that define protein recognition sequences. PMID- 8366101 TI - Identification of a new cAMP response element-binding factor by southwestern blotting. AB - We have identified in mammalian cells a novel cyclic AMP response element (CRE) binding protein of molecular mass 47 kDa. This protein was not recognized by either the CREB-327/341 or c-Jun antisera, and its tissue distribution did not overlap with those of the CREB and Jun families. For example, hepatoma and placental tissue did not contain the 47-kDa DNA-binding protein, but did contain the CREB isoforms. On the other hand, S49 lymphoma cells contained a high level of the 47-kDa DNA-binding protein but did not contain a 47-kDa Jun-related protein which was found in normal liver and hepatoma. This new 47-kDa factor bound to the CRE in the dephosphorylated form, and phosphorylation of the protein by the catalytic subunit of protein kinase A completely abolished its DNA-binding activity. The isoforms of the CREB-327/341 family, on the other hand, bound to DNA in the phosphorylated form, and alkaline phosphatase treatment reduced significantly their interaction with CRE sequence. This reverse effect of phosphorylation/dephosphorylation on the DNA-binding property of this new 47-kDa protein in particular distinguishes it from other known CREB factors and suggests that the protein might play a unique role in the regulation of cAMP-mediated transcription. PMID- 8366103 TI - Interaction between band 3 and ankyrin begins in early compartments of the secretory pathway and is essential for band 3 processing. AB - In many cell types, membrane proteins are specifically segregated to particular areas of the cell surface. It is known that this segregation is stabilized by anchorage proteins which interact with the cytoskeleton. However, the mechanism by which the interactions with anchorage proteins occur, as well as whether they may also play a role in the process of sorting, is not known. Using differentiated murine erythroleukemic cells, we have investigated the association between band 3 (a major transmembrane anion exchanger), and ankyrin (a cytoplasmic protein that links band 3 to the cytoskeleton). Our data demonstrate that the association between band 3 and ankyrin occurs in the endoplasmic reticulum or the first Golgi compartment. These data support a model in which the band 3-ankyrin complex is inserted as a "cassette" at the plasma membrane into the cytoskeletal network. Biosynthetic studies on cotransfected 293 cells with cDNAs encoding band 3 and the band 3 binding fragment of ankyrin (AnK-90), suggest that ankyrin is not only responsible for the anchorage of band 3 to the cytoskeleton but is also involved in the exit of band 3 out of the endoplasmic reticulum. PMID- 8366104 TI - A plant glutamate decarboxylase containing a calmodulin binding domain. Cloning, sequence, and functional analysis. AB - Molecular procedures have been applied to isolate plant calmodulin-binding proteins. A petunia cDNA expression library was screened with 35S-labeled recombinant calmodulin as a probe, and a cDNA coding for a Ca(2+)-dependent calmodulin-binding protein was isolated. The deduced amino acid sequence of the petunia protein (500 amino acid residues, 58 kDa) has 67% overall amino acid sequence similarity to glutamate decarboxylase (GAD) from Escherichia coli (466 amino acid residues, 53 kDa). The recombinant protein expressed in E. coli cells displays GAD activity, i.e. catalyzes the conversion of glutamic acid to gamma aminobutyric acid and binds calmodulin, whereas E. coli GAD does not bind calmodulin. The calmodulin binding domain in the petunia GAD was mapped by binding truncated forms of GAD immobilized on nitrocellulose membranes to recombinant petunia 35S-calmodulin as well as to biotinylated bovine calmodulin and by binding truncated forms of GAD to calmodulin-Sepharose columns. The calmodulin binding domain in petunia GAD is part of a carboxyl end extension that is not present in E. coli GAD. Polyclonal antibodies raised against the recombinant petunia GAD detect a single protein band from plant extracts of gel mobility identical to that of the recombinant GAD. Moreover, the plant protein binds calmodulin in vitro. This is the first report of the isolation of a GAD gene from plants and of a calmodulin-binding GAD from any organism. Our results raise the possibility that intracellular Ca2+ signals via calmodulin are involved in the regulation of gamma-aminobutyric acid synthesis in plants. PMID- 8366105 TI - Post-translational folding of influenza hemagglutinin in isolated endoplasmic reticulum-derived microsomes. AB - The folding of influenza hemagglutinin was analyzed after in vitro translation and translocation into dog pancreas microsomes. Ectodomain folding of this membrane glycoprotein involves the formation of six intrachain disulfide bonds. After translation under reducing conditions, the folding process was initiated by the addition of oxidized glutathione or diamide. For correct folding a reduction oxidation potential of -310 to -210 mV had to be reached in the bulk solution. At lower values, or after addition of other oxidants such as NAD or NADP, no HA disulfides formed. At more oxidizing values interchain disulfide-cross-linked aggregates were generated. Judging by their electrophoretic gel mobility and immunoreactivity, the folding intermediates observed in microsomes were indistinguishable from those previously seen in the endoplasmic reticulum of live cells. The kinetics of folding was also similar, but the efficiency being 43% was somewhat lower. The folding process was dependent on lumenal factors within the rough endoplasmic reticulum vesicles and also on some macromolecular component(s) present in the reticulocyte lysate. The results showed that dog pancreas microsomes provide a useful system for protein folding studies. PMID- 8366106 TI - Ring finger motif of Arabidopsis thaliana COP1 defines a new class of zinc binding domain. AB - The COP1 gene of Arabidopsis thaliana encodes a protein mediating the switch between the two developmental pathways utilized in light and darkness. A cysteine rich motif identified the COP1 protein as a member of a group of regulatory proteins which share the amino acid motif Cys-X-X-Cys-loop I-Cys-X-His-X-X-Cys-X X-Cys-loop II-Cys-X-X-Cys (ring finger). Although this new class of cysteine-rich motifs has been proposed to bind metal ions, no direct evidence supporting this has been presented. By analyzing the COP1 protein expressed in Escherichia coli, we demonstrate here that each COP1 molecule can bind up to two zinc atoms. The two zinc ions are bound with different affinities. One is tightly bound and resistant to urea and EDTA, whereas the other one is labile under those conditions. It is further shown that deletion of the ring finger motif abolishes the metal-binding capacity of COP1. We conclude that the ring finger motif constitutes a zinc-coordinating element distinct from previously characterized zinc-binding domains. PMID- 8366107 TI - Characterization of the signal transduction pathways and cis-acting DNA sequence responsible for the transcriptional induction during growth and development of the lysosomal alpha-mannosidase gene in Dictyostelium discoideum. AB - The lysosomal alpha-mannosidase gene in Dictyostelium discoideum is representative of a small group of genes that are expressed under two different conditions: 1) immediately upon removal of the bacterial food source from exponentially growing cells at < 5 x 10(5) cells/ml (which also initiates the developmental cycle), and 2) when the concentration of a secreted glycoprotein termed the prestarvation response factor (PSF) reaches a critical threshold in cultures growing at densities > 5 x 10(5) cells/ml. In this report we show that transcription of the alpha-mannosidase gene induced by starvation did not require protein synthesis in axenic wild-type strains, whereas protein synthesis was required for the transcriptional induction observed in response to PSF. Northern blot analysis was also done using mRNA from G alpha 1 and G alpha 2 gene disruption mutants. These genes encode subunits of heterotrimeric G proteins found at the cell surface in growing cells and cells early in development. The pattern of alpha-mannosidase gene expression was normal in these mutants as well as in mutants unable to produce the secreted glycoprotein conditioned medium factor or the cAMP receptor-1 protein. These genes have been shown to regulate the expression of many genes during early development. Promoter analysis studies identified a 145-base pair sequence element containing a TTG box which was required for alpha-mannosidase transcriptional induction under both starvation conditions and in response to PSF. The TTG box identified is an important regulatory element in the promoter of another prestarvation response gene, the discoidin I gamma gene. A ts mutant was found to misregulate the expression of both discoidin I and alpha-mannosidase expression at restrictive temperatures. Taken together these results suggest that the prestarvation response genes may be coordinately regulated possibly through the TTG box. PMID- 8366108 TI - Crystals of a hammerhead ribozyme. AB - Hammerhead ribozyme-inhibitor complexes consisting of an RNA "enzyme" strand and a DNA "inhibitor" strand have been crystallized in four different crystal forms. The crystal form that is most attractive for structure determination diffracts to approximately 3.2 A resolution; it is trigonal, space group P3(1)21 or enantiomorph, a = 92.5 A, c = 185.0 A. PMID- 8366109 TI - Ribosomal protein L32 of Saccharomyces cerevisiae regulates both splicing and translation of its own transcript. AB - Ribosomal protein L32 of Saccharomyces cerevisiae regulates the splicing of its own transcript (1, 2) apparently by interacting with a structure composed largely of the 5' exon. However, even in strains overproducing L32 mRNA, e.g. from a cDNA copy of the gene, little accumulation of L32 is observed after a brief pulse label. When the 5' leader of the RPL32 mRNA is replaced by an exogenous leader, the amount of pulse-labeled L32 increases severalfold, suggesting that L32 regulates the translation of its own mRNA, acting through sequences in the 5' region. This conclusion was confirmed by the observation that in cells carrying a chimeric gene in which the L32 leader is fused to LacZ coding sequences, the presence of a second gene that overexpresses L32 itself reduces the level of beta galactosidase by 50%, in spite of a doubling of L32-lacZ fusion mRNA, presumably due to stabilization of the message. Mutations within the 5' leader that abolish the regulation of splicing also abolish the regulation of translation, suggesting that the regulation of translation by L32 involves a structure similar to that proposed for the regulation of splicing. In cells overproducing L32-mRNA about half the excess mRNA was found in ribonucleoproteins of < 25 S, unassociated with ribosomal particles. Much of the rest was found in ribonucleoproteins of 80-120 S. PMID- 8366110 TI - Synthesis of phosphorylated oligosaccharides in lysozyme is enhanced by fusion to cathepsin D. AB - Chinese hamster ovary cells transfected with human lysozyme cDNA encoding Asn instead of Gly22 synthesize a mutant lysozyme, [Asn22]lysozyme, with about 60% of the molecules bearing carbohydrate. This carbohydrate is predominantly of the complex type and contains a varied number of lactosamine repeats. In this study we show that the glycosylation of [Asn22] lysozyme fused to human cathepsin D is altered relative to [Asn22]lysozyme alone. The fusion protein is synthesized as a 66-kDa precursor that is cleaved to enzymatically active and antigenically positive cathepsin D and lysozyme. As compared with [Asn22]lysozyme the lysozyme moiety of the fusion protein shows an increased N-glycosylation and a decreased synthesis of lactosamine repeats. Cleavage of the precursor with cathepsin L has revealed that the lysozyme portion of the secreted fusion protein bears a complex type carbohydrate. The intracellularly released lysozyme portion of the fusion protein contains trimmed oligosaccharides. In the presence of NH4Cl the lysosomal targeting of the fusion protein is inhibited. The secreted protein is then enriched in molecules bearing phosphorylated high mannose oligosaccharides in their lysozyme moiety. Our results indicate that carbohydrate processing in [Asn22]lysozyme, including the synthesis of mannose 6-phosphate residues and of lactosamine repeats, is altered by the attached cathepsin D. The phosphorylation of the carbohydrate on the lysozyme portion results in a very efficient lysosomal targeting of the concerned fusion protein molecules. PMID- 8366111 TI - Identification of enhancers in the 5'-flanking region of the rabbit surfactant protein A (SP-A) gene and characterization of their binding proteins. AB - The gene encoding surfactant protein A (SP-A) is expressed in type II pneumonocytes and is developmentally and hormonally regulated in fetal lung. In the present study, rabbit lung nuclear proteins were found to bind to two genomic elements within the 5'-flanking region of the rabbit SP-A gene, termed distal binding element (DBE; -986 to -977 base pairs) and proximal binding element (PBE; -87 to -70 base pairs). Binding activity was enriched in type II pneumonocytes as compared with whole lung tissue. Although binding activity was undetectable in nuclear proteins from rabbit liver and kidney, low levels of binding activity were detected in nuclear proteins from cardiac and skeletal muscle. DNase I footprinting indicated that lung nuclear proteins protected the palindromic sequence CCCACGTGGG in the DBE. The underlined core sequence is an E box motif; a similar sequence (CCCTCGTG) is present within the PBE. Both elements competed for binding to the same size species of nuclear proteins of M(r) approximately 69,000, 45,000, and 22,000. In type II cells transfected with fusion genes containing SP-A 5'-flanking DNA linked to the human growth hormone structural gene, mutagenesis of the DBE or PBE resulted in a marked reduction of basal and cyclic AMP-stimulated fusion gene expression. These findings suggest that the DBE and PBE act as enhancers that interact with the same or related trans-acting proteins and serve an important role in type II cell-specific, cyclic AMP mediated regulation of SP-A gene expression. PMID- 8366112 TI - Expression, purification, and kinetic characterization of recombinant human adenylosuccinate lyase. AB - Adenylosuccinate adenosine 5'-monophosphate lyase (EC 4.3.2.2; ASL) catalyzes two distinct reactions in adenosine 5'-monophosphate (AMP) biosynthesis. A S413P mutation in ASL segregates with mental retardation in an affected family (Stone, R. L., Aimi, J., Barshop, B. A., Jaeken, J., Van den Berghe, G., Zalkin, H., and Dixon, J. E. (1992) Nature Genet. 1, 59-63). ASL and S413P ASL have been expressed, purified, and kinetically characterized. Lowering the Escherichia coli growth temperature to 25 degrees C and the concentration of inducer, isopropyl-1 thio-beta,D-galactopyranoside, to 40 microM was necessary for synthesis of soluble, tetrameric enzymes. The recombinant enzymes were purified to homogeneity using anion exchange chromatography followed by chromatography on Blue 2A Sepharose. At pH 7.0 and 25 degrees C, the kcat for cleavage of 5-amino-4 imidazole-N-succinocarboxamide ribotide (SAI-CAR) by ASL was 90 s-1 with a Km of 2.35 microM. The kcat for adenylosuccinate (SAMP) cleavage was 97 s-1 with a Km of 1.79 microM. The catalytic mechanism involved one general base catalyst (pK alpha = 6.4) and one general acid catalyst (pK alpha = 7.5). ASL follows an ordered uni-bi reaction mechanism with fumarate released first. 5-Amino-4 imidazolecarboxamide ribotide (AICAR) and AMP were competitive with SAICAR and SAMP (Ki[AICAR] = 11.3 microM; Ki[AMP] = 9.2 microM), whereas fumarate inhibited noncompetitively (Kii = 2.3 mM, Kis = 2.8 mM). The competitive inhibition by AICAR and AMP suggests a single active site that binds both SAICAR and SAMP. The kinetic constants at pH 7.0, 25 degrees C and the kcat/Km versus pH profiles for ASL and S413P ASL were very similar. These results are consistent with S413P being a structural rather than a catalytic defect. PMID- 8366113 TI - Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. AB - Amphoterin is a heparin-binding protein that is developmentally regulated in brain and functionally involved in neurite outgrowth. Unexpectedly, amphoterin has a high mobility group 1 (HMG1)-type sequence. In the present study we have expressed amphoterin cDNA in a baculovirus vector and produced antibodies against the recombinant protein and several synthetic peptides. It was found that the amphoterin cDNA encodes the 30-kDa form of the protein isolated from tissues, whereas the co-purifying 28- and 29-kDa proteins (p28 and p29) have closely related but distinct primary structures. Partial amino acid sequencing shows several local changes in the sequences of p28 and p29 compared with amphoterin, suggesting the occurrence of a multigene family that encodes at least three different HMG1-type sequences in the rat. Studies using the probes that discern amphoterin from the other HMG1-type proteins indicate a high level expression in various transformed cell lines. Immunostaining of cells with the amphoterin specific antibodies indicates a cytoplasmic localization that becomes remarkably enriched at the leading edges in spreading and motile cells. An extracellular localization is suggested by immunostaining of nonpermeabilized cells and by a plasminogen-dependent degradation of amphoterin in the substratum-attached material of cells. Tissue-derived and recombinant amphoterins strongly enhance the rate of plasminogen activation and promote the generation of surface-bound plasmin both by tissue-type and urokinase-type plasminogen activators. The results suggest an extracellular function for amphoterin in the leading edge of various invasive cells. PMID- 8366114 TI - Proliferation of intracellular structures upon overexpression of the PMA2 ATPase in Saccharomyces cerevisiae. AB - The PMA2 gene is a presumed isogene of the PMA1 gene, encoding the major yeast plasma membrane H(+)-ATPase. When controlled by its own promoter, PMA2 in multiple copies does not complement a deficient PMA1 gene. Under the control of the PMA1 promoter, however, and expressed on a centromeric plasmid in yeast strains specially designed for stable expression, the PMA2 gene replaces the PMA1 gene to some extent, allowing growth on standard medium but not on acidic media. Plasma membranes of cells expressing only the PMA2 enzyme display low ATPase activity correlating with low amounts of PMA2 protein. This low activity is maintained throughout growth and does not increase when overexpression is favored by increased gene dosage. Immunoelectron microscopy reveals a dramatic proliferation of intracellular structures (probably endoplasmic reticulum) in which overexpressed PMA2 protein accumulates. Overexpression of PMA1 ATPase causes a similar phenomenon, but quantitative effects are lower compared to PMA2. These results indicate that the PMA2 gene encodes a functional plasma membrane H(+)-ATPase and suggest a specific control of the intracellular traffic of plasma membrane ATPase. PMID- 8366115 TI - Gap junction communication modulates [Ca2+]i oscillations and enzyme secretion in pancreatic acini. AB - Global (all cells in an acinus) and focal (1-2 out of 10-15 cells) stimulation of pancreatic acini with bombesin or t-butyloxycarbonyl-Tyr(SO3)-Nle-Gly-Tyr-Asp-2 phenylethyl ester (CCKJ) together with modulation of gap junction (GJ) permeability by octanol and NO2- was used to study the role of GJ permeability in controlling [Ca2+]i oscillations and enzyme secretion. GJ permeability was quantitated by measuring fluorescence recovery after photobleaching. Octanol at 0.5 mM markedly reduced, whereas 15 mM NO2- increased GJ permeability. Focal application of bombesin caused synchronized oscillations in the entire acinus, whereas global stimulation resulted in asynchronous oscillations. Increasing GJ permeability with NO2- had no effect on bombesin-evoked [Ca2+]i oscillations. Octanol inhibited ongoing oscillations evoked by focal or global bombesin stimulation. However, when GJ were blocked prior to stimulation, subsequent global stimulation with bombesin induced long-lasting oscillations in all cells. Re-establishing GJ communication for as little as 37.5 s conferred GJ dependence on the order and time of [Ca2+]i spiking evoked by global bombesin stimulation. Focal and global stimulation with CCKJ gave different patterns of [Ca2+]i oscillations. However, in contrast to bombesin, inhibition of GJ with octanol had no effect on oscillations induced by global CCKJ stimulation. Increasing GJ permeability with NO2- synchronized CCKJ-stimulated oscillations by equalizing the amplitude and increasing the frequency in all cells within an acinus. These observations suggest that amplitude and frequency of [Ca2+]i oscillations can be regulated independently of each other, and that GJ permeable molecules modulate the frequency of [Ca2]i oscillation in an agonist-specific manner. Regardless of the agonist, increasing the frequency of oscillations by modulation of GJ permeability correlated with an increased enzyme secretion. PMID- 8366116 TI - Yeast mitochondrial RNase P. Sequence of the RPM2 gene and demonstration that its product is a protein subunit of the enzyme. AB - We report here the sequence of the RPM2 gene which codes for the 105-kDa protein previously purified from the mitochondria of Saccharomyces cerevisiae and shown by genetic techniques to be required for mitochondrial RNase P activity. The sequence predicts a primary translation product of 1202 residues with a molecular mass of 139 kDa and no obvious sequence similarity to any known protein in the data bases. There are 122 amino-terminal amino acids predicted by the gene that are not found in the purified protein, some of which may play a role in mitochondrial targeting of the protein. Antibodies raised against a trpE-105-kDa fusion protein recognize a 105-kDa protein in wild-type cells but not in cells carrying a disruption of the RMP2 gene. Immune, but not preimmune serum, immunoprecipitates the RNase P RNA and the mitochondrial RNase P activity. Thus, the 105-kDa protein forms a complex with RNase P RNA and is required for RNase P activity as predicted for a bona fide subunit of the enzyme. PMID- 8366117 TI - Tandem SH2 domains of ZAP-70 bind to T cell antigen receptor zeta and CD3 epsilon from activated Jurkat T cells. AB - A proximal and critical biochemical event upon T cell antigen receptor (TCR) stimulation is the activation of a protein tyrosine kinase (PTK) pathway. ZAP-70, a PTK of the p72syk family, associates with phosphorylated TCR subunits upon TCR stimulation. Here we report that the tandem SH2 domains of ZAP-70, expressed as a fusion protein, bind to tyrosine-phosphorylated CD3 epsilon and TCR zeta from activated Jurkat T cell lysates. The single N- and C-terminal SH2 domains of ZAP 70, expressed separately, do not bind these TCR subunits. In comparison to fusion proteins containing SH2 domains from other proteins, the tandem SH2 domains of ZAP-70 demonstrate a remarkably restricted repertoire of protein binding, binding only TCR zeta and CD3 epsilon. ZAP-70 is also recovered in the binding assay, but this is likely to be a consequence of its interaction with multiple SH2 binding sites on the zeta-zeta and CD3 epsilon-containing dimers. PMID- 8366118 TI - The role of the carboxyl-terminal tail in human O6-methylguanine DNA methyltransferase substrate specificity and temperature sensitivity. AB - The human O6-methylguanine DNA methyltransferase (MGMT) repairs O6-methylguanine (O6-MG) in DNA at a much lower rate than the Escherichia coli Ada protein, and only MGMT repairs the altered base, O6-benzylguanine (O6-BG). The diversity in DNA repair properties between MGMT and Ada may be a result of divergent amino acid sequences outside their common proline-cysteine-histidine-arginine-valine (PCHRV) acceptor site. One notable sequence difference is an MGMT 28-amino acid carboxyl-terminal tail which is highly conserved among all mammalian alkyltransferases. The role of this tail sequence in substrate specificity was assessed by expressing full-length MGMT and Ada proteins, and mutant MGMT proteins lacking either 10 or 28 amino acids from the carboxyl terminus, as GST fusion proteins in alkyltransferase-deficient E. coli cells, and comparing rates of repair of O6-MG containing DNA and O6-BG by these fusion proteins at 4 degrees C and 37 degrees C. The MGMT carboxyl-terminal tail was not required for repair of O6-MG in DNA at 37 degrees C although the deletion of this tail sequence reversibly inhibited the ability of MGMT to repair O6-MG in DNA at 4 degrees C. Therefore, the absence of this region affects the ability of the protein to repair O6-MG in DNA at lower temperatures. Furthermore, removal of the tail sequence from MGMT decreased the rate of O6-BG repair 5-fold. We conclude that the 28-amino acid carboxyl-terminal MGMT tail, while not required for activity, modulates the rate of MGMT repair at reduced temperatures and plays a role in substrate specificity. PMID- 8366119 TI - Regulation of selective protein degradation in the endoplasmic reticulum by redox potential. AB - Recent studies show that the endoplasmic reticulum (ER) contains proteases, but it is not understood how these enzymes are regulated. In this report we study the selective ER degradation of the subunits (alpha beta gamma delta epsilon zeta) of the T-cell antigen receptor (TCR). When analyzed in vivo, unassembled subunits of the TCR fail to reach the Golgi apparatus and show a differential sensitivity to degradation after synthesis. The alpha, beta, and delta subunits are degraded rapidly, while gamma, epsilon, and zeta are stable. To study the regulation of proteolysis in more detail, beta, gamma, delta, and epsilon subunits were expressed alone in fibroblasts and their selective degradation analyzed in vitro. The beta and delta chains were degraded in the complete absence of vesicular transport, indicating their degradation in the ER membrane compartment. Proteolysis was unaffected by GTP gamma S (guanosine 5'-O-(thiotriphosphate)), EDTA, or depletion of ATP. The gamma and epsilon subunits were stable under the same in vitro conditions, indicating that the assay reconstituted selective protein degradation within the ER. Furthermore, the results showed that the gamma and epsilon subunits did not escape degradation by being transported from the ER to pre-Golgi, or cis-Golgi, membrane compartments. Structural determinants of ER degradation contained within the membrane anchor of the TCR beta subunit were only active in permeabilized cells when reducing agents were added to the assay. Surprisingly, reducing conditions disrupted the regulation of ER proteolysis and induced rapid ER degradation of the stable CD3 gamma subunit and of a control interleukin 2 receptor chimera. Taken together, the results indicated that the ER membrane compartment regulates the selective degradation of newly synthesized proteins. Importantly, the stability of proteins retained in the ER was highly sensitive to redox conditions. It is possible that the redox buffer within the ER lumen may regulate ER protein degradation in vivo. PMID- 8366120 TI - Identification of the cysteine residue in apolipoprotein(a) that mediates extracellular coupling with apolipoprotein B-100. AB - We have utilized a recombinant expression system in order to study the assembly of lipoprotein(a) (Lp(a)) particles. Using a 17-kringle recombinant form of apolipoprotein(a) (apo(a)) to transiently transfect human hepatoma cells, we could not detect recombinant Lp(a) (r-Lp(a)) particles intracellularly, by analysis of postnuclear lysates. However, covalent r-Lp(a) complexes were observed in the transfected cell supernatants. Upon addition of [35S]Cys-labeled human embryonic kidney cell supernatants transfected with 9-kringle or 17-kringle recombinant apo(a) (r-apo(a)) variants to human plasma, covalent r-Lp(a) complexes were observed, which could be immunoprecipitated using antibodies specific for either apo(a) or apolipoprotein B-100 (apoB-100); r-Lp(a) complexes containing the 17-kringle r-apo(a) were shown to be in the 1.063 g/ml < d < 1.20 g/ml range by density gradient ultracentrifugation analysis. Complexes containing the 17-kringle r-apo(a) formed rapidly within 20 min, with a slow increase observed up to 90 min. Addition of increasing amounts of plasma, as well as increasing amounts of isolated human low density lipoprotein to cell culture supernatants containing [35S]Cys-labeled 17-kringle r-apo(a) led to enhanced r Lp(a) complex formation. Blocking of free sulfhydryls in apo(a) with N ethylmaleimide resulted in inhibition of r-Lp(a) complex formation in plasma, verifying the role of free sulfhydryls in Lp(a) particle assembly. Using site directed mutagenesis, we demonstrated that Cys4057 in apo(a) is involved in disulfide linkage with apoB-100 in Lp(a) particles. PMID- 8366121 TI - Activation of an S6 kinase from human placenta by autophosphorylation. AB - A number of protein kinases have been shown to undergo autophosphorylation, but few have demonstrated a coordinate increase or decrease in enzymatic activity as a result. Described here is a novel S6 kinase isolated from human placenta which autoactivates through autophosphorylation in vitro. This S6/H4 kinase, purified in an inactive state, exhibited a molecular mass of 60 kDa as estimated by SDS polyacrylamide gel electrophoresis. The 60-kDa protein underwent autophosphorylation, was labeled by 8-azido-[alpha-32P]ATP, and reacted with an antibody to the conserved APE domain of the cAMP-dependent protein kinase. The protein did not cochromatograph with p70 S6 kinase and did not cross-react with an anti-p70 kinase antibody. The synthetic peptide S6-21, histone H4, and myelin basic protein were phosphorylated by the purified S6/H4 kinase. Mild digestion of the inactive S6/H4 kinase with trypsin generated a 40-kDa fragment, as determined by SDS-polyacrylamide gel electrophoresis. The trypsin treatment was necessary, but not sufficient, to fully activate the kinase. Subsequent incubation of the trypsin-treated S6 kinase with MgATP resulted in the rapid autophosphorylation of the 40-kDa fragment along with a coordinate increase in kinase activity. The autophosphorylation of the 40-kDa protein was positively correlated with MgATP incubation time and an increase in activity toward the S6-21 peptide, histone H4, and myelin basic protein. Taken together, these data support the hypothesis that this previously uncharacterized S6 kinase belongs to a unique family of protein kinases which utilize autophosphorylation as part of their in vivo activation mechanism. PMID- 8366122 TI - Synthesis and stability of reaction center polypeptides and implications for reaction center assembly in Rhodobacter sphaeroides. AB - The synthesis and stability of the H and M polypeptide subunits of the photosynthetic reaction center of Rhodobacter sphaeroides were examined. In wild type cells, low levels of both M and H were found to be synthesized under aerobic growth conditions, with a 20-fold induction in their synthesis under anaerobic dark growth conditions. Neither M nor H was stable in aerobic cells, but in anaerobic-dark grown cells stability increased dramatically with the t1/2 going from 4-6 min to values estimated in excess of 4 h. In the H-deficient mutant PUHA1, the synthesis and membrane partitioning of the M subunit were unaffected by the absence of the H subunit but there was a significant decrease in M polypeptide stability in the membranes of PUHA1 relative to wild-type cells. The stability of all or part of the M population in PUHA1 could be restored by providing an H-encoding plasmid in trans. It was also determined that the presence of bacteriochlorophyll in fully aerobic cells had a direct, positive effect on M and H stability, utilizing the oxygen-regulatory mutant strain T1a. Implications for the role of the H subunit and putative assembly factors in reaction center assembly are discussed. PMID- 8366123 TI - Signaling events initiated by transforming growth factor-beta 1 that require Gi alpha 1. AB - Transforming growth factor-beta 1 (TGF-beta 1) initiates a series of signaling events leading to diverse cell type-specific effects on proliferation and morphology. The multiple effects of TGF-beta 1 are not due to selective expression of receptor subtypes, but rather probably reflect cell-specific expression of downstream components of the particular signaling system. To address this possibility and to identify specific signaling pathways activated by TGF-beta 1, we attempted to restore cell responsiveness to the cytokine by introducing various intracellular signal transducers in NIH-3T3 fibroblasts, a cell line that is minimally responsive to TGF-beta 1. In NIH-3T3 fibroblasts stably transfected with Gi alpha 1 cDNA, TGF-beta 1 induced a reversible morphological transformation that was identical to the effect of this cytokine in indicator cells such as AKR-2B fibroblasts. Gi alpha 1 transfectants also exhibited mitogenic hyperresponsiveness to TGF-beta 1. TGF-beta 1 does not elicit these responses in control nontransfected fibroblasts or cells transfected with the guanine nucleotide-binding protein Go alpha 1. The response to TGF-beta 1 in Gi alpha 1 transfectants is blocked by pertussis toxin and is lost in Gi alpha 1 transfectants that have spontaneously reverted and no longer express Gi alpha 1. These data indicate that the expression of the guanine nucleotide-binding protein Gi alpha 1, normally absent in these cells, confers cell sensitivity to TGF-beta 1. PMID- 8366124 TI - UDP-N-acetylglucosamine acyltransferase of Escherichia coli. The first step of endotoxin biosynthesis is thermodynamically unfavorable. AB - UDP-N-acetylglucosamine acyltransferase of Escherichia coli catalyzes the reaction, UDP-GlcNAc + R-3-hydroxymyristoyl-ACP--> UDP-3-O-(R-3-hydroxymyristoyl) GlcNAc + ACP. Using Matrex Gel Green A and heparin-agarose, we have purified the enzyme to near homogeneity from a strain that overproduces it 474-fold. The subunit molecular mass determined by SDS-gel electrophoresis is approximately 30 kDa, consistent with results of previous radiolabeling experiments in mini-cells. The amino-terminal sequence (Met-Ile-Asp-Lys-Ser-Ala-Phe-Val-His-Pro) and the amino acid composition of the purified protein are consistent with DNA sequencing (Coleman, J., and Raetz, C. R. H. (1988) J. Bacteriol. 170, 1268-1274). At saturating concentrations of the second substrate, the apparent Km values for UDP GlcNAc and R-3-hydroxymyristoyl-ACP are 99 and 1.6 microM, respectively. There is an absolute requirement for the R-3-hydroxy moiety of the fatty acyl-ACP substrate; myristoyl-ACP binds effectively (IC50 = 2 microM) but is inactive (< 0.01%) as an alternate substrate. The most remarkable feature of the reaction is its unfavorable equilibrium constant, Keq approximately equal to 0.01, which is not predicted by model S-->O acyl transfer reactions. Thus, although UDP-GlcNAc acyltransferase catalyzes the first unique step of lipid A biosynthesis, it is the second enzyme (the deacetylase) that commits the substrates to this pathway. The specific activity of the deacetylase is elevated approximately 5-fold when lipid A synthesis is inhibited. PMID- 8366125 TI - The firA gene of Escherichia coli encodes UDP-3-O-(R-3-hydroxymyristoyl) glucosamine N-acyltransferase. The third step of endotoxin biosynthesis. AB - The possibility that the firA gene of Escherichia coli (Dicker, I. B., and Seetharam, S. (1991) Mol. Microbiol. 6, 817-823) might function in lipid A biosynthesis was examined based on its homology to the lpxA gene, which encodes UDP-N-acetylglucosamine O-acyl-transferase, the first enzyme in lipid A formation. Extracts of a temperature-sensitive firA mutant, RL-25, were assayed for their ability to acylate UDP-GlcNAc, using a coupled assay. The results suggested that extracts of RL-25 might be defective in the third enzyme of this pathway, the UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase. Living cells of RL-25 also displayed a 5-fold decreased rate of lipid A biosynthesis at the nonpermissive temperature as judged by a 32Pi incorporation assay. In order to examine N-acyltransferase activity directly, the substrate [alpha-32P]UDP-3-O (R-3-hydroxymyristoyl)-GlcN was synthesized enzymatically. N-Acyltransferase specific activity in RL-25 extracts was reduced to less than 10% of wild-type. When the wild-type firA gene was cloned into a T7-based expression vector, N acyltransferase specific activity increased almost 360-fold relative to wild-type extracts, demonstrating that firA is the structural gene for the enzyme. The N acyltransferase displays absolute specificity for the R-3-OH moiety of R-3 hydroxymyristoyl-ACP, as does the O-acyltransferase, consistent with the placement of R-3-hydroxymyristate in E. coli lipid A. PMID- 8366126 TI - Signal transduction through a biomolecular receptor tyrosine protein kinase composed of a platelet-derived growth factor receptor-CD4 chimera and the nonreceptor tyrosine protein kinase Lck. AB - We have generated a novel "receptor tyrosine kinase" by fusing the extracellular and transmembrane domain of the mouse platelet-derived growth factor receptor (PDGFR) to the cytoplasmic domain of CD4 and coexpressing the construct with the murine cytoplasmic tyrosine protein kinase p56lck. NMuMG cells, which are mouse mammary gland epithelial cells that lack endogenous platelet-derived growth factor (PDGF) receptor expression, were stably transfected with both PDGFR-CD4 and p56lck. The PDGFR-CD4 chimeric protein was expressed at the cell surface and formed a complex with p56lck. Addition of PDGF to these cells led to increased tyrosine phosphorylation of a 56-kDa protein likely to be p56lck and several unidentified cellular proteins. The enzymatic activity of p56lck was increased after treatment with PDGF, indicating that dimerization (or oligomerization) mediated by ligand binding at the cell surface is capable of inducing the activation not only of receptor tyrosine kinases but nonreceptor tyrosine kinases as well. However, the PDGFR-CD4.p56lck complex was, in contrast to the wild type PDGF receptor, not able to induce a PDGF-dependent mitogenic response or DNA synthesis in NMuMG cells. Analysis of several known substrates of the PDGFR signaling pathway indicates an early block in the transduction of the signal generated by p56lck. PMID- 8366127 TI - Complementation of transport-deficient mutants of Escherichia coli alpha hemolysin by second-site mutations in the transporter hemolysin B. AB - Hemolysin B (HlyB) is a membrane-bound transport protein composed of an amino terminal multiple membrane-spanning portion followed by a conserved ATP binding sequence. Together with the inner membrane protein HlyD and the outer membrane protein TolC, HlyB is responsible for transport of the 107-kDa toxin HlyA from the cytoplasm, across both membranes of the cell envelope of Escherichia coli, directly to the medium. We have used a mutational approach to investigate a postulated interaction between HlyA and HlyB. We have isolated transport deficient mutants of HlyA altered in the C-terminal signal sequence and used one of these, a deletion of 29 amino acids, to select compensatory mutants in the transporter protein HlyB. Fifteen mutants located at six different sites, all mapping within the amino-terminal multiple membrane-spanning domain of HlyB, were identified. All of the mutations are clustered into three groups located close to the predicted inner face of the cytoplasmic membrane. We propose that these locations are close to sites on HlyB that interact with the C-terminal signal sequence of HlyA. This interaction is likely to involve either binding of HlyA to HlyB or activation of the transport mechanism. The compensatory mutants also display different patterns of specificity in terms of their ability to transport different HlyA mutants. The fact that point mutations are able to compensate for drastic changes in the signal sequence of HlyA suggests that substrate specificity of transporters such as HlyB may shift dramatically during evolutionary history. This could account for the diversity of substrates observed for the ABC transporter superfamily in nature. PMID- 8366129 TI - High resolution distribution of mRNA within the cytoskeleton. AB - It has been well documented that mRNA is associated with the cytoskeleton, and that this relationship is involved in translation and mRNA sorting. The molecular components involved in the attachment of mRNA to the cytoskeleton are only poorly understood. The objective of this research was to directly visualize the interaction of mRNA with the cytoskeleton, with sufficient resolution to identify the filament systems involved. This work required the development of novel in situ hybridization methods for use with electron microscopy. PMID- 8366128 TI - Import, processing, and two-dimensional NMR structure of a linker-deleted signal peptide of rat liver mitochondrial aldehyde dehydrogenase. AB - Previous NMR studies (Karslake, C., Piotto, M. E., Pak, Y. M., Weiner, H., and Gorenstein, D. G. (1990) Biochemistry 29, 9872-9878) had shown that a 22-amino acid signal peptide of rat liver aldehyde dehydrogenase (ALDH) when bound to a micelle had two amphiphilic alpha-helices, one located at the N terminus and the other at the C terminus. It was shown that deletion of either helix caused the precursor protein not to be imported (Wang, Y., and Weiner, H., (1993) J. Biol. Chem. 268, 4759-4765). The two helices are separated by a Arg-Gly-Pro flexible "linker" region, and to test the role of this linker region in the import and processing of the precursor protein, we deleted it from the ALDH signal peptide and precursor protein. The 19-amino acid signal peptide of ALDH, to which has been added 3 residues at the C terminus and from which has been deleted the 3 residue flexible linker region, has been studied by two-dimensional NMR in a dodecylphosphocholine micelle. In this membrane-like environment the peptide contains a single alpha-helical segment that extends almost the entire length of the peptide. NH exchange experiments show residues on the hydrophobic face of the peptide to exchange much more slowly than those of the hydrophilic face. Combined with the previous study, these results suggest that precursor protein import simply requires a sufficiently long amphiphilic helix (or helices) to bind stably to the membrane. The N and C helices of native ALDH are only about 6-8 residues long; this represents only about two turns of a helix, and either helix on its own does not provide enough stabilization to ensure folding and binding to the membrane. The linker-deleted ALDH peptide contains a single helix of 12-14 residues that is long enough to provide a hydrophobic surface that can stably interact with the hydrophobic interior of the membrane. The function of the C helix in the native signal peptide is therefore to enhance the stability and binding of the N-terminal signal to the membrane. Significantly, unlike native ALDH precursor protein, the linker-deleted signal peptide precursor protein could no longer be processed after import into mitochondria. As explained by modeling of the alpha-helix and the NH exchange rate data, the precursor protein requires that the first several residues of the mature protein be part of the hydrophobic membrane associated face of the helix.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8366130 TI - ABP50: an actin-binding elongation factor 1 alpha from Dictyostelium discoideum. AB - ABP50 is a polypeptide elongation factor 1 alpha from Dictyostelium that is associated with the actin cytoskeleton. Upon chemotactic stimulation, ABP50 undergoes a dramatic cytoplasmic redistribution into newly formed surface projections and in vitro binds to and bundles actin filaments. Many questions are raised by this interaction pertaining to the spatiotemporal regulation of protein synthesis and cytoskeletal organization by extracellular signals. PMID- 8366131 TI - Effect of cytoarchitecture on the transport and localization of protein synthetic machinery. AB - The emerging picture of cytoarchitecture imposes constraints on the transport and localization of several components of the protein synthetic machinery. The range in which "free" polysomes can diffuse through the cytoplasm may be restricted to about 50 nm due to obstruction by cytoskeletal barriers. Individual ribosomes and large transcripts will diffuse at least 4-10 times slower in cytoplasm than in dilute aqueous solution and may be sterically excluded from some cytoplasmic domains. The transport of these components from the nucleus to the cell periphery may be restricted to microtubule-containing channels that traverse the excluding domains. In the peripheral cytoplasm, mitochondria, endoplasmic reticulum, and other membrane-bound organelles are found only in nonexcluding channels, while actin, nonmuscle filamin (ABP280), and fodrin are concentrated in excluding domains. This suggests that the cytoplasmic volume may be functionally compartmentalized by local differentiations of cytoarchitecture. Excluding compartments may play a structural role, while nonexcluding compartments are the site of vesicle traffic and protein synthesis. PMID- 8366132 TI - Spatial organization of the synthesis of cytoskeletal proteins. AB - The cytoskeleton of most cells is complex and spatially diverse. The mRNAs for some cytoskeletal proteins are localized, suggesting that synthesis of these proteins may occur at sites appropriate for function or assembly. mRNA concentrations were first observed for several oocyte and embryonic mRNAs. Some insight has been gained into the mechanisms that help to position these mRNAs. More surprising to some, many cytoskeletal mRNAs are also localized. Among them are mRNAs for actin, tubulin, intermediate filaments, and a variety of associated proteins. Different mRNAs in the same cell can be located in different places; the same mRNA can be located in different places; the same mRNA can be located differently at different times of development. For example, we observed vimentin mRNA in developing chicken muscle cultures by fluorescent in situ hybridization. We found that vimentin mRNA takes on a variety of positions during myogenesis, ending up located with its cognate protein at costameres. This last pattern is significant because it is too finely structured to have a function in the soluble phase and probably reflects cotranslational assembly of this particular protein. Analogies can be made between oocyte or embryonic positions (animal/vegetal poles, oocyte cortex, and interior) and somatic cell positions (anterior/posterior and cell cortex/cell center). These analogies may point to conserved mechanisms for moving and retaining mRNA. Localization of cytoskeletal synthesis, through the mRNA or by other means, may prove as important for assembling and maintaining differentiated cytoskeletal structures and somatic cells as mRNA location is for organizing the embryo. Mechanisms that permit mRNA localization are likely to be conserved. PMID- 8366133 TI - ADP-ribosylation of nucleolar proteins in HeLa tumor cells. AB - ADP-ribosylation reactions in nucleoli of exponentially growing HeLa cells were studied. Isolated nuclei or nucleoli were labeled with 32P-NAD; then the nucleolar proteins were analyzed by 1-dimensional and 2-dimensional polyacrylamide gel electrophoresis (PAGE) and modified proteins were detected by autoradiography. The labeled nucleolar proteins were also chromatographically fractionated on DEAE-cellulose. Electrophoretic analysis of total nucleolar and chromatographically purified proteins revealed that besides nuclear ADP ribosyltransferase and histones two characteristic nucleolar phosphoproteins numatrin/B23 and nucleolin/C23 were modified by ADP-ribosylation. PMID- 8366134 TI - 1,25-Dihydroxyvitamin D3 increases type 1 interleukin-1 receptor expression in a murine T cell line. AB - The biologically active metabolite of vitamin D3, 1,25 (OH)2 D3, exerts important immunoregulatory effects in addition to being a central mediator of calcium/phosphate metabolism. Utilizing an interleukin 1 responsive murine T cell line and 125I-interleukin 1 alpha, we show that 1,25 (OH)2 D3 (5,50 nM) enhanced 125I-interleukin 1 alpha binding up to almost 2-fold over control. This 1,25 (OH)2 D3 effect occurred in a dose-dependent manner and was detectable after 24 h but not before 7 h of culture. Scatchard analysis of 125I-interleukin 1 alpha binding data demonstrated that 1,25 (OH)2 D3 enhanced interleukin 1 receptor number without a significant change in affinity. The biologically less potent metabolite of vitamin D3, 25 (OH) D3, also augmented 125I-interleukin 1 alpha binding but at steroid levels 2-3 log orders greater than 1,25 (OH)2 D3. This observation, combined with the presence of high-affinity 3H-1,25 (OH)2 D3 receptors (88 sites/cell, K = 0.45 nM) in cytosolic extracts, strongly suggests that the nuclear vitamin D receptor mediates this steroid's effect on interleukin 1 receptor expression. Based on the capacity of an anti-type 1 interleukin 1 receptor monoclonal antibody (35F5) to block 1,25 (OH)2 D3-enhanced 125I interleukin 1 alpha binding, we conclude that this steroid augments type 1 interleukin 1 receptor expression. When combined with interleukin 1, a cytokine that also impacts MD10 interleukin 1 receptor expression, 1,25 (OH)2 D3 enhanced interleukin 1 receptor expression. Northern blots hybridized with a 32P-type 1 interleukin 1 receptor cDNA probe show that 1,25 (OH)2 D3 enhanced type 1 interleukin 1 receptor steady state mRNA levels. Functionally, 1,25 (OH)2 D3 pretreatment augmented the MD10 proliferative response to suboptimal levels of interleukin 1 (< 100 fM interleukin 1 alpha). These findings further support 1,25 (OH)2 D3's role as an immunoregulatory molecule and provides a possible mechanism by which this steroid could potentiate certain immune activities. PMID- 8366135 TI - Inhibition of induced endochondral bone development in caffeine-treated rats. AB - We have addressed questions raised by the observation in fetal rats of delayed ossification induced by caffeine at maternal doses above 80 mg/kg body weight per day. The effect of caffeine on endochondral bone development and mineralization has been studied in an experimental model system of bone formation which involves implantation of demineralized bone particles (DBP) in subcutaneous pockets of young growing rats. Caffeine's effects on cellular events associated with endochondral ossification were examined directly by quantitating cellular mRNA levels of chondrocyte and osteoblast growth and differentiation markers in DBP implants from caffeine-treated rats harvested at specific stages of development (day 7 through day 15). Oral caffeine administration to rats implanted with DBP resulted in a dose dependent inhibition of the formation of cartilage tissue in the implants. Histologic examination of the implants revealed a decrease in the number of cells which were transformed to chondrocytes compared to control implants. Those cartilaginous areas that did form, however, proceeded through the normal sequelae of calcified cartilage and bone formation. At the 100 mg/kg dose, cellular levels of mRNA for histone, collagen type II, and TGF beta were all reduced by greater than 40% of control implants consistent with the histological findings. Alkaline phosphatase activity in the implants and mRNA levels for proteins reflecting the hypertrophic chondrocyte and bone phenotype, collagen type I and osteocalcin were markedly decreased compared to controls. Lower doses of 50 and 12.5 mg/kg caffeine also resulted in decreased cellular proliferation and transformation to cartilage histologically and reflected by significant inhibition of type II collagen mRNA levels (day 7). The effects of caffeine on gene expression observed in vivo during the period of bone formation (day 11 to day 15) in the DBP model were similar to the inhibited expression of H4, alkaline phosphatase, osteocalcin, and osteopontin found in fetal rat calvarial derived osteoblast cultures following 24 hour exposure of the cultures to 0.4 mM caffeine. Thus the observed delayed mineralization in the fetal skeleton associated with caffeine appears to be related to an inhibition of endochondral bone formation at the early stages of proliferation of undifferentiated mesenchymal cells to cartilage specific cells as well as at later stages of bone formation. PMID- 8366136 TI - Biosynthesis and function of membrane bound and secreted forms of recombinant CD11b/CD18 (Mac-1). AB - Full-length (membrane bound) and truncated (secreted) forms of the beta 2 integrin heterodimer, CD11b/CD18 (Mac-1), were expressed in a human kidney cell line (293) that normally does not express leukocyte adhesion molecules (Leu CAMs). The biosynthesis of recombinant Mac-1 in 293 cells differed from that reported for leukocytes in that heterodimer formation was not required for CD11b to be exported to the cell surface. A stable cell line was constructed that constitutively secreted the recombinant, truncated Mac-1 heterodimer into growth conditioned cell culture medium. A novel monoclonal antibody that enabled an immunoaffinity method for the selective purification of recombinant Mac-1 heterodimers was identified. Sufficient protein was purified to allow the first measurement of the 50% inhibitory concentration (IC50) for CD11b/CD18 and for the direct comparison of the inhibitory activity of recombinant soluble Mac-1 with that of various CD18 and CD11b specific monoclonal antibodies. Purified recombinant soluble Mac-1 inhibited the binding of neutrophils, activated by opsonized zymosan or fMet-Leu-Phe peptide, to human umbilical vein endothelial cells. Similarly, the recombinant integrin was effective in inhibiting the binding of unactivated neutrophils to tumor necrosis factor (TNF-alpha) activated endothelial cells. The availability of an abundant source of purified, biologically active Mac-1 will enable direct physical and chemical investigations into the relationship between the structure and function of this leukocyte adhesion molecule. PMID- 8366137 TI - Induction of bone-related proteins, osteocalcin and osteopontin, and their matrix ultrastructural localization with development of chondrocyte hypertrophy in vitro. AB - Endochondral bone formation occurs by a series of developmentally regulated cellular events from initial formation of cartilage tissue to stages of calcified cartilage, resorption, and replacement by bone tissue. Several studies have raised the question of the possibility that the hypertrophic chondrocytes associated with the calcifying cartilage matrix can acquire properties similar to osteoblasts. We have addressed this possibility by measuring synthesis within hypertrophic chondrocytes in vitro of two bone-related proteins, osteopontin and osteocalcin. Chondrocytes derived from chick embryo ventral vertebral tissue were cultured under conditions that promoted extracellular matrix mineralization and differentiation towards the hypertrophic phenotype as indicated by the induction of Type X collagen, alkaline phosphatase, and diminished expression of Type II collagen and the core protein of large proteoglycan. In these cultures, osteopontin synthesis was detected in early cultures in the absence of a calcified matrix; in contrast, an absence of the bone-specific protein osteocalcin was observed. However, with onset of development of the hypertrophic phenotype an induction of protein expression for osteocalcin was observed with a significant (twofold) increase in osteopontin. Maximal levels of osteocalcin synthesis occurred with the peak of alkaline phosphatase activity and Type X collagen mRNA levels. The levels of osteocalcin synthesis were induced fiftyfold from the earliest level of detection but this level was only one one-hundredth of that observed for mature chick osteoblast cultures. Osteocalcin and osteopontin were characterized by several criteria (electrophoresis, immunoblotting, chromatographic characteristics, and response to 1,25(OH)2D3) which confirmed their molecular properties as being identical to osteoblast synthesized proteins. The coordinate change in the cellular phenotype to the hypertrophic chondrocyte was shown to be concurrent with ultrastructural maturation of the cells and the accumulation of osteocalcin and osteopontin in the extracellular matrix associated with hydroxyapatite at sites of mineralization. Since the ultrastructural features of the cells in vitro and the extracellular matrix surrounding the lacunae have features of the hypertrophic chondrocyte and associated matrix in vivo, the induction of the bone-specific protein osteocalcin suggests that at least a population of these cells may develop osteoblastic phenotypic markers in association with mineralizing matrix. The detection of osteocalcin and the high level of synthesis of osteopontin may represent an advanced stage of chondrocyte hypertrophy or the possibility of a trans differentiation of the chondrocytes to an osteoblastic-like cell. PMID- 8366138 TI - Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells. AB - Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells. PMID- 8366139 TI - Evidence for calcium mediated conformational changes in calbindin-D28K (the vitamin D-induced calcium binding protein) interactions with chick intestinal brush border membrane alkaline phosphatase as studied via photoaffinity labeling techniques. AB - The role of the vitamin D-induced calcium binding protein termed calbindin-D (CaBP) in the biological response to 1,25-dihydroxyvitamin D3 was assessed by photoaffinity labeling techniques. The heterobifunctional cross-linking reagent methyl-4-azidobenzoimidate was employed for studies with the 28 KD chick intestinal calbindin-D28K. Calcium-dependent interactions were evident with purified chick intestinal CaBP-immunoglobulins and bovine intestinal alkaline phosphatase; in the absence of Ca2+ there was a greatly diminished crosslinking process. There were also at least two membrane components of chick intestinal brush border membranes, with M(R) = 60,000 and 130,000, which were photoaffinity cross-linked with CaBP in a calcium-dependent manner. Similar interactions were demonstrated following incubations of CaBP with phosphatidylinositol-specific phospholipase C (PI-PLC)-treated supernatant fractions from chick intestinal brush borders. PI-PLC was shown to release 14% of the alkaline phosphatase from chick intestinal brush borders compared to greater than 80% for rabbit and chick kidney BBM preparations. Specific interactions between CaBP and brush border membrane proteins could also be demonstrated in the absence of photoaffinity labeling by Sephadex G-150 chromatography of Triton X-100 solubilized incubations between calbindin-D28K and chick intestinal BBMS, with 17% of the radiolabelled CaBP comigrating with alkaline phosphatase activity. These studies collectively demonstrate that calbindin-D28K undergoes calcium-dependent conformational changes which alter its subsequent interactions with cellular proteins in a way consistent with other calcium-binding proteins such as calmodulin or troponin C. PMID- 8366141 TI - Centrosome reorientation in regenerating endothelial monolayers requires bFGF. AB - Monolayers of endothelial cells respond to physical denudation with a characteristic sequence of lamellipodia extrusion, cell migration, and cell proliferation. Basic fibroblast growth factor (bFGF) has been implicated as a necessary component of this process: addition of exogenous bFGF enhances monolayer regeneration both in vitro and in vivo, and monolayer regeneration can be inhibited in vitro by treatment with neutralizing antibodies raised against bFGF. Centrosome reorientation from a random location to one preferentially situated between the nucleus and the denudation edge has been postulated as a mechanism essential for cell polarization and subsequent migration. This present study examined the effects of a polyclonal antibody to bFGF and suramin on monolayer regeneration, actin microfilament staining, and centrosome orientation at the wound edge of partially denuded bovine large vessel endothelial monolayers. Treatment with anti-bFGF or suramin abolished monolayer repair in these cultures. Cells at the denudation edge showed altered actin staining patterns and reduced lamellipodia extrusion, and there was complete inhibition of centrosome reorientation in treated cultures. Monolayer repair and centrosome reorientation could be restored by addition of exogenous bFGF in antibody but not suramin treated cultures. Recent evidence suggests that preferential centrosome location in migrating cells may be a consequence of lamellipodia protrusion and cell spreading, rather than an indication of cell polarization. However, these results indicate that agents which interfere with bFGF availability prevent endothelial monolayer regeneration via mechanisms involving cell spreading and/or centrosome reorientation. PMID- 8366142 TI - Heat-induced morphological and biochemical changes in the nuclear lamina from Ehrlich ascites tumor cells in vivo. AB - Membrane-depleted nuclei from Ehrlich ascites tumor (EAT) cells isolated at low ionic strength in the presence of EDTA exhibit highly decondensed chromatin fibers and a loss of morphologically identifiable nucleoli. Treatment of these nuclei with nucleases and 2 M NaCl followed by low-speed centrifugation permitted the facile isolation of the nuclear lamina layer. Under the same conditions, but after heat-shock treatment of the living cells, the chromatin appears in a more condensed state, the nucleoli are well-defined, and the nuclear lamina layer was destabilized in concert with the appearance of an internal nuclear matrix and nucleolar skeleton. Furthermore, we also found both an increase in the protein mass as well as the appearance of a relatively large number of new proteins in this fraction, which are phosphorylated. The major proteins of the nuclear lamina, the lamins, and the residual vimentin remained insoluble. These heat shock-induced changes were also accompanied by a dephosphorylation of lamins A and C but not of lamin B. PMID- 8366140 TI - Induction of vimentin modification and vimentin-HSP72 association by withangulatin A in 9L rat brain tumor cells. AB - Withangulatin A induced cell rounding up and the morphological alteration resulted from the reorganization of all of the major cytoskeletal components, i.e., vimentin, tubulin, and actin, as revealed by immunofluorescence techniques. When the withangulatin A-treated cells changed to a round-up morphology, vimentin intermediate filaments were found to be collapsed and clustered around the nucleus. The alteration was accompanied by characteristic changes of vimentin molecules, including augmentation of phosphorylation, retardation of electrophoretic mobility, and decrease in detergent extractability. The levels of vimentin phosphorylation were augmented by 2.5- and 1.8-fold in cells incubated with 50 microM withangulatin A for 1 and 3 h, respectively. The electrophoretic mobility of vimentin was partially retarded in cells treated with withangulatin A for 1 h at 10 microM and a completely upshift mobility was observed after 5 h treatment at 50 microM. In addition, vimentin molecules became less extractable by nonident P-40 after the cells were treated with withangulatin A and this effect was dose dependent. The decrease in solubility of vimentin was accompanied by the redistribution of HSP72 into the detergent nonextractable fraction and these two events were well correlated. Our results suggest that withangulatin A induced the modification of vimentin, which resulted in the alteration of cell morphology and redistribution of intracellular HSP72, an event that may play an important role in the induction of heat-shock response. PMID- 8366143 TI - Phorbol ester activation of functional rat protein kinase C beta-1 causes phenotype in yeast. AB - The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of various eukaryotic cellular signals. The molecular dissection of its mechanisms of action has been limited in part by the genetic inaccessibility and complexity of signaling in mammalian cells. Here we present a novel approach to study rat PKC beta-1 action in yeast, a simple lower eukaryotic genetic model. Expression of its cDNA in Saccharomyces cerevisiae introduces novel phorbol ester binding sites which stimulate a specific calcium- and phospholipid-dependent catalytic activity in vitro consistent with a fully functional protein which phosphorylates cellular yeast proteins in vivo. Phorbol ester activation of PKC beta-1 in vivo results in biological responses which include stimulation of extracellular calcium uptake, changes in cell morphology, and an increase in the cell doubling time. These PKC functions are not affected by truncation of 12 amino terminal amino acids; however, they are completely abolished by truncation of 15 or more carboxyl terminal amino acids which likely result in inactivation of the kinase. The increase in the yeast doubling time caused by PKC beta-1 activation provides a phenotype which can be exploited as a screen for the activity of random PKC cDNA mutations. Our findings indicate that rat PKC beta-1 is functional in yeast and leads to biological responses which suggest compatible aspects of higher and lower eukaryotic signaling pathways and the feasibility of dissecting parts of the action of common signaling mediators in a simple genetic model. PMID- 8366144 TI - Effect of gallium nitrate in vitro and in normal rats. AB - Gallium nitrate (GN) is an inhibitor of bone resorption and thereby may result in a change in coupled bone formation. In the present investigation the effects of GN on bone formation were studied in the rat osteosarcoma (ROS) 17/2.8 cell line and normal diploid rat osteoblasts (ROB) in vitro and the femur of rats treated in vivo, measuring mRNA levels for two osteoblast parameters, type I collagen, a marker of matrix formation, and osteocalcin, a bone specific protein and also histone H4, a marker of cell proliferation. GN, at 50 microM for 3 h, increased type I collagen mRNA levels by 132% in ROS 17/2.8 cells and by 122% in proliferating ROB cells. Osteocalcin (OC) mRNA levels were decreased by 61% in ROS 17/2.8 cells and by 97% in differentiated ROB cells. These changes occurred in the absence of any effects on cell proliferation. Seventy-day-old female rats were then treated with GN, 0.5 mg/kg/day, for 3 weeks. As previously reported, GN decreased serum calcium levels, but had no effect on lumbar or femoral bone density. In contrast to the in vitro effects, GN had no effect on type I collagen steady-state mRNA levels in the femur; however, it decreased OC steady-state mRNA levels in the femur by 58%. These results suggest that GN has similar in vitro effects in transformed and normal osteoblasts, while the collagen-stimulatory effects observed in vitro cannot be extrapolated to in vivo models. The consistent inhibition of osteocalcin in vitro and in vivo suggests a more specific target for GN that may relate to its effects in inhibiting bone resorption in normal rats. PMID- 8366146 TI - Resistance of mitochondrial DNA to degradation characterizes the apoptotic but not the necrotic mode of human leukemia cell death. AB - Cell death can occur by two basically different processes. The original term, necrosis, is now reserved for the generally destructive series of events which include the release of lysosomal enzymes and loss of cell membrane integrity. In contrast, mild treatment with cell damaging agents, or withdrawal of growth factors, may result in a characteristic form of degradation of cellular DNA which is associated with cell death that has morphology known as apoptosis. In this study human leukemia cells were exposed to agents or conditions previously reported to cause necrosis or apoptosis, monitored by detection of DNA "ladders," and the integrity of cellular DNA was determined on Southern blots. Nuclear DNA was distinguished from mitochondrial DNA by use of probes specific for nuclear genes or for mitochondrial DNA. When HL60, K562, MOLT4, or U937 cells were exposed to conditions which resulted in necrosis, mitochondrial DNA was damaged at approximately the same rate as nuclear DNA, but in apoptosis mtDNA was not degraded. Thus, the ratio of the relative (to untreated cells) abundance of mitochondrial DNA measured by a probe for 16S mitochondrial ribosomal RNA on Southern blots, to the relative abundance of DNA of any nuclear gene, was 1 or less in necrosis, but rose to values greater than 2 in apoptosis. It is concluded that the comparison of the degree of fragmentation of mitochondrial and nuclear DNA provides a quantitative way of distinguishing necrosis from apoptosis. PMID- 8366145 TI - Novel phorbol ester response region in the collagenase promoter binds Fos and Jun. AB - In rabbit fibroblasts the AP-1 sequence (5'-ATGAGTCAC-3') is necessary but not sufficient for induction of collagenase transcription by phorbol esters (PMA) (Auble and Brinckerhoff: Biochemistry 30(18):4629-4635, 1991). In this study we identified additional sequences involved in PMA-induced transcription. Using fibroblasts transiently transfected with chimeric constructs containing fragments of the rabbit collagenase 5'-flanking DNA linked to the chloramphenicol acetyl transferase (CAT) gene, we found that deletion of nucleotides -182 to -141 in a 380 bp promoter construct resulted in about a 7-fold loss of induction by PMA. Mobility shift assays revealed that nuclear proteins from fibroblasts specifically bound to 20-bp at -182 to -161. Binding was competed completely by self and only partially by the AP-1 sequence, implying that proteins binding to the AP-1 sequence could also bind to this region. In vitro transcribed and translated c-Fos and c-Jun bound to both the AP-1 site and to the sequences from 182 to -141. DNAase I footprinting of the collagenase promoter with purified c Jun or c-Fos/c-Jun protected the AP-1 sequence at -77 to -69 in addition to a region from -189 to -178 which overlaps a putative AP-1-like site, 5'-ATTAATCAT 3'. Finally, deletion of the -182 to -161 region in a 380-bp CAT construct resulted in a substantial reduction of PMA responsiveness. Thus, we have identified a novel phorbol-responsive region that binds c-Fos and c-Jun, and we suggest that these or similar proteins may regulate transcription of the collagenase gene by binding to sequences within and adjacent to the -182 to -161 region. PMID- 8366147 TI - Chem-X and CAMBRIDGE. Comparison of computer generated chemical structures with X ray crystallographic data. AB - The structures of a number of molecules as determined by X-ray crystallography have been compared with the structures for the same molecules as calculated by the 3D structure generation program, Chem-X. In the group of molecules examined, ChemModel produced structures that were essentially identical to those based upon X-ray data in 57% of the cases. The corresponding figure for the widely used alternative model builder, CONCORD, was 38%. The superior performance of ChemModel was due entirely to that program's ability to generate multiple structures covering the entire conformational space. PMID- 8366148 TI - Hospital-acquired tuberculosis: addressing the challenge. AB - Treating contagious patients as outpatients is, of course, the best way to prevent nosocomial transmission. When hospitalized, they should be confined to areas with specified ventilation systems. Guidelines for monitoring exposed persons are presented. Immune status and drug-resistant organisms are prime considerations in managing both the exposed and those with active TB. PMID- 8366149 TI - Back to the Old Soldiers' Home? PMID- 8366150 TI - Heart failure: its progression and its therapy. AB - The complex pathology that leads to heart failure has hampered the search for optimal therapy. Even so, ACE inhibitors have become a cornerstone of treatment. After an acute MI, the goal of ACE inhibition is to limit LV remodeling and progression to ischemic cardiomyopathy and congestive failure. In advanced failure, the goal is to reverse peripheral vascular changes and ameliorate symptoms. PMID- 8366151 TI - A man who drank a breathtaking bottle of wine. PMID- 8366152 TI - Recurrent pulmonary infection in an infant. PMID- 8366153 TI - Fainting spells. PMID- 8366154 TI - Financial recognition. PMID- 8366155 TI - CEO,OOO,OOO. Oh! Oh! PMID- 8366156 TI - Wide QRS complexes in acute myocardial infarction. PMID- 8366157 TI - Aggressive drug therapy for rheumatoid arthritis. AB - Recent data indicate that rheumatoid arthritis is more often systemic, progressive, and disabling than benign, and that it reduces life expectancy. The new evidence argues for a dramatic alteration in pharmacologic management. If several months of rest, exercise, and anti-inflammatory therapy are ineffectual, aggressive treatment with disease-modifying antirheumatic and immunosuppressive agents may be in order. PMID- 8366158 TI - Isolated systolic hypertension in the elderly. PMID- 8366159 TI - Bites from pet animals. PMID- 8366160 TI - Enantiomeric separation of fluorescent, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, tagged amino acids. AB - A new derivatizing reagent, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC), has been used successfully for chromatographic enantioseparation of 31 amino acids on cyclodextrin bonded stationary phases. AQC reacts with both primary and secondary amino acids to produce stable and highly fluorescent derivatives suitable for efficient and sensitive chromatographic determinations. The derivatization reaction proceeds without detectable racemization. The detection limit is in the femtomole range and approximately 0.0075% of the D enantiomer in an excess of the L-enantiomer is detectable. High resolution values are needed when determining trace enantiomeric impurities. PMID- 8366161 TI - Comparison of flame ionization and inductively coupled plasma mass spectrometry for the detection of organometallics separated by capillary supercritical fluid chromatography. AB - Organotin compounds are separated by capillary supercritical fluid chromatography (SFC) and a comparison of the detection by flame ionization (FID) and inductively coupled plasma mass spectrometry (ICP-MS) is presented. Resolution, detection limits, linear dynamic range and reproducibility are the parameters compared between SFC-FID and SFC-ICP-MS, for the detection of tri- and tetraorganotin compounds. The resolution obtained in the SFC-FID system is not always observed in SFC-ICP-MS. Degradation in resolution is due to fluctuations in transfer line temperature. Baseline resolution for the organotins considered is achieved in both systems by using a longer column. Detection limits (DLs) are calculated as 3 sigma/S, where sigma is the standard deviation of the blank signal and S is the slope of the calibration curve. Detection limits of 10.3, 12.5, 12.0 and 9.0 pg are obtained for tetrabutyltin, tributyltin chloride, triphenyltin chloride and tetraphenyltin, respectively, using SFC-FID. An improvement in detection limits of one order of magnitude is achieved by SFC-ICP-MS for the same organotins (0.26, 0.80, 0.57 and 0.20 pg, respectively). The relative standard deviations using SFC-FID for five 50-nl injections, containing 0.5 ng Sn, ranged from 3.2 to 6.4%. Using SFC-ICP-MS, five replicate injections of 0.05 ng Sn give R.S.D.s from 1.3 to 3.4%. PMID- 8366162 TI - 4-(Trifluoromethyl)-2,3,5,6-tetrafluorobenzyl bromide as a new electrophoric derivatizing reagent. AB - 4-(Trifluoromethyl)-2,3,5,6-tetrafluorobenzyl bromide (TTBB) was synthesized in a single step from alpha,alpha,alpha,2,3,5,6-heptafluoro-p-xylene. The purpose of TTBB is to function as an analogue of pentafluorobenzyl bromide (PFBB) in electrophoric derivatization reactions prior to detection by gas chromatography electron-capture negative ion mass spectrometry (GC-ECNI-MS). In more detail, it was anticipated that TTBB could be used along with, or as a substitute for, PFBB to help control some interferences and confirm results. This is because a TTBB product (of an analyte) would have different retention and sometimes m/z characteristics than a corresponding PFBB product in GC-ECNI-MS, while the two products should be similar in their ease of formation and yields. Results demonstrating these expectations were achieved by derivatizing and detecting two analytes with these reagents: N7-(2-hydroxyethyl)xanthine, and 2,3 pyrenedicarboxylic acid. PMID- 8366163 TI - Solid-phase extraction in multi-residue pesticide analysis of water. AB - The determination of pesticides in water is fundamental to the solution of environmental problems as natural waters are usually contaminated with a large number of pesticides. The selection of an isolation and/or concentration technique depends largely on the class of pesticides to be determined. It is often necessary to determine simultaneously a wide variety of compounds in a water sample. Application of solid-phase extraction techniques offers a solution. The mechanisms of solid-phase extraction, types of sorbents and their application to multi-residue pesticide analysis are reviewed. PMID- 8366164 TI - Re-evaluation of solid-phase adsorption and desorption techniques for isolation of trace organic pollutants from chlorinated water. AB - Amberlite XAD resin and activated carbon columns were tested for their abilities to concentrate trace organic pollutants in chlorinated water. Both XAD-2 and XAD 7 resin columns (20 ml) were capable of adsorbing about 30% of total organic halogen (TOX) present in 20 l of drinking water (pH 7) containing about 100 micrograms/l of TOX, whereas the carbon column (10 ml) adsorbed over 90% of TOX. The adsorption capacity of XAD-7 resin was found to be strongly dependent on the solution pH, as compared with those of XAD-2 and carbon adsorbents. Soxhlet and sonication extractions were also evaluated for their abilities to recover the adsorbed organics from the adsorbents, by measurements of TOX, chromatographable compounds and mutagenicity in the eluates. Soxhlet extraction gave higher recoveries than sonication, as measured with the above indices, but these differences were generally small (ca. 20%), with exception of the carbon extracts. The XAD-2 and XAD-7 extracts of drinking water also showed about 3-4 times higher mutagenic activity than the carbon extracts. PMID- 8366165 TI - Evaluation of a solid-phase extraction system for determining pesticide residues in milk. AB - A simple and rapid procedure based on reversed solid-phase extraction with octadecylsilica was developed for determining chlorinated pesticide residues in milk. The need for an agent that breaks the fat globules was first investigated and the method variables were optimized on whole homogenized milk (3.6% fat content). Recovery experiments performed for 26 organochlorine pesticides at levels of 3-40 micrograms/l gave > 80% recoveries for all the compounds. The method was validated and evaluated by comparison with two widely used liquid liquid extraction methods. The performance was checked by analysis of a certified standard with natural low endogenous levels (CMR 187) and different kinds of milk (skimmed, 2%, powdered, evaporated and condensed) spiked with the 26 pesticides. The procedure was used to analyse 45 commercial milks in which the presence of organochlorine residues had been detected. The proposed method offers advantages such as low cost and simplicity and the fact that the extracts obtained do not require a purification step. PMID- 8366166 TI - Chemiluminescent detection of potato and pome fruit viroids by digoxigenin labeled dot blot and tissue blot hybridization. AB - A chemiluminescent molecular hybridization protocol was compared to 32P autoradiography for detecting potato spindle tuber viroid (PSTVd) and apple scar skin group viroids (ASSVd). Labeled cRNA probes for PSTVd and ASSVd were synthesized by SP6 RNA polymerase transcription using digoxigenin-11-UTP or alpha [32P]UTP. Dot blot hybridization of purified viroids and sap extracts from infected plants showed that chemiluminescent detection using digoxigenin-labeled probes was as sensitive as autoradiography using 32P probes. A minimum of 2.0-2.5 pg purified viroid was detected. ASSVd could be detected in as little as 0.4 ng of total nucleic acid extract from infected tissue or in sap extracts diluted to 10(-3) with healthy extracts. Tissue blots of PSTVd-infected potato tubers and tomato roots, stems and leaves and ASSVd-infected apple fruit, stems and petioles, gave positive reactions when hybridized with the digoxigenin probe. No reaction with similar tissues from healthy plants was observed. PMID- 8366167 TI - Expression in baculovirus vector system of the nucleocapsid protein gene of rinderpest virus. AB - The rinderpest (RV) nucleocapsid (NP) gene segment was inserted into the genome of Autographa californica nuclear polyhedrosis virus (AcNPV) adjacent to the polyhedrin promoter. The expression of NP protein in Sf9 cells was confirmed by indirect immunofluorescence and by Western blotting analysis with monoclonal antibodies. Recombinant RV-NP protein was purified by ultracentrifugation on a sucrose density gradient, and used as an antigen for an enzyme linked immunosorbent assay to detect anti RV-NP antibody. Both IgM and IgG antibodies against RV-NP were detected in the sera of rabbits infected with the L strain of RV. The pattern of development of IgG anti RV-NP antibody closely correlated with that of virus neutralizing antibody. In rabbits inoculated with recombinant vaccinia virus expressing RV-H gene (RRV-H), anti RV-NP was not detected. The results indicated that the baculovirus vector system can be used for the preparation of the diagnostic antigen of rinderpest as well as to distinguish between natural infection and vaccination with RRV-H. PMID- 8366168 TI - Quantification of HIV-1 RNA in plasma using NASBA during HIV-1 primary infection. AB - Quantification of HIV-1 viral RNA in plasma was achieved by competitive co amplification of a dilution series of in vitro generated RNA using the nucleic acid sequence based amplification (NASBA) technology. This 1.5 kilobase in vitro RNA, comprising the gag and part of the pol region, differs only by sequence randomization of a 20 nt fragment from the wild-type RNA, ensuring equal efficiency of amplification. In model systems the accuracy of this method is within one log. Application of the Q-NASBA to plasma samples of a patient with a primary HIV-1 infection shows good concordance of the HIV-1 RNA profile with the p24 antigen profile. However, the HIV-1 RNA determination is more sensitive than the p24 antigen determination. Peak values of HIV-1 RNA are around 10(8) RNA molecules per ml plasma at the moment of seroconversion. Quantitative nucleic acid detection methods, like Q-NASBA, allow the monitoring of HIV-1 RNA during the course of infection which might have predictive value for disease development. PMID- 8366169 TI - Epizootic haematopoietic necrosis virus (EHNV): improved ELISA for detection in fish tissues and cell cultures and an efficient method for release of antigen from tissues. AB - An improved antigen capture ELISA for the detection of epizootic haematopoietic necrosis virus (EHNV) is described. Affinity purified rabbit anti-EHNV immunoglobulin was used as capture antibody, enabling the detection of EHNV at a concentration of 10(3.5) TCID50/ml cell culture supernatant. The sensitivity and specificity of the ELISA, determined by examination of clarified tissue homogenates from 55 infected fish and 348 uninfected fish in relation to virus isolation, were 81.2% and 98.9%, respectively. Specificity for redfin perch (Perca fluviatilis) tissue samples was 100%, however, high background optical density (OD) in samples from uninfected rainbow trout (Oncorhynchus [corrected] mykiss) resulted in lower specificity (98.5%). Specificity for rainbow trout tissues was increased to 100% by testing clarified tissue homogenates that had been diluted 1:10. Sensitivity and specificity estimates for cell culture supernatants were 96.2% and 99.9% based on the results obtained for 158 infected and 355 uninfected samples. Incubation steps in the ELISA can be shortened to enable its completion in less than 4 h if a rapid qualitative diagnosis is required. Of eight methods of releasing EHNV from infected tissue that were evaluated, manual grinding of tissue with a fitted pestle in a 1.5-ml plastic disposable tube, followed by vortexing in the same tube with 3 mm diameter glass beads and clarification in a microcentrifuge was the most efficient. Samples from 150-200 individual fish could be prepared for ELISA and cell culture by a single operator in a day. Antigen capture ELISA can replace virus isolation as the method of choice for diagnosis of EHNV. PMID- 8366170 TI - Quantitative and sensitive detection of immune-complexed and free HIV antigen after boiling of serum. AB - 5-min boiling of 3-fold diluted serum leads to the quantitative release of immune complexed HIV antigen (Ag) that can be readily measured. The method is capable of detecting as little as 4 to 5 pg/ml Ag p24 depending on the Ag test used. Of a panel of 50 anti-HIV-positive sera, 30 (60%) were Ag-positive after heat denaturation, 17 (34%; P < or = 0.01) after acidification, and 13 (26%; P < or = 0.001) when tested undenatured. The superiority of heat denaturation was greatest in sera with high-titered antibodies to p24. Occurrence and mean concentrations of heat-denatured Ag were reversely correlated with p24-specific antibody. It is suggested that heat-denatured proteins be used for raising antibodies that will serve as capture or trace antibodies in Ag assays. This simple change in the manufacturing of test reagents in combination with a short boil before testing may solve the problem of incomplete Ag detection due to immune complex formation. PMID- 8366171 TI - Evaluation of 3 nonradioactive DNA detection systems for identification of herpes simplex DNA amplified from cerebrospinal fluid. AB - The efficiencies of 4 different hybridization assays, using probes labeled with 32P, digoxigenin (DIG) and biotin, were compared for the detection of herpes simplex virus (HSV) DNA amplified from cerebrospinal fluid during herpes simplex encephalitis (HSE). The biotinylated probe was shown to provide a clearly lower sensitivity than the radioactive hybridization system, regardless of whether the biotin-labeled probe was detected by a colorimetric or by a photobiotin assay. In contrast, the DIG system, which includes a luminescent detection step was shown to be equivalent to the 32P system, at least at lower template concentrations. Although generally higher background signals were observed with the DIG assay the analysis of 73 CSF samples yielded identical results with the 32P and the DIG test systems in all cases, identifying concordantly an HSE in 6 patients. Since the time necessary for the performance of both assays is similar the DIG system seems to be a powerful alternative to the radioactive detection of amplified HSV DNA. PMID- 8366173 TI - 9th Annual meeting of the European Society of Human Reproduction and Embryology. Thessaloniki, Greece, 27-30 June 1993. Abstracts. PMID- 8366172 TI - A polymerase chain reaction method adapted for selective amplification and cloning of 3' sequences of potyviral genomes: application to dasheen mosaic virus. PMID- 8366174 TI - What is nitric oxide and why are so many people studying it? AB - From social outcast to citizen of the year in less than a decade is the stuff of fiction. That is precisely what has happened, however, to a remarkably simple molecule, nitric oxide. Nitric oxide is still an environmental pollutant, suspected carcinogen, and precursor of acid rain, but biologists are looking past its dark side. They now see a molecule that is uniting neuroscience, physiology, and immunology. Its ubiquitous distribution in the body and its multifaceted roles are revising our understanding of how cells communicate and protect themselves. This report examines nitric oxide's role in physiology and pathophysiology and reviews novel therapeutic approaches which involve inhibition or induction of the activity of endogenous nitric oxide. PMID- 8366175 TI - Sotalol: a novel beta-blocker with class III anti-arrhythmic activity. AB - Initially synthesized in 1960, sotalol is a novel beta-adrenoreceptor blocking agent that also possesses class III anti-arrhythmic properties. The drug's ability to lengthen repolarization and prolong effective refractory periods in all cardiac tissues in addition to its beta-blocking effects make sotalol an attractive agent for use in a variety of supraventricular and ventricular arrhythmias. PMID- 8366176 TI - Pharmacokinetics of cyclosporine and steady-state aspirin during coadministration. AB - Anecdotal reports from clinical trials assessing the use of cyclosporine in the treatment of rheumatoid arthritis suggest an association between enhanced renal impairment and combined use of cyclosporine with nonsteroidal anti-inflammatory drugs. To explore possible pharmacokinetic contributions to this phenomenon, a randomized, two-period crossover investigation was performed in 24 healthy volunteers in which a single oral dose of 300 mg cyclosporine was administered alone and on day 10 of multiple oral dosing of aspirin 960 mg three times daily. Serial blood samples were obtained over 48 hours after each cyclosporine dose and over a steady-state dosing interval for aspirin on day 9 (aspirin alone) and day 10 (coadministration of cyclosporine and aspirin). Cyclosporine whole blood concentrations were determined by a specific monoclonal radioimmunoassay and plasma concentrations of acetylsalicylic acid and metabolites by high-performance liquid chromatography. Lack of a pharmacokinetic interaction was conclusively demonstrated for the rate and extent of cyclosporine and acetylsalicylic acid absorption and for the rate and extent of salicylic acid formation after a single dose of cyclosporine was coadministered during steady-state aspirin dosing. If a clear association between enhanced renal impairment and the combined use of cyclosporine and aspirin is substantiated, the underlying mechanism appears to be pharmacodynamic rather than pharmacokinetic. PMID- 8366177 TI - Pharmacokinetics of azathioprine after repeated oral and single intravenous administration. AB - The pharmacokinetics of azathioprine (AZN) were examined in 28 renal transplant patients treated orally with 25 to 150 mg AZN once daily in combination with cyclosporin A and prednisone, and after single intravenous (IV) injection of 5 mg/kg AZN using the rabbit as an in vivo model. The steady-state concentrations of AZN observed in these patients ranged from 6 to 583 micrograms/L, and the interday coefficients of variation of the concentration in three randomly selected patients were 38%, 12%, and 4.6%. The frequency distribution pattern of the apparent oral clearance (TCLor) of AZN separates the patients almost equally into poor (TCLor = 0.126 to 4 L/hour.kg) and extensive metabolizers (TCLor = 5 to 12 L/hour.kg). The data obtained from the IV administration displayed the two compartment model characteristics with mean (standard error of the mean) of alpha, beta, Vc, and total body clearance of 15.3 (2)/hour, 2.38 (.64)/hour, 1.05 (.3) L/kg, and 8.12 (1.26) L/hour.kg, respectively. The large variability in the pharmacokinetic parameters of AZN in patients and even in rabbits under carefully controlled conditions that may be ascribed to the complexity of its metabolism necessitates a careful approach to its dose selection. PMID- 8366178 TI - Pharmacokinetics and dialyzability of sulindac and metabolites in patients with end-stage renal failure. AB - Sulindac was administered as a single 300-mg oral dose to six patients with end stage renal failure and six normal subjects. Plasma concentrations of sulindac and its sulfide and sulfone metabolites were examined over a 48-hour period. As determined by ultrafiltration methods at 37 degrees C, the percentage free of sulindac and sulindac sulfide in plasma was greater, respectively, in the patients with renal failure (10.50 +/- 2.42 and 9.96 +/- 1.21) than in the normal subjects (6.78 +/- 0.45 and 6.01 +/- 0.37). Free sulindac plasma concentrations were not different between the two groups. However, sulindac sulfide, total and free, plasma concentrations were substantially decreased in the group with renal failure. Total area under the curve (AUC) of the sulfide metabolite was 18% in the normal subjects and the free AUC was 29%. In patients with renal failure, the apparent half-lives of sulindac (1.98 +/- 0.76 hours) and sulindac sulfide (15.6 +/- 5.8 hours) were not different from those of normal subjects. Sulindac sulfone half-life was highly variable and longer in the patient group. Studies of dialysis clearance showed that sulindac and its metabolites are poorly dialyzed. A 4-hour dialysis period increased the plasma binding of both sulindac and sulindac sulfide in the patient group. Based on the decreased plasma concentration of the active sulindac sulfide metabolite in the patient group, dosage adjustments may be required in patients with end-stage renal failure. PMID- 8366179 TI - Echocardiograms during six hours of bedrest at head-down and head-up tilt and during space flight. AB - Left ventricular end-diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6-hour bedrest model of 0 gravity (G; 5 degrees head-down tilt) were compared with those of fractional gravity loads of 1/6 G, 1/3 G, and 2/3 G by using head-up tilts of 10 degrees, 20 degrees, and 42 degrees, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two-dimensional and M-mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P < .05) for all tilt angles when compared with control. Ejection fraction (EF) at -5 degrees was greater than at +20 degrees and +42 degrees (not significant); EF at +10 degrees was greater than at +42 degrees (not significant). For the tilt angles of -5 degrees, +10 degrees, and +20 degrees, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20 degrees) by 6 hours (not significant). At the +42 degrees angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366180 TI - Contrasting effects of pyrazinoylguanidine and hydrochlorothiazide in patients with renal insufficiency. AB - A single blind crossover study with washout phases showed that pyrazinoylguanidine (PZG) reduced elevated serum concentrations of urea, triglycerides, and cholesterol in patients with renal insufficiency. Pyrazinoylguanidine was saluretic, without affecting serum potassium or glucose concentrations. The onset of PZG's antihypertensive effect occurred within 4 hours. In contrast, hydrochlorothiazide (HCTZ) increased serum concentrations of urea, triglycerides, and glucose, without affecting cholesterol. PMID- 8366181 TI - Determination of gentamicin pharmacokinetics by bioelectrical impedance in critically ill adults. AB - This investigation compares the accuracy of calculating gentamicin pharmacokinetic parameters by a noninvasive body composition technique (bioelectrical impedance analysis; BIA) with an empiric method, against the two point method as the criterion standard. A prospective concurrent open label design was used. The 32 medical and surgical intensive care unit beds at Henry Ford Hospital, a not-for-profit, university-affiliated teaching hospital, served as the setting. Twenty critical ill adults, Therapeutic Index Scoring System (TISS) = 4, who required gentamicin as part of their normal course of therapy for gram-negative bacillary infections, were evaluated. Gentamicin Vd and k were calculated by three methods. After measurement of body composition parameters by BIA, previously derived gentamicin dosing equations were used to predict gentamicin volume of distribution (Vd) and elimination rate constant (k) (BIA method). Empiric estimates of these parameters (Vd = 0.3L/kg and k derived from creatinine clearance) were compared with the BIA parameters against a criterion standard Vd and k determined from a two-point sampling of gentamicin serum concentrations. Measurements of BIA parameters and gentamicin serum concentrations were made in duplicate with coefficients of variation, < or = 2% and < or = 3%, respectively. The BIA and empiric methods produced resultant pharmacokinetic parameters (Vd and k) not different than those measured by the two-point method. There were no statistically significant differences in mean error (bias), or mean squared error (precision) for both Vd and k assessed by the empiric or BIA methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366182 TI - Effect of time of food administration on the bioavailability of didanosine from a chewable tablet formulation. AB - The effect of the time of food administration on the bioavailability of didanosine, administered as a 300-mg dose of a chewable tablet formulation, was evaluated in 10 men seropositive for the human immunodeficiency virus (HIV), but free of any symptoms of acquired immune deficiency syndrome (AIDS). Using an open, randomized, balanced, incomplete block crossover study design, each patient received the dose of didanosine under four of the five following conditions: (1) after an overnight fast, (2) 30 minutes before a meal, (3) 1 hour before a meal, (4) 1 hour after a meal, or (5) 2 hours after a meal. The meal consisted of a standard high-fat, high-calorie breakfast, consumed over a 15-minute period. Serial blood samples and the total urinary output were collected over a 12-hour interval after each dose for analysis using validated high-pressure liquid chromatography (HPLC)/ultraviolet (UV) methods. Concentration data were used to calculate pharmacokinetic parameters using noncompartmental methods. There were no significant differences among the fasting, 30-minute before, and 1-hour before the meal treatments with respect to maximum peak plasma concentration (Cmax), area under the curve (AUC(0-infinity)), or urinary recovery (%UR). Values for Cmax, AUC(0-infinity), and %UR observed for the 1 and 2 hours after the meal treatments were significantly less than those obtained under either fasting conditions or before the meal. There were no significant differences among any of the treatments with respect to time to reach peak concentration (tmax), half-life (t1/2), or renal clearance (CLR).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366183 TI - Effects of one year of treatment with pravastatin, an HMG-CoA reductase inhibitor, on lipoprotein a. AB - Lipoprotein a [Lp(a)] has emerged as a critical factor in the assessment of cardiovascular risk. In the study reported here, Lp(a) concentrations were monitored in patients taking pravastatin, a new hydrophilic, HMG-CoA reductase inhibitor. A cohort of patients with frozen plasma aliquots at baseline, week 12 of the double-blind therapy, and week 48 of open-label therapy (1 years' treatment) was selected from 306 participants in a phase 2 dose-ranging study of pravastatin. The 125 men and women in the cohort had mean low-density lipoprotein cholesterol (LDL-C) concentrations of at least 150 mg/dL (3.88 mmol/L), and mean plasma triglyceride concentrations less than 250 mg/dL (2.82 mmol/L) during the baseline diet phase. During the double-blind phase, 46 patients received placebo, and 79 received pravastatin 10, 20, or 40 mg daily. Only the 79 pravastatin treated patients in the cohort continued in the 48-week open-label study of pravastatin. During the double-blind phase, Lp(a) decreased 4.6% in patients taking placebo, and 0.4% in patients taking pravastatin. Net change was not significant. At week 48, in the patients taking pravastatin, Lp(a) had increased 2.4%, a difference that again was not statistically significant. Low-density lipoprotein cholesterol (-33.6%), total cholesterol (-25.6%), triglycerides ( 19.9%), high-density lipoprotein cholesterol (HDL-C) (+7.0%), apolipoprotein A-I (+13.3%), and apolipoprotein B (-33.0%) changed significantly (P < .01). Among 19 patients with baseline Lp(a) levels greater than 30 mg/dL, Lp(a) decreased insignificantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366185 TI - New FDA initiatives. PMID- 8366184 TI - Lovastatin does not affect oral glucose tolerance in hypercholesterolemic patients. AB - In 15 non-diabetic Type II hypercholesterolemic patients, the effect of 80 mg lovastatin daily on oral glucose tolerance was investigated. Using a randomized, double-blind, two-panel, parallel design, patients on a low cholesterol diet received lovastatin (n = 7) or placebo (n = 8) for 6 weeks. After 6 weeks of treatment, patients receiving lovastatin had a significant reduction in total cholesterol (30%), LDL-cholesterol (36%), and triglycerides (26%). Time courses of plasma glucose and serum insulin changes from baseline after the oral glucose tolerance test were evaluated by AUC. No statistically significant differences were observed in the AUC of changes from baseline between treatment groups or within either treatment group at prestudy, 6 weeks, and poststudy. No patient had a clinically important laboratory or clinical drug-related adverse effect during the study. This study demonstrated that short-term administration of 80 mg lovastatin daily effectively lowers cholesterol without having adverse effects on oral glucose tolerance. PMID- 8366186 TI - A new extended-release formulation of diltiazem HCl for the treatment of mild-to moderate hypertension. AB - Calcium-channel blockers are a safe and effective treatment modality and have been used extensively in the treatment of angina and hypertension. Dilacor XR capsules, a new extended-release formulation of diltiazem, has been developed for the treatment of hypertension. Dilacor XR (Rhone-Poulenc Rorer Pharmaceuticals Inc., Collegeville, PA) uses a novel drug delivery system, the Geomatrix (JAGO Research AG, Zollikon, Switzerland) controlled-release system, to deliver diltiazem at a constant rate for 24 hours. The rate of absorption is also slower. As doses of Dilacor XR were increased from 120 mg to 540 mg/day, there were disproportionate increases observed in area under the curve, maximum peak plasma concentration, minimum peak plasma concentration, and average peak plasma concentration. The efficacy data from two clinical trials have confirmed the established efficacy of diltiazem and the 24-hour efficacy of Dilacor XR in the control of mild-to-moderate hypertension. The incidence of adverse effects with Dilacor XR in doses as high as 540 mg/day was generally comparable to that of placebo. This new extended-release formulation of diltiazem should significantly facilitate blood pressure control because of better patient compliance with a once daily regimen. PMID- 8366187 TI - Efficacy of class 1C antiarrhythmic agents in patients with inducible ventricular tachycardia refractory to therapy with class 1A antiarrhythmic drugs. AB - The efficacy of class 1C antiarrhythmic agents was determined in 36 patients with inducible sustained monomorphic ventricular tachycardia during baseline electrophysiology study (EPS), who continued to have inducible monomorphic ventricular tachycardia during EPS on class 1A antiarrhythmic therapy. Of 12 patients who partially responded to class 1A drugs, 11 (91.7%) continued to have a partial response during EPS on class 1C therapy, whereas one patient did not respond. Of 24 nonresponders to class 1A therapy, 2 (8.3%) responded during EPS on class 1C therapy, 7 (29.2%) partially responded, and 15 (62.5%) did not respond. In the 24 nonresponders to class 1A therapy, 9 of 17 patients (53%) with left ventricular ejection fraction (EF) > or = 30% responded or partially responded to class 1C therapy, compared with none of 7 patients with EF < 30% (P < .05). The EPS on class 1C agents in patients who fail to respond to class 1A therapy may be warranted only in those with EF > or = 30%. PMID- 8366188 TI - Pharmacodynamics and dose-response relationship of famotidine: a double-blind randomized placebo-controlled trial. AB - The dose-response relationship of oral famotidine at doses up to 10 mg was evaluated in 10 healthy male subjects to assess the extent and duration of inhibition of meal-stimulated intragastric acid secretion. Each subject received single oral administrations of famotidine 0.5, 2.5, 5.0, and 10.0 mg and placebo in a double-blind, randomized, cross-over fashion. Intragastric pH was measured every 4 seconds for 24 hours and expressed as the mean pH for each 10-minute interval. Standard high-protein meals were provided 1 hour before each dose of study drug and at 3 and 9 hours postdose. The mean intragastric pH was significantly higher after famotidine doses 2.5, 5.0, and 10.0 mg than after placebo at times 2.5 to 3.0, 1.8 to 3.2, and 1.7 to 4.2 hours postdose, respectively. There were no significant differences in mean pH seen between famotidine 0.5 mg versus placebo. The range of the pH means between 1.7 and 3.2 hours postdose was placebo (1.0 to 1.3), famotidine 0.5 mg (1.1 to 1.4), 2.5 mg (1.4 to 1.7), 5.0 mg (1.7 to 2.1), and 10.0 mg (2.0 to 2.3). There was a statistically significant linear dose-response relationship between famotidine dose and intragastric pH between 1.7 and 3.8 hours and from 6.3 to 8.7 hours after ingestion. PMID- 8366189 TI - Nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) in women and obese men compared with normal-sized men. AB - This study examined the effect of gender and body weight on the pharmacokinetic properties of the Nicotine Transdermal System (NTS) (Nicoderm). This NTS was applied for 24 hours to 13 normal-sized men, 13 women, and 13 obese men, all of whom were smokers who had abstained from cigarettes for the previous 24 hours. Pharmacokinetic parameters were determined during a single application of the system. The mean nicotine maximal plasma concentration (Cmax) and area under the curve (AUC) values for women did not differ significantly from those for normal sized men. Nicotine Cmax and AUC values, however, were significantly lower in obese compared with normal-sized men; nicotine AUC was strongly correlated to body weight and body mass index. Mean apparent nicotine elimination rate constant values were not significantly different between normal-sized and obese men, but the apparent elimination rate constant value was significantly higher in women. The possible clinical significance of the differences in nicotine AUC values with body weight is discussed. PMID- 8366190 TI - Presystemic extraction: mechanisms and consequences. AB - Many drugs have incomplete systemic availability after oral dosage. This can be attributed to incomplete absorption from the gastrointestinal tract, or to presystemic extraction, in which a fraction of an orally administered dose is biotransformed before reaching the systemic circulation. Presystemic extraction can occur either via biotransformation by gastrointestinal mucosa or enteric flora, or via metabolism during the "first-pass" through the liver. For drugs with low oral bioavailability due to high presystemic extraction, impaired clearance leads to increased peak plasma levels and greater area under the concentration-time curve, but minimal change in elimination half-life. PMID- 8366191 TI - The hepatic first-pass metabolism of problematic drugs. AB - The first-pass hepatic metabolism of a number of important therapeutic agents is inconsistent with traditional models that assume that the hepatic extraction ratio of a drug is constant in each individual (independent of the concentration of drug in the hepatic sinusoidal blood and also independent of the history of exposure to the drug). In this review, the authors examine the first-pass metabolism of five "problematic drugs" (propranolol, lidocaine, propafenone, verapamil, and nitroglycerin). Each of these compounds has unique facets to its hepatic clearance and pharmacokinetics as well as striking similarities. Selected aspects of first-pass metabolism are reviewed, and a theory that may explain some of the unusual behavior of the four lipophilic bases (propranolol, lidocaine, propafenone, and verapamil) is presented. Finally, the unusual and variable clearance of nitroglycerin is discussed. PMID- 8366192 TI - The clinical implications of first-pass metabolism: treatment strategies for the 1990s. AB - The first-pass effect is real. It may pose obstacles to the treatment of disease, and strategies need to be developed to address the problem that first pass can cause. First we have to look at identifying the problem, and this symposium has helped to further emphasize that the problem exists and awareness is increasing. The first-pass effect has been a basic tenant of pharmacology but an area not receiving active research interest and one that is often overlooked in the clinical arena. Avoiding drug interactions is a consideration, and that is a major challenge to the field of clinical pharmacology. Clinicians need to be aware of the problem, aware of the danger areas with drugs, and first pass. Another alternative is to turn to chemical modification of a drug that avoids needing to take first pass into consideration. PMID- 8366193 TI - Development of blobs in the visual cortex of macaques. AB - We have examined the area of the primary visual cortex and the number and size of blobs within it in 10 neonatal and 11 adult rhesus monkeys. The average area of the primary visual cortex (V1) increases from 919 mm2 in newborns to 1,069 mm2 in adult animals (16%). The number of blobs decreases per unit area from an average of 5.2/mm2 at birth to 4.3/mm2 in maturity (18%). As a consequence, the number of blobs remains approximately the same during maturation, at about 4,800/hemisphere. These observations correct a preliminary report on a subset of the animals studied here (Purves and LaMantia: Proc Natl Acad Sci 87:5765, '90), in which it appeared that blob number might increase between birth and maturity. As in other regions of the developing postnatal brain, we found no net loss of modular circuitry. PMID- 8366194 TI - Localization of sulfated glycoprotein-2/clusterin mRNA in the rat brain by in situ hybridization. AB - Sulfated glycoprotein-2 (SGP-2) gene expression seems to be constitutively expressed in a variety of tissues and organs, although levels of expression vary widely from one tissue to the other. SGP-2, also known as clusterin, has been reported to be expressed in the central nervous system (CNS). Some possible roles for brain SGP-2 have been postulated. In order to provide a substrate for a better understanding of the functions of this glycoprotein in the CNS, we investigated the detailed anatomical and cellular distribution of SGP-2 mRNA in the adult rat brain as well as the variation in its cellular expression after excitotoxin lesion. Transcripts for SGP-2 were found to be distributed throughout the rat CNS, although regional differences in their prevalence were readily observed. The ependymal lining of the ventricles showed the highest level of expression followed by various gray matter areas, some of which contained very intensively labeled cells. These cells were mostly found among several hypothalamic and brainstem nuclei, the habenular complex, as well as in the ventral horn of the spinal cord, which displayed striking hybridization signals over motoneurons. Occasional cells expressing high levels of SGP-2 transcripts were found in fiber tracts. Highly SGP-2 mRNA-positive resting glial cells were mainly located near the glial limitans and blood vessels. Two areas of relatively low constitutive SGP-2 mRNA expression are shown to produce strong hybridization signals 10 days after the local administration of the excitotoxin kainic acid. This overexpression of SGP-2 transcripts appears to involve GFAP-positive cells. Taken together, these results indicate that in the intact adult rat CNS, various cell populations, including neurons, constitutively express SGP-2 transcripts, whereas in the injured brain, reactive astrocytes become the major producers. PMID- 8366195 TI - Neuronal morphology and efferent projections of the dorsal nucleus of the lateral lemniscus in the rat. AB - The dorsal nucleus of the lateral lemniscus (DLL) is the main source of inhibitory influence in the auditory brainstem of mammals. The cytoarchitecture and connectional properties of DLL were established in the cat in contrast to the rat. The goal of the present study was to establish to what extent the anatomical properties of the rat DLL compare to those of the cat, thus providing a basis of interpretation for future functional studies in the rat, an animal model used more and more in the auditory system. DLL of the rat contains four well differentiated neuronal types, as seen in Nissl-stained material. Type I neurons are large and multipolar with abundant cytoplasm and darkly stained Nissl substance. Type II neurons are large, bipolar and darkly stained in Nissl material. Type III neurons are medium in size and their soma is round or ovoid. Type IV neurons are small and round with scant cytoplasm; they seem to be also the least common neuronal type of the DLL. After Phaseolus vulgaris leucoagglutinin or biocytin injections in the DLL, fibers and terminals labeled by orthograde transport were observed in the corresponding region of the contralateral DLL and in the inferior colliculus, bilaterally. A few labeled fibers and terminal fields were seen in the deep layers of the superior colliculus bilaterally, as well as in the medial division of the medial geniculate body and, even more rostrally, in the posterior nucleus of the thalamus. Descending projections from DLL terminated in the periolivary regions of the ipsilateral superior olivary complex. Retrograde tracing based on injections of horseradish peroxidase in the various targets of the DLL confirmed the connections established with orthograde labeling. PMID- 8366196 TI - Experimentally induced visual projections to the auditory thalamus in ferrets: evidence for a W cell pathway. AB - We have previously reported that following specific neonatal brain lesions in ferrets, a retinal projection is induced into the auditory thalamus (Sur et al., Science 242:1437, '88). In these "rewired" ferrets, a novel visual pathway is established through auditory thalamus [the medial geniculate nucleus (MGN)] and primary auditory cortex (A1); cells in both MGN and A1 are visually responsive and exhibit properties similar to those of visual cells in the normal visual pathway. In this paper, we use three approaches--physiological, anatomical, and developmental--to examine which of the retinal ganglion cells project to the MGN in these rewired ferrets. We find that: 1) physiological response properties of postsynaptic visual cells in the MGN are W-like; 2) retinal ganglion cells back filled from the MGN are small and similar to soma sizes of subsets of the normal retinal W cell population; and 3) subpopulations of these small cells can be preferentially rerouted to the MGN in response to different surgical manipulations at birth, consistent with differential W cell projection patterns in normal animals. These data suggest that retinal W cells come to project to the MGN in rewired animals. These findings not only provide a basis on which to interpret functional properties of this novel visual pathway, but also provide important information about the developmental capabilities of specific retinal ganglion cell classes and the regulation of their projections by target structures in the brain during development. PMID- 8366197 TI - Distribution of GABA-immunoreactive nerve fibers and cells in the cervical and thoracic paravertebral sympathetic trunk of adult rat: evidence for an ascending feed-forward inhibition system. AB - Neurochemical and immunohistochemical evidence suggests that the superior cervical ganglion (SCG) contains all components of a gamma-aminobutyric acid (GABA)ergic transmission system, which includes GABAergic axons of unknown origin. The number of nerve fibers with and without GABA-like immunoreactivity was determined in interganglionic connectives at all cervical and thoracic levels of the paravertebral sympathetic trunk. In addition, the distribution of GABA immunoreactive (IR) neurons was established within the ganglion chain and compared with the relative frequency of principal neurons richly innervated by GABA-IR axon terminals. The following results were obtained: 1) the total number of nerve fibers in cross sections did not significantly vary between the cervical levels, but it increased steadily from upper to lower thoracic segments; 2) in contrast, the number of GABA-IR fibers decreased from the cervical sympathetic trunk below the SCG (approximately 300 fibers) down to the seventh to tenth thoracic ganglion, below which no such fiber was seen; 3) GABA-IR nerve fibers originate from a subclass of GABA-IR cells; these are small, bipolar neurons with predominantly ascending, unmyelinated axon-like processes; 4) the number of principal neurons richly innervated by GABA-IR nerve fibers decreased from the SCG to the upper thoracic ganglia, and was very small below; and 5) apart from basket-like innervation, GABA-IR axons also formed diffuse networks around GABA negative principal neurons predominantly in cervical and upper thoracic ganglia. These data suggest that the GABAergic innervation of paravertebral sympathetic ganglia is more complex than previously suspected. What appears as preganglionic afferents from several spinal segments (C8-Th7) innervate GABAergic neurons in the sympathetic trunk which have ascending axons and focus their inhibitory effects on the cervical sympathetic ganglia, predominantly the SCG. These data suggest that GABAergic small interganglionic neurons form a feed-forward inhibition system, which may be driven by multisegmental spinal input in the paravertebral sympathetic ganglion chain. PMID- 8366199 TI - Qualitative and quantitative analyses of the patterns of retinal input to neurons in the dorsal lateral geniculate nucleus of the cat. AB - In the visual system of the cat the projection from the retina to the lateral geniculate nucleus has been studied extensively. However, the patterns of synaptic contacts made by individual axons onto individual cells have not been described. In this study these patterns have been examined for class 1 cells (Guillery: J Comp Neurol 128:21, '66). Retinogeniculate axons and lateral geniculate neurons are labeled with horseradish peroxidase (HRP) via injections into the optic tracts and optic radiations, respectively. Sections are then processed for combined light and electron microscopic analysis. They are examined with the light microscope to identify labeled lateral geniculate neurons that appear to be contacted by labeled retinal axons. These cells and axons are then analyzed by a computerized microscope system, and sites of apparent synaptic contact are recorded. This light microscopic analysis indicates that individual class 1 cells are contacted by many retinogeniculate axons (> 10) and that each of these axons contacts many lateral geniculate neurons (> 20). Some axons make numerous contacts that are concentrated onto a few dendrites, while others make only a few contacts, which are spread over several dendrites. In all cases, the majority of contacts are on the dendritic shafts of relatively thick secondary and tertiary dendrites. Electron microscopic analysis confirms that most of the contacts identified with the light microscope are synaptic. It also reveals that labeled and unlabeled retinal axons can innervate the same dendritic segment. Finally, one cell was studied that had its soma and most of its dendrites in lamina A1 but some of its dendrites extended into lamina A. This cell received input from retinal axons in both layers, thus suggesting that it may have been binocularly excitable. PMID- 8366198 TI - Distribution of luteinizing hormone-releasing hormones I and II (LHRH-I and -II) in the quail and chicken brain as demonstrated with antibodies directed against synthetic peptides. AB - Polyclonal antibodies were raised in rabbits against polypeptides corresponding to the N-terminal part (heptapeptides) of the two avian gonadotropin-releasing hormones, chicken (c) LHRH-I and -II. These peptides, which were synthesized by the continuous-flow technique, were selected because they contained the smallest number of common amino acid residues. The pGlu-His-Trp-Ser sequence at the C terminal was suppressed to avoid possible cross-reactions between the antisera. The antisera generated in this way were tested for specificity by solid and liquid phase absorption as well as by antigen spot tests. The antiserum raised against cLHRH-I recognized this peptide preferentially though not exclusively. Some cross-reaction with cLHRH-II was observed in the absorption test, although spotting tests suggested a total specificity. The anti cLHRH-II appeared to be completely specific in all tests. These two antibodies were then used to study the distribution of cLHRH-I and -II immunoreactive structures in the quail and chicken brain. cLHRH-I immunoreactive perikarya were observed in a fairly wide area covering the preoptic-anterior hypothalamic and septal region. By contrast, cLHRH-II cells were confined to a single group located in the dorsal aspects of the occulomotor nuclei, at the junction of the di- and mesencephalon. A sex difference in the number of cLHRH-I cells was detected in the anterior lateral preoptic region of the quail. Fibers immunoreactive for either cLHRH-I or cLHRH II were widely distributed in the telencephalon, diencephalon, and mesencephalon but showed a specific pattern of anatomical localization. In particular, a high density of cLHRH-I fibers were seen in the external layer of the median eminence, while cLHRH-II fibers were less prominent at this level. Contrary to previous reports, a significant amount of cLHRH-II fibers were however seen throughout the median eminence (mostly external layer). The extensive distribution of both cLHRH I and -II fibers in the quail and chicken brain is consistent with the potential role played by these peptides in the gonadotropin secretion and in the control of reproductive behavior. The specific role of cLHRH-II remains however elusive at present. PMID- 8366200 TI - The eosinophil. PMID- 8366201 TI - Different cytogenetic findings in two clinically similar leukaemic dogs. AB - A 4-month-old German Shepherd puppy and a 7-year-old Boxer dog, in which a clinical diagnosis of acute lymphoblastic leukaemia had been made, were investigated cytogenetically. In the puppy a diploid karyotype was found, but the malignant clone in the Boxer was characterized by an extra metacentric chromosome, apparently formed as the result of a Robertsonian translocation of two chromosomes 1. These findings are discussed against the background of similar cases reported in the literature. Possibly, different types of acute canine leukaemic disease, occurring at different ages, can be distinguished by cytogenetic evaluation. PMID- 8366203 TI - Laminin and type IV collagen in experimental rat oral carcinomas. AB - The pattern of staining and the distribution of laminin and type IV collagen in normal rat tongue mucosa and induced tongue carcinomas were investigated by immunohistochemical techniques. Both normal and neoplastic epithelial basement membrane revealed positive staining for laminin and type IV collagen. However, compared with normal tissue, carcinomas exhibited areas of increased density and thickness for laminin. Focal tumour basement membrane discontinuities were observed in some specimens stained for type IV collagen. PMID- 8366202 TI - Ultraviolet radiation-induced corneal tumours in the South American opossum, Monodelphis domestica. AB - Chronic exposure of the South American opossum, Monodelphis domestica, to ultraviolet radiation (UVR) induced 154 primary tumours of the cornea in 152 eyes. Tumours developed gradually; frank neoplasia was preceded by non-neoplastic proliferation of corneal stromal fibroblasts (keratocytes) and extensive neovascularization. Histologically, the majority of tumours (134 of 154) appeared to be fibrosarcomas arising from keratocytes, but about 12 per cent of the tumours (18 of 154) had a highly vascular appearance, suggesting haemangiosarcoma. In two eyes, squamous cell carcinomas overlay mesenchymal tumours. Ultrastructural features of UVR-induced corneal tumours were consistent with tumours, and cultured skin fibroblasts expressed high content of messenger RNA for the intermediate filament vimentin; no cytokeratin messenger RNA was detected in these cells and cell lines. Based upon their light microscopic, ultrastructural, and intermediate filament biosynthetic characteristics, the majority of UVR-induced corneal tumours in M. domestica appeared to be fibrosarcomas. Haemangiosarcomas constituted a smaller proportion of the tumours, and squamous cell carcinomas were very rare. PMID- 8366204 TI - Ultrastructural features of normal epithelium and 4-nitroquinoline 1-oxide induced carcinomas of the rat tongue. AB - An electron microscopical examination of normal rat lingual mucosa and 4 nitroquinoline 1-oxide (4NQO)-induced tongue carcinomas was undertaken. In normal rat tongue, the epithelium of papillae and interpapillary regions exhibited two distinct keratohyalin granule types and essentially similar ultrastructural cellular features in the different epithelial compartments. The interface between epithelium and connective tissue showed a continuous basal lamina. Compared with normal rat tongue epithelium, 4NQO-induced oral carcinomas revealed cellular and nuclear pleomorphism, atypical tonofilament aggregates, increased and swollen mitochondria, dilated intercellular spaces, local discontinuities and thickening of the basal lamina. PMID- 8366205 TI - Pathology and epidemiology of canine distemper in raccoon dogs (Nyctereutes procyonoides). AB - From September to December 1991, a large number of free-ranging raccoon dogs (Nyctereutes procyonoides) died from a highly contagious disease in the vicinity of Tokyo. Eighteen seriously ill or dead animals were submitted for necropsy. The pathological findings resembled those in a masked palm civet (Paguma larvata) found infected with canine distemper virus (CDV) in the same area in late August 1991. The most striking features were pneumonia and gastroenteritis. Microscopical lesions consisted of cytoplasmic and intranuclear eosinophilic inclusion bodies in various organs and tissues, bronchiolointerstitial pneumonia, non-suppurative demyelinating encephalitis, lymphocytic depletion in various lymphoid tissues and catarrhal or necrotizing gastroenteritis. CDV-specific antigens, demonstrated immunohistochemically in the epithelial tissues, central nervous system and lymphoid tissues, corresponded with the presence of the eosinophilic inclusion bodies in sections of the same lesions stained with haematoxylin and eosin. Ultrastructurally, both cytoplasmic and intranuclear inclusion bodies were observed to be composed of aggregates of viral nucleocapsids. The study provided clear evidence that CDV was the cause of the disease. It is possible that the masked palm civet introduced the infection into the raccoon dog population. PMID- 8366206 TI - Two haemangioendotheliomas in a bovine brain. AB - The microscopical, ultrastructural and immunohistochemical features of an unusual type of haemangioendothelioma in the brain of a calf are described. The salient features of this tumour were an exuberant proliferation of vasoformative elements whose endothelial cells exhibited epithelioid and spindle cell features. Intracytoplasmic miniature lumen formation in endothelial cells was characteristic of this vascular neoplasm. PMID- 8366207 TI - Cerebral healing after craniotomy to evacuate a Coenurus cerebralis cyst. AB - An 11-month-old ewe developed neurological signs caused by a space-occupying lesion in the left cerebral hemisphere. Successful surgical evacuation of a Coenurus cerebralis cyst was carried out, the neurological signs regressed and the ewe produced twins in the following breeding season. Sixteen months after the surgical treatment the ewe was found dead and necropsy revealed a vegetative endocarditis. In the brain, at the site of cyst evacuation, there was a collapsed subcortical cavity lined by siderotic fibrovascular tissue and surrounded by a modest glial reaction. These observations confirm that the clinical signs of cerebral coenuriasis are related to the space-occupying effect of the parasitic cyst and indicate that partial replacement by gliomesodermal tissue plays a part in healing of the collapsed cyst. PMID- 8366208 TI - Argyrophil cells in gastrointestinal epithelial tumours of the dog. AB - Fifty-two cases of gastrointestinal mucosal tumours of the dog were examined for argyrophil cells by means of the Grimelius stain. Argyrophil cells were found in each of five cases (100 per cent) of gastric adenoma, in five (71.4 per cent) of seven large-intestine adenomas, in 13 (59.1 per cent) of 22 gastric carcinomas, in five (62.5 per cent) of eight small-intestine carcinomas and in four (40 per cent) of ten large-intestine carcinomas. The argyrophil cells represented a minority of the tumour cell population in all cases. These results demonstrate that a significant proportion of gastrointestinal mucosal tumours of the dog contain a mixture of epithelial and endocrine cells. Similar findings have been reported in man. PMID- 8366209 TI - Microscopical characteristics of uterine wall arteries in barren aged mares. AB - The morphology of the arteries in the uterine wall was studied in three multiparous aged mares that had suffered repeated pregnancy failure. The uterine wall arteries exhibited elastosis of the intima or adventitia, or both, resembling "physiological pregnancy sclerosis". In areas affected by elastosis, degeneration of the pre-existing elastic fibres and increased glycosaminoglycans were frequently observed. Newly formed elastic fibres were not evident. Delayed resorption due to disordered metabolic turnover of the elastin was thought to be an important factor in the pathogenesis of the arterial elastosis in the uterine wall. PMID- 8366210 TI - Paraneoplastic pemphigus: a subset of patients with pemphigus and neoplasia. AB - We reviewed the clinical, histologic, and immunofluorescence features of 20 patients with pemphigus and neoplasia and compared them with a control group of 17 patients with pemphigus without neoplasia. Patients with neoplasia were divided according to clinical, histologic, and immunofluorescence findings into those with paraneoplastic pemphigus syndrome (12 patients) and those with classic pemphigus vulgaris or pemphigus foliaceus with neoplasia (8 patients). The histologic findings in patients with paraneoplastic pemphigus included acantholysis, interface dermatitis, spongiosis, and satellite keratinocyte necrosis. Histologic findings in the 8 patients with classic pemphigus and neoplasia included acantholysis and spongiosis. Direct immunofluorescence in both paraneoplastic pemphigus and pemphigus with neoplasia showed IgG staining of cell surface proteins (intercellular substance) and deposition of immunoglobulin at the basement membrane zone. Indirect immunofluorescence with rat bladder substrate was used to differentiate paraneoplastic pemphigus from classic pemphigus. Circulating IgG anti-cell-surface protein antibodies were detected in 4 patients with paraneoplastic pemphigus syndrome; they were absent in 2 patients with pemphigus and neoplasia. Immunoprecipitation of sera from the 4 patients with epithelial staining showed the complex of bands identified in studies of paraneoplastic pemphigus syndrome. We conclude that paraneoplastic pemphigus syndrome has distinct clinical, histologic, and immunologic features that differentiate it from classic pemphigus with underlying neoplasia. PMID- 8366211 TI - DNA ploidy of basal cell carcinoma determined by image cytometry of fresh smears. AB - Image analysis of nuclear DNA content (DNA ploidy) was performed on smears of basal cell carcinoma (BCC) obtained during Mohs microscopically-controlled surgery from 51 tumors. DNA ploidy was compared with histologic growth pattern and the contour of the invading edge. There was a statistically significantly increased frequency of DNA aneuploidy in smears from BCC exhibiting partial or total diffuse (infiltrative and superficial multicentric) growth patterns (80%; 32 of 40) as compared to solely circumscribed growth patterns (0%; 0 of 11) (p < 0.001). PMID- 8366212 TI - Primary cutaneous phaeohyphomycosis: report of seven cases. AB - We report seven cases of primary cutaneous phaeohyphomycosis. There were five males and two females, ranging in age from 42-65 years (mean 57.7 years). Two patients were otherwise healthy, but five were immunocompromised. One patient had rheumatoid arthritis and was on oral prednisone; two were renal transplant recipients, one was a heart transplant recipient, and the fifth had dermatomyositis. No history of trauma was elicited from any of the patients, but in two cases, foreign material was seen in the tissue sections. All lesions were on the extremities. In two cases, tissues were cultured, and these grew Exophiala jeanselmei. The others were not cultured because fungal infection was not clinically suspected. No systemic disease developed in any of the cases, and all were cured by the simple, complete excision of the lesions. PMID- 8366213 TI - Histological and ultrastructural study of a family with erythrokeratodermia progressiva symmetrica. AB - We have examined a family with 4 members in three succeeding generations suffering from a severe keratinization disorder. The clinical phenotype, with symmetric plaques on the extremities, corresponded to erythrokeratodermia progressiva symmetrica. It was manifested at birth, however, and in addition to the hyperkeratotic plaques, follicular hyperkeratosis was also observed. Electron microscopy revealed multiple morphological changes such as myelinated membrane structures, or needles, which were similar to those occurring in ichthyotic disorders and tyrosinemia, as well as in harlequin fetuses, all of which were excluded clinically or biochemically in our patients. PMID- 8366214 TI - CD44 expression in normal and inflamed skin. AB - CD44 is the principal cell surface receptor for hyaluronate. In non-inflamed skin, CD44 expression is limited to the cell membrane of eccrine coil cells. The distribution on these cells is asymmetric, with intense staining on the dermal side and little staining on the luminal side of the coil cell. In skin containing a pathologic process, either inflammatory or neoplastic, CD44 expression can be widespread on the membranes of keratinocytes and on infiltrating lymphocytes in the vicinity of the process. Diverse roles have been proposed for CD44 and largely involve aspects of cellular adhesion in one setting or another. CD44 may identify a more mobile, proliferating keratinocyte that is responding to local injury. In eccrine coil, the stable presence of CD44 on the non-luminal surface of secretory cells indicates an undefined function for CD44 in the generation of eccrine sweat. PMID- 8366216 TI - Human subcutaneous pythiosis. AB - Two cases of subcutaneous infection caused by the primitive aquatic hyphal organism Pythium are described. Pythium is an important pathogen of horses in the U.S.A. and Australia. Cases of human subcutaneous pythiosis have been cited in the literature, but clinical and histopathological features have not been described previously. Both cases occurred in young immunocompetent males in the periorbital region and showed rapid growth, clinically mimicking a tumor and requiring operative biopsy. In both cases there was a history of exposure to either swampy water or horses. The tissue reaction was distinctive, closely resembling that seen in equine pythiosis, comprising well-defined granular eosinophilic islands bordered by macrophages, multinucleate giant cells, fibrosis and numerous eosinophils. Hyphae were well demonstrated with the Grocott stain but only poorly with the PAS method. Identity of the organisms was confirmed with an immunoperoxidase technique employing a polyclonal antiserum to Pythium. Both patients responded well to amphotericin B. PMID- 8366215 TI - Localization of MGSA/GRO protein in cutaneous lesions. AB - Melanoma growth stimulatory activity (MGSA/GRO), a cytokine originally characterized as an autocrine growth factor for melanoma cells, is highly chemotactic for neutrophils and releases neutrophil elastase as well as other matrix-degrading enzymes. Previous work has demonstrated the presence of MGSA/GRO in melanocytic lesions and in the epidermal keratinocytes of non-lesional skin and psoriatic scale. Herein, MGSA/GRO localization was examined in a variety of human skin lesions exhibiting proliferative and/or differentiative disorders using immunohistochemical methods. Most lesions showed greater MGSA/GRO immunoreactivity in the more differentiated suprabasal keratinocytes of the stratum spinosum and stratum granulosum than in the stratum basalis, where the dividing basal cells are found. Hair follicles, sebaceous glands, and sweat glands were also frequently positive for MGSA/GRO. The highest level of immunoreactive MGSA/GRO in diseased epidermis was detected in verruca vulgaris, followed by psoriasis, keratoacanthoma, and squamous cell carcinoma. Detection of MGSA/GRO in basal cell carcinoma was variable, being present in the sclerosing variant and absent in the more common nodular variant. Melanocytic lesions stained less intensely for MGSA/GRO than keratinocytic lesions, where the levels of MGSA/GRO expression correlated with the inflammatory response and degree of keratinocyte differentiation. PMID- 8366218 TI - The American Society of Dermatopathology. The first thirty years. PMID- 8366217 TI - Carcinosarcoma of the skin: immunohistochemical and electron microscopic observations. AB - A rapidly growing, hemorrhagic, exophytic tumor on the upper back of a 44-year old male patient was investigated. Histological, immunohistochemical, and electron microscopic studies revealed both basal cell carcinoma-like and spindle cell sarcoma-like structures intermingled in the same tumor. Clinical consequences to this patient were mainly dependent on the sarcomatous element. PMID- 8366219 TI - The polymerase chain reaction. Applications in dermatology. AB - Within the space of the last 5 years, application of the revolutionary in vitro method of deoxyribonucleic acid (DNA) amplification known as the polymerase chain reaction (PCR), has become ubiquitous. The rapidly increasing number of clinical and research articles utilizing this technology, both in the dermatologic and general medical literature, requires one to have at least a basic understanding of how the PCR is conducted, what it has to offer, and the potential shortcomings. Such knowledge will hopefully allow a more critical appraisal of an increasingly complex literature. This review aims to describe the methodology and medical applications of this powerful technique with special consideration to the increasing role PCR may have on dermatologic research and practice. PMID- 8366220 TI - Advanced use of tissue adhesive in hair transplantation. AB - BACKGROUND: Cobblestoning is an unsightly result of graft elevation in the recipient site after hair transplantation. OBJECTIVE: To describe the use of tissue adhesives for the avoidance of cobblestoning. RESULTS: The long-term cosmetic appearance of hair transplants may be improved through the use of cyanoacrylate adhesives is the virtual elimination of the common problem of graft elevation or cobblestoning, which produces an unsightly bumpiness in the recipient area. The choice of type of adhesive and the method of application are central to successful use of this technique. CONCLUSION: The indirect benefits of elimination of the need for postoperative bandages and restrictions in activities couple with the cosmetic results to produce a high degree of patient satisfaction. PMID- 8366221 TI - The treatment of advanced Merkel cell carcinoma. A multimodality chemotherapy and radiation therapy treatment approach. AB - BACKGROUND: The optimal management of Merkel cell carcinoma has not been clearly defined. OBJECTIVE: To describe the treatment of eight patients who presented with Merkel cell carcinoma. METHODS: Eight patients with advanced locoregional Merkel cell carcinoma were seen in our institute over a 7-year period. Four patients were successfully treated by induction chemotherapy after excisional biopsy, followed by radiotherapy. Three patients died from widespread metastases and one from neutropenic sepsis induced by chemotherapy. RESULTS: These cases demonstrate the potential lethality and aggressive nature of this rare skin tumor despite its chemosensitive and radioresponsive character. In all four patients who are alive and disease-free, chemotherapy was given first and radiotherapy was given as consolidation. CONCLUSION: We suggest that a multimodality treatment approach--chemotherapy followed by radiotherapy--is indicated in patients with advanced Merkel cell carcinoma. PMID- 8366222 TI - Lateral rhinotomy approach for Mohs micrographic surgery of the anterior septum. AB - BACKGROUND: Neoplasms of the nasal septum and internal alar surface are very difficult to treat. This is because of the complicated surface, proximity to important anatomic structures, and technical difficulty--both to resection and follow up. Mohs micrographic surgery might be the ideal mode of treatment for such tumors; however, it is very difficult to accomplish through the nostril. OBJECTIVE: To resect the tumor on the nasal septum and internal alar surface using Mohs micrographic surgery. METHODS: Lateral rhinotomy was performed as a preparatory stage to Mohs micrographic surgery of the anterior septum and intranasal alar surface. RESULTS: The ala nasi was detached from the cheek, thus exposing the anterior nasal cavity--enabling direct access to the neoplasms and allowing excellent visualization. CONCLUSION: Lateral rhinotomy, as described in this article, is a simple office procedure and in most cases heals with no visible scar. PMID- 8366223 TI - Two new retractors for hair replacement surgery. AB - BACKGROUND: Two new retractors that facilitate scalp reduction and scalp-lifting surgery are introduced. OBJECTIVE: To improve the accuracy, visibility and speed of alopecia reducing procedures. METHODS: These retractors were developed through trial and error in cooperation with the Robbins Instrument Corporation. RESULTS: The suction retractor has been found to clear the field, elevate the scalp flap, and put the skin on stretch simultaneously. The serrated hook retractor has been found to greatly improve visibility for the cauterization of bleeders. The hook and serrated surface of this retractor prevents intraoperative slippage. CONCLUSION: The two new retractors introduced in this article have been found to improve greatly the accuracy, visibility, and speed of alopecia reducing procedures. PMID- 8366224 TI - Pulmonary edema, shunt and blood flow distribution. Problems, progress and perspectives. PMID- 8366225 TI - Dependence of shunt on cardiac output in unilobar oleic acid edema. Distribution of ventilation and perfusion. AB - OBJECTIVE: In acute respiratory failure, increased cardiac output (Qt) increases shunt (Qs/Qt). We have tested if this is caused by: 1) a redistribution of blood flow towards edematous regions, or 2) a decrease of regional ventilation in the edematous region. DESIGN: Oleic acid edema was induced in the left lower lobe (LLL) of 11 pigs. Qt was varied with bleeding and infusion of blood and dextran. Blood flow to the LLL was measured at low and high Qt with electromagnetic low probes in 6 animals and with a gamma camera in 5. In the gamma camera pigs regional ventilation was also measured. MEASUREMENTS AND RESULTS: Qt was increased by 45% (electromagnetic flow probes) and 73% (gamma camera). Qs/Qt increased from 24.9-31.3% (p < 0.05) and from 17.6-28.8% (p < 0.001) respectively. No change in fractional perfusion of LLL could be seen, neither with flow probes nor with gamma camera. A decrease in ventilation of LLL, 2.6%, was observed when Qt was increased (p < 0.05). CONCLUSION: Theoretically a small decrease in ventilation can explain the increase in shunt, if regions with low ventilation/perfusion (VA/Q) ratio are transformed to shunt. This is, however, unlikely since earlier studies have shown that blood flow is distributed either to regions with normal VA/Q ratio or to shunt regions. We conclude that the cardiac output dependent shunt is not caused by redistribution of blood flow between lobes or by decreased ventilation in the edematous region. We cannot exclude that blood flow is redistributed within the edematous lobe. PMID- 8366226 TI - Selective digestive decontamination by erythromycin-base in a polyvalent intensive care unit. AB - OBJECTIVE: To study the effect of selective digestive tract decontamination by erythromycin-base on the incidence of carriage and infection with MR Enterobacteriaceae producing an extended spectrum beta-lactamase (ESB). DESIGN: After a 10-week prospective survey to ascertain the baseline incidence in two bays (1 and 3) of the same ICU, bay 1 was compared with bay 3 during a further survey of 6 months. The patients in bay 1 received erythromycin-base. SETTING: Two non-contiguous bays, 1 and 3, of 4 beds, in the same polyvalent ICU of a university hospital. PATIENT: Consecutive patients with unit stay longer than 2 days; 34 patients were included during the control period, 43 in bay 1 (decontamination) and 46 in bay 3 (control) during the trial period. INTERVENTION: Erythromycin-base, 1 g t.i.d. in powder form administered by gastric tube to patients in bay 1 from admission to discharge. MEASUREMENTS AND RESULTS: Digestive tract carriage was monitored by cultures of gastric and rectal swab specimens, sampled twice a week. Enterobacteriaceae were isolated on Drigalski agar with incorporated ceftazidime (4 mg/l). In bay 1 there was a decrease in ESB producing Enterobacteriaceae (23% vs 10%, p = 0.0004) from rectal swab, especially in K. pneumoniae (15% vs 2%, p = 10(-5)), during the decontamination period in comparison to the control period. During the trial period the only differences observed between bays 1 and 3 were in the gastric samples: K. pneumoniae were less often isolated in bay 1 than in bay 3 (0% vs 3%, p = 0.03). Intestinal carriage with multiresistant Enterobacteriaceae occurred in 28% patients in bay 1 and 30% patients in bay 3 during the trial period (p = 0.79). Erythromycin-base did not delay the carriage by patients in bay 1 (log rank test p = 0.42). CONCLUSION: Erythromycin-base was not effective in preventing digestive tract carriage due to Enterobacteriaceae resistant to third generation cephalosporin by production of chromosomal cephalosporinase. The decrease in isolates containing K. pneumoniae in bay 1 cannot be definitively attributed to erythromycin-base, since the number of this species in bay 3 was low. PMID- 8366228 TI - Inspiratory pressure/maximal inspiratory pressure ratio: a predictive index of weaning outcome. AB - OBJECTIVE: To compare the accuracy of PI/PImax ratio and other commonly used indices in predicting weaning outcome. DESIGN: A prospective study. SETTING: Intensive care unit. PATIENTS: 31 stable intubated patients ready to undergo weaning trial. METHODS: A simple method was developed to measure the PI and PImax in intubated patients. The accuracy of PI/PImax ratio and other commonly used indices in predicting outcome were compared. All indices were measured prior to weaning trial using standardized methods. MEASUREMENTS AND RESULTS: Minute ventilation of the successful patients (13.00 +/- 0.67 (SE) l/min) was not significantly different from the failure patients (10.64 +/- 1.26 l/min, p = 0.10). The PI and PImax for the successful patients (11.48 +/- 1.25 cmH2O and 47.77 +/- 4.48 cmH2O, respectively) and the unsuccessful patients (14.32 +/- 2.31 cmH2O and 40.16 +/- 4.55 cmH2O, respectively) were also not significantly different (p = 0.28 and 0.24, respectively). The PI/PImax ratio was lower for the weaning successes (0.26 +/- 0.03) than for the weaning failures (0.36 +/- 0.04, p < 0.05). The threshold value of 0.3 for PI/PImax provided the best separation between weaning success and failure patients. The combined usage of rapid shallow breathing index and PI/PImax ratio provided the highest accuracy with sensitivity of 0.81 and specificity of 0.93. CONCLUSION: The PI/PImax ratio provided a good separation between the patients who were successfully weaned and those who failed. It provides additional discriminative power to f/VT. PMID- 8366227 TI - Effects of extrinsic positive end-expiratory pressure on mechanically ventilated patients with chronic obstructive pulmonary disease and dynamic hyperinflation. AB - OBJECTIVE: To examine the circulatory and respiratory effects of extrinsic positive end-expiratory pressure (PEEPe) in patients with chronic obstructive pulmonary disease (COPD) and dynamic hyperinflation during controlled mechanical ventilation. DESIGN: Different levels of PEEPe were applied randomly in mechanically ventilated patients with COPD and dynamic hyperinflation. SETTING: Respiratory Intensive Care Unit of a University Hospital. PATIENTS: 9 patients with acute respiratory failure and dynamic hyperinflation due to acute exacerbation of COPD. INTERVENTIONS: PEEPe 35%, 58% and 86% of intrinsic PEEP (PEEPi) were applied. MEASUREMENTS AND RESULTS: Using flow-directed pulmonary artery catheters hemodynamic measurements were obtained, while simultaneously lung volumes, airflows and airway pressures were recorded. In order to estimate alveolar pressures (Palv), rapid airway occlusions during passive expiration were also performed. At no level of PEEPe were significant changes in cardiac output, gas exchange variables, dead space, airways inflation resistances and respiratory system static end-inspiratory compliance observed. At high level of PEEPe central venous, mean pulmonary arterial and pulmonary capillary wedge pressures were increased significantly. All but one patient were flow-limited during passive expiration. PEEPe 86% of PEEPi caused a significant increase in end-expiratory lung volume and total PEEP. Iso-volume pressure-flow curves showed volume dependence expiratory flow limitation in 2 patients, while in 8 patients volume dependence of critical driving pressure (Palv-mouth pressure) that decreased flows was also observed. CONCLUSIONS: The effects of PEEPe on iso-volume flow and hence on lung mechanics and hemodynamics, depend on many factors, such as airways resistances, lung volumes and airway characteristics, making the patient response to PEEPe unpredictable. PMID- 8366229 TI - Computerized blood gas interpretation as tool for classroom and ICU. AB - OBJECTIVE: To describe structure and function of a PC based blood gas interpretation program (ABG-consultant) developed for nurses and physicians, and to test educational impact and user acceptance. DESIGN: Prospective, blinded study SETTING: Interdisciplinary ICU of a county hospital in Switzerland PARTICIPANTS: Nurses specialized in intensive care INTERVENTIONS: Exposure to the ABG-consultant program MEASUREMENT AND RESULTS: A first group of nurses was subjected to a written examination, then the ABG-consultant was made available for them for 2 months, and finally the same examination was taken again. Additionally, they completed a questionnaire related to the performance of the ABG-consultant. A second group of nurses took the same sequence of examinations but had no access to the ABG-consultant. The score of the examinations increased by 4.8 points in the first group (p < 0.0001) and by 1.3 points (p < 0.16) in the second group. More than 400 consultations were conducted over a period of 2 months and the users themselves stated that the system was of help and easy to use. CONCLUSION: The results have shown that exposure to the ABG-consultant has increased the blood gas knowledge of the ICU nurses. It therefore appears desirable and worthwhile to address other areas of clinical medicine by a similar teaching-consulting approach. PMID- 8366231 TI - Grading asthma severity: using the APS component of the Apache II system. AB - OBJECTIVE: Measurement of severity is fundamental to the description and comparison of case series, treatment regimens and disease outcomes. This study examines the Acute Physiology Score (APS) as a severity measure of an acute "life threatening" asthma attack. DESIGN: The APS in the emergency department (ED) and ICU, demographic, treatment and outcome variables were prospectively studied. Relationships between severity, treatment and progress were investigated. In addition, patients were stratified according to ED APS and differences between the participating hospitals were examined. SETTING: Emergency Departments and Intensive Care Units of two New Zealand hospitals. PATIENTS: 64 admissions to the ICUs following an acute episode of asthma. INTERVENTIONS: Standard management of acute asthma as practised at the two participating hospitals. MEASUREMENTS AND RESULTS: Both the treatment delivered (intravenous salbutamol, sodium bicarbonate and IPPV) and the rate of improvement as defined by change in APS between the ED and the ICU were found to be strongly related to ED APS. Similarly, the length of stay in the ICU correlated with the ICU APS. Stratification on the basis of ED APS allowed small but significant differences in patient physiologic derangement, dose of salbutamol, use of IPPV and incidence of complications to be detected between patients at the two hospitals. CONCLUSION: This prospective study involving two hospitals validates the APS as a method for measuring the severity of an acute asthma attack. It demonstrates how correction for severity can be used to compare treatment and outcome variables in different case series. PMID- 8366232 TI - Intrathecal injection of high-dose meglumine amidotrizoate with complete recovery. AB - Rarely we are faced with accidental spinal injection of potentially toxic substances. We present 2 cases in which amidetrizoate, water-soluble ionic contrast medium, was accidentally injected intrathecally. Our treatment consisted of vigorous hydration and barbiturate coma. This report suggests that for water soluble ionic contrast media increasing cerebrospinal fluid circulation by vigorous hydration may be as effective as spinal lavage in diminishing toxicity. PMID- 8366233 TI - Poor results with mechanical ventilation in AIDS patients with Pneumocysis carinii pneumonia (PCP) PMID- 8366230 TI - Studies on drug monitoring in thrice and once daily treatment with aminoglycosides. AB - OBJECTIVES: To investigate at what time the peak level should be determined under conventional thrice daily (t.i.d.) administration of the aminoglycoside netilmicin and to study its serum concentrations under once daily (od) treatment to define the required daily dose and to gain information about convenient drug monitoring. DESIGN: The design of the study was a consecutive sample trial. SETTING: The study took place in a university hospital. PATIENTS: 41 intubated patients of a surgical ICU who received netilmicin as a short-term infusion over 30 min for life-threatening infections were included in the study. INTERVENTIONS: In 21 patients netilmicin was administered t.i.d. The virtual peak levels which had been determined by pharmacokinetic dosage calculation were compared with the serum concentrations obtained directly after the administration as well as after 15, 30, 60 and 180 min. In 20 patients the netilmicin serum concentrations during od treatment were determined directly before and immediately after the application as well as 0.5, 1, 3, 7 and 12 h later. To achieve a virtual peak level of 25 mg/l and a trough level of 0.5 mg/l individual adjustment of the dosage based on pharmacokinetic calculations was performed. MEASUREMENTS AND RESULTS: In t.i.d. treatment the serum concentration measured after 30 min was closest to the virtual peak level; therefore, this is the best time to determine the peak level. In od treatment the required daily dose was 7.86 mg/kg body weight (median) in patients with normal renal function. During od dosing the trough level was extremely important in drug monitoring, whereas determination of the high peak level was of doubtful value. CONCLUSIONS: The peak level should be determined during t.i.d. administration at 30 min. In od treatment the initial daily dose should be 7 mg/kg body weight; in drug monitoring the trough level is very important. PMID- 8366234 TI - Multiorgan failure (MOF) and intestinal ischemia after cocaine intoxication. PMID- 8366235 TI - Foreign body aspiration mimicking asthma. PMID- 8366236 TI - Cardiac tamponade and hypothyroidism. PMID- 8366237 TI - Acoustical Society of America, 126th Meeting. Denver, Colorado, 4-8 October 1993. Abstracts. PMID- 8366239 TI - Nursing research challenges within health care reform. PMID- 8366238 TI - Notes on nursing today. PMID- 8366240 TI - Identifying the hole in holism. PMID- 8366241 TI - Public policy and creativity in nursing. PMID- 8366242 TI - Faculty improve clinical operations. PMID- 8366243 TI - Educating for the future: a national survey of nursing deans about need and demand for nurse researchers. AB - If nursing doctoral programs are to meet the profession's need for research, they must produce scholars with the specific research foci and skills capable of meeting the profession's unique research demands. A national survey of deans and directors of schools of nursing was conducted to determine their opinions about the differing research foci that graduates of nursing doctoral programs should possess. A mail survey instrument was returned by 434 deans and directors of baccalaureate and higher degree programs who were queried about current and future need, contribution, and funding capability of researchers prepared with five different foci: psychosocial processes, biophysical processes, health care delivery systems and administration, education, and methodology and instrumentation. Deans recommended diverse research foci for both current and future researchers and indicated optimism about future funding for research. Although deans rated current and future professional contributions of researchers in the psychosocial domain most highly, they indicated that they believed current and future funding potential was greatest for biophysical researchers. These deans predicted that all types of nursing research endeavors will become increasingly important to the profession and the development of its theory base. PMID- 8366244 TI - Using large data bases in nursing and health policy research. AB - Concern about the quality, cost, and outcomes of health care has become a driving force in health policy research. The growing accessibility of large clinical and administrative health care data bases has led to an interest in using such data in health policy research. Clinical data bases are created by providers of care and contain data about episodes and outcomes of care, usually organized as patient records. Administrative data bases contain data about indirect care processes such as insurance claims processing, vital event recording, and quality assurance. Clinical and administrative data bases may contain millions of records, consist of data from multiple sites, and often have missing data issues that must be considered by researchers. These and other characteristics of large data bases require special data manipulation and analytic techniques. Large data bases have been used in epidemiological studies, risk assessment, and technology assessment and to study variations in caregiver practice patterns. Because the use of large data bases by nurse researchers has been constrained by the lack of nursing-relevant data in them, there is a need to reach consensus on useful and feasible nursing data elements and to include those data in ongoing data collection efforts by government agencies and private organizations. PMID- 8366245 TI - Developing a nursing doctorate for the 21st century. AB - Nursing in the next century will reflect changes in the health care system, and although the profession has made great strides in preparing nurse researchers, the current system has a serious gap that must be addressed; that of preparing clinical leaders. The article describes the need for a practice-focused doctoral curriculum that will produce a new type of senior clinician or expert practitioner to fill this gap. The envisioned graduates will be skilled in clinical decision making and information processing and will effect changes at both the micro- and macro-levels of the system. There is a clear future need to expand the number of primary care providers. The faculty required for their education must be doctorally prepared nurses who are themselves clinically proficient. The research and practice doctorates should be differentiated by faculty, the program of studies, resources, and placement/expectation of graduates. The article includes a model curriculum plan. PMID- 8366246 TI - Access to graduate education for registered nurses with nonnursing baccalaureate degrees. AB - This article reports a study to evaluate an option for alternate access to graduate nursing education for 85 registered nurses with nonnursing baccalaureate degrees. Using the National League for Nursing Comprehensive Achievement Test (NLN-CAT) to assess knowledge together with successful completion of a special course designed by the faculty, these applicants were admitted to an accredited graduate program in the Lienhard School of Nursing (LSN), Pace University, Pleasantville, NY. The study describes 6 full years of experience using this option. The theoretical rationale; a content analysis for the congruency of content among the NLN-CAT; the terminal objectives of the LSN baccalaureate program; the course outlines and objectives of required upper division baccalaureate nursing courses; and the content of the faculty-designed course, Matrices of Nursing Practice (NUR 589) are presented. Evaluation of NUR 589 for addressing the educational gaps of these students was based on the content analysis described together with the content analysis of the 23 NLN-CAT items incorrectly answered by 50 per cent (N = 12) of successful test takers defined as those who scored at the 70th percentile and higher. Of the 85 successful candidates, 22 did not enter the program, 20 entered and did not complete the program, and 43 were graduated, 6 with distinction. Their grade point averages (GPAs) ranged from 3.37 to 4.00. Results support this method of selection of qualified candidates for graduate education. PMID- 8366247 TI - Baccalaureate educator use of environment-based strategies to teach diagnostic patterns. AB - Baccalaureate nurse educators reported that their use of 10 environment-based strategies in the classroom or clinical setting may foster recognition of diagnostic patterns likely to be encountered in clinical practice. Environment based strategies are verbal or print materials that draw attention to a particular aspect of what is being taught and that draw attention to important information. A national sample of 255 full-time baccalaureate educators (56 per cent return rate) from 28 randomly selected programs completed a questionnaire. The reliability estimate related to the 10 items was 0.70. Most respondents reported use of all 10 environment-based strategies with a minimum reported use of 60 per cent for each strategy on at least a "sometimes" basis. The most frequently reported use of a strategy on a "greater than sometimes" basis was the transparency (75 per cent). Color and print differences were the most infrequently used at 40 per cent and 37 per cent, respectively. The results of this study show that faculty, either consciously or unconsciously, use the environment-based strategies to facilitate student selection of key diagnostic indicators. Increasing educators' awareness of such benefits to students may stimulate further research in this area. Methods to help students decipher significant health status indicators from associated ones are clearly needed so that timely intervention can be used to prevent harm to patients. PMID- 8366248 TI - Group climate: a significant retention factor for pediatric nurse managers. AB - Given today's technical and demanding patient care system within the hospital organization, there is a need for head nurses as nurse managers to be ever more attuned to the climate of their staff. In a study of 34 nurse managers in seven pediatric hospital organizations across a midwestern portion of the United States, an analysis of Fiedler's Leader Match Scales showed the significance of group climate on retention. PMID- 8366249 TI - Nurse empowerment through context, structure, and process. AB - Empowerment is most often conceptualized and measured from an individual perspective. Yet, in the nursing practice environment it requires a more comprehensive perspective. In this article the author requires a more comprehensive perspective. In this article the author proposes that nurse empowerment most likely occurs when there is a congruent linkage among a nursing vision, structural components that involve nurse participation, and the use of a process of inquiry. An empowerment quotient for nursing could be measured on a continuum for each of these three components. PMID- 8366250 TI - Spontaneous activity, conduction velocity and segmental origin of different classes of thoracic preganglionic neurons projecting into the cat cervical sympathetic trunk. AB - Previously, in the anesthetized cat, thoracic preganglionic neurons projecting to the superior cervical ganglion were divided into four classes (groups I-IV) by way of their reflex pattern. Neurons of each class are probably involved in a distinct function, such as regulation of peripheral vascular resistance, regulation of blood flow through skin, regulation of pupil diameter, etc. Here it was tested whether the functionally different classes of thoracic preganglionic neurons also differ in the distribution of their segmental origin, their spontaneous activity and the conduction velocity of their axons. The segmental distribution of preganglionic neurons was almost identical to that determined previously with tracer methods. Distinct classes of neurons had different, although overlapping segmental distributions. Most group III neurons were located in segments T1 and T2, whereas group I, II and IV neurons showed a broader distribution. The subpopulations of preganglionic neurons did not differ in their rate of spontaneous activity. No significant difference was found in segmental distribution between neurons with spontaneous activity and silent neurons. No correlation was found between conduction velocity and spontaneous activity. The proportion of unmyelinated units was greater among group I (16.3%), group II (24.1%) and group IV (22.2%) neurons than among group III neurons (8%). The distributions of conduction velocity were significantly different between group I and group III and between group II and group III neurons. Axons of preganglionic neurons located in segments T1 and T2 conducted faster than axons of neurons located more caudally. The present study shows that distinct subpopulations of preganglionic neurons, as defined by their reflex patterns, differ in their segmental location within the spinal cord and with respect to the conduction velocity of their axons. PMID- 8366251 TI - Tracheal vascular dilatation elicited by vagal nerve stimulation in rats. AB - We investigated the effects of the electrical stimulation of a unilateral cervical vagal nerve on the blood flow in the trachea using laser Doppler flowmetry in urethane anesthetized Wistar King rats. Stimulation for 30 s at 1, 2, 5, 10, 20 or 50 Hz with 10 V intensity caused an increase in tracheal blood flow (TBF) in a frequency-dependent manner; the effects were most dominant with the 10-Hz stimulation among the six frequencies used. The increased responses of TBF with the muscarinic receptor antagonist atropine (1.0 mg/kg, i.v.) were significantly reduced when compared with those without atropine at 5 Hz stimulation (123.3 +/- 11.9% vs. 180.1 +/- 24.5%). This shows the existence of vasodilation due to a cholinergic mechanism. The increased responses of TBF after the ganglion blocking agent hexamethonium (20 mg/kg) i.v. administration were significantly reduced when compared with those without hexamethonium at 1, 2 Hz stimulation (1 Hz: 18.9 +/- 2.7% vs. 35.4 +/- 4.7%, 2 Hz: 40.5 +/- 8.9% vs. 58.8 +/- 6.7%); this shows the existence of vasodilation due to a non-cholinergic parasympathetic efferent mechanism which itself appears to be due to the release of neuropeptides such as VIP and PHI. The increased responses after hexamethonium administration were augmented probably because of the enhanced release of other neuropeptides like SP and CGRP especially at 10 Hz and 20 Hz stimulation. These findings suggest that the mechanism of vasodilation by the activity in the vagal fibers in the trachea of the rat has cholinergic and non-cholinergic efferent components and a non-cholinergic afferent component. In rats, the afferent component may play an important role in controlling tracheal vascular changes. PMID- 8366252 TI - Mechanisms of the secretory response to luminal propionate in rat descending colon in vitro. AB - Short chain fatty acids stimulate Cl secretion in rat descending colon in vitro via an enteric reflex involving mucosa and cholinergic nerves. We used the short circuit current as the measure of Cl secretion caused by Na propionate (NaP) (0.5 mM) in luminal bath fluid and studied the mechanism of the response. The NaP response was decreased 81% by atropine and 76% by lidocaine. It was unaffected by tetrodotoxin, omega-conotoxin or by tachyphylaxis to capsaicin, CGRP, substance P, histamine or PGE2. It was not reduced by inhibitors of 5-HT2 or 5HT3 receptors or by partial tachyphylaxis to 5-HT. However, superficial mucosal injury with hypertonic Na sulfate (2 M) or xylose (4.5 M) reduced the NaP response by 90% and 86%, respectively, and mucosal concanavalin A (1 mg/ml) reduced it by 73%. Neither piroxicam (10 microM) nor nordihydroguaretic acid (10 microM) affected the NaP response. We hypothesize that NaP stimulates the superficial epithelium to release an unidentified agonist that depolarizes predominantly cholinergic nerve terminals and causes colonic secretion. PMID- 8366253 TI - Role of nitric oxide and vasoactive intestinal polypeptide in vagally mediated relaxation of the gastric corpus in the anaesthetized ferret. AB - The roles of VIP and NO in vagally mediated relaxations of the gastric corpus were investigated in the anaesthetized ferret. Intracorpus pressure was recorded manometrically during electrical stimulation of the cervical vagus nerve in three groups of animals: one control group (n = 6), one group treated with an inhibitor of NO synthesis (NG-nitro-L-arginine methyl ester (L-NAME), 1.6 mg/kg); and a third group which had been immunized, prior to the experiment, with a VIP thyroglobulin conjugate (25 nmol equivalent) in Freund's complete adjuvant. In control animals, following treatment with atropine (100 micrograms/kg), vagal stimulation resulted in a frequency dependent fall in intracorpus pressure with the maximum response at 5 Hz of 2.2 +/- 0.3 cm H2O. Two components of the response could be observed: an initial rapid fall over the first 10 s of stimulation followed by a slower decline over the remainder of the stimulation period. In animals treated with L-NAME (n = 6) the initial rapid response was significantly reduced at all frequencies of stimulation (P < 0.05 - P < 0.005, Mann-Whitney U-test) leaving only the slower second component. In immunized animals (n = 6) the initial rapid response to vagal stimulation was not different from control but the slower second component was significantly reduced at 1 Hz (P < 0.005). We conclude that the response to vagal stimulation appears to consist of two components which can be differentiated using L-NAME and autoimmunization to VIP. PMID- 8366255 TI - Clonal attenuation: causes and consequences. PMID- 8366254 TI - Renal vasodilatation in response to acute volume load is attenuated following lesions of parvocellular neurones in the paraventricular nucleus in rats. AB - The effect on the cardiovascular response to volume load, of lesioning the paraventriculo-spinal projection to the lower thoracic cord, has been investigated in urethane-anaesthetised rats. In control animals volume loading with 4% Ficoll 70 in 165 mM NaCl at 0.6 ml/min i.v. up to 1% body weight produced a pressor response and tachycardia accompanied by a vasodilatation in the renal vascular bed. Injections of 2-4 micrograms ibotenic acid in 100-200 microliters solution were made into the paraventricular nucleus to lesion parvocellular neurones. When tested 3 days after the lesioning procedure, the renal vasodilator component of the response to volume load was abolished, although blood pressure and heart rate still rose. When the response to volume load was tested 28 days after the lesion, some degree of functional recovery appeared to have taken place. In these rats there was a weak renal vasodilation although the maximal increase in renal vascular conductance (20 +/- 13%) was still smaller than in the control animals. The efficacy of the lesioning procedure was verified by counting the number of fluorescent labelled neurones in PVN after injection of 1-2 microliters of a 1.25% solution of the retrograde marker 4,6 diamidino-2-phenyl indole (DAPI) bilaterally into the cord at T8-10. 1005 +/- 63 neurones were present in each side of PVN in non-PVN-lesioned rats whilst in lesioned animals only 444 +/- 153 cells were present. These results suggest that the paraventriculo-spinal projection to the lower thoracic cord may play an important role in sympathetically mediated changes in renal blood flow during the early phase of the response to an acute volume load. PMID- 8366256 TI - Aged C57BL/6J mice respond to cold with increased sympathetic nervous activity in interscapular brown adipose tissue. AB - Aged, male C57BL/6J mice produce less heat than adults during cold, which may lead to a reduced ability to maintain core temperature, but the underlying mechanisms of the decreased heat production in aged mice are still unclear. We measured sympathetic nervous activity (SNA) to interscapular brown adipose tissue (IBAT) in aged mice and compared this activity with that of adults. Mice were anesthetized by urethane and isoflurane, and SNA was recorded from one of the fine nerves to IBAT. The animal's body caudal to the pelvic area was covered with a plastic bag containing iced-water to decrease colonic temperature 7 degrees C below control over 20 minutes. SNA to IBAT (IBAT-SNA) increased during cold in both groups, but aged mice had higher IBAT-SNA before and during cold. These findings indicate that neither the ability of aged mice to detect cold nor their ability to generate sympathetic outflow to BAT is deficient. PMID- 8366257 TI - Effects of aging, diet, and sex on plasma glucose, fructosamine, and lipid concentrations in barrier-raised Fischer 344 rats. AB - We studied the relationships of plasma glucose, fructosamine, triglycerides, and cholesterol as a function of age, gender, and diet in barrier-raised Fischer 344 rats aged 5 to 26 months, fed a diet either ad libitum or restricted to 60% of the ad libitum caloric intake. The complex relationships of these plasma levels to age, gender, and diet led to the development of a model with age, diet, and sex as covariates. Overall, fasting plasma glucose concentrations were reduced by approximately 25% in rats on the restricted diet, compared to ad libitum-fed animals. There was a significant age-dependent decline in glucose levels in male animals, whereas in females there was an increase in plasma glucose with aging. Plasma fructosamine levels in calorie-restricted animals, overall, were reduced by 7% compared to levels in animals fed ad libitum. There was a significant positive correlation between plasma glucose and fructosamine levels. Mean plasma triglyceride content was decreased by 50% in calorie-restricted rats compared to ad libitum-fed animals. A significant decrease in triglyceride levels with increasing age was seen in male animals, and an increase with aging in females. There was a significant positive correlation between plasma glucose and triglyceride levels. Plasma cholesterol levels in calorie-restricted animals were reduced by 7% compared to levels in ad libitum-fed animals. An increase of cholesterol concentration with aging was significant in both males and females. Analysis of the data showed that there were significant differences between male and female Fischer 344 rats in the response of plasma glucose and fructosamine to aging and calorie restriction. Changes of plasma triglyceride and cholesterol with aging and dietary calorie restriction were also different in males and females. Studies of the effect of aging on glycemia and blood lipid content should take into account the contributions of animal sex. PMID- 8366258 TI - Beneficial effects of the oral administration of vanadyl sulphate on glucose metabolism in senescent rats. AB - We investigated the effects of the oral administration of vanadyl sulphate (0.5 mg/ml in the drinking water) on glucose homeostasis of 3-month- and 24-month-old rats. Results show that aging is associated with alteration of the oral glucose tolerance test and impairment of the postprandial accumulation of glycogen in skeletal muscles and that the oral administration of vanadyl sulphate rapidly normalizes the inbalance of glucose metabolism in senescent rats. It is suggested that vanadate administration may restore the ability of skeletal muscles of senescent rats to respond to circulating insulin efficiently. PMID- 8366259 TI - Senescent decline in serum dehydroepiandrosterone sulfate concentrations in a population of wild baboons. AB - The physiologic functions of dehydroepiandrosterone sulfate (DS), a precursor of androgens and estrogen and the most abundant steroid in the circulation, are unknown. Nevertheless, numerous studies have shown that low concentrations of DS are correlated with a variety of metabolic and cardiovascular diseases in human beings, and administration of DS to experimental animals is associated with protection from similar diseases. Thus, the marked decline in DS concentrations with age in human beings may be of considerable functional significance. However, because of the difficulties in studying any heterogeneous human population, it has been difficult to assess the extent to which the DS decline with age is confounded by any of a number of factors (e.g., smoking, level of activity, genetics, diet, medication and disease). We studied the effects of age on DS concentrations in a well-characterized population of wild yellow baboons living freely in a national park in East Africa. Study of these animals circumvents many of the confounds just noted. In examining animals ranging in age from juvenile status to old age, we observed a robust decline in DS concentrations with age. The magnitude of the decline is approximately equal in both sexes. In addition, the decline is similar in comparing two baboon groups which have fully natural diets with one group which forages heavily on garbage from people. PMID- 8366260 TI - Acute delirium and functional decline in the hospitalized elderly patient. AB - BACKGROUND: Delirium is often considered a transient cognitive syndrome. Its effect on long-term physical function, however, has not been well defined. METHODS: In a prospective study of 325 hospitalized community and nursing home elderly, we analyzed the effect of in-hospital delirium on subsequent physical function. ADL performance was assessed prior to admission, and at 3 and 6 months after hospital discharge. RESULTS: There was a strong univariate (unadjusted) association between incident delirium and functional decline (p < .02). Delirious subjects lost a mean of almost one ADL, as measured 3 months after hospital discharge. Using multivariate linear regression analysis, with adjusted change in function as the dependent variable, delirium persisted as the sole predictor of loss of function (p = .009) at 3 months after discharge. The functional decline persisted at 6 months after hospital discharge. CONCLUSION: This finding of a nontransient, perhaps permanent consequence of delirium invites reexamination of the definition of delirium from that of an acute, reversible syndrome to one of acute onset with long-term sequelae. PMID- 8366261 TI - Identifying elderly patients for early discharge after hospitalization for hip fracture. AB - BACKGROUND: Some elderly patients can be successfully treated in hospitals with lengths of stay (LOS) shorter than the norms developed by the diagnosis-related groups. This study was designed to test the hypothesis that elderly patients with short LOS after hip fracture have characteristics that can be identified shortly after hospital admission. METHODS: A retrospective chart review was performed of 216 patients over age 55 discharged alive from a university hospital after hip fracture. Demographic, medical, and functional data available within 48 hours of admission were used to develop an algorithm to identify patients eligible for early discharge. A prospective study of an additional 33 patients was undertaken to test this algorithm and to examine the predictive value of additional functional and psychosocial information not routinely recorded in the chart. RESULTS: Retrospective chart review identified 4 predictors of short LOS in multivariate analysis: age less than 75, admission from a nursing home, normality of admission laboratory results, and "no surgery or surgery by day three." These variables explain 25% of the total variation of LOS. In our prospective study the variable "day of surgery" had the greatest variance explanation (30.5%) in multivariate analysis. A model including day of surgery and the presence of dementia explained 42.5% of the variance of LOS. CONCLUSION: Short LOS can be predicted within 48 hours of admission utilizing data that measure severity of illness, functional status, and available support. The development of algorithms to identify patients eligible for early discharge would be beneficial to care managers. PMID- 8366262 TI - Functional performance measures: are they superior to self-assessments? AB - BACKGROUND: It has been suggested that performance measures of functional status have several advantages over self-report measures for both clinical and research purposes, including: greater patient acceptability, interpretability, reproducibility, sensitivity to change, and the focus on actual ability rather than presumed capability. This article challenges this assumed superiority of "objective," "behavioral" measures by directly comparing self-assessments and blindly rated performance assessments on a specific item by task basis, using an identical rating format. METHODS: A set of 14 performance tasks, consisting of a range of functional abilities (including simulations of cooking and sweeping), was administered to 99 community-dwelling older adults (aged 60-92) who had previously completed a 50-item instrumental activities of daily living (IADL) questionnaire. A subsample was retested 2 weeks later, and reassessed at 1 year. RESULTS: Of 182 subjects willing and able to complete the IADL questionnaire, only 99 attempted at least one of the performance tasks. Tasks that took longer to complete were not necessarily associated with a greater number of errors, nor did accuracy ratings correspond well with difficulty ratings. Good correspondence (greater than 80% agreement) between observed and perceived difficulty was found for only one-third of the item/task matchings. Generally, the rater tended to underestimate difficulty relative to subjective assessments. CONCLUSIONS: Relative to questionnaires, performance measures were not found to be psychometrically superior, more acceptable to respondents, easier to administer, or easier to interpret. Neither type of measure by itself distinguishes between motivation and capability, reflects adaptations made in everyday living, or accounts for personal preferences or reasons for difficulty. PMID- 8366263 TI - Cortisol production rate and the urinary excretion of 17-hydroxycorticosteroids, free cortisol, and 6 beta-hydroxycortisol in healthy elderly men and women. AB - BACKGROUND: Although many workers have tested adrenal function in the elderly, few have studied the effect of aging on cortisol production rate or urinary free cortisol or 6 beta-hydroxycortisol excretion, and none have published comparisons of these variables between old people of defined health status and young people. METHODS: We have measured cortisol production rate and the urinary excretion of free cortisol, 6 beta-hydroxycortisol, 17-hydroxycorticosteroids (Porter-Silber chromogens) and creatinine in elderly men and women screened by the SENIEUR protocol and in young men; 17-hydroxycorticosteroid and 6 beta-hydroxycortisol excretion were also measured in young women. The period of measurement was 24 h or, usually, 48 h. RESULTS: Only 6 beta-hydroxycortisol excretion was affected by aging; it was lower in the elderly men and women than in their younger counterparts. Urinary free cortisol excretion was lower in the elderly women than in the elderly men. There were no significant differences between groups in cortisol production rate or 17-hydroxycorticosteroid excretion. Excretion and (over the first 24 h) clearance of creatinine were lower in the old women than in the old men. The cortisol-related variables tended to be positively correlated with each other and with the relevant creatinine-related variables in the elderly subjects; over the first but not the second 24 h, most of the correlations were significant in the men and women combined. CONCLUSIONS: With the exception of 6 beta-hydroxycortisol, the data agree with measurements of plasma cortisol and the results of adrenal function tests in showing little change in hypothalamic pituitary-adrenal function with aging in healthy people. PMID- 8366264 TI - Cross-sectional and longitudinal analyses of stimulated parotid salivary constituents in healthy, different-aged subjects. AB - BACKGROUND: Salivary gland dysfunction has traditionally been associated with old age, and complaints of xerostomia are common in an elderly population. Measurement of certain salivary constituents can provide information about the functional ability of discrete areas of the salivary gland. To our knowledge, this is the first longitudinal study to examine levels of salivary constituents in stimulated parotid saliva in a population of different-aged persons. METHODS: The levels of five salivary constituents (total protein, lactoferrin, proline rich proteins, sodium, and potassium) were measured in stimulated parotid saliva of 47 healthy, unmedicated men and women over a 10.5 year period. RESULTS: There were no significant age-related decreases in the presence of total protein, lactoferrin, proline-rich proteins, sodium, and potassium in this exocrine secretion. CONCLUSIONS: These data confirm and extend previous cross-sectional studies of salivary constituents, indicating that parotid gland function is maintained in healthy aging individuals. PMID- 8366265 TI - Dynamic stability in the elderly: identifying a possible measure. AB - BACKGROUND: The purpose of this research was to assess the ability of trunk acceleration measures to discriminate between the walking patterns of elderly individuals with and without stability problems. METHODS: Twenty volunteers, aged 65 and over, and 19 younger volunteers, all of whom were free of abnormalities or problems that could affect their gait, were recruited for this study. A triaxial accelerometry system was mounted directly over the spine of the upper trunk. Forty seconds of walking data were collected. Using a heel contact switch to define the beginning of the gait cycle, harmonic analyses of each of the 3 acceleration measures were performed on 10 strides. The ratio of summed amplitudes of the even and odd harmonics (index of smoothness) was calculated for each stride and averaged across 10 strides. One-way analyses of variance were used to compare harmonic ratios between groups. Relationships between variables were tested using a correlation analysis. RESULTS: The scores of individuals with stability problems were shown to be significantly different from the younger controls and the older individuals without stability problems for the anterior/posterior and vertical harmonic ratio and peak acceleration measures. CONCLUSION: The results from this research demonstrate that trunk acceleration measures offer the possibility of being able to identify unstable elderly individuals. PMID- 8366267 TI - Aging, inhibition, and verbosity. AB - The hypothesis that off-target verbosity, defined as extended speech that is lacking in focus or coherence, is mediated by an age-related decline in the ability to inhibit task-irrelevant thoughts, was evaluated in a sample of 205 community-dwelling elderly volunteers aged 61-90. Results showed that performance on four tasks that measured the ability to suppress or remove irrelevant information stored in working memory accounted for a significant proportion of the variance in verbosity, whereas performance on other cognitive measures was unrelated to it. Shared effects between the measures of the ability to inhibit task-irrelevant information and age suggested that age declines in this particular ability may underlie previously observed age-related increases in verbosity. In contrast, the contribution of psychosocial factors to explained variance in verbosity scores was relatively independent of that of inhibition related measures and age. The results were discussed as suggesting a possible frontal lobe involvement in off-target speech. PMID- 8366266 TI - Claudication pain and hemodynamic responses to exercise in younger and older peripheral arterial disease patients. AB - BACKGROUND: Claudication patients who are candidates for exercise can frequently walk to maximal pain without experiencing exaggerated blood pressure and heart rate, as well as other clinical symptoms. However, these concomitant problems are more likely to become apparent as patients age. Consequently, this study compared the claudication and hemodynamic responses to exercise in younger and older peripheral arterial disease patients. METHODS: Forty younger (mean age 60.4 yr, range 55-62) and 51 older (mean age 75.5 yr, range 73-81) patients with stable claudication symptoms performed a progressive treadmill walking test to maximal leg pain. The times to onset and to maximal claudication pain, peripheral hemodynamic measurements (oximetry, ankle systolic pressure, and ankle-to brachial systolic pressure index), and central hemodynamic measurements (heart rate and brachial blood pressures) were obtained. RESULTS: Onset and maximal claudication pain occurred 71 sec and 126 sec sooner (p < .05) in the older group, respectively. Greater reductions (p < .05) in foot transcutaneous oxygen tension, ankle systolic pressure, and ankle-to-brachial systolic pressure index were obtained during and following exercise in the older group. Furthermore, smaller increases (p < .05) in heart rate, brachial blood pressures, mean arterial pressure, and rate-pressure product were noted during exercise in the older group. CONCLUSIONS: Greater impairment in the peripheral hemodynamic measurements occurs without exaggerated heart rate and blood pressure responses in older claudication patients who walk to maximal leg pain compared with younger patients. PMID- 8366268 TI - Long-term maintenance of gains from memory training in older adults: two 3 1/2 year follow-up studies. AB - This study investigated long-term effects from memory training in healthy older adults, using samples from two previous studies showing maintenance of gains 6 months after training. In both studies, a multifactorial memory training program (encoding operations, attentional functions, and relaxation) was compared with other training programs. The results from both studies showed that all groups performed at the same level in the 3 1/2-year follow-up as in the 6-month follow up. Most important, the groups receiving training in encoding operations performed at higher levels at the 3 1/2-year assessment compared with pretest. These data indicate that memory training may result in long-term effects for older adults in tasks that are congruent with the training activity. PMID- 8366269 TI - Young and old adults' ability to use different standards to evaluate understanding. AB - In Experiment 1 we examined young (mean age = 22.88 years) and old (mean age = 70.79 years) adults' ability to evaluate their understanding of texts. We examined ability to detect nonsense words (a lexical standard), violations of prior knowledge (an external consistency standard), and inconsistent sentences (an internal consistency standard) that were nonadjacent in texts. Adults with more education detected more problems than less educated adults, and older adults were less able than young to use an internal consistency standard. No age differences were found for lexical and external consistency standards. In Experiment 2, older adults' (mean age = 71.02 years) ability to use an internal consistency standard of evaluation was affected by the amount of material intervening between inconsistent sentences, with hindered performance for nonadjacent inconsistencies. This was not true for younger adults (mean age = 22.59 years). Results are discussed in terms of older adults' possible retrieval difficulty and failure to regulate comprehension. PMID- 8366270 TI - Influence of task-specific processing speed on age differences in memory. AB - Two studies were conducted to investigate the aspect(s) of processing involved in the hypothesized speed mediation of adult age differences in memory. Both studies involved a serial memory task in which information was to be recalled either in the original order of presentation, or in a reordered sequence. Results from both studies indicated that task-specific processing durations were slower among older adults than among young adults, but that the attenuation of the age-related variance in memory was nearly as great after statistical control of a task independent speed measure as after control of task-specific speed measures. These findings are consistent with the hypothesis that a substantial proportion of the adult age-related differences in memory is associated with a decrease with increased age in the speed of executing many cognitive processes, and not simply the speed of one or two specific processes. PMID- 8366271 TI - Construction and validation of the Reminiscence Functions Scale. AB - This research introduces the Reminiscence Functions Scale (RFS), a 43-item questionnaire that can be used to assess reminiscence functions over the lifecourse. Adults (710) ranging in age from 17 to 91 (mean age = 45.76 years) completed a 54-item Reminiscence Functions Scale-prototype measure, the results of which were submitted to a principal components analysis. Results indicated the viability of a 43-item, 7-factor solution with good reliability. Factors were labeled: Boredom Reduction, Death Preparation, Identity/Problem-Solving, Conversation, Intimacy Maintenance, Bitterness Revival, and Teach/Inform. A separate validity study demonstrated the predictive validity of the RFS. Directions for future research are discussed. PMID- 8366272 TI - Race differences in life satisfaction among aged men and women. AB - The purpose of this study was to attempt to explain why race differences emerge in examinations of life satisfaction among older adults retired from the work force. A conceptual model was developed and tested with data provided by 1,156 older Black and White individuals. The findings from this nationwide survey reveal that older Blacks have lower levels of life satisfaction than elderly Whites and that these differences may be attributed to the interplay between past aspirations and plans (as reflected by educational attainment and economic retirement plans) and present financial circumstances (as assessed by current financial strain and economic dependence on family members). PMID- 8366273 TI - Social support and caregiving burden in family caregivers of frail elders. AB - This study assessed the relationships between six different types of social support and five measures of caregiving burden. Two questions were addressed: Are all types of social support equally associated with burden, and do the same types of support correlate with different types of burden? Family caregivers (N = 217) to frail elders composed the sample. Multiple regression analyses demonstrated that all types of social support for caregivers of frail elders are not equal. Engaging in social interaction for fun and recreation appears to be the most important in diminishing the burden of caregiving. These findings are instructive both theoretically and clinically. The theoretical import of greater social participation under a condition of chronic stress is discussed. Further, interventions that focus on caregivers regularly experiencing pleasant activity with friends and other family would seem to go a long way toward managing the burden of caregiving. PMID- 8366274 TI - Driving cessation and changes in mileage driven among elderly individuals. AB - The factors associated with driving cessation, number of miles driven, and changes in mileage were assessed in a community-living elderly population. A driving survey was administered in 1989 to surviving members of the New Haven EPESE cohort. Of 1,331 respondents, 456 had driven and 139 had stopped driving between 1983 and 1989. Independent predictors of driving cessation from a multiple logistic regression model included higher age, lower income, not working, neurologic disease, cataracts, lower physical activity level, and functional disability. These risk factors were combined to assess their ability to predict driving cessation. If no factors were present, no subjects stopped driving; if one or two factors were present, 17 percent stopped; if three or more factors were present, 49 percent stopped. Along with the expected medical factors, physical activity level and social and economic factors contributed to driving cessation. High mileage drivers tended to be younger, active males who still worked. Increasing age and disability were associated with mileage reduction compared to five years earlier. PMID- 8366275 TI - Psychosocial predictors of stroke outcomes in an elderly population. AB - The influence of premorbid psychosocial factors on physical function and institutionalization 6 weeks after hospital discharge was studied in elderly stroke patients. The predictor variables of interest were social networks, availability of social support, pre-stroke depression (CES-D), and religiousness. The data were obtained from a prospective longitudinal study based on 2,812 noninstitutionalized individuals aged 65 years and older living in New Haven, Connecticut. Incident stroke cases from this study were followed for post-stroke outcomes. Results from 87 survivors indicated that larger social networks were associated with fewer limitations in physical function, controlling for relevant health and sociodemographic conditions. Larger networks were also associated with a lower risk of institutionalization (p < .05). None of the other psychosocial factors assessed appeared to be related to these outcomes. PMID- 8366276 TI - Predicting outcomes of nursing home residents: death and discharge home. AB - The purpose of this study was to document prevalence, identify leading indicators, and develop and assess prediction models for nursing home resident outcomes (death, discharge home). New residents (N = 647) in eight nursing homes were evaluated on admission and 3 and 6 months later. Predictor variables tested included 14 health status variables, 5 demographic variables, and 6 other resident and nursing home variables. A cancer diagnosis was the most important risk factor for death at 3 months (OR = 8.0) and 6 months (OR = 10.8). A first nursing home admission was the most important risk factor for discharge to home at 3 months (OR = 9.5) and 6 months (OR = 13.9). Not having a dementia diagnosis was the second most important risk factor for discharge to home at 3 months (OR = 5.8) and 6 months (OR = 4.2). All prediction models demonstrated useful potential for clinical application. PMID- 8366277 TI - 'Shake-up' in drug industry predicted. Interview by Bob Carlson. PMID- 8366278 TI - Managed care and managed competition: preparing for an uncertain future. PMID- 8366279 TI - Hospitals buying physicians' practices. PMID- 8366280 TI - Physicians can help end the violence. PMID- 8366281 TI - Prophylactic knee braces for football: do they work? AB - Knee injuries in athletics are a major problem facing the sports medicine community. There is no compelling evidence to suggest that the likelihood of sustaining a knee injury is increasing; however, more knee injuries are being identified and treated due to improved diagnostic techniques. Successful prevention of knee injuries with prophylactic braces has not paralleled the substantial advances in diagnosis and treatment of these knee problems. This article summarizes the current data available and makes recommendations for subsequent prophylactic knee brace use. PMID- 8366282 TI - Common insurer creates potential conflict of interest. PMID- 8366283 TI - Patent ductus arteriosus in neonates. AB - Patency of the ductus arteriosus is one of the more common problems of the neonate. Although the ductus arteriosus usually closes within the first days of life, persistent patency can complicate the clinical status of a newborn. The ductus arteriosus also may play a role in the pathophysiology of persistent pulmonary hypertension of the newborn and in some forms of congenital heart disease. Diagnosis of patent ductus arteriosus can be suspected clinically but should be verified by echocardiography before treatment. Accurate diagnosis, early intervention and proper treatment are necessary to decrease the immediate risks and minimize the potential for long-term complications. PMID- 8366284 TI - Proton beam therapy using the IU Cyclotron Facility. PMID- 8366285 TI - Optimal circadian timing reduces the myelosuppressive activity of recombinant murine interferon-gamma administered to mice. AB - There is a marked, reproducible circadian variation in the toxicity of a number of antineoplastic drugs. A recent study has employed a murine model to show that recombinant human interferon-alpha A/D (rHuIFN-alpha A/D) exhibited a differential potency in its peripheral white blood cell (WBC)-suppressive and bone marrow-suppressive activities according to the time in the circadian cycle at which it was administered. It was of interest to determine whether another biological response modifier such as IFN-gamma would also exhibit a differential potency during the circadian cycle. A mouse model was used to study peripheral WBC suppression, a toxicity associated with IFN-gamma therapy. Recombinant murine (rMu)IFN-gamma was employed to induce peripheral WBC suppression and was evaluated for its ability to induce peripheral WBC suppression as a function of the time of rMuIFN-gamma administration. Mice were maintained on cycles of 12 h of light and 12 h of darkness. The rMuIFN-gamma was administered at various hours after light onset (HALO). The rMuIFN-gamma-induced peripheral WBC-suppressive effect varied in its intensity in a cyclical manner. Administration of rMuIFN gamma at 4 HALO caused the greatest suppressive effect, whereas administration of rMuIFN-gamma at 14 HALO caused the least suppressive effect. Mice treated at 14 HALO were found to be about 20-fold less sensitive to the peripheral WBC suppressive effects of rMuIFN-gamma than mice treated at 4 HALO. This differential sensitivity to the peripheral WBC-suppressive effects of rMuIFN gamma was examined at six different times in the circadian cycle and was found to be a general effect, occurring throughout the circadian cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366286 TI - Sex hormones and sex hormone-binding globulin in males with chronic viral hepatitis during recombinant interferon-alpha 2b therapy. AB - The effect of long-term treatment with recombinant interferon-alpha 2b (IFN-alpha 2b) on luteinizing hormone (LH), testosterone, free testosterone, and sex hormone binding globulin (SHBG) was evaluated in 7 male patients suffering from chronic viral hepatitis. The drug was given three times a week for 6 months in a single standard dose of 3 x 10(6) units. Hormone evaluations were performed in basal conditions and every 2 months for 12 months. Serum testosterone values decreased after IFN treatment, reaching the lowest levels at the 6th month. However, testosterone values did not fall below the normal range. Serum SHBG concentrations, which were above the normal range in basal conditions, also decreased after IFN. Serum-free testosterone and LH concentrations did not change during IFN therapy. IFN-alpha 2b at the dose and schedule employed was not responsible for any measurable imbalance in male sex hormones. PMID- 8366288 TI - T-cell surface molecule expression and interferon-gamma production in human cord blood. AB - We investigated T-cell surface antigen expression and the production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by human cord and adult blood cells. Cord blood lymphocytes stimulated with Staphylococcus enterotoxin B (SEB) released only minimal titers of IFN-gamma and IL-2 in comparison with adult blood lymphocytes. Systematic analyses of several cell-surface molecules on untreated cord blood and adult blood T cells demonstrated a significant reduction of CD8+ subset numbers in cord blood. Furthermore, cord blood lymphocytes did not express the memory T-cell marker CD45RO. No differences were found in gamma/delta T-cell receptor (TCR), CD5, and CD25 antigen expression between untreated cord blood and adult blood. However, cord blood mononuclear cells showed a decreased CD25 antigen expression in comparison to those of adults following activation with SEB. These observations suggest that the decrease in the proportion of some T-cell subsets and the absence of CD45RO memory T cells may be responsible for the diminished lymphokine production of cord blood lymphocytes. PMID- 8366287 TI - The effect of gonadotropins on the production of human interferon-gamma by mononuclear cells. AB - Gonadotropins--follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (HCG)--and the related agent thyrotropin were shown to enhance yields of interferon-gamma (IFN-gamma) from human peripheral blood mononuclear cells (PBMC) significantly when calcium ionophores (ionomycin or A23187) were used as inducers. The enhancement increased the IFN yields four- to eight-fold. Induction with other inducers, (such as lectins, interleukin-2 (IL 2), and anti CD3, was not associated with enhancement of the IFN yields by gonadotropins. Concentrations of gonadotropins associated with pregnancy (HCG) or menopause (FSH and LH) were able to enhance IFN-gamma yields. Addition of the gonadotropins to the cells after the ionophore gave the greatest degree of enhancement. Perturbation of the calcium messenger system or nonspecific stimulation of adenyl cyclase failed to influence the IFN yield enhancing effect of the gonadotropins. No effect of gonadotropins was observed on IFN bioactivity. PMID- 8366289 TI - Analysis of interferon-alpha 2 sequences in human genomic DNA. AB - We have analyzed the genomic DNA sequence corresponding to the human interferon alpha 2 (IFN-alpha 2) gene locus. In human lymphoblastoid Namalwa cells, we have detected sequences corresponding to IFN-alpha 2b and -2c, while in human KG-1 cells both IFN-alpha 2a and -2b were present. However, in 100 independent IFN alpha 2 clones derived from 20 unrelated Caucasian volunteers, we found only sequences corresponding to IFN-alpha 2b. Statistical analysis of this result suggests that the sequences corresponding to IFN-alpha 2a and -2c are either rare allelic variants of this gene, occurring in only a minority of the Caucasian population, or are restricted to transformed cell lines. PMID- 8366290 TI - Is there a seasonal variation in the interferon-producing capacity of healthy subjects? AB - Induced production of interferon-alpha (IFN-alpha) and IFN-gamma was studied in 101 blood samples from 49 healthy subjects during 1 year. The results indicate a seasonal variation of the IFN-producing capacity, with a decrease in summertime, in Finland. PMID- 8366291 TI - Cyclosporin A inhibits nitric oxide production by L929 cells in response to tumor necrosis factor and interferon-gamma. AB - We recently reported that tumor necrosis factor (TNF) induced the production of nitric oxide (NO) by TNF-sensitive, but not-resistant, tumor cells. Paradoxically, NO thus produced does not appear to be involved in the mechanism of TNF-mediated cytotoxicity as inhibitors of NO production and NO scavengers did not block cytotoxicity. Because the immunosuppressive drug cyclosporin A (CsA) inhibits several types of immune-mediated killing, we were interested in what effect CsA would have on TNF-mediated cytotoxicity as well as NO production. Treatment with CsA had no effect on the sensitivity L929 cells to TNF-mediated cytotoxicity, either in the presence or absence of interferon-gamma (IFN-gamma). In the presence of IFN-gamma alone, L929 cells were slightly less sensitive to the cytotoxic effects of TNF. In contrast to the effect on TNF-mediated cytotoxicity, CsA treatment had a profound effect on the ability of these cells to produce NO in response to TNF and IFN-gamma. Cells treated with CsA produced 75% less NO than did their untreated controls. Inhibition of calmodulin-dependent calcineurin-like phosphatases is one mechanism by which CsA may exert its effects. Therefore, we tested the effect of EGTA, which inhibits calcineurin by chelating calcium, on NO production and found that EGTA treatment resulted in a 15% decrease in the amount of NO produced. In addition, cells treated with the calmodulin antagonist W-13 produced 79% less NO than their untreated controls. Therefore, these results provide further evidence that NO produced by TNF sensitive cells is not involved in the mechanism of TNF-mediated cytotoxicity because reduction of NO production by CsA has no effect on TNF-mediated killing of these same cells. PMID- 8366292 TI - Tissue polypeptide antigen immunostaining in fine needle aspirates from solid breast nodules. AB - The purpose of this study was to determine the role of Tissue Polypeptide Antigen (TPA) immunostaining in the evaluation of aspiration smears from solid breast nodules and to discuss its possible clinical applications. Seventy-one cytologic specimens were studied; 52 were carcinomas, 15 fibroadenomas and 4 fibrocystic dysplasia. TPA was visualized with the peroxidase-antiperoxidase method, using 3 3' diaminobenzidine as chromogen and hematoxylin as counterstaining. The incidence of TPA-positive aspiration smears was 88.5% in the carcinomas and 26.7% in the fibroadenomas. The four cases of fibrocystic dysplasia showed variable behaviour. The intensity of the TPA staining varied from - to and was most frequently high in the carcinomas. The results of this research show a good correlation between a diagnosis of carcinoma and TPA positivity in fine needle aspirates of solid breast nodules. PMID- 8366293 TI - Biochemistry and molecular biology of MCA. AB - The mucin-like carcinoma-associated antigen (MCA) is a mucin with a molecular weight of 350-500 kD. It circulates in the serum and its serum content can be determined with the Cobas Core MCA EIA test. Patients with breast cancer show elevated MCA serum levels. The molecule has a polypeptide backbone consisting of three parts: the C-terminus the N-terminus and the transmembrane sequences. The protein is heavily glucosylated with carbohydrate side chains that contain fucose, galactose and N-acetyl galactosamine. The antibody b-12 recognizes a repetitive epitope on the peptide portion of the MCA molecule. The epithelial mucin, which is coded by a unique gene, was cloned using PCR technology. Peptides corresponding to the N- and C-terminus were expressed in E. coli. Analysis of the purified peptides revealed molecular weights of 12 and 18 kD. PMID- 8366294 TI - Mucin-like carcinoma-associated antigen (MCA) in tissue and serum of patients with breast cancer: clinical applications in prognosis and disease monitoring. AB - Mucin-like Carcinoma-associated Antigen (MCA) has been associated with many breast cancers. The aim of this study was to evaluate MCA in tumor tissue and serum as a potential tumor marker for prognosis and disease monitoring. MCA levels were determined in the tissue of 196 patients with primary breast cancer, 25 with metastatic disease and 25 patients with benign diseases, in pellet and/or cytosol. MCA levels were also determined in the serum of 50 patients with benign diseases, 148 with primary breast cancer (Mo), 150 with metastatic breast cancer (MT), and 200 with no clinical evidence of disease (NED). MCA tissue concentrations in pellet and cytosol were similar: 66.7 + 251 U/mg and 41.1 + 53 U/mg, respectively. No relationship between MCA levels and tumor size or nodal involvement was found. Higher MCA levels were observed in patients with ER+ or PgR+ tumors than in those with ER- or PgR- tumors (p < 0.01). Patients with MCA pellet concentrations lower than 10 U/mg of protein had shorter disease-free intervals (DFI) than those with higher values (p < 0.05). Abnormally high serum levels of MCA were found in 8% of patients with benign diseases, 4% of NED patients, 22% of Mo patients, and in 76% of MT cases. In primary breast cancer MCA values were related to tumor size and nodal involvement. A trend toward a lower DFI in patients with elevated presurgical MCA levels was observed but was of no statistical significance. These differences became statistically significant when patients were subdivided according to nodal status, with shorter DFI in those without nodal invasion (p < 0.05). In metastatic patients, changes in serum MCA were related to the tumor's response to treatment in 82% of cases. The highest MCA values were found in patients with liver or bone metastasis and the lowest values were found in those with locoregional recurrence. In conclusion, although MCA is not a specific tumor marker, it can be useful as a prognostic factor (tissue and serum) and in monitoring metastatic patients. PMID- 8366296 TI - Clinical significance of the new tumor marker MCA in the follow-up of patients with mammary carcinoma. AB - MCA is a mucin-like carcinoma-associated antigen which has been found in all breast cancer independent of histological type and degree of differentiation. A two-step solid-phase EIA was developed and the serum concentration of MCA was measured in 176 breast cancer patients after surgery. Using a cutoff of 11.0 U/ml the test showed a sensitivity of 77% and a specificity of 82% when compared to clinical status. The predictive value of this tumor marker was 72% for a positive diagnosis and 93% for a negative diagnosis. Based on these observations it is recommended that determination of MCA values take place 2 to 3 times in the first postoperative week in all women with surgically treated mammary carcinoma. These MCA values should then serve as reference for further determinations, which should be performed at each check-up. A subsequent increase in the MCA value should be considered as a first sign of metastasis. PMID- 8366295 TI - Mucin-like carcinoma-associated antigen (MCA) in breast cancer: clinical experience at the National Cancer Institute of Milan. AB - Mucin-like Carcinoma-associated Antigen (MCA) is a glycoprotein belonging to the mucin family; it is defined by the monoclonal antibody b-12. Mucins represent an interesting group of tumor markers and are widely utilized in the clinical monitoring of neoplastic patients. These molecules show a certain degree of tissue specificity and MCA is preferentially associated with breast tissue. Several studies have demonstrated that patients with breast cancer usually have high MCA serum levels. In this paper the experience of the National Cancer Institute of Milan with the clinical use of MCA in breast cancer patients is reported. The observed sensitivity of the MCA test was poor in patients with early-stage disease, while it was acceptable in patients with advanced breast cancer. MCA concentrations appeared to be directly related to disease spread. A clear relationship was seen between MCA levels and lymph-nodal status. The highest MCA plasma levels were observed in patients with metastatic disease. In this group of patients the sensitivity of the test on the basis of a cut-off of 11 U/mL was 52%. PMID- 8366297 TI - Rapid, automated enzyme immunoassay for MCA with the Cobas Core Roche immunochemistry analyser. AB - The breast cancer marker Mucin-like Carcinoma-associated Antigen (MCA) was evaluated in a version that has been adapted to a new enzyme immunoanalyser, the Cobas Core. The two-step sandwich assay has a short total assay time of less than 60 minutes. Standard curves are stable for at least 2 weeks. The coefficients of variation for the inter-assay precision ranged between 3.6% and 7.8%, but were mainly below 5%. Single determinations of patient values from different runs correlated also very closely (R = 0.99). The dilution linearity for a set of 14 sera exhibited recovery rates mostly ranging from 90% to 110%. From 165 blood donors investigated, more than 99% had values below the cut-off of 11 U/ml. As demonstrated for pathological sera, the automated and manual versions showed a high degree of accordance (R = 0.98). The investigation presents convincing evidence that the Cobas Core MCA EIA running on a Cobas Core analyser guarantees a high analytical reliability and reproducibility. PMID- 8366298 TI - Immunoscintigraphy in colorectal cancer: surgeon's perspective. AB - External immunoscintigraphy (IS) is a new imaging tool to diagnose, stage and follow-up solid malignancies. Monoclonal antibodies are raised to tumor associated antigens, radiolabeled and when injected in the patient localize to the tumor. Detection is with nuclear medicine gamma camera. In colorectal cancer, immunoscintigraphy can be beneficial to the surgeon. With primary colorectal carcinoma, IS detects synchronous primaries, identifies lymph node metastasis, determines extent of disease and detects occult metastasis. Postoperatively, in high-risk patients (Dukes B2, B3 and C lesions) IS assists in the follow-up for recurrence. Particular advantage with IS is seen in pelvic, mesenteric and retroperitoneal recurrences. Rising serum CEA and negative conventional cross sectional imaging can often be clarified as to site of disease with IS. IS contributes significantly to surgical decision making with alterations in management based on radiolabeled monoclonal antibody scans in 25-32% of primary and recurrent colorectal cancer cases. PMID- 8366299 TI - Usefulness of terminal deoxynucleotidyl transferase as prognosticator in leukemia patients. AB - Peripheral blood samples from 55 previously untreated leukemia patients (33 males, 22 females) were analysed for terminal deoxynucleotidyl transferase (TdT) activity. TdT was significantly higher in patients with acute myelogenous leukemia (AML; P < 0.001), chronic myelogenous leukemia (CML; P < 0.05) and acute lymphoblastic leukemia (ALL; P < 0.001) when compared with controls. One patient with chronic lymphocytic leukemia (CLL) had undetectable TdT. Among leukemic patients, ALL patients had higher concentration of TdT than CML and AML patients. Females had higher TdT activity than males, although the difference between the two groups was not statistically significant. 68% TdT+ and 32% TdT- patients were in blastic crisis. Patients with more than 10% of blasts in the circulation had significantly higher TdT than blast-negative patients (P < 0.001). No difference in survival was observed between TdT+ and TdT- group. From these results, we conclude that the absolute TdT concentration is of little prognostic value in leukemia patients. PMID- 8366300 TI - Squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), and tumour associated trypsin inhibitor (TATI) for monitoring head and neck cancer. AB - Eighty-eight patients with head and neck cancer were prospectively monitored, before and after treatment, by means of simultaneous serum SCC, CEA and TATI measurements. Thirty-two (36.6%) patients had early stages (I, II, III) and 56 (63.4%) advanced (stage IV) or recurrent disease. Pre-treatment serum SCC levels were elevated in 20.4% of patients, CEA in 27.2% and TATI in 4.5%. There was no correlation between the incidence of TATI elevation and tumour burden; this marker did not increase with progressing disease stages. CEA and SCC had low sensitivity in the early stages of head and neck cancer and reached 35.7% (20/56 patients) and 25% (14/56 patients) in stage IV or recurrent disease. Despite the low sensitivity of these tumour markers, there was a correlation between tumour marker levels and the course of the disease. This study indicates that the routine assessment of SCC, CEA and TATI serum levels is of no value. However, it can be used as a potential tool for monitoring the efficacy of individual therapy in both early and advanced stages of head and neck cancer. PMID- 8366301 TI - CEA and CA 15-3 in pleural effusion of advanced breast cancer patients: clinical relevance and diagnostic value. AB - Serum and pleural effusion fluid were tested for CEA concentration in 83 advanced breast cancer patients, in 43 of whom CA 15-3 was also determined. All pleural effusions were clinically malignant. The sensitivity of the CEA test for the presence of pleural metastases was closer to that of the CA 15-3 test in effusion (0.59 and 0.79, respectively) than the sensitivity of CEA compared to CA 15-3 in serum (0.43 vs. 0.79). The use of two markers combined with cytology increased the diagnostic rate from 48% (cytologically positive) to 88% (cytologically positive and/or with one or both markers increased in effusion). A high diagnostic rate in cytologically negative effusions (65%), and in effusions presented as the sole metastatic involvement (100%), points to the clinical value of these two markers. Our results show that markers produced by pleural metastases may be secreted either into the effusion fluid or into serum, or both. This finding, as well as some other observations, are discussed in the present paper. PMID- 8366302 TI - Combined treatments of heat, radiation, or cytokines with flavone acetic acid on the growth of cultured endothelial cells. AB - The antitumour effects of flavone acetic acid (FAA) against a broad spectrum of established experimental tumours has been demonstrated. Damage to the vasculature, which rapidly disrupts blood flow and induces haemorrhagic necrosis, is believed to be a major mechanism contributing to the observed antitumour effects. Despite these established observations, FAA has shown little effect against human tumours. However, other applications of FAA, for examples, for an extended period of treatments or in combination with other antitumour modalities, have not been sufficiently explored. In order to test the direct effects of FAA on vasculature, endothelial cells isolated from human umbilical vein (HUVEC) and bovine pulmonary artery (CPAEC) were used in this study. FAA at the concentrations of 50 to 200 micrograms/ml causes reduction in cell number (from 20 to > 30% of the cells) of HUVEC as measured by MTT assay after 1, 3, and 5 h of treatment at 37 degrees C. FAA did not produce significant effects on similarly treated human squamous cell carcinoma, cell line UM-SCC-2. After 1 h treatment of FAA at 300 micrograms/ml, a large number of HUVECs failed to react with an actin stain, NBD-phallacidin. The growth of HUVECs and CPAEC in the presence of FAA for 1-3 days was progressively reduced. The number of HUVEC treated for 3 days at the concentrations of 100, 200, and 300 micrograms/ml were reduced by 75-86% in comparison with the control culture. The experiments with CPAEC showed similar results. The inhibition of the growth of endothelial cells by FAA was enhanced when it combines with tumour necrosis factor-alpha but not with interleukin-1, interferon-gamma, heat, or radiation. We observed that FAA can initiate both immediate effects and growth inhibition on cultured endothelial cells. These results support the notion that FAA rapidly induces vasculature damage. Furthermore, cytokines such as tumour necrosis factor-alpha can enhance the toxicity of FAA on endothelial cells. PMID- 8366303 TI - Kidney trace metal response to combined cisplatin (CDDP) and hyperthermia. AB - The effects of hyperthermia (HY) on cisplatin (CDDP) nephrotoxicity and kidney metal concentrations were evaluated in female F344 rats. Rats were anaesthetized with a xylazine/ketamine mixture, heated on a water-bed for 1 h to an intraperitoneal temperature of 41.1 +/- 0.2 degrees C, and maintained at hyperthermia for an additional 30 min (HY plateau). CDDP (5 mg/kg body weight) was administered at the start of the heating or at the HY plateau. Neither HY alone nor CDDP (5 mg/kg) at normothermia produced a significant effect on weight loss or nephrotoxicity. CDDP administered at the start of heating produced a moderate 1.5-fold increase in serum urea nitrogen (SUN) and serum creatinine concentrations. CDDP administered at the HY plateau produced a significant six fold increase in SUN and a four-fold increase in creatinine concentration. Weight loss increased two- to three-fold from the combined regimen, but only the rats given CDDP at the HY plateau continued to lose weight through day 7. A loss of kidney copper (50-60%) resulted from the combined regimen, similar to losses observed with higher doses of CDDP at normothermia. HY alone had little effect on concentrations of kidney copper or zinc up to 4 days post-treatment. The results demonstrate that systemic hyperthermia significantly increases CDDP nephrotoxicity in F344 rats and that kidney copper loss from CDDP exposure at hyperthermia is similar to the loss observed from CDDP at normothermia. PMID- 8366304 TI - An immunoassay for heat shock protein 73/72: use of the assay to correlate HSP73/72 levels in mammalian cells with heat response. AB - An enzyme-linked immunosorbent assay (ELISA) for measurement of levels of heat shock proteins 73 and 72 (HSP73/72) in cultured cells and tissues is described. The assay involves detection of HSP73/72 in cell homogenates in 96-well plates using a specific monoclonal antibody. The assay has been used to explore the relationship between the amount of HSP73/72 in a cell and its response to heat shock, both before and after the development of thermotolerance. Six mammalian cell lines with differing responses to heat were characterized with respect to their response to heat treatments at 44 degrees C and concentrations of HSP73/72. Contrary to the widely expressed idea that the amount of HSP73/72 dictates the degree of heat resistance, no positive correlation between levels of HSP73/72 and heat resistance was found for the six lines tested here: if one particular line, a mutant selected for heat resistance, was excluded from the analysis, there was a negative correlation between HSP73/72 levels and heat resistance. A different result was, however, obtained when thermotolerant (transiently resistant) cells were compared to control cells. Here, we found a good correlation between the extent of thermotolerance and the amount of HSP73/72, suggesting that an increase in HSP73/72 level is important for the development of thermotolerance. The validity of the ELISA technique was checked using a second method for quantifying levels of HSP73/72. This involved uniform radiolabeling of cellular proteins, separation on two-dimensional gels and radioscanning to quantify radioactivity in each protein. The second technique is more powerful in that different isoforms of HSP73/72 can be distinguished, but it is more difficult to perform, is more labour intensive and requires an expensive device for gel scanning. The results using the second technique agreed well with those from the immunoassay and indicated that the level of the highly inducible HSP72 correlated best with the extent of thermotolerance. PMID- 8366305 TI - Sensitizing for cis-diamminedichloroplatinum(II) action by hyperthermia in resistant cells. AB - cDDP-resistant Ehrlich ascites tumour (EAT) cells (ER cells) were tested for cellular content of total glutathione, heat sensitivity, cDDP sensitivity and synergistic effects of a combined treatment of heat and chemotherapy. In comparison with the non-resistant EAT cells (EN) the ER cells had an elevated level of glutathione. Treatment with D,L-buthionine-(S,R)-sulphoximine (BSO), resulting in almost complete depletion of cellular glutathione, did not cause drug sensitization. The ER cells were somewhat less heat sensitive compared with the EN cells. Heat chemosensitization was observed for the EN cells as well as for the ER cells. At 43 degrees C (but not at 42 degrees C) the thermal enhancement ratio (TER) for cDDP toxicity was significantly higher in the ER cells. The total number of cells killed by the combined treatment was less in the ER cells than in the EN cells. After analysing existing literature, combined with the current results, it is concluded that although cDDP-resistant cells can often considerably be chemosensitized by hyperthermia, in most cases the difference in cDDP sensitivity cannot be overcome totally. In those situations where cDDP resistant cells are more sensitive to heat and also show a high TER, especially at clinically relevant temperatures, hyperthermia as added modality is indicated for clinical treatment. PMID- 8366307 TI - Experimental evaluation of two simple thermal models using hyperthermia in muscle in vivo. AB - The predictions from two simple field equation models for calculating temperature distributions in tissue, namely, the Pennes' bioheat transfer equation (BHTE) and an effective thermal conductivity equation (ETCE), were compared to in vivo experimental temperature measurements made under hyperthermic conditions generated by scanned focused ultrasound. The models were kept simple (i.e. homogenous isotropic properties, no separate blood vessels included) in order to concentrate attention on the predictive abilities of these field equations using a minimum number of free parameters. Simulated results were fitted to the experimental data (multiple, linear temperature profiles in the thigh muscles of greyhound dogs) by minimizing a performance index using a golden section searth. This search determined a value for the single free parameter in each model (blood perfusion in the BHTE, and effective thermal conductivity in the ETCE) which minimized the square error difference between the experimental and simulated temperatures. The results showed that (a) the simple BHTE model could qualitatively reproduce the major features of the temperature patterns seen experimentally better than the ETCE model could, and (b) the simple BHTE model produced better quantitative fits to the experimental data than did the simple ETCE model. In addition, blood perfusion predictions from the BHTE model compared well to measurements done with coloured microspheres. Finally, the experimental results showed that individual, large blood vessels appeared to have a major influence in producing asymmetries in the experimental data in 21% of the measured temperature profiles. PMID- 8366306 TI - Performance of an adaptive MIMO controller for a multiple-element ultrasound hyperthermia system. AB - A prototype adaptive automatic control algorithm was implemented to regulate temperatures measured at several points in a tumour by adjusting the power applied to several ultrasound transducers. The goal was to control the temperatures under the elements of a mosaic applicator individually without any priori knowledge of which probes are under which elements. The control algorithm was devised for clinical applications where the position of each probe with respect to the heat sources is difficult to determine precisely. Instead, the program 'learns' the relationship between the inputs (power levels) and the outputs (temperatures) automatically. Based on the observed transfer function relating the power at m sources to the temperatures n probes, where n and m are not necessarily the same, a new method was used to implement a feedback controller. This method simplifies the design of the controller for a multiple input/multiple-output (MIMO) system, while taking into account the coupling that may exist between the various elements of the system. As a result of using an adaptive scheme, the regulator continuously tracks changes in the system, such as blood flow variations or patient motion, by modifying its control parameters. The algorithm performance has been tested in simulations as well as experiments in dog thigh and a perfused kidney model. PMID- 8366308 TI - Application of multiple modelling to hyperthermia estimation: reducing the effects of model mismatch. AB - Multiple model estimation is a viable technique for dealing with the spatial perfusion model mismatch associated with hyperthermia dosimetry. Using multiple models, spatial discrimination can be obtained without increasing the number of unknown perfusion zones. Two multiple model estimators based on the extended Kalman filter (EKF) are designed and compared with two EKFs based on single models having greater perfusion zone segmentation. Results given here indicate that multiple modelling is advantageous when the number of thermal sensors is insufficient for convergence of single model estimators having greater perfusion zone segmentation. In situations where sufficient measured outputs exist for greater unknown perfusion parameter estimation, the multiple model estimators and the single model estimators yield equivalent results. PMID- 8366309 TI - Guide for the protection of occupationally-exposed personnel in hyperthermia treatment from the potential hazards to health. PMID- 8366310 TI - A new respiratory rate monitor: development and initial clinical experience. AB - The need for continuous, noninvasive, and reliable respiratory rate monitoring during recovery from general anesthesia has long been recognized. Alternative principles can be grouped into those detecting the respiratory effort, and those detecting the actual result, i.e. the respiratory gas flow. The second category is of greatest interest for patient monitoring. In this paper, we report the development and initial clinical experience with a new acoustic air-flow sensor. By differential, multipoint detection of the air-flow in the mouth and nose region, the sensor can easily discriminate against different kinds of interference, including motion artefacts. The sensor is nonexpensive, rugged, simple to apply and inherently safe. An instrument with continuous display of respiratory rate, and an audiovisual apnea alarm has been designed and built. The complete system has been tested on patients during recovery after general anesthesia. In 16 patients, the respiratory rate displayed by the instrument has been correlated against that visually observed. A good correlation was obtained. Minor discrepancies can be explained from the fact that visual observation corresponds to the respiratory effort, whereas the sensor detects the actual air flow. In 12 patients, 24 hour simultaneous recordings were made of respiratory rate with the new sensor, with simultaneous recording of the oxygen saturation and the heart rate with a pulse oximeter. It was found that the new sensor reliably recorded respiratory depression and apnea. Such events may in some patients be as frequent as one incident per hour. One case of 'Ondine's curse' provided clear evidence that pulse oximetry has a low sensitivity to respiratory disorders. PMID- 8366311 TI - Anesthesia record keeping. PMID- 8366312 TI - A knowledge-based alarm system for monitoring cardiac operated patients- technical construction and evaluation. AB - A knowledge-based alarm system for intensive care monitoring was designed, built, tested on-line, and evaluated. The system is a functional prototype of a highly specific patient monitor providing alarms on hypovolemia, hyperdynamic state, left ventricular failure and hypoventilation. These intelligent alarm functions aim to maintain the quality of patient monitoring even if nurses' attention is temporarily reduced or focused elsewhere. The alarm system has an electronic access to data available in a multichannel patient monitor and the patient data management system of the intensive care unit. Median filtering, trend estimation, and rule-based reasoning are applied when processing the measured variables and estimating the patient's state. PMID- 8366313 TI - Bedside measurement of work of breathing. AB - This paper describes the technique of measuring work of breathing, presented at the 13th International Symposium on Computers in Clinical Medicine and Anaesthesiology, Rotterdam, June 1992. Measuring work of breathing has clinical uses in the Intensive Care Unit. Oxygen consumption does not truly reflect work of breathing. Mechanical work of breathing can be measured by recording continuous pressure and flow and integrating the resultant power. This method is facilitated at the bedside with the use of a PC computer and a spreadsheet program. It is further simplified by software to measure the area under the inspiratory pressure: volume loop. PMID- 8366314 TI - A knowledge based interpretation system for EMG abnormalities. AB - The conventional method of diagnosis in electromyography is complex and time consuming, not only due to the large number of parameters, to be considered for diagnosis, but also because of the usual procedure of evaluating the different parameters of EMG signal by visual scanning of the plotted signal. So there is a clear need to make use of computer aided decision support system. In the present work an attempt has been made in the direction of integration into one automated system, the qualitative knowledge of the physician, with possibly sophisticated signal analysis tools which must replace the visual scanning. A software program (in Turbo-C) on a PC-AT has been developed to evaluate the different parameters of MUAP's (motor unit action potential) in a EMG signal. Then an Expert system (in Turbo-Prolog) has been implemented for diagnostic purposes of different muscular abnormalities by making a knowledge base from the different parameters involved in the decision making procedure of clinical electromyography. A hybrid model of rule and frame based Expert system is implemented. An attempt has been made for making a complete system, i.e., for recording, analysis and decision making for diagnosis. PMID- 8366315 TI - Omar Prakash, MD PhD 1936-1993. PMID- 8366316 TI - Metaphor graphics to support integrated decision making with respiratory data. AB - Support for data integration in the intensive care unit (ICU) often includes efforts to improve the display of data. An electronic version of a flowsheet (table of numbers) with optimal line graphs is by far the most common format in current ICU computer workstation technology, yet there is little evidence that this format provides particularly good support for human integration of data. The present work introduces a new form of graphic representation, one that is far more metaphoric, far more tailored to the intensive care unit than a line graph. This graphic system, called volume rectangles represents mechanical ventilator data in such a way that is easy to keep different types of variables conceptually separated, yet easy to see how they relate in a truly integrated way. Volume rectangles are one example of a general approach to display of data called the metaphor graphic approach, which is being evaluated in this and other contexts. Metaphor graphics are custom tailored visual displays designed to look like the real world situation from which the data is collected but not in a literal sense of 'look like'. Anecdotal observation suggests that such graphics are easy to learn, are remembered over long period, and are good decision support tools when the task is finding patterns in a mass of data. PMID- 8366317 TI - Living with euthanasia: a futuristic scenario. AB - In 1991 and 1992, citizens of Washington State and California voted on whether "aid-in-dying" should be legalized. In both states, the proposition was defeated. In this article, the author, who participated in the Washington State campaign, imagines what might have happened in the fictitious State of Redwood, had such a proposal passed. PMID- 8366318 TI - Learning to do no harm. AB - The legalization of euthanasia creates a certain tension when it is compared with those traditional medical principles that seem to embody respect for the sanctity of life. It also creates a real need for us to explore what we mean by harm in relation to dying patients. When we consider that we must train physicians so that they not only understand ethical issues but also show the virtues in their clinical practice, it becomes important for us to strive to train them in virtue rather than mere knowledge. We can only do this by conveying a real sense of the needs of the patient and an ability to relate to patients as people not problems. Such attitudes take shape in a training programme in which practical situations are explored and discussed and the limits of scientific medical responses to those challenges are exposed. PMID- 8366319 TI - The medicalization of dying. AB - Physician assisted suicide or active euthanasia is analyzed as a medicalization of the needs of persons who are suffering interminably. As with other medicalized responses to personal needs, the availability of active euthanasia will likely divert attention and resources from difficult social and personal aspects of the needs of dying and suffering persons, continuing the pattern of privatization of the costs of caregiving for persons who are candidates for active euthanasia, limiting the ability of caregivers to assist suffering persons to make their continued suffering tolerable, and casting doubt on the voluntariness of the choice of active euthanasia. PMID- 8366320 TI - Altruism and physician assisted death. AB - We assume that a statute permitting physician assisted death has been passed. We note that the rationale for the passage of such a statute would be respect for individual autonomy, the avoidance of suffering and the possibility of death with dignity. We deal with two moral issues that will arise once such a law is passed. First, we argue that the rationale for passing an assistance in dying law in the first place provides a justification for assisting patients to die who are motivated by altruistic reasons as well as patients who are motivated by reasons of self-interest. Second, we argue that the reasons for passing a physician assisted death law in the first place justify extending the law to cover some nonterminal patients as well as terminal patients. PMID- 8366321 TI - Advance directives for voluntary euthanasia: a volatile combination? AB - Defenders of patient autonomy have successfully supported the legal adoption of advance directives. More recently, some defenders of patient autonomy have also supported the legalization of voluntary active euthanasia. This paper explores the wisdom of combining both practices. If euthanasia were to become legal, should it be permitted by advance directives? The paper juxtaposes the most significant doubts about advance directives, with the most significant doubts about euthanasia. It argues that the doubts together raise more concern about the combined practices than about either euthanasia or advance directives separately. Not all cases of voluntary euthanasia by advance directive are equally problematic, however. Advance directives can help in the defense of euthanasia for patients who make the request in advance and reaffirm it under circumstances of severe suffering. PMID- 8366322 TI - Conscience, referral, and physician assisted suicide. AB - Practices such as physician assisted suicide, even if legal, engender a range of moral conflicts to which many are oblivious. A recent proposal for physician assisted suicide provides an example by calling upon physicians opposed to suicide to refer patients to other, more sympathetic, physicians. However, the proposal does not address the moral concerns of those physicians for whom such referral would be morally objectionable. PMID- 8366323 TI - Physician assisted death and hard choices. AB - We argue that after the passage of a physician assisted death law some inequities in the health care system which prevent people from getting the medical care they need will become reasons for choosing assisted death. This raises the issue of whether there is compelling moral reason to change those inequities after the passage of an assisted death law. We argue that the passage of an assisted death law will not create additional moral reasons for eliminating inequities simply because they become motives for someone to opt for assisted death. We also argue that it is not feasible to eliminate these reasons for opting for assisted death by granting a right to health care because of an intractable scarcity of medical resources. PMID- 8366324 TI - Feature-based versus exemplar-based strategies in preschoolers' category learning. AB - Five experiments examined whether preschool children learn categories by formulating a categorization rule based on attention to one or two features, or by memorizing the category assignment for whole exemplars. Using fictitious animals as stimuli, children were taught a two-category discrimination at the basic level and were tested for their category learning using a procedure that required them to categorize from memory, rather than perform perceptual matching. Transfer stimuli manipulated the retention of features encountered in the training instances, and children were instructed to classify only the items about whose category membership they were certain. By measuring the extent of generalization, in addition to categorization accuracy, it was possible to assess whether children were applying a feature-based rule in making their categorization decisions. The studies found little evidence that children were employing rules. Analyses of the individual response patterns identified few children who categorized by attending to a single attribute such as shape, or else who used a two-feature disjunctive rule. In addition, a recognition memory test given after category gaining produced strong evidence that children had encoded the training examples as wholes, rather than focusing on individual features. Despite clear evidence that children had encoded the training examples, however, examplar information was not used successfully in categorization when subjects were trained on only a single instance per category. The implication of these results for theories of early categorization are discussed. PMID- 8366325 TI - Exclusion vs. selection training of auditory-visual conditional relations. AB - This study was conducted to assess the relative effectiveness of exclusion vs. selection (modified trial-and-error) training in establishing auditory-visual conditional relations. The study was conducted with children who had problems learning in school, but were otherwise normally intellectually capable. Single subject methodology was used. Each child was exposed to the exclusion and selection conditions twice each in varied order. The exclusion-training procedure proved significantly more effective not only in teaching new auditory-visual conditional relations but also in generating emergent naming of the visual stimuli. PMID- 8366326 TI - Development of phonological and orthographic skill: a 2-year longitudinal study of dyslexic children. AB - Twenty-one dyslexic children, ages 9-15, were administered a battery of tests on two occasions separated by 2 years to assess the development of word recognition and spelling. The majority of the subjects were receiving intensive small-group instruction and one-on-one tutoring in reading and writing. Correlational and regression analyses supported the assumption that phonological and orthographic processing are distinct but reciprocally related components of word recognition and spelling. However, phonological skill appeared to capture most of the unique variance in word identification for dyslexics and younger normal readers matched on word identification skill. Although the dyslexic children made significant gains over 2 years in overall word identification skill and in aspects of phonological and orthographic processing, they failed to show significant "catch up" in any component skills relative to age- and reading-level-matched normal readers. In addition, dyslexics made little or no progress on a measure of phonemic analysis, on a decoding task requiring processing at the level of the phoneme, and at spelling words with unusual and irregular orthography. The results are consistent with the hypothesis that dyslexic children have primary deficits in phonological processing of speech and print and secondary deficits in orthographic processing. PMID- 8366327 TI - Working memory in learning disability subgroups. AB - The purpose of this study was to investigate (a) the degree to which working memory differences between learning-disabled and nondisabled children reflect a specific or generalized deficit, and (b) whether limitations in the enhancement of learning-disabled student's working memory performance are attributable to process or storage functions. To this end, performances of reading-disabled, math disabled, chronological age (CA)-matched, and achievement-matched children were compared on verbal and visual-spatial working memory measures under initial, gain, and maintenance conditions. The results indicated that: (a) learning disabled subtypes were not differentiated by their performance on verbal and visual-spatial working memory measures; and (b) learning-disabled children's working memory performance was inferior to CA-matched and superior to achievement matched counterparts across initial, gain, and maintenance conditions. The results suggest that learning-disabled children suffer generalized working memory deficits, possibly due to storage constraints in the executive system. PMID- 8366328 TI - The fears of youth in the 1990s: contemporary normative data. AB - This article reports the findings of a normative fear investigation involving a sample of 918 Australian children and adolescents, ranging in age from 7-18 years. The Fear Survey Schedule for Children and Adolescents-II (FSSC-II) was administered to determine self-reported prevalence, intensity, and content of fear. Consistent with past research, girls generally reported significantly higher levels of fearfulness than boys. Age differences also were found; younger children reported a higher intensity and a greater number of fears than older children and adolescents. Qualitative differences in normative fear were found, with younger children reporting more animal fears and older children reporting more fears relating to social evaluation or psychic stress. Significantly, although the specific content of children's and adolescents' normative fears in the 1990s (as compared with the 1960s) has changed (now including fear of AIDS and of nuclear war), the fears found to be most prevalent continue to relate to death and danger. These findings are discussed within the context of the prepotency and preparedness concepts of fear. PMID- 8366329 TI - The structural consistency of moral judgments about AIDS. AB - This study compared the structure (i.e., stage) of moral judgments to dilemmas involving AIDS to the structure of moral judgment on Kohlberg's test to determine whether attitudes and opinions about AIDS affect level of moral judgment. Subjects included 40 men, who responded to (a) two standard dilemmas from Colby and Kohlberg's (1987) test of moral judgment, (b) two of Kohlberg's dilemmas ammended to involve AIDS, (c) a set of AIDS dilemmas derived from incidents reported in the media, (d) a set of questions tapping attitudes toward people with AIDS, and (e) Rubin and Peplau's (1975) just-world scale. Moral judgment was structurally consistent across the three sets of dilemmas, and only weakly related to attitudes towards AIDS and belief in a just world. Moral choices did not covary with moral stage. These results are consistent with Kohlberg's contention that moral judgment is organized in "structures of the whole." PMID- 8366330 TI - Response perseveration, inhibitory control, and central dopaminergic activity in childhood behavior disorders. AB - We screened students (N = 710) in grades four through six at two public elementary schools for behavior problems, using the Revised Behavior Problem Checklist. Five groups of children were identified: conduct disorder (n = 8), attention deficit disorder (n = 9), conduct disorder plus attention deficit disorder with hyperactivity (n = 11), anxiety-withdrawal (n = 12), and normal control (n = 15). A response perseveration task, inhibitory control task, and a noninvasive measure of dopaminergic activity were administered to selected students, and group differences were predicted based on Quay's hypotheses as derived from Gray's theory of brain function. Hypothesized group differences were not found, although analyses revealed dimensional relationships that were consistent with the hypotheses. Results are discussed in terms of Quay's hypotheses and potential modifications to tasks for future research. PMID- 8366331 TI - Sex differences in reaction times, decision times, and movement times in British and Korean children. AB - In this study we compared reaction times broken down into decision times and movement times between 9-year-old British and Korean boys and girls. Boys tended to be faster on movement times, but there was no sex difference in decision times. These results were obtained on three reaction-time tasks of different levels of complexity. PMID- 8366332 TI - Attitudes of preschool children toward their peers with disabilities: a year-long investigation in integrated classrooms. AB - Changes in choices of preferred playmates by 3- and 4-year-old children were observed over the course of a school year. All of the children in this study participated in planned, fully mainstreamed, same-age preschool classes. Sociometric assessments were obtained from all children without disabilities in October, February, and May of the school year; peer nominations of three "best friends" were obtained at the beginning and end of the school year. The 3-year old children showed a general decline in the ratings given to all of their peers over the course of the school year. Four-year-old children showed significant preferences for same-sex peers without disabilities as playmates. The implications of these findings for integrated programs are discussed. PMID- 8366333 TI - Age differences in memory-span errors: speed or inhibitory mechanisms? AB - This study investigated age differences in errors on the digit-span task. Protocols of 119 men and women, aged 18-99 years, were scored for the occurrence of three types of errors derived from the speed-of-processing and inhibition deficit frameworks: omission errors, intrusion errors, and transposition errors. The types of errors made on the digit-span task varied with span size. At larger span sizes, participants were more likely to omit digits or introduce nonstimulus digits than to transpose those in storage. No age differences in intrusion errors were found, however, old-old women (75+ years) were significantly more likely than young (18-25 years) and old (60-70 years) adults of either sex to exhibit transposition errors. Consequently, old-old women were significantly less likely to exhibit omission errors. The results indicate that the digit-span task may involve two parallel processes: digit storage/recall and serial/position storage recall. Age differences in the serial-processing component, rather than in the digit storage/recall component, may be age sensitive. These results are discussed within an inhibition-deficit framework of cognitive aging. PMID- 8366334 TI - Children's coping styles and report of depressive symptoms following a natural disaster. AB - The present study examined the relationship between children's coping styles (Spirito, Stark, & Williams, 1988) and self-reported levels of depressive symptoms (Kovacs, 1983) following a major stressor. 257 third- to fifth-grade children consented to participate in the study, 5 months following a hurricane. The number of coping strategies employed was positively related to depression scores, whereas coping efficacy was negatively related to depression scores. Social withdrawal, self-blaming, and emotional regulation were associated with more severe depressive symptoms. Lower levels of symptomatology were found among children who sought social support and engaged in cognitive restructuring. The overall symptom level in the sample did not exceed that of normative samples. Results are discussed in terms of competing theories of childhood depression. PMID- 8366335 TI - Generalists in SCI medicine: good, bad or indifferent? PMID- 8366336 TI - Is chronic spinal cord injury associated with increased risk of venous thromboembolism? AB - To determine the incidence of symptomatic thromboembolism in patients with chronic spinal cord injury, a retrospective review of patients followed in a Veteran's Affairs Spinal Cord Injury Unit was conducted. Followed for a mean of 13.7 years after injury, 287 patients were reviewed. Forty events were identified, an incidence of 10 percent. Thirty-three (83 percent) occurred in the first 6 months following injury. The remainder occurred at 1, 1.5, 7, 9, 10, 12, and 14 years after injury, an incidence of 0.17 percent per year. The incidence of clinically significant thromboembolism in spinal cord injury decreases dramatically after the first 6 months to a level similar to that in the general population (0.18 percent). Possible explanations for this include: 1) immobilization by itself may not be a risk factor for thromboembolism; 2) physiologic adaptations in the chronic state may protect against thromboembolism; and, 3) thromboembolism occurs, but remains subclinical in most patients. PMID- 8366337 TI - Pulmonary embolism presenting as fever in spinal cord injury patients: report of two cases and review of the literature. AB - Pulmonary embolism is a common, sometimes fatal complication of spinal cord injury. We describe two quadriplegic patients who developed unexplained fever as the sole presenting sign of multiple pulmonary emboli during the subacute phase following injury. These cases and a review of the literature suggest that ventilation-perfusion scanning should be considered in the diagnostic evaluation of fever in patients with recent spinal cord injury even in the absence of other clinical signs of thromboembolic disease. PMID- 8366338 TI - Urologic aspects of traumatic central cord syndrome. AB - Central cord syndrome (CCS) is a subset of spinal cord injury, characterized by more motor involvement of the upper extremities than the lower extremities and sacral sensory sparing. Patients with central cord syndrome have been reported to have a good rehabilitation and urologic outcome. Our purpose was to assess the urologic outcome in a group of patients with central cord syndrome. We reviewed 23 patients with central cord syndrome who were admitted to Hines VA Hospital between 1983 and 1991, 20 of whom were older than 50 years of age. Urodynamic studies showed detrusor hyperreflexia with a synergistic EMG in 15 patients and detrusor hyperreflexia with external urethral sphincter dyssynergia (DSD) in five patients. Three patients with no urologic problems were not tested. Bladder sensation was preserved during filling in all patients. At follow-up (median = 2 4 months), 16 patients (70 percent) were voiding, seven of whom required either occasional external or intermittent catheterization; nine were voiding independently. The seven other patients (30 percent) required either continuous external or intermittent catheterization (including the five with DSD). Urologic morbidity in the period after SCI included: urinary tract infections (12), renal (2) and bladder calculi (2), superficial bladder cancer (1), epididymitis (1) and none (6). Fifteen patients (65 percent) were ambulatory at follow-up while four patients needed wheelchairs. Data were not available for the other four patients. Urodynamic studies in three of the wheelchair-bound patients showed that two of them had DSD. Most patients with central cord syndrome have favorable urologic and rehabilitation outcomes and can be managed conservatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366339 TI - Sphincterotomy failure. AB - Our experience with transurethral sphincterotomy in the spinal cord injured population of the Milwaukee VA Medical Center is reviewed. The 10-year retrospective analysis disclosed the operative procedure had to be repeated in nine out of 25 patients. The original success rate of the procedure was high, but significant failure appeared later. Possible mechanisms of failure are outlined. It is suggested that the results might be improved through the use of a bladder neck prosthesis. The latter is under active investigation. PMID- 8366340 TI - Risk assessment for pressure ulcers: an adaptation of the National Pressure Ulcer Advisory Panel risk factors to spinal cord injured patients. AB - To estimate risk factors for pressure ulcers, we developed quantitative definitions for each of the nine general areas of risk outlined by the 1989 National Pressure Ulcer Advisory Panel (NPUAP) and evaluated each of these factors in a group of spinal cord injured patients by means of a retrospective chart review at a spinal cord injury referral center serving the New England area. All patients (n = 364) admitted to the spinal cord injury service between January 1, 1989 and December 31, 1990 were studied. We identified a pressure ulcer in 81 of 364 patients (22.3 percent). In the univariate analyses, pressure ulcers were associated with Frankel groups A to B with an odds ratio (OR) of 5.7 (95 percent confidence interval 2.8 to 11.9), low albumin with an OR of 4.9 (95 percent confidence interval 2.8 to 8.6), low hemoglobin with an OR of 2.5 (95 percent confidence interval 1.5 to 4.1), age > or = 60 years with an OR of 1.9 (95 percent confidence interval 1.2 to 3.2) and three independent measures of co morbidity: Cumulative Illness Rating Scale (CIRS) with an OR of 3.7 (95 percent confidence interval 2.1 to 6.3), Charlson Index with an OR of 2.2 (95 percent confidence interval 1.3 to 3.8), and International Classification of Diseases, Ninth Revision, Clinical Modification count with an OR of 4.2 (95 percent confidence interval 2.4 to 7.2). In the logistic regression model, low albumin, CIRS and Frankel grade A to B and history of pressure ulcers were predictors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366342 TI - The anterior cerebellar vermis: essential involvement in classically conditioned bradycardia in the rabbit. AB - The effects of lesions of the cerebellum on the acquisition and retention of aversive Pavlovian conditioned bradycardia were examined in rabbits. Lesions of the anterior cerebellar vermis severely attenuated the acquisition of simple conditioned bradycardia without disrupting baseline heart rate (HR), or unconditioned HR responses. Also, lesions of the vermis performed after the acquisition of conditioned bradycardia eliminated evidence of prior conditioning. Bilateral lesions of the cerebellar hemispheres did not affect conditioned or unconditioned HR responses. These results were interpreted to indicate that anterior vermis lesions specifically disrupted part of an essential conditioned response pathway without interfering with the neural circuits that mediate unconditioned HR responding. These lesion data, coupled with recent electrophysiological evidence of learning-related changes in neuronal activity within the anterior vermis of the fear-conditioned rabbit, suggest that the anterior cerebellar vermis is critically involved in the acquisition and retention of this rapidly learned autonomic conditioned response. PMID- 8366341 TI - Insulin-like receptor and insulin-like peptide are localized at neuromuscular junctions in Drosophila. AB - Insulin and insulin-like growth factor (IGF) receptors are members of the tyrosine kinase family of receptors, and are thought to play an important role in the development and differentiation of neurons. Here we report the presence of an insulin-like peptide and an insulin receptor (dInsR) at the body wall neuromuscular junction of developing Drosophila larvae. dInsR-like immunoreactivity was found in all body wall muscles at the motor nerve branching regions, where it surrounded synaptic boutons. The identity of this immunoreactivity as a dInsR was confirmed by two additional schemes, in vivo binding of labeled insulin and immunolocalization of phosphotyrosine. Both methods produced staining patterns markedly similar to dInsR-like immunoreactivity. The presence of a dInsR in whole larvae was also shown by receptor binding assays. This receptor was more specific for insulin (> 25-fold) than for IGF II, and did not appear to bind IGF I. Among the 30 muscle fibers per hemisegment, insulin-like immunoreactivity was found only on one fiber, and was localized to a subset of morphologically distinct synaptic boutons. Staining in the CNS was limited to several cell bodies in the brain lobes and in a segmental pattern throughout most of the abdominal ganglia, as well as in varicosities along the neuropil areas of the ventral ganglion and brain lobes. Insulin-like peptide and dInsR were first detected by early larval development, well after neuromuscular transmission begins. The developmental significance of an insulin like peptide and its receptor at the neuromuscular junction is discussed. PMID- 8366343 TI - Postmitotic expression of ankyrinR and beta R-spectrin in discrete neuronal populations of the rat brain. AB - Isoforms of ankyrin (ankyrinR) are expressed in both the erythrocyte and the brain. Four cDNAs representing regulatory domains of ankyrinR expressed in the rat spleen and brain were cloned and sequenced. These different cDNAs were found to result from tissue-specific alternative mRNA processing of the ankyrinR regulatory domain. One of the isolated cDNAs was used to develop an antibody to brain isoforms of ankyrinR, and this antibody was used to study the localization of ankyrinR in the rat brain. The protein was found to be widely expressed in neurons of the metencephalon but limited to a discrete subset of neurons in the rat forebrain. In the thalamus and areas of the basal ganglia, these neurons were grouped in defined nuclei, whereas in the cortex, hippocampus, and caudate putamen they appeared as isolated cells distributed randomly throughout these structures. A similar study using an antibody raised against erythrocyte spectrin (beta R) showed a comparable localization to that of ankyrinR. Both proteins were expressed late in the developing rat brain, as part of the maturation stage of neural development. These data suggest a specific role for these erythrocyte structural proteins in the postmitotic development of a subset of neurons in the rat brain. PMID- 8366344 TI - Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1. AB - Recent physiological work has used quantal analysis to investigate the properties of synaptic transmission and long-term potentiation in hippocampal area CA1. These analyses have revealed changes in the strength of excitatory post-synaptic responses following long-term potentiation that could be mediated by cellular mechanisms in the presynaptic element, in the postsynaptic element, or in both elements. In these studies, either minimal stimulation, presumably involving a single presynaptic axon, or recordings from pairs of CA3 and CA1 cells have been used. Interpretation of these quantal analyses requires knowledge about whether single or multiple synapses occur between the presynaptic axon and its target CA1 pyramidal cells. Here, light and serial electron microscopy was used to begin to examine this question and a related question concerning the ultrastructure of spines on multiple-synapse boutons. Light microscopic analyses of Golgi preparations revealed that about 20% of the axons occurring in stratum radiatum come into close apposition with two to four different dendrites of a target CA1 cell. An "apposition" was defined as a point where the axons and dendrites crossed in the same focal plane and therefore were sufficiently close to allow a dendritic spine to reach the axon and possibly establish a synaptic contact. An additional 4% of the axons wound back and forth across individual dendrites, possibly forming multiple synapses closely spaced along the dendrites. Serial electron microscopy revealed that 24% of the individual axonal boutons in stratum radiatum make synapses with multiple dendritic spines arising from either the same or different dendritic segments. Two adjacent boutons of the same axon could also be found to synapse with different spines of the same dendrite. Together with the light microscopic analysis, these observations suggest that multiple synapses occur between single axons in stratum radiatum and their target CA1 cells, and that at least some of these synapses may occur at different electronic distances. If these multiple synapses have different physiological strengths, then they may obscure or smooth peaks in the frequency histograms that are used for quantal analyses. A three-dimensional analysis was done to compare the dimensions of pairs of dendritic spines synapsing with individual axonal boutons. When the pairs of spines associated with a single bouton arose from different dendrites, at least some of which were likely to have come from different cells, the differences between their volumes and the areas of the postsynaptic densities were on average 100% and ranged up to 650%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8366345 TI - Contact-mediated mechanisms of motor axon segmentation. AB - In the chick embryo, the segmental pattern of motor outgrowth depends on guidance cues provided by sclerotome cells. Motor axons preferentially invade the anterior sclerotome but avoid the posterior sclerotome. To determine how motor growth cone motility is influenced by these cells, we used videomicroscopy to analyze the behavior of motor growth cones as they confronted identified sclerotome cells in vitro. After contact, motor growth cones invariably avoided posterior sclerotome cells by either branching or turning. Both types of avoidance behavior were initiated by a local inhibition of veil protrusion: veils failed to progress along the contacting filopodia. This inhibition was specific to veils since contact failed to alter the number of filopodia protruded. Moreover, motor growth cones turned away from posterior cells despite more persistent filopodial contacts with these cells than with the laminin substratum. In no case did contact with posterior cells cause a complete loss of growth cone motility or a complete collapse of growth cone structure. In contrast, motor growth cones exhibited a selective affinity for anterior cells, preferring the surfaces of these cells to the laminin substratum. Contact with anterior cells stimulated a generalized increase in protrusive activity: contact caused a net increase in the extension of veils and filopodia both locally and at sites distant from the site of contact. Contact also elicited a localized thickening of contacting processes, suggesting that contact with anterior cells promotes neurite consolidation. This behavior of motor growth cones in vitro suggests that both an inhibition of veil formation by posterior cells and an enhancement of motility and axon consolidation by anterior cells contribute to the preferential advance of motor axons into anterior sclerotome in vivo. We suggest that patterned outgrowth results from the juxtaposition of two contrasting environments that differentially influence growth cone motility. PMID- 8366346 TI - Spatial and behavioral correlates of striatal neurons in rats performing a self initiated navigation task. AB - To investigate the spatial and behavioral correlates of striatal neurons during displacement movements, the rostromedial dorsal striata (AP 1.0-2.2, ML 1.5-2.0) of five rats were surgically implanted with advanceable bundles of fine wire electrodes. After recovery, the rats were deprived of water and trained in a square-walled open field in a dark room. The behavioral task required alternating visits to water reservoirs in the center and in the four corners. A certain corner contained the first reward for each trial; after this reward, a cue card appeared in this corner for the rest of the trial. The firing rates of striatal units were compared as the rat moved between the center and the four corners of the arena. Analyses were made of 30 units. Eight of these had firing rates that significantly increased or decreased by 62-480% while the rat was in one or more quadrants of the arena. Six of these manifested such firing rate changes only as the rat performed certain behavioral sequences in the quadrant. Three other units fired as the rat's head was in a certain orientation relative to the arena walls, in all parts of the arena. To determine the principal controlling cues and hence the frame of reference of spatial selectivity of these units, the arena, while the rat was still inside, was rotated in total darkness. The first water reward was then presented at the same position relative to the outside room as before the rotation. The cue card was then illuminated in this corner as a visual cue for the extra-arena reference frame. All 11 neurons demonstrated spatial selectivity that rotated with the arena; thus, this activity was in the frame of reference of the arena and was not controlled by the visual cue. Six other units fired at rates up to six times their resting discharge or stopped firing completely in synchrony with initiation or execution of displacement movements, and two of these were also location selective. Four other units were silent as the rat performed the task, but fired tonically following arena rotations or other interruptions of the session, independent of the rat's location or movements. Nine analyzed units had very low firing rates (< 1 impulse/sec) and showed no discernible changes in activity as the rat performed the task. These patterns of unit activity indicate that fundamental informational components required for navigation are coded in the striatum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8366347 TI - Cholinergic regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) but not neurotrophin-3 (NT-3) mRNA levels in the developing rat hippocampus. AB - In previous experiments it has been demonstrated that the synthesis of BDNF (brain-derived neurotrophic factor) and NGF in neurons of the hippocampus is regulated by neuronal activity. The glutamate system is predominantly responsible for upregulation and the GABAergic system for downregulation both in vitro and in vivo (Zafra et al., 1990, 1991). The aim of the present study is to examine the extent to which the cholinergic system is also involved in the regulation of NGF and BDNF mRNA and whether the regulatory contribution of the cholinergic system changes during development. Partial transection of the fimbria fornix bundle in the second postnatal week resulted in a reduction of BDNF and NGF mRNA levels in the hippocampus, suggesting that septal cholinergic input is involved in the regulation of hippocampal BDNF and NGF mRNA levels. Because the fimbria fornix bundle also contains fibers other than cholinergic ones, we further evaluated the importance of the cholinergic influence by injecting pilocarpine, a muscarinic agonist. Pilocarpine markedly increased hippocampal BDNF and NGF mRNA levels in both early postnatal and adult rats. In situ hybridization experiments demonstrated that pilocarpine led to an increase in BDNF expression in the CA1 CA4 regions of the hippocampus and in the dentate gyrus. However, pilocarpine increased NGF mRNA only in those neurons of the dentate gyrus and CA1-CA4 regions that also expressed NGF mRNA in the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366348 TI - A role for postsynaptic neurons in determining presynaptic release properties in the cricket CNS: evidence for retrograde control of facilitation. AB - Intracellular recording sin the cricket cercal system show that the synaptic terminals of a single sensory neuron can facilitate at one target, the medial giant interneuron (MGI), and simultaneously depress at another target, interneuron 10-3. A quantal analysis of transmission at these synapses demonstrates that facilitation and depression are properties of the presynaptic cell. For facilitating synapses contacting MGI, the mean quantal content (m), determined from the probability of the failures, increases for the second EPSP, while the quantal size (q) remains constant. Similarly, an analysis of depression for those synapses contacting 10-3 supports a presynaptic mechanism for depression. Since facilitation and depression are presynaptic and their expression at the synapses of a single, identified sensory neuron are correlated with the target interneuron, we conclude that these properties are regulated locally, at the synapse, possibly by an interaction with the postsynaptic cell. PMID- 8366349 TI - Transplanted neocortical neurons migrate selectively into regions of neuronal degeneration produced by chromophore-targeted laser photolysis. AB - Selective degeneration of neocortical callosal pyramidal neurons by noninvasive laser illumination was used for directed studies of neocortical transplantation, to test the hypothesis that transplanted embryonic neurons may seek to restore normal cytoarchitecture within an appropriately permissive local environment. At long wavelengths that penetrate through tissue without major absorption, photolysis can cause extremely selective degeneration to desired subpopulations of targeted neurons in vivo (Macklis and Madison, 1991; Madison and Macklis, 1993). Cell death is geographically defined and slowly progressive, allowing control over the anatomical substrate for transplantation. Targeting occurs by retrograde incorporation of cytolytic chromophores that are activated by specific wavelength light. Intermixed neurons, glia, axons, blood vessels, and connective tissue remain intact. Degeneration was effected within neocortical lamina II/III of neonatal mouse pups following targeting in utero or early postnatally with photoactive nanospheres. Total neuron density was reduced typically by 25-30% within defined areas, with approximately 60% loss of large projection neurons and no change in the number of small, presumptive interneurons. Embryonic day 17 neocortical cell suspensions, which included recently postmitotic neurons destined to form lamina II/III, were transplanted lateral to these regions of ongoing neuron degeneration in juvenile mice. Cellular injections spanned laminae II-V, to provide donor neurons with both lateral and laminar choice for possible migration and integration. Donor cells were labeled in vitro with unique fluorescent and electron-dense nanospheres that allowed distinct identification of donor cells at both light and electron microscopic levels. Control experiments included neocortical transplants into intact age-matched hosts, into hosts with kainic acid lesions to neocortex, or distant to the region of photolytic neuronal degeneration; embryonic cerebellar transplants to the regions of selective photolytic degeneration; and grafts of hypoosmotically lysed neocortical cells to lesioned regions. After survival times of 1 hr to 12 weeks, labeled neurons were identified morphologically and positions were digitized for qualitative and quantitative analysis of position and specificity of migration and cellular integration; electron microscopy was used to confirm further the donor identities of migrated neurons. Neurons placed near host zones of photolytic neuron degeneration migrated up to 780 microns specifically within these zones; approximately 44% of donor neurons migrated significantly beyond the injection site to enter these regions. Migration and integration did not occur in normal, unaffected deeper layers IV-VI of these experimental mice, or in the normal lamina II/III bordering the transplantation site on the side opposite the neuron deficient region. Control grafts of all five types revealed only minimal local spread without laminar preference.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8366350 TI - Synaptotagmin: a membrane constituent of neuropeptide-containing large dense-core vesicles. AB - Synaptotagmin is known to be a major membrane protein of synaptic vesicles (SVs) in neurons. We have now used an immunoisolation procedure to demonstrate that synaptotagmin is also present in the membranes of peptide containing large dense core vesicles (LDCVs) of rat hypothalamus and bovine posterior pituitary. Synaptotagmin bead-immunoisolated organelles from these tissues primarily consisted of SVs but contained occasionally larger structures reminiscent of LDCVs that were absent from vesicle populations immunoisolated with a synaptophysin antibody. Furthermore, the vesicles immunoisolated with synaptotagmin beads contained significant amounts of neuropeptide Y (NPY). In contrast, vesicles immunoisolated with synaptophysin beads did not contain detectable levels of NPY. Sucrose density gradient fractionation of postnuclear supernatants obtained from the bovine posterior pituitary resulted in a bimodal distribution of synaptotagmin, corresponding to the positions of both SVs and neurosecretory granules. A similar distribution was found for cytochrome b561 and the 116 kDa subunit of the vacuolar proton pump. In contrast, the SV proteins synaptophysin, SV2, and p29 were restricted to the SV-containing fractions. Immunoisolation of small and large vesicles from the sucrose gradient confirmed the differential distribution of synaptotagmin and synaptophysin in the two types of secretory vesicles in nerve endings of the posterior pituitary. We conclude that synaptotagmin is a constituent of both SVs and peptide-containing secretory vesicles in the nervous system. Since both types of organelles undergo Ca(2+) dependent exocytosis, these findings support a general role of synaptotagmin as an exocytotic Ca2+ receptor. PMID- 8366351 TI - Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions. AB - The hippocampus plays an essential role in spatial learning. To investigate whether the whole structure is equally important, we compared the effects of variously sized and localized hippocampal aspiration lesions on spatial learning in a Morris water maze. The volume of all hippocampal lesions was determined. Dorsal hippocampal lesions consistently impaired spatial learning more than equally large ventral lesions. The dorsal lesions had to be larger than 20% of the total hippocampal volume to prolong final escape latencies. The acquisition rate and precision on a probe test without platform were sensitive to even smaller dorsal lesions. The degree of impairment correlated with the lesion volume. In contrast, the lesions of the ventral half of the hippocampus spared both the rate and the precision of learning unless nearly all of the ventral half was removed. There was no significant effect of the location (dorsal or ventral) of damage to the overlying neocortex only. In conclusion, the dorsal half of the hippocampus appears more important for spatial learning than the ventral half. The spatial learning ability seems related to the amount of damaged dorsal hippocampal tissue, with a threshold at about 20% of the total hippocampal volume, under which normal learning can occur. PMID- 8366352 TI - Evidence for in vivo interactions between neuropeptide Y-related peptides and sigma receptors in the mouse hippocampal formation. AB - Recently, it was proposed that neuropeptide Y (NPY) and peptide YY (PYY) could act as endogenous ligands for sigma binding sites, as both NPY and PYY competed with high affinity (nanomolar) for 3H-(+)SKF 10,047 binding sites in rat brain membrane homogenates (Roman et al., 1989). However, various laboratories failed to replicate these in vitro findings. In order to clarify this apparent discrepancy and investigate further possible interactions between NPY and sigma related sites, we evaluated the effects of NPY, PYY and homologs, as well as nonrelated peptides, on in vivo 3H-(+)SKF 10,047 binding parameters in the mouse hippocampal formation. As expected, haloperidol (2 mg/kg), a prototypical sigma receptor ligand, competed for 90% of in vivo hippocampal labeling observed following a peripheral intravenous injection of 3H-(+)SKF 10,047. Intracerebroventricular injections of 300-3000 pmol of either NPY, PYY, NPY2-36, or the Y1 agonist Leu31,Pro34-NPY inhibited significant proportions (17-35%) of haloperidol-sensitive in vivo 3H-(+)SKF 10,047 hippocampal labeling. However, a Y2 receptor agonist, NPY13-36, and nonrelated peptides such as neurotensin and vasoactive intestinal polypeptide, as well as adrenalin, failed to alter in vivo 3H-(+)SKF 10,047 hippocampal binding. It thus appears that NPY, PYY, and a selective Y1 agonist can interact in a concentration-dependent manner, with in vivo 3H-(+)SKF 10,047 labeling in the mouse hippocampal formation. This effect demonstrates selectivity as a Y2 agonist, unrelated peptides, and adrenalin failed to alter in vivo sigma labeling. This in vivo interaction may be relevant to some of the respective biological actions of NPY and sigma-related molecules. PMID- 8366353 TI - Topographic patterns of brain activity in response to swim stress: assessment by 2-deoxyglucose uptake and expression of Fos-like immunoreactivity. AB - Alterations in brain activity patterns were assessed in response to swim stress by immunocytochemical detection of Fos-like immunoreactivity (Fos-LI) and high resolution autoradiographic imaging of 14C-2-deoxyglucose (2-DG) uptake. The stress paradigm investigated was a classic behavioral screen for antidepressant drug activity, the forced swim test. One of the most pronounced effects produced by swim stress was an increase in 2-DG uptake and induction of Fos-LI in a restricted region of the lateral septal nucleus. Specific "limbic" cortical regions, including the medial prefrontal, ventrolateral orbital, and cingulate cortices, also exhibited both increased 2-DG uptake and expression of Fos-LI in response to swim stress. In the hypothalamic paraventricular nucleus of swim stressed rats, Fos-LI was induced but no change in 2-DG uptake was apparent. Since the specific swim stress protocol used is a behavioral screen for antidepressant drugs, the effects of imipramine on stress-induced alterations in 2-DG uptake and induction of Fos-LI were examined. The stress-induced increase in 2-DG uptake in the lateral septum was blocked by treatment with imipramine, but treatment with imipramine had no effect on induction of Fos-LI in the same region. Neither 2-DG uptake nor Fos-LI expression was altered by imipramine treatment in the cortical regions influenced by swim stress. Administration of imipramine alone under basal conditions produced a robust induction of Fos-LI in the central nucleus of the amygdala and in the dorsal lateral subdivision of the bed nucleus of the stria terminalis. No effect of imipramine treatment on 2-DG uptake was apparent in these latter regions. The results provide insights into topographic patterns of brain activity associated with swim stress and neuroanatomically selective actions of imipramine. The different and complementary information obtained by assessment of Fos-LI and 2-DG uptake illustrates the utility of applying both functional mapping approaches to examine neuroanatomical correlates of behavioral states and drug treatment. PMID- 8366355 TI - Vulnerability of mossy fiber targets in the rat hippocampus to forebrain ischemia. AB - Much of the work on forebrain ischemia in the hippocampus has focused on the phenomenon of delayed neuronal death in CA1. It is established that dentate granule cells and CA3 pyramidal cells are resistant to ischemia. However, much less is known about interneuronal involvement in CA3 or ischemic injury in the dentate hilus other than the fact that somatostatin neurons in the latter lose their immunoreactivity. We combined two sensitive methods--heat-shock protein (HSP72) immunocytochemistry and a newly developed Gallyas silver stain for demonstrating impaired cytoskeletal elements--to investigate the extent of ischemic damage to CA3 and the dentate hilus using the four-vessel-occlusion model for inducing forebrain ischemia. HSP72-like immunoreactivity was induced in neuronal populations previously shown to be vulnerable to ischemia. In addition, a distinct subset of interneurons in CA3 was also extremely sensitive to ischemia, even more so than the CA1 pyramidal cells. These neurons are located in the stratum lucidum of CA3 and possess a very high density of dendritic spines. In silver preparations, they were among the first to be impregnated as "dark" neurons, before CA1 pyramidal cells; microglial reaction was also initiated first in the stratum lucidum of CA3. Whereas CA1 damage was most prominent in the septal half of the hippocampus, hilar and CA3 interneuronal damage had a more extensive dorsoventral distribution. Our results also show a far greater extent of damage in hilar neurons than previously reported. At least four hilar cell types were consistently compromised: mossy cells, spiny fusiform cells, sparsely spiny fusiform cells, and long-spined multipolar cells. A common denominator of the injured neurons in CA3 and the hilus was the presence of spines on their dendrites, which in large part accounted for the far greater number of mossy fiber terminals they receive than their non-spiny neighbors. We suggest that the differential vulnerability of neuronal subtypes in these two regions may be attributed to their extremely dense innervation by the mossy fibers and/or the presence of non-NMDA receptor subtypes that are highly permeable to calcium. In addition, early impairment of these spiny CA3 cells and hilar neurons after ischemia may be causal to delayed neuronal death in the CA1 pyramidal cells. PMID- 8366354 TI - Acetylcholine synthesis and release following continuous intracerebral administration of NGF in adult and aged Fischer-344 rats. AB - NGF promotes the survival and enhances the neurotransmitter phenotype of basal forebrain and striatal cholinergic neurons in brain of rat. The objective of the present study was to determine whether stimulations of the cholinergic neuronal markers ChAT and high-affinity choline uptake are reflected in enhanced synthesis and release of ACh. Enhancement of ACh release in brain of adult and aged rats could result in increased cholinergic neurotransmission, and altered animal behavior. NGF (1.2 micrograms/d) was administered intracerebroventricularly for 2 weeks by osmotic minipump to male Fischer-344 rats aged 4 and 24 months. Cholinergic neuronal functional parameters were measured in frontal cortex, hippocampus, and striatum. In young adult rats, increased ChAT and choline uptake activities were accompanied by enhanced ACh synthesis, basal and depolarization induced release of both endogenous and newly synthesized transmitter, with the largest effect generally being observed in striatum. In aged animals, the responses to NGF were less uniform. Whereas the pattern for changes in ChAT activity was similar to that seen in younger animals, choline uptake activity was increased only in frontal cortex and striatum. Coincidentally, ACh synthesis was also increased only in these two brain regions. ACh content of synaptosomes was not affected by age or NGF treatment, and the ACh levels in microwaved samples of striatum and basal forebrain were not affected by NGF treatment. However, profound deficits in both basal and evoked release of newly synthesized ACh were observed in the aged rats. NGF treatment had no significant effect on the basal release of newly synthesized ACh in aged rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366356 TI - Synaptic events that generate fast oscillations in piriform cortex. AB - Prominent, odor-evoked, fast (40-60 Hz) oscillations have been reported in the olfactory bulb and piriform (primary olfactory) cortex of both awake-behaving and anesthetized animals. The present study used current source-density analysis to examine the origin of the fast oscillations evoked by single weak shocks to afferent fibers. These shock-evoked oscillations closely resemble those evoked by odor. The results revealed that each cycle of the oscillatory field potential was generated by a stereotyped series of membrane currents similar to those previously characterized in the nonoscillatory response to strong afferent fiber shocks. Each cycle began with a strong inward current in layer la identified as an EPSC mediated by afferent fibers in distal apical dendrites of pyramidal cells. This afferent input was followed by a strong inward current in layer Ib identified as an EPSC mediated by intrinsic association fibers in middle apical dendritic segments. These excitatory events were followed by a smaller inward current at the depth of pyramidal cell somata (layers II and superficial III) that may be the depolarizing Cl(-)-mediated IPSC previously identified in the strong-shock response. Based on an analysis of the timing of the EPSCs it was concluded that the weak shock-evoked oscillation is generated in the olfactory bulb and that the resulting periodic activity in afferent fibers drives the oscillation in the piriform cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366357 TI - Directionally selective mnemonic properties of neurons in the lateral dorsal nucleus of the thalamus of rats. AB - The hippocampal formation has been extensively studied for its special role in visual spatial learning and navigation. To ascertain the nature of the associations made, or computations performed, by hippocampus, it is important to delineate the functional contributions of its afferents. Therefore, single units were recorded in the lateral dorsal nucleus of the thalamus (LDN) as rats performed multiple trials on a radial maze. Many LDN neurons selectively discharged when an animal's head was aligned along particular directions in space, irrespective of its location in the test room. These direction-sensitive cells were localized to the dorsal aspect of the caudal two-thirds of the LDN, the site of innervation by retinal recipient pretectal and intermediate/deep layer superior colliculus cells (Thompson and Robertson, 1987b). The directional specificity and preference of LDN cells were disrupted if rats were placed on the maze in darkness. If the room light was then turned on, the original preference was restored. If the light was again turned off, directional firing was maintained briefly. Normal directional firing lasted about 2-3 min. After this time, the directional preference (but not specificity) appeared to "rotate" systematically in either the clockwise or counterclockwise direction. The duration of normal directional discharge patterns in darkness could be extended to 30 min by varying the behavior of the animal. LDN cells required visual input to initialize reliable directional firing. After the rat viewed the environment, directional specificity was maintained in the absence of visual cues. Maximal directional firing was achieved only when the rat viewed the entire test room, and not just the scene associated with the directional preference of the cell. Thus, contextual information seems important. Also, a significant correlation was found between directional specificity and errors made on the maze during acquisition of the task. It was concluded that the LDN may pass on to the hippocampal formation directional information that is not merely a reflection of current sensory input. As such, the LDN may serve an important integrative function for limbic spatial learning systems. PMID- 8366358 TI - Neurotrophin receptor genes are expressed in distinct patterns in developing dorsal root ganglia. AB - All members of the neurotrophin family of neuronal growth factors promote survival and neurite outgrowth of dorsal root ganglion (DRG) neurons in vitro. The trk family of protooncogenes encodes receptors that are now thought to mediate the biological effects of neurotrophins. In order to learn more about the dependence of DRG neurons on neurotrophins in vivo, we have studied mRNA expression of members of the trk family in developing DRGs in embryonic and postnatal rats. We show here that neurotrophin receptors are expressed in thoracic and lumbar DRGs by embryonic day 13 (E13), which is only 24-48 hr after neurogenesis begins in these ganglia. Distinct patterns of expression of trkA, trkB, and trkC are readily apparent by E15. At this age, 40% of thoracic DRG neurons express trkA. In contrast, trkB and trkC are expressed by only 6% and 8%, respectively, of thoracic DRG neurons. These percentages change little between E15 and postnatal day 1. Although absolute numbers of DRG neurons expressing neurotrophin receptors are greater in lumbar than in thoracic ganglia, the ratios of DRG neurons expressing different members of the trk family are similar in the two regions. The different trks are expressed by distinct populations of DRG neurons from E15 onward. trkA is expressed predominantly by small neurons with darkly staining cytoplasm. trkB and trkC are expressed by large, lightly staining neurons. Size-frequency histograms show that trkA is expressed by neurons of variable sizes, but particularly by neurons at the smallest end of the spectrum. In contrast, trkC is expressed predominantly by large DRG neurons, including those with the largest soma areas. trkB is expressed by DRG neurons of intermediate size. Our results show that a majority of DRG neurons express mRNA for at least one member of the trk protooncogene family. Furthermore, trk expression occurs in a time frame consistent with the idea that trks mediate responses of DRG neurons to neurotrophins that are synthesized in both the periphery and spinal cord at early developmental stages. Finally, different populations of DRG neurons express different trks. We hypothesize that DRG neurons subserving different functions express different trks, and that trk expression of a particular class of DRG neurons determines its neurotrophin dependence during development. PMID- 8366359 TI - Rescue of axotomized immature rat facial motoneurons by R(-)-deprenyl: stereospecificity and independence from monoamine oxidase inhibition. AB - The role of monoamine oxidase B (MAO-B) in R(-)-deprenyl-mediated rescue of rat facial motoneurons axotomized at postnatal day 14 (P14) was investigated using the (+)- and (-)-enantiomers of deprenyl [S(+)-deprenyl and R(-)-deprenyl]. Previously, doses of R(-)-deprenyl sufficient to inhibit MAO-B were shown to increase the survival of motoneurons following an apparent loss of target-derived trophic support caused by axotomy in P14 rats. In the present experiments, motoneuronal survival was measured 21 d after unilateral facial nerve transection at P14. The animals were treated with saline or doses of R(-)- or S(+)-deprenyl ranging from 0.001 to 10 mg/kg every 2 days (/2d). Frontal serial 10 microns sections were taken through the length of the facial nuclei ipsilaterally and contralaterally to the facial nerve transections. Every third section was immunoreacted for an antibody against ChAT to identify the motoneuron somata, while every adjacent third section was Nissl stained to assess motoneuronal survival. A second series of P14 rats was treated with similar doses of the two deprenyl enantiomers or saline and the brainstems removed for measurement of MAO A and MAO-B activity at 4 hr after the treatments. Averages of 24% of the facial motoneurons survived axotomy with either saline treatment or 0.001 mg/kg/2d doses of R(-)-deprenyl. Doses of R(-)-deprenyl of 0.005, 0.01, and 10.0 mg/kg/2d increased the surviving facial motoneuron to 38%, 51%, and 48%, respectively, indicating an ED50 of about 0.005 mg/kg/2d. Doses of S(+)-deprenyl as high as 10 mg/kg/2d did not increase motoneuronal survival, revealing a stereospecificity for the increased survival of at least 2000-fold. The ED50 for MAO-B inhibition in the P14 brainstem was approximately 0.1 mg/kg for the (-)-enantiomer and 2.0 mg/kg for the (+)-enantiomer, revealing a 20-fold higher sensitivity of the enzyme toward the (-)-enantiomer in the P14 rat brainstem. A dose of 10 mg/kg of S(+)-deprenyl inhibited about 65% of brainstem MAO-B activity without increasing motoneuronal survival, whereas 0.005 and 0.01 mg/kg of R(-)-deprenyl increased motoneuronal survival without significant inhibition of brainstem MAO-B activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8366360 TI - Nonuniform expression of habituation in the activity of distinct classes of neurons in the Aplysia abdominal ganglion. AB - Global observations of neuronal response in the Aplysia abdominal ganglion were made during habituation of the gill withdrawal reflex using voltage-sensitive dye recording. This technique makes it possible to measure the spike activity of 30 50% of the 1000 neurons present in the ganglion. Our experiments address the issue of how habituation is expressed in the activity of the population of neurons responding to siphon stimulation. Several classes of neurons exhibited characteristically distinct responses to the stimuli and to habituation training. One class of neurons (group I) responded to the onset and offset of the sensory stimulus although they are probably not primary sensory neurons. They habituate only partially when the behavioral reflex has already habituated completely. Two other classes (groups II and III) both have sustained responses to the touch, but habituate differently. Members of group III habituate completely while those in group II habituate only partially. Another class of neurons are inhibited by the stimulus (group IV). They become less inhibited after habituation. The response of both group I and group IV are new classes of response that have not been previously reported. PMID- 8366361 TI - Corticosteroid actions on amino acid-mediated transmission in rat CA1 hippocampal cells. AB - We here describe actions mediated by mineralo- and glucocorticoid receptors (MRs and GRs, respectively) on intracellularly recorded synaptic responses, evoked in rat CA1 pyramidal cells in vitro by stimulation of the Schaffer collaterals. Neurons in slices from adrenalectomized (ADX) rats, that is, where MRs and GRs are unoccupied, showed a synaptic response consisting of an EPSP, followed by a fast and a slow IPSP; the responses were apparently similar to those in slices from sham-operated rats. However, in the ADX rats, repeated electrical stimulation over a period of 80 min resulted in a gradual decline of the firing probability for synaptically driven action potentials and of the slow IPSP amplitude. Nonsynaptic responses (e.g., membrane potential, accommodation, and afterhyperpolarization) were stable during the 80 min period. Application of 3 nM aldosterone between 20 and 40 min after impalement of cells in slices from ADX rats, thus activating predominantly MRs, yielded stable synaptic and nonsynaptic responses for at least 1 hr after the onset of the steroid application. By contrast, corticosterone (30 nM), which occupies GRs in addition to MRs, reduced the amplitude of both the EPSP and slow IPSP, and the firing probability of synaptically driven action potentials, within 20 min; nonsynaptic properties remained stable. Similar results were obtained with the selective glucocorticoid RU 28362. The EPSP and fast and slow IPSPs of neurons in slices from ADX rats impaled with a time lag of 1-4 hr after the steroid application did not differ significantly from the responses of neurons impaled before steroid application.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366362 TI - Unexpected presence of neurofilaments in axon-bearing horizontal cells of the mammalian retina. AB - In several mammals only one of the two types of retinal horizontal cell, the axonless A-type, appears to express neurofilaments. Neurofilament immunostaining of rodent retinas reveals a horizontal cell plexus that has previously been interpreted as belonging to A-type cells. Our intracellular Lucifer yellow injections strongly suggest that there are no A-type horizontal cells in rat and gerbil. Counterstaining of dye-injected cellular structures with a neurofilament antibody directly shows that the axon terminal systems of the axon-bearing B-type horizontal cells contain neurofilaments. These unexpected findings explain and reinterpret the neurofilament plexus in rodent retinas. In contrast, Lucifer yellow injections in guinea pig retina reveal both A- and B-type horizontal cells, showing that horizontal cell types are not uniform among rodents. In the guinea pig retina both A-type cells and B-type axon terminal systems contain neurofilaments. PMID- 8366363 TI - Efficacy of ampicillin/sulbactam combination in experimental shunt infections caused by Staphylococcus epidermidis. A light and scanning electron microscope study. AB - In this study, the efficacy of ampicillin/sulbactam combination in reactions of periventricular tissue of the lateral ventricle induced by the presence of infected (Staphylococcus epidermidis) silicone rubber shunt tubing was examined by using light and scanning electron microscopy. It was demonstrated that reactive changes to implants had occurred in periventricular tissue in the control group. In infected shunt tubing without given prophylactic antibiotic group, generalized meningitis and ventriculitis, loss of integrity of ependymal cells, numerous inflammatory cells, bacterial colonies, exuda and even pus were seen. It was also shown that rarely inflammatory reactions, minimal disintegration of ependymal cells, no bacterial colonies, and phagocytes were present in the group which was given prophylactic ampicillin/sulbactam combination per and postoperatively. We think that ampicillin/sulbactam combination is very effective in prevention and treatment of shunt infections. PMID- 8366364 TI - Intracranial aneurysm associated with cerebral cavernous angioma. Case report. AB - The very rare case of association of anterior communicating artery aneurysm and a right frontal cavernoma not visualized by CT-scan and angiography in a 37-year old man is described. The rarity and the possible pathogenesis of this association are discussed. PMID- 8366365 TI - Saccular aneurysm associated with proximal basilar artery fenestration. Case report. AB - When an aneurysm arises from a limb of an arterial fenestration at the vertebrobasilar junction or in the proximal third of the basilar artery, its surgical management can be an intriguing problem. We report here a case of such an aneurysm successfully clipped through a right subtemporal transtentorial approach. PMID- 8366366 TI - Spinal epidural hemangiomas. AB - Two patients with epidural cavernous hemangiomas located at the lumbar and cervical spine are reported. The first case presented clinically as progressive paraparesis, and the second began with sudden tetraparesis after a strong physical exercise. Myelography and MRI were the diagnostic tools. Surgical decompression improved the signs and symptoms in both cases. Spinal epidural cavernous hemangiomas are rare lesions that are usually regarded as vascular hamartomas. Symptom onset may be insidious or acute and the prognosis after timely surgery is better when compared with that of intrathecal cavernous hemangiomas. The histology and treatment of these processes are discussed. PMID- 8366367 TI - Intraethmoidal encephalomeningocele presenting with spontaneous cerebrospinal fluid rhinorrhea in an elderly man. Case report. AB - The case of a 63-year-old patient with spontaneous cerebrospinal fluid rhinorrhea from a intraethmoidal encephalomeningocele is presented. The patient was asymptomatic until the old age. The preoperative coronal CT-scan and the preoperative and postoperative MRI are shown. The rarity of this onset in an elderly man and the surgical indications of this disease are debated. PMID- 8366368 TI - Extradural haematoma of posterior cranial fossa. AB - Two cases of extradural haematoma of posterior fossa with an acute course are reported. After trauma, the two patients did not show any symptom for a time of 16 and 18 hours respectively. Both of them showed a status of coma at the moment of hospitalization. The haematoma was diagnosed by CT scan. Both of them were immediately operated in order to evacuate the haematoma. Afterwards, one of the patients presented cerebellar symptoms while the other did not show any neurologic deficiency. The authors have analysed cases of this rare form of post traumatic pathology referred in the literature since 1941, examining them from a clinical, therapeutic and prognostic point of view. The best diagnostic and therapeutic procedures to follow on this subject are then stressed. PMID- 8366369 TI - Cervical cord compression in hereditary multiple exostoses. AB - A seven year old girl, known to have hereditary multiple exostoses, developed moderate gait disorders at the age of six years. Deterioration of myelopathy initiated the clinical investigation including spinal computed tomography (CT) and magnetic resonance imaging (MRI). These examinations demonstrated a coneshaped exostosis originating from the posterior arch of C2. The spinal canal was markedly narrowed with significant compression of the spinal cord at the C2 level. The girl underwent laminectomy of C2 with total removal of the exostosis. Postoperative deterioration of neurological symptoms correlated with a hypointense lesion on T1 weighted imaging in the cord at the same level, but no further cord compression on follow-up MRI. The spastic tetraparesis has improved considerably within 12 months thereafter. PMID- 8366370 TI - CT morphology of a median nerve neurilemmoma at the arm. Case report and review. AB - Computed tomography was performed in a patient with a median nerve tumor at the arm, histologically confirmed as neurilemmoma. Neurilemmoma was a slightly hypodense, solid tumor with no vascular contrast enhancement. To our knowledge this is the first CT description of a median nerve neurilemmoma at the arm. According to our experience and to previous literature, CT gives useful information regarding extent, anatomic location, size and relationship of peripheral nerve neoplasm to surrounding structures and may be an useful tool for evaluation arm nerve mass and for appropriate planning of surgical therapy. PMID- 8366371 TI - Sequential measurements of cerebral blood flow in the acute phase of subarachnoid hemorrhage. AB - Cerebral blood flow (CBF) measurements were made at predetermined intervals over the first 20 days after a subarachnoid hemorrhage (SAH) by the method of 133Xe inhalation clearance in 39 patients, Hunt and Hess degrees I, II or III. Mean hemispheral and regional blood flow showed a similar pattern of behavior over time: namely an initial hypoperfusion, being more marked in patients with consistent or thick blood deposition at CT scanning, followed by transient improvement and subsequent deterioration in the second week, this being especially conspicuous in patients who developed vasospasm; deterioration, at any rate, was distributed widely regardless of the initial CBF readings or magnitude of bleeding. Patients developing later neurological deficit (23% of the total) were those who showed a statistically significant increase of hemispheric asymmetries and regional hypoperfusion at the time when deterioration occurred. Accordingly, the Author calls attention to the practical value of CBF measurements in SAH patients, in view of the relationships that obtain between certain CBF patterns and the emergence of late neurologic deficits. PMID- 8366372 TI - Use of a conceptual framework in planning and implementing an orientation program. AB - Staff development instructors must provide a complete and cost-effective orientation program for new employees. Using a conceptual framework to organize an orientation program ensures that essential information is covered in a logical, comprehensive way, allowing for the best use of time and resources. This article describes how a preexisting conceptual framework developed for defining patient-care requirements was used to plan and implement a pediatric orientation program. PMID- 8366373 TI - Role efficacy and job satisfaction of hospital nurses. AB - One concern of healthcare professionals today is the high turnover rate of hospital nursing staff. This article discusses role efficacy and its relation to job satisfaction of hospital nurses. It describes a role-efficacy model and analyzes nurses' perceptions of feedback from the job itself, nursing supervisors, physicians, and hospital administrators. The impact of role efficacy and job satisfaction on improved recruitment and retention of nurses and the role of staff development in the improvement process is explained. PMID- 8366374 TI - A reliable and valid evaluation instrument for continuing nursing education. AB - Practitioners in continuing nursing education must develop reliable and valid evaluation instruments to increase their confidence in the quality and usefulness of the information being gathered. In addition, they should consider the requirements for accreditation or approval of their continuing education activities. This article describes the process used by one provider to accomplish these goals. PMID- 8366375 TI - Preceptor selection and evaluation: a tool for educators and managers. AB - The preceptor concept has been cited extensively in the literature, although few measurable tools for preceptor identification, selection, and evaluation have been documented. This article describes a tool designed to assist in the selection of unit preceptors. The tool also provides an evaluation method for preceptors and identifies areas for future preceptor development when used on an annual basis. PMID- 8366376 TI - Proactive versus reactive recruitment and retention strategies. AB - With so many options available to nurses today, it is imperative to recognize the importance of not only recruiting but retaining nurses within the organization as well as the profession. This study identifies recruitment and retention strategies that nurses deem important. Although numerous responses were noted, continuing education was the most frequently cited benefit for recruitment and retention of nurses. PMID- 8366377 TI - A systematic approach to selecting and evaluating instructional materials. AB - This article provides an overview of the process of selecting and evaluating instructional materials. The reader is given specific criteria to be used in assessing the content, instructional design, technical production, and packaging of instructional materials. PMID- 8366378 TI - The 5-minute teaching series. PMID- 8366379 TI - Mandatory education: a successful, creative approach. PMID- 8366380 TI - Data management ... beyond the basics. PMID- 8366382 TI - Support needs of spouses of cardiac patients. AB - A focus group approach was used to determine the perceived support needs of cardiac patients' significant others. Data were gathered during four focus groups of 2-6 people for a total of 13 informants. Two open-ended questions guided the discussion: (a) What was it like for a person to have someone close have a sudden heart problem? (b) What kind of support is needed during the experience? Informants included spouses of cardiac patients who were newly enrolled in a cardiac rehabilitation program. Discussion sessions were tape recorded. Transcripts were analyzed by using grounded theory. Results revealed three core categories: perceptions, needs, and strategies. Categories differed according to three phases of the illness: finding out, hospitalization, and recovery. The model differs in perceptions, needs, and strategies for support in each phase. Nurses can use this model to understand the needs of significant others and plan support interventions. PMID- 8366381 TI - Drug interactions and their nursing implications. AB - Drug interactions occur whenever the diagnostic, preventive, therapeutic, or toxic action of a drug is modified by another substance (food or drug). Drug interactions can be harmful or beneficial. As more drugs are released, the possibility of drug interaction increases daily. Nurses need to be aware of the mechanisms for drug interactions in order to assist with prevention. The general concepts of drug interactions are presented as to the categories of occurrence: pharmacokinetic, pharmacodynamic, combined toxicities; drug-food interactions, and incompatibilities. PMID- 8366384 TI - Bibliography: nursing and technology. PMID- 8366383 TI - Patient adaptation to technology: an application of the Roy model to nursing research. AB - Structured interviews were used to explore 75 medical-surgical patients' reactions to intravenous (invasive) and telemetry (noninvasive) attachment. Dependent variables operationalizing constructs of comfort, self-esteem, patient role, and social relationships derived from Roy's four effector modes were organized into 19 adaptation items. It was hypothesized that patients attached to invasive technology would report more stimuli and need for behavioral responses than those attached to noninvasive technology. In keeping with the exploratory nature of the study and use of a new adaptation interview tool, item-by-item analysis was used to test the hypotheses. Most support for the hypotheses occurred when patients were attached to only one invasive device and for less than 3 days. Findings also provide new insights on how technology connections might put patients at risk for coping difficulties. PMID- 8366386 TI - What are the current recommended guidelines concerning the use of contact lenses in the chemical industry? PMID- 8366385 TI - Surrogate decision-making and ethics committees: the new role of the New York State nurse. AB - "When Others Must Choose: Deciding for Patients Without Capacity" is health care legislation proposed for New York state. Its intent is to remedy the absence of legal authority for families or other surrogates to make treatment decisions for their incapacitated loved ones who have neither completed an advance directive nor designated a health care agent. This paper provides a summary of this legislation and highlights nursing implications and the role of the nurse as a member of institutional ethics committees. PMID- 8366387 TI - Should an x-ray technician with ulcerative colitis be removed from his work because of the possible increased risk of developing colon cancer? PMID- 8366388 TI - Determination of disability. PMID- 8366389 TI - Necrosis after low-pressure injection injury of the hand. PMID- 8366390 TI - The Occupational Safety and Health Administration's 1990-1991 survey of occupational medical surveillance prevalence and type of current practices. AB - For all industry divisions, the likelihood that an establishment will have a medical surveillance program increases directly with size of establishment. Among establishments with 1 to 19 employees, only 4% have medical surveillance programs whereas 56% of establishments that employed 250 or more employees had such programs. The most common time to administer medical surveillance is preemployment. The second most common time to conduct medical surveillance is at periodic intervals. The most common component of medical surveillance programs is a general physical examination. This component of medical surveillance is also the most common element of preemployment surveillance, preplacement surveillance, periodic surveillance, preexit examinations, and surveillance for respirator users. Among the group of Phase II establishments, audiometric testing was the most common periodic test identified. Musculoskeletal testing is performed by 45% of firms administering preplacement examinations and by 38% of firms with preemployment examinations. Across all industry divisions, 14% of establishments that have a medical surveillance program also perform biologic monitoring of some employees. PMID- 8366391 TI - The purposes of occupational medical surveillance in US industry and related health findings. AB - The primary purpose for implementing medical surveillance is to protect the general health and fitness of all employees. The next most frequent purpose of medical surveillance programs is to determine whether employees have the physical capability to perform their jobs (ie, surveillance to establish "fitness for duty"). The most commonly reported uses of medical surveillance data for establishments across all industry divisions were to implement or change work practices, to implement or change administrative control programs, to modify training programs, and to change personal protective equipment. Eighteen percent of establishments in all size classes and industries that have medical surveillance programs have identified adverse health effects among employees. The health effects most commonly identified by the medical surveillance programs were repetitive trauma, hearing loss, and skin disorders. Programs designed to detect hearing loss and cumulative trauma disorders, are in fact, finding these adverse effects. Among employees actually receiving periodic medical surveillance tests (6 million), 5% were found to have an abnormal test result. PMID- 8366392 TI - Effects of occupational medical surveillance programs as perceived by respondents to the Occupational Safety and Health Administration's 1990-1991 survey. AB - Among all establishments perceiving a change as a result of their medical surveillance program, 43% of those employing 250 or more employees did so; for the smallest establishments, this figure drops to 7%. The changes most often perceived, regardless of size class of establishment or industry division, were in employee relations, injury rates, and insurance costs. Establishments with the most comprehensive risk reduction strategies were most likely to attribute benefits to their medical surveillance programs. Benefits of medical surveillance perceived by the Phase II respondents include reduced costs, early detection of medical problems, increased productivity, and a reduced injury or illness rate. Most firms have no systematic method or procedures for evaluating the effectiveness of their medical surveillance programs. PMID- 8366393 TI - Medical surveillance: extent and effectiveness? PMID- 8366394 TI - Occupational chemical exposures in an academic medical center. AB - Although the risks of certain chemical agents in the hospital environment are well known, problems associated with the entire spectrum of chemicals are not. To address this issue, we analyzed incident reports generated in response to chemical exposures in an academic medical center. We also reviewed workers' compensation clinic logs and the OSHA 200 log to obtain information on medical follow-up and severity. A total of 253 exposures occurred during the 3 years from 1988 to 1990. The overall incidence rate was 8.0 per 1000 person-years. Exposure rates by job title were highest for housekeepers (60.1 per 1000 person-years), followed by maintenance workers (18.6), and laboratory technicians (13.1). The most frequently involved chemical groups were disinfectants (25.9%), solvents (16.8%), and cleaning compounds (12.1%). Exposure by the dermal route was most common (37.9%). Thirteen percent of the exposures resulted in lost time and a similar percentage was reported on the OSHA log. Medical treatment was obtained by 53%. Implications for hazard communication, recordkeeping, and prevention are discussed. PMID- 8366395 TI - Working women at risk. Results from a survey of Hispanic injury patients. AB - Women experience lower rates of occupational injury than do men in general, but subgroups are at increased risk. Based on the medical records of 2572 injury patients requesting treatment in a Washington, DC, emergency department during a 1991 survey of injured Hispanics, we found that whereas women in general had a low risk of occupational injury. Hispanic women did not realize this protection. All Hispanics were at increased risk of occupational injury, but the relative risk attributable to ethnicity for Hispanic women (3.83; 95% confidence interval, 2.85,5.14) was nearly twice that of the corresponding relative risk suffered by working Hispanic men (2.07; 95% confidence interval, 1.72,2.48). It was also found that whereas, overall, women had a lower risk of assault than did men, relative risks of assault based on sex were the same in the workplace. PMID- 8366396 TI - Silicosis following employment in the manufacture of silica flour and industrial sand. AB - We describe silicosis in a patient with chronic obstructive pulmonary disease who worked as a maintenance mechanic for less than 5 years in a plant in South Carolina that manufactures silica flour and industrial sand. An open lung biopsy showed an early stage of silicosis manifested by perivascular and peribronchial collections of macrophages as well as early granuloma formation. An antinuclear antibody profile compatible with Sjogren's syndrome or systemic lupus erythematosus occurred with no symptoms of either disease. Excessive occupational exposure levels of respirable free silica were documented. PMID- 8366397 TI - Heat stress and helicopter pilot errors. AB - Helicopter pilots are subjected to degrees of heat stress that under laboratory conditions result in decreased performance. However, the effect of heat stress on the frequency of helicopter pilot errors is uncertain. The purpose of this study is to determine whether there is an association between ambient heat stress and pilot error. The records of 500 helicopter accidents and incidents due to pilot error during the months May through October were selected at random. On the day of the event, ambient dry bulb and wet bulb temperatures were recorded and compared to temperature and humidity readings on 1000 days chosen at random over the same time period, after eliminating days where events occurred. There was a significant difference between the dry temperature distributions of the days with pilot error compared with the control group (chi 2 = 47.54, P < .0001). A dose response relationship was found, with a significantly lower risk when ambient dry bulb temperatures were 25 to 29 degrees C (odds ratio, 0.6; 95% confidence interval, 0.5 to 0.8, P < .0001), an increased risk of 1.6 (1.3 to 2.0, P < .0001) at 30 to 34 degrees C, and the highest risk at 35 degrees C or more (6.2, 95% confidence interval, 2.1 to 21.8, P < .0002). There is a dose-response relationship between ambient heat stress and pilot error in Israel military helicopter pilots. This is the first study outside the laboratory showing a connection between heat stress and accidents due to human error. Further studies are required to substantiate our findings and to determine whether extrapolation to other settings is warranted. PMID- 8366398 TI - [Surgical approach to the nasal valve stenosis]. AB - Nasal valve, originally defined by Mink (1903), has changed its concept and is now regarded as slit-like opening between the caudal end of the upper lateral cartilage and the septum. Contrary to Caucasians whose smallest area of the nose lies at the nasal valve, the narrowest part of Japanese nose situates at the area between the anterior portion of the inferior turbinate and the septum. Thus, we have fewer chance to experience patients with stenotic nasal valve. Six patients complaining nasal obstruction resulted from nasal valve stenosis, mainly due to dislocated or collapsed upper lateral cartilage, underwent surgery during the last 2 years and a half. Cases of septal deformity, even it it produced valve stenosis, were excluded in this study. Surgical intervention was directed toward reconstruction of normal anatomic relationships, usually by widening the nasal valve angle and preventing collapsibility. Three underwent open rhinoplasty with gull-wing columellar skin incision, whereas 3 others were operated on via transnostril approach. History of midfacial trauma caused us to choose open rhinoplasty for restoring the function and structure. Immediate postoperative result was excellent in the aspect of appearance and subjective data regardless of surgical approach. Open rhinoplasty provided a splendid long-term result without remarkable complications. On the other hand, 2 cases operated via transnostril approach complained recurrence of stuffy nose. PMID- 8366399 TI - [Esophageal speech and TE shunt speech--a comparison using the same subjects]. AB - The behaviors of esophageal speech and tracheoesophageal shunt (TE shunt) speech were compared using two laryngectomized subjects who were able to perform both phonation methods. Through X-ray fluorography and fiberscopic observation of the PE segment, it was confirmed that the location and the shape of the vibrating PE segment (pseudoglottis) were consistent during esophageal speech and TE shunt speech in each patient. It was suggested that the mechanism of formation of the pseudoglottis does not differ between the two phonation methods. The aerodynamics were examined using one of the two subjects. There was a positive relationship between subpseudoglottic pressure and vocal pitch and also between subpseudoglottic pressure and pseudoglottic resistance. The vocal pitch and pseudoglottic resistance were significantly higher in esophageal speech than TE shunt speech, when compared within the same subpseudoglottic pressure range. It was suggested that the tension and the effective mass of the pseudoglottis was modulated differently between the two phonation methods. PMID- 8366400 TI - [Acute sensory deafness originating from experimental double-membrane rupture]. AB - Combined rupture of Reissner's membrane and the round window membrane (double membrane rupture) as a cause of acute profound sensorineural hearing loss was investigated in guinea pigs. Action potentials (APs) of the cochlear nerve in response to tone pip stimuli (1, 2, 4, 8kHz) were recorded before and after rupture of Reissner's membrane at each turn of the cochlea. Then the round window was perforated to create leakage of the perilymph. Ninety minutes later, AP was again recorded. After these procedures, the animal was sacrificed for histological study to confirm the rupture of Reissner's membrane. The ears with double-membrane rupture showed a larger decrease in AP amplitude at all test frequencies than did control ears with round window rupture alone. The ears in which Reissner's membrane was ruptured at the second turn showed more a pronounced decrease in AP amplitude than those ruptured at the third and apical turns. It was concluded that double-membrane rupture could be a cause of sudden deafness, but that the disturbance of cochlear function depends on where Reissner's membrane ruptures. PMID- 8366401 TI - [The effect of unilateral nasal patency on the contralateral side]. AB - This investigation was designed to verify the possible feed-back mechanism which works to compensate for changes in the nasal volume of one side by the other side. Acoustic rhinometry, with which nasal volume is easily evaluated, was used in this investigation. Acoustic rhinometry was performed at 4 points in time (immediately after, and three, six and nine minutes after, the setting of experimental conditions). This investigation was composed of two studies. In the first study, ten healthy subjects (nine males and one female, 26-49 years of age, mean age 30 years) were evaluated to estimate the effect of decreased unilateral nasal patency upon the other side. In this study, one nasal cavity was occluded with an acryle plug, and the nasal volume of the other side was evaluated by acoustic rhinometry before and after the occlusion. In the second study eight healthy subjects (five males and three females, 24-34 years of age, mean age 29 years) were evaluated to estimate the effect of increased unilateral nasal patency upon the other side. This study covered a period of three days. A small piece of cotton soaked in a vasoconstrictor solution (1/1000 adrenalin or 0.05% naphazolin nitrate) was put in one nasal cavity (the right on the first day, the left on the second day) and the other side was evaluated before and after administration of the solution. On the third day of the control study, a similar piece of cotton soaked in physiological saline solution was put in one nasal cavity, and the other side was evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366402 TI - [Three patients with gas gangrene of the head and neck]. AB - Three patients with non-clostridial gas gangrene of the neck are reported. Patient 1 was a 57-year-old man, patient 2 a 63-year-old woman, and patient 3 a 44-year-old man. All three were treated by thorough debridement and precise administration of antibiotics. We also discuss 26 cases (including our 3) of gas gangrene of the head and neck, reported in Japan from 1975 to 1992, from which the following data were obtained: 1. The 26 patients consisted of 17 males and 9 females. 2. They ranged in age from 2 to 88 years, with a mean 56.5 years. 3. Causes included acute pharyngolaryngeal inflammation (46%), dental disease (27%), trauma (8%) and unknown etiology (19%). 4. As a result of bacteriological assessment, the condition was found to be attributable to Clostridium in only 2 patients, and in the remainder the condition was non-clostridial. 5. The mortality rate was 15%. The patients who died were at least 80 years old, and their prognosis had been poor. 6. CT was useful for diagnosis and treatment. PMID- 8366403 TI - [Voice rehabilitation with esophageal speech in the laryngectomized]. AB - From January 1988 to December 1990, 186 patients with laryngeal cancer or hypopharyngeal cancer underwent total laryngectomy in our hospital. We studied voice restoration in 110 of these patients by means of a direct interview method at the end of 1991. Seventy-six cases were excluded because of death (70) or being lost to follow-up (6). About 80% of the patients (89/110) attended esophageal speech classes, with a success rate of 78% (69/89). Seventy-four percent (51/69) had no problems with daily oral communication using esophageal speech. Neither radiation therapy nor post operative pharyngocutaneous fistula formation influenced the success rate. Neither did the site of the primary tumor in the larynx or hypopharynx exert an influence, although patients with laryngeal cancer were superior to those with hypopharyngeal cancer in terms of the quality of esophageal speech. It was found that age was the most important factor. Patients below 60 years old had a 90% success rate, between 60 and 75 the rate was 60% and above 75 it was only 10%. Unfortunately, 15% (17/110) of the laryngectomized patients used a pen and pad alone. Most were too old to attend esophageal speech classes. PMID- 8366404 TI - [Changes in transaminase before and after tonsillectomy]. AB - Almost all patients who undergo palatine tonsillectomy for chronic tonsillitis and/or tonsillar hypertrophy manifest postoperative changes in their condition and laboratory data. In some patients, high preoperative transaminase levels decrease postoperatively. I studied 17 patients who had abnormal serum transaminase levels 10 days before tonsillectomy. Before tonsillectomy, serum glutamate oxaloacetate transaminase (GOT) levels were abnormal in half and serum glutamate pyruvate transaminase (GPT) were abnormal in all. Before operation, laboratory values of serum GPT were higher than those of serum GOT in all 17 patients. After tonsillectomy, the abnormal GOT levels in all patients gradually improved to the normal range before the 11th postoperative day and GPT levels did so before the 25th day. Measurement of intracellular transaminase activity of the palatine tonsil suggested that the migration of intracellular transaminase from tonsillar cells to serum would not elevate the serum transaminase level. Postoperative changes in serum transaminase and serum cholinesterase were different from the recovery process observed in fatty liver. The high transaminase level observed in patients with tonsillectomy is suspected to be due to other organs, rather than continuous inflammation of the palatine tonsil. PMID- 8366405 TI - [Prognostic factors in primary lymphoma of the thyroid--a review of 74 cases]. AB - Prognoses and prognostic factors in 74 patients with primary lymphoma of the thyroid gland were analyzed. From 1968 to 1991, 74 patients with non-Hodgkin's lymphoma originating in the thyroid gland were treated at Noguchi Thyroid Clinic Hospital. Patients consisted of 53 females and 21 males, with a median age of 64.5 years. Survival curves were calculated by the Kaplan-Meier method and significance was tested by generalized Wilcoxon test. The overall 5-year and 10 year survival rates were 81.8% and 62.5%, respectively. The survival rate in stage II disease was significantly (P = 0.004) lower than that in stage I. By the LSG classification, there was no significant difference in survival curves between follicular lymphoma and diffuse lymphoma. Using the Working Formulation, there was no significant difference in survival curves between cases with low and intermediate grade histology. Histologic subtype of the tumor did not appear to be a significant determinant of prognosis. Patients with vocal cord paralysis had poorer survival rates than others (P = 0.001). Extrathyroidal spread of the tumor by direct soft tissue invasion had a distinctly adverse effect on prognosis. PMID- 8366407 TI - [Clinical application of transiently evoked otoacoustic emissions in screening for auditory dysfunction]. AB - Transiently evoked otoacoustic emissions (TEOAE) should be used clinically as an objective and noninvasive screening test for auditory dysfunction in children. The features of TEOAE measured by "ILO88" with non linear click stimuli are discussed. The following results were obtained: 1) The normal range of a power spectrum was determined using 42 adults with normal hearing and compared with data for sensorineural hearing disturbance. The power spectrum of TEOAE in adults with normal hearing sloped downward at high frequency and was the same for right and left ears in both males and females. For comparison with sensorineural hearing disturbance, a significant correlation between the audiogram and power spectrum of TEOAE was sought. 2) Patients with otitis media with effusion (109 ears in 67 children) were examined by audiometry, tympanometry and TEOAE. The hearing disturbance threshold of 45 cases with TEOAE was lower than that in cases with no TEOAE. In tympanometry, low intratympanic pressure was noted in the absence of TEOAE. 3) TEOAE and spontaneous otoacoustic emission were examined in 42 adults with normal hearing and 27 neonates using the same probe and level of stimuli to clarify differences in TEOAE according to age. The amplitude of TEOAE and the highest peak of the frequency component at 4kHz in neonates exceeded those of adults. The peak stimuli recorded with the intracanal probe in neonates was also larger than that of adults. Three out of 15 neonates had spontaneous otoacoustic emission and essentially the same proportion was noted in young adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366406 TI - [Clinical studies on the furosemide VOR test]. AB - In order to detect vestibular endolymphatic hydrops, the directional preponderance of the VOR gain (VOR-DP%) during sinusoidal rotation (freq. 0.1Hz; Amp. 120deg) was calculated and compared between pre- and post-intravenous injections of furosemide (20mg). Abnormal changes in VOR-DP% (> = 10%) from the pre-injection level were referred to as positive in this furosemide VOR test (FVOR). The following results were obtained from this study. (1) Positive responses were obtained in 31 of 61 (51%) patients with definite Meniere's disease, in 11 of 21 (52%) patients with delayed endolymphatic hydrops and in 7 of 10 (70%) with syphilitic labyrinthitis. In contrast, the majority of patients responded negatively with sudden deafness or other peripheral vestibular disorders. (2) Following the endolymphatic shunt operation, in 2 out of 3 patients (67%) in whom vertiginous attacks had been decreased or disappeared after the operation results changed from positive to negative. (3) The positive rate in Meniere's disease was dependent on the frequency of the vertiginous attacks before the test or the duration from the last attack to the test. (4) Combined with the glycerol dehydration test or electrocochleography, the FVOR test could detect endolymphatic hydrops of Meniere's disease at a high positive rate. (5) There were no side-effects of the furosemide on the inner ear, such as deterioration of hearing acuity or tinnitus. In conclusion, the FVOR test is useful for detecting and following up fluctuating vestibular endolymphatic hydrops, which occur in disorders such as Meniere's disease, delayed endolymphatic hydrops and syphilitic labyrinthitis. PMID- 8366408 TI - [Clinical observation of acute otitis media in children]. AB - The efficacy of a combination of cefaclor and fosfomycin otic solution was investigated in 81 children with acute otitis media, who needed myringotomy for severe erythema and swelling of the tympanic membrane. The patients were followed up for one year to investigate correlations between test findings of early treatment and both clinical course and prognosis. These drugs were used for 10 days, and the effects of combined use were evaluated from findings in the tympanic membrane after the 10-day period. Three stages were assessed; cured, recovered and unchanged. In cured and recovered cases, the administration was evaluated to be effective. Within 2 weeks after the start of treatment, views of the ears, nose and epipharynx were roentgenographically examined for shadows of mastoid pneumatization and the paranasal sinuses, and the presence or absence of adenoid vegetation. After the antibiotic administration, the patients were instructed to visit us at least once every 3 months to rule out recurrence of acute otitis media and otitis media with effusion (possibly occurring one year after treatment). The following results were obtained. 1. The two drug combination was effective in 99% of patients, produced no side effects, and was deemed extremely useful. 2. The course of acute otitis media tended to be significantly prolonged in patients with mastoid pneumatization and paranasal sinus shadows as revealed by roentgenography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366409 TI - Histologic observations on the topography of a human periodontal pocket viewed in transverse step-serial sections. AB - A histologic overview of a periodontal pocket at the distal of a maxillary first premolar is presented. The material studied is part of the Bernhard Gottlieb collection. This material demonstrated the topography of the periodontal pocket through its complete circumference as seen in transverse step serial sections. From these observations, it is also clear that multiple pockets had formed, each involving a different area of the root surface. The pockets terminated independently and are separated from each other by areas of tissue which progress from pocket epithelium to junctional epithelium to connective tissue attachment. The existence of independent pockets around the root surface of a single tooth points to the problem of access and thus the predictability of non-surgical therapy as well as concerns that surgical access will necessarily involve areas of unaffected tissues. PMID- 8366410 TI - Current status of lasers in soft tissue dental surgery. AB - The aims of this paper are to briefly describe laser physics, the types of lasers currently available for use on soft tissues focusing primarily on CO2 and Nd:YAG laser energies, the histological effects of lasers on oral tissues, laser safety, the clinical applications of lasers on oral soft tissues, and future directions. Of the two types of lasers currently available for dental applications, both the CO2 and Nd:YAG lasers can be used for frenectomies, ablation of lesions, incisional and excisional biopsies, gingivectomies, gingivoplasties, soft tissue tuberosity reductions, operculum removal, coagulation of graft donor sites, and certain crown lengthening procedures. The advantages of lasers include a relatively bloodless surgical and post-surgical course, minimal swelling and scarring, coagulation, vaporization, and cutting, minimal or no suturing, reduction in surgical time, and, in a majority of cases, much less or no post surgical pain. CO2 lasers, compared to Nd:YAG are faster for most procedures, with less depth of tissue penetration and a well-documented history. There have been recent reports on the use of the Nd:YAG laser for periodontal scaling, gingival curettage, and root desensitization, but further research needs to be conducted. Both the CO2 and the Nd:YAG laser have limited use in conventional flap therapy. PMID- 8366411 TI - Effects of antibiotic treatment on clinical conditions and bacterial growth with guided tissue regeneration. AB - Mucogingival flaps were reflected over pairs of mandibular molar teeth with Class II furcation invasions. The dimensions of the furcations were measured. The teeth were debrided and an expanded polytetrafluoroethylene (e-PTFE) membrane was placed and retained over one furcation of each pair (test site) for 4 weeks. The second site served as a control. Eight patients (group 1) with 12 e-PTFE sites received no antibiotic. Seven patients (group 2) with 12 e-PTFE sites were administered amoxicillin/clavulanate potassium for 10 days. Paper-points were used to collect bacterial samples and clinical indices were recorded at baseline and weekly for 4 weeks. Paper-point samples and the e-PTFE collected at week 4 were sonicated and analyzed by DNA probes for seven putative pathogens. At baseline no parameter showed statistical differences between groups or sites. At week 1 significantly greater levels of Prevotella intermedia type I (P < 0.05) and Fusobacterium nucleatum (P < 0.01) were found in group 1. At week 4, paper point samples from test sites (P < 0.05) and e-PTFE materials (P < 0.001) showed significantly higher presence of Bacteroides forsythus in group 1. No significant microbial changes were found for control sites over time or between groups. The total bacterial load at test sites over time increased similarly for patients administered or not administered the antibiotic. Clinical signs of inflammation were significantly greater in group 1 and associated with the presence of B. forsythus (P < 0.01). PMID- 8366412 TI - Collagen membrane barrier therapy to guide regeneration in Class II furcations in humans. AB - This study was undertaken to evaluate the effectiveness of resorbable collagen membranes in guided tissue regeneration. The study participants were 38 adults with moderate to advanced periodontitis. Each patient had at least one Class II furcation defect which could serve as either a test or control tooth. The cases were randomized prior to selection, so that investigators did not known whether the patient would be a test case or a control case until the time of surgery. Sites were surgically exposed and measurements were recorded from the cemento enamel junction (CEJ) directly coronal to the furcation area to the alveolar crest, and to the base of the defect. Horizontal furcation measurements were also made, using a color coded furcation probe. The test patients had a trimmed and shaped collagen membrane barrier placed over the prepared furcation area. The control patients received the identical surgical management, except that no collagen membrane barrier was placed. All patients received normal post-surgical care, and at 12 weeks post-surgery, were scheduled for re-entry surgery. The re entry mucoperiosteal flaps were designed to expose the furcation area for measurements, as described above. There was clinical improvement in all measurements made in both the test and control patients over the 3-month period. The horizontal furcation measurement and the CEJ to base of alveolar defect measurements did yield a statistically significant improvement when comparing the test patients to the controls. PMID- 8366413 TI - Pain and discomfort levels in patients during root surface debridement with sonic metal or plastic inserts. AB - The study was designed to evaluate whether root surface debridement with a sonic scaler plastic insert would cause less pain and discomfort to patients than an ordinary, probe-shaped metal sonic insert. One quadrant in each of 23 patients was debrided with each insert. Blood pressure, mean arterial pressure, and heart rate were monitored before, during, and immediately after each treatment. Pain was also evaluated on a visual analogue scale (VAS) after each treatment, as well as 2 weeks later following pain-provoking stimuli. Blood pressure, mean arterial pressure, and heart rate did not reveal any differences between quadrants treated with plastic or metal inserts. Heart rate had a weak, positive association with treatment time. The VAS gave a higher pain score for the plastic (30.8) than for the metal insert (24.4), but this difference was not statistically significant (P = 0.055). Following pain-provoking stimuli at the 2-week follow-up visit, quadrants debrided with the metal insert (31.3) scored significantly lower (less pain) (P < 0.01) on the VAS than quadrants treated with the plastic insert (30.7). It is concluded that the sonic metal insert caused less pain and discomfort to the patients due to its superior accessibility and water spray cooling. The significant difference between metal and plastic tip debrided quadrants at the follow-up visit was probably caused by the smearing effect of the metal insert with partial closure of the dentin tubule orifices. PMID- 8366414 TI - Progression of periodontal disease in HIV seropositive patients. AB - Data from cross-sectional studies suggest that periodontitis in HIV-infected patients is a more destructive form of disease in contrast to the slowly progressing form of adult periodontitis in the general population. We studied prospectively over an 18-month period 30 HIV infected, but asymptomatic, patients and compared the rate of periodontal attachment loss with that of a healthy control group (n = 10) matched for age and plaque index. Every 6 months, each subject was assessed for their clinical status by a physician and CD4+ cell count determined. The proliferative response of peripheral blood lymphocytes was determined by in vitro cultures with PHA and Con A. The periodontal health status was assessed by scoring with plaque index (PI), gingival index (GI), and periodontal disease index (PDI). The control subjects were assessed for periodontal status only. Of the 30 HIV-positive patients whose data were analyzed 14 received Zidovudine (AZT) while the remaining 16 did not. There was no correlation between any clinical parameter measured and periodontal status as determined by PI or GI. However, a significant difference in the change of periodontal disease index (PDI) was observed between the HIV-infected and control groups (P = 0.005). We concluded that HIV-infected patients with pre-existing periodontitis tend to experience a greater rate of attachment loss over time compared with controls. PMID- 8366415 TI - The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro. AB - The ability of fibroblasts to reproduce and attach to teeth is of paramount importance in re-establishing the lost connective tissue attachment after periodontal therapy. This study examined the effect of nicotine, a major component of the particulate phase of tobacco smoke, on human gingival fibroblast (HGF) reproduction and attachment to tissue culture surfaces. Pooled HGF cultures made from explants of gingival biopsies were utilized between passages 5 and 10 and plated in 96-well plates at 1.0 x 10(4) cells per well. Cell numbers were determined using 3-(4,5-dimethylthiazol-2-y)-2,5-diphenyl tetrazolium bromide (MTT), which is a reflection of mitochondrial dehydrogenase activity. The concentrations of nicotine used were 0.025, 0.05, 0.1, 0.2, and 0.4 microM, the average serum concentration for a smoker being approximately 0.1 microM. The effect of continuous nicotine exposure on HGF reproduction was determined by incubating cell cultures and media containing nicotine for up to 48 hours. Residual toxicity was determined by preincubating cells with nicotine for 1 or 6 hours. HGF suspensions and increasing concentrations of nicotine were added together to determine the effect on attachment. Results showed an enhanced effect of nicotine on HGF attachment, with increasing numbers of cells attaching with increasing nicotine concentrations, compared to the control. Low concentrations of nicotine had a stimulatory effect on cell replication, while higher concentrations of nicotine appear to have no significant effect on HGF reproduction. The responses of cells to some concentrations of nicotine may persist after its removal. PMID- 8366416 TI - Gingival crevicular blood for assessment of blood glucose in diabetic patients. AB - In this study 50 patients with diabetes mellitus had gingival crevicular blood from periodontal probing collected in small plastic pipettes. The pipettes transferred the crevicular blood to a non-wipe glucose self-monitoring instrument. At the same time, finger-stick capillary blood measurements were analyzed in the same glucose self-monitoring instrument, and venous blood was collected for measurement in a laboratory glucose analyzer. Each laboratory measurement was corrected from a serum glucose value to a whole blood glucose value by a function of the patient's hematocrit. This corrected glucose value allowed direct comparison of the laboratory measurement to the intraoral and finger-stick whole blood measurements. The patient blood glucose concentrations ranged from 59 mg/dl to 366 mg/dl. The gingival crevicular blood exhibited a correlation of r = 0.975 (P < .0001) to the corrected laboratory standard measurement, with a mean prediction error (bias) of -4.11 mg/dl and a root mean square error (precision) of 17.43 mg/dl. The finger-stick blood had a correlation of r = 0.983 (P < .0001) to the corrected laboratory standard, with a mean prediction error of 4.65 mg/dl and a root mean square error of 14.48 mg/dl. The American Diabetic Association recommends that the prediction error of blood glucose monitoring devices fall within 15% of the laboratory standard. Using this criterion 92% of the gingival crevicular measurements and 90% of the finger puncture measurements fell within 15% of the laboratory value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366417 TI - Oral-dental findings in a case of Maffucci's syndrome. AB - A case of Maffucci's syndrome (MS) in a 17-year-old Caucasian female is presented with a thorough intraoral examination. The prominent finding was recurrent gingival hyperplasia affecting both the free and attached gingiva with deep periodontal pockets, tooth mobility, pathological tooth migration, and severe alveolar bone loss. Furthermore, the pattern of alveolar bone destruction, in many ways, resembled that of localized juvenile periodontitis. Although there is always the possibility that these oral features may not be related with the syndrome, we suggest a careful dental and periodontal examination in future cases, which we believe will help develop a better description of oral findings in MS. PMID- 8366418 TI - You can't not believe everything you read. AB - Can people comprehend assertions without believing them? Descartes (1644/1984) suggested that people can and should, whereas Spinoza (1677/1982) suggested that people should but cannot. Three experiments support the hypothesis that comprehension includes an initial belief in the information comprehended. Ss were exposed to false information about a criminal defendant (Experiments 1 and 2) or a college student (Experiment 3). Some Ss were exposed to this information while under load (Experiments 1 and 2) or time pressure (Experiment 3). Ss made judgments about the target (sentencing decisions or liking judgments). Both load and time pressure caused Ss to believe the false information and to use it in making consequential decisions about the target. In Spinozan terms, both manipulations prevented Ss from "unbelieving" the false information they automatically believed during comprehension. PMID- 8366419 TI - Unemployment, distress, and coping: a panel study of autoworkers. AB - This study of coping with unemployment traces the distress levels of workers in 4 closing and 12 nonclosing General Motors (GM) plants. Workers were interviewed 3 months before plants closed, 1 year after, and 2 years after (final N = 1,136). Tested were (a) effects of unemployment on symptoms of depression, anxiety, and somatization; (b) linkages between depression and subsequent unemployment, controlling for workers' gender, race, marital status, age, education, prior income, and seniority; and (c) the relationship between workers' coping decisions and subsequent depression. Results showed that unemployment at Waves 2 and 3 was related to prior frequency of symptoms of depression. Depression, in turn, was alleviated for workers whose coping decisions at Wave 2 fit with their Wave 3 outcomes: those who both wanted and found a job, lost a job they disliked, or remained unemployed as planned. PMID- 8366420 TI - Motivated augmentation and reduction of the overattribution bias. AB - Three experiments investigated whether the need to have (or avoid) cognitive closure affects observers' tendency to display attributional bias. Results of each experiment indicate that the overattribution bias was magnified under high need for cognitive closure and attenuated under high need to avoid closure. In Experiments 1 and 3, the relevant motivational state was manipulated situationally, whereas in Experiment 2 an individual-differences measure of the closure motivation was used. These divergent operationalizations yielded convergent results. Furthermore, when in Experiment 3 the task consisted of attributions to the situation, high need for closure augmented, and high need to avoid closure reduced, situational rather than dispositional overattributions. The results imply general motivational boundary conditions for inferential biases across judgmental contents. PMID- 8366421 TI - Adaptive significance of female physical attractiveness: role of waist-to-hip ratio. AB - Evidence is presented showing that body fat distribution as measured by waist-to hip ratio (WHR) is correlated with youthfulness, reproductive endocrinologic status, and long-term health risk in women. Three studies show that men judge women with low WHR as attractive. Study 1 documents that minor changes in WHRs of Miss America winners and Playboy playmates have occurred over the past 30-60 years. Study 2 shows that college-age men find female figures with low WHR more attractive, healthier, and of greater reproductive value than figures with a higher WHR. In Study 3, 25- to 85-year-old men were found to prefer female figures with lower WHR and assign them higher ratings of attractiveness and reproductive potential. It is suggested that WHR represents an important bodily feature associated with physical attractiveness as well as with health and reproductive potential. A hypothesis is proposed to explain how WHR influences female attractiveness and its role in mate selection. PMID- 8366422 TI - Household crowding and social support: a quasiexperimental analysis. AB - People often cope with crowded living conditions by socially withdrawing from their housemates. This coping strategy may overgeneralize, influencing social interactions with others outside the home. In a stressful laboratory situation, Ss from crowded homes, in comparison with uncrowded counterparts, are less likely to seek support from a confederate and rate the confederate as less supportive. Moreover, Ss from crowded homes are less likely to offer support to a confederate in need. These differences in social interaction behaviors appear to be attributable to crowded residents' social withdrawal. PMID- 8366423 TI - Self-perpetuating properties of dysphoric rumination. AB - Hypotheses about the self-perpetuating properties of ruminative responses to depressed mood were tested in 2 laboratory studies and 2 questionnaire studies with dysphoric and nondysphoric Ss. Studies 1 and 2 supported the hypothesis that dysphorics induced to engage in self-focused rumination would report reduced willingness to engage in pleasant, distracting activities that could lift their moods, even if they believed they would enjoy such activities. Studies 3 and 4 confirmed the hypothesis that dysphorics induced to ruminate in response to their moods would feel they were gaining insight into their problems and their emotions. Therefore, they might have avoided distraction because they believed it would interfere with their efforts to understand themselves. Depressed mood alone, in the absence of rumination, was not associated with either lower willingness to participate in distractions or an enhanced sense of insightfulness. PMID- 8366424 TI - Social support and undermining in close relationships: their independent effects on the mental health of unemployed persons. AB - Structural equation analyses were used to examine the impact of social support vs. social undermining (conflict) on mental health in longitudinal data from 1,087 recently unemployed respondents. The results demonstrated that social support and social undermining were not the opposite poles of the same factor, each having some impact independent of the other. Social undermining had statistically significant and strong adverse impact at each concurrent level of mental health. It also predicted improvement (but not a high level) in mental health in subsequent time waves. In contrast, social support had a significant beneficial impact on mental health only at Time 1. Compared with the volatile and extreme effects of social undermining, those of social support appear weaker but more stable. These findings are consistent with literature on the impact of life events (S. E. Taylor, 1991) and on marital interactions and satisfaction (J. M. Gottman & L. J. Krokoff, 1989). PMID- 8366425 TI - Competence, delinquency, and attempts to attain possible selves. AB - The impact of impulsivity, possible selves, and social and communication skills on delinquent involvement in inner-city high school and incarcerated boys (aged 13-17, N = 230) was explored. Impulsivity, perceived attempts to attain possible selves, and balance in possible selves were hypothesized to directly influence delinquency. Social and communication skills were hypothesized to influence delinquency directly and indirectly through their effects on impulsivity, balance, and attempts to attain possible selves. These factors discriminated moderately well between high school and incarcerated youths. Impulsivity was an especially powerful predictor of self-reported delinquency among high school youths but not among incarcerated youths. The effect of other variables differed somewhat for different categories of delinquency (aggression, theft, hooliganism, and school truancy) and between subsamples, suggesting the importance of examining the subjective meaning of each of these behaviors for the individual in his social context. PMID- 8366426 TI - How coping mediates the effect of optimism on distress: a study of women with early stage breast cancer. AB - At diagnosis, 59 breast cancer patients reported on their overall optimism about life; 1 day presurgery, 10 days postsurgery, and at 3-, 6-, and 12-month follow ups, they reported their recent coping responses and distress levels. Optimism related inversely to distress at each point, even controlling for prior distress. Acceptance, positive reframing, and use of religion were the most common coping reactions; denial and behavioral disengagement were the least common reactions. Acceptance and the use of humor prospectively predicted lower distress; denial and disengagement predicted more distress. Path analyses suggested that several coping reactions played mediating roles in the effect of optimism on distress. Discussion centers on the role of various coping reactions in the process of adjustment, the mechanisms by which dispositional optimism versus pessimism appears to operate, third variable issues, and applied implications. PMID- 8366427 TI - A dark side of the American dream: correlates of financial success as a central life aspiration. AB - Aspiring for financial success is an important aspect of capitalist cultures. Three studies examine the hypothesis that values and expectancies for wealth and money are negatively associated with adjustment and well-being when they are more central to an individual than other self-relevant values and expectancies. Studies 1 and 2 use 2 methods to show that the relative centrality of money related values and expectancies is negatively related to college students' well being and mental health. Study 3, using a heterogeneous noncollege sample, extends these findings by showing that a high centrality of aspirations for financial success is associated with interview ratings of lower global adjustment and social productivity and more behavioral disorders. Discussion is focused on the deleterious consequences of materialistic world views and the need to examine differential effects of content regarding goals and values. PMID- 8366428 TI - [Membrane-bound proteases involved in neuropeptide degradation in the brain]. AB - The action of neuropeptides at the synapse is terminated through enzymatic degradation by membrane-bound proteases. We defined and purified membrane-bound proteases functioning at the initial stage of degradation of four neuropeptides. 1. Substance P-degrading endopeptidases isolated from the rat brain and pig striatum showed similar properties to those of endopeptidase-24.16 (neurolysin) except for cleavage sites of substance P. 2. LHRH fragment (1-5)-generating endopeptidases isolated from the neuroblastoma cells and rat brain showed similar properties to those of endopeptidase-24.15 (thimet oligopeptidase). 3. One of two dynorphin-degrading cysteine proteases isolated from neuroblastoma cells showed strict specificity toward the Arg-Arg residues. 4. Endopeptidase-24.11 (neprilysin) isolated from the rat brain was identified as a somatostatin degrading enzyme. PMID- 8366429 TI - [Stability of allantoin and identification of its degradation compounds]. AB - The stability of allantoin was studied in pH 3.0, 6.0, and 8.0 buffer solutions at 50 degrees C for 55 d. Allantoin was determined by high performance liquid chromatography (HPLC) with a cation exchange mode and colorimetry. The known degradation compounds, allantoic acid and glyoxylic acid, were simultaneously determined by ion chromatography. Urea was determined by HPLC with an ion pair mode. In the stability studies on pH 6.0 and 8.0 solutions, new degradation compounds of allantoin were identified as two growing unknown peaks in the HPLC chromatogram. Isolation of these compounds by preparative HPLC and 1H, 15N and 13C-NMR spectra revealed that they were condensates of allantoin and glyoxylic acid, which also reacted positively in phenylhydrazine colorimetry. The amounts of these compounds were calculated from the determination results of other allantoin related compounds in the buffer solutions and were estimated as the biggest amount among all other compound. As they were found to be stable in an alkaline solution, conditions for hydrolysis in the colorimetric determination of allantoin were further examined. It was found that the longer hydrolysis gave more than 90% recovery in the colorimetry. PMID- 8366430 TI - [Effects of selenium on the glycolysis and gluconeogenesis system in rat liver]. AB - We studied the effect of selenium on the glycolysis and gluconeogenesis system in the rat liver. Significant decreases in glucose level in the serum were observed from the 4th day after daily intraperitoneal (i.p.) administration of selenite (173 micrograms/kg, 78.9 micrograms/kg of selenium base equivalent). Selenium was also effective in reducing a precursor of gluconeogenesis, lactate, alanine or glycerol, in the serum. Moreover, there were significant decreases in the activities of pyruvate carboxylase and glucose-6-phosphatase, a rate-limiting enzyme of gluconeogenesis, in the liver of selenium-treated rates. On the contrary, the activities of glycokinase and phosphofructokinase, a rate-limiting enzyme of glycolysis, in the liver of rat treated with selenium significantly increased in comparison with the control group. These data, therefore, indicated that the hypoglycemic effect of selenium might be due to the acceleration of glucose metabolism and the inhibition of glucose synthesis in the liver, suggesting a decrease in a source of precursor supply for the gluconeogenesis. PMID- 8366431 TI - Gait style as an etiology to chronic postural pain. Part I. Functional hallux limitus. AB - A common, but locally asymptomatic and therefore rarely recognized functional inability of the first metatarsophalangeal joint to dorsiflex strictly during gait is described. Normal motion is present in this joint during nonweight bearing examination; therefore this is referred to as functional hallux limitus. Since this joint forms the pivot about which the entire body advances during each step, this disturbance in function, when repeated thousands of times on a daily basis, can alter foot and postural biomechanics. It can cause and perpetuate many chronic postural ailments, including lower back pain. When functional hallux limitus is specifically addressed in an orthotic treatment plan, 77% of long-term chronic postural pain patients exhibit 50% to 100% improvement in their overall condition, in spite of failing previous therapy on their specific site of pain and never exhibiting any foot symptomatology. PMID- 8366432 TI - Acute radiodermatitis following radiotherapy for classic Kaposi's sarcoma. AB - There is a high incidence of radiation toxicity associated with Kaposi's sarcoma. The authors review acute radiodermatitis and present a case where it occurred in the foot following radiotherapy for classic Kaposi's sarcoma. PMID- 8366433 TI - Effect of extrinsic rearfoot posts on rearfoot position. AB - Twenty runners displaying abnormal subtalar joint pronation were selected for this study, the purpose of which was to investigate the effects of extrinsic rearfoot posted orthoses on frontal plane rearfoot and tibial position. Numerous temporal events were measured and compared for three different conditions: acrylic post, Birko post, and no post. The results suggested that rearfoot posts have a somewhat limited function in foot orthotic therapy and that the choice of posting material is of limited functional value. PMID- 8366434 TI - Polyunsaturated fatty acid supplementation in peripheral neuropathy. AB - This study is an attempt to assess the role of dietary supplementation in the treatment and prevention of diabetic peripheral neuropathy. The authors developed an animal model system to study this problem. Animals given streptozotocin to induce a type I diabetic state showed elevated glucose levels and decreased body weight. Analysis of the sciatic nerve revealed a decrease in nerve conduction velocity and Na(+)-K(+)-ATPase activity. The activity of protein kinase C, another component of the nerve transmission process, was also affected by the diabetic state. The dietary intervention of polyunsaturated fatty acids seemed to revert some of these changes toward normal. PMID- 8366435 TI - Epidermal culture and grafting. A brief review. AB - In summary, technological advances in culturing epidermis for the purpose of grafting allow this approach in the treatment of cutaneous wounds. Certainly, full- and split-thickness autografts offer immediate availability and permanent wound coverage, but they also involve a large, painful donor site. Cultured epidermal autografts can provide permanent wound coverage, but the delay required for cultivation of confluent sheets of keratinocytes makes them somewhat less desirable. Both allografts and cultured allografts, on the other hand, are available for immediate use, but the possibility of infectious disease transmission may be a concern. In any case, all types of skin grafts function as biological dressings that promote the proliferation of the host's epidermis and, thus, facilitate the ability of the patient's skin to repair itself. PMID- 8366436 TI - Arthrodesis of the navicular medial cuneiform joint. A case report. PMID- 8366437 TI - Subcutaneous alternariosis of the foot in a patient on corticosteroids. AB - To the authors' knowledge, this is the first reported case of alternariosis involving the subcutaneous tissues of the foot. Podiatrists are likely to see more of this condition and other unusual fungi causing deep foot infections in the future because of the increasing population of immunocompromised patients. PMID- 8366438 TI - Foot problems in the US. The 1990 National Health Interview Survey. PMID- 8366439 TI - Iatrogenically induced Charcot foot. PMID- 8366440 TI - Meeting the challenge of the 1990s: strategies to provide quality perinatal services in an era of decreasing reimbursement. PMID- 8366441 TI - Hospital policies as they affect quality in the 1990s: a case for change? PMID- 8366443 TI - Patient satisfaction: an outcome measure for maternity services. PMID- 8366442 TI - Linking perinatal standards, documentation, and quality monitoring. PMID- 8366444 TI - Developing a CareMap for patients with a cesarean birth: a multidisciplinary process. PMID- 8366445 TI - Nurse-midwives and the peer review process. PMID- 8366446 TI - Implementing a neonatal resuscitation quality improvement committee. PMID- 8366447 TI - Linking neonatal documentation with standards of care and quality improvement. PMID- 8366448 TI - Facilitating parental involvement through documentation. PMID- 8366449 TI - Cast titanium implants for localized ridge defects: a clinical report. AB - A technique that allows the correction of alveolar ridge defects with titanium implants and pin stabilization is described. The use of titanium pins has improved the intimacy of contact of the implant with the bone, which simplifies implant placement and enhances implant stabilization. PMID- 8366450 TI - Apparent intrusion of natural teeth under an implant supported prosthesis: a clinical report. PMID- 8366451 TI - Periodontal and prosthodontic treatment of amelogenesis imperfecta: a clinical report. PMID- 8366452 TI - Clinical success of cast metal posts and cores. AB - The topic of posts for endodontically treated teeth has received considerable attention in the literature, but there is sparse in vivo research and certain information from in vitro investigations is contradictory. A retrospective study of 1273 endodontically treated teeth in the practices of nine dentists in general practice indicated an inordinately high failure rate with cast posts and cores compared with alternate systems of coronoradicular stabilization. However, a closer evaluation of the data in this study indicated that almost half of the cast posts were half the desired length or less. The indications for the cast post and core are discussed and the specific causes of failure are reviewed. Additional research is needed to compare the success rate of securely seated cast posts and cores with alternate methods of coronoradicular stabilization. PMID- 8366453 TI - Effect of bone mineral density in skeleton and mandible on extraction of teeth and clinical alveolar height. AB - Residual ridge resorption of the maxillae and mandible after tooth extraction adversely affects many edentulous people. The jaws of 355 postmenopausal women were examined clinically, and the number of teeth and the clinical height of alveolar ridges in edentulous jaws were determined. Each subject was asked when the last teeth had been extracted. To study the bone mineral status of each woman, the bone mineral densities of the femoral neck and the lumbar spine were measured by dual-energy x-ray absorptiometry. For 77 edentulous or almost edentulous women, the bone mineral density of the mandibular cortex and the spongiosa were measured by quantitative computed tomography. The results were studied to determine whether the general status of osteoporosis or the local bone mineral densities in the mandible affect the time of extraction of teeth or the remaining height of edentulous alveolar ridges. Neither the time when the teeth were lost nor the number of teeth was dependent on the general bone loss, but in some regions, the clinical height was affected. PMID- 8366454 TI - Some physical properties of an improved facial elastomer: a comparative study. AB - An attempt was made to evaluate some properties of clinical importance of a new facial elastomer, Cosmesil HC2. A comparative study versus Silskin II and Cosmesil SM4 was also carried out and took into account the effect of weathering after exposure to ultraviolet radiation. The results showed that Cosmesil HC2 is a resilient material and yet displays good tensile characteristics. The results also showed that weathering does not significantly affect Cosmesil HC2 elastomer's tear strength. The overall effect of irradiation was moderate in all materials tested. PMID- 8366455 TI - Isokinetic exercise management of temporomandibular joint clicking in young adults. AB - Temporomandibular joint clicking is frequently a sign of craniomandibular disorders, and the etiologic predisposing, initiating, and perpetuating factors must be considered in its management. The present study assesses the usefulness of isokinetic exercises in the treatment of temporomandibular joint clicking. At the end of a 6-month test period, 18 of 22 subjects (approximately 82%) with clicks no longer had clicking, but four subjects (approximately 18%) with bilateral reciprocal clicking did not lose their clicks. A number of proposals have been suggested in the past as an explanation of the cause of temporomandibular joint clicking, but the present study has shown that clicking in young adults is predominantly neuromuscular in origin and may be a reversible condition that can be treated successfully with a conservative exercise regimen. PMID- 8366456 TI - Comparison of muscle activity between conventional and neuromuscular splints. AB - The muscle relaxation appliance (MRA) has been used in the treatment of myofascial pain dysfunction (MPD) patients. The neuromuscular orthotic is a version of the MRA and is constructed from a three-dimensional mandibular position when muscles are in a state of minimal electromyographic (EMG) activity. The purpose of this study was to investigate the affect of two muscle relaxation appliances and a placebo (cotton rolls) on EMG activity of the functional masseter and anterior temporalis muscles. A centric relation mandibular MRA and a neuromuscular orthotic were constructed under controlled protocols for 12 women MPD patients with a mean age of 38 years. EMG measurements were taken during a 10 second clench of both appliance and placebo. No statistical difference was found between the centric relation mandibular MRA and neuromuscular orthotic. A statistically significant difference was found between the mean EMG values of the placebo and two treatment appliances. PMID- 8366457 TI - Transmandibular implant system for the atrophic mandible: a case report of its use in the partially dentate mandible. PMID- 8366458 TI - Annual review of selected dental literature: report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry. AB - The annual review of selected dental literature this year cites 384 published papers and reports. This year's review contains more editorial comment than reviews of years passed. New data on the biological responses to materials is emphasized in several sections. Observations on new compounds able to prevent plaque formation are presented. Clinically relevant advances in knowledge concerning the etching of different tooth structures are reported along with the effect of etching procedures on the dental pulp. Evaluation of periodontal diseases in all age groups is a topic. Limitations of current diagnostic techniques in periodontal disease, temporomandibular disorders, and implant therapy are included. There are new views on the use of dental amalgam. The future use of dental mercury is predicted. Interest in new ceramic systems is indicated as the demand for esthetics continues. Clinical information is emphasized over scientific information throughout this year's review. PMID- 8366459 TI - Bond strength of composite resin to porcelain with newer generation porcelain repair systems. AB - A laboratory study was conducted to evaluate the mean shear bond strength of composite resin bonded to porcelain with the use of eight newer generation repair systems. The range of shear bond strength after 24 hours of water storage was 23.5 +/- 5.3 MPa to 12.0 +/- 2.3 MPa. After 3 months of water storage and thermocycling, the bond strength range was 20.7 +/- 1.7 MPa to 4.2 +/- 1.0 MPa. Three of eight systems evaluated did not exhibit a significant (p > 0.05) decrease in bond strength when the 24-hour bond strengths were compared with the 3-month bond strengths. Most specimens failed cohesively in the porcelain at 24 hours, but at 3 months only four of the eight systems showed consistent failures in the porcelain. PMID- 8366461 TI - Flexural strength of provisional restorative materials. AB - A provisional restorative material must be strong enough to resist fracture during function. This study tested five autopolymerizing provisional resin materials under conditions that related the stresses acting on them to those acting on a fixed partial denture. The highest values for fracture resistance were displayed by Snap poly(ethyl methacrylate) material. However, two of the 11 samples of this material displayed markedly lower values for fracture resistance. This finding warrants further investigation, because inconsistency had clinical implications. In decreasing order, the fracture resistance of the other materials was as follows: the poly(methyl methacrylate) materials, Caulk temporary bridge resin and G-C Unifast temporary resin; the composite material, Protemp; and the epimine material, Scutan. PMID- 8366460 TI - The relationship of the incisive papilla to the maxillary central incisors and canine teeth in southern Chinese. AB - A photographic technique was used to measure anatomic landmarks located on dental casts. The relationship of the maxillary anterior teeth to the incisive papilla in a Southern Chinese population living in Hong Kong was studied. The distances from the labial surface of the central incisors to the midpoint and the posterior border of the incisive papilla were measured. The area on the incisive papilla where the intercanine line crossed was noted. The data obtained were compared with those from previous studies of Caucasians. Results show that there is little difference between the Southern Chinese in this study and most other ethnic groups. The guidelines that use the incisive papilla as a reference for the setting of artificial teeth in denture construction recommended for Caucasians can be applied to Southern Chinese patients. PMID- 8366462 TI - Placement of retraction cord during porcelain laminate (veneer) restorative procedures. PMID- 8366463 TI - A way to quantify the occlusal factors of excursive movements. PMID- 8366464 TI - The relationship of depression to dissociation in patients with bulimia nervosa. AB - Dissociative Experiences Survey scores were compared between bulimics with and without depression, and among depressed patients with and without bulimia. An association is noted between depression and dissociation, confounding the previously noted relationship between bulimia nervosa and dissociation. PMID- 8366465 TI - An MCMI cluster typology of obsessive-compulsives: a measure of personality characteristics and its relationship to treatment participation, compliance and outcome in behavior therapy. AB - The two-fold purpose of this investigation was to (a) define personality subtypes among patients diagnosed with obsessive-compulsive disorder (OCD) and (b) examine the relationship between the resulting typology and treatment participation, compliance and outcome of OCD patients treated with behavior therapy, using exposure and response prevention. A hierarchical agglomerative cluster analysis was performed on the Millon Clinical Multiaxial Inventory (MCMI) scale scores of 137 OCD patients seeking outpatient treatment; four cluster types emerged. Patients' OCD symptom severity was assessed at pretreatment, posttreatment, and 6 month follow-up using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Patients with no evident personality pathology and those with dependent qualities demonstrated the best overall outcome. Patients whose personalities indicated particular difficulties with interpersonal interaction were most likely to refuse behavior therapy and, among these patients who engaged in treatment, evidenced no reduction in OCD symptoms at posttreatment and follow-up. Patients with histrionic/borderline traits showed symptom reductions at posttreatment, but did not maintain their treatment gains at follow-up. The clinical implications of these findings are discussed. PMID- 8366466 TI - Effects of haloperidol on human plasma magnesium. AB - The effect of haloperidol treatment on human plasma levels of magnesium (Mg), calcium (Ca) and phosphorus (P) was assessed. Haloperidol treatment significantly reduced plasma Mg but not plasma Ca or P levels. This finding contrasts with studies using other neuroleptics where reductions in both Mg and Ca concentrations were observed. The addition of lithium to haloperidol treatment resulted in an elevation of plasma Mg, but not Ca or P, to levels significantly greater than those at baseline. The reduction of Mg levels by haloperidol may reflect the ion's involvement in the pathology of psychosis and/or in the mechanism of generating extrapyramidal side effects. PMID- 8366467 TI - Migraine headaches and psychopathology: future directions. PMID- 8366468 TI - Headache and personality: results of a community sample of young adults. AB - The present study investigated the association between personality, symptoms and headache subtypes in a prospective longitudinal epidemiologic study of a cohort of 19- and 20-year-olds in Zurich, Switzerland. Personality was assessed by the Freiburg Personality Inventory (FPI), a standardized self-report personality instrument, which yields nine primary factors and three secondary factors. The Symptom Checklist 90 (SCL-90) was employed to examine somatic and psychological symptoms. Subjects with migraine exhibited elevated rates of neuroticism compared to non-migraine subjects on FPI. Somatization was the only primary symptom factor on the SCL-90 which discriminated between subjects with migraine and those without migraine. Persons with migraine with aura exhibited greater impairment than any of the other headache subtypes or controls on both the FPI and SCL-90. Subjects with tension-type headache did not differ from controls on any of the personality or symptom factors. PMID- 8366469 TI - Headache syndromes and psychiatric disorders: association and familial transmission. AB - This paper examines the association between psychiatric disorders and headache syndromes in a longitudinal epidemiologic sample of young adults who were selected from the general population of Zurich, Switzerland. Headache syndromes were defined according to the newly introduced diagnostic criteria of the International Headache Society in 1988. The prevalence rates of psychiatric disorders, according to specific headache subtypes, were examined both cross sectionally and longitudinally. In the cross-sectional data, migraine with aura was associated with hypomania, recurrent brief depression, and all of the anxiety disorders, whereas only the phobic disorders and panic were elevated among subjects with migraine without aura. Similar findings emerged for the longitudinal data, with the exception that major depression was associated with both subtypes of migraine. Subjects with tension-type headaches did not differ from controls with respect to any of the effective or anxiety disorders in both the cross-sectional and longitudinal data. Prospective study data indicated that the age of onset of anxiety disorders generally preceded that of migraine and that the onset of affective disorders in the majority of comorbid subjects followed that of the onset of migraine. In order to investigate the mechanism for the associations between anxiety/depression syndromes and migraine, patterns of co-transmission of migraine and anxiety/depression were examined in data from a controlled family history study of migraine. The results were consistent with a syndromic relationship between migraine and anxiety/depression, rather than their representing discrete manifestations of shared underlying etiology. The implications of these data for research and clinical work are discussed. PMID- 8366470 TI - Migraine, physical health and psychiatric disorder: a prospective epidemiologic study in young adults. AB - In a prospective study of a random sample of 1,007 young adults, we examined the association between migraine and psychiatric disorder, physical complaints, indicators of functional impairment, and use of mental health services. A history of migraine was associated with increased lifetime rates of major depression, anxiety disorders, illicit drug use disorders, nicotine dependence, and suicide attempts. Compared with subjects without a history of migraine, those with such a history had significantly more physical symptoms and were more likely to report job absenteeism, assess their general health as fair or poor, and use mental health services. Follow-up data, gathered 14 months after the baseline interview, revealed that subjects with a history of migraine at the baseline had significantly increased rates of first incidence major depression and panic disorder during the interval period (odds ratio (OR) for major depression = 4.2, 95% confidence interval (CI) 2.0-9.2; and OR for panic disorder = 12.8, 95% CI 4.1-39.8). The risk for these psychiatric disorders in persons with prior history of migraine was unrelated to the recentness of their migraine attacks. These findings suggest that the link between migraine, major depression and anxiety might reflect a common predisposition. PMID- 8366471 TI - Migraine and depression: biological aspects. AB - There is a considerable overlap in migraine and depression incidence, and both conditions may be associated with low levels of 5-hydroxytryptamine (5-HT). During a migraine attack there is evidence for low levels of platelet 5-HT and possibly also low Vmax for 5-HT uptake; both these findings are also associated with the depressed state. Both conditions can be treated by tricyclic and monoamine oxidase inhibiting antidepressants. However, there are also clear differences: migraine attacks are brief and self limiting. Part of the migraine cascade occurs outside the blood brain barrier, presumably involving blood vessels and, unlike depression, migraine attacks can be ameliorated by drugs which only act peripherally. In addition, migraine patients, especially males, often have permanently low levels of platelet monoamine oxidase activity, whereas patients with unipolar depression tend to have raised levels of this marker. This low enzyme activity may reflect part of the vulnerability to migraine, often associated in the prodromal phase with agitation or hyperactivity. Migraine may form part of a family of brief recurrent self-limiting disorders, which involve disturbances of both mood and monoamines; during the headache phase of the attack, the links with depression are most apparent. PMID- 8366472 TI - Dead reckoning in a small mammal: the evaluation of distance. AB - When hoarding food under infra-red light, golden hamsters Mesocricetus auratus W. return fairly directly from a feeding place to their nest site by evaluating and updating internal signals that they have generated during the previous outward journey to the feeding place. To test more specifically the animals' capacity to evaluate the linear components of the outward journey, the subjects were led from their (cone-shaped) nest to a feeding place along a detour which comprised either 2 (experiment 1) or 5 (experiment 2) segments; adjoining segments were at right angles to each other. In these conditions, the subjects remained significantly oriented towards the nest and therefore were capable of assessing translations as well as rotations during the outward journey. In experiment 3, the nest was removed after the hamsters had started the direct outward journey to the feeding place and the hamsters were rotated during the food uptake. The animals were no longer oriented towards the starting point of their journey, but nonetheless covered, along a fairly straight path, the correct homing distance, and then changed over to a circular search path. These results confirm that mammals can derive the linear components of an outward journey from self-generated signals and therefore are able to judge the homing distance without relying on cues from the environment. For a number of detour outward journeys, our data yield an unexpectedly good fit to Muller and Wehner's (1988) model of dead reckoning in ants. However, this is no longer the case when the outward journey contains an initial loop which brings the subject back to the starting point. These findings are discussed in terms of the biological significance and limitations of an approximate form of path integration. PMID- 8366473 TI - Acoustic response properties of single units in the torus semicircularis of the goldfish, Carassius auratus. AB - Single units of the goldfish torus semicircularis (TS) were recorded in response to pure tones. Response areas (RA) were obtained by recording the number of spikes evoked by tones in a range of frequencies and levels within the units' dynamic range. RAs gave estimates of best sensitivity (BS), characteristic frequency (CF), most excitatory frequency at each level (BF), and Q10dB. Peri stimulus-time histograms (PSTH), interspike interval histograms (ISIH), and period histograms were obtained at various frequencies and levels to describe the units' temporal response patterns. The distribution of CF is nonuniform with modes at 155, 455, and 855 Hz. The distribution of the coefficient of synchronization to standard tones is also nonuniform, revealing a dichotomy between units with little or no phase-locking and those that phase-lock strongly. PSTHs for units without significant phase-locking vary widely and include patterns resembling those of the mammalian auditory brainstem. Compared with saccular afferents, torus units tend to have lower spontaneous rates, greater sensitivity, and sharper tuning. Unlike saccular afferents, BF is independent of level for most torus units. Some torus units are similar to saccular afferents while others reveal significant transformations of information between the periphery and the midbrain. PMID- 8366474 TI - Independently evolved jamming avoidance responses employ identical computational algorithms: a behavioral study of the African electric fish, Gymnarchus niloticus. AB - An African electric fish, Gymnarchus, and a South American electric fish, Eigenmannia, are believed to have evolved their electrosensory systems independently. Both fishes, nevertheless, gradually shift the frequency of electric organ discharge away when they encounter a neighbor of a similar discharge frequency. Computational algorithms employed by Gymnarchus for this jamming avoidance response have been identified in this study for comparison with those of extensively studied Eigenmannia. 1. Gymnarchus determines whether it should raise or lower its discharge frequency based solely upon the signal mixture of its own reafferent and the exafferent signal from a neighbor, and does not internally refer to the pacemaker command signal which drives its own discharge. 2. The signal mixture is analyzed in terms of the time courses of amplitude modulation and phase modulation at each area of the body surface. 3. Phase of the signal mixture at each area is compared with that of another area for the detection of phase modulation. 4. Unambiguous information necessary for the jamming avoidance response is extracted by integrating information from all body areas each of which yields ambiguous information. 5. These computational features are identical to those of Eigenmannia, suggesting that the neural circuit for jamming avoidance responses may have evolved from preexisting mechanisms for electrolocation in both fishes. PMID- 8366475 TI - Processing a dynamic visual-spatial language: psycholinguistic studies of American Sign Language. AB - American Sign Language (ASL) has evolved within a completely different biological medium, using the hands and face rather than the vocal tract and perceived by eye rather than by ear. The research reviewed in this article addresses the consequences of this different modality for language processing, linguistic structure, and spatial cognition. Language modality appears to affect aspects of lexical recognition and the nature of the grammatical form used for reference. Select aspects of nonlinguistic spatial cognition (visual imagery and face discrimination) appear to be enhanced in deaf and hearing ASL signers. It is hypothesized that this enhancement is due to experience with a visual-spatial language and is tied to specific linguistic processing requirements (interpretation of grammatical facial expression, perspective transformations, and the use of topographic classifiers). In addition, adult deaf signers differ in the age at which they were first exposed to ASL during childhood. The effect of late acquisition of language on linguistic processing is investigated in several studies. The results show selective effects of late exposure to ASL on language processing, independent of grammatical knowledge. PMID- 8366476 TI - Processing syntactically ambiguous sentences: evidence from semantic priming. AB - In this paper, we report the results of a study which investigates the processing of syntactically ambiguous sentences. We examined the processing of sentences in which an embedded clause is interpretable as either a complement clause or as a relative clause, as in, for example, "The receptionist informed the doctor that the journalist had phoned about the events." The embedded clause in such sentences is typically analyzed as a complement to the verb informed, rather than as a relative clause modifying the doctor. A number of models parsing predict this is the only analysis ever considered, while others predict that both interpretations are computed in parallel. Using a cross-model semantic priming technique, we probed for activation of doctor just after the embedded verb. Since only the relative clause analysis contains a connection between the doctor and the embedded verb, we expected reactivation of doctor at that point only if the relative clause analysis were a viable option. Our results suggest that this is the case: Compared to priming in an ambiguous control sentence, a significant reactivation effect was obtained. These results are argued to support a model of parsing in which attachment of a clause may be delayed. PMID- 8366477 TI - The processing of homophonic homographs during reading: evidence from eye movement studies. AB - Research on the processing of homophonic homographs during reading is reviewed. The primary dependent variable considered was fixation time on target homographs. Both the characteristics of the homograph (whether there are two equally likely meanings or one dominant meaning) and the characteristics of the preceding context (whether it is neutral or contains disambiguating information) were varied. When the preceding context was neutral, readers fixated longer on balanced homographs (homographs having two equally likely meanings) than on control words matched on frequency and length, but didn't look any longer at biased homographs (homographs having a highly dominant meaning) than matched control words. However, when the preceding context disambiguated toward the subordinate meaning, readers fixated longer on a biased homograph than a matched control word (the subordinate bias effect). Attempts to eliminate the subordinate bias effect are described and the implications of our research for models of lexical ambiguity resolution are discussed. PMID- 8366478 TI - On the temporal course of gap-filling during comprehension of verbal passives. AB - The work presented in this paper examines the time course of antecedent reactivation following movement gaps found in passive sentences. Using a cross modal lexical priming technique, (re)activation of the subject noun phrase (NP) was examined at various critical points following the verb (near the posited gap) for verbal passive sentences and for active (control) sentences. Subjects made lexical decisions to visual targets that were presented at three locations during auditory sentence comprehension: immediately after the matrix verb, 500 msec after the verb, or 1000 msec after the verb. Responses to targets related to the subject NP were faster than those to controls during passive sentences (gap sentences), but not during active sentences (no-gap sentences), thus indicating that reactivation of the matrix subject did occur in the passive cases. Furthermore, the magnitude of the priming increased with distance and time from the verb, going from a nonsignificant trend at the verb to a highly significant effect at 1000 msec following the verb. These results are discussed in terms of both formal and processing models of language. PMID- 8366479 TI - Processing Dutch sentence structures. AB - This paper summarizes existing research on syntactic processing of Dutch sentences by adult native speakers of the language, with an eye to the implications of this work for a general theory of the human sentence processing mechanism (HSPM). The principles underlying the assignment of phrase structure and the binding of traces seem to be the same as those proposed for languages like English or Italian. For example, no delays of analysis exist in parsing the constituents of a phrase even if the phrase is head-final. Also, the obligatory topicalization of a constituent which is required in the highest clause of a Dutch sentence does not appear to result in trace postulation principles distinct from those operative in languages where topicalization is optional. The studies reviewed also address questions concerning the complexity of the dependency between a moved constituent and its trace as measured by the length of a path vs. the length of a chain, the processing of subject gaps following an overt complementizer, the complexity of interpreting an adjunct moved from an obligatory position, and the processing of discontinuous words. Though the studies do not pose a problem for pre-existing views of the HSPM, they do highlight certain areas of parsing theory which remain seriously underdeveloped. Foremost, perhaps, is the specification of the principles governing the architecture of the processing system, which ultimately should explain how the organization of the HSPM and its subcomponents results from acquiring the grammar of any particular language. PMID- 8366480 TI - Kaufman's theory of shame and identity in treating childhood sexual abuse in adults. AB - The competent nurse/therapist treats shame of the adult survivor of childhood sexual abuse. Shame must be identified, validated, and treated. Kaufman's Developmental Theory of Shame and Identity is easily applied to post-sexual-abuse phenomenon. Treatment principles can be incorporated in both individual and group therapy. Nurse/therapists are encouraged to further explore the role of shame in the psychopathology of the adult survivor of childhood sexual abuse. PMID- 8366481 TI - Depression in primary care: detection, diagnosis, and treatment. US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. AB - 1. About 15% of the general public will suffer from major depressive disorder sometime in their life, but fewer than one in three will be accurately diagnosed and treated. 2. About 10% to 15% or more of major depressive conditions are caused by general medical illnesses or other conditions. Generally, treat the associated condition first. If the depression persists after treatment, major depressive disorder should be diagnosed and treated. 3. In over 50% of depressed outpatients, antidepressant medication caused marked improvement or complete remission of their depressive symptoms. Several forms of short-term psychotherapy are effective for mild or moderate depression; combined treatment should be considered in certain situations. PMID- 8366483 TI - Nurses as researchers and research users. PMID- 8366482 TI - Homosexual support groups essential. PMID- 8366484 TI - Are you really my nurse, or are you a snake sheriff? PMID- 8366485 TI - Defending homosexuality. PMID- 8366486 TI - Half of nurses fear contracting AIDS. PMID- 8366487 TI - AIDS-related neuropsych problems highlighted. PMID- 8366488 TI - The World Trade Center disaster. Healing the unseen wounds. AB - 1. After the bombing of the World Trade Center in New York on February 26, 1993, hospitals were flooded with individuals who manifested not only medical problems, but also psychological trauma. 2. Various coping mechanisms were used by the disaster survivors. Some people were hysterical, while others were very quiet, almost catatonic, with blank affect and fixated posture. Some individuals, who remained strong during the ordeal, collapsed when they reached the hospital. 3. In attending the victims, nurses talked with them about the traumatic incident, the fear, and the angst--a cathartic process that helps people get better sooner. Such therapy is the key to healing unseen wounds. PMID- 8366489 TI - Informed consent: the patient's right to decide. AB - 1. The locus of mental health treatment has moved from the psychiatric hospital to the community; clients have become part of the general population as they move in and out of the mental health system. In response to this, health care providers and policymakers are trying to strike a balance between the provision of care and the restriction of patient rights while considering individual and societal interests. 2. Throughout the past three decades, the legal consensus of thought on informed consent has emphasized the rights of the patient, rather than emphasizing the medical profession's expertise. 3. Informed consent remains a controversial issue. An openness to modification must be maintained while acknowledging the actual meaning of informed consent. Informed consent is not a process by which one forces a person to do what is mandated, but an organized manner of providing information that will allow a reasoned decision to be made. PMID- 8366490 TI - Sexual harassment of health care students by patients. AB - 1. Forty percent of the 158 nursing and occupational therapy students surveyed reported being victims of sexual harassment. 2. When confronted with sexual advances or assaults, students used previously learned coping strategies. Thirty nine percent ignored the behavior or joked about it. 3. A training program was designed and implemented to make students feel better able--and more empowered- to handle sexual harassment. PMID- 8366491 TI - Music: making the connection with persons who are homeless. AB - 1. Persons who are homeless experience isolation and loneliness; many lack social skills or the ability to interact comfortably with others. A music program designed to increase socialization and relaxation of homeless persons using a multiservice shelter is described. 2. The use of music provides the psychiatric nurse an entry into therapeutic relationships and an opportunity to establish relationships with persons who often do not initiate contact with others. 3. Music promotes relaxation and interaction with others. Listening to music decreases loneliness and isolation. The music program was effective in fostering a sense of well-being and allowing the participants to join together in a meaningful activity. PMID- 8366492 TI - Orientation intervention for parents of adolescents after psychiatric hospitalization. AB - An orientation class has been devised to address the fears, uncertainties, and vulnerabilities of parents admitting their children to an adolescent psychiatric unit. This orientation class offers support and information to parents of adolescents admitted to Charter Rivers Hospital, a private psychiatric inpatient facility in Columbia, South Carolina, and is held during the first week of the adolescent's hospitalization. PMID- 8366493 TI - Suicide in the elderly: staying in control. AB - Suicide remains one of the major causes of death among the fastest growing segment of the US population--the elderly aged 65 and over. Individuals 65 and over comprised 12.4% of the population in 1988, but accounted for 20.9% of all reported suicides (McIntosh, 1992). The purpose of this qualitative study was to explore the meaning of suicide to the elderly and how suicide becomes an alternative for them. Results indicate that elderly subjects gave considerable thought to the end of their lives--including planning for death. For them, suicide was frequently viewed as a way of maintaining control over the dying process. In this study, the elderly described their views on who makes the decision about when death will occur, when suicide is acceptable, and how they would like others to respond to their suicidal ideation. Risk factors and causes of suicide in the elderly emerged from the data. PMID- 8366494 TI - What's happening to clinical nurse specialists in psychiatric mental health nursing? PMID- 8366496 TI - Link found between smoking and risk of endometrial cancer. PMID- 8366495 TI - PTs just as valuable as RNs. PMID- 8366498 TI - Staff numbers increase in specialty mental health organizations. PMID- 8366497 TI - Primary care providers need to look for and treat major depression. PMID- 8366499 TI - Persons with disabilities more likely to abuse chemical substances. PMID- 8366500 TI - The impact of media exposure on private hospitals. PMID- 8366501 TI - Group psychotherapy with the elderly. AB - 1. Group psychotherapy is an important and valid treatment modality for the psychiatrically impaired elderly. 2. The group format offers a normalizing, reality-based, and social context in which the patients may explore their concerns. 3. The therapist must be sensitive to issues such as sensory loss, debilitating illnesses, and death when leading geriatric psychotherapy groups. PMID- 8366502 TI - Chicken insulin discriminates between receptors for insulin and insulin-like growth factor I on centrally- and peripherally-derived glial cells. AB - Insulin and IGF-I receptors in G26-20 cells, derived from a mouse oligodendroglioma, and in RN-2 cells, derived from a rat Schwannoma, were characterized by specific binding to [125I]insulin and [125I]IGF-I respectively. In both cell lines, the Kd for insulin was 1.5 nM. Insulin receptor number was 33,000/cell for RN-2 cells and 17,000 receptors/cell for G26-20 cells. RN-2 cells have 700,000 IGF-I receptors/cell with a Kd of 2 nM while G26-20 cells have 60,000 receptors/cell with an affinity of 4.9 nM. However, the independence of these two receptor populations in each cell type was equivocal since the subunit structure of these receptors appears identical by electrophoresis. In both cell lines, competition with insulin analogs for [125I]insulin binding demonstrated chicken insulin > insulin > IGF-I. Competition for [125I]IGF-I binding showed that IGF-I was approximately 85-fold more potent than insulin. Chicken insulin was ineffective at all concentrations. Thus, chicken insulin can be used as a specific ligand to unequivocally discriminate between IGF-I and insulin receptors and effects. PMID- 8366503 TI - Binding of doxorubicin-conjugated transferrin to U937 cells. AB - Binding of transferrin (Trf) and its doxorubicin-conjugated forms (Conj) to U937 cells at 0 degrees C were compared using 125I-labelled Trf or Conj. The apparent binding affinity (Ka) of Conj to the surface of U937 cells was (1.9 +/- 0.4).10(8) l/mol; it is about 40% of that of Trf [(5.0 +/- 1.2).10(8) l/mol]. Binding of 125I-labelled ligands was blocked by the unlabelled ligands to the same degree, however, it was not blocked by a great excess of doxorubicin (Dox). N-ethylmaleimide caused about 10% inhibition while dithiothreitol was without effect. Dissociation of 125I-labelled ligands in the presence of different concentrations of unlabelled ligands (Trf and Conj in the all 4 variations) resulted in different R50 values (the concentration of the unlabelled ligand where 50% of the radiolabelled ligand was released). While Trf displaced Trf with an R50 value close to the binding affinity, Conj displacement by Conj occurred with much lower efficiency. The heterolog displacement experiments yielded R50 values in between the two extrema. These results suggest that 1) binding of Conj to the surface of cells is governed by the binding of the Trf part of Conj to the transferrin receptor, 2) -SH groups are not involved in the binding, and 3) a second interaction between the Conj and some constituent(s) of the plasma membrane may modify the binding of Conj in comparison to that of Trf. PMID- 8366504 TI - A model for the effect of estrogen antagonists on cooperative estradiol binding. AB - Partial agonists such as estriol and estrone have been reported to diminish or even eliminate the upward convexity of the Scatchard plot of the binding of labeled estradiol to estrogen receptor. This has been interpreted as agonist interference with the receptor dimerization induced by estradiol. In order to investigate how a partial agonist or antagonist might interfere with dimerization we have developed a theoretical mass-action law model, where soluble receptors can dimerize and bind to two different ligands. Special attention was devoted to manifestations of positive cooperativity to determine whether they could be modified by competition with a second ligand. This was done using a computer program that evaluated a large set of combinations of affinity constants in an effort to explore all possible situations. The model could reproduce the effect of a second ligand on the cooperative binding of estradiol to the estrogen receptor but only if the second ligand was anticooperative, which is not the case of estriol, estrone and tamoxifen. Furthermore, even when the Scatchard plot was linear, the model still required dimerization of the receptor in most of the cases, showing that the addition of an antagonist may eliminate the upward curvature of the Scatchard without truly eliminating dimerization or cooperativity. We conclude that the effect of a second ligand on the binding of labeled estradiol to estrogen receptor is not necessarily due to interference with dimerization and/or cooperativity. The inability of this model to fully explain the published data for estriol, estrone, clomiphene, and tamoxifen suggests that a more complex mechanism is involved. PMID- 8366506 TI - Psychosocial factors related to rheumatic diseases in childhood. AB - This review discusses those features of psychosocial adjustment which have been found associated with rheumatic diseases in children. In spite of the older literature and widely held intuitive beliefs, children with those diseases tend to do well in both psychological and social development and function. Those who do least well have risk factors which are those which impinge on the adjustments of any healthy child. Those who do best are those who have a strong social support system, particularly maternal competence. Children may cope in part by positive use of denial. Thus, interventions should be tailored to just those children and families at risk and must take into account the individual child's method of coping. It is argued that generalized interventions and education are unnecessary and may be harmful. PMID- 8366505 TI - Insulin and IGE-1 receptors in a human intestinal adenocarcinoma cell line (CACO 2): regulation of Na+ glucose transport across the brush border. AB - Both insulin and IGF-1 receptors are present in intestinal mucosal cells, although their role in this tissue is unclear. We have characterized these receptors in a human adenocarcinoma cell line, Caco-2, and examined their role in the regulation of glucose transport and absorption in these cells. The Caco-2 cells demonstrated specific insulin and IGF-1 receptors. They also bound cytochalasin B, suggesting the presence of a glucose transporter-like protein. When grown on membranes, the Caco-2 cells formed columnar, bipolar cells with tight junctions. The monolayer selectively transported D-glucose and methyl-D glucose, with complete exclusion of L-glucose, D-mannitol and inulin. The absorption of glucose across the monolayer occurred via a Na+/glucose cotransporter, as indicated by a change in short circuit current after addition of glucose to the apical membrane. When examined under several conditions, neither insulin nor IGF-1 had an affect on the transport of glucose across the Caco-2 monolayer, nor the production of lactate by the cells. It is concluded that the insulin and IGF-1 receptors of Caco-2 cells do not regulate glucose transport. PMID- 8366507 TI - Arthropathies of cystic fibrosis: case reports and review of the literature. AB - Patients with cystic fibrosis (CF) have demonstrated more arthritides with their longer life expectancy. The most common presentations have been that of an episodic arthritis or a hypertrophic osteoarthropathy. However, other arthropathies have been associated with CF. We now describe 3 new patients with CF and arthritis, and review the types of arthritis that may be found in patients with CF. This report is to increase awareness of the arthropathies that may be found in patients with CF so that proper evaluation, classification, and treatment may be facilitated. PMID- 8366508 TI - Lasers in medicine--a review. AB - Laser systems permit very high energy radiation of a single wavelength to be focused on a tiny spot, and have found application in many areas of engineering. They are also currently used in many branches of medicine. The fields reviewed here are ophthalmology, gynaecology, dermatology, otolaryngology, gastroenterology and physiotherapy. Lasers which are in wide use for medical applications include argon, YAG and carbon dioxide types. In many areas, lasers have been found to be more effective than conventional treatment methods with advantages including less blood loss, more accurate removal of unwanted tissue, shorter operating time and less postoperative pain. It is expected that the next decade will see the laser as an everyday tool in many more medical applications. PMID- 8366509 TI - Quantitative measurement of wall shear rate by pulsed Doppler ultrasound. AB - A 20 MHz pulsed Doppler ultrasound system was used to obtain steady flow velocity profiles in cylindrical tubes. A deconvolution technique was employed to improve the spatial resolution and the corrected results were compared with Poiseuille's theory. Frequency domain windowing was used to suppress noise in the deconvolution procedure, using a method which reduced distortions at the window boundaries. Wall shear rate was calculated from the measured velocity profiles both before and after deconvolution, and compared with theory to quantify the accuracy of the technique. The results illustrate the significant improvement provided by deconvolution, with the average error in measured wall shear rate reducing from 46 to 12% after applying the technique. Some of the discrepancy is in part attributed to the method used to determine wall shear rate. PMID- 8366510 TI - Computerized measurement of ciliary beat frequency. AB - We describe how ciliary beat frequency (CBF) of human respiratory epithelium in vitro can be robustly and quickly measured. The proven photometric technique has been improved by using a microcomputer to calculate and display the results. The software, which runs on an IBM-compatible PC, was developed using Borland Turbo Pascal and employs a fast Fourier transform routine to derive the CBF. Results are displayed almost as soon as a cell is identified under the microscope, and are in accordance with previous work. The technique can now be used diagnostically and for a variety of drug trials on respiratory epithelium. PMID- 8366511 TI - Hepatitis B versus AIDS. PMID- 8366512 TI - PCR fingerprinting microbes by random amplification of polymorphic DNA. PMID- 8366513 TI - Cellular immunity in pertussis. PMID- 8366514 TI - The serotypes of Streptococcus pyogenes present in Britain during 1980-1990 and their association with disease. AB - A total of 16,909 cultures of Streptococcus pyogenes (Lancefield group A) isolated in Britain during 1980-90 were examined for T- and M-protein antigens. One or other M antigen was detected in 92.6% of the strains. The numbers of isolates of some serotypes, such as M3 and M12, did not show great variation from year-to-year, whereas there were nationwide epidemics, extending over several years, caused by strains of serotypes M1 and M49. Isolates of serotypes M1 and M3 were associated particularly with invasive disease and fatal infections. Representatives of serotypes M80, M81 and the provisional types PT180, PT1658 and PT5757 were isolated most often from cases of pyoderma. Erythromycin resistance was detected in 30 serotypes but one half of all of the resistant isolates belonged to serotype M4. PMID- 8366515 TI - Identity of viridans streptococci isolated from cases of infective endocarditis. AB - The oral streptococci have undergone considerable taxonomic revision in recent years but there is still little information concerning associations between the newly defined species and disease. This study examined the identities of 47 strains of oral streptococci collected from 42 confirmed cases of infective endocarditis. By means of recently described physiological schemes, the most common species identified were Streptococcus sanguis sensu stricto (31.9%), S. oralis (29.8%) and S. gordonii (12.7%). Other related species including S. mitis and "S. parasanguis" were less common. This indicates that attention should be focused on S. sanguis sensu stricto and S. oralis when considering possible pathogenic mechanisms involved in viridans streptococcal endocarditis. PMID- 8366516 TI - Effect of co-aggregation on the pathogenicity of oral bacteria. AB - The pathogenicity of oral bacteria was studied by measuring the development of subcutaneous abscesses in mice after infection with Actinomyces viscosus and Streptococcus mitis either singly or as co-aggregated pairs. Heat-treated cells were also tested. The pathogenicity of the co-aggregates was examined in various viable and heat-treated combinations of the two bacterial species. More abscesses were formed by A. viscosus than S. mitis at all the bacterial concentrations tested. Also, abscess formation by co-aggregates of the two strains produced a higher percentage of abscess formation than those caused by infection with pure suspensions of A. viscosus or S. mitis. Co-aggregated cells were more resistant to phagocytosis and killing by neutrophils in vitro and in vivo. Furthermore, A. viscosus in co-aggregates were resistant to killing after engulfment by neutrophils. These results suggest that oral bacteria that are able to co aggregate may resist phagocytosis, and this ability may be linked with pathogenicity. PMID- 8366517 TI - Host response to coagulase-negative staphylococci in abscesses induced within mice. AB - A model whereby a known number of coagulase-negative staphylococci were packed into capillary tubes and implanted into the peritoneal cavity of mice proved to be a satisfactory method for generating abscesses that could be easily removed free of extraneous host tissue, and that permitted measurement of the survival of the organisms and accumulation of lipid in the lesion. Strains of S. epidermidis, S. schleiferi and S. lugdunensis, differing in their ability to produce fatty acid modifying enzyme (FAME) and lipase, were packed into either glass or plastic capillary tubes and used to generate abscesses. Abscesses produced by S. aureus served as comparators. Lipids accumulated within the abscesses caused by S. aureus in the same manner as previously described for the organism inoculated without tubes. Lipids also accumulated within abscesses produced by all the coagulase-negative staphylococci, but the rate of accumulation was slower and the lipid droplets were smaller than seen with S. aureus. The mobilisation of lipid did not differ in response to cocci in plastic or glass tubes. Strains of S. epidermidis and S. schleiferi producing FAME and lipase were better able to survive within abscesses than strains unable to produce these enzymes. However, FAME and lipase production did not appear to be the sole determinants of survival within abscesses. Regardless of whether they produced FAME and lipase, the two S. epidermidis strains were significantly better able to survive within plastic tubes than in glass tubes. No such difference was seen with S. aureus between plastic and glass tubes. PMID- 8366519 TI - An electronmicroscope study of glycopeptide antibiotic-resistant strains of Staphylococcus epidermidis. AB - Ultra-thin section transmission electronmicroscopy revealed that two of three glycopeptide-resistant strains of Staphylococcus epidermidis had abnormally thick cell walls, a finding consistent with the view that the reduction in susceptibility may result from the overproduction of glycopeptide binding sites within the cell-wall peptidoglycan. The third resistant strain had a slightly thickened cell wall with an irregular, roughened outline; this strain also underwent autolysis on prolonged incubation on blood agar and the resistance may be associated with abnormal cell-wall synthesis. Sub-MIC concentrations of vancomycin and teicoplanin caused surface damage to a proportion of cocci able to grow in the presence of antibiotic. Exposure to teicoplanin was additionally associated with the formation of filamentous forms and variable amounts of extracellular material. Transmission electronmicroscopy showed that both antibiotics exerted effects within the bacterial cytoplasm of the resistant strains that were not seen in an NCTC control strain: intracellular lamellae and structures resembling mesosomes were observed in the former. These effects were more noticeable in cocci exposed to vancomycin. Bacteria exposed to teicoplanin often showed abnormal septation and, in some preparations, a double-layered cell wall. PMID- 8366518 TI - Chemiluminescence of human polymorphonuclear leucocytes after stimulation with whole cells and cell-wall components of Staphylococcus epidermidis. AB - The purpose of this study was to define cell-wall components of Staphylococcus epidermidis responsible for activation of human polymorphonuclear leucocytes (PMNL). Metabolic activation of PMNL was determined by chemiluminescence (CL). Purified peptidoglycan (PG) induced a concentration-dependent metabolic burst in PMNL. The minimal concentration needed for CL induction was 1 microgram/ml. Comparison between different S. epidermidis strains showed variation in the capacity to induce CL in PMNL. Purified PG induced a higher CL response in PMNL than its intact parent strain; this effect was found in all S. epidermidis strains. Lipoteichoic acid (LTA), PG stem peptide and muramyldipeptide (MDP) did not induce CL; teichoic acid induced a CL response only at very high concentrations. No differences in CL inducing capacity were found between PG, crude cell walls, and purified cell walls of S. epidermidis. Sonication of PG strongly diminished CL-inducing capacity. PG treatment with mutanolysin immediately resulted in decreased CL-inducing capacity. Treatment of PG with S. aureus lytic enzyme (SALE) 10 micrograms/ml for up to 15 min enhanced the CL response to PMNL; a similar increase in CL was induced by PG treated with SALE at 1 microgram/ml for up to 120 min. Beyond these times, a continuous decrease in PG induced CL was observed. In conclusion, PG was found to be the major cell-wall component of S. epidermidis involved in CL induction. Moreover, a minimal fragment size or a specific tertiary structure of PG, or both, is required for metabolic activation of PMNL. PMID- 8366520 TI - Characterisation of Plesiomonas shigelloides strains that share type-specific antigen with Shigella flexneri 6 and common group 1 antigen with Shigella flexneri spp. and Shigella dysenteriae 1. AB - Three strains of Plesiomonas shigelloides isolated from patients with diarrhoea were agglutinated with Shigella flexneri 6 antiserum in slide and tube tests. All the strains were also agglutinated with a monoclonal antibody to the common group 1 antigen shared between S. flexneri serotypes and S. dysenteriae type 1. Further studies with one strain also showed sharing of antigenicity in an enzyme-linked immunosorbent assay. The results suggest that the strains share type-specific antigen with S. flexneri 6 and the common group 1 antigen with S. flexneri serotypes and S. dysenteriae 1. The sharing of antigens may have implications for cross-protection. One strain adhered to HEp-2 cell monolayers. None of the strains contained high mol. wt plasmids and there was no sequence homology with the invasiveness plasmid of Shigella spp. in DNA probe hybridisation. They were susceptible to the commonly used antibiotics. However, they possessed four other virulence-associated properties of Shigella spp. that included Congo-red binding, hydrophobicity, toxicity to HeLa cells and HEp-2 cell invasiveness (although they gave negative results in the Sereny test for invasiveness). These data suggest that the three unique strains might be considered pathogenic. Studies in animal models and human volunteers would be necessary to establish their pathogenic potential. PMID- 8366521 TI - Transferrin-binding ability of invasive and commensal isolates of Haemophilus spp. AB - Haemophilus influenzae type b expresses an inducible siderophore-independent iron acquisition system that depends on a direct interaction between human transferrin and specific iron-regulated transferrin-binding outer-membrane proteins. To evaluate the importance of this iron-acquisition system amongst haemophili, 156 isolates of Haemophilus spp. (78 commensal isolates and 78 isolates from invasive infections) were examined for their ability to bind transferrin. Of the 78 invasive isolates, all of which were H. influenzae type b, 71 (91%) were capable of binding transferrin, with 57 (73%) binding transferrin constitutively (i.e., even when grown in an iron-sufficient medium). In contrast, only 11 (14%) of the commensal isolates bound transferrin constitutively, with a further 16 (21%) binding transferrin only after growth in an iron-deficient medium. Of the 27 commensal strains that were capable of binding transferrin, 12 were H. parainfluenzae biotype III, 14 were non-typable H. influenzae, and one was H. parahaemolyticus. None of the H. influenzae type b invasive or commensal isolates showed evidence of siderophore production, but 50 (66%) of the remaining 76 commensal isolates appeared to produce an iron chelator. Thus, while not a universal characteristic, detectable transferrin-binding was associated strongly with H. influenzae type b isolates from invasive infections, and was also recognised for the first time in isolates of H. parainfluenzae and H. parahaemolyticus. PMID- 8366523 TI - Application of the polymerase chain reaction to the diagnosis of candidosis by amplification of an HSP 90 gene fragment. AB - A 317-base pair (bp) fragment of the Candida albicans heat shock protein 90 (HSP 90) gene was amplified by the polymerase chain reaction (PCR) for detection of C. albicans DNA in clinical specimens. One hundred specimens were examined including swabs (39), urines (36), peritoneal fluid (9), pus (8) and blood or serum (8): 23% gave positive results with routine culture, 31% with extended broth culture and 37% with PCR. The amplified product was identified by hybridisation with a radiolabelled internal probe and their restriction enzyme digest patterns (SspI, HaeIII, EcoRI, RsaI and XhoI), which could be predicted from the known sequence of HSP 90. C. albicans DNA gave the characteristic 317-bp band and specifically hybridised with restriction enzyme-digested candidal DNA. DNA from other sources intermittently gave multiple faint bands especially in the presence of high concentrations of DNA, but these could be readily distinguished. The method was sensitive to 50 pg of DNA (5 pg with radiolabelled probing) and 100 cfu of C. albicans. PMID- 8366522 TI - The cleavage of immunoglobulin G in vitro and in vivo by a proteinase secreted by the urinary tract pathogen Proteus mirabilis. AB - Eighteen different strains of Proteus mirabilis were all shown to produce an EDTA sensitive proteinase of c. 50 kDa that cleaved the heavy chain, but not the light chain, of IgG. Digestion of pure IgG with small amounts of pure P. mirabilis proteinase generated Fabc'2 and Fab'2 fragments; greater amounts generated Fab and Fc fragments that were comparable in size to those generated by pepsin and papain, respectively. Incubation of neutrophils with IgG digested with P. mirabilis proteinase or papain resulted in a marked decrease in the respiratory burst activity of the neutrophils that coincided with cleavage of the IgG into Fab and Fc fragments. Analysis of urine from patients with P. mirabilis urinary tract infection revealed in many the presence of Fab and Fc fragments of IgG indistinguishable in size from those generated by P. mirabilis proteinase. These results indicate that, in P. mirabilis urinary tract infections, the proteinase is secreted and cleaves IgG to fragments that have defective immune effector functions, thereby limiting the effectiveness of the immune response. PMID- 8366524 TI - The number of glomerular capillaries estimated by an unbiased and efficient stereological method. AB - A method for unbiased capillary number estimation based on the estimation of the Euler-Poincare characteristic or Euler number with the disector is evaluated. The generation of a new capillary creates a new loop in the capillary network corresponding to a change of exactly one unit in the Euler number of the network. In this way the Euler number has a one-to-one relationship to the number of capillaries in a network. In this report rat glomerular capillaries are counted. Three tissue blocks from each of 14 perfusion-fixed rat kidneys, aged between 5 days and 18 months, were uniformly sampled and embedded in Epon. Two complete glomerular profiles were sampled per block. Three consecutive sections were studied per glomerulus using the middle one to evaluate the topological events of the capillaries in the sampled glomerulus. The use of complete glomerular profiles eliminated problems with the edges, whereas the disector ensured unbiased sampling in the third dimension. Estimates per animal were weighted averages over blocks, the weights being half the number of glomerular profiles in a section from a block. The number of capillaries in a glomerulus is the mean Euler number per disector volume multiplied by the mean volume of glomeruli obtained by the fractionator. The observed coefficient of variation between animals was 18.3% for the estimated number of capillaries per glomerulus, and the observed coefficient of error at the level of blocks within animals was 14.7%. The exact capillary number from the node-branch network of two reconstructed glomeruli equalled the capillary number obtained by the total Euler number from the same glomeruli. This shows in an applied example, as would be expected, that the estimation of capillary number using the Euler number is unbiased and independent of the direction of sectioning. PMID- 8366525 TI - Computed three-dimensional reconstruction of median-eminence capillary modules: image alignment and correlation. AB - Image alignment is an absolute requirement for three-dimensional (3-D) reconstruction from serial sections, and Fourier correlation is the most powerful way to compute alignments. The rotational and translational components of misalignment can be corrected by an iterative correlation procedure, but for images having significant differences, alignment can fail with a likelihood proportional to the extent of the differences. We found that translational correction was determined much more reliably when low-pass filters were applied to the product transforms from which the correlations were calculated. Rotational corrections based on polar analyses of the auto-correlations of the images instead of on the images directly contributed to more accurate alignments. These methods were used to generate 3-D reconstructions of brain capillary modules from serial-section mosaics of digitized transmission electron micrographs. PMID- 8366526 TI - Degenerative cervical disc disease. AB - Degenerative cervical disc disease is a very common problem with most problems being resolved with conservative measures. Patients can present with a wide variation of complaints from neck pain to myelopathy secondary to spinal cord compression. In those patients requiring surgery for arm pain and myelopathy, the results are quite favorable. PMID- 8366527 TI - Case records of the Department of Medicine University of Mississippi Medical Center. Renal cell carcinoma and amyloidosis in a menorrhagic female. PMID- 8366528 TI - Hospice care. Interview by Linda Edwards. PMID- 8366529 TI - You know the plan is in trouble when she comes to the AMA. PMID- 8366530 TI - Developing a response to national health-care reform. PMID- 8366532 TI - Sexually transmitted disease among adolescents in the juvenile justice system of the District of Columbia. AB - Disenfranchised youth are known to be at high risk for sexually transmitted infections. A study was conducted to validate the screening for sexually transmitted disease (STD) among adolescents under court jurisdiction, to characterize variables associated with STD among this group, and to contrast and compare the characteristics of STD among incarcerated youth as opposed to those in alternative court-sponsored facilities. Sixty teenagers referred to an outpatient adolescent clinic for court-ordered physical examination were tested for infection with syphilis. Fifty-four were tested for gonorrhea and chlamydia. The overall rates for gonorrhea and chlamydia among the group were an identical 9.2%. Six percent of the study population were diagnosed with syphilis infection. While only 17% of the youths were female, they accounted for over half of all infections with gonorrhea and chlamydia. All cases of sexually transmitted bacterial infections were found in youth residing in alternative court-sponsored facilities. PMID- 8366531 TI - Clinical practice guidelines: a key to improving health care for all populations. PMID- 8366533 TI - The relationship of organism pathogenicity and route of acquisition to antimicrobial susceptibilities. AB - Three hundred forty-eight isolates of methicillin-resistant Staphylococcus aureus were classified as representing nosocomial or community acquired infection or colonization. They were then tested against 11 antimicrobials, and the percentage of isolates that were susceptible to each antimicrobial was compared statistically among the classes. There were statistically significant (P value < 0.05, chi-square analysis) differences among isolates from several classes for chloramphenicol, imipenem, tetracycline, sulfamethoxazole-trimethoprim, ciprofloxacin, and gentamicin. PMID- 8366534 TI - The clinical and radiological evaluation of primary brain tumors in children, Part I: Clinical evaluation. AB - In Part I of this article, we present our data collected over the past 8 years on the clinical evaluations of pediatric brain tumors with an emphasis placed on the more common neoplasms. Our data consists of 385 children ranging in age from newborn to 18 years. The majority of children presented with signs of raised intracranial pressure (including nausea, vomiting, and headaches), seizures or other focal neurologic deficits. Five percent of our children presented to outlying hospitals with symptoms that retrospectively turned out to be due to brain neoplasms but were misdiagnosed as "gastroenteritis," "viral upper respiratory tract infection," or even viral meningitis. These delays in diagnosis can cause serious negative outcomes for these patients and can be avoided through more careful neurologic and ophthalmologic examination at the time of first presentation. Central nervous system neoplasms are not uncommon in children and any child presenting with nausea, vomiting, and headaches should raise the suspicion of a primary brain tumor and should receive both a thorough neurologic exam and screening for papilledema. If papilledema is present, these children should be referred for proper neuroradiologic evaluation (which will be addressed in Part II. PMID- 8366535 TI - Left ventricular mass index and coronary artery disease in hypertensive black males. AB - Thallium-201 stress scintigraphy (TSS) and echocardiography were performed on 60 consecutive black male hypertensives and compared to 60 sex-, race-, and age matched controls. We found a higher prevalence of left ventricular hypertrophy with repolarization abnormality in the hypertensive group; 32 of 60 (53%), compared to 10 of 60 (17%) of the controls, P < .05. Echocardiographically determined left ventricular mass index revealed a significantly higher mean value in the hypertensive group of 147 +/- 57 compared to 124 +/- 34 in the control group, P < .001. Thirty-one of 60 (52%) of the hypertensive group had a normal TSS compared to 22 of 60 (37%) of the controls. A total of 68 (38 fixed and 30 reversible) perfusion defects were noted in the hypertensive group compared to 74 (55 fixed and 19 reversible) in the controls. The severity of clinical syndromes associated with myocardial ischemia were noted in increased incidence in the presence of left ventricular hypertrophy and left ventricular mass index was noted to be predictive of severity of coronary disease independent of the standard risk factors. PMID- 8366536 TI - Diffuse abdominal wall cellulitis in ascending omphalitis--a lethal association in neonatal necrotizing fasciitis. AB - Necrotizing fasciitis is a grave complication of ascending omphalitis in the neonate, but because it is rare some of the signs are not well documented. Rapidly progressive anterior abdominal wall edema and cellulitis were noted in 16 patients who were clinically diagnosed with necrotizing fasciitis. Fifteen of these patients died soon after emergence of anterior abdominal wall edema and cellulitis. The appearance of anterior abdominal edema and cellulitis in a patient with ascending omphalitis has serious implications and demands intensive care if the patient is to survive. PMID- 8366537 TI - Management of extraperitoneal rectal injuries. AB - Twenty-eight consecutive extraperitoneal rectal injuries for a period of 34 months ending in May 1990 were reviewed retrospectively. All injuries were due to penetrating gunshot wounds. The rectal exam was positive in 75% of patients versus 80.8% with proctosigmoidoscopy. All 28 patients had diversion of the fecal stream. Diverting colostomies were performed in 17 patients, Hartmann's colostomies in 7 patients, and proximal loop colostomies in 4 patients. Presacral drainage was used in 25 patients (89.3%). Distal irrigation was performed in 13 patients (46.4%) and primary repair in 9 patients (32.1%). There was one infectious complication (3.6%) and no deaths (0%). Fecal diversion and presacral drainage are the mainstay of therapy for civilian rectal injuries. The importance of distal irrigation of the rectum has not been established. Primary repair of the rectum has no effect on morbidity and mortality. PMID- 8366538 TI - Laser excision of hypopharyngeal lesions using a transoral approach. AB - A transoral technique for the excision of primary hypopharyngeal, posterior pharyngeal, and lateral pharyngeal wall tumors using the CO(2) or KTP laser and an operating microscope is presented. PMID- 8366539 TI - Myxedema masking primary hyperparathyroidism. AB - This article describes a case of primary hyperparathyroidism that was unmasked in a 63-year-old female after the initiation of replacement therapy with L-thyroxine for myxedema. PMID- 8366540 TI - An unusual case of priapism. AB - A case of sickle cell disease with 63 documented episodes of priapism that were managed medically is presented. The case is very unusual because of the fact that despite so many episodes of priapism, he did not lose sexual potency. On the contrary, over a period of time, his penis hypertrophied. To the best of our knowledge, this is the first such case with so many episodes of priapism reported in the English literature. We present a hypothesis for such unusual occurrence. PMID- 8366542 TI - Grip strength: relationship to shoulder position in normal subjects. AB - The objective of this study was to evaluate the effect of shoulder position on grip strength. A Jamar dynamometer was used to measure the grip strength of 160 subjects (80 males and 80 females), stratified on both sex and age, in the four testing positions. For each of the tests of grip strength, the subject stood with the shoulder adducted and neutrally rotated while the forearm and wrist were held in the neutral position. The four hand strength tests consisted of three positions in which the elbow was maintained in full extension combined with varying degrees of shoulder flexion (i.e., 0 degree, 90 degrees, and 180 degrees) and of one position in which the elbow was flexed at 90 degrees with the shoulder in 0 degree of flexion. Only the dominant hand was tested. The results showed that the highest mean grip strength measurement was recorded when the shoulder was positioned at 180 degrees of flexion with elbow in full extension; whereas the position of 90 degrees elbow flexion with shoulder in 0 degree of flexion had the lowest grip strength score. In addition, the grip strength measured with the elbow in extension, regardless of shoulder position (i.e., 0 degree, 90 degrees, and 180 degrees of flexion), was significantly higher than when the elbow was flexed at 90 degrees with the shoulder positioned at 0 degree of flexion. Finally, grip strength differed significantly for both sexes and for each age group. The findings are valuable in the evaluation and rehabilitation training of hand injured patients. PMID- 8366541 TI - DC General--its neuro-history in the last half century. PMID- 8366543 TI - Crude drug (zingiberaceae) enhancement of percutaneous absorption of indomethacin: in vitro and in vivo permeation. AB - To improve drug permeation through skin, extracts of crude drugs were evaluated using in vitro and in vivo penetration techniques with rabbit skin as a model membrane. The acetone extract of Amomum cardamomum (ae-AC) and Elettaria cardamomum (ae-EC) had the best effect in enhancing the penetration of Indomethacin (IDM). The flux of IDM for the formulation containing ae-AC from pH 7.4 buffer-alcohol donor solution was 3.6 times higher than that from the 50% alcohol donor solution. In order to confirm enhancer/skin interaction, a microscopic study was carried out in order to determine the presence of physical evidence in the skin caused by enhancers. A pharmacokinetic model of percutaneous absorption of IDM after topical administration was employed on the assumption of a zero-order penetration rate through the stratum corneum followed by absorption into the blood by a first-order process. Good correlation was observed between the experimental data point and simulated plasma concentration. From the results of the study, the in vitro permeability coefficient correlates with the in vivo penetration rate through the stratum corneum. PMID- 8366544 TI - The effects of radiation therapy on salivary function in patients with head and neck cancer. AB - Eighty nasopharyngeal carcinoma (NPC) patients and another eighty head and neck cancer (HNC, non-NPC) patients were enrolled as two experimental groups to study their salivary function by using Tc99m sialography. Twenty healthy subjects were also employed as a control group. The patients received an intravenous injection of 4 mCi of 99mTc-pertechnetate (Tc-99mO4-). The data were collected at a rate of 1 frame per 15 seconds for the total time of 30 minutes, and the patients received stimulations for salivary secretion by ingesting 0.5cc of lemon juice 15 min after the start of data acquisition. The salivary function was measured on Pre-RT (radiation therapy), During-RT and Post-RT periods. The results showed no statistical significance for maximum uptake (%) and excretion rate (%) between Control and Pre-RT group on parotid or submandibular glands function. This was the same in the age groups (age below 40 and age above 40) and sex groups. The NPC group had a decreasing maximum uptake (%) 3 months after RT on both parotid glands and submandibular glands, whereas the HNC group showed no obvious difference. The excretion rate (%) of both parotid and submandibular glands reached its lowest mark after 3-6 months in both the NPC and HNC groups and then started to recover progressively. For NPC patients, the radiation damage to the parotid glands was greater than to the submandibular glands, whereas the effect was reversed on HNC patients. It is important that the radiation therapist should preserve salivary function whenever possible. PMID- 8366545 TI - The effect of shift system on sleep quality, sleep quantity, psychological disturbance, and family function of workers in Taiwan. AB - This study was designed to examine whether there were any differences in sleep quality and quantity between rotating shift workers and permanent day workers. The subjects of this study consisted of 419 rotating shift workers and 468 permanent day workers. The Chinese Health Questionnaire (CHQ-12) and Family APGAR Index were used to collect information concerning psychological disturbances and family dysfunctions. The results showed that, compared to the permanent day workers, sleep quality and quantity were poorer for the rotating shift workers. The rotating shift workers often had more psychological disturbances and family dysfunctions than permanent day workers. PMID- 8366546 TI - [Comparison of Enterobius vermicularis infection among preschool children in Ta Liao District of Kaohsiung County with that in Kaohsiung City]. AB - To compare the rate of E. vermicularis infection among preschool children in Ta Liao District of Kaohsiung County, with that in Kaohsiung City, a total of 532 preschool children from 7 kindergartens in Ta-Liao District, Kaohsiung County and 544 preschool children from Kaohsiung City kindergartens were randomly collected. The preschool children were examined for E. vermicularis infection with a scotch tape perianal swab technique (S.T.P.S.T.). After examination, the preschool childrens' parents were also interviewed. The interview included the following factors: personal data of the preschool children (age, sex and birthplace); the size of the living quarters (measured in "Ping") and the number of rooms in the living quarters; the play area floor material (e.g. carpet, wood, tile, etc.); the total number of family members; the distribution of family members in bedrooms; the frequency of finger-sucking and the frequency of hand-washing before eating meals and after using toilets; the preschool childrens' primary caregiver; the occupations of both parents; and the means and times of bathing. The obtained data were analyzed and E. vermicularis infection among the preschool children in Ta-Liao District and Kaohsiung City were compared using the Mantel Haenszel statistical program in Statistical Analysis System (S.A.S) software. The present results indicated that the rate of E. vermicularis infection among preschool children was higher in Ta-Liao District than in Kaohsiung City. PMID- 8366547 TI - [Comparison of various patterns of chopstick use and functional performance]. AB - Three hundred and ninety-seven normal adult subjects were tested in order to investigate the prevalences of various patterns of chopstick-use. Manipulation speed was also compared. According to the movement of the fingers, finger positions and contact areas, we can divide the various chopstick-use patterns into 3 basic patterns with 13 variations. Prevalences of the 3 basic patterns were palmar prehension (68.5%), lateral prehension (14.2%), and dynamic palmar prehension (17.3%). There was a statistically significant difference in manipulation speed among the 3 basic patterns. The influence of sex and age on manipulation speed was also analyzed for each of the 3 basic chopstick-use patterns. The results of this study will serve as a reference for occupational therapists in the evaluation and training for eating activities. PMID- 8366548 TI - [Contralateral hearing and tympanoplasty]. AB - The contralateral hearing level of the operated ear is closely related to its preoperative hearing level, and is an important index to the success of tympanoplasty. We analysed 146 cases of chronic otitis media who had received tympanoplasty by the same surgeon at Kaohsiung Medical College Hospital. From the results of pure tone audiometry, we divided the hearing acuity into the following 5 categories: normal hearing, mild hearing loss, moderate hearing loss, severe hearing loss, and deafness. Referring to the categories of contralateral hearing, we discuss the preoperative hearing level of the operated ear, the occurrence of cholesteatoma, the type of the tympanoplasty, and the auditory gain of the operation. While 23.97% cases had moderate or severe loss of contralateral hearing, their hearing acuity of the operated ear was also poor. Most of cases with normal contralateral hearing received type I tympanoplasty. Compared to the above group, half of the cases with moderate or severe contralateral hearing loss received type III or type IV operations to reconstruct the ossicle chain. Though the type I cases had more hearing gains than the type III cases, those with moderate contralateral hearing loss had good results from the type III tympanoplasty. We also found the cases with cholesteatoma in the operated ear had better contralateral hearing in the contralateral ear than the cases without cholesteatoma. The decision to perform tympanoplasty in cases of the better hearing ear with poor contralateral hearing should be very carefully made so as to improve the postoperative social life of the patients. PMID- 8366549 TI - [Topics and informed consent]. PMID- 8366550 TI - [Anesthesia and laryngeal muscle, especially intrinsic laryngeal muscles]. AB - The intrinsic laryngeal muscles are highly specialized for phonation, respiration and sphincter activity. The muscles are disposed between three unpaired cartilages (the thyroid, cricothyroid and epiglottic) and the paired arytenoid cartilages. These laryngeal muscles, which are striated in character, are bilaterally disposed and can be grouped as adductors and abductors of the glottis and tensors of the vocal cords. The motor neurons for the intrinsic laryngeal muscles are located in the caudal half of the nucleus ambiguous. The intrinsic laryngeal muscles receive motor nerve supply from the external branches of the superior laryngeal and recurrent nerves on each side. The external branch of the superior laryngeal nerve serves in motor innervation of the cricothyroid muscle, while the other laryngeal muscles receive a motor innervation from the recurrent nerve. Compared with limb skeletal muscles, the intrinsic laryngeal muscle have unique morphologic and histochemical characteristics. In general, the intrinsic laryngeal muscle fibers contain greater percentages of histochemically type 1 fibers than limb skeletal muscles. In addition, morphometrical studies of the subneural apparatus at the neuromuscular junctions of the intrinsic laryngeal muscles demonstrate the difference between the morphological features of the nerve endings and the distribution pattern of the motor end-plates of the laryngeal muscles and those of the limb skeletal muscles. Finally, the influence of anesthetic drugs including neuromuscular blocking agents on the intrinsic laryngeal muscles is discussed. The gross anatomical features such as the motor innervation, localization of the neurons for the motor nerve fibers, and arrangement and characteristics of the motor end-plates of the intrinsic laryngeal muscles are described based on a review of literature and our current investigations. PMID- 8366551 TI - [Anesthesia with spinal cord stimulation--II). The effects on the cardiovascular function and the level of the plasma catecholamines]. AB - In 78 patients who underwent general anesthesia and surgery with nitrous oxide (50-60%) and SCS, SCS decreased heart rate and blood pressure. Both the skin temperature and the amplitude of plethysmographic wave of a left finger increased with SCS. Among plasma catecholamines, only epinephrine level rose significantly with SCS. These results suggest that in addition to the analgesic action, SCS may have sympathetic blocking action, but not suppressive action on release of epinephrine from adrenal gland. PMID- 8366552 TI - [Changes in respiration and hemodynamics during open heart surgery without blood transfusion]. AB - The changes in respiration and hemodynamics during open heart surgery were studied in 25 patients undergoing coronary artery bypass grafting without blood transfusion. The respiratory and circulatory parameters were measured at the time of anesthetic induction and after cardiopulmonary bypass (CPB). The values after CPB were compared with those at the time of anesthetic induction. The values of HR, CI, SVI and mPAP increased, and the values of mAP, SVRI and PVRI decreased after CPB. The PaO2, BE and pH decreased but PaCO2, A-aDO2 and QS/QT increased after CPB. Although VO2I and DO2I increased after CPB, OER (VO2I/DO2I) was unchanged. Arterial lactate, pyruvate and cortisol levels increased after weaning from CPB. Hemodynamics during open heart surgery without blood transfusion showed hyperdynamic state after CPB. Hypoxia was not evident in the peripheral tissue. This suggests that the depression of the oxygen delivery with hemodilution is compensated by hyperdynamic circulation. Coronary artery bypass grafting without blood transfusion seems to offer no clinical problems. PMID- 8366553 TI - [Effect of anesthetic methods on hemodynamics and metabolic changes caused by hepatic ischemia and reperfusion in pigs]. AB - The effects of halothane, isoflurane and epidural anesthesia combined with isoflurane on hemodynamic and metabolic changes caused by hepatic ischemia and reperfusion were studied in 16 pigs. Hepatic arterial and portal venous blood flows were measured electromagnetically. Lactate pyruvate ratio (L/P) and arterial ketone body ratio (AKBR) were calculated as markers of hepatic aerobic metabolism. Total hepatic blood flow (THBF), cardiac output (CO) and THBF/CO showed no significant differences among three anesthetic methods in ischemic and reperfusion period. In the group with epidural anesthesia combined with isoflurane, L/P was significantly lower and AKBR was significantly higher compared with the data obtained in ischemic period. However, hepatic metabolism was severely disturbed after the reperfusion of the liver in all three groups. Especially, halothane group showed the most remarkable decrease in AKBR. In summary, epidural anesthesia will be useful for aerobic hepatic metabolism because of inhibition of the release of endogenous cathecolamines, but hepatic metabolism will not be maintained following hepatic ischemia and reperfusion. PMID- 8366554 TI - [Evaluation of skin temperature of patients under spinal anesthesia during cesarean section]. AB - Temperature changes of the first finger and toe were evaluated in patients under spinal anesthesia. One hundred and thirty female patients who were to undergo cesarean section were selected for this study. During spinal anesthesia the changes in skin temperature were classified in three patterns. The first pattern showed a rise of the first finger and toe temperature just after intrathecal injection of 0.3% dibucaine (hand and foot type, n = 77). The second pattern showed only a rise of the first toe temperature (foot type, n = 55), and the third pattern showed no change in the first finger and toe temperature (unchanged type, n = 3). The results of cold description tests were T5 +/- 2 (mean +/- SD) in hand and foot type, T8 +/- 2 in foot type and L1 +/- 6 in unchanged type. The skin temperature pattern was affected by the position of the patient. When the patients were placed in a head down position, 38 cases of foot type showed a rise of the first finger temperature, and 1 case of unchanged type showed a rise of the first finger and toe temperature. In these cases the operative procedure was done under spinal anesthesia. The remaining 4 cases of foot type and 2 cases of unchanged type needed another anesthetic method. In cesarean section under spinal anesthesia, skin temperature pattern of hand and foot type seems desirable. Simultaneous monitoring of hand and foot (first fingertip temperature) seems to be useful to evaluate the height of spinal anesthesia. PMID- 8366555 TI - [Effects of induced hypotension on perioperative renal and hepatic functions]. AB - Hypotensive anesthesia induced by trimethaphan was maintained at 70-79 mmHg of the systolic radial artery pressure for two hours in 35 patients undergoing spherical acetabul osteotomy. The creatinine clearance, free water clearance, fractional sodium excretion, urine volume, urinary excretion of NAG and levels of gamma-GTP, serum GOT and GPT were measured perioperatively. The creatinine clearance, free water clearance and urine volume decreased by 50% during surgery but recovered to normal values on the third day after surgery. The fractional sodium excretion remained unchanged during and after surgery. The urinary NAG activity increased from 3 +/- a (SD) to 10 +/- 5 U.g-1 and gamma-GTP activity increased from 23 +/- 7 to 33 +/- 13 U.g-1 during surgery, and these remained at high levels for three days after surgery. The serum GOT and GPT levels were within normal ranges for 21 postoperative days. The increase in urinary enzyme activities during and after surgery indicates that mild damage of renal tubular cells has occurred during hypotensive anesthesia. PMID- 8366556 TI - [Effects of air injection on hemodynamics and sympathetic nerve activity in urethane-anesthetized rabbits]. AB - We designed this experiment to evaluate effects of intravenous bolus injection of air (0.5 ml.kg-1) on systemic blood pressure (SBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethane-anesthetized rabbits. Animals were divided into the following three groups: animals with neuraxis intact (I group, N = 5), cervical vagotomized animals (V group, N = 5) and sinoaortic denervated animals (SAD group, N = 4). All animals were placed on the right-side down position to avoid effects of the posture throughout the experiments of air embolism. In the I group, air caused profound hypotension (from 95 +/- 10 to 54 +/- 15 mmHg) associated with a significant increase in CVP (from 2 +/- 2 to 7 +/- 3 mmHg) twenty seconds after the injection of air. In spite of the significant hypotension, RNA response did not show any increase for twenty seconds. This response was followed by an augmentation in RNA thirty seconds after air injection. In contrast, vagotomized animals exhibited a significant RNA increase (147 +/- 11% of the control) in response to a decrease in SBP (from 93 +/- 6 to 78 +/- 5 mmHg) and an increase in CVP ten seconds after the administration of air. In SAD group, a rapid and remarkable decline in SBP (from 85 +/- 13 to 47 +/ 12 mmHg) occurred ten seconds after the injection of air. Despite this hypotension, RNA decreased nearly to a noise level after administration of air.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366557 TI - [Transdermal application of 10% lidocaine-gel for management of pain associated with herpes zoster]. AB - We have developed transdermally applicable 10% lidocaine aqueous gel containing an absorption promoter and applied it for 15 patients suffering from severe pain in acute or subacute phase of herpes zoster. The patients, consisting of 7 males and 8 females with a mean age 58.5 +/- 13.0 (SD) yrs, had skin eruptions of herpes zoster for the past 2 months. Lidocaine-gel was applied locally to the diseased skin with or without an occlusive dressing. In 14 of the 15 patients (93%), a remarkable reduction of pain (below 10% of pretreatment level) was obtained after 9.9 +/- 5.6 (SD) times of lidocaine-gel treatments. There was no adverse systemic reactions or local skin damages. None of them developed post herpetic neuralgia. The lidocaine-gel treatment appears to be very useful for reduction of pain associated with acute or subacute phase of herpes zoster. PMID- 8366558 TI - [Treatment of cancer pain with the percutaneous electrocoagulation of spinal nerves]. AB - To our knowledge, this is the first report of high-frequency thermocoagulation applied to the spinal root. We treated 34 patients suffering from cancer pain with this technique. Among these patients, cancer pain occurred due to intrapelvic metastasis in 11 patients, and 13 complained of chest pain due to cancer. Every patient was considered to have good or excellent response when his or her pain score was reduced to 6 points or less from the score before thermocoagulation; 10 points. Based on this criterion, 54.5% and 30.8% of the above-mentioned patients showed good and excellent responses respectively one month after treatment. This technique, therefore, was considered to be effective with less side effects compared with other nerve blocking techniques. PMID- 8366559 TI - [Postoperative pain relief by preanesthetic administration of buprenorphine suppository in elective mastectomy]. AB - Seventy female patients scheduled for elective mastectomy were divided into three groups: Buprenorphine suppository (BPS) 0.4 mg group (n = 29); BPS 0.2 mg (n = 23) group; and control (scopolia extract and tannic acid suppository) group (n = 18). Suppositories were administered rectally to patients of each group one hour before induction of anesthesia. Plasma buprenorphine concentrations, sedation scores at entering the operating room, postoperative pain scores and side effects were evaluated. There were no significant differences in sedation effects of suppository among the three groups. Although there were significant differences in pain scores except at the time when patients left the operating room between BPS 0.2 mg group and the control group, postoperative pain relief in BPS 0.2 mg group was judged not enough. However, postoperative pain relief was more satisfactory in the BPS 0.4 mg group. Plasma concentrations of the BPS 0.4 mg group were higher than those of the BPS 0.2 mg group. Although nausea and vomiting were observed in 5 patients (17.2%) of the BPS 0.4 mg group and 4 patients (17.4%) of the BPS 0.2 mg group, respiratory depression and changes in blood pressure and heart rate were not observed in all groups. In conclusion, preanesthetic administration of the BPS 0.4 mg seemed to be useful for postoperative pain relief after elective mastectomy. PMID- 8366561 TI - [EEG pattern during total intravenous anesthesia with droperidol, fentanyl and ketamine]. AB - We evaluated EEG pattern during total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK). Four surgical patients, ranged in age from 35 to 43, were the subjects of this study. Two male underwent oral or orthopedic surgery and the other two female patients underwent gynecological surgery. They were all free from hepato-renal dysfunction and central nervous system disorders. For the induction of anesthesia, droperidol 0.06-0.1 ml.kg-1, fentanyl 2-4 micrograms.kg 1, and ketamine 1.0-1.5 mg.kg-1 were slowly administered intravenously. A total dose of 5-15 micrograms.kg-1 of fentanyl was given intravenously with continuous infusion of ketamine 2 mg.kg-1.h-1 during the surgical procedure. The total amounts of fentanyl and ketamine administered were 4.9-22.2 micrograms.kg-1 and 240-340 mg.kg-1, respectively. We used HZI'Brain Function Monitoring system to evaluate their EEG patterns. When adequate depth of anesthesia was obtained as clinically evaluated by vital signs, theta wave pattern was dominant on the EEG tracings in any of these patients. DFK anesthesia would provide a stable anesthetic course, if those drugs are administered adequately considering vital signs including systemic blood pressure, heart rate, lacrimation and involuntary muscle movements of the face and extremities. PMID- 8366560 TI - [Immobilization of a sensitive plant, Mimosa pudica L., by volatile anesthetics]. AB - The disappearance of thigmonastic mobility of a sensitive plant, Mimosa pudica L., caused by volatile anesthetic agents such as methoxyflurane, chloroform, halothane, enflurane or sevoflurane revealed that the response to anesthetic agents in plants maybe similar to that in animals. In terms of reversible anesthesia, animals seem to equal plants in order of potency of anesthetics, and the minimum immobilizing concentration (MIC; %) in the plant shows a good correlation with MAC in the human (MICplant = 5.8 MAChuman + 0.01, r2 = 0.946). These phenomena suggest the existence of a certain common mechanism in anesthesia between animals and plants. PMID- 8366562 TI - [Anesthetic management of a neonate with critical pulmonary valve stenosis for balloon pulmonary valvuloplasty]. AB - We administered general anesthesia for balloon pulmonary valvuloplasty (BPV) to a 19 day-old male infant, weighing 2,789g, with critical pulmonary stenosis. The patient had severe cyanosis and mild right heart failure. Atropine (0.01 mg.kg-1) was administered intravenously immediately before induction of anesthesia. Pancuronium (0.4 mg) was used to facilitate endotracheal intubation and for the subsequent control of ventilation. Anesthesia was maintained with oxygen and enflurane (0.25 approximately 0.5%) supplemented with intravenous administration of fentanyl (1.5 micrograms.kg-1). During catheterization for balloon pulmonary valvuloplasty, SpO2 and blood pressure decreased temporarily to 35% and 50 mmHg, respectively. Several side effects of balloon inflation have been reported, such as bradycardia, arrhythmia, and the decrease in systemic blood pressure and arterial oxygen saturation, mainly due to the occlusion of pulmonary blood flow. Therefore, it might be recommended that BPV should be performed under stable state of general anesthesia with continuous monitorings of especially ECG, arterial blood pressure, central temperature, SpO2, ETCO2 and urine output. PMID- 8366563 TI - [Anesthesia for severely burned patients--23 operations in 8 burned patients]. AB - Severely burned patients require repeated debridement or skin grafting soon after the burn injury until the closure of the injury. We retrospectively examined 23 operations in 8 severely burned patients who had undergone debridement or skin grafting more than twice within 30 days. We classified 23 operations into 1st to 4th categories according to days after the burn injury and compared each group regarding intraoperative fluid balance, hypovolemia and perioperative complications. In the 3rd or 4th operation, mean blood loss and fluid administration were more than those of the 1st or 2nd operation. Respiratory dysfunctions or circulatory complications such as hypotension, oliguria occurred more frequently during or after the 3rd or 4th operation. Since patients are in hyperdynamic and hypercatabolic state at the time of the 3rd or 4th operation patients, they will be easily damaged in the peri-operative period. This study suggests that we should bear in mind, in the anesthetic management of burned patients, that they can be in hyperdynamic state as well as in shock state. PMID- 8366564 TI - [Monitoring of peripheral tissue oxygenation with near infrared spectrophotometry during abdominal or iliac aortic cross-clamping surgery]. AB - Peripheral tissue oxygenation was monitored with near infrared spectrophotometry during abdominal or common iliac aortic cross-clamping surgery. Six patients who had abdominal aortic aneurysm (AAA) and eight patients who had aortic sclerotic occlusive disease (ASO) were studied. At the beginning of cross-clamping, oxyhemoglobin was decreasing and deoxyhemoglobin was increasing in all AAA patients. Average of 37 minutes following cross-clamping of abdominal aorta, both hemoglobin values were stabilized. On the other hand, changes in both hemoglobin values were delayed or missing in ASO patients. The results suggest that the duration from cross-clamping to stabilization is related to co-lateral blood flow. During operation, monitoring of peripheral blood flow with near infrared spectrophotometry is useful for detection of peripheral ischemia and for the estimation of postoperative local blood flow. PMID- 8366566 TI - [Anesthetic management of a patient with HELLP syndrome with bronchial asthma]. AB - We gave anesthesia for cesarean section to 30 year-old female with HELLP syndrome with bronchial asthma. HELLP syndrome is characterized by hemolysis, liver dysfunction and thrombocytopenia, besides syndrome of severe toxemia of pregnancy. After intubation with sevoflurane, diazepam and vecuronium, anesthesia was maintained with nitrous oxide, oxygen, sevoflurane and vecuronium, because she had an attack of bronchial asthma before operation. Though she had no eclampsia nor hypertension during operation, her babies were intubated and were cared in pediatric ward. Though she had improvements of liver dysfunction and thrombocytopenia after operation, it took 2 days to extubated, because she had frequent attacks of bronchial asthma. We conclude that we should perform cesarean section for a patient with HELLP syndrome as soon as possible. PMID- 8366565 TI - [Anesthetic management of a patient with pemphigoid for prosthetic replacement after femoral neck fracture]. AB - We report an 83 year-old male with pemphigoid who underwent replacement of a femoral neck prosthesis following femoral neck fracture. Problems associated with anesthetic management of patients with vesiculobullous diseases such as pemphigoid include fluid, electrolyte and protein loss, and secondary infection because of the fragility of the skin and mucous membranes. Avoidance of trauma to the skin and mucous membranes is therefore important. Intubation of the trachea may be hazardous because of the possibility of airway obstruction resulting from oropharyngeal and laryngeal bullae. The patient was successfully anesthetized with spinal anesthesia using 2.5 ml of tetracaine in a 0.4% solution of 0.45% NaCl. An evacutable mattress was used to protect the patient from pressure points in the lateral position, and to minimize the hazards from pressure by spreading the weight. Surgery proceeded uneventfully and the postoperative period was uncomplicated. PMID- 8366567 TI - [Anesthetic consideration of a patient with congenital insensitivity to pain with anhidrosis]. AB - Congenital insensitivity to pain with anhidrosis is a rare disorder but several clinical anesthetic experiences have been reported in Japan. We anesthetized a patient with this disorder for orthopedic operation with a low concentration of sevoflurane under monitoring of body temperature and we measured the concentrations of plasma ADH, cortisol and catecholamines levels before, during and after the operation. There were no problems during anesthesia and the patient awoke rapidly. ADH, cortisol and epinephrine concentrations showed slight elevations during and after the operation. The management of intraoperative body temperature and the necessary level of anesthesia were also discussed. PMID- 8366568 TI - [An analysis of the status of surgical transfusion and a trial of maximum surgical blood order schedule (MSBOS) in Fukui Medical School Hospital]. AB - To evaluate the present status of surgical transfusion during operations, we computed the amount of preoperative preparation and intraoperative use of blood. And we examined cross-match to transfusion ratio (C/T ratio) and maximum surgical blood order schedule (MSBOS) based on the statistical data in our hospital. The result revealed that too much blood was prepared in our hospital. The amount of prepared blood was 12,825 units of which 2,419 units were transfused (1 unit = 200 ml of whole blood). The mean C/T ratio was 5.30. And a trial of MSBOS revealed that we could save 70% of the blood presently prepared. We are sure that the introduction of T & S and MSBOS will lead to more efficient transfusion in our hospital. PMID- 8366569 TI - [Development of an anesthesia ledger using relational database]. AB - An anesthesia ledger was developed using relational database KIRI Ver3. This anesthesia database includes 33 items for input, for example patient's name, patient's I.D. number, data of operation, diagnosis, operative procedure, name of surgeon, name of anesthesiologists and so on. One can select data from displayed menu cards only by rolling down or rolling up the cursor at 19 items and can input numbers by keyboard at twelve items. Even a computer beginner can easily operate it after a minimal training. Only patient's name must be input by text style. We can construct this anesthesia database only by use of functions of KIRI Ver3 without programming. One can use this anesthesia ledger at any operative facilities by changing a part of database and a file of doctor's name. PMID- 8366570 TI - [In vitro production of gamma/delta T cell clones and their characteristics]. AB - Human TCR gamma/delta cell clones were produced from both CD2-depleted normal peripheral blood mononuclear cells (PBMC) and leukemia and lymphoma cell predominant PBMC, effusion cells and lymph node cells in in vitro cultures with rIL-1 and rIL-2 and using limiting dilution techniques. These clones were then analyzed as to their cell morphology, phenotype and non-major histocompatibility restricted cytotoxicity (NMRC) to K562. The results of the cloning from CD2 depleted PBMC showed 112 WT31+ gamma/delta-1- clones, 62 WT31- gamma/delta-1+ clones and 101 WT31- gamma/delta-1- clones. These were produced in 17 serial experiments. The addition of EBV-infected B cell line cells as feeder cells resulted in better production of gamma/delta-1+ and non-T cell clones than that of WT31+ clones. One typical example of the cloning from lymphoblastic lymphoma cell-predominant PBMC resulted in the production of 8 gamma/delta-1+ and 3 WT31+ clones. Most of the clones proven to be gamma/delta-1+ clones had the CD2+ CD3+ CD4(-)-+ CD8(-)-+ TCR delta-1+ beta F1- alpha F1- and delta TCS-1- phenotype, but few clones displayed CD2- or delta TCS-1+ phenotype. These gamma/delta-1+ clones were morphologically large granular lymphocytes, but functionally they did not have NMRC to K562. It is possible to say that TCR gamma/delta clones were rather easily produced from TCR alpha/beta cell-depleted PBMC and effusion cells, and can be used for the study of their nature and characteristics. PMID- 8366571 TI - [A comparative study of VEPA and ACOMEP-BD regimen for the patients with non Hodgkin's lymphoma]. AB - Between 1981 and 1990, ACOMEP-BD regimen (adriamycin, cyclophosphamide, vincristine, methotrexate, etoposide, prednisolone, bleomycin, dacarbazine) was compared with VEPA regimen (vincristine, cyclophosphamide, prednisolone, adriamycin) in 66 newly diagnosed patients younger than 65 of age, with non Hodgkin's lymphoma (NHL). The median age of the patients was 47.5 years (range 22 64 years), 43 males and 23 females. One patients were in stage I, 6 were in II, 27 were in III, 32 were in IV. Twenty-seven patients received VEPA and 39 received ACOMEP-BD. The therapeutic results of 66 patients with ACOMEP-BD or VEPA were as follows: complete remission (CR) rate of 54% and 48%; relapse rate of 29% and 77%; CR duration of 2-34 months (mean: 22 months) and 2-74 months (16 months); freedom-from-relapse survival (at 3 years) of 71% and 38%; and overall survival (at 4 years) of 62% and 26%, respectively. In these results, only relapse rate was significant and the others were not. Prognostic factors were performance status (PS) and lactate dehydrogenase level for ACOMEP-BD, and PS and marrow involvement for VEPA. Received dose intensity was 0.85 in ACOMP-BD and 0.41 in VEPA. It was expected that outcome of patients with NHL can be improved by increasing dose intensity. PMID- 8366573 TI - [Refractory bilateral pneumothoraces complicated with interstitial pneumonitis after bone marrow transplantation]. AB - We report here a case of 33 year-old-man with refractory bilateral pneumothoraces during the treatment for interstitial pneumonitis 6 months after bone marrow transplantation (BMT). He was diagnosed as having acute myelogenous leukemia (AML) M1. He was treated with chemotherapy, and cerebral irradiation. BMT was performed in August 1989 from a sibling donor whose human leukocyte antigen was matched, ABO blood type mismatched. Preconditioning regimen was cyclophosphamide and total body irradiation (TBI). BMT was successful without major graft versus host disease. Thereafter he complained of respiratory symptom and was admitted on June 14 1990. Computed tomogram (CT) scan showed interstitial and alveolar shadows. We started the treatment against bacterial infection, Pneumocystis carinii, cytomegalovirus (CMV) and against interstitial pneumonitis with bolus dose of steroid. The transbronchial lung biopsy specimen revealed interstitial pneumonitis without typical CMV nor pneumocystis carinii pneumonia. Although a CT scan showed improvement of pneumonitis, bilateral pneumothoraces occurred. The adhesion therapy became successful after the reduction of steroid dosage. A pneumothorax rarely occurs after BMT. In this case it is speculated that TBI might be responsible for interstitial pneumonitis, and the steroid might have inhibited the adhesion therapy of pneumothorax. PMID- 8366572 TI - [Treatment and prognosis after late relapse in childhood acute lymphoblastic leukemia]. AB - We evaluated the clinical courses and laboratory features in 13 late-relapse cases of 55 children with acute lymphoblastic leukemia who had been in complete remission for longer than their years. In 8 of 13 cases, leukemia relapsed in bone marrow; 2 with testicular, 1 with central nervous system and one with ovarian involvement. Further, extramedullary relapse not involving bone marrow occurred in 5 cases (4 testicular and 1 CNS). Late-relapse was more frequently observed in boys (37.5%) than in girls (4.4%). Initial age and leukocyte counts were of no value in predicting late-relapse. The relapse rate in cases initially treated by the VPL regimen was twice that of those by a multi-drug regimen. A second prolonged remission was achieved in 5 of 10 cases by combinations of intensive chemotherapy (modified HEX) and irradiation to the testes or CNS. On the contrary, all late relapse patients initially treated by the multi-drug chemotherapy had a poor outcome. More intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, should be employed in this group of patients. PMID- 8366575 TI - [Spontaneous remission in adult T-cell leukemia]. AB - Spontaneous remission in a 50-year-old woman with adult T-cell leukemia (ATL) is presented. The patient was referred to our hospital because of generalized lymphadenopathy and the appearance of abnormal lymphocytes with convoluted nuclei in the peripheral blood. She was diagnosed as ATL because of the characteristic morphological ATL cells, cell surface marker analysis and the presence of serum antibody to human T-cell lymphotropic virus type-I (HTLV-I). However during the following weeks before admission, her leukocyte count and ATL cells in the peripheral blood decreased in number even though she received no therapy. After admission, abnormal lymphocytes in the peripheral blood disappeared and lymphadenopathy decreased in size, LDH level was normalized. Spontaneous remission had continued ten months without chemotherapy, but she developed recurrence thereafter and died two years later after onset with progressive disease. Gene analysis study by Southern blot analysis showed monoclonal integration of HTLV-I proviral DNA at the same positions both before regression and after recurrence. In this case, the trigger of spontaneous remission was unclear. PMID- 8366574 TI - [Parapsoriasis en plaque suspected of progression to mycosis fungoides associated with extranodal malignant B cell lymphoma of the cheek]. AB - A 59-year-old female, clinically diagnosed as having parapsoriasis en plaque for ten years, was referred on June 1991 to the Department of Oral Surgery in the Dental School of showa University with a complaint of painless swelling of the left malar area. The swelling was found to have been caused by a tumor. Since the excised tumor was suspected to be a malignant lymphoma, she was admitted to our hospital. The specimen was subsequently confirmed to be a malignant lymphoma of the diffuse large cell type according to the LSG classification, and was immunologically confirmed to be a B cell lymphoma. In addition, the excised skin was suspected of incipient mycosis fungoides. She was classified as having stage IE disease according to her bone marrow biopsy and other examinations. she was treated with combination of chemotherapy (CHOP) and radiation therapy. This subject was interesting because her tumor probably resulted from a parapsoriasis en plaque skin lesion. PMID- 8366576 TI - [Partial and complete disappearance of Ph1 chromosome in two patients with chronic myelogenous leukemia after conventional chemotherapy]. AB - [Case 1] A 44-year-old female was referred to our hospital because of leukocytosis. The WBC count was 26400/microliters and NAP score 21. As Ph1 chromosome was detected, she was diagnosed as CML and treated with busulfan. Because of the rapid decrease of WBC, we stopped busulfan. Progressive pancytopenia and an increase of myeloblasts and promyeloblasts in the bone marrow was observed. We started vincristine and prednisolone therapy. Ph1 chromosome was not detectable and southern blot analysis did not show rearranged bands of M-bcr three years after the last therapy. [Case 2] A 74-year-old female was referred to our hospital by reason of leukocytosis and thrombocytosis. The WBC count was 22,500/microliters, the platelet 907,000/microliters, NAP score 53, and Ph1 chromosome was found. The diagnosis of CML was made, and she was treated with busulfan. The WBC rapidly fell to 1,900/microliters, when chromosome analysis revealed the presence of Ph1 negative clones (4/20). She was admitted due to thrombocytopenia and leukocytosis with the additional chromosome change of i (17q). Her peripheral blood and bone marrow pictures were consistent with blast crisis, and she died of cardiac tamponade. These two cases show the heterogeneity of CML patients, and also suggest the possibility that keeping the WBC count low may lead to a decrease of Ph1 positive clones. PMID- 8366577 TI - [A case of chronic neutrophilic leukemia associated with polycythemia vera]. AB - A 74-year-old male patient was seen on December 15, 1980 because of right shoulder pain and leukocytosis. The spleen and the liver were enlarged, and palpable, 3 and 4 fingerbreadths below the costal margin respectively. The red blood cell count (RBC) was 899 x 10(4)/microliters, hemoglobin (Hb) 20.6 g/dl, reticlocyte (Ret) 7/1000, platelets (Plt) 34.2 x 10(4)/microliters, the white blood cell count (WBC) 26,800/microliters with 86% neutrophils. A bone marrow aspiration showed the nucleated cell count (NCC) to be 16.5 x 10(4)/microliters, and the myeloid/erythroid ratio (M/E) 2.0. The patient was treated with venesection and later with carboquone. Since September 1990 he has not been treated with any agents because of erythrocytopenia. In July 25, 1991, the spleen was enlarged, and palpated 8 fingerbreadths below the costal margin. The RBC was 456 x 10(4)/microliters, Hb 12.5 g/dl, Ret 9/1000, Plt24.2 x 10(4)/microliters, the WBC41,500/microliters with 90% neutrophils. Bone marrow aspiration showed the NCC to be 16.5 x 10(4)/microliters, M/E14.3, with no atypical cells. Chromosome studies of marrow cells revealed no Ph1 chromosome. Many hematologic malignancies have been occasionally associated with polycythemia vera (PV), but chronic neutrophilic leukemia associated with PV is a very rare condition. PMID- 8366578 TI - [Successful treatment with deferoxamine in a case of refractory anemia]. AB - A 60-year-old female was admitted to our hospital because of macrocytic anemia with anisopoikilocytosis and thrombocytopenia. A bone marrow aspiration revealed hypolasia with nuclear deformity of neutrophils and decrease of megakaryocytic numbers. Karyotype analysis showed 47, XX, +8. A diagnosis of refractory anemia was made. The patient was treated with metenolone acetate without clinical response. Deferoxamine (2g/day) was given intravenously by continuous infusion. Ten days after deferoxamine treatment, the levels of RBC and platelet increased and the effect lasted 100 days after discontinuance of deferoxamine. Bone marrow aspiration showed normoplasia with normal megakaryocytes numbers. However, anisopoikilocytosis, abnormality of MCH and MCHC, and karyotype abnormality similar to the first medical examination remained. These data might suggest that deferoxamine induced differentiation of abnormal hemopoietic cells in refractory anemia. Retrobulbar neuritis which developed 30 days after initiation of treatment disappeared after halting deferoxamine treatment. PMID- 8366579 TI - [Detection of erythropoietic inhibitor factor in a case of acute non-lymphocytic leukemia after allogenic bone marrow transplantation]. AB - A 36-year-old man was diagnosed as having acute non-lymphocytic leukemia (AML M5b) in 1985 and received allogenic bone marrow transplantation from an ABO mismatched sibling in January 1987. Recovery of erythropoiesis in this patient was delayed, then the hemoglobin level improved in parallel with disappearance of anti-A antibody in the serum on day 260 post transplantation. However, as anemia occurred again despite no relapse of leukemia on day 350, we tried to determine the presence of erythropoietic inhibitory factor in this patients. Erythroid colony formation was decreased when bone marrow cells were co-cultured with peripheral mononuclear cells from the patient. Further, erythroid colony inhibitory activity was found in conditioned medium of PHA-stimulated T cells from the patient. Sephadex gel fractionation showed that the molecular weight of this inhibitory factor was approximately 11,000 and addition of a high concentration of EPO did not eliminate the inhibitory activity. These findings suggest that the novel inhibitor described in this manuscript, produced by T cells, was differed from previously reported inhibitors such as anti-EPO antibody, spermine and uremic toxins. PMID- 8366580 TI - [Common acute lymphoblastic leukemia showing hypo-gamma-globulinemia and cerebral infarction due to cerebral artery obstruction]. AB - A patient who developed hypo-gamma-globulinemia and cerebral infarction during the treatment for acute lymphoblastic leukemia (ALL) is reported. In this patient fever and rash during radio-therapy for central nervous system (CNS) prophylaxis and nausea and vomiting were observed during maintenance therapy. On the laboratory findings high level of the protein level in the cerebrospinal fluid and the eosinophil count of the peripheral blood were found in every examination. We attempted to isolate various viruses in consideration of the possibility of infection, but no virus could be detected. The effects of methotrexate (MTX) and l-asparaginase were also suspected. Since nausea and vomiting disappeared after discontinuation of MTX administration, the drug may had some effect, and the possibility of cerebral damage by MTX can not be excluded. Complication of irradiation are reported to occur often more than 10 years after the treatment, but this patient had the onset only 2 years after the treatment. Therefore, irradiation was unlikely to be responsible for the symptoms. The relation between the hypo-gamma-globulinemia and cerebral infarction was also unknown. PMID- 8366581 TI - [A giant esophageal ulcer in a hemophiliac with HIV infection]. AB - A 21-year-old man with hemophilia B and human immunodeficiency virus (HIV) infection was admitted with hematemesis and melena. After admission, esophagogram and endoscopy showed a single giant ulcer with ovoid shape and slightly irregular margins in the middle esophagus. Biopsy specimens of the esophageal ulcer showed non-specific granulation and etiology was unknown. Therapeutic trails of famotidine, sodium alginate, acyclovir, and amphotericin B did not result in favorable response. With a combination therapy of dexamethasone and sucralfate, the swallowing pain was rapidly disappeared with gradual improvement of the ulcer. To our knowledge, this is the first report of a giant esophageal ulcer in a HIV infected patient in Japan. PMID- 8366582 TI - [Prostaglandin E1 bladder instillations for a patient with severe hemorrhagic cystitis after allogeneic bone marrow transplantation]. AB - A 39-year-old female with AML (M2) underwent allogeneic bone marrow transplantation (BMT) on July 8th, 1991. The post transplantation course had been going well until day 85 post BMT, when severe hemorrhagic cystitis with right hydronephrosis and ureter stenosis developed. Adenovirus type 11 was isolated from the urine. She received instillations of prostaglandin E1 (PGE1) directly into the bladder after the appearance of clots in the urine. Complete resolution of hematuria was obtained by two courses of this treatment. PGE1 bladder instillations seem to be effective for the control of hematuria caused by severe hemorrhagic cystitis after BMT. PMID- 8366583 TI - [Definition, classification and clinical symptoms of cholelithiasis]. AB - Generally, the cases with symptomatic biliary stone are diagnosed as cholelithiasis and asymptomatic cases are not defined as cholelithiasis in the strict sense. However, asymptomatic stones are often diagnosed and treated as cholelithiasis. In the diagnosis and treatment of cholelithiasis, it is important to study the localization and classification of biliary stones relation to clinical symptoms. PMID- 8366584 TI - [Pathogenesis and animal model of gallstone disease]. AB - Both cholesterol and pigment gallstones are multifactorial diseases. The broad outlines of the mechanism and limit of cholesterol solubilization in bile are well-understood, whereas the physical-chemical solubilities of unconjugated bilirubin and other calcium salts remain unclear. The importance of crystallization kinetics in gallstone formation is also well-recognized and several protein determinants of such process have been reported in bile. The chances of crystal growth and stone formation are further enhanced by mucus hypersecretion and gallbladder hypomotility. The use of animal models will continue to be useful not only in promoting our understanding of the pathogenesis but also in developing new chemicals for dissolution and prevention of gallstone diseases. PMID- 8366585 TI - [Gallstone classification and analysis of their constituents]. AB - Macroscopic classification of gallstones as proposed by the Japanese Society of Gastroenterology is based on the presence of characteristic structures on the cut surface. According to this classification, gallstones can be broadly divided into three types: cholesterol gallstones, pigment gallstones and rare gallstones. This classification is widely accepted in Japan because of its clinical applicability. A more accurate classification requires analysis of the constituents of gallstone. In particular, infrared absorption spectroscopy has been utilized for this purpose because it enables a rapid and easy analysis, requiring only small amounts of sample. In the selection of patients with gallstones for non-surgical treatment, such as ESWL and dissolution therapy, qualitative diagnosis is necessary. With this in mind, we have attempted to produce CT-Profile curves of individual gallstones, depicting changes in CT values assessed along cross sectional lines passing from the center of the stone to their maximum diameters. This method allowed qualitative diagnosis almost of all gallstones. PMID- 8366586 TI - [Trace metal elements in gallstones and their roles]. AB - The concentrations of metal elements in gallstones were measured by absorption spectrometry. Crystallographic analysis by the powder X-ray diffraction method was also performed. For all stones calcium was the major component. In calcium carbonate stones aragonite form, one of the CaCO3 polymorphs and usually unstable in nature, was dominant. As a whole, black-stones contained highest proportions of all metal elements. But these stones were crystallographically grouped into three types; they are calcium carbonate-, calcium phosphate-, and other-one. In each type, the concentration of metal element differed greatly. It is suggested that in black-stones the amount of Mn is remarkable and Cu is highly correlated to black residue. It was true, but Mn was remarkable especially in calcium phosphate-type and Cu was the highest in other-type. PMID- 8366587 TI - [Etiology of cholelithiasis]. AB - The incidence of gallstone has been gradually increased in the last few decades in Japan and the recent study revealed that approximately 15% of the autopsy cases had biliary stones. In the last 25 year interval, the nature of gallstones was greatly changed. In detail, the incidences of cholesterol gallstone and black stone were increased from 46.7% to 66.9% and from 0.8% to 12.1%, respectively, whereas that of calcium bilirubinate stone was decreased from 41.5% to 21.0% of the whole cholelithiasis cases. The factors influencing these changes were probably due to recent increase of fat diet intake and decrease of ascariasis by improvement of environmental hygiene. However, the factors that caused the change in black stone has not been defined. PMID- 8366588 TI - [Natural course of asymptomatic gallstone disease]. AB - Of 1850 patients with cholelithiasis diagnosed in the past 17 years, 1116 female and 734 male, 598 patients (32.3%) presented with one or more of three major symptoms, i.e., abdominal pain, fever and jaundice, whereas the remainder (67.7%) had none of these symptoms. The proportion of the asymptomatic patients was similar in all age groups, being around 70%. Only 20 per cent of 680 asymptomatic patients, followed for 10 to 17 years (median 13.3 years), developed biliary symptoms. Older patients over 70 years of age had a higher rate of change to the symptomatic group, as compared with younger patients under 70, 29.5% vs. 19.3%, respectively. During this period, carcinoma of the gallbladder developed in one of the asymptomatic patients (0.1%). Oral dissolution therapy was successful in only 4.2 per cent of attempted cases and associated with a recurrence rate of as high as 20%. We conclude that asymptomatic gallstone patients should only be followed up by ultrasound twice a year without any treatment. PMID- 8366589 TI - [Diseases with high incidence of gallstone complication]. AB - Gallstones are often complicated with diseases such as liver cirrhosis, hemolytic anemia, post-valvular replacement, post-gastrectomy, biliary tract cancers, diabetes mellitus, and during clofibrate therapy. The frequency of gallstones, types of stones and their pathogenesis in these situations are discussed in this chapter. In liver cirrhosis, hemolytic anemia and post-valvular replacement, black stone formation is enhanced due to bilirubin over-production, caused mainly by hemolysis. Bilirubin stone formation is accelerated gastrectomy and by biliary tract cancer, because of the decrease in gallbladder contraction, cholestasis and bacterial infection, etc. The incidence of cholesterol gallstone is high in patients with diabetes mellitus and with clofibrate therapy. PMID- 8366590 TI - [Diagnosis of cholelithiasis]. AB - Evaluation of the patient with suspected cholelithiasis has been changed dramatically recently, to make accurate prediction of composition of the gallstone. That is mainly because of improvement and development of all kinds of diagnostic imaging modalities and development of several nonsurgical options. If we do the initial evaluation of the patient, it is natural to choose the ultrasonography first, because of its easiness and noninvasiveness. But it is important to choose the most appropriate modality following ultrasonography, in order to complete the integrated imaging diagnosis. Here we describe the gross feature of the each modality, and how we choose it in order to make accurate diagnosis and to arrive at a treatment plan best suited for each patient. PMID- 8366591 TI - [Diagnostic methods of gallstones--plain radiogram and contrast examination of biliary system]. AB - There is a wide spectrum of diagnostic imaging modalities to evaluate the biliary system, such as plain radiogram, echogram (US), oral cholecystogram (OCG), intravenous cholangiogram (DIC), CT, MRI, and RI scintigram. Since the late 1970's US, non-invasive and easily available, is the first choice of examination when gallstones are suspected because of achievement of detailed resolution. OCG or DIC is rarely performed for gallstones. However, it was not until the advent of various measures of treatment for gallstones, other than cholecystectomy, such as dissolution therapy or extracorporal shock wave lithotripsy of gallstones, that contrast examination of the biliary system has been re-utilized to evaluate the characteristics, number and size of gallstones, and patency of cystic duct, which are important data. The indications and significance of plain and contrast examinations for gallstone disease is discussed. PMID- 8366592 TI - [Diagnosis of cholelithiasis--endoscopic pancreatocholangiography]. AB - Endoscopic cholangiography is fundamentally evaluated as X-ray anatomy of the biliary system as well as the principal technique for endoscopic treatments that is endoscopic papillotomy and endoscopic drainage, while gallstone is routinely diagnosed by ultrasonography in medical practice. By endoscopic cholangiography, stones in the cystic duct and the common bile duct are confirmedly diagnosed in the same quality as gallbladder stones, and the anatomical information of the cystic duct, the gallbladder, and the duodenal papilla are clearly demonstrated, which are required in many therapeutic procedures for gallstones diseases including laparoscopic cholecystectomy. PMID- 8366593 TI - [Ultrasonography in cholelithiasis]. AB - Ultrasonography has become the first line examination in the diagnosis of cholelithiasis. As for the gallbladder, extracorporeal ultrasonography is the most useful and the safest procedure. Ultrasonic properties of gallstones even suggest the feasibility of dissolution therapy. The detectability of choledocholithiasis is, however, not satisfactory. This deficiency has been overcome by combining endoscopy with ultrasound. Endoscopic ultrasonography, as well as ERCP, is a useful tool for examining the extrahepatic bile duct and the pancrease. Recently, with the development of laparoscopic cholecystectomy, intraoperative ultrasonography during laparoscopic surgery has considerably improved with introduction of new probes and may replace most of the methods of intraoperative cholangiography in the future. PMID- 8366594 TI - [Diagnostic imaging of cholelithiasis--CT & MRI]. AB - CT and MRI are inferior to ultrasound for detection of gallstones. CT and MRI however, might have distinctive features for diagnostic imaging of the cholelithiasis. The CT is sensitive, as regard with calcification of the gallstones, and able us to diagnose the composition of the gallstones manipulate the CT number. Then spiral CT, which is a new technique, is expected to improve the accuracy of detection of gallstones. Three-dimensional CT reconstruction images are useful in the sense of the anatomy of the biliary system. MRI is superior to evaluate bile juice concentration, so that it appears to make it possible to evaluate gallbladder function. Furthermore, the MRI has the potential advantage for acquisition the new knowledge relating to stone lysis. PMID- 8366595 TI - [Rationales for the selection of the therapies for gallstones]. AB - Surgical cholecystectomy used to be the only definitive method of gallstone treatment. Recently, however, there have been greatly advancing in the therapies for gallstones, which comprise oral or topical litholysis, lithotripsies with shock wave or endoscopical techniques, and laparoscopical cholecystectomy. Some factors must be considered in selecting the method for the treatment of gallstones, such as; well-understanding of the physiology and the pathophysiology of gallbladder (stones), precise US tomography, the effects of diet, and especially the patient's performance status, patient's profile and informed consent. PMID- 8366596 TI - [Per oral gallstone dissolution therapy]. AB - In this paper the author describe present status and problems of Per oral cholesterol gallstone dissolution therapy by bile acid. 1) Both ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) decrease the cholesterol output in bile, but their action mechanism somewhat differs. 2) Clinical results of UDCA treatment in our hospital during past 17 years are as follows. Complete dissolution rate Approx. 20% Partial dissolution rate Approx. 20% 3) In the attempt to increase the complete dissolution rate, bedtime administration method (one time administration instead of 3 times, every day), combination therapy of UDCA and CDCA and UDCA plus simvastatin (HMG-CoA reductase inhibitor) were tried. The results of these trial were not superior compared with ordinary UDCA therapy (3 times after each meal administration). 4) The author concluded from the results that small size (< 1 cm in diameter), Ia in ultrasonographic classification, floating by oral cholecystography, and radiolucent gallstones are the most suited for bile acid dissolution therapy. PMID- 8366597 TI - [Direct gallstone dissolution therapy with GS-100]. AB - We have developed GS-100, a new direct dissolving drug with strong dissolution property for cholesterol stone by supplementing d-limonene, a dissolvent used since 1974, with 30% medium-chain monoglyceride (MCM). The new drug was applied in 23 patients with gallbladder stones and three with bile duct stone. The presumptive analysis of the composition of the stones was drawn from the CT recordings. As non-invasive therapies, methyl tert-butyl ether (MTBE) dissolution and extracorporeal shock wave lithotripsy (ESWL), which are commonly used in Europe and America, have been reported as being favourable; however, GS-100 is superior in respect to safety and applicative dimension, suggesting of the possibility of using GS-100 as an important drug in the non-invasive therapy for gallstone in the near future. PMID- 8366598 TI - [Extracorporeal shock wave lithotripsy]. AB - Extracorporeal shock wave lithotripsy (ESWL) was performed in 84 patients with gallbladder stones. The gallstones completely disappeared within 12 months after ESWL, in 31% of the patients with one to three radiolucent stones not larger than 3 cm in diameter and in 57% of the patients with a solitary stone up to 2 cm with the ultrasonographic gallstone pattern of I a or I b. There was no major complication. ESWL is a safe and effective treatment in selected patients with a solitary radiolucent stone not larger than 2 cm with I a or I b pattern. PMID- 8366599 TI - [Percutaneous transhepatic cholangioscopic lithotripsy]. AB - With an advent of cholangiofiberscope in 1975, tremendous changes have been made in thinking way on the treatment of biliary tract stones. The technique of percutaneous transhepatic cholangioscopy (PTCS) was detailed and its clinical significance was discussed in this paper. PTCS is the technique which is conducted by insertion of cholangiofiberscope into the biliary tract through the dilated fistula produced by percutaneous transhepatic biliary drainage (PTBD). Advantages of this techniques are; (1) it is applicable to the cases who had had bilio-enteric anastomosis or gastro-jejunostomy before, (2) it can be repeatedly carried out if the fistula is maintained open, (3) stones visible are readily removable with the instruments guided by cholangiofiberscope and finally, (4) the informations necessary to select an adequate surgical procedure can be obtained by PTCS, because biliary architecture is clearly delineated. For the period of 18 years started from 1975, 126 cases with intrahepatic stones have been encountered in our Hospital, endoscopic stones extraction technique was successful in 106 out of 121 cases excluding 5 cases converted for hepatic lobectomy. And the prognosis of the cases in which stones were successfully extracted were, in general, good. Therefore, the authors believe that the therapeutic results would be significantly improved with the routine use of PTCS. PMID- 8366600 TI - [Percutaneous transhepatic cholecystoscopic lithotomy (PTCCSL)]. AB - We have performed percutaneous transhepatic cholecystoscopic lithotomy (PTCCSL) in 37 cases of cholecystolithiasis and have succeeded in the removal of the stones in all cases without any serious complications. The average period from gallbladder puncture until the completion of lithotomy was 11.8 days and PTCCSL was performed an average of 2.1 times. The follow-up period after lithotomy ranged from one to 60 months, with an average of 24.7 months. Gallbladder function returned to the pretreatment level. However, gallstones recurred in 7 cases (18.9%). In comparison with both cholecystectomy by laparotomy and laparoscopic cholecystectomy, PTCCSL is less invasive, but recurrence may occur in a relatively short period with PTCCSL. Therefore PTCCSL is particularly indicated for high-risk patients who cannot undergo general anesthesia. PMID- 8366601 TI - [Endoscopic sphincterotomy for lithotripsy (EST-L) of bile duct stones]. AB - We performed EST-L for 555 patients with choledocholithiasis between 1981 and 1992. With the aid of conventional occlusion balloons and dormia-type baskets, calculi < or = 1.5 cm was extracted with relative ease. In patients with larger stone (> 1.5 cm), the mechanical lithotripter, extracorporeal shock wave lithotripsy (ESWL) and electrohydrolic lithotripsy were used for the lithotripsy. The overall success rate was 95%. Important early and late complications from these procedures occurred in 6.9% and 9.1% of all cases respectively. This result reveal that EST-L is safe and effective therapeutic procedures for choledocholithiasis. We would recommend EST-L is adopted as an initial measure to remove common bile duct stones. PMID- 8366602 TI - [Treatment of common bile duct stones by peroral cholangioscopy]. AB - Endoscopic papillotomy (EPT) has become a popular form of treatment in managing common bile duct stones. But it may fail in difficult cases such as large stones of over 20 mm, confluence stones, and impacted stones. Over the past 5 years, our success rate in clearing the bile duct by conventional endoscopic techniques (mechanical lithotripsy) was about 90 per cent. Recently, we have performed electrohydraulic lithotripsy or laser lithotripsy with peroral cholangioscopy in these difficult cases. Complete clearance of the duct was obtained in all 23 patients who underwent peroral cholangioscopic lithotripsy. No complication occurred. In conclusion, peroral endoscopic treatment of common bile duct stones should be safe and effective. PMID- 8366603 TI - [The indications and results of laparoscopic cholecystectomy]. AB - Laparoscopic cholecystectomy was successfully achieved in 93% of the patients, who required removal of the gallbladder, in our institution. Other reports have also shown that more than 90% of patients who required cholecystectomy, were candidates for laparoscopic cholecystectomy. Serious complications occurred in 2.1% of our series and in 2-4% of the literature. The complications included bile duct injury (around 0.5%) and visceral injury (0.2-0.4%). The incidence of complications resulting from technical failure seems to be higher in laparoscopic cholecystectomy than in conventional cholecystectomy but is acceptable for initial experience. Laparoscopic cholecystectomy will become the standard therapy of gallstone for its effectiveness and less invasiveness. PMID- 8366604 TI - [Cholecystectomy followed by one inch minilaparotomy]. AB - A new surgical treatment for cholelithiasis was developed. This procedure is performed by a 2-3 cm subcostal skin incision in the right hypochondrium. About 400 patients were treated by this technique. This procedure is not different in terms of blood loss or operation time compared to conventional methods, and no significant complications have occurred. Intraoperative examination is performed routinely because of easy insertion of a tube from the cystic duct into the bile duct. Minimization of the length of the incision facilitates postoperative recovery greatly, shortening the hospital length-of-stay within 3 days. These principles allowed even patients with choledocholithiasis to undergo a minilaparotomy and be discharged within 1 week. PMID- 8366605 TI - [Traditional open cholecystectomy]. AB - During the past 5 years, traditional open cholecystectomy was performed on 344 patients with gallbladder stones at our hospital. Using the data obtained, we studied the indications and results of traditional open cholecystectomy. In the cases of gallbladder stones with a history of cholecystitis, cholecystectomy was performed as a rule by laparoscopic cholecystectomy. However, traditional open cholecystectomy was chosen in cases which were complicated by perforation, pericholecystic abscess, internal biliary fistra, cirrhosis, or suspicious carcinoma of gallbladder. Investigation of the time of operation revealed that early operation tended to be performed easily. However, cases with gallbladder stones were often complicated with carcinoma of alimentary tracts, therefore before operation we must examine the alimentary tract. Cases in which gallbladder could not be visualized under ERCP, and those accompanied by pericholecystic abscess under US were difficult to operate on by laparoscopic cholecystectomy. Thus many cases required laparotomy. Postoperative complications of open cholecystectomy were rare, it was concluded that traditional cholecystectomy is one of the most valuable procedures for the treatment of gallbladder stones. PMID- 8366606 TI - [Non-surgical biliary drainage for cholelithiasis]. AB - Non-operative methods to treat obstructive jaundice and cholangitis caused by cholelithiasis are endoscopic and percutaneous biliary drainage. Usually, endoscopic papillotomy and stone removal by basket catheter is available for treating choledocholithiasis. It is necessary to place a drainage catheter into the bile duct in patients who have severe cholangitis or remaining stones. On the other hand, percutaneous biliary drainage is useful in case of emergency and in patients reconstructed by the Billroth II method. Biliary drainage is necessary to treat severe cholangitis as soon as possible, for it sometimes causes endotoxin shock, disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). PMID- 8366607 TI - [Treatment of intrahepatic gallstone]. AB - The postoperative outcomes in patients with hepatolithiasis are greatly affected by the presence of residual stones. One hundred and seventeen patients with hepatolithiasis treated in our clinic were analysed. The indication of hepatectomy for hepatolithiasis was determined by the degree of stricture of intrahepatic bile duct. The rate of residual stones was reduced from 54.5% to 14.5% by the introduction of choledochoscopical lithotomy. Thus, pre- and postoperative choledochoscopical examination and lithotomy are shown to play an important role in treatment of the patients with hepatolithiasis. PMID- 8366609 TI - [Current therapy of obstructive jaundice due to cholelithiasis]. AB - On recent development of apparatus and techniques of ultrasonography and endoscopy we prefer to try the following procedures for removing jaundice instead of surgical operation: 1) Percutaneous Transhepatic Biliary Drainage (PTBD) 2) Endoscopic Retrograde Biliary Drainage (ERBD) 3) Endoscopic Naso-Biliary Drainage (ENBD) 4) Endoscopic Sphincterotomy (EST). After removing the jaundice and inflammation of bile duct, we try following procedures for elimination of gallstone: 1) endoscopic mechanical lithotripter (EML) 2) (Extracorporeal shock wave lithotripsy (ESWL) And we have got the excellent results. PMID- 8366608 TI - [Biliary tract infection]. AB - Biliary tract infection is a frequently encountered clinical problem and requires prompt diagnosis, proper understanding of the pathologic manifestations, and adequate treatment. If not managed properly, it can be the cause of disseminated intravascular coagulation and multiple organ failure and its prognosis can be fatal. This paper focuses on two of its representative diseases: acute cholecystitis and acute cholangitis. PMID- 8366610 TI - [Acute biliary pancreatitis]. AB - Pathogenesis, diagnosis, predicting severity, and treatment of acute biliary pancreatitis are reviewed. Clinical characteristics, treatment and outcome were investigated in 23 patients with severe, acute biliary pancreatitis. Conservative treatment is successful in most of patients with acute biliary pancreatitis. Surgical treatment for biliary stones should be followed by an initial conservative treatment. However, in patients with severe pancreatitis, who has poor prognosis, intensive care is necessary and surgical treatment must be adequately performed, in failure of active medical treatments. In these cases, the timing of operation is important. When biliary lesions, acute septic cholangitis or impacted ampullary stones, are responsible for the severe condition, and can't be treated by a medical procedure, such as PTCD or EST, surgical treatment of the biliary tract should be considered. PMID- 8366611 TI - [Gallstone disease in pregnancy]. AB - The incidence of gallstone disease in Japan has increased in recent several decades, and this is associated with the increased fat intake, especially for cholesterol stones. Women are more likely to develop gallstones than men. This sex-related difference in incidence is thought to be related with pregnancy. There are several reports that suggest the lithogenicity of estrogen which increases the content of cholesterol in bile. And there are another reports that gallbladder emptying becomes poor during pregnancy because of the effect of progesterone. The management of gallstone disease in pregnancy is different at the stages of pregnancy, severity of attack, and the presence of infection. The gallstone attack should be treated supportively during pregnancy, especially at the early stage and late stage. And after delivery, cholecystectomy should be performed. As for recurrent attacks, severe attacks or attacks associated with infection, cholecystectomy should be considered even during pregnancy. In the middle stage of pregnancy, cholecystectomy can be performed safely. In the case in which cholecystectomy should be avoided, percutaneous transhepatic biliary drainage can be performed. The common bile duct stone, cholangitis and biliary pancreatitis should be diagnosed be ERCP, and after definitive diagnosis, treatment with endoscopic sphincterotomy should be tried. PMID- 8366612 TI - [Post-gastrectomy gallstone disease]. AB - Biliary tree of gastrectomized patients was examined with ultrasonography to investigate the factors affecting post-gastrectomy gallstone formation. Only gallbladder stone was found in 57 (18.9%). In 11 (20.0%) of 55 patients, stones had developed within 2 years after surgery, but no difference in incidence were observed by sex and age. Sixty four gastrectomized gallstone patients were examined in respect to the kind of gallstone. Patients with cholesterol gallstones were 18 (28.1%), patients with black gallstones were 29 (45.3%) and patients with calcium bilirubinate gallstones were 17 (26.6%). The incidence rate of cholesterol gallstones was lower and the rate of black gallstones and calcium bilirubinate gallstones was higher than that of non-gastrectomized patients. In conclusion, the incidence of pigment gallstones is very high in gastrectomized patients. PMID- 8366613 TI - [Treatment strategy of gallstone patients under special conditions gallstone in the elderly]. AB - We have treated 894 gallstone patients for these five years. The average age was 55.47 and 163 cases (18.2%) were more than 70 year-old. One of the important characteristics of the aged gallstone patients that they often had bile duct stones causing acute obstructive cholangitis. The other was that they accompanied another organ disorders. Early biliary drainage was the best way to avoid multiple organ failure under such conditions. Principally, surgical treatment if it's possible, was most reliable for bile duct stones. Thirty-five patients of bile duct stones were treated with our new surgical procedure. That was primary closure technique of the common bile duct following lithotomy under pre- or intra operative insertion of naso-biliary drainage catheter. Especially in the elderly, this technique was useful to reduce post operative hospital stay by 19 days compared with the ordinary T-tube drainage. PMID- 8366614 TI - [Telomere, cellular senescence and transformation]. AB - Telomere is the structure which is located on both ends of individual chromosomes in eukaryotes. The DNA sequence of the telomere consists of Guanine-rich tandem repeat, i.e., (TTAGGG)n in man. Telomere protects the end of the chromosome from fusion or deletion and maintains the stability of the chromosome and is synthesized by telomerase, a ribonucleoprotein. Telomere reduction is observed with cell senescence and immortalization, both in vivo and in vitro. Thus, telomere is considered to be a "clock" which measures the life span of cells, and its length is altered by cellular senescence and immortalization. PMID- 8366615 TI - [Antiviral compounds: current approaches for development]. AB - Recent dynamic advances of molecular biology have been discovering the specific virus functions and replication strategies that differ greatly from their host cells. These studies made it possible to design the antiviral agents which block virus replication specifically. In this paper, we review the recent approach for development of anti-HIV agents and the problems of anti-herpes compounds applied in clinical treatment. PMID- 8366616 TI - [Recent trends of gene therapy of human patients]. AB - Recent trends of gene therapy in the USA, European countries and in Japan are reviewed. Although only the gene treatment for ADA deficiency was shown to be effective, many clinical trials of gene treatment for cancer or other disorders have already been approved by the RAC of NIH. In Japan, the Ministry of Health and Welfare started to make a guide line for human somatic cell gene treatment. This guide line is expected to be publicized by the end of March of 1993. It is therefore, expected that gene treatment will start in Japan in the very near future. PMID- 8366618 TI - [Pulmonary aspergillosis with air-fluid level in a cavity]. AB - We experienced 17 cases of pulmonary aspergillosis with air-fluid level in a cavity. The incidence of this phenomenon was 39% in 44 patients who were diagnosed as having pulmonary aspergillosis during the period from 1983 to 1991 at Yaizu Municipal Hospital. There were two clinical patterns: primary air-fluid type and secondary air-fluid type. Primary air-fluid type disease began with cavitation with an air-fluid level. Our 14 cases of this type had severe symptoms and inflammatory reaction. In secondary air-fluid type, the fungus ball disappeared and an air-fluid level appeared in a cavity during treatment. Our 3 cases of this type had only mild cough and sputum. The fluid disappeared later in two of these three cases. Some cases of primary air-fluid type changed to fungus ball type or productive aspergilloma on the inner wall of a cavity. Primary air fluid type thus seems to represent incipient pulmonary aspergilloma, and to be important for early diagnosis and treatment. Of the immunological tests, precipitins to Aspergillus fumigatus proved most useful for early diagnosis. PMID- 8366617 TI - [Mechanism of constriction and dilatation of pulmonary artery induced by hydrogen peroxide]. AB - Hydrogen peroxide (H2O2) is known to cause transient pulmonary vasoconstriction in isolated lungs perfused with a solution containing no blood components, by inducing vasoactive arachidonate metabolites such as thromboxane A2 (TXA2). However, the exact site of production of the vasoactive arachidonates in the lung tissue is unclear. Using isolated main pulmonary arterial rings obtained from male Sprague-Dawley rats (B.W. 300-350 g), we attempted to examine the arachidonate metabolism, especially that mediated by cyclooxygenase, in the vascular wall of pulmonary artery without endothelium. Changes in isometric tension were used to measure contraction or dilatation of the ring preparation. H2O2 caused transient contraction of the ring, which was treated previously with a solution containing a high concentration of potassium (20 mM). The contractile response was enhanced in parallel with the concentration of H2O2 in the presence or absence of endothelium. Catalase (1000 U/ml), a H2O2 scavenger, completely inhibited the response of the isolated ring (without endothelium) to H2O2. OKY 046 (10(-5) and 10(-4) M), a TXA2 synthetase blocker, partially attenuated the contractile response induced by H2O2. ONO-3708 (10(-5) M), a TXA2 and prostaglandin H2 receptor blocker, fully inhibited the vasoconstriction and caused relaxation of the ring without endothelium after addition of H2O2. Indomethacin (5 microM), a cyclooxygenase inactivator, completely inhibited both vasoconstriction and vasodilation of the denuded ring. H2O2 also induced the release of 6-keto-prostaglandin F1 alpha, a stable metabolite of the vasodilator, prostacyclin, from the pulmonary artery without endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366619 TI - [A clinical study of respiratory infection with methicillin-resistant Staphylococcus aureus (MRSA)]. AB - We investigated patients with positive sputum for MRSA at Daido Hospital. The study was conducted from 1990 to 1991. The number of cases with positive sputum for MRSA is moderately increased. We classified 116 MRSA isolated cases into three groups, 67 cases of colonization with MRSA, 26 cases of suspected bronchopulmonary infection, and 23 cases of bronchopulmonary infection with MRSA. The coagulase types of MRSA were type II or type II + III. Examination of the susceptibility to antibiotics of MRSA showed that all MRSA strains were susceptible to sulfamethoxazole trimethoprim, arbekacin, and vancomycin. A few strains were resistant to rifampicin. There were no differences in coagulase types and susceptibility to antibiotics between the three groups. Bronchopulmonary infection with MRSA was frequently associated with underlying bronchopulmonary disease, whether malignant or not. Risk factors for MRSA bronchopulmonary infection could not be identified, but the prognosis of MRSA bronchopulmonary infection was poor in cases with higher grade of performance status. MRSA eradication rate in sputum after therapy was low, and was not improved by adding inhalation of antibiotics including vancomycin to systemic chemotherapy. This investigation demonstrates the importance of environmental prevention of MRSA infection in hospitals. PMID- 8366620 TI - [Changes in plasma electrolytes during exercise in normal subjects--with special reference to the concentration of potassium and inorganic phosphate (Pi)]. AB - In 8 healthy adults, changes in plasma electrolyte levels (Na+, Cl-, Ca2+, Pi and lactate) and respiratory parameters (VE, VO2 and VCO2) were examined during incremental exercise on a treadmill. Na+, Cl- and Ca2+ increased significantly near the end of maximal exercise and the early phase of the recovery period. Considering the 14% decrease in plasma volume, the increases in Na+, Cl-, and Ca2+ were not significant, while the increases in K+, Pi and lactate were significant. During incremental exercise, the concentration of K+ significantly correlated with minute ventilation (r = 0.994, p < 0.0001). Two minutes after the completion of exercise, K+ decreased below the pre-exercise level. The inflection point of VE on VO2 appeared earlier than that of K+ on VO2. The results suggest that some other factor which may contribute to the control of ventilation during exercise should be considered in addition to K+. Lactate and Pi began to increase 5 and 8 minutes, respectively, after the start of exercise. Even after the completion of exercise, these two parameters remained significantly higher than the pre-exercise level. During incremental exercise, the concentration of Pi increased concomitantly with time, and significantly correlated with VE. On the other hand, in the early stage of exercise, the concentration of lactate remained at the pre-exercise level. These results suggest that the increase in plasma Pi is responsible for the state of metabolism in the muscle in addition to lactic acidosis. PMID- 8366621 TI - [Relationship between limitation of daily life and prognosis in patients with sequelae of tuberculosis treated with long-term oxygen therapy]. AB - The sequelae of tuberculosis (TBC) sometimes causes severe restrictive lung disorders. In Japan, lung tuberculosis was pandemic up to the 1950s, with TBC being a major underlying disease of chronic respiratory failure and cor pulmonale. Until the end of 1991, we encountered 95 cases of Home Oxygen Therapy (HOT) in Ogaki area, 30 of which were patients with TBC. To clarify factors affecting the prognosis of these patients, we examined background factors, directing special attention to daily activities. In this study, 10 inactive patients (Group A) whose daily activity was limited to indoors and 10 control patients (Group B) whose age, vital capacity and arterial PO2 were equal to inactive patients, from the 30 TBC cases were used. A comparison was made of the prognoses. Among the patients, activity was closely related to dyspnea grade and arterial PCO2. Group A patients showed more marked dyspnea and lower arterial PCO2 than those of group B patients. Percentage home stay and cumulative survival rates of Group A patients (percentage home stay, 59.2 +/- 38.7% and 3 year survival, 26.3%) were significantly less than those of Group B patients (91.0 +/- 16.4% and 87.5%, p < 0.05, respectively). Among chronic pulmonary emphysema patients treated with HOT, no significant relation between activity and prognosis could be found, when factors of age, arterial PO2 and forced expiratory volume in 1 sec were excluded. There would thus appear to be a close relation between activity and prognosis in TBC patients specific for underlying disease. PMID- 8366622 TI - [Pulmonary circulatory disturbance following endoscopic injection sclerotherapy]. AB - We compared arterial blood gas analysis and 99mTc-MAA lung perfusion scintigraphy before and after endoscopic injection sclerotherapy (EIS) in 17 cases of esophageal varices complicating liver cirrhosis. EIS was performed by the intra variceal injection method with 5% ethanolamine oleate (EO) as the sclerosant agent. In blood gas analysis, the mean values of partial arterial oxygen tension (PaO2) and oxygen saturation (SaO2) were decreased, and the mean value of alveolar-arterial O2 difference (AaDO2) was increased, compared with before EIS while breathing room air. On lung perfusion scintigram, the pulmonary blood flow was markedly decreased, demonstrating hypoperfusion and/or perfusion defect, compared with before EIS in most the cases. It was suggested that pulmonary embolism and/or pulmonary circulatory disturbance occurred after EIS. It is important to note that pulmonary circulatory disturbances potentially may occur after EIS without any accompanying symptoms such as dyspnea, cough, or hemoptysis. PMID- 8366623 TI - [Hydraulic conductivity of visceral pleura in dogs]. AB - We measured the hydraulic conductivity of the visceral pleura in seven mongrel dogs in situ. The left chest was opened at the seventh intercostal space. A hemispherical capsule, filled with physiological saline, was attached to the visceral pleura of the left lower lobe by the negative pressure in the plate, using a vacuum pump. Transpleural fluid flow (V) was measured at different intracapsular pressures (delta P). The hydraulic conductivity was calculated from the relation between fluid flow and intracapsular pressure, i.e., the slope of the linear regression line. The hydraulic conductivity was 1.49 +/- 0.68 (mean +/ SD) nL.min-1 x cmH2O-2. Our values were smaller than those of former reports obtained in vivo. It is suggested that the dynamics mechanisms of plural effusion may be clarified by studies using our method. PMID- 8366624 TI - [Effect of surfactant on mouse alveolar macrophage cytotoxicity]. AB - Surfactant has been shown to have several immunologic activities in addition to its property of lowering tension. To investigate the effect of surfactant on alveolar macrophage cytotoxicity against tumor cells, we compared the cytolytic activity, tumor necrosis factor (TNF) activity and L-arginine-dependent NO2- production of mouse alveolar macrophages in the presence of surfactant with those of alveolar macrophages alone. Furthermore, we measured the concentrations of inositol-1,4,5, triphosphate (IP3) and diacylglycerol (DG) both of which are second messengers of intracellular signals. Cytolysis, TNF activity and NO2- production were enhanced by lipopolysaccharide (LPS) and interferon-gamma (IFN gamma). This enhancement was further increased by addition of surfactant. The surfactant did not enhance the concentration of IP3, but enhanced that of DG in alveolar macrophages activated by LPS or IFN-gamma. These data suggest that surfactant upregulated the enhancement of alveolar macrophage cytotoxicity by LPS and IFN-gamma, and this effect was related to an increase in the concentration of DG in activated alveolar macrophages. PMID- 8366625 TI - [A case of pulmonary malignant lymphoma with macroglobulinemia and cecal cancer]. AB - A 69-year-old female was found to have an abnormal shadow in the right middle lobe during examination for operation for cecal cancer. Ten months later, she was admitted to our hospital because of enlargement of the shadow and development of macroglobulinemia. Transbronchial lung biopsy and elevated IgM in BALF (IgM/Alb was 2.75 times that in serum evidently suggested pulmonary malignant lymphoma. CHOP therapy was not effective, and resection of the mass was attempted but was not feasible because of extension of the lesion into the upper and lower lobes. The biopsy specimen obtained during surgery disclosed malignant lymphoma, diffuse small cell type (IgM kappa type, B-cell). Radiation therapy was effective with complete resolution of the shadow. In this case, transbronchial lung biopsy and BAL were useful in the preoperative diagnosis of pulmonary malignant lymphoma. PMID- 8366626 TI - [A case of extraskeletal Ewing's sarcoma of the chest wall]. AB - A 22-year-old woman was admitted to our hospital complaining of high fever, dyspnea and wheeze. Chest X-ray film and CT scan showed a huge mass lesion in the right chest. Histological findings of specimens obtained by both needle biopsy and surgery showed necrotic tissue. She died of rapidly progressive pulmonary metastasis three months after surgery, and at autopsy, the tumor was diagnosed as extraskeletal Ewing's sarcoma originating from the chest wall. PMID- 8366627 TI - [A case of pleural involvement followed by idiopathic retroperitoneal fibrosis]. AB - We report a rare case of pleural involvement followed by idiopathic retroperitoneal fibrosis in a 55-year-old man. He complained of right chest pain and his chest radiogram showed pleural thickening and calcification. Chest X-ray computed tomogram (CT) also showed a mass-like pleural thickening and a soft tissue density lesion surrounding the thoracic aorta, suggesting fibrosis. By open pleural biopsy, the mass-like pleural lesion was diagnosed as chronic pleuritis. Three years later, the patient experienced difficulty in urination, and bilateral hydronephrosis which was probably due to a retroperitoneal lesion was detected. Abdominal X-ray CT revealed a retroperitoneal lesion of soft tissue density comprised of a smooth and clearly delineated mass which encased the large vessels and ureters, compatible with retroperitoneal fibrosis. Although it was not possible to biopsy the retroperitoneal lesion, the lesion was clinically and radiologically thought to be retroperitoneal fibrosis. We could not determine the etiology of these findings, but such a case of pleural involvement followed by idiopathic retroperitoneal fibrosis was considered to be very rare. PMID- 8366628 TI - [A case of alveolar microlithiasis which developed spontaneous pneumothorax due to progression of emphysematous bullae during 34 years after established diagnosis]. AB - The patient was a 46-year-old man who was taxi driver. He had received therapy for miliary tuberculosis from nine years old, and the diagnosis of alveolar microlithiasis was made by open lung biopsy at twelve years of age in 1956. At that time, there were no emphysematous bullae, and slight alveolar wall thickening was observed histopathologically. After a 34 year interval, he developed spontaneous pneumothorax with sudden dyspnea. Multiple emphysematous bullae were found at thoracoscopy performed to treat the pneumothorax. Arterial blood gas analysis after resolution of the pneumothorax showed hypoxia with a PO2 of 65.4 torr, and lung function tests revealed restrictive disorder. Thus, in this patient, emphysematous bullae progressed resulting in a pneumothorax, and lung fibrosis also developed 34 years after the diagnosis of alveolar microlithiasis. Alveolar microlithiasis is occasionally misdiagnosed as miliary tuberculosis. The authors stress that the chest roentgenographic finding of ari bronchogram demonstrating intra-alveolar foci is an important sign in the differential diagnosis. PMID- 8366629 TI - [Aniline-induced methemoglobinemia monitored by pulse oximetry]. AB - A case of aniline-induced methemoglobinemia is reported. When the pulse oximeter reading (SpO2) was 80%, the oxygen saturation measured by a co-oximeter (SaO2) was 61.2%, the oxygen saturation calculated from PaO2 values was 98.9% and methemoglobin level was 38.8%. After methylene blue injection, methemoglobin level decreased gradually. With a decrease of methemoglobin level, SpO2 approached SaO2. If disparity between SpO2 and the oxygen saturation calculated from PaO2 values is noted, the presence of methemoglobinemia must be suspected. In clinical situations, the pulse oximeter permits the continuous noninvasive monitoring of oxygen saturation. It is necessary, however, to consider the potential errors in pulse oximetry. PMID- 8366630 TI - [A case of so-called benign metastasizing leiomyoma responsive to progesterone]. AB - A 47-year-old female, who had undergone hysterectomy and unilateral oophorectomy in 1975, was admitted to our hospital in 1989 because chest X-ray films revealed an increase in size and number of pulmonary nodules for two years. On admission, a left inguinal tumor was found and histologically it consisted of smooth muscle cells with nuclear atypia arranged in interlacing fascicles. An open-lung biopsy was performed. Pulmonary tumors revealed similar histology to the inguinal tumor. They were diagnosed as metastatic low-grade leiomyosarcoma, so-called benign metastasizing leiomyoma (BML), on the basis of location and history, reinforced by mild histologic atypia. The tumor contained a high progesterone receptor level (400 fmol/mg). Therefore, medroxyprogesterone acetate, 600 mg daily, was administered orally. At two years the pulmonary lesions had regressed. BML is a rare condition, considered to be pulmonary metastasis from low-grade leiomyosarcoma of the uterus. Measuring estrogen and progesterone receptors in lung biopy material may help determine the most appropriate therapy. PMID- 8366631 TI - [A case of congenital absence of the right pulmonary artery]. AB - A 14-year-old girl was admitted to ur hospital with pneumonia of the left lung, and some residual abnormalities were noted on chest X-ray film after recovering, which showed a small right hemithorax, displacement of the heart and mediastinal structures toward the right, and a small right hilum. There was no radioisotope accumulation in the right lung on pulmonary perfusion scintigraphy, and pulmonary angiography showed proximal interruption of the right pulmonary artery. Contrast enhanced computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the absence of the right main pulmonary artery and enabled congenital absence to be distinguished from acquired obstruction of the artery. The peripheral pulmonary arteries in the affected lung were identified on CT, and radioisotope angiography showed a blood supply to it from the systemic circulation. However, aortography and bronchial arteriography failed to show an aberrant systemic pulmonary artery. 133Xenon ventilation-perfusion scintigraphy showed that the ventilation of the affected lung was about 50% of that of the left lung, but there appeared to be no gas exchange by the affected lung. Her prognosis was expected to be good, because she had neither cardiovascular abnormalities nor had developed pulmonary hypertension. PMID- 8366632 TI - [A case of drug induced pneumonitis caused by oral etoposide]. AB - We report a case of drug induced pneumonitis caused by oral etoposide. A 63-year old man was admitted to our hospital in August 1991 because of low grade fever and dyspnea. He underwent right upper lobectomy on Nov. 27th, 1990 for lung cancer (squamous cell carcinoma), and courses of adjuvant chemotherapy (CBDCA, IFX, etoposide) during the following admission period. He was discharged on Feb. 14th, 1991, and as an outpatient, oral etoposide (25 mg/day) was administered for about 7 months (6,125 mg in total). Chest X-ray film on admission showed reticulonodular shadows in bilateral lung fields, and computed tomography showed diffuse interstitial shadows. Blood gas analysis showed marked hypoxemia (PaO2 breathing room air was 48.4 Torr). Transbronchial lung biopsy revealed edema of the alveolar walls and marked proliferation of type II alveolar epithelial cells, suggesting cytotoxic reaction. After termination of etoposide administration and following steroid pulse therapy, both clinical symptoms and hypoxemia were ameliorated. To our knowledge, this is the first report of etoposide-induced pneumonitis. PMID- 8366634 TI - Responsibility. PMID- 8366635 TI - Investigating drug diversion on a hospital unit: a team approach. PMID- 8366636 TI - What if peer assistance weren't? PMID- 8366633 TI - [A case of allergic bronchopulmonary candidiasis improved with steroid inhalation]. AB - A 49-year-old woman was admitted to hospital because of productive cough and dyspnea. She had been well two months before admission, when she developed an attack of asthma. Chest roentgenogram taken on admission revealed numerous shadows of inhomogeneous density in both lungs. Laboratory findings showed leukocytosis with eosinophilia (25%), high IgE level in serum and positive RAST score to Candida albicans. A diagnosis of allergic bronchopulmonary candidiasis was made by these laboratory data and clinical course. The patient was treated successfully by oral administration of methylprednisolone and inhalation of amphotericin B, but she had a relapse of the disease on cessation of steroid medication. Inhalation of beclomethasone dipropionate and procaterol hydrochloride was commenced. Thereafter, pulmonary infiltration and clinical symptoms improved after three weeks. PMID- 8366637 TI - The twelve steps: a basic understanding. PMID- 8366638 TI - Help for the helper. PMID- 8366639 TI - [Treatment of cardiogenic shock in myocardial infarction with intraaortic counterpulsation]. AB - The purpose of this study was to analyse the effects of intraaortic balloon counterpulsation (IABP) in treatment of patients with acute myocardial infarction (MI) complicated by cardiogenic shock. The study group consists of 20 consecutive patients (13 males and 7 females, aged 38-82 years) with cardiogenic shock developed in the course of MI. Catecholamines were administrated in all patients before intraaortic balloon pumping was instituted. IABP was performed using Datascope device. Efficacy of the procedure was determined with invasive measurements of arterial blood pressure and the level of diuresis. Of 20 patients with cardiogenic shock, 7 were successfully treated with IABP and they were discharged from the hospital. PMID- 8366640 TI - [Spontaneous echo contrast in transesophageal echocardiographic examination: clinical ultrasonic analysis]. AB - The clinical and echocardiographic variables related to spontaneous echo contrast were evaluated in a consecutive series of 600 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. The spontaneous contrast was observed in 110 patients (18%). It was seen mainly in the atria; in the left atrium in 98, in the right atrium in 2 patients, in both atria 7, in the vena cava superior and right atrium in 1, in the left atrium and ventricle in 1, and in the false lumen of dissected aorta. Spontaneous atrial contrast was never seen in the absence of cardiac abnormality. There was a high incidence of atrial spontaneous echo contrast in cases of significant mitral stenosis, mitral valve prosthesis, atrial fibrillation, enlarged left atrium and absence of significant mitral regurgitation which were showed by univariate analysis. Multivariate analysis showed that atrial fibrillation, significant mitral stenosis and enlarged left atrium were independent factors for the presence of spontaneous contrast. Thus, spontaneous echocardiographic contrast detected by transesophageal echocardiography is a common finding in patients with mitral stenosis, atrial fibrillation and enlarged left atrium, in the absence of significant mitral regurgitation. PMID- 8366641 TI - [Hemodynamic effects of one administration of l-dopa in patients with left ventricular heart failure (introductory remarks)]. AB - The study group consisted of 8 men with congestive heart failure. They ranged in age from 33 do 63 years (mean 48). Three patients were in class III NYHA, five in class IV. Idiopathic cardiomyopathy was diagnosed in 6 patients, one individual displayed ischemic heart disease and one patient was after mitral and aortic valve replacement despite a normally functioning prosthetic valve. L-dopa was given orally beginning with 250 mg every six hours until a total daily dose of 4.0 g was achieved with no side effects (patients additionally received 50 mg of pyridoxine hydrochloride). Afterwards L-dopa was withheld for 24-36 hours. Having completed this washout period, patients underwent right heart catheterization, with placement of a balloon-tipped thermodilution catheter in a pulmonary artery, so that balloon inflation allowed recording of the pulmonary capillary wedge pressure. Right atrial and pulmonary arterial pressures were monitored continuously. Systemic arterial pressure was measured by mercury manometer. Cardiac output was determined by the thermodilution technique. Rest and effort hemodynamic measurements were repeated before and one, three hours after administration of 1-dopa. The base-line hemodynamic values were consistent with the clinical presentation of severe congestive heart failure. The average cardiac index (CI-1/min/m2--rest--1.93; 25 Watt-3.1) and stroke volume index (SVI-m1/m2- rest--22.2; 25 Watt-32.0) were markedly lowered. Left ventricular filling pressure and pulmonary artery pressure were elevated. The systemic vascular resistance was significantly increased (SVR -j.W.--rest--22.7; 25 Watt-14.2). Administration of 1-dopa resulted in the increase in cardiac index and stroke volume index accompanied by a substantial reduction in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366642 TI - [Sodium dichloroacetate decreases the size of experimental myocardial infarction in dogs]. AB - The effect of sodium dichloroacetate on the size of myocardial infarction and on the changes of blood lactate and pyruvate levels after coronary artery occlusion were studies in 5 dogs. Sodium dichloroacetate administrated during coronary artery occlusion in dogs limited the size of myocardial necrotic area, simultaneous decrease of lactate and pyruvate levels in peripheral blood was observed. An analysis of lactate levels in blood samples from the coronary sinus and left atrium during coronary artery occlusion and the administration of sodium dichloroacetate suggests that the utilization of lactate by left ventricular myocardium under these conditions is increased. PMID- 8366643 TI - [A new multipolar transesophageal electrode for assessment of activation sequence in the left atrium]. AB - A new multipolar transoesophageal electrode is described. Two patients were analysed. One with recurrent coronary sinus rhythm and the other with concealed WPW syndrome. Obtained recordings showed difference of sequence of left atrial depolarisation during recovery of the sinus rhythm after its overdrive suppression and during provoked tachycardia. Results are very promising and require further investigation. PMID- 8366644 TI - [Myocardial infarction in pregnancy]. AB - We report two cases of pregnant women who developed an acute myocardial infarction. The proposed cause of massive myocardial anterior and interventricular wall infarction of the first patient appears to be bacterial intracoronary thrombus during the course of bacterial endocarditis. Acute insufficiency of the mitral valve caused by rupture chordae tendineae of the anterior mitral left was another complication. Labor contractions occurred on the 13th day of treatment. On the next day the patient gave birth to a healthy child by elective cesarean section. She was also qualified for an operation because of increased signs of left ventricular heart failure. Preoperative coronary angiography revealed occlusion of the anterior descending branch and reconstruction of its periphery. Other vessels were not changed. The patient was subjected to implantation of artificial valve, an aortocoronary by-pass and repair of atrial septal defect. Eighteen months follow up was uneventful. The second case was a 29 year-old pregnant woman who had previously undergone mitral commissurotomy admitted because of an acute myocardial infarction in the II trimester. No complication of the disease was observed. PMID- 8366645 TI - [Intra-aortic balloon counterpulsation. Principle of action. For whom and when? (surgeon's point of view)]. PMID- 8366646 TI - [Intra-aortic balloon counterpulsation--a cardiologist's point of view]. PMID- 8366647 TI - [Intra-aortic balloon counterpulsation--point of view of the cardio-surgeon]. PMID- 8366648 TI - [Intra-aortic balloon counterpulsation--cardio-surgeon's point of view]. PMID- 8366649 TI - [Intra-aortic counterpulsation--cardiologist's point of view]. PMID- 8366650 TI - [The adult with congenital heart defects]. PMID- 8366651 TI - [Exercise echocardiography in diagnosis of ischemic heart disease]. PMID- 8366652 TI - [Augmented activity of the adrenal medulla in young men with positive family history of essential hypertension]. AB - Serum adrenaline (AD) and noradrenaline (NA) were measured by RIA method in two groups of young males: group S (n = 54) with positive family history of essential hypertension (EH) and group K (n = 9) with negative family history of EH (mean age: 24.6 +/- 3.3 i 23.6 +/- 3.6 years respectively). AD and NA concentrations were estimated in basic conditions (AD1, NA1) and after 10 min of passive vertical posture(AD2, NA2). In group S AD1 concentration was higher than in group K (54.4 +/- 24.4 i 37.8 +/- 15.6 pg/ml respectively, p < 0.05). In group S a positive correlation was found between mean systolic blood pressure (SBP) and mean heart rate (HR) estimated during 5-hours monitoring by Spacelab IGR 5300 ambulatory blood pressure and heart rate monitoring system (r = 0.5, p < or = 0.01). Pearson's correlation coefficient (Pcc). In this same group positive correlations were also found between AD2 and SBP - r = 0.31, p < 0.05 (Pcc) and between AD2 and HR: r = 0.33, p < 0.05 (Pcc). Results of 5-hours blood pressure monitoring showed that 15 of 54 males from group S had SBP > 139 mmHg (group S1). In group S1, AD1 and AD2 concentrations were higher than in group K (AD1: 366 +/- 144; 206 +/- 85, p < 0.01 and AD2: 626 +/- 266; 369 +/- 156 fmol/ml, p < 0.05 respectively). No differences were found in AD1, AD2, NA1 and NA2 concentration between group K and normotensive (SBB < 140 mmHg) males with positive family history of EH: group S2. In young males with positive family history of EH, the elevation of blood pressure might be caused by an augmented activity of the adrenal medulla. PMID- 8366653 TI - [Congestive heart failure and ventricular arrhythmia in relation to magnesium, potassium and sodium in serum and erythrocytes]. AB - The aim of this study was to determine magnesium, potassium and sodium in plasma and erythrocytes in patients (14 male, 12 female; the average age 60.3) with congestive heart failure (CHF) (NYHA class II/III, III, IV) who were treated with digitalis, diuretics and vasodilators. All patients were subjected to 24 h ECG monitoring and ventricular arrhythmias classified according to LOWN, were analyzed in relation to electrolyte contents in erythrocytes and serum. Control group consisted of 20 persons (17 male; 3 female: the average age 58.7 years). Plasma and erythrocyte K and Na were determined by flame spectrophotometer; Mg was assayed by atomic absorption spectrophotometer. Statistical analysis was made by t-Student test. Results obtained suggest that patients with CHF require supplementation K+ with Mg2+ (tab. I). Our study has not revealed expected interrelationships between ventricular arrhythmias and electrolyte disturbances in patients with CHF. It should be stressed, however, that the small numbers of patients in the subgroups in our study might have blurred the possible relationship. PMID- 8366654 TI - [Complications associated with use of atrial electrodes]. AB - The higher complication rate with atrial than ventricular leads make the physiological mode of pacing less popular. The aim of this study was to assess the complications associated with atrial leads. Between July 1985 and December 1991 we inserted 174 atrial leads in 165 patients (pts) with sick sinus syndrome or/and a-v block (AAI and DDD system respectively). A variety of different types of unipolar leads have been used: passive fixation simple or J shaped with the porous tip of vitreus-carbon (n = 49) and platinum-iridium (n = 78) or polished tip of Elgiloy (n = 18), active fixation (n = 29). The leads were manufactured by Siemens-Elema, CPI, Biotronik, Medtronic and Vitatron. All leads have similar acute electrical characteristics. The mean follow-up period lasted 28 months (12 83) until June 1992. We observed the following complications: displacement of electrode tip in 16 pts (9.7%), the disturbances of sensing in 10 pts (6%), 3rd degree of a-v block in 6 pts (5.4%) of 111 pts with AAI pacing, the exit-block in 3 pts (1.8%), suppuration in 3 pts (1.8%) in pacemaker area, various in 1 pt (0.6%). Total complication rate, which required reoperation was 20.6%. Complications associated with atrial leads implantation are not dangerous, may be easily treated and should not limit the indication for physiological pacing. PMID- 8366655 TI - [Change of right ventricle performance caused by intravenous nitroglycerin infusion in patients with isolated mitral stenosis]. AB - The impact of intravenous infusion of nitroglycerin (NTG) on the conditions of the right ventricle (RV) load was assessed in a group of 27 patients with isolated mitral stenosis (SM). Swan-Ganz catheter was used to assess the parameters influencing preload and afterload of the RV at rest and during effort of its performance under NTG. NTG infusion caused lowering of RV filling pressure at rest (from 5.1 +/- 2.8 to 3.2 +/- 1.9 mm Hg, p < 0.001), and during effort (from 7.6 +/- 3.6 to 4.9 +/- 2.2 mg Hg, p < 0.001), lowering of mean pulmonary artery pressure at rest (from 27 +/- 10.7 to 19.8 +/- 9.2 mm Hg, p < 0.001) and during effort (from 48.6 +/- 15.5 to 39.4 +/- 16.1 mm Hg, p < 0.001), and lowering of capillary wedge pressure at rest (from 17.1 +/- 6.9 to 12.7 +/- 6.2 mm Hg, p < 0.001) and during effort (from 32.9 +/- 10.1 to 25.9 +/- 8.4 mm Hg, p < 0.001). NTG infusion lowers pulmonary vascular resistance at rest (from 2.5 +/- 1.6 to 1.9 +/- 1.5 W.u., p < 0.001) and during effort (from 2.9 +/- 2.0 to 2.4 +/ 1.9 W.u., p < 0.001). NTG causes beneficial lowering of the stroke work index of the RV at rest (from the average of 9.9 +/- 5.3 to the average of 6.4 +/- 3.9 pm/m2, p < 0.001) and during effort (from the average of 19.1 +/- 9.1 to the average of 15.7 +/- 9.0 pm/m2, p < 0.001). Beneficial hemodynamic effect of NTG on preload and afterload of the RV in patients with isolated SM was demonstrated. PMID- 8366656 TI - [Echocardiography of the fetal heart. Analysis of 350 successive examinations]. AB - From July 1st 1990 do June 30th 1992 517 fetal echocardiography examinations were performed at the Department of Sonography, Polish Mother Memorial Hospital, (Toshiba 270 SA or Acuson 128 XP) between 20th and 41st gestation weeks. The medical indications for fetal heart examinations were presented. On the basis of echo preliminary diagnoses with 350 newborn's clinical assessment, our own results were reviewed. Correct heart anatomy was described in 94%. In conclusions we suggest that fetal heart assessment (anatomy of the 4 chambers) should be included in a routine screening obstetrical scan in the second half of the pregnancy. PMID- 8366657 TI - [Left ventricular outflow obstruction as a result of external cardiac compression by a mediastinal tumor]. AB - A case of left ventricular outflow tract stenosis resulted from compression of the heart is presented. This symptomatic cardiovascular lesion was produced by extensive growth of mediastinal tumour. Numerous noninvasive methods were necessary to establish this difficult diagnosis. The patient underwent surgery that disclosed a benign process (of neurofibroma). After tumour's resection marked hemodynamic signs subsided. PMID- 8366658 TI - [Selective catheter ablation of the slow pathway in a patient with recurrent atrioventricular nodal reentrant tachycardia]. AB - The case of a 35 year-old patient with recurrent, sustained atrioventricular nodal reentry tachycardia (AVNRT)--type slow/fast--refractory to group IA, IC, II, IV antiarrhythmic agents is presented. The maximum rate of the tachycardia was 280/min. During the antiarrhythmic treatment with group IA, IC and IV agents the tachycardia rate was 230/min. The effective refractory period (ERP) of the slow pathway was 200 ms in antegrade direction. ERP of the fast pathway was 260 ms in antegrade and 210 ms in retrograde direction. Ablation of the slow pathway was performed with radiofrequency energy (device HAT 200 S manufactured by Osypka GMBH, catheter Cereblate No 6). The total ablation time was 96 s, maximal temperature of the effective ablation time was 51 centrigrades. Total energy delivered was 2316 J. The ablation caused neither atrioventricular conduction block nor any damage to the heart structure other than the slow conduction pathway. After the ablation there are no evidence of conduction through the slow pathway. Conduction in anterograde and retrograde direction occurs through the fast pathway. No AVNRT were observed. After ablation the patient has no antiarrhythmic treatment. PMID- 8366659 TI - [Is it possible to predict progress in hypertension]. PMID- 8366660 TI - [Ischemic heart disease should have causal treatment]. PMID- 8366661 TI - High density lipoprotein and low density lipoprotein attenuate the inhibitory effects of oxidized low density lipoprotein on endothelium-dependent arterial relaxation. AB - We have recently reported that oxidized low density lipoprotein (ox-LDL) inhibits endothelium-dependent arterial relaxation through its increased lysophosphatidylcholine (LPC). In this study we examined whether high density lipoprotein (HDL) as well as native low density lipoprotein have any effects on the inhibition of endothelium-dependent relaxation by ox-LDL in isolated strips of rabbit thoracic aorta. Both LDL and HDL were isolated from normal human plasma and LDL was oxidized by exposure to copper. Preincubation of arterial strips with ox-LDL (0.1-0.5 mg protein/ml) inhibited endothelium-dependent relaxation to acetylcholine (ACh) in a concentration-dependent manner. HDL (1 mg protein/ml) by itself had no effect on the relaxation to ACh. In the presence of HDL, the inhibition by ox-LDL was markedly reduced. In addition, native LDL also attenuated the inhibition of endothelium-dependent relaxation by ox-LDL. Thus, HDL and native LDL may have salutary effects against the impairment of endothelium-mediated vasodilation in atherosclerotic arteries. PMID- 8366662 TI - The stellate cells phenotypic transformation in the CCl4- injured liver fibrosis of ICR mice: their desmin immunoreactivity and vitamin A storage. AB - To elucidate the process of phenotypic transformation of stellate cells which were responsible in the production of collagen fibers, ICR mice were injected subcutaneously with CCl4 twice weekly for 5 weeks and the livers were examined by light and electron microscopy every week. Stellate cells were detected by desmin immunoreaction and vitamin A-autofluorescence. In the first week, following cell necrosis in the pericentral areas, granulomas were formed. Two distinct stellate cell phenotypes were developed i.e. desmin-negative cells in the granuloma and a row of intense desmin-positive cells in its boundaries. Both phenotypes seemed to be derived mostly from perisinusoidal stellate cells and involved in collagen synthesis as evidenced by the presence of reticulin meshwork within the granulomas. The meshwork formation was the initial stage of a new septum formation since in the second week the intense desmin-positive cell rows were closer to the central vein concomitant with the growth of several protrusions to form thin layer septa towards neighboring central or portal veins. The myofibroblast-like cells in the septa with features interposed between stellate cells and myofibroblasts were likely derived from the stellate cells phenotypes. During the transformation of stellate cells, the decline of vitamin A storage was accompanied by the formation of connective tissue septa. The desmin immunoreactivity and vitamin A storage in the stellate cell phenotypes during liver fibrogenesis described in this study may reveal their phenotypic transformation in association with the collagen synthesis. PMID- 8366663 TI - The osteogenic potential of fracture hematoma and its mechanism on bone formation -through fracture hematoma culture and transplantation of freeze-dried hematoma. AB - This study was conducted to provide further evidence of the inherent osteogenic potential of the fracture hematoma. The fracture hematoma was separated into its cellular and extracellular elements. The hematoma cells were cultured to study bone formation by the cellular elements alone. Bone formation acceleration factor was added to the cultured fracture hematoma cells. The cell responded to this stimulation by differentiation into chondrocytes. Fracture hematoma was freeze dried to study the presence of osteoinduction by the extracellular factors in the fracture hematoma. The freeze-dried fracture hematoma was packaged in methylmethacrylate pellets and within capsules of hydroxyapatite. These pellets and capsules in response to extracellular humoral factors from the freeze-dried fracture hematoma. The results of experimental implantation of the cultured fracture hematoma cells revealed that these cells had the potential to differentiate into chondroblasts or osteoblasts when bone induction factors and bone acceleration factor was added to their media. These extracellular humoral factors are known to be present in the fracture hematoma. PMID- 8366664 TI - LASA recommendations on education and training for licence holders under the UK Animals (Scientific Procedures) Act 1986--FELASA categories B and C. Report of a committee accepted by LASA Council June 1992. PMID- 8366666 TI - Isolation of Acinetobacter calcoaceticus from the gastrointestinal tracts of SCID mice. AB - Acinetobacter calcoaceticus colonization was observed in the gastrointestinal tracts of C.-B17-scid/scid (SCID) mice, while it was not observed in C.B17-scid/+ and C.B17-+/+ mice with normal immunity housed under the same conditions. A. calcoaceticus and other viable enteric bacteria were not isolated from any organs other than gastrointestinal tract in SCID mice. The mice colonized with this organism were apparently healthy and no significant visceral lesion was observed. PMID- 8366665 TI - Allergy to laboratory mice and rats: a review of its prevention, management, and treatment. AB - Allergy to laboratory animals is reviewed from a management point of view. Personnel issues, medical therapy, legal aspects, animal house environments and work routines are discussed. Modern methods of medical treatment are presented but it is recommended that environmental control should be given priority over drugs. Several ventilation and building design systems are reviewed from an ALA viewpoint. New technology (including down-ventilated benches, ventilated cages) is reviewed and possible effectiveness analysed. These systems, though potentially of value, lack adequate testing under clinical conditions. We conclude that there are many clinically untested techniques that remain to be proven and whose efficacy has not been documented. PMID- 8366667 TI - A spontaneous outbreak of Theiler's encephalomyelitis in a colony of severe combined immunodeficient mice in the UK. AB - Severe Combined Immunodeficient (SCID) mice lack both T and B lymphocytes which makes them highly susceptible to infectious agents. In the present communication, we describe an outbreak of Theiler's encephalomyelitis in a colony of SCID mice which was characterized by an unusually high prevalence of clinically overt cases. Diagnosis was based on the clinical signs, histological lesions and presence of antibodies in contemporaneous immunocompetent mice. This is the first report of this disease in SCID mice and, to our knowledge, also the first reported outbreak of Theiler's encephalomyelitis in the UK. PMID- 8366668 TI - Handling and diet-induced atherosclerosis in rabbits. AB - Atherosclerosis was induced in rabbits by feeding them a 2% cholesterol diet (CHOL) during a 5-week period. Twelve rabbits were fed with increasing amounts of CHOL food until the ad libitum level was reached, whereas in 24 other rabbits the food was limited to the amount eaten by the lowest consumer of the group to reduce individual variability in total amount of food consumed. Twice a day, half of the rabbits were handled carefully, the other half had normal laboratory practice contact with their caretaker. Feed intake and amount of atherosclerosis were determined for all experimental animals, while for the handled animals behavioural parameters and changes were recorded daily and per animal. On average the handled and non-handled rabbits took the same amount of food per week, although there were large individual differences. The handled animals showed some behavioural adaptation to being handled. Handling had no influence on atherosclerosis size; this latter measure was only roughly determined by the amount of CHOL food eaten. PMID- 8366669 TI - Evaluation of the Clinitek 200 urinary test-strip reader in the analysis of dog and rat urines in pre-clinical toxicology studies. AB - The performance of a clinical urinary test-strip reader Clinitek 200 was evaluated for dog and rat urines, in the context of pre-clinical toxicology studies. No major discrepancies were found between data generated by visual estimation or automatic measurement. Analysis of spiked samples showed good agreement between actual concentrations and Clinitek 200 responses for ketone bodies and glucose although a lack of sensitivity was found for the latter. Results for proteins showed over- or underestimation in dog and rat urines respectively at low concentrations, and overestimation at high concentrations in both species. Reproducibility of responses was excellent for ketone bodies, glucose and proteins but was weaker for haemoglobin and bilirubin. High bilirubin concentrations were found to interfere with the haemoglobin reaction. The pH measurements were found to be accurate only around pH 7. Specific gravity measurements were unreliable. Overall, the Clinitek 200 as a screening tool proved sufficiently reliable in the measurement of all parameters tested, with the exception of specific gravity. PMID- 8366670 TI - Development of the KVL segregating inbred strain of the Syrian hamster (Mesocricetus auratus). AB - A new colony of a single segregating inbred strain of the Syrian hamster (Mesocricetus auratus), designated KVL, has recently been developed at the Royal Veterinary and Agricultural University, Copenhagen, Denmark. The segregation occurs with respect to coat colour (pied gray/pied brown) as a result of inbreeding with forced heterozygosity. After 20 generations average litter size was 6.7 at birth and 5.57 at weaning. Mean generation interval was 89.4 days. An initially significant decrease in productivity (inbreeding depression) levelled out with further generations and has now stabilized. The colony is being maintained. PMID- 8366671 TI - A comparison of propofol with other injectable anaesthetics in a rat model for measuring cardiovascular parameters. AB - Prolonged, stable, non-recovery anaesthesia is required for the assessment of the effects of novel compounds on the cardiovascular system. A comparison of injectable anaesthetic agents and combinations (thiobarbital, fentanyl-fluanisone and midazolam, propofol, fentanyl-fluanisone and propofol, and alphaxalone/alphadolone) was made in laboratory rats and the following parameters assessed over 3 h: blood pressure, heart rate and rhythm, respiration rate and depth, analgesia, ease of induction and maintenance of anaesthesia. It was found that propofol, with fentanyl-fluanisone premedication, provided stress-free induction, easily controlled anaesthesia, good analgesia and muscle relaxation for surgery, for up to 3 h duration. Heart rate, blood pressure and respiration remained stable and within normal limits during this time. The other anaesthetics/combinations assessed did not rate as highly in these respects. Propofol, following fentanyl-fluanisone premedication, would appear to be a useful and safe anaesthetic for use in rodents, which avoids significant effects on heart rate or blood pressure. PMID- 8366672 TI - Anaesthetic effects of chloral hydrate, pentobarbitone and urethane in adult male rats. AB - Chloral hydrate, pentobarbitone and urethane were evaluated and compared for onset, duration and depth of anaesthesia, cardiovascular and respiratory effects, nociception and mortality in adult male rats. Chloral hydrate (300 and 400 mg/kg) severely depressed the cardiovascular and respiratory systems. Duration of anaesthesia was linearly related to dose, and anaesthetic depth and analgesia were excellent. Pentobarbital (40 mg/kg) produced a short period of light surgical anaesthesia. Moderate to severe respiratory and cardiovascular depression occurred. Duration of anaesthesia was not related to dose. Urethane (1.2 and 1.5 g/kg) caused moderate cardiovascular depression. In addition, mortality was high at the 1.5 g/kg dose. Duration of anaesthesia was greater than 24 h for most animals. Anaesthesia depth and analgesia were excellent. PMID- 8366673 TI - Whisker trimming behaviour in A2G mice is not prevented by offering means of withdrawal from it. AB - In group-housed laboratory mice whisker trimming (removal of vibrissae) occurs occasionally, but in the A2G strain it is seen almost invariably. We have tested the hypothesis that whisker trimming in A2G mice is not prevented by offering the possibility to withdraw from it. Pairs of male or female mice showing absence of whiskers and/or absence of nasal fur were separated by placing in their cage either one or two wire screens with a 10 mm mesh. Unlike the single screen, the two screens, which were 10 mm apart from each other, excluded nose to mouth contact. After five weeks, whiskers had regrown in mice separated by the double screen, whereas in the pairs separated by the single screen whiskers remained in part absent. This suggests that 2 mice involved in whisker trimming, either actively or passively, co-operate in this behaviour. PMID- 8366674 TI - Unusual patterns of susceptibility to degradation of DNA isolated from tissues in Peromyscus californicus. AB - Isolation of intact, high molecular weight genomic DNA from the livers of 2 subspecies of Peromyscus californicus without excessive degradation was typically unattainable, whereas highly intact DNA from livers of other Peromyscus (field mice) species is invariably obtained using the same isolation methods. Additionally, highly intact DNA was obtained from splenic tissues of adult P. californicus and hepatic tissue of juvenile animals, indicating that the phenomenon is tissue-specific and age-related. PMID- 8366675 TI - Induction of oestrus in cats by photoperiodic manipulations and social stimuli. AB - The development of the nervous system can be studied only if the age of the embryo is exactly known. Since it is difficult to control reproduction in female cats, we tried to time fertilization very precisely to within one hour by using either artificial insemination, or by mating females in oestrus induced by light programming. In one trial, this programming was associated with male or female stimuli according to the work of McClintock (1971, 1978, 1984) and Preti et al. (1986). PMID- 8366676 TI - Induction of alloxan/streptozotocin diabetes in dogs: a revised experimental technique. AB - The diabetic dog represents an excellent model for use in many aspects of diabetic research. The present paper describes, in detail, a reproducible experimental protocol for the successful induction of chemical diabetes in beagles using a combination of the 2 pancreatic beta-cell cytoxic agents alloxan and streptozotocin. PMID- 8366677 TI - A simple gag for the intragastric dosing of guinea pigs (Cavia porcellus). AB - A simple gag has been designed and tested which enables the intragastric intubation of the guinea pig by one person without the use of sedation or light anaesthesia. The system described was used successfully for the daily dosing of materials to 7 guinea-pigs for 14 days without discomfort, aspiration or any injury to the upper gastro-intestinal tract. PMID- 8366679 TI - Determinants of children's health care use: an investigation of psychosocial factors. AB - Factors related to the amount of health care used by 5- to 11-year-old children in a health maintenance organization (HMO) were investigated using a comprehensive multivariate model that assessed the contribution of child health need, mental health, and social functioning; maternal mental health, social support and health care utilization; and family functioning and life events. Mothers reported on the 450 participating children. Health care visits for a two year retrospective period were obtained from the computerized encounter system. Child health need and maternal patterns of health care use were powerful predictors of the overall amount of health care used, and these factors discriminated high users from low users of care. Family conflict was associated with a higher volume of care, while children's depressive symptoms and non-white race were related to lower use. Maternal social support, mental health, and life events were not predictive of use in either full multivariate model. Enabling factors were held relatively constant by participation of all families in a prepaid HMO. The multiple regression model explained 33% of the variance in use, slightly more than in previous studies of children's health care use. When included in a comprehensive analysis, child and family psychosocial characteristics help to explain children's health care use beyond what is possible using simple health and illness variables. The implications of these findings in the development of further research and to the practice of routine pediatric care are discussed. PMID- 8366680 TI - Influencing behavior of physicians ordering laboratory tests: a literature study. AB - There are various reasons why physicians order laboratory tests. Earlier studies have shown that in many cases test-ordering behavior lacks efficiency, resulting in excessive laboratory utilization. Throughout the years various attempts have been made to improve this situation. This review, based on the literature of the past 20 years, gives a survey of interventions and their effectiveness. Various types of education are discussed: general, cost-control oriented and education by means of guidelines, protocols, decision support systems, and feedback (on test ordering or cost). The discussion addresses the quality and apparent restrictions of the studies, and provides possible causes of the widely varying, but mostly low success rates. The long-term effectiveness of interventions aiming at better laboratory ordering is rather unfavorable. PMID- 8366678 TI - Substance use among impoverished medical patients: the effect of housing status and other factors. AB - Four hundred forty-three impoverished medical patients, many of whom were homeless, were studied to determine whether homelessness is an independent predictor of current substance use. Twenty-four percent of the sample of patients were frequent alcohol users (i.e., daily or almost daily), and 18% had recently used illegal drugs (cocaine, heroin, PCP, LSD). Marijuana use was not included in the drug use variable. Bivariate analyses revealed that frequent alcohol was associated with being homeless, male, less educated, a veteran, unemployed, and having more children. Frequent alcohol users also were more likely to be sexually active, have had suicidal thoughts, a previous psychiatric hospitalization or felony conviction, an accident or injury, and poor physical health. Self-reported use of illegal drugs was associated with being younger, U.S. born, never married, having a poor mood, and a mental health problem or substance use by a parent. Use of illegal drugs was associated with being homeless, male, less educated, sexually active, and having a previous felony conviction or psychiatric hospitalization. Once demographic and family characteristics were controlled for, housing status was not related to either frequent alcohol or illegal drug use. Substance use among impoverished patients was a reflection of their historical social backgrounds rather than of their current housing status. Helping these patients to obtain stable housing may not impact the substance use of homeless persons. PMID- 8366681 TI - Influence of the doctor's gender in the satisfaction of the users. AB - This study was carried out in the framework of a wider research project concerning the degree of patient satisfaction with the various types of primary health care. We have studied the relationship among the gender of the doctor, the gender of the patient and the type of primary health care center involved. In 1 type of primary care center (health centers) the medical staff work as a team, whereas in the other (ambulatory care services), the doctor works alone. The survey was conducted among 86 doctors and 860 patients from urban areas in Andalusia, Spain. The degree of patient satisfaction was tested on Likert scales. Both male and female patients attended by female doctors were more satisfied than those attended by male doctors (P < 0.005). Both male and female patients were attended in equal proportions by both male and female doctors (P > 0.20). Overall patient satisfaction values were not affected by the patient's gender (P > 0.40). In comparing overall satisfaction among patients according with the doctor's gender and type of primary health care center, there was a greater degree of satisfaction with female doctors working in health centers (P < 0.01) and no difference existed in ambulatory care services in this area. PMID- 8366682 TI - Comparing hospital perinatal mortality rates: a quality improvement instrument. AB - This article describes the development of a reliable measurement instrument for the quality of perinatal care. The Hospital Perinatal Mortality Comparison (HPMC) predicts the expected perinatal mortality for individual hospitals, based on the perinatal mortality experienced in a group of similar newborns in a large reference population. Out of the 76 hospitals analyzed in 1990, 2 performed significantly better and 5 performed significantly worse than expected according to the logistic regression model. These results may lead to the identification of opportunities for improving the process of medical care in these hospitals. PMID- 8366683 TI - When medical group and HMO part company: disenrollment decisions in Medicare HMOs. AB - Medicare beneficiaries who enroll in "risk contract" Health Maintenance Organizations (HMOs) are covered for services only if they are provided or approved by the HMO. Thus, their enrollment decisions involve selecting a health care delivery system and may be influenced by whether the HMO has contracts with particular providers. Disenrollment decisions, in turn, may be influenced by breaks in contracts between the HMO and its medical groups. This study examines decisions made by Medicare HMO enrollees when their HMO terminated its relationship with a major medical group; the group then signed a contract with a competing HMO. Beneficiaries were forced to choose between remaining with their HMO and switching to another provider, and switching to the competing HMO where they could keep their provider. Beneficiaries demonstrated considerable loyalty to their providers; nearly 60% switched to the competing HMO. Previous research on health care coverage decisions has been based on models which did not address consumers' knowledge, options, and information sources. In this decision context, we found that knowledge and information sources were the most important determinants of beneficiary decisions. PMID- 8366684 TI - Patterns of obstetrical care in single-hospital, rural counties. AB - This study used logistic regression to identify differences in community-level characteristics of small, rural hospitals that provided obstetrical services compared to those that did not. The hypothesis was that community characteristics, such as demographics, geographic location, and socioeconomic status influence the ability of rural hospitals to sustain obstetrical services locally. The sample included small (fewer than 100 beds) non-federal, general, acute-care hospitals that were the only hospitals in their nonmetropolitan counties with fewer than 50,000 people in 1989 (n = 963). Data came from the Area Resource File and the American Hospital Association 1989 Survey. The results suggest that: 1) hospitals in the South are much less likely to offer obstetrical services; 2) hospitals in counties with higher socioeconomic status, measured by unemployment rate and percentage of the population who are white, have an increased likelihood of providing obstetrics; 3) hospital ownership has a relatively strong association with the provision of obstetrical services; and 4) the same characteristics that predict a hospital has obstetrical services do a poor job at predicting which hospitals do not offer those services. These results encourage researchers to examine areas where hospitals do not provide obstetrical care, and to investigate the dynamic between community characteristics and provider and consumer behavior. This study suggests to policymakers that targeting vulnerable communities and promoting regional and alternative modes of delivering obstetrical services may be effective means to ensuring that rural women have equitable access to obstetrical care. PMID- 8366685 TI - A patient survey system to measure quality improvement: questionnaire reliability and validity. AB - This study describes the results of a four-year research effort to develop inpatient and outpatient questionnaires that have sufficient validity and reliability to be used to measure patient perceptions of quality. As part of this effort, over 50,000 inpatients, emergency room patients, and ambulatory surgery patients from over 300 hospitals representing every US census region were surveyed. Separate questionnaires, called Quality of Care Monitors, were developed for inpatients and outpatients. The inpatient questionnaire consisted of 8 scales: Physician Care, Nursing Care, Medical Outcome, Courtesy, Food Service, Comfort and Cleanliness, Admissions/Billing, and Religious Care. The outpatient questionnaire had 7 scales: Physician Care, Nursing Care, Medical Outcome, Facility Characteristics, Waiting Time, Testing Services and Registration Process. The study found strong evidence of construct validity, predictive validity, and internal consistency for both questionnaires. Each questionnaire is capable of measuring separate dimensions of patient experience. A data bank developed from these questionnaires is currently accessed regularly by participating hospitals to assess quality improvement and to make benchmark comparisons with similar hospitals. PMID- 8366686 TI - Drug information from pharmacies: desire for more spontaneous information. PMID- 8366687 TI - The important role of international exchange in the development of medical informatics in developing countries: a report from China. AB - China is a developing country, and so is inferior to the developed countries in many aspects of science and technology. It is similarly a new member in the world ranking of the application of computers in biomedicine. However, since implementing the policy of reform and opening to the outside world in 1976, China has achieved greater success in biomedical signal and image processing, biomedical data processing, computer-aided diagnosis, computerized hospital management, etc. China's development shows that international exchange and cooperation are very important for the development of medical informatics in developing countries, and the application of computers in biomedicine has progressively spread all over the world and is increasingly taking root in the hearts of the people. PMID- 8366688 TI - An algorithm for leukaemia immunophenotype pattern recognition. AB - Since leukaemia-specific leucocyte antigen has not been identified to date, the immunological diagnosis of leukaemia is achieved through the application of a wide set of monoclonal antibodies specific for surface markers on leukaemic cells. Thus, the interpretation of leukaemia immunophenotype seems to be a mathematically determined comparison of 'what we found' and 'what we know' about it. The objective of this study was to establish an algorithm for transformation of empirical rules into mathematical values to achieve proper decisions. Recognition of leukaemia phenotype was performed by comparison of phenotyping data with reference data, followed by scoring of such comparisons. Systematic scoring resulted in the formation of new numerical variables allocated to each state, whereas a most significant variable was described as a complex measure of compatibility. A system of recognized states was described by mathematical variables measuring the confidence of information systems, i.e. maximal, total and relative entropy. The entire algorithm was derived by matrix algebra and coded in a high-level program language. The list of the states recognized appeared to be especially helpful in differential diagnosis, occasionally pointing to states that had not been in the scientist's mind at the start of the analysis. PMID- 8366689 TI - A database manager of biomedical images. AB - In order to allow an efficient archiving and retrieval of biomedical images, PACS would include an image DBMS. As biomedical images have complex structures we developed a specific DBMS over a relational one. The medical image database manager ensures a data description that takes into account data semantics so that consistency or existential constraints may be verified. It provides a unique language to retrieve images no matter what their storage format. It encompasses the queries of the user which constitute a filter over associated data. The manager can handle changes in the environment of the image. We implemented a manager prototype to show the validity of logical access possibilities. The user need no longer know the structure of the image database to access data. The logical access allows retrieval of images, whatever the architecture of the base. An automatic query construction consists of three functional levels including the interfaces towards the external environment which ensure a logical independence from the database, a query generator which creates the correspondence between the user's query and physical access queries, a dictionary which contains the structure of the image data and consistency constraints. PMID- 8366690 TI - Dictionary-based medical image I/O. AB - A general-purpose image I/O library is presented, whose properties derive from externally defined data dictionaries. The library has primarily been developed for image I/O in a medical image processing environment. It hence addresses all issues found in this field such as a variety of pixel types, architecture independence, automatic type conversion, and an unlimited number of image parameters. The data access routines in the library automatically convert the data types when needed. By redefining the data dictionaries, the I/O library can be tuned for other application areas. Explicit support for image compression is provided. The library is written in C++, and is available for interested parties. PMID- 8366691 TI - Data structure and computer program for fast interactive searches of clinical diagnoses. AB - Since 1987 the IDC codes of all diagnoses of patients treated in our hospital are stored in a patient-oriented (upright) database. In order to facilitate interactive searches for specific diagnoses and their combinations this database has been inverted into a data structure sorted by diagnoses. The report presented describes the data structure and the functionality of a computer program that allows very fast searches for complex combinations of diagnoses. PMID- 8366692 TI - Comparison between manual and automatic coding of medical record statistical cards at a university hospital. AB - The coding error rate of systems for medical record statistical cards (MRSCs) throughout health services is about 30%. A program using automatic coding has been developed at the Institute of Clinical Surgery II, Padua University Hospital, with a view to reducing this percentage. Out of an overall sample of 4776 MRSCs from all departments of the hospital, 54 were automatically coded at our institute. Categories of discrepancy between the discharge diagnosis codes of the 4722 manually coded MRSCs and the other 54 MRSCs were classified as follows: types I-III, diagnosis assigned to an erroneous under-class, class or heading (ICD-9) respectively; type IV, incorrect diagnosis formulation precluding code assignment; type V, two or more discrepancies on MRSC; and type VI, secondary diagnosis not coded. Discrepancy rates were as follows: 22.3% and 0.0% for type I; 21.3% and 0.0% for type II; 17.6% and 0.0% for type III; 1.9% and 0.0% for type IV; 5.8% and 0.0% for type V; 31% and 1.9% for type VI. Code discrepancy rates for surgical procedures, which were also compared, ranged from 7.0 to 12.5% for manual coding, while no discrepancy was observed in automatically-coded MRSCs. The results clearly demonstrate the utility of the system reported on, and it is suggested that it should be used in a modified form in other hospital departments. PMID- 8366693 TI - Genealogy data design appropriate for family relationship retrieving. AB - Data structure representing a genealogy or genealogies as a stand-alone date structure is presented. Genealogy is considered as a finite, connected graph with nodes ni representing individuals, arcs (ni, nj), ordered pairs of nodes as parent-offspring relationships and edges (ni, nj), unordered pairs of nodes as twinships. Such structure enables storage of the minimum of family relationships and recognition of them and others like 'ancestor-descendant', 'sibs', 'twins', 'cousins', 'uncle/aunt-nephew/niece' or 'spouses'. Algorithms for genealogy retrieval are classified as vertical, lateral and parallel. In certain combinations, vertical and lateral algorithms become capable of finding any relatives, no matter if they are in a direct 'ancestor-descendant' relationship or if they have only the same ancestor(s). A parallel algorithm is designed in order to search for twins, triplets etc. PMID- 8366694 TI - Approaches to the construction of a medical informatics glossary and thesaurus. AB - In a project concerned with establishing a glossary and thesaurus for the medical informatics domain, various approaches to the task have been investigated. The developers take the view that a glossary should be a coherent system of terms, reflecting a coherent system of concepts that underlies a body of knowledge about a domain. A framework for the conceptual analysis of the concepts/terms underlying the domain has been developed. The emphasis of this framework is on how the concepts relate together. This work has given an important insight into how the practical task of establishing well-structured vocabularies for a field can be better achieved. An eclectic approach to term selection was adopted. Criteria for assessing what constitutes good definitions for concepts in a field were examined. Using all these approaches glossaries, thesauri and domain models of the medical informatics field are being developed. Another aspect of our work of particular interest is the development of attributed definitions from which inheritance patterns can be defined. PMID- 8366696 TI - [External medical audit]. PMID- 8366695 TI - [A new Dutch analysis illuminates euthanasia without request]. PMID- 8366697 TI - ["Fair" research funds and the other ones. How should the distribution of the grants be ruled?]. PMID- 8366698 TI - [Separate accident and emergency departments!]. PMID- 8366699 TI - [Harmony at medical meetings]. PMID- 8366700 TI - [Better support for the Baltic countries]. PMID- 8366701 TI - [Strong arguments against euthanasia]. PMID- 8366702 TI - [Confusion of concepts in the report on alcoholism]. PMID- 8366704 TI - [Violence at health services--lack of motivation]. PMID- 8366703 TI - [Professional education of teachers]. PMID- 8366705 TI - [Atherosclerosis--an autoimmune disease?]. PMID- 8366706 TI - [Analgesics in acute abdominal pain. Categorical prohibition is absurd]. PMID- 8366707 TI - [Pain relief in cases of acute abdomen. Time to reconsider?]. PMID- 8366708 TI - [Prenatal ultrasonic diagnosis. A valuable screening with low number of false findings]. PMID- 8366709 TI - [A 10-year perspective on isotretinoin therapy. Dramatic improvement in severe acne]. PMID- 8366710 TI - [First cases of hepatitis E diagnosed in Sweden]. PMID- 8366711 TI - [Oral tetracycline--treatment of acne. Rapid facial improvement, but back lesions are more difficult to treat]. PMID- 8366712 TI - [Costs of stroke care. Lower costs in spite of increased incidence]. PMID- 8366713 TI - [Mussels filtrate for circulation in the sea. Control and choice of places of cultivation protect against marine biotoxins]. PMID- 8366714 TI - [Physiopathology of mitochondria. From Luft's disease to aging and diabetes]. AB - The first disease due to disturbances in a cell organelle was discovered in 1959 62, and its basis was loose-coupling of oxidative phosphorylation in the skeletal muscle mitochondria accompanied by severe alterations of their structure (Luft's disease). During the 1980s, functional disturbances and structural alterations in the mitochondria were observed in more than 100 disease entities, mainly in parts of the central nervous system and skeletal muscles. A second breakthrough in this area was the discovery in 1963-64 that mitochondria had their own DNA, mtDNA. Following the observation in 1988 of mutations of mtDNA in mitochondrial diseases, such mutations--mainly deletions and point mutations--were observed in almost all mitochondrial diseases. A remarkable extension of the area is the notion that "normal" ageing is accompanied by decreased oxidative phosphorylation and the appearance of mtDNA mutations. During the last two years, such changes have been demonstrated in diseased states in tissues and organs, which are especially reliant on oxygen supply: in the central nervous system (Parkinson's disease, some types of epilepsy and seizures, Huntington's disease, possibly also in Alzheimer's disease); in heart muscle (cardiomyopathies) and in skeletal muscle. Type 2 diabetes or NIDDM engages two tissues most reliant on oxygen consumption, the pancreatic islets (insulin secretion) and skeletal muscle (insulin sensitivity). Both these functions are genetically determined, the latter to a high degree also controlled by "environmental" factors. The evident age factor in the development of NIDDM could be on a par with the "normal" ageing process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366715 TI - [Refer emergency cases directly to the specialist! Un-economical with inexperienced physicians in primary health care]. PMID- 8366717 TI - [Realistic occupational health services]. PMID- 8366716 TI - [Control of oral anticoagulant therapy. The Quick method is one step back]. PMID- 8366718 TI - [The law for protection against infectious diseases and HIV: differentiate between the law and the person]. PMID- 8366719 TI - [The psychodynamic movement should choose its direction!]. PMID- 8366720 TI - [Facilitate nose breathing during skiing]. PMID- 8366721 TI - [Which health care ideology? In defense of the small hospitals]. PMID- 8366722 TI - [Prohibition of nickel use within the EEC. Sweden directs the standardization work to reduce the risk of allergy]. PMID- 8366723 TI - [Reduced blood pressure and myocardial infarction. Does therapy increase the risk of coronary disease?]. PMID- 8366724 TI - [Future treatment of stroke. Brain damage in stroke can be reduced by drugs]. PMID- 8366725 TI - [Better results for children than for adults. 10-year experience with kidney transplantation in children]. PMID- 8366726 TI - [Physicians' assessments of disabilities scrutinized. Criticism does not justify further investigation]. PMID- 8366727 TI - [Intraoperative determination of intact parathyroid hormone. An aid for the surgeon in primary hyperparathyroidism]. PMID- 8366728 TI - [From MBD to ADHD--and then? A literature review on a controversial diagnosis]. PMID- 8366729 TI - [Sarcoidosis from a new pulmonary perspective. Do antigenic peptides cause the inflammation?]. PMID- 8366730 TI - [Caesar Boeck and Jorgen Schaumann. The men behind the sarcoidosis syndrome]. PMID- 8366731 TI - [Enterobiasis in preschool children. Every fourth child is infected]. PMID- 8366732 TI - [Arthroscopy of the shoulder joint. Technique, indications, surgery and complications]. AB - Diagnostic and operative arthroscopy of the shoulder joint has gained considerable importance in traumatology and orthopedic surgery over the last years. Injuries of the limbus glenoidalis, in particular traumatic shoulder luxation, injuries of the rotator cuff, infection of the glenohumeral joint and unclear posttraumatic pain are indications for diagnostic and operative arthroscopy. Arthroscopy of the shoulder is a procedure, which offers exact diagnosis and the possibility of immediate surgery at the same time. The technique of the shoulder joint arthroscopy has to be carried out carefully and according to a standard protocol. The complication rate of around 5% of shoulder arthroscopy has not to be neglected. PMID- 8366733 TI - [Genesis and treatment of hand para-articular, painful tendon and tendon sheath changes]. AB - Many patients suffer from wrist disorders caused by tendon- and tendon-sheath affections. Apart from this the successful treatment of these affections is an important implication concerning national economy. In Lower Saxony 2.3% of all RVO-insured patients have these disorders. Most tendon- and tendon-sheath affections are due to chronic stress which is generally treated by a non operative therapy. Only some need be treated by a surgical intervention. In this paper the most frequent painful tendon- and tendon-sheath-diseases are listed, their clinical appearance is shown and the different methods of treatment are discussed. PMID- 8366734 TI - [Inguinal recurrence after therapeutic lymphadenectomy in malignant melanoma]. AB - In a retrospective study, 73 stage-II melanoma patients with 22 superficial and 51 deep groin dissections were observed over a maximum of 9 years of follow up (median 67.5 months). The 5-year survival rate of 29.8% was consistent with that yielded by comparable analyses of other investigators. However, the probability of recurrence in the node dissection field was as high as 35%. All groin recurrences occurred in the first 29 months after lymph node clearance (median 6 months). Patients with groin recurrence following lymph-node dissection had a poor prognosis (median survival 12 months). In a multifactorial analysis (Cox model), the only prognostic factor of probability of recurrence was the development of regional in-transit cutaneous metastases (p = 0.0028). Factors that did not affect the appearance of recurrent metastases in the node dissection field were: site of primary melanoma, tumor thickness, epidermal ulceration, degree of lymph node involvement (p = 0.2) age, sex, degree of surgery (superficial or deep groin dissection) and adjuvant chemotherapy. Because regional in-transit cutaneous metastases mostly occur synchronously with groin recurrence or later, they are a typical concomitant phenomenon rather than a prognostic factor of recurrence. PMID- 8366735 TI - [Measuring impedance for evaluating ischemia damage to the human liver in preparation for transplantation]. AB - In 22 human donor livers the measurement of the non-invasive bioelectrical impedance was performed prospectively to evaluate the degree of tissue damage sustained during cold ischemia. The results of the measurement were correlated with liver function, the method of organ preservation and the period of ischemia. The impedance was measured in vivo as 620 ohm (at 192 Hz), the phase angle as 7.4 degrees (at 5 kHz). The results were compared with the data obtained from 72 patients who underwent elective laparotomies. The 22 donor livers were studied further during ischemia. The method was found to be a reliable way of detecting severe damage to the hepatocytes during the cold ischemia. PMID- 8366736 TI - [Intestinal motility after jejunum interposition and Roux-Y reconstruction--an animal experiment study]. AB - An experimental study in animals was conducted to evaluate the motility patterns after total gastrectomy. Eight male beagle dogs (22.5-27.2 kg) had total gastrectomy with standardized designs of gastric substitution: (1) jejunal interposition (JI, n = 4); (2) Roux-en-Y reconstruction (RY, n = 4). Motility patterns were detected with perfused manometry (eight measuring ports), sequential scintigraphic emptying studies of the gastric substitute (caloric and acaloric medium viscosity test meals), and a hydrogen breath test with lactulose. The preoperative studies of the same individuals served as controls (CO). To detect postgastrectomy adaptation processes the postoperative studies were conducted 6-8, 12-14, and 24-30 weeks after total gastrectomy. The emptying of the gastric substitutes was markedly accelerated compared with CO after 6 months (T50: 5.8-8.1 min). In contrast to the preoperative studies, caloric test meals caused a trend to increase the velocity of the evacuation. The intestinal transit time was accelerated too in the weeks immediately, after the operation. In JI dogs intestinal transit was then markedly slowed and led to a highly significant difference after 6 months compared to RY animals (CO: 101 +/- 26min, JI: 104 +/- 18.2min, RY: 71.3 +/- 13.4min; p < 0.01). Pathologic motility patterns could be identified as the cause of this observations: RY dogs showed a marked increase of the intestinal motility index in the proximal jejunum (p < 0.0001) and a dissociation between the motility patterns of the duodenum and the gastric substitute. The observations gave rise for the supposition that this parts of the small bowel might generate two independent pacemarkers that both influence the lower intestinal parts after RY reconstruction. We conclude that the motility patterns of the entire small bowel highly influence the postoperative function of reconstruction procedures after total gastrectomy. The emptying velocity of the jejunal gastric substitute does not seem to have a major influence on the postoperative results. According to motility patterns jejunal interposition has a better outcome than Roux-en-Y reconstruction. PMID- 8366737 TI - [Pneumatosis cystoides intestinii]. AB - Pneumatosis cystoides intestinalis (PCI), a condition involving submucosal or subserosal gas-containing cysts of the wall of the gastrointestinal tract, is a rare entity. It is mostly diagnosed between the third and fifth decades of life without a clear sexual predominance. Different aetiopathogenetic factors are under discussion, the most probable being a bacteriologic cause (Clostridium perfringens) in combination with minimal leaks in the mucosal barrier. There are no pathognomonic symptoms; the clinical picture ranges from incidental findings to haematochezia. Diagnosis is based on plain abdominal film and X-ray following barium enema. Methods of treatment in symptomatic cases are oxygen and antibiotic (metronidazole) therapies and, in severe cases, resection of the diseased part of the intestine. PMID- 8366739 TI - Effects of pulsed lasers on agar model simulation of the arterial wall. AB - Coronary laser angioplasty is limited by a high rate of dissection and the occurrence of abrupt closure and perforation. The aim of this study was to visualize the mechanical effects of pulsed lasers on two chamber in vitro models. These models consisted of 1 or 2 agar layers and calcium carbonate inclusions (1 layer model) or lipid (2-layer model) simulating lipid or calcified tissue. The inclusions were irradiated with a holmium-yttrium-aluminum-garnet (Ho-YAG) laser or a xenon chloride excimer laser. The Ho-YAG laser demonstrated dissection-like expansions of the target and perforation-like cracks. The size of dissection was obtained using an the empirical formula of energy (E) and the maximal expansion distance (Dmax) of the targets, Dmax = 0.15E0,87-1,17. The excimer laser showed rare and short perforation-like cracks and little dissection-like expansion of the gaseous products originating from the ablation of material. Ho-YAG laser ablation is likely to induce target tissue dissections and/or perforations. Excimer laser-ablates targets with less traumatic effects than Ho-YAG laser. PMID- 8366738 TI - Beta-carotene enhances plaque detection by fluorescence attenuation in an atherosclerotic rabbit model. AB - Improved detection of plaque during cardiovascular procedures could enhance the outcome of diagnosis and therapy. We evaluated a new method to stain plaque using a special intravenous preparation of beta-carotene (beta-C) in an in vivo model. beta-C was used to enhance the absorption coefficient of plaque and decrease the laser-induced fluorescence emission. Using this approach the difference in fluorescence emission was accentuated between normal artery and atherosclerotic plaque. Twenty-nine NZW rabbits were divided into five groups, each receiving a different intervention. This included the administration of beta-C to rabbits on a normal or a high cholesterol diet, with or without endothelial debridement. Aortae were examined grossly, by histology, and relative total fluorescence was detected at 886 sites using 488 nm or 514 nm laser excitation. At 488 nm excitation, unstained plaque attenuated total fluorescence twice as much as normal controls (7.55 +/- 1.46 vs. 15.06 +/- 3.12; P < 0.0001); beta-C stained plaque attenuated total fluorescence 17 times more than normal controls (0.89 +/- 0.29 vs. 15.06 +/- 3.12; P < 0.0001). Total fluorescence from unstained plaque was eight times greater than plaque stained with beta-C (7.55 +/- 1.46 vs. 0.89 +/- 0.29; P < 0.0001). Results obtained using 514 nm excitation were similar. The attenuation effect persisted up to 8 weeks following beta-C administration. Thus, beta-C stained plaque displayed fluorescence attenuation, which suggests that pretreatment with beta-C may greatly enhance plaque detection. This may be useful as a guide during plaque removal procedures. PMID- 8366740 TI - Acute response of the arterial wall to pulsed laser irradiation. AB - This study was designed to examine the acute response of normal arterial wall to pulsed laser irradiation. Irradiation with an Excimer or a Holmium YAG laser was performed in 15 normal iliac sites of 8 male New Zealand white rabbits. The excimer laser was operated at 308 nm, 25 Hz, 50 mJ/mm2/pulse, and 135 nsec/pulse and the Ho:YAG laser was operated at 2.1 microns, 3.5 Hz, 400 mJ/pulse, 250 microseconds/pulse. The excimer and Ho:YAG laser were coupled into a multifiber wire-guided catheter of 1.4 and 1.5 mm diameter, respectively. The mean luminal diameter increased similarly from 2.01 +/- 0.29 to 2.46 +/- 0.27 mm (P < 0.0005) and from 2.09 +/- 0.53 to 2.45 +/- 0.30 mm (P < 0.005) after excimer and Ho:YAG laser irradiation, respectively. Perforation occurred in 3 of 15 Ho:YAG irradiated sites and 0 of 15 excimer laser irradiated sites. The sites irradiated with excimer or Ho:YAG laser had similar histologic features, consisting of shedding of the endothelium, disorganization of internal elastic lamina, localized necrosis of vascular smooth muscle cells, and fissures in the medial layer. However, the sites irradiated with excimer laser had lower grading scores than those irradiated with the Ho:YAG laser (P < 0.05). Irradiation with excimer or Ho:YAG laser of normal arteries results in: (1) vasodilation of the irradiated artery; (2) localized mechanical vascular injury, and (3) Ho:YAG laser induces more severe damage to the arterial wall than excimer. PMID- 8366742 TI - Primary closure of choledochotomy using CO2 laser: comparison with suture closure. AB - This study was designed to compare laser welding to suture closure of the common bile duct (CBD). A 12 mm linear choledochotomy was closed in 12 mongrel dogs using tissue welding low-energy CO2 laser. Tissue welding was accomplished at 5.0 w/cm2 for 120 sec. Twelve similar mongrel dogs (control) were treated with CBD closure using 5/0 Vicryl (polyglactin 910, Ethicon, Inc., Somerville, NJ) interrupted simple stitches. All animals were sacrificed at six weeks. Gross and histologic evaluation of the choledochotomy site were performed. There were no statistical differences in parameters of comparison in the two groups. These parameters were pre- and post-treatment measurements of liver function tests, stenosis, and dehiscence. However, it must be noted that there was a 33% (4/12) incidence of dehiscence and death in the CO2 laser welded choledochorrhaphy. This result, although not statistically significant, is clinically significant. We conclude that the tensile strength of CO2 laser welded CBDs must be optimized and that these results are preliminary and still unreliable to recommend for clinical adaptability. PMID- 8366741 TI - In vitro decalcification of aortic valve leaflets with the Er:YSGG laser, Ho:YAG laser, and the Cavitron ultrasound surgical aspirator. AB - This study was designed to compare the efficacy of the erbium:yttrium-scandium gallium-garnet (Er:YSGG) laser and the holmium:yttrium-aluminum-garnet (Ho:YAG) lasers in debriding calcium from freshly explanted aortic valve leaflets and to compare the Er:YSGG laser with the Cavitron ultrasonic surgical aspirator (CUSA). Aortic valve leaflets were freshly explanted from patients undergoing aortic valve replacement for aortic stenosis. Initially, 4 leaflets each were debrided with the Er:YSGG and the Ho:YAG lasers to attempt removal of calcium deposits while preserving the underlying integrity of the leaflets and minimizing thermal damage. The Er:YSGG laser was more effective in doing so with less thermal and photoacoustic damage when compared with the Ho:YAG laser. Twelve more leaflets each were then debrided with the Er:YSGG laser and the CUSA. The Er:YSGG laser again proved less injurious to the underlying leaflet. The CUSA-treated leaflets demonstrated shattering and disruption of adjacent tissue as well as collagen fiber exposure. These changes were not seen with the Er:YSGG laser. Because of these properties, the Er:YSGG laser merits further evaluation as a tool for aortic valvuloplasty procedures in selected patients with senescent calcific aortic stenosis. PMID- 8366743 TI - Tumor specific response to photodynamic therapy. AB - The exact mechanism by which photodynamic therapy (PDT) causes tumor destruction has not been elucidated. Early reports indicated that PDT causes direct cellular effects probably mediated by unstable oxygen species, resulting in cellular oxidation and death. More recently, PDT effects on tumor blood flow have been implicated, and there are questions as to whether the PDT response is specific to tumor tissue. Rats were implanted with a window chamber containing either a mammary adenocarcinoma or a piece of inert surgical sponge. After growth of the tumor was ascertained, all rats were given 5 mg/kg Photofrin intraperitoneally, and then were irradiated with 630 nm light 24 hours post-injection. Caliper thickness and reflectance measurements were performed before and after irradiation; all animals were sacrificed 72 hours post-PDT and the chambers submitted for histologic analysis. Animals implanted with tumors demonstrated marked edema of the chamber with an associated decrease in reflectance. No edema response was noted in the chambers containing inert sponge, or in any controls. Nonselective PDT effects (characterized by a marked foreign body response) in chambers containing sponge was not seen. Histologic analysis of treated specimens corroborate the above data. PMID- 8366745 TI - Slit lamp laser Doppler interferometer. AB - A slit lamp laser interferometer is described for clinical in vivo eye length measurements. The basic components are a laser Doppler interferometer, a slit lamp attachment, and a commercial slit lamp. First measurements of the axial length of the eye yielded a standard deviation of 0.04 mm and less. PMID- 8366744 TI - Effects of pulse width on erbium:YAG laser photothermal trabecular ablation (LTA). AB - An erbium (Er):YAG laser can remove trabecular meshwork (TM) by photothermal ablation with minimal contiguous thermal damage. A variable pulse width Er:YAG laser was used to investigate the effect of varying pulse width on ablation of human TM. Trabecular photothermal ablation was performed on tissue obtained from eye bank eyes at pulse widths of 50, 150, and 250 microseconds, with energy held constant at 4 mJ. At this energy, a single laser pulse was sufficient for full thickness ablation of TM. Laser energy was delivered through a 200-microns diameter optical fiber held in apposition to the tissue sample, which was immersed in physiologic saline. High-speed photography of the resultant steam bubbles also was performed. Light microscopy and scanning electron microscopy of TM ablated at 50 microseconds revealed the greatest variability in size (0-140 microns) of the full-thickness ablated areas and demonstrated blast effects, tissue shredding and < or = 10 microns thermal damage. At 150 microseconds, the full-thickness ablated areas were more consistent size (115-120 microns), showed no blast effects and 10 to 20 microns thermal damage. At 250 microseconds, the largest ablations were found (180-220 microns) and showed no blast damage; however, a significant amount of thermal damage (< or = 50 microns) was evident. The steam bubbles produced by the laser energy were largest at 50 microseconds and did not begin to collapse until well over twice the original pulse interval. At 150 and 250 microseconds, the steam bubbles were successively smaller and dissipated at the end of the laser pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366746 TI - Changes in oxidative metabolism of murine spleen following laser and superluminous diode (660-950 nm) irradiation: effects of cellular composition and radiation parameters. AB - Chemiluminescence (CL) of splenocytes of A/Sn mice was recorded after irradiation of the cells with various individual laser an superluminous diode probes at wavelengths from 660 to 950 nm (pulse repetition rates varying from 4 to 5,000 Hz) and at various doses. Laser radiation was found to increase or suppress the spontaneous CL of splenocytes suspension, the amplitude and the sign of the effect depending on the cellular composition of the samples. Direct correlations between the effect of laser radiation (per cent in changes of CL when irradiated at 820 nm, 1.1 x 10(3) J/m2, 292 Hz) and per cent of plasmacytes (r = 0.743, P < 0.001), neutrophils (r = 0.650, P < 0.001) as well as myelocytes and metamyelocytes (r = 0.505, P < 0.01) were established. The correlation with per cent of lymphocytes (r = -0.590, P < 0.001) was found to be a reverse one. Dependence of the irradiation effects on dose, pulse repetition rate, and wavelength are presented. PMID- 8366748 TI - Studies of acoustical and shock waves in the pulsed laser ablation of biotissue. AB - Quantitative studies are conducted into the absolute pressure values of the acoustical and shock waves generated and propagating in a biotissue under pulsed (tau p = 50 ns) UV (lambda = 308 nm) laser irradiation (below and above the ablation threshold). Powerful (several hundreds of bars in pressure) high frequency (f approximately 10(7) Hz) acoustic compression and rarefaction pulses are found to be generated in the biotissue. The amplitudes and profiles of the acoustic pulses developing in atherosclerotic human aorta tissues and an aqueous CuCl2 solution under laser irradiation are investigated as a function of the laser pulse energy fluence. The results obtained point to the absence of the cold spallation of the objects of study by rarefaction waves. Based on experimental data, the rise rates, pressure gradients, and propagation velocities of shock waves in the biotissue are calculated. The experimental data are found to agree well with the theoretical estimates. PMID- 8366747 TI - Analgesic effect of Ga-Al-As diode laser irradiation on hyperalgesia in carrageenin-induced inflammation. AB - This study concerned the effect of Ga-Al-As diode laser irradiation (780 nm, continuous wave, 31.8 J/s/cm2, spot size od 0.2 mm, 3 minutes/dose) on hyperalgesia induced in the hind paw of rats by injecting carrageenin. The pressure-pain thresholds of hind paws were measured by the Randall-Selitto test for evaluation of hyperalgesia. Two doses of laser irradiation, given to the inflamed region immediately before and after the injection of carrageenin, partially (approximately 50%) inhibited the occurrence of hyperalgesia accompanied with a progression of inflammation. This analgesic effect was equal to that of indomethacin (4 mg/kg, i.o.). In another group, the hyperalgesia was removed almost completely for at least 24 hours by one dose of laser irradiation, which was given 3 hours after the carrageenin injection, whereas the edema was not inhibited. This analgesic effect, however, was partially (approximately 50%) antagonized with a dose of 10 mg/kg (i.p.) of naloxone and totally inhibited with 30 mg/kg. These results suggest that low-power laser irradiation on inflamed regions of carrageenin-treated rats has a marked analgesic effect and that certain mechanisms that are not related to endogenous opioids are involved in a part of the mechanisms of the analgesic effects. PMID- 8366749 TI - [Gastroenterologic endoscopy--where does the future lie?]. PMID- 8366750 TI - [Molecular biology: applications in hepato-gastroenterology]. AB - Recombinant DNA technology is of increasing significance for the diagnosis, therapy and prevention of human diseases. The principle of recombinant DNA technology is illustrated and the clinical applications in hepatology and gastroenterology are discussed. PMID- 8366752 TI - [Echinococcosis--current status of diagnosis and therapy]. AB - The most frequent parasitosis in Europe is the infection by Echinococcus spp. Echinococcus granulosus is identified worldwide, 60% of all human infection are found in the liver, where cysts (hydatides) are built. Echinococcus alveolaris is found in the northern hemisphere, endemic in Middle Europe in Southern Germany, Austria and parts of Switzerland. 98% of all human infection are localized in the liver, where infiltrative growth destroying the tissue is found. Diagnosis is based on serological techniques, ultrasound and CT-scanning. Surgery is the only curative therapy by resection of cystic areas followed by chemotherapy with Mebendazole. In studies Albendazole has shown better results. CT-guided percutaneous drainage followed by instillation of hypertonic saline is performed in case of non-resectable hydatidosis. PMID- 8366751 TI - [Gastroenterologic-endoscopic studies in ambulatory practice. Spectrum of applications, trends, quality and economic aspects]. AB - A review on spectrum, frequency and complication rate of gastroenterological endoscopy in ambulant practice is given based on data of the National Association of Public Health Insurance Physicians of Germany. The following important aspects are mentioned: 1. Endoscopy has surpassed radiology in diagnostic examinations for gastric and colonic diseases. 2. Gastroscopy is more commonly carried out by physicians, coloscopy by gastroenterologists or specialists. Hospital doctors don't contribute significantly to ambulant endoscopic examinations of stomach and colon. 3. Endoscopic examinations of the pancreas, biliary tree, laparoscopy and other techniques play an insignificant role in ambulant practice. 4. The complication rate of ambulant gastroenterological endoscopy is very low. There have been only a few malpractice cases due to complications of gastroenterological endoscopic examinations. 5. The quality of coloscopy is not yet satisfactory as measured by the relative proportions of partial and total coloscopy. 6. In the past only limited attention was given to aspects of quality assurance and quality control in endoscopy in ambulant practice. This should be changed in the future. 7. The fees for gastroscopy and coloscopy allowed by the public insurance companies don't cover the expenses and are inadequate. As a result, a negative impact on the quality of medical care can be expected. PMID- 8366753 TI - [Ergotamine-induced rectal stenosis in a patient with long-term migraine]. AB - A 36 year old woman was admitted to our hospital for treatment of a high-grade rectal stenosis of unknown origin. She had a history of migraine going back 10 years. On intensive questioning she admitted using up to 5 ergotamine-containing suppositories a day. On the basis of history and clinical investigations the rectal stenosis must be connected with the abuse of ergotamine-containing suppositories. This case demonstrates that patients with an unexplained rectal syndrome should be asked for analgetics-containing suppositories specifically. Only discontinuation of treatment in time can preserve the patient from development of a rectal stenosis. In case of a rectal stenosis surgical treatment can be avoided by means of endoscopic controlled dilatation. PMID- 8366754 TI - [Extracorporeal shock wave lithotripsy of an impacted gallstone in cholecysto antral fistula]. AB - The endoscopic examination of a patient with gastrointestinal bleeding unexpectedly revealed a cholecysto-antral fistula with incipient penetration of a gallstone into the stomach (and presumably intermittent bleeding from the fistula rim). As endoscopic extraction was not possible and the stone impacted in the fistula was visible in the ultrasound scan extracorporeal shock-wave lithotripsy was carried out. An electrohydraulic lithotripter was used and 1,913 shock waves were applied at a maximum of 26,000 volts. In a single treatment session the stone was disintegrated completely into fragments small enough for spontaneous elimination. No sedative or analgesic medication was required. There was no evidence of any complications or side-effects following the ESWL. PMID- 8366755 TI - [11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET. AB - The in vivo behavior of the stereoisomers of [11C]McN5652, a highly potent serotonin (5-HT) uptake blocker, was determined to evaluate their utility as radiotracers for imaging 5-HT uptake sites by positron emission tomography (PET). After intravenous injection into mice, [11C](+)McN5652 showed markedly higher uptake and longer retention in regions with high density of 5-HT uptake sites than the [11C]-labeled racemic mixture, while [11C](-)McN5652 washed out rapidly. With the [11C](+)-enantiomer, the ratio between hypothalamus and cerebellum reached 6 at 90 minutes. The binding of [11C](+)McN5652 was inhibited by 45-73% by pre-injection of 5 mg/kg of paroxetine, a selective 5-HT uptake blocker, in all regions examined except cerebellum where no significant effect of the drug was observed. [11C](-)McN5652 showed no specific binding in any of the regions. The [11C]-labeled cis isomer, [11C]McN5655, revealed surprisingly low brain penetration and showed no significantly higher uptake in regions of interest than cerebellum. These results suggest that [11C](+)McN5652 is a promising candidate as a PET radiotracer for studying 5-HT uptake sites in vivo. PMID- 8366756 TI - Effect of OP-41483.alpha-CD, a prostacyclin analog, on a clamp-induced endothelial injury in rats. AB - We studied the effect of OP-41483.alpha-CD, a stable prostacyclin analog, on clamp-induced endothelial injury in rats. The injury was assessed by vascular Evans blue leakage and using a scanning electron microscope. OP-41483.alpha-CD significantly reduced the Evans blue leakage at doses of 30 and 100 ng/kg/min. PGE1.CD was also found to show an equipotent inhibitory action on the dye leakage. From scanning electron microscopic observations, a moderate degree of intimal defects, microvillous projections and platelet adhesions at the luminal surface were seen in the specimens from OP-41483.alpha-CD (30 and 100 ng/kg/min) treated rats. Furthermore, OP-41483.alpha-CD, PGE1.CD and Dibutyryl cyclic AMP (DbcAMP) were found to accelerate a proliferation of cultured bovine endothelial cells in a dose-dependent manner in vitro. Taken together, these data indicate that the endothelial regenerative effect of OP-41483.alpha-CD could contribute to healing of clamp-induced endothelial injury and it may be an important therapeutic drug to protect vascular intimal injury. PMID- 8366757 TI - Conjugation of phenylacetic acid and m- and p-hydroxyphenylacetic acids in the rat striatum. AB - Two factors that might regulate the levels of the trace acids, phenylacetic acid (PAA), m-hydroxyphenylacetic acid (mHPAA) and p-hydroxyphenylacetic acid (pHPAA) in the rat striatum were investigated: first, formation of conjugates of these acids and second, transport out of the brain by a probenecid-sensitive system. The presence of conjugates of these acids was investigated by subjecting homogenates of rat striatum to hydrolysis. The concentrations of PAA were increased ten-fold by hydrolysis, pHPAA increased two-fold, and mHPAA was unaffected. These findings coupled with the failure of parglyline to decrease free or total PAA levels suggest that conjugation of PAA is an important factor regulating free PAA levels. The transport inhibitor, probenecid, increased the concentrations of free mHPAA, free pHPAA and the total concentrations of all three acids indicating that all three trace acids can be removed from the rat brain by a transport system. PMID- 8366758 TI - Possible transsynaptic cholinergic neuromodulation by ATP released from ileal longitudinal muscles of guinea pigs. AB - The effects of alpha, beta-methylene ATP (alpha, beta-mATP) and beta, gamma methylene ATP (beta, gamma-mATP) on endogenous acetylcholine (ACh) release evoked by electrical nerve stimulation were evaluated in guinea-pig ileal longitudinal muscles. Release of ACh was measured with an HPLC-electrochemical detector system and release of ATP by luciferin-luciferase assay. Electrically evoked endogenous ACh release was reduced by both alpha, beta-mATP and beta, gamma-mATP at concentrations of 3 and 30 microM. The inhibitory effect of alpha, beta-mATP (30 microM) on ACh release was not detectable in the presence of theophylline (100 microM), a P1-purinoceptor antagonist, that itself enhanced ATP release. When exogenous ATP (0.1 microM) was added to the bath in which the ileal segment was suspended, it was rapidly metabolized, presumably by ecto-ATPase, and disappeared from the medium within 15 min. At 30 microM, alpha, beta-mATP induced ATP release in a suramin-sensitive but Ca(2+)- and atropine-insensitive manner, suggesting P2 receptor-mediated release of ATP from the smooth muscle. We conclude from these findings that alpha, beta-mATP and, probably, also beta, gamma-mATP, do not reduce ACh release by direct stimulation of presynaptic P1-purinoceptors, and that endogenous ATP released postjunctionally by these ATP analogs is decomposed metabolically to adenosine in the synapse and this adenosine triggers P1 purinoceptor sensitive neuromodulation of cholinergic transmission. PMID- 8366760 TI - Pharmacological characterization of Abbott-81282, a novel, non-peptide angiotensin-II antagonist selective for type-1 receptors. AB - Abbott-81282 (A-81282) has been identified among a series of related compounds as being a highly potent and selective antagonist of angiotensin receptors. At AT1 receptors of the rabbit aorta, A-81282 exhibited a pA2 of 9.64 (+/- 0.33) vs. angiotensin-II, and demonstrated characteristics consistent with competitive antagonism of this receptor. These results were supported in radioligand binding assays in which A-81282 inhibited the binding of [125I]-Sar-Il8-Angiotensin-II to rat liver membranes with a pKI of 8.505 (+/- 0.102). Selectivity of this agent for AT1 receptors was validated by its lack of activity at other receptor sites, such as alpha 1 receptors of isolated rabbit aorta. Moreover, A-81282 lacked affinity for AT2 receptors of bovine cerebellar membranes or for alpha or beta adrenergic receptor sites in radioligand binding assays. A-81282 lowered blood pressure significantly in vivo in renal artery-ligated rats at doses of 1 mg/kg i.v. or 5 mg/kg p.o. The compound was slowly and moderately absorbed from the duodenum of anesthetized rats and demonstrated low first-pass metabolism in the rat liver. Because of its selectivity and potency for antagonizing AT1 receptors, and its activity in lowering blood pressure in experimental animals, A-81282 has the potential to be a useful antihypertensive agent in man. PMID- 8366759 TI - Paroxetine binding in the blood platelets of post-traumatic stress disorder patients. AB - Platelet serotonin (5-HT) uptake, as determined by 3H-paroxetine (PA) binding, was studied in 20 Post-traumatic Stress Disorder (PTSD) patients and 20 normal controls. Kd (an inverse measure of affinity of 3H-PA binding to uptake sites) and Bmax (maximum number of 3H-PA binding sites) of 3H-PA binding were significantly decreased in PTSD patients as compared to normal controls. However, there was no difference in Kd or Bmax between PTSD patients with and without a diagnosis of major depression. The Bmax of 3H-PA binding was negatively correlated with state dependent anxiety score whereas Kd was positively correlated with the Mississippi Scale for Combat-Related PTSD score. The role of serotonergic processes in the psychobiology of PTSD is discussed. PMID- 8366761 TI - ODC activity and polyamine levels in isolated human colonocytes. AB - Ornithine decarboxylase (ODC) is the first and often rate-limiting enzyme in polyamine biosynthesis. ODC and polyamines (putrescine, spermidine, spermine, and cadaverine) have an essential role in cell proliferation. In this study, we investigated ODC activity and the polyamine levels of normal human colonocytes isolated from the upper and lower crypt regions. We found no significant differences in ODC activity between upper and lower crypt regions (mean +/- SEM: 105 +/- 60 and 103 +/- 52 pmol CO2/mg protein/hr, respectively). This result was further substantiated by ODC immunoreactive antibody staining technique. Levels of polyamines (putrescine, spermidine, spermine, and cadaverine) were similar in the upper and lower crypt regions (mean +/- SEM; upper/lower: 79 +/- 29/79 +/- 18; 189 +/- 116/ 137 +/- 38; 174 +/- 58/204 +/- 35; and 52 +/- 10/51 +/- 10 nmol/mg protein, respectively). Acetyl-polyamines (acetyl-putrescine, acetyl spermidine, and acetyl-spermine) levels in human colonocytes showed no significant differences between upper and lower crypt regions (mean +/- SEM; U/L: 368 +/- 109/408 +/- 89, 63 +/- 22/51 +/- 12, and 39 +/- 12/41 +/- 14 nmol/mg protein, respectively). Our results suggest that in isolated normal human colonocytes, ODC activity and polyamine levels are similar in the upper and the lower crypt regions. PMID- 8366762 TI - Glibenclamide partly reverses monesin inhibition of insulin secretion, in vivo. AB - Glibenclamide, a second generation sulfonylurea, is an oral hypoglycemic drug. It seems to act mainly on the ATP-driven K(+)- channels of the beta-cells of pancreas determining insulin secretion. Because monensin, a Na+/H+ antiport, is able when administered to rats in vivo to inhibit insulin secretion, the action of glibenclamide is studied on glycemia and insulinemia to verify if it can antagonize the action of monensin. The results show that glibenclamide is able to partly reverse ionophore induced hyperglycemia and the inhibition of insulin secretion. These results might be interpreted as if glibenclamide only reverses the ATP-driven K(+)- channel dependent insulin secretion. Moreover the antagonist action of glibenclamide is slightly delayed when both drugs are administered together. The role of Na+/H+ antiport in basal insulin secretion is discussed. PMID- 8366763 TI - Implication of ATP released from atrial, but not papillary, muscle segments of guinea pig by isoproterenol and forskolin. AB - Effects of isoproterenol and forskolin, which increases intracellular cyclic AMP, on contraction and ATP release in atrial and papillary muscles of guinea pig were evaluated. In the electrically driven-left atrial muscle segments, isoproterenol and forskolin at 0.1 microM produced an ATP release coupled with a positive inotropic effect, the values of net ATP release at 5 min after these drugs being 5.20 +/- 0.59 and 5.37 +/- 0.55 nmoles/g wet weight, respectively. The forskolin evoked-ATP release was unaffected by prazosin plus propranolol or by guanethidine, implying that ATP is released from non-neuronal origin. In contrast, in papillary muscle segments, the test cardiotonics did not elicit any ATP release despite producing contractile response similar to that in atrial preparations. However, there is no difference in ectoATPase activities of both tissues. Adenosine added exogenously inhibited electrically evoked-contraction of the atrium, but not that of the papillary, although inhibitions by verapamil of the contractions were approximately equal in these preparations. These findings suggest that cardiotonics such as isoproterenol produce a liberation of ATP from auricle muscles, but not from ventricle muscles, and that the liberated ATP may mainly be catabolized to adenosine by ectoenzymes and the resultant nucleoside may serve as a functional modulator through stimulation of pre or postsynaptic A1 receptors. PMID- 8366764 TI - Suppression of plasma endothelin-1 level by alpha-human atrial natriuretic peptide and angiotensin converting enzyme inhibition in normal men. AB - The effect of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) on plasma endothelin-1 (ET-1) level was examined in 6 healthy subjects. Intravenous infusion of alpha-ANP (0.1 micrograms/kg/min) resulted in significant falls in plasma renin activity and aldosterone, but without effect on ET-1 level. An angiotensin converting enzyme inhibitor, captopril, increased plasma renin activity and decreased aldosterone, respectively. However, plasma ET-1 levels were not modified by captopril. In cases with alpha-hANP infusion after captopril (25 mg, p.o.,), the renin-angiotensin-aldosterone system was further inhibited compared with the first group, and ET-1 at 60 min was significantly suppressed from the baseline. These data suggest that alpha-hANP when combined with captopril brings about the suppression of plasma ET-1 concentrations in men. PMID- 8366765 TI - Inhibitory action of azelastine on cytokine production from human peripheral blood leukocytes in vitro. AB - Effects of azelastine (AZ) on human peripheral blood leukocytes (PBL) in culture were examined. Addition of 10.0 micrograms/ml of AZ resulted in a marked inhibition of PBL blastic activity, but lower concentrations (1.0 and 0.5 microgram/ml) had no demonstrable suppressive effects on the activation. Interleukin (IL)-2, IL-3 and IL-4 production from PBL in response to Concanavalin A stimulation was also strongly suppressed when the cells were cultured in the presence of AZ. This suppression was observed even when lower concentrations (1.0 and 0.5 microgram/ml) of AZ were added to cell cultures. PMID- 8366766 TI - Study on the suppressive effect of iodine-enriched egg on LT-C4 production in arachidonic acid-induced ear inflammation. AB - The anti-inflammatory mechanism of iodine-enriched egg was investigated in mice by means of arachidonic acid-induced ear inflammation. The lipid fraction of iodine-enriched egg was capable of suppressing the increase in ear weight induced by arachidonic acid in a dose-dependent manner. The lipid fraction was further separated into neutral and polar lipid fractions. Of these two fractions, only the neutral lipid fraction was capable of suppressing LT-C4 production in arachidonic acid inflammation. Neither the neutral nor polar lipid fractions of ordinary egg, however, showed any anti-inflammatory effect. These results suggest that the anti-inflammatory activity of iodine-enriched egg is present in the neutral lipid fraction, and its mechanism is assumed to be inhibition of LT-C4 production. PMID- 8366767 TI - Morin hydrate is a plant-derived and antioxidant-based hepatoprotector. AB - Morin hydrate, or simply morin, is shown here to be an effective hepatoprotector in vitro and in vivo. Between 0.25-2.0 mM, morin prolongs survival of rat hepatocytes against free radical damage triggered by xanthine oxidase hypoxanthine, and substantially better than equimolar concentrations of Trolox (a vitamin E analogue), mannitol, and ascorbate. In a rat model of 80 min ischemia 24 h reperfusion in the liver, infusion of morin at 2.5, 5.0 and 10 mumol/Kg body weight before reperfusion reduces liver necrosis in the placebo control by 51.48 +/- 9.94%, 66.55 +/- 2.18%, and 79.37 +/- 11.03%, respectively, for n = 6 per group. Mechanistically, morin acts in a two-pronged manner: as a preventive antioxidant by partially inhibiting xanthine oxidase and partly as a curative antioxidant by scavenging oxyradicals. The role of morin as an effective free radical scavenger is further evidenced by its ability to protect human red cell membrane from peroxidative attack better than ascorbate, Trolox, and mannitol. Collectively, our data demonstrate that morin is an effective hepatoprotector, both in cultured cells and in hepatic ischemia-reperfusion. PMID- 8366768 TI - Lipid fluidity modulates platelet aggregation and agglutination in vitro. AB - To determine the effect of altered membrane fluidity on platelet aggregation/agglutination, fresh, washed human platelets were treated with A2C, a cyclopropyl fatty acid ester which is known to enhance mobility of intrinsic membrane bilayer constituents and increase membrane fluidity. Fluorescence polarization studies demonstrated A2C incubation time- and concentration dependent increases in platelet membrane fluidity (decreased fluorescence anisotropy). Preincubation with A2C was associated with diminished collagen, thrombin and ristocetin-induced platelet aggregation/agglutination. Aggregation/agglutination was diminished by 93 +/- 5% for collagen (0.2 mg/ml), 53 +/- 3% for thrombin (1.0 U/ml) and 85 +/- 9% for ristocetin (1.1 mg/ml). These data suggest that membrane fluidity is involved in the regulation of platelet function. PMID- 8366769 TI - Activin A: its effects on rat pancreatic islets and the mechanism of action involved. AB - Activin A now used as a recombinant product was first isolated from ovarian fluid. Its effects on insulin and glucagon secretion, 45Ca2+ net uptake, 86Rb+ efflux and inositol-trisphosphate (Ins-1,4,5-P3) content were investigated in rat pancreatic islets. Activin A increased insulin secretion at either 3.0, 8.3 or 16.7 mM glucose. It decreased glucagon secretion at 3.0, had no effect at 8.3 and increased glucagon secretion at 16.7 mM glucose. The effect on insulin release was concentration dependent; effects were obvious at 1 and 10 nM activin A. The effect on insulin release was paralleled by an effect on 45Ca2+ net uptake. 10 nM activin A were effective in elevating Ins-1,4,5-P3 content at either glucose concentration used. 86Rb+ efflux as an indicator for closing K+ channels which leads to a depolarization of the beta-cell membrane and which is a prerequisite for Ca++ influx was inhibited by activin A at a low glucose concentration (3.0 mM). The data indicate that the new peptide activin A elevates insulin release at various glucose concentrations: at low and high glucose concentrations 45Ca2+ uptake is involved. At low glucose concentrations inhibition of 86Rb+ efflux is a prerequisite sufficient to lead to a depolarization and subsequent Ca++ uptake; accumulation of Ins-1,4,5-P3 probably helps mediating the insulinotropic effect by additionally elevating intracellular Ca++. PMID- 8366770 TI - Melatonin effect on serotonin uptake and release in rat platelets: diurnal variation in responsiveness. AB - The present study was conducted to examine whether melatonin impairs serotonin (5HT) release and uptake in rat platelets. Exposure of platelet-rich plasma samples (PRP) to melatonin induced a concentration-dependent inhibition of 5HT uptake and the value of IC50 was 1.3 x 10(-3) M. We have also investigated the melatonin effect on the kinetic parameters of platelet 5HT uptake. Transport capacity was inhibited (Vmax; CONTROL: 2.28 +/- 0.52, Melatonin: 0.74 +/- 0.13 pmol/10(7) platelet.min; p < 0.05) while the affinity of 5HT for its uptake carriers remained unaltered, thus indicating a non-competitive effect. Studies carried out to determine the existence of a differential morning (8:00h)-evening (21:00h) melatonin effect showed a higher platelet uptake sensitivity at 8:00h (two-way ANOVA, p < 0.001). Spontaneous 5HT release was not impared by the hormone and no daily variation in sensitivity was detected. The possible mechanism of action of melatonin on platelet transport is discussed, and the results support the suitability of the platelet model for studying sensitivity changes in target cells to the hormone. PMID- 8366771 TI - Uptake of docosahexaenoic acid by microvessels from developing rat brain. AB - Uptake of polyunsaturated fatty acids by the rat brain occurs mainly during the three weeks before weaning. Docosahexaenoic acid [22:6], the predominant polyunsaturated fatty acid in the adult brain, appears to be preferentially taken up from the circulation by both the adult and developing rat brain. To test the hypothesis that this preferential incorporation was mediated by the cerebral microvasculature, we compared the incorporation of 22:6 to a saturated fatty acid, palmitic acid [16:0], in freshly isolated rat brain microvessels from the pooled brains of entire litters of two-week-old rats (n = 8 litters). For each litter duplicate incubations with 2 microCi of [1-14C]22:6 or [1-14C]16:0 were performed in 60% autologous rat serum for 2 hr at 37 degrees C. [3H]Sucrose was included in each incubation, allowing correction for non-specific uptake and trapping. An average of 2.7 +/- 2.0% (SD) of the radioactivity from 16:0 was found in the microvessels after 2 hr, vs 0.9 +/- 0.6% for 22:6. This yielded a three-fold enrichment of 16:0 over 22:6 (P = 0.02, paired t-test). There was preferential incorporation of 22:6 into phosphatidylethanolamine and of 16:0 into phosphatidylcholine, although most of the label from either substrate remained as fatty acid after the 2 hr incubation. These results do not indicate that brain capillaries mediate the preferential incorporation of polyunsaturated fatty acids into brain tissue that was seen in intact young rats. PMID- 8366772 TI - Reduced incidence of stress ulcer in germ-free Sprague Dawley rats. AB - Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model. PMID- 8366773 TI - Interactive dietary interviewing for patients? PMID- 8366774 TI - Telematics in health care: trends in the European community. PMID- 8366775 TI - An interactive dietary interview for hospital employees. PMID- 8366776 TI - The tenth annual directory of medical hardware and software companies. PMID- 8366777 TI - ShrinkRapt: a database manager for the Macintosh. AB - The bad news about ShrinkRapt is that its clinical potential remains, mostly, potential. The good news is that ShrinkRapt works. It concentrates on the fundamentals, stimulates thinking, and appears to be backed up by a creative and dedicated company. It is versatile enough to fit many practice styles and volumes of record keeping. A solo practitioner with a part-time psychotherapy practice and a Macintosh in the office can enter data at the end of the day or the end of a session, typing up patients' progress notes while they are still fresh in memory and keeping abreast of session data and documentation requirements. At the end of the month, a few keystrokes generate bills and claims forms. PMID- 8366778 TI - Fluoridation: a lawyer looks at the issues. PMID- 8366779 TI - Police may underuse Section 136. AB - A one-year prospective study comparing Section 136 patients (39) and the severe Section 2 or 4 patients (29) of the Mental Health Act 1983 in a hospital with inner London catchment areas. The assessments were clinical, nurses' ratings and socio-demographic. The results showed that clinical and nursing ratings did not differentiate the two groups. Most social/demographic data showed similar trends with both groups being disadvantaged but Section 136 patients slightly more so. The differences were smaller than anticipated, suggesting a recent shift of patients admitted under Section 2 or 4 towards a more socially disadvantaged position. In conclusion, police did not overuse Section 136. Our comparison suggests: (a) police may underuse Section 136, and (b) Section 136 acts as a valuable 'back-up' for those patients who would otherwise fail to benefit from the Mental Health Act. PMID- 8366780 TI - Viewing human remains following disaster: helpful or harmful? AB - Seventy-four bereaved of the Zeebrugge Disaster completed symptom measures some 30 months following the tragedy. The group was divided into those who viewed or did not view the body and according to time of recovery, i.e. the first night, the following weeks, at the time of righting of the ship, and subsequently. For the two main groups, where body recovery was made on the first night or on the righting of the ship, intrusive and avoidant symptomatology were lower in those who viewed, but general psychological symptoms and measures of bereavement were not affected. The implications of the findings are discussed in relation to post disaster management. PMID- 8366781 TI - Medical examination of children thought to have been sexually abused. PMID- 8366782 TI - Sex offenders--cure or management? AB - A variety of biological, psychoanalytical and behavioural treatment strategies have been employed to treat sex offenders. Whilst these may produce short-term benefits, their efficacy in reducing long-term recidivism is uncertain. It is possible that treatment, as generally understood, is too ambitious an aim for this group of people and better results could be expected by employing a management strategy that includes treatment as well as life-long vigilant supervision. This can only be achieved if psychiatric services, which are used in continuing care, get involved in the management of sex offenders. PMID- 8366783 TI - Cellular changes and time since death. AB - Based on a hypothesis that post-mortem cellular (chiefly nuclear) changes in the white blood cells could reliably be correlated with the time interval since death, (ti), serial observations were made on the counts (total, differential) and light-microscopically observable 'degenerations' of white blood cells obtained from 30 non-refrigerated cadavers (experimental group) and similar cells obtained from 200 hospital patients (control group). While neutrophils degenerated rapidly, lymphocytes did so slowly; the eosinophils and monocytes degenerated at rates between these extremes. In cadaveric blood total counts of identifiable leucocytes on average dropped to zero by 84 hours, identifiable eosinophils and monocytes were first to 'disappear' (by 60 hours), followed by neutrophils (by 66 hours), and finally lymphocytes: identifiable lymphocytes disappeared completely at or around 84 hours from the time of death. This 'differential degeneration' was surprising but useful. Based on the use of all four characteristics--total and differential white cell counts, differential degeneration and morphology of cells--a method for a reasonably exact estimation of ti is presented. The method is appropriate for ti up to 84 hrs (3 1/2 days). Zero white cell counts (total, differential) and bizarre morphology (unidentifiable white blood cells) indicate a ti > 84 hrs. Avenues for further research are indicated. PMID- 8366784 TI - Eating disorders and shoplifting--a study in two settings. AB - Two groups of female shoplifters drawn from a specialist out-patient service (52) and a Magistrates' Court (50) are compared for their level of eating disorder. Only one person knew of a previous diagnosis of eating disorder. Their levels of eating disorder and general psychopathology are high in both settings but particularly those referred for psychiatric assessment. Those with an eating disorder had significantly higher levels of psychiatric disturbance, depressive illness and hoarding behaviour. PMID- 8366786 TI - Mild head injury is not always mild; implications for damage litigation. AB - The traditional view that mild head injury involves an essentially reversible physiological process is examined and is found to be largely invalid. It is concluded that long-term impairment following mild head injury is fairly common and that the degree of impairment can be assessed clinically. Such an assessment involves a combination of objective electrophysiological and psychometric investigations as well as professional interpretation. With the use of this approach the possibility of malingering can be ruled out in most cases and significant impairment, when it exists, can be demonstrated beyond reasonable doubt. PMID- 8366785 TI - An increase in violence among psychiatric inpatients: real or apparent? AB - Levels of violence amongst psychiatric in-patients appear to be increasing. Possible reasons for this are explored and include methodological differences between studies, increased staff awareness and perception of violence, changes in staff attitude, changes in psychiatric practice in recent years, staffing levels and increased violence in society generally. PMID- 8366787 TI - Paralytic shellfish poisoning in Chile. PMID- 8366788 TI - Season, climate and suicide in Singapore. AB - In Singapore, an island city state in the tropics, climatic variables like sunlight, windspeed, temperature, rainfall and humidity are significantly correlated with subgroups of suicidal subjects such as Malays, young adults and youths. In the young age group (0-19 years) the relationship between meteorological factors and suicide appear to be greater than in the other two groups. PMID- 8366789 TI - Glue sniffing deaths in Singapore--volatile aromatic hydrocarbons in post-mortem blood by headspace gas chromatography. AB - Over a period from 1983 to 1991, of a total of 19,000 post-mortems, 33 were found to have at least one aromatic hydrocarbon (benzene, toluene or xylenes) in the blood. Of the 33 deceased, 22 had a history of toluene or petrol abuse while most of the remaining 11 were suspected to be glue sniffers through evidence found at the scene. This number, which represented 0.17 per cent of all the unnatural deaths, is considered small for a nation having a glue sniffing epidemic. The low death rate, as compared to 2.1 per cent through drug and chemical poisoning during the same period, is attributed to the timely intervention by the Government who outlawed glue sniffing and the effectiveness of compulsory rehabilitation. The male gender predominates (81.8 per cent) among the 33 deceased with a mean age of 20.1 years (range 15 to 33). The mean age for the female gender is 17.7 years (range 16 to 20). The blood toluene levels were found to be in the range 0.2 to 92 micrograms per ml blood. The causes of death are: 63.6 per cent due to falling or suicide by jumping; 18.2 per cent drowning; 6.1 per cent hanging; 6.1 per cent homicide; and 6.1 per cent acute toluene poisoning. The high proportion of traumatic deaths are discussed. Headspace gas chromatography with a suitable GC column was used for the analysis. Calibration blood standards were prepared in situ or in bulk stabilized by 10 per cent (v/v) methanol to overcome the hydrophobic and volatile nature of the aromatic hydrocarbons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366790 TI - Impaling-type head injury in a road traffic incident. AB - A fatal impaling-type head injury is described in a young man, sustained when he crashed his car while intoxicated, his head being transfixed by a broken wooden fence post. This shattered the facial bones and damaged the brain stem. Other published instances of impaling head injuries are discussed. PMID- 8366791 TI - Failure of a feeding jejunostomy. AB - A healthy 16-year-old female pedestrian was hit by a motor vehicle. She sustained multiple injuries including severe head injury. She was admitted to hospital unconscious. There was no recovery of neurological function. After a short period of time, a jejunostomy was performed for feeding purposes. The major clinical problem continued to be a feeding difficulty, with profuse diarrhoea occurring. At no stage was it possible to adequately nourish her. Hyperperistalsis was noted whilst in hospital. She died just over three months after admission. Autopsy revealed an emaciated body weighing only 25kg. An upper jejunostomy was still present containing a No. 20 French catheter. The bulb had threaded down the small bowel so that it was situated 25cm proximal to the ileocaecal valve. The small bowel was empty. The cause of death was given as malnutrition due to failure of function of a feeding jejunostomy due to small bowel hyperperistalsis in an individual with diffuse brain trauma. This complication of feeding jejunostomy causing death from malnutrition has not previously been described in the English literature. PMID- 8366793 TI - Forensic examinations in two cases of alleged dowry deaths. AB - Two cases of alleged dowry deaths are presented from Haryana State, India. In each case a young lady died after receiving burn injuries. Forensic examination unveiled the mysteries of both deaths and helped in apprehending and prosecuting the culprits. Case 1, allegedly a dowry death, proved to be an accidental burning and Case 2, stated to be a suicidal death, was proved to be homicidal. PMID- 8366792 TI - Ring fracture of the base of the skull and atlanto-occipital avulsion due to anteroflexion on motorcycle riders in a head-on collision accident. AB - This report concerns a head-on collision accident of a motorcycle at a very high speed (c. 80-100 Km/h) against a bonnet-type automobile, in which both the motorcyclist and pillion rider were injured at the base of the skull by violent anteroflexion of the head due to the force of inertia. A difference in their injuries was: the motorcyclist sustained a 'ring' fracture and the pillion rider an atlanto-occipital avulsion; dural tear. Anteroflexion without impact on the occiput such as described above seems to be a rare causal mechanism of the 'ring' fracture. In addition, the mode of action of the accelerating forces to the heads of the victims along with their physiques may explain the mechanism which caused the different injuries in this accident. PMID- 8366794 TI - The fatal paracetamol dosage--how low can you go? PMID- 8366795 TI - In vivo localized proton NMR spectroscopy of silicone. AB - 1H NMR localized spectroscopy (STEAM) can assess unambiguously the presence of free chemically unchanged silicone in animal tissue after injection of silicone oil. Although the signal-to-noise ratio obtained in 1H imaging is sufficient to detect the distribution of relatively large amounts of silicone in vivo, the specificity of silicone detection can be improved by using 1H localized spectroscopy techniques. The sensitivity of the STEAM experiments is sufficient to detect silicone at a concentration of 0.5% in a voxel of 27 mm3. Preliminary results from rats with silicone gel-filled implants show no detectable amounts of silicone in sites such as lymph nodes, the liver or the spleen, 3 or 6 months after implantation. PMID- 8366796 TI - In vivo proton spectroscopy of meningioma after preoperative embolization. AB - The time course of proton spectra of meningioma after embolization has been followed using a localized PRESS experiment with 135 ms of echo time. The most conspicuous findings were the observation of transient lactate signal within 24 h after blocking of the capillary bed. After that time large aliphatic signals from necrosis were observed, whereas other metabolite signals vanished. It was demonstrated, that tumor necrosis as shown by proton spectroscopy is complete within 4 days. This finding is significant for the timing of surgery, which can be performed after this period. PMID- 8366797 TI - Processing strategies for time-course data sets in functional MRI of the human brain. AB - Image processing strategies for functional magnetic resonance imaging (FMRI) data sets acquired using a gradient-recalled echo-planar imaging sequence are considered. The analysis is carried out using the mathematics of vector spaces. Data sets consisting of N sequential images of the same slice of brain tissue are analyzed in the time-domain and also, after Fourier transformation, in the frequency domain. A technique for thresholding is introduced that uses the shape of the response in a pixel compared with the shape of a reference waveform as the decision criterion. A method is presented to eliminate drifts in data that arise from subject movement. The methods are applied to experimental FMRI data from the motor-cortex and compared with more conventional image-subtraction methods. Several finger motion paradigms are considered in the context of the various image processing strategies. The most effective method for image processing involves thresholding by shape as characterized by the correlation coefficient of the data with respect to a reference waveform followed by formation of a cross correlation image. Emphasis is placed not only on image formation, but also on the use of signal processing techniques to characterize the temporal response of the brain to the paradigm. PMID- 8366798 TI - MRI and MRS studies on the time course of rat brain lesions and the effect of drug treatment: volume quantification and characterization of tissue heterogeneity by parameter selection. AB - Magnetic resonance imaging has been used to follow the time course of lesions induced in the rat brain as an animal model for characterization of the volume of the lesion. The dispersion in spin-spin relaxation has been used to characterize the nature of the brain lesion. Parameter selective estimation of T2, quantitative determination of the lesion size and volume selective in vivo proton spectroscopy have been employed for the purpose. The work has been carried out on rats which were subject to lesioning by ibotenic acid as a model for excitotoxicity and also on rats which received doses of ibotenic acid and subsequent doses of the NMDA antagonist drug MK 801 (dizocilpine). The time course of the progress of the lesions in untreated animals and the effect of neuroprotection by MK 801 was continuously monitored in all test animals. Further, a relatively new inhalation anesthetic agent, isoflurane, has been employed. A more logical and semiquantitative T2 bandwidth demarkation useful in distinguishing different degrees of lesioning from the onset and up to the 'edema' stage through penumbra (mild lesion), medium degree lesion and severe lesion has been proposed. PMID- 8366799 TI - Stabilization of echo amplitudes in FSE sequences. AB - The classical CPMG sequence and its extension as an imaging sequence, fast spin echo (FSE, based on RARE), suffer from signal magnitude variations in the early echoes when the refocusing pulses are not set exactly to 180 degrees. It has been suggested that by varying the value of the nutation angle of each refocusing pulse the signal magnitude could be made constant. This article describes an algorithm permitting the generation of sequences of nutation angles yielding series of echoes with constant signal magnitudes. This result is then used to design selective pulses for the FSE imaging technique. PMID- 8366800 TI - Improved myocardial tagging contrast. AB - Myocardial tagging is a new noninvasive MRI method that allows the study of myocardial motion with high accuracy. However, with conventional tagging techniques tagging contrast is impaired at later heart phases due to longitudinal relaxation. An improved method, called Complementary SPAtial Modulation of Magnetization (CSPAMM), which separates the component of the magnetization with the tagging information from the relaxed component by subtraction of two measurements with first a positive and then a negative tagging grid, is presented. This technique improves the grid contrast and greatly facilitates the automatic evaluation of the myocardial motion. Thus the motion assessment of the entire heart cycle becomes possible. The improvements are documented by numerical simulations and by experiments on phantoms and on human volunteers. PMID- 8366801 TI - Diffusion-weighted MR microscopy with fast spin-echo. AB - A diffusion-weighted fast spin-echo (FSE) imaging sequence for high-field MR microscopy was developed and experimentally validated in a phantom and in a live rat. Pulsed diffusion gradients were executed before and after the initial 180 degrees pulse in the FSE pulse train. This produced diffusion-related reductions in image signal intensity corresponding to gradient ("b") factors between 1.80 and 1352 s/mm2. The degree of diffusion weighting was demonstrated to be independent of echo train length for experiments using trains up to 16 echoes long. Quantitative measurements on a phantom and on a live rat produced diffusion coefficients consistent with literature values. Importantly, the eight- to 16 fold increase in imaging efficiency with FSE was not accompanied by a significant loss of spatial resolution or contrast. This permits acquisition of in vivo three dimensional data in time periods that are appropriate for evolving biological processes. The combination of accurate diffusion weighting and high spatial resolution provided by FSE makes the technique particularly useful for MR microscopy. PMID- 8366802 TI - Spatially resolved and localized real-time velocity distribution. AB - A technique is presented for collecting the spin velocity distribution as a function of position and time. It uses a multidimensional excitation pulse to select a cylinder, giving localization in two dimensions. Resolution in the third spatial dimension is achieved in the readout. During readout, an oscillating gradient encodes the acquired data in both one spatial dimension (x) and one velocity dimension (v). Two acquisitions (42 ms each) are needed to get a complete coverage of kx--kv space, which makes this technique real-time. The data is interpolated from the nonuniformly sampled kx--kv space to a Cartesian frame with a gridding scheme to take advantage of the Fast Fourier Transform. The technique was successfully applied to phantoms and normal volunteers, giving reasonable real-time measurements of velocity. PMID- 8366803 TI - Novel approaches to low-cost MRI. AB - This paper presents a combination of speculative approaches, some related to earlier work and some apparently novel, which show great promise in providing a new class of MRI machines that would be considerably less expensive. This class would have advantages and disadvantages as compared to existing MRI, over and above that of low cost. The disadvantages include the apparent inability to perform classic spectroscopy, and limited flexibility in the area of selective excitation. The advantages include a fundamental immunity to inhomogeneity and susceptibility problems, the ability to create a wide class of machines that are designed for specific anatomy-related applications, the ability to design open machines for physician access, and improved capability for high speed imaging. Generic to all of the methods presented are a pulsed polarizing field and an oscillatory read-out bias field. The pulsed field initially polarizes the magnetic moments. Since it is not on during the readout operation it has negligible homogeneity requirements since changes in the field amplitude will merely shade the image intensity. During readout a relatively low bias field is used. To enable the use of a relatively inhomogeneous bias field, an oscillatory field is used that has a zero average value. This prevents any long-term buildup of phase errors due to a frequency error associated with inhomogeneity. Thus the average bias frequency will be determined solely by the frequency rather than the amplitude of the bias field. Three methods are described, all including the above features. The first two involve imaging in the laboratory frame, while the third involves imaging in the rotating frame. The second approach requires no RF excitation and the third approach uses RF bias and gradient signals. Some approaches to slice selection are described. PMID- 8366804 TI - 13C NMR investigation of synovial fluids. AB - 13C NMR spectra of synovial fluids from 20 patients suffering from rheumatic diseases have been recorded. Structural changes in hyaluronic acid, the main carrier of the viscoelastic properties of synovial fluid, could be observed in the NMR spectra of the native biological fluid. By comparing these spectra with those of purified hyaluronic acid, a rough estimation of the degree of depolymerization of synovial hyaluronic acid was possible. The patients with rheumatoid arthritis appeared to have a lower degree of polymerization compared to patients with osteoarthrosis. Thus, 13C NMR spectroscopy provides useful information about biophysical properties of synovial fluid. PMID- 8366805 TI - Changes in water diffusion and relaxation properties of rat cerebrum during status epilepticus. AB - Diffusion-weighted (DW) imaging has been used to record changes associated with status epilepticus (SE) in rat brain. It was found that the apparent diffusion coefficient (ADC) of water in brain decreased 14-18% during SE, and it fell a further 20-22% when the animals were sacrificed. The transverse decay time constant T2* showed corresponding reductions, but no significant changes were seen in relaxation times T1 or T2 values. Changes in ADC in status epilepticus are similar to those seen in stroke and ischemia but occur under very different conditions of blood flow and metabolism. PMID- 8366806 TI - Magnetic resonance microscopy in rat skeletal research. AB - Noninvasive evaluation of skeletal tissue, particularly certain sites that tend to be predisposed to disease, is critical in understanding the pathogenesis, progression, and successful treatment of various diseases like osteoporosis, rheumatoid arthritis, and osteoarthritis. Although several noninvasive techniques are currently available to evaluate skeletal tissues, they all have critical limitations. We report here a systematic study to compare the morphological changes (overall profile and tissue architecture) in the proximal tibiae and coccygeal vertebrae of a young growing rat and an older retired female breeder rat using 2- and 3-dimensional MR (magnetic resonance) microscopy and histology. We have obtained MR microimages of intact rat tibiae and vertebrae with resolution upto 24 24 250 microns and have found excellent correlations between MR microscopy results and histological assessment. PMID- 8366807 TI - Fast MRI by creating multiple spin echoes in a CPMG sequence. AB - A fast multislice imaging technique has been developed. RASTER (Rapid Acquisition with STimulated Echo Refocusing) is based on RARE (Rapid Acquisition with Relaxation Enhancement), and creates multiple spin echoes/each 180 degrees pulse utilizing stimulated echoes, and phase encode each differently. The sequence can be much faster than RARE while keeping the same spin echo image contrast. The main limitation of the technique is reduced signal-to-noise ratio. PMID- 8366808 TI - Self-correction of proton spectroscopic images for gradient eddy current distortions and static field inhomogeneities. AB - A postprocessing method of correcting for gradient eddy current distortions and inter-voxel static field inhomogeneity in spectroscopic imaging is presented. Data is acquired normally and all spatial processing is performed. The FID in each voxel is then digitally filtered to extract the signal from a single reference line. Phase multiplying the original FID by the phase of this reference signal corrects for gradient eddy currents and static field offsets. Computer simulations show that the method is robust with respect to noise, filter bandwidth and the presence of small lines close to the reference line. The method is demonstrated on proton spectroscopic images of phantoms. PMID- 8366810 TI - MRI evaluation of myocardial perfusion without a contrast agent using magnetization transfer. AB - We propose a new magnetic resonance imaging (MRI) technique that is sensitive to myocardial tissue perfusion that obviates the use of an extrinsic contrast agent. Significant advantages of such a technique are that it avoids accumulation of contrast agent when repeated studies are performed on the same subject and that it is completely noninvasive. The method makes use of a combination of magnetization transfer (MT) and T1sat (measured spin-lattice relaxation time in the presence of MT) weighting. In this Communication, we present observations from experiments with an isolated rat heart model that demonstrate increase of MT weighted signal intensity and T1sat with flow. Also included are data showing that these effects can be made synergistic for enhancing the sensitivity to perfusion. We have observed about a 3% change in MT-weighted intensity and up to 10% change in MTT1sat-weighted intensity for a change of 1 ml/min in global flow rate. PMID- 8366809 TI - Transaminase reaction rates, transport activities and TCA cycle analysis by post steady state 13C NMR. AB - In this work, we present the post-steady state analysis of the TCA cycle and a closed form solution to the rate of label washout from the C4 carbon of glutamic acid through the transaminases and the malate-aspartate shuttle and then through alpha-ketoglutarate dehydrogenase. We demonstrate using a model of this problem that the rate of label washout depends not only on the flux through alpha ketoglutarate dehydrogenase, but most importantly on the activity of the malate aspartate shuttle as determined by the forward and reverse fluxes through the transaminases and by the rate of transport of glutamate and alpha-ketoglutarate across the mitochondrial membrane. PMID- 8366811 TI - Magnetization-prepared cardiac imaging using gradient echo acquisition. AB - Magnetization-prepared 2DFT and 3DFT gradient echo techniques are presented for acquisition of black blood cardiac images. Both methods incorporate RF pulses for blood saturation, centric or centric-like view ordering, data acquisition during late diastole, and breath-holding. In a series of 13 volunteer studies, these methods have consistently provided good visualization of intraventricular structures. PMID- 8366812 TI - Ivermectin and human lymphatic filariasis. PMID- 8366813 TI - The cellular immunology of bovine paratuberculosis: immunity may be regulated by CD4+ helper and CD8+ immunoregulatory T lymphocytes which down-regulate gamma/delta+ T-cell cytotoxicity. AB - In a previous investigation, we obtained evidence that the major histocompatibility complex (MHC)-restricted proliferative response of CD4+ lymphocytes to Mycobacterium paratuberculosis antigens was depressed in naturally infected and immunized animals. Findings suggested that depression of the response was attributable to an abrogation in the ability of CD4+ cells to respond to specific antigens and/or the actual loss of antigen-reactive cells. In vitro cell experiments indicated that the depression was associated with the presence of gamma/delta+ T cells that modulated CD4+ cell function. Examination of additional animals confirmed and extended these observations and showed that the ability of gamma/delta+ T cells to regulate CD4+ responses were blocked by the presence of CD8+ cells. CD4+ T cells from some exposed animals incorporated [3H]-thymidine in the presence of CD8+, gamma/delta+ cells and/or antigen and antigen-presenting cells, but CD4+ cell proliferation was abrogated when CD8+ were excluded from the assays. Likewise, gamma/delta+ T-cell proliferation was abrogated when CD8+ cells were present. The mechanism by which CD8+ cells blocked gamma/delta+ T-cell responses could not be determined, however, the observed effect resembled the veto cell phenomenon. The data suggest that the development of protective immunity against M. paratuberculosis may be dependent on the capacity of CD8+ cells to modulate the regulatory activity of gamma/delta+ T populations. PMID- 8366814 TI - Delayed (footpad) hypersensitivity and Arthus reactivity using protein-rich antigens and LPS in mice immunized with live attenuated aroA Salmonella vaccines. AB - Footpad reactions to protein-rich salmonella extracts and lipopolysaccharide (LPS) were studied in BALB/c mice 2 and 8 months after immunization with the Salmonella typhimurium SL3261 aroA live vaccine. T-cell depletion in vivo and adoptive serum transfer showed that protein-rich antigens induced T-cell dependent delayed hypersensitivity reactions, whereas LPS only elicited Arthus reactions. The footpad reactions to crude protein extracts were not always T-cell mediated, but depended on the nature and the dose of the antigen. Selective depletion of CD4+ T cells alone had a greater effect than depletion of CD8+ T cells alone, but neither was as marked as simultaneous depletion of both CD4+ and CD8+ T cells, which abolished the delayed type hypersensitivity (DTH) response. Crude protein-rich extracts subjected to alkaline hydrolysis (which removes some ester-linked fatty acids and causes disaggregation of LPS resulting in decreased toxicity while conserving O-specificity) still gave positive T-cell dependent reactions, but with reduced T-cell independent reactivity. Purified phenol-water LPS (2.5 micrograms) produced Arthus reactivity which could be confused with DTH. LPS induced positive reactions which still occurred in T-cell depleted mice and were transferable by immune serum. Arthus reactions did not occur when using alkali-treated LPS, which showed reduced complement fixation in vitro when using serum from immunized mice. The results indicate that footpad testing using salmonella antigens containing LPS elicit DTH but can also produce toxic reactions, some of which are T-cell independent and not necessarily a true measure of DTH. Arthus reactivity to LPS can be confused with DTH. Alkaline hydrolysis of the antigens can eliminate non-specific reactogenicity while retaining the ability of the (protein-rich) antigen to elicit a true T-cell dependent footpad response, which requires the participation of both CD4+ and CD8+ T cells. PMID- 8366815 TI - Non-toxigenic derivatives of the Ames strain of Bacillus anthracis are fully virulent for mice: role of plasmid pX02 and chromosome in strain-dependent virulence. AB - The toxin-encoding plasmid pX01 and capsule-associated plasmid pX02 are required for full virulence of Bacillus anthracis in some animals. However, the non toxigenic pX01-cured derivatives of certain anthrax strains are not completely attenuated for mice, and their virulence is strain-dependent. The strain-related differences were partially associated with plasmid pX02 as demonstrated by pX02 transductants of the attenuated vaccine strain UM23-1 cured of pX01. To determine the virulence of non-toxigenic variants of virulent strains, we isolated pX01- derivatives of the Vollum 1B strain and the more 'vaccine-resistant' Ames strain which carried pX02 from either Ames or Vollum 1B. The 50% lethal dose (LD50) values of the derivatives of both strains which carried the Ames pX02 were not significantly different from the LD50s of the pX01+ pX02+ strains (and were lower than those of pX01+ pX02- strains). pX02+ derivatives of strain UM23-1 were less virulent than the comparable Ames and Vollum 1B strain derivatives, emphasizing a role for chromosomal loci in the virulence of the latter two strains. Non toxigenic isolates which carried the Ames pX02 were more virulent for CBA/J mice than those with Vollum 1B pX02, and the differences were mouse strain-dependent. The pX01- pX02+ strains multiplied and achieved high concentrations systemically. PMID- 8366816 TI - The interaction of primate transferrins with receptors on bacteria pathogenic to humans. AB - The binding of primate transferrins by receptors in the human pathogens Neisseria meningitidis, Moraxella (Branhamella) catarrhalis, and Haemophilus influenzae was assessed and compared with the binding of anti-human transferrin monoclonal antibodies by primate transferrins. In competitive binding assays the three pathogens showed identical specificity for primate transferrins. Only human, gorilla, chimpanzee and orangutan sera were capable of blocking binding of labelled human transferrin. Direct binding assays and affinity isolation of receptor proteins confirmed that chimpanzee transferrin, but not rhesus monkey transferrin, was capable of effectively binding to the bacterial receptors. Five distinct patterns of binding were seen when five anti-human transferrin monoclonal antibodies were reacted with the primate transferrins and these patterns reflected phylogenetic relatedness of these species to humans. A monoclonal antibody which showed transferrin-binding specificity identical to that seen with the bacterial receptors was found to block binding of human transferrin by receptors in the three bacterial species. PMID- 8366817 TI - Clonal relationships and variation in virulence among Escherichia coli strains of avian origin. AB - Average genetic relatedness among 44 Escherichia coli strains of serotypes O1, O2, and O78 isolated mainly from birds with colibacillosis or swollen-head syndrome from France or Saudi Arabia was estimated based on allelic variation detected by multilocus enzyme electrophoresis. For 20 enzyme-encoding loci, we resolved 2.8 alleles per locus and distinguished 17 electrophoretic types (ETs) that were used to mark naturally occurring cell lineages or clones. On average, ETs differed at 37% of their loci. Forty-eight percent of the isolates represent three ETs, two of which belong to previously defined complexes of clones identified in avian disease in North America and Europe. Virulence of strains, assessed in experimental infections of day-old chicks, showed little variation among isolates of a clone, but was significantly variable among isolates of different clone complexes. These findings add support to the evidence that a majority of avian isolates that cause colibacillosis belong to a few cosmopolitan pathogenic clones and indicate a substantial between-clone component of pathogenicity. PMID- 8366818 TI - Effects of the acetylcholinesterase toxin of Aeromonas hydrophila on the central nervous system of fish. AB - The purified acetylcholinesterase (AcChE) toxin, crude extracellular products (ECP) or viable virulent Aeromonas hydrophila were injected intraperitoneally into rainbow trout in different sublethal and lethal doses. When fish showed signs of morbidity, brain tissue was excised and assayed for acetylcholinesterase activity. In all cases there was a large increase in AcChE activity (about 40 fold for purified AcChE-toxin). This was shown to be due to an accumulation of the fish's own AcChE and not the bacterial toxin. Nevertheless, the latter was detected in brain homogenates from fish in all treatment groups using a rabbit antiserum to the purified toxin to probe Western blots of brain homogenates, demonstrating that the toxin does gain access to brain tissue and is produced during in vivo infection. The results strongly suggest that this toxin plays a central role in the pathogenesis of A. hydrophila infection. PMID- 8366819 TI - Control of hepatitis B: evaluation of two different vaccinal schedules in newborns from HBsAg negative mothers. AB - 504 healthy infants, born to HBsAg negative mothers from May 1st to December 31st 1991, were randomly allocated to an accelerated (group A) or traditional (group B) immunization schedule. The group A infants were immunized at 4 days, 1 month and 3 months of life with 10 micrograms of recombinant HBV vaccine (Engerix B, SKF) while the group B infants were immunized at 4 days, 1 month and 6 months of life with the same dose of vaccine. One month after the first dose of vaccine, 9.2% of the infants in both groups had an HBsAb serum level > 10 mIU/ml. One month after the booster dose, at 4 months of life for group A and at 7 months for group B, 97.40% and 98.53% of the infants presented a serum level > 10 mIU/ml respectively. None in group A and only 2 patients in group B could be considered non-responders (serum concentration below 2 mIU/ml) and 4 infants in group A and 4 in group B were considered hypo-responders (serum level between 2.1 and 9.9 mIU/ml). Immunogenetic study performed on the 2 non-responders and 6 of the hypo responders, revealed the presence in all but two of the HLA haplotypes, classically involved in the lack of hyporesponsiveness to foreign peptides, namely: HLA-DR7; DQ2, DR4; DQ3, DR15; DQ6 and DR3; DQ2. Surprisingly, 2 hypo responders carried the HLA haplotypes (DR11, DQ7 and DR13, DQ6), usually associated with hyperresponsiveness. Both vaccinal cycles provided evidence that infants respond well to vaccination, started at birth, against hepatitis B virus with a high degree of protection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366820 TI - Rapid methods for microbial diagnosis of mycobacterial infections. AB - The Authors describe their experience in rapid diagnosis of mycobacterial infections using a combination of a radiometric blood culture (Bactec 13 A) and a nucleic acid hybridization system (Gen probe, Accuprobe) to detect and identify Mycobacteria. They found out that a high number of septicaemias in HIV positive patients are due to Mycobacterium avium, while in HIV negative subjects Mycobacterium tuberculosis is the most frequent mycobacterium. PMID- 8366821 TI - Effect of intravenous immunoglobulin on opsonic activity and TNF production in patients at high risk for sepsis syndrome. AB - In a randomized double blind study, we analyzed the efficacy of IVIG in the infectious complications in patients at high risk of developing sepsis syndrome. Two groups of twenty patients were enrolled, one receiving 250 mg/Kg of IVIG on the first and seventh day after admission and the other receiving sterile saline as placebo. Serum samples were drawn before IVIG administration and 24, 48 and 72 hours afterwards. The same schedule was used for patients treated with placebo. Sera pooled from healthy donors served as controls. On all the samples, opsonic and bactericidal activity as well as C3, total IgG and serum TNF content were tested. IVIG did not significantly affect total IgG and C3 content. Similarly, opsonic and bactericidal activity tested against E. coli 06 :K-, E. coli 0111 and SAC I was not modified ranging within HPS values. Furthermore, IVIG administration did not change the TNF level. A lower incidence of bacteremia in IVIG treated patients was observed. PMID- 8366822 TI - Culture filtrates and whole heat-killed Candida albicans stimulate human monocytes to release interleukin-6. AB - The release of interleukin-6 (IL-6) by human monocytes upon stimulation with culture filtrates and heat-killed Candida albicans cells was studied. Two strains of C. albicans (a wild strain CA3 and an agerminative mutant CA2) were cultured overnight at 28 degrees C in complete medium, and 10(6) cells/ml were either filtered at different time points (6, 12, 18, 24, 30 hours) or heat-killed. C. albicans preparations were then added to monolayers of monocytes isolated from healthy donors and incubated at 37 degrees C in 5% CO2 atmosphere. Cell culture supernatants were collected at different time points (every 6 hrs for 30 hrs), and IL-6 content was then measured by immunometric assay. Monocytes stimulated with heat-killed C. albicans cells released IL-6 in the supernatants with values ranging from 59 to 460 pg/ml, that peaked at 24 hrs of incubation. Using heat killed whole cells of C. albicans no major differences were observed between the two strains used in their capacity to induce IL-6. Culture filtrates also stimulated monocytes to release IL-6 and maximal cytokine levels were observed when the monocytes were triggered with filtrates from yeasts cultured for 24 hours. CA2 filtrate induced IL-6 levels to an extent significantly higher than did CA3 filtrate. These data add further evidence to the immunomodulatory properties possessed by structures of C. albicans. PMID- 8366823 TI - Subinhibitory concentrations of antibacterial drugs and Pseudomonas aeruginosa virulence factors. AB - Pseudomonas aeruginosa is an important, opportunistic pathogen responsible for nosocomial infections in the immunocompromised host and resistant to antibacterial drugs. Its pathogenicity is related to many virulence factors such as proteases, alginate, exotoxin A and exoenzyme S. Our previous study showed a down-regulation of some P. aeruginosa virulence factors by subinhibitory concentrations of antibacterial drugs. This study aimed to compare the effects of subinhibitory concentrations of a new difluoroquinolone, PD 131,628, a betalactam, aztreonam and an aminoglycoside, netilmicin. PMID- 8366825 TI - Relationship between Candida albicans and denture stomatitis: a clinical and microbiological study. AB - A study was done on 52 upper denture wearers, randomly selected among the residents of two nursing-homes. The results show that the prevalence of Candida albicans in the denture is significantly higher than that in the mucosa. It was also possible to establish a significant relationship between the clinical patterns and the microbiological findings. A healthy mucosa does not present C. albicans, whereas a diffuse denture stomatitis more often presents the yeast both in the mucosa and in the denture. Finally, diffuse erythema is correlated to continuous denture-wearing, while there is not significant correlation between healthy mucosa and type I denture stomatitis and denture-wearing habits. PMID- 8366824 TI - Outer membrane proteins and lipopolysaccharide changes after exposure of Pseudomonas aeruginosa to antibacterial drugs. AB - Many studies show the low sensitivity of P. aeruginosa to antimicrobial agents, due to the permeability degree of the outer membrane (OM). Since the alterations of porins and lipopolysaccharides (LPS) are responsible for permeability to antibacterial drugs, the aim of this study was to evaluate the sub-M.I.C. effects of different antibiotics on the OM components. The M.I.C.s of five P. aeruginosa strains were determined and sub-M.I.C.s. versus PD-131,628, a new difluoroquinolone, aztreonam and netilmicin were calculated. The OM components were extracted before and after contact with the antibacterial drugs. We noted a decrease in M.I.C. values in two strains, and simultaneously an increase in the 19 and 38 Kd bands after using aztreonam. The M.I.C.s tended to increase in three strains after using netilmicin. The electrophoresis profile showed a decrease in the 38, 41 and 45 Kd bands and in one strain also in the 19 Kd band. The use of the quinolone did not significantly modify the M.I.C. values, although an evident increase in 38 and 41 Kd bands occurred in three strains. LPS alterations were observed with aztreonam and netilmicin, but not when PD 131,628 was used. PMID- 8366826 TI - Assessment of the "Amplicor" PCR test in the diagnosis of Chlamydia trachomatis infection. AB - We compared a commercially available PCR assay (Amplicor, Roche, Switzerland) and tissue culture isolation for the detection of C. trachomatis in urethral and/or endocervical swabs. Of the 200 patients studied (130 men and 70 women) PCR and tissue culture gave concordant results in 199 cases; in one case PCR was positive and culture negative. The Amplicor PCR assay proved fast and sensitive and suitable for routine use in most clinical microbiology laboratories. PMID- 8366827 TI - Partial characterization of HCl heat extracted antigen derived from Fusobacterium necrophorum. AB - The HCl heat extracted antigen derived from Fusobacterium necrophorum was partially purified by CM cellulose column chromatography and treatment by freeze thawing. It demonstrated relatively high enzyme-linked immunosorbent assay values to anti-F. necrophorum sera. In sodium dodecyl sulphate polyacrylamide gel electrophoresis, the partially purified preparation exhibited one definite and two faint bands. The approximate molecular weight of the former was estimated as 16 kD. PMID- 8366828 TI - The effect of an electric field on the release of hexosaminidase in Tetrahymena. AB - The activity of beta-D-hexosaminidase was detected by spectrofluorometry in the growth media of three species of Tetrahymena. The enzyme activity was about six times higher in T. pyriformis compared with the wild cells of T. thermophila, while the MS-1 mutant of T. thermophila manifested very low enzyme activity under the same experimental conditions. An electric field and electrical pulses produced significant though different increases in enzyme activity in media of wild and mutant T. thermophila. In contrast, T. pyriformis responded to the field pulses by decreasing the activity of the enzymes detected in the growth media. PMID- 8366829 TI - Serotype distribution, antimicrobial susceptibility, and clinical character of Streptococcus pneumoniae isolates. AB - Strains of Streptococcus pneumoniae (268 in toto) isolated from different infected sites in patients were serotyped, their susceptibilities to antimicrobial agents were determined, and the laboratory data were correlated with clinical information. The distribution pattern of serogroups and serotypes was different in paediatric patients (< 18 years old) when compared with that of adults. Overall, 91% of the strains were represented in a 23-valent vaccine. Only eight patients received pneumococcal vaccine before infection, and only 18 strains (6.7%) were moderately susceptible or resistant to one or more of the antimicrobial agents tested. Five strains were moderately susceptible to penicillin G, and not one was fully resistant. PMID- 8366830 TI - Ability to assimilate nitrogenous oxides is limited to a few species of yeasts. AB - Several species of yeasts, Saccharomyces cerevisiae, Debaryomyces hansenii, Candida utilis, C. albicans, C. pelliculosa and C. tropicalis, were tested for their ability to utilise different inorganic nitrogen compounds as sole sources of nitrogen, and the results are presented as a function of their growth. All of them grew well on reduced nitrogenous compounds such as ammonium sulphate (ammonia) and L-asparagine, while only C. utilis and C. pelliculosa grew, at a slower rate, on oxidised nitrogenous compounds, nitrate and nitrite. The differences observed in the ability of various yeasts to assimilate the inorganic nitrogen compounds are believed to reflect their individuals abilities to regulate the uptake rates of potentially toxic compounds and keep them in a bound/transient state until reduced to less toxic and more-readily assimilable forms. PMID- 8366831 TI - Factors affecting acetic acid production by yeasts in strongly clarified grape musts. AB - High acetate content in a wine, after strong clarification of the must, is due to depletion in the yeast cells of important metabolites (normally present in non clarified musts) such as metals, amino acids, polyphenolic compounds and unsaturated fatty acids. These substances were added separately to a synthetic medium, comparable in composition to the clarified must, which was then inoculated with a high acetate producer strain. No effects were observed after the addition of various metals and amino acids. The addition of unsaturated fatty acids (Tween 80) caused a significant (p = 0.01) decrease in acetate content. Similar results have been obtained in the presence of polyphenols (catechins and anthocyans): their mechanism of action is probably due to direct inhibition of the enzyme aldehyde dehydrogenase. Control experiments were performed with a low acetate producer strain, and a reduction in acetate content was detected. No differences in the glyceropyruvic metabolism of the two strains was evident. PMID- 8366832 TI - [Asbestos exposure on board ships: a study of the environmental situation on 2 classes of ferryboats]. AB - The article describes the results of a study on contamination by airborne asbestos fibres on board a number of ships belonging to fleets operating from Civitavecchia, a port on the coast of central Italy. Asbestos was widely used throughout the ships as fire- and soundproofing insulation. Samples taken before, during and after removal of the insulation in areas of the ship outside the asbestos removal worksite gave concentration levels that were similar to those observed in other indoor environments (building), varying according to the sample location and the condition of the insulation material. The results are discussed taking into consideration the fact that a ship is also a living environment for crew and passengers. PMID- 8366833 TI - [A comparison between phase-contrast optical microscopy and scanning electron microscopy for the analysis of air-borne asbestos fibers in an office environment]. AB - There is no general agreement on the relationship between results obtained by optical microscopy (PCOM) and electron scanning microscopy (SEM) or electron transmission microscopy (TEM) for airborne asbestos fibres. However, a considerable amount of data has been produced in latter years indicating that a general correlation factor, not differing greatly from unity, can be established between the two analytical techniques if counts are limited to fibres longer than 5 microns. A study was made of the relationship between SEM and PCOM when used simultaneously for determination of background concentrations of asbestos in office buildings. Twenty-four couples of samples were collected in parallel for PCOM and SEM in different locations distributed over the various floors of two buildings containing amosite sprayed on structural parts. Asbestos and total fibre counts by SEM were performed following the Verein Deutscher Ingenieure (VDI) method 3492. For total fibre counts the European PCOM method was mainly used. Discrimination of asbestos from non-asbestos fibres was performed using criteria based on birefringence and morphological characteristics of fibres. Counts included only those fibres longer than 5 microns, diameter less than 3 microns and aspect ratio greater than 3. Both total fibres and asbestos fibres were recorded separately by PCOM and SEM. the arithmetic and geometric means of the ratio between PCOM and SEM were 1.3 and 1.1 respectively for total fibres and 1.2 and 1.1 for asbestos fibres (excluding one outlying value). The regression study showed a significant linear correlation (P = 0.01) with correlation coefficients of 0.84 for asbestos fibres and 0.52 for total fibres. PMID- 8366834 TI - [The cases of accident in the ceramic tile industry in relation to the age and job seniority of the workers]. AB - A study was made of 3,368 workers in 36 ceramic plants in the Scandiano area (Reggio Emilia, Italy) during the year 1990; 403 had an accident during the observation period. The incidence and severity of the accident were correlated to age, job (low, intermediate, high accident risk), duration of employment as at 1.1.1990 (> 24, 12-24, > 24, 12-24, < 12 months, engaged during 1990). Logistic regression analysis, survival analysis and RIDIT analysis were performed using GLIM and EGRET statistical packages. Risk: ORs for intermediate and high-risk jobs vs low-risk jobs were 1.3 (1.0-1.7 95% confidence limits) and 1.7 (1.3-2.3), respectively, adjusted for duration of employment; ORs for the 12-24, < 12 months, engaged during 1990 categories vs the > 24 months category were 1.5 (1.1 2.0), 1.7 (1.3-2.2), 2.1 (1.6-2.8) respectively. Severity: the mean RIDIT of the > 44-year-old vs < 30-year-old workers was 0.6 (0.53-0.67). PMID- 8366835 TI - [Work accidents in the large-scale food distribution sector]. AB - The application of a systematic method of reading accident registers, as has already been experimented in various manufacturing sectors by other authors, is proposed for food supermarkets. The study covered 461 accidents occurring in the five-year period 1986-1990 in 25 food supermarkets in the Milan area. The proposed method is based on the identification of each accident according to the "process/mode of occurrence" data pairs. Subsequent elaboration of these pairs reveals the incidence of accidents and also enables conclusions to be drawn on the main causes that are then useful for the prevention programmes implemented both by local health units and plant management. PMID- 8366836 TI - [Alcohol consumption in some manufacturing activities of Venice: a public health problem]. AB - A total of 1246 workers were interviewed employed in the industrial and urban area of Venice: 91.3% consumed alcoholic beverages, 17.4% of whom exceeded 1 litre of wine per day. Only 15% of the interviewees thought that an acceptable alcohol consumption level should not exceed 1 litre, whereas more than 18% thought that 2 or more litres of wine per day was not harmful. A certain tendency to incorrect knowledge of alcohol and its effects on health was observed. A high consumption of alcoholic beverages was confirmed, mainly depending on the type of work group, a subjective assessment of individual consumption, consumption at work, level of education, duration of consumption, specific information about alcohol. In particular, jobs such as porterage, foundry work, boat piloting, urban refuse collection, road and machine maintenance were associated with alcohol abuse mainly due to the level of education and drinking for pleasure. The paper discusses the role of social dynamics in boosting drinking behaviour and a possible health education policy. The role of occupational health services in community care programmes involving managerial and technical staff is stressed. PMID- 8366837 TI - [Mucocutaneous candidiasis in exposure to biological agents: a clinical case]. AB - Candida albicans, an ubiquity yeast, has several properties which allow it colonize and invade host tissues, often resisting eradication. Acid proteinase is the virulence factor. Bacterial proteinases are widely used in the detergent industry and the role of occupational exposure to enzymes in the development of mucocutaneous candidosis warrants investigation. A case of candidosis is reported in a worker employed in a detergent factory in whom there was no evidence of any kind of immunosuppression. The relationship between occupational exposure and illness is analyzed. PMID- 8366838 TI - A follow-up on workers with predicted individual susceptibility to silicosis. PMID- 8366839 TI - [What kind of health surveillance of workers?]. PMID- 8366840 TI - [Potential for abuse of codeine and dihydrocodeine]. PMID- 8366841 TI - [Vitamin E as a natural antioxidant. Preventive importance and requirement]. PMID- 8366842 TI - [Psychiatric ABC for the pharmacist. Part 1]. PMID- 8366843 TI - [Coronary heart disease. New guidelines of the European Society of Atherosclerosis for prevention]. PMID- 8366844 TI - [Tuberculosis today: vaccination and chemoprophylaxis]. PMID- 8366845 TI - [The nutritional aspects and incidence of obesity and hypertension in a groups of Roman adolescents]. AB - Two-hundred-thirty teenagers of a Roman liceo (specializing in classical studies) have been checked with particular regard to growth, pressure and feeding. The diet of teenagers proved to be particularly unbalanced from the qualitative point of view. There is an excessive intake of fats especially to the detriment of carbohydrates and starches. The incidence of obesity (6.9%) and of hypertension (6%) is not particularly high, probably due to the fact that youngsters at this age "look at themselves in the mirror a lot" for the first case and the second one can be considered as a direct consequence of the first. PMID- 8366846 TI - [An epidemiological study of breast-feeding practice in the referral population of USSL 46 "Alto Mantovano", the Lombardy region. Unita di servizio screening locale]. AB - The aim of this study is to assess the prevalence of breast feeding in the children population of familial advisory bureau in our territory, the reasons for the choice of this kind of nutrition and its duration. The authors also researched if there is some relationship between the choice of feeding and the kind of parturition, mother age, her education and job. The possible influence of the preparatory course of childbirth attendance, mass media and family on this choice was researched to complete the study. PMID- 8366847 TI - [A case of the cardiofacial syndrome (Cayler's syndrome)]. AB - We report a case of cardiofacial syndrome that seems to be genetically transmitted as an autosomal dominant trait. It is characterized by hypoplasia of depressor anguli oris muscle and perimembranous ventricular septal defect. We emphasize the importance of performing diagnostic tests in these patients (cardiac assessment, spinal x-ray, renal echo) in order to rule out associated malformations. PMID- 8366848 TI - [A case of glomerulonephritis in congenital syphilis]. PMID- 8366850 TI - [The transplacental therapy of fetal tachyarrhythmias]. AB - The diagnosis of fetal tachyarrhythmia during a routine ultrasound scan imposes a continuous monitoring of fetal heart function through ECG and M-mode echocardiography. Since fetal dysrhythmia can lead to non-immune hydrops or to fetal death a correct diagnosis and an adequate intrauterine therapy are fundamentally important. The authors report the results obtained through a transplacental therapy with digoxin or with digoxin-verapamil in 8 cases with supraventricular tachyarrhythmia. Digoxin was very successful for conversion in sinus rhythm in 4 cases. The combination digoxin-verapamil led to the conversion in only one case resistant to the digoxin therapy. PMID- 8366849 TI - [The Schonlein-Henoch syndrome with severe multisystemic involvement]. AB - A case of Henoch-Schonlein purpura (HSP) characterized by several unusual complications and exceedingly prolonged course is reported. A 6-year-old boy, hospitalized with a typical clinical picture of HSP, developed after a few days a severe gastrointestinal vasculitis leading to digestive hemorrhages and food intolerance. The treatment included continuous gastrointestinal infusion, parenteral nutrition, and corticosteroids during the exacerbations of symptoms. Intestinal ultrasonography showed diffuse submucous edema and widespread mural hematomas; hydrops of the gallbladder and edematous swelling of the pancreas were also detected. A gastro-duodenoscopy revealed diffuse and severe mucosal vasculitis with ulcers and petechial lesions. One week after admission the occurrence of weight gain, hyponatremia, and hypoprotidemia in the absence of proteinuria suggested a protein-losing enteropathy. The elevation of serum and urine amylases was consistent with pancreatic involvement. The course was characterized by recurrent exacerbations of gastrointestinal manifestations; symptoms subsided slowly to such a degree that oral feeding could be gradually restarted only seven weeks after admission. The use of high-frequency intestinal ultrasonography proved useful and sensitive in monitoring the evolution of intestinal involvement. During hospitalization the child complained of acute painful scrotal swelling. Ultrasonography showed scrotal hemorrhage and testicular swelling but no signs of testicular torsion, thus helping to avoid surgical exploration. In the recovery phase the child complained of colicky abdominal pain with vomiting. A plain abdominal roentgenogram showed bilateral staghorn pelvic urolithiasis. This finding was confirmed by an intravenous pyelography which also revealed a bilateral pyeloureteritis with edema of the ureteral wall and partial stenosis of the lumen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366851 TI - [Clinical evaluation of the tolerance for a soy-based special milk formula in children with cow's milk protein intolerance/allergy (CMPI/CMPA)]. AB - A study aiming to assess the clinical tolerance of a special follow-up soybean milk formula (Neo-Soyal 2) in children with cow's milk protein intolerance or allergy (CMPI/CMPA) has been conducted in 17 infants and children (9 girls and 8 boys) aged from 6 months to 3 years. All the patients had a past history suggestive of CMPI/CMPA and were fed a restricted hypoallergenic diet with a semi elemental formula based on protein hydrolysates. At the time of initiation of the study, all the patients were asymptomatic with normal growth while on a semi elemental diet. The formula with protein hydrolysates was substituted by the test milk (Neo-Soyal 2) and blood samples were taken before and after 2 months. The clinical tolerance to the follow-up soybean formula was considered excellent in 16 children who remained asymptomatic with normal growth velocity. Only one patient developed a severe diarrhoea within 72 hours after introduction of the soybean formula which was stopped. However, after one month he was able to tolerate a certain amount of the soybean milk (240 ml) without symptoms. For all the patients studied, there was no change in the nutritional parameters measured in the blood before and after 2 months of the trial. Likewise, the plasma amino acid levels determined in 2 patients remained unchanged before and after the experimental period. These data indicate that the soybean milk formula used here (Neo-Soyal 2) can be safely given as a substitute of semi-elemental diets during the follow-up of children with CMPI/CMPA after the age of 6 months. PMID- 8366853 TI - Alcohol involvement in pedestrian fatalities--United States, 1982-1992. AB - Pedestrian deaths constitute the second largest category of motor-vehicle-related fatalities (following vehicle-occupant deaths) and account for 14% of all traffic associated deaths and approximately 3% of all traffic-associated injuries. In 1992, 5546 pedestrians were killed and 96,000 were injured in traffic crashes (1,2). Alcohol is an important determinant for both the likelihood of a motor vehicle colliding with a pedestrian and the outcomes for pedestrians in crashes (3). This report summarizes data from the Fatal Accident Reporting System of the National Highway Traffic Safety Administration (NHTSA) on trends in alcohol use in traffic fatalities involving pedestrians in the United States during 1982 1992. PMID- 8366852 TI - Occupational burns among restaurant workers--Colorado and Minnesota. AB - Work-related burns are a leading cause of occupational injury in the United States (1). A substantial proportion of these burns occur among restaurant workers--often affecting adolescents working in fast-food establishments. This report summarizes investigations of restaurant-associated occupational burns by the state health departments in Colorado and Minnesota. PMID- 8366854 TI - Enumerating deaths among homeless persons: comparison of medical examiner data and shelter-based reports--Fulton County, Georgia, 1991. AB - Characteristics of causes of death and mortality patterns in homeless populations have been constrained by limitations in both the accuracy of estimates of the size of the homeless population and enumeration of the number of deaths of homeless persons (1,2). For example, studies of mortality among homeless persons in Fulton County (Atlanta), Georgia, based on medical examiner records estimated approximately 40 deaths of homeless persons annually (1,3); in contrast, a media report based on information supplied by shelters for homeless persons reported 191 deaths of homeless persons in Atlanta during 1991 (4,5). As a basis for improving characterization of mortality patterns in the homeless population of Fulton County, Emory University and CDC assessed the differences in the estimates of deaths among homeless persons that were obtained from medical examiner records and those based on death reports from shelters that are in or adjacent to Fulton County (1990 population: 648,951) during 1991. This report summarizes the findings of that study. PMID- 8366855 TI - Carbon monoxide poisoning associated with a propane-powered floor burnisher- Vermont, 1992. AB - On July 28, 1992, two employees of a pharmacy in Vermont fainted within four hours after arriving for work; at a local hospital emergency department, carbon monoxide (CO) poisoning was diagnosed based on elevated carboxyhemoglobin (HbCO) levels. The pharmacy was evacuated, and the remaining eight employees were transported to the hospital for evaluation. Further investigation by the Vermont Department of Health (VDH) revealed that, on July 24, one of the employees had fainted, but CO poisoning was not suspected, and vasovagal syncope was diagnosed. This report summarizes the investigation of these cases by VDH. PMID- 8366856 TI - Quarterly table reporting alcohol involvement in fatal motor-vehicle crashes. PMID- 8366858 TI - Purification and immunochemical characterization of recombinant and native ragweed allergen Amb a II. AB - The complete sequence of a cDNA encoding Amb a II and its relationship to the Amb a I family of allergens has recently been described [Rogers et al. (1991) J. Immun. 147, 2547-2552; Griffith et al. (1991a), Int. Archs Allergy appl. Immun. 96, 296-304]. In this study, we present results generated with rabbit antipeptide antisera that recognize Amb a II or Amb a I, but not both. The specificity of two anti-Amb a II antipeptide sera, anti-RAE-50.K and anti-RAE-51.K, was verified on Western blots of recombinant Amb a II and Amb aI.1. These two sera, directed against separate regions of the Amb a II molecule, detected three individual 38 kDa Amb a II isoforms on 2D Western blots of aqueous ragweed pollen extract. These Amb a II isoforms have pI in the 5.5-5.85 range and can be easily distinguished from Amb a I isoforms with pI in the 4.5-5.2 range detected by an anti-Amb a I specific peptide antiserum. The Amb a II isoforms have also been individually purified from pollen, positively identified as Amb a II by amino acid sequencing, and visualized as separate bands on IEF gels. An analysis of Amb a II cDNA sequences generated by PCR led to the prediction of three Amb a II isoforms with pI of 5.74, 5.86 and 5.97 that are very similar to the pI deduced from 2D Western blot analysis. Recombinant Amb aI.1 and Amb a II have been expressed in E. coli, purified in their denatured form, and examined by ELISA for their capacity to bind pooled allergic human IgE. Purified native Amb a and Amb a II from pollen were shown to have very similar IgE-binding properties. In contrast, Amb a II had a markedly reduced IgE-binding capacity as compared to Amb a I.1. These data suggest that recombinant Amb a I.1 and Amb a II, isolated in a denatured form, differ significantly in their IgE-binding properties whereas the native molecules isolated from pollen do not. PMID- 8366857 TI - Structure and binding properties of monoclonal antibodies to core histones from autoimmune mice. AB - Histones are frequent targets of self-reactive antibodies during autoimmune syndromes. We report the specificities and V region genes of three IgG anti histone MAbs obtained from autoimmune mice. Each of the MAbs, named LG2-1, LG2-2 and BWA3, is directed against a different determinant located in the basic amino terminal domain of core histones. LG2-1 reacts with a peptide from histone H3 (residues 30-45), LG2-2 recognizes the amino-terminus of H2B (residues 1-13) and BWA3 binds an epitope corresponding to a region of high sequence similarity between H2A and H4 (residues 1-20 and 1-29, respectively). The analysis of their V region sequences indicates that the H chain CDRs of these MAbs are remarkable for the presence of negatively charged amino acid residues that may play a role in the binding to cationic histones. The H chain importance in conferring reactivity to histones is corroborated by the observation that each of the VH gene segments of these MAbs is very similar to VH genes of previously described murine anti-histone antibodies. PMID- 8366859 TI - Efficient complement-mediated lysis of cells containing the CAMPATH-1 (CDw52) antigen. AB - CAMPATH-1 antibodies recognise a unique molecule on human lymphocytes and are unusually efficient at causing cell lysis with homologous complement. They have been successfully used for lymphocyte depletion in vivo in a variety of diseases. The antigen is a small glycosylphosphatidylinositol (GPI)-anchored glycoprotein with a mature peptide comprising only 12 amino acids and one N-linked glycosylation site at Asn3. The antigenic epitope is found in a proteolytic fragment containing the C-terminal tripeptide and the GPI anchor. Both the native and deglycosylated antigen as well as the proteolytic fragment can be reincorporated into various target cells, conferring sensitivity to lysis by CAMPATH-1 antibodies. These results imply that the special feature of the antigen which makes it a good target does not reside in the N-linked sugar or the first nine amino acids: instead they support the hypothesis that the proximity of the antigenic epitope to the cell membrane is more important. PMID- 8366860 TI - The size, shape and stability of complement component C9. AB - Electron microscopy of specimens of C9 tilted through 90 degrees visualized this protein to be a globular ellipsoid with dimensions of 77 x 70 x 52 A. To check the congruence of this observation with physical properties of the molecule, hydrodynamic parameters for C9 were determined. From this work a frictional ratio of 1.32 was calculated. C9 was compared with several other proteins of similar frictional ratios whose tertiary structures are known. All examples found of such proteins whose frictional ratios were between 1.26 and 1.37 are either heart shaped or globular ellipsoids, but none are prolate ellipsoids. By comparison the size and shape of C9 determined by electron microscopy are congruent with its hydrodynamic parameters. Both electron microscopy and physical measurements suggest that the length (110-120 A) of C9 determined by neutron and X-ray scattering experiments is an overestimate. The source of the discrepancy was identified by the demonstration that the high concns of C9 employed in neutron and X-ray scattering work lead to aggregation of the protein. Thus, investigations involving neutron and X-ray scattering were measuring polydisperse solutions of C9. The deduced value of the radius of gyration from that work (33 35 A) is now recognized as being statistical and significantly higher than the correct value of monomeric C9 (26 A), which was calculated from electron microscopy measurements. Also high-resolution electron microscopy clearly visualized poly(C9) to be a barrel-stave construct. These results suggest that monomeric C9 must undergo a major conformational alteration to extend by 55-70 A in order to self-associate laterally in order to fashion the cylindrical poly(C9). PMID- 8366861 TI - Mapping of antigenic determinants of the T. cruzi hsp70 in chagasic and healthy individuals. AB - In the present paper we describe the analysis of the immunological recognition by sera of healthy individuals and chagasic patients of the Trypanosoma cruzi heat shock 70 kDa protein. By a Falcon Assay Screening Test, using as antigen an ATP agarose purified T. cruzi hsp70, it has been found that the sera of infected patients as well as of that of healthy individuals show reactivity against the hsp70 protein but that the reactivity of the sera of patients is in general significantly higher than that of healthy individuals. The analysis of the reactivity of the chagasic sera against a collection of peptides covering 92% of the protein has shown that more than 50% of the peptides gave a positive response but only against a few peptides did we observe high reactivity in a wide spectrum of sera. Only four peptides (numbers 9, 12, 14 and 47) were recognized by all sera tested with high reactivity values. The sera of healthy individuals also showed reactivity against a large percentage of peptides but with lower values. It was observed that particular peptides showing high reactivity against the sera of healthy donors also show high reactivity against patients' sera. However, the general pattern of reactivity against the peptides is different in chagasic and healthy sera. The immunodominant peptides map in the highly conserved as well as in the less conserved part of the hsp70 molecule. The 1/3 C-terminal, being the least conserved part of the molecule, seems to be the least immunogenic. Mapping of the epitopes led to the identification of particular immunogenic motifs within individual peptides. PMID- 8366862 TI - Evidences that syngeneic alpha-type anti-idiotypic antibodies may non competitively inhibit idiotype/oligomeric antigen interactions by affecting idiotype avidity. AB - The effects of syngeneic anti-Id antibodies on the multivalent interaction between human TNF-alpha, a homotrimeric Ag, and an anti-TNF mAb (mAb(1)78) have been studied. Eight anti-mAb(1)78 Ig secreting hybridoma, able to inhibit TNF binding in a competitive or non-competitive mode, have been generated. Two representative clones (mAb(2)1G3 and mAb(2)9F1) were selected for studying the inhibition mechanism of TNF-mAb(1)78 interaction. Idiotype-paratope topography studies indicated that mAb(2)1G3 (IgG2a) and mAb(2)9F1 (IgG1) bind two sterically distinct idiotopes on mAb(1)78 (IgG1) V regions. In particular, mAb(2)1G3 was found to bind an idiotope located within (or spatially close to) the Ag combining site suggesting that competitive inhibition of TNF binding to mAb(1)78 by mAb(2)1G3 occurs through paratope blockade. On the other hand, mAb(2)9F1 recognizes an idiotope located outside the paratope, being able to bind mAb(1)78 even in the presence of saturating amounts of TNF. mAb(1)78-TNF molar ratio in complexes, at stoichiometric equivalence, was unchanged in the presence of a large excess of mAb(2)9F1, suggesting that the functional bivalency of mAb(1)78 was not impaired by this anti-Id antibody. However, bivalent mAb(2)9F1 was able to partially inhibit the binding of bivalent mAb(1)78 to oligomeric TNF in liquid phase as well as in solid-phase assays, whereas no inhibition was observed with monovalent mAb(2)9F1-F(ab) or mAb(1)78-F(ab). This suggests that inhibition is based on a decrease of the avidity of bivalent mAb(1)78 and not on allosteric effects on antigen binding sites. The effect of mAb(2)9F1 on mAb(1)78 arm flexibility and paratope orientation is discussed. In conclusion, the results indicate that anti-Id antibodies may inhibit Ag-antibody multivalent interactions by paratope blockade or by affecting the antibody avidity. PMID- 8366863 TI - The natural autoantibodies system: between hypotheses and facts. PMID- 8366864 TI - Salmonella identification by the polymerase chain reaction. AB - Polymerase chain reaction (PCR) primers for genus specific detection of Salmonella have been selected from a Salmonella-specific fragment of 2.3 kilobases (kb). Due to interserovar sequence diversity within this fragment, primer selection was based on DNA sequence alignment of sequences from 20 different Salmonella serovars. The specific PCR product of 429 base pairs (bp) was formed from 144 of 146 salmonella strains tested (116 of 118 serovars). The two false-negative strains belonged to two different serovars of the rarely isolated subspecies IIIa (monophasic S. arizonae). No product was produced in any of 86 non-Salmonella Enterobacteriacea strains tested, covering 41 species from 21 genera. PMID- 8366865 TI - A combined modified reverse dot-blot and nested PCR assay for the specific non radioactive detection of Listeria monocytogenes. AB - A modified reverse dot-blot assay was developed and used in combination with a nested PCR amplification of hly A for the specific detection of Listeria monocytogenes. The deoxynucleotides and digoxygenin-11-dUTP concentrations in the PCR were optimized for maximal sensitivity and economy. For the dot-blot hybridization, digoxygenin-labelled PCR products were directly spotted on nylon membrane-bound poly-dT tailed capture probes and the signal detection was either colorimetric or chemiluminescent. With crude cell lysates, the total assay could be completed in about 6 h with a detection limit between 2 and 25 colony forming units (cfu) per PCR. The assay was then tested for its applicability to environmental sampling of artificially contaminated aluminum surfaces. For environmental sampling, the assay requires an additional overnight enrichment step and has a sensitivity corresponding to 5 cfu per 25 cm2 of inoculated surface. PMID- 8366866 TI - Detection of mollicute contamination in cell cultures by 16S rDNA amplification. AB - A polymerase chain reaction (PCR) system was developed for the detection of mollicutes as contaminants of cell cultures. By using three oligonucleotides chosen in the 16S rDNA sequences, two sets of primers able to promote amplification of all Mycoplasma and Ureaplasma (molli1-molli2a) or all Acholeplasma (molli1-molli2b) species examined were determined. This PCR system, first applied to experimentally infected Vero cell lines, was then evaluated for the detection of mollicutes in 86 cell culture samples, comparatively to DNA staining, culture and ELISA. The results obtained by the four techniques were in agreement in 82 cases (36 positive, 46 negative). PCR allowed detection of contamination in one and two cases negative by ELISA and culture, respectively, and confirmed questionable results obtained by DNA staining. As described, PCR seems to be a very convenient tool for routine detection of cell culture contaminants. PMID- 8366867 TI - A tool for the molecular analysis of an early lethal disease: slide-PCR in spinal muscular atrophy patients. AB - DNA was recovered from sections of muscle biopsies of 20 spinal muscular atrophy (SMA) patients fixed on microscopic slides and stored from one to 20 years at room temperature. Microsatellite DNA markers tightly linked to the SMA locus were amplified using the polymerase chain reaction (PCR) to obtain specific amplified products. The procedure was successful in all cases, and allowed prenatal diagnosis in one at-risk pregnancy. In our hands this procedure is quick, sensitive and reproducible. PMID- 8366868 TI - Determination of N-myc gene amplification in neuroblastoma by differential polymerase chain reaction. AB - Determination of N-myc gene amplification, a powerful prognostic indicator in the childhood tumour, neuroblastoma, has routinely been performed by Southern analysis. We have developed a differential polymerase chain reaction (PCR) assay, in which the N-myc target gene is co-amplified with a control gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Following electrophoresis, a ratio between the two PCR products within a given DNA sample is then determined by densitometry. This assay was applied to DNA isolated from 32 primary neuroblastoma tumours for which the N-myc status had previously been determined by Southern analysis. Following PCR, samples containing a single copy of the N myc oncogene were clearly distinguishable from samples with N-myc gene amplification, based on an N-myc/GAPDH ratio of below or above 1.0, respectively. Linear regression indicated a highly significant relationship (R = 0.94; P < 0.0001) between N-myc copy number (Southern) and N-myc/GAPDH ratio (PCR). Serial dilution of N-myc amplified DNA with non-amplified control DNA indicated that the PCR assay was sufficiently sensitive to detect two-fold amplification. Moreover, such serial dilution allowed determination of N-myc copy number. The assay, which requires only small amounts of tissue and does not utilize 32P-radioactivity, therefore provides a rapid and sensitive alternative to Southern analysis. PMID- 8366869 TI - A new polymerase chain reaction (PCR) assay for the trinucleotide repeat that is unstable and expanded on Huntington's disease chromosomes. AB - The Huntington's Disease (HD) Collaborative Research Group has recently published the sequence of a new cDNA, IT15, containing a polymorphic trinucleotide (CAG)n repeat that is expanded and unstable on HD chromosomes. There is a correlation between the repeat size and the age of onset of symptoms. The suggested polymerase chain reaction (PCR) assay of the (CAG)n repeat requires unusual reaction components and primer concentrations and the use of 5% polyacrylamide sequencing gels to resolve the amplification products. We present a simple PCR assay that produces a smaller product using standard reaction conditions. This gives better resolution of the (CAG)n expansion observed on HD chromosomes by acrylamide gel electrophoresis and allows sufficient product to be obtained to perform assays using agarose gels. This will allow diagnostic labs to do rapid and accurate presymptomatic testing of HD in high risk families. PMID- 8366870 TI - Experiences on the application of the polymerase chain reaction in a diagnostic laboratory. AB - Double polymerase chain reaction (PCR) assays with nested primers have been applied in a routine laboratory for the diagnosis of herpes-, pesti- and retroviral infections of animals. Various methods and tools have been tested to prevent and to eliminate false positive results as well as to visualize the PCR products (amplicons). The u.v. and DNase treatments proved to be unsuitable for decontamination of PCR mixtures contaminated with amplicons shorter than 380 bp. By constructing special tube-holders and openers, and by applying a simple technique of pipetting, the false-positive PCR results were eliminated. The PCR products were visualized by three simple methods. The solid phase colorimetric method termed 'Detect Immobilized Amplified DNA' (DIANA) has been adapted to microplate. The other method, termed 'Colorimetric Detection Assay on Filter' (CODAF), proved to be very rapid. However, despite these advantages of DIANA and CODAF, henceforward the nucleic acid hybridization methods were found most reliable for safe identification of PCR amplicons. In order to simplify the hybridization, various non-radioactive labelling methods of oligonucleotide probes were compared. Biotinylation at the 5' end by means of oligonucleotide synthesis was the most simple and practical labelling method in this laboratory. The routine applicability of hybridization was further simplified by constructing a robot device, which automatically performs filter-hybridization and subsequently develops the signals derived from the biotinylated hybrids. PMID- 8366871 TI - Increased PCR sensitivity by using paraffin wax as a reaction mix overlay. AB - The use of mineral oil as a reaction mix overlay in conventional PCR may lead to problems. In addition to more difficult handling, traces of mineral oil in amplicon suspensions have been shown to decrease the efficiency of post-PCR manipulations. Commercial alternatives aimed at resolving the problem more than double the cost of an amplification. This is an important drawback when dealing with a large number of clinical samples. The use of inexpensive paraffin wax as a reaction mix overlay eliminated problems associated with the presence of mineral oil while being more practical and safer in handling potentially contaminated clinical samples. Moreover, when used in conjunction with a modified hot start technique, the use of paraffin wax increased the specificity and sensitivity of PCR amplifications over mineral oil in similar hot start conditions. Using the aforementioned method, the increase in specificity and sensitivity has enabled specific detection of viral DNA in clinical samples which the conventional PCR method failed to detect. PMID- 8366872 TI - Language comprehension in ape and child. AB - Previous investigations of the linguistic capacities of apes have focused on the ape's ability to produce words, and there has been little concern for comprehension. By contrast, it is increasingly recognized that comprehension precedes production in the language development of normal human children, and it may indeed guide production. It has been demonstrated that some species can process speech sounds categorically in a manner similar to that observed in humans. Consequently, it should be possible for such species to comprehend language if they have the cognitive capacity to understand word-referent relations and syntactic structure. Popular theories of human language acquisition suggest that the ability to process syntactic information is unique to humans and reflects a novel biological adaptation not seen in other animals. The current report addresses this issue through systematic experimental comparisons of the language comprehension skills of a 2-year-old child and an 8 year-old bonobo (Pan paniscus) who was raised in a language environment similar to that in which children are raised but specifically modified to be appropriate for an ape. Both subjects (child and bonobo) were exposed to spoken English and lexigrams from infancy, and neither was trained to comprehend speech. A common caretaker participated in the rearing of both subjects. All language acquisition was through observational learning. Without prior training, subjects were asked to respond to the same 660 novel sentences. All responses were videotaped and scored for accuracy of comprehension of the English language. The results indicated that both subjects comprehended novel requests and simple syntactic devices. The bonobo decoded the syntactic device of word recursion with higher accuracy than the child; however, the child tended to do better than the bonobo on the conjunctive, a structure that places a greater burden on short-term memory. Both subjects performed as well on sentences that required the ability to reverse work order as they did on sentences that did not require this capacity. These results are discussed in light of a model of the evolution of language that suggests that the potential for language comprehension preceded the appearance of speech by several million years at minimum. The onset of speech is linked to the appearance of fully adapted bipedalism, which necessitated reorientation of the laryngeal tract and made closure of the soft palate possible. For the first time, such closure permitted mammals to easily produce sounds that could be interpreted by the mammalian auditory system in a categorical manner. When these sounds were paired with the previously extant capacity to produce vowels, it became possible to form "bounded vowels" or sound units that could readily be discriminated as units by the auditory system. It is suggested that this physical adaptation allowed the extant cognitive capacity of the hominids to embark on a speech-like mode of communication. PMID- 8366873 TI - Comprehension and production in early language development [see comment]. PMID- 8366874 TI - Kinetics of amorolfine in human nails. AB - Amorolfine penetrates rapidly into the nail after topical application. The kinetics of penetration follow an exponential law as expected, and the level of amorolfine measured in the nail (at least in the upper levels) already exceeds the MIC of most fungi causing onychomycosis after only 24 h of contact. After topical application amorolfine is detectable in the nail earlier and in higher concentrations than terbinafine and itraconazole after oral application. PMID- 8366875 TI - Susceptibility testing of Candida species for fluconazole: the role of buffering in the agar dilution assay. AB - The role of buffering in the determination of the minimal inhibitory concentration (MIC) of fluconazole was studied with Candida species. Agar dilution tests were performed on media (pH 7.25) buffered with either phosphate or morpholinopropane-sulfonic acid (MOPS) or endomethylene-tetrahydrophthalic acid (EMTA), 0.1 mol l-1 each, or on the unbuffered medium. It consisted of casitone and glucose supplemented with FeCl3 and MgSO4. The MICs recorded after 24 h at 37 degrees C extended from 0.1 mg l-1 to > or = 100 mg l-1 on the phosphate and EMTA medium, being concordant on both media. On the MOPS medium and the unbuffered medium the readings were also concordant; the MICs, however, were mostly 25 mg l-1 or higher. This increase of the values--up to six dilution steps -could not be correlated with the amount of acid secreted by the single strains. EMTA proved to be an alternative to phosphate in this system, and because it allows a faster growth of the yeasts it might be superior to phosphate. The concordance of the MIC values in the presence of such different buffer compounds tends to suggest that they indeed indicate the strongest inhibition attainable in vitro by fluconazole. MOPS was confirmed to be of no use in this system. PMID- 8366876 TI - Clinical efficacy and tolerability of saperconazole for tinea of glabrous skin. A report on four cases. AB - In a randomized controlled trial three different treatment protocols with the new broad-spectrum peroral antifungal saperconazole were evaluated. The treatment regimens were as follows: 100 mg per day for 7 days, 200 mg per day for 7 days, 100 mg per day for 14 days. Of four assessable cases of dermatophytosis of glabrous skin treated with one of these three therapeutic regimens, one was cured. In this patient, however, the dermatophytosis relapsed after the end of the observation period, but due to a different microorganism. While partial improvement was seen in the other cases definite cure was not obtained. No adverse events were recorded. PMID- 8366877 TI - Tinea corporis bullosa. AB - The paper reports a case of tinea corporis bullosa in a 63-year-old woman. Near the classical annular lesions on the anterior surface of the left leg, the patient presented frank bullous lesions. Serous fluid from the bulla yielded Microsporum canis, the first report of the association of this fungus with bullous lesions in tinea corporis. The patient was investigated with routine examinations and immunological studies which showed an intense inflammatory process much greater than in usual cases of tinea corporis. PMID- 8366878 TI - Cutaneous pythiosis in horses from Brazil. AB - Equine pythiosis was studied in five animals from two farms located in a swampy region of southern Brazil (Rio Grande do Sul State). Granulomatous lesions exuding necrotic material and containing a central yellow and firm tissue core, the 'kunker', were observed on the top of the nose of one horse, on the abdomen of two horses and on the hind limbs of two other animals. Direct microscopic preparations, histopathological examination of lesion material, and macroscopic and microscopic characteristics of the isolates confirmed the diagnosis of pythiosis. Surgical intervention of the inflammatory processes, intravenous potassium iodide and topical application of copper sulphate were used without success. PMID- 8366879 TI - Chrysosporium gourii Jain, Deshmukh & Agrawal sp. nov. AB - A new keratinophilic species, Chrysosporium gourii, an isolate of cattle farm soil of Sagar, India, is described and illustrated. The differences between this and other similar keratinophilic species of Chrysosporium are discussed. PMID- 8366880 TI - Diagnostic problems with imported cases of mycetoma in The Netherlands. AB - Eight cases of imported mycetomata in The Netherlands are reviewed. Seven of these were cultured; only one isolate, Actinomadura madurae, belonged to a species commonly known as an agent of mycetoma. The remaining strains either belonged to very rare species, such as Phialophora cyanescens, or could not be identified at all. The list of possible agents of mycetoma apparently needs to be expanded. In addition, the concept of endemic occurrence of aetiological agents of eumycetoma needs revision. Divergent saprophytes may be involved which are able to survive in human tissue. PMID- 8366881 TI - Mycetoma: a retrospective study of 41 cases seen in Sao Paulo, Brazil, from 1978 to 1989. AB - Clinical and epidemiological aspects of 41 cases of mycetoma seen in Sao Paulo city from January 1978 to December 1989 are presented. Twenty-eight cases (68%) were caused by actinomycetes, while 13 (32%) were caused by true fungi. In only 22 (78%) actinomycetoma cases was it possible to identify the agent. Nocardia brasiliensis, by far the commonest actinomycete isolated, was responsible for 13 cases. Among eumycetomata, Madurella grisea was isolated from 3 cases, Scedosporium apiospermum from 2 cases, and Madurella mycetomatis from 1 case, and in 7 cases the agent was not identified. Distribution by sex and age was similar to that reported in the literature. Feet and legs were the commonest sites affected. The mean age of actinomycetoma patients was 33.2 years, while patients with eumycetomata were an average of 32.8 years. Mean duration of the disease was 6.8 and 9.8 years respectively. Most patients came from rural areas in the north eastern region of the country and worked as field labourers. Bone involvement was frequent for both actinomycetomata and eumycetomata and was characterized by osteoporosis, periostal reaction and cavitation. The authors' elected treatment consists of combining sulfamethoxazole (800 mg) and trimethoprim (100 mg) with prednisone (10 mg) orally, daily. PMID- 8366882 TI - Exophiala jeanselmei keratitis. AB - We present the case of a 42-year-old Saudi male with a fungal corneal abscess in his left eye. The aetiological agent was found to be the dematiaceous fungus Exophiala jeanselmei. The patient was treated with topical natamycin, miconazole, and also amphotericin B. During the course of the infection corneal perforation occurred which was treated with cyanocrylate glue. Secondary glaucoma resulted from peripheral anterior synechia which necessitated trabeculectomy. At the end of the course the infection was successfully eradicated, the complications were cured, and vision improved from counting fingers in front of the face at presentation to 20/80. There was no recurrence of the infection in a follow-up period of 2 years. PMID- 8366883 TI - Sequence diversity in the intron of the calmodulin gene from Plasmodium falciparum. AB - Sequence variation in the single intron of the calmodulin gene of Plasmodium falciparum has been examined following amplification using the polymerase chain reaction (PCR). The intron has 4 repeating motifs varying in length: 3 of these contain a dinunucleotide repeat, dA-dT, the fourth is a pentameric repeating unit, dA-dT-dA-dT-dT. These DNA polymorphisms can be applied to the study of parasite populations in mixed infections and in strain identification. The function of these repeating motifs is unknown. Computer modelling of the possible intron structures demonstrates that each of these repeating motifs forms individual stem loops such that any changes in repeat number are self compensatory and do not change the overall intron structure. The implications of this sequence variation are discussed. PMID- 8366884 TI - Two alleles of the 175-kilodalton Plasmodium falciparum erythrocyte binding antigen. AB - EBA-175, erythrocyte binding antigen 175, is a 175-kDa antigen of Plasmodium falciparum which has been shown to be involved in the recognition of erythrocytes by merozoites and may be involved in the process of erythrocyte invasion. Invasion of erythrocytes by Camp strain merozoites is inhibited by pre-treatment of red blood cells by EBA-175 from the heterologous strain, FCR-3. The sequence of the Camp strain has been published and we report here the sequence of the FCR 3 strain. The sequences are nearly identical except for a 423-bp segment in the FCR-3 strain, F-segment, that is not found in the Camp strain and a 342-bp segment, C-segment, present in the Camp strain but not in the FCR-3 strain. The locations of these two segments are different in Camp and FCR-3 EBA-175 genes and there is little DNA or amino acid sequence homology between them. The essentially dimorphic alleles, F-segment and C-segment, are conserved in all isolates examined to date. Evidence of genetic cross-over between the FCR-3 and the Camp EBA-175 genes was not observed in the analysis of a limited number of wild isolates. The continued study of the biological relevance of these sequence divergences in EBA-175 may further elucidate the sequence of events resulting in merozoite invasion of erythrocytes. PMID- 8366885 TI - The gene coding for the major sheath protein of Litomosoides carinii microfilariae, gp22, is transcribed in oocytes and embryonic cells. AB - The transcription and translation of the gene encoding gp22, a major constituent of the microfilarial sheath of the filarial parasite Litomosoides carinii were studied by in situ hybridisation and immunohistology. Transcription of the gp22 gene is confined to oocytes and embryos in the reproductive organs of adult female worms. It starts in oocytes in the rhachis zone, is maximal in multicellular embryos and decreases slowly as the microfilariae develop. Blood microfilariae lack the gp22 transcript. The gp22 gene product is first detectable in parasites recovered on day 32 post infection. Expression of gp22 begins in multicellular embryos in the uteri of mature female worms and can be detected in all further developed intrauterine stages. The gp22 gene product appears to be exported by the embryonic cells and becomes integrated into the sheath where it may contribute to the flexibility of the latter structure. PMID- 8366887 TI - Molecular characterisation of beta-tubulin genes present in benzimidazole resistant populations of Haemonchus contortus. AB - A beta-tubulin isotype 1 gene, gru-1, from a benzimidazole (BZ)-resistant population of the nematode parasite, Haemonchus contortus, was cloned and sequenced. The predicted gene organisation showed 10 exons and 9 introns, one of which was H. contortus specific. Using probes and restriction sites selected from this sequence, restriction maps were constructed from and around beta-tubulin genes of 3 BZ-susceptible and 7 BZ-resistant populations. There was a reduction in beta-tubulin isotype 1 genes to usually one, in BZ-resistant populations. So, our previously reported reduction of beta-tubulin probe-reactive RFLP fragments in resistant populations correlated with the reduction of beta-tubulin isotype 1 genes. The beta-tubulin isotype 1 gene present on the apparently selected fragment and was not always the same, and the geographical origin of the resistant populations indicated independent development rather than geographical spread of the resistant populations. The beta-tubulin genes on the apparently selected fragments were transcribed and processed to mRNA using the nematode specific trans-spliced leader (SL1). Comparison of the derived amino acid sequence of gru-1, with known sequences from a susceptible population, identified 3 mutations that could be involved in BZ resistance. PMID- 8366888 TI - Molecular cloning, complete sequence of the small subunit ribosomal RNA coding region and phylogeny of Toxoplasma gondii. PMID- 8366886 TI - Isolate-specific parasite antigens of the Babesia bovis-infected erythrocyte surface. AB - Bovine erythrocytes taken from in vitro cultures of Babesia bovis parasites from Mexico and the United States were assayed for the presence of new epitopes on the erythrocyte surface. New surface-exposed epitopes were detected by means of a whole-cell antigen capture assay. These epitopes were subsequently demonstrated only on infected erythrocytes by immunofluorescence staining of intact, living cells. Parasite-synthesized antigens were identified on each isolate using a surface-specific immunoprecipitation technique to analyze metabolically-labeled infected erythrocytes. In the Mexico isolate these antigens were 120 kDa and 107 kDa, whereas in the United States isolate polypeptides of 135, 120 and 107 kDa were detected. In each of these assays, reaction of immune sera with the infected erythrocyte surface was found to be isolate-specific. PMID- 8366889 TI - SA85-1 proteins of Trypanosoma cruzi lack sialidase activity. PMID- 8366890 TI - Inhibition of Plasmodium falciparum hypoxanthine-guanine phosphoribosyltransferase mRNA by antisense oligodeoxynucleotide sequence. PMID- 8366891 TI - Molecular cloning and characterization of an Echinococcus granulosus cDNA encoding malate dehydrogenase. PMID- 8366892 TI - Genetic exchange in Trypanosoma brucei: selection of hybrid trypanosomes by introduction of genes conferring drug resistance. AB - Genetic exchange in Trypanosoma brucei ssp. can occur when 2 different strains are cotransmitted through the tsetse fly vector. We have introduced heterologous genes for drug resistance (neo or hph) into parental trypanosome lines by electroporation. Drug resistant lines were then crossed in vivo in the fly or in vitro. Hybrids were subsequently selected by double drug resistance. Analysis of trypanosomes from both fly midguts and salivary glands showed the latter to be the probable site of genetic exchange. This is one of the first applications of reverse genetics to a longstanding problem in parasite biology. PMID- 8366893 TI - The gamma-tubulin gene of the malaria parasite Plasmodium falciparum. AB - By screening of cDNA and genomic libraries of Plasmodium falciparum with a DNA probe derived from the cognate beta-tubulin gene, gene Pf gamma tub has been identified that codes for gamma-tubulin, a newly discovered member of the tubulin superfamily that is indispensible for nuclear division and microtubule assembly [12]. Gene Pf gamma tub is not interrupted by introns and only present as a single-copy in the parasite genome. Its encoded amino acid sequence (452 amino acids; M(r) 50,560) has a 63% similarity to the gamma-tubulins encoded by Aspergillus nidulans, Schizosaccharomyces pombe, Drosophila melanogaster, Xenopus laevis and Homo sapiens. This figure is significantly (approx. 8%) lower than the average identity between the gamma-tubulins of the latter five species suggesting that during evolution the genes have been exposed to different selection pressures. The identity of gamma-tubulin to the Plasmodium falciparum encoded alpha- and beta-tubulins is 30 and 33%, respectively. PMID- 8366894 TI - Pathways of pyrimidine nucleotide biosynthesis in gravid Angiostrongylus cantonensis. AB - The incorporation of radioactive precursors into pyrimidine nucleotides via de novo and salvage pathways was measured in gravid Angiostrongylus cantonensis by HPLC and thin-layer chromatography. 14C-labelled orotate, uridine, uracil and deoxyuridine were traced to UMP, UDP, UTP, UDP-glucose, dTMP, CMP, CDP and CTP. 3H-labelled cytidine was also incorporated into both uracil and cytosine nucleotides in a ratio of 2:1. Cytosine was a major end-product for all the precursors. Cytosine nucleotides were probably formed from UTP by the action of CTP synthetase whose activity in crude cell-free extract was 31.5 +/- 4.9 pmol min-1 (mg protein)-1. It was dependent on glutamine, ATP and GTP and was inhibited by CTP. The total amount of pyrimidine nucleotides formed from uridine was 3 times of that from uracil. The presence of uracil in the metabolism of uridine indicates that UMP is formed by uracil phosphoribosyltransferase as well as by uridine kinase. UMP is a key intermediate for cytidylate and thymidylate biosynthesis in the gravid worms. PMID- 8366895 TI - Phylogenetic position of the genus Perkinsus (Protista, Apicomplexa) based on small subunit ribosomal RNA. AB - Parasites of the genus Perkinsus destroy marine molluscs worldwide. Their phylogenetic position within the kingdom Protista is controversial. Nucleotide sequence data (1792 bp) from the small subunit rRNA gene of Perkinsus sp. from Anadara trapezia (Mollusca: Bivalvia) from Moreton Bay, Queensland, was used to examine the phylogenetic affinities of this enigmatic genus. These data were aligned with nucleotide sequences from 6 apicomplexans, 3 ciliates, 3 flagellates, a dinoflagellate, 3 fungi, maize and human. Phylogenetic trees were constructed after analysis with maximum parsimony and distance matrix methods. Our analyses indicate that Perkinsus is phylogenetically closer to dinoflagellates and to coccidean and piroplasm apicomplexans than to fungi or flagellates. PMID- 8366896 TI - Random amplified polymorphic DNA analysis of Trypanosoma cruzi strains. AB - DNA extracted from 32 isolates of Trypanosoma cruzi was subjected to polymerase chain reaction amplification using 4 arbitrary primers resulting in relatively complex DNA profiles that include polymorphic markers known as random amplified polymorphic DNAs (RAPDs). The RAPD profiles of 18 strains belonging to zymodeme 1 (Z1) collected from various regions of South America exhibited a consistant pattern and 59 (59%) of the bands produced were present in all Z1 strains. A similar level of consistency was seen in the number of bands shared between 5 Z2 strains, 4 ZB strains and 2 ZC strains. A phenetic analysis of the 5 most different Z1 strains based on band sharing showed that their interrelationships mirrored their geographical origin. Comparison of the RAPD profiles of strains from different zymodemes showed that less than 7% of bands of strains in one zymodeme are present in strains of another zymodeme. Analysis of band sharing using bands present in all strains of a given zymodeme showed ZB and ZC to be closely related and Z1 and Z2 to form distinct groups. PMID- 8366897 TI - Structure of the gene encoding a putative Schistosoma mansoni tegumental antigen precursor. AB - In order to obtain the complete gene encoding the putative precursor of a 15-kDa Schistosoma mansoni tegumental antigen (Sm15), two cDNAs (A70 and A184) and two fragments of independent genomic clones were subcloned and sequenced. The collated sequence contains 4700 nucleotides and represents the full length open reading frame of the gene, encoding a protein of 1032 amino acids with a calculated molecular mass of 116,900. Thus, the gene encodes a much longer protein than that identified in the tegumental membranes, suggesting that it encodes a precursor that is subsequently highly processed. A 964-bp region composed of 5 closely related repeats was found to be present within the translated frame. The predicted protein is highly acidic and there is no indication of hydrophobic domains that may represent transmembrane regions or indicate attachment of a GPI anchor. The coding region has no homologies in the currently available data bases. In the 5' non-transcribed area a copy of the SM alpha repeat family is present. The coding region is preceded by putative CCAAT and TATA boxes that may be involved in the control of expression. PMID- 8366898 TI - Transport of D-fructose and its analogues by Trypanosoma brucei. AB - Kinetic parameters for entry of D-fructose into Trypanosoma brucei brucei have been determined. The net uptake of D-fructose was found to be rapid and occurred at a rate which was comparable with that observed for uptake of D-glucose. The Km and Vmax were 3.91 +/- 1.58 mM and 69.1 +/- 7.2 nmol min-1 (mg protein)-1. D Fructose was metabolized to pyruvate under aerobic conditions and to pyruvate and glycerol under anaerobic conditions in a manner similar to D-glucose. Comparisons of the kinetic parameters for D-fructose transport and metabolism indicated that uptake was rate limiting. Inhibition constants (Ki) for inhibition of 6-deoxy-D glucose by D-fructose and D-fructose transport by 6-deoxy-D-glucose were consistent with the Km values for these two substrates. These interactions indicate that D-fructose and 6-deoxy-D-glucose share a single common transporter. 1,5-Anhydro-D-glucitol and 1,5 anhydro-D-mannitol (the fused pyranose ring analogues of D-glucose and D-mannose) have been found to interact well with the transporter, while L-sorbose (a D-fructose analogue with a pyranose ring) had only low affinity. However, 2,5-anhydro-D-mannitol (a fused furanose ring analogue of D-fructose) inhibited both 6-deoxy-D-glucose and D-fructose transport with a Ki of approx. 0.8 mM. The high affinity for 2,5-anhydro-D-mannitol (2 deoxy-D-fructofuranose) indicates that D-fructose is transported in the furanose ring form.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366899 TI - The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. AB - BACKGROUND: Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis. METHODS: We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration. RESULTS: As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients. CONCLUSIONS: Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition. PMID- 8366900 TI - Images in clinical medicine. Superior vena cava syndrome. PMID- 8366901 TI - Social and economic consequences of overweight in adolescence and young adulthood. AB - BACKGROUND AND METHODS: Overweight in adolescents may have deleterious effects on their subsequent self-esteem, social and economic characteristics, and physical health. We studied the relation between overweight and subsequent educational attainment, marital status, household income, and self-esteem in a nationally representative sample of 10,039 randomly selected young people who were 16 to 24 years old in 1981. Follow-up data were obtained in 1988 for 65 to 79 percent of the original cohort, depending on the variable studied. The characteristics of the subjects who had been overweight in 1981 were compared with those for young people with asthma, musculoskeletal abnormalities, and other chronic health conditions. Overweight was defined as a body-mass index above the 95th percentile for age and sex. RESULTS: In 1981, 370 of the subjects were overweight. Seven years later, women who had been overweight had completed fewer years of school (0.3 year less; 95 percent confidence interval, 0.1 to 0.6; P = 0.009), were less likely to be married (20 percent less likely; 95 percent confidence interval, 13 to 27 percent; P < 0.001), had lower household incomes ($6,710 less per year; 95 percent confidence interval, $3,942 to $9,478; P < 0.001), and had higher rates of household poverty (10 percent higher; 95 percent confidence interval, 4 to 16 percent; P < 0.001) than the women who had not been overweight, independent of their base-line socioeconomic status and aptitude-test scores. Men who had been overweight were less likely to be married (11 percent less likely; 95 percent confidence interval, 3 to 18 percent; P = 0.005). In contrast, people with the other chronic conditions we studied did not differ in these ways from the nonoverweight subjects. We found no evidence of an effect of overweight on self esteem. CONCLUSIONS: Overweight during adolescence has important social and economic consequences, which are greater than those of many other chronic physical conditions. Discrimination against overweight persons may account for these results. PMID- 8366902 TI - Acute monoarthritis. PMID- 8366903 TI - Treatment of Parkinson's disease. PMID- 8366904 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-1993. An 83-year-old woman with hypertension, sudden severe back pain, and anuria. PMID- 8366905 TI - The diabetes control and complications trial. Implications for policy and practice. PMID- 8366906 TI - Obesity and socioeconomic status--a complex relation. PMID- 8366907 TI - My life at the Journal, 1961-1993. PMID- 8366908 TI - Hormone replacement and cardiovascular risk factors. PMID- 8366909 TI - Hormone replacement and cardiovascular risk factors. PMID- 8366910 TI - Hormone replacement and cardiovascular risk factors. PMID- 8366911 TI - Hormone replacement and cardiovascular risk factors. PMID- 8366912 TI - Single-drug therapy for hypertension in men. PMID- 8366913 TI - Single-drug therapy for hypertension in men. PMID- 8366914 TI - Single-drug therapy for hypertension in men. PMID- 8366915 TI - Combination chemotherapy for ITP. PMID- 8366916 TI - Immunization of adults. PMID- 8366917 TI - Immunization of adults. PMID- 8366918 TI - Immunization of adults. PMID- 8366919 TI - Physicians' autonomy. PMID- 8366920 TI - Physicians' autonomy. PMID- 8366921 TI - The American health care system. Teaching hospitals. PMID- 8366922 TI - The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. AB - BACKGROUND: Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. METHODS: A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. RESULTS: In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. CONCLUSIONS: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM. PMID- 8366925 TI - Our violent world. PMID- 8366924 TI - Nursing and health care reform. PMID- 8366923 TI - Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team. AB - BACKGROUND: In patients with the acquired immunodeficiency syndrome (AIDS), toxoplasmic encephalitis is usually a presumptive diagnosis based on the clinical manifestations, a positive antitoxoplasma-antibody titer, and characteristic neuroradiologic abnormalities. A response to specific therapy helps to confirm the diagnosis, but it is unclear how rapid the response should be. We studied the course of patients treated for acute toxoplasmic encephalitis and evaluated objective clinical criteria for this empirical diagnosis. METHODS: A quantifiable neurologic assessment was used prospectively to evaluate the clinical outcome of patients with AIDS and toxoplasmic encephalitis who were treated with oral clindamycin (600 mg four times a day) and pyrimethamine (75 mg every day) for six weeks. RESULTS: Thirty-five of 49 patients (71 percent) responded to therapy, and 30 of these (86 percent) had improvement by day 7. Thirty-two of those with a response (91 percent) improved with respect to at least half of their base-line abnormalities by day 14. Improvement in neurologic abnormalities within 7 to 14 days after the start of therapy was strongly associated with the neurologic response at 6 weeks. The four patients in whom treatment failed and the two patients with lymphoma had progressing neurologic abnormalities or new abnormalities during the first 12 days of therapy. Nonlocalizing abnormalities (headache and seizure) improved regardless of the clinical outcome. CONCLUSIONS: Oral clindamycin and pyrimethamine are an effective treatment for toxoplasmic encephalitis. Patients who have early neurologic deterioration despite treatment or who do not improve neurologically after 10 to 14 days of appropriate antitoxoplasma therapy should be considered candidates for brain biopsy. PMID- 8366927 TI - Disadvantaged professionals: implications for education and practice. PMID- 8366928 TI - Primary care in the emergency room: a collaborative model. AB - Emergency rooms have become primary care centers for a large portion of the population. Unfortunately, most are neither designed nor appropriately staffed to deliver first-line, continuous, comprehensive, family-oriented, and self actualizing care. This paper describes a nurse-managed collaborative primary care practice model that has been functioning for 8 years in an inner city emergency department. PMID- 8366926 TI - Nurse manager characteristics and skills: curriculum implications. AB - If one accepts the premise that all nurses need knowledge of management and leadership, then schools of nursing need to design their curriculum to provide administrative content and learning experiences to adequately prepare nurses for leadership positions. This study assays the opinions of nurse unit managers about the relative importance of different characteristics and skills in effective job performance. A sample of 73 unit managers from six hospitals and two community health agencies ranked human relations and communication skills as most important. Nursing knowledge and clinical skills were ranked second. Experienced managers thought political savvy and business or management skills were more important than did novice managers. The results of this study are discussed in relation to curriculum issues in nursing management at both the baccalaureate and the graduate level. PMID- 8366929 TI - Informed consent: it's more than just a signature on paper. PMID- 8366930 TI - The effect of a preceptorship on nursing performance. AB - The purpose of this quasi-experimental study was to determine the effectiveness of a preceptorship program in increasing the nursing performance of the new graduate. Before and immediately after participating in a 5-week preceptorship the students completed a background data sheet and Schwirian's Six Dimension Scale of Nursing Performance questionnaire. The findings indicated that in all areas measuring frequency of experiences, the students perceived themselves as having performed nursing activities more frequently as a result of the preceptorship. There were no significant changes in the students' perception of their previous preparation. They were equally satisfied about their academic background before and after the preceptorship. Only one nursing indicator, teaching/collaboration, measured a decrease in the quality of performance. All other indicators showed that, from the students point of view, there was an increase in the quality of their nursing performance. The positive trend of the results indicates to the investigators that there was an increase in the effectiveness of the students nursing performance following the preceptorship experience. PMID- 8366931 TI - Continuing nursing education: why don't nurses go? Why don't they use what they learn? AB - There are barriers that block nurses from participating in continuing nursing education (CNE) and from using what they learn when they do participate. This article describes the problems nurses experience in going to, and using what they learn from, CNE. Possible causes for the barriers, and steps to take to surmount them, are discussed. This information has implications for human and financial resource management, staffing and scheduling, staff development, policy regulations, economics, and professional trends. PMID- 8366932 TI - Developing a tool to measure functional changes in advanced dementia. AB - The purpose of this study was to develop a valid and reliable tool to measure functional change in older persons with moderate to severe dementia. The process was a collaborative one, drawing on the skills of both nurse researchers and clinicians. In Phase I of this study, 20 nursing assistants and 3 licensed nurses volunteered as subjects to develop the new scale. Phase II of the study involved 27 subjects with a known diagnosis of dementia to test the scale's interrater reliability and criterion validity. The results demonstrated significant correlation among the raters and between the instruments. The investigators reported promising results from both the method of using staff expertise in scale development and the scale itself. PMID- 8366934 TI - [The CBS Health Survey (Central Bureau for Statistics)]. PMID- 8366933 TI - [Fever of unknown origin; the importance of 'vigorous' observation]. PMID- 8366935 TI - [Digital lung angiography using a flow-directed balloon catheter in the diagnosis of pulmonary embolisms]. PMID- 8366936 TI - [Vaccination against mumps successful]. PMID- 8366937 TI - [Laparoscopy useful in the diagnosis and surgery of acute appendicitis]. AB - The value of diagnostic laparoscopy was evaluated in 74 patients who had clinical signs of acute appendicitis. The average age was 27 years (5-67). The laparoscopically determined degree of inflammation was compared with the results of histologic examination, and the results of laparoscopic appendectomy were evaluated. In 6 patients laparoscopic appendectomy was not performed, because of infiltrative disease (twice), twisted ovary, ovulatory bleeding, enteritis and partially incarcerated inguinal hernia. In 2 patients suffering of acute appendicitis conversion to laparotomy was necessary because of obscured anatomy. On 57 out of 68 patients who underwent appendectomy, the laparoscopic findings were in accordance with histologic examination; i.e. 54 times acute appendicitis and 3 times appendix sana. In 7 patients the appendix was classified as inflamed during laparoscopy, histological examination revealing lymphoid hyperplasia or a subacute inflammation. In 4 patients with a laparoscopically normal appendix, inflammation was seen histologically. The average operation time was 29 minutes and the average postoperative hospital stay was 4 days. Three complications occurred: an inflammatory mass developed in 2 patients post-operatively and I patient had a hematoma in the trocar puncture site and a wound abscess developed. Laparoscopy is an aid in diagnosing appendicitis, and may prevent unnecessary appendectomy. If inflammation is established appendectomy can be performed safely and effectively. PMID- 8366938 TI - [Secondary cases of meningococcal disease in The Netherlands, 1989-1990; a reappraisal of chemoprophylaxis]. AB - OBJECTIVE: To assess the secondary attack rate (SAR) of meningococcal disease among the household contacts of primary patients and to describe the use of chemoprophylaxis in the Netherlands. DESIGN: Descriptive, nation-wide survey. METHODS: Information was collected of patients with meningococcal disease, reported between April 1st, 1989 and April 30th, 1990, and their household contacts. A household contact suffering from meningococcal disease between 24 hours and 1 month after hospital admission of the primary patient, was considered to be a secondary case. Chemoprophylaxis was considered appropriate if rifampicin or minocycline had been prescribed to all household contacts within a maximum of one day after admission of the primary patient. RESULTS: There were 5 secondary cases (SAR: 0.3%). Chemoprophylaxis was prescribed to 627 of 1130 household contacts (55%). Of those the prophylaxis was considered appropriate in 46%. 2 secondary cases were not given any prophylaxis, 2 received penicillin and 1 rifampicin. Of the primary patients, 6% were given prophylaxis during their hospital stay. All meningococci, isolated from pairs of secondary and primary patients, were rifampicin sensitive. CONCLUSIONS: The SAR of meningococcal disease in the Netherlands is similar to that in other countries. Although prescription of chemoprophylaxis is not recommended by the government, it is prescribed to 55% of the household contacts, and in almost half of these instances it was considered to be appropriate. Chemoprophylaxis is rarely prescribed to primary patients. Recommendations concerning chemoprophylaxis in the Netherlands are in need of reappraisal. Based on the results from this study and the literature, the prescription of chemoprophylaxis to all household contacts of a patient with meningococcal disease, and to the index patient, is recommended. PMID- 8366939 TI - [Blepharospasm; results of treatment with botulin]. AB - OBJECTIVE: Discussion of clinical symptoms and differential diagnosis of blepharospasm and treatment with botulinum A toxin. Blepharospasm is an involuntary spasmodic contraction of the eyelids. Within a few years 35%-70% of the patients becomes severely disabled. DESIGN: Prospective, open study. SETTING: Academical Medical Centre, Amsterdam. METHOD: In the period 1985-1992 we have seen 85 patients with blepharospasm. Of these 69 were treated with botulinum toxin, a total of 436 treatments, with a mean dose of 25 IU for each eye. RESULTS: The cause of blepharospasm was unknown in 71 patients. Secondary blepharospasm occurred in: peripheral facial palsy (one patient), herpes zoster infection of the trigeminal nerve (2), brain infarct (1), use of neuroleptics (2), progressive supranuclear palsy (2), Shy-Drager syndrome (1), kernicterus (1), and morbus Sjogren (4). There were 18 patients with autoimmune diseases. 77 (91%) patients had a (very) severe form of blepharospasm. Electromyographic registration revealed a dysfunction of M. levator palpebrae in 7 patients. More than 70% of the patients were free of symptoms for a mean period of two months after each treatment. Local side effects were seen in 61 (14%) of the 436 treatments: ptosis, haematoma, dry eyes, and diplopia. CONCLUSION: Blepharospasm is a disabling disease and occurs sometimes in association with other neurological and ophthalmological diseases. Botulinum A toxin is a safe and effective therapy. Electrophysiological investigation is important in the differential diagnosis; it is unnecessary to do CT or MRI routinely. PMID- 8366940 TI - [Angio-immunoblastic lymphadenopathy]. AB - Angioimmunoblastic lymphadenopathy is a rare lymphoproliferative disease with a poor prognosis. We saw a 24-year-old female patient with a fulminant evolution of an angioimmunoblastic lymphadenopathy, possibly a recurrence after a 10 years remission. PMID- 8366941 TI - [Occupational diseases in The Netherlands; time for consolidation of forces]. PMID- 8366942 TI - [Why was the dosage of proguanil doubled in malaria prophylaxis?]. PMID- 8366943 TI - [Post-pharyngitis sepsis caused by Fusobacterium necrophorum: Lemierre's syndrome]. PMID- 8366944 TI - [Abdominal aortic aneurysm: screening and treatment]. PMID- 8366945 TI - [Abdominal aortic aneurysm: screening and treatment]. PMID- 8366946 TI - [Farmacotherapeutisch Kompas 1993]. PMID- 8366947 TI - [Use of language in relation to public health research and education]. PMID- 8366948 TI - [Pain in the upper abdomen caused by pulmonary embolism]. PMID- 8366949 TI - [Irradiation for pain in cancer patients: the sooner the better]. PMID- 8366950 TI - [More pain due to pain treatment]. PMID- 8366951 TI - [Fibromyalgia in the light of current pain models]. PMID- 8366952 TI - [Secondary prevention of chronic low back pain: a behavior-oriented approach]. PMID- 8366953 TI - [Rabies and vaccination in The Netherlands]. PMID- 8366954 TI - [Ascending phlebothrombosis]. AB - Ascending phlebothrombosis of the lower extremities can have serious consequences if not identified at an early stage. In the Academic Hospital of the Free University, Amsterdam, 18 patients with this disease were seen in the period 1980 1991. Treatment should be aimed at preventing progression of the disease to the deep venous system. This may necessitate ligation and dissection of the V. saphena magna in the groin. Usually conservative treatment will do, provided regular follow-up is performed to see whether progression has taken place to the hiatus saphenus or the popliteal fossa. As the disease has usually progressed further than the clinical signs indicate, duplex scanning should be used in case of doubt. Progression to the deep system should immediately be treated surgically. PMID- 8366955 TI - [A Dutch family with familial Mediterranean fever]. AB - Familial mediterranean fever (or recurrent hereditary polyserositis) is a genetic disorder with an autosomal recessive pattern of inheritance which occurs mostly in patients with eastern Mediterranean origin. Two Dutch patients are described, a 25-year-old women and her 58-year-old father, who suffered from recurring abdominal complaints, fever, and increased erythrocyte sedimentation rate, without evidence of Middle Eastern ancestry or hyperimmunoglobulinemia D. PMID- 8366956 TI - [Chromosome translocation in a DES-daughter: an incidental finding?]. PMID- 8366957 TI - [The diagnosis of spondylodiscitis]. PMID- 8366958 TI - [Cumulative meta-analysis as ultimate truth]. PMID- 8366959 TI - [Meta-analysis: the art of the systematic overview]. PMID- 8366960 TI - [Treatment possibilities in basal cell carcinoma]. PMID- 8366961 TI - [Attention in the medical curriculum for the sequelae of DES administration]. AB - There is still a lack of knowledge among physicians with respect to epidemiology, diagnosis, treatment and psychology of the former use of diethylstilboestrol (DES). A questionnaire was sent to 24 educational representatives of eight departments of general practice and 8 of gynaecology asking about the DES education programme in their departments. Response was 100%. Three of 8 general practice departments had a DES education programme, and all 8 gynaecology departments. With respect to epidemiology, diagnosis, treatment and psychology, the educational effort ranged from 50% to 75%, from 25% to 50%, and from 21% to 46% of the departments giving information regarding DES daughters, DES mothers, and DES sons respectively. The medical education with respect to DES depended much on the personal opinion and involvement of the individual teacher. Training of medical students with respect to the DES problem should be an integral part of preclinical medical education. PMID- 8366962 TI - [Randomized clinical trials in the Nederlands Tijdschrift voor Geneeskunde]. AB - OBJECTIVE: To collect all randomized clinical trials (RCT) published in the Nederlands Tijdschrift voor Geneeskunde (Ned Tijdschr Geneeskd) in order to present them to the Cochrane Centre, Oxford, United Kingdom, to be included in the international database of RCT's, which will be used to perform meta-analyses. DESIGN: Retrospective bibliometric study. SETTING: Editorial office of Ned Tijdschr Geneeskd. METHOD: All original papers (OP), published between the May 1st, 1948 and May 1st, 1993 were studied. Papers were selected that met the criteria for RCT: randomization or the similar assignment of patients to different treatment groups. RESULTS: Of 6820 OP 259 (3.8%) were selected. In 69 (26.6%) randomization seemed to be performed correctly and in 20 (7.7%) randomization was not correct; in 170 (65.6%) there was no randomization. In the period May 1st, 1948 till May 1st, 1968 24 RCT's were published, in the period May 1st, 1973 till May 1st, 1993 60. Most RCT's (78%) describe the effects of pharmaceutical treatment. CONCLUSION: RCT's as such were difficult to recognize in Ned Tijdschr Geneeskd. Over the years there was an increase in the number of published RCT's. The problems we found with the design of RCT's and randomization are still current. An international register of published and/or planned RCT's, as envisaged by the Cochrane Centre, will make it easier to carry out meta analyses. PMID- 8366963 TI - [The treatment of 12 HIV-infected children with zidovudine]. AB - 12 HIV-infected children were treated with a high dose of zidovudine (800/mg/m2/day) during a mean follow up period of 18 months. After starting treatment with zidovudine there was a subjective improvement and an increase in body weight, and a significant decline in serum HIV-antigenemia (p < 0.01) and serum IgG levels (p < 0.05). Zidovudine was generally well tolerated but there was serious hematological toxicity. In 9 patients (75%) dose reduction was necessary because of severe anemia (3 patients) or leucopenia (6 patients). Because of the high incidence of these side effects the starting dose of zidovudine was reduced to 600 mg/m2/day. These results confirm that zidovudine can safely be used to treat HIV-infected children. The main limitation is serious hematological toxicity which appears to be dose-related. PMID- 8366965 TI - [Cervical myelopathy as complication of manual therapy in a patient with a narrow cervical canal]. AB - A 31-year-old man had manipulative therapy because of pain in the neck, the left shoulder and the left arm. Immediately after cervical traction he developed neurological symptoms. Clinical investigation led to the diagnosis of cervical myelopathy. The patient had a rather narrow cervical canal. Six weeks after treatment with external fixation and corticosteroids the situation had improved markedly, with remaining hypesthesia in both hands and the right leg. PMID- 8366964 TI - [2 children with discitis]. AB - The childhood form of discitis was diagnosed in a 2-year-old girl and a 5-year old boy. They presented with an antalgic posture, muscular defense and a positive Gowers sign. Characteristic symptoms of this childhood discitis form the triad: unexplained fever, increased erythrocyte sedimentation rate and symptomatic narrowing of an intervertebral space. PMID- 8366966 TI - [Storm during the dog days; observations with an article by Dr. W. Storm van Leeuwen from 1932]. AB - In 1932 Storm van Leeuwen, professor of pharmacology in Leiden, together with De Lind van Wijngaarden published data on an increase of common colds in the population in general and an increase of symptoms in asthmatic patients during the period August 8-10, 1931. In asthmatics treated in 'climatized rooms' this aggravation was not observed. In this connection the authors refer to the 'allergen-free' nature of these rooms. After studying the meteorological data of August 1931, however, we conclude that the colds and the aggravation of the asthmatic complaints in the period of August 8-10 were probably due to a sudden fall of the temperature from 30 to 15 degrees C in the period August 5-10, owing to a change of weather with influx of cold polar air. PMID- 8366967 TI - [Antibiotic prophylaxis in closed fractures is cost-effective if the possibility of a deep infection decreases with 0.25%]. PMID- 8366968 TI - [Antibiotic prophylaxis in closed fractures cost-effective when the possibility of a deep infection decreases by 0.25%]. PMID- 8366969 TI - [Turning grey overnight, is it possible?]. PMID- 8366970 TI - [Psychological structure as a guiding principle in forensic practice]. PMID- 8366971 TI - [Blood circulation and energy metabolism of the brain in healthy sleep]. AB - Studies on sleep-related changes of cerebral blood flow (CBF) and cerebral metabolic rate (CMR) provide important information about sleep as an active neurophysiological process. Decreases in global values of CBF and CMR during non rapid-eye-movement sleep illustrate rate role of this sleep period as a quiescent phase for the human brain. Increases in CBF and CMR and fast alterations in cerebral perfusion during rapid-eye-movement sleep are indicative of an active state with labile regulation. Local changes in CBF and CMR characterize the heterogeneity of the underlying physiological regulation. The dynamic feature of cerebral perfusion in relation to electroencephalographic patterns obtained by new recording techniques reflects quantitative uncoupling between cerebral electrical activity and cerebral perfusion during parts of the sleep period. A critical analysis of the current literature and history of sleep research on this topic is presented. PMID- 8366972 TI - [Initial experiences with implantable pump systems for intrathecal therapy of chronic pain conditions]. AB - The therapeutic concept of local administration of opioids into the perimedullar and cerebrospinal fluid is the result of fundamental studies concerning the discovery and localization of specific binding sites. These studies provoked considerable clinical interest, because they suggested a non-destructive and fully reversible method. In our department we have been gathering experience with an implantable pump system for various indications of chronic pain on a sample of 25 patients. The first implantation was performed in February 1987 and the latest included in this study in February 1991. The sample of patients consisted of two groups: (A) Chronic non-malignant pain (13 cases), (B) Chronic pain due to cancer (12 cases). We used two different pump devices: the gas-filled continuous infusion pump (Infusaid, Mod. 400) in 10 cases and the manually tractable micro pump (Cordis) in 15 cases. In 23 cases we decided in favour of an intraventricular drug administration, mainly because of the site of the pain; in each of these a ventricular catheter was placed in the frontal horn of the lateral ventricle. In the remaining two cases, the catheter was placed intraspinally, the catheter tip terminating at thoracic segments. Nine of the patients with cancer-related pain experienced from excellent to acceptable pain relief, as did also 10 patients with chronic non-malignant pain. Side effects were rare. Our findings also indicate that, in carefully selected patients, both malignant and non-malignant pain may be managed satisfactorily with this technique. PMID- 8366973 TI - [Aggressive episodes without amnesia. Differential diagnostic problems based on a case report]. AB - A 21-year-old patient suffered from recurrent attacks characterized by aggression and a varying disturbance of consciousness. He had no amnesia for these episodes. Loss of activity and social withdrawal had heralded the manifestation of the disease. He had delusions at times. The problems of differential diagnosis: schizophrenic disorder, frontal lobe epilepsy, or psychogenic seizures are discussed. PMID- 8366974 TI - [Psychopathologic findings and results of treatment of pension applicants. Comments on the contribution by R. Sandweg, C. Sanger-Alt and G. Rudolf]. PMID- 8366975 TI - Analgesic nephropathy--still a problem? PMID- 8366976 TI - Rate of production of carbon dioxide in patients with a severe degree of metabolic acidosis. PMID- 8366977 TI - Nitric oxide: an inflammatory mediator of glomerular mesangial cells. PMID- 8366978 TI - Dynamics of bone aluminum over one year of functioning renal graft. AB - The concentration of aluminum (Al) in serum, urine, and bone, as well as bone histomorphometry parameters were studied before and 1 year after kidney transplantation (Tx) in 20 dialyzed patients. One year after Tx, serum Al fell significantly from 50.3 +/- 8.8 to 23.9 +/- 2.7 micrograms/l, (53% fall). Bone Al content also decreased significantly from 62.9 +/- 9.0 to 36.5 +/- 7.0 micrograms/kg bone weight, but urine Al excretion was still above normal. The repeat bone histomorphometric examination showed a good recovery of bone resorption which correlated well with serum parathyroid hormone levels, but poorer recovery of indices of bone formation and of the extent of Al deposits in the bone as shown by aluminum staining. PMID- 8366979 TI - Partial purification of a renotropic activity from plasma of uninephrectomized human subjects. AB - A renotropic factor was partially purified by sequential gel filtration and anion exchanger chromatography from plasma of human kidney transplantation donors and a renal cancer patient after uninephrectomy. This activity increased the rate of [3H]thymidine incorporation into DNA in rat cortical tubules, but not in rat liver cells, within the range of 100-200 ng/ml protein. The renotropic activity was detected between 7 and 12 days after uninephrectomy, and at least in 1 case decreased thereafter. This activity was undetected in gel-filtrated plasma of patients after a nonurological surgical procedure. The potency of this renotropic activity and its elution by gel filtration are similar to those displayed by a renal growth factor activity isolated from uninephrectomized rat plasma, as recently reported. PMID- 8366980 TI - Effect of hemodialysis on plasma levels of vasoactive peptides: endothelin, calcitonin gene-related peptide and human atrial natriuretic peptide. AB - To determine the role of vasoactive peptides such as endothelin (ET), calcitonin gene-related peptide (CGRP) and human atrial natriuretic peptide (hANP) in the regulation of blood pressure in uremic patients, and to determine the effect of various types of dialyzer membranes on hemodialysis (HD)-induced changes in plasma levels of such peptides, plasma ET, CGRP and hANP were measured in HD patients and patients on continuous ambulatory peritoneal dialysis (CAPD). Plasma levels of ET, CGRP, and hANP were significantly higher in HD and CAPD patients than in healthy subjects. There were no significant differences in plasma levels of ET, CGRP, and hANP between hypertensive and normotensive HD patients, and no significant correlation was observed between HD-induced changes in plasma levels and changes in blood pressure. Plasma levels of ET decreased when HD was performed using high-flux membranes, such as polyacrylonitrile (PAN), polymethyl methacrylate (PMMA) and cellulose triacetate (CTA), but did not decrease using a saponified cellulose (SC) membrane. Plasma levels of CGRP decreased in the case of PAN, but increased significantly with PMMA and showed no change with SC and CTA. Plasma levels of hANP decreased in all types of dialyzer membranes due to decreased secretion. These results indicate that the effect of HD on plasma levels of ET and CGRP, but not hANP, depends on the type of dialyzer membrane used. PMID- 8366982 TI - Pattern of hyperlipoproteinemia in human nephrotic syndrome: influence of renal failure and diabetes mellitus. AB - Forty-two patients with the nephrotic syndrome were grouped according to the absence or presence of renal failure and/or diabetes mellitus. All patients had a similar degree of hypoalbuminemia and urinary protein losses. A lipid and apoprotein pattern was generated in serum and ultracentrifugally isolated lipoproteins. Low-density lipoprotein composition was essentially normal in uremic patients while in the other patients with the nephrotic syndrome, a considerable lipid enrichment was noted. The very-low-density lipoprotein content in lipids was uniformly increased in nephrotic patients irrespective of the presence of complications. High-density lipoprotein cholesterol and serum apolipoprotein A I and E concentration was significantly reduced in uremic patients with respect to normal subjects and to the other groups considered. Serum apolipoprotein A II and B levels were also decreased in uremics. All patients had increased serum apoprotein C II and C III concentration. We conclude that diabetes mellitus does not affect the pattern of hyperlipoproteinemia of nephrotic syndrome while the characteristic lipoprotein and apoprotein pattern of uremia is present irrespective of nephrosis in uremic, nondiabetic patients. PMID- 8366981 TI - Lipoprotein (a) levels in end-stage renal failure and renal transplantation. AB - Some previous studies have documented an increase in lipoprotein (a) [Lp(a)] levels in renal diseases. Here, we report data in subjects with end-stage renal failure treated with hemodialysis (HD) or with continuous ambulatory peritoneal dialysis (CAPD) and in renal transplant recipients (RTR), compared with a group of normolipidemic controls (C). Lp(a) levels were significantly increased in HD and CAPD patients in comparison with C, while they were only slightly increased in RTR. Both HD and CAPD patients showed Lp(a) levels higher than in RTR, but no difference was found between the subjects of the two dialysis procedures. The prevalence of Lp(a) levels > 25 mg/dl was significantly higher in HD and CAPD patients, but not in RTR, in comparison with C. Moreover, Lp(a) levels did not change after HD. When patients were divided according to their fasting lipid levels in normolipidemics and hyperlipoproteinemics, no difference was found for Lp(a) levels in any group. Mechanisms underlying the increase in Lp(a) levels in these patients are not known. It is possible to suggest an active role of the kidney in the Lp(a) metabolism or that uremic plasma contains some factors affecting Lp(a) metabolism. PMID- 8366983 TI - Salt wastage, plasma volume contraction and hypokalemic paralysis in self-induced water intoxication. AB - Eleven episodes of severe hyponatremia secondary to hiccup-induced potomania were recorded in 3 years in a man who had essential hypertension, a low protein intake and a normal diluting ability. Paradoxical increase in hematocrit and plasma protein with acute extensive natriuresis was associated as well as urine potassium loss and hypokalemia producing paralysis in 1 episode. During a chronic water loading test, the defect in water excretion was related to a low urine solute delivery which was partially reverted by the natriuretic response to plasma volume expansion, promoting water diuresis. In acute water intoxication, this natriuretic response was exaggerated, producing a brisk water diuresis. Plasma volume was rapidly normalized but without any improvement in plasma sodium due to the concomitant negative sodium balance. Thus, water diuresis persisted until plasma volume was significantly contracted. Potassium loss appeared to be related to sodium excretion. Metabolic disturbances have not reoccurred despite persistent hiccup and potomania during 2 years of urea therapy. PMID- 8366984 TI - Effects of hemodialysis on body surface maps in patients with chronic renal failure. AB - To examine the effects of hemodialysis on the electrocardiogram, 87-lead body surface maps were performed in 38 patients with chronic renal failure, before and after hemodialysis. The patients were divided into two groups; 16 patients with coronary artery disease (CAD group), and 22 patients without ischemic heart disease (control group). Three maps were analyzed, QRS isopotential maps, isochrone maps, and QRS isointegral maps. Parameters measured were maximal R wave voltage (Peak R), minimal QRS wave voltage (Peak S), maximal ventricular activation time (VATmax) and QRS duration (QRSd). In the control group, Peak R and Peak S increased but VATmax decreased after hemodialysis. There were negative correlations between the changes of body weight and the changes in Peak R (r = 0.67, p < 0.01) and Peak S (r = -0.87, p < 0.001), although there were no correlations between changes in left ventricular diastolic dimension and the changes in Peak R and Peak S. In the CAD group, Peak S increased but Peak R and VATmax did not change significantly. There were negative correlations between the change of body weight and the change of Peak S (r = -0.73, p < 0.01). The most pronounced changes in mean QRS isointegral maps on hemodialysis were an increased magnitude of positivity in the control group and negativity in the CAD group on the anterior thorax. These findings suggested that the increase in the QRS amplitude after hemodialysis was influenced by the changes of the conductivity of extracardiac thorax and the relative heart position to the chest wall rather than myocardial ischemia or ventricular conduction delay. PMID- 8366985 TI - Dipsogenic effect of urea in rats. AB - Anephric rats injected subcutaneously with urea in isotonic saline drank much more than anephric control animals receiving isotonic saline alone. The pattern of water intake and urine output of normal rats, repeatedly injected with urea solution, was similar to that of rats injected with dipsogenic hypertonic NaCl and quite different from that of rats receiving furosemide. A well-evident dipsogenic effect (unrelated to the urine output) was observed in normal rats repeatedly injected with urea solution and having a rapid rise of serum urea concentrations. On the contrary, in rats receiving a single load of urea and showing first a very rapid increase, then followed by a slow decrease of serum urea concentrations, the dipsogenic effect was present only initially. These results demonstrate that urea exerts a direct dipsogenic action which may be interpreted as a consequence of an osmotic gradient between the extra- and the intracellular fluid. When this is positive, as in the case of a rapid rise of serum urea levels, cell dehydration ensues and thirst is stimulated. On the contrary, when serum urea levels are decreasing and, presumably, when the intra- and the extracellular concentrations of urea are in equilibrium, no cellular dehydration occurs and thirst does not appear. PMID- 8366986 TI - Effect of parathyroid-hormone-related protein on sodium-dependent phosphate transport in renal brush border membrane vesicles in rats. Comparison with parathyroid hormone. AB - Parathyroid-hormone-related protein (PTHrP) has significant homology with parathyroid hormone (PTH) in the amino-terminal region. We compared the effects of synthetic human PTHrP [hPTHrP(1-34)] on Na(+)-dependent phosphate transport with those of synthetic human PTH [hPTH(1-34)]. Intravenous administration of hPTHrP(1-34) in parathyroidectomized rats caused hypercalcemia, hypophosphatemia and phosphaturia to the same degree as hPTH(1-34). In kinetic studies using renal brush border membrane vesicles, the apparent Km and Vmax of phosphate transport were identical for the two peptides [hPTHrP(1-34): Km 27.6 +/- 0.8 microM, Vmax 3.78 +/- 0.04 nmol/mg protein, hPTH(1-34): Km 29.6 +/- 0.9 microM, Vmax 3.04 +/- 0.90 nmol/mg protein]. Both hPTHrP(1-34) and hPTH(1-34) at a supramaximal dose were equipotent in eliciting a 12-fold increase in cyclic adenosine 3',5' monophosphate (cAMP) production in the kidney. These results indicate that, in addition to the similar effect of hPTHrP(1-34) and hPTH(1-34) on serum calcium levels and urinary phosphorus and nephrogenous cAMP excretion in vivo, these two peptides have similar effects of Na(+)-dependent phosphate transport in brush border membrane vesicles in vitro. PMID- 8366987 TI - Changes of adenosine levels in the carotid artery, renal vein and inferior vena cava after glycerol or mercury injection in the rat. AB - The adenosine A1 receptor antagonist (FR113453) prevents glycerol- but not mercury-induced acute renal failure. To clarify this mechanism, adenosine concentration in the renal vein was measured serially. Plasma adenosine in the renal vein increased from the preinjection value of 120.6 +/- 15.4 (mean +/- SEM) pmol/ml to 426.9 +/- 107.5, 407.0 +/- 70.1 and 283.9 +/- 22.9 pmol/ml at 1, 5 and 60 min after intramuscular injection of 10 mg/kg of 50% glycerol into Sprague Dawley rats. On the other hand, intramuscular vehicle (0.9% NaCl) injection and subcutaneous administration of 10 mg/kg of HgCl2 did not change or caused mild elevation of adenosine concentration in the renal vein. Furthermore, simultaneous blood collection from the carotid artery, renal vein and inferior vena cava revealed a greater increase in adenosine concentration in the inferior vena cava than in the artery or renal vein. These findings were not affected by the administration of FR113453 or vehicle (methylcellulose). The increase in adenosine in the inferior vena cava was derived from the release from the acutely damaged muscles due to glycerol injection. These findings suggest that the effect of adenosine A1 antagonist to prevent glycerol-induced acute renal failure is due to the inhibition of adenosine A1 receptor in the kidneys during the release of adenosine through the inferior vena cava. Therefore, the release of adenosine from the muscle and hemolysis plays an important role to induce acute renal failure in the glycerol-injected rat. PMID- 8366988 TI - Effects of endothelin and angiotensin II on renal hemodynamics in experimental mesangial proliferative nephritis. AB - The renal hemodynamic response to pressor substances in the diseased kidney has been suggested to be different from that in the normal kidney. The aim of this study was to investigate the effects of endothelin and angiotensin II on renal hemodynamics in experimental nephritis induced by the administration of antithymocyte serum in Wistar rats. This model showed mesangiolytic lesions in the glomeruli on day 2 and hypercellular lesions on day 8. Prior to the injection of either endothelin or angiotensin II, the glomerular filtration rate and renal plasma flow were significantly lower in model rats on day 2 or day 8 than in the control rats. The basal glomerular filtration rate and renal plasma flow on day 8 were negatively correlated with the mesangium cell number. The injection of endothelin (0.5 ng/kg BW) led to a decrease in both renal plasma flow and glomerular filtration rate in rats on day 8 which was significantly greater than that in the control rats. Similarly, angiotensin II infusion (0.2 micrograms/kg BW) reduced both renal plasma flow and glomerular filtration rate in the rats on day 8 and the reductions were significantly greater than those in the control rats. In conclusion, renal hemodynamics in rats with mesangial proliferation of the kidney were more sensitive to both endothelin and angiotensin II than those in the normal kidney. PMID- 8366989 TI - Compensatory renal hypertrophy: tubular cell growth and transport studied in primary culture. AB - In order to define the growth and transport characteristics of renal epithelia during hypertrophy, primary culture of proximal tubular cells was established from kidneys of normal rats and those with compensatory renal hypertrophy (CRH) induced by unilateral nephrectomy. At confluence, enhanced growth potential was preserved in the cells derived from the animals with CRH (CRH cells) as compared with cells derived from normal animals (N cells), as evidenced by an increased cellular protein content (250 +/- 12 vs. 151 +/- 11 pg protein/cell; p < 0.001) and a somewhat lesser increase in cellular thymidine incorporation (6,820 +/- 52 vs. 5,151 +/- 308 cpm/10(6) cells; p < 0.02). The cellular Na transport (measured as 22Na uptake) was increased in the CRH cells, being 733 +/- 47, 886 +/- 111, and 1,026 +/- 147 cpm/1,000 cells at 1, 3, and 120 min, respectively, versus 353 +/- 36, 469 +/- 31, and 549 +/- 41 cpm/1,000 cells in N cells (p < 0.05 for each time point), i.e., an increase in Na transport in CRH cells of 107, 88, and 87%, respectively. Addition of Amiloride inhibited Na uptake in N cells by approximately 50% and completely suppressed the excess Na uptake in CRH cells to values observed in normal animals, i.e, 147 +/- 33, 224 +/- 91, and 174 +/- 86 cpm/1,000 cells in CRH cells at 1, 3, and 120 min respectively, versus 181 +/- 71, 164 +/- 57, and 238 +/- 85 cpm/1,000 cells in N cells (p = NS at each time point).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8366990 TI - Acute renal failure from inhalation of mycotoxins. AB - Mysterious deaths of archeologists after opening Egyptian tombs have been suspected to be secondary to inhalation of mycotoxin, however, the hypothesis has never been verified. Recently, we observed a case of acute renal failure (ARF) undeniably due to inhalation of ochratoxin of Aspergillus ochraceus. After spending 8 h in a granary which had been closed for several months, a farmer and his wife suffered temporary respiratory distress; 24 h later, the woman developed nonoliguric ARF and biopsy revealed tubulonecrosis which healed in 24 days. Toxic substances were not found, but a strain of A. ochraceus producing ochratoxin was isolated from the wheat. PMID- 8366991 TI - Clinical course of late-onset bone marrow transplant nephropathy. AB - Late-onset renal insufficiency is an increasingly recognized complication of bone marrow transplantation (BMT) which occurs between 6 and 12 months after BMT. This syndrome, which has occurred in 25% of our 2-year survivors, is characterized by azotemia, hypertension, and disproportionate anemia. A minority of our subjects have had a presentation similar to hemolytic-uremic syndrome, with rapid decline in kidney function. The others have had slower declines in kidney function, without apparent ongoing hemolysis. Stabilization of function has occurred in about one third of cases. Light microscopy has shown mesangial and endothelial cell dropout with widening of glomerular capillary loops. Electron microscopy has shown a striking subendothelial expansion of the glomerular basement membrane. This syndrome is similar to acute radiation nephritis. Stabilization of kidney function has occurred in some cases, perhaps reflecting control of the blood pressure. Studies of the prevention of this condition are needed because of the frequency of its occurrence and the growing number of BMT worldwide. PMID- 8366992 TI - Prevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus among dialysis patients. The Italian Multicentric Study on Nosocomial and Occupational Risk of Blood-Borne Infections in Dialysis. AB - In April 1991, a cross-sectional study of HIV, HBV and HCV markers among dialysis patients was carried out in 19 Italian units in order to evaluate the spread of these bloodborne infections among patients and to evaluate the potential risk for staff who care for them. A total of 2,180 patients were eligible and all consented to be tested. Of the 1,347 patients who had not been given hepatitis B vaccine, 67.9% had at least one marker of HBV infection; of these 9.2% were HBsAg carriers; conversely, the rates were 7.6 and 0.4%, respectively, among the 833 vaccinated patients. Antibodies against HCV were found in 501 patients (23%) by EIA C100-3; of these, 270 were tested by RIBA-100: 246 (91%) were reactive and 11 (4.1%) indeterminate. Five patients resulted anti-HIV positive [0.22%, 95% CI (Poisson distribution): 0.07-0.53] by EIA and Western blot techniques. Length of time on dialysis seems to correlate with higher prevalence of HBV and HCV infection markers, but (not) HIV. Overall, 608 (28%) patients were a potential source of infections for other patients and staff. This emphasizes the need for stricter adherence to infection control, barrier precautions and preventive behaviours with all patients. PMID- 8366993 TI - Pseudohyponatremia and pseudohyperphosphatemia in a patient with human immunodeficiency virus infection. PMID- 8366994 TI - Pentoxifylline in management of proteinuria in diabetic nephropathy. PMID- 8366995 TI - Antiproteinuric effect of glycosaminoglycans? PMID- 8366996 TI - Resistance to recombinant human erythropoietin in a child with renal failure, cystinosis and beta-thalassaemia minor. PMID- 8366997 TI - Pores in the glomerular basement membrane revealed by ultrahigh-resolution scanning electron microscopy. PMID- 8366998 TI - Unilateral reflux nephropathy with contralateral renal artery stenosis due to fibromuscular hyperplasia. PMID- 8366999 TI - Conflicting results of hepatitis C virus serological tests in haemodialysis patients. PMID- 8367000 TI - Syndrome of tubulointerstitial nephritis and uveitis: is it worth considering it as a proper entity? PMID- 8367001 TI - Anticardiolipin antibodies in patients on regular hemodialysis: an epiphenomenon? PMID- 8367002 TI - [Fibrillary glomerulopathies]. PMID- 8367003 TI - [Renal effects of endothelins]. AB - Since the discovery of endothelin in 1988, numerous studies have been undertaken to evaluate their physiopathologic role. There is three types of endothelin ET-1, ET-2 and ET-3, which probably play an essential role in renal and cardiovascular homeostasis. Their principal actions consist in an increase of the arterial pressure, a negative inotrope and chronotrope effect, a coronary vasoconstriction, a decrease in cardiac output and a fall in the renal blood flow and glomerular filtration rate. An elevation of endothelin level has been reported in numerous clinical conditions. However the interest of these descriptions remains unclear. Indeed the absence of pharmacological inhibitors of the synthesis or effect of endothelin prevent the understanding of the interest of these abnormalities. Furthermore the endothelins should not be considered as a hormone but as a paracrine substance. PMID- 8367004 TI - [Severe hypertension and renal infarct. Physiopathology and treatment. Apropos of 1 case]. AB - Renal infarction can be complicated by arterial hypertension, which is sometimes severe and may present as hypertensive encephalopathy and epilepsy. We report such a case in whom angiographic studies revealed a stenosis of the left renal artery and a post-stenotic aneurysmal dilation, containing a large thrombus with distal embolization. Thrombolysis associated with angioplasty resulted in the disappearance of the thrombus and correction of the stenosis. The pathophysiology of hypertension secondary to renal infarction is discussed. Therapeutic modalities are reviewed. PMID- 8367005 TI - [Peritoneal tuberculosis and continuous ambulatory peritoneal dialysis]. AB - Depressed immunity in uremic patients increases by ten the risk of tuberculosis. In such patients, 40% of tuberculosis manifestations are extrapulmonary, and peritoneum is involved in about 6% of the cases. Seventeen cases of peritoneal tuberculosis have been so far reported in CAPD patients, and we add a new case. The prognosis of the disease is severe since 8 patients died. Three deaths out of 8 are directly linked to tuberculosis. Indeed, peritoneal tuberculosis diagnosis is hard and often late, at least for two main reasons: at first, it can be difficult to exclude the other causes of lymphocytic peritonitis (viral, fungal, bacterial, etc.), secondly, growth of mycobacteria in dialysate effluent cultures is late and inconstant. Omental biopsy in lymphocytic peritonitis of unknown origin could be of great value for an early diagnosis. Despite the adaptation of antituberculous drugs doses, side-effects are not so rare: optical neuritis and liver toxicity in our case. In spite of ultrafiltration loss, stopping CAPD is not always necessary, as in the reported case. PMID- 8367006 TI - [Nephropathies and HIV virus infection. Anatamo-clinical study]. AB - We report 16 patients with HIV1 infection with biopsy-proven renal involvement. Nine patients were caucasians and seven were blacks. There were 11 patients at stage II and 5 at stage IV of the HIV1 infection. Three patterns of histologic lesions were found: 6 patients, all blacks, with nephrotic syndrome and/or renal insufficiency had focal and segmental glomerulosclerosis (FSGS) with tubulo interstitial lesions. In contrast, 6 patients, all caucasians, had various types of glomerulonephritis characterized by immunoglobulin and complement deposits; 3 of them were membranoproliferative glomerulonephritis (MPGN). The four remaining patients had predominant tubulointerstitial lesions. In three patients who had FSGS, treatment by AZT induced temporary improvement of renal function and hemodialysis could be interrupted for a few months. The cure of infectious foci was followed by improvement in renal signs in two out of the 3 MPGN patients. Our study further underlines: 1) the importance of genetic/racial factors in the occurrence of HIV1-associated glomerular lesions and 2) the relatively frequent occurrence of MPGN related to bacterial infections in caucasian patients. PMID- 8367007 TI - [Regional anticoagulation with sodium citrate: chronic utilization in the hemodialysis patient]. AB - We used an alternative technique for regional citrate anticoagulation (citrate 0.48 Mol; bicarbonate containing dialysate with Ca 1.75 Mmol) in three patients at chronic risk of bleeding and for a mean follow-up period of ten months. No bleeding recurrence was observed nor any complication related to citrate. Hemoglobin and hematocrit rose without transfusions. Serum bicarbonate increased during the first four months of treatment. No significant change was observed in serum calcium nor serum sodium concentration. PMID- 8367008 TI - [Severe metabolic alkalosis due to error of dialysis concentration]. PMID- 8367009 TI - New stereological methods for counting neurons. AB - The issue of whether or not neurons die with age is of fundamental importance for understanding senescent decline in motor, sensory, and cognitive functions. Yet after over 100 years of attempts to quantify age-related neuron loss, this fundamental issue is "swirling in controversy" and the results of numerous studies addressing this issue "rife with confusion and seemingly contradictory data" (7). This is in large part due to deficiencies in the way we have thought about what constitutes evidence for neuron loss and deficiencies in the methods that have been available for counting neurons. Over the past several years, a new generation of stereological principles have been developed that have made it possible to identify and eliminate these deficiencies. Although there are now a number of review articles that briefly describe these and other new stereological principles (4,9,13,14,15,18,23), for the most part detailed descriptions of the new principles for counting neurons are found in specialized literature and are accompanied by new terms and concepts that have overwhelmed potential users and inhibited their adoption. In this essay, I describe the principles and concepts that are involved in the new stereological approach to neuron counting and discuss why the data obtained from their application represent improvements over those obtained with previously available techniques. A practical guide to the application of the principles to counting neurons or any other cell, organelle, or object present in sectioned material has been included as an appendix. PMID- 8367010 TI - Regionally specific loss of neurons in the aging human hippocampus. AB - New highly-accurate stereological methods for estimating the total numbers of neurons in brain structures have been used to test for age-related neuron loss in the human hippocampal formation. Across the age range of 13 to 85 years, there was a substantial loss of neurons in the subiculum (52%) and in the hilus of the dentate gyrus (31%); the three remaining hippocampal subdivisions showed no significant change. These losses qualify as potential morphological correlates of senescent decline in relational memory in that they can be expected to compromise the functional integrity of a region of the brain known to be intimately involved in this type of memory. The regional pattern of neuron loss is similar in certain respects to the patterns of cell loss seen during the initial phases of ischemia and epilepsy and is fundamentally different from the pattern associated with Alzheimer's disease. PMID- 8367011 TI - Morphometric image analysis of neuropil threads in Alzheimer's disease. AB - Neuropil threads were quantitated in the neuropil (excluding senile plaques) of the superior frontal gyrus of 6 late stage patients with Alzheimer's disease (AD) and 6 age-matched control subjects using tau immunocytochemistry and computerized morphometric image analysis. The mean percent of the area of the neuropil occupied by neuropil threads was 10.6 for AD and 0.19 for controls (p < 1 x 10( 10)). The mean length of neuropil threads in AD was 21.9 mu compared with 19.7 mu for controls (p < 1 x 10(-10)). The mean area of neuropil threads was 25.3 mu 2 for AD and 21.3 mu 2 for controls (p < 1 x 10(-10)). In AD, the threads were most prominent in mid cortex (lamina 2 and 3) and least prominent in the lower cortex (lamina 5 and 6). Neuropil threads appear to lead to severe disorganization of intracortical and corticocortical connectivity and probably play a role in the cognitive failure in AD. PMID- 8367012 TI - Effects of aging on spatial learning and hippocampal protein kinase C in mice. AB - C57BL/6Nia and F1(B6xD2)Nia mice were tested on the Morris water maze task for 5 days followed by 12 days of testing on the place learning-set task (8 trials/day with each task). Mice were tested at 3, 14, and 25 months of age. C57 mice, 25 months of age, were significantly impaired in both the Morris and place learning set task probe trial performance compared to mice 3 months of age (p < 0.05). These aged C57 mice also demonstrated a significant reduction in membrane-bound hippocampal protein kinase C (PKC) activity (p < 0.05) with no significant change in cytosolic PKC activity. F1 mice, however, showed no effect of age on probe trial performance on the spatial learning tasks. In addition, in a comparison of C57 and F1 mice within each age group, F1 mice demonstrated superior learning performance which was accompanied by a significant elevation in PKC activity (p < 0.05). Spatial learning performance of both strains significantly correlated with membrane-bound PKC activity (p < 0.01). These data provide additional support for our previous hypothesis of an involvement of hippocampal PKC activity in spatial learning and suggest that the amount of membrane-bound PKC activity may be a determinant of age-related decline in spatial learning. PMID- 8367013 TI - Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine. AB - Changes in lipid peroxidation, lipofuscin concentration, and multiple unit activity (MUA recorded in conscious animals) in the CA3 region were studied in the hippocampus of male Wistar rats aged 4, 8, 16, and 24 months. The lipid peroxidation and lipofuscin concentration were increased with age. The MUA, however, declined with age. Correlational analyses were performed for the four age groups to determine the relationship between the age-associated decline in MUA with the age-related alterations in lipid peroxidation and lipofuscin concentrations. The age-related increase in lipid peroxidation correlated positively with the age-associated increase in lipofuscin concentration. The age related increases in lipid peroxidation and lipofuscin concentration correlated negatively with the changes in MUA. Since lipid peroxidation may affect neuronal electrophysiology, our data suggested that age-related increase in lipid peroxidation may contribute to an age-associated decline in neuronal electrical activity. Centrophenoxine effects were studied on the three above-mentioned age associated changes in the hippocampus. The drug had no effect on all three parameters in 4- and 8-month-old rats. In 16- and 24-month-old rats, however, the drug significantly increased the MUA but concomitantly decreased lipofuscin concentration and lipid peroxidation. Correlational analyses of the data on MUA, lipid peroxidation and lipofuscin concentration from the centrophenoxine-treated animals showed that the drug-induced diminution in both lipofuscin and lipid peroxidation was significantly correlated with the drug-induced increase in MUA. The differential effect of the drug in younger (4-8 months) and older (16-24 months) animals indicated that the stimulation of MUA was clearly associated with concomitant decrease in lipid peroxidation and lipofuscin concentration. PMID- 8367014 TI - Effect of exercise on age-related muscle atrophy. AB - Fifty-five-week-old male Wistar rats exercised voluntarily in running wheels for 10 weeks. The number and cross-sectional area of fibers in the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles were recorded and compared with those of 20-week-old rats, and of age-matched rats not exercised. Muscle fibers were classified as fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), or slow-twitch oxidative (SO). After injection of horseradish peroxidase into the SOL and TA for retrograde neuronal labeling, oxidative enzyme activity of labeled motoneurons in the spinal cord was measured by microspectrophotometry. There were fewer FOG fibers in the SOL, and fewer FG fibers in the TA, at 65 weeks than at 20 weeks of age. The cross-sectional area of FOG and FG fibers in the TA was lower at 65 weeks than at 20 weeks of age. Exercise prevented the atrophy of FOG fibers in the TA. There were no age- or exercise-related differences in the number or oxidative enzyme activity of motoneurons in the SOL or the TA. These findings suggest that exercise can prevent the atrophy of FOG fibers by restoring their decreased metabolic capacity, and by inhibiting the degeneration of neuromuscular junctions. PMID- 8367016 TI - Axonal loss from the olfactory tracts in Alzheimer's disease. AB - Senile dementia of the Alzheimer type has been shown to be associated with impaired olfactory function early in the course of the disease. Neuropathology in the olfactory system is also a feature of Alzheimer's disease (AD) and it has been suggested that the disease may be caused by a pathogen entering the brain via olfactory pathways. To investigate this hypothesis, the effect of AD on the olfactory tract was investigated. There was a 40% decrease in the cross-sectional area of the olfactory tract and a 52% loss of myelinated axons from the tract in AD. These results, together with those of previous studies suggest that peripheral regions of the olfactory system, i.e., the olfactory bulb and primary sensory olfactory neurons are less affected by the pathology of AD than more central parts, i.e., cortical regions, the anterior olfactory nuclei, and olfactory tract. This less severe pathology at the periphery argues against a pathogen entering the brain via the peripheral olfactory apparatus and suggests a central pathogenesis which spreads centrifugally along olfactory pathways. PMID- 8367015 TI - Neuronal hypertrophy in the hypothalamus of older men. AB - A striking neuronal hypertrophy occurs in the infundibular nucleus of postmenopausal women. To determine the gender specificity of this response, we measured the areas of neuronal profiles in the infundibular nucleus of young (21, 32, and 41 years) and older (60, 61, and 68 years) men and compared them to data reported previously from the hypothalami of pre-(28, 32, and 40 years) and postmenopausal women (58, 62, and 74 years). Sagittal blocks of formalin-fixed hypothalami were paraffin embedded, serially sectioned and stained with cresyl violet. The profile areas of 2,429 infundibular neurons were manually digitized using an image-combining computer microscope. The contralateral hypothalamus of each subject was cryoprotected, frozen-sectioned in the coronal plane and also stained with cresyl violet. The infundibular nuclear volume and the total number of neurons were estimated from the coronal sections using stereological methods. The mean profile area of infundibular neurons from older men (176.6 +/- 1.7 microns 2) was significantly larger than that of young men (147.0 +/- 1.3 microns 2). There was also a significant increase in the density of hypertrophied neurons (> 226 microns 2 profile area) in the infundibular nucleus of older men. There was no difference in infundibular nucleus associated with an average neurons was significantly increased in the older men. A comparison with previous data obtained from pre- and postmenopausal women revealed that the profile area of infundibular neurons was equal in young men and young women. However, the profile area of neurons in the postmenopausal women (190.4 +/- 2.1 microns 2) was significantly greater than that of older men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367017 TI - Effect of repeated stress on plasma catecholamines and taurine in young and old rats. AB - The effect of age and multiple stress responses on plasma norepinephrine (NE), epinephrine (EPI), and taurine (TAU) levels were determined in F344 rats. Blood samples obtained from catheterized young (3 months) and old (24 months) animals were used to examine plasma levels of NE, EPI, and TAU under baseline conditions and in the same animals after a 30-min immobilization stress. Rats were again immobilized and blood drawn (Day 3) following a 1-day rest period and, after an additional 4-day rest period (Day 7). Age differences seen between young and old rats were not the same for the three neurochemicals measured but were relatively unique for the specific biochemicals. In old animals baseline values of NE but not EPI and TAU were higher then young animals and all three values did not change for the baseline during the two additional stress exposures. Initial stress responses were similar for all three biochemicals in both age groups. Although no signs of adaptation were evident in the old animals, adaptation to immobilization was seen for EPI and TAU but not NE on the third occasion in the young animals. Correlations seen between NE and EPI in young and old rats on the first day disappeared during the second stress period but were again seen during the third stress exposure suggesting subtle indicators of repeated stress subject to adaptation. TAU values for young but not old rats correlated positively with EPI concentrations during the first stress exposure and negatively after the immobilization was terminated indicating a regulatory interaction between EPI and TAU present in young but lost in old animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367018 TI - Inhibition of cytosolic human forebrain choline acetyltransferase activity by phospho-L-serine: a phosphomonoester that accumulates during early stages of Alzheimer's disease. AB - There is no satisfactory explanation for the cholinergic deficit characteristic of Alzheimer's disease. We have performed a series of experiments which demonstrate that (a) an inhibitor of cytosolic human brain choline acetyltransferase is present in the cytosol of Alzheimer brain tissue, (b) human brain cytosolic choline acetyltransferase activity is inhibited by phospho-L serine in a competitive manner. Cytosol was prepared from human forebrain or amygdala and the Km for choline and acetyl CoA of the choline acetyltransferase were 750 microM and 12.5 microM, respectively. Phospho-L-serine was found to be a competitive inhibitor of this enzyme with respect to choline but not with respect to acetyl CoA with a Ki of 750 microM for the human forebrain and 3 mM for human amygdala. These concentrations of phospho-L-serine are present in brain tissue at early stages of Alzheimer's disease. Several other phosphomonoesters and phosphodiesters that are increased in Alzheimer's disease were either less inhibitory or without effect. The addition of heat denatured and non-heat denatured cytosol from Alzheimers forebrain inhibited the choline acetyltransferase activity present in control human brain cytosol. The inhibitory activity of the Alzheimers cytosol was retained in TCA deproteinized samples and removed by dialysis or by alkaline phosphatase treatment. Dialysis of the cytosol increased the choline acetyltransferase activity of 5 of 8 Alzheimer's disease samples from 21 to 118% with p values of < 0.025 or < 0.001, respectively. These observations provide evidence that an endogenous non-proteinaceous, dialyzable, phosphomonoester, present in Alzheimers brain inhibits the choline acetyltransferase of both control and Alzheimers brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367019 TI - Analysis of Na+/Ca2+ exchange activity in human brain: the effect of normal aging. AB - Na+/Ca2+ exchange activity and passive permeability to Ca2+ were analyzed in plasma membrane vesicles (PMV) purified from whole rat brain and three regions of human brain: frontal cortex, temporal cortex, and cerebellum. Accumulation of Ca2+ due to Na+/Ca2+ exchange activity showed a characteristic pattern of an initial rapid rise in Ca2+ content followed by a stable plateau in both rat and human brain. Total Ca2+ accumulation in rat brain PMV was on average three-fold higher than in human brain. Passive permeability to Ca2+ was measured as the rate of Ca2+ release from PMV first loaded with 45Ca by Na+/Ca2+ exchange and then exposed to 1 mM EGTA. The Ca2+ permeabilities of human and rat brain PMV were similar. Ca2+ release from rat brain PMV was faster overall and was resolved into fast and slow components while in human brain a single slow component was found. Post mortem delay up to 4 h had no effect on Na+/Ca2+ exchange Km for Ca2+, Vmax, and peak uptake and Ca2+ release rate in rat brain PMV. Human frontal cortex was shown to have a greater Na+/Ca2+ exchange activity than that found in the cerebellum. The frontal cortex, temporal cortex and cerebellum had similar Ca2+ permeabilities. Age-related effects on Na+/Ca2+ exchange activity and Ca2+ permeability were determined in 15 tissues from human frontal cortex (age at death 21 to 93 years). No significant age related effects were seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367020 TI - 3-D reconstruction of the cholinergic basal forebrain system in young and aged rats. AB - The 3-dimensional (3-D) distribution of cholinergic neurons located throughout the extent of the entire basal forebrain of young (4-5 months old) and aged (24 25 months old) Fischer-344 rats was examined using choline acetyltransferase immunocytochemistry (ChAT-IR). The number and 3-D position of ChAT-IR neurons spanning the basal forebrain were determined using serial sections and analyzed using computerized image analysis. The effects of aging on ChAT-IR neuron number were analyzed as a cohesive unit with respect to the classically-defined magnocellular subregions located within the basal forebrain (i.e., the medial septum, vertical and horizontal limbs of the diagonal band, and the nucleus basalis). Significant effects of age were found on ChAT-IR neuron number but no significant age-related interactions were noted with either the A-P, M-L, or D-V axes. These results suggest that a significant but diffuse age-related loss of ChAT-IR occurs along the entire length of the basal forebrain, and that this loss is not restricted to individual magnocellular nuclei (A-P axis), the M-L axis, or the D-V axis. PMID- 8367021 TI - Chronic methanesulfonyl fluoride enhances one-trial per day reward learning in aged rats. AB - Aged (24-month-old) rats were treated chronically with methanesulfonyl fluoride (MSF), an acetylcholinesterase (AChE) inhibitor with selectivity for central nervous system AChE, or with injection vehicle alone. Twelve 0.22 mg/kg IP injections were given over 4 weeks. MSF rats showed significantly greater speed and accuracy on a 1 trial/day discriminative reward learning task. The chronic MSF treatment resulted in a 56% decrease in brain AChE activity but no discernable locomotor side effects and no liver damage as indicated by aspartate transferase activity. PMID- 8367022 TI - Cold-induced increases in phenylethanolamine N-methyltransferase (PNMT) mRNA are mediated by non-cholinergic mechanisms in the rat adrenal gland. AB - Previously, we reported that cold stress induces a rapid increase in adrenomedullary PNMT mRNA levels, followed by concomitant increases in PNMT immunoreactivity (10). In the present study, the extracellular signals mediating this adaptive response to stress were investigated using northern analysis and RNA slot-blot hybridization. Although adrenal denervation significantly diminished cold-induced increments in adrenomedullary PNMT mRNA levels, it did not completely abolish the cold stress response. In contrast to these results, splanchnectomy completely inhibited cold-induced increments in TH mRNAs in the same tissue samples. These findings indicate that the effects of cold exposure on PNMT mRNA levels are mediated by both neural and non-neural mechanisms, and that adrenal PNMT and TH are differentially regulated in response to cold stress. Surprisingly, the neural component of the PNMT stress response could not be attenuated by peripheral administration of chlorisondamine, a powerful nicotinic ganglionic blocking agent. In contrast, chlorisondamine was effective in inhibiting sympathetic neural activity, as judged by the drug's ability to completely block increases in blood pressure, heart rate, and plasma catecholamines resulting from spinal cord stimulation in pithed rats. The administration of atropine, a muscarinic receptor antagonist, also failed to inhibit cold-induced alterations in adrenal PNMT mRNA. These results suggest that the trans-synaptic induction of adrenal PNMT mRNA involves a non-cholinergic component, and that cold-induced increases in PNMT mRNA are not coupled to acetylcholine-mediated adrenal catecholamine release. PMID- 8367023 TI - Sulfation of hypertensive and hypotensive drugs by monkey brain phenol sulfotransferase. AB - The substrate specificity and affinity of two forms of phenol sulfotransferase (PST) from Rhesus macaque brain cortex were studied. Catecholamines, their methylated metabolites (normetanephrine, metanephrine) and methylated precursor, alpha-methylDOPA, were examined as substrates for both the cationic (PST I) and the anionic (PST II) forms of the enzyme. Sulfation of hypertensive drugs (phenylephrine, octopamine, metaraminol), hypotensive drugs (alpha-methylDOPA, minoxidil), and related agents without a free hydroxy group on the benzene ring were also studied. Results indicated that both PST forms sulfated alpha methylDOPA and minoxidil, but only PST II transferred the sulfate group to catecholamines and most of the adrenergic agents examined. PMID- 8367025 TI - Hippocampal input to the hypothalamus inhibits thyrotrophin and thyrotrophin releasing hormone gene expression. AB - We have used in situ hybridization histochemistry to determine the effect of hippocampal-hypothalamic disconnection on hypothalamic thyrotrophin-releasing hormone (TRH) and anterior pituitary thyrotrophin beta subunit (TSH beta) transcripts in adult male CFY rats. Electrothermal lesions of the fornix pathway significantly increased TRH and TSH transcripts and increased circulating levels of triiodothyronine (T3). Fornix transection did not, however, prevent feedback regulation of TRH and TSH transcripts during exogenous T3-induced hyperthyroidism or propylthiouracil-induced hypothyroidism. Hippocampal inputs to the hypothalamus contribute to setting the basal activity of the thyroid axis, but do not mediate the feedback effects of T3. PMID- 8367024 TI - Evidence that the major physiological role of TRH in the hypothalamic paraventricular nuclei may be to regulate the set-point for thyroid hormone negative feedback on the pituitary thyrotroph. AB - If a primary physiologic action of TRH is to regulate the set-point for negative feedback, a sudden drop in plasma thyroid hormone concentration should stimulate the same rate of in vivo increase in TSH secretion from normal and TRH-deprived thyrotrophs. To test this hypothesis, 3 experiments were performed in which young adult female rats were divided into 3 groups of 6-10 rats each: intact controls, hypothalamic paraventricular nuclei ablation (PVN) and sham-ablated (Sham). Sham and PVN rats were thyroparathyroidectomized 2-4 weeks after brain lesions and serial blood samples taken in all groups at frequent intervals from 0 to 58 days post-thyroidectomy. Plasma TSH was significantly higher than in intact controls by 3 days post-thyroidectomy in both the Sham and PVN groups (p < 0.05). At 14 days PVN plasma TSH was 4 x higher and at 30 days 8 x higher than in intact controls and remained consistently at 50% of that of the Sham group. There was no statistical difference between PVN and Sham in the rate of increase in TSH. Plasma T4 was 40% lower in PVN than in Sham at the time of thyroidectomy and became undetectable in both by day 3. The prompt parallel rate of rise of plasma TSH in Sham and PVN groups following thyroidectomy indicates that a primary physiologic action of TRH in the thyrotroph is to control the set-point for thyroid hormone negative feedback on TSH secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367026 TI - Increases in neuropeptide Y content and gene expression in the hypothalamus of rats treated with dexamethasone are prevented by insulin. AB - The neurotransmitter neuropeptide Y (NPY) is abundant in the hypothalamus where its actions include the potent stimulation of food intake. The peripheral metabolic and hormonal signals involved in its regulation are not clear. The aim of this study was to investigate possible actions of corticosteroids and insulin on hypothalamic NPY synthesis and content in vivo. We measured NPY content in individual hypothalamic nuclei, and hypothalamic NPY mRNA by Northern blotting in whole hypothalamus in rats treated with dexamethasone (0.4 mg/kg/day) and dexamethasone plus insulin (60 U/kg/day), compared to controls. The effect of stopping dexamethasone treatment was also studied. Dexamethasone treatment produced significant increases in NPY in the paraventricular (11.0 +/- 1.3 vs. 7.1 +/- 0.4 fmol/micrograms protein, p < 0.05) and arcuate (6.2 +/- 0.3 vs. 3.8 +/- 0.2 fmol/microgram protein, p < 0.001) nuclei of the hypothalamus, paralleled by a 38% increase in total hypothalamic NPY mRNA (p < 0.05). These changes were not seen in the group treated with dexamethasone plus insulin. In the group in whom dexamethasone was stopped, NPY mRNA was unchanged compared to controls, but peptide content remained increased in the arcuate but not the paraventricular nucleus (arcuate 7.7 +/- 0.7 vs. 5.5 +/- 0.7, PVN 4.9 +/- 1.0 vs. 4.7 +/- 0.9 fmol/microgram protein). Thus hypothalamic NPY and its mRNA were increased by corticosteroid administration, and this effect was prevented by systemic insulin treatment. This dual regulatory system for hypothalamic NPY may be important in the control of food intake by corticosteroids and insulin. PMID- 8367027 TI - Ovarian control of gonadotropin hormone-releasing hormone pulse generator activity in the rhesus monkey: duration of the associated hypothalamic signal. AB - The activity of the GnRH pulse generator in the rhesus monkey is associated with abrupt increases in multiunit electrical activity (MUA) volleys recorded from the mediobasal hypothalamus that precede each pulse of LH in the peripheral circulation. In long-term ovariectomized animals the duration of these MUA volleys is 10-25 min and consists of a brief initial 'overshoot' followed by a plateau phase that ends in a rapid decline to baseline activity. In intact monkeys, however, the MUA volley lasts only 1-3 min, a duration equivalent to the overshoot in ovariectomized animals. In addition, the maximal frequency of neuronal activity during each MUA volley is reduced in normal animals when compared to castrates. As shown in earlier studies, estradiol given to ovariectomized monkeys causes a reduction in the duration of MUA volleys to that characteristic of intact animals within 3-5 h. In contrast to this acute effect of estradiol, the increase in MUA volley duration following ovariectomy is a gradual phenomenon, 4-6 weeks being required to achieve the MUA volley duration observed in long-term ovariectomized monkeys. A similar slow time course was observed for the increase in maximal neuronal frequency during each MUA volley. This protracted effect of ovariectomy on MUA volley duration and firing rate may be the consequence of hypothalamic remodelling but this consideration must be tempered by the observation that estradiol reverses these phenomena within hours. PMID- 8367028 TI - Increased vasopressin secretion and release in mice transgenic for the rat arginine vasopressin gene. AB - The rat arginine vasopressin (AVP) genomic sequence has been utilized to develop a line of transgenic mice homozygous and heterozygous for the transgene. Expression of the rat AVP gene was demonstrated by Southern blotting and resulted in increased amounts of AVP in hypothalamus and frontotemporal brain cortex. Secretion of AVP from the neurohypophysial system results in an increased concentration of the hormone in the plasma and in an increased excretion in the urine in amounts three to five times those of normal mice. Extraneural ectopic hormone production was found only in the pancreas. Despite chronic hypersecretion of AVP, 24-hour urine volume and osmolality did not show evidence of increased antidiuretic hormone action on the kidney, so that, under basal conditions, the water balance in the animals is unaffected. PMID- 8367029 TI - Effects of single or repeated immobilization on release of norepinephrine and its metabolites in the central nucleus of the amygdala in conscious rats. AB - The release of norepinephrine (NE) and its metabolites in the central nucleus of the amygdala was measured using in vivo microdialysis during immobilization (IMMO) stress in conscious rats. Animals underwent 2-hour periods of IMMO either once or daily for 7 days. Extracellular fluid concentrations of NE, dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), and the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were measured before, during, and after IMMO. Microdialysate levels of NE and DHPG attained 2- to 3-fold increments during the 1 h of IMMO and declined thereafter, whereas MHPG and DOPAC levels attained maximal levels of about twice basal concentrations during the 2- or 3-h after initiation of IMMO. After the sixth IMMO basal levels of NE, DHPG, MHPG, and DOPAC were decreased, and NE, DHPG, and DOPAC responses during the seventh IMMO failed to attain levels found during the first IMMO, although the absolute changes during IMMO were similar between animals subjected to IMMO once or seven times. The results indicate that acute IMMO increases synthesis, release, and metabolism of NE in the central nucleus of the amygdala and that repetition of IMMO decreases basal catecholamine synthesis and noradrenergic turnover in this brain region, without inhibiting acute noradrenergic responses. PMID- 8367030 TI - Opioid peptidergic control of gonadotropin-releasing hormone pulse generator activity in the ovariectomized goat. AB - The role of endogenous opioid peptides in the control of gonadotropin-releasing hormone pulse generator activity was examined in long-term ovariectomized goats by recording the hypothalamic multiple-unit activity specifically associated with pulsatile luteinizing hormone secretion (MUA volleys). Administration of naloxone, an opioid receptor antagonist, at a rate of 1.0 mg/kg/h for 2 h resulted in shorter (p < 0.05) intervals between MUA volleys than during the control period (61.6 +/- 0.7 vs. 92.5 +/- 7.2 min) in animals treated with progesterone and estradiol that had reproduced a steroidal milieu during the luteal phase. Similarly, in the absence of steroidal treatment, the interval between MUA volleys was shortened (p < 0.01) in a dose-dependent manner from 42.3 +/- 3.7 min (control) to 35.1 +/- 3.9, 32.6 +/- 4.1, and 27.0 +/- 1.7 min when infused with 0.2, 1.0, and 5.0 mg/kg/h of naloxone, respectively. On the other hand, the duration of each MUA volley was lengthened by naloxone. The results indicate that the hypothalamic gonadotropin-releasing hormone pulse generator activity is under a tonic suppression by endogenous opioid peptides in ovariectomized goats. PMID- 8367031 TI - Size heterogeneity of affinity-labeled estrogen receptor in the ram hypothalamo pituitary axis. AB - The presence of multiple monomeric forms of estrogen receptor (ER) has been described in different target tissues. Using [3H]tamoxifen aziridine (TA) to covalently label ER and SDS-PAGE to analyze labeled products, ER forms were investigated in ram pituitary and hypothalamus. A major labeled protein of M(r) 60,000-65,000 and a minor species of 50,000-55,000 were found in the pituitary cytosol covalently labeled with [3H]TA. In the hypothalamic cytosol, the major TA labeled species was the M(r) 50,000 form while the 65,000 ER was difficult to detect. Comparison of ER forms after in vitro translocation of the ER complex in purified nuclei of ram pituitary or hypothalamus again showed major ER forms of M(r) 65,000 and 50,000 for the glandular and nervous tissue respectively, suggesting a biological significance for the M(r) 50,000 species. A similar heterogeneity was also observed in male rats used as controls. Moreover, covalent labeling of cytosol from the pars tuberalis/median eminence area showed the presence of ER in this part migrating with a pattern between those of the hypothalamus and the pituitary. The ER heterogeneity was thus demonstrated in the hypothalamo-pituitary axis. The source of this heterogeneity could be: (1) different ER mRNAs according to tissue type; (2) a specific posttranslational processing such as a specific proteolytic activity within the nervous tissue. PMID- 8367032 TI - Stimulation of H3-histamine receptors increases the release of prolactin in male rats. AB - Histamine (HA) stimulates prolactin secretion via H1 and H2 receptors. In the present study, we examined the role of a third subtype of receptor recently described in brain, the H3-HA receptor, on prolactin secretion in male rats. R( )alpha-methyl-HA (alpha-MHA), a selective H3 receptor agonist, was injected into the lateral ventricle of the brain in freely moving rats. alpha-MHA produced a dose-dependent (1-5 micrograms) and long-lasting increase in plasma prolactin levels. This increase was observed from 15 to 60 min after injection of alpha MHA. Its stimulatory action was prevented by thioperamide (20 micrograms i.v.t), a selective H3 antagonist. This compound, injected intraventricularly, lacked effect by itself on basal plasma prolactin levels. Neither pyrilamine (H1 antagonist; 60 micrograms i.v.t.) nor ranitidine (H2 antagonist; 60 micrograms i.v.t.) affected alpha-MHA-induced prolactin release. The stimulatory effect was still present when brain HA was depleted by alpha-fluoromethylhistidine (30 mg/kg i.p.). Our findings suggest that alpha-MHA evokes prolactin release by activation of postsynaptic H3 receptors. PMID- 8367033 TI - Effects of single and repeated exposures to ethanol on hypothalamic beta endorphin and CRH release by the C57BL/6 and DBA/2 strains of mice. AB - Ethanol has been shown to enhance the in vitro release of hypothalamic beta endorphin (beta-EP). In the present study, the pattern of beta-EP release by the hypothalamus of two strains of mice, bred selectively for their preference (C57BL/6) or aversion (DBA/2) to ethanol, was investigated using a tissue perifusion system. The tissues were perifused with 20 mM ethanol for 30 min and the immunoreactive beta-EP content was estimated in perifusates collected every 2 min. Ethanol induced an enhanced release of hypothalamic beta-EP characterized by an initial spike followed by a gradual decrease toward baseline levels in both strains of mice. The ethanol-induced increase in beta-EP release by the hypothalamus of the C57BL/6 mice was more pronounced and longer lasting than that by the hypothalamus of the DBA/2 mice. Similar to beta-EP, an immediate sharp increase of corticotropin-releasing hormone (CRH) release was induced by ethanol which, however, did not present a spike but was maintained significantly higher than spontaneous release for the duration of ethanol exposure. Both ethanol induced beta-EP and CRH release returned to basal levels within 10 min following removal of ethanol. That beta-EP levels did not remain elevated for the duration of ethanol exposure was not due to tissue depletion of releasable beta-EP pool, since exposure of the hypothalami to 10(-8) M CRH for 10 min, immediately after the perifusion with 20 mM ethanol, resulted in a large increase of beta-EP release. A second ethanol exposure 30 min after the first one did not induce an increase in beta-EP release. However, when the recovery period from the first ethanol exposure was extended to 60 min, a significant increase in the release of hypothalamic beta-EP was observed from the hypothalamus of the C57BL/6 but not of the DBA/2 mice. It is concluded that hypothalamic endorphinergic neurons present a fast, transient increase of beta-EP release in the presence of 20 mM ethanol, and become insensitive to subsequent ethanol exposures for a period of about 60 min. In addition, genetically determined differences exist with regards to the magnitude and duration of the ethanol-stimulated release of beta-EP, as well as on the length of the ethanol nonresponsive period. These differences may explain in part the differences in the voluntary ethanol consumption exhibited by these strains of mice. PMID- 8367034 TI - A tissue culture model of the hypophysiotrophic CRF producing neuronal system. AB - To investigate functional and chemical properties of anatomically characterized corticotropin-releasing factor-41 (CRF-41) producing neurons in vitro, hypothalamic slices of 6-day-old rats were maintained in culture for up to 6 weeks using a modified roller culture technique. This technique yields thick (100 microns) slices that contained an average of 300-400 CRF-41-immunostained neurons. The majority of CRF-41-positive cells were of small size (12-15 microns in diameter), and contained CRF-41-labeled dense core vesicles of 100 nm diameter as detected by electron microscopic postembedding immunocytochemistry. These cells represented the only CRF-41-positive cell population in the culture. Light microscope double immunolabelling of colchicine-treated cultures kept in a serum containing media (SCM) indicated that about 60% of these CRF-41-positive neurons contains detectable levels of vasopressin-associated neurophysin (VP-NP). Culturing slices in serum-free, chemically defined media (SFM) resulted in an increased VP-NP immunostaining: parvicellular neurons labeled for both CRF-41 and VP-NP could be detected without colchicine treatment, and practically all CRF-41 positive neurons expressed VP-NP immunoreactivity. At the electron microscopic level there was a significant increase in VP-NP labeling density in the dense core vesicle compartment of CRF-41-positive varicosities. Adding dexamethasone (10 nM) to the SFM restored the staining pattern originally observed in SCM. Hence, the increased VP-NP and CRF-41 immunostaining after culturing CRF-41 neurons in SFM is most likely due to the absence of inhibitory glucocorticoids. The capacity of cultured paraventricular cells to release CRF-41 was assessed using an immunoassay. Unstimulated (basal) secretion of CRF-41 was not altered by five successive samplings at 2-hour intervals and stimulation of the same culture with 56 mmol K+ significantly increased (2-3 times) the CRF-41 content in the medium. The presence of dexamethasone (10 nM) in SFM induced a 6-fold reduction of K(+)-stimulated CRF-41 release and a 5 times reduction in tissue content in relation to cultures maintained in SFM without dexamethasone. In summary, we have demonstrated that cultured CRF-41 cells display morphological and biochemical features, as well as responsiveness to glucocorticoids, that is reminiscent to the situation in vivo. Thus, the model is well suited for studies of hypophysiotrophic CRF-41 cell functions. PMID- 8367035 TI - Sinoaortic denervation alters the molecular and endocrine responses to salt loading. AB - Neuroanatomical and physiological evidence indicates that baroreceptors influence hypothalamic vasopressin (VP) and oxytocin (OT) neurons. We evaluated the effects of sinoaortic denervation (SAD) on the molecular and endocrine response to salt loading. Sham-operated or SAD rats were given a 2% NaCl solution to drink for 72 h. A group with limited salt water intake was included as a second control because the denervated rats consumed less salt than the controls. Plasma VP, OT and osmolality and posterior pituitary peptide content were measured. Brains were processed for evaluation of VP and OT mRNA expression using in situ hybridization with computer quantitation. Salt loading produced equivalent increases in plasma VP and OT in the control and SAD groups, however, there was a greater depletion of posterior pituitary peptides in the denervated animals. Salt loading produced significant decreases in pituitary VP and OT in the SAD animals, 69.8 +/- 8.4% and 68.3 +/- 4.0%, respectively. In the control groups, there was no decrease in VP content and a decrease in OT only in the control ad lib group. The peptide mRNA response to salt loading was also altered in the denervated rats. There was a significant increase in the area and intensity of the labeling for OT mRNA in the PVN in the SAD salt group. The control salt rats showed an increase in the SON and the salt-limited group showed no changes. For VP mRNA, the only change noted was in the SON of the salt-loaded SAD animals. These results show that chronic denervation of arterial baroreceptors augments the hypothalamic VP and OT response to salt loading.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367036 TI - Prolactin receptors in dove brain: autoradiographic analysis of binding characteristics in discrete brain regions and accessibility to blood-borne prolactin. AB - Film autoradiography and densitometry were employed to obtain a detailed map of prolactin (PRL) receptor distribution in ring dove brain and to characterize the affinity, capacity, specificity, and in vivo saturability of 125I-ovine PRL binding in individual brain regions. Significant specific binding was detected in choroid plexus and in a variety of forebrain and midbrain sites, with highest levels observed in the preoptic area, tuberoinfundibular region, lateral hypothalamic area, and the suprachiasmatic, paraventricular, and ventromedial hypothalamic nuclei. A comparison of PRL receptors in the choroid plexus, preoptic area, ventromedial nucleus, suprachiasmatic nucleus, and tuberal hypothalamus revealed significant regional differences in binding capacity, but not differences in binding affinity (Kd = 0.4-0.9 nM; Bmax = 6-14 fmol/mg protein). Unlabelled ovine PRL proved to be an effective competitor of labelled ovine PRL at concentrations of 43 pM, 0.43 nM, and 4.3 nM in the choroid plexus and in 5 diencephalic areas. In contrast, no significant competition was observed in any of these brain areas in tests with unlabelled turkey GH, ovine GH, or ovine LH at similar concentrations. Unlabelled ovine PRL (37 nmol) significantly reduced the uptake of 125I-ovine PRL (37 pmol) in the preoptic area, tuberal hypothalamus, and bed nucleus of the pallial commissure at 2 h after intravenous injection. In addition, specific binding of 125I-ovine PRL in vitro was reduced by over 67% in these brain areas and in several other brain regions following a 7 day period of systemic ovine PRL administration. These results indicate that PRL receptors in different regions of the dove brain exhibit similar binding characteristics. In addition, they suggest that at least some of these PRL sensitive brain loci are accessible to blood-borne hormone. PMID- 8367037 TI - Distribution of estrogen receptor-immunoreactive cells in the preoptic area of the ewe: co-localization with glutamic acid decarboxylase but not luteinizing hormone-releasing hormone. AB - Using immunocytochemical techniques we have examined the distribution of cells containing estrogen receptors (ERs) in the preoptic and anterior hypothalamic regions of short-term (1 week) ovariectomized ewes. Subsequent double-labelling experiments examined the co-localization patterns of ER and luteinizing hormone releasing hormone (LHRH) or glutamic acid decarboxylase (GAD) immunoreactivities. ER-immunoreactive (-IR) cells were identified throughout the central and medial aspects of the preoptic area in a continuum which begins at the level of the organum vasculosum of the lamina terminalis and terminates in the caudal anterior hypothalamic area. A conspicuous sub-population of densely clustered ER-IR cells was identified within this distribution extending from the central region of the preoptic area into the bed nucleus of the stria terminalis. ER-IR cells were also identified in the ventrolateral septum and supraoptic nuclei. Double-labelling experiments showed that although rostral LHRH neurons were surrounded by ER-IR cells, they did not themselves possess ER immunoreactivity. In marked contrast, we estimate that approximately 40% of GAD-IR cells in the central aspect of the medial preoptic area are immunoreactive for the ER and that these cells account for nearly 30% of all ER-IR cells in this region. These results indicate that, in common with other species, LHRH neurons in the ewe do not possess ERs and suggest therefore, that these neurons are unlikely to be modulated directly by circulating estrogens. However, large numbers of adjacent GABA neurons possess ERs and may comprise a major neuronal population mediating gonadal steroid input to LHRH neurons. PMID- 8367038 TI - In vivo release of neurotensin from the median eminence of ovariectomized estrogen-primed rats as estimated by push-pull perfusion: correlation with luteinizing hormone and prolactin surges. AB - In order to assess the physiological role of neurotensin (NT) in regulating the secretions of luteinizing hormone (LH) and prolactin (PRL), we examined whether the in vivo release of NT from the push-pull cannulated median eminence (ME) was altered in association with the LH and PRL surges in free-moving ovariectomized rats primed with estradiol. For comparison, LH-releasing hormone (LHRH) was also measured in the same perfusates from the ME in which NT was determined. NT and LHRH in the ME started to significantly increase roughly concurrently with the initial significant rises in LH and PRL in the plasma, and the highest levels of the neuropeptides clearly preceded the peak levels of LH and PRL. These in vivo data strongly suggest that NT, independently of or in concert with LHRH, may have a facilitatory role in the generation of estradiol-induced LH surge. In addition, these data may not disagree with a similar facilitatory role of NT in the PRL surge. This is the first characterization of the temporal profile of NT secretion in rat ME in terms of its relationship to the estradiol-induced surges of LH and PRL. PMID- 8367039 TI - Mixed vascular malformations of the brain: clinical and pathogenetic considerations. AB - The clinical relevance of any scheme for classification of vascular malformations of the brain remains controversial. Widely accepted pathologic classifications include discrete venous, arteriovenous, capillary, and cavernous malformations. Of 280 cases of possible vascular malformations evaluated by a single cerebrovascular service during a 5-year period, 14 were instances of mixed vascular malformations including definite features of more than one pathologically discrete type of malformation within the same lesion. There were six instances of mixed cavernous and venous malformations in the same lesion; in all instances, the cavernous malformation accounted for the clinical presentation. There were three cases of mixed venous and arteriovenous malformations (arterialized venous malformations), presenting with the typical histoarchitectural appearance of a venous malformation, but with arteriovenous shunting; all cases were symptomatic, two with hemorrhage and one with focal neurological symptoms. There were five cases of predominantly cavernous malformations with features of arteriovenous malformation or capillary telangiectasia in the same lesion. These five cases presented clinically as angiographically occult lesions indistinguishable from a cavernous malformation. Lesions including a venous malformation were recognizable preoperatively because of characteristic imaging features of the venous malformation. Other mixed vascular malformations were indistinguishable on diagnostic studies from pure cavernous malformations. Of the 14 mixed vascular malformations, 11 included a cavernous malformation that was usually responsible for the symptomatic presentation. In the other three cases, manifestations of clinical lesions were due to arteriovenous shunting within a venous malformation. We conclude that mixed vascular malformations of the brain are rare entities with distinct clinical, radiological, and pathological profiles. Their identification generates several hypotheses about common pathogenesis or causation-evolution among different types of lesions. PMID- 8367040 TI - Emergent aneurysm clipping without angiography in the moribund patient with intracerebral hemorrhage: the use of infusion computed tomography scans. AB - The authors report their experience with 25 patients (mean age, 44.3 +/- 12.1 years) with an intracerebral hematoma (ICH) from a ruptured aneurysm who were emergently operated on without angiography. Instead, preoperative high-resolution infusion computed tomography (CT) scans were used to identify the aneurysm causing the hemorrhage. In all patients, the preoperative Glasgow Coma Scale score was < 5 and brain stem compression was evident. ICH was present in the frontal or temporal lobe and was often associated with intraventricular hemorrhage (n = 17) and significant (> 1 cm) midline shift (n = 18). Infusion CT scans correctly identified the aneurysm in all patients (middle cerebral artery, 18; posterior communicating artery, 2; carotid bifurcation, 3; anterior communicating artery, 2). Partial evacuation of the hematoma guided by infusion CT scan was usually required first to clip the aneurysm definitively using standard microvascular techniques. Intraoperative rupture occurred twice, and temporary clips were used on four occasions. Lobectomy (n = 8), decompressive craniotomy (n = 15), and ventriculostomy (n = 8) were required to control cerebral swelling. All patients underwent postoperative angiography to confirm aneurysm obliteration. Eleven unruptured aneurysms were subsequently identified. Nine had been predicted by infusion scan. Twelve patients survived, eight of whom were only moderately disabled and were independent at 6-months' follow-up. Of the 13 patients who died, all except one died within 4 days of admission. The authors conclude that although angiographic verification before aneurysm surgery is preferable, in the moribund patient with intracerebral hemorrhage, infusion CT scanning provides sufficient information concerning vascular anatomy to allow rational emergency craniotomy and aneurysm clipping. PMID- 8367041 TI - Tumor prostaglandin levels correlate with edema around supratentorial meningiomas. AB - The pathophysiological mechanisms to explain peritumoral edema have not been clarified. Multiple aspects of brain edema secondary to supratentorial meningiomas were prospectively investigated in a group of 29 patients who underwent surgery consecutively. Sixty-nine tumor samples were analyzed for prostanoid levels. Levels of 6-keto-PGF1 alpha, the stable metabolite of prostacycline, were found to correlate well with the extent of edema (r = 0.51, P < 0.01). The ratio, 6-keto-PGF1 alpha x PGE2/TXB2, was found to have the best correlation with edema index (extension/tumor volume) (r = 0.69, P < 0.005). A case of a hemangiopericytic meningioma with the largest edema extent within the study group also exhibited the highest level of 6-keto-PGF1 alpha (2420 pg/mg protein). Steroid treatment (dosage, duration of therapy, and their product) did not correlate with prostaglandin levels. These findings may explain the inconsistent clinical effects of steroids on meningioma-induced edema. Possible explanations for this phenomenon are discussed. Otherwise, histology, pathological features of tumor aggressiveness, or mechanical parameters, such as its volume, location, and insertion site, did not correlate well with edema parameters or with prostaglandin levels. Similarly, tumor water content, imaging parameters in computed tomography and magnetic resonance, and operative findings (including dissection plane, vascularity, and tumor firmness) did not correlate well with edema parameters. Although a direct cause-effect relationship between prostaglandins and peritumoral edema is not conclusively established, the circumstantial evidence of the ability of prostaglandins to induce vasogenic brain edema and the robust association with peritumoral edema is persuasive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367042 TI - Immunohistochemical detection of female sex hormone receptors in meningiomas: correlation with clinical and histological features. AB - Sixty-one meningiomas from 60 patients were screened for estrogen receptors and progesterone receptors (PgR) with monoclonal antibodies in an immunohistochemical assay. In addition, 43 of the cases were evaluated for tumor size and peritumoral edema, as seen on computed tomographic scans and magnetic resonance images. Sixty one percent of the tumors contained significant amounts of PgR, whereas no estrogen receptor-positive tumor was observed. Thirteen percent of all tumors were classified as nonbenign variants (atypical and anaplastic meningiomas) and were more frequently found in male patients (P < 0.05). Nonbenign tumors more frequently showed an absence of PgR (P < 0.05), and there was a tendency for PgR negative tumors to be larger than PgR-positive ones. No correlation was found between PgR status and edema. It is concluded that PgR status in meningiomas is related to tumor differentiation and may be of prognostic value with regard to biological behavior and clinical outcome. PMID- 8367043 TI - Intracranial hydatid cysts in children. AB - Brain involvement in hydatid disease occurs in 1 to 2% of all Echinococcus granulosus infections. Fifty to 75% of intracranial hydatid cysts are seen in children. This study included 19 children who underwent surgery for intracranial hydatid cysts between January 1979 and September 1992. There were 12 boys and 7 girls, ages 3 to 16 years (mean, 8.1 yr). Headache and vomiting were the predominant symptoms. Papilledema was present in 16 patients, and 2 patients had secondary optic atrophy. A round, cystic lesion without perifocal edema and rim enhancement was detected on the computed tomographic scans of 13 patients. The cystic lesions with rim enhancement and perifocal edema were noted on the computed tomographic scans of 3 patients. Of these three patients, two subsequently had a recurrence. Total removal of the cyst without rupture was achieved in 12 patients. Only a 3-year-old boy in whom the cyst ruptured at surgery died. Seven patients in whom either the hydatid cyst ruptured at surgery or there was systemic hydatid disease received mebendazole therapy. Mebendazole seems to be effective in hydatid disease. Cerebral hydatid cysts should be removed in toto without rupture. The preoperative diagnosis is very important in planning surgery. When a cystic lesion is detected on computed tomographic scan, hydatid disease should be taken into consideration in countries where hydatid disease is endemic. PMID- 8367044 TI - Accidental head trauma and retinal hemorrhage. AB - Retinal hemorrhage and intracranial hemorrhage in a child with little external evidence of trauma and with a poorly documented history are considered pathognomonic child abuse. The mechanism and magnitude of force required to produce the injuries are seldom witnessed or known. This study was designed to determine the incidence of retinal hemorrhage in pediatric head injuries under known accidental circumstances, in association with forces sufficient to cause skull fracture and/or intracranial hemorrhage. Of 525 consecutive hospital admissions for head injuries, 200 children filled these criteria. Thirty children were excluded because of suspected child abuse or gunshot wounds. Of the remaining 170, 140 were evaluated by an ophthalmologist for retinal hemorrhage. Two children, who were both involved in side-impact car accidents, had retinal hemorrhages in associated with severe head injury. Retinal hemorrhage occurs rarely in accidental head injury and is associated with extraordinary force. PMID- 8367045 TI - Flexible endoneurosurgical therapy for aqueductal stenosis. AB - We successfully managed 11 patients with aqueductal stenosis of adult or adolescent onset, with no mortality or significant morbidity, by using a flexible ventriculoscope to perform either a third ventriculostomy or an aqueductal plasty. A flexible fiberoptic ventriculoscope and its accessories were newly developed, and surgical techniques were improved. For all patients, cinemagnetic resonance imaging was a critical part of the preoperative and postoperative evaluation of cerebrospinal fluid flow in the third ventricle and in the aqueduct of Sylvius. All of the 11 patients showed patency to cerebrospinal fluid flow at the aqueduct of Sylvius and the floor of the third ventricle. Only one patient subsequently required a lumboperitoneal shunt. Flexible endoneurosurgical management is simple and safe and allows in situ observation and the ability to perform biopsies. Therefore, flexible endoneurosurgical third ventriculostomy and aqueductal plasty are now considered our treatment of choice for aqueductal stenosis in adults and adolescents. PMID- 8367046 TI - The combined pterional/anterior temporal approach for aneurysms of the upper basilar complex: technical report. AB - A technique for achieving a combined pterional (subfrontal) and anterior temporal exposure for aneurysms of the upper basilar complex is described. The technique is not new, but it does involve several modifications not previously described. A standard pterional skin incision that extends below the zygoma just anterior to the tragus is used. The skin flap is separated from the temporal fascia down to the fat pad over the zygoma; at this point, the superficial layer of the temporalis fascia is incorporated and retracted with the skin flap to expose the zygomaticofrontal process and the zygomatic arch. The muscle is cut anteriorly and inferiorly and is retracted posteriorly over the ear. The bone flap includes the anterior temporal squama down to the temporal floor anteriorly. The pterion and the sphenoidal wings are drilled so as to expose completely the dura over the anterior temporal pole. After opening the dura on a flap centered on the sylvian fissure, the medial cisterns are opened widely and the fissure is opened all the way to the middle cerebral bifurcation. Posterolateral temporal retraction and, when necessary, subpial resection of the anteromedial portion of the uncus enhance the exposure posterolateral to the oculomotor nerve. The advantages of this combined approach are as follows: it combines the more anterior angle of vision offered by the pterional approach with the lateral line of vision offered by the subtemporal approach; it eliminates the need for temporal lobe elevation and it allows simultaneous clipping of other aneurysms of the ipsilateral anterior circle of Willis; and it also reduces the frequency and severity of oculomotor palsy, when compared with the subtemporal approach. PMID- 8367047 TI - Magnetic source imaging: a review of the Magnes system of biomagnetic technologies incorporated. AB - Magnetic source imaging (MSI) is a new, noninvasive technique for defining the relationship between brain function and structure on a patient-to-patient basis. It achieves this by combining detailed neurophysiological data derived from magnetoencephalography with high-quality neuroanatomical data derived via magnetic resonance imaging. By the use of mathematical models, the spatial locations of those neurons that generate neuromagnetic signals of interest are estimated and subsequently marked on spatially aligned magnetic resonance images. There are three prominent types of clinical MSI examinations. These are: 1) functional mapping examinations in which sensory and motor functions are localized; 2) examinations of interictal epileptiform activity; and 3) examinations of abnormal low-frequency magnetic activity, which has been found to be present in a wide range of pathophysiological conditions. Functional mapping provides useful information regarding the relationship between the cortical representation of eloquent function and the location of pathological lesions that may be surgically resectable. This application is of particular utility in cases of intracortical masses that distort and obscure the local neuroanatomy. By defining the primary sites of interictal epileptiform activity, MSI examinations are useful in the surgical planning for the implantation of depth electrodes and the planning of partial lobectomies. Abnormal low-frequency magnetic activity appears to be a neurophysiological correlate of ischemic penumbra associated with stroke, neoplasms, and vascular malformations. Abnormal low-frequency magnetic activity has also been found to be present in several other conditions, including head trauma and psychiatric dysfunction, although the exact pathophysiological mechanisms are presently unclear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367048 TI - Noninvasive presurgical neuromagnetic mapping of somatosensory cortex. AB - Rapid presurgical neuromagnetic localization of the somatosensory cortex was performed successfully on five patients with a large-array biomagnetometer by a protocol called magnetic source imaging (MSI). Determination of the location of the central sulcus is important in assessing operative risk and determining the optimal operative approach to structural lesions in the vicinity of the motor strip. The use of magnetic resonance imaging anatomical methods and intraoperative visual identification can be imprecise, whereas invasive localization prolongs operative time, adds cost, and entails added risk. Until the recent development of large-array biomagnetometer systems, neuromagnetic localization of the central sulcus had been demonstrated in research but was so time consuming and laborious as to preclude routine clinical use. In this study, the validity of MSI localizations was confirmed intraoperatively by direct cortical recording of somatosensory evoked potentials and/or direct motor stimulation. Complete agreement was found between MSI and intraoperative mapping in locating the central sulcus. Objective confirmations considered together with the speed and reliability of the procedure and with the presurgical availability of the results suggests the potential utility of MSI for routine surgical planning. PMID- 8367049 TI - Functional neurosurgical simulation with brain surface magnetic resonance images and magnetoencephalography. AB - We present a novel noninvasive technique for functional neurosurgical simulation combining three-dimensional magnetic resonance imaging of the brain surface with somatosensory evoked magnetic fields (SEFs) in a case of subcortical brain tumor. The preoperative analysis using this technique revealed that the central sulcus was located between the SEF source projected onto the brain surface and the tumor. At the time of surgery, the central sulcus was clearly identified by phase reversal of the cortical recordings of somatosensory evoked potentials. The actual cortical anatomy and the maximum somatosensory evoked potential location showed excellent agreement with the preoperative analysis of the brain surface magnetic resonance images and the SEF source. The subcortical tumor, which was barely identifiable without reliable functional cortical anatomy, was easily found in the motor area, just before the somatosensory evoked potential (and SEF) source. The potential clinical application of this technique is discussed. PMID- 8367050 TI - Isolated paraplegia from a remote stab wound. AB - A stab wound to the right flank of a 24-year-old man produced immediate paralysis of both legs but spared sensation. Recovery was slow but sufficient to allow walking with a cane. Radicular artery interruption, in combination with systemic hypotension, is presumed to have caused selective watershed infarction of the spinal cord. Strokes of the spinal cord after trauma are rare, and those at a thoracic level usually represent delayed infarctions after pediatric chest or abdominal injuries. Our patient sustained an immediate and highly selective infarction. PMID- 8367051 TI - Three-dimensional analysis of the vascular system in the rat spinal cord with scanning electron microscopy of vascular corrosion casts. Part 1: Normal spinal cord. AB - Vascular corrosion casts of polyester resin in the normal spinal cord at C4-C6 and C7-T1 were inspected three-dimensionally by scanning electron microscopy in 13 rats. Arteries and veins were easily differentiated by the impression pattern of endothelial nuclei on the casts. The centrifugal arterial system from the sulcal arteries supplied most of the gray and white matter in the ventral and lateral spinal cord. Each sulcal artery supplied only one side of the cord. The average number of sulcal arteries was 2.6 per mm. The centripetal arterial system from the posterior spinal arteries fed the posterior gray and white matter. In contrast with classical concepts, there was no pial arterial plexus on the ventral and ventrolateral surface except for infrequent transverse branches from the anterior spinal artery. In the posterior columns, two types of large veins were identified: the posterior medial septal veins and the posterior oblique veins that drained the posterior columns, medial posterior gray matter, and posterior gray commissure. The remainder of the gray and white matter was drained by the sulcal veins and the radial veins. This method clearly demonstrates the three-dimensional structure of both the arterial and venous system in the rat spinal cord. PMID- 8367052 TI - Three-dimensional analysis of the vascular system in the rat spinal cord with scanning electron microscopy of vascular corrosion casts. Part 2: Acute spinal cord injury. AB - The purpose of this study was to investigate the vascular mechanisms involved in the pathophysiology of acute spinal cord injury. Vascular corrosion casts of traumatized rat spinal cords at C7-T1 were inspected by scanning electron microscopy. Nineteen rats were subjected to a 51g acute clip compression at C8-T1 and then underwent transcardial perfusion with polyester resin at 15 minutes, 4 hours, or 24 hours after injury. The injured spinal cord appeared almost avascular at the compression site, although the large vessels on the surface of the spinal cord were all intact. The sulcal arteries at the injury site frequently showed constriction, and the impressions of endothelial nuclei were more slender and less distinct in the constricted arterial casts. Extravasation of the injected resin at the injury site was observed most frequently in the 15 minute group. Poorly filled distal branches of the sulcal arteries were seen at the injury site in every group. Indeed, it was concluded that the disruption and occlusion of the sulcal arteries and their branches accounted for a considerable amount of the posttraumatic ischemia of the cord. Occlusion of the sulcal arteries in the anterior median sulcus at the injury site was more frequently observed in the 24-hour group than in earlier groups. This observation suggests that there was a progressive circulatory disturbance of the damaged sulcal arteries at the injury site. The 4- and 24-hour groups showed avascular areas extending longitudinally from the injury site in the posterior columns, probably the result of hemorrhage and venous obstruction. PMID- 8367053 TI - Appearance of a cavernous hemangioma in the cerebral cortex after a biopsy of a deeper lesion. AB - Cavernous hemangiomas are vascular malformations that can occur throughout the central nervous system. In certain patients, multiple lesions are known to occur. We present a patient with multiple cavernous hemangiomas who had a computed tomography-guided biopsy of a deep parieto-occipital lesion through a burr hole. Several passes of a biopsy needle were used. During a 5-year interval, the patient developed a new lesion directly under the burr hole on the cortical surface. The new lesion appears to have occurred from the implantation and growth of a cavernous hemangioma secondary to the biopsy. PMID- 8367054 TI - Inadvertent intraspinal placement of a Foley catheter in severe craniofacial injury with associated atlanto-occipital dislocation: case report. AB - A case of fatal, inadvertent, intraspinal placement of a Foley urinary catheter is presented. The patient suffered a severe craniofacial injury with life threatening epistaxis requiring emergent tamponade with two Foley catheters plus gauze packing. There was an associated atlanto-occipital dislocation. The mechanism of production is discussed, and guidelines to avoid this complication are outlined. PMID- 8367055 TI - Atypical meningioma of the third ventricle in a 6-year-old boy. AB - Pediatric meningiomas are uncommon. Those presenting in the third ventricle are rare; there are only 15 cases reported in the literature. We report an additional third ventricular meningioma in a 6-year-old boy. The tumor was resected via an anterior transcallosal interfornicial approach. Postoperatively, the patient exhibited a transient episode of mutism. Unlike previous reports, the pathological diagnosis of this lesion was an atypical meningioma. The presentation, management, pathological features, and postoperative course of our case are discussed and compared with previous reports. PMID- 8367056 TI - Meningioma in sigmoid sinus groove associated with dural arteriovenous malformation: case report. AB - A 65-year-old woman was evaluated for vertigo. Computed tomography and magnetic resonance imaging as well as angiography revealed the coexistence of a tumor at the junction of the right transverse-sigmoid sinuses, a dural arteriovenous malformation (AVM) of the right transverse sinus, and a right sigmoid sinus thrombosis. After transarterial embolization via the external carotid artery, the tumor was totally removed and the right transverse sinus was embolized with platinum coils and Surgicel. Postoperatively, the dural AVM was completely occluded, and the histological examination of the tumor showed it to be a transitional type of meningioma. It would be suggested that the right transverse sigmoid sinuses are involved by the meningioma to develop the sigmoid sinus thrombosis and the dural AVM of the transverse sinus, supporting an acquired origin of the dural AVM. PMID- 8367057 TI - Primary spinal extradural hydatid disease: report of a case with magnetic resonance characteristics and pathological correlation. AB - A rare case of hydatid disease of the lumbar extradural area and of the paravertebral muscles is reported. The patient underwent surgery, resulting in complete recovery. The limitations of computed tomography and the benefits of magnetic resonance imaging in forming a diagnosis are discussed. Magnetic resonance has been found to be an invaluable tool, not only in detecting the soft tissue extent of the disease but also in delineating the viability of hydatid cysts. PMID- 8367058 TI - Thecoperitoneal shunt for syringomyelia: report of three cases. AB - During 8 months, three consecutive cases of syringomyelia were treated by the placement of thecoperitoneal shunts. In the first two patients, the cord cavitation was idiopathic in one and thought to be related to spinal trauma in the other. In the third case, there was associated anomaly of the craniocervical junction of the Chiari I type. Surgery was followed by clinical improvement in all patients. Postoperative magnetic resonance images showed definite diminution of the syringomyelic cavity. The results of treatment seem to support the use of the technique as a primary treatment of syringomyelia associated with progressive myelopathy. PMID- 8367059 TI - Uterus-like mass of the conus medullaris with associated tethered cord. AB - A patient with a mass lesion of Mullerian origin associated with a spinal dysraphism is reported. The mass lesion was a genuine uterine formation, and a hemorrhage arose from a functional endometrium. A spinal dysraphism was associated, including a low-lying conus medullaris, a subcutaneous lipoma, and a sinus between the cul-de-sac and the lipoma. This ectopic and mature tissue may be differentiated from teratoma and endometriosis. PMID- 8367060 TI - A percutaneous epidural screw electrode for intracranial electroencephalogram recordings. AB - A new epidural electrode for monitoring brain electrical activity is described. The electrode is a tapered screw that is easily inserted percutaneously and removed without general anesthesia. The epidural screw has been used without complications for ictal and interictal electroencephalogram recordings in four patients with medically refractory complex-partial seizure disorders. The epidural screw electrode offers the advantages of easy insertion and removal, patient comfort, artifact-free electroencephalogram recordings, and minimal risk of intracranial infection or hemorrhage. PMID- 8367061 TI - Clinical predictors of abnormality disclosed by computed tomography after mild head trauma. PMID- 8367062 TI - Motor and sensory cortex in humans: topography study with chronic subdural stimulation. PMID- 8367063 TI - Bilateral carpal tunnel release at one operation: report of 228 operations. PMID- 8367064 TI - Clinical analysis of a series of vertebral aneurysm cases. PMID- 8367065 TI - [Non-palpable lesions of the breast. Analysis of 111 cases]. AB - The authors report a series of 111 cases of non-palpable breast tumours. Radiological examinations showed the following mammographic patterns: microcalcification (63%); irregular opacity and/or denseness (26%); opacity and low density microcalcifications (12%), to which 3 progressive risk rates were assigned (high, medium, low). Histological controls of the tumours showed a positive predictive value of 73% for mammographic patterns defined as "high risk". Localisation using a metal probe proved to be a simple and efficacious method which was well tolerated by patients. PMID- 8367066 TI - [Bilateral carcinoma of the breast. Presentation of a case series and review of the literature]. PMID- 8367067 TI - [Cervico-mediastinal goitre. Analysis of preoperative clinical symptoms]. AB - During past decades, a considerable and debated speculation about the classification of intrathoracic goitre was more and more developing. One of the most reliable classifications we share is that considering the degree of the intrathoracic extension of the thyroid gland: i) largely intrathoracic (more than 80%), ii) partially intrathoracic (more than 50%, but less than 80%), and iii) sub-sternal goitre (more than 50% holding in the neck). Consistently with the above mentioned classification, this report deals with ninety-seven cases of completely intrathoracic goitre (64 females and 33 males, aging between 29 and 78 years). Sixty-eight patients out of these showed a goitre reaching the upper aortic border; the other 29 patients had a thyroid gland exceeding this degree of extension. Therefore the intrathoracic goitre is a not frequent thyroid disease: in our series, it represents the 3.67% of 2641 surgical interventions on the thyroid gland from January 1984 to December 1990, that is to say the 20% of the so-called plongeant goitres undergoing surgery during the same years. The aim of this survey was to study the clinical features of the intrathoracic goitre and to have a therapeutic and prognostic assessment in this thyroid disease, before the surgical intervention. To this purpose, the prodromic symptom or sign, the clinical course before surgery, the clinical examination (peculiarly about the neck) and the laboratory findings at admission, the preoperative imaging study (chest X-ray, ultrasound examination, scintiscan and tomoscan finding) were reviewed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367068 TI - [Postoperative venous thromboembolism in bariatric surgery]. AB - The authors discuss the problem of venous thromboembolism as a complication of bariatric surgery. They consider obese patients at risk for these complications, even if different opinions exist about this topic in the literature. They report their experience in bariatric surgery consisting of 53 patients submitted to biliopancreatic diversion. Antithrombotic prophylaxis consisted for every patient in elastic bandaging of the lower limbs, preoperative hemodilution, early post operative mobilization, and subcutaneous heparin. Complications consisted in one popliteo-femoral deep venous thrombosis (DVT) (1.6%), and two pulmonary embolisms (PE) (3.2%) of which one caused patient's death; total morbidity for venous thromboembolism. These results compared with literature are similar with other series of bariatriac surgery and slightly higher than general surgery series. This difference is not however significant. Even in the absence of this significance, thromboembolism, as desumed from more than 2900 cases considered in the literature, remains the main cause of morbidity and mortality in the post operative course of bariatric surgery patients, deserving particular attention in terms of prevention, also because of difficulty existing in early clinical diagnosis of DVT in obese people. Further studies intended to identify pathogenesis and risk factors of venous thromboembolism in obese people will allow a more correct prophylactic and therapeutic approach. PMID- 8367069 TI - [Acute intestinal ischemia. Diagnosis and surgical treatment]. AB - The authors report their experience of 32 patients operated for acute intestinal ischemia. A massive intestinal infarction was diagnosed in 24 cases. The overall postoperative mortality rate was 72%. The postoperative survival rate was 20% after mesenteric infarction and 42% in patients with limited acute intestinal ischemia. The need for early specific diagnosis is stressed, because the therapeutic options vary widely in relation to different types of acute intestinal ischemia. Furthermore, the basic role of parenteral nutrition in postoperative treatment of short bowel syndrome is underlined. PMID- 8367070 TI - [Sigmoid volvulus]. AB - The authors report a retrospective study of four patients treated for sigmoid volvulus at the Clinica Chirurgica II of IRCCS Policlinico S. Matteo of Pavia between April 1974 and June 1989. They are collected from a series of 74 consecutive operations for colonic obstruction not related to hernias of the inguinal-crural region (incidence 5.4%). One patient died. The authors review the incidence, epidemiology, etiopathogenetic hypothesis, clinical patterns, nonoperative and operative therapeutic options of the affection. They emphasize the poor prognosis because the sigmoid volvulus usually occurs in elderly ill patients. PMID- 8367071 TI - [Congenital splenic cysts. Presentation of a clinical case]. AB - The authors describe a rare case of congenital splenic cyst, observed in a 22 year old female. Pathological and clinical aspects are discussed and the up-to date diagnostic and therapeutic approach is presented. PMID- 8367073 TI - [Rupture and migration of central venous catheter]. AB - In the period 1978-1990, 100 patients (44 males, 56 females) with various pathology, had a catheterisation of a central vein in the Hospital of Susa (TO). Subclavian vein was chosen with a percutaneous infraclavicular route. In 7 cases (7%) there were some mechanical complications, one of them was the accidental breakage of the catheter and its migration to the right heart. The authors describe this case and the possible cure by examining the most recent literature data. PMID- 8367072 TI - [Abdominal aortic aneurysm ruptured into the inferior vena cava. Presentation of a clinical case. Review of the literature]. AB - Rupture of the major veins is a rare complication of abdominal aortic aneurysms and is generally followed by sudden haemodynamic changes, whose importance is strictly dependent on the size of the fistula and rapidity of onset. The final result is invariably hyperdynamic congestive heart failure, oligoanuria and hyperazotemia, expression of renal insufficiency. Early recognition and surgical operation, together with appropriate postoperative intensive care, are the key for successful treatment of aorto-caval fistulas. Despite the improvement of surgical and anaesthesiology techniques, operative mortality rate still remains elevated (36%), but not higher than in other abdominal aortic aneurysms ruptures. The aim of this paper is to review the literature and to report one case of a seventy-year-old patient affected by an aorto-caval fistula and successfully treated in our Surgery Division. PMID- 8367074 TI - Injury: the medical and related costs in New Zealand 1990. AB - AIM: To describe the cost of inpatient admissions and emergency department attendances for injury at a major New Zealand hospital; and to extrapolate to indicative national costs for injury, with a view to facilitating decision making, in relation to injury prevention programs. METHODS: By using data from the patient management system database and the resource utilisation system operating at Dunedin Hospital to describe the utilisation spectrum for injury related events. RESULTS: The institutional cost of inpatient care for injury cases for the year ending 31 December 1990 amounted to $7,378,000, at an average of $3,020 a case. The costs for emergency department attendances (not resulting in admission) amounted to $2,585,000, at an average of $93 a case; the total of $9,963,000 equated to 15% of the hospitals annual operating budget. The most expensive causes of admission with injury were falls and motor vehicle traffic crashes. The commonest resulting injury was fractures of the lower limb, and the commonest and cumulatively most expensive injuries presenting at the emergency department were cuts, and sprains and strains. If these costs were extrapolated to New Zealand as a whole it would suggest hospital costs of approximately $457 million per annum; when taken in conjunction with other known medical and welfare costs this approximates to an annual bill to the state of approximately $1.2 billion per annum. CONCLUSION: Injuries are a significant, costly, potentially preventable, element of health care. The use of hospital data for the allocation of resources to preventive efforts to date, has been based primarily on hospital admission numbers. This study suggests that this is not however indicative of the costs to the state, and the use of financial and other utilisation data would assist in rationalising resource allocation to preventive programs. PMID- 8367075 TI - Home or hospital-based emergency care for chronic psychiatric patients? PMID- 8367076 TI - Medication and perception of dry mouth in a population of institutionalised elderly people. AB - AIM: (1) To estimate the prevalence of use of different medication categories; (2) to estimate the prevalence of xerostomia (dry mouth); and (3) to estimate the effects of xerostomic medication upon perceived dry mouth among institutionalised elderly people. SUBJECTS: A two-stage stratified random sample of three hundred and fifty-nine people aged 65 to 102 living in rest homes and geriatric hospitals in the Manawatu and Horowhenua districts. METHOD: Subjects were interviewed and dentally examined at their place of residence. Medication was noted from institutional records, and subjects' experiences of xerostomia were explored using the question "how often does your mouth feel dry?" RESULTS: The sample was found to be highly medicated, with a mean 3.6 different drugs per individual, and only 10% not taking any medication. Psychotherapeutics (42.3%), analgesics (32.9%), diuretics (31.2%) and laxatives (23.4%) were the most common drug categories. Of the 284 subjects who were able to answer, only those who were taking anticholinergic medication reported a higher prevalence of xerostomia. CONCLUSIONS: Institution-dwelling elderly people are a highly-medicated group. There is an increased risk of unwanted oral side-effects with certain drugs, and it is recommended that this is borne in mind when prescribing for elderly patients. PMID- 8367077 TI - Immunisation surveillance: a comparison of four methods in Canterbury. AB - AIMS: To evaluate four methods of immunisation surveillance by comparing the estimates obtained for Canterbury in the National Immunisation Coverage Survey with estimates calculated using data on immunisation distribution, general practitioner immunisation benefit claims and immunisation coverage at school entry. METHODS: Estimates were calculated using existing data sources on vaccine distribution, immunisation benefit claims, school entry immunisation coverage and live births in Canterbury. The survey was conducted according to a WHO protocol. RESULTS: The estimates based on vaccine distribution were of no use. The school entry data available did not allow complete evaluation of this method, which has some potential advantages. A number of inconsistencies were found between estimates from the survey and from immunisation benefit claims, between north and south Canterbury and between the two years for which estimates were calculated using benefit claims. CONCLUSIONS: It is concluded that the most practicable option, the immunisation benefit claim system, would require careful evaluation and improvement before it could be relied upon for immunisation coverage surveillance. The feasibility of each method as a means of immunisation surveillance is discussed. PMID- 8367078 TI - Acute myocardial infarction: experience at a rural hospital. PMID- 8367079 TI - The effects of user charges on the dispensing of prescription medicines: a survey of prescription charge payment in the Wellington region. AB - OBJECTIVE: The study aimed to examine the impact of user charges on the dispensing of prescription medicines. The effect of social class, customer type and number of items on the incidence of payment problems was examined. METHOD: The study employed a two week survey of 26 pharmacies randomly selected from Wellington Pharmacy Guild. Pharmacists completed a questionnaire on each occasion user charges led to a problem dispensing a prescribed medicine. Data collected included: type of problem encountered and its outcome, customer information (including the customer's pharmaceutical benefit category), and prescription information (including the number of items prescribed). RESULTS: The overall incidence of payment problems was 1.5% or 1 in every 66 prescription forms processed by the pharmacists. User charges resulted in medicine dispensing failure on 56% of the problem occasions. Customers incurred debt or were funded by a social agency on the remaining 44% of problem occasions. Fifty-three percent of dispensing failures resulted in non-collection of items at the end of the survey period. Thirty-four percent of debts were outstanding at the end of the survey. The incidence of all payment problems correlated with the social "need" score of the pharmacy area and was significantly higher for children's and student's prescriptions. CONCLUSION: User charges may provide a greater barrier to children, students and people living in areas of high social need. Ongoing evaluation of the impact of user charges is required to ensure improved prescribing is achieved equitably [corrected]. PMID- 8367080 TI - Sexual issues in the doctor/patient relationship. PMID- 8367081 TI - Antibiotic prophylaxis in surgery. PMID- 8367082 TI - Haematuria. PMID- 8367083 TI - Resource constraints--what do we tell our patients? PMID- 8367084 TI - Emotional health and cancer. PMID- 8367085 TI - Fallopian tube recanalisation. PMID- 8367086 TI - Fallopian tube recanalisation. PMID- 8367087 TI - NZMA pamphlet scheme. PMID- 8367088 TI - Tree nettle (Urtica ferox) poisoning. PMID- 8367090 TI - Hepatitis C in New Zealand. PMID- 8367089 TI - Hospital deaths and the coroner. PMID- 8367091 TI - Medical journals and the popular media. PMID- 8367092 TI - Maternal mortality in New Zealand. AB - New Zealand's maternal mortality rate in the triennium 1986-8 was reviewed in comparison with the rates from Australia and the United Kingdom during 1985-7. The New Zealand rate of 9.6 obstetric deaths/100,000 total births was higher than that for the United Kingdom (6.2) and Australia (4.4). Six of 16 deaths in New Zealand during the triennium were caused by sepsis, including five cases of puerperal infection with group A beta-haemolytic streptococci. Careful analysis of maternal deaths in New Zealand remains an important priority to provide audit of the performance of maternity services. PMID- 8367093 TI - Asymptomatic low bone mineral density in otherwise healthy people: four year follow up. AB - AIM: To determine the effect of screening a normal population for low bone density on lifestyle, subsequent bone density and fracture risk. METHOD: A cross sectional study of 726 subjects screened for low bone density identified 60 with bone density greater than one standard deviation below an age and sex matched mean. Those who accepted further assessment were followed clinically and with repeat bone densitometry for up to four years. Those declining assessment were contacted four years later and questioned about lifestyle changes and fractures. They were offered repeat bone densitometry. RESULTS: Twenty five subjects accepted intervention and were advised on lifestyle modification and treated with calcium supplements (18) calcitriol (5) or oestrogen (1). 22 of the 35 subjects who initially declined intervention volunteered to have their bone density repeated. Bone density increased in the group accepting intervention compared to the 22 subjects in the group who initially declined assessment (p < 0.05). Several laboratory investigations had a low yield. Lifestyle modification in the group declining assessment did not significantly affect subsequent bone density. Fractures occurred infrequently in both groups. CONCLUSION: After screening the normal population for low bone density, significant improvements in bone density can be achieved in patients accepting further intervention. PMID- 8367094 TI - Questionable methods of cancer treatment: time to face the facts. PMID- 8367095 TI - Sore throat presentation and management in general practice. AB - AIMS: To compare the characteristics of sore throat patients with their having normal throat, to measure the incidence of beta-haemolytic streptococcal growth in both groups, and to determine the clinical outcomes of treating sore throat patients without the aid of a throat swab. METHOD: Patients were from a suburban general practice. A three phased prospective study of consecutive patients with sore throats as their primary complaint, or with normal throats. RESULTS: Patients presented with a sore throat at a rate of 45 per 1000 consultations and those with normal throats presented at a rate of 379 per 1000 consultations. 43% of normal throat patients were male compared to 34% with sore throat (chi 2 = 4.62, p < 0.02). The incidence of beta-haemolytic streptococcal growth in sore throat patients was 123 per 1000 consultations per year. 23% of people 14 years and younger had a positive growth compared to 9% of people over 14 years of age. (chi 2 = 5.04, df = 1, p < 0.05). The sore throat presentation peaked over the late autumn to early winter months (June-July) but the beta-haemolytic streptococcal infection rate remained low throughout the year. A history of pain for less than three days and fever, and on examination large neck glands and pus on the tonsils were all positive clinical features for beta-haemolytic streptococcal infection. However use of clinical criteria alone meant 73% of patients with no beta-haemolytic streptococcal infection were falsely treated. CONCLUSION: Research is needed to develop guidelines for the management of sore throats in general practice. PMID- 8367096 TI - Comparison of Maori and European access to the Christchurch specialist diabetes complication screening clinic. AB - AIMS: To compare Maori and European utilisation of a specialist diabetes complication screening clinic. METHOD: All subjects attending the Christchurch specialist diabetes complication screening clinic over a 16 month period were asked to complete a questionnaire, which included data on age, ethnicity and diabetes treatment. The frequency of clinic attendance by age and ethnic group was then compared to the number of people in the general population, in the clinic catchment area. RESULTS: Of the 1356 subjects attending the complications screening clinic over the study period, 1347 completed the questionnaire. 1228 of the 1347 subjects (91.2%) were European and 84 (6.2%) were Maori. In the age range 45-64 years, Maori clinic attendance per 1000 general population was 25.6, compared to 7.57 per 1000 for Europeans. On a population basis, there were thus 3.4 times more Maori than Europeans attending the clinic. This figure is comparable with results from recent studies, which indicate that the prevalence of diabetes in this age range is about 3 to 5 times higher in Maori, compared to Europeans. CONCLUSIONS: Although this study failed to demonstrate evidence of inequality of health care utilisation, quantitative measures of utilisation are but one dimension of access to health care. Another dimension of health care access discussed in this paper, is the differing health care needs of different ethnic groups. PMID- 8367097 TI - Microtympanometry, microscopy and tympanometry in evaluating middle ear effusion prior to myringotomy. AB - OBJECTIVE: To determine the accuracy of a hand-held microtympanometer (Microtymp, Welch Allyn) used by a general practitioner when compared with findings at myringotomy. METHOD: Independent preoperative assessment of children's ears using microtympanometry by a general practitioner, microscopy and pneumatic otoscopy by a specialist otologist and impedance bridge tympanometry by a specialist audiologist were performed and compared with findings at myringotomy. SUBJECTS: Fifty children (100 ears) on the waiting list for bilateral myringotomies and ventilation tube insertion for recurrent acute otitis media or otitis media with effusion. RESULTS: Microscopy with pneumatic otoscopy had a 90.9% sensitivity and a 92.9% specificity in detecting middle ear effusions. Impedance bridge tympanometry had a 94.4% sensitivity and a 71.8% specificity if type B and C2 were combined to predict middle ear effusion. Microtympanometry had 100% sensitivity and 75% specificity if type B and C tympanograms were combined; if type B tympanograms alone were used, a sensitivity of 83.4% and specificity of 75% in predicting middle ear effusions was obtained. CONCLUSION: The Microtypm is a useful instrument in general practice for assessment of middle ear effusions as no ears with fluid were missed in this study if type B and C tympanograms were considered abnormal. The Microtymp would also be useful as a screening instrument by suitably trained personnel. PMID- 8367098 TI - Acute renal failure due to low osmolar radiographic contrast medium. PMID- 8367099 TI - Medical profile of patients with fractured neck of femur. PMID- 8367100 TI - Thin end of the wedge. PMID- 8367101 TI - The cut off wheel. PMID- 8367102 TI - Dyestuffs and bladder cancer. PMID- 8367103 TI - Fluoridation and fractures. PMID- 8367104 TI - Fluoridation. PMID- 8367105 TI - Iron deficient children. PMID- 8367106 TI - AIDS. PMID- 8367107 TI - Successful recruitment tool: a nurse extern program. PMID- 8367108 TI - Ethics in the OR: DNR and patient autonomy. AB - Suspending Do Not Resuscitate (DNR) orders during surgery may undermine a patient's right to self-determination. A Nursing Ethics Committee together with a Clinical Ethics Committee formulate guidelines to consider when suspending or maintaining a patient's DNR order while in the operating room. A patient's autonomy must be recognized as well as the professional responsibilities of surgeons, anesthesiologists and nurses. PMID- 8367109 TI - Tying pay to performance: one critical care unit's approach. AB - This article describes development and testing of a tool for determining an appropriate reward for staff performance in a critical care area. Outlined is the process of identifying and quantifying appropriate merit increases based on bedside performance as well as participation in other unit, hospital, professional and community activities. Positive results are reported after one- and two-year use. PMID- 8367111 TI - No second license. PMID- 8367110 TI - Restraining cognitively impaired nursing home residents. AB - Patterns of physical restraint use were measured according to time of day, location on the unit, and persons in the environment on three units of one long term care facility. An in-depth examination clarifies aspects of temporal, environmental and social conditions under which restraint use typically occurs in cognitively impaired and agitated nursing home residents. PMID- 8367112 TI - Failure to assess. PMID- 8367113 TI - If you don't read this, you're missing out. PMID- 8367114 TI - When virtue becomes vice. PMID- 8367115 TI - The path of legislation: best opportunities for nurses' input. PMID- 8367116 TI - When work redesign prompts unionization activity. American Organization of Nurse Executives. PMID- 8367117 TI - Case management and caring behavior. AB - A conceptual framework using the 10 caring behaviors described by Watson clarifies an aspect of one hospital's nursing focus, means and goals. Through the use of this model, case managers develop transpersonal or empathetic relationships with patients in the hospital and in the community. The outcomes indicate that caring relationships promote self-healing and self-actualization. PMID- 8367118 TI - Clinical nurse case management: a service line approach. AB - Quality improvement and cost-effective outcomes are achieved through an alliance with clinical or "internal" and community care management. Quality and cost outcomes during the acute-care phase for 25 elective case managed patients were compared against a control group of 25 non-case managed patients. Results reveal improved preoperative resource utilization and patient education. PMID- 8367119 TI - Starting a hospital-based home health agency: Part II--Key success factors. AB - In Part II of a three-part series, the financial, technological and legislative issues of a hospital-based home health-agency are discussed. Beginning a home healthcare service requires intensive research to answer key environmental and operational questions--need, competition, financial projections, initial start-up costs and the impact of delayed depreciation. Assessments involving technology, staffing, legislative and regulatory issues can help project service volume, productivity and cost-control. PMID- 8367120 TI - Peer review for nurse managers. AB - One hospital's task force developed an evaluation tool specific to the nursing supervisor job description. This tool measures performance and enhances group communication. PMID- 8367121 TI - The "C"s in excellence: choice and change. AB - Today's competitive healthcare world mandates excellence. Two aspects of excellence, choice and change, are part of the never-ending cycle when giving quality patient care. Managers can enable others to initiate change when needed which establishes the core of management and tomorrow's realities for progress, performance and patient care. PMID- 8367122 TI - Accepting and refusing assignments. AB - Guidelines define the professional, ethical and legal responsibilities involved when challenging or delegating patient assignments. Maintaining safe nursing practice levels is possible through such alternatives as enabling practice environments and cross-training. These significant factors identify options available to nurse managers and their staff without compromising patient safety. PMID- 8367123 TI - Unsafe at any price. PMID- 8367124 TI - Justifying an obstetrics early discharge program. AB - A clinical conclusion from a research article, applied hypothetically to a nursing administration problem, demonstrates the importance of applying research to practice and sharing the results with the profession at large. This proposal identifies a needed service, its market and the means to implement the service- developing an early discharge program for mothers and their newborns. PMID- 8367125 TI - Patient-focused care: is it for your hospital? AB - Advocates of Patient-Focused Care (PFC) claim that a win-win resolution to the cost/quality dilemma can be achieved by placing the patient's concerns at the center of planning. With the patient as the central focus, a whole new paradigm of care emerges which links all components of systems redesign work with a common, defining purpose. Before embarking on such a change effort, planners should carefully examine PFC assumptions for relevance to their specific environment. PMID- 8367126 TI - Southern California Edison integrates management of employee disabilities. PMID- 8367127 TI - Industry profile: food processing. Ergonomic controls cut the shackles of meat packing's cumulative traumas. PMID- 8367128 TI - Wellness strategies help workers adopt healthy habits in lifestyles. PMID- 8367129 TI - Workplace statistics can't cut to the heart. PMID- 8367130 TI - Fertility after the age of 40. AB - There is approximately a 50% decrease in the fertility rate of unselected women attempting pregnancy at age 40 or older compared with younger women and a two to three fold increased rate of spontaneous abortion. Approximately 45% of older women achieve a term outcome, however. Proper counseling of the older patient should include a realistic view of the following risks: a 30% to 50% reduced pregnancy potential, effect of pregnancy on other maternal illnesses, an increased risk of pre-eclampsia, hypertension, and diabetes, and an increased risk of chromosomal abnormalities, abortion, and stillbirth. Knowing these risks, additional testing for ovarian reserve may help to identify women with favorable indices in whom IVF, other forms of assisted reproduction, or surgery to restore fertility are most appropriate. Women with decreased ovarian reserve could be offered oocyte donation as an alternative to surgical correction for infertility, because pregnancy rates are excellent when donor oocytes are transferred to the uteri of women older than the age of 40. In short, age alone should no longer be a deterrent in the treatment of infertility. PMID- 8367131 TI - Contraception in women older than 40 years of age. AB - Women older than 40 years have high rates of unwanted pregnancy and abortion and traditionally have had limited choices of contraception agents. In today's market, oral contraceptives should be considered as should IUDs in properly screened candidates. Sterilization is effective for the couple who knows that they will have no more children. Mechanical methods are effective if used when intercourse tends to be a planned event and infrequent. With the variety of agents available in today's market, there is no reason why the unwanted pregnancy rate and abortion rate of the women older than 40 should not be reduced dramatically. PMID- 8367132 TI - Reproductive genetics for couples older than 40 years of age. AB - The counseling process, which involves genetic screening and prenatal diagnosis, is presented. Also addressed are the recent advances in assisted reproductive technologies, which may prove to be particularly useful for these patients. PMID- 8367133 TI - Diabetes in women older than 40 years of age. Social and medical aspects. AB - Prevention of Congenital Anomalies. Because the first few weeks after conception are a critical time in terms of embryopathy, good glycemic control should be established before conception in the pregestational diabetic and stringently maintained throughout the first trimester. Encouraging the diabetic woman to achieve stringent glycemic control before conception would virtually eliminate the excess risk of spontaneous abortion and anomalies. Prenatal Diagnosis. For all mature gravidas with diabetes, early prenatal diagnosis of chromosome abnormalities (mainly trisomies) and congenital anomalies should be determined through detailed ultrasound examination, fetal echocardiography, and alpha fetoprotein determinations. Glycemic Control. Stringent metabolic control is mandatory throughout pregnancy to prevent the risk for macrosomia and maternal accompanied medical complications, such as preeclampsia. Fetal Surveillance. Structured fetal surveillance evaluating fetal growth and well-being must be pursued throughout pregnancy. PMID- 8367134 TI - Pregnancy in women aged 40 and older. AB - Counseling patients about pregnancy at advanced maternal age is a difficult process. This is true both because our knowledge of the attendant risks is incomplete and still evolving, and because of the difficulties of assigning risks and addressing counterbalancing benefits for individual patients. There are a number of social and personal considerations involved in a decision to become a parent after the age of 40. Generally, older parents tend to be more mature, to be in stable and healthy marriages, and to have more financial and family resources to assist with the process of child rearing. Parents in their fifth decade, however, may complain of having less energy to devote to young children or may be at a stage in their careers in which they have less time for family participation than when they were younger. Also, grandparents, who can play a critical role in early childhood development, often have become too old to participate in that role or have died. All of these issues must be considered by parents contemplating late childbearing. A great deal has been written, much of it positive, even enthusiastic, about the quality of pregnancy and childbirth among older women. Nevertheless, much of the literature is difficult to interpret because of problems in controlling for confounding variables. In addition, much of the focus on so-called older women has been on those older than 35 years. In fact, the great majority of the medical literature concerning late childbearing relates to women between the ages of 35 and 40. The data that directly concern women in their fifth decade suggest that risks that began to accelerate after the age of 35 become considerably greater and increase more rapidly after the age of 40. Obviously, couples must decide what risks they are willing to accept and how these potential risks might be countervailed by the presumed advantages of parenthood relatively late in the reproductive years. There is convincing evidence to show that fecundity is decreased with advancing maternal age, and various forms of early pregnancy loss are increased. Thus, to delay childbearing results in a significant decrease in the likelihood of becoming pregnant or carrying a pregnancy to term. The possibility of genetic disorders is, as has been discussed previously, relatively easy to quantitate, and most age-related anomalies are amenable to prenatal diagnosis. It seems clear that women with underlying medical diseases, particularly hypertension and diabetes mellitus, contribute heavily to the excess morbidity and mortality associated with late childbearing.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8367135 TI - Medical management of abnormal uterine bleeding in the patient in her 40s. AB - A large proportion of AUB can be controlled successfully with a variety of pharmacologic agents. PMID- 8367136 TI - Management of the symptomatic fibroid in women older than 40 years of age. Hysterectomy or myomectomy? AB - Although complications resulting from a myomectomy are infrequent, the overall risk is probably greater than a hysterectomy. The effect of hysterectomy on the specific women is difficult to quantify, however. Supracervical hysterectomy is a reasonable alternative in the woman with a normal cervix. Moreover, repeated laparotomies are not particularly advisable. In a woman who has previously undergone a myomectomy and has had a recurrent symptomatic myomatous uterus, the decision must be made either to proceed with a repeat myomectomy or to perform a hysterectomy. The chance of successfully achieving a pregnancy after a second myomectomy may be less favorable than after a primary myomectomy. A myomectomy can be a difficult and often time-consuming procedure. With meticulous attention to technique, however, the procedure can be accomplished safely and effectively with relatively ensured hemostasis and minimal blood loss. A myomectomy affords the option of preserving the uterus in those patients with symptomatic uterine myomata who desire to preserve their reproductive organs. However, careful assessment with meticulous counseling of the patient is essential. The potential option for a hysterectomy must always be preserved. Hysteroscopic resection of submucous myomata with endometrial ablation has become the technique of preference in many cases. At the moment, abdominal myomectomy is the preferred technique for the removal of intramural and subserosal myomata. For the present, laparoscopic myomectomy must be viewed as being of very limited acceptability. PMID- 8367137 TI - Management of endometriosis in women older than 40 years of age. AB - Endometriosis in women older than 40 years of age presents unique therapeutic challenges to the practicing physician. Management requires the evaluation of reproductive goals and a determination of the objectives of therapy, including symptomatic relief and avoidance or delay of recurrence of disease. Important considerations in this age group include diminished fertility and impending menopause. The diagnosis and treatment for endometriosis-associated infertility must be undertaken in an expedient manner. Assisted reproductive technologies may be effective therapies for these patients. Conservative surgery may be necessary to preserve reproductive potential, but definitive surgery may be indicated in women with long-standing pelvic pain. Estrogen replacement therapy may be used in menopausal women with a history of endometriosis. PMID- 8367138 TI - Diet, exercise, and lifestyle in preparation for menopause. AB - This article reviewed conservative measures in dealing with issues of osteoporosis and cardiovascular disease prevention. The scientific evidence for each singular intervention is difficult to extract because there are so many confounding parameters. Moreover, improvement in nutrition and diet has its greatest impact on premenopausal women. Needless to say, a total health care approach is still beneficial: exercise, a low-fat and normocalcemic diet, and proper use of ERT. These issues need to be a concern for both the pre- and postmenopausal woman. Gynecologists as primary health care providers need to incorporate this knowledge into their practices. They should clearly understand both the benefits and shortcomings of a nutritional and exercise approach in osteoporosis and cardiovascular disease prophylaxis. In using this knowledge premenopausally, they can better prepare women for the menopause. PMID- 8367139 TI - Sexual function in the perimenopause. AB - Proper medical supervision and care, especially the prescribing of appropriate pharmacologic therapy, combined with factual information, supportive guidance, and sympathetic counseling will ameliorate or enhance sexual function in most perimenopausal women. The preventive steps taken during the midlife years will help build a solid foundation to ensure continued sexual activity and enjoyment for couples that extends into the menopausal, postmenopausal, and geriatric years. PMID- 8367140 TI - Cancer screening for women older than 40 years of age. AB - As women's doctors, we have a commitment and responsibility to promote effective cancer screening for cervical cancer and breast cancer. At present, the screening tests for ovarian cancer cannot be applied to the mass population. For an individual patient, however, the role of sonography, tumor markers, and physical examination need to be individualized. Clinicians need to look to the future for advances in screening for this dreaded disease. This article reviews and discusses the available cancer screening for cervical, breast, and ovarian cancer. PMID- 8367141 TI - Development and histology of fibrous architecture of the fetal temporomandibular joint. AB - The developmental history of the temporomandibular joint (TMJ) was investigated in 10 fetuses of 4 to 10 months of gestational age. The S-type structure of the disc is formed by the following bases: 1) the flat upper and concave lower surfaces of the disc; 2) thinner intermediate zone and thicker anterior and posterior bands; 3) the projection of the articular tuberculum and superoposterior growth of the condyle. The posterolateral part of the disc was the thickest and the corresponding part of the fossa was the deepest. The condyle was originally positioned beneath the part of disc that was considered the main force-bearing area. The distribution and arrangement of elastic and collagen fibers in the disc was proportional to disc function. Gross elastic fibers in the posterolateral part of the posterior band were connected with the upper head of the pterygoideus lateralis muscle fibers running medioanteriorly. They were indicated to be antagonistic with each other. At 4 months of gestational age, a few elastic fibers appeared in the bilaminar region and began to form bundles as the fetus grew. At full-term dense elastic fibers were found in the upper stratum of the bilaminar region. PMID- 8367142 TI - Lectin-binding glycoconjugates in the tongues of the rat and guinea pig as revealed by lectin-gold-silver methods. AB - Lectin-gold-silver (LT-G-S) procedures using two lectins (RCA-I and Con A) were applied to appropriately prepared paraffin sections of tongues in the rat and guinea pig. In the lingual mucous membranes of the rat and guinea pig, positive RCA-I-G-S and Con A-G-S reactions were obtained in the intercellular spaces and the cytoplasm of epithelial cells of the basal and intermediate layers respectively. Likewise, the LT (RCA-I and Con A)-G-S techniques gave rise to varying intensities of positive reactions in the serous and mucous gland acini, nerve and muscle fiber bundles and connective tissue elements. The results obtained in the present study indicate that in the rat and guinea pig tongues the histologic structures mentioned contain varying amounts of beta-D-galactose and alpha-D-mannose or alpha-D-glucose residues of glycoconjugates, and that such histochemical properties of some of the lingual structures can be correlated with their possible histophysiological functions. PMID- 8367143 TI - Ectopic kidney in front of the right common iliac artery and its blood vascular supply--a case report. AB - A discoid-shaped ectopic kidney located in front of the right common iliac artery was observed in a 71-year-old Japanese man. The right kidney was normally positioned, but the left kidney was not observed in the normal position. The ureter of the ectopic kidney descended laterally to the left ductus deferens. The ectopic kidney received three arteries which arose from the anterior aspect of the abdominal aorta. Two of the arteries supplied the left half of the kidney. The other supplied the right half and gave off two branches to the adipose tissue around the right kidney; these branches meant that this artery belonged to the right side. Venous drainage from the kidney was handled by two veins. One collected venous radicles from the right half of the kidney and flowed into the inferior vena cava; this vein belonged to the right side. The other served the left half and joined with the left lumbar vein, which finally drained into the left common iliac vein; this vein was attributed to the left side. The present ectopic kidney had a left-side ureter, and vascular supply on both the right and left sides. This disunity or dissociation of laterality in the vessels and the ureter seemed to be strongly related to the location of this ectopic kidney in the median region. PMID- 8367144 TI - The configuration of prepubertal hymen in Turkish population and its clinical aspect. AB - The importance of the hymenal configuration lies in the fact that it is accepted as an important sign of the virginity in many countries and also it needs a clearcut definition for the forensic evaluation of child abuse and rape. To improve understanding of configuration of the normal hymen we studied 100 prepubertal hymens. In addition to the most commonly seen types we found the fimbriated hymen at a high rate especially in adolescents. There was another configuration the appearance of which differed on each half of the vaginal orifice; one half had a labium while the other had fimbriae. The tagged type hymen was also encountered. PMID- 8367145 TI - Light- and electron-microscopic localization of basic fibroblast growth factor in adult rat retina. AB - An antiserum against basic fibroblast growth factor (bFGF) was characterized by immunoblot and used to localize bFGF-immunoreactivity in the adult rat retina. Crude homogenate of the retina, when examined with immunoblotting, exhibited a main band with the same molecular weight (18kDa) as bFGF. Light microscopic immunohistochemistry demonstrated intense bFGF staining in the photoreceptor outer segments and the outer plexiform layer, and weak immunostaining in some cells of the outer nuclear layer, inner nuclear layer and ganglion cell layer. The most intense bFGF-immunoreactivity was noted in glial (Muller) cells with vertically oriented thin processes. There were also immunoreactive pigment epithelial cells and mesenchymal cells in the choroid. Under electron microscopy, the outer plexiform layer was found to contain immunoreactive products exclusively in the axon terminals of photoreceptor cells which formed synapses with bipolar cell processes. The more widespread and uneven localization of bFGF immunoreactivity in the mature rat retina than previously demonstrated suggests that endogenous bFGF is involved in complex physiological events other than retinal regeneration and histogenesis. PMID- 8367146 TI - [Psychosomatic aspects of sterility and assisted reproduction]. AB - The authors survey the literature of psychosomatic aspects of infertility, in vitro-fertilization and embryo transfer. They emphasize the most important thesises of psychosocial and psychodynamical approaches. The changing of sexual and marital relationship of infertile couples are analysed as well. They call readers' attention to some critical points of doctor-patient and psychotherapeutical relationship. PMID- 8367148 TI - [New therapeutic possibilities in the management of congenital pulmonary valve stenosis]. AB - Data of 12 children (mean age = 3.1 yrs, range 0.4-11.1 yrs) with valvular pulmonary stenosis are reported. Balloon valvuloplasty was attempted for the treatment, first in the pediatric practice in our country. Echocardiography and cardiac catheterisation was used for the indication of the procedure and evaluation of the results. Strong correlation was found between the echocardiographic and haemodynamic data before (correlation coeff. = 0.9) and less strong after (correlation coeff. = 0.4) the procedure. As a result of the balloon dilatation the initial gradient of 62 mmHg (sd = +/- 17 mmHg) decreased to 20 mmHg (sd = +/- 10 mmHg) assessed by invasive technique. The difference is significant, p < 0.001. No major complication was observed. The procedure is recommended for widespread practice both in medical and financial sense. PMID- 8367147 TI - [Aspiration of barium contrast medium and its prevention]. AB - The authors have been noted aspiration bronchograms associated with barium filling study of the upper gastrointestinal tract in 58 patients involving basal medial, anterior, lateral and posterior segments of the lower pulmonary lobes, mammary segment of the middle lobe, moreover inferior lingula. In 75.9% of patients (44 cases) the barium meal got to bilateral basal medial, anterior and lateral segments. The 34 men and 24 women had a mean age of 69 years (range, 29 88 years). The aspiration was found 3.8-times more frequent after completion of patient's 50th year than before it observed. A transient tertiary mobility disorder of the esophagus, extrasystoles and tendency for collapse were on barium filling of bronchi. In 15 of the 18 patients the Valsalva's maneuver proved a pharyngomyodystonia. Carrying out of endoradiography depended on function of the lateral pharyngeal wall. The bronchi with physiological saline following aspiration of the contrast medium within 30 minutes were lavaged. PMID- 8367149 TI - [The use of a somatostatin analog (Sandostatin) in percutaneous drainage of pancreatic pseudocysts]. AB - The inflammatory pancreatic diseases are usually hardly governable; special problems are arosen with the treatment of pancreatic fluid collections. The focal pericystic pancreatitis, the reactive inflammation developing in the course of the injury of the gland as well as draining pancreatic duct filling the cyst up may result in pitfalls. Thus subcutaneous administration of Sandostatin was added to the usual therapeutic regimen in 12 patients. It was applied with external and internal drainage of pseudocysts in 10 patients and in one of them the complication was reduced in an unsuccessful attempt, respectively. The pseudocyst of one patient disappeared by sole somatostatin administration. One cystic formation did not respond to this kind of treatment thus a drainage procedure had to be performed. Based on our initial experiences we seem to find a rather promising tool that may influence the basic process beneficially and makes our instrumental interventions safer and more successful. PMID- 8367150 TI - [Successful surgical management of arterio-mesenterial duodenal compression]. AB - A 17 year old female patient developed in 6 month a gradually exacerbating stomach passage disturbance not responding to conservative treatment. Clinical and radiological examinations verified that the compression of the duodenum was caused by irregular position of the arteria mesenterica superior. The patient was operated on and a dissection and transposition of the duodenum was performed using an end-to-end anastomosis before the arteria mesenterica superior. This method has never been seen in Hungary before. The good result of the operation was verified by the control examinations. PMID- 8367151 TI - [Wound suturing at the turn of the century]. PMID- 8367152 TI - [Psychiatric description of erotomania and its forensic psychiatric assessment in the last third of the 19th century]. PMID- 8367153 TI - Oncology Nursing Society. PMID- 8367154 TI - Annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. Minneapolis, Minnesota, October 2-6, 1993. Abstracts. PMID- 8367156 TI - Reevaluating Act 111's insurance requirement. PMID- 8367155 TI - Managing wastes in Pennsylvania. PMID- 8367157 TI - Burden of proof remains for KEPRO. PMID- 8367158 TI - Alerting patients to the risk of radon. AB - The potential lung cancer risk from exposure to radon gas and the development of appropriate public health policy have been the subject of much discussion for several years. The American Lung Association has taken a leading role in educating the public on radon and other environmental hazards. This article presents background on radon, including the issues of risk assessment and policy development; reviews the current understanding of the hazards of exposure and the scope of the problem; describes how to test for radon; and discusses how to decrease radon levels. PMID- 8367159 TI - Think recycled. PMID- 8367160 TI - Improving quality, controlling costs: the role of managed care. Pennsylvania Medical Society Council on Medical Economics. AB - Recognizing the importance of managed care concepts in the nationwide debate on health system reform, the State Society's Council on Medical Economics has compiled a discussion draft of the Society's positions on "The Role of Managed Care in Improving Quality and Controlling Health Expenditures," excerpted here. In addition to members' comments, the Society is soliciting comments from health caregivers, legislators, regulators, labor, business, insurers, and most importantly patients. Members may obtain a free copy of the complete draft by calling the Society's Department of Media Relations at (800) 228-7823. Direct any written comments to the Society's Division of Communications and Public Affairs. PMID- 8367162 TI - Where is that missing element? PMID- 8367161 TI - Secretary proposes DOH restructuring. PMID- 8367163 TI - Helping the medically indigent and underserved. Part III--Recruiting physicians for medically underserved communities. PMID- 8367165 TI - Helping patients improve their physical fitness. Interview by Juli C. McGreevy. PMID- 8367164 TI - Establishing criteria for evaluating health system reform proposals. AB - Effective proposals for health system reform will need to address the many complex issues facing medicine. Piecemeal approaches to health system reform are not likely to succeed. The Health System Reform Index may be a useful instrument for evaluating the scope and potential success of proposals that address critical issues in health care. PMID- 8367166 TI - Commentary: HIV-infected physicians--who has a right to know? PMID- 8367167 TI - Leaders discuss roles, future of medicine. PMID- 8367169 TI - Pennsylvania Medical Society Membership Directory, 1993-1994. PMID- 8367168 TI - The federation needs you! PMID- 8367170 TI - Reaching out to our nursing colleagues in the former USSR: a review of recent cross-cultural experiences. PMID- 8367171 TI - Total quality improvement (TQI). PMID- 8367172 TI - HIV/AIDS update. PA regional HIV planning coalitions. PMID- 8367173 TI - Nurse entrepreneur/intrapreneur corner. PMID- 8367174 TI - [HIV infection in childhood]. AB - The increasing heterosexual transmission of HIV leads to an increase of vertical HIV-infection from mother to child. In Austria 19 children below 13 years with AIDS are registered, 16 of them had been infected by their mothers (osterreichische AIDS-Statistik, January 29, 1993). Clinical manifestations of HIV-infection in infants and children are different from those in adults. In this article we describe the typical signs like severe recurrent bacterial infections, failure to thrive, lymphoid interstitial pneumonia and neurologic symptoms as developmental delay, loss of previous acquired skills and progressive motor abnormalities. The difficulties of the diagnosis of HIV-infection in an infant born to a seropositive mother and problems with the integration of HIV-infected children in kindergarten and school are discussed. PMID- 8367176 TI - [Recommendations for treatment of acne vulgaris]. AB - Acne vulgaris is by far the most prevalent of adolescent skin disease, involving 60-80% of the teenage population. By androgen-stimulation the production of sebum is increased and by hyperkeratinisation the canal of the pilosebaceous follicle will be closed, thereby causing formation of comedones. These will get infected with Propionibacterium acnes. The treatment of acne vulgaris therefore consists in 4 steps: sebosuppression (with Benzoylperoxid), keratolysis (with Vitamin A acid and Azelainacid), bakteriostasis and stopping inflammation (with antibiotics). A mild cure of the affected skin is necessary too. PMID- 8367175 TI - [Psychological disorders in children and adolescents]. AB - After some introductory remarks on definition and frequency, a classification of psychiatric disorders in children and adolescents is given. Due to limited space, the various disorders are discussed only in terms of their relation to phases of development in childhood and adolescence. Finally, a sketch of basic ideas of etiology and the most important therapeutic approaches is presented. PMID- 8367177 TI - [Interdisciplinary team work in the treatment of cystic fibrosis: a model of psychosomatic cooperation]. AB - The "team-approach" in the care of chronically ill children is one way of interdisciplinary cooperation. The care of CF-patients requires the coordination of all treatment-measures and the integration of psychosocial counselling and management into medical treatment. Not only emotionally straining situations- "telling" the diagnosis, non-compliance, care of terminally ill patients--have to be managed, but both, illness and treatment, produce a lot of problems, to which solutions have to be offered. The task of psychological staff is on the one hand to contribute their specific knowledge to treatment-concepts, to enhance the psychosocial competence of the medical staff and, on the other hand, to offer counselling to the patients and their parents. PMID- 8367178 TI - [N-acetyl-beta-glucosaminidase (beta-NAG) in urine: a parameter for early detection of diabetogenic nephropathy in childhood]. AB - N-Acetyl-beta-D-glucosaminidase (NAG) can be found in kidney in high activity. By determination of this enzyme activity in urine nephropathies can be recognized reliably. We have measured this lysosomal enzyme in the urine (Colorimetric method by Noto) of 206 children suffering from diabetes mellitus to find out whether diabetic nephropathy can be detected as soon as possible. Additional beta 2-microglobulin (ELISA) was measured in urine, which is reabsorbed nearly complete in the tubulus. The several proteins in urine were identified by SDS PAGE. A high excretion of beta-NAG was found in children and adolescents with a poor metabolic control (elevated HbA1c). There was no correlation between NAG activity, duration of the diabetes and the age of the children. An elevated excretion of beta-2-microglobuline could be found only in seven children with a duration of the diabetes about six years; their HbA1c levels were high. The SDS PAGE showed a pattern of glomerular protein excretion according to the duration of the diabetes. However there was no significant correlation to the metabolic control. Only in four children we ascertained mixed proteinuria. The increasing levels of urinary NAG may represent the increasing severity of nephrotic damage by diabetes. The estimation of NAG levels in urine would seem to be reliable in the early detection of diabetic angiopathy also and may serve as an index of diabetic control independent of blood sugar levels. PMID- 8367179 TI - [Pediatric Research in Central Europe. Vienna, 18 June 1993. Abstracts]. PMID- 8367180 TI - Wheelchair selection. AB - Selection of an appropriate wheelchair is an essential part of discharge planning. Although the physical therapist plays the primary role in wheelchair recommendations, all those involved in patient care need to have a basic understanding of factors that are considered. This article discusses these factors, which include patient diagnosis, prognosis, medical status, functional status, mental status, environment, and funding. It also emphasizes that the decision-making process is a team effort and that the patient and his/her family are key members of that team. Basic terminology, wheelchair components, and available options for wheelchairs and wheelchair cushions are addressed. PMID- 8367181 TI - Development of an orthopaedic case manager role. AB - Creation of a case manager role was one institution's strategy to improve the coordination and delivery of care for orthopaedic trauma patients. This article describes the development and implementation of the innovative role within a large county health system and applies Neuman's Health Care Systems Model to the process. PMID- 8367183 TI - From the president: health care reform--what you can do. PMID- 8367182 TI - Avascular necrosis of the bone: the causes and the cures. AB - Injury to bone directly or indirectly influenced by the pathophysiologic effects of ischemia or various disease processes can have sensitive and dramatic effects upon intraosseous microvascular structures. The femoral head is a common area affected by avascular necrosis. The causes, cures, and staging management of this microcirculatory phenomenon will be presented. PMID- 8367184 TI - An assessment of discharge planning models: communication in referrals for home care. AB - A home care referral generated upon hospital discharge communicates essential patient care information, links service providers, and facilitates continuity of patient care. The literature however, reveals that communication efforts are often inadequate and may even fail in this system. The purpose of this research was to examine whether various discharge planning models employed by hospitals resulted in differences in the quantity and quality of communication about patients referred for home health care. Kelly and McClelland's (1985) typology of discharge planning models provided the framework for the study. Using instruments designed specifically for this project, six referring hospitals' functional discharge planning models were labeled and 300 closed home care records of referrals were reviewed to ascertain the amount and type of data transmitted. Results indicated that only slightly more than half of the data recommended by the literature was actually transferred and that data was primarily background in nature. The hospital discharge planning model did make a significant difference in the amount and type of data shared, with liaison nurses sending the greatest amount of data. However, both conceptually and in practice, the discharge planning models simply describe an allocation of responsibility among various health personnel. They are not operational models in the traditional sense. PMID- 8367186 TI - Antigout medications. PMID- 8367185 TI - Sacred cows. PMID- 8367187 TI - Deep venous thrombosis. PMID- 8367188 TI - Respect for persons: the patient with AIDS. AB - Even though the Code for Nurses calls for nurses to provide nondiscriminatory care and to treat patients with respect, research shows that nurses (1) are reluctant to provide care to and (2) believe that they should have the right to refuse to care for patients with AIDS. This article presents two contrasting situations and focuses on the ethical principle of respect for persons. Nurses need to examine their own practice to determine if they are providing care that respects the uniqueness and rights of their patients. PMID- 8367189 TI - Clinicopathological features of xanthogranulomatous pyelonephritis in infancy. AB - Xanthogranulomatous pyelonephritis (XGP) is an unusual chronic inflammatory condition which most often affects women in their 5th to 7th decades and is rare in infants. Predisposing factors include infection, calculi and obstructive uropathy. We have reviewed the surgical files of 4 cases seen over a 28 yr period from 1964-91. All of the 3 partial and one total nephrectomy specimens demonstrated typical features of XGP with renal parenchyma effaced by a mixed acute and chronic inflammatory infiltrate which included prominent aggregates of foamy histiocytes containing eosinophilic inclusions. No Michaelis-Gutmann bodies were seen. This study shows the association of XGP with chronic infection, anatomical malformation and reflux in infancy, and raises the possibility of a temporary altered immune response in its pathogenesis. PMID- 8367190 TI - Ultrastructure of human melanosis coli with reference to its pathogenesis. AB - Colonic mucosal biopsies from patients with melanosis coli were examined by electron microscopy. They showed apoptosis of colonic surface epithelial cells and phagocytosis of resulting apoptotic bodies by intraepithelial macrophages. The latter migrated to the lamina propria where intracellular degradation of the apoptotic bodies resulted in formation of lipofuscin, characteristic of this condition. The results showed the pathogenesis of human melanosis coli was identical to that determined in an animal model of this disease. PMID- 8367191 TI - Test and teach. Number Seventy. Diagnosis: Transient myeloproliferative disorder in a child with Down's syndrome. PMID- 8367192 TI - Test and teach. Number Seventy-One. Diagnosis: Systemic lupus erythematosus (SLE) lymphadenitis (necrotizing lymphadenitis). PMID- 8367193 TI - Diagnosis of metastatic carcinoma of stomach using fine catheter aspiration cytology. AB - The value of fine catheter aspiration cytology organs of the peritoneal cavity in the diagnosis of a metastatic carcinoma is illustrated by this case report. The finding of unequivocal malignant cells was quite unexpected and led to an investigation of the gastrointestinal tract which demonstrated a primary carcinoma in the stomach. This was further confirmed on a biopsy of the tumor and cell block preparations of aspirated material on which immunostaining was done and which further substantiated the light microscopic cytohistologic diagnosis. The findings presented in this article further emphasize the value of fine catheter aspiration cytology in not only identifying tumor type or predicting the source of the primary but also in managing patients admitted with abdominal pain as an emergency who may be saved from an unnecessary laparotomy which would have otherwise been done for a diagnosis. PMID- 8367194 TI - DNA analysis and clinical outcome in pediatric adrenal cortical tumors. AB - Adrenal cortical neoplasms are uncommon and it is often difficult to separate benign tumors from those that are malignant. Histology does not provide a reliable guide, particularly in pediatric cases. It has been suggested that analysis of nuclear DNA content may complement conventional histopathologic methods in the diagnosis of malignancy. Six previously reported adrenal cortical tumors from children aged 6 mths to 6 yrs were analysed using a CAS 200 image analysis system which provided DNA histograms on each of the cases. In 5 cases a significant proportion of the tumors showed aneuploidy and in only one case did most of the tumor cells show a diploid pattern. All 6 cases were treated with surgery alone with long term survival and follow up of 2-15 yrs except in one child with a histologically benign aneuploid tumor who died post-operatively from measles pneumonia. No correlation between histological appearance, outcome and ploidy was seen. The aneuploid tumors included those classified by current histological methods as benign (1), indeterminant (2) and malignant (2). The one diploid tumor seen was a large tumor of indeterminant malignancy that did not recur. Although the series is quite small these observations suggest that abnormalities of DNA content may not provide an objective measure of the malignant potential of adrenal cortical tumors in children. PMID- 8367195 TI - Inhibition of the neutrophil respiratory burst by neoglycoalbumin. AB - Both human serum fraction V albumin subjected to enhanced glycation by incubation with glucose, and a highly glycated albumin fraction prepared by m-phenyl boronic acid agarose affinity chromatography, when compared with albumin preparations of lesser glycation but equal concentration, inhibited the respiratory burst of the human neutrophil. Native albumin also inhibited the respiratory burst in proportion to its concentration. It is suggested that the neoglycoalbumin impairs glucose utilization by the neutrophil. PMID- 8367196 TI - von Willebrand's disease: laboratory investigation using an improved functional assay for von Willebrand factor. AB - This report details extensive studies investigating an improved screening procedure for the laboratory confirmation of clinically suspected von Willebrand's disease (vWD). Over the past two years, over 400 plasma samples, comprising samples derived from both normal individuals (n = 112) and from patients undergoing investigation on clinical grounds, underwent analysis in this screening procedure, comprising three distinct assays: a standard ELISA assay for von Willebrand Factor (vWF) antigen levels (vWF:Ag), a standard ristocetin cofactor (R Cof) assay, and a functional collagen based ELISA assay for vWF ('CBA'). Normal individual plasma samples yielded normal reference values (mean +/- 2SD) approximating 50-200% (vWF:Ag, R Cof) or 50-250% (CBA). In order to permit comparative analysis, and based upon derived assay values, and subsequent multimer analysis, patient samples were either deemed to derive from persons unlikely to suffer vWD ('non-vWD' patient group) or those potentially suffering vWD. The latter group was further separated into subgroups based upon the likelihood, and probable subtype of vWD. In conjunction with the vWF:Ag assay, the CBA provides the basis by which an effective predictor system (likelihood and probable subtype of vWD) can be offered on the basis of preliminary screening procedures. To date, there has been no overlap in vWF:Ag to CBA ratios (vWF:CBA) between patients yielding Type II vWD like multimer patterns and those yielding Type I vWD, or normal, multimer patterns. Thus, high vWF:CBA (i.e. > or = 3.0) would suggest a Type II, or pseudo, -vWD like defect, whereas low vWF:CBA (< or = 2.5) would likely derive from either normal individuals, or persons suffering from Type I vWD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367197 TI - Immune events in lymphoid tissues during experimental glomerulonephritis. AB - To investigate immune events within lymphoid tissues and their role in relation to glomerular disease, systemic lymphoid tissues from rats with accelerated experimental anti-GBM glomerulonephritis or with primed serum sickness glomerulopathy were studied. Following disease induction, changes in leukocytic populations within lymphoid tissues were analysed over a 28 day time course by immunoperoxidase labelling with monoclonal antibodies. In anti-GBM glomerulonephritis there was rapid and severe renal injury and pulmonary hemorrhage (Good-pasture's syndrome). In these rats, antigen (rabbit IgG) was deposited on the GBM and within germinal centres of lymphoid tissues. From day 3 onwards, there was a significant increase in the number of T cells, presumably CD4+ T helper cells, present within enlarged germinal centres of kidney draining lymph nodes, axillary lymph nodes and spleen (p < 0.05) which peaked at day 14 (up to 28% of total cells) when there was intense deposition of rat IgG and C3 on the GBM. Similarly, increased numbers of ED1+ macrophages were evident in both germinal centres and T cell areas (paracortex and periarteriolar lymphoid sheath). Notably, the appearance of IL-2R expression in germinal centres and T cell areas was apparent from day 7 onwards. This was the time when widespread renal interstitial infiltration, cellular immune activation and severe renal functional and histological injury developed. In addition, antigen deposited in germinal centres was found to be associated with CD4+, CD5-, ED1- cells, most probably antigen presenting dendritic cells. In contrast, in acute serum sickness there was no antigen deposited in germinal centres and only mild renal injury and minor changes within lymphoid tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367198 TI - Dual CD45RA, CD45RO positive T-lymphocytes within rheumatoid arthritic joints. AB - This report documents the presence of an expanded population of dual CD45RA, CD45RO positive T cells (up to 91% of T cells) in the rheumatoid joint. Cells from peripheral blood (PB) and synovial fluid (SF) were analysed by dual immunofluorescence labelling. Synovium from a separate patient population was analysed by single and dual immunoenzyme staining of serial sections. Dual CD45RA, CD45RO positive T cells were found in PB (up to 74%), SF (up to 91%) and synovium. This was associated with a lack of early activation antigens (4F2, interleukin-2 receptor, transferrin receptor) but increased HLA-Class II antigens (HLA-DR, -DP, -DQ) in SF compared with PB. This intermediate activation phenotype may support the hypothesis that T cell activation or reactivation occurs within the rheumatoid joint. PMID- 8367199 TI - Susceptibility of Legionella species to antimicrobial agents. AB - Thirty-five clinical isolates of Legionella species were tested against 7 antimicrobial agents using an agar dilution technique. Results obtained on charcoal-supplemented (BCYE) and charcoal-free agar (BSYE) were compared. On BCYE, the most active agent was rifampicin; the minimal inhibitory concentration inhibiting 90% of the strains (MIC90) was 0.008 mg/L. Imipenem was the next most active in vitro (MIC90 0.06 mg/L). The macrolide antibiotics and ciprofloxacin also inhibited the organisms at low concentrations (MIC90 < or = 2 mg/L). In general, MIC's obtained on BCYE agar were at least twofold higher than on BSYE agar except for that of imipenem. BSYE agar is a suitable alternative medium for susceptibility testing of most Legionella species. Erythromycin and rifampicin continue to demonstrate good in vitro activity against legionellae in Australia. On the basis of in vitro susceptibility tests, the other macrolides and ciprofloxacin are likely to be suitable alternatives for the treatment of legionellosis. PMID- 8367200 TI - Squamous cell carcinoma arising in an eccrine hidrocystoma. AB - This report describes the case of a 63 yr old male with an enlarging lesion on the left cheek. Excision biopsy showed a squamous cell carcinoma arising from an eccrine hidrocystoma. The eccrine hidrocystoma showed foci of squamous metaplasia and the sequence of squamous metaplasia complicated by squamous carcinoma is postulated. Squamous differentiation in eccrine neoplasia is discussed. PMID- 8367201 TI - Two fatal infections in immunocompromised patients caused by Scedosporium inflatum. AB - Two fatal infections caused by Scedosporium inflatum in immunocompromised patients are described. One patient developed peritonitis with this fungus 3 mths post renal transplantation. After a stormy course in the intensive care unit he eventually died. The other patient was suffering from non-Hodgkin's lymphoma and showed persistent neutropenia. Progressive deterioration occurred, and disseminated fungal infection was found at post mortem. Both isolates were resistant to all commonly available antifungal agents. PMID- 8367202 TI - Metastatic osteogenic sarcoma to the heart presenting as bacterial endocarditis. AB - A patient with metastatic osteogenic sarcoma involving the left atrium is described who presented with features of bacterial endocarditis. The source of infection was the adjacent esophagus into which the tumor had eroded. This case demonstrates that sarcomas metastasizing to the heart may result in a clinical condition indistinguishable from infective endocarditis. At post-mortem, careful dissection of cardiac metastases should be undertaken to check for possible esophageal involvement. PMID- 8367203 TI - Fibro-osseous pseudotumor of the digits: report of a case with immunohistochemical and ultrastructural studies. AB - A polypoid fibro-osseous nodule arising from the soft tissues of a toe of a 17 yr old man is described. Initial partial excision of the nodule led to a wrong diagnosis of pyogenic granuloma. The mistaken diagnosis was based on finding an extensively ulcerated polypoid nodule with a core of fibrovascular tissue which resembled granulation tissue. The fast growing lesion recurred twice within 4 mths following incomplete excisions. Bony destruction of the distal phalanx was noted radiologically at the second recurrence. The rare lesion is an example of fibro-osseous pseudotumor of the digits, sometimes described as pseudomalignant osseous tumor of the soft tissues. It is curable by complete local resection. The importance of recognizing this lesion lies in its potential to be confused with parosteal or extraskeletal osteosarcoma. The fast growth rate of present case led to a strong clinical suspicion of malignancy. Incomplete excisions resulted in local recurrences rendering more extensive surgery necessary. There was no further recurrence 12 mths after the last excision. PMID- 8367205 TI - Leiomyosarcoma of the thyroid: immunohistochemical and ultrastructural study. AB - A primary leiomyosarcoma of the thyroid was seen in a 54 yr old female. The patient had a solitary, cold nodule with no abnormalities of thyroid function tests. Histologically it was composed of characteristic interlacing fascicles of spindle cells which, electron microscopically, showed thin myofilaments with focal dense bodies. Immunohistochemistry showed a strong reaction with vimentin, smooth muscle actin and desmin. No epithelial differentiation was noted immunohistochemically or ultrastructurally. No tumor recurrence was detected 15 mths after surgery. It is postulated that the smooth muscle differentiation had arisen by metaplastic change or de-differentiation with re-differentiation of anaplastic thyroid carcinoma. PMID- 8367204 TI - Intra-abdominal desmoplastic small round cell tumor. AB - A rarely encountered but distinctive type of aggressive malignant tumor of childhood and adolescence has been recently described as occurring predominantly or exclusively intrabdominally. It is characterized by a generally diffuse pattern of growth of small cells with hyperchromatic nuclei, scanty cytoplasm, patchy epithelial differentiation, immunohistochemical co-expression of keratin and desmin intermediate filaments and a focal but pronounced desmoplastic stromal component. It is regarded as yet another variant in the group of small round cell tumors (SRCT) of infancy and childhood. This case report of a mass in the greater omentum of a 15 yr-old girl adds to the 33 cases already described in the English literature. PMID- 8367206 TI - Comparison of cytogenetic findings after fibroblast culture and whole tissue cryopreservation. PMID- 8367207 TI - Extrapulmonary tuberculosis--two case reports with fatal outcome. PMID- 8367208 TI - [Odontogenic cysts--histogenesis, histology, potential for possible neoplastic transformation]. AB - Epithelial odontogenic cyst develop either in result od peridental inflammation radicular cyst, or in result of developmental disturbances in the course of the odontogenesis. The latter are divided into primordial and dentigerous cysts. Some odontogenic cysts are lined with squamous keratotic epithelium -ortho- or parakeratotic type. The latter is characterized by higher recurrence rate and malignant potential. Primary intraosseous carcinoma (PIOC) both keratizing and nonkeratizing might originate in keratocyst. Mucoepidermoid carcinoma and occasionally other benign and malignant sialogenic tumors might originate in keratocyst either. In addition in the jaw-bones with the odontogenic cyst or even without the cyst, squamous odontogenic tumor (SOT) can develop or so-called squamous odontogenic tumor-like proliferation in odontogenic cyst (SOT-LPOC). PIOC is a cancer of low grade malignant potential. Biology of SOT and SOT-LPOC in not elucidated yet as these are not frequently occurred lesion. PMID- 8367209 TI - Hypothalamic and neurohypophysial vasopressin and oxytocin content as influenced by haemorrhage in melatonin-treated male rats. AB - The effect of haemorrhage (1 ml per 100 g b. w.) on the vasopressin and oxytocin storage in the hypothalamus and neurohypophysis of melatonin-treated male rats was determined. Melatonin treatment (100 micrograms/100 g b. w., once daily over 8 days) resulted in a known decrease of vasopressin as well as oxytocin content both in the hypothalamus and neurohypophysis. Haemorrhage decreased the neurohypophysial vasopressin and oxytocin storage in animals injected with vehicle solution or otherwise not treated. In melatonin-treated rats, however, bleeding did not affect the actual (i.e., decreased by melatonin) vasopressin and oxytocin content in the hypothalamo-neurohypophysial system. The results demonstrate that melatonin may be involved in mechanisms determining the rate of the response of vasopressinergic and oxytocinergic neurones to bleeding. PMID- 8367210 TI - The effect of haemorrhage and melatonin on neurohypophysial vasopressin and oxytocin content in pinealectomized male rats. AB - The effect of haemorrhage and melatonin on the vasopressin and oxytocin storage in the neurohypophysis of pinealectomized male rats was determined. Sham operated or pinealectomized rats as well as rats pinealectomized and injected with melatonin (100 micrograms/100 g b. w., once daily over 8 days) or with melatonin vehicle (2.2% ethanol in 0.9% NaCl) were subsequently subjected to haemorrhage. Pinealectomy was followed by known decrease of both vasopressin and oxytocin content in the neurohypophysis as compared to sham operated rats. Similarly, haemorrhage decreased the neurohypophysial vasopressin and oxytocin storage in both sham operated and pinealectomized animals. Melatonin, injected to pinealectomized animals, did not modify the diminution of neurohypophysial vasopressin and oxytocin content caused by bleeding. The results demonstrate that in pinealectomized rats melatonin does not affect the rate of the response of vasopressinergic and oxytocinergic neurones to bleeding. PMID- 8367211 TI - Immunocytochemical analysis of cellular infiltrates in primary glial and metastatic tumors in human brain. AB - Forty eight human brain tumors: 31 primary glial tumors and 17 metastasizing neoplasms were submitted for an immunocytochemical characterization of mononuclear cell infiltrates in tumor tissue and in its surroundings, with antibodies CD 68, CD45RO, UHCL1, EMB11, CD21 and OPD4. It was found that cells were mainly marked with CD68 and CD45RO, UHCL1. The counting of the marked and unmarked mononuclear cells proved that there is a high degree of variability in cell density which is tumor type and case depended. The results indicate that there were fewer cells which reacted to the antibody EMB11 as compared with cells marked with other antibodies. With CD21 and OPD4 only single cells were marked. A great number of cells remained unmarked. There was a significant difference between the primary glial and the metastatic tumors as far as the number of marked cells is concerned. It is suggested that the difference between primary and metastatic tumors in the number of mononuclear cell infiltrates can be connected with a possibility that the metastatic tumor will present its antigenicity easier as compared with primary tumors of glial origin. PMID- 8367212 TI - Photodynamic therapy of transplantable interstitioma testis in Wistar rats; histopathological examination after Evans blue injections. AB - The following examination was carried out confirm the effect of Photodynamic Therapy on tumor damage induction in Wistar rats. 20 male Wistar rats bearing interstitioma testis with mean diameter of 2 cm were treated with Photodynamic Therapy, i.e. injected intravenously with alkaline solution of meta-tetra hydroxyphenyl-porphyrin in dose of 5 mg/kg of body weight and after 24 hrs the tumors were irradiated with red light (650 nm). 2 hrs later these rats were injected intravenously with dye, i.e. 1% solution of Evans Blue in volume of 5 ml per one rat. After next 2 hrs animals were sacrificed. Necrosis areas in tumors were evaluated both on routine paraffin embedded sections without Evans Blue injections, stained with HE only and on paraffin sections from sample containing dye alone. There was the significant increase in necrosis size in treated tumors in comparison to untreated controls or tumors that were given photosensitizer, i.e. porphyrin or light alone. Present data indicate positive role of Photodynamic Therapy on interstitioma testis necrosis induction in Wistar rats. PMID- 8367213 TI - Studies on teratospermatogenesis occurrence in man. AB - In 462 left testes of males, died in the age of 17-91 years (x = 51,9 +/- 16,8 years) the occurrence frequency and the degree of teratospermatogenesis activity was assessed. In the whole material, the phenomenon occurred in 84% of cases. In 47,83% of cases the grade of intensity was low (+), in 22% high ( ), in 14% moderate (++). Alcoholic intoxication occurred to have the heaviest impact on teratospermatogenesis frequency (92,5%); in liver cirrhosis the occurrence frequency was significantly more rare (76%). The age of cadavers and the weight of the gonad did not correlate with teratospermatogenesis occurrence frequency. Postmortem autolysis was not connected with the phenomenon occurrence also. It correlated positively albeit with type II and III seminiferous tubules, i.e. with tubules, where spermatogenesis was stopped on the stage of spermatids and spermatocytes, and negatively with hyalinized tubules, and also with the V% value of tubular membranes. PMID- 8367214 TI - Ultrastructure of diffuse malignant mesothelioma of the pleura. An analysis of ten cases. AB - An electron-microscopic examination of ten cases of malignant pleural mesothelioma is presented. The most characteristic features for diagnosis are: presence of microvilli and desmosomes, abundant intermediate filaments and direct contact between microvilli and collagen fibres. Microvilli were present not only on the luminal surface of the cells, but also on the abluminal surfaces. Differentiation towards the cells characteristic for rhabdomyosarcoma was found in one case. PMID- 8367215 TI - Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model. AB - In order to evaluate further the physiological and inflammatory changes of meconium aspiration syndrome (MAS), 25 newborn piglets (1-2 days old, 1.5 +/- 0.4 kg) were studied. Piglets were briefly ventilated with 100% oxygen and then received an intratracheal bolus of 3 mL/kg of a 20% suspension of human meconium. They were then further ventilated, keeping PaCO2 at approximately 40 torr and PaCO2 at 70 torr during 4, 12, 24, and 48 h studies. Pulmonary function studies and tracheal aspirates were obtained at time zero and serially throughout the study. Bronchoalveolar lavage was performed at the end of the study to examine endogenous surfactant function. Control piglets received 3 mL/kg of intratracheal saline and were then ventilated for 48 h at an inspired oxygen concentration and mean airway pressure matched to the meconium treated group (to control for the effects of hyperoxia and barotrauma on the lung). MAS caused acute decreases in gas exchange and dynamic lung compliance, which returned toward baseline by 48 h (P < 0.001, ANOVA). Tracheal aspirate absolute neutrophil count, neutrophil chemotactic activity, albumin, and total protein concentrations also increased significantly over time (P < 0.001). Endogenous surfactant function appeared to be significantly inhibited by the meconium. All variables of lung injury were significantly higher in the meconium group compared to the saline control group over the 48 h study. Newborn piglets provide a clinically relevant model of MAS, demonstrating physiological and inflammatory changes with apparent alterations in endogenous surfactant function. Effective therapies for MAS may require interventions directed at all of these components of lung injury. PMID- 8367216 TI - A simplified method for determining the frequency response of pneumotachographs used in infants. AB - In all rapidly changing systems, an appropriate response time of all sensing devices is essential for the accurate conversion of a physiological parameters to a proportional electrical signal. The frequency response of equipment is the ability to accurately reflect both the magnitude and temporal relationship of dynamic events over a defined frequency range. The phase lag expresses the temporal delay between the physical event being measured and the output signal. The attenuation expresses diminution of the amplitude ratio of the output signal in relation to the input signal over a range of frequencies. We have developed a method that specifically addresses the measurement of frequency response and attenuation of pneumotachographs and low pressure transducers. The system consists of a 81 liter rectangular box separated in the middle by a 30.5 cm acoustic loudspeaker, the cone sealed by latex, and driven by a signal generator coupled to a low frequency amplifier. This system can produce an undistorted sinusoidal signal between 0 and 20 Hz, and the peak flow through the pneumotachograph is only minimally affected by changes in frequency. Rapid analysis is possible using an oscilloscope to produce Lissajou loops. There is no measurable attenuation between the electrical signal and the pressure generated over frequencies from 1 to 20 Hz. The system is accurate at low frequencies and can generate appropriate signals over the frequency range of interest for respiratory applications, and it can be inexpensively constructed. PMID- 8367217 TI - Predictive value of measurements of respiratory mechanics in preterm infants with HMD. AB - Conventional methods for measuring respiratory mechanics model the respiratory system as a single compartment. The interrupter technique allows the respiratory system to be considered as a two compartment model with "flow resistance" of the conducting airways (Rinit), calculated from the initial pressure drop (Pinit), considered separately from Pdiff, as a measure of the viscoelastic properties of the lung and chest wall and any pendelluft present. The pulmonary mechanics of 50 intubated and mechanically ventilated preterm infants (< or = 1500 g) were studied during the first week of life using conventional methods and the interrupter technique to determine whether it was possible to predict which infants would develop bronchopulmonary dysplasia (BPD). Pulmonary mechanics of preterm infants intubated and ventilated for apnea of prematurity were also studied. The dynamic compliance of the respiratory system (Crsdyn) was significantly lower on day 1 (P < 0.001) and during the first week of life in the infants with HMD who developed BPD (ANOVA, P < 0.0001). There was no significant difference in the respiratory system resistance (Rrs), Rinit, or Pdiff between BPD and no-BPD groups. However, Pdiff was significantly higher in infants with HMD, regardless of the outcome, when compared to the infants ventilated for apnea of prematurity. This suggests that the pathology of HMD is distal to the conducting airways and significantly alters the viscoelastic properties of the lung on day 1. Using stepwise logistic regression Crsdyn on day 1 and birth weight or gestational age were significant independent predictors or the development of BPD, correctly classifying 92% of infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367218 TI - Polysomnography in obese children with a history of sleep-associated breathing disorders. AB - We hypothesized that obese children with a history of breathing difficulty during sleep would demonstrate (1) evidence of complete and partial obstructive sleep apnea (OSA) with hypercarbia and/or hypoxemia; and (2) correlation between symptoms, degree of obesity, adenoid and tonsil size, and polysomnography (PSG) results. We evaluated 32 obese children [% ideal body weight (IBW), 196 +/- 45%] with a sleep history questionnaire, airway radiographs, electrocardiograms (ECG), and PSG. By history, we found snoring (100%), difficulty breathing (59%), sweating (44%), restlessness (53%), arousals (41%), apnea (50%), worsening with upper respiratory infection (URI) (81%), hypersomnolence (59%), and mouth breathing (59%). We found adenoid and/or tonsil enlargement on 75% of airway x ray pictures. ECGs were abnormal in 5 patients. Among all patients, mean sleep study oxyhemoglobin saturation (SaO2) was 85 +/- 16% and mean end-tidal CO2 (PetCO2) was 51 +/- 7 torr; 84% had paradoxical inward movement of the chest on inspiration, 59% had OSA, and 66% had partial OSA. In those with > or = 200% IBW and adenotonsillar enlargement, elevated PetCO2 and the presence of hypoxemia (SaO2 < 90%) for > or = 5% of the total sleep time (TST) were correlated, unlike in patients of similar weight but without adenotonsillar enlargement. Individuals symptoms did not correlate with the severity of PSG abnormalities. By discriminant analysis, using three variables (IBW, presence of adenotonsillar tissue, and presence of > or = 5 symptoms), we could predict PSG abnormalities with up to 81% reliability. Our findings indicate that in obese children, particularly those with %IBW > or = 200 and adenotonsillar hypertrophy, with sleep-disordered breathing evaluation by polysomnography should be considered. PMID- 8367219 TI - Effect of obesity on pulmonary function in children. AB - The effect of obesity on pulmonary function was studied in 13 children, aged 8-15 years, with 147-300% ideal body weight (IBW). Measurements included lung volumes, airflow rates pre- and post-bronchodilator nebulization, diffusing capacity (DLCO), maximal voluntary ventilation (MVV), minute ventilation VE), and resting energy expenditure (REE). When compared with predicted normal values for sex, height, and body surface area (BSA), decreases (mean % predicted, +/- SE) were observed in expiratory reserve volume (ERV, 36 +/- 5); forced expiratory volume in 1 second (FEV1, 73 +/- 5); forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%, 70 +/- 6); DLCO, absolute (52 +/- 3) and corrected (DLCO/VA, 71 +/- 5); and MVV (62 +/- 5). Residual volume (RV), RV/total lung capacity (TLC), VE, and REE were elevated. Other lung volumes were normal. Thus, obese children have altered pulmonary function, which is characterized by reductions in DLCO and ventilatory muscle endurance and airway narrowing. These alterations may reflect extrinsic mechanical compression on the lung and thorax, and/or intrinsic changes within the lung. The reduced DLCO may result from decreases in alveolar surface area relative to lung volume. PMID- 8367220 TI - Bronchoscopic diagnosis of an unusual presentation of pulmonary actinomycosis. PMID- 8367221 TI - Chronic modifications of lung and heart development in glucocorticoid-treated newborn rats exposed to hyperoxia or room air. AB - We assessed the mechanics and morphology of the lung in 165 rats treated neonatally with either room air (RA), O2, RA + steroids, or O2 + steroids. Newborn Sprague-Dawley male rats were randomly assigned to these groups. O2 exposure (0.96-1.0 FiO2) lasted 5 days, and dexamethasone treatment consisted of eight daily S.C. injections of drug or buffer in successive doses of 0.5, 0.4, 0.3, 0.2, 0.1, 0.1, 0.1, and 0.1 mg/kg. At 58 days, right ventricular systolic pressure (RVP) was measured. At 60 days, all rats were sacrificed for obtaining lung weight and DNA, saline pressure-volume (P-V) curves, and morphometry. We weighted right ventricles (RV) and left ventricles + septa (LV). Hyperoxia alone did not, but steroid decreased survival rate to 79.4% (95.3% in RA rats, P < 0.02). Only 21 of 40 (52%) O2 + steroids rats survived, less than in both RA groups (P < 0.001). RV weight, RVP and muscularization of alveolar duct arteries were significantly increased in O2 vs. RA rats. In RA + steroids rats, weight of the LV was decreased but RV, RVP, and lung vasculature were not affected. These effects were additive in the O2 + steroid group. Wet lung weights and DNA were increased for RA + steroid rats over all others. O2 and steroids shifted the P-V curve to the left and O2 + steroids still further. Maximal lung volume increased significantly with RA + steroids and still further in O2 + steroids but not in O2 alone. O2 and steroids significantly increased the mean linear intercept and O2 + steroids even more so.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367222 TI - Chest wall motion before and during mechanical ventilation in children with neuromuscular disease. AB - Patients with neuromuscular disease can display paradoxic motion of the rib cage (RC) and abdomen (AB), which increases the work of breathing and predisposes to respiratory muscle fatigue. Long-term mechanical ventilation can reverse chronic hypercapnea and decrease the work of breathing in these patients. Changes in chest wall motion (CWM) that occur during mechanical ventilation have not been studied. We have assessed CWM using a calibrated respiratory inductive plethysmograph before and during mechanical ventilation in 5 children and young adults with neuromuscular disease and paradoxic breathing at rest. Asynchrony of CWM was quantitated by measuring the phase shift, theta, between RC and AB motion (0 degree = synchronous motion, 180 degrees = paradoxic motion). The volume contribution of the paradoxing compartment to tidal volume (PC/VT) was calculated. Before mechanical ventilation, mean +/- SEM VT was 122 +/- 17 mL, theta was 131 +/- 15 degrees C, and PC/VT was -27 +/- 6%. During mechanical ventilation, VT increased to 274 +/- 47 mL (P < 0.05), theta decreased to 41 +/- 14 degrees (P < 0.05), and PC/VT increased to +39 +/- 9% (P < 0.02). We conclude that mechanical ventilation improves RC/AB asynchrony and reverses the negative contribution to tidal volume of the paradoxing compartment in children and young adults with neuromuscular disease. This implies that mechanical ventilation assumes most or all the role of the respiratory pump in these patients, which provides a rationale for the use of chronic or nighttime ventilation in the treatment of respiratory muscle fatigue. Assessment of CWM may be useful in the determination of optimal ventilator settings in this population. PMID- 8367223 TI - Longitudinal evaluation of pulmonary function in infants and very young children with cystic fibrosis. AB - Thirty-two infants with cystic fibrosis (CF) had pulmonary function testing and chest radiographs at the time of diagnosis and on average 1 year later, when they had no acute respiratory symptoms. At diagnosis, 14 of 32 infants had respiratory symptoms (RESP) and 18 did not have respiratory symptoms (NRESP). There were no significant differences in age, weight, or length between the RESP and NRESP groups. At diagnosis, the RESP group had significantly lower forced expiratory flows compared to the NRESP group (41 +/- 32% vs. 98 +/- 48% predicted); however, there were no significant differences in functional residual capacity or chest radiographic scores. Between diagnosis and follow-up, the NRESP group had no significant change in pulmonary function but a decline in chest roentgenographic (CXR) scores (22 +/- 2 to 21 +/- 2). For infants in the RESP group, there were no significant changes in FRC or CXR score. Maximal expiratory flow at functional residual capacity (Vmax FRC) rose from diagnosis to 1 year follow-up (41 +/- 32% to 74 +/- 27% predicted; P < 0.002); however, at follow-up flows for the RESP group remained significantly lower than flows for the NRESP group (74% vs. 113% predicted; P < 0.0005). For the 32 infants with CF, there was significant correlation between percent predicted Vmax FRC at follow-up and at diagnosis (r = 0.47; P < 0.02). Those infants with lower percent predicted flows at diagnosis were more likely to have lower percent predicted flows 1 year later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367224 TI - Seasonality in suicide and economic growth. PMID- 8367225 TI - Application of Hick's law of response speed in Alzheimer and Parkinson diseases. AB - Reaction time in normal subjects is known to increase in a log-linear fashion relative to the number of alternative choices. However, this relationship (formalized as "Hick's law") has received limited investigation in populations with neurological cognitive impairment. The present study used timed sorting of standard playing cards to test Hick's law for 20 young control subjects, and 20 each of age-matched elderly subjects with Alzheimer disease, Parkinson disease, and no cognitive abnormalities. Although Parkinson patients were slowest in the simple tasks of dealing out the cards and sorting by color, Alzheimer patients showed the greatest slowing for the more cognitively complex conditions of sorting by suit and rank of the cards. The performance of all four groups followed Hick's law in displaying a significant linear relationship between response time and log2 of the number of choices. These findings suggest that, although limitations of information-processing speed in Alzheimer and Parkinson disease affected choice response time, there may be sparing of fundamental cognitive organization in these disorders. PMID- 8367226 TI - Children's understanding of facial expression of emotion: III. Adults' categorical and dimensional responses to children's drawings. AB - 49 adult subjects responded to 37 children's drawings of six emotions (happy, sad, angry, afraid, surprised, and disgusted) by naming the emotion depicted and by identifying the pleasantness and arousal status of each drawing. Various analyses indicated that assignment to categories could be predicted on the basis of ratings of pleasantness and arousal (the two key dimensions of a bipolar affect space). Data support the contention that emotional responses should not be assessed solely on the basis of literal accuracy but should rather be described in terms of their location in affect space. PMID- 8367227 TI - Mortality from suicide in follow-up studies of schizophrenics. PMID- 8367228 TI - Can short-range intentions predict physical activity participation. AB - This study examined the issue of proximity of intention in the physical activity domain by employing both short-range (2 and 3 days) and longer range (4 weeks) intentions in the prediction of participation in physical activity. Subjects were 42 undergraduate students who completed intention and physical activity assessments every class (Monday, Wednesday, and Friday) for six weeks and also a single assessment four weeks apart. Analysis indicated that short-range intention is a better predictor of physical activity than is the longer range intention; however, even the short-range intention-physical activity correlations were only of modest magnitude. Interpretation of the results focused on the potential nonvolitional nature of physical activity and the possible role of perceived behavioral control and behavioral expectation. PMID- 8367229 TI - An anatomical analysis of Aikido's second teaching: an investigation of Nikyo. AB - One of the strongest subduing techniques of the Martial Art Aikido is classified as Nikyo (Second-teaching). This investigation focused on examining this teaching with the intention of describing the anatomical tissues involved in the etiology of pain experienced with the application of this procedure. Particular focus was placed on the examination of a cadaver's arm musculature affected when this maneuver was applied precisely. PMID- 8367230 TI - Perception of social support and blood pressure in young men. AB - This study investigated the association between perceived social support, blood pressure, and heart rate during rest and stress. 29 men were selected from 184 students on the basis of having high and low perceived social support. During rest and two of the laboratory stressors, the low-support group had higher diastolic pressure than the high-support group. Systolic blood pressure and heart rate did not differ between the two groups during either rest or stress. The low support group was slightly older (24.8 yr.) than the high-support group (22.4 yr.), but the groups did not differ with respect to parental history of hypertension, body mass index, smoking, anxiety, anger inhibition, or environmental stress. PMID- 8367231 TI - Depressed mood and social perception: a cross-cultural replication. PMID- 8367232 TI - Effects of predictable and unpredictable auditory stimuli on selective attention. AB - 6 normal male and 10 normal female high school students completed two versions of the Stroop Color-Word Task in the presence of predictable and unpredictable auditory stimuli. Selective attention was hypothesized to be facilitated by predictable auditory stimuli and unaffected or hindered by unpredictable auditory stimuli. A one-factor repeated-measures analysis of variance showed selective attention was facilitated significantly by the predictable auditory stimuli on a paced version of the Stroop Color-Word Task. PMID- 8367233 TI - Does cigarette smoking increase sleep problems. AB - Cigarette smoking has been associated with delayed sleep onset and diminished sleep duration, primarily on the bases of responses to one-shot questionnaires. This study used a survey format of daily diaries to observe sleep quality. 29 smokers were matched for age, ethnicity, and gender with 29 nonsmokers. Both groups recorded information on cigarette, alcohol, caffeine consumption, daily stress, and sleep quality. While the results showed that smokers were more likely to experience poor sleep than nonsmokers, these data are difficult to interpret because smokers also used significantly greater amounts of alcohol and caffeine. PMID- 8367234 TI - A clock paradigm to study the relationship between expectancy and response force. AB - It has recently been demonstrated that the force used by subjects to press a response key depends on stimulation conditions such as stimulus intensity, fore period, etc. We performed an experiment in which response force and reaction time were measured as a function of expectancy. In contrast to the paradigms used so far, we manipulated expectancy without using warning stimuli by applying a so called "clock-paradigm." It enabled us to avoid the possible arousing effect of the warning stimulus. Both reaction time and response force depended on expectancy. The results suggest that response force was not affected by arousal or activation but was affected by preparatory state at the moment of making a response. PMID- 8367235 TI - Psychology of computer use: XXVIII: Effect of computer use on depth perception. AB - 30 computer users were tested first after work and then second both before and after periods of computer use. Subjects' depth perception ability was unaffected. PMID- 8367236 TI - Microgenetic process of perception of subjective contour using "self-sufficient" inducing pattern. AB - To investigate the operation of two figural cues of "alignment" and "incompletion" in the perception of subjective contour, the microgenetic process of perception of subjective contour was analyzed. Two inducing patterns were used, one with both "alignment" and "incompletion" cues and another with only an "alignment" cue. The latter was a simplified version of the "self-sufficient" pattern presented by Kanizsa in 1979 which induced no subjective contour under usual observation. These two patterns were tachistoscopically exposed for 10 to 70 msec., and four subjects rated the clarity of subjective contour on 240 trials. As a result, the rated clarity of subjective contour in the pattern with only an "alignment" cue showed a slight "inverted-U" function with a peak at 30 to 40 msec. as the duration of exposure increased, while that in the pattern with both cues increased monotonically. It was shown that, even in the "self sufficient" pattern which induces no subjective contour under usual observation, the processing toward perception of subjective contour was generated at the early stage of the microgenetic process. The results also agree with this author's previous finding that "alignment" is active earlier in the processing of subjective contour than is "incompletion." PMID- 8367237 TI - The deterrent effect of the death penalty in Canada. PMID- 8367238 TI - Aspirin (acetylsalicylic acid) effects on behavioral thermoregulation with microwave radiation. AB - Aspirin is a widely used over-the-counter drug in our society which has wide therapeutic value, yet not all of the behavioral side effects have been studied. Different doses of aspirin solutions were administered (ip) prior to fixed interval 2-min. schedules of microwave reinforcement in rats tested in a cold environment. Four Sprague-Dawley rats were conditioned to regulate their thermal environment with 5-sec. exposures of MW reinforcement. Friedman's nonparametric test showed significant differences among aspirin and saline-control doses. Post hoc sign tests showed that a moderate dose of aspirin increased operant behavior reinforced by MW radiation, yet lower and higher doses decreased and then increased the rate of responding which resulted in an inverted U-shaped trend. Possible multiple effects of aspirin in terms of its thermoregulatory as well as its pain-tolerance properties, and implications for hypothalamic "set point" are discussed. PMID- 8367239 TI - Extraversion-introversion and spatial intelligence. AB - The purpose of this study was to assess whether extraversion-introversion is related to spatial intelligence. First-year psychology students (58 men, 108 women) in an open-admission community college responded to a battery of black and white and color spatial ability tests, and the Eysenck Personality Inventory. As hypothesized, a small but significant relationship was found between scores on extraversion and on the SEK Test (colored spatial test). Gender differences in performance on the spatial tests favored males. Scores on three of the Spatial Dimensionality Tests correlated significantly with those on the SEK Test. Recommendations include investigating the effect of a variety of spatial problems in combination with other personality variables. PMID- 8367240 TI - Negative addiction in male and female runners and exercisers. AB - 72 male and 26 female runners and 60 male and 30 female exercisers were tested on the Negative Addiction Scale of Hailey and Bailey along with demographic questions to examine the relationships among gender, age, years of exercise experience, and addiction to exercise. Analysis showed no differences in addiction scores by age, gender, or type of activity. A trend showed longer involvement in physical activity was associated with higher addiction scores. PMID- 8367241 TI - Literacy and hemispheric specialization for language: dichotic listening in young functionally illiterate men. AB - The functional cerebral organization of young men who were defined as illiterate was studied by testing their dichotic listening for language stimuli. These functionally illiterate men showed greater right ear advantage for language stimuli than 50 educated subjects, a pattern already observed with completely illiterate persons of both sexes. This finding is consistent with the view that mastering written codes for language might be one of the most relevant parameters in hemispheric specialization when language is studied. PMID- 8367242 TI - Comparison of larger and smaller groups on a ward for physically handicapped children on interaction in the "present" game. AB - During a game the number of presents from 23 severely handicapped children during 10 15-min. interactions were compared. Children in groups of 6 to 12 interacted more with peers than those in groups of 19 to 24. Smaller groups seemed more facilitative of play. PMID- 8367243 TI - Laboratory sleep patterns and dream content of type A and B scoring college students. AB - The suggestion that there may be a discrepancy between subjective and objective measures of sleep led us to explore the sleep and dreams of 7 Type A and 7 Type B scorers in our laboratory over a three-night period. In earlier studies, Type A scorers had indicated that their sleep was somewhat more disturbed and their dream content generally more active and negative in tone than that of Type B scorers. However, in this study the only differences were that Type A scorers had a greater number of body movements and greater dream recall than did Type B scorers. These results seem to indicate that the impression Type A scorers have of the quality of their sleep and dreams may be a function of their waking life style. PMID- 8367244 TI - A test of Magill's closed-to-open continuum for skill development. AB - Magill's arrangement of Gentile's 2 x 2 matrix of skills classification into a closed-to-open-skill learning continuum was investigated. 63 volunteer university students were assigned to three experimental groups who performed different learning sequences on the Bachman Ladder for four practice sessions, climbing the unsupported Bachman Ladder (Task 4) in the final scored session. Following practice sessions, a five-trial, scored, Task 4 "retention" session was performed. Analysis of variance of retention trials indicated no difference between the practice groups regardless of practice sequence. Comparison of five selected trials from the Task 4 practice session and the five Task 4 retention performances, using a 4 x 2 analysis of variance with repeated measures, indicated significant group and time effects but no interaction. While Magill's arrangement of related activities into closed-to-open-skill learning continuums is supported, the specific arrangement of the lead-up skills does not appear critical. The question of task specificity for any learning continuum is raised, and further issues for research are proposed. PMID- 8367246 TI - Biomedical applications of hand-held force gauges: a bibliography. AB - Hand-held force gauges have been used increasingly in recent years to measure sensory and motor performance. In an effort to identify comprehensively journal articles in which the biomedical use of hand-held force gauges is described, five bibliographic data bases were searched, reference lists of relevant articles were examined, and current journals were scanned. The multifaceted process resulted in a bibliography of 158 articles describing the use of the instruments to measure muscle performance, resistant to joint movement, and force or pressure sensitivity. PMID- 8367245 TI - Cortisol, biochemical, and galvanic skin responses to music stimuli of different preference values by college students in biology and music. AB - The purpose of this study was to examine biochemical and galvanic skin responses to music stimuli. Specifically, 30 university biology and 30 music students' plasma levels of norepinephrine and cortisol and their galvanic skin responses were measured before and after listening to two different musical selections, one of which was preferred (liked) by the music students and not preferred (disliked) by the biology students. The music-listening sessions and the controlled silent sessions were done in an anechoic chamber. 30 biology majors and 30 music majors were in the experimental groups; 14 biology and 17 music majors comprised the control group. Analysis indicated that the cortisol levels and galvanic skin responses were significantly higher for the music majors than the biology majors. The data indicate that music majors listen more critically and analytically to music than biology majors, and cortisol levels are associated with this as increases in music majors and decreases in biology majors after the music. PMID- 8367247 TI - Including neither-type in the morningness-eveningness dimension decreases the robustness of the model. AB - The present paper is a study of axillary temperature and performance during the waking part of the day and the relationship of these two variables to Morningness Eveningness preferences. A reduced scale of the Horne and Ostberg questionnaire was adapted and standardized for the Spanish population, and 3 groups of subjects were formed (Morning-types: 3 men, 2 women; Neither-type: 3 men, 6 women; Evening types: 1 man, 4 women). Three different tasks were tested, auditory reaction time (to measure alertness and speed), index finger tapping (motor skill), and verbal memory (information processing). The subjects were tested hourly in 13 sessions spread out over the day. Morningness-Eveningness preference groups did not differ in temperature and performance. Neither-type subjects did not present values intermediate between those of the Morning- and Evening-types. PMID- 8367248 TI - Effects of elevating blood alcohol levels on tasks related to dart throwing. AB - Light (0.02% BAC) and moderate (0.05% BAC) does of alcohol were administered to 10 dart throwers while effects were monitored on tasks related to dart throwing, i.e., rotary pursuit and hand steadiness. Balance and accuracy of throwing improved with the 0.02% BAC, but performance was impaired with 0.05% BAC. The higher BAC levels were linked with deteriorations on rotary pursuit and hand steadiness. PMID- 8367250 TI - Priming effect in a color discrimination task. AB - Two experiments were run to test whether the automatic coding of colors generates priming effects. Subjects were tachistoscopically presented a series of prime target sequences. The prime stimulus could be either a red, green, or black circular dot, followed by a red or green annular ring (target). The role of automatic and conscious mechanisms was investigated in Exp. 1 by manipulating the predictive validity of the prime stimuli (80%, 50%, 20%), keeping constant the value of stimulus-onset asynchrony (350 msec.). Analysis showed priming effects even in the low predictive condition, where no conscious expectations could be activated. In Exp. 2, three different values of stimulus-onset asynchrony were used, 150, 350, and 2100 msec. Priming effects were obtained in the short and medium stimulus-onset asynchrony condition but not in the long one. Over-all, the data of both experiments produce converging evidence which indicates that the automatic elaboration of colored stimuli may produce priming effects. PMID- 8367249 TI - Authoritarian attitudes and aesthetic preferences: a Bulgarian replication. AB - This report describes a Bulgarian replication with 173 students of a German study concerning the effect of stimulus properties of complexity and order and authoritarian attitudes on the perceived pleasantness of polygons. Analyses of variance yielded neither significant main effects nor significant interactions for the different measures of authoritarianisms, but there were significant main effects for order and complexity. PMID- 8367251 TI - Self-efficacy and anxiety and their relationship to training and race performance. AB - The purpose of this study was to examine the validity of task-specific and general measures of physical self-efficacy in a competitive sports setting and how these measures relate to anxiety and actual running performance. 47 members of a running club and 16 members of a university track team completed measures assessing general and task-specific self-efficacy, anxiety, and training experience and were asked to run in three running events. Associations among these variables and running performance, examined by correlational and regression analyses, indicated that race finishing time was significantly related to a number of training variables, predicted performance, and measures of self efficacy; however, state and trait anxiety were not significantly related to pace of race. Results suggest that a task-specific measure of self-efficacy is the better predictor of performance in a race than a general measure of self efficacy. PMID- 8367252 TI - Using age-adjusted rates in ecological studies of suicide and homicide. PMID- 8367253 TI - An occluded contour becomes visible with reversal of disparity. AB - Suppose that there is a circle in front of a cross, the central part of which is occluded by the circle. One usually perceives these figures, as such, although the objective description of the stimulus pattern might be that there is a circle with four limbs attached to it. Here the occluded contours of the cross might be 'inferred.' Until now it has not been demonstrated clearly whether this 'inference' is based on higher cognitive processes or on perceptual processes. However, by manipulating binocular disparity so that the four limbs are seen in front of the circle, the occluded contours become visible, the color of the limbs spreads into the inside of the contours, and the color spreading surface appears transparent, suggesting that the 'inference' is on a perceptual basis. Interestingly, cornered subjective contours of the cross are observed. PMID- 8367255 TI - Topographical patterns of ERP elicited by different visual information-processing tasks. AB - Topographical patterns of event-related potentials were compared on a visual display terminal for a data-input task and a number-comparison task. Maximum negative peaks were found in the frontal and central regions for the former but at midline locations for the latter. Latencies were shorter in the occipital regions than in the frontal regions for the former and the opposite pattern was found for the latter. An analysis of variance indicated that hemispheric location significantly affected the amplitude of peaks. On the other hand, latencies were affected by the task, frontal and occipital regions, and their interaction. These results suggest that a pattern of the topographic display of event-related potentials can be used as an objective means for classifying visual tasks. PMID- 8367254 TI - Visuomotor control of the relative movement of random-dot patterns. AB - A series of experiments were made on human performance in controlling optical relative movement. The aim was to test the influence of different kinds of relative movement on visually controlled steering tasks. Within adjacent displays on a computer screen random dot patterns moved in a fixed direction at continually changing speeds (Exp. 1) or at constant speed and in continually changing directions (Exp. 2). The subject was required to compensate for the unpredictable modulations of the pattern movement by means of an isometric joystick. The task was to adjust relative movements involving pure translation, symmetric convergence, divergence, or shear. Analysis indicated that the task performance was not dependent on the special kind of relative movement. However, performance was significantly higher in tasks where directionally disturbed relative movement had to be controlled compared to those situations in which relative movement varied with respect to speed. PMID- 8367256 TI - Adults' free-form identification of emotions from children's descriptions of their antecedents: a quantitative analysis. AB - 50 adult subjects identified resultant emotions for 28 children's statements of antecedents to emotion in an open-ended task. Responses were scored along the dimensions of evaluation and activation by the Dictionary of Affect in Language, and a priori expectations with respect to evaluation (happy, proud, comfortable > sad, afraid, guilty, angry) and activation (sad, comfortable < angry, happy, proud, afraid, guilty) were confirmed. The importance of a dimensional approach to the study of emotion is highlighted in the discussion. PMID- 8367257 TI - Self-perceived somatotypes and clothing-related behavior of older men and women. AB - 507 older men and women (65 yr. or over) participated in an investigation of relationship between clothing-related behavior of older men and women and self perceived somatotypes. Analysis indicated that body-type was significantly related to significance of apparel, self-esteem, and chronological age. No sex differences were found in perception of body-types. Several implications are discussed and suggestions for further research are made. PMID- 8367258 TI - On the possibility of intermittence during fixations: a conceptual assessment. AB - A prevalent tacit assumption of the continuity of visual representation during fixations is challenged and shown to be logically tenuous. Relying upon three lines of suggestive evidence, it is then argued that representation must be in the form of static snapshots which alternate with very short dark periods wherein the image is omitted from vision. In view of the difficulties of a direct experimental verification of such a high-frequency intermittence, a conceptual approach to the question is defended. PMID- 8367259 TI - Rates of mental illness and suicide by state. PMID- 8367260 TI - Attention state in electrodermal activity during auditory stimulation of children with attention-deficit hyperactivity disorder. AB - Electrodermal activity during passive and active listening tasks of 18 children with Attention-Deficit Hyperactivity Disorder (ADHD) and 49 healthy school children was studied. The procedure included baseline recording, a passive listening task, instructions, and both simple and discriminative active-listening tasks. ADHD subjects tended to exhibit lower arousal as indicated by the decrease in amplitude of the skin conductance response. Present findings confirm classical observation that ADHD children have shorter attention spans. PMID- 8367261 TI - The horizontal-vertical illusion: transfer of illusion decrement. AB - Subjects first adjusted 20 vertical lines to be equal in length to the horizontal line in small or large inverted-T figures and were then given 10 additional trials on the other size figure. Vertical lines were made significantly shorter than the horizontal line but accuracy gradually improved and performance was not disrupted by the switch in figure size. By Trial 30, adjusted vertical lines did not differ from the length of the horizontal line. Other subjects were first tested on the small inverted-T figure and then asked to produce 1-in. lines in the vertical plane and in the horizontal plane. These subjects also improved on the adjustment task but, on the production task, were no more accurate than control subjects who were not given practice on the adjustment task. Thus, the magnitude of the Horizontal-Vertical Illusion decreases with practice alone and this practice effect readily transfers to figures of other sizes but not to an alternate form of the illusion. The potential factors responsible for the improvement and transfer are discussed. PMID- 8367262 TI - Repeated presentation of stimuli and production of original response by English speaking Indian high school students. AB - Sounds and Images, a measure of originality, was administered to 131 English speaking high school students of Orissa, India in 1987. The test has two forms, viz., IA and IB. Each form has four sounds which were presented three times. To each the students wrote their verbal images which were scored for originality and analyzed for effects of multiple presentation and differential sounds. The main effects of sounds (IA, IB), of presentation (IA), and the interaction of presentation by sound (IB) were nonsignificant, but presentation (IB) and the interaction of presentation by sound were significant. PMID- 8367263 TI - The stability of national suicide rates over time. PMID- 8367264 TI - Familial heart valve disorder is not related to autonomy, social interaction style, or family dynamics. PMID- 8367266 TI - When children talk about the causes of their emotions, how well do adults and other children understand which emotion they are talking about? AB - 100 subjects from Grade 2, Grade 5, and university levels decoded statements describing the antecedents of seven emotions produced by Kindergarten and Grade 8 students. The experiment was designed to determine whether adults and different children could correctly identify the emotions whose causes were being described by the children. Accuracy in decoding increased with age of decoder, but subjects from Grade 2 were better at decoding statements made by Kindergarten children while adults were better at decoding statements produced by Grade 8 subjects. Even for statements generated by Kindergarten children, however, adults were better decoders than subjects from Grades 2 or 5. The emotions of happiness and comfort were decoded most accurately, those of anger and guilt least accurately. Several other significant effects are reported, involving the age of origin, the age of respondent, and sex of origin and emotion. A cognitive developmental theory such as Piaget's is selected as best explaining the results reported above. PMID- 8367265 TI - Blink activity and task difficulty. AB - This study investigated the relationship between task difficulty and blink activity, which includes blink rate, blink amplitude, and blink duration. Two kinds of tasks established two levels of difficulty. In Exp. 1, a mental arithmetic task was used to examine the relationship. Analysis showed that blink rate for a difficult task was significantly higher than that for an easier one. In Exp. 2, a letter-search task (hiragana Japanese alphabet) was used while the other conditions were the same as those in Exp. 1; however, the results of this experiment were not influenced by the difficulty of the task. As results indicate that blink rate is related to not only difficulty but also the nature of the task, the nature of the task is probably dependent on a mechanism in information processing. The results for blink amplitude and blink duration showed no systematic change during either experiment. PMID- 8367267 TI - Proprioceptive responses under rising and falling BACs: a test of the Mellanby effect. AB - This study examined proprioceptive responses under equivalent rising and falling blood alcohol concentrations (BAC), using a repeated-measures design. Seven volunteer subjects, 21 to 35 years of age, participated in the study. After alcohol consumption, BAC readings were obtained every 5 minutes, and the proprioceptive responses were measured at the following BAC levels (in %): 0 (baseline), rising 0.05, 0.075, 0.1, falling 0.075, and 0.05. The analysis focused on the comparisons of these measures at the equivalent rising and falling 0.05% and at the 0.075% BACs. Results showed that the proprioceptive response was less accurate during the rising than the falling BACs. PMID- 8367269 TI - Community nursing centers: a viable alternative. PMID- 8367268 TI - Foot-tapping speed in children ages 4 to 6 years. AB - This investigation examined the performance and measurement characteristics of foot-tapping speed in 155 4- to 6-year-olds. Analysis suggested that, while the task does not differentiate between preferred and nonpreferred limbs, performance does appear to be age-related, that is, subjects tapped significantly faster with increasing age. Considering type of task and population, reliability was judged as moderate. PMID- 8367270 TI - Evaluation in nursing continuing education. PMID- 8367271 TI - The recovering nurse returning to work. PMID- 8367272 TI - New Jersey State Nurses' Association history: what is past is prologue. The ninth decade--1983-1992. PMID- 8367273 TI - Nursing as caring: a model for transforming practice. PMID- 8367274 TI - State-approved schools of nursing L.P.N./L.V.N. PMID- 8367275 TI - RNA polymerase I catalysed transcription of insert viral cDNA. AB - RNA polymerase I has been used for transcription of influenza hemagglutinin (HA) cDNA precisely linked in the anti-sense configuration to both mouse rDNA promoter and terminator segments. In transcription reactions based on Ehrlich ascites cell nuclear extracts, specific uniform RNA products are synthesized in high rates that are comparable to original rDNA template transcriptions. Primer extension reactions show the 5' ends of these RNA transcripts to be located exactly at position +1, corresponding to the 5' end of negative strand HA viral RNA. RNA 3' ends in a first series of constructs were found extended beyond the accepted location of pre-rRNA 3' ends, in using both hybrid cDNA and original rDNA templates. But upon deletion of six basepairs from the rDNA termination region RNA polymerase I transcription has been adapted to yield correctly terminated influenza viral RNA in vitro. This result has been confirmed in an in vivo experiment via synthesis of an anti-sense viral RNA molecule containing the chloramphenicol acetyltransferase (CAT) gene, which in turn is recognized at its terminal sequence by viral RNA dependent RNA polymerase for plus strand mRNA synthesis and expression of CAT activity. PMID- 8367276 TI - Domains of p85cdc10 required for function of the fission yeast DSC-1 factor. AB - p85cdc10 is a component of the S.pombe DSC-1 complex, which is thought to mediate periodic transcription of genes in late G1. In order to understand the role of p85cdc10 in the function of this complex, we have analysed which domains of p85cdc10 are required for biological activity and the formation of a stable DSC-1 complex in vitro, both in cdc10 temperature sensitive and null backgrounds. No DSC-1 activity is found in the absence of p85cdc10 and the activity of the complex is reduced or absent in all cdc10ts mutants tested. Full biological activity and rescue of a cdc10::ura4+ null allele requires the N-terminal domain, the cdc10/SWI6 repeats and the helical C-terminal region. In the absence of p85cdc10, both the C-terminal and cdc10/SWI6 repeat domains are required for DSC 1 activity in vitro. In a cdc10ts background, rescue of DSC-1 activity and complementation of mutants, requires only expression of the C-terminal domain, though the presence of the cdc10/SWI6 motifs enhances its activity. The N terminal domain, alone, or in combination with the cdc10/SWI6 motifs, does not have biological activity, and does not restore DSC-1 activity. We conclude that both the C-terminal domain of p85cdc10 is critical for formation of the DSC-1 complex and that the cdc10/SWI6 motifs also play a role, perhaps by stabilizing the complex. Our data also suggest that the S.pombe DSC-1 complex contains more than one molecule of p85cdc10. PMID- 8367277 TI - Mutagenically separated PCR (MS-PCR): a highly specific one step procedure for easy mutation detection. AB - With increasing knowledge about the causal role of genetic defects in clinical diseases the necessity is apparent to have procedures for rapid diagnosis of point mutations. We developed a PCR-based technique, whereby both normal and mutant alleles can be amplified in the same reaction tube, using different length allele-specific primers. Furthermore the allele-specific primers introduce additional deliberate differences into the allelic PCR-products that drastically reduce crossreactions in subsequent cycles. This mutagenesis separates the amplification reactions of the alleles performed in the same tube. Subsequent identification of the PCR-products is done by gel electrophoresis and shows at least one of the two allelic products. Therefore, in addition to simple handling, MS-PCR provides a within-assay quality control for the exclusion of false negative results. The feasibility of this technique has been tested using six different mutations. The high sensitivity of MS-PCR also allows screening for mutation carriers in pooled DNA samples. PMID- 8367279 TI - 'Cold SSCP': a simple, rapid and non-radioactive method for optimized single strand conformation polymorphism analyses. AB - A rapid (< 2.5 hrs) method for single-strand conformation polymorphism (SSCP) analysis of PCR products that allows the use of ethidium bromide staining is described. PCR products ranging in size from 117 to 256 bp were evaluated for point mutations and polymorphisms by 'cold SSCP' in commercially available pre cast polyacrylamide mini-gels. Several electrophoretic parameters (running temperature, buffers, denaturants, DNA concentration, and gel polyacrylamide concentration) were found to influence the degree of strand separation and appeared to be PCR fragment specific. Use of the 'cold' SSCP technique and the mini-gel format allowed us to readily optimize the electrophoretic conditions for each PCR fragment. This greatly increased our ability to detect polymorphisms compared to conventional, radioisotope-labeled 'hot' SSCP, typically run under two standard temperature conditions. Excellent results have been obtained in resolving mutant PCR fragments from human p53 exons 5 through 8, human HLA-DQA, human K-ras exons 1 and 2, and rat K-ras exon 3. Polymorphisms could be detected when mutant DNA comprised as little as 3% of the total gene copies in a PCR mixture. Compared to standard 'hot' SSCP, this novel non-isotopic method has additional advantages of dramatically increased speed, precise temperature control, reproducibility, and easily and inexpensively obtainable reagents and equipment. This new method also lacks the safety and hazardous waste management concerns associated with radioactive methods. PMID- 8367278 TI - Transcription of human 5S rRNA genes is influenced by an upstream DNA sequence. AB - Six human 5S rRNA genes and gene variants and one pseudogene have been sequenced. The six genes/variants were transcribed in a HeLa cell extract with about equal efficiency. Three genes contain the Sp1 binding sequence GGGCGG in position -43 to -38 and three genes contain the Sp1 like sequence GGGCCG in this position. The six genes contain furthermore one Sp1 binding site in a position about -245 and one ATF recognition site in a position about -202. A 12 bp sequence (GGCTCTTGGGGC) found in position -32 to -21 strongly influenced the transcriptional efficiency in vitro. This 12-mer, designated the D box, has also been found upstream a 5S rRNA gene from hamster and mouse. Removal of the Sp1 binding sites had no effect on the transcription in vitro whereas the transcriptional efficiency decreased to 10% if the D box was removed from the human 5S rRNA gene. PMID- 8367281 TI - Differential expression of principal sigma factor homologues of Streptomyces aureofaciens correlates with the developmental stage. AB - In previous experiments, Streptomyces aureofaciens has been shown to contain four genes hrdA, hrdB, hrdD, and hrdE, encoding polypeptides very similar to principal sigma factors of RNA polymerase. Two apparent tandem promoters were identified for each of the hrdA, hrdB and hrdD genes by S1 nuclease mapping using RNA prepared of S. aureofaciens in various developmental stages. Under all the conditions studied, tandem promoters of each gene differed significantly in their respective strengths. Transcription from the hrd promoters depended on developmental stage. While hrdB is transcribed from both promoters in all developmental stages, both tandem promoters of the hrdD gene are active only in vegetative stage and transcription of the hrdA tandem promoters temporally correlates with the aerial mycelium formation. In addition to a promoter, hrdB P2, which lies upstream of the open reading frame, the hrdB gene, proposed to encode functional principal factor, appeared to contain at least one internal promoter, hrdB-P1. Activity of all promoters was consistent with S1 mapping experiments after insertion of promoter-bearing DNA fragments to promoter-probe vectors pIJ486 and pARC1. The results implicate temporally different expression of the hrd genes during the differentiation of S. aureofaciens. PMID- 8367280 TI - The gene encoding DNA polymerase alpha from Plasmodium falciparum. AB - The gene encoding DNA polymerase alpha from the human malaria parasite Plasmodium falciparum has been sequenced and characterised. The deduced amino acid sequence possesses the seven sequence motifs which characterise eukaryotic replicative DNA polymerases (I-VII) and four of five motifs (A-E) identified in alpha DNA polymerases. The predicted protein also contains sequences which are reminiscent of Plasmodium proteins but absent from other DNA polymerases. These include four blocks of additional amino acids interspersed with the conserved motifs of the DNA polymerases, four asparagine rich sequences and a novel carboxy-terminal extension. Repetitive sequences similar to those found in other malarial proteins are also present. cDNA-directed PCR was used to establish the presence of these features in the approximately 7kb mRNA. The coding sequence contains a single intron. The gene for DNAPol alpha is located on chromosome 4 and is transcribed in both asexual and sexual erythrocytic stages of the parasite. PMID- 8367282 TI - Homologous pairing between single-stranded DNA immobilized on a nitrocellulose membrane and duplex DNA is specific for RecA activity in bacterial crude extract. AB - Reaction between a circular single stranded and a linear double stranded DNA molecule (ssDNA and dsDNA) provides an efficient system to study recombination mediated by RecA protein. However, classical assays using reaction in solution require highly purified enzymes. This limits biochemical studies of mutant RecA proteins from Escherichia coli or of RecA proteins from other organisms. We describe here an assay that is specific for RecA activity even in bacterial crude extracts. In this assay, the ssDNA is bound to a nitrocellulose membrane, proteins are loaded on this membrane and it is then incubated with a labeled homologous dsDNA. Joint molecules are visualized by autoradiography. We have shown that, despite the reduced mobility of the DNA due to its binding to the membrane, RecA protein is able to promote formation of stable plectonemic joints, in a homology dependent manner. Fourteen other proteins involved in DNA metabolism were checked and did not produce a signal in our assay. Moreover, in Dot blot analysis as well as after native electrophoresis and electrotransfer on a ssDNA coated membrane, production of a signal was strictly dependent on the presence of active RecA protein in the bacterial crude extracts used. We named this assay Pairing On Membrane blot (POM blot). PMID- 8367283 TI - Sigma s-dependent promoters in Escherichia coli are located in DNA regions with intrinsic curvature. AB - Expression of a number of genes during stationary phase in Escherichia coli is controlled by the alternative sigma factor sigma s (KatF). Promoters recognized by sigma s do not present a well-defined consensus sequence in their -10 and -35 regions. By polyacrylamide gel electrophoresis of DNA fragments performed at different temperatures, and by computer prediction analyses, we have found that sigma s-regulated promoters are located in regions where DNA shows intrinsic curvatures. This feature does not appear in a stationary-phase-induced promoter which is not controlled by sigma s. We propose that DNA bending may help in recognition and/or binding of sigma s to stationary-phase-induced promoters. PMID- 8367284 TI - A quantitative assay to measure the relative DNA-binding affinity of pyrrolo[2,1 c] [1,4]benzodiazepine (PBD) antitumour antibiotics based on the inhibition of restriction endonuclease BamHI. AB - An assay has been developed (restriction endonuclease digestion assay--RED100) based on inhibition of the restriction endonuclease BamHI that is capable of quantitative evaluation of the relative DNA-binding affinity of pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) antitumour antibiotics. This method provides comparable results to those obtained from thermal denaturation and ethidium bromide displacement assays but is much more sensitive, discriminating between molecules of similar structure such as DC-81, iso-DC-81 and neothramycin. The results reveal a trend between relative DNA-binding affinity and in vitro cytotoxicity for the PBDs in two tumour cell lines studied. PMID- 8367285 TI - I-Sce III an intron-encoded DNA endonuclease from yeast mitochondria. Asymmetrical DNA binding properties and cleavage reaction. AB - We have previously discovered the new intron-encoded endonuclease I-Sce III by expressing, in E. coli, the ORF contained in the third intron of the yeast mitochondrial COX I gene. In this work, we analyzed the in vitro properties of partially purified I-Sce III and found that it is a very specific DNA endonuclease, tolerating relatively few base changes in its 20 base pair long target site. I-Sce III should be a useful molecular tool to analyze the structure of large genomes. Interestingly, I-Sce III is the first P1-P2 DNA endonuclease for which DNA binding properties could be analyzed by band-shift experiments. Clearly, the cleavage products corresponding to the upstream A3 exon and to the downstream A4 exon could compete with the substrate A3-A4 in forming a DNA protein complex. However, the A3 exon competes more efficiently than the downstream A4 product. The cleavage of the two DNA strands is also asymmetric the top strand (non-transcribed strand) is cleaved faster than the bottom strand, a property found under various experimental conditions. These findings suggest that this intron-encoded DNA endonuclease may have role in the RNA splicing process of the intron. PMID- 8367286 TI - Zinc fingers in sex determination: only one of the two C. elegans Tra-1 proteins binds DNA in vitro. AB - The tra-1 gene of Caenorhabditis elegans is a major developmental regulator that promotes female development. Two mRNAs are expressed from the tra-1 locus as a result of alternative mRNA processing. One mRNA encodes a protein with five zinc fingers and the other a protein with only the first two zinc fingers. We have derived a preferred in vitro DNA binding site for the five finger protein by selection from random oligonucleotides. The two finger protein does not bind to DNA in vitro. Moreover, removal of the first two fingers from the five finger protein does not eliminate binding and has little effect on its preferred binding site. We find that a protein sequence amino-terminal to the finger domain also appears to play a role in DNA binding. PMID- 8367287 TI - In vitro replication of bacteriophage PRD1 DNA. Characterization of the protein primed initiation site. AB - Bacteriophage PRD1 replicates its DNA by means of a protein-primed replication mechanism. Using single-stranded oligonucleotide templates carrying the sequence corresponding to the 25 first bases of the 3' end of PRD1 DNA, and Mg2+ as the activating metal ion of the phage DNA polymerase, we show that the fourth base from the 3' end of the template directs, by base complementarity, the dNMP to be linked to the phage terminal protein (TP) in the initiation reaction. This result suggests that phage PRD1 maintains its 3' end DNA sequences via a sliding-back mechanism. The single-stranded DNA templates could not be replicated by the PRD1 DNA polymerase, much in contrast to the natural TP-DNA. Nevertheless, the analysis of the transition products obtained with TP-DNA and origin-containing oligonucleotides suggests that sliding-back occurs stepwise, the fourth base being the directing position during the entire process. PMID- 8367288 TI - Analysis of the rat hepatocyte nuclear factor (HNF) 1 gene promoter: synergistic activation by HNF4 and HNF1 proteins. AB - Hepatocyte nuclear factor (HNF) 1 is a key transcription factor involved in the expression of many liver-specific genes. We have isolated and characterized the promoter region of the rat HNF1 gene. Transfection experiments revealed that a short region between -118 and -8 is crucial for cell type-specific expression of the HNF1 gene in the hepatoma cell line, HepG2 cells. This region contains two positive cis-elements: site A, to which the transcription factor HNF4 protein can bind, and site B, to which the HNF1 protein can bind. Mutational analyses of these sites and cotransfection assays suggested that the HNF4 protein and HNF1 protein can transactivate the HNF1 gene. PMID- 8367289 TI - Tritium labeling of antisense oligonucleotides by exchange with tritiated water. AB - We describe a simple, efficient, procedure for labeling oligonucleotides to high specific activity (< 1 x 10(8) cpm/mumol) by hydrogen exchange with tritiated water at the C8 positions of purines in the presence of beta-mercaptoethanol, an effective radical scavenger. Approximately 90% of the starting material is recovered as intact, labeled oligonucleotide. The radiolabeled compounds are stable in biological systems; greater than 90% of the specific activity is retained after 72 hr incubation at 37 degrees C in serum-containing media. Data obtained from in vitro cellular uptake experiments using oligonucleotides labeled by this method are similar to those obtained using 35S or 14C-labeled compounds. Because this protocol is solely dependent upon the existence of purine residues, it should be useful for radiolabeling modified as well as unmodified phosphodiester oligonucleotides. PMID- 8367290 TI - Three-step PCR mutagenesis for 'linker scanning'. AB - 'Linker scanning' has been used as an efficient method for systematically surveying a segment of DNA for functional elements by mutagenesis. A three-step PCR method was developed to simplify this process. In this method, a set of 'mutation primers' was made with 6 to 8 base substitutions in the center of the primers. In the first PCR reaction, these 'mutation primers' are paired with an 3' primer from the opposite end of the analyzed sequences to form a 'ladder' of fragments containing the base pair substitutions. These are used as templates in the second PCR with the 3' primer as the only primer to generate single stranded sequences, which are used as primers in the third PCR paired with an 5' primer to complete the mutagenesis. We have tested the method in a mutation screen of the steroid sulfatase promoter. Its application to general site specific mutagenesis is discussed. PMID- 8367291 TI - Subunits of the Schizosaccharomyces pombe RNA polymerase II: enzyme purification and structure of the subunit 3 gene. AB - To improve our understanding of the structure and function of eukaryotic RNA polymerase II, we purified the enzyme from the fission yeast Schizosaccharomyces pombe. The highly purified RNA polymerase II contained more than eleven polypeptides. The sizes of the largest the second-, and the third-largest polypeptides as measured by SDS-polyacrylamide gel electrophoresis were about 210, 150, and 40 kilodaltons (kDa), respectively, and are similar to those of RPB1, 2, and 3 subunits of Saccharomyces cerevisiae RNA polymerase II. Using the degenerated primers designed after amino acid micro-sequencing of the 40 kDa third-largest polypeptide (subunit 3), we cloned the subunit 3 gene (rpb3) and determined its DNA sequence. Taken together with the sequence of parts of PCR amplified cDNA, the predicted coding sequence of rpb3, interrupted by two introns, was found to encode a polypeptide of 297 amino acid residues in length with a molecular weight of 34 kDa. The S. pombe subunit 3 contains four structural domains conserved for the alpha-subunit family of RNA polymerase from both eukaryotes and prokaryotes. A putative leucine zipper motif was found to exist in the C-terminal proximal conserved region (domain D). Possible functions of the conserved domains are discussed. PMID- 8367293 TI - Allelic discrimination by nick-translation PCR with fluorogenic probes. AB - Nick-translation PCR was performed with fluorogenic probes. Two probes were used: one complementary to a sequence containing the F508 codon of the normal human cystic fibrosis (CF) gene (wt DNA) and one complementary to a sequence containing the delta F508 three base pair deletion (mut DNA). Each probe contained a unique and spectrally resolvable fluorescent indicator dye at the 5' end and a common quencher dye attached to the seventh nucleotide from the 5' end. The F508/delta F508 site was located between the indicator and quencher. The probes were added at the start of a PCR containing mut DNA, wt DNA or heterozygous DNA and were degraded during thermal cycling. Although both probes were degraded, each probe generated fluorescence from its indicator dye only when the sequence between the indicator and quencher dyes was perfectly complementary to target. The identify of the target DNA could be determined from the post-PCR fluorescence emission spectrum. PMID- 8367292 TI - Site-specific mutagenesis induced by single O6-alkylguanines (O6-n-propyl, O6-n butyl, O6-n-octyl) in vivo. AB - The mutagenic activity of a series of longer chain O6-n-alkylguanine residues (O6 n-propyl, O6-n-butyl, O6-n-octyl) has been analyzed using a plasmid molecule (pUC 9) in which single O6-alkylguanines were positioned in the unique Pstl recognition site by shot gun ligation (Nucleic Acids Res. 13, 3305-3316 (1985)) of overlapping synthetic oligonucleotides. After transfection of these vectors into E. coli cells having normal DNA repair systems, progeny plasmids were produced, of which 2.6%, 2.8% and 4.3% were mutated in their Pstl site when containing O6-n-propylguanine, O6-n-butylguanine, O6-n-octylguanine, respectively. DNA sequence analysis of mutant plasmid genomes revealed that O6-n propylguanine and O6-n-butylguanine induced exclusively G-->A transitions located specifically at the preselected site. O6-n-octylguanine induced apart from G-->A transitions (70%) also targeted G-->T transversions (30%). These results indicate that the mutation frequency of longer chain O6-alkylguanines can be substantial in cells with normal repair systems and that the mutation pattern depends on the nature of the alkyl group. PMID- 8367295 TI - The DAL82 protein of Saccharomyces cerevisiae binds to the DAL upstream induction sequence (UIS). AB - Expression of the DAL2, DAL4, DAL7, DUR1,2, and DUR3 genes in S. cerevisiae is induced by allophanate, the last intermediate in the allantoin catabolic pathway. Analysis of the DAL7 promoter identified a dodecanucleotide, the DAL7 UIS, which was required for inducer-responsiveness. Operation of the DAL7 UIS required functional DAL81 and DAL82 gene products. Since the DAL81 product was not an allantoin pathway-specific regulatory factor, the DAL82 product was considered as the more likely candidate to be the DAL UIS binding protein. Using an E. coli expression system, we showed that DAL82 protein specifically bound to wild type but not mutant DAL UIS sequences. DNA fragments containing DAL UIS elements derived from various DAL gene promoters bound DAL82 protein with different affinities which correlate with the degree of inducer-responsiveness the genes displayed. PMID- 8367296 TI - Tetramethylammonium does not universally neutralize sequence dependent DNA stability. AB - Effects of different concentrations of Tetramethylammonium on the thermostability of six DNA dumbbells with similar well defined sequences have been investigated. Each molecule has a 16 base pair duplex stem linked on both ends by T4 single strand loops. Only the sequence of the four central base pairs distinguishes one molecule from the next. The distinguishing central sequences are, [A-T-A-T], [T-A T-A], [A-A-A-A], [C-G-C-G], [G-C-G-C] and [G-G-G-G] situated between the sequences: 5'-G-T-A-T-C-C-[]-G-G-A-T-A-C-3' which are the same in all molecules. Optical melting curves collected on these molecules as a function of TMA concentration over the range from 0.09 M to 4.5 M revealed there is no single concentration of TMA where all these molecules exhibit the same melting temperature. PMID- 8367294 TI - Transcriptional repressor ZF5 identifies a new conserved domain in zinc finger proteins. AB - We have cloned a cDNA encoding a new murine C2H2 zinc finger protein, ZF5. The 51.3 kD protein contains five GL1-Kruppel type zinc fingers at the C-terminus. At its N-terminus, ZF5 has a 41 amino acid region which was found to be homologous to the N-termini of several other zinc finger proteins. This region defines a new motif within zinc finger proteins which we have named the Zinc finger N-terminal (ZiN) domain. ZF5 binds to two sites in the c-myc promoter and to the -50 bp site of the herpes simplex thymidine kinase promoter. ZF5 is a transcriptional repressor and its repression domain is located N-terminal to the zinc finger domains. A single 4 kb ZF5 mRNA is expressed widely. PMID- 8367297 TI - Molecular characterization of the yeast meiotic regulatory gene RIM1. AB - In the yeast Saccharomyces cerevisiae, genetic studies suggest that the RIM1 gene encodes a positive regulator of meiosis. rim1 mutations cause reduced expression of IME1, which is required for expression of many meiotic genes, and thus lead to a partial defect in meiosis and spore formation. We report the sequence of RIM1 and functional analysis of its coding region. The RIM1 gene product (RIM1) contains three regions similar to C2H2 zinc fingers. Serine substitutions for cysteine in each of the putative zinc fingers abolish RIM1 function. The carboxyl terminus of RIM1 is enriched in acidic amino acids and is required for full RIM1 activity. RIM1 also contains two putative cAMP-dependent protein kinase (cAPK) phosphorylation sites. At one site, substitution of alanine for serine does not affect RIM1 activity; at the other site, this substitution impairs activity. This analysis of RIM1 suggests that the protein may function as a transcriptional activator. We have used the cloned RIM1 gene to create a complete rim1 deletion. This null allele, like previously isolated rim1 mutations, causes a partial meiotic defect. In addition to RIM1, maximum IME1 expression requires the MCK1 and IME4 gene products. Defects associated with rim1, mck1, and ime4 mutations in expression of a meiotic reporter gene (ime2-lacZ) and in sporulation are additive. These findings suggest that RIM1 acts independently of MCK1 and IME4 to stimulate IME1 expression. PMID- 8367298 TI - p21X mRNA is expressed as a singly spliced pX transcript from defective provirus genomes having a partial deletion of the pol-env region in human T-cell leukemia virus type 1-infected cells. AB - In addition to the three typical transcripts such as genomic/gag-pol mRNA, env mRNA and tax/rex mRNA, we previously found the singly spliced pX mRNA, termed p21X mRNA, responsible for producing the p21X protein in human T-cell leukemia virus type 1 (HTLV-1)-infected cells. Our finding of the p21X mRNA being constitutively expressed in the fresh peripheral blood mononuclear cells (PBMCs) from patients with ATL has suggested that the expression mechanism is quite different from that of the others. In this paper, the expression mechanism of p21X mRNA was investigated by analyzing the organization of the proviral genomes present in the representative HTLV-1-infected cell lines which are positive or negative for the expression of p21X mRNA. Southern and PCR analyses show that most of the analyzed cell lines contain both one complete and one defective genome each. However, one cell line without the p21X mRNA expression, C91/PL, contains only the complete genome, suggesting that the complete HTLV-1 has no ability to express p21X mRNA in spite of having the ability to produce the infectious virus. The defective genomes of the p21X mRNA positive cell lines, MT 2 and H582, have a large deletion of the entire pol and parts of the gag and env regions including the common domain of the second exon of the doubly spliced tax/rex mRNA, while another defective genome of the p21X mRNA negative cell line, MT-1, has a deletion within the gag-pol gene. We show that these defective genomes have the ability to express their distinct, defective genomic mRNA, suggesting they are active. The defective genomic mRNAs in MT-2 and H582 cells retain the first splice donor and the second splice acceptor sites, suggesting the possibility of synthesizing p21X mRNA by splicing singly with these sites. These findings assume that defective HTLV-1 genomes deleting the second exon region acquire the ability to express p21X mRNA but no ability to express tax/rex mRNA. Such a deletion may explain the difference between the expression mechanisms in the p21X mRNA transcript and those in the other viral transcripts. PMID- 8367299 TI - Problems related to the interpretation of autoradiographic data on gene expression using common constitutive transcripts as controls. AB - The 28S rRNA, a ribosomal RNA, and the ACTB and GAPD mRNAs, coding respectively for beta-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are frequently presented as controls of modulated gene expression. These transcripts were quantified by replicate slot-blot autoradiography and image analysis in mammary epithelial cells and fibroblasts from breast tissues. Each cell-type group comprised strains with different pathological backgrounds, growth rates, antigenic phenotypes and culture histories. The effects of a differentiating agent (cholera toxin) and/or a tumor promoter (12-O-tetradecanoyl-phorbol-13 acetate) were also examined. Despite the impression that visual examination of autoradiographs might create, image analysis suggests that 28S rRNA, ACTB and GAPD are substantially and independently influenced by the above biological factors and by the drugs. Therefore, these transcripts represent specifically regulated cellular activities and may not be taken as alternative indicators of the overall transcription rate or of the amount of material being examined. Instead, such nonspecific variation may be accurately measured and removed from quantitative data using a principal component function. A methodology that allows comparison of expression (or amplification) patterns between genes, between experiments or, even, between laboratories is presented with an example of quantification of transcripts related to cell-growth, differentiation, signaling and cancer. PMID- 8367300 TI - Fission yeast with DNA polymerase delta temperature-sensitive alleles exhibits cell division cycle phenotype. AB - DNA polymerases alpha and delta are essential enzymes believed to play critical roles in initiation and replication of chromosome DNA. In this study, we show that the genes for Schizosaccharomyces pombe (S.pombe) DNA polymerase alpha and delta (pol alpha+ and pol delta+) are essential for cell viability. Disruption of either the pol alpha+ or pol delta+ gene results in distinct terminal phenotypes. The S.pombe pol delta+ gene is able to complement the thermosensitive cdc2-2 allele of Saccharomyces cerevisiae (S.cerevisiae) at the restrictive temperature. By random mutagenesis in vitro, we generated three pol delta conditional lethal alleles. We replaced the wild type chromosomal copy of pol delta+ gene with the mutagenized sequence and characterized the thermosensitive alleles in vivo. All three thermosensitive mutants exhibit a typical cell division cycle (cdc) terminal phenotype similar to that of the disrupted pol delta+ gene. Flow cytometric analysis showed that at the nonpermissive temperature all three mutants were arrested in S phase of the cell cycle. The three S.pombe conditional pol delta alleles were recovered and sequenced. The mutations causing the thermosensitive phenotype are missense mutations. The altered amino acid residues are uniquely conserved among the known polymerase delta sequences. PMID- 8367301 TI - A quality control algorithm for DNA sequencing projects. AB - Heterologous DNA sequences from rearrangements with the genomes of host cells, genomic fragments from hybrid cells, or impure tissue sources can threaten the purity of libraries that are derived from RNA or DNA. Hybridization methods can only detect contaminants from known or suspected heterologous sources, and whole library screening is technically very difficult. Detection of contaminating heterologous clones by sequence alignment is only possible when related sequences are present in a known database. We have developed a statistical test to identify heterologous sequences that is based on the differences in hexamer composition of DNA from different organisms. This test does not require that sequences similar to potential heterologous contaminants are present in the database, and can in principle detect contamination by previously unknown organisms. We have applied this test to the major public expressed sequence tag (EST) data sets to evaluate its utility as a quality control measure and a peer evaluation tool. There is detectable heterogeneity in most human and C.elegans EST data sets but it is not apparently associated with cross-species contamination. However, there is direct evidence for both yeast and bacterial sequence contamination in some public database sequences annotated as human. Results obtained with the hexamer test have been confirmed with similarity searches using sequences from the relevant data sets. PMID- 8367302 TI - RAD50 protein of S.cerevisiae exhibits ATP-dependent DNA binding. AB - RAD50 function of Saccharomyces cerevisiae is required during vegetative growth for recombinational repair of DNA double strand breaks, and during meiosis for initiation of meiotic recombination and formation of synaptonemal complex. RAD50 encodes a 153 kDa polypeptide which includes an amino-terminal ATP binding domain essential for function and two long heptad repeat regions. We show below that RAD50 protein purified from yeast exhibits ATP-dependent binding to double stranded DNA. Physical properties of the purified protein are also described. Models for RAD50 function in vivo are discussed. PMID- 8367303 TI - Evaluation of the contingent replication assay (CRA) and its application to the study of the general transcription initiation factor, TFIIF. AB - The Contingent replication assay (CRA) is a rapid assay for the screening and isolation of cDNAs by protein-protein or protein-DNA interactions in mammalian cells. The method has been shown to enrich a plasmid containing a cDNA encoding the bacterial replication-related protein, R6K, from a mixture of two plasmids. In this report we present data illustrating the sensitivity and selectivity of the method. Using the small subunit of TFIIF (Rap30) as a target, we demonstrate the enrichment of a clone encoding the large subunit, Rap74, from a cDNA library. Additional cDNA clones including human Rap30 and an anonymous cDNA clone homologous to members of the human cdc2 kinase family were enriched and isolated by a modified screening approach. The structure of these additional clones suggest that the CRA enriches for products that interact not only directly with the target protein but also through bridging by endogenous proteins. PMID- 8367304 TI - Comparative DNA sequence features in two long Escherichia coli contigs. AB - The recent sequencing of two relatively long (approximately 100 kb) contigs of E.coli presents unique opportunities for investigating heterogeneity and genomic organization of the E.coli chromosome. We have evaluated a number of common and contrasting sequence features in the two new contigs with comparisons to all available E.coli sequences (> 1.6 Mb). Our analyses include assessments of: (i) counts and distributions of restriction sites, special oligonucleotides (e.g., Chi sites, Dam and Dcm methylase targets), and other marker arrays; (ii) significant distant and close direct and inverted repeat sequences; (iii) sequence similarities between the long contigs and other E.coli sequences; (iv) characterization and identification of rare and frequent oligonucleotides; (v) compositional biases in short oligonucleotides; and (vi) position-dependent fluctuations in sequence composition. The two contigs reveal a number of distinctive features, including: a cluster of five repeat/dyad elements with very regular spacings resembling a transcription attenuator in one of the contigs; REP elements, ERICs, and other long repeats; distinction of the Chi sequence as the most frequent oligonucleotide; regions of clustering, overdispersion, and regularity of certain restriction sites and short palindromes; and comparative domains of inhomogeneities in the two long contigs. These and other features are discussed in relation to the organization of the E.coli chromosome. PMID- 8367305 TI - Sequence of the Rhizobium leguminosarum biovar phaseoli syrM gene. PMID- 8367307 TI - Nucleotide sequence of the small subunit rRNA of Ameson michaelis. PMID- 8367306 TI - Isolation of a murine gene encoding a nucleic acid-binding protein with homology to hnRNP K. PMID- 8367308 TI - The complete nucleotide sequence of a pathogenic swine vesicular disease virus isolated in Japan (J1'73) and phylogenetic analysis. PMID- 8367309 TI - Drosophila ribosomal protein S19 cDNA sequence. PMID- 8367310 TI - The nuclear 18S ribosomal RNA gene of the red alga Hildenbrandia rubra contains a group I intron. PMID- 8367312 TI - The primary sequence of the Schizosaccharomyces pombe protein homologous to S.cerevisiae ribosomal protein L2. PMID- 8367311 TI - Cloning and expression of the NspV restriction-modification genes of Nostoc sp. strain PCC7524. PMID- 8367313 TI - Nucleotide sequence of a Trypanosoma cruzi cDNA encoding a protein homologous to mammalian EF1 gamma. PMID- 8367314 TI - Electrophoretic karyotype of budding yeasts with intact cell wall. PMID- 8367315 TI - Analysis of oligonucleotide structure using hyperchromism measurements at long wavelengths. PMID- 8367316 TI - Excess PCR primers may dramatically affect SSCP efficiency. PMID- 8367317 TI - Construction of random small-insert genomic libraries highly enriched for simple sequence repeats. PMID- 8367318 TI - Sequencing of cDNA using anchored oligo dT primers. PMID- 8367319 TI - A novel method employing UNG to avoid carry-over contamination in RNA-PCR. PMID- 8367320 TI - Airway emergencies in the post anesthesia care unit. AB - Airway emergencies are frequently seen in the PACU. Six of the more common airway emergencies have been discussed. The upper-airway emergencies discussed included soft tissue obstruction, laryngeal edema, and laryngospasm. The lower-airway emergencies discussed included bronchospasm, noncardiogenic pulmonary edema, and aspiration. The PACU nurse must be ever vigilant. Knowing the definition, pathophysiology, signs and symptoms, patients at risk, and treatment modalities should prepare the PACU nurse for immediate response in the event of a crisis. Many times, the speed in which the emergency is identified and the treatment is begun determines the final outcome for the patient. PMID- 8367321 TI - Cardiovascular emergencies in the post anesthesia care unit. AB - Optimizing the cardiac function of the postanesthesia patient is dependent on identifying the possible causes of dysfunction. The causes of alterations in cardiac function are varied and complex. The PACU nurse must possess a knowledge of cardiac physiology, an intricate understanding of the cardiovascular effects of various anesthetic agents, and astute assessment skills. PMID- 8367323 TI - The pediatric patient in the post anesthesia care unit. AB - This article provides an overview of pediatric post anesthesia care. It highlights important aspects of care that are frequently encountered in practice or have the potential for being problematic. These include airway management, fluid maintenance, the treatment of seizures, thermoregulation, the management of malignant hyperthermia, the identification and treatment of emergence delirium, and the availability of appropriate emergency equipment and medications. PMID- 8367322 TI - The elderly patient in the post anesthesia care unit. AB - This article discusses the implications of providing care to the elderly patient in the post anesthesia care unit (PACU). Using a systems approach, physiologic changes along with pharmacologic and pathophysiologic alterations associated with aging are identified. Anesthetic options are presented; and postoperative priorities and nursing implications for the elderly patient are also included. PMID- 8367324 TI - Ambulatory surgical patient priorities. AB - With the increasing numbers of ambulatory surgical patients, anesthetic and post anesthetic care priorities have been identified with the goal of providing safe care and a timely discharge. This article focuses on patient selection, anesthetic options, pain management, nausea and vomiting, and discharge priorities. Collaboration between nursing, anesthesia, and surgical personnel is emphasized throughout. PMID- 8367325 TI - Local and regional anesthesia. Nursing implications. AB - Local and regional anesthesia offers many advantages and is relatively safe, resulting primarily in positive outcomes for the patient. The potential for complications and the need for patient education, however, dictate that the PACU nurse prepare the patient appropriately, remain vigilant, and initiate the necessary measures for monitoring and intervention when caring for such patients in both the preanesthesia and postanesthesia phases. Local and regional anesthetic agents and techniques have been discussed along with their implications for nursing care. Readers are also encouraged to consult the references and their own institutional policies for additional information. PMID- 8367326 TI - Assessing and improving quality in the post anesthesia care unit. AB - The Joint Commission on Accreditation of Healthcare Organization's 10 step methodology for quality assessment and improvement is a powerful tool for addressing and resolving complex interdisciplinary problems and issues. This article presents the basics of each of the 10 steps to illustrate a post anesthesia care unit (PACU) monitoring and evaluation process that is rigorous, objective, systematic, and relevant. In addition, two quality improvement tools, flow charts and cause-and-effect diagrams, are discussed. PMID- 8367327 TI - Prevention and control of tuberculosis in the 1990s. AB - Beginning in 1984, the long-term decline in tuberculosis (TB) cases stopped, and since 1985 the number of cases has actually increased by 18%, from 22,201 new cases in 1985 to 26,283 in 1991. The change in the morbidity trend appears to be primarily due to three factors: HIV coinfection, TB occurring in persons from countries where this disease is prevalent, and deterioration of the health care infrastructure with resultant outbreaks of TB. This article presents six interventions that address major areas where action is needed. These efforts will require coordinated action by health care providers, public health departments, and other public and private organizations. Protection of all workers and patients in health care settings is one important goal of these efforts. PMID- 8367328 TI - The influence of the Occupational Safety and Health Administration on infection control practice. AB - Beginning with the Occupational Safety and Health Administration's (OSHA) activities to enforce the Centers for Disease Control (CDC) and Prevention guidelines on Universal Precautions in 1987, this agency has had a direct and sustained impact on infection control programs. This article details how OSHA works, the OSHA inspection process, the bloodborne pathogens standard, current promulgation activities, other OSHA standards, OSHA reform, and the future of this agency. PMID- 8367329 TI - Methicillin-resistant Staphylococcus aureus. Past, present, and future. AB - The MRSA control program at UCDMC is one of many approaches used in hospitals today. With this less restrictive program, we have been able to maintain control of MRSA for approximately 5 years. By establishing a threshold for investigation at four new nosocomial cases per month, the ICD has been able to maintain a manageable endemic level of MRSA. Figure 2 shows the downward trend of new cases of MRSA per fiscal year. During 1991, however, we experienced clustering of cases in two areas of the hospital along with a major outbreak in our burn unit. This is reflected in the significant rise in the number of new cases for that year. Even with these outbreaks, however, we have been able to re-establish control. Figure 3 represents the number of new MRSA cases per month during fiscal year 1991. After the peak in April, we have again seen a downward trend, with an average of four new cases per month during the first quarter of fiscal year 1992. The success of this program is attributed to the cooperation and excellent communication among the hospital departments who are active participants in this control program. It is also owing to the establishment of a very active antibiotic control program that discourages inappropriate use of antimicrobial agents. This team effort is critical to the success of any infection control program. Infection control protocols are constantly changing, even if they are directed toward the same pathogen. Hospital epidemiology provides us with a very systematic approach to controlling the spread of disease. During the process, however, we are constantly collecting new information about the pathogen, allowing us to re-evaluate and, we hope, improve our approach to control. This is one reason for the numerous approaches to control found in the vast array of MRSA literature. MRSA continues to be a challenge of the 1990s. It appears to be an increasing problem in US hospitals, regardless of hospital size. Although its elusive behavior evades the most comprehensive and carefully planned control programs of even the most skilled hospital epidemiologists, hospitals continue to struggle for control of this organism. The alternative to control is probable resistance to vancomycin, which would have devastating public health consequences, particularly as alternative antibiotic therapy is not yet available. PMID- 8367330 TI - Infection control in oncology patients. AB - In conclusion, the nurse caring for the patient with cancer must be acutely aware of the risk of infection. Many interventions are used in attempts to minimize or prevent infection. Once the patient becomes neutropenic, the risk of life threatening infection increases dramatically. All nursing care is focused on treating infection and supporting the patient until bone marrow function returns. PMID- 8367331 TI - Respiratory syncytial virus. AB - A great deal of medical research and subsequent literature has been devoted to understanding and defining RSV as a dangerous respiratory pathogen. Careful assessment and preventative measures are the hallmarks of nursing care for the infants or young children with RSV. Acknowledging this seasonal virus and recognizing its potential effects, particularly on children and their families, is fundamental to the provision of effective pediatric health care. This appreciation is imperative in creating an environment focused on the containment of community-acquired RSV infections and the prevention of its nosocomial transmission. Additional research may someday allow us a greater understanding of the immune response to RSV, provide effective and safe antiviral agents, and yield vaccines to prevent primary and subsequent RSV infections. In the interim, however, we must apply our current knowledge and available tools to minimize RSV's destructive effects. Consistent use of basic infection control disciplines, such as appropriate handwashing, early identification of infected patients, careful placement of RSV-infected patients, and protective placement of high-risk patients, is necessary to prevent the nosocomial spread of this disease. In addition, policies restricting visitors with respiratory infections and prudent assignment of health care workers with respiratory infections need to be established and fully implemented. Strict and consistent compliance with these procedures will significantly decrease the incidence of RSV disease and subsequent morbidity and mortality in the pediatric population. PMID- 8367332 TI - Infection control and the pregnant health care worker. AB - Health care workers are constantly exposed to infectious agents in the course of their work. The pregnant health care worker presents additional concerns because of the potential risk of transmission of infection to the developing fetus. This article addresses the aspects of infection transmission, infectious agents of concern to health care workers, and operational aspects of an infection control program that is comprehensive, scientifically based, and equitable to all employees. PMID- 8367333 TI - Sterilization processes. Meeting the demands of today's health care technology. AB - Universal Precautions dictate sterilization for all invasive equipment that break the blood barrier; however, current methods of sterilization, such as steam and ethylene oxide gas (ETO), are not compatible with many of the delicate, heat sensitive surgical instruments used in modern health care. In addition, traditional sterilization methods are often too time consuming for practical use in the operating room. Clearly, new sterilization processes need to be developed. In this article, the criteria modern sterilization processes must meet and how some manufacturers plan to meet this challenge are discussed. In addition, the pros and cons of using peracetic acid (the newest sterilization process currently available) are examined. PMID- 8367334 TI - Reuse of single-use devices. A program model. AB - There are very few products that could be considered acceptable candidates for a reuse program when using this criteria for reuse. In addition, the cost of the resources necessary to implement and maintain an effective reuse program rarely equate to cost savings. In today's health care environment, the focus on employee safety adds another variable that may make reprocessing unacceptable. PMID- 8367335 TI - Stemming the tide of disreputable science: implications for nursing. AB - Numerous cases of fraud and misconduct in scientific endeavors have been brought to the attention of the public in recent years. Although nursing has not yet been scathed by abuses, the possibility exists that similar incidents can occur. The author reviews the factors that potentiate unethical practices and details a proactive approach for nursing to take to stem the tide of disreputable science. PMID- 8367336 TI - The view from Scutari: a look at contemporary nursing. AB - Modern nursing and healthcare delivery are examined from a unique vantage point provided by the author's visit to Scutari, Turkey. In Selimiye Army Barracks at Scutari, Florence Nightingale lived while directing the care of thousands of wounded British soldiers during the Crimean War. What was Nightingale's legacy to nursing, and what have nurses done with it? If Miss Nightingale were at her desk reading a status report on 20th-century nursing, what reactions would she have? What wars are engaging contemporary nursing? The author contends that Nightingale's vision can inspire us to move forward as a profession. PMID- 8367338 TI - Loose authorship. PMID- 8367337 TI - A glance back in time. Nursing diagnosis: process and decision. 1966. PMID- 8367339 TI - Toward understanding the self. AB - Others may know "me" but only "I" am the knower of myself. The metaparadigm of nursing includes four concepts: health, environment, nurse, and person. Each concept is complex and can be interpreted in diverse ways. The concept analysis in this article focuses on one aspect of person, specifically "self:" its birth, development, and loss. The author makes suggestions for using the analysis in nursing education, theory development, and clinical practice in caring for and promoting the health of individuals, groups, and families. PMID- 8367340 TI - One step forward and two steps back. PMID- 8367341 TI - Reader comments on recent article. PMID- 8367344 TI - Return-to-work experiences of people with cancer. AB - Maintaining employment after a cancer diagnosis and even during therapy is becoming a major challenge for an increasing number of individuals. The purpose of this study was to further understanding of the experience of returning to work after a cancer diagnosis by discovering the nature and processes of the experience's dimensions. This exploratory, longitudinal study systematically analyzed the dimensions of the return-to-work experience that were evident in data from 19 unstructured interviews. Grounded theory methods of study design and constant comparative analysis guided the interviews and data analysis. The core social process suggested by the data is one of mobilizing social support in the work environment. The inceptive theory explains and delineates steps in a process that ultimately facilitates a person's reintegration of normal activities after a cancer diagnosis. The added understanding available in these results can guide nurses to focus not only on related dimensions of the return-to-work experience, such as time off for treatment, but on central concerns, such as the social benefits of returning to work. PMID- 8367342 TI - An odyssey into biologic therapy. PMID- 8367343 TI - Predictors of self-care: a test of Orem's model. AB - Despite advancements in self-care for people with cancer, a profile of individuals who perform self-care behaviors has not been determined. Without these data, interventions cannot be targeted to specific patient groups that demonstrate the most need. This study's investigators used Orem's model of self care to determine predictors of self-care behavior. The sample consisted of 127 adults with cancer who were to receive their first dose of chemotherapy (e.g., doxorubicin, methotrexate, 5-fluorouracil, cyclophosphamide, or cisplatin, given alone or in combination). Data were collected from the subjects prior to the first cycle and at drug nadir for each of the four chemotherapy cycles. Potential predictors of self-care included demographic variables, performance status, affective state, social support, ability to manage a situation, self-care ability, and prior health-promoting activities. Self-care was measured using a 40 item behavior checklist. Multiple regression techniques were used to obtain four significant predictors of self-care, which accounted for 47% of the variance. Subjects with lower performance status, higher anxiety, less social support, and more education performed more self-care. These findings clarify Orem's model with this clinical population and provide a patient profile of self-care for practice. PMID- 8367345 TI - Managing cancer pain at home: the decisions and ethical conflicts of patients, family caregivers, and homecare nurses. AB - The purpose of this paper is to present findings from an exploratory, descriptive study that investigated the experience of managing pain in the home from the perspectives of the patient, the primary family caregiver, and the homecare nurse. In particular, the decisions and ethical conflicts encountered by members of 10 patient-caregiver-nurse triads were studied. Data were collected through in depth semistructured interviews, and the transcribed interviews were content analyzed by a multidisciplinary research team. Subjects reported that the use of medications prompted the majority of the decisions and provoked most of the conflicts; however, decisions related to assessment, the future, and how to live with pain were identified as well. Subjects also identified other areas that created conflict, such as spiritual/theological issues, when to tell the truth, and interpersonal relationships. Findings illustrate the importance of understanding the beliefs and values that influence individuals' decisions and conflicts, because discrepant perceptions of the pain experience among patients, caregivers, and nurses can interfere with satisfactory management of pain. PMID- 8367346 TI - Pathophysiology of hypokalemia in patients with cancer: implications for nurses. AB - Hypokalemia is a potentially life-threatening complication that occurs in many patients with cancer. Nurses need to be aware of the many common causes of this electrolyte disorder as well as appropriate assessment strategies that will enable potential problems to be detected and treated early. This article begins with a review of normal potassium balance and physiology, followed by a discussion of potential causes of hypokalemia in patients with cancer. These causes are grouped into four categories: inadequate dietary intake, extrarenal losses, redistribution abnormalities, and renal losses. Common causes of hypokalemia in patients with cancer are illustrated with case examples. Signs and symptoms associated with hypokalemia are discussed. Finally, implications for nursing assessment and intervention related to the administration of potassium are reviewed. PMID- 8367347 TI - Bridging the gap between research and clinical practice: a collaborative approach. AB - In nursing, a gap sometimes exists between research and practice. This paper discusses how a group of 11 nurses successfully bridged this gap. The group was composed of nurses from a large teaching hospital, a regional outpatient cancer center, and a university. The result of the group's work over a two-year period was an externally funded research proposal. This paper discusses the strategies that led to the group's success and provides specific recommendations for nurses who want to form similar groups. PMID- 8367349 TI - "Humor book" provides release for nurses. PMID- 8367350 TI - Special motto enforces the importance of humor and hugs. PMID- 8367348 TI - Role modeling: an educational strategy to promote effective cancer pain management. AB - Successful pain management is a crucial element in the nursing care of the patient with cancer. Among the many problems underlying poorly managed pain, one prominent concern is healthcare professionals' lack of current knowledge. Although educational programs are an established method of increasing knowledge, specific programming strategies may have a more significant impact on knowledge retention. This quasiexperimental study used role modeling as an educational method to improve knowledge retention. A purposive sample of 20 RNs participated in an educational program in which a lecture-only format was used for the control group and a lecture format plus a role-modeling component was used for the experimental group. An oncology pain management assessment tool was administered in a pretest/post-test design with repeated measures. A one-tailed t-test for gain scores was used to test the hypothesis. Mean change scores between groups were similar. Future studies are needed to further analyze the impact of role modeling on similarly matched, but larger, groups. PMID- 8367351 TI - Unit offers unique and fun approaches to therapy. PMID- 8367352 TI - Humor helps to "break the ice" during patient education. PMID- 8367353 TI - Management of children with epiglottitis during transport: analysis of a survey. AB - Because nationally accepted guidelines for the management of children with epiglottitis during transport have not been published, we surveyed physicians attending the 1990 Pediatric Critical Care Transport Leadership Conference in order to delineate current practices and to test for correlations between complications and methods of management. A 22-item questionnaire was distributed, addressing demographics, availability and composition of a designated transport team, methods of airway management, use of medications for sedation or paralysis, monitoring techniques, and complications encountered during transport. Forty three of the 49 attendees completed the questionnaire (87.8%). Almost all were attending physicians (60.9% pediatric intensivists, 29.3% pediatric emergency physicians) practicing in tertiary care facilities (58.5% in children's hospitals, 41.5% in general hospitals). Eighty-three percent of centers had designated transport teams. For transfer of a child with suspected epiglottitis from a physician's office, virtually all respondents recommended transport by ambulance, 64% to the nearest facility and 36% directly to a tertiary care center. Regarding interhospital transfers, 49% recommended intubation prior to transport in all cases, whereas 49% considered it on an individual basis. The majority of respondents preferred nasal intubation. To prevent dislocation of the endotracheal tube, 79.1% recommended taping it to the face only (as opposed to around the skull), 70.7% administered paralytic agents, but only 35.2% used additional mechanical restraints.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367354 TI - Carbamazepine poisoning in children. AB - Carbamazepine poisoning in children remains a significant problem for the emergency physician. We report 16 cases of toxicity at British Columbia Children's Hospital and discuss presenting symptoms, treatment, and hospital course. Pharmacology, drug interactions, resulting in carbamazepine toxicity, and treatment guidelines are summarized. PMID- 8367355 TI - Skin disorders encountered in a pediatric emergency department. AB - A total of 1381 visits to a pediatric emergency department (ED) during a six-week period were surveyed to determine the types and frequency of skin disorders encountered. A primary skin complaint accounted for 431 (31%) visits. There was a skin complaint of secondary importance in another 35 (3%) visits, and a skin disorder not mentioned by the patient or parent was detected on examination in a further 88 (6%) visits. In total, 554 (40%) visits included a skin complaint or a skin finding. As expected, cutaneous trauma (including abrasions, contusions, lacerations, and burns) accounted for a substantial number of visits, but a wide range of other dermatologic conditions was also represented, including skin infections, contact dermatitis, and numerous other disorders. Skin diseases are encountered frequently in the pediatric ED setting and should be included in the formal teaching curriculum for training programs in pediatrics and emergency medicine. PMID- 8367356 TI - Acute urinary retention in children. AB - Acute urinary retention (AUR) is an uncommon diagnosis in childhood, associated with a variety of causes. The emergency physician is often the first to be called upon to evaluate and treat these children. To assist in making the diagnosis, we present our five-year experience with AUR presenting to the pediatric urology service, often through the pediatric emergency department. We present and discuss examples of not only the common reasons for AUR but also uncommon diagnoses and, in two cases, etiologies for retention we believe have not been previously described in the pediatric literature. PMID- 8367357 TI - Use of the transmitter-receiver metal detector in the evaluation of pediatric coin ingestions. PMID- 8367358 TI - Traumatic pneumomediastinum in a child secondary to corn chip perforation of the esophagus. AB - Esophageal perforations, while an infrequent form of trauma in the pediatric population, are of concern because of their life-threatening complications. If not recognized and treated promptly, esophageal injuries can result in mediastinitis and death. An unusual case is presented, describing traumatic esophageal perforation in a child resulting from laceration by an ingested corn chip. A study is reported investigating the rigidity of three types of these popular snack chips. Stress testing and statistical analysis of the resultant measurement data indicated that the three brands of chips were equally rigid. The mean force of compression required to fracture the chips was approximately three pounds, a force great enough to damage the fragile structures of the upper aerodigestive system. Physicians and parents alike should be aware of the possible dangers of this type of snack food to avert the possibility of esophageal injury with its resultant morbidity and potential mortality. PMID- 8367359 TI - Pseudodisaster: a case of mass hysteria involving 19 schoolchildren. AB - A case of mass hysteria involving 19 children has been presented. Our case demonstrated many of the common symptoms and vectors identified in the literature. No children were harmed, but significant health care dollars were spent ensuring their safety. Better education of child care personnel and preplanning by schools may reduce the frequency of this condition. PMID- 8367360 TI - Pertussis: the return of a bad penny. AB - We describe two related cases of pertussis infection ("whooping cough"). This disease entity was almost completely eradicated through successful mass immunization programs. In the past decade it has demonstrated a steady rise in incidence. The epidemiology, clinical manifestations, treatment, and current vaccines for pertussis infection are reviewed. PMID- 8367361 TI - Acute gastric volvulus in children: a rare disorder. AB - A case of acute gastric volvulus has been presented. Although this disorder can occur in a chronic intermittent fashion, the potentially catastrophic acute form should be diagnosed early and surgically corrected. Careful attention to presenting signs and a high index of suspicion lead to prompt recognition and treatment. PMID- 8367362 TI - Button battery ingestions in children. PMID- 8367364 TI - A 13 year old with desipramine ingestion. PMID- 8367363 TI - Coping with physician payment reform: what is it, and why should pediatric emergency physicians care? PMID- 8367365 TI - Apnea and cyanosis in an infant. PMID- 8367366 TI - Carbon dioxide monitors: exhaled gas (capnographs, capnometers, end-tidal CO2 monitors). PMID- 8367367 TI - Laceration management. PMID- 8367368 TI - Case 03-1993: a 20-month-old boy with fever and neck stiffness. PMID- 8367369 TI - [The opening of potassium channels as a new trend of pharmacologic treatment of coronary disease in light of endothelial mechanisms of hemodynamic regulation]. PMID- 8367371 TI - [The composition of fatty acids in individual classes of blood platelet phospholipids of patients with uremia]. AB - The most important role in the formation of defects of the haemostasis in patients with uraemia is attributed to disorders of platelet activation. The important elements of phospholipid structure are saturated and unsaturated fatty acids. Five classes of phospholipids were identified in the platelets: phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylcholine (PC) and sphingomyelin (Sph). This paper aimed at the assessment of the fatty acid composition in individual classes of phospholipids of blood platelets in patient with uraemia. We studied 18 uraemic patients who were treated conventionally and 21 patients treated with with repeated haemodialysis. The classes of phospholipids were isolated by thin layer chromatography and the contents of fatty acids in the individual classes of of phospholipids were assessed by gas chromatography. In patients treated conventionally great differences in the contents of fatty acids in the individual classes of phospholipids were demonstrated as compared with the control group. The differences can be caused by disorders of blood plasma lipids. In general- more unsaturated fatty acids were found in the classes of phospholipids forming the outer surface of the platelets as compared to the inner surface. In haemodialysed patients the differences in the fatty acid contents compared with the control group were evidently smaller (perhaps resulting from some normalization of biochemical changes in the plasma of dialyzed patients). In this group a greater content of unsaturated fatty acids in Sph and PC was also found. The high content of unsaturated fatty acids may increase the platelet membrane fluidity and intensive lipid-protein reaction, e.g. binding of coagulation factors, so may play a role in haemostasis disturbances observed in uraemic patients. PMID- 8367370 TI - [Level of zinc, copper, selenium and nickel in serum of patients treated for chronic renal failure with hemodialysis--influence of erythropoietin therapy]. AB - 52 patients with chronic renal failure treated with haemodialysis and 21 healthy subjects were observed. All patients were divided in 2 groups: 1. erythropoietin treated patients (+EPO), 2. patients not treated with erythropoietin (-EPO). In all patients immediately before dialysis and after dialysis the blood samples were withdrawn for estimation of creatinine, haemoglobin concentration, haematocrit value and zinc, copper, selenium, and nickel concentration. In healthy subjects such measurements we made only once. In all patients serum zinc, selenium and nickel concentrations were significantly lower than in normals. Copper concentration was insignificantly higher in normals than in patients with CRF. No significant differences were found in serum concentration of zinc, copper, selenium and nickel between +EPO and -EPO. During haemodialysis a decrease of serum zinc, copper and selenium levels in all examined group was seen. No significant changes between serum, zinc, selenium, copper and nickel concentration between patients treated with erythropoietin and without erythropoietin. Conclusions 1. Serum zinc, selenium and nickel concentration were significantly lower in patients treated with haemodialysis than in normals. 2. Serum concentration of zinc, copper and selenium decreased during haemodialysis. 3. Probably erythropoietin therapy does not influence serum zinc, selenium, copper and nickel levels in patients with chronic renal failure. PMID- 8367373 TI - [Cardiac arrhythmias during extracorporeal shock wave lithotripsy]. AB - Holter monitoring was performed in 55 patients (24 women, 31 men), mean age 50.7 +/- 11.3 who underwent ECG-triggered extracorporeal shock wave lithotripsy (ESWL). Patients were divided into two groups A--30 with history of cardiac disease and B--25 control. The heart rate was significantly higher before and after ESWL in the first group. The number of premature ventricular contractions was higher during ESWL in the same group. No other cardiac complication was observed. PMID- 8367372 TI - [Estimation of selected markers of bone metabolism inpatients with nephrolithiasis]. AB - 19 patients with active nephrolithiasis, 14 patients with non-active nephrolithiasis and 17 healthy subjects were examined. After 7 days consumption of standardized low calcium, low phosphate, low purine and low protein diet, plasma parathyroid hormone (PTH) and osteocalcin concentration, activity of the alkaline phosphatase and its bone fraction were assessed before and after 4 hours i.v. infusion of calcium gluconate (15 mg/kg b.w. in 500 ml 0.9% NaCl). In addition, urinary excretion of oxalate, calcium, phosphate and magnesium were estimated in all examined groups. CONCLUSIONS: 1. In comparison to healthy subjects, patients with nephrolithiasis are characterized by higher plasma PTH and osteocalcin concentration, increased activity of bone fraction of alkaline phosphatase and urinary oxalate and calcium excretion. 2. Disturbances of calcium phosphate and oxalate metabolism, PTH secretion and bone osteoblastic activity found in patients with active nephrolithiasis are qualitatively similar but quantitatively more intensive than in patients with non-active nephrolithiasis. PMID- 8367374 TI - [Efficacy of hepatitis B vaccine after intramuscular or intradermal administration]. AB - We compared the efficacy of intramuscular (im) and intradermal (id) administration of vaccine against HBV. Only one out of 25 im vaccinated subjects did not respond whereas all 25 id immunized persons developed anti-HBs above 10 IU/l. The mean serum level of anti-HBs in im and id vaccinated group was 2351 +/- 2358 IU/l and 1823 +/- 1502 IU/l, respectively (p = 0, 382; NS). It seems that the efficacy of both vaccine administration is very similar. PMID- 8367375 TI - [Acute failure of transplanted kidney after administration of angiotensin converting enzyme inhibitors (iACE)]. AB - Treatment of kidney transplant recipients with inhibitors of angiotensin converting enzyme (iACE) is associated with increased risk of deterioration of renal function. Between 1988-1992 in Transplantation Institute, 71 renal allograft recipients were treated with iACE. 44 of them received iACE in order to reduce proteinuria, 18 due to secondary polycythemia and 9 recipients received iACE because of hypertension resistant to at least 3 hypotensive drugs. Acute renal failure developed in 5 patients and all of them received iACE as treatment of resistant hypertension. After resumption of renal function, in 3 of 5 patients artery stenosis of the transplanted kidney was found. In 1 recipient acute renal failure occurred despite normal renal arteriography and normal indexes of the flow through renal arteries determined by Doppler ultrasound examination. In 2 patients acute renal failure appeared after a single minimal dose of iACE. Severe arterial hypertension in patients with transplanted kidney is a particular risk factor for development of acute renal failure after iACE. The normal arteriography in transplanted kidney and normal arterial blood flow measured by means of Doppler ultrasound do not exclude the possibility of development of acute renal failure after iACE. PMID- 8367376 TI - [Kidneys and hypertension]. PMID- 8367377 TI - [Possibilities and perspectives of genetic engineering in management of genetic diseases, neoplasms and AIDS]. PMID- 8367378 TI - [New approaches for treating skin necrosis in protein C deficiency]. AB - A 62-year-old woman with a 8-month-history of recurrent deep and superficial vein thrombosis developed multiple areas of skin necrosis during warfarin treatment initiation. Routine coagulation tests did not revealed any abnormalities. Protein C plasma activity and concentration were significantly decreased (59.9% and 63.3% of the normal value, respectively). Antithrombin III and protein S (total and free) content were in the normal range. Initially, the adjusted dosage of standard heparin and fresh frozen plasma was administered. Thereafter, the treatment with low doses of oral anticoagulant (acenocoumarol) was reinstalled simultaneously with Protein C Concentrate (Immuno, Vienna) intravenous administration. After six days of the oral anticoagulation the therapeutic value of prothrombin time was obtained and administration of Protein C Concentrate could have been discontinued. No adverse reactions and post-transfusions complications were observed. PMID- 8367380 TI - Effect of DL alpha-lipoic acid on tissue lipid peroxidation and antioxidant systems in normal and glycollate treated rats. AB - The cytoprotective activity of alpha-lipoic acid against free radical toxicity, manifested during experimental hyperoxaluria, has been investigated. Glycollate was used as the inducer of oxalate hyperoxaluria in rats. The increase in lipid peroxidation and superoxide dismutase (SOD) activity, associated with a decrease in catalase activity and glutathione (GSH) level, are the salient features observed in tissues of hyperoxaluric rats. Free radical toxicity in the glycollate fed rats is effectively counteracted by lipoic acid administration. Lipoic acid administration brought about a significant decrease in peroxidative levels with an increase in catalase activity and glutathione level. These observations highlight the antioxidant property of alpha-lipoic acid and its cytoprotective action against experimental hyperoxaluria. PMID- 8367379 TI - Effect of the nifedipine-atenolol association on arterial myocyte migration and proliferation. AB - The in vitro effect of nifedipine and atenolol, either alone or in combination, on the proliferation and migration of rat aortic smooth muscle cells was investigated. Nifedipine inhibited the replication of arterial myocytes in concentrations ranging between 10 and 100 microM. The inhibition, evaluated as cell number, was dose- and time-dependent with an IC50 of 39 and 34 microM after 48 and 72 h, respectively; the cell doubling time increased with drug concentrations up to 118 h versus 28 h for controls. Atenolol alone failed to reduce arterial myocyte proliferation, and did not influence the effect of nifedipine on cell proliferation. Nifedipine and atenolol alone inhibited in a dose-dependent manner rat aortic myocytes migration induced by fibrinogen as chemotactic agent. When the combination nifedipine-atenolol was investigated, an additive inhibitory effect on cell migration was observed. These results provide in vitro support for a potential effect of this drug association on early steps of atherogenesis. PMID- 8367381 TI - Anti-inflammatory activity of newly synthesized 2,6-bis-(1,1-dimethylethyl)phenol derivatives. AB - Four new 2,6-bis-(1,1-dimethylethyl)phenol derivatives were synthesized and evaluated for their anti-inflammatory activity, in comparison with indomethacin and vitamin E, using the carrageenan paw oedema assay in rats. Among the tested compounds, the 4-(6,7-dichloro-4H-1,2,4-benzothiadiazine-3-yl)-2,6-bis-(1,1- dimethylethyl)-phenol-S,S-dioxide (4) was the most active compound markedly reducing oedema formation. Moreover compound 4 potentiated, particularly in the early phase of carrageenan paw swelling (2-4 h), the antiphlogistic effect of indomethacin. This compound, on the other hand, did not show ulcerogenic activity at therapeutic doses and did not potentiate the gastric damage induced by high doses of indomethacin. In vitro, the studied compounds (1-4) showed to be moderately active as scavengers of 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazil, 4 being the most active among them. Compound 4, on the contrary, was practically inactive on liposome peroxidation where compounds 1, 2, 3, which are modest anti inflammatory agents, exerted a good or moderate effect. PMID- 8367382 TI - Dexamethasone modulation of gestation length and parturition in rats. AB - Dexamethasone blocks aromatase and phospholipase A2 enzyme activities that are essentially involved in the formation of oestrogens and prostaglandins, the key chemicals to initiate parturition. The present study was undertaken to determine whether dexamethasone, a potent glucocorticoid, could prolong gestation and/or delay parturition in rats. Dexamethasone at 0.5 mg/rat/day from Day 19 through Day 21 of pregnancy consistently prolonged gestation. Only 36% of the pregnant rats had labour with an extended parturition time. Foetal mortality rate was also high. The remaining 64% pregnant rats that did not deliver showed intrauterine foetal death and resorption. Concomitant injection of oestradiol cyclopentylpropionate or prostaglandin F2 alpha on Day 19 effectively reversed the deleterious effects of dexamethasone. 100% of the pregnant rats had successful labour at term. The parturition time and foetal mortality rate were not different from controls. The results, therefore, indicate that an excess glucocorticoid that initiates parturition in sheep conversely prolongs gestation and delays parturition in rats. PMID- 8367383 TI - [Possibilities of modern toxicologic analysis for determining cause of death]. PMID- 8367385 TI - [Individualization and identification of cadaver parts dismembered by contact with the ship propellor using DNA technology]. PMID- 8367384 TI - [The number of autopsies at the Chemnitz Institute of Pathology before and after unification (1987-1992)]. AB - The numbers of autopsies performed at the Institute of Pathology in Chemnitz before and after German unification (1990) were compared (1987-1992). In 1991 and 1992 a decrease of up to 40% was observed. In the former GDR an autopsy was possible without agreement of the relatives, whereas since unification the relatives have the power to forbid an autopsy. This was the principal reason for the dramatic decline in the past 2 years. Another relevant factor is the difficult economic situation of most hospitals in the region, preventing the arrangement of more autopsies. Analysis also shows the important role of physicians in clinics regarding the autopsy rates. PMID- 8367386 TI - [Pneumatosis intestinalis--histology, immunocytochemistry and new theory of morphogenesis]. AB - Based on the light microscopical and immunocytochemical findings in two cases of pneumatosis intestinalis, a new theory is advanced on the morphogenesis of the cysts that can be observed in this disease. The cavities identifiable in both cases in the submucosa of the small intestine and of the colon, respectively, were partially lined by histiocytes and foreign-body giant cells. Most of the lumina found in the subserosa of the stomach, small intestine and colon had an identical aspect. In addition, there were numerous true cysts here with a narrow, single-layered cells seam, showing the immunocytochemical characteristics of the mesothelium, but not the capillary endothelia. Thus, contrary to previous assumptions, pneumatosis interstinalis apparently does not develop from cystic dilatation of gas-filled lymph vessels that shrink and disappear in the process of an inflammatory foreign body reaction. Rather, the disease initially seems to manifest itself through gas-filled pseudocysts partially bordered by histiocytes and foreign-body giant cells, which become secondarily mesothelialized in the subserosa. Lymph vessels would thus not have significance for the morphogenesis of this disease. PMID- 8367387 TI - [Genetic-morphologic fatal syndromes. Fetal akinesia sequence (Pena-Shokeir syndrome I)]. PMID- 8367389 TI - [Genetic-morphologic fatal syndromes. Bowen-Conradi syndrome]. PMID- 8367388 TI - [Genetic-morphologic fatal syndromes. Cerebro-oculo-facioskeletal syndrome (Pena Shokeir syndrome II)]. PMID- 8367390 TI - [Tungiasis--a middle European rare skin parasitosis. A case report]. PMID- 8367391 TI - [Rupture of an echinococcus cyst in the heart septum as a cause of sudden heart death]. PMID- 8367393 TI - Special issue on virus separation and purification methods. PMID- 8367392 TI - [Awarded the honorary chair for anatomy in Halle 100 years ago: Carl Joseph Eberth--discoverer of the typhus pathogen]. PMID- 8367394 TI - Purification of viruses by electrophoresis in sucrose concentration gradients. 1972. AB - Zone electrophoresis (ZE) in concentration gradients of sucrose proved to be a powerful technique in the purification of viruses although it is seldomly used as a single step for the separation of the infective agent from extraneous matter but usually as a final procedure. No difficulties were experienced in the purification of plant viruses with ZE possibly because of the resistance of the agents to the chloroform butanol treatment which the impure plant viruses received prior to the ZE. Likewise no difficulties were encountered during purification of human and animal picorna viruses because they also are resistant to chloroform or chloroform-butanol treatment prior to ZE. Purification of animal and possibly human reoviridae ZE as a final step is involved as they are associated with or even attached to the host cell membranes which are lipoidal in nature. Because the lipoidal material on the virus has an affinity for organic solvents the virus particles are caught in the emulsion when an extract of the crude virus material is shaken with the organic solvent. With these viruses polyethylene glycol M(r) 6000 (PEG) is often helpful as a means of displacing most of the host proteins as a step in the partial purification prior to ZE. Neurotropic African horse sickness virus which presented many problems to overcome was rendered free of extraneous proteins to the extent that electron micrographs could be made of it. Neurotropic Rift Valley fever virus was similarly difficult to purify as it was always associated with mouse brain components. This virus was finally purified from infected mouse blood in which the virus particles were not associated with host cell debris and other extraneous proteins. Zone electrophoresis experiments were not conducted on viruses with large particle sizes e.g. myxoviruses because they could be purified without a great deal of effort using polymer displacement, and thin layer centrifugation. Zone electrophoresis as a means of final purification was vividly displayed with the purification of five viruses of the larvae of the pine emperor moth, Nudaurelia cytheria cytheria. PMID- 8367395 TI - Tube inserts as aids in preparative ultracentrifugation. 1983. PMID- 8367396 TI - Bead centrifuge tube inserts--a semi-quantitative theory. 1984. PMID- 8367397 TI - Purification of viruses by centrifugation in gradients of inert substances. AB - By using a reorienting gradient centrifuge rotor cut from a block of Nylon and fitted with eight septae, it was possible to separate the components of the haemolymph of the mollusc Turbo sarmaticus into three fractions in a sucrose gradient held in the bowl of the rotor. The fractions were (108 and 98)S, 44S and 16-22S. The success of the experiment was due to the large differences in the sedimentation coefficients of the components. When the rotor was applied to the natural mixture of the five viruses of the caterpillars of Nudaurelia cytheria only the main component could be isolated in a pure state. The viruses were separated by isopycnic centrifugation in "self formed" caesium chloride gradients, using a Beckman Model E analytical centrifuge in which a separation cell fitted with a centerpiece with two perforated partitions was used. PMID- 8367398 TI - Purification and aggregation of influenza virus by precipitation with polyethylene glycol. 1974. PMID- 8367399 TI - Isolation of a cytoplasmic polyhedrosis virus by physical and immunological techniques. 1975. PMID- 8367400 TI - Purification of filamentous plant viruses by thin layer centrifugation (applied to TMV, SCMV, PVX, SCV and YMC viruses). 1975. PMID- 8367401 TI - Electro-extraction of viruses from infected plant tissue (applied to turnip yellow mosaic, tobacco mosaic and maize streak viruses). 1981. PMID- 8367402 TI - Purification of potato leaf roll virus. PMID- 8367403 TI - Purification of PVYo and its soluble antigen by physico chemical means. AB - Potato virus Yo was purified by centrifugation of infected and minced plant tissue in the virus extraction rotor. As the initial seeding material was heavily contaminated with tobacco mosaic virus (TMV) this virus was isolated and antibody was elicited in chickens. The chicken antibody (IgY) against TMV was used for removing this extraneous virus from the original PVYo seeding material prior to propagating PVYo in tobacco plants, CV Glutinosa. PMID- 8367404 TI - Isolation of viruses by electro-extraction of infected plants. 1977. PMID- 8367405 TI - Preparative immunoabsorption electrophoresis. 1978. PMID- 8367407 TI - Concentration of solutes by freezing and centrifugation. PMID- 8367406 TI - An insert for the reorienting gradient rotor for virus extraction from infected plants. 1979. PMID- 8367408 TI - The sedimenting-droplet procedure for measuring fluid densities. 1980. PMID- 8367409 TI - Determination of the number of Fab1 pieces which react with high molecular weight antigens. 1982. PMID- 8367410 TI - Cytokine networking in the placenta. PMID- 8367411 TI - Differential gene expression in the amnion, chorion, and trophoblast of the human placenta. AB - Human chorionic gonadotrophin (hCG), placental alkaline phosphatase (PLAP), and pregnancy-specific glycoprotein (PSG) are three major proteins produced by the trophoblast of the human placenta. Immunocytochemical studies suggest that PSG and hCG are also present in the human amnion. In this study, we examined whether amniotic and chorionic membranes were capable of expressing trophoblastic specific genes. As previously reported, trophoblasts express high levels of hCG beta, hCG alpha, PLAP, and PSG. Both amnion and chorion were found to express PLAP and hCG beta mRNA. However, the hCG alpha transcript was expressed only by the amnion, but not by the chorion in the term placenta. Recent molecular cloning studies indicate that human PSGs are a group of closely related placental proteins that, together with the carcinoembryonic antigen family members, comprise a subfamily within the immunoglobulin superfamily. To demonstrate that amnion and chorion also express PSG transcripts, we employed ribonuclease protection analysis using probes specific to the 5' and 3' region of PSG mRNAs. Our data indicate that while amniotic as well as chorionic membrane expressed low levels of the PSG genes, only a certain subpopulation of PSG transcripts were expressed. Furthermore, the amnion and chorion demonstrated differences in PSG species expression from each other and from trophoblastic tissue. Thus, human amnion, chorion and trophoblast selectively express several placental genes. PMID- 8367412 TI - Differences in binding characteristics of rat and human transferrin by rat visceral yolk sac placenta. AB - Previous work has shown that human serum supplemented with rat transferrin can support the normal growth of cultured rat conceptuses, but that supplementation with human transferrin has no such effect. Such results strongly suggest an hypothesis of species-specificity. This potential specificity was therefore investigated by comparing uptake, binding, competition and vectorial transport of both rat and human transferrin using two well-established systems, those of 17.5 day rat visceral yolk sacs and anembryonic yolk sacs in culture. The results of these investigations show that human transferrin displays a lower rate of uptake and lower binding affinity for the rat transferrin receptor than does rat transferrin. Human transferrin competes poorly with rat transferrin for receptor occupancy unless present in 20-fold excess. Both molecules are taken up by receptor-mediated endocytosis and are processed in a similar manner. Anembryonic yolk sac experiments show that a greater proportion of intact rat transferrin is transported to the exocoelomic fluid than is intact human transferrin. Binding analyses show a difference in binding affinities of the two molecules for the rat transferrin receptor and also that human transferrin exhibits negative cooperativity in its binding. This evidence strongly supports an hypothesis of species-specificity in the binding of transferrin to the transferrin receptor in the rat visceral yolk sac. PMID- 8367413 TI - Respiratory control induced by ATP in human term placental mitochondria. AB - Oxygen uptake in human placental mitochondria was stimulated by ATP addition. ATP induced respiration was supported by malate, alpha-keto glutarate, and succinate, and inhibited by oligomycin and carboxytractyloside. This phenomenon was not caused by contamination with unspecific phosphatases or alkaline phosphatase, since NaF, L-phenyl alanine, or P1, P5-di-(adenosine-5') pentaphosphate failed to inhibit oxygen uptake induced by ATP. The stimulation of respiration was caused by an ATPase activity tightly bound to mitochondria, which yields ADP that is responsible for the oxygen uptake. The stimulation was not an uncoupling effect because ATP addition produced a transition between state 3 and 4 of respiration, indicating that ATP was not released from mitochondria. PMID- 8367415 TI - Short report: cytokine production by human fetal membranes and uterine decidua at term gestation in relation to labour. PMID- 8367416 TI - [Screening for breast cancer. Achievements and controversies]. PMID- 8367414 TI - Effect of exogenous arachidonic acid and enzyme inhibitors on placental prostanoid production. AB - Prostanoids play an important role throughout pregnancy and during the initiation and progress of labor. The human placenta, at term, produces large quantities of prostanoids, yet little is known of the rate-limiting steps regulating their biosynthesis. In these studies, the effect of exogenous arachidonic acid and of enzyme inhibitors on the release of placental prostanoids was investigated. Basal prostaglandin E (PGE), prostaglandin F (PGF), thromboxane (TxB2) and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) increased from the fifth hour in culture, yet the increased PGF release did not result in further 13,14-dihydro-15 keto-PGF2 alpha (PGFM) production. Addition of varying doses of arachidonic acid (0.2-10 micrograms/ml) had no significant effect on PGFM, TxB2 or 6-keto-PGF1 alpha, although the endogenous arachidonate was similar to or much less than the doses studied. Only at the 10 micrograms/ml dose was a delayed increase of PGE and PGF observed. Incubation with indomethacin resulted in an immediate inhibition of PGE, PGF, TxB2 and 6-keto-PGF1 alpha, with a delayed inhibition of PGFM. The phospholipase A2 inhibitor, quinacrine (10 microM), had no significant effect on PGE, PGFM, TxB2 or 6-keto-PGF1 alpha. PGF was inhibited within the first hour of quinacrine exposure, but no significant inhibition was observed thereafter. Ca2+ chelator, EDTA, effected an inhibition of only 6-keto-PGF1 alpha. Nordihydroguaiaretic acid, a leukotriene inhibitor, reduced PGE release as well as 6-keto-PGF1 alpha. These data demonstrate the high biosynthetic competence of the human term placenta to produce prostanoids. This capacity does not appear to be rate-limited by arachidonic acid availability. However, the metabolism of PGF to PGFM appears to be saturated. In addition, the production of placenta prostacyclin may be affected by Ca2+ levels, as chelating agent inhibited the release of 6-keto-PGF1 alpha. PMID- 8367417 TI - [Transplantation of reduced-size livers in children]. AB - Nowadays, liver reduction techniques make it possible to use livers obtained from adults or adolescents for implantation in children. These techniques have been evaluated by analysis of 100 liver transplantations performed between January 1988 and October 1991 in 85 children. Forty-six full-size grafts implanted in 38 children (group 1) were compared with 54 reduced-size grafts implanted in 47 children (group 2). The overall actuarial survival at 4 years was 86 percent. There was no statistical significant difference between the two groups as regards the rates of death (8 versus 19 percent), reoperation (54 versus 64 percent), retransplantation (15 versus 16 percent), hepatic artery thrombosis (13 versus 15 percent) and graft survival (82 versus 70 percent) respectively. Haemorrhage was significantly more frequent in group 1 than in group 2 (P = 0.04), irrespective of whether transplantation was performed urgently or electively. Using reduced size livers considerably increases the number of liver grafts available to children. Apart from a greater risk of haemorrhage, the results obtained with reduced-size livers were identical with those obtained with full-size livers. PMID- 8367418 TI - [Buerger disease, clinical and prognostic aspects. 83 cases]. AB - A retrospective analysis of 83 records of patients with Buerger's disease is presented. There were 71 men and 12 (14.5 percent) women. Compared with men, women with Buerger's disease had a significantly more frequent vasomotor disorder, but they had less trophic disorders and a lower risk of amputation. After a 42-month follow-up, it appeared that tobacco plays a major role in the prognosis: patients who continued to smoke had significantly more numerous acute episodes than those who ceased smoking. The degree of intoxication is an element of prognosis, but good medical management contributes to reduction in the number of major amputations: only 5 patients (6 percent), all male, had a leg (4 cases) or a thigh (1 case) amputated. PMID- 8367420 TI - [Treatments by local injections of botulinum toxin in neurology. Indications and results]. AB - Local injections of botulinum toxin constitute the only truly effective treatment of certain abnormal movements and focal dystonias. The authors describe its indications and report on their personal experience. One hundred and seventeen patients were treated: 48 for blepharospasm, 46 for hemifacial spasm and 23 for spasmodic torticollis. The results were evaluated by means of a score taking into account the effectiveness of treatment, the duration of this effectiveness, the side-effects, if any, observed, and the course of the neurological disorder after several series of injections. The results were good or excellent in 91 percent of patients with hemifacial spasm and 79 percent of patients with blepharospasm. Spasmodic torticollis was much improved in 35 percent of the cases and less, but satisfactorily, improved in 48 percent. In this disease, the muscles which antagonize those responsible for the dystonia must absolutely be re-educated. PMID- 8367419 TI - [Natural history of duodenal ulcer]. AB - The authors have studied the natural history of duodenal ulcer from published data, in an attempt to determine precisely the evolutive potential of this disease both spontaneously and during its treatment. They deal successively with the risk of complication and the short- or long-term influence of medical and surgical treatment on the occurrence of exacerbations and complications. The role played by Helicobacter pylori in healing of the ulcer and in the long-term course of the ulcerous disease, as well as the problems concerning its duration and mortality, are discussed. The data clearly show that the medical and surgical treatment of duodenal ulcer can slow down, at least temporarily, the course of the disease. Other studies are needed before drawing firm conclusions concerning the relationship between H. pylori and duodenal ulcer, even though numerous studies seem to have demonstrated that eradication of this micro-organism is associated with a substantial decrease in the risk of recurrent ulcer. PMID- 8367421 TI - [Cystic dystrophy and aberrant pancreas treated by gastroenterostomy]. PMID- 8367423 TI - [Diagnosis of leptospirosis, contribution of hemoculture. 11 cases]. PMID- 8367422 TI - [Immunologic changes in Steinert disease]. PMID- 8367424 TI - [Thrombopenia following treatment with omeprazole]. PMID- 8367425 TI - [Partial kinetic motor seizures in a 59-year-old man. A rare manifestation of diabetes]. PMID- 8367426 TI - [Cerebrovascular complications related to mitral stenosis]. PMID- 8367427 TI - [Disseminated anguilluliasis in HIV infection. A new case]. PMID- 8367428 TI - [Visceral leishmaniasis. Parasitological diagnosis by leukocyte concentration]. PMID- 8367429 TI - [Diagnosis of orthostatic hypotension. Value of the head-up tilt test. 110 cases]. PMID- 8367430 TI - [Incidence of primary respiratory lesions in the course of severe burns]. PMID- 8367431 TI - [Human polyvalent immunoglobulins: what is their value in thrombopenia in the course of leptospirosis?]. PMID- 8367432 TI - [Pancreatic somatostatinoma. A new case]. PMID- 8367433 TI - [Disseminated pneumocystosis. 3 cases in HIV seropositive patients]. PMID- 8367434 TI - [Improvement of lipid parameters in patients with heart transplantation after withdrawal of prednisolone]. PMID- 8367435 TI - [Munchausen syndrome: mimicking HIV infection]. PMID- 8367437 TI - [Role of peripheral vascular angioplasty]. PMID- 8367436 TI - [Strategy of vaccination against hepatitis A]. PMID- 8367438 TI - [Intracranial cavernoma. 30 cases]. AB - During the last few years, as a result of improved neurodiagnostic procedure there has been an increase in the number of intracranial cavernous angioma. We present 30 cases totalling 32 cavernous angiomas. Twenty-one received a successful surgical treatment. Twenty-four angiomas were supratentorial (75 percent) and 8 subtentorial (25 percent). Cavernous angiomas are congenital vascular malformations, usually of small size, with multiple vascular cavities surrounded by fibrous walls. They are often found in young adults (mean age 35 years in our series), most frequently located in the supratentorial white matter. The presenting symptoms were epilepsy, haemorrhage and an expanding mass syndrome. In this series, 16 patients had epilepsy (53 percent), 7 had haemorrhage (23.5 percent) and 7 had a mass syndrome (23.5 percent). The diagnosis of this lesion, usually obtained with angiography, has been dramatically improved by CT scan and, particularly, MRI. The natural history of cavernous angiomas is still poorly understood: the major complication is haemorrhage. Total surgical excision is the treatment of choice: it avoids a possible haemorrhage and is effective in relieving epileptic seizures. The indication for surgery depends on the clinical symptom and the location of the lesion. The post-operative morbidity in our 21 operated cases was fairly low due to minor sequelae. In only 2 of the 16 patients who had epilepsy the clinical seizures persisted after surgery, but they were less frequent. The literature is reviewed. PMID- 8367439 TI - [Acute aseptic arthritis in major sickle cell syndromes]. AB - We report 9 cases of febrile aseptic arthritis which occurred in 6 adults presenting with major sickle cell disease. The monoarticular arthritis affected the knee in 8 cases and the ankle in 1 case. Body temperature ranged from 38 degrees C to 39.5 degrees C in 7 cases, and neutrophilia (12.7 to 24 x 10(9)/l) was noted on six occasions. The always sterile synovial fluid contained 100 to 1700 cells/mm3 in 6 cases and 5200 to 12,500 cell/mm3 in 3 cases. Uricacidaemia was normal, and a search for crystals in the synovial fluid gave negative results. Bone scintigraphy and magnetic resonance imaging, performed in 3 patients, revealed the presence of a juxta-articular cortical bone infarct, whereas standard radiography was normal. In all patients, a brief immobilization and treatment with non-steroidal anti-inflammatory drugs resulted in complete cure in less than 10 days. These cases illustrate the characteristics of sickle cell arthritis, a rare complication of major sickle cell disease. Clinically, the condition resembles septic arthritis, being febrile and showing granulocytosis, but articular needle aspiration corrects the diagnosis. The mechanisms underlying these disorders have not yet been elucidated, but the bone scintigraphy and MRI performed in our patients are in favour of a reaction to a juxta-articular bone infarct. PMID- 8367440 TI - [Cardiac toxicity of anthracyclines. Clinical forms, incidence, surveillance]. AB - Anthracyclines have greatly contributed to improvement in the prognosis of certain cancers, but their beneficial effect is impaired by an unquestionable toxicity affecting notably the heart. Changes in blood pressure or electrocardiograms, benign pericardial reactions and rare but severe myocarditis may occur at an early stage of treatment. The cumulative toxicity of anthracyclines limits their use. With a cumulative dose of 550 mg/m2 the mean incidence of toxicity varies from 5 to 10 percent. The occurrence of toxicity largely depends on the total dose, but other factors such as patient's age and general condition, and previous treatments with chemo- or radiotherapy must be taken into account. The best methods to monitor the cardiotoxicity of anthracyclines are echocardiography, radionuclide study of ejection fraction and myocardial biopsy for histological study. The rational use of these three types of examination must be adjusted to each individual patient. It should reduce the incidence of severe myocarditis which sometimes cancels all the beneficial effects of the anticancer treatment. PMID- 8367441 TI - YAC transgenes: bigger is probably better. PMID- 8367442 TI - Connections between the immune system and the nervous system. PMID- 8367444 TI - In vivo transcriptional pausing and cap formation on three Drosophila heat shock genes. AB - The regulation of many eukaryotic genes occurs at the level of transcriptional elongation. On the uninduced hsp70 gene of Drosophila melanogaster, for example, an RNA polymerase II complex has initiated transcription but has paused early in elongation. In this study, we examine pausing on hsp70 and two of the small heat shock genes (hsp27 and hsp26) at high resolution, using a technique that utilizes paramagnetic particle-mediated selection of terminated run-on transcripts. This technique provides precise information on the distribution of RNA polymerase within each transcription unit. It also details the progression of 5' cap formation on the elongating transcripts. For each gene, we find polymerases paused over a relatively narrow promoter-proximal region. The regions are generally around 20 nucleotides wide, with two preferred pausing positions spaced roughly 10 nucleotides apart or about one turn of the helix. The bulk of capping occurs as transcripts pass between 20 and 30 nucleotides in length. Interestingly, in the three genes examined here, elongational pausing and 5' cap formation appear largely coincident. PMID- 8367445 TI - Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands. AB - Patients with von Willebrand disease in four families in the Aland Islands, including the original family that was described in 1926 by the Finnish physician von Willebrand, were screened for mutations in the Swedish "hot-spot" regions (exons 18, 28, 32, 43, and 45) of the von Willebrand factor gene. One cytosine deletion in exon 18 was detected in each of these families. Linkage analysis and genealogical studies suggest that the deletion present in these four families probably has an origin in common with the mutations in the Swedish patients. Apart from the deletion in exon 18, two close transitions (G-->A at S1263 and C- >T at P1266) in exon 28 on the same chromosome were identified in one individual who married into the original family and in his two children. The transitions could be due to a recombination between the von Willebrand factor gene and its pseudogene. PMID- 8367443 TI - Oxidants, antioxidants, and the degenerative diseases of aging. AB - Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great. PMID- 8367446 TI - Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. AB - The molecular mechanism responsible for the neurodegeneration in Alzheimer disease is not known; however, accumulating evidence suggests that beta-amyloid peptide (A beta P) contributes to this degeneration. We now report that synthetic A beta Ps trigger the degeneration of cultured neurons through activation of an apoptotic pathway. Neurons treated with A beta Ps exhibit morphological and biochemical characteristics of apoptosis, including membrane blebbing, compaction of nuclear chromatin, and internucleosomal DNA fragmentation. Aurintricarboxylic acid, an inhibitor of nucleases, prevents DNA fragmentation and delays cell death. Our in vitro results suggest that apoptosis may play a role in the neuronal loss associated with Alzheimer disease. PMID- 8367447 TI - Development of polyclonal antibodies against angiotensin type 2 receptors. AB - Murine neuroblastoma N1E-115 cells are a useful system in which to study neuronal angiotensin II (AngII) receptors. N1E-115 cells possess both type 1 (AT1) and type 2 (AT2) AngII receptor subtypes, as does mammalian brain. AT2 receptors in brain or N1E-115 cells can be solubilized in 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate. In the present study, heparin-Sepharose chromatography was used to partially purify solubilized N1E-115 membranes to produce an enriched population of AT2 receptors. Subsequently, an eluted peak, containing the majority of AT2 binding activity, was used as an immunogen in the development of protein-directed polyclonal antibodies. The antibodies specifically detected immunoreactive proteins of approximately 110 and 66 kDa in both solubilized N1E-115 cells, as well as the original protein material that eluted from the heparin-Sepharose column, whereas no such immunoreactivity was detected in a kidney epithelial cell line that lacks any specific 125I-labeled AngII (125I-AngII) binding activity. Moreover, the antibodies immunoreacted with affinity-purified AT2 receptors. These antibodies were also able to immunoprecipitate AT2 receptors from solubilized N1E-115 cells, as revealed by the pharmacologic profile of 125I-AngII binding to the precipitated protein. Similarly, the antibodies were able to immunoprecipitate a 66-kDa protein that had been covalently crosslinked with 125I-AngII by use of the homobifunctional crosslinker dithiobis(succinimidyl propionate). Collectively, these results demonstrate the development of a specific AT2 receptor antibody that may be used to further characterize this receptor subtype at both the cellular and molecular levels. PMID- 8367448 TI - Nerve growth factor suppresses the transforming phenotype of human prolactinomas. AB - The most effective therapy of human prolactinomas is represented by dopamine D-2 receptor agonists; there is, however, a population of nonresponder patients who require surgical intervention. In the present study, we report that prolactinomas totally resistant to pharmacological therapy have a high potential of both growing in soft agar and forming tumors in nude mice and lack D-2 receptors for dopamine. These tumors express the receptors for nerve growth factor (NGF) and are sensitive to its differentiating activity. After exposure to NGF for 4 days, prolactinoma cells decreased their proliferation rate, lost their capability to form colonies in soft agar, lost their tumorigenic activity in nude mice, and reexpressed the lactotroph-specific D-2 receptor protein inhibiting prolactin release. These effects were permanent after NGF withdrawal and were reproducible in vivo in nude mice transplanted with the tumors. NGF in fact remarkably and lastingly depressed tumor growth and induced expression of D-2 receptors when injected intravenously once a day for 5 days into prolactinoma-bearing nude mice. These data suggest that NGF may induce a long-lasting switch of gene expression in human prolactinomas, modifying their transforming phenotype and reverting them to more differentiated, less malignant, dopamine-sensitive lactotroph-like cells. The possibility thus arises that short-term treatment with NGF may restore the refractory patients to conventional pharmacological therapy with D-2 agonists. PMID- 8367449 TI - Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. AB - Activity of the mesolimbic dopaminergic system was investigated in rats withdrawn from chronic ethanol administration by single-cell extracellular recordings from dopaminergic neurons of the ventrotegmental area, coupled with antidromic identification from the nucleus accumbens, and by microdialysis-technique experiments in the nucleus accumbens. Spontaneous firing rates, spikes per burst, and absolute burst firing but not the number of spontaneously active neurons were found drastically reduced; whereas absolute and relative refractory periods increased in rats withdrawn from chronic ethanol treatment as compared with chronic saline-treated controls. Consistently, dopamine outflow in the nucleus accumbens and its acid metabolites were reduced after abruptly stopping chronic ethanol administration. All these changes, as well as ethanol-withdrawal behavioral signs, were reversed by ethanol administration. This reversal suggests that the abrupt cessation of chronic ethanol administration plays a causal role in the reduction of mesolimbic dopaminergic activity seen in the ethanol withdrawal syndrome. Results indicate that during the ethanol-withdrawal syndrome the mesolimbic dopaminergic system is tonically reduced in activity, as indexed by electrophysiological and biochemical criteria. Considering the role of the mesolimbic dopaminergic system in the reinforcing properties of ethanol, the depressed activity of this system during the ethanol-withdrawal syndrome may be relevant to the dysphoric state associated with ethanol withdrawal in humans. PMID- 8367450 TI - Reaction sequence and molecular mass of a Cl(-)-translocating P-type ATPase. AB - The basolateral membranes of Aplysia californica foregut absorptive cells contain both Cl(-)-stimulated ATPase and ATP-dependent Cl- transport activities, and each was inhibited by orthovanadate. Both of these orthovanadate-sensitive activities were reconstituted into proteoliposomes. The reaction sequence kinetics were determined by [gamma-32P]ATP-induced phosphorylation of the reconstituted Cl- pump. Rapid phosphorylation and dephosphorylation kinetics of acyl phosphate bonding were confirmed by destabilization of the phosphoprotein by either hydroxylamine or high pH. Mg2+ caused phosphorylation of the enzyme; Cl- caused dephosphorylation. Orthovanadate almost completely inhibited the Mg(2+)-driven phosphorylation reaction. The molecular mass of the catalytic unit (subunit) of the enzyme appeared to be 110 kDa, which is in agreement with molecular masses of all other catalytic units (subunits) of P-type ATPases. PMID- 8367451 TI - Energy transduction in the thermophilic anaerobic bacterium Clostridium fervidus is exclusively coupled to sodium ions. AB - The thermophilic, peptidolytic, anaerobic bacterium Clostridium fervidus is unable to generate a pH gradient in the range of 5.5-8.0, which limits growth of the organism to a narrow pH range (6.3-7.7). A significant membrane potential (delta psi approximately -60 mV) and chemical gradient of Na+ (-Z delta pNa approximately -60 mV) are formed in the presence of metabolizable substrates. Energy-dependent Na+ efflux is inhibited by the Na+/H+ ionophore monensin but is stimulated by uncouplers, suggesting that the Na+ gradient is formed by a primary pumping mechanism rather than by secondary Na+/H+ antiport. This primary sodium pump was found to be an ATPase that has been characterized in inside-out membrane vesicles and in proteoliposomes in which solubilized ATPase was reconstituted. The enzyme is stimulated by Na+, resistant to vanadate, and sensitive to nitrate, which is indicative of an F/V-type Na(+)-ATPase. In the proteoliposomes Na+ accumulation depends on the presence of ATP, is inhibited by the ATPase inhibitor nitrate, and is completely prevented by the ionophore monensin but is stimulated by protonophores and valinomycin. These and previous observations, which indicated that secondary amino acid transport uses solely Na+ as coupling ion, demonstrate that energy transduction at the membrane in C. fervidus is exclusively dependent on a Na+ cycle. PMID- 8367452 TI - RAD9-dependent G1 arrest defines a second checkpoint for damaged DNA in the cell cycle of Saccharomyces cerevisiae. AB - Exposure of the yeast Saccharomyces cerevisiae to ultraviolet (UV) light, the UV mimetic chemical 4-nitroquinoline-1-oxide (4NQO), or gamma radiation after release from G1 arrest induced by alpha factor results in delayed resumption of the cell cycle. As is the case with G2 arrest following ionizing radiation damage [Weinert, T. A. & Hartwell, L. H. (1988) Science 241, 317-322], the normal execution of DNA damage-induced G1 arrest depends on a functional yeast RAD9 gene. We suggest that the RAD9 gene product may interact with cellular components common to the G1/S and G2/M transition points in the cell cycle of this yeast. These observations define a checkpoint in the eukaryotic cell cycle that may facilitate the repair of lesions that are otherwise processed to lethal and/or mutagenic damage during DNA replication. This checkpoint apparently operates after the mating pheromone-induced G1 arrest point but prior to replicative DNA synthesis, S phase-associated maximal induction of histone H2A mRNA, and bud emergence. PMID- 8367454 TI - Secretion of a single-gene-encoded immunoglobulin from myeloma cells. AB - We describe construction of a single gene encoding a single-chain immunoglobulin like molecule. This single-gene approach circumvents inefficiencies inherent in delivering two genes into a mammalian cell and in the assembly of a functional immunoglobulin molecule. It would also facilitate ex vivo transfection of cells for gene-therapy protocols. SP2/0 murine myeloma cells transfected with the single gene SG delta CLCH1 expressed a single-chain protein, SC delta CLCH1, comprising approximately 60 kDa of the anti-carcinoma monoclonal antibody (mAb) CC49. The single-chain protein consisted of the heavy- and light-chain variable (VH and VL) domains of the mAb covalently joined through a short linker peptide, while the carboxyl end of the VL domain was linked to the amino terminus of the human gamma 1 Fc region through the hinge region. The single-chain protein assembled into a dimeric molecule, termed SCA delta CLCH1, of approximately 120 kDa and was secreted into the tissue culture fluid. SDS/PAGE analysis of the secreted immunoglobulin purified by protein G affinity chromatography confirmed the size of the molecule. The native mAb CC49 and SCA delta CLCH1 of CC49 showed similar binding to the tumor-associated glycoprotein TAG-72, and the chimeric mAb CC49 and SCA delta CLCH1 showed similar cytotoxic activity. This single-gene construct approach provides a way of generating an immunoglobulin-like molecule which retains the specificity, binding properties, and cytolytic activity of the chimeric mAb CC49. The immunoglobulin-like molecule SCA delta CLCH1 is potentially a therapeutic and diagnostic reagent against a range of human carcinomas. PMID- 8367453 TI - Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex. AB - Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is a target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. We have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. We colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC. PMID- 8367456 TI - The primary structure of a fungal chitin deacetylase reveals the function for two bacterial gene products. AB - Chitin deacetylase (EC 3.5.1.41) hydrolyzes the N-acetamido groups of N-acetyl-D glucosamine residues in chitin. A cDNA to the Mucor rouxii mRNA encoding chitin deacetylase was isolated, characterized, and sequenced. Protein sequence comparisons revealed significant similarities of the fungal chitin deacetylase to rhizobial nodB proteins and to an uncharacterized protein encoded by a Bacillus stearothermophilus open reading frame. These data suggest the functional homology of these evolutionarily distant proteins. NodB is a chitooligosaccharide deacetylase essential for the biosynthesis of the bacterial nodulation signals, termed Nod factors. The observed similarity of chitin deacetylase to the B. stearothermophilus gene product suggests that this gene encodes a polysaccharide deacetylase. PMID- 8367455 TI - Inhibition of human immunodeficiency virus type 1 replication by regulated expression of a polymeric Tat activation response RNA decoy as a strategy for gene therapy in AIDS. AB - We are investigating a strategy for somatic gene therapy to treat human immunodeficiency virus type 1 (HIV-1) infection by intracellular expression of an RNA decoy and a ribozyme. The RNA decoy, consisting of polymeric Tat activation response elements (TARs), is designed to compete for Tat binding in an equilibrium with viral TAR RNA, thereby inhibiting viral replication. The expression of polymeric TAR is regulated by the HIV long terminal repeat (LTR) and transcriptional activation is dependent on the presence of HIV Tat. Our initial studies indicated that plasmids expressing up to 50 tandem copies of TAR RNA (50TAR) inhibited tat-mediated gene expression by > 90% in a transient transfection assay. A HIV LTR-driven 50TAR construct was subcloned into a replication-defective retroviral vector to ensure high-efficiency gene transfer into T lymphocytes. In addition, a gag RNA-specific ribozyme gene was introduced into the 50TAR containing retroviral vector to enhance the inhibitory effect of the construct (designated TAR-Rib). A human T-cell line (Molt3) was infected (transduced) with the TAR-Rib recombinant retrovirus and challenged with either HIV-1 or simian immunodeficiency virus (SIV). HIV-1 replication was inhibited by 99% in the TAR-Rib-transduced T cells and was maintained over a 14-month period, suggesting that this antiviral strategy represses the formation of escape mutants. Interestingly, the TAR-Rib also inhibited SIV replication in transduced T cells, which suggests that polymeric TAR is a general inhibitor of primate lentiviruses; therefore, the macaque model could be used for further in vivo testing of this antiviral gene therapy strategy. PMID- 8367457 TI - Selective proteolytic activity of the antitumor agent kedarcidin. AB - Kedarcidin is a potent antitumor antibiotic chromoprotein, composed of an enediyne-containing chromophore embedded in a highly acidic single chain polypeptide. The chromophore was shown to cleave duplex DNA site-specifically in a single-stranded manner. Herein, we report that in vitro, the kedarcidin apoprotein, which lacks any detectable chromophore, cleaves proteins selectively. Histones that are the most opposite in net charge to the apoprotein are cleaved most readily. Our findings imply that the potency of kedarcidin results from the combination of a DNA damaging-chromophore and a protease-like apoprotein. PMID- 8367458 TI - Yeast and mammalian metallothioneins functionally substitute for yeast copper zinc superoxide dismutase. AB - Copper-zinc superoxide dismutase catalyzes the disproportionation of superoxide anion to hydrogen peroxide and dioxygen and is thought to play an important role in protecting cells from oxygen toxicity. Saccharomyces cerevisiae strains lacking copper-zinc superoxide dismutase, which is encoded by the SOD1 gene, are sensitive to oxidative stress and exhibit a variety of growth defects including hypersensitivity to dioxygen and to superoxide-generating drugs such as paraquat. We have found that in addition to these known phenotypes, SOD1-deletion strains fail to grow on agar containing the respiratory carbon source lactate. We demonstrate here that expression of the yeast or monkey metallothionein proteins in the presence of copper suppresses the lactate growth defect and some other phenotypes associated with SOD1-deletion strains, indicating that copper metallothioneins substitute for copper-zinc superoxide dismutase in vivo to protect cells from oxygen toxicity. Consistent with these results, we show that yeast metallothionein mRNA levels are dramatically elevated under conditions of oxidative stress. Furthermore, in vitro assays demonstrate that yeast metallothionein, purified or from whole-cell extracts, exhibits copper-dependent antioxidant activity. Taken together, these data suggest that both yeast and mammalian metallothioneins may play a direct role in the cellular defense against oxidative stress by functioning as antioxidants. PMID- 8367459 TI - A possible role for the yeast TATA-element-binding protein in DNA replication. AB - The TATA-element-binding protein (TBP) is involved in the initiation of transcription by all three eukaryotic RNA polymerases. The following observations implicate TBP in the initiation of DNA replication at yeast chromosomal origins as well: (i) Recombinant yeast TBP binds specifically to functionally important regions of many yeast replication origins in vitro. (ii) TBP-binding sites from RNA polymerase II promoters can activate defective replication origins in vivo. (iii) Point mutations in TBP-binding sites that diminish their affinity for TBP in vitro reduce their ability to support replication in vivo. PMID- 8367460 TI - Sodium azide mutagenesis: preferential generation of A.T-->G.C transitions in the barley Ant18 gene. AB - The molecular basis for the absence of anthocyanins and proanthocyanidins in four independent sodium azide-induced ant18 mutants of barley was examined by sequencing the gene encoding dihydroflavonol 4-reductase in these mutants. Sodium azide generated 21 base substitutions, which corresponds to 0.17% of the 12,704 nucleotides sequenced. Of the substitutions, 86% were nucleotide transitions, and 14% were transversions. A.T-->G.C base pair transitions were about 3 times more frequent than G.C-->A.T transitions. No deletions or mutation hot spots were found. The absence of dihydroflavonol 4-reductase activity in ant18-159, ant18 162, and ant18-164 plants is caused by missense mutations in the respective genes. By using microprojectile bombardment, a plasmid harboring the wild-type Ant18 gene was introduced into ant18-161 mutant cells and resulted in the development of anthocyanin pigmentation, which demonstrates that the mutation is corrected by expression of the introduced gene. On the other hand, a plasmid derivative with the two ant18-161-specific base transitions at the 5' splice site of intron 3 prevented complementation. It is concluded that the absence of detectable mRNA for dihydroflavonol 4-reductase in ant18-161 cells is due to the mutations in the pre-mRNA splice donor site. PMID- 8367461 TI - Molecular basis for the inhibition of human alpha-thrombin by the macrocyclic peptide cyclotheonamide A. AB - The macrocyclic peptide cyclotheonamide A (CtA), isolated from the marine sponge Theonella sp., represents an unusual class of serine protease inhibitor. A complex of this inhibitor with human alpha-thrombin, a protease central to the bioregulation of thrombosis and hemostasis, was studied by x-ray crystallography. This work (2.3-A resolution) confirms the structure of CtA and reveals intimate details about its molecular recognition within the enzyme active site. Interactions due to the "Pro-Arg motif" (Arg occupancy of the S1 specificity pocket; formation of a hydrogen-bonded two-strand antiparallel beta-sheet with Ser214-Gly216) and the alpha-keto amide group of CtA are primarily responsible for binding to thrombin, with the alpha-keto amide serving as a transition-state analogue. A special interaction with the "insertion loop" of thrombin (Tyr60A Thr60I) is manifested through engagement of the hydroxyphenyl group of CtA with Trp60D as part of an "aromatic stacking chain." Biochemical inhibition data (Ki values at 37 degrees C) were obtained for CtA with thrombin and a diverse collection of serine proteases. Thus, CtA is just a moderate inhibitor of human alpha-thrombin (Ki = 0.18 microM) but a potent inhibitor of trypsin (Ki = 0.023 microM) and streptokinase (Ki = 0.035 microM). The relative lack of potency of CtA as a thrombin inhibitor is discussed with respect to certain structural features of the enzyme complex. We also report the total synthesis of CtA, by a convergent [2 + 3] fragment-condensation approach, to serve the preparation of cyclotheonamide analogues for structure-function studies. PMID- 8367462 TI - Comparison of the P2 specificity pocket in three human histocompatibility antigens: HLA-A*6801, HLA-A*0201, and HLA-B*2705. AB - Coordinates from x-ray structures of HLA-A*6801, HLA-A*0201, and HLA-B*2705 were analyzed to examine the basis for their selectivity in peptide binding. The pocket that binds the side chain of the peptide's second amino acid residue (P2 residue) shows a preference for Val, Leu, and Arg in these three HLA subtypes, respectively. The Arg-specific pocket of HLA-B*2705 differs markedly from those of HLA-A*0201 and HLA-A*6801, as a result of numerous differences in the side chains that form the pocket's surface. The cause of the specificity differences between HLA-A*0201 and HLA-A*6801 is more subtle and depends both on a change in conformation of pocket residue Val-67 and on a sequence difference at residue 9. The Val-67 conformational change appears to be caused by a shift in the position of the alpha 1-domain alpha-helix relative to the beta-sheet in the cleft and may, in fact, depend on amino acid differences remote from the P2 pocket. Analysis of the stereochemistry of the P2 side chain interacting with its binding pocket permits an estimate to be made of its contribution to the free-energy change of peptide binding. PMID- 8367463 TI - Isoproterenol stimulates rapid extrusion of sodium from isolated smooth muscle cells. AB - beta-Agonists cause an inhibition of contractility and a transient stimulation of Na+/K+ pumping in smooth muscle cells of the stomach from the toad Bufo marinus. To determine if the stimulation of Na+/K+ pumping causes changes in intracellular [Na+] ([Na+]i) that might link Na+ pump stimulation to decrease Ca2+ availability for contraction, [Na+]i was measured in these cells with SBFI, a Na(+)-sensitive fluorescent indicator. Basal [Na+]i was 12.8 +/- 4.2 mM (n = 32) and was uniform throughout the cell. In response to isoproterenol, [Na+]i decreased an average of 7.1 +/- 1.1 mM in 3 sec. Since this decrease in [Na+]i could be completely blocked by inhibition of the Na+ pump, or by blockade of the beta-receptor, [Na+]i reduction is the result of occupation of the beta-receptor by isoproterenol and subsequent stimulation of the Na+ pump. 8-Bromoadenosine 3',5' cyclic monophosphate and forskolin mimicked the effect of isoproterenol, indicating that the sequence of events linking beta-receptor occupation to Na+ pump stimulation most likely includes activation of adenylate cyclase, production of cAMP, and stimulation of cAMP-dependent protein kinase. The decrease in [Na+]i is sufficiently large and fast that it is expected to stimulate turnover of the Na+/Ca2+ exchanger in the Ca2+ extrusion mode, thereby accounting for the observed linkage between stimulation of the Na+/K+ pump and inhibition of contractility in response to beta-adrenergic agonists. PMID- 8367464 TI - The E2A gene product contains two separable and functionally distinct transcription activation domains. AB - The E2A gene encodes transcription factors of the helix-loop-helix (HLH) family which are implicated in cell-specific transcriptional control in several cell lineages, including pancreatic beta cells. In the present work, we show by deletion mapping of both the E2A protein itself and the Gal4-E2A fusion protein that the protein contains at least two distinct activation domains. One domain (located between amino acids 1 and 153) functions efficiently in a variety of mammalian cell lines. The second domain (located between amino acids 369 and 485) functions preferentially in pancreatic beta cell lines. The latter domain shows a pattern of heptad repeats of leucine residues characteristics of "leucine zipper" transcription factors; site-directed mutagenesis of leucines within this repeat led to substantial reductions in activity. The selective properties of this activation domain may contribute to cell-specific transcription directed by the E2A gene. PMID- 8367465 TI - Control analysis of the dependence of Escherichia coli physiology on the H(+) ATPase. AB - The H(+)-ATPase plays a central role in Escherichia coli free-energy transduction and hence in E. coli physiology. We here investigate the extent to which this enzyme also controls the growth rate, growth yield, and respiratory rate of E. coli. We modulate the expression of the atp operon and determine the effect on said properties. When quantified in terms of control coefficients, we find that, in the wild-type cell growing on glucose in minimal medium, this key enzyme (H(+) ATPase) exerts virtually no control on growth rate (magnitude of C < 0.01), a minor positive control on growth yield (C = 0.15), and a small but negative control on respiration rate (C = -0.25). The control the enzyme exerts on the consumption rate of the carbon and free-energy substrate is negative (C = -0.15). We also studied how the control coefficients themselves vary with the expression of the atp operon. As the level of expression of the atp operon was reduced, the control exerted by the H(+)-ATPase on growth rate and growth yield increased slightly; the control on growth rate passed through a maximum (C = 0.1) and disappeared when the atp operon was not expressed at all, reflecting that with this substrate there are alternative routes for ATP synthesis. At elevated levels of the H(+)-ATPase compared to the wild type, the control exerted by the enzyme on growth rate became negative. The evolutionary context of the absence of control by the atp operon on growth rate is discussed. PMID- 8367466 TI - Transactivation by hepatitis B virus X protein is promiscuous and dependent on mitogen-activated cellular serine/threonine kinases. AB - The X protein of hepatitis B virus (HBV-X) can act as a transactivator of transcription but its mechanism of action remains obscure. We have analyzed HBV-X transactivation in several cell types using 13 unrelated viral and cellular promoters and found that transactivation is more or less apparent in most cell types and is promiscuous and unrelated to specific sequence motifs within the target promoters. In general, though, HBV-X appears to act on enhancer elements since HBV-X had no effect on a minimal promoter, whereas HBV-X was able to transactivate after insertion of an AP-1 minienhancer. Several lines of evidence exclude the possibility that HBV-X interacts directly with the AP-1 enhancer or its binding proteins and suggest that the proximal target of HBV-X is peripheral to the transcription complex. This hypothesis is supported by the observation that inhibition of serine/threonine kinases, which regulate AP-1 activity (phorbol ester down-regulation or staurosporine inhibition of protein kinase C and a dominant negative mutant of Raf-1), blocked the ability of HBV-X to transactivate without affecting basal promoter activity. Furthermore, basal transcription from the AP-1-dependent promoter was increased by overexpression of protein kinase C and Raf-1 but HBV-X was unable to further stimulate, indicating that these kinases act subsequently to HBV-X. These data suggest that transactivation by HBV-X is an indirect result of the activation of cellular serine/threonine kinases including protein kinase C and Raf-1. This mode of action implies that HBV-X may affect other cellular processes, besides transcription, that are regulated by these kinases. PMID- 8367467 TI - Transfer of genetic information in the rp49 region of Drosophila subobscura between different chromosomal gene arrangements. AB - Nucleotide variation in the region including the ribosomal protein 49 (rp49) gene was investigated by direct sequencing of 10 alleles of Drosophila subobscura from chromosomes differing in gene arrangements. Fifty-six nucleotide and seven length polymorphisms were detected over a 1.5-kb region. Of the 20 nucleotide polymorphisms present more than once in the sample, 13 were segregating in O[3 + 4], 9 in O[3 + 4 + 8], and 4 in O[st] chromosomal classes. Several of these polymorphisms were segregating in more than one chromosomal class, a strong indication of genetic transfer between different chromosomal gene arrangements either by double crossover or gene conversion. Given the probable role played by gene conversion in the history of the rp49 region in D. subobscura, estimates of nucleotide diversity within chromosomal class indicate that the O[3 + 4] chromosomal gene arrangement is older than the O[st] arrangement. PMID- 8367468 TI - Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse. AB - We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II. PMID- 8367469 TI - Probing the function of Drosophila melanogaster accessory glands by directed cell ablation. AB - The female Drosophila melanogaster fly undergoes behavioral changes after mating, including an increase in egg laying and an avoidance of remating. Accessory-gland products elicit these changes transiently when introduced into unmated female flies. We report here the generation and phenotype of flies that lack functional accessory-gland main cells as a consequence of genetically directed delivery of diphtheria toxin subunit A to those cells. Only main-cell secretions are essential for the short-term inhibition to remating; no other products of the genital tract can replace their function. Long-term inhibition to remating depends only on the storage of sperm in the female. Both sperm and main-cell secretions have roles in the increase of egg laying by the mated female. In addition to full-strength diphtheria toxin, we used low-activity toxins to kill only those cells that express toxin at high levels. These transgenic strains that express diphtheria toxins of different strengths in accessory-gland main cells will be useful in further defining the role of these cells. PMID- 8367470 TI - Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform specific effects and implications for late-onset Alzheimer disease. AB - Apolipoprotein E (apoE), a plasma apolipoprotein that plays a central role in lipoprotein metabolism, is localized in the senile plaques, congophilic angiopathy, and neurofibrillary tangles of Alzheimer disease. Late-onset familial and sporadic Alzheimer disease patients have an increased frequency of one of the three common apoE alleles, epsilon 4, suggesting apoE4 is associated with increased susceptibility to disease. To follow up on this suggestion, we compared the binding of synthetic amyloid beta (beta/A4) peptide to purified apoE4 and apoE3, the most common isoform. Both isoforms bound synthetic beta/A4 peptide, the primary constituent of the plaque and angiopathy, forming a complex that resisted dissociation by boiling in SDS. Oxygen-mediated complex formation was implicated because binding was increased in oxygenated buffer, reduced in nitrogen-purged buffer, and prevented by reduction with dithiothreitol or 2 mercaptoethanol. Binding of beta/A4 peptide was saturable at 10(-4) M peptide and required residues 12-28. Examination of apoE fragments revealed that residues 244 272 are critical for complex formation. Both oxidized apoE4 and apoE3 bound beta/A4 peptide; however, binding to apoE4 was observed in minutes, whereas binding to apoE3 required hours. In addition, apoE4 did not bind beta/A4 peptide at pH < 6.6, whereas apoE3 bound beta/A4 peptide from pH 7.6 to 4.6. Together these results indicate differences in the two isoforms in complexing with the beta/A4 peptide. Binding of beta/A4 peptide by oxidized apoE may determine the sequestration or targeting of either apoE or beta/A4 peptide, and isoform specific differences in apoE binding or oxidation may be involved in the pathogenesis of the intra- and extracellular lesions of Alzheimer disease. PMID- 8367471 TI - Production of unmodified human adult hemoglobin in Escherichia coli. AB - We have constructed a plasmid (pHE2) in which the synthetic human alpha- and beta globin genes and the methionine aminopeptidase (Met-AP) gene from Escherichia coli are coexpressed under the control of separate tac promoters. The Hbs were expressed in E. coli JM109 and purified by fast protein liquid chromatography, producing two major components, a and b. Electrospray mass spectrometry shows that at least 98% and about 90% of the expressed alpha and beta chains of component a, respectively, have the expected masses. The remaining 10% of the beta chain in component a corresponds in mass to the beta chain plus methionine. In component b, both alpha and beta chains have the correct masses without detectable N-terminal methionine (< 2%). These results have been confirmed by Edman degradation studies of the amino-terminal sequences of the alpha and beta chains of these two recombinant Hb (rHb) samples. rHbs from components a and b exhibit visible optical spectra identical to that of human normal adult Hb (Hb A). Component a and Hb A have very similar oxygen-binding properties, but component b shows somewhat altered oxygen binding, especially at low pH values. 1H-NMR spectra of component a and Hb A are essentially identical, whereas those of component b exhibit altered ring current-shifted and hyperfine-shifted proton resonances, indicating altered heme conformation in the beta chain. These altered resonance patterns can be changed to those of Hb A by converting component b to the ferric state and then to the deoxy state and finally back to either the carbonmonoxy or oxy form. Thus, our E. coli expression system produces native, unmodified Hb A in high yield and can be used to produce desired mutant Hbs. PMID- 8367472 TI - Recombination walking: genetic selection of clones from pooled libraries of yeast artificial chromosomes by homologous recombination. AB - Recombination walking is based on the genetic selection of specific human clones from a yeast artificial chromosome (YAC) library by homologous recombination. The desired clone is selected from a pooled (unordered) YAC library, eliminating labor-intensive steps typically used in organizing and maintaining ordered YAC libraries. Recombination walking represents an efficient approach to library screening and is well suited for chromosome-walking approaches to the isolation of genes associated with common diseases. PMID- 8367473 TI - Radish, a Drosophila mutant deficient in consolidated memory. AB - We have characterized the behavior and genetics of the Drosophila mutant radish (rsh gene). Initial learning of radish flies in two olfactory discrimination tests is high, but subsequent memory decays rapidly at both early and late times after training. Anesthesia-resistant memory (consolidated memory) is undetectable in radish flies 3 hr after training. The mutant shows normal locomotor activity and normal sensitivity to the odor cues and electric-shock reinforcement used in the learning tests. The radish gene maps within a 180-kb interval in the 11D-E region of the X chromosome. PMID- 8367474 TI - Response variability in retinal ganglion cells of primates. AB - The signal encoded by a sensory neuron is usually characterized as the cell's average response to repeated presentations of a stimulus. However, each stimulus presentation elicits a slightly different response. This response variability may obscure the signal represented by neural activity, but it might also be an important aspect of a neuron's message and in some instances may even serve useful function. Here we present evidence that response variability (noise) in primate retinal ganglion cells at photopic light levels is (i) independent of the amplitude of either the stimulus or the response and is therefore additive, (ii) independent of receptive field size and retinal eccentricity, and (iii) similar for all primate ganglion cells. Our results show that the primate retina maintains a uniform noise level across the entire visual field and suggest that the noise originates within the ganglion cells themselves. PMID- 8367476 TI - Major histocompatibility complex monomorphism and low levels of DNA fingerprinting variability in a reintroduced and rapidly expanding population of beavers. AB - Loss of genetic variation due to population bottlenecks may be a severe threat for the survival of endangered species. Assessment and maintenance of genetic variability are thus crucial for conservation programs related to endangered populations. Scandinavian beavers went through an extensive bottleneck during the last century due to overhunting. In Sweden the species became extirpated but in Norway extinction was avoided by legal protection. Following reintroductions of small numbers of remaining Norwegian animals in 1922-1939, the Swedish population has increased tremendously, now harboring 100,000 animals. We show here that this viable population of beavers possesses extremely low levels of genetic variability at DNA fingerprinting loci and monomorphism at major histocompatibility complex (MHC) class I and class II loci. A similar pattern was also evident among Norwegian beavers but low levels of genetic variability were not a characteristic of the species since Russian conspecifics displayed substantial DNA fingerprinting polymorphism. However, the Russian animals were monomorphic at MHC loci, indicating that the European beaver is exceptional in its low level of MHC variability. The results demonstrate that a conservation program can be successful despite low levels of genetic variation in the founder population. PMID- 8367475 TI - A transcription inhibitor specific for unwound DNA in RNA polymerase-promoter open complexes. AB - The kinetically component open complexes formed at prokaryotic and eukaryotic transcription start sites are efficiently nicked by the chemical nuclease activity of the 2:1 1,10-phenanthroline-copper(I) complex [(OP)2Cu+] and hydrogen peroxide. This reaction specificity has been attributed to the creation of a binding site(s) for redox-active tetrahedral (OP)2Cu+ when RNA polymerase form productive complexes with promoters. This proposal has been confirmed for the Escherichia coli lac UV-5 promoter by the demonstration that the 2:1 2,9-dimethyl 1,10-phenanthroline-copper(I) complex [(Me2OP)2Cu+], a redox-inactive isostere of (OP)2-Cu+, protects the transcription start site from scission by the chemical nuclease activity. (Me2OP)2Cu+ is also an effective inhibitor of transcription. The inhibition of transcription and the protection from scission of the open complex by (OP)2Cu+ exhibit the same dependence on the concentration of (Me2OP)2Cu+. This redox- and exchange-stable species is a previously undescribed transcription inhibitor that binds to a site generated by the interaction of RNA polymerase with the promoter. Unlike the intercalating agent proflavine, which is also an effective transcription inhibitor, it does not displace the enzyme from the promoter. The ability of (Me2OP)2Cu+ to inhibit transcription may be partially responsible for its potent cytotoxicity. PMID- 8367477 TI - Glyceraldehyde-3-phosphate dehydrogenase on the surface of group A streptococci is also an ADP-ribosylating enzyme. AB - We recently identified an enzymatically active glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12; GAPDH) as a major protein on the surface of group A streptococci (SDH), which exhibits multiple binding activity to various mammalian proteins. We now report that the SDH molecule also functions as an ADP ribosylating enzyme, which, in the presence of NAD, is auto-ADP-ribosylated. In a crude cell wall extract of group A streptococci, SDH is the only protein that is ADP-ribosylated. SDH found in the streptococcal cytoplasmic fraction could not be ADP-ribosylated in the presence of NAD. Treatment of ADP-ribosylated SDH with the cytoplasmic fraction removed the ADP-ribose from SDH, suggesting the presence of an ADP-ribosyl hydrolase in the cytoplasmic compartment. The covalent linkage of ADP-ribose to SDH was stable to neutral hydroxylamine, sensitive to HgCl2, and inhibitable by free cysteine, indicating that the modification was at a cysteine residue of SDH. In addition to its auto-ADP-ribosylation activity, purified SDH or streptococcal cell wall extracts were able to transfer the ADP-ribose moiety of NAD specifically to free cysteine, resulting in a true thioglycosidic linkage. Treatment of purified SDH or the crude cell wall extract with sodium nitroprusside, which spontaneously generates nitric oxide, was found to stimulate the ADP-ribosylation of SDH in a time-dependent manner. ADP-ribosylation and nitric oxide treatment inhibited the GAPDH activity of SDH. Since ADP ribosylation and nitric oxide are involved in signal transduction events, the ADP ribosylating activity of SDH may enable communication between host and parasite during infection by group A streptococci. PMID- 8367478 TI - PMT1, the gene for a key enzyme of protein O-glycosylation in Saccharomyces cerevisiae. AB - The integral endoplasmic reticulum membrane protein catalyzing the initial reaction of protein O-glycosylation in Saccharomyces cerevisiae has been purified to homogeneity. The 92-kDa N-glycosylated protein transfers mannose residues from dolichyl phosphate-D-mannose to specific serine/threonine residues of proteins entering the secretory pathway. This type of mannosyl transfer reaction has so far been observed only in fungal cells. Oligonucleotides derived from peptide sequences of the transferase were used to screen a genomic yeast library. A clone was isolated which contains an open reading frame of 2451 bp corresponding to an mRNA transcript of 3 kb. The predicted protein consists of 817 amino acids including three potential N-glycosylation sites. The hydropathy plot indicates a tripartite structure of the protein: an amino-terminal third and a carboxyl terminal third, both with multiple potential transmembrane helices, and a central hydrophilic part. Expression of the clone in Escherichia coli resulted in mannosyltransferase activity. Gene disruption led to a complete loss of in vitro mannosyltransferase activity from dolichyl phosphate-D-mannose to a peptide used as acceptor in the enzymatic assay. In vivo it was observed, however, that protein O-mannosylation in the disruptant had decreased only to about 40-50%, indicating the existence of an additional transferase which had not been measured by the in vitro enzyme assay. PMID- 8367479 TI - Targeting of the UmuD, UmuD', and MucA' mutagenesis proteins to DNA by RecA protein. AB - In addition to its critical role in genetic recombination, the Escherichia coli RecA protein plays a pivotal role in SOS-induced mutagenesis. This role can be separated genetically into three steps: (i) depression of the SOS regulon by mediating the posttranslational cleavage of the LexA repressor, (ii) activation of UmuD'-like proteins by mediating cleavage of the UmuD-like proteins, and (iii) a direct step, possibly to interact with and to target the Umu-like mutagenesis proteins to lesions in DNA. We have analyzed RecA's third role biochemically using protein affinity chromatography and an agarose-based DNA mobility-shift assay. RecA730 protein from a crude cell extract was specifically retained on UmuD and UmuD' protein affinity columns, suggesting that these proteins physically interact. Normally, neither UmuD nor UmuD' shows any affinity for DNA. In the presence of RecA protein, however, UmuD and UmuD' were targeted to DNA. RecA1730 protein, which is defective for UmuD' but proficient for MucA'-promoted mutagenesis, showed a dramatically reduced capacity to target UmuD' to DNA but was able to target a significant portion of MucA' to DNA. These data support the suggestion that the direct role of RecA protein in SOS-induced mutagenesis is to interact with and target the Umu-like mutagenesis proteins to DNA. PMID- 8367480 TI - Crystal structure of yeast TATA-binding protein and model for interaction with DNA. AB - The C-terminal 179-aa region of yeast (Saccharomyces cerevisiae) TATA-binding protein (TBP), phylogenetically conserved and sufficient for many functions, formed crystals diffracting to 1.7-A resolution. The structure of the protein, determined by molecular replacement with coordinates from Arabidopsis TBP and refined to 2.6 A, differed from that in Arabidopsis slightly by an angle of about 12 degrees between two structurally nearly identical subdomains, indicative of a degree of conformational flexibility. A model for TBP-DNA interaction is proposed with the following important features: the long dimension of the protein follows the trajectory of the minor groove; two rows of basic residues conserved between the subdomains lie along the edges of the protein in proximity to the DNA phosphates; a band of hydrophobic residues runs down the middle of the groove; and amino acid residues whose mutation alters specificity for the second base of the TATA sequence are juxtaposed to that base. PMID- 8367481 TI - Identification of a gene required for membrane protein retention in the early secretory pathway. AB - The yeast SEC12 gene product (Sec12p) is an integral membrane protein required for the protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus. Although this protein is almost exclusively localized in the ER, a significant fraction of Sec12p is modified by an enzyme that resides in the early compartment of the Golgi apparatus, suggesting that Sec12p is cycling between the ER and the early Golgi. We have taken a genetic approach to investigate the retention mechanism of Sec12p. Analysis of mutants that are defective in the retention of the Sec12-Mf alpha 1 fusion protein in the early secretory compartments has identified a gene, RER1. A recessive mutation in RER1 causes mislocalization of the authentic Sec12p as well as two different Sec12 fusion proteins to the late Golgi apparatus and even to the cell surface. However, the rer1 mutant is not defective in the retention of an ER-resident soluble protein, BiP, suggesting that soluble and membrane proteins are retained in the ER by distinct mechanisms. PMID- 8367482 TI - Hypersensitivity to diphtheria toxin by mouse cells expressing both diphtheria toxin receptor and CD9 antigen. AB - DTS-II is a highly diphtheria toxin (DT)-sensitive cell line previously isolated by transfection of wild-type DT-resistant mouse L-M(TK-) cells with the cDNA encoding a monkey Vero cell DT receptor. DTS-II cells are as toxin-sensitive as Vero cells, have approximately 3-fold more receptors than Vero cells, and have approximately 10-fold lower affinity for DT than Vero cells. We now cotransfected DTS-II cells with a plasmid containing the Vero cell cDNA coding for CD9 antigen (pCD9) and with a plasmid containing the gene for hygromycin resistance (pHyg). The stably transfected hygromycin-resistant colonies were screened for DT hypersensitivity employing a replica plate system. A DT-hypersensitive colony was isolated and purified. The purified DT-hypersensitive cells, DTS-III, (i) are approximately 10-fold more toxin-sensitive than DTS-II and Vero cells and (ii) bear approximately 10(6) DT receptors per cell (i.e., approximately 20-fold and approximately 60-fold more receptors than DTS-II and Vero cells, respectively), but their receptor affinity is still approximately 10-fold lower than that of Vero cells. Cross-linking experiments employing 125I-labeled DT demonstrated that DTS-II and DTS-III cells have essentially the same profile of DT-binding cell surface protein(s), suggesting that CD9 antigen, although expressed on the cell surface of DTS-III cells, may not be in close proximity to the DT-binding domain of the receptor. CD9 may affect DT receptor expression by increasing receptor density at the cell surface. By employing DTS-III cells it should be possible to purify and characterize the DT cell-surface receptor protein(s). PMID- 8367483 TI - Cytotoxic and interferon gamma-producing activities of gamma delta T cells in the mouse intestinal epithelium are strain dependent. AB - We have analyzed the cytolytic activity of freshly isolated intraepithelial T cells (i-IEL) from the intestines of several different mouse strains in an anti-T cell receptor monoclonal antibody-mediated redirected lysis assay. The cytolytic activity of gamma delta i-IEL but not that of alpha beta i-IEL was strain dependent. Mouse strains could be divided into high (H), marginal (M), and null (N) strains. The anti-gamma delta T-cell receptor monoclonal antibody-induced interferon gamma production showed the same strain-dependent variability, but the proliferative responses to gamma delta T-cell receptor crosslinking did not show this variability. The N phenotype of gamma delta i-IEL was found to be dominant in (H x N)F1 mice. In radiation bone-marrow chimeras the H/N phenotype was determined by the genotype of the reconstituting bone-marrow-derived cells but was not determined by the genotype of the radioresistant host cells. Analysis of (H x N)F1 backcross animals indicated that at least two genes are involved in determination of the H/N phenotype. One of these genes is major histocompatibility-complex linked. No difference in the use of the variable region segment of the gamma-chain or delta-chain was seen between the gamma delta i-IEL from H and N strains. Various models that might explain the strain dependent gamma delta i-IEL phenotypes are discussed. PMID- 8367484 TI - Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease. AB - Since memory loss is characteristic of Alzheimer disease (AD), and since K+ channels change during acquisition of memory in both molluscs and mammals, we investigated K+ channel function as a possible site of AD pathology and, therefore, as a possible diagnostic index as well. A 113-pS tetraethylammonium (TEA)-sensitive K+ channel was consistently absent from AD fibroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invariable absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2+ signal indicate K+ channel dysfunction in AD fibroblasts. These results suggest the possibility of a laboratory method that would diagnostically distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD neurological and psychiatric disorders. PMID- 8367486 TI - CCAAT/enhancer-binding protein mRNA is translated into multiple proteins with different transcription activation potentials. AB - The CCAAT/enhancer-binding protein (C/EBP) alpha is a leucine zipper protein that is preferentially expressed in certain cell types, such as adipocytes and hepatocytes. Here we show that C/EBP alpha mRNA is translated into two major proteins, C/EBP-42 and C/EBP-30, that differ in their content of N-terminal amino acid sequences. These results are best explained by a ribosome-scanning mechanism in which a fraction of ribosomes ignore the first two AUGs and initiate translation at an AUG located 351 nt downstream of the first one. Because C/EBP 30, the translation product initiated at the third AUG, is devoid of the potent transcription-activation domain contained in C/EBP-42, the former protein stimulates transcription from the mouse albumin promoter much less efficiently than the latter. The gene encoding the liver-enriched transcriptional-activator protein LAP (C/EBP-beta) has also been shown to issue two proteins, LAP and the liver-enriched transcriptional-inhibitory protein LIP, with different transcription-activation potentials. The production of multiple proteins from a single mRNA is not only shared between different C/EBP family members but also appears to be conserved in vertebrate evolution. PMID- 8367485 TI - In vivo clonal dominance and limited T-cell receptor usage in human CD4+ T-cell recognition of house dust mite allergens. AB - Sensitivity to house dust mite antigens in atopic individuals is a major cause of allergic diseases, ranging from asthma to rhinitis and dermatitis. We have studied the T-cell receptor (TCR) usage of house-dust-mite-specific CD4+ T-cell clones isolated from an atopic individual, by using the anchored polymerase chain reaction, and have analyzed the peripheral TCR repertoire of the same individual. Several T-cell clones had identified TCRs at the sequence level, despite the fact that they had been independently isolated, in some cases, in different years. These data suggest the presence in vivo of long-lived T-cell clones. We have also shown that junctional sequences identical to these clones are present in peripheral blood T cells taken 6 years after the isolation of the T-cell clones. The analysis of TCR genes used by the panel of clones reveals oligoclonality, with the variable (V) region gene segments V alpha 8 and V beta 3 being dominant, although there is minimal conservation of junctional sequences. The results have implications for understanding the TCR recognition of an environmental aeroallergen and the life span of T-cell clones in vivo during a chronic immune response. PMID- 8367487 TI - Evidence that the 60-kDa protein of 17S U2 small nuclear ribonucleoprotein is immunologically and functionally related to the yeast PRP9 splicing factor and is required for the efficient formation of prespliceosomes. AB - Small nuclear ribonucleoprotein (snRNP) U2 functions in the splicing of mRNA by recognizing the branch site of unspliced mRNA. The binding of U2 snRNP and other components to pre-mRNA leads to the formation of a stable prespliceosome. In HeLa nuclear extracts, U2 snRNP exists either as a 17S form (under low salt conditions) or a 12S form (at higher salt concentrations). We have recently shown that the purified 17S U2 snRNP contains nine proteins with apparent molecular masses of 35, 53, 60, 66, 92, 110, 120, 150, and 160 kDa in addition to the common snRNP proteins and the U2 proteins A' and B" that are found in the 12S U2 snRNP form. By using antibodies against the PRP9 protein from Saccharomyces cerevisiae (a protein required for the addition of U2 to prespliceosomes in yeast), we have shown that the 60-kDa protein specific to human U2 snRNP particles is structurally related to the yeast PRP9 protein. Interestingly, anti PRP9 antibodies strongly inhibit prespliceosome formation in HeLa nuclear splicing extracts, resulting in a complete inhibition of the mRNA splicing reaction in vitro. This indicates that the U2 60-kDa protein may also be functionally related to its yeast counterpart PRP9. Most importantly, the addition of purified 17S U2 snRNPs, but not of 12S U2 snRNPs, to HeLa splicing extracts in which the endogeneous U2 snRNPs have been functionally neutralized with anti-PRP9 antibodies fully restores the mRNA-splicing activity of the extracts. These data suggest further that the 17S form is the functionally active form of U2 snRNP in the spliceosome. PMID- 8367488 TI - Abundant mitochondrial DNA variation and world-wide population structure in humpback whales. AB - Hunting during the last 200 years reduced many populations of mysticete whales to near extinction. To evaluate potential genetic bottlenecks in these exploited populations, we examined mitochondrial DNA control region sequences from 90 individual humpback whales (Megaptera novaeangliae) representing six subpopulations in three ocean basins. Comparisons of relative nucleotide and nucleotype diversity reveal an abundance of genetic variation in all but one of the oceanic subpopulations. Phylogenetic reconstruction of nucleotypes and analysis of maternal gene flow show that current genetic variation is not due to postexploitation migration between oceans but is a relic of past population variability. Calibration of the rate of control region evolution across three families of whales suggests that existing humpback whale lineages are of ancient origin. Preservation of preexploitation variation in humpback whales may be attributed to their long life-span and overlapping generations and to an effective, though perhaps not timely, international prohibition against hunting. PMID- 8367489 TI - An upstream open reading frame represses expression of Lc, a member of the R/B family of maize transcriptional activators. AB - The R/B genes of maize encode a family of basic helix-loop-helix proteins that determine where and when the anthocyanin-pigment pathway will be expressed in the plant. Previous studies showed that allelic diversity among family members reflects differences in gene expression, specifically in transcription initiation. We present evidence that the R gene Lc is under translational control. We demonstrate that the 235-nt transcript leader of Lc represses expression 25- to 30-fold in an in vivo assay. Repression is mediated by the presence in cis of a 38-codon upstream open reading frame. Furthermore, the coding capacity of the upstream open reading frame influences the magnitude of repression. It is proposed that translational control does not contribute to tissue specificity but prevents overexpression of the Lc protein. The diversity of promoter and 5' untranslated leader sequences among the R/B genes provides an opportunity to study the coevolution of transcriptional and translational mechanisms of gene regulation. PMID- 8367490 TI - Day/night and circadian rhythm control of con gene expression in Neurospora. AB - In the filamentous fungus Neurospora crassa, several events in the process of conidiation are influenced by light. Two genes, con-6 and con-10, which were previously shown to be transcriptionally activated during conidiation and by exposure to light, were found to be unexpressed in mycelium maintained in constant darkness or in constant light. However, when mycelium was shifted from darkness to light, transcripts of both genes appeared and were abundant. Upon further illumination both transcripts disappeared--i.e., their continued production was light repressed. When dark-grown mycelium was exposed to a light pulse and reincubated in the dark, expression of con-6 and con-10 exhibited a 20 hr circadian periodicity. Both genes were photoinducible throughout the stages of the circadian cycle. In the mutant strains bd and bd;frq9, con-6 and con-10 were light inducible but were not normally light repressible. Mutant genes such as acon-2, acon-3, and fl that block developmental expression of con-6 and/or con-10 did not prevent their photoinduction. PMID- 8367491 TI - Delineation of an extended surface contact area on human CD4 involved in class II major histocompatibility complex binding. AB - We describe a detailed mapping of the class II major histocompatibility complex (MHC) binding site using site-directed mutagenesis in conjunction with high resolution CD4 structural data. Residues on all lateral surfaces of domain 1 and the neighboring portions of domain 2 participate in contacting class II MHC. Thus, in addition to the C'C" ridge that forms the human immunodeficiency virus type 1 gp120 binding site, apparent MHC contacts extend over the BED face of domain 1 and across the interdomain groove onto the FG loop of domain 2. Several models of the CD4/class II MHC interaction accounting for the extent of the CD4 surface involved are discussed, including the possibility that CD4 may contact more than one class II MHC molecule using different surfaces. PMID- 8367493 TI - A correlational model for the development of disparity selectivity in visual cortex that depends on prenatal and postnatal phases. AB - Neurons in the visual cortex require correlated binocular activity during a critical period early in life to develop normal response properties. We present a model for how the disparity selectivity of cortical neurons might arise during development. The model is based on Hebbian mechanisms for plasticity at synapses between geniculocortical neurons and cortical cells. The model is driven by correlated activity in retinal ganglion cells within each eye before birth and additionally between eyes after birth. With no correlations present between the eyes, the cortical model developed only monocular cells. Adding a small amount of correlation between eyes at the beginning of development produced cortical neurons that were entirely binocular and tuned to zero disparity. However, if an initial phase of purely same-eye correlations was followed by a second phase of development that included correlations between eyes, the cortical model became populated with both monocular and binocular cells. Moreover, in the two-phase model, binocular cells tended to be selective for zero disparity, whereas the more monocular cells tended to have nonzero disparity. This relationship between ocular dominance and disparity has been observed in the visual cortex of the cat by other workers. Differences in the relative timing of the two developmental phases could account for the higher proportion of monocular cells found in the visual cortices of other animals. PMID- 8367492 TI - Ectopic neural expression of a floor plate marker in frog embryos injected with the midline transcription factor Pintallavis. AB - The floor plate, a cell group that develops at the midline of the neural plate in response to inductive signals from the notochord, has been implicated in the control of dorsoventral neural pattern. The frog Pintallavis gene, encoding a member of the HNF-3/fork head transcription factor family, is expressed in the notochord and in midline neural plate cells that give rise to the floor plate. To examine whether Pintallavis might be involved in regulating the differentiation of the floor plate, we ectopically expressed Pintallavis by injection of synthetic mRNA into two-cell frog embryos. Injection of Pintallavis mRNA resulted in the ectopic expression of F-spondin, a gene encoding a floor plate-specific adhesion molecule, at the dorsal midline of the neural tube. The expression of Pintallavis in midline cells may therefore contribute to the establishment of the floor plate fate. PMID- 8367494 TI - Design of peptide enzymes (pepzymes): surface-simulation synthetic peptides that mimic the chymotrypsin and trypsin active sites exhibit the activity and specificity of the respective enzyme. AB - Two 29-residue peptides were prepared, one of which (ChPepz) was designed by surface-simulation synthesis to mimic the active site of alpha-chymotrypsin, and the other (TrPepz), which contained four substitutions relative to ChPepz, was fashioned after the active site of trypsin. Each peptide was cyclized by a disulfide bond. The ChPepz monomer effected hydrolysis of the ester group in N benzoyl-L-tyrosine ethyl ester, an alpha-chymotrypsin substrate, with Km and kcat values that were comparable to those of alpha-chymotrypsin. ChPepz was completely inactivated by diisopropyl fluorophosphate (DIFP), L-1-p-tosylamino-2-phenylethyl chloromethyl ketone (TPCK), or reduction of the disulfide bond. It had no catalytic activity on N-tosyl-L-arginine methyl ester, a trypsin substrate. On the other hand, TrPepz, which had no effect on N-benzoyl-L-tyrosine ethyl ester, hydrolyzed N-tosyl-L-arginine methyl ester with a Km value that was essentially identical to that of trypsin, but its kcat value was almost half that of trypsin. TrPepz was fully inactivated by reduction of the disulfide bond, by DIFP, or by phenylmethylsulfonyl fluoride but not by TPCK. It was also completely inhibited by soybean trypsin inhibitor, bovine pancreatic trypsin inhibitor, and human alpha 1-antitrypsin. ChPepz and TrPepz hydrolyzed proteins (myoglobin and casein) to give panels of peptides that were similar to those of the same protein obtained with the respective enzyme. However, TrPepz was more efficient than trypsin at hydrolyzing the C bonds of two or more consecutive lysine and/or arginine residues. Like its esterase activity, the proteolytic activity of ChPepz was inhibited by either DIFP or TPCK whereas that of TrPepz was inhibited by either DIFP or phenylmethylsulfonyl fluoride but not by TPCK. Finally, ChPepz and TrPepz were each more active at low temperature than the respective enzyme. This ability to construct fully functional peptide enzymes (pepzymes) of chosen specificities should find many practical applications. PMID- 8367495 TI - Alterations in phenotypic biochemical markers in bladder epithelium during tumorigenesis. AB - Phenotypic biochemical markers of oncogenesis and differentiation were mapped in bladder biopsies to investigate changes that occur in bladder tumorigenesis and to identify markers for increased bladder cancer risk. Touch preparations from biopsy specimens from 30 patients were obtained from tumors, the adjacent bladder epithelium, and random distant bladder epithelium. Markers, including DNA ploidy, epidermal growth factor receptor (EGFR), and oncoproteins, were quantified in individual cells by using quantitative fluorescence image analysis. Cluster analysis revealed the markers fell into three independent groups: (i) G-actin and EGFR; (ii) ploidy, cytology, and p185 (HER-2/neu oncoprotein) (ERBB2); and (iii) p300, a low-grade tumor antigen. Each marker displayed a gradient of abnormality from distant field to adjacent field to tumor. Different patterns for each marker suggested a developmental sequence of bladder cancer oncogenesis; G-actin was altered in 58% of distant biopsies (vs. 0/6 normals, P < 0.001), ploidy and cytology were altered in < 20% of distant fields and approximately 80% of tumors, and the other markers were intermediate. Patterns of EGFR and p185 suggest low and high-grade tracks diverge early (P < 0.05 by Mann-Whitney U test for EGFR and ANOVA for p185). In conclusion, this study shows that a sequence of phenotypic changes accompanies development and progression of bladder cancers. Biochemical alterations in cells of the bladder field are often detectable before abnormal pathology, and markers previously thought to be limited to tumors were found in the field. The hierarchy of expression may be useful in identifying high-risk patients, assessing completeness of response to therapy, and monitoring and predicting recurrence. PMID- 8367496 TI - Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9. AB - Virulence of the human malaria parasite Plasmodium falciparum is believed to relate to adhesion of parasitized erythrocytes to postcapillary venular endothelium (asexual cytoadherence). Transmission of malaria to the mosquito vector involves a switch from asexual to sexual development (gametocytogenesis). Continuous in vitro culture of P. falciparum frequently results in irreversible loss of asexual cytoadherence and gametocytogenesis. Field isolates and cloned lines differing in expression of these phenotypes were karyotyped by pulse-field gel electrophoresis. This analysis showed that expression of both phenotypes mapped to a 0.3-Mb subtelomeric deletion of chromosome 9. This deletion frequently occurs during adaptation of parasite isolates to in vitro culture. Parasites with this deletion did not express the variant surface agglutination phenotype and the putative asexual cytoadherence ligand designated P. falciparum erythrocyte membrane protein 1, which has recently been shown to undergo antigenic variation. The syntenic relationship between asexual cytoadherence and gametocytogenesis suggests that expression of these phenotypes is genetically linked. One explanation for this linkage is that both developmental pathways share a common cytoadherence mechanism. This proposed biological and genetic linkage between a virulence factor (asexual cytoadherence) and transmissibility (gametocytogenesis) would help explain why a high degree of virulence has evolved and been maintained in falciparum malaria. PMID- 8367498 TI - Heterogeneity of the principal sigma factor in Escherichia coli: the rpoS gene product, sigma 38, is a second principal sigma factor of RNA polymerase in stationary-phase Escherichia coli. PMID- 8367497 TI - Phospholipase A2 activity can protect renal tubules from oxygen deprivation injury. AB - During hypoxic or ischemic renal tubular injury, phospholipase A2 (PLA2) induces membrane deacylation, causing fatty acid accumulation and phospholipid breakdown. Because these changes can compromise cellular integrity, PLA2 activity has been widely proposed as a critical mediator of hypoxic renal tubular injury and, hence, of ischemic acute renal failure. To explore this hypothesis, isolated rat proximal tubules were subjected to continuous oxygenation or to hypoxic injury with or without exogenous PLA2 addition (porcine or bovine pancreatic PLA2; bee or snake venom PLA2). Cell death was quantified by lactic dehydrogenase (LDH) release. Pancreatic PLA2 (0.4 unit/ml) caused no LDH release under oxygenated conditions, and it dramatically attenuated hypoxic cell death (e.g., no PLA2, 55 +/- 3% LDH release; porcine pancreatic PLA2, 22 +/- 1% LDH release; P < 0.001). Bee and snake venom PLA2 (0.4 unit/ml) were directly toxic to tubules under oxygenated conditions, and this injury was additive with that induced by hypoxia. However, when these venoms were serially diluted (removing their overt toxicity), they, too, mitigated hypoxic cell death (LDH release with PLA2, 33 +/- 2%; without PLA2, 60 +/- 1% LDH release; P < 0.001). PLA2-mediated cytoprotection was Ca2+ dependent (negated by Ca2+ chelation), and it was expressed despite worsening hypoxia-associated membrane deacylation/fatty acid accumulation (12 times) and ATP depletion. These results indicate that PLA2 activity can exert both beneficial and deleterious effects on O2-deprived renal tubules, the net result of which can be a salvaging of cells from hypoxic cell death. PMID- 8367499 TI - [The importance of information for professionals. A study of Italian nursing journals]. PMID- 8367500 TI - [The prevention of urinary infections associated with bladder catheterization: the use of the preconstituted kit and of the sterile closed-circuit bag. The role of the nurse epidemiologist]. PMID- 8367502 TI - [The file for "personalized delivery": a presentation of experience. The S. Maria della Misericordia Hospital--the Nursing Service. A nursing guide to data collection]. PMID- 8367501 TI - [The living conditions of the elderly in the reality of San Daniele del Friuli]. PMID- 8367503 TI - Is this commercialism gone mad? PMID- 8367504 TI - A one-to-one relationship with lasting benefits. Implementing primary nursing in a coronary care unit. AB - It is essential that people who have suffered a myocardial infarction are counselled on how to avoid repeated attacks. By implementing primary nursing in a coronary care unit, the one-to-one relationship involved can be used to enhance the counselling process. PMID- 8367505 TI - Simply a case of good practice. Avoiding catheter-related sepsis in total parenteral nutrition. AB - Catheter-related sepsis is a well-known complication associated with the administration of total parenteral nutrition. A strict aseptic approach, supplemented with a knowledge of how the infection occurs, will do much to avoid this problem. PMID- 8367506 TI - Gene therapy: the dawn of a revolution. AB - Gene therapy offers the hope of effective treatment for thousands of people with genetic diseases, such as diabetes and muscular dystrophy. Early research looks promising, but doubts about its safety remain. PMID- 8367507 TI - How antibiotics work: protein synthesis. AB - 1. Antibiotics are important agents for the treatment of infections. 2. They are special chemicals produced by a few species of microorganisms which inhibit the growth of other micro-organisms. 3. They inhibit growth by attacking one of five sensitive sites. 4. A selection of antibiotics attacking the protein synthesis mechanism are identified and their modes of action described. PMID- 8367508 TI - Waterlow card. PMID- 8367509 TI - Paracetamol overdose. PMID- 8367510 TI - A concept for all the family. Family centred care: a concept analysis. AB - Family centred care is now perceived as fundamental to meeting hospitalised children's physical and emotional needs. It is important, however, that nurses fully understand the concept or it may be implemented more with the intention of meeting ward goals than family needs. PMID- 8367511 TI - Evaluation of a semipermeable polyurethane absorptive dressing. AB - While semipermeable film dressings are well established for treatment of moist wounds, they lose moisture to the atmosphere at a fixed rate. This article reports an evaluation of a semipermeable dressing recently made available in the UK which claims to vary the rate of moisture vapour loss. PMID- 8367512 TI - Steps to develop a working relationship. An evaluation of the community-based clinical nurse specialist. AB - To establish an effective working relationship between community nurses and clinical nurse specialists (CNSs) working in the community, the role of the CNS must be clearly defined. A survey was undertaken to identify CNSs' and district nurses' attitudes to the role and its requirements. The ensuing recommendations were implemented with positive results. PMID- 8367513 TI - A heady mixture of freedom and responsibility. Rural community nursing in New Zealand. AB - Working as a community nurse in a rural setting has its obvious attractions. A community health nurse based in New Zealand describes the pleasures and challenges involved. PMID- 8367514 TI - Provision to reflect real needs. Meeting the needs of disabled people in general practice. AB - Implementation of the Community Care Act makes it essential that clients' needs for services are accurately assessed. A study was undertaken by a general practice to identify whether clients with physical disabilities were satisfied with the service they received. PMID- 8367515 TI - Is caring a myth? PMID- 8367516 TI - [The biochemical basis of toxic actions of drugs and other xenobiotics]. PMID- 8367517 TI - Effect of frequency and conductivity on field penetration of electromagnetic hyperthermia applicators. AB - The field penetration of electromagnetic hyperthermia applicators in 2.5-29 g l-1 saline (NaCl) solutions over a range of frequencies is investigated. Calculated field penetration based on the current-element method agrees well with measurement at frequencies above about 100 MHz, but at lower frequencies measured field penetration becomes progressively less than calculated as conductivity is reduced. Experimental results and finite-difference time-domain (FDTD) method modelling show that the electromagnetic field produces circulating currents. The effect of these circulating currents on the heating pattern of the applicators should be considered when planning hyperthermia treatment. PMID- 8367519 TI - A statistical model for the determination of the optimal metric in factor analysis of medical image sequences (FAMIS). AB - A statistical model is added to the conventional physical model underlying factor analysis of medical image sequences (FAMIS). It allows a derivation of the optimal metric to be used for the orthogonal decomposition involved in FAMIS. The oblique analysis of FAMIS is extended to take this optimal metric into account. The case of scintigraphic image sequences is used. We derive in this case that the optimal decomposition is obtained by correspondence analysis. A scintigraphic dynamic study illustrates the practical consequences of the use of the optimal metric in FAMIS. PMID- 8367518 TI - Constrained least-squares restoration and renogram deconvolution: a comparison with other techniques. AB - It has previously been shown that an iterative constrained least-squares (CLSR) technique using a noise-based constraint may be superior to other methods of renogram deconvolution analysis. To test this hypothesis on real data, renography was performed on 70 patients with established diagnoses of normal, insufficient or acutely obstructed kidneys. Standard renography parameters were obtained from the time activity curves which were then deconvolved using three techniques. One kidney per patient was chosen at random for analysis resulting in a total of 43 normal and 27 diseased kidneys. The ability of each of the analytical techniques to discriminate between normal and diseased kidneys was assessed using logistic regression. CLSR proved to be robust and provide the best discrimination of the deconvolution techniques. However, the best overall discrimination was provided by a model based on the renography parameters excretion ratio, rate of uptake and time to peak activity which correctly classified 86% of the kidneys. It is possible that the renogram parameters could be used to produce notional probabilities of renal dysfunction which the physician could use as an aid in the interpretation of gamma-camera renography. PMID- 8367520 TI - A facility for biomedical experiments with thermal neutrons. AB - The Studsvik thermal-neutron facility was originally designed for neutron capture radiography (NCR) at high thermal-neutron fluence and low fast-neutron contamination. It has now been modified to permit irradiation of living cells and animals without the need for stopping and restarting the R2-0 reactor. Previous calculations of the thermal-neutron intensity at the NCR position were performed using the two-dimensional diffusion theory code DIXY. In this report the Monte Carlo program MCNP 3B is used to calculate the neutron fluence at the radiography position, and neutron and photon fluences at the positions of the cell specimens. The normalized neutron fluences from the calculations agree well with measured values and show that the contamination with high-energy neutrons is low. The agreement between measured and calculated photon doses was reasonable. The thermal-neutron fluence rate is (2.3 +/- 0.1) x 10(9) cm-2 s-1 at 100 kW at the NCR position and (0.96 +/- 0.03 x 10(9) cm-2 s-1 at 100 kW at the front plate of the loading tube. The photon dose is about (1.6 +/- 0.2) x 10(-12) Gy per neutron. Survival curves of V79 cells grown as monolayers and irradiated in the thermal neutron beam, with and without boron, are presented. PMID- 8367521 TI - Quantitative neutron capture radiography for boron in biological specimens. AB - Track-etch detectors made of cellulose nitrate (LR 115, Kodak Pathe) and polycarbonate (CR 39, Pershore Mouldings Ltd) were compared regarding sensitivity and background when used as detectors for boron determination in biological samples. Measurements were made on two kinds of sample, cryosectioned biological tissue, and liquid samples deposited directly on the detector surface as microdroplets. The CR 39 films were pretreated or washed before irradiation. When cryosectioned tissue was used, measurements were made with and without the inclusion of Mylar foils between the samples and the detectors. Foil thicknesses used were 2 microns in the case of LR 115 and 2, 4, and 6 microns in the case of CR 39. All samples were irradiated with a thermal-neutron fluence of 5 x 10(12) neutrons cm-2 at the thermal-neutron facility in Studsvik, Sweden. The use of a Mylar foil generally suppressed the background tracks relative to the tracks from the 10B disintegration. No difference in resolution between CR 39 and LR 115 was observed. Pretreatment of the CR 39 resulted in an improved sensitivity of detection but the detector became saturated at 0.25 parts per million of 10B. The background was found to be lower in the pretreated detector. PMID- 8367522 TI - In vivo measurement of the low-frequency dielectric spectra of frog skeletal muscle. AB - Capacitance, conductance and dielectric loss spectra are obtained, in vivo, for a number of electrode separations in the gastrocnemius muscle of a frog. At each frequency the reciprocals of these parameters are plotted versus electrode separation. From the slopes of the resulting lines the complex permittivity and the conductivity of the muscle can be determined, with electrode effects eliminated. The sequence of power-law responses which is found is consistent with the fractal model proposed by Dissado. The electrical properties measured in vivo with needle electrodes are similar to those measured with surface electrodes for frequencies between 1 kHz and 1 MHz. PMID- 8367523 TI - Measuring astatine-211 distributions with SPECT. AB - We have investigated standard SPECT techniques (rotating gamma cameras, multi hole collimators, and filtered backprojection reconstruction) for imaging astatine-211 distributions. Since 211At emits alpha particles, this nuclide has potential for use in radiotherapy. The capability of imaging this nuclide would allow in vivo evaluation of the distribution and stability of potential 211At labelled radiotherapeutic agents. 211At decay yields x-rays in the 77-92 keV range in addition to 500-900 keV gamma rays. This study evaluates the feasibility of SPECT imaging using the x-ray emissions of 211At. We have evaluated several collimators, with the determination that the medium-energy collimators we used are suitable, with 7% penetration (uncollimated counts versus collimated counts). Several phantoms were imaged and attenuation coefficients were measured (narrow beam mu = 0.182 cm-1 for 77-80 keV x-rays in water). Reconstructed images demonstrate qualitative capabilities and a simple quantitative study demonstrates good correction for attenuation and scatter (approximately 10% error), at low count densities, at least for the phantom geometries used in this study. PMID- 8367524 TI - Normalized organ dose data measured as a function of field size for abdominal examinations. AB - Doses to 14 radiosensitive organs were measured as a function of field size for both antero-posterior (AP) and postero-anterior (PA) projections of the abdomen. The organ doses were measured using thermoluminescent dosemeters (TLD) placed within a Rando anthropomorphic phantom. Circular field sizes 14 cm, 26 cm and 36 cm in diameter (measured at the image intensifier input plane) were set for the PA irradiations. For the AP projections, the circular field sizes measured 14 cm, 20 cm, 27 cm and 40 cm in diameter, again specified at the input plane of the image intensifier. Organ doses were also measured for the conventional 35 x 35 cm film/screen technique, for both AP and PA views. The dose measurements were made at a tube potential of 81 kV, which is commonly used in radiological examinations of the abdomen. TLD were also used to measure the entrance surface dose (with backscatter) for each field size and projection. The organ doses are presented normalized to this entrance surface dose. A brief comparison is made between the data measured in the current study and normalized organ dose data published by other authors. PMID- 8367525 TI - Design of a californium-based epithermal neutron beam for neutron capture therapy. AB - The potential of the spontaneously fissioning isotope, 252Cf, to provide epithermal neutrons for use in boron neutron capture therapy (BNCT) has been investigated using Monte Carlo simulation. The Monte Carlo code MCNP was used to design an assembly composed of a 26 cm long, 11 cm radius cylindrical D2O moderator followed by a 64 cm long Al filter. Lithium filters are placed between the moderator and the filter and between the Al and the patient. A reflector surrounding the moderator/filter assembly is required in order to maintain adequate therapy flux at the patient position. An ellipsoidal phantom composed of skull- and brain-equivalent material was used to determine the dosimetric effect of this beam. It was found that both advantage depths and advantage ratios compare very favourably with reactor and accelerator epithermal neutron sources. The dose rate obtainable, on the other hand, is 4.1 RBE cGy min-1, based on a very large (1.0 g) source of 252Cf. This dose rate is two to five times lower than those provided by existing reactor beams and can be viewed as a drawback of using 252Cf as a neutron source. Radioisotope sources, however, do offer the advantage of in-hospital installation. PMID- 8367526 TI - Calibration of the NPL secondary standard radionuclide calibrator for 192Ir brachytherapy sources. AB - Safe and effective treatment with brachytherapy sources requires an accurate knowledge of the local tissue absorbed dose rate derived from the source reference air kerma rate. It is desirable that these air kerma rate measurements be traceable to national standards. The NPL has embarked on a programme that will enable the user to assay brachytherapy sources in a convenient manner prior to treatment. Calibration figures have been derived for the NPL secondary standard radionuclide calibrator for 192Ir brachytherapy sources manufactured by Amersham International plc. The calibration figures enable the user to accurately estimate the reference air kerma rate and activity of such sources by measuring the ionization chamber response. Calibration figures for other brachytherapy sources are also being derived. PMID- 8367527 TI - Radiation dosimetry using junction field-effect transistor detectors. AB - The use of junction field effect transistors (JFET) has been studied by connecting them in a bridge circuit. With a suitable back-up circuit, it was possible to measure doses as well as dose-rates. It was possible to alter the sensitivity of the JFET bridge by varying the biasing components of the JFET. Easy temperature compensation was also possible. However, response of the JFET to radiation showed energy dependency similar to that of semiconductor diodes. PMID- 8367528 TI - Liposomal delivery of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD), to tumor tissue in a mouse tumor model. AB - Biodistribution studies were carried out on 14C-labeled benzoporphyrin derivative monoacid ring A (BPD), which had been formulated as a unilamellar liposome or taken from a stock solution in dimethyl sulfoxide diluted into phosphate-buffered saline immediately before intravenous injection into DBA/2 mice. By and large the general distribution of BPD to various organs and tissues was comparable for both formulations. It was noted, however, that liposomal material appeared to enter tissues more rapidly and to be cleared more rapidly, as demonstrated by shorter half-lives for a number of tissues including skin, lung and fat, and generally lower levels in most tissues 24 h following administration. Accumulation in tumor tissue was slightly higher with liposomal BPD, and clearance rates for this tissue were equivalent (half-lives 16.1 h for liposomal BPD and 16.9 h for aqueous BPD). When the two preparations were tested in a bioassay in tumor bearing mice, photodynamic therapy (PDT) with liposomal BPD proved to be superior to the aqueous preparation when PDT was administered 3 h following intravenous administration of BPD. Plasma distribution studies in vitro demonstrated that 91.1 +/- 0.3% of the liposomal BPD distributed to the lipoprotein fraction within the first hour of mixing, whereas only 49.1 +/- 2.6% of nonliposomal BPD was associated with lipoprotein under the same conditions. Furthermore, while lipoprotein-associated liposomal BPD distributed evenly between all three types of lipoprotein (high, low and very low density), a majority of nonliposomal BPD associated with the high-density lipoprotein fraction. PMID- 8367529 TI - The excitation of 8-methoxypsoralen with visible light: reversed phase HPLC quantitation of monoadducts and cross-links. AB - The formation of 8-methoxypsoralen-DNA monoadducts and cross-links is presumed to be responsible for the efficacy of photochemotherapies that employ 8 methoxypsoralen activated with long-wavelength ultraviolet radiation (UVA, 320 400 nm). In this report it is shown that 8-methoxypsoralen can also be activated with visible light (419 nm). Bovine aorta smooth muscle cells were treated with 8 methoxypsoralen (1,000 ng/mL) and 419 nm light (up to 12 J/cm2). Cellular DNA was isolated, hydrolyzed using nucleolytic enzymes and then analyzed by reversed phase high-performance liquid chromatography. The primary effect of using visible light instead of long-wavelength ultraviolet radiation is a more than 10-fold reduction in the extent of cross-link formation. Because the extent of monoadduct and cross-link formation has not been routinely measured in experiments in which cellular assays have been performed, it is difficult to correlate cell response to the presence of a particular type of 8-methoxypsoralen photoadduct (monoadduct or cross-link). Thus, the use of visible light allows the study of cells containing nearly 100% monoadducts. In addition, the reduction in cross-link formation when visible light is used to activate the compound may also reduce the mutagenicity of 8-methoxypsoralen and hence enhance its therapeutic efficacy. PMID- 8367530 TI - Cu(II) sensitizes pBR322 plasmid DNA to inactivation by UV-B (280-315 nm). AB - Copper(II), in the presence of UV-B radiation (280-315 nm), can generate single strand breaks in the sugar-phosphate backbone of pBR322 plasmid DNA. A low level of single-strand backbone breaks occurs in the presence of Cu(II) alone, but UV-B irradiation increases the rate by the more than 100-fold. Concomitant with the damage to the DNA backbone is a loss of transforming activity. Oxygen is required for generation of the single-strand breaks but not for the loss of transforming activity. A DNA glycosylase (Fpg), which participates in the repair of certain DNA nitrogenous base damage, does not repair plasmid DNA damaged by Cu(II). The hydroxyl radical scavenging compound DMSO is only somewhat effective at protecting the physical and biological properties of the DNA. These results with Cu(II) are compared to those obtained previously with pBR322 plasmid DNA in the presence of Fe(III) and UV-A. PMID- 8367531 TI - Long-wavelength UVA radiation induces oxidative stress, cytoskeletal damage and hemolysis. AB - We investigated the ability of the different wavelength regions of UV radiation, UVA (320-400 nm), UVB (290-320 nm) and UVC (200-290 nm), to induce hemolysis. Sheep erythrocytes were exposed to radiation from either a UVA1 (> 340 nm) sunlamp, a UVB sunlamp, or a UVC germicidal lamp. The doses used for the three wavelength regions were approximately equilethal to the survival of L5178Y murine lymphoma cells. Following exposure, negligible hemolysis was observed in the UVB- and UVC-irradiated erythrocytes, whereas a decrease in the relative cell number (RCN), indicative of hemolysis, was observed in the UVA1-exposed samples. The decrease in RCN was dependent on dose (0-1625 kJ/m2), time (0-78 h postirradiation) and cell density (10(6)-10(7) cells/mL).. Hemolysis decreased with increasing concentration of glutathione, hemoglobin or cell number, while the presence of pyruvate drastically enhanced it. Because scanning spectroscopy (200-700 nm) showed that hemoproteins and nicotinamide adenine dinucleotides were oxidized, cytoplasmic oxidative stress was implicated in the lytic mechanism. Further evidence of oxidation was obtained from electron micrographs, which revealed the formation of Heinz bodies near the plasma membrane. The data demonstrate that exposure of erythrocytes to UVA1, but not UVB or UVC, radiation causes oxidation of cytoplasmic components, which results in cytoskeletal damage and hemolysis. PMID- 8367532 TI - Effects of mutagenetic substitution of prolines on the rate of deprotonation and reprotonation of the Schiff base during the photocycle of bacteriorhodopsin. AB - Membrane-buried proline residues are found in many transport proteins. To study their roles in the structure and function of bacteriorhodopsin (bR), effects of the individual substitutions of Pro-50, Pro-91 and Pro-186 on the deprotonation and reprotonation kinetics of the Schiff base (SB) were determined by flash photolysis. The obtained rate constants and the amplitudes of the slow and fast components were compared with those of ebR (wild-type bR, the native protein that is expressed in Escherichia coli). The deprotonation rates of PSB were found to be 10 times faster than that of ebR for P50A, P91A and P91G mutants, and 4 times faster for the P50G mutant. These mutations also increased the initial reprotonation rate of the SB, although the overall change in the reprotonation rate is not as significant as that in the deprotonation rate. Our results indicate that Pro-50 and Pro-91, as well as Pro-186, are important for the proton pumping function of bR. PMID- 8367533 TI - Ocular light damage. PMID- 8367534 TI - Establishment and characterization of a monoclonal antibody recognizing the Dewar isomers of (6-4)photoproducts. AB - We established a monoclonal antibody (DEM-1) that recognizes UV-induced DNA damage other than cyclobutane pyrimidine dimers or (6-4)photoproducts. The binding of DEM-1 antibody to 254 nm UV-irradiated DNA increased with subsequent exposure to UV wavelengths longer than 310 nm, whereas that of the 64M-2 antibody specific for the (6-4)photoproduct decreased with this treatment. Furthermore, the increase in DEM-1 binding was inhibited by the presence of the 64M-2 antibody during the exposure. We concluded that the DEM-1 antibody specifically recognized the Dewar photoproduct, which is the isomeric form of the (6-4)photoproduct. The DEM-1 antibody, however, also bound to DNA irradiated with high fluences of 254 nm UV, suggesting that 254 nm UV could induce Dewar photoproducts without subsequent exposure to longer wavelengths of UV. Furthermore, an action spectral study demonstrated that 254 nm was the most efficient wavelength for Dewar photoproduct induction in the region from 254 to 365 nm, as well as cyclobutane dimers and (6-4)photoproducts, although the action spectrum values in the UV-B region were significantly higher compared with those for cyclobutane dimer and (6 4)photoproduct induction. PMID- 8367535 TI - Improved high-performance liquid chromatographic analysis of 8-methoxypsoralen monoadducts and cross-links in polynucleotide, DNA, and cellular systems: analysis of split-dose protocols. AB - The distribution of 8-methoxypsoralen-thymidine photoadducts from polynucleotides, calf thymus DNA and mammalian cells treated with [3H]8 methoxypsoralen under a variety of irradiation conditions was determined using high-performance liquid chromatography and scintillation analysis. The split-dose protocol, with samples treated with 8-methoxypsoralen and low doses of long wavelength UV radiation to generate monoadducts, washed to remove unreacted 8 methoxypsoralen, then irradiated further to convert the monoadducts to cross links, was examined. The photoadduct distribution in the first step is dependent upon the UVA dose and the wavelength of the radiation, but it is relatively independent of 8-methoxypsoralen concentration. Low fluence and longer wavelengths generate mainly 4',5'-monoadducts, whereas higher fluences and shorter wavelengths yield more cross-links. The second irradiation step converts the 4',5'-monoadducts to cross-links as well as to 3,4-monoadducts. The overall yield of cross-links after the second irradiation step is not dependent upon the wavelength used in the first step. Cellular studies demonstrated that the split dose protocol is applicable to mammalian systems. These results may affect the interpretation of mutagenesis studies based on the split-dose protocol, because the second step can convert 4',5'-monoadducts to both 3,4-monoadducts, the expected cross-links. Therefore, interpretations that link increases in mutagenicity after the second step in a split-dose study solely to cross-link formation may need re-examination. PMID- 8367536 TI - A pulsed photolysis procedure for determining oxygen equilibrium parameters of low-affinity noncooperative hemoglobins. AB - It is often very difficult to obtain precise values for oxygen equilibrium constants for low-affinity noncooperative hemoglobins owing to the ease with which they are oxidized and denatured with even the most gentle stirring or agitation. We have developed a procedure that eliminates this problem by maintaining the hemoglobin as HbCO except during the brief time it is present as Hb, and HbO2 forms following photolysis. Oxygen is continuously removed by an enzyme system. The solution is photolyzed to 100% every 2-3 min during the deoxygenation process to obtain maximum absorbance changes at the Hb-HbCO isosbestic. These maximum absorbance changes at known times during the deoxygenation provide the necessary data for obtaining the oxygen equilibrium constant. These absorbance changes are used with enzyme kinetics equations to obtain calculated times. The simple equations, which neglect heme concentration, will be satisfactory for nearly all conditions, but for generality the complete equations are given. The variance minimizations are with respect to observed and calculated photolysis times. The results for native carp Hb over a range of temperatures are in excellent agreement with results obtained with considerably more material and greater difficulty by other methods. PMID- 8367537 TI - Laser-induced fluorescence in malignant and normal tissue of rats injected with benzoporphyrin derivative. AB - Laser-induced fluorescence was used to characterize the localization of intravenously administered benzoporphyrin derivative-monoacid (BPD-MA) 3 h postinjection in different rat tissue types, including an induced experimental malignant tumor. A comparison of the fluorescence properties and demarcation potential between the newer sensitizer BPD-MA and four other substances, hematoporphyrin (HP), polyhematoporphyrin ester (PHE), tetrasulfonated phthalocyanine (TSPc) and the commercially available Photofrin earlier investigated, is included. The fluorescence light was induced with a nitrogen laser, emitting at 337 nm. The fluorescence spectrum in the region 380-750 nm was analyzed by a polychromator equipped with a diode array detector. The demarcation potential between tumor and surrounding tissue in terms of fluorescence signal for the tumor model used was 2:1 for BPD-MA. In comparison with the other drugs, HP shows about the same demarcation potential, whereas Photofrin and PHE exhibit about 3 times better and TSPc about 1.5 times better demarcation. By also employing the endogenous tissue fluorescence signature the contrast was enhanced by a factor of about 2 for each of the five drugs. PMID- 8367538 TI - Inhibition of phthalocyanine-sensitized photohemolysis of human erythrocytes by quercetin. AB - Photohemolysis of erythrocytes in the presence of aluminum phthalocyanine tetrasulfonate as a sensitizer is inhibited by quercetin. D2O (98.5%) stimulated photohemolysis regardless of quercetin presence, suggesting the participation of singlet oxygen in the process. Since it has been shown that this flavonoid reacts with singlet oxygen, the protective effect might be attributed, at least partially, to its competitive reaction with singlet oxygen. At the molecular level, the alterations of membrane proteins that escort the process of photohemolysis, such as cross-linking of spectrin monomers and of other membrane proteins, were selectively inhibited by quercetin. This effect was qualitatively similar to that induced by NaF, suggesting that quercetin may, like NaF, also inhibit type I photooxidations, which contribute to hemolysis. The lipophilicity of quercetin seems to be an essential factor in the inhibition process; rutin, a water-soluble 3-rutinoside of quercetin, had only a negligible protective effect on photohemolysis. PMID- 8367539 TI - Membrane potential can influence the rate of membrane photomodification. AB - Though cellular photomodification has been shown to change cellular resting membrane potential, an effect of membrane potential on the rate of photomodification has never been reported. Here we demonstrate that the rate of photomodification of potassium channels in frog atrial cells is voltage dependent. The rate of potassium channel photomodification using negatively charged Rose Bengal as the photosensitizer is about 2.5 times greater at the resting membrane potential of -70 mV compared to +40 mV. Similar results are obtained using the positively charged photosensitizer methylene blue. On the other hand, the rate of photomodified increase of leak current in the same cells does not significantly change in this voltage range with Rose Bengal as photosensitizer, but demonstrates a voltage dependence like that of potassium current when methylene blue is the photosensitizer. These observations cannot be explained based on voltage-dependent partitioning of the sensitizer, as similar effects on potassium current were obtained using either a positively charged or negatively charged sensitizer. PMID- 8367540 TI - [Endangerment by the environment--on the origin and psychopathology of environmental anxiety]. AB - Characteristics of the present ecological threat concerning the mind of men are described. Some psychiatric cases are given describing on one hand psychotic patients whose concern about the endangered natural environment is more accidental, whereas in other patients the feeling to be threatened has been resulted in psychopathological reactions of clinical importance. The impact of these new aspects of an ecological medicine is emphasized. PMID- 8367541 TI - [The "anxiety" ambulatory clinic: development and outlook]. AB - The study herewith represents the conception of the Bonn "anxiety"-ambulance, which was established in the University of Bonn, Department of Psychiatry, in January 1991. Besides we report our experiences from the first four months after opening of our ambulance and present first results. PMID- 8367542 TI - [Sexuality in acute psychiatric departments]. AB - Sexual behavior of patients in psychiatric admission wards is still only seldom spoken about, despite its relatively frequent occurrence in various forms and the emotional impact it bears on the psychiatric staff. The sexual issues have to be discussed with every patient. Among other things, the patients should be provided with information and the communicative meaning of his or her sexual manifestations should be elucidated and worked through psychotherapeutically. In the ward, a prohibitive attitude toward genital sexuality is justified; otherwise a flexible attitude should be assumed, which always takes the actual condition of the patient into consideration. PMID- 8367543 TI - [Young chronic psychiatric patients. A new focus in research and practice]. AB - This paper tries to show how stimulating the mutual effects of modeling, providing a network of psychiatric facilities and research can be in the care of young adult chronic patients. However, they do not behave all the same and require various strategies in therapy. Under the influence of a new model of Sheets et al. (1982), the young adult chronic patients are classified into three subgroups: the "High-Functioning, High-Aspiration"-, "Low-Energy, Low-Demand"- and the "High-Energy, High-Demand"-group. With the example of the situation in Berne it can be shown that each group needs different facilities. The own research allows conclusions about the efficacy of the therapeutic offers. On the other hand, it stresses the point that especially the group of "High-Energy, High Demand"-patients are a major challenge for us in psychiatry. Finally some reflections are presented how we professionals can deal with these patients in future to do more justice to them. PMID- 8367544 TI - [Deinstitutionalization of chronic psychiatric patients exemplified by a public psychiatric hospital]. AB - Basing on the multifarious phenomena of hospitalism in chronically mentally ill patients the authors report on a survey of known facts and analyses to enable focussing of appropriate on-target measures were taken to arrive at conclusions for caring for these long-term patients: 1. Fixing the deadline of the study; 2. Determining the quality of patient care; 3. Analysing the experiences collected in respect of the integrated training programme to promote cognitive, communicative and social abilities and skills among the patients in resident living quarters within the confines of the hospital. An attempt is made to arrive at an overall evaluation of the measures taken so far in respect of de hospitalisation and in building up complementary settlements outside the hospital but close to communal institutions. PMID- 8367545 TI - [Lithium and hyperthyroidism]. AB - The development of hypothyroidism and the forming of a goiter are well-known complications associated with lithium medications. But there are also occasional references to cases of hyperthyroidism in the wake of both continual and of discontinued lithium medication. In the case being reported on here of a lady patient aged 64 and suffering from a toxic adenoma not recognized at the time, thyrotoxicosis accompanied by above-normal FT-3 results and the characteristic clinical symptoms developed when lithium medication was discontinued. Medical literature consulted in the context discussed pharmacological mechanisms which may be responsible for the said complications. PMID- 8367546 TI - [Compulsory sterilization and euthanasia--on the origins of a development that lead to the Fascist management of psychiatric patients]. AB - When discussing and dealing with the way things went with German psychiatry during fascism the question arises constantly as to the scientific and theoretic self-interpretation of a specialist discipline that allowed itself to be misused without offering much resistance, if at all. The article makes an attempt to trace a few paths of specialist ideology at the turn of the 19th to the 20th century. The misuse of psychiatry and by psychiatry that has been practised both in the past and in the present cannot be understood if the guiding concepts of science generally ruling at the time are ignored. PMID- 8367547 TI - Self-defeating personality, depression, and suicidal ideation in adolescents. PMID- 8367548 TI - Drinking games and problems related to drinking among moderate and heavy drinkers. AB - The playing of drinking games, the quantity-frequency of alcohol consumption, and various problems related to drinking were assessed among a national sample of 3,830 alcohol consuming students from 58 American colleges and universities during the 1990-1991 academic year. Among Light-Moderate drinkers, a significantly higher proportion of students who had played a drinking game experienced 15 of 17 drinking-related problems. On the other hand, among Heavy drinkers there was little difference between game and nongame players. A higher percentage of game players had experienced five of the problems. Generally, for many problems, more than twice as many Heavy drinkers among both game and nongame players had exhibited the problem compared to more moderate drinkers. It was concluded that game playing appeared to increase problems related to alcohol primarily among more moderate drinkers whereas those who were heavy drinkers were exhibiting more problems regardless of their game-playing status. Education about the effect of game playing among students who are moderate drinkers should be addressed. PMID- 8367549 TI - On the validity of hypotheses derived from the Rorschach: the relationship between color and affect, update 1992. AB - A review of research since the last review in 1976 reconfirms the conclusion that how persons will express their emotions does not necessarily bear any relationship to the nature of their responses to color on the Rorschach. It is not only time for clinicians to give up this color-affect hypothesis with regard to Rorschach data but to conduct some basic, exploratory research to examine, empirically, whether a relationship does exist between persons' characteristic modes of expressing their emotions and their characteristic styles of responding to the Rorschach. PMID- 8367550 TI - Gender differences in attitudes toward science. AB - Analysis of nationwide surveys taken from 1972 through 1990 showed that, at all education levels and in all age groups from 20 to 79 years, females had less confidence in science than males. Greater percentages of females than males agreed with statements that, "science breaks down people's ideas of right and wrong" and "science pries into things." The relationships between gender differences in attitudes toward science and theories about biological differences in cognitive abilities between the sexes, traditional societal roles of women, and the impediments to participation of women in historically male-dominated science are discussed. PMID- 8367551 TI - Relation between humor and generativity. AB - Since humor has been found to facilitate such generative pursuits as psychotherapy, teaching, and nursing, and been associated with intimacy, it was hypothesized that high levels of humor are associated with high levels of generativity. The Measures of Psychosocial Development (measuring generativity), Situational Humor Response Questionnaire, and Coping Humor Scale were given to 56 subjects. Those scoring high on generativity scored significantly higher on both measures of humor than those scoring low in generativity. It was conjectured that humor may facilitate generativity through such mediating variables as intimacy and creativity as well as through stress reduction. PMID- 8367552 TI - Speculation contrasting experiences of World War II and U.S. servicemen of the Vietnam era in Southeast Asia. AB - Clinical experience with veterans leads to the speculation that there was deliberate promotion of drug use during the Vietnam War which may account for the markedly greater drug addiction evident in comparing Vietnam and World War II veterans. Returning home within a few days of combat rather than slowly by sea may have removed an opportunity to discuss and reflect on war experiences. PMID- 8367553 TI - Sex differences in romantic love attitudes among college students. AB - Previous research, using factor analysis, derived seven dimensions of romantic love. We sought to address whether these dimensions differed in importance for women and men. Specifically, it was hypothesized that women would consider Marriage and Family, Traditional Romantic Behavior, Routine Activities, and Religion, and men would consider Sexual Behavior, Aberrant Sex, and Drugs as more romantic. These specific predictions were seen as consistent with the 'double standard' regarding sex, i.e., it should be more important for men, and with an earlier theory we developed in which it was argued that in addition to the 'double standard' for sex, security-related stimuli should be more important for women. The results were entirely consistent with our predictions. PMID- 8367554 TI - Attitudes towards and observations of nonverbal communication in a psychotherapeutic greeting situation: III. An interview study of outpatients. AB - An interview study of 50 Swedish nonpsychotic outpatients treated by some kind of psychotherapy was performed to investigate their attitudes towards and observations of nonverbal communication in a greeting situation according to the Questionnaire on Nonverbal Communication (psychotherapy patients' version) in relation to background factors such as gender, age, education, and profession, interest in psychological matters, "reading articles and books in psychology," duration of professional help for psychological troubles, number of occasions waiting for a new therapist, and number of therapeutic sessions before the interview. The greeting situation was the first time a patient and a therapist met in a waiting room. Test-retest reliability of the questionnaire was larger for items about observation of nonverbal communication than for those about attitudes. Face communication (eye contact and smile) was considered by the subjects to constitute the most important nonverbal communication in the greeting process. The importance of the face in communication was stressed when the patient believed that such communication corresponded to more than 50% of the total communication in general, was female, was elderly, or reported special interest in nonverbal communication in the greeting situation. Some effects of bias were discussed. The analyses also showed a considerable consciousness and observation in the greeting situation by many psychotherapeutic outpatients. PMID- 8367555 TI - On choosing a baby's sex: what the future generation thinks, a preliminary survey. AB - The new biomedical techniques of reproduction, such as predetermination of a baby's sex, are gradually being initiated into formal practice in some countries such as Britain. This paper surveyed the attitudes of 60 academic and 60 nonacademic men and women between 18 and 20 years on whether they supported the idea of choosing a baby's sex. More than 75% of all participants rejected the idea of choosing a baby's sex, whilst only 20% agreed with the latter issue and a negligible number (4%) offered no opinion. Neither sex differences nor differences between academic/nonacademic population were significant. The results are discussed in relation to recent work on differences in attitudes between genders in academic and nonacademic settings. PMID- 8367556 TI - The adult who is an only child: achieving separation or individuation. AB - 60 women and 60 men between the ages of 18 and 45 years (M = 30.5, SD = 9.6) were categorized by sex, age, and birth order (only child, firstborn, lastborn) to assess the differences among the adult only-child, the youngest child, and the oldest child in autonomous characteristics and cohesiveness in family interaction. Analysis of the responses on a biographical data sheet, the California Psychological Inventory, and the Family Adaptability Cohesion Scales III showed that main effects for birth order and sex are significant in the process of separation-individuation and that the only child is less autonomous than the oldest child. PMID- 8367558 TI - Suicide and homicide rates and national character. PMID- 8367557 TI - Cognitive functioning, family history of alcoholism, and antisocial behavior in female polydrug abusers. AB - Family history of alcoholism and antisocial behaviour had both independent and synergic negative relationships with abstract verbal reasoning for a group of 42 female polydrug abusers whose main drug was heroin. This finding suggests that the observed lower cognitive performance may reflect the family history of alcoholism or antisocial behaviour rather than just drug abuse and is consistent with theories predicting a relative deficiency in high language skill by persons with antisocial personality disorders. PMID- 8367559 TI - Validation of a Portuguese form of Templer's Death Anxiety Scale. AB - To translate Templer's Death Anxiety Scale into the Brazilian Portuguese Escala de Ansiedade de Morte, linguistic validity was first established by back translation and calculating bilingual split-half reliability coefficients. Even numbered items achieved a minimally adequate .59, while the odd-numbered items attained a satisfactory .91. The internal consistency of the Escala (.77) matches that found for the original scale. The construct validity was tested by replicating the interactions of the English form with (1) the State-Trait Anxiety Inventory, (2) the Purpose-in-Life Test, and (3) Levenson's measure of locus of control. The Escala performed as expected, save for some difficulty with the locus of control measure. PMID- 8367560 TI - The influence of sex guilt on mood state following exposure to sexual stimuli. AB - 90 male subjects with high or low sex guilt were exposed to sexual music videos, rock videos, or a neutral travelogue before assessment of mood states. Scores on Elation, Vigor, and Aggression scales were significantly affected by video presentations when sex guilt was considered. PMID- 8367561 TI - Fluctuations in mood state and learning and retrieval. AB - The present study investigated whether learning and retrieval are associated with changes in mood state. 50 college students (20 men and 30 women) were assigned to one of five treatment conditions: Happy-Happy, Sad-Sad, Neutral-Neutral, Happy Sad, and Sad-Happy. Mood was induced via the Velten procedure. During the first mood-induction phase, students were exposed to a serial-learning task and recall trial, followed by a digit-symbol task. In the next phase, students were given a 5-min. muscle-relaxation exercise and a 5-min. distracting task. In the final phase, students underwent a second mood-induction phase, and a subsequent recall trial and digit-symbol task. Analyses indicated that recall was significantly greater in the Happy-Happy and Sad-Sad groups. Findings for the Neutral-Neutral group were mixed. Results are discussed in terms of support for the concept of context-related, mood-state-dependent recall. PMID- 8367562 TI - Contributions to the history of psychology: XCV. Possible relations between theories of evolution and animal learning. AB - It is proposed that the dominance of continuity learning theory as set against noncontinuity learning theory during the middle third of the 20th century rested importantly on its derivation from Darwin's theory of evolution. The kinship is shown in several ways. First, Thorndike and Hull echoed the principle of natural selection in their belief that behaviors underwent gradual modification because acts that were attended steadily by favorable consequences tended to occur with increasing frequency. Second, they denied both nonphysical explanations of behavior and a priori purposes which might guide that behavior. Third, the laws of learning were said to hold for all organisms. It is argued that the continuity approach may have enjoyed success because it was consistent with the Darwinian world view. Had punctualist, rather than gradualist, explanations of evolution come to the fore in the late 19th century, learning theories might have proceeded quite differently with the dominance of non-continuity approaches. PMID- 8367563 TI - Is smoking associated with height and weight? AB - The reported relationship between height and smoking was tested using data from a representative sample of the U.S. population (N = 41,014). Both height and weight were associated with smoking. A further analysis for males and females separately showed that the initial results were a result of confounding of the variables with gender. PMID- 8367564 TI - Assertiveness in Hispanic adolescents: relationship to alcohol use and abuse. AB - An investigation was carried out on the relation of assertiveness to use of alcohol among 3129 Hispanic junior high school students. Data were obtained through questionnaires administered in 47 public and parochial schools in New York City to 5501 students. An 18-item modified version of the Gambrill-Richey Assertiveness Inventory was used to assess assertiveness. Factor analysis of the inventory identified five assertiveness factors of substance awareness, mastery of cognitive skills, individual rights, dating, and social skills. Significant gender differences were observed. Multiple regression analysis showed that substance awareness was negatively associated with alcohol use while dating, social skills, and individual rights factors were positively associated with alcohol use. Acculturation with peers was also a significant predictor of alcohol use or abuse. The findings provide a basis for design of alcohol prevention programs that specifically focus on Hispanic youth. PMID- 8367565 TI - Personality disorders in geropsychiatric outpatients. AB - 36 geropsychiatric outpatients were administered a semistructured personality disorder interview derived from DSM-III criteria. Over half (58%) of this elderly sample met criteria for diagnoses of personality disorders, which have been shown to significantly affect treatment of Axis I symptomatology in young adults. Compared to a young adult outpatient sample of 298, older patients had significantly fewer disorders and multiple ones. The greater number of diagnoses yielded by the interview versus clinical evaluation approached statistical significance. PMID- 8367566 TI - Geophysical variables and behavior: LXXIII. Ubiquitous errors: a reanalysis of Anderson's (1987) "temperature and aggression". AB - Reanalysis of Anderson's 1987 data showed that correlations between number of hot days and violence shrank to nonsignificance when variables indicative of the South's subculture of violence were statistically controlled. The reanalyses also indicated that Anderson's results were unique to the procedures he used to select sociodemographic controls, operationalize temperature, and combine crime rates. It is concluded that relations described in a review of research on temperature and violence are neither ubiquitous nor effects. PMID- 8367567 TI - Validity issues in using the Millon-II with substance abusers. AB - This study addressed the use of the Millon Clinical Multiaxial Inventory-II (Millon-II) in assessing 73 substance abusers. The influence of neuropsychological functioning on personality functioning is discussed and evaluated. Reported history of substance abuse did not significantly relate to measures of neuropsychological or personality functioning. Of the sample, 16.9% produced invalid Million-II scores; invalidity was not significantly related to demographic characteristics or history of substance abuse. Millon-II profile validity was related to verbal and perceptual-motor functioning. Some neuropsychological variables significantly predicted Millon-II scale scores but with little consistency. PMID- 8367568 TI - Effects of feature variations on attributions for schematic faces. AB - 31 subjects classified 16 schematic faces on six dimensions. Attractiveness was generally associated with widely separated eyes, a short nose, and high feature placement. When features were considered in combination, faces with low placement were judged attractive, although the effect was mitigated by a narrow mouth. Previous findings concerning perceived age and gender were partially replicated, but folk wisdom linking intelligence to low placement (high forehead) was refuted. It is suggested that the relationship between individual features and attributions is nonlinear and interactive, and that researchers should investigate these hypotheses by exercising finer control over feature variations. PMID- 8367569 TI - Reports of childhood incest by adults with panic disorder or agoraphobia. AB - A convenience sample of 94 members of an agoraphobia self-help group responded to an anonymous survey on their possible histories of childhood incest. 12 (13%) respondents reported such a history. These results are discussed in terms of hypothesized etiologies of panic disorder and agoraphobia. PMID- 8367571 TI - The structure of Templer's Death Anxiety Scale among Egyptian students: a reply. PMID- 8367570 TI - Animal learning and motivation and addictive drugs. AB - Highlights of a systematic analysis of the abstracts of over 1700 publications dealing with addictive drugs (primarily alcohol) in the context of animal learning and motivation are summarized under two main headings. The behavioral effects of drugs vary with the nature of the drug, the dosage, and the behavioral baseline; behavioral tolerance frequently results from continued practice in the drug state. The paradigmatic effects show that drugs can function effectively as conditional stimuli, unconditional stimuli, responses, and reinforcers. As a result, drug habits develop their own motivational support, leading to conditioned tolerance and conditioned addiction. It is contended that principles of animal behavior can provide a basis for a theory of human drug use and abuse, but that voluntary control of addictive behavior requires uniquely human cognitive processes. PMID- 8367572 TI - Anomalies in covert conditioning. AB - The covert conditioning approach has received much empirical support. Despite the utility of this approach, a number of anomalies (or methodological problems) have been considered in the past. This study describes three anomalies in covert conditioning which have received little attention: (1) the difficulty in assessing the application of the covert conditioning technique by the client, (2) the difficulty in explaining client's failures during use of the technique in terms of either problems with the therapist's instructions regarding the use of the technique or problems with the client's inability to imagine the scene, and (3) the use of single-case experimental designs in the evaluation of the effectiveness of covert conditioning techniques seems to violate the experimental format of such designs. PMID- 8367573 TI - First memories are nonverbal and emotional, not necessarily talked about or part of a recurring pattern. AB - Nelson (1993) hypothesized that children must learn to verbalize their memories to retrieve them. Their parents talk with them about the experiences thereby influencing what is recalled. Further, recurrence of events indicate their importance and aids recall. To test these hypotheses, 83 students were asked to recall their first memory and indicate whether they recalled it verbally or nonverbally, had talked or been told about it, and whether it involved recurring events. They also were asked whether the memory involved emotions, because emotionality may enhance recall. Analysis showed that 94% of first memories were nonverbal and 92% involved an emotional event, but only 45% had been talked about and 55% were part of a recurring pattern. Research into nonverbal, first memories of adjusted individuals is needed to understand memory better and to have a comparison for what is recalled in therapy, in lawsuits involving child abuse, etc. PMID- 8367574 TI - The messiah-complex in schizophrenia. AB - After suggesting that religio-egocentricity and the messiah-complex may be a universal pattern in the psychoses, this paper briefly addresses three questions. First, in general, what is the relationship between religious emotions and schizophrenia? Second, why is it that the messiah-complex surfaces so often in the psychoses? Finally, what is the healthy dimension of religiosity? PMID- 8367575 TI - A comparison between scores on Kirton's inventory for nursing students and a general student population. AB - This study compared scores on the Kirton Adaption-Innovation Inventory of 60 first-year nursing students with scores of 73 nonnursing majors of approximately the same age to test the hypothesis that, in general, individuals selecting nursing as a major tend to show a more adaptive style of creativity in problem solving than their nonnursing peers. Analysis indicated the nursing students were significantly more "adaptive" in problem solving and less "innovative" than the nonnursing control group. PMID- 8367576 TI - Strategies of resistance by Type-A scoring Mexican-American college students. PMID- 8367577 TI - Alcohol use and abuse, suicide and homicide. PMID- 8367578 TI - Suicide and homicide rates during presidential terms as a function of economic conditions. PMID- 8367579 TI - Assessment of three-year-olds with the Stanford-Binet Fourth Edition. AB - The Stanford-Binet, Fourth Edition was normed for children 30 months of age and older, but its usefulness with young children (e.g., 36 months) has received little attention. This study of 121 three-year-old children examined possible administration problems, provided correlations with three environmental measures, and compared scores with those of the Peabody Picture Vocabulary Test--Revised. Problems of administration did arise on some subtests, correlations with environmental measures were moderate, and scores on the Stanford-Binet IV and PPVT-R were moderately correlated. The Stanford-Binet IV is a useful test in assessment of a broad range of intellectual abilities. PMID- 8367580 TI - A test of a social deviancy theory of suicide using the foreign born. PMID- 8367581 TI - The nature of schizotypy. AB - The matrix of intercorrelations between scales of schizotypy presented by Kendler and Hewitt in 1992 was reanalyzed, and results rather different from those reported by the original authors were found. The new structure shows good agreement with the theory of personality disorder published by Eysenck in 1987. In all, the different scales seem to fall into three groups or factors, identified as Neuroticism (N), Extraversion (E), and Psychoticism (P). It is doubtful if there is a common element left over once these three groups have been eliminated. PMID- 8367582 TI - Psychotherapy for Vietnam-related Posttraumatic Stress Disorder. AB - There are a wide range of psychotherapeutic treatments for Vietnam-related Posttraumatic Stress Disorder. This paper reviews some of the more commonly used interventions which are the behavioral, psychodynamic, family, and group therapies. Commonalities among these diverse treatments are shown to involve reconfronting trauma stimuli and the attempt to reintegrate traumatic experiences into ongoing personality functioning. It is shown that there are virtually no methodologically sound, empirically based studies that compare two or more treatments within a given study. Experimentally controlled, comparative studies are needed to advance our knowledge of effective treatments of this disorder. PMID- 8367583 TI - The critical mass theory of suicide. AB - It was reported in 1987 that nations with higher suicide rates in 1970 experienced greater increases by 1980. The present study did not replicate this phenomenon for the period of 1975 to 1985 using a sample of 32 nations with available data. PMID- 8367584 TI - Development of the ego and discomfort anxiety inventory: initial validity and reliability. AB - This article reports on four studies regarding the development, reliability, and validity of scales to measure two forms of anxiety, ego anxiety and discomfort anxiety. In the first study 140 undergraduates completed fourteen items related to ego anxiety and discomfort anxiety, as well as the Self-esteem Scale, the IPAT Anxiety Scale, and the Hopelessness Scale. Principal component analyses produced two factors, each with five items that showed differentiation between ego anxiety and discomfort anxiety. Guttman scales were developed from the items in the two factors. The resulting Ego Anxiety Scale had a coefficient of reproducibility of .94, a coefficient of scalability of .67 and estimated scale reliability of .84. The Discomfort Anxiety Scale had a coefficient of reproducibility of .91, a coefficient of scalability of .65 and estimated scale reliability of .83. Significant relationships were found between the scores on the two anxiety scales and scores on the Self-esteem Scale and the IPAT. Correlations between scores on the new anxiety scales and scores on the Hopelessness Scale were not significant. In the second study, undergraduates completed the Ego and Discomfort Anxiety Scales, the Self-esteem Scale, the IPAT Anxiety Scale, and the Hopelessness Scale. The reliability of the Ego Anxiety Scale (0.77) and the Discomfort Anxiety Scale (0.85) was estimated using Cronbach's alpha measure. t tests for scores of independent samples for students in Studies I and II were completed for scores on the Ego and Discomfort Anxiety Scales, Self-esteem Scale, IPAT Anxiety Scale, and Hopelessness Scale. None of these test comparisons were significant. The data from Studies I and II were pooled to provide tentative normative data for the Ego and Discomfort Anxiety Scales. The third study explored the reliability and validity of the new scales, testing 79 undergraduates who completed the Ego and Discomfort Anxiety Scales, the Fear of Negative Evaluation Scale, and the Problem Solving Inventory. The reliability coefficients of the Ego Anxiety Scale and Discomfort Anxiety Scale were 0.75 and 0.82, respectively. The differences between the combined scores of subjects in Studies I and II and the scores of subjects in the third study on the Ego and the Discomfort Anxiety Scale were not significant. A significant positive correlation, however, was found between scores on the Ego Anxiety Scale and scores on the Fear of Negative Evaluation Scale.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8367585 TI - Protection motivation theory and alcohol use attitudes among older adults. AB - Responses of 17 elderly persons and 20 VA inpatients with alcohol-abuse problems (all 60 yr. or older) to an Alcohol Attitude Survey administered by telephone and interview were examined. Inpatients felt more vulnerable, perceived higher costs in moderating drinking, and showed lower response efficacy. Inpatients consumed substantially more alcohol than the community-dwelling elders. Hypotheses for study were generated. PMID- 8367586 TI - Dosimetric effects of beam size and collimation of epithermal neutrons for boron neutron capture therapy. AB - A series of studies of "ideal" beams has been carried out using Monte Carlo simulation with the goal of providing guidance for the design of epithermal beams for boron neutron capture therapy (BNCT). An "ideal" beam is defined as a monoenergetic, photon-free source of neutrons with user-specified size, shape and angular dependence of neutron current. The dosimetric behavior of monoenergetic neutron beams in an elliptical phantom composed of brain-equivalent material has been assessed as a function of beam diameter and neutron emission angle (beam angle), and the results are reported here. The simulation study indicates that substantial differences exist in the dosimetric behavior of small and large neutron beams (with respect to the phantom) as a function of the extent of beam collimation. With a small beam, dose uniformity increases as the beam becomes more isotropic (less collimated); the opposite is seen with large beams. The penetration of thermal neutrons is enhanced as the neutron emission angle is increased with a small beam; again the opposite trend is seen with large beams. When beam size is small, the dose delivered per neutron is very dependent on the extent of beam collimation; this does not appear to be the case with a larger beam. These trends in dose behavior are presented graphically and discussed in terms of their effect on several figures of merit, the advantage depth, the advantage ratio, and the advantage depth-dose rate. Tables giving quick summaries of these results are provided. PMID- 8367587 TI - Hypertonic treatment during premature chromosome condensation allows visualization of interphase chromosome breaks repaired with fast kinetics in irradiated CHO cells. AB - A class of interphase chromosome breaks was visualized in irradiated (10 Gy) plateau-phase CHO cells after treatment (2-30 min) in hypertonic (500 mM NaCl) growth medium during the period normally allowed for chromosome condensation, in the premature chromosome condensation (PCC) assay. Rejoining of this class of interphase chromosome breaks was fast (t1/2 = 1.5 min) compared to the rejoining of interphase chromosome breaks normally observed in the absence of hypertonic treatment (t1/2 = 76 min), suggesting that they are formed from a different subset of precursor DNA lesions. A fast (t1/2fast = 12 min) and a slow (t1/2slow = 71 min) component were also observed in the rejoining of radiation-induced (50 Gy) DNA double-strand breaks (DSBs), as measured by pulsed-field gel electrophoresis. We propose that fast-repairing DSBs are the precursor lesions underlying the fast-repairing interphase chromosome breaks observed in these experiments. Slowly repairing DSBs are postulated to be the precursor lesions underlying the slowly repairing interphase chromosome breaks visualized using regular protocols for PCC. The visualization of fast-repairing interphase chromosome breaks achieved in these experiments is assumed to be due to a destabilization of chromatin by the hypertonic medium. This chromatin destabilization may cause either an inhibition of the rejoining of the fast component of DSBs during the period allowed for PCC or a transformation of a defined subset of fast-repairing DSBs into chromosome breaks. The latter hypothesis allows a more consistent interpretation of the available results. Transformation of a defined subset of fast-repairing DSBs to interphase chromosome breaks may be equivalent to damage fixation, and may correspond to the fixation of a form of PLD (beta-PLD) sensitive to treatment in hypertonic medium. PMID- 8367588 TI - Hypertonic treatment does not affect the radiation yield of interphase chromosome breaks in DNA double-strand break repair-deficient xrs-5 cells. AB - A DNA double-strand break (DSB) repair-deficient CHO cell line, xrs-5, was used to evaluate the effect of hypertonic treatment on the radiation yield of interphase chromosome breaks, as visualized by means of premature chromosome condensation (PCC). For this purpose, interphase chromosome breaks were measured in plateau-phase G1 cells after exposure to 10 Gy X rays using either the standard protocol for PCC induction or a revised protocol that includes a brief (20 min) treatment in hypertonic medium (500 mM NaCl) during chromosome condensation. Experiments at the chromosome level were complemented by experiments at the DNA and the cellular level performed under similar postirradiation conditions. The results obtained were compared to those reported previously for CHO cells. Radiation yields of interphase chromosome breaks, as measured using standard protocols for PCC induction, were higher in xrs-5 than in CHO cells. However, the yields became similar between the two cell lines when a 20-min incubation in hypertonic medium was introduced immediately after fusion with mitotic cells. This equalization was due to the fact that incubation in hypertonic medium did not affect the radiation yield of interphase chromosome breaks in xrs-5 cells but increased it in CHO cells to levels similar to those measured in xrs-5 cells. This result suggests that xrs-5 cells constitutively express as interphase chromosome breaks a subset of DSBs which in repair proficient CHO cells requires incubation in hypertonic medium for transformation to interphase chromosome breaks. Rejoining of DSBs, when measured in isotonic medium, was incomplete in xrs-5 cells compared to CHO cells. Rejoining of DSBs normally repaired in xrs-5 cells was completely inhibited during treatment in hypertonic medium. Postirradiation treatment in hypertonic medium affected the survival of xrs-5 cells only modestly, suggesting that the sector of PLD (beta PLD) which required treatment in hypertonic medium for fixation in repair proficient CHO cells is fixed constitutively in xrs-5 cells. These results are in agreement with a model developed to interpret results obtained in similar experiments with CHO cells (Iliakis et al., Radiat. Res 135, 160-170, 1993). The model postulates that potentiation in CHO cell killing induced by hypertonic treatment is caused by the transformation of a subset of fast-repairing DSBs to irreparable interphase chromosome breaks and assumes that this transformation is equivalent to fixation of beta-PLD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8367589 TI - The low carcinogenicity of electron radiation relative to argon ions in rat skin. AB - The carcinogenicity of electron radiation relative to argon ions in rat skin was examined, specifically investigating whether the linear-quadratic model is useful for predicting cancer yield for one type of radiation based on yields observed for a different type. Three experiments were conducted to obtain information on the relationship between cancer yield and the dose of electron radiation: (1) a conventional dose-response protocol where the number of rats per group was based on the expected tumor yield; (2) a multiple-fraction protocol designed to take advantage of yield additivity as a way to estimate carcinogenicity at lower doses; and (3) a protocol to examine the effect of age at the time of irradiation on the dose-response relationship for cancer induction. Published data on the induction of skin cancer in rats irradiated with electrons were reanalyzed and combined with results of the new experiments. Skin cancer yield versus dose for argon ions was consistent with the linear-quadratic model, but the cancer yield for electrons was considerably lower (by a factor of 6.7 at 10 Gy) than the prediction based on the linear-quadratic model. The cancer yield for electron radiation was better fitted by a dose-cubed power function than a linear quadratic function. The results indicate a substantially lower carcinogenic effectiveness for electron radiation, especially at lower doses, in comparison to argon ions and suggest that electrons may cause cancer by a three-event pathway instead of the two-event pathway that is consistent with the results for argon ions. PMID- 8367590 TI - Interphase death and reproductive death in X-irradiated MOLT-4 cells. AB - The killing effects of ionizing radiation on MOLT-4 cells were studied using colony formation assays, dye exclusion tests, and cell growth analysis. When MOLT 4 cells were exposed to X rays, the fraction of cells stained with erythrosin B increased markedly during the incubation after irradiation at 37 degrees C and reached a maximum within 24 h. In contrast, no such increase was observed for L5178Y cells or their derivative, radiosensitive mutant M10 cells, at a dose resulting in the same level of cell survival as measured by the colony formation assay. Detailed analysis of cell survival as measured by the dye exclusion test in comparison with that measured by the colony formation assay in MOLT-4 cells indicated that MOLT-4 cells are subject to interphase death as well as reproductive death. Analysis of subclones showed a wide variety of differences in the level of stained cells using the dye exclusion test. The results confirmed the population heterogeneity of MOLT-4 cells. Moreover, none of the subclones showed exactly the same cell survival when this was measured with the two assays. The present results strongly suggest that both modes of cell death may occur in single MOLT-4 cells. Possibly apoptosis is the mechanism accounting for both modes of death in these cells. PMID- 8367591 TI - Transgenic marrow transplantation: a new in vivo and in vitro system for experimental hemopoiesis and radiobiology which employs sequential molecular monitoring of multiple genetic markers. AB - Efforts to understand the in vivo regulation of hemopoiesis have been greatly impeded by an inability to trace and quantify the fate of multiple hemopoietic stem cell (HSC) cohorts within a single animal simultaneously. We report here the development of a molecular marker system which overcomes this deficiency and can be readily extended to a wide variety of applications in experimental hematology and radiobiology. Mixtures of HSC from multiple strains of transgenic mice, derived on a common genetic background, were used as donors to reconstitute lethally irradiated wild-type mice. Using molecular hybridization and the polymerase chain reaction, we documented the presence and quantified the amount of various transgenic markers in the blood of individual recipient mice after transplantation. The transgenic markers were also detected in spleen, thymus, peritoneal exudates, bone marrow, spleen colonies (CFU-S), and in vitro colonies. The transgenic transplantation marker system thus permits repeated analysis of multiple stem cell cohorts over the entire spectrum of hemopoiesis including HSC, intermediate precursors, and functionally mature cells. Therefore, the transgenic markers should facilitate the in vivo analysis of stem cell development, gene transfer, leukemogenesis, recovery from radiation or drug treatment, and the influence of hormones/growth factors on these processes. PMID- 8367592 TI - Analysis of large X-ray-induced mutant populations by denaturing gradient gel electrophoresis. AB - To increase the precision by which predominant point mutations can be observed, hypoxanthine guanine phosphoribosyl transferase (HPRT)-deficient mutants selected en masse from large X-irradiated cultures of human lymphoblastoid cells (line TK6) were analyzed by denaturing gradient gel electrophoresis (DGGE). Four independent experiments yielded approximately 7 x 10(3) and 3.2 x 10(3) initial surviving 6-thioguanine-resistant (6-TGr) mutants in X-ray-treated and untreated cultures, respectively. The hprt exon 3 fragments were amplified from DNA extracted from these mixed 6-TGr cell populations by employing the polymerase chain reaction using modified T7 DNA polymerase. DGGE was used to separate the mutant sequences from the wild-type as mutant/wild-type heteroduplexes. The X irradiated populations contained several mutant bands in the 104-bp low-melting region of exon 3 that were not observed in the untreated cultures. Two exon 3 specific mutations were observed in more than one treated culture and various tests for potential biases suggested that these were radiation-specific mutational hotspots. These two recurring mutations were specific 1-bp deletions in either a run of four T:A's (bp 294-297) or a run of 3 A:T's (bp 247-249). Several other "sporadic" signals observed in X-irradiated cultures were caused by small deletions ranging from 2 to 25 bp in length. PMID- 8367593 TI - Differential effects of fractionated X irradiation on mouse spermatogonial stem cells. AB - The response of spermatogonial stem cells to fractionated X irradiation was studied in the various stages of the spermatogenic cycle of the CBA mouse. Fractionated doses of 2 + 2, 1 + 3, and 3 + 1 Gy with a 24-h interval between the doses were compared with a single dose of 4 Gy. The numbers of undifferentiated spermatogonia present 10 days after (the second) irradiation were taken as a measure of stem cell survival. Twenty-four hours after the first irradiation a sensitization was observed that was found to be stage-dependent. The greatest sensitization occurred in that part of the spermatogonial stem cell population that was in stages X-I during the first irradiation, i.e., the part that is stimulated to proliferate or actively proliferating at that time. In stages that were quiescent during the first irradiation (VI-VII), fractionation did not influence the response. Therefore, only the spermatogonial stem cells that are initially radioresistant become sensitized 24 h after irradiation. When two unequal doses (3 + 1 Gy or 1 + 3 Gy) are given, damage correlates with the size of the second dose, indicating that priming doses of 1 and 3 Gy are both capable of inducing the sensitizing effect. PMID- 8367594 TI - Exonuclease I of Escherichia coli removes phosphoglycolate 3'-end groups from DNA. AB - Exonuclease I of E. coli is a 3'-->5' exonuclease acting on single-stranded DNA. We further demonstrate that the enzyme can remove phosphoglycolate groups at 3' termini in DNA. These types of lesions are introduced into DNA by agents that cause oxidative damage such as ionizing radiation. An oligonucleotide substrate pd(T)20[32P]dA was treated with acid to remove the adenine base to generate 3' termini containing 2-deoxyribose-5-phosphate end groups. This substrate was then treated with periodate to generate 3'-phosphoglycoaldehyde groups and was further oxidized with I2 to generate 3'-phosphoglycolate groups. The pd(T)20[32P]PGA substrate was annealed to pd(A)40-60 to produce a double-stranded substrate. Exonuclease I was effective in the removal of the 3'-phosphoglycolate groups from this substrate as determined by HPLC separation. With exonuclease III and endonuclease IV of E. coli, exonuclease I is the third activity found in E. coli that is able to excise deoxyribose-phosphate fragments at 3' termini in DNA. These sugar fragments are blocks to DNA polymerase, and their removal is necessary to complete the base excision repair process. PMID- 8367595 TI - Oncogene- transformed NIH 3T3 cells display radiation resistance levels indicative of a signal transduction pathway leading to the radiation-resistant phenotype. AB - Oncogenes and their normal counterparts, proto-oncogenes, are functionally important cellular genes which interact with one another as components of signal transduction pathways leading to cell growth and differentiation. Numerous reports in the literature have also begun to link these genes to the phenomenon of cellular radiation resistance. In this report we examine the radiation resistance level of NIH 3T3 cells transformed by various oncogenes in an attempt to define the intracellular pathway to the radiation-resistant phenotype. The results demonstrate that an analogous signaling pathway is apparently involved in acquisition of radiation resistance. Serine/threonine protein kinase oncogenes such as raf, mos, and PKC play a central role in the pathway. Moreover, specific oncogenes upstream (sis, HER-2, met, trk, and ras) and downstream (ets and myc) of these important signaling mediators can also influence the radiation resistance level of the cells. PMID- 8367596 TI - Systemic deposits of thorium in thorotrast patients with particular reference to sites of minor storage. AB - It is well established that injected Thorotrast is deposited in the liver, spleen, bone marrow, and lymph nodes, but accumulations in organs with lower macrophage activity have previously been given little attention. In this work, neutron activation analysis has been used to investigate concentrations of thorium in autopsy samples taken at sites of major and minor deposition in 24 Thorotrast patients. In the latter category, the highest values were found in the testis [40 x 10(-6) g/g(wet)], followed by those in the adrenal gland, gallbladder, lung, and pancreas. The resulting alpha-particle dose rates (mGy/year) are tentatively estimated to be 8.5 to the testis, 5.5 to the gallbladder, and 5.3 to the lung. These results may be relevant to the residual excess mortality among Thorotrast patients after diseases of the principal organs of deposition have been excluded; they also support previous indications that thorium deposited in pulmonary tissues is responsible for an important component of the total dose to the lung. In another context, our data may bear on the connection, postulated elsewhere, between exposure to alpha-particle emitters and elevated incidence of leukemia in the children of workers engaged in the reprocessing of nuclear fuel. PMID- 8367597 TI - Is there an adaptive response in spleen lymphocytes of C57B1/6 mice as assessed by chromosomal aberrations? AB - In previous publications we have shown that no adaptive response could be induced in preimplantation embryos and spleen lymphocytes of Heiligenberger mice, a strain inbred at our institute (Wojcik et al., Int. J. Radiat. Biol. 62, 177-186, 1992; Muller et al., Int. J. Radiat. Biol. 62, 169-175, 1992). Because of data indicating that some humans may be genetically deficient in the ability to express an adaptive response, we have speculated that the cells of the Heiligenberger strain may lack an adaptive response. To check this, experiments have been done with spleen lymphocytes of the C57B1/6 mice. Initial results indicated the presence of an adaptive response in some individual C57B1/6 mice. However, an analysis of aberration scores of parallel lymphocyte cultures revealed a high intraindividual variability, indicating that the adaptive response observed initially was a reflection of this variability rather than of induced radiation resistance. This conclusion is confirmed further by the lack of such variability in parallel cultures of lymphocytes from Heiligenberger mice. PMID- 8367598 TI - Deficits in the sensitivity of striatal muscarinic receptors induced by 56Fe heavy-particle irradiation: further "age-radiation" parallels. AB - We had previously shown that there was a loss of sensitivity of muscarinic receptors (mAChR) to stimulation by cholinergic agonists (as assessed by examining oxotremorine enhancement of K(+)-evoked release of dopamine from neostriatal slices) in animals that had been exposed to energetic particles (56Fe, 600 MeV/n), an important component of cosmic rays. This loss of mAChR sensitivity was postulated to be the result of radiation-induced alterations in phosphoinositide-mediated signal transduction. The present experiments were undertaken as a first step toward determining the locus of these radiation induced deficits in signal transduction by examining K+ enhancement of release of dopamine in 56Fe-exposed animals (0, 0.1, and 1.0 Gy) with agents [A23187, a potent Ca2+ ionophore, or 1,4,5-inositol trisphosphate (IP3)] that "bypass" the mAChR-G protein interface and by comparing the response to oxotremorine-enhanced K(+)-evoked release of dopamine. Results showed that although oxotremorine enhanced K(+)-evoked release of dopamine was reduced significantly in the radiation groups, no radiation effects were seen when A23187 or IP3 was used to enhance K(+)-evoked release of dopamine. Since similar findings have been observed in aging, the results are discussed in terms of the parallels between aging and radiation effects in signal transduction that might exist in the neostriatum. PMID- 8367599 TI - Reduced adriamycin concentration in rat mammary tumors treated previously with hyperthermia. AB - The effect of prior hyperthermia on the concentrations of adriamycin in tumors was examined. Chemically induced (9,10-dimethyl-1,2-benzanthracene) rat mammary adenocarcinomas were not heated or were heated one or two times (43.5 degrees C, 1 h; 24 h apart when two times) using an Nd:YAG laser. Rats were administered adriamycin (5 mg/kg, iv) 3 h after hyperthermia treatment. The concentrations of adriamycin in plasma and tissue were determined using high-performance liquid chromatography. Although plasma pharmacokinetics was unchanged by prior local hyperthermia, the concentration of adriamycin was significantly lower in tumors that had been heated previously compared to that in unheated tumors. Tumor blood flow rate was determined after an identical heating protocol using a reference sample technique with 113Sn microspheres. Tumor blood flow rate increased slightly during hyperthermia and then rapidly returned to control levels after hyperthermia. Decreased concentrations of adriamycin in tumors may result from biochemical changes induced by hyperthermia in neoplastic cells and may explain the adriamycin resistance in thermotolerant cells reported previously. PMID- 8367600 TI - [Endosonography of the esophagus and the stomach]. AB - Endosonography of the oesophagus and stomach is important for staging of carcinomas, for judging the degree of thickening of the wall, and for assessment of submucosal and intramural lesions and of space-occupying processes in extra oesophageal and extragastric organs. PMID- 8367602 TI - [Doppler echography for the preoperative assessment of malignant processes in the pancreas head and liver hilus]. AB - Ultrasound is the imaging technique of choice in obstructive jaundice for demonstration of dilatation of the bile ducts, and its position and cause. In carcinoma of the pancreatic head and in hilar tumours of the liver (Klatskin) it is often possible to demonstrate their inoperability, making other imaging techniques unnecessary. Duplex-Doppler ultrasound can be highly advantageous in the evaluation of compression or invasive growth of the tumour in the mesenterico portal venous system, making such invasive examination procedures as angiography unnecessary. PMID- 8367601 TI - [Intraductal ultrasound of the bile ducts]. AB - Intraluminal ultrasound with 12.5 and 20 MHz transducer allows precise analysis of the extrahepatic bile ducts and the adjacent structures. Inflammatory and malignant thickening of the bile duct wall can be assessed without difficulty. It is not possible, however, to differentiate between benign and malignant bile duct thickening, and for this purpose biopsy is required in addition. In tumor staging intraluminal ultrasound is superior to conventional ultrasound, because tumor infiltration into the adjacent tissues can be assessed and lymph nodes along the hepaticoduodenal ligament can be detected. Owing to the ultrasound frequencies available, local staging is limited to a circumference of 1.5/2 cm. Intraluminal ultrasound provides additional information that is useful in the diagnosis and therapy of bile duct stones and in different types of palliative tumor therapy. The procedure is simple and not too time consuming, and it involves no risks to the patient. PMID- 8367603 TI - [Sonography of acute appendicitis. A 5-year prospective study of 2074 patients. 2]. AB - High-resolution real-time ultrasound (US) with a 5 MHz transducer has proved to be an important method in the diagnosis of acute appendicitis. In a prospective study we examined 2074 unselected patients with suspected appendicitis to assess the diagnostic and epidemiological value of US. According to the clinical diagnosis females aged 10 to 30 represented the majority of suspected cases. Appendicitis was most often proved in male patients aged 15-30 years. The prevalence of acute appendicitis in childhood is lower (7%) than in elderly patients (33%). US enables the diagnosis of acute appendicitis with a sensitivity of 91%, a specificity of 98% and an overall accuracy of 97%. For differential diagnosis US demonstrates other diseases that mimic acute appendicitis. Thus it is possible to reduce the negative appendectomy rate particularly in children by revealing mesenteric lymphadenitis or terminal ileitis and in young women by directing attention to gynecological diseases. PMID- 8367604 TI - [Diagnosis of colonic tumors and chronic inflammatory colonic diseases by hydrocolonic sonography]. AB - Retrograde instillation of water into the colon makes it possible to visualize the colon sonographically from the rectosigmoid transition to the cecum in 97% of the patients examined. The sonographic views obtained using this technique, which is called hydrocolonic sonography, show the echo-free intestinal lumen, the five individual layers of the colon wall and the connective tissue surrounding the colon. Colonic polyps and carcinomas appear sonographically as echogenic structures projecting from the intestinal wall into the lumen. Colonic polyps larger than 7 mm diameter can be identified in 91% of cases, and the sensitivity of the technique in the detection of carcinomas of the colon is 97%. In addition, detailed evaluation of the structure of the bowel wall permits more precise staging of tumors of the colon. Aside from such localized changes, hydrocolonic sonography can also demonstrate typical changes in the wall structure in chronic inflammatory large-bowel diseases. In acute Crohn's disease the normal stratified appearance of the colonic wall is no longer in evidence and the wall appears visible thickened. In contrast, in patients with acute ulcerative colitis the normal sonographic stratified appearance of the colonic wall is maintained. Hydrocolonic sonography enables a detailed sonographic examination of the colonic lumen and the colon wall, thus providing additional information and allowing more precise diagnosis of many diseases of the colon. PMID- 8367605 TI - [Rectal endosonography for perirectal and non-tumor rectal changes]. AB - The value of rectal endosonography was retrospectively evaluated in 39 patients with various rectal and perirectal diseases. Endosonography proved to be very helpful in demonstrating or excluding abscesses. In patients with aspecific minor inflammatory rectal diseases, endosonography was not very helpful. Endosonography is complementary to other imaging techniques like CT and MRI in establishing perirectal tumors. Endosonography shows the relationship of the rectal wall with an extrarectal tumor and is capable of demonstrating the extent of smaller tumors. It may contribute to the diagnosis of endometriosis in the rectovaginal space. In patients with anal pain endosonography can play an important role in demonstrating or excluding fistulas, abscesses and other diseases. PMID- 8367606 TI - [2D-time-of-flight MR angiography in the diagnosis of abdominal aorta aneurysms]. AB - In abdominal aortic aneurysm ultrasonography, contrast-enhanced CT, and digital subtraction angiography (DSA) are the preoperative diagnostic methods of choice accepted today. It was the goal of this study to evaluate time-of-flight magnetic resonance angiography (MRA) in comparison with other radiographic procedures in different types of aneurysms. In 24 patients with proven aortic aneurysm, projection angiograms (MIP algorithm) of the abdominal aorta and pelvic arteries were performed using two-dimensional gradient echo multi slice sequence (FLASH, TE/TR = 10/51 ms; three slices; breathhold technique; flip angle = 30 degrees) in coronal orientation. In addition, renal arteries were imaged in axial slices. The information provided by MRA was comparable to that of DSA (perfused vascular lumen) and contrast-enhanced CT (alteration of vascular wall). Thus dilatation, thrombus, dissection, or inflammation could be analysed safely. Extension of the aneurysm to pelvic arteries could be evaluated in most cases by rotation of the projection angiograms; ostial renal artery disease could be visualized on axial slices. If further technical improvement of MRA is presupposed, this noninvasive method may completely replace the invasive procedures of contrast-enhanced CT and DSA in the future. PMID- 8367607 TI - [An unclear circulatory disorder]. PMID- 8367608 TI - Engineering considerations in the development of the automatic implantable cardioverter defibrillator. AB - Each of the authors played a significant role in the design and development of one or more of the Medrad/Intec/Cardiac Pacemakers Inc defibrillators. In so doing, each has contributed to the realization of Dr Mirowski's dream. That tens of thousands of patients have now benefitted from his leadership and that many AICDs will soon be competing in the marketplace is testimony to his truly remarkable vision and persistence. PMID- 8367609 TI - Influence of the implantable cardioverter defibrillator on survival: retrospective studies and prospective trials. PMID- 8367610 TI - Developmental history, early use, and implementation of the Automatic Implantable Cardioverter Defibrillator. PMID- 8367611 TI - The Coronary Artery Bypass Graft (CABG) Patch Trial. The CABG Patch Trial Investigators and Coordinators. PMID- 8367612 TI - Effect of in vitro exposure to acrolein on carbachol responses in rat trachealis muscle. AB - Isolated tracheal rings obtained from male Wistar rats 10 to 15 weeks old and weighing 300 to 400 g were exposed to aqueous solutions of acrolein, and the resulting change of smooth muscle contractility was evaluated by measuring the cumulative carbachol concentration-response curve. Using the product of acrolein concentration and time as a surrogate for the acrolein dose delivered to the smooth muscle cells, contractility measured after a variety of exposure concentrations from 0.01 to 3.0 microM and times from 5 to 60 min could be correlated in a dose-dependent manner. In the range of doses from 0.1 to 6 microM min, relative contractility continuously increased from 0 to 50% above unexposed control values. At doses greater than 6 microM-min, the enhancement in contractility declined. This decline may have been due to cell damage or cell death which was so severe at a dose of 60 microM-min that contractility fell below control values. Below a threshold dose of 0.1 microM-min, acrolein had no effect on contractility. The role arachidonic acid metabolism in the enhancement of smooth muscle reactivity to carbachol was studied using indometacin to block the cyclo-oxygenase pathway and NDGA to block the lipoxygenase pathway. At a concentration of 10 microM of either indometacin or NDGA, the acrolein-induced enhancement in airway reactivity was completely inhibited. At lower concentrations, inhibition by these two chemicals was partially additive, suggesting that both the lipoxygenase and cyclo-oxygenase pathways play a role in the hyperreactive response. PMID- 8367613 TI - Capsaicin-induced reflex bronchoconstriction in the newborn. AB - Although bronchoconstriction in response to C-fibre stimulation has been reported to be weak or absent in the newborn, pulmonary resistance and compliance have not been measured. We tested the hypothesis that capsaicin reflexly activates pulmonary efferent outflow to airway smooth muscle in the newborn. We measured breath-by-breath responses of inspiratory lung resistance (RLi) and dynamic compliance (CLdyn) in 13 newborn dogs and 4 newborn pigs during right heart injections of saline, capsaicin (25-50 micrograms/kg) and acetylcholine (ACh). Repeat capsaicin injections at 5 min intervals were made to test for desensitization in the newborn dog. All newborn dogs and 2 of 4 newborn pigs displayed a brisk bronchoconstriction; in the dog, RLi increased maximally by 97% +/- 13 (SE) and CLdyn decreased maximally by 32% +/- 2. In both species, initial capsaicin injections (CAP1) caused a long latency (time to peak heart rate 26.8 +/- 2 and 20 sec +/- 2.5) increase in heart rate (40% +/- 11 and 20.1% +/- 8.2 for the newborn dog and pig respectively). In the dog, but not the pig, capsaicin responses after the ACh trial (CAP2 and CAP3) caused a short latency bradycardia while the long latency tachycardia continued to be expressed in both species. The maximal changes in RLi and CLdyn, and the bradycardia, were reduced (i.e. desensitized) by 36%, 53% and 63% respectively if capsaicin injection was repeated within 5 min. Muscarinic blockade with atropine abolished the bronchoconstrictor and bradycardia responses to capsaicin but had no effect on the tachycardia. We conclude that the newborn possesses the neural circuitry to mount a bronchoconstrictor response to C-fibre stimulation. We speculate that the response is designed to reduce dead space and stabilize highly compliant airways of the newborn during the rapid shallow breathing that is typically associated with C-fibre stimulation. PMID- 8367614 TI - Reduced voluntary drive to breathe in asthmatic subjects. AB - Maximal voluntary drive to the diaphragm and a non-respiratory muscle group (elbow flexors) was compared in 10 control subjects and 11 asthmatics who were studied when well. The degree of voluntary activation during repeated attempted maximal quasi-static efforts was determined using the twitch interpolation technique in the absence of contractile fatigue under both control conditions and following bronchial challenge with histamine. Diaphragm activation was assessed using bilateral phrenic stimulation at the normal resting end-expiratory lung volume after exhalation from TLC. Asthmatic subjects showed lower and more variable voluntary activation than control subjects for both diaphragm (82.0% +/- 18.4 [SD], vs 87.8% +/- 12.0, P < 0.01) and elbow flexors (91.3% +/- 7.6 vs 95.8% +/- 4.1, P < 0.01). Histamine challenge decreased FEV1 in asthmatic subjects to 50% of the initial value, but had no significant effect on voluntary activation in either subject group. The decreased voluntary drive to the diaphragm observed in some asthmatic subjects may predispose to rapid development of ventilatory failure during severe airway narrowing. PMID- 8367615 TI - The carotid body in the motorneuron response to protriptyline. AB - Protriptyline (PRT) has been shown to preferentially stimulate upper airway inspiratory motorneurons relative to phrenic activity in hyperoxic hypercapnia in the decerebrate cat via a carotid body-independent mechanism. Since previous studies indicated that carotid body stimulation results in preferential activation of upper airway respiratory muscles during both hypercapnia and hypoxemia, we hypothesized that if PRT preferentially stimulated upper airway motorneurons, the mechanism of action might involve the carotid body. We investigated the effect of PRT on carotid body function by comparing the electrical activity of the hypoglossal (HYP) with that of the phrenic (PHR) nerve in carotid sinus nerve intact (CSNI) and CSN-sectioned (CSNX) anesthetized rats, before and after PRT (0.5 mg/kg i.v.), during 100% O2, 15% O2 (N2 balance), and 4% CO2 (O2 balance) administration. The moving time average (MTA) peak inspiratory electroneurogram activities of both the HYP and PHR nerves increased an equivalent amount after PRT injection during hyperoxia, in both CSNI and CSNX rats. During hypoxia, the HYP activity increased significantly more than the PHR activity only in CSNI rats after PRT injection. During hyperoxic hypercapnia, HYP MTAs increased a similar amount in the CSNI and CSNX rats. We conclude that the HYP and PHR respiratory motorneuron pool responses to PRT depend on the blood gas status at the time of drug administration. PMID- 8367616 TI - Stride length and respiratory tidal volume in exercising thoroughbred horses. AB - The purpose of this study was to test the hypothesis that locomotor-respiratory coupling in horses may provide a basis for the appropriate matching of lung ventilation to running speed and metabolic power. This was achieved by determining the effect on respiratory frequency and tidal volume in thoroughbred horses of changing running speed while maintaining a constant metabolic demand by also varying the incline of the treadmill. This procedure was performed at three different speeds at two different levels of metabolic rate. It appears that, in response to metabolic demands which are not directly related to speed, horses can control tidal volume independently of stride length but they do not vary respiratory frequency independently of stride frequency. When running at 0 degrees incline, however, they probably do not operate an elevated tidal volume, because of the increased energetic costs such an elevated tidal volume would incur. PMID- 8367617 TI - Effects of inspiratory support upon breathing in humans during wakefulness and sleep. AB - We have compared the effects on breathing of inspiratory mechanical support during wakefulness and sleep in healthy subjects. Nine awake volunteers breathed through a nose mask connected to a machine supplying variable levels of inspiratory positive airway pressure (IPAP). Tidal volume (VT), breath duration (TTOT) and end-tidal PCO2 (PETCO2) were measured over 1 min steady state periods with IPAP set at a minimal level (approx. 2 cmH2O) and at approx. 10 cmH2O. This protocol was repeated in 6 of the subjects during non-REM sleep. When awake, "10 cmH2O IPAP" caused a significant increase in mean VT from 513 to 842 ml and a significant fall in PETCO2 from 39.7 to 32.7 mmHg. During sleep, "10 cmH2O IPAP" caused no significant changes in VT (388 to 390 ml) or PETCO2 (41.8 to 39.8 mmHg). In each state, "10 cmH2O IPAP" had no significant effect on TTOT. Three subjects repeated the protocol with diaphragmatic surface EMG recorded as an index of efferent inspiratory activity. "10 cmH2O IPAP" had no consistent effect on EMG when awake but caused a reduction in each subject during sleep. We conclude that during non-REM sleep, inspiratory mechanical support is associated with a compensatory decrease in efferent inspiratory activity to achieve a similar tidal volume with maintenance of arterial PCO2. When awake, a "wakefulness drive to breathe" may be associated with maintained inspiratory activity such that mechanical support results in an increased tidal volume despite a fall in arterial PCO2. PMID- 8367618 TI - Intramedullary sodium cyanide injection on respiratory and vasomotor responses in cats. AB - To examine the effect of hypoxia confined to the ventrolateral medulla we microinjected NaCN into the cat medulla (1.0 mm below the ventral surface) unilaterally and investigated cardio-respiratory changes. We studied anesthetized artificially ventilated animals and measured the electrical activity of phrenic and cervical sympathetic nerves and blood pressure. Histotoxic hypoxia depressed phrenic amplitude and elevated sympathetic tone and blood pressure. These responses were obtained predominantly from the region 5.0-8.0 mm caudal to the foramen caecum and 3.0-5.0 mm lateral to the midline (intermediate area). A study with 14C-cyanide showed that total and covalently bound cyanide was confined within a 1 mm diffusion sphere following microinjection. Isolated areas in both rostral and caudal medulla responded to cyanide with elevated sympathetic tone in the absence of phrenic nerve depression, suggesting dissociation of respiratory and vasomotor responses to hypoxia. Thus, the respiratory depression and vasomotor excitation produced by central hypoxia can be reproduced by hypoxia limited to discrete regions of the ventrolateral medulla. PMID- 8367619 TI - Histamine enhances vagal pulmonary C-fiber responses to capsaicin and lung inflation. AB - Effects of histamine on the base-line activity of vagal pulmonary C-fibers and their responses to chemical and mechanical stimulations were studied in anesthetized, open-chest dogs. Histamine aerosols (5 breaths, 1% solution) increased the change in tracheal pressure per breath (delta Pt) to 53 +/- 9% (mean +/- SE) above its base line, whereas an accompanying increase in activity was found in only 27% of the C-fibers studied and hence the overall afferent activity was not significantly different from the control. After Pt returned toward the base line in several minutes, the receptor activity evoked by right atrial injection of capsaicin (0.8-4.0 micrograms/kg) increased from a base line of 0.43 +/- 0.02 imp/sec to 8.12 +/- 1.16 imp/sec (averaged over 10 sec), which was markedly greater and longer lasting than the response triggered by the same dose of capsaicin after phosphate buffer aerosols (4.72 +/- 0.71 imp/sec). Furthermore, pretreatment with histamine aerosols also enhanced the afferent responses of these receptors to static lung inflation (Pt = 20 cmH2O). We conclude that the low dose of histamine aerosols alone did not consistently stimulate the vagal pulmonary C-fibers, but it potentiated the stimulatory effects of both capsaicin and lung inflation on these receptors. PMID- 8367620 TI - Sensory receptors in the first gill arch of rainbow trout. AB - Afferent neural activity was recorded from sensory receptors innervated by the glossopharyngeal nerve (cranial nerve IX) in isolated, perfused first gill arch preparations from rainbow trout. The present study demonstrates the presence of every major type of peripheral cardio-respiratory receptor described in fish in this preparation. Oxygen-sensitive chemoreceptors responsive to internal and/or external hypoxia and cyanide were present. Qualitatively these receptors behaved in an identical fashion which was also similar to that described for mammalian carotid body chemoreceptors. About 5% of the sensory receptors examined were O2 sensitive. proprioceptors were the most numerous receptor type identified and were sensitive to mechanical stimulation of the arch, rakers or filaments. Finally, baroreceptors, the least numerous class of receptor identified, were also present with activity that was altered in response to changes in perfusion pressure. While the reflex responses elicited by the stimulation of these receptors were not addressed in this study, it is likely that these receptors contribute to the reflex cardio-respiratory responses to changes in gill perfusion, gill deflection and hypoxia (environmental or internal) described in fishes. These data thus support suggestions concerning homologies between the first gill arch of teleosts and the carotid bodies of mammals and the importance of the first gill arch in trout in cardio-respiratory control. PMID- 8367621 TI - Carcinosarcomas: current perspectives and an historical review of nosological concepts. AB - The origins of the concepts pertaining to the histogenesis of "carcinosarcomas" (CS) can be traced to theories that were advanced more than 100 years ago. Since that time, debate has continued over the clonality of these neoplasms and their corresponding lineages of differentiation. This article considers the historical aspects of CS and attempts to place these premises in a modern perspective. A review of current ultrastructural, cell-culture, and immunohistological data is used to support a monoclonal nature for carcinosarcoma, and to suggest that "sarcomatoid carcinoma" is a more apt designation for this tumor entity. PMID- 8367622 TI - Sarcomatoid neoplasms of the breast: proposed definitions for biphasic and monophasic sarcomatoid mammary carcinomas. AB - Biphasic sarcomatoid carcinomas (SC) of the breast are defined as tumors that are composed of overtly carcinomatous and sarcoma-like elements and were known in the past as "carcinosarcomas." On the other hand, monophasic SC show features that are similar to those of sarcomas, but epithelial differentiation is detected in the former of these lesions by immunohistochemical methods. Adequate tissue sampling often is required to demonstrate both components of biphasic SC; if properly performed, this procedure greatly reduces the diagnosis of true mammary "sarcoma." The carcinomatous element of biphasic tumors is characterized either by features of a squamous carcinoma or an invasive ductal adenocarcinoma. Squamous differentiation is more often associated with a spindle-cell, fibrosarcoma-like, or malignant fibrous histiocytoma (MFH)-like sarcomatoid component, whereas adenocarcinomas usually are admixed with sarcoma-like tissues having "heterologous" properties. The overtly epithelial elements of biphasic SC are always immunoreactive for keratin, but areas that simulate sarcoma express this protein more heterogeneously. Both components may show positivity for vimentin, although the sarcoma-like elements do so more consistently. Monophasic SC is composed solely of fusiform and pleomorphic cells that are keratin-positive despite their mimicry of sarcomatous differentiation. This tumor variant commonly assumes a myxoid, angiomatoid, or storiform growth pattern, without recognizable carcinomatous foci by light microscopy. Prognosis and involvement of regional lymph nodes in mammary SC cases is controversial, because different tumors have been grouped together in the past for the analysis of these variables. However, SC generally has a less favorable outcome than that of ordinary invasive carcinomas of the breast.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367623 TI - Sarcomatoid neoplasms of the respiratory tract. AB - Sarcomatoid carcinomas (SCAs) of the respiratory tract are uncommon neoplasms of adults, most of whom are men in late middle-age who have a long history of tobacco usage. These tumors may be observed in the paranasal sinuses, nose, naso oropharynx, larynx, trachea, central bronchi, or peripheral lung parenchyma. They may assume a polypoid configuration, with projection into luminal spaces, or show an infiltrative growth pattern like that of typical high-grade carcinoma. Histologically, both biphasic and monophasic variants of SCAs are recognized. The former include tumors with foci of overt carcinoma admixed with areas of divergent differentiation into "committed" mesenchymal tissues, such lesions have usually been termed "carcinosarcomas" in the past. On the other hand, monophasic SCAs lack obviously epithelial foci on light microscopy. Ultrastructural and immunohistological studies support the notion that SCA represents a continuum that embraces carcinosarcomas and spindle-cell carcinomas, all of which are basically epithelial neoplasms. Tumor behavior is site-dependent; SCAs of the nose, sinuses, pharynx, and lungs usually pursue an aggressive course, whereas histologically similar lesions in the larynx are usually found at an earlier stage and, therefore, are associated with a better prognosis. PMID- 8367624 TI - Anaplastic (sarcomatoid) carcinoma of the thyroid gland. AB - Anaplastic (sarcomatoid) carcinomas of the thyroid gland (ACT) seem to be decreasing in frequency. During the past 45 years, a threefold to fourfold diminution in the number of ACT cases has been seen internationally. Despite this fact, these tumors continue to pursue a lethal course in virtually all cases. Clinically, ACT are characterized by rapidly growing neck masses, often in patients who have had long-standing thyroid nodules or goiters. Microscopically, ACT shows a mixture of fusiform and pleomorphic tumor cells, with widespread permeation of surrounding cervical tissues. Osteoclast-like giant cells, intranuclear cytoplasmic invaginations, and divergent differentiation into chondro-osseous, vascular, or myogenic tissues also may be observed in ACT histologically. The common presence of admixed foci of differentiated thyroid cancer in ACT suggests that the latter neoplasm arises through the mechanism of "clonal evolution." Keratin is observed immunohistologically in roughly 80% of cases, further supporting this contention. Because the incidence of ACT has inversely paralleled increasing use of thyroid surgery in general, it may be hypothesized that early removal of hyperplastic or neoplastic thyroid tissue aborts the previously mentioned "dedifferentiation" phenomenon. PMID- 8367625 TI - Sarcomatoid carcinomas (carcinosarcomas) of the gastrointestinal tract: a review. AB - This review discusses sarcomatoid carcinomas of the gastrointestinal tract, rare malignant neoplasms that demonstrate both epithelial and mesenchymal differentiation. The clinical, histological, immunohistochemical, and ultrastructural features are described. Practical problems in the differential diagnosis of these tumors are also discussed. PMID- 8367626 TI - Sarcomatoid lesions of the urogenital tract. AB - Spindle-cell lesions other than sarcomas are relatively rare occurrences along the urogenital tract but include both benign and malignant processes. Inflammatory pseudotumors may occur anywhere along the urothelial tract; they may follow a surgical procedure or appear de novo. Malignant tumors may be classified as sarcomatoid carcinomas or carcinosarcomas according to their degree of differentiation, the latter containing obvious mesenchymal components. Generally both arise in a background of high-grade carcinoma and are of a high pathological stage at the time of initial presentation. For this reason they have a poor prognosis. Because the deferential diagnosis of spindle-cell neoplasms include both benign and malignant lesions, great care must be taken in making the correct diagnosis. PMID- 8367627 TI - Unwritten knowledge in nursing: consider the spoken as well as the written word. AB - Knowledge has been defined as familiarity gained by experience or a person's range of information and theoretical understanding (Sykes, 1982). The distinction is made to avoid confusion with the knowledge of scientism (Bullock, Stallybrass, & Trombley, 1988), where true or factual knowledge is held to be derivable only from the inductive methods of the natural sciences. Knowledge has its origins in a broader field of understanding than that of empirical measurement. PMID- 8367629 TI - The common sense model: an organizing framework for knowledge development in nursing. AB - The common sense model emphasizes the importance of persons' perceptions or beliefs about their health and illness, and has potential for guiding knowledge development in nursing. This paper describes the model, reviews the existing relevant literature, and organizes the literature within the framework of the model. Suggestions are made as to how the model can be used for further research in nursing. PMID- 8367628 TI - Patient advocacy--an important part of the daily work of the expert nurse. AB - Over the past two decades, patient advocacy has been recognized as a part of nursing. For the most part, the issue has been treated by means of theoretical reasoning and case studies. Narratives describing lived experiences of nursing by expert nurses from Sweden were analyzed in this study. The nurses were identified by their superiors as expert nurses, as having a special gift, a "green thumb" for nursing. One third of the narratives concerned patient advocacy situations. The analysis of the narratives showed that the patient advocacy situation is composed of the following elements: a powerless patient, a problem concerning the patient's own will or what is good for him or her, and an adversary. Further, it includes a trigger situation, and a prompt decision and action by the nurse. The nurse acts out of conviction, accepts an additional work load, and takes the risk of being punished. PMID- 8367630 TI - Development and validation of the Perinatal Nursing Self-Efficacy Scale. AB - Self-efficacy, a central construct of Bandura's social cognitive theory, provided the framework for developing a measure of perinatal nursing knowledge and skills. The 24-item Perinatal Nursing Self-efficacy Scale (PNSE) encompasses knowledge and skills required of nurses practicing in family-centered single room maternity care (SRMC) settings. Response data from 188 registered nurses were evaluated to assess the reliability and construct validity of the instrument. The instrument demonstrated strong factorial validity and subscales derived from the factor analysis generated high alpha reliabilities. A MANOVA produced results consistent with the propositions of self-efficacy theory and supported construct validity. Since self-efficacy expectations are situation specific and have significant predictive value, they provide both an important adjunct to needs assessment data for educational planning and helpful baseline data for outcome evaluation of perinatal nursing educational programs and transitions to SRMC settings. PMID- 8367631 TI - [Pelvic endoscopic lymphadenectomy in the assessment of early cancer of the uterine neck: survey of 25 French hospital centers]. AB - Accurate staging of invasive cervical cancer is essential to its adequate treatment. Current clinical staging of cervical cancer is inaccurate, particularly for lymph-nodes evaluation. At reduced cost and risks laparoscopic pelvic lymphadenectomy allows accurate detection of lymph-node metastases. Its place in the staging of early cervical cancer is being evaluated. Our inquiry, multicentric and including more than 500 laparoscopic pelvic lymphadenectomies, leads to the conclusion that this technique is accurate and is associated with a reduced but variable morbidity depending on the technique and operator's ability. The implications of the results of laparoscopic lymphadenectomy in the type and modalities of subsequent treatment are discussed. PMID- 8367632 TI - [Principles of 3-pronged therapy of juvenile diabetes: insulin, diet, sports]. PMID- 8367633 TI - [Treatment of rheumatoid arthritis: current and future]. AB - Rheumatoid arthritis (RA) is a chronic articular inflammatory disease of unknown aetiology. The therapeutic approach can be achieved at different levels: 1) symptomatic treatment with nonsteroidal anti-inflammatory drugs which can relieve articular pain and stiffness, 2) second-line drugs (or DMARD, for Disease Modifying Anti-Rheumatic Drug) selected for their capacity to slow the rheumatoid process. During this last decade, sulfasalazine and methotrexate became an alternative choice to the "classical" slow-acting antirheumatic drugs such as gold, D-penicillamine or antimalarials. The extensive progress in basic immunology and especially in the immunopathology of RA has allowed the elaboration of a new approach to immunotherapy, aimed at molecular targets on cells from the "specific immunity" system or against mediators of the inflammatory process, such as the cytokines. PMID- 8367634 TI - [Fulminant hepatic failure of neoplastic origin]. AB - The case of a 59-year-old woman, hospitalised for a degradation of her health status which evolved within 10 days in fatal liver failure is reported. Although acute yellow atrophy was diagnosed, its origin remained elusive. Post-mortem examination of the liver disclosed massive hepatic infiltration by a breast adenocarcinoma. The causes of acute hepatic failure are reviewed and, particularly, the neoplastic ones. PMID- 8367635 TI - [Mineral density measurement of the lumbar spine: expression of results]. AB - The many ways of presenting measurements of bone mineral density of the lumbar spine are illustrated in the case of a 65-year-old osteoporotic female. It is preferred to express the actual measurement relative to the mean density value observed in a group of 30-45 year old normal premenopausal women, in T-score or in percentage of expected normal value. PMID- 8367636 TI - [Directional coronary atherectomy. Local experience]. PMID- 8367637 TI - [Venous ulcer: etiopathogenesis and treatment]. PMID- 8367638 TI - [Ophthalmological treatment of Lyell's syndrome]. PMID- 8367639 TI - [Diagnosis of skin infections caused by simplex-type herpes virus and by varicella zona]. PMID- 8367640 TI - [Disinfection and sterilization: an overview for clinical practice]. AB - The importance of disinfection and sterilization has increased in the past decade with the spread of HIV and Hepatitis B and C virus. Clear written instructions for sterilization and disinfection must be provided for all relevant items. The principles of sterilization and disinfection are reviewed with emphasis on clinical practice. Important examples and frequent clinical problems are discussed in detail by using the disinfection guidelines of the University Hospital of Basel. PMID- 8367641 TI - [Body fat distribution: independent factor affecting the blood lipid profile]. AB - The association of life style factors with profiles of blood lipids is described in a cohort of 75 middle aged (41.2 +/- 7.8 years) physically inactive, nonsmoking employees. The importance of body fat distribution in relation to relative body weight and the lipid profiles was also studied. The strongest possible predictor for an atherogenic lipid fraction was the quotient of abdominal and hip circumferences indicating an abdominal fat accumulation. In the group with the lowest quotient (< 0.84) the triglyceride and cholesterol values were lower by 43% and 13% respectively than in that with the highest quotient (< 0.88). The body mass index (BMI) gave the best inverse correlation with HDL-c and Apo A-I: Men with a BMI < 23.7 kg/m2 had in the average a HDL-c concentration 0.2 mmol/l higher than slightly overweighted men (BMI > 25 kg/m2). Physical inactivity and a reduced physical endurance were both associated with significantly higher total cholesterol and Apo B values. In a multivariate analysis the quotient of abdominal and hip circumferences, physical activity and endurance together with adherence to recommended nutritional behaviour explained approximately one third of the variations in LDL and Apo-B concentrations. This study thus confirms in a cohort of non smoking middle aged employees the predictive character of unfavorable life style for an atherogenic lipid profile. The assessment of body fat distribution added further information on the lipid profile that could not be detected by body size and weight determination alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367642 TI - [The pitfalls of cruralgia]. AB - Crural neuralgia can initially present as an involvement of the hip joint. We studied some clinical factors helpful for the diagnosis, which is sometimes difficult. PMID- 8367643 TI - [Respiratory insufficiency and kidney failure 2 months following kidney transplantation]. PMID- 8367644 TI - [A case from practice (273). Femur head necrosis]. PMID- 8367645 TI - [Nutrition problems in ambulatory geriatrics]. PMID- 8367646 TI - [The role of retrograde cholangiography in the diagnosis and treatment of common bile duct calculi]. PMID- 8367647 TI - [Manometry of the small intestine: technical progress and limitations]. PMID- 8367648 TI - [Mutants of the hepatitis B virus: description and value for a better understanding of this disease]. PMID- 8367649 TI - [Acute diverticulitis of the left colon: diagnostic and therapeutic approach]. PMID- 8367650 TI - [Clinical aspects and complications of puncture biopsy of the liver: results of a Swiss study and review of the literature]. PMID- 8367651 TI - [Retrosternal pain. Clinical conference about a subject with esophagitis]. PMID- 8367652 TI - [Do we think of celiac disease frequently enough?]. PMID- 8367653 TI - [Acute urinary retention as a manifestation of a myeloradiculitis]. PMID- 8367654 TI - [What do they know about nutritional equilibrium?]. PMID- 8367655 TI - [Jaques-Louis Reverdin (1842-1929) and his cousin Auguste (1848-1908) or when clinical surgery precedes experimental physiology]. PMID- 8367656 TI - Evaluation of the in vitro transformation technique to distinguish Trypanosoma evansi from cyclically transmitted Trypanozoon stocks. AB - In order to initiate transformation into procyclic forms, bloodstream trypanosomes, were transferred to semi-defined medium at 27 degrees C. All stocks previously classified as Trypanosoma brucei rhodesiense, T.b. gambiense and T.b. brucei transformed into procyclic forms. None of the 31 characterized T. evansi stocks transformed into procyclic forms, but died between day 4 and day 6 in culture. On the other hand, 3 out of 64 stocks of monomorphic brucei subgroup field isolates from camels transformed into procyclic forms, confirming the existence of T.b. brucei infection in camels kept close to tsetse belts. PMID- 8367657 TI - Evolution of chloroquine resistance in central and west Africa. AB - The evolution of in vitro chloroquine susceptibility of clinical isolates of Plasmodium falciparum obtained from travellers returning to France was studied between 1986 and 1991 using the isotopic semi-microtest. Based on the analysis of 1,147 interpretable tests on isolates originating from Central and West Africa, the study showed that the proportion of chloroquine-resistant falciparum malaria remained stable between 1986 and 1988 and has diminished between 1989 and 1991. The diminution of chloroquine-resistant imported malaria may be associated, at least in part, with a better compliance of French travellers with the recommendation to use either mefloquine or a combination of chloroquine and proguanil since 1989 and an increasing proportion of African immigrants who tend to neglect regular chemoprophylaxis during the visit to their countries. The reason for the stabilisation of chloroquine resistance is unknown, and this phenomenon may be temporary, necessitating a continuous surveillance of drug susceptibility. PMID- 8367658 TI - Characterization of a variant tandem repeat from Sudanese Onchocerca volvulus. AB - Strategies for detection and control of onchocerciasis in Africa have included identification of DNA probes and PCR target sequences for sensitive and specific detection of parasites. To evaluate the applicability of published PCR and DNA probe based methods for the study of onchocerciasis in Sudan, we collected adult O. volvulus from geographically distinct regions of Sudan (700 miles apart), Abu Hamed (northern desert) and Raja (southwestern savannah), and we examined the similarities between Sudanese O. volvulus repeats and published versions of the repeat from West African O. volvulus. Amplification of DNA extracted from the Raja O. volvulus strain predictably generated a ladder of products, multiples of the base 150 bp repeat, as has been reported from West Africa. However, amplification of DNA from the Abu Hamed O. volvulus isolate resulted in a series of doublets. The unexpected DNA fragments thus amplified differed in size from the base 150 bp unit by approximately 50 base pairs and was most clearly visualized at 150-200 base pairs. DNA sequence analysis of the amplified repeats in the isolate of O. volvulus from Abu Hamed revealed a variant of the 150 bp tandem repeat which contained an extra 49 bp. The additional 49 bp contained two short repeats of 21 bp and 10 bp, corresponding to bases 99-119 and 128-137 respectively, of the known 150 bp O. volvulus repeat. This work demonstrates a variant of the O. volvulus 150 bp tandem repeat, which easily distinguishes Raja and Abu Hamed isolates of O. volvulus, and which has potential value for differentiating Abu Hamed strains of O. volvulus from other strains in East Africa. PMID- 8367659 TI - Analysis of the genomic sequence encoding the 29-kDa cysteine-rich protein of Entamoeba histolytica. AB - By analyzing cDNA and genomic clones coding for the 29-kDa cysteine-rich protein of Entamoeba histolytica, substantial sequence differences were found to the 5' end of a previously described full-length cDNA coding for the same protein (Reed et al., 1992), which was reported to contain an untranslated 5'-sequence of at least 171 nucleotides, unusual for E. histolytica cDNAs. We found evidence that the cDNA published by Reed et al. (1992) represents a hybridclone composed of two unrelated sequences and that the gene coding for the 29-kDa molecule comprises all of the features typical for E. histolytica genes. A data base analysis revealed substantial sequence homology of the 29-kDa protein to a class of polypeptides found in prokaryotic organisms that may be involved in the inactivation of hydrogen peroxide. PMID- 8367660 TI - Second conference of the International Ethical Committee on AIDS. Introduction into the theme. PMID- 8367661 TI - AIDS in Asia. PMID- 8367662 TI - AIDS in Africa--the Ugandan experience. The AIDS Support Organization. PMID- 8367663 TI - AIDS: epidemiology and the international response. PMID- 8367664 TI - Special problems in the "Third World" possibilities of intervention concerning prevention and care of AIDS in the "Third World". PMID- 8367665 TI - Social and economic aspects of AIDS, the implications of AIDS and the resulting priorities in the field of development cooperation. PMID- 8367666 TI - 2nd conference of the International Ethical committee on AIDS--Resolution. PMID- 8367667 TI - The population dynamics of Onchocerca volvulus in the human host. AB - The quantitative aspects of onchocerciasis that focus on the relationship between the number of adult female Onchocerca volvulus in the human host, the total numbers of microfilariae (mfs) in the body at any one time, and the numbers of infective larvae (L3) to which a person is exposed over time, have received little attention. This paper attempts to investigate the problem from three starting points:--(a) using the numbers of palpable nodules to estimate the numbers of productive female worms in the body; (b) using the concentrations of mfs in skin snips to estimate the total load of mfs in the body; and (c) using the Annual Transmission Potential to estimate the numbers of L3 developing to productive female maturity. By analysing published and unpublished data relating to the forest and savanna zones of West Africa, these three approaches indicate that a relatively large proportion of adult female worms lie deep in the body and are impalpable from the surface. They also provide numerical results, of the same order to magnitude, which can be linked to provide estimates of the total numbers of adult female worms and mfs in the bodies of persons with infections of different intensities. PMID- 8367669 TI - Wuchereria bancrofti: identification of parasitic acetylcholinesterase in microfilariae infected human serum. AB - An antigen with cholinesterase activity was detected in the sera of patients infected with Wuchereria bancrofti. The asymptomatic microfilaremic sera showed 3 to 4 times more cholinesterase activity for acetylthiocholine (ATCh) as compared to sera of symptomatic amicrofilaremic, hookworm infected and endemic normals, whereas the activities for butyrylthiocholine (BTCh) did not significantly differ. The enzyme activities from both sources, namely from sera of microfilaremic cases and from endemic normals, were partially purified and according to substrate specificity for ATCh and BTCh as well as inhibition of the former activity by excess substrate classified as acetylcholinesterase (AChE; EC 3.1.1.7) and pseudocholinesterase (AChE; EC 3.1.1.8), respectively. The Km-value for ATCh of the cholinesterase from the microfilaremic sera was determined to be 0.87 mM. Eserine competitively inhibited the AChE activity; the inhibition constant was found to be 1.3 microM. The BChE from the normal sera had Km-values of 0.15 and 0.20 mM for BTCh and ATCh, respectively, and did not show significant inhibition by eserine. These and other dissimilarities suggest a difference in nature of the cholinesterases in microfilaremic and normal sera and propose that the former enzyme, a true acetylcholinesterase, originates from the parasite. Additional evidence for the origin of the AChE-activity from the parasite was provided by ELISA-studies; anti-Brugia malayi AChE antibodies confirmed antigenecity and cross reactivity of the AChE in infected sera, whereas the antibodies did not show any cross reactivity with the BChE in normal sera. PMID- 8367668 TI - Epidemiological studies of onchocerciasis in southern Benin. AB - We studied the prevalence of human onchocerciasis in four geographically different regions of the southern part of Benin in West Africa. In a total of thirteen villages 1596 individuals were examined for clinical and parasitological signs of onchocerciasis. Prevalence of microfilariae of Onchocerca volvulus in skin snips was 29% in region I (lower Oueme river), 64% in region II (Mono river), 56% in region III (upper Oueme river) and 70% in region IV (Okpara river). Based on endemicity criteria of the WHO regions II and IV were found to be hyperendemic, region III mesoendemic and region I hypoendemic for onchocerciasis. The community microfilarial load ranged from 4 mf/mg skin in the hypoendemic region to 10.5 mf/mg skin in the hyperendemic regions. The prevalence of nodules was 21% in region I, 30% in region II, 17% in region III and 41% in region IV. The overall prevalence of chronic onchocercal dermatitis was 12%. Of 689 individuals infected with O. volvulus 388 were treated with a single dose of ivermectin. PMID- 8367670 TI - Safety trial of single-dose treatments with a combination of ivermectin and diethylcarbamazine in bancroftian filariasis. AB - A supervised safety trial of the treatment with a combination of ivermectin 400 micrograms.kg-1 (IVER 400) plus increasing doses of diethylcarbamazine (DEC), given simultaneously in single dose, was performed on five groups of Polynesian Wuchereria bancrofti carriers, 49 males aged 25 to 73 years, in whom microfilaremia ranged from 1 to 6,137 mf/ml. The trial was hospital-based, open, dose-escalating (1 group per week). Safety of an unchanging dose of IVER 400 and ascending doses of DEC were studied in the 5 following groups: group 1- IVER 400 plus DEC 1 mg.kg-1, 12 patients; group 2- IVER 400 plus DEC 3 mg.kg-1, 17 patients; group 3- IVER 400 plus DEC 6 mg.kg-1, 10 patients. Two control groups were included in the study, group 4- DEC 6 mg.kg-1 alone, 5 patients; group 5-: IVER 400 alone, 5 patients. Carriers were examined and questioned regarding their experience of adverse reactions, which were graded 0 to 3 according to severity, at 6, 12 and 24 hours and at 4 days after treatment. Biological examination was performed 4 days before and 4 days after treatment and included determination of microfilaremia, complete blood count, liver function tests and assessment of creatinine and urea levels. Adverse reactions were observed in 51% of 49 carriers (15 of grade 1, 8 of grade 2, 2 of grade 3). None was considered serious and they all disappeared in 2 days. The main symptoms were fever > or = 37.5 degrees C, myalgia, arthralgia, headache, asthenia, anorexia, vertigo and chills. Adverse reactions of patients were not significantly different between the five groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367671 TI - Periodicity of Wuchereria bancrofti var. pacifica filariasis in French Polynesia. AB - In 1992, a study on microfilaremia periodicity was carried out on 12 Wuchereria bancrofti carriers in the Marquesas islands. Blood samples were collected simultaneously every 4 hours during a 48 hour period by finger-prick and venipuncture for determination of microfilaremia by both blood film and membrane filtration technique methods, and for determination of antigenemia. The membrane filtration results showed no significant nycthemeral variations between the microfilaria densities at hours 16:00, 20:00, 24:00, 04:00, 08:00 and 12:00. Conversely, the blood film method showed a significant difference between the microfilaria densities: the microfilaremia was higher during the day (12:00-20:00 hours) than during the night (24:00-08:00 hours). As for antigenemia, using Og 4 C3 monoclonal antibody, there was no significant fluctuation during 48 hours. These results confirm that W. bancrofti var. pacifica is subperiodic and diurnal in French Polynesia. In particular, they substantiate the validity of examining venous blood by the membrane filtration technique as the judgment criterion of choice in therapeutic trials and of examining capillary blood during peak hours by the blood film method for evaluating the endemic level in a population. PMID- 8367672 TI - Immune response against Trypanosoma cruzi antigens in Cebus apella monkeys. AB - The american primate Cebus apella has been used as an experimental model for the study of acute and chronic Chagas' disease. The antibody response elicited by 4 x 10(6) blood trypnomastigotes injected into four monkeys was analysed. Peak titres of IgM and IgG of anti-Trypanosoma cruzi antibodies were found at day 22, and between days 20 and 40 post-infection (p.i.), respectively. The ability of a Mr 37kDa (T37K) glycoprotein purified from T. cruzi epimastigotes to generate IgG anti-T. cruzi antibodies in monkeys, and protect them against a challenge with trypomastigotes, was also studied. Monkeys non-immunized with T37K reached peak values of parasitaemia between days 18 and 21 post-infection, whereas immunized monkeys had lower parasitaemias without important variation. Anti-T37K antibodies in immunized monkeys decreased from day 2 with the lowest titres between days 14 to 22 p.i., coincident with the peak of parasitaemia in control non-immunized monkeys. These results suggest that anti-T37K antibodies could be responsible for the low parasitaemia detected in immunized monkeys. PMID- 8367673 TI - Trypanocidal activity and platinum plasma kinetics of cis-Pt pentamidine iodide in Trypanosoma brucei sheep model. AB - The trypanocidal properties of cis-Pt pentamidine iodide have been studied on the T. b. brucei sheep model. The compound was evaluated on the lymphatic-plasma phase of the disease and appeared to be active on the circulating parasites. Cis Pt pentamidine iodide was active at 5 mgl.kg-1 in one single dose both in mouse and sheep trypanosomiasis models. The chemotherapeutic index was about 200 in the mouse. As we observed previously with the chloride derivative, platinum plasma values for cis-Pt pentamidine iodide were rather constant between 24 and 48 hours. The nature of the salt associated to cis-Pt pentamidine had a direct effect on the compound kinetics. The iodide compound was distributed quickly and largely within deep compartments according to a monocompartmental model. The theoretical volume of distribution was 6.41.kg-1 for a 100% absorbed fraction. The two iodide ions of the complex probably played an important role in the compound kinetics mainly due to the extended release effect. The iodide salt of cis-Pt pentamidine could therefore be used in chemoprophylaxis of African trypanosomiasis. PMID- 8367674 TI - Pathogenesis and pathology of African trypanosomosis in Baoule, N'Dama/Baoule cross bred and Zebu cattle in Burkina Faso. 1. Clinical performance under high natural tsetse challenge. AB - The pathogenesis and pathology of African animal trypanosomosis (AAT) in Baoule, N'Dama/Baoule-cross-bred and Zebu cattle was studied from 1987 to 1991 in a series of experiments conducted under natural and artificial conditions of challenge at the Centre de Recherches sur les Trypanosomoses Animales (CRTA) in Burkina Faso. This first paper reports on the clinical performance of 64 Baoule, 10 N'Dama/Baoule-cross-bred and 20 Zebu cattle, which were transferred to the pastoral zone of Satiri, 50 km northeast of Bobo-Dioulasso, a zone infested with Glossina palpalis gambiensis, G. morsitans submorsitans and G. tachinoides. Prior to the experiment, the cattle had been raised in a fly proof stable and at the CRTA breeding station, an area of extremely low incidence of trypanosomosis or had been exposed at least once to natural trypanosome challenge in an area of high Glossina density. The cattle were monitored daily for clinical performance. Blood samples were collected twice weekly and examined on the spot for packed red cell volume (PCV) and parasitaemia. In the blood of 98% of the cattle trypanosomes (Trypanosoma vivax, T. congolense) were detected. Significant inter- and intrabreed differences with respect to the clinical performance were recorded. Regarding general health, the humpless Baoule and N'Dama/Baoule cross bred cattle (Bos taurus) proved to be superior to the humped Zebu cattle (B. indicus) under this high challenge. Previous exposure to natural challenge had a positive effect on survival for both Baoule and Zebu cattle. The phenotypic variation in response to trypanosomosis was small in Baoule previously exposed and large in Baoule previously not exposed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367675 TI - Measurement of problem-oriented need for the primary health care services: need for exercise counseling as an example. AB - Based on several previous approaches, a new model for the measurement of needs for primary health care services is constructed and demonstrated. This fourfold model includes the concepts of diagnostic need, perceived need, client dependent demand and provider dependent demand. The empirical results concerning the need for exercise counseling in the primary health care indicated that the present approach is feasible and comprehensive enough to obtain valuable information about the health needs and how they are supplied. The model makes it possible to identify discrepancies, for example, between the experts' and clients' priority ratings and between the criterion-based prevalence of a problem and the practice of the care providers. It may also reveal barriers and inequalities in the use of services. For health administrators and decisionmakers the present problem oriented model provides a systematic approach to assess needs for health care services and to develop the services provided. PMID- 8367676 TI - Fibromyalgia--a new cause for disability pension. AB - Fibromyalgia is a condition under dispute. Accepted by some as a major step forward in understanding some of the patients with widespread muscular pain, looked upon as a confusing side step by others. In 1988 fibromyalgia was by far the most frequent single diagnosis as a reason for disability pension in Norway. Disability statistics however show big differences between counties. Two neighbouring counties had among the lowest and the highest incidence of disability pensioners with the diagnosis fibromyalgia. New pensioners with fibromyalgia and some closely related diagnoses have been studied during the year 1988 by means of reading the insurance records. It became apparent that the difference between the two counties with respect to the incidence of fibromyalgia as a cause of disability pension could be explained by differences in diagnostic setting by the doctors and difference in the assessment from the insurance system, rather than real differences in morbidity pattern. Complaints from the musculoskeletal system is frequent and increasing in the population both as a reason for sick leave and disability pension. Whether this complicated and challenging situation is made more easy to handle by defining a subgroup of those persons as having "fibromyalgia" is questioned. PMID- 8367677 TI - Incontinence pads--prevalence of use and individual consumption. AB - The purpose was to describe the prevalence of incontinence pad use and individual consumption of pads. Data was collected at local Insurance Offices in a region of western Norway (population: 239,500). Overall prevalence was 1.6% for females and 0.4% for males, increasing sharply with age. Median daily consumption was 1.7 pads. Middle-aged persons (40-69 years) consumed fewer and smaller pads than the others. PMID- 8367678 TI - Physiological effects on patients following temporary closing of a geriatric day care unit. AB - Geriatric day care is an essential part of modern geriatric care providing rehabilitation and social support. During a 5 week summer closure of a geriatric day care unit, 24 long attenders (defined as patients having day care > 26 weeks), were non-electively discharged and included in this study. Blood samples were drawn one week before the closure (0 week), at the reopening (7 weeks) and 7 weeks after the reopening (14 weeks). The results show a longitudinal tendency of rising plasma prolactin levels during the whole study period. There was non significant increase in cortisol during the closure followed by a significant decrease 7 weeks after the reopening. All other measures were unaffected. The study indicates that geriatric patients submitted to longterm day care have a measurable psychophysiological response as a result of a non-controllable closure of a day care unit. The changes in plasma prolactin and cortisol levels are part of a general adaptation pattern. The study shows that elderly have a functional physiological response and chronically sick patients react selectively with regard to the hormone response. Thus, the results indicate that the support during minor life events induced by the closure of the day care ward should be improved. PMID- 8367679 TI - Abuse and neglect of the elderly--a Nordic perspective report from a Nordic research project. AB - This article describes how abuse and neglect of the elderly was made an issue for research in a Nordic perspective. The Council of Nordic Ministers funded a cooperation between Nordic researchers on the issue of abuse of the elderly, based on a Norwegian initiative in 1988. The aim was to establish a base of knowledge in order to recommend social and political measures for each country. The researchers were chosen from the disciplines of social work, social anthropology, sociology, nursing sciences and medicine. Interested researchers were hard to find in Iceland and Denmark. Important results are on a theoretical level the discussion and perspectives on the definition of "family", "violence" and "elderly". On the practical level the results reveal that between 8% and 17% of a random population sample in Denmark, Sweden and Finland knew about elderly people being abused in their homes. Between 1 and 8% of elderly people living in their homes are being abused by their close kin, according to either the old people themselves or as reported by home nurses. In one of the Swedish projects 12% of close family members, being responsible for the care of a demented, mostly spouse or parent, admitted abuse towards the demented person. Swedish home nurses described the difficulties in intervening into the abusive families. PMID- 8367680 TI - Accident prevention activities in the Norwegian municipalities: the local response to a nationwide campaign. AB - The Norwegian "Campaign Against Home Accidents" was launched nationwide during 1988 to 1991, with the goal of reducing the incidence of home accidents by 20%. The aim of the campaign was to urge primarily the municipal health services to form local accident prevention groups and to implement local measures for prevention of home accidents. On the basis of two surveys, after one year and at the end of the national campaign, an evaluation was carried out concerning the participation of the municipal health services in the campaign and the impact of the campaign on local accident prevention activities. The results indicate that the national campaign engaged the majority of the municipalities and stimulated local accident prevention work to some extent. Most local activities were health education measures, whereas environmental intervention were less commonly reported. Involvement in the campaign was the variable most related to level of accident prevention activities at the end of the campaign period. However, the relationship was only modest. Restricted economical resources, too little emphasis on environmental change, lack of political involvement and insufficient use of coalition partners at the community level are suggested as the major explanations for the limited effect of the campaign. PMID- 8367681 TI - Dietary knowledge and behaviour among schoolchildren in Copenhagen, Denmark. AB - In 1989, 674 schoolchildren aged 12-14 years in nine elementary schools in a municipality in Copenhagen, Denmark, answered a questionnaire about their dietary habits and knowledge. The majority of the pupils had fruit (87%), vegetables (72%), rye bread (81%), and drank fat-reduced milk (73%) every day. A diet score (reliability = 0.58) was calculated on the basis of the intake of 8 food items relevant to current dietary recommendations. There were no age and sex differences as to dietary habits, but immigrant children had a lower diet score than native children. Dietary knowledge was measured by the ability to state correctly whether 11 different food items had a high content or not of fat, sugar or dietary fibres. Dietary knowledge was highest for questions about fat and sugar. A knowledge score measured the number of correct answers to all 33 questions (reliability = 0.90). Knowledge was highest among older children, native children, and children with the most healthy dietary habits. In the multivariate regression analysis, knowledge, health attitudes and ethnicity were the only significant predictors of dietary behaviour. It is concluded that both social and personal factors are important for dietary behaviour, and health promotion in children should include other methods than educational programmes. PMID- 8367682 TI - Physiological effects on patients following temporary closing of a geriatric day care unit. PMID- 8367683 TI - The meanings of social medicine and public health. AB - The term "social medicine" has been marked by a great deal of confusion in the medical literature, in medical education, and in discussion of systems of health care. It has occupied diverse relationships to the term "public health", which this article will explore. PMID- 8367684 TI - Nordic registers of visually impaired children. AB - A Nordic study group, NORDSYN, consisting of ophthalmologists from Denmark (Thomas Rosenberg), Finland (Sirkka-Liisa Rudanko), Iceland (Gudmundur Viggosson), Norway (Tor Flage, Egill Hansen, Ruth Riise) and Sweden (Kristina Tornqvist), has compiled data from registers in Denmark, Finland, Iceland and Norway of 2527 visually impaired children. The Swedish register was established later in 1990. Each record contains the following information: sex, year of birth, year of registration, classification of visual impairment, ocular diagnosis, systemic diagnosis, aetiology and evt. additional impairments. The ocular diagnoses were compiled into groups among which congenital malformations and neuro-ophthalmological diseases were the most dominating. A coding system for aetiology was developed. It was demonstrated, that prenatal factors, including genetic aetiologies, were involved in a large proportion (66%) of the cases. The sex distribution revealed a dominance of males compared to the general population at the same age. The age-specific national prevalences for registration of childhood blindness (WHO-definition: best corrected visual acuity in the best eye less than 3/60 or visual field less than 10 degrees around fixation for the ages 0-15 years) were (N/100,000): Denmark 41, Finland 15, Iceland 19 and Norway 15. The differences were primarily presumed to be due to varying efficiency in registration. A coding system for additional impairments was developed. The proportion of visually impaired children with an additional mobility, hearing or mental impairment was between one third and one half of the national materials thus indicating the need for interdisciplinary tracing of and care for the visually impaired child. PMID- 8367685 TI - Methods for the evaluation of social effects on birth weight-- experiences with Swedish population registries. AB - All births in Sweden in 1986, registered in the Medical Birth Registry, were analyzed with linked data from the November 1985 census in order to identify variables which could be used as proxy variables for the socio-economic situation of the women, using birth weight as outcome variable. Two phenomena appear to be strong socio-economic indices of significance for birth weight: whether the woman co-habited or not at the census and whether she had a long education (> 14 years) and an "academic" work. The two variables interacted, however: when the woman had a long education, cohabitation status played no significant role. Maternal education as judged from occupation seemed to play a more important role than paternal education or job. To some extent, the effects of the socio-economic variables could be explained by different smoking habits but a residual effect existed which may have different explanations. Cohabitation status and education may be used as estimates of socio-economic level of significance for birth weight and perhaps other pregnancy outcome in the analysis of, for instance, the effect of various occupational exposures on pregnancy outcome. PMID- 8367686 TI - Socioeconomic differences in smoking in an urban Swedish population. The bias introduced by non-participation in a mailed questionnaire. AB - Stockholm Health of the Population Study is a cross-sectional study carried out from 1984-85. Postal questionnaires, telephone interviews and health interviews were used to get information from a sample of 5,199 persons, 18-64 years of age, on health status, risk exposures, healthcare consumption and social factors. Non participation with respect to the postal questionnaire was 36.8%. With subsequent telephone interviews and an invitation to a health interview, non-participation was reduced to 17.8%. The estimated prevalence of daily smoking increased from 36.1% to 38.7. The non-responders had a higher prevalence of daily smoking in all sub-groups. This effect of the efforts to reduce non-participation differed socially. The prevalence of smoking for men, 40-64 years of age, who were reached by telephone was 60.3%. Male professionals and intermediate non-manual workers, 40-64 years of age reached by telephone had a prevalence of smoking, which was twice as high as for the responders of the questionnaire (62.5 and 26.8%, respectively). In the younger age-group, non-responders had the same socioeconomic pattern in smoking as the responders. Independent of socioeconomic group, there was a tendency of ill or disabled smokers to respond more quickly than healthy smokers. Using a postal questionnaire with a high non-response rate might lead to an overestimation of socioeconomic differences and an underestimation of smoking prevalence. PMID- 8367687 TI - Sex differences in response style to two self-report screening tests on alcoholism. AB - The revised Malmo modification of the Michigan Alcoholism Screening Test (Mm MAST) of 10 items including all four CAGE (an acronym for Cut down, Annoyed, Guilty, Eye-opener) items and one item on total sobriety was used in a health screening of a total birth-year cohort in Malmo. Seventy-two percent of the female and 68% of the male population participated. Nine hundred and eleven women and 911 men were included in the study population. The revised Mm-MAST yielded a higher proportion of scores indicative of problem drinking than the CAGE in both sexes; 4% of the women and 17% of the men had positive Mm-MAST scores (> or = 3 yes-answers). Rates of positive CAGE scores (> or = 2 yes-answers) were 1% and 7%, respectively. Frequencies of problem drinking in the Mm-MAST and CAGE positive scorers, respectively were similar for both women and men. The reliability of the revised Mm-MAST was better in the male population producing a Cronbach's alpha coefficient of 0.69 compared with 0.58 in the female population. In men the four CAGE items had the highest item-total scale correlations, which was found in only one CAGE item in women. We suggest that the revised Mm-MAST is a better screening instrument than the CAGE in both sexes. Nevertheless the reliability of the total revised Mm-MAST was poorer in women and the need for a female oriented alcohol questionnaire is promoted. PMID- 8367688 TI - Social differences in reproductive health. A study on birth weight, stillbirths and congenital malformations in Denmark. AB - AIM: To describe differences in life style variables according to socioeconomic groupings and to analyse the association between birth weight, stillbirth and congenital malformation according to the socioeconomic grouping for the father as well as the mother. METHOD: Follow-up of 11,888 pregnant women in Odense and Aalborg, Denmark who were consecutively enrolled in the study from April 1984 to April 1987 as part of a community trial. DATA: Information on socioeconomic group and life-style factors were collected by means of self-administered questionnaires in the 36th week of gestation. Data on pregnancy outcomes were collected from birth certificates and medical records according to standardized search routines. RESULTS: Women in the lower socioeconomic groups were younger, smaller, had a higher prepregnancy weight, smoked more and had a higher intake of coffee during pregnancy than women in higher socioeconomic groups. Better off women, on the other hand, had a higher consumption of alcohol, fish, and vegetables. Low birth weight was found to be negatively correlated with socioeconomic grouping. The lowest birth weights were found among babies born to unskilled and unemployed women even after adjustment for smoking habits, prepregnancy height and weight and a number of other potential confounders. Stillbirth and the prevalence of congenital malformations was not associated with socioeconomic grouping, but the amount of information was very limited regarding these outcomes. PMID- 8367689 TI - Bicycle accidents often cause disability--an analysis of medical and social consequences of nonfatal bicycle accidents. AB - Social and medical consequences of 278 children and 264 adults injured in bicycle accidents and seen in two hospitals in Helsinki in 1985-86 were analyzed. Information was collected from patient records, by means of a special questionnaire and by telephone interview. A child outpatient required 1.7 and a child inpatient 3.0 physician visits on an average, while adults required 2.2 and 4.9 visits, respectively. The average duration of hospital stay was 8 days for hospitalized adults and 6 days for children. Rehabilitative care outside the hospital was received by 6% of the adult outpatients and 25% of the inpatients, but none of the injured children. The mean duration of work disability was 82 days among inpatients, 11 days among outpatients, 127 days among the inpatients injured in motor vehicle collisions and 65 days among inpatients injured in other bicycle accidents. Of inpatients 32% and of outpatients 5% reported persistent (> 6 months) disability. Persistent disability was recorded in 11% of children, in 47% of adults and in 67% of elderly inpatients. Most serious consequences were due to intracranial injuries in motor vehicle-bicycle collisions. Of the hospitalized bicyclists 4% suffered from severe cognitive and behavioural changes or sense impairment and of adult inpatients 3% suffered from permanent work disability. The average costs of health and social services were about FIM 1000 per adult outpatient and FIM 13000 per adult inpatient. In prevention high priority should be given to motor vehicle collisions, head injuries and injuries among the elderly bicyclists. PMID- 8367690 TI - Lung cancer among butchers and slaughterhouse workers. AB - The following three questions are examined in this critical evaluation of the literature on lung cancer among butchers: (i) do butchers have an excess risk of lung cancer, (ii) if yes, is this excess possibly caused by exposures in the work environment, and (iii) if yes, what then are the possible etiologic exposures? It was concluded that butchers probably have an excess risk of lung cancer. This excess risk can be explained partly, but not entirely, by tobacco smoking. The following four possible etiologic exposures are introduced: human papilloma viruses, nitrite, incomplete combustion products, and fumes from meatpacking materials. Three of these possible explanatory factors (nitrite, combustion products and fumes from packing) are not, or only to a limited extent, substantiated by the empirical data. It was recommended that the hypothesis concerning human papilloma viruses and also the possible role of work stress be tested in future studies. PMID- 8367691 TI - Relationship between birthweight and occupational exposure to cytostatic drugs during or before pregnancy. AB - The birthweight of babies whose mothers were exposed to cytostatic drugs during pregnancy was compared with that of infants whose mothers were not so exposed. The study was conducted in four French hospitals and covered 420 singleton live births to 466 women. One hundred and seven of the 420 births were exposed before or during pregnancy; 298 were not. Information about exposure was not available for the other 15. The mean birthweight of the babies of exposed mothers was 85 g lower than that of infants of unexposed mothers, but the difference was not statistically significant (95% CI -192.2-22.2 g). When gestational age and conventional risk factors were taken into account, the adjusted difference in the means of the birthweights was -56 (95% CI -155.1-43.1) g. PMID- 8367692 TI - Blood lead concentrations of Swedish preschool children in a community with high lead levels from mine waste in soil and dust. AB - The lead concentration in capillary blood was investigated in 49 preschool children (0.7-7.4 years of age) visiting a day-care center in a Swedish community with high lead contamination from mining and milling in soil and dust in populated areas [up to 1400 and 14,000 micrograms.g-1 (6.76 and 67.63 mumol.g-1) of dry weight, respectively]. The blood lead levels were examined twice (in April and in September) in 33 of the children. The lead levels were low on both sampling occasions [arithmetic mean 31 (SD 13, median 30, range 13-79) micrograms.l-1, ie, arithmetic mean 0.15, (SD 0.06, median 0.14, range 0.06-0.38) mumol.l-1]. Whereas children up to four years of age showed significantly increased levels from April to September, a significant decrease was seen in older children. The level of lead in soil at home, gender, smoking habits at home, and estimated level of hand-to-mouth activity did not appear as strong determinants of lead in blood. The results indicate that lead from mine waste in soil and dust fallout does not constitute a significant health hazard for preschool children in Falun. PMID- 8367693 TI - Work-related agricultural fatalities in Australia, 1982-1984. AB - Work-related agricultural fatalities were examined as part of a larger population based study of all work-related fatalities in Australia in the period 1982-1984. A total of 257 farm-related fatalities were identified, of which 223 were deaths of persons in the employed civilian labor force (19.4 deaths per 100,000 persons per year) and 34 were deaths of children less than 15 years of age. The fatality incidence was higher among men, older age groups, and nonmanagers in general and in certain occupations in particular. Mobile mechanical equipment (particularly tractors) was the main fatal agent, roll-overs accounting for many of the fatalities. Better provision of information to agricultural workers, improvements in compliance to and enforcement of legislation, and changes in farming work practices are recommended to improve the safety of farms and farm work. PMID- 8367694 TI - Morbidity among unemployed and work-incapacitated men in The Netherlands. AB - As yet, the relationship between unemployment and physical health has not sufficiently been clarified. With a longitudinal approach a representative Dutch panel study and a study on a health center population were carried out. They involved work-incapacitated and unemployed men between 21 and 65 years of age. Men incapacitated for work were in poorer health than matched working men; the same was true in a three-year follow-up. Unemployed and working men were shown to be equally healthy. The physical health of the incapacitated men decreased with time but that of the unemployed men did not. This finding implies that unemployment per se does not lead to poorer health. Differences in social security systems seem to interfere with an international comparison of the consequences of unemployment on health. International research should distinguish more explicitly between those who are unemployed for economic reasons or incapacitated for work for medical reasons. PMID- 8367695 TI - Urinary styrene in the biological monitoring of styrene exposure. AB - The urinary excretion of styrene represents a promising indicator of exposure to this solvent. Nevertheless extensive research under field conditions is scant. In this investigation 214 styrene-exposed workers from 10 fiberglass-reinforced plastics factories were studied. Environmental monitoring was performed by personal passive sampling. Blood styrene and the urinary excretion of styrene and its main metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA), were measured. The correlation coefficient between the time-weighted average of environmental styrene and the mean urinary excretion of styrene was 0.88 (0.91 after logarithmic transformation), compared with the 0.82 and 0.78 of the end-of shift MA and PGA values, respectively. A high correlation (0.86) was also found between styrene in the blood and urine. The results, obtained under field conditions with a large group of exposed workers, confirm the usefulness of the urinary excretion of styrene as an exposure index for the biological monitoring of styrene exposure. PMID- 8367696 TI - Toxicokinetics and biological monitoring in experimental exposure of humans to gaseous hexahydrophthalic anhydride. AB - Six healthy volunteers were exposed to gaseous hexahydrophthalic anhydride (HHPA) concentrations of 10, 40, or 80 micrograms.m-3 (65, 260 or 520 nmol.m-3, respectively) for 8 h. The respiratory uptake of the inhaled HHPA was almost complete. Rapid increases in plasma and urinary levels of hexahydrophthalic acid (HHP acid) were seen. During the first 4 h after the end of exposure, the half time of HHP acid in plasma was about 2 h. A corresponding decay was seen in urine. The correlations (r > 0.90) between the air concentrations of HHPA and the levels of HHP acid in plasma and urine were close. They were even closer (r > 0.96) when the total respiratory uptake of HHPA was used. Urinary pH adjustment by intake of ammonium chloride or sodium hydrogen carbonate did not significantly alter the excretion of HHP acid. The results show that the analysis of HHP acid in plasma or urine is useful as a biological monitor for exposure to HHPA. PMID- 8367697 TI - Iterative use of a priori exposure matrices to improve the characterization of chemical exposures in agricultural work studies. AB - To assess pesticide exposures of agricultural workers, a priori exposure matrices based on "circumstantial determinants" of pesticide use were incorporated into the questionnaire of a case-referent study. Circumstantial determinants (crops cultivated, their surface areas and crop infestations) were recalled more frequently than specific chemicals. After the matrices were applied, the proportion of missing values fell from 44 to 9% for specific chemicals, from 97 to 17% for the dose for each treatment, and from 80 to 16% for number of treatments per year in a random sample of 40 questionnaires. The number of workers changed from 19 to 30 for parathion use, from 4 to 10 for mancozeb use, and from 4 to 12 for DDT (dichlorodiphenyltrichloroethane) use when the matrix was applied. The matrix enabled exposure levels to be assigned in each case. Provided that the matrix used is valid, this approach could increase the efficiency of case-referent studies on agricultural exposure to chemicals. PMID- 8367698 TI - Effect of the reduction of skin contamination on the internal dose of creosote workers exposed to polycyclic aromatic hydrocarbons. AB - Ten creosote-exposed workers of a wood impregnation plant participated in this study, which took place in two consecutive weeks on a Monday, after a weekend off. On one of the two days each worker wore Tyvek coveralls underneath his normal workclothes. Dermal contamination measurements (pyrene on exposure pads) and biological monitoring (urinary 1-OH-pyrene) were performed to measure the reduction of both the skin contamination and the internal dose. The total pyrene skin contamination of workers not wearing coveralls ranged between 47 and 1510 micrograms.d-1 (0.2-7.5 mumol.d-1). On the average, the coveralls reduced the pyrene contamination on the workers' skin by about 35 (SD 63)%. The excreted amount of 1-OH-pyrene in urine decreased significantly from 6.6 to 3.2 micrograms (30.2 to 14.7 nmol). Multiple regression analysis showed that skin contamination by polycyclic aromatic hydrocarbons is the main determinant of the internal exposure dose of creosote workers. PMID- 8367699 TI - Validity of self-reported exposures to work postures and manual materials handling. Stockholm MUSIC I Study Group. AB - Exposure data from self-administered questionnaires on manual materials handling and work postures were validated in relation to direct measurements and systematic observations on 39 men and 58 women representing 45 different occupations. The agreement was tested at a dichotomous level and, when possible, with quantification of duration or frequency. At the dichotomous level the agreement was "acceptable" for nine variables concerning work postures and the handling of loads weighing > 5 kg. No variable showed "acceptable" agreement when the duration or the frequency was quantified in more detail (4- to 6-point scales). Musculoskeletal complaints seemed to introduce a differential bias for some lifting variables. Thus some variables for postures or the handling loads of > 5 kg may, under certain conditions, be acceptable for use in epidemiologic studies when the relative risks are high. However, self-reported exposure seems to be too crude if more-detailed information is required. PMID- 8367700 TI - [Side effects of non-steroidal antirheumatic agents in the lower intestinal tract]. AB - Side effects of non-steroid anti-inflammatory drugs (NSAIDs) on the lower intestinal tract are reviewed. NSAID use may exacerbate or reactivate quiescent inflammatory bowel disease. There are distinct types of NSAID-induced enterocolitis: ulcerative colitis, Crohn's disease, and necrotizing enterocolitis in premature infants. It is also suggested that NSAIDs may play an etiological role in collagenous colitis. Furthermore, NSAIDs may induce ulcerations, perforations and strictures in the small as well as large bowel. Occult and severe blood loss from lower intestinal tract under treatment with NSAIDs should be kept in mind. PMID- 8367701 TI - [Bronchiolitis obliterans organizing pneumonia (BOOP)--chronic organized pneumonia (COP). Diagnosis, therapy and course]. AB - Cryptogenic organizing pneumonia (COP) or bronchiolitis obliterans organizing pneumonia (BOOP) designates a disease characterized by particular histopathological features. Symptoms and clinical findings are more or less typical and the etiology of the disease is unknown in most of the cases. We report on 7 patients in whom the diagnosis was established by open lung biopsy during a workup for persistent pulmonary infiltrates. The clinical findings, the radiological features and the course during treatment with corticosteroids are analyzed. In all patients the symptoms improved. In two cases we observed relapses after discontinuing the corticosteroids or diminishing the dose. These relapses again responded to steroids, but in one patient progressive pulmonary restriction was noticed despite continuous treatment. PMID- 8367702 TI - [Hemolytic-uremic syndrome in children: a 19-year retrospective study]. AB - Forty-two children (22 girls and 20 boys, ranging in age between 2 months and 13 years, median age 17 months) were admitted with acute hemolytic-uremic syndrome to the University Children's Hospital, Berne from 1973 to 1991. Seventeen patients developed hypertension and 30 renal failure. Three out of the 19 cases necessitating acute dialysis progressed to end stage renal failure. Four out of the 7 patients with signs of severe central nervous system involvement died. The initial clinical course was consistently more favourable in 35 patients with diarrheal prodrome. Increased protein excretion in association with high blood pressure was observed in 4 patients with initial favourable course who were examined one year after disease onset. This study indicates the generally favourable immediate prognosis of childhood hemolytic uremic syndrome and the possible persistence of high blood pressure and pathological proteinuria on follow-up. PMID- 8367703 TI - [Recurrent, life-threatening anaphylaxis as initial manifestation of cystic echinococcosis (granulosus) of the liver]. AB - A 34-year-old, previously healthy Yugoslav developed relapsing generalized anaphylactic reactions associated with life-threatening laryngospasm. After successful life support with volume-replacement, epinephrine, antihistamines and steroids, clinical workup disclosed a slight tenderness in the right upper abdomen and sonography a polycystic tumor with coarse calcification within the wall. The presumptive diagnosis of cystic liver echinococcosis with spontaneous rupture of a hydatid cyst was confirmed surgically and serologically. This case history shows that liver echinococcosis should be considered in otherwise unexplained anaphylaxis. PMID- 8367704 TI - [Cerebrovascular symptoms in a patient with an aneurysm of the internal carotid artery, aneurysm of the inter-atrial septum, patent foramen ovale and redundant Eustachian valve]. AB - We describe for the first time the combination aneurysm of the internal carotid artery, atrial septal aneurysm, patent foramen ovale and redundant eustachian valve in the right atrium. The presenting symptoms and clinical course are briefly outlined. The consequences of the cardiac findings are discussed. PMID- 8367705 TI - [Prevention of cardio-embolic cerebral infarcts: simple, but...]. PMID- 8367706 TI - [Heterogeneity of involutional osteoporosis]. AB - Bone tissue mineral content (BTMC) was measured on transiliac bone biopsies by a combined microradiographic-microdensitometric technique. The samples originated from 69 osteoporotic postmenopausal women aged 42-86 (mean age 63 years). The diagnosis of osteoporosis was based upon a previous in-hospital screening. Results demonstrated a clear heterogeneity of BTMC values in osteoporotic women as compared with an age-related decrease in 31 age- and sex-matched controls. No correlation with clinical parameters could be found: Therapeutic issues raised by this study are discussed. PMID- 8367707 TI - [Liver biopsy in ambulatory patients. Diagnostic value in comparison to conventional and quantitative liver function tests]. AB - In this retrospective analysis we investigated the diagnostic yield of 148 consecutive liver biopsies performed as an outpatient procedure. In 144 patients, adequate specimens for histologic analysis were obtained. In these patients, 226 diagnoses were entertained. Clinical diagnosis was confirmed in 49.3%, modified in 43.8% and altered in 6.9%. Liver biopsy was particularly helpful in patients where an alcoholic etiology was suspected, since this could be confirmed in only 59.4% while in the others different, often treatable, causes of chronic liver disease were found. Neither conventional nor quantitative liver tests (galactose elimination capacity, aminopyrine breath test) served to differentiate reliably between severe and mild lesions. We conclude that liver biopsy remains an important diagnostic tool in patients with chronic liver disease, and that it can be safely performed on an outpatient basis in appropriately selected patients. PMID- 8367708 TI - [Simultaneous occurrence of lymphocytic gastritis and lymphocytic colitis with transition to collagenous colitis]. AB - Lymphocytic gastritis and lymphocytic colitis are two rare disorders of unknown etiology, only diagnosable by histology. Simultaneous occurrence of lymphocytic colitis and lymphocytic gastritis has not been described up to now. A 69-year-old female patient was examined because of crampy abdominal pain and watery diarrhea. Laboratory tests did not reveal an etiology and in colonoscopy the colon and terminal ileum were normal. Histology disclosed lymphocytic colitis. Esophagogastroduodenoscopy showed erosive bulbitis. Biopsies of the stomach revealed lymphocytic gastritis. A second colonoscopy one year later showed the development of collagenous colitis. PMID- 8367709 TI - [A balance assessment of the president of the commission for continuing education. Interview by Kurt Venner]. PMID- 8367710 TI - [The number of patients is generally falling off due to the recession. Interview by Kurt Venner]. PMID- 8367711 TI - [Those absent are really wrong!]. PMID- 8367712 TI - [The dental filling therapy of carious deciduous molars: materials and methods. A review]. AB - There is little consensus as to which restorative material or techniques are best suited to restore primary teeth. Techniques developed for the permanent dentition can seldom be applied to the primary teeth because of morphological differences and lack of cooperation by the children. The morphological properties of primary molars are discussed in this paper in relation to their therapeutic consequences. In addition to general guidelines for dental therapy in children, current restorative materials and techniques are compared regarding their suitability for the primary dentition. Finally the goals for the development of an ideal restorative material are formulated. PMID- 8367713 TI - [Mercury vapors from premeasured amalgam capsules]. AB - 12 dental amalgam capsules were tested for mercury leakage during trituration, storage, and disposal. The pertinent measurements were taken using two different measuring systems, both of which were based on the principle of optical absorption. While the results were excellent for half of the encapsulated products, some were deficient with respect to impermeability or safe handling. Five products cannot be recommended for regular use in the dental office. Overall, dental amalgam capsules of the latest product generations release lower mercury vapors; however, there are always exceptions, which is why periodical checks are recommended to protect the dentist and his or her team from avoidable exposure to mercury vapors. PMID- 8367714 TI - Innervation of root dentine in human premolars. AB - Based on autoradiographic studies it is generally held that the mammalian root dentine is only sparsely innervated. Previous electron microscopic studies on human teeth did not reveal nerve fibres beyond radicular predentine. It is the purpose of this communication to provide ultrastructural evidence for the presence of nerve fibres in apical root dentine of human premolars. Two healthy mandibular second premolars, removed due to orthodontic reasons, which formed part of a previous study, were utilized for this investigation. Root discs of about 0.6 mm thickness were removed at about 2 mm cervical to the root apex and processed for light and electron microscopy. Transmission electron microscopic examination revealed numerous nerve fibres along the pulp-predentine border and in patches of predentine. Distinct nerve fibres were observed in the inner mineralized portion of the radicular dentine. The axons existed in close association to the odontoblastic processes, but no synaptic contacts or junctional complexes could be observed. PMID- 8367715 TI - [The marginal adaptation and wear resistance of a fine hybrid composite inlay in vitro]. AB - A lab and a production batch of a new fine hybrid composite material were tested in adhesive MOD inlays. Using a long term in vitro test the wear resistance of both formulations and the marginal adaptation of the production batch were quantitated. The wear results were compared to the results generated with an amalgam control. The initial marginal adaptation in enamel was excellent totaling 95.9% (occlusal) to 99.5% (axial) of "continuous margin" at the tooth/cement interface. These values slightly decreased after loading to 81.4% (occlusal) and 93.8% (axial), respectively. In dentine however, insufficient marginal qualities were found (32.0% "continuous margin" initial and 18.9% after loading). The adhesion between inlay and composite cement was excellent and load stable. Both composite batches were significantly more wear resistant than the amalgam control and abraded the opposing enamel cusps significantly less than amalgam. PMID- 8367716 TI - [The interference with cardiac pacemakers from electrical devices]. PMID- 8367717 TI - [Dental ceramic inlay fillings. Expanded indications for dental ceramic inlay fillings]. PMID- 8367718 TI - A thin lifeline to genome researchers. PMID- 8367719 TI - New Seveso findings point to cancer. PMID- 8367720 TI - NSF balks at grants to entrepreneurs. PMID- 8367721 TI - Learning how to suppress cancer. PMID- 8367722 TI - Breaking the code for the tuberculosis invasion. PMID- 8367723 TI - Catalysis: design versus selection. PMID- 8367724 TI - Regioselective and enantioselective epoxidation catalyzed by metalloporphyrins. AB - Recent progress in regioselective and enantioselective epoxidations catalyzed by metalloporphyrins is discussed here, with an explanation of the biomimetic antecedents of this area and its relevance to synthetic applications. Classification of the catalysts that have been studied allows useful conclusions to be drawn about the development of this field. In particular, both the most promising biomimetic and practical catalysts have arisen from systems that can be systematically modified by convenient synthetic methodology. PMID- 8367725 TI - NF-kappa B activation by ultraviolet light not dependent on a nuclear signal. AB - Exposure of mammalian cells to radiation triggers the ultraviolet (UV) response, which includes activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B). This was postulated to occur by induction of a nuclear signaling cascade by damaged DNA. Recently, induction of AP-1 by UV was shown to be mediated by a pathway involving Src tyrosine kinases and the Ha-Ras small guanosine triphosphate-binding protein, proteins located at the plasma membrane. It is demonstrated here that the same pathway mediates induction of NF-kappa B by UV. Because inactive NF-kappa B is stored in the cytosol, analysis of its activation directly tests the involvement of a nuclear-initiated signaling cascade. Enucleated cells are fully responsive to UV both in NF-kappa B induction and in activation of another key signaling event. Therefore, the UV response does not require a signal generated in the nucleus and is likely to be initiated at or near the plasma membrane. PMID- 8367726 TI - Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice. AB - Expression of either the CD4 or CD8 glycoproteins discriminates two functionally distinct lineages of T lymphocytes. A null mutation in the gene encoding CD4 impairs the development of the helper cell lineage that is normally defined by CD4 expression. Infection of CD4-null mice with Leishmania has revealed a population of functional helper T cells that develops despite the absence of CD4. These CD8- alpha beta T cell receptor+ T cells are major histocompatibility complex class II-restricted and produce interferon-gamma when challenged with parasite antigens. These results indicate that T lymphocyte lineage commitment and peripheral function need not depend on the function of CD4. PMID- 8367727 TI - Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells. AB - Mycobacterium tuberculosis infects one-third of the world's human population. This widespread infection depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. DNA sequences of M. tuberculosis have been cloned; these confer on a nonpathogenic Escherichia coli strain an ability to invade HeLa cells, augment macrophage phagocytosis, and survive for at least 24 hours inside the human macrophage. This capacity to gain entry into mammalian cells and survive inside the macrophage was localized to two distinct loci on the cloned M. tuberculosis DNA fragment. PMID- 8367729 TI - [Results of treatment of polytraumatized patients. A comparative analysis of 3,406 cases between 1972 and 1991]. AB - The treatment data on 3,406 patients with multiple injuries were analyzed retrospectively from the viewpoint of quality control. The diagnosis, therapy, complications and course were documented and the treatment results of two decades (1972-1981 and 1982-1991) compared. Young people with an average age of 31 years were mostly affected: 86% had fractures (40% open injuries), 69% head injuries and 62% thoracic trauma. Head injury together with thoracic trauma was the most frequent injury combination and affected the duration of ventilation therapy and the intensive care course. The relationship between the kind and severity of injury [categorized according to the Hannover Polytrauma Score (PTS)] and the lethality rate was significant. Preclinical treatment (infusion, intubation, thoracic tube) has increased in the past decade, and rescue time has been shortened. For the initial clinical diagnosis, ultrasound and the CT scan have been used more frequently. In patient treatment the elimination of massive hemorrhage still has first priority. Primary stabilization of long tubular bones, mostly of the lower limb, is aspired for. Volume therapy has changed over the last decade, so the risk of acute renal failure has been nearly eliminated. Nowadays late complications, e.g., multiorgan failure, are well in the foreground. Today at Hannover Medical School the average intensive care time is 13.7 days and the hospitalization time 31 days. When the two decades were compared, mortality was seen to have declined from 40% to 18%. In the future if the mortality rate is to be reduced further, this can only be done by treating the cause of post-traumatic organ failure. PMID- 8367728 TI - [Rehabilitation and reintegration of polytraumatized patients]. AB - In this randomized study we attempt to verify treatment results, rehabilitation and social reintegration of multiple trauma patients. Two to 4 years after the accident a clinical follow-up examination was carried out on 104 multiple trauma patients with an average age of 29.5 years who had 7.7 single injuries. Patients with injuries of the central nervous system still showed neurological disorders in 32%. The initially determined Glasgow Coma Scale did not correlate with the long-term prognosis of neurological disorders. Only 4 of 38 thoracic injuries had functional disorders-these patients had required long-term ventilation therapy (> 3 weeks). Former abdominal injuries showed no objective disorders in the follow up. Most of the injuries to the extremities (79.7%) healed without functional disorder. Only patients with lower limb injuries still had complaints. At the time of the checkup 6.7% had still not been able to work (for more than 24 months) and 26.9% for more than 12 months. The disability rate was less than 20% in 64.3%, 7.2% more than 50% and 9.6% more than 80%. Most of these patients had severe head injuries. There was a relationship between reintegration at work and the age of the patients: 49.2% of patients younger than 25 years were working in their previous profession, 26.9% had here re-educated, and only 7.9% were unemployed. However, in the age group older than 25 years, only 29.2% worked in their previous profession and 12.2% had been re-educated. This follow-up study shows that in multiple trauma patients reintegration at work and in social life is possible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367731 TI - [The LS-8 lever fixator: repositioning and fixation aids for dislocations and dislocation fractures of the lumbar spine and the thoracolumbar transition. Part I. Biomechanical considerations and surgical technique]. AB - We are reporting a lever-type internal fixateur, the LS-8 system, which can be used for reduction and stable fixation of fractures and fracture-dislocations of the thoraco-lumbar and lumbar spine. The LS-8 system is different from all previous systems: it combines the advantages of the spinal fixateur interne and conventional plate fixation, while largely avoiding their disadvantages, such as the fixed position of the screw hole and the mechanical overloading of the fixing points, as in the previous hook-type systems. In order to minimize these drawbacks, we have added a plate of variable length to our system, creating a fulcrum that prevents overloading. This means that the reinforced 8 mm diameter screws function as lever arms around this fulcrum, conducting and counterbalancing the active forces. As a result, the loading capacity of our system has been greatly improved. Since the LS-8 "lever fixateur" is a reinforced system, it is no longer necessary to use any plaster or brace fixation. We should like to illustrate the advantages and the capability of the LS-8 system by presenting one of our cases. PMID- 8367730 TI - [Results of dorsal pelvic ring stabilization]. AB - Complete disruptions of the posterior pelvic ring are rotationally and vertically unstable [type C according to the Tile/AO (ASIF) classification (1991)]. Usually operative treatment is required. The data on 24 patients over a 5-year period were analyzed. Thirteen patients were female (54.2%) and 11 male (45.8%); the average age was 32.8 years. Multiple trauma was present in 20 patients (83.3%). In most cases operative stabilization of the posterior pelvic ring was performed by lag screws from the ilium into the body of the sacrum. The mortality in this series was 16.7% (4 patients). One patient had a thrombosis of the femoral and pelvic veins. In 2 patients we had to perform a second operative procedure because of lag screws that had not been precisely placed or had dislocated. Two incisions healed secondarily. On the postoperative radiographs in 3 patients a slight deformity of the pelvic ring was visible; in another patient the reduction of the injured hemipelvis was not sufficient. The 20 survivors had a clinical and radiological examination on average 27.5 months after their injury. Eleven patients were without pain, while 9 complained of low back pain. Gait disturbances were found in 8 patients; in 2 of them this was due to associated injuries. Five patients were unable to work. Eight patients had neurological deficits, some of them minor. Additional complications were impotence (3 patients), urinary (2 patients) or fecal incontinence (1 patient), and dystocia requiring a cesarean section (1 woman) [multiple entries].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367732 TI - [Development of thromboses in hip joint endoprostheses. A study with color-coded duplex ultrasound]. AB - After 102 hip replacements in a surgical technique that avoids bone-marrow intravasation as much as possible, color-coded duplex sonography revealed thigh thrombi in only 4 cases without any signs of thrombosis. This rate is lower than that found in all other comparable studies. The investigations stress the role of bone-marrow intravasation in the induction of deep vein thrombosis in hip replacement. With an optimal surgical technique, thigh thrombi can be greatly reduced in hip replacements, which have a higher rate than all other operations. PMID- 8367733 TI - [Reliability of clinical examination of the shoulder in comparison with arthroscopy. A prospective study]. AB - The results of clinical shoulder examination including 20 special tests were compared with subsequent arthroscopic findings in 45 patients. The sensitivity of the clinical diagnosis was 73%. Impingement syndrome was correctly diagnosed in 19 of 22 cases (86%), rotator cuff tears in 7 of 9 cases (78%). The highest sensitivity for stage II impingement was found for the supraspinatus test (85%) and the lift-up test (92%); the sensitivity of these tests for rotator cuff tears was 100% and 89% respectively. Differentiation between impingement syndrome with and without rotator cuff tear by one of these tests alone was not possible because of their low positive predictive values (26% and 56%). In contrast, in 90% of patients with negative rotator tests the rotator cuff was complete, while the negative predictive value of the supraspinatus test was 100%. Instability was confirmed in only 53% of cases; the Leffert test had the highest positive predictive value (73%). In conclusion, the clinical diagnosis of a shoulder lesion cannot reliably be achieved by single tests; rather overall evaluation by an experienced clinician is necessary. PMID- 8367734 TI - [Rupture of the patellar ligament of the tibial tuberosity as a complication after cruciate ligament-plasty]. AB - We report a complication of a rupture of the patellar ligament at the tibial tuberositas following autologous cruciate ligament reconstruction. To our knowledge, this complication has not yet been described. PMID- 8367735 TI - [Blood lamination in bone cement--effect of cementing technique]. AB - The quality of the cement layer influences the long-term survival of cemented endoprostheses. However, blood and fluid laminations within the cement layer, which can form during implantation of endoprostheses, lead to the deterioration of bone cement. Since the bone cement is the weakest part in the construction consisting of prosthesis, bone and bone cement, further weakening of the bone cement should be avoided if possible. By means of in vitro studies, three different cementing techniques were tested, measuring quantitatively the amount of fluid within the cement layer after implantation. The least amount of fluid within the cement layer was found in the cement-canal technique, and the highest amount in anterograde cement injection. Retrograde cement injection led to intermediate values. PMID- 8367736 TI - [Para-basal metatarsal V fracture: conservative functional treatment]. AB - Fractures of the fifth metatarsal bone, mostly avulsion fractures that result from forced inversion of the plantar foot, are relatively common. There are two distinct types of fracture that involve the proximal portion of the fifth metatarsal bone. The first type is the proximal diaphyseal fracture, the so called Jones fracture, and the second type involves the area of the metatarsal tuberosity. They are usually not displaced or only slightly displaced. The standard treatment is a below-the-knee walking cast Osteosynthesis for fractures of the fifth metatarsal bone is indicated only in cases where significant displacement cannot be corrected by closed reduction. At the Department of Traumatology in the Stadtische Klinikum Braunschweig. 51 patients (32 male, 19 female) with an avulsion fracture of the proximal diaphyseal portion or a Jones fracture of the fifth metatarsal bone were treated functionally with a brace (Caligamed II). The average displacement was 1.4 mm (range 0.8-4.0 mm). In each case the fracture was treated for 2-3 days in a short leg cast and additional antiphlogistic medication was applied. After edema had been reduced, every patient was fitted with a carefully adapted Caligamed II brace, and this was followed by intense mobilization and walking therapy. The average follow-up in this study was 14.2 +/- 1.8 month. In this protocol the patients were examined at our clinic during the first week after trauma in order to check the brace again, again after 5-6 weeks for X-rays and to remove the brace, and for a final check up after 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367737 TI - Experience with prophylaxis in Germany. PMID- 8367738 TI - Experience with prophylaxis in Sweden. PMID- 8367740 TI - Prophylaxis: musculoskeletal evaluation. PMID- 8367739 TI - Cost-effectiveness--can it be measured? PMID- 8367741 TI - Radiographic scores and implications. PMID- 8367742 TI - Palpation of the thyroid gland. AB - The initial clinical clue to the existence of a disorder of the thyroid gland often is the detection of a physical abnormality of the gland. Adequate palpation of the gland is an essential component of the evaluation of a suspected disorder of the thyroid gland. Provided herein are guidelines that others have found useful in improving their skill in this aspect of physical diagnosis. PMID- 8367743 TI - Poor positive predictive value of low sensitive thyrotropin assay levels for hyperthyroidism in nursing home residents. AB - We assessed the positive predictive value of a low thyrotropin (TSH) level on sensitive TSH (STSH) assay as an indicator of hyperthyroidism. In 742 determinations on nursing home residents who were not taking thyroid hormone, we identified 15 with low TSH levels. None of the residents had a completely suppressed (undetectable) TSH level upon initial testing or an elevated total triiodothyronine (T3) or thyroxine (T4) level. Half the patients in whom total T3 was measured had low levels. Of 11 surviving residents, four subsequently had a normal TSH level and six others had a normal free T4 level. Only one patient had a slight elevation of the free T4 level. None of the residents were diagnosed as having hyperthyroidism. PMID- 8367744 TI - Assessment of nutritional status and obesity in elderly patients as seen in general medical practice. AB - Overweight and obesity are generally considered to have a negative impact on longevity because of their association with many diseases, including hypertension, diabetes, coronary artery disease, osteoarthritis, and certain types of cancer. Nevertheless, some authors, notably Ancel Keys, have concluded that being overweight improves one's chances for longevity. I studied 122 consecutive patients who had comprehensive geriatric assessment with regard to their body mass index, responses to Wolinsky's Nutritional Risk Index, and serum albumin levels. There was a high prevalence of overweight (60% of men and 45.6% of women). This fact, coupled with the observed low prevalence of underweight subjects, tends to support Keys' statement concerning the benefit of being overweight. However, the relative absence of significant obesity supports the impression that significantly obesity reduces prospects for longevity. Although serum albumin measurements were obtained for only 38 subjects, the fact that the value was low in only one instance--in the case of a person who was seriously ill -suggests that obtaining routine serum albumin measurements in ambulatory, community-dwelling elderly people is not cost-effective. PMID- 8367745 TI - Evaluation of endometrial biopsy using an aspiration curet without cervical tenaculum. AB - In a study of 132 women having endometrial biopsy with either a Novak or Randall aspiration curet before hysterectomy, a tenaculum was not used initially if the curet could be passed easily through the cervix. One biopsy specimen was taken from the anterior endometrium and one from the posterior endometrium. Biopsy was successful in 80 women (61%) and unsuccessful in 52 (39%). Women who are premenopausal, who do not have cervical stenosis, and who have a uterus that sounds to 3.5 inches or less are significantly more likely to have a successful biopsy. Excluding six women in whom the curet could not be passed through the cervix, adequate tissue for histologic evaluation was obtained in 101 of 126 women (80%). Furthermore, endometrial biopsy accurately reflected histopathologic features of the surgical specimen in 98% (98/101) of the women who had sufficient tissue obtained for evaluation. Endometrial biopsy done with an aspiration curet but without placing a tenaculum on the cervix should be attempted in women who require evaluation. Endometrial biopsy would appear to rival dilation and curettage for obtaining endometrial tissue that accurately reflects endometrial histopathology. PMID- 8367746 TI - Detection of fibrin D-dimer in plasma and urine of pregnant women using Dimertest latex assay. AB - Eighty-six women admitted for evaluation of preeclampsia had plasma and urine screened for the presence of fibrin D-dimer using the monoclonal antibody DD-3B6 in a latex fixation assay (Dimertest). In 53 of the women screened, results were negative for fibrin D-dimer in both plasma and urine; in 33, results were positive in urine (N = 11), plasma (N = 14), or both (N = 8). D-dimer positive women were at increased risk for earlier delivery (mean 34 versus 36 weeks), lower birth weight babies (mean 2,327 versus 2,669 g), higher mean arterial pressures (mean 104 versus 94mm Hg), liver function test abnormalities (mean lactate dehydrogenase value 256 versus 142 U/L, mean serum glutamic-oxaloacetic transaminase 67 versus 23 U/L), and significantly elevated levels (> 40 micrograms/mL) of fibrin(ogen) degradation products (FDPs). Interestingly, 22 of 33 D-dimer positive women had insignificant levels of FDPs. Generally, D-dimer negative women had no significant abnormalities in results of coagulation tests and liver function tests. This study confirms previous observations on the value of D-dimer detection in screening for preeclampsia coagulopathy and extends this tool to its detection in urine. PMID- 8367747 TI - Prayer and health during pregnancy: findings from the Galveston Low Birthweight Survey. AB - In this study we examined the relationship between praying for one's baby during pregnancy and self-ratings of health. Data were collected from a biethnic (black and Hispanic) sample of postpartum mothers in Galveston, Tex, from 1986 to 1987. This sample is representative of the annual biethnic population of live births in Galveston. Subjective health was assessed for the periods both before and during pregnancy with self-ratings of global or overall health, worry over health, and functional health or lack of disability. Analyses controlled for the effects of the mother's age, marital status, gravidity, education, and self-rated religiosity. Findings revealed that all three prepregnancy health measures were associated with prayer. Subjectively unhealthier mothers prayed more for their baby during pregnancy regardless of their perceived health during pregnancy, and subjectively healthier mothers prayed less for their baby regardless of their self-reported religiosity. Additional analyses revealed that the effect of poor health on the frequency of prayer was not simply an outcome of the mother's worry over her own health. PMID- 8367748 TI - Immediate orthostatic hypotension: diagnostic value in acutely ill patients. AB - Hypotension (systolic blood pressure less than 90 mm Hg) was induced immediately in 21 acutely ill normotensive patients when they were raised from a supine to an upright position. Systolic blood pressure declined to 80 mm Hg or lower in all patients and to 65 mm Hg or lower in 10 patients when they assumed an upright posture. Immediate orthostatic hypotension observed in 9 patients suggested hypovolemia, which was promptly corrected by rapid infusion of large volumes of normal saline and/or albumin. Orthostatic hypotension was of diagnostic aid in 16 patients, including 4 with infections (pelvic inflammatory disease, occult septic shock, legionnaires' disease, Rocky Mountain spotted fever), 3 with adrenal insufficiency, 2 with acute myocardial infarction, 1 with hypoglycemia, 2 with severe cardiac valvular obstruction, and 4 with inappropriate drug use (enalapril or trazodone). These findings suggest that immediate orthostatic hypotension in acutely ill patients is a physical sign that might have valuable diagnostic and therapeutic implications. PMID- 8367749 TI - Group psychotherapy for patients with dementia. AB - Some of the goals of our group psychotherapy sessions on the inpatient unit include (1) creation of an emotional climate of acceptance and warmth that helps patients learn to accept themselves and their feelings, (2) frequent intervention by the group facilitator/therapist to help facilitate social interaction for patients whose communication ability is impaired, (3) opportunity for patients to experience the feeling of belonging, of being part of a group, (4) opportunity for patients to ventilate feelings and rediscover mutual kinds of experience, (5) opportunity for patients to reminisce about past accomplishments and give new meaning to their current lives, and (6) creation of a platform for patients to achieve a sense of self by expressing personal opinions in an environment of respect and acceptance. The outcome of group therapy for demented as well as nondemented patients should be increased ability to cope with losses at several levels, promotion of new skills, increased adaptation skills, and increased ability to accept change. We also want patients to learn to express feelings and to realize that the expression of feelings can have a positive outcome (relief from repression, clarification of ambivalence, solutions, etc). PMID- 8367750 TI - Dementia: physician approaches to the caregiver's problems. AB - The demented patient requires medical and often psychiatric supervision, but the caregiver is often neglected. This article identifies special issues for caregivers that may need attention from the demented patient's physician. The physician's attention can benefit both the patient and the caregiver and save the physician valuable time. PMID- 8367751 TI - Medical shortages and Confederate medicine: a retrospective evaluation. AB - The Union's decision to treat medicines and medical supplies as contraband of war meant, for the Confederacy, the specter of medical shortages. The Confederate medical department significantly lessened the subsequent suffering through an energetic and resourceful program to supply its physicians' needs. Medicines and medical supplies were purchased abroad and smuggled through the Union blockade, obtained in an illicit trade with the North, captured from the enemy, and manufactured in the Confederacy. The search for home remedies, enthusiastically endorsed by Surgeon General Samuel P. Moore, was one of the most prominent features of the southern program. This paper surveys and analyzes medical shortages and Confederate medicine. PMID- 8367752 TI - Hemobilia in systemic lupus erythematosus. AB - Symptoms of acute cholecystitis developed in a 22-year-old woman with active SLE. Abdominal ultrasonography and biliary patency scan showed evidence of acalculous cholecystitis and common bile duct obstruction, respectively. Operation revealed acalculous cholecystitis and hemobilia; a liver biopsy specimen also showed hemobilia. Surgery relieved the patient's symptoms. This case demonstrates a new complication of SLE. PMID- 8367753 TI - Pneumonia due to Pneumocystis carinii in a transplant recipient with normal arterial oxygen tension and normal radiographic findings. AB - We have described an exogenously immunosuppressed, HIV-negative patient with a subacute presentation of Pneumocystis carinii pneumonia characterized by normal arterial oxygen tension and alveolar-arterial oxygen gradient and normal findings on serial chest radiographs. This case demonstrates that other studies in addition to chest radiograph and resting arterial blood gas measurement are necessary in all immunosuppressed patients with progressive respiratory symptoms, regardless of cause of immunosuppression, to exclude P carinii pneumonia from the differential diagnosis. PMID- 8367754 TI - Sarcoidosis: unusual cause of a rectal mass. AB - We have reported the case of a patient who had a rectal mass 3 years after the diagnosis of sarcoidosis. A malignancy was suspected, but biopsy of the rectal mass showed epithelioid granulomas with giant cells, consistent with sarcoidosis. Therefore, sarcoidosis should be considered as a rare cause of a rectal mass. PMID- 8367755 TI - Cogan's syndrome manifesting as sudden bilateral deafness: diagnosis and management. AB - Cogan's syndrome is an uncommon entity of nonsyphilitic interstitial keratitis with vestibulo-auditory disturbances. Although it is unusual, Cogan's syndrome should be considered in the differential diagnosis of patients with sudden hearing loss, even when they lack ophthalmologic symptoms. Systemic manifestations are not uncommon and, along with serologic and hematologic abnormalities, may help in making the diagnosis, which requires a high index of suspicion. Treatment with steroids has largely been based on symptoms. We suggest using the C-reactive protein level as a monitor of subclinical disease activity; it is therefore beneficial in the adjustment of steroid therapy. We have described the case of a 41-year-old woman who sought treatment for an upper respiratory infection syndrome and severe vertigo. Evaluation included hematologic and serologic studies, lumbar puncture, and CT and MRI scans. Abnormal findings consisted of an elevated white blood cell count and an ESR of 112 mm/hr. Six days later, profound, bilateral sensorineural hearing loss developed suddenly. Intensive corticosteroid and vasodilator therapies were instituted, but there was no improvement in hearing levels. Ten days later eye pain and redness developed, and ophthalmologic evaluation revealed an interstitial keratitis consistent with Cogan's syndrome. Steroid eye drops and oral prednisone therapy promptly relieved the eye symptoms. Steroid tapering was associated with diffuse joint pain and swelling consistent with a systemic vasculitis. After rheumatologic consultation, steroid dosage was titrated to the CRP level and ESR, and vasculitic symptoms resolved. Hearing levels did not improve, and the patient had cochlear implantation. Thirteen cases of bilateral sudden deafness due to Cogan's syndrome have been reported previously. This is the first case in which there were no immediate eye symptoms. PMID- 8367756 TI - Pneumothorax and bronchopleural fistula during treatment of allergic bronchopulmonary aspergillosis. AB - A man with allergic bronchopulmonary aspergillosis had pneumothorax and bronchopleural fistula while impacted mucus was being successfully dislodged from bronchiectatic airways. We believe this is the first report of pneumothorax with bronchopleural fistula in a patient with active ABPA, and we have proposed a mechanism to explain the development of this complication. PMID- 8367757 TI - Intracerebral hemorrhage after topical administration of mydriatic agents. PMID- 8367758 TI - Adenocarcinoma of the small intestine: a plea for early diagnosis. AB - The small bowel is a difficult organ to examine clinically and study diagnostically. The SBFT study is an adequate screening tool for evaluation of the small bowel, but if there is a moderate to high index of suspicion of an undetected tumor, enteroclysis is better than upper GI series with SBFT for preoperative diagnosis of such lesions. Based on the above findings, we recommend that any patient with symptoms and findings highly suggestive of small bowel tumor, especially chronic GI blood loss with a negative work-up, be viewed with a high index of suspicion and his case investigated aggressively, using enteroclysis followed by exploration. PMID- 8367759 TI - Cryptococcus albidus and mucormycosis empyema in a patient receiving hemodialysis. AB - C albidus and mucormycosis were cultured simultaneously from the pleural space of a patient with end-stage renal disease receiving long-term hemodialysis. There have been only nine previous reports of infection with C albidus, with only one involving the lung. This organism has never before been isolated from the pleural space, and none of the previously reported cases included a coinfection with mucormycosis. We have reviewed and compared all known cases of infection with C albidus. PMID- 8367760 TI - Ruptured ovarian artery aneurysm complicating a term vaginal delivery. AB - Ruptured ovarian artery aneurysm is rare. Of the eight cases previously reported, seven were diagnosed postpartum. Our case of a ruptured right ovarian artery aneurysm was associated with massive retroperitoneal bleeding. The probable time of rupture could be traced to the second stage of labor. This case indicates the need for early evaluation of atypical flank pain during labor. PMID- 8367761 TI - Nephrogenic adenoma of the ureter. PMID- 8367762 TI - Terbutaline pump treatment of premature labor. PMID- 8367763 TI - Green tobacco sickness. AB - Green tobacco sickness (GTS) is an occupational illness that causes significant morbidity in tobacco harvesters. Physicians need to be aware of GTS and its differential diagnosis, especially when patients come to emergency rooms. Dermal absorption of nicotine is reported to be the cause of GTS. No fatalities have been reported, and treatment is supportive. Prevention, by covering exposed skin, seems to be the most effective way of dealing with GTS. PMID- 8367764 TI - Retrospective comparison of outcome of 100 consecutive open cholecystectomies and 100 consecutive laparoscopic cholecystectomies. AB - If laparoscopic cholecystectomy is to be a viable option for community surgeons and their patients, it should have a safety profile similar to or better than that of open cholecystectomy. Morbidity and mortality from 100 consecutive open cholecystectomies were compared to morbidity and mortality from 100 consecutive laparoscopic cholecystectomies. All procedures were done at Davis Community Hospital (Statesville, NC, population 25,000). Open cholecystectomies were done by seven staff surgeons from July 1987 to March 1990. Laparoscopic cholecystectomies were done by three staff surgeons from February 1990 to August 1990. Cholangiography during open cholecystectomy was selective. After an initial learning experience of 11 cases, cholangiography was routine during laparoscopic cholecystectomy. Patients having cholecystectomy coincidental to a planned common duct exploration for stones or neoplasia were excluded. For open cholecystectomy, morbidity was 13% and mortality, 2%. For laparoscopic cholecystectomy, morbidity was 9% and mortality, 1%. One death after open cholecystectomy was due to pulmonary embolus. The other two deaths in the series were due to underlying severe cardiopulmonary disease. Complications related directly to cholecystectomy were bleeding requiring transfusion (open 2, laparoscopic 1), bile leak (open 1, laparoscopic 1), wound infection (open 1), and prolonged back pain (laparoscopic 2). In two patients, the laparoscopic procedure was converted to open cholecystectomy. There were no common bile duct injuries in either group of patients. Results of this study suggest that laparoscopic cholecystectomy can be done as safely as open cholecystectomy, even in smaller community hospitals. PMID- 8367765 TI - Symptoms of acid-peptic disease in children. AB - Esophagogastroduodenoscopy (EGD) is a useful procedure for the evaluation of gastrointestinal disease in pediatric patients. Indications for EGD in children are similar to those for adults. However, symptoms of acid-peptic disease reported by children may differ from those expressed by adults. Therefore, we sought to identify symptoms associated with acid-peptic disease in pediatric patients. The medical records of 114 children having EGD with biopsy were reviewed. The diagnosis, which included esophagitis, gastritis, duodenitis, ulcer, or normal, was based on histologic findings. Six symptoms correlated significantly with acid-peptic disease: epigastric pain, nocturnal pain, postprandial pain, water brash, weight loss, and a family history of peptic ulcer disease. Epigastric pain and nocturnal pain are the most sensitive symptoms of acid-peptic disease in pediatric patients. Fecal occult blood and hematemesis, although specific, are not sensitive indicators of acid-peptic disease in children. PMID- 8367766 TI - The relationship of facet tropism to degenerative disc disease. AB - The role of facet tropism (asymmetry) in the pathogenesis of degenerative disc disease is unknown, and several conflicting reports have been published. We studied this association using CT/discography performed at 324 lumbar levels (108 patients). The stage of disc degeneration as well as the patient's pain response upon discographic injection were scored using a standardized protocol. The facet angles were measured directly from the axial CT/discographic images and defined, in each case, as the angle formed by the facet orientation with respect to the midsagittal plane. The facet tropism angle was defined as the difference between the left and right facet angles at each disc level. The mean and standard deviation (SD) of the tropism angles were calculated. From this calculation, each pair of facet joints was classified as symmetric (within 1 SD of the mean), moderately asymmetric (between 1 and 2 SD), or severely asymmetric (beyond 2 SD of the mean). There were no differences in degree of disc degeneration or pain response with respect to the facet tropism. The total facet angle was also studied. The total facet angle was greater at the more caudal levels. The total angle size was not associated, however, with disc degeneration or pain provocation. These findings do not support the hypothesis that there is an association between facet tropism and degenerative lumbar disc disease. PMID- 8367767 TI - The effects of depth of penetration, screw orientation, and bone density on sacral screw fixation. AB - Obtaining adequate sacral fixation is an important and challenging clinical problem. Bicortical screw fixation has been used to provide improved mechanical strength. The goal of this study was to evaluate the effects of depth of penetration (unicortical versus bicortical), orientation (medial versus lateral), and bone density on the strength of the bone-screw interface. Seven-millimeter Steffee screws (Acromed, Cleveland, Ohio) were placed in human cadaveric sacra. The screws were placed either medially into the centrum of the S1 body or laterally into the sacral ala. The fixation systems used, either bicortical or unicortical, were tested on a Universal testing machine. The specimens were loaded to failure and biomechanical parameters were measured. Medially oriented screws sustained the highest load to failure. In an older population, unicortical fixation sustained load to failure and initial compliance findings were similar to those for bicortical fixation. The regional bone density in the centrum of the first sacral body was denser than that in the lateral alar region, and also provided more rigid bone screw fixation. PMID- 8367768 TI - Mechanics of interbody spinal fusion. Analysis of critical bone graft area. AB - Bone graft subsidence is a serious complication of interbody spinal fusion. In this study, 66 mechanical tests were performed on 35 thoracic vertebral bodies to investigate the in situ mechanics of interbody spinal fusion. The relationships among trabecular bone density, bone strength, and size of bone graft area were analyzed. All vertebral bodies were scanned by quantitative computer tomography (QCT) to determine their bone density before mechanical testing. The decorticated trabecular beds of the vertebral bodies, void of all posterior elements, were loaded in a manner similar to that which occurs after surgical interbody fusion. That is, rectangular blocks of polymethylmethacrylate, representing bone grafts, were used to transfer controlled compressive loads to the decorticated vertebral trabecular surface. Both destructive and nondestructive tests were performed. The relationship between QCT bone density and trabecular bone strength was related by a power function, and, on average, the bone density and trabecular bone strength were 0.137 g/cm3 and 3.97 MPa, respectively. Eighty percent of the vertebral bodies with graft covering 25% of the total end plate area or less failed at loads less than 600 N, while 88% of the vertebral bodies with 30% or greater covered were able to carry a load greater than 600 N. The results suggest that the intrinsic behavior of trabecular bone loaded within the vertebral body is little different from the behavior of the whole body, that QCT bone density is indicative of bone strength, and that interbody graft area should be significantly greater than 30% of the total end plate area to provide a margin of safety.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367769 TI - A histologic study of lumbar pseudarthrosis. AB - Biopsy specimens were obtained from 35 consecutive patients undergoing pseudarthrosis repair after failed posterior spinal fusions. Biopsy specimens were obtained when possible from the fusion mass, from areas of motion, and from the lumbar facet remnant where identifiable. Tissue found between adjacent bony segments was noted to contain predominantly fibrous tissue often accompanied by signs of local fibrocartilaginous metaplasia. In addition, small fragments of impacted bone, sometimes seen to be undergoing active resorption, also were noted frequently in these areas. The bone adjacent to the areas of motion was sclerotic and poorly organized, containing a mixture of woven and lamellar bone. Interestingly, multiple microtrabecular fracture with appositional new bone formation was a frequently seen feature. All facet joint biopsies were noted to have evidence of degenerative disease. Both cartilage fissuring and significant chondrocyte cloning were noted. Subchondral bony sclerosis was also a consistent feature. PMID- 8367770 TI - Clinical methodologies and incidence of appropriate statistical testing in orthopaedic spine literature. Are statistics misleading? AB - An analysis of 300 randomly drawn orthopaedic spine articles, published between 1970 and 1990, was performed to assess the quality of biostatistical testing and research design reported in the literature. Of the 300 articles, 269 dealt with topics of an experimental nature, while 31 documented descriptive studies. Statistical deficiencies were identified in 54.0% of the total articles. Conclusions drawn as the result of misleading significance values occurred in 124 experimental studies (46%) while 96 failed to document the form of analysis chosen (35.7%). Statistical testing was not documented in 34 studies (12.6%), while 20 (7.4%) employed analyses considered inappropriate for the specific design structure. PMID- 8367771 TI - Relationship of the dura, Hofmann's ligaments, Batson's plexus, and a fibrovascular membrane lying on the posterior surface of the vertebral bodies and attaching to the deep layer of the posterior longitudinal ligament. An anatomical, radiologic, and clinical study. AB - With the advent of computed tomography (CT) and magnetic resonance imaging (MRI), visualization of soft tissue structures in the spinal canal, which were previously undetectable, is possible. This study was undertaken to more accurately identify these soft tissue layers and to determine factors such as when is a disc contained and when is it not; in discography, when the disc leaks, into what layer is the contrast going; or when a nuclear fragment creeps upward or downward, just where is it. The works of Fick, Dommisse, Kikuchi, Schellinger, Hofmann, Batson, and Parke were studied. The professors of anatomy of four major medical schools were consulted along with several neuroradiologists and embryologists. Forty lumbar spines were dissected (20 fresh, 20 preserved). Magnetic resonance imaging scans were taken. Photographs and photomicrographs were made. A fibrous membrane, first mentioned by Fick, can be identified lying anterior to the posterior longitudinal ligament and attaching to the deep layer of the posterior longitudinal ligament. It has been given relatively little attention in the past. This membrane has about one fourth the toughness of the dura and is made up largely of fibrous tissue. The veins of Batson lie on its dorsal surface and pierce it to go ventral to this membrane and enter the vertebral body. Batson's plexus crosses the disc space. The peridural membrane extends from one side to the other, spanning the width of the vertebral body and encircling the bony canal around the outside of the dura. There is a potential space between it and the dura. It does not cross the disc space. A probe can easily be passed posterior or anterior to it, between it and the posterior longitudinal ligament or between it and the vertebral body. We also identified Hofmann's ligament anterior to the dura, attaching the dura to the posterior longitudinal ligament. Laterally, tiny attachments between this fibrovascular membrane and the circumneural sheaths of the spinal nerves can be observed as the nerves enter the foramina. The posterior longitudinal ligament (PLL) is very tough and strong and seldom ruptures. The annulus frequently ruptures. Fragments of nucleus pulposus can creep out at the vertebral rim and get under the PLL and the peridural membrane. Hematoma can form by the same route and have the exact appearance as a sequestrated disc. There is no periosteum inside the vertebral canal. With MRI, hematomas can be differentiated from an extruded fragment. They may cause symptoms similar to an extruded disc but will probably heal with time.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8367772 TI - Discography causes end plate deflection. AB - Thoracolumbar cadaver spine segments were studied by biplane radiography techniques during intradiscal injection of radiographic contrast agent. In these radiographically nondegenerated discs, significant deformation of the end plate accompanied these in vitro discograms. End plate deflections averaged 0.3 mm. The intervertebral disc bulges averaged 0.5 mm. These results suggest that the end plate itself, or events within the bone, are possible pain sources during clinical discography. PMID- 8367773 TI - Lumbar spine following successful surgical discectomy. Magnetic resonance imaging features and implications. AB - In an attempt to determine the expected long-term appearance of the lumbar spine in patients who have undergone successful lumbar discectomy, follow-up magnetic resonance (MR) examinations were performed on 23 patients (26 levels). All patients in the study had undergone at surgery at least one year prior to the study. All patients met rigorous criteria for a successful outcome. In nine cases, the postoperative study indicated a virtually total resolution of the previously identified disc herniations. In 13 cases, the study noted moderate, persistent posterior contour defects in the disc that contributed to persistent mass effect on the thecal sac or corresponding nerve root. In the remaining four cases, the postoperative study indicated virtually no change in the apparent contour of the posterior disc margin. Gadolinium contrast examinations demonstrated enhancement of the persistent contour abnormalities in 18 of 19 disc levels, suggesting the common presence of fibrosis, which was at times "mass like," in these successful patients. These findings suggest that localized discal contour abnormalities morphologically simulating recurrent disc herniations and variably contributing to mass effect, may be commonly encountered in long-term follow-up imaging studies of successful discectomy patients. PMID- 8367774 TI - Artificial disc replacement. Preliminary report with a 3-year minimum follow-up. AB - Artificial disc replacement was performed in six patients with an average age of 55 years and average follow-up of 3.4 years. Four of the six patients had juxtafusion degeneration, one had multilevel disc degeneration, and one patient had isolated disc resorption. The Acroflex disc (Acromed Corporation, Cleveland, OH), which was used in the replacement, is composed of a rubber core vulcanized to two titanium end plates. The latter have superior posts to provide for initial mechanical fixation and porous in-growth surfaces for long-term fixation. Satisfactory results occurred in four of six patients. Poor results occurred in the presence of deformity that resulted in prosthetic failure and isolated disc resorption. There was an average 8 degrees angular and 2.3-mm translational movement and satisfactory in-growth at all interfaces. Design objectives of endurance, biocompatibility, geometry, kinematics, constraint, dynamics, stability, and fail-safe were met; however, this study is preliminary in nature. PMID- 8367775 TI - Early versus late replacement of autotransfused blood in elective spinal surgery. A prospective randomized study. AB - The use of autologous blood is a well established and extremely popular technique to decrease the necessity for homologous transfusions and the attendant risks of hepatitis, HIV, and HTLV--I/II infections. The most beneficial timing for autologous reinfusion of predonated blood remains unknown. The present study was undertaken to determine the optimal timing of autologous blood reinfusion in elective spinal surgery. Fifty-seven patients were prospectively individually randomly allocated into early versus delayed reinfusion groups prior to undergoing elective spinal surgery by a single surgeon. Three surgical subgroups were entered into the study: anterior/posterior (A/P) spinal fusion patients, posterior thoracolumbar scoliosis fusion patients (PSF), and degenerative posterior lumbar fusion patients (LF). Randomization was successful in that three was no significant difference in male to female ratio, age, preoperative hemoglobin, or number of units predonated between the early and delayed reinfusion groups. Likewise, there was no significant difference in the details of the operative procedure when compared as a group for the early versus delayed reinfusion groups. A significant increase in the postoperative day #1, 2 and 3 hemoglobin was seen in the early reinfusion group, while there was no significant difference seen in the postoperative day #7 hemoglobin between the early versus delayed reinfusion group. There was no effect of surgical grouping on these significant comparisons. Earlier patient mobilization was also seen in the early reinfusion groups for the A/P and PSF groups. There was no difference in patients' subjective evaluation of satisfaction and discomfort between the early or delayed reinfusion groups as determined by blinded interview on days 1, 3, 5, and 7 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367776 TI - Deep venous thrombosis following posterior lumbar spinal surgery. AB - Postoperative duplex scans were performed on 185 patients undergoing posterior lumbar spinal surgery in order to identify deep venous thrombosis (DVT). Elastic compression stockings were used for prophylaxis in 74 patients (Group E.S.); intermittent pneumatic compression was used in the remaining 111 patients (Group P.C.). High-risk patients were not eliminated from either group. Laminectomy was performed on 84 patients (40 from Group E.S. and 44 from Group P.C.), and spinal fusion, on 101 patients (34 from Group E.S. and 67 from Group P.C.). A total of four patients, all from Group E.S., developed acute postoperative DVT. Intermittent pneumatic compression significantly reduced the incidence of acute postoperative DVT (P < 0.05). No statistically significant differences were found in the incidence of DVT in relation to the type of spinal procedure, length of procedure, duration of bed rest, or age of the patient. In conclusion, considering the low rate of DVT (2%) following posterior lumbar surgery and the potential complications of prophylactic anticoagulation, we continue to use intermittent pneumatic compression rather than elastic stockings for prophylaxis. PMID- 8367777 TI - Anesthetic effects on motor evoked potentials in dogs. AB - The effects of the various anesthetic agents on the production of transcranial magnetic motor evoked potentials (tcMMEP) were studied in a canine model. Pre anesthetic baseline tcMMEPs demonstrated consistency in onset latency measurements and variability in measurement of peak-to-peak amplitudes. Changes in tcMMEPs were evaluated following the individual administrations of sodium pentothal, etomidate, halothane, fentanyl, and ketamine. For induction of anesthesia, etomidate was compatible with tcMMEP production, whereas sodium pentothal resulted in loss of hindlimb potentials for a period of 45 minutes. For maintenance of anesthesia, halothane was incompatible with the measurement of tcMMEPs. Fentanyl administration was consistent with the recording of reliable tcMMEPs, with consistent onset latencies but widely variable peak-to-peak amplitudes. Ketamine was compatible with stable and reproducible tcMMEP production. The results of this study suggest that anesthetic agents have a predictable and consistent effect on tcMMEP responses. PMID- 8367778 TI - The effect of nerve root lesioning on various somatosensory evoked potentials in the hog. AB - Somatosensory evoked potentials (SEPs) were recorded at the lumbar spine following stimulation of the tibial nerve (mixed-nerve SEP; MSEP), the sural nerve (specific nerve SEP; SSEP), and the skin corresponding to the L6 and S1 dermatomes (dermatomal field SEP; DSEP-L and DSEP-S) in the hog. To determine the sensitivity of these three SEPs to the single nerve root (S1 root) function, the effects of nerve roots lesioning were investigated. Cutting S1 nerve root reduced the peak-to-peak amplitude of MSEP by only 28% in comparison with baseline values. The relative amplitudes of SSEP, DSEP-L, and DSEP-S were decreased by 46%, 11% and 51%, respectively. When S1 nerve root was left intact and L5, L6, and S2 nerve roots were cut, the relative amplitudes of MSEP, SSEP, DSEP-L, and DSEP-S were decreased to 68%, 73%, 31%, and 74%, respectively. These results indicate that DSEP-S is as sensitive to the function of S1 nerve root as SSEP but the sensitivities of DSEP-S and SSEP are low in the hog. MSEP is shown unsuitable to monitor the single nerve root dysfunction. PMID- 8367779 TI - Paraspinal muscle evoked cerebral potentials in patients with unilateral low back pain. AB - Cerebral somatosensory evoked potentials (SEPs) were elicited by magnetic stimulation of paraspinal muscles unilaterally at the L2 and L5 levels in 20 healthy subjects and 16 patients with low back pain and unilateral muscle spasm. A magnetic coil with a mean diameter of 4.7 cm was placed tangentially to the skin. The stimulus strength was sufficient to induce a visible muscle twitch without producing muscle contraction in the legs. The potentials recorded over the scalp consisted of several components (P30, N40, P55, N70, and P90) and were elicited in all subjects. In both healthy and patient subjects, paraspinal muscle evoked potentials were readily elicited. Vibration applied to paraspinal muscles, as well as voluntary contraction of paraspinal muscles, was associated with attenuation of the evoked potentials. This finding suggests that muscle spindle receptors provide the afferent input responsible for the early components of the magnetically evoked cerebral potentials. In patients with unilateral muscle spasm, the amplitudes of P30-N40, N40-P50, and P50-N70 were decreased significantly on the affected side when compared with values on stimulation of the unaffected side, as well as those obtained from control subjects. The cerebral evoked potentials returned to normal amplitude when the muscle spasm subsided following a period of time and after the application of spinal manipulative therapy. The technique has potential for quantitative evaluation of muscle spasm in low back pain. PMID- 8367780 TI - Predicting long-term disability in low back injured workers presenting to a spine consultant. AB - Low back pain (LBP) is the most common, costly, and disabling musculoskeletal condition. Although most LBP patients recover within two months, 2-3% eventually develop disabling chronic low back pain (DCLBP). Due to the prevalence of DCLBP problems, models have been developed to predict which acute low back pain patients are predisposed to the problems associated with this condition. Many see the development of these models as a first step that must be taken before useful approaches for containing and reducing the problem can be conceptualized, implemented, and tested. A recent publication by Cats-Baril and Frymoyer considered this specific problem. While the results of their study indicate considerable success in predicting DCLBP patients, the high prediction rates they obtained may be spurious because of the characteristics of their sampled patient population in conjunction with some of the predictors they found useful in identifying DCLBP patients. The purpose of the present study was to focus on the crucial patient population (i.e., acute LBP patients who perceive their problem as work-related and who have been unable to work for more than two but less than six weeks), and evaluate the ability of various personal, medical, occupational, and psychological factors to predict predisposition to DCLBP. Fifty-five patients referred by occupational physicians were evaluated and followed successfully for at least 6 months. Patients in the study were given a physical examination that included Spratt et al's assessment of pain behavior. They were then asked to fill out an extensive battery of self-report questionnaires, addressing issues associated with personal demographics, health history, work requirements, job satisfaction, injury information, and pain/function factors. At the 6-month follow-up, a structured telephone interview was used to obtain outcome information regarding patient status, including ability to return to work and general outcomes of treatment. Average patient age was 37.2 years (range, 22-57) and 67% of the patients were male. On average, patients had been unable to work for approximately 4 weeks when initially surveyed. Overall, 12.7% of the patients returned to work within 1 month of injury, 40% returned within 2 months, 54.5% within 3 months, 69% within 4 months, 74.5% within 5 months, 76.3% within 6 months, 80% within 7 months, and 83.6% after 7 months. Approximately 16% never successfully returned to work within the follow-up period of this study. DCLBP was found to be correlated only with marital status, as married patients returned to work more quickly than single patients (P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8367781 TI - Responding to the pressures on spine. PMID- 8367782 TI - Interference screw fixation of cervical grafts. A combined in vitro biomechanical and in vivo animal study. AB - The dislodgement of an anterior bone graft in the cervical spine is a frequent complication of attempted fusion following discectomy or corpectomy. It has been hypothesized that fixation augmented with interference screws may increase the pullout strength of the construct and decrease the rate of these complications. In vitro mechanical tests and in vivo sheep studies were conducted to compare interference screw fixation methods for enhancing the fixation between the bone graft and the adjacent vertebra. Using human cadaver cervical spines, the anterior pullout strengths of cervical bone grafts were compared using fixation with and without the addition of interference screws for the in vitro mechanical testing. The mean pullout forces for a Smith-Robinson type bone graft alone was 58.1 N (SD 11.4 N); for the graft augmented with two 3.5 mm cancellous bone screws, 153.9 N (58.9 N); and for the graft with four 3.5 mm screws, 217.1 N (SD 69.9 N). The pullout strengths of the two- and four-3.5 mm screw constructs were significantly greater than the strength of the graft alone (P < 0.05). Similarly placed 2.7 mm cortical screws of the same length provided increased pullout strength (123.7 N 38.6 N and 142.5 N 38.2 N for two- and four-screw constructs, respectively); however, in comparison to the graft alone, these differences were not statistically significant. For both screw types, the four-screw fixations were stronger than the two-screw fixations, although these differences were not statistically significant. For the in vivo portion of the study, a single-level anterior cervical discectomy and fusion were performed on 20 sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367783 TI - Thoracolumbar burst fractures. The clinical efficacy and outcome of nonoperative management. AB - There continues to be considerable controversy regarding the management of thoracolumbar burst fractures. Most feel that failure of the middle osteoligamentous complex, particularly with retropulsion of fragments into the spinal canal, is an indication for operative management. Others advocate postural reduction and prolonged bedrest for such injuries. The purpose of this study was to 1) review the clinical outcome and efficacy of closed management of thoracolumbar burst fractures; and 2) quantify what, if any, remodeling occurs in the bony canal as measured by serial CT. Forty-one patients who presented with a burst fracture of the thoracolumbar spine without neurologic deficit were reviewed clinically and radiographically following nonoperative management. At injury, canal compromise averaged 37% (range, 16-66%); 26 patients had at least 30% canal compromise. During treatment, one patient developed neurologic deterioration that prompted surgery; all other patients remained neurologically intact. At average follow-up of 2 years, an overall outcome evaluation indicated that 49% of the patients had excellent outcomes relative to pain and function; 17%, good; 22%, fair; and 12%, poor. Approximately 90% of the patients had a satisfactory work status relative to factors associated with their burst fracture. Serial roentgenograms documented significant progression in body collapse, which averaged 8% (P < 0.0001) from injury to follow-up. On the other hand, serial CTs documented significant improvement from injury to follow-up for canal compromise and midsagittal diameter. Average improvements in canal compromise and midsagittal diameter were 22% (P < 0.0001) and 11% (P < 0.0001), respectively. Only three patients had canal compromise greater than 30%, no patients had canal compromise greater than 40%, and no patients experienced canal area deterioration over time. On average, nearly two-thirds of the fragment occluding the canal resorbed, with most remodeling complete within one year. For patients with burst fractures presenting neurologically intact, we obtained the following findings: 1) nonoperative management yields acceptable results; 2) following nonoperative management, bony deformity (i.e., kyphosis and body collapse) progresses marginally relative to the rate of canal area remodeling; 3) incidence of subsequent neurologic deficits is quite low; and 4) initial radiographic severity of injury or residual deformity following closed management does not correlate with symptoms at follow-up. This pattern of results suggests nonoperative management as the preferred treatment in these circumstances. PMID- 8367784 TI - Nonoperative management of stable thoracolumbar burst fractures with early ambulation and bracing. AB - Eighteen neurologically intact patients with burst fractures at the thoracolumbar junction were treated with early ambulation in a total contact orthosis. No attempt was made to reduce the associated deformity. Selection criteria excluded patients with posterior column disruption. Hospital stay averaged 10 days. Follow up averaged 19 months. Mean kyphosis was 19 at time of injury and 20 at follow up. At follow-up, 15 patients rated their pain as little or none. Seventeen patients had little or no restriction of activity. Follow-up computed tomography (CT) scans obtained in eight patients showed significant resorption of retropulsed bone. No deterioration of neurologic function developed in any patient. In patients with intact posterior elements and thoracolumbar burst fractures, early mobilization in a total contact TLSO can lead to satisfactory functional results. Prolonged bed rest was not required in this series. The authors attribute the good results of nonoperative management to the exclusion of patients with posterior column disruption. PMID- 8367785 TI - Biomechanical analysis of three surgical approaches for lumbar burst fractures using short-segment instrumentation. AB - Burst fractures of the lumbar spine that are located below the thoracolumbar junction present a challenge when operative management is indicated. Short segment instrumentation offers the advantage of incorporating fewer motion segments in the fusion, but may not provide adequate long-term stabilization. The goal of this study was to assess the axial stiffness and torsional rigidity of several short-segment instrumentation procedures. Compressive axial stiffness and torsional rigidity were measured in six intact porcine lumbar spines (L1-L5). A corpectomy was performed to simulate a burst fracture injury and decompression. Posterior instrumentation, posterior instrumentation with an anterior strut (a wood block), and anterior instrumentation with an anterior strut one level above and one level below the fracture site were applied as treatment strategies. VSP plates (Acromed, Cleveland, OH) for posterior instrumentation and the Kaneda system (Acromed, Cleveland, OH) for anterior instrumentation were used. Load displacement and torque-angle plots were generated and used to calculate 144 estimates of axial stiffness and 144 estimates of torsional rigidity for these constructs. These analyses showed that, in comparison with the intact spine, posterior instrumentation alone was an average of 76% less stiff axially, posterior instrumentation with an anterior strut was 3% more stiff (not significantly different from intact), and anterior instrumentation with an anterior strut was 15% more stiff. Posterior instrumentation alone was an average of 30% less rigid in torsion, posterior instrumentation with an anterior strut was 26% less rigid, and anterior instrumentation with an anterior strut was 24% less rigid than the intact spine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367786 TI - A prospective, randomized study of lumbar fusion. Preliminary results. AB - One hundred, twenty-four patients undergoing lumbar or lumbosacral fusion for degenerative conditions were entered into a prospective study. The patients were randomly assigned to one of three treatment groups. Group I underwent posterolateral fusion using autogenous bone graft. Group II had autogenous posterolateral fusions supplemented by a semi-rigid pedicle screw/plate fixation system (Luque II; Danek Medical, Memphis, Tennessee). Group III patients underwent posterolateral autogenous fusion with a rigid pedicle screw/rod fixation system (Texas Scottish Rite Hospital [TSRH]-Danek Medical, Memphis, Tennessee). All the patients were operated on by the same surgeon, identical bone grafting technique was used in all, and all were treated in an identical fashion postoperatively. Fusion status was determined from the anteroposterior, oblique, and flexion-extension radiographs obtained at 1 year. Clinical results were rated as excellent if the patients were pain-free and had returned to work; good if the patients had mild backache requiring non-narcotic analgesics and had returned to work; fair if continuing back pain prevented a return to work; or poor if the pain was worse than that which the patient experienced preoperatively or the patient required revision surgery. Nine patients who were originally assigned to Group II or Group III were placed in Group I intraoperatively. This change was due to the identification of severe osteopenia and the determination that pedicle screw purchase was poor. One patient was lost to follow-up. Thus, 51 patients were in Group I, 35 in Group II, and 37 in Group III. Follow-up ranged from 9 to 28 months, averaging 16 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367787 TI - Straight leg raising. Anatomical effects on the spinal nerve root without and with fusion. AB - Straight leg raising (SLR) is a useful clinical test to demonstrate an inflammatory compressive process across a spinal nerve root. Several previous studies have attempted to evaluate the effect of SLR on nerve root motion, but the exact direction and amount of this motion is still unclear. Components of the SLR test that have not been adequately addressed include the effect of SLR on the intact dural-nerve root system, motion of the nerve tissues as distinct from the dura, and nerve root strain. Separately, spinal fusion is occasionally used as an adjunct to discectomy to decrease instability and subsequent "nerve root irritation." The effect of a one-level fusion on in situ nerve root biomechanics, however, has not been evaluated. Ten fresh human cadavers underwent posterior lumbar laminectomies. Spinal nerve root motion was studied while a SLR maneuver was performed. Data was recorded photographically and statistically analyzed. The results were as follows: 1) SLR induced both linear motion (0.5-5 mm) and strain (2-4%) in spinal nerves L4, L5, and S1; 2) The dura moved less than the intrathecal nerve root at the pedicle and experienced more strain (P < .05). 3) The nerve roots moved laterally toward the pedicle and thus would move into a posterolaterally herniated disc. 4) Rigid anterior stabilization did not decrease nerve root motion or strain. PMID- 8367788 TI - Arterial vascularisation of the extrahepatic biliary tract. AB - The aim of this study was to establish a plan of the arterial distribution to the main supraduodenal biliary tract in order to draw practical conclusions for biliary surgery, especially in bilio-alimentary and bilio-biliary anastomoses and liver transplantation. It was based on a study of 60 fresh subjects and was carried out using four different methods: dissection after injection of colored latex into the superior mesenteric a. (10 subjects), radiography and dissection after injection of Micropaque into the celiac trunk (10), dissection after injection of Indian ink into the common hepatic a. (10) and radiography and dissection after selective injection of the right hepatic a. or the gastroduodenal a. (30). Analysis of the results leads to definition of three types of vascularisation and two territories, superior and inferior, overlapping at the level of the mouth of the cystic duct. The practical implications for biliary surgery and liver transplantation are discussed. PMID- 8367789 TI - The relationship between Meckel's cartilage and the development of the human fetal mandible. AB - This work studied the development of the ventral part of Meckel's cartilage and its relationship to the morphogenesis of the mandible in a series of human fetuses. The development of the cartilage was followed up to the end of the embryonic period (stage 23, 8th week) when the primary ossification centre, which was formed from a condensation of embryonic mesenchyme, had become two bony plates forming a trough in which lay the neurovascular bundle. From this trough invagination of the bony plate formed the dental crypt. The primary ossification centre disappeared around the sixth month of fetal life. PMID- 8367790 TI - Evaluation by angiography of the lateral dominance of the drainage of the dural venous sinuses. AB - Venous drainage dominance of the dural venous sinuses may be defined as the drainage only or mainly into one of the transverse sinuses, as shown by bilateral carotid angiography. The aim of this study was to evaluate the venous drainage dominance in bilateral carotid angiograms of 189 cases retrospectively. Among these cases 41.3% showed drainage mainly to the right side, 37.6% showed equal drainage to each side, 18.5% showed drainage mainly to the left side, 2.1% showed drainage only to the right side and 0.53% showed drainage only to the left side. Cerebral venous drainage dominance is of great importance and should be considered before operations on patients for radical neck dissection, removal of tumors in the neck that invade the internal jugular vein or tumors of the glomus jugulare which may require ligation of the internal jugular vein. PMID- 8367791 TI - Epiphysial ossification centres in iliosacral joints: anatomy and computed tomography. AB - Bilateral apparently bony structures of different forms and sizes located in the inferior and superior ventral parts of the sacroiliac joints were observed on axial CT images of the pelvic region of juvenile patients. No other pathological changes were noted in the sacroiliac joints of these individuals. In one patient the bony structures could also be seen on a conventional plain radiograph. We also examined 3 juvenile autopsy specimens of this joint using radiology, CT, macroscopical evaluation and histology. In two of them, structures could be detected on the CT scans which were similar to those observed in the young patients. Macroscopic investigations revealed the structures to be secondary ossification centres located in the articular cartilage of the lateral part of the os sacrum at the levels of the first and third sacral segments. According to older anatomical literature, these epiphysial ossification centres contribute to the auricular surface of the lateral part of the os sacrum and the free lateral surface of the inferior sacral parts. They can be observed between the ages of 12 and 25 years and begin to synostose with the lateral part around the age of 18 years. In macerated juvenile specimens of the bony pelvis, free ossicles were not detectable in the region of the sacroiliac joints. Histological peculiarities of the ossification process observed are discussed. These physiologically occurring ossification centres are to be differentiated from pathological alterations appearing as bony or bone-like structures on CT scans. PMID- 8367792 TI - Sonographic quantitative analysis of the heart in the third trimester of gestation. AB - The fetal heart was studied with transabdominal sonography in 40 single normal pregnancies to analyze the increase of cardiac length and width (major longitudinal and transverse diameters of the heart) during the third trimester. Relationships between the cardiac data and fetal age, femur length and biparietal diameter (BPD) were explored by allometry and linear regression analysis. The length and width of the heart could be measured reproducibly in the 4-chamber view of the heart. This study verified that the heart grows very rapidly during the third trimester (positive allometry). The linear increase of the fetal heart shows a strong and significant correlation with the increase of both femur length and BPD. This suggests that non invasive analysis of cardiac data can be useful for prenatal detection of congenital heart disease or for the assessment of gestational age. PMID- 8367794 TI - Left superior vena cava continuing to the accessory hemiazygos without anastomosis with the coronary sinus. AB - A case of double superior vena cava lacking the left brachiocephalic vein was found. The left superior vena cava directly continued to the accessory hemiazygos vein without anastomosis with the coronary sinus. Therefore, the blood from the left superior vena cava drained into the right superior vena cava via the transverse anastomosis between the left and right azygos lines. It was thought that embryologically 1) the inter-precardinal vein was not formed, and 2) the left precardinal vein did not continue to the common cardinal vein, rather it drained into the left azygos line. This case may represent one of the most basic arrangements of the superior caval system. PMID- 8367793 TI - Static morphometric bases for CT identification and evaluation of the outflow chamber of the left ventricle. Preliminary study in formalin-fixed heart. AB - A static morphometric study of the outflow chamber of the left ventricle (OCLV) was investigated in a series of 10 formalin-fixed hearts. A spatial reconstruction of the shape and the volume of the OCLV was carried out by means of a Somaton Plus TR4 Tomodensitometer (Siemens). The technic allows evaluation of the surface of the aortic and the mitral orifices and visualization of the three-dimensional OCLV and LV morphology, as well as calculation of their volumes. The limits of the technic in the dynamic study of the OCLV are presented. PMID- 8367795 TI - One further case of unusual origin of three hepatic arteries. AB - This article describes a triple vascularization of the liver which is not a common vascular anomaly. Dealing with this particular kind of vascularization, we note the following: a main hepatic a. which enters in the right lobe of the liver and two accessory arteries, the right hepatic a. (a branch of the superior mesenteric a.) and left hepatic a. (from the left gastric a.). In the same way, the cystic a. has an unusual origin: the right accessory hepatic artery. The whole hepatic pedicle was dissected, and its branches were described, indicating their relations, length and diameter. PMID- 8367796 TI - The iceman. PMID- 8367797 TI - Anterolateral thoracic fascia: an anatomic and surgical entity. AB - This anatomic study, based on six subjects, is aimed at a better description of the anterolateral thoracic fascia, not previously studied in its entirety. The literature describes a fascia of the pectoralis major m. continuous with that of the serratus anterior m., starting at the lateral border of the pectoralis major or pre-pectoral. The upper limits have never been studied and the lower limits are ill-defined, the aponeurosis of the pectoralis major or the pre-pectoral fascia being continuous with that of the rectus abdominis m. It is shown that this fascia, from a retropectoral origin, extends to the base of the axilla above and is stretched as bridge between the pectoralis major and latissimus dorsi mm. and the muscles of the anterolateral wall of the abdomen. This fascia has some surgical importance as a plane of coverage in the protection of mammary implants. The lack of concordance with classical anatomic accounts, the histology and the vascularisation of this fascia call for complementary studies. PMID- 8367798 TI - A study of the orientation of the fibers of the flexor carpi radialis tendon: anatomy and clinical applications. AB - The authors report a series of 41 dissections of the forearm intended to study the orientation of the fibers of the flexor carpi radialis (FCR). This shows that there is a constant torsion of the fibers of the FCR by an average of 180 degrees. Half of this torsion occurs in the forearm and half in the sheath of the FCR at wrist level. Awareness of this torsion is particularly useful surgically when the tendon is employed in ligamentoplasty, particularly after trapeziectomy. Our study of the orientation of the fibers was aimed at the ability to perform subcutaneous splitting of the fibers for use of part of the tendon. PMID- 8367799 TI - Segmentary analysis of the coronary artery distribution in the left ventricle. AB - In a series of 90 human hearts, from individuals aged between 4 days and 94 years (X = 61.09 +/- 21.96) the coronary arterial distribution of the left ventricle (LV) was studied using Selvester's system of segmentation[24]. Postmortem angiographies and microdissection techniques were used. The analysis of the 12 segments of the LV showed that the three septal segments (basal, mesial and apical) present a type of irrigation which is practically constant and of a dual type. The superoapical, posterobasal and posteromesial segments present an irrigation with a high index of exclusivity for the anterior interventricular and circumflex arteries. In the rest of the segments the vascularization is of a mixed type, although the apical segments reach an important degree of arterial exclusivity. The analysis by segments of the LV allows us to conclude that the arterial vascularization of the left ventricle depends fundamentally on the anterior interventricular artery and the left circumflex artery, which are those that present the greatest extension, together with a small contribution by the right coronary artery, which is always minor with respect to the left coronary artery. PMID- 8367801 TI - Acute mesenteric ischemia. AB - Acute mesenteric ischemia resulting from specific etiologies is a treatable vascular emergency. It requires a high index of suspicion and prompt, aggressive resuscitation and diagnostic maneuvers to determine the specific underlying cause. This will allow specific directed surgical revascularization, optimization of cardiac performance, or correction of a hypercoagulable state, all directed at maximizing the amount of functional bowel that is salvageable. These strategies are the cornerstones for a successful outcome in this life-threatening vascular catastrophe. PMID- 8367800 TI - Anatomical observations of spurs of the tuber ischiadicum. AB - In a study of 101 human pelves, 8 pelves (only males) were found with ossification in the area of the ligamentum sacrotuberale. Seven of these showed a characteristic and similar morphology and could be considered to be periosteal exostoses. The term "spur of the tuber ischiadicum" is proposed for this manifestation. There was a single case of metaplastic ossification, possibly of traumatic origin. Hence, not all ossifications in the area of the ligamentum sacrotuberale can summarily be classified as a spur of the tuber ischiadicum; careful discrimination is essential in every case. PMID- 8367802 TI - Medullary carcinoma of the thyroid--therapeutic strategy derived from fifteen years of experience. AB - BACKGROUND: The purpose of this investigation was to analyze our experience with patients treated for medullary carcinoma of the thyroid to identify prognostic factors and to develop a stage-related treatment strategy that might improve cure rates. METHODS: Between 1970 and 1985 a total of 40 patients with medullary thyroid carcinoma were treated (21 women, 19 men; mean age +/- SEM; 40 +/- 3 years; mean follow-up, 82 +/- 12 months). Initial operation involved total thyroidectomy (28 patients), subtotal resection (11 patients), and a lobectomy (1 patient). The initial lymph node dissection generally consisted of a selective removal of enlarged nodes. Unilateral neck dissection was performed in six cases. Secondary operation for recurrent disease was necessary in 26 patients. RESULTS: At the end of the follow-up period 10 patients were tumor free, 12 patients were scheduled for further treatment, six patients suffered from persistent but clinically occult disease, and 12 patients had died (mean survival time, 68 +/- 7 months). The paramount prognostic factor was the absence or presence of lymph node involvement at the time of primary operation (p = 0.011). Patients with distant metastases died within 2 years of diagnosis. Women, patients younger than 40 years of age, and those elicited by familial screening programs exhibited increased survival times. CONCLUSIONS: Because of the prognostic and therapeutic importance we recommend the total thyroidectomy with a complete dissection of the central lymph node compartment as primary treatment. Patients with lymph node involvement or elevated serum calcitonin levels should subsequently be treated by a modified radical neck dissection of the lateral compartments. PMID- 8367803 TI - Management of obstructing lesions of the left colon by resection, on-table lavage, and primary anastomosis. AB - BACKGROUND: The purpose of this study was to assess the feasibility and safety of single-stage resection, on-table lavage, and primary anastomosis in patients presenting with obstruction of the left colon. METHODS: The outcome of surgery in 73 consecutive patients presenting with obstruction of the left colon during a 5 year period was assessed in terms of perioperative complications and long-term survival. RESULTS: Sixty-three patients (86%) underwent single-stage restorative procedures. In this group there were four clinical anastomotic leaks (6%). However, there were no deaths as a result of leakage. There were four deaths (6%) but these were not due to anastomotic leakage. Long-term survival rates compared favorably, stage for stage, with large published series of elective experience. CONCLUSIONS: We believe that resection, on-table lavage, and primary anastomosis constitute the operation of choice for most patients with acute obstruction of the left colon. PMID- 8367804 TI - Ultrasonography in the initial evaluation and follow-up of blunt abdominal injury. AB - BACKGROUND: Ultrasonography has been routinely performed in the assessment of blunt abdominal injury at our department of surgery since 1980. To establish its reliability, a retrospective study was carried out on 818 consecutive patients in the years 1980 to 1990. METHODS: Seven hundred twenty six patients underwent real time ultrasonographic examination of the abdomen. Indication for ultrasonography included all cases evaluated for blunt abdominal trauma. Ninety two patients before 1985 were excluded. RESULTS: Two hundred seventy (37.2%) patients underwent laparotomy, 252 patients (34.7%) because of ultrasonographic diagnosis. Celiotomy was nontherapeutic in 28 patients; 26 of these patients had positive findings from ultrasonography (false positive, 3.6%). Eighteen patients with negative findings from ultrasonography also underwent laparotomy, which was nontherapeutic in two patients (false negative, 2.2%). Four hundred fifty six patients (62.8%) were managed without operation, relying on initial and follow-up ultrasonography, which was negative in 386 (53.2%) and positive in 70 patients (9.6%). The accuracy of ultrasonography was 94.2%, with 91.9% sensitivity, 96.0% specificity, and 94.9% predictive value. The rate of delayed recognition of documented visceral injury was 5.1%, but no false-negative findings from ultrasonography were noted among these patients. CONCLUSIONS: Ultrasonography has proved to be a thoroughly reliable, cost efficient, and noninvasive modality in primary evaluation and follow-up of blunt abdominal trauma. PMID- 8367805 TI - Prognosis in esophageal carcinoma with cervical lymph node metastases. AB - BACKGROUND: The purpose of this study was to assess cervical lymph node (C-LN) metastases and to examine whether the site of the C-LN metastasis impacts on survival of the patient with thoracic esophageal cancer. METHODS: Transthoracic esophagectomy and three-field dissection (mediastinal, abdominal, and C-LN) followed by esophageal reconstruction were performed on 68 patients with squamous cell carcinoma of the thoracic esophagus who were seen at our institution from 1983 to 1990. RESULTS: C-LN metastasis was seen in 20 (29.4%) patients, and the survival curve of the 20 patients with positive C-LN metastasis was not significantly different from that of the 48 patients without positive C-LN metastasis. The survival curve of patients (n = 7) with positive node limited to recurrent laryngeal nerve chain node (RLN group) was significantly better than that of patients (n = 13) with positive internal jugular nodes including supraclavicular nodes (IJN group) (p = 0.010; generalized Wilcoxon). This was because there were more patients in the IJN group (84.6%) than in the RLN group (28.6%) (p = 0.022) who had five or more positive nodes in the three fields. CONCLUSIONS: The results suggest that RLN should not be defined as M1 but as N1 in thoracic esophageal cancer. PMID- 8367806 TI - Factors predicting chronic hepatic encephalopathy after distal splenorenal shunt: a multivariate analysis of clinical and hemodynamic variables. AB - BACKGROUND: This study was aimed at evaluating several factors that promote chronic hepatic encephalopathy by multivariate analysis of data for patients with cirrhosis with good or moderate liver function submitted to distal splenorenal shunts. METHODS: The study group comprised 131 patients: 55 had alcoholic and 76 nonalcoholic cirrhosis. Seventy patients were in Child's class A and 61 in class B. Cerebral function was assessed by a complete neurologic examination. Angiography with venous phase was performed before and within 1 month after the shunt operation. In 84 cases the original Warren technique was used and in 20 cases a Britton's modified procedure was used. Twenty-seven patients had distal splenorenal shunts with a splenopancreatic disconnection. Statistical analysis was performed by two multivariate analyses based on stepwise selection. RESULTS: Thirty-nine patients died during a follow-up period of 51 +/- 32 months. Chronic encephalopathy occurred in 18 patients (14%). According to the multivariate analysis of the preoperative prognostic factors, only age (p = 0.0001) and albumin values (p = 0.0002) were independent predictive risk factors for chronic encephalopathy. In the multivariate analysis concerning the hemodynamic consequences of the selective shunts, independent risk factors promoting chronic encephalopathy were postoperative portal perfusion (p = 0.0001), postshunt portal pressure (p = 0.001), and surgical disconnection (p = 0.0064). CONCLUSIONS: Our study has shown that chronic encephalopathy after selective shunt surgery is promoted by both clinical and hemodynamic factors. A better selection of the candidates for shunt surgery and prevention of the development of portal malcirculation by accurate surgical disconnection should further decrease the risk of chronic encephalopathy. PMID- 8367807 TI - Cervical vascular injuries: a trauma center experience. AB - BACKGROUND: We analyzed 76 patients with cervical vascular injuries from penetrating neck trauma (n = 528) between 1977 and 1990 at a level I trauma center to evaluate the role of angiography in diagnosis and management and to assess the course and outcome of these patients. METHODS: Patients who were hemodynamically unstable underwent immediate surgical exploration. Stable patients were subjected to diagnostic investigation. Angiography was routinely performed to diagnose vascular injury in zones I and III and zone II if the trajectory was in the vicinity of major vessels. Therapeutic embolization was performed when possible at angiography; all other vascular injuries were treated surgically. RESULTS: Thirteen patients (2.5%) died of penetrating neck trauma, in 12 of whom hemorrhage was the contributing factor (12/76; 15.8% of patients with vascular injury). In nine patients who were hemodynamically stable vascular injury was diagnosed by angiography: 5 (6.8%) of 73 in zone I and 3 (5.4%) of 56 in zone III, four of whom underwent therapeutic embolic occlusion of the injured vessel. Injuries to vertebral and subclavian arteries and subclavian and innominate veins were often multiple, causing exsanguination and death (6.8% in zone I). In three patients with no preoperative neurologic deficit, the internal carotid artery was ligated without complication; in all other patients injury to the common carotid or internal carotid artery was repaired, in six of them with polytetrafluoroethylene grafts. CONCLUSIONS: Selective management of penetrating neck trauma should include routine angiography in zones I and III. Injuries to the common and internal carotid arteries should be repaired. The internal carotid artery may be ligated in the absence of preoperative neurologic deficit. Arterial injuries in the neck can be repaired with polytetrafluoroethylene grafts. PMID- 8367808 TI - Postoperative gastroparesis and tachygastria--response to electric stimulation and erythromycin. AB - BACKGROUND: The purpose of this study was to correlate clinical course, gastric emptying, and gastric myoelectric activity in a patient after gastric operation and to determine the effect of electric stimulation and the administration of erythromycin on the patient's gastric rhythm. METHODS: Daily myoelectric recordings were obtained through implanted gastric electrodes after truncal vagotomy and gastroenterostomy for an obstructing duodenal ulcer. RESULTS: The patient had acute postoperative delayed gastric emptying, accompanied initially by stomal edema but subsequently associated with persistent tachygastria. The gastric rhythm was only transiently slowed by multiple attempts at electroversion but appeared to respond dramatically to intravenous erythromycin therapy. Although delayed gastric emptying persisted on radionuclide gastric emptying studies, the patient slowly improved clinically with continued erythromycin therapy. CONCLUSIONS: Disturbances in gastric rhythm may accompany postoperative gastroparesis, although in our patient the dysrhythmias appeared to occur secondary to gastric outlet obstruction. Although his stomach could be paced, pacing was not effective in restoring a normal gastric rhythm. In contrast, intravenous erythromycin therapy was associated with rapid restoration of a normal gastric rhythm and slow improvement in gastric function. PMID- 8367809 TI - The effect of erythromycin on motility of the duodenum, sphincter of Oddi, and gallbladder in the prairie dog. AB - BACKGROUND: Interdigestive motility of the stomach, duodenum, sphincter of Oddi, and gallbladder is mediated through the migrating myoelectric complex and the action of motilin. Erythromycin, a motilin agonist, has recently been studied as a gastrointestinal and biliary prokinetic agent. We hypothesized that erythromycin would increase interdigestive duodenal and sphincter of Oddi motility in a dose-dependent manner. METHODS: In 10 anesthetized prairie dogs we determined the motility responses of the duodenum, sphincter of Oddi, and gallbladder to erythromycin infusion during a three-log dosing regimen and correlated activity with serum concentrations of the drug. RESULTS: Erythromycin administered at 0.01 and 0.1 mg/kg had no effect on duodenal or sphincter motility. At 1.0 and 10 mg/kg, duodenal motility index increased by 451% +/- 114% and 1070% +/- 480%, respectively, when compared with baseline values, (p < 0.05). Sphincter of Oddi motility index increased by 122% +/- 38% and 323% +/- 99%, respectively, at these same doses of erythromycin (p < 0.05). Gallbladder pressure did not change significantly during erythromycin infusion. Erythromycin serum concentration at 1.0 mg/kg was 1.0 +/- 0.7 micrograms/ml. CONCLUSIONS: These data suggest that erythromycin stimulates interdigestive motility of the duodenum and sphincter of Oddi in a dose-dependent manner at otherwise subtherapeutic concentrations of the drug. PMID- 8367810 TI - Safe intraabdominal pressure of carbon dioxide pneumoperitoneum during laparoscopic surgery. AB - BACKGROUND: The deliberate induction of carbon dioxide pneumoperitoneum during laparoscopic surgery could be a possible source of cardiovascular collapse. The effects of elevated intraabdominal pressure (IAP) on systemic hemodynamics and splanchnic blood flow created by insufflation of carbon dioxide were examined in anesthetized dogs. METHODS: Stepwise increases in IAP of 8 (n = 7), 12 (n = 7), and 16 (n = 7) mm Hg were applied to determine the threshold pressure that had minimum influence on these hemodynamics. Hemodynamic parameters were measured at baseline and 1, 2, and 3 hours after the start of insufflation. RESULTS: At an IAP of 16 mm Hg, cardiac output was decreased significantly by 1 hour after the start of insufflation and became progressively lower during the procedure. Systemic vascular resistance was elevated significantly in parallel with the change in cardiac output. Although hepatic arterial blood flow was not decreased significantly, portal venous and superior mesenteric arterial blood flows were diminished significantly at 16 mm Hg, resulting in a decrease in total hepatic blood flow. No significant changes were observed in these parameters at 8 or 12 mm Hg. CONCLUSIONS: Based on these results, an IAP from 8 to 12 mm Hg is recommended for laparoscopic surgery, to avoid complications caused by hemodynamic derangements. PMID- 8367811 TI - Role of contralateral breast biopsy in infiltrating lobular cancer. AB - BACKGROUND: Although infiltrating lobular carcinoma (ILC) is known to be associated with higher rates of bilaterality, contralateral breast biopsies are not routinely performed in such patients. METHODS: The pathology reports of all patients with ILC admitted to Memorial Sloan-Kettering Cancer Center between 1970 and 1980 were retrospectively reviewed. The incidence of contralateral biopsies, random and directed, was determined. The findings on contralateral biopsy were evaluated with respect to age of the patient, nodal status of the ipsilateral cancer, and multicentricity of the primary lesion. RESULTS: Of the 275 patients undergoing mastectomy for ILC, 130 (47%) had contralateral biopsies. Twenty-two were directed biopsies and 108 were random biopsies. On random biopsy 11 (10%) patients were found to have infiltrating carcinomas and seven (6%) were found to have intraductal cancer. Multicentric invasive disease in the ipsilateral breast was found to be predictive of a positive contralateral biopsy (p = 0.01). CONCLUSIONS: Despite the current trend toward less extensive surgery for breast cancer, random contralateral breast biopsy is indicated in patients with ILC. PMID- 8367812 TI - Edwin Hartley Pratt and orificial surgery: unorthodox surgical practice in nineteenth century United States. AB - Among the more interesting yet bizarre chapters in the history of nineteenth century American medicine was the emergence of "orificial surgery" as a widely practiced specialty. This philosophy, the treatment of chronic disease through surgical operations on the rectum, vagina, cervix, urethra, nares, and mouth, evolved from the personal practice experiences of Edwin Hartley Pratt, a homeopathic general practitioner/surgeon. Through his salesmanship skills, Pratt was able to establish a field of surgery that maintained its own national society, in addition to publishing a widely distributed specialty journal. PMID- 8367813 TI - The effect of acute nonbacterial dependent peritonitis on lung and liver oxidant stress and antioxidant activity. AB - BACKGROUND: The role of oxidant release and tissue antioxidant defenses on inflammation-induced organ injury is not clearly defined. METHODS: We determined the effect of acute zymosan peritonitis in rats on lung and liver tissue oxidant stress and antioxidant defenses during a 5-day period. Oxidant activity was measured as tissue malondialdehyde and oxidized glutathione (GSSG). Antioxidant activity was measured as tissue-reduced glutathione (GSH) and catalase activity. Rats were maintained hydrated with subcutaneous crystalloid. Animals were killed at 4, 12, and 24 hours and 5 days. RESULTS: Acute peritonitis was evident at 12 and 24 hours but was resolving at 5 days. Peritoneal fluid cultures were negative after 24 hours. A 50% mortality rate was noted between 20 and 30 hours, with no deaths after 30 hours. We noted a significant increase in lung GSSG and malondialdehyde at 4 hours that persisted for the 5 days, as did histologic evidence of a progressing severe lung inflammation. No increased conversion of lung xanthine dehydrogenase to xanthine oxidase was noted. Lung GSH and catalase activity were maintained at control despite negligible food intake. In contrast, liver GSSG was increased significantly only at the 4-hour period, corresponding with a transient conversion of xanthine dehydrogenase to xanthine oxidase from 10% to 31%. Tissue malondialdehyde did not increase despite the initial oxidant stress. However, tissue GSH and catalase values decreased by more than 50% after 24 hours and remained decreased at 5 days. CONCLUSIONS: We conclude that early lung and liver oxidant stress is initiated by acute peritonitis. Lung oxidant changes persist and lung dysfunction progresses, even though antioxidant activity is maintained and acute peritonitis is resolving. Liver lipid peroxidation did not develop despite oxidant release, probably because of a large antioxidant reserve. However, a severe and sustained decrease in liver antioxidants results, increasing the potential damage from a subsequent oxidant insult. PMID- 8367814 TI - Reduction of systemic drug exposure after hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration. AB - BACKGROUND: Hepatic arterial infusion of doxorubicin has produced tumor response in hepatic malignancies; however, the limited success of these treatments is related in part to dose-limiting systemic toxicities. The purpose of this study was to determine whether a novel venous isolation-chemofiltration system could limit systemic exposure to doxorubicin after hepatic arterial infusion. METHODS: Doxorubicin (1 or 3 mg/kg) was infused in the hepatic arteries of domestic pigs after complete hepatic venous isolation was achieved with a dual-balloon vena cava catheter. The hepatic vein effluent was pumped through an extracorporeal carbon chemofiltration circuit. Doxorubicin levels were measured in prefilter (hepatic vein), postfilter, and systemic serum at intervals up to 1 hour after drug infusion. RESULTS: Complete hepatic venous isolation with extracorporeal chemofiltration significantly reduced (> 90%) the postfilter and systemic levels of doxorubicin compared with prefilter levels (p < 0.01). At the time animals were killed 7 days after infusion of doxorubicin (3 mg/kg), tissue levels of doxorubicin in the liver showed a 16-fold increase compared with levels in the heart (p < 0.01). CONCLUSIONS: For chemotherapeutic drugs like doxorubicin with a low first-pass extraction by the liver, the novel system described herein achieved significant reduction in systemic drug exposure. This system will allow dose intensification of doxorubicin administered by hepatic arterial infusion to treat hepatic malignancies. PMID- 8367816 TI - Thermal injury-induced changes in the rat intestine brush border cytoskeleton. AB - BACKGROUND: The brush border cytoskeleton maintains the selective absorptive surface of the intestine epithelium. Increased intestinal permeability caused by cutaneous thermal injury may be the result of changes in the organization of the brush border cytoskeleton. METHODS: In this study we used electron and laser confocal microscopy to examine the temporal and spatial organization of the rat brush border cytoskeleton after thermal injury. RESULTS: Vesiculation of microvilli and disruption of core actin filament bundles were observed in rats with burns covering 20% total body surface area (TBSA). In rats with 40% TBSA burns changes in the brush border cytoskeleton were more pronounced, resulting in increased vesiculation of microvilli and disruption of terminal web actin filaments. Confocal microscopy of corresponding areas of the gut epithelium after staining with rhodamine-phalloidin showed rearrangement of brush border actin filaments. Although tight junctions were intact, the apical region of the gut epithelium in rats with 40% TBSA burns was constricted, possibly because of contraction of brush border actin filaments. Changes in brush border structure and cytoskeletal organization were most pronounced in the ileum of rats 18 hours after injury. CONCLUSIONS: These findings suggest that disruption of the brush border cytoskeleton may, in part, be responsible for the loss of intestinal barrier function after thermal injury in animal models. PMID- 8367815 TI - Effect of a thromboxane synthetase inhibitor on protamine-induced circulatory changes in sheep. AB - BACKGROUND: Rapid intravenous administration of protamine after procedures requiring cardiopulmonary bypass is occasionally associated with severe pulmonary hypertension, systemic hypotension, cardiac dysfunction, and lung edema. We hypothesized that the mechanism for these hemodynamic changes after protamine administration is the release of thromboxane. We therefore examined the effect of a thromboxane synthetase inhibitor (OKY-046) on these hemodynamic changes in a sheep model. METHODS: Ten female sheep were prepared with lung lymph fistulas and balloon-tipped pulmonary artery, left atrial, arterial, and venous catheters. After a 5-day recovery period, 2 mg/kg protamine was infused 10 minutes after 200 units/kg heparin, with (n = 5; OKY-046 group) and without (n = 5; heparin/protamine group) OKY-046 (10 mg/kg). RESULTS: In the heparin/protamine group, pulmonary arterial pressure and lung lymphatic flow were significantly increased soon after administration of protamine, from 19 +/- 1 to 51 +/- 2 mm Hg and 5 +/- 1 to 8 +/- 1 ml/hr, respectively. The circulating leukocyte count was significantly reduced, from 3304 +/- 318 to 903 +/- 898 mm3. Cardiac output was also reduced, from 5.8 +/- 0.3 to 3.4 +/- 0.7 L/min/m2. These changes were completely blocked in the OKY-046 group, except for the neutrophil depletion and the increase in lung lymphatic flow. CONCLUSIONS: We conclude that thromboxane plays a significant role in protamine-induced hemodynamic deterioration and pulmonary permeability changes. PMID- 8367817 TI - Thrombosis of the descending thoracic aorta: a case report. AB - A 76-year-old woman with primary polycythemia vera had emboli to both superficial femoral arteries and to a branch of the superior mesenteric artery. Polycythemia vera is a neoplastic disease of bone marrow stem cells in which increased red cell production leads to hyperviscosity manifested by propensity to thromboembolic phenomena. These problems usually occur in smaller vessels, sparing large vessels that have high blood flow. The patient underwent an extensive investigation to determine the source of the emboli. Abdominal aortic angiograms and cardiac echogram failed to reveal the source. An esophageal echogram showed free-floating thrombus in the descending thoracic aorta, which was confirmed by magnetic resonance imaging. A thoracic aortic thrombectomy was performed. Embolic phenomena ceased and postoperative esophageal echogram confirmed a clear thoracic aorta. Although extremely rare in the descending thoracic aorta, thrombus formation may occur in association with polycythemia vera and should be sought when usual investigations fail to reveal the source. PMID- 8367818 TI - Popliteal venous aneurysms. AB - Popliteal venous aneurysms are rarely reported but represent a potentially life threatening condition requiring accurate diagnosis and surgical resection. Newer techniques including magnetic resonance imaging, computed tomography, and color flow duplex imaging offer new noninvasive methods to define popliteal fossa venous abnormalities. Excision of the aneurysm with venous reconstruction removes the embolic source and maintains prograde venous flow. A posterior surgical approach to the popliteal fossa is recommended to facilitate exposure. Early control of venous outflow is needed to avoid thromboembolism. This report describes the diagnosis and treatment of popliteal venous aneurysms in three patients with a review of the English-language literature. PMID- 8367819 TI - Liver infarct after sigmoid resection: an unusual case of mesenteric ischemia. AB - Hepatic infarction is an unusual event. A patient is described who had a hepatic infarct after a sigmoid resection. She was found to have occluded superior mesenteric and celiac arteries, with visceral circulation dependent on the inferior mesenteric artery. Disruption of the collateral circulation was presumed to have caused the subsequent liver infarct. A review of the pathophysiology of liver infarction is presented with particular reference to the relation of arterial occlusion to infarction. PMID- 8367820 TI - Laparoscopic splenectomy in the management of immune thrombocytopenia purpura. AB - The role of splenectomy in the management of immune thrombocytopenia purpura is well known. Recent improvements in laparoscopic technology have significantly expanded the variety of general surgical procedures amenable to a minimally invasive approach. An initial experience of four cases of immune thrombocytopenic purpura managed by laparoscopic splenectomy is presented. The entire procedure was completed under laparoscopic guidance in three of four cases, and a counterincision was required to control bleeding in one patient. The procedure is performed with five operating ports including a camera port, two retraction ports, and two dissection ports. Dissection begins at the lower pole of the spleen and progresses cephalad to the hilum where major vessels are individually ligated and divided. The short gastric vessels are divided with a linear laparoscopic stapler. The lateral peritoneal attachments are divided, and the spleen is removed intact through a 6 cm fascial incision at the umbilicus. Laparoscopic splenectomy appears to be a safe and efficacious procedure that is useful in the management of certain hematologic diseases and may ultimately be performed for a variety of pathologic conditions involving the spleen. PMID- 8367821 TI - Peripheral arterial thrombosis in the nephrotic syndrome. AB - Peripheral arterial thrombosis is a rare complication of nephrotic syndrome that occurs in conjunction with a hypercoagulable state and results in a high rate of limb loss and death. We report a case of brachial artery thrombosis in a pediatric patient with nephrotic syndrome, antithrombin III deficiency, and antecedent vessel trauma. An extensive review of the literature is presented. We conclude that management of arterial thrombosis requires aggressive replenishment of antithrombin III and adequate heparinization in addition to the traditional surgical management. Moreover, arterial puncture should be avoided because of the high risk of thrombosis in these patients. PMID- 8367822 TI - Intravascular ultrasonography for the diagnosis of traumatic aortic disruption: a case report. AB - Thoracic aortic disruptions after blunt trauma are highly lethal injuries. Diagnosis of these injuries has traditionally been based on clinical suspicion, chest radiographs, and aortography. The roles of dynamic computed tomography and transesophageal echocardiography are currently under investigation. Intravascular ultrasonography is a new technology with potential as a diagnostic adjunct in the evaluation of these injuries. We present a case of traumatic aortic disruption identified by intravascular ultrasonography after nondiagnostic aortography and dynamic computed tomography studies. PMID- 8367823 TI - Reflections on laparoscopic surgery. PMID- 8367824 TI - Studying experimental fetal cardiopathies. PMID- 8367825 TI - Interviewer bias and maternal bias. PMID- 8367826 TI - Clinical teratology counseling and consultation case report: low dose methotrexate exposure in the early weeks of pregnancy. PMID- 8367827 TI - Effects of 5-fluorouracil on embryonic rat palate in vitro: fusion in the absence of proliferation. AB - 5-Fluorouracil (5-FU) inhibits the enzyme thymidylate synthetase (TS) which results in inhibition of DNA synthesis. 5-FU is teratogenic in many species, inducing cleft palate, limb, and tail defects. In the present study, gestation day (GD) 14 embryonic rat craniofacial explants were exposed to 5-FU in organ culture with increasing concentrations and durations of exposure. Palates exposed to 5-FU were morphologically abnormal and craniofacial shape, size, and palatal fusion pattern were affected with the severity of effects dependent on concentration and duration of exposure. Cleft palate was induced in vitro as opposing palates overlapped in a narrowed oral cavity. Palates exposed to higher levels of 5-FU were growth inhibited, but fused even though proliferation ceased and few cells were available to participate in elevation and fusion. This was demonstrated as a biphasic concentration-response profile for palatal fusion in which 0.05 to 0.15 micrograms 5-FU/ml produced decreasing rates of palatal fusion, while exposure to 0.15 to 3.0 micrograms/ml resulted in progressively increasing rates of fusion. The effects of 5-FU were detected biochemically as a reduction in TS activity which was concentration and time dependent during the first 12 hours, with a return to control levels by 24 hours. During the first day, 5-FU did not alter protein levels, but DNA levels significantly decreased at the high concentration, 2.0 micrograms/ml. After 5 days in culture, both DNA and protein decreased with increasing 5-FU concentration and duration of exposure. Also by the end of the culture period, 3H-TdR incorporation had decreased in a concentration dependent manner. It is concluded that progressive inhibition of proliferation and growth in organ culture results in two different morphological outcomes: cleft palate resulting from a narrowed oral cavity and increased incidence of anterior palatal fusion under conditions of strong growth reduction. This study demonstrates that elevation and fusion can occur in the absence of growth and proliferation. Based on these observations, severe inhibition of growth or proliferation would not necessarily be sufficient to induce cleft palate. PMID- 8367828 TI - Effects of retinoic acid on cartilage differentiation in a chondrogenic cell line. AB - Previously we have isolated the monopotential chondrogenic cell line RCJ 3.1 C5.18 from the multipotential mesenchymal cell line RCJ 3.1 [Grigoriadis et al.: Endocrinology, 125:2103-2110, 1989]. When cultured for approximately 20 days under appropriate conditions, these cells from cartilage nodules. In the present investigation, we have used this cell line to study the effects of all-trans retinoic acid (RA) on chondroblast differentiation, cartilage formation, and cartilage degradation. Continuous exposure of cultures to RA (0.01-100 nM) inhibited chondroblast differentiation and glycosaminoglycan (GAG) accumulation in a dose-dependent manner, without comparable effects on cell growth. Pulse treatment with RA for various 4 day periods during a 17-24 day culture period established that RA inhibited differentiation of chondroprogenitors at all periods tested. These effects were reversible, except for part of the effect on early chondroprogenitors. Treatment with RA on days 13-17 in 17 day cultures not only resulted in cessation of cartilage formation, but also in disappearance of pre-existing cartilage nodules. We demonstrated that this was associated with RA induced downregulation of GAG synthesis and increased degradation of cartilage proteoglycans. Hence, the inhibitory effects of RA on cartilage formation consist of inhibition of chondroblast differentiation, inhibition of GAG synthesis by differentiated chondroblasts, and stimulation of cartilage proteoglycan degradation by differentiated chondroblasts and/or chondrocytes. These results indicate that the clonal monopotential chondrogenic cell line RCJ 3.1 C5.18 forms a good model system to study the effects of retinoids on cartilage differentiation, formation, and degradation. PMID- 8367829 TI - Risk factors for coarctation of the aorta. AB - To test the hypothesis that environmental factors during early pregnancy may cause coarctation of the aorta (CoA), 50 cases of CoA and 756 controls were studied. The cases represented all verified CoAs in Finland during 1982-1983 and controls were randomly selected from all babies born during the same period. Both case and control mothers were interviewed by midwives approximately 3 months after delivery. In these data 18 patients had pure CoA only and the remaining 32 at least one other cardiac anomaly. Three CoA patients had a chromosomal anomaly. The relatives of CoA babies had more congenital anomalies than those of the control babies. Maternal overall exposure to chemicals at work was slightly more prevalent among the CoA group (32.0%) than the control group (26.2%). Maternal exposure to mineral oil products at work during early pregnancy was more common among CoA cases (8.0%) than controls (1.4%) [odds ratio (OR) = 5.9, 95% confidence interval (CI95) = 1.8-19.2]. The risk of CoA was also associated with previous miscarriages (OR = 2.3, CI95 = 1.2-4.4) and twin birth (OR = 16.3, CI95 = 4.0-67) of the child. The risk of CoA was not associated with seasonal variation, maternal smoking, alcohol consumption, or use of deodorants. It is concluded that genetic factors explain only a small fraction of the causes of CoA and that many common environmental exposures during early pregnancy are unlikely to be real risk factors for CoA. However, the power of this study was weak for testing the teratogenicity of specific chemicals. PMID- 8367830 TI - Serotonin and cardiac morphogenesis in the mouse embryo. AB - The possible involvement of the neurotransmitter serotonin (5-HT) and its binding protein (SBP) in cardiac morphogenesis was studied using mouse whole embryo culture (together with immunocytochemistry or 3H-thymidine autoradiography) and a cell migration assay. Embryos were cultured before and during the period of endocardial cushion formation, embryonic (E) days 9-12, in the presence of 5-HT, the monoamine oxidase (MAO) inhibitor nialamide, or an uptake inhibitor (fluoxetine or sertraline). For the migration assay, cells from the outflow tracts of E12 embryos were dissociated and placed in a chemotaxis chamber together with different concentrations of 5-HT. E9 embryos cultured in the presence of 10 microM 5-HT and nialamide exhibited intense 5-HT immunoreactivity (5-HT IR) throughout the myocardium. This staining was greatly diminished by fluoxetine, sertraline, or the absence of nialamide. As morphogenesis proceeded, myocardial staining in embryos exposed to 5-HT became restricted to developing endocardial cushion forming regions and was more completely blocked by uptake inhibitors. No evidence for 5-HT synthesis by myocardium was found at any age studied using the precursor L-tryptophan. SBP was present in endocardial cushions in cultured and uncultured embryos. 3H-thymidine autoradiography demonstrated that both fluoxetine and sertraline inhibited proliferation of cardiac mesenchyme, endocardium, and myocardium. These effects were most pronounced when exposure began at E9 (prior to cushion formation). Dose-dependent effects of 5-HT on migration of outflow tract cells were also observed. Taken together, these results suggest that 5-HT may play a role in cardiac morphogenesis during endocardial cushion formation. PMID- 8367831 TI - Microsurgical study on the mechanisms determining sidedness of axial rotation in rat embryos. AB - Sidedness of left/right asymmetric body structures is strongly biased in most animals by mechanisms that are not well understood. In rat embryos, axial rotation starts at the 9-10 somite stage and is almost completed at the 17-18 somite stage. As a result, the ventrally flexed tail (caudal part of the body) and chorioallantoic placenta on the yolk sac take up their position normally on the right side of the embryo. Because the tail and chorion become connected via the allantois around the time when axial rotation takes place, we hypothesized that the allantois and possibly its connection to the chorion is important in determining sidedness of the tail. In the present study, we tested this hypothesis by surgically removing either the allantois or chorion before axial rotation started. Embryos were explanted at 8 AM on Day 9 of gestation (presomite stage), and either the allantois or chorion was removed using microforceps. Embryos were then cultured in rotating bottles, and sidedness of the tail, chorioallantoic placenta, and bulboventricular loop (heart) was determined after 50 hours (approximately 25-26 somite stage). Removal of the allantois (n = 55) resulted in absence of the umbilical cord and a 49.1% incidence of inverted tail; a chorioallantoic placenta-like structure developed on the yolk sac in the normal position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367832 TI - Expression of the IV (reversed and/or heterotaxic) phenotype in SWV mice. AB - Approximately 50% of iv/iv mice have situs inversus (mirror image reversal of viscera) and 40% have heterotaxia (anomalous arrangement of viscera). The occurrence of heterotaxia is independent of situs. Using the cross-intercross breeding system to put the iv gene on the SWV background, an occasional presumed iv/+ mouse was found that had an IV (situs inversus and/or heterotaxic) phenotype. Testcrosses of these reversed animals indicated an iv/+ genotype. Since iv is linked tightly to Igh-C on chromosome 12, we inferred the genotype with a polymorphism of Igh-C demonstrated using the polymerase chain reaction (PCR). This confirmed them to be iv/+. The expression of the IV phenotype in animals heterozygous for the iv gene may be due to an interaction of iv with an autosomal recessive gene found in SWV. We have not found the IV phenotype in heterozygous iv/+ mice following placement of the iv gene on six other inbred strains. Rarely, we also found that presumed SWV +/+ mice had the IV phenotype. Test matings of these phenodeviants, corroborated by PCR, have confirmed them to be +/+. Although the phenotypes of the affected SWV +/+ and iv/+ mice resembled those found in iv/iv mice, the occurrence of situs inversus and heterotaxia were not independent of each other, and most of the SWV mice with the IV phenotype had heterotaxia with situs solitus. This infrequent dominant expression of the iv gene has so far only been seen when iv is on the SWV background. These findings are consistent with the idea that this phenomenon is due to the interaction of the iv gene with another gene found so far only in the SWV strain. PMID- 8367833 TI - Penetrance and expressivity of acetazolamide-ectrodactyly provide a method to define a right-left teratogenic gradient that differs between the C57BL/6J and WB/ReJ mouse strains. AB - Penetrance or the frequency of embryos with any degree of forelimb ectrodactyly is the usual method to describe the forelimb ectrodactyly response of mouse embryos to acetazolamide. A digit score for number of small or absent digits for the separate right and left forelimb response to acetazolamide provides a measure of expressivity or the severity of response. We examine the relationship between expressivity and penetrance using right and left forelimb data from a previously reported dose-response analysis of the C57BL/6J and WB/ReJ strains to acetazolamide. The data show that expressivity and penetrance are highly correlated for the separate right and left forelimbs for both strains. In C57BL/6J, the dose-response analyses of both expressivity and penetrance of the separate right and left forelimbs demonstrate a teratogenic gradient, decreasing from right to left, that depends on the symmetrical ectrodactyly response of the right and left forelimbs. In WB/ReJ, the right forelimb is also more sensitive than the left, but the dose-response analyses of both penetrance and expressivity show the two forelimbs are asymmetrical in their ectrodactyly response and that there is not a simple teratogenic gradient in this strain. In WB/ReJ, the left forelimb is resistant at even the highest non-lethal doses. The high correlation between expressivity and penetrance for the separate forelimbs of both C57BL/6J and WB/ReJ suggests that this right-left difference between the two strains may not be a property of the limbs themselves but may be an intrinsic genetic difference between the two types of embryos perhaps in the amount of teratogen to which the embryos are exposed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367834 TI - Characterization of adhesion of "resting" and stimulated platelets to fibrinogen and its fragments. AB - Adhesion of resting and stimulated platelets to immobilized fibrinogen (Fg) was characterized using various forms of Fg, receptor peptide mimics, and antibodies to glycoprotein (GP) IIb/IIIa and Fg. Resting platelets adhered to Fg, but to less than half the extent of the same platelets stimulated with epinephrine/ADP. The adhesion of resting and stimulated platelets to Fg was inhibited by a receptor peptide mimic (G13, a peptide corresponding to residues 300-312 of GPIIb), anti-GPIIb/IIIa antibodies, and a monoclonal antibody (4A5) against the carboxyl terminus of the gamma chain of Fg. The results presented here demonstrate that the alpha chain RGD platelet recognition sites are not required to mediate the adhesion of either stimulated or resting platelets to immobilized Fg. Although stimulated platelets can adhere extensively to monomeric Fg containing one functional gamma chain, resting platelets require bivalent Fg containing two functional gamma chains to mediate irreversible adhesion to Fg. PMID- 8367835 TI - Recombinant plasminogen activator inhibitor-1 protects platelets against the inhibitory effects of plasmin. AB - Plasmin-induced degradation of platelet glycoprotein Ib (GPIb), the von Willebrand factor (vWF) receptor, has been implicated as a mechanism contributing to the development of platelet dysfunction following cardiopulmonary bypass (CPB). The goal of this study was to assess whether biologically active recombinant plasminogen activator inhibitor-1 (rPAI-1), could antagonize the inhibitory effects of plasmin on GPIb. GPIb function, as evaluated by measuring vWF-dependent, ristocetin-induced platelet agglutination in human platelet rich plasma (PRP) was significantly impaired following incubation with plasmin (60 +/- 14% inhibition, p < 0.01). Inclusion of rPAI-1 (10 micrograms/ml) in the PRP antagonized this plasmin effect, restoring agglutination to 92 +/- 8% of the control value (p < 0.01). The effect of rPAI-1 on the enzymatic activity of plasmin was further evaluated in an amidolytic assay with the plasmin substrate S2251 where an apparent second order rate constant of plasmin inhibition by rPAI 1 of 9.4 x 10(4) M-1 S-1 was determined. Our results suggest that rPAI-1, by inhibiting both tissue plasminogen activator-induced plasmin generation and plasmin activity directly, may have clinical value for improving platelet function during and after CPB. PMID- 8367836 TI - Superiority of plasma 11-dehydro-TXB2 to TXB2 as an index of in vivo TX formation in rabbits after dosing of CS-518, a TX synthase inhibitor. AB - We compared plasma 11-dhTXB2 and TXB2 for their ability to reflect in vivo TX formation in rabbits treated with AA and CS-518, a TX synthase inhibitor. The average plasma level of TXB2 in rabbits was much higher than that of 11-dhTXB2, probably because of artificial formation of TXB2 during blood sampling. CS-518 (1 mg/kg, p.o.) caused a long-lasting suppression of the 11-dhTXB2 level, and its inhibitory effect on 11-dhTXB2 was much more extensive than that on TXB2. AA infusion for 5 min resulted in transient and remarkable increases of both TXs, and prevention of such increases by CS-518 pretreatment (1 mg/kg, i.v.) was shown: inhibitions of 11-dhTXB2 and TXB2 were 85% and 40%, respectively. The inhibitory effect caused by CS-518, which was more clearly observed on plasma 11 dhTXB2 than on TXB2, was due to not only the completely inhibited levels without artificial formation but also the durable high levels based on the long half-life of 11-dhTXB2 in AA-infused rabbits. CS-518 injection during sustained AA-infusion also resulted in a 2-fold faster disappearance of plasma 11-dhTXB2 than was seen without CS-518, despite its long half-life. Considering the absence of artificial formation, the long half-life, and the good response to change of TX formation, plasma 11-dhTXB2 is superior to TXB2 as an index for monitoring in vivo TX synthase activity and its pharmacological modification with AA and CS-518. PMID- 8367837 TI - M(r) 6,400 aurin tricarboxylic acid directly activates platelets. AB - ATA is a novel anticoagulant polymeric anionic aromatic compound that inhibits von Willebrand factor binding to platelet glycoprotein Ib and thereby prevents ristocetin- and shear stress-induced platelet aggregation. To investigate its mechanism of action, ATA fractions of homogeneous M(r) have been prepared by size exclusion chromatography. ATA fractions of M(r) > or = 2,500 are most effective at inhibiting vWF-mediated platelet aggregation, and ATA of M(r) = 2,500 also inhibits thrombin-induced platelet activation. Paradoxical results were observed in studies of ATA with M(r) = 6,400. This fraction of ATA stimulates aggregation of washed platelets or platelet-rich-plasma. The dose/response of aggregation shows a bell-shaped curve with maximal aggregation at approximately 2 micrograms/ml. Platelet aggregation is associated with phosphoinositide turnover and protein kinase C- and calcium-dependent protein phosphorylation. Platelet signalling responses to ATA are inhibited by platelet pretreatment with PGI2 or dibutyryl-cyclic AMP, but are unaffected by inhibiting platelet cyclooxygenase with aspirin. These results suggest that M(r) 6,400 ATA directly activates platelet phospholipase C to initiate platelet aggregation. This effect, unique to M(r) 6,400 ATA, could potentially mitigate ATA's beneficial anti-thrombotic effect on vWF-mediated platelet responses, and should be considered when analyzing results of experiments that utilize unfractionated ATA. PMID- 8367838 TI - Effect of different sample preparation methods on the results of the impedance technique in the study of platelet hyper- and hypo-function in whole blood. PMID- 8367839 TI - Supplementation-induced changes in polyunsaturated fatty acid membrane and plasma composition do not modify mononuclear cell procoagulant activity. PMID- 8367840 TI - [Pasteurella anatipestifer: a controllable farm problem]. AB - The performance of 13 flocks of ducks on a duck farm decreased markedly. Post mortem and bacteriological examinations indicated that Pasteurella anatipestifer was a major cause, although Salmonella spp., Escherichia coli and Treponema spp. were also detected. Use of an autovaccine against Pasteurella anatipestifer markedly reduced the signs and symptoms in the second part of fattening period. PMID- 8367841 TI - [Salmonellosis in the horse]. AB - Salmonellosis is a worldwide problem of both men and animals. Equine salmonellosis is an increasing problem and a review of the recent knowledge is given. Etiology, symptomatology, diagnostic procedures, therapy and prevention are discussed. PMID- 8367842 TI - [A study of uterine adhesions following suturing of the uterus with catgut or Vicryl in cesarean sections in cattle]. AB - A caesarean section was performed in 202 cows for the first time. The uterus of 103 of these cows was sutured with Vicryl (7 metric) and the uterus of 99 cows was sutured with plain catgut (9 metric). The cows were randomly allotted to the two groups. All cows were rectally examined to diagnose adhesions between the uterus and the surrounding tissue five weeks post partum. Adhesions were found in 50% of the cases. There were no differences in the number of adhesions and the severity of the adhesions between the catgut and the Vicryl group (Table 1). PMID- 8367843 TI - [Practice management with computers is increasingly more businesslike. Interview by Sophie Deleu]. PMID- 8367844 TI - [Effect of nutrition on growth and skeletal development in dogs]. PMID- 8367845 TI - [Selenium values too low]. PMID- 8367846 TI - [Embryonal mortality in swine: conditions for a low incidence]. AB - Embryonic mortality is an important cause of reproductive losses in the pig. The embryonic mortality rate, 30 per cent on average, will be reduced under optimal management conditions if (1) all sows are inseminated between 10 and 25 hours before ovulation; (2) semen of boars of proven fertility is used; and (3) variation in embryonic development is small. The uterine capacity of sows should also improved to enable the lower mortality rate to be expressed in larger litters. PMID- 8367847 TI - [A severe Aspergillus flavus infection in slaughtering chicks and the effect of disinfection with enilconazole: a case study]. AB - In a flock of chicks, the number of birds dying per day from infection with especially Aspergillus flavus increased up to 1% during the second half of the fattening period. Levels of Aspergillus flavus were measured before and after cleaning of the chicken house with the anti-mycotic agent eniconazole (Clinafarm, Janssen Pharmaceutical Company, BV). The cleaning and disinfection schedule followed reduced levels if Aspergillus flavus to zero. PMID- 8367848 TI - [Arbitration]. PMID- 8367850 TI - [Feed for parrots]. PMID- 8367849 TI - [Study of analgesics at the time of purchase inspection]. PMID- 8367851 TI - Surgery for tricuspid insufficiency: long-term follow-up after De Vega annuloplasty. AB - Between 1975 and 1991, 97 consecutive patients underwent De Vega tricuspid annuloplasty either isolated or in combination with mitral, aortic, or mitral and aortic valve procedures. Preoperatively 96.9% of the patients were in New York Heart Association functional class III or IV. Causes of tricuspid insufficiency were functional tricuspid ring dilatation and a combination of dilatation and different organic tricuspid valve lesions. There were 17 early deaths (17.5%), primarily due to cardiac failure, none was related to the tricuspid annuloplasty. 80 perioperative survivors have been followed up for a mean of 4.7 +/- 4.1 years with a total of 462 cumulative patient-years. Actuarial 5-, 10-, and 15-year survival rates, including early deaths, were 64% +/- 5%, 48 +/- 6%, and 26% +/- 10%. Recurrence of tricuspid regurgitation was rated as moderate in 15% and severe in 18.8%. Ten patients required reoperation (2.2%/patient-year), of whom 8 were associated with tricuspid regurgitation (1.7%/patient-year). Although in all patients but one the De Vega annuloplasty was intact, the tricuspid ring was dilated; 4 patients had additional tricuspid organic valve lesions. 6 of the 8 patients had concomitant mitral valve or mitral prosthesis dysfunction. 26 patients died late (5.6%/patient-year) due to chronic cardiac failure in 50% and after reoperation in 7% of the patients. 4 patients had implantation of a permanent pacemaker (0.9%/patient-year). 54 patients (67.5%) are still alive, with 43% having no and 17.5% having only mild residual tricuspid regurgitation. De Vega annuloplasty is indicated with tricuspid insufficiency due to functional ring dilatation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367852 TI - Permanent epicardial and transvenous single- and dual-chamber cardiac pacing in children. AB - Between January 1974 and November 1991 33 children received a permanent single- or dual-chamber pacing system, mainly because of postoperative high-degree AV block. The children were followed up retrospectively for pacemaker- and lead related complications, and for differences between epi- and endocardial stimulation. The overall rate of lead related complications was 35% and did not differ significantly between the epi- and endocardially paced groups, although it tended to be somewhat higher in the epicardially paced children, mainly due to a higher rate of exit blocks in the latter. The epicardially stimulated patients exhibited a significantly higher rate of pacemaker-related complications, which was primarily accounted for by a higher frequency of battery depletions in the epicardial systems. The most impressive differences between both groups, however, was seen with respect to subacute and chronic energy consumption. Chronic energy drain in the epicardially paced patients amounted to almost the sixfold of that seen in the endocardially stimulated children. This resulted in a significantly shorter cumulative pacemaker survival in the epicardial group. Therefore, it is concluded that, whenever possible, the transvenous approach be used in children and small infants too. However, as a rule, in the latter transvenous dualchamber pacing is usually not feasible. In these cases rate-adaptive single-chamber pacing has evolved as a reasonable alternative for improving hemodynamics as well as quality of life. In epicardial pacing the use of pulse generators allowing bidirectional telemetry is advisable. In this way monitoring of lead impedance and battery status can be performed noninvasively, thus permitting individualization of pulse widths and amplitude setting, which is important with respect to energy conservation. PMID- 8367853 TI - Total cavopulmonary anastomosis: selection criteria related to postoperative results. AB - In this study we review our experience with total cavopulmonary anastomosis (modified Fontan procedure) which was performed in 31 patients. One patient died from postoperative cardiac low-output syndrome, the other died from a neurological complication (early mortality 6.5%). During a mean follow-up period of 15 months there was no late mortality. Preoperative assessment showed that one, two, or three of the Choussat criteria (defining the ideal Fontan candidate) were not fulfilled by 39%, 16% and 6% of our patients. In the 2 patients who died 2 and 3 of those criteria were not fulfilled. Poor outcome could not be predicted based on assessment of the pulmonary artery size (expressed as the McGoon-ratio or the Nakata-index) alone. In order to assess the relationship of pulmonary artery size and pulmonary arteriolar resistance (PVR) as a predictor of outcome, we introduced two new indices (McGoon-ratio/PVR and Nakata-index/PVR). The patient who died from poor postoperative hemodynamics had the lowest values of all patients. Among the 29 survivors we did not observe significant acquired postoperative arrhythmias. In our experience the total cavopulmonary anastomosis can be performed with a low mortality and good postoperative results. Patients who do not fulfill at least 8 of the Choussat criteria and children with a low ratio of pulmonary artery size to PVR are high-risk patients. In these children we recommend either a bidirectional Glenn anastomosis as a first-step procedure or a total cavopulmonary anastomosis with a fenestration of the intraatrial tunnel. PMID- 8367854 TI - Low-dose anticoagulant management of patients with St. Jude Medical mechanical valve prostheses. AB - Between February 1984 and December 1990, 622 St. Jude Medical valves were implanted in 548 patients. There were 382 males (69.7%) and 166 females (30.3%) with a mean age of 32.3 +/- 11.9 years (range 9-68 years). Sixty-eight percent of the patients were referred from rural areas. Three hundred and forty patients underwent aortic valve replacement (AVR), 134 had mitral valve replacement (MVR), and 74 had aortic and mitral valve replacement (DVR). The hospital mortality was 4.7% (16/340) for AVR, 6.7% (9/134) for MVR and 10.8% (8/74) for DVR. Follow-up period ranged from 1.1 to 7.2 years. Total follow-up was 1317.3 patient-years (py). All patients received 2.5 mg warfarin, 225 mg dipyridamole, and 250 mg aspirin daily, regardless of prothrombin time and cardiac rhythm. Thromboembolism was observed in 10 patients (0.75 py); there were 3 mortalities (0.22% py). Valve thrombosis occurred in 4 patients (0.30% py): 3 in the MVR group (0.94% py) and 1 in the AVR group (0.11% py). Hemorrhage occurred in 19 patients (1.44% py) with 11 fatal outcomes (0.83% py). It is concluded that a random daily dose of 2.5 mg warfarin with 225 mg dipyridamole and 250 mg aspirin is sufficient for safe anticoagulation without the need for serial prothrombin-time adjustments. PMID- 8367855 TI - The influence of age and other risk factors on the results of coronary reoperation. AB - In a retrospective analysis of 115 patients who underwent a coronary reoperation between 1984 and 1989, we studied the influence of age and other risk factors on the perioperative morbidity and mortality and on the long-term results. The mean age of the population was 59.4 years, 55 patients were below 60, 52 between 60 and 70 and 8 patients over 70 years, respectively. The distribution of risk factors was similar to other populations suffering from coronary heart disease. The mean time between first and second coronary operation was 7.1 years. Complete revascularisation at the reoperation could be achieved in only 20.9% (n = 24) of the patients. A mean of 1.9 vein grafts were implanted. The perioperative mortality (within 30 days) was 5.2% (n = 6) for the whole group, whereas the highest mortality rate could be observed in the patients aged over 70 with 25% (n = 2). The incidence of perioperative complications was also higher in the elderly patients, comparing them to the whole group. Mean follow-up time was 39 months. During follow up 14 patients (12.4%) died, most of the deaths were cardiac related. The cumulative survival rate was 91% after one, 90% after three, and 88% after five years. We found no statistically significant differences in the survival rates and the myocardial infarction rates regarding the different age groups. The exercise capacity and functional status at the time of follow up were quite acceptable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367856 TI - Multiple system organ failure after open heart surgery in infants and children. AB - Between January 1985 and March 1989 we retrospectively observed multiple system organ failure (MSOF) in 16 of 460 children (3.5%) who underwent cardiac surgery with cardiopulmonary bypass for congenital heart disease. MSOF was arbitrarily defined as a clinical entity with failure of two or more vital organ systems associated with high fever, thrombocytopenia, and cardiocirculatory insufficiency and occurring within the first postoperative week. In 13 children the first clinical manifestations of MSOF were evident on the first post-operative day and in the other 3 on the second or third post-operative day. All children showed acute renal failure, acute hepatic failure, high fever, and thrombocytopenia. Most of them showed respiratory insufficiency and neurological involvement. Seven of the 16 children died. Four of the 9 surviving patients had neurological sequelae still present 6 months after the operation, and the others recovered completely. PMID- 8367857 TI - Reproducibility of assessment of left-ventricular function using intraoperative transesophageal echocardiography. AB - Reproducibility of results is an important point in assessing the utility of intraoperative transesophageal echocardiography for evaluating changes in left ventricular function. The purpose of the present study was to define the intra- and interobserver reproducibility of the qualitative assessment of left ventricular regional wall motion and the quantitative assessment of global left ventricular function. In addition, the interstudy reproducibility of two examinations was tested when the probe was displaced and replaced in the esophagus. A transesophageal short-axis view at the level of the papillary muscles was obtained in 86 patients undergoing cardiac surgery. In the 80 patients with adequate images, regional wall motion was visually graded and area ejection fraction was calculated by two observers and assessment was repeated by the same observer one day later. The same observer graded wall motion differently in only 5% (24/480) of segments. Grading by two observers differed in 9% (43/480) of segments. Assessment differed by one grade at the most and in not more than 2 out of 6 segments per patient. Repeated measurements of area ejection fraction (AEF) by the same observer correlated well (r = 0.97 before and r = 0.97 after cardiopulmonary bypass) with a mean percent difference of 6%. A similarly close correlation was found for measurements of two observers (r = 0.90 and r = 0.93, respectively) with a mean percent difference of 10% for area ejection fraction. The correlation for the first and second examination in the same patient by one observer was acceptable (r = 0.78 and r = 0.80, respectively) with a mean percent difference of 15% for area ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367859 TI - Surgical treatment of pulmonary and pleuro-pulmonary Aspergillus disease. AB - Between 6/87 and 3/92 22 out of 24 patients were treated (22 by surgery) for pulmonary and pleural Aspergillus disease. The most frequent lung disorder was tuberculosis (9 x), followed by bronchiectasis (5 x), congenital lung cysts (2 x), pneumonia with abscess formation (2 x), sarcoidosis (2 x), and bronchial cancer (4 x). More than half the patients had further severe secondary diseases. 4 patients with "simple aspergilloma" and 5 patients with "complex aspergilloma" underwent lobectomy or segmentectomy without complications or recurrence. Special surgical problems occurred in 13 patients with inflammation involving pleura and chest wall (pleuro-pulmonary aspergillosis, pleural aspergillosis) and invasive lung changes (invasive pulmonary aspergillosis). 7 patients developed an empyema after lung resection, on 4 occasions with bronchopleural fistula. In 4 cases myoplasty, in 2 cases thoracomyoplasty, on 2 occasions completion pneumonectomy with omentoplasty, in one case omentoplasty alone, and on 2 occasions decortication with pleurectomy and lung resection lead to a complete cure. 2 open window thoracostomies were constructed. In 15 cases a single operation was adequate. In 7 patients up to 3 further operations were necessary. 17 patients had haemoptysis, in 10 of these cases it was recurrent. On 7 occasions life threatening haemorrhage took place, causing death in 2 cases. These were the only deaths resulting from the lung disease. Our results show that aggressive surgical action can be successful. Myoplasty, thoracomyoplasty, and omentoplasty are, in our view, the most suitable measures for healing pleura empyemas and bronchopleural fistulae coincident with pleuro-pulmonary aspergillosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8367858 TI - Effects of trehalose in preservation of canine lung for transplants. AB - The effect of trehalose, a non-reducing disaccharide which stabilizes and protects membranes, in the preservation of canine lungs was examined when Euro Collins solution was basically used as a preservant. In group I, five lungs were perfused and preserved in an Euro-Collins solution modified by replacing the glucose with 35.0 g/L of trehalose. Five control lungs (group II) were perfused and preserved with Euro-Collins solution containing 35.0 g/L glucose. In both groups, no vasodilators were used. After preservation for 12 hours, left lung allotransplantation was performed. At 10, 40, 70, and 130 minutes after reperfusion, the right pulmonary artery was clamped for 10 minutes and four parameters were measured: arterial oxygen tension, mean pulmonary arterial pressure, peak inspiratory pressure, and wet/dry weight ratios. The transplanted lung was also examined histologically. At 10, 40, 70, and 130 minutes after reperfusion, oxygen-tension levels from group I were 263.2 +/- 19.2, 283.4 +/- 14.0, 277.5 +/- 19.9 and 264.9 +/- 26.2 mmHg, respectively. In group II, the corresponding values were 191.2 +/- 33.9, 188.0 +/- 40.3, 153.4 +/- 40.0 and 134.7 +/- 49.4 mmHg, respectively. At 70 and 130 minutes the difference were significant (p < 0.05). All transplanted lungs from group I showed normal histology, whereas four dogs in group II developed severe pulmonary edema and one had a partially edematous lung. These findings suggest that simple substitution of trehalose for glucose has a beneficial effect on preservation of canine lung for 12 hours. PMID- 8367860 TI - Retrieval of broken left-atrial catheter using a rigid bronchoscope. AB - Left-atrial pressure monitoring continues to be of value in cardiac surgery of the high-risk patient. Complications are fortunately low and include haemorrhage following catheter removal and retained catheter fragments. A simple and safe technique is presented to retrieve retained catheters using a rigid bronchoscope and avoiding the need for resternotomy. PMID- 8367861 TI - Fractured strut of Bjork-Shiley 70 degrees convexo-concave mitral valve prosthesis found in left coronary artery. Use of a portable transcutaneous cardiopulmonary bypass system for successful valve replacement. AB - Strut fractures followed by disk escape of Bjork-Shiley convexo-concave valve prostheses are a well-known problem. This article discusses the case of a successfully treated patient who was admitted to our institution with extreme and prolonged cardiogenic shock. The strut was dislodged into the main stem of the left coronary artery and the disk into the iuxtarenal abdominal aorta. The intent of this report is, in particular, to illustrate the management problems. Immediately after diagnosis, circulation and oxygenation were ensured by use of a portable cardiopulmonary bypass support (CPS) system whose circulation lines were introduced subcutaneously. Thus the transfer to the operating room and the surgical intervention were able to start under controlled conditions. The disk was removed by Fogarty catheter manoevre without any problems during the same operation, using a transpericardial access to the descending thoracic aorta. In our opinion, the primary insertion of the CPS and the avoidance of an additional laparotomy in disk removal help promote the survival of such critically ill patients. PMID- 8367862 TI - Aortobronchial fistula: a late complication of coarctation repair by patch aortoplasty. AB - A case of aortobronchial fistula occurring 13 years after coarctation repair by patch aortoplasty is presented. Correct diagnosis was established by computed tomographic scanning and magnetic resonance imaging. Surgical treatment consisted of simple closure of the bronchial defect and interposition of a Dacron graft under partial extracorporeal bypass. PMID- 8367863 TI - Minimally invasive surgery in the thorax. PMID- 8367864 TI - Statement of the Commission for Minimally Invasive Surgery of the German Society of Thoracic Surgery. PMID- 8367865 TI - Prerequisites, indications, and techniques of video-assisted thoracoscopic surgery. AB - During the last two years video-assisted operative thoracoscopy has introduced new impetus into thoracic surgery. Today it is viewed as a sparing and safe alternative to thoracotomy for a wide spectrum of indications. The prerequisites, instruments, and operative techniques are discussed. In oncological thoracic surgery it still remains to be verified whether the criteria of radicality are fulfilled by this new technique. Using video-assisted operative thoracoscopy, we have successfully operated on 209 patients with the following indications: recurrent pneumothorax (n = 94), interstitial lung disease (n = 25), coin lesion (n = 20), pleural effusion (n = 17), hyperhidrosis (n = 14), mediastinal tumor or lymphoma (n = 10), thoracic empyema (n = 9), bullous emphysema (n = 8), pleural tumor (n = 5), hematothorax (n = 3), malignant pericardial effusion (n = 3), and chylothorax (n = 1). The advantages of this minimally traumatizing operating technique lie in a better view of the operative site, the objectively measurable reduction in postoperative restriction, less pain, earlier postoperative mobilization, and shorter hospital stay. This operating technique, in addition to being sparing, requires markedly less time than a thoracotomy. The disadvantages are the two-dimensional monitor picture and, especially, the loss of palpation. PMID- 8367866 TI - Clinical experience with minimally invasive thoracic surgery. AB - From October 1991 to June 1992 video-endoscopic lung surgery was applied in a total of 109 patients. In the first case a pulmonary cyst measuring 15 x 18 cm was resected. In 21 patients lung nodules were exstirpated by means of wedge resection. Moreover, metastasectomies, open lung biopsies, parietal pleurectomies, resections of bullae, and decortications, as well as 3 lower-lobe lobectomies were performed using video-endoscopic procedures. Closure of lung parenchyma was carried out using the 3 cm Endo-GIA stapler (Autosuture). In none of the patients were we forced to enlarge the intervention to a thoracotomy because of technical problems. Indications, operative technique and results are presented. This new technique offers all the known advantages of minimally invasive surgery to patients requiring thoracic surgery. PMID- 8367867 TI - Long-term myocardial function after heart transplantation. AB - With an increasing number of heart transplantations and an improved survival rate a characterization of the long-term hemodynamic profile of the transplanted heart is necessary. 222 cardiac catheterizations were performed in 71 heart recipients under cyclosporine A immunosuppression during a 7-year follow-up after transplantation. Hemodynamic evaluation revealed a non-progressive arterial hypertension due to an increased systemic vascular resistance, leading to a mild increase of left-ventricular chamber stiffness. Parameters of systolic myocardial function were found to be normal and did not deteriorate during the 7 year period. The prevalence of allograft coronary angiopathy increased from 13% one year to 54% five years after transplantation. Myocardial function was neither adversely influenced by the presence of coronary angiopathy nor by the number or severity of former rejection episodes. Unchanged annual pressure-volume loops excluded the development of a dilated or restrictive posttransplantation cardiomyopathy. Thus, not the myocardial function, but the coronary angiopathy represents the most critical cardiac long-term problem after transplantation. PMID- 8367868 TI - Third-time coronary artery revascularization. AB - Eighteen patients underwent a third coronary artery revascularization (rere-CABG) between 1983 and 1991. The factors necessitating rere-CABG were graft failure in 83% of the patients and progression of native coronary atherosclerosis in 17%. Mean interval between the second and third operation was 49.1 months. Median sternotomy and cardiopulmonary bypass (CPB) were used in 12 patients, a left thoracotomy approach was used in 6 (with CPB in 3 patients and without CPB in 3). The mean revascularization rate was 2.2 (grafts/patient). The internal thoracic artery was employed in 12 patients and the right gastroepiploic artery was used in one. Operative mortality was 11.1% (2 deaths). Non-fatal perioperative myocardial infarction, reexploration for bleeding, and respiratory failure occurred in one patient each. There were no other serious complications. Long term follow-up was obtained in 15 of the 16 survivors. Four patients had recurrence of angina pectoris, and one late death due to myocardial infarction occurred. The myocardial event-free rate was 75% at 3.4 years. This experience indicates that a third coronary revascularization can be justified: operative approach and choice of graft material have to be individualized, but adequate long-term results can be obtained. PMID- 8367869 TI - A reconsideration of surgery for mitral stenosis based on the extent of valvular distortion shown by two-dimensional echocardiography preoperatively. AB - A twelve-year follow-up study was carried out with 98 consecutive patients operated on for pure mitral stenosis with open mitral commissurotomy (OMC) or valve replacement with porcine valves (MVR). Each patient had the extent of valve distortion diagnosed preoperatively by two-dimensional echocardiography as either grade I of the dome-formation type, grade II of the intermediate type, or grade III of the mass-formation type. Thirty grade I patients and 24 grade II patients underwent OMC and 44 grade III patients received MVR. The long-term survival and reoperation rates were significantly poorer with grade II than grade I patients and there was no statistical significance between grades II and III. However, the clinical conditions set by NYHA are significantly worse in grade II than in grade III. This can be clearly explained by the fact that the left atrial volume decreasing ratio (LAVDR) in the latest period, which was measured in patients with more than 7 years survival, remained nearly at the early postoperative value in grade III, while the LAVDR of grade II at the latest period grew worse and became insignificantly different from the preoperative values. This study clearly shows that when OMC is applied to grade II patients, frequent reoperations might be necessary because of poor hemodynamic conditions. Thus, it might be better to adopt MVR rather than OMC with grade II patients with moderately distorted mitral valves. PMID- 8367870 TI - Combined perioperative infusion of nifedipine and metoprolol provides antiischemic and antiarrhythmic protection in patients undergoing elective aortocoronary bypass surgery. AB - A randomized study was performed on 70 patients undergoing elective coronary bypass surgery to examine whether the combined, perioperative, 24-hour infusion of the calcium-channel blocker nifedipine (10 micrograms/kg/h) and the beta 1 blocker metoprolol (12 micrograms/kg/h) reduces the incidence of perioperative myocardial ischemia and arrhythmias (group NM, n = 34). The control group received nifedipine only (n = 36). Repeated assessment of serum enzyme levels (CK, CK-MB) and 12-lead ECG, together with 3-channel Holter monitoring over 48 h were used to define perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and supraventricular and ventricular arrhythmias. The two groups did not significantly differ with respect to preoperative anamnestic and surgical data. No perioperative myocardial infarction was detected in either group. However, a significantly lower incidence of transient ischemic events was observed in the NM group as compared to the nifedipine group (3% versus 11%; p < 0.05). In addition, there was a tendency towards lower CK-MB levels and peak values of CK- and CK-MB in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia (9%) and atrial flutter/fibrillation (6%) in the NM group as compared to the nifedipine group (33 and 27%, p < 0.05). In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening of the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single drug regimen with nifedipine. PMID- 8367871 TI - A technique for internal mammary artery to coronary artery anastomoses. AB - A "no-touch" technique for anastomosing the internal mammary artery to the anterior descending artery is described. This technique has been used in more than 3000 patients, and enables one to construct a long, patulous anastomosis in which all suturing is forehand. PMID- 8367872 TI - Three-dimensional vascular imaging--an additional diagnostic tool. AB - Angiography is still the standard for imaging of vascular structures. However, since the number of projections is limited, complex pathoanatomy may not be sufficiently visible. This study presents two patients in whom 3D reconstruction from Spiral CT data revealed combined vascular lesions undisclosed by angiography. In one case the combination of coarctation and chronic dissection type B, in another the combination of two aneurysms of the celiac trunk in series was disclosed. We conclude that 3D reconstruction can be a valuable asset in the diagnosis of complex vascular pathoanatomy. PMID- 8367873 TI - Effects of pulsatile and nonpulsatile perfusion mode during extracorporeal circulation--a comparative clinical study. PMID- 8367874 TI - Multiple pulmonary-artery aneurysms due to mucoid vasculopathy--angiographic and histological observations. AB - Multiple peripheral pulmonary artery aneurysms were diagnosed by computed tomography and confirmed angiographically in a 7-year-old boy. On histological examination unusual mucoid vasculopathic changes were noted in the pulmonary artery aneurysms and pulmonary vasculature as a part of systemic vascular involvement. This case demonstrates a new association between mucoid vasculopathic changes and pulmonary aneurysms. Mucoid vasculopathy could represent one more disorder having a causative role in the etiology of intrapulmonary arterial aneurysms. PMID- 8367875 TI - Combined transection of the trachea and esophagus following cervical blunt trauma. AB - The successful management of a patient with combined transection of the cervical trachea and esophagus following blunt trauma is reported. This type of injury was rare in the past, but is gradually increasing at the present time because of the increased use of motorcycles. Immediate primary closure of the transected trachea and esophagus offers the best chance for a good result. PMID- 8367876 TI - Closure of acute bronchial stump insufficiency with a musculus latissimus dorsi flap. AB - We describe a successful closure of an acute bronchial stump insufficiency after pneumonectomy by intrathoracic transposition of the pedunculated latissimus dorsi muscle: A 56-year-old patient with a necrotizing bronchial carcinoma developed a stump insufficiency after right pneumonectomy. Repeated resection and renewed closure of the completely dehiscent stump was not possible, as the stem bronchus had been separated close to the tracheal bifurcation in the preceding operation. Therefore we transposed the pedunculated musculus latissimus dorsi into the thoracic cavity. The closure of the bronchial stump insufficiency was achieved by fixation of the muscle on to the open stump and surrounding tissue of the mediastinal pleura with fibrin glue. The postoperative course was without complications, no further insufficiency or empyema developed. PMID- 8367877 TI - Complete prosthetic valve thrombosis despite several thrombolytic treatments after tricuspid valve replacement. AB - We discuss the case of a 50-year-old man who underwent tricuspid valve replacement with a mechanical prosthesis (Duromedics) due to traumatic tricuspid insufficiency following a blunt chest trauma fifteen years previously. Despite correct anticoagulation therapy several events of prosthetic valve thrombosis occurred in the following years. The patient was treated four times by thrombolytic therapy. Finally, seven years after the initial operation the mechanical valve was replaced by a Carpentier-Edwards bioprosthesis because of complete blockage. PMID- 8367878 TI - Cardiac surgery in Germany during 1992. A report by the German Society for Thoracic and Cardiovascular Surgery. PMID- 8367879 TI - Exposure to 2,3,7,8-tetrachlorodibenzo-para-dioxin leads to defective dentin formation and pulpal perforation in rat incisor tooth. AB - A single dose of 1000 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg body weight was given to TCDD-resistant (Han/Wistar) young adult male rats. Changes in the skulls and the continuously erupting incisor teeth were evaluated 16 weeks after the administration of TCDD. The skulls of the experimental rats (N = 11) were significantly smaller than those of the control rats (N = 11), and the upper and lower incisor teeth of all experimental rats were significantly thinner than the control rat teeth. The pulps of the lower incisors of all experimental rats were lingually exposed to the oral cavity at their incisal ends. Also in 3 cases the pulps of the upper incisors were exposed, but never in the control rats. Whereas the labial surfaces of the incisors of the control rats were brown, those of the experimental rat teeth appeared greyish and mottled. Histological examination revealed that the pulp chambers in the incisal halves of the affected teeth were larger than normal, at the expense of the thickness of dentin. Towards the incisal tooth ends, odontoblasts gradually lost their polarity and the pulp tissue became necrotic. A dentin zone next to the pulp chambers was irregular. Lingual tapering of the teeth was pronounced, which gave them a mesiodistally flattened appearance. The superficial zone of the otherwise regular enamel was poorly pigmented. In conclusion, a single injection of TCDD was shown to impair normal growth of the skull and incisor tooth formation in rats. The small size of the incisors, their aberrant shape and the defective dentin (and enamel) formation could be mediated by vitamin A metabolism, known to be interfered with by TCDD. PMID- 8367880 TI - Developmental patterns of aluminum in mouse brain and effects of dietary aluminum excess on manganese deficiency. AB - Previous studies have shown that excess dietary Al during development can affect neurobehavioral measures and decrease tissue Mn of 21-day-old weanling mice without a corresponding increase in tissue Al concentrations. Al and Mn have similar tissue concentrations and similar affinities for transferrin, which is the major plasma transport protein for Al and Mn as well as Fe. In the present study, brain Al, Mn and Fe were studied at 6, 12, 18 and 24 days of age in offspring of Swiss Webster mice fed a semipurified diet containing excess Al (Al[+], 1000 micrograms Al/g diet, Al as Al lactate), marginal Mn (Mn[-], 3 micrograms Mn/g diet) or both excess Al and marginal Mn (Al[+]Mn[-]) from conception to day 24 postnatal (weaning on day 18). Brain Al concentrations were higher at 6 days of age than at later ages and were significantly elevated by the excess Al diet (P = 0.017) but returned to control levels by weaning. Brain Mn concentrations increased from day 6 to day 24 and were lower in the Mn deficient groups (P < 0.001) and also in the excess Al group (P = 0.024) than in controls. Brain Fe concentrations were not influenced by diet. Similar patterns were seen in liver as in brain. The marginal Mn diet led to postnatal growth retardation which was more severe in litters of dams fed Al[+]Mn[-] diets than in litters fed Mn[-] diet. These data suggest that excess Al in diet can interact specifically with Mn metabolism during development. PMID- 8367881 TI - Effect of different renal glutathione levels on renal mercury disposition and excretion in the rat. AB - Mercury renal disposition has been studied following HgCl2 injection (5.0 mg/kg body wt., s.c.) in controls, diethylmaleate and N-acetylcysteine-treated rats. The different treatments were used to generate statistically different degrees of non-protein sulfhydryls concentration in kidneys. Diethylmaleate (4 mmol/kg body wt., i.p.) diminished kidney glutathione levels to 25% and N-acetylcysteine (2 mmol/kg body wt., i.p.) increased kidney non-protein sulfhydryls levels up to 75% compared with new controls. The amount of mercury in the kidneys, the mercury excretion rate in urine and the mercury plasma disappearance curves were calculated during 3 h post HgCl2 injection. BUN was measured in plasma at the same time period to determine the onset of kidney damage. The results indicate a higher HgCl2 renal clearance in N-acetylcysteine-treated rats compared to controls and less renal mercury accumulation. The data agree with diminished renal toxicity. On the other hand, renal mercury accumulation was higher and mercury renal clearance lower in diethylmaleate-treated animals, associated with higher renal toxicity. The results suggest that non-protein sulfhydryl levels (principally glutathione) might determine renal accumulation of mercury as well as its elimination rate and hence might enhance or mitigate the nephrotoxicity induced by the metal. PMID- 8367882 TI - Effects on neurobehavioral performance of chronic exposure to chemically contaminated well water. AB - Occupational exposure to trichloroethylene (TCE) and other solvents impairs neurobehavioral performance. Use of well water contaminated with TCE and solvents has been associated with excessive symptoms, cancers, birth defects and impaired blink reflex. We extended these observations by measuring the neurophysiological (NPH) and neuropsychological (NPS) status of subjects who used water contaminated with 6 to 500 ppb of TCE for 1 to 25 years. The 170 well-water exposed subjects who resided in southwest Tucson, Arizona overlying the Santa Cruz River aquifer, were compared to 68 referent subjects for NPH and NPS tests. Also, 113 histology technicians (HT) were referents for blink reflex latency only. Affective status was assayed by a Profile of Mood States (POMS). Exposed subjects were statistically significantly impaired when compared to referents for NPH tests. These impairments included sway speed with eyes open and closed, blink reflex latency (R-1), eye closure speed, and two choice visual reaction time. NPS status was statistically significant impaired for Culture Fair (intelligence) scores, recall of stories, visual recall, digit span, block design, recognition of fingertip numbers, grooved pegboard and Trail making A and B. POMS scores were elevated. Prolonged residential exposure to well-water containing TCE at lower levels than occupational exposures, but without time away from exposure for metabolism and excretion of toxins, was associated with neurobehavioral impairment. PMID- 8367883 TI - Primary aromatic amines from side-stream cigarette smoke are common contaminants of indoor air. AB - A very sensitive mass-spectrometry method has been developed for the analysis of aromatic amines in tobacco smoke and in indoor air. Cigarettes were smoked with a smoking machine; the amines from the smoke were trapped in a 5% HCl water solution containing internal standards and detected by gas chromatography/mass spectrometry in the selected-ion-monitoring (SIM) mode. The amines measured were the following: aniline, 2-toluidine, 3-toluidine, 4-toluidine, 2-ethylaniline, 3 ethylaniline, 4-ethylaniline, 2,3-dimethylaniline, 2,4-dimethylaniline, 2,5 dimethylaniline, 2,6-dimethylaniline, 1-naphthylamine, 2-naphthylamine, 2-methyl 1-naphthylamine, 2-aminobiphenyl, 3-aminobiphenyl and 4-aminobiphenyl. We analyzed nine brands of cigarettes sold commercially in Italy (Gauloise, Nazionali, Marlboro, Camel, MS, MS mild and MS lights), with and without filter. Main-stream smoke contained a lower amount of aromatic amines than side-stream smoke: the total level of these amines in main-stream smoke ranged from 200 to 1300 ng/cigarette, whereas the level of aromatic amines in side-stream smoke varied from 20,000 to 30,000 ng/cigarette. The smoke of black-tobacco cigarettes had higher levels of aromatic amines compared to light-tobacco cigarettes and the filters significantly reduced aromatic amines in main-stream smoke. We also determined the levels of aromatic amines in ambient air, offices and houses. Some aromatic amines (aniline and toluidine) were detected in ambient air, as well as in rooms of non-smokers. Most measurements showed a considerable contamination of aromatic amines derived from side-stream smoke, which was detected also in parts of the buildings in which smoking was not allowed. PMID- 8367884 TI - Liver carcinogenesis is not a predicted outcome of chemically induced hepatocyte proliferation. AB - Cell proliferation has long been recognized as a basic component of multistage carcinogenesis. Based largely on the finding that certain nongenotoxic chemical carcinogens induce cell proliferation in the same organ that develops tumors after long-term exposure, some suggest that the increased rates of cell division account for the carcinogenicity of these chemicals. This paper examines relationships between chemically induced liver toxicity, cell proliferation, and liver carcinogenesis; major factors include consistency, transient vs. sustained dose-response correspondence, and scientific plausibility. For a presumed mechanism to be valid, a sustained proliferative response is critical, largely because transient increases in hepatocyte proliferation are not sufficient to induce cancer or promote liver tumor development. A consistent association between liver toxicity and carcinogenicity has not been established. Our evaluation of studies on purported relationships between chemically induced cell proliferation and liver carcinogenesis shows: 1) that inconsistencies in sex and species specificity exist, 2) that a large percentage of proliferative responses are transient, 3) that inconsistencies in response to various hepatic peroxisome proliferators are common, and 4) that dose-response and duration relationships have not been sufficiently examined. Studies of proliferative responses of putative preneoplastic cells in the liver indicate that these cells divide faster than normal hepatocytes and also have higher death rates. Chemicals that induce cell proliferation in preneoplastic foci do not always provide a persistent increase in replication rates, even with continuous exposure. A selective growth advantage to preneoplastic cells in the liver may be provided either by an enhancement of the replication rates of these cells compared to the surrounding normal hepatocytes, by inhibition of cell loss, or by inhibition of the growth rate of normal cells. More work is needed to understand how chemical carcinogens and noncarcinogens affect cell division and cell loss of normal hepatocytes and of preneoplastic cells; measurements of hepatocyte proliferation alone are not sufficient to elucidate mechanisms of liver tumor development or to predict liver carcinogenesis. Because of our limited knowledge of the complex molecular changes occurring during liver cancer, it would be inappropriate and far too premature to amend scientific risk assessment procedures for nongenotoxic chemical carcinogens based on oversimplified or incompletely tested speculations. PMID- 8367885 TI - Chlorine gas exposure and the lung: a review. AB - We conducted a review of the literature detailing the respiratory effects of chlorine, an extremely important but toxic halogen. Historically, the heaviest mass inhalational exposures to chlorine resulted from World War I gassing. Currently potential human exposure to chlorine inhalation occurs in a variety of settings in the workplace, as a result of inadvertent environmental releases, and even in the home due to household cleaning mishaps. Chlorine species are highly reactive; tissue injury results from exposure to chlorine, hydrochloric acid, hypochlorous acid, or chloramines. Acute, high level exposure to chlorine gas in occupational or environmental settings results in a variety of dose-related lung effects ranging from respiratory mucus membrane irritation to pulmonary edema. Pulmonary function testing can reveal either obstructive or restrictive deficits immediately following exposure, with resolution over time in the majority of cases. However, some of those exposed may demonstrate long-term persistent obstructive or restrictive pulmonary deficits or increased nonspecific airway reactivity after high level exposure to chlorine gas. Symptoms and signs following inhalation of mixtures of chlorine-containing cleaners in the home are similar to those after occupational exposures and environmental releases. Although generally less severe, these events may be extremely common. Controlled human exposure data suggest that some subjects may be more responsive to the effects of chlorine gas; epidemiologic data also indicate that certain subpopulations (e.g., smokers) may be at greater risk of adverse outcome after chlorine inhalation. Although these findings are intriguing, additional study is needed to better delineate the risk factors that predispose toward the development of long-term pulmonary sequelae following chlorine gas exposure. PMID- 8367886 TI - N-methyl-N'-nitroguanidine: irritation, sensitization, and acute oral toxicity, genotoxicity, and methods for analysis in biological samples. AB - Currently, N-methyl-N'-nitroguanidine (MNG) is being considered by the U.S. Air Force Armament Laboratory for use in explosive formulations. A mammalian toxicity profile has been performed which includes the analysis of chemical impurities and an assessment of the potential for the metabolism of MNG to 1-methyl-3-nitro-1 nitrosoguanidine (MNNG). Potential in situ gastric conversion of MNG to MNNG is a toxicological concern because MNNG is both mutagenic and carcinogenic. The compound was also evaluated in several bioassays to assess its potential genotoxic activity. The acute oral toxicity was determined in male and female Fischer 344 rats administered a single dose of MNG in corn oil. The maximum suspension of MNG that could be delivered, 1 mg MNG/kg body weight, produced no signs of toxic stress during the 14-day observation period. The primary eye and skin irritation potential of MNG was determined in female New Zealand white rabbits using the Draize technique. MNG produced no irritation to intact skin but did produce mild conjunctival irritation. The response of a single guinea pig to the dermal sensitization evaluation indicated that MNG is a weak sensitizer. The results of three genetic tests indicated that MNG does not interact with genetic material. Gastric contents and feces from treated animals showed no evidence of conversion of MNG to MNNG. PMID- 8367887 TI - Liver function in rats treated individually and with a combination of xylene, toluene and methanol. AB - The individual and combined influences of three industrial solvents (namely xylene, toluene, and methanol) on certain parameters of liver function in laboratory rats have been studied. Although individual treatments with all three solvents elevated activities of serum enzymes (i.e., GOT, GTP, and alkaline phosphatase), and did manifest hyperbilirubinemia, nevertheless metabolic interaction occurring after their combined treatment suggested a weak antagonistic mechanism. This assumption has been supported by the fact that the detoxification ability of the liver, as indicated by the formation of hippuric acid, improved after the combined treatment. PMID- 8367888 TI - Occupational skin hazards from synthetic plastics. AB - Epoxy and acrylic resins have numerous industrial applications but are also widely used in the household environment. These compounds are presently one of the most important sources of occupational contact dermatitis. Contact sensitization to epoxy resins is usually caused by the resin itself but hardeners or other additives, such as reactive diluents, plasticizers, fillers and pigments, can occasionally be responsible. Since completely cured epoxy resins are not sensitizers, epoxy resin sensitization is always due to the presence, in the final polymer, of uncured allergenic low molecular weight oligomers. Acrylates are now considered the fourth most common cause of contact sensitization due to resins. Unpolymerized monomers of acrylic compounds are known to be responsible for the contact allergy. Accelerators, inhibitors and catalysts, which are usually added to the acrylates to promote the polymerization process, can also sensitize. Both allergic and irritant contact dermatitis may be caused by exposure to epoxy or acrylic resins and their additives. Contact urticaria, allergic or irritant airborne contact dermatitis caused by volatile compounds, onychia and paronychia can also occur. From January of 1984 to May of 1992 we detected 39 cases of occupational allergic contact dermatitis to epoxy resin system substances and 11 cases of occupational contact sensitization to acrylic compounds. In our experience, the electronics industry as well as paint and glue related activities were the most important sources of epoxy sensitization. Dental materials and anaerobic sealants were found to be the most frequent acrylate sensitizers. PMID- 8367889 TI - Characterization of highly polar DNA adducts derived from dibenz[A,H]anthracene (DBA), 3,4-dihydroxy-3,4-dihydro-DBA, and 3,4,10,11-tetrahydroxy-3,4,10,11 tetrahydro-DBA. AB - Two highly polar DNA adducts were found after metabolic activation of 3,4,10,11 tetrahydroxy-3,4,10,11-tetrahydrodibenz[a,h]anthracene (DBA-3,4,10,11-bisdiol) by liver microsomes isolated from male Sprague-Dawley rats pretreated with Aroclor 1254 in presence of calf thymus DNA. These DNA adducts could be assigned to the metabolites of dibenz[a,h]anthracene (DBA), of 3R,4R,10R,11R-tetrahydroxy 3,4,10,11-tetrahydro-DBA and of 3R,4R,10S,11S-tetrahydroxy-3,4,10,11-tetrahydro DBA. DNA adducts derived from metabolites of 3S,4S,10S,11S-tetrahydroxy-3,4,10,11 tetrahydro-DBA were not found. These highly polar adducts also could be detected by reversed phase HPLC after incubation of dibenz[a,h]anthracene, 3R,4R-dihydroxy 3,4-dihydro-DBA ((-)-DBA-3,4-diol) and 3S,4S-dihydroxy-3,4-dihydro-DBA ((+)-DBA 3,4-diol) with DNA in presence of the activating system. After incubation of 14C labelled DBA DNA adducts derived from DBA-3,4,10,11-bisdiol were found in a fraction of 38% and bay region 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydro-DBA-DNA adducts at a level of 25%. DBA-3,4,10,11-bisdiol exhibited a higher DNA binding yield (38 +/- 12 pmol/mg DNA) than (-)-DBA-3,4-diol (23 +/- 6 pmol/mg DNA), the most mutagenic 3,4-diol enantiomer. For (+)-DBA-3,4-diol the highly polar DNA adducts derived from DBA-3,4,10,11-bisdiol were by far the most predominant adducts in vitro. PMID- 8367891 TI - Oxisterol determination in selected coffees. AB - The main aim of green-coffee processing techniques, such as decaffeination and roasting, is always to maintain a very high level of quality in taste and flavor, the beverage's most important characteristics to consumers. Oxidative alterations of coffee lipids, which can occur in roasting, exert a very marked influence on these quality traits. Determining the extent of oxidation thus can provide an indication of the product's potential shelf-life and reveal traces of any newly formed oxidative products that might prove nutritionally unsafe. Yet, while much attention has recently been focused on certain by-products induced by cholesterol oxidation and their proven toxicity as risk factors in atherosclerosis and cancer, oxidated phytosterols have largely gone unnoticed, being considered along with beta-sitosterol as not very dangerous in that neither is absorbed by the intestinal tract. The present study investigates the substances derived from phytosterol oxidation (oxisterols) in samples of regular and decaffeinated commercial coffees. The findings show that oxisterols were absent in some samples and that the traces of oxidate phytosterols detected in others were well below the threshold considered as toxicologically active. PMID- 8367890 TI - Lys- and Leu-aminopeptidase activity after acute toluene exposure in the rat brain. AB - Changes in Lys- and Leu-aminopeptidase activities in several brain regions of the rat, after acute toluene administration, are described in this research. Aminopeptidase activity has been suggested as a candidate regulator of the degradation of several neuroactive peptides. Lys-aminopeptidase activity was significantly decreased in the thalamus, amygdala, and medulla oblongata. Leu aminopeptidase activity was significantly decreased in the thalamus and cerebellum. It is suggested that these aminopeptidase activities could play a part in the mechanism of toluene neurotoxicity. PMID- 8367892 TI - Possible role of free radical intermediates in hepatotoxicity of hydrazine derivatives. AB - Hydrazine derivatives constitute a wide group of compounds and have found application in industry, agriculture, and (as therapeutical agents) medicine. In spite of their widely spread use, several hydrazine derivatives are known to exert hepatotoxic effects and are carcinogenic. Free radical species are produced during the hepatic biotransformation of alkylhydrazines by both rat and humans liver microsomes. Cytochrome P-450 dependent monoxygenase system is responsible for the production of these reactive species and specific cytochrome P-450 isoenzymes appear to catalyze the formation of free radical intermediates. Free radicals generated during the metabolism of alkylhydrazines are capable of inducing oxidative stress in isolated hepatocytes and might contribute to the development of cell injury. PMID- 8367893 TI - Purification and characterization of hepatic P-450IIE1 from acetone-treated mice. AB - A new cytochrome P-450 isozyme (Mr = 52,000) was purified to apparent electrophoretic homogeneity from hepatic microsomes of mice treated with acetone and its biochemical, spectral, and immunological properties characterized. Several criteria indicated that the purified cytochrome was distinct from the known mouse P-450 isozymes. The absolute spectrum of its oxidized form indicated that it was in the high spin state. In a reconstituted system, it showed low catalytic activities towards 7-ethoxycoumarin, aminopyrine, and coumarin, whereas it catalyzed the oxidation of aniline, acetone, dimethylnitrosamine with high turnover number. The mouse enzyme was immunoreactive with polyclonal antibodies against rat P-450IIE1 and exhibited an NH2-terminal aminoacid sequence with a high homology to that of rat-P-450IIE1. Based upon the above catalytic, spectral, immunological and structural properties, the purified mouse P-450 appears to be the ortholog of previously described P-450IIE1(s) of other species. PMID- 8367894 TI - On the origin of the "six non-natural things" in Galen. PMID- 8367895 TI - Galen and Egypt. PMID- 8367896 TI - Apollonius and Galen on "joints". PMID- 8367897 TI - Galen on Hellenistics and Hippocrateans: contemporary battles and past authorities. PMID- 8367898 TI - [Galen as mental healer]. PMID- 8367899 TI - [Hellenistic science in the newly discovered Galen comment on Hippocratic writings "On the environment"]. PMID- 8367900 TI - [Comments on editing revisions of Galen's manuscript "On autopsy of cadavers"]. PMID- 8367902 TI - [Galen and medieval Armenian medicine]. PMID- 8367901 TI - [Theoretical, empirical and semantic aspects of water in Galen]. PMID- 8367903 TI - Galen and the utility of logic. PMID- 8367904 TI - Galen and Stoicism. PMID- 8367905 TI - [The nerves of the soul]. PMID- 8367906 TI - [Stoicism and stoics in Galen's manuscript De foetuum formatione]. PMID- 8367907 TI - [Galen on the topic of creation]. PMID- 8367908 TI - Water distributions of hydrated biological specimens by valence electron energy loss spectroscopy. AB - A technique has been developed for measuring the water distribution in thin frozen hydrated biological specimens by means of electron energy loss spectroscopy (EELS). The method depends on the quantification of subtle changes in the valence electron excitation spectrum as a function of composition. It involves determining the single-scattering intensities, calculating oscillator strengths and applying a multiple-least-squares fitting procedure to reference spectra for water and the organic constituents. The direct EELS approach has an important advantage over other indirect methods that are based on X-ray generation or elastic scattering measurements since these are applied to freeze dried specimens where differential shrinkage between compartments may produce errors. Precision and accuracy of the EELS method have been tested on cryosectioned solution of bovine serum albumin; data have also been obtained from cryosections of rapidly frozen erythrocytes. Results suggest that a precision of better than +/- 5% (s.d.) is attainable from a single measurement and the accuracy may be as high as +/- 2% if repeated measurements are made. The lateral spatial resolution of the water determinations is limited by radiation damage to approximately 100 nm which is of the same order as the specimen thickness. PMID- 8367909 TI - Effect of probe force on the resolution of atomic force microscopy of DNA. AB - Experimental results are presented to show that the adhesion force is the single most important limiting factor in high-resolution atomic force microscopy of DNA in air, prepared by the cytochrome-C-assisted spreading method. It is also shown that humidity plays a minor role in the control of probe force. Using a pure carbon film as the substrate to clean the AFM tip prior to imaging, it is demonstrated that 4-6 nm resolution on DNA can be routinely obtained by the atomic force microscope with commercial Si3N4 pyramid cantilevers. We also show that in organic solvents a resolution of up to 3 nm can be obtained under optimal conditions. PMID- 8367910 TI - [A low dosage pile, until menopause, will facilitate medical practice.. Interview by Robert Henry]. PMID- 8367911 TI - [Back pain: a disabling disease, costly and demoralizing. Interview by Robert Henry]. PMID- 8367912 TI - [A patient presenting with severe thrombocytopenia]. PMID- 8367913 TI - [Acquired hyperostosis syndrome]. PMID- 8367914 TI - [The limits of medicine and a life without limits]. PMID- 8367915 TI - [Periodic medical examination. Update 1992. 2. Systematic screening using prenatal ultrasonography. The Canadian Study Group for Periodic Medical Examination]. PMID- 8367916 TI - [Is extracorporeal membrane oxygenation necessary?]. AB - In order to evaluate our hospital center needs for extracorporeal membrane oxygenation (ECMO), a retrospective study was carried out over a two-year-period to determine the mortality rates of infants < or = 35 weeks of gestation and > or = 2000 grams with severe respiratory failure. The data was obtained from a perinatal center that serves a population that has 50,000 newborn deliveries per year. During the period of the study there were 75 infants meeting the above criteria admitted to the NICU with severe respiratory failure (defined as need for mechanical ventilation and 100% O2). Forty-four patients were excluded because of improvement of their respiratory status on conventional therapy, and 16 were ineligible for ECMO because of their primary diagnosis. Of the 15 infants considered ECMO candidates, there were 2 deaths as a result of streptococcal beta hemolytic septicemia. The result of this study showed that few infants in the population served by this perinatal center would have benefited from ECMO. PMID- 8367918 TI - [The possible relation between hepatitis B vaccination and chronic fatigue syndrome]. PMID- 8367917 TI - [Hypothalamic astrocytoma presenting as obesity with hypogonadism]. AB - We report herein a case of a 30 year old male patient who consulted for a long standing obesity since childhood. Clinical examination reveals the presence of hypogonadism and gynecomastia without galactorrhea. Endocrine assessment showed an hypogonadotrophic hypogonadism with a moderate insufficiency of the adrenocortical axis. Neuro-ophthalmological examination disclosed an inferior bitemporal quadranopsia. MRI showed an extra-axial suprasellar mass, lightly hypointense in T1 and hyperintense in T2. After craniotomy and conservative biopsy, pathological examination of the tumor showed regular cells surrounded with collagen and reticulin marked with immunoperoxidase against S100 protein and GFAP (glial fibrinolytic acidic protein) strongly suggesting the diagnosis of juvenile pilocytic astrocytoma. PMID- 8367919 TI - Questioning the value of screening for prostate cancer in asymptomatic men. PMID- 8367920 TI - Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center. AB - Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer. PMID- 8367921 TI - Anatomy of cavernous nerves distal to prostate: microdissection study in adult male cadavers. AB - Retrograde and antegrade dissections from the penile hilum to the prostatic area and the glans penis were performed in 4 formalin-preserved adult male cadavers. In addition to the medial branches accompanying the urethra, the lateral branches of the cavernous nerves pierced the urogenital diaphragm 4 to 7 mm from the striated muscles of the external sphincter. At the penile region, multiple communications between the cavernous and dorsal nerves were noted that suggest that either the cavernous nerves use the dorsal nerve as a carrier to the distal portion of the penis or the dorsal nerve may itself contain autonomic fibers. These findings will improve our ability to preserve erectile function during pelvic, urethral, and penile surgery. PMID- 8367922 TI - Silicone gel-filled testicular prosthesis and systemic disease. AB - Concerns exist regarding a possible link between the presence of silicone implants and the development of systemic disease. A retrospective review was carried out to determine whether or not a pattern of diseases could be found after the implantation of a testicular prosthesis. A specific pattern of diseases did not emerge in a group of 34 men harboring a scrotal silicone gel implant for a mean period of over five years. The findings, with a limited population and period of follow-up, are not conclusive but provide basis for reassurance to men about the health implications of their implants. PMID- 8367924 TI - Laparoscopic seromyotomy (auto-augmentation) for non-neurogenic neurogenic bladder in a child: initial case report. AB - An eight-year-old boy with lifelong urinary incontinence secondary to non neurogenic neurogenic bladder underwent successful laparoscopic seromyotomy (auto augmentation) with resultant cure of his incontinence. The ability to perform this laparoscopically with its seventy-minute operating time, decreased hospital stay, and improved cosmesis militates for its consideration before a standard augmentation is performed. PMID- 8367923 TI - Effect of obesity and fertility status on sex steroid levels in men. AB - Endocrine studies were performed on fertile and infertile obese men and compared with fertile and infertile nonobese men in order to determine the independent and codependent effects of obesity and fertility status on the male hypothalamic pituitary gonadal axis. The obese infertile group exhibited significant endocrinologic changes as compared with fertile nonobese control group which was not observed in any of the other three groups. Serum testosterone was significantly lower. The testosterone/estradiol ratio was significantly lower despite a lack of significant change in serum estradiol levels. Serum steroid hormone binding globulin (SHBG) was significantly lower which correlated with elevated bioavailability of both testosterone and estradiol in the obese infertile group. Serum luteinizing hormone levels were no different, suggesting that free testosterone levels were unchanged. Obese infertile men exhibit endocrinologic changes that are not observed in men with either obesity or infertility alone. Reduction of serum SHBG, total testosterone, and testosterone/estradiol ratio appear to be a marker of infertility among obese men. PMID- 8367925 TI - Pituitary gonadal dysfunction in adolescents with varicocele. AB - Gonadotropin-releasing hormone stimulation testing was performed on 104 adolescent males with a unilateral left varicocele to determine the frequency of testicular dysfunction in this group of patients. An abnormal test result was noted in approximately 30 percent of varicocele patients. We believe that an abnormal test result indicates a higher risk for future fertility problems, and early treatment may reduce this risk. PMID- 8367926 TI - Formation of ileal conduit utilizing ileal patch from augmentation cystoplasty. PMID- 8367927 TI - Long-term follow-up of ventriculoureteral shunts for treatment of hydrocephalus. AB - Surgical relief of hydrocephalus is achieved mainly with ventriculoperitoneal or ventriculoatrial shunting. In some patients, frequent reoperations are required because of infection, obstruction, or other complications, thus subjecting them to excessive operative morbidity and risk of neurological damage. One option that has been rarely addressed in recent years is drainage of cerebral spinal fluid into the urinary tract by way of a ventriculoureteral shunt. Patients who have endured multiple revisions of standard cerebral spinal fluid shunts may benefit from a relatively lower frequency of reoperation following ventriculoureteral shunting. There are several complications peculiar to this procedure, however, including ascending infection from the bladder, proximal shunt migration out of the ureter or distal migration into the bladder, failed urinary diversion, and electrolyte disturbances associated with volume depletion. Long-term follow-up of patients with ventriculoureteral shunts has not been reported. We describe the course of 4 patients successfully treated with ventriculoureteral shunts for an average of more than five years per patient. Although all eventually required reoperation, the frequency of reoperation with the ventriculoureteral shunts was markedly lower than with the standard shunts in these patients. Ventriculoureteral shunting should be considered for cerebral spinal fluid drainage in selected patients with multiple failures of standard shunts, provided the bladder is a low pressure reservoir with no urine infection. PMID- 8367928 TI - Obturator neuropathy after laparoscopic pelvic lymphadenectomy. AB - A case of obturator nerve injury with delayed manifestation following laparoscopic pelvic lymphadenectomy is presented. While the incidence of obturator nerve injury does not appear to differ between open surgical and laparoscopic approaches, the laparoscopic approach demands unequivocal visualization of the nerve when utilizing electrocautery because of the risk of nerve injury from thermal conduction through apposed tissues. PMID- 8367929 TI - Laparoscopic gonadectomy in a case of testicular feminization. AB - Laparoscopy provides a minimally invasive technique for the accurate diagnosis of intersex problems and may also provide the opportunity for therapeutic management of these patients. Herein, we report our management of a patient with complete testicular feminization, by laparoscopic bilateral gonadectomy of fully developed intra-abdominal testes. PMID- 8367930 TI - Hemangioma of penis and scrotum. AB - Hemangiomas of the genitalia are extremely rare. A hemangioma is self-limited and usually resolves spontaneously, therefore conservative treatment is generally recommended. However, genital hemangiomas may require surgical treatment if they become symptomatic. Herein we report a case of hemangioma of the penis and scrotum requiring surgical excision. The natural history and alternative treatments of hemangiomas are described. PMID- 8367931 TI - Labial fusion causing upper urinary tract obstruction. AB - An infant with dense and nearly complete labial fusion had marked hydroureteronephrosis which resolved after incision of the adherent labia. Although this is an unusual consequence of labial fusion, it argues for upper urinary tract screening in these children. PMID- 8367932 TI - Ultrasound characteristics of renal cryosurgery. AB - The ability to visualize renal cryosurgery using ultrasound was tested in an animal model. Five dogs underwent open laparotomy and ultrasound-monitored cryosurgery of both kidneys. On each kidney two cryolesions were made. The borders of the frozen region were identified on ultrasound as a hyperechoic rim created by the interface between frozen and unfrozen tissue. The thawed cryolesion appeared hyperechoic compared with the unfrozen kidney. Excellent correlation between the ultrasound and autopsy measurements of the cryolesions was obtained. Knowing this, renal cryosurgery under ultrasound monitoring may be possible. PMID- 8367933 TI - Automated evaluation of urethral obstruction. AB - The measurement of detrusor pressure and flow rate during voiding is the only way to objectively measure or grade infravesical obstruction. The resulting data cannot be interpreted easily. Manual as well as automatic methods have been introduced to derive one or several factors or parameters to quantify urethral resistance. A number of these methods are described in this overview. Since automatic methods involving computers guarantee uniform, unbiased, and objective processing of data, besides enabling the use of (statistical) methods that take into account more than one or two of the measured pressure and flow rate values, emphasis is on these methods. Some clinical results obtained with such automatic methods are discussed to illustrate the clinical value and possible impact on diagnosis and evaluation of treatment of lower urinary tract disorders. PMID- 8367934 TI - Detrusor instability in primary enuresis. PMID- 8367935 TI - Various protein and albumin corrections of the serum fructosamine concentration in the diagnosis of canine diabetes mellitus. AB - Fructosamines are formed when glucose reacts non-enzymatically with amino groups on proteins, and previous studies have indicated that the serum fructosamine concentration could be of importance in the diagnosis of canine diabetes mellitus. Owing to the connection between the protein/albumin concentration and serum fructosamine concentration, it has been suggested that the serum fructosamine concentration should be corrected for the protein/albumin concentration. Thus, the purpose of the present study was to evaluate the uncorrected serum fructosamine concentration and various protein and albumin corrections of the serum fructosamine concentration in the separation of dogs with diabetes mellitus from dogs with other diseases that presented with clinical signs suggestive of diabetes mellitus. The evaluation was assisted by relative operating characteristic curves (ROC curves), which may be used to compare various diagnostic tests under equivalent conditions (equal true positive ratios or false positive ratios) and over the entire range of cutoff values. A total of 58 dogs (15 dogs with diabetes mellitus and 43 dogs with other diseases) were included in the study. Serum fructosamine concentration, serum total protein concentration and serum albumin concentration were measured in each dog, and various corrections of the serum fructosamine concentration for protein or albumin concentration were made. Comparing the ROC curves of the uncorrected and each corrected serum fructosamine concentration indicated that there was no decisive difference between the uncorrected and the corrected serum fructosamine concentrations in discriminating between dogs with and without diabetes mellitus. Hence, correcting the serum fructosamine concentration as a routine procedure cannot be advocated from the results of the study. Moreover, the sensitivity and specificity of the uncorrected serum fructosamine concentration were very high, 0.93 and 0.95, respectively, further evidence of the value of the uncorrected serum fructosamine concentration in the diagnosis of canine diabetes mellitus. PMID- 8367936 TI - Systemic responses to challenge infection with Haemonchus contortus in immune Merino sheep. AB - Some systemic responses to single-dose infection with 10,000 Haemonchus contortus infective larvae were examined in sheep already shown to have protective immunity against the parasite. The major haematological finding was a neutrophil leukocytosis that occurred after the infections became patent but not during the pre-patent period. There was no definitive eosinophilia and no discernible change in the erythrocyte parameters. Systemic hyperthermia was not conclusively evident during the pre-patent period. Enzyme-linked-immunosorbent assays (ELISA) were used to measure the secondary anti-helminth antibody response in serum during the pre-patent period when the establishment of patent infection is resisted. These ELISAs employed preparations from adult worms to represent the parasitic stages of the worm, preparations from infective larvae to represent the pre-parasitic stages of the worm, and exsheathing fluid, which is the soluble material obtained when H. contortus larvae undergo ecdysis and transform from the pre-parasitic to the parasitic phase. Antibody responses to the three preparations differed qualitatively, indicating the presence of three different but perhaps overlapping sets of antigens. The three peaks in antibody against exsheathing fluid may reflect the pulses of antigen delivered to sheep as the parasite undergoes its three moults within the host. PMID- 8367937 TI - A standardized oral zinc tolerance test for assessment of zinc absorption in dogs. AB - Three oral zinc tolerance tests using increasing doses of elemental zinc (0.5, 0.75 and 1.0 mg/kg) given as zinc sulphate (ZnSO4.7H2O) were carried out in eight normal beagles. The zinc tolerance curves obtained were similar to those described in man, with the peak plasma zinc concentration occurring 2 h after dosing. There was a considerable variation between individual animals in the peak plasma zinc concentration achieved with each dose. This would appear to limit the value of a zinc tolerance test in assessing the efficiency of zinc absorption in individuals, although it may be of value in making comparisons between groups of dogs. PMID- 8367938 TI - The effect of storage at low temperature on the haemolytic complement activity of chicken serum. PMID- 8367939 TI - Transient stray voltage: is it detrimental to growth performance, health status and welfare of market pigs? AB - The effects of transient stray voltage associated with an alternating current were evaluated in growing-finishing pigs from 9 to 22 weeks of age. Seventy-two pigs were assigned to 9 blocks of 8 animals each. In each block, the following treatments were randomly distributed: a constant voltage differential created between the feeder or drinker and the metallic floor (woven wire), at a level of 0 volt plus 2-volt pulses (0 V-2 V), 2 volts plus 3-volt pulses (2 V-5 V), 5 volts plus 3-volt pulses (5 V-8 V), and a control treatment without any voltage differential (0 V-0 V). The constant voltage was applied 24 h per day. The pulses of 3 s duration were in the form of an increase in the amplitude of the constant 60-Hz signal. One pulse appeared every 20, 40 and 100 s during the hour following feed distribution and every 60, 120 and 300 s during the rest of the day. The animals were fed ad libitum and received fresh feed twice per day. Once during the 2-week periods at 9-10, 13-14, 17-18 and 21-22 weeks of age, the behaviour of the pigs was recorded during the hour following the two daily feed distributions. Animal weights and blood samples were taken every 2 weeks, from 9 to 21 weeks of age. No significant effect of transient stray voltage on any of the variables measured for the feeding, drinking, sitting or lying activities was found (p > 0.05). At 9-10 weeks of age, the number of rooting bouts was higher for the 5 V-8 V treatment (p = 0.03) and the number of events of butting the penmate was higher for the 2 V-5 V treatment (p = 0.05). Although the water and feed intake did not differ between treatments (p > or = 0.39), the average daily gain of the control group was lower than that of treated groups (p = 0.04) at 9 and 10 weeks of age, while the pigs submitted to a 2 V-5 V treatment had a higher daily gain than the pigs in the other treatment groups (p = 0.05) at 17 and 18 weeks of age.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8367940 TI - Molecular cloning and sequencing of coat protein-encoding cDNA of rice tungro spherical virus--a plant picornavirus. AB - Rice tungro spherical virus (RTSV) was shown to have three coat protein (CP) species by high resolution NaDodSO4-PAGE and Western blot analyses. The sequence of a coat protein-expressing cDNA clone that was identified and selected from a RTSV cDNA library showed that the insert was composed of 2823 bp with only one large open reading frame (ORF) coding for 941 amino acids. The positions of the three coat proteins were located in the putative polyprotein by N-terminal microsequencing and were shown to start at amino acids 287, 495, and 698 for CP 1, CP-2, and CP-3, respectively. The coat proteins are expressed as a polyprotein at the 5' region of the viral RNA genome, and all are cleaved at glutamine carboxy termini, presumably by picornavirus 3C-type of protease(s). Sequence comparisons of coat proteins revealed that there are high amino acid homologies between CP-2 of RTSV and VP3s of encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelitis virus (TMEV). These results indicate that RTSV is a plant picornavirus. PMID- 8367941 TI - Nucleotide sequence of the envelope protein gene of the tick-borne flavivirus, Kumlinge A52. AB - The envelope protein gene of the tick-borne flavivirus, Kumlinge A52, the proto type Finnish strain, has been amplified and sequenced.* The nucleotide and deduced amino acid sequence has been analyzed and compared with the closely related tick-borne encephalitis (TBE) virus, Western subtype, strain Neudoerfl, isolated in Austria. Although these two virus strains were isolated 12 years apart from different hosts and in different countries, the envelope proteins only differed by a single amino acid. It is likely, therefore, that strong selection pressures against antigenic variation exist. The possible reasons for this are discussed. PMID- 8367942 TI - Expression of the "helper component" protein of potato virus Y (PVY) in E. coli: possible involvement of a third protease. AB - Transmission of potyviruses by aphids depends on the presence of a virus encoded helper-component protein (HC) that also exhibits protease activity. HC was expressed in E. coli from two types of clones: a full-length cDNA clone of PVY and two 5' end clones containing the first three cistrons (3.6-3.7 kbp). The clones derived from the 5' end of PVY expressed HC of the size of the mature component. Other proteins reacting with antibodies to HC were also observed, and their sizes corresponded with those of expected intermediates resulting from partial protease cleavage of the three-cistron polyprotein. On the other hand, the only detectable HC-related product of the full-length clone was a mature-size HC. The presence of a third PVY protease among the first three cistrons is therefore suggested. PMID- 8367943 TI - [Reconstructive-restorative operations on the trachea]. PMID- 8367944 TI - [Reconstructive operations on the coronary arteries in ischemic heart disease]. AB - Direct reparative operations on coronary arteries were carried out in 18 patients with ischemic heart disease in order to revascularize the myocardium: auto pericardium plastics of right coronary artery; autogenous vein plastics of the opening and the trunk of left coronary artery; instrumental delactation of opening and the trunk of the left coronary artery; right coronary artery prosthesis and shunt-plastics of the front interventricular branch of the left and right coronary artery. The observation period was from 1 month to 5 years. The article shows the efficiency of direct reparative operations for prophylaxis of myocardial infarctions or sudden deaths. The operated patients also got rid of stenocardia and have acquired a more high tolerance for physical loads. PMID- 8367945 TI - [Angiography in a general military hospital]. PMID- 8367946 TI - [The selection of patients in a therapeutic hospital for the surgical treatment of ischemic heart disease]. PMID- 8367947 TI - [The clinico-functional results of aortocoronary bypass in patients with ischemic heart disease and their medical rehabilitation]. AB - Using the materials of foreign researches the article provides data concerning the modern methods of rehabilitation of cardiological patients taking into account its efficiency for various age groups. Operation on heart itself is a psychological shock to the patient. It needs adequate psychological adaptation and corresponding medical care. 300 patients with ischemic heart disease were under the authors' observation after aortocoronary shunting (age 31-69). Clinical and functional results were studied after operation. The results of early and late loading tests were analysed. Indication for hypolipidemic therapy were determined. The article reports on the errors in determining the proof loads and limitations in the correction of myocardial insufficiency. The authors substantiate the possibilities towards prognostication of the course of ischemic heart disease after operation. PMID- 8367948 TI - [Changes in the central and peripheral hemodynamics of patients with acute peritonitis in the immediate postoperative period]. AB - The article examines hemodynamic indices in patients with acute peritonitis in proximate preoperative period, taking into account etiology of the disease, a period passed from the appearance of illness and up to the performance of operation, and the scope of infusion-transfusion therapy. An algorithm of preoperative volemic preparation was worked out which made it possible to normalize hemodynamic homeostasis in patients and assure the performance of operation in more favourable physiologic conditions. PMID- 8367949 TI - [The use of echocardiography in examining patients with unstable stenocardia]. AB - The report presents the results of EchoCG study in 81 patients with unstable stenocardia admitted in 6-24 hours from the onslaught pain. With the help of EchoCG the myocardial contractile function was defined and the segmental kinetics of left ventricular wall was registered with respect to four variants of unstable stenocardia courses: stenocardia occurred for the first time, progressive stenocardia, variational stenocardia and postmyocardial infarction stenocardia. During the EchoCG examination at the moment of anginal attack the significant increase in left ventricular end-diastolic volume and end-systolic volume and decrease of total ejection fraction were noted. Also, not infrequently the zones of dyskinesia are recorded indicative of ischemia of these segments, which commonly have transient character. With the progress of myocardial ischemia the abnormalities of left ventricular diastolic fraction appear which are determined with the help of Doppler-EchoCG. Thus, the use of EchoCG in diagnostics of patients with unstable stenocardia allows more reliably to define the degree of myocardial changes. PMID- 8367950 TI - [The potentials and outlook for rendering specialized medical care at the N. N. Burdenko Main Military Clinical Hospital. Interview by G. G. Piskunov]. PMID- 8367951 TI - [Newly occurring stenocardia: the clinical picture, diagnosis, treatment and prognosis]. AB - The article analyses the results of treatment of 77 patients with primarily emerged stenocardia. Three variants of clinical course of illness were distinguished: primarily emerged stenocardia at the state of exertion, primarily emerged progressive stenocardia at the state of exertion, primarily emerged stenocardia at rest state. As for primarily emerged stenocardia at the state of exertion, the changes at the final part of QRS complex were disclosed in 56% of patients, and abnormalities in the mobility of the left ventricle walls in 32%. The contractive function of left ventricle was unchanged. The myocardial infarction developed in 8% of patients in the course of one month, and in 4% in the course of one year. Stenocardia attacks disappeared in 16% of patients. As for primarily emerged progressive stenocardia, the ECG changes were marked in 74% of cases. The whole sphygmic fraction in 65% of patients was 55% lower. The myocardial infarction developed in 12% of patients in the course of one month and in 10.7% in more remote period. 52% of patients with the primarily emerged stenocardia at rest had ECG changes. In ECG daily monitoring 33% of patients had characteristic changes of coronary artery spasm. Myocardial infarction occurred in 8% of patients in the course of the first year. Stenocardia attacks disappeared in 25% of patients. PMID- 8367952 TI - [Thrombolytic therapy in acute myocardial infarct and pulmonary artery thromboembolism]. PMID- 8367953 TI - [The efficacy of nitrate solutions in emergency states]. PMID- 8367955 TI - [The clinical picture and treatment of local radiation lesions]. AB - The article gathers a long-term experience in diagnosis and treatment of local radiation injuries in 205 patients, including patients with irradiations caused by accident situation. Relatively good results were obtained during the treatment of severe injuries. PMID- 8367954 TI - [The possibilities of using gastrotsepin in treating digestive organ diseases]. PMID- 8367956 TI - [The early diagnosis of hypoglycemic states with an automatic electronic system]. PMID- 8367957 TI - [The clinical aspects of the early convalescence period in patients who have had viral hepatitis]. PMID- 8367958 TI - [A quarter of a century guarding the health of servicemen]. PMID- 8367959 TI - [The 25th anniversary of the Podmoskov'e Central Military Rest Home]. PMID- 8367960 TI - [The prognosis of the late results of vagotomy and dispensary care in patients with duodenal peptic ulcer]. AB - The article studies the remote results of vagotomy in treatment of 212 servicemen with ulcer of duodenum. Laboratory, endoscopic, roentgenological, pH-metric, manometric, radioimmunological and morphological researches were used before and after operations. From the point of view of prognostication 30 important criteria were selected to forecast the results of vagometry, and also to determine the groups for control examination. These data made it possible to prognosticate the right outcomes of treatment in 84.7% of cases, and thus individualize the treatment and prophylaxis of the prior disease and postvagotomy syndromes reducing their frequency. In the results of these measures the cases of invalidity and disability retirement of servicemen were diminished. PMID- 8367961 TI - The medical assessment of impairment for legal purposes. PMID- 8367962 TI - Recent developments in low-cost screening and assessment of childhood disabilities in Jamaica. Part 2: Assessment. AB - This paper summarises the requirements and criteria for assessment of childhood disabilities. It reviews recent research carried out in Jamaica and outlines procedures for medical and psychological assessment used in the International Epidemiological Study of Childhood Disability as well as local experience in community-based rehabilitation. While the medical assessment procedures were considered to be validated, there is an urgent need for local research and development in psychological assessment. These approaches, while not perfect as yet, bring the possibility of local community capability closer. They will require changes in professional attitudes, training of health and educational personnel, and changes in the service systems, so that screening and assessment can be integrated into existing services. However, although this will obviate the need for new, specialised administrations, improved linkages and lines of referral will be necessary. PMID- 8367963 TI - The nature of interpersonal violence in Jamaica and its strain on the national health system. AB - A random prospective study of 640 victims (76.6% in the 15-39-year-old age group) of interpersonal violence (IPV) at the Kingston Public Hospital was conducted over three months. About 87.5% of the aggression on males and 74.5% on females was committed by males. However, there was more female/female than female/male violence. Weapons used ranged from guns to a variety of cooking wares, though knives were used most frequently (34.8%) for stabbing 48% of the victims. Head, neck and upper limb were the main sites of injury; only 13.4% of all the injured had complications, and 63% of these required hospitalization. Family members and acquaintances contributed to about 84% of the violence. Instinctive spontaneous aggression aimed at maiming the victim characterizes IPV in Jamaica. The Jamaican taxpayer bears 90-94% of the cost of managing trauma injuries. These costs should be recovered from the assailants, even in the form of blood donations and community service. PMID- 8367965 TI - Large loop excision of the transformation zone (LLETZ)--an alternative treatment for cervical intraepithelial neoplasia. AB - The technique of large loop excision of the transformation zone (LLETZ) as an alternative to destructive/ablative methods of treatment of cervical intraepithelial neoplasia (CIN) such as cryotherapy, laser vaporization and cone biopsy of uterine cervix is assessed. Forty-five patients underwent this procedure for either diagnostic or therapeutic reasons. It was well-tolerated, and minor bleeding occurred in 4.4% of patients. The quality of the histological specimen was excellent in all cases, only two showing evidence of charring artefacts. In 11 patients (24.4%), a more serious lesion was detected than that found at punch biopsy of the cervix. This method offers a cheaper and more effective alternative to laser vaporization and combines the benefits of the gold standard cone biopsy of the cervix with that of local ablative techniques. PMID- 8367964 TI - Changes in material resource levels in Jamaica's primary health care services between 1984 and 1991/1992. AB - Jamaica's primary health-care services have been in a process of development since the 1970s. In 1984, a large management study collected data on levels of material resources (basic facilities, utilities, furniture, equipment and supplies items). Since 1984, serious staff shortages have affected the services, and there have been economic constraints, as well as a major hurricane. In order to measure changes over subsequent years, data on material resources were again collected in 1991/1992, using the same sample of 65 types 2 and 3 health centres as in 1984. Data were collected by interview with health centre staff. Results, whilst showing various changes item-by-item, showed constancy or minor improvements overall in levels of resources. Type 2 health centres continued to have lower resource levels than type 3s, even though the methodology allowed for their different needs where appropriate. Staff members' opinions of condition and adequacy of resources had become more positive than before. It was concluded that, in terms of material resources, activities within the primary health-care sector have offset the adverse effects of the macro-environmental conditions affecting the health centres. This method of material resource monitoring has implications for quality assessment of health facilities in primary health-care. PMID- 8367966 TI - Surgery for post-hysterectomy vaginal prolapse. AB - Nine cases treated by surgery for post-hysterectomy vaginal prolapse are reviewed. The mean time between presentation and the antecedent hysterectomy was 12.8 years. Two patients who had abdominal sacral colpopexy alone developed recurrence of prolapse. Additional culdoplasty and colposuspension improved the cure rate but prolonged the mean operating time. Restoration of vaginal anatomy and function is best achieved with the combined operation. PMID- 8367967 TI - Resistance to third-generation cephalosporins in Barbados. AB - Resistance to third-generation, or extended-spectrum, cephalosporins caused by induction of class I beta-lactamases has been reported rarely from developing countries. Seven isolates of cephalosporin-resistant Gram-negative rods were recovered recently from urine, burns and ulcers in the Queen Elizabeth Hospital, Barbados. The isolates were identified as Acinetobacter calcoaceticus (2), Citrobacter freundii (1), Enterobacter cloacae (1), Morganella morganii (1), Providencia stuartii (1) and Proteus sp. (1). Induction of beta-lactamase by cefoxitin was demonstrated, and minimal inhibitory concentrations (MIC) were determined by agar dilution. beta-lactamases were demonstrated by isoelectric focusing; the presence of chromosomal beta-lactamases was confirmed in at least three of the resistant isolates. The only antibiotics which were uniformly active against these resistant strains were imipenem and ciprofloxacin. These data confirm the existence of resistance to the third-generation cephalosporins in Barbados, and emphasise the necessity for continuous surveillance of resistance patterns in the Caribbean region. PMID- 8367968 TI - Analysis of pathogens isolated from urinary tract infections in Barbados. AB - The isolation of pathogens from urine specimens was surveyed during a six-month period when 1611 urine specimens were examined in the Public Health Laboratory, and 8769 were examined in the Microbiology Laboratory of the Queen Elizabeth Hospital. Significant growth (defined as > 10(4) organisms/ml urine) was detected in 393 (24.4%) of the urines cultured in the Public Health Laboratory and in 1218 (13.9%) of urines cultured in the Queen Elizabeth Hospital. The overall isolation rate was 15.5%; Gram-negative bacilli comprised 72.8% of the isolates, Gram positive cocci 24.3% and yeasts 2.9%. Gram-negative bacilli were more commonly isolated from hospital patients, whereas Gram-positive cocci were relatively more common in community patients. The most common pathogens detected were coliforms (1233 isolates), streptococci (197) and coagulase-negative staphylococci (182); 50% of all isolates were sensitive to amoxycillin, 68% to cephradine, 61% to co trimoxazole, 62% to nalidixic acid and 79% to nitrofurantoin. Anti-bacterial activity was detected in 130 (8%) of the urine specimens received in the Public Health Laboratory. PMID- 8367970 TI - Wiskott-Aldrich syndrome in a Jamaican. AB - A 3-week-old boy presented with severe thrombocytopenia and recurrent infections. He was subsequently found to have Wiskott-Aldrich Syndrome, a rare X-linked disorder. Splenectomy was performed and he died of post-splenectomy sepsis despite prophylactic antibiotic therapy. This is the first recorded case in the English-speaking Caribbean. PMID- 8367969 TI - Cushing's syndrome from topical glucocorticoids. AB - A case of Cushing's syndrome is described in a woman who self-treated psoriasis with a variety of potent topical glucocorticoids over 15 years. She was successfully weaned off corticosteroids and was treated with alternative anti psoriatic drugs. The disappearance, nine months later, of most features of Cushing's syndrome, and the normal suppression of cortisol in response to dexamethasone, excluded endogenous hypercorticolism. The apparent widespread availability across the counter of potent corticosteroids is a cause for concern. PMID- 8367971 TI - Co-existing leiomyoma and benign cystic teratoma of the ovary. AB - A case of benign cystic teratoma and a leiomyoma in the same ovary is described. The leiomyoma was confirmed by immunohistochemical methods. The occurrence of leiomyoma and a teratoma within the same ovary is very rare. PMID- 8367973 TI - Reversal of benzodiazepine sedation with flumazenil in a patient with tetanus. AB - A 54-year-old female patient admitted with a diagnosis of tetanus had her sedation reversed with an infusion of flumazenil. Flumazenil appears to be of use in reversal of sedation in patients with accumulation of benzodiazepine after prolonged administration. PMID- 8367972 TI - Necrotizing haemorrhagic colitis caused by resistant Shigella flexneri. Report of a case. AB - A case of fatal infection with Shigella flexneri is reported. The 19-year-old male patient who presented with fulminating haemorrhagic colitis died nine days after the onset of symptoms. The infecting strain of Shigella flexneri was resistant to multiple antimicrobial agents, including amoxycillin, co-trimoxazole and chloramphenicol. PMID- 8367974 TI - Tuberculosis occurrence in CAREC member-countries 1983-1992. PMID- 8367975 TI - Cerebrovascular risk factors in an elderly Austrian population: first year results of the Austrian Stroke Prevention Study (ASPS). AB - During the first year the Austrian Stroke Prevention Study enrolled 599 volunteers without clinical signs or symptoms of cerebrovascular disease aged 50 to 70 years. Study participants were randomly selected from the official register of the city of Graz. The rate of positive response was 26.9 percent. All subjects underwent an extensive risk factor screening with Duplex scanning of the carotid arteries obtained from a subset of 176 individuals. The prevalence of well documented cerebrovascular risk factors was 40.6% for arterial hypertension, 35.4% for cardiac disease, 8.5% for diabetes mellitus und 3% for elevated haematocrit. The less well-documented cerebrovascular risk factors dyslipidemia, overweight, physical inactivity, hyperfibrinogenemia and smoking were noted in 75%, 33.7%, 27.2%, 14.9% and 12.2% of subjects, respectively. Multiple well documented risk factors were noted in 23.7% of the examined volunteers. Multiple linear regression analysis revealed body mass index (p < 0.0001) and age (p < 0.0001) as independent predictors of the frequency of well-documented risk factors observed in any individual. Atherosclerotic carotid disease occurred in 61.9% of study participants investigated by Doppler sonography and was significantly associated with age (p < 0.00001), life-time tobacco consumption (p < 0.0001) and the concentration of apolipoprotein B (p < 0.05). This study demonstrates high prevalence rates of vascular risk factors in an elderly Austrian community. Implications for stroke prevention result from the conjunction of overweight and frequency of risk factors noted in any study participant, as well as from the relationship of carotid atherosclerosis to smoking and dyslipidemia. PMID- 8367976 TI - [Association between fibrinogen and blood sedimentation rate in combined extracorporal and fibrinogen reducing drug therapy]. AB - Fibrinogen appears to play an important role in atherogenesis, whereby high levels of fibrinogen can lead to a disturbance of the haemorheologic pattern. To evaluate the association between fibrinogen and blood sedimentation rate (BSR) 40 patients suffering from cerebral multi-infarct disease underwent a single heparin induced extracorporeal LDL < fibrinogen > precipitation (HELP). Subsequently they were randomly assigned to two groups, either receiving sustained-release bezafibrate 400 mg daily (n = 21) or placebo (n = 19) over a period of eight weeks. HELP led to a statistically significant reduction of fibrinogen (p < 0.0001). At the end of the trial the difference between the bezafibrate group and the controls became significant (p < 0.05). The BSR strictly followed the course of fibrinogen, indicating a significant reduction after HELP (p < 0.0001 for both BSR values) and a difference between both groups at the end of the study (p < 0.05 and p < 0.03, respectively). The correlation between fibrinogen and BSR remained significant during the whole trial. PMID- 8367977 TI - [Serologic detection of Helicobacter pylori antibodies after surgery for stomach and duodenal ulcer]. AB - The occurrence of IgG antibodies to Helicobacter pylori was measured by means of ELISA in 175 patients who had undergone surgery for duodenal or gastric ulcer. There was a significant correlation between surgery with resection and the absence of IgG to Helicobacter pylori in about 80% of cases. In patients undergoing surgery without resection there was no influence of the surgical technique on the presence of Helicobacter pylori antibodies. PMID- 8367978 TI - [Epidemiologic development of AIDS in Austria]. AB - AIDS statistics as released by the Austrian Health Authorities refer to the notification date of the disease, but not the time of diagnosis which is essential for descriptive analysis. We present for the first time data on the exact time of diagnosis of, and death from AIDS. Between 1981 and 1992 altogether 899 AIDS cases were registered (747 men, 152 women), of whom 547 persons have already died (462 men, 85 women). At present there are 352 patients with AIDS in Austria (285 men, 67 women). The incidence, prevalence, and mortality rates of AIDS in Austria, both in absolute and relative (per 100,000 men/women 1990) figures are presented in a table. PMID- 8367979 TI - Evaluation of certain veterinary drug residues in food. Fortieth report of the Joint FAO/WHO Expert Committee on Food Additives. PMID- 8367980 TI - Health promotion in the workplace: alcohol and drug abuse. Report of a WHO Expert Committee. PMID- 8367981 TI - Calcium intake and osteoporosis. PMID- 8367982 TI - Monitoring calcium intake and absorption. PMID- 8367983 TI - Alcohol-induced bone disease. PMID- 8367984 TI - Fluoride and osteoporosis. PMID- 8367985 TI - [Brain sparing autoregulation of fetal circulation in HELLP syndrome- demonstrated by Doppler ultrasound findings]. AB - In a case report of severe placental insufficiency in the HELLP-Syndrome with diastolic reverse flow in aorta and umbilical artery, the changes of flow in the renal artery and middle cerebral artery were demonstrated. A preferential perfusion of fetal brain at the expense of fetal kidneys was shown during fetal hypoxia. PMID- 8367986 TI - [Obstetric management of patients with HELLP syndrome]. AB - The syndrome of haemolysis, elevated liver enzymes and low platelet count (HELLP Syndrome) is a severe form of preeclampsia and eclampsia. The clinical course is characterized by right upper quadrant and epigastric pain, hypertension, proteinuria and edema. Maternal and neonatal morbidity are high. The underlying cause for this pregnancy-related syndrome is still unclear. As soon as a reliable diagnosis is established handling of patients suffering from HELLP-Syndrome is ambivalent: Immediate termination of pregnancy, however, poses a problem at early gestational age. Therefore some authors have advocated a conservative management. At our department active management and delivery by Caesarean section as soon as possible has gained acceptance in the past 5 years. We report our experience with 23 patients over a 12 year period, and with 4 patients from the intensive care unit (N = 27). Mean gestational age was 33.5 weeks (+/- 4.8) and the mean birthweight was 1922.5 g (+/- 971.5). 19 patients were delivered by Caesarean section. Most complications were based on a delayed delivery and subsequent deterioration of maternal condition. Reduction of the time interval between establishment of diagnosis and termination of pregnancy (1980-1985-3 days; 1986 1992-12 hours) resulted in a better outcome. We recommend intensive laboratory screening and exact clinical examination since missed or delayed diagnosis as well as delayed delivery are life threatening for mother and child. Only prompt delivery yields an improvement of prognosis. PMID- 8367987 TI - [Detection of fetal urinary obstructions requiring therapy in routine prenatal ultrasound]. AB - Routine ultrasound during pregnancy is also performed for the detection of fetal malformations. This retrospective study comprises 31 children treated for urinary tract infection within 19 months postnatally. The charts of the young patients were evaluated how often a dilatation of the upper urinary tract (more than 3 cm in diameter) was observed already during pregnancy. In 18 patients (58%) the dilatation was detected antenatally and was missed in 13 (42%). Reasons of the low sensitivity may include low technical standard of the sonographic equipment and limited skill of the investigators. PMID- 8367988 TI - [Uroflowmetry and ultrasound residual urine determination in pregnancy and post partum]. AB - In order to estimate the influence of adaptational processes during pregnancy and post partum on micturition, uroflow-parameters (3) and residual urine were examined in 119 healthy women. Comparisons were made between women in the 1st, 2nd and 3rd trimester of pregnancy, women who were between 1 and 5 days post partum and nonpregnant, fertile women. Compared with the control group the mean flow was significantly lower during the 2. and 3. trimester. Time taken to achieve maximum flow was significantly higher after spontaneous delivery compared with the control group. During pregnancy and after delivery an increase in flow time could be shown. During the 3rd trimester time taken to achieve maximum flow was noticeably higher than in the other groups. Both mean and maximum flow were lower during pregnancy and after spontaneous delivery than in the control group. Residual urine increased mainly during the 1. trimester and showed the highest value after delivery. As all the investigated differences stayed within the standardized values, uroflowmetric investigations and ultrasonic residual urine estimation during pregnancy and after delivery are only necessary if suspicious symptoms on the part of the urinary tract exist. PMID- 8367989 TI - [Histology of chorioamnionitis: relations to maternal and fetal infection parameters]. AB - With regard to clinical diagnosis and prognosis, intrauterine infection continues to pose major problems for obstetricians. In recent years serum assay of CRP, an acute phase protein, has become firmly established in the obstetric management of premature rupture. We investigated the relationship between histologically confirmed chorioamnionitis and maternal and fetal inflammation parameters in 69 patients on the basis of inflammation of the membranes, placenta and cord occurring in histomorphologic stages. Our results show the C-reactive protein to be a sensitive and specific indicator of chorioamnionitis and closely correlated with both the histologic stage and the severity of the chorioamnionitis. We therefore advocate adoption of the histologic result as the "gold standard" for evaluating subclinical and clinically manifest forms of intrauterine infection. PMID- 8367990 TI - [Reference values for plasma amino acids in the course of pregnancy]. AB - Reference values for 26 plasma amino acids were determined by ion exchange chromatography in 29 healthy pregnant women (1st to 3rd trimenon). The results are given as P50 (P7-P93). In the course of pregnancy the concentrations of amino acids generally decrease. Threonine, however, shows a distinct, statistically significant increase. The interindividual concentration ranges are low and they show little change in the course of pregnancy. The data presented here are relevant for dietary treatment of metabolic disorders, e.g. maternal phenylketonuria in pregnants. PMID- 8367991 TI - [pH-metry in vivo--use in obstetrics]. AB - A new equipment and technique in order to analyse the pH in vivo will be presented. The special rod-shaped probe contains an ISFET pH sensor. There is pointed out a wide field of applications in the obstetrics. PMID- 8367992 TI - [Health diagnosis and health counseling. Traditional risk factors are not in the foreground!]. AB - This article reviews the bio-psycho-social factors of health stabilization and health rehabilitation. It is our aim to improve psychology's and general medicine's cooperation in these fields of research and practice. We, therefore, firstly concentrate on the psychosocial factors which improve health diagnosing and health education; we illustrate health education by selectively reviewing illness-related health trainings. Secondly, we discuss health counseling. Again, we concentrate on the improvement of general practitioner's health counseling. On the one hand, this improvement seems possible on the basis of individual bio psycho-social risk models. Individual bio-psycho-social risk models, on the other hand, only can serve as a basis for individual-centered interventions, but not for population-centered interventions. After reporting various case histories from different doctor-patient-interactions, we demonstrate the application of bio psycho-social risk models in the individual case. These applications in the general practitioner's office promise to be useful. Nevertheless, general medicine as well as psychology seem to have only minor interest in intensifying their cooperation. PMID- 8367993 TI - [Suicidality in thinking and experience of children and adolescents]. AB - In researching the tendency to suicide among children and adolescents it is important to know what they think about the attitude towards suicide. The present article covers a survey taken of 465 male and female pupils on this subject. On the one hand it reveals some interesting differences in the results according to age groups and sex, but on the other hand thoughts of suicide expressed by the younger pupils questioned are not significantly lower than those expressed by older pupils. This result seems noteworthy because the rate of suicide in youths increases with age. PMID- 8367994 TI - [Legal discussion on euthanasia of severely ill patients from the medical viewpoint]. AB - Demographic factors lead to rising numbers of old and very old people in our society. In connection with this development the numbers of the seriously ill and handicapped needing comprehensive care are growing. Society is not sufficiently prepared to meet these ethical and economical problems. In this situation consequentialistic utilitarism may contribute to the social acceptance of direct, active euthanasia. Three paradigmatic judicial cases are described. Medical aspects of recent discussions in the field of criminal law are given. The danger of the "bursting of the dam", i.e. the tolerance of killing incurably ill and old patients is stressed. Compassion, self-determination, and economical considerations can not be accepted as reasons for the killing of human beings. PMID- 8367996 TI - [Detection of meta-syndromes in configuration frequency analysis]. AB - Metasyndromes are defined as combinations of two or more single syndromes. A statistical method for ascertaining their existence on the basis of observational data is given. This is an improvement over another technique previously presented in this journal. PMID- 8367995 TI - [What is therapeutic in psychotherapy? An empirical evaluation of assumptions of the "Generic model of psychotherapy"]. AB - What is effectively therapeutic about psychotherapy? The generic of psychotherapy provides an empirically valid conceptual representation of psychotherapy process and outcome relationships that begins to answer this question. The aim of this study is an empirical investigation of patterns of process and outcome relationships. The data come from 18 single therapies (9 very successful and 9 less successful therapies) of the Bernese Comparative Treatment Study (Grawe, Caspar & Ambuhl, 1990). First the variables of the generic model of psychotherapy are operationalized by different process and outcome measures. The statistical method of stepwise multiple hierarchical regression serves to prove a number of assumed relationships of the generic model. The findings reported here demonstrate the utility of the generic model for guiding exploratory psychotherapy research that aims to identify emerging patterns of relationships between process and outcome. PMID- 8367997 TI - [The architecture of the brain and the individuality of personality (formulating the problem)]. AB - The article is concerned the problem of comparison of the individual psychophysiological characteristics (human personality) with structural peculiarities of human brain. The importance of such analysis of personal individuality is underlined. The author undertakes an attempt to consider some personal individuality in the light of the his postulated systemic principles of the brain structure-functional organization. The examples of possible comparison of the some human abilities with the structural signs of their brain have been done. These abilities can be obviously reflected in the different variations of the cortex and subcortical structures construction. The author premises his ideas to the following publication of the article-essay "The study of Lenin's brain". PMID- 8367998 TI - [Academician Aleksandr Mikhailovich Ugolev. The development of his scientific ideas]. AB - The science suffered a severe loss with the sudden death in November 2, 1991, of and outstanding physiologist Academician Alexander Mikhailovich Ugolev at the age of 66. All life of this man was devoted to the development of the national science. It was the aim and meaning of his life, he has contributed to scientific progress in every possible way. The major scientific interests of A. M. Ugolev were focused on the basic and applied areas of food assimilation, including the physiology of nutrition and digestion. The works of the scientist in this field of knowledge were world-wide recognized. During his scientific activity Dr. Ugolev conducted a number of brilliant studies which remained unforgettable trace in physiology and for ever will be a part of golden fund of science. This was promoted by a unique combination of his illustrious abilities of physiologist and general biologist as well as evolutionist with the gift of experimenter and excellent surgeon. His experimental skill can serve and example of an elegant combination of bold intentions and their masterly realizations. But the most remarkable and world-wide recognized discovery of the scientist was that of membrane digestion--previously unknown mechanism of food assimilation. Just this basic discovery is emphasized in the review devoted to the memory of unforgettable master. The fragmentariness of material depends on a desire to present concisely the major characteristics of membrane digestion. PMID- 8367999 TI - [The study of V. I. Lenin's brain]. AB - The investigation of V. I. Lenin's brain was carried out on the basis of study of 1108 cytoarchitectonical slices (thickness of 20 mu), stained by Kresil-Violett (Nissl's method) and 558 slices of fibres stained by Geidenhain's method. This is the first in the history of science detailed microscopical study of the man brain, initiated to creation of russian architectonics (as a science of the brain architecture); this study was served for a foundation of structural basis of science on the brain individual variability of different people including prominent persons. The results of this study is compared with a data of the later macroscopic and microscopic investigation of many persons brain with different professions and abilities. The next peculiarities of the Lenin's brain have been written: 1. The relief complexity and peculiarities of sulci and gyri configuration, especially in frontal lobe. 2. The big percentage of the cortex in a deep of the sulci (so called intrasulcal component), and as a result of the increasing of the summarised size of the cortex cerebri. 3. The riches and pronunciation of s.c. limitrophic adaptation's zones between different areas, especially in the frontal lobe and in the other associative cortical structures. 4. The originality in relation in size between area in one region and regarding to the whole cortex surface. The prevail of the size and variability of phylogenetically new (associative) regions, especially of frontal one (which takes part in the function of situation estimation, prognostication, generalization) and also of parietal and temporal cortex; the phylogenetically old zone are more stable. 5. The large number of the especially big pyramidal neurons in sublayer III (III(3)), that can be supposedly looked as a structural basis of the rich associative connections between different cortical regions. The above mentioned peculiarities have been done as a result of the study chiefly of the right brain hemisphere because the left one was seriously suffered as a result of the vessels damage of atherosclerosis origin. PMID- 8368000 TI - [The systems organization of behavior: novelty as the leading factor in the expression of early genes in the brain during learning]. AB - The paper deals with the analysis of the systemic mechanisms underlying behavioral activation of the family of "Immediate Early Genes" in the animal brain. These genes are the first element of genetic mechanism that starts in the cells the long-term rearrangements of transcription in response to different extracellular effects. Previously it was shown that this mechanism is involved in the processes of initiation of the cell growth and differentiation. The experimental findings of this paper demonstrated that the induction of "Immediate Early Genes" genes c-fos, c-jun and zif/286 occurs in the nervous system of various animal species in the situations of learning and environmental novelty. Activation of "Immediate Early Genes" expression is noted in the nerve cells of the numerous structures of the brain and is of systemic character. Housing of the animals in usual living conditions and using by them previously acquired habits do not result in an increased expression of these genes. On the basis of the analysis of behavioral conditions of the activation of "Immediate Early Genes" it is supposed that the critical factor of firing this genetic mechanism is a subjective "novelty" of behavioral situations for animal, i. e., initiation of mismatch of the behaviour with the acceptors of the results of an effect of the early formed functional systems. PMID- 8368001 TI - [Peptidergic mechanisms in the parasympathetic regulation of the heart rate]. AB - Besides the classic cholinergic and adrenergic mechanisms, the regulatory peptides involve in regulating the cardiac rhythm. The localization of the latter in neurons of intracardiac nervous system as well as the possibility of releasing the regulatory peptides, individually or in combination with the classic mediators, during extracardiac nerves is found. The regulatory peptides are capable of affecting the heart autonomy directly or in a mediated way via modulation of the vegetative effects. The paper contains data on the cardiotropic activity of various peptides and direction of their effects relating to parasympathetic control a cardiac rhythm. There is a suggestion concerning an existence of different ways of realization of peptidergic vagotropic effect that presupposes not only variation of severity of parasympathetic chronotropic effect but also a change in its functional organization. PMID- 8368002 TI - [The current problems of studying the systems morphophysiological mechanisms of animal growth]. AB - The study of general physiological mechanisms of the growth in highly important for the substantiation of the general strategy and the choice of practical methods of animal growth regulation. A shortcoming of many phenomenological growth theories lie in the fact that they don't take into consideration the key role of the processes of cellular proliferation and of histo and organogenesis. On the basis of bibliographic and original experimental data a morphofunctional conception of growth is considered. It is supposed that the main links in body growth are the processes of cartilaginous cells division in zones of longitudinal bone growth and of muscle fibers nuclei reproduction. The use of simulation models for study of dynamics of correlation in the system of organs and tissues development is argued. PMID- 8368003 TI - How many yeast genes code for membrane-spanning proteins? PMID- 8368004 TI - Molecular characterization of the SEC1 gene of Saccharomyces cerevisiae: subcellular distribution of a protein required for yeast protein secretion. AB - Strains of Saccharomyces cerevisiae harbouring temperature-sensitive mutations in the SEC1 and SEC5 genes exhibit an accumulation of post-Golgi secretory vesicles at 37 degrees C. We have cloned a fragment of yeast DNA which carries two distinct genes, one of which complements a sec1 mutation, and the other a sec5 mutation. Genetic test confirm that the sec1-complementing gene is indeed SEC1, and is essential for cell growth. Nucleotide sequence analysis reveals that the cloned SEC1 gene is the same as a previously sequenced sec1-complementing gene. The SEC1 sequence encodes a protein of 724 amino acids with a predicted molecular mass of 83 kDa. Antibodies purified from a polyclonal antiserum raised against the protein product of the cloned gene recognize a yeast protein of apparent molecular mass 78 kDa which is found in a detergent-resistant association with a rapidly sedimenting yeast subcellular fraction, behaviour which is suggestive of an interaction with a component of the yeast cytoskeleton. PMID- 8368005 TI - Vectors for the inducible overexpression of glutathione S-transferase fusion proteins in yeast. AB - A rapid and convenient method of protein purification involves creating a fusion protein with glutathione S-transferase (GST) (Smith and Johnson, Gene 67, 31-40, 1988). In this report, we describe two vectors for the conditional expression of GST fusions in Saccharomyces cerevisiae. The parent plasmid is based on a high copy, galactose-inducible shuttle vector previously described (Baldari et al., EMBO J. 6, 229-243, 1987). We have demonstrated the use of this system by creating fusions between GST and the yeast RAS2 gene. GST-Ras2 fusion proteins undergo the post-translational modifications required for Ras2p to become membrane localized. These vectors provide a useful system for the expression and purification of eukaryotic proteins requiring post-translational modification. PMID- 8368006 TI - Isolation of single yeast cells by optical trapping. AB - Individual yeast cells can be successfully isolated and recultured on plates with a new isolation method making use of optical trapping with infrared laser light. The cells can be selected on morphological criteria by high resolution microscopy. The isolation device is constructed from two coverslips separated by spacers, in which selected cells are transferred to a plastic capillary, using the optical trap. To test the procedure, selection experiments were done with a mixture of two Saccharomyces cerevisiae strains, distinguishable both in fluorescence microscopy and on agar plates. These experiments showed that only selected cells were isolated, and close to 100% of the isolated stationary-phase cells formed colonies on agar plates, indicating a high recovery. A lower recovery was obtained with exponential-phase cells, possibly because of a higher sensitivity to laser irradiation. Applications for this method may include the isolation of mutants with altered morphology and the isolation of subpopulations of yeast cultures, for their separate investigation or for the initiation of pure cultures. PMID- 8368007 TI - The in vitro permeability of yeast peroxisomal membranes is caused by a 31 kDa integral membrane protein. AB - A major 31 kDa integral peroxisomal membrane protein (PMP31) of Hansenula polymorpha was purified to homogeneity from isolated peroxisomal membranes by FPLC after solubilization by Triton X-100. Biochemical analysis indicated that this protein, which showed cross-reactivity with antibodies against the 31 kDa porin of the mitochondrial outer membrane of Saccharomyces cerevisiae, had pore forming properties. Firstly, proteoliposomes composed of asolectin and purified PMP31 showed selective permeability, determined as the [14C]sucrose/[3H]dextran leakage ratios. Furthermore, the generation of a delta psi by potassium diffusion gradients was negatively affected by the presence of PMP31 in asolectin liposomes. A similar effect was observed in proteoliposomes containing purified cytochrome c oxidase as a delta psi generating system. Control experiments confirmed that the observed leakage is significant and introduced by the incorporation of PMP31 protein. Selective sucrose leakage was abolished in samples pretreated with glutaraldehyde; an identical effect of glutaraldehyde was, however, not observed for the membrane potential measurements. PMID- 8368008 TI - A comparative study on the transport of L(-)malic acid and other short-chain carboxylic acids in the yeast Candida utilis: evidence for a general organic acid permease. AB - Cells of the yeast Candida utilis grown in medium with short-chain mono-, di- or tricarboxylic acids transported L(-)malic acid by two transport systems at pH 3.0. Results indicate that probably a proton symport for the ionized form of the acid and a facilitated diffusion for the undissociated form were present. Dicarboxylic acids such as succinic, fumaric, oxaloacetic and alpha-ketoglutaric acids were competitive inhibitors of the malic acid for the high-affinity system, suggesting that these acids used the same transport system. In turn, competitive inhibition uptake studies of labelled carboxylic acid in the low-affinity range indicated that this system was non-specific and able to accept not only carboxylic (mono-, di- or tri-) acids but also some amino acids. Additionally, under the same growth conditions, C. utilis produced two mediated transport systems for lactic acid: a proton symport for the anionic form which appeared to be a common monocarboxylate carrier and a facilitated diffusion system for the undissociated acid displaying a substrate specificity similar to that observed for the low-affinity dicarboxylic acid transport. The mediated carboxylic acid transport systems were inducible and subjected to repression by glucose. In glucose-grown cells the undissociated dicarboxylic acids entered the cells slowly by simple diffusion. Repressed glucose-grown cells were only able to produce both transport systems if an inducer, at low concentration (0.5%, w/v), was present during starvation in buffer. This process was inhibited by the presence of cycloheximide indicating that induction requires de novo protein synthesis. If a higher acid concentration was used, only the low-affinity transport system was detectable, showing that the high-affinity system was also repressed by high concentrations of the inducer. PMID- 8368009 TI - TA-repeat microsatellites are closely associated with ARS consensus sequences in yeast chromosome III. AB - Microsatellites are repeats of very short sequences of DNA, interspersed in the genome. In this paper, the occurrence of the two-base repeat microsatellites has been investigated in the DNA sequence of yeast chromosome III. Only AT-repeats were found at a significantly high frequency. Some of the regions with the highest concentration of AT-repeats were located and further analysed, showing a close association with the core consensus of autonomously replicating sequences. PMID- 8368010 TI - Different signals control the activation of glycolysis in the yeast Saccharomyces cerevisiae. AB - The glycolytic pathway in Saccharomyces cerevisiae is activated by fermentable sugars at several steps. Mutants with deletions of genes coding for enzymes of the upper part of glycolysis were used to characterize the triggering mechanisms. Synthesis of fructose-2,6-bisphophate is catalysed by two 6-phosphofructo-2 kinase isoenzymes, one of which is activated by fermentable sugars while synthesis of the second enzyme is induced (Kretschmer and Fraenkel, 1991). Increase in the level of fructose-2,6-bisphosphate is demonstrated to depend on an internal metabolite upstream of the phosphoglucose isomerase reaction. The signalling process correlates with distinct temporal changes in the concentration of glucose-6-phosphate but not with its absolute level, indicating an adaptational mechanism. It is independent of the uptake and phosphorylation systems used by different sugars. Interestingly, this increase, although delayed, could also be observed in strains lacking the rapid cAMP increase after sugar addition which is thought to be responsible for the activating process. Synthesis of glucose-6-P and fructose-6-P is needed for the complete induction of pyruvate kinase and inactivation of fructose-1,6-bisphosphatase. On the other hand, induction of pyruvate decarboxylase depends mainly on a signal in the lower part of glycolysis. PMID- 8368011 TI - Cloning and sequencing of the Saccharomyces cerevisiae gene LYP1 coding for a lysine-specific permease. AB - The LYP1 gene of Saccharomyces cerevisiae was cloned by complementation in lysine permease-deficient recipient yeast cells, and its nucleotide sequence was determined. An open reading frame of 1833 nucleotides was found encoding a polypeptide of 611 amino acids, with a calculated molecular weight of 68 118. Analysis of the deduced primary structure of the protein revealed ten membrane spanning regions and three potential N-glycosylation sites. Analysis of the deduced sequence of protein LYP1 indicates homology with other yeast amino-acid permeases, in particular with CAN1, and also the lysine-specific permease of Escherichia coli. The strain transformed by a multi-copy plasmid harbouring the LYP1 gene, showed a 20-fold increase in the maximum velocity of lysine uptake over that in the wild type, with no changes in the affinity of the permease for its substrate. PMID- 8368012 TI - Vector YFRp1 allows transformant selection in Saccharomyces cerevisiae via resistance to formaldehyde. AB - Formaldehyde (FA), a chemical with low toxic potential, is used as sole selective agent for transformation in the yeast Saccharomyces cerevisiae. Neither stable auxotrophic markers in recipient cells nor defined synthetic media are needed when multicopy vector YFRp1, containing the yeast SFA gene, is employed for yeast transformation. The SFA gene gives stability to the vector and its yeast (and other) passenger genes when transformants are propagated in complex media supplemented with 3-5 mM-FA. Use of inexpensive FA and non-synthetic, undefined media will lower the cost of yeast transformant propagation considerably and thus make feasible large-volume industrial application of transformants containing YFRp1 derivatives. PMID- 8368013 TI - Regulation of glycolytic enzymes and the Crabtree effect in galactose-limited continuous cultures of Saccharomyces cerevisiae. AB - In order to determine whether the changes in the activities and mRNA levels of enzymes involved in intermediary carbon metabolism previously observed in glucose limited continuous cultures (Sierkstra et al., 1992a) were glucose specific, we have analysed their regulation in a galactose-limited continuous culture of Saccharomyces cerevisiae. The Vmax of the galactose uptake system was shown to be dilution rate (D) dependent, comparable with the high-affinity glucose uptake. The maximum uptake was observed at D 0.2 h-1 (0.25 mmol min-1 per g) and the minimum uptake (0.1 mmol min-1 per g) at D 0.05 h-1 and 0.3 h-1. The aerobic fermentation of galactose occurred at D 0.275-0.3 h-1 which is identical to the results obtained in glucose-limited continuous cultures of this strain. Because galactose is not a repressing carbon source, this demonstrates that the Crabtree effect is not mediated by, or in any way related to glucose repression. Moreover, invertase and hexokinase I mRNA levels (both subject to glucose repression at the transcriptional level) were present when the yeast produced ethanol in galactose- and glucose-limited continuous cultures. In glucose-limited continuous cultures a decrease in alcohol dehydrogenase (I and II) mRNA levels and activity and phosphoglucomutase activity was observed with increasing dilution rates. In addition, at D 0.3 h-1, when the yeast produced ethanol, glucose-6-phosphate dehydrogenase and pyruvate decarboxylase were induced and a decrease in respiration was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368015 TI - Current awareness on yeast. PMID- 8368014 TI - A 12.8 kb segment, on the right arm of chromosome II from Saccharomyces cerevisiae including part of the DUR1,2 gene, contains five putative new genes. AB - A 12,820 bp fragment from the right arm of chromosome II of Saccharomyces cerevisiae was sequenced and analysed. This fragment contains six non-overlapping long open reading frames (ORFs) designated from the centromere- to the telomere proximal ends as: YBR1441, 1443, 1444, 1445, 1446 and 1448. YBR1441 encodes a polypeptide of 845 amino acids which shares a long consensus domain with products of S. cerevisiae MCM2, MCM3, CDC46 and Schizosaccharomyces pombe cdc21+ genes. These genes are involved in DNA replication. YBR1445 encodes a polypeptide of 404 amino acids which has strong similarity with the S. cerevisiae KRE2/MNT1, YUR1, KTR1 gene products. The KRE2/MNT1 protein is an alpha-1,2- mannosyltransferase. The product of YBR1444, which encodes a protein of 375 amino acids, presents a lipase signature sequence and a peroxisomal targeting signal. YBR1448, whose sequence extends further on the telomere-proximal end of the fragment, is identical to the 3' end of the DUR1,2 gene encoding urea amidolyase. The two ORFs, YBR1443 and YBR1446, exhibit no significant similarity with any known gene. PMID- 8368016 TI - [Therapy of rheumatoid arthritis with azathioprine--results of an open long-term study of at least 4 years with 528 patients]. AB - In an open study 528 patients affected with rheumatoid-arthritis were treated with azathioprine, then observed for a period of at least 4 years and assessed according to Steinbrocker's therapeutic criteria. In 178 of them (33.7%) the therapy was still effective even after that time, which corresponds to grade I and II according to Steinbrocker. The therapy was cancelled in 211 patients due to ineffectiveness and in 85 patients due to side-effects. The side-effects are represented in detail. Owing to the favorable relationship between benefit and risk, azathioprine proves to be a means of first choice in all cases with a high process activity and an unfavorable prognosis. PMID- 8368017 TI - [Follow-up of rheumatoid arthritis beginning in advanced age]. AB - Two cohorts of 125 patients each, with different onset of disease (group A = before the age of 55, group B = after the age of 54) were selected from a total of 1000 patients with definite rheumatoid arthritis (RA). Both groups were identical with regard to gender (women = 71%) and duration of disease (mean = 7 years). Mean age was in group A = 47, in group B = 68 years, respectively. When compared, in both samples no significant differences were found with regard to acuity of onset, to occurrence and duration of a period with nonspecific complaints prior to synovitis and to incidence of remissions and fever. However, in the elderly onset group progression of disease was significantly higher, the functional status poorer, dynamometer values lower, and the frequency of systemic signs higher. Furthermore, in the late onset group were more rarely reported regular exercise programs, other rehabilitative measures, treatment with gold preparations, and joint surgery. These features seem to indicate that age at onset has a modifying effect on disease expression in RA. One factor of influence, among others, is likely to be the generally decreased functional level in higher age. Late onset RA is not thought to be a separate entity of the disease. PMID- 8368019 TI - [Disorders of proprioception of the arthrotic knee joint]. AB - We measured proprioception of the knee joint by an active and a passive method in 40 subjects under 30 years of age and in 80 subjects older than 50 years with no evidence of knee joint disease. Joint position sense was also determined in an additional 59 patients with osteoarthrosis of the knee. Proprioception was found to decline with increasing age. In the osteoarthritic knee the measured values were significantly higher than in both groups without knee-joint involvement. An elastic bandage had a positive effect. There was a positive correlation between proprioception and clinical parameters. Walking ability and range of motion did not significantly influence the proprioception. Patients receiving physical therapy showed an improved joint position sense. PMID- 8368018 TI - [Chronic recurrent polychondritis]. AB - Relapsing polychondritis (RP) is a recurrent, chronic und rare disease of unknown etiology, characterized by inflammation of cartilaginous structures of the ears, nose, respiratory tract and joints. The association with HLA-DR4 and the occurrence of antibodies to type-II collagen and other autoantibodies suggest that an immunologic mechanism is involved in its pathogenesis. In about 30% of occurrences RP is associated with other rheumatic or autoimmune diseases. Ocular inflammation, involvement of the cardiovascular system, skin, central nervous system and audiovestibular organ are most probably caused by vasculitis. The course of RP is variable. Severity and outcome primarily depend on the occurrence of associated autoimmune diseases and vasculitis. According to the activity and systemic manifestations, medical treatment includes nonsteroidal antiinflammatory drugs, corticosteroids and cytotoxic agents. PMID- 8368020 TI - [Ultrasound study of the elbow joint in patients with chronic inflammatory joint diseases--an enrichment of diagnosis?]. AB - After clinical and radiological examination, the elbows of 74 patients with rheumatoid arthritis were examined by ultrasound. Clinical examination gives a good impression of the inflammatory changes of the elbow joint. Sonography was very useful in detecting synovitis and joint effusion and their distribution in the different parts of the joint. It is a good method to document the therapeutic effects; therefore, beside the clinical and radiological findings ultrasound may be helpful in planning further therapeutic measures for the patient. PMID- 8368021 TI - [Clinical use of magnification radiography in rheumatologic differential diagnosis]. AB - Rheumatologic joint disorders were examined with high-definition microfocal magnification radiography. The magnification technique was compared to conventional radiographs (mammographic film-screen combinations). The microfocal x-ray unit had a spot size of 20-130 microns. Fourty patients with early arthritis (history of less than 18 months) were examined; x5 magnification was used. Digital luminescence radiography was employed to minimize radiation dose. Digital image processing included simulation of conventional technique and edge enhancement. Magnification radiographs and conventional technique were evaluated. In 20/40 patients articular lesions were detected. Magnification radiography gave additional information in 14/20 patients: in 5/14 patients lesions were seen only with magnification radiography (erosions n = 3, loss of the cortical white line n = 2), in 9/14 patients the extent of the lesions could be evaluated better. Hence, magnification radiography proved a valuable mean in early diagnosing and evaluating rheumatic disease. PMID- 8368022 TI - [Possibilities and relevance of three-dimensional reconstruction of the sacroiliac joint]. AB - The sacroiliacal joint is difficult to evaluate clinically due to its complex form and its topographical position, deep in the body and surrounded by other skeletal structures. We evaluated the potential role of three-dimensional reconstruction and segmentation of CT data of this joint. A total of five patients were examined (age range 24-60 years). In three of these only surface reconstructions were obtained; in the other two, segmentation was obtained as well in order to directly visualize the joints surfaces of the sacroiliacal joint. Compared to conventional radiographs and standard CT, three-dimensional reconstruction and segmentation of the sacroiliac joint did not add significant information. The subtle skeletal findings occurring in inflammatory and degenerative disease were obscured by the process of segmentation. Therefore, radiographs and, in selected cases, CT remain the imaging methods of choice for the evaluation of sacroiliac pathology. PMID- 8368023 TI - [Potential effects of nutrition including additives on healthy and arthrotic joints. I. Basic dietary constituents]. AB - Owing to the methodological difficulties involved, none of the studies so far published on the influence of diet on human osteo-arthritis has been fully comprehensive. We have therefore compiled a series of experimental observations- including some of our own--in the mouse and other species that have a bearing on this subject. Fats with a high content of saturated fatty acids, such as pork fat, greatly favored the development of spontaneous osteo-arthritis in the mouse, as also did cholesterol. Cottonseed oil and olive oil showed less tendency to do so. The highly unsaturated linoleic acid antagonized the effect of pork fat. Other vegetable oils and also fish oil exerted an anti-inflammatory and antinociceptive action in experimental animals. Foodstuffs rich in carbohydrates only promoted the development of degenerative joint disease in predisposed mice. Hyperglycemia (diabetes mellitus) constitutes a risk factor for the development of osteo-arthritis in humans as well as in mice and rats. A low-protein diet led to dysplasia of the hip joint in the dog; a high-protein diet inhibited the development of osteo-arthritis in the mouse, but promoted inflammation in volunteers. Disturbances of protein metabolism such as alkaptonuria can initiate degenerative processes in the joints of humans and animals. PMID- 8368024 TI - Study of the photochemical immobilization of alkaline proteinase and chymotrypsin on the solid phase of O-hydroxyethylcellulose. AB - Stability of the photochemically immobilized alkaline proteinase (E.C. 3.4.21.14) and chymotrypsin (E.C. 3.4.21.1.) onto the gel of O-hydroxyethylcellulose has been studied. For the purpose of immobilization the photochemical generation of nitrene radicals caused by the photolysis of an azido group of bifunctional 4,4' bis-azidostilbene-2,2'-disodium-sulphate and the newly synthetized O-(3 azidophthaloyl)-O-hydroxyethylcellulose have been employed. The immobilized alkaline proteinase demonstrated a decreased ability of denaturation and an increased laboratory stability. PMID- 8368025 TI - Mycoflora and natural occurrence of mycotoxins in tobacco from cigarettes in Egypt. AB - Forty-two species and 4 varieties belonging to 21 genera were collected from 40 tobacco samples on glucose- and cellulose-Czapek's agar at 28 degrees C and 45 degrees C. The most common mesophiles (at 28 degrees C) in tobacco on the two types of media were: Aspergillus flavus, A. flavus var. columnaris, A. fumigatus, A. niger, Penicillium chrysogenum and P. funiculosum. Two samples were heavily contaminated with members of Fusarium (F. moniliforme, F. oxysporum, F. solani). Some fungi were encountered only on plates of cellulose agar as Chaetomium globosum, Stachybotrys atra var. microspora and S. chartarum. At 45 degrees C the most prevalent fungus was A. fumigatus. Truely thermophiles were also collected: Humicola grisea var. thermoidae, Rhizomucor pusillus and Thermoascus aurantiacus. Based on biological assays (brine shrimp larvae (Artemia salina L.) and Bacillus megatherium test) and chemical analysis of chloroform extraction of tobacco (TLC and UV spectrophotometric), four samples (out of 40) had toxicity and four compounds of mycotoxins were detected namely; aflatoxins B1 & B2 (2 samples; 15.5 and 20.7 micrograms/kg), zearalenone (1 sample, 5.5 micrograms) and T-2 toxin (1 sample, 2.8 micrograms). For studying the tracing of aflatoxins in smoking cigarettes, three doses (10, 20 and 50 micrograms) of aflatoxins B1 and B2 (w/w, 1:1) were injected each in ten cigarettes. All extracts of cigarettes smoke proved to be non-toxic and mycotoxins not detected. However, aflatoxins were detected in topping filter (2.8, 3.5 and 8.8 micrograms/the three doses, respectively). PMID- 8368026 TI - Cellulase production on high levels of cellulose and corn steep liquor. AB - Several enhanced cellulase mutants of Trichoderma reesei have been used for cellulase production using corn steep liquor and microcrystalline cellulose as substrates. Under the optimum fermentation conditions on 6% cellulose and 3.6% corn steep liquor Trichoderma reesei Rut C 30 produced high levels of cellulase enzymes 6MC-ase 54 IU/ml, filter paper activity 3.2 IU/ml after 10 days incubation at 28-30 degrees C. PMID- 8368027 TI - Terrestrial fungi inhabiting certain species of Nile fishes in Egypt. AB - Twenty specimens of six species of Nile fishes were examined for the presence of fungi. Of which 2 were from Alestes nurse; 3 from Bagrus docmac; 4 from Barbus bynni; 6 from Chrysichthys auratus; 4 from Lates niloticus and 1 from Malapterurus electricus. Forty-three fungal species in addition to 1 variety appertaining to fifteen genera were recovered from skin (15 genera and 34 species + 1 variety); gills, kidney (12 genera and 30 species + 1 variety, each); liver (11 genera and 30 species + 1 variety) and intestine (13 genera and 30 species + 1 variety) of all specimens, using glucose Czapek-Dox medium at 28 degrees C. The most common genera were Aspergillus, Penicillium and Trichoderma. PMID- 8368028 TI - Physiological studies on xylanase production by Penicillium funiculosum on some agricultural wastes. AB - Studies were carried out on production of Xylanase enzyme from P. funiculosum NRCE-629 using a number of alkali-treated lignocellulosic wastes as carbon and energy sources as compared to pure xylan polymer. Sugar cane bagasse, rice straw and wheat straw yielded enzyme levels higher than that obtained on pure xylan. Physiological studies on enzyme formation using those three agricultural wastes revealed that optimum enzyme yields are obtained in media containing 2% substrate concentration. The enzyme synthesis was favored in agitated cultures with an air:medium ratio corresponding to 3:2 respectively with inoculum size of 10% (v/v). Further studies using rice straw medium yielded highest enzyme level after five days of aerobic growth at 30 degrees C with initial pH of medium adjusted to 5.0. Results are discussed in the light of possible application. PMID- 8368029 TI - [Do drugs in pregnancy modify neonatal jaundice?]. AB - An increased incidence of neonatal jaundice has been observed in babies born to mothers who were treated with different drugs before or during delivery. In this review literature data on such drugs are collected which are under suspicion to produce increased levels of bilirubin in the newborn infant. Despite numerous attempts to show significant effects of these drugs on neonatal hyperbilirubinaemia most of them give contradictory results. Nevertheless, agents that stimulate uterine motility (oxytocin) as well as drugs that inhibit uterine motility (ritodrine) may have an icterogenic effect. Possible mechanisms of their actions are described. Thus, even if there is some association between drugs given prenatally and jaundice developing postnatally, no practical consequences arise except in such cases where additional risk factors may increase the danger of bilirubin encephalopathies in jaundiced infants. PMID- 8368030 TI - Semiquantitative determination of IL-1 alpha, TNF-alpha, PDGF-A, PDGF-B, and PDGF receptor in term human placenta using polymerase chain reaction (PCR). AB - Eight placenta samples derived from normal term human placenta were examined for the expression levels of Il-1 alpha+, TNF-alpha+, PDGF-A+, PDGF-B+, and PDGF receptor+ using a semiquantitative PCR protocol. The expressional level of beta actin was proven to be constant, therefore beta-actin could serve to equilibrate sample size in our procedure. Differences were found in the mRNA levels of IL-1 alpha and TNF-alpha. The expression of PDGF-A, BDGF-B and PDGF-R seemed to be relatively constant in our group of samples. Further investigation and improved quantitative PCR protocols are needed to correlate clinical outcome of pregnancy with cytokine expression at the placental level. +Il-1 alpha (interleukin-1 alpha) +TNF-alpha (tumor necrosis factor-alpha) +PDGF-A (platelet derived growth factor A) +PDGF-B (platelet derived growth factor B) +PDGF-Rezeptor (platelet derived growth factor-rezeptor). PMID- 8368031 TI - [Proteolytic enzymes in meconium--studies of healthy newborn infants and premature infants]. AB - Peptidatic activity of meconium of 200 newborns and 100 preterm babies. Protein content of meconium is higher in preterm babies than in healthy newborns referred to fresh weight. Enzymatic activity opposite to Gly-D-Leu is higher in term than in preterm newborns. It is on the contrary in the case of alanine-aminopeptidase, dipeptidyl-peptidase IV and the activities opposite to Leu-NA and Arg-NA. The good correlated enzymatic activities opposite the different substances give a hint to the presence of alanine-amino-peptidase (EC 3.4.11.2.) PMID- 8368032 TI - [Development of a magnetic urethral closure device--an animal experiment study]. AB - The new magnetic closure device consists of a retropubically implanted magnet and another removable intravaginal magnet, which gently closes the urethra. This system has shown its proper function in Merino sheep during a period of observation up to 33 weeks. The pressure on the tissue can be adjusted by the size and strength of the removable magnet. By using smooth-edged magnets, no necrosis of the vaginal wall and urethra could be observed. PMID- 8368033 TI - [The psychological status of the female with urinary incontinence]. AB - In the former western part of Germany, in 1989 about three million people claimed social costs because of urinary incontinence. 80 percent of them were women. The psychic situation of these women is mainly determined by social consequences of their incontinence. Behavioural changes to avoid incontinence lead to social isolation. A coherence between incontinence or urgency and agony or depression is acknowledged. Especially in elderly people, who have to change their well-known environment due to nursing problems, incontinence is a major problem, which often deteriorates with the new situation. Incontinence also leads to avoidance of sexuality. Women are mostly more irritated than their partners. On the other hand incontinence is used to avoid sexuality and thus may be a sign of a sexual conflict. PMID- 8368034 TI - [Fetal cyclopia with deletion 46,XX,del (7) (q32-->qter), prenatal diagnosis and genetic counseling]. AB - A pregnancy at 19./20. weeks of gestation with signs of cyclopia by ultrasonography is described. A long arm deletion of chromosome 7 was found by prenatal cytogenetic investigation. Prenatal diagnosis and genetic counseling are discussed. PMID- 8368035 TI - [Our gynecologic heritage. The activities of scientific gynecologic societies in Northeast Germany after the World War II]. AB - During the Second World War and especially since 1943 the activities of medical societies decreased more and more. The first gynecological meeting in the of Soviets occupied part of Germany happened October 5th till 6th 1946 in Jena. The Chairman was Gustav Doderlein. In May 1947 the Soviet Military Administration commanded the order Nr. 124 about foundation of medical societies. The Society of Gynecology at the University of Rostock was founded November 1947. In year 1948 was the unification with the Gynecological Society of Greifswald. The unified society organized till 1989 more than 40 meetings in the Northern towns of East Germany. 1991 the unification with the Northwestern Society of Gynecology and Obstetrics took place. The Society has now the name "North-German Society of Obstetrics and Gynecology". PMID- 8368036 TI - [Radicular paralysis with reference to lumbar root compression syndromes. Incidence, extent and follow-up in a neurosurgical patient sample]. AB - This is a retrospective study of 170 patients which were operated on for lumbar intervertebral disc herniation. The mean follow-up was 8 weeks. All patients showed muscular weakness before operation. Incidence, severity, and natural history of motor deficit following lumbar discectomy are reported. Moreover it was of special interest to analyze the effect of sex, age, severity and duration of muscular weakness, and timing of surgery on changes in radicular function. PMID- 8368037 TI - [Incidence of biopsy-detectable amyloid deposits in the retinaculum flexorum and in the tenosynovial tissue in carpal tunnel syndrome]. AB - Histological examination of surgical specimens from 98 patients with carpal tunnel syndrome revealed amyloid deposits in 12% of the cases. Amyloid was located in the flexor retinaculum and to the same extent in the tenosynovium. Serial sections of the material containing amyloid deposits demonstrated that examination of only one level would detect solely 90% of the amyloid-positive cases. In one single case amyloid deposits were considered extensive enough to cause compression of the median nerve and thus could have played a role in the pathogenesis of the carpal tunnel syndrome. In 8 of the 12 cases the patients' histories proved no correlation to preexisting diseases. In our opinion, an individual disposition may promote amyloid deposits as a response to local and chronic irritation. It is noteworthy that the mean age in the amyloid-positive group (70 years) is significantly higher than in the amyloid-negative cases (55 years). PMID- 8368038 TI - [Sacral anterior root stimulation to promote micturition in transverse spinal cord lesions]. PMID- 8368039 TI - The recurrent carpal tunnel syndrome. AB - Sixteen out of 720 patients with carpal tunnel syndrome who had undergone surgery since 1979 were reoperated for a "recurrence" (2.2%). Twelve of these patients had been originally operated on in our department. Thus, our own recurrence rate is 1.7%. Three patients deteriorated following surgery, 6 had an unsatisfactory improvement, and in 7 the symptoms recurred after initial improvement. Eight of the reoperated patients had a predisposing disease (terminal renal insufficiency, insulin-dependent diabetes mellitus, acromegaly). In 10 of the 16 cases the initial operation had been carried out by surgeons in the first three years of training. Reoperation revealed incomplete splitting of the transverse carpal ligament in 10 cases, compression of the median nerve by the scar in 4, injury of the muscular branch in 1, and an anatomical variant as cause of incomplete decompression in 1 patient. "Recurrences" after carpal tunnel surgery are predominantly due to inadequacies of the first procedure. A remarkable number of patients (50%) has predisposing diseases. Interfascicular or epineural neurolysis and complete exposure and neurolysis of the median nerve and its branches is necessary only in cases of recurrence. Their omission at the first surgery does not result in an increased recurrence rate. Our observations indicate that the number of operations for recurrent carpal tunnel syndrome can probably be reduced when the first operation is performed with care and experience. Patients with carpal tunnel syndrome secondary to a systemic disease are particularly at risk. PMID- 8368040 TI - [An innovative surgical glove: Manex extra strong--added safety in all operations]. PMID- 8368041 TI - Mucosal lesions of the digestive tract in cirrhosis. AB - Mucosal lesions of the digestive tract in cases of cirrhosis are described. The lesions include congestive gastropathy, antral vascular ectasia, erosions, brown macules and angiodysplasia in the stomach. Lesions are also observed in the duodenum and in the colon. PMID- 8368042 TI - Endoscopic varix ligation: a promising new technique? AB - Endoscopic varix ligation is a new promising endoscopic method which compete with endoscopic sclerotherapy both during acute bleeding and the chronic setting where the aim is to obliterate varices as soon as possible with minimal side effects. PMID- 8368043 TI - Photodynamic therapy and cancer of the esophagus. AB - Esophageal cancer is a tumor that, at diagnosis, is often advanced and not curable. In patients with good operative risk, surgery is still considered the ideal treatment. As many patients are elderly and have complicating serious medical conditions which preclude major resective surgery, endoscopic treatment (endoscopic oncology) has become a recent alternative. The endoscopic approach includes dilation, thermal destruction with Bicap probes, Nd. Yag laser, injection therapy, photodynamic therapy (PDT) and prostheses. This work is focused on photodynamic therapy which is safe but continues to be an experimental treatment. Its role in gastrointestinal malignancies is evolving. Currently the best results are to be expected in early lesions where the treatment could be curative. PMID- 8368045 TI - Endoscopic diagnosis and treatment of malignant biliary strictures: review of 505 patients. AB - The role of ERCP and endoscopic drainage in the diagnosis and treatment of patients with malignant biliary obstruction is well established. Endoscopic drainage is an effective therapy for palliation of malignant obstructive jaundice and does not preclude definitive treatment in appropriate candidate. We report our experience, in a retrospective review, of 505 patients with malignant biliary obstruction. In this series, endoscopic biliary drainage is shown to be safe and effective management for these patients. Relief of obstruction was obtained in a large majority of patients with a low, procedure related, morbidity and mortality. We conclude that ERCP, to diagnose and localize obstructive lesions, followed by endoscopic biliary drainage can be strongly considered in all patients with suspected malignant obstructive jaundice. PMID- 8368044 TI - Endoscopic management of chronic pancreatitis. AB - The indications of endoscopic management for chronic pancreatitis are strictly related to the classification of severe types and to the particular anatomy of the ducts: 1. Impacted or distal calculi: endoscopic pancreatic sphincterotomy (EPS) alone followed by ESWL when extraction fails. 2. Stone(s) and stricture: EPS, ESWL, NPC, and then 10F plastic stenting. 3. Relapsing strictures (with upwards dilatation) after 6 to 12 months stenting: silicone covered self expanding stent in a trial, versus surgical pancreaticojejunostomy. 4. Paraduodenal cyst bulging into the duodenum: ECD. 5. Jaundice and/or cholestasis due to stricture of the intrapancreatic CBD: 10F single or multiple plastic stent for calibration during 3 months. For relapsing cholestasis and stricture, 30F metal mesh stent versus surgical hepaticojejunostomy. The indications of endoscopic management for chronic pancreatitis are specific and require complete imaging and functional check up (ERCP, CT scanner, endosonography, pancreatic function tests). The technique is quite difficult and requires definition fluoroscopy, appropriate devices and experienced team. On this condition, the complication rate is very low and usually medically controlled. Treatment does not compromise any further surgery. Endoscopy allows to avoid or to postpone surgery which indication will become better defined and selected in the future. PMID- 8368046 TI - Endoscopic lithotripsy for bile duct stones. AB - Endoscopic sphincterotomy and common duct stone extraction is successful in 85 90% of patients using conventional balloons and baskets. However, most patients with biliary stones > 2 cm will require mechanical, electrohydraulic, or laser lithotripsy prior to stone extraction. Mechanical lithotripsy is inexpensive, easy to perform, and effective in 80-90% of cases. Most failures result from inability to entrap the stone in the lithotripsy basket. These cases may be successfully treated using either electrohydraulic or laser lithotripsy (intraductal shockwave lithotripsy). In most cases, intraductal shockwave lithotripsy requires direct visual control. Due to difficulty with peroral cholangioscopy, these techniques will not be widely used until a smaller, more maneuverable "mother and baby scope" system is developed. We recommend mechanical lithotripsy as the initial treatment for large biliary stones. Failed cases should be referred to specialized centers for a repeat attempt with intraductal shockwave lithotripsy. With this approach, an experienced endoscopist is successful in removing biliary stones in over 95% of patients. Long term biliary stenting remains a viable option for the high risk patients with large common bile duct stones. PMID- 8368048 TI - [Value of interferon-alpha in treatment of chronic myeloid leukemia]. AB - In 1983 Talpaz et al. (43) for the first time demonstrated the efficacy of interferon-alpha (IFN-alpha) for the treatment of patients with chronic myelogenous leukemia (CML). This observation has been confirmed by several study groups in the consecutive years. An overview over the 7 largest trials including more than 400 patients reveals response rates (partial and complete hematological remissions) of 55 to 91%. In contrast to conventional chemotherapy IFN-alpha treatment resulted in a decrease of Philadelphia-chromosome positive metaphases (cytogenetic remissions) in 19 to 47% of these patients. A complete disappearance of the Philadelphia chromosome was found in 5 to 10% of patients. The following factors influence the response to IFN-alpha in patients with CML: phase and duration of the disease, several well defined risk factors, and IFN-dose. Currently available data are strongly suggestive for a survival benefit of patients with cytogenetic remissions, although definitive prove by phase-III trials is lacking. Actual studies focus on combinations of IFN-alpha and cytostatics, e.g. low-dose cytosine arabinoside. PMID- 8368047 TI - Biochemical and histopathological aspects in duodenogastric reflux gastritis patients with or without prior cholecystectomy. AB - The aim of this study was to evaluate some biochemical and histopathological aspects in a group of patients with a view to identifying any differences depending on whether the pathology was associated with previous cholecystectomy or idiopathic. The study involved 23 patients (8 post-cholecystectomy cases and 15 ulcer-free dyspeptic patients) with the diagnosis of duodenogastric reflux gastritis confirmed by endoscopic histopathological evaluation. The following parameters were considered: 1. pH and bile salt concentration in gastric juice; 2. histological classification of antral biopsies (Niemela's criteria); 3. dyspeptic symptoms (dyspepsia, pyrosis and epigastric pain, sense of repletion, foul-tasting mouth) graded on a scale from 0 to 4. All parameters were considered in relation to whether or not Helicobacter Pylori was found in the histological specimens. No significant differences were found between the two groups for pH and bile salt values or for Helicobacter Pylori positivity. No relationship was observed between the Helicobacter Pylori and either the severity of the histological picture, the features of the biochemical parameters or the severity of the clinical symptoms. Such findings confirm the common pathophysiological pattern of reflux gastritis regardless of any permanent biliary tract alterations and the low importance of Helicobacter Pylori infection in determining this syndrome. PMID- 8368049 TI - [Highly malignant non-Hodgkin's lymphomas]. AB - High malignant non-Hodgkin's lymphomas are rare diseases, with a rising incidence. A qualified histological classification and a thorough staging are the most important points in the further management. The treatment is primarily chemotherapeutic; radiation is only used in selected situations. The success of the very first therapy is most important for the outcome. To date no one of the modern intensive treatment regimens could show an advantage over conventional CHOP. For treatment failures autologous or allogenic bone-marrow-transplantation is the best option. Whether bone-marrow-transplantation in first remission can improve the treatment results waits to be answered. HIV-associated lymphomas are an increasing problem. For selected patients intensive chemotherapy with growth factors seems to improve the results. Conflicting are the therapy data in elderly patients. Most centers accept a higher lymphoma mortality with reduced doses. With special designed treatment regimens it is probably possible to come to an acceptable outcome even in elderly patients. PMID- 8368050 TI - [Successful intubation with the Combitube of two patients with bull neck]. AB - Endotracheal intubation is without doubt the optimal method for emergency airway management. Rapid intubation and effective ventilation are the major aims during cardiopulmonary resuscitation. As an alternative, the Combitube can be used whenever endotracheal intubation is not immediately possible. We report the successful use of the Combitube during cardiopulmonary resuscitation in two patients with bull-neck. The patients could be oxygenated and ventilated adequately with the Combitube. This case report shows that the Combitube may be a valuable tool for emergency intubation in difficult situations. PMID- 8368051 TI - Managed care: its impact upon CRNA practice. PMID- 8368052 TI - Mivacurium: a replacement for succinylcholine? PMID- 8368053 TI - Accreditation of regionalized and comprehensive nurse anesthesia programs. AB - Regionalized educational systems are becoming more common among nurse anesthesia programs and represented 41 out of 86 programs in a 1992 survey. Surveys were mailed to program directors of all nurse anesthesia programs accredited by the Council on Accreditation of Nurse Anesthesia Educational Programs to determine if the directors perceived a need for three separate categories of accreditation. Responses indicated that, although most directors saw no benefit in applying for separate academic and clinical accreditations for their own programs, they did believe the additional accreditation options should be available to all programs. Most directors also indicated that they preferred the Council to continue offering only one category of accreditation while 33 (38%) indicated they were interested in separate accreditation categories. PMID- 8368054 TI - Captain of the ship. PMID- 8368055 TI - Writing the grant proposal. AB - This article provides AANA members who are interested in seeking external funding with information that will assist them in writing a grant application. Avenues of initial contact with the funding agency are discussed, as are suggestions for drafting the appointment letter and the letter of inquiry. The development of a narrative for a grant application depends on the guidelines set forth by the funding agency and varies from agency to agency. A list of information that might be included in a narrative is provided. PMID- 8368056 TI - Anesthesia quality plus: the quantification of competence. PMID- 8368057 TI - An anesthesia quality improvement program utilizing a computer database to effect change. AB - This article describes the perceived benefits of a quality improvement program, briefly discusses the steps involved in the establishment of such a program, and describes the implementation of a computer database for data collection and retrieval. The outcome of 4,500 anesthesia cases, representing 30 months of casework, is included. This article concludes with a discussion of the strengths and weaknesses of the program as well as a suggestion for future quality improvement endeavors. PMID- 8368058 TI - The attrition rate of students in master's level nurse anesthesia programs. AB - This survey was conducted in October 1990. Survey forms were sent to all nurse anesthesia programs offering master's degrees. The purpose of the study was to determine the dropout rate of students who did not complete their programs during the period from 1985 to 1990. Directors were asked to rate their satisfaction to determine if students were more likely to leave because of clinical or academic difficulties or for personal reasons. The time frame and the circumstances surrounding the students' departures were also examined. The attrition rate of programs ranged from 0-25% (mean = 8.2%). More than half the students left for personal reasons. The remainder were almost equally divided between clinical and academic reasons. In fact, many directors had difficulty distinguishing between these two causes. Most students left during the first 12 months of their program, and more than half of them were not encouraged to resign. A large majority (78%) of directors found their program's attrition rate to be very acceptable. PMID- 8368059 TI - AANA journal course: update for nurse anesthetists--beyond the laryngoscope: advanced techniques for difficult airway management. AB - Airway catastrophes have been identified as the leading cause of injury and death during anesthesia. Proper management of a patient with a technically difficult airway commences with problem recognition. Physical limitations to mask ventilation and endotracheal intubation may be accurately identified by thorough observation. All patients should be examined for oral structure visibility, size of mandibular space, and ability to assume "sniffing" position. Patients with compromised airways should have patency secured while remaining awake by direct laryngoscopy, nasotracheal intubation, fiberoptic endoscopy, retrograde intubation, or possibly tracheostomy. Partial or complete airway obstruction requires immediate recognition and intervention. Repeated, unsuccessful attempts at endotracheal intubation should be avoided, as these may lead to laryngeal edema or hemorrhage which may critically compromise airway maintenance. Prudent options may include awakening the patient, proceeding with mask ventilation, or performing semi-elective tracheostomy. Emergency airway access may be achieved with a tracheoesophageal airway, esophageal tracheal combitube, laryngeal mask airway, digital intubation, or obtained surgically by transtracheal jet ventilation or tracheostomy. Reduction of airway-related morbidity and mortality is best achieved with an understanding of airway anatomy, common causes and prompt recognition of compromise, and alternative techniques of establishing patency and ventilation. PMID- 8368060 TI - HCFA issues 1993 CRNA Medicare conversion factors. PMID- 8368061 TI - Epidural and intrathecal analgesia in a rural setting. AB - Epidural anesthesia--alone or in combination with general anesthetic agents--is beneficial to physiological and cardiovascular stability during surgery. The placement of an epidural catheter at the time of surgery also provides access for the administration of epidural narcotics for postoperative analgesia. This article describes how a rural acute care facility initiated a program of epidural analgesia administered by the nursing staff under the direction of the anesthesia department utilizing AANA protocol.* In such a setting, an educated nursing staff can serve as an extension of the anesthetist in overseeing patient response to epidural and intrathecal narcotics. PMID- 8368062 TI - A case report: the use of ketamine and midazolam intravenous sedation for a child undergoing radiotherapy. AB - The combination of ketamine hydrochloride and midazolam was used to successfully provide intravenous sedation for a child requiring daily radiation treatments. During the radiation therapy treatments, the anesthesia provider was not in direct contact with the patient. Traditional monitoring was complemented by the addition of closed-circuit television monitoring. The drug combination provided consistent cardiac and respiratory stability, as well as patient immobility, for each radiation treatment. PMID- 8368063 TI - Bacteremia in children with acute lymphoblastic leukemia. AB - Bacteremia is one of the important complications of the treatment of hematological malignancy. In this report, we analyze bacteremias in 72 children with acute lymphoblastic leukemia who were admitted to our hospital from July 1, 1988 to October 31, 1991. Positive blood cultures were found in 26% (19/72) of the patients. There were 24 episodes of bacteremia; Gram-negative, Gram-positive and mixed bacteremia comprised 62.5% (15/24), 33.3% (8/24) and 4.2% (1/24), respectively. E. coli, klebsiella pneumoniae and Pseudomonas aeruginosa were the three most common pathogens. Eighty-three percent of the bacteremic episodes occurred during neutropenia (absolute neutrophil count below 500/mm3). Our data suggest that a Pseudomonas etiology, associated pneumonia, and shock accounted for a poor outcome. The over-all mortality for bacteremic events was 26.3% (5/19). Intensive supportive treatment and effective antibiotics are the most important factors in improving the outcome of bacteremia. The success in recent ALL treatment can be attributed in part to the improved outcome of bacteremia. PMID- 8368064 TI - Risk factors of coronary arterial aneurysm in Kawasaki disease. AB - From April 1983 to August 1991, 70 cases of Kawasaki disease were admitted to Taiwan Provincial Tao-Yuan General Hospital. Fifty-seven patients treated with aspirin 80-100 mg/kg/day alone during the acute phase were followed by two dimensional echocardiography for two weeks to two years. Twelve cases (21%) complicated with coronary arterial aneurysm (CAA) were referred as high risk group. Those who had no CAA were a low risk group. Stepwise discriminant analysis was performed to obtain risk factors of CAA based on clinical and early laboratory data. This yielded a classification accuracy of 75.4%. The combination of two parameters, white blood cell count and C-reactive protein, can be applied to early identify Kawasaki patients at high or low risk of CAA. PMID- 8368065 TI - [Heavy metals in traditional Chinese medicine: ba-pao-neu-hwang-san]. AB - Heavy metal intoxication of newborn infants fed with "Ba-Pao-Neu-Hwang-San" has been reported every year by many hospitals in Taiwan. About nine years ago, the National Laboratories of Foods and Drugs of the Department of Health, Executive Yuan, received one case report of a five month old female infant who died as a result of long term feeding with "Ba-Pao-Neu-Hwang-San". The drug was found to have contained lead 44,000 ppm. Although this unfortunate incident was propagated by most newspapers, the prescription of this ancient Chinese medicinal preparation is still widely accepted by ordinary people. Herbal medicine doctors prefer complex mineral drugs as did their ancestors thousands of years ago. In the last two years, we have collected 5 samples of "Ba-Pao-Neu-Hwang-San" from different manufacturers and measured the concentration of 16 heavy metals (including Cadmium, Mercury, Arsenic, Lead, Chromium, Manganese, Selenium, Germanium, Nickel, Calcium, Magnesium, Aluminum, Iron, Copper, Zinc, and Vanadium) in these drugs with Inductively-Coupled Plasma Atomic Emission Spectrometry and Graphite Furnace Atomic Absorption Spectrometry. The result of our survey revealed that the first sample (from Tainan) contained mercury 52,800 ppm, the fourth (from Ping-tung) contained mercury 34,500 ppm, and the fifth (from Sin-chu) contained mercury 65,700 ppm. The mercurial contents of these samples were apparently too high to be a safe drug. PMID- 8368066 TI - Congenital syphilis: report of twelve cases. AB - Between 1983 and 1992 at the Taichung Veterans General Hospital, twelve congenital syphilis patients were diagnosed, according to the Centers for Disease Control (CDC) criteria. For the five boys and seven girls, ages at diagnosis ranged from 1 day to 8 months, with an average of 23 days. Among these 12 patients, four (33%) were premature. Seven patients (58%) were diagnosed in the past three years. These 12 patients were divided into inborn and outborn patient groups. Serological tests for syphilis were done in all inborn patients, but none in the outborns. All five outborn patients were symptomatic. In comparison, only one of seven inborn infants showed clinical evidence of congenital syphilis. The mean age at diagnosis was obviously older in the outborn patient group (53 days vs. 1 day). Six of ten patients (60%) had cerebrospinal fluid (CSF) abnormalities, while four of nine (44%) showed radiological abnormalities of bones. The hematologic and biochemical abnormalities compatible with congenital syphilis were also described. Penicillin was the drug of choice in ten patients. Despite adequate treatment, one patient died of respiratory failure. There has been no evidence of any signs of late congenital syphilis in those patients who survive. Congenital syphilis, a serious but preventable disease, is best treated adequately and early for minimal sequelae. PMID- 8368068 TI - Persistent truncus arteriosus associated with interrupted aortic arch: report of two cases. AB - Two neonates with a combination of truncus arteriosus and interruption of the aortic arch, so-called type A4 of the Van Praagh classification, are reported. Both presented as tachypnea, poor appetite and increasing cyanosis during the first week of life. The combination of these defects significantly increases the surgical risk. Di-George syndrome was noted in one patient, who presented with hypocalcemia and T cell dysfunction. Autopsy confirmed this diagnosis. PMID- 8368067 TI - Rhabdomyolysis syndrome in children: report of three cases. AB - Three cases with distinct clinical manifestations associated with rhabdomyolysis syndrome were encountered in this hospital's pediatric intensive care unit. Elevation of serum creatine phosphokinase, uric acid, potassium, inorganic phosphate and hypocalcemia with seizure were noted. The three patients all had signs of acute renal failure. One died of respiratory failure, and autopsy revealed multiple intrathoracic anomalies. The remaining two recovered completely from rhabdomyolysis. It is of importance to early recognize any acutely ill patient as having rhabdomyolysis syndrome when there is elevation of muscle enzymes, hypocalcemic seizure, positive orthotolidine reaction of urine strip while negative finding of red blood cell. The syndrome may damage the kidneys. Appropriate management to induce diuresis usually can salvage this potentially life-threatening condition. PMID- 8368069 TI - Congenital chylothorax managed by partial pleurodesis: report of one case. AB - Congenital chylothorax, a rare cause of respiratory distress in neonate, presented here with respiratory distress from two days of age. Thoracocentesis was performed at six days, revealing a clear fluid with high protein content. Thoracotomy was performed at the age of 33 days because of a profuse amount of chest tube drainage. A leak of chyle was found near the esophageal hiatus of the costophrenic angle. Partial pleurodesis was performed because of difficulty in identifying the exact leakage point. Respiratory status improved very quickly after the operation, and oral intake was well-tolerated during follow-up. PMID- 8368070 TI - Rigid spine syndrome presenting with respiratory failure--report of one case. AB - A case of rigid spine syndrome presenting with respiratory failure was reported. A seven-year-old girl had had dyspnea and orthopnea for one month. Symptoms had aggravated gradually and she was in a state of respiratory failure on arrival at our hospital. There was no evidence of active lung lesions and response to mechanical ventilation was good. Physical examination revealed an extremely thin girl with marked flexion limitation of neck and severe wasting of sternocleidomastoid and intercostal muscles. Serum creatine phosphokinase was moderately elevated (801 IU/L). Muscle biopsy specimen obtained from the right quadriceps femoris revealed increased perimyseal connective tissue and marked Type II fiber atrophy. Electromyography of left paraspinal muscles demonstrated small amplitude, short duration motor unit potentials. She received tracheostomy and a home-care ventilator use during sleep. Ventilatory insufficiency, though rare, should be anticipated in patients with rigid spine syndrome, and timely ventilatory support should be given. PMID- 8368071 TI - [Bronchopleural fistula in a newborn: report of one case]. AB - Persistent pneumothorax is infrequently seen in the neonate. Persistent pneumothorax with a large air leak and empyema may indicate the presence of a bronchopleural fistula which often results in mortality in infants requiring ventilator support. A ten-day-old female neonate with meconium aspiration syndrome was found to have respiratory distress after birth. During ventilator therapy, persistent pneumothorax with a large air leak from the chest tube was found. Empyema occurred three days later. Despite insertion of multiple chest tubes and use of bronchial balloon occlusion, a large air leak and empyema still were noted. Following thoracotomy and suture of the bronchopleural fistula, the air leak stopped. The patient was smoothly weaned from the ventilator. She was able to be discharged in good condition six weeks later. In management of the bronchopleural fistula, bronchial balloon occlusion enabled the patient to be maintained until more specific therapy could be attempted. Thoracotomy is definite therapy for selected infants requiring ventilator support who demonstrate a large air leak, persistent pneumothorax, and progressive hypoxia which is unresponsive to chest tube insertion. PMID- 8368073 TI - [Scavenging effects of cyproheptadine on oxygen free radicals]. AB - The scavenging effects of cyprohepdadine (Cyp), an antiserotonin-antihistaminic agent with significant calcium channel blocker activity, on oxygen free radicals were studied. Cyp was found to significantly scavenge the hydroxyl radical (.OH) produced by Fenton reaction (Fe(2+)+H2O2) (EC50 = 54 mumol/L) and inhibit the rate of .OH generation (IC50 = 22 mumol/L). The inhibitory effects of Cyp were significantly more potent than those of mannitol, a specific .OH scavenger, with EC50 of 22.7 mmol/L and 10.7 mmol/L respectively. Cyp was also shown to have certain scavenging effect on superoxide anion (O2-.) produced by peritoneal polymorphonuclear leukocytes (PMNs) in rats (IC50 = 179 mumol/L). These results suggest that the anti-myocardial injury activity of Cyp may be, at least partially, related to its scavenging effects on oxygen free radicals. PMID- 8368072 TI - [Absent pulmonary valve syndrome in tetralogy of Fallot: report of two cases]. AB - A combination of absence of the pulmonary valve with ventricular septal defect, annular pulmonary stenosis and aneurysm of the pulmonary artery is called "absent pulmonary valve syndrome". Most patients with this condition suffered from severe respiratory symptoms in early infancy. Respiratory failure which is the leading cause of mortality in infants with this syndrome, results from pulmonary emphysema, pulmonary atelectasis or pulmonary infection as a consequence of compression of the bronchus by the pulmonary aneurysm. If these patients can be treated medically to survive beyond one year old, gradual decrease in severity of symptoms is expected. A definite correction in childhood is recommended. Otherwise, palliative operation in infancy has a high mortality rate. This paper reported two cases with severe symptoms in infancy; one patient expired at nine months of age, and the other lived beyond one year to receive surgical correction at the age of three. The etiology, clinical features and treatment of absent pulmonary valve syndrome are also discussed. PMID- 8368075 TI - [Antagonistic effects of cholinergic drugs on xylazine induced sedation]. AB - Xylazine induced sedation in mice was observed as a kind of inhibition of exploratory activity. The reversible cholinesterase inhibitor cui xing ning (0.25 1.0 m.kg-1), the precursor of acetylcholine, choline bromide (100-300 mg.kg-1), and the M-receptor agonist arecoline (1.0-5.0 mg.kg-1) were shown to significantly antagonize xylazine (5.0 mg.kg-1) induced sedation. While cui xing ning (0.25 mg.kg-1) shifted the dose-response curve of xylazine induced sedation to the right, hemicholinum-3 (3 micrograms icv), which inhibits the synthesis of acetylcholine, shifted the dose-response curve to the left. These results suggest that the xylazine induced sedation may be partly due to a reduced central cholinergic function. Cui xing ning may have some value in the treatment of xylazine overdose and antagonize the anesthesia induced by anesthetics combined with xylazine. PMID- 8368074 TI - [The permissive action of glucocorticoid on the analgesic effect of kyotorphin and its analogue]. AB - Kyotorphin (KTP) is an endogenous analgesic dipeptide which does not act on opiate receptors but may induce the release of endogenous opioid met-enkephalin. In order to investigate whether or not glucocorticoids have "permissive action" on KTP, hydrocortisone has been used to examine its action on the analgesic activities of KTP and its retro-isomer (riKTP) by employing thermal irradiation tail flick method after intracerebroventricular injection. KTP and riKTP showed dose-dependent analgesic activity. Dose of KTP in the range of 6-24 mmol/L were effective, while the dose of riKTP at 6 mmol/L was shown to be ineffective. The analgesia of KTP was higher than that of riKTP. Hydrocortisone alone showed no significant analgesic effect. Linkers by connecting hydrocortisone with KTP or riKTP showed significantly higher analgesic effect compared with the corresponding dipeptides, not only in the duration of analgesia but also in potency. Solutions containing hydrocortisone and any one of the dipeptides exhibited the same effect as the linker. Pretreatment with sc naloxone (10 mg/kg) 15 min before icv of KTP or riKTP (24 mmol/L) could not block the analgesia. These findings implicate that: (1) Glucocorticoids have a permissive action on the analgesia of KTP and its retro-isomer. The glucocorticoids may exert its effects by acting on receptors in the membrane, and thus cause fast membrane effect. (2) KTP may also induce release of substances other than met-enkephalin to participate in the analgesia. PMID- 8368076 TI - [Pharmacokinetics of muscone in rats, rabbits and dogs]. AB - The plasma concentration--time course of muscone in rats after a single i.v. administration fitted well to a two-compartment open model, and those in rabbits and dogs were all conformed to a three- compartment open model. Significant species differences were observed in the pharmacokinetic parameters among rats, rabbits and dogs, while no significant differences were found among the three dosages of 12, 18 and 24 mg/kg after i.v. administration to rats. In rats, the T1/2 beta was found to be 118.1-131.2 min. In rabbits and dogs, the T1/2 beta were 24.9 and 30.0 min, respectively and the T1/2 gamma were 331.9 and 366.4 min, respectively. In rats, rabbits and dogs, the Vss were 23.0, 51.7 and 7.3 L/kg, respectively, and the Vc were 2.33, 2.13 and 0.38 L/kg, respectively. PMID- 8368077 TI - [Diterpenoid alkaloids from Aconitum gymnandrum]. AB - Aconitum gymnandrum maxim. (ranunculaceae) is used as an herbal medicine in Tibet area. A new diterpenoid alkaloid, gymnandine (I) along with known alkaloids 14 acetyl-8-O-methyltalatisamine (II), acoforine (III), columbidine (IV), aconitine (V), ranaconitine (VI), talatizidine (VII), isotalatizidine (VIII), gymnanconitine (IX), talatisamine (X), and atisine HCI (XI) have been isolated from this unique species. The structure of I is determined on the basis of spectral evidences and comparison of the 13CNMR spectrum with that of denudatine. II has not been previously reported as a natural product and III-VII were isolated from this plant for the first time. PMID- 8368078 TI - [Isolation and identification of yibeinoside B]. AB - A new C-nor-D-homosteroidal alkaloid named Yibeinoside B was isolated from the bulb of Fritillaria pallidiflora Schrenk by column chromatographic techniques. The structure has been determined based on spectral and chemical data. PMID- 8368079 TI - [Studies on the chemical constituents of Desmodium styracifolium (Osbeck) Merr]. AB - A new alkaloid, named desmodimine, C12H15NO4, gum, and a new natural product, named desmodilactone, C8H13NO3, mp 84-85 degrees C have been isolated from the aerial parts of Desmodium styracifolium (Osbeck) Merr. belonging Leguminosae. On the basis of spectral analysis their structures were deduced as formula I and II. In addition, lupenone (III), lupeol (IV), tritriacontane (V), stearic acid (VI), eicosanoic acid eicosyl ester (VIII) and beta-sitosterol (VII) were isolated for the first time from this plant. PMID- 8368080 TI - [Studies on the chemical constituents of Croomia japonica Miq]. AB - A new steroid alkaloid, namely croomionidine (II), together with four known compounds pachysamine A(I), croomine (III), didehydrocroomine (IV) and beta sitosterol were isolated from the roots of Croomia japonica Miq. Their structures were identified by IR, MS, 1H NMR, 13C NMR and chemical conversion. PMID- 8368081 TI - [Studies on PAF antagonistic bicyclo(3,2,1) octanoid neolignans from Piper kadsura]. AB - As a continuation of our previous report dealing with the structures of novel neolignans from Piper kadsura (Choisy) Ohwi, two other new bicyclo(3,2,1) octanoid neolignans, named kadsurenin K and kadsurenin L, were isolated. On the basis of spectral analysis and chemical derivatization, their structures were established as 7R,8R,3'R,5'R-delta 8'-3,5'-dimethoxy-4-hydroxy-2',3',4',5' tetrahydro-2', 4'-oxo-7.3',8.5'-neolignan and 7R, 8R, 3'S, 4'R, 5'R-delta 8' 3,4,5'- trimethoxy-4'-acetoxy-2',3',4',5'-tetrahydro-2'-oxo-7.3', 8.5'-neolignan respectively. Kadsurenin B and kadsurenin C were known compounds. In 3H-PAF receptor binding assay, kadsurenin B, C, K and L demonstrated significant PAF antagonistic activity. PMID- 8368082 TI - [The structure identification of zhepiresionol]. AB - A new 3,7-dioxabicyclo[3, 3, O] octan-6-one named zhepeiresinol was isolated from Fritillaria thumbergii Miq. The spectroscopic and X-ray diffraction analysis established the structure as 2-(3',5'-dimethoxy-4'-hjydroxyphenyl)-3,7 dioxabicyclo[3, 3, O]octan-6-one. PMID- 8368083 TI - [Determination of cefixime in human plasma and urine using high performance liquid chromatography column switching technique]. AB - A double column and double pump HPLC switching system is described for the analysis of cefixime in human plasma and urine. The system used muBondapak C18 short pretreatment column for on-line sample clean-up and a Hitachi GEL 3056 (ODS) analytical column for separation. A mixed solution of 0.01 mol/L H3PO4-0.1 mol/L KH2PO4-H2O (20:1:79) was used as the pretreatment mobile phase and CH2CH 0.01 mol/L H3PO4-0.1 mol/L KH2PO4-H2O (13:20:1:66) was used as analytical mobile phase. The compound in plasma and urine is detected by ultraviolet absorption at 286 nm and 314 nm, respectively. The absolute recoveries of the method in plasma and urine were 99.1% and 98.6% respectively. The relative standard deviations of the method are 0.70-3.82% and 0.80-3.73% in plasma, 1.53-3.08% and 1.31-2.67% in urine between days and day-to-day. Linear calibration curve for cefixime was measured over the range of 0.1-3.2 micrograms/ml in plasma and 1.0-32.0 micrograms/ml in urine, and the correlation coefficients were all 0.9999. The detection limit was 0.05 micrograms/ml in plasma and 0.2 micrograms/ml in urine. The plasma and urine samples were diluted with water and injected directly onto the HPLC system. The operation is simple and the relative sensitivity is markedly increased because of higher recoveries and larger loading capacity of the sample. PMID- 8368084 TI - [Studies on electrochemical behaviour of antiepilepsirine and its adsorptive voltammetry]. AB - Antiepilepsirine is a kind of new antiepileptic drug. In this paper, a new method, adsorptive voltammetry (ADV) has been established for the determination of antiepilepsirine. In 0.20 mol/L H2SO4 solution, a sensitive reduction wave of antiepilepsirine was obtained by ADV after preconcentration on the surface of hanging mercury drop electrode (HMDE) (Ei = 0.7V, v = 100 mV/s), the peak potential was -0.94V (vs Ag/AgCl). The linear range between the peak current and the concentration of antiepilepsirine was 3.0 x 10(-9)-3.0 x 10(-6) mol/L with a detection limit of 1.0 x 10(-9) mol/L. Antiepilepsirine in tablet and urine samples was determined by using this method. The electrochemical behaviour of the system and its electrode reaction mechanism were studied by means of linear sweep and cyclic voltammetry, constant potential coulometry, normal pulse polarography (NPP), etc. The diffusion coefficient D was 7.7 x 10(-6) cm2/s. The electrode reaction rate constant was 1.5 x 10(-3) cm/s. The number of reduction electron n was 2. The electron transfer coefficient was 0.52. The electrode reduction process was shown to be irreversible with the adsorptive characteristics. PMID- 8368085 TI - [Study of quality control on herbal drugs and preparations of daqingye and banlangen]. AB - This paper first suggests that 2,4 (1H,3H) quinazolinedione (QZL) may be used as a quality control standard for the Chinese herbal drugs Daqingye (Folium Strobilanthis et Polygoni) and Banlangen (Radix Strobilanthis) as well as its preparations. QZL was found for the first time from the above mentioned two Chinese herbal drugs which has a representative property. Its content is stable. This made it possible to solve the difficulty of quality control for the preparations "antipyretic and common cold granules" and "Banlangan granules" and provide a reliable assay method to evaluate the quality of the herbal preparations. By changing the wavelength and using gradient elution in HPLC, 3 constituents can be determined through one injection by the present method, thus the time of determination may be shortened and the efficiency of assay increased. The method showed good linearity (r = 0.99998, n = 4) in the range of 0.2-3.2 micrograms/ml of QZL, the average recovery was above 95% with RSD < 1.5% (n = 3). HPLC condition: Column: LiChrosorb RP 18; elution gradient: methanol from 35% to 90% in water solution; determination wavelength: 226 nm and 288 nm. PMID- 8368086 TI - [Synthesis of N-substituted polymethylene dicarboxamides as inducers of differentiation]. AB - N-Alkyl polymethylene dicarboxamides are known potent inducers of erythroid differentiation in murine erythroleukemia cells. The most active inducer N,N,N',N'-tetramethyl-1, 6-hexane-dicarboxamide has the same effectiveness as HMBA which has entered clinical trials as a differentiating agent. These compounds also have inducing activity in HL-60 human promyelocytic leukemia cells. In this paper, the synthesis of a series of N,N'-bis[2-(2-thiazolinyl)], N,N'-bis[5-(1-methyl-2-pyridonyl)], N,N'-bis[3-(1-phenyl-5-pyrazolonyl)] polymethylene dicarboxamides and 3,3'-(polymethylene dicarbonyl)bis(1-methyl-2 imidazolidine-thiones) is reported. The inducing activities of the compounds were evaluated in vitro with HL-60 human promyelocytic leukemia cell line. Among them, N,N'-bis[2-(2-thiazolinyl)]-1,8-octamethylene- dicarboxamide (I4) and N,N'-bis[5 (1-methyl-2-pyridonyl)]-1,6-hexamethylenedicarboxami de (II3) were shown to be relatively effective inducers of differentiation. PMID- 8368088 TI - [The plan. Change. Homage]. PMID- 8368087 TI - [Chemical studies of Strobilanthes cusia]. AB - Seven compounds have been isolated from the whole plant of Strobilanthes cusia (Nees) O. Ktze. Three of them are triterpenes (I-III), two are indole alkaloids (IV, V), two are quinazolinone alkaloids (VI, VII). On the basis of spectral analysis and physicochemical properties, their structures were established as lupeol (I), betulin (II), lupenone (III), indigo (IV), indirubin (V), 4(3H) quinazolinone (VI), 2,4(1H,3H)-quinazolinedione (VII). VI and VII were found from natural plant for the first time. The results of the pharmacological tests demonstrate that compound V has anticancer activity and compound VI has hypotensive action. Compound VII can be quantitatively determined by HPLC, which may serve as a quality control standard for materia medica and its preparations. Compounds VI and VII have been confirmed by means of synthesis. PMID- 8368090 TI - [Functional assessment of the autonomic nervous system in rheumatoid arthritis]. AB - Sympathetic and parasympathetic nervous system evaluation was performed in 21 patients with rheumatoid arthritis. Every patient had autonomic nervous system (ANS) dysfunction, the parasympathetic involvement being the most frequent. ANS dysfunction may explain some manifestations and may well be the expression of a larger neuropathic involvement with pathogenic implications. PMID- 8368089 TI - [Chronic hepatitis: the etiological spectrum. The implications for treatment]. AB - The prevalence of chronic hepatitis and its different aetiologies was studied in all patients above 10 years of age seen in the specialised outpatient clinic of our hospital over a 3 year period. Defining chronic hepatitis as a persistent elevation of the transaminases, 988 patients (62% of all the patients observed) were classified as follows: viral aetiology in 82%, metabolic in 2%, biliary in 2%, alcoholic in 11%, autoimmune in 1.5% and idiopathic in 2%. Among the viral group, hepatitis B virus infection was predominant (65%), followed by hepatitis C virus (26%) and delta hepatitis (8%). While the hepatitis C and delta patients presented high transaminases, in the HBsAg carriers this occurred in 94% and 20% of the HBeAg and anti-HBe-positive patients, respectively. Thirty per cent of the patients with chronic hepatitis B, 35% of those with chronic hepatitis C and 18% with delta hepatitis were selected for alpha interferon therapy. This demonstrated that in a significant proportion of patients with chronic viral hepatitis, therapy with interferon is not indicated. Corroborating other studies, with even stronger data, our study shows that viral aetiology is the most frequent type of chronic hepatitis. PMID- 8368091 TI - [Cervical discectomies by the anterior approach]. AB - A retrospective study was made of sixty patients who underwent anterior cervical surgery, between January, 1980 and May, 1989. The standard anterior approach devised by Cloward (DEC) was used for 28 patients, and discectomy alone (DS), without bone graft, for the other 32. The postoperative stay was 2.4 times longer after DEC than after DS. Surgical complications had an incidence of 11.6%, 14.3% with DEC and 9.3% with DS. There was no mortality. A total of 57 patients were available for transversal clinical evaluation, 26 of the DEC group and 31 of the DS group. There was no difference in the success rate between the two groups. Considering the over-all results, 77.2% had good or excellent results, 10.5% had fair results and 12.3% had poor results. Patients with radicular symptoms alone had better results. Evolution of the spine stability at the level of the intervention was of no major difference between the two groups. The authors conclude that there are identical results, whatever the technique used. Still, morbidity and postoperative hospitalization are higher with Cloward's approach, which seems a good reason to restrict its use to cervical instability situations, namely traumatic cervical pathology. PMID- 8368092 TI - [Neurophysiological methods for the diagnosis of genitourinary dysfunctions]. AB - Genito-urinary function is a watershed field interesting several areas of medical concern. Neurophysiological studies allow objective assessment of central, peripheral and autonomic pathways in the nervous system contributing to topographical localisation of lesions. The authors describe different methods used, namely somatosensory evoked potentials by pudendal nerve stimulation, bulbo cavernous reflex, cutaneous sympathetic reflex, transcranial cortical or spinal magnetic stimulation and single fiber EMG. Abnormalities in neurological diseases are presented. PMID- 8368093 TI - [Miller Guerra. Physician, professor, master]. PMID- 8368094 TI - [Echo Doppler in abdominal aortic dissection]. AB - The authors present a case of abdominal aorta dissection--type B. The diagnosis was made by Doppler ultrasound and computerized tomography (CT). The use of Doppler ultrasound in the diagnosis and assessment of abdominal aorta dissection and visceral arterial involvement is discussed. Doppler ultrasound is also a useful imaging technique in follow-up evaluation if conservative treatment is employed. PMID- 8368095 TI - [Emphysematous pyelonephritis]. AB - A case of emphysematous pyelonephritis to E. coli, in a 63-year-old female diabetic patient is presented herein. Imaging techniques (plain abdomen X-Ray, ultra-sonography and computed tomography) allowed the authors to make the diagnosis. Percutaneous nephrostomy, combined with medical therapeutics, contributed to a favourable clinical evolution of the patient. PMID- 8368096 TI - [Resistance to the action of insulin]. AB - The author analyses the insulin and glucagon effect on glycaemia regulation. The structure of glucose transporters and insulin receptors is described in some detail. Finally the author attempts to explain the insulin resistance mechanism based on a post receptor alteration that would be advantageous in traditional nutrition, but is noxious in a western type society, due to excessive caloric intake. PMID- 8368097 TI - [Combined therapy in non-insulin-dependent diabetes mellitus]. AB - In recent years an improved understanding of potential complications associated with hyperinsulinemia has led to a growing interest in alternatives to insulin monotherapy for patients with non-insulin-dependent diabetes mellitus, who have failed on a regimen of diet and sulphonylureas. These patients typically present normal or elevated levels of insulin. This problem which has been attributed to insulin resistance, is superimposed on the peripheral hyperinsulinemia resulting from subcutaneous insulin delivery. A plethora of clinical trials have reported on the efficacy of combining therapy in limiting insulin requirements while achieving better glycemic control. This paper attempts a critical review of the pros and cons with respect to combining therapy and provides guidelines for its practical use. PMID- 8368099 TI - [Critical analysis of the bibliography of Actas Urologicas Espanolas]. AB - In the absence of Spanish journals and publications with a high impact factor and since one of the primary reasons to obtain such an impact is the frequency with which the publication is referenced, we wanted to check the general belief by which even in the Spanish journals the proportion of national articles that get referenced is very small. We reviewed all articles published by Actas Urologicas Espanolas during 1989 and 1990 (12 issues, 246 articles with 4,549 references), and found that only 14.42% of references were from publications or books edited in Spain or at congresses held within Spain. After excluding books and communications originates in congresses, the figure is 10.9%. On the other hand, we noticed that over 25% articles do not include one single Spanish reference. Finally, the publication most often consulted is the USA Journal of Urology, which approaches some 20% of all mentions. PMID- 8368098 TI - [Ethical dilemmas in the field of genetics]. AB - After a brief introduction, the role of medical genetics in modern ethical conflicts is emphasized. International working approaches are discussed in an attempt to solve medical conflicts. The studies proposed by Wertz and Fletcher are reviewed in order to assess the strength of consensus on various working approaches. A brief discussion evaluates working approaches to ethical problems in genetics. This discussion also focuses on genetic counselling and screening questions regarding pertinent hereditary diseases. Final considerations point out the demanding role played by the modern geneticist in medical ethics perspectives now broadened by new insights, namely the challenge of human genome mapping. PMID- 8368100 TI - [Clinical course of primary non-obstructive megaureter: analysis of our series]. AB - Due to the widespread use of obstetrical ultrasonography with concomitant fetal screening, congenital uropathies are usually diagnosed in asymptomatic neonates. The main issue is to distinguish those cases of dilatation which are clearly obstructive and need surgical treatment from those which are within the normal anatomical range. Out of 47 patients with primary megaureter, 23 were nonobstructive, these are the aim of our study. There were 16 males and 7 females; 13 were located on the left side, 7 on the right side and 3 were bilateral, adding up to 26 reno-ureteral units. Prenatal diagnosis was performed in 16 cases, the eldest patient diagnosed was nine. All infants were evaluated with ultrasonography, voiding cystourethrography, excretory urography and diuresis renography. The latter has been the most important test inducing us to adopt a conservative attitude. Differential renal function was more than 40% in 24 units and in 2 was more than 35%. Diuretic renograms were type IIIa (Dilated non obstructed) in 19 cases and IIIb (Dilated partially obstructed) in 7. There were 2 cases with vesicoureteral reflux in the contralateral system. We have performed ultrasonography and diuresis renography during the follow-up. There were 8 cases with type I (Normal) renograms and 17 cases with type IIIa. Only one patient developed an obstruction and was operated on. In every case differential renal function did not deteriorate. In 9 cases urography was performed in order to see the anatomical changes. They have remained asymptomatic during the follow up except for two cases which presented urinary tract infection. BUN, creatinine and other biochemical figures remained within normal ranges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368101 TI - [Lymphatic staging by laparoscopic surgery]. AB - Lymphadenectomy is mandatory in vesical and prostatic tumours for a precise staging of candidates to radical surgery. Presentation of our series of 18 ilioobturative lymphadenectomies between May 1992 and February 1993, performed in 14 prostate carcinoma and 4 vesical tumours. As most interesting results, the average number of nodes removed, which was 8, and the discovery of nodular affectation in 5 cases, understaged by the non-invasive procedures, are highlighted; likewise, the reduction in surgery duration up to the current frame of 80 to 120 minutes must be emphasized. Mortality due to the procedure was null. We believe that laparoscopic lymphadenectomy should be the choice technique in the staging of tumoral dissemination in the ilioobturative domain. PMID- 8368102 TI - [Giant liposarcoma of the spermatic cord]. AB - Liposarcomas (LS) are malignant mesenchymal tumours which develop in fatty tissues. They are basically found at the retroperitoneum where they are relatively frequent in adults. The most common type is myxoid LS which, although less malignant, has like any other LS a high incidence of local relapses. Primary myxoid liposarcoma of the spermatic cord is an unusual, low-aggressiveness tumour. Under natural development, it can reach large dimensions with only local symptomatology. Pre-operative diagnosis of the paratesticular tumour is often difficult to establish, cuenca the teste suenate be differentiated from the tumoral mass by physical examination. A diagnostic approach of paratesticular tumours, scarcely reported in the literature, can be made by means of a vascular study with radionuclides. The choice therapy is surgical, through orchiectomy and extensive local removal. Considering the frequency of local relapse of myxoid liposarcoma, long-term follow-up is recommended. This paper reports the unusual presentation of one case of primary myxoid LS of the spermatic cord with an intrascrotal mass of 38 x 24 cm weighing 4,950 gr which is exceptional not only because of the site's infrequency but also for its size. PMID- 8368103 TI - [Acute urinary retention of psychogenic cause in a girl]. AB - Psychogenic acute urine retention is not as common as once was thought to be, but even more infrequent is its presentation in children. Explanation of one case of psychogenic acute urine retention (A.U.R.) in a female child, including analysis of diagnosis and treatment. PMID- 8368104 TI - [Testicular seminoma manifested by carcinomatous neuropathy: an unusual presentation. Review of the literature]. AB - Contribution of one patient with tetraparesic picture originated by a major sensory-motor neuropathy, due to paraneoplastic syndrome produced by a testicular seminoma. The patient underwent inguinal orchiectomy and radiotherapy, with favourable evolution of his neurological symptomatology. Review of the literature and confirmation of the extraordinary rarity of such clinical picture. PMID- 8368105 TI - [Renal abscess in patients diagnosed with AIDS and disseminated tuberculosis]. AB - Presentation of two cases of renal abscess formation in patients with stage IV C 1 AIDS and active associated tuberculosis. The microorganism isolated in the first case was S. aureus. Culture of the second cases was artefacted since antibiotic administration had already been started. Also, both patients showed abdominal abscesses, at spleen and liver level in the first case, and prostatic level in the second case, both compatible with Mycobacterium tuberculosis dissemination. Both cases showed a lethal evolution. The role played by the immunodeficiency as a precipitating agent in the extrapulmonary tuberculosis and in the formation of renal abscesses is analyzed. PMID- 8368106 TI - [Ureteral endometriosis. Review of the literature]. AB - Ureteral endometriosis is an uncommon process. It should be suspected, however, in patients with known pelvian disease presenting urological sings and symptoms. It is important to establish early diagnosis which does not delay a conservative therapeutical approach, so as to avoid the progressive decline of renal function and, eventually, nephrectomy. Contribution of one case of extraluminar ureteral endometriosis fitting this hypothesis and review of the most appropriate etiology, sings and symptoms, diagnosis and therapeutical approach. PMID- 8368108 TI - [Laparoscopic exeresis of a completely duplicated kidney]. AB - During the '80s, laparoscopy in general has undergone an enormous boom as representative of minimally invasive surgery, urology standing out in that progression as the specialty leading the endoscopic approach both for the tradition and profusion of techniques developed. In Spain, major scope laparoscopic surgery started with lymphadenectomy in which we are the second Spanish and first Andalusian group to perform it. The experience accumulated by our group has allowed us to perform and present one case of laparoscopic nephrectomy, this being the first time in Andalusia and second in Spain that an Urology Unit develops this technique, the distinct feature being the presence of complete duplicity of the kidney. The procedure had no peri or post-operative complications and the patient was discharged four days later. We conclude that although presently the indications of renal exeresis for this procedure are limited, these will soon be expanded thanks to the urologists' concern, the accumulation of experience and the improvement of the instrumentarium. PMID- 8368107 TI - [Retrovesical hemangiopericytoma]. AB - The hemangiopericytoma is an uncommon variety of the mesenchymal tumour derived from pericapillary structures, most frequently located in limbs and exceptionally at the retroperitoneum level. Although macroscopically the aspect is benign, this tumour has a recognised ability for local invasion and distant dissemination. PMID- 8368109 TI - [Paratesticular tumor. Liposarcoma of the spermatic cord]. AB - Liposarcoma of the spermatic cord is a rare tumour typically presenting in elderly people. It tends to grow around blood vessels. Most of them have a low level of malignancy and relapses tend to be localized. Metastasis, when present, occur through the haematological route, lymph spread being very unusual. Pre operative diagnosis is infrequent and overall prognosis is good. The choice treatment is radical orchidectomy, while long-term follow-up of these patients is mandatory. When local relapses become evident, the choice treatment is extensive local excision, followed by optional adjuvant radiotherapy. Chemotherapy has not proven to be effective. This paper reviews the current literature and contributes one case of mixed liposarcoma of the spermatic cord. PMID- 8368110 TI - [Cytogenetic characteristics and of primary culture in multiple renal tumors]. AB - The incidence of multiple tumours in renal cancer ranges between 1 and 30%. In these cases, it becomes very difficult to differentiate between adenoma and carcinoma just by using conventional methods, particularly in borderline cases. We carried out primary cultures and subsequent cytogenetic studies in 2 patients with multiple renal cancer. Clonal numerical changes in the first case were: 3, 7, 16 and 17 trisomies, chromosome loss; and structural changes, del(1) (p34), del(2) (p16, p22). In the second case, clonal numerical changes were 7 trisomy and tetrasomy and loss of the Y chromosome. Both tumours were cytogenetically characterized as papillary renal tumours. The diagnostic approaches are discussed and the prognosis possibilities evaluated, using this method to evaluate them in multiple renal tumours. PMID- 8368111 TI - [Endometrioid carcinoma of the prostate. Report of a case]. PMID- 8368113 TI - [Shockwave cytotoxicity on neoplastic and non-neoplastic cells]. AB - Since initial application of high-energy shockwaves to treat renal lithiasis, their usefulness has been extended within both the clinical and experimental fields. Shockwaves cytotoxic action is determined by means of cell viability methods of vital staining exclusion and nucleoside uptake. Application of shockwaves on cell cultures is carried out by means of an electromagnetic lithotripter. High-energy shockwaves have had cytotoxic action both on non tumoral and tumoral cells, during "in vitro" experiments. The cytotoxicity produced by the shockwaves, however, is different in tumoral and non-tumoral cells, the viability inhibition being higher in tumoral cells. PMID- 8368112 TI - [Adrenal gland surgery. Review of 34 cases]. AB - Over the last few years, a better anatomical and functional knowledge of the adrenal glands has allowed us to diagnose and treat optimally most of these gland's conditions. A variety of medical (endocrinology, anaesthesiology) and surgical specialties have been used to this aim. This paper reviews the adrenal gland's diseases treated in our unit over the last 9 years. Pre-operative management, ways of approach, morbidity and mortality as well as results are analyzed and compared with those obtained by other authors. PMID- 8368114 TI - [Immunoprophylaxis of recurrence of T1 G2 bladder tumors with interferon alpha 2b]. AB - Assessment of results with -2b Interferon used as prophylaxis in 20 patients who underwent surgery for T1,G2 urothelial vesical tumours. Dosage was weekly intravesical instillation of 50 x 10(6) IU for three months and then monthly up to one year treatment. Mean follow-up was 17.20 months (4-41 months). Relapse rate over this time was 50%, all before 15 months, a relapsing ratio of 2.82% patients/month and a disease-free interval of 27.5 months. Chances of being disease-free at 30 months is 48.21%. Progression of disease, whether in grade or stage, was observed in 25% cases. No patient showed relevant changes or side effects during treatment, except for 5 patients who reported mictional symptoms mainly during the first 3 months, none of which required discontinuation of treatment. From the data obtained, it can be deduced that for the time being no reason justifies the use of -2b Interferon versus other conventional chemotherapeutical or immunotherapeutical (BCG) agents in the prophylaxis of this type of tumours. PMID- 8368115 TI - [Extracorporeal lithofragmentation and of direct contact. Development of mathematical models for calculating the energy and predicting the fragmentation]. AB - The present experimental 'in vitro' study pursues the development of mathematical equations which, prior to lithofragmentation, would allow to estimate the amount of energy required and to predict the degree of fragmentation for each of the different sources of energy. A total of 114 calculi with 6 different compositions were analyzed by conventional X-rays (Rx), computerized axial tomography (CT) and dual X-ray densitometry (DO). Calculi were then fragmented using 4 different types of energy: electrohydraulic (LEH), piezoelectric (LEP), ultrasounds (US) and pulse laser (LAS). The correlation between imaging techniques parameters on the one side, and the amount of energy used and degree of fragmentation obtained on the other one, allow with a multiple linear regression analysis, both to develop mathematical equations to estimate the amount of energy required, and to predict the fragmentation rate. PMID- 8368116 TI - [Renal retransplantation. Study of 91 cases]. AB - Review of 91 retransplantations performed at our hospital between 1975 and 1991. There were 82 second transplants and 9 third transplants. Survival of patients to undergo retransplantations continues to increase. Over the last year, 19.1% of our transplants were the 2nd or 3rd ones for some patients. Analysis of causes for graft loss, which essentially are of immunological and surgical nature. PMID- 8368117 TI - [Diagnostic effectiveness of CT and MR in local staging of renal tumors]. AB - The aim of this paper is to study the pre-operative staging of renal tumours, comparing CT and MR, and the imaging criteria used, examining the diagnostic efficacy for each of them. Thirty-four tumours were obtained from 29 patients. All cases were studied with CT and MR. To measure diagnostic efficacy, both for each technique and the criteria used in 2 different readings, a diagnostic performance curve (DPC) is calculated. Neither CT nor MR show infiltration of renal capsule. With regard to perinephritic fat, fascia and adjacent organ invasion, both techniques lead to overstaging, mainly CT. When applying more conservative reading criteria, the results are much improved, specially in relation to CT, although results with MR continue to be more favourable. MR is better to study vascular invasion, providing no false results. Of 22 tumours undergoing surgery, first option was the correct staging in 14 tumour with CT and in 16 with MR. When selecting the best imaging technique to stage renal tumours, MR allows a better and simpler radiologic reading. Nevertheless, considering the high correlation between CT and MR, CT can be used more reliably in institutions where no easy access to a MR unit is available. Both CT and MR overstage renal tumours. PMID- 8368118 TI - [Incidental renal adenocarcinoma: study on 54 cases]. AB - Between 1974 and 1992, both inclusive, 204 renal adenocarcinomas were treated in the Urology Unit of the '12 de Octubre' Hospital, of which 54 (26.4%) were diagnosed by chance. The relative frequency of these renal tumours has experienced a highly significant progressive increase, from 0 in the 1974-1978 interval, to 13.04% in 1978-1980, 14.7% between 1981-1983, 20.68% in 1984-1986, 37.84% in 1987-1990, to reach over the last three-year period of 1990-1992 the remarkable figure of 41.93%. There has been no differences regarding incidence by sex (50% males and 50% females). Mean age at presentation is 61.5 years, ranging from 23 to 78 years. The suspected pathological cause most frequently leading to carry out the study where renal carcinoma is accidentally diagnosed are gastrointestinal disorders (50% of cases). The most frequently used imaging diagnostic technique is ultrasound (50% cases), emphasising the gradual increase in the number of cases diagnosed by ultrasound or CAT during the course of the study. Carcinomas accidentally diagnosed by CAT are those with less volume in our series. Regarding tumour characteristics, it should be pointed out a higher occurrence in the right kidney (64.8%) and a most frequent location in the upper renal pole (48%). Mean tumoral volume was 126 cc, although that value has gradually dropped, so that now the mean volume of accidental tumours treated over the last 5 is being 91 cc. Most cases present low staging at the time of diagnosis, 81% being pT2 N0 M0. Current overall survival is 89% of all cases followed-up. PMID- 8368119 TI - [Spontaneous perirenal hematoma secondary to hydronephrosis in pelvic kidney]. AB - Contribution of one case of Spontaneous Perirenal Haematoma (SPH) secondary to hydronephrosis accompanied by lithiasis in pelvic kidney. SPH can result from multiple causes, the most frequent ones being renal tumours, most particularly angiomyolipoma and hypernephroma. Hydronephrosis is an uncommon cause of SPH, and very few cases are described in the literature. The present paper addresses the diagnostic usefulness of the various radiological tests as well as the therapeutical approach to be followed. PMID- 8368120 TI - [Ultrastructural study of the stromal component in urethral caruncle]. AB - The stromal component of the urethral caruncle (UC) comprises a mixture of inflammatory, vascular, and fibrotic phenomena. Although mastocytes are cell elements known to appear in relation with chronic inflammation, there is no data in the literature explaining their significance in UCs or their ultrastructure relation with fibroblasts. We postulate that this special form of intercellular attachment could play a role in this condition's pathogenesis. PMID- 8368121 TI - [Systemic lupus erythematosus (S.L.E.) and (lupoid) interstitial cystitis]. PMID- 8368122 TI - [Metastatic disease of the penis. Report of 3 cases]. AB - Metastatic lesions of the penis are uncommon, only some 200 cases having been reported in the literature. Priapism is the most frequent symptom, although increased penis size, ulceration and nodes formation have also been described; metastasis happens simultaneously in 20% cases while in 50% of cases they appear 2 years after initial diagnosis. Survival of untreated patients has not exceed 24 weeks, whereas treated patients have survived 47 weeks. PMID- 8368123 TI - [Leiomyosarcoma of the spermatic cord]. AB - Presentation of an uncommon paratesticular tumour, located in the spermatic cord and originated in the smooth muscle of the cremaster, deferent, or the cord's vascular structures. In 1966, KYLE in Canada reviewed 22 cases of paratesticular leiomyosarcoma from the English literature, and in 1984 PUTS in the Netherlands extended this catalogue to 39. TAKAHA in 1991 presented 18 cases found in the Japanese literature. The theory of malignant degeneration from a previously existing leiomyomatous tumour is generally accepted. This entity is clinically associated with a clear tendency to local relapse, which does not imply a worse prognosis, and with a high percentage of blood metastasis three years after exeresis. The choice therapy is oncologic inguinal orchiectomy. Radiotherapy and chemotherapy, as coadjuvant therapies, appeared to be more effective in children's than in adult's sarcoma. Prognosis of these neoplasias in the reviewed literature is highly variable, ranging between 10% and 62% survival at 5 years, possibly due to the diversity of therapies and the patient's stage at the time of diagnosis. PMID- 8368124 TI - Protein purification by dye-ligand chromatography. AB - Dye-ligand chromatography has developed into an important method for large-scale purification of proteins. The utility of the reactive dyes as affinity ligands results from their unique chemistry, which confers both the ability to interact with a large number of proteins as well as easy immobilization on typical adsorbent matrices. Reactive dyes can bind proteins either by specific interactions at the protein's active site or by a range of non-specific interactions. Divalent metals participate in yet another type of protein-reactive dye interactions which involve the formation of a ternary complex. All of these types of interactions have been exploited in schemes for protein purification. Many factors contribute to the successful operation of a dye-ligand chromatography process. These include adsorbent properties, such as matrix type and ligand concentration, the buffer conditions employed in the adsorption and elution stages, and contacting parameters like flowrate and column geometry. Dye ligand chromatography has been demonstrated to be suitable for large-scale protein purification due to their high selectivity, stability, and economy. Also, the issue of dye leakage and process validation of large-scale dye-ligand chromatography has been discussed. Reactive dyes have also been applied in high performance liquid affinity chromatographic techniques for protein purification, as well as non-chromatographic techniques including affinity partition, affinity membrane separations, affinity cross-flow filtration, and affinity precipitation. PMID- 8368125 TI - The role of enantioselective liquid chromatographic separations using chiral stationary phases in pharmaceutical analysis. PMID- 8368126 TI - Molecular biochromatography: an approach to the liquid chromatographic determination of ligand-biopolymer interactions. PMID- 8368127 TI - Aging, comorbidity, and breast cancer survival: an epidemiologic view. AB - This is a review of epidemiologic studies, which suggest that comorbidity (e.g., diabetes and heart disease) has an adverse effect on survival among women with incident, invasive breast cancer, adjusting for chronological age and stage of breast cancer at diagnosis. As part of this review, recent results are presented from a series of 463 breast cancer cases, identified through the Metropolitan Detroit Cancer Surveillance System. Women with two or more concurrent health conditions were 2.2 times more likely than breast cancer cases without comorbidity to die from their breast cancer over a four-year period (95% CI: 1.13, 4.18). Limiting heart disease was especially problematic. Recommendations are made for future research in this area. PMID- 8368128 TI - Cytogenetics and clinical correlations in breast cancer. AB - We describe an ongoing study examining the relevance of cytogenetic changes in primary and metastatic breast cancer. Tumors samples from breast cancer patients are karyotype using G-banding techniques, and all chromosomal findings, including the presence of structural and numeric clonal abnormalities, are documented in a dynamic patient data base. Information on essential clinical characteristics is collected, and patients are followed longitudinally for disease recurrence, progression, and survival. Statistical analyses will examine potential correlations between specific abnormalities and clinical features of the disease, and survival differences between patients will be examined as a function of karyotypic differences. We anticipate that this research will provide insights on the natural history of breast cancer and help direct the search for the underlying molecular mechanisms of tumor genesis and progression. PMID- 8368129 TI - Breast cancer: influence of endocrine hormones, growth factors and genetic alterations. PMID- 8368130 TI - Regulation of estrogen receptor expression in breast cancer. AB - One of the most prevalent of cancers, breast cancer, is characterized by hormonal control of its growth. Expression of the estrogen receptor (ER) in MCF-7 breast cancer cells appears to be a complex process involving multiple steps subject to hormonal regulation by estrogen. Treatment of MCF-7 cells with estradiol results in the suppression of estrogen receptor protein. By 6 hours, the receptor protein declined by about 60% from a level of approximately 3.6 to 1.2 fmol/micrograms DNA and remained suppressed for 24-48 hours. Similar results were obtained with an estrogen receptor binding assay. Estrogen treatment also resulted in a decrease of receptor mRNA to approximately 10% of control values by 6 hours. Estrogen receptor remained at the suppressed level for up to 48 hours. Transcription run-on experiments demonstrated a transient decrease of about 90% in receptor gene transcription after 1 hour. By 3-6 hours transcription increased approximately 2-fold and remained elevated for at least 48 hours. These data suggest that estrogen suppresses ER mRNA by inhibition of ER gene transcription at early times and by a post-transcriptional effect on receptor mRNA at later times. To determine whether post-transcriptional regulation of ER gene expression is mediated by an ER-dependent mechanism independent of protein synthesis, we used the competitive estrogen antagonist, 4-hydroxytamoxifen, and the inhibitor of protein synthesis, cycloheximide, to study the regulation of ER mRNA by estradiol. 4-Hydroxytamoxifen had no effect on the steady-state level of receptor mRNA and effectively blocked the suppression of ER mRNA by estradiol. The metabolic inhibitor, cycloheximide, was unable to prevent the estrogen induced decrease in ER mRNA. These data provide evidence that the post-transcriptional suppression of ER expression through estradiol is mediated through the ER independent of protein synthesis. PMID- 8368131 TI - Aging and development of ovarian epithelial carcinoma: the relevance of changes in ovarian stromal androgen production. AB - There are three types of ovarian neoplasms: (1) Those which arise from the surface epithelium covering the ovary. (2) Those which are derived from the cortical mesenchymal stroma. (3) Those which develop from germ cells. Our laboratory has concentrated its effort on solid tumors in women of the first type, epithelial, which has the highest incidence and is the most lethal. Development of these tumors is correlated with aging in the ovary. They form primarily during the perimenopause. Among women, 64% of the total ovarian cancer cases are diagnosed between ages 41 and 60 years. Our approach has been to establish stable tumor cell lines from patient specimens for use as in vitro models. We have investigated the response of these cells to steroid hormones because we hypothesized that these tumors retain some metabolic characteristics which are specific to the ovary. Our data demonstrate that testosterone and androstenedione, but not cortisol, inhibited proliferation of ovarian tumor cells in vitro by a mechanism which was independent of steroid receptors. These androgens are routinely synthesized and secreted by human ovary, and in the menopausal ovary the primary source of androgen is the stromal cell compartment. Because a relatively high local concentration of ovarian androgen exists in vivo, it is possible that androgen may suppress ovarian epithelial carcinoma in women as well. If it does, then development of this carcinoma may be facilitated when the postmenopausal ovary fails to produce adequate androgen during postreproductive years. PMID- 8368132 TI - Prostatic cancer: an age-old problem. PMID- 8368133 TI - Stromal-epithelial paracrine interactions in the neoplastic rat and human prostate. AB - Homotypic paracrine interactions in the rat and human prostate have been investigated using prostatic stromal cells and neoplastic epithelial cells (PA III, rat; TSU-pr1, human). Secretory proteins prepared from each cell type were used to determine the dose dependent regulation of growth (DNA synthesis) of the corresponding homotypic responder cell, as determined by 3H-thymidine incorporation. PA-III secretory protein stimulated rat stromal cell proliferation by 1.8-fold. This stimulatory activity of PA-III protein on stromal cell proliferation was partially reduced (approximately 35%) by treatment with nerve growth factor (NGF) antibody, whereas neither acidic fibroblast growth factor (aFGF) antibody nor basic fibroblast growth factor (bFGF) antibody immunoneutralized the stimulatory activity of PA-III cell protein. In the corresponding opposite interaction, rat stromal cell protein modulated PA-III growth in a biphasic manner. At lower concentrations of stromal cell protein (1.25 micrograms/ml) PA-III cell growth was stimulated by 1.6-fold, whereas at higher concentrations of protein (100 micrograms/ml) PA-III cell growth was inhibited to 60%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with NGF antibody reduced PA-III cell relative growth to approximately 30% and 5%, respectively. bFGF antibody treatment of stromal cell protein at 1.25 micrograms/ml did not influence relative growth, whereas bFGF antibody treatment of 100 micrograms/ml stromal cell protein reduced relative growth by an additional 40%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with aFGF antibodies reduced relative growth from that observed at these two protein concentrations by approximately 50% in both cases. Human epithelial TSU-pr1 protein stimulated human stromal cell proliferation approximately 1.7-fold. Treatment of TSU-pr1 protein with NGF antibody resulted in stimulation of human stromal cell proliferation (4-fold). In the corresponding opposite interaction, human stromal cell secretory protein stimulated TSU-pr1 epithelial cell proliferation in a dose-dependent manner up to a maximum of 2.6-fold. This stimulation of TSU-pr1 proliferation by stromal cell secretory protein was reduced to 20% of maximal levels by treatment with antibody against NGF, whereas antibodies against bFGF and aFGF did not significantly influence the stimulatory effect of stromal cell secretory protein mediated proliferation of TSU-pr1 cells. These results suggest that prostatic stromal cells and neoplastic epithelial cells secrete several paracrine factors. One of these factors is nerve growth factor-like, and appears to have a major non neurotrophic influence on the paracrine regulation of prostatic growth. PMID- 8368134 TI - Age related changes in adults with acute leukemia. PMID- 8368135 TI - Significance of chromosomal changes in patients of different age groups with acute leukemia. AB - Chromosome abnormalities have been observed in about 50% of patients with acute leukemia. There have been several published reports which emphasized the chromosomal changes in relation to the age of the patient and the morphologic type of acute leukemia. All observations suggest that there are both age related similarities and differences. The karyotype is an important independent prognostic factor in acute leukemia; however, age alone (especially above age 70) is the single most important factor for a poor prognosis. PMID- 8368136 TI - Glucocorticoid receptors in leukemias, lymphomas and myelomas of young and old. AB - In this paper we have briefly reviewed the nature of leukemias and lymphomas in the old and the young. We surveyed in general the ways in which lymphoid cells and other hematologic elements respond to glucocorticoids, mentioning that there may be direct or indirect effects on their growth by these ligands. We have reviewed the current general model for the action of glucocorticoids in all cells, namely the fact that the actions of these steroids are mediated to a large extent through binding with ligand-activated transcription factors, their receptors. The growing wealth of detail about the nature of the interaction of these receptors with regulatory sites in the genome is discussed. Finally, we have described our results with lines of tissue culture cells representing clones from a typical leukemia of the young, and of myeloma, a typical hematologic malignancy of the elderly. Several features of the effects of glucocorticoids on these cells point up areas that would be pertinent to explore in aging and in the relationship of hematologic diseases to survival and response to therapy in the older versus the younger patient. PMID- 8368138 TI - General aspects of cancer chemotherapy in the aged. PMID- 8368139 TI - Summation and synthesis: from the cancer cell biology point of view. PMID- 8368137 TI - Genetic and molecular basis for cellular senescence. AB - Normal human and rodent cells in culture exhibit a finite life span at the end of which they exhibit morphological changes and cease proliferating, a process termed cellular senescence or cellular aging. Many cancer cells differ from normal cells in that they do not senesce and have an indefinite life span in culture, suggesting that alterations relating to cellular senescence are involved in the neoplastic evolution of tumor cells. Recent experimental results strongly support a genetic basis for cellular senescence. Defects in the senescence program in transformed cells can be corrected by introduction of a specific chromosome from normal cells into the abnormal cells. Using this approach, possible senescence genes have been mapped to specific chromosomes. Cell cycle control genes that regulate entry into the DNA synthetic phase of the cell cycle must be altered in senescent cells. Recent findings suggest that phosphorylation of the retinoblastoma gene is altered in senescent cells. It is possible, but not yet proven, that aging at the cellular level contributes to the aging of the individual. Therefore, an understanding of cellular senescence at the genetic and molecular levels may provide new insights into both the cancer and aging processes. PMID- 8368140 TI - Summation and synthesis: from the immunology point of view. PMID- 8368141 TI - Summation and synthesis: from the aging point of view. PMID- 8368142 TI - A single gene change can extend yeast life span: the role of Ras in cellular senescence. AB - The budding yeast Saccharomyces cerevisiae has a limited life span (reproductive capacity), which is measured by the number of times an individual cell divides. There is evidence for the involvement of a senescence factor that affects cell cycle traversal in older yeast cells. Distinct alterations in the abundance of a handful of transcripts have been identified during the life span of this organism, and the genes that specify these mRNAs have been cloned. This raises the question whether the activity of one or more genes can alter the yeast life span. Indeed, the controlled expression of the transforming gene of Harvey murine sarcoma virus (v-Ha-ras) was found to extend the life span nearly two-fold. The normal homologs of this oncogene, RAS1 and RAS2, play a central role in the integration of cell growth and the cell cycle in yeast. Expression of v-Ha-ras appears to impinge on this integration. We suggest that it is the relative levels of the senescence factor and the Ras protein that determine whether a cell ceases to divide and senesces. We liken the senescence factor to the product of an anti oncogene or tumor suppressor gene that neutralizes Ras. PMID- 8368144 TI - Tumors and aging: the influence of age-associated immune changes upon tumor growth and spread. PMID- 8368143 TI - A comparison of the properties of human p53 mutant alleles. PMID- 8368146 TI - Introduction: sphingolipids and their metabolites in cell regulation. PMID- 8368145 TI - T cell differentiation and functional maturation in aging mice. PMID- 8368147 TI - The role of sphingosine in cell growth regulation and transmembrane signaling. PMID- 8368148 TI - Verotoxins and their glycolipid receptors. PMID- 8368149 TI - Glycosphingolipid tumor antigens. AB - Tumor-associated glycosphingolipids are a common finding in human tumors, and monoclonal antibodies directed to defined carbohydrate epitopes of these structures have been developed. A majority of the glycosphingolipid antigens are of the lacto series, types 1 and 2, and these epitopes are often also found on glycoproteins. The tumor-associated gangliosides of the ganglio series, preferentially found in tumors of neuroectodermal origin, have binding epitopes that have not been detected in glycoproteins. A large number of monoclonal antibodies, mainly murine but some human, have been produced, and their epitope specificity defined. These antibodies have been used for investigation of the role of tumor-associated glycosphingolipids in tumor cells. Some antibodies have been shown to inhibit the growth of tumor cell lines in vitro and in vivo and to influence the adhesion properties of tumor cells, and some antibodies have been shown to give a clinical response. Tumor cell lines are commonly used in tumor biology studies, but the expression of tumor-associated glycosphingolipids in tumor cell lines does not always reflect their expression in the tumor tissue from which the cell line originates. The expression of tumor-associated glycosphingolipids has also been shown to be different in cells grown in vitro or as solid tumors in nude mice or rats. In conclusion, monoclonal antibodies specific for tumor-associated glycosphingolipids may be valuable tools in diagnosis and, in addition, in therapy, glycosphingolipids may also be used in active immunotherapy. The availability of these antibodies also opens the possibility of studying the biological function of glycosphingolipids and may then lead to new approaches for the improved diagnosis and therapy of human tumors. PMID- 8368150 TI - Gangliosides and modulation of the function of neural cells. PMID- 8368151 TI - The sphingomyelin cycle: a prototypic sphingolipid signaling pathway. PMID- 8368152 TI - The role of glycosphingolipids in hypoxic cell injury. AB - Recent advances in the understanding of the molecular mechanism of cell injury have led to the realization that cell injury is a gradual process, which involves, in its early stages, specific biochemical responses of cells to the injury process. In this review, we have shown that the pursuit of the mechanisms by which inhibition of a specific GSL (GalCer) in hypoxic OLG occurs can lead to (1) an understanding of how the synthesis and transport of GalCer are regulated in the cell, and (2) evidence that the injury causes a potentially devastating (yet reversible) block in the production of this important lipid. This review has also discussed evidence that GSL, in their roles as regulators of the cell's interaction with its environment, can play important roles in determining the outcome of injurious processes. PMID- 8368153 TI - Bioactive gangliosides: differentiation inducers for hematopoietic cells and their mechanism(s) of actions. PMID- 8368154 TI - Ceramide: a novel second messenger. AB - The data discussed in the preceding sections suggest that information may be transmitted both through synthesis and through degradation of sphingomyelin. Although the sphingomyelin pathway holds promise as a new signaling system coupling TNF receptor activation to cellular stimulation (Fig. 5), the work is still at a preliminary stage. A physical association of receptors with neutral sphingomyelinase has yet to be established and the ceramide-activated protein kinase has yet to be isolated. Endogenous substrates for the kinase have also to be identified. Furthermore, the exact role of this pathway has not been defined. It is unclear whether this pathway is specific to monocyte differentiation or cytokine action. It also seems unlikely that a single signal transduction mechanism can account for all the diverse effects of TNF-alpha in different systems (Vilcek and Lee, 1991). Interactions with other signaling systems are sure to complicate elucidation of the exact role(s) of this pathway. Nevertheless, availability of cell-permeable analogs of ceramide, localization of many components of the system at the cell surface, and recent development of anti TNF receptor antibodies to receptor isotypes may allow for greater definition of the sphingomyelin pathway in the near future. PMID- 8368155 TI - Occupational asthma--a model to study the natural history and pathogenic mechanisms in asthma. AB - Occupational agents can give rise to asthma either through producing specific IgE antibodies or through some as yet unidentified immunological mechanism. Study of pathogenic mechanisms of occupational asthma can generate very useful information on the pathogenesis of nonoccupational asthma. Occupational asthma also provides an ideal model to study the natural history of asthma. As the agent responsible for asthma is known, it is possible to design a study to investigate predisposing host factors and level of exposure and their interaction in determining the onset, the severity, and the outcome of the disease. PMID- 8368156 TI - Isocyanate induced lung disease. AB - A review of the pathogenesis of isocyanate induced lung disease is given with an emphasis on immunologic mechanisms of disease. PMID- 8368157 TI - Recombinant Aspergillus fumigatus allergen I/a (rAsp f I/a) in the diagnosis of Aspergillus related diseases. AB - A. fumigatus allergen I/a (rAsp f I/a) was produced in Escherichia coli, affinity purified by Ni(2+)-chelate chromatography and refolded. rAsp f I/a binds IgE of A. fumigatus-allergic individuals as shown by ELISA, dot blots and Western blots. In addition, rAsp I/a elicited positive immediate type I skin reactions in individuals allergic to A. fumigatus but not in control individuals. Hence, rAsp f I/a can be used as a standardized antigen/allergen for an improved serological and clinical diagnosis of A. fumigatus-associated diseases. PMID- 8368158 TI - The role of cell adhesion molecules in asthma--an overview. PMID- 8368159 TI - Efficacy of monoclonal antibodies against adhesion molecules in animal models of asthma. AB - Cell surface adhesive glycoproteins are principal regulators of nearly all aspects of immune/inflammatory responses. Using monoclonal antibodies to individual adhesion molecules, the expression and contribution of specific molecules in the pathogenesis of allergen-induced airway hyperresponsiveness in monkeys has been deciphered. Results confirm the importance of cell adhesion and demonstrate that antagonism of a single adhesion molecule may provide a novel therapeutic approach. PMID- 8368160 TI - Adhesion proteins on airway eosinophils in allergy and asthma. AB - Adhesion to, and interaction with, airway endothelium, interstitial matrix and epithelium during migration to the allergen-challenged airways of allergic rhinitis and asthma patients may account for the observed functional upregulation (priming) of airway eosinophils compared with corresponding blood eosinophils. PMID- 8368161 TI - Strategies for in vivo blocking of adhesion molecules. PMID- 8368162 TI - Cytokines in allergic inflammation. PMID- 8368163 TI - Eosinophils and cytokines. AB - Cytokines act on eosinophils to regulate eosinophil function, with IL-5 recognised to be especially important in control of eosinopoiesis, eosinophil survival and eosinophil priming. In addition, eosinophils have the capacity to produce cytokines involved in acute and chronic inflammatory and repair processes, as well as to produce cytokines that stimulate eosinophils within an autocrine loop. This paper describes (A) an immunomagnetic selection technique for the purification of human blood eosinophils, and (B) a method that employs immunofluorescence with flow cytometry for measurement of blood and sputum eosinophil surface markers. Having demonstrated that sputum eosinophils express HLA-DR, highly purified blood eosinophils were used to analyse (C) the induction and function of eosinophil HLA-DR. Cytokines have the capacity to induce eosinophil HLA-DR, and are produced by eosinophils as an accessory function during antigen presentation. Finally, preliminary data on (D) eosinophil production of IL-8 is presented. Hence, eosinophils have the capacity to act as immunomodulatory cells within cells networks in allergic and asthmatic inflammation. PMID- 8368164 TI - Mast cell cytokines in allergy and inflammation. AB - Recent findings indicate that mast cells can influence biological responses through the production of cytokines and suggest that many allergic reactions and other biological processes may be regulated by a "mast cell-leukocyte cytokine cascade". This hypothesis proposes that certain biological responses are initiated by mast cell activation, resulting in the mast cell-dependent release of TNF-alpha and other cytokines which can promote the recruitment of eosinophils, neutrophils, and other effector cells. The recruited effectors then influence the progression of the response by providing additional sources of some cytokines which also can be elaborated by mast cells, as well as by producing other cytokines not known to be of mast cell origin. PMID- 8368165 TI - Bronchial hyperreactivity and eosinophil granule proteins. AB - Five lines of evidence support the hypothesis that the eosinophil, possibly through its granule proteins, mediates bronchial hyperreactivity. First, bronchial hyperreactivity and blood eosinophilia are associated in patients with asthma. Second, bronchial hyperreactivity is associated with the number of eosinophils and the levels of eosinophil granule MBP in BAL fluids. Third, direct instillation of MBP into the lungs of monkeys caused bronchospasm and increased reactivity to methacholine. Fourth, direct application of MBP to respiratory epithelium caused increased smooth muscle reactivity to acetylcholine, suggesting that MBP stimulates respiratory epithelium to produce factors active on smooth muscle. Fifth, MBP causes allosteric inhibition of lung M2 muscarinic receptors. PMID- 8368166 TI - Is airways hyperreactivity selective or non-selective? AB - Airways hyperresponsiveness has often been termed "nonspecific" on account of close correlations between responses to histamine and methacholine. This relationship, however, does not apply to stimuli, such as exercise, hyperventilation, sulphur dioxide, and distilled water. We have shown that allergen causes a greater and more prolonged increase in responses to bradykinin than to methacholine adding support to the notion that airways hyperresponsiveness is a selective pathophysiologic abnormality. PMID- 8368167 TI - Muscarinic receptor subtypes: implications for therapy. AB - At least three subtypes of muscarinic receptor have been localised to human airways. M1-receptors facilitate ganglionic transmission and therefore enhance cholinergic reflexes, M2-receptors are localised to post-ganglionic cholinergic nerve terminals and inhibit the release of acetylcholine and M3-receptors on airway smooth muscle mediate constriction and on submucosal glands mediate increased mucus secretion. M3 or mixed M1/M3-receptor antagonists should be preferable to the non-selective anticholinergic drugs in current use, since they would not increase acetylcholine release from cholinergic nerves. PMID- 8368168 TI - (+/-) isoprenaline revisited: adverse effects of sympathomimetics in asthma. AB - It is a matter of concern that regular, excessive use of contemporary sympathomimetics has been associated with morbidity and mortality from asthma. As a consequence, restrictions on sympathomimetic usage have recently been advocated in asthma management guidelines. he association between excessive use of inhaled (+/-)isoprenaline and an epidemic of asthma deaths in the 1960s provides a precedent; hence, we have reviewed the numerous clinical and experimental reports concerning (+/-) isoprenaline to provide insight into the present controversy. PMID- 8368169 TI - Anomalous bronchospasm following inhalation of (+) isoprenaline by asthmatics. AB - Sympathomimetics (beta-adrenergic agonists) presently used in asthma therapy comprise racemic mixtures of bronchodilator and non-bronchodilator enantiomers. In a randomized, double-blind placebo-controlled study, asthmatic subjects inhaled a nebulized solution of the non-bronchodilator (+) enantiomer of isoprenaline. Substantial decreased forced expiratory volume (FEV1) was detected in 2 patients and of the remaining 8, a single subject had increased reactivity to histamine 7 h after inhalation of (+) isoprenaline. These effects of (+) isoprenaline may contribute to anomalous effects of (+/-) isoprenaline in asthma. PMID- 8368170 TI - Noninvasive methods to examine the anti-inflammatory effects of drugs. AB - The anti-inflammatory effects of drugs can be studied non invasively using sputum which has either been produced spontaneously or induced with hypertonic saline. We have developed an efficient semi-automated method to examine sputum which should be widely applicable. This approach is recommended to provide a direct sampling of the airway secretions to study the inflammatory process and to demonstrate drug effects. We have validated a method to prospectively induce a mild exacerbation of airway inflammation by controlled reduction of inhaled steroid in steroid-dependent asthmatics. This can be used to examine the ability of drugs to prevent or reverse airway inflammation. PMID- 8368172 TI - Atopy and the environment. PMID- 8368171 TI - Methods for evaluation of anti-asthma drugs in the primate. AB - Use of the primate is gaining popularity in the definition of anti-asthma drugs. The present report describes three novel tests of (1) bronchodilatation, (2) hyperreactivity and (3) anti-inflammatory activity in the rhesus monkey. All tests are based on standard clinical techniques and the relevance and application of the tests to subsequent clinical evaluation is addressed. PMID- 8368173 TI - Air pollution and airway epithelial cells. AB - Recent epidemiological evidence suggests that air pollution, resulting from vehicle exhaust emissions and burning of liquid petroleum gas or kerosene, may play an important role in the development of allergic airways disease. Further, agents such as O3 and NO2 are thought to be major proponents of disease and act by damaging the airway epithelium. It is hypothesised that this pollution-induced damage results in the generation of mediators which lead to inflammation and possibly airway hyperreactivity. PMID- 8368174 TI - The immunology of extrinsic and intrinsic asthma. AB - It is now widely accepted that chronic mucosal inflammation plays an important role in the pathogenesis of asthma. This response involves the interaction of various cell types and is not the result of a single inflammatory cell acting in isolation. The present review describes the possible role of T lymphocytes in the inflammatory response of extrinsic (allergic) and intrinsic (nonallergic) asthma, focusing mainly on analysis of lymphocyte subpopulations, their activation state and cytokines produced in peripheral blood and bronchoalveolar lavages. Recent research suggests that there may be fundamental immunological differences between intrinsic and extrinsic asthma. In particular, intrinsic asthmatics have different patterns of T cell activation and cytokine production. PMID- 8368175 TI - [A case of Duane's syndrome with ocular melanosis]. AB - Duane's syndrome has various ocular and systemic abnormalities. We report a Duane's syndrome patient with ocular melanosis. Duane's syndrome has many complications, but ocular melanosis has never been reported previously. It is possible that there is a similar mechanism between the ocular melanosis and misdirection of the oculomotor nerve to the external rectus in this case, but it is more probable that it is simply coincidental. PMID- 8368176 TI - [Corneal epithelium]. PMID- 8368177 TI - [Transforming growth factor-beta (TGF-beta) inhibits epithelial wound healing of organ-cultured rabbit cornea]. AB - Transforming growth factor-beta (TGF-beta) is a unique polypeptide growth factor which has been found to stimulate mesenchymal cell proliferation and inhibit epithelial cell growth. Whether or not TGF-beta inhibits corneal epithelial wound closure remains controversial. This study evaluated the effects of TGF-beta on corneal epithelial wound healing in vitro. Rabbit corneas with an artificial 8 mm epithelial defect were organ-cultured for 48 hr in TC-199 supplemented with TGF beta (100 pg/ml, 1 ng/ml, or 10 ng/ml). The contralateral eye served as control. TGF-beta at 1 ng/ml and 10 ng/ml concentrations showed significant decrease in wound-healing rate compared with the control. 5-bromo-2'-deoxyuridine immunohistochemistry showed a significant decrease in S-phase cell count in the 1 ng/ml group compared with the control. These results strongly suggest that TGF beta inhibits corneal epithelial wound healing. PMID- 8368178 TI - [Corneal epithelial wound healing in the denervated eye]. AB - We investigated the rate of corneal epithelial wound healing in rabbits which had undergone surgical trigeminal denervation. Seven New Zealand albino rabbits underwent unilateral neurotomy of postganglionic trigeminal nerves via intracranial route. At 14 days after operation, 10 mm diameter central corneal epithelial defects were created in both eyes by n-heptanol. The area of epithelial defect was then photographed at 12-hour intervals and the epithelial healing rate was calculated (1st experiment). At 14 days after epithelial wound closure, the corneal epithelium was again denuded in a similar fashion (2nd experiment). The epithelial healing rate of the denervated and control eyes respectively were 1.28 +/- 0.25 and 1.39 +/- 0.31 (mm2/hr) in the first experiment, and 1.05 +/- 0.20 and 1.44 +/- 0.22 (mm2/hr) in the second. There was a statistically significant difference in the epithelial healing rate between the two groups in experiment 2 (p < 0.05), These results indicate that corneal epithelial wound healing is impaired in the denervated eye. PMID- 8368179 TI - [Experimental retinal branch vein occlusion. 4. Pathological changes in the middle and late stage]. AB - Retinal branch vein occlusion in macaca monkeys (Macaca irus) was produced by dye laser photocoagulation, and observed histopathologically from five days to one year after photocoagulation. Ten days later, retinal edema and hemorrhage observed at an early stage gradually decreased. Two weeks later, capillary bed closure areas were observed in fluorescein angiography. The capillary closure was not reversible when disturbance of the retinal circulation continued for more than three or four days after photocoagulation. Three months later, dry retina was observed in the capillary bed closure areas. One year later, the retina was severely degenerated and thinned. In these retinal areas, capillary lumens observed microscopically were occluded by cellular components. Sheathing of large veins was observed in these retinal areas. The walls of these large veins were thick and fell into hyaline degeneration. Their lumens were narrowed or obstructed. During the period of observation, retinal neovascularization was not observed. PMID- 8368181 TI - [Equivalent ultrasonic velocity for intraocular lens implanted eyes in A-mode biometry]. AB - With the standard ultrasonic velocity in commercially available instruments, there is a large difference of the ultrasonic velocity between the ocular medium and the implanted intraocular lens (IOL). If the PMMA or silicon IOL-implanted eye is assessed by using the ultrasonic velocity of the phakic or aphakic eye (1,550 m/s or 1,532 m/s), the error induced by the mismatch of the velocity is considerable. Therefore, we estimated the axial length error of pseudophakic eyes in ultrasonic biometry, and also derived theoretically the overall average sound speed (equivalent ultrasonic velocity, EUV) in IOL-implanted eyes. We found that the EUV (VE) can be estimated from the equation, VE = LV1V2/ T(V1-V2)+LV2], where L is the axial length of the eye, V1 the ultrasonic velocity of aqueous and vitreous body, V2 the ultrasonic velocity of the IOL, and T the central thickness of the IOL. The EUV for a PMMA IOL-implanted eye is approximately 1,560 m/s, and the EUV for a silicon IOL-implanted eye is approximately 1,500 m/s in an eye of standard length (24 mm) and an IOL of standard central thickness (1 mm). However, the EUV is a function of the axial length of the eye (L), the central thickness of the IOL (T), and the sound velocity in the implanted IOL (V2), and thus the EUV can not be applied for all cases. To perform more accurate ultrasonic biometry in pseudophakic eyes, we should rectify the apparent axial length assessed by the aphakic sound speed (1,532 m/s) with the central thickness of the implanted IOL. PMID- 8368180 TI - [Evaluation of the effect of the sodium hyaluronate ophthalmic solution on tear film stability--non-contact specular microscopic evaluation]. AB - Sodium hyaluronate solution is known to relieve various dry eye symptoms by suppressing the breakup of the preocular tear film. Using tear film stability as a parameter, we examined in 12 volunteers the time and concentration-dependent effects of sodium hyaluronate on their short precorneal tear film breakup time (BUT, 10 sec. or less) at a low tear volume (15 mm or less by using the phenol red thread test). Each subject underwent four separate study periods, receiving one of the following four ophthalmic solutions during each period: 0.05, 0.1, 0.3% w/v sodium hyaluronate (molecular weight, about 1,000,000) or the vehicle alone. BUT was measured non-invasively using a non-contact specular microscope before and 5, 15, 30, 60, 120, and 180 minutes after drug application. While BUT was not significantly prolonged after instilling either the vehicle or 0.05% solution, it was significantly increased at all times after applying either 0.1% or 0.3% solution, as compared to preinstillation. These results indicate that sodium hyaluronate solutions at concentrations of at least 0.1% can be effective in alleviating symptoms of dry eye. PMID- 8368182 TI - [Risk factors for occurrence and progression of diabetic retinopathy]. AB - The risk factors for the occurrence and progression of diabetic retinopathy were estimated in 1084 diabetic subjects (4358 person-years) by logistic regression analysis. The diabetic duration, the average of HbA1C for every year of observation, the range of HbA1C, the difference of HbA1C between the first visit to our clinic and the average of one year of HbA1C were statistically significant covariates for the risk of the occurrence of retinopathy. The relative risks of the occurrence of retinopathy as compared with the diet were estimated as 2.02 in oral administration of medicine and 1.86 in insulin therapy. The interaction between the difference of HbA1C and the average of HbA1C was statistically significant for the progression of retinopathy. When the response surface was estimated, the risk of progression of retinopathy differed greatly according to the blood glucose control level. PMID- 8368183 TI - [Prevalence of diabetic ocular complications and systemic factors]. AB - The prevalence of diabetic ocular complications and the correlation between diabetic retinopathy and systemic factors were examined in 2,300 cases (4,600 eyes) with non-insulin-dependent diabetes mellitus. The prevalence of cataract was 66.7%, of retinopathy 37.0%, of refractive and accommodative change 6.2%, of glaucoma 1.9% (rubeotic glaucoma was 1.0%), of rubeosis iridis 1.5%, of iridocyclitis 0.8%, of extraocular muscle palsy 0.2%, and of ischemic optic neuropathy 0.1%. Duration of diabetes mellitus, HbA1C value, methods of diabetic control, age, diabetic nephropathy, diabetic neuropathy, hypertension, systolic blood pressure, diastolic blood pressure, and arteriosclerosis obliterans were related with diabetic retinopathy. We suggest that the management of diabetic patients needs sufficient attention in the cases with oral administration of medication, insulin therapy, and diabetic nephropathy. PMID- 8368184 TI - [Evaluation of tissue plasminogen activator and plasminogen activator inhibitor-1 in blood obtained from patients of idiopathic central serous chorioretinopathy]. AB - It is postulated that idiopathic central serous chorioretinopathy (ICSC) may be induced by a variety of underlying choroidal diseases capable of producing initially alterations in the permeability of the choriocapillaries. A history of unusual emotional stress frequently accompanies the onset of visual complaints. We have reported that alterations of serum lipids may exert a powerful effect on tissue plasminogen activator (t-PA) levels acting as a risk factor of variable cardioangiopathies. In this study, we evaluated the levels of t-PA activity, t-PA antigen and plasminogen activator inhibitor-1 (PAI-1) in blood from the patients with central serous chorioretinopathy, and compared them with the levels of total cholesterols (TCH), triglycerides (TG), and high-density lipoprotein cholesterol (HDL). t-PA activity levels and HDL were lower than in standard controls but t-PA antigen, PAI-1 antigen, and TG were higher. These facts may be associated with the pathogenesis or pathophysiological features of ICSC. PMID- 8368185 TI - [Analysis of blood flow velocity in the ophthalmic artery by color Doppler imaging. 2. Studies on diabetic eyes]. AB - Color Doppler imaging was used to investigate the changes in Pourcelot index (RI), which is an index for vascular resistance calculated from the blood flow velocity of the ophthalmic artery, related to the complications of diabetes mellitus (diabetic retinopathy, diabetic nephropathy) and systemic background (duration of diabetes mellitus, value of hemoglobin A1C (HbA1c)) in 46 diabetic patients and in 20 normal subjects. RI was significantly higher in diabetic patients than in normal subjects (p < 0.05). RI increased in patients without retinopathy (p < 0.05), in patients with background retinopathy (p < 0.05), and in patients with preproliferative or proliferative retinopathy (p < 0.05), but it did not change in patients after panretinal photocoagulation, compared with the normal subjects. In diabetic patients, RI was higher (p < 0.05) in patients with nephropathy than in those without nephropathy. The time from onset of diabetes mellitus and the value of HbA1c had no correlation with RI. Our results indicate that choroidal circulation was changed in diabetic patients compared with normal subjects and that the changes were related to diabetic nephropathy. PMID- 8368186 TI - [Lipoprotein (a) and sclerotic changes in retinal arterioles]. AB - Lipoprotein (a) (Lp(a)) has been considered an independent risk factor for arteriosclerotic disease and its role in retinal vascular changes was studied in this report. The study was made on 160 patients of age 54 and above. They were divided into four groups depending upon their clinical background with or without the presence of diabetes mellitus (DM) and cerebral infarction (CI). The retinal vascular status of the patients was studied by ophthalmoscopic examination and the findings were graded according to Scheie's classification. We found that all the patients with retinal arterial hypertension and arteriosclerosis had a significant by high level of serum Lp (a). Similarly, serum Lp (a) level was higher in the patients with DM and CI than in the control subjects. These findings suggested that Lp (a) might influence the pathological changes of senile retinal arterioles. Moreover, we found a positive linear correlation between Lp (a) and plasminogen in patients with CI. PMID- 8368187 TI - [Inferior oblique underaction]. AB - We investigated the etiology and incidence of 100 cases of inferior oblique underaction. The difference between congenital and acquired underaction was discussed using Awaya's New Cyclo Tests (NCT) to examine cyclodeviation qualitatively and quantitatively. Inferior oblique underaction had been considered more frequently congenital than acquired. However, 63.0% of our cases were proved to be acquired. The congenital cases were Brown's syndrome and cases of unknown causes and the acquired cases were mainly of myasthenic or traumatic origin. The results of the NCT examination were as follows: incyclodeviation or no cyclodeviation was encountered in all cases of congenital underaction except for one postoperative case, but excyclodeviation rather than incyclodeviation occurred in cases of acquired underaction, which showed ocular torticollis to the side of the paretic eye. This result suggested that some other muscles were involved in acquired cases of seemingly isolated inferior oblique underaction, especially in myasthenia gravis. A diagnosis of myasthenia gravis should be considered first when an acquired inferior oblique underaction occurs with association of excyclodeviation demonstrated by the NCT as well as Cogan's lid twitch sign. PMID- 8368188 TI - [Study of retinal correspondence in esotropia with phase difference haploscope]. AB - There is some concern regarding the evaluated depth of anomalous correspondence, because we often experience paradoxical results. We have already reported that, in intermittent exotropia, we sometimes found dual correspondence with a phase difference haploscope (PDH) reducing the stimulus intensity of either image with a series of neutral density filters. In this study, we analyzed the retinal correspondence in esotropes with the same procedure. 27 esotropes were examined. 11 cases had normal correspondence and 16 cases anomalous correspondence in PDH. All of the 11 normal correspondence cases retained normal correspondence when we reduced the stimulus intensity of either image of fixating eyes or squinting eyes. In the 16 anomalous correspondence cases in PDH, 2 cases showed normal correspondence when the stimulus intensity of the fixating eyes was reduced. On the other hand, 3 cases showed normal correspondence when the stimulus intensity of the squinting eyes was reduced. In fixed heterotropia, both the fovea and the part of the retina of the squinting eye which received the same images as the fovea of the fixating eye (fixating point), were suppressed by the fixating eye. We consider that, in some cases with anomalous retinal correspondence in PDH, when the stimulus intensity of the fixating eyes or the squinting eyes is reduced, the balance of the sensitivity of the foveas and the fixating points of the squinting eyes change, and show normal correspondence. PMID- 8368189 TI - [The assessment of blue mechanism by measuring the threshold versus intensity curve under flashed background]. AB - The threshold versus intensity curve with brief blue stimuli with a flashing background of the same wavelength was measured in normal subjects and subjects with several kinds of optic nerve and retinal diseases. In young normal subjects the threshold curve rose sharply away from the line measured under the same conditions but without flashing blue background, as has been reported in measurements with light of long wavelengths. In the convalescent stage of optic neuritis, diabetic retinopathy, and central serous chorioretinopathy, the threshold curves presented two patterns; one pattern was shifted upward and the other shifted upward and to the right. We suggest that this method with short wavelength light is useful in differentiating retinal diseases from the change of optic media, and for layer-by-layer diagnosis of retinal diseases. PMID- 8368190 TI - [The influence of target blurring and simulated opacity of the ocular media on automated perimetric thresholds]. AB - The influence of target blurring and simulated opacity of the ocular media on the sensitivity of the central visual field in quantitative static perimetry was studied using a SARGON program of the automated perimeter Octopus 201. Ten eyes of 10 normal subjects aged from 21 to 35 were examined with target sizes 1, 3, and 5; 4 spherical plus lenses of +1.0D, +2.0D, +3.0D, and +5.0D; 5 kinds of occlusion diffusers which corresponded to the visual acuities of 1.0, 0.8, 0.6, 0.4, and 0.1; and 4 neutral density filters of 0.1, 0.3, 0.6, and 1.0 log units. The studies suggested that there was little difference between the sensitivity for target size 1 and that for target size 3 in spite of slight blurring of the target and simulated opacity of the ocular media. We concluded that target size 1 was as useful as target size 3 in quantitative static perimetry. PMID- 8368191 TI - Early journals in hypnosis: an update. AB - To date, 139 journals concerned primarily with hypnosis have been identified. This article lists another 20 periodicals, including the first American journal, the Magnet, which was briefly published in 1835 in Hanover, New Hampshire. PMID- 8368192 TI - Hypnotic susceptibility, mood state, and cardiovascular reactivity. AB - In this study we explored the relationship between hypnotic susceptibility measured with the Harvard Group Scale of Hypnotic Susceptibility (HGSHS) and cardiovascular parameters. After assessing their degree of hypnotic susceptibility, we induced 21 female students into happy mood states and into sad mood states. During the mood state induction we monitored blood pressure, heart rate, and cardiac vagal tone continuously. The study demonstrated a strong relationship between hypnotic susceptibility and both cardiac vagal tone and heart rate reactivity. Subjects with lower heart rate and greater vagal tone during baseline and greater heart rate increases during mood induction were more susceptible to hypnosis. Multiple regression analyses indicated that approximately 40% of the individual difference variance of hypnotic susceptibility was accounted for by baseline cardiac vagal tone and heart rate reactivity during mood state. The data demonstrate that autonomic tone, assessed by cardiac vagal tone and heart rate reactivity, are related to hypnotic susceptibility as measured by the HGSHS. PMID- 8368193 TI - The effect of preventive measures in reducing aftereffects to hypnosis. AB - In the present study we assessed the efficacy of several procedures in minimizing the occurrence of aftereffects of a hypnotic induction. We gave experimental subjects (n = 347) a brief lecture dispelling some myths about hypnosis, told them no psychological treatment would be undertaken, and then administered the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) in which all references to aftereffects had been removed. We gave the standard version of the HGSHS:A to control subjects (n = 340). Although the treatment condition did not reduce the overall incidence of effects, long-term effects were significantly reduced. Medical and psychosocial histories were obtained from subjects prior to the induction, but they proved to be of limited value in predicting sequelae. Contrary to the results of Coe & Ryken (1979), hypnosis produced more frequent sequelae than a nonhypnotic classroom experience (watching a film followed by an introductory psychology lecture) for subjects in an ad hoc control group. PMID- 8368194 TI - Satanic agency and mesmerism reviewed--James Braid. AB - Satanic Agency and Mesmerism Reviewed, In A Letter To The Reverend H. Mc. Neile of Liverpool, is a 12-page book in which James Braid laid the foundation stone of medical hypnotism. The present copy of this book is said to be unique. No other copy of this book has been found in the United States or England. The book, which is in the Rare Book Collection at the Wichita State University Ablah Library, came from the library of Albert Moll. The age of mesmerism or animal magnetism was brought to a close by James Braid, and in this book, his first work on mesmerism. Braid used the word hypnotism to replace mesmerism. His first use of the word occurred in this work and not, as is generally believed, in his later work, Neurypnology. PMID- 8368195 TI - Risk management in hypnotic recall of near-death experiences. AB - A substantial number of people facing physical and/or psychological crisis report having a near-death experience (NDE) involving a subjectively real experience of an alternate reality. Where NDE content is associated with positive emotions, benefit might be gained by hypnotic recall of the NDE, yet such recall might involve possible risk in the form of reactivation of the original crisis. In this article we describe a study involving hypnotic recall of positive NDEs by one male and five female subjects. We describe in detail some procedures to minimize risk, including a hypnosis protocol. PMID- 8368196 TI - Resistance to health: when the mind interferes with the desire to become well. AB - Secondary gain has long been viewed as a variable that can significantly affect a patient's recovery from such conditions as chronic pain disorders, factitious and somatoform disorders, and other psychological disorders. Secondary gain has not been evaluated in terms of its impact on major illnesses such as cancer or autoimmune disorders. In this paper I discuss how secondary gain can be present in such illnesses and how it results in a resistance to health. This resistance to health can lead not only to medical noncompliance, but can also ultimately affect the progression and recovery from the illness. I describe how hypnosis can be used to ferret out this resistance to health and how patients in a hypnotic state will indicate or express their resistance to becoming healthy. The advantage of this approach is that it enables the clinician to deal directly with the patient's unconscious resistance to health. PMID- 8368197 TI - Etienne Felix d'Henin de Cuvillers: a founder of hypnosis. AB - Etienne Felix d'Henin de Cuvillers (1755-1841) was one of the few followers of Mesmer who continued to study, practice, and refine animal magnetism after its eclipse resulting from the 1784 publication of the essentially negative investigatory reports of the French commissions. He differed from Mesmer in that he denied the existence of a magnetic fluid, emphasized the role of mental processes in mesmerism and in general behavior, and anticipated the much later psychodynamic constructs of transference and countertransference. In addition, he used and publicized a system of scientific nomenclature based upon the "hypn-" prefix for which Braid has usually, but inaccurately, been given credit for originating. PMID- 8368198 TI - Foreword: health care reform in the United States--the Presidential Task Force. PMID- 8368199 TI - Regulation and federalism: legal impediments to state health care reform. AB - In recent years, many states have attempted to address the cost and access problems that face their health care systems. Such efforts, however, are significantly impeded by a variety of federalism doctrines that limit the ability of states to regulate the health care market. This Article surveys some of those federalism barriers, including the constitutional restraints imposed by the Commerce Clause, the Privileges and Immunities Clause, and the Fourteenth Amendment, and the statutory hurdles created by ERISA, the Social Security Act, and the Americans with Disabilities Act of 1990. This Article concludes that the restraints that these doctrines and statutes place on states reflect not only federalism concerns, but also deeper ambivalence about governmental regulation of the health care market. Only when that ambivalence is resolved can a proper division of labor between the states and federal government be determined. PMID- 8368200 TI - Community care, competition and coercion: a legal perspective on privatized mental health care. AB - Even as the Clinton administration considers an increased federal commitment to mental health care, delivery of such care remains fixed at the state level. In Massachusetts, state officials are privatizing mental health care on an unprecedented scale, an experiment that promises to provide better care at lower cost. This Note explores whether privatization can achieve that lofty goal, given a legal system that has made individual patient autonomy its preeminent value. The author concludes that wide-scale privatization and modern notions of self determination can only coexist with a significant investment in the support services that are critical to the community tenure of former state hospital patients. PMID- 8368201 TI - Reforming the health care system: the universal dilemma. AB - This Article surveys alternative approaches by which the advanced industrialized nations seek to cope with the twin problems that health care poses everywhere: the provision of universal access to health care and the control of national spending on health care. Although approaches to these twin problems vary considerably among nations at this time, there may well be a convergence toward a common approach in the next century. Under that approach, all health care systems will be subject to top-down global budgets and will put their health care providers into "statistical fishbowls" that reveal just how effectively these providers allocate the global budgets at their disposal. PMID- 8368202 TI - An ethical perspective on health care insurance reform. AB - Much recent analysis of health care insurance reform emphasizes economic and policy issues. In contrast, this Article examines health policy issues from the viewpoint of medical ethics. The critical ethical "problem" in health care today is that ability to pay determines the availability and quality of care. This Article discusses three types of proposed solutions: health care insurance reform, health care financing reform, and health care cost reform. It sketches an ethical framework for evaluating health policy and presents seven specific propositions that an ethical analysis of health care reform proposals raises. This Article concludes that remedying the unethical treatment of certain classes of patients requires both health care financing reform and health care cost reform; health care insurance reform will not suffice. PMID- 8368203 TI - Canadian Medicare: can it work in the United States? Will it survive in Canada? AB - Any discussion of health care reform in the United States inevitably draws comparisons from the Canadian model. This Article frames the debate over the merits of the Canadian system by introducing its basic features, exploring its advantages, and discussing its limitations. In evaluating the prospects for a Canadian-type system in the United States, the author focuses on the need to rethink--as Canada has--the viability of market-based approaches to health care. PMID- 8368204 TI - Selling cost containment. AB - Health care expenditures in the United States have continued to grow despite efforts to control them. This Article discusses the need for health care reform, outlines the model that reform should follow, and considers why the United States has not progressed toward a workable solution. It introduces a single-payer approach to cost containment and explains how such an approach could be "sold" in the United States. Finally, the Article examines various ways to mobilize support for such health care reform. PMID- 8368205 TI - Projects study pharmaceutical care outcomes in ambulatory patients. PMID- 8368206 TI - Technician status, therapeutic interchange are subjects of resolutions by National Association of Boards of Pharmacy. PMID- 8368207 TI - Filtration of ampul contents. PMID- 8368208 TI - Career ladder for pharmacy interns. PMID- 8368209 TI - Protecting yourself from antimicrobial exposure. PMID- 8368210 TI - Cocaine hydrochloride topical solution prepared for ophthalmic use. PMID- 8368211 TI - Needleless i.v. administration systems. PMID- 8368212 TI - Pharmacists must receive all incident reports involving medications. PMID- 8368213 TI - Value of investigational drugs. PMID- 8368214 TI - X-rays and i.v. pump performance. PMID- 8368215 TI - Pharmacist deployment in support of Operation Restore Hope. PMID- 8368217 TI - Tap water should not be used. PMID- 8368216 TI - Community service at Utah. PMID- 8368218 TI - Pharmaceutical care and professional maturation. PMID- 8368219 TI - Computerized relational database for monitoring clozapine therapy. AB - The use of a computerized relational database to satisfy the patient-monitoring requirements of clozapine's manufacturer at an Oregon state psychiatric facility is described. The pharmacy department designed a computerized system to efficiently manage the patient-monitoring requirements of clozapine's manufacturer. A relational database program allows information in database files to be readily retrieved and organized into standardized or customized reports. These reports provide white blood cell (WBC) counts to the drug's manufacturer, patient discharge information to other clozapine providers, psychiatric test results to treating physicians, financial data to hospital administration, and other key data related to the facility's clozapine treatment system. The computerized system minimized the additional workload required to dispense clozapine, decreased the cost of clozapine by $234,441 compared with the cost under the closed distribution system, and provided for comprehensive clinical monitoring. Between May 1991 and October 1992, 168 clozapine recipients were monitored; pharmacists notified physicians about 86 patients not meeting WBC count criteria. The use of a computerized relational database enabled a state psychiatric hospital to efficiently manage the burden of monitoring clozapine recipients. PMID- 8368220 TI - Use of clozapine in Texas state mental health facilities. AB - Clozapine-use patterns in facilities operated by the Texas Department of Mental Health and Mental Retardation are reported. Data collected by manual and automated tracking systems from January 1990 through July 1992 were analyzed to determine patient demographics, the number of patients started on clozapine and the number who stopped taking the drug, the reasons for discontinuation, and other variables. Of 852 clozapine recipients still in the departmental system by the end of the study period, 134 (16%) had discontinued the drug by that date. There were no significant differences in gender, age, or race between the patients who discontinued the therapy and those who did not. Almost one fourth of the patients who discontinued clozapine therapy did so within the first month, and more than 90% did so within the first year. The most common reasons for discontinuing the medication were lack of clinical response, patient refusal or request, and adverse effects, including agranulocytosis. More women than men discontinued the drug because of adverse effects. Although relatively few patients discontinued clozapine during the study period, many had only recently begun taking the drug, and some of these may discontinue it in the near future. Of 852 clozapine-treated patients served by the Texas Department of Mental Health and Mental Retardation between January 1990 and July 1992, 16% discontinued the therapy. One fourth of these did so within the first month of treatment. PMID- 8368221 TI - Adding an expensive drug to the formulary. PMID- 8368222 TI - Eosinophilic meningitis. PMID- 8368223 TI - Eosinophilic pleocytosis in coccidioidal meningitis: frequency and significance. AB - PURPOSE: Coccidioidal meningitis (CM) is a major source of morbidity and mortality in endemic regions. The diagnosis of CM is a clinical challenge. Eosinophilic pleocytosis (EP) is an uncommon finding and present in a relatively limited number of conditions. In order to determine the frequency and the prognostic significance of EP in CM, we conducted the present study. PATIENTS AND METHODS: Retrospective chart review of all patients diagnosed as having CM between 1986 and 1991 at Kern Medical Center. All patients had clinical and cerebrospinal fluid (CSF) findings confirmatory of CM. RESULTS: Nineteen patients (70%) in the study group had EP, and of these, 8 patients (30%) met the criteria for eosinophilic meningitis (greater than or equal to 10 eosinophils/mm3). No correlation was found between EP and age, sex, race, results of complement fixation test for coccidioidal antigen in CSF or serum, peripheral eosinophilia, or outcome. CONCLUSION: The presence of EP is a frequent observation in CM. Although we did not demonstrate any prognostic correlation with EP, this finding is of major diagnostic significance and its presence should bring attention to the diagnosis of CM. PMID- 8368224 TI - Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone. AB - PURPOSE: To assess the status of the hypothalamic-pituitary-adrenal (HPA) axis in cortico-steroid-treated patients whose prednisone dose had been tapered to physiologic doses. PATIENTS AND METHODS: The design of the study was a retrospective chart review of 50 consecutive patients receiving 10 mg or less of prednisone daily at a university teaching hospital rheumatology clinic. Patients were given a rapid adrenocorticotropic hormone stimulation test, with cortisol levels obtained at baseline and after intravenous administration of cosyntropin. Charts were reviewed for duration of therapy, highest, current, and total cumulative steroid dose, and average daily steroid dose in each month of the preceding 2 years. RESULTS: Current steroid dose was the only significant indicator of HPA axis function. Patients receiving less than 5 mg of prednisone daily had a normal HPA axis response, whereas those receiving 5 mg or more had widely varied responses. Neither the total, the highest prednisone dose, nor the duration of therapy was a significant indicator of HPA axis recovery. CONCLUSIONS: Spontaneous recovery of the HPA axis is usual for patients who are taking prednisone at daily doses of 5 mg or less. Return of normal HPA axis function can be achieved without alternate-day therapy in patients whose disease allows tapering to daily prednisone doses of 5 mg or less. PMID- 8368225 TI - Determinants of near fatality in acute severe asthma. AB - PURPOSE: The data extrapolated from cases of acute severe asthma that narrowly miss being fatal may prove valuable in the identification of the factors implicated in mortality. The purpose of this study was, therefore, to identify determinants of near fatality in patients with acute severe asthma. PATIENTS AND METHODS: We studied 81 patients with acute severe asthma in whom mechanical ventilation was required. Near fatality was defined as the occurrence of respiratory arrest and/or coma necessitating emergency tracheal intubation and resuscitation. In the cases that were not regarded as near fatal, tracheal intubation was performed electively because of deteriorating arterial blood gas values and/or the anticipation of exhaustion. Various continuous and categorical variables were compared in these two groups of patients. Patients with a hyperacute attack (period from onset of attack to mechanical ventilation less than 3 hours) were specifically sought and studied to determine the impact of such a course on near fatality. RESULTS: The "attack duration" (period from onset of attack to mechanical ventilation) was an important determinant of near fatality and of the subsequent clinical course. It was shorter in the group with a near-fatal episode (p < 0.03), and hyperacute attacks were uniformly near fatal. The attack duration correlated positively with the duration of the requirement for mechanical ventilation (p < 0.01). A longer attack duration was associated with an increased likelihood of the occurrence of major atelectasis (p < 0.01). There was no evidence of a relationship between near fatality and the side effects of bronchodilators as regards hypokalemia, arrhythmias, or cardiotoxicity. There was evidence of considerable under-treatment in the patient population as a whole, particularly in regard to the use of corticosteroids. CONCLUSIONS: A short attack duration is associated with an increased risk of near fatality in acute severe asthma. This is particularly evident in hyperacute attacks. Hyperacute attacks resolve rapidly once bronchodilator therapy has been instituted, suggesting that smooth muscle spasm is the predominant pathogenetic mechanism. The importance of routine anti-inflammatory therapy in mild to moderate asthma requires re-emphasis but, in addition, all patients should be provided with, and educated in the use of, bronchodilator rescue therapy, which should be available at all times. Despite current trends, the use of regular, prophylactic bronchodilator therapy in strict conjunction with anti-inflammatory agents may still be indicated. There is little evidence in the present data obtained from near-fatal cases to support the concept that cardiotoxicity related to bronchodilators contributes significantly to mortality from asthma. PMID- 8368227 TI - Single-dose intravenous therapy with pamidronate for the treatment of hypercalcemia of malignancy: comparison of 30-, 60-, and 90-mg dosages. AB - PURPOSE: To determine the efficacy, dose-response relationship, and safety of 30, 60, and 90 mg of a single intravenous dose of an aminobisphosphonate, pamidronate (APD), for the treatment of moderate to severe hypercalcemia of malignancy. PATIENTS AND METHODS: Patients with histologically proven cancer and a corrected serum calcium level of at least 12.0 mg/dL after 48 hours of normal saline hydration were enrolled in a double-blind, multicenter, randomized clinical trial. Pamidronate in 30-, 60-, or 90-mg doses was administered as a single 24 hour infusion. Serum calcium corrected for albumin, urine hydroxyproline, and calcium excretion, and serum parathyroid hormone (PTH) (1-84) were determined before and after pamidronate therapy. RESULTS: Thirty-two men and 18 women entered the study. A dose-response relationship for normalization of corrected serum calcium was seen after pamidronate administration. Corrected serum calcium normalized in 40% of patients who received 30 mg, in 61% of patients who received 60 mg, and in 100% of patients who received 90 mg of pamidronate. The decline in the serum calcium level was associated with decreased osteoclastic skeletal resorption evidenced by a decrease in urine calcium and hydroxyproline excretion. Among those with a normalized corrected serum calcium level, the mean (median) duration of normalization of the corrected serum calcium value was 9.2 (4), 13.3 (5), and 10.8 (6) days in the 30-, 60-, and 90-mg treatment groups, respectively. The response of hypercalcemia to pamidronate was not significantly influenced by the presence of skeletal metastases. PTH 1-84, suppressed in patients on entry into this study, increased to a greater extent in those patients with osteolytic skeletal metastases compared with those with humoral hypercalcemia of malignancy. Clinical improvement, including improved mental status and decreased anorexia, accompanied the decline in the corrected serum calcium level in all three treatment groups. Side effects included low-grade fever, asymptomatic hypocalcemia, hypomagnesemia, and hypophosphatemia. CONCLUSIONS: A single-dose infusion of 60 to 90 mg of pamidronate was highly effective and well tolerated and normalized corrected serum calcium in nearly all patients (61% to 100%) with hypercalcemia of malignancy. PMID- 8368226 TI - Arterial underfilling does not cause sodium retention in cirrhosis. AB - PURPOSE: To test the peripheral arterial vasodilation hypothesis of sodium retention in cirrhosis. This states that sodium retention is triggered by arterial underfilling and predicts that development of sodium retention will be associated with significant and related declines in indices of arterial filling that reverse when sodium retention resolves. DESIGN: Longitudinal evaluation of a cohort of patients with alcoholic liver disease. PATIENTS AND METHODS: Eighteen men, 8 of whom were studied twice, 3 three times, 2 four times, and 5 five times (40 between-study comparisons). Between 23 studies, the patients were ascites free (Group NN). Ascites spontaneously disappeared between seven studies (Group YN), appeared between six studies (Group NY), and remained present between four studies (Group YY). Between-study changes in blood volume, arterial blood pressure, cardiac output, systemic vascular resistance, left atrial volume, left ventricular diastolic diameter, aortic root diameter, aortic blood velocity, plasma norepinephrine and atrial natriuretic factor concentrations, plasma renin activity, and urinary sodium excretion were evaluated by paired t-tests. These changes were also compared among groups by analysis of variance. In addition, correlations among the changes were sought. RESULTS: Systolic, diastolic, and mean arterial pressures, left ventricular diastolic diameter, aortic root diameter, stroke volume, cardiac output, plasma norepinephrine concentration, and systemic vascular resistance were unchanged between studies. Left atrial volume increased between studies in Group NY. Pulse pressure fell more in Group NY than in Groups NN and YN, principally as a result of a decline in systolic blood pressure. Plasma norepinephrine concentration, plasma renin activity, and blood volume rose more in Group NY than in Groups NN, YN, and YY. Changes in both systolic and pulse pressures were directly correlated with the change in sodium excretion but unrelated to the change in plasma norepinephrine concentration. Changes in plasma norepinephrine concentration and plasma renin activity were unrelated to changes in blood pressure, systemic vascular resistance, and urinary sodium excretion. CONCLUSIONS: None of the indices of arterial filling tested except pulse pressure were related to sodium retention. Reduced pulse pressure is inconsistent with arterial underfilling, as peripheral vasodilation instead increases pulse pressure by increasing diastolic run-off. These data do not support the hypothesis that arterial underfilling is the stimulus for sodium retention in alcoholic cirrhosis. PMID- 8368228 TI - Abdominal wall fat index, estimated by ultrasonography, for assessment of the ratio of visceral fat to subcutaneous fat in the abdomen. AB - PURPOSE: To establish a new index of regional fat distribution using ultrasonography for assessment of the ratio of the visceral fat area (V) to the subcutaneous fat area (S) (V/S ratio). SUBJECTS AND METHODS: The subjects examined were 62 patients (23 males and 39 females); 51 patients had hyperlipidemia and 11 patients had glucose intolerance. The mean body mass indices ranged from 20.3 to 42.9. The mean age of the patients was 44 +/- 13 years. The thicknesses of the preperitoneal fat layer (P) and subcutaneous fat layer (S) in the abdomen were measured by ultrasonography and the P/S ratio was calculated. The V/S ratio was obtained with radiographic computed tomography. RESULTS: Of the various P/S ratios examined, the ratio of the maximum thickness of preperitoneal fat to the minimum thickness of subcutaneous fat was most closely correlated with the V/S ratio (r = 0.746, p < 0.0001). This ratio was termed the abdominal wall fat index (AFI). AFI was positively correlated with serum triglyceride levels and negatively correlated with high-density lipoprotein cholesterol (r = -0.312, p < 0.05), whereas the V/S ratio was correlated with triglyceride levels. AFI was positively correlated with basal insulin levels in both men and women. CONCLUSION: These results suggest that AFI measured by ultrasonography may be a new indicator of visceral fat deposition, and may reflect metabolic disorders such as lipid metabolism and glucose metabolism disorders. PMID- 8368229 TI - Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. AB - OBJECTIVE: To review (1) the clinical epidemiology of bleeding during anticoagulant therapy with heparin or warfarin, (2) data useful in estimating the risk for bleeding in individual patients, and (3) the efficacy of methods for its prevention. METHODS: Relevant literature was identified by a computerized search of the Medline database and by review of the bibliographies of original and review articles. Studies were classified according to their design. Estimates of the risk for bleeding during anticoagulant therapy, compared with the risk without therapy, were obtained from randomized trials. Estimates of the frequency of bleeding during the course of anticoagulant therapy and information about risk factors for bleeding were obtained primarily from longitudinal studies of inception cohorts of patients followed from the start of therapy. MAIN RESULTS: The average daily frequencies of fatal, major, and major or minor bleeding during heparin therapy were 0.05%, 0.8%, and 2.0%, respectively; these frequencies are approximately twice those expected without heparin therapy. The average annual frequencies of fatal, major, and major or minor bleeding during warfarin therapy were 0.6%, 3.0%, and 9.6%, respectively; these frequencies are approximately five times those expected without warfarin therapy. The risk for anticoagulant-related bleeding is highest at the start of therapy: during warfarin therapy, the risk for major bleeding during the first month of therapy is approximately 10 times the risk after the first year of therapy. An individual patient's risk for major anticoagulant-related bleeding can be estimated on the basis of specific risk factors such as the intensity of the anticoagulant effect achieved and the presence of serious comorbid diseases, especially cerebrovascular, kidney, heart, and liver disease; older age and concurrent medicines may also be independent risk factors. Major bleeding most often affects the gastrointestinal tract, soft tissues, and urinary tract. Diagnostic evaluation of gastrointestinal bleeding and gross hematuria leads to identification of previously unknown lesions in approximately one-third of cases, even when the prothrombin time is elevated. Intracranial bleeding is rare, but it is frequently fatal. The frequency of bleeding during warfarin therapy is reduced by less intense therapy achieving a prothrombin time with an International Normalized Ratio of 2.0 to 3.0, which is efficacious for most indications. CONCLUSION: Anticoagulant-related bleeding is common and often serious. The risk for bleeding can be estimated in an individual patient, giving the primary physician a quantitative basis for weighing the risks and benefits of therapy and for optimizing patient management. The frequency of anticoagulant-related bleeding is reduced by less intense warfarin therapy. Future studies should evaluate new approaches to management that may further reduce complications while maintaining efficacy. PMID- 8368230 TI - International hero. PMID- 8368231 TI - Headaches, diabetes insipidus, and hyperprolactinemia in a woman with an enlarged pituitary gland. PMID- 8368232 TI - Sympathetic dysautonomia as a remote effect of Hodgkin's lymphoma. PMID- 8368233 TI - Exacerbation of celiac disease after cure of Cushing's disease. PMID- 8368234 TI - Acetaminophen hepatotoxicity augmented by zidovudine. PMID- 8368235 TI - Warfarin and azathioprine: a drug interaction does exist. PMID- 8368236 TI - Water loading test in the reset osmostat variant of SIADH. PMID- 8368237 TI - True telomeric translocation in a baby with the Prader-Willi phenotype. AB - We report on a baby with a nonreciprocal de novo unbalanced translocation between chromosomes 12 and 15. Her karyotype was 45,XX, -12, -15, +der(12)t(12;15)(pter- >qter::q13-->qter). The paternal origin of the 15q11-13 region was shown by DNA marker studies and, consistent with this, the baby had the Prader-Willi (PWS) phenotype. The breakpoint on 12q was distal to D12S11 (lambda MS43) which maps to 12q24.3-qter. Fluorescent in situ hybridization using the oligonucleotides (TTAGGG)7 and (AATCCC)7 showed that the 12q telomere was still present within the translocated chromosome. Thus, the translocation was within or onto the end of the telomere of 12q. This unusual translocation is further evidence of an unexplained instability of the 15q11-13 region. PMID- 8368238 TI - Mosaic tetrasomy 8p: molecular cytogenetic confirmation and measurement of glutathione reductase and tissue plasminogen activator levels. AB - We report the case of a 5-year-old girl with severe developmental disabilities, skeletal anomalies, hypotonia, rectal atresia, malrotation of the intestine, horseshoe kidney, vesicoureteric reflux, and minor facial anomalies. Conventional cytogenetic techniques suggested that she had a mosaic 46,XX/47,XX,+i(8p) constitution, and the identity of the isochromosome was confirmed by in situ hybridization and chromosome painting. Polymorphic DNA markers are consistent with the i(8p) having arisen as the result of a segregation error and centromere misdivision at the second maternal meiotic division. The i(8p) was seen in 17/25 (68%) lymphocytes at the age of one month but had declined to 31/100 (31%) cells by the age of 5 years. At this time the i(8p) was seen in 30/68 (44%) cultured skin fibroblasts. The proposita had an approximately twofold increase in red cell glutathione reductase activity but a normal level of tissue-plasminogen activator. These enzyme results are consistent with the known localisation of the glutathione reductase gene on the short arm of chromosome 8 but suggest that the tissue-plasminogen activator gene may map outside this region. PMID- 8368239 TI - Multiple pterygium syndrome with body asymmetry. AB - We report on a fetus with multiple pterygia in the popliteal, antecubital, intercrural, axillary, and nuchal region, arthrogryposis, camptodactyly, anal atresia, hypospadias, ambiguous genitalia, and neonatal death. Arthrogryposis was much more pronounced at the left than at the right side. Moreover, there was gross body asymmetry with hypoplasia of the left arm, leg, pelvis, and kidney. As this spectrum of anomalies does not fit any of the known multiple pterygium syndromes, this patient adds another clinical entity to the already wide spectrum of multiple pterygium syndromes. PMID- 8368240 TI - VACTERL with hydrocephalus: spontaneous chromosome breakage and rearrangement in a family showing apparent sex-linked recessive inheritance. AB - The rate of spontaneous and mitomycin C induced chromosome breakage and sister chromatid exchange (SCE) was studied in three related cases diagnosed with VACTERL-H syndrome. There have been recent reports of sporadic patients with VACTERL-H in whom high rates of chromosome breakage were observed. This has led to the suggestion that some of these patients may represent the severe expression of Fanconi anemia. The pattern of inheritance in our family is highly suggestive of X-linked recessive inheritance supporting the hypothesis that VACTERL-H is, at least in some cases, a syndrome and not an association. PMID- 8368241 TI - Second family with "apple peel" syndrome affecting four siblings: autosomal recessive inheritance confirmed. PMID- 8368242 TI - Prenatal diagnosis of nail-patella syndrome by intrauterine kidney biopsy. PMID- 8368243 TI - Peters' plus syndrome. PMID- 8368244 TI - Waardenburg syndrome and meningomyelocele. PMID- 8368245 TI - The joining circles. PMID- 8368246 TI - Hypertrichosis, atrophic skin, ectropion, and macrostomia (Barber-Say syndrome): report of a new case. AB - We report on a child, born to a consanguineous parents, who presented with a multiple congenital anomalies (MCA) pattern consisting of severe hypertrichosis, macrostomia, ectropion, and atrophic skin. To our knowledge this is the third case with this combination of defects. The two previous cases were reported by Barber et al. [Syndrome Identification VIII(1):6-9, 1982], and David et al. [Am J Med Genet 41:192-195, 1991]. PMID- 8368247 TI - Further delineation of the epidermal nevus syndrome: two cases with new findings and literature review. AB - "Epidermal nevus syndrome" ("ENS") is a neurocutaneous disorder in which epidermal nevi are associated with other abnormalities, most commonly of the skeletal and central nervous systems. We present two cases of epidermal nevus syndrome (ENS) with very different clinical findings. The first case is a newborn with multiple linear epidermal nevi of the trunk and limbs, and several other anomalies, including bony duplications of the lower limbs and hypoplastic left heart syndrome. The second patient, a 6-year-old boy, has a linear nevus sebaceous of the scalp with severe CNS involvement, including generalized seizures, moderate mental retardation, microcephaly, and a left hemiparesis. He also has genitourinary, cardiac, and skeletal defects. These two patients exhibit several abnormalities not previously recognized and illustrate the wide clinical spectrum of "epidermal nevus syndrome." We present a review of the clinical findings in 74 cases of "ENS." Correlation was noted between the presence of skin lesions located on the head and CNS involvement. The wide clinical spectrum of "ENS" as illustrated by these two patients suggests that "ENS" is a causally heterogeneous group of disorders. PMID- 8368248 TI - Alpers progressive infantile neuronal poliodystrophy: an acute neonatal form with findings of the fetal akinesia syndrome. AB - We report on 8 patients from two families with Alpers syndrome. The onset in one family was prenatal and in the 4 patients who were examined, severe microcephaly, intrauterine growth retardation, and typical manifestations of fetal akinesia, including retrognathia, joint limitations, and chest deformity were found. The second family presented with an early infantile form. All the affected offspring had micrognathia and one had findings of fetal akinesia, comparable to those seen in the other family. Microcephaly was mild at birth and progressed with age. Refractory neonatal convulsions, swallowing difficulties, and pneumonia complicated the clinical course of patients in both families, and all the patients died before age 20 months. Results of comprehensive biochemical and metabolic studies in both families were normal and the diagnosis was supported by demonstration of extensive progressive brain atrophy on CT and typical histological findings. Patients without a detectable defect in energy metabolism and normal liver histology comprise a distinct subset of Alpers syndrome. Until the metabolic defect(s) is defined, we suggest naming the acute neonatal form of this subset of Alpers syndrome "type 1." PMID- 8368249 TI - Congenital muscular dystrophy with neurological abnormalities: association with Hirschsprung disease. AB - We report on a baby girl with congenital muscular dystrophy (CMD) with neurological abnormalities ("CMD Plus" condition), who also had Hirschsprung disease. This association may indicate a category of congenital muscular dystrophy with involvement of the visceral nervous system. We propose that Hirschsprung disease be added to the list of anomalies pertaining to the "CMD Plus" array, and that CMD should be considered when Hirschsprung disease occurs with central nervous system anomalies. PMID- 8368250 TI - Lack of X inactivation: loss of one X inactivation center in a case with mos45,X, 21, +der(21)t(X;21) (p21.3;p11.2)/46,X,t(X;21) (p21.3;p11.2). AB - We present a girl with a mos45,X,-21, +der(21)t(X;21) (p21.3;p11.2)/46,X,t(X;21) (p21.3;p11.2) chromosome constitution. The ratio of these cells was 59/26 in phytohemagglutinin (PHA)-stimulated lymphocytes. The 45,X,der(21)t(Xp-;21p+) cells lacked an X inactivation center located at Xq13 on the derivative X chromosome; in these cells, the whole normal X chromosome and the distal part of Xp translocated onto the derivative chromosome 21 were early replicating. She had moderate mental retardation and other findings different from those that occur in the Ullrich-Turner syndrome. Her phenotype may be due to the functional excess of the distal part of Xp on the derivative 21 in 45,X,der(21)t(Xp-;21p+) cells; thus, this might be another type of the "lack of X-inactivation" syndrome. PMID- 8368251 TI - Lethal multiple pterygium syndrome: report of a case with neurological anomalies. AB - We report on a 22-week female fetus with multiple pterygia, congenital joint contractures, muscle hypoplasia, cystic hygroma, hydrops, pulmonary and cardiac hypoplasia, facial anomalies, and growth retardation. Examination also documented microcephaly, brain immaturity, and severe cerebellar and pontine hypoplasia with absence of the pyramidal tracts. The spinal cord showed a marked decrease in size of all white matter tracts. The muscles were markedly hypoplastic. The relation of the neurological findings to the development of the syndrome is discussed. PMID- 8368252 TI - Cerebro-reno-digital (Meckel-like) syndrome with Dandy-Walker malformation, cystic kidneys, hepatic fibrosis, and polydactyly. AB - We report on a boy with several findings of the Meckel syndrome, such as hepatic fibrosis, polycystic kidneys, post-axial hexadactyly, and genital abnormalities, but a Dandy-Walker malformation rather an occipital meningocele. Progressive deterioration of renal function beginning at 37 months led to death at 43 months. Both Dandy-Walker malformation and survival to the fourth year are unusual findings in Meckel syndrome. This uncommon combination represents a further demonstration of the pleiotropy/heterogeneity of the cerebro-reno-digital syndromes. PMID- 8368253 TI - Congenital pulmonary lymphangiectasis with chylothorax: a heterogeneous lymphatic vessel abnormality. AB - We report on 7 perinatal autopsy cases of primary congenital pulmonary lymphangiectasis (CPL) with bilateral chylothorax. This study demonstrates that primary CPL is often complicated by chylous pleural effusions with ensuing pulmonary hypoplasia. Conversely, CPL appears to be a constant pathological finding in spontaneous congenital chylothorax. These observations indicate a common pathogenesis for both disorders. The basic defect is not an intrinsic lung abnormality, but a developmental error of the lymphatic system resulting in a pulmonary lymphatic obstruction sequence. The cause of CPL is heterogeneous. Apparently, most cases are sporadic occurrences. We report the second instance of CPL in sibs. This indicates that some cases are genetically determined with autosomal recessive inheritance. CPL may also be part of a multiple congenital anomalies (MCA) syndrome such as Noonan, Ullrich-Turner, and Down syndrome. PMID- 8368254 TI - Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. AB - Misoprostol, a synthetic analog of prostaglandin, has been widely used in Brazil as an abortifacient. Abortion is illegal in Brazil. An uncertain number of these abortion attempts are unsuccessful and the pregnancy continues. We report on 7 patients whose mothers attempted to abort using this drug in the first trimester of gestation without success. The 7 patients presented with limb defects and in 4 of them a diagnosis of Mobius sequence was made. PMID- 8368255 TI - Chorioretinal dysplasia-microcephaly-mental retardation syndrome: report of an American family. AB - Recently we evaluated an American family with the chorioretinal dysplasia microcephaly-mental retardation syndrome (CDMMS, McKusick #156590). The male-to male transmission observed for the first time in the family of this report confirms autosomal dominant inheritance. Analysis of our cases and review of the literature illustrates the variable expressivity of this disorder and demonstrates the need for careful ophthalmologic evaluations of at-risk relatives in order to provide accurate recurrence risks. PMID- 8368256 TI - Severe axial anomalies in the oculo-auriculo-vertebral (Goldenhar) complex. AB - We have studied 4 infants with oculo-auriculo-vertebral (OAV) complex or Goldenhar "syndrome" who also had severe axial anomalies, including multiple vertebral segmentation errors affecting the thoracic and the lumbar spine. One of them presented a previously unreported pattern of vertebral and rib anomalies similar to spondylocostal dysostosis. Three patients had twins, and all 4 patients had other associated non-skeletal malformations which affected the midline, i.e., cleft lip and palate, esophageal atresia with tracheoesophageal fistula, and ventricular septal defect. The broad extent of the axial anomalies, the association with midline defects and twinning, and the combination in the same patient of two distinct conditions support the concept that OAV complex is a polytopic developmental field defect arising during blastogenesis. PMID- 8368257 TI - Of monsters and prodigies: the interpretation of birth defects in the sixteenth century. AB - In the sixteenth century, a time of religious and social upheaval, naturalistic theories of generation were joined to ideas that monstrous births were divine signs. In this paper, we explore how medicine and theology were combined to explain the almost cataclysmic religious, social, and political events of the century. PMID- 8368258 TI - Interrelationships of the hemifacial microsomia-VATER, VATER, and sirenomelia phenotypes. AB - The phenotypes of hemifacial microsomia-VATER, VATER, and sirenomelia patients suggest a sequence of overlapping developmental abnormalities. The malformations of 247 hemifacial microsomia (HFM) patients with one or more anomalies in other body regions were analyzed and compared with those of 255 VATER and 101 sirenomelia patients studied in the same fashion. The HFM patients were analyzed in four subgroups delineated by the number of their concomitant VATER ascertainment abnormalities (VAA). Three or more VAA occurred in 33 HFM patients who were designated to have the HFM-VATER phenotype and while no significant alteration of the HFM phenotype was found, there were notable differences in the analyses of the 20 malformation categories studied. Analyzed in separate heart and blood vessel (BV) categories, occurrences of BV defects in HFM patients with 0-1 VAA were low (4-6%) and due to anomalies other than single umbilical arteries (SUA). The BV abnormalities increased to 20% in the HFM with two VAA, HFM-VATER, and VATER phenotypes with equal occurrences of SUA and other BV anomalies. The incidence of SUA was markedly increased (64%) in the sirenomelia. Heart defects rose from 22% to 40% with the increasing VAA in individual HFM patients but were less in VATER (29%) and sirenomelia (21%) patients and were attributed to complex, conotruncal, and other early embryonic anomalies. Unilateral agenesis of paired organs systems occurred frequently and, possibly, can be attributed to an absent blood supply. Each phenotype of the sequence also had increased VAA, rib/vertebrae hypersegmentation, and monozygotic twinning. The variation in the incidences of malformations in the three phenotypes can be attributed to their relative location in the craniocranial organogenesis sequence of normal human embryologic development. PMID- 8368260 TI - Jancar syndrome: mental retardation, spasticity, and distal transverse limbs defects. AB - We report on a child with mental retardation, spasticity, and distal transverse defects of the limbs born to healthy parents related as first cousin. This is the third child reported to be affected with the syndrome described by Jancar. We confirm the existence of the syndrome as a separate entity and raise possibility that it may be inherited as an autosomal recessive trait. PMID- 8368259 TI - Isochromosome 18q in a girl with holoprosencephaly, DiGeorge anomaly, and streak ovaries. AB - We report on the clinical and pathologic findings in a girl with isochromosome 18q (46, XX,i(18q)) who had combined manifestations of monosomy 18p and trisomy 18q. Major congenital anomalies included premaxillary agenesis, alobar holoprosenphaly, double outlet right ventricle, DiGeorge anomaly and streak ovaries. The clinical spectrum in i(18q) is very broad. PMID- 8368261 TI - Norman-Roberts syndrome: clinical and molecular studies. AB - We report on a 7-year-old boy with microcephaly, bitemporal hollowing, low sloping forehead, slightly prominent occiput, widely set eyes, broad and prominent nasal bridge, and severe postnatal growth deficiency. Hypertonia, hyperreflexia, seizures, and profound mental retardation were also present. Brain MRI documented partial agyric cortex with patchy pachygyria, colpocephaly, and hypoplasia of corpus callosum and brain stem, which is consistent with the diagnosis of lissencephaly type I grade 2. On the basis of his phenotypic appearance the patient is considered to have the Norman-Roberts syndrome. Molecular studies, performed by means of in situ hybridization and DNA probe analysis, did not demonstrate deletion in the Miller-Dieker/isolated Lissencephaly critical region on the short arm of chromosome 17. PMID- 8368262 TI - Change in K+ current of HeLa cells with progression of the cell cycle studied by patch-clamp technique. AB - The K+ channel of HeLa S3 cells in metaphase was analyzed by inside-out and whole cell patch-clamp techniques. The channel had the characteristics of strong inward rectification, small conductance (22 pS at -100 mV), and dependence on intracellular Ca2+. We investigated the cell cycle dependency of the channel, using cells synchronized by harvesting them at the mitotic stage. The cell capacitance increased gradually with increases in the cell volume toward the S phase. The inward K+ currents through the channel at fixed membrane potentials were highest in early G1 and then decreased with time to a minimum in the S phase, increasing again in the M phase. The permeabilities at fixed membrane potentials were also highest in early G1, decreased to minima in the S phase, and increased again toward the next mitosis. In contrast, mean amplitude and the open probability of the single channel at a fixed membrane potential (-60 mV) did not change significantly during the cell cycle. Therefore the capacitance increases with progression of the cell cycle, whereas the permeability decreases from early G1 to an apparent minimum in the S phase. These changes may be caused by cell cycle-dependent changes in the number of channels. PMID- 8368263 TI - Disopyramide blocks pancreatic ATP-sensitive K+ channels and enhances insulin release. AB - An antiarrhythmic agent, disopyramide, was found to enhance the insulin secretory capacity of Wistar rat pancreatic islets with a half-maximal concentration of 23.3 microM. Employing a patch-clamp technique, disopyramide was found to inhibit ATP-sensitive K+ (KATP) channel activity in rat pancreatic beta-cells in primary culture without altering the unitary conductance. Half-maximal inhibition was achieved by the addition of 3.6 microM disopyramide to the intracellular bathing solution in the inside-out mode, 11.0 microM to the extracellular bathing solution in the outside-out mode, and 87.4 microM in the cell-attached mode. The binding of [3H]glibenclamide to pancreatic islets was inhibited by unlabeled glibenclamide but not by unlabeled disopyramide. Based on these observations, it is concluded that disopyramide blocks pancreatic KATP channels via binding to a site(s) distinct from the sulfonylurea receptor. This effect may be causatively involved in disopyramide-induced hypoglycemia. PMID- 8368264 TI - Endothelin increases [Ca2+]i in M-1 mouse cortical collecting duct cells by a dual mechanism. AB - We tested the effects of endothelin-1 (ET-1) on intracellular calcium concentration ([Ca2+]i) of cultured M-1 mouse cortical collecting duct cells. [Ca2+]i was measured using fura 2 and a fluorescent imaging system. At a concentration of extracellular calcium ([Ca2+]o) of 1 mM, ET-1 (10(-12) to 10(-7) M) increased [Ca2+]i. A second application of ET-1 had no effect on Ca2+. In contrast, application of arginine vasopressin after an initial exposure to ET-1 induced a second Ca2+ response. In the absence of extracellular Ca2+ (1 mM EGTA) ET-1 also elicited a Ca2+ peak, indicating participation of Ca2+ release from intracellular stores in the initial Ca2+ peak. At [Ca2+]o of 10 mM, ET-1 also induced an intracellular Ca2+ peak but [Ca2+]i remained significantly elevated. The Ca2+ plateau phase was abolished by nickel (10 or 100 microM) and nifedipine (0.1 or 1 microM). We conclude that ET-1 mediates an increase in [Ca2+]i by Ca2+ release from intracellular stores and activation of a nickel- and nifedipine sensitive Ca2+ entry mechanism. PMID- 8368265 TI - B-cell size influences glucose-stimulated insulin secretion. AB - To determine whether the heterogeneous B-cell response to glucose is related to a different metabolic handling of this sugar, we have compared rat B-cells differing in their redox response to glucose stimulation. To this end, a population of B-cells showing increased NAD(P)H autofluorescence after a 15-min exposure to 16.7 mM glucose was sorted from a population of B-cells that, under the very same conditions, failed to show detectable changes in basal NADP(H) autofluorescence. Insulin secretion was evaluated by a reverse hemolytic plaque assay in these two populations, referred to as high and low NAD(P)H, respectively. After a 30-min stimulation by 16.7 mM glucose, both populations comprised secreting B-cells and B-cells that did not release detectable amounts of insulin. However, the percentage of secreting B-cells and total insulin output were larger (P < 0.01-0.02) in the high- (77.9 +/- 6.5% and 141.7 +/- 27.4 microns2 x 10(3)) than in the low-NAD(P)H population (58.7 +/- 6% and 92.7 +/- 20.5 microns2 x 10(3)). The high-NAD(P)H population also comprised B-cells that, on average, had a larger (P < 0.001) profile area (142.9 +/- 2.3 microns2) than the B-cells of the low-NAD(P)H population (118.6 +/- 1.5 microns2). Glucose induced insulin secretion was similar in the high- and low-NAD(P)H group when cells of similar sizes were compared and increased similarly in the two populations as a function of B-cell size. Analysis of variance revealed that insulin secretion was influenced (P < 0.005) by the size of B-cells and not by their NAD(P)H level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368266 TI - Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics. AB - To determine the significance of protein breakdown in regulating tumor growth and to better understand the antitumor mechanism of tumor necrosis factor in vivo, we measured the effects of a 6-h constant intravenous infusion of human recombinant tumor necrosis factor-alpha (rHuTNF) on tumor protein metabolism and cell cycle kinetics in rats bearing the Walker-256 carcinosarcoma. Protein metabolism was investigated with the use of [14C]leucine infusion; estimates of tumor cell cycle kinetics were obtained in vivo by use of 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis by flow cytometry. Reduction in tumor growth by rHuTNF was associated with a dose-dependent increase in tumor proteolysis but no change in tumor protein synthesis. At the cellular level, rHuTNF had a significant cytostatic effect on G2/M cells and caused a marked decrease in the fraction of cells capable of BrdUrd uptake. Release of BrdUrd, an indicator of cell death, was noted in only 7.5% of tumor cells labeled at the beginning of rHuTNF infusion. These results suggest that either tumor protein breakdown may influence cell cycle activity by regulating cytoplasmic protein mass or that tumor proteolysis may be a compensatory mechanism for limiting cytoplasmic size when cellular division is interrupted suddenly. PMID- 8368267 TI - Perinatal enhancement of cardiac myofibrillar creatine kinase activity without change in enzyme Km. AB - Myofibrillar creatine kinase (CK) serves as one microcompartment of the phosphorylcreatine shuttle by providing ATP as substrate for adenosinetriphosphatase (ATPase). During perinatal heart development, augmentations of myofibrillar ATPase and CK occur in concert with increased contractile performance. The maximal reaction velocity (Vmax) for CK doubles during development in both intact native myofibril and enzyme extracted from myofibril. The absence of alterations in ADP and creatine phosphate substrate Michaelis constants (Km), isoenzyme composition, or total number of -SH groups suggests active site function (Vmax) is influenced indirectly via a subunit domain effect on enzyme conformation. PMID- 8368268 TI - Polylysine activates smooth muscle myosin ATPase activity via induction of a 10S to 6S transition. AB - Polylysine (10-13 kDa) stimulates contraction in smooth muscle skinned fibers and activates actomyosin adenosinetriphosphatase (ATPase) activity in the absence of myosin light chain phosphorylation [P. T. Szymanski and R. J. Paul. Adv. Exp. Med. 304: 363-368, 1991; P. T. Szymanski, J. D. Strauss, G. Doerman, J. DiSalvo, and R. J. Paul. Am J. Physiol. 262 (Cell Physiol. 31): C1445-C1455, 1992]. To provide further information on the mechanism of polylysine action on contractility in smooth muscle, we investigated its effect on ATPase activity and conformation of purified gizzard myosin. We report here that polylysine directly stimulates myosin ATPase activity in a concentration-dependent manner. This stimulation could be completely abolished with the addition of heparin, a negatively charged heteropolysaccharide. Polylysine (10 microM) increases myosin ATPase activity to a level similar to that of myosin phosphorylation. Addition of 10 microM polylysine to phosphorylated myosin [with myosin light chain kinase and adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), to approximately 1.9 mol P/mol myosin], however, did not further stimulate ATPase activity. At 0.2 M KCl (the salt concentration at which myosin exists primary in the 10S form), the addition of polylysine increases myosin ATPase activity to a level comparable to that of untreated myosin in 0.3 M KCl. These changes parallel the increase in solution viscosity elicited by polylysine. These results suggest that polylysine induces a transition in myosin conformation from the 10S to the 6S form, and this was confirmed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368269 TI - Hyperosmotic stress stimulates tissue plasminogen activator expression by a PKC independent pathway. AB - Shear, stretch, and the generation of oxygen radicals stimulate increases in tissue plasminogen activator (t-PA) mRNA levels and antigen production, suggesting that environmental stress may regulate t-PA gene expression. We have examined whether t-PA production is also responsive to a hyperosmotic environment. Endothelial and HeLa cells were treated with hyperosmotic medium, and t-PA mRNA and antigen secretion were measured. Endothelial cells incubated in hyperosmotic medium showed a dose-dependent decrease in cell volume and a 1.9 +/- 0.3- and 3.7 +/- 0.9-fold increase in t-PA secretion at 425 and 485 mosmol/kgH2O, respectively. HeLa cells showed a 3.3 +/- 0.6- and 5.1 +/- 1.2-fold increase at the same osmolalities. Increased secretion began between 8 and 16 h and continued through 24 h. Cultures returned to isosmotic medium after 8 h of treatment continued to release 98.1 +/- 7% of the maximum levels of t-PA for the next 16 h, despite the reversal of other responses to hyperosmotic environment. t-PA mRNA levels also increased between 8 and 16 h to five times control levels but returned to baseline by 24 h. No change in intracellular Ca2+ concentration, inositol 1,4,5-trisphosphate, or diacylglycerol content was detected, suggesting that a different intracellular signal pathway may be involved in the response to hyperosmolar stimulus. Thus environmental stress may be a general stimulatory signal through which t-PA production can be induced. PMID- 8368270 TI - PKC-mediated redistribution of mitogen-activated protein kinase during smooth muscle cell activation. AB - Protein kinase C (PKC) translocates from the cytosol to the surface membrane at the time it mediates agonist-induced contraction of ferret vascular smooth muscle cells (R. A. Khalil and K. G. Morgan. J. Physiol. Lond. 455: 585-599, 1992). However, no direct communication between membrane-associated PKC and the contractile filaments has been identified. Mitogen-activated protein (MAP) kinase is a substrate for PKC and is also capable of phosphorylating the actin-binding protein caldesmon at sites phosphorylated during smooth muscle contraction in vivo (L. P. Adam, C. J. Gapinski, and D. R. Hathaway. FEBS Lett. 302: 223-226, 1992). In the present study, the hypothesis that PKC and MAP kinase are involved in a signal-transduction cascade leading to smooth muscle contraction was tested. Immunofluorescence and digital-imaging microscopy were used to localize the epsilon-PKC isoform and MAP kinase during phenylephrine-induced Ca(2+) independent activation of ferret aorta cells. We report that maintained phenylephrine-induced translocation of cytosolic PKC to the surface membrane is associated with transient redistribution of cytosolic MAP kinase to the surface membrane before cell contraction. Coincident with cell contraction, MAP kinase undergoes a second redistribution away from the plasmalemma and toward the vicinity of contractile filaments. Redistribution of MAP kinase is not stimulated by Ca2+ but is completely prevented by PKC inhibitors. The transient Ca(2+) independent but PKC-dependent redistribution of MAP kinase points to MAP kinase as a missing link in the signal-transduction cascade between membrane-bound PKC and smooth muscle activation. PMID- 8368272 TI - Interrelationship between cell pH and cell calcium in rat inner medullary collecting duct cells. AB - In this study we investigated the interrelationship between cell pH (pHi) and cell calcium (Cai) in cultured inner medullary collecting duct cells of the rat. Confluent monolayers were made quiescent by incubation for 24 h in Dulbecco's modified Eagle's medium supplemented with 0.1% serum before study. Changes in pHi and Cai were measured with the fluorescent probes 2',7'-bis(carboxyethyl)-5,6 carboxyfluorescein and fura 2. In nominally bicarbonate-free media containing 110 mM Na+ and 1 mM Cai, cell acidification to pH 6.70 increased Cai from 122 +/- 24 to 243 +/- 33 nM. In the absence of bath calcium, acidification increased Cai from 90 +/- 7 to 144 +/- 13 nM. An increase of pHi to 7.6 reduced Cai almost to baseline. Cell acidification increased inositol trisphosphate (IP3) production, and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, an IP3 antagonist, partially inhibited the rise in Cai. Elevation of Cai resulted in a sustained cell alkalinization from 7.32 +/- 0.02 to 7.58 +/- 0.04. When Cai was reduced, pHi fell to 7.25 +/- 0.01. We conclude that Cai and pHi participate in a feedback loop that modulates changes in each respective parameter. PMID- 8368271 TI - Mechanism of diltiazem's immunomodulatory effects after hemorrhage and resuscitation. AB - Although diltiazem improves immune responses after hemorrhage and resuscitation, its mechanism remains unknown. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mmHg, maintained at that level for 1 h, and then adequately resuscitated and treated with diltiazem (400 micrograms/kg body wt) or saline (vehicle). One hour after hemorrhage and resuscitation, splenic microvascular blood flow was determined by laser Doppler flowmetry. Splenocytes were also harvested and ATP levels and cytoplasmic free Ca2+ concentration ([Ca2+]i) were determined by 31P nuclear magnetic resonance and fluo 3 flow cytometry, respectively. Splenocyte functions were determined by measuring interleukin (IL) 1, IL-2, IL-3, IL-6, and tumor necrosis factor concentrations in concanavalin A stimulated supernatant with cytokine-specific cellular assays. Hemorrhage and resuscitation caused a significant decrease in the splenocyte's ability to release cytokines, which was correlated with significant reductions in splenocyte ATP levels and splenic microvascular blood flow as well as a significant increase in splenocyte [Ca2+]i. Diltiazem significantly decreased splenocyte [Ca2+]i while improving splenocyte ATP levels, cytokine production, and splenic microvascular blood flow. Nitroglycerin (71 micrograms/kg body wt) administration improved splenic microvascular blood flow to diltiazem-treated levels but failed to concomitantly improve splenocyte ATP levels or cytokine production. Thus diltiazem's immunoprotective effects appear to be the result of decreased Ca(2+) induced splenocyte injury. PMID- 8368273 TI - Albumin and Ricinus communis agglutinin decrease endothelial permeability via interactions with matrix. AB - We studied the effects of albumin and the lectin Ricinus communis agglutinin (RCA) on hydraulic conductivity (Lp) of bovine pulmonary microvascular endothelial cell monolayers (BPMVEC) because of the evidence that albumin and RCA can interfere with transendothelial albumin permeability (Siflinger-Birnboim, A., J. Schnitzer, H. Lum, F. Blumenstock, C. Shen, P. Del Vecchio, and A. Malik. J. Cell. Physiol. 149: 575-584, 1991). BPMVEC were seeded on microporous polycarbonate filters, and the liquid flux was measured by collecting effluent into a tubing of known inner diameter at transendothelial hydrostatic pressures (P) ranging from 5 to 20 cmH2O. Lp was calculated as the slope of the relationship of liquid flux per unit surface area (Jv) vs. P. Addition of RCA (50 micrograms/ml) or albumin (5 mg/ml) to the endothelial cell medium containing albumin-free Hanks' balanced saline solution (HBSS) decreased total Lp (expressed x 10(-6) cm.s-1 x cmH2O-1) from 17.2 +/- 3.6 during HBSS to 4.7 +/- 0.9 during albumin and 5.7 +/- 1.6 during RCA (P < 0.01 for both). The RCA effect, but not that of albumin, was prevented by the addition of D-galactose (0.1 M) (the cognate hapten monosaccharide of RCA). We determined the contribution of the extracellular matrix (ECM) in decreasing the Lp by obtaining ECM after treatment of the monolayers with 0.025 M NH4OH to detach endothelial cells from the ECM. Basal ECM Lp (expressed x 10(-6) cm.s-1 x cmH2O-1) was 57.0 +/- 15.3, and it decreased to 19.7 +/- 4.3 and 17.5 +/- 2.9 during RCA and albumin, respectively (P < 0.01 for both). In contrast, RCA and albumin did not alter the filter Lp values. Another lectin, Ulex europaeus agglutinin, and the protein immunoglobulin G had no effect on Lp values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368274 TI - Insulin uptake and processing by cultured mouse glomerular endothelial cells. AB - Endothelial cells isolated from a variety of vascular beds bind and transport insulin but exhibit relatively low insulin degrading activity. Because endothelial cells exhibit heterogeneity and since kidney is a major site of insulin degradation, we studied the processing of insulin by glomerular endothelial cells (GEC). When exposed to 2 x 10(-10) M 125I-labeled insulin, GEC associated with the hormone in a specific manner. This interaction was inhibited by insulin but not by a number of unrelated peptide hormones. Over a 90-min period, GEC degraded 42 +/- 3% of the 125I-insulin, as measured by solubility in trichloroacetic acid (TCA). Degradation was inhibited 90% by an excess of insulin or adrenocorticotropic hormone (10(-6) M) and 57% by glucagon, whereas growth hormone and calcitonin were without effect. Separation of plasma membrane bound from internalized insulin was achieved by decreasing extracellular pH. In the steady state, 43% of cell-associated insulin was membrane bound and 57% internalized. The fate of the internalized 125I-insulin was examined by incubating acid-washed cells at 37 degrees C for 60 min. Over this time 18% of the radioactivity was released as TCA insoluble- and 72% as TCA-soluble radioactivity. Release was increased by insulin (10(-6) M) but not by unrelated peptide hormones. In the presence of chloroquine, 125I-insulin release increased by one third while degradation fell. High-performance liquid chromatography revealed that GEC released both intact insulin and large intermediates and that chloroquine inhibited intermediate formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368275 TI - Transtrophoblast and microvillus membrane potential difference in mature intermediate human placental villi. AB - Single mature intermediate villi from term placentas after normal gestation and vaginal or cesarian delivery were identified microscopically and mounted in a bath for conventional micro-electrode studies. With the application of strict selection criteria, the following observations on electrical potential difference (PD) were made. 1) With the tissue bathed in Earle's medium (37 degrees C) the PD across the syncytiotrophoblast microvillus membrane with respect to the bath was not normally distributed. The median PD was -22 mV (range -12 to -60 mV, n = 200). This fell to -6 mV after prior incubation for 4 h with cyanide (3 mM) or iodoacetate (2 mM) but was not altered by short-term application of these agents or by 0.1 mM ouabain. Substituting Na+ in Earle's medium with choline had no effect on PD, but replacing Cl- with gluconate caused a depolarization of 6 mV (P < 0.002). Increasing KCl in the bath fluid revealed an apparently low microvillus membrane K+ conductance. The low microvillus membrane PD may reflect a low Na(+) K(+)-ATPase activity and/or a low membrane permeability to K+. 2) The transtrophoblast PD measured by insertion and withdrawal of the electrode was significantly different from zero [P < 0.003, median -3 mV (range 0 to -15 mV), n = 11]; and PD measured by insertion of the electrode into the villus core and beyond was -6 mV (significantly different from zero P < 0.003, range -2.5 to -10 mV, n = 6). If a similar PD were to exist in vivo, it could have a significant influence on ion transport across the placenta at term. PMID- 8368276 TI - Contraction history modulates isotonic shortening velocity in smooth muscle. AB - The effect of contraction history on the isotonic shortening velocity of canine tracheal smooth muscle was investigated. Muscles were contracted isometrically for 20 s at initial lengths of L(o) (length of maximal active force), 85% L(o), or 70% L(o) using electrical field stimulation. Muscles were then allowed to shorten isotonically under different afterloads either with or without first being subjected to a step decrease in length to 70% L(o). Instantaneous velocities were plotted against instantaneous muscle length during isotonic shortening. Regardless of protocol, the velocity at any muscle length during shortening was lower when the muscle was initially activated at a longer length. The isotonic shortening velocity decreased progressively during shortening at a nearly linear rate with respect to instantaneous muscle length under all conditions. Results suggest that a longer muscle length at the time of activation leads to the development of higher loads on the contractile element during subsequent shortening, resulting in a slower shortening velocity. This plasticity of the force-velocity relationship may result from cytostructural reorganization of the smooth muscle cells in response to contractile activation at different muscle lengths. PMID- 8368277 TI - Computer modeling of the oxygen supply and demand of cells of the avian growth cartilage. AB - We have used computer modeling studies to investigate the oxygen supply to the prehypertrophic and hypertrophic regions of avian growth plate. We measured experimentally the characteristics of the oxygen consumption of chondrocytes at different oxygen tensions. The oxygen consumption decreases at low oxygen tensions. This relation between oxygen tension and oxygen consumption serves as a protective mechanism that prevents the cells in the prehypertrophic zone from becoming anoxic in the regions farthest from the blood vessels. The results of the calculations, when combined with redox measurements of the cells in the growth plate, indicate that the metabolism of the chondrocytes is not controlled simply by the available oxygen supply. PMID- 8368278 TI - WW-781, a potent reversible inhibitor of red cell Cl- flux, binds to band 3 by a two-step mechanism. AB - WW-781 ([3-methyl-1-p-sulfophenyl-5-pyrazolone-(4)]-[1,3-dibutylbarbit uric acid] pentamethine oxonol), a fluorescent dye that has been used for measuring membrane potentials by optical methods, inhibits human red blood cell Cl- exchange, which is mediated by the membrane protein known as band 3 or capnophorin. The inhibition is slowly reversible upon removal of WW-781 from the medium, with a half time of approximately 4.7 min in 150 mM Cl- medium at 0 degrees C. The mechanism of inhibition by WW-781 involves a two-step binding reaction. WW-781 binds rapidly to band 3 to form an initial complex, which can also rapidly dissociate. Formation of this initial complex is followed by the much slower formation of a second complex (with a rate constant of approximately 1.1 min-1), probably involving a protein conformational change, through which WW-781 is more tightly bound to band 3. At low concentrations, WW-781 inhibits Cl- exchange with a stoichiometry of 1 WW-781 molecule per band 3 monomer, suggesting that under these conditions the binding of WW-781 is highly selective for the band 3 protein. PMID- 8368279 TI - Twitch-dependent SR Ca accumulation and release in rabbit ventricular myocytes. AB - Using caffeine-induced contractures (Ccaf) and thapsigargin (TG), we estimated the fraction of sarcoplasmic reticulum (SR) Ca released at one twitch and also the number of twitches required to reload a Ca-depleted SR. Similar results were obtained for twitches or intracellular Ca (Cai) transient with the fluorescent indicator, indo 1. Sustained exposure to 10 mM caffeine completely depletes the SR of Ca in < 5 s (as assessed by a second Ccaf). After such Ca depletion, four to five twitches are necessary to reload the SR to the steady-state level (with a twitch constant, tau = 1.6 twitches). We also determined the time required for complete inhibition of the SR Ca-adenosinetriphosphatase (ATPase) by TG. After SR Ca depletion, 5 microM TG was applied for different periods of time before a train of "reloading" twitches. A TG exposure period of 90 s was sufficient to completely prevent Ccaf after these reloading twitches. When SR is Ca depleted, the twitch is larger in the presence of TG, indicating that the SR Ca-ATPase can limit the ability of Ca influx to activate contraction. To assess SR Ca released at one twitch in cells with normally Ca-loaded SR, 5 microM TG was applied for 90 s to prevent SR Ca reuptake. Then one or several twitches were activated (causing SR Ca release, but with reuptake completely blocked). After the twitch (or train), a Ccaf was used to assess remaining SR Ca.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368280 TI - Effects of a Shaker K+ channel peptide and trypsin on a K+ channel in Necturus enterocytes. AB - We have previously demonstrated that a synthetic peptide composed of the first 22 amino acids from the NH2-terminus of the Shaker B K+ channel protein deactivates a voltage-dependent K+ channel present in basolateral membrane of Necturus small intestinal epithelial cells reconstituted into planar lipid bilayers (Dubinsky et al. Proc. Natl. Acad. Sci. USA 89: 1770-1774, 1992). We now demonstrate that this peptide interacts with the inner surface of the Necturus channel only when it is in the open or conducting configuration and that this interaction is hindered by tetraethylammonium ion, a well-established blocker of this and other K+ channels. We conclude that this peptide is an open-pore blocker of the Necturus K+ channel as it appears to be in the case of the Shaker B K+ channel. We further demonstrate that trypsin, which abolishes the ability of this peptide to block both the Necturus and the Shaker K+ channels and inhibits spontaneous inactivation of the Shaker K+ channel, also impairs the voltage-gate of the Necturus K+ channel. These findings, and others to be reported in a companion paper, suggest structural homologies between the "inactivation peptide" of the Shaker B K+ channel and the voltage-gate of the Necturus K+ channel. PMID- 8368282 TI - Further characterization of the Na-Ca exchange-dependent Ca compartment in rat ventricular cells. AB - A discrete subcellular Ca compartment, absolutely dependent upon Na-Ca exchange for its exchange, has been previously identified in ventricular cells from both adult rat and from neonatal rat cultures. The present study further characterizes this compartment in the adult ventricular myocyte. The compartment's exchange is significantly decreased by 20 microM 3,4-dichlorobenzamil. Its content responds significantly to variation of the extracellular Ca concentration ([Ca]o) and to reversal of the Na-Ca exchanger by reduction of extracellular Na concentration to zero. Its content decreases to 155 +/- 24 mumol/kg dry cell wt in 0.2 mM [Ca]o and increases to 623 +/- 48 mumol/kg at 6.5 mM [Ca]o, where it appears to be near saturation. The compartment is significantly reduced by 45Ca labeling in the presence of 10 mM caffeine (23%) and 1 mM ryanodine (22%). This compartment is not significantly affected by 1 microM thapsigargin. 45Ca activity is retained in the compartment when 45Ca washout is conducted without Na or Ca in the washout solution, i.e., Na-Ca exchange is not operative. Under these conditions, addition of 1 mM Cd to the washout produces a significant release of 45Ca from the compartment. The results are interpreted to indicate that the compartment in the adult cell has two components that are in equilibrium: a relatively small sarcoplasmic reticulum (SR) component and a larger "non-SR" component. This is in contrast to the compartment in the cultured cell in which the compartment is 2.6 times larger and has a larger SR component. The possibility that the non-SR component represents Ca bound to the cytoplasmic leaflet of the sarcolemma at SR junction regions is discussed. PMID- 8368281 TI - Immunoisolation of a K+ channel from basolateral membranes of Necturus enterocytes. AB - We have reported that a peptide composed of the NH2-terminal 22 amino acids of the Drosophila Shaker B K+ channel protein, which is responsible for the inactivation of this A-type channel, blocks the inner, open mouth of a voltage gated K+ channel present in the basolateral membrane of Necturus maculosa small intestinal enterocytes. We now demonstrate that antibodies to this "inactivating" peptide interact with proteins in solubilized and intact basolateral membranes from Necturus enterocytes. Asolectin vesicles reconstituted with the full complement of solubilized basolateral membrane proteins display 86Rb+ uptake that is inhibited by tetraethylammonium ion and abolished by immunoprecipitation with these antibodies. Furthermore, asolectin vesicles containing protein eluted from an antibody-affinity column display 86Rb+ uptake that is abolished by boiling. Finally, reconstitution of the immunoisolated protein into planar phospholipid bilayers disclosed a K+ channel whose single-channel properties are identical to those of the voltage-gated channel in the native basolateral membranes. Our data are consistent with the notion that a 150-kDa protein present in basolateral membranes of Necturus enterocytes possesses inwardly rectifying K+ channel activity and that this protein is antigenically similar to the type A K+ channel present in the flight muscles of Drosophila melanogaster and encoded by the Shaker B locus. PMID- 8368283 TI - Laser light-scattering system for studying cell volume regulation and membrane transport processes. AB - A simple and relatively inexpensive device utilizing laser light scattering for the study of volume regulatory behavior and membrane transport phenomena in cells cultured on or affixed to a rigid substrate is described in detail. Validation of the method is provided by study of cell types with known volume regulatory responses. The method we describe has numerous advantages over currently available techniques used to monitor cell volume changes. These advantages include 1) the ability to rapidly detect and quantify small cell volume changes on-line, 2) the ability to maintain natural cell morphology, cell surface contacts, and cell-to-cell interactions, 3) the ability to easily control solution temperature and gas and solute composition, and 4) the ability to perform multiple perturbations in a single experiment. The light-scattering system we describe can be modified to allow for simultaneous measurement of light scattering signals and fluorescence emission from intracellular ion-sensitive probes and membrane potential dyes. In addition, our method may be useful for the study of apical and basolateral membrane transport processes in epithelial monolayer cell cultures. PMID- 8368284 TI - Adult human aortic smooth muscle cells in culture produce active TGF-beta. AB - Vascular smooth muscle cells (VSMC) from adult human aortas proliferated in culture in response to fetal calf serum (FCS) with a population doubling time of 70-85 h compared with 35 +/- 5 h for VSMC derived from adult rat aortas. Medium conditioned on cultures prepared from aortas from three different donors and mixed 1:1 with fresh Dulbecco's modified Eagle's medium plus 20% FCS [human conditioned medium (HCM)] reduced the rate of proliferation of rat VSMC by 46 +/- 6% (n = 3) after 48 h compared with cells in fresh medium. HCM did not reduce the proportion (> 65%) of rat VSMC that entered DNA synthesis but delayed entry into mitosis by at least 18 h. This effect was similar to previous observations of the action of transforming growth factor-beta (TGF-beta) on rat VSMC (G. K. Owens, A. A. Geisterfer, Y. W. Yang, and A. Komoriya. J. Cell Biol. 107: 771-780, 1988). A TGF-beta assay using DNA synthesis in mink lung epithelial cells confirmed that human, but not rat, VSMC in culture secrete active TGF-beta. Addition of a neutralizing antibody to TGF-beta to human VSMC in the presence of 20% FCS decreased the population doubling time from 74 +/- 3 to 46 +/- 6 h (n = 3). These observations demonstrate that the long population doubling time of human VSMC is due to the production of active TGF-beta and to an inhibitory autocrine loop. PMID- 8368285 TI - Mechanisms of ET-1 potentiation of angiotensin II stimulation of aldosterone production. AB - Endothelin-1 (ET-1) exerts the following two types of aldosterone-stimulating actions on glomerulosa cells: ET-1-mediated direct stimulation of aldosterone secretion (per se effect) and potentiation of the aldosterone secretion to angiotensin II (ANG II; potentiation effect). The role of Ca2+ and protein kinase C (PKC) systems in these two effects was investigated. Incubations of calf cultured adrenal zona glomerulosa cells in low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil reduced the aldosterone secretion to ET-1. When cells were preincubated with ET-1 in a low-Ca2+ media or in the presence of the Ca2+ channel antagonist verapamil, washed, and incubated in media with normal Ca2+, ANG II showed potentiation of ANG II-stimulated aldosterone secretion. The PKC inhibitors H-7 and staurosporine did not decrease ET-1-stimulated aldosterone secretion, but they inhibited the potentiation effect of ET-1 on ANG II-mediated aldosterone secretion. Adrenocorticotropic hormone desensitization or prolonged phorbol ester stimulation of PKC resulting in desensitization also resulted in the abolition of the ET-1-mediated ANG II potentiation of aldosterone secretion. The PKC inhibitors did not affect ANG II-stimulated aldosterone secretion. We conclude that ET-1 exerts a direct stimulation of aldosterone secretion through a mechanism dependent on Ca2+ and potentiates ANG II-mediated aldosterone stimulation through a mechanism involving PKC. PMID- 8368286 TI - Free and conjugated catecholamines and serotonin in canine thoracic duct lymph: effects of feeding. AB - The source and fate of sulfoconjugated catecholamines present in plasma are not known. Sulfated norepinephrine has been shown to overflow together with free norepinephrine from a typical peripheral neuroeffector junction. Some released free norepinephrine is removed via the lymphatic system, but it is not known whether sulfated catecholamines are removed similarly. Serotonin, another biogenic amine, is released from the enterochromaffin cells into portal blood. The aims of the present study were to determine whether conjugated catecholamines and serotonin could be detected in thoracic duct lymph of dogs and to compare concentrations in lymph with those in samples of portal blood collected before and after the dogs were fed. A method is described for the extraction and purification of free and conjugated catecholamines and serotonin from lymph. In lymph and in plasma, there were similar concentrations of free (0.2-0.4 ng/ml) and conjugated (0.1-0.2 ng/ml) norepinephrine and of conjugated dopamine (0.2-1.0 ng/ml). The concentrations of free serotonin were much lower in lymph (0.1-0.2 ng/ml) than in portal blood (100-200 ng/ml). Small amounts of conjugated serotonin (0.1-0.4 ng/ml) were detected in lymph but were not detected in plasma. Feeding caused increases in concentration of conjugated dopamine in lymph and in plasma and small increases in the output of free norepinephrine and free and conjugated serotonin in lymph. PMID- 8368287 TI - A compartmental model of acute stimulation of aldosterone secretion in vivo by potassium and ANG II. AB - Conscious sheep with an adrenal autotransplant were used to study the relationship between acute change in K+ concentration and acute change in aldosterone secretion rate (ASR). The kinetics of K+ within the adrenal circulation were shown to be consistent with distribution within a single compartment. In contrast, change in ASR during and after KCl infusion was consistent with a two-compartment model, where ASR was a sigmoidal function of concentration of K+ (or other unidentified agent) in the second, or "effect," compartment. Prior work on the relationship between acute change in angiotensin II (ANG II) concentration and acute change in ASR was extended by investigating the interaction of K+ and ANG II in the control of ASR. The results of this study indicate that acute change in ANG II concentration may cause an inhibition of the usual response of the adrenal to acute change in K+ concentration. PMID- 8368288 TI - Ethanol inhibits insulin action on lipolysis and on insulin release in elderly men. AB - We have studied effects of ethanol on insulin's ability to suppress its own release and on its antilipolytic action in 12 healthy elderly men during euglycemic hyperinsulinemia. Insulin secretion was estimated from plasma C peptide concentrations. Lipolysis was determined with the two stable isotopes [2H5]glycerol and [1-13C]palmitate. Hyperinsulinemia (approximately 350 pM) decreased plasma C-peptide by approximately 60% (from 325 to 122 pM, P < 0.05). Ethanol (approximately 10 mM) completely prevented the fall in C-peptide concentration. Ethanol decreased the antilipolytic action of insulin by approximately 40% [with insulin alone, glycerol rate of appearance (Ra) decreased from 1.8 to 0.6 mumol.kg-1 x min-1; with insulin + ethanol, it only decreased from 1.8 to 1.1 mumol.kg-1 x min-1]. Ethanol did not affect palmitate Ra, which fell from 1.4 to 0.6 mumol.kg-1 x min-1 with insulin and from 1.4 to 0.3 mumol.kg 1 x min-1 with insulin plus ethanol. Fatty acid reesterification was not affected by insulin but tripled (from 0.6 to 1.9 mumol.kg-1 x min-1) in response to insulin plus ethanol. Our data showed that modest concentrations of ethanol suppressed the inhibitory actions of insulin on its own release and on lipolysis. The inhibition by ethanol of various insulin actions, including glucose disposal, lipolysis, and insulin release, in diverse tissues such as muscle, adipose tissue, and pancreas raises the possibility that ethanol may produce a state of generalized insulin resistance. PMID- 8368289 TI - Effect of hypophysectomy on plasma catecholamines and enkephalins in fetal sheep. AB - The aim of this study was to determine the effect of fetal hypophysectomy on the plasma concentrations of catecholamines and enkephalins in the fetal sheep between 120 and 140 days gestation under basal and hypoxic conditions. During basal conditions, there was no difference in the plasma concentrations of norepinephrine and epinephrine between intact and hypophysectomized groups. Fetal plasma norepinephrine concentrations were significantly increased during hypoxia in intact fetal sheep (7.2 +/- 2.2 pmol/ml, -15 min; 20.2 +/- 7.7 pmol/ml, 30 min) between 130 and 140 days, but after fetal hypophysectomy there was no significant norepinephrine response to hypoxia at this gestational age (4.7 +/- 1.3 pmol/ml, -15 min; 8.8 +/- 2.8 pmol/ml, 30 min). In contrast, fetal plasma epinephrine concentrations were significantly increased during hypoxia in both the intact (1.5 +/- 0.5 pmol/ml, -15 min; 3.3 +/- 1.7 pmol/ml, 30 min) and hypophysectomized groups (1.8 +/- 0.6 pmol/ml, -15 min; 6.8 +/- 4.1 pmol/ml, 30 min) between 130 and 140 days. During basal conditions, plasma concentrations of free Met-Enk were significantly less in hypophysectomized fetal sheep (170.8 +/- 34.3 pg/ml; 120-140 days) than in intact fetal sheep (305.6 +/- 47.3 pg/ml). There were no differences, however, in the fetal plasma concentrations of total Met-Enk between the intact (18.0 +/- 1.9 ng/ml) and hypophysectomized (16.9 +/- 2.6 ng/ml) groups. During hypoxia, there were no changes in the fetal plasma concentrations of either free or total Met-Enk in the intact or hypophysectomized groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368290 TI - Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. AB - Muscle mass and function are improved in the elderly during resistance exercise training. These improvements must result from alterations in the rates of muscle protein synthesis and breakdown. We determined the rate of quadriceps muscle protein synthesis using the in vivo rate of incorporation of intravenously infused [13C]leucine into mixed-muscle protein in both young (24 yr) and elderly (63-66 yr) men and women before and at the end of 2 wk of resistance exercise training. Before training, the fractional rate of muscle protein synthesis was lower in the elderly than in the young (0.030 +/- 0.003 vs. 0.049 +/- 0.004%/h; P = 0.004) but increased (P < 0.03) to a comparable rate of muscle protein synthesis in both young (0.075 +/- 0.009%/h) and elderly subjects (0.076 +/- 0.011%/h) after 2 wk of exercise. In the elderly, muscle mass, 24-h urinary 3 methylhistidine and creatinine excretion, and whole body protein breakdown rate determined during the [13C]leucine infusion were not changed after 2 wk of exercise. These findings demonstrate that, during the initial phase of a resistance exercise training program, a marked increase in quadriceps muscle protein synthesis rate occurs in elderly and young adults without an increase in the rate of whole body protein breakdown. In the elderly, this was not accompanied by an increase in urinary 3-methylhistidine excretion, an index of myofibrillar protein breakdown. PMID- 8368291 TI - Increased clearance of 1,25(OH)2D3 and tissue-specific responsiveness to 1,25(OH)2D3 in diabetic rats. AB - The kinetics of 1,25-dihydroxyvitamin D3 [1,25(OH)2-D3] and the in vivo response to 1,25(OH)2D3 (7.5, 15, and 30 ng/100 g body wt), infused or injected subcutaneously for 12-14 days, were studied in male spontaneously diabetic and control BB rats. In control rats, increasing doses of 1,25(OH)2D3 produced parallel increases in plasma 1,25(OH)2D3 and calcium, urinary calcium, duodenal CaBP9K, and renal CaBP28K. 1,25-(OH)2D3 at 30 ng/100 g markedly raised plasma osteocalcin and osteoblast/osteoid surfaces in the tibial metaphysis, but inhibited bone mineralization rate. In diabetic rats, plasma 1,25-(OH)2D3 concentrations were decreased, and the rise of plasma 1,25(OH)2D3 during 1,25(OH)2D3 infusion was blunted, but the free 1,25(OH)2D3 index remained normal or above normal. Diabetic rats had an increased metabolic clearance rate of 1,25 (OH)2D3 (0.38 +/- 0.015 vs. 0.24 +/- 0.007 ml.min-1.kg-1), with no further increase in 1,25(OH)2D3-infused diabetic rats; their relative production rate of 1,25(OH)2D3 was unchanged. The responses of plasma and urinary calcium, duodenal CaBP9K, and renal CaBP28K to infused 1,25(OH)2D3 were normal, as was duodenal calcium absorption in 1,25(OH)2D3-injected diabetic rats. However, the virtual absence of osteoblasts/osteoid in trabecular bone was unaltered in diabetic rats infused with 30 ng/100 g 1,25(OH)2D3, with only minimal increase of their low plasma osteocalcin levels. 1,25(OH)2D3 treatment therefore cannot be expected to reverse diabetic osteopenia. PMID- 8368292 TI - Direct measurement of change in muscle glycogen concentration after a mixed meal in normal subjects. AB - Postprandial storage of carbohydrate as glycogen in muscle was quantitated in normal subjects (n = 8) by natural abundance 13C-nuclear magnetic resonance spectroscopy with proton decoupling in a 4.7-tesla magnet. After an overnight fast three basal measurements of gastrocnemius muscle glycogen were made and a mixed meal was given. Muscle glycogen concentration rose from 83.3 +/- 5.2 to a maximum of 100.2 +/- 6.7 mmol/l muscle at 4.9 h (P < 0.01) and fell thereafter to 90.6 +/- 5.9 mmol/l muscle at 7 h postprandially (P < 0.006). The meal brought about an increase in plasma glucose from 5.4 +/- 0.2 to 7.3 +/- 0.4 mmol/l at 30 min but this was followed by a rapid fall to 6.2 +/- 0.4 mmol/l at 75 min. Plasma insulin rose from 62.4 +/- 11.4 to 900 +/- 216 pmol/l at 30 min and declined steadily thereafter. It was calculated from total muscle mass measurements and estimation of carbohydrate absorption rates that at peak muscle glycogen concentrations between 26 and 35% of the absorbed carbohydrate was stored as muscle glycogen. These data quantitate the role of skeletal muscle glycogen synthesis in postprandial carbohydrate storage and demonstrate that this tissue acts as a dynamic buffer to maintain glucose homeostasis during postprandial substrate storage. PMID- 8368293 TI - Ontogeny of GH mRNA and GH secretion in male and female rats: regulation by GH releasing hormone. AB - Growth hormone-releasing hormone (GHRH) has been shown in vitro to increase proliferation of pituitary somatotrophs, to increase transcription of the GH gene, to promote accumulation of GH mRNA, and to stimulate GH release. The in vivo involvement of hypothalamic GHRH in regulating GH mRNA content had never been clearly documented. We studied pituitary GH mRNA and GH contents and serum concentrations of GH and insulin-like growth factor I (IGF-I) in rats of both sexes during pubertal growth spurt and investigated the effects of GHRH deficiency (brought about by neonatal administration of monosodium glutamate, MSG) and exogenous GHRH administration on these parameters. In both sexes, GH mRNA content increased three- to fourfold between 4 and 12 wk of life and declined thereafter toward 33 wk of life. This was accompanied by virtually parallel changes in pituitary GH content and in serum IGF-I. Neonatal MSG abolished the pubertal increases in GH mRNA, pituitary GH, and serum IGF-I and severely impaired growth rate. Exogenous GHRH (25 micrograms/kg sc every 8 h for 7 days) given to intact animals between 6 and 7 wk of life significantly augmented pituitary GH mRNA content but was less effective in MSG-treated rats. We conclude that 1) pubertal growth spurt in both sexes is associated with rising pituitary GH mRNA content; 2) GHRH deficiency abolishes the puberty-associated increase in GH synthesis and secretion and attenuates somatic growth rate; and 3) exogenous GHRH augments GH mRNA content. Thus puberty-associated augmentation of GHRH secretion is an important mechanism of somatic growth. PMID- 8368294 TI - Regulation of brown adipose tissue lipogenesis by thyroid hormone and the sympathetic nervous system. AB - Thyroid hormone regulates lipogenesis differently in rat liver and brown adipose tissue (BAT). In the hypothyroid state, lipogenesis is suppressed in liver but enhanced in BAT. Here we investigated the mechanisms underlying increased lipogenesis in hypothyroid BAT. Housing the animals at 28 degrees C decreased lipogenesis in hypothyroid BAT to euthyroid levels. Denervation resulted in a 90% reduction in lipogenesis in hypothyroid BAT such that levels were lower than in euthyroid tissue. Thyroid hormone treatment of hypothyroid rats stimulated fatty acid synthesis in denervated BAT, as in liver, but decreased it in intact BAT. Steady-state levels of mRNA encoding acetyl-CoA carboxylase, fatty-acid synthase, and spor 14 were measured in similar animals by Northern analysis. The expression of these mRNAs mirrored the lipogenic data, showing that both thyroid hormone and the sympathetic nervous system work at a pretranslational level in this tissue. These data suggest that the increased BAT lipogenesis found with hypothyroidism is mediated by the sympathetic nervous system to counter the reduction in metabolic rate in these animals. PMID- 8368295 TI - Hypoglycemia but not hyperglycemia induces rapid changes in pancreatic beta-cell gene transcription. AB - The purpose of these studies was to quantify several mRNAs expressed specifically in pancreatic islet cells and known or postulated to be important for insulin release after acute well defined alterations in levels of plasma glucose. Glucose levels were maintained at 50, 120, or 180 mg/dl (2.8, 6.7, or 10 mM) for 3 h in conscious unrestrained rats. Hypoglycemia (for 3 h) caused significant decreases in pancreatic content of mRNAs for insulin 2 and GLUT-2 to 55 and 34% of control values, respectively. There were no significant changes in insulin 1, amylin, glucokinase, or glucagon mRNAs. Unprocessed insulin 1 and 2 mRNA precursors were decreased to 17 and 10% of levels in controls, consistent with effects of short term hypoglycemia on new mRNA synthesis. Hyperglycemia (for 3 h) caused no increase in pancreatic content of any mRNA measured. To discriminate between effects of hypoglycemia and hyperinsulinemia in the hypoglycemic animals, rats were made hypoglycemic by infusion with etomoxir, a carnitine palmitoyltransferase I inhibitor that lowers glucose in the fasted (glycogen depleted) state by inhibiting hepatic gluconeogenesis. A single dose of this agent caused a decrease in glucose from 120 mg/dl (6.7 mM) to 80 mg/dl (4.4 mM) and significantly decreased insulin mRNA and pre-mRNA. These results are consistent with the hypothesis that glucose modulates islet cell gene transcription directly. They indicate that the range of glucose concentrations that modulate gene transcription differs from the levels of glucose that alter both insulin biosynthetic and secretion rates. PMID- 8368296 TI - Endothelin-1: a new autocrine/paracrine factor in rat testis. AB - Cultured Sertoli cells of 20-day-old rats were found to produce and release endothelin-1-like immunoreactivity (ET-1-LI) under follicle-stimulating hormone control. The elution profile of ET-1-LI from extracts of spent Sertoli cell culture medium corresponds to that of synthetic ET-1, suggesting a testicular production of authentic ET-1. In contrast, the conditioned medium from rat Leydig cells did not contain ET-1-LI. Immunohistochemical studies confirmed that, in 20 day-old rats, the positive staining was confined to some Sertoli cells, whereas interstitial cells were negative. In the adult rat testis the positivity was not limited to the tubular compartment (Sertoli cells) but was also present in the interstitium. A high concentration (13 pmol/mg protein) of high-affinity (dissociation constant = 0.6 nM) 125I-labeled ET-1 binding sites was present in Leydig cells. These sites bind ET-1 and ET-2 with 1,000-fold higher affinity than ET-3, suggesting that they correspond to the subtype ETA of the ET receptors. Specific 125I-ET-1 binding sites are present also in Sertoli cells but are 50 fold less concentrated than in Leydig cells. Our results suggest an autocrine/paracrine role for ET-1 in rat testis. PMID- 8368297 TI - Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity. AB - To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368298 TI - Plasma NE concentrations do not accurately reflect sympathetic nervous system activity in human sepsis. AB - Plasma norepinephrine concentrations ([NE]) when raised in patients with sepsis are thought to indicate increased activity of the sympathetic nervous system (SNS). However, increased SNS activity may occur without a concomitant rise in plasma [NE]. Measurement of NE kinetics (clearance and spillover) is a more accurate and direct assessment of SNS activity. In the present study plasma [NE] and NE kinetics were measured in six patients with intra-abdominal sepsis (septic) using tritiated NE infused to achieve a plateau plasma concentration. The measurements were repeated in the same patients after they had recovered (nonseptic). NE clearance and spillover were both significantly higher (P < 0.05) in the septic compared with the nonseptic state. However, there was no statistically significant difference in plasma [NE] between the two conditions. Plasma [NE] indicates no alteration in SNS activity during the septic state, whereas NE kinetics indicate increased activity of the SNS during sepsis. The results suggest that plasma [NE] is a poor indicator of SNS activity during septic illness. PMID- 8368299 TI - Impaired febrile responses of aging mice are mediated by endogenous lipocortin-1 (annexin-1). AB - The mechanisms underlying age-related impairments in febrile responses were investigated in female C57Bl/lcrf-a(t) mice. Injection of norepinephrine, to assess total thermogenic capacity, significantly increased oxygen consumption (VO2) in all age groups, although the responses of the aged mice were significantly reduced. Injection of lipopolysaccharide or murine interleukin-1 beta (mIL-1 beta) significantly increased body temperature and VO2 in the young and adult mice but not in the aged mice. The impaired responses to mIL-1 beta in the aged mice were normalized by either injection of the glucocorticoid receptor antagonist RU-38486 or by injection of an antiserum to lipocortin-1 or its purified immunoglobulin G fraction. Injection of prostaglandin E2 significantly increased VO2 and body temperature in all age groups. Resting plasma corticosterone concentrations were significantly elevated in the aged and adult mice, whereas injection of mIL-1 beta significantly raised plasma corticosterone concentrations in all animals. These findings indicate that the impaired febrile response of aged female C57Bl/lcrf-a(t) mice may be caused by increased concentrations and/or sensitivity to endogenous glucocorticoids. The impaired febrile responses of aged mice appear to be mediated by endogenous lipocortin-1. PMID- 8368300 TI - Intravenous glucose tolerance test-derived glucose effectiveness in physically trained humans. AB - Glucose effectiveness (SG) and insulin sensitivity of sedentary and physically trained males were estimated by the minimal model approach. Trained subjects, who ran 86 +/- 10 km/wk and had 37% higher maximal oxygen consumption than that of sedentary subjects (56.2 +/- 1.2 vs. 40.9 +/- 1.4 ml.kg-1 x min-1, P < 0.01), were studied 16 h and 1 wk after their last training session. After overnight fasting, glucose was administered intravenously (300 mg/kg body wt) within 2 min, and insulin was infused (approximately 13-20 mU/kg given over 5 min) from 20 to 25 min after administration of glucose. Glucose disappearance constant values as an estimate of glucose tolerance were significantly higher in trained subjects after 16 h and 1 wk of their training session (3.29 +/- 0.48 and 3.60 +/- 0.64%/min) than in sedentary subjects (1.92 +/- 0.30%/min, P < 0.05). Insulin sensitivity in trained subjects measured after 16 h and 1 wk of their last training session (26.2 +/- 4.4 and 24.3 +/- 6.0 x 10(-5) min-1 x pM-1) was also higher than that of sedentary subjects (10.3 +/- 1.2 x 10(-5) min-1 x pM-1, P < 0.05). SG, the ability of glucose itself to increase peripheral glucose uptake and suppress hepatic glucose output, was significantly higher in trained subjects after 16 h and 1 wk of their last training session (0.028 +/- 0.003 and 0.030 +/- 0.004/min) than in sedentary subjects (0.017 +/- 0.002/min, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368301 TI - LH pulsatility, biopotency, and clearance during undernutrition in orchidectomized mature rats. AB - The effect of food restriction on circulating luteinizing hormone (LH) levels in orchidectomized rats is controversial. The present study demonstrates that decreasing food intake by 50% for 3-10 days in orchidectomized rats increases LH pulse amplitude, length, area under pulse curve, and mean levels but decreases LH pulse frequency compared with ad-lib fed, orchidectomized controls. The effects on pulsatile LH secretion of food reduction by 50% with or without dilution by cellulose to maintain food volume in orchidectomized rats were also examined. Food volume influences pulsatile LH secretion independent of macronutrient effect after 3 days of food restriction, but subsequently macronutrient deprivation predominates. The exaggerated increase in LH levels in orchidectomized rats subject to food restriction for 7 days was not due to immunochemical or chromatographic heterogeneity or alteration in biopotency of circulating LH molecules. Intravenously injected 125I-labeled rat LH analyzed by noncompartmental modeling revealed that neither LH clearance nor mean residence time was reduced by food restriction. We conclude that during food restriction in orchidectomized rats, increases in LH pulse amplitude exceed and precede the decreases in LH pulse frequency, although the early changes in pulse amplitude are predominantly due to reduced food volume rather than macronutrient deprivation. PMID- 8368302 TI - Impact of chronic stress hormone infusion on hepatic carbohydrate metabolism in the conscious dog. AB - The effects of chronic administration of counterregulatory hormones on hepatic glycogenolysis and gluconeogenesis were investigated. We studied 14 20-h fasted conscious dogs prior to (day 0) and after a 70-h stress hormone (SHI, n = 7) or saline (n = 7) infusion (day 3). Glucose production and gluconeogenesis were assessed using tracer and arteriovenous difference techniques. SHI increased plasma glucagon, cortisol, epinephrine, and norepinephrine levels approximately fivefold. SHI increased the arterial plasma glucose and insulin concentrations (110 +/- 2 to 204 +/- 19 mg/dl and 13 +/- 2 to 36 +/- 3 microU/ml on day 3). Tracer-determined glucose appearance and net hepatic glucose output were increased 80 and 60%, respectively. Net hepatic lactate uptake and fractional extraction were increased by 11.2 +/- 3.8 and 0.51 +/- 0.18 mumol.kg-1 x min-1, respectively, as was net hepatic glycerol uptake (1.0 +/- 0.6 mumol.kg-1 x min 1). Net hepatic fractional alanine extraction was also increased by 0.37 +/- 0.03 mumol.kg-1 x min-1; however, net hepatic alanine uptake was not altered. The efficiency of alanine conversion to glucose almost doubled (0.33 +/- 0.05 to 0.59 +/- 0.09). Renal glucose production was also increased, accounting for 33% of the increase in glucose turnover. This increase was paralleled by an increase in renal gluconeogenic precursor uptake. In conclusion, SHI created marked hyperglycemia and hyperinsulinemia and elevated glucose production from both the liver and the kidney, with gluconeogenesis accounting for approximately 70% of the response. PMID- 8368303 TI - Stimulation of the renin-angiotensin system by growth hormone in Lewis dwarf rats. AB - A genetically growth hormone (GH)-deficient strain of Lewis rats was used to test the hypothesis that the actions of GH on electrolyte and fluid homeostasis are mediated by the renin-angiotensin-aldosterone system (RAAS). Dwarf rats injected with recombinant bGH (2 mg.kg-1 x day-1) for 7 days (group GH1+) and 28 days (group GH4+), respectively, were compared with saline-injected dwarf (group GH-) and normal (group N) Lewis rats. GH decreased Na+ excretion and increased renal glomerular filtration rate in dwarf rats. The dietary intake and plasma concentrations of Na+ and K+ remained unchanged. GH increased plasma insulin-like growth factor I (IGF-I) concentrations in dwarf rats (GH - = 109 +/- 9, GH1+ = 184 +/- 5, GH4+ = 189 +/- 28, N = 477 +/- 29 ng/ml plasma). Plasma angiotensinogen increased towards the levels found in normal Lewis rats (GH- = 859 +/- 38, GH1+ = 906 +/- 18, GH4+ = 1,027 +/- 19, N = 1497 +/- 80 ng angiotensin I/ml plasma); plasma renin activity increased above that of the normal Lewis (GH- = 10.2 +/- 0.6, GH1+ = 11.7 +/- 0.7, GH4+ = 16.7 +/- 2.4, N = 10.6 +/- 0.8 ng angiotensin I.ml plasma-1 x h-1). Plasma aldosterone, corticosterone, and triodothyronine concentrations were unchanged by GH treatment. Angiotensin II receptor densities in GH- rats (liver = 356 +/- 23, kidney = 228 +/- 28, adrenal = 478 +/- 58 fmol/mg protein) were upregulated by GH (GH4+ rats; liver = 573 +/- 27, kidney = 360 +/- 86, adrenal = 721 +/- 78 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368305 TI - On the measurement of turnover in vivo. PMID- 8368304 TI - Characterization of osteogenic response to mechanical stimulation in cancellous bone of rat caudal vertebrae. AB - We have recently developed an experimental model in which pins, inserted into the 7th and 9th caudal vertebrae of 13-wk-old rats, are used to load the 8th caudal vertebra in compression. We have now applied this model to assess the responsiveness of rat cancellous bone to mechanical stimulation. We found that daily exposure to loads that induce strains similar to those observed in bone during relatively gentle physical activity, for 30 cycles/day, increased the rate of lamellar bone formation on cancellous surfaces by up to 140-fold. Bone formation rate showed a highly significant (P < 0.0001) correlation with the number of days for which the bones were loaded and with the size of the load. A single loading episode of 300 cycles, representing a 10-min period of loading, increased bone formation to 24 times that in nonloaded controls. Indexes of bone resorption were essentially the inverse of the bone formation parameters. These experiments show that rat cancellous bone is exquisitely sensitive to mechanical stimulation and suggest that the mechanical environment is a major determinant of the physiological behavior of mammalian cancellous bone. PMID- 8368307 TI - Central and peripheral effects of CCK receptor antagonists on satiety in dogs. AB - The role of cholecystokinin (CCK) as a central and peripheral satiety factor was studied using the CCK-B (L-365,260) and CCK-A (MK-329) receptor antagonists in esophageal-fistula dogs. Suppression of feeding was induced by either balloon gastric distension or small bowel nutrient infusion and was measured as the volume sham fed. Intracerebroventricular L-365,260 abolished satiety behavior from gastric distension (volume sham fed 2,667 +/- 211 ml vs. vehicle alone 1,217 +/- 446 ml, P < 0.05) but not small bowel infusion. Intravenous MK-329 abolished satiety behavior from small bowel infusion (volume sham fed 1,900 +/- 521 ml vs. vehicle alone 210 +/- 198 ml, P < 0.05) but not from gastric distension. The volume sham fed after intracerebroventricular MK-329 with balloon gastric distension or small bowel infusion did not differ from control. These results suggest that, in the brain, CCK is a physiological mediator of satiety behavior from gastric distension but not small bowel nutrients and, in the periphery, CCK is a physiological mediator of satiety behavior from small bowel nutrients but not gastric distension. PMID- 8368306 TI - Trefoil peptides: a newly recognized family of epithelial mucin-associated molecules. AB - Members of the trefoil family of peptides are generally small stable secreted molecules, structurally related by the presence of one, or up to six, compact 6 cysteine motifs. Several trefoil peptides are expressed in mammalian gut and Xenopus gut and skin, often in association with mucins. Chronic ulcerative conditions of the gut, such as Crohn's disease, result in the growth of glandular structures of the ulcer-associated cell lineage (UACL) that secrete epidermal growth factor/urogastrone, transforming growth factor-alpha, and at least three trefoil peptides [pS2, human spasmolytic polypeptide (hSP), and intestinal trefoil factor (hITF/hP1.B)]. Neuroendocrine and goblet cells near the UACL are "recruited" into expressing pS2 and hSP, but the purpose of this concerted expression is unclear. A role in mucosal healing has been proposed. Biological functions of trefoil peptides have been difficult to establish. Pancreatic spasmolytic polypeptide of porcine origin inhibits gastric acid secretion and smooth muscle contraction and is a growth factor for some cultured cells, but pS2, once thought to be breast cancer specific, is not a mitogen. Recombinant trefoil peptides have allowed localization of binding sites and will allow structure-activity relationships to be studied, once the functions are clear. PMID- 8368308 TI - Interaction between cholephilic anions and bile acid transport across basal membrane of human trophoblast. AB - The sensitivity of radiolabeled bile acid (BA) binding and transport by basal plasma membrane (BPM) vesicles of human trophoblast to cholephilic organic anions (COAs) was studied by a rapid filtration technique. Glycocholate (GC) efflux from preloaded (15 microM GC) vesicles was investigated in the presence of 300 microM COAs at the trans-side of the membrane. Bilirubin (BR) diglucuronide and rose bengal induced a very strong transstimulating effect, whereas phalloidin and phenol red showed a negligible effect. This effect was from strong to moderate for indocyanine green > bromosulfophthalein (BSP) > or = fusidic acid > or = phenolphthalein > or = BR ditaurate > or = rifamycin SV > or = rifampicin. BSP induced transstimulation was not additive to the "velocity effect" previously reported for bicarbonate. At the cis-side, BSP reduced the saturable component of taurocholate (TC) binding to BPM vesicles. BSP also induced a partial and mixed type of inhibition both in TC uptake [inhibitor constant (Ki) 227 microM] and efflux (Ki 209 microM). Two binding sites with overlapping specificity for BAs and other COAs are proposed in this carrier, the site for non-BA COA presumably corresponding to that for bicarbonate. In summary, the results indicate that several COAs can act as potential substrates for the BA carrier located at the BPM of human trophoblast. This stresses the "biliary-like" role of the placenta and suggests the possibility of developing new functional tests for this organ on the basis of fetal-maternal transfer of nontoxic cholephilic dyes. PMID- 8368309 TI - Physiological and morphological properties of neurons in sphincter of Oddi region of the guinea pig. AB - Intracellular recordings and dye injections were used to investigate neurons located in ganglia of the sphincter of Oddi (SO) region in guinea pigs. Four types of neurons were encountered based on physiological properties. The two most abundant types, tonic and phasic, had similar membrane characteristics and morphologies but yet could be differentiated by their spiking characteristics. Tonic cells spiked throughout a depolarizing current pulse and were sometimes spontaneously active. Phasic cells fired only a single action potential at the onset of a current pulse regardless of stimulus amplitude or duration. Both tonic and phasic cells had Dogiel type I morphologies. They typically had a single long process and several very short processes emanating from the soma. NADPH diaphorase activity was demonstrated in cells with similar morphologies, indicating that nitric oxide may be an intrinsic transmitter in some of these cells. Cells with a prolonged afterhyperpolarization (AH cells), similar to the type 1/AH cells of the gut, were rarely encountered. This finding was consistent with the observation that very few calbindin D-immunoreactive neurons exist in this region. Action potentials could not be generated in the fourth type of neuron, called nonspiking neurons, even though they did receive synaptic input. Most tonic and phasic cells received at least one nicotinic fast excitatory postsynaptic potential (EPSP). In addition, both slow EPSPs and inhibitory postsynaptic potentials were observed. Most AH cells received only slow excitatory synaptic input. PMID- 8368310 TI - Cholinergic regulation of guinea pig duodenal bicarbonate secretion. AB - Although it is well known that vagal stimulation induces duodenal HCO3- secretion, there is presently no information about the nature of the cholinoceptor and the intracellular signals involved. In a series of experiments performed in a guinea pig duodenal loop model in situ, intravenous carbachol, atropine, pirenzepine, and hexamethonium were used to determine the extent of cholinergic stimulation and the types of cholinoceptors. Carbachol (2 micrograms.kg-1.5 min-1) stimulated HCO3- secretion threefold, and atropine (0.1 mg.kg-1.5 min-1) and pirenzepine (1 mg.kg-1.5 min-1) both abolished this effect. In addition, hexamethonium (0.3 mg.kg-1.5 min-1) inhibited carbachol-stimulated duodenal HCO3- secretion. Vasoactive intestinal peptide (VIP, 5 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, and this action was partly inhibited by atropine (0.1 mg.kg-1.5 min-1) but not by pirenzepine (1 mg.kg-1.5 min-1). [4Cl-D-Phe6,Leu17]VIP (3.3 mg/kg), an antagonist to VIP, reduced basal, VIP stimulated, and carbachol-stimulated HCO3- secretion. To examine the role of Ca2+ in this process, Ca2+ ionophore A23187, verapamil, and nifedipine were employed. A23187 (5, 50, 500 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, an effect blocked by the VIP antagonist, and modestly augmented the effect of carbachol. Verapamil (0.2 mg.kg-1.5 min-1) and nifedipine (1.7 mg.kg-1.5 min-1) stopped the effect of carbachol on duodenal HCO3- secretion. These results suggest, that in cholinergic regulation of duodenal HCO3- secretion, the M cholinoceptor pathway, Ca2+, and VIP are involved. PMID- 8368311 TI - Effects of ammonium ion and ammonia on function and morphology of in vitro frog gastric mucosa. AB - The effects of ammonium ion (NH+4) and ammonia (NH3) on function and morphology of gastric epithelial cells were studied in intact sheets of in vitro frog (Rana catesbeiana) gastric mucosa. Luminal 115 mM NH4Cl at luminal pH 8.0 (calculated [NH3] 2.7 mM), but not at 5.0 (calculated [NH3] 3 microM) induced 1) an increase in intracellular pH (pHi) in oxynticopeptic cells (OPC) and decreases in transmucosal potential difference (PD) and electrical resistance (R) in resting tissues, 2) a decrease in histamine-stimulated H+ secretion and an increase in H+ backdiffusion after removal of luminal NH4Cl, and 3) augmented acidification of OPC during luminal acidification. Serosal 30 mM NH4Cl at serosal pH 7.2 (calculated [NH3] 0.47 mM) induced 1) an increase in pHi in OPC and inhibition of the alkalinization of OPC after removal of ambient Cl-, 2) a decrease in PD associated with the increase in R and decrease in short-circuit current, effects attenuated by serosal 15 mM K+, accentuated by 0.2 mM Ba2+, and abolished by removal of ambient Cl-, 3) a sudden drop of PD in resting, but not in stimulated tissues, effects prevented by high serosal pH (7.8), serosal HCO3-, or removal of luminal Cl-, 4) a decrease in histamine-stimulated H+ secretion and an increase in H+ backdiffusion after removal of NH4Cl, and 5) augmented acidification of OPC during luminal acidification. These results suggest that 1) luminal NH3, but not NH+4, increases backdiffusion of H+ from the lumen to the mucosa, 2) serosal NH3 and/or NH+4 induces depolarization of OPC and decreases electrogenic Cl- transport, thereby attenuating the activity of the basolateral Cl(-)-HCO3- exchanger in OPC, and 3) both of these effects contribute to the augmented acidification of OPC during exposure to high luminal [H+]. PMID- 8368312 TI - PACAP is a stimulator of neurogenic contraction in guinea pig ileum. AB - The myotropic effect of pituitary adenylate cyclase-activating polypeptide (PACAP), a novel brain-gut peptide with high sequence homology to vasoactive intestinal polypeptide (VIP), was studied in the isolated guinea pig ileum in vitro. PACAP contracts the guinea pig ileum significantly more potently and efficiently compared with VIP. PACAP-induced contraction was abolished by tetrodotoxin, dynorphin, and somatostatin, partially reduced by atropine, and not affected by ganglionic and adrenergic blockade. The atropine-resistant component was sensitive to spantide, to the induction of tachyphylaxis with substance P, and to omega-conotoxin. Ileal strips desensitized to PACAP did not respond to VIP, although they maintained their sensitivity to PACAP after desensitization to VIP. COOH-terminal-truncated derivatives of PACAP exhibited full biological activity, although some of them showed substantially reduced potency. Deletion of NH2-terminal amino acids abolished biological activity. PACAP produced a concentration-dependent increase in the release of [3H]acetylcholine from longitudinal muscle-myenteric plexus preparations preloaded with [3H]choline. This effect was Ca2+ dependent, tetrodotoxin sensitive, and resistant to hexamethonium and scopolamine. In contrast, PACAP inhibited release of acetylcholine evoked by field stimulation. In summary, PACAP-induced contraction of the guinea pig ileum is mediated via release of acetylcholine and substance P through interaction with PACAP-1 and VIP/PACAP-2 receptors. PACAP has to be added to the list of myotropic neuropeptides of the gastrointestinal tract. PMID- 8368313 TI - Mechanoreceptors sensitive to flow at the gastroduodenal junction of the cat. AB - Vagal afferent activity was recorded from the cervical vagus simultaneously with intraluminal pressure and flow rate at the proximal duodenum, in cats anesthetized with pentobarbital sodium. Thirty-seven mechanoreceptors that adapted slowly to maintained pressure changes were found to be sensitive to the flow of saline through the pylorus. The passage of liquid was associated with an increase of pressure equal to one-tenth of that necessary to trigger a response of the receptors during the distension of a small balloon. The frequency of discharge was increased by the passage of liquid for positive back pressures < or = 1.5 kPa but not when back pressure was negative. The relationship between the discharge of the receptor and the flow rate was complex and showed an hysteresis. We conclude that there exist slowly adapting mechanoreceptors sensitive to distension of the duodenum that can also sense the passage of liquid. PMID- 8368314 TI - Decreased expression of protooncogenes c-fos, c-myc, and c-jun following polyamine depletion in IEC-6 cells. AB - Direct exposure of small intestinal mucosal cells to luminal polyamines stimulates proliferation. This study tests the hypothesis that the protooncogenes c-fos, c-myc, c-jun, and junB are involved in the mechanism by which polyamines modulate mucosal growth. Studies were conducted in the IEC-6 cell line, derived from rat small intestinal crypt cells. Cells were grown in Dulbecco's minimal essential medium containing 5% dialyzed fetal bovine serum (dFBS) in the presence of absence of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, which is the rate-limiting enzyme for polyamine synthesis. Cellular polyamine levels, cell growth, and relative abundance of c fos, c-myc, c-jun, and junB mRNAs, were measured at 1, 2, 4, 6, 8, and 12 days after initial plating. The intracellular polyamines, spermidine and spermine, and their precursor, putrescine, in DFMO-treated cells decreased significantly at 2 days and remained depleted thereafter. Although DFMO profoundly decreased growth and final cell number, both control and DFMO-treated cells entered a plateau phase by 6 days. In control cells, c-myc and c-jun mRNA levels significantly increased on days 4-6 and then returned to a basal level of expression, which was maintained thereafter. c-fos mRNA in quiescent cells after 24 h serum deprivation was significantly stimulated by 5% dFBS, although a steady-state level of c-fos mRNA was undetectable in control cells. Treatment with DFMO not only prevented increased expression of c-myc and c-jun protooncogenes at 4 days, but also significantly reduced steady-state levels of c-myc and c-jun mRNA between 6 and 12 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368315 TI - Identification of a 5-hydroxytryptamine (5-HT2) receptor on guinea pig small intestinal crypt cells. AB - Radioligand labeling of [3H]ketanserin was examined in suspensions of dispersed guinea pig small intestinal mucosal cells prepared by modification of the EDTA chelation method described by M. M. Weiser (J. Biol. Chem. 248: 2536-2541, 1973). Preferential incorporation of [3H]thymidine was used to confirm that suspensions were enriched in crypt cells. At 25 degrees C, binding of [3H]ketanserin to dispersed enterocytes was rapid, maximal by 5 min, saturable (dissociation constant = 1.5 nM), 65 +/- 5% specific, stable, and reversible. The maximal number of binding sites per cell was 92,000 (range 86,000-105,500). Binding was temperature dependent, with maximal binding at 37 degrees C, and was inhibited by 5-hydroxytryptamine (5-HT) (half-maximal inhibition of [3H]ketanserin binding observed in response to 1 microM 5-HT) and ketanserin (half-maximal inhibition of [3H]ketanserin binding observed in response to 1 nM ketanserin) but not by the 5 HT1P antagonist N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide (5-HTP-DP) or the 5-HT3 antagonist 3-tropanyl-indole-3-carboxylate methiodide (ICS-205-930). The second messenger system coupled to the putative mucosal 5-HT2 receptor was examined. 5-HT stimulated a concentration-dependent production of inositol 1,4,5 trisphosphate (IP3) in the dispersed enterocytes. This was maximal at 1 min and was inhibited in a concentration-dependent manner by ketanserin. 5-HTP-DP and ICS 205-930 had no effect on 5-HT-stimulated production of IP3. These data provide evidence for the existence of a mucosal 5-HT2 receptor located on guinea pig small intestinal crypt cells. PMID- 8368316 TI - Intracellular alkalinization stimulates bile flow and vesicular-mediated exocytosis in IPRL. AB - Intracellular pH recovery from an acute alkaline load in rat hepatocytes is mediated by a Cl(-)-HCO3- exchanger, which is electroneutral, Na+ independent, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) sensitive. Stimulation of this Cl(-)-HCO3- exchanger requires intact microtubules, suggesting that vesicular transport may be required to activate this exchanger. To determine if intracellular alkalinization stimulates biliary HCO3- excretion and bile flow in the intact liver by vesicle-mediated exocytosis, isolated perfused rat livers (IPRL) were alkalinized by two protocols. Isohydric changes in CO2 and HCO3- concentrations induced transient increases in bile flow by 36% (P < 0.01), which were abolished by DIDS (0.01 mM), inhibited by pretreatment with colchicine (P = 0.01), but not affected by membrane depolarization with the K(+)-channel blocker BaCl2 (1 mM). Similarly, perfusion with 20 mM NH4Cl produced a 42% increase in bile flow (P < 0.01) and a 26% increase in biliary HCO3- excretion. Both the increases in bile flow and HCO3- excretion were almost completely blocked by DIDS and inhibited by pretreatment with colchicine (P < 0.01). Biliary excretion of horseradish peroxidase was also increased during intracellular alkalinization with either protocol (P < 0.01). These findings suggest that intracellular alkalinization stimulates bile flow and biliary HCO3- excretion. Microtubule-dependent vesicular-mediated exocytosis is involved in this response. PMID- 8368317 TI - Effect of maternal sialoadenectomy on ontogenic response of rat gastric mucosa to luminal H+. AB - Epidermal growth factor (EGF) originating from salivary glands has been shown to affect the development and integrity of rodent gastrointestinal mucosa. Because newborn rats receive EGF from maternal milk, we have examined the effect of sialoadenectomy as a method of depleting EGF in milk on the resistance of neonatal rat mucosa to luminal H+. Rat dams were sialoadenectomized (SALX) or sham operated 5 days after parturition. Experiments were performed on newborns 10 22 days old. Mucosal permeability responses to intraluminal HCl (300 mM) were examined in terms of luminal appearances of Na+, K+, and protein and H+ loss. EGF levels in maternal milk were determined by immunoassay. In rat pups from control litters, luminal HCl resulted in an age-associated increase in cation and protein flux across the gastric mucosa. Luminal cation and protein fluxes observed in 10- to 18-day-old rat pups from SALX dams were not significantly different from similarly aged rats from control dams. However, in 19- to 22-day-old rats from SALX dams, the permeability responses to luminal HCl were exacerbated compared with similarly aged neonates from control dams. These responses were reduced by treatment with EGF. EGF levels in milk from sham-operated and SALX dams were not significantly different in the 10- to 16-day lactational period. However, in SALX dams EGF was significantly reduced at 19 and 22 days. Chromatographic elution pattern of milk EGF was dissimilar to the pattern exhibited by submandibular gland EGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368318 TI - TGF-alpha is a potent mitogen for primary cultures of guinea pig gastric mucous epithelial cells. AB - Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) are thought to be important in gastric epithelial proliferation and repair. It was therefore of interest to determine if TGF-alpha and EGF promoted the growth of an in vitro primary culture system of guinea pig gastric mucous epithelial cells (MEC). MEC were isolated from guinea pig stomachs and cultured in 24-well Primaria plates with DMEM with or without 10% fetal calf serum (FCS). Growth of MEC was determined by changes in [3H]thymidine uptake, cell counts, protein, and DNA. The sources of peptides were human recombinant TGF-alpha (recTGF-alpha) and human recombinant EGF (recEGF). Both recTGF-alpha and recEGF were used at equipotent doses as determined by competing activity in a 125I-labeled TGF-alpha radioreceptor binding assay using A-431 cells. Basal growth (no peptides) of MEC in 10% FCS was dependent on the initial plating density. Under serum-free conditions, [3H]thymidine uptake increased up to 17-fold at 24 h with recTGF alpha (0.1-10.0 nM) compared with only a 4-fold increase using rec-EGF (0.1-10.0 nM) at this same time period. Under serum-free conditions, recTGF-alpha (0.01 10.0 nM) increased cell counts up to 4.9-fold over control cultures, whereas similar does of recEGF produced a 2.5-fold increase in cell counts. Administration of recEGF 1 ng/ml) resulted in a 1.9-fold increase in the 4.8-kb TGF-alpha mRNA transcript, and TGF-alpha protein immunoreactivity was found in both 24-h conditioned media and cell lysates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368319 TI - Cell survival in rabbit gastric glands: effect of extracellular pH, osmolarity, and anoxia. AB - Although backdiffusion of luminal acid is regarded as a common mechanism of gastric injury, the extracellular pH (pHo) at which cells are irreversibly injured is not well defined. Exclusion of the fluorescent dye propidium iodide was used to estimate cell survival in rabbit gastric glands incubated in buffers of pHo 8.0-2.0. Mean survival (+/- SE) for n = 6 experiments at 2 h in a HEPES buffer of 300 mosM at pHo 8.0, 7.0, 6.0, 4.0, and 2.0 was 80 +/- 3, 91 +/- 2, 90 +/- 2, 71 +/- 2, and 17 +/- 4%, respectively. Survival at acidic pHo was improved in a high KCl buffer: 78 +/- 3 and 38 +/- 7% at pHo 4.0 and 2.0, respectively. Survival in HCO3- buffers was 73 +/- 3, 88 +/- 2, and 92 +/- 3% at pHo 8.0, 7.4, and 6.0. Brief (5 min) exposure to pHo 4.0 followed by reexposure to pHo 7.4 had no effect on acid secretion as estimated by [14C]aminopyrine uptake or cellular viability over 4 h. The influence on cell survival of changes in pHo under conditions of chemical anoxia and in buffers of different osmolarity was investigated. Chemical anoxia was induced using 2.5 mM KCN and 2.0 mM iodoacetic acid (IAA) to inhibit oxidative phosphorylation and anaerobic glycolysis. Survival in glands exposed to KCN and IAA in HEPES buffer was 54 +/- 5, 82 +/- 3, and 87 +/- 2% at pHo 8.0, 7.0, and 6.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368320 TI - Altered jejunal potassium (Rb+) transport in piglet rotavirus enteritis. AB - To determine the mechanisms of K+ loss in viral diarrhea, K+ fluxes (estimated by tracer Rb+ flows) across piglet jejunum in Ussing chambers were determined. Normal jejunum was characterized by an indomethacin-sensitive short-circuit current and a small K+ secretory flow. Rotavirus-infected gut secreted K+ at high rates, probably resulting from increased prostaglandin generation because secretion was abolished by indomethacin. Tissues pretreated with indomethacin responded to 8-bromoadenosine 3',5'-cyclic monophosphate acid and 16,16-dimethyl prostaglandin E2 with K+ secretion. The secretory response in rotavirus-infected jejunum was no greater than that in normal tissue. Serosal addition of Ca2+ ionophore A23187 caused K+ secretion in normal but not rotavirus-infected jejunum. To inhibit the basolateral uptake of K+ and reduce the driving force for secretion, ouabain was added to the bath. Ouabain unmasked a K+ absorptive process in normal intestine, which was not seen in rotavirus-infected tissue. K+ absorption was inhibited by 3-(cyanomethyl)-2-methyl-8-(phenyl-methoxy)imidazo (1,2 alpha)pyridine (Sch-28080) and omeprazole. We speculate that the high fecal K+ losses observed in human rotavirus enteritis might be caused by an imbalance between K+ secretion and an impaired apical K+ absorptive mechanism in the crypt type epithelium. PMID- 8368321 TI - Age-related changes in pulmonary muscarinic receptor binding properties. AB - The goal of this study was to elucidate mechanisms responsible for age-related reductions in responsiveness to cholinergic muscarinic stimulation in guinea pigs, by examining the binding properties of muscarinic receptors and their coupling to guanine nucleotide regulatory proteins as a function of animal age. In addition, the binding constants of three selective muscarinic receptor antagonists pirenzepine, [11-((2-[(diethylamino)methyl]-1-piperidinyl)-acetyl)-5, 11-dihydro-6H-pyrido(2,3)(1,4)benzodiazepine-6-on], and 4-diphenylacetoxy-N methylpiperidine methobromide were examined. We found that there were no changes in either the receptor density or the affinity of the muscarinic receptor with age. There was a significant reduction in the affinity constant for the high affinity agonist binding site in the old tissues (7.63 +/- 0.08) compared with the young tissues (8.31 +/- 0.10). Guanine nucleotides lowered agonist affinity for the receptor in young lungs, however, they had no effect on agonist binding in old tissues. Antagonist competition binding curves in young tissues revealed that 73% of the receptors are of the M2 type, with 27% being of the M3 subtype. In contrast, antagonist competition binding curves in the old tissues revealed that 37% of the receptors were of the M2 subtype, 30% were M3, and 33% were of the M1 subtype. Our studies provide evidence that the loss of sensitivity to cholinergic muscarinic stimulation in the senescent lung may be due to changes in both muscarinic receptor subtypes and receptor coupling to G proteins. PMID- 8368322 TI - Nitric oxide synthesis by rat pleural mesothelial cells: induction by cytokines and lipopolysaccharide. AB - The close proximity of pleural mesothelial cells (PMC) and mononuclear cells during pleural inflammation suggests that leukocyte-derived products (e.g., cytokines) may play an important role in modulating PMC function. The purpose of this study was to determine whether certain cytokines and bacterial products induce PMC to produce nitric oxide (NO). Confluent monolayers of rat PMC were exposed to tumor necrosis factor (TNF), interleukin-1 beta (IL-1), gamma interferon (IFN), or lipopolysaccharide (LPS) individually and in various double and triple combinations for 6-72 h. Concentrations of nitrite and nitrate were quantified and used as indirect indices of NO production. Nitrite/nitrate accumulation was maximal at 72 h, with most of the increase occurring from 48 to 72 h. Maximal nitrite/nitrate production was observed with triple combinations with the combination of LPS, IL-1, and TNF giving the highest concentration (137.4 +/- 2.8 microM). Nitrite/nitrate production was significantly inhibited by NG-nitro-L-arginine methyl ester, suggesting that nitrite and nitrate were derived from the L-arginine-dependent formation of NO. These data indicate that PMC can be induced to produce large amounts of NO in response to specific combinations of proinflammatory cytokines and LPS. PMID- 8368323 TI - Glucocorticoid elevation of mRNA encoding epinephrine-forming enzyme in lung. AB - The epinephrine-forming enzyme phenylethanolamine N-methyltransferase (PNMT) is present in lung and its activity is increased by the glucocorticoid dexamethasone. Chronic administration of dexamethasone (0.5 mg/kg twice daily) doubled levels of mRNA coding for PNMT in rat lung. Administration of the glucocorticoid antagonist RU 486 after 7 days of dexamethasone treated reduced PNMT mRNA by about two-thirds within 24 h. Lung epinephrine (E) levels correlated with lung PNMT activity in these dexamethasone-treated and control rats. In a separate experiment, lung PNMT mRNA levels were nearly tripled 6 h after dexamethasone (1 mg/kg sc). In a third experiment chronic administration of the PNMT inhibitor SKF 64139 (50 mg/kg twice daily) reduced in vitro lung PNMT activity in chronically dexamethasone-treated adrenalectomized rats by approximately 96% and reduced lung E levels by approximately 75%. We conclude that glucocorticoids increase lung PNMT activity by increasing levels of mRNA coding for this enzyme. The data also suggest that a substantial fraction of lung E is locally synthesized. We speculate that enhanced lung E synthesis may participate in glucocorticoid-induced dilation of the bronchioles. PMID- 8368324 TI - Hyperoxic stress elevates p52(PAI-1) mRNA abundance in cultured cells and adult rat pulmonary tissue. AB - Hyperoxic stress alters expression of genes involved in extracellular matrix (ECM) remodeling. To identify novel ECM-associated gene products positively regulated by hyperoxia, rat kidney cells were exposed to 95% O2, and the complement of [35S]methionine-labeled, saponin-resistant, ECM-associated proteins was compared with normoxic controls. O2-stressed cells accumulated significantly greater ECM levels (approximately 3- to 4-fold that of control cells) of a 52-kDa glycoprotein (p52), recently identified as the matrix form of plasminogen activator inhibitor type 1 (PAI-1) (P.J. Higgins, P. Chaudhari, and M.P. Ryan. Biochem. J. 273: 651-658, 1991; P. J. Higgins, M. P. Ryan, R. Zeheb, T. D. Gelehrter, P. Chaudhari. J. Cell. Physiol. 143:321-329, 1990), which peaked at 48 h of exposure. Hyperoxia-associated increases in ECM p52(PAI-1) content reflected parallel elevations in p52(PAI-1) mRNA abundance. Similar results were obtained using secondary cultures of rat pulmonary fibroblasts. This 48-h period of maximal hyperoxia-induced p52(PAI-1) expression in vitro was used to design subsequent in vivo studies. Adult rats were exposed to 99% O2 for 24-50 h, and RNA was extracted from the pulmonary tissue of stressed and control animals. A 5- to 8-fold and 6- to 15-fold increase in lung p52(PAI-1) mRNA content was evident in hyperoxia-treated rats at 24 and 50 h, respectively. All of this increase occurred in the defined 3.2-kb species of rat p52(PAI-1) mRNA. Actin mRNA levels increased three- to sevenfold as a function of hyperoxic stress, whereas catalase and glyceraldehyde-3-phosphate dehydrogenase mRNA abundance was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368325 TI - Smooth muscle myosin regulation by serum and cell density in cultured rat lung connective tissue cells. AB - RNA and protein analyses were used to detect expression of SM1 and SM2 smooth muscle myosin heavy chain (MHC) in cultured adult rat lung connective tissue cells (RL-90). Smooth muscle MHC mRNA expression in confluent cells grown in 10% serum was approximately 50% of the level in adult stomach. Similar results were obtained in cells cultured at low density (25% confluency) in 1% serum. However, in low-density cultures transferred to 10% serum for 24 h, the level of MHC mRNA decreased to approximately 20% of that in adult stomach. Smooth muscle alpha actin showed a pattern of expression similar to that for smooth muscle MHC. Expression of nonmuscle MHC-A mRNA was higher in all culture conditions compared to stomach. MHC-A mRNA expression was less in low-density cultures in low serum and increased when low-density cultures were transferred to 10% serum for 24 h. MHC-B mRNA expression was less in low- vs. high-density cultures. In contrast to MHC-A, however, MHC-B mRNA expression in low-density cultures was higher in low serum. Immunofluorescence and immunoblotting with SM1-specific antibody demonstrated the presence of the SM1 protein isoform as well as reactivity to a protein band migrating slightly faster than SM2. These results demonstrate that cultured rat lung connective tissue cells express smooth muscle MHC and that expression is modulated by culture conditions. PMID- 8368326 TI - Type II pneumocytes secrete vitamin E together with surfactant lipids. AB - Lung surfactant is exposed to strongly oxidizing conditions. We examined the hypothesis that in lung, lipophilic antioxidants are secreted together with surfactant to counteract the peroxidation of surfactant constituents. Lung lavage and the subfractions of the alveolar surfactant contain the lipophilic antioxidants vitamin E, vitamin A, and plasmalogens. The specific radioactivity of vitamin E isolated from serum, lung homogenate, lamellar bodies, and lung lavage increased linearly up to 3 h after intraperitoneal application of [3H]tocopherol. [3H]tocopherol was secreted in situ together with [14C]palmitic acid-labeled phospholipid in response to isoproterenol. Type II cells cultured in presence of [3H]tocopherol or of [3H]cholecalciferol and [14C]palmitic acid responded to isoproterenol by a time-dependent increase in secretion of [3H]tocopherol and of 14C-labeled phospholipids but not of [3H]cholecalciferol. The isoproterenol-stimulated secretion of [3H]tocopherol and of 14C-labeled phospholipids by type II cells is inhibited by surfactant protein A. We conclude that the alveolar surfactant contains lipophilic antioxidants as integral constituents. [3H]tocopherol seems to be secreted together with surfactant. PMID- 8368327 TI - Glucocorticoid regulation of fatty acid synthase gene expression in fetal rat lung. AB - There are developmental and glucocorticoid-induced increases in the rate of fatty acid biosynthesis and in the activity of fatty acid synthase in late gestation fetal lung. We have now measured mRNA levels of fatty acid synthase and of two other enzymes of fatty acid biosynthesis, ATP citrate lyase and acetyl-CoA carboxylase, in developing fetal and postnatal rat lung and in fetal lung explants cultured with and without dexamethasone. There was a developmental increase in the mRNA for fatty acid synthase with the maximum level being reached on fetal day 21 (term is fetal day 22). This profile was similar to that reported for de novo fatty acid synthesis and fatty acid synthase activity. There was a similar but less pronounced developmental increase in the mRNA for ATP citrate lyase and a corresponding increase in its activity. There was no developmental change in the mRNA for acetyl-CoA carboxylase. Dexamethasone increased the level of fatty acid synthase mRNA approximately threefold but had no effect on those for ATP citrate lyase and acetyl-CoA carboxylase. The effect of dexamethasone on fatty acid synthase mRNA was rapid, biphasic, and partly inhibited by actinomycin D and cycloheximide. We conclude that glucocorticoids increase expression of the gene for fatty acid synthase in fetal lung. The effect of the hormone appears to be due to increased transcription and post-transcriptional events and is dependent on protein synthesis. PMID- 8368328 TI - Apoprotein-based synthetic surfactants inhibit plasmic cleavage of fibrinogen in vitro. AB - Fibrinogen (Fbg) leakage and intra-alveolar fibrin accumulation are commonly noticed in adult respiratory distress syndrome and interstitial lung diseases. Activation of the extrinsic coagulation pathway and elevation of antiplasmin- and plasminogen-activator inhibitor levels are assumed to favor alveolar clot formation and to inhibit fibrinolysis under these conditions. We investigated the influence of synthetic surfactants on the plasmic cleavage of fibrinogen in vitro. Fibrinogenolysis was quantified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with densitometric evaluation and fragment E enzyme-linked immunosorbent assay. A synthetic phospholipid mixture (PLM) (dipalmitoyl-DL-alpha phosphatidylcholine:L-alpha-phosphatidyl-DL-gly cer ol: palmitic acid 68.5:22.5:9) caused a dose-dependent inhibition of fibrinogenolysis in a concentration range between 0.1 and 2 mg/ml. This inhibitory capacity was markedly amplified upon reconstitution of PLM with natural and recombinant surfactant protein (SP)-C as well as natural SP-B. Natural SP-A and recombinant SP-A were far less effective in this respect. In the absence of phospholipids, the hydrophobic apoproteins revealed only moderate plasmin inhibitory capacity (recombinant SP-C > natural SP-C and SP-B). Natural calf lung surfactant extract displayed comparable inhibitory capacity on plasmic Fbg cleavage as PLM. We conclude that hydrophobic surfactant material may suppress plasmin activity and thus may contribute to the finding of delayed alveolar fibrin clearance in inflammatory lung diseases with Fbg leakage. PMID- 8368329 TI - Pulmonary surfactant protein A-mediated uptake of phosphatidylcholine by alveolar type II cells. AB - Pulmonary surfactant protein A (SP-A)-mediated uptake of phosphatidylcholine (PC) by alveolar type II cells was investigated. SP-A enhanced the uptake of liposomes containing dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC), or 1,2-dihexadecyl-sn-glycero-3-phosphocholine (DPPC ether), a diether analogue of DPPC, but about twice as much DPPC was taken up by type II cells as PLPC or DPPC-ether. When subcellular distribution was analyzed, 51.3 +/- 2.9% (mean +/- SD, n = 3) of cell-associated radiolabeled DPPC was recovered in the lamellar body-rich fraction in the presence of SP-A, whereas only 19.3 +/- 1.9% (mean +/- SD, n = 3) was found to this fraction in the absence of SP-A. When type II cells were incubated either with DPPC at 0 degree C or with DPPC-ether at 37 degrees C, or no cells were included, low proportions of the cell-associated lipids were present in the fractions corresponding to lamellar bodies even in the presence of SP-A. Anti-SP-A antibody significantly reduced the radioactivity incorporated into the lamellar body fraction. Phosphatidylcholine that had been incorporated into lamellar bodies remained largely intact when SP-A was present. Subcellular fractionations of type II cells with radiolabeled SP-A and DPPC revealed that the sedimentation characteristics of cell-associated SP-A are different from those of DPPC, although a small broad peak of radiolabeled SP A was found in the lamellar body fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368330 TI - Hormonal regulation of inner medullary collecting duct sodium transport. AB - The inner medullary collecting duct (IMCD) is the final arbiter of renal Na+ excretion, and Na+ transport in this segment is controlled by a wide variety of hormones and renal autacoids. This review examines the mechanisms of IMCD Na+ transport and its regulation using results obtained from micropuncture and microcatheterization studies in the intact animal, as well as data from isolated perfused tubules, freshly prepared cell suspensions, and cultured IMCD cells. Where appropriate, results from closely related tissues such as the cortical collecting duct and model urinary epithelia are examined. Na+ reabsorption in this segment occurs predominantly via apical amiloride-sensitive Na+ channels and basolateral Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase). Although there is some evidence for the activities of other transporters such as Na(+) K(+)-2Cl- and Na-Cl cotransporters and Na+/H+ exchanger, their role in Na+ homeostasis remains undefined. Mineralocorticoids augment the activities of both apical Na+ channels and basolateral Na(+)-K(+)-ATPase by a variety of complex mechanisms. Prostaglandin E2 inhibits Na(+)-K(+)-ATPase and appears to mediate the actions of several peptide hormones, including endothelin, interleukin-1, and atrial natriuretic peptide [ANP-(31-67)]. Several peptides in the ANP family [ANP (99-126), urodilatin, and brain natriuretic peptide] bind to guanylate cyclase linked receptors, leading to inhibition of apical Na+ channel function. These mechanisms of regulation of IMCD Na+ transport likely play important roles in total body Na+ balance in health and disease. PMID- 8368331 TI - Sch-28080 inhibits bafilomycin-sensitive H+ secretion in turtle bladder independently of luminal [K+]. AB - To explore the possible contribution of an H-K-adenosine-triphosphatase (H-K ATPase) to H+ secretion (JH) in the isolated turtle bladder, we measured electrogenic JH (JeH) as short-circuit current and total JH (JTH) by pH stat titration in the presence of ouabain at different ambient K+ concentration ([K+]) and during luminal addition of a known gastric H-K-ATPase inhibitor, Schering (Sch)-28080. JH was not reduced by decreasing ambient [K+] to undetectable or very low levels (< 0.05 mM by atomic absorption) and luminal BaCl2 addition to further reduce local [K+] at the apical membrane. These K(+)-removal studies indicate that H+ transport is not coupled to countertransport of K+. JTH did not exceed JeH at any point: in K(+)-free solutions JTH was 0.73 +/- 0.05, and JeH was 0.95 +/- 0.08 mumol/h; in standard (3.5 mM) K+ solutions JTH was 0.72 +/- 0.05 and JeH 0.98 +/- 0.06 mumol/h; in high (118 mM) K+ solutions JTH was 0.65 +/ 0.07 and JeH 0.94 +/- 0.08 mumol/h. Sch-28080 caused a rapid inhibition of JH, with similar half-maximal inhibitory concentrations (IC50) in K(+)-free, standard [K+], and high [K+] solutions. Bafilomycin inhibited JeH and JTH with an IC50 of approximately 100 nM. The observed non-potassium-competitive inhibition of JH by Sch-28080 and the bafilomycin sensitivity distinguish the H-ATPase of the turtle bladder from the gastric H-K-ATPase. The rapidity of the inhibition by Sch-28080 suggests that it acts at an accessible luminal site of the ATPase. PMID- 8368332 TI - Effects of adenosine and angiotensin on macula densa-stimulated renin secretion. AB - The present studies were performed to assess, in the isolated perfused juxtaglomerular apparatus of the rabbit kidney, the effect of exogenous adenosine on renin secretion stimulated by a low NaCl concentration at the macula densa. Addition of adenosine to the bath resulted in a change of renin secretion from 30.4 to 23.9 nGU/min at an adenosine concentration of 10(-6) M (n = 7; P = NS), from 38.6 to 17.9 nGU/min at a concentration of 10(-4) M (n = 7; P = 0.038), and from 18.4 to 5.8 nGU/min at 10(-2) M (P = 0.0053). Addition of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-5) M fully reversed the effect of adenosine at 10(-4) M, but not at 10(-2) M. Inhibition of adenosine breakdown by the adenosine deaminase inhibitor pentostatin (10(-6) M) enhanced the inhibitory effect of adenosine with renin secretion falling from 61.7 to 19.5 nGU/min at 10(-6) M adenosine (P = 0.035) and from 44.7 to 13.5 nGU/min at 10(-4) M adenosine (n = 0.027). A marked inhibition of NaCl-dependent renin secretion was caused by both angiotensin II (P = 0.011) and angiotensin III (P = 0.006), both at 10(-8) M. These results show that adenosine is capable of reducing macula densa-mediated renin secretion, but that this effect, even at very high concentrations or during adenosine deaminase blockade, does not fully mimic the inhibitory potency of increasing luminal NaCl concentration. Because the marked effect caused by angiotensins establishes the potential of this preparation to demonstrate inhibitory hormonal influences, it is concluded that adenosine does not appear to be the sole paracrine factor responsible for the NaCl-induced reduction of renin secretion. PMID- 8368333 TI - Proliferative synergy of ANG II and EGF in porcine aortic vascular smooth muscle cells. AB - To test growth effects of angiotensin II (ANG II) in porcine vascular smooth muscle cells (VSMC) and potential ANG II synergy with epidermal growth factor (EGF), we exposed subconfluent, near-quiescent porcine aortic VSMC to ANG II, EGF, or ANG II + EGF (each 10(-9) M) in Dulbecco's modified Eagle's-Ham's F-12 medium with insulin + 0.4% fetal calf serum (FCS) selected for minimal ANG II degrading capacity. Cell number and DNA and protein synthesis (by [3H]-thymidine and [35S]methionine incorporation, respectively) were determined serially over 1 6 days. ANG II alone induced an early 20% increase and then a plateau in cell number over the 0.4% FCS control (P < 0.01; n = 8), thus without sustained increase in proliferation rate. Yet ANG II alone did not increase fractional DNA or protein synthesis (each as cpm/10(3) cells) and, by flow cytometry, reduced S phase fraction without increase in cell size. EGF alone induced brisk DNA synthesis yet minimal cell division over days 0-4, thus late-cycle arrest. ANG II + EGF, despite no increase in fractional DNA or protein synthesis rates over EGF alone, induced significant indomethacin-resistant dose-dependent (P < 0.001) increase in cell proliferation rate over EGF alone with a median effective dose of 5 x 10(-10) M ANG II, thus proliferative synergy. We propose that 1) ANG II induces a subpopulation of cells arrested in or beyond S phase to proceed through mitosis but does not influence G1 traversal or S phase entry and 2) ANG II + EGF achieve proliferative synergy by complementary actions at sequential cell cycle loci, with EGF supporting progression from G0/G1 to S phase and ANG II inducing completion of mitosis by cells already in or beyond S phase ("late-cycle completion"). PMID- 8368334 TI - Mechanisms of adaptation to proteinuria in adriamycin nephrosis. AB - To evaluate the impact of urinary protein losses on whole body protein turnover (WBPT) independent of acidosis or uremia, we utilized a model of unilateral adriamycin nephrosis. Control rats were matched by weight to nephrotic rats and pair fed 22% protein chow for 14-18 days; urinary urea nitrogen (UUN) was measured on day 12, and leucine turnover measurement was performed on the final day. Growth rates of nephrotic and pair-fed control rats did not differ during the first 2 wk of pair feeding; thereafter, a small difference in growth could be detected. Despite an identical intake of dietary protein, UUN excretion was 29% less in the nephrotic rats (P < or = 0.02). Fasting whole body protein synthesis and degradation did not differ between nephrotic and control rats; in contrast, leucine oxidation decreased by 21% in nephrosis (P < 0.05). On the basis of near normal growth and normal rates of WBPT, we conclude that nephrotic rats fed ad libitum can adapt to the stress of continuous protein losses. A reduction in amino acid oxidation and UUN excretion were the primary mechanisms responsible for protein conservation in experimental nephrosis. PMID- 8368335 TI - Glomerular angiotensin II receptor subtypes during development of rat kidney. AB - We used quantitative autoradiography to investigate distribution of angiotensin II (ANG II) receptor subtypes during development of the kidney in the rat. In fetal, newborn, and 3-day-old rats, immature glomeruli in the form of comma and S shaped bodies, located in the nephrogenic zone of the renal cortex, expressed only the angiotensin AT2 receptor subtype. Conversely, the juxtamedullary glomeruli, in more advanced developmental stages, expressed only the AT1 subtype. Similarly, maturing and fully developed glomeruli, present in 1-, 2-, and 8-wk old rats, expressed only AT1 receptors. In the kidney medulla, there was a similar change in ANG II receptor subtype expression, with the AT2 subtype expressed earlier and the AT1 subtype later during development. Our results demonstrate a selective expression of ANG II receptor subtypes during kidney development. We have found glomerular and medullary AT1 receptors only at developmental stages when kidney function has matured. Conversely, AT2 receptors are expressed only in immature structures, suggesting that they may have a role during kidney organogenesis. PMID- 8368336 TI - Tubular handling of fluid and electrolytes during ovine pregnancy. AB - Pregnancy is characterized by progressive water and sodium accumulation and increases in renal blood flow (RBF) and glomerular filtration rate (GFR). However, the influence of the different nephron segments on the increased tubular reabsorption is controversial. Consequently, four nonpregnant and five pregnant sheep were studied, after chronic instrumentation, to assess salt and water reabsorption in the proximal and distal tubules under basal and volume-loaded conditions. Lithium clearance was used as a marker for proximal tubular reabsorption. Volume loading was achieved by the rapid administration of 1,000 ml isotonic saline followed by 250 ml/h for 2 h. Under basal conditions with reference to the nonpregnant state, pregnant sheep had higher (P < 0.05) levels of right RBF (427 +/- 34 vs. 313 +/- 8 ml/min), GFR (133 +/- 7 vs. 94 +/- 9 ml/min), proximal tubular reabsorption (102 +/- 7 vs. 73 +/- 6 ml/min), distal nephron fluid delivery (31 +/- 2 vs. 20 +/- 2 ml/min), and fractional distal nephron reabsorption of fluid (92 +/- 2 vs. 87 +/- 1%) and sodium (98.8 +/- 0.3 vs. 97.0 +/- 0.7%). However, pregnant animals had significantly (P < 0.05) reduced fractional excretions of fluid (1.6 +/- 0.3 vs. 2.6 +/- 0.2%) and sodium (0.24 +/- 0.06 vs. 0.63 +/- 0.19%), but similar levels of filtration fraction, fractional proximal tubular reabsorption, urine flow, urinary sodium excretion, and osmolar and free water clearance. After saline loading, pregnant sheep excreted significantly (P < 0.05) less sodium (9.2 vs. 28.6%) and water (39.8 vs. 56.5%). Decreases in fractional proximal and distal nephron reabsorption of sodium and water after saline loading were attenuated in pregnant animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368337 TI - Influence of endothelium-derived relaxing factor on renal microvessels and pressure-dependent vasodilation. AB - The influence of endothelium-derived relaxing factor (EDRF) on renal microvessels and autoregulation was visualized in vivo, in the split hydronephrotic kidney of rats. EDRF synthesis was inhibited by local administration of 10(-5) M NG-nitro-L arginine methyl ester (L-NAME). Diameters of arcuate arteries decreased by 17%. In cortical vessels efferent arterioles constricted more (13-16%) than interlobular arteries and afferent arterioles (7-12%). Cortical glomerular blood flow (GBF) decreased by 46% after L-NAME. A similar behavior of blood flow and vascular diameters was also observed in juxtamedullary (JM) arterioles. The responses to acetylcholine but not to sodium nitroprusside were attenuated after L-NAME. After local administration of L-arginine (10(-3) M) diameters of all vessels and GBF increased, vascular responses to L-NAME were blunted. Stepwise reduction of renal perfusion pressure revealed that autoregulation was preserved in cortical vessels after L-NAME. In JM arterioles, which do not autoregulate in female Wistar rats, autoregulation of GBF was enhanced after L-NAME. These data suggest that tonic formation of EDRF influences basal renal hemodynamics to a considerable extent. EDRF may also impair autoregulation of JM glomeruli without disturbing autoregulation of cortical glomeruli. PMID- 8368338 TI - Quantitation and localization of laminin A, B1, and B2 chain RNA transcripts in developing kidney. AB - To quantitate expression of laminin A, B1, and B2 chains during kidney development, we prepared riboprobes of similar size (318-365 nucleotides) and carried out scanning densitometry of Northern blots from newborn mouse and rat kidneys. Much higher expression of B1 than A or B2 mRNAs was observed with an A to-B1-to-B2 ratio of approximately 1:8:4 in mice and approximately 1:12:1 in rats. In addition to the 9.5-kb laminin A chain transcript, we also observed specific hybridization of the A chain probe to approximately 6-kb band in both newborn mice and rats. To localize these mRNAs, newborn rat kidneys were sieved to obtain separate glomerular and tubule fractions. Northern blots from these samples showed that most of the B1, B2, and 9.5-kb laminin A chain mRNAs were in glomerular fractions, whereas tubules contained more of the 6-kb A chain band. Analyses of poly(A)+ mRNA from newborn and adult kidneys showed severalfold decreases in adult RNA encoding the three laminin chains and the alpha 1-chain type IV collagen. However, only a 20% decline from newborn levels was seen for heparan sulfate proteoglycan (HSPG) core protein message. These quantitative results provide additional evidence that different laminin isoforms are present in separate kidney basement membranes and that HSPG core protein synthesis remains at relatively high levels in adult kidneys. PMID- 8368339 TI - Vitamin D3 accelerates PTH-dependent calcium transport in distal convoluted tubule cells. AB - This study examined the interaction of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] and parathyroid hormone (PTH) on Ca2+ uptake, intracellular Ca2+ ([Ca2+]i) and membrane voltage in transformed mouse distal convoluted tubule (DCT) cells. 1,25(OH)2D3 increased PTH-dependent 45Ca2+ uptake by 2 h and was maximally stimulated at 5 h over the range of 10(-11) to 10(-9) M 1,25(OH)2D3. [Ca2+]i was measured in single cells grown on cover slips and loaded with fura-2. In control cells [Ca2+]i averaged 109 nM and was not changed by acute addition of 1,25(OH)2D3 (10(-7) M) alone or by pretreatment with 1,25(OH)2D3 for 5 h. The magnitude of the bPTH-(1-34)-stimulated increase of [Ca2+]i was similar in control cells and in cells pretreated with 1,25(OH)2D3. In cells pretreated with 1,25(OH)2D3 the latency before [Ca2+]i increased, following addition of PTH, was reduced from 8.6 min to 3.5 +/- 0.9 min (P < 0.01). 1,25(OH)2D3 alone had no effect on 45Ca2+ uptake but shortened the time course of PTH-dependent 45Ca2+ uptake. The inactive vitamin D analogue, 25-hydroxyvitamin D3 (10(-7) M) (with or without PTH), did not affect 45Ca2+ uptake. Inhibition of transcription with 5-6 dichloro-1-beta-D- ribofuranosylbenzimidazole abolished the effect of 1,25(OH)2D3, but not that of PTH. Treatment with 1,25(OH)2D3 also decreased the latency but not the magnitude of membrane hyperpolarization induced by PTH. Nifedipine abolished PTH-induced increases of [Ca2+]i and 45Ca2+ entry in cells pretreated with 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368341 TI - Subcellular distribution and guanine nucleotide dependency of COOH-terminal methylation in kidney cortex. AB - The subcellular distribution of COOH-terminal carboxyl methyltransferase and methylated substrates was studied in purified brush-border and basolateral plasma membranes, as well as in crude intracellular membranes and the cytosolic fraction isolated from rat kidney cortex. The three membrane fractions showed intrinsic carboxyl methylation of 21- to 23-kDa proteins, whereas 18- and 41-kDa methylated proteins were observed in the cytosol. In contrast, methylation activities toward N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC), a synthetic farnesylated substrate, were found to be strictly associated with membranes, with no detectable level of activity in the cytosol. Methylation of all membrane associated substrates was inhibited by AFC but remained unaffected by TS-isoD YSKY, a synthetic isopeptide recognized by L-isoaspartyl methyltransferase, suggesting that the membrane-associated substrates were methylated on a COOH terminal isoprenylated cysteine residue. The membrane-associated methylated proteins were tightly bound to the membranes as reflected by their extraction with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate but not with 1 M NaCl or 2 M urea. The nonhydrolyzable analogues of GTP and GDP, guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S) and guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), markedly increased the methylation of the 21- to 23-kDa substrates, whereas ATP gamma S and ADP beta S were without effect. This effect of guanine nucleotides was restricted to endogenous 21- to 23-kDa substrates with no stimulation of methylation of the exogenous substrate, AFC. Our results show a wide distribution of both COOH-terminal protein carboxyl methyltransferase activities and associated methylated substrates in the kidney cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368340 TI - Endothelial modulation of renal interlobar arteries from pregnant rats. AB - The purpose of this study was to determine whether there are gestational effects on 1) the response of resistance arteries from the renal vasculature to phenylephrine and 2) the endothelial modulation of these arteries. Interlobar arteries (200-300 microns ID) were isolated from the kidneys of virgin and pregnant rats at 18-20 days of gestation (term, 22 +/- 1 days) and studied in a pressurized arteriograph system. Intact arteries from virgin and pregnant rats did not differ in sensitivity to phenylephrine. Arteries without endothelium from both groups were more sensitive to phenylephrine than arteries with endothelium. Sensitivity was increased 3.4-fold by endothelial removal in arteries from virgin rats and 1.5-fold in the pregnant group. Concentration-response relationships to phenylephrine were determined in arteries with endothelium and then repeated in the presence of 2.5 x 10(-4) M N omega-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase. All arteries were more sensitive to phenylephrine in the presence of L-NNA, with an average increase of 3.2-fold for the arteries from virgin rats and 1.6-fold from pregnant rats. These results indicate that the increased sensitivity to phenylephrine is primarily due to elimination of endothelium-derived relaxing factor (EDRF) and that basal EDRF activity is decreased during late gestation. To determine whether stimulated endothelium dependent relaxation is enhanced in pregnancy, arteries with endothelium were constricted with phenylephrine to 50% of their maximum and relaxed to increasing concentrations of methacholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368342 TI - Thyroid hormone stimulates the Na(+)-PO4 symporter but not the Na(+)-SO4 symporter in renal brush border. AB - In our previous studies we established that thyroid hormones [L-thyroxine (T4) or 3,5,3'-triiodothyronine (T3)] elicit an increase in Na(+)-Pi symport in rat and mouse renal brush-border membrane (BBM) vesicles (BBMV), but the Na(+)-coupled symports of other solutes were not influenced. However, a recent report [H. S. Tenenhouse, J. Lee, and N. Harvey. Am. J. Physiol. 261 (Renal Fluid Electrolyte Physiol. 30): F420-F426, 1991]claimed that T3 increases to a similar degree both Na(+)-Pi symport and Na(+)-SO4 symport in murine renal BBM. Adult male rats were fed either normal (0.7% Pi; NPD) or high-phosphate (1.4% Pi; HPD) diet and received T3 (0.2 mg/100 g body wt ip) for 3 days before the kidneys were removed, BBMV were prepared, and the transport rates were determined. Although the Na(+) Pi symport significantly increased (delta = +35%) in both NPD and HPD rats treated with T3, the Na(+)-35SO4 symport and Na(+)-D-[3H]glucose symports were not influenced by T3. Furthermore, treatment of NPD-fed mice with T3 using a similar protocol as rats resulted in a significant increase (delta = +26%) of Na(+)-(Pi)4 symport, but did not alter Na(+)-SO4 symport or Na(+)-glucose symport. Our findings thus document that T3 regulates selectively the Na(+)-Pi symporter in BBM without having any effect on other major divalent anions, such as SO4. PMID- 8368343 TI - Immunolocalization of the Na+/Ca2+ exchanger in rabbit kidney. AB - We recently isolated a cDNA encoding a Na+/Ca2+ exchanger from rabbit kidney that was highly similar to the canine cardiac sarcolemmal Na+/Ca2+ exchanger. In the present study, we used two different antibodies to the exchanger to identify the protein and establish its cellular and subcellular localization in the kidney. The first antibody was prepared against a fusion protein consisting of 190 amino acids of the large, presumably intracellular loop of the rabbit renal exchanger fused to the maltose-binding protein. The second was a monoclonal antibody generated against the isolated purified canine cardiac sarcolemmal exchanger. To identify the Na+/Ca2+ exchanger protein, we performed immunoblot analysis against a membrane vesicle preparation from rabbit kidney cortex. Both antibodies immunoblotted proteins of 120 and 70 kDa that are known to be associated with the exchanger. Indirect immunofluorescence revealed that both antisera labeled the basolateral surface of the majority of cells in the connecting tubule (CNT). Since the phase-dense (intercalated) cells in the CNT were not stained, this suggested that the labeled cells were CNT cells. No labeling was detected in other nephron segments with the exception of occasional faint staining of the majority cell population of the cortical collecting duct. The fact that we did not detect labeling in other nephron segments is consistent with either 1) the absence of expression of the Na+/Ca2+ exchanger in these segments, 2) the expression of the exchanger in levels below the threshold of detection of the two antibodies used in this study, or 3) the exchanger in these segments is represented by a different isoform.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368344 TI - Glucose use in neonatal rabbit hearts reperfused after global ischemia. AB - In this study, we measured both glycolysis and glucose oxidation during reperfusion of previously ischemic hearts obtained from 7-day and 6-wk-old rabbits. Isolated working hearts perfused with 11 mM [3H/14C]glucose, 0.4 mM palmitate, 0.5 mM lactate, and 100 microU/ml insulin were subjected to either 30 or 40 min of global ischemia followed by a 60-min period of reperfusion. Recovery of mechanical function was 58% in 7-day-old hearts subjected to 40 min of ischemia. In 6-wk-old rabbits, a 45% recovery of function was seen after only 30 min of ischemia. Addition of 1 mM dichloroacetate (DCA) to the perfusate at reperfusion increased glucose oxidation rates during reperfusion in both 7-day and 6-wk-old hearts (from 102 +/- 22 to 262 +/- 27 and from 280 +/- 63 to 523 +/- 97 nmol.min-1.g dry wt-1, respectively). Addition of DCA, however, resulted in a significant improvement in recovery of mechanical function only in 6-wk-old hearts (from 45 to 67% of preischemic function). These results demonstrate that fatty acid-perfused neonatal rabbit hearts are more able to tolerate ischemia than the matured rabbit hearts. However, our data suggest that there may be less potential to improve mechanical recovery in neonatal hearts during the actual reperfusion period by stimulating glucose oxidation. PMID- 8368345 TI - Collagen characterization in volume-overload- and pressure-overload-induced cardiac hypertrophy in minipigs. AB - Previous studies in several different species have shown reduced extractability of collagens in some types of cardiac hypertrophy (volume overload) but not others (pressure overload). The objective of the present study was to examine collagen proteins from the same species (minipigs) with both pressure-overload- and volume-overload-induced cardiac hypertrophy. Hypertrophy was induced by two methods: thoracic banding of the aorta to create pressure overload and arteriovenous shunt to cause volume overload in a porcine model. Collagen types I, III, IV, and V were isolated by pepsin digestion from normal and hypertrophied pig left ventricle tissues. Types I and III collagens from normal and hypertrophied samples, when separated from types IV and V, were digested with cyanogen bromide (CB), and the peptides were examined. Collagen concentration was increased in myocardium removed from hearts subjected to volume overload and unchanged in hearts subjected to pressure overload. The extractability of total collagen was unaffected in pressure-overloaded left ventricles but lower in samples from volume-overloaded hearts. CB digestion cleaved all of the types I and III collagens into similar smaller CB peptides with the exception of a 100 kDa peptide that was observed in both control and hypertrophied hearts. This peptide corresponds to one of the high-molecular-weight peptides found in canine heart tissue. The mature collagen cross-link hydroxylysylpyridinoline (HP) was identified in normal and hypertrophied types I and III collagen from porcine sources. Pressure-overload- and volume-overload-induced cardiac hypertrophy in the pig produced different alterations in the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368346 TI - Spatial features of calcium transients during early and delayed afterdepolarizations. AB - Although changes in intracellular Ca2+ concentration ([Ca2+]i) are spatially heterogeneous during spontaneous contraction in mammalian cardiac muscle, it has not yet been observed how [Ca2+]i changes spatially within cardiac myocytes during delayed (DADs) and early (EADs) afterdepolarizations. The aim of this study is to characterize the spatial features of the increase in [Ca2+]i during such afterdepolarizations and to understand the ionic mechanisms responsible for them. Myocytes were enzymatically isolated from guinea pig ventricles and loaded with fura 2-acetoxymethylester, the Ca2+ fluorescence indicator dye. Membrane potential was recorded with a conventional microelectrode technique, and spatiotemporal changes in fura 2 fluorescence and cell length were recorded using a digital television system. After superfusion with potassium-free Tyrode solution, DADs and EADs were induced. During DADs, fluorescence transients were heterogeneous within myocytes (n = 11). Furthermore, they often propagated within myocytes as if they were "waves." In contrast, during EADs, fluorescence transients showed no waves within myocytes but rather showed synchronous changes throughout the myocytes (n = 15). The results of this study suggest that the spatial features of the increase in [Ca2+]i differ between the DADs and EADs. We concluded from these differing features that the ionic mechanisms responsible for the two triggered activities are different. PMID- 8368347 TI - A method of determining electrical potential gradient across mitochondrial membrane in perfused rat hearts. AB - The electrical potential gradient across the mitochondrial membrane (delta psi m) in perfused rat hearts was estimated by calculating the equilibrium distribution of the lipophilic cation tetraphenylphosphonium (TPP+), using measured kinetic constants of uptake and release of TPP+. First-order rate constants of TPP+ uptake were measured during 30-min perfusions of intact rat hearts with tracer amounts (5.0 nM) of tritium-labeled TPP+ ([3H]TPP+) in the perfusate. This was followed by a 30-min washout, during which the first-order rate constant of efflux was estimated. Values of [3H]TPP+ outside the heart and total [3H]TPP+ inside the heart at equilibrium were calculated. From this information and separately estimated time-averaged plasma membrane potentials (delta psi c) it was possible to calculate free cytosolic [3H]TPP+ at equilibrium. It was also possible to calculate free intramitochondrial [3H]TPP+ at equilibrium as the difference between total tissue [3H]TPP+ minus free cytosolic TPP+ and the sum of all the bound [3H]TPP+. Bound [3H]TPP+ was determined from [3H]TPP+ binding constants measured in separate experiments, using both isolated mitochondria and isolated cardiac myocytes under conditions where both delta psi m and delta psi c were zero. Delta psi m was calculated from the intramitochondrial and cytosolic free TPP+ concentrations using the Nernst equation. Values of delta psi m were 144.9 +/- 2.0 mV in hearts perfused with 5 mM pyruvate and 118.2 +/- 1.4 mV in hearts perfused with 11 mM glucose, in good agreement with delta psi m obtained from isolated rat heart mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368348 TI - Effects of cardiac work on electrical potential gradient across mitochondrial membrane in perfused rat hearts. AB - The myocardium responds to alterations in cardiac work by changing its rate of O2 consumption. This reflects an increase in the oxidative synthesis of ATP to meet the contractile demand for ATP. However, the biochemical mechanisms responsible for increased ATP synthesis are not fully understood. To localize the flux controlling reaction(s) in the pathway of ATP synthesis, the effects of substrates and cardiac work on mitochondrial membrane potential (delta psi m), total tissue NADH-to-NAD+ ratio, and high-energy phosphate metabolites were examined in perfused rat hearts. Delta psi m was measured using the equilibrium distribution of tetraphenylphosphonium (33). Cytosolic phosphorylation potential, total tissue NADH-to-NAD+ ratio, and delta psi m were higher in hearts perfused with pyruvate than in those perfused with glucose. Increasing cardiac work induced a four-fold increase in O2 consumption, which was accompanied by 1) decreased or unaltered cytosolic ADP concentration, 2) increased tissue NADH-to NAD+ ratio, and 3) decreased delta psi m. The results indicate that both NADH generating reactions and the ATP synthase-catalyzed reaction are important in causing the increase in respiration that accompanies increased work. Because the activation of ATP synthase by cardiac work occurred in the absence of increases in delta psi m, ADP, and Pi, it is possible that the work-related acceleration in ATP synthesis may be due to modification of the kinetic properties of the ATP synthase. PMID- 8368349 TI - Sarcolemmal phospholipid asymmetry and Ca fluxes on metabolic inhibition of neonatal rat heart cells. AB - The present study examines the hypothesis that during depletion of high-energy phosphates a change will occur in the phospholipid topology and in Ca fluxes in cultured neonatal cells and that these two events may be causally related. A combination of 2-deoxyglucose and iodoacetic acid was used to produce graded changes in the adenine nucleotides in the cells. An on-line technique for 45Ca measurement was used to follow Ca uptake and compartmentation by the cells, and chemical and enzymatic probes were used to study sarcolemmal phospholipid topology. After 15 min of metabolic inhibition (ATP = 10% of control) an increase in cellular Ca occurs, which progresses with time. Over 70% of this Ca accumulates in the mitochondria. After 30 min of metabolic inhibition (ATP < 10% of control) a change in the phospholipid topology is observed, and an increased amount (two times control) of sarcolemmal phosphatidylethanolamine is present in the outer monolayer of the sarcolemma. This change in phospholipid topology was independent of the extracellular Ca concentration. The sequence of altered Ca fluxes and distribution followed by the altered phospholipid topology is discussed in terms of its possible role in the pathogenesis of sarcolemmal disruption. PMID- 8368350 TI - Biaxial mechanical properties of passive and tetanized canine diaphragm. AB - The architecture, vascular supply, and ease of tetanization make the diaphragm an ideal structure in which to assess multidimensional mechanical properties of active and passive striated muscle. We developed an isolated, perfused canine diaphragm preparation suitable for the assessment of biaxial stress-strain relations in both the resting state and during tetanization. Each of 33 specimens had a wide, flat region (approximately 3 x 3 cm) wherein there was a single predominant fiber direction. Simultaneous, equal stretchings were imposed in the fiber and perpendicular cross-fiber directions over the same strain ranges in both the passive state and during tetanic contraction. Highly nonlinear behavior was seen in the passive state with a limit of extensibility in both directions. The specimens were also markedly anisotropic, with the cross-fiber direction being stiffer than the fiber direction (slopes of the regression line for the stresses in each direction averaged 3.97). Moreover, 31 of the 33 specimens were stiffer in the cross-fiber direction, one was isotropic, and one was stiffer in the fiber direction. During tetanization, the extent and distribution of anisotropy were significantly altered (regression slope averaged 1.08, and 18 specimens were now either isotropic or stiffer in the fiber direction). Disrupting the membranes covering each surface increased extensibility and decreased the anisotropy, thereby suggesting that these membranes bear most of the passive load and contribute greatly to the cross-fiber stiffness and anisotropy of the intact diaphragm. Both before and after disruption of the surface membranes, there was still a consistent increase in cross-fiber stress during tetanization, implying active force generation perpendicular to the fiber direction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368351 TI - Stimulated leukocyte adhesion in coronary microcirculation is reduced by a calcium antagonist. AB - The first step in the acute myocardial inflammatory response is leukocyte sequestration in the coronary microcirculation. To determine the location(s) of stimulated leukocyte deposition in the coronary microcirculation and the effects of the calcium antagonist, nisoldipine, on leukocyte adhesion, leukocytes were stimulated with the chemotactic peptide, N-formylmethionyl-leucyl-phenylalanine (FMLP) and blood cell adherence was evaluated using two methods. In vitro leukostasis was evaluated by measuring the extraction of white cells in nylon fiber columns. We found that diluted whole blood (DWB) demonstrated 30% granulocyte adherence. The chemotactic peptide FMLP (1 microM) significantly increased adherence to 69%. Pretreatment of the blood with nisoldipine (1 microM) immediately before FMLP significantly reduced the FMLP-induced adhesion to 47%. In the coronary microcirculation, FMLP caused a marked increase in leukocyte sequestration, primarily in coronary capillaries. The FMLP effect was somewhat transient because the washout of trapped white cells was similar in the vehicle and FMLP groups. Nisoldipine significantly reduced the FMLP-induced leukostasis in coronary capillaries (P < 0.05). The magnitude of the attenuation of leukostasis with nisoldipine was remarkably similar in both models, suggesting a direct effect of this agent on the blood rather than on the blood vessels. These findings offer another possible mechanism by which dihydropyridine calcium antagonists may be cardioprotective under pathophysiological conditions. PMID- 8368352 TI - Increase in endogenous antioxidant enzymes protects hearts against reperfusion injury. AB - Coarctation of the abdominal aorta in rats for 10 wk increased the heart weight to-body weight ratio by 36% and peak left ventricular systolic pressure by 75%; there was no apparent change in the end-diastolic pressure, and animals did not show any clinical signs of heart failure. These hypertrophied (H) hearts showed increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) with no change in catalase. Lipid peroxide content as indicated by the malondialdehyde (MDA) level was lower in H hearts. There was no apparent difference in either Na+ and Ca2+ content or high-energy phosphates between sham (S) and H hearts. Control and H hearts were subjected to 10 min of ischemia (I) and 15 min of reperfusion (R). Contractile failure and rise in resting tension due to I, in both S and H hearts, were comparable. On reperfusion, H hearts showed better recovery of the developed force and resting tension as well as reduced incidence of arrhythmias when compared with corresponding S hearts. Both SOD and GSHPx activities were depressed due to I-R, but these activities were significantly higher in reperfused H hearts. Reperfused H hearts also showed a better maintenance of the ultrastructure and Na+ and Ca2+ contents, recovery of high-energy phosphates, and reduced MDA levels compared with S hearts. Supplementation of the perfusion medium with SOD (120 U/ml) and catalase (80 U/ml) significantly attenuated the I-R injury in S hearts, and the response in many ways was comparable to H hearts. The study documents the therapeutic potential of increased myocardial endogenous antioxidants against oxidative stress. PMID- 8368353 TI - Effect of adenosine receptor blockade: preventing protective preconditioning depends on time of initiation. AB - Ischemic preconditioning protects the rabbit myocardium from infarction from a subsequent ischemia, and adenosine receptors appear to be involved in this protection. The present study attempts to determine when adenosine receptors must be occupied to achieve protection by infusing the adenosine receptor antagonist PD-115,199 at various time points during the study. Open-chest rabbits were subjected to 30 min of regional ischemia followed by 3 h of reperfusion and had 38 +/- 4% infarction of the risk zone. When hearts were preconditioned by 5 min of ischemia and 10 min reperfusion before the 30-min period of ischemia, only 9 +/- 2% infarction occurred. PD-115,199 given 5 min before the ischemic preconditioning episode blocked the protective effect of preconditioning (39 +/- 5% infarction). PD-115,199 also blocked the protection when given between the ischemic preconditioning episode and the 30-min period of ischemia (30 +/- 4% infarction). PD-115,199 given at the end of 30 min of ischemia did not block protection in preconditioned (PC) hearts (17 +/- 5% infarction) and had no effect on non-PC hearts (44 +/- 6% infarction). In prior studies we found that exogenous adenosine could substitute for ischemia to precondition the heart, indicating that adenosine is an initiator of preconditioning. These results, however, indicate that adenosine receptors must also be occupied during the long ischemic period for preconditioning to be protective and suggest that adenosine is a mediator of preconditioning as well. PMID- 8368354 TI - Age-related changes in endothelium-dependent hyperpolarization in the rat mesenteric artery. AB - This study was designed to determine the age-related changes in the endothelium dependent hyperpolarization to acetylcholine (ACh) and its contribution to relaxation in the isolated mesenteric artery from normotensive and hypertensive rats. Membrane potentials and contractions were recorded in arteries from male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) that were 5-6 wk old (young), 6-8 mo old (adult), and 20-26 mo old (aged). Endothelium dependent hyperpolarizations produced by ACh, applied both at the resting state of the membrane and under conditions of depolarization with norepinephrine (10( 5) M), were markedly impaired in aged WKY rats, adult SHR, and aged SHR. Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10( 5) M norepinephrine were also impaired in aged WKY rats, adult SHR, and aged SHR even in the presence of indomethacin. Furthermore, in these rats, N omega-nitro-L arginine, an inhibitor of nitric oxide formation, showed potent inhibitory effects on the relaxations, whereas the 20 mM high K+ solution that reduces hyperpolarization had less pronounced effects. Hyperpolarizations and relaxations to cromakalim (10(-5) M), a K(+)-channel opener, were on the whole preserved in aged rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced with aging as well as by hypertension, and this would, in part, account for the impaired relaxation to ACh in arteries of both aged rats and hypertensive rats. PMID- 8368355 TI - Thapsigargin inhibits Ca2+ uptake, and Ca2+ depletes sarcoplasmic reticulum in intact cardiac myocytes. AB - We examined the effects of thapsigargin on Ca2+ accumulation by the sarcoplasmic reticulum (SR) and on electrically stimulated beats in single adult rat ventricular myocytes loaded with indo 1 and bathed in N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid buffer containing 1 mM Ca2+ at 23 degrees C. The SR Ca2+ content was assessed from the magnitude of intracellular Ca2+ (Ca2+i) transients and contractions elicited by rapid, brief applications of caffeine. After 20-30 min of exposure to 200 nM thapsigargin, the caffeine-dependent Ca2+i transients were abolished or markedly diminished (by 89 +/- 4%). The postrest potentiation of the Ca2+i transient and contraction, typical for rat myocardium, was abolished. Thapsigargin did not significantly change resting Ca2+i but diminished the amplitude of the steady-state Ca2+i transients by 73%, prolonged the time to peak by 24%, and prolonged the half-time (t1/2) of the Ca2+i transient decline by 42%. Progressive SR Ca2+ depletion by thapsigargin was strongly related (r = 0.78) to the prolongation of the t1/2 of relaxation of the steady-state Ca2+i transients, suggesting that the thapsigargin-dependent SR Ca2+ depletion results from an inhibition of the SR Ca2+ uptake. This interpretation was corroborated by comparison of the effects of thapsigargin with those of ryanodine (100 nM), which depletes SR of Ca2+ by accelerating the SR Ca2+ efflux but does not inhibit the SR Ca2+ pump. During rapid pacing (5 Hz), which raises Ca2+i and thus Ca2+ available for SR uptake, the caffeine-dependent SR Ca2+ release was restored in ryanodine-treated cells but not in the presence of thapsigargin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368356 TI - Influence of endothelial surface on flow velocity in vitro. AB - The influence of the endothelial surface and its interaction with various plasma components on flow velocity was investigated in vitro. The falling velocity of microcarrier beads with and without cultured porcine aortic endothelial cells in a vertical tube containing different media was recorded with a video system attached to a light microscope. The falling velocity of the beads was in agreement with values predicted from Stokes's law. Endothelium did not affect the falling velocity in various media, except in plasma, where it was slower than expected. Fibrinogen was found to have a strong surface tension effect, disturbing viscosity measurements, and to bind to endothelial cells and collagen coated surfaces. We conclude that the endothelial surface may interact with plasma and plasma constituents such as fibrinogen in a way that affects blood flow. PMID- 8368357 TI - Relationship between capillary and systemic venous PO2 during nonhypoxic and hypoxic ventilation. AB - We evaluated the relationship between end-capillary and systemic venous PO2 values in the retractor muscle of 14 anesthetized hamsters during both nonhypoxic and hypoxic ventilation to ascertain whether the level of tissue oxygenation could be reliably estimated from the systemic parameter. End-capillary PO2 was estimated from measurements of oxygen saturation in capillaries at the venular end of the network obtained using in vivo video microscopy and computer-aided image-analysis techniques at three different levels of inspired oxygen (0.3, 0.21, and 0.1). Measurements of systemic arterial and venous blood gases were made in conjunction with these capillary determinations. In addition, in a portion of the study we utilized an oxygen microelectrode to determine the PO2 in the first-order venule draining the portion of the muscle containing the capillaries under study. We found that only when the animals were made acutely hypoxic was there any correspondence between the systemic venous and end capillary PO2 values. In addition, these data provide support for the presence of arteriovenous shunting of oxygen during nonhypoxic ventilation. PMID- 8368358 TI - Permeability to albumin in isolated coronary venules. AB - This study reports measurements of albumin permeability in isolated coronary venules. The isolated microvessel technique allows the quantification of transmural exchange of macromolecules under tightly controlled physical and chemical conditions. Transvenular exchange of albumin was studied in isolated coronary venules during alterations in filtration rate caused by changes in intravascular pressure. The apparent permeability coefficient of albumin (Pa) at an intraluminal pressure of 11 cmH2O was 3.92 +/- 0.43 x 10(-6) cm/s. Elevating intraluminal pressure to 16 and 21 cmH2O increased Pa to 5.13 +/- 0.57 x 10(-6) and 6.78 +/- 0.66 x 10(-6) cm/s, respectively. Calculation of the true diffusive permeability coefficient of albumin (Pd) at zero filtration rate was 1.54 x 10( 6) cm/s. The product of hydraulic conductance (Lp) and (1 - sigma), where sigma is the solute reflection coefficient, was 3.25 x 10(-7) cm.s-1 x cmH2O-1. At a net filtration pressure of 4-5 cmH2O, diffusion accounts for > 60% of total albumin transport across the venular wall. Transmural albumin flux is very sensitive to filtration rate, rising 6.7% for each cmH2O elevation of net filtration pressure. At 11 cmH2O net filtration pressure, convection accounts for nearly 70% of net albumin extravasation from the venular lumen. We suggest that the isolated coronary venule is a suitable preparation for the study of solute exchange in the heart. PMID- 8368359 TI - Time-dependent rheological behavior of blood at low shear in narrow vertical tubes. AB - The time-dependent flow behavior of normal human blood after a sudden reduction of wall shear stress from 5,000 mPa to a low level (2-100 mPa) was studied during perfusion of vertical tubes (internal diam 28-101 microns) at constant driving pressures. Immediately after the implementation of low-shear flow conditions the concentration of red blood cells (RBCs) near the tube wall started to decrease, and marginal plasma spaces developed as a result of the assembly of RBC aggregates. This was associated with a time-dependent increase of flow velocity by up to 200% within 300 s, reflecting a reduction of apparent viscosity. These time-dependent changes of flow behavior increased strongly with decreasing wall shear stress and with increasing tube diameter. A correlation between the width of the marginal plasma layer and relative apparent viscosity was obtained for every condition of tube diameter, wall shear stress, and time. Time-dependent changes of blood rheological properties could be relevant in the circulation, where the blood is exposed to rapid and repeated transitions from high-shear flow conditions in the arterial and capillary system to low-shear conditions in the venous system. PMID- 8368360 TI - Mechanisms of control of skin blood flow during prolonged exercise in humans. AB - Exercise in a warm environment raises internal temperature and leads to a rapid increase in skin blood flow (SkBF). As exercise continues, and internal temperature approaches 38 degrees C, the rate of rise of SkBF is markedly attenuated despite further significant increases in internal temperature. To find whether this attenuation is mediated by increased cutaneous active vasoconstrictor activity or by a reduced rate of rise of active vasodilator activity, each of 12 male subjects had 0.64 cm2 forearm skin sites iontophoretically treated with bretylium tosylate for selective local blockade of noradrenergic vasoconstrictor nerves. SkBF was monitored there and at adjacent untreated control sites by laser-Doppler blood flowmetry (LDF). Whole body skin temperature (Tsk) was controlled by water-perfused suits, and esophageal temperature (Tes) was monitored as an index of internal temperature. Mean arterial pressure (MAP) was monitored and cutaneous vascular conductance was calculated as LDF/MAP. Sweat rate was also monitored by dew point hygrometry in 11 subjects. Tsk was raised to 38 degrees C, after which subjects began 20-30 min of exercise on a bicycle ergometer. The rate of the initial rapid increase in SkBF with increasing Tes was not altered by bretylium treatment (P > 0.05 between sites). The attenuation of the rate of rise during the latter phase of exercise was not abolished by bretylium treatment (P > 0.05 between sites); instead, there was a trend for the attenuation to be enhanced at those sites. We conclude that the attenuated rate of rise of SkBF is due to limitation of active vasodilator activity and not due to increased vasoconstrictor tone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368362 TI - Vascular endothelial growth factor induces EDRF-dependent relaxation in coronary arteries. AB - Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), has recently been shown to increase cytosolic free calcium in endothelial cells. In the present study, we investigated the coronary vascular effects of recombinant human and native guinea pig VEGF/VPF in isolated canine coronary arteries in the presence and absence of intimal endothelium, indomethacin, and NG-monomethyl-L-arginine, a competitive nitric oxide synthase inhibitor. Addition of recombinant VEGF/VPF (1-660 pM) in coronary arteries that had been previously contracted with prostaglandin F2 alpha induced a slow, dose dependent relaxation, reaching a maximum of -59.1 +/- 6.7% (mean +/- SE, n = 19). Mechanical disruption of the intimal endothelium completely abolished the observed relaxation. No direct vascular effect of recombinant VEGF/VPF on the endothelium-disrupted coronary arteries was noted. Pretreatment of endothelium intact coronary arteries with 5 microM of indomethacin did not alter the observed relaxation (-57.3 +/- 7.0%, n = 18), whereas pretreatment with either NG monomethyl-L-arginine or 10 microM of genistein, a known inhibitor of tyrosine kinase, significantly inhibited the relaxation. Addition of native VEGF/VPF (1 100 pM) also induced an endothelium-dependent relaxation in the isolated coronary arteries. Heating of recombinant VEGF/VPF (70 degrees C, 25 min) or prior incubation with a specific antibody raised against a VEGF/VPF peptide completely abolished the relaxation. Finally, recombinant VEGF/VPF stimulated a slow rise in cytosolic free calcium in cultured human endothelial cells that was qualitatively similar to that of native VEGF/VPF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368361 TI - Role of ATP-sensitive K+ channels in CGRP-induced dilatation of basilar artery in vivo. AB - Stimulation of adenylate cyclase appears to activate ATP-sensitive K+ channels in the basilar artery. We tested the hypothesis that calcitonin gene-related peptide (CGRP), which increases intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels, activates ATP-sensitive K+ channels and thereby causes vasodilatation. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to CGRP in vivo. We also examined responses of the artery to another vasoactive peptide, vasoactive intestinal peptide (VIP). Topical application of CGRP (10(-11) to 10(-8) M) increased diameter of the basilar artery. Responses of the basilar artery to CGRP were almost abolished by a CGRP1 receptor antagonist, CGRP-(8-37). Vasodilatation in response to VIP was much smaller than that produced by CGRP. Dilator responses of the basilar artery to 10(-9) and 10(-8) M CGRP were inhibited by glibenclamide (10(-6) M), a selective inhibitor of ATP sensitive K+ channels, by 69 +/- 19 and 41 +/- 9%, respectively. NG-nitro-L arginine methyl ester (10(-5) M), an inhibitor of nitric oxide synthase, did not attenuate dilator response to 10(-8) M CGRP but inhibited responses to 10(-9) M CGRP by 34 +/- 12%. Indomethacin did not alter dilator responses to CGRP. These findings suggest that a minor component of CGRP-induced dilatation of the basilar artery is mediated by endothelium-derived relaxing factor. Vasodilatation in response to CGRP appears to be mediated primarily by direct activation of CGRP1 receptors on vascular muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368363 TI - Repletion of sarcoplasmic reticulum Ca after ryanodine in rat ventricular myocytes. AB - The ryanodine (R)-induced loss of sarcoplasmic reticulum (SR) Ca2+ and the abilities of the SR to accumulate Ca2+ and participate in contractile activation after R were studied in rat ventricular myocytes. Indo 1 fluorescence (IF) indexed cytosolic Ca2+, and caffeine assayed SR Ca2+. Before R, there was a negative staircase, and the SR accumulated Ca2+ at rest. During stimulation (0.5 Hz), R decreased IF and contraction, converting the negative staircase to positive. When R was pulsed onto resting cells, IF increased and cells shortened, subsequently behaving as if stimulated in R. After R, there was no caffeine releasable Ca2+ at rest, and little accumulated during 0.5-Hz stimulation. At high rates, caffeine-releasable Ca2+ and diastolic IF increased. In isoproterenol and R, IF transients and contractions recovered at 0.5 Hz with a marked positive staircase and little diastolic IF increase. Within 10 beats, SR Ca2+ accumulated to pre-R levels. R eliminated the positive inotropic effect of paired-pulse stimulation, but isoproterenol temporarily restored it. Twitch contractions in thapsigargin, an SR Ca2+ pump blocker, and isoproterenol were slow compared with control or R + isoproterenol. R leaks SR Ca2+ into the cytosol. SR Ca2+ can be repleted in R by high-rate stimulation or by low-rate stimulation with a beta adrenergic agonist. SR Ca2+ release in R can be temporarily restored if Ca2+ influx and SR Ca2+ pumping are increased enough to overcome the SR Ca2+ leak. PMID- 8368364 TI - Arterial compliance and its control by the baroreflex in hypertensive dogs. AB - The effect of the carotid baroreflex on systemic arterial compliance was tested in normotensive and Goldblatt hypertensive dogs. After the development of experimental hypertension, dogs were acutely anesthetized with pentobarbital sodium and vagotomized. The carotid sinuses were then isolated and held at controlled carotid sinus pressures (CSP) of 50, 125, and 200 mmHg. The dogs were placed on constant flow, constant venous pressure, cardiopulmonary bypass. Arterial compliance was determined from the time constant of the exponential fall in arterial pressure, which occurred when the flow was stopped at three different levels of CSP. The reflex characteristic curve (mean arterial pressure vs. CSP) was shifted upward and to the right in the hypertensive group. Arterial compliance significantly decreased with decreasing CSP, but at any given level of CSP, arterial compliance was not different in the normotensive and hypertensive groups. A nonlinear analysis revealed that the arterial compliance-arterial pressure relationship was not altered by Goldblatt experimental hypertension. The results of this study indicate that the arterial compliance is primarily a function of the absolute level of arterial pressure. Baroreflex control of arterial compliance is important at lower levels of arterial pressure. PMID- 8368365 TI - Regional blood flow in canine atria during exercise. AB - Global and regional atrial blood flow was measured with radioisotope-labeled microspheres in eight dogs during rest and two levels of exercise. Both mean right and left atrial blood flow increased significantly (P < 0.05) to a similar degree with each level of exercise (right atria: 0.27 +/- 0.04, 0.89 +/- 0.11, and 1.57 +/- 0.21 ml.min-1 x g-1; left atria: 0.35 +/- 0.04, 0.90 +/- 0.09, and 1.61 +/- 0.17 ml.min-1 x g-1). Atrial blood flow during exercise is greater than anticipated if increased heart rate was the sole cause. In both right and left atria the ratio of appendage to nonappendage flow was significantly (P < 0.005) less than one during resting conditions (0.42 +/- 0.04 and 0.81 +/- 0.05, respectively), not different from unity during mild exercise, and significantly (P < 0.02) greater than one during moderate exercise (1.10 +/- 0.03 and 1.16 +/- 0.05, respectively). This disparity in the blood flow to the appendage and nonappendage regions suggests that the appendage plays an augmented hemodynamic role during exercise, thus requiring a larger proportion of the nutrient flow. PMID- 8368366 TI - Cardiac effects of injections of epinephrine into the spinal intermediolateral column. AB - Small doses of epinephrine (0.008, 0.05, and 0.1 pmol, i.e., 20-nl volumes of 0.40, 2.5, and 5 microM solutions) produced a dose-dependent increase in heart rate when micro-injected into the right intermediolateral column (IML) at T2 spinal level. These effects were mediated via alpha 1-adrenergic receptors because prazosin blocked them. The presence of alpha 1-adrenergic receptors at this site was confirmed by microinjections of phenylephrine (a specific agonist for these receptors); phenylephrine elicited tachycardia. Larger doses of epinephrine (320, 2,000, and 3,200 pmol, i.e., 20-nl volumes of 16, 100, and 160 mM solutions) caused bradycardia when microinjected into the IML. These effects were mediated via alpha 2-adrenergic receptors because idazoxan blocked them. The presence of alpha 2-adrenergic receptors at this site was confirmed by microinjections of clonidine (a specific agonist for these receptors); clonidine elicited bradycardia. Injections of the vehicle (20 nl of normal saline containing 0.3% ascorbic acid, pH 7.4) did not evoke a response. Epinephrine, prazosin, or idazoxan did not alter the responses to L-glutamate. None of the doses of epinephrine elicited any response when injected intravenously. The aforementioned results provide pharmacological evidence for the presence of alpha 1- and alpha 2-adrenergic receptors in the IML at T2. Thus a basis is provided for investigating the role, if any, of alpha-adrenergic receptors in the IML in mediating cardiovascular responses elicited by the stimulation of different brain stem areas. PMID- 8368367 TI - Control of resting bronchial hemodynamics in the awake dog. AB - In the resting awake dog a continuous-wave Doppler flow transducer on the right bronchoesophageal artery inscribes a sharp early systolic spike and low flow in late systole and throughout diastole, indicating a highly resistive bed. An analysis of autonomic factors using intravenous, cumulative, and randomly applied cholinoceptor, beta 1- and beta 2-adrenoceptor, and alpha 1- and alpha 2 adrenoceptor antagonists indicates that the low vascular conductance is due to cholinoceptor and alpha 1- and alpha 2-adrenoceptor effects in a ratio 3.6:1. No beta-adrenoceptor tone is present. Sighing behavior invokes a transient (< 2 s) fall in intrapleural pressure (and thus rise in bronchovascular transmural pressure) of 10-30 mmHg, which is followed by a two- to threefold increase over 30 s in bronchial flow and conductance, an effect simulated in 50% of dogs when bronchovascular transmural pressure is acutely raised and maintained over 40-60 s by inflating an intra-aortic balloon distal to the origin of the bronchial artery. Autonomic blockade has no effect on bronchovascular dilatation evoked either by sighing or by balloon inflation. It is concluded that, in the resting bronchial circulation, there exists strong cholinoceptor and alpha-adrenoceptor based vasoconstrictor activity which can be overpowered by strong nonadrenergic noncholinergic local vasodilator reflexes evoked by sudden changes in intrathoracic transmural pressure possibly acting on stretch-sensitive sensory nerve endings containing substance P, calcitonin gene-related peptide, and neurokinins. The tonic vasoconstrictor but not the sigh-evoked vasodilator effects are sensitive to pentobarbital sodium anesthesia. PMID- 8368368 TI - Neuropeptide Y potentiates contractile response to norepinephrine in skate coronary artery. AB - The skate is an extant representative of the first vertebrate group with a coronary circulation, the elasmobranch fish. Histochemical studies have revealed that skate coronary arteries are innervated by adrenergic nerves as well as by nerves showing neuropeptide Y (NPY)-like immunoreactivity. This study investigates the effect of NPY in the coronary system of an elasmobranch fish, a vertebrate that first evolved 450 million years before mammals and the mammalian coronary circulation. The responses of vascular ring preparations of the coronary artery from the longnose skate (Raja rhina) were measured using isometric force transducers. The main effect of NPY was a potentiation of the amplitude of the norepinephrine-induced contraction, leaving the pD2 value (-log 50% effective concentration) for norepinephrine unaffected. NPY per se occasionally contracted the coronary rings in higher concentrations. The potentiation response may not involve the endothelium and was abolished by pretreatment with tetrodotoxin. We conclude from this study that NPY potentiates norepinephrine-induced contraction in skate coronary artery via an indirect pathway. PMID- 8368369 TI - Electrically stimulated contraction accelerates protein synthesis rates in adult feline cardiocytes. AB - Cardiocytes were induced to contract via electrical field stimulation with an 8 V/cm electrical square-wave pulse of 5 ms at 0.125-2.0 Hz for up to 6 h. Protein synthesis rates were measured as rate of incorporation of [3H]-phenylalanine into total cell protein. Rates of protein synthesis were accelerated 43 +/- 4%, P < 0.001, by 4 h. The acceleration of total protein synthesis showed a frequency dependence between 0.125 and 0.5 Hz. In addition to accelerating rates of total protein synthesis, electrical stimulation of contraction accelerated fractional rates of synthesis of myosin heavy chain by 42 +/- 8%, P < 0.05. Protein synthesis rates were not accelerated upon electrical stimulation using subthreshold voltages. Addition of 100 ng/ml of actinomycin D had no effect on the ability of electrical stimulation of contraction to accelerate protein synthesis. To uncouple excitation-contraction coupling, 2,3-butanedione monoxime (BDM) was used to block actin-myosin cross-bridge interactions. BDM significantly decreased the ability of electrical stimulation to accelerate protein synthesis rates. PMID- 8368370 TI - Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in dogs. AB - To test the hypothesis that afferent traffic of the ATP-triggered vagal reflex travels mainly in the right vagus nerve, we quantitated the response of the sinus node pacemaker activity and atrioventricular (AV) nodal conduction to increasing doses of intra-atrial ATP under baseline conditions, in the presence of aminophylline, and subsequently after either right followed by left cervical vagotomy or vice versa. In addition, the effect of right vagal C-fiber afferent blockade on the action of ATP in the sinus node was also determined. Because vagal efferent traffic to the sinus and AV nodes travels mainly via the right and left vagus nerves, respectively, the working hypothesis predicted that left vagotomy would have a much smaller effect than right vagotomy on the negative chronotropic action of ATP in the sinus node and predicted similar effects of left vs. right vagotomy on the negative dromotropic action of ATP on AV nodal conduction. ATP suppressed sinus node automaticity and AV nodal conduction in a dose-dependent manner. The attenuation of the action of ATP on the sinus node by right vagotomy was much more pronounced than that caused by left vagotomy, while the negative dromotropic action of ATP in the AV node was similarly attenuated by right vs. left vagotomy. In addition, sinus node automaticity, which was only mildly attenuated by left vagotomy, was markedly suppressed by right vagal C fiber afferent blockade. It was concluded that in the dog, afferent vagal traffic triggered by intra-right atrial ATP travels under these experimental conditions mainly via the right vagus nerve. PMID- 8368371 TI - Preconditioning protects coronary arteriolar endothelium from ischemia reperfusion injury. AB - The objectives of this study were to test the hypotheses that 1) endothelium dependent regulation of coronary arteriolar reactivity is impaired after ischemia and reperfusion, and 2) preconditioning protects the arteriolar endothelium from reperfusion injury. In anesthetized open-chest dogs, coronary arteriolar diameters (30-110 microns) were measured in the beating heart using intravital microscopy during fluorescent stroboscopic epi-illumination in three groups: 1) control, 2) ischemia and reperfusion: 60-min occlusion and 120-min reperfusion of the left circumflex coronary artery, and 3) preconditioning: 10-min occlusion and reperfusion preceding ischemia-reperfusion. To evaluate endothelial reactivity, the diameter responses of coronary arterioles to the endothelium-dependent vasodilators, acetylcholine and serotonin, were assessed. Ischemia and reperfusion significantly reduced the increase in diameter by serotonin (0 +/- 2 vs. 11 +/- 3% change in controls; P < 0.05) and acetylcholine (7 +/- 2 vs. 20 +/- 2% in controls; P < 0.05). In contrast, preconditioning preserved the dilation to both serotonin (6 +/- 1%) and acetylcholine (24 +/- 3%; both NS vs. control; P < 0.05 vs. ischemia and reperfusion). Dilation by the endothelium-independent vasodilator, papaverine, was similar in the three groups, indicating similar levels of vasodilatory reserve and suggesting that the impaired dilation to acetylcholine and serotonin after ischemia and reperfusion was not due to nonspecific damage to vascular smooth muscle. These data demonstrate that ischemia-reperfusion significantly attenuates endothelium-dependent vasodilation of coronary arterioles in the intact beating heart. Furthermore, preconditioning reduces the endothelial dysfunction of coronary arterioles after ischemia reperfusion. PMID- 8368372 TI - Effects of hypertension and coronary constriction on cardiac function, morphology, and contractile proteins in rats. AB - In an attempt to elucidate the effects of two major risk factors of heart failure in humans, high blood pressure and coronary artery disease, renal hypertension and coronary artery constriction were induced singularly and in combination in rats, and the functional, structural, and biochemical alterations of the myocardium were examined 12-13 wk later. Renal hypertension (RH), coronary narrowing (CN), and their association (NH) resulted in left ventricular failure demonstrated by a significant increase in left ventricular end-diastolic pressure, a decrease in +dP/dt and -dP/dt, and a reduction in stroke volume and cardiac output. Measurements of ventricular loading documented that RH was characterized by elevations in systolic and diastolic wall stress of 42 and 160%, respectively. Corresponding changes with NH were 80 and 315%. CN was accompanied by an augmentation of diastolic wall stress only (280%). The abnormalities in mural stress were coupled with reductions in systolic and diastolic wall thickness-to-chamber radius ratios of 39 and 29% after CN. These anatomic parameters were preserved with RH, whereas the systolic wall thickness-to-chamber radius ratio was reduced 31% with NH. Structurally, multiple foci of replacement fibrosis were found with each intervention. The sites of tissue injury and their volume percent in the myocardium were comparable with CN and RH but were significantly more numerous and occupied a larger fraction of the ventricular wall in the presence of NH. Biochemically, the calcium dose-response curve of myofibrillar Mg2+ adenosinetriphosphatase (ATPase) activity did not vary with CN, RH, and NH. In contrast, a marked decrease in Ca2+ myosin ATPase activity was found in NH rats in association with a shift in myosin isoenzymes from V1 to V3. In conclusion, multiple physiological, morphological, and biochemical factors may participate in the generation of the abnormalities in ventricular loading with hypertension and/or coronary artery stenosis. PMID- 8368373 TI - Plasmalemmal vesicles represent the large pore system of continuous microvascular endothelium. AB - In the capillary physiology literature, molecules and particles larger than 10 nm are assumed to leave the plasma mostly through large pores located at the level of intercellular junctions in microvessels lined with a continuous endothelium. In morphological studies of similar microvessels, outgoing particles > 10 nm were detected in endothelial plasmalemmal vesicles not in intercellular junctions. Because the probes may not be found in transit through the junctions because they may be swept away by strong currents generated by Starling forces, we have examined a large number of junctions in arteriolar, capillary, and venular segments of bipolar vascular fields of mouse diaphragms collected after perfusion with large pore probes. The results presented in this study indicate that 1) the perfused probes accumulate in the luminal introits of the junctions as filtration residues that decrease in size and frequency from arterioles to venules, and 2) large pore probes move across the endothelium exclusively through plasmalemmal vesicles. PMID- 8368374 TI - Pertussis toxin-induced ADP ribosylation of inhibitor G proteins alters vagal control of heart rate in vivo. AB - Prior studies have shown that in vivo systemic administration of pertussis toxin in conscious dogs catalyzes ADP ribosylation of Gi and G(o) proteins, which attenuates intracellular transduction of muscarinic receptor activation. We tested the hypothesis that this impairment may result in the alteration of the following indexes of cardiac vagal activity: baroreflex sensitivity and heart rate variability. Heart rates during submaximal exercise were also determined. These variables were measured in eight conscious dogs before and 72 hr after pertussis toxin administration. Pertussis toxin significantly reduced (P < 0.001) baroreflex sensitivity (from 18.7 +/- 2.6 to 6.8 +/- 1.4 ms/mmHg), the SD of the mean R-R intervals (from 176 +/- 17 to 61 +/- 7 ms), the mean R-R interval (from 742 +/- 32 to 527 +/- 29 ms), and the coefficient of variance [from 235 +/- 15 to 114 +/- 1 (x 1,000)]. The heart rate response to graded submaximal exercise after pertussis toxin was higher (P < 0.001) at each exercise level. In in vitro assay, cardiac tissue samples from pertussis toxin-treated dogs incorporated 10-fold less ADP ribose than what has been described previously. These data prove that the in vivo action of pertussis toxin on cardiac inhibitory G proteins has direct consequences on end-organ cardiac responses to vagal activity. This study quantifies the physiological consequences of pertussis toxin-induced impairment of inhibitory G proteins in conscious animals. PMID- 8368375 TI - Free cytosolic Ca2+ measured with Ca(2+)-selective electrodes and fura 2 in rat mesenteric resistance arteries. AB - Free cytosolic Ca2+ was measured with sub-micrometer-tip, double-barrelled, Ca(2+)-selective electrodes and fura 2 in rat mesenteric resistance arteries. The purpose was to establish intracellular free Ca2+ concentration ([Ca2+]i) values in resting and stimulated vessels. Isolated vessels were mounted for isometric force measurements. Measured with electrodes, mean [Ca2+]i was 115 and 708 nM under resting and norepinephrine-activated conditions, respectively. Fura 2 was calibrated intracellularly including determination of the intracellular dissociation constant (Kd) of the fura 2:Ca2+ complex. The intracellular Kd was 342 nM. With this value of Kd, fura 2 measurements of mean [Ca2+]i were 129 and 537 nM under resting and norepinephrine-activated conditions, respectively. The values measured with the two techniques were thus in good accordance. PMID- 8368376 TI - Adult rat ventricular myocytes cultured in defined medium: phenotype and electromechanical function. AB - We studied primary short-term cultures of adult rat ventricular myocytes in defined medium to determine whether phenotype and electromechanical function are maintained in rod-shaped, quiescent cells. Although > 80% of the myocytes retained their rod-shaped in vivo morphology for up to 72 h, contractile function as measured by cell edge motion declined 30-50% from 6 to 24 h, paralleling a 68% shortening of action potential duration. From 24 to 72 h, contractility remained unchanged. Ca2+ channel current density increased 55% after 24-48 h and then returned to the level of freshly isolated cells (9 +/- 1 pA/pF, mean +/- SE). Resting membrane potential (-71 +/- 1 mV) and action potential overshoot (34 +/- 3 mV) did not change. The ratio of alpha- to beta-myosin heavy chain mRNA and the level of cardiac alpha-actin mRNA were maintained for 8 days. Thus quiescent adult rat ventricular myocytes in defined medium undergo extensive phenotypic adaptation within 72 h of isolation, despite maintenance of a rod-shaped morphology and stable levels of contractile protein mRNA, which may limit their suitability for electrophysiological and contractile function studies. PMID- 8368377 TI - A method for isolating rabbit atrioventricular node myocytes which retain normal morphology and function. AB - This report describes a method for isolating single rabbit atrioventricular (AV) node myocytes which retain their normal morphology when exposed to millimolar levels of calcium. Previous attempts to isolate cells from the AV node have produced myocytes that "round up" (i.e., go into contracture) when exposed to calcium. We show that the cells isolated with our technique possess properties similar to those described for intact AV nodal tissue. We find that single AV node myocytes are shorter and thinner (mean dimension = 103.5 +/- 2.3 by 7.8 +/- 0.2 microns; mean +/- SE, n = 90) than atrial or ventricular cells. Many of the cells produced by this isolation procedure generate spontaneous action potentials (188 +/- 9 beats/min; n = 6), which resemble action potentials recorded previously from the intact AV node. Voltage-clamp recordings from spontaneously active cells revealed similar membrane currents to those seen in intact tissue: fast sodium current and a L-type calcium current, followed by a delayed outward current. However, we found little evidence for the hyperpolarization-activated current (I(f)). Because the cells responded normally to concentrations of acetylcholine and isoproterenol within the physiological range, their cholinergic and adrenergic receptors appear to be well preserved by the isolation procedure. The ability to isolate morphologically and functionally normal AV myocytes may represent a significant advance for the investigation of nodal physiology at the cellular level. PMID- 8368378 TI - Calcitonin gene-related peptide mediates hypotension and tachycardia in endotoxic rats. AB - Circulating calcitonin gene-related peptide (CGRP) concentrations are elevated in experimental and clinical sepsis. CGRP causes hypotension and tachycardia, suggesting that the peptide might mediate the acute circulatory changes in sepsis. To test this hypothesis we administered Escherichia coli endotoxin (8 mg/kg iv) to Nembutal- (pentobarbital sodium; 50 mg/kg) anesthetized rats. Endotoxin caused hypotension and tachycardia within 60 min that stabilized for 90 min. After 2 h more severe hypotension developed, and 80% of rats died spontaneously after 3 h. In other endotoxic rats we administered 20 nmol of the CGRP receptor antagonist hCGRP (8-37) intravenously at 60 min. hCGRP (8-37) transiently reversed tachycardia (from 469 +/- 11 to 407 +/- 7 beats/min, P < 0.05) and increased mean blood pressure (from 63 +/- 4 to 93 +/- 11 mmHg, P < 0.05) over 30 min, after which hemodynamics and survival rates were no different from untreated animals. The results suggest that CGRP plays an important role in the acute circulatory changes of endotoxemia. More detailed work is necessary to determine the effects of CGRP antagonism on cardiac function, regional blood flow, and overall survival rates in sepsis. PMID- 8368379 TI - Excitatory amino acid receptors within NTS mediate arterial chemoreceptor reflexes in rats. AB - The nucleus tractus solitarius (NTS) is the primary site of termination of arterial baroreceptor and chemoreceptor afferent fibers. Excitatory amino acid (EAA) receptors within NTS have been shown to play an important role in the mediation of arterial baroreceptor reflexes; however, the importance of EAA receptors within NTS in the mediation of arterial chemoreceptor reflexes remains controversial. Therefore, in chloralose-urethan-anesthetized, mechanically ventilated, paralyzed rats, 4 nmol of the broad-spectrum EAA receptor antagonist kynurenic acid (Kyn) was injected into the NTS to observe the effects of EAA receptor blockade on the pressor responses evoked by either activation of ipsilateral carotid body chemoreceptors (by close arterial injection of CO2 saturated bicarbonate) or electrical stimulation of ipsilateral carotid sinus nerve (CSN). Under control conditions, activation of carotid body chemoreceptors and CSN stimulation evoked increases in arterial pressure of 27 +/- 2 (n = 24 sites) and 28 +/- 3% (n = 8), respectively. Kyn microinjection into NTS significantly reduced the pressor responses evoked by activation of carotid body chemoreceptors and electrical stimulation of the CSN for 20 and 25 min, respectively. Attenuation of pressor responses evoked by chemoreceptor activation were maximal at 20 min post-Kyn injection (13 +/- 2%), whereas CSN-evoked pressor responses were maximally attenuated at 15 min (6 +/- 4%). Microinjection into NTS of 4 nmol of xanthurenic acid, a structural analogue of Kyn with no EAA receptor antagonist properties, had no effect on chemoreceptor reflexes. We conclude that EAA receptors within NTS play an important role in the mediation of arterial chemoreceptor reflexes. PMID- 8368380 TI - Stress and cocaine elicit similar cardiac output responses in individual rats. AB - Cocaine use and behavioral stress elicit variable cardiovascular responses in individuals. In the present study, we examined the effects of cocaine or stress on arterial pressure, heart rate, and cardiac output in conscious rats. Rats were instrumented for determination of ascending aortic blood flow as an index of cardiac output using pulsed Doppler flow-metry. Cocaine administration elicited consistent decreases in cardiac output in some rats, whereas others had increases. In contrast, the pressor and heart rate responses were similar in these two groups of animals. Air jet stress also elicited a decrease in cardiac output only in a subset of conscious rats, yet produced equivalent pressor responses in all rats. Cardiac output responses to cocaine and air jet stress were closely correlated in individual rats, indicating that these stimuli evoke similar hemodynamic responses in individual rats. These observations suggest that the rat may provide a model for understanding differential cardiovascular sensitivity to cocaine and/or stress in humans. PMID- 8368382 TI - Carrier-mediated transport of lactic acid in cultured neurons and astrocytes. AB - The glycolytic end product lactic acid induced a rapid transient decrease in cytosolic pH in cultured neurons and astrocytes, as measured by microspectrofluorometry using the fluorescent indicator dye 2',7'-bis-(2 carboxyethyl)-5-(and-6) carboxyfluorescein acetoxymethyl ester. Over a physiological range of pH, the initial rate of cellular acidification was a saturable function of the extracellular lactate concentration, suggesting that a saturable transport system mediated lactic acid permeation across the plasma membrane. This transport process displayed stereoselectivity, with a threefold higher rate of intracellular acidification by L-lactic acid than by its D-isomer. Lactic acid-induced acidification occurred in the absence of intracellular ATP, suggesting that transport proceeded independently of the cellular energy charge. These data suggest the existence of a lactic acid carrier in mammalian neuronal and astrocytic plasma membranes, which might serve an acid-scavenging function under conditions of altered pH homeostasis. In the setting of in vivo cerebral ischemia, this carrier may promote the efflux of lactic acid from astrocytes, redistributing it among less metabolically active neurons. PMID- 8368381 TI - Laryngeal afferent inputs to the nucleus of the solitary tract. AB - The following study was undertaken to examine the integration of laryngeal afferent inputs within the nucleus of the solitary tract (NTS), the primary site of termination of laryngeal afferent fibers. Intracellular recordings were obtained from 63 cells that responded to electrical stimulation of the superior laryngeal nerve (SLN) with an excitatory postsynaptic potential (EPSP; n = 49), an excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequence (n = 13), or an IPSP (n = 1). Mechanical stimulation of laryngeal mechanoreceptors revealed a variety of response patterns (e.g., slowly and rapidly adapting depolarizations or hyperpolarizations). Two types of response to increasing SLN stimulus frequency were observed. In 11 cells SLN-evoked EPSP amplitude at 10 Hz was only 47 +/- 4% of the amplitude at 1 Hz, while in 6 cells EPSP amplitude at 10 Hz was virtually identical (93 +/- 3%) to that at 1 Hz. Time-dependent inhibitory interactions occurred between SLN inputs to NTS neurons at intervals between 50 and 400 ms and in the absence of any change in membrane potential. NTS neuronal responses to brief activation of laryngeal mechanoreceptors correspond well to discharge patterns described for individual laryngeal mechanoreceptors. Frequency dependent filtering and time-dependent inhibitory interactions might modify NTS neuronal responses during more intense stimulation of laryngeal afferents. PMID- 8368383 TI - Effects of renal receptor stimulation on neurons within the ventrolateral medulla of the cat. AB - Experiments were performed to determine if activation of renal receptors by occlusion of the renal artery, renal vein, or ureter would alter activity of cells within the ventrolateral medulla of the cat. Extracellular unit recordings were obtained from 195 cells located within the rostral ventrolateral medulla of 90 alpha-chloralose-anesthetized cats. Fifty-five of 195 cells (28.2%) tested for responses to renal receptor activation responded to at least one of the occlusions. Occlusion of the ureter increased the activity of 25 cells from 9.7 +/- 3.7 to 23.0 +/- 6.5 impulses/s and decreased the activity of 5 cells from 11.9 +/- 3.6 to 3.5 +/- 1.2 impulses/s. Occlusion of the renal vein increased the activity of seven cells from 7.5 +/- 3.3 to 22.3 +/- 7.3 impulses/s and decreased the activity of six cells from 13.8 +/- 3.8 to 4.1 +/- 2.0 impulses/s. Renal artery occlusion elicited solely excitatory responses from 43 cells. Thirty-one of the 43 cells increased their activity within 0-3 s of the onset of renal artery occlusion from 4.1 +/- 0.8 to 12.6 +/- 1.2 impulses/s. Renal artery occlusion increased the activity of 10 out of 43 cells with a mean latency of 26.1 +/- 6.5 s from 8.3 +/- 2.5 to 29.6 +/- 9.3 impulses/s. Twenty-four of the 55 (43.6%) responders were responsive to two or more forms of renal receptor activation. These results demonstrate that activation of renal mechanoreceptors and chemoreceptors affects cells within the ventrolateral medulla of the cat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368384 TI - Influence of extent of muscle shortening and heart rate on work from frog heart trabeculae. AB - Shortening, lengthening, and net work done by frog (Rana pipiens) heart trabeculae were measured over a range of strain amplitudes (length change) and cycle frequencies. Net work, the product of muscle strain and force over a full lengthening/shortening cycle, increased with strain to strains well over 25% of the muscle's rest length, a value greater than optimum strains reported for most skeletal muscles. A distinct optimum strain for net work was not found. Maximum net work per cycle averaged 7.5 J/kg for ventricular muscle and 2.0 J/kg for atrial muscle. Isometric twitch stress was maximal at 0.4-0.6 Hz twitch frequency in ventricular trabeculae (average 51 kN/m2) and 0.6-1.4 Hz in the atrium (average 14 kN/m2). The twitch duration decreased with increasing twitch frequency. Shortening and net work were maximal at 0.7-Hz cycle frequency in ventricular trabeculae and 0.9 to 1.4 Hz in the atrium. The decline in work per cycle at slower frequencies was due in part to a decline in twitch force. Maximum power for the ventricle was approximately 5 W/kg and occurred at 0.8 Hz and 26% strain, and was 1/3 to 1/4 the power of most skeletal muscles studied at similar temperatures. PMID- 8368385 TI - Intragastric glucose but not fructose conditions robust flavor preferences in rats. AB - Prior work indicates that glucose and fructose differ in their postingestive reinforcing effects. The present study investigated this phenomenon by training rats to associate the intake of flavored water with intragastric (IG) infusions of 16% sugar solutions. In experiment 1, rats had one flavor [conditional stimulus (CS)] paired with IG sugar infusions (CS+; e.g., cherry) and another flavor paired with IG water (CS-; e.g., grape) 23 h/day; Chow was available ad libitum. In subsequent choice tests, rats infused with glucose displayed a strong preference (89%) for the CS+ flavor, whereas rats infused with fructose showed only a small and nonreliable CS+ flavor preference (62%). When next trained to associate one flavor (e.g., orange) with IG glucose and another flavor (e.g., strawberry) with IG fructose, rats in both groups developed a significant preference (81%) for the glucose-paired flavor. In experiment 2, food-deprived rats were trained 2 h/day to associate a CS+ flavor with IG sugar and a CS- flavor with IG water infusions. The glucose-reinforced rats displayed a near total preference (95%) for the CS+ flavor, whereas fructose-reinforced rats showed a much smaller CS+ preference (67%). The preference findings indicate that the postingestive consequences of glucose are much more reinforcing than those of fructose. It appears that food conditioning is mediated by chemospecific actions of nutrients rather than their general satiating or energy repleting effects. PMID- 8368387 TI - Enhanced response of muscle protein synthesis and plasma insulin to food intake in suckled rats. AB - To compare the sensitivity of muscle protein synthesis to food intake in neonatal and weaned rats, 5- and 16-day-old suckled rats and 28-day-old weaned rats were either fed, fasted for 8-10 h, or refed for 1-4 h after an 8-h fast. Protein synthesis was measured in vivo in soleus and plantaris muscles with a large dose of L-[4-3H]phenylalanine. In fed rats, fractional rates of protein synthesis (KS) decreased with age. Fasting decreased KS, and refeeding increased KS most in 5 day-old animals, less in 16-day-old rats, and least in 28-day-old rats. In 5-day old rats, there were no differences in KS between soleus and plantaris muscles in the fed state and after fasting and refeeding; at 28 days, KS was higher in soleus than in plantaris in fed rats, and the soleus did not respond to fasting and refeeding. In rats at all three ages, the concentration of most plasma amino acids decreased during fasting; when 5-day-old rats were refed, plasma amino acid concentrations increased, but not to the levels in the fed state. Plasma insulin concentrations increased with age. Plasma insulin concentrations decreased more rapidly with fasting and increased more extensively with refeeding in 5-day-old rats than in older rats. These results suggest that muscle protein synthesis is more responsive to food intake in young suckled rats than in older suckled or weaned rats; this increased responsiveness is accompanied by greater changes in circulating insulin concentrations. PMID- 8368386 TI - Induction of c-fos expression in spinal neurons by nociceptive and nonnociceptive stimulation of LUT. AB - Expression of c-fos gene in spinal neurons was detected with an immunocytochemical technique to study the spinal processing of nociceptive and nonnociceptive input from the lower urinary tract (LUT) of the urethan anesthetized rat. Two preparations were used to activate afferent pathways in the LUT: 1) the urinary bladder was exposed through an abdominal incision, and saline or 1% acetic acid solution was infused directly into the bladder lumen and expelled through the urethra; and 2) the bladder was catheterized through the urethra, and the urethral outlet was ligated to allow distension and reflex contractions to occur under isovolumetric conditions. The first preparation mimicked the physiological changes occurring during normal voiding, whereas the second preparation generated high (presumably nociceptive) pressures when the bladder contracted against a closed outlet. The results indicate that distension induced voiding increased c-fos expression largely in the region of the sacral parasympathetic nucleus (52% of the total number of cells/L6 section) and the dorsal commissure (25% of the total number of cells), whereas nociceptive stimuli markedly increased the number of c-fos-positive cells in the dorsal commissure (3.5 x increase above the number induced by distension, representing 50% of the total number of cells/L6 section). Bladder contractions against a closed outlet elicited a distribution of c-fos-positive cells similar to that induced by chemical irritation. Drugs that suppressed bladder reflexes did not reduce c-fos induced by distension, indicating that voiding reflexes do not contribute to c fos expression. PMID- 8368388 TI - Mechanisms of potassium transfer across the dually perfused rat placenta. AB - The purpose of this study was to directly investigate the mechanisms of K+ transfer across the rat placenta, which was isolated and perfused through both its maternal and fetal circulations. Unidirectional maternofetal (Kmf) and fetomaternal (Kfm) clearances for 42K, 51Cr-labeled EDTA (used as a diffusion limited paracellular marker), and 3H2O (used as a flow-limited marker) were respectively 232 +/- 36, 12 +/- 4, and 1,020 +/- 260 (mf) and 96 +/- 26, 18 +/- 6, and 737 +/- 176 (fm) microliters.min-1 x g placenta-1. Calculated K+ fluxes were asymmetric, being 0.75 +/- 0.12 and 0.41 +/- 0.12 mumol.min-1 x g placenta-1 for maternofetal and fetomaternal, respectively (mean +/- SE, n = 6; P < 0.01, paired t test). Although Kmf for 3H2O was 28% higher than Kfm, this could not completely account for the asymmetry in K+ fluxes. Kmf for 42K was 12-70 times higher than that for 51Cr-EDTA (presumed to be a paracellular marker), although its diffusion coefficient is only 2.5 times higher. An apparent Michaelis constant (Km) of 11.0 +/- 2.4 mM and maximum velocity (Vmax) of 3.8 +/- 0.33 mumol.min-1 x g placenta-1 was calculated by Michaelis-Menten analysis of the transcellular component of maternofetal flux (Jmf) for K+. Ouabain or barium (1 mM in maternal and fetal perfusate) reduced Kmf for 42K from 250 +/- 38 to 76 +/- 13 microliters.min-1 x g placenta-1 (n = 4; P < 0.01) and from 358 +/- 31 to 106 +/- 18 microliters.min-1 x g placenta-1 (n = 5; P < 0.001). Neither drug had any effect on Kmf for 51Cr-EDTA or 3H2O.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368389 TI - Impairment of insulin action on peripheral glucose uptake and hepatic glucose production in tumor-bearing rats. AB - The present study was performed to determine the time-course for the development of peripheral and hepatic insulin resistance in rats as a result of an increasing tumor burden. Animals were inoculated with Yoshida ascites hepatoma, and studies were conducted during the early phase of tumor growth (day 4) at which time there was no change in food intake and at a later time point (day 8) when the tumor burden was increased and rats demonstrated anorexia. In vivo insulin action was accessed under euglycemic hyperinsulinemic conditions, in which insulin was infused at rates sufficient to produce arterial insulin levels that represent high physiological (3.5 ng/ml) or maximally stimulating values (180 ng/ml). On day 4, tumor-bearing (TB) rats were euglycemic, and whole body glucose turnover was elevated 32%. Insulin-mediated glucose uptake (IMGU) in TB rats was similar to control values at the low insulin infusion rate but reduced by 53% under maximally stimulating conditions. The insulin-induced suppression of glucose production was similar in TB and control animals at this time point. In contrast, on day 8, TB rats were hypoglycemic and glucose turnover was reduced 35%. The impairment in IMGU was more severe than seen earlier, with glucose uptake being reduced 39 and 61% at both levels of hyperinsulinemia. At this time point, the ability of insulin to inhibit glucose production was also impaired. These results indicate that the insulin resistance induced by the Yoshida hepatoma was manifested initially by a reduction in IMGU by peripheral tissues. As the tumor burden increased peripheral insulin resistance became more severe and an impairment in hepatic insulin action was observed. PMID- 8368390 TI - Effect of exercise training on RSNA, baroreflex control, and blood pressure responsiveness. AB - The effect of exercise training (ET) on renal sympathetic nerve activity (RSNA), baroreflex control of RSNA and heart rate (HR), and arterial pressure (AP) responsiveness to phenylephrine and angiotensin II (ANG II) was studied in six trained (T) and six sedentary (S) male Wistar rats. ET was performed on a motor treadmill for 13 wk. The RSNA signals of unanesthetized rats were processed by an analog-to-digital converter to quantify the nerve discharges associated with changes in AP and HR. The reflex control of RSNA and HR were evaluated during progressive injections of phenylephrine and sodium nitroprusside. Mean arterial pressure (MAP) was similar in both groups. RSNA was significantly lower in T rats (28 +/- 2 vs. 36 +/- 3%). T rats had an impairment of baroreflex control of RSNA in response to nitroprusside (4.9 +/- 0.89 vs. 12.3 +/- 1.2 bars.cycle-1.mmHg-1). ET decreased AP responsiveness for phenylephrine and ANG II. Therefore ET produces 1) no change in resting MAP but a significant decrease in RSNA and AP responsiveness and 2) partial impairment of baroreflexes, i.e., bradycardic responses and RSNA during MAP decrease. PMID- 8368391 TI - Endogenous cholecystokinin in the control of gastric emptying of liquid nutrient loads in rhesus monkeys. AB - A role for the brain/gut peptide cholecystokinin (CCK) in the control of gastric emptying has been proposed. In the present studies, we have used a potent type A CCK-receptor antagonist (devazepide) to examine the quantitative contribution of endogenously released CCK in the control of liquid gastric emptying of 100 ml lipid, protein, and carbohydrate test loads in rhesus monkeys. Emptying was studied in conscious monkeys equipped with chronic indwelling gastric cannulas. Prior intragastric administration of devazepide (1.0-320 micrograms/kg) differentially affected the 10-min emptying of glucose (0.125/ml), peptone (4.5%), and Intralipid (4.5%). Glucose emptying was not affected by any dose of the CCK antagonist. The emptying of peptone was accelerated by doses of 10 micrograms/kg or higher. This effect, however, was only partial and plateaued at a dose of 100 micrograms/kg. The gastric emptying of Intralipid was accelerated at a dose of 32 micrograms/kg, and the inhibitory effect of the Intralipid was completely eliminated at a dose of 320 micrograms/kg. At this dose of devazepide, the Intralipid test meal emptied from the stomach at the same rate as physiological saline. These data demonstrate that in rhesus monkeys endogenously released CCK 1) does not play a role in the control of glucose emptying, 2) is a partial mediator of the inhibitory action of peptone on gastric emptying, and 3) is the primary inhibitory mediator in the control of the gastric emptying of Intralipid. PMID- 8368392 TI - Experimental cachexia: effects of MCA sarcoma in the Fischer rat. AB - Temporal patterns of the cachectic effects of tumor growth and their relation to systemic levels of tumor necrosis factor (TNF) and IL-6 (interleukin-6) were examined in a rat model of experimental cancer cachexia employing the methylcholanthrene (MCA) sarcoma. Fischer 344 rats, implanted with biotelemeters for measuring temperature and activity, were implanted subdermally with tumor tissue fragments. Ad libitum-fed and pair-fed controls were sham incised. Bioassays for TNF and IL-6 were performed on serial plasma samples, obtained via jugular vein at 3- to 6-day intervals throughout the experimental period. Tumor growth induced significant anorexia, weight loss, and a decline in motor activity corresponding to an increase in mean plasma IL-6 levels, independent of reduced food intake or weight loss alone as shown in pair-fed controls. A significant lowering of body temperature then developed, followed by a two- to threefold increase in water consumption. The patterns of weight loss and temperature reduction differed in rate and degree from those seen with pair feeding. PMID- 8368393 TI - Role of intrarenal ANG II in reflex neural stimulation of plasma renin activity and renal sodium reabsorption. AB - Renal sympathetic stimulation of plasma renin activity (PRA) and sodium reabsorption was examined in conscious dogs before and during intrarenal angiotensin II (ANG II)-type 1 receptor blockade with losartan (Dup-753) and converting enzyme inhibition. In uninephrectomized dogs, renal function and PRA responses to 14% blood volume depletion (BVD) were measured. BVD was utilized to activate renal sympathetic outflow in the absence of hypotension. In eight vehicle-treated dogs, 14% BVD increased PRA from 1.38 +/- 0.32 to 2.79 +/- 0.66 ng ANG I.ml-1 x h-1 and decreased urinary sodium excretion (UNaV) from 85.1 +/- 11.3 to 45.4 +/- 7.5 mueq/min. During losartan (n = 6) and captopril (n = 5) infusion, plasma renin responses were enhanced in response to 14% BVD (1.93 +/- 0.48 to 5.74 +/- 2.25 and 3.03 +/- 0.73 to 9.19 +/- 1.94 ng ANG I.ml-1 x h-1, respectively), whereas antinatriuretic responses were similar to vehicle-infused dogs. Thus, neurogenic antinatriuresis is not mediated by secondary generation of ANG II, since UNaV decreased similarly to control in all conditions of ANG II blockade. Tonic intrarenal and/or circulating ANG II synthesis of dogs on a normal sodium diet inhibit neurogenic stimulation of renin release, since PRA responses were enhanced after blockade of ANG II. PMID- 8368394 TI - Serum immunoreactive erythropoietin and red blood cell mass during pregnancy in conscious rats. AB - Serum erythropoietin concentration increases during human pregnancy and presumably accounts for expansion of red blood cell mass. The mechanism(s) underlying gestational changes of serum erythropoietin are unknown. Moreover, if erythropoietin synthesis increases, then the organ(s) questions about erythropoietin in pregnancy, we first set out to establish an animal model. Chronically instrumented, conscious unrestrained rats were studied. 51Cr-labeled red blood cells and radioimmunoassay were used to assess red blood cell mass and serum erythropoietin, respectively. Except for a lower hematocrit (P < 0.05 vs. virgin rats) and a slightly higher plasma volume (P value not significant) for gravid rats on gestational day 6, all other variables measured in early pregnancy rats were comparable to those measured in virgin control animals. Significant increases in total blood volume, plasma volume, and red blood cell mass were observed by gestational day 13 (midpregnancy) when compared with virgin control rats. These changes were even more pronounced on gestational day 20. Serum immunoreactive erythropoietin was also significantly increased at both of these stages of pregnancy. We conclude that the gravid rat is a reliable animal model of human gestation in which to further investigate erythropoietin in pregnancy. PMID- 8368395 TI - Role of decreased plasma volume in hematocrit alterations during incremental treadmill exercise in horses. AB - Six intact (IN) and six splenectomized (SP) mares were subjected to an incremental exercise test to examine the role of decreases in plasma volume (PV) in the changes in hematocrit (Hct) normally seen with exercise. Each horse underwent an incremental exercise test in which it ran on a treadmill up a fixed incline of 6 degrees. The test started at a speed of 4 m/s, and speed was increased 1 m/s each min until heart rate reached a plateau. Blood samples were obtained at rest and at the end of the 4, 5, 6, and 7 m/s steps of the exercise test. Resting PV was greater (P < 0.05) in the IN group (28.6 +/- 0.5 liters) compared with SP horses (22.7 +/- 2.2 liters). Exercise produced a significant increase in Hct in both groups of horses; however, the increases were greater (P < 0.05) at all exercise intensities in IN compared with SP horses. Hct increased rapidly during the first step (4 m/s) in the exercise test in the IN animals. After this, Hct increased slowly in IN horses, and values for the 5, 6, and 7 m/s steps paralleled the changes observed in the SP horses. Corrected Hct values were then used to calculate the relative change in PV. Exercise produced a significant decrease in PV in both groups of horses; however, there were no differences (P > 0.05) between the groups when IN horses (-13 +/- 3 and -18 +/- 2%) were compared with SP horses (-14 +/- 4 and -17 +/- 4%) at the 6 and 7 m/s steps of the exercise test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368396 TI - Splenectomy alters blood pressure response to incremental treadmill exercise in horses. AB - Six intact (IN) and five splenectomized (SP) mares were subjected to an incremental exercise test to examine the effects of splenectomy on blood pressure responses during exercise. During the test the horses ran up a 6 degree grade on a treadmill set at an initial speed of 4 m/s. Speed was increased 1 m/s every 1 min until heart rate (HR) reached a plateau. Hemodynamic data were collected continuously and analyzed for the last 18 s of the 4, 5, 6, and 7 m/s steps of the exercise test. There were no differences (P > 0.05) between the groups for resting means for any parameter measured in the study. HR increased (P < 0.05) in both groups of horses during exercise with significantly greater HR in the SP horses during the first two steps of the test. There were no differences (P > 0.05) in maximal HR between the groups. Right atrial pressure (RAP) did not change during exercise in the SP horses; however, it did increase 20 mmHg (493%, P < 0.05) in the IN horses. Right ventricular pressure (RVP) increased (P < 0.05) during exercise with no differences (P > 0.05) between the groups. Right ventricular maximum change in pressure over time increased (P < 0.05) in a similar fashion in both groups of animals. Mean arterial pressure (MAP) increased 29 mmHg (30%, P < 0.05) in SP horses, reaching a plateau by the 5 m/s step of the test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368398 TI - Rapid alterations of hypothalamic and hippocampal bombesin-like peptide levels with feeding status. AB - It has been suggested that bombesin (BN)-like peptides may play a physiological role in the control of food intake. We studied the time course of changes in the levels of central BN-like peptides during a meal. Four groups of animals were used: rats that were food (but not water) deprived for 12-h period (preprandial group) and then given access to food for either 10 min (partially satiated group) or 35 min (postprandial group). The fourth group constituted nondeprived controls (ad libitum fed group). BN-like immunoreactivity (BLI) of the hypothalamus, hippocampus, and medulla was determined using a radioimmunoassay. Our data revealed that at the hypothalamus, the BLI content dropped significantly after food deprivation (preprandially), and returned to the ad libitum fed control levels after the meal (postprandially). At the hippocampus, food deprivation did not affect the BLI levels; however, food ingestion significantly elevated the BLI content within 35 min. The medullary BLI levels failed to alter in relation to the feeding status. The observed rapid alterations suggest that the hypothalamic response to food intake is satiety linked and hence lend support to the contention that BN-like peptides play a physiological role in the central regulation of ingestive behavior. The alterations noted at the hippocampus implicate physiological role of BN-like peptides in other meal-associated processes (such as memory). PMID- 8368397 TI - Selective retention of essential fatty acids: the role of hepatic monoacylglycerol acyltransferase. AB - In the suckling rat, chick embryo, and hibernating marmot, fatty acids provide the major source of energy, and despite the high rate of hepatic beta-oxidation, these animals selectively retain long-chain polyunsaturated derivatives of C18:2n 6 and C18:3n-3. To determine whether the hepatic microsomal activity monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) could provide a mechanism to selectively acylate monoacylglycerols that contain essential fatty acids, we tested the ability of MGAT activity from each of the three species to acylate sn 2-monoC18:1-, sn-2-monoC18:2-, sn-2-monoC18:3-, and sn-2-monoC20:4-glycerols. Hepatic MGAT activity acylated sn-2-monoC18:3-glycerol and sn-2-monoC18:2 glycerol in preference to sn-2-monoC18:1-glycerol in each of the three different lipolytic animals. MGAT's acyl group specificity could not be explained by invoking differences in membrane fluidity because the apparent affinity for sn-2 monoC20:4-glycerol was not increased. Further, sn-2-monoC18:3-glycerol remained a preferred substrate under assay conditions when both the C18:3 and C18:1 species were present in equal amounts. As would be predicted in the presence of high activity of a selective MGAT, the hepatic glycerolipids from neonatal rats showed increases in dienoic, trienoic, and C22:6 fatty acids and relative decreases in monoenoic, saturated, and C20:4 fatty acids. We hypothesize that, during lipolysis, the reacylation of sn-2-monoacylglycerols by MGAT may provide a mechanism by which essential fatty acids are retained within specific tissues. PMID- 8368399 TI - Vascular effects of arginine vasotocin in toad skin. AB - Fluid balance in amphibians is regulated, in large part, by arginine vasotocin (AVT). One important action of this hormone is to facilitate water uptake by increasing the water permeability of the skin. Cutaneous blood flow also affects water uptake, but the effects of AVT on skin perfusion are unknown. This study tested the hypothesis that AVT facilitates water uptake, not only by increasing cutaneous water permeability, but also by promoting cutaneous blood flow. The effects of AVT on blood flow through the ventral pelvic skin, a region specialized for water uptake, were assessed in Bufo marinus by determining the conductance of the skin to acetylene (GsAc), an index of cutaneous blood flow. A pump-perfused skin preparation was used to study the effects of AVT on the cutaneous vascular resistance (CVR) of the ventral pelvic skin and the dorsal skin (a region not normally involved in water uptake). Bolus AVT injections (iv) of 10 pmol/kg and below had no significant effect on GsAc (P > 0.45). However, 100 and 300 pmol/kg of AVT decreased GsAc by 39 +/- 7 (P < 0.001) and 63 +/- 6% (P < 0.001), respectively. The higher AVT doses increased mean arterial pressure. AVT increased CVR in both pump-perfused preparations. The lowest concentration of AVT tested that significantly raised CVR was 1 x 10(-10) M for the dorsal skin (P = 0.006) and 3 x 10(-10) M for the ventral pelvic skin (P = 0.038).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368400 TI - Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle. AB - Insulin or exercise stimulates skeletal muscle glucose transport, most likely by increasing both the number and activity of glucose transporters in the plasma membrane. Skeletal muscle glucose transport of genetically obese Zucker rats (fa/fa) displays a severe insulin resistance that results, at least in part, from a failure of net transporter translocation to the cell membrane (King, P., E. D. Horton, M. Hirshman, and E. S. Horton. J. Clin, Invest. 90: 1568-1575, 1992). The purpose of the present study was to determine if the obese rat muscle was also resistant to the action of acute exercise to increase glucose transport and, if so, to determine if the defect involved transporter translocation as seen in the resistance to insulin. The muscle glucose transport system was investigated in plasma membranes isolated from postprandial, sedentary or acutely exercised, lean and obese Zucker rats. Measurements of D- and L-glucose uptake by membrane vesicles under equilibrium exchange conditions indicated that an acute bout of exercise resulted in a threefold increase in the maximum velocity (Vmax) for lean animals (5.7 vs. 17.6 nmol.mg protein-1.min-1) and a 4.5-fold increase in the Vmax for obese rats (4.1 vs. 18.6 nmol.mg protein-1.min-1). For both lean and obese animals, this increase in transport was associated with an increase in transporter number measured by cytochalasin B binding (1.6- and 2.2-fold, respectively) and with an increase in the average carrier turnover number (1.9- and 2.0-fold, respectively). The results indicate that, unlike a maximal insulin stimulus, acute exercise of the obese Zucker rat promotes both transporter translocation and transporter activation in skeletal muscle. PMID- 8368401 TI - Central interferon-alpha inhibits natural killer cytotoxicity through sympathetic innervation. AB - The brain has been known to produce high levels of interferon-alpha (IFN-alpha) during viral infections. We investigated the central and peripheral mechanisms of the brain IFN-alpha-induced suppression of natural killer (NK) cytotoxicity in the rat. The activity of NK cells in the spleen and the peripheral blood decreased 30-120 min after intracerebroventricular (icv) injection of recombinant human IFN-alpha of > 1,000 U but not after its intraperitoneal injection. This effect was antagonized by pretreatment with icv naltrexone (NLTX). Splenic denervation was observed to completely abolish the IFN-alpha-induced suppression of NK activity, whereas bilateral adrenalectomy did not. Furthermore, this immunosuppression was blocked by an icv injection of an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF-(9-41). The icv injection of CRF resulted in reduced NK activity, which was not affected by NLTX. The results suggest that brain IFN-alpha activates the CRF system through central opioid receptors and thereby suppresses the NK cytotoxicity predominantly through splenic sympathetic innervation. PMID- 8368402 TI - Vasopressin-independent alterations in renal water excretion in quadriplegia. AB - Postural effects on water excretion are known to be increased in patients with cervical spinal cord injury and may result in marked impairment of the ability to excrete a water load, especially in erect posture. Both vasopressin-dependent and vasopressin-independent mechanisms have been implicated. To assess the roles of these mechanisms and further identify the factors involved in the renal response to erect posture, sustained water loading studies were performed on 11 quadriplegic subjects and 9 healthy control subjects, supine and erect (sitting). Renal blood flow was assessed by p-aminohippurate clearance (CPAH) measurements in 7 quadriplegic and 5 control subjects. During maximal water diuresis, plasma vasopressin concentrations were reduced to unquantifiable levels in all subjects. Osmolar clearance, free water clearance (CH2O), and distal delivery of filtrate (DDF) were all lower in quadriplegic than in control subjects, supine and erect. The relationship between CH2O and DDF was the same in quadriplegic as in control subjects and was not altered by change in posture in either group. Creatinine clearance and CPAH were lower in erect than in supine posture in quadriplegic subjects but not in control subjects. We conclude that impairment of water excretion in stable normonatremic quadriplegic subjects can be attributed primarily to vasopressin-independent mechanisms involving reduced filtrate delivery to diluting segments of the renal tubules rather than to resistance to normal suppression of vasopressin release. PMID- 8368403 TI - Effects of long-term restricted feeding on motor activity rhythm in the rat. AB - The motor activity circadian rhythm of the rat is driven by at least two different pacemakers, one entrained by light-dark cycles and the other by periodic food access. The interaction between these two pacemakers generates the overt rhythm in many variables in the rat. In this paper we study the effects of restricted feeding (RF) for > 300 days on the motor activity of two groups of eight rats each (4 males and 4 females) that were kept under different light patterns. The first group was kept under dim red light, and the second group was kept initially for 70 days under bright light and afterward under dim red light. Rats had access to food for only 2 h/day. Results show that strong alterations in the motor activity pattern, such as relative coordination, bouncing, and several cases of entrainment, are shown in the first group. When these animals return to ad libitum feeding conditions the presence of the food component is clear, in some cases for > 20 days. In contrast, the rats that were previously subjected to bright light did not entrain to RF. In this group, there was a masking effect when lights were on, but a free-running component appeared when lights were off. The endogenous period (tau) of this component was not modified during the course of the experiment. After RF these rats showed a longer tau than the former group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368404 TI - High-density localization of ANP receptors in chondrocytes of eel gill cartilage. AB - Very high levels of atrial natriuretic peptide (ANP) receptor were found in a quite unexpected tissue, i.e., the chondrocyte of the eel gill cartilage. 125I labeled ANP binding assay indicated that the eel gill contains large amounts of the receptor and its levels are much higher (> 10-fold) than those in the other tissues examined, including the brain, kidney, head kidney including steroidogenic interrenal cells, and gut. Autoradiography using gill sections revealed dense localization of ANP receptors in the chondrocytes of the cartilage as well as moderate localization in the parenchymal cells. Biochemical and pharmacological characterization of the chondrocyte receptor indicated that most of the receptors are type C receptors, having a broad ligand specificity and a reduced M(r) of 68,000. Because a hyaline cartilage in which chondrocytes reside lacks blood vessels, and all metabolic exchange is by slow diffusion through the matrix, the chondrocyte localization of the type C ANP receptor is notable and may stimulate not only chondrocyte research but also studies on physiological significance of the type C receptor, which is generally considered to be merely a clearance (silent) receptor. PMID- 8368405 TI - Storm warnings. PMID- 8368406 TI - Isolated posterior cruciate ligament reconstruction. Long-term results. AB - From 1973 to 1987, 28 patients seen at our institution sustained isolated posterior cruciate ligament tears. Of these 28 patients, 25 were reevaluated at an average followup of 7 years and 1 month after secondary reconstruction of the posterior cruciate ligament using the semitendinosus and gracilis tendons alone or with an extraarticular procedure. Subjectively, 22 of 25 patients related no restrictions regarding activities of daily living, with 14 of 25 patients being able to return to their previous competitive level in sports. Objective evaluation after reconstruction revealed no change in the preoperative and postoperative posterior drawer examination in 13 of 25 patients, a finding confirmed by KT-1000 arthrometer measurements. Radiographic evaluation revealed degenerative changes predominantly involving the medial and patellofemoral compartments in 15 of 25 patients. Despite optimistic subjective reporting, this long-term retrospective study reveals that this procedure inconsistently limits posterior instability and therefore cannot be recommended. PMID- 8368407 TI - Tarsometatarsal joint injuries in the athlete. AB - This is a retrospective review of the presentation, diagnosis, treatment, and outcome of 19 patients who injured the tarsometatarsal joint of the foot during athletic activity. Diagnosis by clinical and radiographic examination was supplemented by stress fluoroscopy of the articulation under anesthesia. Injuries were classified as either a first- or second-degree sprain of the tarsometatarsal joint, a third-degree sprain (with diastasis between the metatarsals or cuneiforms), a fracture, or frank dislocation. Poor functional results were seen in those for whom diagnosis was delayed and for whom the injury was not treated adequately. Three patients were unable to return to sports, one of whom eventually required fusion of the tarsometatarsal joint. The third-degree sprains were indistinguishable from fracture and fracture-dislocations in that good results were not reliably obtained by nonoperative treatment, and both classes of injury seem to require open reduction and internal fixation for optimal return to function. The delay in return to full activity is a marker of the severity of this injury despite an often benign appearance on radiograph. PMID- 8368408 TI - Arthroscopy of the knee. Ten-day pain profiles and corticosteroids. AB - A prospective study was conducted to determine 10-day pain and analgesic use profiles of outpatients after arthroscopic surgery of the knee and to examine the effects of oral corticosteroid use on analgesic intake, perceived pain, and functional outcomes. Sixty-two patients who underwent a variety of arthroscopic procedures of the knee were matched on level of injury and surgical repair, and were assigned to two groups. The experimental group received a standard dosage of oral postoperative corticosteroids. The placebo group received the same dosage of a placebo (sugar pill). Both groups received the same prescription of an analgesic for pain relief after surgery. Results indicated that there were no significant differences for any dependent variables between the experimental and placebo groups. There were significant (P < 0.001) decreases in analgesic use and perceived pain throughout the 10 days. Conclusions were that most patients who have undergone arthroscopic surgery of the knee perceive pain at low levels, use limited amounts of analgesics, and return to work within a week. The addition of oral corticosteroids does not influence this profile. PMID- 8368409 TI - Postoperative pain after anterior cruciate ligament reconstruction using a transligamentous approach. AB - Anterior cruciate ligament reconstruction by free patellar tendon graft was performed using 2 different surgical approaches to the intercondylar notch in 67 consecutive patients with chronic anterior cruciate ligament insufficiency. In the first 30 patients (Group A), the traditional medial parapatellar arthrotomy with lateral luxation of the patella was done, whereas in the last 37 patients (Group B) a transpatellar tendon approach was used. Postoperative pain was managed by analgesics and, in patients who had epidural anesthesia, by administration of bupivacaine in indwelling catheters. Generally, the analgesics and bupivacaine were given immediately on request to establish comfort at rest and to permit range of motion exercises without severe pain. Compared with those in Group A, the patients of Group B had a significantly longer period from the first dose of analgesic or bupivacaine to the second, and the total number of doses of analgesic or bupivacaine was significantly lower. In the subgroup of patients with epidural anesthesia (21 in Group A and 32 in Group B), the Group B patients required significantly less analgesics, as doses equivalent to 10 mg of morphine, compared with that of Group A. PMID- 8368410 TI - An evaluation of pre- and postoperative nonsteroidal antiinflammatory drugs in patients undergoing knee arthroscopy. A prospective, randomized, double-blinded study. AB - The potential benefits of a nonsteroidal antiinflammatory drug to 67 patients undergoing knee arthroscopy were evaluated in a prospective, randomized, placebo controlled, double-blinded study. Group A received the drug (diclofenac, 75 mg twice daily) for 3 to 5 days before and for 7 days after surgery. Group B received a placebo preoperatively and the drug postoperatively. Group C received a placebo at both times. Codeine was available postoperatively for all patients if needed. Outcomes reported by the subjects included pain, crutch use, and return to activities. Outcomes assessed by physicians included knee effusion, range of motion, and gait. Knee flexion and extension strengths were measured isokinetically pre- and postoperatively. Pain scores on the 1st postoperative day were higher in Group C than in Group A. Pain scores at all other time points were not significantly different in the three treatment groups. Groups A and B required less codeine during the first 72 hours after surgery than Group C (mean, 2.9 +/- 1.0 versus 6.8 +/- 1.0 pills). Recovery of function, recovery of strength, and physical examination parameters were not significantly different in the three treatment groups. Diclofenac was an effective analgesic in the immediate postoperative period. Recovery from arthroscopy, however, was not enhanced by taking the drug. PMID- 8368411 TI - Thermal effects on skeletal muscle tensile behavior. AB - The effect of temperature on the mechanical failure properties of rabbit skeletal muscle (tibialis anterior and extensor digitorum longus) was examined. For all tests, one leg was maintained at 25 degrees C and the contralateral leg at 40 degrees C. Muscles were pulled to failure according to assignment into one of three groups: 1) passive failure at 10 cm/sec, 2) passive failure at 1 cm/sec, or 3) active (muscle is stimulated to contract as it is pulled) failure at 10 cm/sec. Load to failure was higher in the cold muscle for all groups tested. Total deformation was the same except in Group 1, when the warm muscle had a greater deformation. Energy absorbed before failure was greater in the cold muscle in Groups 2 and 3. Stiffness was higher in cold muscles for all muscles except the extensor digitorum longus in Group 1. In this study, temperature had a significant effect on the tensile properties; these thermal effects were dependent on both loading rate and contractile state. Comparing loading rates, warm muscle tested at 10 cm/sec had higher failure loads than that tested at 1 cm/sec. Comparing stimulated versus unstimulated muscle (Group 1 versus Group 3), the stimulated tibialis anterior muscle absorbed more energy than unstimulated ones. Stimulated extensor digitorum longus muscles had higher failure loads, absorbed more energy, and were stiffer than nonstimulated muscles. This study offers experimental data to support the theory that warming muscles can aid in injury prevention and improvement in athletic performance. PMID- 8368412 TI - Evaluation of arthroscopic anterior cruciate ligament reconstruction using magnetic resonance imaging. AB - Thirty-two patients who had arthroscopic anterior cruciate ligament reconstruction using a bone-patellar tendon-bone autograft underwent subsequent magnetic resonance imaging of the knee. A total of 32 magnetic resonance imaging examinations were performed from 10 days to 39 months postoperatively. The anatomic plane of the autograft was determined by obtaining a coronal pilot scan of the graft fixation screws or screw and staple. T1-weighted, T2-weighted, proton density, and gradient-echo imaging sequences were then obtained in the anatomic plane, as well as T1-weighted coronal images. The autograft was defined on the basis of visualization of fiber continuity on T2-weighted images as follows: 1) intact; 2) having a partial tear; or 3) having a complete tear. These results were then correlated with clinical examination and, in 10 cases, subsequent arthroscopy. Magnetic resonance imaging correlated with clinical findings in 31 of 32 patients. In addition, of the 10 patients who underwent subsequent arthroscopy, magnetic resonance scanning correlated in all cases with arthroscopic findings. T2-weighted and, in some cases, proton density images were most useful in visualizing the autograft. T2-weighted magnetic resonance imaging in the anatomic plane of the anterior cruciate ligament autograft can be a useful diagnostic tool in the evaluation of patients with patellar tendon anterior cruciate ligament reconstructions when graft integrity is in question. PMID- 8368413 TI - Magnetic resonance imaging of injury to the lateral ankle ligaments. AB - To establish the value of magnetic resonance imaging in determining which patients with ankle sprains will benefit from surgical treatment, 1 uninjured volunteer and 15 patients with acute, subacute, and chronic injuries of the lateral ankle ligaments were imaged at 1.0 tesla using a fast imaging with steady state precision three-dimensional technique and 1.5-mm slice thickness. A dedicated knee coil was used to hold the foot in a neutral or plantar-flexed position. In cases of acute, low-grade injuries, fraying of the anterior talofibular ligaments with intact calcaneofibular ligaments was observed in the presence of edema and hemorrhagic fluid. In cases of acute, high-grade sprains, the calcaneofibular ligament appeared wavy or was visualized only partially or not at all. Subacute injuries showed ligament disruption; chronic lesions, on occasion, showed atrophy of the calcaneofibular ligament but no edema or hemorrhagic fluid. These findings showed a good qualitative correlation with the results of graded stress radiography. Magnetic resonance imaging can definitely determine the ligaments involved in lateral ankle sprains and provide useful anatomic information in cases in which acute or reconstructive surgery is contemplated. However, the magnetic resonance imaging findings do not directly correlate with degree of instability and do not replace those of physical examination or routine radiographic studies. PMID- 8368414 TI - Intercondylar notch size and anterior cruciate ligament injuries in athletes. A prospective study. AB - Published reports agree that there is a strong association between intercondylar notch stenosis and anterior cruciate ligament injuries. In a previously published retrospective study on bilateral anterior cruciate ligament injuries and associated intercondylar notch stenosis, we formulated the notch width index to measure and compare intercondylar notch width. The purpose of this prospective study was to establish a normal range for the notch width index and to correlate intercondylar notch size and anterior cruciate ligament injuries. We gathered data on 902 high school athletes, including range of motion, thigh girth, ligament stability and intercondylar notch width using the notch width index. The population was then followed prospectively and anterior cruciate ligament injuries were recorded and correlated with notch width index in a blind manner. Two-year results showed that the overall anterior cruciate ligament injury rate was 3%. The normal intercondylar notch ratio was 0.231 +/- 0.044. Intercondylar notch width index for men was larger than that for women. Athletes sustaining noncontact anterior cruciate ligament tears have statistically significant intercondylar notch stenosis (notch width index, 0.189). Ten of 14 athletes with noncontact anterior cruciate ligament injuries had a notch width index that was at least 1 SD below the mean. Athletes with contact anterior cruciate ligament injuries had a mean of 0.233. We conclude that athletes with a stenotic intercondylar notch are at significantly greater risk for sustaining noncontact anterior cruciate ligament injury. PMID- 8368415 TI - Cell survival after transplantation of fresh meniscal allografts. DNA probe analysis in a goat model. AB - Fibrochondrocytes synthesize and maintain the extracellular matrix responsible for the distinctive material and structural properties of a normal meniscus. Viable meniscal cells are believed to be necessary for the long-term maintenance of these properties in meniscal allografts. The purpose of this study was to determine if the donor cells (fibrochondrocytes) survive after a fresh meniscal allograft transplantation. A DNA probe technique was used to clearly distinguish the DNA patterns in donor cells from the host cells in the Spanish goat. No remaining donor DNA could be demonstrated at 4 weeks in transplanted meniscal tissue; it was all of host origin. The host DNA content at 4 weeks approached or exceeded the amount present in the contralateral control meniscus. CLINICAL SIGNIFICANCE: The results of this study demonstrate that viable cells in medial meniscal allografts transplanted from one animal to another do not survive. Host cells rapidly repopulate the transplanted meniscus. There is no evidence these new cells will maintain on a long-term basis the extracellular matrix of the meniscus. The evidence in this paper, that the fibrochondrocytes do not survive transplantation, suggests further justification is necessary for using grafts with living cells. Allografts with living cells have an increased expense, more complicated surgical logistics, and have a higher potential risk of disease transmission. PMID- 8368416 TI - Prospective study of osseous, articular, and meniscal lesions in recent anterior cruciate ligament tears by magnetic resonance imaging and arthroscopy. AB - Fifty-four patients with anterior cruciate ligament tears that were arthroscopically reconstructed within 3 months of initial injury were prospectively evaluated. Patients with grade 3 medial collateral ligament, lateral collateral ligament, or posterior cruciate ligament tears were excluded. Eighty percent of our patients had a bone bruise present on the magnetic resonance image, with 68% in the lateral femoral condyle. Two of the latter findings--an abnormal articular cartilage signal (P = 0.02) and a thin and impacted subchondral bone (P = 0.03)--had a significant relationship with injury to the overlying articular cartilage. Meniscal tears were found in 56% of the lateral menisci and 37% of the medial menisci. A significant association was present between bone bruising on the lateral femoral condyle and the lateral tibial plateau (P = 0.02). Results of our study support the concept that the common mechanism of injury to the anterior cruciate ligament involves severe anterior subluxation with impaction of the posterior tibia on the anterior femur. Determination of the significance of bone bruising, articular cartilage injury, or meniscal tears will require a long-term followup that includes evaluation for arthritis, stability, and function. These 54 patients represent the first cohort evaluated in this ongoing prospective clinical study. PMID- 8368417 TI - Arthroscopic treatment of symptomatic extension block complicating anterior cruciate ligament reconstruction. AB - Arthrofibrosis resulting in loss of knee extension compromises the results of anterior cruciate ligament reconstructions. We designed a study to clarify the symptoms and to evaluate the results of arthroscopic treatment of this complication. Forty-two patients in a series of 959 consecutive open anterior cruciate ligament reconstructions required further surgical treatment for relief of symptoms related to loss of extension. Arthroscopic examination of these knees confirmed the presence of an extension block caused by hypertrophy of the ligament or abundant tissue formation in the anterior tibiofemoral joint an average of 9 months after anterior cruciate ligament reconstruction. The offending tissues were excised arthroscopically and the patients were followed with an aggressive rehabilitation program. Thirty-five patients were available for followup an average of 28 months after excision of the tissue. Subjective functional status and symptomatic status were scored numerically using identical, patient-completed questionnaires before and after the excision procedure. Range of motion, Cybex, and KT-1000 arthrometer results were also recorded. The results were statistically compared with results from a control group demographically matched and selected at random from the 959 patients. Before excision of the offending tissue, the knee scores of the study group differed significantly from those of the control group. However, after the excision procedure, the knee scores of the 2 groups were nearly identical. Marked improvements in function and symptoms (most notably, activity-related anterior knee pain, crepitus at terminal extension, and knee stiffness) were noted in all patients in the study group after removal of the extension block and resumption of an accelerated rehabilitation program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368418 TI - Anatomic considerations in harvesting the semitendinosus and gracilis tendons and a technique of harvest. AB - Although the semitendinosus and gracilis tendons have long been used in ligamentous reconstruction procedures of the knee, their anatomic relationships have not been explicitly detailed. Therefore, cadaveric dissections were performed on fresh-frozen adult knees to examine these relationships. Several key anatomic points are useful in the harvest of these tendons. Their conjoined insertion site is medial and distal to the tibial tubercle. They become distinct structures at a point that is farther medial and slightly proximal. Tendon harvest is facilitated by identifying the tendons proximal to this point. The superficial medial collateral ligament lies deep to the tendons in this area and should not be disturbed. The tendons are ensheathed in a dense fascial layer that may impede tendon stripping. The accessory insertion of the semitendinosus tendon (which was present in 77% of the knees dissected) should be identified and transected to avoid tendon damage at harvest. Knee flexion may reduce the risk of injury to the saphenous nerve as it crosses the gracilis tendon. Variation in tendon diameter affects graft strength. PMID- 8368419 TI - Effect of anterior cruciate ligament graft tensioning direction, magnitude, and flexion angle on knee biomechanics. AB - The objective of this study was to determine the biomechanical effect of graft tensioning during reconstruction of the anterior cruciate ligament. We evaluated the magnitude of the tensioning force (22 or 67 N), the flexion angle at which the tension was applied (extension or 30 degrees of flexion), and the direction of application of the tensioning force (proximal, distal, or distal with a posterior force simultaneously applied to the tibia) on 10 fresh cadaveric knees. The anterior cruciate ligament was reconstructed using a bone-patellar tendon bone graft. The graft was then temporarily fixed during the application of each of 12 combinations of tensioning variables listed above. After each fixation, graft force and joint motion were measured during anterior tibial loads. Tensioning direction and the flexion angle significantly affected graft force and joint motion, while the magnitude of the graft tensioning did not. Graft forces were greater when the tensioning was applied at 30 degrees of flexion. Compared with distal tensioning with and without posterior tibial force, graft forces with proximal tensioning were greater in extension and lower in flexion. The position of the tibia relative to the femur was posterior and externally rotated, compared with normal, for all combinations of tensioning variables in both unloaded and anterior load states. PMID- 8368421 TI - Ballet injuries. An analysis of epidemiology and financial outcome. AB - The financial outcome and epidemiology of ballet dancers' injuries were studied by examining workers' compensation insurance records covering 3 seasons (3 years) of activity for a large professional ballet company. One hundred four dancers sustained 309 injuries that resulted in insurance payouts for medical costs of $398,396. The average cost per injury was $1289. Although only 4.2% of the injuries resulted in medical costs exceeding $5000, these represented 60.0% of the total medical costs. Nine injuries resulted in medical costs in excess of $10,000 each. Overall, there were 2.97 injuries per injured dancer. Twenty-four dancers (23.0% of the injured) sustained 5 or more injuries each and thus were responsible for 51.9% (161) of all injuries. The foot (74 injuries, 23.9%), lumbar spine (71, 23.0%), and ankle (41, 13.3%) were the most frequently injured anatomic regions. The experience of this ballet company is similar to that of a college athletic department or a professional sports team. All could employ similar strategies to reduce injuries and associated costs. PMID- 8368420 TI - High- versus low-top shoes for the prevention of ankle sprains in basketball players. A prospective randomized study. AB - Using a prospective, randomized experimental design, 622 college intramural basketball players were stratified by a previous history of ankle sprains to wear a new pair of either high-top, high-top with inflatable air chambers, or low-top basketball shoes during all games for a complete season. Subjects were asked to complete a history questionnaire and were given a complete ankle examination. They were allowed to wear these shoes only during basketball competition. Followed over the course of a 2-month intramural season, 15 ankle injuries occurred during 39,302 minutes of player-time: 7 in high-top shoes, 4 in low-top shoes, and 4 in high-top shoes with inflatable air chambers. The injury rates (injuries per player-minute) were 4.80 x 10(-4) in high-top shoes, 4.06 x 10(-4) in low-top shoes, and 2.69 x 10(-4) in high-top shoes with inflatable air chambers. There was no significant difference among these 3 groups, leading to the conclusion that there is no strong relationship between shoe type and ankle sprains. PMID- 8368422 TI - Overuse ballet injury of the base of the second metatarsal. A diagnostic problem. AB - Performing classical ballet may cause major stress to the feet of the dancer. A variety of foot injuries have been described, with one such injury being an overuse syndrome involving the base of the second metatarsal and adjacent Lisfranc's joint. The diagnosis for this syndrome usually requires differentiating synovitis of Lisfranc's joint from a stress reaction of the base of the second metatarsal. Prompt diagnosis is important since the treatment for these two conditions differs significantly and, in the case of bone stress reaction, delay can cause progression of the lesion. We report good clinical results in a group of eight ballerinas for whom we obtained early diagnosis and treatment of their injuries. This is in contrast to poor results reported in the literature if the diagnosis and management of these types of injuries are delayed. We developed a simple diagnostic protocol to enable diagnosis at presentation. When a bone stress reaction had progressed to a fracture line, a characteristic appearance was found on magnetic resonance imaging, suggesting a specific mechanism of injury. A possible mechanism for this injury is discussed. PMID- 8368423 TI - Anterior shoulder instability in weight lifters. AB - Occult instability is recognized as a major cause of shoulder dysfunction in throwing athletes. Few studies have characterized the findings of occult instability in nonthrowers. The purpose of this study was to examine shoulder instability in a group of weight lifters. The symptoms, physical findings, and results of treatment for 23 shoulders in 20 athletes are presented. All athletes presented with a complaint of progressive inability to perform exercises with the upper extremity in the abducted, externally rotated position (the "at-risk" position) because of pain. One hundred percent of the athletes experienced posterior shoulder pain when the shoulder was placed in forced abduction and external rotation. Thirteen shoulders in 10 patients responded to conservative management including aggressive rehabilitation and modification of technique to avoid the at-risk position. The other 10 shoulders, which did not respond to conservative treatment, required surgical treatment to alleviate the symptoms. All 20 patients have successfully returned to their previous weight lifting activities. PMID- 8368424 TI - Prospective evaluation of the McMurray test. AB - The accuracy and interexaminer reliability of the McMurray test for the diagnosis of meniscal tears were compared with arthroscopic findings in a prospective study of 104 consecutive patients awaiting elective arthroscopy. The only significant McMurray sign found to correlate with meniscal injury was a "thud" elicited on the medial joint line with a medial meniscal tear (P = 0.05) that had a fair interexaminer reliability (kappa = 0.35). The sensitivity of a medial thud was 16%, and the specificity was 98% with a positive predictive value of 83%. Examiner experience had little effect on the accuracy of diagnosis of medial meniscal tears. This study supports the continued but limited emphasis on the McMurray test in the clinical diagnosis of meniscal tears. PMID- 8368425 TI - Quantitative evaluation after arthroscopic anterior cruciate ligament reconstruction. Allograft versus autograft. AB - We measured the anteroposterior ligamentous laxity and thigh muscle power in 92 subjects who were rated as successes after they had undergone arthroscopic anterior cruciate ligament reconstruction for unilateral anterior cruciate ligament insufficiency 18 to 36 months previously. The subjects were divided into 2 groups according to the type of graft: fresh-frozen allogenic tendon (N = 47) or central one third of the ipsilateral patellar tendon (N = 45). Instrumented drawer tests in the Lachman position were performed to measure anterior tibial displacement at 200 N (anterior laxity). Thigh muscle power was isokinetically measured with a Cybex II dynamometer. Significantly more anterior laxity was found in the reconstructed knees than in the contralateral normal knees regardless of graft material (paired t-test, P < 0.01), except for the male allograft patients. Although the mean anterior laxity difference between sides for the allograft patients was less than that for the autogenous ones, analysis of variance failed to demonstrate a statistically significant difference between the 2 groups if the comparison was strictly made within the same sex. Thigh muscle tests revealed that extension torque in the reconstructed knees was significantly less than that in the contralateral knees and analysis of variance showed that knee extension torque at 60 deg/sec for the allograft patients was significantly better than that of the autograft ones (P < 0.05). We concluded that the allograft procedure is advantageous over the patellar tendon autograft in terms of better restoration of anterior stability. PMID- 8368426 TI - Tibiofibular synostosis in professional basketball players. PMID- 8368427 TI - Pneumoperitoneum as a complication of carbon dioxide knee arthroscopy. A case report. PMID- 8368428 TI - Unrecognized Achilles tendon rupture associated with ipsilateral medial malleolar fracture. PMID- 8368429 TI - Comparison of closed and open kinetic chain exercise in the anterior cruciate ligament-deficient knee. PMID- 8368430 TI - Comparison of closed and open kinetic chain exercise in the anterior cruciate ligament-deficient knee. PMID- 8368431 TI - Thoracic spine fracture in a football player. PMID- 8368432 TI - Does needle-exchange save lives? PMID- 8368433 TI - Identification of multiple proliferative growth factors in breast cyst fluid. AB - Gross cystic disease is a common benign breast disease that is associated with a twofold to fourfold increase in breast cancer risk. Both diseases are hormonally induced and may share a common biochemical environment conducive to abnormal proliferative responses. A large collection of breast cyst fluid samples was analyzed for growth factors associated with cell proliferation: epidermal growth factor (EGF), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), platelet-derived growth factor (PDGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta (TGF-beta). The data demonstrate that significant amounts of proliferative growth factors are present in breast cyst fluid of all cyst subtypes. The presence of IGF-II, PDGF, and TGF-beta in breast cyst fluid was confirmed for the first time. EGF, PDGF, and TGF-beta concentrations in breast cyst fluid were several times greater than reported for serum; IGF-I and IGF-II concentrations were several times lower. In the first 100 samples tested, no TGF-alpha was detected. Only EGF and IGF-II levels demonstrated a consistent correlation with apocrine type 1 cysts. These results demonstrated that effective concentrations of proliferative growth factors are in breast cyst fluid and suggest that adjacent breast tissue may be a probable source of synthesis. Growth factor profiles of breast cyst fluid may indicate the presence in breast tissue of a hormonal and proliferative environment permissive to subsequent cancer growth. PMID- 8368434 TI - Comparison of APACHE II, Trauma Score, and Injury Severity Score as predictors of outcome in critically injured trauma patients. AB - Trauma Score (TS), APACHE II score, and Injury Severity Score (ISS) have been utilized to quantitate severity of illness in various groups of patients. The purpose of this study was to compare the relationship of the APACHE II score, TS, and "computer-derived" ISS with outcome in critically injured trauma patients. Data were recorded prospectively in a computer database for 428 consecutive trauma admissions. Stepwise discriminate analysis was utilized to determine the best predictor of both intensive care unit (ICU) and hospital outcome. Forty-two patients died in the ICU (10%), and another 18 patients died after leaving the ICU (4%), for a total mortality rate of 14%. The mean p value and partial R2 value obtained from stepwise discriminant analysis of the relationships between APACHE II score, TS, and ISS to ICU and hospital survival are shown. APACHE II score was the best predictor of both ICU and hospital outcome in these critically ill trauma patients. However, when combining all three measures (APACHE II score, TS, and ISS), only a portion of the variance in outcome is explained by the scores (R2 < 0.05). We conclude that scoring systems for outcome prediction should be utilized only as an adjunct to clinical assessment in the evaluation of the severity of illness and mortality risk in critically ill trauma patients. PMID- 8368435 TI - Portal endotoxin and cytokine responses during abdominal aortic surgery. AB - Interleukin-6 (IL-6) is a major marker of tissue injury. Surgery induces a systemic IL-6 response related to the magnitude of the operation. An exaggerated IL-6 response is associated with the development of major complications after aortic aneurysm repair. Endotoxemia is a potent stimulus for cytokine release and may occur during aortic surgery. This study attempted to examine whether the observed IL-6 response during abdominal aortic surgery is related to the development of portal endotoxemia. Serial samples of inferior mesenteric and systemic venous blood were obtained before, during, and after aortic cross clamping in eight patients undergoing elective aortic aneurysm surgery. Portal endotoxemia was detected in only five of the eight patients during the surgery, and there was no correlation with the IL-6 response. Both portal and systemic IL 6 levels rose during the course of surgery, but, by the time of abdominal wound closure, the mean portal IL-6 levels were eight times higher than the systemic IL 6 levels. These results suggest that the portal circulation draining the colon is a major source of the previously observed systemic IL-6 response to aortic surgery. The IL-6 response is not clearly related to portal endotoxemia but may reflect occult cellular injury in the colon occurring during surgery. PMID- 8368436 TI - Prediction of the severity of acute pancreatitis. AB - We conducted a prospective study to validate our previous finding that serum urea and plasma glucose levels on admission could predict the outcome of acute pancreatitis. Forty-two (24%) of 176 patients developed complications related to the attack of acute pancreatitis and were classified as having severe disease. By logistic regression analysis of 17 admission parameters, serum urea and plasma glucose levels were again the factors with independent significance in defining the outcome. By adopting the same cutoff levels as in our previous study (serum urea level greater than 7.4 mmol/L and plasma glucose level greater than 11.0 mmol/L), and the presence of either factor above the cutoff level as indicative of severe disease, the sensitivity of prediction was 79%, specificity 67%, and overall accuracy 70%. All the deaths were correctly predicted by this urea/glucose criteria. The overall accuracy was also found to be comparable with those of the APACHE II (cutoff level greater than 11) and Ranson's scoring systems. We conclude that the simple prognostic criteria for acute pancreatitis were validated; these criteria have the potential to stratify risk rapidly at the time of admission for patients who might benefit from an aggressive interventional protocol. PMID- 8368437 TI - Selective shunts in selected older cirrhotic patients with variceal hemorrhage. AB - Whereas portal systemic shunts pose significant problems in many patients, they have long been thought to have particular risks when undertaken in older cirrhotic patients, with devastating encephalopathy reportedly common in older patients undergoing nonselective shunt surgery. With advances in anesthesia management and perioperative monitoring and the advent of selective shunting, we postulated that both the operative and long-term outcomes might be improved. In this context, we reviewed our recent experience with selective shunts [distal splenorenal (DSRS) and small-diameter interposition portacaval grafts (IPCG)] in patients over the age of 60 years with variceal bleeding. Nineteen consecutive cirrhotic patients over 60 years of age undergoing elective or urgent selective shunt surgery for variceal hemorrhage since 1986 were identified. Sixteen patients underwent DSRS, and 3 underwent IPCG. The etiologies of the cirrhosis were multiple, with 12 of 19 classified as Child's B or C disease. There were no operative deaths, and all but one patient returned home following the surgery. No patient has had recurrent bleeding or required further surgery for portal hypertension-related problems. Three of 19 developed encephalopathy, and 4 of 19 died of liver failure within 1 year of surgery. Of the 14 patients still alive and well (mean postoperative survival: 44 months, range: 4 to 74 months), all remain free of encephalopathy and live independently. Based on this experience, it would appear that one can anticipate satisfactory short- and long-term outcomes after selective shunt surgery in selected patients with variceal bleeding over the age of 60 years. These patients with portal hypertension should not, therefore, be rejected for shunt surgery based on age alone. PMID- 8368438 TI - Mastectomy with and without immediate breast reconstruction using a musculocutaneous flap. AB - We compared surgical cosmetic results in 83 patients who underwent mastectomy with immediate breast reconstruction (MIBR) using a myocutaneous flap with those of 153 patients with breast cancer who underwent mastectomy without breast reconstruction. Cosmetic results were significantly better in patients who underwent MIBR than radical mastectomy or extended MIBR, although no intergroup difference existed in the reconstructive technique. Neither did any difference exist in the incidence of complications between patients undergoing MIBR and mastectomy without breast reconstruction, or between patients undergoing modified mastectomy and radical or extended mastectomy. Finally, MIBR did not appear to adversely effect recurrence or overall survival. We conclude that MIBR using a myocutaneous flap is an acceptable treatment option for patients with breast cancer. PMID- 8368439 TI - Immunotoxins and recombinant toxins in the treatment of solid carcinomas. AB - Cancer remains the second most common cause of death in our society, and advanced disease is often refractory to surgical, chemotherapeutic, and radiologic interventions. One novel approach to cancer treatment involves targeting a cytotoxic agent to a cancer cell. Immunotoxins have been developed that contain a potent toxin (either Pseudomonas exotoxin, ricin toxin, or diphtheria toxin) coupled to a targeting moiety that directs the molecule to cells expressing a certain antigen. Chemically coupled immunotoxins have been developed over the past 12 years. These bind to and kill cells expressing many tumor-associated antigens. Initial clinical results were disappointing, but recent results have been more promising. Furthermore, newer immunotoxins have been developed that will soon be in clinical trials. Some of these are recombinant toxins that have been developed using techniques of genetic engineering. Transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-1, interleukin-2, interleukin-4, interleukin-6, the binding portions of monoclonal antibodies, and CD4 have been used to direct toxins to cancer cells or cells infected with the human immunodeficiency virus type 1. Efforts are under way to circumvent problems such as immunogenicity that may limit the clinical usefulness of immunotoxins. PMID- 8368440 TI - Parathyroid localization prior to primary exploration. AB - The success of parathyroid surgery is based on accurate localization of normal and abnormal parathyroid glands, knowledge of the pathologic conditions, and meticulous dissection during removal of the abnormal glands. Although parathyroid localization is essential in cases requiring re-exploration, there is considerable controversy regarding the indications for localization studies prior to primary exploration, since the success rate for surgery exceeds 90% to 95%. However, in specific circumstances, including diagnostic problems, technical considerations, and high-risk patient factors, preoperative parathyroid localization assists the operating surgeon even during the primary cervical exploration. The purpose of this paper is to define these specific circumstances and discuss the appropriate studies. PMID- 8368441 TI - Clinical skills acquired during third-year surgical clerkships. AB - An instrument was developed to survey third-year medical students about their experience with 18 clinical skills that are generally recognized as required learning for the third-year surgical clerkship. The same instrument was adapted to ascertain which surgical skills 25 fourth-year medical students, 25 surgical residents, and 25 practicing surgeons thought should be acquired during the third year surgical clerkship. None of these evaluators had completed medical school or residency at our institution. A remarkable degree of conformity was found in the rankings of the 18 clinical skills by senior students, surgical residents, and practicing surgeons; fourth-year students rated only central venous line placement and simple operative procedures as significantly more important than did more senior evaluators. The third-year medical students' actual surgical clerkship experience with 10 out of the 18 skills was significantly below the overall competency levels desired by the graduate groups. Our survey demonstrates that both students and graduates attach similar importance to the acquisition of clinical skills in the third-year surgical curriculum. The instrument utilized in this study to measure students' experience and satisfaction with this phase of their education was reliable, the measurements were consistent, and this information was useful in the evaluation and modification of the curriculum. PMID- 8368442 TI - Laparoscopic cholecystectomy in patients admitted with acute biliary symptoms. AB - Laparoscopic cholecystectomy has become the standard of care for the elective management of cholelithiasis. Little information exists, however, regarding the appropriateness of this procedure in the setting of acute symptomatology. We retrospectively reviewed our experience with 516 laparoscopic cholecystectomies performed at a single institution from May 1990 to May 1991. Seventy-five (14.5%) of these patients were admitted from the emergency department with acute abdominal pain (100%), fever (4 of 75, 5%), and/or an elevated white blood cell count (22 of 75, 29%). There were 54 females and 21 males, with a mean age of 50.0 +/- 2.4 years (range: 17 to 89 years). Laparoscopic cholecystectomy was attempted in all patients, and was successful in 68 of 75 patients (91%). Seven procedures were converted to open cholecystectomy because of the difficulty in dissection precluding safe laparoscopic cholecystectomy. The time from admission to surgery (mean: 3.4 +/- 0.3 days), as well as the total hospital stay (mean: 5.5 +/- 0.6 days), was much longer than in the elective circumstance. Mean laboratory values for the group as a whole were as follows: white blood cell count (mean: 9.6 IU/L +/- 0.4 IU/L, range: 4.1 IU/L to 19.5 IU/L), alkaline phosphatase (mean: 97.0 IU/L +/- 13.7 IU/L, range: 27 IU/L to 375 IU/L), and alanine aminotransferase (mean: 78.3 IU/L +/- 13.7 IU/L, range: 15 IU/L to 701 IU/L). Patients requiring open cholecystectomy were older (mean: 61.4 +/- 4.4 versus 48.8 +/- 2.6), were more likely to be febrile (3 of 7, 42%, versus 1 of 68, 1%), and were more likely to have a significant leukocytosis (mean: white blood cell count 12.9 +/- 1.8 x 10(3) cells/mm3 versus 9.2 +/- 0.4 x 10(3) cells/mm3) than were those undergoing successful laparoscopic cholecystectomy. Laparoscopic cholecystectomy can be performed safely in the majority of patients presenting with acute biliary symptoms. Patients with a triad of acute abdominal pain, fever, and elevated white blood cell count, particularly elderly patients, are more likely to require conversion to open cholecystectomy, however. PMID- 8368443 TI - A new technique of prosthetic arteriovenous fistula construction that eliminates the need for temporary access. AB - The use of polytetrafluoroethylene (PTFE) for hemodialysis requires a maturation period to allow for tissue ingrowth around the graft. If hemodialysis is necessary during this waiting period, then temporary access is used. Unfortunately, temporary access is difficult, if not impossible, to establish in many patients undergoing chronic hemodialysis. We describe a technique for the construction of a prosthetic arteriovenous fistula that eliminates the waiting period and the need for temporary access in selected patients who require PTFE fistulas for hemodialysis. PMID- 8368444 TI - Rescue of failed forearm arteriovenous access grafts using an externally supported polytetrafluoroethylene graft. AB - Thrombosis of the forearm arteriovenous access graft is common. Graft failure usually occurs at the venous anastomosis. Thrombectomy with jump extension to a more proximal unobstructed vein is recommended. A polytetrafluoroethylene graft with externally supported rings across the elbow joint has been used as the extension conduit in eight patients over the past 18 months. Satisfactory prolongation of graft patency for 6 months or more was achieved in seven of these eight patients. PMID- 8368445 TI - Impaired bacterial killing in early obstructive jaundice. AB - Sprague-Dawley rats were challenged with intraperitoneal injection of 10(7) Streptococcus pneumoniae 10 days after common duct ligation (BDL) or sham celiotomy (SC). Quantitative bacterial cultures were performed on liver, spleen, lung, kidney, and heart blood samples obtained 4 hours after injection. All 13 (100%) BDL animals had positive heart blood cultures, but only 6 of 12 (50%) SC animals remained bacteremic (p < 0.05). Significantly more viable organisms were recovered from lung, liver, spleen, and kidney of BDL animals compared with SC controls. BDL impaired the host's ability to kill this encapsulated gram-positive organism. Viable bacteria remained in all organs studied, which was associated with continuing bacteremia. PMID- 8368446 TI - Carcinoembryonic antigen assay of intra-abdominal fine-needle aspirates. AB - Differentiating abscesses from necrotic tumors has important therapeutic implications. Currently, cytologic examination is the "gold standard," but it has a low sensitivity for cystic/necrotic tumors. To address this problem, a prospective study was conducted comparing the results of cytologic examination with those of carcinoembryonic antigen (CEA) immunoassay of fine-needle aspirates in 24 patients undergoing radiologically or surgically guided fine-needle aspiration. Of 26 fine-needle aspirates, 20 were malignant and 6 benign. Final results were correlated with pathologic examination (when available), clinical review, and follow-up. Three patients had an abscess associated with perforated, recurrent carcinoma, of whom only one had cytologic assessment prior to drainage. The sensitivity of fine-needle aspiration was 85%, and for adenocarcinoma alone, 80%. CEA sensitivity (greater than 5 ng/mL) was 50%, and for adenocarcinoma, 90%; the specificity of the assay was 64%. A high CEA level alone was diagnostic of metastatic carcinoma of the colon in two fine-needle aspirates. Cytologic assessment and CEA assay of fine-needle aspirates and cyst/abscess drainage facilitate the diagnosis of unsuspected adenocarcinoma. PMID- 8368447 TI - EDTA chelation therapy. PMID- 8368448 TI - Morbidity after abdomino-perineal resection. PMID- 8368449 TI - Dialysis access. PMID- 8368450 TI - Injuries to the portal triad. PMID- 8368451 TI - Salvaging the functioning graft. PMID- 8368452 TI - Budd-Chiari syndrome. PMID- 8368453 TI - Guanine--an adequate index of mite exposure? PMID- 8368454 TI - Does guanine concentration in house-dust samples reflect house-dust mite exposure? AB - Using specific ELISA extracts, we analyzed samples of pure mite cultures and house dust for group I allergens from Dermatophagoides pteronyssinus, D. farinae, and D. microceras. Correspondingly, we measured the concentration of guanine and xanthine by rigorous chemical methods. The pure mite cultures were used to correlate allergen levels with guanine levels. The house-dust samples one-sidedly contained more guanine than expected. This suggests that considerable amounts of guanine originate from non-house-dust mite sources and implies that guanine quantifications are of limited clinical value. PMID- 8368455 TI - Prediction of mite allergen levels by guanine measurements in house-dust samples. AB - We studied the sensitivity and specificity of guanine environmental tests in the evaluation of the two mite allergen levels, i.e. 2 micrograms/g and 10 micrograms/g of Der p I and Der f I, considered to be risk factors for sensitization or for the development of acute asthma. We examined 239 house-dust samples for Der p I and Der f I levels (ELISA) and guanine contents (semiquantitative guanine test and quantitative assays). All house-dust samples with class 2 or 3 guanine tests contained more than 2 micrograms/g of Der p I and Der f I. The probability that house-dust samples of class 2 contained more than 10 micrograms/g of mite allergens was 88%; it was 100% for house-dust samples of class 3. The probability that a house-dust sample of class 0 contained less than 2 micrograms/g of mite allergen was 87%. For each level of mite allergen, a ROC curve was constructed with the true positive rates and the false positive rates calculated by different cutoffs of guanine concentration. The cutoff point which gave the best compromise between sensitivity (76%) and specificity (89%) was 2100 micrograms/g for the threshold of 2 micrograms/g of Der p I and Der f I. For detection of a mite allergen > 10 micrograms, a guanine content of 3000 micrograms/g gave the best compromise between sensitivity (86%) and specificity (93%). In conclusion, the guanine test represents a satisfactory environmental test, inexpensive and simple, for predicting mite allergen levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368456 TI - The effect of oral drugs on the cytologic picture of nasal mucosa in hay fever. AB - The aim of the present study was to assess the influence of H1-antihistamine and sympathomimetic drugs given orally on cytologic smears of the nasal mucosa. Thirty-five patients with hay fever evaluated cytologic smears of the nasal mucosa before and after a 2-week treatment. Fourteen patients received chlorpheniramine with phenylephrine, 10 patients dexchlorpheniramine, and 11 patients pseudoephedrine. The investigated drugs significantly changed nasal cytograms. The number of eosinophils increased after chlorpheniramine with phenylephrine and after pseudoephedrine but decreased after dexchlorpheniramine. Thus, the sympathetic nervous system stimulation seems to produce local eosinophilia on the nasal mucosa. In view of such a significant correlation between hay fever symptoms and the number of eosinophils in the cytograms, it can be concluded that the combination of antihistamine and sympathomimetic drugs may adversely affect the course of the disease. Although, at the initial stage of the treatment, sympathomimetics reduce swelling and improve the patency of the nose through decongestion of the blood vessels, their negative effect can influence the immunologic mechanisms. PMID- 8368457 TI - Facial thermography during nasal provocation tests with histamine and allergen. AB - Changes of skin temperature (T degree) of the nose area during nasal provocation tests with histamine and allergen were followed by means of an infrared thermography camera. By a colimator system in which temperatures measured on a given surface can be integrated and averaged, thermography allows the continuous and quantitative recording of the temperature during the whole procedure in a completely noninvasive way. In 10 normal subjects, increasing doses of histamine induced a dose-dependent rise of the nose external temperature. No significant change was observed with the vehicle solution. In six subjects allergic to grass pollen, the nebulization of increasing concentrations of a pollen extract induced a dose-dependent rise in T degree. The T degree rise observed after histamine or allergen corresponded to a marked nasal obstruction. The nebulization of the highest dose of the pollen extract did not induce any T degree rise in six nonallergic subjects. The continuous recording of the skin temperature by a noninvasive method might yield additional information on the vascular changes rapidly occurring during nasal challenges. PMID- 8368458 TI - Can subjects with a positive allergen skin test be selected by a short questionnaire? The Glostrup Allergy Study, Denmark. AB - The objective was to evaluate a postal questionnaire screening procedure for selection of subjects with positive reactions to skin prick tests with common allergens. The project consisted of a screening, with subsequent skin prick test of two selected groups. The setting was the Glostrup Population Studies institute in Copenhagen, Denmark. Participants in the screening included 8000 subjects, aged 15-69 years. The subjects were randomly selected from the population of western Copenhagen County, Denmark. From the 6998 respondents (87.5%), 793 subjects were randomly selected (Random Group), and 788 subjects were chosen on the basis of their answers to the questionnaire (Symptom Group). Both groups were invited to take skin prick tests. Attendance rates were 75.5% (Random Group) and 80.6% (Symptom Group). The main outcome measures were responses (yes or no) to the specific questions and the subjects' skin reaction (positive or negative). The association between symptoms and skin reactivity, adjusted for the effects of sex and age, was summarized by odds ratios. Symptoms on exposure to allergens were highly associated with positive skin reactivity. In the Symptom Group the percentage of subjects with at least one positive skin reaction was 57.7%, which was twice as much (28.4%) as in the Random Group. The results show that it was possible to select a group with high skin reactivity on the basis of the symptoms reported in the screening. Questions about exposure to allergens were the most appropriate for selection of this group. PMID- 8368459 TI - Prevention of pollen rhinitis symptoms: comparison of fluticasone propionate aqueous nasal spray and disodium cromoglycate aqueous nasal spray. A multicenter, double-blind, double-dummy, parallel-group study. AB - Fluticasone propionate aqueous spray, a new intranasal corticosteroid preparation, and disodium cromoglycate 2% aqueous nasal spray, an established preventive treatment for seasonal allergic rhinitis, were compared in a double blind, double-dummy, parallel-group, multicentric study in France. A total of 218 patients with seasonal allergic rhinitis caused by grass pollen (verified by positive skin prick test) were preventively treated before the onset of the grass pollen season with either fluticasone propionate 200 micrograms once daily or disodium cromoglycate 5.2 mg four times daily. Half of these doses was given in each nostril. Treatment started before the onset of the pollen season in most patients (178/218). Diary cards, including symptoms of rhinitis and usage of nasal sprays, were filled in twice daily for 6 weeks. Terfenadine in 60-mg tablets and eye-drops could be used as rescue medications. We treated 110 patients with fluticasone propionate and 108 patients with disodium cromoglycate. Patients treated with fluticasone propionate had significantly more days free of primary efficacy symptoms of sneezing (P < 0.001) and nasal discharge during the day (P = 0.002), as well as free of all the other nasal symptoms (P < 0.01), and significantly lower median scores (P < 0.05) for all nasal symptoms except nasal discharge than patients treated with disodium cromoglycate. There was no difference in eye symptoms or in rescue medication use between the two groups. Compliance with the treatment was assessed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368460 TI - Pulmonary function changes in asthmatics associated with low-level SO2 and NO2 air pollution, weather, and medicine intake. An 8-month prospective study analyzed by neural networks. AB - This paper presents the response in subjects with asthma to gaseous air-pollution levels, weather, and medicine intake as identified by principal-component analysis and neural network techniques. Pulmonary function measured by respiratory peak-flow rate in nonallergic asthmatics was associated with ambient, low-level, air-pollution concentrations of sulfur dioxide and nitrogen dioxide, temperature, relative humidity, and medicine intake. Results from 27 nonallergic asthmatics aged 18-60 years with well-characterized bronchial asthma and regular medical treatment were analyzed from two cities. During an 8-month period, each subject kept a diary table, which included symptoms, lung function (evening peak flow), medicine intake, and tobacco smoking. High intake of medicine and high ambient temperatures corresponded to decreased peak flow. The changes in temperature did not occur in situations with low medicine intake. During frost periods, peak-flow values decreased independently of medicine intake and levels of SO2. During other times, increased levels of SO2 and NO2 increased temperature, and increased intake of medicine, and low relative humidity corresponded to decreased peak flow. Increased levels of SO2 and NO2 corresponded synergistically to decreased peak flow at levels above 40 micrograms/m3. PMID- 8368461 TI - In vitro diagnosis of farmers' IgE-mediated allergy by Phadiatop and three new multiallergen RAST analyses. AB - Identification of persons with atopic allergy in a population is difficult if the pattern of sensitizing allergens is unique. Three new multiallergen tests, Professional Allergy Mixes (PAX) 1-3 (Pharmacia Diagnostics, Uppsala, Sweden), have recently been introduced to screen IgE-mediated allergy among farmers. PAX 1 contains animal danders and feathers, PAX 2 mites and insects, and PAX 3 pollens and molds. The value of these new tests for the determination of IgE-mediated allergy among farmers was compared with that of Phadiatop, a test for general atopy. Of 440 farmers, 91 were positive to Phadiatop and 97 to any of PAX 1-3. None of the farmers were positive in all tests. Only 70/97 sera positive in RAST to PAX 1-3 had a positive Phadiatop, whereas of 91 sera positive in Phadiatop, 70 had specific IgE antibodies to PAX 1-3. The value of using either Phadiatop or PAX 1-3 is limited (sensitivity 74-79%), but, together, these four tests will detect almost all (95.9%) farmers with IgE-mediated sensitization and all (100%) with symptoms. We have also shown that the grain weevil Sitophilus granarius and the botfly Gasterophilus intestinalis are important sources of allergens in rural environments. PMID- 8368463 TI - Regional distribution of asthma-related hospital treatment periods in Finland in 1972-86. AB - We examined the use of asthma-related hospital services in geographically different areas of Finland in 1972-86, using data obtained from hospital discharge registers. A total of 254,402 cases diagnosed as asthma was identified (diagnosis 493, International Classification of Diseases, 8th Revision), information on the patient's place of residence enabling comparison of the southern, western, eastern, and northern parts of the country. Annual hospitalizations and the occurrence of new cases were calculated relative to the population, the former being found to increase throughout the country during the period studied, the most marked rise being 8.8% in Northern Finland (95% confidence interval 6.4-11.3%), and the smallest, 1.1%, in Western Finland (-0.2 to +2.5). A corresponding trend was also noted in the annual occurrence of new cases, which increased most in Northern Finland, i.e. by 4.8% (3.0-6.6), and decreased in Western Finland by 2.9% (-3.6 to -2.1). The change in asthma and the organization of treatment and factors related to the cold environment may, in combination, contribute to difficulties in the treatment of asthma in Northern Finland. PMID- 8368462 TI - Occupational protein contact dermatitis from herring. AB - We present a case of occupational protein contact dermatitis caused by herring in a dolphinarium worker. The in vivo and in vitro tests results indicated a type I allergic mechanism. In vivo cross-reactivity among fish belonging to the Clupeiformes order was observed. PMID- 8368464 TI - A comparison of the efficacy of cetirizine and terfenadine. A double-blind, controlled study of chronic idiopathic urticaria. AB - In a 20-d, double-blind, randomized, parallel study, the efficacy of cetirizine and terfenadine was compared in 30 patients with chronic idiopathic urticaria. Subjects were randomly divided into two 15-patient groups. The first group was given cetirizine (10 mg once daily); the second terfenadine (60 mg twice daily). Cetirizine proved to be more effective than terfenadine in controlling urticaria symptoms. In fact, the score of the investigators' overall assessment was significantly lower in the cetirizine-treated group than in the terfenadine treated group. Moreover, patient evaluation by a visual analog scale and symptoms assessed on a 4-point scale showed a better improvement in the cetirizine group. The number and severity of side-effects were similar in both treatment groups. PMID- 8368465 TI - Localized periorbital edema induced by aspirin. AB - We documented localized periorbital edema in two patients with aspirin sensitivity without underlying chronic urticaria. The reaction developed 30 min after ingestion of 62.5 and 125 mg of aspirin, respectively. No systemic symptoms were observed. Other NSAIDs did not induce symptoms. These patients were able to tolerate doses of aspirin after pretreatment with terfenadine. These observations suggest that histamine plays a central role in aspirin-induced skin reaction. Despite the fact that terfenadine blocks the drug-induced reaction, this protocol should be used with caution and only where there is no feasible alternative to aspirin. PMID- 8368466 TI - The batch-to-batch variation of the potency of dog- and cat-allergen-coated lancets. Evaluation by skin prick testing. AB - In clinical work I formed the impression that the potency of Phazet lancets, for cat and dog allergens, was lower than earlier and too low to diagnose all clinically sensitive children with cat and dog allergy. Therefore, I decided to investigate the potency of newly produced and several years old Phazet lancets coated with dog and cat allergens. Twenty-six adults with case histories of cat and/or dog allergy and skin reactive to extracts of either dog dander or cat epithelium were skin prick tested in duplicate with one old batch and one newly produced batch of Phazet dog and/or cat lancets as well as the in-house reference of cat and/or dog allergen, 100,000 BU/ml. The potency of Phazet lancets in relation to the standard was evaluated by the median slope of the allergen dose response relationship. The potency of the old dog lancets (mean 48,900 BU/ml) was higher (NS) than that of the newly produced lancets (mean 28,000 BU/ml), and the potency of both types of lancets was significantly less (P < 0.001) than that of the dog allergen in-house standard. On the other hand, the potency of newly produced (123,000 BU/ml), but not old (108,000), cat-allergen-coated Phazet lancets was higher than that of the cat allergen in-house reference extract (P = 0.048). There was a marked variation in potency between patients. Most of this variation was due to factors varying between patients, not between lancets, indicating that the composition of the allergen on the lancets was partly different from that of the standard.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368467 TI - Human proteins in house dust. PMID- 8368468 TI - Anaphylactic reaction to ranitidine. AB - Ranitidine is a well-tolerated H2-receptor antagonist with a furan ring as nucleus. Anaphylactic reactions are seldom reported despite the wide use of the drug. We report a patient who presented an anaphylactic reaction with ranitidine (Zantac). The positive skin prick test and oral challenge suggest type I hypersensitivity. Specific IgE determination by RAST technique and histamine release test with ranitidine were negative. The patient did not react to other H2 receptor antagonists or to another furan-derivative (nitrofurantoin). PMID- 8368469 TI - Cross-reactivity between quinolones. Report of three cases. AB - Cross-reactivity between quinolones is uncertain. Recently, we studied three patients who had developed suspected allergic reactions to a quinolone. For all of them we performed skin test, histamine release test, RAST, and oral provocation with the suspected quinolone and also with another quinolone of the opposite generation. Five atopic and five nonatopic subjects were used as controls. Neither skin test, histamine release test, nor RAST was useful in the diagnosis. By means of oral controlled provocation, the reactions were reproduced, and all the patients also reacted to another quinolone. We concluded that cross-reactivity between quinolones seems to be very important, and avoidance of any quinolone should be recommended to any patient who has suffered an allergic reaction to one of these drugs. PMID- 8368470 TI - [Routine postoperative epidural analgesia. X-ray control of epidural catheter position and prevention of the spread of epidural contrast media]. AB - In the last few years epidural analgesia with bupivacaine and/or opioids has become an important technique in the therapy of postoperative pain. Using bupivacaine only 2-20% of the patients are treated without sufficient success. To ascertain and evaluate the underlying reasons for this, we prospectively investigated 51 patients routinely, and 6 patients with an insufficient analgetic effect from a group of 212 patients, by means of epidurography. All patients were treated mainly with bupivacaine. The observed and documented radiographic data were compared with the individual analgetic results. METHODS. All investigations were performed within 24 h after placing the catheters. The contrast agent was injected under radiographic guidance in two different positions, and the end of the distribution was documented in the anterior-posterior ray path. In group I (n = 26) the catheter position and the distribution of the contrast medium with 3.0 ml iopamidol were documented. In group II (n = 25) the catheter position was documented in the same way, but the distribution was documented for the stepwise injected contrast medium (3.0 ml + 2.0 ml + 3.0 ml). As a result of these findings we changed our epidural catheter placement concept in the following patients (group III, n = 212), and performed radiographic examinations in patients with a therapy failure only (group IIIa, n = 6). Instead of placing the catheter postoperatively mostly lumbal in a lateral position, we now placed them preoperatively, in the sitting position, as near as possible to the centre of the segments to be treated. RESULTS. Only 27 patients demonstrated an ideal catheter position and a typical contrast medium distribution. Three of these patients still could not be treated successfully. In 12 patients the spread of the contrast medium was inhomogeneous, and in 5 patients the contrast medium was found on one side of the epidural space only. Half of these 17 patients (n = 9) needed supplementary therapy. Surprisingly, 4 of 8 patients with a paraepidural catheter position were treated with success. DISCUSSION. Effective bupivacaine therapy by epidural catheter injections constitutes no striking evidence for a correct epidural catheter position. If the catheter lies in the epidural space, the actual therapeutic effect of bupivacaine therapy is determined mainly by the distribution of the substance. The epidural position of the catheter--central or lateral in the epidural space--seems, however, not to be particularly important. If high-quality analgesia is to be achieved with bupivacaine alone, or in combination with an opioid, the catheter should usually be placed near to, or better into the centre of the segments to be treated. The results demonstrate that in the case of failure of epidural catheter therapy, epidurographic examinations are very helpful in ascertaining and evaluating the underlying reasons for this failure and in coming to a logical decision for changing the concept. PMID- 8368471 TI - [The effect of different autotransfusion procedures on the antibiotic picture. A study on cephalosporin cefamandole]. AB - Infection after open heart surgery is a serious complication since eradication of infection in these cases is difficult even with appropriate antibiotic therapy. In the attempt to avoid this problem, prophylactic administration of antibiotics is common. Their relative safety and their broad spectrum of activity make cephalosporin antibiotics popular choices for prophylaxis prior to and during operations, including cardiovascular procedures. METHODS. Preoperative antibiotic prophylaxis with 2 g cefamandole was performed in a prospective randomized study including 62 male patients divided into three groups. All patients gave informed consent, and the study was approved by the ethics committee of the hospital. Patients in group 1 (n = 21) and group 2 (n = 21) underwent aortocoronary bypass (ACVB) with extracorporeal circulation (ECC), while patients in group 3 (n = 20) had carotid surgery. Anaesthesia, coronary-bypass procedures and infusion regime were standardized. The flow rate during ECC was maintained at 2.41/min/m2 and the rectal temperature between 33 degrees and 34 degrees C. Arterial and urine specimens for the determination of plasma and urine levels of cefamandole were taken at definite times. Autologous blood salvage during operation was performed with haemofiltration techniques (HF) in group 1 (HF 80, Fresenius, Bad Homburg, Germany) and with cell separation techniques (CS) in group 2 (Hemonetics III, Hemonetics). Plasma and urine cefamandole levels were measured by high-pressure liquid chromatography (HPLC). RESULTS. After administration of 2 g cefamandole mean peak levels of 404.6 +/- 141.7 micrograms/ml were seen. Because of haemodilution at the beginning of extracorporeal circulation, group 1 and 2 showed much lower cefamandole plasma levels, 22.1 +/- 11.6 micrograms/ml and 24.3 +/- 14.4 micrograms/ml, than group 3 (after the same time course), with 47.4 +/- 19.1 micrograms/ml. For all patients in group 1 and 2 prebypass time (70.3 +/- 22.4 min) and the duration of the ECC (72.3 +/- 17.7 min) were comparable. There was a significant correlation between prebypass time and cefamandole plasma levels at the beginning of extracorporeal circulation (P < 0.001). No correlation could be seen for the plasma concentration after discontinuation of the extracorporeal circulation and the duration of extracorporeal circulation. The volume of autologous red packed cells and the enclosed amount of cefamandole showed a significant difference (P < 0.001) between group 1 (1120.0 +/- 296.8 ml, 27.5 +/- 17.1 mg) and group 2 (734.3 +/- 186.6 ml, 2.9 +/- 3.2 mg). The plasma cefamandole level after transfusion of autologous blood displayed a significant correlation (p < 0.01) with cefamandole concentration in the autologous red packed cells. Transfusion of the autologous blood produced no significant increase in plasma cefamandole levels. With an operation time of more than 2.5 h during ECC the cefamandole plasma level decreased below the necessary minimal inhibitory concentration (MIC90), particularly for gram-negative bacteria. CONCLUSION. Additional administration of 1 g cefamandole shortly before the beginning of cardiopulmonary bypass is recommended, particularly for surgical procedures with ECC of more than 2.5 h. Adjustment of drug dosage prior to or during surgery may be required to optimize therapy, but before this can be achieved precisely, more information on drug disposition during the operative procedures is needed. PMID- 8368472 TI - [The potential dependence of the effect of bupivacaine and ropivacaine on the heart. In-vitro studies on the effect of local anesthetics on the force of contraction and the action potential in left guinea pig atria]. AB - The cardiotoxicity of long acting local anaesthetics is still a matter of controversy. Therefore, the effects of bupivacaine and ropivacaine on cardiac contractility and electrophysiologic parameters were evaluated in the presence of different extracellular potassium concentrations. METHODS. In strips from left atria of guinea pigs action potentials were induced to obtain cumulative dose response curves for bupivacaine (racemic mixture) and ropivacaine (S-enantiomer). Effects on force of contraction and parameters of the action potential (especially maximum upstroke velocity, dV/dtmax, as an indirect measure of fast sodium channel function) were compared for low (2.7 mM) and high (8.7 mM) extracellular K+ concentrations (n = 7-8). RESULTS. At low K+ concentration, bupivacaine and ropivacaine depressed force of contraction and dV/dtmax in a dose dependent manner. At higher local anaesthetic concentrations, action potential amplitude decreased and action potential duration was prolonged. There was no influence on the resting membrane potential (Tables 2, 3). At high K+ concentration, both local anaesthetics induced effects similar to those observed with low K+, but the dose-response curves for contractility and dV/dtmax were shifted leftward. The EC50 of bupivacaine for the negative inotropic effect and, analogously, for dV/dtmax was approximately 10 times lower. Similar results were observed for ropivacaine (Figs. 1, 2). CONCLUSION. This study confirms the dependence of the cardiodepressive effects of bupivacaine on the extracellular K+ concentration (i.e. membrane potential). The present investigation shows a similar dependence for the effects of ropivacaine, a new long-lasting local anaesthetic. Our results concerning the potential dependency of dV/dtmax depression are compatible with the binding of bupivacaine to the inactivated state of the sodium channel protein preferentially (modulated receptor hypothesis). Thus accumulation of block will occur if stimulation frequency is in an appropriate range. Though we found striking analogies between potential dependency of dV/dtmax depression and negative inotropic effect, there is no firm evidence that the sodium channel block by bupivacaine or ropivacaine substantially participates in the latter effect. An influence on other ionic channels such as the calcium channel remains to be evaluated. PMID- 8368473 TI - [The neuropathy of the autonomic nervous system. An additional anesthetic risk in diabetes mellitus]. AB - Some 20-40% of diabetics suffer from an autonomic neuropathy. This complication of diabetes mellitus impairs the regulation and the reflexes of the cardiovascular system. This study compares the cardiovascular characteristics of diabetics and nondiabetic control patients. METHODS. 21 patients (11 diabetics, 10 nondiabetics) undergoing ophthalmic surgery were investigated. They were tested preoperatively for autonomic cardiovascular dysfunction by application of four established tests. These were: heart rate responses to the Valsalva maneuver, deep breathing and standing up (30/15 test) and the Schellong test. The anaesthesia was induced with fentanyl (0.1 mg), etomidate (2.5 mg/kg) and succinyl choline (1.5 mg) and maintained with oxygen/nitrous oxide (1.4:3 l/min) and isoflurane (0.2-0.8 vol%). Blood pressure and heart rate were automatically measured every minute during induction of anaesthesia and every 3 min during anaesthesia. Additionally the heart rate response to 0.5 mg atropine i.v. was evaluated. RESULTS. The autonomic function tests revealed pathologic reactions in all diabetics (two early, six definitive, three severe) and none in controls. Remarkable cardiovascular events occurred exclusively in the diabetic group, especially during induction of anaesthesia. The systolic blood pressure (SAP) increased in diabetics from a preinduction value of 150 mmHg (median, range 105 205 mmHg) to a maximum of 200 mmHg (160-250 mmHg) after intubation, in controls from 130 (100-150 mmHg) to 170 (110-190 mmHg). Following this peak, SAP fell in diabetics to 120 mmHg (80-160 mmHg), in controls to 110 (100-140 mmHg). Two diabetics had to be treated because of an SAP exceeding 220 mmHg, two other diabetics because of an SAP below 80 mmHg. After atropine administration the heart rate of diabetics showed a median increase of 15% (range 0-40%). In four diabetics, however, the increase was less than 10%. In control patients the increase was 50% (40-80%). All patients with severe cardiovascular reactions during induction of anaesthesia and with heart rate elevation following atropine of less than 10% had a definite or severe neuropathy of the autonomic nervous system revealed by the tests. DISCUSSION. In the only slightly stressful ophthalmic surgery, remarkable events were noted particularly during the induction of anaesthesia. The critical decreases and increases of SAP might be related to the autonomic dysfunction, because of the hypersensitivity of a partly damaged autonomic nervous system or its impaired function. This led to a loss of heart rate variation and adequate blood vessel tone. The severe cardiovascular reactions always went along with clearly pathologic findings in the tests performed. Normal test results in diabetics implied normal cardiovascular reactions, as could be observed in nondiabetics. CONCLUSION. Abnormal cardiovascular reactions in diabetics must be kept in mind. The simple tests specified here can identify such predisposed patients. PMID- 8368474 TI - [Computer-aided anesthesia monitoring. Experiences with the use of three systems in heart surgery]. AB - Basic monitoring in cardiac anaesthesia embraces at least 19 different parameters of haemodynamics and blood gas analysis. In special cases additional measurements may be desirable, providing a total of up to 44 variables displayed on various monitors, as depicted in Fig. 2. The recording of such an amount of data is only feasible with automated recording systems. Therefore, in the past 6 years we have introduced three different computer systems to our cardiac anaesthesia workplaces. The experiences in their handling are reported. MATERIAL AND METHOD. Three systems were investigated: (1) System S 4000 (Siemens, Germany), based on a central processor unit (PDP 11, DEC, Japan) connected with 20 bedside input/output terminals and Sirecust 404a monitors (Siemens). The system collected the data in a ring buffer with a capacity for about 24-48 h. (2) Patient Care Manager (PCM; Siemens, Germany), a single workplace system based on an IBM compatible personal computer (PC) with the operating system environment DOS 5.0/Windows 3.0. In our test configuration it was connected with a Sirecust 1281 monitor (Siemens). (3) Monitor-Data-Manager (MDM) (our own development). This single workplace system is also based on an IBM-compatible PC running under DOS and was connected to four different monitors used in our cardiac surgery operating theatre (Fig. 2). A second computer (Sirecust S 425, Siemens) served as an interface between the two 404 monitors (not featuring a serial output like RS 232) and the PC. The self-developed program for that interface was memory resistant and executable with three key presses when the anaesthetic record was started. The three systems were compared with regard to their ease of use, function and practicability. RESULTS. System S 4000: Because of the older system architecture, the response time to key inputs was fairly long and the menu structure somewhat uncomfortable. A major drawback was the limited data buffer capacity and the lack of a long-term storage medium as well as the lack of compatibility with the industry standard for PCs. Software interfaces to other companies' monitors were not implemented, limiting the system to the Sirecust 404 devices. Patient-Care-Manager: The user interface is a Windows 3.0 application representing an up-to-date graphical environment. Unfortunately some Windows features were not fully used, e.g. the free positioning and sizing of graphic windows and the color options. Drug inputs were somewhat long-winded, limiting the system's suitability for the operating theatre. The main disadvantage, however, was the lack of interfaces to monitors other than those from Siemens. Monitor Data Manager: The system was designed to sample data from all monitors operating in our hospital's heart surgery department. Each parameter was displayed in a digital form to get close control over the recorded data (Fig. 1b); additionally calculated values like total peripheral resistance or oxygen demand could be drawn from a separate window. Furthermore, key inputs were reduced to minimum, making drug inputs faster than the hand-written protocol. The ease of performing calculations of continuous drug infusions (from microgram/kg/min to ml/h pump speed) was particularly appreciated by the users. Since the data were saved as an ASCII file, they could easily be imported by any spreadsheet like Lotus 1-2-3 or Excel, providing the whole variety of their graphical presentation or calculation features. Because of the high sampling rate (3 min), even short-lasting drug effects could be registered, making the system favourable for scientific studies. CONCLUSION. Automated monitor data record systems are considered to be a prerequisite not only for research in anaesthesia but also for quality assurance. A basic requirement for wide acceptance in clinical practice is a user interface that provides fast and convenient key inputs as well as further information about parameters not displayed on other monitors. In our h PMID- 8368475 TI - [Radiologic position control of epidural catheters (epidurography). An instrument of quality assurance for regional analgesia]. AB - Epidural analgesia is a very efficient method of postoperative pain management. Nevertheless, problems such as unilateral analgesia, sensory loss and inadequate pain relief are often difficult to handle. Radiologic evaluation of the position of the catheter and the spread of radiopaque dye (epidurography) is an important advance toward a solution of these problems. METHODS. The findings of 110 consecutive epidurographies from the acute pain service of the Department of Anaesthesiology of the University Hospital of Kiel, Germany, were analysed. Radiograms were obtained following the injection of 2 ml and an additional 8 ml of radiopaque dye (iopamidol) in the anterior-posterior and lateral plane. In addition, typical and instructive examples of epidurographies from the past 8 years are presented. RESULTS. In 99 of 110 patients the epidurography revealed a proper position of the catheter. Seven cases of partial displacement (e.g. paravertebral spread of radiopaque dye) and two cases of complete misplacement were documented. Allergic reactions or other side effects were not observed. The radiologic criteria for a proper epidural position of the catheter are discussed (Fig. 2a). Furthermore, examples of the following malpositions of epidural catheters are presented: intravascular misplacement (Fig. 2b), paravertebral misplacement (Fig. 2c), paravertebral escape of radiopaque dye (Fig. 2e) and correct distribution after the catheter had been withdrawn 2 cm (Fig. 2f), intrathecal misplacement (Fig. 2g), and simultaneous spread of dye in the subarachnoid and epidural space in a patient with preceding dural tap (Fig. 2h). In some cases unexpected reasons for problems in postoperative pain management were revealed by epidurography (e.g. disc prolapse, (Fig. 2d). CONCLUSION. In our view epidurography is a valuable way of improving the quality and safety of postoperative epidural analgesia. It is an important tool for decision-making in the event of clinical problems. The benefits for the patients have to be weighed against the radiation exposure. PMID- 8368476 TI - [Morphine tablets for chronic non-tumor-induced pain. Which factors modify the success or failure of a long-term therapy?]. AB - In a prospective study 60 patients receiving morphine for treatment of mostly neuropathic and musculoskeletal pain of non-malignant origin were investigated. The aim of the study was to determine the characteristics of responders to morphine therapy and the frequency and severity of side effects. METHODS. Eligible patients suffered from chronic pain that had not been relieved despite all current therapy. All of them received controlled-release morphine tablets. Dose was increased in case of insufficient pain relief. Before morphine treatment and at the follow-ups pain intensity was rated on a numeric analogous scale, analgesia and side effects on a four-stage verbal rating scale. Intake of the prescribed and other drugs was randomly controlled by urine analysis. The patients were divided in three groups retrospectively: group I, non-responders who ceased the morphine therapy within 1 month due to weak analgesia or severe side effects; group II, patients in whom the therapy was stopped within the following months despite persisting pain; group III, patients who continued therapy. STATISTICS. ANOVA, chi-squared test, non-parametric tests (Kruskal Wallis, Wilcoxon). Results were accepted as significant at p < 0.05. RESULTS. Twenty-three patients were non-responders. Fourteen other patients stopped the therapy after initial response because the side effects exceeded the benefit of analgesia (group II). Only 10 of the remaining 23 responders had good analgesia and minor side effects during the observation time. Constipation, despite prophylactic laxatives, and nausea were the most frequently reported events causing cessation of therapy. Analgesia and side effects in groups II and III were constant during the observation time of 241 (36-1486) days. In groups II and III, 43% of the patients needed an increase of the morphine dosage during therapy. The initially sufficient morphine dosage was significantly higher in group II than in group III; only one patient needed more than 90 mg/day in group III. Urine screening tests in 45 patients disclosed that 18 patients concealed the intake of other opioids or psychotropic drugs, mostly benzodiazepines. CONCLUSIONS. The study showed many problems with the patients' compliance and acceptance of oral morphine due to side effects and lack of analgesia. The discrepancy from other, positive reports might be explained by the extremely selected patients of this study and by the fact that not only responders were included for evaluation. Patients' compliance seems to have been overestimated in previous studies because no urinary controls were taken. PMID- 8368477 TI - [Epidural spinal cord stimulation in therapy-resistant angina pectoris]. AB - Spinal cord stimulation (SCS) has routinely been used since the beginning of the 1970s. The initial indications for stimulation were the so-called deafferentation or neurogenic pain. Further work has confirmed that neurostimulation is useful in severe peripheral vascular disease in relieving pain and increasing capillary blood flow and oxygen tension. The effects are similar to those of sympathectomy. In 1964 Apthorp et al. discovered that sympathectomy relieved angina in about 75% of patients. The use of SCS to treat angina follows logically from its use in peripheral vascular disease. METHODS. The pain-relieving effect of SCS was investigated in two patients, 54 and 69 years old, who were hospitalised for 8 and 28 days. Both patients had severe angina pectoris (duration 2 and 15 years, New York Heart Association class III and II), related to three-vessel disease, and one of them had previously undergone his third bypass operation. The other patient was not considered suitable for surgery. The antianginal treatment (long acting nitrates, beta-blockers, calcium antagonists) was regarded as optimal and was not changed during the observation period (Table 1). SURGICAL TECHNIQUE AND STIMULATION EQUIPMENT. We used the commercially available Medtronic SCS system. The operation was performed under local anaesthesia to allow the patient to answer questions during the intraoperative stimulation. The epidural space was punctured at the level of T7-T8 in one case and T11-T12 in the other. The electrode tip was positioned in the midline or a few millimetres to the left at the T1-T2 level (Figs. 1, 2), so that the patient felt a prickling sensation in the precordial area and into the arms. The distal end of the electrode was sutured to the fascia and connected via a tunnelled extension lead to the external pulse generator. The pulse width was 200 microseconds, frequency 80 Hz. An appropriate amplitude (usually 8-10 V) was used for comfortable paraesthesia. The study consisted of two parts: a run-in period (1 week) to standardise the stimulation when mobilisation was performed. A treatment period (18 months) to determine the patient's working capacity after continuous stimulation (Table 2). After a successful run-in period a Medtronic receiver was implanted, connected to the electrode and stimulated by external pulse generator. Different variables were used to assess the effect: pulse rate, blood pressure, the product of pulse rate and systolic blood pressure, estimated anginal pain, and ST changes in the electrocardiogram (ECG) before, during and after mobilisation. RESULTS. The stimulation was carried out for 30 min 10-12 times a day during the run-in period and five to six times a day during the treatment period. Altogether there was slight lowering of heart rate and systolic blood pressure. Consequently the product of heart rate and systolic blood pressure was diminished. In one case (NYHA II) the distinct disorder of repolarisation reverted to the normal condition as shown on ECG. In the other case (NYHA III) the ECG remained unchanged because of a severe aneurysm of the cardiac wall. Both patients experienced nearly complete pain relief after a few days for 6 and 12 months respectively. However, an increasing effort tolerance could be demonstrated in both patients by reducing the extent of the heart failure (NYHA II/III to NYHA I/II) (Table 2). DISCUSSION. Our two hospitalised patients had clinically intractable angina pectoris and severe manifestations of heart disease corresponding to at least NYHA functional class II-III. Both were unsuitable for operation and showed no improvement on individually titrated maximal oral antianginal drug treatment. During SCS treatment significant improvement was obvious: chest pain, ST-segment depression, and the extent of heart failure could be reduced. Both patients reached a better NYHA functional class, exhibited increased working capacity and reported reductions in anginal attacks and pain. Th PMID- 8368478 TI - [Emergency 12-hour transesophageal stimulation in a 21-month-old infant]. AB - In a 21-month-old child with complex cyanotic congenital heart disease an aortopulmonary shunt was created as preparation for a modified Fontan operation. During the early postoperative period low cardiac output with right atrial pressures of 20 mm Hg developed due to a slow ventricular tachycardia (ventricular rate 135 bpm). Pharmacological interventions (isoprenaline 0.01 mg/kg hourly and lidocaine 1 mg/kg hourly were without any effect. As epicardial pacing leads had not been implanted during surgery, atrial pacing was performed via the transoesophageal route using a 9.5-F bipolar electrode catheter with an interelectrode distance of 15 mm. Atrial capture could be established with an impulse width of 9.9 ms and 10 mA output at a rate of 150 bpm. With restoration of atrioventricular synchronicity, right atrial pressure finally decreased to 10 mm Hg with consecutive stabilization of the cardiovascular status. After 12.5 h transoesophageal pacing could be stopped without any problems due to spontaneous cessation of ventricular tachycardia. No clinical signs of oesophageal injury were noted. It is concluded that transoesophageal pacing is a practical, safe and effective method for emergency cardiac pacing. PMID- 8368479 TI - [AIDS]. PMID- 8368480 TI - Cycled primer extension: a method for DNA amplification and labeling from templates of unknown sequence. AB - A method has been developed for simultaneous radiolabeling and amplification of DNA hybridization probes. The method is termed cycled primer extension (CPE). CPE is a series of temperature-driven reactions in which template DNA is successively denatured and extended by a thermostable primer-dependent DNA polymerase. The primers consist of semirandom nanomers of the form 5'-NNN NNN (G/C)(G/C)(G/C)-3'. These nanomers have the capacity to anneal to any template DNA and serve as initial anchors for extension at the high temperatures required for Taq DNA polymerase activity. CPE cycles consist of 94 degrees C denaturation, annealing of primers to template upon ramping to 24 degrees C, and gradual extension of the primer along the template as temperature is ramped back to 94 degrees C. Labeling efficiency with [32P]dCTP was examined and optimized as determined by the relation to ratios of radiolabeled to unlabeled dCTP, by number of cycles, and by primer composition and sequence. CPE probes can be generated without regard to size or sequence of template and have a high specific activity (approximately 10(9) dpm/micrograms). With CPE, hybridization signals equivalent to those from random primed probes are routinely obtained with initial template amounts as low as 1 ng. PMID- 8368481 TI - Method for simultaneous detection of protein kinase A, protein kinase C, protein tyrosine kinase, and calmodulin-dependent protein kinase activities. AB - We report a simple method that permits simultaneous detection of multiple protein kinase activities using postnuclear supernatant of v-src transformed NIH3T3 cells. A supernatant is incubated with activators of protein kinases and [gamma 32P]ATP, and the phosphorylated proteins are analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. The method enables detection of activities of at least four protein kinases (protein kinase A, protein kinase C, protein tyrosine kinase(s), and calmodulin-dependent protein kinase III) on a single gel. Experiments using various specific activators and inhibitors of protein kinases indicated that this method can, in crude preparations, reliably detect the protein kinase activities intended for measurement. Protein kinase C activity disappeared when membranes were solubilized, demonstrating the importance of membrane environment for its function. This method should be particularly useful for evaluating and screening protein kinase inhibitors. PMID- 8368482 TI - Activity measurement and multiplicity detection of human secretory-type ribonuclease based on polycytidylic acid/ethidium bromide fluorescence. AB - Two analytical methods for human secretory-type ribonuclease, which are based on polycytidylic acid/ethidium bromide fluorescence, have been developed. The first is a method for measurement of secretory-type ribonuclease activity utilizing the radial diffusion of ribonuclease in a thin agarose gel plate containing polycytidylic acid and ethidium bromide. Ribonuclease activity was visualized as a dark circle on a fluorescent background under ultraviolet light after immersing the gel in a cooled acidic solution. The radius of the dark circle was proportional to the amount of the enzyme. This method allows quantitation of human secretory-type ribonuclease down to at least 5 x 10(-5) unit, which corresponds to 60 pg. Secretory-type ribonuclease activity in 18 different human tissues and body fluids was measured. The second method is a zymogram technique for detection of secretory-type ribonuclease after isoelectric focusing, which includes placing a dried agarose film containing polycytidylic acid and ethidium bromide on the focused gel. Human secretory-type ribonuclease (less than 3 x 10( 4) unit) was detected with a high band resolution on the same principle as that of the activity assay described above. PMID- 8368483 TI - Synthesis and characterization of N-octanoyl-beta-D-glucosylamine, a new surfactant for membrane studies. AB - The new nonionic glycosidic surfactant N-octanoyl-beta-D-glucosylamine (NOGA, molar mass 305.37 g) was synthesized through an easy and efficient two-step procedure. Specifically, beta-D-glucosylamine was obtained by the replacement of the anomeric hydroxyl of D-glucose by an amino group which was then selectively acylated. NOGA was finally purified by silica gel column chromatography and recrystallization. This compound is stable and soluble in water and usual buffers up to 80 mM at 4 degrees C and up to 0.2 M at 37 degrees C. NOGA solutions are also characterized by a low ultraviolet light absorbance above 250 nm (epsilon 280 approximately 1.5 M-1 cm-1). Due to its very high critical micelle concentration (CMC = 80 mM, as determined by spectrofluorimetry), this surfactant may easily be removed from samples by dialysis or, to a lesser extent, by adsorption onto hydrophobic beads. Furthermore, NOGA is colorimetrically titrable by the ninhydrin method and its weak interference in protein determination by the bicinchoninic acid method is easy to overcome. This surfactant exhibits a good solubilizing power toward membrane proteins, with a marked selectivity for spiralin, a bacterial surface antigen. Protein extraction started below the CMC, but was much more effective above this concentration threshold. NADH oxidase activity, ligand binding by the glycine betaine-binding protein, and antigenicity of more than 20 membrane or soluble proteins were not altered by NOGA. Thus, owing to its extraction efficacy and mildness toward protein structure and activity, NOGA should prove useful for membrane studies and offers the additional advantage of being easy to synthesize at low cost. PMID- 8368484 TI - Sulfotransferase and glycosyltransferase analyses using a 96-well filtration plate. AB - Previously, we identified and characterized a sulfotransferase responsible for the 4-O-sulfation of Asn-linked oligosaccharides terminating with the sequence GalNAc beta 1,4GlcNAc beta 1,2Man alpha (GGnM). Here we present a rapid and sensitive method to assay for this sulfotransferase which is significantly more convenient than existing procedures. The acceptor substrate in this assay is human transferrin (Tfn) which has been enzymatically modified such that its N linked oligosaccharides bear the terminal sequence GGnM. GGnM-Tfn is biotinylated, and a fluid-phase transferase reaction is done which utilizes [35S]3'-phosphoadenosine 5'-phosphosulfate ([35S]PAPS) as the sulfate donor. The reaction product [35S]SGGnM-Tfn-biotin is separated from unreacted [35S]PAPS and radiolabeled endogenous acceptors by capture onto avidin immobilized onto a PVDF based 96-well filtration plate. Sulfate incorporation in this assay is linear with respect both to the donor and to the acceptor substrates and is also dependent upon enzyme input and time. With this assay, we can detect as little as 0.1 pmol of sulfate transfer. In addition, by using asialo-Tfn-biotin as an acceptor and [3H]CMP-sialic acid as a donor substrate, we demonstrate that this assay can be modified for use with the alpha2,6-sialyltransferase. PMID- 8368485 TI - Method for sequencing synthetic oligodeoxynucleotide phosphorothioates. AB - Sequencing of oligodeoxynucleotide phosphorothioate by a modified Sanger method of sequencing is described. The procedure involves ligation of synthetic oligodeoxynucleotide phosphorothioate to an oligodeoxynucleotide, referred to here as "helper oligonucleotide." The helper oligonucleotide has a region which is complementary to T7 primer. By using DNA polymerase and nucleoside triphosphate mixture, 5'-labeled T7 primer is extended onto ligated oligodeoxynucleotide phosphorothioate, which is then analyzed on gel electrophoresis. PMID- 8368486 TI - Reversibility of cysteine labeling by 4-(aminosulfonyl)-7-fluoro-2,1,3 benzoxadiazole. AB - The fluorescent cysteine derivative formed upon alkylation of proteins with 4 (aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (ABD-F) is shown to be unstable under certain conditions. Although previously thought to be an irreversible reaction, the fluorescence and absorbance associated with the ABD-cysteine can be released from the protein by heating at basic pH in the presence of reductants. Reversal of labeling is accelerated by increasing the temperature, pH, and concentration of reductant. Upon reversal of labeling, a free sulfhydryl is regenerated, since the treated protein can subsequently be realkylated (without reductant) to approximately the same level with only ABD-F. The findings reported in this work are relevant to the use of this alkylating reagent prior to any procedure involving heating or long incubation under reducing conditions, including re-electrophoresis or enzymatic deglycosylation. Investigators using ABD-F or structurally similar reagents should be aware that the cysteine derivative formed is not stable under these conditions. The reversal of cysteine derivatization may also be useful as a method for replacing the ABD-cysteine adduct with a label more suitable for subsequent specialized procedures. PMID- 8368487 TI - A 13C NMR study on ibuprofen metabolism in isolated rat liver mitochondria. AB - A 13C NMR approach was taken to study the biotransformation of (R)- and (S)-[2 13C,2-2H]ibuprofen-CoA in isolated rat liver mitochondria. The 13C chemical shift induced by 2H substitution for the C-2 of [2-13C,2-2H]-ibuprofen-CoA is about 0.5 ppm relative to the corresponding 1H-bearing thioester. The C-2 resonances for [2 13C]- and [2-13C,2-2H]ibuprofen-CoA are 5 ppm downfield with respect to their acid counterparts. Consequently, this technique permits real time analyses of the metabolic fate of the doubly labeled substrate in a quantitative manner. The initial rate of the epimerization of (S)-[2-13C,2-2H]ibuprofen-CoA relative to the (R)-counterpart by intact mitochondria was estimated to be 1.5, which is in line with the equilibrium constant determined with the purified epimerase. Contrary to the reports by other groups, this 13C NMR study did not find spontaneous hydrolysis of the CoA-thioester upon being exposed to intact mitochondria. Current focus of this investigation is to extend this NMR methodology to the levels of whole cells and live animals to gain a better understanding of the enantioselective metabolism of ibuprofen. PMID- 8368488 TI - A dependable method for the synthesis of [14C]trehalose. AB - A new method for the preparation of [14C]trehalose was developed, based on the ability of yeast cells to accumulate trehalose under stress. The method is simple and reliable. It utilizes a yeast strain in which the gene that encodes for phosphoglucoisomerase has been deleted. Thus, exogenously supplied glucose is not metabolized, but is instead converted to trehalose. The [14C]-trehalose obtained is pure, it is hydrolyzed by trehalase, and it is not susceptible to the action of alpha-glucosidase. The yield of this method is in the order of 35% of the [14C]glucose supplied. PMID- 8368489 TI - Phase separation of nonionic detergents by salt addition and its application to membrane proteins. AB - By adding salts (sodium chloride, ammonium sulfate), it is possible to induce phase separation in membrane-protein solubilisates containing Triton X-100 or Nonidet P-40 at temperatures between 0 and 20 degrees C. Other nonionic detergents of the Brij, Lubrol, and Tween series can also be used for this procedure. The salt concentration required for induction of phase separation is dependent on the hydrophobicity of the detergent used. For detergents of the Triton series it seems that detergents with lower hydrophilic lipophilic balance numbers need lower salt concentrations to separate the phases than those with larger hydrophilic parts. Ammonium sulfate precipitation as an initial purification step for membrane proteins should be avoided in the presence of the nonionic detergents tested. Instead of this procedure, phase separation induced by sodium chloride or ammonium sulfate can be recommended, as was proved for membrane-bound proteases of Pseudomonas aeruginosa and Bacillus cereus and for bacteriorhodopsin. PMID- 8368491 TI - Voltage gradient electrophoresis of nucleic acids on agarose gels. AB - A very simple method is described which allows the separation of DNA molecules in a wide molecular weight range (from 0.6 to about 30 kb) in the same electrophoresis agarose gel. This is based on the achievement of a voltage gradient through a simple device consisting of a Plexiglas plate placed slantwise with respect to the gel surface plane, submerged in the electrophoretic running buffer. Further applications of our system are also described. PMID- 8368490 TI - Capillary electrophoresis for protein analysis: separation of human growth hormone and human insulin molecular forms. AB - The capillary zone electrophoresis (CZE) technique was evaluated for separation and quantification of human growth hormone (hGH), human insulin (hI), and proinsulin. Three different molecular forms of biosynthetic hGH (20K, 22K, 44K), methionyl-hGH, biosynthetic hI, and proinsulin, were studied. The hormones were separated with uncoated capillaries, and various analytical conditions were tested (different buffers, ionic strength, pH). The samples were introduced both at positive pressure and electrokinetically, and the voltage applied was varied in each case. Linearity, repeatibility, and limit of detection (0.8 microM for hGH and 1.3 microM for insulin) were determined. Different purification steps were tried in order to find a suitable preanalytical procedure for hGH and hI purification from plasma. Recovery rates from 65 to 80% were obtained. PMID- 8368492 TI - Preparation of a cell-free translation system with minimal loss of initiation factor eIF-2/eIF-2B activity. AB - Cell-free translation systems prepared from suspension-cultured HeLa S3 cells or mouse L cells by hypotonic shock followed by Dounce homogenization poorly initiated the translation of exogenous mRNA. In contrast, cell extracts prepared from cells exposed to the detergent lysolecithin translated exogenous mRNA readily. The block in initiation in the former lysates was localized to the ribosome fraction. During in vitro translation polysomes from homogenized cells disaggregated but the run-off ribosomes were unable to reinitiate translation. The block resulted from a decrease in eukaryotic initiation factor 2 (eIF-2) or the guanine nucleotide exchange factor (eIF-2B) activity, since the addition of eIF-2 or eIF-2B to these latter extracts substantially improved the capacity of the extract to initiate translation of exogenous mRNA. Extracts from homogenized cells, but not from detergent-treated cells, showed enhanced ability to phosphorylate the alpha subunit of exogenous eIF-2. We show that the method of cell extract preparation greatly influences the state of eIF-2/eIF-2B activity in the resulting extract and that extracts in which this activity is maintained can readily initiate translation on exogenous mRNA and reinitiate on endogenous mRNA. PMID- 8368493 TI - Electrophoretic techniques for the analysis of synthetic amyloid beta-A4-related peptides. AB - Two electrophoretic techniques have been developed for the analysis of synthetic beta-A4 related peptides. The first is an acetic acid--urea--polyacrylamide gel electrophoresis denaturing system while the second employs capillary zone electrophoresis at pH 7. Both methods were calibrated to identify the state (monomeric or aggregate) of the longer amyloid fragments beta-A4(1-40) and beta A4(1-43) during analysis. PMID- 8368494 TI - An evaluation of five commercial immunoassay data analysis software systems. AB - An evaluation of five commercial software systems used for immunoassay data analysis revealed numerous deficiencies. Often, the utility of statistical output was compromised by poor documentation. Several data sets were run through each system using a four-parameter calibration function, and the results were compared to those from an independent method. Comparable results between systems were obtained, but often several attempts at analysis were necessary. The evaluation process revealed that it is difficult to monitor the numerous options available on these types of programs, and that incorrect results could easily be obtained if comparison analyses were not used. Recommendations for improved software functionality and for using the four-parameter calibration model are presented. PMID- 8368495 TI - A semidry electroblotting system efficiently transfers both high- and low molecular-weight proteins separated by SDS-PAGE. AB - A general procedure is described for the simultaneous recovery by electroblotting on nitrocellulose or polyvinylidene difluoride (PVDF) membranes of both high- and low-molecular-weight proteins already separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It is based on the use of an original set of buffers which creates a stable pH boundary between the two faces of the blotted membrane. The gel to be transferred is placed on the basic side (pH 8.4) of this boundary, which also contains sodium dodecyl sulfate. Under these conditions even the high-molecular-weight proteins are efficiently eluted out of the acrylamide. Their migration is then stopped on the membrane, due to the change of pH with the acid side (pH 3.8) of the boundary, and the presence of methanol in it. This increases the adsorption on the membrane of the low-molecular-weight polypeptides which have a low affinity for nitrocellulose or PVDF. The procedure permits a quantitative transfer of complex samples which contain poorly soluble proteins or with molecular masses outside the range of 20-70 kDa, like grain storage proteins of cereals. PMID- 8368496 TI - Multiple sequence analysis: pool sequencing of synthetic and natural peptide libraries. AB - Sequence analysis by automated Edman degradation has been one of the most powerful tools for the characterization of peptides for many years. Its sensitivity allows experiments in the low picomole range, and its results provide complete information about the primary structure of proteins and peptides. A new method in protein and peptide sequencing has been developed which allows for the direct application of automated Edman degradation to the analysis of peptide mixtures. With the aid of multiple sequence analysis, first, sequence motifs of isolated, naturally processed peptides binding to MHC molecules have been defined. Second, the method proved to be a valuable and reliable tool for the characterization of synthetic peptide libraries, and third, the specificity of proteases has been determined in a fast and efficient way. PMID- 8368498 TI - A nondenaturing preparative gel electrophoresis system for the recovery of functional proteins. Application to the identification of an endogenous protein inhibitor of fucosyl-transferase activities. AB - Electroelution of protein bands resolved by nondenaturing polyacrylamide gel electrophoresis was performed to identify an endogenous protein inhibitor of fucosyltransferase activities, called fuctinin, through its biological activity. After electrophoresis protein bands were negatively stained with zinc acetate, indicating that this staining technique can be also applied to nondenaturing polyacrylamide gels. However, even under appropriate electroelution conditions, a strong fucosyl-transferase inhibitory activity was eluted from the polyacrylamide gel itself that impeded the measure of fuctinin activity. As an alternative to electroelution, collection of proteins resolved by nondenaturing polyacrylamide gel electrophoresis as they are electrophoresed off the end of the gel was assayed. In the commercially available preparative electrophoretic systems, an elution chamber is limited by a semipermeable membrane on which proteins were adsorbed in the low-ionic-strength buffer used in nondenaturing electrophoresis. We demonstrate that the simple and inexpensive electrofractionation system described by Shain et al. (Anal. Biochem. 200, 47-51, 1992) can be successfully applied under nondenaturing conditions to purify and identify fuctinin through its biological activity. However, caution must be taken in the design of the apparatus in order to avoid local heating and thermal denaturation of proteins. The utility of this nondenaturing preparative electrophoresis system for the study of functional proteins is also demonstrated by the recovery of enzymatic activities of alkaline phosphatase and beta-galactosidase. PMID- 8368497 TI - Isoelectric focusing: pH gradients established with simple buffers and a cation selective membrane. AB - A method for isoelectric focusing is presented in which pH gradients are established with simple buffer systems in a thin granulated gel bed. The gel bed is supported by a cation-selective membrane over a buffer-filled channel with a sloping bottom. The component of the electric field parallel to the gel and membrane surfaces that results from this arrangement may be considered fixed at each position in the gel bed but increases with the decreasing depth of the buffer filled channel below. This feature, together with the ion-selective properties of the supporting membrane, allows the electric field to maintain a shallow pH gradient by adjusting the composition of the buffer at each position in the gel bed. Ribonuclease, myoglobin, beta-lactoglobulin, and ovalbumin, representing proteins with a wide distribution of isoelectric points, were focused in the buffers glycine, imidazole, Mes, and acetic acid, respectively. Focused protein fractions were rerun on conventional polyacrylamide-carrier ampholyte gels. PMID- 8368499 TI - Size-dependent separation of proteins denatured in SDS by capillary electrophoresis using a replaceable sieving matrix. AB - The determination of molecular weights by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is one of the most powerful electrophoretic techniques for protein characterization. A separation media has been developed which allows this type of analysis to be performed in the capillary format. A replaceable polymeric solution rather than a polymerized gel was used as the sieving matrix. This solution allowed for the separation of proteins denatured in SDS in a size-dependent manner as demonstrated by the linear correlation between the proteins' relative migration and the concentration of the sieving matrix (Ferguson plot). The logarithm of the molecular weight of protein standards correlated linearly with the relative mobility of the denatured proteins over the molecular weight range of 14,000 to 205,000. The calculated resolution at half peak height was such that proteins that differed by as little as 4% in molecular weight would be resolved. Finally, the integrated peak areas at 215 nm were linearly proportional to the mass of the protein injected. PMID- 8368500 TI - Simultaneous high-performance liquid chromatographic determination of both the cleavage pattern and the stereochemical outcome of the hydrolysis reactions catalyzed by various glycosidases. AB - A high-performance liquid chromatographic method for the simultaneous determination of both the stereochemical outcome and the cleavage pattern of enzymatic action on unmodified sugar substrates is described. Three different enzymes were investigated by this method. Human pancreatic alpha-amylase hydrolyzed maltopentaose with retention of anomeric configuration, with the cleavage position being two glucose units from the reducing end. Cellulomonas fimi endoglucanase D hydrolyzed cellopentaose with retention of anomeric configuration and predominantly two glucose units from the reducing end. beta-D Xylosidase from Butyrivibrio fibrisolvens hydrolyzed o-nitrophenyl beta-D xylopyranoside with inversion of anomeric configuration. PMID- 8368501 TI - Further studies on the lysozyme-like activity of alpha-lactalbumin: development of alternative methods of assay. AB - Earlier, a sensitive turbidimetric method was reported (H.A. McKenzie and F.H. White, Jr. Biochem. Int. 14, 347-356, 1987), with which evidence was found for weak lysozyme-like activity in alpha-lactalbumin (alpha-LA) against Micrococcus luteus. Alternative methods have been developed for the further study of trace cell-lytic activity, and the results are compared with those of the turbidimetric technique. These methods involve (1) determination of weight loss from a suspension of bacterial cells after exposure to the protein under investigation, and (2) viability studies on the exposed cells. In addition, exposed and control cells were subjected to microscopic examination. Results from all studies were consistent with lysis of cells by alpha-LA as well as by lysozyme. Activities of alpha-LA from the three methods of assay, expressed as ratios to those of lysozyme, were 2.2-5.2 x 10(-5) (mean = 3.6 x 10(-5). The methods were assessed with respect to sources of error characteristic of each and to protein dose requirements for a specified level of cell killing. The turbidimetric approach remains useful for measuring cell-lytic activities as described here. However, caution is urged in its general use. PMID- 8368502 TI - Electrochemical preparation of 1,1'-dimethylferricinium from a water-soluble 1,1' dimethylferrocene-2-hydroxypropyl-beta-cyclodextrin complex and its applications in enzyme assay. AB - Water-soluble 2-hydroxypropyl-beta-cyclodextrin (hp-beta-CyD), a cyclic and nonreducing oligosaccharide, was used to enclose the hydrophobic guest molecules ferrocene (FeCp2) and 1,1'-dimethylferrocene (DMFeCp2) to form a water-soluble complex. At high concentrations (300 mM), hp-beta-CyD enclosed up to 100 mM FeCp2 or DMFeCp2. The yellow complexes were electrochemically oxidized (platinum vs Ag/AgCl poised at +450 mV) to form the blue dyes ferricinium (FeCp2+) and 1,1' dimethylferricinium (DMFeCp2+). This is a one-electron transfer process and the ferricinium cations formed exhibited absorption peaks at 620 and 650 nm, respectively. The concentrated DMFeCp2+ was much more stable (4 months) than the FeCp2+ (2 days) and both oxidized dyes were insensitive to a wide pH variation (pH 2-11). The DMFeCp2+ was reduced easily by various reducing agents such as ascorbic acid, uric acid, and sulfite and exhibited an absorption coefficient of 325 cm-1 M-1. Application of the novel DMFeCp2+ complex as a colorimetric dye for the enzymatic oxidation of glucose, glutamate, lactate, phenylalanine, xanthine, and hypoxanthine was successfully demonstrated. When applied to real samples the results obtained agreed well with those of standard enzymatic assays. The DMFeCp2+ complex could also be utilized to monitor activity of oxidases under saturating substrate concentrations. PMID- 8368503 TI - Assay of the human liver citric acid cycle probe phenylacetylglutamine and of phenylacetate in plasma by gas chromatography-mass spectrometry. AB - Phenylacetate, derived from phenylalanine, is converted in human and primate liver to phenylacetylglutamine. The latter has been used to assess the labeling pattern of liver citric acid cycle intermediates. We present gas chromatographic mass spectrometric assays of phenylacetylglutamine, phenylacetate, and phenylalanine in biological fluids. The compounds are derivatized with dimethylformamide dimethyl acetal. Limits of detection are 0.1 nmol for phenylacetylglutamine and phenylacetate and 2 nmol for phenylalanine. Baseline plasma concentrations of phenylacetate and phenylacetylglutamine and 1 and 3 microM, respectively. The 24-h urinary excretions of phenylacetate and phenylacetylglutamine are about 4 mumol and 1 mmol, respectively. Ingestion of phenylalanine (in the form of aspartame) by a human is followed by sequential increases in phenylacetate and phenylacetylglutamine concentrations in plasma and urine. This assay opens the way to noninvasive probing of the 13C-labeling pattern of liver citric acid cycle intermediates in humans. PMID- 8368504 TI - Methods for the quantitation of bromosulfophthalein and its glutathione conjugate in biological fluids. AB - This paper describes a solvent-gradient HPLC method which was developed for the quantitation of bromosulfophthalein (BSP) in erythrocyte and albumin containing (blood) perfusate samples, and of BSP and its glutathione conjugate (BSP-GSH) in bile samples obtained from rat liver perfusion experiments. Phenolphthalein was used as an internal standard. The cysteinyl-, N-acetylcysteinyl-, and cysteinylglycinyl-BSP conjugates did not interfere with the HPLC assay and cysteine, N-acetylcysteine, [3H]GSH, and [3H]GSSG eluted within the first 6 min postinjection onto the HPLC system. A spectrophotometric method was also developed for the rapid quantitation of BSP in blood perfusate; tracer [14C]urea was utilized as the internal standard. Although the spectrophotometric method was less sensitive than the HPLC method, good correlation was found to exist between the methods. PMID- 8368505 TI - pH modification to enhance the molecular sieving properties of sodium dodecyl sulfate-10% polyacrylamide gels. PMID- 8368506 TI - Preferential binding of the carboxylate form of camptothecin by human serum albumin. PMID- 8368507 TI - High-efficiency shotgun cloning of curved DNA segments from chromosomal DNA. PMID- 8368508 TI - Microanalyses of beta-cyclodextrin and glucosyl-beta-cyclodextrin in biological matrices by high-performance liquid chromatography with pulsed amperometric detection. PMID- 8368509 TI - A method for synthesizing genes and cDNAs by the polymerase chain reaction. PMID- 8368510 TI - An ultrasensitive technique for the analysis of glycoproteins using lectin blotting with enhanced chemiluminescence. PMID- 8368511 TI - Mini isoelectric focusing device to be used with the Bio-Rad Mini-Protean II System. PMID- 8368512 TI - Detection of beta-1,3-glucanase activity in gels containing alkali-soluble yeast glucan. PMID- 8368514 TI - A novel combinational pH-PCO2 microelectrode. AB - A novel combinational pH-PCO2 microelectrode based on a neutral carrier hydrogen ion exchanger is described. It is easy to fabricate and allows pH and PCO2 to be measured simultaneously. The microelectrode has a 5-microns tip. The PCO2 microelectrode exhibits a linear response in the range 1.75 x 10(-5)-10(-2) mol/liter with a Nernstian slope of 57.0 mV/decade at 25 degrees C. The detection limit is 10(-5) mol/liter. The pH microelectrode exhibits a linear response in the range pH 4-12 with a Nernstian slope of 60.0 mV/decade at 25 degrees C. The 95% steady-state response time of the PCO2 microelectrode is about 2 min, while it is about 10 s for pH microelectrode. The electromotive force drift is 4.3 mV/h (PCO2) and 2.6 mV/h (pH), respectively. The lifetime is 3 to 4 days. The microelectrode can measure pH and PCO2 in body fluids simultaneously with satisfactory results. It is also a good basic electrode for enzyme microelectrolysis. PMID- 8368513 TI - Separation and size distribution of red blood cells of diverse size, shape, and origin by flow/hyperlayer field-flow fractionation. AB - Red blood cells (RBCs) from human, equine, canine, feline, and bovine whole blood samples have been separated and characterized by high-speed flow/hyperlayer field flow fractionation (Fl/HyFFF). The elution-based separation of RBCs by this method is based mainly on the size and shape of the cell particles. The typical separation time for RBCs is less than 3 min. Size distributions can be derived from the fractograms of cell samples using a calibration plot based on retention data for uniform polystyrene beads. The method is shown to be effective both to separate and to characterize cell populations, including those with cells of abnormal shape and size. In order to investigate differences in cell morphology, shape and size changes induced by 500,000 Da Dextran were monitored. The changes in the Fl/HyFFF elution profiles indicate that the RBCs decrease in size but become partially aggregated in the presence of the dextran. These changes were found to depend on polymer concentration and specific blood samples. Some of the results from Fl/HyFFF were compared with those from the Coulter counter and from microscopy. PMID- 8368515 TI - Detection of iron binding proteins by a blotting technique. AB - We describe a simple method for detecting iron binding proteins based on binding of 59Fe to protein blots from SDS gels followed by autoradiography. This binding is specific and is not affected by other metal ions. The method has allowed identification of new iron binding proteins in intestinal mucosa and in Hela cells. PMID- 8368516 TI - A high throughput fluorogenic substrate for interstitial collagenase (MMP-1) and gelatinase (MMP-9). AB - Two members of the matrix metalloproteinase family of enzymes, interstitial collagenase and 92-kDa gelatinase, have been implicated in the pathogenesis of rheumatoid arthritis and tumor metastasis. In order to characterize the activities of these enzymes, we have developed a fluorogenic peptide substrate which is efficiently hydrolyzed by both enzymes. This substrate was developed based on the addition of the fluorescent tag, N-methyl-anthranilic acid (Nma), to several previously synthesized substrates that had been evaluated with respect to their turnover by interstitial collagenase. One substrate, Dnp-Pro-Cha-Gly Cys(Me)-His-Ala-Lys-(Nma)-NH2, had favorable solubility characteristics, was > 98% quenched, and produced a single cleavage product, Dnp-Pro-Cha-Gly, with a high fluorescence yield with both interstitial collagenase and 92-kDa gelatinase. Since the assay depends on measurement of increases in fluorescence, the position of the Nma group also proved to be important for optimization of the fluorescence signal. The assay is free from interference by organomercurial compounds and the cleavage product has excitation and emission spectra compatible with filters commonly available on commercial plate readers. The assay has been adapted to a 96-well format and provides a rapid screening protocol for the evaluation of inhibitors of these enzymes. PMID- 8368517 TI - A continuous fluorescence displacement assay for phospholipase A2 using albumin and medium chain phospholipid substrates. AB - A continuous fluorescence assay for phospholipase A2 is described which involves the displacement of the highly fluorescent fatty-acid probe 11-(dansylamino) undecanoic acid from albumin by decanoic acid released as a result of phospholipase A2-catalyzed hydrolysis of didecanoyl-phosphatidylcholine. Using the phospholipase A2 from Naja naja, this assay will detect activity from 1 ng of pure enzyme and a linear response in terms of fluorescence change with time is observed up to about 50 ng of enzyme. The assay is compared with the original fluorescence displacement assay (Wilton, D.C., 1990, Biochem. J. 266, 435-439) which uses rat liver fatty acid binding protein instead of albumin and is able to utilize any natural long chain phospholipid as substrate. The present assay will provide a very convenient method for detection during enzyme purification of the low molecular weight secreted phospholipase A2 and other phospholipases A that can hydrolyze medium chain phospholipids. The assay should also allow the identification of inhibitors of these enzymes. Other substrates including dioleoylphosphatidylcholine and 1-stearoyl-2-arachidonoylphosphatidylcholine were also evaluated in the assay. PMID- 8368518 TI - The application of size exclusion chromatography and computer simulation to study the thermodynamic and kinetic parameters for short-lived dissociable protein aggregates. AB - We describe a method to study the monomer-dimer equilibrium of human growth hormone (hGH) making use of a very short size exclusion high-performance liquid chromatographic column and rapid flow rates. By adjusting the flow rate and thus the retention time on the column, the dissociation of the hGH dimer can be observed. Using computer simulation, both the equilibrium constant for dissociation and the dissociation rate constant can be determined directly, followed by the indirect determination of the association rate constant. This method is potentially useful for determining the thermodynamic the kinetic parameters of aggregation of many protein-protein (homodimers and heterodimers) and protein-ligand systems whose rates of interaction are too rapid to be studied by conventional techniques. PMID- 8368519 TI - Quantitative determination of serine proteinase inhibitor activity using a radial diffusion assay. AB - An improved, time efficient, visual assay for quantitative determination of proteinase inhibitor activity in protein extracts is reported. Proteinase inhibitor activity of mammalian, bacterial, and fungal serine proteinases can be quantified. The method relies on radial diffusion of proteinase inhibitor containing extracts from a central well through an agar gel containing a serine proteinase. After an incubation period the agar gel is stained via the diazo coupling of the beta-naphthol produced by the enzymatic hydrolysis of N-acetyl-DL phenylalanine-beta-naphthyl-ester. Circular zones containing inhibitor-proteinase complexes remain colorless while the region containing only proteinase shows a bright pink-purple color. A reference curve relates the diameter of the colorless zone to the logarithm of the proteinase inhibitor concentration. The error in the estimation of a proteinase inhibitor quantity varying between 10 and 1000 pmol is 4-12%. The sensitivity of the assay is approximately 2-20 pmol of inhibited proteinase molecules depending on the inhibitor-proteinase complex assayed. The sensitivity of the assay can be enhanced 10-fold or more by dilution of the proteinase concentration in the agar and by a reduction of the agar thickness. PMID- 8368520 TI - Identification of cysteine residues at the 10-pmol level by carboxamidomethylation of protein bound to sequencer membrane supports. AB - A procedure is described for the in situ carboxamidomethylation of cystine/cysteine residues in protein samples of as little as 10 pmol, prior to automated protein sequence analysis. Previous in situ methods for the modification of cysteines are limited to proteins available in quantities greater than 100 pmol due to contaminants which interfere with HPLC identification of phenylthiohydantoin amino acids, and cannot be performed on polyvinylidenedifluoride (PVDF)-bound samples. In our procedure, protein samples, immobilized on either PVDF- or polybrene-treated glass filters, are reduced with tributylphosphine followed by alkylation with iodoacetamide prior to automated sequence analysis. Carboxamidomethylcysteine is formed in high yield with no discernable side reactions in standard proteins (insulin, human transferrin, lysozyme) or experimental samples. Both initial and repetitive yields of carboxamidomethylated proteins were either comparable to or better than nonalkylated proteins. No apparent increase in background nor any sequence preview due to partial amino-terminal alkylation was observed. The carboxamidomethylation procedure described here successfully overcomes the limitations of available methods for reduction and alkylation of less than 100 pmol of protein directly on sequencer membrane supports. PMID- 8368521 TI - Simultaneous kinetic-based determination of fructose and ascorbate with a rotating bioreactor and amperometric detection: application to the analysis of food samples. AB - A recently introduced biosensor comprising a rotating bioreactor and a stationary platinum ring amperometric detector (Anal. Chem. 1993, 65, 636-639) has been utilized for the simultaneous determination of fructose and ascorbate. The approach has been successfully applied to the simultaneous determination of these analytes in fresh food samples. Hexacyanoferrate(II) is the monitored species at +0.380 V vs a Ag/AgCl, 3 M NaCl reference. The determination takes advantage of a fast chemical oxidation of ascorbate by hexacyanoferrate(III) ions and the subsequent slower production of hexacyanoferrate(II) in the D-fructose 5 dehydrogenase-catalyzed reaction between D-fructose and hexacyanoferrate(III) as acceptor. D-Fructose 5-dehydrogenase (EC 1.1.99.11) was incorporated into the rotating disk reactor in immobilized form and on controlled-pore glass via the glutaraldehyde attachment and cross-linking with bovine serum albumin. Sample/reagent processing was accomplished by programmed continuous-flow/stopped flow/continuous-flow operation. PMID- 8368522 TI - Optical measurements of pH using fluorescence lifetimes and phase-modulation fluorometry. AB - We measured the pH-dependent fluorescence decay times of the seminaphthofluoresceins (SNA-FL), seminaphthorhodafluors (SNARF), and BCE-CF using phase-modulation fluorometry. The phase and modulation values were found to be strongly pH-dependent in the physiological pH range, over the easily accessible range of light modulation frequencies from 10 to 300 MHz, making these probes useful as lifetime-based pH sensors. The phase and modulation values are dependent on excitation and emission wavelength as well as pH. This dependence allows the range of pH sensitivity to be chosen by selection of the wavelength(s) and enables increased precision of the pH measurements by use of phase and/or modulation measurements at several wavelengths. These probes can be excited using a a green He-Ne laser at 543 nm, which allows their use in low cost instrumentation. Phase and modulation measurements are especially suitable for sensing applications because they are insensitive to the changes in signal intensity that result from photobleaching, probe washout, and/or light losses. PMID- 8368523 TI - Simplification of high-energy collision spectra of peptides by amino-terminal derivatization. AB - Four-sector tandem mass spectrometry proves extremely useful for providing sequence information for peptides. The complexity of ion fragmentations, however, makes data interpretation difficult and time consuming. Attachment of a fixed positive charge to the peptide amino terminus forces production of only N terminal fragment ions to yield simplified, predictable fragmentation. Reaction of a peptide at pH 6 with iodoacetic anhydride selectively modifies the N terminus by exploiting the pK(a) differences between the alpha-amino group and any lysine side-chain epsilon-amino groups. The iodoacetyl peptide can react with many reagents to form a fixed positive charge. We find reaction with dimethyloctylamine forms a quaternary ammonium derivative with good surface activity properties and concomitant increased sensitivity. The high-energy CAD fragment ion spectra of the N-terminally derivatized peptides show predominantly a(n) and d(n) ions. The abundant d(n) ions permit ready distinction of leucine and isoleucine. Fewer fragment ions make data interpretation simpler and lead to more intense peaks since the ion intensity is spread among fewer peaks. The method is particularly useful for peptides which do not otherwise yield sufficient fragmentation to provide either the complete sequence or the locations of modified amino acids. PMID- 8368524 TI - Tryptic mapping of recombinant proteins by matrix-assisted laser desorption/ionization mass spectrometry. AB - Various matrix mixtures have been used for matrix-assisted laser desorption/ionization mass spectrometry to characterize the tryptic maps of recombinant human growth hormone (rhGH) and recombinant human tissue plasminogen activator (rt-PA). Carbohydrate-containing comatrices give improved results over single-component matrices. Of those studied, fucose plus 2,5-dihydroxybenzoic acid (DHB) produced a signal for 24 out of 25, or 96%, of the tryptic peptides of rhGH in a single spectrum. These results were obtained for analyses of as little as 280 fmol of unfractionated material measured in digestion buffer. Analysis of 150 fmol showed a decrease in the relative abundance of higher molecular weight peptides. The incorporation of 5-methoxysalicylic acid (5MSA) as a comatrix in a molar ratio of analyte:fucose:DHB:5MSA = 1:5000:5000:50 gave signals for 45 out of 51 peptides for 4.5 pmol of a tryptic digest of rt-PA, corresponding to 88% of the expected fragments. Unobserved peptides were typically di- and tripeptides. Three glycopeptides were observed with peaks corresponding to the known major glycoforms. The fucose/DHB and 5MSA/DHB comatrices produced significant enhancements in spectral quality over DHB alone, including suppression of matrix peaks, increased ion signal, improved resolution, increased number of useful laser shots per crystal, and minimization of baseline slope. Spectra obtained with fucose/DHB generally surpassed DHB/5MSA in quality, though both matrix mixtures were clearly superior to neat DHB. Fucose/DHB demonstrated an increase in tolerance to ionic contaminants by producing a 10-fold reduction in the abundance of (M + Na)+ions. A trimatrix, DHB/5MSA/fucose, produced the highest quality spectra to date, although only marginally better than the fucose/DHB comatrix. PMID- 8368525 TI - Static secondary ion mass spectrometric investigation of the surface chemistry of organic plasma-deposited films created from oxygen-containing precursors. 3. Multivariate statistical modeling. AB - Partial least squares (PLS) multivariate statistical models were developed to predict the surface composition and chemistry of a set of model homopolymers based on their static SIMS fragmentation patterns. In the calibration or model building step, the positive and negative ion static SIMS spectra of different classes of model homopolymers were related to specific chemical attributes of the polymers. The models were then used to examine the surface chemistry of oxygen containing plasma-deposited films prepared from a variety of precursors. PLS models were developed to predict the surface oxygen concentration and H/C ratios. The results obtained from the PLS models were compared with experimental results. PMID- 8368526 TI - Remeasurement of ions using quadrupolar excitation Fourier transform ion cyclotron resonance spectrometry. AB - Ions formed by a single laser desorption event can be remeasured more than 500 times in a Fourier transform ion cyclotron resonance spectrometer. Quadrupolar excitation and collisional axialization are used to move ions located in any region of the ICR cell to the center of the cell, where they can be effectively detected. With this method, the signal from ions formed by a single laser desorption event is averaged for 200 remeasurement cycles with an efficiency in excess of 99.5% per cycle. Collisions of ions with helium are found to give higher remeasurement efficiencies than collisions with methane, due to reduced scattering losses by the lighter collision gas. With this method, ions that are stored in the analyzer cell for more than 1 hour can be detected. This technique is shown to be compatible with high-resolution data acquisition. Ions formed by one laser desorption event are remeasured at eight bandwidths, demonstrating low resolution, wide-mass-range analysis and high-resolution, narrow-mass-range analysis of the same group of ions. PMID- 8368527 TI - Enhanced mass resolving power, sensitivity, and selectivity in laser desorption Fourier transform ion cyclotron resonance mass spectrometry by ion axialization and cooling. AB - Ion cooling and axialization produced by azimuthal quadrupolar excitation in the presence of ion-neutral collisions are applied to laser desorption Fourier transform ion cyclotron resonance mass spectrometry (LD/FT/ICR-MS). With this technique, the large kinetic and internal energies of ions generated by laser desorption processes can be cooled effectively by collisions of ions with neutral argon atoms (at > 5 x 10(-7) Torr). After sufficient cooling in the source compartment of a dual ion trap, the axialized ions may be transferred to the analyzer compartment for detection at much lower pressure (and thus much higher mass resolving power). Enhancements in both FT/ICR mass resolving power and sensitivity are observed; moreover, ion isolation with high selectivity at high pressure is also demonstrated. PMID- 8368528 TI - Electrical field-flow fractionation in particle separation. 1. Monodisperse standards. AB - In its original implementation, electrical field-flow fractionation (EFFF) was carried out in membrane-walled channels with the electrodes placed externally to the flow channel. The poor separation efficiency of this system left the technique largely unattended for about two decades. In the present study, we describe a new and simple approach to EFFF, which demonstrates the technique's ability to carry out rapid, high-resolution separations of colloidal samples in aqueous suspensions. The present channels are bounded by the smooth and rigid graphite electrodes which allow for the application of small voltages, typically less than 2 V, across the thin (178 microns) separation space defined by a Mylar spacer. Although this arrangement generates nominal fields of the order of 100 V/cm, polarization of the electrodes considerably reduces the effective field across the bulk of the channel to less than 1% of the nominal value. Nevertheless, under conditions of low ionic strength the system is shown to retain and separate polystyrene (PS) latex standards with sizes ranging from 60 to 10,000 nm. For small particles of comparable zeta-potential, separating in the "normal" mode of EFFF, the size selectivity Sd, is approximately 0.7. As with other FFF techniques, EFFF displays a transition from "normal" to "steric" behavior; the critical diameter for this transition is highly dependent on ionic strength, with values ranging from approximately 500 nm in deionized water to approximately 1200 nm in 133 microM aqueous NaCl under an applied voltage of 1.37 V and a flow of 1 mL/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368529 TI - Automatic gas chromatographic determination of N-methylcarbamates in milk with electron capture detection. AB - A new analytical method that combines on-line derivatization-extraction and gas liquid chromatography for the determination of N-methylcarbamates is reported. The hydrolysis products of N-methylcarbamates (phenols) are derivatized and extracted in a continuous fashion using pentafluoropropionic anhydride (derivatizing reagent) in n-hexane as an extractant. The thermal instability of N methylcarbamates is overcome by forming fluoro derivatives that can be identified and quantified at the nanogram per milliliter level with an ECD detector. Application of the proposed method to six mixtures of N-methylcarbamates yielded detection limits between 2 and 20 ng/mL and a relative standard deviation of 2.35 3.70%. Average recoveries of N-methylcarbamates added to cow's milk at concentrations between 50 ng/mL and 2 micrograms/mL ranged from 93.7 to 100.8%. PMID- 8368530 TI - Enzyme immunoassay using a rat prolactin-alkaline phosphatase recombinant tracer. AB - This paper describes a competitive enzyme immunoassay of rat prolactin (rPrl) using a recombinant conjugate as a colorimetric tracer. rPrl was inserted into the N-terminal end of Escherichia coli alkaline phosphatase (AP), using an expression vector which allows insertion of foreign DNA sequences between codons +6 and +7 of the phoA gene. The assay was performed in 96-well microtiter plates coated with a mouse monoclonal antibody raised against rabbit immunoglobulin G. Each component (recombinant tracer, rabbit antiserum against rPrl, and rPrl standard) was added in a volume of 50 microL. The sensitivity of the assay was sufficiently high to allow titration of rPrl in plasma. The detection threshold was 15 pg (0.3 ng/mL) and the B/B0 50% value was 150 pg (3 ng/mL). The intraassay coefficient of variation was less than 10% over a wide range of rPrl concentrations (2.9-50 ng/mL). The interassay coefficient of variation was less than 15% for rat plasma samples in the concentration range of 4-40 ng/mL. The good parallelism observed between the standard curve and sample dilution curves showed that the immunoreactivity in rat plasma behaves like standard rPrl. Together with recovery experiments, these results indicated that assay without extraction is possible. A single immunoreactive peak that comigrates with standard rPrl is observed after molecular sieve fractionation of plasma samples. The reliability of the assay was confirmed by good correlation with conventional radioimmunoassay (r = 0.996, slope 0.978). PMID- 8368531 TI - Line scanning system for direct digital chemiluminescence imaging of DNA sequencing blots. AB - A cryogenically cooled charge-coupled device (CCD) camera equipped with an area CCD array is used in a line scanning system for low-light-level imaging of chemiluminescent DNA sequencing blots. Operating the CCD camera in time-delayed integration (TDI) mode results in continuous data acquisition independent of the length of the CCD array. Scanning is possible with a resolution of 1.4 line pairs/mm at the 50% level of the modulation transfer function. High-sensitivity, low-light-level scanning of chemiluminescent direct-transfer electrophoresis (DTE) DNA sequencing blots is shown. The detection of DNA fragments on the blot involves DNA-DNA hybridization with oligonucleotide-alkaline phosphatase conjugate and 1,2-dioxetane-based chemiluminescence. The width of the scan allows the recording of up to four sequencing reactions (16 lanes) on one scan. The scan speed of 52 cm/h used for the sequencing blots corresponds to a data acquisition rate of 384 pixels/s. The chemiluminescence detection limit on the scanned images is 3.9 x 10(-18) mol of plasmid DNA. A conditional median filter is described to remove spikes caused by cosmic ray events from the CCD images. PMID- 8368532 TI - Detection of nitric oxide production from a perfused organ by a luminol-H2O2 system. AB - Nitric oxide, thought to be the endothelium-derived relaxing factor (EDRF), is involved in intra- and intercellular signalling in various tissues. A system for the continuous detection of NO in the picomolar range from a perfused organ is described. The detection is based upon the chemiluminescence reaction between NO and the luminol (5-amino-2,3-dihydro-1,4-phthalazinedione)-H2O2 system. The chemiluminescence is due to the formation of peroxynitrite from NO and H2O2. The luminol-H2O2 system is specifically reactive to NO, so that other nitrogen containing compounds, (organic nitrite, organic nitrate, and thio-nitroso compounds) or endothelium-derived compounds do not interfere. The limit of determination was approximately 100 fM. This system has been used to measure continuous NO release from isolated perfused rat kidney and the simultaneous changes of perfusion pressure. In Wistar rats basal NO release was 85 +/- 11 fmol/min-1 (g of kidney weight)-1 (39 pM in the perfusate), and acetylcholine increased NO release dose dependently with a concomitant pressure reduction. The changes in NO release were always associated with mirror image changes in the perfusion pressure. Simple pressure reduction did not interfere with the chemiluminescence. Precise titration data as well as results of some preliminary experiments using this method are presented. PMID- 8368533 TI - Elemental speciation with plasma mass spectrometry. PMID- 8368534 TI - Improved data-processing method for atomic absorption spectroscopy with electrothermal atomization. AB - A new approach is described for processing transient data from electrothermal atomizers used in atomic absorption spectroscopy. The transient responses are first integrated and then a pseudo-first-order model is fit to the time-dependent integrals in order to predict the response that would be measured if the atomization process were monitored to completion. The principal advantage expected and observed for the new approach is its ability to reduce effects of variables such as atomization temperature. For all elements studied (Cr, Mn, K, Yb, Fe), the new predictive approach is shown to be virtually independent of temperature in the range from 2200 to 2600 degrees C. The predictive approach exhibited lower temperature coefficients than either the peak-height or peak-area options for all elements examined. For the more volatile elements (Mn, K, Yb, Fe), the improvement ratio at 2400 degrees C of the predictive approach relative to the others ranged from 1.4 to 8.2. For chromium at 2400 degrees C, the temperature coefficient of the predictive method was approximately 10- and 30 fold lower than those for the peak-area and peak-height options, respectively. PMID- 8368535 TI - Peptide mapping and evaluation of glycopeptide microheterogeneity derived from endoproteinase digestion of erythropoietin by affinity high-performance capillary electrophoresis. AB - High-performance capillary electrophoresis (HPCE) has been employed to characterize the peptide map of recombinant human erythropoietin (rHuEPO) expressed from Chinese hamster ovary (CHO) cells. The methodology employs an ion pairing agent, 100 mM heptanesulfonic acid in 40 mM sodium phosphate buffer, pH 2.5, to increase peptide resolution, to decrease analyte wall interactions, and to evaluate glycopeptide microheterogeneity. The total tryptic map is segregated into two regions, nonglycosylated and glycosylated peptides. Reproducibility of the peptide map is excellent; the map results in baseline separation of 16 tryptic peptides and one doublet peak composed of two peptides (resolution 0.22). The map furthermore allows for the evaluation of the microheterogeneity associated with the three rHuEPO glycopeptides. At least 12 glycopeptide forms were separated in the initial peptide map. Peptides were identified by Edman sequencing, and the glycopeptides were further subjected to Dionex anion-exchange chromatography. To simplify the level of complexity associated with the glycopeptides, much of the characterization employed asialoglycopeptides and employed several endoproteolytic diagnosis. The relative percent distribution for each purified asialoglycopeptide was calculated to define the level of complexity and to tentatively assign a known structure to the HPCE peak. The level of structural complexity of the asialoglycopeptides appears to increase from the simplest O-linked form to the more complex N83, N38, and N24 glycosylation positions, respectively. HPCE evaluation of glycopeptide microheterogeneity appears to be simpler, faster, and just as sensitive as other more frequently employed methods for glycopeptide characterizations. PMID- 8368536 TI - Amperometric monitoring of chemical secretions from individual pancreatic beta cells. AB - The goal of the work was to develop and test an amperometric method for measuring insulin secretion from individual pancreatic beta-cells. The electrode used was a carbon fiber microelectrode modified with a polynuclear ruthenium oxide/cyanoruthenate film. The chemically modified electrode allowed anodic detection of insulin in physiological buffers with a detection limit of 0.5 microM. To measure secretion, an electrode was positioned 1 micron away from a beta-cell that had been stimulated with K+ or glucose. Recordings made from the cells consisted of a series of current spikes averaging 38 ms full width at half height. The spikes decreased in height and increased in width as the electrode was pulled away from the cell. Spikes were only observed if a modified electrode was used and its potential was sufficient to oxidize insulin. The area under the spikes correspond to approximately 600 zmol of insulin, which is within the expected range for vesicular insulin content. Spike area was independent of stimulation method. The results support the hypothesis that the electrode was anodically detecting a substance secreted from the cells by exocytosis. The results support, but do not prove, that insulin was the primary substance detected. PMID- 8368537 TI - Kinetic study of the reaction of acetoacetate with glycine and sodium nitroprusside. AB - This paper describes an extensive kinetic study of the reactions involved in the determination of acetoacetate in body fluids. It is concluded that acetoacetate reacts with glycine to produce an imine intermediate that tautomerizes to an enamine. It is also concluded that nitroprusside reacts with the imine intermediate to produce an unstable product with an absorption maximum near 540 nm. This product decays slowly to produce a stable product with an absorption maximum near 393 nm. A proposed reaction pathway is used to develop kinetic equations, rate constants, equilibrium constants, and molar absorptivity of the unstable product that permit quantitative prediction of the kinetic behavior for a wide range of reactant concentrations. PMID- 8368538 TI - Ion beams and laser postionization for molecule-specific imaging. PMID- 8368539 TI - Anesthesiology and critical care medicine. PMID- 8368540 TI - Attitudes of anesthesiology residents toward critical care medicine training. AB - The number of anesthesiology residents pursuing critical care medicine (CCM) fellowship training has been decreasing in recent years. A significant number of training positions remain unfilled each year. Possible causes of this decline were evaluated by surveying residents regarding their attitudes toward practice and training in CCM. All 38 anesthesiology programs having accredited CCM fellowships were surveyed. Four of these and one program without CCM fellowships were used to develop the survey instrument. Four programs without CCM fellowships and 34 programs with CCM fellowships make up the survey group. Returned were 640 surveys from 37 (97%) programs accounting for over 30% of the possible residents. Resident interest in pursuing CCM training decreased as year of residency increased (P < 0.0001). Residents in programs with little patient care responsibility during intensive care unit (ICU) rotations expressed less interest in CCM training (P < 0.012). The administrative role of the anesthesiology department in the ICU also influenced resident interest (P < 0.014). Written responses to open-ended questions suggested resident concerns with the following: stress of chronic care, financial consequences of additional year of training, ICU call frequency and load, ICU role ambiguity, and shared decision-making in the ICU. A recurring question was, "Are there jobs (outside of academics) for anesthesiologist intensivists?" Most residents knew a CCM anesthesiologist they admired and knew that there were unfilled fellowship positions available. Defining the job market, improving curriculum and teaching, supporting deferment of student loans, and introducing residents and medical students to the ICU earlier may increase the interest in CCM practice among anesthesiology residents. PMID- 8368541 TI - Effect of vasopressin on hemodynamic variables, organ blood flow, and acid-base status in a pig model of cardiopulmonary resuscitation. AB - Based upon the hypothesis that vasopressin (antidiuretic hormone) may increase vascular resistance during ventricular fibrillation, the effects of this potent vasoconstrictor were studied in a porcine model of ventricular fibrillation. Vasopressin therapy was compared to epinephrine by randomly allocating 14 pigs to receive either 0.045 mg/kg of epinephrine (n = 7) or 0.8 U/kg of vasopressin (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest cardiopulmonary resuscitation. During cardiopulmonary resuscitation, myocardial blood flow before and 90 s and 5 min after drug administration was 57 +/- 11, 84 +/- 11, and 59 +/- 9 mL.min-1 x 100 g-1 (mean +/- SEM) in the epinephrine group, and 61 +/- 5, 148 +/- 26, and 122 +/- 22 mL.min-1 x 100 g-1 in the vasopressin group (P < 0.05 at 90 s and 5 min). At the same times, mean cardiac index was not significantly different between the groups. After drug administration, coronary venous PCO2 was significantly higher and coronary venous pH was significantly lower in the epinephrine as compared to the vasopressin group. All pigs in both groups were resuscitated and survived the 2-h observation period. We conclude that vasopressin improves vital organ perfusion during ventricular fibrillation and cardiopulmonary resuscitation. Vasopressin seems to be at least as effective as epinephrine in this pig model of ventricular fibrillation. PMID- 8368542 TI - Selecting ventilator settings according to variables derived from the quasi static pressure/volume relationship in patients with acute lung injury. AB - Knowledge of the pressure/volume (P/V) relationship of the lung may allow selection of tidal volume and positive end-expiratory pressure (PEEP) to optimize gas exchange without adversely affecting lung function or hemodynamics. Ten patients with acute lung injury were stabilized on controlled mechanical ventilation, based on conventional practice, using criteria from arterial blood gas data. The P/V relationship was determined under quasi-static conditions (end expiratory and end-inspiratory, no flow periods > 0.8 s) during mechanical ventilation with an automated procedure that changed PEEP in a stepwise fashion. Differences in expiratory tidal volumes before and after a change in PEEP equaled the change in functional residual capacity (delta FRC). PEEP was set above the lowest point of the steepest section of the P/V curve (inflection pressure) to prevent end-expiratory lung collapse. Inspiratory tidal volumes (VTI) were adjusted to avoid an end-inspiratory lung volume reaching the flat part of the P/V curve. Averaged delta FRC versus PEEP curves were shifted to the left and the slope increased 1, 6, and 12 h after changing ventilator settings compared to baseline (P < 0.01). Averaged baseline delta FRC versus PEEP curves showed a marked inflection pressure that decreased after adjusting ventilator settings (P < 0.01). PEEP was increased from 7.4 +/- 1.8 cm H2O (baseline) to 11.9 +/- 1.6 cm H2O (1 h) (P < 0.001) according to measured baseline inflection pressures. Simultaneously, VTI had to be reduced from 759 +/- 161 mL (baseline) to 664 +/- 101 mL (1 h) (P < 0.01) to avoid end-inspiratory overinflation. To maintain minute volume constant ventilator frequency was increased from 14 +/- 1.2 (baseline) to 16 +/- 1.2 breaths/min (1 h) (P < 0.01). Maximum quasi-static compliance of 38 +/- 7 mL/cm H2O (baseline) increased to 46 +/- 9 mL/cm H2O (1 h) (P < 0.01). Maintaining FIO2 constant, PaO2 increased from a baseline of 90 +/- 16 mm Hg to 122 +/- 24 mm Hg (1 h) (P < 0.001), to 130 +/- 20 mm Hg (6 h) (P < 0.01), and to 138 +/- 19 mm Hg (12 h) (P < 0.01). Intrapulmonary shunt decreased from 0.28 +/- 0.08 (baseline) to 0.14 +/- 0.05 (12 h) (P < 0.001). Hemodynamic variables did not change. Our data suggest that using variables derived from a quasi-static P/V loop during mechanical ventilation under muscle paralysis is clinically superior compared to blood gas criteria for titration of ventilator settings. PMID- 8368543 TI - Venous air embolism during cesarean section: more common than previously thought. AB - To confirm the incidence of venous air embolism (VAE), we simultaneously monitored expired nitrogen concentration (FEN2) and precordial Doppler in 30 patients undergoing cesarean delivery during general anesthesia. Patients were randomized into two groups and the effect of a 10 degrees reverse Trendelenburg tilt versus the horizontal position was evaluated. Forty-two episodes of VAE, defined by an increase in FEN2 of 0.1%, were detected in 97% (29/30) of patients. Doppler ultrasound failed to detect 9 of the episodes and 23 (41%) changes in Doppler tones were not associated with an increase in FEN2. These spurious Doppler signals were synchronous with compression of retroperitoneal structures, suggesting turbulent venous return to be the cause. The reverse Trendelenburg position did not reduce the incidence of VAE. Compared with the preinduction baseline, mean arterial blood pressure decreased by 31.5 +/- 10.1 mm Hg in this position and 22.6 +/- 13.4 mm Hg in the supine position after hysterotomy. We conclude that VAE in cesarean delivery during general anesthesia occurs very frequently, and that changes in Doppler tones may not be reliable indicators of this complication. Measures to reduce the size and effect of air emboli therefore should be applied routinely in all patients. PMID- 8368544 TI - Anesthesia for in vitro fertilization: a comparison of 1.5% and 5% spinal lidocaine for ultrasonically guided oocyte retrieval. AB - In many institutions, spinal anesthesia is used for surgery involving ultrasonically guided transvaginal oocyte retrieval. Because this relatively short procedure is performed on an outpatient basis, the optimal spinal technique would allow good surgical anesthesia with a short recovery time. The relative regression of equal doses of different concentrations of hyperbaric spinal lidocaine is presented. We compared 1.5% and 5% hyperbaric lidocaine (7.5% dextrose) as spinal drugs for use in this procedure. Fifty-six patients were randomized to receive 60 mg of hyperbaric solutions of either 1.5% or 5% lidocaine in combination with 10 micrograms of spinally administered fentanyl. Visual analog scale pain scores were zero throughout the procedures for all patients. There were no significant differences between the groups with regard to sensory level, maximum motor block, intravenous sedation requirements, time to two-segment regression, and time to full sensory recovery. The group receiving 1.5% lidocaine had significantly shorter times to ambulation (141 +/- 21 min vs 162 +/- 29 min; P < 0.05), voiding (147 +/- 21 min vs 174 +/- 28 min; P < 0.05), full motor recovery (86 +/- 21 min vs 111 +/- 22 min; P < 0.0001), and discharge (170 +/- 38 min vs 201 +/- 41 min; P < 0.05). The use of 1.5% hyperbaric lidocaine for transvaginal oocyte retrieval provides a significantly shorter recovery time when compared to 5% hyperbaric lidocaine and is a good choice for spinal anesthesia for this procedure. PMID- 8368545 TI - A clinical and laboratory study to compare the addition of 0.2 mg of morphine, 0.2 mg of epinephrine, or their combination to hyperbaric bupivacaine for spinal anesthesia in cesarean section. AB - The aim of this prospective, randomized, double-blind study was to compare the effects of adding either preservative-free morphine, 0.2 mg (n = 20), epinephrine, 0.2 mg (n = 21), or a combination of both (n = 29) to hyperbaric bupivacaine in parturients having elective cesarean sections during spinal anesthesia. Ten additional patients receiving spinal bupivacaine alone were studied as the Control Group. High-pressure liquid chromatography with a sensitivity of 20 micrograms/mL was used to measure serum bupivacaine in all subjects. The results showed that the spread and regression of the sensory and motor blocks were similar among the study groups. However, the intraoperative analgesia was superior in patients receiving bupivacaine combined with morphine and epinephrine, whereas there was no difference between those given an addition of either morphine or epinephrine. Postoperative analgesia was the shortest and opioid requirement in the first 24 h the most with epinephrine alone. No respiratory depression occurred. The neonatal condition was excellent in all groups. Serum concentrations of bupivacaine at 10 min, at delivery (25 +/- 1.4 min), and at 60 min after the intrathecal injection were similar among the groups including the Control Group. The concentrations of bupivacaine in umbilical arterial and venous sera were less than the sensitivity level of the analytical method. We conclude that the addition of 0.2 mg of morphine plus 0.2 mg of epinephrine to hyperbaric bupivacaine improves the intra- and postoperative analgesia without an added risk. This improvement is not due to vasoconstriction and a reduction in the absorption of bupivacaine from the subarachnoid space. PMID- 8368546 TI - Myocardial uptake of bupivacaine: I. Pharmacokinetics and pharmacodynamics of lidocaine and bupivacaine in the isolated perfused rabbit heart. AB - Bupivacaine, but not lidocaine, may cause severe cardiac dysrrhythmias in case of accidental intravascular injection. In an attempt to discriminate between a pharmacokinetic and a pharmacodynamic (or both) origin to these differences, we used an isolated rabbit heart model with constant coronary inflow to compare the myocardial uptake and disposition kinetics of lidocaine and bupivacaine. Drug concentration in the outflow perfusate was assayed and surface electrocardiogram was recorded. Drug uptake and disposition kinetics were modeled with a two compartment open model. An Emax model was used to describe the increase in QRS duration in relation with drug concentration in the central compartment. Lidocaine and bupivacaine exhibited similar myocardial pharmacokinetics (i.e., a rapid decrease in the outflow concentration upon drug administration discontinuation). Bupivacaine-induced maximum increase in QRS duration (Emax) was 15 times superior to lidocaine Emax. The steady-state perfusate concentration producing half Emax was the same for both drugs. We conclude that bupivacaine induced QRS widening decreases almost at the same rate as does lidocaine-induced QRS widening when drug administration is terminated. Therefore, the different cardiac effects of lidocaine and bupivacaine are not due to differences in myocardial uptake and disposition kinetics. PMID- 8368547 TI - Myocardial uptake of bupivacaine: II. Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart. AB - The enantiomers of a racemic drug generally differ in their pharmacokinetic and/or pharmacodynamic properties. Because bupivacaine is a mixture of two optical isomers known to exert different toxic properties on isolated nerve preparations, we decided to use an isolated rabbit heart model with constant coronary inflow to compare the myocardial uptake kinetics of the R(+)-, S(-) enantiomers and the racemic mixture of bupivacaine. The increase in QRS duration was also measured, and the inflow concentration-effect relationship was analyzed for the three drugs. The racemic and the two enantiomers of bupivacaine exhibited similar myocardial pharmacokinetics with a two-compartment profile for all hearts except one. All drugs showed a rapid decrease in the outflow concentration when drug administration was discontinued. The tissue/perfusate concentration ratio at steady state was similar for the three drugs. QRS widening, as well as the occurrence of severe arrhythmias, was much less pronounced in the hearts receiving the S(-) isomer than in the hearts receiving the R(+) isomer or the racemic mixture. Despite the occurrence of arrhythmias, QRS widening was adequately modelled with an Emax model. C50, the inflow perfusate concentration producing half Emax (maximal theoretical increase in QRS duration) was the same for all three drugs. The authors conclude that the S(-)-bupivacaine exerts less detrimental effects on the isolated heart of the rabbit perfused at a constant coronary flow with protein-free buffer. PMID- 8368548 TI - Influence of injection speed on the subarachnoid distribution of isobaric bupivacaine 0.5%. AB - The purpose of this study was to compare the anesthetic characteristics after two radically different speeds of intrathecal injection of isobaric 0.5% bupivacaine during continuous spinal anesthesia. Forty consenting patients, undergoing hip surgery using continuous spinal anesthesia, were allocated randomly to two groups of 20 each according to the rate of injection of 2 mL (10 mg) of isobaric 0.5% bupivacaine: FI (fast injection = 2 mL during 2 to 3 s or approximately 0.75 mL/s) or SI (slow injection = 1 mL/min). No difference was observed between the two groups in terms of sensory and motor block or hemodynamic changes. However, the onset time to maximal sensory level was significantly shorter in the SI group (16 +/- 9 min vs. 24 +/- 6 min; P < 0.05). Those patients requiring reinjection entered the second part of the study (n = 23; 15 in the FI group and 8 in the SI group). Each of these remaining patients was used as his or her own proper control. Those in the FI group received a slow reinjection and those in the SI group received a fast reinjection which consisted in all cases of 10 mg (2 mL) of isobaric 0.5% bupivacaine. When looking at the anesthetic characteristics after reinjection, maximal sensory levels, as well as onset times, were very similar in both groups. At all times, the maximal sensory level obtained after reinjection was two dermatomes higher than after the initial injection. Duration of sensory block, which was calculated only in these 23 patients, was also comparable (126 +/- 44 min for FI and slow reinjection group vs 146 +/- 25 min for SI and fast reinjection group). In conclusion, regardless of the speed of injection, there are no differences in anesthetic characteristics of spinal anesthesia using isobaric 0.5% bupivacaine. PMID- 8368549 TI - Preanesthetic skin-surface warming reduces redistribution hypothermia caused by epidural block. AB - Redistribution of heat from the core to the cool peripheral compartments of the body causes hypothermia during epidural anesthesia. Diminishing the temperature gradient between the core and peripheral tissues by warming the body via the skin before anesthesia should prevent this hypothermia. We measured core temperature, skin temperatures, and cutaneous heat loss in seven volunteers who received two lidocaine epidural injections during a single study day. One epidural injection was given after the volunteer had rested in a cool room (approximately 22 degrees C) ("no prewarming") for 2 h, and one injection was given after the volunteer had been covered with a forced air warming mattress (approximately 38 degrees C) ("prewarming") for 2 h. Skin temperatures were higher after prewarming. The decrease in core temperature during epidural anesthesia was smaller after prewarming [mean within patient difference (prewarming-no prewarming): 0.41; P = 0.003]. However, heat loss was greater after prewarming (mean within patient difference: 26.4; P = 0.02). Shivering was less after prewarming. We conclude that prewarming decreases redistribution hypothermia caused by epidural block. These results support the hypothesis that redistribution of heat within the body, not heat loss, is the most important etiology of hypothermia from epidural anesthesia. PMID- 8368550 TI - Thoracic epidural anesthesia causes rib cage distortion in anesthetized, spontaneously breathing dogs. AB - The effects of thoracic epidural anesthesia on the performance of the parasternal intercostal muscles were investigated by measuring electromyographic activity and length changes of the parasternals (EMG activities and length, respectively, of the parasternals) in seven pentobarbital anesthetized, spontaneously breathing dogs. Epidural injection of 0.1 mL/kg of 2% lidocaine decreased tidal volume and minute ventilation during unstimulated breathing. These changes were accompanied by complete abolishment of EMG activities of the parasternals and passive elongation of the parasternals during inspiration. At equivalent end-tidal PCO2 values (70 and 80 mm Hg) during CO2 rebreathing, tidal volume and minute ventilation were lower after epidural block compared to the corresponding values before the block. Thoracic epidural anesthesia impaired contraction of the parasternals and conceivably other respiratory muscles in the rib cage as well and could induce a distortion of the rib cage. The authors conclude that respiratory muscles in the rib cage contribute considerably to the maintenance of ventilation in anesthetized dogs. PMID- 8368551 TI - Effects of halothane and isoflurane on collateral dependent myocardium in chronically instrumented dogs. AB - The effects of moderate systemic hypotension with halothane (HALO) and isoflurane (ISO) on regional myocardial function and perfusion were studied in dogs with chronic coronary artery occlusion. Vasodilator reserve in collateral-dependent (CD) myocardium was quantified in conscious animals by using a dipyridamole challenge test. Blood flow was distributed homogeneously to the normal (Nl) and CD myocardium at rest, but subendocardial perfusion increased only in the Nl area after dipyridamole. HALO and ISO were administered at doses that reduced diastolic arterial pressure to 50 mm Hg. End-tidal concentrations were 1.3 +/- 0.2 vol% for HALO (1.5 minimum alveolar anesthetic concentration) and 1.8 +/- 0.2 vol% for ISO (1.4 minimum alveolar anesthetic concentration), respectively. Global and regional hemodynamic depression were more pronounced with HALO. Systolic wall-thickening fraction decreased both in the Nl (-37%) and CD area ( 27%). Myocardial blood flow to Nl and CD myocardium decreased to a comparable extent. ISO predominantly decreased systemic vascular resistance and, when compared to HALO, decreased systolic wall-thickening fraction less in both the Nl (-19%) and CD area (-18%). In addition, regional myocardial perfusion to both Nl and CD myocardium remained virtually unaltered from conscious control conditions. Despite reductions of diastolic blood pressure to 50 mm Hg, neither HALO nor ISO induced ischemic dysfunction in myocardium with diminished vasodilator reserve. Both anesthetics preserved intercoronary as well as transmural blood flow distribution. During HALO, myocardial perfusion was less both in Nl and CD myocardium due to a more pronounced metabolic depression. We conclude that moderate hypotensive doses of ISO and HALO preserve regional myocardial function of collateral-dependent myocardium in dogs with single vessel occlusion and enhanced collateral circulation. PMID- 8368552 TI - Serial intravenous doses of dezocine, morphine, and nalbuphine in the management of postoperative pain for outpatients. AB - Adult patients who had arthroscopic surgery under general anesthesia and requested postoperative pain relief were randomized to receive treatment in a double-blind protocol with 5 mg of intravenous dezocine (20 patients), morphine (22 patients), nalbuphine (18 patients), or saline (24 patients). At 10-min intervals, starting with the first dose of analgesic, patients could choose up to three additional doses of the primary treatment, or choose an alternative analgesic if the primary drug was unsatisfactory. One to four doses of morphine were given as the alternate treatment if the initial treatment was dezocine or nalbuphine, and one to four doses of dezocine were given if the initial treatment was saline or morphine. The proportion of patients treated successfully by the initial treatments (i.e., not requesting alternate treatment), with P value for difference from placebo treatment, were saline 25%, nalbuphine 33% (P = 0.048), morphine 54% (P = 0.04), and dezocine 75% (P = 0.003). Dezocine and morphine are more efficacious than nalbuphine in the management of early postoperative pain. As an alternate analgesic in this study, dezocine required fewer doses to achieve patient satisfaction and was thus more efficacious than morphine. The incidence of treatment-related, adverse effects was different from that of saline or other treatments only for nalbuphine-related pain or burning on injection and dezocine related facial itching. With respect to analgesic actions and side effects, dezocine seems more like morphine than nalbuphine. PMID- 8368553 TI - Inhaled induction and emergence from desflurane anesthesia in the ambulatory surgical patient: the effect of premedication. AB - We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia. PMID- 8368554 TI - Propofol at a subanesthetic dose may have abuse potential in healthy volunteers. AB - We conducted a study in which the rewarding effects of propofol were assessed in humans, using a discrete-trials choice procedure. Normal healthy volunteers (n = 12) were exposed in a blind fashion to acute bolus injections of 0.6 mg/kg of propofol twice and to a similar volume of Intralipid twice. Then, for the next three sessions, subjects chose which drug (identified by a color code) they wished to receive. We defined propofol choosers if individuals chose propofol two or three times, and nonchoosers if they chose propofol once or not at all. By using a chi 2 goodness-of-fit test of a random choice model, the choice distribution differed significantly from a random choice distribution (P < 0.005). Six subjects were choosers: four subjects chose propofol on all three choice occasions and two subjects chose the drug on 2/3 occasions (referred to hereafter as propofol choosers). Six subjects were nonchoosers: five subjects chose Intralipid on all three choice occasions, and one subject chose Intralipid twice (referred to hereafter as propofol nonchoosers). During sampling sessions, propofol choosers reported pleasant acute effects and no unpleasant residual effects, whereas propofol nonchoosers reported either unpleasant acute subjective effects and/or residual effects from propofol. We conclude that 1) propofol may be rewarding (reinforcing) in some individuals without a history of drug abuse, and 2) further abuse liability testing is needed with this drug. PMID- 8368555 TI - Chronic alcoholism increases the induction dose of propofol in humans. AB - The doses of propofol that produce loss of consciousness were investigated in 26 patients with chronic alcoholism and in 20 patients with a history of small alcoholic intake undergoing ear, nose, and throat surgery under general anesthesia. Last ethanol consumption by the alcoholics was 24 h preoperatively, as they had no access to alcohol when admitted to the hospital. Propofol was infused at a rate of 1200 mL/h (200 mg/min). The doses required to produce (a) loss of verbal contact and (b) loss of ability to grasp a 20-mL syringe filled with water were recorded. At this time a 2-mL venous blood sample was collected to detect propofol blood concentrations. A painful stimulus was applied to the abdomen, and a positive or negative response was noted. The mean +/- SD dose of propofol required for loss of verbal contact was 2.7 +/- 0.42 mg/kg in the alcoholic group and 2.2 +/- 0.43 mg/kg in the control group (P < 0.001). The dose of propofol required for dropping the syringe was significantly higher in the alcoholic group, 4.2 +/- 1.02 mg/kg versus 3.2 +/- 0.75 mg/kg in the control group (P < 0.01). The two groups did not differ significantly regarding the propofol blood concentrations at loss of consciousness, or the frequency of response or no response to painful stimulus. These findings suggest that the doses of propofol required to induce anesthesia in chronic alcoholic patients are more than in patients who drink socially. PMID- 8368556 TI - Inotropic and electrophysiologic effects of propofol and thiamylal in isolated papillary muscles of the guinea pig and the rat. AB - We compared the inotropic and electrophysiologic effects of propofol and thiamylal in isolated papillary muscles of the guinea pig and rat. Propofol applied in clinical 10% intralipid emulsion showed concentration-dependent negative inotropic effects, accompanied by decreased action potential duration, in the guinea pig. Intralipid alone had no effect. Although thiamylal showed a concentration-dependent depression similar to propofol in the guinea pig, depolarization of resting membrane potential was seen at 0.1 and 0.3 mM, and a slight prolongation of action potential duration at 90% repolarization at 0.1 mM, and then a decrease of action potential duration at 0.3 mM. In rat papillary muscles, propofol did not produce any depression of contractile force, whereas thiamylal produced a concentration-dependent negative inotropic effect. The important findings observed in the action potential in rat papillary muscles were the modest shortening of action potential duration after propofol application, and the significant decrease of resting membrane potential and the significant prolongation of action potential duration caused by thiamylal. Both propofol and thiamylal depressed slow action potentials and contractile force in guinea pig papillary muscles depolarized by 25 mM K+ solution. In conclusion, the negative inotropic effects of propofol and thiamylal might be caused by inhibition of trans-sarcolemmal Ca2+ influx accompanied by shortening of action potential duration in guinea pig papillary muscles. The action potential of thiamylal might be affected by the suppression of K+ current in guinea pig and rat papillary muscles that was never observed in the propofol-treated tissue. PMID- 8368557 TI - Trabecular outflow facility and formation rate of aqueous humor during propofol, nitrous oxide, and halothane anesthesia in rabbits. AB - Propofol decreases intraocular pressure (IOP) and the IOP response to laryngoscopy and intubation, but the mechanisms responsible for this effect have not been reported. The present study examined the effect of propofol on IOP, intraocular fluid formation and outflow facility, and intraocular compliance. Twenty-two white New Zealand rabbits were anesthetized with halothane (0.8%-1.0% inspired concentration) in nitrous oxide (2 L/min) and oxygen (1 L/min). Muscle paralysis was established with pancuronium, and the lungs were mechanically ventilated through a tracheal tube. Twelve rabbits examined under these conditions served as controls. In the treatment group (n = 10), 6 mg/kg propofol followed by 18 mg.kg-1 x h-1 propofol intravenously was added to halothane/nitrous oxide/oxygen anesthesia. In both groups, a series of intraocular infusions was made via a 30-gauge needle in the anterior chamber, and IOP, the rate of aqueous humor formation (Fa), and trabecular outflow facility (Ctr) were determined using conventional analysis. These same measures, as well as intraocular compliance, were determined using a new method of analysis adapted from the manometric technique for determining cerebrospinal fluid dynamics. IOP was 11.3 +/- 1.8 mm Hg (mean +/- SD) in halothane-anesthetized controls and decreased to 9.4 +/- 2.2 mm Hg when propofol was added to halothane anesthesia (P < 0.05). By conventional analysis, Fa was 2.82 +/- 0.94 microL/min and Ctr was 0.121 +/- 0.044 microL.min-1 x mm Hg-1 in controls. After addition of propofol, Fa decreased by 24% to 2.15 +/- 0.62 microL/min (P < 0.05) and Ctr decreased by 18% to 0.099 +/- 0.034 microL.min-1 x mm Hg-1 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368558 TI - Muscle paralysis by rocuronium during halothane, enflurane, isoflurane, and total intravenous anesthesia. AB - We determined the dose-response relationship, the onset time, the duration, and the recovery time of a rocuronium neuromuscular block under four anesthesia techniques. Patients were equally randomized to four different groups (n = 20) receiving 0.5%-1% halothane, 1.5%-2% enflurane, 1.2%-1.8% isoflurane end-tidal concentration in 34%/66% O2/N2O, or 6.0 mg.kg-1 x h-1 propofol without N2O for anesthesia and alfentanil for analgesia. Strength of thumb adduction in response to single and train-of-four stimulation of the ulnar nerve was quantitated. Rocuronium 0.15, 0.2, 0.25, and 0.3 mg/kg were given intravenously. When maximal depression of twitch tension occurred, supplemental doses up to a total of 0.5 mg/kg were given. If required, additional doses of 0.15 mg/kg were given at 25% recovery of control twitch tension. Standard hemodynamics, end-tidal CO2, and anesthetic gas concentrations were monitored continuously. The mean ED50 (SD) was 0.133 (+/- 0.009) mg/kg for the halothane group, 0.118 (+/- 0.012) mg/kg for the enflurane group, 0.069 (+/- 0.026) mg/kg for the isoflurane group, and 0.167 (+/- 0.007) mg/kg for the total intravenous anesthesia (TIVA) group, respectively. There was a statistically significant difference between the halothane and TIVA, and between the enflurane and TIVA groups (P < 0.05). Rocuronium has a short onset time and an intermediate duration of action. The neuromuscular blocking potency and pharmacodynamic profile are moderately influenced by volatile anesthetics. PMID- 8368559 TI - Succinylcholine causes profound hyperkalemia in hemorrhagic, acidotic rabbits. AB - Two recent clinical reports suggested that succinylcholine (SCh) may cause severe hyperkalemia in hemorrhagic, acidotic humans. To investigate this, we anesthetized rabbits with halothane and N2O, and inserted venous and arterial catheters. Control rabbits (Group C, n = 4) remained anesthetized and undisturbed. Hemorrhage/profound acidosis (HPA) was accomplished by withdrawal of 25-30 mL/kg of blood and waiting until pHa approximately 7.05 (Group HPA, n = 5). Hemorrhage/minimal acidosis (HMA) was accomplished by withdrawal of 25-30 mL/kg of blood, but acidosis was minimized by not waiting for it to occur and by administering NaHCO3 0-1.4 mEq/kg (Group HMA, n = 4). In a metabolic acidosis group (n = 4), HCl was infused until pHa approximately 7.05. Respiratory acidosis (n = 4) was accomplished by partial obstruction of the endotracheal tube until PaCO2 approximately 120 mm Hg and pHa approximately 7.05. Potassium levels were determined before the above interventions (baseline), immediately before (pre SCh), and 1, 3, 5, 7, 10, and 13 min after SCh 1 mg/kg intravenously. In Group C, potassium gradually increased from 3.5 +/- 0.2 mEq/L to 4.8 +/- 0.2 mEq/L 13 min after SCh. In Group HPA, potassium increased from 3.8 +/- 0.3 to 7.0 +/- 1.8 mEq/L after hemorrhage/acidosis and then to 11.4 +/- 1.7 mEq/L at 13 min after SCh. The metabolic acidosis group was significantly different from Group C at 7, 10, and 13 min after SCh (maximum at 13 min, 6.8 +/- 1.2 mEq/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368560 TI - Evaluation of foil coverings for protecting plastic endotracheal tubes from the potassium-titanyl-phosphate laser. AB - The potassium-titanyl-phosphate laser is being used for airway surgery and could cause an endotracheal tube fire. To determine whether five different metallic foil tapes or the Laser-Guard protective wrap would protect polyvinylchloride (PVC) endotracheal tubes from this laser, it was set to a power of 18 W and aimed at the wrapped endotracheal tube under study for up to 1 min while 5 L/min of oxygen flowed through the endotracheal tube. A plain (unwrapped) PVC endotracheal tube was studied also. The plain PVC endotracheal tube was ignited by the laser after 14 s. Potassium-titanyl-phosphate laser radiation did not significantly affect the nonadhesive sides of the foil tapes tested or the Laser-Guard covering. However, potassium-titanyl-phosphate laser radiation caused ignition or melting of underlying PVC endotracheal tubes when it was applied to the endotracheal tubes with the adhesive side of the foil tapes facing outward. It is concluded that only the Laser-Guard protective coating adequately protected the PVC endotracheal tubes tested under the conditions of this experiment. PMID- 8368561 TI - Effects of midazolam on respiratory muscles in humans. AB - Midazolam at sedative doses alters the breathing pattern; however, its effects on respiratory load and respiratory muscle activity have not been established completely. Therefore, the effects of midazolam (0.1 mg/kg) on total pulmonary resistances and on diaphragmatic, intercostal, and abdominal muscle patterns were studied in nine volunteers. Measurements were performed during control, 5 and 10 min after midazolam, and then 2 min after 1.0 mg of intravenous flumazenil. After midazolam, total pulmonary resistance increased from 6.3 +/- 0.65 to 36.6 +/- 8.1 cm H2O-L-1 x s-1 (P < 0.01), a pattern associated with an increased intercostal electromyographic activity (peak and slope; P < 0.05). By contrast, the ratio of gastric pressure on esophageal pressure changes decreased from 65.5% +/- 6.2% to 16.3% +/- 3.9% (P < 0.01), indicating reduced diaphragmatic activity. In 7/9 subjects, there was expiratory abdominal muscle activity. Flumazenil reversed all these effects. We conclude that midazolam 0.1 mg/kg increases total pulmonary resistance and elicits a compensatory load response characterized by an increase in inspiratory intercostal and expiratory abdominal muscle activities whereas diaphragmatic contribution is reduced. PMID- 8368562 TI - Hepatic blood flow and energy metabolism during hypotension induced by prostaglandin E1 and nicardipine in rabbits: an in vivo magnetic resonance spectroscopic study. AB - Hepatic blood flow (HBF) and energy metabolism during moderate hypotension induced by prostaglandin E1 (PGE1) and nicardipine were studied by in vivo magnetic resonance spectroscopy. HBF was determined by the deuterated water clearance method by using deuterium magnetic resonance spectroscopy, and energy metabolism was estimated from the changes in the levels of adenosine triphosphate and inorganic phosphate by using phosphorus (31P) magnetic resonance spectroscopy. Mean arterial blood pressure was intentionally reduced to 60% of control with PGE1 (n = 5) or nicardipine (n = 5). The HBF decreased by 38% and by 50% during the hypotension induced by PGE1 and nicardipine, respectively. The level of adenosine triphosphate decreased by 12% and that of inorganic phosphate increased by 80% during nicardipine-induced hypotension, whereas the corresponding levels showed no remarkable changes during PGE1-induced hypotension. After the cessation of drug administration, mean arterial blood pressure and HBF recovered to the control levels in the PGE1 group, but not completely in the nicardipine group. In the latter group, the level of inorganic phosphate did not recover either. These results indicate that during hypotension induced with PGE1 hepatic circulation and metabolism are conserved to a greater extent than during hypotension induced with nicardipine. PMID- 8368563 TI - Endotoxin in septic shock. PMID- 8368564 TI - Management of the parturient with a history of local anesthetic allergy. PMID- 8368565 TI - Is spinal anesthesia after failed epidural anesthesia contraindicated for cesarean section? PMID- 8368566 TI - Cesarean section after maternal acetaminophen overdose. PMID- 8368567 TI - Rhabdomyolysis, acute renal failure, and the exaggerated lithotomy position. PMID- 8368568 TI - Drager ventilator failure. PMID- 8368569 TI - Methylprednisolone, head trauma, and brain protection. PMID- 8368570 TI - Cost saving with reusable pulse oximeter probes. PMID- 8368571 TI - Venovenous bypass and liver transplantation. PMID- 8368572 TI - Epidural test dose with lidocaine in obstetrics: why ask questions? PMID- 8368573 TI - A method to assist radial artery cannulation. PMID- 8368574 TI - An alternative approach for administering metered dose inhalers. PMID- 8368575 TI - Sensory testing in a rat sciatic nerve model. PMID- 8368576 TI - Additional evidence against a unitary site of volatile anesthetic action. PMID- 8368577 TI - An infusion pump that works in MRI. PMID- 8368578 TI - Saline versus water for epidural injection. PMID- 8368579 TI - American Society of Anesthesiologists 1993 Annual Meeting. Washington, D.C., October 9-13, 1993. Abstracts. PMID- 8368581 TI - Regulation of IgE synthesis by T cells and cytokines. AB - Human IgE synthesis is tightly regulated by cytokines. IgE production by normal B cells is specifically induced by IL-4, but requires additional, yet to be defined, signals that are provided by CD4+ T cells. Single surface IgM+ B cells can be induced to proliferate and switch to IgG4 and IgE producing cells, indicating that the induction of IgE synthesis by IL-4 and CD4+ T cells reflects direct isotype switching. Although IL-4 is the sole inducing cytokine of IgE synthesis known thus far, multiple cytokines modulate IL-4 induced IgE synthesis in vitro. IFN-alpha, IFN-gamma TGF-beta and IL-10 are inhibitory, whereas IL-5, IL-6 and TNF-alpha act synergistically with IL-4. Results obtained with animal models, as well as from clinical studies in the human have indicated that IL-4, IFN-alpha and IFN-gamma are operational in vitro. Cocultivation of B cells with allergen-specific CD4+ T cell clones producing high levels of IL-4 and IL-5, but normal to undetectable levels of IL-2 and IFN-gamma, following activation resulted in the synthesis of IgE, in the absence of exogenously added IL-4. These results indicate that aberrant ratio's of IL-4 and IFN-gamma production are sufficient for induction of IgE synthesis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368580 TI - Drugs responsible for anaphylactoid reactions in anaesthesia in the United Kingdom. PMID- 8368582 TI - The histamine H3 receptor: pharmacology and potential therapeutic applications. PMID- 8368583 TI - Mechanisms in IgE-dependent anaphylaxis to anesthetic drugs. AB - The discovery of IgE antibodies to neuromuscular blocking drugs, to thiopentone and narcotics, particularly morphine, reinforced earlier beliefs formed from skin test and other clinical findings that many "anaphylactoid" reactions to drugs were true type 1 immediate hypersensitivity reactions. Immunochemical studies established the fine structural specificities of the drug-reactive IgE antibodies and provided an explanation in molecular terms for a number of observed clinical cross-reactions. Subtleties in interpreting relationships between skin tests and IgE radioimmunoassays are pointed out and mechanisms of drug-induced mediator release, persistence of IgE antibodies and the nature of the sensitizing sources are discussed. PMID- 8368584 TI - Non specific interactions in anti-agent IgE-RIA to anesthetic agents. AB - The sensitivity of usual IgE-RIA for detecting seric anti-neuromuscular blocking drug (NMBD) IgE antibodies is low. Our group and other authors have proposed quaternary ammonium compounds other than NMBD for the preparation of sepharose solid drug phase. These compounds cannot be cyclohexenyl derivatives in order to prevent hydrophobic interactions with seric hydrophobic IgE. Allergic reactions against cyclohexenyl derivatives such as propofol could be linked to a non specific hydrophobic binding of the drug to hydrophobic seric IgE. Such hydrophobic IgE are seen in 30% of atopic subjects, in 41% of patients with drug allergy and in 100% of those allergic to propofol. The latter had also anti quaternary ammonium IgE in 5 out of the 8 cases studied. These NMBD antibodies could bind to the quaternary-ammonium ion of the lecithins from Diprivan micelles. PMID- 8368585 TI - Improved diagnosis of anaphylactoid reactions by measurement of serum tryptase and urinary methylhistamine. PMID- 8368586 TI - Diagnosis of IgE-dependent anaphylaxis to neuromuscular blocking drugs, thiopentone and opioids. AB - Although allergenic cross-reactivity of neuromuscular blocking drugs (NMBDs) is recognised clinically and has been firmly established at the serological and immunochemical levels, interpretation of in vitro inhibition findings for clinical purposes is not always straightforward. Points to be taken into account when considering serum IgE direct binding and inhibition results and when determining which NMBDs a patient may be sensitive to, include the relationship between in vitro potencies and clinical findings and the nature of the drug solid phase used for testing. It should also be remembered that the stimulating antigenic source for the patients' NMBD-reactive IgE antibodies is almost always unknown. A comparison of skin and IgE radioimmunoassay (RIA) tests for NMBDs in 29 patients is presented and difficulties involved in interpreting the results of both tests are discussed. Methods for increasing the detection of NMBD-reactive IgE antibodies are outlined. In screening sera of patients for IgE antibodies to thiopentone and morphine as well as NMBDs, multiple drug reactivities have been detected in a few subjects. Attention is drawn to defects in the existing thiopentone RIA although it is clear that the test is specific in patients who react to the drug. Addition of the serum tryptase assay to skin tests and IgE RIAs for NMBDs, thiopentone and morphine provides a powerful combination of diagnostic tests for the investigation of anaphylactoid reactions to anaesthetic drugs. PMID- 8368587 TI - Limits of interpretation of screening tests for anaphylactic shock to muscle relaxants. PMID- 8368588 TI - Concept and limitations of predictive tests in anaesthesiology. PMID- 8368589 TI - New concepts in the treatment of anaphylactoid reactions in anesthesia. PMID- 8368590 TI - [New concepts in allergo-anesthesia]. PMID- 8368591 TI - Drugs and other agents involved in anaphylactic shock occurring during anaesthesia. A French multicenter epidemiological inquiry. AB - An epidemiological inquiry was carried out in departments of anaesthesia and immunology in French University and General Hospitals, as well as among those who were already known to have an allergo-anaesthesia outpatient clinic. This inquiry aimed to find out how many patients had undergone diagnostic investigations after as well as an anaphylactoid reaction during an anaesthetic in 1990 and 1991, as well as the demographic data, the kind of assessment, the accident mechanism and the drugs involved. Twenty-one French centres replied to the questionnaire and a series of 1,585 patients tested over a two-year period was thus collected. There were three female patients to one male. The reactions occurred mostly in the adult (80%), but 9% were observed in children. Allergological tests for IgE dependent anaphylaxis were the skin tests (21 centres), combined with radioimmunological assays of specific serum antibodies to muscle relaxants (10 centres), propofol (9 centres), latex (5 centres), leukocyte histamine release (9 centres) and human basophil degranulation test (4 centres). The criteria for a positive result were the same for all centres. Among these 1,585 patients, 813 were recognized as having had a reaction of immunological origin (52%). The substances involved were identified in these 813 patients as being muscle relaxants (70%), latex (12.6%), hypnotics (3.6%), benzodiazepines (2.0%), opioids (1.7%), colloids (4.7%), and antibiotics (2.6%). Suxamethonium was responsible for 43% of the IgE-dependent reactions involving a muscle relaxant, vecuronium for 37%, pancuronium for 13%, alcuronium for 7.6%, atracurium for 6.8% and gallamine for 5.6%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368592 TI - The incidence and clinical features of anaphylactic reactions during anesthesia in Australia. AB - The details of 826 patients referred to an Anaesthetic Allergy Clinic over a 17 year period are described. 443 were classified as having severe immediate anaphylactic reactions and in the majority of these (263) a muscle relaxant was involved. In Australia, the most common cause of a reaction is alcuronium, which probably reflects usage, although it is the most commonly found to give a positive skin test in relaxant reactors. Suxamethonium and atracurium appear to have an incidence of reactions greater than predicted by market share and pancuronium and vecuronium appear safer both on incidence of reactions and on positive skin tests in reactors. The incidence of reactions is between 1:10,000 and 1:20,000 anaesthetics. Patients who react have greater incidence of allergy, atopy, asthma and previous reactions than non reactors. Previous exposure is usually apparent in reactors to induction agents but not muscle relaxants. Cardiovascular collapse is the most common presenting problem and is the only problem in 10%. Skin changes are the next most common and then bronchospasm which may be transient and is the hardest feature to treat. With an investigation protocol based on history, skin and RIA testing subsequent anaesthesia is usually safe. PMID- 8368593 TI - Keratan sulfate as a marker of articular cartilage catabolism and joint treatment in ponies. AB - Keratan sulfate (KS) is a glycosaminoglycan, distribution of which is confined mostly to hyaline cartilage. As such, it is a putative marker of hyaline cartilage catabolism. In experiment 1, a focal osteochondral defect was made arthroscopically in 1 radial carpal bone of 2 ponies, and in 2 other ponies, chymopapain was injected into the radiocarpal joint to induce cartilage catabolism. Sequential and concurrent plasma and synovial fluid concentrations of KS were measured, up to 13 months after induction of cartilage injury, to determine whether changes in KS concentrations reflected cartilage catabolism. In experiment 2, a large, bilateral osteochondral defect was made in the radial carpal bones of 18 ponies, which were subsequently given postoperative exercise and/or injected intra-articularly with 250 mg of polysulfated glycosaminoglycan (PSGAG). Medication was given at surgery, then weekly for 4 weeks. Blood samples were collected and synovial fluid was aspirated before surgery, when medication was given, and at postmortem examination (postoperative week 17). The KS concentration was measured in these fluids to determine whether changes in KS concentration indicated an effect of joint treatment. In experiment 1, the concentration of KS in synovial fluid was highest 1 day after joint injury, and the concentration in plasma peaked 2 days after joint injury. For ponies receiving chymopapain intra-articularly (generalized cartilage catabolism), a fivefold increase over baseline was observed in the concentration of KS in plasma (peak mean, 1.2 micrograms/ml), and a tenfold increase over baseline in synovial fluid (peak mean, 2.0 mg/ml) was observed. On average, these maxima were threefold higher than values in fluids of ponies with osteochondral defects (focal cartilage disease). In experiment 2, nonexercised ponies had lower KS concentration (as a percentage of the preoperative concentration) in synovial fluid than did exercised ponies at all postoperative times, and at postoperative week 17, this effect was significant (P < 0.05). This may be related to decreased turnover of KS in articular cartilage attributable to stall confinement and late increase in turnover related to exercise. Seventeen weeks after surgery, synovial fluid from exercised, medicated ponies had significantly (P < 0.05) higher KS content than did fluid from exercised, nomedicated ponies. This indicated that exercise, when combined with medication, may increase KS release from articular cartilage. Synovial fluid from medicated joints of nonexercised ponies had significantly (P < 0.05) lower KS concentration than did synovial fluid from nonmedicated joints of nonexercised ponies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368594 TI - Effects of sample collection and handling on concentration of osteocalcin in equine serum. AB - A commercially available radioimmunoassay kit for measurement of human osteocalcin was validated for use in horses. For accurate measurement of equine serum osteocalcin, blood samples may be collected at a temperature between 20 and 25 C, then centrifuged within 90 minutes; serum may be stored at -20 C in plastic tubes for up to 26 weeks. Serum may be thawed and refrozen up to 5 times without significant change in measured equine serum osteocalcin concentration. Assay sensitivity was 0.16 ng/ml. Recovery of bovine osteocalcin standard added to equine serum was linear. Intra-assay coefficient of variation (x 100) for 2 equine serum pools was 6.9 (mean +/- SD, 13.9 +/- 1.0 ng/ml) and 7.5 (10.6 +/- 0.8 ng/ml) %. Interassay coefficient of variation for 3 equine serum pools measured in 12 assays was 12.5 (16.1 +/- 2.0 ng/ml), 12.7 (11.5 +/- 1.5 ng/ml), and 24.6 (3.0 +/- 0.7 ng/ml) %. Dilutional parallelism was documented by assaying pooled equine serum at 4 dilutions and correcting the mean result for dilution. Significant change was not observed in equine serum osteocalcin concentration for various time-of-day blood sample collections in horses housed under continuous lighting. PMID- 8368595 TI - Coxofemoral joint laxity from distraction radiography and its contemporaneous and prospective correlation with laxity, subjective score, and evidence of degenerative joint disease from conventional hip-extended radiography in dogs. AB - A 3-year prospective study of large-breed dogs (4 months to 3 years of age) was conducted to evaluate the influence of radiographic positioning and age on coxofemoral joint (hip) laxity, subjective hip score, and development of degenerative joint disease (DJD). The dogs (n = 142) were breeder- or client owned and represented 14 breeds. With dogs under heavy sedation, hips were radiographed in the standard hip-extended position and in the new compression/distraction position at 4, 6, 12, 24, and 36 months of age. The standard hip-extended radiographic view was evaluated by 3 methods: subjective evaluation by a board-certified veterinary radiologist (WHR), according to the standard 7-point Orthopedic Foundation for Animals (OFA) scoring scheme (OFA/WHR); joint laxity quantitation, using the Norberg angle (NA) method; and subjective scoring by a veterinary orthopedic surgeon for radiographic evidence of DJD. The hips in the distraction radiographic view were evaluated for passive hip laxity, as measured by use of a unitless distraction index (DI). Results of the study indicated that at a specific age (4, 6, 12, 24, or 36 months), all methods of hip evaluation correlated with each other at a moderate level (P < 0.05). The strength of contemporaneous correlation tended to increase with age of evaluation. Longitudinally, the between-method correlations were usually significant (P < 0.05), but not at a sufficiently high level to permit reliable between-method prediction. Prospective intraclass (within-method) statistical analysis of the various hip-scoring methods indicated that DI was superior to NA and OFA/WHR in comparability of score over time. The intraclass correlation coefficient ranged from 0.55 to 0.91 for DI in contrast to 0.40 to 0.78 for NA, and 0.06 to 0.39 for OFA/WHR over the age intervals of the study. For reference, the highest Kappa of 0.39 for the subjective OFA/WHR scoring reflected a maximal level of agreement between time intervals, only slightly better than chance. The associated large error questions the predictive use of the 7-point, subjective hip-scoring scheme, particularly prior to the age of 2 years. PMID- 8368596 TI - Use of indirect enzyme-linked immunosorbent assay with hot saline solution extracts of a variant (M-) strain of Brucella canis for diagnosis of brucellosis in dogs. AB - An ELISA, using hot saline solution extracts (HSS) of a less-mucoid variant (M-) strain of Brucella canis as antigen, was developed for detection of antibodies against B canis in dogs. The test was applied to 177 field serum samples previously tested by use of the 2-mercaptoethanol rapid slide agglutination test, 2-mercaptoethanol-tube agglutination test, and agar gel immunodiffusion containing HSS and cytoplasmic antigens of B. canis. Results indicated that this ELISA seems to be highly specific (95.6%) and slightly less sensitive (93.8%). The HSS obtained from B canis wild-type RM 6/66 also have been used, but in our study, it seemed to be unsuitable for use in ELISA because of the high background values observed for sera with negative test results. PMID- 8368597 TI - Prevalence of atretic corpora lutea in ovaries of bovine fetuses. AB - Both ovaries from 88 bovine fetuses in the fifth month or later of gestation were studied histologically to determine the prevalence, origin, and time of appearance of atretic corpora lutea (ACL). Ovaries from 36 (41%) fetuses had ACL; fetuses < 6 months of gestation did not have ACL. Six fetuses had more than 25 ACL, but there was no apparent relationship between fetal age and number of ACL. Formation of ACL involved disintegration of the stratum granulosum of secondary follicles, concomitant with proliferation and invasion by vascularized elements of the theca. Fully developed ACL consisted of a large primary oocyte surrounded by a prominent zona pellucida and encased in a well-vascularized, largely thecal, fibrocellular wall. They measured approximately 0.5 to 1.0 mm in diameter. Empty, collapsed zona pellucidas were seen in many of the degenerating ACL. PMID- 8368598 TI - Serum immunoglobulin concentrations after feeding maternal colostrum or maternal colostrum plus colostral supplement to dairy calves. AB - Maternal colostrum or maternal colostrum plus colostral supplement, composed of a blend of lyophilized colostrum and dried whey, was fed to 32 Holstein calves as soon as possible after birth (mean +/- SEM = 2.0 +/- 0.2 hours) and, again, 12 hours later. Mean immunoglobulin concentration in colostrum was 59.2 mg/ml; mean immunoglobulin fraction in supplement was 11.4%. Serum immunoglobulin concentrations were measured at 0, 12, 24, 48, and 72 hours, and at 28 and 56 days. Hour/treatment interactions were significant for total immunoglobulin, IgG1, and IgM concentrations. Immunoglobulin concentrations were highest at 12 hours (total immunoglobulin, IgG1, IgM) or 24 hours (IgG2) in calves fed colostrum plus supplement, whereas all immunoglobulin concentrations were highest at 24 hours in calves fed maternal colostrum only. Peak mean immunoglobulin concentrations did not differ between treatments. Supplementation of colostrum did not increase peak mean serum immunoglobulin concentration, but did alter the serum concentration-time profile from 12 to 72 hours after birth. PMID- 8368599 TI - Immunoglobulins in stimulated tears of dogs. AB - Immunoelectrophoresis and single radial immunodiffusion were used to identify and measure tear immunoglobulin concentrations in 50 healthy dogs. Immunoglobulin A and IgG were detected in all samples analyzed, whereas IgM was not detected in any sample. Mean IgA concentration was 25.28 +/- 1.9 mg/dl, adult dogs (> 18 months) having significantly higher mean value. The IgA concentration related to age had significant (P < 0.006) positive correlation; mean IgG concentration was 23.10 +/- 1.72 mg/dl. Linear correlation analysis revealed significant (P < 0.0007) correlation coefficient between tear total protein and IgA concentrations. The IgA and IgG concentrations also were significantly (P < 0.0001) correlated when expressed as milligrams per 100 mg of protein. Relation with sex was not established for either immunoglobulin. PMID- 8368600 TI - Association between the effacing (eae) gene and the Shiga-like toxin-encoding genes in Escherichia coli isolates from cattle. AB - Two hundred ninety-six Escherichia coli isolates from feces or intestines of calves with diarrhea were hybridized with 7 gene probes. One probe (the eae probe) was derived from the eae gene coding for a protein involved in the effacement of the enterocyte microvilli by the group of bacteria called attaching and effacing E coli (AEEC), and 2 probes were derived from genes coding for the Shiga-like toxins (SLT) 1 and 2 produced by the verocytotoxic E coli (VTEC). The other 4 probes were derived from DNA sequences associated with the adhesive properties of enteroadherent E coli (EAEC) to cultured cells (the EAF probe for the localized adherence pattern, probes F1845 and AIDA-1 for the diffuse adherence pattern, and the Agg probe for the aggregative adherence pattern). Hybridization results for the eae probe were in agreement, for all but 1 of the 8 isolates, with previously published phenotypic results of microvilli effacement. The latter was previously reported as effacing the microvilli of calf enterocytes, but was eae probe-negative. Two classes of isolates hybridized with the eae probe. Members of a first class (60 isolates) additionally produced a positive signal with 1 or both of the SLT probes (VTEC-AEEC isolates). Isolates hybridizing with the eae and the SLT1 probes were the most frequent: 56 isolates (ie, 93% of all VTEC-AEEC). Members of the second class (10 isolates) failed to hybridize with either SLT probe (non-VTEC-AEEC isolates).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368602 TI - Immunologic changes in Ostertagia ostertagi-infected calves treated strategically with an anthelmintic. AB - Immunomodulation by Ostertagia ostertagi and the effects of strategic anthelmintic treatments were studied in 3 groups of 6 calves each: an infected group, inoculated with 100,000 third-stage larvae (L3)/calf at 1 and 28 days; an infected-treated group, similarly inoculated, but treated with ivermectin 9 days after each inoculation; and a noninfected control group. Calves were grazed on 2 previously clean pastures, with the infected and infected-treated calves sharing 1 pasture. All calves were inoculated at 12 weeks with Brucella abortus and infectious bovine rhinotracheitis vaccines, and at 13 weeks with a soluble O ostertagi L3 extract (SLE). Infected and infected-treated calves had lower blood lymphocyte responses to phytohemagglutinin than did control calves at 2, 4, and 14 weeks, whereas the infected calves had higher responses at 6 and 8 weeks (P < 0.05). Responses to pokeweed mitogen followed a similar pattern, whereas those to SLE were low in all calves. Infected and infected-treated calves had increased values of IgG1 to excretory-secretory antigens of L4 larvae, but no changes in the values of IgG1 to SLE. They also had lower values of IgG and IgM to B abortus and antibodies to infectious bovine rhinotracheitis at 13 weeks. The infected treated calves, however, had higher blood lymphocyte and monocyte counts and lower eosinophil count than did infected calves. They also had reduced abomasal mucosa thickness, abomasal wall weight, and abomasal lymph node weight than infected calves. It was concluded that O ostertagi causes nonspecific suppression of cellular and humoral immunity, hypersensitivity reactions coexisted with immunosuppression, and strategic anthelmintic treatments attenuated hypersensitivity reactions and initiated better immune responses. PMID- 8368601 TI - Serogrouping of Bacteroides nodosus isolates from 62 sources in the United States. AB - Bacteroides nodosus isolates from 62 sources in the United States were obtained from sheep with infectious foot diseases. Serotypic analysis of these isolates revealed 21 serotypes (designated I-XXI). These serotypes were compared with British and Australian/New Zealand B nodosus strains by use of reciprocal tube agglutination tests. These tests, as well as the cross-matching tube agglutination tests of the US serotypes, resulted in arranging the US serotypes into 11 serogroups, and comparing these serogroups with their Australian/New Zealand serogroup and British serotype counterparts. Three US serogroups and 1 additional British serotype had little or no relationship to any of the Australian/New Zealand serogroups A-H (the vaccine strains). One or more of these unrelated serogroups were found in 29% of the sources studied. The most frequently found US serotype was serotype XV at 29%. The most frequently found US serogroups were the serogroups analogous to serogroup B (43.5%) and serogroup H (37%); the other serogroups were found in 22.6% or less of the sources studied. Evaluation of 3 sources revealed that multiple serotypes in a single flock are common, multiple serotypes from a single lesion are possible, B nodosus isolates obtained from goats (unlike those from cattle) appear identical to the isolates obtained from sheep, and disease can appear in vaccinated animals, even in a flock that appears to be harboring only a single serogroup-B serotype (the serogroup for which there are 3 strains in the current vaccine). PMID- 8368603 TI - Skeletal muscle of cattle affected with progressive degenerative myeloencephalopathy. AB - Skeletal muscle from multiple sites of 6 cattle afflicted with progressive degenerative myeloencephalopathy was analyzed by transmission electron microscopy and compared with skeletal muscle taken from 2 clinically normal cattle (controls) similarly studied. Major changes in the affected muscle included abnormal myoneural junctions with redundant junctional folds that were abnormally long and branching, and occasionally separated from the synaptic site; multiple vacuoles of variable size clustered in subsarcolemmal positions and in rows between myofibrils; bizarre mitochondria with thin connecting stalks, large electron-dense bodies, and abnormal cristae; and cone-shaped projections of the sarcolemma. These findings indicate that myopathy is part of the progressive degenerative myeloencephalopathy phenotype. PMID- 8368604 TI - Sequential study of pancreatic structure and function during development of pancreatic acinar atrophy in a German shepherd dog. AB - Sequential assessments of pancreatic structure and function were performed on a female German Shepherd Dog bred from parents with exocrine pancreatic insufficiency (EPI), to monitor development of pancreatic acinar atrophy in this breed. Determinations of serum trypsin-like immunoreactivity (TLI), results of N benzoyl-L-tyrosyl-P-aminobenzoic acid test, fecal soy bean stimulation test (SST), and gross and histologic examinations of the pancreas did not provide evidence of exocrine pancreatic disease up to 13 months of age. However, electron microscopy revealed degenerative abnormalities of acinar cells that were already apparent at 6 weeks and became more extensive with age. Examination of the pancreas at 22 months of age also indicated no gross or histologic abnormalities, but electron microscopy revealed widespread degenerative changes, including dilatation of the rough endoplasmic reticulum and extensive fusion of zymogen granules affecting most of the acinar cells. Serum TLI concentration was markedly reduced at that time, indicative of EPI, but the dog remained healthy and results of the SST were normal. Within 1 month, the dog had developed clinical signs of EPI, and not only serum TLI concentration, but also results of the N-benzoyl-L tyrosyl-p-aminobenzoic acid test and SST were compatible with severe loss of exocrine pancreatic tissue. This loss was confirmed by gross and histologic examination of the pancreas at 25 months, which revealed typical features of pancreatic acinar atrophy, including scattered and disorganized exocrine cells in the small remnants of pancreatic tissue. These findings indicate that in German Shepherd Dogs, pancreatic acinar atrophy may involve interference with normal intracellular processing of zymogen granules, which precedes progressive and eventual rapid loss of exocrine pancreatic tissue. PMID- 8368605 TI - Effect of ranitidine on healing of experimentally induced gastric ulcers in ponies. AB - Thirty young ponies were examined endoscopically for evidence of gastric ulceration. Seven ponies had noninduced gastric ulcers present at the initial examination and were eliminated from the study. In an attempt to induce gastric ulcers experimentally, flunixin meglumine (1.1 mg/kg of body weight, IM, q 8 h) was administered for 7 days to the 23 ponies with endoscopically normal gastric mucosa. During the 7 days of flunixin administration, 11 ponies developed gastric ulcers that were appropriate for study. The 11 ponies were randomly allotted to 2 groups. Group-A (n = 5) and group-B (n = 6) ponies received ranitidine (4.4 mg/kg, PO, q 8 h) and corn syrup, respectively, until ulcers healed or for a maximum of 40 days. General anesthesia was induced every 3 to 5 days for visual evaluation of ulcer healing by use of a video endoscope. The earliest complete healing of gastric lesions observed in a corn syrup-treated pony was at 17 days. At 40 days, 3 of 5 and 3 of 6 ponies of the ranitidine and corn syrup-treated groups, respectively, had healed ulcers. Results of this study indicate that: noninduced gastric ulcers may be common in young ponies, flunixin meglumine may be effective in inducing gastric ulcers for gastric healing studies in young ponies, and ranitidine (4.4 mg/kg, q 8 h) is not significantly effective in accelerating healing of experimentally induced gastric ulcers in ponies under conditions of this study. PMID- 8368606 TI - Pharmacokinetics of digoxin administered to horses with congestive heart failure. AB - Nine horses with (naturally acquired) congestive heart failure were treated with 2.2 micrograms of digoxin/kg of body weight by the IV route, followed by 11 micrograms/kg administered orally every 12 hours thereafter. Furosemide was administered IV concurrently with IV administered digoxin every 12 hours. Serum concentration of digoxin was measured after the first (IV) and seventh (orally administered) dose. After IV administration, digoxin disposition was described by a 2-compartment model, with a rapid distribution phase (t1/2 alpha = 0.17 hour), followed by a slower elimination phase (beta = 0.096 +/- 0.055 h-1, t1/2 beta = 7.2 hours, where beta is the exponential term from the elimination phase of the concentration vs time curve). Bioavailability after oral administration was 21.2 +/- 10.8%. After the seventh orally administered dose, serum concentration of digoxin peaked 1 to 2 hours later, and was 1.9 +/- 0.7 ng/ml (mean +/- SD). In 4 horses, a second increase in serum digoxin concentration was observed 4 to 8 hours after the initial peak, which possibly was evidence of enterohepatic recycling of the drug. Response to treatment included reduction in heart rate, peripheral edema, and pulmonary edema, but these could not be attributed to the digoxin alone because the horses were treated concurrently with furosemide. PMID- 8368607 TI - Effect of age on theophylline pharmacokinetics in dogs. AB - Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition processes. Effect of age on the pharmacokinetics of theophylline was determined after IV administration of the drug to 10 groups of dogs at 1, 2, 3, 4, 8, 12, 16, 24, 52, and 104 weeks of age. Plasma theophylline concentration curves for all groups were adjusted to a biexponential kinetic, with rapid initial distribution phase and slower elimination phase. It also was noticed that young dogs have a slower elimination half-life (1 week old, t 1/2 beta = 987 minutes) than do older animals (8 weeks old, t 1/2 beta = 138 minutes). The values then plateaued until 16 weeks of age, increasing slightly at more advanced age (104 weeks old, t 1/2 beta = 282 minutes). A similar pattern was followed with respect to clearance (1-week-old pups, Cl = 1.17 ml/min/kg of body weight), which increased progressively to reach a value of 7.09 ml/min/kg at 16 weeks of age, then decreased to 3.5 ml/min/kg at 104 weeks of age. Volume of distribution beta, in relation to body weight, was not significantly different between age groups (between 1.2 and 1.6 L/kg; P < or = 0.03). Theophylline biotransformation mechanisms may be mainly responsible for Cl and t 1/2 beta variations. This leads us to suggest that quantitative and qualitative modifications in the P-450 mono-oxygenase system are responsible for the variations observed in pharmacokinetic variables of theophylline between dogs of different ages. These findings may have clinical relevance with regard to therapeutic range of theophylline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368608 TI - Effect of polysulfated glycosaminoglycan on osteoarthritic equine articular cartilage in explant culture. AB - Middle carpal cartilage explants from 4 horses with mild osteoarthritis involving that joint were maintained in tissue culture to test the effects of a polysulfated glycosaminoglycan (PSGAG) on proteoglycan synthesis and degradation. Cultures were exposed to 0.025 or 25 mg of PSGAG/ml for 48 hours, after which the medium was replaced with medium containing similar doses of PSGAG and 35S. Subsequently, the sulfated proteoglycan content of the medium and extracts of the explants was measured. Gel filtration chromatography was used to estimate the size and to purify the principal, large proteoglycan monomer, which was further characterized by digestion, using glycosidic enzymes. In a second experiment, explants were incubated with 35S for 48 hours, and were subsequently exposed to the same concentrations of the PSGAG for an additional 48 hours. The amount of remaining labeled proteoglycan was determined for culture medium and cartilage extracts. Gel filtration chromatography was used to assess the hydrodynamic size of the large proteoglycan monomer. Aliquots of proteoglycans from the second experiment were incubated in high-molecular weight hyaluronate and chromatographed to assess reaggregation. Polysulfated glycosaminoglycan caused a significant (P < or = 0.04) decrease in sulfated proteoglycan synthesis by cartilage explants. Radioactive proteoglycan content in explants labeled prior to exposure to PSGAG were similar. Large proteoglycan monomer size was similar in both experiments (median partition coefficient [KAV] = 0.40), and was not influenced by PSGAG treatment. Prelabeled explants exposed to hyaluronate and chromatographed under associative conditions had similar proportions of the radiolabel eluting as proteoglycan aggregate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368609 TI - Ibuprofen treatment of endotoxin-induced mastitis in cows. AB - Ibuprofen treatment was compared with saline solution treatment in an endotoxin induced experimental model of bovine mastitis. Acute mastitis was induced in healthy lactating Holstein cows (n = 12) by intramammary inoculation of 1 mg of Escherichia coli 026:B6 lipopolysaccharide in a single quarter per cow. Cows were assigned at random to ibuprofen (25 mg/kg of body weight, IV, n = 6) or 0.9% sodium chloride solution control (1.25 ml/kg, IV, n = 6) treatment groups. Ibuprofen or saline solution was administered once, 2 hours after endotoxin administration. The clinical course of endotoxin-induced mastitis and hematologic, clinical biochemical, and plasma mineral changes were monitored and compared between ibuprofen-treated and control cows. Clinical monitoring and blood sample collection were performed at 0, 2, 4, 6, 8, 12, 24, 48, 96, and 192 hours after endotoxin challenge. Rectal temperature and heart and respiratory rates were significantly (P < or = 0.05) increased in saline treated cows, compared with cows treated with ibuprofen. Blood eosinophil count and serum phosphorus, sodium, and total carbon dioxide concentrations were significantly (P < or = 0.05) decreased in saline-treated cows, compared with cows treated with ibuprofen. Ibuprofen treatment did not significantly change ruminations per minute, electrical conductivity of milk, quarter size, or quarter inflammation. The remaining hematologic, serum biochemical, plasma mineral, and coagulation values also were not changed significantly in response to ibuprofen treatment. Untoward effects attributed to ibuprofen administration were not observed. These results indicate that ibuprofen may provide empiric relief of clinical signs of coliform-induced mastitis. PMID- 8368610 TI - Pharmacokinetics of ibuprofen in lactating dairy cows. AB - The pharmacokinetics of ibuprofen were studied in 6 adult lactating dairy cows after a single IV or oral administration of ibuprofen (25 mg/kg of body weight). Ibuprofen concentrations in milk and serum were analyzed by use of high performance liquid chromatography. The lower limit of detection of the ibuprofen assay was 50 ng/ml. Serum ibuprofen concentration-time curves after IV administration best fit an open two-compartment model. Harmonic mean volume of distribution at steady state was 0.14 (range, 0.12 to 0.17) L/kg, elimination half-life was 1.55 (range, 1.33 to 1.73) hours, and total clearance was 86.2 (range, 68.8 to 106.2) ml/kg/h. Harmonic mean oral bioavailability was 99% (range, 79 to 112). Adverse effects were not observed in cows given ibuprofen. PMID- 8368611 TI - Effects of a 44-day administration of phenobarbital on disposition of clorazepate in dogs. AB - The disposition of clorazepate, a benzodiazepine anticonvulsant, was determined in dogs after administration of a single oral dose of clorazepate (2 mg/kg of body weight) and after oral administration of clorazepate (2 mg/kg, q 12 h) concurrently with phenobarbital (5 mg/kg, q 12 h) for 44 consecutive days. Serum concentrations of nordiazepam, the active metabolite of clorazepate, were measured. After a single oral dose of clorazepate, maximal nordiazepam concentrations ranged from 569.6 to 1,387.9 ng/ml (mean, 880.2 +/- 248.9 ng/ml) and were detected 16.8 to 131.4 minutes (mean, 85.2 +/- 36 minutes) after dosing. After administration of phenobarbital for 44 consecutive days, maximal nordiazepam concentrations were significantly (P < 0.01) lower, ranging from 209.6 to 698.5 ng/ml (mean, 399.3 +/- 155.6 ng/ml) at 68.4 to 145.8 minutes (mean, 93 +/- 25.8 minutes) after dosing. Mean area under the curve (AUC) on day 1 (mean, 3.37 +/- 0.598 ng.min/ml) was significantly (P < 0.001) greater than AUC on day 44 (1.66 +/- 0.308 ng.min/ml). Oral clearance was significantly (P < 0.01) greater on day 44 (12.44 +/- 2.55 ml/min/kg), compared with that on day 1 (6.16 +/- 1.35 ml/min/kg). Values for area under the first moment curve, oral volume of distribution, mean residence time, and elimination half-life were not significantly altered by concurrent administration of phenobarbital. Administration of phenobarbital altered the disposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval was significantly reduced. Adequate control of seizures in epileptic dogs, therefore, may require higher dosages of clorazepate when it is coadministered with phenobarbital. PMID- 8368612 TI - Development to blastocysts of one- to two-cell equine embryos after coculture with uterine tubal epithelial cells. AB - Development of 1- to 2-cell in vivo fertilized equine embryos cultured with or without uterine tubal epithelial cells (UTEC) was studied. One- to 2-cell embryos (n = 26) were collected surgically from the uterine tubes of pony mares 1 day after ovulation. Four- to 8-cell embryos (n = 9) were collected 2 days after ovulation. Presumptive zygotes and 2-cell embryos were cultured with (n = 17) or without (n = 9) UTEC, and all 4- to 8-cell embryos were cocultured with UTEC as positive controls. Uterine tubal epithelial cells were used as cell suspensions within 2 weeks after initiation of cultures. Embryos were cultured to blastocysts or until the embryo had morphologic degeneration. Six presumptive zygotes failed to cleave in vitro. Development to blastocysts of 1-cell (4 of 11) and 2-cell (2 of 6) embryos cocultured with UTEC was similar. Coculture of 1- to 2-cell embryos with UTEC significantly (P = 0.05) improved development to blastocysts, compared with culture in medium alone (35 vs 0%, respectively); however, development to blastocysts of 1- to 2-cell embryos cocultured with UTEC was less (P < 0.025) than that of 4- to 8-cell embryos cocultured with UTEC (35 vs 89%, respectively). PMID- 8368613 TI - Functional variation in endogenous and exogenous immunoglobulin binding to bovine neutrophils relative to parturition. AB - Ten healthy first- and second-lactation Holstein cows were observed from 1 week before to 1 week after calving and at postpartum day 30 to determine polymorphonuclear neutrophil (PMN) functional variation and immunoglobulin binding profiles. Blood and mammary PMN were obtained 3 times weekly and within 24 hours of calving. Functional traits measured included phagocytosis of Staphylococcus aureus and in vitro chemotaxis through micropore filters in a Boyden chamber. Additionally, PMN were evaluated for endogenous binding of IgG1, IgG2, IgA, and IgM before and after in vitro chemotaxis. Exogenous binding of the same isotypes was determined after incubation in pooled colostrum, purified immunoglobulin, and pooled sera. Phagocytosis results indicated a significant and transient increase in percentage of milk PMN with associated, rather than phagocytosed, bacteria for 1 week after calving. Blood PMN phagocytosis was not significantly different during this period. Though total chemotaxis was essentially unchanged, the percentage of PMN that were unable to complete migration increased substantially on the day of calving, an effect that disappeared by postpartum day 4. A significant (P < 0.01) positive correlation (r = 0.29) between percentage of PMN migrating completely through the micropore filter and percentage of blood PMN with associated bacteria was observed. Changes were not observed in endogenous immunoglobulin binding, with the exception of a peak in relative fluorescence intensity for IgG1 on the day of calving; this disappeared within 2 days after calving. Correlations between relative intensities of IgG2 and IgM, and percentage of mammary neutrophils phagocytosing were 0.37 and 0.70.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368614 TI - Isolation and characterization of porcine milk lactoferrin. AB - We purified porcine whey lactoferrin by affinity chromatography on a heparin Sepharose column, followed by high-performance liquid chromatography. Molecular mass of purified lactoferrin (PLF) is 78,000 daltons. The iron-binding activity of PLF had a UV/visible-light absorption spectrum indistinguishable from that of human and bovine lactoferrins (absorbance ratio [465 nm/280 nm] approx 0.046). The growth ratio of WIL-2 cells in PLF-supplemented medium is 70% of that in serum-containing medium. The aforementioned characteristics are similar to those of human and bovine lactoferrins. Immunoblot analysis, using polyclonal antibody raised in rabbits against porcine whey lactoferrin, revealed high specificity for PLF, and low cross-reactivity with commercial human and bovine lactoferrins. PMID- 8368615 TI - Comparison of 0.9, 3.6, and 7.2% NaCl for correction of experimentally induced hypochloremic, hypokalemic metabolic alkalosis in sheep. AB - Nine adult female sheep were each surgically fitted with an Ivan and Johnston reentrant cannula in the cranial part of the duodenum just distal to the pylorus. By diversion (loss) of abomasal outflow, this model has been shown to consistently induce hypochloremic, hypokalemic metabolic alkalosis, accompanied by hyponatremia and dehydration. Each sheep was subjected to 3 treatment trials, each preceded by a 24-hour prediversion period, and a diversion period during which a syndrome of hypochloremia (68 +/- 2 mEq/L), hypokalemia, hyponatremia, and metabolic alkalosis was induced. Development of this syndrome was attributable to losses of large amounts of acid and electrolytes in the abomasal effluent. Mean total electrolyte contents of the effluent were: Cl-, 650 +/- 27 mEq; Na+, 388 +/- 23 mEq; and K+, 123 +/- 12 mEq, with total volume loss ranging from 3.6 to 10.0 L of gastric contents and pH ranging from 3 to 5. Decreases in plasma electrolyte concentrations also can be attributed to decreased intake, because anorexia developed shortly after the onset of diversion. Electrolyte losses in urine during diversion were minimal for Cl- (mean +/- SEM, 12.0 +/- 5.1 mEq), but were greater for Na+ (124.2 +/- 14.5 mEq) and K+ (185.1 +/- 31.2 mEq). Treatments consisted of 0.9% NaCl (300 mosm/L), 3.6% NaCl (1,200 mosm/L), and 7.2% NaCl (2,400 mosm/L) administered over a 2-hour period, with the administered volume determined by the estimated total extracellular fluid Cl- deficit. Significant difference was not found among treatments, with all solutions resulting in return of clinicopathologic and physical variables to prediversion values within 12 hours of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368616 TI - Normal laparoscopic anatomy of the bovine abdomen. AB - Three laparoscopic procedures were performed on each of 6 adult Jersey cows in the first trimester of gestation to describe normal laparoscopic anatomy of the bovine abdomen. Also, a technique for laparoscopy of the cranioventral portion of the abdomen was described. Right paralumbar fossa, left paralumbar fossa, and cranioventral midline laparoscopy were performed 72 hours apart of each cow. Physical examination findings, CBC, serum biochemical analysis, and peritoneal fluid analysis before and 72 hours after the first surgery were used to assess the effects of the procedures on the cows. Exploratory celiotomy was performed 2 weeks after the last laparoscopy. The cows were then reexamined 6 weeks after the last procedure. The t-test for paired data was used for statistical analysis; the level of significance was P < 0.05. Laparoscopy was performed without complication in all cows. Adverse effects of laparoscopy, individually or serially, were not observed. Significant differences were not found between CBC, serum biochemical, and peritoneal fluid variables taken before and 72 hours after surgery. PMID- 8368617 TI - Evaluation of bending strength of five interdental fixation apparatuses applied to canine mandibles. AB - Strength in bending was determined for interdental fixation apparatuses applied to hemimandibles obtained from 24 canine cadavers. Hemimandibles were osteotomized perpendicular to the long axis between the third and fourth premolars, and segments were stabilized with 1 of 5 interdental fixation apparatuses: Erich arch bar (EAB, n = 6); Stout loop (SL, n = 6); acrylic (A, n = 6); Stout loop and acrylic (SLA, n = 24); and Erich arch bar and acrylic (EABA, n = 6). Ultimate strengths (mean +/- SEM) of EAB, SL, A, SLA, and EABA were 395 +/- 48; 523 +/- 57; 1,106 +/- 102; 1,306 +/- 156; and 2,707 +/- 504 N.m, respectively. Stiffness (mean +/- SEM) of EAB, SL, A, SLA, and EABA were 2,944 +/ 357; 6,322 +/- 2,201; 16,010 +/- 5,017; 15,777 +/- 1,026; and 27,079 +/- 5,576 N.m/radian, respectively. Yield strengths (mean +/- SEM) of EAB, SL, A, SLA, and EABA were 66 +/- 6; 264 +/- 19; 911 +/- 126; 1,114 +/- 159; and 1,855 +/- 401 N.m, respectively. There were no significant differences in acrylic weight, cross sectional area of the acrylic, or area moment of inertia of acrylic at the osteotomy site among A, SLA, and EABA; and there were no significant differences in osteotomy surface area and area moment of inertia at the osteotomy site among all apparatuses (P > 0.05). The EABA apparatus had significantly higher mean ultimate strength, mean stiffness, and mean yield strength compared to other interdental fixation apparatuses. There were no significant differences in the mean ultimate strength, mean stiffness, or mean yield strength between EAB and SL (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368618 TI - Scanning electron microscopy of intraocular lenses that had been implanted in dogs. AB - Scanning electron microscopy was used to evaluate changes on the surfaces of polymethylmethacrylate (PMMA), silicone, and polyhydroxyethylmethacrylate (HEMA) intraocular lenses (IOL) that had been implanted in the anterior chambers of the right eyes of 15 dogs. Five dogs received PMMA IOL; 5 dogs received silicone IOL; and 5 dogs received HEMA IOL. Twenty-eight days after surgery, the IOL were removed and processed for scanning electron microscopy. Nonimplanted IOL of each type were processed identically for comparison. Implanted PMMA IOL had significantly more debris and macrophages on their surfaces than did silicone IOL or HEMA IOL. Silicone IOL had significantly less fibrin deposition than did PMMA or HEMA IOL. Silicone IOL had surface defects attributable to handling by surgical instruments. Implanted HEMA IOL had multiple pits that appeared to be caused by biodegradation. PMID- 8368619 TI - Effect of homologous fibrin adhesive on callus formation and extracortical bone bridging around a porous-coated segmental endoprosthesis in dogs. AB - Modular, porous-coated, titanium segmental endoprostheses were implanted bilaterally in the femoral diaphysis of 7 adult mixed-breed dogs. Autogenous bone graft in particle form was placed around the implant and bone. In 1 limb, homologous fibrin adhesive was mixed with the graft in situ before soft tissue closure. The contralateral limb was grafted in identical manner, but without fibrin adhesive, and served as a control. Radiography was performed immediately after surgery and 1, 2, 3, 4, 6, 8, 10, and 12 weeks later to assess callus area and bone remodeling. At 12 weeks, dogs were euthanatized and bone/implant fixation strength was tested under torsion and compared with values for 6 in vitro controls. Histomorphometric and microradiographic analyses of transverse sections of the distal portion of the implanted femurs were performed. Radiographic callus area was significantly (P < 0.05) smaller in the femurs grafted with fibrin adhesive, compared with the contralateral control. New bone formation (21.4 +/- 1.8% vs 19.2 +/- 2.4%), unlabeled bone (64.8 +/- 3.0% vs 67.9 +/- 4.2%), porosity (13.9 +/- 0.7% vs 12.9 +/- 0.8%), and bone ingrowth into the porous coating (10.3 +/- 0.9% vs 10.0 +/- 1.2%) were not significantly different between fibrin- and nonfibrin-grafted implants, respectively. There were no significant differences in torsional strength of implant fixation between the fibrin- and nonfibrin-grafted femurs or between the in vivo implanted femurs and the in vitro controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368620 TI - Use of scintimetry to assess effects of exercise and polysulfated glycosaminoglycan on equine carpal joints with osteochondral defects. AB - Combined blood pool and delayed images produced by use of 99mTc-methylene diphosphonate (99mTcMDP) were evaluated as an objective measurement of the response of equine joints with osteochondral defects to postoperative exercise and intra-articularly administered polysulfated glycosaminoglycan (PSGAG). Osteochondral defects (approx 2.4 x 0.9 cm) were induced arthroscopically in the dorsodistal radial carpal bones of 18 ponies. These ponies were randomized (while balancing for age [range 2 to 15; median, 5.0; mean, 5.1 years]) to 2 treatment groups. Nine ponies were assigned to be exercised, and 9 were stall-rested. Six ponies in each group were administered PSGAG (250 mg) in 1 joint (medicated) and lactated Ringer's solution (LRS) in the contralateral joint. The 3 remaining ponies in each group were administered LRS in both joints (nonmedicated). Medication was given at surgery, then weekly for 4 weeks. The exercise protocol (begun at postoperative day 6 and conducted twice daily) started with 30 minutes walking (approx 0.7 m/s), and, by postoperative month 3, the ponies were being walked for 15 minutes and trotted (approx 1.6 m/s) for 25 minutes. Simultaneous dorsal images of both carpi were made 2 to 3 minutes after IV administration of 99mTcMDP (blood pool image) and 90 to 120 minutes later (delayed image). Scintimetry, in counts per minute per pixel per millicurie, was done before, and at 1, 2, 4, 8, 10, 13, and 17 weeks after surgery, prior to euthanasia. Radionuclide uptake on blood pool images decreased faster than that on delayed images, in which uptake remained high for 17 weeks. This indicated that bone was metabolically active for at least 17 weeks after surgery. Exercise significantly (P < 0.05) decreased uptake on the blood pool images of medicated joints up to 1 month after surgery. Thus, exercise (in the presence of PSGAG) probably had a transient, beneficial effect on soft tissues of the joint. Exercise, without PSGAG, promoted increased bone remodeling, because the highest uptake on delayed images was observed in exercised, nonmedicated ponies up to 3 months after surgery. This was consistent with development of osteoarthritis in these ponies. Medication alone stimulated bone remodeling, and data indicated that an identical effect may take place in contralateral LRS-injected joints, because of systemic circulation of the drug. However, the combination of exercise and medication appeared to moderate the independent effects of each. The combination of exercise and medication in individual joints resulted in notably (P < 0.05) decreased bone remodeling.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8368621 TI - Death due to asthma. New insights into sudden unexpected deaths, but the focus remains on prevention. PMID- 8368622 TI - Allergen-specific treatment for asthma: III. PMID- 8368623 TI - Safety of bronchoalveolar lavage in patients with adult respiratory distress syndrome. AB - Although shown to be safe in many other lung disorders, the safety of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) in critically ill patients with adult respiratory distress syndrome (ARDS) remains unproven. We conducted a prospective study to evaluate the safety of BAL in patients with ARDS. There were 438 patients with ARDS at our institution during the study period. Of these, 110 underwent FOB and BAL for either research or clinical purposes. Data were collected at baseline, at 5-min intervals during the procedure, and 1 h after the procedure. We did not detect any statistically or clinically significant changes in PaO2/FlO2, mean arterial pressure, heart rate, peak inspiratory pressure, or static thoracic compliance after the procedure. A small decrease in SaO2 occurred after BAL. Although this change was statistically significant, the magnitude was not of clinical importance. Five patients (4.5%) had transient arterial oxygen desaturation to < 90% during FOB and one patient (0.9%) experienced desaturation to < 80%. There were no prolonged episodes of severe hypoxemia. No serious bleeding occurred. One pneumothorax developed during the procedure. No deaths occurred that were related to the procedure. We conclude that FOB and BAL can be performed safely and are reasonably well-tolerated in patients with ARDS. PMID- 8368624 TI - Modes of tracheal gas insufflation. Comparison of continuous and phase-specific gas injection in normal dogs. AB - Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination accomplished by conventional mechanical ventilation, primarily by reducing the anatomic (series) dead space volume. Dead space proximal to the catheter tip can be reduced by two methods. Fresh gas introduced at the carinal level during inspiration may effectively "bypass" the upper airway. Alternatively, proximal dead space can be "washed out" with fresh gas during expiration to reduce CO2 rebreathing. We examined these two modes of TGI-aided dead space reduction in nine paralyzed normal dogs receiving conventional mechanical ventilation and compared these results to those obtained with a catheter that delivered fresh gas continuously at the same flow rate, thereby accomplishing both bypass and washout. Total inspired tidal volume and cycling frequency were held constant. Differences in CO2 elimination efficiency among the TGI modes were flow dependent. Continuous catheter flow at 5 or 10 L/min reduced PaCO2 and physiologic dead space fraction (VD/VT) more than either proximal bypass or end expiratory washout (p < 0.001). At the same catheter flow settings expiratory washout tended to improve VD/VT more than did inspiratory bypass. Under the conditions tested, constant tracheal insufflation of fresh gas improves alveolar ventilation by mechanisms that include, but are not limited to, a functional reduction in the dead space proximal to the catheter tip. PMID- 8368625 TI - Optimizing alveolar expansion prolongs the effectiveness of exogenous surfactant therapy in the adult rabbit. AB - We evaluated four ventilator patterns after the administration of 80 mg/kg bovine lipid extract surfactant (LES) to anesthetized, paralyzed, saline-lavaged New Zealand white rabbits. Two ventilator types were compared: high frequency oscillatory ventilation (HFO) versus conventional mechanical ventilation (CMV), each at high (HI) and low (LO) end-expiratory lung volumes (EELV); n = 6, each group; treatment duration = 4 h. Target PaO2 ranges were > 350 mm Hg for groups with high EELV (i.e., HFO-HI and CMV-HI) and 70 to 100 mm Hg for those with low EELV (i.e., HFO-LO and CMV-LO). Ventilator pressures were limited to < or = 39/9 cm H2O in the CMV-HI group. Five of six CMV-HI-treated animals did not maintain target PaO2 levels. Both ventilator type and strategy influenced outcome significantly. Animals managed with HFO had higher mean arterial pressures (p = 0.004), lower mean airway pressures (Paw) (p < 0.00008) and HCO3- requirements (p < 0.02), larger inflation (p = 0.003) and deflation (p < 0.00001) respiratory system volumes at 10 cm inflation pressure, and higher lung lamellar body (p = 0.0006) and lavage fluid (p = 0.003) phospholipid quantities than did CMV-treated animals. The deflation P-V curve (p = 0.0004), lamellar body (p < 0.00001) and lavage fluid (p = 0.0002) phospholipid levels were superior after the high EELV strategy. We conclude that ventilator pattern strongly influences exogenous surfactant efficacy. Benefits arise from keeping EELV high enough to prevent atelectasis and using small (approximately 2 ml/kg) tidal volumes to prevent overdistension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368626 TI - Fast versus slow ventilation for neonates. AB - To investigate the effect of ventilation rate on respiratory mechanics, 21 neonates ventilated in the neonatal period for various reasons were studied while being ventilated at 30 and 80 breaths/min. Dynamic respiratory system elasticity (ERS), dynamic respiratory system resistance (RRS), and alveolar pressure at end expiration (EEP) were calculated by using multilinear regression to fit the equation of motion of a linear single-compartment model. Technically satisfactory data were obtained from 13 neonates. With the fast ventilation rate, tidal volume and RRS decreased by a mean of 41.3% (p < 0.01) and 17.5% (p < 0.01), respectively, ERS and EEP increased by a mean of 8.3% (p < 0.05) and 22.2% (p < 0.01), respectively. Fast ventilation produced a shorter effective time constant during expiration, limiting the changes in EEP and, hence, in end-expiratory lung volume. The same changes in respiratory mechanics were also observed in neonates who did not show an increase in EEP even at high frequency. These neonates had a high elastance and time constant short enough to ensure adequate lung emptying. These results suggest that the respiratory mechanics of ventilated neonates are frequency dependent and that neonates with higher ERS, such as those with hyaline membrane disease, can cope with fast rate ventilation without developing dynamic hyperinflation. PMID- 8368627 TI - Tidal volume measurements in newborns using respiratory inductive plethysmography. AB - Respiratory inductive plethysmography (RIP) is a well-accepted noninvasive technology for monitoring breathing patterns in adults. Prior attempts to calibrate this device in babies have been fraught with technical difficulties, thereby limiting applications in this population. Recently, a new method, qualitative diagnostic calibration (QDC), has been shown to provide accurate calibration of tidal volume in adults. The QDC method is based upon principles of the isovolume maneuver and carried out during natural breathing without specialized respiratory maneuvers or postural changes. We calibrated RIP with QDC in the supine posture and compared tidal volume (VT) measured with RIP to VT by a face mask-pneumotachograph (PNT) in 21 healthy full-term newborns in supine and prone postures. Eleven of the babies were calibrated during active sleep and 10 in quiet sleep. The mean VT in the supine and prone postures were 19 and 25 ml, respectively. In the supine and prone postures, weighted mean difference between RIP (VT) and PNT (VT) and 95% confidence intervals were -0.05 ml (-0.27, 0.18) and -0.32 ml (-0.08, 0.55), respectively. There was no difference in the accuracy of RIP relative to PNT calibrated during active sleep when thoracoabdominal incoordination was present or quiet sleep when it was not in either the supine or the prone postures. Therefore, in full-term infants, RIP calibrated with QDC solely in the supine posture provides clinically acceptable measurements of VT in both supine and prone postures. PMID- 8368628 TI - Effect of cocaine in early gestation. Physiologic responses to hypoxia in newborn rabbits. AB - To investigate the effect of prenatal cocaine on the physiologic responses to hypoxia, we evaluated ventilation, oxyhemoglobin saturation, and pulse rate at 0.21 FIO2 (baseline) and in response to 20-min exposure to either 0.15 or 0.08 FIO2 on Days 4 to 6 of life in 31 unanesthetized New Zealand white rabbit pups born to cocaine-exposed (30 mg/kg/day of subcutaneous cocaine HCl injection from Days 7 to 15 of a 32-day gestation) or free-fed (injection of sterile water) does. We found that baseline ventilation (measured by dual-sidearm pneumotachograph from the plethysmograph), SaO2 (measured by pulse oximeter), and pulse rate did not differ significantly between cocaine-exposed and free-fed pups. At 0.15 FIO2, cocaine-exposed pups had increased VI (p < 0.0005), VT (p < 0.0005), and VT/TI (p < 0.0005) compared with free-fed pups, but no significant difference in f, TI, TE, TI/TT, SaO2, or pulse rate. At 0.08 FIO2, cocaine exposed pups had increased VI (p = 0.001), VT/TI (p = 0.021), and TE (p = 0.023) compared with free-fed pups, due primarily to the effects in the first 10 min of hypoxic exposure. However, differences in group response were less apparent than at 0.15 FIO2, with a sustained ventilatory response on prolonged exposure to 0.08 FIO2 among free-fed pups but not cocaine-exposed pups. Further, SaO2 (p < 0.0005) and pulse rate (p = 0.012) were significantly lower among cocaine-exposed pups compared with free-fed pups, particularly after 10-min exposure to 0.08 FIO2 when VI was equivalent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368629 TI - Influence of sleep on genioglossus muscle activation by negative pressure in normal men. AB - An important mechanism controlling genioglossus (GG) muscle activity is the reflex response to negative airway pressure. We hypothesize that this reflex response may be lost during sleep and believe that this loss may be important in the pathogenesis of airway collapse during sleep. Thus, we determined the effect of non-rapid eye movement (NREM) sleep on the GG electromyogram (EMG) response to brief (0.2 to 0.6 s) episodes of negative pressure generation (NPG) in the upper airway of six normal subjects. Up to 100 NPGs (mean 58 +/- 12) were recorded both awake and during stable NREM sleep. During wakefulness, the change in GG moving time average EMG from basal to peak levels (during NPG) was 17.1 +/- 2.5 au (a 154 +/- 22% increase above basal levels). This response was markedly reduced during NREM sleep (2.7 +/- 1.2 au; p < 0.01). The latency of the GG EMG response was 53.8 +/- 11.5 ms during wakefulness (n = 6), but much longer during sleep (132.7 +/- 24.5 ms; n = 3; p < 0.03). We conclude that in normal subjects (1) the GG muscle responds to negative airway pressure by reflex activation during wakefulness, and (2) this reflex activation is reduced or lost during NREM sleep. We speculate that loss of this mechanism during sleep may contribute to pharyngeal collapse in obstructive apnea patients. PMID- 8368630 TI - Pharyngeal narrowing and closing pressures in patients with obstructive sleep apnea. AB - Based on previous studies, we hypothesized that the pharynx collapses at multiple sites in most patients with obstructive sleep apnea (OSA). The purpose of this study was to document, in a population of apneic subjects, the site(s) of narrowing and closing pressure of the hypotonic pharynx. We endoscopically examined the pharynx in 45 OSA patients during sleep while they received nasal continuous positive airway pressure (CPAP), which produces hypotonia of pharyngeal muscles. Intrapharyngeal images and pressures were obtained at the end of expiration during single-breath tests (SBT). The fractional narrowing (FN) of each pharyngeal segment (nasopharynx, oropharynx, and hypopharynx) was calculated as the relative change in area when nasal airway pressure was reduced from a pressure that held the pharynx fully distended to the pressure at which the airway closed. The frequency distribution of FN for the nasopharynx was skewed toward larger values, and the frequency was relatively evenly distributed for the oropharynx and hypopharynx. A site having FN greater than 0.75 was defined as a site of primary narrowing, and a site showing FN 0.25 to 0.75 was defined as a site of secondary narrowing. The nasopharynx was a site of primary narrowing in 80% of patients, and two or more sites of narrowing were commonly observed (82%). Four categories of combined narrowing were identified: (1) primary narrowing only at the nasopharynx (18%); (2) primary narrowing at the nasopharynx plus other sites of secondary narrowing (40%); (3) primary narrowing at the nasopharynx plus other sites of primary narrowing (22%); and (4) other patterns (20%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368631 TI - Changes in diaphragmatic EMG activity during sleep in space. AB - It remains unknown how increased upper airway resistance (UAR) during sleep could be a function of gravity. We therefore conducted quantitative evaluation of the gravitational influence on diaphragmatic EMG activity (EMGdi) in an astronaut to estimate the effect of UAR in space. EMGdi was recorded by paired surface electrodes on the ground (control, C) and abroad a short-term space mission (space, S) for 30 consecutive h. Mean EMGdi recorded during quiet breathing in wakefulness was assigned the value of 100. EMGdi in C was significantly enhanced in all sleep stages compared with that while awake in the supine position (mean +/- SD, 230 +/- 23.2% in non-rapid eye movement (non-REM) Stage II, 233 +/- 13.8 in slow-wave sleep, and 233 +/- 40.0 in REM sleep versus 100 +/- 17.3 in wakefulness, p < 0.001). In contrast, there was no statistical difference in EMGdi in S between awake and any non-REM sleep stage (mean +/- SD, 100 +/- 20.5% in wakefulness versus 103 +/- 16.9 in non-REM Stage II and 100 +/- 14.8 in slow wave sleep; NS). However, EMGdi in REM sleep in S was statistically greater (132 +/- 28.3%) than that during wakefulness or any other sleep stage in space (p < 0.001). Therefore, gravity may play a much more significant role in the normal healthy human in the increased upper airway resistance during sleep than the relative atonia of the upper airway muscles. PMID- 8368632 TI - Sleep apnea and cardiac arrhythmias. Is there a relationship? AB - To determine if there was a relationship between cardiac arrhythmias and sleep apnea, we studied the prevalence of arrhythmias in a consecutive series of patients referred to our clinic for assessment of this disorder. Two hundred of 263 physician-referred patients were eligible for the study and, of these, 173 (86.5%) had complete investigations. All patients underwent a full night of polysomnography and Holter monitoring. Sleep apnea was diagnosed if patients had more than 10 apneas and hypopneas per hour (AHI). In 76 patients (43.9%) sleep apnea was diagnosed (median AHI = 33). The prevalence of arrhythmias in patients with sleep apnea versus those without was, respectively: complex ventricular ectopy (including ventricular tachycardia), 1.3% (95% CI, 0.4 to 6.9) versus 4.1% (CI, 1.6 to 10.1); frequent ventricular premature beats (> 30/h), 2.6% (CI, 0.8 to 8.9) versus 6.2% (CI, 2.9 to 12.8); second-degree atrioventricular block, 1.3% (CI, 0.4 to 6.9) versus 4.1% (CI, 1.6 to 10.1); sinus arrest, 5.2% (CI, 2.2 to 12.6) versus 1.0% (CI, 0.2 to 5.6). None of these differences was statistically significant. We conclude that the prevalence of cardiac arrhythmias is low in patients without serious cardiac or respiratory comorbidity who are referred for assessment of sleep apnea. Furthermore, the presence or absence of arrhythmias in this group is unrelated to sleep apnea severity. PMID- 8368633 TI - Comparison of gas exchange, lactate, and lactic acidosis thresholds in patients with chronic obstructive pulmonary disease. AB - During an incremental exercise test, three consequences of the onset of anaerobic metabolism can be observed: rise in blood lactate (lactate threshold, LT); fall in standard bicarbonate (lactic acidosis threshold, LAT); nonlinear increase in CO2 output (V-slope gas exchange threshold, GET). We compared these thresholds in 31 patients with COPD. We found that the GET and LAT overestimated the LT. A better relationship was found between LAT and GET, even though GET was significantly higher than LAT (by 124 ml/min; p < 0.0001). However, since the bias is appreciably greater at lower LAT values (likely because VCO2 kinetics are slower than VO2 kinetics), we separated the studies into two groups: (A) tests where LAT occurred within the first 2 min of the increasing work rate period, and (B) tests where LAT occurred after 2 min. For Group A, there was a substantial bias between LAT and GET (323 ml/min, p < 0.0001), whereas the bias was much smaller (only 5.4%, though statistically significant) for Group B (57 ml/min, p < 0.01). We conclude that when lactic acidosis occurs after the first 2 min of incremental exercise, the GET closely approximates the point at which blood bicarbonate begins to fall. PMID- 8368634 TI - KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. AB - KL-6, a mucin-like high-molecular-weight glycoprotein, is a serum marker indicating the disease activity of pneumonitis, such as idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and sarcoidosis. Immunohistochemical studies have shown that KL-6 is strongly expressed on Type 2 pneumocytes and also exists on epithelial cells in other organs. It has not been clarified whether the increased levels of KL-6 in sera from patients with pneumonitis are derived from the lower respiratory tract. In this study, KL-6 levels were evaluated in bronchoalveolar lavage fluid (BALF) samples from 9 healthy control subjects and 32 patients with interstitial pneumonitis. An abnormally high level of KL-6 in BALF was observed in 70% (7 of 10) of patients with IPF, 64% (9 of 14) of patients with sarcoidosis, and 100% (8 of 8) of patients with hypersensitivity pneumonitis but in none of the healthy control subjects. KL-6 levels in BALF were significantly correlated with numbers of total cells (p < 0.001), lymphocytes (p < 0.001), and neutrophils (p < 0.05) and with concentrations of albumin (p < 0.001) and total protein (p < 0.001) in BALF and, further, with serum KL-6 levels (p < 0.01). These results indicate that increased levels of serum KL-6 in patients with pneumonitis reflect the production levels of KL-6 derived from damaged or regenerating Type 2 pneumocytes in the lower respiratory tract. PMID- 8368635 TI - Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis. AB - Tuberculous meningitis is a very serious form of tuberculosis. In the absence of randomized controlled trials of alternative treatment regimens, its management depends on employing potent drugs that penetrate well into the cerebrospinal fluid (CSF). The penetration of isoniazid, rifampin, and streptomycin into the CSF of 27 Chinese patients was studied using fluorimetric and microbiologic procedures. Isoniazid rapidly diffused into the CSF, peak concentrations in excess of 3 mg/L, or over 30 times its minimal inhibitory concentration (MIC) against Mycobacterium tuberculosis being attained within 4 hr. In contrast, rifampin and streptomycin penetrated very slowly across the meninges, and CSF levels only slightly in excess of their MICs against M. tuberculosis were achieved. The penetration of the drugs into the CSF correlated poorly with differences in their partitioning between octanol/water and cyclohexane/water but could be predicted using a simple model based on their renal clearance rates and plasma protein binding. It is recommended that patients with tuberculous meningitis should be treated for at least 9 months with a combination of isoniazid, rifampin, and pyrazinamide, which may be supplemented in the first 2 mo with streptomycin. PMID- 8368636 TI - Evaluation of the protective efficacy of the killed Coccidioides immitis spherule vaccine in humans. The Valley Fever Vaccine Study Group. AB - A vaccine consisting of formaldehyde-killed spherules of Coccidioides immitis, previously shown to provide protection against development of lethal coccidioidomycosis in laboratory animals, was evaluated in humans. This double blind "Phase 3" study, conducted during the period 1980 to 1985, involved 2,867 healthy subjects with no history of coccidioidomycosis and negative skin tests. Randomized into vaccine (n = 1,436) or placebo (n = 1,431) groups, the former received three intramuscular injections of 1.75 mg (dry weight) of spherules, the latter received three injections of sterile 0.85% NaCl solution. Compatible clinical presentation with cultural or serologic findings permitted detection of coccidioidomycosis. Of those receiving vaccine, nine developed coccidioidomycosis and nine additional were suspected of having the disease. Of the group receiving placebo, 12 developed coccidioidomycosis, and 13 additional were suspected of having the disease. All cases and suspected cases were mild. Under the conditions of this study, a slight but statistically insignificant reduction in the incidence of coccidioidomycosis was noted in the vaccinated group compared with that in the placebo group, and there was no discernible difference in severity of disease between these groups. PMID- 8368637 TI - Early pulmonary physiologic abnormalities in beryllium disease. AB - By using the beryllium-specific blood lymphocyte transformation test (BeLT) as a screening tool, it is possible to identify beryllium disease before clinical symptoms or radiographic abnormalities develop. Little is known about the early pulmonary physiologic abnormalities in granulomatous lung diseases. We compared two groups: (1) "surveillance-identified" early beryllium disease patients, detected using the blood BeLT in workplace screening projects (n = 21), and (2) "clinically identified" beryllium disease patients who presented with symptoms or radiographic abnormalities (n = 15). We measured spirometry, lung volumes, diffusing capacity for carbon monoxide, arterial blood gases, and maximal exercise capacity. Physiologic abnormalities occurred in 12 of 21 (57%) surveillance-identified patients. The most common derangement was a rise in the dead space to tidal volume ratio (VD/VT) during exercise, suggesting a pulmonary vascular abnormality. None of the surveillance-identified patients had pure restriction, and only one of 21 had an abnormal diffusing capacity. In comparison, 93% of clinically identified beryllium disease patients had one or more abnormalities, the most sensitive indicator being the exercise capacity. One third had airflow limitation. Resting arterial blood gas analysis was abnormal in seven of 15 (47%), whereas diffusing capacity was low in only five of 15 (33%). Clinically identified patients performed less work, had more severe gas exchange abnormalities, and had higher VD/VT at maximal exercise than did surveillance identified patients. We conclude that alterations in gas exchange and the pulmonary vascular bed occur early in beryllium disease. PMID- 8368638 TI - Predictors of asthma and wheezing in adults. Grain farming, sex, and smoking. AB - We investigated predictors for asthma and wheeze in 1,634 men and women in the age group 20 to 65 yr from the town of Humboldt, Saskatchewan. On the basis of questionnaire responses, subjects were classified into mutually exclusive groups as asthmatic (n = 62), wheezing (n = 444), asymptomatic (n = 908), and symptomatic (n = 220) groups. After excluding the symptomatic group, we used polytomous logistic regression models to determine predictors of asthma and wheezing. Significant predictors for asthma were grain farming (odds ratio [OR] = 1.9, 95% confidence interval [Cl]: 1.1-3.5; p = 0.03) and sex (OR = 1.9, Cl: 1.1 3.2; p = 0.03; males compared with females). Significant predictors for wheezing were smoking (former smoker: OR = 1.8, Cl: 1.3-2.5, p < 0.001; current smoker: OR = 5.0, Cl: 3.8-6.7, p < 0.001; in comparison to nonsmoker) and grain farming (OR = 1.7, Cl: 1.3-2.4, p < 0.001). Age, level of education, and physical activity at work were not significant predictors for asthma or wheezing. None of the interaction effects between the predictors was significant. When stratified by sex, grain farming was a significant predictor of asthma in men but not in women. Nevertheless, smoking and grain farming were significant predictors of wheezing in both men and women. Our study raises the possibility that grain farming might be a risk factor for asthma and asthma-like symptoms. PMID- 8368639 TI - Asthma risk and occupation as a respiratory therapist. AB - In the modern hospital environment, many health care workers are exposed to hazardous substances. Among these hazards are respiratory sensitizers, irritants, and infectious agents. A previous cross-sectional study of Rhode Island respiratory therapists reported an excess risk of asthma after entry into that profession. Before the results of that study were published, we conducted a confirmatory mailed questionnaire survey of 2,086 Massachusetts respiratory therapists and 2,030 physical therapists and physical therapy assistants. Neither the survey questionnaire nor the accompanying cover letter revealed the focus of our investigation. A history of physician-diagnosed asthma was reported by 16% of respiratory therapists and 8% of control subjects. When analysis was restricted to those who developed asthma after entry into their profession, respiratory therapists still had a significant excess, 7.4 versus 2.8%. The odds ratio for respiratory therapy was 2.5 (95% Cl, 1.6 to 3.3) after adjustment for age, family history, atopic history, smoking, and gender. These results confirm the previous report of excess risk of asthma among respiratory therapists. This excess risk develops after entry into the profession and does not appear to be explained by bias or confounding. Efforts should be directed to identifying potential agents responsible for this form of occupational asthma. PMID- 8368640 TI - Performance of an asthma quality of life questionnaire in an outpatient setting. AB - The objectives of this study were to assess the validity, reliability, and responsiveness of a disease-specific quality of life questionnaire (AQLQ) in asthma patients presenting for assessment and treatment in an emergency department (ED). Fifty-two patients 18 to 64 yrs of age were surveyed in three EDs. Admitted and discharged patients with stable and unstable asthma were included. Patients were interviewed prior to discharge from the ED. They completed a self-report asthma questionnaire, the self-administered Sickness Impact Profile (SIP) and AQLQ, a global assessment of asthma severity, a symptom questionnaire, and pulmonary function testing. Forty-three (83%) patients were available for follow-up at 7 to 10 days, and they completed a similar series of tests. Moderate correlations were found between total SIP and AQLQ measurements (r = 0.49; p < 0.001). Correlations were high between physical domain scores of the SIP and AQLQ symptoms (r = 0.58; p < 0.0001) and activity limitations (r = 0.50; p < 0.0001). Low correlations were found between pulmonary function results and AQLQ domains, except activity limitations (r = 0.44; p < 0.001). High correlations were found between symptoms or global assessments and AQLQ (r > 0.6; p < 0.0001). The instrument is highly responsive to small changes in patient status and outperforms pulmonary function tests and symptom scores in this setting. Test-retest reliability in patients who were stable was substantial (intraclass correlation coefficients > 0.9) on all aspects of the AQLQ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368641 TI - Effect of leukotriene D4 and platelet-activating factor on human alveolar macrophage eicosanoid and PAF synthesis. AB - Leukotrienes (LT) and platelet-activating factor (PAF) can increase nonspecific airway reactivity in normal subjects, and they have been proposed as putative mediators of asthma. Alveolar macrophages (AM), which have receptors for and synthesize leukotrienes and PAF, also may play a role in the pathogenesis of asthma. The present study was designed to determine the effects LTD4 and PAF have on bronchoalveolar lavage (BAL) fluid and cells, including AM eicosanoid and PAF synthesis, and to relate them to changes in nonspecific airway reactivity. Airway reactivity to methacholine was measured in healthy, male volunteers at least 2 days before and 6 h, 1, 3, and 7 days after inhaling either LTD4 or PAF. At least 3 wk later subjects inhaled in random order either methacholine or the mediator to which they were previously exposed, and BAL was performed the next day. This sequence was repeated with the other chemical 3 wk or more later. LTD4 inhalation increased airway reactivity and stimulated AM thromboxane synthesis while it reduced stimulated AM LTB4 synthesis. LTD4 did not affect the number of percentage of BAL cells or the BAL fluid protein and histamine concentrations. PAF inhalation increased airway reactivity and the proportion of neutrophils and eosinophils recovered by BAL, but it did not alter AM eicosanoid and PAF synthesis or the BAL fluid protein and histamine concentrations. A relationship was identified between the PAF-induced increase in airway reactivity and the percentage of BAL neutrophils, but no correlation was found between LTD4- or PAF induced changes in airway reactivity and stimulated AM eicosanoid or PAF synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368642 TI - Allergen-induced biphasic plasma exudation responses in guinea pig large airways. AB - In this study involving sensitized guinea pigs (anesthetized intramuscularly with a 3:2 mixture of ketamine+xylazine, 1 ml/kg), we applied allergen (ovalbumin) selectively to the tracheobronchial mucosa (sparing the nasal passages and the terminal airways) and examined the occurrence of immediate and late-phase inflammatory exudation of plasma and plasma-derived mediators (bradykinins) into the airway lumen. The experiments were terminated 10 to 480 min after challenge. A selective lavage that sampled the surface liquids of the extrapulmonary bronchi and the lower trachea was performed. The amount of plasma (microliter) was determined by analysis of a plasma tracer, [125I]albumin, in lavage fluid and blood (plasma) samples. Ovalbumin, 3 to 12 pmol, and histamine, 5 and 10 nmol, produced a dose-dependent immediate exudation response (p < 0.001). The effects were nonneurogenic because they were not affected by topical lidocaine given in a dose (3 nmol) that prevented the exudative effect of capsaicin. The 6- and 12 pmol doses of ovalbumin (but not 3 pmol) produced a significant late-phase exudative response at 5 h (p < 0.001), and both the immediate and late phases were associated with increased (p < 0.01 to p < 0.001) levels of bradykinin in the lavage fluids. Histamine, even in doses that produced a greater early response than the allergen, did not produce a late-phase response. A single topical dose of an antiasthma steroid (budesonide, 12 mumol/kg) administered just before ovalbumin (6 pmol) had little effect on the immediate response but inhibited the late-phase response (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368643 TI - Effect of Hoe 140 on bradykinin-induced bronchoconstriction in anesthetized guinea pigs. AB - We have investigated the efficacy of the novel, highly potent, and stable B2 bradykinin (BK) antagonist Hoe 140 against BK-induced bronchoconstriction in guinea pigs via whole body plethysmography and compared different routes of administration. Our results clearly demonstrate that Hoe 140 is highly potent at inhibiting bronchoconstriction induced by either intravenous (i.v.) or inhaled BK. Intravenous BK was strongly inhibited by i.v. Hoe 140 (ID50 13.4 pmol/kg), and less by aerosolized Hoe 140 (ID50 1.34 nmol/kg). Aerosolized BK (235 nmol/kg) was strongly inhibited by 0.1 nmol/kg of aerosolized Hoe 140 given 30 min before. Hoe 140 is the first BK antagonist to effectively inhibit the bronchoconstrictor effect of aerosolized BK. The equieffective i.v. dose of Hoe 140, however, as about 100-fold higher. From the discrepancy in efficacy of Hoe 140 against i.v. and aerosolized BK, it was concluded that i.v. BK has no direct effect on the lung, in contrast to inhaled BK. Moreover, the high potency of Hoe 140 in the guinea pig lung does not confirm the hypothesis of a B3 BK receptor. Based on its high potency and good tolerability, Hoe 140 is appropriate to evaluate the role of BK in human airway diseases. PMID- 8368644 TI - Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? AB - To determine the histologic differences in the airways of patients who died from sudden-onset asthma and the more common slow-onset asthma, we studied seven cases of fatal asthma. The numbers of eosinophils and neutrophils, as well as extracellular deposition of their respective granule contents in the airway mucosa and submucosa, were determined and statistically analyzed. Four of the seven patients had slow-onset asthma attacks in which the time interval between onset of asthma and death was more than 2.5 h. In contrast, three patients had sudden-onset asthma in which the time interval between onset of asthma attack and death was less than 1 h. The four patients with slow-onset fatal asthma had more eosinophils (34.1 +/- 6.3 in slow-onset; 9.7 +/- 3.5 in sudden-onset; p = 0.002) and fewer neutrophils (4.8 +/- 2.0 in slow-onset; 16.8 +/- 5.4 in sudden-onset; p = 0.008) in the airway submucosa than did patients with sudden-onset fatal asthma. In addition, within the slow-onset fatal asthma group, eosinophils exceeded neutrophils in the airway submucosa (eosinophils > neutrophils, p = 0.002). By contrast, within the sudden-onset fatal asthma group, neutrophils exceeded eosinophils (neutrophils > eosinophils, p = 0.04). We suggest that sudden-onset fatal asthma is immunohistologically distinct from slow-onset fatal asthma and that it is characterized by a relative paucity of eosinophils in the face of an excess of neutrophils in the airway submucosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368645 TI - Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study. AB - In order to study whether hyperplasia or hypertrophy of cells is responsible for the thickening of airway muscles, 3-D morphometry of airway muscle cells was performed on resin-embedded semithin serial sections of autopsied lungs from 10 asthmatics and five control subjects. There were five Type I and five Type II asthmatic lungs, as defined in an earlier study, thickened muscles being found only in the central bronchi in Type I and distributed over the whole airway tree in Type II. The analysis was based on "unbiased" 3-D morphometry to obtain the numerical density NV of muscle cells using a "disector," a spatial probe introduced by Sterio in 1984, which we modified into a stack of serial sections. The mean number NL of cells per unit airway length and the mean volume Vc of a single muscle cell were also determined. In Type I asthmatics, the number of cells increased in the larger bronchi unaccompanied by cellular hypertrophy at any level of the airway tree. In contrast, in Type II asthmatics, hypertrophy was shown to prevail over the whole airway, but it was most remarkable in the bronchioles, whereas hyperplasia was mild and localized only in the bronchi. The two types of asthmatic lungs may therefore result from different pathogeneses. PMID- 8368646 TI - Nitric oxide synthesis inhibitors induce airway hyperresponsiveness in the guinea pig in vivo and in vitro. Role of the epithelium. AB - The administration by aerosol of the nitric oxide (NO) synthesis inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) or Ng-monomethyl-L-arginine (L NMMA), to spontaneously breathing anesthetized guinea pigs resulted in a significant enhancement of lung resistance (RL) after increasing intravenous doses of histamine. The maximal response was increased (p < 0.01) by 126% (L NAME) and 282% (L-NMMA) compared with the control groups. This effect was inhibited by giving an aerosol of the NO precursor L-arginine (L-Arg) but not by its inactive enantiomer D-arginine (D-Arg). Perfusion through the lumen of guinea pig tracheal tubes in vitro with nitric oxide synthesis inhibitors (120 microM) resulted in a significant increase in basal tone, suggesting a role for NO in the maintenance of basal tone. In addition, the histamine concentration-response curve was significantly shifted upward: the maximal response was increased (p < 0.01) by 335% (L-NAME) and 250% (L-NMMA) compared with the control group. This effect was concentration dependently inhibited by coincubation with L-Arg (120, 200, and 400 microM), but not with D-Arg (200 microM). Furthermore, removal of the epithelium resulted in an upward shift in the histamine concentration response curve: the maximal response was increased by 185%. However, incubation with L-NAME did not further increase tracheal responsiveness to histamine, but addition of L-Arg (360 microM), when a plateau was reached, relaxed the tissues to control values. Nitric oxide synthesis inhibition did not change the responsiveness of intact tissues in vitro after intraluminal stimulation with leukotriene D4, serotonin, or the cholinergic agonist arecoline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368647 TI - Effect on single-breath washout and lung function of elastase-induced emphysema in rats. AB - Lung volumes, diffusing capacity (DLCO), quasi-static pressure-volume curves (P V), forced expiration (FE) and He-SF6 single-breath washout (SBW) were performed in Wistar rats with emphysema induced by different doses of pancreatic elastase in saline, instilled intratracheally 6 wk prior to the tests. Emphysema was quantitatively assessed by mean linear intercept (Lm) measurements on 5-microns lung sections. Lung volume, P-V curve, and FE dependence on Lm, as well as the nonsignificant dependence of DLCO on Lm, are generally similar to results reported by others. The most interesting observation concerns the SBW: N2 slopes of the alveolar plateau, compared for identical lung volumes, did not change with the degree of emphysema. By contrast, the He-SF6 slope difference did depend significantly on the degree of emphysema. Based on the diffusion front theory, the present work suggests that in rats with elastase-induced emphysema, the phase III slope modifications relate mainly to elastic and not to structural alterations. PMID- 8368648 TI - Changes in the structure and mechanical properties of pulmonary arteries of rats exposed to cigarette smoke. AB - The effect of cigarette smoke on the structure and mechanical properties of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times per day with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The volume fractions of the cells, including smooth muscle cells and fibroblasts, and extracellular matrix components, including collagen, elastin, and remainder (components not specified in this study), of the pulmonary arteries of approximately 450 microns in external diameter (at zero pressure) were determined in smoke-exposed and control rats by using an electron microscopic method. It was found that the volume fractions of the fibroblasts, the collagenous bundles, and the elastic laminae of the pulmonary arteries were increased significantly, whereas those of the smooth muscle cells and the remainder were decreased significantly in both the 2- and 3-month smoke-exposed rats in comparison with those of the corresponding control rats. The mechanical properties of the pulmonary arteries were determined based on the in vitro dimensional measurement of the vessels at various inflation pressures and zero stress state. An increase in the stiffness of the pulmonary arteries was found in both the 2- and 3-month smoke-exposed rats. We conclude that cigarette smoke can induce structural and mechanical remodeling in the pulmonary arteries of rats. PMID- 8368649 TI - Detection of nonvolatile macromolecules in breath. A possible diagnostic tool? AB - The analysis of parameters in bronchoalveolar extracellular lining secretions has come into greater use in the diagnosis of diseases of the lung and respiratory passages. The bronchoalveolar lavage (BAL) method is thus used for sampling alveolar fluids or bronchial secretions. However, this method is invasive and therefore cannot be routinely employed for probe sampling. Based on the hypothesis that aerosol particles excreted in human breath reflect the composition of the bronchoalveolar extracellular lining fluid, experiments were performed to concentrate and analyze these aerosols directly using a noninvasive technique. Human exhaled air was directed through a set of cool traps and the condensate of 200 to 400 exhalations examined for nonvolatile components, such as proteins. In experiments conducted with volunteers, the amount of proteins in the breath condensate of 8 healthy individuals (of a total of 10) amounted to between 4 micrograms and 1.4 mg. The proteins were separated by two-dimensional polyacrylamide gel electrophoresis (PAGE) and compared to saliva samples of the respective volunteers. The results suggest that the proteins detected in breath originate partially from the naso-oropharyngeal tract and partially from lower regions of the airways. In clinical tests, the exhaled air of 13 patients suffering from various diseases of the respiratory tract was sampled and analyzed by immunoassays for inflammation parameters, such as interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptor protein, light chain (sIL-2R), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). In these tests, up to 370 pg IL-1 beta, 120 pg TNF-alpha, and 2,159 U sIL-2R per ml were measured in the breath condensate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368650 TI - Comparison of ventilatory support with intratracheal perfluorocarbon administration and conventional mechanical ventilation in animals with acute respiratory failure. AB - We investigated the efficacy of intratracheal perfluorocarbon (PFC) administration combined with mechanical ventilation to support gas exchange in adult animals with acute respiratory failure. These were compared with a similar group of animals treated with continuous positive-pressure ventilation (CPPV) with respect to respiratory parameters and postmortem lung histology. After lung lavage with saline, 18 adult rabbits were divided into three groups (n = 6 per group). All groups received conventional CPPV. Additionally, one group received intratracheal PFC administration at a volume of 18 ml/kg (corresponding to functional residual capacity) (PFC group); another received 18 ml/kg of saline administration (saline group), and the last had no further treatment (CPPV group). All groups were ventilated for 3 h using 100% oxygen, with the same ventilator settings of tidal volume of 12 ml/kg, respiratory frequency of 30/min, and positive end-expiratory pressure of 6 cm H2O. In the PFC group, PaO2 increased from 67.2 +/- 11.4 to 424.2 +/- 14 mm Hg and remained stable for 3 h with well-preserved PaCO2 values. Only in the PFC group were significant decreases in airway pressures and increase in respiratory system compliance seen. In the CPPV group, PaO2 stayed around 60 mm Hg and PaCO2 gradually increased. PFC treatment with conventional mechanical ventilation in acute respiratory failure proved to be a successful supportive technique to improve gas exchange at low inflation pressures. PMID- 8368651 TI - The immunoevasive activities of Pseudomonas aeruginosa. Relevance for cystic fibrosis. PMID- 8368652 TI - The lack of distensibility of asthmatic airways. AB - Asthma is characterized by chronic endobronchial inflammation and the deposition of collagen below the epithelial basement membrane. The functional significance of collagen deposition is unknown, but it can lead to loss of airway distensibility and hence to eventual loss of bronchodilator response. In this study we examined the volume of airway dead space by a single-breath, nitrogen plateau method at a range of lung volumes during inspiration. Participants were 10 asthmatics and 10 control subjects who were matched for lung volumes and age. The asthmatics increased their dead space by 27.0 ml/L compared with 37.3 ml/L in the control subjects (p = 0.014). The dead-space volumes at 50% TLC were no different (29.3 ml/L lung volume in asthma versus 26.9 ml/L in control subjects, p = 0.25). Loss of airway distensibility did not correlate, however, with loss of bronchodilator responsiveness, implying that factors other than mechanical airway distensibility may act to determine pharmacologic reversibility of airflow obstruction. PMID- 8368653 TI - Allergic bronchopulmonary mycosis caused by Pseudallescheria boydii. AB - Two cases of allergic bronchopulmonary pseudallescheriosis (ABPP) are described. These are the first cases of this allergic bronchopulmonary mycosis (ABPM) reported in which the clinical and serologic criteria are described. The first case was in a patient with mild asthma, and it resolved spontaneously after expectoration of a mucous plug. The second was in a patient with recurrent allergic bronchopulmonary aspergillosis with an exacerbation of ABPM caused by Pseudallescheria boydii. The total serum IgE, IgG, and IgE antibodies against P. boydii and the clinical picture well define ABPP. This diagnosis may be important to recognize in order to prevent a progression of the patient's lung disease. PMID- 8368654 TI - Management of complicated parapneumonic effusions. PMID- 8368655 TI - Evolution of therapy for childhood asthma. PMID- 8368656 TI - Estimating maximum ventilation: inclusion of maximum inspiratory and expiratory airflow variables. PMID- 8368657 TI - Increased lower airways responsiveness associated with sinusitis in a rabbit model. PMID- 8368658 TI - Neither emphysema nor Johnson's. PMID- 8368659 TI - Avoiding complications of long-term venous access. AB - Indwelling venous catheters are invaluable for long-term chemotherapy, antibiotics, and hyperalimentation. However, their placement and chronic use can cause serious complications. This study was done to develop guidelines for minimizing complications of long-term vascular access. Complications associated with 355 lines placed in 297 patients were recorded prospectively at the George Washington University Hospital. Single or double lumen catheters were placed via the infraclavicular subclavian approach (126), external jugular cutdown (133), internal jugular cutdown (22), and cephalic vein cutdown (42). While catheters were malpositioned in 15 cases (5.2%), route of placement did not influence this adverse outcome. Pneumothorax occurred only in the subclavian approach (5.6%). Axillary vein thrombosis was significantly more prevalent in catheters placed via the subclavian vein (10.3%) compared with the external jugular (2.3%) P < 0.05 or cephalic (2.3%) vein. Line sepsis occurred in 28 instances; this was statistically associated with an abnormal white blood count and with the use of double-lumen catheters (double-lumen catheter sepsis = 18.4%, single lumen = 4.4%, P < 0.01). The morbidity of long-term venous catheters is affected significantly by the route of placement, the number of catheter lumens, and the pre-placement white blood count. As a result of our analysis, we recommend single lumen catheter placement using the external jugular cutdown route whenever possible. PMID- 8368660 TI - Selective monitoring in abdominal aortic surgery. AB - Monitoring via a pulmonary artery catheter has been advocated for all patients undergoing abdominal aortic surgery. This study was performed to identify a subgroup of patients who could be safely monitored with a central venous catheter. One hundred twenty-eight consecutive patients undergoing elective infrarenal abdominal aortic surgery were prospectively evaluated for risk of developing perioperative myocardial dysfunction based on criteria determined by the history and physical examination, chest radiography, and electrocardiography. Forty-five patients were identified as having no clinical evidence of coronary artery disease. These patients were then monitored perioperatively using a central venous catheter. All patients monitored via a central venous catheter underwent surgery for abdominal aortic aneurysmal disease (66.7%) or aortoiliac disease (33.3%) without intraoperative complications. There were 15 postoperative complications in 12 (26.7%) patients, comprised mainly of pulmonary (7) and gastrointestinal (3) complications. The cardiac-related morbidity was 4.4 per cent and consisted of congestive heart failure (1) and renal failure (1). No perioperative myocardial infarctions were detected. One (2.2%) postoperative death secondary to aspiration pneumonia occurred. The results of this data suggest that there exists a subgroup of patients undergoing elective infrarenal abdominal aortic surgery that can be monitored safely via a central venous catheter in the perioperative period. PMID- 8368661 TI - Vascular complications of the intra-aortic balloon pump: an analysis of 436 patients. AB - Although the intra-aortic balloon pump can be a lifesaving device, vascular complications are often associated with its use. Four hundred thirty-six patients underwent insertion of a balloon pump over a 14-year period. Indications for the balloon pump were intraoperative pump failure (42%), unstable angina (24%), preoperative prophylaxis (22%), preoperative shock (9%), and postoperative support (3%). Placement of the intra-aortic balloon pump was by percutaneous insertion in 66 per cent of patients, the remainder were placed by direct exposure of the vessel. Vascular complications occurred in 46 (10.6%) patients. Limb ischemia was seen in 40 of 46 of these patients. Other complications included bleeding in three patients, dissection in two patients, and infection in one patient. The effects on morbidity of sex, diabetes, site of cardiac catheterization, duration of counterpulsation, and the presence or absence of pulses on admission were determined. Only the absence of pedal pulses on admission correlated with an increased incidence of vascular complications (P = 0.04). Twenty four per cent of those with complications were diabetics, compared with 16 per cent of patients who received balloon pumps but had no complications. Surgical interventions in the ischemic limbs consisted of thrombectomy alone (28 of 40) or thrombectomy and vascular bypass (5 of 40). Four femorofemoral crossover grafts and one saphenous vein interposition graft were used. Five limbs were lost to amputation, or 1 per cent of the entire group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368662 TI - Percutaneously placed dual-lumen silicone catheters for long-term hemodialysis. AB - Dual-lumen Dacron-cuffed silicone hemodialysis catheters placed percutaneously under fluoroscopic control have been used by us in 200 patients since July 1986. A total of 246 catheters were placed in 4 years, of which 172 were for long-term hemodialysis in place of prosthetic tube bridge arteriovenous shunts. One-year catheter survival estimate by Kaplan-Meier life table was 57 per cent, and mean survival estimate was 16.3 months. There were a combined 76 patient years of catheter experience, with some catheters lasting as long as 2 1/2 years. Catheter thrombosis occurred in 92 catheters, but 83 per cent of cases responded to thrombolytic therapy. There were exit site infections with thirty-nine catheters, but 90 per cent resolved with antibiotic therapy. Twenty-two bacteremias occurred with 19 catheters, which resulted in 15 catheter removals. The remaining seven cases of bacteremia responded to antibiotic therapy without catheter removal. Subclavian vein or superior vena cava thrombosis has not been a problem. Silicone catheters are a practical alternative to prosthetic tube bridge arteriovenous shunts for long-term hemodialysis. PMID- 8368663 TI - Venous insufficiency: a late sequelae of four-compartment fasciotomy in the lower extremity? AB - Four-compartment fasciotomies used to relieve abnormally high compartment pressures necessitate interruption of the ensheathing fascial membrane. In the calf, this is considered an important component in maintaining a viable musculovenous pump and preventing venous hypertension, a leading cause of venous insufficiency. Through postoperative physical examination and photoplethysmography evaluation of 47 patients who underwent this procedure, no indication exists that division of the fascial component leads to calf pump dysfunction and chronic venous insufficiency. Of the patients studied, 92 per cent had unchanged musculovenous pump function upon photoplethysmography reevaluation at 19 weeks compared with the initial values recorded 6 weeks postoperatively; 6 per cent had improved venous flow, while only one of the 47 (2%) had venous recovery measurements consistent with diminished venous flow. PMID- 8368664 TI - Bradycardia following carotid endarterectomy. AB - This study was performed to determine whether bradycardia complicates the postoperative course of patients undergoing carotid endarterectomy (CEA). The records of 216 patients undergoing 233 CEAs over a 2-year period were reviewed. Patients were divided into two groups based on their lowest Surgical Intensive Care Unit (SICU) heart rate (HR). Those with HR < 60 were in the Bradycardic (BRADY) group and those with HR > or = 60 were in the Non-Bradycardic (NON-BRADY) group. One hundred and sixteen patients developed bradycardia, with a mean (+/- SEM) HR of 51.1 +/- 0.5, compared with 117 NON-BRADY patients with a mean HR of 70.6 +/- 0.9 (P < 0.0005). There were no significant differences between the groups in age, use of cardioactive drugs, SICU severity of illness, or length of SICU stay. The systolic blood pressure for BRADY patients averaged 144 +/- 2.2 on admission and 144 +/- 2.2 (P = NS) in the SICU, while that of NON-BRADY patients rose from 143 +/- 2.3 on admission to 156 +/- 2.5 (P = 0.001). Fifty-four patients receiving a second CEA had a SICU HR not significantly different from those patients undergoing a first CEA. Of 17 patients who underwent bilateral CEAs during the study period, SICU HRs averaged 65.1 +/- 3.7 after the first procedure and 64.7 +/- 3.6 after the second (P = NS). The authors conclude that bradycardia following CEA is a frequent but benign postoperative finding that does not affect outcome, cause significant hypotension, or prolong the SICU stay. PMID- 8368665 TI - Dysphagia lusoria: aberrant right subclavian artery with a Kommerell's diverticulum. AB - A retroesophageal right subclavian artery, the most common congenital aortic arch abnormality, is an unusual cause of dysphagia in adults. The embryologic abnormality of the aortic arch is involution of the fourth vascular arch, along with the right dorsal aorta, leaving the seventh intersegmental artery attached to the descending aorta. This persistent intersegmental artery assumes a retroesophageal position as it proceeds out of the thorax into the arm. Since compression of the esophagus by this right subclavian artery may produce dysphagia, the term "dysphagia lusoria" ("dysphagia by freak of nature"), has been used to describe the symptom complex. The presence of an aneurysm of the artery or Kommerell's diverticulum at its aortic origin is more likely to produce symptoms from esophageal compression. This case presents a middle aged adult with an associated Kommerell's diverticulum and dysphagia. Surgical correction was used to relieve his symptoms and to correct the diverticulum of the proximal right subclavian artery. The embryologic changes that occur are discussed in detail. PMID- 8368666 TI - Delayed pneumothorax after central venous access: a potential hazard. AB - Percutaneous central venous catheter access is common-place in surgical patients. Though several major complications of this procedure have been described, pneumothorax is the most common. Pneumothorax is routinely assessed by a chest X ray within 2 hours after catheter placement. During a recent 6-month interval, the authors identified five patients with delayed onset and diagnosis of pneumothorax following percutaneous central venous access. All immediate post insertion chest X-rays were normal; however, subsequent chest X-ray showed evidence of pneumothoraxes. The pneumothorax contributed to the death of one patient on positive pressure ventilation. A review of the literature revealed a total of 18 patients in the English literature with this complication. Although the incidence of delayed pneumothorax is low, it is, in some instances, life threatening, particularly in patients on positive pressure ventilation. A high index of suspicion is required to diagnosis and treat this reversible condition. PMID- 8368668 TI - The role of combined liver/kidney transplantation in end-stage hepato-renal disease. AB - The study describes the indications and results of combined liver/kidney transplantation in eight patients suffering from end-stage hepato-renal diseases. The causes of primary renal failure were hyperoxaluria type I (2/8), diabetic nephropathy (2/8), glomerulonephritis (2/8), congenital pyelonephritis (1/8), and polycystic kidneys (1/8). Only five of these patients were on chronic dialysis prior to transplantation. The indication for kidney transplantation in the other three patients was low GFR (< 20 mL/min) and the anticipation of further deterioration of the renal function after liver transplantation as a result of cyclosporine toxicity. The end-stage liver diseases were chronic active hepatitis (4/8) and alcoholic cirrhosis (2/8). There was no evidence for liver failure in two patients undergoing combined transplants for primary hyperoxaluria. The 1 year patient survival rate is 75 per cent, and at that time, kidney and liver function were found to be within normal range. In conclusion, excellent long-term patient survival, as well as kidney and liver graft function, can be achieved in patients suffering from complex end-stage disease of both organs who undergo combined liver and kidney transplantation. PMID- 8368667 TI - Arterial injuries of the thoracic outlet: a ten-year experience. AB - Arterial injuries of the thoracic outlet are complex and require a precise plan for adequate management and prompt exposure of injured vessels. Our 10-year experience with 28 such injuries is reviewed. Arteriography was performed whenever possible in stable patients (15) and aided in planning the operative approach. Unstable patients with active bleeding, pulsatile or expanding hematoma, or pulse deficit were taken to the operating room without delay. A thoracic approach was required in 15 patients, and the exposure was extrathoracic in 12 patients. Airway was secured with liberal use of emergency endotracheal intubation (16 patients). Primary repair was possible in 16 patients, with grafting performed in eight and ligation in three. One vertebral artery injury was successfully controlled with embolization. Venous injuries were repaired in six patients and ligation was necessary in eight; there was no significant morbidity. Two patients died in this series from complications of severe hemorrhage. Significant morbidity was encountered from associated neurologic injuries in 15 patients. Stroke was evident in two patients, both of whom were moribund preoperatively. Proximal subclavian artery injuries were particularly more problematic and frequently required an interim anterior thoracotomy for early control of exsanguinating hemorrhage. Our philosophy in the management of these injuries and choices of exposure are discussed in detail. PMID- 8368669 TI - Predicting the results and outcome of patients who undergo abdominal CT scanning while in the surgical intensive care unit. AB - Postlaparotomy patients who remain in the Surgical Intensive Care Unit (SICU) are frequently suspected of harboring an intra-abdominal abscess (IAA). Computed Tomography (CT) of the abdomen has been advanced as an accurate method to diagnose an IAA. To determine the clinical parameters predictive of CT scan results, and the survival of such patients, this study reviewed a consecutive series of 29 postlaparotomy patients who were evaluated by abdominal CT scan while in the SICU. An IAA was identified significantly more frequently by CT when patients were explored for a GI malignancy (70% vs 30%; P < 0.05) and when patients were operated upon electively (11.1% vs 20.0%; P < 0.05). Postoperatively, alert patients were significantly more likely to have a CT scan positive for an IAA than were patients who were lethargic or nonresponsive (90% vs 10%; P < 0.05). Laboratory data, including radiographic studies, were not predictive of the CT scan results. A negative CT scan modified therapy in only 10.5 per cent of patients, while a positive scan altered therapy in 70 per cent of patients (P < 0.05). The overall survival for this group was 48.1 per cent. The identification of an IAA by CT scan did not significantly improve survival (42% with an IAA vs 40% without an IAA). APACHY II scores were significantly increased in nonsurvivors (17.4 +/- 6.0 survivors vs 23.76 +/- 7.8 nonsurvivors; P < 0.05). Our data indicate that in critically ill postlaparotomy SICU patients who were evaluated by abdominal CT scanning, there are some clinical clues that tend to predict whether or not CT scanning will identify an IAA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368670 TI - Endoscopic applications in thoracic surgery: video-assisted thoracoscopic surgery. AB - Twenty-eight cases of video-assisted thoracoscopic surgery were performed in a 10 month period. Twenty-seven of the 28 cases were completed without a standard thoracotomy. In one of the 28 cases, inadequate visualization secondary to extensive adhesions necessitated conversion to thoracotomy. There were no complications secondary to the video-assisted thoracotomy or video malfunction. Video-assisted thoracoscopic surgery provides the thoracic surgeon with advantages not enjoyed with standard thoracotomy and thoracoscopic techniques. These advantages include: decreased patient pain and recovery time, increased latitude of movement for the surgeon, visualization by assistant and observers, adjustable magnification for close examination of pathology and still photo and video recording capabilities. PMID- 8368671 TI - Thru-knee amputation: the operation of choice for non-ambulatory patients. AB - Between 1983 and 1990, 32 consecutive patients had 35 thru-knee amputations for ischemia causing infection or gangrene of the lower leg. Twenty-seven patients were nonambulatory, five had limited mobility, and none were considered to be candidates for rehabilitation with a prosthesis after surgery. The average age was 73 years. Thirty-day hospital mortality was 3 per cent. The incidence of complications was low, and healing was achieved in 97 per cent of survivors. One patients required revision to an above-knee amputation. Average postoperative hospital stay was 8.7 days. It is concluded from this study that thru-knee amputation is the treatment of choice in patients with nonsalvageable ischemic legs and in whom ambulation is not planned after operation. PMID- 8368672 TI - Management of the difficult appendiceal stump: how I do it. AB - The appendix can usually be removed by the standard technique of stump ligation after transection, with or without inversion of the stump into the base of the cecum. When inflammation or necrosis extends into the cecum and the appendix cannot be ligated at its base, there are several options that can be employed. These include appendicocecostomy, partial cecal excision with a stapling instrument, and right colon resection. These techniques have been used 16 times in 249 patients operated upon for appendicitis. Although these techniques will be required infrequently, when they are necessary the risk of appendiceal stump breakdown with peritoneal soilage or cecal fistula can be minimized. PMID- 8368673 TI - Endoscopic placement of long intestinal tubes. AB - Partial intestinal obstruction has been successfully managed by the use of long intestinal tubes. For proper decompression, the long tube must pass beyond the pylorus; however, failure of the tube to progress by gravity alone has been reported to be as high as 46 per cent. A simple method of endoscopic placement of the long tube into the duodenum is described. If one is familiar with performing upper endoscopy, this technique can be learned easily. PMID- 8368674 TI - [Molecular advances in "non-mendelian" genetics. Implications for pediatrics]. PMID- 8368675 TI - [Sepsis caused by coagulase-negative Staphylococcus in the newborn infant. Clinical and therapeutic aspects]. AB - This study deals with sepsis caused by coagulase-negative stapylococci in a neonatal intensive care unit over a period of four years and eleven months. The global incidence was 20.7/1000 (50 cases out of a total of 2,416 admissions) and was higher in newborns with lower weight and with a shorter gestational age. The most significant clinical manifestations were fever, paleness, and apnea/bradycardia. In all cases the germ was sensitive to vancomycin. Evolution was favourable in all patients, in spite of the initial gravity of some cases. Sepsis due to coagulase-negative staphylococci is the most frequent cause of nosocomial infection in our environment. PMID- 8368676 TI - [Organochlorine compounds: correlation between maternal and infantile blood levels, maternal milk and maternal-infantile parameters. Study in the province of Huelva]. AB - In our study of the levels of organochlorine compounds (OCC), several factors were taken into account. In the mother, age, diet, place of residency, profession, the number of previous breast-fed children and alcohol and tobacco intake. We then studied the effect of the OCC passed through the placenta. Here, we checked the length of gestation, the birth weight, the cephalic perimeter measurement, the possible neurological alterations such as hypotonie and hyporreflexie and the possible clinical repercussions of the OCC. The OCC studied were, DDT, hexachlorobenzene (HCB), hexachlorocyclohexanes (HCH) and isomers alpha, beta and gamma or lindane, dieldrin, heptachloro epoxide (HE) and polychlorobiphenyl compounds (PCB). The samples studies included, blood for the mother and umbilical cord during the delivery, blood from the babies at the ages of one and three months, and the mother's milk (n = 30) and formula milk (n = 20) one and three months after birth. The analytical study was made at the National Institute o Toxicology in Seville with the following methods, gas chromatography, electron capture detector and mass spectrometry. The statistical analysis was based on the Kruskal-Wallis, Shapiro Wilks, Levene, Pooled and Separate tests. We have found that older mothers and those who consumed more fatty meat and blue fish had statistically significant higher levels of OCC. There were also differences depending on the place of residency. The newborn babies with a greater birth-weight and cephalic perimeter measurements also had higher levels of OCC. In these babies, we also found clinical symptoms such as hypotonie and hyporreflexie. PMID- 8368677 TI - [Immunity against tetanus in childhood]. AB - In order to evaluate the programs of vaccination against tetanus, we have studied the presence of specific antibodies in a sample of children and adolescents from our region. We used a passive hemagglutination test, corroborating the results by a biological assay based on toxin-neutralization. Among the subjects investigated, 93.2% (551/591) had neutralizing toxin-antibodies at a protective level (> or = 0.01 ui/ml). The younger children were more protected (97.5% in children from 1 to 5 years old, and 79.2% in children from 16 to 19 years of age), (X2 = 25.39, p = 0.000-). We did not find any significant differences between the sexes in the degree of protection. Among protected subjects, the higher antibody titers were observed in children from 6 to 10 years old, coinciding with the age of a booster vaccine. The results show an excellent immunization coverage among the childhood population in our region. They also confirm the high effectiveness of this vaccine. However, this high protection was not found among people above the adolescent period. PMID- 8368678 TI - [IgG subclasses: placental transfer in the full-term neonate and their evolution during the first 3 months of life]. AB - The authors studied the placental transfer of IgG subclasses in 43 newborns (NB) and their mothers. All the observations included low-risk pregnancies and full term deliveries. The values expressed in arithmetric mean +/- standard deviation (means +/- SD), and referred in mg %, showed the following results: maternal Ig Gtotal 1,183 +/- 237 versus (vs.) NBG 1,179 +/- 187; maternal Ig G1 792 +/- 230 vs. NB 822 +/- 124; maternal Ig G2 138 +/- 77 vs. NB 209 +/- 70; maternal Ig G3 48 +/- 33 vs. NB 95 +/- 30, and maternal Ig G4 10 +/- 8 vs. NB 4.9 +/- 2. The relation between the average levels of maternal and cord serum was 1, 1.5, 1.9 and 0.48 for Ig G1, Ig G2, Ig G3 and Ig G4, respectively. It was also proved a maximum decrease in the levels of the subclasses in the first three months for the Ig G3, a percentage being noticed in the third month, in relation to the NB level, of 18, 29, 1.9 and 19% for Ig G1, Ig G2, Ig G3 and Ig G4, respectively. After primovaccination, a response was produced and it affected the 4 subclasses: Ig G1 845 mg %, Ig G2 229 mg %, Ig G3 38 mg % and Ig G4 7.44 mg %, with an increment in relation to prevaccination values of 5.5, 3.7, 20.7 and 12.4, respectively. The authors concluded by showing reference patterns in the active placental transfer of Ig G subclasses in normal full-term newborns. PMID- 8368680 TI - [Prognostic value of the electroencephalogram in hypoxic ischemic encephalopathy]. AB - In order to check the prognostic implications of EEG tracings in hypoxic-ischemic encephalopathy (HIE), we carried out prospective EEG recordings in 116 newborn babies (65 term and 51 premature) admitted to our neonatal intensive care unit as a result of perinatal asphyxia. Forty term neonates were found to have critical and/or intercritical epileptiform EEG alterations; the developmental results of 23 of these cases (57.5%) were adverse and were favorable in 17 cases (42.5%). Given that unfavorable results occurred in only 4 of the other 25 term neonates, the epileptiform EEG alterations were statistically significant for adverse developmental results (p < 0.005). Of the premature neonates, 29 were found to have critical and/or intercritical epileptiform EEG alterations. The developmental results were adverse in 19 of these children (65.5%) and favorable in 10 cases (34.8%). The statistical evaluation in this case showed a barely significant difference (p < 0.005) between epileptiform EEG alterations and poor developmental outcome when uncorrected age was used, and no statistically significant difference when corrected age was used. Thus, we conclude that although epileptiform EEG anomalies may serve as markers for neurological development impairments, they must be considered in conjunction with the background EEG tracing. PMID- 8368681 TI - [Colloidal bismuth subcitrate and amoxicillin in the treatment of Helicobacter pylori infection in children]. AB - We have analyzed the effect of treatment with colloidal bismuth subcitrate (CBS) and amoxicillin in a series of 60 children (age range: 2.9-18 years) infected by Helicobacter pylori (HP). The following results were found: clinical remission 70%; endoscopic normalization 55%; histological normalization 61.6% and HP eradication 53.3%. The improvement of histological activity (100% vs 11.7%) and histological normalization (90.6% vs 28.5%) were significantly more frequent in the HP eradicated group as compared with the persistent HP group (p < 0.001). The present study suggests that combined therapy with CBS and amoxicillin is not the most adequate treatment to eradicate HP in children and supports the role played by HP in the development of antral histologic lesions. PMID- 8368679 TI - [Controlled clinical assay in Clonidine, arginine aspartate, alpha-ketoglutarate of Ornithine and Ciproheptadine as growth stimulants in children with short stature]. AB - Eighty-one healthy prepubertal children of short stature, between two and twelve years of age, were divided into four homogeneous groups. Each group was treated with a placebo for one year and for a second year with one of the following drugs (double blind): clonidine (CI), arginine asprate (AA), ornithine alphaketoglutare (OKG), or cyproheptadine (Cp). CI and OKG did not better the standard deviation of height. AA and Cp did, but to no greater extent than the placebo. The growth rate did not change in any group. The ratio of bone age/chronological age was significantly higher at the end of the OKG year than at the end of the year with placebo, a difference that was not found in any other group. The prognosis of adult height (TW2) did not change in any group. The standard deviation of weight increased in all groups, both with the placebo and the various drugs, without significant differences between the groups. The CI caused frequent clinical side effects, including a reversible increase in transaminases in one child. The Cp stimulated hunger. The AA and OKG did not produce side-effects and the placebo increased appetite in 11% of the children. Somatomedin C was significantly higher after one year with Cp than after one year with the placebo, significantly higher after the placebo than after CI and AA and there was no difference between the treatment with the placebo and OKG. Growth hormone values in a 24 hour urine sample were so scattered that we do not consider them helpful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368683 TI - [Cholelithiasis in children: apropos of 14 cases]. AB - Between 1980 and 1990, we have diagnosed fourteen cases of cholelithiasis in children at our hospital. Abdominal pain was the most common symptom. Diagnosis was made by abdominal ultrasonography in all of the cases. Risk factors were found in 4 children. Family history was present in four patients. The treatments performed included cholecystectomy in five cases, extracorporeal lithotripsy in one case and a dietary regimen with regular clinical reviews in eight patients. PMID- 8368682 TI - [Predisposition of Down syndrome to chronic infection with the hepatitis B virus]. AB - In order to know in Down's Syndrome (DS) the age of infection by hepatitis B virus (HBV), the incidence of evolution to a chronic carrier status and the optimal age for vaccination against this virus, a study of the prevalence of HBV markers was carried out in 302 mentally retarded children: Group I, 51 pre schoolchildren with DS (mean age 2.9 +/- 1.6 years); Group II, 72 schoolchildren with DS (mean age 13.8 +/- 3 years) and Group III, 179 schoolchildren with other types of mental retarded (OMR). Children from group II and III attended the same school as external day-pupils. Fifty eight percent of schoolchildren with SD presented at least one HBV-marker while this percentage was of 25% in schoolchildren with OMR (p > 0.05) or pre-schoolchildren with DS (p > 0.005); DS schoolchildren become also HBV chronic carrier with higher frequency than ORM schoolchildren (40 vs 17) (p > 0.05) and they maintained HBV replication in a higher proportion of cases (36 vs 4) (p > 0.05). In conclusion children with DS acquire easily HBV infection and this occurs when they attend the school independently that the school is a closed or an open institution. They also become more frequently HBV chronic carriers and they maintain HBV replication; so, they must be vaccinated before they begin to attend school and they must be treated with antiviral agents as soon as possible. PMID- 8368684 TI - [Atherogenic risk factors in children of parents with ischemic heart disease]. AB - We have studied serum lipid levels and dietetic intake in 38 children whose parents had ischemic heart disease (HPCI) before 55 years of age and in a control group (n = 114). In the HPCI group, 25% had serum levels of total cholesterol higher than 200 mg/dl; only 2 children presented elevated levels of LDL and apo B. Dietetic intakes in both groups were similar, with a high protein (16-17% of calories) and fat (39-42% of calories) intake and a low carbohydrate intake (40.46% of calories). In both groups the percentage of monounsaturated fat was higher than other types of fat. The most frequent phenotype in the HPCI group was IIa (8 children). Only 1 child showed a IIb phenotype. This finding may be due to the variability of this phenotype in the same individual throughout life. In the families (n = 8), we have detected 2 families with polygenic hypercholesterolemia (HP), 2 others with familial combined hyperlipidemia (HFC) and 4 without family history of hyperlipidemia. Taking into account the lipid profile in children of the HPCI group, we have detected the presence of familial dysliproproteinemias. It appears that dietetic intake is not an atherogenic risk factor in these patients. PMID- 8368685 TI - [Benign recurrent paralysis of the sixth cranial nerve in childhood]. PMID- 8368686 TI - [Acute megakaryoblastic leukemia in infancy]. PMID- 8368687 TI - [Pulmonary arteriovenous fistula. Clinical course during a 6-year follow-up]. PMID- 8368688 TI - [Benzodiazepine withdrawal syndrome in newborn infants. Clinical cases]. PMID- 8368689 TI - [Type I spinal muscular atrophy in twins]. PMID- 8368690 TI - [Is it necessary to remove all button-type batteries accidentally ingested by infants?]. PMID- 8368691 TI - [Breast feeding and the infant food industry: mutual respect as a form of collaboration]. PMID- 8368692 TI - [The 11q (-) syndrome. Report of a new case]. PMID- 8368693 TI - [Congenital absence of a lumbar pedicle]. PMID- 8368694 TI - [Accidental organochlorine insecticide poisoning]. PMID- 8368695 TI - [Rheumatic fever associated with Schoenlein-Henoch purpura]. PMID- 8368696 TI - The early days of the antinuclear antibody story: where and how did it all start? PMID- 8368697 TI - [Is the concept of somatization useful to the clinician?]. PMID- 8368698 TI - [Somatoform disorders. Analysis of 43 patients in an unit of internal medicine. Diagnostic attitude and proposal of management]. AB - The frequency of hospitalization for somatoform disorders in France has been difficult to evaluate owing to the lack of papers published on this subject. Retrospective analysis of the medical records of 43 patients hospitalized on an internal medicine ward for whom this diagnosis was retained enabled us to characterize this population according to the following criteria: socioeconomic professional group, family environment, probable triggering factors, and patient's evolution before and after hospitalization. Based on this study, we propose a diagnostic approach to and some guidelines for management of these patients, and discuss their place in internal medicine. PMID- 8368699 TI - [Acute attacks of hepatic porphyria: specific treatment with heme arginate]. AB - Severe hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are hereditary diseases. Each type of porphyria is the result of a specific decrease in the activity of one of the enzymes of heme biosynthesis. Acute attacks are very serious: the abdominal pains are severe and the neurological manifestations can lead to death or incomplete recovery with irreversible sequelae (usually paralysis). Since 1985, the prognosis of acute attacks has been greatly improved by the introduction of heme-arginate. The 69 acute attacks (30 patients, 4 men and 26 women) that we treated with heme arginate between 1988 and 1991 are described in this report. All patients were infused with 250 mg/d of heme-arginate for 4 days: the mean duration of abdominal pain was 2.5 days (SD 0.72). For 95 p. 100 of the attacks, the total hospitalization time was 5 days or less; side effects were very minor. In every case, a favorable response was dependent upon the early initiation of heme therapy. PMID- 8368700 TI - [Clinical study of 12 cases of malignant non-Hodgkin's lymphoma of the orbital region]. AB - Over an 8-year period in the Departments of Hematology, Ophthalmology and Internal Medicine of our hospital, 12 cases of orbital and adnexal malignant non Hodgkin's lymphoma were reported. Diagnostic elements varied, including local tumefaction, watering eyes, uveitis, and unexplained, long-term fever. Nine patients had primary paraocular lymphomas involving either orbital structures, the lacrimal gland or the eyeball, but after appropriate staging, the disease was found to be disseminated in 5; the 3 other cases were secondary orbital lymphomas. Intermediate or high grade histological types were predominant (9 patients) in our series. Radiation therapy, alone or combined (5 patients) with chemotherapy, was administered in 8 cases; other treatments consisted of chemotherapy (2 cases) or steroids (2 cases). Evolution was poor, with only 4 patients surviving at 34-180 months of follow-up. The main prognostic factors were tumor stage and histological grade. The clinical characteristics of this group are compared to those reported in the literature. PMID- 8368701 TI - What does the future hold for the ANCA? PMID- 8368702 TI - [Value of phenotyping by cytofluorometry in hematology and clinical immunopathology]. PMID- 8368703 TI - [Liposomes, in the treatment of infections]. PMID- 8368704 TI - [Familial benign hypercalcemia or familial hypocalciuric hypercalcemia]. PMID- 8368705 TI - [Temporal arteritis. Elements of differential diagnosis of Horton disease]. PMID- 8368706 TI - [Sudden death in an adult and detection of a cardiac site of sarcoidosis]. PMID- 8368707 TI - [Status epilepticus following voluntary poisoning with buflomedil]. PMID- 8368708 TI - [Multiple paraneoplastic syndromes (limbic encephalitis, peripheral neuropathy and Schnitzler's syndrome) in an association of Waldenstrom's macroglobulinemia and pulmonary epidermoid carcinoma]. PMID- 8368709 TI - [Bifocal spondylodiscitis simulating rhizomelic pseudo-polyarthritis]. PMID- 8368710 TI - [Bacterial ascites caused by Salmonella enterica subsp. enterica serotype Indiana]. PMID- 8368711 TI - [Herpetic esophagitis in immunocompetent patients]. PMID- 8368712 TI - [Visceral leishmaniasis with dysimmunitary manifestations and renal involvement]. PMID- 8368713 TI - [The Supreme Court for insulin?]. PMID- 8368714 TI - [The future of mortality: epidemiological centering]. PMID- 8368715 TI - [Cardiovascular risk factors in 4,215 subjects in the service and industrial sectors (the CESAME survey)]. AB - A prospective transversal study was undertaken by occupational health physicians on more than 4,000 individuals including almost 800 women working in the same company with the following aims: a) to compare the prevalence of a certain number of classically recognized cardiovascular risk factors in 2 types of populations, service versus manufacturing industries, in the Paris region; and b) to understand these populations better so as to develop educational and information campaigns specifically adapted to their needs. Several elements were recorded in a computer data bank during the physical examination: blood pressure, blood cholesterol, smoking history, blood triglycerides, blood sugar, the ratio of measured to theoretical weight and physical activity. For each of these parameters, a value above a determined threshold level was defined as a risk factor. For men working in service industries, the percentages of heavy smokers (24%), hypercholesterolemia (18%), and hyperglycemia (7%) were significantly higher than in the manufacturing sector (19.3, 15 and 2.4%, respectively). In manufacturing industries, the percentages of men with hypertension (15%), hypertriglyceridemia (10%), who were overweight (24%) or had a low high density lipoprotein level (10%) were significantly higher than in the service sector (3.1, 7.5, 20 or 8.2%, respectively). The percentage of women smoking more than 20 g of tobacco per day (25.5%) in the service sector was significantly higher than that in manufacturing industries (4.25%). In contrast, in the manufacturing sector, the percentages of hypertensive (6%) and obese (24%) women were significantly higher than those in the service industries (1.1 and 16%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368716 TI - [Treatment of hypereosinophilic syndromes of myeloproliferative expression with the combination of hydroxyurea and interferon alpha. Apropos of 7 cases]. AB - Seven patients suffering from hypereosinophilic syndrome with clinical and/or hematological symptoms of a myeloproliferative syndrome were treated with a combination of hydroxyurea and interferon-alpha. To date, 6 of them have been followed for more than 1 year. In all cases, this therapy decreased circulating hypereosinophilia to under 1,500/mm3 and obtained normal eosinophil levels in 5 patients with a parallel regression of visceral complications. None of the patients experienced treatment-associated side effects, particularly hematological ones. Hypereosinophilic syndrome has a poor prognosis due, for the most part, to the development of visceral, cardiac and neurological complications, and, more secondarily, to the risk of progression towards acute leukemia. Conventional treatments, corticosteroids and hydroxyurea, have greatly improved the prognosis, but failure of these therapeutics remains common in the myeloproliferative form of the disease. Because interferon-alpha was proven to effectively treat chronic myeloid leukemia, it has been proposed for the treatment of hypereosinophilic syndromes, and encouraging results have been obtained despite the high daily doses required to control the disease. In the future, its association with hydroxyurea could represent an alternative therapy capable of controlling the disease at low doses thereby limiting the risk of side effects. PMID- 8368717 TI - [Anatomo-clinical conference. Hopital Bichat-Claude Bernard. Case No. 2-1993. Recurrent subcutaneous and peritoneal abscesses]. PMID- 8368718 TI - Interview with Joaquim Coll. What is going to happen tomorrow as far as secondary Sjogren's syndrome is concerned?. Interview by P. Youinou. PMID- 8368719 TI - [Insulin resistance and arterial hypertension]. PMID- 8368720 TI - [Insulin, triglycerides and atheroma. Epidemiological data and hypotheses]. PMID- 8368721 TI - [Classification of dyslipoproteinemias of genetic origin]. PMID- 8368722 TI - [Presentation of results of a general review]. PMID- 8368723 TI - [Cogan's syndrome disclosed by meningitis. Corticoid therapy inducing rapid improvement in deafness]. PMID- 8368724 TI - [Pseudo-periodic disease with hyper IgD]. PMID- 8368725 TI - [Treatment of refractory causalgia with topical capsaicin]. PMID- 8368726 TI - [Longitudinal fatigue fracture of the tibia]. PMID- 8368727 TI - [Rheumatoid purpura in adults and mycoplasma infection]. PMID- 8368728 TI - [Hemophilus parainfluenzae: a cause of severe infectious endocarditis in the healthy heart]. PMID- 8368729 TI - [Pseudo-achalasia and cancer of the bladder]. PMID- 8368730 TI - Genes coding for antigens recognized on human tumors by autologous cytolytic T lymphocytes. PMID- 8368731 TI - Polyvalent melanoma vaccine improves survival of patients with metastatic melanoma. PMID- 8368732 TI - Active specific immunotherapy of human colorectal carcinoma with an autologous tumor cell/bacillus Calmette-Guerin vaccine. PMID- 8368733 TI - Treatment of human melanoma with a hapten-modified autologous vaccine. PMID- 8368734 TI - Active specific immunotherapy of melanoma with allogeneic cell lysates. Rationale, results, and possible mechanisms of action. AB - Since 1985, we have conducted clinical trials with a therapeutic melanoma vaccine (melanoma theraccine). Mechanical lysates of two melanoma cell lines chosen for their complementary characteristics were combined with the adjuvant DETOX and injected subcutaneously on weeks 1, 2, 3, 4, and 6 for one or two courses and then monthly in patients with objective clinical responses. Of 106 patients, 20 had objective clinical regression of tumor masses, 5 with complete responses. The median duration of response was 21 months. Twelve patients lived at least 2 years, with a median survival of nearly 3 years. Two of them are free of disease for > 2 and > 6 years, respectively. However, it was not necessary to achieve complete remissions to cause an increase in survival, and most of the long surviving patients have one or more (stable) residual nodules. The pace of the disease process was clearly slowed in those individuals. A rise in the level of cytotoxic T-lymphocyte precursors in the blood (pTC) correlated with clinical response. Only those patients who had a rise in pTC had a remission. In addition to "classical" CD8+ Tc, CD4+ Tc were cloned from the blood of immunized patients. Melanoma-specific Tc of both types that killed autologous melanoma but not matched lymphoblastoid cells were detected. Allogeneic melanoma cell lines were also killed, with mainly HLA-A2/28 and HLA-B12/44/45 degenerate restriction. CD4+ Tc were restricted by HLA Class I antigens, as judged by their killing of HLA Class II-negative melanomas and blocking by anti-class I antibodies. Other CD4+ clones were blocked by both anti-HLA Class I or anti-Class II MHC monoclonal antibodies, and only two were blocked only by anti-HLA Class II. Immunohistory revealed CD4+ and CD8+ T cells in lesions under rejection, but the predominant cells were macrophages, suggesting delayed-type hypersensitivity as a possible mechanism. Clinical responses were found most often in patients with HLA-A2/28, B12/44/45, and -C3, particularly when two or more of those alleles were present. This may have been due either to (1) similarity of MHC antigens between one of the immunizing melanomas and the patient's melanoma or (2) the intrinsic importance of these MHC molecules in presenting melanoma-associated antigens to Tc in vivo. IFN-alpha 2 b salvaged 8 of 18 patients who failed with the theraccine, regardless of MHC phenotype, perhaps through upregulation of MHC and tumor epitopes on the autochthonous tumor. PMID- 8368735 TI - Evaluation of vaccinia viral lysates as therapeutic vaccines in the treatment of melanoma. AB - Patients who develop metastases from melanoma in regional lymph nodes are known to be at high risk of developing further recurrences after surgical removal of the lymph node metastases. This study examines whether immunization over a two year period with a vaccine made from vaccinia viral lysates of an allogeneic melanoma cell (VMCL), following surgical removal of lymph node metastases, would help prevent the development of distant metastases and improve survival from the disease. Eighty patients treated with VMCL alone and followed for a minimum of 5.5 years had improved survival compared with that of a historical control group of 151 patients and a concurrent nonrandomized group of 55 patients. Similarly, survival of 102 patients treated with VMCL plus low dose cyclophosphamide for a minimum of 3.5 years was superior to that of the historical control group but not to that of the group treated with VMCL alone. Improvement in survival measured from the date of removal of the primary tumor was still evident. Analysis of subsets of patients showed that VMCL treatment appeared to benefit patients irrespective of the number of lymph nodes involved and whether surgery was carried out near to (synchronous metastases) or some time after removal of the primary (delayed metastases). Analysis of two additional aspects provided further evidence for a biologic effect of the vaccine. One was an apparent alteration in distribution of metastases with a lower incidence of cutaneous metastases relative to visceral metastases in VMCL-treated patients. The second was a change in time to development of recurrences with a higher proportion of metastases occurring after 2 years in the treated patients. Of a projected 400 patients, 384 were entered into a randomized control (phase III) study to further evaluate this treatment. An interim analysis gave no reason for premature closure of the trial. This next analysis is scheduled for 9 months after closure of the trial. PMID- 8368736 TI - Clinical trials with VMO for melanoma. PMID- 8368737 TI - Lessons from autoimmunity. AB - Autoimmunity is a common occurrence as shown by the human potential to make autoantibodies. New syndromes resembling clinical autoimmune diseases and arising from presumed immunotoxic exposure are presented. Future experimentation should attempt to harness this autoimmune potential to create more effective anticancer vaccines. PMID- 8368738 TI - Immunogenicity and clinical activity of a polyvalent melanoma antigen vaccine prepared from shed antigens. PMID- 8368739 TI - Approaches to augmenting the IgG antibody response to melanoma ganglioside vaccines. PMID- 8368741 TI - Tumor immunology: an overview. PMID- 8368740 TI - Human tumor-associated antigen mimicry by anti-idiotypic antibodies. Immunogenicity and clinical trials in patients with solid tumors. PMID- 8368742 TI - Genetically engineered vaccines. Comparison of active versus passive immunotherapy against solid tumors. AB - Late tumor bearers (LTB), that is, mice that had tumors 3 weeks or longer, can have a selective immune dysfunction and fail to respond to target antigens expressed by the cancer cells. Such mice, however, do respond to nonmalignant cells engineered to express the rejection antigen, and they can be vaccinated with such cells to reject growing tumors. In this study, we compared the efficacy of passive immunization with that of active immunization using the engineered vaccine. An allogeneic MHC class I molecule was used as model tumor antigen. We found that active immunotherapy was only effective for small tumors in early stages of growth. In a later stage of tumor growth, active immunotherapy did not cure any mice, whereas passive immunotherapy was successful in all animals. Reasons for the failure of these LTB to respond to active vaccination with the engineered vaccine may be related to the decreased primary or secondary response we observed in these mice after active immunization. It is suggested that normal antigen-presenting cells expressing the tumor rejection antigen can elicit, in the presence of IL-2, antigen-specific T-cell responses by LTB, and that such T cells may be curative when used in adoptive therapy. We also suggest that the stage of tumor growth and the immune status of LTB more closely simulate the conditions observed in cancer patients. PMID- 8368743 TI - Novel adjuvant strategies for experimental malaria and AIDS vaccines. AB - Adjuvant research has improved the ability of biotechnology to generate novel vaccines. Numerous strategies for enhancing the immunogenicity of synthetic peptides and proteins have been identified. This overview focuses on adjuvant development and vaccine delivery systems that provide new tools for amplifying the effectiveness of ongoing malaria and AIDS vaccine development programs. In addition, some of the complex challenges and issues that have become associated with the delivery of modern vaccines in man are outlined. As adjuvant research continues to open new opportunities in vaccine development, there is renewed expectation that further generations of safe and potent vaccines will be possible against a broad spectrum of infectious agents and cancer. PMID- 8368744 TI - Immunotherapeutic strategies for cancer using poxvirus vectors. PMID- 8368745 TI - Cancer vaccines: the perspective of the Cancer Immunology Branch, NCI. AB - The Cancer Immunology Branch, NCI, is supporting a great deal of exciting research relevant to cancer vaccine development. The few areas highlighted here are representative of ongoing research opportunities, but further progress depends largely on a continued infusion of investigator-initiated ideas to realize the potential of current research areas and open new ones. PMID- 8368746 TI - Active specific immunotherapy of murine colon adenocarcinoma with recombinant vaccinia/interleukin-2-infected tumor cell vaccines. PMID- 8368747 TI - Immunization with human monoclonal antiidiotypic antibody in colorectal cancer. PMID- 8368748 TI - Immunization effect of monoclonal antibodies against tumor-associated antigens during cancer treatment. PMID- 8368749 TI - Tolerance and ways to break it. AB - The overall picture as regards cellular mechanisms in immunologic tolerance is thus clear. Thymic negative selection is an important and dominant mechanism for both CD4+ and CD8+ T cells for those antigens (and they may be very many indeed), the peptides of which get expressed within the thymus. The induction of anergy among peripheral T lymphocytes may represent an ancillary mechanism in some cases, but this is not as clear as it appeared 2 or 3 years ago. Evidently, in many cases, T cells simply ignore antigens present only within specialized organs, and these T cells, even if only of low affinity for the antigen in question, could be provoked into autoimmunity if sufficient help is provided, for example, through localized production of IL-2 or through provision of cross reactive help. B-cell tolerance is also proven and involves deletional mechanisms (most likely maturation arrest) or functional inactivation (clonal anergy). The former phenomenon dominates for self-antigens that strongly cross-link the B cell's Ig receptors and the latter for weaker negative signals. Despite these two mechanisms, clonal ignorance prevails for many self-antigens. The secondary B cell repertoire is also largely free of anti-self B cells, lack of T-cell help being a major factor in preventing the development of anti-self memory B cells. Therefore, to have the best chance of creating an immunogenic antitumor vaccine, a few simple and rather obvious rules must be followed. The antigen in question must be presented in such a way as to be palatable to "professional" antigen presenting cells, particularly dendritic cells and macrophages. Immunotherapy protocols should avoid at all costs the widespread distribution of the antigen in question through the extracellular fluids. Indeed, it is possible that widespread circulation of a tumor-associated antigen through the serum and lymph because of large-scale shedding from the tumor cell may already have created a substantial degree of tolerance to the antigen in question in both T- and B-cell populations. If that has happened, it becomes particularly important to create a cancer vaccine capable of inducing help. This may well involve coupling of the most important epitopes to some highly immunogenic and foreign carrier. A wide choice of adjuvants is available for the designer of tumor vaccines, and in this regard the cancer immunotherapy community has much to learn from the rapidly developing field of infectious disease vaccinology using recombinant and other vaccines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8368750 TI - Assessment of immunologic competence and host reactivity against tumor antigens in breast cancer patients. Prognostic value and rationale of immunotherapy development. PMID- 8368751 TI - Augmentation of T-cell response with a melanoma cell vaccine expressing specific HLA-A antigens. PMID- 8368752 TI - Transfection of TGF-beta producing tumors with IL-2 elicits tumor rejection. PMID- 8368753 TI - Coexpression of IL-2 and gamma-IFN enhances tumor immunity. PMID- 8368754 TI - Pancarcinoma T/Tn antigen detects human carcinoma long before biopsy does and its vaccine prevents breast carcinoma recurrence. PMID- 8368755 TI - Phase Ib trial of a synthetic beta human chorionic gonadotropin vaccine in patients with metastatic cancer. PMID- 8368756 TI - Adjuvant vaccination in colorectal carcinoma. PMID- 8368757 TI - Specific immunotherapy of colorectal carcinoma with Newcastle-disease virus modified autologous tumor cells prepared from resected liver metastasis. PMID- 8368758 TI - Randomized study of adjuvant immunotherapy with autologous tumor cells and BCG in renal cancer. PMID- 8368759 TI - Specific immunotherapy using a recombinant vaccinia virus expressing human carcinoembryonic antigen. PMID- 8368760 TI - Identification and characterization of a colon tumor-associated antigen. PMID- 8368761 TI - Antiidiotype (Ab2) vaccine therapy for cutaneous T-cell lymphoma. PMID- 8368762 TI - A potential surrogate marker of efficacy for a therapeutic melanoma vaccine. PMID- 8368763 TI - Enhancement of a spontaneous immune response against a B-cell lymphoma by dendritic cells leads to protection against the tumor. PMID- 8368764 TI - Clinical trials of idiotype-specific vaccine in B-cell lymphomas. PMID- 8368765 TI - Clinical responses to intralymphatic whole-cell melanoma vaccine augmented by in vitro incubation with alpha-interferon. PMID- 8368766 TI - Adjuvant activity of QS-21 isomers. AB - QS-21, a reverse-phase purified triterpene glycoside from the South American tree Quillaja saponaria, can be further resolved into two peaks when chromatographed by high performance hydrophilic interaction chromatography. These two peaks demonstrated identical pseudomolecular ion weights and fragmentation patterns when analyzed by fast atom bombardment-mass spectroscopy. Carbohydrate analysis by monosaccharide composition and linkage analysis showed that a terminal apiose in the major peak was replaced by another pentose residue in the minor peak. Hence, the two peaks were structural isomers. Dose response curves for each isomer and reverse-phase purified QS-21 were similar, with a minimum effective dose of 5 micrograms in mice. This result indicates that the portion of QS-21 containing this variation is not critical for adjuvant activity. PMID- 8368767 TI - Construction of immunogenic GD3-conjugate vaccines. PMID- 8368768 TI - Comparison of the binding parameters to melanoma cells of antihuman high molecular weight-melanoma associated antigen (HMW-MAA) monoclonal antibodies (mAb) and syngeneic anti-anti-idiotypic (anti-anti-id) mAb. PMID- 8368769 TI - Tumor escape from immune response by variation in HLA expression and other mechanisms. PMID- 8368770 TI - Tumor antigens known to be immunogenic in man. PMID- 8368771 TI - Recognition of autoantigens by patients with melanoma. PMID- 8368772 TI - The publisher's parish. PMID- 8368773 TI - Functional effects of alar cartilage malposition. AB - Nasal airway obstruction is frequently synonymous with septal deviation or inferior turbinate hypertrophy. Less readily appreciated is the fact that the mobile lateral nasal wall caudal to the bony arch can obstruct the airway, particularly at the internal or external nasal valves. External valvular incompetence can result from postsurgical or congenital causes, among the most common of which is alar cartilage malposition. Twenty-seven patients with alar cartilage malposition in a series of 61 patients (44%) treated for airway obstruction from external nasal valvular incompetence comprise this report. Rhinomanometric data demonstrate an increase in total nasal airflow from 99 +/- 17 ml (mean +/- SEM) to 190 +/- 37 ml per 14 seconds after valvular correction. Patients in whom additional septal pathology was corrected nevertheless had no significant airflow improvement over patients with external valvular reconstruction alone. Treatment principles of valvular incompetence from alar cartilage malposition are given for primary and secondary rhinoplasty patients, among which is a composite conchal cartilage/skin graft that can reconstruct a functioning lateral crus and replace a vestibular skin deficiency. Interestingly, alar cartilage relocation to correct the malposition also narrows the alar base, even when no alar wedge resection is performed. PMID- 8368774 TI - Nasal osteotomy--utilizing dual plane reciprocating nasal saw blades: a 6-year follow-up. AB - Observation of the nasal bone anatomy has demonstrated a double S-curve configuration from the base of the pyriform aperture to the medial canthus. The most common method of osteotomy uses a curved osteotome or a chisel. The movement of either is facilitated by tapping with a mallet. With this method, frequent green-stick fractures, fragmentation, and other complications have been encountered. For the last 6 years, a dual plane, curved stainless steel blade has been used to accomplish low to high osteotomies. This gives a precise lateral transverse osteotomy without medial osteotomy being required. This technique allows the operator to produce a well-defined and precise lateral osteotomy with fewer potential complications and less postoperative swelling as well as improved patient comfort. In cases of secondary rhinoplasty or old nasal trauma, sites of previous fibrous union are able to be osteotomized with precisely controlled cuts, avoiding unpredictable fragmentation or fracture lines. PMID- 8368775 TI - Augmentation mammoplasty: results of a patient survey. AB - A detailed survey on aesthetic augmentation mammoplasty was sent to patients who had undergone this procedure at the Massachusetts General Hospital between July 1973 and July 1991 to determine the incidence of postoperative complications after augmentation mammoplasty, and to qualify the factors related to patient satisfaction (n = 304). Surgical records of respondents were examined. After a mean follow-up of 8.2 years, there were no patients with known breast cancer or autoimmune disease after augmentation. Five implants (2.5%) were replaced due to leakage. Other complications were rare. Overall satisfaction was high and correlated inversely with capsular contracture ratings and elapsed time. Contracture ratings increased with time for silicone implants. Gel implants in the submuscular position were softer than subglandular ones after 5 years elapsed time. Most women are satisfied after augmentation mammoplasty, despite a significant incidence of capsular contracture. The incidence of other adverse effects after augmentation is low. Augmentation mammoplasty does not appear to be an inducer of autoimmune disease or of breast cancer. PMID- 8368776 TI - Nipple-areola reconstruction with intradermal tattoo and double-opposing pennant flaps. AB - Reconstruction of the nipple-areolar complex is an important part of postmastectomy breast reconstruction. Intradermal tattooing is effective for creating areolar pigmentation and is simpler than skin grafting. However, a simple method for the construction of a normal nipple using local tissues remains a challenge. Several techniques achieve long-term nipple projection but at the expense of complicated flap design, multidirectional scars, and often a need for skin grafting to obtain a uniform-appearing areola. Our one-stage method of nipple-areola reconstruction uses intradermal tattooing for pigmentation and double-opposing pennant flaps for nipple reconstruction. The entire procedure is simple and fast, routinely performed in < 30 minutes under local anaesthesia in the office. From September 1989 to March 1992 we performed 102 reconstructions. The method produces a realistic appearing nipple. We have had no flap necrosis. PMID- 8368777 TI - Prediction of vascular complications following free tissue transfer. AB - Thirty-five consecutive free tissue transfers were evaluated prospectively. A prediction of postoperative vascular complications was made at the time of wound closure. Two vascular complications occurred, each predicted intraoperatively. Conversely, the 33 flaps that did not develop vascular complications were correctly identified intraoperatively. Intraoperative findings that correlated with postoperative vascular complications were clinically recognizable changes in flap perfusion. PMID- 8368778 TI - Bacterial clearance capability of living skin equivalent, living dermal equivalent, saline dressing, and xenograft dressing in the rabbit. AB - Two new skin substitutes, Living Skin Equivalent (LSE) and Living Dermal Equivalent (DE), have recently been developed. In this experiment, the ability of the LSE and DE preparations to function as biological dressings in an acute wound model was tested. Forty full-thickness wounds were made in New Zealand White rabbits. Each wound was inoculated with 5 x 10(5) Staphylococcus aureus organisms. Twenty-four hours later, one of the following four dressings was applied: saline gauze, porcine-derived xenograft, LSE, or DE. Daily dressing changes and wound biopsies for bacterial counts were performed. At 96 hours after inoculation, split-thickness autograft was applied to all wounds. Skin graft take was assessed 5 days later. In all treatment groups, bacterial counts decreased over time (p = 0.02). At 72 and 96 hours after inoculation, wounds dressed with LSE or DE had significantly lower mean bacterial counts than wounds treated with xenograft dressing (p < 0.01). No significant differences were found among the LSE-, DE-, or saline-treated groups. Skin grafts took well in LSE- and DE-treated wounds. In conclusion, the LSE and DE were more effective than xenograft in reducing bacterial wound contamination in this model, thereby demonstrating their potential application as biological dressing materials. PMID- 8368779 TI - The effect of ibuprofen on microvascular thrombosis in an experimental rabbit model. AB - The efficacy of ibuprofen in reducing microvascular thrombosis in a well established experimental model was studied. Bilateral 2-mm arterial inversion grafts were constructed in the femoral arteries of New Zealand White rabbits. The experimental group (n = 40 grafts) received subcutaneous injections of ibuprofen 15 mg/kg t.i.d. beginning 1 day preoperatively and continued for 7 days postoperatively. The control group (n = 42 grafts) received injections of an equivalent volume of saline three times per day. Patency was evaluated at 7 days by the distal milking test. Seventy-three percent of the ibuprofen grafts were patent at 7 days, whereas 57% of the control grafts remained open. This difference in microvascular patency was not statistically significant. Representative scanning electron micrographs revealed a moderate reduction in aggregated platelets and overall clot density in the patent ibuprofen arterial inversion grafts compared with the patent control specimens. Although the use of ibuprofen as a sole antithrombotic agent cannot be recommended as the result of this study, it may be efficacious when used in conjunction with other agents such as dextran 40. PMID- 8368780 TI - Investigation of a biodegradable, implantable antibiotic delivery system on rate of wound infection. AB - Biodel, a bioabsorbable polymer, may be adapted to serve as an antibiotic delivery system for high local concentrations of drugs. In an autocontaminated, irradiated wound model with a high intrinsic infection rate, implanted gentamicin impregnated Biodel beads prevented wound infections in the submental area of rats. PMID- 8368781 TI - The role of alloplastic skeletal modification in the reconstruction of facial burns. AB - The external appearance of the face is largely dictated by its supporting facial skeleton. After an extensive thermal injury, the underlying facial skeleton may need to be either augmented or restored to maintain the functional and aesthetic appearance of the face. The factors that make a structural reconstruction difficult are poor vascularity and compliance of the scar tissue, extreme contractile forces of the scar, and unstable skin coverage. The use of an alloplast in the setting of facial burn scars may be one of the greatest challenges for an implant material. We reviewed our experience with the use of the Medpor porous polyethylene implant in facial burn reconstruction. This biomaterial has structural characteristics that allow for tissue ingrowth, yet it resists deformation by contractile forces. A total of 57 consecutive implants were placed in 24 patients with facial burns. Implants were used for the chin, the nose, the malar region, and as an ear framework. Patient follow-up ranged from 6 months to 3 years. Although 4 implants became exposed and 1 was thought to become infected, only 1 of the implants was removed. There were no other implant related complications. We believe that skeletal modification is an important step for a successful facial burn reconstruction. Porous polyethylene offers a promising solution for the complex reconstructive problem of using an alloplast in the environment of a facial burn. PMID- 8368782 TI - The role of facial muscle resection in reconstruction of the paralyzed face. AB - The technique of resecting the levator labii superioris alaeque nasi muscle can help improve nasal symmetry and is a useful ancillary procedure in reconstruction of the paralyzed face. In 3 patients with facial paralysis, this technique markedly changed the nasal deviation seen at rest and also affected the nasolabial angle and medial nasolabial fold. A patient report is presented. PMID- 8368783 TI - Tubed, folded radial forearm free flap for pharyngeal reconstruction and voice rehabilitation. AB - Reconstruction after total laryngectomy ideally includes restoration of voice with protected swallowing. Local flaps and tracheo-esophageal puncture with a prosthesis are widely used to accomplish this. Persistent problems, perhaps inherent to this solution, have led to the recent use of a tubed, folded radial forearm free flap for postlaryngectomy reconstruction. This flap has produced a good voice with low phonation pressures and minimal aspiration in 7 patients. A new configuration for this flap is described and 3 patients reported. Our flap's advantages include a simplified pedicle path, ease of construction, remote microanastomosis, and safer revision. Both patients with surviving flaps rapidly developed a good voice after reconstruction. Mild aspiration in 1 delayed oral intake and forced a successful revision. Our reconfigured flap may have some technical advantages, survives to length, and restores a good voice without significant aspiration. This and its simple care make it popular with patients. Development of this flap holds promise of more complete reconstruction after total laryngectomy. PMID- 8368784 TI - Carpal tunnel release complicated by necrotizing fasciitis. AB - We report a 31-year-old diabetic woman who underwent carpal tunnel release for median nerve compression followed by a laparoscopic tubal ligation. The procedure was complicated by a severe postoperative necrotizing fasciitis infection of the carpal tunnel release incision. This has not been previously reported. The wound was poorly responsive to antibiotic therapy and serial wound debridements. Control of the woman's infection required total excision of the palmar skin and fascia. Complicating factors in this case included the woman's long history of insulin-dependent diabetes and a concomitant clean-contaminated procedure. PMID- 8368786 TI - "Off-the-shelf" techniques for continuous tissue expansion. AB - Since modern tissue expansion was introduced in 1976, it has proved to be a safe and effective technique for obtaining extra tissue where traditionally distant flaps and grafts had been used. However, the lengthy expansion times and prolonged gross deformity of conventional expansion protocols have often deterred both physician and patient from choosing this reconstructive option. Over the past decade, attempts to shorten the total expansion time have centered around decreasing the time intervals between injections. Recently, researchers at Washington University have developed the technique of continuous tissue expansion (CTE), using a custom-designed, computerized pump. With CTE, expansion times have been shortened from 2 weeks to 3 days. At our institution, we have demonstrated that CTE can be safely and economically performed with the use of equipment already existent in most medical centers. We describe the equipment and technique and present two cases of successful clinical application of CTE. PMID- 8368785 TI - Two unusual postburn reconstructions using tissue expansion: one exogenous and one endogenous. PMID- 8368787 TI - Tourniquet-related hypotension in venous stasis ulcer excision. AB - Extremity tourniquets are widely used to achieve bloodless dissection in the surgical field. Excision of venous stasis ulcers (VSU) is aided by tourniquet use because of large dilated veins associated with venous stasis disease. We present 3 patients with hypotensive shock occurring 10 to 15 minutes after tourniquet release after excision of venous stasis ulcers. All patients had long histories of venous stasis changes and two-thirds had prior histories of deep vein thromboses and pulmonary embolism. Mean tourniquet inflation time was 34 minutes and there were electrocardiographic changes in two-third of the patients. All patients responded rapidly to standard resuscitation measures and in all 3 postoperative testing for pulmonary embolus and myocardial infarction was negative. Wound cultures revealed no organisms in 1 patient, mixed Gram-positive cocci in another, and greater than 10(5) Serratia marcescens in the third patient. Although small decreases in blood pressure and blood pH, and increases in blood lactate, PcO2, and creatinine phosphokinase, are normally associated with the use of extremity tourniquets, hypotensive shock has not been reported. The combined effect of tourniquet ischemia and venous stasis changes may cause hypotensive shock by (1) an endotoxic bolus upon tourniquet release, (2) pulmonary microembolization of platelet, fibrin, and leukocyte aggregates causing vasoactive substance release, and (3) synergistic effects of platelet-activating factor, a known mediator of endotoxic shock. The untoward events noted in these patients may be prevented by (1) proximal to distal dissection of the ulcer with initial ligation of large veins, (2) pretreatment with steroids and/or platelet activating factor antagonists, and/or (3) slow release of the tourniquet. PMID- 8368788 TI - The cross-leg flap revisited. AB - Although free flaps are currently the gold standard for distal lower extremity reconstruction, situations occasionally arise when alternative methods are needed. We present three cases of cross-leg flaps, which have been modernized with current external fixation technology and current understanding of vascular anatomy. All cross-leg flaps were based on the axial blood supply of the posterior descending subfascial cutaneous branch of the popliteal artery. This axial flap afforded considerable length and well-vascularized tissue. All patients were placed in external fixation devices. Adjacent lower extremity joints were exercised during the period of attachment. There were no major complications or flap failures. All patients were ambulatory postoperatively. We conclude that the cross-leg flap, using external fixation techniques and axially based flaps, can be successfully and expeditiously used to cover defects of the lower extremities. PMID- 8368789 TI - Giant cell granuloma of the facial bones. AB - Giant cell granuloma of the facial bones is a benign, reparative metabolic lesion that usually presents as a painful, expansile mass of the mandible. However, 1 of our patients had the extremely rare findings of multiple other facial bone involvement. In this series of 3 patients followed for > 6 years, the combination of biopsy and clinical presentation provided a stereotypical pattern that enabled an accurate diagnosis in all cases. Our patients were treated successfully with aggressive, but not radical, therapy, excisional curettage, and cauterization of remaining bone. Satisfactory reconstruction and stabilization of the mandible and maxilla were achieved with split rib grafts. The rib graft reconstruction and new bone formation provided excellent contour at 6 years in our adult patients and resulted in normal mandibular growth in the child we treated and followed for 12 years. PMID- 8368791 TI - Re: A newly designed minigraft to achieve angularity and projection of the nasal tip: the asymmetrical bipyramidal graft. PMID- 8368790 TI - Re: Squamous cell carcinoma following breast augmentation. PMID- 8368792 TI - [Percutaneous angioscopy and angioplasty in the treatment of arteriopathies of the lower limbs]. AB - Since 1987, the authors have routinely combined angioscopy with angioplasty of peripheral arteries. In a series of 251 angioplasties carried out in 191 patients, angioscopy was found to be more specific and more sensitive than arterial angiography in the etiological diagnosis of arterial stenoses and/or obstructions. Angioscopic findings modified the angioplasty procedure in 29% of cases. Using an inflatable catheter remains the most commonly used approach (230 cases); in 10 cases, this was preceded by thromboaspiration and in 4 cases by dotterization. Angioscopic support was useful in carrying out difficult manoeuvres (monitoring of the angioplasty in 4 cases, correct orientation of the guide into the lumen in 14 cases, installation of an endoprosthesis in 9 cases, arterial biopsy in 5 cases and sampling of an atheroma in 8 cases). PMID- 8368793 TI - [Percutaneous endoluminal angioplasty using balloon catheter in peripheral arteriopathies of the lower limbs]. AB - Dilatation using an inflatable catheter is the best and most commonly used percutaneous endoluminal treatments for arteriopathy of the legs. We now have enough follow-up to say that it has acquired a position beside surgery without opposing this as the two methods are often complementary. The indications have been extended and the results, for certain types of lesion, are similar to those achieved with surgery, with the advantages specific to this method. Complications remain limited and can often be dealt with during this procedure by means of other percutaneous methods (installation of endoprostheses, fibrinolysis, thromboaspiration). PMID- 8368794 TI - [Transcranial Doppler: methodology and indications in 1993]. AB - Transcranial Doppler ultrasound is a new non-invasive method of exploration which through the use of low frequencies and transcranial windows is able to investigate the main vessels in the Willis polygon. It now has a variety of applications: diagnosis of stenoses and intracranial occlusions, assessment of the intracerebral impact of stenoses and occlusions of the internal carotid artery, monitoring of the middle cerebral artery in situations involving intensive care or carotid surgery, diagnosis of cerebral arteriovenous malformations, the diagnosis of brain death and the follow-up of secondary spasm due to meningeal hemorrhage. The combination of continuous Doppler and ultrasound scan with a transcranial Doppler scan is able to modify the indications for an arterial angiography, notably in cerebral ischemic disease. Its non-invasive nature and convenience will favor its future development for diagnostic purposes and, above all, for short-term monitoring or periodic long-term check-ups. PMID- 8368795 TI - [Delayed angioplasty for residual stenosis following thrombolyzed infarction: arterial permeability and left ventricular function after 6 months]. AB - At medium term, the results of delayed angioplasty (DA) following intravenous thrombolysis (IVT) in terms of arterial permeability but particularly of left ventricular function (LVF) is still poorly understood and is the subject of this prospective study. Over 18 months, 76 patients underwent DA for the residual stenosis on day 8 +/- 5 with complete and partial success rates of 88.2% and 11.8% respectively. Rapid reocclusion (< 48 hours) was documented in 9.2% of cases. After 6 months, there had been no deaths and no recurrence of infarction but a recurrence of angina in 23.7% of cases. Angiographic monitoring, carried out in 56 cases (73.7%) after 6 +/- 2.4 months identified 21 restenosis (37.5%) and 6 re-occlusions (10.7%). 12 of the restenosis were successfully re-dilated. The effect on LV function was investigated in 50 patients. In the absence of reocclusion, the ejection fraction and the kinetics of the infarcted territory were improved; significant restenosis (> 60% by digital densitometry) did not appear to offset these improvements. In addition to the maintenance of arterial permeability, the possibility of functional recovery appears to be conditioned by the degree of contractile abnormality observed during the initial ventriculography. Despite the absence of restenosis after 6 months, the occurrence on day 6 of akinesia or above all of dyskinesia reduces the chances of contractile improvement with as a corollary more marked LV changes. PMID- 8368796 TI - [Myocardial ischemia caused by the injection of dipyridamole followed by low level exertion on an exercise bicycle]. AB - The purpose of this study was the feasibility, safety and analysis of the ischemic nature of the association of an injection of dipyridamole and an exercise test at low level exertion on an exercise bicycle for 4 minutes. The ischemic nature of this combination was assessed on the basis of three criteria: the onset of angina-type pain, electrical changes and scintigraphic abnormalities. The test could be carried out by all patients and the most common adverse events were headache (6.5%) and heartburn (3.5%). The 17 patients in this study who had one or more stenoses in excess of 70% presented with angina-type pain (3/17); electrical abnormalities (9/17) and scintigraphic abnormalities in all cases. Of the six patients who had lesions between 50 and 70%, 1 presented with angina symptoms, 2 with electrical abnormalities and 5 with scintigraphic abnormalities. Seven patients in this study showed no significant lesions when subjected to coronary artery angiography. However, angina-type pain and electrical signs were observed in 2 cases and one false positive result by scintigraphy. This study shows that it is possible to combine the injection of dipyridamole with an exercise test involving a low level of exertion on an exercise bicycle which gives a good diagnostic value to the CT scan. The frequency of clinical and electrical signs of ischemia makes it necessary to take the same precautions as for a peak exercise test. PMID- 8368797 TI - [A new cause of torsades de pointes: combination of terfenadine and troleandomycin]. AB - The authors report a case of wave-burst arrhythmia which occurred during combined treatment with terfenadine and troleandomycin. After the treatment had been stopped and the QT interval returned to normal, terfenadine treatment was reintroduced with no major change in repolarization. However, as soon as troleandomycin was associated, there was a significant and progressive prolongation of QT. Normal repolarization was restored again with troleandomycin alone. These findings suggest drug interaction between terfenadine and troleandomycin. Although it is not possible to carry out serum assays of terfenadine, one possible physiopathological hypothesis would be an overdose of terfenadine. Terfenadine undergoes hepatic oxidative metabolism involving the cytochrome P450 pathway and troleandomycin inhibits cytochrome P450. In the literature, a case has already been described of wave-burst arrhythmia related to terfenadine overdose when associated with a cytochrome P450 inhibitor. PMID- 8368798 TI - [Late complication of blunt injuries of the thorax: acute pericarditis. Apropos of a case]. AB - The authors report a case of closed trauma of the thorax, complicated after a symptom-free period by acute pericarditis, combined with pleural effusion. The clinical outcome was favorable and the pericardial effusion, which was considerable at the first ultrasound scan, spontaneously recovered fully. The incidence of this delayed complication of closed trauma of the thorax is unknown. Its mechanism, related to that of the Dresler syndrome and post-pericardiotomy syndrome differs from that of initial hemopericardium which is of mechanical origin. This case highlights the capital importance of ultrasound in the diagnosis and assessment of cardiac complications of thoracic trauma. PMID- 8368799 TI - [Rhabdomyolysis caused by pravastatin and type 1 macrocreatine kinase]. AB - The authors report a case of rhabdomyolysis which occurred in a 61 year old woman who was receiving pravastatin and who was also found to present with type 1 macrocreatine kinase. Drug induced rhabdomyolysis is common, particularly with HMG Coenzyme A reductase inhibitors. The authors describe the onset of an adverse effect of this type with pravastatin, a recently marketed drug, as has been previously described for lovastatin and simvastatin. The concomitant detection of macrocreatine kinase, the incidence of which is estimated to be between 2 and 5% in the population, raises the question of whether rhabdomyolysis of this type may occur preferentially in patients with this biological anomaly. PMID- 8368800 TI - [The cardiologist as consultant to the anesthetist]. AB - The combination of surgery and heart disease is common. The incidence of both heart disease and surgery increase with the age of patients. However, the surgical risk in the cardiac patient and particularly in the coronary or heart failure patient is considerably aggravated. Surgery is a major factor in cardiac decompensation, which can accelerate the progress of the disease. Pre-anesthetic cardiological consultation is therefore an important part of the evaluation and preparation of the patient before surgery. This is carried out at the request of the anesthetist and can provide a diagnosis or adapt a treatment and above all define the cardiovascular competence of the patient. Diagnostic and therapeutic means available to the cardiologist are essential in defining and if possible reducing the cardiac handicap of patients before the hemodynamic challenge represented by the combination of anesthesia and surgery. PMID- 8368801 TI - [Spontaneous coronary dissection. Apropos of 2 cases]. AB - Spontaneous coronary dissection is a rare and still poorly understood pathological disease entity; the authors report two cases in which the diagnosis was reached in the context of incipient necrosis in young patients. A review of the literature reveals the main characteristics of this problem: the clinical aspect is generally that of acute coronary failure with the constitution of an infarction. The subjects are young with no risk factor but some cases of combination with a disease affecting the elastic tissue have been described. Female gender and the post-partum phase are promoting factors. Diagnosis was long established by means of autopsy but can now be based on coronary angiography. Histologically, the lesion is a hematoma which dissects the arterial wall between the internal two thirds and external third of the media. The main etiological hypothesis is acquired or congenital fragility of the media, which promotes the formation of a dissecting hematoma, however the triggering phenomenon remains poorly understood. PMID- 8368802 TI - Optical density profile analysis of trypsin-Giemsa bands in human X-chromosomes. AB - Mean Optical Density (M.O.D.) determination of six G-bands on X-chromosomes was performed on 45 patients with Turner's syndrome and compared with X-chromosomes from women controls with a normal karyotype by a Chromosome Image Analysis System. Density profiles were constructed to obtain standard values for the staining intensity and frequency of occurrence of chromosome bands. Statistical analysis showed that the M.O.D. were significantly different for Xq12, Xq21, Xq25 and Xq27 G-bands between the Turner and Control groups. Most within-group differences were small and appeared not to be statistically significant. PMID- 8368803 TI - Barriers to gene flow estimated by surname distribution in Italy. AB - Surname distributions were studied in order to reconstruct human migration patterns. Zones of sharp change in surname frequencies--presumably barriers to gene flow--were detected by the statistical technique of wombling (Barbujani et al. 1989), using data from consanguineous marriages (1910-64) collected from 280 Italian dioceses which we grouped into 80 provinces. The 28 observed surname boundaries were compared with physical (geographical) and cultural (linguistic) barriers, and with boundaries detected from distributions of 57 alleles in the same territorial subdivisions. Genetic and surname boundaries had similar locations, as expected given the analogy in the inheritance mechanism of genes and surnames. Physical barriers seemed to be the main cause of gene flow reduction. However, cultural factors alone (e.g. linguistic ones) also determined barriers that delimited areas of homogeneous gene (and surname) frequency probably due to increased endogamy. The observed similarity between spatial patterns of surnames, genes and languages supports the hypothesis of the co evolution of genetic and linguistic variation. PMID- 8368804 TI - Inference of the strength of genotype-disease association from studies comparing offspring with and without parental history of disease. AB - The association between genetic polymorphisms and a multifactorial disease is generally investigated by case-control studies. However, inference about the genotype-disease association can also be drawn from studies comparing offspring having a parental history of disease with offspring having no parental history. In such studies, differences in genotype frequencies between the two groups of offspring will reflect a different transmission of alleles from affected and unaffected parents. We showed that in offspring studies, the odds ratios (ORs) associated with heterozygous and homozygous genotypes are related by the formula: OR(het) = (OR(hom) + 1)/2. These ORs depend only on the allele frequencies in affected and unaffected parents, and not on the pattern of genotype-disease association. Under simple patterns of association, it is possible to infer from the ORs observed among offspring, the expected ORs for the disease. The decrease of power of offspring studies by comparison with classical case-control studies is evaluated, and an application is given on the association between the apoE polymorphism and coronary heart disease. PMID- 8368805 TI - Power comparison of various sibship tests of association. AB - There are several tests available for use with family studies to test if there is significant evidence of association with a particular disease gene locus, especially of HLA. We have used large simulations to compare the powers of tests using criteria N, R, T, PR, WP and some new tests involving both affecteds and unaffecteds in a sibship. It was found that tests using both affected and unaffected siblings were often more powerful. PMID- 8368806 TI - Estimation of the intraclass correlation coefficient. AB - When families have different numbers of offspring, the maximum likelihood procedure for estimating the intraclass correlation is iterative, requiring considerable computation. Occasionally, the iterations do not even converge. To overcome this difficulty, several non-iterative estimators have been proposed by Smith (1956). However, to choose from among these estimators, some prior knowledge of the intraclass correlation is needed. In this paper, a combination estimator is proposed. The asymptotic variance of this estimator is given and compared with those of the two most commonly used estimators. The comparison shows that the combination estimator always performs better than the uniform weight estimator and the loss in efficiency is not more than 7% when it is used in place of Fisher's estimator. PMID- 8368807 TI - Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7. AB - Informative polymorphisms have been very difficult to detect in the elastin gene, and this has hampered the analysis of heritable connective tissue disorders, notably the Marfan syndrome. We have recently detected a dinucleotide repeat polymorphism in intron 17 of the human elastin gene consisting of 8 alleles with sizes between 161 and 175 bp. Analysis of 540 chromosomes from unrelated Caucasian individuals revealed a bimodal frequency distribution typical of (dC dA)n.(dG-dT)n repeat polymorphisms, with allele frequencies ranging from 0.004 (161 bp) to 0.574 (163 bp). As the elastin gene was originally assigned to chromosome 2q31-ter and because more recent data have suggested an assignment to 7q11.1-21.1, we have genotyped a sub-set of the CEPH pedigrees and carried out pairwise linkage analysis with markers on chromosomes 7 and 2. Lod-scores of between +3.70 and +13.69 were obtained with markers spanning 7p13-q22.1, whilst negative lod-scores were observed with the chromosome 2 markers. Analysis of type II human ovarian teratomas placed the elastin gene within 11 cM of the centromere on chromosome 7. Additionally, we detected the dinucleotide repeat in human rodent cell hybrids containing chromosome 7, but not those containing chromosome 2. These data confirm the assignment of elastin to chromosome 7 and provide a new, highly informative marker for the analysis of heritable disorders of connective tissue for which elastin is a candidate gene. PMID- 8368808 TI - You can have my organs, but please make sure I'm dead before you take them. PMID- 8368809 TI - Instrument counts. PMID- 8368810 TI - HIV positive patients. PMID- 8368811 TI - Organ procurement surgery. What perioperative nurses can expect. PMID- 8368812 TI - Organ donation. Barriers, religious aspects. PMID- 8368813 TI - Living related liver transplants. A solution to donor shortage in pediatric patients. PMID- 8368814 TI - Radical ilioinguinal lymph node dissection. Treating malignant melanoma. PMID- 8368815 TI - Transurethral prostate resection. A frustration-free surgical method. PMID- 8368817 TI - Protecting the phrenic nerve during open heart surgery. PMID- 8368816 TI - Aseptic technique monitoring. A quality improvement tool in the OR. PMID- 8368818 TI - OR time delays. A time management plan that works. PMID- 8368819 TI - Communicating effectively with elderly surgical patients. AB - Effective communication promotes trusting, productive nurse/patient relationships. It is the perioperative nurse's responsibility to establish effective communication with each patient. Perioperative nurses strive to provide quality care to all patients, including the elderly. Communication barriers often do exist, however, between nurses and elderly patients. Perioperative nurses are challenged, therefore, to recognize potential communication barriers and to manage each nurse/patient relationship accordingly. Clear communication between nurse and patient enhances the elderly patient's ability to progress smoothly through surgery and recovery. PMID- 8368820 TI - Proposed recommended practices. Product evaluation and selection for the perioperative setting. Recommended Practices Committee, Association of Operating Room Nurses, Inc. PMID- 8368821 TI - Proposed recommended practices. Monitoring the patient receiving local anesthesia. Recommended Practices Committee, Association of Operating Room Nurses, Inc. PMID- 8368822 TI - ANA Code for Nurses with Interpretive Statements--explications for perioperative nursing. PMID- 8368824 TI - The operating room as a theater--a relevant metaphor. AB - Any metaphor can be stretched to absurdity. Nonetheless, the operating room as a theater can be a relevant and useful analogy. In the OR theater, the play is always a drama, sometimes a tragedy, occasionally even a comedy of errors, but never, never is it a Broadway musical. PMID- 8368823 TI - Discussion of the Joint Commission on Accreditation of Healthcare Organizations' Agenda for change. PMID- 8368825 TI - Do-not-resuscitate orders in the OR. PMID- 8368826 TI - Analysis of the Bradyrhizobium japonicum hemH gene and its expression in Escherichia coli. AB - Complementation analysis showed that the Bradyrhizobium japonicum hemH gene was both necessary and sufficient to rescue mutant strains I110ek4 and I110bk2 in trans with respect to hemin auxotrophy, protoporphyrin accumulation, and the deficiency in ferrochelatase activity. The B. japonicum hemH gene was expressed in an Escherichia coli T7 expression system and yielded a 39-kDa protein, which was consistent with the predicted size of the deduced product. The overexpressed protein was purified and shown to contain ferrochelatase activity, thereby demonstrating that the hemH gene encodes ferrochelatase. When expressed from the lac promoter, the B. japonicum hemH gene was able to complement the enzyme activity of a ferrochelatase-defective E. coli mutant, and it also conferred hemin prototrophy on those cells. These latter findings confirm the identity of the hemH gene product and demonstrate that B. japonicum ferrochelatase can interact with the E. coli heme synthesis enzymes for heme formation in complemented cells. PMID- 8368827 TI - Analysis of Tox5 gene expression in Gibberella pulicaris strains with different trichothecene production phenotypes. AB - The Tox5 gene encodes trichodiene synthase, the first unique enzyme in the trichothecene biosynthetic pathway. In Gibberella pulicaris R-6380, the level of Tox5 mRNA was found to increase 47-fold in early stationary phase. Sequence analysis of the Tox5 promoter regions from geographically distinct strains of G. pulicaris revealed the existence of two Tox5 alleles (Tox5-1 and Tox5-2). All G. pulicaris strains that produce high levels of trichothecenes in liquid culture carry a 42-nucleotide (nt) tandem repeat sequence (Tox5-1) in the Tox5 promoter region, whereas strains that produce low levels of trichothecenes carry a single copy of this sequence (Tox5-2). A genetic cross between high- and low-level trichothecene producers resulted in the cosegregation of higher-level trichothecene production with the Tox5-1 allele. To determine the importance of the 42-nt repeat sequence in the regulation of Tox5 expression, reporter gene constructs carrying either the Tox5-1 or the Tox5-2 promoter region fused to the beta-galactosidase gene of Escherichia coli were introduced into the high-level trichothecene-producing strain, R-6380. Expression of reporter gene activity in transformants was found to be regulated in a manner similar to Tox5 expression but appeared to be independent of the 42-nt sequence copy number. These results indicate that transcriptional controls play an important role in the regulation of Tox5 expression and that genes involved in trichothecene biosynthesis in G. pulicaris may be linked to Tox5. PMID- 8368828 TI - Survival and growth of Escherichia coli O157:H7 in ground, roasted beef as affected by pH, acidulants, and temperature. AB - A study was undertaken to determine the fate of Escherichia coli O157:H7 in ground, roasted beef as influenced by the combined effects of pH, acidulants, temperature, and time. There was essentially no change in the viable population of E. coli O157:H7 when beef salads (pH 5.40 to 6.07) containing up to 40% mayonnaise were incubated at 5 degrees C for up to 72 h. At 21 and 30 degrees C, significant (P < or = 0.05) increases in populations of the organism occurred in salads containing 16 to 32% mayonnaise (pH 5.94 to 5.55) between 10 and 24 h of incubation. Death was more rapid as the pH of acidified beef slurries incubated at 5 degrees C was decreased from 5.98 to 4.70. E. coli O157:H7 grew in control slurries (pH 5.98) and in slurries containing citric and lactic acids (pHs 5.00 and 5.40) incubated at 21 degrees C for 24 h; decreases occurred in slurries acidified to pHs 4.70, 5.00, and 5.40 with acetic acid or pH 4.70 with citric or lactic acid. At 30 degrees C, populations decreased in slurries acidified to pHs 4.70 and 5.00 with acetic acid. Citric and lactic acids failed to prevent significant increases in populations in slurries at pH 4.70 to 5.40 between 10 and 24 h of incubation. The order of effectiveness of acidulants in inhibiting growth was acetic acid > lactic acid > or = citric acid. The same order was observed for inactivation of E. coli O157:H7 in acidified (pH 5.00) beef slurry heated at 54 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368829 TI - Characterization of the methanotrophic bacterial community present in a trichloroethylene-contaminated subsurface groundwater site. AB - Groundwater, contaminated with trichloroethylene (TCE) and tetrachloroethylene (PCE), was collected from 13 monitoring wells at Area M on the U.S. Department of Energy Savannah River Site near Aiken, S.C. Filtered groundwater samples were enriched with methane, leading to the isolation of 25 methanotrophic isolates. The phospholipid fatty acid profiles of all the isolates were dominated by 18:1 omega 8c (60 to 80%), a signature lipid for group II methanotrophs. Subsequent phenotypic testing showed that most of the strains were members of the genus Methylosinus and one isolate was a member of the genus Methylocystis. Most of the methanotroph isolates exhibited soluble methane monooxygenase (sMMO) activity. This was presumptively indicated by the naphthalene oxidation assay and confirmed by hybridization with a gene probe encoding the mmoB gene and by cell extract assays. TCE was degraded at various rates by most of the sMMO-producing isolates, whereas PCE was not degraded. Savannah River Area M and other groundwaters, pristine and polluted, were found to support sMMO activity when supplemented with nutrients and then inoculated with Methylosinus trichosporium OB3b. The maximal sMMO-specific activity obtained in the various groundwaters ranged from 41 to 67% compared with maximal rates obtained in copper-free nitrate mineral salts media. This study partially supports the hypothesis that stimulation of indigenous methanotrophic communities can be efficacious for removal of chlorinated aliphatic hydrocarbons from subsurface sites and that the removal can be mediated by sMMO. PMID- 8368830 TI - Purification, gene cloning, amino acid sequence analysis, and expression of an extracellular lipase from an Aeromonas hydrophila human isolate. AB - A structural gene which codes for an extracellular lipase (EC 3.1.1.3) in Aeromonas hydrophila H3, which was isolated from a female hospitalized patient, was cloned in Escherichia coli by using pBR322 as a vector. Lipase purified from both A. hydrophila culture supernatant and the periplasmic fluids of E. coli containing the lip determinant in the original clone (plasmid pLA2) showed an M(r) of 67,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which agrees with the M(r) determined by Sephacryl S-200 chromatography. Regarding substrate specificity, the optimum chain lengths for the acyl moiety were C6 for ester hydrolysis and C6 and C8 for triacylglycerol hydrolysis. Sequence analysis showed a major open reading frame of 2,052 bp, which predicts a polypeptide with an M(r) of 71,804. The polypeptide was found to contain an amino acid sequence (V-H-F-L-G-H-S-L-G-A) which is highly preserved among lipases. PMID- 8368831 TI - Clostridium perfringens and somatic coliphages as indicators of the efficiency of drinking water treatment for viruses and protozoan cysts. AB - To find the most suitable indicator of viral and parasitic contamination of drinking water, large-volume samples were collected and analyzed for the presence of pathogens (cultivable human enteric viruses, Giardia lamblia cysts, and Cryptosporidium oocysts) and potential indicators (somatic and male-specific coliphages, Clostridium perfringens). The samples were obtained from three water treatment plants by using conventional or better treatments (ozonation, biological filtration). All samples of river water contained the microorganisms sought, and only C. perfringens counts were correlated with human enteric viruses, cysts, or oocysts. For settled and filtered water samples, all indicators were statistically correlated with human enteric viruses but not with cysts or oocysts. By using multiple regression, the somatic coliphage counts were the only explanatory variable for the human enteric virus counts in settled water, while in filtered water samples it was C. perfringens counts. Finished water samples of 1,000 liters each were free of all microorganisms, except for a single sample that contained low levels of cysts and oocysts of undetermined viability. Three of nine finished water samples of 20,000 liters each revealed residual levels of somatic coliphages at 0.03, 0.10, and 0.26 per 100 liters. Measured virus removal was more than 4 to 5 log10, and cyst removal was more than 4 log10. Coliphage and C. perfringens counts suggested that the total removal and inactivation was more than 7 log10 viable microorganisms. C. perfringens counts appear to be the most suitable indicator for the inactivation and removal of viruses in drinking water treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368832 TI - Effects of temperature and salinity on the survival of Vibrio vulnificus in seawater and shellfish. AB - Sterilized seawater was used to assess the effects of temperature and salinity on the survival of Vibrio vulnificus. In the temperature range of 13 to 22 degrees C, numbers of V. vulnificus increased during the 6-day incubation. Temperatures outside this range reduced the time of V. vulnificus survival in sterile 10-ppt seawater. At these restrictive temperatures, V. vulnificus numbers were reduced by 90% after 6 days of incubation. Incubation between 0.5 and 10.5 degrees C demonstrated that V. vulnificus survives poorly below 8.5 degrees C. At salinities between 5 and 25 ppt and at 14 degrees C, V. vulnificus numbers actually increased or remained unchanged after 6 days of incubation. At salinities of 30, 35, and 38 ppt, numbers of V. vulnificus decreased 58, 88, and 83%, respectively. V. vulnificus could not be recovered from deionized water, indicating lysis. When a rifampin-resistant strain of V. vulnificus was used to inoculate sterilized and unsterilized seawater (20 ppt, 20 degrees C), numbers increased in sterile seawater but decreased to undetectable levels in 14 days in the unsterilized seawater, indicating that biological factors may play a role in the survival of V. vulnificus in the environment. Since our studies demonstrated sensitivity to low temperatures, the survival of V. vulnificus in naturally contaminated oysters at temperatures of 0, 2, and 4 degrees C was also determined. Numbers of endogenous V. vulnificus in oyster shellstock increased by more than 100-fold in shellstock stored at 30 degrees C but were reduced approximately 10- and 100-fold after 14 days at 2 to 4 degrees C and 0 degrees C, respectively. We conclude that both biological and physicochemical factors are important to the survival of V. vulnificus in the environment and that temperature is critical to controlling its growth in oyster shellstock. PMID- 8368833 TI - Effects of nutrients on exopolysaccharide production and surface properties of Aeromonas salmonicida. AB - Extracellular polysaccharide (EPS) and capsular polysaccharide (CPS) production by Aeromonas salmonicida A450 and the influence of the capsule on cell surface properties were studied. A. salmonicida did not produce CPS or EPS when glucose, phosphate, magnesium chloride, or trace mineral components were absent from the medium. The addition of yeast extract improved capsule production. Neither EPS nor CPS formation depended on the C/N ratio, although it appeared to be influenced by the level of carbon and nitrogen in the culture. Both EPS and CPS production started at the end of the logarithmic growth phase. The amounts of EPS and CPS produced were not influenced by temperature changes between 15 and 20 degrees C and was maximal from pH 7 to 7.5. Cell surface properties were strongly influenced by capsule production; high CPS production was associated with enhanced cell hydrophilicity and autoagglutination. The effect of CPS on cell surface properties was independent of the presence of the surface protein array (A-layer). PMID- 8368834 TI - Structural stability of Bacillus thuringiensis delta-endotoxin homolog-scanning mutants determined by susceptibility to proteases. AB - Forty homolog-scanning (double-reciprocal-crossover) mutant proteins of two Bacillus thuringiensis delta-endotoxin genes (cryIAa and cryIAc) were examined for potential structural alterations by a series of proteolytic assays. Three groups of mutants could be identified. Group 1, consisting of 13 mutants, showed no delta-endotoxin present during overexpression conditions in Escherichia coli (48 h at 37 degrees C, with a ptac promoter). These mutants produced full-sized delta-endotoxin detectable by polyacrylamide gel electrophoresis with Coomassie blue staining or Western immunoanalysis after 24 h of growth but not after 48 h, suggesting sensitivity to intracellular proteases. Group 2 consisted of 13 mutants that produced stable delta-endotoxins that were completely digested by 2% bovine trypsin. In contrast, native delta-endotoxin produces a 65,000-Da trypsin resistant peptide, which is the active toxin. Group 3 mutants expressed delta endotoxin and trypsin-stable toxins, similar to the wild type. In this study, 12 group 3 mutant toxins were compared with wild type toxins by thermolysin digestion at a range of temperatures. The two wild-type toxins exhibited significant differences in thermolysin digestion midpoints. Among the group 3 mutants, most possessed significantly different protein stabilities relative to their parental toxins. Two of the group 3 mutants were observed to have exchanged the thermolysin sensitivity properties of the parental toxins. PMID- 8368835 TI - Stoichiometric interpretation of Escherichia coli glucose catabolism under various oxygenation rates. AB - Metabolic by-product secretion is commonly observed in oxygen-limited cultures. Oxygen limitations occur because of limits in the capacity of the respiratory system or because of the oxygenation limits of the cultivation method used. The latter restriction is of considerable practical importance since it results in a critical cell concentration above which oxygenation is insufficient, leading to by-product secretion. In this study we used a flux balance approach to determine optimal metabolic performance of Escherichia coli under variable oxygen limitations. This method uses linear optimization to find optimal metabolic flux patterns with respect to cell growth. Cell growth was defined as precursor requirements on the basis of a composition analysis. A growth-associated maintenance requirement of 23 mmol of ATP per g of biomass and a non-growth associated maintenance value of 5.87 mmol at ATP per g (dry weight)-h were incorporated on the basis of a comparison with experimental data. From computations of optimal growth increased oxygen limitations were found to result in the secretion of acetate, formate, and ethanol in that order. Consistent with the experimental data in the literature, by-product secretion rates increased linearly with the growth rate. The computed optimal growth under increasing oxygen limitation revealed four critical growth rates at which changes in the by product secretion pattern were observed. Concomitant with by-product secretion under oxygen limitations were changes in metabolic pathway utilization. The shifts in metabolism were characterized by changes in the metabolic values (computed as shadow prices) of the various redox carriers. The redox potential was thus identified as a likely trigger that leads to metabolic shifts.2+ a PMID- 8368836 TI - Stereochemistry during aflatoxin biosynthesis: conversion of norsolorinic acid to averufin. AB - A reaction sequence, norsolorinic acid (NA)-->averantin (AVN)-->5' hydroxyaverantin (HAVN)-->averufin (AVR), is the early part of a biosynthetic pathway for aflatoxins. In this study, we determined the stereochemical relationship among these metabolites by using chiral high-performance liquid chromatography. In cell-free experiments using the cytosol fraction of Aspergillus parasiticus NIAH-26, (1'S)-AVN was exclusively produced from NA in the presence of NADPH. Also, only (1'S)-AVN, and not (1'R)-AVN, served as a substrate for the reverse reaction from AVN to NA. When the microsome fraction of NIAH-26 was incubated with (1'S)-AVN in the presence of NADPH, two HAVN diastereomers and one AVR enantiomer were formed, whereas these substances were never produced from (1'R)-AVN. Moreover, (1'S,5'R)-AVR was exclusively formed from both HAVN diastereomers by the cytosol fraction in the presence of NAD. The feeding experiments using this mutant showed that aflatoxins were produced from (1'S,5'R)-AVR but not from (1'R,5'S)-AVR. These results indicate that the enzymes involved in this pathway show strict stereospecificity to their substrates and that the configuration of (1'S,5'R)-AVR leading to the formation of aflatoxins is due to the stereospecificity of NA dehydrogenase which catalyzes the reaction between (1'S)-AVN and NA. PMID- 8368837 TI - Stereochemistry during aflatoxin biosynthesis: cyclase reaction in the conversion of versiconal to versicolorin B and racemization of versiconal hemiacetal acetate. AB - (1'R,2'S)-(-)-aflatoxins are produced from racemic versiconal hemiacetal acetate (VHA) through complicated pathways, including a metabolic grid involving VHA, versiconol acetate (VOAc), versiconol, and versiconal (VHOH), and a reaction sequence from VHOH to versicolorin A (VA) through (-)-versicolorin B (VB) [or (+/ )-versicolorin C] (K. Yabe, Y. Ando, and Y. Hamasaki, J. Gen. Microbiol. 137:2469 2475, 1991; K. Yabe, Y. Ando, and T. Hamasaki, Agric. Biol. Chem. 55:1907-1911, 1991). In this study, we examined stereochemical changes of substances formed during the conversion of VHA to VA by using chiral high-performance liquid chromatography. In cell-free experiments using the cytosol of Aspergillus parasiticus NIAH-26, both (2'S)- and (2'R)-VOAc enantiomers were formed at about a 1:2 ratio from racemic VHA in the presence of NADPH and dichlorvos (dimethyl 2,2-dichlorovinylphosphate). Also, the esterase activity catalyzing the conversion of VHA to VHOH or of VOAc to versiconol did not show the stereospecificity for the 2' carbon atom of VHA or VOAc. However, when racemic VHA or racemic VHOH was incubated with the cytosol, (1'R,2'S)-(-)-VB was formed exclusively. Furthermore, only (1'R,2'S)-(-)-VB, and not (1'S,2'R)-(+) antipode, served as a substrate for desaturase activity in the microsome fraction catalyzing the conversion of VB to VA. These results demonstrate that the stereoconfiguration of bis-furan moiety in aflatoxin molecules is determined by the cyclase enzyme catalyzing the reaction from VHOH to VB, and the (1'R,2'S)-(-) configuration was further confirmed by the subsequent desaturase reaction. Remarkably, we found nonenzymatic racemization in both the (2'R)- and (2'S)-VHA enantiomers, and it was dependent upon the temperature and alkaline conditions. PMID- 8368838 TI - Degradation of nitrobenzene by a Pseudomonas pseudoalcaligenes. AB - A Pseudomonas pseudoalcaligenes able to use nitrobenzene as the sole source of carbon, nitrogen, and energy was isolated from soil and groundwater contaminated with nitrobenzene. The range of aromatic substrates able to support growth was limited to nitrobenzene, hydroxylaminobenzene, and 2-aminophenol. Washed suspensions of nitrobenzene-grown cells removed nitrobenzene from culture fluids with the concomitant release of ammonia. Nitrobenzene, nitrosobenzene, hydroxylaminobenzene, and 2-aminophenol stimulated oxygen uptake in resting cells and in extracts of nitrobenzene-grown cells. Under aerobic and anaerobic conditions, crude extracts converted nitrobenzene to 2-aminophenol with oxidation of 2 mol of NADPH. Ring cleavage, which required ferrous iron, produced a transient yellow product with a maximum A380. In the presence of NAD, the product disappeared and NADH was produced. In the absence of NAD, the ring fission product was spontaneously converted to picolinic acid, which was not further metabolized. These results indicate that the catabolic pathway involves the reduction of nitrobenzene to nitrosobenzene and then to hydroxylaminobenzene; each of these steps requires 1 mol of NADPH. An enzyme-mediated Bamberger-like rearrangement converts hydroxylaminobenzene to 2-aminophenol, which then undergoes meta ring cleavage to 2-aminomuconic semialdehyde. The mechanism for release of ammonia and subsequent metabolism are under investigation. PMID- 8368839 TI - Fate of enterohemorrhagic Escherichia coli O157:H7 in apple cider with and without preservatives. AB - A strain of enterohemorrhagic Escherichia coli serotype O157:H7 isolated from a patient in an apple cider-related outbreak was used to study the fate of E. coli O157:H7 in six different lots of unpasteurized apple cider. In addition, the efficacy of two preservatives, 0.1% sodium benzoate and 0.1% potassium sorbate, used separately and in combination was evaluated for antimicrobial effects on the bacterium. Studies were done at 8 or 25 degrees C with ciders having pH values of 3.6 to 4.0. The results revealed that E. coli O157:H7 populations increased slightly (ca. 1 log10 CFU/ml) and then remained stable for approximately 12 days in lots inoculated with an initial population of 10(5) E. coli O157:H7 organisms per ml and held at 8 degrees C. The bacterium survived from 10 to 31 days or 2 to 3 days at 8 or 25 degrees C, respectively, depending on the lot. Potassium sorbate had minimal effect on E. coli O157:H7 populations, with survivors detected for 15 to 20 days or 1 to 3 days at 8 or 25 degrees C, respectively. In contrast, survivors in cider containing sodium benzoate were detected for only 2 to 10 days or less than 1 to 2 days at 8 or 25 degrees C, respectively. The highest rates of inactivation occurred in the presence of a combination of 0.1% sodium benzoate and 0.1% potassium sorbate. The use of 0.1% sodium benzoate, an approved preservative used by some cider processors, will substantially increase the safety of apple cider in terms of E. coli O157:H7, in addition to suppressing the growth of yeasts and molds. PMID- 8368840 TI - Copper-resistant enteric bacteria from United Kingdom and Australian piggeries. AB - Thirty-three enteric isolates from Australian (Escherichia coli only) and United Kingdom (U.K.) (Salmonella sp., Citrobacter spp., and E. coli) piggeries were characterized with respect to their copper resistance. The copper resistance phenotypes of four new Australian E. coli isolates were comparable with that of the previously studied E. coli K-12 strain ED8739(pRJ1004), in that the resistance level in rich media was high (up to 18 mM CuSO4) and resistance was inducible. Copper resistance was transferable by conjugation from the new Australian isolates to E. coli K-12 recipients. DNA similarity between the new Australian isolates and the pco copper resistance determinant located on plasmid pRJ1004 was strong as measured by DNA-DNA hybridization; however, the copper resistance plasmids were nonidentical as indicated by the presence of restriction fragment length polymorphisms between the plasmids. DNA-DNA hybridization and polymerase chain reaction analysis demonstrated DNA homology between the pco determinant and DNA from the U.K.E. coli, Salmonella sp., and Citrobacter freundii isolates. However, the copper resistance level and inducibility were variable among the U.K. strains. Of the U.K. E. coli isolates, 1 demonstrated a high level of copper resistance, 4 exhibited intermediate resistance, and 16 showed a low level of copper resistance; all of these resistances were expressed constitutively. A single U.K. C. freundii isolate, had a high level of copper resistance, inducible by subtoxic levels of copper. Transconjugants from one E. coli and one C. freundii donor, with E. coli K-12 strain UB1637 as a recipient, showed copper resistance levels and inducibility of resistance which differed from that expressed from plasmid pRJ1004.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368841 TI - Effect of medium composition and sludge removal on the production, composition, and architecture of thermophilic (55 degrees C) acetate-utilizing granules from an upflow anaerobic sludge blanket reactor. AB - A thermophilic upflow anaerobic sludge blanket (UASB) reactor degrading acetate was started by applying published methods (W. M. Wiegant and A. W. A. de Man, Biotechnol. Bioeng. 28:718-77, 1986) for production of granules dominated by Methanothrix spp. The reactor was inoculated with thermophilic digested sludge. No granules were observed during the first 7 months of start-up of the UASB reactor. However, after the concentrations of potassium, phosphate, ammonium, and magnesium in the medium were gradually increased, granules developed, indicating that there was a critical concentration of one or more of the ions required for production of granules from the starting material. After several years of stable operation, the effect of removing 60% of the granular sludge was investigated. Immunologic qualitative and quantitative studies showed that removal of the granular sludge resulted in an increase in the number of the predominant methanogens, antigenically related to Methanosarcina thermophila TM-1 and Methanosarcina mazeii S-6, and Methanobacterium thermoautotrophicum delta H and GC1. These changes were accompanied by modifications of the microanatomy of the granules, as demonstrated histochemically and immunohistochemically. The results indicated that different catabolic pathways dominated in different regions of the granules, i.e., acetate oxidation in the middle of the granules, where there is a low acetate concentration, and an aceticlastic reaction in the outer surfaces, with a high acetate concentration. The results also showed that removal of granules from a UASB reactor which has been under steady-state operation for a long period can improve the reactor's performance via formation of denser and larger granules with improved microbial activities. PMID- 8368842 TI - Effects of hydrogen and formate on the degradation of propionate and butyrate in thermophilic granules from an upflow anaerobic sludge blanket reactor. AB - Degradation of propionate and butyrate in whole and disintegrated granules from a thermophilic (55 degrees C) upflow anaerobic sludge blanket reactor fed with acetate, propionate, and butyrate as substrates was examined. The propionate and butyrate degradation rates in whole granules were 1.16 and 4.0 mumol/min/g of volatile solids, respectively, and the rates decreased 35 and 25%, respectively, after disintegration of the granules. The effect of adding different hydrogen oxidizing bacteria (both sulfate reducers and methanogens), some of which used formate in addition to hydrogen, to disintegrated granules was tested. Addition of either Methanobacterium thermoautotrophicum delta H, a hydrogen-utilizing methanogen that does not use formate, or Methanobacterium sp. strain CB12, a hydrogen- and formate-utilizing methanogen, to disintegrated granules increased the degradation rate of both propionate and butyrate. Furthermore, addition of a thermophilic sulfate-reducing bacterium (a Desulfotomaculum sp. isolated in our laboratory) to disintegrated granules improved the degradation of both substrates even more than the addition of methanogens. By monitoring the hydrogen partial pressure in the cultures, a correlation between the hydrogen partial pressure and the degradation rate of propionate and butyrate was observed, showing a decrease in the degradation rate with increased hydrogen partial pressure. No significant differences in the stimulation of the degradation rates were observed when the disintegrated granules were supplied with methanogens that utilized hydrogen only or hydrogen and formate. This indicated that interspecies formate transfer was not important for stimulation of propionate and butyrate degradation. PMID- 8368843 TI - Inhibition of Listeria monocytogenes by Lactobacillus bavaricus MN in beef systems at refrigeration temperatures. AB - The ability of Lactobacillus bavaricus, a meat isolate, to inhibit the growth of three Listeria monocytogenes strains was examined in three beef systems: beef cubes, beef cubes in gravy, and beef cubes in gravy containing glucose. The beef was minimally heat treated, inoculated with L. bavaricus at 10(5) or 10(3) CFU/g and L. monocytogenes at 10(2) CFU/g, vacuum sealed, and stored at 4 or 10 degrees C. The meat samples were monitored for microbial growth, pH, and bacteriocin production. The pathogen was inhibited by L. bavaricus MN. At 4 degrees C, L. monocytogenes was inhibited or killed depending on the initial inoculum level of L. bavaricus. At 10 degrees C, at least a 10-fold reduction of the pathogen occurred, except in the beef without gravy. This system showed a transient inhibition of the pathogen during the first week of storage followed by growth to control levels by the end of the incubation period. Bacteriocin was detected in the samples, and inhibition could not be attributed to acidification. Low refrigeration temperatures significantly (P < or = 0.05) enhanced L. monocytogenes inhibition. Moreover, the addition of glucose-containing gravy and the higher inoculum level of L. bavaricus were significantly (P < or = 0.05) more effective in reducing L. monocytogenes populations in most of the systems studied. PMID- 8368844 TI - Detection of hepatitis E virus in raw and treated wastewater with the polymerase chain reaction. AB - The main objective of this study was to determine the applicability of the polymerase chain reaction (PCR) to detection of hepatitis E virus (HEV) in sewage treatment plants and establishment of the prevalence of hepatitis viral diseases in a population. Epidemics of HEV infection because of inadequate public sanitation have been reported in several developing countries. A procedure for concentration of HEV in sewage samples through adsorption to membrane filters, elution with urea-arginine phosphate buffer, and subsequent reconcentration with magnesium chloride enabled us to concentrate HEV to volumes in the microliter range. HEV-specific cDNA was prepared by reverse transcription of the total RNA extracted from samples. Specific DNA amplification by PCR in combination with slot blot hybridization was used to demonstrate the presence of HEV in sewage samples from the inlets and outlets of three sewage treatment plants. The assay was specific for HEV, and a 240-bp amplified product was visualized by ethidium bromide fluorescence. Sewage samples adjusted to pH 5.0 for adsorption of viruses to membrane filters were PCR positive, while samples adjusted to pH 3.5 were PCR negative. PMID- 8368845 TI - Partial purification and characterization of mold antigens commonly found in foods. AB - Rapid methods are needed for detection of molds in foods; therefore, an enzyme linked immunosorbent assay was developed. The extracellular and mycelial antigens for Mucor, Aspergillus, Cladosporium, and Geotrichum species were partially purified and characterized. The molecular masses of the mycelial and extracellular antigens, as determined by size exclusion chromatography, ranged from 4.5 x 10(5) to 6.7 x 10(5) Da. There was only one main antigenic peak separated by Sepharose CL-4B and concanavalin A-Sepharose columns for Mucor, Cladosporium, and Geotrichum mycelial and extracellular antigens, but there were two for Aspergillus mycelial antigens and three for Aspergillus extracellular antigens. These antigens contained 10 to 50% protein which was part of the active site since protease digestion significantly decreased antigenic activity. Neutral sugars, ranging from 13 to 75%, made up the rest of the active site, and < 1% phosphate was detected in mycelial antigens. Geotrichum, Cladosporium, and Aspergillus antigens contained mainly glucose, galactose, and mannose. Mucor antigens contained these sugars plus fucose. The percentage of sugars differed between the mycelia and extracellular antigens. Enzymatic digestion and competitive inhibition tests using different sugar derivatives showed that galactosyl residues with beta linkages were immunodominant for Aspergillus, Geotrichum, and Cladosporium antigens and mannosyl residues with alpha linkages were immunodominant for Mucor antigens. PMID- 8368846 TI - Influence of temperature and relative humidity on the survival of Chlamydia pneumoniae in aerosols. AB - The survival of Chlamydia pneumoniae in aerosols was investigated by using a chamber with a capacity of 114.5 liters. We injected 5 x 10(7) inclusion-forming units (IFU) of C. pneumoniae in aerosols with a droplet size of 3 to 5 microns. Samples were taken after 30 s and every 1 min thereafter. The survival of C. pneumoniae was measured at four temperatures (8.5, 15, 25, and 35 degrees C) and at three different relative humidities (RH) of 5, 50, and 95% for each temperature. The survival rates of Streptococcus pneumoniae, Streptococcus faecalis, Klebsiella pneumoniae, Chlamydia trachomatis LGV2, and cytomegalovirus were also determined at 25 degrees C and 95% RH and compared with that of C. pneumoniae. At the mentioned temperatures and RH, a rapid decrease of C. pneumoniae IFU was observed in the first 30 s. After this the decrease in the number of IFU was more gradual. The survival of C. pneumoniae in aerosols were optimal at 15 to 25 degrees C and 95% RH; it was good compared with those of other microorganisms. A lower death rate was observed only in S. faecalis. In C. trachomatis, the death rate during the first 30 s was higher than that in C. pneumoniae (85 and 53.3%, respectively). After the first 30 s, the death rates in the two organisms were identical. It was concluded that transmission of C. pneumoniae via aerosols was possible. There is probably a direct transmission from person to person, taking into account the relatively short survival period of C. pneumoniae in aerosols. PMID- 8368847 TI - Lysine-mannitol-glycerol agar, a medium for the isolation of Salmonella spp., including S. typhi and atypical strains. AB - An agar medium for the isolation of Salmonella spp. is described. The medium, lysine-mannitol-glycerol agar, has features of both xylose-lysine-deoxycholate agar and mannitol-lysine-crystal violet-brilliant green agar, but glycerol is added for the differentiation of Salmonella and Citrobacter spp. The medium facilitates the detection of strains having atypical fermentation patterns, such as the lactose- or sucrose-positive salmonellae. The medium also detects Salmonella typhi after enrichment. PMID- 8368848 TI - Purification and characterization of a phenoloxidase (laccase) from the lignin degrading basidiomycete PM1 (CECT 2971). AB - A new lignin-degrading basidiomycete, strain PM1 (= CECT 2971), was isolated from the wastewater of a paper factory. The major ligninolytic activity detected in the basidiomycete PM1 culture supernatant was a phenoloxidase (laccase). This activity was produced constitutively in defined or complex media and appeared as two protein bands in native gel electrophoresis preparations. No enzyme induction was found after treatment with certain potential laccase inducers. Laccase I was purified to homogeneity by gel filtration chromatography, anion-exchange chromatography, and hydrophobicity chromatography. The enzyme is a monomeric glycoprotein containing 6.5% carbohydrate and having a molecular weight of 64,000. It has an isoelectric point of 3.6, it is stable in a pH range from 3 to 9, and its optimum pH is 4.5. The laccase optimal reaction temperature is 80 degrees C, the laccase is stable for 1 h at 60 degrees C, and its activity increases with temperature. Spectroscopic analysis revealed that the enzyme has four bound copper atoms, a type I copper, a type II copper, and a type III binuclear copper. The amino-terminal sequence of the protein is very similar to the amino-terminal sequences of laccases from Coriolus hirsutus and Phlebia radiata. PMID- 8368849 TI - Cellobiose versus glucose utilization by the ruminal bacterium Ruminococcus albus. AB - Cellulose degradation and metabolism in the rumen can be adversely affected by the presence of soluble sugars, but relatively little information is available on substrate preferences of cellulolytic bacteria. When the ruminal bacterium Ruminococcus albus was incubated with a combination of cellobiose and glucose, the organism preferentially utilized the disaccharide. This preference appeared to be related to repression of glucose uptake systems in cellobiose-grown cells. Glucose transport kinetics exhibited low- and high-affinity uptake, and high affinity transport was apparently driven by ATP hydrolysis. Bacterial yield in continuous culture was as much as 38% greater when the organism was grown on cellobiose versus glucose, and the increased yield could be partially attributed to constitutive cellobiose phosphorylase activity. The maintenance coefficient of glucose-grown cells was significantly greater than that of cells provided with cellobiose (0.225 g of glucose per g of protein per h versus 0.042 g of cellobiose per g of protein per h), and this result suggested that more energy was devoted to glucose uptake. Substrate affinities were examined in carbon excess continuous culture, and affinities for glucose and cellobiose were relatively low (0.97 and 3.16 mM, respectively). Although R. albus maintained a proton motive force of approximately 60 mV from pH 6.7 to 5.5, growth ceased below pH 6.0, and this inhibition of growth may have been caused by a depletion of ATP at low pH. PMID- 8368850 TI - Induction of folds or sutures on the walls of Cryptosporidium parvum oocysts and their importance as a diagnostic feature. AB - The proportion of oocysts of Cryptosporidium parvum showing a fold on oocyst walls when incubated with either fluorescent monoclonal antibody or a surface reactive fluorescent dye was increased by incubating suspensions of oocysts with dimethyl sulfoxide, sucrose, or Hanks' balanced salt solution. Further incubation of sucrose-incubated oocysts with water showed this to be a reversible phenomenon. Oocysts demonstrating this fold after incubation in dimethyl sulfoxide were of the same viability as control oocysts and followed the same excystation dynamics. Despite this fold having been previously described as a suture, we were unable to find any evidence that this pattern of fluorescence highlighted the same suture that has been described in ultrastructural studies. Furthermore, oocysts were observed in which this fold was not always continuous with the gape in the oocyst wall through which the sporozoites had emerged. We propose that this fluorescently highlighted region or fold should no longer be described as a suture and question its validity as a diagnostic feature. When environmental and other samples are being examined for the presence of C. parvum oocysts, objects of appropriate size, shape, and fluorescence which do not demonstrate a surface fold should not necessarily be excluded. PMID- 8368851 TI - Degradation of atrazine and 2,4-dichlorophenoxyacetic acid by mycorrhizal fungi at three nitrogen concentrations in vitro. AB - Nine mycorrhizal fungi and free-living saprophytic microorganisms were tested for their ability to degrade two chlorinated aromatic herbicides at two herbicide concentrations and three nitrogen concentrations. Radiolabelled 2,4 dichlorophenoxyacetic acid (2,4-D) and 2-chloro-4-ethylamino-6-isopropylamino-s triazine (atrazine) were used as substrates at concentrations of 1 and 4 mM. After 8 weeks, none of the cultures tested grew at 4 mM 2,4-D. However, when the 2,4-D concentration was reduced to 1 mM, Phanerochaete chrysosporium 1767 had the highest level of 2,4-D mineralization and degradation under all nitrogen conditions. All cultures tested grew at both atrazine concentrations. In all cases, the ericoid mycorrhizal fungus Hymenoscyphus ericae 1318 had the highest level of atrazine carbon incorporated into its tissue. In general, as the nitrogen concentration increased, the total herbicide degradation increased. All of the cultures, except for Rhizopogon vinicolor 7534 and Sclerogaster pacificus 9011, showed increased degradation at 4 mM compared with 1 mM atrazine. The ability to degrade these two herbicides thus appeared to be dependent on the fungus and the herbicide, with no correlation to fungal ecotype (mycorrhizal versus free living). PMID- 8368852 TI - Abundance of airborne Penicillium CFU in relation to urbanization in Mexico City. AB - Air was sampled simultaneously at three localities in Mexico City differing in urbanization index and air pollution level on 22 days during a period covering both dry and rainy seasons. An Andersen two-stage microbial sampler was used for 15 min at 28 liters min-1 to isolate culturable fungi on malt extract agar. After exposure, plates were incubated at 25 degrees C for 48 to 72 h before colonies were counted and identified to give concentrations of total fungal spores and of Penicillium spp., expressed as CFU per cubic meter of air. Total fungi numbered 91 to 602 CFU m-3 in Tlalpan Borough (southern area), 40 to 264 CFU m-3 in Cuauhtemoc Borough (downtown), and 26 to 495 CFU m-3 in Gustavo A. Madero Borough (northern area). Although Penicillium spp. were the second most frequently isolated fungal genus, concentrations were small, with a maximum of only 133 CFU m-3. Twice as many colonies were isolated in the southern area, with an urbanization index of 0.25 (arithmetic mean, 41 CFU m-3), as at other sampling stations with greater urbanization indices (arithmetic means, 19 and 20 CFU m-3). In the downtown area, with an urbanization index of 1.0, Penicillium spp. were more numerous than any other genus and formed 25% of the total fungal count compared with 14 and 17% in the other areas. Concentrations of airborne Penicillium spp. did not differ significantly between rainy and dry seasons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368853 TI - Production of [14C]fumonisin B1 by Fusarium moniliforme MRC 826 in corn cultures. AB - Kinetics of growth and fumonisin production by Fusarium moniliforme MRC 826 in corn "patty" cultures were investigated, and a technique was developed for the production of [14C]fumonisin B1 ([14C]FB1) by using L-[methyl-14C]methionine as the precursor. A significant (P < 0.01) correlation exists between fungal growth and FB1 (r = 0.89) and FB2 (r = 0.87) production in corn patties, beginning after 2 days and reaching the stationary phase after 14 days of incubation. [14C]FB1 was produced by adding L-[methyl-14C]methionine daily to cultures during the logarithmic phase of production. Incorporation of the isotope occurred at C-21 and C-22 of the fumonism molecule and was enhanced in the presence of unlabeled L methionine. Although the concentration of exogenous unlabeled methionine is critical for incorporation of the 14C label, optimum incorporation was achieved by adding 50 mg of unlabeled L-methionine and 200 mu Ci of L-[methyl 14C]methionine to a corn patty (30 g) over a period of 9 days, yielding [14C]FB1 with a specific activity of 36 mu Ci/mmol. PMID- 8368854 TI - A ribosomal DNA fragment of Listeria monocytogenes and its use as a genus specific probe in an aqueous-phase hybridization assay. AB - cDNAs were prepared from the total RNA of Listeria monocytogenes ATCC 19118 and used as probes to screen a genomic library of the same strain. Four clones were identified which contained ribosomal DNA fragments. Recombinant DNA from one of them was fractionated and differentially hybridized with the cDNA probes to RNA of L. monocytogenes and Kurthia zopfii. The resulting hybridization pattern revealed an HpaII fragment of 0.8 kb that was specific for the L. monocytogenes strain. The nucleotide sequence of this fragment showed 159 bases of the 3' end of the 16S rRNA gene, 243 bases of the spacer region, and 382 bases of the 5' end of the 23S rRNA gene. In dot blot hybridization assays, the 32P-labeled 784-bp fragment was specific only for Listeria species. Dot blot assays revealed that the 32P-labeled fragment can easily detect > or = 10 pg of total nucleic acids from pure cultures of L. monocytogenes, which corresponds to approximately 300 bacteria. This fragment was also used as a probe in an assay named the heteroduplex nucleic acid (HNA) enzyme-linked immunosorbent assay. In this system, the biotinylated DNA probe is hybridized in the aqueous phase with target RNA molecules and then specific HNAs are captured by HNA-specific antibodies. Captured HNA molecules are revealed with an enzyme conjugate of streptavidin. In a preliminary HNA enzyme-linked immunosorbent assay, the 784-bp fragment maintained its specificity for Listeria spp. and could detect 5 x 10(2) cells in artificially contaminated meat homogenate. PMID- 8368855 TI - Microbial degradation of chlorinated acetophenones. AB - A defined mixed culture, consisting of an Arthrobacter sp. and a Micrococcus sp. and able to grow with 4-chloroacetophenone as a sole source of carbon and energy, was isolated. 4-Chlorophenyl acetate, 4-chlorophenol, and 4-chlorocatechol were identified as metabolites through comparison of retention times and UV spectra with those of standard substances. The proposed pathway was further confirmed by investigation of enzymes. The roles of the two collaborating strains were studied by growth experiments and on the level of enzymes. If transient accumulation of 4 chlorophenol was avoided either by the use of phenol-absorbing substances or by careful supplement of 4-chloroacetophenone, the Arthrobacter sp. was able to grow as a pure culture with 4-chloroacetophenone as a sole source of carbon and energy. Several mono-, di-, and trichlorinated acetophenones were mineralized by the Arthrobacter sp. PMID- 8368856 TI - Monoclonal antibodies that react with live Listeria spp. AB - Seven monoclonal antibodies (MAbs) against Listeria spp. that were reactive with live Listeria spp. were developed. Two of these MAbs (55-8 and 55-37) were members of the immunoglobulin M class, and all other MAbs were members of the immunoglobulin G class. MAb 55-23 reacted with 148 of 157 strains tested. MAb 34 51 reacted with serotype 1/2a, 1/2b, and 1/2c strains and exhibited a scattered reaction pattern with strains belonging to other serotypes. MAb 55-44 reacted with all of the strains belonging to serotype 4b tested. MAb 55-4 reacted with all of the serotype 1/2a isolates tested, although reactivity with other isolates also was observed. The other MAbs exhibited scattered reaction patterns. No correlation of reactivity pattern with serotype was found. Marked differences were observed between the reactivities of MAbs as determined by a magnetic immunoluminescence assay and a whole-cell enzyme-linked immunosorbent assay. Only MAb 55-23 exhibited minor reactivity with three Streptococcus spp. isolates, while no reactivity was observed with six Bacillus spp. strains, one Escherichia coli strain, and one Citrobacter sp. strain. In Western blots (immunoblots) MAbs 55-23, 55-44, and 34-9 exhibited reactivity; all other MAbs were negative in this assay. PMID- 8368858 TI - Use of vaginal tampons in sewer surveys for non-O1. Vibrio cholerae. AB - Vaginal tampons were shown to be a practical alternative to conventional Moore swabs for isolating Vibrio cholerae from sewage. Associated laboratory investigations demonstrated improved isolation of V. cholerae by using 12- or 18 h enrichments in alkaline peptone water, in comparison with 6-h enrichments, when cultures were incubated at ambient temperatures. PMID- 8368857 TI - Identification of a high-affinity glycine betaine transport system in Staphylococcus aureus. AB - Staphylococcus aureus accumulates proline and glycine betaine when cells are grown at low water activity. In the present study, we have identified a high affinity glycine betaine transport system in this bacterium. Optimal activity for this transport system was measured in the presence of high NaCl concentrations, but transport activity was not stimulated by high concentrations of other solutes. PMID- 8368859 TI - Detection of Listeria monocytogenes with a nonisotopic polymerase chain reaction coupled ligase chain reaction assay. AB - A polymerase chain reaction (PCR)-coupled ligase chain reaction (LCR) assay for the specific detection of Listeria monocytogenes (M. Wiedmann, J. Czajka, F. Barany, and C. A. Batt, Appl. Environ. Microbiol. 58:3443-3447, 1992) has been modified for detection of the LCR products with a nonisotopic readout. When a chemiluminescent or a colorimetric substrate for the nonisotopic detection of the LCR products was used, the PCR-coupled LCR gave a sensitivity of 10 CFU of L. monocytogenes. The detection method with the chemiluminescent substrate Lumi-Phos 530 permitted detection of the LCR products in less than 3 h, so that the whole assay can be completed within 10 h. PMID- 8368860 TI - Evaluation of indoxyl-beta-D-glucuronide as a chromogen in media specific for Escherichia coli. AB - Indoxyl-beta-D-glucuronide (indoxyl) was evaluated as a specific chromogen for detection of Escherichia coli by the membrane filter method. In all, 413 colonies were tested from the indoxyl-supplemented media, yielding 93.3% confirmation, as E. coli. Compared with the indoxyl medium, other media gave either much lower recovery with high verification or equal recovery with poor verification. PMID- 8368861 TI - Starved cells of the fatty acid auxotroph Escherichia coli AK7 develop abnormal sensitivity to media with low osmolarity. AB - The unsaturated fatty acid auxotroph Escherichia coli AK7 supplied with linolenic acid, while appearing normal during logarithmic growth, showed a fast decline in CFU during starvation as a result of an osmotic downshift when transferred to standard agar plates unsupplemented with an osmolyte such as 300 mosM sucrose or salt (NaCl or KCl). The starved cells could recover their osmoresistance when an energy source was added to the starvation medium. PMID- 8368862 TI - Effect of substrate composition on intestinal flora. PMID- 8368863 TI - The carbamate insecticide ZZ-Aphox induced structural changes of gills, liver, gall-bladder, heart, and notochord of Rana perezi tadpoles. AB - Embryos of Rana perezi were kept under laboratory conditions and treated with carbamate ZZ-Aphox at chronic doses of 0.02% and 0.14% for 9 weeks. Both the histological study and the analysis of mortality show a direct relationship between the dosage and the effects of the pesticide. The histological study of the survivors over 56 days show damages in gills, liver, gall-bladder, heart, and notochord. Damages on the epithelial of gills (on their distal portion) and gall bladder recover over a few days, whereas those provoked on the compacting of the hepatic parenchyma and the hepatocytes, the auricle and the perintocohordal collagenic fibers alter their structure in a lasting way. Potentials of such alterations are discussed, with special reference to the possible interference of the pesticide on the successful synthesis of the supporting connective sheaths. PMID- 8368864 TI - Effects of 2,4-dichlorophenoxyacetic acid butyl ester on chick liver. AB - Fertilized hen eggs were externally treated with 3.1 mg 2,4-dichlorophenoxyacetic acid butyl ester (2,4-D ester) before starting incubation. Liver lipid composition, (14C)2,4-dichlorophenoxyacetic acid (14C-2,4-D) subcellular distribution and covalent binding to proteins and lipids of chicks hatched from these eggs were studied. Furthermore, catalase, glutathione S-transferase and glucose 6-phosphatase activities as well as reduced glutathione content were determined. The herbicide produced a significant decrease on the total lipids, specially on phospholipids, both in total liver and microsomes. (14C-2,4-D) subcellular distribution in liver demonstrated that the herbicide passed through the plasmatic membrane and it was present in all the studied fractions. Herbicide bound covalently to hepatic proteins and lipids, being the binding to proteins tenfold higher than to lipids. Because these results might be of potential relevance to the understanding of the 2,4-D toxicity, further studies on the mechanisms of these reactions are necessary. On the other hand, the microsomal and cytosolic glutathione S-transferases activities remained unchanged, even though in vitro studies 2,4-D ester caused a decrease of the enzyme activities with an I50 value of 0.2 mM. No significant change in reduced glutathione content between control and treated livers was observed. The catalase activity increased two-fold whereas glucose 6-phosphatase activity decreased 46% with respect to the corresponding control values. These results indicate that 2,4-D ester may have effects on the metabolism of xenobiotics. PMID- 8368865 TI - Isomer-specific analysis and toxic evaluation of polychlorinated biphenyls in striped dolphins affected by an epizootic in the western Mediterranean sea. AB - Isomer-specific concentrations of polychlorinated biphenyls (PCBs) including planar, mono- and di-ortho congeners and concentrations of DDT were determined in striped dolphins affected by a morbillivirus epizootic in the western Mediterranean in 1990. Extremely high concentrations of PCBs ranging from 94 to 670 micrograms/g (wet wt) were detected in the blubber. Similarly, DDT concentrations were high, between 22 and 230 micrograms/g (wet wt). The concentrations of three non-ortho coplanar PCBs were 43 (3,3',4,4'-T4CB), 6.8 (3,3',4,4',5-P5CB), and 7.8 (3,3',4,4',5,5'-H6CB) ng/g (wet wt), respectively, the highest residue levels reported to date. The estimated 2,3,7,8-TCDD toxic equivalents of non-, mono- and di-ortho PCB congeners in striped dolphins were several times higher than those observed for other marine mammals and humans. Mono-ortho congeners contributed greater 2,3,7,8-TCDD toxic equivalents than non ortho members. The higher ratio of 3,3',4,4',5,5'-H6CB/3,3',4,4',5-P5CB (IUPAC 169/126) suggested a strong induction of mixed function oxidase enzymes and highlighted the possibility of using this ratio as an index for risk assessment of PCB contamination in marine mammals. Elevated concentrations of PCBs may have played a role in the immune depression in striped dolphins, ultimately leading to the development of morbillivirus disease. PMID- 8368866 TI - A comparison of microbial bioassays for the detection of metal toxicity. AB - Heavy metal toxicity was studied by assaying six microbiological toxicity tests, both in solution and wastewater. Pseudomonas fluorescens and baker's yeast (Saccharomyces cerevisiae) were used; growth and respirometric determinations were performed. In addition, the Microtox test was employed as a reference method. The Microtox test is the most sensitive assay for detecting toxicity of zinc, copper, and mercury but not for cadmium, chromium, and nickel. Wastewater increases the sensitivity threshold (EC20) and EC50 values of the metals in most of the assays, which is correlated to the presence of organic and inorganic compounds that can reduce the bioavailability of the metals, leading to a general loss of sensitivity. All the above-mentioned assays are potentially useful in the detection of chemical toxicity of metals. However, each test shows different sensitivities to each metal, which is related to different sensitivities of the organisms used in the assays, as well as to other factors. Therefore, it would be advisable to use a battery of tests for biological evaluation of metal toxicity. PMID- 8368868 TI - Chemically-induced histone modification as a predictor of carcinogenicity. AB - The interaction between carcinogens and DNA is believed to initiate neoplastic transformation, but evidence suggests that epigenetic mechanisms may also be of importance. Because the histone proteins have important roles in chromatin structure and cellular function, they provide a reasonably well understood epigenetically-based system for the detection of carcinogens. In this study, human foreskin fibroblastic cells were exposed to one of several mutagens and/or carcinogens for 3, 12, or 24 h to determine if induced histone modification may be a means of predicting chemical carcinogenicity. Butyric acid (5 mM), known to result in acetylation of histones H3 and H4, and 12-O-tetradecanoylphorbol-13 acetate (3 microM), known to result in phosphorylated histone H1, were tested initially. Electrophoresis of the histone fractions was capable of resolving multiple forms of histones H1, H3, and H4. Propane sultone (0.1 mM) induced a broadening of the H2A and H2B bands after a 24 h exposure and carbon tetrachloride (1 mM) induced the formation of new histone forms in the H1 fraction after 24 h and in the H3 fraction after 3 h. Experimental variability limited the statistically significant modifications to carbon tetrachloride and propane sultone, two known carcinogens, where new forms of modified histone were detected. Therefore, the histone modification assay, with further experimentation, may be an alternate method of detecting carcinogens, especially when conventional genotoxic tests prove unreliable. PMID- 8368867 TI - Effect of side-stream cigarette smoke on the hepatic cytochrome P450. AB - The effect of inhalation of side-stream cigarette smoke on the hepatic microsomal cytochrome P450 was investigated Rats were placed in a chamber of 0.1 m3 in volume, in which cigarettes were burned at the rate of 1, 3, or 5 cigarettes per h, 8 h/day for 5 days. Cytochrome P450 and NADPH-cytochrome c reductase showed no significant changes; however, cytochrome b5 increased significantly. On the other hand, the activity of aryl hydrocarbon hydroxylase (AHH) decreased in the rats treated with a high concentration of cigarette smoke. In order to study the changes of isoforms of cytochrome P450, western blot analyses were performed. The inductions of three kinds of isoforms, cytochromes P450IA1, IA2, and IIB1, were demonstrated immunochemically. However, there were disagreements between the results of the western blot analyses and the measurements of total cytochrome P450 content and AHH activity. PMID- 8368869 TI - Effects of patulin on postimplantation rat embryos. AB - Patulin (PAT), a highly toxic, carcinogenic, heterocyclic lactone is produced by a variety of fungal species, including Penicillium and Aspergillus. This compound has been isolated from various apple products and is stable in apple and grape juice and dry corn. It has been reported to be cytotoxic and to exert adverse influence on development in vivo in mice and merits further study and evaluation. In this study, whole rate embryo culture (WEC) was used to determine the teratogenic potential of PAT in vitro. Embryos were exposed to PAT-treated (0.00 62 microM) rat serum for 45 h. The embryos that were exposed to 62 microM PAT were not evaluated because they did not survive beyond 40 h of incubation. The results indicate that PAT induced a statistically significant reduction in protein and DNA content, yolk sac diameter, crown rump length, and somite number count. Patulin treatment also resulted in an increase in the frequency of defective embryos. Anomalies included growth retardation, hypoplasia of the mesencephalon and telencephalon, and hyperplasia and/or blisters of the mandibular process. Thus, the data from the present study provide further evidence supporting the conclusion that the whole rat embryo assay is a rapid and sensitive in vitro method that can be employed to pre-screen developmentally toxic mycotoxins. PMID- 8368870 TI - Effects of pesticides on isolated rat hepatocytes, mitochondria, and microsomes. AB - Twenty-seven pesticides, with which people are concerned, especially as residues in food, were examined in vitro for their effects on hepatocytes, mitochondria, and microsomes isolated from male rats. Nineteen pesticides returned non-protein sulfhydryl (NPSH) contents in hepatocytes to less than 80% of control at concentrations from 10(-3) to 10(-5) M after 90 min incubation. Among them, only dichlofluanid was reactive with glutathione non-enzymatically. Lipid peroxidation in hepatocytes was stimulated by five pesticides at 10(-3) M, with edifenphos being the most potent peroxidant. Cell viability was considerably decreased by incubation with chlorobenzilate, edifenphos, dichlofluanid, and chinomethionat at 10(-3) M, and in these cases, depletion of cellular adenosine 5'-triphosphate (ATP) contents proceeded to cell death. With respect to isolated mitochondrial respiration, six pesticides inhibited state 3 and/or state 4 respiration rates at concentrations from 10(-3) to 10(-5) M, whereas three pesticides uncoupled state 4 respiration at 10(-3) M. With respect to isolated microsomal lipid peroxidation, seven pesticides, five of which were organophosphorus compounds, were peroxidative at concentrations from 10(-3) to 10(-5) M, whereas seven pesticides were antioxidative at concentrations from 10(-3) to 10(-7) M. Only three pesticides, aldicarb, maleic hydrazide, and chlormequat chloride had no effect on any parameters tested at 10(-3) M. Pesticides that affected isolated mitochondria or microsomes did not necessarily have any effect on isolated hepatocytes. PMID- 8368872 TI - Effect of nitrogen limitation on the biodegradability and toxicity of nitro- and aminophenol isomers to methanogenesis. AB - Monosubstituted nitro- and aminophenol isomers exhibited limited biodegradability under methanogenic conditions when supplied as the sole source of carbon and energy. This was examined by supplying to the same sediment samples, each isomer of nitro- and aminophenol as a sole source of added carbon under either N supplemented or N-deprived methanogenic conditions. The results demonstrated that under N-supplemented conditions, only 2-NP (NP = nitrophenol), 4-NP and 4-AP (AP = aminophenol) were stoichiometrically mineralized, 2-AP, 3-AP, and the 3-AP metabolite formed from 3-NP reduction were persistent over the 51-week incubation period. In addition, NP isomers inhibited initial rates of methanogenesis, while all AP amended cultures exhibited no significant inhibition in the rate of methanogenesis. Under N-deprived conditions, 2-NP, 2-AP and 4-AP were mineralized, while 3-NP, 4-NP and 3-AP were persistent over the 51-week incubation period. Although all NP isomers were still metabolized through the corresponding AP isomer, the deprivation of nitrogen significantly depressed both the rate and extent of methanogenesis. In general, nitrogen supplemented cultures produced 25% more methane than the nitrogen limited cultures, and the initial rates of methanogenesis were four times greater. While these data showed that under N-deprived conditions methanogenesis was inhibited to a greater extent by these compounds, it also suggests that N-deprived conditions may have facilitated the establishment of a 2-AP metabolizing consortium. PMID- 8368873 TI - In this year of health care reform, nurses' voices must be heard! PMID- 8368871 TI - Frictional transition of pesticides from protective clothing. AB - Frictional transition of pesticides, the transition of the dried pesticide due to rubbing, from protective clothing was investigated by using an AATCC standard crockmeter. One insecticide (carbaryl) and two herbicides (atrazine and metolachlor) were studied, together with three protective clothing materials [cotton, polyester, and polyester/cotton (65/35) blend] and three crock fabrics (cotton, nylon, and silk). The effects of the properties of pesticide, fabrics, water, and perspiration on the frictional transition are discussed. The experiment showed that up to 12% of the pesticide could transfer from contaminated protective clothing to the skin through rubbing. Choosing the right materials for protective clothing and underwear would greatly decrease the frictional transition of the pesticide. PMID- 8368874 TI - An open letter to Hillary Rodham-Clinton regarding health care reform. PMID- 8368875 TI - President's message. Keeping an eye on the Clinton health care reform plan. PMID- 8368876 TI - An evaluation of the nephrology nursing research literature: 1979-1989. AB - The purposes of this project were: to describe the research designs, areas of study, and major dependent variables of nephrology nursing research conducted between 1979 and 1989; and to evaluate the quality of this research. Of the 284 publications included, 34.9% of the research designs were descriptive; 45.4% analytical observational; 4.9% methodological; 14.1% experimental; and 0.7% historical. Content analysis was conducted to classify the area of study and dependent variables. Nurse experts assessed the quality of the research studies using Georgopoulos' (1975) Quality Index. PMID- 8368877 TI - Renal physiology series: Part 5b of 8. Renal control of phosphorus and magnesium. AB - The kidney plays a major role in the maintenance of phosphorus and magnesium balance. The homeostasis of these substances is complex and also involves the gastrointestinal tract and the bone. This article reviews the functions, homeostasis, and renal handling and regulation of phosphorus and magnesium. The major sites of tubular reabsorption and the presumed cellular mechanisms involved are described. PMID- 8368878 TI - Quality of life in elderly renovascular hypertensive patients. AB - This study assessed perceived quality of life in elderly, surgically managed renovascular hypertension patients. Twenty-three patients, aged 55 to 90 years, with unilateral or bilateral aortorenal bypass grafting or transrenal or transaortic endarterectomy, participated in the study. The Sickness Impact Profile was used to measure perceived quality of life. Overall, elderly, renovascular hypertension patients, at least 1 year postoperatively, experienced quality of life comparable to persons with other serious chronic illnesses; and females reported significantly poorer quality of life than males. PMID- 8368879 TI - The influence of physical activity on fatigue in patients with ESRD on hemodialysis. AB - This study examined the relative influence of anemia, nonspecific symptoms and physical activity on fatigue in 43 patients with end stage renal disease on chronic hemodialysis. We found that low levels of physical activity and frequent symptoms were related to high levels of fatigue. Degree of anemia was not related to level of fatigue. Inactivity contributed to fatigue scores more than symptoms. PMID- 8368880 TI - Research series: Part 4 of 6. Annotated bibliography: instrument references, instrumentation, reliability and validity. PMID- 8368881 TI - Case management of the anemic patient: epoetin alfa--focus on compliance. AB - Lack of compliance with a treatment regimen is a common problem in patients with ESRD and can mean that a patient fails to receive the full benefit from therapies, including Epoetin alfa. Nurses can, through careful assessment and intervention, work with patients to encourage compliance. Viewing compliance as a partnership between nurse and patient and using strategies such as joint decision making can facilitate this process. PMID- 8368882 TI - 1993 educational resource directory. PMID- 8368883 TI - Pediatric case study: hemolytic uremic syndrome. AB - The nursing interventions necessary to care for this critically ill child were professionally challenging. Meeting the psychosocial, educational, and supportive needs of the family during this period of uncertainty, as well as, providing the dialysis therapy and support for this fragile child demonstrated the unique contributions of professional nursing. All outcomes were met, but the patient's extremely poor myocardial function made dialysis treatments and volume control difficult. The use of CVVHD was instrumental to providing dialysis in a safe, effective manner. The nursing care for S.B.K. and her family was physically and emotionally draining, but seeing her neurological status return was the great reward for all of our efforts. PMID- 8368884 TI - What is hepatitis C? PMID- 8368885 TI - Nursing guidelines for cyclosporine. PMID- 8368886 TI - Documentation using the Roy Adaptation Model. PMID- 8368887 TI - Karyotype polymorphism and conserved characters in the Leishmania (Viannia) braziliensis complex explored with chromosome-derived probes. AB - Molecular karyotype of 45 reference populations of Neotropical leishmanias was analyzed with ethidium bromide staining and with 6 chromosome-derived probes selected from a genomic library of Leishmania (Viannia) braziliensis. Size conserved patterns were identified and found to be specific to subgenus Viannia and to its constitutive species. An important issue for epidemiology and clinical investigations was the discrimination between L. (V.) peruviana and L. (V.) braziliensis, 2 species found very similar by other genetic techniques, but responsible for totally different clinical patterns. The suggested existence of genetically distinct demes, or karyodemes, within the group-species might also show to be of importance, as these populations might differ in virulence, host specificity and clinical manifestations. PMID- 8368888 TI - [Factors affecting the efficacy of 2 growth regulator compounds, OMS 3010 (phenoxycarb) and OMS 3019 (ethoxypyridine), on larvae of the Simulium damnosum complex]. AB - Two insect growth regulators (IGR'S) acting as juvenile hormone analogs (JHA'S), OMS 3010 (phenoxycarb) and OMS 3019 (ethoxypyridine) were selected after a screening of several compounds proposed by industry on black fly larvae of the Simulium damnosum complex (Diptera: Simuliidae) the vector of onchocerciasis in West Africa. Bioassays were designed to study two parameters: larval age and exposure time. The results showed that these compounds are more efficient on old larvae (6th and 7th instars) than young larvae (3rd, 4th and 5th instars). However, exposure time seems essential. The black fly larvae live in fast running water courses. Thus, it is difficult to insure a prolonged exposure time in natural conditions. Though being active on black fly larvae, three factors are limiting the prospects for operational use of these two compounds: high dosages, limited effectiveness on young instar larvae and exposure time. PMID- 8368889 TI - [Geographic distribution of HIV-1 infection in Central Africa: remarkable discontinuities]. AB - The (confirmed) serological data, collected since 1985 and spread in space and in time, allow to draw a geographical image--distribution, dissemination--of HIV 1 infection. These data raise some questions and hypotheses on the nature and the dynamics of the epidemiological factors involved. The geographical distribution of the infection in the global population is heterogeneous. Ever since the first surveys, the virus is widely spread at low level, in the rural as well as in the urban areas, covering a large territory, from Chad to Gabon; later it tends to focus on the large metropolitan and secondary towns. The endemicity is more pronounced in a double urban conglomerate (Kinshasa, Brazzaville) and in two regional foci, the southwest of the Congo and the south of Shaba; in the two towns the prevalence rate does not progress between 1985-86 and 1991-92. The Central African Republic has suffered an active epidemic outbreak, affecting the capital and the whole network of secondary towns. The epidemiological discontinuities noticeable across Central Africa, may represent different stages of the same process or be connected to the stake of different eco-epidemiological systems. PMID- 8368890 TI - Introduction of HIV-1 in a rural city of Zaire. AB - In the rural city of Inongo (Bandundu region, Zaire), the prevalence of HIV-1 infection has been investigated during a survey on HTLV-I infection and associated neurological diseases, using a cluster sampling technique. Thirteen individuals were infected by HIV-1, 11 adults and 2 children, giving a crude prevalence rate in the cluster sample of 1.1%. More women were infected than men. After direct standardization on the age and sex structure given by the 1984 census, the prevalence of HIV-1 in the city may be estimated at 1.0% for the whole population and 1.6% for the population above 15 years of age. The importance is stressed of protecting rural populations, particularly women of childbearing age from the HIV epidemic, by information campaigns focused on the male migrant population, including both seasonal and travelling workers. PMID- 8368891 TI - Further African cases of rhinosporidiosis. AB - Thirteen African cases of rhinosporidiosis are reported from Burundi, Rwanda, Tanzania, Chad and Zaire. They include the first reported cases from Burundi and from Rwanda and the first African case, outside nose and eye, localized on the urethral orifice in a Zairian male. PMID- 8368892 TI - [Morbidity and mortality related to obstetrical referral patients to the hospital of Bobo-Dioulasso, Burkina Faso]. AB - The obstetrical referral patients admitted to the Sanon Souro hospital in Bobo Dioulasso (Burkina Faso) during 1991 were retrospectively reviewed. During the study period 741 women were admitted. The median distance between the referring centre and Bobo-Dioulasso was 33 km. Median age was 22 years and median parity was 3. Indications for referral were dominated by obstructed labour, haemorrhages and infections. The proportion of maternal mortality in the study was 5.4% and was not related to maternal age or parity. However, there was a linear trend of increasing mortality according to the distance between the referring centre and Bobo-Dioulasso (X2 for trend: 7.56; p = 0.006). The perinatal mortality rate of 420 p. thousand was not related to maternal age, but a parity exceeding 4 was a risk factor for the occurrence of perinatal death (relative risk: 1.4; 95% C.I.: 1.2-1.7). As for maternal mortality, there was a linear increase of perinatal mortality with the distance from the referring centre (X2: 20.8; p = 0.00001). There was no marked seasonal variation in the number of referrals nor in the mortality rates per month. PMID- 8368893 TI - [Risk approach in the diagnosis of malaria in high altitude regions]. AB - Sixteen cases of malaria are reported per thousand inhabitants per year in Kayanza, a province in the High Plateaux of Burundi. A case control study was conducted between October 1990 and March 1991 to better document this phenomenon. The majority of confirmed cases presented in persons who had recently sojourned in an endemic area (relative risk = 18). All except one of the other patients were carriers of plasmodium species that can cause late recurrences, which is compatible with the absence of local transmission. The presumptive diagnosis of malaria, as it is routinely made in the health centres, is not very specific (60%) and it has a positive predictive value of only 10%. This implies that an anti-malaria treatment is useless for 90% of the patients who receive it. It also means that the true malaria incidence rate in Kayanza can be estimated at less than 1 per thousand per year. We propose an alternative diagnostic strategy based on the risk differences between population sub-groups. It should permit an adequate patient management and a satisfactory surveillance of malaria in non endemic epidemiological strata. PMID- 8368894 TI - [Antimalarial measures in expatriates in the Congo. Trends 1989-1992]. AB - The modalities of prevention and treatment of malaria in expatriates residing in Brazzaville, capital of the Congo, have been studied in March 1989, April 1990 and April 1992. These surveys of the type Behavior, Attitude, Practice have been carried out in the Ecole Francaise where the same questionnaire has been distributed among the primary school children to complete by their parents. Only the data pertaining to Europeans, Lebanese, and North-Americans are presented. The proportion of French expatriates is 80%. A progressive decrease is noticed in the regular taking of chemoprophylaxis: the percentage varies between 86 and 43% according ot the duration of residence in 1989, to between 57 and 16% in 1992. Chloroquine alone remains the most widely used product, especially in long term expatriates. The association chloroquine-proguanil is mentioned only by a quarter or respondents. Apparently efficient, it is especially taken by people exposed for less than 4 years. Amodiaquine, although contra-indicated for prevention purposes, is cited in 1992 by 9% of subjects taking regular chemoprophylaxis; other products are only exceptionally used. In curative treatment, which generally is presumptive, halofantrine is since 1990 the most widely used drug, especially in children. In contrast, a relative disclaimer is noted for the amino 4-quinolines, due to resistance, but also and with no justification, for the association sulfadoxine-pyrimethamine and, to a lesser degree, for quinine. The occurrence of attacks considered to be malarial and their frequency, remained stable during the period of study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368895 TI - Factors affecting incidence and quality of autopsies. PMID- 8368896 TI - College of American Pathologists position statement regarding rapid detection of Mycobacterium tuberculosis. PMID- 8368897 TI - The epidemiology of latex allergy in health care workers. PMID- 8368898 TI - Current status of mycobacterial testing in clinical laboratories. Results of a questionnaire completed by participants in the College of American Pathologists Mycobacteriology E survey. AB - To learn what methods are used in clinical microbiology laboratories for detection, identification, and susceptibility testing of mycobacteria, questions addressing these issues were added to the College of American Pathologists' Mycobacteriology E proficiency testing survey, and participants in the survey were asked to complete the questionnaire. Other questions related to numbers of mycobacteriology tests performed and the frequency with which drug-resistant Mycobacterium tuberculosis is isolated. Just over half of the respondents stained smears for acid-fast bacilli with the fluorochrome stain. Only 26% of respondents processed respiratory specimens daily, potentially providing results within 24 hours of receiving the specimen. The most rapid methods currently available for detection of mycobacteria and for identification of M tuberculosis, respectively, were used by 30% and 35% of the respondents. Half of the respondents who performed susceptibility testing on isolates of M tuberculosis used rapid methods. Approximately 26% of the respondents indicated that they usually provided a final identification of M tuberculosis within 21 days of receiving a specimen, and 11% indicated that identification and susceptibility test results were reported within 28 days. Participants' responses indicated that the mean number of specimens received for mycobacterial culture per month was higher during the first 5 months of 1992 than it had been in 1991. Moreover, the number of drug-resistant M tuberculosis isolated per month from January through May 1992 was about double the number isolated per month in 1991.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368899 TI - Reference values and participant means as targets in proficiency testing. AB - Regulatory agencies will be placing greater reliance on the results of proficiency testing (PT) for determining licensing status of individual laboratories. This has caused a renewed interest in the process used by proficiency test providers for determining the correct result for each proficiency test challenge. Three general techniques have been proposed and would be allowed under the regulations: (1) participant-derived targets (means from a specific group of participants); (2) targets from a set of "reference" laboratories, from either a subset of participants or a selected group of experts using a rigorous experimental protocol; or (3) definitive values from a single source. The College of American Pathologists (CAP) has used all three techniques at different stages and for different purposes in the history of the CAP Surveys programs. This article reviews the early experiences of the CAP, the evolution of the current protocol, and activities to monitor the accuracy of target values. Participant-derived "consensus" results have been shown to be highly accurate and reliable. The CAP uses definitive methods at the National Institute for Standards and Technology and certified reference materials to monitor the validity of targets used in proficiency testing. PMID- 8368901 TI - The prevalence of atopy and hypersensitivity to latex in medical laboratory technologists. AB - Members of the Alberta Society of Medical Laboratory Technologists were invited to take part in a study of sensitivity to latex gloves. A total of 230 persons volunteered; 108 (47%) had no problems with gloves, and 122 (53%) reacted to latex gloves. A history was obtained regarding atopy, smoking, years in laboratory medicine, and the nature of the problem with latex gloves. Serum was assayed for the total IgE level and the presence of IgE with specificity to common inhalant allergens and to latex. The affected group had an increased population of subjects with an atopic history and a higher incidence of a raised IgE level and a positive screen for inhalant allergens. In the affected group, there was no relationship between the total IgE level and severity of skin reaction. However, smoking was related to severity of reaction and was more common in the groups with a more severe reaction. Three subjects were positive for IgE specific for latex; there were no other data distinguishing them from latex-negative subjects. PMID- 8368900 TI - The significance of ionized calcium in cardiac and critical care. Availability and critical limits at US medical centers and children's hospitals. AB - The clinical use of ionized calcium has increased since the recognition of its importance in cardiac and critical care medicine. However, more than half the general medical centers in the United States do not provide immediate testing of ionized calcium levels in patients in critical care settings, although indications for this test indicate that they should. The following objectives were used in this study: (1) to determine the availability of ionized calcium testing; (2) to document appropriate critical limits; and (3) to describe the significance of ionized hypocalcemia in cardiac and critical care. The participants were 100 medical centers and 40 children's hospitals in the United States. At medical centers, mean (+/- SD) critical limits were as follows: low, 0.82 +/- 0.14 mmol/L (3.29 +/- 0.56 mg/dL); and high, 1.55 +/- 0.19 mmol/L (6.21 +/- 0.76 mg/dL). At children's hospitals, mean critical limits were as follows: low, 0.85 +/- 0.13 mmol/L (3.41 +/- 0.52 mg/dL); and high, 1.53 +/- 0.11 mmol/L (6.13 +/- 0.44 mg/dL). In the past decade, the availability of ionized calcium testing increased dramatically. Now, 57%, 86%, 95%, and 100% of general hospitals, heart transplant centers, children's hospitals, and pediatric heart transplant centers, respectively, perform testing in house. Collective experience indicates that: (1) aggressive monitoring of ionized calcium prevents cardiac (and neurologic) catastrophes, (2) appropriate levels optimize cardiac function, and (3) calcium repletion is safest when based on acute trends measured directly in whole blood. Hospitals should provide rapid response testing needed during transplantation and massive transfusion and for the diagnosis and treatment of acute ionized hypocalcemia. PMID- 8368902 TI - Computers in total quality management. Statistical process control to expedite stats. AB - We developed a system of computer programs to gather and then display data on turnaround time for stat tests. The data were those generated by the testing process itself so that no additional data entry was necessary. The system provided daily as well as longitudinal data for statistical process control implemented in the laboratory. The median and 90th percentile turnaround times were calculated for high-volume tests (complete blood cell count and Chem6 [six chemical serum component concentrations, ie, sodium, potassium, chloride, carbon dioxide, glucose, and urea nitrogen]), and a graphic display was automatically generated. These parameters and visual aids permitted evaluation of stat processing in the laboratory. The impact of management decisions on the stat process could be measured. Intralaboratory processing procedures were modified, and phlebotomy personnel were repositioned. Our various measurements showed which decisions improved stat turnaround time. PMID- 8368903 TI - Aggressive angiomyxoma in men. A report of two cases associated with inguinal hernias. AB - Aggressive angiomyxoma is a rare, locally invasive, but nonmetastasizing soft tissue tumor that most commonly occurs in the pelvis or perineum of premenopausal women. In this article, we report two cases of aggressive angiomyxoma that occurred in middle-aged men. Although both patients initially presented with inguinal hernias, in other respects the two cases were significantly different. In one case, the tumor was small and found only incidentally at the time of surgery. In the other case, the tumor was extremely large, primarily involved the scrotal soft tissue, and was clinically thought to represent a testicular tumor. PMID- 8368904 TI - Laryngeal chondrosarcomas. AB - Four cases of laryngeal chondrosarcoma are presented. The patients' ages ranged from 60 to 75 years; one was a man and three were women. Two of the tumors arose in the thyroid cartilage, one in the cricoid cartilage, and one in the left arytenoid cartilage. A rapid fatal course with pulmonary and cerebral metastases was observed for the tumor arising in the arytenoid cartilage that histologically corresponded to a myxoid chondrosarcoma. The other three cases corresponded to low-grade, well-differentiated chondrosarcomas of the hyaline type, and the patients were alive and free of recurrence or metastases 3 to 6 years following total and partial laryngectomy. A review of the literature on the topic and the importance of assessing histologic grade, size, and location in the evaluation of these neoplasms is discussed. PMID- 8368905 TI - Intracranial lipomas with teratomatous elements. AB - We report two cases of patients with intracranial tumors that share features with lipomas and teratomas. Although rare reports of lipomas with "hypertrophic nerves" and "teratoid tumors" have been recorded, these two cases are unusual because they contain mature neuroectoderm (choroid plexus, peripheral nerve) and mesoderm (skeletal muscle). The findings are discussed and modern classification schemes are presented. We believe that the cases are examples of a transition between lipoma and teratoma. PMID- 8368906 TI - Inflammatory pseudotumor of the spleen. A clinicopathologic and immunophenotypic study of eight cases. AB - We report the clinical, pathologic, and immunophenotypic findings of inflammatory pseudotumors of the spleen in eight patients. The primary importance of recognizing these uncommonly found lesions is to distinguish them from malignant lymphoma, which splenic inflammatory pseudotumors may mimic clinically and radiologically. Grossly, the splenic inflammatory pseudotumors in this study ranged from 0.5 to 11.5 cm. One case was multinodular, and seven lesions were solitary. In general, the size of the lesion correlated with the presence of symptoms. The smaller lesions were usually incidental findings, discovered as part of the workup of idiopathic thrombocytopenic purpura (three cases), during staging for Hodgkin's disease (one case), or at autopsy (one case). Microscopically, the lesions were composed of a variable mixture of inflammatory cells admixed within a spindle cell proliferation. Small, cytologically normal lymphocytes and plasma cells were constant features, in a variable mixture, with neutrophilic and eosinophilic leukocytes present in some cases. Coagulative necrosis was located centrally in six lesions; neutrophilic leukocytes were correlated with the presence of necrosis. The presence of necrosis did not correlate with the presence of symptoms. Immunohistochemical studies revealed that the small lymphocytes present were predominantly T cells. Histiocytes and polytypic plasma cells were also numerous, whereas B cells were infrequent. Inflammatory pseudotumors of the spleen are benign lesions. The clinical follow up for the seven patients in this study who underwent splenectomy showed no evidence of recurrence or subsequent development of a hematopoietic neoplasm, with a median follow-up of 18 months (range, 3 to 135 months). PMID- 8368907 TI - Chordoma in childhood and adolescence. A clinicopathologic analysis of 12 cases. AB - Chordoma is a distinctly uncommon neoplasm in the first two decades of life. To characterize further its clinicopathologic features in this age group, we studied 12 chordomas from six males and six females (age range, 1 month to 20 years at diagnosis), with a mean age of 6 years. Six tumors arose in the clivus, four in the cervical or thoracic vertebrae, and two in the lumbar and sacrococcygeal areas. The clinical presentations reflected the location. Histologically, six cases were classic chordomas; the remaining six had atypical or nonclassic features of a round cell or spindle cell tumor. Immunohistochemical stains for vimentin and cytokeratin were positive in all cases tested, whereas epithelial membrane antigen was detected in 11 examples, and S100 protein reactivity was noted in nine lesions. The tumors were uniformly nonreactive for glial fibrillary acidic protein and carcinoembryonic antigen. Electron microscopy in six cases demonstrated large primitive cells with attenuated cell junctions, whorls of cytoplasmic filaments, vacuoles, and glycogen aggregates. Ten children had died of tumor at intervals of 3 weeks to 4.5 years after diagnosis and treatment. Lung, lymph nodes, and other organs were the distant metastatic sites in seven cases. These findings imply that chordomas in children are more variable histologically and may pursue a more aggressive clinical course than their adult counterpart. Immunohistochemical studies are particularly helpful in the differentiation of atypical chordomas from other round and spindle cell neoplasms. PMID- 8368908 TI - Congenital hemangiopericytoma. An ultrastructural, immunocytochemical, and flow cytometric study. AB - Congenital (infantile) hemangiopericytoma is a rare soft-tissue tumor that has been described as a distinct subtype of the classic hemangiopericytoma. We report the ultrastructural, immunocytochemical, and flow cytometric features of a case diagnosed in a male neonate 3 days after birth. The tumor appeared structurally similar to its adult counterpart, meriting the designation hemangiopericytoma, but the improved prognosis that has been reported in young children supports according the infantile form the status of an entity rather than merging it with its adult counterpart. PMID- 8368909 TI - Myasthenia gravis and primary squamous cell carcinoma of the thymus. AB - Occurrence of primary squamous cell carcinoma of the thymus gland in a 65-year old man with myasthenia gravis is reported. Histologic and immunohistochemical studies confirmed the diagnosis of a differentiated squamous cell carcinoma. Extensive clinical investigations ruled out another primary site for the tumor. The patient made a full recovery postoperatively. Only three cases of primary squamous cell carcinoma of the thymus gland in association with myasthenia gravis have been reported in the literature. PMID- 8368910 TI - Solitary cavernous hemangioma of small intestine. Case report and literature review. AB - We describe a 14-year-old boy with a solitary cavernous hemangioma in the proximal small intestine that caused recalcitrant iron deficiency anemia beginning at 3 years of age. After a number of attempts to ascertain the cause of the anemia were unsuccessful, the vascular tumor was ultimately diagnosed in the jejunum, approximately 80 cm distal to the ligament of Treitz. We discuss the differential diagnoses of vasoformative intestinal lesions and review the literature on enteric cavernous hemangiomas in childhood. PMID- 8368911 TI - Intrahepatic and extrahepatic biliary papillomatosis. AB - We report a case of biliary papillomatosis that occurred 8 years after resection of a bile duct tumor. In 1982, a 63-year-old man underwent a cholecystectomy because of cholelithiasis. At operation, a solitary tumor was found in the left intrahepatic bile duct, and a lateral hepatic segmentectomy was performed. The tumor was diagnosed as a benign papillary adenoma. In 1990, mild liver dysfunction was revealed in a routine medical examination. Ultrasonography and computed tomography showed a solid tumor measuring approximately 6 cm in diameter in the left hepatic duct. There was no appearance of jaundice during the course. In 1991, a partial hepatic resection and a bile duct resection were performed. At operation, two tumors were found and removed. These tumors were essentially the same as the bile duct tumor resected 8 years ago. They were diagnosed as biliary papillomatosis. PMID- 8368912 TI - Recruitment of a pathology course director. AB - The process of choosing a course director rarely involves a rigorous examination of the duties to be assumed, primarily because the selection is from among existing faculty rather than as a result of formal recruitment. The selectee tends to be surprised (and often disheartened) by the amount of time the job requires. This report was developed from workshops conducted at recent meetings of both the Group for Research in Pathology Education and the Association of Pathology Chairmen. It describes the overall scope of a course director's activities, including the percentage of time devoted to various functions, and identifies issues to be addressed at the time of the course director's selection. Although the appointment may still be from within the department, the recruitment process does allow for a more full and open discussion of the job to be accomplished. PMID- 8368913 TI - Homosexuality and bisexuality in different populations. AB - The general public as well as the scientific community have use for accurate data on the size(s) of the heterosexual, homosexual, and bisexual populations. Uses include political, legal, medical, and social. The data upon which the typically used figures are dependent have come under scrutiny. This review of studies from the U.S. and elsewhere indicate that it is unreasonable to consider the often used figure of 10% of the male population as more or less regularly engaging in same-sex activities. The figure is closer to half that. And the figure for the lesbian population is even smaller. Further, routinely exclusive or predominantly exclusive homosexual activities are more common than bisexual activities. PMID- 8368914 TI - Expert psychological testimony in cases of alleged child sexual abuse. AB - Concurrent with the rapid rise in allegations of child sexual abuse, psychologists are increasingly assuming the role of experts for the courts. In this position, a new and more controversial role is often assumed by the expert, that of psychological investigator. A review of the common legal contexts for such a role as well as the theoretical and empirical basis for the investigatory role is presented. Ethical issues are also considered. A literature review reveals that many assessment instruments do not meet jurisprudential standards. Suggestions for improving the role of psychological experts in the courtroom include educating the legal audience regarding the limits of psychological testimony, providing standards for qualifications of experts, and emphasizing the data-based probabilistic nature of psychological expert testimony. PMID- 8368915 TI - Sexual preference assessment of sexual aggressors: predictors of penile response magnitude. AB - A current method used to assess the sexual preference of sexual aggressors is the recording of their penile responses during the presentation of erotic stimuli. This method is ineffective in subjects who do not obtain sufficient penile responses. Whether variables related either to the subjects or their crimes would correlate with the magnitude of penile responses during sexual preference assessment was studied. The penile responses of 92 subjects were recorded. Older and pre-sentencing subjects showed a lower maximum penile response magnitude than younger and sentenced subjects. Results are discussed as they relate to the validity of physiological assessment of sexual preference. PMID- 8368916 TI - Reports of female initiation of sexual contact: male and female differences. AB - Women's reports of initiating sexual contact and men's reports of experiencing female initiation were compared. 128 male and 212 female college students were recruited from sexuality classes at three institutions. It was hypothesized that there would be no significant difference between women's reports of initiating sexual contact and men's reports of experiencing female initiation. A chi-square test of significance at the p < 0.05 level with an alpha rate adjustment (p < 0.002) using the Bonferroni technique was implemented. Of 26 questionnaire items, 15 registered significant differences between male and female reports (p < 0.002). Overall, males reported experiencing female initiation more frequently than females reported initiating. Traditional gender roles may influence male and female perceptions of female initiation of sexual contact in a way that contributes to significant differences in reporting. PMID- 8368917 TI - The role of body image in sexually avoidant behavior. AB - "Spectatoring" refers to a cognitive self-absorption, wherein individuals fixate on and carefully monitor personal body parts and/or the adequacy of personal sexual functioning. To examine this process within a university population, undergraduate and graduate students (108 male and 140 female) filled out questionnaires that assessed body image, sexual knowledge, global sexual attitudes (i.e., liberal-conservative), general psychological adjustment, and frequency of sexual behaviors. Multiple regression analyses were used to determine if spectatoring, operationalized by measures of body image, would significantly predict sexually avoidant behavior. Results indicated that body image scores significantly predicted frequency of sexual behaviors for both genders, while general sexual knowledge and psychological adjustment did not predict sexual behavior. Overall, sexual attitude scores were the best predictors of sexual approach/avoidance behaviors for both genders. Implications are drawn for future research using the assessment of more global sex attitudes in the study of spectatoring. PMID- 8368918 TI - Violence and sexual violence in pornography: is it really increasing? AB - Literature and research on the question of the increasingly violent nature of pornography is reviewed. In addition, the paper reports the findings of a content analysis of all cartoons and pictures in Hustler Magazine from 1974 through 1987. Results indicate that sexually violent cartoons and/or pictorials constitute a relatively small proportion of the total cartoons and pictorials. Moreover, no monotonic increase was found in such depictions over the 14-year period examined. In fact, a relatively small and constant proportion of violent and/or sexually violent depictions over this period is reported. These findings are examined in relation to previous research and societal concern about alleged increases in violent pornography as an explanation for increases in rape rates. PMID- 8368919 TI - Gastroesophageal reflux and laryngeal disease. AB - OBJECTIVE: We wanted to determine if surgical correction of gastroesophageal reflux disease (GERD) would affect inflammatory laryngeal lesions in a select group of patients with known GERD and chronic inflammatory laryngeal lesions. DESIGN: Patients with persistent inflammatory lesions in the larynx were referred for workup of GERD when these lesions were not associated with smoking or drinking or when cessation of smoking failed to ameliorate these lesions during a minimum period of 6 months. Twenty-four-hour pH monitoring was used to confirm GERD in 10 patients, while two patients had GERD confirmed radiologically, and one patient had typical symptoms of esophagitis and incompetent lower esophageal sphincter. Thus, 13 patients with chronic laryngeal inflammation persistent after cessation of smoking had concomitant GERD. These patients were all treated with Nissen fundoplication for GERD. SETTING: Patients with chronic laryngitis were referred to an otolaryngologist at a tertiary medical center. PATIENTS: Patients were consecutively selected as they presented with chronic persistent laryngeal lesions and were found to have GERD. INTERVENTIONS: Surgical correction of GERD with Nissen fundoplication. MAIN OUTCOME MEASURES: Status of the larynx was assessed at 3-month intervals with fiberoptic laryngoscopy and symptoms (ie, hoarseness, sore throat) were evaluated. RESULTS: Laryngeal inflammatory lesions and voice changes (hoarseness and sore throat) promptly resolved in eight (73%) of 11 patients. To date, these improvements have continued after a mean follow-up of 11 months. CONCLUSIONS: Correction of GERD in a selected subset of patients with laryngeal inflammatory lesions ameliorates these lesions. PMID- 8368920 TI - A retrospective comparison of transanal surgery and endocavitary radiation for the treatment of 'early' rectal adenocarcinoma. AB - OBJECTIVE: To compare two techniques for the local treatment of "early" rectal adenocarcinoma. DESIGN AND STUDY PARTICIPANTS: A retrospective comparison of 27 patients who underwent transanal disk excision and fulguration (group A) and 38 patients who underwent transanal endocavitary radiation (group B). SETTING: Inpatient and outpatient. INTERVENTION: Group A patients had rectal adenocarcinoma treated with disk excision and fulguration. Group B patients received 100 to 125 Gy in four to five fractions using the Phillips RT-50 unit. MAIN OUTCOME MEASURES: Survival and local recurrence. RESULTS: The median follow up for group A was 68 months; for group B, 38 months. The mean tumor diameter was 2.5 cm, all were grade 1 or 2. The local recurrence rate was 7.4% for group A and 21% for group B. Local recurrence was not correlated with tumor grade, location, or size but did correlate with tumor ulceration. CONCLUSION: For selected early rectal cancers, surgical excision and fulguration offers better local control than endocavitary radiation therapy, while survival was similar. PMID- 8368921 TI - The role of duplex ultrasound arterial imaging in patients with penetrating extremity trauma. AB - OBJECTIVE: To investigate the role of color-flow duplex ultrasound vascular imaging in screening patients for potential arterial injuries following penetrating trauma of the extremities. DESIGN: In this prospective study, patients with penetrating trauma in proximity to major peripheral vessels but without signs of arterial injury underwent color-flow duplex imaging. Patients with abnormal color-flow duplex examination results were then studied with angiography, and the results of the two studies were compared. In patients who presented with signs of arterial injury, immediate operative exploration and/or angiography was performed. SETTING: An urban trauma center. PATIENTS: Patients entering the trauma center with penetrating trauma between April 1991 and December 1992. RESULTS: Seventy-seven patients with 86 extremity injuries were initially screened with color-flow duplex imaging. Four patients had positive study results, and all injuries were confirmed with angiography (100% true positive). No missed arterial injuries were detected in clinical follow-up. CONCLUSIONS: Color-flow duplex imaging reliably detects occult arterial injuries and may also have a role in following up minor injuries treated without surgery. PMID- 8368922 TI - Accuracy of ultrasound in the diagnosis of acute appendicitis compared with the surgeon's clinical impression. AB - OBJECTIVE: To compare the accuracy of the surgeon's clinical diagnosis of acute appendicitis with that of an ultrasonographic examination of the abdomen. DESIGN: Prospective trial. SETTING: US Navel Hospital, San Diego, Calif. PATIENTS: One hundred ten patients admitted to the hospital with suspected appendicitis from May 1990 to June 1992. INTERVENTION: Symptoms and signs for each patient were recorded, along with the surgeon's clinical impression of immediate surgery or observation. The patient then underwent an ultrasound examination performed by a staff radiologist. On the basis of the ultrasound findings the patient was placed into one of three categories: appendicitis, normal examination results, or other conditions. Patients with an ultrasound-based diagnosis of appendicitis proceeded to the operation, regardless of the surgeon's clinical impression. Those with other conditions diagnosed with ultrasonography were treated as was appropriate for the condition. RESULTS: The ultrasound-derived diagnosis of appendicitis had a sensitivity of 85.5%, a specificity of 84.4%, a positive predictive value of 88.3%, a negative predictive value of 80.1%, and an overall accuracy of 85.0%. The surgeon's clinical impression at the time of admission had a sensitivity of 62.9%, a specificity of 82.2%, a positive predictive value of 82.9%, a negative predictive value of 61.7%, and an overall accuracy of 71.2%. CONCLUSION: The overall accuracy of ultrasonography in the diagnosis of appendicitis was statistically superior to that of the surgeon's clinical impression (P < .0001). However, 24% of the patients with normal ultrasound findings were ultimately found to have appendicitis at operation, emphasizing the point that ultrasonography cannot be relied on to the exclusion of the surgeon's careful and repeated evaluation. PMID- 8368923 TI - The Whipple procedure for severe complications of chronic pancreatitis. AB - OBJECTIVE: To analyze the clinical indications and long-term results for the Whipple procedure used for severe complications of chronic pancreatitis (CP). DESIGN: A series of 28 patients requiring the Whipple procedure for CP were reviewed by one surgeon between 1986 and 1993. SETTING: A multispecialty group practice hepatobiliary pancreatic referral center. PATIENTS: The referred patients with CP complications in the pancreatic head were anatomically defined by endoscopic retrograde cholangiopancreatographic and computed tomographic scans to include expanding pseudocysts, pancreatic duct disruption, arteriovenous fistula, or calcified obstructive fibrosis of bile duct, pancreatic duct, and/or duodenum. INTERVENTION: The Whipple procedure (pylorus-preserving [n = 25] or standard [n = 3]) was performed after preoperative assessment with a mesenteric arteriogram and, as necessary, percutaneous drainage or endoscopic stenting of pseudocyst, pancreatic duct, or bile duct were performed. MAIN OUTCOME MEASURES: Mortality, morbidity, length of hospital stay, and long-term results of the operation. RESULTS: There was no mortality. A 36% morbidity rate included adult respiratory distress syndrome (n = 3) secondary to a long operation time (average, 9.8 hours) or infected tissue and delayed gastric function (> 14 days) secondary to retrogastric amylase-rich fluid collections (n = 4). Long-term follow-up in 25 patients after 27 months (range, 3 to 84 months) showed that 88% were pain-free and 12% had improved. None had recurrent pancreas problems, but 28% had resumed drinking alcohol. Inability to gain weight was noted in 4% and a marginal ulcer in 4%. CONCLUSIONS: The Whipple procedure for severe complications of CP in the pancreatic head is a safe and effective operation leaving little gastrointestinal sequelae. Preoperative endoscopic and radiological assessment, drainage, and stenting procedures are key elements to achieving positive results. PMID- 8368924 TI - Gallbladder cancer discovered during laparoscopic surgery. Potential for iatrogenic tumor dissemination. AB - OBJECTIVE: To examine the results of treatment of laparoscopically discovered gallbladder cancer. DESIGN: Retrospective review of clinical data for the 10 patients with laparoscopically discovered gallbladder cancer who were referred to our institution for definitive surgical therapy. SETTING: An oncologic referral center. PATIENTS: All patients in the 24-month period from November 1990 to November 1992 with this entity who were referred for surgical therapy. INTERVENTION: Exploratory laparotomy was performed on all patients. Resection with curative intent was performed when possible. MAIN OUTCOME MEASURES: Resectability and outcome of cancer treatment. RESULTS: In three patients, a subsequent radical resection was performed and as a result, two patients are currently free of disease. Intraperitoneal spread, not present at the original laparoscopy and associated with violation of tumor at laparoscopy, precluded potentially curative resection for four patients. In two of these patients, there was obvious tumor growth within the laparoscopy tracts. CONCLUSIONS: Tumor dissemination is a real hazard of laparoscopic violation of gallbladder integrity in the presence of gallbladder cancer. Modification of management based on awareness of such a hazard is needed to improve resectability and outcome of future cases of laparoscopically discovered gallbladder cancer. PMID- 8368925 TI - Hepatic flow scintigraphy in evaluation of hepatic metastases in patients with gastrointestinal malignancy. AB - OBJECTIVE: To assess the value of hepatic flow scintigraphy for occult metastases. DESIGN: Prospective study, 2 years of follow-up. SETTING AND STUDY PARTICIPANTS: One hundred twenty-nine patients undergoing surgery for gastrointestinal cancer. INTERVENTION: Preoperative hepatic flow scintigraphy (3mCi of technetium-99m). MAIN OUTCOME MEASURE: Development of hepatic metastases. RESULTS: Hepatic flow scintigraphy had a sensitivity of 92% and a specificity of 34%. The positive and negative predictive values were 15% and 97%, respectively. CONCLUSIONS: Hepatic flow scintigraphy could therefore be useful in identifying patients who are at low risk of developing metachronous liver metastases and thus avoid unnecessary adjuvant chemotherapy following resection of the primary tumor. PMID- 8368926 TI - Total lobectomy and total thyroidectomy in the management of thyroid lesions. AB - OBJECTIVE: To study an unselected consecutive series of patients undergoing thyroidectomy for tumors to establish the complication rates of total lobectomy with isthmectomy and total thyroidectomy. DESIGN: Retrospective study. PATIENTS: Two hundred eight consecutive, unselected patients were operated on by one surgeon from 1980 to 1990. One hundred nineteen patients (57%) had a total lobectomy and isthmectomy and 85 patients (41%) had total thyroidectomy. Four patients (2%) had partial excision for technical reasons, two with anaplastic cancers and two with advanced thyroiditis. RESULTS: Forty-two malignant lesions (20%) were diagnosed with a mean follow-up of 5 years. Malignant lesions were diagnosed in 15 (31%) of 48 males and 27 (17%) of 160 women. Ten patients (5%) had parathyroid adenomas. Long-term follow-up revealed that there were no deaths, permanent hypocalcemia, or recurrent laryngeal nerve damage. One patient was returned to the operating room to control bleeding. CONCLUSION: This study suggests that total thyroid lobectomy with isthmectomy and total thyroidectomy are both safe procedures in the management of thyroid tumors. PMID- 8368927 TI - Hepatic resection for hepatolithiasis. AB - OBJECTIVE: To analyze the results of hepatic resection for hepatolithiasis. DESIGN: A retrospective study of case records of patients with hepatolithiasis undergoing hepatic resection. These patients had been followed up for 3 to 38 months. They were referred to Queen Mary Hospital, a tertiary referral center in Hong Kong. PATIENTS: Of 172 patients with hepatolithiasis seen between January 1984 and December 1981, 63 patients underwent hepatic resection because the affected liver segments were destroyed by repeated infection (n = 51), multiple cholangitic liver abscesses were found in the affected liver segments (n = 9), or concomitant intrahepatic cholangiocarcinoma was diagnosed (n = 3). INTERVENTION: Left lateral segmentectomy was performed in 42 patients, left hepatic lobectomy in 15 patients, right hepatic lobectomy in one patient, and segmentectomy in five patients. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality analysis. RESULTS: Contrary to hepatic resection in a normal liver, dissection to isolate inflow and outflow vasculature was difficult in 52% of cases owing to severe inflammatory fibrosis at the liver hilum, at the umbilical fissure, or at the junction of hepatic vein with inferior vena cava. The operative morbidity rate was 32% and the mortality rate was 2%. The majority of complications were wound infection, subphrenic abscesses, or biliary fistulas, which could be due to the presence of infected bile (85%) and liver abscesses (25%) in this disease. Statistical analysis of the preoperative hematological and biochemical variables and the amount of intraoperative blood loss could not identify any factor with significance in correlating with the development of postoperative complications. Stones recurred in 16% after a median follow-up of 47 months. CONCLUSION: Hepatic resection is a satisfactory treatment for hepatolithiasis. The postoperative septic complication rate is high and is an intrinsic problem related to liver resection in a septic condition. PMID- 8368928 TI - Emergent liver transplantation to salvage a hepatic avulsion injury with a disrupted suprahepatic vena cava. PMID- 8368929 TI - Pneumonia due to stress ulcer prophylaxis with cimetidine: a necessary consequence? PMID- 8368930 TI - Frozen-section diagnosis of breast biopsy specimens. A necessary procedure? PMID- 8368931 TI - Pacific Coast Surgical Association. Surgeons and the evolution of vascular surgery. PMID- 8368932 TI - Preperitoneal prosthetic herniorrhaphy. One surgeon's successful technique. AB - OBJECTIVES: To review the senior author's experience with preperitoneal mesh inguinal herniorrhaphy, evaluate the recurrence rate, and compare it with previously published data and with the developing technique of laparoscopic herniorrhaphy. DESIGN: A retrospective records review of 204 herniorrhaphies, follow-up of patients (mean follow-up, 3.5 years), and review of the literature. SETTING: One general surgeon's clinical practice in an 860-bed regional referral hospital. PATIENTS: One hundred sixty-two men and 13 women (mean age, 63 years) who underwent preperitoneal prosthetic herniorrhaphy by the senior author between 1984 and 1991 and whose medical records were available for review (175 [96%] of 183 patients). MAIN OUTCOME MEASURES: Short- and long-term postoperative complications and hernia recurrence. RESULTS: One hundred fifty-two primary and 52 recurrent inguinal hernias were repaired using a preperitoneal prosthetic approach and either general or regional anesthesia. Wound complications occurred in 12 (5.9%) of 204 operations, and one recurrence (0.5%) was detected over the mean long-term follow-up period of 42 months (range, 7.9 to 110 months). A 25 year recurrence rate of 1% was predicted. CONCLUSIONS: This repair compares favorably with similar, previously reported repairs and is suggested as a standard for comparison with the developing technique of laparoscopic herniorrhaphy. PMID- 8368933 TI - Radial or ulnar artery laceration. Repair or ligate? AB - OBJECTIVE: To determine the relationship between patency of radial or ulnar artery repair and later hand symptoms. DESIGN: Call-back survey. SETTING: Urban trauma center. PATIENTS: Thirty-two subjects with wrist artery lacerations undergoing 26 arterial repairs and six artery ligations during an 8-year period. INTERVENTIONS: Directed history and hand examination (palpation of wrist pulses, Doppler Allen test, and Doppler interrogation of palmar arch and digital vessels). MAIN OUTCOME MEASURES: History of hand claudication, weakness, or cold sensitivity or paresthesias and patency of wrist arteries. RESULTS: Twelve (46%) of 26 wrist artery repairs were patent. There was no evident benefit of optical magnification or specialization in hand or vascular surgery. No subjects had hand claudication; there was a 50% incidence of hand weakness and a 12% incidence of cold sensitivity independent of patency of the damaged wrist artery and present only in subjects with associated nerve injury. Professional charges for wrist artery repair were threefold to fourfold higher than those for wrist artery ligation. CONCLUSION: Consonant with prior reports, patency following repair of radial or ulnar artery laceration does not exceed 50%. Later hand symptoms relate to nerve or tendon damage, not to arterial patency. In the absence of acute hand ischemia, simple ligation of a lacerated radial or ulnar artery is safe and cost effective. PMID- 8368934 TI - Popliteal-tibial bypass grafts in the management of limb-threatening ischemia. AB - OBJECTIVES: To ascertain the cumulative rates of primary graft patency and limb salvage and the frequency of proximal arterial disease progression in patients with autologous saphenous vein bypass grafts that originate from the popliteal artery and whose operative indication was limb-threatening ischemia. DESIGN: Five year retrospective study with follow-up that ranged from less than 1 month to 60 months. SETTING: Tertiary care center. PATIENTS: Twenty-four threatened limbs in 23 patients were reviewed. Surgical indications included gangrene in 15 limbs (63%), rest pain in seven limbs (29%), and a nonhealing ulcer in two limbs (8%). Patients with previous ipsilateral infrainguinal arterial reconstructive procedures were excluded. Mean patient age was 66 years, and 18 patients 78% had insulin-dependent diabetes mellitus. MAIN OUTCOME MEASURES: Percentages of primary graft patency and limb salvage were determined by the life-table method. Proximal arterial disease progression was assessed via follow-up arteriography or segmental limb pressures. RESULTS: The cumulative rates of primary graft patency and limb salvage at 1, 3, and 5 years were 73%, 59% and 59%, and 87%, 57%, and 57%, respectively. No patient developed proximal arterial disease progression that required intervention during the study period. CONCLUSIONS: The cumulative rates of primary graft patency and limb salvage were essentially the same, which indicated poorly collateralized limbs that are solely dependent on the graft. There did not appear to be a critical progression of proximal arterial disease that would warrant a more proximal graft origin. A short autologous saphenous vein graft that originates from the above-knee or below-knee popliteal artery is a durable bypass. PMID- 8368935 TI - The value of sham-feeding tests in patients with postgastrectomy syndromes. AB - OBJECTIVE: The value of gastric secretory testing in surgical practice has been questioned. Sham feeding (SF) is a test of gastric secretion that determines the status of gastric vagal innervation or incomplete vagotomy. Our purpose was to show that the results of SF tests affect operative strategy and/or clinical management. DESIGN: The medical records of 30 consecutive patients studied with SF in our laboratory were reviewed to determine if patient management was affected by the results of SF. PATIENTS: All 30 patients had prior vagotomies. Sham feeding was performed in patients (1) before planned reoperation for postgastrectomy syndromes (n = 17), (2) with peptic ulcerations/pain of unclear etiology (n = 8), or (3) postoperatively in those who were at high risk for recurrent ulcer (n = 5). RESULTS: Sham feeding indicated complete vagotomy in 16 patients and incomplete vagotomy in 14 patients. In 17 patients studied before planned reoperation, operative strategy was affected by results of SF in 15 cases; five patients had revagotomies performed at reoperation, 11 did not, and one patient had her operation canceled. In patients with atypical postoperative ulcers/pain, management was changed in only two of eight patients. In the high risk patients studied postoperatively, management was affected in four of five patients. CONCLUSIONS: (1) We believe that our results justify the performance of SF before any reoperation on the stomach, since an operative plan was nearly always affected. (2) In patients with atypical peptic complaints after gastric surgery, SF usually (80%) confirmed acid hypersecretion, thereby affecting management less often. (3) Although unproved, we believe SF results can guide the use of "prophylactic" H2-blockers in treating selected high-risk postgastrectomy patients. PMID- 8368936 TI - Transplantation and reanimation of hearts removed from donors 30 minutes after warm, asystolic 'death'. AB - OBJECTIVE: To test whether hearts from "dead," pulseless, asystolic donors could be transplanted and reanimated successfully using reperfusion manipulations. DESIGN AND INTERVENTIONS: Ten infant lambs (mean [+/- SD] weight, 4 +/- 1 kg) were anesthetized and pretreated with 50% dextrose, methylprednisolone, prostaglandin E1, and sublingual nifedipine. Five of these lambs were paralyzed; hypoxic asystolic arrest occurred 10 +/- 2 minutes later. Thirty minutes following asystole (mean, 40 +/- 2 minutes after paralysis) sternotomy was performed and the hearts were excised. Aortic blood gases were as follows: pH, 6.6 +/- 0.1; PCO2, 180 +/- 20 mm Hg; and PO2, 8 +/- 2 mm Hg. Donor hearts were given 30 mL/kg of Cardiosol (Water's Instrument Co, Danburg, Conn), a new cardioplegic agent, at 4 degrees C, and explanted into iced saline. The remaining five lambs then underwent cardiopulmonary bypass, were cooled to 20 degrees C, and hypothermic arrest was instituted. After excision of the recipient's heart, the donor heart was implanted in an orthotopic position. Total cold ischemic time was 1 hour 40 minutes +/- 10 minutes. The donor heart was retroperfused for 10 minutes with low-hematocrit, low-calcium blood via a coronary sinus catheter, then normal aortic inflow reperfusion was continued for 50 minutes. MAIN OUTCOME MEASURES: Removal of the cardiopulmonary bypass and measurement of hemodynamic parameters. RESULTS: One half hour after the bypass, mean systolic aortic pressure was 71 +/- 6 mm Hg; mean right atrial pressure was 6 +/- 2 mm Hg; mean left atrial pressure was 7 +/- 2 mm Hg; and mean pulmonary arterial pressure was 20 +/- 8 mm Hg. No inotropic drugs were given for postbypass blood pressure support. CONCLUSION: It is possible to transplant and reanimate hearts that have been dead for 30 minutes. When further developed, the use of donors who were not brain dead but allowed to die naturally could greatly increase the donor pool. PMID- 8368937 TI - Diagnosis and treatment of bowel perforation following pediatric orthotopic liver transplantation. AB - OBJECTIVE: Bowel perforation is a frequent cause of mortality after pediatric orthotopic liver transplantation. The aims of this study were to identify the cause of this phenomenon and to examine current methods of treatment. DESIGN: This is a retrospective analysis of 246 pediatric patients who underwent orthotopic liver transplantation at a large, urban, tertiary care medical center between 1984 and 1992. We examined the frequency of bowel perforations after transplantation and identified predisposing factors and signs. In this series, bowel perforations occurred in 24 of 246 recipients and were common in those who had previous liver-related surgery (22 patients). Clinical signs included fever (13 patients), leukocytosis (14 patients), and free air on abdominal roentgenograms (11 patients). RESULTS: Perforation occurred at the Roux-en-Y limb in 15 of 24 recipients as well as in the right transverse colon (five patients), terminal ileum (three patients), and duodenum (one patient). The repair was resection and/or primary closure (18 patients), or diversion (six patients). Recurrent perforations (nine patients) could not be attributed to the method of the repair. Perforation-related sepsis was the primary cause of death in 12 patients (50%) and was more common among patients who developed recurrent perforation (seven [78%] of nine patients). CONCLUSIONS: The occurrence and location of bowel perforation after pediatric orthotopic liver transplantation suggests that the cause is related to bowel injury during difficult hepatectomy. Mortality may be reduced by early second-look operations in high-risk patients. PMID- 8368938 TI - Changes in peripheral nervous system activity produced in rats by prenatal exposure to carbon monoxide. AB - The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady state Na inactivation, h infinity (V), showed that the percentage of the maximum number of activable Na channels at the normal resting potential (-80 mV) was increased to approximately 85% in CO-exposed rats. Moreover, the voltage-current relationship showed a negative shift of sodium equilibrium potential in CO treated animals. In 270-day-old CO-exposed rats, parameters of sodium inactivation were not significantly modified; the reversal potential was still lower with respect to controls. The results indicate that prenatal exposure to mild CO concentrations produces reversible changes in sodium inactivation kinetics and on irreversible change in sodium equilibrium potential. These alterations could reflect CO influence on the rate of ion channel development. PMID- 8368939 TI - Biphasic action of sarin on monosynaptic reflex in the neonatal rat spinal cord in vitro. AB - The action of sarin, an organophosphorus (OP) compound, was examined in vitro for its effects on the spinal monosynaptic reflex (MSR) in neonatal rats. The effects of sarin were biphasic, i.e. facilitation at lower concentrations (2-20 nM) followed by depression of the MSR at concentrations above 30 nM. Facilitation of MSR was maximal (150% of control) at 20 nM sarin. The depression of MSR was maximal (70% of control) at 200 nM sarin, with half maximal inhibition occurring at 90 nM sarin. Atropine (200-500 nM) effectively reversed the depression caused by sarin, while pretreatment with low concentrations of atropine (10 nM) completely blocked the depression otherwise observed with sarin. Benactyzine was also effective in preventing sarin-induced depression, while pirenzepine was less effective. The nicotinic blocking agents tubocurarine and mecamylamine were, however, ineffective in preventing or reversing sarin-induced depression. The facilitation of MSR seen with lower concentrations (2-20 nM) correlated well with the blockade of late phase inhibition (between 30 and 50 ms conditioning-test interval) elicited in spinal cord by stimulating the adjacent dorsal root at various condition-test intervals, which has been shown elsewhere to be sensitive to bicuculline (Deshpande and Warnick 1988). Thus it is speculated that sarin at lower concentrations blocks GABA transmission, producing facilitation, and at higher concentrations activates the muscarinic receptors producing depression of MSR. The beneficial action of pretreatment with antimuscarinic agents may be attributed to the protection of the muscarinic receptors. PMID- 8368940 TI - Renal toxicity of aristolochic acid in rats as an example of nephrotoxicity testing in routine toxicology. AB - The nephrotoxic action of aristolochic acid (AA) was investigated in female Wistar rats given single doses of 10, 50 or 100 mg/kg by gastric tube. Renal lesions developed within 3 days, the effect being dose-dependent. Histologically, there was evidence of necrosis of the epithelium of the renal tubules, and functionally, there were rises in plasma creatinine and urea together with increases in urinary glucose, protein, N-acetyl-beta-glucosaminidase, gammaglutamyl transferase and malate dehydrogenase. Taking AA as an example, the aim of the present study was to consider the suitability of this model, based on a combination of histology and laboratory investigations, as a short-term test for the detection of nephrotoxic agents. PMID- 8368941 TI - Pulmonary clearance and toxicity of intratracheally instilled cupric oxide in rats. AB - Pulmonary clearance and toxicity of cupric oxide (CuO) dusts, which are probably formed in refining and smelting factories, were investigated. Groups of three rats received intratracheal (i.t.) instillation of CuO at a dose of 20 micrograms Cu/rat in time-course experiments (up to 7 days post-instillation). Other groups of three rats received i.t. instillation of CuO at doses of 2.5, 5, 10, 30, 50 and 100 micrograms Cu/rat and were killed at 2 days post-instillation in dose effect experiments. Intratracheally instilled CuO particles were cleared from the lung with a half-time of 37 h. Copper binding metallothionein (MT) was induced in a dose-dependent manner and detected at 12 h to 3 days post-instillation. Rapid clearance of CuO from the lung and induction of MT at 12 h post-instillation suggest that CuO particles were solubilized and then cleared from the lung. The acute pulmonary toxicity of CuO was evaluated by cytological (numbers of macrophages and polymorphonuclear leukocytes), biochemical and elemental inflammatory indices (lactate dehydrogenase and beta-glucuronidase activities and protein, sulfur, phosphorus and calcium contents) in the bronchoalveolar lavage (BAL) fluid. These inflammatory indices peaked at 12 h to 3 days post instillation, and increased with dose over the dose range, except for phosphorus content. Dose-effect relationships in BAL inflammatory indicators of CuO-injected (i.t.) groups were compared to those of CuSO4-injected (i.t.) groups. The results of the comparison indicated that there was no significant difference in acute inflammatory potency between CuSO4 (soluble form of Cu) and CuO (insoluble form of Cu) in the rat lung. PMID- 8368942 TI - Toxicological studies with primary cultures of chick embryo cells: DNA fragmentation under the influence of DNase I-inhibitors. AB - Chicken embryo brain and liver cells in vitro exhibited spontaneous DNA fragmentation as determined by viscometry of alkaline cell lysates. Ca2+ and Mg2+ enhanced, while Zn2+, the Ca2+ chelator ethylenglycol-bis(beta-aminoethyl-ether) N,N,N'-tetraacetic acid (EGTA), spermine and--to a lesser extent--spermidine and Hoechst 33,258 inhibited spontaneous DNA fragmentation. Under the same conditions chromatin condensation, as assessed by nucleoid sedimentation, increased. Exposure of chicken embryo cells to various genotoxic agents, i.e. doxorubicin, bleomycin, methyl methanesulfonate, thiyl radicals, H2O2, UV light, and X-rays, increased DNA fragmentation in a dose dependent manner. Zn2+ or EGTA diminished DNA fragmentation in cells exposed to bleomycin, thiyl radicals, H2O2 and UV light. An apparent sensitisation to X-irradiation has been observed in Zn2+ or EGTA-pretreated cells. It is suggested by the present investigations that, with agent specific peculiarities, apoptotic phenomena are implicated when nucleotoxicity is assessed in chicken embryo cells by physico-chemical short-term tests in vitro. PMID- 8368943 TI - Changes in the contractile responses to carbachol and in the inhibitory effects of verapamil and nitrendipine on isolated smooth muscle preparations from rats subchronically exposed to Co2+ and Ni2+. AB - Male Wistar rats were exposed to subtoxic doses of Co2+ or Ni2+, receiving Co(NO3)2 or NiSO4 with drinking water for 30 days. No significant differences in the body weight and no visible changes in the behaviour of the controls and experimental animals were established. Cumulative concentration-effect curves for carbachol were obtained in ileum and trachea isolated from control and Co(2+)- or Ni(2+)-treated rats. The effect of the Ca2+ antagonists on the carbachol-induced contractions was studied by adding increasing concentrations of verapamil or nitrendipine to the bath solution 20 min prior to carbachol. The results showed that exposure of rats to subtoxic doses of Co(NO3)2 or NiSO4 altered the contractile responses to carbachol. The changes in the pD2 values and the shift to the left of the concentration-effect curves suggest a higher sensitivity to carbachol in preparations from the ileum of Co(2+)- or Ni(2+)-exposed rats. The tracheal strips isolated from control and heavy metal-treated rats showed a less potent sensitiveness to carbachol as compared to the ileal segments. An opposite tendency for decreased cholinergic reactivity was observed in tracheal strips from Co(2+)- and Ni(2+)-treated animals. The inhibitory effect of the Ca(2+) antagonists on the contractility of ileal preparations from Co(2+)-treated rats increased at all concentrations of verapamil and at the highest concentration of nitrendipine, but decreased at lower concentrations of nitrendipine. The effect of verapamil on the preparations from Ni(2+)-exposed rats was unchanged or even decreased at higher verapamil concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368944 TI - Comparative effect of cadmium on osteoblastic cells and osteoclastic cells. AB - Cadmium(Cd) has been thought to disturb the bone metabolism directly. The mechanism for the bone lesion is unknown, however. To examine the effects of cadmium on bone metabolism, we compared its effects on osteoblasts and osteoclasts in vitro. We used an established cell line, MC3T3-E1, as osteoblasts and tartrate resistant acid phosphatase (TRACP)-positive multi-nucleated cells (MNC) formed by a bone marrow culture system as osteoclasts. Alkaline phosphatase (ALP) activity was decreased by 10(-7) M Cd and DNA content and hydroxyproline content of osteoblastic cells were decreased by 10(-5) M Cd. Cadmium at 10(-7) M inhibited the osteoclastic cell formation from mouse bone marrow in the presence of 10(-8) M 1 alpha, 25(OH)2 vitamin D3. A 100-fold higher concentration of zinc(Zn) simultaneously added to the cadmium-containing medium prevented the toxicity of cadmium to osteoclastic cells as observed in the culture of osteoblastic cells. These results indicate that both bone formation and bone resorption are inhibited by cadmium. The responses of osteoclasts and osteoblasts to cadmium in this culture system were the same and the responses of cadmium damaged osteoblasts and osteoclasts to zinc were also similar. These results suggest that another mechanism by which cadmium could cause bone damage should be considered in addition to the specific induction of osteoclastic cells by Cd. PMID- 8368945 TI - Enhancement of myelotoxicity induced by repeated irradiation in mice exposed to a mixture of groundwater contaminants. AB - As part of a program on the toxicology of chemical mixtures at the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP), hematopoietic functions were studied in female B6C3F1 mice treated with 0, 1%, and 5% of a chemical mixture stock of 25 groundwater contaminants in drinking water for 31.5 weeks. The toxicologic interaction between continuous exposure to groundwater contaminants and stress induced by multiple irradiation on hematopoiesis was investigated. For those mice receiving both the chemical mixture and irradiation, the exposure to the former was continuous throughout the 31.5-week experimental period, whereas whole body irradiations (4 times at 200 rads/each) were carried out at 7-week intervals with the first one at 3.5 weeks. Myelotoxicity assessment was made by determining the number of granulocyte macrophage progenitor cells (CFU-GM) 1 week after each irradiation and also at 6 weeks following irradiation as a measure of recovery from stress. Non-irradiated mice treated with 5% chemical mixture solution showed suppression of CFU-GM after 15.5 weeks and became progressively more affected (only 70% of controls by 31.5 weeks of treatment). The population of CFU-GM in mice treated with 5% chemical mixture for 4.5 weeks plus irradiation (1 week after first irradiation) was only 22% of the non-irradiated vehicle control group. This combined (i.e., chemical mixture plus irradiation) suppression of CFU-GM intensified after repeated irradiation until the number of CFU-GM was only 10.7% following the fourth irradiation at 25.5 weeks. Thus, irradiation caused a significant reduction in CFU-GMs in all mice but the effects were more pronounced in mice treated with a chemical mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368946 TI - Degradation of methyl and ethyl mercury by singlet oxygen generated from sea water exposed to sunlight or ultraviolet light. AB - Photodegradation of methyl mercury (MeHg) and ethyl Hg (EtHg) in sea water was studied by sunlight or ultraviolet (UV) light exposure, and by determining inorganic Hg produced by degradation. Sea water containing 1 microM MeHg or EtHg was exposed to sunlight or UV light. N-Acetyl-L-cysteine was added to the solution for preventing Hg loss during the light exposure. MeHg and EtHg in sea water were degraded by sunlight (> 280 nm), UV light A (320-400 nm) and UV light B (280-320 nm), though the amounts of inorganic Hg produced from MeHg were 1/6th to 1/12th those from EtHg. Inorganic Hg production was greater with increasing concentration of sea water. Degradation of MeHg and EtHg by the UV light A exposure was inhibited by singlet oxygen (1O2) trappers such as NaN3, 1,4 diazabicyclo[2,2,2]octane, histidine, methionine and 2,5-dimethylfuran. On the other hand, inhibitors or scavengers of superoxide anion, hydrogen peroxide or hydroxyl radical did not inhibit the photodegradation of alkyl Hg. These results suggested that 1O2 generated from sea water exposed to sunlight, UV light A or UV light B was the reactive oxygen species mainly responsible for the degradation of MeHg and EtHg. PMID- 8368947 TI - Has reactive oxygen a role in methylglyoxal toxicity? A study on cultured rat hepatocytes. AB - The toxicity of methylglyoxal and its ability to generate reactive oxygen species were investigated in cultured rat hepatocytes. Under aerobic and anaerobic conditions methylglyoxal increased lactate dehydrogenase (LDH) release and trypan blue uptake in a concentration dependent manner. Those concentrations of methylglyoxal causing cell injury (1 mM <) also caused the release of reactive oxygen species as indicated by peroxidase-catalyzed luminol chemiluminescence. Release of reactive oxygen was detectable only under aerobic conditions, and only became significant when a large portion of the cells had already lost their viability. It is concluded that methylglyoxal injuries cultured rat hepatocytes and induces the generation of reactive oxygen species. The reactive oxygen species, however, are essentially not involved in methylglyoxal hepatotoxicity but are released by already severely injured cells. PMID- 8368948 TI - The use of nipple shields by breastfeeding women. AB - The use of nipple shields when breastfeeding has given rise to concerns about possible harmful effects. A study was carried out to examine this issue. A lactation consultant's (LC) patients using nipple shields were compared with her other patients who were not using nipple shields, and an incidental sample of all postnatal breastfeeding women. The three groups were compared on discharge from hospital and at 3 months. Breastfeeding rates and problems (nipple trauma and mastitis) were studied: on discharge from hospital the LC patients who were not using nipple shields were significantly less likely to be breastfeeding than either of the other two groups. At 3 months, both LC groups were less likely to be breastfeeding than the postnatal group; there was no significant differences between the women using nipple shields and those who were not. There were no significant difference in reported problems in the 3 groups. It is concluded that women with breastfeeding problems are more likely to give up breastfeeding than those women who do not have major problems, and that the use of nipple shields is not a contributing factor and does not appear to compromise lactation. PMID- 8368949 TI - Refusal to consent: can it be ignored? AB - The common law has long recognised the right of competent adults to autonomy and self determination and this has been held to apply to the right to refuse medical and surgical treatment even when refusal could lead to severe detriment to the individual's life and health. Those who work with patients in a health profession can be faced with a refusal to consent to treatment when the best clinical opinion is that the treatment is appropriate and necessary, and considered to be in the patient's best interests. There have been no clear guidelines which health professionals can follow in deciding to treat or not treat in the presence of a patient's refusal. Where the patient continues to be competent there is an opportunity to take the matter up again with him or her as circumstances change. However, when the patient loses competence, a clinical dilemma arises. There are documented legal cases in which courts have authorized treatment of competent adults even when they have refused or are refusing treatment. Some of these cases involve saving the life of an unborn child. The question which arises is whether different principles apply when an unborn child is involved. To date most of the cases have been heard in North American courts. However, there have been two recent cases in England where courts have authorized treatment without consent when the subjects have apparently had the capacity to make a decision to refuse treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368950 TI - Site comparisons of dentine collagen cross-links from extracted human teeth. AB - Covalent intermolecular cross-links in collagen provide the dentine matrix with stability and tensile strength. The density of collagen cross-links varies depending on the site within the same tissue. This variation is probably due to factors such as the different amounts of stress and different turnover rates at the respective sites. The aim was to quantify the collagen cross-links in different tooth groups as an adaptation to functional requirements. For this purpose, the types and content of major cross-links in dentine collagen of human teeth from three different sites were measured and compared: incisors, premolar canines and molars. After removal of cementum and pulp, 23 extracted teeth at different ages (27-69 yr) were individually pulverized and demineralized with EDTA. Collagen was reduced with standardized NaB3H4, hydrolysed, and subjected to amino acid and cross-link analyses. Each cross-link was quantified on the basis of mole per mole of collagen. The results indicated: (1) all teeth contained labile, reducible (dehydro-dihydroxylysinonorleucine and dehydro hydroxylysinonorleucine) and stable, non-reducible (pyridinoline and its lysyl analogue) cross-links, and (2) the content of both reducible and non-reducible cross-links was least in incisors and greatest in molars. This suggests that dentine collagen matrix maybe functionally adaptive. PMID- 8368951 TI - Survival and neurite formation of mesencephalic trigeminal neurones of the rat in vitro. AB - In order to study the development and functional properties of single, isolated, rat mesencephalic trigeminal neurones, a cell-culture procedure was developed for these specific primary sensory neurones. Mesencephalic trigeminal neurones were isolated from the brainstem of 16-day-old rat embryos. Various factors thought to promote the survival and growth of these neurones in vitro were examined. Outgrowth and maintenance of mesencephalic trigeminal neurones in vitro appeared to be stimulated by a muscle-derived factor, present in muscle-conditioned medium or in muscle extract. Of the neurotrophic factors examined, brain-derived neurotrophic factor and neurotrophin-3, but not nerve-growth factor, promoted the survival of rat mesencephalic trigeminal neurones. Optimal survival of these neurones was found to occur on a monolayer of astrocytes, an effect mediated through direct cell-to-cell interactions. PMID- 8368952 TI - Evidence for up-regulation of epidermal growth-factor receptors on rat periodontal ligament fibroblastic cells associated with stabilization of phenotype in vitro. AB - This study sought to understand the role of epidermal growth factor receptor (EGF R) in periodontal ligament (PDL) fibroblasts. Rat PDL fibroblastic cells and ROS 17/2.8 cells (highly differentiated osteoblastic osteosarcoma cells) were cultured and treated with transforming growth factor-alpha (TGF-alpha), EGF, dexamethasone (Dex) or a combination of EGF and Dex. Alkaline phosphatase (ALP) activity, an early differentiation marker for mineralized tissue-forming cells, was measured using p-nitrophenylphosphate as a substrate. For Scatchard analysis of [125I]-EGF binding, cells were incubated in Dulbecco's modified Eagle's medium containing 0.2% bovine serum albumin and 0-64 ng/ml of [125I]-EGF for 4 h at 4 degrees C. Also, the synthesis of EGF-R protein and the expression of mRNA for EGF-R were measured by immunoprecipitation and Northern blot analysis, respectively. Untreated PDL fibroblastic cells showed a gradual increase in spontaneous ALP activity from 32.4 U/10(6) cells at 2 days to 49.6 U/10(6) cells at 7 days of culture. ALP activity was further increased to 70.8 U/10(6) cells at 7 days after treatment with Dex, whereas EGF treatment reduced it to 19.4 U/10(6) cells. Culture of PDL fibroblastic cells in the presence of a combination of Dex and EGF decreased the Dex-induced ALP activity from 70.8 U to 41.8 U/10(6) cells at 7 days. A similar inhibitory effect on ALP activity was found after treatment with TGF-alpha. In contrast, ROS cells maintained a high ALP activity (1748 U/10(6) cells) throughout culture, unaffected by EGF. Scatchard analysis demonstrated that PDL fibroblastic cells have both high- and low-affinity forms of EGF-R, while ROS cells did not have any detectable EGF-R. Treatment of PDL cells with Dex for 2 days decreased the synthesis of EGF-R protein, the expression of EGF-R mRNA and the number of EGF-R. In contrast, EGF treatment increased the expression of EGF-R mRNA. These data suggest that PDL fibroblastic cells express numerous EGF-R, but the number decreases during their differentiation into mineralized tissue-forming cells under the influence of Dex. Thus, EGF-R may function in the stabilization of phenotype in PDL fibroblastic cells. PMID- 8368953 TI - Induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1. AB - Osteogenic protein-1 (OP-1, BMP-7), a member of the transforming growth factor beta supergene family, induces cartilage and bone formation when implanted in intra- and extraskeletal sites in vivo. The human OP-1 gene has been cloned and biologically active recombinant OP-1 homodimers (hOP-1) produced. The amount of bone induced by hOP-1 in vivo is related to the amount of protein implanted. Dentine possesses bone morphogenetic protein (BMP) activity. Impure material from allogenic bone with BMP activity induced reparative dentine formation in dogs. The objective of this study was to determine if the amount of reparative dentine stimulated by hOP-1 is related to the amount of protein utilized in direct pulp capping experiments. Freshly exposed molar and premolar pulps were treated with varying amounts of a complex comprising hOP-1 and a carrier matrix of purified bovine type-1 collagen powder (CM) moistened with sterile saline. Reparative dentine was present in all hOP-1/CM treated teeth (12 of 15) that remained sealed for the 6 weeks' healing. Substantially more new dentine was present in teeth treated with hOP-1/CM than in those treated with Ca(OH)2 paste and the amount of reparative dentine formed was proportional to the amount of hOP-1/CM (P < 0.05). No reparative dentine formed in collagen carrier or untreated teeth. The appearances of the new tissue suggested that much of the mass of the hOP-1/CM was replaced first by a pulp-like connective tissue, which mineralized to form reparative dentine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8368954 TI - The effects of outward forced convective flow on inward diffusion in human dentine in vitro. AB - In vitro experiments were conducted to evaluate the influence of outward forced convective flow on the inward diffusion of radioactive iodide. When the smear layer was present, application of 15 cmH2O (1.47 kPa) outward-directed filtration pressure reduced the inward flux of iodide by about 10-20% depending upon the hydraulic conductance of each specimen. When the smear layer was removed by acid etching, the same 1.47 kPa pressure lowered the inward iodide flux by as much as 60%, depending on the hydraulic conductance. The results demonstrate the importance of the balance between inward diffusion and outward bulk-fluid movement on the rate of permeation of exogenous solutes. PMID- 8368955 TI - Electromyographic turns analysis of sustained contraction in human masseter muscles at various isometric force levels. AB - The jaw-closing muscles differ from peripheral limb muscles in that the maximum attainable force does not decline following a sustained isometric contraction. Also, the averaged electromyographic (EMG)/force ratio in these muscles does not change with sustained contraction, whereas it increases in fatiguing limb muscles. The present study analysed EMG records from masseters in healthy male subjects. No statistically significant difference was seen between average rectified EMG signals at the beginning or the end of a sustained isometric contraction at 25-100% of maximum voluntary contraction (MVC). However, when the number of turns, or reversals of direction, was taken at various percentage MVC levels, a significant decrease was seen after 60s or at the end of the contraction. The turns/force ratio decreased monotonically with percentage MVC, but the ratio was not significantly different at the end of a contraction from that at the beginning. This result confirms an earlier suggestion that neuromuscular fatigue does not accompany sustained contractions of these muscles. PMID- 8368956 TI - The association between chewing efficiency and occlusal contact area in man. AB - Chewing is influenced by a number of factors, which include jaw and tongue movements, the activity of circumoral muscles, bite force and hard oral surfaces, but it is not clear which of these factors is most crucial to efficiency. The mere presence of surfaces such as the hard palate, or teeth, does not insure that chewing will be efficient. The purpose of this study was to explore the relationship between occlusal contact area, and chewing efficiency and to observe the influence of chewing-side preference on efficiency. These variables were recorded for both left- and right-hand sides, in a sample of 26 normal young adults. Chewing efficiency was estimated by the size of food particles collected after a predetermined number of chewing strokes. The particles were measured using image analysis and the median size calculated. Comparisons were made, firstly within subjects, between the left- and right-hand side, and secondly between subjects. Correlations were found between chewing efficiency and occlusal contact area which were more pronounced within, than between, subjects. It was concluded that while occlusal contact area influenced chewing efficiency within the same individual, it could not account for the differences in chewing efficiency found between individuals. Differences in the movement of the jaw and in the bite force may have a greater influence on chewing efficiency than occlusal contact area. PMID- 8368957 TI - Effect of dietary vitamin E supplementation and rotational stress on alveolar bone loss in rice rats. AB - The effect of this supplementation on bone loss (distance from the cementum enamel junction to the alveolar crest measured at the midline of the lingual aspect of each of the mandibular molar roots) was studied in rats that were either not stressed or stressed on a rotational device for 90 days. In the first study, neither vitamin E nor stress condition had statistically significant effects but there was substantial bone loss and bone-loss variability in all groups. Before the start of the second study, to reduce differences in bone loss that might otherwise exist before introduction of the treatments, rats received an antibiotic in their drinking water. In addition, rotational stress was introduced more abruptly than in the first study to reduce the likelihood of adaptation. Bone loss and bone-loss variability were substantially reduced in the second study. Analysis of these data indicated that vitamin E supplementation had a statistically significant protective effect, which was most pronounced at sites most susceptible to loss. Stressed subjects tended to lose more bone, but this effect was not significant. These findings suggest some role for vitamin E supplementation in the maintenance of periodontal health but also a sensitivity in this effect to initial periodontal status. PMID- 8368958 TI - An immunohistochemical study of the effects of fluoride on enamel development in the rat incisor. AB - A monoclonal antiamelogenin antibody was used to investigate the effects of fluoride on enamel development in the rat incisor. The results suggested that during secretion the enamel matrix molecules are arranged in such a way as to mask the epitope recognized by the monoclonal antibody. However, during the transition stage of development as the matrix begins to be degraded the epitope becomes exposed and labelling intensity increases to reach a maximum at the end of transition/start of maturation. The effect of fluoride is to delay the appearance of labelling within the enamel matrix until the end of transition. This suggests that the fluoride may inhibit enzymatic degradation or disaggregation of the matrix, the resulting residual matrix then inhibiting crystal growth. PMID- 8368959 TI - Histochemical demonstration of acid phosphatase activity in terminal Schwann cells associated with Ruffini endings in the periodontal ligament of rat incisors. AB - Histochemical staining for acid phosphatase, a marker for lysosomal elements, distinguished rounded, intensely reactive cells from less reactive fibroblasts and osteoblasts in the lingual periodontal ligament. The highly reactive cells were located exclusively in the alveolar half of the ligament. Double staining for acid phosphatase and S-100 protein confirmed that these reactive cells were identical with the terminal Schwann cells associated with periodontal Ruffini endings. Electron microscopically, reaction products for acid phosphatase were observed in the lysosomes and Golgi apparatus in the paranuclear cytoplasm of the terminal Schwann cells. As the terminal Schwann cells associated with the Ruffini endings are assumed to be capable of synthesizing exportable proteins, acid phosphatase in this type of cell may be involved in the processing of macromolecules in synthetic and/or secretory pathways. PMID- 8368960 TI - Histochemical evidence for a cervical plexus contribution to the cat mandibular dentition. AB - The accessory innervation of the mandibular dentition was examined by use of the retrograde transportation of horseradish peroxidase or wheat-germ agglutinin horseradish peroxidase. Nerves within the cervical plexus which contained transported horseradish peroxidase included the great auricular and transverse cervical. Examination of the upper cervical dorsal-root ganglia revealed occasional labelled cells within cervical levels C1, C2, and C3 in approx. 55.6% of the cases. PMID- 8368961 TI - Influence of mastication on saliva, plaque pH and masseter muscle activity in man. AB - An earlier study showed that frequent gum chewing may enhance parotid gland function and reduce the acidogenicity of dental plaque. The aim now was to determine whether these effects would be observed after a 2-week period of diet altered to increase masticatory effort, and secondarily to assess the effects of chewing gum on masseter muscle activity. Ten subjects took part in the first experiment. Saliva was collected before and after the diet change and the plaque pH response to a sucrose challenge was measured. Subjects completed 3-day diet histories and wore electromyographic (EMG) devices to record masseter activity. In the second experiment, 10 subjects wore EMG devices for 3 days to record masseter activity on three daily regimens: baseline (no gum chewing), hourly gum chewing (sugar-free gum chewed for 10 min every hour) and chewing five sticks of gum each for 20 min during the day. Data were analysed by paired t test or repeated-measures analysis of variance. For the first experiment, EMG data indicated significant increases in chewing activity (p < 0.05), although there were no changes in salivary flow rates or the plaque pH response to sucrose. The second experiment showed that total EMG activity increased significantly on both gum-chewing regimens (p < 0.01), the magnitude of the increase being greater for hourly chewing. Overall, masseter EMG activity was increased 41% by diet alteration, compared to increases of 96 and 152% on the five-stick and hourly gum chewing regimens, respectively. PMID- 8368962 TI - Fermentation of carbohydrates in different flours by Streptococcus mutans. AB - The ability of Streptococcus mutans to ferment carbohydrates and to produce acid was investigated in different flours in vitro. The amounts of acid produced suggest a possible ecological role of the tested flours in the occurrence of Strep. mutans in dental plaque. PMID- 8368963 TI - Interactions between denture lining material, protein pellicles and Candida albicans. AB - The interactions between pellicles derived from saliva, serum, mucin and lysozyme deposited on lining material (tissue conditioner) and Candida albicans were investigated by monitoring pH changes associated with protein-free and protein coated lining material and by ultrastructural observations of yeast colonization. No significant differences in pH reduction between culture media in contact with the protein-free, control lining materials and those coated with saliva, serum or mucin were observed after 120 h of incubation. However, scanning electron microscopy revealed that much greater numbers of the yeasts colonized the saliva- or serum-coated lining material than the lysozyme-, mucin-coated or control material. Hyphal invasion was observed in saliva-coated lining material. These results suggested that denture pellicle derived from saliva and/or serum may potentiate candidal colonization of denture lining materials. PMID- 8368964 TI - Sampling ryegrass to assess the risk of annual ryegrass toxicity. AB - Most stock losses caused by annual ryegrass toxicity occur because stockowners unknowingly allow their stock to graze annual ryegrass (Lolium rigidum) infected with the bacterium Clavibacter toxicus. To help stockowners avoid losses we have developed criteria for a testing service to determine the risk of poisoning before the pasture is grazed. Low, medium and high risk categories were selected using samples of dry, mature ryegrass seedheads collected by stockowners from untreated, infected pastures in South Australia. The proportion of toxic paddocks in each risk category over all the seasons tested was 11%, 32% and 76%, respectively, and these accounted for 7%, 14% and 79% of total stock losses. The proportion of paddocks in which stock were poisoned did not vary significantly between years, was not affected by variation in sample weight, and did not vary between South Australia and Western Australia. PMID- 8368965 TI - Use of a modified open patch-graft technique and valvulectomy for correction of severe pulmonic stenosis in dogs: eight consecutive cases. AB - A modified open patch-graft technique was used to correct congenital pulmonic stenosis in 8 dogs. Pulmonary valve dysplasia was moderate to severe in all cases, based upon clinical and echocardiographic criteria, and 3 dogs were in right-sided congestive heart failure at the time of surgery. Seven of the 8 dogs survived the surgery. One surviving dog displayed cerebral cortical dysfunction, the remaining 6 had no detectable neurological sequelae. Right ventricular failure was alleviated in all 7 surviving dogs, but right ventricular dilatation persisted post-operatively. Pulmonary valvulectomy and open patch-grafting provides an effective means of alleviating signs of congestive heart failure caused by pulmonary valve dysplasia, even in the presence of severe infundibular hypertrophy and dynamic outflow obstruction. PMID- 8368967 TI - A study of the microbial flora of the anterior vagina of normal sows during different stages of the reproductive cycle. AB - Sterile guarded swabs were used to sample the anterior vaginal and cervical area of 23 normal healthy sows during various stages of the reproductive cycle. The samples were collected one week before farrowing, within 24 hours of farrowing, weekly up to weaning, at mating and at 2 and 3 weeks after mating, and then plated and incubated aerobically and anaerobically. At least one positive sample was obtained from each sow and at each stage of the reproductive cycle. Most positive samples (78.3%) were obtained on the day of farrowing and the least 3 weeks after mating (19.0%). The second highest number of positive samples (45.5%) was found immediately after mating. Although there was no significant difference among sows of different parities, there was a trend for older sows to have more positive samples after farrowing (84.6%). There was a greater decrease in positive samples after farrowing and after mating among younger sows compared with older sows. A wide range of bacteria including aerobic and anaerobic species, were recovered from 142 isolates. The more representative bacteria were Streptococcus spp (23.2%); Escherichia coli (22.5%); Staphylococcus spp (19.0%) and Corynebacterium spp (13.4%). Of the cultures, 54.7% were pure and 45.3% were mixed. Both the percentage of bacterial isolates as well as the type of culture (pure or mixed) were similar to those frequently reported in clinical cases of vulval discharge syndrome. The results indicate that sows usually develop infections of the reproductive tract at farrowing and mating but these infections do not normally persist. PMID- 8368966 TI - The relationship between the prevalence of uterine lesions and the use of medroxyprogesterone acetate for canine population control. AB - The prevalence of uterine disease was established during desexing of 175 bitches in the Torres Strait and Cape York, 42 of which had been treated with injectable medroxyprogesterone acetate (MPA) for oestrus postponement. The prevalence of uterine lesions was 45% for treated bitches, 5% for untreated bitches, and 14.9% for the sample population. A highly significant relationship (P < 0.01) between MPA treatment and uterine lesions was established. A significant association (P < 0.05) between age (> 2 years old) and uterine lesions was found, most likely attributable to a significantly higher proportion (P < 0.01) of MPA-treated bitches in the older population. There was no significant difference in the effect of MPA on the prevalence of uterine lesions between older and younger bitches. There was no effect of parity on the prevalence of uterine lesions. PMID- 8368969 TI - Mycobacterium bovis infection in a goat. PMID- 8368968 TI - Studies on preweaning piglet diarrhoea. AB - The aim of this study was to determine the cause and risk factors involved in preweaning piglet diarrhoea. Faecal samples from 2380 diarrhoeic piglets, 5 to 30 days of age, were examined for enteropathogens. Isospora suis oocysts were detected in 53.8% of samples, Escherichia coli in 18.2% and rotavirus in 16.9%. I suis had the widest distribution, being present on 70.9% of 151 piggeries. The onset of diarrhoea occurred mainly between 7 and 14 days (77.5%), peaking at 10 days. Records of 4086 litters from two intensive piggeries were analysed and showed no seasonal variation or effect of sow parity on the incidence of piglet diarrhoea. I suis was the most common enteropathogen associated with diarrhoea in piglets from 5 days of age until weaning. PMID- 8368970 TI - Inhibitory effect of heparin on Rhabdovirus and Bunyavirus isolated from cattle. PMID- 8368971 TI - Comparative efficacy of moxidectin, an ivermectin/clorsulon combination and closantel against immature paramphistomes in cattle. PMID- 8368972 TI - Congenital lymphoedema in a Brahman calf. PMID- 8368973 TI - The camel, Camelus dromedarius, as a host of the cattle tick, Boophilus microplus. PMID- 8368974 TI - Observations on the endo- and ectoparasites affecting dogs and cats in aboriginal communities in the north-west of Western Australia. PMID- 8368975 TI - Spirurid nematodes in dogs and cats from central Australia. PMID- 8368976 TI - A puppy death and Amanita phalloides. PMID- 8368977 TI - Correlations between ultrasonography findings and hormonal profiles at oestrus in pure Spanish breed mares. PMID- 8368978 TI - A survey of Western Australian dogs for Sarcocystis spp and other intestinal parasites. PMID- 8368979 TI - Import of horses from Europe: an insect-proof container. PMID- 8368980 TI - Incidence of cardiac dysrhythmias occurring during centrifuge training. AB - High-G training has been reported to provoke dysrhythmias in many subjects. These reports have been based on small subject groups. Students attending aeromedical professional courses at the USAF School of Aerospace Medicine are offered the opportunity to participate in high-G centrifuge training on the Armstrong Laboratory centrifuge, during which ECG monitoring is routinely performed. This study documents the incidence of dysrhythmias in this large group of subjects. The pertinent information from the records of 1,180 training sessions from 1984 91 were transcribed to a database on a personal computer. Dysrhythmias were recorded in 552 (47%) of the training sessions. Ventricular ectopy occurred in 480 (41%) of the sessions, and supraventricular dysrhythmias appeared in 127 (11%). In 53 (4.5%) of the sessions, training either was or would have been terminated because of the dysrhythmia. Session-terminating dysrhythmias included: 26 ventricular tachycardias (2.2%), including 18 triplets (1.5%); 9 ventricular couplets (0.8%); 8 episodes of too-frequent ventricular premature beats (0.7%); 4 of supraventricular tachycardia (0.3%), including 2 with aberrant conduction (0.2%); 2 of aberrantly conducted beats (0.2%); and 4 of anomalous bradycardia (0.3%). Centrifuge training can provoke serious dysrhythmias in ostensibly healthy individuals, and ECG monitoring of aircrew undergoing such training is recommended for their safety. Because some of these dysrhythmias are disqualifying for aircrew duties, the need for a more lenient aeromedical disposition policy must be considered. PMID- 8368981 TI - Degeneration of cervical intervertebral disks in fighter pilots frequently exposed to high +Gz forces. AB - This study investigated the occurrence and the degree of cervical disk degeneration among senior fighter pilots frequently exposed to high +Gz forces, compared with nonexposed controls matched for age and sex. A resistive magnetic resonance (MR) scanner operating at 0.1 T was used to image the cervical intervertebral disks. Sagittal MR images were obtained and disk degeneration was graded 0-6. Both the occurrence and the median degree of disk degeneration were greater among the pilots than among the controls. The greatest difference in the occurrence of disk degeneration (grades 1-6), which also reached statistical significance, was detected for the C3-4 disk: 88% among the fighter pilots and 64% among the controls, respectively. With respect to the moderate degenerative changes (grades 3 and 4) in the C3-4 disk, the difference in the occurrence (88% vs. 36%) was again statistically significant. There was no difference between the other disks. The median disk degeneration between the groups differed (2.0 vs. 1.0), the difference being the most remarkable (3.0 vs. 1.0) for the C3-4 disk. The differences in the median disk degeneration were also statistically significant. These findings suggest that frequent exposure to high +Gz forces may cause premature disk degeneration. PMID- 8368982 TI - The time-course of alcohol impairment of general aviation pilot performance in a Frasca 141 simulator. AB - This study examined the time-course of alcohol impairment of general aviation pilot simulator performance. We tested 14 young (mean age 25.8 years) and 14 older (mean age 37.9 years) pilots in a Frasca 141 simulator during alcohol and placebo conditions. In the alcohol condition, pilots drank alcohol and were tested after reaching 0.10% BAL, and then 2, 4, 8, 24, and 48 h after they had stopped drinking. They were tested at the same times in the placebo condition. Alcohol impaired overall performance. Alcohol impairment also depended on the order in which subjects participated in the alcohol and placebo sessions, with larger decrements for the alcohol-placebo order than for the opposite order. To examine the influence of alcohol independent of session order effects, we compared performance in the first alcohol session with performance in the first placebo session. This analysis showed that alcohol significantly reduced mean performance in the alcohol condition at 0.10% BAL and at 2 h. In addition, alcohol increased variability in performance in the alcohol session from 0.10% BAL to 8 h, suggesting that some subjects were more susceptible to alcohol than others. Older pilots tended to perform some radio communication tasks less accurately than younger pilots. PMID- 8368983 TI - Spatial contrast sensitivity through aviator's night vision imaging system. AB - Visual acuity is often used to assess vision through image intensifying devices such as night vision goggles (NVG's). Fewer attempts have been made to measure contrast sensitivity through NVG's. Such information would be useful to better understand contrast processing through NVG's under various stimulus conditions. In this study, computer-generated letter charts were used to measure contrast sensitivity through third generation NVG's for a range of letter sizes. The red phosphor of a standard color monitor proved to be an effective stimulus for third generation devices. Different night sky conditions were simulated over a 3 log unit range. The results illustrate the profile of contrast sensitivity through third generation NVG's over a range of night sky conditions. Comparison of measurements through NVG's to measurements obtained without the device but at the same luminance and color distinguish between effects of luminance and noise on contrast sensitivity. PMID- 8368984 TI - Some personality and aptitude characteristics of air traffic control specialist trainees. AB - This study examined the interrelations of personality traits, aptitude test scores, and job performance self-expectations as predictors of success in the FAA Academy screening program of prospective air traffic controllers. Based on the State-Trait Personality Inventory (STPI), men and women Air Traffic Control Specialist (ATCS) trainees exhibited less anxiety and anger than normative groups of college students and Navy recruits. ATCS pass rates for 1,284 entrants were lower within each aptitude test score level for the subjects with anxiety or anger scores above the normative levels. Analyses indicated significant relationships between self-expectations of future job performance and both anxiety and aptitude test scores. Personality factors were found to affect the predictive validity of the primary test used for determining a student's aptitude for learning air traffic control principles and procedures. PMID- 8368985 TI - The effects of Benadryl and Hismanal on mood, physiological measures, antihistamine detection, and subjective symptoms. AB - The majority of antihistamines have sedative effects; however, it is claimed that Hismanal (astemizole) does not possess central nervous system side effects. A three-factor, repeated measures, double-blind design was used to compare the effects of singl oral doses of 1) Benadryl (diphenhydramine), 50 mg; 2) Hismanal, 10 mg; and 3) placebo, on two mood scales, physiological measures, sleepiness, the ability to detect ingestion of an antihistamine versus placebo, and symptoms in 28 healthy men. Higher tension, greater fatigue, and lower activity levels were reported post-Benadryl (p < 0.05). Lower vigor-activity and higher confusion bewilderment post-Hismanal and Benadryl were noted 1 h postingestion (p < 0.05), with confusion being lower and activity higher for Hismanal than for Benadryl (p < 0.05). Low vigor-activity, high confusion, and increased sleepiness post Benadryl persisted for 3 h, while fatigue-inertia persisted for 7 h (p < 0.05). Results suggest that Hismanal is superior to Benadryl for avoidance of subjective effects; however, neither antihistamine was entirely devoid of subjective effects. PMID- 8368986 TI - The effects of Benadryl and Hismanal on psychomotor performance and perceived performance. AB - Classic antihistamines (H1 antagonists) have sedative effects and can impair psychomotor performance. It is claimed that Hismanal (astemizole) does not possess central nervous system side effects. A three-factor, repeated measures, double-blind design was used to compare the effects of single oral doses of (1) Benadryl (diphenhydramine)-50 mg, (2) Hismanal-10 mg, and (3) placebo on a battery of 11 cognitive information-processing tasks and performance ratings in 28 healthy men. Performance decrements were seen at 1 h post-Benadryl ingestion on Following Directions (p < 0.05), at 1.5 h on Unstable Tracking (p < 0.05), and at 3 h on serial addition/subtraction (p < 0.05). No decrements in performance were found post-Hismanal. Subjects perceived their performance as poorer following Benadryl ingestion versus placebo and Hismanal for 3 h postingestion (p < 0.05). Results demonstrate performance effects post-Benadryl ingestion for 1 h longer than previously reported. Tasks which demonstrated sensitivity to antihistamines were those which required an element of sustained attention and those which required a visual-motor response. PMID- 8368987 TI - Prediction of maximal oxygen uptake from submaximal exercise testing in aerobically fit and nonfit men. AB - Aerobic physical fitness, as determined by the body's maximal capacity to utilize oxygen (VO2max) during demanding work, is an important determinant of a person's ability to perform many military tasks. The present 2.4 km (1.5 mi) run has not proven itself capable of accurately estimating this important factor on a periodic basis. This paper reviews prior studies of heart rate response to known workloads on a cycle ergometer to estimate VO2max. This submaximal test, as revised by scientists at the USAF Armstrong Laboratory at Brooks AFB, TX, was validated on 22 male subjects by comparing the test results with laboratory measurements of VO2max obtained by analysis of expired air during maximal treadmill exercise. Two groups of subjects were selected; one consisting of highly trained runners and the other of inactive subjects who did not perform regular aerobic exercise. The cycle ergometry prediction underestimated measured VO2max by 8.1 ml.kg-1 x min-1 (SEE = 4.25) in all subjects, but there was a correlation of 0.95 between the estimated and measured values. Both estimated and measured VO2max were significantly higher in the group of trained runners than in the inactive subjects. PMID- 8368988 TI - Risk assessment and clinical aeromedical decision-making. AB - This article presents a format of aeromedical decision-making used in neurology cases referred to a U.S. Navy Special Board of Flight Surgeons (SBFS) from 1988 to 1990. The format consists of a series of questions addressing aeromedical concerns, an aeromedical disposition flowchart, and a decision analysis tree. Decision Analysis is a tool used in clinical medicine to assist decision-making under conditions of uncertainty. The Decision Analysis approach may be applied to complex aeromedical disposition questions that face flight surgeons. The concept of risk assessment as it applies to decision-making and aeromedical disposition is discussed. The outcome of 24 neurology cases referred for aeromedical disposition are presented. PMID- 8368989 TI - Mortality experience of cockpit crewmembers from Japan Airlines. AB - The purpose of this study was to evaluate the long-term mortality and causes of death among cockpit crewmembers. A total of 2,327 cockpit crewmembers registered at Japan Airlines between August 1, 1952, and December 31, 1988, were traced to assess mortality. Medical records were also reviewed. The mortality rates for the cockpit crewmembers were compared to those for the general Japanese population using standardized mortality ratios (SMR's). As of December 31, 1988, 59 (2.5%) of 2,327 individuals were deceased, and the leading causes of death were accidents, malignant neoplasms, and cardiovascular diseases. The overall mortality rate for the cockpit crew was significantly lower than the national standard (SMR = 0.66, p < 0.001; 95% C.I. 0.50-0.85). However, marked differences were found in cause-specific mortality, where mortality due to accidents was significantly increased (SMR = 2.43, p < 0.001; 95% C.I. 1.63-3.50), while deaths from cancer were similar, and those for cerebral vascular accidents (CVA) and coronary artery disease (CAD) were lower than comparable rates for the general population. We conclude that cockpit crewmembers had a better total mortality experience compared to the general Japanese population, except for deaths due to accidents. PMID- 8368990 TI - Acute hypertensive response to +Gz acceleration in mildly hypertensive pilots. AB - Two fighter pilots with mild hypertension and a mildly hypertensive response to exercise underwent ambulatory blood pressure monitoring during a routine flight that included a brief exposure to +4 Gz stress. They exhibited an acute elevation of both systolic and diastolic blood pressures during +4 Gz stress: from 140/90 and 135/90 mm Hg to 179/139 and 180/140 mm Hg, respectively. Heart rate reached 182 and 132 beats/min. These responses of hypertensives may reflect exaggerated baroreceptor and sympathetic responses which cause a pronounced over-shoot of blood pressure. The findings demonstrate the value of 24-h ambulatory blood pressure monitoring for documenting episodic elevations of blood pressure that do not influence the "normal" average blood pressure, but may nevertheless have important clinical implications. PMID- 8368991 TI - Fatal mishap report: first SPH-4B flight helmet recovered from a U.S. Army helicopter mishap. AB - The most common cause of death in helicopter accidents is head injury. Flight helmets can be designed to distribute and attenuate crash forces to the head. Experience derived from crashes using the U.S. Army SPH-4 flight helmet has led to modifications to improve protection. Within the past year, the Army has introduced the SPH-4B flight helmet which includes several new features to reduce injury in future mishaps. The first SPH-4B flight helmet recovered from a fatal mishap is described and correlated with the injuries to the wearer. The new shell and liner reduced the impact forces to the head. There were no side impacts to determine the performance of the crushable earcups in the helmet. The new SPH-4B flight helmet has several new and distinctive features that should improve survival in future helicopter crashes. Careful study of life support equipment retrieved from crashes is important to understand how the equipment performs in the crash environment. PMID- 8368992 TI - Monitoring core temperature during exercise: ingestible sensor vs. rectal thermistor. AB - A telemetry monitoring system using an ingestible temperature sensor has recently become available commercially, but to our knowledge no published data on exercise applications have been reported. Consequently, core temperature was measured by both ingestible capsule sensors and standard rectal thermistors in six trained subjects (three cyclists, three runners) during 30 to 90 min of progressive cycling or treadmill exercise. Testing was conducted 3-9 h after ingestion of the capsule. The telemetered temperature was lower than the rectal temperature both at rest and during exercise in every subject, with resulting significant (p < 0.005) mean differences (+/- S.D.) of 36.91 (+/- 0.41) vs. 37.50 (+/- 0.21) and 38.01 (+/- 0.33) vs. 38.94 degrees C (+/- 0.24), respectively. The mean temperature difference increased by 58% from rest (0.59 degrees C) to peak exercise (0.93 degrees C). These preliminary findings demonstrate a consistently lower temperature from the capsule sensor located within the GI tract compared to rectal thermistors. Replication of these results and investigation into this disparity are necessary before these ingestible capsules should be used for routine monitoring of core temperature. PMID- 8368993 TI - Aerospace Medical Association, Directory issue. PMID- 8368994 TI - [Clinical laboratory diagnosis in swine practice]. AB - Necessity and facilities of clinical laboratory diagnostics in veterinary swine practice are discussed. The selection of suitable tests with regard to diagnostic relevance and reliability is pointed out. Typical test features (sensitivity and specificity) as well as disease dependent parameters (prevalence, positive or negative predictive value) are presented and illustrated by means of urinary tract infections in sows. It is concluded that a specific selection of tests and probands closely related to diagnosis is more successful than the use of unspecific multi-analysing procedures (profile tests). PMID- 8368995 TI - [The treatment of Eubacterium suis infections in boars]. AB - The main habitat of Eubacterium suis (E. suis) is the preputial diverticulum of male pigs. E. suis can be transmitted from boars to sows at the time of mating, and ascending urinary tract infections (cystitis and pyelonephritis) in sows may develop. In this paper different methods of treatment were investigated to eliminate E. suis from the diverticulum of carrier boars (n = 33). Local therapy and feed medication were administered separately or in combination. For local instillation into the preputial sac penicillin, penicillin/streptomycin or enrofloxacin were used, while medicated feed contained enrofloxacin. None of the treatments resulted in boars, which were persistently free from E. suis. Also additional hygiene measures as washing of boars and disinfection of pens could not improve the results. At the latest 18 days after treatment E. suis could be detected again in the preputial diverticulum of all boars. Short duration of action of antibiotics in the preputial sac as well as re-colonisation of the diverticulum by contaminated pens are discussed. In herds in which urinary tract infections are troublesome it is worthwhile using artificial insemination to prevent transmission of E. suis to the sow. Treatment of unspecific urinary tract infections in sows may be also important, because alterations of bladder mucosa due to other bacteria may support the colonisation of E. suis. PMID- 8368996 TI - [Prevention of myopathies and cardiomyopathies in swine using magnesium aspartate hydrochloride]. AB - The efficiency of magnesium-aspartate-hydrochloride (MAH) in prophylaxis of porcine stress-induced myopathy was investigated. For the examination a conveyor belt was used. MAH was administered orally or intramuscularly. Clinical investigations, blood specimen collections and ECG were carried out before and after running. Stress-induced tachypnoea and tachycardia and hyperthermia were reduced after both forms of administration of MAH. The enzyme activity of CK, LDH and alpha-HBDH increased slighter after oral and i. m. application. The increase of serum glucose concentration as well as serum lactate level were reduced after oral and i. m. substitution with MAH. In the ECG apart from the relative diastolic period all time values were significantly prolonged after MAH substitution. The results indicate that several stress-induced changes of clinical and metabolic parameters can be reduced by administration of MAH. PMID- 8368997 TI - [New methods of veterinary care for swine herds]. AB - In hybrid breeding schemes it is important to make sure that no diseases are transferred from the multiplier farms to the piglet producers. In the German Federal Hybrid Scheme (BHZP) are 280 multiplier farms working with Personal Computers with the same software. The software helps the veterinarians in analysing health problems in the herds. Some data-evaluations of piglet losses, herd performance-traits and causes of sow-losses are shown. Because of the identical software in all farms is it possible to work with the same vaccine strategy in the whole breeding scheme. The results of the data-evaluations are the main basis for the farmer, veterinarian and adviser. PMID- 8368998 TI - [Clinical indications of an auxiliary effect of antihistamines (parenteral benadryl) in the treatment of RSV infections of cattle]. AB - The BRSV-infection belongs to the Bovine Respiratory Disease (BRD) complex. Because of its clinical features as well as pathomorphological and histopathological lesions it can be considered an independent disease. Therefore, concepts of treatment deviating from conventional BRD have to be applied. In addition to antibiotic therapy, therefore, the effect of treatment with the antihistamine Diphenylhydramin (Benadryl-parenteral, Parke Davis) was checked. For the evaluation the internal body temperature was used as measure. With the additional daily application of the antihistamine to the antibiotic therapy the animals were faster without fever. The difference was significant. PMID- 8368999 TI - [Hemorrhagic enteropathies in fattening swine]. AB - It is reported on 34 fattening pigs with hemorrhagic enteropathy or blood in the intestine, which were submitted for necropsy to the Veterinary Ambulance Schwarzenbek. Only those animals were included in this study, which had lesions in the small intestine or small and large intestine. Cases of swine dysentery with the lesions being restricted to the large intestine were not considered here. No common cause of hemorrhagic enteropathy was found. In four cases there was an intestinal torsion. In one animal the blood in the intestine originated from a gastric ulcer. On 25 of the 34 pigs further examinations could be done. Of those, enteropathogenic E. coli were isolated in 13 cases, with two of the animals having a mixed infection of two serotypes each. Cl. perfringens was found in two cases and S. hyodysenteriae in four cases. In one pig S. typhimurium was isolated from the mesenteric lymph nodes and in one animal the proliferative hemorrhagic form of the adenomatosis-complex was diagnosed. Histopathologically Campylobacter-like organisms were found in epithelial cells of crypts in the small intestine. PMID- 8369000 TI - Enantiomeric aspects of the metabolism of mianserin in rats. AB - After separate administration of mianserin (CAS 24219-97-4) enantiomers to rats, the hydroxy-metabolites of S-mianserin were excreted mainly as conjugates whereas the amount of free phenolic metabolites was greater after administration of the R enantiomer. The sulphate-conjugate of 8-hydroxy-mianserin was stereoselectively found in faeces only after administration of S-mianserin. Based on in vitro experiments with sulphatase, the stability of this conjugate towards enzymic hydrolysis appears a likely explanation. In vitro experiments with liver homogenates of rats revealed little enantioselectivity with respect to oxidative metabolism. After prior enzyme induction with phenobarbital, however, enantioselectivity with regard to N-oxidation was found. The 3-oxo-mianserin metabolite, found in vitro, is most likely the product of a rearrangement of mianserin-N-oxide. N-formyl-demethyl-mianserin, identified in vitro, is considered to be an artefact. PMID- 8369001 TI - Effect of the rice bran-derived phytosterol cycloartenol ferulic acid ester on the central nervous system. AB - In order to investigate the effect of cycloartenol ferulic acid ester (CFE, CAS 21238-33-5), a component of gamma-oryzanol which is a phytosterol derived from rice bran, on the central nervous system, a variety of pharmacological tests were performed. It was shown that CFE had a suppressant effect on the central nervous system, but its properties were different from those of existing major and minor tranquilizers. In addition, its efficacy in several models of cerebral dysfunction was demonstrated. Since any clear effects could not be obtained under the treatments with gamma-oryzanol, CFE seems to be more useful than gamma oryzanol. Thus the results of this study suggest that CFE may serve as a new plant-derived cerebral activator possessing a wide range of pharmacological actions. PMID- 8369002 TI - In vitro and in vivo electrocardiographic evaluation of the novel calcium antagonist monatepil on cardiac conduction system. AB - Effects of monatepil ([(+/-)-N-(6,11-dihydrodibenzo[b, e]thiepin-11-yl)-4-(p fluorophenyl)-1-piperazinebutyramide]m aleate, AJ-2615, CAS 103377-41-9), a novel calcium antagonist, on the cardiac conduction system were compared by electrocardiography with those of the existing calcium antagonists (diltiazem, verapamil and nifedipine) in isolated rabbit heart preparations in vitro and in anesthetized and conscious dogs in vivo. Monatepil (10(-7) mol/l) prolonged the atrio-His bundle conduction time (AH interval) in the Langendorff perfused rabbit heart, like diltiazem, verapamil and nifedipine. This prolongation was decreased to 1/10 in the presence of 3.6% bovine serum albumin. In anesthetized dogs, monatepil (0.1-1.0 mg/kg i.v.), unlike diltiazem and verapamil, did not prolong AH interval. In conscious dogs, monatepil even at 100 mg/kg p.o. did not affect electrocardiograms. At the high dose of 300 mg/kg p.o., only a slight prolongation of the QT interval was found, but the QTc interval was not affected. Diltiazem at 10 mg/kg p.o. caused a prolongation of the PR interval and a disappearance of QRS waves. In conscious renal hypertensive dogs, repeated administration of monatepil (10 mg/kg/d p.o. for 29 days) had little effect on the conduction system of the heart examined by electrocardiograms, albeit a persistent fall in blood pressure continued throughout the administration period. The above results suggest that monatepil is a highly safe drug in the treatment of hypertension. PMID- 8369003 TI - General toxicity of the new calcium antagonist felodipine in dogs. AB - Felodipine 4-(2,3-dichlorophenyl)-1,4-dihydropyridine-2,6-dimethyl-3,5- dicarboxylic 3-ethyl ester and 5-methyl ester, CAS 72509-76-3) is a new selective calcium antagonist for use in the management of hypertension or other cardiovascular disease, which requires reduction of peripheral vascular resistance. A combined 6- and 12-month study in dogs has been performed as a part of the preclinical safety program. 30 dogs, 5 males and 5 females per group, were treated with felodipine for 12 months. Additional 18 dogs, 3 males and 3 females per group, were interim-sacrificed after 6-month treatment. The dose levels were 2 x 0.38, 2 x 1.2 and 2 x 2.3 mg/kg daily. Initially, 2 x 3.8 mg/kg/d was used as a high dose. At this dose level 2 animals died preterminally after 4 days of dosing. They were replaced and the high dose level was reduced. Two similar control groups were given a placebo formulation for 12 and 6 months, respectively. All animals were treated b.i.d. using a 4-h time interval. Mucosal hyperemia and tachycardia, as an expression of the vasodilating properties of felodipine, were observed in a somewhat variable but dose-related manner. Noninflammatory gingival hyperplasia, similar to that after treatment with phenytoin and the calcium antagonist nifedipine, occurred with a propensity for the males after 12 months of treatment. Slight-degree gingival hyperplasia was also noted after 6 months of treatment. This change occurred dose- and time related in the medium and high dose groups but was absent in the low dose group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369004 TI - Steady state kinetics of a fatty alcohol-based slow-release nifedipine for once a day application. AB - The linearity of the relationship between dose and plasma concentration of nifedipine has been investigated in healthy male and female subjects under steady state conditions following application of a fatty alcohol matrix slow release nifedipine (Aprical long, CAS 21829-25-4) formulation at a dose rate of 60, 90 and 120 mg once daily. Plasma concentrations showed a broad plateau associated with mean residence times exceeding 20 h. On Day 4 mean pre-dose nifedipine concentrations were 20.5, 24.9, 31.8 ng/ml and Cmax values were 42.3, 51.7 and 93.9 ng/ml for the 60, 90 and 120 mg dose, respectively (n = 15). After dose normalisation there was no significant difference (Wilcoxon matched pair test) in the mean AUCs. Adverse reactions, mainly headache and flushes, were observed at all dose levels but the frequency was not dose-dependent. In view of the demonstrated proportionality between dose and AUC and the long duration of the plateau plasma concentrations it is concluded that this slow release formulation is suitable for once daily administration at dose rates up to 120 mg daily. PMID- 8369005 TI - Evaluation of pharmacokinetics, bioavailability and dose linearity of diltiazem in healthy volunteers. AB - The objective of this randomized five-way cross-over study with healthy male volunteers was to determine, one the one hand, the bioavailability and main pharmacokinetic parameters of 4 sustained release diltiazem (Surecaps, CAS 42399 41-7) test preparations with ascending doses (180, 240, 300, 360 mg), administered as single application, versus an immediate release 60 mg diltiazem reference preparation, which was given thrice a day at 8-h intervals. On the other hand, the study also allowed the evaluation of a possible dose linearity of the test substance diltiazem. Plasma concentrations of diltiazem and its major metabolite desacetyl-diltiazem were measured by high pressure liquid chromatography (HPLC) up to 48 h after single dosing of the sustained release preparations as well as after repeated doses of the immediate release formulation. The undesired side effects/concomitant symptoms observed are known to occur after diltiazem administration. For the area under the curve, e.g. calculated from time 0 to the last quantifiable sample (AUC0-Tlast), the study revealed for the parent compound diltiazem mean values of 926.2, 1602.4, 1873.2 and 2415.7 h.ng/ml after administration of the 4 sustained release test preparations, respectively; for the immediate release reference preparation the value was 1007.2 h.ng/ml. Concerning the main metabolite desacetyl-diltiazem the corresponding values for the 4 sustained release formulations were 138.6, 236.9, 280.2 and 345.6 h.ng/ml, respectively. The corresponding value for the immediately release formulation was 127.5 h.ng/ml. Concerning a possible dose linearity of diltiazem, statistical analysis revealed a convincing linear relationship between at least 3 of the 4 sustained release preparations, therefore linearity may be assumed between 240 and 360 mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369006 TI - Pharmacokinetics of glycerol administered orally in healthy volunteers. AB - Of the three standard osmotherapeutics glycerol, mannitol and sorbitol, glycerol (CAS 56-81-5) alone can be applied orally. As only limited pharmacokinetic data after oral administration are available, studies were performed in 10 healthy subjects (2 female, 8 male, body weight 58-90 kg, age 23-47 years). After 12 h of fasting the subjects drank a single dose of 1.2 g/kg glycerol (Glycerol 85% DAB 9, flavoured with lemon juice). For the first 90 min venous blood was sampled every 15 min, for the following 6.5 h every 30 min. Glycerol serum concentrations were determined by an enzymatic procedure. Intestinal absorption was rapid. Maximum glycerol serum levels ranging from 1285-2238 mg/l (median = 1770 mg/l) were observed 1-2 h after ingestion. On the assumption of full intestinal absorption total body clearance was 0.18-0.26 l/h.kg, and the apparent volume of distribution 0.18-0.34 l/kg. The terminal elimination half-life ranged from 0.61 1.18 h. The concentration-time curves were not adequately described by linear pharmacokinetic models. In all subjects glycerol serum concentrations were high enough to induce increases of serum osmolality of at least 10 mosmol/kg. No signs of haemolysis or haemodilution were observed. PMID- 8369007 TI - Effect of a protein-free dialysate from calf blood on human monocyte differentiation in vitro. AB - Solcoseryl is a protein-free, standardized dialysate/ultrafiltrate derived from calf blood, which has been shown to improve situations of impaired healing in both experimental animals and man. Its activity seems to be multifactorial although the precise cellular and molecular mechanisms contributing to its effect have not been fully elucidated. Since monocyte-derived macrophages play a central role in inflammation and particularly in wound healing and tissue remodelling, the effect of the dialysate on human monocytes cultured in vitro for 10 days in the presence of human serum was studied. The results show that the drug, at concentrations ranging from 0.2 to 2%, increases the cell density of the cultures and the cell protein content, and favours the differentiation of monocytes into macrophages when 1% serum concentration is used in the culture medium. These effects are no more apparent when the serum concentration was raised to 10%. These data suggest that the drug may substitute, at least in part, for serum in monocyte-macrophage cultures. The observed effects give a sound basis for at least a partial explanation of the therapeutic effects of the drug, particularly at sites where the supply of serum-derived factors is limited. PMID- 8369008 TI - [Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double blind study]. AB - The efficacy of a Vitex agnus castus preparation (Strotan capsules) was investigated in a randomized double blind study vs. placebo. This clinical study involved 52 women with luteal phase defects due to latent hyperprolactinaemia. The daily dose was one capsule (20 mg) Vitex agnus castus preparation and placebo, respectively. Aim of the study was to prove whether the elevated pituitary prolactin reserve can be reduced and deficits in luteal phase length and luteal phase progesterone synthesis be normalized. Blood for hormonal analysis was taken at days 5-8 and day 20 of the menstrual cycle before and after three month of therapy. Latent hyperprolactinaemia was analysed by monitoring the prolactin release 15 and 30 min after i.v. injection of 200 micrograms TRH. 37 complete case reports (placebo: n = 20, verum: n = 17) after 3 month of therapy were statistically evaluated. The prolactin release was reduced after 3 months, shortened luteal phases were normalised and deficits in the luteal progesterone synthesis were eliminated. These changes were significant and occurred only in the verum group. All other hormonal parameters did not change with the exception of 17 beta-estradiol which rouse up in the luteal phase in patients receiving verum. Side effects were not seen, two women treated with the Vitex agnus castus preparation got pregnant. The tested preparation is thought to be an efficient medication in the treatment of luteal phase defects due to latent hyperprolactinaemia. PMID- 8369009 TI - Synthesis and pharmacological evaluation of a novel series of alpha-picolinium hydrazone analogues with anticipated antidiabetic activity. AB - A new series of substituted alpha-picolinium p-dimethylaminobenzalhydrazine derivatives and their o-hydroxy analogues has been prepared for evaluation of their efficacy as potential hypoglycemic agents. The synthesis was achieved by condensation of N-amino-alpha-picolinium perchlorate derivatives with the corresponding aromatic aldehydes. The structure of the synthesized products was inferred from elemental and spectral data. The hypoglycemic effect, antimicrobial activity and toxicity of the hitherto and possibly new chemotherapeutic agents were evaluated. Based on screening data, a possible structure-activity relationship has been discussed. PMID- 8369010 TI - [Pharmacokinetics and relative bioavailability of iron and folic acid in healthy volunteers]. AB - The pharmacokinetics and the relative bioavailability of iron and of folic acid was investigated in a randomized, balanced 2-way cross-over study with 14 healthy male participants. The drugs were given in a combined preparation dragee (Ferro Folsan) containing 100 mg of ferrous-II-sulfate x 1.5 H2O (CAS 13463-43-9) and 0.85 mg of folic acid (CAS 59-30-3). Other established preparations were used as reference drugs. All subjects had a normal iron body level and were brought to a saturated folic acid level prior to the investigation. After administration of 2 dragees of the test medication and determination of serum iron level until 9 h p.a., a relative bioavailability of 64%, compared to an equal dose of a ferrous II-sulfate-ascorbic acid reference solution, was calculated. From the serum folate AUC (0-9 h) the relative bioavailability was evaluated with 97% for the oral formulation compared to the i.m. administration. The ratio of the cumulative renal folate excretion in the 0-9 h interval amounted to 76% for the oral compared to the i.m. administration. However, in order to understand this differing result it should be kept in mind that during the first hours following parenteral administration a greater amount of the unchanged compound is renally excreted than after oral dosing. This is presumably based upon the different rate of absorption following both administrations with a steeper absorption phase following the parenteral dose. PMID- 8369011 TI - Investigations of indomethacin-induced gastric ulcer in rats. AB - The pathogenesis of non-steroidal anti-inflammatory drugs (NSAIDs)-induced ulceration is still not completely understood, but it is possible that these effects are associated with a cytoprotective prostaglandin deficiency. Visible marks of gastric mucosa erosions induced by 25 mg/kg indomethacin in rats were determined parallel with the changes of PGE2, PGI2, TxA2 and leukotrienes content in gastric mucosa at various intervals. Beside the decreased level of the so called cytoprotective prostaglandins caused by the inhibition of cyclooxygenase enzyme an overproduction of 5-lipoxygenase products (leukotrienes) was also found. To investigate the hypothesis that the gastric damage caused by NSAIDs is due not only to the decreased level of cyclooxygenase products but to the increased level of lipoxygenase products as well, different lipoxygenase inhibitors and leukotriene antagonists were tested. A lipoxygenase inhibitor and the structurally similar phenidone inhibited the ulcerogenic effect of indomethacin at the same high dose range. The selective lipoxygenase inhibitor nordihydroquaiaretic acid and dual inhibitors can reduce the severity of ulcer formation in lower concentrations as well. The first specific antagonist of SRS-A and a potent and selective antagonist of LTD4 produced a significant gastroprotective effect at i.p. treatment only at high doses. All of these results suggest that an overproduction of leukotrienes and other lipoxygenase products, following cyclooxygenase blockade induced by NSAIDs, may play a role in the development of gastric mucosal damage. PMID- 8369012 TI - Influence of ofloxacin on chloroplasts and mitochondria in Euglena gracilis. AB - Ofloxacin (CAS 83380-47-6), a representative of new quinolones, which exerts inhibitory activity against DNA gyrase in bacteria, damages both semiautonomous organelles in Euglena gracilis: chloroplasts and partly mitochondria. The action of ofloxacin on these organelles was analysed by transmission electron microscopy. The first symptoms of ofloxacin treatment were mass aberrations of chloroplasts with subsequent diluting out of these pathological organelles from the cells, so giving rise to the heterotrophic mutants. The loss of chloroplasts is hereditary. Changes in ultrastructure of mitochondria were observed too. Cup like (in sections ring-like) mitochondria represented the most frequent abnormalities of these organelles induced by the drug. After repeated subcultivations on ofloxacin-free media the number of damaged mitochondria gradually decreased to the normal. PMID- 8369013 TI - Effects of the combination of ketoconazole and calcium channel antagonists against Candida albicans in vitro. AB - Susceptibility of 66 strains of Candida albicans from patients were tested against ketoconazole (Ktz, CAS 65277-42-1), cinnarizine (Cin), verapamil (Ver), nifedipine (Nif), nimodipine (Nim) and the combination of Ktz with these calcium channel antagonists, using Sabouraud's broth. Minimal inhibitory concentrations (MICs) determined on diagnostic plates gave values of Ktz: 34.5 +/- 3.9 micrograms/ml, Cin 413 +/- 11.3 micrograms/ml, Ver 334 +/- 11.4 micrograms/ml, Nif 374 +/- 19.3 micrograms/ml and Nim 486 +/- 20 micrograms/ml. The combination of Ktz and calcium channel antagonists in various ratios (1 : 1, 1 : 2, 2 : 1) was found to exert synergistic effect and the mean values of the combinations were: Ktz+Cin 6.52 +/- 1.67, 6.4 +/- 1.71, 6.06 +/- 1.7 micrograms/ml: Ktz+Ver 11.13 +/- 2.13, 11.63 +/- 2.22, 10.6 +/- 2.1 micrograms/ml: Ktz+Nif 7.37 +/- 1.6, 7.7 +/- 1.57, 7.4 +/- 1.75 micrograms/ml: Ktz+Nim 10.1 +/- 2.28, 10.6 +/- 2.31, 9.91 +/- 2.21 micrograms/ml. These results were significantly different (p < 0.001) compared with ketoconazole. Our findings indicate that some calcium channel antagonists increase the antifungal activity of Ktz against C. albicans in vitro. PMID- 8369014 TI - Permeation mechanisms through artificial lipoidal membranes and effects of synthetic surfactants on xenobiotic permeability. AB - Through the use of permeation/lipophilicity correlations, the mechanisms of permeation of selected test compounds across artificial lipoidal membranes of the polysiloxane type, in the absence and in the presence of a nonionic surfactant (Polysorbate 80), are investigated, in order to design "in vitro" conditions and features suitable for reproducing "in vivo" intestinal absorption tests, as well as to validate some conclusions arising from "in situ" rat gut experiments about the effects of the synthetic surfactants on drug and xenobiotic absorption processes. Six 4-alkylanilines showing a perfect homology were used as test compounds. The reported results clearly show that the in situ biophysical absorption (diffusion) models are completely reproduced by in vitro tests, provided that perfect sink conditions are achieved. Further selection of artificial membrane polarity should be necessary, however, in order to exactly equalize in vitro and in situ permeation rates. As far as the synthetic surfactant action on permeability is concerned, our conclusions are similar to those drawn from in situ studies, except that the effect of the surfactant on membrane polarity is much smaller and the micelle-solubilizing effect somewhat larger. The disruption of the aqueous stagnant diffusion layers adjacent to the membranes by the surfactant has been conclusively demonstrated. A clear first element deviation for aniline, which prevents its inclusion as a term of the tested series, has been observed; this feature should be borne in mind whenever any in vivo/in vitro correlation has to be established. PMID- 8369015 TI - [The effect of mistletoe lectins on the limulus amebocyte lysate test]. AB - Former reports about too high and from batch to batch changing endotoxin contents in mistletoe preparations and phytopharmaceuticals for parenteral administration correlated with clinically observed side effects led to investigations of the endotoxin content of ABNOBA-viscum. For that purpose the endotoxin levels of the raw materials, the equipment and the production steps were observed by using the limulus amebocyte lysate (LAL) test. The mean value found in the preparation containing the highest available concentration (dilution level 2 containing 15 mg of plant extract from 20 mg of fresh mistletoe in 1 ml) came to 66.7 endotoxin units (EU) per ml, corresponding to about one fifth of the commonly accepted limit value of 350 EU/ml, the human pyrogenic dose. Depending on their dilution level, lower concentrated preparations led also to lower LAL test results. It could be proved that lectins contained in mistletoe preparations cause false positive LAL tests. Such results implicate false too high contents of endotoxin. Different lysates, i.e. Limusate, Pyrogel, Pyrogent, and Pyroquant showed approximately the same results. Microbiological and LAL test results indicate that only 10% of the total amount of the LAL test result was caused by endotoxins. So it is necessary to form a new estimation of the former results of determination of the endotoxin content of mistletoe preparations. PMID- 8369017 TI - Patient mix and utilization of resources. PMID- 8369016 TI - Effects of macrophage colony-stimulating factor on the proliferation and the function of Kupffer cells. AB - Using flow cytometric methods, the influence of recombinant human macrophage colony-stimulating factor (rhM-CSF) on DNA synthesis, the phagocytosis of microspheres and the uptake of lipopolysaccharide (LPS) in cultured rat Kupffer cells was investigated. Incubation with 10(3) U/ml of rhM-CSF did not increase the S-phase population of Kupffer cells, however, 10(5) U/ml of M-CSF significantly increased that population from 6.26 +/- 0.68% to 8.31 +/- 0.99%. Significantly increased rate of cells phagocytosing microspheres was provoked by rhM-CSF at concentration higher than 10(3) U/ml. Uptake indexes at concentrations of 10(3), 10(4), 10(5), and 10(6) U/ml of rhM-CSF were 114.2 +/- 7.7, 116.5 +/- 8.7, 117.5 +/- 9.1, and 120.0 +/- 11.5, respectively. Significantly increased rate of cells stained with fluorescent LPS was provoked by rhM-CSF at concentrations higher than 10(5) U/ml. Uptake indexes at concentrations of 10(5) and 10(6) U/ml were 115.2 +/- 6.4 and 118.0 +/- 4.3, respectively. These results indicate that M-CSF has a potency to stimulate DNA synthesis, phagocytic activity, and LPS uptake of mature Kupffer cells in vitro. This potency may be helpful to the enhancement or the recovery of the role of Kupffer cells, which is a part of the host defense mechanism, in diseased states. PMID- 8369018 TI - Autologous pericardial flap for prevention of reentry injury in cardiac reoperations. AB - Cardiac injury during sternal reentry to the heart is a rare but dangerous complication of cardiac reoperations. Positioning a pericardial flap between the heart and sternum at the time of the initial operation may consistently facilitate cardiac reoperation by providing a reliable plane of dissection and by reducing adhesion formation. PMID- 8369019 TI - Diagnosis of pathogenic Entamoeba histolytica infection using a stool ELISA based on monoclonal antibodies to the galactose-specific adhesin. AB - Monoclonal antibodies (MAbs) directed against pathogen-specific epitopes of the galactose adhesin of Entamoeba histolytica were used in an ELISA to detect antigen from pathogenic E. histolytica. Single stool specimens from 74 patients in Bangladesh were used. The ELISA for pathogenic E. histolytica was positive in all 12 stool specimens with pathogenic amebae subsequently cultured, in no stool specimens with nonpathogenic E. histolytica and in 2 of 40 stools with other or no intestinal parasites detected. Specificity and sensitivity of the assay for pathogenic E. histolytica were 97% and 100%, respectively. These preliminary data offer promise for an ELISA using MAbs to the galactose adhesin as a rapid and sensitive means to detect the presence of pathogenic E. histolytica infection in stool specimens. PMID- 8369020 TI - Limits of technology. PMID- 8369021 TI - Transverse carpal ligament reconstruction for carpal tunnel syndrome. PMID- 8369022 TI - Dental enamel growth. PMID- 8369023 TI - The supply of rural physicians. PMID- 8369024 TI - The supply of rural physicians. PMID- 8369025 TI - Re: 'The role of nursing research committees'. PMID- 8369026 TI - Renal function during infrarenal aortic surgery. PMID- 8369027 TI - What do electrocardiographic and echocardiographic changes during cesarean delivery mean? PMID- 8369028 TI - Searching for inaccuracy in clinical laboratory testing using Medicare data. Evidence for prothrombin time. AB - OBJECTIVE: To determine if the occurrence of health outcomes following clinical laboratory testing can be used to identify types of laboratories that may be having higher than expected error rates. DESIGN: Retrospective analysis of Medicare Part B outpatient claims, Part A hospitalization bills, and death records using a case-control study. SETTING: Medicare records from six carrier territories were sampled during the period 1985 through 1987. PATIENTS: A total of 14,755 Medicare patients receiving a prothrombin time test in either a physician office laboratory or a commercial laboratory. OUTCOME MEASURES: Occurrence of a hospitalization for stroke or acute myocardial infarction, death, or no adverse outcome within 6 days of a prothrombin time. RESULTS: In physician office laboratories where prothrombin time test volume is below 40 per month, the odds that a tested patient will experience a stroke or an acute myocardial infarction are up to 1.96 and 3.43 times greater, respectively, than for a similar patient tested in a commercial laboratory. Switching from one laboratory to another between successive prothrombin time tests increased the odds of a stroke or an acute myocardial infarction by 1.57 and 1.32, respectively. Patients in two states with strong laboratory regulatory programs had fewer adverse outcomes. CONCLUSION: Examining patient outcomes subsequent to clinical laboratory testing may be a useful tool for clinical laboratory quality assurance. PMID- 8369029 TI - Magnetic resonance imaging (2) PMID- 8369030 TI - Stretcher's scrotum. PMID- 8369031 TI - Caesarean section for the pre-eclamptic. PMID- 8369032 TI - Pesticides and food. PMID- 8369034 TI - The cardiac risks of noncardiac surgery. PMID- 8369033 TI - Hypoxaemia in young Kenyan children with acute lower respiratory infection. AB - OBJECTIVES: To determine the prevalence, clinical correlates, and outcome of hypoxaemia in acutely ill children with respiratory symptoms. DESIGN: Prospective observational study. SETTING: Paediatric casualty ward of a referral hospital at 1670 m altitude in Nairobi, Kenya. SUBJECTS: 256 Infants and children under 3 years of age with symptoms of respiratory infection. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia, defined as arterial oxygen saturation < 90% determined by pulse oximetry, and condition of patient on the fifth day after admission. RESULTS: Over half (151) of the children were hypoxaemic, and short term mortality was 4.3 times greater in these children. In contrast, the relative risk of a fatal outcome in children with radiographic pneumonia was only 1.03 times that of children without radiographic pneumonia. A logistic regression model showed that in 3-11 month old infants a respiratory rate > or = 70/min, grunting, and retractions were the best independent clinical signs for the prediction of hypoxaemia. In the older children a respiratory rate of > or = 60/min was the single best clinical predictor of hypoxaemia. The presence of hypoxaemia predicted radiographic pneumonia with a sensitivity of 71% and specificity of 55%. CONCLUSIONS: Over half the children presenting to this referral hospital with respiratory symptoms were hypoxaemic. A group of specific clinical signs seem useful in predicting hypoxaemia. The clear association of hypoxaemia with mortality suggests that the detection and effective treatment of hypoxaemia are important aspects of the clinical management of acute infections of the lower respiratory tract in children in hospital in developing regions. PMID- 8369035 TI - Central nervous system toxoplasmosis in AIDS. PMID- 8369036 TI - Dropped head syndrome. PMID- 8369037 TI - Air reduction of an intussusception caused by a pathologic leadpoint in an infant. PMID- 8369038 TI - Cost-effective treatment of Candida esophagitis. PMID- 8369039 TI - Primary structure of the elongation factor 1 alpha in Sulfolobus solfataricus. PMID- 8369040 TI - Chelation treatment of neurological Wilson's disease. AB - The results of chelation treatment of 137 patients presenting with neurological Wilson's disease are described, together with the more commonly observed toxic reactions to the various drugs employed. Fifty-seven patients made an excellent response to treatment and became symptom free. Thirty-six patients made a good recovery, but were left with some minor neurological deficit. Twenty-four patients had a poor response: although the disease process was arrested they were left more or less disabled. Twenty patients died: nine had little or no treatment, but 11 died despite apparently adequate chelation therapy. There was no obvious reason for this failure. The liver copper level was estimated in six of these patients: it was still significantly elevated in only one, but in all four in whom it was possible to make the determination, the concentration of copper in the basal ganglia was in excess of 45 micrograms/g wet weight. It was not apparent why adequate therapy failed to remove copper from the brains of these patients. There was no obvious clinical, histological or biochemical indicator of failure to respond to treatment. Initial deterioration before improvement was seen in 30 patients: the prognosis for a useful recovery was not necessarily worse than that in patients who did not show this phenomenon. PMID- 8369041 TI - Six authors in search of a citation: villains or victims of the Vancouver convention? AB - OBJECTIVES: To analyse trends in the number of authors per article over the past 10 years. DESIGN: Analysis of articles from random volumes of eight biomedical journals. SUBJECTS: Cell, Nature, Proceedings of the National Academy of Sciences USA (PNAS), Journal of Clinical Investigation (JCI), Biochemical and Biophysical Research Communications (BBRC), Journal of Clinical Oncology (JCO), New England Journal of Medicine (NEJM), Lancet. MAIN OUTCOME MEASURES: Median and modal numbers of authors. RESULTS: All journals except Cell and Nature showed a trend towards increasing authorship numbers over the study period. The trend was most noticeable in journals such as JCO which feature clinical research. General medical journals (Lancet, NEJM) with a median of six to seven authors per article published far fewer seven author than six author studies, which suggests that author number may be influenced by the Vancouver convention which precludes citation of more than six authors. CONCLUSIONS: The phenomenon of expanding authorship in biomedical journal articles is not explained by the hypothesis that newer research technologies have necessitated more extensive collaboration. Rather, the data suggest that conferral of authorship may sometimes have a volitional component which contributes to rising author numbers. It is proposed that replacement of the Vancouver convention with a "first author, last author" citation system may help stem this rise in author numbers. PMID- 8369042 TI - Screening for ovarian cancer. PMID- 8369043 TI - Positional asphyxia during law enforcement transport. PMID- 8369044 TI - [Dementia in the elderly. Will we think in AIDS]. PMID- 8369045 TI - Is it necessary to perform appendicectomy in the middle of the night in children? PMID- 8369046 TI - Mycobacteria and sarcoidosis. Mycobacterium tuberculosis an unlikely culprit. PMID- 8369047 TI - Power and gender. PMID- 8369048 TI - Choosing an index for abdominal obesity: an opportunity for epidemiologic clarification. AB - Despite numerous reports that abdominal obesity is related to disease risk, the study of body-fat distribution remains a largely empirical science. Elucidation of the pathophysiologic linkage between abdominal obesity and disease would be better served by generating hypotheses and testing them--the process of deductive science. Physiologists have proposed that adipose tissue of the intra-abdominal compartment (that drained by the portal vein) contributes strongly to atherosclerosis. If this is so, then the volume of the intra-abdominal fat depot might be better correlated with disease states than a less specific anthropometric index such as the waist-to-hip girth ratio. Alternative abdominal obesity indices (e.g. sagittal abdominal diameter divided by thigh girth) could be tested in epidemiologic studies to improve our pathophysiologic understanding of how body-fat distribution is related to atherosclerosis and other diseases. PMID- 8369049 TI - Gauging the accuracy of laboratory testing from Medicare data. PMID- 8369050 TI - Vitiligo, autoimmune disease and melanoma. PMID- 8369051 TI - Cyanocobalamin--a case for withdrawal. PMID- 8369052 TI - Diagnosis of cough variant asthma. PMID- 8369053 TI - Carbamazepine for paroxysmal dystonia due to spinal cord lesions. PMID- 8369054 TI - Directly observed treatment of tuberculosis. PMID- 8369055 TI - Superfund and public health policies: an ATSDR response. PMID- 8369056 TI - The need for asylum. PMID- 8369057 TI - Systematic serologic screening for toxoplasmosis in pregnancy. PMID- 8369058 TI - Long term care of elderly people. Different balance of provision in Scotland. PMID- 8369059 TI - Dural puncture. Elective forceps delivery not indicated. PMID- 8369060 TI - Asthma guidelines. Guidelines ignore psychology of asthma. PMID- 8369061 TI - Urinary incontinence. Social and financial costs high. PMID- 8369062 TI - Epirubicin and the risk of leukemia: not substantiated? International Collaborative Cancer Group Steering Committee. PMID- 8369063 TI - Percutaneous ultrasound guided uterine needle biopsy. PMID- 8369064 TI - Reforming health care. PMID- 8369065 TI - Effect of dietary advice on cholesterol levels. PMID- 8369066 TI - Screening for ovarian cancer. Other chronic diseases affect serum marker. PMID- 8369067 TI - Limiting the drugs list. The trouble with generic prescribing. PMID- 8369068 TI - Skin self-examination. PMID- 8369069 TI - Canadian National Breast Screening Study. PMID- 8369070 TI - Blood lead levels in children. PMID- 8369071 TI - Pulmonary manifestations of multidrug-resistant typhoid fever. PMID- 8369072 TI - Asthma prevention. PMID- 8369073 TI - Cardiac uptake of MIBG in patients with aortic stenosis. PMID- 8369074 TI - Magnetic resonance imaging. PMID- 8369075 TI - IL-2 and MS. PMID- 8369076 TI - Re: "TLVs for asbestos". PMID- 8369077 TI - Exhibitionism treated with clomipramine. PMID- 8369078 TI - Cross-cultural psychiatry and children with deviant behaviors. PMID- 8369079 TI - Warm heart operation for acute ischemia. PMID- 8369080 TI - Normothermic cardiopulmonary bypass. PMID- 8369081 TI - The management of malaria in a district hospital: what drugs? PMID- 8369082 TI - [Autocrine growth mechanisms of cholesteatoma epithelium]. AB - Transforming growth factor alpha (TGF alpha) and interleukin 1 alpha (IL-1 alpha) are known to be produced by normal human keratinocytes stimulating their proliferation. The distribution and expression of TGF alpha and IL-1 alpha were examined in specimens of middle ear cholesteatoma by means of immunohistochemical methods using a monoclonal antibody against TGF alpha and a polyclonal one against IL-1 alpha. Normal retroauricular skin was stained for comparison. Staining for TGF alpha was consistently stronger in cholesteatoma epithelium than in normal epidermis, and encompassed all epithelial cell layers. Immune cells occurring in the stroma of cholesteatoma also reacted positively for TGF alpha. The intensity of staining for IL-1 alpha was markedly stronger in cholesteatoma tissue than in normal epidermis. All cellular layers of the squamous epithelium of cholesteatoma stained strongly and uniformly for IL-1 alpha, whereas the keratin layer was negative for IL-1 alpha. In the connective tissue beneath the cholesteatoma epithelium intensely positive cells were scattered between negative stromal cells. These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF alpha and IL-1 alpha as well as with a paracrine stimulation by immune cells. Both factors contribute to the unrestrained growth of cholesteatoma in the middle ear cavity. PMID- 8369083 TI - [Expression of 4F2-activation antigen in middle ear cholesteatoma]. AB - Cholesteatoma consists of a keratinising squamous epithelium in the middle ear cavity. The human 4F2 antigen appears at the end of the phase G0 and at the beginning of the phase G1, remaining detectable throughout mitosis. This antigen is therefore considered to be an activation marker. In this study the presence and distribution of 4F2 in the cholesteatoma epithelium was investigated using monoclonal antibodies and the alkaline-phosphatase-anti-alkaline-phosphatase method. Normal skin showed positive immunostaining exclusively in the basal keratinocytes. In contrast, all cholesteatomas showed a suprabasal expression of the 4F2 antigen. The results confirm the hyperproliferative character of cholesteatoma epithelium. PMID- 8369084 TI - [Clinical aspects and histopathology of middle ear tuberculosis]. AB - During the past few decades the clinical features of middle ear tuberculosis have changed. Hence, clinical differentiation between tuberculous and non-specific proliferative otitis media and mastoiditis is now difficult. Between 1986 and 1992 five cases of tuberculous otitis media were treated surgically in the ENT Dept. of the University of Hamburg, representing 0.2% of all performed middle ear operations. According to our experience the therapy of choice is the open mastoid cavity with subsequent chemotherapy to avoid recurrent infections. The advantages of this procedure are proven by actual histopathological findings as well as by the analysis of historical microsections of the Wittmaack temporal bone collection: according to these findings, two different types of histopathological alterations can be differentiated. PMID- 8369085 TI - [Effect of adaptation and compensation mechanisms on postoperative function of patients with tumors of the oral cavity]. AB - To examine adaptation and compensation mechanisms on oral function, the tongue and the floor of the mouth of five healthy volunteers were immobilised with a plastic plate. The functional results of this group were compared with the postoperative results of patients with tumours in the area of the anterior floor of the mouth and the edge of the tongue. Swallowing, sucking, and speech functions were used to assess oral function. Unhandicaped swallow and sucking functions were determined as average value (reference value 100%) in a control group with 20 healthy adults. The results of the study demonstrate the adaptive ability of the tongue and underline the importance of keeping the remaining structures free to move. In cases of resection in the area of the anterior floor of the mouth, however, careful soft tissue reconstruction plays a far greater role, since the remaining structures do not adapt as easily. PMID- 8369086 TI - [Importance of increased interstitial fluid pressure in therapy of malignant tumors of the head-neck area]. AB - Animal experiments showed that elevated interstitial fluid pressure (IFP) is associated with poor blood supply and inadequate supply of drugs to solid tumours. IFP is approximately 0 mmHg in most normal tissues. Up to now there have been only few studies showing elevated interstitial pressure in human tumours in situ: Mammary carcinomas, cervical carcinomas and colorectal cancers have an elevated IFP. We measured IFP in squamous cell carcinomas of the head and neck region in humans using the "wick-in-needle" technique. In all lesions (n = 25), the IFP was elevated (4-39 mmHg). The IFP increased with tumour size. The highest IFP was 39 mmHg in a 26 ml tumour. These results show that squamous cell carcinomas of the head and neck region in humans have an elevated interstitial fluid pressure. The elevation of IFP associated with inadequate delivery of drugs to the interstitium of malign tumours may reduce the response to therapy. PMID- 8369088 TI - [Langerhans cell histiocytosis of the tonsil]. AB - Langerhans cell histiocytosis (histiocytosis X) of the tonsil is a rare disorder of histiocytic proliferation with a broad spectrum of clinical symptoms. We report on a case of a solitary histiocytosis of a unilateral tonsillar palatine. To exclude a mesenchymal tumour a 32-year old male with a hyperplasia of the left tonsil underwent surgery. The histopathological examination revealed a solitary infiltration of Langerhans cells. We found a morphologically remarkable intraepithelial hyperplasia of Langerhans cells (S-100 protein positive) on contrast to the opposite side. The CT scans of the neck, thorax, abdomen and pelvis and the bone marrow puncture could not detect any further manifestation of the disease. Therefore, we refrained from systemic therapy. Up to now the patient is without any relapse of the disease for a period of 16 months. PMID- 8369087 TI - [Leiomyosarcoma of the tongue]. AB - We report on a 48-year old female patient presenting with a spherical firm tumour that developed within a period of about three weeks. No causative trauma could be assessed. The tumour was surgically removed and turned out to be a leiomyosarcoma of the tongue. Probably the tumour originated from the vascular smooth muscle cells. Clinically this very rare tumour of the tongue must be differentiated from various benign and malignant mesenchymal neoplasms. Therapeutic considerations and differential diagnosis are discussed in reviewing the literature. PMID- 8369089 TI - [Oropharyngeal anthrax]. AB - We report on a 46-year old man suffering from the oropharyngeal form of human anthrax. The patient presented with a sore throat and extensive swelling of the right neck, the oropharynx and especially the right tonsil. The skin of the mandibular and submandibular region showed vesicular lesions followed by ulcerations resulting in a blackish eschar. The diagnosis was verified by bacteriological culture. Thus, in cases of known exposure, in areas where anthrax is endemic or in immigrant workers coming from such areas, infection with bacillus anthracis should be included in the differential diagnosis of inflammatory oedematous lesions of the oropharynx. PMID- 8369090 TI - [Plasmacytoma of the nose and paranasal sinuses with intracranial and orbital extension]. AB - A rare case of a solitary extramedullary plasmocytoma of the nasal cavity and the paranasal sinuses with orbital and intracranial extension of a 61-year old male patient was examined clinically, histologically and immunohistologically. The interrelationship of the generalised disease (multiple myeloma = MM) and the solitary extramedullary form (extramedullary plasmocytoma = EMP) is discussed as well as the importance of the magnetic resonance imaging in the diagnosis of tumours of the facial part of the skull. PMID- 8369091 TI - [Chronic lipogranuloma (paraffin granuloma) of the eyelids and orbits after endonasal paranasal sinus operation]. AB - During the last five years 10 patients received surgical treatment in our eye clinic for tumours of the eyelids and the orbit that had developed after endonasal sinus surgery. In most patients the first signs of lid or orbital involvement had occurred 4 weeks after ENT surgery and after a unilateral or bilateral postoperative haematoma had subsided. The histological examination of the surgical specimens showed chronic sclerosing lipogranuloma containing large vacuoles surrounded by epithelioid and giant cells, typical of a so-called paraffin granuloma. MR-spectroscopy detected high concentrations of paraffin in the specimens of 3 patients. Since paraffin is a constituent of many ointments, we assume that the granulomatous reaction was elicited by the ointment tampons routinely applied to the wound area following sinus surgery. The bleeding acted as a vehicle to distribute the paraffin into the surrounding tissues. PMID- 8369092 TI - [Spiral CT: differential diagnosis of cervical swelling. Initial clinical results]. AB - Spiral CT examinations were performed pretherapeutically in 27 patients in whom cervical lymph node enlargement had been suspected. The M/Q quotient known from sonography and MR can also be employed in CT by means of coronary and sagittal reconstruction. This improves CT differentiation between reactively changed and metastatically infiltrated lymph nodes in tumour patients. Hence, CT diagnosis can now make use of a highly sensitive and highly specific criterion for diagnosing lymph nodes. Another diagnostic improvement is that vascular infiltrations by lymph node metastases can now be visualised or excluded more readily. Spiral CT is also suitable in tumorous and non-tumorous processes for an accurate assessment of the extension of e.g. retropharyngeal abscesses or laryngoceles. PMID- 8369093 TI - [Suture of tympanic membrane transplants in tympanoplasty to the ventral wall of the auditory canal]. PMID- 8369095 TI - A general method to calculate dose to spine in opposing anterior posterior treatment setup without CT. AB - The spinal cord is usually part of the treatment volume in the treatment of the thorax and abdomen areas using antero-posterior (AP) and postero-anterior (PA) ports. Thus it is necessary to know the dose the spinal cord would receive. One needs to locate the spine to calculate the dose at that location. In the absence of CT, a set of orthogonal films is taken at simulation to aid in locating the spine. The relative point dose then is calculated using irregular field point dose calculation mode of the treatment planning system. The data needed for the calculation are the x and y coordinates of the spine in the coronal plane, air gap, and depth in tissue. Correct entry of these is thus important to obtain the dose accurately. Planning systems assume that the spine is close to the beam axis. There could be possible mislocation of the spine when this assumption is not valid. This presentation describes a procedure to obtain the needed numbers for a general location without any assumptions. To obtain x and y coordinates the suggestion is made to solve numerically using successive approximation series for the coordinates, the series continued until mutually consistent values are obtained. The other parameters, g and d, are obtained from the source to skin distance (SSD) above the spine point, with the use of multiple transaxial contours in association with the principle of linear interpolation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369094 TI - Derivation of angular separation to obtain beam edge coincidence in tangential fields. AB - The separation of the two gantry angles in a pair of tangential fields required to obtain posterior beam edge coincidence is derived. This derivation enables one to calculate the second gantry angle at the time of simulation. Experience has shown that the setup angle is within 1 degree of the calculated value. PMID- 8369096 TI - Target to skin distance determination of oblique beams through a solid simulation table. AB - Oblique beams are commonly used to treat target volumes after cord tolerance is reached. At this institution we rely on the use of the Beams Eye View software to shape boost fields at oblique angles. Before the boost fields begin the patient is taken into the simulator room and set up according to the computerized plan. An integral part in the checking of the boost fields is the verification of the target to skin distances (TSD). Since many simulator couches have a solid top, the posterior oblique TSD cannot be read. With the use of simple geometrical relationships we have found an easy method to check the TSD's, thus aiding in the verification of the computer plan. PMID- 8369097 TI - A new gel using super absorbent polymer for mapping the spatial dose distributions of electron beams by MR imager. AB - A technique for mapping the spatial dose distribution with a magnetic resonance imager is presented. A ferrous sulphate solution with sulfuric acid was used as the detecting medium for radiation dose. To make a gel of the solution for filling up a cubic phantom, we developed a new gel component that is combined with a super absorbent polymer (Sumikagel N-100) and a cross-linked dextran gel (Sephadex G-200). In order to make the application for radiation treatment planning, mapping of the dose distribution was carried out using a Unix computer. PMID- 8369098 TI - An arms-up positioning device for treatment of malignancies of the intrathoracic region. PMID- 8369099 TI - High affinity hippocampal [3H]-glibenclamide binding sites are preserved in Alzheimer's disease. AB - ATP-sensitive K+ channels were examined in sections of the hippocampus from patients with Alzheimer's disease and age-matched control subjects by means of quantitative autoradiography. ATP-sensitive K+ channels were labelled with the sulfonylurea, [3H]-glibenclamide, which is a potent blocker of these channels. The density of cells in the subiculum and the activity of choline acetyltransferase were determined in the same hippocampal tissue samples. In the hippocampal formation of control subjects, the density of high affinity [3H] glibenclamide binding sites ranged from 17.6 +/- 0.9 pmoles/g in the presubiculum to 11.6 +/- 0.6 pmoles/g in the parvo-pyramidal layer of the presubiculum. There was no difference between Alzheimer patients and controls in the level of high affinity [3H]-glibenclamide binding in any hippocampal region although there was a marked loss of subicular cells (reduced by 29% compared to controls) and a reduction in choline acetyltransferase activity (reduced by 60% compared to controls). The results suggest that ATP-sensitive K+ channels are associated with elements in the hippocampus which are preserved in Alzheimer's disease. PMID- 8369100 TI - Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease. AB - A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Brane-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4 dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4 dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline. PMID- 8369101 TI - The effect of age on concentrations of monoamines, amino acids, and their related substances in the cerebrospinal fluid. AB - We studied age-related changes in the concentrations of monoamines, amino acids, and their related substances in the cerebrospinal fluid on 144 neurologically normal subjects. The concentrations of tyrosine, 3-O-methyldopa, dopamine (total), norepinephrine (total), homovanillic acid, p-hydroxyphenylacetic acid, and 5-hydroxytryptophan increased significantly with age (p < 0.05), and the concentration of 3.4-dihydroxyphenylacetic acid displayed a non-significant trend to decrease, whereas concentrations of other monoamine precursors and metabolites were unchanged. We found the significant positive correlations between the concentrations of HVA and 5-HIAA (p < 0.001), between tyrosine and tryptophan (p < 0.001), and between tyrosine and 3-O-methyldopa (p < 0.001). The concentrations of asparagine, glycine, taurine, and alanine increased significantly with age (p < 0.05), while glutamine, arginine, and threonine concentrations did not change with age. The aspartate, glutamate, and GABA concentrations displayed the non significant trends to decrease in the elderly subjects. The concentrations of aspartate, glutamate, and GABA had mutually significant positive correlations (p < 0.05), but had significant negative correlations with the concentrations of some neutral amino acids. The urate and xanthine concentrations increased significantly with age (p < 0.01). These findings suggest that the concentrations of monoamine and amino acid transmitters and their related compounds in the cerebrospinal fluid reflect age-related changes in the synthesis, release, and reuptake mechanisms of the transmitters and their transport mechanisms across the blood-brain barrier. PMID- 8369102 TI - Circadian secretion pattern of melatonin in de novo parkinsonian patients: evidence for phase-shifting properties of l-dopa. AB - Aim of this study was the characterization of the circadian melatonin profile in de novo Parkinson patients (N = 9, age 60.0 +/- 3.2 years, mean +/- SEM) and the comparison of these profiles with those of controls and Parkinson patients treated with l-dopa/decarboxylase inhibitor (l-dopa/DCI). We collected 14 venous blood samples during a period of 24 hours and measured the serum melatonin levels by a radioimmuno assay. De novo Parkinson patients displayed the nocturnal melatonin peak (acrophase) at the same time as controls and significantly later than l-dopa/DCI treated patients (1:54 +/- 15.6 min [average clock time +/- SEM in minutes] vs. 1:45 +/- 15.6 min vs. 0:13 +/- 40.8 min). The amount of secreted melatonin did not differ among the three groups. Stage and duration of Parkinson's disease did not correlate with the amount of secreted melatonin. Patients of the tremor subgroup, however, secreted more melatonin than patients presenting only with rigidity and akinesia. The phase advance in Parkinson patients treated with l-dopa/DCI is possibly due to a central nervous dopaminergic effect elicited by l-dopa administration and not inherent to Parkinson's disease per se. PMID- 8369103 TI - Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease. AB - The objective of this questionnaire-based survey was to evaluate the prevalence and causes of sleep disturbances in 90 nondepressive patients with Parkinson's disease (PD) and 71 age-matched healthy subjects. We also assessed the prevalence and characteristics of excessive daytime sleepiness (both groups) and excessive fatigue (PD patients). A high prevalence of sleep disturbances in PD patients was found; this is to a large extent probably the result of aging. As compared with controls, patients had a more severely disturbed sleep maintenance because of nycturia, pain, stiffness, and problems with turning in bed. The prevalence of excessive dreaming is similar in both groups, but altered dream experiences almost exclusively occurred in PD. Patients rated themselves more often to be morning-types than controls. This finding may account for the reported adaptation effects in experimental settings and the reduced REM latency in PD patients. The prevalence of daytime sleepiness was similar in both groups. Excessive daytime sleepiness showed a clear diurnal pattern with a peak in the early afternoon. As for excessive fatigue, the majority of the patients did not report a preferential time for this symptom. Our findings further argue against an association of fatigue with any circadian factor, and instead suggest a relationship with the motor deficits of PD. PMID- 8369104 TI - Alteration of protein kinase C activity in the postischemic rat brain areas using in vitro [3H]phorbol 12,13-dibutyrate autoradiography. AB - Chronological changes of protein kinase C (PKC) activity were measured using in vitro [3H]phorbol 12,13-dibutyrate (PDBu) autoradiography to investigate the postischemic alteration of this second messenger system in the rat brain. Transient ischemia was induced by the occlusion of the middle cerebral artery (MCA) for 90 min and such occlusion followed by various recirculation periods of up to 4 weeks. After 90 min of ischemia followed by 3 hours of recirculation, [3H]PDBu binding sites were found to be significantly decreased in the cerebral cortex and lateral segment of the caudate putamen, both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischemic foci. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, a significant decrease of [3H]PDBu binding sites was first detected in the ipsilateral thalamus and the substantia nigra, which both areas had not been directly affected by the original ischemic insult. This postischemic delayed phenomenon observed in the thalamus and the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. These results suggest that alteration of second messenger (PKC) pathways may be involved not only in the ischemic foci, but also in neuronal degeneration of the exo-focal remote areas in relation to the disruption of intracellular calcium homeostasis which plays a key role in the pathogenesis of postischemic neuronal damage and that marked alteration of intracellular signal transduction may precede the neuronal damage in the exo-focal postischemic brain areas. PMID- 8369105 TI - Circadian variations of superoxide dismutase activity in the rat pineal gland. AB - The 24 h profile of the activity of the antioxidant enzyme superoxide dismutase (SOD) in the pineal gland of rats was studied. Rhythmic analysis showed a significant 24 h rhythm with an amplitude of oscillation of 25% of the 24 h mean value, that was 100.34 +/- 1.6 U SOD (nitrite). An ultradian rhythm of 9 h was also detected. The diurnal profile of superoxide dismutase activity is discussed in relation to the oxidative metabolism of the pineal gland. PMID- 8369106 TI - Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4 tetrahydroisoquinolines and their N-methylated derivatives. AB - 6,7-Dihydroxy-1,2,3,4-tetrahydroisoquinoline (norsalsolinol) and 1-methyl-6,7 dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), and their N-methylated derivatives were found to inhibit type A and B monoamine oxidase isolated from human brain synaptosomal mitochondria. N-Methyl-norsalsolinol, (R) and (S) enantiomer of salsolinol, and N-methyl-salsolinols inhibited type A monoamine oxidase competitively to the substrate, kynuramine, and R enantiomers were more potent inhibitors than S enantiomers. The inhibition was reversible. Norsalsolinol induced positive cooperativity toward kynuramine. Both norsalsolinol and N-methyl-norsalsolinol inhibited type B oxidase non competitively to the substrate, and their Ki values were much higher than those to type A. Types of inhibition of type A monoamine oxidase depended on the enzyme sources. Inhibition of monoamine oxidase by 6,7-dihydroxy-1,2,3,4 tetrahydroisoquinolines is discussed in relation to their chemical structures. PMID- 8369107 TI - Modulation of serotonin binding sites in the brain of the Djungarian hamster, Phodopus sungorus, during adaptation to a short photoperiod. AB - During the physiological adaptation of the Djungarian hamster, Phodopus sungorus, to a short photoperiod in autumn the modulation of specific serotonin (5-HT) binding sites of synaptic membranes was investigated in two brain regions, i.e. cerebral cortex and basal brain (CNS without cerebral cortex, cerebellum, pineal gland, and spinal cord). The radioligands [3H]5-HT and [3H]ketanserin were used to characterize total 5-HT1 and 5-HT2 binding sites, respectively. An increase of 5-HT1 and 5-HT2 binding sites was observed in both brain regions within 14 days after reduction of the photoperiod from a 14:10 h light/dark (l/d) cycle to an 8:16 h l/d cycle. The increase was still present after 56 days of the short photoperiod. Binding kinetics assayed after 4 days of the short photoperiod show that maximal specific binding of [3H]5-HT and [3H]ketanserin was increased, while dissociation constants (KD) were not changed. The membrane anisotropy of synaptic membranes, measured by fluorescence polarization, was reduced transiently during the early part of the adaptation. Neither the phospholipids nor the mole ratio of cholesterol to phospholipids were significantly affected by adaptation to short photoperiod. The results suggest an important role of the central nervous 5-HT system in the physiological adaptation of the Djungarian hamster to a short photoperiod. PMID- 8369108 TI - Therapy with central active catechol-O-methyltransferase (COMT)-inhibitors: is addition of monoamine oxidase (MAO)-inhibitors necessary to slow progress of neurodegenerative disorders? AB - Neurotrophic factors, like e.g. nerve growth factor (NGF), neurotrophin 3 (NT-3) or brain-derived neurotrophic factor (BDNF) promote the survival and function of neurones in the peripheral and central nervous system. Dopamine or other biogenic amines induce the biosynthesis of neurotrophic factors in glial and neuronal cells. Therefore inhibition of enzymes, like the extraneuronal and neuronal located MAO or the predominantly glial situated COMT, which both metabolize catecholamines, may induce an increased biosynthesis of neurotrophic factors. Due to clinical studies especially MAO-B-inhibitors appear to slow the progression of neurological deficits in Parkinson's disease and the cognitive decline in Alzheimer's disease. On the one hand inhibition of COMT alone may also slow the metabolisation of biogenic amines in glial cells and may consequently induce synthesis of neurotrophic factors in glial cells. But on the other hand in vivo and in vitro studies show, that COMT-inhibitors may intensify the metabolisation of catecholamines in neurones by MAO, what may cause an enhanced generation of free radicals. This increase of free radicals may induce lipid peroxidation of membranes and therefore cause accelerated neuronal and glial cell death. For that reason we conclude, that centrally active COMT-inhibitors may only be used together with MAO-inhibitors in the neuroprotective treatment of neurodegenerative disorders. Medical treatment with both inhibitors will have to be performed very carefully due to cytotoxic effects of high catecholamine levels on neuronal and glial cells and due to possible prolongation or potentiation of the activity of several noradrenergic drugs in the periphery. PMID- 8369109 TI - Vitamin E attenuates the development of haloperidol-induced dopaminergic hypersensitivity in rats: possible implications for tardive dyskinesia. AB - Chronic haloperidol treatment in rats results in behavioural supersensitivity to dopamine agonists. This mechanism has been suggested as a possible animal model for tardive dyskinesia. In the present study the simultaneous administration of vitamin E to chronic haloperidol treatment in rats prevented the development of behavioural supersensitivity to apomorphine. This finding suggest that the concomitant administration of vitamin E to neuroleptics might prevent the development of tardive dyskinesia in humans. PMID- 8369110 TI - U.S. Environmental Protection Agency's Ozone Epidemiology Research Program: a strategy for assessing the effects of ambient ozone exposure upon morbidity in exposed populations. AB - The Clean Air Act Amendments of 1990 mandate a future reduction of ambient ozone levels in many areas of the country, the cost of which will be great. In order to assess the current public health burden of ambient ozone exposure and to provide information for assessment of potential health benefits of improved air quality, the Health Effects Research Laboratory of the U.S. EPA has undertaken an Ozone Epidemiology Research Program. The research strategy which will guide this scientific program is described in this paper. Criteria for selection of important research questions as well as issues which cut across all questions and study designs are discussed. In particular, this program emphasizes the study of effects which reflect morbidity in the population. The three questions identified as being of most immediate importance involve the relationship of short-term ambient ozone exposure to acute respiratory illness, the relationship of recurrent exposure to chronic respiratory disease, and the relationship of recurrent exposure to development of acute respiratory illness. Specific research approaches and initial projects to address these three questions are described. PMID- 8369111 TI - Reducing the risks from radon. AB - The U.S. Environmental Protection Agency estimates that residential radon levels in the United States lead to approximately 13,600 lung cancer deaths per year. To address this problem, the Agency has identified three program initiatives that can provide substantial reductions in the public's risks: (1) public information activities that urge the public to test for radon and reduce elevated concentrations in existing homes, (2) new construction standards to reduce radon entry, and (3) radon testing and mitigation during real estate transactions. This paper analyzes the costs and risk reductions that could result from the implementation of these major initiatives, showing how all three elements cost effectively protect the public's health. PMID- 8369112 TI - Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the Total Human Environmental Exposure Study (THEES). AB - The Total Human Environmental Exposure Study (THEES) was an investigation of multimedia exposure to the ubiquitous environmental carcinogen, benzo(a)pyrene (BaP). The three-phase study was conducted in Phillipsburg, New Jersey and involved the participation of 14-15 individuals (8-10 homes) during each 14-day monitoring period. Microenvironmental sampling of air, food, water and soil indicated that environmental exposure to BaP was primarily through air and food. Exposure and risk estimates were, therefore, based on the results of personal monitoring of breathing zone air and prepared food samples. Based on a comparison of the range and magnitude of inhalation and dietary BaP exposures, food ingestion was clearly the predominant exposure to pathway. The relative contributions of other potential sources of community exposure to BaP (e.g., soil and drinking water ingestion) were also assessed. The excess cancer risk estimates for food ingestion were consistently greater than those for personal air, reflecting both the predominantly higher BaP exposures through the diet and the higher carcinogenic potency value for oral exposure. Overall, the total lifetime risk from personal exposure to BaP for nonsmokers in the community was estimated at 10(-5). In identifying risk reduction options, it is important to account for the observation that personal activities, lifestyle, and diet strongly influenced individual exposures to BaP. PMID- 8369113 TI - Treatment of cholesteatoma and retraction pockets. AB - Treatment of retraction pockets (RP) and cholesteatomas depends on their nature and evolvement and the size of mastoid pneumatization. RP are secondary to vacillating middle ear negative pressure. Treatment when necessary consists of placing a ventilating tube, excision of the RP or both. In most children and adults, cholesteatoma is derived from RP (or "atelectasis") of the tympanic membrane, where it can be termed "retraction pocket" cholesteatoma or "secondary" cholesteatoma. This type of cholesteatoma is associated with a non-pneumatized mastoid coupled by negative pressure. Approximately one-third of children's cholesteatomas present clinically behind an intact drum despite a pneumatized mastoid. Pathogenetically this type may be "congenital" or "metaplastic" and should be best termed "primary" cholesteatoma. Central perforations associated with cholesteatoma are probably derived from continuous tympanic membrane destruction by infection in cases of RP cholesteatomas or due to a primary cholesteatoma bursting out from the tympanic cavity. Canal-up surgery of cholesteatoma fails in 60% of cases at Tel Aviv University because of the inherent tendency of the tympanic membrane to retract once again. Residual disease was found in our cases to be a lesser cause for failure. Treatment depends on the type of cholesteatoma, emphasizing small "radicals" in sclerotic mastoids. When a pneumatized mastoid is encountered, a posterior tympanotomy should be considered. PMID- 8369115 TI - Variations of the ethmoid labyrinth and sphenoid sinus and CT imaging. AB - Three hundred macerated and partly isolated postmortem mid-facial bones were studied for the development, variations and dimensions of the structures of the nasal cavity. On 184 axial CT scans of bones (102 male, 82 female) from patients ranging in age from 1 to 90 years old, the dimensions of the ethmoid labyrinth and sphenoid sinus were studied in detail in order to determine which anatomic situation might be unsafe during clinical endoscopic interventions. Six anatomic variations were identified. Most unsafe for surgery seemed to be the following types: type III, in which the anterior diameter of the ethmoid labyrinth was large and the posterior ethmoid and sphenoid diameters were relatively narrow; type V, in which both ethmoid dimensions were large and the sphenoid diameter was narrow: type VI, in which the ethmoid labyrinth had an "hour-glass" shape. Present findings indicate that CT orientation before any endoscopic intervention might help to avoid serious complications. PMID- 8369116 TI - Specific activities of antioxidative enzymes in the cochlea of guinea pigs at different stages of development. AB - Significant activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were found in the cochleas of guinea pigs of different ages. The specific activities of SOD and GSH-Px (expressed as units/mg protein) increased significantly from fetal animals to animals 2 days old and then to 6-month-old animals. PMID- 8369114 TI - Chemotherapeutic drug resistance in the management of head and neck cancer. AB - Considerable progress has been made in the development of more effective chemotherapy regimens for squamous cell head and neck carcinomas. Unfortunately, increased response rates have not been translated into marked improvements in survival since durations of response have been brief, and the natural history of the disease has ultimately remained unaltered. Since the development of drug resistance is a major obstacle to successful antineoplastic chemotherapy, comprehensive efforts have been focused on understanding the underlying mechanisms. In this review, general and specific aspects of drug resistance related to head and neck cancer are addressed. In particular, mechanisms of resistance towards the most widely used antineoplastic drugs in head and neck malignancies--methotrexate, cisplatin, 5-fluorouracil, bleomycin, and vincristine -are discussed. PMID- 8369117 TI - Arachidonic acid metabolism by isolated and cultured middle ear epithelial cells from the chinchilla. AB - Thin-layer chromatography was used to examine the metabolism of arachidonic acid and prostaglandins (PGs) in freshly isolated and cultured middle ear epithelial cells from the chinchilla. The freshly isolated cells converted arachidonic acid predominantly to PGE2, while those cells grown in culture for 10 days acquired the ability to convert arachidonic acid to 6-keto-PGF1 alpha, PGD2, and PGE2. Incubation of the isolated cells and primary cultures with acetylsalicylic acid and indomethacin inhibited the formation of these PGs. These findings suggest that studies on the factors regulating arachidonic acid metabolism in middle ear epithelium may help to explain the role of eicosanoids in middle ear secretions, particularly in relation to the pathophysiology of otitis media. PMID- 8369118 TI - Influence of LAK cells on expression of HLA-DR antigen on laryngeal carcinoma cell line in new culture systems. AB - We demonstrated the enhancement of HLA-DR antigen expression on cultured laryngeal carcinoma cells (Hep 2) by in vitro cultivation with LAK cells using flow cytometric and immunohistological analysis. For in vitro cultivation of tumor cells with LAK cells, we used newly developed experimental systems (the Transwell double-dish system and experimental three-dimensional tumors). In flow cytometric analysis, expression of HLA-DR antigen on tumor cells was compared before and after co-cultivation with LAK cells. When tumor cells were cultured separately with LAK cells in a Transwell Petri dish and the expression of HLA-DR antigen on tumor cells was analyzed by flow cytometry, the expression of HLA-DR antigen on tumor cells was increased in a dose-dependent manner related to the number of LAK cells used. Furthermore, when anti-interferon-gamma monoclonal antibody was added to the experimental system, enhancement of HLA-DR antigen expression was blocked. These findings were consistent with immunohistological studies, in which experimental three-dimensional Hep 2 cell tumors were established in double-layered agar with/without being co-cultivated with LAK cells. The expression of HLA-DR antigen in this system was significantly increased when compared to such expression before cultivation with LAK cells. These findings suggested that the culture systems employed in this study could be a possible model for examining solid tumor in vivo biological responses. This enhanced expression of HLA-DR antigen may also represent one of the multi factorial responses seen with adoptive LAK cell immunotherapy for solid tumors. PMID- 8369119 TI - Gait analysis in patients with vertigo. AB - Gait analysis utilizing foot switches and electromyography of antigravity muscles was performed on 31 patients with vertigo. Twenty-one cases had peripheral vestibular lesions (such as vestibular neuronitis, Meniere's disease, traumatic labyrinthitis, small acoustic neuroma), and 10 cases had central lesions (such as spinocerebellar degeneration, pontine glioma, cerebellar tumor and giant acoustic neuroma). Parameters employed for analysis included time from heel strike to forefoot strike (HA-I), time from heel off to forefoot off (HA-II) as well as durations of stance, swing and (initial) double supports (DS). Fourteen healthy adults served as controls. The overall incidence of abnormality was highest in HA I, followed by stance and swing. The occurrence of abnormalities in stance, swing and DS was higher in the central lesion when compared with the group having peripheral lesions. The significance and usefulness of gait analysis for dizzy patients are discussed. PMID- 8369120 TI - Mycobacterial species causing cervicofacial infection in Turkey. AB - The aim of the study was to determine the mycobacterial species causing cervical lymphadenitis at Cukurova University Hospital, Adana, Turkey. To this end, culture and differential tests were performed on excisional or incisional biopsy specimens from patients with mycobacterial cervical disease (MCD). The diagnosis was confirmed by skin tests, histopathological examination and positive cultures. In 15 of 40 cases diagnosed as MCD, mycobacteria were isolated in Lowenstein Jensen medium. The etiological agents were tuberculous mycobacteria (Mycobacterium tuberculosis in 9 cases and M. bovis in 3 cases). Of the 3 non tuberculous cases, 2 were due to M. kansasii and the other to M. fortuitum. Antituberculous chemotherapy was given in all cases over an average period of 18 months. A combination of three of four drugs was used including isoniazid, ethambutol, rifampin and/or streptomycin. At the end a follow-up period of at least 3 years, there were no recurrences or persistences of infection and no surgical treatment was necessary to remove residual lymph nodes. PMID- 8369121 TI - Effects of cocaine on human nasal mucosa. AB - The effects of cocaine on the contractile response of isolated human nasal mucosal blood vessels to field stimulation and methoxamine were investigated. Results showed that cocaine antagonized methoxamine and inhibited field stimulation. The drug increased resting tension in human nasal mucosa in vitro through direct actions and potentiated mucosal contractions by norepinephrine and epinephrine. The study indicated that high concentrations of cocaine may actually antagonize alpha-adrenoceptors, but these concentrations are not necessary in eliciting desired degrees of vasoconstriction in nasal blood vessels while being applied as a local anesthetic. PMID- 8369122 TI - A comparison of current expressions of nasal patency. AB - Rhinomanometry is well established as a useful clinical method for objective assessment of nasal patency, although several expressions of nasal patency have been reported and universal standardization has not been achieved. In this communication, nasal resistances were calculated from the equation R = delta P/V (R; resistance; delta P; transnasal differential pressure; V; nasal airflow) at delta P 100 Pa and at peak flow. Time-averaged nasal resistances and integrated nasal patencies were measured in 350 adult patients by Rhinorheograph MPR-1100 and processed by a NI-101 computer program. The values from the equation R = delta P/V at delta P 100 Pa were slightly lower than those from the same equation at peak flow or those from the time-averaging method. Correlations between the values of nasal resistance at peak flow and the time averaging method were very close to the line of identity. No significant correlations were demonstrated between integrated nasal patency and the values from the other three expressions. The differences of the results from these expression are discussed. PMID- 8369123 TI - Melanoma and pregnancy. A review. AB - In the last half-century the incidence of cutaneous malignant melanoma has increased all over the world according to available reports. No association between risk of melanoma and age at menarche, first birth, menopause or duration of reproductive period has been proven so far. Studies on the effect of parity on relative risk and survival have given divergent results with multiparous women possibly having a better prognosis than nullipara. Women with melanoma diagnosed during pregnancy tend to have thicker tumours, shorter disease-free interval and, maybe, lower 10-year survival rate than non-pregnant matched controls. There is no conclusive evidence that therapeutic abortion improves the cure rate. Multivariate analysis has failed to unveil impaired prognosis in women who become pregnant subsequent to diagnosis. PMID- 8369124 TI - Decision analysis--a helpful tool for clinicians to establish diagnostic therapeutic guidelines? AB - In this paper we focus on the question: Does decision analysis provide a framework to assess the value of diagnostic tests in clinical practice and how can it be used by clinicians in establishing diagnostic-therapeutic guidelines. To study this question we performed two analyses concerning the use of pelvic lymphadenectomy and pedal lymphography for staging prostate cancer. Both analyses yielded similar results as far as the preferred strategy was concerned, yet the approach and set up of the two analyses were different. The first analysis was performed in accordance with the textbooks on decision analysis. However, using this traditional approach we encountered some difficulties: in structuring the decision tree, in eliciting values for the quality of life parameters, and in interpreting the results. These difficulties urged us to modify the approach, presented in the second analysis. In this second analysis, the decision problem was split into several consecutive decision problems which corresponded to the questions posed by the clinicians. Longevity and quality of life were considered separately and the consequences of treatment and testing, which affect the quality of life of the patients, were indicated by just two parameters. Finally, the result of the analysis was expressed in clinically meaningful terms. The second analysis is compared with different approaches presented in the literature for analyzing decision problems involving diagnostic tests. Despite some unresolved methodological problems it is concluded that decision analysis provides a good framework for clinicians to structure and analyze complex decision problems. PMID- 8369125 TI - Non-Hodgkin's lymphoma in northern Sweden. A retrospective analysis of morphologic diagnosis and stage in a material from the Swedish Cancer Registry. AB - Morphologic diagnosis and clinical stage were studied in a retrospective material of non-Hodgkin's lymphomas comprising 352 patients diagnosed 1978 until 1982 and reported to a regional cancer registry. Classification was made according to the original Kiel classification. Patients who could be classified as belonging to low- (46%) or high-grade (47%) malignancy groups (n = 337) were further studied. The median age was high, 65 years, which probably reflects the low degree of selection in a regional register material compared to most hospital register based materials. The proportion of stage I cases was rather high, in low-grade lymphomas 24%, and in high-grade 39%, which can be attributed to incomplete staging procedures in old patients. The aim of the study was to illustrate the distribution according to morphologic subclasses and clinical features in a material with a low degree of patient selection. PMID- 8369126 TI - Esthesioneuroblastoma. A report of seven cases. AB - The biologic behavior of esthesioneuroblastoma in seven patients, treated from 1978 to 1989, is reviewed. The patients were initially treated with surgical resection (2 cases), radiation alone (1 case) or a combination of radiation and surgery (4 cases). The radiation dose ranged from 30 to 62 Gy. Operations were performed via a transmaxillary approach (2 cases), lateral rhinotomy approach (3 cases) and craniofacial approach (1 case). Four of the seven patients experienced local recurrence, occurring after disease-free intervals as long as 6 years. The other three patients died of distant metastasis within one year after initial treatment. The effectiveness of radiation therapy varied, and in some patients a dose of 60 Gy was not enough to control microscopic disease. One patient developed bone marrow metastases which was fatal due to the ensuing pancytopenia. One patient developed a brain metastasis. Hyams' histopathologic staging of the tumor appeared to be related to prognosis. PMID- 8369127 TI - Therapeutic use of granulocyte-macrophage colony-stimulating factor (GM-CSF). A review of recent experience. AB - Recombinant cytokines are now available for clinical use. Several colony stimulating factors (CFS) have been identified which induce activation, proliferation and maturation of myeloid lineage cells. Recent therapeutic trials with granulocyte-macrophage colony-stimulating factors (GM-CSF) in association with chemotherapy, bone marrow transplantation and leukemia treatment are reviewed. GM-CSF as primary treatment for myelodysplasia and other types of bone marrow failure is also of interest. Colony-stimulating factor therapy in AIDS may be useful in order to reduce myelodepression caused by antiviral treatment and chemotherapy for associated malignancies like Kaposi's sarcoma. However, the effect of neutrophil count increase on infection is far from clear, and the real benefit of GM-CSF in cancer therapy has yet to be demonstrated. PMID- 8369128 TI - Estimation of creatinine clearance without 24-hour urine collection--a useful guide during cisplatin therapy. AB - The validity of the Cockroft and Gault formula in monitoring renal function during cisplatin therapy was examined in 110 consecutive cancer patients. A good correlation between estimated creatinine clearance (ECC) and the standard measured creatinine clearance (MCC) was found both before and after the onset of cisplatin. The correlation was better in males (r = 0.78 prior to cisplatin and r = 0.79 after the initiation of cisplatin) than in females (r = 0.69 and r = 0.63 respectively). Obesity (> 125% of ideal body weight) had no major effect on the correlation between ECC and MCC. The presence of third-space body fluids, on the other hand, had an influence on the relations between ECC and MCC, particularly in females (r = 0.49). It is concluded that estimation of creatinine clearance, without the cumbersome collection of 24-h urine specimens, is accurate enough for the purpose of adjusting cisplatin dose. It should not be used in females with third-space body fluids. PMID- 8369129 TI - Comparison of ondansetron with customary treatment in the prophylaxis of nausea and emesis induced by non-cisplatin containing chemotherapy. AB - One hundred cancer patients receiving non-cisplatin containing chemotherapy were entered in a prospective study in which the efficacy of ondansetron was compared with standard antiemetic treatments in the prophylaxis of nausea and emesis. During the first 24 h, 77% of patients on ondansetron reported complete control of emesis compared with 56% of those on customary treatments (p = 0.03). However, no statistically significant difference was observed between ondansetron and customary treatments in control of delayed emesis on days 2-5. Nor was any statistically significant difference seen between ondansetron and customary treatments in preventing acute or delayed nausea. PMID- 8369130 TI - Quantification of apoptosis and necrosis by flow cytometry. AB - Apoptosis and necrosis are two important mechanisms of cell death. Several methods have recently been described for quantifying apoptotic cells by flow cytometry. We report a novel method for the quantification and separation of viable normal and apoptotic cells. We have applied this method both to immature rat thymocytes treated with a variety of agents and to a murine haemopoetic cell line after withdrawal of a growth factor. The cells were incubated with two dyes which give fluorescent complexes when bound to DNA, the bis-benzimidazole, Hoechst 33342, and propidium iodide. Three populations were identified and characterized. On excitation with UV radiation, dead cells fluoresced red due to the uptake of propidium iodide whereas apoptotic cells fluoresced bright blue; normal cells showed low blue, low red fluorescence. In this paper, we demonstrate how this method may be used to help to distinguish between cell death by apoptosis and necrosis. PMID- 8369131 TI - A method for dose calculation for high energy photon beams based on measurements performed at reference depth. AB - An algorithm is proposed to calculate the dose per monitor unit at any point along the beam axis for blocked or unblocked fields. The proposed formalism takes into consideration the beam measurements performed at the reference depth as recommended by most dosimetry protocols (5 cm or 10 cm depending on the beam quality). The only parameters which cannot be measured at the reference depth are the peak scatter factors, but they appear only as a ratio of two peak scatter factors for two slightly different field sizes. A correction factor is proposed when the distance of one shielding block to the beam axis is smaller than 5 cm. An agreement better than 1% has been obtained between calculations and measurements in the range of beam qualities, distances to the source and field sizes defined by typical collimators or shielding blocks, usually encountered in clinical practice. PMID- 8369132 TI - In vivo dosimetry with TLD in conservative treatment of breast cancer patients treated with the EORTC protocol 22881. AB - Two anthropomorphic phantom breasts and six patients with breast carcinoma were irradiated according the prescriptions of the EORTC protocol 22881 on the conservative management of breast carcinoma by tumorectomy and radiotherapy. During the implantation procedure for an iridium-192 boost, three tubes were implanted, enabling the measurement with TLD rods of the dose within the breasts of the phantom and the patients during one fraction of the external x-ray therapy and during the interstitial therapy. Measured doses were compared with calculated values from a 2-D dose planning system. In general a fair agreement was found between the measured and calculated doses in points within the breast for the external beam therapy as well as for the interstitial treatment. PMID- 8369133 TI - External beam treatment planning. Can we deliver what we plan? AB - Many sources of uncertainty exist in the delivery of the prescribed dose to the specified target volume in external beam radiotherapy. Their magnitudes are compared with recommendations for the overall accuracy of dose delivery (+/- 5%). Five dose intercomparisons are reviewed, including a recent UK survey undertaken by the Institute of Physical Sciences in Medicine (IPSM). For phantom doses, standard deviations in the ratio of stated to delivered doses range from 1-3.5%, with larger uncertainties when irradiation of volumes within anthropomorphic phantoms is considered. In addition, uncertainties arise from geometrical discrepancies, and the role of portal films in their assessment is also considered. Imaging during radiotherapy will be increasingly important in the development of complex conformal treatments, where the shape of the target volume may be irregular. PMID- 8369134 TI - Target dose versus extratarget dose in stereotactic radiosurgery. AB - In radiosurgery the dose in the periphery of the target is generally about 50-70% of the maximum dose. This type of dose distribution may be expected to be beneficial when tumours containing anoxic, more radioresistant, cells are treated. However, the impact of a high maximum dose in the target on the dose outside the target is of importance for the risk of complications. Dose distributions have been calculated for different beam geometries applicable to radiosurgery by integration of the dose from a continuum of beams. The dose distributions were calculated for beams of different diameters, and the distributions were weighted to give the same dose in the periphery of the target. With a 4 pi beam geometry it is shown that the maximum dose in the central parts of the target can be increased by a factor of 2, by using beams with smaller diameters, at the cost of a marginal increase of the dose outside the target. The average dose in the normal tissue outside increases from 29.8% with 18 mm beams to 34.1% with 14 mm beams, while the average dose within the target increases from 100 to 158%. In radiosurgery of tumours a high maximum dose in the target may give a therapeutic gain. PMID- 8369135 TI - Lymphoma and type I membrano-proliferative glomerulonephritis--a case report. PMID- 8369136 TI - Reconstructive surgery for metastatic destruction of the acetabulum. PMID- 8369137 TI - Temperature-dependent selection in the transmission of mitochondrial DNA in Drosophila. AB - We previously reported a selective mode of mitochondrial DNA (mtDNA) transmission in mtDNA heteroplasmy that was induced artificially in Drosophila melanogaster; the transmission bias appeared to depend on the particular temperature at which heteroplasmic lines were maintained. Here we report investigations of the temperature-dependent mode of mtDNA transmission in heteroplasmic lines for intra and interspecific combinations maintained separately at 22.5 degrees C, 25 degrees C and 29 degrees C for 20 generations. We have examined a selection model for mitochondrial transmission, similar to genetic selection in haploid organisms. Changes in the relative proportions of two types of mtDNA fit the expectations from the model well. The intensity of selection estimated as a selection coefficient depends on temperature. Temperature-sensitive processes thus appear to be involved in the transmission and maintenance of mitochondria. PMID- 8369138 TI - Synthesis of free X duplications carrying a specific region of the centromeric heterochromatin in Drosophila melanogaster. AB - Free X duplication chromosomes of Drosophila melanogaster were synthesized by X ray irradiating the In(1)scL8Lsc8R chromosome which has a deletion in the distal half of hA and the proximal half of hB of the centromeric heterochromatin. Fifty nine duplications have been isolated and cytogenetically analyzed. They all carry wild-type allele of the yellow gene, y+, which should come from the distal tip of In(1)scL8Lsc8R. They appear to be telocentric and predominantly heterochromatic. Majority of the duplications, especially in the classes MEDIUM and LARGE, can pair with XYL.YS in the male meiosis, indicating that they carry male meiotic pairing site(s) that is known to be located exclusively in the X heterochromatin. Complementation test in the males, Df(1)svr, v/Dp, y+, demonstrates that most of the duplications in the classes MEDIUM and LARGE carry euchromatin enough to cover the deletion. The portion of the euchromatin should be of the very proximal region close to the irradiated X chromosome centromere. PMID- 8369139 TI - A theoretical approach to chromosome banding pattern analysis. AB - Based on a schematic model of karyotype evolution, a new methodology for G-, R-, or Q-banding pattern analysis was investigated. Banding pattern analysis essentially depends on the unidirectional alteration and the randomness of the exchange sites of the AM-inversion. In karyotypes that evolved by AM-inversion and Robertsonian rearrangement, two matching patterns appear; (1) tandem and (2) complementary matching patterns. The former is characteristic of a single lineage sharing the same AM-inversions, and the latter appears in different lineages sharing different AM-inversions, by which it is theoretically possible to detect the ancestral karyotype and to reconstruct the karyotype phylogeny (cladogram). In contrast, the evolutionary pathway cannot always be perceived if karyotypes evolve only by Robertsonian rearrangement. The tandem matching pattern does not always mean tandem fusion, but can be interpreted as 'tandem fission' by a combination of AM-inversion and centric fission. Tandem fusion and MM-inversion often cause entangled matching patterns, and thus they interfere with banding pattern analysis. Some methodological problems inherent in the conventional banding pattern analysis are highlighted, and suggested that such problems can be minimized by using the karyograph method. The methodology of banding pattern analysis proposed in the present paper will be applicable for matching the chromosome map of genetic markers among different species. PMID- 8369140 TI - Sliding toward nutrition malpractice: time to reconsider and redeploy. PMID- 8369141 TI - Nutritional management of cystic fibrosis. PMID- 8369142 TI - Recent advances in mammalian amino acid transport. AB - During the last four decades, mammalian amino acid transport systems have been described at the cellular level through general properties such as ion dependence, kinetics, substrate specificity, regulation of activity, and numerous other characteristics. These studies have allowed the definition of multiple transport systems for neutral, anionic, and cationic amino acids. Each system is distinct but exhibits overlapping substrate specificity. Direct measurement of transport has permitted a wealth of information to be accumulated regarding the regulation of overall activity, but the underlying molecular mechanisms have not been investigated because of a lack of the appropriate tools. Recent research designed to obtain these tools has proven fruitful, and the field of amino acid transport clearly is entering a new era. In the immediate future, transporter properties such as hormonal regulation, adaptive control, ion-dependence, and trans-effects will be studied at the molecular level by assaying mRNA or protein content and by analyzing results obtained with altered protein structures following site-directed mutagenesis. Identification of specific proteins associated with activities already well described will provide answers to heretofore untestable questions. For example, is Na(+)-independent transport mediated by the same proteins that mediate Na(+)-dependent uptake except that their function in this mode does not require sodium binding? What is the protein composition of amino acid transporters? As discussed above, emerging evidence suggests that transporter proteins have different molecular structure, 12 versus 1 transmembrane domains, or that they exist as heterodimers or heterotetramers. Identification of certain transporter proteins and cloning of the respective genes also will provide valuable information about a number of inheritable diseases that are thought to be caused by defects in transporter synthesis or function. The opportunity to ask these questions will certainly generate renewed interest in the field of amino acid transport and lead to exciting advances in our knowledge. PMID- 8369143 TI - Fungal toxins in foods: recent concerns. PMID- 8369144 TI - Biosynthesis and function of enzymes with covalently bound flavin. PMID- 8369145 TI - Impact of plant genetic engineering on foods and nutrition. PMID- 8369146 TI - Biological effects of short-chain fatty acids in nonruminant mammals. PMID- 8369147 TI - Effects of polyunsaturated fats on blood pressure. PMID- 8369148 TI - Nutritional factors in osteoporosis. PMID- 8369149 TI - Biological nitrogen fixation. PMID- 8369150 TI - Genetics of obesity. PMID- 8369151 TI - Regulation of plasma LDL-cholesterol levels by dietary cholesterol and fatty acids. AB - Extensive data obtained in both experimental animals and humans demonstrate that steady-state plasma LDL-C concentrations are determined largely by the rate of LDL-C formation, Jt, and the level of LDL-R activity, Jm, located primarily in the liver. An increase in net cholesterol delivery to the liver suppresses Jm, slightly elevates Jt, and modestly raises the LDL-C level. Feeding lipids such as the 12:0, 14:0, and 16:0 saturated fatty acids further suppresses Jm, increases Jt, and markedly elevates the plasma LDL-C concentration. Feeding triacylglycerols containing the 18:1(c9) fatty acid restores hepatic receptor activity, decreases Jt, and modestly reduces the concentration of LDL-C in the plasma. The 18:2(c9, c12) compound has similar effects, although it is quantitatively less active than the monounsaturated fatty acid in restoring Jm. In contrast to these fatty acids that actively raise or lower hepatic receptor activity, a large group of compounds including the 4:0, 6:0, 8:0, 10:0, 18:0, and 18:1(t9) fatty acids have no demonstrable effect on any parameter of LDL-C metabolism. These fatty acids, therefore, can be added to animal and human diets with relative impunity. They will alter plasma LDL-C levels only to the extent that they replace the active saturated fatty acids (in which case they lower the LDL-C concentration) or unsaturated compounds (in which case they raise the plasma cholesterol level). All of these effects of cholesterol and the various fatty acids can be explained by the effects of these lipids in altering the size of the regulatory pool of cholesterol in the hepatocyte. However, many aspects of the cellular and molecular biology of these regulatory processes require additional investigation. In particular, new studies should focus on how the genetic background of an individual animal or human alters the quantitative response of its plasma LDL-C concentration to the dietary challenge of each of these types of lipids. PMID- 8369152 TI - Clinical physiology of taste and smell. PMID- 8369153 TI - Aluminum metabolism. PMID- 8369154 TI - Effects of exogenous bovine somatotropin on lactation. PMID- 8369155 TI - Mammalian glucokinase. PMID- 8369156 TI - Regulation of the pyruvate dehydrogenase multienzyme complex. PMID- 8369157 TI - Iron deficiency and cognitive function. PMID- 8369158 TI - Lipid modulation of cell function. PMID- 8369159 TI - Actions of carotenoids in biological systems. PMID- 8369160 TI - Regulation of selenoproteins. AB - Selenium exerts its biological activity largely through selenoproteins, which contain the element in the form of selenocysteine. Five selenoproteins have been characterized in animal tissues and there is evidence that a number of others exist. Selenoprotein synthesis is a complex process that has been well characterized in prokaryotic systems but incompletely characterized in eukaryotic systems. Selenium deficiency causes a decrease in selenoproteins, but the decrease is not uniform and some selenoproteins are maintained better than others. The selenoprotein most sensitive to selenium deficiency is liver cGSH-Px. It contains a significant fraction of the selenium in the body, and decreased synthesis of it under deficiency conditions might serve to increase the selenium available for synthesis of selenoproteins that are more important to the survival of the animal than is cGSH-Px. The regulation of individual selenoproteins in selenium deficiency appears to be at the mRNA level. Factors that affect mRNA levels have not been completely characterized, but the fall in cGSH-Px mRNA in rat liver is not accompanied by decreased transcription, which suggests that it is regulated through changes in degradation. PMID- 8369161 TI - Nutritional management of glycogen storage disease. PMID- 8369162 TI - Synergistic inhibition of HIV-1 envelope-mediated cell fusion by CD4-based molecules in combination with antibodies to gp120 or gp41. AB - CD4-based molecules were tested in combination with HIV-1-neutralizing antibodies directed against the V3 loop of gp120 or against gp41, for inhibition of HIV-1 envelope-mediated cell fusion. A virus-free cell fusion assay was developed, using Chinese hamster ovary cells that stably express HIV-1 gp120/gp41. These cells were incubated with dilutions of CD4-based molecules, antibodies, or mixtures of both, then overlaid with C8166 CD4+ T cells. Syncytia were counted and the degree of inhibition of cell fusion was determined. Synergy, additivity, or antagonism was calculated by the combination index (CI) method. The CD4-based molecules included soluble human CD4 as well as fusion proteins composed of CD4 linked to human immunoglobulin gamma 1 or gamma 2 heavy chains. Combinations of CD4-based molecules and monoclonal or polyclonal anti-V3 loop antibodies were synergistic in blocking HIV-1 envelope-mediated cell fusion (CI = 0.21-0.91 at 95% inhibition). Synergy was also observed with combinations of the CD4-based molecules and a broadly neutralizing anti-gp41 monoclonal antibody (2F5) (CI = 0.29-0.65 at 95% inhibition). These results demonstrate that molecules inhibiting HIV attachment act synergistically with molecules inhibiting HIV-1 fusion. The results suggest that CD4-based therapeutics would be more effective in patients with naturally occurring anti-V3 loop or anti-gp41 antibodies. In addition, there may be an advantage in coadministering CD4-based molecules and antibodies that block fusion, especially broadly neutralizing anti-gp41 antibodies, as a combination therapy for HIV-1 infections. PMID- 8369163 TI - Mutational analysis of the assembly domain of the HIV-1 envelope glycoprotein. AB - The amino-terminal 129 amino acids of gp41 of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein constitute the assembly domain required for efficient oligomer formation and stability. Point mutations in highly conserved structural features including cysteine residues, potential N linked glycosylation sites, and a leucine zipper motif have been made in a soluble secreted form of Env (Envsec). No single point mutation had adverse effects on Env protein oligomerization. However, truncation of the C terminus of gp41 from 129 amino acids to 68 amino acids drastically reduced oligomerization efficiency, indicating that amino acids 68-129 are essential for assembly. PMID- 8369164 TI - Soluble CD4 and CD4 immunoglobulin-selected HIV-1 variants: a phenotypic characterization. AB - The selection of HIV-1 resistance to neutralization by both monovalent and bivalent forms of soluble CD4 was demonstrated under various conditions. Phenotypic traits of the neutralization-resistant variants were systematically explored in order to gain insight into which aspects of the interactions with CD4 are most expendable to HIV-1 replication. The size of the nonneutralized fraction after treatment of preparations of the HIV-1 isolate IIIB and a molecular clone derived from it (HX10), with either monovalent soluble CD4 (sCD4) or bivalent CD4 Ig, was determined. These fractions were greater for the polyclonal IIIB than for the viral clone, and greater after treatment with sCD4 than with CD4-Ig. The virus in the nonneutralized fractions exhibited 2- to 20-fold lower sensitivity to the neutralizing agents than did unselected virus. In addition, clonal HIV-1 (HX10) was cultured in the presence of sCD4 or CD4-Ig for 12 weeks, so as to allow for accumulation of mutations that would confer stronger resistance to the selecting agent. Variants were obtained with up to 100-fold increased resistance to sCD4 or CD4-Ig. Detergent-solubilized gp120 from sCD4- and CD4-Ig-selected virus showed decreases in affinity for sCD4 and CD4-Ig. The monoclonal antibodies 6H10, to the gp120-binding site in domain 1 of CD4, and 5A8, to domain 2 of CD4, inhibited the induction by the viral escape variants of syncytium formation of C8166 cells. In general, the concentration of antibody 6H10 that inhibited the escape variants was lower than the concentration that inhibited the wild type, whereas there was no significant difference for the domain 2 antibody 5A8. We interpret this as a weaker attachment of the escape variants than of the wild type virus to cellular CD4, but as an intact dependence of the variants on CD4 interactions for gaining entry into cells. PMID- 8369165 TI - A hidden region in the third variable domain of HIV-1 IIIB gp120 identified by a monoclonal antibody. AB - The third variable domain (V3 domain) of HIV-1 gp120 is involved in virus neutralization by antibody, in determination of cell tropism, and in syncytium inducing/non-syncytium-inducing capacity. Antibodies are highly specific tools to delineate the role of different V3 amino acid sequences in these processes, and to dissect events occurring during synthesis of gp120/160, gp120-CD4 interaction, cellular infection, and syncytium formation. We describe here an IgG1 murine monoclonal antibody (MAb), coded IIIB-V3-01, that was raised with a synthetic peptide (FVTIGKIGNMRQAHC) derived from the carboxy-terminal flank of the HIV-1 IIIB V3 domain. The binding site of this antibody was mapped to the sequence IGKIGNMRQ, using Pepscan analysis. In ELISA, this antibody binds to E. coli derived gp120 from HIV-1 IIIB, which is denatured and not glycosylated. The antibody showed no neutralizing activity against HIV-1 IIIB, MN, SF2, or RF in a virus neutralization assay and in a syncytium formation inhibition assay. In addition, this antibody did not react with gp120 expressed on the surface of IIIB infected MOLT-3 cells in FACS analysis. To assess whether the epitope defined by MAb IIIB-V3-01 is hidden on native gp120, reactivity of the antibody with SDS-DTT denatured or DTT-denatured glycosylated gp120 (CHO cell produced) was tested. Both these treatments exposed the epitope for binding. From these data we conclude that the epitope defined by MAB IIIB-V3-01 is hidden on glycosylated recombinant gp120, and is not accessible on gp120 expressed on the membrane of HIV-1, IIIB-infected cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369166 TI - Genetic diversity of human immunodeficiency virus type 1 strains in Kinshasa, Zaire. AB - The envelope (env) gene of human immunodeficiency virus type 1 (HIV-1) was amplified by polymerase chain reaction (PCR) from the peripheral blood mononuclear cells (PBMCs) of 14 HIV-1-infected women from Kinshasa, Zaire. Amplified DNA was directly sequenced with a primer specific for the HIV-1 env C2 region. The predicted amino acid sequences for the C2-V3 region for the 14 specimens are presented. The tetrapeptide sequence, GPGQ, located at the crown of the V3 loop, is conserved in all specimens. The same tetrapeptide sequence is present in the Zairian isolate MAL, but not in other published Zairian isolates (Z6, ELI, Z321, JY1, and NDK). Sequence comparison of the env C2-V3 region among the 14 specimens from Kinshasa revealed a 9-25% range of nucleotide divergence, with an average of 16%. Divergence between the 14 specimens and the Zairian isolates MAL, Z6, ELI, Z321, JY1, and NDK ranged from 13 to 31%. A range of 18 28% nucleotide sequence divergence was demonstrated between the 14 Kinshasa specimens and the North American isolate MN. These results demonstrate the importance of examining HIV-1 samples from diverse geographic origins in the development of effective HIV-1 vaccines. PMID- 8369167 TI - Complement-dependent virolysis of HIV-1 with monoclonal antibody NM-01. AB - Previous studies have described the isolation of monoclonal antibodies that neutralize human immunodeficiency virus type 1 (HIV-1). However, although certain antibodies are capable of blocking infection of CD4+ cells, the antibody-HIV-1 complex could potentially remain infectious and enter cells by an Fc receptor mediated mechanism. Indeed, one goal of HIV-1 therapy with antibodies is the development of reagents capable of killing virus. The present studies with murine monoclonal antibody (MoAb) NM-01 demonstrate complement-mediated lysis of HIV-1. NM-01-dependent virolysis has been visualized by electron microscopy. Virus particles treated with NM-01 and rabbit or human complement undergo a process of outer envelope rupture and loss of the electron-dense core. The involvement of human complement in this process was confirmed by the presence of C9 in association with MoAb NM-01 immune complexes. In contrast, virolysis was not detectable with antibody or complement alone. Moreover, although MoAb NM-01 alone is capable of neutralizing HIV-1, the presence of rabbit complement was associated with over a 10-fold decrease in infectivity. Similar but less pronounced effects were observed with human complement. These findings support a potential role for antibody-dependent complement-mediated virolysis in HIV-1 therapy. PMID- 8369168 TI - Antibodies to recombinant gp160 in mucosal secretions and sera of persons infected with HIV-1 and seronegative vaccine recipients. AB - An enzyme immunoassay (EIA) was developed to detect secretory IgA (sIgA) antibodies to HIV-1 envelope glycoprotein, using a mouse monoclonal antibody and a highly purified, baculovirus-expressed recombinant gp160 (rgp160) as antigen. Detection of sIgA was enhanced by prior immunoprecipitation of IgG. IgG and sIgA rgp160 antibodies were measured in parotid saliva and nasal wash samples of 18 HIV-1-seropositive volunteers and 14 HIV-1-seronegative adult volunteers immunized 3 times with HIV-1 IIIB rgp160 vaccine at 1 of 4 dosage levels: 40 micrograms (N = 3), 80 micrograms (N = 3), 160 micrograms (N = 4), and 640 micrograms (N = 4). We detected rgp160-specific IgG antibody in the nasal wash samples of all HIV-1-seropositive volunteers and 4/8 vaccinees (50%) immunized with the two highest doses of rgp160 vaccine. All infected volunteers tested had rgp160-specific sIgA in their nasal wash samples. None of the vaccinees and very few of infected volunteer specimens had detectable antibody in the parotid saliva samples (5/8 had IgG and 1/8 had sIgA). We also detected IgG antibody to rgp160 in the sera of all infected volunteers and 13/14 vaccinees (93%). With this EIA, sIgA antibody can be measured in mucosal secretions of recipients of appropriate candidate HIV-1 vaccines. PMID- 8369169 TI - The impact of HIV-1 infection on phenotypic and functional parameters of cellular immunity in chimpanzees. AB - As a means of assessing the immunological impact of HIV infection in the chimpanzee, as well as the participation of the cellular components in the control of HIV infection in these animals, various aspects of cellular immunity were investigated in chronically HIV-infected chimpanzees. Eight HIV-1-infected chimpanzees were included in this study; two of them were infected for more than 5 years and six for nearly 3 years at the time of study. All of the chimpanzees received either 40 or 100 TCID50 of HTLV-IIIB. Circulating peripheral blood lymphocytes were studied by flow cytofluorimetric analysis in order to reveal possible alterations in the CD4:CD8 ratio, as well as in specific CD4+ and CD8+ cell subpopulations. Chronically infected chimpanzees did not present significant alterations in the percentage of CD4+ or CD8+ lymphocyte subsets. Interestingly, the CD8+/CD57+ cell subset was not detectable. The expression of markers for activation on circulating lymphocytes, usually higher in the HIV-infected patients, was not altered in infected animals. The functional aspects of specific anti-HIV-1 non-MHC and MHC-restricted cellular cytotoxic reactivities were also investigated. The results were compared with the findings in normal uninfected chimpanzees and in HIV-infected humans. Only one chimpanzee (881) developed a detectable, specific non-MHC-restricted anti-HIV-1- reactivity. Compared to that seen in humans, the ontogeny of this activity is delayed. Among the other infected chimpanzees, no specific anti-HIV cellular reactivities were detectable in the peripheral blood. In chimpanzees, HIV-1 infection evidently does not elicit the same strong cellular reactivity as that detected in infected patients. The absence of chronic cellular activation, despite continued viral replication, may highlight a key determinant in HIV-1-induced pathogenesis that is likewise absent in infected chimpanzees. PMID- 8369170 TI - Progressive impairment of monocytic function in HIV-1-infected human macrophage hybridomas. AB - Using human macrophage hybridomas infected with HIV-1, we investigated monocyte function over a 5-week period after HIV-1 infection. Two clones, 63 and 30, were infected with HIV-1IIIB. Infection was documented by RT activity (15 x 10(6) cpm/ml), intracytoplasmic staining with an anti-p24 antibody, in situ hybridization with an HIV-1-specific riboprobe, and electron microscopy showing intracytoplasmic virus. Two weeks after infection, clones 63 and 30 lost expression of all class II antigens (DR, 81.7 vs. 0%; DQ, 15.6 vs. 0%; and DP, 76.9 vs. 0%) while retaining expression of class I (87.4 vs. 84.1%), LFA-1 (82.4 vs. 83.1%), and LFA-3 (79.1 vs. 74.7%) antigens when compared to uninfected cells. When tested for functional integrity, infected but not uninfected clone 63 cells failed to stimulate a tetanus-specific MHC-restricted T cell proliferative response 2 weeks after infection. Cytokine secretion and antigen processing were also perturbed as production of IL-1 was abolished 2 weeks after infection (although IL-6 secretion was augmented) and infected clone 63 cells failed to process exogenous antigen. Last, the viability of T cells cocultured with infected clone 63 was dramatically decreased 35 days after infection (85 vs. 15%). There was no evidence of transmission of HIV-1 to T cells, suggesting a toxic effect of infected clone 63. Taken together, these data suggest that altered macrophage function in our system occurs at multiple levels, which may account for the early immunological defects described in HIV-1 infection. PMID- 8369171 TI - Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism. AB - The expression of human immunodeficiency virus type 1 (HIV-1) is enhanced after cell activation because of the interaction of cell-encoded nuclear factors that interact with binding sites in the long terminal repeats (LTRs). Here we studied the contribution of cell type-specific activation signals to differences in cytotropism of HIV-1 variants. Four closely related molecular HIV-1 clones with distinct biological phenotypes and different capacities to replicate in primary monocyte-derived macrophages (MDMs) or T cell lines were used. Sequence analysis of these LTRs revealed variation in functionally important regions. Adaptation of virus variants to particular host cells by differences in LTR responsiveness was analyzed. LTR-CAT constructs were transiently transfected in T cells that were stimulated with T cell-specific activation signals such as combinations of anti CD3 or anti-CD28 MoAB or in primary monocytes that were stimulated with IL-3, IL 4, or GM-CSF. No differences in responsiveness to cell type-specific signals were demonstrated. To further elucidate the level of restriction in cell tropism, transfection of four full-length infectious molecular HIV-1 clones into 5-day cultured MDMs was performed. From all clones, competent virus could be rescued from MDMs by coculture with PHA-stimulated PBLs. However, following cell-free inoculation, proviral DNA could be detected by PCR analysis only in monocytes exposed to HIV-1 clones that previously were shown to establish productive infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369172 TI - HIV-1 Tat alters normal organization of neurons and astrocytes in primary rodent brain cell cultures: RGD sequence dependence. AB - The HIV-1 trans-activator protein Tat has been implicated as a mediator of neuronal dysfunction in several model systems. To explore the possibility that Tat can affect primary brain cells, we examined the effect of recombinant Tat protein on rat cortical brain cell cultures. Tat induced marked aggregation of neurons and astrocytes in developing cultures and caused the neuritic processes to coalesce into fascicles. Cell death was not seen and brain macrophages were not affected. These effects mapped to a different region from the trans activation domain of Tat, as mutating the RGD (arginine-glycine-aspartic acid) sequence within the second exon abrogated aggregation and fascicle formation without affecting trans-activation capacity. Such effects on primary neurons and astrocytes may reflect specific interactions of Tat with uninfected cells within the CNS in vivo. PMID- 8369173 TI - Monoclonal antibodies to HIV-1 gp120: a request. PMID- 8369174 TI - Assimilating HIV sequences. PMID- 8369175 TI - Genetic typing of HIV-2 from a Senegalese/German heterosexual transmission. PMID- 8369176 TI - V3 loops of HIV-1 specimens from pregnant women in Malawi uniformly lack a potential N-linked glycosylation site. PMID- 8369177 TI - Digital radiography. A useful clinical tool for computer-aided diagnosis by quantitative analysis of radiographic images. PMID- 8369178 TI - Digital luminescence radiography using a chest phantom. Comparison between radiographs displayed on monitor at a workstation and at a personal. AB - With the introduction of picture and archiving communicating systems an alternative image display for the wards might be a personal computer (PC). The intention with this study was to evaluate the diagnostic image quality of the monitor of a PC compared to that of a workstation. Eighty-five digital radiographs of a chest phantom with simulated tumors in the mediastinum and right lung were saved on optical discs. The examination were reviewed by 4 radiologists on a monitor at a workstation and at a PC, and receiver operating characteristic (ROC) curves were constructed. No significant difference was found between performance of the PC and the workstation. PMID- 8369179 TI - Advanced multiple beam equalization radiography (AMBER) combined with computed radiography. Preliminary evaluation. AB - The combined use of AMBER (Advanced Multiple Beam Equalization Radiography) and a digital storage phosphor (SP) radiography system was evaluated for chest radiography in a pilot study with 4 patients. Four image modes with different dose levels were compared: the SP in combination with an AMBER equalized exposure (SP/AMBER) and 3 nonequalized exposures with dose levels corresponding to the respective calculated AMBER lung dose (SP/lung field dose), the calculated AMBER mediastinal dose (SP/mediastinal dose) and the calculated AMBER average dose (SP/average dose). All image modes were matched for Hurter and Driffield characteristics and subjectively rated according to visibility of details. The improved signal-to-noise (S/N) ratio of SP/AMBER resulted in a better visualization of structures in the mediastinum and the basal lung where SP/lung field dose scored lowest. For the central lung no quality differences were seen between techniques. The compressed dynamic range of the SP/AMBER images was more easily displayed on the hard-copy film. The combination of AMBER with SP radiography promises to overcome the dynamic range limitations of digital displays while, at moderate doses, giving better S/N and image quality than standard SP technique. PMID- 8369180 TI - Normal left ventricular wall motion measured with two-dimensional myocardial tagging. AB - Using a myocardial tagging technique, normal left ventricular wall motion was studied in 3 true short axis views and a double oblique 4-chamber view in 14 and 11 volunteers, respectively. Three orthogonal directions of left ventricular motion were observed throughout the systole; a concentric contraction towards the center of the left ventricle, a motion of the base of the heart towards the apex, and a rotation of the left ventricle around its long axis. The direction of left ventricular rotation changed from early systole to late systole. The base and middle levels of the left ventricle rotated counterclockwise (CCW) at early systole and clockwise (CW) at late systole, whereas the apex of the heart rotated CW at early systole and CCW at late systole. The different directions of the rotation of base and apex resulted in a myocardial twisting that changed direction from early to late systole. We conclude that MR imaging with myocardial tagging is a method that can be used to study normal left ventricular wall motion, and that is promising for future use in patient groups. PMID- 8369181 TI - Target delineation in radiosurgery for cerebral arteriovenous malformations. Assessment of the value of stereotaxic MR imaging and MR angiography. AB - A study of 6 selected arteriovenous malformation (AVM) patients was performed to investigate the feasibility of delineating an AVM on MR images and to compare the AVM volume outlined on different images. Conventional stereotaxic angiograms, stereotaxic MR images and MR angiograms using several different pulse sequences were obtained prior to radiosurgery. Treatment plans were made from the conventional stereotaxic angiograms. These plans were then transferred to a separate dose planning computer which displayed the MR images with the superimposed isodose lines. The radiated volumes of AVM and brain tissue were measured from these MR images. Last, an assessment was made of the radiation volume needed for an appropriate treatment of the AVM if the treatment plan was made from the MR images rather than from the conventional stereotaxic angiogram. It was possible to delineate medium and large size AVM nidi on stereotaxic MR images based on an integration of information obtained from various pulse sequences. The estimated volumes of the AVM nidi were found to be larger on the conventional stereotaxic angiograms than on the stereotaxic MR images. Consequently, a dose plan based on a conventional stereotaxic angiogram would result in a higher integral dose to the brain with the same target dose. By using reliable MR information it is expected that the volume of brain exposed to radiation could be decreased and the adverse effects of stereotactic radiosurgery for AVM thereby minimized. PMID- 8369182 TI - Intramedullary nailing and cortical bone mineral content. Photon absorptiometry measurements in vitro. AB - A transverse diaphyseal osteotomy of the tibia was stabilized using rigid intramedullary nailing in rabbits. In a 2nd group, nailing was performed without osteotomy. The rabbits were sacrificed 3 to 24 weeks postoperatively, and the nails were removed. The mineral content (BMC) was measured by dual photon absorptiometry and the mineral density (BMD) was calculated. At 24 weeks the osteotomized bones had significantly lower BMC values than did the respective nonosteotomized bones or the intact bones. The BMC of the nonosteotomized bones remained above the control level throughout the experiment. The minimum BMD values of the osteotomized bones were detected at 3 weeks, whereafter they gradually approached the control level over time. The results suggest that rigid intramedullary nailing in connection with osteotomy causes a significant decrease in cortical bone mineral mass, seen at 24 weeks postoperatively. The photon absorption method used seemed sensitive enough to detect changes in cortical bone mineral quantity in these experimental conditions. PMID- 8369183 TI - Ultrasound-guided biopsies of neuroendocrine metastases. Comparison of 0.9 and 1.2 mm biopsy-gun needle biopsies. AB - Twenty-five patients with known neuroendocrine tumour disease were biopsied with 1.2 mm and 0.9 mm biopsy-gun needles to evaluate the respective diagnostic accuracy of the 2 needle sizes. The influence of treatment-related fibrosis on the histopathological diagnosis was also evaluated. The overall diagnostic accuracy with the 0.9 mm needle was 69% as compared to 92% with the 1.2 mm needle. This difference, however, seems more related to needle guiding difficulties with the 0.9 mm needle than to insufficient tissue yield. When the tumour was hit with both the 0.9 and the 1.2 mm needle the tissue yield was inferior with the 0.9 mm needle in only one of 16 cases. The increased amount of fibrous tissue due to interferon treatment did not seem to negatively influence the diagnostic accuracy. PMID- 8369184 TI - Duplex ultrasonographic evaluation of liver transplants. AB - Two hundred and twenty-two duplex ultrasonographic examinations were performed on 36 liver transplants in 30 patients over a period of 5 years and 9 months. Positive sonographic findings were correlated with 13 angiographic examinations. Arterial complications included 4 thromboses, 5 stenoses, and one mycotic aneurysm. A false-negative result was obtained in 2 cases of stenosis and a false positive result in one case of thrombosis. One portal vein thrombosis, 2 stenoses, and 2 cases of portal hypertension were diagnosed correctly. Sensitivity was 87%, specificity 95%, and accuracy 93%. Duplex Doppler was least effective in the diagnosis of hepatic artery stenosis. Five cases showed biliary complications of ischemic origin. Angiography is indicated when duplex Doppler is positive or doubtful, but also when the clinical condition is unclear. PMID- 8369185 TI - Sonographic evaluation of renal appearance in 665 adult volunteers. Correlation with age and obesity. AB - The purpose of this study was to investigate the sonographic appearance of the normal adult kidney. Parenchymal echogenicity, pyramid visibility, and transverse pelvis diameter of the kidneys were prospectively determined in an age- and sex stratified random sample of 665 volunteers 30, 40, 50, 60, and 70 years old. Furthermore, incidences of kidney stones and split sinus echo were determined. The relation between obesity and above-mentioned parameters was evaluated. In the 30-year-old age group the right kidney was isoechoic as compared to the liver in 1/3, and had clearly or faintly visible pyramids in 2/3 of the cases. These rates decreased gradually with increasing age. Transverse diameter of renal pelvis > or = 10 mm was observed in 13% of participants. Renal stones were observed in 2.1%. The incidence of split sinus echo was 3.6%. Obese participants showed lower incidences of isoechogenicity, pyramid visibility, pelvic ectasia, and split sinus echo. Isoechoic parenchyma, clearly visible pyramids, and transverse pelvis diameter > or = 10 mm are not uncommon sonographic findings in normal adult kidneys and should not be used as indicators of renal pathology. PMID- 8369186 TI - The kissing balloons technique. Simultaneous dilatation of stenoses of branch arteries at the bifurcation of the renal artery. AB - Whereas dilatation of a single stenosis of the main renal artery is a routine intervention, a narrowing of the renal artery at its bifurcation extending into the branch arteries poses a more complex problem. The procedural risks of renal artery dilatation are compounded by the danger of occlusion of one of the branch arteries during maneuvers to dilate the other. Long-term results of surgical vascular reconstruction at a renal artery bifurcation are not satisfactory. Untreated, these stenoses lead to intractable hypertension and impairment or loss of renal function. We present a patient with hypertension and impaired function of the right kidney on account of a renal arterial bifurcation stenosis. Using a bilateral transfemoral arterial approach 2 balloon catheters were simultaneously placed into the origins of the renal artery branches and both arteries were successfully dilated by the kissing balloons technique. This method provides an elegant alternative to difficult surgery to save an endangered kidney. PMID- 8369187 TI - Reactive mediastinal lymphadenopathy in bronchiectasis assessed by CT. AB - Mediastinal lymphadenopathy is commonly detected on CT. It is a non-specific finding, but because of its significance in the treatment in lung carcinoma it is important to know with which other disease states it is associated. We present a series of 42 patients in whom CT of the chest was used to confirm a clinical diagnosis of bronchiectasis. The size, number and distribution of mediastinal lymph nodes is documented. Lymph nodes were visible in 81% of patients. Nodes larger than 10 mm, the recognised maximum size for normal nodes in the U. K., were detected in 29%. In the absence of other recognised causes of lymphadenopathy in these patients, these findings confirm "reactive" mediastinal lymph node enlargement in bronchiectasis. PMID- 8369188 TI - Carpet-layer's knee. An ultrasonographic study. AB - In order to reveal abnormalities in the soft tissue of the anterior part of the knee, caused by protracted mechanical stress, we performed ultrasound studies of both knees of 95 male workers in the carpet-laying and parquet floor trade (group 1). Seventy-three painters (group 2) served as controls. In group 1, an anechoic fluid collection was detected in 10 knees, localized in the superficial infrapatellar bursa and in one patient in the prepatellar bursa, whereas there were no cases of fluid accumulation in the controls. A hypoechoic, oval subcutaneous thickening in the anterior wall of the superficial infrapatellar bursa was detected in 35 (18.4%) and 4 (2.7%) knees, respectively. Prepatellar subcutaneous thickening was detected in 45 knees (23.7%) in group 1, but in only 2 knees (1.4%) in group 2. Two knees in group 1 had thickened and inhomogeneous patellar tendons, while one in group 2 had a thickened and 2 both thickened and hypoechoic patellar tendons. We conclude that ultrasonography is a useful method for the detection of bursitis and soft tissue changes in carpet-layers. Detection of a fluid collection in a bursa does not necessarily denote bursitis of clinical importance, but does signify irritation due to work stress. Patellar tendon pathology is rare among carpet-layers and is probably unrelated to the occupation. PMID- 8369189 TI - In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part III. Effects of mannitol and iohexol infusions after pretreatment with cyclosporin A. AB - In vivo fluorescence microscopy was used for experimental studies of the renal cortical microcirculation in normal mice and in mice pretreated with the nephrotoxic drug cyclosporin A. The cortical circulation was studied after i.v. infusions of a nonionic low osmolar contrast medium (iohexol) and after infusions of mannitol. All infusions produced marked effects on the distribution and velocity of cortical blood flow with no differences between iohexol and mannitol. The renal cortical blood flow was inhomogeneous regarding different capillaries and there was an initial rise in the number of capillaries with increased blood flow after infusions of both mannitol and iohexol. There was simultaneously an increased number of capillaries with decreased blood flow following all infusions. The decreased blood flow after infusion of iohexol was more pronounced when the animals had been pretreated with cyclosporin A. The difference was only significant (p < 0.05) during a short part of the observation period of 30 min, but it may indicate that kidneys previously exposed to cyclosporin A are more susceptible to infusions of iohexol. PMID- 8369190 TI - In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part IV. Effects of mannitol and iohexol infusions after temporary renal ischemia. AB - In vivo fluorescence microscopy was used for experimental studies of the renal cortical microcirculation in mice. The effects of i.v. infusions of mannitol and iohexol were studied in untreated mice as well as in mice after temporary renal ischemia. All infusions produced marked effects on the distribution and velocity of cortical blood flow with no differences between iohexol and mannitol. The renal cortical blood flow was inhomogeneous with respect to different capillaries and there was an initial rise in the number of capillaries with increased blood flow after infusions of both mannitol and iohexol. There was an initial increase in the number of capillaries with a decreased blood flow following 30 min of ischemia. This increase was reduced by both types of infusions, suggesting a beneficial effect on renal cortical blood flow. Neither mannitol nor contrast medium exhibited any adverse effects in ischemic kidneys that would be likely to affect renal function. However, 5 min after the infusions there was an increasing number of capillaries with decreased blood flow in all groups. PMID- 8369191 TI - Hemodynamic effects of gadodiamide injection and gadopentetate dimeglumine in anesthetized dogs. AB - A nonionic (gadodiamide injection) and an ionic (gadopentetate dimeglumine) contrast medium were compared for their effect on hemodynamics in the anesthetized, open-chest dog. Both agents were administered i.v. over 15 s at dosages of 1.0 and 1.5 mmol/kg, in randomized order. Both contrast agents resulted in transient but statistically significant decreases in aortic pressure, left ventricular pressure, indices of left ventricular contractility and relaxation, and systemic and pulmonary vascular resistance, and increases in aortic blood flow. At each dosage investigated, the changes associated with the administration of gadodiamide injection were of significantly smaller magnitude than those seen after gadopentetate dimeglumine and returned to preadministration levels sooner. The results from this study confirm that gadodiamide injection produces less severe alterations in hemodynamics than gadopentetate dimeglumine. PMID- 8369193 TI - MR appearance of central neurocytoma. AB - To provide a detailed description of the MR appearances of central neurocytoma, MR images of 13 patients with central neurocytoma were retrospectively reviewed and compared with CT examinations. The histology was confirmed by ultrastructural and immunohistochemical studies. In 12 patients the tumors were histologically benign and located in the anterior part of the lateral ventricle, 6 of which extended to the 3rd ventricle. There was one case of a histologically malignant variant involving the thalamus and lateral ventricle. The tumors were primarily solid, but contained cysts (85%, 11/13), calcifications (69%, 9/13), and signal void from tumor vessels (62%, 8/13), frequently producing heterogeneous signal intensity on both T1- and T2-weighted images. Most of the solid portion appeared isointense or slightly hyperintense relative to the cerebral cortex on all MR pulse sequences. Calcifications were iso- or hypointense on MR, making them difficult to characterize with MR alone. Intratumoral hemorrhage was seen in 2 patients on MR but not on CT. Contrast enhancement was variable in degree and pattern. Coronal and sagittal MR images were valuable in evaluating the tumor extent and origin site, and in planning the surgical approach. It is concluded that MR imaging appears to be more useful than CT in the overall evaluation of central neurocytoma, even though calcification is better characterized with CT. PMID- 8369192 TI - Oral contrast media in CT of the abdomen. A double-blind randomized study comparing an aqueous solution of amidotrizoate, an aqueous solution of iohexol and a viscous solution of iohexol. AB - In a double-blind randomized study 3 different preparations of oral contrast media for bowel opacification at CT of the abdomen have been compared. Plain aqueous solutions of amidotrizoate (9 mg I/ml) and iohexol (9 mg I/ml) were used as well as a preparation of iohexol (9 mg I/ml) to which a viscosity-increasing agent had been added. The distribution of the contrast media in the intestine, transit time and patient tolerance were evaluated. No significant differences were found regarding the distribution between the 3 preparations of contrast media, while there was a tendency for the transit time to be increased when the viscous preparation of iohexol was used. The aqueous solution of iohexol had the best taste, while the viscous preparation was markedly more difficult to drink. Aqueous solutions of iohexol and amidotrizoate were equal for bowel opacification and the addition of the viscosity-increasing agent did not improve the distribution of the contrast medium in the intestine. PMID- 8369194 TI - MR imaging of monostotic fibrous dysplasia of the clivus. A case report. AB - We describe the MR appearance of a case of monostotic fibrous dysplasia confined to the clivus. The lesion showed intermediate signal intensity on T2-weighted images which is uncommon among clival diseases. PMID- 8369195 TI - Audiogenic seizures in magnesium-deficient mice: effects of magnesium pyrrolidone 2-carboxylate, magnesium acetyltaurinate, magnesium chloride and vitamin B-6. AB - Magnesium deficiency in mice causes and increases audiogenic seizures. This effect was reversed by oral administration of magnesium acetyltaurinate (ATaMg), magnesium pyrrolidone-2-carboxylate (PCMH), MgCl2. When treatment was discontinued, audiogenic seizures recurred only in the groups treated with PCMH or MgCl2. Following intraperitoneal administration of AtaMg, the mice were protected against audiogenic seizures after 4 h and this protection persisted for up to 72 h after the treatment. With the other magnesium salts (PCMH and MgCl2) maximum protection occurred by 6 h after the injection, but after that time the number of seizures increased sharply. Intraperitoneal taurine alone only reduced the severity of the audiogenic seizures. The length of treatment needed to inhibit audiogenic seizures was reduced by treatment with a combination of vitamin B-6 (a magnesium fixing agent) and PCMH or MgCl2. However this combination of vitamin B-6 and magnesium salts did not prevent the recurrence of audiogenic seizures, which was only achieved by ATaMg. The results suggest that audiogenic seizures in magnesium-deficient mice form a model of magnesium depletion. This depletion is completely inhibited by the combination of an inhibitory neurotransmitter (taurine) and magnesium, in the form of magnesium acetyltaurinate. PMID- 8369196 TI - Brain weight and noradrenaline content in mice selected for low (MGL) and high (MGH) blood magnesium. AB - Brain noradrenaline content was determined by high performance liquid chromatography in adult male mice from three different strains: 40 mice with genetically low (MGL) or high (MGH) blood magnesium levels, obtained by selective breeding and 20 outbred Swiss albino mice. Brain wet weight and noradrenaline levels were significantly higher in MGL than in MGH and Swiss mice. Few or no differences were found between MGH and Swiss mice. MGL and MGH animals had a similar mean body weight, were raised in identical conditions, and were fed with a normal diet, rich in magnesium. These results together with the higher urinary noradrenaline excretion previously observed in the MGL line, indicate that the mere selection for genetic traits inducing low blood magnesium levels entails an increased catecholamine production. This phenomenon most probably accounts for the higher sensitivity and/or reactivity of MGL animals to stress. The possible role of magnesium-controlling genetic factors in the regulation of brain growth is also suggested. PMID- 8369197 TI - Hypothesis: possible links between the respiratory distress syndrome of the premature neonate, the sudden infant death syndrome, and magnesium deficiency shock. AB - This hypothesis notes the similarities in the respiratory distress syndrome (RDS) of premature neonates, sudden infant death syndrome (SIDS) of postneonates, and the seizure-shock syndrome of acute magnesium (Mg) deficiency in stressed weanling animals, and suggests a common pathogenic link between the three. In each of these syndromes the lung is the major target organ, with haemorrhage, oedema, and microvascular congestion. It is suggested that platelet aggregation, leading to the transient release of mediators of shock, causes an acute, self limited arachidonic acid cascade. The result of the shock is early death or spontaneous recovery with a propensity for recurrence; premature neonates who have had RDS are at particularly high risk for SIDS. Cases linking RDS and SIDS are cited. PMID- 8369198 TI - Blood magnesium, potassium, sodium, calcium and cortisol in drug-free depressed patients. AB - Many biochemical variables, including plasma and erythrocyte magnesium, were simultaneously measured in drug-free depressed patients (n = 34), compared to healthy controls (n = 35). Higher plasma and erythrocyte magnesium concentrations were observed in patients than in controls (+12 per cent, P < 0.0001 and 14 per cent, P < 0.0001, respectively). In contrast, patients showed a lower plasma potassium level (-10 per cent; P < 0.007). Cortisol secretion was much higher in patients (+35 per cent; P < 0.02), particularly in females, showing overactivity of the hypothalamo-hypophyseo-adrenal axis in the patients. Except in a few cases, plasma sodium and calcium in patients did not differ from control values. Significant differences in magnesium and cortisol levels were observed between patients classified in diagnostic groups and by sex, whereas little variation in the other biochemical indices was noted. The increase in blood magnesaemia and its possible association with central hypocatecholaminergic deficiency in affective disorders are discussed. PMID- 8369199 TI - Potassium replacement associated with the development of tetany in a patient with hypomagnesaemia. AB - A case of hypomagnesaemia secondary to cisplatin therapy and diarrhoea had concomitant hypokalaemia. Increasing the serum potassium level from 2.8 to 3.4 mmol/litre by potassium supplementation induced tetany. Hypokalaemia in the face of hypomagnesaemia may have a membrane-stabilizing effect and preserve excitability. PMID- 8369200 TI - Magnesium content of human myometrium and placenta during various stages of gestation, and of different body fluids at term. AB - Pregnancy is marked by a state of hypomagnesaemia but not much is known about the effects of maternal magnesium deprivation on the fetus. The aim of this study was therefore to measure magnesium concentrations in human myometrial and placental tissues and in different body fluids during pregnancy and at term, using atomic absorption spectrophotometry. The magnesium concentration in umbilical cord blood was higher than in the maternal blood, supporting the existence of an active magnesium transport system. There was also a difference between the magnesium concentration in the amniotic fluid and that in the umbilical cord blood. The magnesium content of myometrium increased from the 32nd week of pregnancy, reaching its maximum level at the 37th week of gestation. Later there was significant decrease in magnesium level until the end of pregnancy. The magnesium content of placental tissue did not change up to the 30th week of pregnancy; however, it then decreased continuously during the last trimester. The significant improvement experienced in certain pathological conditions of pregnancy treatment with magnesium supports the existence of a magnesium deficit induced by pregnancy and the need for magnesium supplementation. PMID- 8369201 TI - Control of a cerebrospinal meningitis epidemic. PMID- 8369202 TI - Diarrhoeal Diseases Control Programme. Evaluation of training and performance. PMID- 8369203 TI - Measles in 1992. PMID- 8369204 TI - Lasers in dermatology. AB - Lasers have many applications in dermatology. Recent developments in laser technology have produced significant therapeutic advances in several areas. The introduction of pulsed tunable dye lasers has considerably improved the treatment of vascular lesions, particularly port wine stain malformations in children. A wider range of continuous-wave and quasi-continuous-wave lasers have also become available for treating vascular lesions, and their use in conjunction with automated delivery systems has improved results whilst reducing adverse effects. Increasing interest in treatment of pigmented lesions and tattoos has led to investigation of a range of high-power short-pulse lasers, and early results look very promising. However, further work is needed in all these areas to determine which lesions respond best to each laser system, and which treatment techniques are optimal. PMID- 8369205 TI - The effect of oral activated charcoal on the course of congenital erythropoietic porphyria. AB - The administration of oral activated charcoal to two patients with congenital erythropoietic porphyria has previously been reported to result in a marked reduction in plasma and urinary porphyrin concentrations and in one case, clinical remission. We describe an additional case in which the use of charcoal was associated with an apparent exacerbation of the biochemical activity of the disease following an initial period of remission. This result is unexpected, and currently unexplained. We conclude that charcoal therapy in porphyria may not be without risk, and should be used with caution. PMID- 8369206 TI - The effect of hormonal changes on cutaneous disease in lupus erythematosus. AB - The behaviour of cutaneous disease in systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE), under the influence of various hormonal states, was studied in 68 patients. In 28 pregnancies, cutaneous disease was essentially unchanged. In a total of 57 patients whose lupus erythematosus (LE) had been diagnosed prior to the menopause, 20% described a premenstrual cutaneous exacerbation. Only three patients had taken an oestrogen-containing contraceptive. The duration of oral contraceptive treatment before the onset of lupus varied: 1 month in a patient presenting with the acute malar rash of SLE, 2 months in a patient who presented with annular weals and later developed systemic features, and 12 months in a patient who developed generalized DLE. Thirty-three patients were menopausal at the time of the study; 4% had noticed a perimenopausal cutaneous flare. There was no deterioration in the skin of the five patients on hormone replacement therapy. PMID- 8369207 TI - The vellus hair follicle in acne: hair growth and sebum excretion. AB - In this study we investigated the activity of the vellus hair follicle in acne. Hair growth and sebum excretion in vellus hair follicles were measured on the forehead and back of men, and on the forehead, cheek, and back of women with acne. Hair growth was assessed by computerized image analysis (phototrichogram), and sebum excretion by computer analysis using Sebutape. In patients with acne, marked differences were revealed when results were compared with recent data from healthy persons. In particular, the mean growth rate of vellus hairs was higher, whereas the percentage of anagen hairs was lower, and the duration of the anagen phase shorter in patients with acne than in healthy individuals. Hair growth and sebum excretion depended significantly (P < 0.01) on the anatomical site (forehead 414 hairs/cm2, 0.053 mm/day, 34%; back 93 hairs/cm2, 0.16 mm/day, 21%). In addition, analysis of hair growth revealed significantly higher values in females than in males for (i) percentage of anagen hairs (P > 0.01), (ii) for vellus hair length (P < 0.05), and (iii) for the duration of the anagen phase (P < 0.01). The present study demonstrates that the activity of the vellus hair follicle is influenced by acne, and vice versa, and therefore its role in the aetiopathogenesis of acne should be reconsidered. PMID- 8369209 TI - PUVA treatment for alopecia areata--does it work? A retrospective review of 102 cases. AB - The results of PUVA treatment for severe alopecia areata (AA) were reviewed in 102 patients. Fifty-three per cent had greater than 90% regrowth of hair. Although these results appear to be encouraging, they differ little from what would be expected with no treatment. We consider that PUVA is not an effective treatment for AA. PMID- 8369208 TI - PUVA and cancer: a case-control study. AB - A detailed case-control study was carried out on 24 PUVA-treated patients with squamous cell cancer of the skin, and on an accurately matched control population of 96 PUVA-treated patients. Possible co-carcinogens, such as prior therapy with tar, ultraviolet-B, ionizing radiation, methotrexate and arsenic, were investigated. The only statistically significant association to emerge was that of prior therapy with methotrexate: relative risk 3.5; 95% confidence interval 1.2-9.9. Our data suggest that prior therapy with methotrexate might be a risk factor for skin cancer in PUVA-treated patients. PMID- 8369210 TI - Increased adherence to keratinocytes of peripheral blood mononuclear leucocytes of a patient with drug-induced erythema multiforme. AB - The pathogenetic mechanisms involved in the development of drug-induced erythema multiforme (EM) are still largely unknown. The observation that epidermal keratinocytes (KC) in EM express intercellular adhesion molecule-1 (ICAM-1) points to a putative role for T-cell/KC adhesion in the pathogenesis of EM. In this study, the binding of peripheral blood mononuclear leucocytes (PBML) from a patient with carbamazepine-induced EM and of normal control PBML to autologous and heterologous KC was investigated, using two different binding assays. Patient PBML obtained at the time of disease (t0) showed an increased binding to ICAM-1 positive heterologous KC, which could be inhibited completely by anti-LFA-1. Adhesion of patient PBML-t0 to autologous KC, and to carbamazepine-pretreated heterologous KC in sections of skin biopsies, was also increased, but was found to be only partially LFA-1-dependent. These findings support the view that PBML/KC adherence plays an important role in the pathogenesis of this drug induced EM. PMID- 8369211 TI - Dose-response testing with nickel sulphate using the TRUE test in nickel sensitive individuals. Multiple nickel sulphate patch-test reactions do not cause an 'angry back'. AB - The aim of this study was to employ the TRUE test assay to confirm the presence or absence of the 'angry back' phenomenon, i.e. that a strong positive patch-test reaction heightens adjacent patch-test response. In addition, we wished to establish the dose-response relationship for nickel sulphate patch tests among nickel-sensitive patients. Seventy-two nickel-sensitive patients, 36 in Odense and 36 in Stockholm, were tested with a 10-step nickel sulphate dilution series (TRUE test) and two placebo patches. The position of the patches was rotated, to provide a balanced spatial distribution of the different concentrations. Readings were performed blind. The results were analysed by means of polynomial multiple regression methods and a logistic dose-response model. Half the patients (38/72) had a threshold patch-test concentration for nickel sulphate in the range of 3 0.3 microgram/cm2. The 'angry back' phenomenon was not apparent in this study, as the spill-over effect was not statistically significant. Strong reactions to high concentrations of nickel sulphate did not enhance the response to adjacent lower concentrations of nickel sulphate. PMID- 8369212 TI - Dermatomyofibroma: additional observations on a distinctive cutaneous myofibroblastic tumour with emphasis on differential diagnosis. AB - Following the very recent description of a benign plaque-like myofibroblastic tumour of the skin, known as dermatomyofibroma, we present four further cases, emphasizing its clinical features and its histological differential diagnosis. Three patients were adult females and one was a boy. Two of the lesions arose on the anterior abdominal wall, one on the shoulder, and one on the neck. Clinically, there was often close resemblance to a keloid. Follow-up revealed no evidence of recurrence after simple excision. Histologically, these were non encapsulated but well-circumscribed, plaque-like lesions located in the reticular dermis, and composed of fascicles of monomorphic myofibroblasts, orientated parallel to the skin surface. Immunohistochemically, most of the tumour cells expressed alpha-smooth-muscle actin. The principal differential diagnosis is plaque-stage dermatofibrosarcoma protuberans. Other differential diagnoses include diffuse neurofibroma, dermatofibroma and other myofibroblastic skin tumours. PMID- 8369213 TI - High-dose topical calcipotriol in the treatment of extensive psoriasis vulgaris. AB - Ten patients with extensive plaque psoriasis were treated with calcipotriol ointment (50 micrograms/g) for 2 weeks (200 g for 1 week, followed by 300 g during the second week). Mean improvement in psoriasis area and severity index (PASI) was 71%. Mean 24 h urine calcium rose from 4.79 mmol/24 h to 7.27 mmol/24 h (P < 0.0001). Urine calcium returned towards baseline after stopping calcipotriol. Mean serum calcium also rose slightly, but significantly, from 2.26 mmol/l to 2.32 mmol/l (P < 0.005), and fell again in the washout phase. Individual serum calcium values remained within the normal range throughout the study. Topical calcipotriol is an effective, rapidly acting and safe in-patient treatment for extensive plaque psoriasis. PMID- 8369214 TI - Hydralazine predisposes to acute cutaneous vasculitis following urography with iopamidol. AB - We report a 60-year-old woman with renovascular hypertension who developed a severe cutaneous vasculitis 24 h after the injection of iopamidol during urography. A review of the literature suggests that her concomitant hydralazine therapy probably predisposed her to this reaction, as similar reactions have occurred in systemic lupus erythematosus, and hydralazine can induce a LE-like syndrome. We recommend that urography should be avoided in patients receiving hydralazine. PMID- 8369215 TI - Collodion baby dehydration: the danger of high transepidermal water loss. AB - We describe transepidermal water loss (TEWL) measurements in a collodion baby suffering from severe hypernatraemic dehydration and hypothermia, who required intravenous fluid therapy in a special incubator. The TEWL values 4 days after birth were abnormally high compared with normal infants of the same age. The TEWL measurements returned towards normal within the first month, in parallel with the improvement of both the skin signs and the electrolyte and fluid balance. PMID- 8369216 TI - An unusual case of transient papular mucinosis associated with carpal tunnel syndrome. AB - A 67-year-old man presented with discrete mucinous papules on the scalp and fingers, and bilateral carpal tunnel syndrome. Both features remitted spontaneously within several months. The acral distribution, and histopathological features, were in keeping with the recently described acral persistent papular mucinosis. Involvement of the scalp, however, has not previously been described, and transient mucin deposition is unusual. The history of bilateral carpal tunnel compression raises the possibility of extracutaneous involvement, not previously reported in this group of patients. PMID- 8369217 TI - Detection of latent variegate porphyria by fluorescence emission spectroscopy of plasma. AB - The plasma of patients with overt variegate porphyria contains porphyrin with a fluorescence emission maximum at about 626 nm, which is diagnostic for the condition. We have evaluated qualitative fluorescence emission scanning of saline diluted plasma as a method for the identification of asymptomatic carriers of the gene for variegate porphyria. Plasma from 36 unrelated patients with variegate porphyria, 136 of their asymptomatic first- and second-degree relatives aged 15 years or over, and 322 normal subjects was scanned. An emission maximum between 621 and 627 nm was observed in the 36 patients with variegate porphyria and 54 of their relatives, but not in any normal subject, nor in 56 patients with other types of porphyria. For the detection of asymptomatic adult carriers of the gene for variegate porphyria, fluorescence emission scanning of plasma appears to be 100% specific, with a sensitivity of 86% (95% confidence interval 71-98%). In contrast, the sensitivity of faecal porphyrin analysis as a test for adult gene carriers was 36%. These results suggest that fluorescence emission scanning of plasma should replace faecal porphyrin analysis as the test of first choice for this purpose. PMID- 8369218 TI - Vulvitis chronica plasmacellularis (Zoon's vulvitis). AB - Vulvitis chronica plasmacellularis (Zoon's vulvitis) is rare. We describe a case in whom all the typical features, as delineated by Zoon, are demonstrated. PMID- 8369219 TI - Diagnostic accuracy for basal cell papillomas. PMID- 8369220 TI - Cutaneous abscess: a rare complication of Streptobacillus moniliformis infection. PMID- 8369221 TI - Unusual onset of lupus erythematosus profundus. PMID- 8369222 TI - Tissue-specific regulatory elements of the Drosophila Gld gene. AB - Putative cis-acting regulatory elements immediately upstream of the Gld promoter were identified by comparative analysis of three Drosophila species. A 509 bp region containing these elements and the Gld promoter region was shown to confer tissue-specific regulation to a reporter gene similar to the pattern observed for Gld mRNA and protein. A dispersed repeat with a core motif of TTAGA was also capable of directing the expression of a reporter gene to several epidermally derived tissues in which GLD is normally expressed. These tissues include male and female somatic reproductive organs. The TTAGA elements and a palindromic element act antagonistically to block expression of reporter gene in some tissues. Previously reported mutations of the heat shock response element resulted in the creation of three TTAGA elements. This mutated hsp70 promoter directs expression of a reporter gene to many of the same tissues as does the Gld TTAGA elements. We have found TTAGA elements near the promoter of two other genes which show an identical expression pattern in the male ejaculatory duct as Gld and the mutant hsp70. PMID- 8369223 TI - Changes in protooncogene expression correlated with general and sex-specific differentiation in murine primordial germ cells. AB - Primordial germ cells (PGCs) of the mouse undergo key developmental transitions during embryonic days 12-15. On day 12 they complete migration into the gonads. They cease mitotic proliferation on day 13 and subsequently enter sex-specific pathways of development. The molecular mechanisms controlling these transitions are poorly understood, yet they are crucial to production of normal gametes later in life. We have used the polymerase chain reaction (PCR) to directly compare levels of expression of several protooncogenes proposed to be involved in control of cell proliferation and differentiation in proliferating and differentiating PCGs of both sexes over a 4 day time course. We report here that mRNA levels for nuclear protooncogenes c-myc, c-fos, and c-jun increase dramatically in both sexes from little or no detectable expression on day 12 to high expression on days 13-15. We observe c-kit message on day 12 in combined PGCs of both sexes, in female but not male PGCs on day 13, and in both sexes on day 14, c-kit mRNA is undetectable on day 15 in either sex, c-mos is not expressed at detectable levels on day 12 in either sex, but increases gradually in female PGCs to very high levels on day 15. In male PGCs, c-mos is expressed at high levels on days 13-15. Our results are consistent with a role for protooncogenes c-myc, c-fos and c-jun in mediating the initial differentiation of PGCs of both sexes that occurs upon colonization of the gonad. Because c-kit and c-mos are expressed differentially in male and female day 13-15 germ cells, they may play roles in initiating or mediating progress along the sex-specific pathways of development that PGCs embark upon at this time. PMID- 8369224 TI - Cloning and developmental expression of Grg, a mouse gene related to the groucho transcript of the Drosophila Enhancer of split complex. AB - Genes of the Enhancer of split complex are involved in neural-epidermal cell fate decisions during early embryogenesis in Drosophila. One of these genes, the product of the Enhancer of split m9/10 or groucho transcript, encodes a ubiquitous nuclear protein with homology at the carboxy-terminus to G-protein beta-subunits. Here we describe the cloning and RNA expression analysis of a mouse gene, designated Grg, that is homologous to just the amino-terminal region of the groucho product. Grg encodes a 197 amino acid protein that shares 53% amino acid identity with the corresponding region of the product of the Drosophila groucho gene. However, the mouse Grg protein does not contain the region homologous to G-protein beta-subunits. An analysis by in situ hybridization of the spatial and temporal localization of Grg RNA expression revealed that, while the initial pattern of Grg expression was quite restricted, by midgestation Grg RNA was ubiquitously expressed in the developing embryo. Widespread Grg RNA expression was maintained in adult mice. The implications of these results for the existence of separable functional domains of the Drosophila groucho product, and possible roles of the Grg gene during mouse development, are discussed. PMID- 8369225 TI - Contrasting distributions of patched and hedgehog proteins in the Drosophila embryo. AB - The segment polarity genes patched (ptc) and hedgehog (hh) are thought to encode a receptor and signal molecule respectively, components of a signal transduction pathway that regulates the transcription of the wingless gene in the Drosophila embryo. Here we describe the production of antibodies specific for the products of these two genes and the patterns of protein distribution that they reveal in the developing embryo. The results are consistent with the hh protein being secreted by cells in which it is expressed and support a role for ptc in the reception of the putative hh encoded signal. PMID- 8369226 TI - Egg ligation alters the Bcd protein gradient and segmentation gene expression in embryos of Drosophila. AB - A concentration gradient of the anterior morphogen Bicoid (Bcd) plays a key role in the specification of cell fates in the early Drosophila embryo. We found that introduction of a membrane barrier across the embryo results in increased levels of Bcd protein on the anterior side of the barrier and decreased levels on the posterior side, consistent with a blockage in the postulated anterior-to posterior translocation of Bcd protein. The expression patterns of downstream segmentation genes were in large part consistent with their regulation by the Bcd morphogen. However, some aspects of the patterns did not correlate with the altered Bcd distribution, suggesting that other morphogens also regulate the anteroposterior pattern. Our results suggest that axial translocation of morphogens is critical for establishing a well-proportioned body plan. PMID- 8369227 TI - Prenatal cerebral development in individuals at genetic risk for psychosis: head size at birth in offspring of women with schizophrenia. AB - Previous investigation has shown preschizophrenics to have disproportionately small head circumferences (HC) (in relation to body length) at birth, providing further evidence of disturbed prenatal cerebral development among preschizophrenics. This reduced HC at birth appeared to have resulted from some factor(s) other than genetic risk for schizophrenia, as reduced HC was significantly related to an absence of family history of psychosis. A re-test of the finding that genetic risk for schizophrenia is not associated with reduced HC at birth was performed in the current high-risk study, which compared HC: body length ratios at birth in 31 offspring born to women with a history of schizophrenia vs. 38 demographically comparable control offspring. The genetically high-risk offspring were highly similar to control offspring of HC: body length ratios, supporting the previous findings that disturbed prenatal cerebral development, as measured by disproportionately small HC, is not a function of genetic risk for schizophrenia. PMID- 8369228 TI - Ultrastructural features of biopsied temporopolar cortex (area 38) in a case of schizophrenia. AB - An electron microscopic study of tissue from area 38 of the temporopolar cortex obtained at surgery from a schizophrenic patient has established that, although the ultrastructure of this area was in general similar to that found in normal human cerebral cortex, the neuropil contained many unusual asymmetrical synapses. Their synaptic vesicles were clumped, often away from the synaptic thickenings, and the thickenings themselves were short, compared to the total length of apposed pre- and postsynaptic membranes. Some preterminals were unusual in that they were myelinated. The affected terminals were always of the asymmetrical variety, and therefore probably excitatory. Glutamate is likely to be the transmitter at, at least, some of these synapses. The clumped, but numerous, synaptic vesicles, together with short synaptic active zones, is consistent with previous observations of normal glutamate levels in schizophrenic brain, but reduced numbers of glutamate receptors in some cortical areas. PMID- 8369229 TI - The use of clozapine in treatment-refractory schizophrenia. AB - The effects of clozapine on positive and negative symptoms were studied in 103 patients with treatment-refractory schizophrenia. The evaluation of symptom profile was made before and after clozapine treatment. Overt psychopathology did not vary significantly before clozapine treatment. Significant decreases in positive and negative symptoms were noted by the third month on clozapine. No further significant progress could be observed after 6 months of treatment. No fatal cases were observed, although two patients developed agranulocytosis during clozapine treatment. PMID- 8369230 TI - Haloperidol response and plasma catecholamines and their metabolites. AB - Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug. PMID- 8369231 TI - The clinical relevance of an auditory attention task (PAT) in a longitudinal study of chronic schizophrenia, with placebo substitution for chlorpromazine. AB - A new auditory attention task (PAT) is described. The test comprises four different subtest combinations (diotic/dichotic, slow/fast) each of 5 min duration. Omission and commission errors are combined by an index of errors (IE). The PAT was given fortnightly to 20 chronic schizophrenic inpatients for more than one year. Independent psychiatrists rated the patients according to the Brief Psychiatric Rating Scale and a Global Rating Scale. All measures yielded significant test-retest reliabilities. The patients were stabilized on individualized doses of chlorpromazine (CPZ) and randomized to two groups. Placebo was substituted for CPZ during 10 weeks, according to a double-blind cross-over design. Significant deterioration under placebo was detected by all three methods, but the PAT was the most sensitive to change. The PAT mean score (M IE) was correlated with both rating scales. Unlike the rating scales, it also correctly ordered the twenty patients along a dimension which measured the severity of illness and 'predicted' hospital discharge. PMID- 8369232 TI - Effects of placebo, orphenadrine, and rising doses of chlorpromazine, on PAT performance in chronic schizophrenia. A two year longitudinal study. AB - An earlier study (Study 1: 14 months duration) showed that the PAT (an auditory attention task) is sensitive to changes of clinical state in chronic schizophrenia and is able to predict hospital discharge. The newly presented study (Study 2: 12 months duration) investigated the effects of increasing the dose of chlorpromazine (CPZ) stepwise (double-blind) to between 900 mg and 1800 mg per day, in 10 of the original 20 patients. Measurements were made fortnightly throughout both studies and the data were depicted continuously for each patient. Study 2 showed that a 300% increase of CPZ dose neither improved nor impaired PAT performance. Also, the addition of orphenadrine 300 mg per day had no significant effect on performance. Four types of relapse were detected. The first was induced by placebo substitution for CPZ and recovered when the drug was reinstated. The remaining types of relapse were all resistant to CPZ and comprised: a long-period pattern with a spontaneous reversal; unremitting deterioration; and a short period pattern of labile relapse and recovery. PMID- 8369233 TI - Factor analysis of schizophrenic symptoms and comparison of different rating scales. AB - This study examines the factor structure of persistent schizophrenic symptoms and compares factors derived from different rating scales. Forty stable chronic schizophrenic patients were assessed for positive and negative symptoms. In factor analysis, 3 factors could be detected: a negative factor which correlated with low drug dose and increased involuntary movements, a thought disturbance/paranoid factor which correlated negatively with extrapyramidal side effects and a delusion/hallucination factor which correlated negatively with involuntary movements. These findings support the existence of a negative factor but only partly the trichotomous division of schizophrenic symptoms. Positive symptom organisation is heterogeneous but thought disorder marks one clear dimension and non-paranoid delusions and hallucinations may mark another. The type of scale used has very significant effects on the findings. PMID- 8369235 TI - Cognitive functioning and anhedonia in subjects at risk for schizophrenia. AB - This study investigated the performance of individuals with familiar loading of schizophrenia (healthy siblings of schizophrenic inpatients) on three neuropsychological tasks assumed to require frontal lobe functions: Trail Making Test (TMT), verbal fluency and Wisconsin Card Sorting Test (WCST). Healthy siblings of schizophrenics differed in performance from healthy controls not only on the WCST, but also on the Trail Making Test and the verbal fluency task. Furthermore, scores of physical anhedonia, assessed in a self-report rating scale (Chapman et al., 1976) were also significantly higher in the high risk group than in the control sample. However, healthy siblings of schizophrenics did not differ from controls with regard to experiences of perceptual aberrations, measured by the same method (Chapman et al., 1978). Neuropsychological performance and elevated anhedonia scores in the high risk group were interpreted under the conceptual framework of vulnerability markers: they were supposed to represent a trait shared by family members of schizophrenic probands. Amongst the neuropsychological tests, there were significant correlations between the physical anhedonia score and WCST and Trail Making test performance in the group of healthy siblings of schizophrenics, but not in the control group. PMID- 8369234 TI - Puberty and the onset of psychosis. AB - According to the neurodevelopmental hypothesis of schizophrenia, maturational events in the brain at puberty interact with congenital defects to produce psychotic symptoms. As girls reach puberty at a younger age than boys, we predicted that (i) females would show earlier onset of psychotic illness arising around puberty, and (ii) onset of psychosis in females would be related to menarche. Analysis of epidemiological data regarding admission to psychiatric units in (a) England over the period 1973-1986, (b) France over the period 1975 1980, as well as examination of 97 psychotic adolescents referred to an adolescent unit over a 14 year period, supported both these propositions. PMID- 8369236 TI - Memory functioning in chronic and non-chronic schizophrenics, affectively disturbed patients and normal controls. AB - Memory impairment has been reported among schizophrenics in several studies. There are a number of uncertainties in interpreting such deficits. The present study examined short- and long-term verbal memory in schizophrenic patients (n = 30), affectively distributed patients (n = 18) and normal controls (n = 18). Schizophrenics showed a significant decrease in memory test performance, compared with both normal controls and other psychiatric patients. Chronic schizophrenics seem to be characterized by qualitatively different memory functioning compared with non-chronic subjects. In a free recall task chronic subjects showed significantly decreased performance for the initial (primacy) and final (recency) items. Memory functioning was not correlated with performance on the Wisconsin Card Sorting Test. This could indicate a selective cognitive dysfunction of an amnesic nature in chronic schizophrenics. PMID- 8369237 TI - Stimulation of murine intestinal intraepithelial lymphocytes by the bacterial superantigen staphylococcal enterotoxin B. AB - To gain insight into the specificity and function of intestinal intraepithelial lymphocytes (IEL), we have examined their response to staphylococcal enterotoxin B (SEB), a significant cause of food poisoning and a potent T cell mitogen. IEL include two populations of TCR alpha beta+ T cells. One of these resembles the T cells found in the Peyer's patch and is thymus dependent. The other subset is characterized by both TCR alpha beta and gamma delta+ IEL bearing a unique form of the CD8 molecule, expressed as an alpha alpha homodimer. CD8 alpha+ beta- IEL are thymus independent and appear to mature extrathymically in the gut epithelium. Two-color flow cytometric analysis showed that in vitro stimulation of IEL with SEB resulted in the expansion of the thymus dependent but not the thymus independent IEL; the CD8 alpha+ beta- IEL were functionally non-responsive to stimulation with SEB. 'Forbidden' self-superantigen reactive T cells present among IEL were also non-responsive to stimulation with SEB. The presence or absence of class II MHC molecules does not appear to play a role in the non responsiveness to SEB, since CD8 alpha+ beta- IEL from class II deficient mice also failed to respond to stimulation with SEB. Depletion of CD8 beta+ and CD4+ T cells from total IEL decreased IL-2 production by IEL in response to cross linking with anti-CD3, suggesting that the non-responsiveness of CD8 alpha+ beta- IEL extends to antigens other than SEB. PMID- 8369238 TI - Functional inactivation of the CD3 zeta chain in a T cell hybridoma by in vitro gene targeting. AB - Specific inactivation of the CD3 zeta or CD3 eta gene was introduced into a murine T cell hybridoma cell line by homologous recombination to elucidate the role of the CD3 zeta chain in the assembly of and signal transduction through the TCR complex. Since CD3 zeta and CD3 eta are alternatively spliced forms from a common gene with the only difference occurring in the last exon, we constructed targeting vectors by introducing a neomycin phosphotransferase gene into the CD3 zeta- or CD3 eta-specific exon to selectively inactivate zeta or eta. Subsequently, clones bearing a mutated allele were established. In spite of the disruption of only a single allele of the CD3 zeta gene in the CD3 zeta-targeted clone, most of the authentic zeta transcripts and zeta proteins disappeared from the cells, resulting in an extreme decrease in cell surface expression of the TCR complex. Consequently, these cells exhibited no antigen response. These defects were compensated by transfecting the CD3 eta gene. These results confirm previous studies on a somatic mutant showing that CD3 zeta has crucial roles in antigen recognition by and signaling through, as well as the expression of, the TCR-CD3 complex. Our results suggest that there is a major transcriptionally active allele for the expression of these genes in this cell line which seems to be susceptible to homologous recombination. In vitro gene targeting, therefore, provides a powerful approach for studying the roles of intracellular molecules. PMID- 8369239 TI - Emergency contraception: time for de-regulation? PMID- 8369240 TI - Male infertility. PMID- 8369241 TI - Endometriosis: still an enigma. PMID- 8369242 TI - A paramedic based emergency domiciliary obstetric service: the South Glamorgan experience. AB - OBJECTIVE: To assess the potential benefits of using extended trained ambulance personnel (paramedics) as primary responders for domiciliary obstetric and gynecological emergencies. DESIGN: An observational study of performance and analysis of operational data in a newly established service. SETTING: A mixed urban and rural population served by South Glamorgan Health Authority. MAIN OUTCOME MEASURES: Work load, response times, management and transfer of patients, efficiency of communications and appropriateness of training. RESULTS: There was an initial increase in requests above that when a hospital-based service operated. Targets for response times were met. The mean response time for providing appropriate skilled help was halved compared with the previous arrangements and a safe and efficient service was provided. Prompt transport and advance notice and preparation for reception in the delivery unit contributed to optimal management. Medical staff depletion in the delivery unit was minimised. CONCLUSION: An Emergency Domiciliary Obstetric Service based on primary response by specially trained ambulance service paramedics can beneficially replace traditional hospital-based Obstetric Flying Squads. PMID- 8369243 TI - Phenytoin prophylaxis in severe pre-eclampsia and eclampsia. AB - OBJECTIVE: To determine plasma phenytoin levels and seizure outcome in women given phenytoin for seizure prophylaxis in severe pre-eclampsia and eclampsia. DESIGN: Prospective observational study comparing two phenytoin loading regimens. SETTING: Two UK teaching hospitals. SUBJECTS: Sixty-seven consecutive women with severe pre-eclampsia and five with eclampsia. INTERVENTIONS: The first 29 women were given a 15 mg/kg intravenous loading dose of phenytoin. The next 43 received 17.5 mg/kg. All were given 500 mg phenytoin 12 h after completion of the loading dose and then 250 mg every 12 h for four doses. MAIN OUTCOME MEASURES: Total plasma phenytoin levels at 30 min, 6 h and 12 h after loading dose, 6 h after first maintenance dose and on days 2 and 3 of maintenance therapy; eclamptic seizures after starting phenytoin. RESULTS: Mean plasma phenytoin levels were higher at 30 min and 6 h after the 17.5 mg/kg loading dose. Nine of 29 (31%) phenytoin levels 30 min after the loading dose were above the therapeutic range in the 15 mg/kg group compared with 26/38 (68%) in the 17.5 mg/kg group (P < 0.01). Six of 27 (22%) phenytoin levels 12 h after the loading dose were subtherapeutic in the 15 mg/kg group compared with 2/38 (5%) in the 17.5 mg/kg group (P < 0.05). Three women, two in the 17.5 mg/kg group, developed seizures after starting phenytoin. All three had plasma levels within the therapeutic range. CONCLUSIONS: Compared with a loading dose of 17.5 mg/kg, loading with 15 mg/kg phenytoin was associated with a lower incidence of high plasma levels at 30 min but a higher incidence of subtherapeutic levels at 12 h. Seizures occur in 2 to 3% of pre-eclamptics despite apparently therapeutic phenytoin levels. PMID- 8369244 TI - The effect of anxiety and depression during pregnancy on obstetric complications. AB - OBJECTIVE: To investigate the effects of anxiety and depression during pregnancy on obstetric complications using the data collected from the St George's Birthweight Study. DESIGN: Prospective population study. SETTING: District general hospital in inner London. SUBJECTS: A consecutive series of 1860 white women booking for delivery were approached. Of these, 136 refused and 209 failed to complete the study for other reasons, leaving a sample of 1515. MAIN OUTCOME MEASURE: Data were obtained by research interviewers at booking, 17, 28, and 36 weeks gestation and from the structured antenatal and obstetric record. The predictor variables were the anxiety and depression scores measured using the General Health Questionnaire. The outcome variables were five obstetric complications: preterm delivery; nonspontaneous onset of labour; major analgesia in the first and second stages of labour; and nonspontaneous vaginal deliveries. The possible confounding effects of 35 socio-economic, psychological and personal variables were investigated using logistic regression. RESULTS: The factors that had the strongest relation with the outcomes were parity and maternal age. Depression during pregnancy was unrelated to the obstetric complications. Anxiety was weakly related to analgesia/anaesthesia in the second stage of labour (P = 0.04). However, anxiety accounted for only 0.1% of the variance in use of major analgesia/anaesthesia. The most effective model, that for analgesia/anaesthesia in the first stage of labour, accounted for only 7.3% of the variance. CONCLUSIONS: In the general population of pregnant women, anxiety and depression during pregnancy, while undesirable in themselves, are of little importance in the evolution of obstetric complications. PMID- 8369245 TI - Cervical contractions: the response of the cervix to oxytocic stimulation in the latent phase of labour. AB - OBJECTIVE: To assess the cervical response to myometrial activity in early labour. DESIGN: Prospective observational study. SUBJECTS: Women requiring oxytocin stimulation in induced and spontaneous labours. SETTING: A teaching hospital in Birmingham. MAIN OUTCOME MEASURES: Simultaneous comparison of the cervical response to myometrial contractions was made on a cycle by cycle basis to deduce the properties of the cervix in early labour. RESULTS: Sixty-seven patients have been monitored, of whom 63 had satisfactory cervimetry data. Thirty (47.6%) women exhibited cervical contractions in response to myometrial activity. This response was only observed at dilatations up to 4 cm. The change in behaviour coincides with the transition from latent to active phases of dilatation. The length of the latent phase of labour was significantly longer in those women who exhibited cervical contractions (P < 0.001), although the active phase was similar in the two groups (P > 0.1). The group without cervical contractions exhibited a greater degree of effacement (P < 0.05) and tended to have more dilated cervices (P < 0.01) than those who showed cervical contractions. CONCLUSIONS: It is possible for the cervix to contract in early labour. This response may be the result of incomplete preparation of the cervix for the process of dilatation, and is seen during what is recognised as the latent phase in those women in whom the cervix is unaffected and undilated. These properties of the cervix may explain the poor results obtained from oxytocin stimulation of labour in the latent phase. PMID- 8369246 TI - Intravaginal misoprostol as a cervical ripening agent. AB - OBJECTIVE: To determine if misoprostol (exogenous prostaglandin E1 PGE1) used vaginally was of value in improving the Bishop score, leading to an early safe vaginal delivery in women in whom the cervix is unripe and delivery is indicated. DESIGN: A double-blind clinical trial. SETTING: Antenatal and labour wards of the University Hospital of the West Indies, Jamaica. SUBJECTS: Forty-five women in the third trimester with various obstetric indications for induction of labour and with no contra-indications to prostaglandins. INTERVENTIONS: The women were randomly assigned to receive treatment or a placebo. The treated group had 100 micrograms misoprostol inserted vaginally while the placebo was similarly inserted. MAIN OUTCOME MEASURES: Efficacy of the misoprostol was measured by the increase in the Bishop score 12 h after giving the treatment, the time between insertion and delivery, the need for oxytocin, and the outcome of the pregnancy. RESULTS: The prostaglandin was superior to the placebo in ripening the cervix and inducing labour. The change in Bishop score was 5.3 in the misoprostol group compared with 1.5 in the placebo group (P < 0.001). The mean time from insertion to delivery was 15.6 h in the former while it was 43.2 h in the placebo group (P < or = 0.001). The need for oxytocin was also significantly less in the women receiving the prostaglandin compared with those who received the placebo (29% vs 62%, P < 0.02). There was no difference in the two groups in the delivery outcome in terms of complications, Apgar scores and mode of delivery. CONCLUSIONS: Intravaginal misoprostol is an effective and cheap method of inducing labour in the third trimester. PMID- 8369247 TI - Are the WHO (1980) criteria for the 75 g oral glucose tolerance test appropriate for pregnant women? AB - OBJECTIVE: To determine the normal response to a 75 g glucose challenge in the context of an oral glucose tolerance test in the third trimester of pregnancy. DESIGN: Prospective observational study. SETTING: Antenatal clinic, Kandang Kerbau Hospital, Singapore. SUBJECTS: Sixty-four normal pregnant women with a low risk for diabetes. INTERVENTIONS: Glucose (75 g) challenge following an overnight fast after 28 weeks of gestation. MAIN OUTCOME MEASURE: Venous plasma glucose levels taken before and 2 h after the glucose challenge. RESULTS: Upper limits of normality were found to be fasting glucose 4.9 mmol/l and 2 h glucose 9.2 mmol/l. CONCLUSION: The WHO (1980) criteria should not be used in pregnancy. PMID- 8369248 TI - A nonpenetrating fetal scalp electrode. AB - OBJECTIVE: To develop a nonpenetrating scalp electrode for intrapartum fetal monitoring. DESIGN: Preliminary observational evaluation of the device. SETTING: An urban academic hospital in Johannesburg, South Africa. SUBJECTS: Fifteen women in labour. INTERVENTION: Application of the electrode for intrapartum monitoring. OUTCOME MEASURES: Quality of tracings, duration of application, disconnection of the electrode, marking of the scalp. RESULTS: Application was successful in 13 of 15 women, and high quality tracings obtained in 12. CONCLUSIONS: The design of scalp electrode tested is effective and produces high quality tracings in most cases. PMID- 8369249 TI - Prediction of fetal acidaemia in intrauterine growth retardation: comparison of quantified fetal activity with biophysical profile score. AB - OBJECTIVE: To study the relation between quantified fetal movements and fetal activity assessed by the biophysical profile score and the pH in umbilical arterial blood at elective caesarean section. DESIGN: Fetal activity was assessed within 24 h prior to caesarean section for decelerative fetal heart rate patterns both by quantification (% of time spent moving) and by applying the biophysical profile score (BPS) criteria. SETTING: Department of Obstetrics, University Hospital. SUBJECTS: Nineteen growth retarded fetuses. MAIN OUTCOME MEASURES: Fetal generalised movements (FGM%), fetal breathing movements (FBM%), total fetal activity (TFA% = FGM% + FBM%); FGM, FBM and tone as assessed according the biophysical profile score (BPS); umbilical arterial pH. RESULTS: In all 11 acidaemic fetuses (pH < 7.20) TFA% was below the 10th centile for normal fetuses; nine had decreased FGM% and eight decreased FBM%. Absence of FGM or tone according to the biophysical profile score was only seen in two acidaemic fetuses. CONCLUSION: TFA% < 11.7% was a better predictor of acidaemia at birth than either reduced FGM%, FBM%, or absence of FGM, FBM and tone as defined in the biophysical profile score. The two methods of assessing FBM were identical in predicting acidaemia, suggesting that in presence of acidaemia the decrease of FBM may be an all-or-none phenomenon. Furthermore, the data indicate that reduction in body movements may precede reduction in breathing movements. PMID- 8369250 TI - Invasive carcinoma of the cervix following local destructive treatment for cervical intraepithelial neoplasia. AB - OBJECTIVE: To investigate the occurrence of invasive carcinomas following local destructive treatment for cervical intraepithelial neoplasia (CIN) and to evaluate the factors responsible. DESIGN: A multicentre retrospective study. SUBJECTS: Forty-nine women registered with the British Society for Colposcopy and Cervical Pathology from 24 centres throughout Great Britain between 1985 and 1992, who had been treated by local destructive methods for CIN and who subsequently developed invasive carcinoma of the cervix. RESULTS: Of the 49 women whose details were submitted, 42 had squamous cell carcinoma, six adenosquamous carcinoma and one adenocarcinoma. Eight had microinvasive carcinomas (Stage Ia) at the time of diagnosis, 24 had Stage Ib tumours and eight Stages II to IV. Thirteen women have died. Thirty-five women had been treated by laser vaporization, ten by cold coagulator, two by diathermy and two by cryosurgery. In 19 women (39%) the diagnosis of invasive carcinoma was made on the first follow up visit or within one year of treatment. Five patients did not present with invasive disease until more than five years after treatment. CONCLUSIONS: The data presented suggest that many, but not all, of the invasive carcinomas presenting after local destructive treatment for CIN resulted from failure to recognise early invasive disease at the time of the initial assessment. The importance of thorough evaluation before undertaking these forms of treatment is emphasised. The use of excisional procedures should further reduce the small risk of invasive carcinoma developing after treatment for CIN. PMID- 8369251 TI - The Royal College of Obstetricians and Gynaecologists micro-invasive carcinoma of the cervix study: preliminary results. AB - OBJECTIVES: To determine how micro-invasive carcinoma of the cervix is diagnosed and treated in the United Kingdom. To record the frequency of the various pathological features which comprise the histological diagnosis of micro invasion, and to assess their relevance to outcome. DESIGN: Prospective observational study. SETTING: Hospitals throughout the United Kingdom. SUBJECTS: Two hundred and eighty-six cases were submitted for entry into the study. Following independent review of the histological material 116 cases were excluded: 41 were not accompanied by histological slides for review, 55 had no evidence of invasive disease, 17 had invasive disease greater than FIGO Stage 1a, and three were adenocarcinomas. The remaining 170 cases were registered for the study but follow up was incomplete in 18. This report concerns the 152 women with complete follow up to 1991. RESULTS: The age of the 152 women ranged from 22 to 65 years (median 36 years). In 116 women (76%) the diagnosis was made by cone biopsy (cold knife, loop diathermy, or laser) or wedge biopsy, in 9 women (6%) the diagnosis was made by hysterectomy, and in 27 women (18%) punch biopsy suggested an invasive lesion and subsequent excisional treatment (including radical hysterectomy with node dissection in three) demonstrated micro-invasion. The depth of invasion was up to 3 mm in 142 women (93%) and 3.1 to 5 mm in 10 women (7%). Capillary-like space involvement was present in 12 women (8%). Treatment methods used were local cervical surgery in 79 women (52%), simple hysterectomy in 63 (41%), and radical hysterectomy in 10 (7%). There was only one known recurrence and death due to cervical carcinoma. CONCLUSION: There is no uniformity in the management of micro-invasive carcinoma of the cervix. The frequency of recurrence, lymph metastases, and death is low. Nonradical surgery appears to give satisfactory results. PMID- 8369252 TI - Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension. AB - OBJECTIVE: To assess whether asymptomatic abnormalities, including thyroid auto antibodies, were associated with an abnormal miscarriage rate or a poor obstetric outcome. DESIGN: Prospective study of thyroid auto-antibodies and thyroid function in an unselected obstetric population. SETTING: Saint-Pierrie Hospital, Brussels, Belgium. SUBJECTS: Seven hundred and thirty consecutive pregnant women attending the antenatal clinic. MAIN OUTCOME MEASURES: Miscarriage and pregnancy induced hypertension. RESULTS: Elevated antithyroperoxidase (TPO-Ab) and antithyroglobulin (TG-Ab) antibody titres are associated with an increased miscarriage rate. Also, asymptomatic thyroid abnormalities, mainly abnormal echo structure but not antithyroid antibodies, are associated with pregnancy induced hypertension. CONCLUSION: The presence of thyroid auto-antibodies during pregnancy constitutes a marker of increased risk of miscarriage and poor obstetric prognosis. PMID- 8369253 TI - Erythrocyte sodium lithium countertransport in normal and hypertensive pregnancy: relation to haemodynamic changes. AB - OBJECTIVE: To establish the changes in erythrocyte sodium lithium countertransport (SLC) with advancing normal pregnancy and to determine if these changes were different in pregnancy induced hypertension (PIH). The changes in both groups were assessed in relation to haemodynamic changes. DESIGN: SLC, mean arterial pressure (MAP), cardiac output (CO) and total peripheral vascular resistance (TPVR) were determined serially during normal pregnancy and cross sectionally in PIH. Women were studied again 20 weeks after delivery where possible. SETTING: Routine antenatal clinic and antenatal ward of a regional reference centre. SUBJECTS: Fifty-one normal primigravid women were studied serially and 41 primigravid women with PIH were studied at time of diagnosis. RESULTS: During normal pregnancy SLC (mmol Li/h/l cells) increased from a nonpregnant value of 0.24 +/- 0.02 (mean +/- SEM) to 0.32 +/- 0.02 at 14 weeks, and 0.37 +/- 0.02 at 20 weeks gestation. This was maintained until 38 weeks (0.40 +/- 0.02). The increase until 20 weeks occurred at the time of greatest change in CO (5.10 +/- 0.18 to 6.79 +/- 0.20 l/min) and TPVR (1327 +/- 58 to 969 +/- 33 dyn/s/cm-5). The decrease in TPVR with a rise in SLC is opposite to the relation reported in essential hypertension so that a functional relation is unlikely. However, the changes within pregnancy were positively correlated (r = 0.43, P < 0.01). In hypertensive pregnancies TPVR was elevated compared with normotensive pregnancies (1543 +/- 100 vs 1090 +/- 37) but the SLC was not different from that found in normotensive pregnancies (0.43 +/- 0.02 vs 0.40 +/- 0.02). CONCLUSIONS: The changes in SLC activity suggest dynamic effects on erythrocyte membrane function during pregnancy. However, no differences could be found between normal and hypertensive pregnancy and SLC is unlikely to be of value as a marker of hypertensive risk during pregnancy. PMID- 8369254 TI - Alterations in erythrocyte chloride content accompanying the changes in erythrocyte hydration and potassium content in normal human pregnancy: a comparison with pregnancy induced hypertension. AB - OBJECTIVES: To determine whether the change in erythrocyte potassium content in normal human pregnancy is accompanied by a similar change in erythrocyte chloride content. To assess erythrocyte hydration and potassium and chloride content in pregnancies complicated by proteinuric pregnancy induced hypertension. DESIGN: A serial study during and after normal pregnancy. A comparative study during and after pregnancies complicated by proteinuric pregnancy induced hypertension (PIH). Erythrocyte hydration, total osmoles, potassium and chloride and plasma osmolality were determined. SETTING: University teaching hospital, UK. SUBJECTS: Twenty-eight women studied at 14, 28 and 36 weeks of normal pregnancy and ten women with PIH studied during the third trimester of pregnancy. All women were reinvestigated 20 weeks after delivery. RESULTS: The fall of erythrocyte potassium early in normal pregnancy (277.4 vs 265.2 mmol/kg; P < 0.02) and its rise between 28 and 36 weeks (272.3 vs 288.0 mmol/kg; P < 0.005) were accompanied by similar changes in erythrocyte chloride content (151.9 vs 131.1 mmol/kg; P < 0.001 and 129.4 vs 141.3 mmol/kg; P < 0.001, respectively). Plasma osmolality in PIH was raised above that normal in pregnancy (287.2 vs 283.0 mosm/kg; P < 0.005). In PIH, compared to normal pregnancy, erythrocyte hydration (2.00 vs 1.89 l/kg dry weight cells), total osmoles (573.0 vs 534.2 mosm/kg), potassium (303.0 vs 288.0 mmol/kg) and chloride (154.9 vs 141.3 mmol/kg) were greater. CONCLUSIONS: These findings further support the hypothesis that changes in plasma osmolality in pregnancy are secondary to alterations in cell osmoles and serve to limit changes in cell hydration. Erythrocyte composition and plasma osmolality are altered in PIH. PMID- 8369255 TI - Whole blood platelet aggregation in moderate and severe pre-eclampsia. AB - OBJECTIVE: To compare whole blood platelet aggregation in moderate and severe pre eclampsia with normal pregnancy. DESIGN: Whole blood platelet aggregation in response to collagen, ADP, PAF, adrenalin and arachidonic acid was measured in the pre-eclampsia group at 36 weeks gestation and at 1, 24 and 48 h and at five days and six weeks post delivery. The normal pregnancy group were studied serially at 12, 20, 28, 32, and 36 weeks gestation and at 1, 24, 48 h and six weeks post delivery. SETTING: Trinity College Medical School, St James's Hospital, Dublin. SUBJECTS: Thirty women with diagnosed pre-eclampsia were recruited for the study. Fifteen of these women had severe pre-eclampsia and the remaining 15 had moderate disease. The pre-eclampsia group were compared with 20 healthy primigravid women with uncomplicated pregnancies and deliveries. RESULTS: In women with severe pre-eclampsia, platelet aggregation in response to collagen, ADP, adrenalin and arachidonic acid was significantly lower at 36 weeks gestation compared with normal pregnancy. Lower levels of collagen induced aggregation were also found at 1 h post delivery when compared with normal pregnancy. Women with moderate pre-eclampsia showed a decreased response to aggregating agents at 36 weeks gestation but this was not significant. ADP, collagen and PAF induced aggregation was higher in women with moderate pre-eclampsia at 36 weeks gestation and during the early puerperium compared with severe pre-eclampsia. CONCLUSIONS: The clinical signs of pre-eclampsia are accompanied by a reduction in platelet responsiveness, the extent of which is related to the severity of the disease. This suggests that an abnormal platelet activation occurs early in pregnancies destined to be complicated by pre-eclampsia. This activation may be involved in the pathogenesis of pre-eclampsia since its inhibition using low dose aspirin has been shown to modify the disease in high risk pregnancies. PMID- 8369256 TI - The use of gemeprost pessaries to arrest postpartum haemorrhage. PMID- 8369257 TI - Pregnancy and ACE inhibitors. PMID- 8369258 TI - Cervical cancer: the diagnostic value of rectosonography for the judgement of parametrial invasion in regard of inflammatory stromal reaction. PMID- 8369259 TI - Sex hormone binding globulin concentrations in premenstrual syndrome. PMID- 8369260 TI - Epidemic of conjoined twins in Cardiff. PMID- 8369261 TI - Computerised and visual assessment of the cardiotocograph. PMID- 8369262 TI - Prevalence of hepatitis B and C viruses and human immunodeficiency virus infections in women of reproductive age. PMID- 8369263 TI - Long term follow up of women after hysterectomy with a history of pre-invasive cancer of the cervix. PMID- 8369264 TI - Long term follow up of women after hysterectomy with a history of pre-invasive cancer of the cervix. PMID- 8369265 TI - Antibiotic prophylaxis and caesarean section. PMID- 8369266 TI - Endometrial changes and lesions in postmenopausal women treated with tamoxifen. PMID- 8369267 TI - Neuroendocrine neoplasms of the lung. A 10 year perspective of their classification. AB - Based on clinical and pathologic data, neuroendocrine neoplasms of the bronchopulmonary tract may be classified into 3 groups: bronchial carcinoid; well differentiated neuroendocrine carcinoma (WDNC); poorly differentiated neuroendocrine carcinoma. The criteria of classification and the problems of multidirectional differentiation are discussed in detail. PMID- 8369268 TI - [Medullary thyroid carcinoma. Immunohistochemical markers in histopathology and research]. AB - Medullary thyroid carcinoma, a tumour derived from the calcitonin-producing C cells, is a rare tumour. Nevertheless it has evoked considerable interest in the past two decades amongst pathologists, clinicians, and human geneticists. Medullary thyroid carcinoma occurs either sporadically or as part of the inherited MEN II syndromes. The introduction of sensitive biochemical screening tests for the detection of early, clinically occult disease, and the advent of specific immunohistochemical staining methods have proved ideally for the study of this tumour. Immunohistochemical confirmation of the diagnosis of medullary thyroid carcinoma and the demonstration or exclusion of concomitant C cell hyperplasia (which precedes medullary thyroid carcinoma) are regarded as mandatory. Immunohistochemical markers used in routine histopathology and/or research of medullary thyroid carcinoma are reviewed and briefly discussed in the present paper. PMID- 8369269 TI - Functional-morphological effect of the synthetic atrial natriuretic factor (ANF 101-126) on the zona glomerulosa cells of adrenal cortex. AB - The effects of atrial natriuretic factor (ANF) on the adrenal steroidogenesis were examined in the zona glomerulosa of rats in vivo. ANF administration provoked a significant decrease in the width of zona glomerulosa (P < 0.01) and a significant enlargement of nuclei of zona glomerulosa cells (P < 0.01). Ultrastructurally conspicuous change was observed in mitochondria of the cells of the zona glomerulosa treated with ANF, representing elongated mitochondria with "parallel arrays" of tubules with pipe-like structure. In vitro autoradiography 125I-labelled ANF binding displayed a significant decrease of a specific receptor site in the zona glomerulosa treated with ANF. A significant lowering in plasma levels of aldosterone was observed in ANF-treated rats. These findings could be interpreted as an inhibitory effect of ANF on adrenal steroidogenesis of the glomerular zone by action through a specific ANF-receptor. PMID- 8369270 TI - [Neuroendocrine system and neuroendocrine tumors]. PMID- 8369272 TI - Mutational replacements of the amino acid residues forming the hydrophobic S4 binding pocket of subtilisin 309 from Bacillus lentus. AB - The amino acid side chains of Ile107, Leu126, and Leu135 participate in the formation of the important hydrophobic S4 binding pocket of the subtilisin Savinase. Ile107 and Leu126, located on each side of the pocket, point toward each other, and Leu135 is situated at the bottom of the pocket. These amino acid residues have been substituted for other hydrophobic amino acid residues by site directed mutagenesis, and the resulting enzymes have been characterized with respect to their P4 substrate preferences. The Leu126-->Ala or Phe substitutions reduce kcat/KM for the hydrolysis of all substrates to around 5% without altering the substrate preference. It is concluded that Leu126 is an essential structural part of the pocket which cannot be replaced without seriously affecting catalysis, consistent with the fact that Leu126 is conserved among all subtilisins. In contrast, the Ile107-->Gly, Ala, Val, Leu, or Phe and Leu135- >Ala, Val, or Phe substitutions strongly influence the P4 substrate preference, and some of the mutants exhibit large specificity changes for particular substrates when compared to wild-type Savinase. The results can be rationalized on the basis of Ile107 and Leu135 being responsible for steric repulsion of branched aliphatic and aromatic P4 side chains, respectively. Leu135 exclusively interacts with aromatic P4 side chains, and its replacement with less bulky amino acid residues alleviates steric repulsion such that the activity toward this type of substrates is enhanced. Conversely, the introduction of a more bulky amino acid residue at position 135 produces more steric repulsion and reduces the activity toward substrates with aromatic P4 side chains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369271 TI - 2'-Hydroxyl groups important for exon polymerization and reverse exon ligation reactions catalyzed by a group I ribozyme. AB - The functional importance of ribose moieties in both exons and in intron sequences proximal to the 3' splice site of a group I intron has been analyzed using a novel exon polymerization reaction. The ribozyme is a modified version of a self-splicing bacterial tRNA intron (I) that attacks a 20-nucleotide synthetic ligated exon substrate (E1.E2), yielding E1 and I.E2 by reverse exon ligation. A series of repetitive reactions then polymerize E2 on the 3' end of the intron; attack by E1 subsequently generates E1.(E2)n. Systematic deoxyribonucleotide substitution within E1.E2 was used to probe the function of 2'-hydroxyl groups in each exon and the 3'-terminal nucleotides of the intron. We find that ribose at the splice junction (U-1) and at the two adjacent positions with E1 (A-2, C-3) is important for reverse exon ligation. Within E2, deletion of 2'-hydroxyl groups of the nucleotides that form P10 does not affect reactivity. In contrast, ribose at the 3' end of the intron is essential for reverse exon ligation, and the presence of a 2'-OH group in each of the nucleotides comprising P9.0[3'] contributes to reaction efficiency. These results support a model in which specific 2'-hydroxyl groups at and adjacent to the reaction sites form tertiary contacts that serve to stabilize interactions with the catalytic core of the ribozyme. Furthermore, they suggest that the mechanism by which guanosine at the 3' end of the intron is activated for reverse exon ligation is the same as that by which guanosine mononucleotide is activated in the first step of splicing. PMID- 8369273 TI - Elucidation of anti-ssDNA autoantibody BV 04-01 binding interactions with homooligonucleotides. AB - Binding interactions of various synthetic oligohomonucleotides with anti-ssDNA autoantibody BV 04-01 (IgG2b, kappa) and the corresponding single-chain antibody (SCA) 04-01/212 were studied. Oligonucleotide binding to IgG or SCA resulted in quenching of the protein's tryptophan fluorescence permitting direct assessment of ligand binding under equilibrium conditions. The effect of oligothymidylate length, (dT)n, on tryptophan quenching was evaluated. The equilibrium dissociation constants (Kd) for the binding of (dT)6 and (dT)8 were the same [(1.3 +/- 0.02) x 10(-7) M], while decreasing the length of the oligothymidylate to (dT)3 increased the Kd an order of magnitude. To assess base specificity, the comparative binding of other hexahomonucleotides was examined. Neither (dA)6 nor (dC)6 showed measurable binding, while the dissociation constant for (dG)6 was (7.1 +/- 0.3) x 10(-7) M. Fluorescence lifetime quenching data correlated with the steady-state binding results and indicated that the quenching process contains both dynamic and static components. The ability of BV 04-01 to bind (dT)6 and (dG)6 nucleotides was further supported by fluorescence anisotrophy studies with fluorescein-labeled hexadeoxynucleotides. Various levels of tryptophan fluorescence quenching upon titration with oligothymidylates of different length, as well as the similar affinities for (dT)6 and (dG)6, supported the concept that the groove-type binding pocket in BV 04-01 consists of binding subsites that cooperatively adapt for efficient binding of oligonucleotides. PMID- 8369274 TI - A role for the epsilon-amino group of lysine-334 of ribulose-1,5-bisphosphate carboxylase in the addition of carbon dioxide to the 2,3-enediol(ate) of ribulose 1,5-bisphosphate. AB - Earlier structural and functional studies of ribulose-1,5-bisphosphate carboxylase/oxygenase imply that K334 facilitates the addition of gaseous substrate to the 2,3-enediol(ate) derived from ribulose 1,5-bisphosphate. Crystallographic analysis of the activated spinach enzyme [Knight et al. (1990) J. Mol. Biol. 215, 113-160] shows that the lysyl side chain is appropriately positioned to stabilize the transition state for the addition of CO2 to the enediol(ate). Furthermore, despite total impairment of carboxylase and oxygenase activities, site-directed mutants of the Rhodospirillum rubrum enzyme with replacements for lysine K334 (formerly designated K329) retain the capacity to enolize ribulose bisphosphate, demonstrating that the primary catalytic lesion lies beyond this initial step [Soper et al. (1988) Protein Eng. 2, 39-44; Hartman & Lee (1989) J. Biol. Chem. 264, 11784-11789]. We now show that the K334C mutant is also competent in the latter stages of catalysis, whereby 2'-carboxy-3-keto-D arabinitol 1,5-bisphosphate, the six-carbon intermediate of the carboxylation pathway, is correctly processed to 3-phosphoglycerate. Thus, the impairment of the mutant in overall catalysis can be attributed to preferential disruption of the reaction of CO2 or O2 with the enzyme-bound enediol(ate). Chemical rescue of the K334C mutant by aminoethylation and aminopropylation shows that this disruption reflects, at least in part, a failure to adequately stabilize the relevant transition state. With several simplifying assumptions, the CO2/O2 specificity factor tau can be reduced to the ratio of the fundamental second order rate constants for the interaction of the gaseous substrates with the enzyme-bound 2,3-enediol(ate) of ribulose bisphosphate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369275 TI - Oxidation of tetrahydrostilbazole by monoamine oxidase A demonstrates the effect of alternate pathways in the kinetic mechanism. AB - The steady-state kinetics for the oxidation of 1-methyl-1,2,3,6 tetrahydrostilbazole (MTHS) by purified human liver monoamine oxidase A yielded biphasic double-reciprocal plots. Rate constants from stopped-flow studies were determined to show that the apparent stimulation at high substrate concentrations can be explained in terms of the alternate oxidative pathways available to monoamine oxidase A [Ramsay, R. R. (1991) Biochemistry 30, 4624-4629]. At low substrate concentrations, the slower reoxidation of the free enzyme (second-order rate constant was 4000 M-1 s-1) predominates, but at higher concentrations the faster reoxidation of the reduced enzyme-substrate complex (38,300 M-1 s-1) becomes significant. Computer simulation using this model predicts that similar biphasic curves could be obtained for the oxidation of the neurotoxin, 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine, but that nonlinearity would be obvious only at concentrations above 200 Km. PMID- 8369276 TI - Crystallographic and fluorescence studies of the interaction of haloalkane dehalogenase with halide ions. Studies with halide compounds reveal a halide binding site in the active site. AB - Haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 catalyzes the conversion of 1,2-dichloroethane to 2-chloroethanol and chloride without use of oxygen or cofactors. The active site is situated in an internal cavity, which is accessible from the solvent, even in the crystal. Crystal structures of the dehalogenase enzyme complexed with iodoacetamide, chloroacetamide, iodide, and chloride at pH 6.2 and 8.2 revealed a halide binding site between the ring NH's of two tryptophan residues, Trp-125 and Trp-175, located in the active site. The halide ion lies on the intersection of the planes of the rings of the tryptophans. The binding of iodide and chloride to haloalkane dehalogenase caused a strong decrease in protein fluorescence. The decrease could be fitted to a modified form of the Stern-Volmer equation, indicating the presence of fluorophors of different accessibilities. Halide binding was much stronger at pH 6.0 than at pH 8.2. Assuming ligand binding to Trp-125 and Trp-175 as the sole cause of fluorescence quenching, dissociation constants at pH 6.0 with chloride and iodide were calculated to be 0.49 +/- 0.04 and 0.074 +/- 0.007 mM, respectively. Detailed structural investigation showed that the halide binding site probably stabilizes the halide product as well as the negatively charged transition state occurring during the formation of the covalent intermediate. PMID- 8369277 TI - Molecular organization and motions of cholesteryl esters in crystalline and liquid crystalline phases: a 13C and 1H magic angle spinning NMR study. AB - Cholesteryl esters are a major lipid constituent of plasma lipoproteins and atherosclerotic lesions. Crystalline and liquid crystalline phases of several cholesteryl esters [oleate (C18:1, omega-9), erucate (C22:1, omega-9), hexanoate (C6:0), decanoate (C10:0), undecanoate (C11:0), myristate (C14:0), palmitate (C16:0), and stearate (C18:0)] have been studied by natural abundance 13C NMR with magic angle spinning (MASNMR) at 75 MHz (7.05 T). Spectra obtained with magic angle spinning, high-power proton decoupling, and cross-polarization transfer were highly resolved for crystalline cholesteryl esters. Acyl chain carbons had narrower lines than protonated steroid ring carbons, reflecting differential motions in the crystal (specifically, more rapid motions in the acyl chain than in the steroid ring). Esters which crystallize into the monolayer type II structure, in which all molecules are equivalent, gave rise to a single resonance for each carbon; esters of the monolayer type I and bilayer structures, in which there are two types of nonequivalent molecules in the unit cell, had two resonances (equal intensity and line width) for several carbons, such as the carbonyl and the steroid ring C5 and C6. Spectra for liquid crystalline phases did not show inequivalence of signals for the same carbon and were not enhanced by cross-polarization transfer. These changes are a result of increased molecular motions in the liquid crystals, which average the nonequivalent environments and reduce the dipolar interactions. Cholesteric and smectic liquid crystalline phases were distinguished by the broader C = O, C5, and C6 signals for the cholesteric compared with the smectic phase. In the smectic phase, chemical shifts of corresponding carbons of all cholesteryl esters are similar and are close to those for crystalline esters with a monolayer II structure, which suggests that the smectic phase has structural features resembling the monolayer II crystal structure. 13C MASNMR is thus a powerful approach for examining structure and motions of crystalline and liquid-crystalline cholesteryl esters. 1H MASNMR spectra did not give as detailed information on the molecular level but were unique for each phase and provided a simple and quick method for distinguishing the solid, smectic, cholesteric, and isotropic phases. PMID- 8369278 TI - Solution structure of GCCAAT recognition motif by 2D NMR, spectral simulation, molecular modeling, and distance geometry calculations. AB - Solution conformation of a self-complementary 14-mer DNA duplex (d GGATTGGCCAATCC) containing the GCCAAT recognition motif of several transcription factors has been investigated by NMR spectroscopy. Complete resonance assignment of all the protons (except H5',H5'' protons) has been obtained following standard procedures based on two-dimensional NMR techniques. Three-bond coupling constants have been determined by spectral simulation procedures. New strategies have been described and employed for quantifying NOE intensities from the structural point of view. Approximate ranges of gamma torsion angles have been obtained from a selective NOESY experiment, by estimating the J(4'-5'), J(4'-5''), or their sum in the H1'-H4' cross peaks of the spectrum. Likewise, ranges of epsilon torsion angles have been obtained by monitoring the H3' multiplicities in the H8/H6-H3' cross peaks in selective NOESY spectra. With the help of such a total of 73 coupling constraints, 79 NOE intensity constraints, and 108 H-bond constraints, model building has been carried out to obtain a structure which satisfies the constraints. Starting from such a structure, an expanded distance constraint set has been created which has been used for the distance geometry calculations using the program TANDY. In the best structure thus derived, interesting irregularities similar to a BI-BII transition have been observed in the center. The molecule exhibits a bend. The overall base stacking is different from that in either B- or A-DNA models. The base pairs are tilted with respect to the local helix axes. The observed structural features are likely to have important implications for the recognition mechanism of the GCCAAT motif. PMID- 8369279 TI - Isolation of lambda repressor mutants with defects in cooperative operator binding. AB - A hybrid operator-promoter region was designed to aid in a screen for cooperativity mutants of the lambda repressor. In this system, lambda repressor mutants with defects in pairwise cooperative binding are unable to act as efficient transcriptional repressors. Four single amino acid substitutions in the C-terminal domain of the repressor were isolated. Studies of the DNA binding properties of the purified mutant proteins show that a repressor bearing the Gly147-->Asp mutation binds with normal affinity to single operator sites but is defective in pairwise cooperative site binding. Quantitative footprinting studies show that the free energy of interaction between repressor dimers bound at operator sites OR1 and OR2 is reduced from -2.4 kcal/mol for the wild-type repressor to 0 kcal/mol for the GD147 mutant. PMID- 8369280 TI - Factors participating in the liver-specific expression of the human apolipoprotein A-II gene and their significance for transcription. AB - We have shown previously that the hepatic and intestinal transcription of the human apolipoprotein A-II (apoA-II) gene in cell cultures is controlled by a complex set of regulatory elements A-N [Chambaz, et al. (1991) J. Biol. Chem. 266, 11676-11685; Cardot, et al. (1991) J. Biol. Chem. 266, 24460-24470]. In the present communication, we have assessed the functional importance of each of the regulatory elements. In addition, we have used DNA binding and competition assays and protein fractionation to identify the hepatic nuclear activities which are involved in the regulation of the human apoA-II gene. Such activities may be of general importance for the regulation of liver-specific genes. The DNA binding and competition analysis showed that the regulatory elements M, D, and F bind new activities which have not been identified in apolipoprotein or other liver specific promoters. These activities have been designated AIIM1 and AIIM2 for element M, AIID1 and AIID2 for element D, and AIIF2 for element F. The activity AIIM2 is present in liver, but absent in CaCo-2 cells. A set of regulatory elements binds activities which resemble liver-enriched or ubiquitous factors previously shown to play important roles in the regulation of their target genes. Thus, element I binds to activities related to NF1, and elements L, C, D, G, AB, and F bind to C/EBP alpha as well as other heat-stable activities. The affinity of the bacterially expressed C/EBP alpha for the various apoA-II regulatory regions follows the order: AIIL approximately AIIC > AIID > AIIF > AIIG > AIIAB. Protein fractionation showed that element J binds at least three hepatic nuclear activities and is also recognized by members of the nuclear receptor family, HNF4, EAR2, EAR3, and ARP1. Another liver-enriched factor, HNF1, was shown previously to bind to element H. Despite the importance of HNF1, HNF4, NF1, and C/EBP alpha in the regulation of numerous other target genes, deletion of the HNF1, NF1, and HNF4 and several C/EBP binding sites did not drastically affect the hepatic transcription of the apoA-II gene. Rather, the hepatic and intestinal transcription is affected severely by deletion of elements A, B, K, L, and N. In addition, the intestinal transcription is affected by deletion of elements C, J, and M. The in vivo physiological importance of these elements will require analysis of their function in transgenic animals. This analysis establishes the organization of several nuclear activities on the human apoA-II promoter.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8369281 TI - Footprinting titration studies on the binding of echinomycin to DNA incapable of forming Hoogsteen base pairs. AB - In order to investigate the possible importance of Hoogsteen base pairing to the DNA-binding ability of echinomycin, quantitative DNase I footprinting has been performed. The substrate was the tyrT DNA restriction fragment, either "native" or substituted with one of the purine analogs 2'-deoxy-7-deazaadenosine and 2' deoxy-7-deazaguanosine in both strands. The modified DNA species were prepared by PCR and selectively labeled at the 5' terminus of one strand (usually the upper "Watson" strand) with [32P]ATP and polynucleotide kinase. Proper incorporation of the analog nucleotides was verified by Maxam-Gilbert G- and C-sequencing reactions as well as exposure to osmium tetroxide and diethyl pyrocarbonate. OsO4 was found to react strongly with the 7-deaza nucleotides, providing a good check of faithful incorporation. The previously observed echinomycin-induced hyperreactivity of purines toward diethyl pyrocarbonate was eliminated by incorporating the appropriate 7-deazapurine. The DNase I footprinting titration studies greatly refined the existing knowledge of the DNA-binding characteristics of echinomycin, as they revealed five general types of concentration-dependent behavior at single-bond resolution. Estimates of microscopic binding constants at individual DNA binding sites were obtained by measuring the antibiotic concentration which produced a half-maximal effect on the concentration of a given DNase I cleavage product. All binding sites contained one or more CpG steps, and all CpG steps analyzed formed part of a binding site for echinomycin. No consistent differences in the estimated binding constants for these sites were observed by comparing normal and modified DNAs, indicating that the abolition of formal Hoogsteen pairs did not significantly alter the thermodynamics of echinomycin-DNA interaction. The lack of any detectable decrease in binding constants for critical sites in the 7-deazapurine-substituted DNAs argues against any anti-syn conformational transition of purine nucleosides occurring in association with the bis-intercalative complex formation. PMID- 8369282 TI - DNA interstrand cross-links induced by the cyclopropylpyrroloindole antitumor agent bizelesin are reversible upon exposure to alkali. AB - Bizelesin, a cyclopropylpyrroloindole (CPI) antitumor agent, has been shown to alkylate and cross-link DNA within A/T-rich tracts. Previous studies have shown that covalent reaction of the CPI adozelesin with DNA was reversible [Warpehoski, M. A., Harper, D. E., Mitchell, M. A., & Monroe, T. J. (1992) Biochemistry 31, 2502-2508]. That is, the monofunctional adduct could be lost from DNA, thus restoring the fidelity of DNA. In this study, we demonstrate that covalent DNA adducts induced by bizelesin at the adenine N3 position undergo two subsequent competing reactions: one which causes DNA strand cleavage, via depurination, and one which proceeds through loss of the DNA adduct (adduct reversal with restoration of DNA integrity). Our results were obtained by studying the chemical stability of synthetic DNA oligonucleotides which contained either a distinct DNA monofunctional adduct or DNA interstrand cross-links. Quantification of adduct reversal was performed on the basis that drug-modified DNA, upon exposure to heat followed by hot piperidine treatment, was resistant to strand cleavage at the site of alkylation. The rate of adduct reversal was found to increase with increasing temperature and was found to be maximum at 70-80 degrees C. The rate of adduct reversal was also found to increase with increasing pH and ionic strength. In contrast, the rate of depurination and subsequent DNA strand cleavage decreased as pH and ionic strength were increased. Adduct reversal was favored in DNA containing interstrand cross-links, whereas rapid depurination occurred preferentially within monofunctionally alkylated DNA. PMID- 8369284 TI - Hypersensitivity of an enzyme reaction to solvent water. AB - The hydrolytic activity of calf intestinal adenosine deaminase is reduced sharply, but reversibly, in the presence of added methanol, ethanol, acetonitrile, or dioxane. This decrease in kcat/Km appears to be related to diminished water content in the presence of each of these cosolvents. No agreement between cosolvents is observed if enzyme activity is plotted as a function of viscosity or dielectric constant; nor do these cosolvents act as conventional reversible inhibitors. The Km value of adenosine and the Ki values of a substrate analogue (6-dimethylaminopurine ribonucleoside) and a powerful competitive inhibitor (6-hydroxy-1,6-dihydropurine ribonucleoside) increase with decreasing solvent water content, but kcat is unaffected. Values of 1/Km and 1/Ki increase with roughly the 9th power of the concentration of water and show no sign of approaching a maximum value as the concentration of water approaches 55 M. These results are consistent with an equilibrium between an abundant, inactive, relatively dehydrated form of the enzyme and a rare, relatively hydrated form of the enzyme. Only the hydrated form of the enzyme, containing at least nine more water molecules than the dehydrated form, appears to be capable of binding substrates or competitive inhibitors. Possible physiological consequences of this behavior, in a tissue in which water is transported in large quantities, are considered. PMID- 8369283 TI - Selection and characterization of a mutant T7 RNA polymerase that recognizes an expanded range of T7 promoter-like sequences. AB - The compatible plasmids pKGP1-1 and pCM-X# will confer chloramphenicol resistance to Escherichia coli harboring the two plasmids if the T7 RNA polymerase produced from pKGP1-1 can recognize the T7 promoter carried on pCM-X# and transcribe the CAT gene that is cloned behind the promoter [Ikeda et al. (1992) Biochemistry 31, 9073-9080]. When E. coli harbor pKGP1-1 and a pCM-X# plasmid that carries a point mutation in the T7 promoter that destroys promoter activity (an inactive pCM-X#), the T7 RNA polymerase will not utilize the T7 promoter point mutant, will not produce CAT, and will not induce chloramphenicol resistance. The selection of mutants of T7 RNA polymerase that exhibit altered promoter recognition was pursued by randomly mutagenizing pKGP1-1 with aqueous hydroxylamine, cotransforming E. coli with the mutagenized pKGP1-1 and a mixture of seven different inactive pCM-X# plasmids, and isolating and characterizing the RNA polymerase that was present in those colonies that exhibited chloramphenicol resistance. It was established that E. coli harboring the mutant plasmid pKGP HA1mut4 and an inactive pCM-X# are chloramphenicol-resistant and that the mutation responsible for the expression of CAT from the inactive pCM-X# plasmid is a G to A transition at nucleotide 664 of T7 gene 1 that converts glutamic acid (222) to lysine. Apparently this mutation expands the range of T7 promoter sequences that can be utilized by the enzyme. The mutant T7 RNA polymerase, GP1(Lys222), utilizes all seven inactive T7 promoter point mutants more efficiently than wild-type T7 RNA polymerase both in vivo and in vitro. Furthermore, the correlation of in vivo and in vitro promoter utilization suggests that the restoration of chloramphenicol resistance in the cotransformed E. coli results from the ability of GP1(Lys222) to initiate transcription from T7 promoter point mutants that are normally inactive. PMID- 8369285 TI - Simple centrifugation method for efficient pelleting of both small and large unilamellar vesicles that allows convenient measurement of protein binding. AB - Separation of unilamellar model membrane vesicles from external solution is often an important step in quantitation of vesicle bound or entrapped materials. An efficient method that allows pelleting of both small and large model membrane vesicles by centrifugation is described in this report. In this method streptavidin is added to vesicles containing a trace amount of biotinylated lipid. The resulting aggregation allows pelleting of the vesicles using an ordinary high-speed centrifuge. Control experiments show that the addition of streptavidin does not induce substantial vesicle fusion or leakage of substances trapped in the internal aqueous compartment of the vesicles. The method can accommodate different phospholipid compositions and lipid concentrations. Experiments with proteins that switch between hydrophilic and hydrophobic states show that the method can readily be used to monitor protein binding to vesicles. PMID- 8369286 TI - Luminescence studies with trp repressor and its single-tryptophan mutants. AB - Time-resolved and steady-state fluorescence, low-temperature phosphorescence, and optically detected magnetic resonance (ODMR) measurements have been made to resolve the luminescence contributions of the two intrinsic tryptophan residues in the subunits of trp aporepressor from Escherichia coli. Assignments of spectral information have been confirmed by use of the single-tryptophan mutants W19F and W99F. Solute fluorescence quenching studies show that both Trp19 and Trp99 are exposed to acrylamide and iodide, with Trp99 being the more exposed. Time-resolved and steady-state fluorescence measurements show Trp19 to have a bluer emission, a longer mean fluorescence decay time, a higher quantum yield, and essentially no independent rotational motion with respect to the protein. Trp99 is found to have a redder emission, a shorter mean fluorescence decay time, a lower quantum yield, and a significant degree of rotational freedom. Phosphorescence studies show a clear resolution of 0-0 vibronic transitions for each type of residue, with maxima at 407 and 415 nm that are assigned to Trp19 and Trp99, respectively. ODMR measurements show the zero-field splitting parameters to be quite characteristically different for each tryptophan residue. The existence of resonance energy transfer from Trp19 to Trp99, in the wild-type protein, is indicated by three types of data: comparison of the long-lived decay time (attributed to Trp19) in the absence (W99F) and presence (wild type) of the acceptor Trp99, comparison of the fluorescence quantum yield of the wild-type and mutant proteins, and deviations from the expected phosphorescence intensities for Trp19 and Trp99 in the absence of energy transfer. PMID- 8369287 TI - Cytochrome P450 hydroxylation of hydrocarbons: variation in the rate of oxygen rebound using cyclopropyl radical clocks including two new ultrafast probes. AB - The oxidation of eight methyl-substituted and three alkyl-substituted cyclopropanes by rat liver microsomal cytochrome P450 and pure reconstituted rabbit P450 2B4 was studied. Alkane hydroxylation catalyzed by P450 is generally believed to proceed by hydrogen abstraction followed by reaction of the carbon centered radical with an iron-bound hydroxyl radical, a process called oxygen rebound. Hydrogen abstraction from methylcyclopropanes generates cyclopropylcarbinyl radicals whose solution rate constants for ring opening are known [Bowry, V.W., et al. (1991) J. Am. Chem. Soc. 113, 5687-5698]. Rearranged products were only observed with the five substrates which, upon hydrogen abstraction, would generate a cyclopropylcarbinyl radical that undergoes ring opening with a rate constant > or = 2.0 x 10(9) s-1 in solution. Values of the rate constants for oxygen rebound (kOH) were calculated by determining the ratio of unrearranged products (cyclopropylmethanols) to rearranged products (alkenols). For each substrate this ratio was generally about the same for the oxidations catalyzed by microsomal P450 and by P450 2B4. It is concluded that all of the substrates are oxidized via an intermediate cyclopropylcarbinyl radical. Two ultrafast probes, trans-1-methyl-2-phenylcyclopropane and 1,1-diphenyl-2 methylcyclopropane, gave alcohol product ratios which yielded unreasonably high values for kOH, viz., ca. 1.5 x 10(12) and ca. 7 x 10(12) s-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369288 TI - Acrylodan can label amino as well as sulfhydryl groups: results with low-density lipoprotein, lipoprotein[a], and lipid-free proteins. AB - Human plasma lipoprotein[a] and autologous low-density lipoprotein were reacted with the fluorescent probe 6-acryloyl-2-(dimethylamino)naphthalene (acrylodan) previously reported to be specific for sulfhydryl groups. Reaction kinetics were biphasic in both cases. The reaction of bovine serum albumin with acrylodan was also biphasic. Monophasic kinetics were observed when protein free sulfhydryl groups were blocked by carboxamidomethylation prior to acrylodan reaction. A significant increase in total fluorescence was observed in the reaction of acrylodan with proteins containing no free sulfhydryl groups and with polylysine. The rates of these reactions were highly sensitive to pH. Fluorescence changes due to dissolution of probe into hydrophobic protein or lipid domains were minimal as was reaction of probe with phospholipid head groups. When isolated from acrylodan-labeled Lp[a], apo[a], which contains no free sulfhydryl groups, contained covalently bound acrylodan. These results suggest that acrylodan can modify the lysine residues of lipid-free proteins and may modify not only the free sulfhydryl groups of low-density lipoprotein and lipoprotein[a] but also reactive amino groups. We conclude that under these conditions, the use of this probe to quantify free sulfhydryl groups in these lipoproteins is infeasible. PMID- 8369289 TI - Structure of novel gangliosides, deaminated neuraminic acid (KDN)-containing glycosphingolipids, isolated from rainbow trout ovarian fluid. AB - Two acidic glycosphingolipids were isolated and purified from rainbow trout ovarian fluid. They were designated as ovarian fluid gangliosides ofg-2a and ofg 2b. Both of these glycolipids were found to contain glucose, galactose, and N acetylgalactosamine in a molar ratio of 1:2:1, but they differ by the presence of 2 mol of deaminated neuraminic acid (KDN; 2-keto-3-deoxy-D-glycero-D-galacto nononic acid) in ofg-2a and 1 mol each of KDN and 9-O-acetyl-KDN in ofg-2b. On the basis of composition analysis, methylation analysis, mild acid hydrolysis, fast atom bombardment mass spectrometry (FABMS), 400-MHz 1H nuclear magnetic resonance spectroscopy, and immunochemical analysis using a monoclonal antibody (mAb.kdn3G), the complete structures of these gangliosides were determined to be KDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2a [(KDN)GD1a] and 9-O-AcKDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2b [(KDN)GD1a(OAc+)]. The ceramide moieties (Cer) in both ofg-2a [(KDN)GD1a] and ofg 2b [(KDN)GD1a(OAc+)] were found by combining of the results from fatty acid analysis and FABMS measurements to be made up of 4-sphingenine and mainly a C24:1 fatty acyl chain (nervonate). The structures of ofg-2a and ofg-2b are novel, and they represent the second example of naturally occurring KDN-gangliosides. Mild acid hydrolysis of both ofg-2a and ofg-2b resulted in formation of (KDN)GM1a. PMID- 8369290 TI - Demonstration of a two-step reaction mechanism for the inhibition of heparin bound neutrophil elastase by alpha 1-proteinase inhibitor. AB - Heparin decreases the rate of inhibition of neutrophil elastase by alpha 1 proteinase inhibitor as a result of its strong binding to the enzyme. Here, we used the slow-binding kinetic approach to decide whether the enzyme-inhibitor interaction proceeds via a two-step mechanism and to identify the step that is affected by heparin. The inhibition kinetics was assessed under pseudo-first order conditions using conventional or stopped-flow spectrophotometry. In the absence of heparin, the pseudo-first-order rate constant of inhibition increased linearly with the inhibitor concentration indicating that within the experimental concentration range (< or = 6 microM) the enzyme-inhibitor association conforms either to a simple bimolecular reaction (E+I kass-->EI with kass = 10(7) M-1 s-1) or to a two-step reaction (E+I Ki*<==>EI* k2-->EI with Ki* > 0.4 microM and k2 > 4 s-1). In the presence of heparin, the rate constant of inhibition varied hyperbolically with the inhibitor concentration, indicating that the inhibition is a two-step process with Ki* = 80 nM and K2 = 0.15 s-1. Thus, heparin has two opposite effects on the elastase + alpha 1-proteinase inhibitor interaction: it favors the association by decreasing Ki* but impairs it by decreasing k2. This rationalizes the previously demonstrated rate-depressing effect of the sulfated polymer. Heparin does not significantly alter the stability of the irreversible elastase-alpha 1-proteinase inhibitor complex. PMID- 8369291 TI - Identification of a second rat pancreatitis-associated protein. Messenger RNA cloning, gene structure, and expression during acute pancreatitis. AB - The pancreatitis-associated protein (PAP) is a lectin-related secretory protein present in small amounts in the rat pancreas and overexpressed during the acute phase of pancreatitis. On the other hand, PAP is constitutively expressed in the intestinal tract but not in other tissues. We cloned from a pancreatic cDNA library two overlapping cDNAs encoding a protein structurally related to PAP. This second PAP, which was called PAP II, was the same size as the original PAP (PAP I) and showed 74.3% amino acid homology. Studies on gene expression demonstrated that PAP II mRNA concentration increased within 6 h following induction of pancreatitis, reached maximal levels (> 200 times control values) at 24-48 h, and decreased thereafter, similar to PAP I. However, PAP II mRNA could not be detected in the intestinal tract or in other tissues. We also isolated a PAP II genomic DNA fragment which was characterized over 2.7 kb of gene sequence and 1.9 kb of 5' flanking sequence. The 5' end of the coding sequence was determined by primer extension of the PAP II mRNA. The PAP II coding sequence spanned six exons separated by five introns. Several potential regulatory elements were identified in the promoter region, including two glucocorticoid response elements and one IL-6-response element. Antibodies raised to a synthetic peptide of PAP II detected a single band in Western blot analysis of the pancreatic secretory proteins from rats with pancreatitis, with a M(r) compatible with the theoretical M(r) of PAP II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369292 TI - Tissue- and development-specific expression in transgenic mice of a type I procollagen (COL1A1) minigene construct with 2.3 kb of the promoter region and 2 kb of the 3'-flanking region. Specificity is independent of the putative regulatory sequences in the first intron. AB - Previous reports have provided inconsistent data as to the cis-regulatory elements that are essential for correct expression of the gene for the pro alpha 1 (I) chain of type I procollagen (COL1A1) in the many tissues in which the protein is synthesized. Here, two internally deleted minigene versions of the human COL1A1 gene were used to prepare transgenic mice. The constructs made it possible to test regulatory sequences in the normal context of the gene. Also, in contrast to the reporter genes used in previous experiments, the constructs made it possible to assay quantitatively expression of the exogenous genes relative to expression of the endogenous COL1A1 gene, both as mRNA and as protein. The average level of expression of the minigenes varied among three transgenic lines, but the ratio of expression of the minigenes to expression of the endogenous gene was the same in all transgenic mice of a given line. Within the same line, the ratio of expression was essentially the same in nine or more tissues in which expression of the endogenous gene varied widely. Also, the ratio of expression within a given line was the same in 15-day-old embryos and in mice ranging in age from 4 days to 4 months. In addition, the ratio remained constant during repair of a surgical wound. The results demonstrated, therefore, that the minigene constructs with about 2.3 kb of the promoter region and about 2 kb of the 3' flanking region contained all of the sequences necessary for correct expression of the genes in a tissue-specific and development-specific manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369293 TI - Purification and characterization of Bacillus subtilis CheY. AB - Amino acid sequence comparison suggests that numerous proteins are common to the signal transduction pathways controlling chemotaxis in Bacillus subtilis and Escherichia coli. However, previous work has indicated several differences between the two systems. We have undertaken a comparative study of the roles of the CheY protein in chemotaxis by B. subtilis and E. coli. Although CheY from the two species share only 36% amino acid sequence identity, purified B. subtilis CheY was phosphorylated in vitro by E. coli CheA, and dephosphorylation of CheY-P was enhanced by E. coli CheZ. Alteration of the putative site of phosphorylation in B. subtilis CheY, Asp54, eliminated chemotaxis in vivo, further confirming that phosphorylation is important for B. subtilis chemotaxis. Loss of CheY function resulted in tumbling behavior in B. subtilis. Introduction of positively charged residues in place of Asp10 of B. subtilis CheY abolished function, whereas the corresponding changes in E. coli CheY apparently result in constitutive activation. The B. subtilis CheY Asp10 mutant proteins also failed to cause tumbling in E. coli, consistent with a different interaction between CheY and the flagellar switch in the two species. Finally, B. subtilis adapted more rapidly to positive stimuli than negative stimuli, whereas the opposite is true of E. coli. We conclude that B. subtilis regulates its response to positive chemotactic stimuli by enhancing phosphorylation of chemotaxis proteins, whereas E. coli reduces phosphorylation in the same circumstance. PMID- 8369294 TI - Exclusion of 2'-deoxycytidine 5'-monophosphate by asparagine 229 of thymidylate synthase. AB - In thymidylate synthase (TS, EC 2.1.1.45), the only side chain in direct hydrogen bonding with the pyrimidine ring of the substrate dUMP is asparagine 229 (N229). In binary and ternary complexes, the carboxamide moiety of the side chain of N229 forms a cyclic hydrogen bond network bridging N-3 and O-4 of the uracil heterocycle. Most of the N229 mutants of TS bind dUMP and catalyze dTMP formation as well as the wild-type enzyme; thus, N229 does not contribute to binding of dUMP. Wild-type TS binds dCMP weakly and does not accept dCMP as a substrate. Mutations at N229 of TS modify the interaction of TS with dCMP. TS N229D and TS N229E catalyze the methylation of dCMP [Liu, L., & Santi, D. V. (1992) Biochemistry 31, 5010-5014]. With the exception of the TS N229Q, most of the N229 mutants bind dCMP as well as or tighter than dUMP and bind dCMP 300-3000-fold tighter than wild-type TS. We conclude that TS discriminates binding of dUMP versus dCMP by a 3-4 kcal mol-1 difference in binding energy by exclusion of dCMP from the active site. We propose that this exclusion is a consequence of untoward interactions between dCMP and the side-chain carboxamide group of the Asn or Gln at position 229 of TS. We speculate that exclusion of cytosine versus uracil by Asn or Gln may account for specificity observed in other protein-pyrimidine interactions. PMID- 8369295 TI - A fluorescence spectroscopic study of substrate-induced conformational changes in glutaminyl-tRNA synthetase. AB - Glutaminyl-tRNA synthetase from Escherichia coli is a member of a subgroup of aminoacyl-tRNA synthetases that do not catalyze ATP-PPi exchange in the absence of the cognate tRNA. Such behavior suggests conformational changes upon substrate binding. Two different fluorescent probes, pyrenylmaleimide and acrylodan, were used to specifically label a nonessential sulfhydryl group of GlnRS. Conformational changes induced by substrates were studied using glutaminyl-tRNA synthetase labeled with these two environment-sensitive probes. ATP was shown to cause a significant conformational change that alters the mode of binding to tRNA(Gln) to GlnRS. The alteration of the salt sensitivity pattern of tRNA(Gln) binding to GlnRS by ATP supports this. Binding of tRNA(Gln) causes a conformational change that may be different in nature for the ATP/GlnRS complex and free GlnRS. Hydrodynamic parameters deduced from fluorescence polarization studies and the use of a noncovalent probe indicate that the ATP-induced conformational change may not be global in character. PMID- 8369297 TI - Assignment of enzymatic function to specific protein regions of cobalamin dependent methionine synthase from Escherichia coli. AB - Cobalamin-dependent methionine synthase catalyzes methyl group transfer from methyltetrahydrofolate to homocysteine to form tetrahydrofolate and methionine, and the cobalamin prosthetic group serves as an intermediate methyl carrier. Enzyme possessing cobalamin in the cobalt(II) oxidation state is inactive, and this form is activated by one-electron reduction coupled to methylation by S adenosylmethionine (AdoMet). The enzyme from Escherichia coli has been divided into separable fragments by limited proteolysis with trypsin, and the contribution of each of these fragments to substrate binding and catalysis has been evaluated. The 37.7-kDa carboxyl-terminal domain binds AdoMet, and this was demonstrated through covalent modification with radiolabeled AdoMet during ultraviolet irradiation. Following reductive activation with AdoMet, the enzyme was digested with trypsin and a 98.4-kDa amino-terminal fragment was isolated. It retained at least 70% of the activity of the intact enzyme and must therefore possess determinants sufficient for the binding of methyltetrahydrofolate and homocysteine, as well as residues required for catalysis. However, when the cobalamin was oxidized to the cob(II) alamin state, the 98.4-kDa fragment could not be reductively remethylated with AdoMet. A purified, 28-kDa domain within the 98.4-kDa fragment retained bound cobalamin and therefore must play a central role in catalysis, but the isolated 28-kDa domain retained no catalytic activity. Because AdoMet binds to a different domain of the protein than methyltetrahydrofolate and homocysteine, the enzyme probably uses conformational flexibility to allow the cobalamin access to the required methyl donor or acceptor at the appropriate time in catalysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369296 TI - Electrospray mass spectrometric analysis of the domains of a large enzyme: observation of the occupied cobalamin-binding domain and redefinition of the carboxyl terminus of methionine synthase. AB - Cobalamin-dependent methionine synthase from Escherichia coli catalyzes the methylation of homocysteine to form methionine, using methyltetrahydrofolate as the primary methyl donor. We have used electrospray mass spectrometry as a powerful tool for characterizing separable fragments obtained by proteolysis of this monomeric 136.1-kDa enzyme. A central 28.0-kDa domain, reported to bind the cobalamin, has been purified to homogeneity in 30% yield. We were able to detect the domain with bound cobalamin by electrospray mass spectrometry at neutral pH. Mass analysis of a 37.2-kDa carboxyl-terminal domain was grossly inconsistent with either of the two amino acid sequences from previously published DNA sequences. We then used electrospray mass spectrometry to analyze peptides generated by a lysyl endoproteolytic digest of a C-terminal fragment, and we have constructed a peptide map that accounts for > 95% of the peptide mass derived from this domain. The correct translational end of this protein (27 residues downstream from the previously predicted ultimate residue) has been established, and sequence conflicts within the two published DNA sequences have been resolved (GenBank Accession Number J04975). Resequencing the DNA near the carboxyl terminus ruled out a frameshifted reading of the DNA and suggested that a cytosine had twice been incorrectly inserted late in the reading frame. The strategies reported here for sequence confirmation, localization of coenzyme binding regions, and identification of chemically modified peptides within a large protein are potentially applicable to the characterization of many other proteins. PMID- 8369298 TI - Isolation of bovine kidney leucine aminopeptidase cDNA: comparison with the lens enzyme and tissue-specific expression of two mRNAs. AB - Aminopeptidases catalyze the hydrolysis of amino acid residues from the amino terminus of peptide substrates. Leucine aminopeptidase (LAP) from bovine lens is the best characterized aminopeptidase and the only LAP for which the amino acid sequence was determined by protein sequencing. Using this sequence information, we isolated a bovine kidney LAP cDNA and compared its deduced amino acid sequence to the published amino acid sequence for bovine lens LAP. Overall, the sequences are highly conserved. However, several differences are observed. The kidney LAP cDNA indicates a 26 amino acid extension at the amino terminus which is not found in the mature purified lens LAP. The cDNA also indicates an additional octapeptide in the C-terminal region which was not indicated in the published lens LAP amino acid sequence but which was required for best fit of crystallographic data regarding bovine lens LAP. Several other single amino acid changes were also noted. Levels of LAP transcripts were examined in bovine lens and kidney tissue as well as in cultured lens cells. Lens epithelial tissue showed only one LAP transcript (2.4 kb) whereas two transcripts (2.0 and 2.4 kb) were observed in cultured lens cells derived from epithelial tissue and in kidney tissue. Using Northern blot analysis, we correlated LAP mRNA levels with previously determined changes of LAP activity in aging lens tissue and in progressively passaged lens epithelial cells which were used to simulate aging in vitro. No differences were found in LAP mRNA levels in epithelial tissue from old and young lenses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369299 TI - Kinetic mechanism of Escherichia coli isocitrate dehydrogenase. AB - The kinetic mechanism of the NADP-dependent isocitrate dehydrogenase of Escherichia coli was investigated using initial steady-state kinetic analyses. Kinetic coefficients, obtained using natural and alternative substrates with the wild-type and two mutant enzymes (S113L and S113N), suggest that the forward reaction [the oxidative decarboxylation of (2R,3S)-isocitrate by NADP] of the wild-type enzyme is a steady-state random mechanism, with catalysis more rapid than product release. The mechanism of the wild-type enzyme becomes rapid equilibrium random when an alternative substrate [(2R)-malate or NAD] is used. The mutant enzymes always display rapid-equilibrium random kinetics, and for each enzyme the apparent dissociation constant of each substrate from the binary complex [Kia = E.A/(EA)] is similar to its apparent dissociation constant from the Michaelis complex [Ka = (EB).A/(EAB)], which suggests that the binding of one substrate is independent of the binding of the second. When the wild-type enzyme catalyzes the forward reaction, the apparent dissociation constant, KiIso, is equal to its equilibrium dissociation constant, KdIso, determined from equilibrium binding studies. However, the apparent dissociation constant of the cofactor, KiNADP, is far smaller than its equilibrium dissociation constant, KdNADP. This is consistent with the proposed mechanism, because simulations show that when catalysis is steady-state and product release is rate-limiting, KiNADP and KNADP will be far smaller than KdNADP, while KiIso and KIso remain similar to KdIso. Product inhibition studies support the steady-state random mechanism of the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369300 TI - Structure of isocitrate dehydrogenase with isocitrate, nicotinamide adenine dinucleotide phosphate, and calcium at 2.5-A resolution: a pseudo-Michaelis ternary complex. AB - The structure of isocitrate dehydrogenase (IDH) with a bound complex of isocitrate, NADP+, and Ca2+ was solved at 2.5-A resolution and compared by difference mapping against previously determined enzymatic complexes. Calcium replaces magnesium in the binding of metal-substrate chelate complex, resulting in a substantially reduced turnover rate. The structure shows the following: (i) A complete, structurally ordered ternary complex (enzyme, isocitrate, NADP+, and Ca2+) is observed in the active site, with the nicotinamide ring of NADP+ exhibiting a specific salt bridge with isocitrate. The binding of the cofactor nicotinamide ring is dependent on this interaction. (ii) Isocitrate is bound by the enzyme with the same interactions as those found for the magnesium/substrate binary complex, but the entire molecule is shifted in the active site by approximately 1 A in order to accommodate the larger metal species and to interact with the nicotinamide ring. The distances from isocitrate to the bound calcium are substantially longer than those previously found with magnesium. (iii) NADP in the Escherichia coli IDH has a novel binding site and conformation as compared to previously solved dehydrogenases. (iv) The orientation and interactions of the nicotinamide ring with the substrate are consistent with the stereospecificity of the enzyme-catalyzed reaction. PMID- 8369301 TI - Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate. AB - The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. The alpha ketoglutarate binds in the active site at the same position and orientation as isocitrate, with a difference between the two bound molecules of about 0.8 A. The Ca2+ metal is coordinated by alpha-ketoglutarate, three conserved aspartate residues, and a pair of water molecules. The largest motion in the active site relative to the isocitrate enzyme complex is observed for tyrosine 160, which originally forms a hydrogen bond to the labile carboxyl group of isocitrate and moves to form a new hydrogen bond to Asp 307 in the complex with alpha ketoglutarate. This triggers a number of significant movements among several short loops and adjoining secondary structural elements in the enzyme, most of which participate in dimer stabilization and formation of the active-site cleft. These rearrangements are similar to the ligand-binding-induced movements observed in globins and insulin and serve as a model for an enzymatic mechanism which involves local shifts of secondary structural elements during turnover, rather than large-scale domain closures or loop transitions induced by substrate binding such as those observed in hexokinase or triosephosphate isomerase. PMID- 8369302 TI - Kinetic analysis of NAD(+)-isocitrate dehydrogenase with altered isocitrate binding sites: contribution of IDH1 and IDH2 subunits to regulation and catalysis. AB - NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae is an allosterically regulated enzyme that exists as an octamer composed of two nonidentical subunits, designated IDH1 and IDH2. To determine the contribution of each subunit to regulation and catalysis, a conserved serine residue at the proposed active site of each subunit was mutated to alanine. This mutation in IDH1 resulted in a 6-fold decrease in Vmax and a decrease in cooperativity, but little change in S0.5 for isocitrate. The mutant IDH2, in contrast, exhibited a 60-fold decrease in maximal velocity and a 2-fold reduction in S0.5 for isocitrate, but the cooperativity was unaffected. Responses to the allosteric modifier AMP also differed for the two mutant enzymes. The IDH1 mutant enzyme was not activated by AMP, whereas the IDH2 mutant enzyme exhibited an increase in isocitrate affinity in the presence of AMP similar to that observed with the wild type enzyme. On the basis of these kinetic results, a model is presented which proposes that IDH1 functions as a regulatory subunit while IDH2 functions in catalysis. To determine if IDH1 or IDH2 alone is catalytically active, we also expressed the individual subunits in yeast strains in which the gene encoding the other subunit had been disrupted. Mitochondrial extracts from strains overexpressing solely IDH1 or IDH2 contained no detectable activity in the presence or absence of AMP. Gel filtration of these extracts showed that both IDH1 and IDH2 behaved as monomers, suggesting that the major subunit interactions within the octamer are between IDH1 and IDH2. PMID- 8369303 TI - Covalent bond changes as a driving force in enzyme catalysis. AB - A procedure is developed for assessing covalent and noncovalent aspects of the acylation of alpha-chymotrypsin (alpha-Ct) by the substrate trifluoroethyl furoate (S) to form furoyl-chymotrypsin (F-Ct) and trifluoroethanol (P1). The free energy change (-4.31 kcal/mol) for the acylation at pH 7, alpha-Ct+S <--> F Ct+P1, contains contributions from covalent bond changes as well as noncovalent changes. The noncovalent changes are considered to be manifested in the structures of alpha-Ct and F-Ct, and a noncovalent free energy difference between alpha-Ct and F-Ct has been evaluated from the difference in unfolding free energy changes for these proteins. The unfolding free energy changes demonstrate that F Ct is 1.6 kcal/mol less stable than alpha-Ct at pH7. Thus, despite an overall favorable free energy change for acyl-enzyme formation (-4.31 kcal/mol), covalent linkage of the furoyl moiety to the active site is thermodynamically destabilizing to the enzyme. The consequence of this unfavorable effect of the furoyl moiety on the noncovalent free energy is that "binding" of the covalently linked furoyl moiety cannot be the driving force for acylation. The source of free energy driving acylation is the covalent bond-breaking and bond-making involved in transesterification of the furoyl group to the enzyme. Since the (noncovalent) Michaelis complex between alpha-Ct and substrate is significantly more stable (thermodynamically) than F-Ct, a substantial amount of noncovalent free energy must be given up on forming F-Ct. The destabilization residing in F Ct is consistent with the possibility that energy transduction occurs when the Michaelis complex is converted to F-Ct and that destabilization is relieved on reaching the next activated complex. PMID- 8369304 TI - Active site labeling of the Yersinia protein tyrosine phosphatase: the determination of the pKa of the active site cysteine and the function of the conserved histidine 402. AB - In this report, we demonstrated that the Yersinia protein tyrosine phosphatase (PTPase) could be inactivated by the alkylating agent iodoacetate. The enzyme modification was selective, and the covalent attachment was stoichiometric. The residue that was labeled by iodoacetate was shown to be Cys403, which was the same catalytically essential residue identified by site-directed mutagenesis [Guan, K. L., & Dixon, J.E. (1990) Science 249, 553-556]. The rate of iodoacetate modification decreased as the ionic strength of the media increased. There was no significant D2O solvent isotope effect associated with the inactivation of the enzyme, suggesting that thiol anion of Cys403 reacted as a nucleophile. The Yersinia PTPase also displayed differential reactivity (940-fold) toward iodoacetate over iodoacetamide. This indicates that residues within the active site of the enzyme are positively charged. The pKa of the active site thiol group was determined to be 4.67. The low pKa value suggests that ionic interactions are important in stabilizing the thiolate anion. One candidate residue for this stabilization is the invariant histidine (His402) found in all PTPases. Substitutions of His402 with Asn or Ala altered the active site thiol pKa to 5.99 and 7.35, respectively. Interestingly, the active site thiol in the mutants also showed enhanced reactivity toward iodoacetate. The second-order rate constants for the inactivation of the wild-type enzyme, H402N, and H402A were 59.7, 3305, and 1763 M-1 min-1, respectively. PMID- 8369305 TI - Amino acid residues in Anabaena ferredoxin crucial to interaction with ferredoxin NADP+ reductase: site-directed mutagenesis and laser flash photolysis. AB - Ferredoxin (Fd) functions in photosynthesis to transfer electrons from photosystem I to ferredoxin-NADP+ reductase (FNR). We have made several site directed mutants of Anabaena 7120 Fd and have used laser flash photolysis to investigate the effects of these mutations on the kinetics of reduction of oxidized Fd by deazariboflavin semiquinone (dRfH.) and the reduction of oxidized Anabaena FNR by reduced Fd. None of the mutations influenced the second-order rate constant for dRfH. reduction by more than a factor of 2, suggesting that the ability of the [2Fe-2S] cluster to participate in electron transfer was not seriously affected. In contrast, a surface charge reversal mutation, E94K, resulted in a 20,000-fold decrease in the second-order rate constant for electron transfer from Fd to FNR, whereas a similar mutation at an adjacent site, E95K, produced little or no change in reaction rate constant compared to wild-type Fd. Such a dramatic difference between contiguous surface mutations suggests a very precise surface complementarity at the protein-protein interface. Mutations introduced at F65 (F65I and F65A) also decreased the rate constant for the Fd/FNR electron transfer reaction by more than 3 orders of magnitude. Spectroscopic and thermodynamic measurements with both the E94 and F65 mutants indicated that the kinetic differences cannot be ascribed to changes in gross conformation, redox potential, or FNR binding constant but rather reflect the protein-protein interactions that control electron transfer. Several mutations at other sites in the vicinity of E94 and F65 (R42, T48, D68, and D69) resulted in little or no perturbation of the Fd/FNR interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369306 TI - Reductive dehalogenation by cytochrome P450CAM: substrate binding and catalysis. AB - Biological reductive dehalogenation reactions are important in environmental detoxification of organohalides. Only scarce information is available on the enzymology underlying these reactions. Cytochrome P450CAM with a known X-ray structure and well-studied oxygenase reaction cycle, has been studied for its ability to reduce carbon-halogen bonds under anaerobic conditions. The reductive reactions functioned with NADH and the physiological electron-transfer proteins or by using artificial electron donors to reduce cytochrome P450CAM. Halogenated methane and ethane substrates were transformed by a two-electron reduction and subsequent protonation, beta-elimination, or alpha-elimination to yield alkanes, alkene, or carbene-derived products, respectively. Halogenated substrates bound to the camphor binding site as indicated by saturable changes in the Fe(III)-heme spin state upon substrate addition. Hexachloromethane was bound with a dissociation constant (KD) of 0.7 microM and caused > 95% shift from low- to high spin iron. Ethanes bearing fewer chlorine substituents were bound with increasing dissociation constants and gave lesser degrees of iron spin-state change. Camphor competitively inhibited hexachloroethane reduction with an inhibitor constant (KI) similar to the dissociation constant for camphor (KI = KD = 0.9 microM). Rate determinations with pentachloroethane indicated a 100-fold higher enzyme V/K compared to the second-order rate constant for hematin free in solution. These studies on substrate binding and catalysis will help reveal how biological systems enzymatically reduce carbon-halogen bonds in the environment. PMID- 8369307 TI - Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. AB - A detailed study of the kinetics of iron(II) oxidation by molecular oxygen in natural and recombinant human apoferritins has been carried out using electrode oximetry to better understand the ferroxidase activity of the protein shell. A comparative study of recombinant L-chain ferritin (rLF), recombinant H-chain ferritin (rHF), and variants has shown that (1) rLF lacks a ferroxidase activity, confirming the results of previous studies; (2) the ferroxidase site of rHF involves Glu-62 and His-65, presumably as Fe2+ ligands, since mutation of these residues abolishes most of the oxidase activity, in agreement with previous studies; and (3) mutation of both the putative ferroxidase and nucleation site ligands in rHF renders the protein totally incapable of catalyzing the oxidation of Fe2+ whereas mutation of nucleation site ligands alone (Glu-61, Glu-64, and Glu-67) decreases the activity only slightly. Analysis of the kinetics of rHF and natural human liver ferritin (HLF) (4% H-chain, 96% L-chain) gave the following apparent parameters at pH 7: Km,O2 = 6 +/- 2 microM, Km,Fe = 80 +/- 10 microM, and kcat = 201 +/- 14 min-1 for rHF and Km,O2 = 60 +/- 12 microM, Km,Fe = 50 +/- 10 microM, and kcat = 31.2 +/- 0.6 min-1 for HLF. Furthermore, Zn2+ was shown to be a noncompetitive inhibitor of Fe2+ oxidation in rHF but a mixed inhibitor in HLF. These different forms of Zn2+ inhibition in the two proteins and the higher activity of HLF than expected, based on its H-chain composition as well as differences in their enzyme kinetic parameters, suggest that H- and L-chains cooperate in modulating the ferroxidase activity of the apoferritin even though the L-subunit lacks a ferroxidase site itself. PMID- 8369309 TI - Generation, oxidation by the oxidized form of the tyrosine of polypeptide D2, and possible electronic configuration of the redox states S0, S-1, and S-2 of the water oxidase in isolated spinach thylakoids. AB - Suitable treatment of thylakoids with hydrazine permits a high population of the redox states S0, S-1, and S-2 in the water oxidase. Experiments performed with dark-adapted samples enriched either in the oxidized or reduced form of the redox active tyrosine, YD, of polypeptide D2 reveal that YoxD is a unique endogenous oxidant within the PS II complex which causes a one-electron abstraction from the water oxidase in states S0, S-1, and S-2, respectively. A kinetic analysis of the period four oscillation of oxygen yield induced by a train of short flashes in dark-adapted samples permits the determination of the rate constants of electron abstraction from the reduced water oxidase by YoxD. A value of 9 x 10(-4) s-1 was found for the oxidation of S0 and S-2, while S-1 becomes oxidized with a rate constant of 4 x 10(-4) s-1 at 20 degrees C and pH 7.2. The redox state S0 generated either from S1 via the three-flash-induced oxidative pathway through S4 or from a one-flash oxidation of the S-1 state obtained by S1 reduction with NH2NH2 exhibits the same kinetics as S0 oxidation by YoxD. On the basis of these findings and data taken from the literature, the electronic configuration of the manganese atoms in the tetranuclear cluster is discussed. It is assumed that the dimer model of two binuclear manganese groups within the tetranuclear cluster is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369308 TI - Evidence for the structure of the active site heme P460 in hydroxylamine oxidoreductase of Nitrosomonas. AB - Hydroxylamine oxidoreductase (HAO) is responsible for the oxidation of hydroxylamine to nitrite in nitrification by Nitrosomonas europaea. It has an alpha n subunit structure and eight covalently bound hemes per subunit. Seven of these have visible spectra indistinguishable from heme c. The eighth, designated as P460, has unusual visible spectroscopic features in the enzyme and in a heme containing proteolytic fragment. Its structure has not been previously determined. Enzymatic digestions of HAO were performed, and various proteolytic fragments were purified. Mass spectrometry confirmed the presence of authentic heme c in some fragments, that is, iron protoporphyrin IX cross-linked by two thioether bonds to cysteine residues. It was possible to detect the presence of the P460 pigment in some fragments, based upon the sensitivity of this pigment to treatment of the holoenzyme with hydrogen peroxide. A proteolytic fragment produced by sequential digestion with trypsin and pronase was shown to contain heme c and a hydrogen peroxide-sensitive heme with an unusual visible spectrum. This fragment contained two covalently cross-linked peptides. Mass spectrometry and NMR indicated that the P460 heme was iron protoporphyrin IX covalently bonded by two thioether bridges to peptide, but in addition there was a new, third covalent bond between a meso heme carbon and an aromatic ring carbon on a tyrosyl residue. The new covalent bond has been tentatively assigned to the C2 carbon of the tyrosyl ring and the 5-meso heme carbon (IUPAC-IUB tetrapyrrole nomenclature), although this location requires further proof. PMID- 8369310 TI - Calorimetric studies of the binding of ferric ions to human serum transferrin. AB - The binding of ferric ions, chelated with nitrilotriacetate, to human serum transferrin (hTF) has been studied using ultrasensitive titration calorimetry. Studies were done in both the presence and the absence of the synergistic bicarbonate anion. It was found that the C-site of hTF is capable of weakly binding bicarbonate (K of 250 M-1, delta H of -8 kcal) at the binding site even before ferric ion is added, although this does not happen to the same extent at the N-site. When preinsertion of the bicarbonate ion occurs, then ferric ion can subsequently bind very quickly to the C-site. Although the chelated ferric ion can bind weakly to the N-site in a fast reaction, the insertion of the bicarbonate ion occurs subsequently in a slow endothermic reaction. Binding of ferric ion to both sites is quickly reversible in the absence of bicarbonate but becomes kinetically controlled for long periods of time once bicarbonate has inserted into the metal-binding site due to the long time required for release of ferric ion. Estimates of the heats of binding to each site, apparent binding constants, and heat capacities of binding are made for different sets of solution conditions. Results from this study are compared to earlier results with ovotransferrin (Lin, L.-N., Mason, A. B., Woodworth, R. C., & Brandts, J. F. (1991) Biochemistry 30, 11660-11669), with major differences and some similarities noted. PMID- 8369311 TI - Nuclear magnetic resonance relaxation of glycogen H1 in solution. AB - The NMR relaxation properties of the H1 proton of oyster glycogen in D2O and H2O solutions have been studied using nonselective, semiselective, and selective inversion recovery and Hahn spin-echo pulse sequences. The data were analyzed in terms of an isotropic, rigid-rotor dipole-dipole model including cross relaxation. At 8.4 T in D2O, p = 5.4 +/- 0.4 s-1 and sigma = -4.5 +/- 0.4 s-1. The large, negative sigma value is consistent with strong cross-relaxation and a long correlation time. The relaxation data can be explained by a single correlation time, tau c = 2.7 x 10(-9) s, indicating significant internal mobility. With this value of tau c, and assuming that the structure of the glucose moieties was the same as in alpha-D-glucose crystals, the dipole sum contributing to T1 relaxation was calculated. The intra-ring relaxation was dominated by dipole fields from the H2 proton, but these only accounted for approximately 18% of the total relaxation. Most of the relaxation comes from inter-glucose relaxation. From modeling, this is dominated by the H4' across the alpha-1,4-glycosidic bond. The H1 longitudinal relaxation rates were significantly enhanced in H2O compared with D2O. This enhancement is not due to direct dipolar interaction between H1 and bulk water. Transverse relaxation rates were not significantly enhanced in H2O. PMID- 8369312 TI - Transfer nuclear Overhauser effect study of the conformation of oxytocin bound to bovine neurophysin I. AB - This study reports the structure of the peptide hormone oxytocin bound to its carrier protein, neurophysin I, obtained by nuclear magnetic resonance techniques. At the pH value of 2.1 in our experiments, the ligand is in fast exchange with its carrier protein, allowing the use of transfer-NOE methods. The number of distance constraints for the peptide being limited, considerable attention has been paid to an accurate distance determination. The resulting accurate distance limits were used as input for a distance geometry calculation followed by a restrained molecular dynamics run. Convergence to a well-defined family of structures for oxytocin in its bound state was reached. Both the backbone and the side-chain conformations differ between the bound form and the crystal structure of free oxytocin [Wood, S. P., et al. (1986) Science 232, 633]. These differences, as well as other structural features of the bound form, are discussed in terms of interactions made with the carrier protein. Transfer-NOE experiments at low peptide protein ratios provide direct experimental evidence for contacts between the oxytocin Tyr2 residue and an aromatic residue of neurophysin. The resonance assignments of the aromatic groups [Whittaker, B. A., et al. (1985) Biochemistry 24, 2782] together with the recently published X-ray structure of the neurophysin II protein complexed with a dipeptide [Chen et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4240] allow us to assign the aromatic signal on the protein to the neurophysin Phe22 residue. PMID- 8369313 TI - Efficiency of N-linked core glycosylation at asparagine-319 of rabies virus glycoprotein is altered by deletions C-terminal to the glycosylation sequon. AB - In N-linked core glycosylation, the oligosaccharide Glc3Man9GlcNAc2 is transferred to the tripeptide sequon Asn-X-Ser/Thr. However, this process must be regulated by additional protein signals, since many sequons are either poorly glycosylated or not glycosylated at all. Since N-linked glycosylation can influence protein structure and function, understanding these signals is essential for the design and expression of recombinant glycoproteins. Core glycosylation usually occurs cotranslationally in the rough endoplasmic reticulum (RER) during translocation of nascent proteins. Since only regions of a protein immediately near to a sequon or N-terminal to it are thought to be in the RER when core glycosylation occurs, most models predict that regions C-terminal to the sequon do not influence this process. We tested whether regions C-terminal to a sequon can influence its core glycosylation. Full-length (505 amino acid) rabies virus glycoprotein (RGP) mutants, each containing only one of the three sequons normally present in RGP, were used for these studies. Using a cell-free system, the core glycosylation efficiency at each sequon was determined. Termination codons were then introduced into these mutants at defined sites to produce C-terminal truncations, and the effect of each of these truncations on the core glycosylation efficiency at each sequon was assessed. While deletion of the C-terminal transmembrane and cytoplasmic domains did not affect core glycosylation, more extensive C-terminal deletions did result in altered core glycosylation in a site-specific fashion. Specifically, C-terminal truncations resulting in proteins containing 386 or 344 amino acids decreased the efficiency of core glycosylation at Asn319. This demonstrates that core glycosylation efficiency can be influenced by the presence or absence of regions in a protein more than 68 amino acids C-terminal to a specific glycosylation site. PMID- 8369314 TI - Expression and identification of p90 as the murine mitochondrial glycerol-3 phosphate acyltransferase. AB - Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the initial and committed step in glycerolipid biosynthesis. Mitochondrial GPAT, unlike the microsomal isozyme, prefers saturated fatty acids as a substrate. We have recently reported cloning of a cDNA to an unidentified 6.8-kb mRNA by a differential hybridization. The mRNA contains an open reading frame of 827 amino acids (p90) with 30% sequence homology in a 300 amino acid stretch to Escherichia coli GPAT. The 6.8 kb mRNA was induced dramatically when fasted mice were refed a high-carbohydrate diet. Here, we have expressed the open reading frame as trpE fusion proteins and used them to generate antibodies. The antibodies recognized a polypeptide of 90 kDa (p90) when the 6.8-kb cDNA sequence was used for in vitro transcription and translation. By Western blot analysis using these antibodies, we detected p90 in mitochondrial fractions of liver, and the p90 level was increased by refeeding. The increase in the p90 level correlated with the increase in mitochondrial GPAT activity. Moreover, p90 was not detectable in 3T3-L1 preadipocytes but markedly increased during adipose conversion. This increase was consistent with the 11 fold increase we observed in N-ethylmaleimide (NEM)-resistant mitochondrial GPAT activity during adipocyte differentiation. In addition, we have expressed p90 in CHO cells by stable transfection. The transfected genes in both correct and reverse orientations produced distinct 3.9-kb transcripts owing to the truncation of a part of the noncoding regions of the endogenous 6.8-kb mRNA before insertion into the pMSXND vector. The transfected CHO cells were treated with 2 aminopurine, an agent that increases expression of exogenous genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369316 TI - Hepatic lipase acylates dolichol in the presence of a plasma cofactor in vitro. AB - Phosphatidylethanolamine:dolichol acyltransferase (PEDAT), an enzyme previously partially purified and characterized in rat liver [Sindelar, P., Chojnacki, T., & Valtersson, C. (1992) J. Biol. Chem. 267, 20594-20599], is here purified to homogeneity from a heparin perfusate of rat liver and is shown to be identical to hepatic lipase. However, in contrast to triglyceride hydrolysis by hepatic lipase, the PEDAT activity is strongly dependent on a heat-stable plasma cofactor. This cofactor stimulates the activity up to 15-fold and shifts the pH optimum for the reaction from 8.5 to 7.5. Upon gel filtration on Bio-Gel A-1.5, the factor is heterogeneously distributed, with a major peak at 220 kDa. The dolichol-acylating activity can also be detected in rat adrenals and ovaries, and evidence is presented that the PEDAT assay shows a higher degree of specificity for hepatic lipase than the standard assay with triolein-gum arabic emulsion in 1 M NaCl. PMID- 8369315 TI - A prenylated protein-specific endoprotease in rat liver microsomes that produces a carboxyl-terminal tripeptide. AB - The maturation of proteins that contain the C-terminal sequence Cys-Ali-Ali-Xaa (where Ali is usually an aliphatic amino acid and Xaa is a number of different amino acids) involves the attachment of a farnesyl or geranylgeranyl group to the cysteine residue, proteolytic removal of the C-terminal three amino acids, and methylation of the prenylated cysteine alpha-carboxyl group. Two prenylated and radiolabeled peptides were prepared in order to detect the proteolysis step(s) in a cell-free system and to determine the reaction products. These peptides are ECB NPFRQRRFFC(S-geranylgeranyl)AI[3H]L and ECB-C(S-farnesyl)VI[3H]S (ECB is an extended-chain biotin group) which are patterned after the C-termini of geranylgeranylated and farnesylated G protein gamma-subunits. Incubation of these peptides with rat liver microsomes, but not cytosol, results in the production of radiolabeled dipeptides (I[3H]L and I[3H]S) and tripeptides (AI[3H]L and VI[3H]S) as the major products and smaller amounts of amino acids ([3H]L and [3H]S). A multitude of independent experiments shows that the dipeptides are produced from the tripeptides by secondary proteolysis. Although a portion of the [3H]S produced comes directly from ECB-C(S-farnesyl)VI[3H]S, the KM of > 30 microM for this reaction is significantly higher than the KM of 1.1 microM for the production of VI[3H]S from the farnesylated peptide. This suggests that the carboxypeptidase is not part of the pathway for the maturation of prenylated proteins. Nonprenylated peptides at concentrations of 10-100-fold higher than those of the prenylated substrates did not reduce the amount of tripeptide produced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369317 TI - The Registry of the International Society for Heart and Lung Transplantation: tenth official report--1993. PMID- 8369318 TI - Pretransplantation risk factors for death after heart transplantation: a multiinstitutional study. The Transplant Cardiologists Research Database Group. AB - Risk factors for death after heart transplantation were identified by analyzing the total primary heart transplantation experience (n = 911) among 25 institutions from January 1, 1990, through June 30, 1991. Overall actuarial survival was 93% at 1 month and 84% at 12 months. The hazard function for death was highest early after heart transplantation and fell rapidly over the first 6 months, with a gradually declining hazard thereafter. The two most common causes of death were infection (n = 29) and early graft failure (n = 28), accounting for 45% of the overall deaths. By multivariable analysis, risk factors for death during the study period included very young recipient age (p = 0.004), advanced age (p = 0.009), ventilator support at time of transplantation (p = 0.09), abnormal renal function (p = 0.1), lower pretransplantation cardiac output (p = 0.009), higher pulmonary vascular resistance in children (p = 0.006), longer donor ischemic time (p = 0.001), older donor age (p = 0.001), and donor and recipient not both blood type O (p = 0.009). The recipient age effect was greatest in patients under 5 years of age (1-year survival rate 68% versus 85% for all others, p = 0.002). Patients aged 60 years and older had a 1-year survival rate of 81%. Patients who were ventilator dependent at transplantation fared especially poorly, with a 3-month survival rate of 65%. Transplantation of a blood group O heart into a non-O recipient had a somewhat lower 1-year survival rate than did blood group O into an O recipient (82% versus 88%, p = 0.06). The adverse effect of a longer ischemic time was most notable after 4 hours (1-month survival rate 71% for more than 4 hours versus 85% for less than 4 hours, p = 0.0003). Inference: These multiinstitutional-derived risk factors for early-term death after heart transplantation may help improve patient and donor selection and focus further scientific investigations to increase the safety of heart transplantation. PMID- 8369319 TI - Spectrum of humoral rejection after pediatric heart transplantation. AB - The deposition of immunoglobulin and complement 3 in the coronary microvasculature (humoral rejection) has been associated with poor outcome after heart transplantation. The purpose of this study is to relate the incidence of immunoglobulin and complement 3 myocardial deposition to the clinical course of pediatric heart transplant patients. One hundred thirty-one biopsy specimens from 30 patients, whose mean age at transplantation was 4.9 years (range, 2 days to 17 years), were processed for light microscopy and immunofluorescence. The mean follow-up was 25 months (range, 6 to 63 months). All patients underwent annual selective coronary artery angiography. No cellular or humoral rejection was seen in 97 biopsy specimens. Humoral rejection without cellular infiltrate was found in eight biopsy specimens from four patients (13%). Of 19 grade 1A, B (mild) biopsy specimens, 17 showed only cellular rejection, and two showed a mixed pattern of cellular and humoral rejection. Of six grade 2,3 (moderate) biopsy specimens, four showed only cellular rejection, and two showed a mixed pattern. The only grade 4 (severe) biopsy specimen revealed a mixed pattern. Three patients have had persistent immunoglobulin M and complement 3 deposits. One of these had angiographic evidence of accelerated graft coronary artery disease 2 years after transplantation, which was later confirmed at autopsy. Coronary artery disease has not been detected by serial angiography at 1 year (28 patients), 2 years (18 patients), 3 years (15 patients), 4 years (five patients), and 5 years (one patient). Humorally mediated rejection occurs with and without cellular rejection after pediatric heart transplantation. Humoral rejection may persist after treatment and resolution of severe cellular rejection episodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369320 TI - The impact of steroid withdrawal on the development of lipid abnormalities and obesity in heart transplant recipients. AB - Hyperlipidemia and obesity are common problems after heart transplantation, which may increase the risk of chronic graft atherosclerosis. The intent of this study was to (1) determine the impact of a history of hyperlipidemia on the occurrence of lipid abnormalities after transplantation, (2) compare lipid profiles of those patients being treated with triple-drug immunosuppression versus those patients weaned from prednisone therapy, and (3) identify any factors that would predict which patients are at highest risk for the development of hyperlipidemia after transplantation. Of 89 patients who lived for more than 12 months, 35 patients had a history of hyperlipidemia before heart transplantation (cholesterol level of more than 240 mg/dl; low-density lipoprotein cholesterol level of more than 160 mg/dl). The most dramatic rise in cholesterol level was observed in patients with no history of hyperlipidemia who were treated with triple-drug immunosuppression, in whom a 64% increase occurred versus a 24% increase in patients receiving steroid-free immunosuppression (p < 0.001). In patients with a history of hyperlipidemia, cholesterol level increased by 20% with triple-drug immunosuppression versus 14% with steroid-free immunosuppression (p = 0.613); however, 83% of the patients in the triple-drug group and 92% in the steroid-free group had elevated cholesterol levels. Multiple regression analysis revealed that significant independent and additive (p < 0.00001) contributions with respect to percent change in cholesterol level were evident for (1) a negative history of hyperlipidemia (p = 0.005), (2) triple-drug immunosuppression (p = 0.0021), and (3) female sex (p = 0.0113). A negative history of hyperlipidemia was predictive of the percent change in low-density lipoprotein cholesterol level (p = 0.0049), and triple-drug immunosuppression administration predicted the percent change in high-density lipoprotein cholesterol (p = 0.0119). Patients with a positive history of hyperlipidemia had higher lipid values at 12 and 24 months after transplantation; however, patients with no previous history of hyperlipidemia experienced the greatest percent change in both cholesterol and low-density lipoprotein levels. Patients receiving prednisone therapy gained more weight (9.0 +/- 7.0 kg) as compared with those patients tapered from prednisone therapy (5.9 +/- 8.6 kg); however, neither the increase in actual weight (p = 0.120) nor the increase in percent ideal body weight (14% +/- 11% versus 9% +/- 13%, respectively) were significant (p = 0.133). This study identified that postoperative weight gain is best predicted by premorbid habitus, rather than the type of immunosuppression used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8369321 TI - OKT3 treatment of cardiac allograft rejection. AB - Since the initial report of the murine monoclonal antibody OKT3 for acute kidney rejection, a significant body of information has been collected regarding the efficacy of OKT3 in reversing acute allograft rejections in kidney, liver, and heart transplant recipients. The use of OKT3 therapy for the reversal of cardiac allograft rejection in patients in whom other therapeutic alternatives have failed or are contraindicated is described. Treatment with OKT3 reversed acute heart rejection in 102 of 113 patients (90%). Complete reversal was achieved in 63 patients, and partial reversal in 39 patients. At 2 years, graft and patient survival rate was 77% and 65%, respectively. No significant differences were noted in reversal rate and in 12-month graft and patient survival rates between those patients experiencing one rejection episode and those patients experiencing two or more rejection episodes. Comparable reversal rates and graft and patient survival rates were achieved in patients whether OKT3 was administered as the primary rejection therapy or as rescue therapy. Adverse events were common in the first 2 days of therapy, but they were well tolerated in most patients. Infectious complications occurred in 49% of patients in whom most infections were not serious. On the basis of this experience, OKT3 appears highly effective in reversing acute cardiac allograft rejection. PMID- 8369322 TI - Aspergillosis with Aspergillus osteomyelitis and diskitis after heart transplantation: surgical and medical management. AB - This is the report of a 49-year-old man, who could be cured of aspergillosis with Aspergillus osteomyelitis and diskitis of the lumbar spine by medical and surgical therapy after heart retransplantation. Aspergillus osteomyelitis and diskitis is a rare complication of invasive aspergillosis. Lumbar involvement is the main manifestation, followed by rare locations in the tibia, ribs, wrist, sternum, pelvis, and knee. It is nearly always secondary to pulmonary aspergillosis, which occurs in about 6% to 14% of patients after heart transplantation. For treatment, a combined surgical and medical approach is recommended, which enables quick pain relief for the patient and histologic and microbiologic diagnosis and stabilization of the spine. Because of definitive cure of osteomyelitis cannot be guaranteed by removal of the abscess, medical therapy after surgery is necessary for years. PMID- 8369323 TI - Noninvasive assessment of the pulmonary artery pressure response to exercise after uncomplicated heart transplantation. AB - The pulmonary artery pressure response to exercise has been used as an index of cardiac reserve and frequently mirrors diastolic conditions. To define this response after orthotopic heart transplantation, we exercised 27 subjects on supine bicycle ergonometers. Stroke volume and pulmonary artery pressure were monitored with contrast-enhanced Doppler imaging. Study patients had undergone orthotopic heart transplantation. Seventeen patients were screened, and eight were subsequently determined by endomyocardial biopsy to be histologically free of acute cardiac allograft rejection. A control population of nonconditioned normal volunteers was also evaluated (heart transplant patients: n = 8, age = 45.7 +/- 7.3 years, seven men; normals volunteers: n = 10, age = 49.4 +/- 12.8 years, nine men; P = NS). Total exercise time and peak heart rate were reduced in heart transplant patients: 7.6 +/- 2.5 minutes, 123 +/- 4 beats/min versus normal volunteers: 16.2 +/- 4.5 minutes, 134 +/- 4 beats/min (P < 0.05). Change in stroke volume from baseline to peak exercise was greater in heart transplant patients: 29.9 +/- 4.6 ml versus normal volunteers: 3.9 +/- 5.7 ml (P < 0.01). No difference was observed in the pulmonary artery pressure response to exercise. In patients with uncomplicated heart transplantation a reduction in exercise capacity is shown; however, the pulmonary artery pressure response to exercise is comparable to normal subjects. A blunted heart rate response is observed, which is partially compensated by increases in stroke volume. These findings suggest that cardiac diastolic function is preserved and that denervation of the heart accounts for impaired exercise tolerance. PMID- 8369324 TI - Importance of substrate enhancement for long-term heart preservation. AB - These experiments tested the hypothesis that addition of pyruvate to a preservation medium would improve postpreservation cardiac function as quantified in an isolated working heart model after heterotopic transplantation. Four groups of rabbit hearts were studied (n = 5 per group): fresh controls, fresh hearts perfused as isolated working hearts; surgical controls, fresh hearts transplanted heterotopically and reperfused with blood for 75 minutes before being studied as isolated hearts; preserved without pyruvate, hearts perfusion-preserved with oxygenated extracellular-type crystalloid medium; preserved with pyruvate, same same as the group without pyruvate, but medium contained 20 mmol/L pyruvate. After preservation, the hearts in the two preserved groups were transplanted and studied as isolated hearts. Total ex vivo time for the preserved hearts was 24.5 +/- 0.2 hours. During preservation, glucose was not consumed by hearts in either preserved group. Pyruvate was used by the hearts to which it was provided (22.9 +/- 2.7 mumol pyruvate x hour-1 x gm dry weight-1). Performance of transplanted surgical control hearts was not significantly different from that of fresh controls. Function of the pyruvate-preserved hearts was similar to that of the fresh and surgical controls except that left ventricular peak systolic pressure and peak rate of pressure development were lower and that left ventricular end diastolic pressure was higher for the pyruvate-preserved hearts. The hearts preserved without pyruvate had significantly lower compliance and function compared to the other three groups, which was evident in all indexes of contractility and output. We conclude that hearts preserved with pyruvate containing crystalloid medium had better postpreservation, posttransplantation function than hearts preserved without pyruvate, although there was slight loss of compliance and decreased contractile function in the pyruvate-preserved hearts compared to controls. PMID- 8369325 TI - One-hour exposure to University of Wisconsin solution does not impair endothelium dependent relaxation or damage vascular smooth muscle of epicardial coronary arteries. AB - To determine whether University of Wisconsin solution impairs production of endothelium-derived relaxing factor or damages vascular smooth muscle function of epicardial coronary arteries, isolated segments of canine left circumflex coronary artery were exposed to either cold (7 degrees C) or normothermic (37 degrees C) University of Wisconsin solution or to cold (30 degrees C) or normothermic (37 degrees C) physiologic salt solution in vitro for 60 minutes. After incubation with the solutions, the vascular segments were studied in vitro in organ chambers. Exposure to cold or to normothermic University of Wisconsin solution did not alter endothelium-dependent relaxation (either maximal relaxation or ED50) of the segments in response to adenosine diphosphate or acetylcholine (10(-9) to 10(-4) mol/L). Also, contraction of the segments in response to potassium ions (voltage-dependent) or prostaglandin F2 alpha (receptor-dependent) and relaxation in response to isoproterenol (cyclic AMP mediated) or sodium nitroprusside (cyclic GMP-mediated) were unaltered after exposure to cold University of Wisconsin solution. Direct exposure to normothermic University of Wisconsin solution induced transient vasoconstriction in segments with or without endothelium. Thus University of Wisconsin solution does not irreversibly impair release of endothelium-derived relaxing factor or alter function of vascular smooth muscle in epicardial coronary arteries. PMID- 8369326 TI - Cyclosporine increases the intracellular free calcium concentration in electrically paced isolated rat cardiomyocytes. AB - The effect of cyclosporine on the mean cytoplasmic free calcium concentration in electrically paced single cardiomyocytes from adult rats was studied. Cardiac myocytes were paced by electrical field stimulation with either 2 or 3 Hz in the presence of 5 micrograms/ml cyclosporine or the solvent cremophor. Exposure to cyclosporine during 40 minutes of electrical pacing caused irreversible hypercontracture in most cells, only 22.1% +/- 1.2% (mean +/- SEM) remained rod shaped versus 64.1% +/- 3.2% in the solvent (p = 0.01). The cytoplasmic free calcium concentration was measured by means of digital image processing of fura-2 fluorescence. Electrical field stimulation increased the cytoplasmic free calcium from 69.7 +/- 5.4 to 124.9 +/- 24.5 nmol/L Ca2+ in the presence of the solvent and from 84.2 +/- 25.4 to 250.1 +/- 55.9 nmol/L in the presence of cyclosporine (p = 0.036 versus solvent). The data provide direct evidence that cyclosporine enhances the cytoplasmic free calcium concentration in single paced rat cardiomyocytes. These findings may be of importance in the consideration of a possible cardiotoxicity of cyclosporine. PMID- 8369327 TI - Chylothorax: report of a case complicating orthotopic heart transplantation. AB - We describe a case of a chylothorax that occurred in a 62-year-old man after orthotopic heart transplantation. Injury to collateral lymphatics in the anterior mediastinal or thymic areas was the probable cause of the chylous fistula. Excessive chyle drainage causes loss of large amounts of fat, protein, electrolytes, and lymphocytes. These losses further compromise the nutritional and immunologic status of the transplant patient. Conservative therapy with chest tube drainage and a strict medium-chain triglyceride diet allowed the chylous fistula to spontaneously close without the need for surgical intervention. PMID- 8369328 TI - Prognosis of patients with cystic fibrosis awaiting heart and lung transplantation. AB - Heart-lung transplantation is a successful treatment for patients with cystic fibrosis and chronic respiratory failure. Patients are assessed for surgery when life expectancy is deemed short. This study assesses the ability of measurements of pulmonary function, blood gas levels, and nutritional status to predict survival of patients awaiting heart-lung transplantation and to assess the effect of heart-lung transplantation on survival. Sixty-seven patients with cystic fibrosis were accepted for heart-lung transplantation from 1985 through 1990. Each patient underwent tests of pulmonary function, exercise tolerance, blood-gas levels, and nutritional status. Cox regression was used to analyze the prognostic value of these data. Of the 67 patients accepted for heart-lung transplantation, organs became available for 30; 24 patients died waiting, and 13 patients were on the list December 31, 1990. Eight patients died after transplantation. Patients with above-average forced expiratory volume in 1 second (FEV1) (median, 17% predicted) at assessment were half as likely to die waiting (relative risk, 0.47; 95% confidence interval, 0.23 to 0.97) as patients with below-average FEV1. The relative risk of death for patients on the waiting list was 1.44 (95% confidence interval, 1.17 to 1.77) for each increment in PCO2 of 1 kPa. No effect of nutritional status on waiting list death was found, but seven of eight patients who died after heart-lung transplantation were below 80% predicted weight for height. Using a time-dependent analysis, heart-lung transplantation almost halved the risk of death (relative risk, 0.57; 95% confidence interval, 0.22 to 1.48). Postoperative actuarial survival was 79% (95% confidence interval, 63% to 95%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369329 TI - The diagnosis of obliterative bronchiolitis after heart-lung and lung transplantation: low yield of transbronchial lung biopsy. AB - Obliterative bronchiolitis is the most significant long-term complication of lung and heart-lung transplantation characterized by the rapid development of obstructive airway disease. It is thought to be a manifestation of chronic rejection and has been treated, with limited success, with augmentation of immunosuppression. Early detection of obliterative bronchiolitis and prompt initiation of therapy may result in an improved outcome. The role of transbronchial biopsy has been reported in the diagnosis of acute rejection and infection but not for obliterative bronchiolitis. To study this problem we retrospectively reviewed the transbronchial biopsy results of patients with advanced clinical obliterative bronchiolitis, as defined physiologically. Between January 1, 1988, and December 31, 1991, 46 "sets" of adequate transbronchial biopsy specimens were obtained from 16 patients (15 heart-lung recipients and one double lung recipient). Seven sets of transbronchial biopsy specimens (15.2%) showed obliterative bronchiolitis by pathologic study. In four patients with severe clinical obliterative bronchiolitis, only one transbronchial biopsy specimen of seven (14.3%) showed obliterative bronchiolitis. The pathologic diagnosis of obliterative bronchiolitis was confirmed in three of these patients at the time of autopsy or retransplantation. Twelve patients were still alive at the end of the study period, and all experienced further deterioration of lung function typical for obliterative bronchiolitis. We conclude that the sensitivity of transbronchial biopsy for obliterative bronchiolitis is poor. Possible explanations for these results are explored. PMID- 8369330 TI - Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation. AB - Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation. PMID- 8369331 TI - Transesophageal echocardiographic assessment of pulmonary venous flow after single lung transplantation. AB - Transesophageal echocardiography was used to evaluate pulmonary venous flow velocity and pulmonary venous diameter of both the transplanted and native lungs in six single lung transplant recipients. Mean pulmonary venous velocity (50 +/- 10 versus 27 +/- 8 cm/sec) and pulmonary venous diameter (1.39 +/- 0.16 versus 0.98 +/- 0.18 cm) were significantly greater in the transplanted lung than in the native contralateral lung. An index of allograft perfusion, QD-transesophageal echocardiography (pulmonary venous velocity x pulmonary venous diameter), correlated highly with previously measured technetium 99m-labeled macroaggregated albumin quantitative lung perfusion studies (r = 0.94). A pressure gradient in pulmonary venous flow velocity across the left atrial anastomosis was detected in two patients (8 and 12 mm Hg). Analysis of previous resting supine and upright incremental hemodynamic exercise testing showed no significant differences in these two patients with respect to maximum oxygen uptake, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index, or pressure-flow relationships. Therefore these left atrial anastomotic gradients did not appear to adversely affect the pulmonary vascular response to incremental exercise. Transesophageal echocardiography may be an invaluable technique in the expedient evaluation of cardiac function and allograft perfusion after lung transplantation. PMID- 8369332 TI - Should alpha 1-antitrypsin-deficient patients with emphysema continue to receive alpha 1-antitrypsin after lung transplantation? PMID- 8369333 TI - Ventilatory problems observed after single lung transplantation in emphysema. PMID- 8369334 TI - Picosecond energy transfer and trapping kinetics in living cells of the green bacterium Chloroflexus aurantiacus. AB - The excitation energy transfer and trapping processes in intact cells of Chloroflexus aurantiacus were studied by picosecond time-resolved fluorescence spectroscopy. The fluorescence decay kinetics is investigated over the near infrared emission range between 730 nm and 920 nm using various excitation wavelengths and excitation intensities. The data were analyzed by global decay analysis and are presented as decay-associated spectra (DAS). The specific dependence of the decay kinetics on the excitation wavelength and on the photochemical redox state of the reaction center (RC) allows the identification of the energy transfer and trapping components. The DAS provide evidence for two chlorosomal energy transfer processes. The first one occurs between the chlorosomal bacteriochlorophyll (BChl)-c and the BChl-a792 complex (B792) in the chlorosomal baseplate with an equilibration time constant of 15-16 ps, while the second one occurs from the B792 pigments to the BChl-a806 pigments in the B806 866 complex with a time constant of 35-40 ps. The overall energy trapping process in whole cells is mainly determined by the kinetics of the primary charge separation process in the RCs. With open RCs (QA oxidized) the trapping time constant is 70-90 ps, while the trapping process with closed RCs (QA reduced) takes as long as 180-200 ps. The results on whole cells reported here are interpreted in conjunction with those reported earlier for the various isolated complexes, i.e., two different chlorosome preparations (Holzwarth, A.R., Muller, M.G. and Griebenow, K. (1990) J. Photochem. Photobiol. B 5, 457-465), the B806 866 complex (Griebenow, K., Muller, M.G. and Holzwarth, A.R. (1991) Biochim. Biophys. Acta 1059, 226-232) and isolated reaction centers (Muller, M.G., Griebenow, K. and Holzwarth, A.R. (1991) Biochim. Biophys. Acta 1098, 1-12). Based on these data, a unified and self-consistent scheme for the primary processes in the whole photosynthetic system of C. aurantiacus is presented. The BChl antenna pigment groups are arranged to form a linear energy transfer cascade with four energy transfer steps from shorter-wavelength- to longer-wavelength absorbing antenna pools. The overall fluorescence decay kinetics of the photosynthetic system of C. aurantiacus turns out to be 'trap-limited' by the reaction center rather than 'diffusion-limited' by the energy transfer processes. PMID- 8369335 TI - From uni-site to multi-site ATP synthesis in thylakoid membranes. AB - The membrane-bound H(+)-ATPase from chloroplasts, CF0F1, was brought into the active, reduced state by illumination in the presence of thioredoxin and dithiothreitol. The endogenous nucleotides were removed by a washing procedure so that the active, reduced enzyme contained one tightly bound ATP per CF0F1. When [14C]ADP was added in substoichiometric amounts during continuous illumination, ADP was bound to the enzyme, phosphorylated and released as [14C]ATP, i.e., the tightly bound ATP was not involved in the catalytic turnover ('uni-site ATP synthesis'). The rate constant for ADP binding was k = (2.0 +/- 0.5) x 10(6) M-1 s-1. The rate of ATP synthesis was measured as a function of the ADP concentration from 8 nM up to 1 mM in the presence of 2 mM phosphate during continuous illumination. A linear increase of the rate was observed up to 100 nM. Above this concentration a supralinear increase was found, indicating the occupation of a second ADP-binding site. A plateau was reached between 1.5 microM and 2.3 microM ADP with a rate of vpl = 3.7 s-1. The half-maximal rate from this plateau was observed at 780 nM. Above 2.3 microM ADP up to 1 mM ADP the data were described by Michaelis-Menten kinetics (vmax = 80 s-1; apparent KM = 32 microM). These results indicated the participation of at least two different ADP binding sites in ATP synthesis catalyzed by the membrane-bound CF0F1. PMID- 8369336 TI - Is cellobiose oxidase from Phanerochaete chrysosporium a one-electron reductase? AB - The heme domain of cellobiose oxidase (CBO) from Phanerochaete chrysosporium increases the rate of electron transfer to one-electron acceptors. This conclusion was drawn from comparisons of the rates of reduction of 3,5-t-butyl-o benzoquinone, triiodide ion, cytochrome c and ferricyanide by intact CBO, FAD fragment and CBO with the heme inactivated by cyanide. The oxidation of cellobiose produced hydrogen peroxide, but the enzyme disturbs peroxidase-based assays by reduction of the product or by direct interaction with the peroxidase. CBO can also degrade hydrogen peroxide in the presence of cellobiose. The 1,2,4,5 tetramethoxybenzene cation radical was rapidly reduced by CBO. PMID- 8369337 TI - Electrochromic responses of carotenoid absorbance bands in purified light harvesting complexes from Rhodobacter capsulatus reconstituted into liposomes. AB - Light-Harvesting Complexes I and II (LHI and LHII) were extracted from chromatophores of Rhodobacter capsulatus, purified in Triton X-100 and reconstituted into phospholipid vesicles. Application of membrane potentials (K+ diffusion potentials) to LHII proteoliposomes led to absorbance changes in the carotenoid bands which were spectrally similar to those in chromatophores. These (electrochromic) absorbance changes were linear with the applied membrane potential between -107 mV and +105 mV. The data were consistent with the existence of two forms of carotenoid in LHII. One form, comprising 2/3 of the total and with a long wavelength absorbance maximum at 510 nm, was not significantly affected by membrane potential. The other component, comprising 1/3 of the total and with a long wavelength absorbance maximum at 516.5 nm, was shifted by approx. 1.6 nm to the red by a membrane potential of 105 mV. Reduction of the B800 bacteriochlorophyll in LHII with NaBH4 before reconstitution did not affect the absorbance spectrum of the carotenoids and it did not affect their response to applied membrane potentials in proteoliposomes. Although the electrochromically-sensitive carotenoids might be associated with B800, interactions with the bacteriochlorophyll are perhaps not the cause of the polarisation of the carotenoid that is responsible for the linearity of the response. The carotenoids in reconstituted LHI complexes were not detectably electrochromic. The electrochromic absorbance changes of carotenoids in LHII could be useful for membrane potential measurement in liposomes containing ion translocating proteins. PMID- 8369338 TI - Electrochromic responses of bacteriochlorophyll absorbance bands in purified light-harvesting complexes of Rhodobacter capsulatus reconstituted into liposomes. AB - Purified light harvesting complexes I and II (LHI and LHII) from Rhodobacter capsulatus were purified and separately incorporated into liposomes. Electrochromic absorbance changes of bacteriochlorophyll bands in the proteoliposomes in response to K(+)-diffusion potentials were recorded. In LHII proteoliposomes the application of positive-inside potentials led to red shifts in the bacteriochlorophyll absorbance bands centered at 377, 801 and 858 nm. Negative-inside potentials caused blue shifts of these bands. Electrochromism of the 590 nm band was too small to detect. The band at 858 nm was considerably more electrochromic than that at 801 nm. Electrochromic absorbance changes measured at 865-850 nm were linear with the applied diffusion potential. In LHI proteoliposomes positive-inside diffusion potentials caused red shifts of the bands centred at 374 nm and 880 nm. At 880 nm the response was linear with the applied diffusion potential and was equivalent in amplitude to that of the 858 nm band in LHII proteoliposomes. If it is assumed that the permanent dipole moment differences between the ground state and excited state of B800, B850 and B870 are similar and that polarisability effects are negligible, it follows that (a) the plane of the bacteriochlorin ring of B850 is more perpendicular to the membrane plane than that of B800 and (b) the orientations of B850 and B870 relative to the membrane plane are similar. PMID- 8369339 TI - Analysis of chimeric spinach/cyanobacterial CP43 mutants of Synechocystis sp. PCC 6803: the chlorophyll-protein CP43 affects the water-splitting system of Photosystem II. AB - Mutants of the cyanobacterium Synechocystis sp. PCC 6803 have been generated in which parts of psbC (the gene encoding the Photosystem II chlorophyll-protein CP43) have been replaced with the homologous gene fragment from spinach. Upon the replacement of all but the 3' 84 bp of the cyanobacterial psbC gene with the homologous fragment from spinach, an obligate photoheterotrophic mutant was generated. Two photoautotrophic derivatives of this mutant were made reincorporating 3' cyanobacterial sequences back into the spinach psbC gene of the mutant. These two mutants are similar to each other, carrying a chimeric CP43 with the N-terminal half from spinach. These mutants are photosynthetically active at a rate of about half that of wild type, which correlates with a decreased Photosystem II/chlorophyll ratio in these mutants. Thylakoids from the chimeric mutants contain a CP43 protein which migrates slightly more slowly on SDS-polyacrylmide gels than the native Synechocystis CP43. Interestingly, these mutants show significant shifts in thermoluminescence peaks, reflecting altered thermodynamic properties of the back reaction between the acceptor side and the water-splitting system. On the basis of the oscillations of these shifts with number of flashes, we conclude that S2 is stabilized and S3 is destabilized in these mutants. This represents evidence for an involvement of CP43 in events associated with water splitting. PMID- 8369340 TI - Intimate relationships of the large and the small subunits of all nickel hydrogenases with two nuclear-encoded subunits of mitochondrial NADH: ubiquinone oxidoreductase. AB - The sequence pattern CxxCxnGxCxxxGxmGCPP, thus far found in the small subunits from 21 different nickel hydrogenases, appears also to be present in the PSST polypeptide from NADH:ubiquinone oxidoreductase (Complex I) of beef-heart mitochondria. There is only one difference: the first cysteine residue is a leucine in the PSST subunit. The large nickel-binding subunit of nickel hydrogenases shows a surprising homology with the 49 kDa subunit of mitochondrial Complex I. PMID- 8369341 TI - Activation and inhibition of mitochondrial transhydrogenase by metal ions. AB - Mitochondrial transhydrogenase has been reported previously to be inhibited by high, rather non-physiological concentrations (in the range of 2-20 mM) of divalent cations. We show that the enzyme could be activated by low (from about 1 microM to 1 mM) concentrations of Ca2+ and Mg2+, which are within physiological range. These results bring in line the effects observed with mitochondrial enzyme to the findings with bacterial transhydrogenases. The activation of transhydrogenase by divalent cations is interpreted as an increase in affinity of the NADP(H)-binding site of the enzyme-NAD(H) complex. Reported effects of the metal ions could be important for the enzyme function in vivo. PMID- 8369342 TI - Cloning and sequence of the Rhizobium leguminosarum biovar phaseoli fixA gene. AB - We report the identification and cloning of Rhizobium leguminosarum biovar phaseoli fixABCX homologous genes and the complete nucleotide sequence of the fixA gene. The corresponding gene product is highly homologous to the Rhizobium meliloti and Azorhizobium caulinodans FixA proteins. Putative NtrA- and NifA binding sites are identified in the fixA promoter region. PMID- 8369343 TI - Dependence of normalized protein catabolic rate on Kt/V in continuous ambulatory peritoneal dialysis: not a mathematical artifact. PMID- 8369344 TI - The role of vaccination in the prevention of staphylococcal peritonitis in continuous ambulatory peritoneal dialysis. PMID- 8369345 TI - Cross sectional assessment of weekly urea and creatinine clearances and indices of nutrition in continuous ambulatory peritoneal dialysis patients. AB - OBJECTIVE: To perform a cross sectional analysis in 71 patients on continuous ambulatory peritoneal dialysis (CAPD) to identify significant correlations of weekly small solute clearances and indices of nutritional status with each other and with patient demographics and other commonly monitored clinical and laboratory parameters. DESIGN: This was a retrospective, cross sectional analysis in 71 patients on CAPD from less than 1 to 105 patient-months (average, 20 months). SETTING: An outpatient CAPD program. PATIENTS: All patients on CAPD in our program at the time of the study willing to undergo the clearance and nutritional status measurements. INTERVENTIONS: No interventions other than the monitoring of their status. MAIN OUTCOME MEASURES: Weekly small solute clearances, dietary protein intake, serum albumin, lean body mass, net protein catabolic rate, and urinary and dialysate nitrogen. RESULTS: Weekly Kt/V urea (weekly urea clearance normalized to total body water) of at least 1.7 and weekly total creatinine clearances (liter/week/1.7 m2) of at least 50 are associated with net protein catabolic rates (PCR) greater than 0.9 g/kg of normalized body weight in average CAPD patients. Kt/V urea and net PCR correlate significantly with serum albumin. High transporters identified by the peritoneal equilibration test have greater albumin losses and lower serum albumin concentrations. Estimates of lean body mass correlate significantly with serum albumin and net PCR; lean body mass correlates significantly and inversely with age. CONCLUSIONS: Greater small solute clearances are associated with better nutritional status. PMID- 8369346 TI - Assessment of dialysis dose by measured clearance versus extrapolated data. AB - OBJECTIVE: To determine whether estimates of daily dialysis clearance of creatinine and urea, based on data from the 4-hour peritoneal equilibration test, correlate well with daily dialysis clearance measured by 24-hour dialysate collection in chronic ambulatory peritoneal dialysis patients. DESIGN: Prospective study in which each subject collected all dialysate from a 24-hour period and then immediately thereafter underwent a standard peritoneal equilibration test (PET). Daily clearances of creatinine and urea were calculated from 24-hour dialysate collections by standard methods and then were compared with several estimates of 24-hour clearance based on PET data. SETTING: Single peritoneal dialysis unit of a university teaching hospital. PATIENTS: Thirty-six stable patients on continuous ambulatory peritoneal dialysis (CAPD). MAIN OUTCOME: The estimated values for daily dialysis clearance both overestimated and underestimated the measured 24-hour clearance. The correlation coefficient between the extrapolations and the actual 24-hour clearances ranged from 0.63 0.68. The range of discordance for daily creatinine clearance was from -2530 mL/day to +2199 mL/day. For daily urea clearance, the range of discordance was from -2103 mL/day to +1940 mL/day. The peritoneal membrane transport characteristics of the individual patient did not predict whether the extrapolation overestimated or underestimated the measured daily clearance. CONCLUSION: Extrapolation of PET data is not a reliable method to estimate the dose of dialysis delivered to the patient. A 24-hour collection of dialysis is necessary for this determination. PMID- 8369347 TI - Determining peritoneal dialysis prescriptions by employing a patient-specific protocol. AB - OBJECTIVE: To develop a formula that would permit a rapid and simple calculation of required dialysate volume needed to provide a predetermined daily creatinine clearance. DESIGN: Prospective study of peritoneal dialysis patients followed for 6 months. SETTING: A primary care teaching hospital in New York. PATIENTS: Twenty six patients beginning peritoneal dialysis entered and completed the study. INTERVENTION: By employing each patient's measured peritoneal equilibration test (PET) and a standard clearance formula, a patient-specific treatment protocol (PSP) was calculated. The PET 2-hour D/Pcreat was used for continuous cycling peritoneal dialysis (CCPD) and the 4-hour D/Pcreat was used for patients on continuous ambulatory peritoneal dialysis (CAPD) to determine a PSP that would provide a minimum of 6 L of creatinine clearance daily. MAIN OUTCOME MEASURES: Patients were followed for 6 months to assess the ability of this approach of maintaining acceptable levels of blood urea nitrogen, creatinine, albumin, and hematocrit over the 6-month period of observation. RESULTS: Our study of 26 patients revealed that only 6 patients (23%) could be treated with the standard prescription of 8 L/day on CAPD. The remaining 77% of our patients required 9-13 L/day for CAPD and 12-21 L/day for CCPD. All patients were free of uremic symptoms and demonstrated acceptable biochemical parameters over a 3-6 month period of observation. CONCLUSIONS: A patient-specific protocol utilizing individually derived PET data provides an acceptable and easy to calculate initial treatment prescription for each patient that avoids the necessity for trial and error that has heretofore been employed. PMID- 8369348 TI - A comparison of peritoneal dialysis-related infections in short- and long-term peritoneal dialysis patients. AB - OBJECTIVE: We hypothesized that the infection rates and organisms would differ in long-term peritoneal dialysis (PD) patients versus those who died or transferred to hemodialysis during the first 4 years on PD. DESIGN: Data on PD-related infections and outcome were collected from 1979 to 1991 (prospectively since 1982). SETTING: The patients were followed at University and Veterans Administration dialysis centers. PATIENTS: All patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD) for 4 years or more (n = 43) were compared to those patients who died or transferred to hemodialysis prior to 4 years on PD (n = 213). MAIN OUTCOME MEASURES: Infection rates due to various microorganisms and reasons for transfer to hemodialysis were examined. RESULTS: Peritonitis rates were 1.2/year versus 0.8/year (p < 0.001) in patients on peritoneal dialysis less than 4 years compared to those on 4 years or more, respectively, a difference due to S. epidermidis (0.32/year vs 0.20/year, p = 0.0001) and gram-negative rods other than P. aeruginosa (0.15/year versus 0.06/year, p < 0.001). Exit-site infection rates were 1.2/year versus 0.7/y (p < 0.0001) in the patients on less than 4 years compared to those on 4 years or more, respectively, a difference in part due to S. aureus (0.45/year vs 0.3/year, p < 0.001) and other gram-positive organisms (0.28/year vs 0.10/year, p < 0.001). The rates of infections that were similar in the two groups were tunnel infections (0.2/year), P. aeruginosa infections, and S. aureus peritonitis (0.18/year vs 0.14/year, p = 0.09). S. aureus was the most common cause of exist site and tunnel infections in both groups. Forty-two percent of the patients on PD 4 years or more subsequently transferred to hemodialysis, most often due to infections, especially S. aureus. CONCLUSIONS: Although infection rates are lower in patients on peritoneal dialysis 4 years or more, S. aureus and P. aeruginosa continue to account for a high proportion of the infections. Improvement in technique survival will require prevention of these infections. PMID- 8369349 TI - Chronic tunnel infections in children: removal and replacement of the continuous ambulatory peritoneal dialysis catheter in a single operation. AB - OBJECTIVE: Chronic tunnel infections often necessitate the removal of the continuous ambulatory peritoneal dialysis (CAPD) catheter. Most published studies advocate postponing the insertion of a new catheter for several weeks. For young children it will be particularly difficult to wait this length of time, since vascular access may be cumbersome, and hemodialysis may not be well tolerated. The present study describes the results of the simultaneous removal and replacement of the CAPD catheter. DESIGN: Twenty-three Toronto Western Hospital II catheters were inserted in 17 children because of infectious complications (21 chronic tunnel infections; 2 recurrent peritonitis) in a single operation under appropriate antibiotic prophylaxis. The new catheter was inserted at the contralateral side of the abdomen with the deep cuff in the midline, using the same entrance to the peritoneal cavity. Dialysis was resumed immediately after the operation. SETTING: A university pediatric dialysis unit. PATIENTS: Seventeen children (mean age 3.7 years; range 1.0-8.5 years) were studied. In this group 23 catheters were replaced. RESULTS: In four cases a relapse of the tunnel infection was observed within 3 months. All other cases remained free of infection for a period of at least 6 months. The main causative microorganism was Staphylococcus aureus (15 occurrences). CONCLUSION: It is not necessary to interrupt peritoneal dialysis for the replacement of a CAPD catheter because of infectious complications. PMID- 8369350 TI - In vitro study of the mechanism of potassium transport into human mesothelial cells. I: Effect of hyperosmolality. AB - OBJECTIVE: To study the mechanism(s) of potassium transport into human mesothelial cells (HMC) exposed to osmotic solutes. DESIGN: Using potassium analog 86Rb, we evaluated its intracellular transport through three pathways: 1. blocked by ouabain; 2. blocked by furosemide but not by ouabain; 3. blocked by neither furosemide nor ouabain. Experiments were performed in a normotonic medium (control) or in a medium supplemented with osmotic solutes (glucose, glycerol, mannitol). Both the acute and chronic effects of osmotic solutes on potassium transport were studied. RESULTS: The acute exposure of mesothelial cells to osmotic solutes modifies the intracellular transport of potassium through all studied channels, and the effect is specific for every solute. In mesothelial cells exposed over 7 days to glucose (90 mM), the intracellular transport via ouabain- and furosemide-blocked channels is decreased, whereas it is increased through the third pathway. Total intracellular accumulation of 86Rb (potassium) ions in mesothelial cells cultured in a medium supplemented with various concentrations of glucose is decreased, and this effect is proportional to the concentration of glucose in the medium. CONCLUSIONS: The intracellular transport of potassium in mesothelial cells is regulated through at least three independent mechanisms. Acute or chronic exposure of mesothelial cells to a hypertonic medium affects the intracellular accumulation of potassium, and this effect is specific for the various osmotic solutes. PMID- 8369351 TI - Heat sterilization of fluids for peritoneal dialysis gives rise to aldehydes. AB - OBJECTIVE: To chemically identify and quantify glucose degradation products in heat sterilized fluids for peritoneal dialysis. DESIGN: Three different brands of commercial PD-fluids and one laboratory made fluid, sterilized either by heat or filtration, were investigated for the presence of aldehydes. MEASUREMENTS: Aldehydes were identified and quantified using high performance liquid chromatography and gas chromatography. RESULTS: The tested brands of heat sterilized PD-fluids were found to contain several different aldehydes while the sterile filtered PD-fluid contained none. The highest concentrations in commercial PD-fluids of these aldehydes were: acetaldehyde (420 microns), glyoxal (14 microns), methylglyoxal (12 microns) and formaldehyde (11 microns). Valeraldehyde was also identified but not quantified. The presence of 5-HMF (15 microns) and 2-furaldehyde (2 microns), which has been identified by others, was confirmed. CONCLUSIONS: The heat sterilization of commercial PD-fluids gives rise to several aldehydes which may contribute to adverse effects of PD-fluids on patients. PMID- 8369352 TI - The serum complement system in children on continuous ambulatory peritoneal dialysis. AB - OBJECTIVE: During continuous ambulatory peritoneal dialysis (CAPD), the loss of complement factors via the dialysate may cause complement deficiencies. This hypothesis was tested in a group of children treated with CAPD. DESIGN: Classical (CH50) and alternative (AP50) complement activity and serum levels of factors C1q, C3, C4, C3d, B, D, and P in CAPD patients were compared to normal controls and to children with preterminal renal failure. SETTING: Patients were seen in a university hospital; normal controls were seen in an outpatient clinic of a general hospital. PATIENTS: A group of 22 children on CAPD was compared to a normal control group of 44 children and to a group of 12 children with preterminal renal failure with a creatinine clearance below 25 mL/min/1.73 m2. RESULTS: CH50, AP50, C3, and B were not significantly different from the control group in both the CAPD and preterminal groups. Factors C1q (p = 0.01) and C4, C3d, D, and P (p < 0.001) were higher in the CAPD group in comparison to the normal control group. The factors D (p < 0.001) and P (p = 0.02) were also elevated in the preterminal group. For the measured factors there was no significant difference between the CAPD group and the preterminal group. CONCLUSIONS: There is no deficiency of complement in children treated with CAPD. High levels of C3d and D can be explained by the reduction of their elimination by the kidney. The increased levels of the other factors are presumably due to increased synthesis in renal failure. This does not seem to be caused by CAPD. PMID- 8369353 TI - Calcium and magnesium mass transfer in peritoneal dialysis patients using 1.25 mmol/L calcium, 0.25 mmol/L magnesium dialysis fluid. AB - OBJECTIVE: To examine the effect of a reduced calcium/magnesium dialysis fluid (1.25/0.25 mmol/L, respectively) on calcium and magnesium mass transfer in both 1.36% and 3.86% glucose solutions. DESIGN: Each patient underwent four test exchanges, two with a standard dialysis fluid containing 1.36% and 3.86% glucose, and two with a reduced calcium/magnesium fluid containing 1.36% and 3.86% glucose. Calcium and magnesium were measured in dialysate and serum at 0 and 240 minutes. SETTING: Single renal unit of a university teaching hospital. PATIENTS: Sixteen patients established on CAPD, and peritonitis-free, for at least 3 months. RESULTS: A lower dialysate calcium results in negative mass transfer when serum-ionized calcium exceeds dialysate calcium (mean -0.21 +/- 0.15 mmol/exchange), and positive mass transfer when serum-ionized calcium is less than dialysate calcium in 1.36% glucose solutions (mean 0.57 +/- 0.18 mmol/exchange). A negative correlation was found between serum-ionized calcium level and calcium mass transfer. With a 3.86% reduced calcium/magnesium solution, calcium mass transfer is always negative (-0.88 +/- 0.18 mmol/exchange) due to ultrafiltration and solute drag. Fifteen patients were found to be hypermagnesemic at the time of the study. Magnesium mass transfer was neutral with the standard 1.36% glucose fluid (mean -0.01 mmol/exchange), but negative with the reduced calcium/magnesium 1.36% glucose fluid (mean -0.58 +/- 0.13 mmol/exchange). With the 3.86% glucose solution, both fluids produced negative magnesium mass transfer (mean -0.32 +/- 0.11 and -1.07 +/- 0.11 mmol/exchange for standard and reduced calcium/magnesium fluids, respectively). CONCLUSIONS: We conclude that this fluid formulation should reduce hypercalcemia and hypermagnesemia in CAPD patients. PMID- 8369354 TI - Survival of 138 surgically placed straight double-cuff Tenckhoff catheters in patients on continuous ambulatory peritoneal dialysis. AB - OBJECTIVE: To determine the natural history of a surgically placed Tenckhoff catheter in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective 7-year study analyzing catheter survival of all catheters using the Kaplan-Meier life table methodology. SETTING: Teaching hospital, department of nephrology. PATIENTS: One hundred and fifteen unselected patients beginning CAPD. INTERVENTIONS: Removal of the catheter required for the following complications: exit-site or tunnel infections or relapsing peritonitis, outflow obstruction, pericatheter leak, and development of hernias. MAIN OUTCOME MEASURES: Period between insertion and removal of the catheter. RESULTS: The cumulative survival of all catheters after 1, 2, and 3 years of CAPD was 87%, 69% and 65%. Catheter survival of the first versus the second catheter after 1 year was significantly longer (p = 0.03). The difference was not significant in relation to diabetes, age, and sex. Infectious complications caused 61% (n = 19) of all 31 catheter failures, mainly due to tunnel infections caused by Staphylococcus aureus (n = 12). "Mechanical" complications accounted for 49% (n = 12) of catheter failures. Eight of 12 mechanical complications were outflow failures. Seven patients had to be transferred to hemodialysis. CONCLUSIONS: The straight Tenckhoff catheter is a reliable peritoneal access device for CAPD in an unselected patient population. PMID- 8369355 TI - Destructive spondyloarthropathy in a patient on continuous ambulatory peritoneal dialysis for 13 years. AB - Since 1984 there have been reports of a destructive spondyloarthropathy occurring in patients on long-term hemodialysis. The primary abnormality appears to be an accumulation of beta 2-microglobulin, which is not adequately removed by dialysis, and forms amyloid deposits in articular and periarticular tissues. We report a case of this disease in a patient treated only by peritoneal dialysis. While this form of treatment may delay the development of arthropathy, as compared to hemodialysis, it does not prevent it. An increasing incidence of this disorder may be expected, since increasing numbers of patients have been on long term peritoneal dialysis. PMID- 8369356 TI - Influence of mothers on school adjustment of continuous ambulatory peritoneal dialysis children. AB - In school children on continuous ambulatory peritoneal dialysis (CAPD), school adjustment is regarded as an important indicator for comprehensive medical care. The aim of the present study was to examine the influence of mothers on school adjustment of CAPD children. The children tended to indicate school maladjustment with school absenteeism and poor relationships with friends. The mothers were characterized by poor independence, poor achievement orientation, strong emotional reliance, and lack of social self-confidence, indicating emotional instability. The family environment, including the mother's psychological condition, was strongly associated with the children's maladjustment to school. The results suggested the necessity of comprehensive medical care for these children and their mothers. PMID- 8369357 TI - Assessing the adequacy of peritoneal dialysis. PMID- 8369358 TI - Serial changes of serum beta-2-microglobulin in CAPD. PMID- 8369359 TI - Group B Streptococcus (agalactiae) peritonitis and bacteremia associated with CAPD. PMID- 8369360 TI - Death associated with Pseudomonas peritonitis in malnourished elderly diabetics on CAPD. PMID- 8369361 TI - Literature. July-September 1993. PMID- 8369362 TI - Potential clinical use of the EDTA-infusion test. AB - The introduction of assays for the intact parathyrin (parathyroid hormone) has dramatically improved the diagnosis and follow-up of patients with primary hyperparathyroidism. However, in some patients with mild or intermittent hypercalcaemia, when plasma concentrations of intact parathyrin may be within the normal reference concentrations, the diagnosis of primary hyperparathyroidism may still be problematic. In these patients, the EDTA-infusion test is of potential value, as it also might be in patients with equivocal operative findings. PMID- 8369363 TI - Evaluation of the creatinine assay on the Reflotron analyser under centralized and non-centralized conditions. AB - The creatinine assay, performed on Reflotron "dry chemistry" analysers in six offices of general practitioners, was evaluated as part of a project on the quality of laboratory determinations in decentralized situations. The method itself was evaluated before this investigation was started. Differences were noticed between Reflotron machines, batches of strips, and various types of sample, viz. heparin-treated blood or plasma gave higher results than serum of EDTA-treated samples. All Reflotron results were lower in comparison with wet chemistry methods. The "dry chemistry" technique was not influenced by the presence of glucose or bilirubin (below 170 mumol/l); haemoglobin interfered. By simultaneous sampling, all creatinine determinations performed on whole EDTA blood in the general practitioners offices were repeated on serum in centralized laboratories using "wet chemistry" techniques. In this comparison 3% of all creatinine determinations in general practitioners offices were outside the 95% confidence interval. We conclude that the creatinine determination on the Reflotron may be used in general practitioners office testing as long as the general practitioner is aware of its limitations and can rely on a "reference" laboratory for training, quality control and repetition of unexpected results. PMID- 8369364 TI - Calibrators and control samples for bilirubinometers. AB - The different matrix properties of neonatal serum and commercial control samples can lead to considerable errors in the calibration and control of bilirubinometers. These difficulties can be avoided by calibration with serum from healthy adults which is supplemented with unconjugated bilirubin. But this procedure is impracticable for most routine laboratories. Under certain preconditions, control samples, with bilirubin concentrations determined with correctly calibrated bilirubinometers or spectrophotometers, are also suitable as calibrators. This was established by determination of the bilirubin concentration of 16 different control samples, using both the reference method and correctly calibrated bilirubinometers or spectrophotometers in three or four specialist laboratories. This was also confirmed in several interlaboratory surveys, some involving up to 72 laboratories. The results of these investigations show that a control sample should be used for the calibration of a bilirubinometer only if it meets the following preconditions: 1. There should be no significant difference between the bilirubin values determined with the reference method and with a correctly calibrated spectrophotometer or bilirubinometer. 2. The bilirubin concentration should lie in the range 230-300 mumol/l. The photometric response of bilirubinometers has a limited linear range, so that analytical results greater than 300 mumol/l must be rated as basically unreliable. PMID- 8369365 TI - Determination of nerve growth factor concentrations in human samples by two-site immunoenzymometric assay and bioassay. AB - Nerve growth factor is a neurotrophic protein which is known to act on sympathetic and sensory neurons and on the magnocellular cholinergic neurons of the basal forebrain. We quantified nerve growth factor in human tissue and body fluids by two methods, a rapid and sensitive two-site immunoenzymometric assay and a bioassay using dissociated chick dorsal root ganglion neurons. The two-site immunoenzymometric assay detects nerve growth factor in concentrations as low as 0.5-2.5 ng/l. Using a monoclonal antibody to mouse nerve growth factor, we found that the signal of the antibody for recombinant human nerve growth factor is about 60-90% of the signal for mouse nerve growth factor. As a control for the specificity of our data, a bioassay for nerve growth factor was performed and the results showed a good correlation. The highest nerve growth factor concentrations were found in sciatic nerve (2.5 ng/g wet weight), cardiac atrium muscle (1.5 ng/g wet weight) and in the central nervous system in the hippocampus (1.9 ng/g wet weight). Lower nerve growth factor concentrations were measured in human sera (0.2 ng/g wet weight). No nerve growth factor was detectable in cerebrospinal fluid. The distribution of human nerve growth factor-rich tissues is similar to that reported for rat tissues. PMID- 8369366 TI - Monitoring cyclosporin A (ciclosporin, INN) concentrations in whole blood: evaluation of the EMIT assay in comparison with HPLC and RIA. AB - We report here on an evaluation of the enzyme-multiplied immunoassay technique (EMIT) from Syva for cyclosporin A (ciclosporin, INN) concentration measurements in whole blood. The assay incorporates a monoclonal antibody for specific determination of ciclosporin. Measurements by EMIT were performed on the Cobas Mira-S from Roche. A total of 197 blood specimens from heart-(n = 74), kidney-(n = 62) and liver-(n = 61) transplant recipients were analyzed. EMIT values correlated well with those obtained by HPLC, as well as with those obtained by a selective radioimmunoassay (INCStar). Ciclosporin concentrations determined by EMIT (y) agreed very well with those by RIA, and averaged 8% higher than those by HPLC (x) [n = 197, mean = 143 micrograms/l, y = 155 micrograms/l, y = 1.09x - 0.6, r = 0.969]. Within-series and between-days CVs ranged from 4.6% to 7.3% for ciclosporin concentrations > 100 micrograms/l, and from 5.5% to 10.5% for ciclosporin concentrations between 69.5 micrograms/l and 100 micrograms/l. The within-series CV for a concentration of 45.5 micrograms/l was 14.8%. Calibration employing a 2-point mode instead of a continuous mode of UV-signal evaluation improved the precision of the EMIT assay at low ciclosporin concentrations. Sample pretreatment required thorough and skillful performance to avoid false positive ciclosporin measurements. We conclude that the EMIT assay is specific, and rapid to perform. It can be effectively used in the monitoring of ciclosporin concentrations in whole blood. PMID- 8369367 TI - Development and evaluation of a time-resolved immunofluorimetric assay for thyrotropin. AB - The assay described in this article is based on microtitre plate technology; it employs an europium label. The streptavidin-biotin system has been used and all components are commercially available. The lower detection limit of the assay is below 0.003 mU/l; the standards are made up in newborn calf serum. Correlation with a commercially available immunoluminometric assay (Berilux--Behringwerke) was excellent (r = 0.92, n = 201 data pairs, range covered 0-10 mU/l). The regression line using a double logarithmic transformation was: (log y) = 0.91 (log x)-0.08. The assay precision at the clinical limits of decision--i.e. between hyper- and euthyroidism (0.2 mU/l) and eu- and hypothyroidism (4 mU/l)- was acceptable. The median coefficient of variation was 1.93% in the range 0.02-1 mU/l and 2.11% in the range 1.0-3.5 mU/l, with both values being determined from precision profiles using 214 and 188 data pairs respectively. Inter-assay coefficients of variation determined in over 30 consecutive assays were under 6% in the range 1.3-20 mU/l. From 201 sera measured in both assays, 194 sera gave clinically identical values; 8 sera gave clinically discrepant values. The assay has a large dynamic range covering a concentration range of above 5 decades, with the count ratio between the 100 mU/l standard and the zero standard being in excess of 4150:1. A high dose hook effect was first seen in excess of 500 mU/l. The maximum signal was achieved around 150 mU/l, which registered around 8 x 10(6) counts per second, a figure more than 8000 times higher than that in the zero standard. PMID- 8369368 TI - Establishment of reference ranges for follitropin and lutropin in neonates, infants, children and adolescents. AB - Follitropin was determined in the sera of 645 probands, and lutropin in the sera of 649 probands between the ages of 5 days and 18 years (neonates, infants, children and adolescents), using microparticle-enzyme-immunoassays (MEIA) on the IMx from Abbott Laboratories. The proband collective was divided into 9 age groups and each group into males and females. In accordance with the recommendations of the International Federation of Clinical Chemistry, the 95% scatter range was taken as the reference range. In some age groups, the ranges for individual hormones showed a significant sex difference. Age groups without significant sex differences were combined and evaluated statistically as a single group. Only a few reference groups showed a normal Gaussian distribution. In addition to the 50th percentile, the 2.5th and 97.5th, or the zero and 95th percentiles were determined for all reference groups. Minimal and maximal values were also determined. The U-test of Mann & Whitney was used to test for significant differences between the individual reference groups. Groups showing no significant differences were combined, and reference ranges were finally calculated for follitropin and lutropin in the serum of healthy neonates, infants, children and adolescents. PMID- 8369369 TI - Measuring Bence Jones proteins with antibodies against bound immunoglobulin light chains: how reliable are the results? AB - Protein mass concentrations of nine individual urinary Bence Jones proteins were determined via protein dry weight and compared (i) to immuno-nephelometric measurements using two different antisera against bound light-chains and (ii) to total protein concentrations determined by trichloroacetic acid nephelometry and the Biuret method. In each case, these four measurements differed significantly from each other and from the expected value (as determined by protein dry weight). The extent and direction of deviation were different for each measurement and varied between cases, but similar patterns were observed in different samples from the same patient. Apparently, these measurements can not be quantitatively compared between different individual Bence Jones proteins, but can be interpreted in terms of disease activity and therapeutic success for each patient. Accordingly, the quantitative expression of Bence Jones proteins should be restricted to relative terms, e.g. "arbitrary units" or "serum light-chain equivalents". This avoids the (potentially incorrect) statement of protein mass concentrations. PMID- 8369370 TI - Optimum experimental designs for properties of a compartmental model. AB - Three properties of interest in bioavailability studies using compartmental models are the area under the concentration curve, the maximum concentration, and the time to maximum concentration. Methods are described for finding designs that minimize the variance of the estimates of these quantities in such a model. These methods use prior information. Both prior estimates and prior distributions are used. The designs for an open one-compartment model are compared with the corresponding D theta-optimum design for all parameters and also with designs that minimize the sum of the scaled variances of the individual properties. PMID- 8369371 TI - t-REML for robust heteroscedastic regression analysis of mitochondrial power. AB - The paper reports a long series of observations on two statistically independent variates which have different nonlinear regressions on the same parameter vector. In our analysis of the data, heteroscedasticity is handled by residual maximum likelihood, REML, but to cope with outliers as well, REML based on a t specification, called t-REML, is introduced. The data are the results of factorial experiments designed to model the quantitative performance of mitochondria generating aerobic power. The response variates are flux, measured as respiration, and ATP potential as log(ATP/ADP). The background of metabolism and oxidative phosphorylation is briefly sketched. PMID- 8369372 TI - An index of tumorigenic potency. AB - A new index of tumorigenic potency is derived using a survival-adjusted quantal response estimator given by Bailer and Portier (1988, Biometrics 44, 417-431). The small-sample bias and mean squared error properties of this estimator are explored using computer simulations of animal carcinogenicity experiments and are compared to the characteristics of the TD50, an estimator proposed by Sawyer et al. (1984, Biometrics 40, 27-40). It is observed that this new index tends to have smaller bias and mean squared error relative to the TD50 over varying shapes of the tumor onset distribution, levels of tumor lethality, and levels of treatment lethality. PMID- 8369373 TI - A Weibull model for the estimation of tumorigenic potency. AB - In this paper, a new method of estimating tumorigenic potency is proposed that takes into account information on survival and, when available, the underlying cause of death. Specifically, Weibull distributions are used to describe the time to tumor occurrence (X), the time to death as a result of tumor occurrence (Y), and the time of death from causes other than tumor occurrence (Z). The distributions of X and Y are related via a lethality parameter p lying between 0 (incidental tumors) and 1 (rapidly fatal tumors). The index of tumorigenic potency is defined as the dose inducing a specified excess tumor response rate (in the range of 25%-50%) following exposure for an extended period encompassing most of the expected lifespan. Application of the proposed method is illustrated using several data sets taken from the literature. PMID- 8369374 TI - Regression analysis of grouped survival data: informative censoring and double sampling. AB - To analyze grouped survival data subject to informative censoring, we propose the following two-part model: a logistic regression model for the hazard for failure, given covariates and a logistic regression model for the hazard for informative censoring, given time of failure and covariates. We fit the model to survival data arising from a double sampling design: In a full follow-up (FF) sample subjects are followed after censoring, and in a partial follow-up (PF) sample subjects are not followed after censoring. We illustrate the methodology using data from a study of wound infection in which patients in the PF sample are censored by release from the hospital, whereas patients in the FF sample are followed after hospital release. We discuss identifiability when there is only a PF sample. We also consider how the allocation between the PF and FF samples affects the precision of estimates. PMID- 8369375 TI - Selection designs for pilot studies based on survival. AB - In cancer clinical trials new regimens are typically tested for antitumor activities in patients with advanced disease. The promising ones are then compared to the standard treatment in a randomized study, sometimes performed on patients with earlier-stage disease. When there are multiple promising regimens, it may not be possible to compare all of them to the control group because of the prohibitive sample size and study length requirements. We propose a design that uses the Cox regression model to select a best treatment based on survival before the randomized comparison. Sample sizes for an asymptotically correct selection probability of .90 are presented for Weibull survival distributions with parameters in a range we consider to be of practical interest. Simulations verify that the asymptotic approximations to the correct selection probabilities are quite satisfactory. Simulations also indicate that the procedure is reasonably robust to the proportional hazards assumption. In contrast to the two-stage screening design recommended by Schaid, Wieand, and Therneau (1990, Biometrika 77, 507-513), our design has the advantage of fitting naturally to a progression of cancer trials where the selection and comparison phases are carried out on different populations of patients. When the population of interest stays the same, our design can be more conservative on the average but offers the opportunity to base the comparative trial on the experience gained during the selection phase. PMID- 8369376 TI - Evaluating constraints that allow survival-adjusted incidence analyses in single sacrifice studies. AB - Ideally, analyses of tumor incidence data from long-term animal experiments should allow the incidence rates to vary with age, without restricting tumor lethality, without requiring data on cause of death, and without assuming independence of competing risks. This article focuses on nonparametric methods that not only satisfy these conditions, but also accommodate studies having just one sacrifice time, by constraining the effects of age on one of the three functions used to characterize the likelihood. Several constrained analyses were evaluated using data on over 18,000 mice from the ED01 study. Of the five constraints considered, only the assumption of constant differences between the death rates for animals with and without the tumor of interest produced reasonable results across a wide range of tumor lethalities. PMID- 8369377 TI - Estimation of two ordered mean residual lifetime functions. AB - In many statistical studies involving failure data, biometric mortality data, and actuarial data, mean residual lifetime (MRL) function is of prime importance. In this paper we introduce the problem of nonparametric estimation of a MRL function on an interval when this function is bounded from below by another such function (known or unknown) on that interval, and derive the corresponding two functional estimators. The first is to be used when there is a known bound, and the second when the bound is another MRL function to be estimated independently. Both estimators are obtained by truncating the empirical estimator discussed by Yang (1978, Annals of Statistics 6, 112-117). In the first case, it is truncated at a known bound; in the second, at a point somewhere between the two empirical estimates. Consistency of both estimators is proved, and a pointwise large-sample distribution theory of the first estimator is derived. PMID- 8369378 TI - Epidemiologic assessment of risks of adverse reactions associated with intermittent exposure. AB - Measures of risk of adverse reactions, such as the absolute risk, the relative risk, and the excess risk, are analyzed for individuals who are exposed occasionally for periods of varying duration. This type of exposure is of particular importance for the epidemiologic assessment of drug safety. A Poisson point process model that allows for the simultaneous consideration of concomitant factors is derived for the estimation of the hazard rates. The model can judge acute adverse reactions and is applicable not only for rare risks since an undesired effect may occur repeatedly for an individual. Hazard estimation is achieved with the aid of the maximum likelihood method for several sampling designs, such as cohort studies, case-cohort studies, and case studies. In the latter design only those individuals who have had an adverse reaction during the time of observation are considered for hazard estimation. An application to the analysis of wound-healing impairments is given. PMID- 8369379 TI - Conditional regression analysis of the exposure-disease odds ratio using known probability-of-exposure values. AB - Conditional inference methods are proposed for the odds ratio between binary exposure and disease variables when only the probability of exposure is known for each study subject. We develop a conditional likelihood approach that removes nuisance parameters and permits inferences to be made about important parameters in log odds ratio regression models. We also discuss a heuristic procedure based on estimating the (unknown) number of truly exposed individuals; this procedure provides a simple framework for interpreting our likelihood-based statistics, and leads to a Mantel-Haenszel-type estimator and a goodness-of-fit test. As an example of the use of this methodology, we present an analysis of some genetic data of Swift et al. (1976, Cancer Research 36, 209-215). PMID- 8369380 TI - Random-effects models, for longitudinal data using Gibbs sampling. AB - Analysis of longitudinal studies is often complicated through differences amongst individuals in the number and spacing of observations. Laird and Ware (1982, Biometrics 38, 963-974) proposed a linear random-effects model to deal with this problem. We propose a generalisation of this model to accommodate multiple random effects, and show how Gibbs sampling can be used to estimate it. We illustrate the methodology with an analysis of long-term response to hepatitis B vaccination, and demonstrate that the methodology can be easily and effectively extended to deal with censoring in the dependent variable. PMID- 8369381 TI - Nonparametric procedures for comparing umbrella pattern treatment effects with a control in a one-way layout. AB - In this paper we are concerned with comparing umbrella pattern treatment effects with a control in a one-way layout. The problem of testing whether there is at least one treatment that is better than the control is considered. Distribution free tests are proposed for both cases where the peak of the umbrella is known or unknown. Approximate small-sample critical values are presented and the results of a Monte Carlo power study are discussed. PMID- 8369382 TI - Qualitative interactions in multifactor studies. AB - In clinical trials qualitative interaction or crossover interaction is said to occur when one treatment is superior for some sets of patients and the alternative treatment is superior for other subsets. Here we propose a definition of no qualitative interaction with respect to a single continuous covariate which implies that one treatment is superior to the other treatment over a prespecified range of the covariate. Further, in studies involving patients cross-classified by two or more prognostic factors, we define a marginal qualitative interaction with respect to a treatment factor and a prognostic factor by averaging in some sense over the remaining prognostic factors. In some situations, the methodology of Gail and Simon (1985, Biometrics 41, 361-372) is shown to be appropriate. Their procedure assumes independent estimates of treatment effect for each subset of patients and this may not be appropriate for the generalizations we propose. Therefore, we generalize the procedure of Gail and Simon to the case of two correlated estimates of treatment effect, providing a table of critical values. Results for one-sided tests for the case of J correlated estimates are also obtained. We also present an example illustrating our procedure. PMID- 8369383 TI - The contribution of individual variables to Hotelling's T2, Wilks' lambda, and R2. AB - We examine the effect of each variable on the following statistics: the one sample and two-sample Hotelling's T2, Wilks' lambda for multivariate analysis of variance, and R2 in multiple regression. For T2, the net effect of each variable is an increase in the multivariate statistic, and the particular factors determining the amount of increase are (i) the multiple correlation of the variable with all other variables, and (ii) how well the variable's contribution to falsifying the hypothesis can be linearly predicted from the other variables. The effect of each predictor variable on R2 is similar to the effect of each variable on T2. For Wilks' lambda, each variable induces a decrease, due to (i) the F for that variable alone, and (ii) the change in multiple correlation from within-sample to total-sample. PMID- 8369384 TI - Modeling the Ames Salmonella/microsome assay. AB - Of the many short-term tests for mutagenicity that have been proposed in recent years, the Ames Salmonella/microsome assay is the single most widely used and most thoroughly validated in vitro test system. This assay uses cells cultured in a soft agar containing a trace amount of histidine to allow growth of auxotrophic bacteria, and is designed to detect reverse mutations from auxotrophic cells to histidine-independent prototrophic cells. In this paper, statistical models that have been proposed for the analysis of Ames test data are reviewed, including those of a mechanistic and empirical nature. An extension to the class of biologically based models derived by Margolin, Kaplan, and Zeiger (1981, Proceedings of the National Academy of Sciences 78, 3779-3783) is proposed by allowing for diffusion of histidine within the plate agar. Quasi-likelihood methods for estimating the model parameters are presented, and applied to 1,120 data sets from a recent collaborative trial sponsored by the International Programme on Chemical Safety. PMID- 8369385 TI - Fixed-distance latent class models for the analysis of sets of two-way contingency tables. AB - This paper develops and describes the application of modified latent class models for analyzing sets of two-way contingency tables. The proposed fixed-distance models differ from traditional latent class models in that the assumption of local stochastic independence is superseded by allowing interactions of the manifest variables within each class, which can be represented by a single association parameter. As an example, two data sets on eye color by hair color [collected in Caithness (N1 = 5,387) and Aberdeen (N2 = 22,361)] and fixed distance models with up to six classes (three classes per data set) are considered, finally leading to satisfactory fit and rather simple interpretation. PMID- 8369386 TI - Interval estimation under two study designs for kappa with binary classifications. AB - Cornfield's test-based method of setting a confidence interval on a parameter associated with a two-by-two contingency table is adapted for use with the measure of agreement kappa. One-sided confidence intervals derived in this way are compared to other intervals proposed for kappa under two study designs. Both designs involve two ratings per subject on a dichotomous scale. In one design the same two raters make all evaluations; in the other, possibly different pairs of raters evaluate different subjects, or the same rater carries out a pair of independent assessments for each subject. It is shown through simulation that lower bounds based on Cornfield's test-based method attain the nominal coverage probability more often than other intervals proposed in the literature. PMID- 8369387 TI - Higher-order kappa-type statistics for a dichotomous attribute in multiple ratings. AB - We introduce a sequence of parameters called canonical moments to characterize the predictive value of the pattern of consensus among (kappa-1) ratings to an additional rating. The usual kappa coefficient of agreement among ratings (two or more) is just the second canonical moment. By using the higher canonical moments, we can evaluate the consensus of multiple binary ratings. PMID- 8369389 TI - A test of hypothesis on familial correlations. AB - When familial data are analysed, the model usually employed assumes independence of family observations and constancy of interclass and intraclass correlations. A statistic for testing the validity of the assumptions of family independence and constant interclass and intraclass correlations is developed. The test statistic is for constant family size; it has an asymptotic chi-square distribution. An example to illustrate the theory is given using Frets's data on head lengths. A recommendation is made on how to apply the test to the general case of varying sizes. Another recommendation is made on models to be tried once the null hypothesis is rejected. PMID- 8369390 TI - Nonparametric estimation of relative mortality from nested case-control studies. AB - Andersen et al. (1985, Biometrics 41, 921-932) gave an estimator of the cumulative relative mortality comparing rates of death in an epidemiologic cohort to an external population as a function of time when covariate information is available on all cohort members. We present an analogous estimator when covariate information is known only on a nested case-control sample. Counting process techniques are used to show that this estimator is almost unbiased and an estimator of its variance is derived. Estimators of the relative mortality function, using kernel smoothing methods, and the average relative mortality over grouped time intervals are also presented. The methods are illustrated by comparing rates of lung cancer mortality in a cohort of Montana smelter workers to that in the United States population. PMID- 8369388 TI - On the covariance between parameter estimates in models of twin data. AB - We study the covariance between estimates of additive genetic variance and either dominance genetic variance or common environmental variance in likelihood-based twin analyses. The central tools used in these investigations are the asymptotic covariances of variance component estimates, which we present for several commonly used twin models. We first illustrate the use of the asymptotic covariance terms for determining the optimal ratio of monozygotic to dizygotic group sample sizes for a twin study. We then focus attention on the asymptotic correlations between estimates of additive genetic variance, and either dominance genetic variance or common environmental variance, and their use in understanding when parameters are efficiently estimable from twin data. The results of this investigation are confirmed by simulation studies, and highlight inherent limitations of the twin model, in the sense that having only twin data limits the ability to detect individual variance components. Finally, remarks on possible alternative statistical methods are given, and results are presented to illustrate the improvements in efficiency that are possible with additional family data. In particular, the results provide insight into the limitations of inference from twin data. PMID- 8369391 TI - Nonparametric estimation for the difference or ratio of median failure times. AB - A simple and purely nonparametric confidence interval procedure for the difference or ratio of two median failure times is proposed with censored observations. The new proposal does not involve unstable and complicated nonparametric density estimates and is valid asymptotically even when the two underlying distribution functions differ in shape. Extensive numerical studies are carried out to examine the appropriateness of the new procedure for practical sample sizes. PMID- 8369392 TI - Power and sample size calculations for exact conditional tests with ordered categorical data. AB - We develop an algorithm for computing sample sizes, equal or unequal, for categorical data. We illustrate its use in the two-sample setting using the Wilcoxon rank-sum statistic, but the algorithm accommodates the entire class of linear rank statistics and can be extended to include nonlinear rank statistics as well. The sample size determinations can be based on either exact power or on a very precise Monte Carlo estimate of it. To reduce the computations further, power can be computed as a function of asymptotic critical values when the number of categories is not too small. For the Wilcoxon statistic we show that this approximation works well if there are more than five response categories. PMID- 8369393 TI - An application of the truncated Poisson distribution to immunogold assay. AB - An example of the use of the truncated Poisson distribution in an immunogold assay of dystrophin, a gene product of importance in the study of muscular dystrophies, is presented. The practical benefit of using minimum variance unbiased estimators of relevant functions of the parameter of the distribution is considered. PMID- 8369394 TI - Case studies in binary dispersion. AB - It is common in biomedical studies with binary responses that variability in the observed number of events exceeds binomial variability, a phenomenon known as overdispersion. Failure to make an adjustment to the nominal standard errors can lead to seriously misleading inference for regression analysis. In this note, we examine a series of examples drawn from the literature to see which of two commonly used variance formulas is more adequate for describing overdispersion in applications. Two methods, residual analysis and formal comparison, are introduced. We recommend that both methods be employed in seeking an appropriate variance expression for binary responses. Each of the five data sets exhibits substantial overdispersion, one favoring the beta-binomial form, another favoring a constant overdispersion factor. The remaining three examples exhibit no preference. PMID- 8369395 TI - A test of the missing data mechanism for repeated categorical data. AB - Due to the occurrence of missing observations, longitudinal data are rarely balanced and complete. Weighted least squares analyses described by Grizzle, Starmer, and Koch (1969, Biometrics 25, 489-504) have been developed for the analysis of incomplete longitudinal categorical data [Stanish, Gillings, and Koch (1978, Biometrics 34, 305-317); Woolson and Clarke (1984, Journal of the Royal Statistical Society, Series A 147, 87-99)]. However, all these analyses have assumed that missing observations are missing completely at random in the sense of Rubin (1976, Biometrika 63, 581-592). When the occurrence of missing observations is related to the unobserved response values, these analyses may result in biased results. In this paper, we develop a simple and practical test of the missing mechanism in incomplete repeated categorical data. The proposed test is an extension of the test of Little (1988, Journal of the American Statistical Association 83, 1198-1202) and uses a test criterion given in general form by Wald. The test is illustrated using data from a longitudinal investigation of obesity in school-age children. PMID- 8369396 TI - Comparing proportions in the presence of false positive and false negative instrument sorting errors. PMID- 8369397 TI - Mixture estimation and the neurophysiological quantal hypothesis. AB - Quantal release models provide a mechanistic description of the process by which neurotransmitter is released from the nerve cell. The usual such model assumes that the quantity of transmitter released after nerve depolarization follows a finite mixture distribution with an unknown number of components, and with constraints on component means and variances. General procedures for estimating the dimension of a finite mixture model are discussed, and applied to the analysis of a quantal release data set. PMID- 8369398 TI - How to detect nonrandom motion of proteins in membranes. PMID- 8369399 TI - Calcium on the level. PMID- 8369400 TI - Why pancreatic islets burst but single beta cells do not. The heterogeneity hypothesis. AB - Previous mathematical modeling of beta cell electrical activity has involved single cells or, recently, clusters of identical cells. Here we model clusters of heterogeneous cells that differ in size, channel density, and other parameters. We use gap-junctional electrical coupling, with conductances determined by an experimental histogram. We find that, for reasonable parameter distributions, only a small proportion of isolated beta cells will burst when uncoupled, at any given value of a glucose-sensing parameter. However, a coupled, heterogeneous cluster of such cells, if sufficiently large (approximately 125 cells), will burst synchronously. Small clusters of such cells will burst only with low probability. In large clusters, the dynamics of intracellular calcium compare well with experiments. Also, these clusters possess a dose-response curve of increasing average electrical activity with respect to a glucose-sensing parameter that is sharp when the cluster is coupled, but shallow when the cluster is decoupled into individual cells. This is in agreement with comparative experiments on cells in suspension and islets. PMID- 8369401 TI - Molecular dynamics in lipid bilayers. Anisotropic diffusion in an odd restoring potential. AB - Recent 2H nuclear magnetic resonance spin relaxation studies have questioned the influence of restoring potential parity on the description of lipid or molecular reorientational dynamics. In biomembranes the polar head groups of lipid and sterol constituents are expected to associate with the aqueous interface; therefore, realistic descriptions of molecular reorientation in bilayer systems should use an odd restoring potential. The multiexponential correlation functions and related spectral density functions for small-step anisotropic diffusion in a pseudo-restoring potential of the form U(beta) = -lambda cos beta are evaluated as a function of molecular ordering . From analysis of these results the single exponential approximation used in previous investigations is found to overestimate the decay rate at lower order, but is reliable for > 0.6. The exception to this trend is the decay constant for the G11 (omega; t) correlation function, which is not accurately portrayed by the first order approximations. A second-order single exponential approximation is presented, and is shown to be equivalent to the weighted sum of the multidecay constants. In general, the potential parity is found to have only minor effects on the spin relaxation rates obtained to describe molecular reorientation in lipid bilayers. PMID- 8369403 TI - Weak acid transport across bilayer lipid membrane in the presence of buffers. Theoretical and experimental pH profiles in the unstirred layers. AB - This paper presents a simple model to describe experimental data on weak acid transport across planar bilayer lipid membrane separating two buffered solutions. The model takes into account multiple proton-transfer reactions occurring in the unstirred layers (ULs) adjacent to the membrane. Differential equations of the model are shown to be reduced to a set of nonlinear algebraic equations. Since the latter equations depend monotonically on unknown variables, they can be easily solved numerically, using bisection method. For the particular system studied experimentally (with acetate as the weak acid and TRIS+MES as the buffer mixture) pH profiles in the ULs are calculated from the model. These results are compared with experimental data obtained using pH microelectrode. The agreement between theoretical and experimental pH profiles is found to be satisfactory. The most pronounced deviations are observed at the UL/bulk solution boundary. To obtain a better correlation between the theoretical and experimental results, two other, less idealized models are considered. They take into account, respectively, (a) the electric field arising in the ULs from ion diffusion and (b) finiteness of the rates of proton-transfer reactions. However, both acetate membrane fluxes and pH profiles in the ULs computed from these models are found to be close to those of the simple model. One can thus conclude that the difference between experimental and theoretical pH profiles is due to the inconsistency of the generally accepted model of the "unstirred layer", assuming the existence of a strict boundary between the regions of "pure diffusion" and "ideal stirring". PMID- 8369402 TI - Deformations in the cytoplasmic membrane of Escherichia coli direct the synthesis of peptidoglycan. The hernia model. AB - To explain the growth of the Gram-negative envelope and in particular how it could be strengthened where it is weakest, we propose in the hernia model that local weakening of the peptidoglycan sacculus allows turgor pressure to cause the envelope to bulge outwards in a hernia; the consequent local alteration in the radius of curvature of the cytoplasmic membrane causes local alterations in phospholipid structure and composition that determine both the synthesis and hydrolysis of peptidoglycan. This proposal is supported by evidence that phospholipid composition determines the activity of phospho-N-acetylmuramic acid pentapeptide translocase, UDP-N-acetylglucosamine:N-acetylmuramic acid (pentapeptide)-P-P-bactoprenyl-N-acetylglucosamine transferase, bactoprenyl phosphate phosphokinase, and N-acetylmuramyl-L-alanine amidase. We also propose that the shape of Escherichia coli is maintained by contractile proteins acting at the hernia. Given the universal importance of membranes, these proposals have implications for the determination of shape in eukaryotic cells. PMID- 8369404 TI - Explaining glomerular pores with fiber matrices. A visualization study based on computer modeling. AB - The extracellular space of the glomerular capillary wall is occupied by a complex meshwork of fibrous molecules. Little is understood about how the size, shape, and charge recognition properties of glomerular ultrafiltration arise from this space-filling fiber matrix. We studied the problem of size recognition by visualizing the void volume accessible to hard spheres in computer-generated three-dimensional homogeneous random fiber matrices. The spatial organization of the void volume followed a complex "blob-and-throat" pattern in which circumscribed cavities of free space within the matrix ("blobs") were joined to adjacent cavities by narrower throats of void space. For sufficiently small solutes, chains of blobs and throats traversed the matrix, providing pathways for trans-matrix permeation. The matrices showed threshold or gating properties with respect to permeation: solutes whose radius exceeded a critical value, at which a throat on the last connected trans-matrix pathway pinched off, could not cross, whereas smaller solutes had nonzero permeability. The thresholds may give the glomerular fiber matrix porelike response properties and explain why pore models have been such a useful means of treating permselectivity. PMID- 8369405 TI - Effect of Ca2+ binding on the profile structure of the sarcoplasmic reticulum membrane using time-resolved x-ray diffraction. AB - A number of studies have indicated that Ca(2+)-ATPase, the integral membrane protein of the sarcoplasmic reticulum (SR) membrane, undergoes some structural change upon Ca2+ binding to its high affinity binding sites (i.e., upon conversion of the E1 to the CaxE1 form of the enzyme). We have used x-ray diffraction to study the changes in the electron density profile of the SR membrane upon high-affinity Ca2+ binding to the enzyme in the absence of enzyme phosphorylation. The photolabile Ca2+ chelator DM-nitrophen was used to rapidly release Ca2+ into the extravesicular spaces throughout an oriented SR membrane multilayer and thereby synchronously in the vicinity of the high affinity binding sites of each enzyme molecule in the multilayer. A critical control was developed to exclude possible artifacts arising from heating and non-Ca2+ photolysis products in the membrane multilayer specimens upon photolysis of the DM nitrophen. Upon photolysis, changes in the membrane electron density profile arising from high-affinity Ca2+ binding to the enzyme are found to be localized to three different regions within the profile. These changes can be attributed to the added electron density of the Ca2+ bound at three discrete sites centered at 5, approximately 30, and approximately 67 A in the membrane profile, but they also require decreased electron density within the cylindrically averaged profile structure of the Ca(2+)-ATPase immediately adjacent (< 15 A) to these sites. The locations of these three Ca2+ binding sites in the SR membrane profile span most of the membrane profile in the absence of enzyme phosphorylation,in agreement with the locations of lanthanide (Tb3+ and La3+) binding sites in the membrane profile determined independently by using resonance x-ray diffraction. PMID- 8369406 TI - Eutectic mixed monolayers in equilibrium with phospholipid-bilayers and triolein liquid phase. AB - Triolein (TO) and phospholipids (egg yolk phosphatidylcholine, egg yolk phosphatidylethanolamine, and bovine brain phosphatidylserine) had low mutual solubilities and separated into the TO-liquid phase and phospholipid-bilayers. Spreading pressures of the TO-phospholipid mixture (i.e., surface pressures of the mixed monolayer in equilibrium with the phase-separating lipid mixture) at the air/saline interface were independent of the lipid composition. On the other hand, collapse pressures of the mixed monolayer of TO and phospholipid (i.e., surface pressures of the mixed monolayer in equilibrium with the TO-liquid phase) at the interface changed with the monolayer composition and were lower than the spreading pressure. The experimental data indicated the spreading and collapse pressures as offering a phase diagram for the presence of equilibrium between the mixed monolayer, the phospholipid-bilayers and the TO-liquid phase. The diagram showed that TO and the phospholipids were miscible in the mixed monolayer, forming an eutectic mixed monolayer. When the mixed monolayer initially had the eutectic composition, no collapse of the monolayer was detected until the surface pressure reached the value of the spreading pressure. No specific complex between TO and the phospholipid is required to explain the stability and collapse of the mixed monolayers. The bulk immiscibility of the lipids elucidated by the spreading pressure-measurements, immediately leads to the phase behaviors observed. PMID- 8369407 TI - Lateral diffusion in an archipelago. Single-particle diffusion. AB - Several laboratories have measured lateral diffusion of single particles on the cell surface, and these measurements may reveal an otherwise inaccessible level of submicroscopic organization of cell membranes. Pitfalls in the interpretation of these experiments are analyzed. Random walks in unobstructed systems show structure that could be interpreted as free diffusion, obstructed diffusion, directed motion, or trapping in finite domains. To interpret observed trajectories correctly, one must consider not only the trajectories themselves but also the probabilities of occurrence of various trajectories. Measures of the asymmetry of obstructed and unobstructed random walks are calculated, and probabilities are evaluated for random trajectories that resemble either directed motion or diffusion in a bounded region. PMID- 8369408 TI - Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. AB - Changes in the membrane conductance of sea urchin eggs, during the course of electroporation, were investigated over the time range of 0.5 microsecond to 1 ms by imaging the transmembrane potential at a submicrosecond resolution with the voltage-sensitive fluorescent dye RH292. When a rectangular electric pulse of moderate intensity was applied across an egg, a position-dependent potential developed synchronously with the pulse, as theory predicts for a cell with an insulating membrane. From the rise and fall times, the membrane capacitance of unfertilized eggs was estimated to be 0.95 microF/cm2 and the intracellular conductance 220 omega.cm. Under an electric pulse of much higher intensity, the rise of the induced potential stopped at a certain level and then slowly decreased on the microsecond time scale. This saturation and subsequent reversal of the potential development was ascribed to the introduction of finite membrane conductance, or permeabilization of the membrane, by the action of the intense pulse (electroporation). Detailed analysis indicated the following: already at 0.5 microsecond in the rectangular electric pulse, the two sides of the egg facing the positive and negative electrodes were porated and gave a high membrane conductance in the order of 1 S/cm2; the conductance on the positive side appeared higher. Thereafter, the conductance increased steadily, reaching the order of 10 S/cm2 by 1 ms. This increase was faster on the negative-electrode side; by 1 ms the conductance on the negative side was more than twice that on the positive side. The recovery of the porated membrane after the pulse treatment was assessed from the membrane conductance estimated in a second electric pulse of a small amplitude. At least two recovery processes were distinguished, one with a time constant of 7 microseconds and the other 0.5 ms, at the end of which the membrane conductance was already < 0.1 S/cm2. PMID- 8369409 TI - A mathematically defined motif for the radial distribution of charged residues on apolipoprotein amphipathic alpha helixes. AB - Multiple amphipathic alpha-helical candidate domains have been identified in exchangeable apolipoproteins by sequence analysis and indirect experimental evidence. The distribution of charged residues can differ within and between these apolipoproteins. Segrest et al. (Segrest, J. P., H. DeLoof, J. G. Dohlman, C. G. Brouillette, and G. M. Anantharamaiah. 1990. Proteins. 8:103-117.) argued that these differences are correlated with lipid affinity. A mathematically defined motif for the particular charge distribution associated with high lipid affinity (class A) is proposed. Primary sequence data from protein segments proposed previously to have an amphipathic alpha-helical structure are scanned. Counting formulas are presented for determining the conditional probability that the match between an observed charge distribution and the proposed motif would occur by chance. Because the preselected helical segments are short (the modal length is 22) and the motif definition imposes multiple constraints on the acceptable distributions, the computer-based algorithm is quite feasible computationally. 19 of the 20 segments previously assigned to class A match the motif sufficiently well (the remaining one is borderline), while very few others "erroneously" pass the screening test. These results confirm the original assignments of the candidate domains and, thus, support the hypothesis that there is a distinguishable subset of helixes having high lipid affinity. This counting approach is applicable to a growing subset of protein sequence analysis problems in which the segment lengths are short and the motif is complex. PMID- 8369410 TI - Structural relaxation and nonexponential kinetics of CO-binding to horse myoglobin. Multiple flash photolysis experiments. AB - The geminate recombination kinetics of CO-myoglobin strongly deviates from single exponential behavior in contrast to what is expected for unimolecular reactions (1). At low temperatures, this result was attributed to slowly exchanging conformational states which differ substantially in barrier height for ligand binding. Above 160 K the kinetics apparently slow down with temperature increase. Agmon and Hopfield (2) explain this result in terms of structural relaxation perpendicular to the reaction coordinate, which enhances the activation energy. In their model, structural relaxation homogenizes the kinetic response. Recently, Steinbach et al. (3) proposed a relaxation model which conserves the kinetic inhomogeneity. Below we test these conjectures by single and multiple excitation experiments. This method allows for discrimination between parallel (inhomogeneous) and sequential (homogeneous) kinetic schemes. The kinetic anomaly above 160 K is shown to result from a homogeneous, structurally relaxed intermediate. However a second anomaly is found above 210 K concerning the inhomogeneous phase which may indicate either a shift in activation energy or entropy. PMID- 8369411 TI - A theoretical study of rotational diffusion models for rod-shaped viruses. The influence of motion on 31P nuclear magnetic resonance lineshapes and transversal relaxation. AB - Information about the interaction between nucleic acids and coat proteins in intact virus particles may be obtained by studying the restricted backbone dynamics of the incapsulated nucleic acids using 31P nuclear magnetic resonance (NMR) spectroscopy. In this article, simulations are carried out to investigate how reorientation of a rod-shaped virus particle as a whole and isolated nucleic acid motions within the virion influence the 31P NMR lineshape and transversal relaxation dominated by the phosphorus chemical shift anisotropy. Two opposite cases are considered on a theoretical level. First, isotropic rotational diffusion is used as a model for mobile nucleic acids that are loosely or partially bound to the protein coat. The effect of this type of diffusion on lineshape and transversal relaxation is calculated by solving the stochastic Liouville equation by an expansion in spherical functions. Next, uniaxial rotational diffusion is assumed to represent the mobility of phosphorus in a virion that rotates as a rigid rod about its length axis. This type of diffusion is approximated by an exchange process among discrete sites. As turns out from these simulations, the amplitude and the frequency of the motion can only be unequivocally determined from experimental data by a combined analysis of the lineshape and the transversal relaxation. In the fast motional region both the isotropic and the uniaxial diffusion model predict the same transversal relaxation as the Redfield theory. For very slow motion, transversal relaxation resembles the nonexponential relaxation as observed for water molecules undergoing translational diffusion in a magnetic field gradient. In this frequency region T2e is inversely proportional to the cube root of the diffusion coefficient. In addition to the isotropic and uniaxial diffusion models, a third model is presented, in which fast restricted nucleic acid backbone motions dominating the lineshape are superimposed on a slow rotation of the virion about its length axis, dominating transversal relaxation. In an accompanying article the models are applied to the 31P NMR results obtained for bacteriophage M13 and tobacco mosaic virus. PMID- 8369412 TI - Analysis of 31P nuclear magnetic resonance lineshapes and transversal relaxation of bacteriophage M13 and tobacco mosaic virus. AB - The experimentally observed 31P lineshapes and transversal relaxation of 15% (wt/wt) M13, 30% M13, and 30% tobacco mosaic virus (TMV) are compared with lineshapes and relaxation curves that are simulated for various types of rotational diffusion using the models discussed previously (Magusin, P. C. M. M., and M. A. Hemminga. 1993. Biophys. J. 64:1851-1860). It is found that isotropic diffusion cannot explain the observed lineshape effects. A rigid rod diffusion model is only successful in describing the experimental data obtained for 15% M13. For 30% M13 the experimental lineshape and relaxation curve cannot be interpreted consistently and the TMV lineshape cannot even be simulated alone, indicating that the rigid rod diffusion model does not generally apply. A combined diffusion model with fast isolated motions of the encapsulated nucleic acid dominating the lineshape and a slow overall rotation of the virion as a whole, which mainly is reflected in the transversal relaxation, is able to provide a consistent picture for the 15 and 30% M13 samples, but not for TMV. Strongly improved lineshape fits for TMV are obtained assuming that there are three binding sites with different mobilities. The presence of three binding sites is consistent with previous models of TMV. The best lineshapes are simulated for a combination of one mobile and two static sites. Although less markedly, the assumption that two fractions of DNA with different mobilities exist within M13 also improves the simulated lineshapes. The possible existence of two 31P fractions in M13 sheds new light on the nonintegral ratio 2.4:1 between the number of nucleotides and protein coat subunits in the phage: 83% of the viral DNA is less mobile, suggesting that the binding of the DNA molecule to the protein coat actually occurs at the integral ratio of two nucleotides per protein subunit. PMID- 8369413 TI - Temperature dependence of the phosphorescence quantum yield of various alpha lactalbumins and of hen egg-white lysozyme. AB - The radiative quantum yield, phi op, of the triplet state of human alpha lactalbumin (HLA) has been measured in the temperature range between 6 K and the softening point of the aqueous glass (approximately 150 K). phi op has little temperature dependence below approximately 30 K, but above this it decreases sharply with increasing temperature. The unusual temperature dependence is fitted by a phenomenological two-state model in which the phosphorescence originates primarily from a donor, tryptophan (Trp) 104, and an acceptor, Trp 60, the populations of which are coupled by a thermally activated triplet-triplet energy transfer process. The model assumes that the acceptor (Trp 60) triplet state undergoes radiationless deactivation by a proximal disulfide residue, while the donor (Trp 104) has no such extrinsic quencher. The decrease of phi op with increasing temperature is accounted for by the thermally activated triplet triplet energy transfer process. The disulfide quenching rate constant itself is assumed to be temperature independent, in accord with recent measurements of simple disulfide quenching in long chain snake venom neurotoxins (Schlyer, B. D., E. Lau, and A. H. Maki. 1992. Biochemistry. 31:4375-4383; Li, Z., A. Bruce, and W. C. Galley. 1992. Biophys. J. 61:1364-1371). We find that the phosphorescence quenching in HLA occurs with an activation energy of 97 cm-1, which we associate with a barrier to the energy transfer process. The data are fit well by the model if we assume a value for the temperature-independent disulfide quenching constant of kQ > 3 s-1 that is consistent with recent measurements on indole-disulfide model systems (Li, Z., A. Bruce, and W. C. Galley. 1992. Biophys. J. 61:1364 1371). Similar results are reported for bovine alpha-lactalbumin (BLA) and for hen egg-white lysozyme (HEWL) that contains the structural equivalents of Trp 104 and Trp 60 of HLA. HLA provides the best agreement with calculations since it is the simplest, lacking Trp 26, a residue not considered in the model, that probably contributes significantly to the phosphorescence of BLA, guinea pig alpha-lactalbumin (GPLA), and HEWL. GPLA, which contains Trp 104 but lacks Trp 60, shows qualitatively less thermally induced phosphorescence quenching than HLA, BLA, and HEWL, thus supporting the postulated quenching model. PMID- 8369414 TI - Nonequilibrium freezing of one-cell mouse embryos. Membrane integrity and developmental potential. AB - A thermodynamic model was used to evaluate and optimize a rapid three-step nonequilibrium freezing protocol for one-cell mouse embryos in the absence of cryoprotectants (CPAs) that avoided lethal intracellular ice formation (IIF). Biophysical parameters of one-cell mouse embryos were determined at subzero temperatures using cryomicroscopic investigations (i.e., the water permeability of the plasma membrane, its temperature dependence, and the parameters for heterogeneous IIF). The parameters were then incorporated into the thermodynamic model, which predicted the likelihood of IIF. Model predictions showed that IIF could be prevented at a cooling rate of 120 degrees C/min when a 5-min holding period was inserted at -10 degrees C to assure cellular dehydration. This predicted freezing protocol, which avoided IIF in the absence of CPAs, was two orders of magnitude faster than conventional embryo cryopreservation cooling rates of between 0.5 and 1 degree C/min. At slow cooling rates, embryos predominantly follow the equilibrium phase diagram and do not undergo IIF, but mechanisms other than IIF (e.g., high electrolyte concentrations, mechanical effects, and others) cause cellular damage. We tested the predictions of our thermodynamic model using a programmable freezer and confirmed the theoretical predictions. The membrane integrity of one-cell mouse embryos, as assessed by fluorescein diacetate retention, was approximately 80% after freezing down to -45 degrees C by the rapid nonequilibrium protocol derived from our model. The fact that embryos could be rapidly frozen in the absence of CPAs without damage to the plasma membrane as assessed by fluorescein diacetate retention is a new and exciting finding. Further refinements of this protocol is necessary to retain the developmental competence of the embryos. PMID- 8369415 TI - Use of fura red as an intracellular calcium indicator in frog skeletal muscle fibers. AB - Fura red, a fluorescent Ca2+ indicator with absorbance bands at visible wavelengths, was injected into intact single muscle fibers that had been stretched to a long sarcomere length (approximately 3.8 microns) and bathed in a 'high-Ca2+' Ringer ([Ca2+] = 11.8 mM). From fura red's slow diffusion coefficient in myoplasm, 0.16 (+/- 0.01, SEM) x 10(-6) cm2 s-1 (N = 5; 16 degrees C), it is estimated that approximately 85% of the indicator molecules are bound to muscle constituents of large molecular weight. Binding appears to elevate, by 3- to 4 fold, the indicator's apparent dissociation constant for Ca2+ (KD), which is estimated to be 1.1-1.6 microM in myoplasm. Fura red's myoplasmic absorbance spectrum was used to estimate fr, the fraction of fura red molecules in the Ca2+ bound form at rest. In 3 fibers thought to be minimally damaged by the micro injection, fr was estimated to be 0.15 (+/- 0.01). Thus, resting myoplasmic free [Ca2+] ([Ca2+]r) is estimated to be 0.19-0.28 microM. For fibers in normal Ringer solution ([Ca2+] = 1.8 mM), at shorter sarcomere length (approximately 2.7 microns), and containing a nonperturbing concentration of indicator (< or = 0.2 mM), [Ca2+]r is estimated to be 0.18-0.27 microM. This range is higher than estimated previously in frog fibers with other techniques. In 6 fibers, R, the indicator's fluorescence ratio signal (equal to the emission intensity measured with 420 nm excitation divided by that measured with 480 nm excitation), was measured at rest and following electrical stimulation and compared with absorbance measurements made from the same fiber region. The analysis implies that RMIN and RMAX (the values of R that would be measured if all indicator molecules were in the Ca(2+)-free and Ca(2+)-bound states, respectively) were substantially smaller in myoplasm than in calibration solutions lacking muscle proteins. Several methods for estimation of [Ca2+]r from R are analyzed and discussed. PMID- 8369417 TI - Bending rigidity of SOPC membranes containing cholesterol. AB - Bilayer membranes in the fluid state exhibit a large resistance to changes in surface area, negligible resistance to surface shear deformation, and a small but finite resistance to bending. The presence of cholesterol in the membrane is known to increase its resistance to area dilation. In this report, a new method for measuring bilayer membrane bending stiffness has been used to investigate the effect of cholesterol on the bending rigidity of SOPC (1,stearoyl-2,oleoyl phosphatidylcholine) membranes. The curvature elasticity (kc) for membranes saturated with cholesterol was measured to be 3.3 x 10(-19) J, approximately 3 fold larger than that the modulus for cholesterol-free SOPC membrane. These findings are consistent with previous measurements of bending stiffness based on thermal fluctuations, which showed a similar approximately 3-fold increase in the modulus with cholesterol addition (Evans and Rawicz, 1990, Phys. Rev. Lett. 64:2094) and provide further substantiation of the important contribution that cholesterol makes to membrane cohesion and stability. PMID- 8369416 TI - Human olfactory neurons respond to odor stimuli with an increase in cytoplasmic Ca2+. AB - The sense of smell allows terrestrial animals to collect information about the chemical nature of their environment through the detection of airborne molecules. In humans smell is believed to play an important role in protecting the organism from environmental hazards such as fire, gas leaks and spoiled food, in determining the flavor of foods, and perhaps in infant-parent bonding. In addition, the study of human olfaction is relevant to a number of medical problems that result in olfactory dysfunction, which can affect nutritional state, and to the study of the etiology of neurodegenerative diseases which manifest themselves in the olfactory epithelium. Although much is known about behavioral aspects of human olfaction, little is understood about the underlying cellular mechanisms in humans. Here we report that viable human olfactory neurons (HON) can be isolated from olfactory tissue biopsies, and we find that HON respond to odorants with an increase in intracellular calcium concentration ([Cai]). PMID- 8369418 TI - The effects of bilirubin on the thermal properties of phosphatidylcholine bilayers. AB - The thermotropic properties of multilamellar vesicles of dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), and distearoylphosphatidylcholine (DSPC), as a function of the concentration of bilirubin in the range of 0.1 to 1 mol%, were measured. The exact effects of bilirubin depended on the chain length of the polymethylene chains. But the general effects of bilirubin were the same in all systems. At the lowest concentrations tested (0.1 mol bilirubin/100 mol phospholipid (0.1 mol%)), bilirubin broadened and shifted to higher temperatures the main phase transitions of all bilayers. For DPPC and DSPC, but not DMPC, this concentration of bilirubin was associated with a new transition at 25 degrees C (DPPC) or 34 degrees C (DSPC). Bilirubin at 0.2 mol% was required for the detection of a similar transition (at 13.7 degrees C) in DMPC. Higher concentrations of bilirubin (> 0.2 mol%) suppressed completely the main phase transitions in all bilayers but increased the enthalpy of the new transition. Maximal values of delta H for these transitions were reached at 0.5, 0.25, and 0.2 mol% bilirubin in DMPC, DPPC, and DSPC, respectively. Values of delta H and delta S for these transitions were far larger than for the corresponding gel-to-liquid crystal transitions in pure lipid bilayers but were equal to those expected for a transition between crystalline and liquid crystalline phases. PMID- 8369419 TI - Tracing charge separation events in photosynthesis: anomalous photovoltage polarity events explained. PMID- 8369421 TI - Estimated acid dissociation constants of the Schiff base, Asp-85, and Arg-82 during the bacteriorhodopsin photocycle. AB - The pK(a) values of D85 in the wild-type and R82Q, as well as R82A recombinant bacteriorhodopsins, and the Schiff base in the D85N, D85T, and D85N/R82Q proteins, have been determined by spectroscopic titrations in the dark. They are used to estimate the coulombic interaction energies and the pK(a) values of the Schiff base, D85, and R82 during proton transfer from the Schiff base to D85, and the subsequent proton release to the bulk in the initial part of the photocycle. The pK(a) of the Schiff base before photoexcitation is calculated to be in effect only 5.3-5.7 pH units higher than that of D85; overcoming this to allow proton transfer to D85 requires about two thirds of the estimated excess free energy retained after absorption of a photon. The proton release on the extracellular surface is from an unidentified residue whose pK(a) is lowered to about 6 after deprotonation of the Schiff base (Zimanyi, L., G. Varo, M. Chang, B. Ni, R. Needleman, and J.K. Lanyi, 1992. Biochemistry. 31:8535-8543). We calculate that the pK(a) of the R82 is 13.8 before photoexcitation, and it is lowered after proton exchange between the Schiff base and D85 only by 1.5-2.3 pH units. Therefore, coulombic interactions alone do not appear to change the pK(a) of R82 as much and D85 only by 1.5-2.3 pH units. Therefore, coulombic interactions alone do not appear to change the pK(a) of R82 as much as required if it were the proton release group. PMID- 8369420 TI - Cooperativity in F-actin: chemical modifications of actin monomers affect the functional interactions of myosin with unmodified monomers in the same actin filament. AB - We have chemically modified a fraction of the monomers in actin filaments, and then measured the effects on the functional interaction of myosin with unmodified monomers within the same filament. Two modifications were used: (a) covalent attachment of various amounts of myosin subfragment-1 (S1) with the bifunctional reagent disuccinimidyl suberate and (b) copolymerization of unmodified actin monomers with monomers cross-linked internally with 1-ethyl-3 (dimethylaminopropyl)-carbodiimide. Each of these modifications abolished the interaction of the modified monomers with myosin, so the remaining interactions were exclusively with unmodified monomers. The two modifications had similar effects on the interaction of actin with myosin in solution: decreased affinity of myosin heads for unmodified actin monomers, without a change in the Vmax of actin-activated myosin ATPase activity. However, modification (b) produced much greater inhibition of actin sliding on a myosin-coated surface, as measured by an in vitro motility assay. These results provide insight into the functional consequences of cooperative interactions within the actin filament. PMID- 8369422 TI - Glycerol effects on protein flexibility: a tryptophan phosphorescence study. AB - In exploring the dynamic properties of protein structure, numerous studies have focussed on the dependence of structural fluctuations on solvent viscosity, but the emerging picture is still not well defined. Exploiting the sensitivity of the phosphorescence lifetime of tryptophan to the viscosity of its environment we have used the delayed emission as an intrinsic probe of protein flexibility and investigated the effects of glycerol as a viscogenic cosolvent. The phosphorescence lifetime of alcohol dehydrogenase, alkaline phosphatase, apoazurin and RNase T1, as a function of glycerol concentration was studied at various temperatures. Flexibility data, which refer to rather rigid sites of the globular structures, point out that, for some concentration ranges glycerol, effects on the rate of structural fluctuations of alcohol dehydrogenase and RNase T1 do not obey Kramers' a power law on solvent viscosity and emphasize that cosolvent-induced structural changes can be important, even for inner cores of the macromolecule. When the data is analyzed in terms of Kramers' model, for the temperature range 0-30 degrees C one derives frictional coefficients that are relatively large (0.6-0.7) for RNase T1, where the probe is in a flexible region near the surface of the macromolecule and much smaller, less than 0.2, for the rigid sites of the other proteins. For the latter sites the frictional coefficient rises sharply between 40 and 60 degrees C, and its value correlates weakly with molecular parameters such as the depth of burial or the rigidity of a particular site. For RNase T1, coupling to solvent viscosity increases at subzero temperatures, with the coefficient becoming as large as 1 at -20 degrees C. Temperature effects were interpreted by proposing that solvent damping of internal protein motions is particularly effective for low frequency, large amplitude, structural fluctuations yielding highly flexible conformers of the macromolecule. PMID- 8369423 TI - The relationship of agarose gel structure to the sieving of spheres during agarose gel electrophoresis. AB - To understand the organization of fibers in an agarose gel, digitized electron micrographs are used here to determine the frequency distribution of interfiber distance (2Pc) in thin sections of agarose gels. For a preparation of underivatized agarose, a 1.5% gel has a Pc distribution that is indistinguishable from the Pc distribution of a computer-generated, random-fiber gel; the log of the occurrence frequency (F) decreases linearly as a function of Pc. As the agarose concentration decreases below 1.5%, the semilogarithmic F versus Pc plot becomes progressively less linear. Two straight lines represent the data; the plot is steeper at the lower Pc values. As the percentage of agarose increases above 1.5%, the semilogarithmic F versus Pc plot becomes steeper at the higher Pc values. This change in the shape of semilogarithmic F versus Pc plots is possibly explained by the existence in agarose gels of two zones, one whose Pc distribution is more sensitive to the average agarose concentration than the other. To compare the structure of agarose gels to their sieving during electrophoresis, the root mean square value of Pc (Pc) is compared to the sieving based radius of the effective pore (PE; Griess et. al. (16)) for both underivatized agarose and a derivatized agarose that has a smaller PE at any given agarose percentage. For 0.8-2.0% gels of either underivatized or derivatized agarose, PE/Pc is a constant within experimental error. Deviations from this constant are observed at lower gel percentages. This relationship of PE to Pc constrains theoretical descriptions of the motion of spheres in fibrous networks. PMID- 8369424 TI - Transients in neuron with arbitrary dendritic branching and shunted soma. PMID- 8369425 TI - The binding capacity is a probability density function. AB - The binding capacity of a system, or equivalently, the fluctuations of the number of ligands bound around the average value defined by the binding isotherm, can be regarded as a probability density function for the chemical potential of the ligand. The first moment of this density function is the mean ligand activity as defined by Wyman and gives the average free energy (in kT units) of binding per site. The second moment is directly related to the cooperativity of the system. These and higher moments can be obtained from numerical integration of experimental data in a direct way. An analytical expression for the moment generating function shows that the N independent coefficients of the partition function of a system containing N sites are uniquely defined by the first N moments of the binding capacity. PMID- 8369427 TI - Zippier zaps: faster electrostatics calculations. PMID- 8369426 TI - Single event recording shows that docking onto receptor alters the kinetics of membrane fusion mediated by influenza hemagglutinin. AB - The initial steps of membrane fusion, receptor binding and membrane destabilization, are mediated by the envelope glycoprotein hemagglutinin of influenza virus. Interaction between these functions was determined from the time course of individual virion fusions to a planar membrane with and without receptor. With receptor, fusion was described by a Poisson process. In the absence of receptor, the time course was more complicated and could not be described with exponential rate constants. The conversion of a non-Markovian process into a simple Markov chain is direct evidence that receptor binding fundamentally alters the route of fusion. PMID- 8369428 TI - NADH fluorescence of isolated ventricular myocytes: effects of pacing, myoglobin, and oxygen supply. AB - Endogenous fluorescence was used to measure the extent of reduction of mitochondrial NAD in individual, isolated rat cardiac myocytes. NAD reduction was determined from emitted fluorescence at 415 and 470 nm during brief epi illumination at 365 nm. NAD reduction of resting myocytes, superfused with medium equilibrated with 95% O2/5% CO2, was 27 +/- 3% (SE) (n = 78), comparable to that in beating whole heart. Increasing intracellular Ca2+ did not significantly change NAD reduction. NAD reduction decreased reversibly to 11 +/- 1% (n = 78) in contracting myocytes electrically paced at 5 Hz for 10 min. Oxygen uptake was stimulated fivefold. There was minimal change in sarcoplasmic pH measured by fluorescence of carboxy-seminaphthorhodafluor-1. However, NAD reduction increased reversibly in response to electrically paced contractions when: (a) myoglobin was inactivated with sodium nitrite (37 +/- 7%; n = 48); or (b) cells were more densely layered and gassed with 20% O2/5% CO2 (48 +/- 3%; n = 30). We conclude that (a) the ratio NADH/NAD is decreased in well-oxygenated cells with increased work; (b) steady-state NAD reduction is increased with increased work when oxygen delivery is limited; and (c) functional myoglobin ensures an oxygen supply to the mitochondria of working cells. PMID- 8369429 TI - The changing faces of research. PMID- 8369430 TI - Affinity of alpha-actinin for actin determines the structure and mechanical properties of actin filament gels. AB - Proteins that cross-link actin filaments can either form bundles of parallel filaments or isotropic networks of individual filaments. We have found that mixtures of actin filaments with alpha-actinin purified from either Acanthamoeba castellanii or chicken smooth muscle can form bundles or isotropic networks depending on their concentration. Low concentrations of alpha-actinin and actin filaments form networks indistinguishable in electron micrographs from gels of actin alone. Higher concentrations of alpha-actinin and actin filaments form bundles. The threshold for bundling depends on the affinity of the alpha-actinin for actin. The complex of Acanthamoeba alpha-actinin with actin filaments has a Kd of 4.7 microM and a bundling threshold of 0.1 microM; chicken smooth muscle has a Kd of 0.6 microM and a bundling threshold of 1 microM. The physical properties of isotropic networks of cross-linked actin filaments are very different from a gel of bundles: the network behaves like a solid because each actin filament is part of a single structure that encompasses all the filaments. Bundles of filaments behave more like a very viscous fluid because each bundle, while very long and stiff, can slip past other bundles. We have developed a computer model that predicts the bundling threshold based on four variables: the length of the actin filaments, the affinity of the alpha-actinin for actin, and the concentrations of actin and alpha-actinin. PMID- 8369431 TI - Blitz and blizzard: crossbridges and chaos. PMID- 8369432 TI - Time-resolved fluorescence of the single tryptophan of Bacillus stearothermophilus phosphofructokinase. AB - The fluorescence of the single tryptophan in Bacillus stearothermophilus phosphofructokinase was characterized by steady-state and time-resolved techniques. The enzyme is a tetramer of identical subunits, which undergo a concerted allosteric transition. Time-resolved emission spectral data were fitted to discrete and distributed lifetime models. The fluorescence decay is a double exponential with lifetimes of 1.6 and 4.4 ns and relative amplitudes of 40 and 60%. The emission spectra of both components are identical with maxima at 327 nm. The quantum yield is 0.31 +/- 0.01. The shorter lifetime is independent of temperature; the longer lifetime has weak temperature dependence with activation energy of 1 kcal/mol. The fluorescence intensity and decay are the same in H2O and D2O solutions, indicating that the indole ring is not accessible to bulk aqueous solution. The fluorescence is not quenched significantly by iodide, but it is quenched by acrylamide with bimolecular rate constant of 5 x 10(8) M-1 s-1. Static and dynamic light scattering measurements show that the enzyme is a tetramer in solution with hydrodynamic radius of 40 A. Steady-state and time resolved fluorescence anisotropies indicate that the tryptophan is immobile. The allosteric transition has little effect on the fluorescence properties. The fluorescence results are related to the x-ray structure. PMID- 8369433 TI - Conformational transformations in the protein lattice of phage P22 procapsids. AB - During the packaging of double-stranded DNA by bacterial viruses, the precursor procapsid loses its internal core of scaffolding protein and undergoes a substantial expansion to form the mature virion. Here we show that upon heating, purified P22 procapsids release their scaffolding protein subunits, and the coat protein lattice expands in the absence of any other cellular or viral components. Following these processes by differential scanning calorimetry revealed four different transitions that correlated with structural transitions in the coat protein shells. Exit of scaffolding protein from the procapsid occurred reversibly and just above physiological temperature. Expansion of the procapsid lattice, which was exothermic, occurred after the release of scaffolding protein. Partial denaturation of coat subunits within the intact shell structure was detected prior to the major endothermic event. This major endotherm occurred above 80 degrees C and represents particle breakage and irreversible coat protein denaturation. The results indicate that the coat subunits are designed to form a metastable precursor lattice, which appears to be separated from the mature lattice by a kinetic barrier. PMID- 8369434 TI - Probability of alamethicin conductance states varies with nonlamellar tendency of bilayer phospholipids. AB - With few exceptions, membrane lipids are usually regarded as a kind of filler or passive solvent for membrane proteins. Yet, cells exquisitely control membrane composition. Many phospholipids found in plasma membrane bilayers favor packing into inverted hexagonal bulk phases. It was suggested that the strain of forcing such lipids into a bilayer may affect membrane protein function, such as the operation of transmembrane channels. To investigate this, we have inserted the peptide alamethicin into bilayer membranes composed of lipids of empirically determined inverted hexagonal phase "spontaneous radii" Ro, which will have expectably different degrees of strain when forced into bilayer form. We observe a correlation between measured Ro and the relative probabilities of different conductance states. States of higher conductance are more probable in dioleoylphosphatidylethanolamine, the lipid of highest curvature, 1/Ro, than in dioleoylphosphatidylcholine, the lipid of lowest curvature. PMID- 8369435 TI - A novel fluorescence ratiometric method confirms the low solvent viscosity of the cytoplasm. AB - Two homologous indocyanine dyes, Cy3.18 and Cy5.18, can be used as a ratio pair for fluorometric determination of solvent viscosity. Succinimidyl ester derivatives of these dyes can be attached to inert carrier macromolecules, such as Ficoll 70, for measurement of intracellular or intravesicular solvent viscosity. When the viscosity of the solvent was varied by various methods, the fluorescence intensity ratio (Cy3/Cy5) in a mixture of Cy3.18-Ficoll 70 (Cy3F70) and Cy5.18-Ficoll 70 (Cy5F70) in solution was found to be solely a function of solvent viscosity and was insensitive to other solvent parameters such as dielectric constant, temperature, and the ability of the solvent to form hydrogen bonds. Most important, it was insensitive to the presence of large macromolecules, such as proteins, which increase the shear viscosity but have little effect on solvent viscosity. Following microinjection into the cytoplasm of living tissue culture cells, no binding of Cy3F70 or Cy5F70 to intracellular components was detected by fluorescence recovery after photobleaching. Fluorescence intensity ratio imaging of Cy3F70 and Cy5F70 in non-motile interphase CV1 and PtK1 cells showed that the solvent viscosity of cytoplasm was not significantly different from water and showed no spatial variation. PMID- 8369436 TI - Transition modes in Ising networks: an approximate theory for macromolecular recognition. AB - For a statistical lattice, or Ising network, composed of N identical units existing in two possible states, 0 and 1, and interacting according to a given geometry, a set of values can be found for the mean free energy of the 0-->1 transition of a single unit. Each value defines a transition mode in an ensemble of nu N = 3N - 2N possible values and reflects the role played by intermediate states in shaping the energetics of the system as a whole. The distribution of transition modes has a number of intriguing properties. Some of them apply quite generally to any Ising network, regardless of its dimension, while others are specific for each interaction geometry and dimensional embedding and bear on fundamental aspects of analytical number theory. The landscape of transition modes encapsulates all of the important thermodynamic properties of the network. The free energy terms defining the partition function of the system can be derived from the modes by simple transformations. Classical mean-field expressions can be obtained from consideration of the properties of transition modes in a rather straightforward way. The results obtained in the analysis of the transition mode distributions have been used to develop an approximate treatment of the problem of macromolecular recognition. This phenomenon is modeled as a cooperative process that involves a number of recognition subsites across an interface generated by the binding of two macromolecular components. The distribution of allowed binding free energies for the system is shown to be a superposition of Gaussian terms with mean and variance determined a priori by the theory. Application to the analysis of the biologically interaction of thrombin with hirudin has provided some useful information on basic aspects of the interaction, such as the number of recognition subsites involved and the energy balance for binding and cooperative coupling among them. Our results agree quite well with information derived independently from analysis of the crystal structure of the thrombin-hirudin complex. PMID- 8369437 TI - Measuring orientation of actin filaments within a cell: orientation of actin in intestinal microvilli. AB - Orientational distribution of actin filaments within a cell is an important determinant of cellular shape and motility. To map this distribution we developed a method of measuring local orientation of actin filaments. In this method actin filaments within cells are labeled with fluorescent phalloidin and are viewed at high magnification in a fluorescent microscope. Emitted fluorescence is split by a birefringent crystal giving rise to two images created by light rays polarized orthogonally with respect to each other. The two images are recorded by a high sensitivity video camera, and polarization of fluorescence at any point is calculated from the relative intensity of both images at this point. From the value of polarization, the orientation of the absorption dipole of the dye, and thus orientation of F-actin, can be calculated. To illustrate the utility of the method, we measured orientation of actin cores in microvilli of chicken intestinal epithelial cells. F-actin in microvillar cores was labeled with rhodamine-phalloidin; measurements showed that the orientation was the same when microvillus formed a part of a brush border and when it was separated from it suggesting that "shaving" of brush borders did not distort microvillar structure. In the absence of nucleotide, polarization of fluorescence of actin cores in isolated microvilli was best fitted by assuming that a majority of fluorophores were arranged with a perfect helical symmetry along the axis of microvillus and that the absorption dipoles of fluorophores were inclined at 52 degrees with respect to the axis. When ATP was added, the shape of isolated microvilli did not change but polarization of fluorescence decreased, indicating statistically significant increase in disorder and a change of average angle to 54 degrees. We argue that these changes were due to mechanochemical interactions between actin and myosin-I. PMID- 8369438 TI - Solid state NMR study of [epsilon-13C]Lys-bacteriorhodopsin: Schiff base photoisomerization. AB - Previous solid state 13C-NMR studies of bacteriorhodopsin (bR) have inferred the C = N configuration of the retinal-lysine Schiff base linkage from the [14 13C]retinal chemical shift (1-3). Here we verify the interpretation of the [14 13C]-retinal data using the [epsilon-13C]lysine 216 resonance. The epsilon-Lys 216 chemical shifts in bR555 (48 ppm) and bR568 (53 ppm) are consistent with a C = N isomerization from syn in bR555 to anti in bR568. The M photointermediate was trapped at pH 10.0 and low temperatures by illumination of samples containing either 0.5 M guanidine-HCl or 0.1 M NaCl. In both preparations, the [epsilon 13C]Lys-216 resonance of M is 6 ppm downfield from that of bR568. This shift is attributed to deprotonation of the Schiff base nitrogen and is consistent with the idea that the M intermediate contains a C = N anti chromophore. M is the only intermediate trapped in the presence of 0.5 M guanidine-HCl, whereas a second species, X, is trapped in the presence of 0.1 M NaCl. The [epsilon-13C]Lys-216 resonance of X is coincident with the signal for bR568, indicating that X is either C = N anti and protonated or C = N syn and deprotonated. PMID- 8369439 TI - Cellular motions and thermal fluctuations: the Brownian ratchet. AB - We present here a model for how chemical reactions generate protrusive forces by rectifying Brownian motion. This sort of energy transduction drives a number of intracellular processes, including filopodial protrusion, propulsion of the bacterium Listeria, and protein translocation. PMID- 8369440 TI - Fluorescence dequenching kinetics of single cell-cell fusion complexes. AB - In an earlier paper which models the cell-cell (or virus-cell) fusion complex as two partial spherical vesicles joined at a narrow neck (Rubin, R. J., and Yi-der Chen. 1990. Biophys. J. 58:1157-1167), the redistribution by diffusion of lipid like molecules through the neck between the two fused cell surfaces was studied. In this paper, we extend the study to the calculation of the kinetics of fluorescence increase in a single fusion complex when the lipid-like molecules are fluorescent and self-quenching. The formalism developed in this paper is useful in deducing fusion activation mechanisms from cuvette fluorescence measurements in cell-cell fusion systems. Two different procedures are presented: 1) an exact one which is based on the exact local density functions obtained from diffusion equations in our earlier study; and 2) an approximate one which is based on treating the kinetics of transfer of probes between the two fused cells as a two-state chemical reaction. For typical cell-cell fusion complexes, the fluorescence dequencing curves calculated from the exact and approximate procedures are very similar. Due to its simplicity, the approximate method should be very useful in future applications. The formalism is applied to a typical cell cell fusion complex to study the sensitivity of dequenching curves to changes in various fusion parameters, such as the radii of the cells, the radius of the pore at the fusion junction, and the number of probes initially loaded to the complex. PMID- 8369441 TI - Aggregation and disaggregation kinetics of human blood platelets: Part I. Development and validation of a population balance method. AB - Hydrodynamic shear stress of sufficient intensity is known to cause platelet activation and aggregation and to alter the effects of biochemical platelet agonists and antagonists. In this work, a population balance equation (PBE) model is developed for analysis of platelet aggregation and disaggregation kinetics under the influence of a shear field. The model incorporates both aggregation and disaggregation by splitting and/or erosion mechanisms. This paper, the first of a series of three, deals with the formulation, simplification, and validation of the PBE and with the estimation of parameters involved in the PBE. These population parameters include collision efficiency, void fraction (related to the particle collision diameter), and the breakage rate coefficient. The platelet particle size distribution is determined experimentally, both initially and at some later times. The PBE can then be used to match satisfactorily the observed particle histograms, by appropriate choice of parameters of the model as functions of time, platelet size, and magnitude of physical or chemical stimuli. Besides providing information on adhesive forces and on the rates of aggregation and disaggregation, these parameters infer the physical properties of platelets and platelet aggregates. These properties are of potential value in increasing our understanding of the processes involved in thrombotic disease and/or therapy. A numerical procedure for solving the PBE is validated by application to simple cases for which analytical solutions are available. The model is applied to analysis of experiments, and parameter sensitivity studies are used to order the importance of the parameters and to reduce the complexity of the model. The simplified model is shown to give good agreement with experimental observations. PMID- 8369442 TI - Aggregation and disaggregation kinetics of human blood platelets: Part II. Shear induced platelet aggregation. AB - A population balance equation (PBE) mathematical model for analyzing platelet aggregation kinetics was developed in Part I (Huang, P. Y., and J. D. Hellums. 1993. Biophys. J. 65: 334-343) of a set of three papers. In this paper, Part II, platelet aggregation and related reactions are studied in the uniform, known shear stress field of a rotational viscometer, and interpreted by means of the model. Experimental determinations are made of the platelet-aggregate particle size distributions as they evolve in time under the aggregating influence of shear stress. The PBE model is shown to give good agreement with experimental determinations when either a reversible (aggregation and disaggregation) or an irreversible (no disaggregation) form of the model is used. This finding suggests that for the experimental conditions studied disaggregation processes are of only secondary importance. During shear-induced platelet aggregation, only a small fraction of platelet collisions result in the binding together of the involved platelets. The modified collision efficiency is approximately zero for shear rates below 3000 s-1. It increases with shear rates above 3000 s-1 to about 0.01 for a shear rate of 8000 s-1. Addition of platelet chemical agonists yields order of magnitude increases in collision efficiency. The collision efficiency for shear-induced platelet aggregation is about an order of magnitude less at 37 degrees C than at 24 degrees C. The PBE model gives a much more accurate representation of aggregation kinetics than an earlier model based on a monodispersed particle size distribution. PMID- 8369443 TI - Aggregation and disaggregation kinetics of human blood platelets: Part III. The disaggregation under shear stress of platelet aggregates. AB - In the preceding two papers (1, 2), a population balance equation (PBE) mathematical model was developed, validated, and applied to the analysis of platelet aggregation kinetics under the influence of hydrodynamic shear stress. The present work involves the application of the model to the analysis of platelet reactions under shear stress in circumstances where disaggregation processes are of dominant importance: the disaggregation of aggregates formed in response to added agonists. Aggregation-disaggregation experiments were performed in the constant shear field of a rotational viscometer, and the evolution of the particle size distribution was determined by use of an electronic particle counter. The PBE model was used to simulate the experimental results. Exploratory calculations made it possible to reduce a rather complete, complex model to a more tractable form which retains the capability of simulating the experimental observations. For the experimental conditions studied, disaggregation by a splitting mechanism was found to be of dominant importance. The surface erosion mechanism can be neglected without significant impact on results. Physical reasoning confirmed by exploratory calculations showed that a discontinuous form of the breakage rate expression which incorporates a minimum friable particle size, gives significantly better results than a continuous expression. A simple step function void fraction parameter was found to be at least as successful as a more complicated, continuous function. The resulting simplified model has the potential of increasing our understanding of kinetics and mechanisms of platelet reactions, and of characterizing the state of platelet activity. Hence, it may be useful in efforts to understand thrombotic and hemostatic processes. PMID- 8369444 TI - Why does the light-gradient photovoltage from photosynthetic organelles show a wavelength-dependent polarity? AB - The light-gradient photovoltage from photosynthetic organisms and organelles is thought to arise from the primary charge separation in the reaction centers. The current explanation of the effect is the stronger excitation of the membrane side of a vesicle facing the light source than the one on the opposite side. Together with the known orientation of reaction centers, this explanation predicts unequivocally the polarity of the photovoltage. However, a polarity opposite to the one expected has often been reported. A dependence of the polarity on the wavelength has been published but no explanation was given (Graber, P., and H.-W. Trissl. 1981. FEBS Lett. 123:95-99). Here we report on a theoretical treatment of light propagation and interference in pigmented and nonpigmented multilayers. A model calculation is carried out for a pair of membranes, demonstrating the wavelength-dependent light distribution as well as the relative photovoltage and its polarity. When the membranes contain no chromophores or when the absorption coefficient is low, the predicted polarity to that expected from a simple macroscopic absorption behavior. The model is tested by comparing new photovoltage data obtained at 532 nm as well as in the blue and red absorption bands of chlorophyll in chloroplasts. It is concluded that outside the main absorption bands the amplitude and polarity of the photovoltage is determined by the ratio of the refractive indices of the membrane and the medium. PMID- 8369445 TI - Flash and smash: rapid freezing of muscle fibers activated by photolysis of caged ATP. AB - A new approach was used to study transient structural states of cross-bridges during activation of muscle fibers. Rabbit skinned muscle fibers were rapidly and synchronously activated from the rigor state by photolysis of caged ATP in the presence of Ca2+. At several different times during the switch from rigor to fully active tension development, the fibers were rapidly frozen on a liquid helium-cooled metal block, freeze-substituted, and examined in an electron microscope. The limits of structural preservation and resolution with this technique were analyzed. We demonstrate that the resolution of our images is sufficient to draw the following conclusions about cross-bridge structure. Rigor cross-bridges point away from the Z-line and most of them are wider near the thin filaments than near the backbone of the thick filaments. In contrast, cross bridges in actively contracting fibers stretch between the thick and thin filaments at a variable angle, and are uniformly thin. Diffraction patterns computed from contracting muscle show layer lines both at 38 and 43 nm indicating that active cross-bridges contribute mass to both the actin- and myosin-based helical periodicities. The images obtained from fibers frozen 20 ms after release of ATP show a mixture of rigor and active type cross-bridge configurations. There is little evidence of cross-bridges with the rigor shape by 50 ms, and the difference in configurations between 50 and 300 ms after photolysis is surprisingly subtle. PMID- 8369446 TI - An experimental evaluation of the critical potential difference inducing cell membrane electropermeabilization. AB - When applied on intact cell suspension, electric field pulses are known to induce membrane permeabilization (electropermeabilization) and fusion (electrofusion). These effects are triggered through a modulation of the membrane potential difference. Due to the vectorial character of the electric field effects, this modulation, which is superimposed on the resting membrane potential difference, is position-dependent on the cell surface. This explains the difference between the experimentally observed critical field strengths requested to trigger the processes of permeabilization and fusion. The critical membrane potential difference which induces membrane permeabilization can be calculated from these experimental observations. It is observed that its value is always about 200 mV for many different cell systems as we previously reported in the case of pure lipid vesicles. This is much less than assumed in most previous studies. PMID- 8369447 TI - Solutions for transients in arbitrarily branching cables: I. Voltage recording with a somatic shunt. AB - An analytical solution is derived for voltage transients in an arbitrarily branching passive cable neurone model with a soma and somatic shunt. The response to injected currents can be represented as an infinite series of exponentially decaying components with different time constants and amplitudes. The time constants of a given model, obtained from the roots of a recursive transcendental equation, are independent of the stimulating and recording positions. Each amplitude is the product of three factors dependent on the corresponding root: one constant over the cell, one varying with the input site, and one with the recording site. The amplitudes are not altered by interchanging these sites. The solution reveals explicitly some of the parameter dependencies of the responses. An efficient recursive root-finding algorithm is described. Certain regular geometries lead to "lost" roots; difficulties associated with these can be avoided by making small changes to the lengths of affected segments. Complicated cells, such as a CA1 pyramid, produce many closely spaced time constants in the range of interest. Models with large somatic shunts and dendrites of unequal electrotonic lengths can produce large amplitude waveform components with surprisingly slow time constants. This analytic solution should complement existing passive neurone modeling techniques. PMID- 8369448 TI - The nature of cation-pi binding: interactions between tetramethylammonium ion and benzene in aqueous solution. AB - A combined quantum mechanical and molecular mechanical Monte Carlo simulation method was used to determine the free energy of binding between tetramethylammonium ion (TMA+) and benzene in water. The computed free energy as a function of distance (the potential of mean force) has two minima that represent contact and solvent-separated complexes. These species are separated by a broad barrier of about 3 kJ/mol. The results are in good accord with experimental data and suggest that TMA+ binds to benzene more favorably than to chloride ion, with an association constant of about 0.8 M-1. PMID- 8369449 TI - Solutions for transients in arbitrarily branching cables: II. Voltage clamp theory. AB - Analytical solutions are derived for arbitrarily branching passive neurone models with a soma and somatic shunt, for synaptic inputs and somatic voltage commands, for both perfect and imperfect somatic voltage clamp. The solutions are infinite exponential series. Perfect clamp decouples different dendritic trees at the soma: each exponential component exists only in one tree; its time constant is independent of stimulating and recording position within the tree; its amplitude is the product of a factor constant over that entire tree and factors dependent on stimulating and recording positions. Imperfect clamp to zero is mathematically equivalent to voltage recording with a shunt. As the series resistance increases, different dendritic trees become more strongly coupled. A number of interesting response symmetries are evident. The solutions reveal parameter dependencies, including an insensitivity of the early parts of the responses to specific membrane resistivity and somatic shunt, and an approximately linear dependence of the slower time constants on series resistance, for small series resistances. The solutions are illustrated using a "cartoon" representation of a CA1 pyramidal cell and a two-cylinder + soma model. PMID- 8369450 TI - Solutions for transients in arbitrarily branching cables: III. Voltage clamp problems. AB - Branched cable voltage recording and voltage clamp analytical solutions derived in two previous papers are used to explore practical issues concerning voltage clamp. Single exponentials can be fitted reasonably well to the decay phase of clamped synaptic currents, although they contain many underlying components. The effective time constant depends on the fit interval. The smoothing effects on synaptic clamp currents of dendritic cables and series resistance are explored with a single cylinder + soma model, for inputs with different time courses. "Soma" and "cable" charging currents cannot be separated easily when the soma is much smaller than the dendrites. Subtractive soma capacitance compensation and series resistance compensation are discussed. In a hippocampal CA1 pyramidal neurone model, voltage control at most dendritic sites is extremely poor. Parameter dependencies are illustrated. The effects of series resistance compound those of dendritic cables and depend on the "effective capacitance" of the cell. Plausible combinations of parameters can cause order-of-magnitude distortions to clamp current waveform measures of simulated Schaeffer collateral inputs. These voltage clamp problems are unlikely to be solved by the use of switch clamp methods. PMID- 8369451 TI - Multigrid solution of the nonlinear Poisson-Boltzmann equation and calculation of titration curves. AB - Although knowledge of the pKa values and charge states of individual residues is critical to understanding the role of electrostatic effects in protein structure and function, calculating these quantities is challenging because of the sensitivity of these parameters to the position and distribution of charges. Values for many different proteins which agree well with experimental results have been obtained with modified Tanford-Kirkwood theory in which the protein is modeled as a sphere (reviewed in Ref. 1); however, convergence is more difficult to achieve with finite difference methods, in which the protein is mapped onto a grid and derivatives of the potential function are calculated as differences between the values of the function at grid points (reviewed in Ref. 6). Multigrid methods, in which the size of the grid is varied from fine to coarse in several cycles, decrease computational time, increase rates of convergence, and improve agreement with experiment. Both the accuracy and computational advantage of the multigrid approach increase with grid size, because the time required to achieve a solution increases slowly with grid size. We have implemented a multigrid procedure for solving the nonlinear Poisson-Boltzmann equation, and, using lysozyme as a test case, compared calculations for several crystal forms, different refinement procedures, and different charge assignment schemes. The root mean square difference between calculated and experimental pKa values for the crystal structure which yields best agreement with experiment (1LZT) is 1.1 pH units, with the differences in calculated and experimental pK values being less than 0.6 pH units for 16 out of 21 residues. The calculated titration curves of several residues are biphasic. PMID- 8369452 TI - Effect of stress on the membrane capacitance of the auditory outer hair cell. AB - The membrane capacitance of the outer hair cell, which has unique membrane potential-dependent motility, was monitored during application of membrane tension. It was found that the membrane capacitance of the cell decreased when stress was applied to the membrane. This result is the opposite of stretching the lipid bilayer in the plasma membrane. It thus indicates the importance of some other capacitance component that decreases on stretching. It has been known that charge movement across the membrane can appear to be a nonlinear capacitance. If membrane stress at the resting potential restricts the movement of the charge associated with force generation, the nonlinear capacitance will decrease. Furthermore, less capacitance reduction by membrane stretching is expected when the membrane is already extended by the (hyperpolarizing) membrane potential. Indeed, it was found that at hyperpolarized potentials, the reduction of the membrane capacitance due to stretching is less. The capacitance change can be described by a two state model of a force-producing unit in which the free energy difference between the contracted and stretched states has both electrical and mechanical components. From the measured change in capacitance, the estimated difference in the membrane area of the unit between the two states is about 2 nm2. PMID- 8369453 TI - Simulations of three-dimensional ciliary beats and cilia interactions. AB - A new set of equations describing the time evolution of torsion and curvature for an inextensible curve is developed. Combined with our recently developed Slender Body Theory approach to such problems, these equations were applied to simulate three-dimensional ciliary beats, while allowing for cilia interactions. The computer animation technique, which was originally designed to display two dimensional beats, has been enhanced to accommodate the new three-dimensional results. PMID- 8369454 TI - Conformational change--an alternative energy source? Exothermic phase transition in phage capsid maturation. PMID- 8369455 TI - Comparative study of phototactic and photophobic receptor chromophore properties in Chlamydomonas reinhardtii. AB - The motile, unicellular, eukaryotic alga Chlamydomonas reinhardtii exhibits two distinct behavioral reactions to light stimuli, phototaxis and the photophobic response. Both are mediated by retinal-containing receptors. This paper focuses on a direct comparison of the two photoresponses and the chromophore requirements for their photoreceptor(s). Using computerized motion analysis assays for phototaxis and photophobic responses by the same populations of cells, we measured the ability of various isomers and analogues of retinal to reconstitute photobehavior in the pigment-deficient mutant FN68. The results indicate that photophobic and phototaxis responses each require chromophores with an all-trans polyene chain configuration, planar ionone ring/polyene chain conformation, and the ability to isomerize around the retinal C13-C14 double bond. One difference between the two behaviors is that the photophobic response becomes highly desensitized after light stimuli to which the phototaxis response does not become desensitized, indicating the existence of at least one distinct step in the photophobic response pathway. A second difference is that the retinal regeneration of the photophobic response but not of phototaxis is inhibited by a 5-membered ring 13-trans-locked analogue. While showing close similarity in the chromophore structural requirements of the two behaviors, the results indicate that differences exist between the two responses at the level of their photoreceptor proteins and/or in their transduction processes. PMID- 8369456 TI - Reconstruction of ionic currents in a molluscan photoreceptor. AB - Two-microelectrode voltage-clamp measurements were made to determine the kinetics and voltage dependence of ionic currents across the soma membrane of the Hermissenda type B photoreceptor. The voltage-dependent outward potassium currents, IA and ICa(2+)-K+, the inward voltage-dependent calcium current, ICa2+ and the light-induced current, IIgt, were then described with Hodgkin-Huxley-type equations. The fast-activating and inactivating potassium current, IA, was described by the equation; IA(t) = gA(max)(ma infinity[1-exp(-t/tau ma)])3 x (ha infinity [1-exp(-t/tau ha)] + exp(-t/tau ha)) (Vm-EK), where the parameters ma infinity, ha infinity, tau ma, and tau ha are functions of membrane potential, Vm, and ma infinity and ha infinity are steady-state activation and inactivation parameters. Similarly, the calcium-dependent outward potassium current, ICa(2+) K+, was described by the equation, ICa(2+)-K+ (t) = gc(max)(mc infinity(VC)(1 exp[-t/tau mc (VC)]))pc (hc infinity(VC) [1-exp(-t/tau hc)] + exp(-t/tau hc(VC)])pc(VC-EK). In high external potassium, ICa(2+)-K+ could be measured in approximate isolation from other currents as a voltage-dependent inward tail current following a depolarizing command pulse from a holding potential of -60 mV. A voltage-dependent inward calcium current across the type B soma membrane, ICa2+, activated rapidly, showed little inactivation, and was described by the equation: ICa2+ = gCa(max) [1 + exp](-Vm-5)/7]-1 (Vm-ECa), where gCa(max) was 0.5 microS. The light-induced current with both fast and slow phases was described by: IIgt(t) = IIgt1 + IIgt2 + IIgt3, IIgti = gIgti [1-exp(- ton/tau mi)] exp( ton/tau hi)(Vm-EIgti) (i = 1, 2). For i = 3, /Igt(t) = gigt3m33h3(Vm - Eigt3)exp( ton/Ton) x exp(-tfoff/t Off). Based on these reconstructions of ionic currents, learning-induced enhancement of the long lasting depolarization (LLD) of the photoreceptor'slight response was shown to arise from progressive inactivation of /A, lca2+ -K+, and lCa2+. PMID- 8369457 TI - Bioelectrorheological model of the cell. 4. Analysis of the extensil deformation of cellular membrane in alternating electric field. AB - Analysis of the angular distribution of extensil mechanical stress, sigma e, generated in cytoplasmic membranes by an external oscillating electric field, is presented. Theoretical considerations show that sigma e is directly proportional to the local relative increase in membrane area and/or to the local relative decrease in its thickness. The magnitude of this stress depends on the position of the analyzed point of the membrane in relation to field direction. The maximal value, sigma eo, is reached at the cell "poles." The magnitude of sigma eo depends on electric and geometric parameters (in particular on field frequency) of the system studied. The foregoing analysis can be applied to quantitatively describe the destabilizing effects of the electric field on the cellular membrane, leading to its poration, fusion, and destruction. PMID- 8369458 TI - Bioelectrorheological model of the cell. 5. Electrodestruction of cellular membrane in alternating electric field. AB - Recently proposed analysis of the extensil stress developed in a cellular membrane subjected to an alternating electric field (Pawlowski, P., and M. Fikus, 1993. Bioelectrorheological model of the cell. 4. Analysis of the extensil deformation of the membrane in an alternating field. Biophys. J. 65:535-540) was applied in calculations of extensil stress threshold values, sigma eo[d], producing experimentally observed electrodestruction of cells within the frequency range of 7 x 10(1) - 3 x 10(5) Hz. It was shown that the susceptibility (s[d] = 1/sigma eo[d]), of the membrane to this process varies with field frequency and depends on the type of cells. Electrodestruction is facilitated in the 10(5)-Hz field. A rheological hypothesis explaining the experimentally observed dependence of membrane stability on electric field frequency was proposed and successfully tested for two other phenomena: electroporation and electrofusion. PMID- 8369459 TI - Mesophase transition temperatures as measured by fluorescence and calorimetry. PMID- 8369460 TI - Teaching biophysics. Strategies for recruiting and retaining minorities in physics and biophysics. AB - Several strategies directed toward increasing the participation of minority students in physics and biophysics are presented. Since the number of minority students entering college with an interest in science and mathematics must be increased if we expect to see more students graduating in science, several programs aimed at increasing the level of instruction of physics and biology in urban middle schools and high schools are outlined. We also describe approaches designed to increase the retention of science major during the freshman core physics course where many potential science majors are lost. Increasing the number of minority students at the PhD level will rely increasingly on partnerships between research universities and historically black colleges and universities (HBCUs) and several programs already in effect are given as examples of such linkages. PMID- 8369462 TI - Fusion flashes illuminate kinetics. PMID- 8369461 TI - Supramolecular ordering of DNA in the cholesteric liquid crystalline phase: an ultrastructural study. AB - Aqueous solutions of 146-base pair DNA fragments form a cholesteric liquid crystalline phase in the range of about 160-290 mg/ml. We present a structural analysis of this phase by comparing the data obtained from polarizing and electron microscopy. This phase shows multiple aspects or "textures" which are presented and interpreted. They mainly depend on the orientation of the structure relative to the observation plane and on the nature, distribution, and amount of defects present in the phase. These defects are then analyzed with the two methods, and the molecular orientations can be defined precisely in their core. The biological interest of such structural analyses is discussed in relation with the understanding of chromatin structure and function. PMID- 8369463 TI - How does a virus bud? AB - How does a virus bud from the plasma membrane of its host? Here we investigate several possible rate-limiting processes, including thermal fluctuations of the plasma membrane, hydrodynamic interactions, and diffusion of the glycoprotein spikes. We find that for bending moduli greater than 3 x 10(-13) ergs, membrane thermal fluctuations are insufficient to wrap the viral capsid, and the mechanical force driving the budding process must arise from some other process. If budding is limited by the rate at which glycoprotein spikes can diffuse to the budding site, we compute that the budding time is 10-20 min, in accord with the experimentally determined upper limit of 20 min. In light of this, we suggest some alternative mechanisms for budding and provide a rationale for the observation that budding frequently occurs in regions of high membrane curvature. PMID- 8369464 TI - Understanding fluorescence decay in proteins. PMID- 8369465 TI - Myocardial dysfunction following cardiopulmonary bypass: recovery patterns, predictors of inotropic need, theoretical concepts of inotropic administration. AB - Clinical myocardial dysfunction following cardiopulmonary bypass commonly occurs in patients with good preoperative ventricular function. Following separation from cardiopulmonary bypass, ventricular function improves initially, but then begins to worsen and reaches a nadir between 4 and 6 hours after surgery with full recovery occurring around 24 hours postoperatively. However, in patients with preoperative ventricular dysfunction, the depression of ventricular function is more severe and recovery is longer. Despite this high frequency of myocardial dysfunction, many patients do well without requiring pharmacologic intervention after cardiopulmonary bypass to augment contractility and peripheral perfusion. Factors that may predict the need for inotropic support in patients following cardiopulmonary bypass include low ejection fraction, older age, cardiac enlargement, female sex, the length of cardiopulmonary bypass and the duration of aortic cross-clamping. The patient with preoperative ventricular dysfunction has many of these preoperative and intraoperative predictors for inotropic support. The pharmacologic regimen to support the myocardium during the recovery period following cardiopulmonary bypass must take into consideration the pathophysiologic processes of chronic congestive heart failure and reperfusion injury. Reduction of cyclic adenosine monophosphate (cAMP) levels is a fundamental problem in congestive heart failure and results from either down regulation of beta-receptors or a defect in the G-regulatory proteins controlling adenylyl cyclase production. This diminishes the effectiveness of agents dependent on cAMP to produce an inotropic response. However, amplification of the reduced cAMP produced by beta-agonists may occur in association with the inhibition of cAMP breakdown resulting from phosphodiesterase inhibitors. All inotropic agents are usually effective in reversing the reperfusion-induced stunned myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369466 TI - Congestive heart failure: systolic and diastolic function. AB - There is increasing recognition that disorders of both left ventricular systolic and diastolic function can result in congestive heart failure. As such, consideration of both the filling and emptying characteristics of the left heart is needed to evaluate the hemodynamic abnormalities present in this syndrome. Considerations of the systolic (emptying) and diastolic (filling) pumping characteristics of the left heart also provides a conceptual basis to classify and understand the pathophysiology of congestive heart failure. In this context, systolic dysfunction can be defined as impaired emptying of the LV, apparent as a decreased (< 50%) effective ejection fraction (forward stroke volume divided by end-diastolic volume). Systolic dysfunction may result from impaired myocardial contractile function, increased left ventricular afterload, and/or structural abnormalities of the left heart. Diastolic dysfunction can be defined as a condition in which filling of the LV sufficient to produce an adequate cardiac output requires an elevated pulmonary venous pressure. Thus, diastolic dysfunction is clinically manifested as pulmonary congestion. Defined in this manner, the most common cause of diastolic dysfunction is systolic dysfunction. In fact, the most common symptom of patients with systolic dysfunction is dyspnea from the resulting diastolic dysfunction. Diastolic dysfunction in the setting of normal systolic function may be due to obstruction of left ventricular filling, impaired left ventricular distensibility, or extensive external compression of the LV. Treatment of diastolic dysfunction can be accomplished by relieving myocardial ischemia, improving systolic function, lowering arterial systolic pressure, and decreasing cardiac distention. PMID- 8369467 TI - Early intervention of inotropic support in facilitating weaning from cardiopulmonary bypass: the New England Deaconess Hospital experience. AB - The current article reviews the therapeutic advantages and disadvantages of early inotropic intervention prior to separation from cardiopulmonary bypass (CPB). Background information is provided on predictors of failure to wean as well as the multiple etiologies and consequences of the "failed wean" from CPB. Advantages of early inotropic intervention include (1) increased contractility, (2) resolution/prevention of ischemia, (3) attainment of therapeutic levels of drug, (4) minimization of inotropic side effects while on CPB, (5) avoidance of mechanical intervention (intra-aortic balloon pump), (6) dilatation of the internal mammary artery, and (7) prevention of the "failed wean". Disadvantages of early inotropic intervention include (1) unnecessary drug usage, (2) tachycardia/arrhythmias, (3) hyper/hypotension, (4) metabolic disturbances (hyperglycemia), (5) coagulation disorders, (6) need for additional drugs to treat side effects, (7) possible myocardial damage, and (8) additional costs. A brief review of this institution's preference for amrinone follows, including its pharmacology, side effects, and dosing prior to separation from CPB. Due to the large percentage of patients with diabetes mellitus undergoing cardiac surgery at our institution (approximately 30% to 40%) a synopsis of special inotropic considerations for this patient population is included. PMID- 8369468 TI - Support of the perioperative failing heart with preexisting ventricular dysfunction: currently available options. AB - Perioperative support of the patient with preexisting biventricular failure requires simultaneous optimal manipulation of heart rate and rhythm, loading conditions, and contractility. Patients with preexisting ventricular dysfunction will have alterations in beta-adrenergic receptors, resulting in decreased responsiveness to catecholamines. Even patients with previously normal ventricular function can develop ventricular dysfunction caused by reperfusion injury and other potentially damaging effects of extracorporeal circulation. The mainstay of therapeutic agents used to allow separation from cardiopulmonary bypass are catecholamines, which stimulate alpha- and beta-adrenergic receptors. Submaximal responses to beta 1-adrenergic stimulation can occur in the down regulated heart. The phosphodiesterase inhibitors provide both inotropic support and vasodilatation, which improves both systolic and diastolic function and bypasses beta-adrenergic receptors. When administered in combination, catecholamine and cyclic-AMP-specific phosphodiesterase inhibitors can have additive effects to restore beta 1-adrenergic responsiveness. Combination therapy provides an important therapeutic option to facilitate separation from cardiopulmonary bypass. Pharmacologic intervention for right ventricular dysfunction focuses on reversal of pulmonary vasoconstriction with nitrates, beta 2-adrenergic agents, phosphodiesterase inhibitors and prostaglandin E1. PMID- 8369469 TI - Postcardioplegia acute cardiac dysfunction and reperfusion injury. AB - In cardiac surgery, an obligatory period of ischemia is imposed in order to provide a convenient operative field. Brief periods of ischemia produce systolic and diastolic abnormalities related to pathology occurring during ischemia per se (ischemic injury) or expressed after the onset of reperfusion (reperfusion injury). In the surgical setting, ischemia may be encountered preoperatively with preexisting coronary disease, hypotension, or ventricular fibrillation, between intermittent infusions of cardioplegia solutions, or as a result of maldistribution of cardioplegia solution. The potential for reperfusion injury exists not only at the time of cross-clamp removal, but also with each infusion of cardioplegia solution. Infusion of cardioplegic solution is, in fact, a form of reperfusion to previously ischemic myocardium. Ischemic injury and reperfusion injury are intimately linked in that the severity of ischemia sets the stage for and determines, in part, the extent of reperfusion injury. Mild-to-moderate systolic dysfunction, which may be called "postcardioplegia stunning," remains a significant complication after cardiac surgery. More significant postoperative functional depression may occur in hearts with severe preoperative dysfunction, and in operations requiring long cross-clamp times. In addition, the failure to adequately distribute cardioplegic solution to all areas of the myocardium because of coronary stenoses, high coronary resistance or inadequate delivery pressure-flow relations, contributes to postcardioplegia dysfunction. However, the cardioplegic solution itself may also contribute to postcardioplegic dysfunction by creating temporary ionic and metabolic abnormalities. In addition, systemic hypocalcemia or hyperkalemia resulting from using large doses of cardioplegic solution may temporarily aggravate postcardioplegic mechanical dysfunction. Current formulations and strategies for delivery of cardioplegia solutions are designed to address the various contributors to both ischemic and reperfusion injury that may impact on postoperative mechanical performance. Ischemic injury is avoided by reducing myocardial oxygen demand by engaging immediate arrest and cooling the heart to approximately 10 degrees centigrade, and intermittently infusing solution to reoxygenate the myocardium, maintain hypothermia, and wash out accumulated metabolites. Reperfusion injury may be avoided by infusing hyperosmotic solutions at moderate pressures, and by incorporating oxygen radical scavengers or inhibitors to reduce membrane lipid peroxidation, myocellular and microcirculatory (endothelium) damage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8369470 TI - Alzheimer's disease and spirochetes; a questionable relationship. PMID- 8369471 TI - Alzheimer's disease--a spirochetosis? AB - The aetiology of Alzheimer's disease (AD), which affects a large proportion of the aged population is unknown and the treatment unresolved. The role of beta amyloid protein (beta A4), derived from a larger amyloid precursor protein (APP) in AD is the subject of intense research. Here I report observations that in 14 autopsy cases with histopathologically confirmed AD, spirochetes were found in blood and cerebrospinal fluid and, moreover, could be isolated from brain tissue. Thirteen age-matched control cases were without spirochetes. Reference strains of spirochetes and those isolated from brains of AD patients, showed positive immunoreaction with monoclonal antibody against the beta amyloid precursor protein. These observations suggest that spirochetes may be one of the causes of AD and that they may be the source of the beta amyloid deposited in the AD brain. PMID- 8369472 TI - The peptidergic motoneurone. AB - Acetylcholine is the classic transmitter in the spinal cord motoneurone. Recent studies have shown that motoneurones also contain calcitonin-gene related peptide (CGRP) and other peptides. In addition to transmitter-like effects, CGRP may also exert trophic actions, as suggested by changes in CGRP expression in motoneurones during development and following experimental perturbations. PMID- 8369474 TI - Lesions of the hippocampus enhance or depress humoral immunity in rats. AB - The effect on the humoral immune response in rats by bilaterally destroying cell bodies in the hippocampus with kainic acid or by electrolytic lesion was studied. After 3 days a humoral immune response was evoked by injecting 1 ml of 10% sheep red blood cells. Five days later, the haemolysin content (MC50) was measured. Chemical destruction of pyramidal cell bodies in CA2 and CA3 significantly increased humoral immunity as measured by HC50, but larger chemical lesions that also included CA1 did not. Electrical destruction of cell bodies and axonal pathways in CA2 and CA3 did not significantly affect HC50. These results suggest that different areas of the hippocampus can stimulate or inhibit humoral immunity. PMID- 8369473 TI - Second messenger-induced modulation of the excitability of respiratory neurones. AB - The phospholipase inhibitor quinacrine and the protein kinase C activator phorbol 12,13-dibutyrate were injected intracellularly into expiratory neurones of the ventral respiratory group within the brain stem of anaesthetized cats. Neurones were identified by their on-going spontaneous respiratory activity and by antidromic excitation from the spinal cord at the C2-C3 level. Phorbol-12,13 dibutyrate and quinacrine, increased the amplitude of respiratory drive potentials reproducing an effect which is also obtained by potassium blockers. We conclude that modulation accounts for approximately a 40% reduction of the excitatory respiratory drive potentials provided by the respiratory rhythm generator. This modulation appears to be mediated by potassium currents that are controlled by intracellular messengers in brain stem respiratory neurones. PMID- 8369475 TI - Sensory receptor-like cells in the human foetal vomeronasal organ. AB - The vomeronasal organ (VNO) was studied in ten human foetuses, 12 to 36 weeks old. At 12 to 23 weeks, it was lined by a smooth pseudostratified epithelium, with neurone-specific enolase (NSE) positive cells looking like olfactory receptors. Clusters of NSE-positive cells were seen in relation with the posterosuperior end of the organ and along nerve fascicles in the nasal septum. At 36 weeks, the organ was lined by a respiratory epithelium and did not show any receptor-like cells; some pear-shaped NSE-positive cells of unknown significance were seen at the upper part of the respiratory epithelium. Our results suggest that during the early foetal period, the VNO could have some, as yet unknown, sensory function. PMID- 8369476 TI - Pheromones induce c-fos in limbic areas regulating male hamster mating behavior. AB - Hamsters rely on chemosensory cues from females of the same species for the initiation of copulatory behavior. While these cues are detected by both the main and accessory olfactory systems it is the central nuclei in the accessory system that regulate mating behavior. The results of the present study indicate that exposure to vaginal secretions from a female Syrian hamster (FHVS) stimulates c fos production in the medial nucleus of the amygdala (Me), the bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA). Exposure to vaginal secretions from Djungarian hamsters do not stimulate neurons in these areas. Thus the present results suggest that FHVS stimulates mating behavior by activating neurons within the vomeronasal pathway. PMID- 8369477 TI - Hip stabilization and lateral balance control in toddlers during the first four months of autonomous walking. AB - The main purpose of the present paper was to investigate the inter-segmental coordinations between hip, shoulder and head, in toddlers, during the first four months of autonomous walking. The efficiency of locomotor balance control was examined in the frontal plane. The main result to emerge from this study is that the hip stabilization in space appears as soon as the first week of autonomous walking, while shoulder stabilization in space appears to be effective only at the second month. Finally, no preferred head stabilization, either in space or on shoulders, has appeared by the end of the fourth month. These results seem to indicate, from an early hip stabilization, an ascending progression with age of the ability to control lateral balance during locomotion. PMID- 8369478 TI - Lesion of the suprasylvian cortex impairs depth perception of cats. AB - Using a 2-alternative-forced-choice-procedure on a jumping stand, four adult cats were trained to make simple depth discriminations. They were tested binocularly and monocularly before and after bilateral lesions of different parts of the lateral suprasylvian cortex. Our results give support to a functional segregation between the lateral suprasylvian visual areas (LSA) and area 7. Lesion of any of these areas impairs the ability to use binocular depth cues. However, lesion of LSA more severely impairs the ability to use monocular depth cues whereas binocular ones can still be used. After lesion of area 7, binocular depth cues can no longer be used. Additional undercutting of areas 17/18/19 leads to a performance similar to that of area 17/18 lesioned cats. PMID- 8369479 TI - Is water diffusion restricted in human brain white matter? An echo-planar NMR imaging study. AB - Water diffusion is extremely anisotropic in brain white matter, depending on myelin fiber orientation. A suggested, but unproven cause of anisotropy is that, in the direction transverse to the myelin fibers, axonal water diffusion is prevented by the presence of the myelin sheath. We found, however, using an ultra fast nuclear magnetic resonance imaging technique, that the dependence of the diffusion coefficient on the diffusion time does not support the model of water restriction by impenetrable barriers. These results, which were obtained non invasively in vivo in the human brain, imply that water diffuses with a measurable rate across myelin fibers. PMID- 8369480 TI - Transient expression of PKC gamma mRNA in cerebellar granule cells during rat brain development. AB - The localization of PKC gamma mRNA expression during the maturation of rat cerebellum has been studied by in situ hybridization. We found a transient expression over the granule cell layer and persistent high expression in the Purkinje cells during postnatal development. Expression in granule cells appeared as early as postnatal day 5 over the external granule cell layer, when Purkinje cells are multiply innervated by climbing fibres in contrast to their mono innervation in the adult. As the regression of the poly-innervation during the following weeks is known to require granule cell input, our findings suggest that the PKC gamma expression over the migrating granule cell layer is linked to the process of selective stabilization of synapses during the maturation of the cerebellum. PMID- 8369481 TI - Oral stimulations induce apnoea in newborn kittens. AB - The aim of the present work was to study oral trigeminal mechanisms which might induce apnoeic reflexes in adult cats and kittens at different postnatal ages. Various oral stimulations and electrical stimulations of the lingual nerve produced apnoeas whose duration decreased with age until three weeks of life. In addition, swallowing was only rarely observed before 5 days and then occurred with apnoea until the third week. Responses became similar to those observed in adults between weeks 3 and 4. Thus, in kittens, the nervous control which regulates coordination between breathing and swallowing appears to be immature at birth. PMID- 8369482 TI - Cell migration and subplate loss in explant cultures of murine cerebral cortex. AB - We studied whether cortical cells migrate and subplate cells are lost in explants of murine cortex cultured for up to 14 days in defined serum-free medium. We gave bromodeoxyuridine (BrdU) to mice on embryonic days 12-13 (E12-13), to label subplate cells, or E17, to label cells destined for superficial cortical layers. We started culturing on E18-20. We left some mice to develop and provide in vivo data. At E18-20, most cells born on E17 lay below the cortical plate. During the following days in vitro, many of them moved to the cortical plate's superficial edge, although an abnormally high number remained in the ventricular zone. There was a selective loss of BrdU labelled cells from the subplate in culture; this occurred more rapidly than in vivo. Factors absent from our cultures may normally enhance migration and prolong the survival of subplate cells. PMID- 8369483 TI - Activation of PKC reverses apparent NMDA receptor reduction in ALS. AB - The binding of [3H]MK-801 to NMDA receptors was reduced by 40-45% in the dorsal and ventral horns of spinal cords from patients who died with amyotrophic lateral sclerosis (ALS) compared with controls. These results reflect either neurone death with concomitant receptor loss or regulation-related receptor decreases independent of motoneurone degeneration. To distinguish between these possibilities we explored aspects of NMDA receptor regulation using phorbol ester to activate protein kinase C (PKC). Spinal cord sections were exposed to phorbol ester before incubation with [3H]MK-801 to determine levels of NMDA binding. Phorbol ester treatment increased [3H]MK-801 binding in both ALS and control tissue to almost identical levels of specific binding for both groups. The increased [3H]MK-801 binding could be completely blocked by concurrent exposure of spinal cord sections to H-7, a general protein kinase inhibitor. These results suggest that NMDA receptors in ALS spinal cord are decreased as a result of abnormal enzyme activity independent of motoneurone degeneration. PMID- 8369484 TI - Endothelin-1-like immunoreactivity is expressed in human reactive astrocytes. AB - The expression of endothelin-1-like immunoreactivity in astrocytes of the human brain was investigated by the avidin-biotin-peroxidase complex method in post mortem material. A marked immunoreaction was present in reactive astrocytes around infarcts, lacunes, traumatic injuries, the lesions of progressive multifocal leuco-encephalopathy and in the cerebral cortex and white matter of Alzheimer's disease. The brains of patients who had neither history nor signs of cerebral disease exhibited only occasional immunoreactive astrocytes. A hypothesis is presented that endothelin-1 may be released from reactive astrocytes in many organic diseases of the human brain with considerable pathogenic consequences. It is known from experimental investigations that endothelin-1 may for instance cause severe vasoconstriction resulting in cell injury and that it may act as a growth factor for glial cells. PMID- 8369485 TI - N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of dextromethorphan in rats. AB - The present study examined whether the antitussive agent dextromethorphan, which is an antagonist at the N-methyl-D-aspartate (NMDA) receptor, depresses spinal reflexes in rats. Injection of both the specific NMDA antagonist (-)-2-amino-7 phosphonoheptanoate and of dextromethorphan dose-dependently reduced the magnitude of the polysynaptic flexor reflex without affecting the monosynaptic H reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of dextromethorphan on the flexor reflex was prevented by co-administration with NMDA but not with the non-NMDA agonist alpha amino-3-hydroxy-5-terthyl-4-isoxazole-propionic acid. These data suggest that dextromethorphan exerts a muscle relaxant action via the NMDA receptor. PMID- 8369486 TI - Analgesic effect of morphine, clonidine and serotonin microinjected into the PTN of rats. AB - The study was aimed to delineate the neurotransmitter receptors involved in pretectal analgesic mechanisms by direct microinjection of neurotransmitter agonists and antagonists through chronically implanted cannulae in the pretectal nucleus of rats. Morphine, clonidine and serotonin, at doses of 2.5 and 5.0 micrograms microinjected into the pretectal nucleus, produced a significant and prolonged analgesia as measured by the tail-flick test. The analgesia produced by morphine, clonidine and serotonin is significantly attenuated by pretreatment of the animals with naloxone (1 micrograms), yohimbine (5 micrograms) and methysergide (5-10 micrograms) respectively. The results indicate the possible involvement of opioid, adrenergic and serotonergic mechanisms in pretectal analgesia. PMID- 8369487 TI - Association of the peptidase inhibitor RB 101 and a CCK-B antagonist strongly enhances antinociceptive responses. AB - The brain peptide cholecystokinin (CCK) has been shown to counteract the analgesic effects of morphine suggesting a physiological antagonism between opioid and CCK neural systems. This has been definitely demonstrated in this study by co-administration of the CCK-B selective antagonist L-365,260 with RB 101, a systemically active inhibitor of peptidases, which fully protects the endogenous opioids, the enkephalins, from their inactivation. The naloxone reversible analgesic effects induced by RB 101 in the mouse hot-plate and rat tail-flick tests were strongly increased by low doses of L-365,260. These results could have important clinical applications by reducing the efficient dose of RB 101, which has recently been shown to be practically devoid of morphine-like side effects. PMID- 8369488 TI - L-deprenyl increases GFAP immunoreactivity selectively in activated astrocytes in rat brain. AB - L-deprenyl is a selective inhibitor of monoamine oxidase (MAO) B, an enzyme predominantly localized in astrocytes. We have investigated the effect of treatment with L-deprenyl (0.25 mg kg-1 day-1) on glial fibrillary acidic protein (GFAP) immunoreactivity (IR) after lesioning the rat striatum with an injection cannula. No effect of drug treatment on GFAP IR was found in unlesioned striata. A significant increase (p < 0.01 vs saline treated rats) in GFAP IR was found in the tissue surrounding the lesion in striata of rats treated with L-deprenyl for 4 days after the lesion. When post-treated for 42 days, however, L-deprenyl no longer increased GFAP IR although reactive astrocytes were still present in the lesioned area. These results suggest that L-deprenyl can enhance the activation of astrocytes during a critical time-period following a striatal injury. PMID- 8369489 TI - TrkA NGF receptor expression by non-cholinergic thalamic neurons. AB - Expression of the trkA receptor for nerve growth factor was analyzed by mRNA in situ hybridization in the telencephalon and diencephalon in adult rats. Two densely packed populations expressing trkA mRNA were detected in the thalamus, in the paraventricular thalamic nucleus anterior and reuniens thalamic nucleus. These neurons did not express mRNA coding for choline acetyltransferase. In basal forebrain and striatum, trkA and choline acetyltransferase mRNAs showed identical patterns of expression, supporting the view that trkA expression is confined to cholinergic population in these areas. In contrast, cholinergic neurons of the medial habenula did not express trkA mRNA. Our findings suggest the existence of previously undiscovered populations of non-cholinergic, NGF responsive populations in the thalamis. PMID- 8369490 TI - Theta-like activity in hippocampal formation slices: cholinergic-GABAergic interaction. AB - Brain slice preparations obtained from the rat were used to study cholinergic GABAergic interaction in mechanisms responsible for production of theta-like activity in hippocampal slices maintained in vitro. Bicuculline, a GABA-A antagonist, applied at 25 microM facilitated the effect of low concentration carbachol (25 microM) in inducing theta-like oscillations. At 100 microM, bicuculline increased the amplitude of carbachol-induced theta-like slow waves. This carbachol-bicuculline induced field potential was antagonized by a muscarinic blocker, atropine sulphate, and a GABA-A agonist, muscimol. These results provide in vitro evidence for cholinergic-GABAergic interaction in the production of hippocampal theta-like slow waves. PMID- 8369491 TI - Trans-azetidine-2,4-dicarboxylic acid activates neuronal metabotropic receptors. AB - The expression of metabotropic glutamate receptors (mGluRs) in primary cultures of cerebellar granule neurones can be: (i) modulated by the degree of depolarization during the culture period, rendering neurones differently sensitive to agonist-stimulated inositol phosphate (IP) hydrolysis; (ii) down regulated by specific mGluR agonists. In this culture the new rigid glutamate analogue, (+/-)-trans-azetidine-2,4-dicarboxylic acid (t-ADA) and the known mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) stimulated IP formation in line with the depolarization-modified expression of mGluR1. However, the two compounds caused different patterns of mGluR down-regulation. The effects of t-ADA and 1S,3R-ACPD were also tested on transformed human embryonic kidney 293 cells transfected with mGluR1. Only 1S,3R-ACPD, but not t-ADA, stimulated IP hydrolysis, suggesting that t-ADA acts on a subtype of metabotropic receptors different from mGluR1. Hence, t-ADA might prove useful in differentiating the function of various mGluR subtypes. PMID- 8369492 TI - Effects of coencapsulated NGF and GM1 in rats with cortical lesions. AB - Nerve growth factor (NGF) and monosialoganglioside GM1 were microencapsulated in biodegradable co-polymer poly(L-lactide):co-glycolide and administered locally to rats with unilateral cortical devascularizing lesions. Microcapsules were placed directly onto the lesioned cortical surface and rats were sacrificed 30 days post operatively. Biochemical and quantitative immunocytochemical analyses revealed effective protection from degenerative changes of nucleus basalis magnocellularis (NBM) cholinergic neurones on the lesioned side as well as a significant increase in choline acetyltransferase activity in the frontoparietal cortex surrounding the lesion. Results of this study strongly suggest that the topical application of microcapsules of a biodegradable polymer containing a mixture of two neuroprotective factors is a viable alternative to the use of osmotic minipumps for delivery of these agents into the CNS. Indeed, this approach might find clinical applications. PMID- 8369493 TI - Purkinje cell responses in the anterior cerebellar vermis during Pavlovian fear conditioning in the rabbit. AB - Extracellular single-unit recordings of Purkinje cells in the anterior cerebellar vermis (ACV) of the rabbit found evidence of short-latency (20-30 ms) differential responses to discriminatively-conditioned auditory stimuli during Pavlovian fear conditioning procedures. These differential unit responses appeared to be a function of learning as differential ACV Purkinje cell responses were not observed in naive (untrained) animals. Some of these evoked neurophysiological responses were also correlated with the behavioral conditioned autonomic response. (CAR); a conditioned bradycardiac response. These electrophysiological data, coupled with previous lesion results, suggest that the ACV is part of an important neural circuit for Pavlovian conditioned bradycardia. PMID- 8369494 TI - Hypothalamic modulation of Purkinje cell activity in the anterior cerebellar vermis. AB - Intricate anatomical connections exist between the cerebellar vermis and the hypothalamus. This study examined the effects of electrical microstimulation of the hypothalamus on Purkinje cell activity in the anterior cerebellar vermis (ACV) in the awake rabbit. Single-pulse stimulation of the hypothalamus evoked robust, short-latency modifications of Purkinje cell discharge. Heterogeneous response profiles were observed with cells demonstrating patterns of either unimodal excitation, biphasic excitation/inhibition or complex triphasic responses. These results support the hypothesis that the hypothalamus and ACV are functionally interactive, and may promote further understanding of the role of the ACV in emotional behavior and autonomic responses. PMID- 8369495 TI - A new brain stem pathway for vocal control in the zebra finch song system. AB - Projections from the telecephalic vocal control nucleus robustus archistriatalis (RA) to the brain stem were studied with anterograde and retrograde tracers in adult male Zebra finches. A previously undescribed projection to the ventrolateral medulla that originates in a dorsal subregion of the RA was found, in addition to the known projections to the tracheosyringeal portion of the hypoglossal nucleus (nXIIts) and to the dorsomedial nucleus of the intercollicular complex (DM), a mesencephalic vocal area. The DM was also found to project to the same area of the lateral medulla, which in turn projects to the nXIIts. This area in the lateral medulla includes the nucleus ambiguus, and may be of a pathway that links the telencephalic vocal pathway with respiratory control areas. PMID- 8369496 TI - Stimulation of glycolytic key enzymes in cerebral cortex by insulin. AB - In adult male Wistar rats, a test was conducted to find whether or not insulin, administered intracerebroventricularly, would stimulate the activities of the glycolytic key enzymes hexokinase and phosphofructokinase in brain tissue as in non-neuronal tissue. The data clearly demonstrated an increase in these enzyme activities in cerebral cortex by approximately 20% after 80 mU insulin, whereas the increase in the hippocampus was just short of statistical significance. It is concluded that insulin controls glycolytic flux in the brain, and the suggestion that any perturbation in insulin signal transduction has severe impacts on brain glucose metabolism seems justified. PMID- 8369497 TI - Laboratory methods for diagnosing and monitoring HIV infection. AB - The authors provide a brief review of laboratory methods used to diagnose infection, monitor HIV disease progression, and monitor response to treatment in the HIV-infected person. Included are descriptions of the characteristics of the HIV virus, and the immune damage that results from HIV infection. The authors describe the antibody tests, tests of the virus, "surrogate markers" of disease progression, and immune parameters. Nurses' understanding of these tests will facilitate effective patient monitoring and education. PMID- 8369499 TI - Evaluation of community-based nurse case management activities for symptomatic HIV/AIDS clients. AB - The purpose of this study was to evaluate case management activities performed by nurse case managers in the California Pilot Care and Waiver Projects for HIV/AIDS patients. Nurse case managers, social workers, and site directors completed a 62 item survey. Significant differences appeared in ratings among the groups on five items. The nurse case managers responding to the survey indicated that a wide variety of nursing skills are used to provide case management services to persons living with AIDS and AIDS-related complex. This survey validates the interdisciplinary case management model in a community-based HIV population. PMID- 8369498 TI - Stage of illness, level of HIV symptoms, sense of coherence and psychological functioning in clients of community-based AIDS counseling centers. AB - The psychological functioning of HIV-infected individuals in community populations has taken on new meaning and urgency for healthcare policymakers responding to the special challenges of the AIDS epidemic. The authors' objective is to test several hypotheses that predict depression and anxiety in adults infected with HIV. Data were obtained from 156 HIV-infected adults (age > or = 18) who sought support, counseling, and maintenance services from one of three HIV care and referral centers in the Mid-South. The results of the study emphasize the relative importance of perceived physical symptoms over stage of illness for psychological functioning among adults with HIV. PMID- 8369500 TI - A call for help: collaborative nursing research. AB - Key issues related to HIV nursing research are the focus of this literature review. Results of two prior literature reviews are combined with the author's current review to serve as a basis for discussion. Findings indicate that further research is needed, particularly in the area of physiological responses to nursing care. Collaboration between clinicians and researchers is viewed as the most effective way to conduct HIV nursing research. Suggestions related to ways of facilitating collaborative research are discussed. PMID- 8369501 TI - Pain characteristics and their management in persons with AIDS. AB - Discussion of pain problems in persons with AIDS has been limited in medical and nursing literature, yet pain is a major source of suffering and concern for patients. Common pain characteristics are described in 100 persons with CDC defined AIDS, using the 1987 definition. The two most frequently cited types of pain for both drugs users and nondrug users with AIDS were abdominal pain and neuropathic pain. Drug users experienced pain due to esophagitis and headaches more frequently than nondrug users, while nondrug users experienced Kaposi's sarcoma-related pain more often. Treatment responses were individualized, with drug users requiring more frequent use of opiates. General treatment strategies are suggested with special emphasis on the unique needs of PWAs. PMID- 8369502 TI - Atovaquone. PMID- 8369503 TI - Addressing the concerns of HIV-infected individuals. PMID- 8369504 TI - Don't forget the invisibles. PMID- 8369505 TI - Building bridges. PMID- 8369506 TI - Drugs are not enough. Failure of short-course chemotherapy in a district in India. PMID- 8369507 TI - Imaging and lung disease: uses and interpretation. AB - Diagnostic imaging has undergone a profound revolution since the first computed tomography (CT) unit was conceived in 1971; CT is now an integral part of daily practice in thoracic radiology, and has reached a relative technological maturity. Magnetic Resonance Imaging (MRI) has been introduced more recently. Technical difficulties still exist and are related to cardiac and respiratory motion. The storage-phosphor-based computed radiography system provides several advantages, including compensation for variations in exposure, but is still under evaluation especially in bedside radiography. Nevertheless careful plain film analysis still remains an important examination, and should be done before special procedures are taken to answer specific questions. Routine chest radiography is still the most frequent method of imaging employed today. Radiographic studies can suggest airway pathology such as atelectasis, endobronchial neoplasia or bronchiectasis, but CT provides a unique strategy for the localization and characterization of bronchial and pulmonary parenchymal disease. The most important role of CT is to determine, localize and characterize patterns within the pulmonary parenchyma, and correctly identify bronchiectasis even when bronchography is equivocal. In lung cancer, imaging has an important role in accurate staging with regard to the correct selection of patients and evaluation of prognosis. CT is one of the major tests used for staging. The staging system now adopted worldwide is based upon AJCC and ATS classification, and has two major components: anatomic extent of the disease (TNM) and cell types. The role of MRI with regard to lung cancer is not precisely determined. MRI can play a complementary role in the staging of lung cancer in cases of superior sulcus tumour; pericardial involvement, tumoral extension in subcarinal region and invasion of the superior vena cava. The radiologic detection of the solitary nodule is a difficult charge for the radiologist; CT provides the precise localization of the nodule and is reliable for analysing radiologic features such as calcification, cavitation, and spiculated borders. The problem remains of the discovery of an incidental benign pulmonary nodule in the patient with an extrathoracic malignancy, and often necessitates percutaneous biopsy under CT guidance. The evaluation of diffuse lung disease lies on pattern recognition. Chest radiography is the initial tool for diagnosis, high resolution CT (HRCT) can provide routine visualization of structures of less than 500 mu. HRCT can be useful in formulating a differential diagnosis with recognition of pattern and distribution of the disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8369508 TI - The HIV epidemic and its effect on the tuberculosis situation in The Netherlands. AB - To determine the influence of the HIV (human immunodeficiency virus) epidemic on the tuberculosis situation in the Netherlands, we made a retrospective analysis of all reported tuberculosis cases from 1984 through 1990. We studied the course of the tuberculosis incidence in the Netherlands among the group at highest risk for HIV infection (Dutch males, 25-49 years of age, in Amsterdam). This was compared with the course among same-age Dutch males in areas with lower risk for HIV infection and among other-age Dutch males in Amsterdam. The tuberculosis incidence among Dutch males aged 25-49 years in Amsterdam increased from 16.1 in 1984 to 34.7 per 100,000 in 1990 (chi 2 for trend, P < 0.01). The incidences among Dutch males in other places of residence in this age group and among other age Dutch males in Amsterdam remained stable or decreased during the same period. As this increase could not be ascribed to tuberculosis among other risk groups, it appears to be related to the HIV epidemic among male homosexuals. Our results indicate that, even in a country where the prevalence of tuberculous infection is low, an increase of tuberculosis among certain subgroups can be observed as the result of the HIV epidemic. PMID- 8369509 TI - Bacteriology and drug susceptibility of tuberculosis at St Vincent's Hospital, Melbourne 1962-1991. AB - 39,000 specimens were examined for the growth of Mycobacterium tuberculosis over a 27-year period (1962-1989) at St Vincent's Hospital, Melbourne. The culture positive rate was 2.0% overall but was as high as 3.5% for tissue specimens and less than 1% for specimens of pleural fluid. There were 329 culture positive patients over a 29-year period (1962-1991) of whom 34 (10.5%) yielded an isolate resistant to at least one anti-tuberculosis drug and 19 (5.8%) were resistant to isoniazid. An overall increase in the rate of drug resistance together with important ethnic group differences were noted. PMID- 8369510 TI - Six years' experience with the discontinuation of BCG vaccination. 1. Risk of tuberculosis infection and disease. AB - BCG vaccination programmes were introduced into Czechoslovakia 40 years ago under a quite different epidemiological situation than that of today. Compulsory mass BCG vaccination of infants born in a selected area was discounted in 1986, except for those having a high risk of contracting tuberculosis or those whose parents expressly asked for it. The aim of this study was to ascertain the risk of tuberculosis infection and breakdown rate from infection to disease in 165,854 newborns following a period of 6 years. The average risk of infection in children aged 0-6 years was low (0.046%). No identifiable factors increasing the risk of infection were found. Primary tuberculosis was diagnosed in 31 children (7/100,000 persons/year); this corresponds to a 15.5% breakdown rate from infection to disease. The majority of patients were symptom-free with minimal disease and detected in the course of regular check-ups. These findings indicate that the change from mass BCG vaccination to selective vaccination of high risk newborns can be recommended. Nevertheless social and economic aspects which involve migration, living conditions and the attitudes of the population, as well as of medical staff, to vaccination should also be taken into consideration. PMID- 8369511 TI - Oral corticosteroids in patients with mild Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome (AIDS). AB - OBJECTIVE: To assess the effect of oral corticosteroids in patients with mild Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome (AIDS). DESIGN: Prospective, double blind, placebo controlled, randomized trial. METHODS: Included were AIDS patients having their first episode of P. carinii pneumonia, who had no other known active pulmonary pathology, who had no contraindications for corticosteroids and who had received no other anti-P. carinii medications for more than 48 h. Subjects received either prednisone, 60 mg/day for 7 days, followed by a progressive tapering over 14 days, or identical placebo. The present analysis pertains to patients with mild P. carinii pneumonia as defined by a baseline resting oxygen saturation greater than 90% and a decrease in oxygen saturation during exercise while breathing room air of not less than 5 percentage points. Early deterioration, the end-point of the trial, was defined as a 10% decrease from baseline oxygen saturation on day 3 or thereafter. RESULTS: At study termination, there were 12 subjects in the placebo group and 11 in the corticosteroid group. Baseline characteristics were not statistically different between the treatment groups. Early deterioration developed in 7 and 1 patients in the placebo and corticosteroid groups respectively (P = 0.027). In addition, by day 3, a number of parameters were less favorable in the placebo group relative to the corticosteroid group including median oxygen saturation (85% vs 97%; P = 0.003), lactic dehydrogenase (1514 vs 763; P = 0.013), median respiratory rate (30 vs 22; P = 0.003), median heart rate (100 vs 81; P = 0.002), and median temperature (39 vs 37; P = 0.024). Even though patients suffering early deterioration in the placebo group were switched to corticosteroids, significant differences between the groups remained at day 30 with regard to exercise tolerance. More than half of patients assigned to the corticosteroid group exercised for a median of 6.5 min on day 30 (P = 0.017). CONCLUSION: Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with mild AIDS-related P. carinii pneumonia as defined on the basis of pulse oximetry. PMID- 8369512 TI - Critical assessment of smear-positive pulmonary tuberculosis patients after chemotherapy under the district tuberculosis programme. AB - This is a status report of a retrospectively assembled cohort of 3357 smear positive patients initiated on anti-tuberculosis chemotherapy in the North Arcot district between April 1986 and March 1988. The patients were contacted once at their homes between November 1988 and June 1989 (6 and 36 months after start of treatment), and information on their status, including death, could be obtained from 76% of them. Regimens were selected by the patients. 2306 (69%) had accepted short course regimens (SCC) and 1051 (31%) had been started on standard chemotherapy (non-SCC), 43% and 35% in SCC and non-SCC respectively had completed 80% or more of their treatment. Overall mortality was 28%. Of those remaining, 31% had active disease and were excreting bacilli, among which 65% of the cultures were resistant to isoniazid and 12% to rifampicin. Combined resistance to isoniazid and rifampicin was seen in 4% and to isoniazid and streptomycin was seen in 19%. A significant finding was that even among those who had taken less than 50% of their treatment, 56% were bacteriologically negative. However, inadequate or irregular chemotherapy resulted in over four times the mortality and about twice the rate of smear positivity as compared with those taking adequate chemotherapy. No comparisons are made between patients on short-course and standard regimens as the patients selected their treatment and the groups are not comparable. PMID- 8369513 TI - The role of bacterial super infection in extensive pulmonary tuberculosis. Data from protected brush cultures in untreated patients from the University of South Alabama Medical Center, Mobile, Alabama, USA. AB - Pulmonary tuberculosis (TB) and bacterial pneumonia are both characterized by fever, cough, and purulent sputum production. Although TB alone can cause these symptoms, the possibility of a concomitant bacterial pneumonia has led some clinicians to treat these patients empirically with antibacterial agents. Neither the benefit of such empiric antibiotic therapy nor transtracheal aspirate cultures from patients with pulmonary TB have yielded consistent results. Consequently, we performed a prospective study to obtain lower airway secretions via a bronchoscopic protected specimen brush (PSB) technique for quantitative aerobic and anaerobic cultures from untreated patients with extensive pulmonary TB (defined as cavitary disease or involvement of > or = 3 segments). We obtained bronchoscopic samples from 3 untreated men aged 21, 61, and 60 years with extensive pulmonary TB. There was no significant bacterial growth (aerobic or anaerobic) from the specimens obtained. These results, therefore, do not support the hypothesis that bacterial pneumonia is a common concomitant of extensive pulmonary TB. PMID- 8369514 TI - Negative sputum smear results in HIV-positive patients with pulmonary tuberculosis in Lusaka, Zambia. AB - During recruitment to a prospective study of tuberculosis patients in Lusaka, Zambia, 109 had pulmonary disease proven by sputum culture for Mycobacterium tuberculosis, of whom 72 were HIV-1 antibody-positive and 37 were HIV-negative. Among these culture-proven cases, 43% of the HIV-positive patients had a negative sputum smear, compared with 24% of the HIV-negative cases. There was a strong trend towards lower grade or negative sputum smear in the HIV-positive group (P = 0.003). HIV-positive cases also had lower colony counts on culture and colonies took longer to appear. The findings imply that cases of HIV-associated pulmonary tuberculosis may frequently be missed and emphasise the need for new diagnostic methods. PMID- 8369515 TI - The use of monoclonal antibodies to identify mycobacteria grown in culture in Zimbabwe. AB - Monoclonal antibodies (Mabs) were used in an ELISA system to identify 462 mycobacterial isolates from clinical specimens in Zimbabwe. Cultures of mycobacteria were either sonicated or mechanically homogenised and used to coat the wells of microtitre plates. The mouse Mabs used reacted to lipoarabinomannan, an antigen common to all species of mycobacteria, to a 16 kDa protein specific to members of the Mycobacterium tuberculosis complex, to a glycolipid found in the cell wall of M. kansasii and to a glycolipid found in the cell wall of members of the M. avium-intracellulare complex. On the basis of serologic reactivity 443/462 (94%) isolates were identified as M. tuberculosis, 6/462 (1%) were identified as M. avium-intracellulare and 7/462 (2%) were identified as M. kansasii. The remaining 16 isolates gave negative reactions with each of the monoclonals, except that reactive with lipoarabinomannan. On the basis of biological tests on the 13 of the isolates that were available, 6 were identified as M. tuberculosis and 3 as M. bovis. In each of these the optical densities in the ELISA with at least one of the Mabs directed against the 16 kDa protein, was within 0.2 units of the cut off value. 4 isolates were not identifiable using biological tests in our laboratory. Each of the available isolates identified serologically as M. avium-intracellulare or M. kansasii gave biological reactions consistent with this identification. This study has shown Mab-ELISA to be a reliable means of rapidly identifying large numbers of mycobacterial isolates in a reference laboratory in Zimbabwe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369516 TI - Detection of antigens of Mycobacterium tuberculosis in patients of infertility by monoclonal antibody based sandwiched enzyme linked immunosorbent assay (ELISA). AB - A sandwich ELISA to detect specific protein antigens of Mycobacterium tuberculosis was developed by using polyclonal anti-BCG rabbit antibodies as the primary capture antibodies. The mycobacterial antigens were detected with horseradish peroxidase conjugated monoclonal antibodies (P 6) as secondary antibodies. The enzyme was detected by using 1,2 Phenylenediamine dihydrochloride (OPD) and Hydrogen peroxide as substrate. The antigen could be quantitated through linear regression analysis with lower detection limit of 1.25 micrograms/ml. 50 consecutive cases of infertility were examined by laparoscopy and tested for the presence of the antigen in the serum. Mycobacterial antigen could be detected in 9 of the 12 cases with definitive diagnosis of tuberculosis, 5 of the 23 where the diagnosis of tuberculosis was probable and in only 1 of 15 patients who had no laparoscopic abnormalities indicative of tuberculosis. PMID- 8369517 TI - Pancytopaenia associated with disseminated tuberculosis, reactive histiocytic haemophagocytic syndrome and tuberculous hypersplenism. AB - A 38-year-old black male is reported with a rare combination of disseminated tuberculosis together with a reactive histiocytic haemophagocytic syndrome and tuberculosis hypersplenism. Tuberculosis and histiocytic haemophagocytosis were diagnosed on bone marrow examination. The pancytopaenia and splenomegaly which were present on admission did not resolve despite adequate anti-tuberculosis chemotherapy. Prior to splenectomy the patient continued to have a marked thrombocytopenia which resulted in recurrent bouts of epistaxis; splenectomy together with tuberculostatic therapy was curative for the condition. The patient remains well with normal blood counts 1 year later. PMID- 8369518 TI - Disseminated skeletal tuberculosis with skull involvement. AB - We report a patient with widespread osteolytic lesions, including extensive involvement of the skull, due to Mycobacterium tuberculosis. Response to treatment with antituberculosis drugs was slow with appearance of new lesions while on therapy despite a sensitive organism. Excision of diseased skull bone was eventually done, after which no new lesions appeared in the ensuing 14 months. PMID- 8369519 TI - Antituberculosis drug-induced hepatitis and HBsAg carriers. PMID- 8369520 TI - Larger axillary metastases in obese women and smokers with breast cancer--an influence by host factors on early tumor behavior. AB - To better define the influence by host factors on very early breast cancer behavior, we retrospectively analyzed nodal status, diameter of the largest axillary metastasis (M), diameter of the primary tumor (P), the M/P ratio, tumor estrogen receptor status, age, obesity, and smoking habits in 176 women with node positive breast cancer. Both M/P ratios and M were larger in the 72 obese women and in the 40 nonobese smokers than in the 64 nonobese nonsmokers after control for other factors. Step-wise regression analysis demonstrated independent associations between M/P ratios and obesity (p = 0.0002), larger primary tumors (p < 0.0001), more positive nodes (p < 0.0001), and smoking (p = 0.0268), as well as between M and obesity (p = 0.0201), larger primary tumors (p = 0.0093), and more positive nodes (p = 0.0001). Among the 104 nonobese women, smoking was associated both with larger M (p = 0.0257) and larger M/P (p = 0.0055). Our observations suggest more rapid growth by metastases in obese women and smokers with breast cancer, as well as earlier metastasis from their primary tumors. PMID- 8369521 TI - Epidermal growth factor receptor in breast cancer: correlation of quantitative immunocytochemical assays to prognostic factors. AB - Immunocytochemical assays for EGFR were performed on frozen sections from breast carcinomas (n = 209). Results were evaluated by computer assisted image analysis to accurately define the percentage of immunostained surface and the mean optical densities. Thirty seven percent (n = 77/209) of the tumors were EGFR positive, but about one third of them were faintly reactive (35%). No significant relationship was observed between EGFR tumor content and patient age, tumor size, histological type, histoprognostic grade, or axillary lymph node status. A negative correlation was observed with the results of estrogen receptor immunocytochemical assays and a positive correlation with immunodetectable cathepsin D and Ki 67 antigen evaluated according the same method. No correlation was found with HER-2/neu protein, aneuploidy, nucleolar organizor region distribution, and nuclear morphometry, also assessed by image analysis. These results suggest that immunocytochemical assays assessed on frozen sections and evaluated by image analysis are suitable for current and standardized evaluation of EGFR which has been previously documented as a prognostic indicator in breast carcinomas. PMID- 8369522 TI - The pattern of diagnosis of a second primary tumor in the breast. AB - One hundred and sixty-seven patients with metachronous bilateral breast cancer were diagnosed at the Northern Israel Oncology Center during the years 1950-1989. The group at high risk to develop a second breast tumor included Jewish women born in Europe whose first tumor was diagnosed when the patient was under the age of 55. The mean time interval between tumors was 88 months. Seventy percent of the patients were diagnosed within nine years of the diagnosis of the first tumor. The characteristics of the 27% of patients with single breast cancers who did not comply with follow-up recommendations were compared to those who did comply. Patients who were under follow-up had smaller tumor and less lymph node involvement. Nevertheless, their survival rate did not differ from those who did not keep their follow-up appointments. This was ascribed to the fact that follow up procedures for many years used mainly clinical examination and this was not enough to decrease mortality. The diagnosis of non-palpable breast cancer by routine yearly mammography has proved to reduce mortality in patients over the age of 50 with single breast cancers. Therefore, yearly mammography of the contralateral breast in patients with single breast tumors must be done in order to increase the cure rate of contralateral breast cancer. Less patient delay in diagnosis was found before the diagnosis of the second tumor than in patients with a single tumor. PMID- 8369523 TI - Medroxyprogesterone acetate inhibits the proliferation of estrogen- and progesterone-receptor negative MFM-223 human mammary cancer cells via the androgen receptor. AB - This study demonstrates for the first time, that medroxyprogesterone acetate (MPA) inhibits the proliferation of the estrogen and progesterone receptor negative mammary cancer cell line MFM-223 via the androgen receptor. MPA is a progestin, which is used in the hormonal treatment of disseminated breast cancer. It binds to the progesterone, androgen, and glucocorticoid receptor and may exert its antiproliferative effects via different receptors. MFM-223 human mammary cancer cells contain a very high level of androgen receptors (160 fmol/mg protein) and low levels of estrogen, progesterone, and glucocorticoid receptors (< 20 fmol/mg protein). This cell line provides therefore a good model system to analyze the possible role of the androgen receptor in the action of MPA avoiding interference with other steroid hormone receptors. Effective inhibition of proliferation is achieved by 10 nM MPA or 1 nM of the androgen dihydrotestosterone, corresponding well to the binding affinities of both compounds (3.6 and 0.18 nM, respectively). The involvement of the androgen receptor was confirmed by competition experiments with antiandrogens. Furthermore, MFM-DHT cells, which are an androgen resistant subline of MFM-223 cells, are also resistant to MPA. This data supports the involvement of the androgen receptor in the action of MPA and additionally rules out direct hormone independent cytotoxic effects of MPA. PMID- 8369524 TI - The influence of a novel cyclopropyl antiestrogen (compound 7a) on human breast cancer cells in culture. AB - Compound 7a ([Z]-1,1,-dichloro-2,3-diphenyl-2-(4-(2- dimethylamino)ethoxy)phenyl) cyclopropane, dihydrogen citrate salt) is a novel cyclopropyl antiestrogen which was shown to be an estrogen antagonist without estrogen agonist activity. The antiproliferative activity of 7a was examined on estrogen receptor (ER) positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells and A-549 human lung cancer cells. Compound 7a inhibited the growth of MCF-7 cells in a dose-related manner over a concentration range of 10(-9) to 10(-5) M, but did not alter the growth of MDA-MB-231 or A-549 cells. The antiproliferative activity of 7a (10(-7) M) on MCF-7 cells was reversed by co-administration of estradiol (10(-8) M). An ER-dependent mechanism of action is also supported by the specific ER binding of 7a in MCF-7 cells observed in this study. A study of cell surface morphology using scanning electron microscopy (SEM) revealed that compound 7a at 10(-6) M reduced the length and density of microvilli (MV) on MCF-7 cells, which was reversed by co-administration of estradiol (10(-8) M). Compound 7a did not alter the cell surface morphology of ER-negative MDA-MB-231 cells. In conclusion, 7a inhibited the growth of ER-positive MCF-7 cells in an estradiol-reversible manner, and had no effect on ER-negative MDA-MB-231 cells or A-549 lung cancer cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369525 TI - The prognostic effect of histological tumor grade in node-negative breast cancer patients. AB - The prognostic effect of histological tumor grade was evaluated in 1036 patients with early breast cancer (pT1 pN0 M0) entered into a trial comparing mastectomy and breast preserving treatment. All analyses were adjusted for the factors treatment, patients' age, and tumor size. Tumor grade was defined according to Bloom and Richardson based on the sum of scores assigned to each of three histological features: 1) degree of differentiation, 2) pleomorphism, and 3) mitotic index. The relative importance of these factors with regard to disease free survival was evaluated. In univariate as well as in multivariate analyses the pleomorphism was the only factor showing a significant effect (univariate: p = 0.0024, multivariate: p = 0.015). It was investigated how the factors should be combined to define a histological grading score which yields the best possible classification of the patients with respect to prognosis. A new grading system was defined splitting the patients into three groups: 1) pleomorphism 1; 2) pleomorphism 2 or pleomorphism 3 and mitotic index 1; 3) pleomorphism 3 and mitotic index 2 or 3. This yields a good classification of the patients with respect to prognosis (p = 0.0004). The prognostic effect of this score was compared with the effects of the grading systems proposed in the literature. According to Bloom and Richardson and in the modified version by Schauer and Weiss, grading is based on the sum of scores of the various histological factors. Therefore, the strong effect of the pleomorphism was diluted in these grading definitions (Bloom and Richardson: p = 0.03, Schauer and Weiss: p = 0.028). The grading system proposed by Le Doussal et al. consists only of the scores of pleomorphism and mitotic index (p = 0.014). In summary, the factor pleomorphism showed a stronger effect on disease-free survival by itself than the grading systems proposed in the literature. PMID- 8369526 TI - Markers of prognosis in breast cancer--the relationship between binding of the lectin HPA and histological grade, SPF, and ploidy. AB - Abnormal cellular glycosylation as demonstrated by the binding of a lectin from Helix pomatia (HPA) to paraffin-embedded sections has been shown in several studies to be associated with aggressive biological behaviour and poor long-term patient prognosis in breast cancer. This study aims to address the possibility that expression of the HPA binding ligand may be of prognostic significance through an association with increased cellular proliferation (as measured by S phase fraction and histological grade), anaplasia (reflected in histological grade), or ploidy (DNA index). In a 24 year retrospective study, paraffin embedded sections of 366 primary breast cancers were stained for binding of HPA. All tumours were assessed for histological grade. Flow cytometry was performed on all cases for which sufficient tumour tissue was available (358/366 cases) and S phase fraction (SPF) and ploidy calculated. Data regarding patient age at diagnosis, nodal status, and tumour size were also recorded. Life table analyses revealed survival advantage for HPA 'non stainers' in comparison to 'stainers' (p < 0.001); for patients with tumours of low grade vs. high grade (p < 0.001); and for those with tumours of low SPF vs. high SPF (p < 0.001). No survival advantage was shown for those with diploid vs. aneuploid tumours (p = 0.17). No association was apparent between HPA binding and grade, SPF, or ploidy (Chi squared values not significant). This was confirmed by multivariate analysis in which nodal status, tumour size, and SPF were independently predictive of survival. There was no confounding effect of grade, SPF, or ploidy upon the correlation between survival and HPA binding. HPA was, however, not independently predictive owing to its strong association with nodal status. The results of this study suggest that the prognostic significance of altered glycosylation, as detected by HPA binding, is unlikely to be through an association with proliferative rate, degree of anaplasia, or cellular ploidy, but may rather be through a direct association with the presence of nodal metastases. PMID- 8369528 TI - Long-term follow up of breast cancer patients treated for hypercalcaemia with aminohydroxypropylidene bisphosphate (APD). AB - No systematic data are available about the long-term follow up of breast cancer patients treated with amino-hydroxypropylidene bisphosphate (APD) for hypercalcaemia and about the results of APD treatment of recurrent hypercalcaemia in these patients. Treatment with intravenous APD (10-15 mg daily until normalization of the serum calcium level) normalized serum calcium in 29 of 31 patients with hypercalcaemia due to advanced breast cancer. Survival in these 29 patients varied between 8 and 693 days (median 140 days) and 7 patients achieved a partial remission or stabilisation of disease during subsequent anti-tumor therapy. In 16 of the 29 patients in whom APD treatment was initially successful, hypercalcaemia recurred after a median period of 65 days. Eleven of these patients received a second course of APD, which was equally successful as the first in terms of percentage of patients with normalization of serum calcium, total dose of APD needed, and duration to normalization of serum calcium. Recurrent hypercalcaemia occurred significantly faster after the second successful APD course (median 17 days) than after the first (median 65 days). When only patients with progressive disease were taken into account, recurrence of hypercalcaemia usually occurred early, both after a first (median 23 days) and after a second successful APD course (median 17 days). Normalization of serum calcium occurred in 4 of 6 patients receiving a third APD course, in all 3 patients receiving a fourth, and in 1 of 2 patients receiving a fifth course.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369529 TI - [HIV testing with the informed consent]. PMID- 8369527 TI - The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts. AB - An immunoconjugate composed of natural interferon alpha (nIFN alpha) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN alpha/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN alpha/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN alpha on the injected tumors. Further enhancement was obtained when nIFN gamma or nIFN gamma together with Mc5 (at a dose 10 times larger than that present in nIFN alpha/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of 125I-nIFN alpha/Mc5 by the tumors was greater and its elimination slower than for 125I-nIFN alpha alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alpha alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy. PMID- 8369530 TI - [Prevalence of anti C100-3 and HBsAg in blood donors--comparative study of total collected blood units, total collection adjusted to exclude repeat blood donations, and in first time blood donors]. AB - Prevalence of anti C100-3 and HBsAg in donor blood collected at the Hiroshima Red Cross Blood Center during the period of Aug., 1990 to July, 1991 was studied in three groups--total received blood units (187,532 units) without any adjustment, blood units after adjustment by excluding repeat donations of blood units by the same donors (142,160 units), and blood units of first time donors (28,596 units). The results of the study is summarized as follows. 1) There was no significant difference in the prevalence of anti C100-3 between the group comprising the total collected units, and the group after the adjustment. This result suggests that repeat donors do not necessarily belong to any fixed age group. 2) The prevalence of HBsAg is significantly higher in the first time donor group than in the other two groups. In both the total blood units group and the group after the adjustment, prevalence of HBsAg among older age groups was as low as that of younger age groups. This is presumably because of the introduction of selective exclusion of HBsAg positive subjects from donors since 1980. When data from blood donors are used for the epidemiological studies of viral infection among healthy subjects, it is important to know the characteristics of such donor subjects and whether or not they are pre-screened for the viral markers in question. PMID- 8369531 TI - [Efficacy of influenza vaccination and its relationship to daily absentee rate]. AB - To determine the efficacy of influenza vaccination and it's relationship to "daily physical condition", an investigation was carried out in two elementary schools and one junior high school. Since children who had many absences during the first and second trimesters, tend to have many absentee days in the third trimester and during the last year, also, absentee rate during the first and second trimesters was considered to be an indicator of "daily physical condition". Vaccinated children tended to have lower absentee rates than nonvaccinated children during the first and second trimesters. This indicates that there is a definite difference between vaccinated and nonvaccinated children in terms of "daily physical condition". Children who had many absences during the first and second trimesters, also tended to have many absentee days during the influenza season, introducing a confounding factor, "daily physical condition", when comparisons are made in the absentee rate between vaccinated and nonvaccinated children during the influenza season. Careful analysis of these data, taking into account their "daily physical condition", showed that vaccinated children tended to have lower absentee rates than the nonvaccinated during the influenza season. However there was no definite difference between vaccinated and nonvaccinated children in length of absentee days during the influenza season. PMID- 8369532 TI - [Relationships among blood pressure, 24-hour urinary electrolyte excretion, and alcohol consumption]. AB - Relationships among blood pressure (BP), 24-hour urinary electrolyte excretion, and alcohol consumption were studied in 104 men and 229 women aged over 30 years living in a rural village in Kyoto, Japan. Twenty four hour urine was collected for two consecutive days to measure Na, K, Ca, Mg, and creatinine (Cr). In men, age, obesity index (OI), Ca/Mg ratio, and (Na.Ca)/(K.Mg) ratio were significantly related to BP. In women, diastolic blood pressure adjusted for age and OI, but not systolic blood pressure correlated with Na/K. Among male daily drinkers, the Ca/Mg ratio and (Na.Ca)/(K.Mg) ratio were significantly increased and K/Cr was significantly decreased. Results of path analysis confirmed the relation of BP to alcohol consumption and suggests that urinary electrolytes change in hypertensive drinkers. PMID- 8369533 TI - [Visual acuity testing of three- and four-year old nursery school and kindergarten children]. AB - Visual acuity testing was conducted on 1,531 children in nursery schools and kindergartens in Chita district, for the purpose of determining the rate of successfully performing the test, as well as the visual acuity of those shown to be normal by various ophthalmologic examinations. The rate of successful performance of the visual acuity test increased monthly with increasing age, with maximum changes seen at 4-5 months after the third birthday. The rate of successful performance of the test at the third birthday was 73%, progressively increasing up to 95% in the successive 6 months. The rate at the fourth birthday became almost 100%. Average of visual acuity of 3.0-year old children was 0.55, and for 3.5-year olds was 0.82. The average visual acuity reached 0.88 at 4.0 years of age, and at 4.5 years of age became 0.97. In view of the results obtained, it is concluded that children who could not successfully perform a visual acuity test at 3.0-years of age should be tested again at 3.5-years of age. Preferably the vision screening should be performed during the period between 3.5- and 4.0-years of age, for reliability and efficiency. Accordingly, the screening standards should also be changed with consideration given to visual development of children of this age. PMID- 8369534 TI - [Relationship of proportion of DCO cases in cancer registration to gastric cancer screening participation rate and proportion of all referred inpatients diagnosed with neoplasm]. AB - Of all cancer cases registered the proportion where identification is solely from death certificates, (DCO-Death Certificate Only), is one of the important indices for assessing the accuracy of the cancer registration system. Regional differences exist in the proportion comprised of DCO cases. These differences were analyzed in terms of the regional differences that also exist in gastric cancer screening participation rates, proportion of all referred inpatients with diagnoses of neoplasm by place of residence, and proportion of all referred inpatients with diagnoses of neoplasm by place of treatment. Up to 65% of the regional differences in DCO proportion can be explained by these three factors. PMID- 8369535 TI - [Repellent effect of wood odors on mites]. AB - Since mites are known to react to odor, the repellent effect of wood odors on mites was measured with a simple indicative method of mite evasion behavior. This experiment confirmed that the odors of three types of trees including Hinoki (Chamaecyparis obtusa), Pine (Pinusdensiflora) and Cedar (Cryptomeria japonica), had repellent effects on Tyrophagus putrescentiae, Dermatophagoides farinae and D. pteronyssinus, mite specics which are comminly found in houses. The effects of Lauan (Shorea spp.) and Spruce (Picea sitchensis) were less than those of Hinoki, Pine and Cedar in stimulating evasion response. In comparing the evasion behaviors of three species of mites to wood odors, the responses of D. farinae and D. pteronyssinus seemed to be stronger than those of T. putrescentiae. Very little differences in responses between males and females of these mites were seen. PMID- 8369536 TI - [Assessment of malocclusion among Japanese junior high school pupils of Matsuo, Iwate Prefecture using dental aesthetic index (DAI)]. PMID- 8369537 TI - [Evaluation of personal computer program for measuring energy expenditure in a day among college students]. PMID- 8369538 TI - [Method to confirm the efficacy of health education for hypertensive patients]. PMID- 8369539 TI - Comparison of sound quality and clarity with asymmetrical peak clipping and output limiting compression. AB - This study compared the preferences of 12 subjects with mild-to-moderate hearing losses for a linear circuit when the type of output limitation could be changed between asymmetrical peak clipping and output limiting compression. Through a paired-comparison paradigm, subjects rated the sound quality and clarity of speech in quiet, speech in noise, and music when the output levels were well below saturation and when slight saturation and high saturation occurred. A significant preference was found for the output limiting compression for each of the three stimuli for both sound quality and clarity. The preference became stronger with increases in saturation. The results suggest that if linear hearing aids are being used, the output should be limited with compression rather than peak clipping. PMID- 8369540 TI - Rate, frequency, and intensity effects on early auditory evoked potentials and binaural interaction component in humans. AB - The binaural interaction component (BIC) of the auditory brainstem response (ABR) and BIC of the frequency-following response (FFR) to tonal stimuli were studied in normal-hearing adults. The ABR and BIC latencies from all subjects were consistently shorter to the click-like sound than to the 2.0 kHz tone burst. Increasing stimulus presentation rate produced longer latencies and diminished amplitudes of ABR and BIC waveforms. The consequences of rate changes were independent of sound level. The FFR and BIC latencies to low-frequency tone bursts (0.5 and 1.0 kHz) were minimally affected by rate, but their amplitudes were modified. The results are consistent with and reflective of the functional characteristics of lower brainstem auditory neurons. The results provide evidence that the BIC to tones is differentially sensitive to the rate, frequency, and intensity of sounds other than clicks. PMID- 8369541 TI - Speech-evoked cortical potentials in children. AB - Event-related potentials (ERPs) were obtained to synthesized speech stimuli in 16 school-aged children (7-11 years) and compared to responses in 10 adults. P1, N1, and P2 event-related potentials were elicited by the phoneme /ga/. The mismatch negativity (MMN) was elicited by variants of /da/ and /ga/, which differ in the onset frequency of the second and third formant transitions. In general, the well defined N1/P2 complex characteristic of the adult response, was not found in children. Waves P1 and N1 had longer peak latencies in children than in adults. Wave P2 amplitude was smaller in children than in adults. In contrast to the often poorly delineated earlier cortical potentials, the MMN was well defined in children. Significant MMNs were obtained in all subjects tested. MMN magnitude (peak amplitude and area) was significantly larger in the children. No significant differences were found in peak latency and duration of the MMN in children compared to the adult response. Another negative wave occurring at 400 msec was also observed in response to the deviant stimuli. This negative wave occurred at a similar latency in adults and children and was significantly larger and more robust in children. Results support the view that development of ERPs does not involve a hierarchical process with respect to latency. That is, earlier occurring waves do not necessarily mature before later occurring waves. The latencies of P1, N1, and P2 and overall morphology of these waves may provide a measure of maturation of central pathways. The early development of the MMN, its apparent robustness in school-aged children, and its reflection of the processing of acoustic differences in speech stimuli suggest its possible use in the assessment of central auditory function. PMID- 8369542 TI - Some factors affecting assessment of hearing handicap in the elderly. AB - In 42 elderly hearing-impaired persons we compared the patient's self-assessment of hearing handicap with the assessment made by the patient's significant other. In general, patients tended to rate themselves as less handicapped than did their significant others. The difference was not affected by degree of loss but was affected by slope of loss and by the presence of central auditory processing deficit. Results support the value of the handicap assessment by the significant other in understanding the communication problems of the elderly patient. PMID- 8369543 TI - Effects of audiometric threshold step size on proposed ANSI S12.13 outcomes for characterizing hearing conservation program effectiveness. AB - Audiometric records of 213 employees with low noise exposure were selected from the public domain data base underpinning Draft American National Standards Institute (ANSI) S12.13-1991 Standard Evaluating the Effectiveness of Hearing Conservation Programs. Records were selected from an ANSI S12.13 "control" group demonstrating raw audiometric thresholds in 1-dB steps, presumably resulting from self-recording audiometry. Raw audiometric data were rounded to the nearest 5-dB step, and ANSI S12.13 analysis protocols were applied to both raw and rounded data sets. The magnitude of all proposed ANSI test statistics increased with audiometric step size. Percent worse sequential and percent better or worse sequential protocols were markedly more sensitive to threshold step size than standard deviation of difference thresholds. The direction and magnitude of change in these outcomes supports the assumption that criterion ranges in the draft standard hold artifactual bias against hearing conservation programs (HCPs) collecting audiometric data in 5-dB steps. PMID- 8369544 TI - Detecting and remediating external meatal collapse during audiologic assessment. AB - We present a case study in which the jaw/mouth-open procedure during air conduction testing is employed to both detect and remediate external auditory meatal collapse. A prospective investigation was also conducted to compare the efficacy of the proposed jaw/mouth-open procedure with that of the traditional insert receivers in remediating meatal collapse during audiologic assessment. Meatal collapse was present in 6 of the 136 subjects evaluated. In these 6 subjects, the air-conduction thresholds under supra-aural headphones in the jaw/mouth-open condition were similar to those under insert receivers. We discuss the implications of this finding in clinical settings where insert receivers are not available. PMID- 8369545 TI - Prolonged I-III interwave interval in cerebellar astrocytoma. AB - We are reporting the case of a 41-year-old female diagnosed with a cerebellar astrocytoma. The tumor was detected after the patient was referred for MRI scan because of an abnormal ABR. The ABR was unusual as the I-V interwave intervals (IWIs) were within normal limits bilaterally, but the I-III IWI was prolonged by .40 msec on the left ear in comparison to the right ear. This case report illustrates the importance of the I-III IWI in the detection of retrocochlear pathology and the nonsequential generation of the components of the ABR. PMID- 8369546 TI - Aided masked thresholds: case of deception. AB - A case of contaminated functional gain measures from internal hearing aid noise is presented and clinical implications addressed. The contaminated functional gain measures underestimated real ear insertion gain. Recognition of this source of functional gain measurement error is essential for accurate hearing aid fitting. PMID- 8369547 TI - Confounding binaural interactions. PMID- 8369549 TI - The role of extracellular calcium in generating and in phase-shifting the Bulla ocular circadian rhythm. AB - Since extracellular calcium is known to be involved in the entrainment of the circadian pacemaker in the retina of Bulla gouldiana, we have assessed the requirement for extracellular calcium in the generation of the circadian rhythm. To enable us to assay the state of the pacemaker during low-calcium treatment, which often obscures rhythmicity, long-duration pulses of low-calcium artificial seawater (no added calcium, 10 mM EGTA, calculated calcium concentration = 4.5 x 10(-10) M) were applied, and the phase of the subsequent rhythm was measured. Pulse treatments started at zeitgeber time (ZT) 6, and durations ranged from 4 to 72 hr. Although no phase shifts followed pulses ending before the next projected dawn (ZT 24), phase delays of up to 4 hr followed pulses ending after projected dawn, and delays of up to 8 hr followed pulses spanning two dawns. Some activity records exhibited unequivocal circadian rhythmicity during the long low-calcium treatments, with phases and periods similar to untreated control eye records; this finding suggests that the phase delays observed following long low-calcium pulses are attributable to the pulsatile nature of the treatment. These data suggest that extracellular calcium is not an essential requirement for the pacemaker in generating the circadian rhythm. PMID- 8369548 TI - Circadian rhythm in the visual system of the lizard Anolis carolinensis. AB - The electroretinogram (ERG) was recorded from free-moving Anolis lizards once per hour for 5 days. As in our previous work, the b-wave, but not the a-wave, showed a reliable circadian rhythm (CR) in amplitude, with an acrophase near projected noon. Both the a- and b-waves showed a CR in peak time (implicit time, or IT), with the a-wave IT being longest near midnight, and the b-wave IT at midday. Acrophases were shifted when animals were housed on a phase-shifted light-dark cycle. The ERG CR was unaffected by removal of the parietal organ, but it was virtually abolished by removal of the pineal gland, thus suggesting that pineal output (probably melatonin) modulates retinal responses. In addition to the ERG, the tectal light-evoked potential exhibited a CR--a finding compatible with a circadian variation in retinal output. Lastly, the amplitude of the ERG component waveforms showed a seasonal variation, but the ERG CR was constant across the year. PMID- 8369550 TI - Circannual rhythms in starlings: response of castrated birds to 12-hr days depends on photoperiodic history. AB - The annual cycle of reproductive function in starlings (Sturnus vulgaris) is driven by seasonal changes in daylength and consists of a 6-month period of photosensitivity, culminating in maximal gonadal development, followed by a 6 month period of photorefractoriness. If male starlings are held under a constant photoperiod of 12 hr of light per day (LD 12:12), some individuals show circannual rhythms of testicular size. Do these rhythms consist of alternating periods of photosensitivity and photorefractoriness, and does the response depend on whether daylength is increased or decreased to 12 hr? Castrated starlings were transferred from natural short days in January (LD 9.5:14.5) to LD 12:12. Plasma LH decreased and then remained low for 2.5 years. Most birds molted, some twice. Other castrated birds were transferred from long days in August (LD 16:8) to LD 12:12. Plasma LH increased and then remained high for 15 months. None of these birds molted. Young starlings were exposed to LD 12:12 throughout incubation and thereafter. Plasma LH remained low until birds were 13 months old. All of these birds molted. These results demonstrate, first, that castrated starlings show no evidence of alternating periods of photosensitivity and photorefractoriness under LD 12:12; and second, that LD 12:12 can be perceived as a long day or a short day depending on photoperiodic history, and that young birds with no experience of any other daylength perceive LD 12:12 as a long day. PMID- 8369552 TI - Animal issues statement of the society for research on biological rhythms. PMID- 8369551 TI - Phase control of ultradian feeding rhythms in the common vole (Microtus arvalis): the roles of light and the circadian system. AB - In their ultradian (2- to 3-hr) feeding rhythm, common voles show intraindividual synchrony from day to day, as well as interindividual synchrony between members of the population, even at remote distances. This study addresses the question of how resetting of the ultradian rhythm, a prerequisite for such synchronization, is achieved. Common voles were subjected to short light-dark cycles (1 hr darkness with light varying between 0.7 and 2.5 hr); to T cycles (long light-dark cycles in the circadian range--16 hr darkness and 3-13 hr light); to light pulses (15 min) during different circadian and ultradian phases; and to addition of D2O to the drinking water (25%). Short light-dark cycles and D2O were also applied to voles without circadian rhythmicity, after lesions of the suprachiasmatic nuclei. In these experiments, four hypotheses on synchronization of ultradian rhythmicity were tested: (I) synchronization by a direct response to light; (II) synchronization via the circadian system with multiple triggers, here called "cogs," each controlling a single ultradian feeding bout; and (III and IV) synchronization via the circadian system with a single "cog," which resets an ultradian oscillator and either (III) originates directly from the circadian pacemaker, or (IV) is mediated via the overt circadian activity rhythm. Short light-dark cycles failed to entrain ultradian rhythms, either in circadian rhythmic or in non-circadian-rhythmic voles; light pulses did not cause phase shifts; and in extreme T cycles no stable phase relationship with light could be demonstrated. Thus, Hypothesis I was rejected. Changes in the circadian period (tau) were generated as aftereffects of light pulses, by entrainment in various T cycles, and by the addition of D2O to the drinking water. These changes in tau did not lead to parallel, let alone proportional, changes in the ultradian period. This excluded Hypothesis II. Both in T-cycle experiments and in the D2O experiments with circadian-rhythmic voles, the phase of ultradian feeding bouts was locked to the end of circadian activity rather than to the most prominent marker of the pacemaker, the onset of circadian activity. This was not expected under Hypothesis III, but was consistent with entrainment via activity (Hypothesis IV). On the basis of these experiments, we conclude that the most likely mechanism of ultradian entrainment is that of a light-insensitive ultradian oscillator, reset every dawn by the termination of the activity phase controlled by the circadian pacemaker, which is itself entrained by the light dark cycle. Neither in circadian-rhythmic nor in non-circadian-rhythmic voles was the period of the feeding rhythm lengthened by administration of D2O. This insensitivity to deuterium is exceptional among biological rhythms. PMID- 8369553 TI - The application of random amplified polymorphic DNA for sandfly species identification. AB - We have applied the recently developed Random Amplified Polymorphic DNA (RAPD) method to produce species-specific, DNA profiles for two sympatric, Venezuelan sandfly species, thought to be the vectors responsible for recent outbreaks of cutaneous and mucocutaneous leishmaniasis in the Andean State of Tachira. Moreover, within the profile, it was possible to identify a diagnostic DNA band for Lu. youngi of 0.32 kb. Results showed that the size of this diagnostic DNA band remained constant and did not vary with sex or geographical distribution. PMID- 8369554 TI - Analysis of mosquito bloodmeals by DNA profiling. AB - Human specific genetic markers have been used to profile the human DNA found within a mosquito bloodmeal. In this technique, variable numbers of tandem repeat (VNTR) sequences are employed to prime amplification of human DNA in the polymerase chain reaction (PCR) and the radiolabelled products are analysed by high resolution denaturing gel electrophoresis. Matching of DNA profiles allows identification of the individual human host. Bloodmeals of 125 female Anopheles gambiae Giles mosquitoes, caught dead or alive in verandah-trap huts wherein two people had slept overnight protected by intact insecticide-impregnated bednets, were analysed: thirty-five out of thirty-nine profiles generated were identical to those of the sleepers under the nets. Thus the blood-fed mosquitoes found after impregnated nets have been used cannot, in most cases, be explained away by entry of already fed mosquitoes into the huts. PMID- 8369555 TI - Host feeding preference of Phlebotomus guggisbergi, a vector of Leishmania tropica in Kenya. AB - Recently the sandfly Phlebotomus guggisbergi was found to be a vector of Leishmania tropica causing cutaneous leishmaniasis in the Laikipia focus, Kenya, but extensive searches have shed no light on the identity of the rural reservoir host(s). In order to discover more about the biology of the vector, a host feeding preference study was conducted on wild sandflies in their natural cave environment over a 6-month period. Solid state Army miniature (SSAM) traps, without light bulb, were suspended over cages with potential hosts or an empty cage control. The animals tested included sheep, goat, dog, cat, hamster, rabbit, giant rat (Cricetomys gambianus), crested rat (Lophiomys imhausi) and rock hyrax (Procavia capensis), all of which (except hamsters) are normally found in the vicinity of the study site. Sandfly collections from traps baited with goat, sheep, cat, dog, rabbit, or wild rodent species were significantly higher than the control, whereas trap collections with hamster and rock hyrax were not significantly different from the control. Numbers of sandflies collected from the goat, sheep and cat were significantly greater than from the rabbit and rodents. The sex ratio also varied between collections: larger animals attracted a higher proportion of female P. guggisbergi than did the smaller animals (P > 0.05). Therefore greater emphasis should be placed on surveying larger animals to assess their status as reservoir hosts for L. tropica in Kenya. PMID- 8369556 TI - Semiochemical mediation of oviposition by the phlebotomine sandfly Lutzomyia longipalpis. AB - Extracts of rabbit food, hay and rabbit faeces elicited a positive oviposition response from gravid female Lutzomyia longipalpis sandflies (Diptera: Phlebotominae). Combined extract of rabbit food and oviposition pheromone had a synergistic effect on sandfly egg-laying, greatly increasing the number of eggs laid and resulting in a highly targeted response. Individually tubed flies, exposed to the combined extract, were shown to be 3.5 times more likely to survive oviposition and laid 2.5 times more eggs than control flies. A laboratory oviposition trap baited with the combined extract was tested in a cage and caught 31 (62%) of 50 gravid L. longipalpis over a 72h period. PMID- 8369557 TI - Bloodmeal digestion in the midgut of Phlebotomus papatasi and Phlebotomus langeroni. AB - Bloodmeal digestion in midguts of the sandflies Phlebotomus papatasi and Phlebotomus langeroni (Diptera: Psychodidae) was investigated in optimized assays to detect general protease, trypsin and aminopeptidase activities using synthetic substrates. Optimal activity occurred at pH 8-9 for all enzymes examined in both species. Protease activity peaked at 24-34 h post human bloodmeal in midguts of P. papatasi and 34-48 h in P. langeroni; all endo- and exoprotease activities were completed by 50 h in P. papatasi compared to 72 h in P. langeroni. Hydrolysis of two chymotrypsin substrates was < 2% of trypsin activity in both species. Aminopeptidase activity was associated mainly with the midgut wall, whereas trypsin activity was confined to the midgut lumen. A feature of digestion in P. langeroni was the high level of aminopeptidase recorded within 10 h of the bloodmeal. PMID- 8369558 TI - Comparison of five tests for the serologic diagnosis of myiasis by Gasterophilus spp. larvae (Diptera: Gasterophilidae) in horses and donkeys: a preliminary study. AB - Sera from 41 horses and 159 donkeys, from twelve States of Mexico, were tested to ascertain anti-Gasterophilus circulating antibodies by double immunodiffusion (DD), counterimmunoelectrophoresis (CIE), indirect haemagglutination (IH), thin layer immunoassay (TIA) and diffusion-in-gel ELISA (DIG-ELISA) methods using crude somatic antigen from third instar larvae of G. intestinalis (DeGeer). At necropsy, 33/41 horses and 24/159 donkeys were found to be parasitized by G. intestinalis and/or G. nasalis (L.). Gasterophilus intestinalis was the species most commonly found in the equines. Analysis of the sera from the infected animals by DD showed positive results of 21.2% in horses and of 8% in donkeys. Screening the sera with CIE gave sensitivities of 69.7% in horses and of 32% in donkeys. Examination of the sera by IH showed positive results of 87.9% and of 48% in horses and donkeys, respectively. Testing the sera with TIA gave sensitivities of 93.9% in horses and of 96% in donkeys. Analysis of horses' sera by DIG-ELISA showed a sensitivity of 93.9%. PMID- 8369559 TI - Climate, satellite imagery and the seasonal abundance of the tick Rhipicephalus appendiculatus in southern Africa: a new perspective. AB - Recent predictive models for the distribution of the African tick Rhipicephalus appendiculatus Neumann, based on the computer packages CLIMEX and BIOCLIM and data derived from meteorological satellites, and for the seasonal dynamics of the same tick using the computer simulation models ECFXPERT and T3HOST, all have their limitations. Statistical analysis of the relationships between the seasonal abundance of all three life stages of this tick and climatic and satellite derived data from five sites in southern Africa, taken from the literature, supports a new perspective that it is the timing of the questing activity of the desiccation-vulnerable larvae that determines the pattern of the tick's seasonal dynamics. The timing of the activity of nymphs and adults is determined by temperature-dependent development rates plus the delaying phenomenon of photoperiod-sensitive diapause, the timing and duration of which have evolved to achieve maximum generation survival by ensuring the occurrence of eggs and larvae during periods of optimal climatic conditions. The most important environmental factor appears to be night-time minimum temperature, determining condensation and saturation deficit and thus the tick's ability to replenish moisture lost during the daytime and so to survive while questing for hosts. It is the larvae whose numbers are correlated most closely with these factors, consistent with earlier experimental results showing larvae to be most susceptible to desiccating conditions. There is a statistical linkage between larval tick numbers and satellite imagery, arising from the correlation between larval numbers and minimum temperature and saturation deficit conditions, and in turn the relationship between these climatic conditions and the subsequent vegetational changes monitored by the satellites. Moisture availability to larvae is likely to be the critical factor throughout the geographical range of R. appendiculatus, but the precise combination of climatic conditions that optimize moisture availability and questing tick survival can be expected to vary geographically. The relationships between ticks, temperatures and satellite data in parts of equatorial Africa have yet to be established. These correlative patterns highlight both the critical life stage and environmental factors when trying to understand temporal, and ultimately spatial, variations in tick abundance. PMID- 8369561 TI - Scanning electron microscopy of the larval instars of Cochliomyia hominivorax. AB - Descriptions are given of the morphological features of laboratory-reared first to third larval stages of Cochliomyia hominivorax. The pseudocephalon, spines and papillae of the segments, and the anterior and posterior spiracles of all three larval stages were studied by scanning electron microscope microscope. PMID- 8369560 TI - Diethylphenylacetamide: a new insect repellent against stable fly, Stomoxys calcitrans. AB - This paper reports the results of a laboratory study showing effectiveness of a new insect repellent N,N-diethylphenylacetamide (DEPA) against stable fly, Stomoxys calcitrans, and compared to N,N-diethyl-m-toluamide (DEET) and dimethyl phthalate (DMP). DEPA gave maximum protection time of more than 6 h at 3% concentration followed by DEET and DMP. PMID- 8369562 TI - Effects of the fungus Aspergillus penicillioides on the house dust mite Dermatophagoides pteronyssinus: an experimental re-evaluation. AB - In this report the widely-held view that house dust mites benefit from fungal contamination of the dietary substratum is re-examined. The performance of Dermatophagoides pteronyssinus (Acari: Pyroglyphidae) is documented over two successive generations in the presence or absence of the xerophilic fungus Aspergillus penicillioides (Hyphomycetales: Moniliaceae). This fungus reduced survival, development rate, adult length and fecundity of D. pteronyssinus. Detrimental effects of A. penicillioides were proportional to the fungal density. Despite the antagonistic effects of A. penicillioides, a requirement for the fungus was indicated by the poor performance of fungus-free mites in the second generation; sustained culture of D. pteronyssinus in the absence of fungi is probably not possible. It is suggested that fungi may alter the particulate nature of the substratum to the detriment of house dust mites, but also provide micronutrients deficient in the diet. PMID- 8369563 TI - Characterization and description of a virus causing salivary gland hyperplasia in the housefly, Musca domestica. AB - A double-stranded DNA virus was isolated from hyperplasic salivary glands of male and female houseflies, Musca domestica L. (Diptera: Muscidae), collected from a dairy in Alachua County, Florida, U.S.A. Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE) of this housefly salivary gland hyperplasia (SGH) virus revealed the presence of two major and eight minor structural polypeptides. Restriction endonuclease analysis indicated that the c. 137 kilobase pair DNA was double-stranded. Weekly, sweep-net sampling of the fly population throughout the season (May-October, 1991) showed that 1.5-18.5% of the dissected flies possessed hyperplasic salivary glands. The virus replicated within the nuclei of the salivary gland cells and was transmitted per os to newly emerged healthy adult flies. PMID- 8369564 TI - Vertical transmission of Toscana virus in the sandfly, Phlebotomus perniciosus, via the second gonotrophic cycle. PMID- 8369565 TI - Temperature-related activity loss and mobility changes of esterases associated with insecticide resistance in Culex pipiens mosquitoes. PMID- 8369566 TI - Gonotrophic status of female phlebotomine sandflies collected by three different methods in Kenya. PMID- 8369567 TI - Leishmania donovani infections in phlebotomine sandflies from the kala-azar focus at Aba Roba in Ethiopia: DNA probe compared with conventional detection methods. PMID- 8369568 TI - Temperature-induced refractoriness of Aedes aegypti mosquitoes to infection with the filaria Brugia pahangi. PMID- 8369569 TI - Distribution and taxonomic status of chromosomal forms of the onchocerciasis vector Simulium exiguum in central Ecuador. PMID- 8369570 TI - Malaria sporozoite rates in Anopheles mosquitoes: theoretical comparability of salivary gland dissection with the ELISA detection method. PMID- 8369571 TI - Thermal behavior of a human glioma cell line and its response to combinations of hyperthermia and lonidamine. AB - The effect of hyperthermia and lonidamine, alone and in combination, on the clonogenic activity of a human glioma cell line was investigated. The time temperature relationship of asynchronous, exponentially growing cells was defined in the range of 40-45 degrees C. All survival curves were exponential and an Arrhenius plot for heat killing was linear over the temperature range tested, with an activation energy of 192 Kcal/mol. The survival curve of lonidamine treated cells was also exponential after an initial shoulder. The analysis of the interaction between lonidamine and hyperthermia, performed by the isobolar method, demonstrated an additivity of response so that the effectiveness of the combined treatment was the result of two independent effects. Lonidamine inhibits the neoplastic growth mainly through an ATP depletion, but the thermal killing was not mediated by the drug-induced changes in the energy status of the cell. The effectiveness of the combined treatment was strongly influenced by the schedule of administration. In fact, the sequence lonidamine-->hyperthermia made the cells less sensitive to heat so that the pre-established end-point, i.e. 30% survival, was never achieved whichever combination was used. This "drug-induced heat resistance" was not associated with the induction of heat shock proteins, but rather with modification of cell cycle. On the contrary, showing a purely additive effect, the sequence hyperthermia-->lonidamine allowed achievement of the pre-established cell killing (70%), with exposure times (1-2 hr) and with a temperature (42 degrees C) generally accepted as clinically achievable. Therefore, also considering its low systemic toxicity, lonidamine may be useful in reducing the side effects of hyperthermia. PMID- 8369572 TI - Patterns of expression of metalloproteinases and their inhibitors in human malignant lymphomas. AB - Forty-two cases of malignant lymphomas were studied for the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) by Northern blot and in situ hybridization. The lymphomas were classified according to Working Formulation classification (25 high grade, 15 low grade, and 2 intermediate grade). The MMPs studied included: 72-kDa and 92-kDa gelatinases (type IV collagenases), interstitial collagenase, PUMP-1 (MMP-7), and stromelysins 1 and 3. TIMPs included TIMP-1 and TIMP-2. All but one case expressed TIMP-1, and TIMP 2 transcripts were detected in 35 cases. Among the MMPs, 92-kDa gelatinase was expressed most consistently (35 cases), whereas mRNA transcripts of 72-kDa gelatinase, interstitial collagenase, and PUMP-1 were detected in only a few cases. Stromelysins 1 and 3 mRNAs were not detected in any of the tumors studied. However, marked differences in the level of expression of certain MMPs and TIMPs were found among different grades of malignant lymphomas. The low grade tumors expressed low and relatively constant levels of TIMP-1, TIMP-2, and 92-kDa gelatinase transcripts, whereas high grade lymphomas displayed variable amounts of mRNAs for TIMPs and MMPs, with a trend toward elevated TIMP-1 and 92-kDa gelatinase mRNA levels. In situ hybridization localized TIMP-1 transcripts to stromal cells, while 92-kDa gelatinase transcripts were most abundant in "starry sky" macrophages and large lymphoma cells. Zymography showed that active 92-kDa gelatinase is present in tumor protein extracts and differences in the level of the enzymatic activity were seen between low and high grade lymphomas. Our data indicate that 92-kDa gelatinase and TIMP-1 expression by human malignant lymphomas may play an important role in controlling their biologic aggressiveness. PMID- 8369573 TI - 2-Alkylsulfonyloxy-3-hydroxy-1,4-naphthoquinones: a novel class of radio- and chemosensitizers of V79 cells. AB - Four 2-alkysulfonyloxy-3-hydroxy-1,4-naphthoquinone derivatives, VH(1-4), have been synthesized as a novel class of bioreductive alkylating agents and tested as hypoxic cytotoxins, radiosensitizers, and chemosensitizers of V79 cells. In this series, the naphthoquinone is the bioreductive moiety while the sulfonyloxy group, as a good leaving group, could lead to alkylations of nucleophilic substrates in the cells. All VH-compounds are moderately selective cytotoxins of V79 cells with a differential aerobic-hypoxic toxicity of approximately 2, i.e. ratio of drug concentrations to give 50% killing for aerobic versus hypoxic cells. All derivatives are radiosensitizers of hypoxic V79 cells but only VH-3 can give a sensitization enhancement ratio of 2.05 at a nontoxic concentration. Finally, all VH-derivatives are good chemosensitizers of V79 cells to the aerobic toxicity of melphalan, either under hypoxic preincubation without melphalan or under aerobic coincubation with melphalan. The dose modification factors were approximately 2, at low, non-toxic concentrations. PMID- 8369575 TI - Reference listings in cancer research. PMID- 8369574 TI - Apoptosis (programmed cell death) and the evaluation of chemosensitivity in chronic lymphocytic leukemia and lymphoma. AB - Chronic lymphocytic leukemia and lymphoma cells were treated with antitumor drugs in vitro and analyzed by flow cytometry to measure the number of apoptotic (AP) cells and DNA damage in the cells that escaped apoptotic death. AP cells were identified by a high sensitivity of DNA to thermal denaturation, which induced binding of antibody to single-stranded DNA, and by decreased stainability of cells with the intercalating DNA dye propidium iodide. The appearance of AP cells was prevented by Zn++ and inhibited by phorbol ester. AP cells were induced by alkylating agents, antimetabolites, and anthracyclines. A linear relationship between L-phenylalanine mustard dose and the number of AP cells was observed. A synergistic interaction between drugs was detected by an increased number of AP cells and by the intensity of DNA damage in non-apoptotic cells. A most interesting example of synergism was the combination of alkylating agents with fludarabine. Linearity of dose-response curves, and the capability to detect drug synergism and to evaluate variable response of cells from different patients to single agents and combinations suggest that flow cytometry of apoptosis will provide a basis for chemosensitivity tests in leukemia and lymphoma. PMID- 8369576 TI - Short- and long-term considerations concerning the management of plaque psoriasis with low-dose cyclosporin. Studio Italiano Multicentrico nella Psoriasi (SIMPSO). AB - In an open multicenter study, cyclosporin (CsA) at low doses (3 mg/kg/day adjusted during the course of treatment on the basis of clinical response and tolerability up to a maximum of 5 mg/kg/day) was given to 293 evaluable patients with severe plaque-form psoriasis (M/F 215/78, aged 19-80 years, 2-53 years from diagnosis) in order to evaluate its safety and efficacy over a median follow-up of 7 months of treatment and 3 months after treatment. All patients were unsatisfactory responders to conventional topical therapy and had indications for systemic treatment. Patients entered the study only if they were within the normal range for renal and hepatic function and blood pressure, and were free of any clinically obvious immunodeficiencies, malignancies or blood dyscrasia. All gave their informed consent. After remission (defined as reduction > or = 75% of the body area involved and an improvement of at least 2 points on a 4-point scale for desquamation, erythema and infiltration) CsA was slowly tapered off (0.5 mg/kg/day every 2 weeks) until total discontinuation or the reappearance of signs of the disease; the dose of CsA was also varied in the case of any important modification in renal and hepatic function of blood pressure. As concomitant treatment, white petrolatum was allowed, as well as specific local therapy after CsA discontinuation. Considerable improvement (> 50% reduction in the skin area affected) was observed in 98%, and only 2% (5 patients) did not respond. Clinical remission was achieved in 225 patients (77%): of these, 73% after a median of 2 months at CsA doses of 2.5-3.49 mg/kg/day, 8% after 4 months at doses < or = 2.49 mg/kg/day and 19% after 3 months at doses > or = 3.5 mg/kg/day. After remission, the gradual withdrawal of the drug over a period of 3 months (0.5 mg/kg/day every 2 weeks) allowed control over the disease (the absence of relapse) to be maintained for a median of 8 months in 133 patients (59%). The topical therapies permitted after remission and during the maintenance phase (steroids, inert topical agents and exposure to UVB radiation) were used in less than 50% of cases. Disease relapse (the reappearance of skin involvement over more than 50% of the area affected at baseline) occurred in 92 of the 225 patients achieving remission, 24 of whom relapsed a median of 6 months after remission, when CsA had been completely withdrawn; the remaining relapses occurred about 4 months after remission, during the gradual withdrawal of the drug.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8369577 TI - Management of erythrodermic psoriasis with low-dose cyclosporin. Studio Italiano Multicentrico nella Psoriasi (SIMPSO). AB - Thirty-three patients (M/F 25/8, aged 19-71 years) with severe erythrodermic psoriasis entered an open multicenter study to evaluate the efficacy (induction and maintenance of clinical remission) and toleratility of long-term treatment with cyclosporin. It was given at a maximum initial dose of 5 mg/kg/day (initial mean dose 4.2 mg/kg/day), subsequently adjusted during the course of treatment according to clinical response, patient tolerability and any modification in laboratory parameters or blood pressure, carefully monitored each month. All of the patients were unsatisfactory responders to conventional systemic therapy (PUVA therapy, retinoids, corticosteroids), free of any clinically obvious immunodeficiencies, malignancies or blood dyscrasia and within the normal range for renal and hepatic function and blood pressure. At remission (defined as complete resolution of erythema in the body area involved), cyclosporin was slowly tapered off (0.5 mg/kg every 2 weeks) until total discontinuation or the reappearance of signs of disease. As concomitant therapy, white petrolatum in association with cyclosporin as well as specific local therapy between cyclosporin cycles was allowed. After 6.3 +/- 3.4 months (mean +/- SD), cyclosporin doses of 3-5 mg/kg/day had led to complete remission in 67% of patients (22/33) in a median time of 2-4 months; in a further 27% of cases, considerable improvement in skin involvement was observed, with a reduction of more than 70% in comparison with baseline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369578 TI - Cyclosporin therapy in psoriasis: recommendations for treatment. Italian Multicenter Study Group on Cyclosporin in Psoriasis. PMID- 8369579 TI - Cyclosporin versus etretinate: Italian multicenter comparative trial in severe plaque-form psoriasis. Italian Multicenter Study Group on Cyclosporin in Psoriasis. AB - Seventy-six patients with severe diffuse plaque-form psoriasis and a baseline PASI score > or = 18 were enrolled in a randomized open study comparing cyclosporin 5 mg/kg/day (36 patients) with etretinate 0.75 reduced to 0.5 mg/kg/day (40 patients) over a period of 3 months (phase 1). The rate, severity and time to relapse after the withdrawal of therapy in the 54 patients achieving remission were evaluated over the following 6 months (phase 2). Twelve of these patients entered an open, uncontrolled phase aimed at defining the safety and the strategy of cyclosporin 2.5-5 mg/kg/day maintenance therapy over a further period of 9 months (phase 3). Patient tolerability, laboratory parameters and blood pressure were carefully monitored every week for the first 3 months and then monthly. The only concomitant therapy allowed was white petrolatum. Not only the number (35/36 vs. 29/40) but also the speed of remission (20/36 vs. 1/40 at the fourth week of treatment) was higher in the cyclosporin than in the etretinate group. Both the tolerability and safety of cyclosporin proved to be adequate for short-term treatment, all altered clinical or laboratory parameters being completely reversible after the withdrawal of therapy. Only 1 of the 36 patients in the cyclosporin group prematurely stopped taking the medication because of an adverse reaction, as against 7/40 in the etretinate group (1 case of inefficacy, 1 case of adverse reaction and 5 cases of non-compliance). Six months after the discontinuation of the trial drugs, relapses occurred in 13/29 patients in the cyclosporin group and in 3/25 in the etretinate group; no 'rebound' was observed in any of the relapsing patients. Long-term cyclosporin treatment was both efficacious and well tolerated. In conclusion, cyclosporin at doses of 2.5-5 mg/kg/day administered to reliable, carefully selected patients closely monitored in terms of both clinical and laboratory parameters currently produces the quickest and more constantly favourable results in patients with severe psoriasis. PMID- 8369580 TI - Characterization of the family Pasteurellaceae on the basis of cellular lipids and carbohydrates. AB - Selected strains representing established and newly described taxa in the family Pasteurellaceae were investigated for their cellular lipid and carbohydrate composition to clarify the taxonomic significance of such features. Methylated cellular fatty acids and acetylated derivatives of the cellular carbohydrates were determined by capillary gas chromatography using a flame ionization detector. In part the carbohydrates were identified by mass spectrometry. Phospholipids were determined by thin layer chromatography, the lipoquinones by high pressure liquid chromatography. The cellular fatty acid patterns proved to be uniform with minor variations, but the separation from the Neisseriaceae and from Moraxella was possible. Also the distribution of the phospholipids was uniform within the family. The lipoquinone contents were useful for the discrimination of groups within the family not necessarily reflecting the degree of genomic relatedness. The analysis of the cellular carbohydrates resulted in a common sugar pattern with all members of the family and characteristic carbohydrate profiles discriminating groups, often to the species level. All of the cytochemical features considered were useful for the characterization of the family Pasteurellaceae. PMID- 8369582 TI - Classification of Pasteurella field strains isolated from farms in Germany using traditional methods and DNA-DNA hybridization. AB - 410 Pasteurella (P.) field strains isolated from calves and piglets were classified according to Bisgaard et al. (1). 376 strains were assigned to P. multocida ssp. multocida, 34 of them were ornithine- and trehalose+, and 61 of them ornithine- and trehalose-. 4 strains belonged to P. multocida ssp. septica, 4 to P. multocida ssp. gallicida, 6 to P. avium biovar 2 and 20 to P. canis biovar 2. There was no difference in the prevalence of the species in calves and pigs. The fact that strains belonging to P. multocida ssp. septica were isolated only from calves and P. multocida ssp. multocida ornithine- and trehalose- were mostly isolated from piglets could indicate a certain host specificity of these isolates. In genotypic investigations 20 field isolates of P. multocida belonging to different Carter serotypes, as well as serologically negative strains were compared to reference strains in terms of deoxyribonucleic acid (DNA) relatedness. The data obtained by filter hybridization revealed a considerable degree of genotypic intraspecies heterogeneity within P. multocida. No correlations to the respective serotypic classification could be detected. PMID- 8369581 TI - Prevalence and biochemical properties of V factor-dependent Pasteurellaceae from rodents. AB - Organs of 1436 rats and 2839 mice were monitored for V-factor dependent Pasteurellaceae. Such bacteria were isolated from 21.2% of rats and from 2.4% of mice, respectively. They were most frequently cultured from the deep respiratory tract (lungs and trachea). In addition, they were found in the nasal cavity and on mucous membranes of the genital and the intestinal tract. 35 phenotypical criteria were determined for 429 isolates. Based on these data, groups of bacteria showing similar biochemical properties were formed using exploratory statistical methods (principal qualitative analysis). The majority of 333 isolates is represented in a rather homogenous group which has some characteristics in common with the Haemophilus parainfluenzae complex. The remaining isolates consist of several groups. It was shown by others that some of these bacteria are closely related to the yet unnamed Taxon B which forms a genus like cluster together with Pasteurella pneumotropica type Jawetz. PMID- 8369583 TI - Epidemiology of human infections by Pasteurella and related groups in France. AB - A retrospective study of infections due to Pasteurella (P.) and related groups was performed between the Pasteurella National Center and Nancy's hospital from 1985 to 1991. Among the 958 cases recorded, wound infections (bites, scratches and punctures) were the common forms of pasteurellosis (66%) caused by P. multocida (48%), P. canis (11%), P. dagmatis (5%), P. stomatis (4%), and in few cases by groups EF-4 and M-5 (14 and 13%, respectively). In human infections unrelated to animal wounds, respiratory tract diseases and bacteremia-septicemia were the predominant infections with respectively 19 and 11%, and caused by P. multocida. Next in importance were urogenital (2.5%), abdominal (1%) and central nervous system (< 1%) infections. The majority of animal bite wound infections was treated with penicillins or tetracyclines; with other forms, penicillins and cephalosporins were more likely. PMID- 8369584 TI - Isolation and characterization of group EF-4 bacteria from various lesions in cat, dog and badger. AB - Bacteria of Group EF-4 were isolated from local purulent lesions in 7 dogs and in 5 cats, from pneumonic lungs in 2 additional cats and from internal organs in a badger. Results of characterization were compared with those of a human strain of Group EF-4a isolated from an infected dog-bite wound. Lungs of 2 necropsied cats showed a severe focal necrotizing pneumonia in the various lobes. Organs of the badger were typical for a case of septicemia. The organisms were isolated mostly in pure culture. Colonies were up to 1.5 mm in size, round, entire, more or less yellowish pigmented and non hemolytic. Culture smelled slightly like popcorn. In conventional biochemical tests, 12 isolates as well as the human strain were shown to belong to Group EF-4a and the 3 remaining strains to EF-4b. Belonging to Group EF-4 was confirmed by assimilation tests with the gallery ATB 32 GN of BioMerieux. However some differences to other reports were observed when compared with results obtained with similar methods. Results of this study seem to indicate that bacteria of Group EF-4 are important in veterinary medicine not only from an epidemiological but also from an etiological point of view. PMID- 8369585 TI - Ecology and significance of Pasteurellaceae in man--an update. AB - Within the last decade new knowledge has emerged concerning the significance of Pasteurellaceae in man; the classification has undergone some changes, and new taxa were described. Haemophilus influenzae serotype b was shown to have a clonal distribution that is related to demographic patterns of the human host. Brazilian purpuric fever is caused by a special clone of Haemophilus aegyptius. H. influenzae biotype IV seems to be a genital pathogen, and may deserve species rank. New Pasteurella species have been described, that occur in well known pathological foci in man, e.g. bite wounds. Toxigenic P. multocida may occur in man also; the significance of toxigenicity in man is not known. The real actinobacilli of man, A. ureae and A. hominis are still very rarely reported. In order to avoid wrong epidemiological conclusions, correct diagnosis is emphasized. PMID- 8369586 TI - Detection of an adenylate cyclase gene in Pasteurella species. AB - A Pasteurella multocida adenylate cyclase gene has been previously cloned in Escherichia coli and sequenced. A 1200 bp HpaI fragment from the coding region was used as a probe to analyse the presence of the gene in different Pasteurella species and subspecies, Actinobacillus ureae (formerly P. ureae) and group EF-4 bacteria. Thirty-seven strains were checked for the presence of the gene. It was shown that the adenylate cyclase gene was detected only in the species Pasteurella multocida. PMID- 8369587 TI - Ecology and significance of Pasteurellaceae in animals. AB - The reservoir of eighty-one taxa/groups classified with the family Pasteurellaceae Pohl 1981 is reviewed based upon published data and own investigations. With the exception of certain strains of P. multocida, A. pleuropneumoniae and [H.] paragallinarum organisms belonging to this family are usually regarded as opportunistic, secondary invaders which under normal conditions coexist peacefully with the animal host on mucosal membranes of the upper respiratory- and lower genital tracts. Very little is known about factors that govern the ecological preferences that certain members of this family show for specific surfaces and hosts. Mechanisms of colonization, survival and multiplication, invasion and pathogenic action are incompletely understood. The significance of Pasteurellaceae in animals and man has recently been reviewed. Subsequent publications have underlined the significance of biovars 2 of P. canis and P. avium and ornithine negative P. multocida in pneumonia in cattle. In addition, differences in pathogenicity have been demonstrated for different serovars of [H.] parasuis. The disease potential of many taxa/groups is only incompletely known. PMID- 8369588 TI - Genetic analysis of Actinobacillus pleuropneumoniae, and comparison with Haemophilus spp. Taxon "minor group" and Taxon C. AB - The genetic diversity among 52 field isolates, mainly from Australia, and 15 reference strains of Actinobacillus pleuropneumoniae was examined using multilocus enzyme electrophoresis. Thirty three electrophoretic types (ETs) were recognised, with a mean genetic diversity per locus of 0.312. Australian strains of serovars 1, 2, 5 and 7 belonged to the same clonal lines as strains of these serovars in other countries, but distinct clones of serovars 3, 7, 11 and 12 were also identified. The type strains of serovars 1, 9 and 11 were placed in the same ET. Strains of A. pleuropneumoniae biovar 2 were closely related to biovar 1 strains. Twenty three isolates which did not react with the typing sera or could not be assigned to a single serovar were divided into seven clonal groups. Five strains of Haemophilus sp. Taxon "minor group" which were included in the study were distinct from A. pleuropneumoniae, and were diverse, being divided into at least two major genetic groupings. Two strains of Haemophilus sp. Taxon C were placed in another distinct ET. PMID- 8369589 TI - Whole cell protein profiling of actinobacillus-like strains classified as taxon 2 and taxon 3 according to Bisgaard. AB - Thirty-nine strains representing all biovars established within the taxa 2 and 3 complex of Bisgaard and two strains belonging to the avian [P.] haemolytical[A.] salpingitidis complex were characterized by one-dimensional SDS-PAGE of cellular proteins. The protein patterns, which contained 40 to 45 discrete protein bands, were highly reproducible. Numerical analysis of the background protein patterns obtained resulted in six major and twelve minor groups (phena). Comparison of the phena defined by protein profiling with species/groups previously established by DNA: DNA hybridization, chemotyping and "biotyping" showed that the best correlation existed between DNA:DNA hybridization and "biotyping". A correlation between results obtained from DNA:DNA hybridization and protein profiling was not obtained. With a few exceptions, a connection was demonstrated between protein profiles and hosts from which the strains belonging to the respective phena originated. PMID- 8369590 TI - Aspirin and the elderly. Current status. PMID- 8369591 TI - Prescribing policy for antiulcer treatment in the elderly. AB - In the short and long term treatment of peptic ulcer in the elderly some problems have yet to be resolved, mainly concerning the physiology and pathophysiology of the aging stomach, the pharmacokinetic and pharmacodynamic properties of antiulcer drugs, and the presence of different risk factors compared with young patients. The available data from controlled trials of peptic ulcer in the general population and from the limited experience in geriatrics, show that the clinical efficacy and tolerability of the anti-secretory drugs (e.g. cimetidine, ranitidine and famotidine) and of cytoprotective compounds are similar to that observed in younger patients. However, more data are necessary concerning the optimal dosage in relation to physiological age-related changes of liver and kidney function, the duration of prophylactic treatment, and importantly, the assurance of adequate patient compliance. PMID- 8369592 TI - Physiological changes due to age. Implications for drug therapy of congestive heart failure. AB - The segment of the population considered to be 'elderly' is consistently growing. At the same time, the number of patients with congestive heart failure continues to grow. Therefore, it is important to consider whether older patients with congestive heart failure have characteristics that identify an aging effect in addition to the obvious abnormalities produced by heart failure. Furthermore, it is important to determine the relevance of these abnormalities to the use of pharmacological therapy. Within a population of 128 consecutive heart failure patients, age-related increases of systemic vascular resistance, changes in baroreceptor responses, and increases of plasma noradrenaline (norepinephrine) levels were identified. In addition, an age-related reduction of renal function was clearly evident in patients > 65 years of age. These changes affect the use of digoxin, diuretics and angiotensin converting enzyme (ACE) inhibitors. Most notably, marked reduction of renal function in such patients must be considered in the drug treatment of heart failure. PMID- 8369593 TI - The problems of anticholinergic adverse effects in older patients. AB - The old saying 'red as a beet, dry as a bone, blind as a bat, hot as a hare, mad as a hatter' is often quoted when describing the autonomic effects of drugs that block the muscarinic cholinergic system. These effects may be subtle or dramatic, yet can be overlooked or discounted as a natural consequence of old age. Elderly patients can be particularly sensitive to the anticholinergic action of drugs because of physiological and pathophysiological changes that often accompany the aging process. The use of multiple drugs, a common finding in older patients, may result in pharmacodynamic and pharmacokinetic drug interactions that heighten anticholinergic effects. While the classic anticholinergic problems of decreased secretions, slowed gastrointestinal motility, blurred vision, increased heart rate, heat intolerance, sedation and possibly mild confusion, may be uncomfortable for a younger patient in relatively good health, these effects can be disastrous for older patients. Even the most common peripheral anticholinergic complaint of dry mouth can reduce the ability to communicate, predispose to malnutrition, promote mucosal damage, denture misfit or dental caries, and increase the risk of serious respiratory infection secondary to loss of antimicrobial activity of saliva. Mydriasis and the inability to accommodate will impair near vision and may precipitate narrow angle glaucoma in predisposed patients, but less obviously could lead to an increased risk of accidents, including falls. Somatic complaints of constipation and urinary hesitancy, could, in the presence of anticholinergic challenge, result in faecal impaction or urinary retention. Cardiac effects may be poorly tolerated. Increases in heart rate may precipitate or worsen angina. Finally, thermoregulatory impairment induced by anticholinergics, which block the ability to sweat, may lead to life threatening hyperthermia. Central anticholinergic effects range from sedation, mild confusion and inability to concentration to frank delirium. Even mild effects can reduce function and increase dependency. At any level of care, the loss of independence increases the caregiver burden, costs, and most importantly, can negatively affect quality of life. Many age-related and disease-related conditions may predispose elderly patients to anticholinergic drug toxicity. Careful attention to anticholinergic effects when prescribing drugs, patient education, regular review of the entire drug regimen, and familiarity with the signs and symptoms of anticholinergic toxicity will help to reduce the risk of drug-induced problems. PMID- 8369595 TI - A critical review of admission and discharge medications in an elderly Australian population. AB - Medications were examined on admission to and discharge from hospital in an elderly population. Polypharmacy was documented. Patients were discharged on more medications (4:7) than they were taking prior to admission (4.1). This was statistically significant in men (p < 0.001) but not women. Multiple medication changes were undertaken. Admission drug regimens perceived by patient, admitting hospital doctor and general practitioner were also compared. Of 64 patients who were able to name their medications, only 64% described the same list as admitting doctors and only 43% described the same list as general practitioners. Hospital doctor and general practitioner lists were the same in only 37% of cases. Communication between these 3 groups needs to be optimised. PMID- 8369594 TI - Drug-induced cognitive impairment. Defining the problem and finding solutions. AB - Drug-induced cognitive impairment is a common cause of delirium and is frequently a confounding factor in dementia. Predisposing conditions for delirium include age, brain disease and addiction to alcohol and/or drugs. The elderly are at particular risk because of multiple diseases, multiple drug use and alterations of drug metabolism associated with age. Sedatives such as benzodiazepines have a particularly high risk of cognitive impairment. Centrally acting sympathetic antihypertensive agents, sedating antipsychotic drugs, opioids, digitalis, anti Parkinsonian drugs, antidepressants and corticosteroids are also associated with greater risk relative to other classes of medications. Cognitive impairment due to medication may be reduced by recognition of the problem. The risk of drug induced impairment may be minimised by strategies which optimise overall health, avoidance of unnecessary medications, and selection of medications least likely to cause delirium. PMID- 8369597 TI - Simulations of passive properties and action potential conduction in an idealized bullfrog atrial trabeculum. AB - This study investigates the properties of a distributed parameter model of an idealized trabeculum of cardiac muscle surrounded by a resistive-capacitive trabecular sheath. A mathematical approach is developed that permits the direct solution for the absolute potential in each medium [i.e., the intracellular (Vi), interstitial (Ve), and external (Vo) potentials), as opposed to obtaining solutions for the transmembrane potential V (where V identical to Vi-Ve). The mathematical description of the underlying individual cell is based upon quantitative whole-cell voltage-clamp measurements in bullfrog atrial myocytes. "Reduced" or "simplified" cell membrane models that lack the complete complement of transmembrane currents are compared with regard to their accuracy in representing the root, upstroke, and plateau regions of the propagated action potential in the complete model. The results show that a reduced cell membrane model must contain the sodium current INa, calcium current ICa, and background rectifying K+ current IK1. A cell membrane model that contains a linear background K+ current IL instead of IK1 results in much poorer approximation to the upstroke, plateau, and conduction velocities of an action potential. The effects of varying the resistive-capacitive parameters of the trabecular sheath on both the passive properties (the time and space constants and the input resistance) and conduction parameters (time and space constants of the foot and conduction velocity of the action potential) of the trabeculum are also investigated. These simulations show that electrical activity within the trabeculum is much more sensitive to variations in the resistive component than in the capacitive component of the sheath. The trabecular sheath reduces the extracellular resistance seen by the cell by shunting current away from highly resistive interstitial medium into the volume conductor medium, which is of low resistance, and thereby increases conduction velocity. Finally, the addition of the cholinergic neurotransmitter acetylcholine to the extracellular medium reduces both the space constant of the trabeculum and the conduction velocity of propagated electrical activity. PMID- 8369598 TI - Distributed solute and water reabsorption in a central core model of the renal medulla. AB - In this model study we investigate the dependence of urine concentrating capability on the spatial distribution of solute and water reabsorption from Henle's loops. Within the context of model assumptions, urine concentrating capability is increased by exponential decline in loop population as a function of medullary depth and by solute efflux localized near loop bends, in accordance with earlier, but less comprehensive, studies. Further, we find that water impermeable prebend enlargements of the descending limb may release urine concentrating capacity that would otherwise be needed to concentrate the fluid flowing in the prebend enlargements. Calculations reported here suggest that without some distributed features, even vigorous net active transport of solute from the ascending limbs of the inner medulla would not be sufficient to explain the large concentration gradients generated by some mammals. We consider the significance of distributed reabsorption for the operation of the concentrating mechanisms of the mammalian inner medulla, the mammalian outer medulla, and the avian medullary cone. PMID- 8369599 TI - A stochastic model of hormesis. AB - In order to describe the life-prolonging effect of some agents that are harmful at higher doses, ionizing radiations in particular, a stochastic model is developed in terms of accumulation and progression of intracellular lesions caused by the environment and by the agent itself. The processes of lesion repair, operating at the molecular and cellular level, are assumed to be responsible for this hormesis effect within the framework of the proposed model. Properties of lifetime distributions, derived for analysis of animal experiments with prolonged and acute irradiation, are given special attention. The model provides efficient means of interpreting experimental findings, as evidenced by its application to analysis of some published data on the hormetic effects of prolonged irradiation and of procaine on animal longevity. PMID- 8369600 TI - Waves of extinction from sterile insect release. AB - Employing theoretical models, we show that the sterile insect release method (SIRM) can give rise to traveling waves of fertile insects. The velocity of these waves depends critically upon the density of sterile insects (and thus upon the rate at which sterile individuals are being released into the environment). When the sterile density is sufficiently low, the traveling wave advances, giving rise to an invasion. However, when the sterile density exceeds a critical threshold, the wave reverses direction, thereby retreating and giving rise to local extinction. Both analytical (regular perturbation) methods and numerical methods are used to determine wave velocities and wave profiles. This is the first time traveling wave solutions have been shown for the SIRM. PMID- 8369601 TI - [Assessment of the degree of disability in narcolepsy]. AB - This article sums up the scientific results of the past 10 years on narcolepsy reflecting its impact on socio-medical impairment of narcoleptic patients. Extensive epidemiological studies showed that major restrictions for narcolepsy patients are caused by daytime sleepiness and sleep attacks with consecutive cognitive and memory deficits high accident rates, personality, mood and sexual disorders. We suggest the minimum degree of impairment as a rule should be at least 50%, in case of drug-resistant cataplexy or permanent sleep attacks around 80%. PMID- 8369596 TI - Diltiazem. A review of its pharmacology and therapeutic use in older patients. AB - Diltiazem is a benzothiazepine derivative calcium antagonist available in several formulations, some of which enable once daily administration. The drug as monotherapy has demonstrated similar efficacy to diuretics in older patients with hypertension. Data comparing diltiazem with beta-blockers and angiotensin converting enzyme inhibitors are more limited, but available studies suggest at least comparable antihypertensive efficacy. Diltiazem as monotherapy or in combination with a beta-adrenoceptor-antagonist, isosorbide dinitrate, or another calcium antagonist, has demonstrated efficacy in patients with effort angina. The drug has also been used intravenously to terminate supraventricular tachycardias and to control the ventricular response to atrial fibrillation or flutter; it also appears to reduce the rate of early reinfarction in patients with non-Q-wave myocardial infarction. The most common adverse events during diltiazem therapy include headache, flushing, peripheral oedema and hypotension. Atrioventricular block although rare, is the most frequent serious adverse event related to diltiazem therapy and may be exacerbated by coadministration of beta-adrenoceptor antagonists, especially in the elderly. Thus, diltiazem appears to be an effective and well tolerated treatment for hypertension and angina in older patients and has shown promise as therapy for supraventricular tachycardias and as prophylaxis against early reinfarction in patients with non-Q-wave myocardial infarction. PMID- 8369602 TI - [Development, organization and evaluation of a public health surveillance system]. AB - Health professionals who set health policies and manage prevention and disease control programs are committed to the goals of reducing disease and injury related morbidity and mortality and improving the public's health and quality of life. To determine what health policies are needed and what specific actions should be taken and which epidemiological investigations should be carried out in order to identify lack of coverage of public health programs, decision makers need continuous information in order to tackle upcoming technical questions and to identify the most serious existing and emerging health problems of today's society. Both, political decision makers and health professionals have to ask themselves how those health problems can be prevented and which are the most cost effective prevention and control strategies for this purpose. Other important issues for the implementation of public health surveillance is the feasibility of available control strategies and their possible impact on different health outcomes. Alternative prevention and control activities have to be evaluated as how they meet the proposed objectives. Finally, remains the question, how scarce economic, material and human recourses should be allocated and targeted in order to achieve maximum impact for health goals. Only a sophisticated public health surveillance system can give answers to all those issues. Surveillance is defined as the ongoing systematic collection, analysis and interpretation of date on specific health events for use in planning, implementation and evaluation of public health programs. Timely dissemination of these data to persons who need to know is essential to effective prevention and control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369603 TI - [Effect of change in the occupational structure on extending life expectancy in Germany--a cohort analysis]. AB - Life expectancy in Germany has increased considerably during the 20th century. Simultaneously a considerable change in occupational structure has occurred. Keeping the occupational impact on mortality in mind, the question arises as to what extent the mortality decrease can be contributed to changes in occupation. Based on cohort data this question is analysed with the result that a considerable impact on life expectancy is confirmed. The impact of changes in occupational structure on life expectancy is greater for men than for women. This can be explained by the fact that men benefit from the improvements of general living conditions associated with occupational status, as well as from improved working conditions. PMID- 8369604 TI - [The status of maternally acquired tetanus immunity in newborn infants]. AB - In newborn and their mothers a considerable lack of immunity to tetanus was found. Values of corresponding serum pairs differed in part; some children were unprotected in spite of maternal immunity. Pregnant women without protection should therefore be vaccinated twice before delivery. Over and above this, good hygienic standards in obstetrics must be maintained. PMID- 8369605 TI - [Changes in suicide mortality in Germany]. AB - OBJECTIVE: About one third of the total number of life lost in the period between 1 and 65 years in consequence of "external causes" (E-classification by WHO) in East and in West Germany account alone for "suicide" as a cause of death. Suicide alone produces, e.g. among the male population, a loss in years of life which corresponds to 53% (in East Germany) and to 40% (in West Germany), respectively, of the total number of years of life lost due to cancer of all organic localizations. METHODS: The analysis is based on the official mortality data from 1961 to 1989. The data are analysed by age and sex. SMR, average age of death and PYLL are calculated. RESULTS: A comparative survey of suicide mortality over the period from 1961 to 1989 has shown that there are differences in suicide frequencies between East and West Germany. If related to the whole period, the lowest suicide rates both in the East and in the West have been observed at the end of that period. The suicide mortality rate in the East, however, remained higher than in the West, by 79.9% (male population) and by 70.2% (female population), respectively. The long-term trend is characterised by a slight increase of the suicide gap between East and West among the male population, whereas the difference has diminished in respect of the female population. Sex related differences are even more distinct than differences between East and West in suicide mortality. Thus, in 1989, the standardized suicide rates among the male population amounted to 2.7 times (West Germany) and 2.8 times (East Germany) of that of the female population, these differences having increased continually during the period from 1961 to 1989. CONCLUSIONS: The results cast justifiable doubts on whether the actual distribution of research capacities and of financial and personnel resources are adequate to cope with the problems raised by the phenomenon of "suicide". PMID- 8369606 TI - [Assessment of health effects of CS gas]. AB - O-chlorobenzylidene malononitrile (CS) gas or aerosol is by no means a harmless tear-gas, as often is described; in particular, CS is a very effective irritating war gas. The effects of CS on humans are relatively unknown because publications in this respect are mostly on military medical research, partly classified as secret, and brought to the knowledge of a small number of experts only. CS is highly soluble in water, and hence the effects in police water jets are very low. The efficacy of CS-containing water-jetting consists only in the pressure of the jet stream. Medically, in police use, CS is therefore considered to be harmless. Military medical research results, however, show that persons older than 30 years, those under physical strain, and those with hitherto undetected aneurysm are especially at risk. PMID- 8369607 TI - [The medical service of compulsory health insurance--quo vadis? The law, responsibility and interests of those involved]. AB - In contrast to all predictions and expectations the Medical Advisor of Health Insurance (MDK) still has to cope with an enormous quantity of medical examinations and reports. As long as the capacities of the MDK are completely absorbed by this task it cannot fulfill its legal commission as a medical consultant of the health insurance in an economical and highly qualified way. The present economical crisis of the health insurance can also be regarded as a challenge to overcome this situation. PMID- 8369608 TI - Preoperative diagnosis of malignant melanoma using the touch-fluorescence method. AB - We have developed a touch-fluorescence method using preparations from the outer surface of elevated and ulcerative malignant melanoma lesions. This method allows the demonstration of the melanogenic activity of melanoma cells within 30 min and has made it possible to definitively diagnose a lesion as malignant melanoma at the initial examination. In 21 cases clinically diagnosed as typical melanoma, 17 were definitively diagnosed as melanoma from the touch-fluorescence microscopic findings. Of the four cases in which no fluorescent tumor cells were found, two proved not to be melanoma. There was some correlation between the morbid types of primary melanoma and the configuration of fluorescent melanoma cells, the main cellular configuration of superficial spreading melanoma being round whereas that of nodular melanoma and acral lentigenous melanoma was pleomorphic. Based on the above results, this method was concluded to be extremely reliable for the preoperative diagnosis of elevated and ulcerative lesions of malignant melanomas, which are sometimes difficult to diagnose. PMID- 8369610 TI - Pulmonary oxygen transfer deficits of diabetic origin in patients undergoing coronary artery bypass grafting. AB - The objective of this study was to determine the effects of a diabetic disposition on pulmonary gas exchange by examining 72 patients who underwent coronary artery bypass grafting (CABG), using the arterial/alveolar oxygen tension ratio [(a/A)PO2] as a criterion. Patients were divided into a diabetic (DM) group and a nondiabetic (non-DM) group. The postoperative blood gases and hemodynamic data measured when the blood glucose level was at a maximum on the day of CABG were used as the postoperative pulmonary gas exchange indices, and the physicians who managed these patients were unaware of this study. The preoperative (a/A)PO2 ratio was 0.66 +/- 0.03 (SE) in the DM group and 0.78 +/- 0.02 in the non-DM group (P < 0.01), while the postoperative ratios were 0.42 +/- 0.03 and 0.52 +/- 0.03, respectively (P = 0.01). The correlation coefficient (r) for regression analysis of the relation between the postoperative PaO2/FIO2 ratio and the postoperative (a/A)PO2 ratio was 0.99 in the DM group (P < 0.01) and 0.88 in the non-DM group (P < 0.01). The r values of the relation between (a/A)PO2 and (A-a)PO2 were -0.68 (P < 0.00) and -0.84 (P < 0.01), while those for the respiratory index were -0.87 (P < 0.01), and -0.93 (P < 0.01), respectively. Thus, pulmonary oxygen transfer was compromised before and after CABG in the DM group compared to the non-DM group. Moreover, the PaO2/FIO2, being the simplest pulmonary gas exchange index to calculate, was a reliable substitute for the (a/A)PO2 ratio during the early postoperative management of CABG patients. PMID- 8369609 TI - Changes in plasma dopamine-beta-hydroxylase activity during the perioperative period of cardiac surgery: an index of sympathetic nerve activity. AB - To evaluate the usefulness of plasma dopamine-beta-hydroxylase (DBH) activity as an index of sympathetic nerve activity during cardiac operations, we examined the serial changes in plasma DBH activity, in relation to the plasma noradrenaline (NA) level and hemodynamic parameters, in patients who underwent cardiac surgery. The plasma DBH activity decreased significantly after cardiopulmonary bypass, and remained low during dopamine (DA) infusion until 72 h after the operation. However, recovery of the hemodynamic parameters, being the mean arterial pressure, heart rate and cardiac index, was seen as early as 1-3 h postoperatively. It was therefore assumed that the plasma DBH activity takes a long time to recover after an operation. The time-course changes in the plasma NA level were quite different from the changes in DBH activity, with an apparent negative correlation being observed between them. Thus, there is a possibility that exogenously administered DA, as well as increased plasma NA, might inhibit DBH activity during cardiac surgery. Moreover, since catecholamines are often administered upon completion of cardiac surgery, measurement of the plasma catecholamine level would be inappropriate for evaluating real sympathetic nerve activity. From the results of this study, it is surmised that measurement of the plasma DBH activity could be useful for estimating the intrinsic sympathetic nerve activity of patients who have undergone cardiac surgery. PMID- 8369611 TI - The psychological and cosmetic aspects of breast conserving therapy compared with radical mastectomy. AB - An evaluation of the psychological and cosmetic morbidity of 31 patients who had undergone breast conserving treatment (BCT group) and 71 patients who had undergone radical mastectomy (RM group) revealed that 85% and 73%, respectively, were satisfied with their operative results. BCT appeared superior to RM in relation to body image, with 93% of the BCT group indicating BCT as a future choice of treatment, whereas only 35% of the RM group indicated RM as a future choice of treatment. For 59% of the BCT patients, the results were considered excellent or good by a physician, but fear of recurrence was frequently expressed by both groups even though an early stage of breast cancer had been significantly more common in the BCT group than the RM group. Sexual adjustment was the same in both groups. Body image was thus concluded to have been improved by BCT rather than RM, but psychological morbidity was essentially the same in both groups. PMID- 8369612 TI - A new animal model for split liver transplantation using an infrahepatic IVC graft. AB - An animal model of split liver transplantation using pigs is described herein. The donor liver was divided into two grafts, the right graft consisting of the right medial and lateral segments with the caudate lobe, and the left graft consisting of the left lateral and medial segments. To make implantation easier, a distal part of the donor's inferior vena cava (IVC) was isolated and attached to the left graft with an anastomosis between the orifice of the renal vein and the graft's hepatic vein. The left graft thereby contained a newly constructed retrohepatic IVC for anastomosis to the recipient. During the anhepatic phase, no conventional bypass procedure was used, but an abdominal aortic clamp in combination with general hypothermia was employed. Ten pigs were used as donors and a total 20 liver transplantations performed. No immunosuppressive drugs were given in this series. Ten of the 20 recipients survived for more than 2 days, the mean survival time being 4.7 days, with a range of 2-14 days. The mean survival time of the left grafts was much longer than that of the right grafts, although no technical problems such as kinking of the graft or occlusion of the hepatic vein were encountered in either. This model is the first report of split liver transplantation in animals. The advantages of using the infrahepatic IVC graft include stability of the graft and safe hepatectomy. This model will therefore be useful for the experimental study of split liver transplantation and may also be employed for clinical use in the future. PMID- 8369613 TI - The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo. AB - We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40-80 micrograms/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m2, this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas. PMID- 8369615 TI - Thymic metastasis from prostatic carcinoma: report of a case. AB - The thymus is an important organ involved in cell-mediated immunological function, and to our knowledge, there has never been a case of thymic metastasis reported. We recently examined a 65-year-old man who presented at our department with a cough and shortness of breath on exertion. He had a history of prostatic carcinoma for which he had undergone an orchiectomy 11 years previously. Investigations disclosed a mediastinal tumor, 14 x 9 cm in size, and histological examination of the resected tumor confirmed a diagnosis of thymic metastasis from prostatic carcinoma. PMID- 8369614 TI - The effects of a biological response modifier, OK-432, on tumor-induced alterations in the host metabolism. AB - The effects of multicytokine inducer, OK-432, on tumor-induced metabolic alterations were studied by assessing three key regulatory enzymes of gluconeogenesis, de novo fatty acid synthesis and the triglyceride clearance pathways. Two Klinish Einheit (KE) of OK-432 was subcutaneously injected on alternate days, for 10 days, into Fischer 344 rats with or without methylcholanthrene-induced sarcoma. At the time of sacrifice, the tumors accounted for approximately 23% of their total body weight. The injections of OK 432 did not affect the amount of food intake in either the tumor bearers or the controls. The tissue lipoprotein lipase activities in the epididymal fat pads of the tumor bearers were significantly decreased compared with the controls (P < 0.01). Phosphoenolpyruvate carboxykinase activity in the liver was significantly increased (P < 0.01), while malic enzyme activity tended to be decreased in the tumor bearers compared with the controls. However, there were no significant differences in those activities depending on the OK-432 injections, even though OK-432 induced tumor necrosis factor (TNF) and increased cytotoxic activities in the mesenteric lymph nodes as well as in the spleen. Thus, although the role of monokines in inducing cancer cachexia is not yet clearly understood, OK-432 was not able to revert the tumor-induced metabolic alterations which lead to tissue wasting and cancer cachexia. PMID- 8369616 TI - Lumbar artery pseudoaneurysm: an unusual cause of a retroperitoneal hematoma: report of a case. AB - Pseudoaneurysm of the lumbar artery is a rare complication of penetrating trauma. We present herein a case thought to have been caused by a blow to the left flank without any evidence of a stab wound. In this patient, the diagnosis of a first lumbar artery pseudoaneurysm with a retroperitoneal hematoma was confirmed by computed tomography (CT) findings, after which transcatheter embolization was successfully performed. PMID- 8369617 TI - The neurosurgical management of brain metastasis from colorectal cancer: a report of three cases. AB - We report herein three cases of brain metastasis from primary colorectal cancer in which the metastatic lesion was resected to effectively relieve neurological symptoms. Case 1 was a 61-year-old woman with a solitary brain metastasis from colorectal cancer and no other metastases; case 2 was a 59-year-old woman who died from liver metastasis 11 months after resection of the metastatic brain tumor; and case 3 was a 68-year-old woman with multiple metastases to the lungs and bones detected before the brain metastasis. According to 16 cases previously reported in the Japanese literature and our 3 cases, the interval between diagnosis of the primary cancer and discovery of brain metastasis was 23 months on average, while the median survival after the discovery of brain metastasis was 7 months. Brain metastases with liver and lung metastases were seen more frequently than brain metastases alone. In these three cases, chemotherapy appears to have been of no use in preventing recurrence. Thus, we believe neurosurgical management to be appropriate for a solitary lesion and that it should be actively pursued to prolong survival and improve quality of life. PMID- 8369618 TI - Hemangiopericytomatous meningioma metastasized to the liver: report of a case and review of the literature. AB - A 54-year-old male was admitted to our hospital for treatment of a liver tumor which was pointed out by screening ultrasonography. Computed tomography revealed a tumor in the right lobe of the liver measuring 7 cm in diameter. Angiography revealed a hypervascular tumor. A hepatocellular carcinoma or hypervascular metastatic tumor was suspected. A right hepatic lobectomy was performed. The patient had previously undergone operations for a hemangiopericytomatous meningioma in the occipital fossa in 1972 and 1977. The histological findings of the liver tumor were identical to those for hemangiopericytomatous meningioma, so the etiology was considered to be liver metastasis from the previous meningioma. Nineteen cases of extracranial metastasis of hemangiopericytomatous meningioma have been reported in the literature, but hepatic resections of this metastasizing tumor have been very rare. PMID- 8369619 TI - Extended right lobectomy for Caroli's disease: report of a case and review of hepatectomized cases in Japan. AB - A 27-year-old man was admitted to Nagasaki University Hospital complaining of fever. Percutaneous transhepatic cholangiography revealed multiple cystic dilatations of the intrahepatic bile ducts of the right lobe, as well as three obvious cystic dilatations and several small dilatations of the intrahepatic bile ducts of the left lobe. An extended right lobectomy was performed. However, the patient later suffered from repeated cholangitis and required the administration of antibiotics as a result of remnant cystic dilatations and stricture of the extrahepatic bile duct following hepatectomy. A slight enlargement of the remnant cystic dilatations, but no new cystic dilatations, were also recognized in the regenerating liver. We reviewed nine cases of hepatectomy for Caroli's disease reported in the Japanese literature, as well as our own case. Among these, four of the seven patients subjected to hepatic resection involving unilateral lobe demonstrated a good recovery. On the other hand, it is difficult to successfully treat Caroli's disease involving both lobes of the liver by hepatic resection. PMID- 8369620 TI - Curricular changes and improved performance by high-risk students on the National Boards Part I. AB - The present study was undertaken to identify the components of an introduction to clinical medicine (ICM) course at Morehouse School of Medicine that were most helpful in improving performance on the National Board of Medical Examiners (NBME) part I examination by an academically high-risk population. After completing a revised ICM course that incorporated problem-based learning-style innovations, students performed significantly better on the NBME part I. The students did not differ from their predecessors demographically or academically. A modified Likert scale questionnaire revealed subjects' agreement with the helpfulness of each ICM component. Open-ended questions elicited other helpful factors. Case-based learning, small discussion groups, quiz discussions, immediate quiz feedback, basic scientist involvement, and faculty role models were found most helpful. Non-ICM-related factors of value included support of family and friends and diligent studying. PMID- 8369621 TI - Interstitial cystitis in minority women. AB - A bladder disorder of unknown etiology, interstitial cystitis affects mainly women, and its prevalence may be increasing. Little information is available on the demographic, clinical, diagnostic, and treatment aspects of interstitial cystitis in the minority population. This retrospective review of the patient database at the Interstitial Cystitis Center, New England Medical Center, identified 17 minority women among a total of 201 patients who satisfied the criteria of the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases for diagnosis of interstitial cystitis. Minority women accounted for 8.5% of the patients, with 3% being African American; 3.5%, Hispanic American; and 2.0%, Asian American. The clinical and endoscopic findings as well as responses to treatment were similar in both the minority and nonminority populations. However, the average duration of symptoms prior to diagnosis was 2.9 years in the minority group, compared with an average of 13 months in the nonminority group. Minority women with interstitial cystitis appear to be symptomatic for longer periods before a definitive diagnosis is made. Their response to treatment parallels that of the nonminority population. Further studies are needed to address the natural history, urologic referral patterns, and treatment outcomes in minority women who have interstitial cystitis. PMID- 8369622 TI - The history of African-American physicians and medicine in the United States. PMID- 8369623 TI - Recent advances in the understanding of potassium channel function. PMID- 8369624 TI - Structure of nicotinic acetylcholine receptors. AB - Nicotinic acetylcholine (ACh) receptors convert the binding of ACh into the opening of a cation-conducting channel. New information about the regions of the receptor most immediately involved in its function, namely the ACh-binding sites, the gate and the channel, has come from two approaches. One is the identification by labelling and by mutagenesis of residues contributing to these regions. Another is the determination of the three-dimensional structure of the receptor by electron microscopy. Although the identification of functionally relevant residues is incomplete and residues cannot yet be resolved in the three dimensional structure, the two approaches are converging. There is still room in the gap for speculation. PMID- 8369625 TI - A new wave of serotonin receptors. AB - The neurotransmitter serotonin mediates diverse effects through multiple receptor subtypes. Recently, many of these receptor subtypes have been identified, molecularly cloned and characterized, advancing our understanding of their functional roles in the central and peripheral nervous systems. PMID- 8369626 TI - Synaptic vesicle proteins in exocytosis: what do we know? AB - Synaptic release of neurotransmitters is a fast process that is mediated by Ca(2+)-dependent exocytosis of synaptic vesicles. Several abundant membrane proteins of synaptic vesicles have been characterized at the molecular level but their function in synaptic vesicle traffic is poorly understood. Recent evidence suggests that some of these proteins are involved in exocytotic membrane fusion. PMID- 8369627 TI - Signal recognition and integration by Gs-stimulated adenylyl cyclases. AB - Six Gs-stimulated adenylyl cyclases have been cloned. Two additional forms have been identified as partial cDNAs. These adenylyl cyclases have distinct functional properties and are differentially regulated by protein kinases. The adenylyl cyclases have distinct patterns of distribution in peripheral tissues and various brain regions. The unique functional characteristics of the members of this effector family may allow each cell type and/or brain region to customize the signal-recognition and integrative properties of its cAMP-generation system by varying the ratios of the various adenylyl cyclases. PMID- 8369628 TI - Pleiotropic signaling from receptor tyrosine kinases. AB - The molecular cloning of genes encoding new neuroactive growth factors and their receptors has greatly enhanced our understanding of important interactions between receptors and signaling molecules. These studies have begun to illuminate some of the mechanisms that allow for specificity in neuronal signaling. PMID- 8369629 TI - Novel inositol containing phospholipids and phosphates: their synthesis and possible new roles in cellular signalling. AB - Details of the widely employed PtdIns(4,5)P2 hydrolysis receptor-stimulated signalling pathway continue to be elucidated rapidly. However, it has recently become apparent that numerous other inositol lipids and phosphates are widespread and are likely to have important cellular functions. In this review, we focus particularly on three rapidly progressing areas: the synthesis and possible functions of 3-phosphorylated inositol lipids, particularly phosphatidylinositol 3,4,5-trisphosphate; the roles of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in coordinating intracellular Ca2+ mobilization and Ca2+ influx in stimulated cells; and the metabolism and possible functions of other inositol polyphosphates and of inositol polyphosphate pyrophosphates. PMID- 8369630 TI - Cellular mechanisms of long-term depression in the cerebellum. AB - Cerebellar long-term depression is a persistent, input-specific attenuation of the parallel fiber-Purkinje neuron synapse induced by co-activation of parallel fibers and climbing fibers. This phenomenon endows the Purkinje neuron with a powerful associative computational ability. Recent investigations have provided strong evidence that two mechanisms, Ca2+ influx via voltage-gated channels, and stimulation of protein kinase C via metabotropic receptor activation, are required for induction of long-term depression. In addition, two other mechanisms, Na+ influx via AMPA receptors, and stimulation of a nitric oxide/cGMP cascade may also be involved in this process. PMID- 8369631 TI - Signalling mechanisms. PMID- 8369632 TI - A connectionist approach to the prefrontal cortex. AB - Recent data from studies of the prefrontal cortex (PFC) in humans and laboratory animals are reviewed with particular reference to the anatomical substrates of prefrontal neuropsychological function in health and disease. The PFC has been shown to have a unique pattern of supramodal connectivity with intracortical and subcortical circuits that place the PFC in an anatomical position to subserve "executive" cognitive functions and modulate limbic information to relate to basal ganglia circuits in a highly specific manner and to uniquely control the neurochemical elements of attention and reward. PFC connectivity is also consistent with current hypotheses about prefrontal neuropsychology, which emphasize conscious, goal-directed behavior guided by past experience. PFC connectivity explains the frequency with which prefrontal dysfunction is seen in disease states, which, on the basis of neuroimaging and neuropathology data, can be categorized as either intrinsic or dysconnection disorders. PMID- 8369634 TI - Regional syndromes. PMID- 8369633 TI - Drug and alcohol use and neuropsychological performance in asymptomatic HIV infection. AB - The effect of drug and alcohol abuse on neuropsychological performance was examined in 132 human immunodeficiency virus-seropositive gay or bisexual men. Syndromal (diagnostic) criteria of alcohol/drug abuse based on DSM-III-R were used, and quantitative estimates of alcohol consumption were obtained. Very few differences appeared between substance abuse subgroups formed on the basis of recency or severity of drug use. There were some correlations with the quantitative estimate of alcohol use, but not on the measures previously found to differentiate seronegative and asymptomatic seropositive gay men. These data indicate that alcohol use does affect neuropsychological performance but does not account for the differences observed in studies of seronegative and seropositive subjects. PMID- 8369635 TI - Dementia. PMID- 8369636 TI - Similarities and differences in memory deficits in patients with primary dementia and depression-related cognitive dysfunction. AB - The authors examined differences between the verbal memory performance of older patients with major depression (MD) alone; major depression with reversible depression-related cognitive dysfunction (MD/DRCD); and primary dementia and major depression (DEM/MD). Patients were evaluated before antidepressant treatment and 6 and 15 months after treatment. Of the three groups, patients with MD alone acquired significantly more information on the California Verbal Learning Test and showed a more pronounced primacy effect. Patients with DEM/MD were more likely to commit errors of intrusion. Although older depressed patients with MD/DRCD may resemble patients with DEM/MD on some aspects of verbal memory performance, differences may be observed in the types of learning errors they commit. Diagnostic implications are discussed. PMID- 8369637 TI - Relationship of seizure variables to personality disorders in epilepsy. AB - Among epileptic patients, personality disorders may be associated with specific seizure manifestations. In an epilepsy clinic, we identified 42 idiopathic epilepsy patients diagnosed with various DSM-III-R personality disorders, including borderline, atypical or mixed, explosive, and dependent. When compared with 42 age- and sex-matched epileptic control subjects on six seizure variables, the personality disorder group had more patients with epileptic auras (P = 0.001), particularly "cephalic" auras, and fewer with secondarily generalized tonic-clonic seizures (P < 0.05). These findings suggest that the experience of epileptic auras contributes to the development of personality disorders, especially when auras are not masked by secondarily generalized seizures. PMID- 8369638 TI - Midline cerebral malformations and schizophrenia. AB - To investigate a possible association of midline cerebral malformations with psychotic disorders, MRI and CT scans were blindly evaluated for 52 patients with schizophrenia, 9 with schizoaffective disease, and 79 consecutive nonpsychotic control subjects. Midline abnormalities were present in 10 of 61 patients (16.4%) versus 4 of 79 control subjects (5.1%; P < 0.05, chi-square). Of 52 schizophrenic patients, 8 had abnormalities of the septum pellucidum (SP): 5 had cavum vergae (CaV), 2 had cavum septum pellucidum (CaSP), and 1 had agenesis of the corpus callosum and SP. Of 9 schizoaffective patients, 2 had SP abnormalities: 1 CaV and 1 CaSP. Abnormalities of the SP, especially CaV, were significantly more frequent in women than in men (P < 0.02, chi-square). PMID- 8369639 TI - Patterns of neuropsychological deficits that discriminate schizophrenic individuals from siblings and control subjects. AB - Previous research on persons with schizophrenia and their relatives suggests two independent etiologic factors may combine to produce schizophrenia, and these factors may be indexed respectively by independent neuropsychological tests. Two neurocognitive measures, the Trail Making and Wisconsin Card Sorting (WCST) tests, were administered to 28 schizophrenic subjects, 15 nonschizophrenic siblings, and 35 control subjects by investigators blind to DSM-III-R diagnoses. Results support key predictions of a two-factor model: 1) having poor scores on both tests discriminated schizophrenic individuals from both siblings and control subjects, and 2) poor Trail Making and WCST performance were inversely associated among schizophrenic individuals' non-schizophrenic siblings. PMID- 8369640 TI - Early childhood abuse and limbic system ratings in adult psychiatric outpatients. AB - The authors investigated the hypothesis that early abuse might affect the development of the limbic system. During initial psychiatric evaluation, 253 outpatients completed a self-report scale, the Limbic System Checklist-33 (LSCL 33), designed to measure somatic, sensory, behavioral, and memory symptoms suggestive of temporal lobe epilepsy, along with a questionnaire about physical or sexual abuse. Physical abuse was associated with a 38% increase in LSCL-33 scores (P < 0.01), sexual abuse with a 49% increase (P < 0.02), and combined abuse with a 113% increase (P < 0.0001). Physical or sexual abuse alone was associated with elevated LSCL-33 scores only if the abuse occurred before age 18. PMID- 8369641 TI - Clinical and neurochemical effects of fenfluramine in children with autism. AB - Fifteen children with autism were treated with 60 mg d,l-fenfluramine (FEN) or placebo in a double-blind A-B-A protocol followed immediately by double-blind placebo-controlled crossover administration of FEN (total duration 62 weeks). Both biochemical and clinical outcomes were examined. Biochemically, FEN led to an increase in dihydroxyphenylacetic acid (DOPAC) and decreases in whole-blood serotonin (5-HT), plasma norepinephrine (NE), and plasma 3-methoxy-4 hydroxyphenylglycol (MHPG). The decrease in whole-blood 5-HT was seen only during treatment with FEN. However, NE levels did not return to baseline as long as 8 weeks after the first FEN treatment period. Increases in DOPAC were greater during the second FEN treatment period than the first. Persistent changes in catecholamine regulation may be related to previously reported long-term effects on central nervous system 5-HT after FEN. Clinically, FEN led to a modest decrease in parent, but not teacher, ratings of hyperactivity and to a small reduction in sensorimotor abnormalities. Abnormal social and affectual responses also decreased, but this was not directly related to FEN treatment. Effects on cognition were equivocal. Hyperserotonemic subjects did not differ from normoserotonemic subjects in clinical response. Overall, no significant advantage for the use of FEN could be established. PMID- 8369642 TI - EEG coherence in men with AIDS: association with subcortical metabolic activity. AB - The authors studied the relationship between cerebral metabolism and brain electrical activity in patients with acquired immunodeficiency syndrome (AIDS), using positron-emission tomography and quantitative electroencephalography. Electroencephalographic coherence in the 6-to 10-Hz band correlated positively with thalamic metabolic activity. Coherence adjusted for background activity correlated strongly and positively with basal ganglia metabolic activity. Posterior interhemispheric coherence showed the highest correlations with measures of metabolic activity. These results suggest that changes in coherence may reflect AIDS-related subcortical disease. The high correlations between the two different measures of cerebral activity support the validity of electroencephalographic coherence measures in studies of AIDS-related neuropsychiatric dysfunction. PMID- 8369643 TI - Human brain fluoxetine concentrations. AB - Data on 22 subjects treated with fluoxetine suggest that magnetic resonance spectroscopy (MRS) of fluorine-19 can measure brain concentrations of fluoxetine/norfluoxetine in vivo. Fluoxetine accumulates in the human brain relative to plasma, with brain concentrations of fluoxetine/norfluoxetine ranging up to 10.7 micrograms/ml. Brain concentrations may reach a plateau between 6 and 8 months of treatment. The apparent concentration in brain relative to plasma is 20:1, roughly parallel to brain antidepressant concentration ratios in animal studies. PMID- 8369644 TI - Separation of affective disorder into seasonal and nonseasonal types using motion sickness susceptibility as a marker. AB - A sample of 133 candidates for antidepressant or mood-stabilizing medication treatment, with acute onset or a new phase of illness between the autumnal and vernal equinoxes, was gathered over a 3-year period from a private outpatient practice. All patients were diagnosed using DSM-III-R criteria, rated on a standard motion sickness (MS) questionnaire, and asked whether they had experienced cardinal symptoms of seasonal affective disorder (SAD). There was a positive relationship between greater MS and SAD in the entire patient sample. When a subsample of 23 patients was given a 2-week trial of phototherapy and rated for improvement, MS-susceptible patients responded better than MS-resistant patients. PMID- 8369645 TI - Cerebrospinal fluid thyrotropin-releasing hormone concentrations in patients with anxiety disorders. AB - In a study of 45 patients with anxiety disorders and 11 control subjects, mean cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone (TRH) were not significantly different between nonpsychiatric control subjects and those with panic disorder, generalized anxiety disorder, or obsessive-compulsive disorder. Male subjects, regardless of diagnosis, had significantly higher mean CSF concentrations of TRH than females. PMID- 8369646 TI - In vivo quantitation of basal ganglia and thalamic degenerative changes in two temporal lobectomy patients with affective disorder. AB - The authors examined the brain magnetic resonance imaging scans of two epilepsy patients who had temporal lobectomies, one on the right and one on the left, with postoperative symptoms of affective disorders. Degenerative changes of ipsilateral thalamus and putamen after surgery, with coincident affective disorder, were noted. The authors discuss a possible relationship between postlobectomy degeneration and depression. PMID- 8369647 TI - Automobile driving fitness and neurological impairment. PMID- 8369648 TI - Thyrotropin-releasing hormone in a patient with bipolar disorder. PMID- 8369650 TI - Two simple methods for measuring iodine in urine. AB - Urinary iodine excretion is currently the most convenient laboratory marker of iodine deficiency. Accelerating international interest in correcting this condition demands rapid, simple methods for assessment and monitoring. We describe two adaptations of the Sandell-Kolthoff reaction, in which urine is first digested with chloric acid and iodine then determined from its catalytic reduction of ceric ammonium sulfate in the presence of arsenious acid. Both methods use gentle digestion by chloric acid in a heating block. Method A detects iodine in a colorimeter, method B by the indicator ferroin and a stopwatch. Results with 12 samples ranging from 1.8 to 19.0 micrograms/dL (0.14-1.48 mumol/L) differed from those in a reference laboratory by a mean of 9.1% for method A and 15.7% for method B. One technician can perform at least 150 tests per day at a total cost of less than $0.50 each. The speed, low cost, and simple instrumentation make these methods well suited to epidemiological assessment of iodine deficiency in developing countries. PMID- 8369649 TI - The measurement of fecal thyroxine in the diagnosis of thyrotoxicosis factitia. AB - Two patients with prolonged thyrotoxicosis are presented with low radioiodide uptake, low-normal serum thyroglobulin concentrations, and low iodide content of the neck on x-ray fluorescence studies. The surreptitious intake of thyroid hormone was directly proven by a high fecal concentration of T4 (12.38 and 23.99 nmol/g) compared with low concentrations in healthy subjects (1.03 +/- 0.64 nmol/g; mean +/- SD, n = 6) and in patients with hyperthyroidism due to Graves' disease (1.93 +/- 1.86; n = 8). Fecal thyroid hormone measurement may help to provide formal proof of factitious thyrotoxicosis. PMID- 8369651 TI - Hashimoto's thyroiditis in association with Tolosa Hunt syndrome: a case report. AB - Tolosa Hunt syndrome (THS) is a painful ophthalmoplegia due to a nonspecific inflammatory process in the cavernous sinus or to parasellar neoplasms. Although the cause of the disease is unknown, previous observations support the hypothesis that THS may be only one manifestation of a generalized vasculitis. The diagnosis is based on findings of painful ophthalmoplegia, excellent response to corticosteroids, and exclusion of other causes including aneurysm, diabetes mellitus, paranasal mucocele, and carotid cavernous fistula. We report the case of a 24-year-old woman with THS who had undergone thyroidectomy 4 years before admission for goiter with histologic diagnosis of Hashimoto's thyroiditis. This case shows the unusual association between Hashimoto's thyroiditis and THS and supports the autoimmune origin of both diseases. PMID- 8369652 TI - Glucose transport stimulation by thyroid hormone in ARL 15 cells: partial role of increased GLUT1 glucose transporter gene transcription. AB - We have previously reported that the stimulation of glucose transport by thyroid hormone in the rat liver-derived ARL 15 cell line is attributable, at least in part, to increased abundance of cellular glucose transporters with a corresponding increase in the mRNA coding for the GLUT1 glucose transporter isoform. To elucidate further the mechanism by which thyroid hormone increases glucose transport, we examined the time-course of the effect of L triiodothyronine (T3) on 3H-2-deoxyglucose uptake, GLUT1 protein abundance, and GLUT1 mRNA abundance in ARL 15 cells. At 6 h of T3 treatment, 3H-2-deoxyglucose uptake was increased by 40 +/- 11%, whereas the abundance of GLUT1 protein in cell extracts had not yet changed at this time. At 48 h, GLUT1 protein was increased by 58 +/- 10%, whereas 3H-2-deoxyglucose uptake at this time was increased by 116 +/- 14%. GLUT1 mRNA levels rose within 4 h of T3 treatment, preceding the increase in GLUT1 protein, and more than doubled by 24 h. In additional experiments to determine the mechanism by which T3 increases GLUT1 mRNA, T3 treatment for 48 h increased the rate of transcription of the GLUT1 gene, determined by nuclear run-on analysis, by 55 +/- 11%. T3 treatment did not significantly alter the half-life of GLUT1 mRNA. In the presence of inhibitors of protein synthesis, GLUT1 mRNA increased at 6 h (5-7-fold), but there was no further induction of this mRNA by T3 in the presence of these inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369653 TI - Defective organification of iodide causing hereditary goitrous hypothyroidism. AB - We present a survey of the current state of knowledge about the prevalence of the syndrome involved in defective organification of iodide, and the mechanism of iodination and coupling catalyzed by the thyroid peroxidase (TPO) enzyme. A brief summary of the recent developments in molecular cloning of TPO and regulation of TPO gene expression is also included. Methods for purification of the enzyme and details about the assessment of TPO activity in tissue are briefly explained. The classification of defective organification of iodide is primarily based on the site of the biochemical defect, being quantitative (TPO absent) or qualitative (TPO structure, localization or apoenzyme are defectives). The presence of TPO inhibitors is also briefly described. The rare possibility of an absent source of peroxide (H2O2) causing defective iodide organification is discussed. Analysis of the 118 reported cases shows that the biochemical classification covers a spectrum of abnormalities and it is likely that further molecular biology studies will increase this heterogeneity as well as refining it. Genetic studies have suggested linkage between the TPO gene polymorphisms and the iodide organification defect and can be of importance for carrier detection and prenatal diagnosis. Neonatal screening for hypothyroidism is likely to expand the number of cases available for DNA analysis and possibly the molecular diagnosis. The importance of the mutations that would affect the histidine (His) residues in the translated protein was recently documented by the finding of a deletion removing part of exon 9 and thus also deleting a proximal His residue. The resulting TPO enzyme was inactive for iodide organification and coupling reaction. It is hoped that in time we will be able to expand our knowledge of the molecular diagnosis of the inborn errors of iodide organification. PMID- 8369655 TI - Classification of Graves' ophthalmopathy. PMID- 8369654 TI - The finding of 3'-3,5 triiodothyronine: personal account. PMID- 8369656 TI - Thyroid hormone levels affected by time of blood sampling in thyroxine-treated patients. AB - Patients receiving exogenous levothyroxine are reported to have higher total and free serum thyroxine levels than euthyroid controls. This may be an artifact of the serum collection time. We explored the effect of collection time on serum levels of thyroid hormones in outpatients receiving levothyroxine for replacement therapy (26 patients) or suppression of thyrotropin (25 patients). Blood samples, obtained during regular clinic visits (random samples) and at more than 22 h from ingestion of levothyroxine (trough samples), were assayed for total and free thyroxine, triiodothyronine, and thyrotropin. Four athyreotic patients on levothyroxine therapy had serial blood sampling over 24 h. Compared to corresponding trough samples, random samples had elevated total thyroxine levels in patients receiving replacement (8.1 +/- 1.2%, mean +/- SE, p = 0.0001) and in patients undergoing suppression (8.8 +/- 1.6%, p = 0.0001). Free thyroxine was increased by 12.7 +/- 2.6% (p = 0.0003) and 14.5 +/- 2.3% (p = 0.0001), respectively, compared with trough samples. Thyrotropin levels were 18.9 +/- 6.8% (p = 0.003) lower in patients receiving replacement and triiodothyronine levels showed small or no changes. Time-course analysis showed that free and total thyroxine levels remained significantly elevated above baseline for 9 and 5 h, respectively, after a levothyroxine dose. In conclusion, there is a transient increase in thyroid hormone levels for 9 h after an oral levothyroxine dose. Accurate assessment of thyroid hormone levels in patients receiving levothyroxine therapy should take this into account. This has greatest significance in selecting minimal levothyroxine dosages for suppression of thyrotropin. PMID- 8369657 TI - Surgery for solitary thyroid nodules: assessment of methods to select patients at low risk for unsuspected malignancy in the unaffected lobe and the possible utility of preoperative thyroid ultrasound. AB - One hundred and twelve bilateral thyroidectomies for solitary thyroid nodules with suspected malignancy were performed. The incidence of malignancy in the 112 primary nodules was 42%. Twenty-nine of the 112 contralateral lobes (26%) contained malignancy, which was unsuspected in 80%. Of these 29, 20 were foci of papillary cancer < or = 5 mm and 9 were larger papillary tumors or follicular carcinoma. We analyzed these 112 patients to determine whether there was a simple method to identify those patients at risk for contralateral, unsuspected malignancy. With use of the AMES clinical staging retrospectively, 70 of the 112 patients were classified as having low-stage disease. Fifty percent (35) had cancers on the primary side and 27% (19) on the contralateral side. Of these 19 contralateral cancers, 14 were papillary cancers < or = 5 mm, 4 were papillary cancer > 5 mm and one was a 1.5 cm follicular carcinoma, a similar distribution as in the whole group of 112. When the AMES analysis then excluded those thought to be at risk for multicentricity or papillary carcinoma and examined female patients only with nonpapillary frozen sections, nonpapillary aspiration cytological results, and no history of radiation exposure, no further reduction in the proportion of contralateral cancers (7 of 26, 27%) was found. Fifty-five of the 112 patients underwent preoperative ultrasound scans. In those cases in whom the contralateral lobe had no intraoperative palpable or preoperative sonographic mass, 5 of 20 still had contralateral cancers, but all were papillary < or = 5 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369658 TI - Clinical aspects of primary thyroid lymphoma: diagnosis and treatment based on our experience of 119 cases. AB - We describe the clinical aspects of primary thyroid lymphoma, particularly diagnostic procedures and successful therapy based on our observation of 119 patients with primary thyroid lymphoma. Thyroid lymphoma occurred exclusively in the thyroid gland of patients with Hashimoto's thyroiditis as a rapidly growing mass in the thyroid gland. Therefore, progressively enlarging goiter and compression symptoms were the most common clinical manifestations. A significant number of patients in our series had subclinical hypothyroidism (14%) or overt hypothyroidism (27%) because of the coexistence of Hashimoto's thyroiditis. Whenever thyroid lymphoma is suspected, we recommend an ultrasound scan of the thyroid gland and fine needle aspiration biopsy as initial diagnostic procedures. Thyroid ultrasound showed characteristic asymmetrical pseudocystic pattern in 43 of the 46 patients (93%), and thyroid cytologic examination showed abundant monomorphic infiltration of lymphoid cells. Among 83 patients who underwent fine needle aspiration biopsy, 65 patients (78.3%) were diagnosed correctly and 10 patients (12%) had borderline cytologic results. Thus, 90% of patients with thyroid lymphoma were diagnosed or the diagnosis suspected based on fine needle aspiration biopsy. To confirm the diagnosis of lymphoma histologically and to determine the degree of malignancy, open biopsy taking 2-3 g tissue should be done for all cases. Treatment of thyroid lymphoma does not require resection of all lymphoma tissue or total thyroidectomy. Our successful treatment is radiation therapy combined with six courses of CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisolone). This mode of therapy improved the 8-year survival rate to nearly 100% regardless of the histological type of malignancy. PMID- 8369659 TI - Platelet volume: laboratory measurement and clinical application. AB - Modern cell analyzers routinely produce platelet indices, but many clinicians do not utilize them in clinical decision-making. In part this can be attributed to difficulties with their laboratory measurement. The mean platelet volume is dependent on a number of variables, including time of analysis after venepuncture, method of analysis, anticoagulant used and specimen storage temperature. The influence of these laboratory variables is significant and reproducible mean platelet volumes are dependent on standardized laboratory methodology. When pre-analysis factors are controlled, alterations in platelet volume can be demonstrated in a number of disease states and assessment of platelet volume can be useful in the monitoring and diagnosis of patients. An understanding of the pathophysiology of alterations in platelet volume and of the inverse relationship between platelet volume and count is a prerequisite for the successful clinical application of platelet volume measurements. PMID- 8369660 TI - Management of the hematologic manifestations of HIV disease. PMID- 8369661 TI - Fluorescence in situ hybridization. AB - Spectacular advances in the use of fluorescence in situ hybridization (FISH) for the visualisation of specific DNA sequences in metaphase chromosomes and interphase cells have been made over the last few years making the technique a useful tool in clinical research. One of the biggest impacts has been in the field of detection and diagnosis of human malignancies. Chromosomal translocations, deletions, amplification of specific genes and changes in chromosome number can all be detected in the non-dividing interphase nucleus using probes ranging from whole chromosome 'paints' to individual gene specific probes. Gene mapping has also benefited from advances in FISH technology. Target sequences ranging from one to several hundred kilobases can be visualised on metaphase chromosomes and spatial resolution in interphase cells permits the ordering of two probes over a distance as small as 1000 base pairs. The potential uses of FISH continue to increase with each new technical innovation. PMID- 8369662 TI - Membrane proteins in paroxysmal nocturnal haemoglobinuria. AB - A review of recent information on the abnormalities of the blood cell membrane in paroxysmal nocturnal haemoglobinuria (PNH) is presented, with a detailed analysis of biochemical and flow cytometry findings. The complex patterns observed in the various cell lineages of which the PNH clone consists are described, and a simplified monoclonal antibody panel is defined for diagnostic purposes. Available data on in vitro culture of progenitor cells and on the recent establishment of PNH cell lines are summarized. Finally, we discuss speculative hypotheses on the growth advantage of the PNH clone. PMID- 8369663 TI - The changing course of thrombotic thrombocytopenic purpura and modern therapy. AB - Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder of unknown etiology. Pathologically, there appears to be an abnormal interaction between the vascular endothelium and platelets, but the primary event remains uncertain. While historically, TTP was a fatal disease, dramatic improvement in its outcome has occurred over the past two decades with the development of effective therapy. Plasma infusion or exchange remains the cornerstone of the treatment of TTP, along with corticosteroids, platelet inhibitor drugs, vincristine and splenectomy. This review summarizes the clinical findings, what is known of the pathogenesis and the available therapeutic modalities for TTP. In most cases, remissions can be attained and cures are now common. However, approximately half the patients will relapse. The clinical course at relapse is usually milder than the disease at presentation and less aggressive therapy may be needed. However, relapsing TTP still carries a significant mortality and preventive therapies are not always effective. Further progress may have to await an understanding of the fundamental etiology of this disease. PMID- 8369664 TI - A health care revolution. PMID- 8369665 TI - Nurse practitioners: primary providers at Lehigh County Visiting Nurse Association Family Health Clinic. PMID- 8369666 TI - Legal issues relating to access to medical records. PMID- 8369667 TI - Nurse-managed health care: an ongoing tradition. AB - Nurse-managed health care is a concept that has received much attention lately; however, it is not a new idea. Nurse-managed health care has been delivered through nursing centers since the beginning of the 20th century. This article examines the history of nursing centers and reports on the current diversity that exists in these centers today. Characteristics of academic and nonacademic nursing centers are examined through a review of the few studies currently available in the literature. PMID- 8369668 TI - Establishing a nurse-managed health center: getting started. AB - Many nurses are deciding that the best way to meet health care needs of clients and ensure high quality care is to establish a nurse-managed health center. This article provides practical information on assessing the need for such a center, determining the scope of services to be provided, obtaining the financial resources needed, and determining the staff and facilities required. The application of this information can make the center a reality. PMID- 8369669 TI - Establishing a nurse-managed health center: interacting with regulatory, professional, and fiscal environments. AB - In establishing a nurse-managed health center, one must be cognizant of legal and regulatory issues that could impact on the practice. The ability to negotiate outside services, such as laboratory and medical consultation, is important. Additionally, as an integral component of financial viability, attainment of third-party reimbursement should be considered. PMID- 8369670 TI - Establishing a nurse-managed health center: assuring excellence. AB - The roles of accreditation, clinical protocols, and quality assurance in maintaining high standards of quality in the nurse-managed health center are discussed. The components of a quality assurance program for the nurse-managed center are presented, including peer chart review, diagnosis-related review, and review of high-risk client encounters. Various methods of generating practice protocols for the nurse-managed center are outlined. PMID- 8369671 TI - The solo nurse practitioner: a private practice model. AB - This article discusses the experience of one NP through 4 years of an independent private practice. Suggestions are offered for those considering the option. Personal, practical, and financial factors should be carefully considered. Business training and a business plan are essential. Expected and unexpected outcomes are shared with the reader. PMID- 8369672 TI - Establishing a nurse-managed center: a community approach. AB - Documentation of need, designing and implementing services to meet the need, networking with and referral to other community providers, practice agreements, and mechanisms for reimbursement and billing are just a few issues that must be addressed when establishing a community-based health care unit. This article will discuss essentials of establishing a nurse-managed, community-based health care center, based on the author's experience in developing and managing the Outreach Health Care Unit. PMID- 8369673 TI - Combating blinding trachoma. PMID- 8369674 TI - Reflex anoxic seizures. PMID- 8369675 TI - Who needs dual chamber pacing? PMID- 8369676 TI - Doctors and markets. PMID- 8369677 TI - The new information management and technology strategy of the NHS. PMID- 8369678 TI - Wanted: guidelines that doctors will follow. PMID- 8369679 TI - France's Court of Appeal sentences blood officials. PMID- 8369680 TI - Squabbles over AIDS vaccine trials nearly over. PMID- 8369681 TI - Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study. AB - OBJECTIVE: To study outcome after lengthy febrile convulsions and status epilepticus in children. DESIGN: Population based birth cohort study. SETTING: The child health and education study (16,004 neonatal survivors born in one week in April 1970). SUBJECTS: Information available for 14,676 children. OUTCOME MEASURES: Clinical information and tests of intellectual performance at five and 10 years after birth. RESULTS: 19 children had lengthy febrile convulsions and 18 had status epilepticus. Two children with status epilepticus died (one at 5 years old); neither death was directly due to the status epilepticus. Four of the 19 (21%) developed afebrile seizures after lengthy febrile convulsions compared with 14 of the 17 (82%) survivors after status epilepticus. Measures of intellectual performance were available for 33 of the 35 survivors: 23 were normal and 10 were not normal but eight of them had preceding developmental delay or neurological abnormality. CONCLUSION: The outcome in children after lengthy febrile convulsions and status epilepticus is better than reported from studies of selected groups and seems determined more by the underlying cause than by the seizures themselves. PMID- 8369682 TI - Study of infection with HIV and related risk factors in young offenders' institution. AB - OBJECTIVES: To estimate the prevalence of infection with HIV in young offenders in Scotland and to obtain information about related risk factors and previous tests for HIV. DESIGN: Voluntary anonymous study with subjects giving saliva samples for testing for HIV and completing questionnaires about risk factors. SETTING: Polmont Young Offenders' Institution near Falkirk, Scotland. SUBJECTS: 421 of 424 available male prisoners in Polmont. The questionnaires of 17 of the prisoners were excluded because of inaccuracies. MAIN OUTCOME MEASURES: Prevalence of infection with HIV and related risk behaviour. RESULTS: 68 (17%) of prisoners admitted misuse of intravenous drugs, of whom 17 (25%) admitted having injected drugs while in prison. Three subjects admitted having anal intercourse while in prison. Prevalence of misuse of intravenous drugs varied geographically: 28% (33/120) of prisoners from Glasgow compared with 9% (7/81) of those from Edinburgh and Fife. A high level of heterosexual activity was reported, with 36% (142/397) of prisoners claiming to have had six or more female sexual partners in the year before they were imprisoned. Altogether 8% (32/389) of prisoners had previously taken a personal test for HIV: 50% (9/18) of those who had started misusing intravenous drugs before 1989, 18% (9/49) of those who started misuse later, and only 4% (14/322) of those who had not misused intravenous drugs. No saliva sample tested positive for antibodies to HIV, but 96 prisoners requested a confidential personal test for HIV as a result of heightened awareness generated by the study. CONCLUSIONS: Voluntary, anonymous HIV surveys can achieve excellent compliance in prisons, and the interest generated by the study suggests that prisons may be suitable sites for providing education and drug rehabilitation for a young male population at high risk of future infection with HIV. PMID- 8369683 TI - Lifelong exercise and stroke. AB - OBJECTIVES: To examine the potential of lifelong patterns of increased physical activity to prevent stroke. DESIGN: Case-control study. SETTING: 11 general practices in west Birmingham. SUBJECTS: 125 men and women who had just had their first stroke and were aged 35-74 and 198 controls frequency matched for age and sex recruited over 24 months during 1988-90. Exclusion criteria were a previous history of stroke, mitral valvular heart disease combined with atrial fibrillation, primary or metastatic cerebral neoplasm, or coagulation disorder or myeloproliferative disease. MAIN OUTCOME MEASURES: Odds ratios for stroke related to lifetime history of exercise after 15 years of age. RESULTS: A history of vigorous exercise during the ages 15-25 appeared to protect from stroke: odds ratio adjusted for age and sex 0.33 (95% confidence interval 0.2 to 0.6). This effect was independent of other potential risk factors. Increasing years of participation in vigorous exercise between the ages of 15 and 55 produced an increasing protection from stroke (p < 0.001). In the 65 cases and 169 controls who were free of cardiac ischaemia, peripheral vascular disease, and poor health recent vigorous exercise and walking were protective against stroke: odds ratios of 0.41 (0.2 to 1.0) for recent vigorous exercise and 0.30 (0.1 to 0.7) for recent walking. CONCLUSIONS: Appreciable protection from stroke in later life is conferred by vigorous exercise in early adulthood. This increased level of physical activity should, if possible, be continued lifelong. PMID- 8369685 TI - Microalbuminuria in chronic obstructive lung disease. PMID- 8369684 TI - Psychological distress in pregnancy and preterm delivery. AB - OBJECTIVE: To investigate if psychological distress during pregnancy is associated with increased risk of preterm delivery. DESIGN: Prospective, population based, follow up study with repeated measures of psychological distress (general health questionnaire), based on the use of questionnaires. SETTING: Antenatal care clinic and delivery ward, Aarhus University Hospital, Denmark. SUBJECTS: 8719 women with singleton pregnancies attending antenatal care for the initial visit between 1 August 1989 and 30 September 1991; 5872 women (67%) completed all questionnaires. MAIN OUTCOME MEASURE: Preterm delivery. Estimation of gestational age at delivery was mainly based on early ultrasound measurements. RESULTS: In 197 cases (3.6%) the woman delivered prematurely (less than 259 days). A dose-response relation between psychological distress in the 30th week of pregnancy and risk of preterm delivery was found, but distress measured in the 16th week was not related to preterm delivery. Control of confounding was secured by the use of multivariate logistic regression models. Relative risk for preterm delivery was 1.22 (95% confidence interval 0.84 to 1.79) for moderate distress and 1.75 (1.20 to 2.54) for high distress in comparison to low distress. CONCLUSIONS: Psychological distress later in pregnancy is associated with an increased risk of preterm delivery. Future interventional studies should focus on ways of lowering psychological distress in late pregnancy. PMID- 8369686 TI - Fine needle aspiration cytology in diffuse or multinodular goitre compared with solitary thyroid nodules. PMID- 8369687 TI - Erythema multiforme following substitution of amlopidine for nifedipine. PMID- 8369688 TI - Fluoxetine-warfarin interaction. PMID- 8369689 TI - Generalised seizure due to terfenadine. PMID- 8369690 TI - Opiate related collapse in an octogenarian. PMID- 8369691 TI - Is the cold chain for vaccines maintained in general practice? AB - OBJECTIVE: To investigate the cold chain for vaccines and compliance with the local code of practice for storage. DESIGN: In a random sample of general practices orders for live vaccines (oral polio and measles, mumps, and rubella) were accompanied by a cold chain monitor which was activated on leaving the supplying pharmacy. The monitors were read at specified intervals and when all vaccines in the order had been used. Structured interview was used to check compliance with the local code of practice on storage. SETTING: West Berkshire and Aylesbury Vale district health authorities. SUBJECTS: 16 (25%) general practices in West Berkshire, and 13 (50%) in Aylesbury Vale. MAIN OUTCOME MEASURES: Compliance with code of practice. Changes in the cold chain monitor. RESULTS: For six key requirements within the code of practice compliance varied from 70% to 0%. Only 16 of 29 practices had a named person responsible for vaccine storage and only four were aware of the local code of practice. Vaccine was stored for longer and more breaks in the cold chain occurred in West Berkshire than in Aylesbury Vale. The potency of some vaccines in 10 of 26 orders became suspect before use. CONCLUSIONS: Knowledge of appropriate management of the cold chain in two districts was poor. Breaks in the chain were more frequent and compromised potency more likely when vaccine had been stored for more than eight weeks. Problems in maintaining the cold chain indicate the need for continuing audit, which should become a prerequisite for payments to general practitioners for immunisation. PMID- 8369692 TI - Therapeutic aerosols in children. AB - The use and variety of drugs administered to children as inhaled aerosols is increasing, but little is known about how much drug reaches the lung and how it is distributed there in different age groups. In this article the reasons for measuring aerosol deposition in children are discussed and the potential methods for doing this described. Of the methods available, only the use of radiolabelled aerosols gives accurate information on total lung deposition and distribution. The potential risk of the radiation exposure required for these measurements varies with the age of the child but seems to be small. Properly designed studies are expected to clarify the factors affecting lung deposition in children and identify methods of inhalation associated with efficient and predictable delivery of the drug. Measurements of radioaerosol deposition may therefore be justified in children when this information is expected to lead to improvements in the effectiveness or safety of their treatment. PMID- 8369693 TI - Legal landmark for community care of former psychiatric patients. AB - A recent judgment of the Lands Tribunal has set an important precedent which should decrease the potential for restrictive covenants to thwart the development of the government's care in the community programme. In 1989 a Worthing couple were permitted to convert their own house into a residential care home for former psychiatric patients. Judge B Marder, QC, ruled on 12 January 1993 that the "public interest" outweighed a contractual stipulation that the property should be used only for residential, non-business purposes. This is a radical change in the Lands Tribunal's view of mental illness. PMID- 8369694 TI - Global regulations on diabetic treated with insulin and their operation of commercial motor vehicles. DiaMond Project Group on Social Issues. AB - Governments often regulate who may and may not drive vocationally for public safety purposes. Recent arguments, however, imply that employment opportunities may be limited unnecessarily for people with medical impairments. Drivers with diabetes treated with insulin are commonly perceived to pose an increased risk of accidents because of their susceptibility to hypoglycaemia. Much uncertainty, though, surrounds the data on the risks of these drivers. An international survey studied the licensing policies applied to professional lorry drivers with diabetes treated with insulin. Responses from 24 countries indicated that regulations differ considerably; ranging from a complete ban on professional driving to no restrictions at all. Many reasons may explain this difference, including the lack of data on the effects of hypoglycaemia on the incidence of traffic accidents. A proper account of the risks of diabetic drivers is necessary to balance fairly the rights of employment against the risks. PMID- 8369695 TI - Secondary adrenocortical insufficiency. PMID- 8369696 TI - NSAIDS in the postoperative period. Many factors threaten renal function. PMID- 8369697 TI - NSAIDS in the postoperative period...and after major surgery. PMID- 8369699 TI - The hazards of asbestos. Detailed occupational history is vital. PMID- 8369698 TI - NSAIDS in the postoperative period. Clinical experience confirms risk. PMID- 8369700 TI - The hazards of asbestos. Inaccurate diagnoses distort results. PMID- 8369701 TI - Management of uncomplicated miscarriage. Patients' safe with expectant management. PMID- 8369702 TI - Management of uncomplicated miscarriage. Randomized trials are possible. PMID- 8369703 TI - The hazards of asbestos. Access to vital data is denied. PMID- 8369704 TI - Delaying appendicectomy overnight. PMID- 8369705 TI - Bleeding complications after thrombolysis. PMID- 8369706 TI - Children's consent to treatment. Legal advice often unnecessary. PMID- 8369707 TI - Children's consent to treatment. Abstract debate is unhelpful. PMID- 8369708 TI - Analgesia for children in intensive care. PMID- 8369709 TI - Citizens' advice in general practice. Patients benefit from advice. PMID- 8369710 TI - Health care for prisoners ... by sympathetic medical staff. PMID- 8369711 TI - Health care for prisoners. Prison environment encourages conflict. PMID- 8369712 TI - Health care for prisoners. Whitemoor's inmates well cared for. PMID- 8369713 TI - Children are being denied intensive care. PMID- 8369714 TI - Diabetic services must match the patients. PMID- 8369715 TI - Screening for cystic fibrosis. Specialists get on with it. PMID- 8369716 TI - Insomnia in the chronic fatigue syndrome. PMID- 8369717 TI - Management of medical research. Room for improvement. PMID- 8369718 TI - Misrepresentation of epidural analgesia in labor. PMID- 8369720 TI - Management of medical research. Experience confirms directors' dissatisfaction. PMID- 8369719 TI - Management of medical research. Don't confuse management with administration. PMID- 8369721 TI - Management of medical research. Who exactly is in charge? PMID- 8369722 TI - Management of medical research. Management at MRC is modern and flexible. PMID- 8369723 TI - Management of medical research. Change requires a rational approach. PMID- 8369724 TI - Management of medical research. Judgement of science needs constant review. PMID- 8369725 TI - Management of medical research. Open up the evaluation process. PMID- 8369726 TI - Prevention of mural thrombus in porous inner tube of double-layered tube by saline perfusion. AB - An in vitro experiment under laminar nonpulsatile blood flow and an acute canine ex vivo femoral A-V series shunt experiment were undertaken to investigate the effectiveness of saline perfusion through pores of porous tubes to prevent formation of mural thrombus. PS/SBR porous tubes were used for the in vitro experiment. Commercially obtained ePTFE porous tubes were etched by sodium naphthalenide, and the etched tubes were used for the ex vivo experiment. According to the results of the in vitro experiment, mural thrombus on the surface of the porous tube could be prevented by the saline perfusion. Adhered blood cells decreased semi-logarithmically with increased perfusion rate (up to 0.022 ml/min-cm2) of isotonic saline solution. According to results of the ex vivo experiment, mural thrombus decreased with increased perfusion rate (up to 0.060 ml/min-cm2). PMID- 8369727 TI - Comparative study of the mechanical behaviour of Castaman external fixator in different mounting configurations. AB - The mechanical behaviour of the Castaman external fixator was determined using different mounting configurations in a system that simulated a long bone fracture during the formation of the bone callus. The first stage of the study was the determination of the stress-strain characteristics of the system with monolateral mounting. The second stage, the object of this study, is the analysis of the system with bilateral mounting and a comparison between the two configurations of the external fixator examined. Strain gauge analysis was used to determine the strains and stresses in the various elements of the system (fiches and external unit). Numerical techniques (FEM) were also used in order to confirm the results obtained using the simulation system. The results obtained show clearly the greater stiffness of the bilateral system. Combined bending and compressive stresses are present on both the screws and the external units, and reveal a little asymmetrical behaviour due to the conicity of the screws. PMID- 8369728 TI - Viscoelastic properties of stiff joints: a new approach in analyzing joint contracture. AB - The purpose of this study was to analyze the joint stiffness after immobilization in a rat's lower extremity model. Rat knee joints were surgically immobilized in a full flexed position for periods of up to 7 weeks with or without intra articular intervention. The biomechanical analysis was assessed by measuring the bone-joint-bone sample as a cantilever. Measurement was performed with (a) knee flexion angle with gravity, (b) fast Fourier transform analysis of time-dependent mechanical noise with random frequencies, and (c) dynamic stiffness and loss tangent with sinusoidal vibration at a certain frequency. The results showed that the conventional static mechanical test could not detect the intraarticular changes of the whole knee joint. The measurement of the viscoelastic properties covering wide frequencies revealed that an accurate change occurred. PMID- 8369729 TI - The role of ions and mineral-organic interfacial bonding on the compressive properties of cortical bone. AB - Bone tissue is a composite material composed of an inorganic stiff mineral phase embedded in a compliant organic matrix. Similar to other composites, the mechanical properties of bone depend upon the properties, volume fraction, and orientation of its constituents as well as the bonding interactions. Interfacial bonding between the mineral and organic constituents are based, in part, on electrostatic interactions between negatively charged organic domains and positively charged mineral surface. Phosphate and fluoride ions can alter mineral organic interfacial causing a permutation in the mechanical properties. Partial debonding between the mineral and organic constituents of bone may play an important role in the mechanical properties of aged and diseased bone. The present study examines the effects of phosphate and fluoride ion treatment on the compression properties of cortical bone and the reversibility of the effect. PMID- 8369730 TI - Prevention of blood cell adhesion in porous inner wall of double-layered tube by saline perfusion. AB - A double-layered tube consisting of a porous inner tube and a solid outer tube was used to perfuse isotonic saline solution into blood to prevent blood cell adhesion. Polystyrene/poly(styrene-co-butadiene) (PS-SBR) porous tubes were made using a dipping method. Citrated canine blood was circulated for 30 min with the flow rate of 100 ml/min using an in vitro blood circulation setup which makes nonpulsatile blood flow. Blood cell adhesion in the PS/SBR porous tubes decreased with increased saline perfusion rate regardless of changes in variables such as tube porosities, tube materials, and perfusion materials. The relationship between blood cell adhesion and perfusion rate was semi-logarithmic. Blood cell adhesion was relatively high in the more porous tube (65% sugar tube), compared to the less porous tube (55% sugar tube) for an identical saline perfusion rate. The blood cell adhesion in the sulfonated PS/SBR porous tube was less than that in the nonsulfonated (control) PS/SBR porous tube. The blood cell adhesion was also decreased by citrate perfusion. The results of this study indicates that the saline perfusion method can be used to prevent blood cell adhesion in the blood lines of extracorporeal circulation systems (such as hemodialysis and heart-lung machines) if certain technical problems involving the surface roughness can be resolved. PMID- 8369731 TI - Protein phosphorylation in the nerve terminal. PMID- 8369732 TI - Evidence of free radical damage in the central nervous system of guinea-pigs at the prolonged acute and early relapse stages of chronic relapsing experimental allergic encephalomyelitis. AB - Central nervous system tissue from guinea-pigs in various stages of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) has been analysed for evidence of free radical damage using the thiobarbituric acid test as an indicator of oxidative changes. Levels of thiobarbituric acid-reactive materials in brain and spinal cord regions from prolonged acute and early relapse phases of CR-EAE were significantly higher than in central nervous system tissue from Freund's adjuvant control and normal uninoculated animals. In the late relapse phase of CR-EAE, levels of thiobarbituric acid-reactive materials in CNS samples were at control values. Fluorescence analysis of central nervous system tissue confirmed evidence of increased free radical damage in prolonged acute and early relapse stages of CR-EAE. The increased oxidative damage observed in the central nervous system in CR-EAE is discussed in relation to the role of macrophages and their oxidative burst. PMID- 8369733 TI - Cocaine-sensitive and -insensitive dopamine uptake in prefrontal cortex, nucleus accumbens and striatum. AB - Behavioral studies have indicated that the reinforcing effects of cocaine are dependent on inhibition of dopamine uptake in nucleus accumbens and prefrontal cortex. As it has been suggested that dopamine uptake and cocaine-inhibition of dopamine uptake may differ in nucleus accumbens, prefrontal cortex and striatum, we have further characterized dopamine uptake and its susceptibility to inhibition in these three regions. Dopamine uptake was resolved into two processes, which accounts for some of the apparent reported regional differences in sensitivity of dopamine to inhibition by cocaine. One, which is probably associated with uptake into dopaminergic terminals, was sensitive to 6 hydroxydopamine lesions, cocaine, GBR 12909 or ouabain and was dependent on temperature and sodium ion concentration; this was responsible for most of the observed uptake in tissue from striatum and nucleus accumbens, but not from prefrontal cortex. There appeared to be no regional difference in susceptibility of this mode of dopamine uptake to either cocaine or GBR 12909. The other type of dopamine uptake, which represented a significant proportion of the total in prefrontal cortex, but not in striatum or nucleus accumbens, was relatively insensitive to cocaine, GBR 12909 and ouabain and was dependent on temperature, but not sodium ion concentration. In addition, the cocaine-insensitive dopamine uptake was more sensitive to inhibition by dopamine than serotonin, but did not distinguish between dopamine and norepinephrine. The occurrence of cocaine sensitive dopamine uptake in all examined regions and its equal sensitivity to cocaine and GBR 12909 is consistent with the involvement of nucleus accumbens and/or prefrontal cortex in the reinforcing effects of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369734 TI - Antiserum against neuropeptide Y enhances the nicotine-mediated release of catecholamines from cultured rat adrenal chromaffin cells. AB - A primary culture of chromaffin cells was prepared from adult rats and the stability of cell contents, NPY and catecholamines (CAs), during the culture was studied. The responsiveness of cultured chromaffin cells to NGF or secretagogues and the possible role of NPY on the CA secretion from cultured chromaffin cells were investigated. After plating of isolated cells, there was marked decrease in the cell content of CAs but a significant increase in the cell content of NPY. Though both NPY and CAs in the cultured cells were positively regulated by NGF, the results of this study seemed to suggest a differential regulation for NPY and CAs in the chromaffin cell. The cultured chromaffin cells secreted NPY and CAs in response to stimulation by nicotine. The nicotine stimulated secretion of CA was enhanced by the presence of IgG fraction, prepared from NPY antiserum, in the secretion medium. The results suggested that NPY was co-released with CAs from chromaffin cells and then acted as a modulator on CA secretion. PMID- 8369736 TI - The superoxide dismutase activities of cerebral tissues, assayed by the chemiluminescence method, in the gerbil focal ischemia/reperfusion and global ischemia models. AB - Superoxide dismutase is well known to act as an effective antioxidant enzyme against cellular damage caused by oxidative stresses including ischemia/reperfusion-induced cerebral injury. However, it is still controversial whether or not the activity of endogenous superoxide dismutase changes during cerebral ischemia and reperfusion. In order to elucidate this phenomenon, we assayed the superoxide dismutase activity in the cerebral tissues of gerbils using the chemiluminescence method with a Cypridina luciferin analog. This method was demonstrated to be a sensitive and specific assay for the enzymatic activity of superoxide dismutase in cerebral tissues, which was not subject to interference from proteins or ascorbate. After 3 h of focal and global ischemia, there were no changes in the cerebral tissue superoxide dismutase activities. After 24 h of reperfusion following 1 h of ischemia, the superoxide dismutase activity decreased only approx 20%, whereas the adenylate kinase activities, measured in the same cerebral tissues as those used for superoxide dismutase assay, started to decline 1 h after reperfusion commenced and were approx 50% of the control levels after 24 h. These results show that almost all the activity of endogenous superoxide dismutase is maintained and does not decrease significantly as a result of ischemia/reperfusion-induced cerebral injury. PMID- 8369735 TI - Selective masking of M1-receptors in calf retina membranes by the venom of the marine snail Conus tessulatus. AB - The non discriminatory antagonist [3H]QNB labels M1- and M2-muscarinic receptors in calf retina membranes. Crude venom from the marine gastropod Conus tessulatus produces a partial decrease in [3H]QNB binding. The total number of sites (560 +/ 13 fmol/mg protein in control experiments) decreases to 370 +/- 10 fmol/mg protein whereas the affinity of the radioligand is unaffected (KD = 0.42 +/- 0.01 nM and 0.46 +/- 0.02 nM, respectively). This process is venom concentration dependent, quasi-irreversible, and calcium-dependent. Proteolytic activity can not be detected. The partial effect of the venom is related to preferential masking of the M1-receptors. Competition curves of the M1-selective antagonist pirenzepine are shallow in control experiments: 45% of the receptors are of the M1-type (Ki = 45 +/- 6 nM) while the remaining are of the M2-type (Ki = 1.0 +/- 0.2 microM). In venom-treated membranes, only a low affinity site (M2-receptors, Ki = 1.5 +/- 0.4 microM) is detected by pirenzepine competition binding. Saturation binding experiments reveal that the venom causes a substantial decrease in the number of high affinity sites for [3H]pirenzepine without affecting its KD (23 +/- 4 nM and 20 +/- 6 nM in control- and venom-treated membranes respectively). The venom produces a leftward shift of the carbachol/[3H]QNB competition binding curve, but the ability of 0.1 mM GTP to confer a rightward shift of the competition curve is not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369737 TI - The subcellular distribution of [3H]-CGS 21680 binding sites in the rat striatum: copurification with cholinergic nerve terminals. AB - The subcellular distribution of the adenosine A2a receptor in rat striatum has been investigated using specific binding of the A2a-selective ligand [3H]-CGS 21680. After subcellular fractionation, the distribution of [3H]-CGS 21680 binding was similar to that of the cholinergic nerve terminal marker acetylcholinesterase rather than the more general membrane marker 5' nucleotidase, with 42% of binding associated with the synaptosomal sub-fraction and 19% with a light membrane fraction. Binding of [3H]-CGS 21680 was also found to co-purify with the cholinergic nerve terminal marker choline acetyltransferase during immunoaffinity purification of striatal cholinergic nerve terminals. These results demonstrate that some adenosine A2a receptors are present on cholinergic nerve terminals in rat striatum. PMID- 8369738 TI - Indole-pyruvic acid treatment reduces damage in striatum but not in hippocampus after transient forebrain ischemia in the rat. AB - The effects of treatment with indole-pyruvic acid, an endogenous metabolite of tryptophan converted into kynurenic acid in the brain, were studied in rats after transient forebrain ischemia induced by the 4-vessel occlusion procedure. The histological analysis showed a significant protective effect of indole-pyruvic acid treatment on striatal ischemic lesions assessed by the extent of regional atrophy and the area of neuronal disappearance 14 days after ischemia. Striatal neurons were labelled by dopamine and adenosine 3':5' monophosphate regulated phosphoprotein-32 immunoreactivity. Conversely, increased neuronal loss, regional atrophy and glial fibrillary acidic protein immunoreactivity, an index of post injury astroglial activation, were observed in the hippocampal formation, especially the CA3 field, of indole-pyruvic acid-treated rats when compared with vehicle-treated ischemic rats. The treatment with indole-pyruvic acid did not produce any improving effects in a test assessing short-term impairments after transient ischemia (motor test score at 24 h and 48 h post-ischemia). Furthermore, no significant effects of indole-pyruvic acid treatment were found on performance in water T-maze studied at 7 and 14 days post-ischemia. The opposite effects of indole-pyruvic acid on ischemic lesion in different brain regions may be related to its multiple neurochemical actions in the brain. The protective effect of indole-pyruvic acid on ischemic damage in striatum may be due to its conversion into kynurenic acid, a broad spectrum glutamate receptor antagonist. At hippocampal level, where glutamate receptor antagonists have been proved ineffective in the present lesion model, indole-pyruvic acid-induced changes in monamine availability may lead to a worsening of neuronal damage. PMID- 8369740 TI - Monosialoganglioside (GM1) restores membrane fatty acid levels in ischemic tissue after cortical focal ischemia in rat. AB - Using a consistent, reproducible and reliable cortical focal ischemia in rat (permanent unilateral occlusion of the left middle cerebral artery & the ipsilateral common carotid artery [MCAo + CCAo] with a 1 h temporary occlusion of the contralateral CCA), the levels of four major membrane fatty acids (palmitic, C16:0; stearic, C18:0; Oleic, C18:1 and arachidonic, C20:4) were analyzed at 3, 36 and 72 h, and 2 and 4 wk following ischemia to determine the critical point of irreversibility of the cellular plasma membrane disorganization in primary ischemic (Area 1, parietal cortex) and peri-ischemic (Area 2, tempero-occipital cortex) areas. The cortical focal ischemia resulted in time dependent differential loss in four of these major membrane fatty acids. The quantitative differences among primary and peri-ischemic areas reflected the different degree of ischemic injury inflicted to these regions. Acute treatment with ganglioside GM1 protected the further losses of all of these fatty acids and differentially restored their levels in these various injury sites over periods of time. The changes in levels of these membrane fatty acids indicate that the primary ischemic area suffers an irreversible injury and peri-ischemic area suffers reversible injury. After acute treatment (< 2 h) with ganglioside GM1, a partial recovery was observed in primary ischemic area and complete recovery was observed in peri-ischemic areas. These studies support the hypothesis that, ischemia leads to a irreversible plasma membrane disorganization which underlies the eventual cell death, and protection and restoration of these membrane changes by drugs, such as ganglioside GM1 leads to neuroprotection against ischemic injury. PMID- 8369739 TI - Aging does not affect the susceptibility to lipid peroxidation and lysosomal enzyme release of rat visual system structures and sciatic nerve. AB - The aim of the present study was to clarify the issue of lipid peroxidation operating in visual system structures and sciatic nerve of the rat as a contributing factor to senescence. In 4-, 14- and 28-month-old male rats, the amount of endogenous malondialdehyde, conjugated dienes and extractable phospholipids were all taken as indices of lipid peroxidation. In addition, the total free and released enzyme activities of four lysosomal hydrolases were evaluated. The susceptibility of all these parameters to in vitro iron-induced peroxidation was also taken as an age-related indicator of the endogenous peroxidative potential of the nervous tissues examined. Our data show that the content of malondialdehyde and phospholipids did not change in an age-related fashion. Furthermore, the susceptibility of rat visual system structures to lipid peroxidation, together with the release of lysosomal enzymes were unchanged as a function of aging. The results do not lend support to the hypothesis that an increase in overall lipid peroxidation is peculiar to the aging phenomenon of the central nervous system areas which delimit the rat visual pathway. PMID- 8369741 TI - Intracellular formation and release of adenosine from rat hippocampal slices evoked by electrical stimulation or energy depletion. AB - In this study, the basal and evoked release of [3H]- and endogenous adenosine, inosine and hypoxanthine from rat hippocampal slices, labelled with [3H]adenine, was investigated. Evoked release was brought about by either electrical stimulation or energy depletion. The aim was to determine whether adenosine is formed intracellularly, and released as adenosine or extracellularly, from sequential extracellular hydrolysis of released ATP. All measurements were made in the presence of 5 microM erythro-9-(2-hydroxy-3-nonyl) adenosine (EHNA) to inhibit the enzyme adenosine deaminase. It was found that electrical field stimulation (5 min) increased the release of endogenous adenosine from hippocampal slices 10-fold and increased the proportion of [3H]-label associated with adenosine from approx 7% of the total released to 13% after the first stimulation and 20% after the second stimulation. Removal of oxygen and glucose from the superfusion medium (energy depletion) increased the release rate of endogenous adenosine 16-fold and increased the proportion of [3H]-label associated with [3H]adenosine from approx 10% of the total released to 50%. In order to prevent extracellular formation of adenosine, experiments were carried out in the presence of 50 microM alpha, beta-methylene ADP (AOPCP), an inhibitor of ecto-5'-nucleotidase. AOPCP was found to be without effect on either the basal or evoked release of adenosine. In contrast, L-homocysteine thiolactone (0.1-1.0 mM) which was used to "trap" intracellular adenosine reduced both the basal and evoked release of adenosine by 70-85%. This effect of L-homocysteine thiolactone also occurred in the presence of adenosine uptake inhibitors. It is concluded from these results that adenosine is formed predominantly intracellularly in hippocampal slices and is released as adenosine as a result of either tissue depolarisation or energy depletion. Furthermore, the finding that during energy depletion there is a proportionally greater release of adenosine than other ATP breakdown products, such as inosine and hypoxanthine, indicates that energy depletion is both a potent and selective stimulus for adenosine formation and release. PMID- 8369742 TI - Action of myenteric GABAergic neurons in the guinea pig stomach. AB - GABAergic neurons in the guinea pig stomach were localized immunocytochemically using antibodies against its synthesizing enzyme, L-glutamate decarboxylase (GAD). Numerous ganglion cells and nerve bundles in the myenteric plexus were found to be GAD-positive, while the longitudinal muscle, submucosa and mucosa were largely devoid of GABAergic innervation. The distribution of GABAergic neurons and their processes in both myenteric ganglia and circular muscle is rather uneven throughout the stomach. GABA elicited contraction of the longitudinal fashion (LF) strips of the body and antrum of guinea pig stomach in a concentration-dependent fashion with a maximal response at 10(-7) M and 10(-5) M, respectively. GABA-induced contraction appears to be mediated by the GABAA receptor and not the GABAB receptor, since the action is blocked by bicuculline, a GABAA receptor antagonist. Furthermore, GABAA agonists e.g. muscimol produced even stronger responses than GABA itself while GABAB agonist, (-)baclofen had no effect in eliciting muscle contraction. The GABAA receptor is desensitized by prolonged exposure to its agonists such as GABA and muscimol. However, no such desensitization was observed for the muscarinic cholinergic receptor. The GABA action in eliciting smooth muscle contraction seems to involve two components, one is scopolamine and tetrodotoxin (TTX) sensitive, and the other one is insensitive to scopolamine and TTX. It is proposed that the scopolamine- and TTX sensitive component acts through a direct or indirect interaction between GABAergic and cholinergic neurons whereas the scopolamine- and TTX-insensitive component acts directly upon the smooth muscle. PMID- 8369743 TI - Purification and characterization of Silurus asotus (catfish) roe lectin. AB - A rhamnose-binding lectin isolated from Silurus asotus (catfish) roe by DEAE cellulose ion exchange and galactose-Sepharose affinity chromatographies predominantly agglutinated human type B and rabbit erythrocytes. S. asotus lectin (SAL) also agglutinated sarcoma 180 ascites carcinoma cells, but not AH109A cells. The most effective saccharide in hemagglutination inhibition assay was L rhamnose. The monosaccharides possessing steric similarity to the hydroxyl group orientation at C2 and C4 of the pyranose ring structure of L-rhamnose, such as L mannose and L-lyxose, were also effective. The molecular weight of SAL was determined to be 38000 by size exclusion chromatography on TSK gel G3000SW and 33000 by SDS-polyacrylamide gel electrophoresis under reducing conditions. SAL did not require a Ca2+ ion or free thiol group for its agglutination activity. The N-terminal 29 amino acid sequence was determined by a gas-phase sequencer as follows, ANMITCYGDVQKLHXETGLIIVKSXLYGR (X: not determined). It has no homology to the sequences of well known vertebrate lectins. PMID- 8369744 TI - Site-specific inactivation of papain by ascorbic acid in the presence of cupric ions. AB - The mechanism of inactivation of papain (EC 3.4.22.2) by ascorbic acid (AsA) in the presence of cupric ions (Cu2+) was investigated. The aerobic combination of Cu2+ and AsA resulted in an irreversible loss of enzyme activity. The inactivation was found to be an apparent first order reaction. The prior mixing of Cu2+ and AsA caused the complete disappearance of the inactivation. The addition of iron ions led to significant suppression against the inactivation. Cu2+ was bound to the enzyme in a molar ratio of 1:1. At lower concentrations of Cu2+ (molar ratio of enzyme to Cu2+ of 1: < 1), the extent of inactivation showed the same dependence against the extent of oxidation of AsA. The rate of inactivation increased as the concentration of AsA was increased. Saturation kinetics were observed with respect to the concentration of AsA. Changes in the concentration of Cu2+ had no effect on the dissociation constant of the enzyme AsA complex (KI), though the rate constant of inactivation (k2) showed a linear relationship with the concentration of Cu2+. At various pH values tested, no change of k2 was found, whereas the value of KI increased when the pH bacame lower. At higher concentrations of Cu2+, the rate of inactivation fell beyond a certain concentration of AsA. The present results suggest that both Cu2+ and AsA bind to the enzyme to form a ternary complex and that free radicals are site specifically formed and react preferentially with the enzyme, at the site of their formation, impairing its activity. PMID- 8369745 TI - Effects of lipid peroxidation on surface charge density of the porcine intestinal brush-border membranes. AB - The effects of lipid peroxidation on the surface charge density of the porcine intestinal brush-border membranes were studied using an oxygen-radical-generating system consisting of ascorbic acid, ferrous ion and tert-butyl hydroperoxide (tert-BuOOH). Changes in the membrane surface charge density were monitored using a fluorescent dye, 8-anilino-1-naphthalenesulfonate (ANS). The incubation of the membranes with ascorbic acid/Fe2+/tert-BuOOH resulted in a decrease of the fluorescence intensity of the ANS-membrane complex with a red-shift in the emission maximum, depending on the hydroperoxide concentration and the incubation time. The kinetic studies on ANS-binding showed that the apparent dissociation constant of ANS-membrane complex decreased by treatment with ascorbic acid/Fe2+/tert-BuOOH. Similar results were also obtained by treatment of the membranes with other oxidizing systems, hematin/tert-BuOOH and dipyridyl/Fe2+/tert-BuOOH. These results proposed the possibility that lipid peroxidation of the membranes causes an increase of the positive charge on the membrane surface. The results of the dependence of the ionic strength with increasing KCl concentrations in the medium upon the ANS-binding affinity for the membranes further supported this interpretation. PMID- 8369746 TI - Characterization of two acidic polysaccharides having immunological activities from the root of Panax ginseng. AB - Two acidic polysaccharides, named ginsenan PA and ginsenan PB, were isolated from the root of Panax ginseng C. A. Meyer. They were homogeneous on electrophoresis and gel chromatography, and their molecular masses were estimated to be 1.6 x 10(5) and 5.5 x 10(4), respectively. They are composed of L-arabinose: D galactose: L-rhamnose: D-galacturonic acid: D-glucuronic acid in the molar ratios of 11:22:1:6:1 (ginsenan PA) and 3:7:2:8:1 (ginsenan PB), in addition to small amounts of O-acetyl groups. Almost all (ginsenan PA) and part (ginsenan PB) of the hexuronic acid residues exist as methyl esters. Reduction of carboxyl groups, methylation analysis, nuclear magnetic resonance and periodate oxidation studies indicated that their structural features include mainly both alpha-arabino-beta 3,6-galactan type and rhamnogalacturonan type structural units. Both polysaccharides showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test, pronounced anti-complementary activity and alkaline phosphatase-inducing activity in a dose dependent manner. PMID- 8369747 TI - The amino acid sequence of neocarzinostatin apoprotein deduced from the base sequence of the gene. AB - A segment of the neocarzinostatin apoprotein gene corresponding to T30 to A91 of the protein was amplified using a polymerase chain reaction (PCR) with total DNA from Streptomyces carzinostaticus subsp. neocarzinostaticus E-793 (ATCC 15944) as the template and with 5'- and 3'-primers synthesized in consideration of the codon usage of streptomyces. The PCR product was cloned, sequenced and confirmed to direct an amino acid sequence reasonably well matching that reported. Using the PCR product as a probe, we cloned a DNA segment (2580 bp) spanning an open reading frame (ORF) for preapoprotein (leader peptide plus apoprotein) and its upstream and downstream flanking regions. The amino acid sequence deduced from the base sequence of the DNA clearly identified those amino acid residues which had remained inconsistent among different research groups. The base sequence homology with other apoprotein genes of related antibiotics was analyzed and was found to be limited within the structural gene. PMID- 8369748 TI - Local cerebral glucose utilization in rats with decerebrate rigidity and effects of centrally acting muscle relaxants, diazepam and tizanidine. AB - Local cerebral glucose utilization (LCGU) was investigated in rats with decerebrate rigidity using the [14C]2-deoxyglucose (2DG) method in order to identify the site responsible for the rigidity. LCGU was increased in the medial vestibular nucleus, the fastigial nucleus, the interpositus nucleus and the dentate nucleus during decerebrate rigidity. Diazepam and tizanidine, centrally acting muscle relaxants, reduced the increase of LCGU in the vestibular and cerebellar nuclei. These results suggest that the vestibular and cerebellar nuclei are the possible sites responsible for the development of decerebrate rigidity and the action of some centrally acting muscle relaxants. PMID- 8369749 TI - Possible antifertility agents belonging to substituted indoles. AB - Of the 21 compounds evaluated for antiimplantation and abortifacient activities, compounds (A1, A2, A4 and B1) and compounds (C1, C2, D1 and D3) were found to exhibit 40% and 30% antiimplantation activity, respectively, in female rats when given orally on days 1-5 postcoitum. The remaining 13 compounds were found to be inactive. All of the 21 compounds were also tested for the abortifacient activity, but all were found to be inactive. PMID- 8369750 TI - Lack of stereoselectivity in rat liver peroxisomal enzyme induction by optically active phenoxyacetic acids. AB - To ascertain if there is stereoselectivity in peroxisomal proliferation induced by chiral peroxisome proliferators, induction by stereoisomers of 2-methyl-4' chlorophenoxyacetic acid and 2-methyl-2-(2'-4'-dichlorophenoxy)acetic acid were studied in rat in vivo and in vitro with isolated rat hepatocytes. No significant differences in the inducing potencies of the stereoisomers of the above two phenoxyacetic acid derivatives were found for cyanide-insensitive fatty acyl-CoA oxidizing system, fatty acyl-CoA oxidase, carnitine acetyltransferase or carnitine palmitoyltransferase. There was also no significant difference in the degree of hepatomegaly or lipid-lowering effect between the isomers. The findings with cultured rat hepatocytes agreed with those of the studies in vivo. PMID- 8369751 TI - Pharmacokinetics of novel hexapeptides with neurotensin activity in rats. AB - A high-performance liquid chromatographic method to determine (Me)Arg-Lys-Pro-Trp tert-Leu-Leu (NT-2) with neurotensin (NT) activity in rat plasma was developed and a pharmacokinetic study was performed in rats. Quantitative analysis with high reproducibility was achieved for NT-2 over the concentration range of 1.14 500 ng/ml. (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt (NT-1) was rapidly hydrolyzed to NT-2 in rat plasma at 37 degrees C. This degradation of NT-1 was observed as a pseudo first-order reaction, and the pseudo first-order rate constant was calculated to be 7.26 min-1 (t1/2 = 0.095 min). The pharmacokinetic profiles of NT-2 after intravenous administration of NT-1 at doses of 0.1 and 0.3 mg/kg were compatible with that of NT-2 after intravenous administration of NT-2 at 0.5 mg/kg. Range of the half-life of the terminal phase (t1/2 beta) of NT-2 was 0.36 0.53 h. The absolute bioavailabilities after oral administrations of NT-1 and NT 2 at a dose of 20 mg/kg were 0.61 +/- 0.17 (mean +/- S.E.) and 0.19 +/- 0.08%, respectively. It was found that NT-1 was more suitable for oral administration than NT-2. PMID- 8369752 TI - Pharmacokinetic characteristics and antitumor activity of the N-succinyl-chitosan mitomycin C conjugate and the carboxymethyl-chitin-mitomycin C conjugate. AB - The conjugate between N-succinyl-chitosan (Suc-chitosan) and mitomycin C (MMC), named Suc-chitosan-MMC, and that between carboxymethyl-chitin (CM-chitin) and MMC, named CM-chitin-MMC, were investigated in vivo. As for the intraperitoneal drug administration using rats, the order of the maximum blood concentration of MMC was unconjugated MMC > CM-chitin-MMC > Suc-chitosan-MMC. The plasma concentration of MMC for Suc-chitosan-MMC was maintained at an almost constant level over 24 h. Pharmacokinetic analysis of each plasma concentration indicated that for each conjugate, the in vitro drug release reported previously was useful for the approximate estimation of the in vivo regeneration of MMC. The chemotherapeutic effect of MMC and the conjugates was investigated using mice bearing L1210 leukemia or B16 melanoma. Concerning antitumor activity against L1210 leukemia, the conjugates exhibited a marked effect at higher doses, and their effect increased even in the dose range where the effect of MMC decreased. MMC and the conjugates exhibited a good growth-inhibitory effect against B16 melanoma. Complete inhibition of growth of B16 melanoma was observed at the dose of 10 mg eq MMC/kg for CM-chitin-MMC. PMID- 8369753 TI - A study of cis-diamminedichloroplatinum(II) suppositories for the treatment of rabbit uterine endometrial carcinoma. AB - cis-Diamminedichloroplatinum (II) (cisplatin: CDDP) suppositories containing NaCl at different concentrations were prepared as a local chemotherapeutic agent for the treatment of uterine endometrial carcinoma and were administered to rabbits implanted with uterine VX2 tumor. The intrauterine CDDP histological level, as well as the antitumor effects and side effects of the suppositories to the liver and kidney were studied. The results showed high intrauterine tissue CDDP level in all suppository administrations. In particular, the NaCl-added suppositories enhanced the intrauterine CDDP level. As for antitumor effects, while the tumor growth rate of the NaCl-added suppository group was likely to be suppressed, the suppositories could not suppress tumor growth completely. The plasma platinum (Pt) level was 1.5 micrograms/ml or less and that of the liver and kidney was as low as 0.31 to 0.48 micrograms/g. No difference in levels depending on NaCl concentration was observed, nor was any abnormality found in the biochemical analysis including glutamate oxaloacetate transaminase (GOT) and blood urea nitrogen (BUN). Histopathological study revealed the degeneration of tumor cells in the NaCl-added suppository group. Minimal congestion and hemorrhage were observed in the endometria, possibly resulting from CDDP. By adding NaCl to CDDP suppositories, the uterine CDDP level and antitumor effects increased while no serious renal dysfunction was noted. Therefore, we conclude that NaCl-added CDDP suppositories are a useful local chemotherapy for endometrial carcinoma. PMID- 8369754 TI - Population pharmacokinetics of theophylline. I: Intravenous infusion to children in the acute episode of asthma. AB - The population pharmacokinetics of theophylline during constant-rate intravenous infusion has been studied in 66 children (8.7 +/- 4.7 year of age; 26.0 +/- 12.8 kg, mean +/- S.D.) with an episode of acute asthma. One hundred and twelve theophylline serum concentrations (13.9 +/- 4.8 micrograms/ml) collected retrospectively were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, age, gender, days after admission, blood gas measurements (PaO2, PaCO2, blood pH) and clinical analyses data (total serum protein, albumin concentration, haemoglobin concentration, haematocrit) on theophylline clearance was examined by the likelihood ratio test. A final estimate of population mean clearance was 58.6 ml/kg/h, which was decreased by 36% in patients with hepatic dysfunction. Other factors tested displayed no statistically significant effect on theophylline clearance. The inter-individual variability in clearance was 26% while the intra-individual variability in theophylline concentrations was 2.6 micrograms/ml as a standard deviation, which was almost double that observed for stable patients. Taking into account that the therapeutic window of this drug is 10-20 micrograms/ml, this value indicates a relatively large intra-individual variability and suggests that frequent (daily) monitoring of serum concentrations is necessary for patients with an episode of acute asthma. PMID- 8369755 TI - The influence of increased plasma protein binding on the disposition of quinidine in turpentine-treated rats. AB - The effect of the increased plasma protein binding of quinidine on its disposition was investigated in turpentine-treated rats, since turpentine treatment is known to increase the plasma concentration of alpha 1-acid glycoprotein which preferentially binds basic drugs. The plasma free fraction of quinidine 16 and 48 h after turpentine treatment was decreased by 30 and 76%, respectively, compared to the control value. The treatment did not cause liver injury nor alter the hepatic blood flow. The disappearance of quinidine in plasma after an intravenous injection (3.0, 7.0, 12.5 mg/kg) was analyzed by a two compartment open model in both control and turpentine-treated rats. The blood total body clearance (CLb) of quinidine at 48 h after the treatment was decreased by 30 to 65% in a dose-dependent manner, compared to that in control rats. The distribution volume (Vdss) of quinidine (12.5 mg/kg) at 16 and 48 h after turpentine treatment was decreased by 30 and 79%, respectively. Hepatic extraction ratio (HER) of quinidine, which was determined at steady state blood concentrations from 0.5 to 2.3 micrograms/ml, was decreased from 0.8 to 0.35 with an increase in the quinidine concentration in control rats. The HER value 48 h after turpentine treatment was consistently reduced by 15 to 40% in a concentration-dependent manner compared to the corresponding control value. These findings indicate that the increased plasma binding of quinidine caused a reduction of HER of the drug, and the reduced HER resulted in the decrease in CLb in turpentine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369756 TI - Systemic effects of epidermal growth factor (EGF) ointment containing protease inhibitor or gelatin in rats with burns or open wounds. AB - The systemic effects of epidermal growth factor (EGF) ointment containing nafamostat (NM), gabexate, or gelatin was studied in rats with burns or open wounds. At 1 d after burn, plasma epinephrine, cortisol, and glutamic-oxalacetic transaminase (GOT) levels were elevated, but treatment with EGF plus NM (EGF+NM) ointment significantly suppressed the increase in these levels. Further, there was no loss of body weight in the open wound model following treatment with EGF+NM ointment, while loss of body weight occurred in animals in which EGF ointments without NM were applied. Increases in plasma epinephrine 1 d after open wound formation were also suppressed by the application of EGF+NM ointment. Treatment with EGF ointment containing gabexate (GX) or gelatin (GL) ameliorated changes in body weight that occurred after open wound formation, while loss of body weight in animals with open wounds occurred following the application of ointment base, EGF ointment, GX ointment, or GL ointment. The present study thus indicates that the topical application of EGF ointment containing a protease inhibitor has ameliorative systemic effects. PMID- 8369757 TI - Detection of tetracycline resistance protein encoded by Bacillus subtilis plasmid pNS1. AB - Tetracycline resistance protein (TET) of Bacillus subtilis plasmid pNS1 was detected by immunoblot analysis using a specific antibody to TET-chloramphenicol acetyltransferase (CAT) fusion protein. In two-dimensional electrophoresis, one major spot which seemed to be the pNS1-encoded TET (pNS1-TET), was detected by immunostaining. Its molecular weight and isoelectric point were approximately 52 kDa and 6.2, respectively. Judging from the nucleotide sequence, the pNS1-TET is a very hydrophobic, 50 kDa protein. Therefore, the 52 kDa protein is thought to be an intact form of the pNS1-TET produced by B. subtilis cells. PMID- 8369758 TI - Accumulation of (E)-4-hydroxy-2-nonenal and n-hexanal, degradation products of lipid peroxides, in mouse lung and liver. AB - Effects of lipid peroxide breakdown products, (E)-4-hydroxy-2-nonenal (4-HN) and n-hexanal, on mouse lung lesion were examined. When 4-HN was injected i.v., the plasma level of 4-HN increased just after the injection and then decreased immediately. The amounts of 4-HN increased in the liver and lung were ca. 0.085 and 0.43% to the dose administered, respectively, 5 min after the injection. Reduced glutathione (GSH) content and both GSH peroxidase (GSH-Px) and GSH reductase (GSSGR) activities in the lung were decreased significantly by 4-HN treatment. On the other hand, in the case of i.v. injection of n-hexanal into mice, the amount of n-hexanal detected in the lung was 5.0% to that of 4-HN, and no effect on the activities of GSH-Px and GSSGR and the content of GSH was observed. These results suggest that 4-HN generated from lipid peroxides would be transferred into the lung and cause the lung lesion through the inhibition of GSH dependent antioxidative defense systems. PMID- 8369759 TI - Recognition of a palindromic DNA sequence by ESF-1, a factor stimulating transcription of the adenovirus type 12 E1A gene. AB - We previously identified a factor, designated E1A-stimulating factor 1 (ESF-1), that stimulates transcription of the adenovirus type 12 E1A gene in vitro by binding to a region next to a TATA box. We report here on the partial characterization of the mode of ESF-1 action. Point mutations within the nucleotide sequence 5'-TCAGCTGA-3' abolished the binding of ESF-1. Stimulation of transcription of the adenovirus type 12 E1A gene in vitro was lost when a 7 base pair insertion was introduced between the ESF-1-binding site and a TATA box. These results suggest that ESF-1 stimulates adenovirus type 12 E1A gene transcription by interacting with a palindromic DNA sequence present in a region immediately upstream from a TATA box. PMID- 8369760 TI - Further differentiation of 2'- and 4'-chloroflavones as inducers of hepatic microsomal monooxygenases in rats. AB - 2'-Chloroflavone (CF) and 4'-CF were studied as inducers of cytochrome P-450 mediated monooxygenases in rat hepatic microsomes by comparison with phenobarbital (PB) and 3-methylcholanthrene (MC). As a result of interaction with the substrate 7-ethoxycoumarin (7-EC), 2'-CF-induced microsomes showed a difference spectrum different from usual type I, whereas 4'-CF-induced microsomes showed a typical type I spectrum. 2'-CF-induced microsomes increased the Vmax of aminopyrine (AM) N-demethylase activity about 1.6-fold while not affecting the apparent Km value. In contrast, 4'-CF-induced microsomes decreased the Km of 7-EC O-deethylase activity to about one fourth while significantly increasing the Vmax value. All the activities of AM N-demethylase, 7-EC O-deethylase and 6,7 dimethoxycoumarin O-demethylase in 2'-CF-induced microsomes were inhibited strongly by metyrapone and SKF 525-A, and significantly by diphenhydramine. The three enzyme activities in 4'-CF-induced microsomes were inhibited markedly by alpha-naphthoflavone and significantly by 2-bromo-4'-nitroacetophenone. These results further support the previous proposal that 2'-CF is a PB-type inducer of cytochrome P-450 while 4'-CF is a MC-type inducer. PMID- 8369761 TI - Autooxidation of alkylhydrazones and mutagenicity of the resulting hydroperoxides. AB - Acetone alkylhydrazones were readily autooxidized to 2-alkylazo-2-propyl hydroperoxides, which were directly mutagenic in Salmonella typhimurium TA1535, TA100, TA102 and Escherichia coli WP2hcr. The mechanism of this mutagenicity presumes that the hydroperoxides in aqueous solution decompose to alkyl diazonium ions which were observed in the alkylation of 4-(p-nitrobenzyl)pyridine, and also to hydroxyl radical which was detected by ESR. PMID- 8369762 TI - Why battering during pregnancy? AB - This exploratory study was designed to determine the reasons men might beat their female partners during pregnancy from the perspectives of women who had experienced this form of violence. Seventy-nine battered women were recruited by newspaper advertisement and bulletin board postings to take part in a larger study of women's responses to relationship problems. Women battered in their relationships were asked if they had ever been beaten during pregnancy. The 27 (34%) women who had a pregnancy with the abusive partner as the father and had experienced physical abuse during the pregnancy were compared with 24 (30%) women who also had been pregnant by the abuser but had not been abused during pregnancy. The only significant difference between the two groups was that the women battered during pregnancy were more frequently and severely beaten throughout the course of the relationship. Those abused during pregnancy were asked why they thought that had happened. Their answers were thematically analyzed into the categories: (1) jealousy of the unborn child; (2) anger toward the unborn child; (3) pregnancy-specific violence not directed toward the unborn child; and (d) "business as usual." Implications for nursing assessment and interventions for abuse during pregnancy are derived from this analysis. PMID- 8369763 TI - Abuse during pregnancy: the horror and the hope. AB - Physical violence against women is pervasive; and such abuse may begin during pregnancy. This article chronicles the clinical research on battering during pregnancy and focuses on a prospective study of 691 pregnant women; the study documented that one in six women are abused during pregnancy. Ethnic differences in the patterns of abuse are discussed, as are related findings of entry into prenatal care and characteristics of the abuser. Clinical implications are presented, with an emphasis on the usefulness of straightforward assessment with a three-question abuse assessment screen to identify abused women and intervene to prevent abuse during pregnancy. PMID- 8369764 TI - Abuse of adolescents: what can we learn from pregnant teen-agers? AB - One of the most perplexing issues for nurses working with abused women is the extent of violence experienced by teen-agers. This article presents research findings from a study of pregnant women and teen-agers in Baltimore and Houston that found 32% of pregnant teen-agers reported having been physically or sexually abused in the prior year. The rate of abuse during pregnancy was 22% for teen agers. Teen-age violence is discussed in terms of possible reasons for teen-agers to be reluctant to report abuse and nursing considerations in the assessment and intervention of adolescents experiencing abuse. PMID- 8369765 TI - Nursing interventions for abused women on obstetrical units. AB - Battering is a public health problem that traditionally has been ignored by nurses, which has conveyed acceptance and approval of violence. Using the Betty Neuman Health Care System Model, nurses on obstetrical units can understand the health effects battering has on the mother and infant. Battering puts the woman at serious risk. By systematically addressing this stressor, nurses can improve the health and quality of life of the mother and newborn. PMID- 8369766 TI - Exploration of women's identity: clinical approaches with abused women. AB - This article outlines clinical approaches with women in abusive relationships or those who recently have left such situations. A model, the process of entrapment in and recovering from an abusive relationship, describes the experience of women in abusive relationships with a male partner and the cumulative influence of these experiences on women's views of self. This model has served as the basis for the development of specific interventions designed to assist women at different points in time while they experience abuse in a relationship or are recovering from the experience of being abused. PMID- 8369767 TI - What helped most in leaving spouse abuse: implications for interventions. AB - Women who are leaving abusive relationships rely on social support. However, their descriptions of the process of leaving, their reasons for leaving, and what helped them most in leaving relate to issues about the self as much as the availability of support. Clinicians who consider both of these resources can better support the decision making of women who are living in and leaving abusive male partners. PMID- 8369769 TI - Screening for abuse in the clinical setting. AB - Physical examinations can be positive patient experiences, providing reassurance, education, and case finding. However, examinations also can be extremely anxiety provoking because of feelings of shame and embarrassment about visible injuries from an abuser. They also may provoke flashbacks related to incest, child sexual abuse, and rape. Nurses involved in clinical assessment of any kind need to be aware that a patient's history often affects her response to clinical evaluation. Asking a patient about abuse before evaluation is respectful and empowering and often establishes a valuable opportunity for intervention. PMID- 8369768 TI - Sexual abuse within adult intimate relationships. AB - An intimate partner's initiation of forced sex may signal the escalation of tyranny in physically abusive relationships and failed plans to obtain mutual consent for sexual intercourse in dating relationships. Providers of obstetric and gynecologic care are in strategic positions for primary detection of and intervention in physical and sexual abuse. To assist nurses with the understanding of women's responses to abuse and to enhance implementation of interventions, this article describes the dynamics of and a process for intervening in such abuses. The dynamics include brief explanations of its insidious development, why women stay, and women's empowerment for coping with physical, emotional, and sexual abuse. Beginning with asking about the abuse, the process progresses through short-term goals, safety issues, and intervention techniques. PMID- 8369770 TI - Nursing care of African-American battered women: Afrocentric perspectives. AB - The focus of this article is on prominent Eurocentric beliefs, attitudes, and behaviors that may prevent African-American battered women from receiving effective intervention by health care professionals and other providers. Afrocentric perspectives are presented to provide an alternative context for understanding the traditions, beliefs, and behaviors that should be considered when providing care for African-American battered women. These perspectives are integrated into discussions of suspected contributions to the incidence of violence in the lives of African-American women. They also are incorporated into suggested interventions and a case study exploring nursing considerations that may be unique to providing effective care for African-American battered women. PMID- 8369771 TI - Nursing care of low-income battered Hispanic pregnant women. AB - Nurses working with pregnant Hispanic women can create barriers in the health care system by not understanding or accepting the variety of ways in which the Hispanic culture perceives and treats pregnancy. This article describes nursing care of low-income, battered Hispanic pregnant women within the context of the Hispanic culture and discusses clinical and nursing implications for interventions. To deliver effective culturally competent care to battered Hispanic pregnant women, nurses need to have a thorough understanding of the variables that influence the health care of Hispanics in the United States, such as the scope of wife abuse in the Hispanic population, sociodemographic characteristics of the Hispanic population in the United States, Hispanic women's access to health care, pregnancy in the Hispanic population, and health care practices of Hispanics in the United States. This will facilitate screening, education, and guidance without upsetting the often precarious security of this period. PMID- 8369772 TI - Nursing care of Native American battered women. AB - Native American nations and peoples have experienced hundreds of years of oppression, prejudice, poverty, and the lack of self-determination. This has resulted in a disintegration of self-esteem and traditional values that are manifested in high rates of self-inflicted injury and other violence, including suicide, homicide, alcoholism, and domestic violence. Nurses have a key role to play in addressing violence in Native American communities. Cultural sensitivity is central to effective intervention. PMID- 8369773 TI - Violence in transience: nursing care of battered migrant women. AB - Nurses working with migrant farm worker women face serious challenges. Poverty, language, and cultural differences between farm worker women and health care providers present substantial barriers to women obtaining access to the health care system. These differences are especially important in instances of domestic violence. The transient life style of migrant farm workers, combined with geographic and social isolation, make it especially difficult for health care providers to meet the needs of migrant battered women. Strategies for working with migrant battered women are offered. PMID- 8369774 TI - Nursing care of rural battered women. AB - Rural battered women face enormous challenges when they attempt to end the abuse in their lives. Success depends on overcoming difficulties such as geographic isolation from sources of help; lack of accessible services for battered women and their children; limited opportunities for higher education, employment, and affordable housing for women; and strong allegiance to the land, kinship ties, and traditional gender roles. Through community education, routine assessment for abuse, responding in a helpful manner to women who disclose abuse, and forming links with existing programs for battered women and their children, nurses in rural areas can positively influence the health and safety of rural battered women. PMID- 8369775 TI - Changing women's lives: the primary prevention of violence against women. AB - Significant numbers of women in the United States experience violence and abuse in their intimate relationships that compromise the health and safety of the women and their children. This article discusses the problem of violence against women and outlines strategies for responding to violence and abuse in the primary care setting. Nurses can play a vital role in the primary prevention of abuse by implementing abuse screening and education on the issue of violence against women. This article presents strategies for the primary prevention of abuse and guidelines for mobilizing support for women. Collective prevention strategies aimed at eliminating violence against women at the institutional, community, professional, and political level are highlighted. PMID- 8369776 TI - Helping battered women take care of their children. AB - Children of battered women are at risk for a variety of emotional, cognitive, and behavioral difficulties. However, a growing body of research has described the important mediating effects on children of even one positive relationship with a significant person. Nurses need to be aware of family violence and to assess every client and family for this problem. Early identification and interventions can stem detrimental effects and help mothers and children recover. PMID- 8369777 TI - Developing hospital-based domestic violence programs, protocols, policies, and procedures. AB - Interest in developing hospital-based domestic violence programs, protocols, policies, and procedures is growing secondary to efforts by national nursing, medical, and hospital accreditation organizations. Creating specialized health services for domestic violence survivors can be expedited by reviewing existing protocols, policies, and procedures. A reference list of sample domestic violence protocols and a sample domestic violence policy and procedure are provided. The authors share their experiences in developing two of the nation's eight hospital based domestic violence programs. Domestic violence is a nursing concern, and nurses have been the leaders in providing perinatal and women's health services to battered women. Implementing the suggestions contained in this article will enhance hospitals' successful compliance with the 1992 Joint Commission on Accreditation of Healthcare Organizations guidelines for emergency and ambulatory services departments. The need for preprogram data collection, multidisciplinary support, patient and staff safety, specific program services, and staff supervision is addressed. PMID- 8369778 TI - Woman abuse: educational strategies to change nursing practice. AB - Nurses and other health care providers are ideal persons to intervene with women who are experiencing violence and abuse in their intimate relationships. All women are not assessed for this health care problem because of lack of education on the part of their health care providers. This article presents principles and methods for the provision of education about women abuse to practicing nurses and students in graduate and undergraduate nursing programs. By redressing this lack of knowledge and skills, nurses will be empowered to provide clinical intervention and leadership in addressing this major health and social problems. Sample outlines and objectives are provided. PMID- 8369779 TI - Domestic violence: ethical issues in the health care system. AB - Domestic violence is a highly prevalent event in the United States. Health providers frequently treat abused patients; however, many do not routinely assess for family violence or suspect it when the injuries seem fairly obvious. Because abused women feel stigmatized by the violence, they are hesitant to volunteer the abuse. In 1990, the Joint Commission on the Accreditation of Healthcare Organizations added requirements for emergency and ambulatory care services to develop and use protocols for the identification of violence among patients. This article addresses the ethical and legal dilemmas facing nurses that influence their assessment and intervention in family violence. PMID- 8369780 TI - Woman abuse and public policy: potential for nursing action. AB - Woman abuse is the number one cause of trauma to women in the United States and a leading cause of women's mortality and morbidity. Nursing has been in the forefront in conducting research, identifying survivors, and intervening with women abuse in a variety of health care settings. Several initiatives are being taken by the American health care system with regard to this problem. Nurses, especially those in maternal, child, and women's health care arenas, need to continue their leadership in and support for these policy measures. PMID- 8369781 TI - TB control in the 21st century. PMID- 8369782 TI - The impact of education on treatment compliance. PMID- 8369783 TI - Respiratory function in precapillary pulmonary hypertension. AB - Since dyspnoea on exertion is very often the first symptom of precapillary pulmonary hypertension (PPH), either from chronic thromboembolic pulmonary hypertension (CTEPH) or from idiopathic pulmonary hypertension (IPH), these patients are often first examined in a pulmonary function laboratory. We carried out a retrospective study (1987-1992) on pulmonary function in 34 patients diagnosed to have PPH by means of specific diagnostic tools, out of 5,467 patients first attending our laboratory. Nine suffered from IPH, 10 from CTEPH and 15 from Eisenmenger physiology. This last group differed from the others, since its diagnosis had been known for a long time and the stage of the disease was more advanced, when pulmonary function tests were performed in our laboratory (with a view to transplantation). Respiratory function, blood gases and arterial oxyhaemoglobin saturation (HbSaO2) during exercise (Bruce protocol), diffusing capacity of the lungs for carbon monoxide (DLCO), shunt fraction (QS%) (approximation obtained from arterial oxygen tension (PaO2) after 100% oxygen breathing) had been evaluated. In the first two groups, in contrast to other reports, we could observe no obstructive defect. Only 20% of the subjects had restrictive defects, however mild. The typical functional picture of these patients revealed normal lung volumes, normal or slightly reduced DLCO, mild hypoxaemia with hypocapnia, severe HbSaO2 drops during exercise, and pathological QS%. We conclude that every time a patient presents with breathlessness at rest or on exercise, a normal chest X-ray and respiratory function tests, pulmonary hypertension must be suspected and subject to specific and invasive tests. More severe functional impairment was observed in the PPH from the Eisenmenger disorder. This might be due to a more advanced stage of this type of hypertension at the time of our observation and/or to the different mechanisms of the diseases themselves. PMID- 8369784 TI - Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy. AB - A study was carried out in six human volunteers, to assess the blood kinetics of isoniazid, rifampicin and pyrazinamide, administered in a fixed-triple combination intended for use in intermittent chemotherapy of tuberculosis. The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide. In each subject, the same dose of each drug was administered individually in separate sessions and the results compared. The results indicated that, at the level of dose of the intermittent tablet, no negative interactions between the drugs were observed. PMID- 8369785 TI - Tracheobronchopathia osteochondroplastica. AB - A 65 year old man presented with exacerbation of the chronic bronchitis from which he had been suffering for several years. A chest X-ray revealed disatelectatic pulmonary zones. Bronchoscopy showed numerous nodules, beginning at the mid-trachea and extending into the major bronchi. Histological examination of the biopsy specimens demonstrated well-differentiated cartilaginous tissue, consistent with tracheobronchopathia osteochondroplastica. PMID- 8369786 TI - The assessment of respiratory function in a patient with dyspnoea and severe hypoxaemia. AB - In the investigation of dyspnoea and severe hypoxaemia the clinical relevance of multiple diagnostic techniques was studied. The patient was sequentially studied utilizing several techniques. The degree of lung impairment by spirometry, diffusing capacity for carbon monoxide, haemodynamics, pulmonary gas exchange, ventilation-perfusion relationships assessed by the multiple inert gases elimination techniques, ventilation and perfusion lung scans, gallium 67 scintigraphy, bronchoalveolar lavage and high resolution computerized tomography, twice over a period of 12 months during recovery under treatment. A marked impairment of pulmonary gas exchange was first explained by diffusion impairment and ventilation-perfusion mismatch. The multiple inert gas elimination technique allowed determination of the cause of hypoxaemia by ventilation-perfusion inequality. A pathological correlate of the ventilation-perfusion inequality was the appearance of honeycomb lungs detected by high resolution computed tomograph and active alveolitis by bronchoalveolar lavage. All results were consistent with a diagnosis of fibrosing alveolitis. The patient was evaluated again during treatment. Some functional improvement occurred despite persistence of the same pathological findings. In conclusion, this study demonstrates the value of information derived from different tests. Physiological correlations complemented by pathological observations expand understanding of the pathogenesis of disease. These procedures contribute to understanding mechanisms responsible for functional impairment. PMID- 8369787 TI - Diagnosis of pulmonary problems in HIV-infected patients. AB - During the past 13 yrs it has become evident that pulmonary complications occur frequently and are often life-threatening in patients infected with the human immunodeficiency virus (HIV). Moreover, the spectrum of HIV-related pulmonary diseases has enlarged considerably and it now includes numerous infectious and non-infectious conditions. Because clinical and radiological presentation is generally nonspecific and often altered by diminished signs of inflammation or prophylactic measures, and multiple simultaneous complications frequently occur, an early aetiological diagnosis is essential. The diagnostic work-up of these patients must be straightforward. Examination of (induced) sputum and bronchoalveolar lavage fluid are the most important procedures. If they are not diagnostic, transbronchial biopsy, transbronchial needle aspiration, computed tomography and echocardiography are most often revealing. However, we must be continuously prepared to face new complications in the course of this devastating disease. PMID- 8369788 TI - Pulmonary lymphangioleiomyomatosis. AB - Lymphangioleiomyomatosis (LAM) is an interstitial lung disease seen virtually only in women of childbearing age. The diagnosis, symptoms, paraclinical investigations including the use of CT and spirometry are reviewed. A hormonal dependency of LAM seems obvious, but the exact mechanism has never been understood. Oestrogen and Progesterone receptors may or may not be present in the myoma tissue in LAM. The receptor status seems to have no influence on the results of treatment with medroxyprogesterone or oophorectomy. In spite of the uncertain results of hormonal treatment a therapeutic trial with medroxyprogesterone 200 mg i.m. weekly is warranted. If no improvement is observed bilateral oophorectomy is recommended. Death due to respiratory insufficiency is common, but prognosis seems better than previously though, survivors for more than 20 years after diagnosis being described. PMID- 8369789 TI - Current issues in the assessment of interstitial lung disease. AB - Interstitial lung diseases (ILDs) are chronic disorders of the lower respiratory tract, characterized by inflammation and derangement of the alveolar walls. The major functional consequence is the loss of alveolar capillary units and, thus, a limitation of oxygen transfer from air to blood. In recent years, new insights into many aspects of alveolitis as the basic pathological substrate of these diseases, the different inflammatory and immune competent effector cells and their role in the mechanisms of injury and repair have changed our concepts about the pathogenesis of ILD. New techniques, such as bronchoalveolar lavage and computed tomography, allow a better assessment of disease activity and extent of the underlying process. This review also discusses the problems of classification of ILD, and concentrates on issues of assessment and markers of disease activity. Treatment is not a topic of this review but better assessment of these disorders is probably a prerequisite of further progress in treatment and prognosis. PMID- 8369790 TI - Bronchoalveolar lavage and the study of proteinases and antiproteinases in the pathogenesis of chronic obstructive lung disease. AB - Bronchoalveolar lavage has been used for 15 yrs to investigate the role of proteinases and antiproteinases in the pathogenesis of emphysema, but the results are confused by numerous technical factors, many of which may prove insurmountable. Even if the problems can be overcome, the technique will probably not prove sensitive enough to provide a true insight into the pathogenesis of emphysema in man. Nevertheless, the studies with this technique have provided important information and methodologies that have advanced our scientific, if not pathological, knowledge. Perhaps further applications of the knowledge obtained, to cellular and genetic studies, will eventually establish the true mechanisms involved in determining whether a smoker remains "healthy" or develops disabling disease. Lavage may have played a major role in the study of emphysema, if for no other reasons than to establish the fact that the pathogenesis of the disease is far from clear. PMID- 8369791 TI - Treatment of nocturnal asthma. AB - Cough, wheeze and breathlessness at night are common problems for many asthmatics and result from airway narrowing. Therapy should consist of improving management of their asthma over the full 24 h day by use of inhaled steroids and conventional inhaled bronchodilators. Such therapy should be introduced before treatment specifically improving nocturnal airway calibre is introduced. Inhaled long acting beta 2-agonists are the current long acting bronchodilator of choice in such patients. PMID- 8369792 TI - The fundamentals of cardiopulmonary exercise testing. PMID- 8369793 TI - A primer in cardiopulmonary exercise testing. AB - Cardiopulmonary exercise testing is useful in diagnosing the cause of exercise intolerance, in evaluating disability, and in defining the response to therapy. This testing modality is firmly founded on physiological principles. An efficient interaction of the body's systems is required to transport oxygen to the exercising muscles; failure of any system will yield characteristic changes in the ventilatory and gas exchange responses to exercise. An important measurement to make during exercise testing is the work rate at which oxygen transport begins to be inadequate. This work rate, known as the anaerobic threshold, is marked by a rise in blood lactate, and can be estimated noninvasively by examination of gas exchange responses during incremental exercise. In recent years, computerized systems and improved transducers have been introduced to facilitate breath-by breath measurements during exercise testing. These systems also facilitate calibration, data presentation and report generation, making cardiopulmonary exercise testing a practical testing modality. PMID- 8369794 TI - Considerations on 200 cases of percutaneous cricothyroidotomy (minitracheotomy). AB - More than 10 yrs ago, minitracheotomy was suggested as an elective method in the treatment of sputum retention, resulting from impaired ability to cough, in many medical and surgical diseases. We report our experience of 200 cases of percutaneous cricothyroidotomy in our Intensive Care Unit (145 patients), and in other wards (55 patients). The results confirm that minitracheotomy is easy and quick to perform, well-accepted by patients, and free of relevant complications when the technique is performed correctly and sufficient care is adopted. About 60-70% of treated patients benefited by minitracheotomy and did not require more invasive interventions. A better control of technique, moreover, allowed other possible applications to be discovered. PMID- 8369795 TI - Passive smoking and children. PMID- 8369796 TI - Fine structural characterization of the olfactory epithelium and its response to divalent cations Cd2+ in the fish Alburnus alburnus (Teleostei, Cyprinidae): a scanning and transmission electron microscopic study. AB - The olfactory organ of the fish Alburnus alburnus consists of 22 lamellae arranged into rosette like structure and are built up by supporting, gland, basal, ciliated and unspecialized epithelial cells, as well as receptor cells with microvillous, ciliated or rod shape dendritic endings. The spatial distribution of the supporting and gland cells can be considered homogeneous while the ciliated epithelial cells are dominant on the latero-marginal areas of the lamellae with a 10 +/- 3/1000 microns 2 average density. The occurrence frequency of the ciliated receptor cells is the highest in the medial area with a 30 +/- 6/1000 microns 2 average density while the microvillous receptor cells have the highest occurrence frequency in the dorso-marginal area of the olfactory lamellae with a 25 +/- 15/1000 microns 2 average density. Rod shape sensory dendrites were detected with a negligible density. The presence of divalent cations Cd2+ in the environment significantly increased the density of rod shape sensory dendrite 19.8 +/- 7.7/1000 microns 2. These results demonstrate that the appearance and composition of the population of sensory dendrites on the olfactory lamellae are affected by environmental factors. PMID- 8369797 TI - Minireview: regulation by second messengers of permeability in the cerebral microvessels. AB - The view that the cerebral endothelial cells represent the cellular analogue of the blood-brain barrier has been generally accepted. The regulation of transport processes operating in the cerebral endothelial cells is of great current interest. Different elements of the intracellular signaling messenger systems have been detected in the course of our studies in the cerebral endothelial cells. Our knowledge of these regulatory mechanisms is briefly reviewed here with special emphasis on the importance of second messenger molecules and phosphorylation of certain proteins of microvascular origin. PMID- 8369798 TI - Spatial selectivity in the anterior ectosylvian visual area of the cat. AB - Pattern reversal visually evoked potentials (PR-VEPs) were recorded in the anterior ectosylvian visual area (AEV) of the cat, and the dependence of the PR VEPs on the spatial frequency (SF) and the mean luminance of the stimulation was studied. Six SFs between 0.025 and 1 cycles per degree (c/d) and four light density levels between 2 x 10(-2) and 117 cd/m2 (candela per square meter) were tested. The latency of the first positive component (P1) and the amplitude measured between P1 and the first negative (N1) component were analyzed. The dependence of the PR-VEP latencies on the SF displayed a significant relationship, with a minimum at around 0.05 c/d. This relationship was consistent at all luminance levels tested. The dependence of the amplitudes on the SF gave a "low-pass" tuning curve at every luminance level. The higher the luminance level, the steeper was the curve. The cut-off SF of these curves was at around 1 c/d under photopic conditions and around 0.6 c/d under scotopic conditions. The contrast dependence of the PR-VEP amplitudes exhibited saturation at 0.5, which was much higher than that of either the striate cortex or other extrastriate visual cortical areas, but similar to that of the superior colliculus. These results provide further evidence in support of the notion of a tecto extrageniculo-extrastriate visual pathway functioning separately from the geniculo-striate mechanisms. PMID- 8369799 TI - Vimentin persists in the mature glia of fish brain. AB - Adult carp brains were processed for immunohistochemical staining against vimentin and glial fibrillary acidic protein. The shape, density and distribution of immunopositive structures were found to be very similar with both types of antibody. Thus, it appears that vimentin, the cytoskeletal protein typical for immature glia in the early phase of ontogenesis in mammals can also be demonstrated in the adult glia of the phylogenetically older fish brain. PMID- 8369800 TI - The astrocytic localization of protein kinase C in the neocortex, hippocampus and in vitro hippocampal slices of the guinea pig. AB - Immunohistochemical studies prove the most of the neurons of the central nervous system express one or more protein kinase C isoenzymes. However, there are only a few descriptions of the glial localization. In the present study, we detected protein kinase C immunohistochemically in guinea pig sensory neocortex, hippocampus and hippocampal slices following in vitro maintenance. Monoclonal antibodies against types II and III of protein kinase C were used. Consecutive sections were stained with polyclonal anti-glial-fibrillary-acidic protein serum. Scattered astrocytes contained protein kinase C in layers I and VI of the cerebral cortex, in the subcortical white matter, the subiculum, alveus and molecular layer of Ammon's horn, in the hilus and molecular layer of the dentate fascia. Ultrastructurally, immunostaining of glial processes in the neuropil and around blood vessels was observed. Strong staining of the endoplasmic reticulum and nuclear envelope was noted in glial cell bodies. The ultrastructural localization of protein kinase C suggests its participation in receptor-mediated processes, which may influence the shape and function of astrocytes. PMID- 8369801 TI - The effects of in vivo selenium supplementation on the amplitude of the spontaneous contractions and the responses to acetylcholine in isolated rabbit ileum. AB - This study was carried out to investigate the effect of selenium supplementation at a therapeutic level on the isolated ileum contractions and the acetylcholine responses in New Zealand rabbits. While no difference with respect to the controls was found in the spontaneous ileum contraction frequencies a significant increase in the contraction amplitude was noted after 15 days of supplementation. Increasing concentrations of acetylcholine in the perfusion solution resulted in a significant increase of the contraction amplitudes in the supplemented animals as compared to controls. The tissue selenium levels and the gluthathione peroxidase activities were also found significantly higher than the controls. No difference was observed between the contraction numbers in the two groups. These findings indicate that selenium supplementation does not influence the smooth muscle resting potential. PMID- 8369802 TI - Appearance of diaminobenzidine-staining glial cells in the rat CNS: an ontogenetic histochemical study. AB - The postnatal appearance of diaminobenzidine (DAB)-staining glial cells was studied in certain regions of the rat central nervous system. DAB-positive cells appeared in the hypothalamus, the nucleus of the solitary tract and the most superficial laminae of the spinal dorsal horn on the 7th, 8th and 14th postnatal day, respectively. The number and staining intensity of these DAB-positive cells progressively increased and reached the adult levels at the end of the third postnatal week. Glial staining is likely to result from a non-enzymatic oxidation of DAB, since it was resistant to heat pretreatment, but was abolished if hydrogen peroxide was omitted from the incubation medium. The present results reveal that a particular population of glial cells exhibit a characteristic developmental change which can be detected by means of peroxidase histochemistry. The close topographical relationship is suggestive of a functional association between capsaicin-sensitive primary afferents and DAB-positive glial cells. PMID- 8369803 TI - Drug-induced systemic lupus erythematosus in childhood. PMID- 8369804 TI - Plasmapheresis in lupus. PMID- 8369805 TI - A review of serological abnormalities in relatives of SLE patients. PMID- 8369806 TI - Antiphosphatidylethanolamine antibodies in systemic lupus erythematosus. AB - Antiphosphatidylethanolamine antibodies (aPEA) were investigated in a population of 78 systemic lupus erythematosus (SLE) patients, by means of an enzyme-linked immunosorbent assay method. These antibodies are specifically directed against phosphatidylethanolamine, one of the zwitterionic phospholipids present in cell membranes. Antiphosphatidylethanolamine antibodies were found in 13 patients (16.6%). They were generally associated with lupus anticoagulant (two patients), antiphospholipid antibodies directed against anionic phospholipids (six patients), or both (four patients). In only one case, aPEA were the sole detectable antiphospholipid antibodies. Thrombosis, recurrent fetal loss, valvular disease or neurological involvement was present in most (11 of 13) of the patients with aPEA. It seems valuable to carry on further searches for these antibodies in SLE, since patients with aPEA are at higher risk of thrombosis and/or recurrent fetal losses than are patients with antiphospholipid antibodies (anticardiolipin, anti-anionic phospholipid and/or lupus anticoagulant) other than aPEA. Moreover, since aPEA can be the sole detectable antiphospholipid antibodies, they should be investigated in SLE with thrombosis when neither lupus anticoagulant nor anticardiolipin antibodies can be demonstrated. PMID- 8369807 TI - Reciprocal changes in complement activity and immune-complex levels during plasma infusion in a C2-deficient SLE patient. AB - Although systemic lupus erythematosus (SLE) is abnormally common in individuals with complement deficiency, conclusive evidence has been lacking for a direct causal relationship between disease manifestations and a missing complement component. A patient with C2 deficiency and SLE has been treated with 56 courses of fresh frozen plasma (FFP) infusions over a period of 8 years. Each infusion, involving a total of 12 units of FFP administered in equal doses over 4 consecutive days, has consistently resulted in a transient restoration of the classical pathway of complement, and a full clinical remission lasting 6-8 weeks. This report is concerned with changes in the levels of immune complexes, C2 and C3d during an infusion cycle. Four progressively rising peaks in C2 and C3d were observed during the 4 days of the plasma infusion, and these peaks coincided with four reciprocally descending troughs in the levels of immune complexes. Identical fluctuations have been consistent in all the plasma-infusion cycles that have so far been monitored, and their consistent association with clinical remissions indicates a causal relationship between the C2 restoration and clinical remissions in this C2-deficient SLE patient. PMID- 8369808 TI - Clinical renal involvement in Afro-Caribbean lupus patients. AB - This study reports the severity of clinical lupus nephritis (LN), defined as the sustained presence of proteinuria and/or cellular casts, in a group of 68 newly diagnosed patients with systemic lupus erythematosus (SLE) in Curacao. Fifty-four patients (78%) developed clinical signs of LN, of whom 31 (54%) had clinical LN at the time of SLE diagnosis. The probability of developing clinical LN reached 80% in the first 3 years after SLE diagnosis and hardly increased later. No clinical or serological differences existed at the time of SLE diagnosis or at onset of LN between patients with early-or late-onset LN. Survival in patients without LN was 100% at 5 years, while for patients with clinical LN these rates at 1 and 5 years were 91% and 59%, respectively (P = 0.0001); male LN patients had a worse prognosis than females (P = 0.012), while time of LN onset did not influence survival. Six patients (11%) developed end-stage renal failure; all were female, five had early LN and one had late-onset LN (P = 0.17). Renal survival was 97% and 80% at 1 and 5 years, with decreased rates for patients with nephrotic-range proteinuria (P = 0.02). Hypertension was present in 13% of LN patients, but had no influence on patient or renal survival. Thus, clinical LN was a frequent complication, which carried a poor prognosis in these Afro Caribbean lupus patients. PMID- 8369809 TI - Clinical diversity of Raynaud's phenomenon in childhood: report of six cases. AB - Six pediatric patients with Raynaud's phenomenon are reported. Three patients had clinical and immunological evidence for a connective tissue disease; one had primary Raynaud's phenomenon associated with antinuclear antibodies and two had Raynaud's phenomenon secondary to exposure to lead and to a vibrating instrument, respectively. The diagnostic and therapeutic implications of these observations will be discussed. PMID- 8369810 TI - Allergic disorders in systemic lupus erythematosus. AB - Allergic disorders commonly occur in patients with systemic lupus erythematosus (SLE) and allergies to some drugs may occasionally be related to disease flares. We evaluated the prevalence of several types of allergy in 132 patients with SLE and their families and compared the SLE patients with a control group of 66 patients with non-lupus disorders. Total IgE levels were tested in 117 SLE patients and 61 controls. Eighty-three of the 132 SLE patients (63%) had a history of at least one type of allergic disorder. This prevalence was significantly higher (P < 0.0001) than that of the control group (20 of 66 controls). The prevalence of drug allergy (38% vs. 17%; P < 0.005), skin allergy (36% vs. 17%; P < 0.01) and insect allergy (14% vs. 2%; P < 0.02) were significantly higher in SLE patients when compared with controls. Family members of SLE patients had an increased prevalence of at least one type of allergy (55% vs. 24%; P < 0.0001), allergic rhinitis (30% vs. 14%; P < 0.02), asthma (25% vs. 9% P < 0.02), and both rhinitis or asthma (44% vs. 20%; P < or = 0.002). The presence of allergy both in the patient and in the family was more frequent in SLE patients than controls (42% vs. 15%; P < 0.001). We found no differences in total IgE levels between the two groups. Drug, skin and insect allergies were particularly frequent in SLE patients. We also found a high prevalence of rhinitis and asthma in their families. PMID- 8369811 TI - Drug-induced systemic lupus erythematosus in a nine-year-old boy. AB - After a series of intercurrent infections, a 9-year-old boy on ethosuximide for pefit mal developed typical drug-induced systemic lupus erythematosus. After ethosuximide was stopped, he continued to deteriorate and was treated with corticosteroid therapy, which could be only gradually tapered off over many months. Follow-up 4 years later showed him to be completely well. PMID- 8369812 TI - Factitious systemic lupus erythematosus. AB - We report the case of a 15-year-old girl who simulated a complex clinical picture including cutaneous lesions, fever, arthralgia, asthenia and oliguria. A diagnosis of probable systemic lupus erythematosus (SLE) was assumed by numerous specialists and steroid therapy instituted. Factitious SLE should be considered for differential diagnosis of SLE, especially when laboratory evidence for autoimmunity is not demonstrated. PMID- 8369813 TI - Parkinson-like symptoms as a manifestation of systemic lupus erythematosus. AB - A 42-year-old Japanese woman with systemic lupus erythematosus (SLE) developed Parkinsonian-like movements. Steroid pulse therapy was most effective and additional anti-Parkinsonian drugs were not required. Although psychosis, seizures and meningitis are common central nervous system (CNS) manifestations in SLE patients, Parkinsonian-like symptoms are extremely rare. The putative genesis and treatment of CNS lupus are discussed. PMID- 8369814 TI - Blood transfusion related HBV and HIV infection in a patient with SLE. AB - We described the course of a young man with SLE who developed hepatitis B virus and human immunodeficiency virus infections through contaminated blood transfusion. He presented with severe SLE, improved on treatment and then developed hepatic failure which responded to conservative treatment. He now has AIDS and the SLE and HBV infection are quiescent. PMID- 8369815 TI - Histiocytic necrotizing lymphadenitis in a sibling of a patient with systemic lupus erythematosus. PMID- 8369816 TI - [Chromosomal analysis of bladder tumors. Technical aspects, anatomoclinical correlations and perspectives. Report of 18 cases]. AB - The course of bladder tumours is difficult to predict. The most reliable prognostic factor at the present time is histological grade. Cytogenetic subclasses of bladder tumours can be distinguished on the basis of the demonstration of karyotype anomalies in bladder tumour cells. Eighteen patients underwent cytogenetic examination of their bladder tumour and were followed for an average of 35 months. Multivariate analysis of the clinical and laboratory parameters studied revealed the importance of age and the absence of trisomy 7 in the tumour on patient survival. The presence of trisomy 7 in a bladder tumour may therefore constitute a factor of poor prognosis. This hypothesis needs to be confirmed by further studies in larger populations. The search for this anomaly can be performed by fluorescent in situ chromosomal hybridisation, a technique which transforms cytogenetics from an experimental procedure into a routine complementary investigation. These techniques can be performed on urine samples, suggesting the possibility of their application to screening or follow-up of bladder tumours. PMID- 8369818 TI - [Hypospadias in the adult: report of 15 cases]. AB - This paper is based on the analysis of 15 cases of adults between the ages of 17 and 72 years with hypospadias, previously untreated in 2 cases and unsuccessfully treated in the other 13 cases. The author demonstrates the severe sexual, psychological and urinary implications of this malformation when it is not correctly treated during childhood. The difficulties accumulate with age and the problems become more and more difficult to treat, especially as these patients are frequently from poor socioeconomic groups. The conclusion of this study is not original, but once again emphasises the need to correct this malformation as early as possible, at least before puberty and with a minimum of operations (one operation whenever possible). PMID- 8369817 TI - [Duckett's+ simple surface or double surface? Comparison of 2 urethroplasty procedures. Report of 91 hypospadias]. AB - The results and complications of the treatment of hypospadias were studied in relation to the two pedicle foreskin mucosal flap techniques described successively by Duckett, "single surface" and "double surface". 91 urethroplasties were performed: 58 "single surface" and 33 "double surface" Duckett urethroplasties. The children were operated between the ages of 18 months and 16 years with a mean age of 4 years. 75% of children had a good result on long-term follow-up. In the case of major complications, essentially fistula, distal necrosis af the urethra or stricture, a single reoperation increased the percentage of good results to almost 98% for the entire series. However, when the two procedures were compared, a good result was obtained immediately in 81% of cases for the "single surface" operation versus 66% for the "double surface" operation. The fistula rate was 27.2% with the "double surface" flap versus 13.7% with the "single surface" flap and the distal stricture rate was 15.1% with the "double surface" flap versus 3.4% with the "single surface" flap. In the light of these results, Duckett's "double surface" procedure has been abandoned in favour of the "single surface" flap. PMID- 8369819 TI - [Posterior vertical lumbar approach in the treatment of pyelo-ureteral junction syndromes in the adult]. AB - Posterior vertical lumbar incision is an alternative incision for the treatment of hydronephrosis due to ureteropelvic junction anomaly in adults. The authors have performed 18 pyeloplasties via this incision in adults between the ages of 19 and 72 years (mean 36 years). The results of pyeloplasty (88% success rate) were comparable to those obtained via other incisions. The operating time varied between 50 and 110 minutes (mean: 75 minutes) and the mean hospital stay was of the order of one week. The morbidity was low and essentially consisted of parietal complications such as hypoaesthesia or hypotonia. The technique is simple to perform provided the contraindications, especially those related to patient anatomy, are respected. PMID- 8369820 TI - [Posterior vertical lumbar incision in the treatment of pyelo-ureteral junction anomaly: report of 71 cases]. AB - Posterior vertical lumbar incision, described for the first time in 1869 by Simon, provides a simple access to the kidney and offers excellent exposure of the ureteropelvic junction. The technical modifications proposed by Gil Vernet facilitate access to the kidney and reduce the morbidity. The operative technique is described in detail and the authors report their retrospective experience of 71 cases of correction of ureteropelvic junction anomalies (stage 2, 3 and 4). The morbidity was low (19%). Patients returned to work by the 3rd week. 88% of good results were observed at 3 months (84% in initial stage and 4 lesions). This approach should be preferred to the lateral incision or the percutaneous approach due to the simplicity of the technique and the low complication rate. PMID- 8369821 TI - [Calculi of the ilio-pelvic ureter: therapeutic approach and importance of ureteroscopy regarding 200 cases]. AB - The authors report their experience of 200 consecutive emergency admissions for iliopelvic uteric stones. 82 patients (41%) eliminated their stones with medical treatment. 118 patients (59%) required ureteroscopic treatment either by immediate basket extraction (n = 58) or by contact fragmentation (pulsed laser = 57, ultrasound = 1, electrohydraulic catheter = 2). 6 failures were observed and one case of distant ureteric stenosis was successfully treated by balloon dilatation. This therapeutic approach cured 187 (93.5%) of the patients of their stones within an average of 8 days (82 "spontaneous", 105 "endourological") with a mean hospital stay of 2.3 days and 2.7 days, respectively. Ureteroscopy had a success rate of 95% and appears to be the most effective treatment, but the medical option remains the basic treatment for stones of the lower ureter. PMID- 8369822 TI - [Ballistic (Lithoclast) and hydro-electric (Riwolith) endo-ureteral lithotripsy. Report of 60 cases]. AB - 25 hydroelectric endoureteric lithotripsies (Group 1, Riwolith) and 35 ballistic endoureteric lithotripsies (Group 2, Lithoclast) were analysed. 60 stones were treated, including 18 pelvic stones (Group 1 : 10, Group 2 : 8), 39 iliolumbar stones (Group 1 : 14, Group 2 : 25), and 3 stones of the ureteropelvic junction (Group 1 : 1, Group 2 : 2). The mean maximal diameter was 9.9 mm (Group 1 : 8.2, Group 2 : 11). Complementary Dormia extraction was performed in 24 cases (Group 1 : 8, Group 2 : 16), 55 double J stents were implanted (Group 1 : 24, Group 2 : 31) and 23 immediate ECL sessions were performed (Group 1 : 8, Group 2 : 15). Overall, 57 good results were recorded, but 3 complete failures of fragmentation and 2 severe ureteric lesions were attributed to hydroelectric lithotripsy. The Lithoclast, much less traumatic, had a greater stone fragmentation potential, but its efficacy on very mobile stones is limited due to its more intense stone propulsion effect. PMID- 8369824 TI - [Atypical renal cysts: report of 31 cases]. AB - In a series of 205 patients operated for renal cyst, 31 cases had a persistent preoperative doubt concerning the benign nature of the cyst after IVU and/or first-line renal ultrasonography or even computed tomography (80% of cases). Histological confirmation based on analysis of the entire cyst wall or the partial nephrectomy specimen revealed cancer in 45% of cases. Computed tomography must therefore be performed routinely in patients with atypical renal cysts. The authors recommend surgical exploration and partial nephrectomy with frozen section examination at slightest doubt. PMID- 8369823 TI - [Scrotal temperature in 258 healthy men, randomly selected from a population of men aged 18 to 23 years old. Statistical analysis, epidemiologic observations, and measurement of the testicular diameters]. AB - Scrotal hyperthermia can induce certain alterations in spermatogenesis. The basal scrotal temperature used to define hyperthermia is usually 33 degrees C. However, no study, conducted according to a strict methodology has validated this mean measurement. We therefore randomly selected 258 men between the ages of 18 and 23 years from a population of 2,000 young French men seen at the National Service Selection Centre in order to measure the scrotal temperature over each testis and in the median raphe in order to determine the mean and median values for these temperatures. For a mean room temperature of 23 +/- 0.5 degrees C with a range of 18 to 31 degrees C, the mean right and left scrotal temperature was 34.2 +/- 0.1 degree C and the mean medioscrotal temperature was 34.4 +/- 0.1 degree C. Scrotal temperature was very significantly correlated to room temperature and its variations. It was therefore impossible to define a normal value for scrotal temperature. Only measurement of scrotal temperature at neutral room temperature, between 21 and 25 degrees C, is able to provide a reference value for scrotal temperature. In this study, the mean scrotal temperature under these conditions was 34.4 +/- 0.2 degree C, i.e. 2.5 degrees C less than body temperature. In the 12.9% of cases with left varicocele, left scrotal temperature was significantly higher than in the absence of varicocele and was also higher than right Scrotal temperature. The authors also determined the dimensions of the testes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369825 TI - [Is the urodynamic assessment of enuresis in young adults justified?]. AB - Primary or secondary nocturnal enuresis in adults (over the age of 15 years) is rare, but is associated with considerable psychosocial repercussions. The aim of this retrospective study was to determine whether urodynamic studies have any predictive value for the efficacy of the treatments proposed in these patients. This study was based on 20 patients (8 females and 12 males) between the ages of 15 and 33 years (mean: 23.75 years), studied between 1982 and 1990 with a mean follow-up of 13.35 months. Enuresis was primary in 12 patients and secondary in 8 patients. 11 patients had already received one or more treatments without success. Patients with clinically obvious neurological disease were excluded from the study. The urodynamic assessment included water cystomanometry, water urethromanometry with a perfused catheter and uroflowmetry. In addition to the investigation of other associated disturbances of micturition, the following complementary investigations were performed: urine culture in every case, IVU and/or cystography (n = 18), cystoscopy (n = 3), renal and vesical ultrasonography (n = 1). The urodynamic assessment was abnormal in 16 out of 20 cases: marked detrusor hyperactivity (n = 15), impaired compliance (n = 6), significant urethral instability (n = 7), isolated premature urge (n = 1). 15 patients presented with diurnal disorders dominated by frequency (n = 13), urgency (n = 9) and urge incontinence (n = 4); detrusor hyperactivity was detected in every case. The abnormalities observed on the urodynamic assessment guided treatment, allowing correction of enuresis in 3/4 of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369826 TI - [Ectopic ureteral orifice into the seminal duct with homolateral renal agenesis: contribution of ultrasonography]. AB - Based on an incidental case of ectopic ureteric orifice in the seminal tract associated with homolateral renal agenesis, the authors demonstrate the value of ultrasonography, particular transrectal, both for diagnosis and follow-up. Digital rectal examination is the key to the diagnosis, combined with ultrasonography and urography. The indications for surgery depend on the clinical symptoms and signs. PMID- 8369827 TI - [Ultrasonographic study of adrenal gland tumors (report of 5 cases)]. AB - The authors study the ultrasound signs of the adrenal gland based on 5 different types of operated adrenal tumours (a lipoma, an adrenal cortical adenoma, a cyst, a corticoadrenaloma, an adrenal metastasis from a renal cell carcinoma). The ultrasonographic morphological criteria of the normal adrenal gland and each type of tumour are recalled and are illustrated by clinical cases. The value of ultrasonography in the investigation of this organ was evaluated in comparison with other imaging techniques. It constitutes a good first-line diagnostic guiding examination, but needs to be completed by other investigations (computed tomography, magnetic resonance imaging, etc.). Ultrasonography can also reveal asymptomatic adrenal tumours ("adrenal incidentalomas") in which the therapeutic decision (surveillance or surgery) must be based on criteria of size and appearance after a complete laboratory and morphological assessment. PMID- 8369828 TI - [Lymphangiomyomatosis: an exceptional cause of chyluria. Report of a case]. AB - A rare case of lymphangiomatosis without pulmonary involvement is reported. The diagnosis was based on the presence of multifocal lesions and histological examination. Retroperitoneal lesions were responsible for chyluria, which was treated surgically. Chyluria is an exceptional complication of this disease, as only 3 such cases have been reported in the literature. The presence of cutaneous signs raises the question of the relations between lymphangiomatosis and Bourneville's tuberous sclerosis. PMID- 8369829 TI - [Transitional tumor of the right kidney with vena cava thrombus. Report of a case]. AB - Transitional cell carcinoma of the kidney with vena caval tumor thrombus is a rarity with 12 cases reported in the literature. We review in this article the elements of the diagnosis and possible treatment modalities. PMID- 8369830 TI - [Antibiotic prophylaxis in surgery. Consensus conference. December 10-11, 1992]. PMID- 8369831 TI - Elizabeth Shire's helping hands. Interview by Jill L. Sherer. PMID- 8369832 TI - Baby boomers grow up. AB - "The baby boom generation has different expectations and a far different background than older generations" when it comes to their health care, says one expert on the subject. Indeed, providers can expect the demands of the emerging consumer generation to be radically different: The new health care consumers will actively participate in their own care, and will help shape the debate over comprehensive health care reform. Are you ready? PMID- 8369833 TI - Consumers and health reform. Survey highlights awareness gap. PMID- 8369834 TI - Keeping pace. Academic medical centers begin retooling for the future. PMID- 8369835 TI - The long march toward progress. PMID- 8369836 TI - Chain reaction. Will reform hurt hospital-dominated local economies? PMID- 8369837 TI - Birmingham, Alabama. Hospitals, employers forge cost/quality partnerships. PMID- 8369838 TI - Data watch. Study: rural elders living alone at greater risk for health problems. PMID- 8369839 TI - Iowa study helps consumers, employers evaluate health plans. PMID- 8369840 TI - Nine New Jersey hospitals charge Blue Cross with antitrust. Beth Israel Hospital et al. v. Blue Cross and Blue Shield of New Jersey, Inc. PMID- 8369841 TI - LINC (Ladders In Nursing Careers) program helps valued employees pursue nursing careers. PMID- 8369842 TI - 10 steps to protecting your tax-exempt status now. PMID- 8369843 TI - Burnout. PMID- 8369844 TI - Safe motherhood. PMID- 8369846 TI - The healing art of listening. PMID- 8369845 TI - One intact son. PMID- 8369847 TI - A homeopathic primer for midwives. PMID- 8369848 TI - Wise use, best use. PMID- 8369849 TI - The "art" of midwifery. PMID- 8369850 TI - More thoughts on breech. PMID- 8369851 TI - This is Babylon, Part 2. PMID- 8369853 TI - Midwifery and herbs. PMID- 8369852 TI - An American birth. PMID- 8369855 TI - A Japanese birth. PMID- 8369854 TI - Faith or fear? PMID- 8369856 TI - Natural remedies. PMID- 8369857 TI - A matter of choice. PMID- 8369858 TI - Red flags. PMID- 8369859 TI - Java jive. PMID- 8369860 TI - Purslane. PMID- 8369861 TI - Reportability of incidents. PMID- 8369863 TI - Strategic planning in clinical engineering. PMID- 8369862 TI - Medical technology in perspective. PMID- 8369864 TI - Evolution of a successful quality management program for biomedical engineering. PMID- 8369865 TI - An equipment systems laboratory for the biomedical equipment technology curriculum. PMID- 8369866 TI - Three-dimensional visualization of air flow in infant incubators using computational fluid mechanics. AB - An application of three-dimensional (3D) computational fluid mechanics to the air flow in infant incubators is presented. The air flows in two numerical models were simulated by directly solving the Navier-Stokes equations for incompressible gases. The method used was a finite-volume method incorporating a body-fitted coordinate system. The basic model was based on a real infant incubator, which was slightly simplified and included a model of a baby. The number of computation grids was 56 (width) x 21 (depth) x 21 (height) = 24,696. There were several very large-scale eddies in the incubator free space. In addition to the global structure, small-scale eddies were shown to be produced at many locations scattered in the free space. From these results, it is evident that the conventional assumption of steady and uniform flows in incubators is not always justified when considering heat loss from the body of a baby in an incubator. PMID- 8369868 TI - Long-term performance of a rechargeable glucose electrode in vitro. AB - A rechargeable glucose sensor now under development performed satisfactorily for over eight months at 25 degrees C and over 90 days at 37 degrees C without recharging. A prototype sensor was operated through three recharge cycles, which increased the life of the sensor more than two months. This demonstrates the potential for reducing the frequency of surgical replacements. Earlier work utilized three forms of carbon upon which glucose oxidase was immobilized. Recent work reported herein demonstrates that the longer-performing sensor is realized with ultra-low-temperature isotropic (ULTI) carbon powder. Due to its fine particle size, the ULTI carbon with immobilized enzyme acts as a liquid suspension. The sensor is stable and there is no detectable degradation of the sensor components from one recharge cycle to the next. PMID- 8369867 TI - Electrohysterography during pregnancy: preliminary report. AB - The purpose of this study was to test the ability of uterine electrical activity recorded by electrohysterography (EHG) from abdominal electrodes during pregnancy to provide reliable information about uterine contractions. In this preliminary study, abdominal EHG was used to monitor the uterine contractions of eight women, three of whom were having spontaneous contractions related to preterm labor and five of whom were having medical abortions after intrauterine fetal death. The EHG signal consisting of one electrical burst (EB) correlated with a single episode of mechanical activity (MA) in more than 66% of the recorded contractions. When mechanical or electrical activity identified as artifactual was excluded, the temporal correlation of EBs with MA was found in 89% of the recorded contractions. Furthermore, the electrical bursts detected had temporal and spectral characteristics similar to those described previously. Reliable detection of mechanical activity during early pregnancy remains problematic. Nevertheless, abdominal EHG appears suitable for noninvasive monitoring of pregnancies at risk. Further studies are needed to elucidate the significance of the EHG signal in both normal and abnormal pregnancies. It may eventually be possible to use EHG as an ambulatory monitoring tool for the early diagnosis of preterm labor. PMID- 8369869 TI - FDA's international standards policy. PMID- 8369870 TI - Kidney anatomy and physiology. PMID- 8369871 TI - Upper airway obstruction in the syndromal craniosynostoses. AB - This series of consecutive cases details the prevalence and management of upper airway obstruction in the syndromal craniosynostoses (Crouzon, Apert and Pfeiffer syndromes). Upper airway obstruction presents more frequently in Crouzon and Pfeiffer syndrome when presenting early and during the intermediate years. Those patients with Apert syndrome appear relatively free of this problem. Management has been directed toward increasing the size of the nasopharyngeal space by soft tissue alterations (uvulopalatopharyngoplasty, soft palatal split and adenotonsillectomy) with success. Le Fort III advancement osteotomy has been reserved for those more extreme cases, again with objective airway improvement. These techniques have removed the necessity for the progression to tracheostomy in these cases. PMID- 8369872 TI - A preliminary report on open tip rhinoplasty at the time of lip repair in unilateral cleft lip and palate: the Alor Setar experience. AB - A method of open-tip rhinoplasty using nostril and columella rim incisions at the time of unilateral cleft lip repair is described. This preliminary report details experience gained using this technique in the Malaysian centre of Alor Setar following its introduction in September, 1991. PMID- 8369873 TI - Refinements in the axial frontonasal flap. AB - The frontonasal flap is a useful flap for medial and lateral tip defects of the nose. It can be used as a random rotation flap or as an axial flap. This paper describes modifications to the original designs of these flaps, with improvements in the final scar. PMID- 8369874 TI - The cervicopectoral rotation flap--a valuable technique for facial reconstruction. AB - Four cases of lower cheek reconstruction using the cervicopectoral rotation advancement flap are reported. This fasciocutaneous flap can be raised quickly, provides excellent colour and texture match for the tissues of the face, and donor site morbidity is minimal. It is an especially useful method for lower cheek reconstruction following wide excision of melanomas of the cheek and for advanced parotid tumours where skin replacement is required following resection. PMID- 8369875 TI - Observations on experimental flow-through venous flaps. AB - The aim of this work was to compare the survival of an arteriovenous island flap with the survival of an island flap with a flow-through venous supply. Our experimental studies were performed on 95 Wistar rats randomised into six groups: Group 1: Indian ink injection of flow-through venous flaps with capillary network; Group 2: control group deprived of vascularisation; Group 3: control group with arteriovenous supply; Group 4: flow-through venous flaps of group 1; Group 5: epigastric flow-through venous flaps with a main venous trunk; Group 6: histological examination of flow-through venous flaps. The survival of flaps was monitored by direct examination, histological examination, capillaroscopy, and laser Doppler. Three out of 50 flow-through venous flaps survived. There was a statistically significant difference in the delay of clinical necrosis between the composite non vascularised free grafts (2.8 +/- 1.2 days) and the flow through venous flaps (4.1 +/- 1.3 to 4.9 +/- 1.1 days depending on the type of flap). A 20% decreased venous blood flow was observed in the flow-through venous flaps. PMID- 8369876 TI - Restoration of basement membrane structure in pigs following keratinocyte autografting. AB - The attachment of grafts of keratinocyte sheets is mediated in part by the presence and organisation of basement membrane components. The reappearance of basement membrane following keratinocyte autografting was examined in pigs. These studies showed that there was rapid expression of anchoring fibrils and hemidesmosomes, which reached normal numbers at 10 days. However, the length of hemidesmosomes did not reach normal size during the period of study. Weakness of attachment of keratinocyte autografted epidermis was found to lie between the basement membrane and the granulation tissue. This suggests that reported clinical problems with keratinocyte graft attachment may be mediated not only by delay in maturation of the basement membrane but also by its poor integration with collagen of the wound bed. PMID- 8369877 TI - A porcine model using skin graft chambers for studies on cultured keratinocytes. AB - In wound healing research, animal models permit an extensive tissue analysis which is not normally possible in clinical studies. A morphological comparison of human and porcine skin was made in order to identify those aspects of the wound healing process where a porcine model may help our understanding of clinical problems. We describe a porcine model for evaluating the growth of cultured keratinocytes on a variety of wound beds. Polytetrafluoroethylene skin graft chambers were used to isolate wounds and prevent epidermal healing from the skin edge. The chambers remained in situ for 5-7 weeks. We detail the surgical technique, the method of porcine keratinocyte culture and highlight some practical measures that were taken to optimise the "take" of the cultured keratinocyte grafts. PMID- 8369878 TI - Kerato-dermal grafts: the importance of dermis for the in vivo growth of cultured keratinocytes. AB - In a porcine model, we studied the benefit of dermis for the growth of cultured autologous keratinocytes (CAK) on full-thickness wounds isolated within skin graft chambers. Kerato-dermal grafts were prepared in a two stage process using autologous de-epidermalised dermis (DED) and CAK (Group 1). Control wounds were prepared by grafting either CAK only (Group 2) or DED only (Group 3). The median epidermal cover of 34 wounds in Group 1 was 47% and was significantly greater (p < 0.001) than the epidermal cover of 12 wounds in Group 2 (4%) and 14 wounds in Group 3 (12%). The epidermis in Group 1 was durable whereas it was fragile in the control wounds. Histologically rete ridges were present at 2 weeks in Group 1, but not in the control wounds. These data indicate that a dermal wound bed significantly improves the in vivo growth of cultured keratinocytes. PMID- 8369879 TI - Experimental study on growth of epiphysial plate: free graft in rabbits. AB - The growth potential of a free graft of an epiphysial plate was investigated in rabbits. Two epiphysial plate grafts were harvested from each iliac crest. One was grafted to the head (onto bone) and the other to the ear (onto cartilage). Both of the epiphysial plates enlarged to a maximum height of 1.4 cm and became similar to iliac crests. Enchondral ossification was observed up till approximately 28 weeks of age. We conclude that an epiphysial plate has growth potential after free heterotopic transplantation. PMID- 8369880 TI - Histologic examination of peripheral nerves elongated by tissue expanders. AB - Histological changes induced by the slow stretch of peripheral nerves using a tissue expander were studied using a rat sciatic model. Tissue expanders were adapted to elongate the sciatic nerve in vivo. Nerves elongated over an eight week period using this method achieved an average increase in length of 88%. Light microscopic examination revealed that individual axons were separated but each axon and the myelin sheaths were stained well. Electron microscopic examination showed that the convoluted contour of the axons appeared and some loss of myelin was also observed, but the intraneural cytoskeleton elements were kept intact. PMID- 8369881 TI - The effect of omental wrapping on nerve graft regeneration. AB - We have performed 1 cm long nerve grafts in the sciatic nerves of 60 Wistar rats. In 30 cases (n = 30) the grafts were wrapped in omentum. We have studied the nerve regeneration accomplished after 30 and 90 postoperative days from the histological and neurophysiological points of views. Survival of the omentum has been excellent. The histological assessment showed a higher blood vessel population as well as a higher count of axons in the cases where the nerve graft was wrapped in omentum. Areas with neural fibrosis, which are a sign of poor vascularisation, were smaller in the cases with omentum. The amplitude of the contraction in the gastrocnemius muscle was higher in the cases where omentum was used. The endothelial cells of the omentum synthesis fibroblast growth factors (acid and basic) which, due to their angiogenic and neuronotrophic properties, may be the cause of the beneficial effects of omentum on peripheral nerve regeneration. PMID- 8369882 TI - The results of pharyngoplasty by muscle transplantation in "failed cleft palate" cases, with special reference to the influence of the pharynx on voice production. 1953. PMID- 8369883 TI - The results of pharyngoplasty by muscle transplantation by Wilfred Hynes. PMID- 8369884 TI - A severe case of Beare-Stevenson syndrome and associated congenital deformities. AB - A severe case of congenital anomalies is described, with several characteristics of Beare-Stevenson syndrome, such as cutis gyrata, acanthosis nigricans, craniofacial anomalies, ear defects, enlarged umbilical stump and anogenital anomalies. He does not have craniosynostosis or clover leaf skull, which has also been described in this syndrome. This patient also shows hands and feet anomalies, absence of skin adnexa in several locations and dental anomalies, which could suggest an associated ectodermal dysplasia. PMID- 8369885 TI - TB or not TB?: That is the question. PMID- 8369886 TI - The way forward for hydrotherapy. PMID- 8369887 TI - Viscosity of plasma and blood in rheumatoid arthritis. AB - Blood rheology was studied in 130 consecutive RA outpatients, 33 with and 97 without extra-articular disease (EAD), and compared with that in 88 blood donors. All rheological variables were significantly elevated in the RA patients compared with the controls. Painful joint count (PJC), morning stiffness (MS) and radiographic changes (RC) correlated significantly with plasma viscosity (PV), CRP, ESR and fibrinogen concentration (FC), but only in the group without EAD. Corrected blood viscosity (CBV) at a shear rate of 92/s correlated significantly only with MS. Multiple regression with PJC, MS and RC as dependent variables showed significant associations of PJC with PV, MS and CRP and RC with PV. Multiple regression with PV as the dependent variable showed significant associations with FC and IgG. RA patients with EAD had higher PV (P < 0.01), CBV at 92/s (P < 0.05) and ESR (P < 0.05) than the RA patients without EAD. Differences in profiles of viscosity variables between subgroups of EAD in RA patients were observed. PMID- 8369888 TI - Transient decrease in osteocalcin and markers of type 1 collagen turnover during high-dose corticosteroid pulse therapy in rheumatoid arthritis. AB - The effect of corticosteroid pulse therapy on bone metabolism was studied in 10 patients with active RA. We measured alkaline phosphatase, osteocalcin and two recently introduced markers of collagen type 1 metabolism, reflecting synthesis (PICP) and degradation (ICTP). The day after the pulse therapy, there was a statistically significant (P < 0.05) decrease in osteocalcin, PICP and ICTP from the value at start. Three weeks after pulse therapy, these values had returned to baseline. During pulse treatment there is a transient decrease in bone formation, as shown by the changes in osteocalcin and PICP. Because of the changes in ICTP, we conclude that bone resorption is transiently reduced as well, but whether these changes result from a direct or an indirect effect on bone is not clear. ICTP has to be investigated further as a (serum) marker of bone resorption. PMID- 8369889 TI - Tendon calcifications of the hip adductors in chondrocalcinosis: a radiological study of 75 patients. AB - Studies on tendon involvement in articular chondrocalcinosis (ACC) are scarce, with little data focusing on its prevalence and characteristics. We carried out a radiological survey on 75 patients with ACC in order to establish the frequency and radiological appearance of calcific deposits at the origin of the adductor tendons on the ischium. In 19 of these patients, radiological visible linear calcifications compatible with chondrocalcinosis were observed at this site. There is a high correlation between the existence of pelvic tendon calcifications and the extension and intensity of calcific deposits in other articular areas. Calcifications of the adductor tendons are not uncommon in ACC, the amount of calcium pyrophosphate deposits may be the most important factor leading to tendon involvement in this disorder. PMID- 8369890 TI - HLA associations in subjects with rheumatoid arthritis and bronchiectasis but not with other pulmonary complications of rheumatoid disease. AB - We have examined HLA-DR, DQA and DQB variants in 72 controls, 153 subjects with RA without extra-articular features and in subjects with the rheumatoid pulmonary complications of interstitial fibrosis (23) peripheral airways disease (13) and in 41 subjects with RA and bronchiectasis. Subjects with RA alone showed the expected association with HLA-DR4 (79%) but those with RA and co-existent pulmonary fibrosis were less likely to be DR4 positive (61%). No other HLA-DR variants were significantly increased in the different disease groups. HLA DQB1*0501 which types serologically as DQw1 was increased in subjects with RA and peripheral airways disease as compared to rheumatoid subjects with normal lung function, but these differences were not statistically significant. DQB1*0601 was increased in subjects with bronchiectasis with or without RA (but only significantly so in RA-BR subjects) DQB1*0301, DQB1*0201 and DQA1*0501 frequencies were also increased in subjects with RA and bronchiectasis as compared to those with RA alone. PMID- 8369892 TI - Home exercises are as effective as outpatient hydrotherapy for osteoarthritis of the hip. AB - Hydrotherapy for OA of the hip has rarely been evaluated in controlled studies. Forty-seven patients with OA of the hip were followed for 18 weeks. Patients were randomly allocated either to a regimen of home exercises or to twice weekly hydrotherapy for 6 weeks in addition to home exercises. There was an improvement seen in both subjective and objective measures in both groups with treatment. There was no significant difference between the two groups. Response to treatment appeared independent of age, sex and radiological severity. We conclude that for most patients, a carefully graded and supervised regimen of home exercises is beneficial and there is little benefit in adding hydrotherapy to this regimen. PMID- 8369891 TI - Transition questions to assess outcomes in rheumatoid arthritis. AB - The importance of patient-based assessments of outcomes of care in RA is increasingly recognized. There are a number of methods of gaining such data. One method is to request patients to assess change in health status by means of transition questions. This is considered advantageous to other methods because is directly addresses perceptions of change over time and is short and simple. One hundred patients with RA completed a range of clinical, laboratory and health status assessments on two occasions 3 months apart. On the second occasion they also completed a transition question. Results show the question to be valid and to correlate with a number of different changes obtained from assessments. Psychological mood did not appear to influence transition judgements. A small minority of patients experienced changes for specific dimensions of health status in the opposite direction of the transition item. Transition judgements may have an important role in evaluation studies and audit. PMID- 8369893 TI - Glucocorticoids in rheumatoid arthritis--mediators and mechanisms. PMID- 8369894 TI - Benign synovitis of the hip in adults. AB - Hip synovitis plays a part in many rheumatic diseases. In the young adult acute arthritis may be due to reaction to trauma, infection or gout. Although transient synovitis of the hip is a well-known phenomena in children the condition is not well-documented in adults. We present 10 young adults with idiopathic transient synovitis of hip who had attended the Soroka Medical Centre between 1986 and 1990. PMID- 8369895 TI - Letter from Hungary. PMID- 8369896 TI - The diagnosis of Poncet's disease. AB - Two cases of polyarthritis in young people with extra-articular tuberculosis are described. The clinical features were consistent with the concept of Poncet's disease. After synovial biopsy one patient proved to have tuberculous peripheral arthritis. This observation raised doubts about the diagnosis in the other patient. Multiple joints may be simultaneously infected with Mycobacterium tuberculosis and Poncet's disease, if it exists, should not be entertained in the absence of synovial biopsy. PMID- 8369897 TI - Remission of severe rheumatoid arthritis following liver transplantation. AB - We present the case of a 32-year-old male who suffered from severe RA from the age of 21 years. After 9 years of active disease and poor response to therapy the patient developed severe hepatitis induced by the NSAID pirprofen. He went into fulminant hepatic failure necessitating emergency liver transplantation. Liver transplantation was followed by clinical and laboratory remission of his RA and he has remained virtually asymptomatic for more than 3.5 years. The possibility that this favourable clinical course was due to the immunosuppressive effect of the liver transplant rather than the ensuing immunosuppressive therapy is discussed. PMID- 8369898 TI - A case of steroid-responsive organizing pneumonia in a patient with rheumatoid arthritis showing migratory infiltration and normal glucose levels in pleural effusions. AB - A 59-year-old Japanese man with RA was referred to us with arthralgia and pulmonary infiltration. Chest roentgenogram showed migratory infiltration and pleural effusion, the glucose levels of the pleural fluid were not reduced. Transbronchial lung biopsy showed granulation tissue plugging the alveolar ducts, indicating organizing pneumonia and interstitial inflammation. These pathological findings were identical with those for cryptogenic organizing pneumonitis (COP). There was a good clinical and roentgenographic response and the pleural effusion responded well to corticosteroids. The characteristic migratory infiltration in rheumatoid lung disease responds well to corticosteroids. PMID- 8369899 TI - Iliopsoas bursa presenting as deep vein thrombosis in rheumatoid arthritis. AB - The case of a woman with longstanding rheumatoid arthritis presenting with a deep vein thrombosis of the leg secondary to an enlarged iliopsoas bursa is described. The anatomy, presentation and disease associations are described, and the optimum techniques of imaging and management are discussed. PMID- 8369900 TI - HLA and juvenile psoriatic arthritis. PMID- 8369901 TI - The role of infection in juvenile chronic arthritis. AB - Juvenile chronic arthritis covers a heterogeneous group of arthritides for which there appears to be a genetically determined susceptibility. The exact events which trigger or perpetuate an arthritic disease have yet to be defined. There is circumstantial clinical evidence that JCA can be initiated by environmental factors such as infection, and indirect laboratory evidence that immune responses to infectious agents are associated with ongoing JCA; such immune responses seem particularly vigorous within the joint space. Although the weight of evidence favours the hypothesis that the intra-articular inflammatory process is antigen driven, none of the critical antigens have been identified, and it is still unclear whether they are derived from infectious agents or are true auto antigens. We can however expect progress to be made, since techniques are now available for defining the antigenic specificity and TCR usage of synovial T cell populations, while PCR allows exquisitely sensitive detection of infectious agents deposited in the synovial space. Application of these techniques should lead to an enhanced understanding of whether (or in what circumstances) infectious agents are involved in the pathogenesis of arthritis in children. PMID- 8369902 TI - Evolution of synovial fluid mononuclear cell responses in a HLA B27-positive patient with Yersinia-associated juvenile arthritis. AB - A 15-year-old boy who developed acute arthritis following an episode of urethritis, was found to have agglutinating antibodies (titre 1:320) against Yersinia enterocolitica 0:3. Synovial fluid mononuclear cell (SFMC) proliferative responses to this agent and other antigens were examined on four occasions over the subsequent 40 months. Responses to Yersinia were predominant during the first year, but after 29 months responses to purified protein derivative of Mycobacterium tuberculosis and Salmonella were greater than to Yersinia. Moderate responses to a mycobacterial heat shock protein (HSP65) were present throughout the illness. These results suggest that maximal mononuclear cell proliferative responses may change over time, and raise the possibility that responses which are initially specific for the inciting arthritogenic agent may eventually become more generalized. PMID- 8369903 TI - Infantile myofibromatosis: a cause of severe bone pain in a neonate. AB - A 3-week-old, female infant, developed severe bilateral shoulder pain in association with large, symmetrical, lytic lesions in the proximal humeri. The radiological appearance was suggestive of infantile myofibromatosis and bone biopsy confirmed the diagnosis. She subsequently made a complete recovery. This uncommon condition is infrequently confined to bone and except in the presence of obvious pathological fracture, severe pain has not previously been reported. PMID- 8369904 TI - Abnormal fibrinolysis in chronic low back pain. PMID- 8369905 TI - Hospital treatment for low back pain. PMID- 8369906 TI - Charcot arthropathy as an unusual initial manifestation of diabetes mellitus. PMID- 8369907 TI - The British Journal of Surgery 80th anniversary. PMID- 8369908 TI - Carotid endarterectomy: confidence restored. PMID- 8369909 TI - Recurrent varicose veins: a national problem. PMID- 8369910 TI - Infrainguinal vein graft stenosis. AB - Although knowledge of the biological processes involved in the development of intimal hyperplasia has increased markedly in recent years, the precise aetiology of infrainguinal vein graft stenosis remains undetermined. Current therapy is therefore directed at treatment of the established lesion rather than its prevention. There seems little doubt, however, that recent advances in understanding of the vascular biology of normal and pathological saphenous vein will eventually lead to specific targeted therapy that will allow the prevention of vein graft stenosis. PMID- 8369911 TI - Foot volumetry and duplex ultrasonography after saphenous and subfascial perforating vein ligation for recurrent venous ulceration. AB - Forty-three patients undergoing superficial and perforating vein ligation for recurrent venous ulceration underwent preoperative and postoperative foot volumetry and postoperative duplex ultrasonography. Patients were followed for a median of 66 (range 18-144) months. Of nine patients who developed recurrent ulceration, six had femoral vein incompetence and all had popliteal vein incompetence demonstrated by duplex ultrasonography. Of the 34 patients who remained ulcer-free, five had femoral vein incompetence and a single patient had popliteal vein incompetence on duplex scanning, giving positive predictive values for recurrent ulceration of 55 per cent (femoral vein incompetence) and 90 per cent (popliteal vein incompetence). Patients with saphenofemoral incompetence on late follow-up were also more likely to suffer recurrence. Preoperative foot volumetry with tourniquet occlusion of superficial veins showed that the median expulsion fraction of patients who developed recurrent ulcer during follow-up was 0.8 (range 0.6-2.3) per cent compared with 1.5 (range 0.4-2.9) per cent for those who remained ulcer-free (P = 0.025); the median half-refilling time of patients with recurrent ulcer was 1.5 (range 0.5-5.5) s compared with 5.0 (range 0.5-23.0) s for those without recurrence (P < 0.01). Postoperative foot volumetry showed similar differences. Deep venous incompetence, particularly of the popliteal segment, as demonstrated by duplex ultrasonography and foot volumetry, is a useful predictor of recurrent ulceration after subfascial perforator and superficial venous ligation. PMID- 8369912 TI - Recurrent varicose veins: correlation between preoperative clinical and hand-held Doppler ultrasonographic examination, and anatomical findings at surgery. AB - A consecutive series of 118 patients (148 legs) presenting with recurrent varicose veins underwent preoperative clinical and hand-held Doppler ultrasonographic examination by a single observer. The presence of saphenofemoral, mid-thigh perforator and saphenopopliteal reflux was noted. Ultrasonography markedly improved the accuracy of clinical assessment at all three potential sites of reflux compared with operative findings. Of 71 patients undergoing repeat groin dissection, only 20 (28 per cent) had a tied saphenofemoral junction, 31 (44 per cent) had intact major tributaries and 52 (73 per cent) had an intact long saphenous vein (LSV) in the thigh. There was a positive association between mid-thigh perforator reflux giving rise to recurrent varices and the presence of an intact LSV in the thigh. Of 45 legs with saphenopopliteal reflux, only four had previously undergone saphenopopliteal ligation, suggesting that most short saphenous varicosities had either appeared after or had not been recognized at the time of primary surgery. This study indicates that even an experienced vascular surgeon can have difficulty in assessing the presence or absence of recurrent deep to superficial reflux by means of clinical examination alone and that Doppler ultrasonographic examination is mandatory. Recurrence continues to be associated with persistent or recurrent incompetence at the site of previous inadequate surgery. PMID- 8369913 TI - Intraoperative measurement of vascular graft resistance as a predictor of early outcome. AB - The quality of distal run-off is one of the most important factors influencing the early outcome of femorodistal vein grafting. During femoropopliteal and infrapopliteal bypass, assessment of graft resistance and flow were made using a combination of Doppler flowmeter recordings and measurements of arterial pressure. In a series of 100 reconstructions there were 12 early failures. The mean (95 per cent confidence interval (c.i.)) maximal flow measurement in the group of grafts that failed when anastomosed to the popliteal artery or tibioperoneal trunk was 125 (74-176) ml/min compared with 256 (223-289) ml/min in successful grafts (P = 0.006). The corresponding figures for grafts inserted into a single crural vessel were 99 (72-126) and 165 (137-193) ml/min (P < 0.02). In the group that failed the mean (95 per cent c.i.) resistance after papaverine injection was 1.02 (0.82-1.22) peripheral resistance units (p.r.u.) compared with 0.47 (0.44-0.51) p.r.u. in the successful group (P < 0.001). Using a combination of resistance > 0.9 p.r.u. and capacity loss ratio after papaverine injection < 10 per cent to identify grafts that subsequently failed, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 92, 97, 85, 99 and 97 per cent respectively. These results confirm that haemodynamic measurements can be used at operation to identify a group of patients in whom bypass is likely to fail. PMID- 8369914 TI - Intraoperative thrombolysis in the management of thrombosed popliteal aneurysm. PMID- 8369915 TI - Sutureless circumcision. PMID- 8369916 TI - Non-therapeutic operations for penetrating trauma: early morbidity and mortality. AB - A prospective study was carried out to assess the incidence and type of complications after non-therapeutic operations for penetrating trauma. A total of 372 operations were performed on 368 patients with penetrating injuries to the abdomen (240 procedures), chest (49), neck (48) and extremities (35). There were 46 negative or non-therapeutic operations. The incidence of major complications directly related to anaesthesia or operation in this group of patients was 4 percent (two patients). The operation might have contributed to a further three major complications. The mean hospital stay for patients undergoing uncomplicated non-therapeutic operation was 4.1 days; for those with complications it was 21.2 days. It is concluded that non-therapeutic operations for penetrating trauma carry a significant morbidity rate. A policy of selective conservatism is advocated. PMID- 8369917 TI - Electrocautery of the upper thoracic sympathetic chain: a simplified technique. PMID- 8369918 TI - Screening for breast cancer detects tumours at an earlier biological stage. AB - Between August 1988 and July 1990, 17,678 women in the Gateshead, Sunderland, South Tyneside and Durham districts attended the national breast screening programme. A total of 131 cancers were detected. The morphology of cancers detected by screening was compared with that of tumours in 71 patients presenting clinically in the same period. Screen-detected cancers included a higher proportion of tumours of more favourable histological grade and type, were smaller in size and had less axillary lymph node involvement than those detected clinically. Survival was predicted from the Nottingham Prognostic Index. Patients with screen-detected cancer had an expected survival advantage (95 per cent confidence interval) of 26.5 (12.3-40.6) per cent at 5 years, 26.5 (11.8-41.2) per cent at 10 years and 29.1 (14.5-43.7) per cent at 15 years. This survival advantage in screened patients expected at 5, 10 and 15 years is consistent with the 30 per cent reduction in mortality rate demonstrated in the Health Insurance Plan study and the Swedish two counties trial. PMID- 8369919 TI - Cytodiagnosis of breast disease using a liquid suspension medium. AB - Fine-needle aspiration cytology specimens from 187 breast lesions were processed using conventional slide cytology. Results were compared with those from 201 lesions prepared using a liquid suspension medium (Cytospin) for specimen collection, to assess the clinical utility of each technique. The frequency of diagnostic groups was similar for each method. No significant difference was found in sensitivity (conventional slide cytology 86 per cent versus Cytospin 82 per cent), specificity (72 versus 82 per cent) or diagnostic accuracy (88 versus 91 per cent). The Cytospin technique compares favourably with conventional slide cytology and can be recommended for ease of use in breast cytodiagnosis. PMID- 8369920 TI - Use of silicone implants after wide local excision of the breast. AB - The appearance of the breast after wide local excision for carcinoma may be unsatisfactory. In 59 patients undergoing wide local excision a silicone prosthesis was inserted into the cavity at the time of primary surgery. Assessment of the cosmetic result was performed after 12 months by questionnaire and clinical examination. Four prostheses were removed within 1 year because of infection (two patients), wound breakdown (one) and pain (one). Seven prostheses were subsequently removed because of severe capsular contraction. Capsular contraction was more common in patients who had received radiotherapy. Only 23 patients found the results of the implant acceptable or satisfactory. The immediate use of intramammary implants after wide local excision is currently associated with a poor cosmetic result, and the problem of the distorted breast after such excision requires continued attention. PMID- 8369921 TI - New adjustable knot for securing subcuticular running sutures. PMID- 8369922 TI - Laparoscopic removal of an adrenocortical adenoma. PMID- 8369923 TI - Prospective randomized comparison of teres cardiopexy and Nissen fundoplication in the surgical therapy of gastro-oesophageal reflux disease. AB - Teres cardiopexy was compared with Nissen fundoplication in a prospective randomized study of surgery for gastro-oesophageal reflux disease refractory to medical treatment. Follow-up at 3 months of ten patients undergoing each procedure showed good clinical results and improvement of the mean symptom score in both groups, for cardiopexy from 7.8 to 1.1 (P < 0.01) and for fundoplication from 5.7 to 0.2 (P < 0.01). After 1 year, six of the ten patients undergoing cardiopexy required a second antireflux procedure because of recurrent disease, whereas one reoperation was performed after fundoplication. The mean symptom score after 1 year was higher in patients submitted to cardiopexy than in those receiving fundoplication (3.9 versus 0.3, P < 0.01). The mean endoscopic oesophagitis score after 1 year was no different from preoperative values after cardiopexy (1.9 versus 1.9) but was significantly lower after fundoplication (1.5 versus 0.3, P = 0.01). Ambulatory 24-h pH monitoring showed a significantly higher proportion of total time at pH < 4 after cardiopexy than fundoplication (24.0 versus 3.8 per cent, P < 0.05). Cardiopexy is significantly less effective than fundoplication for the treatment of gastro-oesophageal reflux disease assessed at 1-year follow-up. This study does not support the use of cardiopexy either in conventional or laparoscopic antireflux surgery. PMID- 8369925 TI - Oesophagomyotomy for achalasia: a 22-year experience. AB - To determine the clinical results in achalasia, particularly as regards postoperative gastro-oesophageal reflux, a 22-year personal experience with transthoracic short oesophagomyotomy without an antireflux procedure was analysed. A total of 185 such procedures were performed, of which 179 (97 per cent) were available for analysis. There was an overall improvement rate of 89 per cent over a mean postoperative interval of 9 years. Primary procedures were followed by a 93 per cent rate of improvement. Twenty patients, nine of whom had previously undergone one or more oesophageal operations, were considered as having a poor result. Marked gastro-oesophageal reflux accounted for a poor outcome in nine patients. Although the overall rate of postoperative improvement did not deteriorate significantly with time, the level of improvement did, the proportion of excellent results declining from 54 to 32 per cent (P = 0.02) at 10 20 years after operation. These findings substantiate the view that a short transthoracic oesophagomyotomy without an antireflux procedure provides excellent long-term relief of dysphagia for the patient with oesophageal achalasia and is accompanied by an extremely low risk of serious postoperative gastro-oesophageal reflux. PMID- 8369924 TI - Erythromycin improves emptying of the denervated stomach after oesophagectomy. AB - Oesophagectomy, necessitating vagotomy, is associated with delayed gastric emptying. Cisapride and erythromycin have prokinetic effects and improve emptying of the innervated stomach. Their effect on the denervated stomach following oesophagectomy is unknown. The effect of pyloroplasty, cisapride and erythromycin on the rate of gastric emptying after oesophagectomy was studied using a radiolabelled meal. Oesophagectomy was associated with a marked delay in gastric emptying (56 per cent of the test meal remaining after 4 h) compared with age- and sex-matched normal controls (16 per cent; P < 0.001). Erythromycin improved the rate of gastric emptying to preoperative control values (18 per cent). Cisapride had no significant effect on gastric emptying. After pyloroplasty, 32 per cent of the label remained at 4 h (P = 0.065). The mean(s.e.m.) half-emptying time in patients receiving erythromycin was 94(29) min, which was similar to control values, 55(3) min (P = 0.26). Erythromycin may have a role in the treatment of gastric stasis following oesophagectomy or truncal vagotomy. PMID- 8369926 TI - Pattern and surgical treatment of gastric cancer in Singapore. AB - A personal series of 150 patients with gastric cancer operated on over an 11-year period in Singapore is reviewed. Cancer occurred in the antrum and/or body of the stomach in 117 patients and in the cardia in 33. Gastric tumours were well or moderately differentiated adenocarcinoma in 50 patients and poorly differentiated or signet ring cell carcinoma in 100. Surgical resection was performed on 115 patients, in whom it was palliative in 47. Attempted cure by R2 radical resection was performed in 68 patients: 14 with stage I, 12 with stage II and 42 with stage III disease. There was no operative death in these 68 patients. In 82 patients operated on more than 5 years ago, five patients with carcinoma of the cardia and 28 with cancer of the gastric antrum and/or body underwent curative resection. There were 12 known 5-year survivors among the latter 28 patients; 16 of the 28 had stage III disease, six of whom survived 5 years. These results compare favourably with those of an earlier report from Singapore in which there were no 5-year survivors. The improved results probably accrue from earlier diagnosis and the current policy of radical resection. PMID- 8369927 TI - Prognostic significance of histological type in gastric carcinoma with invasion confined to the stomach wall. AB - Survival was determined after resection for the two main histological types of gastric carcinoma, intestinal (n = 223) and diffuse (n = 170), in 393 patients with pT1 or pT2 tumours. Lymph node metastases were present in 94 patients. The 10-year survival rate was significantly lower for patients with intestinal-type than for those with diffuse-type carcinoma (72 versus 91 per cent, P < 0.005). In patients without nodal involvement, the 10-year survival rate was still lower for those with intestinal-type cancer (70 versus 94 per cent, P < 0.01). Recurrence of carcinoma was more often by haematogenous dissemination in patients with intestinal-type cancer. Although the results of resection for pT1 or pT2 gastric carcinoma can be acceptable, the introduction of adjuvant therapy based on histological findings may be necessary for patients with the intestinal type of cancer to prevent haematogenous spread of carcinoma to the liver. PMID- 8369928 TI - Spontaneous rupture of a normal portal vein causing severe retroperitoneal and intraperitoneal bleeding. PMID- 8369929 TI - Kinetic changes and experimental carcinogenesis after Billroth I and II gastrectomy. AB - To determine the risk of gastric remnant cancer according to the type of surgical reconstruction, the distal two-thirds of the glandular stomach was resected in male Wistar rats, followed by gastroduodenostomy (Billroth I anastomosis) or gastrojejunostomy (Billroth II anastomosis). No carcinogens were given and the animals were killed 50 weeks after operation. No cancers developed in 22 rats undergoing Billroth I gastrectomy, but five of 24 with Billroth II anastomosis had adenocarcinoma (P < 0.05). All carcinomas were confined to the stoma. Animals with Billroth II anastomosis had a more advanced grade of mucosal atrophy at the stoma, with a higher incidence of cystic dilatation, submucosal adenocystic proliferation and pseudopyloric metaplasia (P < 0.05). Cell kinetics in the stomal mucosa after Billroth II gastrectomy showed an increased cell count in the proliferative zone, longer duration of S phase and increased cell cycle time (P < 0.05). These results suggest that Billroth II gastrectomy carries a greater risk of cancer than the Billroth I procedure. PMID- 8369931 TI - Translocation of enteric bacteria in humans. PMID- 8369930 TI - Intraoperative enteroscopy in Crohn's disease. AB - Intraoperative small bowel endoscopy was performed on 33 occasions in 31 patients with Crohn's disease. The extent of mucosal inflammation was compared with that of changes in the external bowel wall: serositis, fat-wrapping and mural thickening. The influence of endoscopic findings on surgical management was evaluated. Mucosal inflammation was generally more extensive than serositis (P < 0.01), but less so than mural thickening (P < 0.001). The extent of fat-wrapping did not differ from that of mucositis. Of 23 patients undergoing reoperation or with fistula or abscess, however, eight had serositis and/or fat-wrapping in bowel segments without mucosal inflammation. Endoscopic findings influenced surgical decisions on 20 of the 33 occasions, limiting planned resection in 14, identifying strictures for repair in one, and deciding against resection in two cases and for extended resection in three. These results suggest that external inflammatory changes are unreliable guides to the extent of intestinal mucositis and requirements for resection in Crohn's disease. By visualizing the mucosa, intraoperative enteroscopy can provide information for more precise surgery, thereby limiting resection. PMID- 8369932 TI - Extended left hepatectomy: technical aspects of an evolving procedure. AB - Lessons learned in an operative experience of 14 patients submitted to extended left hepatectomy for the management of liver tumours are presented. There were no deaths within 30 days of operation. Essential preoperative studies, indications and technical details of the operation are described. The importance of the morphology of the tumour and the influence of the tumour on the technique to be adopted are emphasized. Modifications of technique that allow selection of patients for the procedure, control of venous bleeding, accurate identification of the sectorial portal pedicles within the right liver and definition of the plane of parenchymal transection are addressed. PMID- 8369933 TI - Laparoscopic treatment of a liver hydatid cyst. PMID- 8369934 TI - Biliary stent failure after 42 years. PMID- 8369935 TI - Orthotopic liver transplantation for hepatic complications of Wilson's disease. AB - Thirteen orthotopic liver transplantations were performed in 12 patients for hepatic complications of Wilson's disease between May 1988 and July 1992. Ten patients had fulminant hepatic failure and two chronic liver disease. One patient underwent retransplantation for liver abscess secondary to hepatic artery thrombosis. Nine patients survive at a median follow-up of 18 (range 6-31) months. Three patients have died: two from multiple organ failure and sepsis, one from B cell lymphoma. Postoperative complications included bleeding requiring laparotomy in two patients, renal impairment in five, bacterial septicaemia in three, fungal sepsis in two and acute cellular rejection in six. The nine surviving patients are well with normal liver function test results. PMID- 8369936 TI - Superselective intra-arterial chemotherapy with mitomycin for gallbladder cancer. AB - A group of 27 patients with carcinoma of the gallbladder was treated by superselective intra-arterial chemotherapy with mitomycin between 1981 and 1990. Results were compared with those in 22 historical controls. The overall response rate to intra-arterial chemotherapy was 48 per cent. The median survival time for responders was 34 months and for non-responders 8 months. Survival was significantly related to tumour stage in patients treated by chemotherapy (P < 0.001) and controls (P < 0.01); all patients with tumour extending beyond the serosa died within 4 years. The median survival period after intra-arterial chemotherapy was 14 months, compared with 4 months in controls. The cumulative 5 year survival rates for patients treated by chemotherapy and controls were not significantly different. Cessation of chemotherapy was required in 16 of the 27 patients: in eight because of tumour progression, in seven after toxicity to chemotherapy and in one because of patient refusal. Superselective intra-arterial chemotherapy can be useful for patients with cancer restricted to the gallbladder wall but cannot prevent tumour growth once this has extended beyond the gallbladder serosa. PMID- 8369937 TI - Herniation at the site of cannula insertion after laparoscopic cholecystectomy. PMID- 8369938 TI - Sclerotherapy of the human gallbladder using ethanol and tetracycline hydrochloride. PMID- 8369939 TI - Prophylactic use of cefuroxime in biliary tract surgery: randomized controlled trial of single versus multiple dose in high-risk patients. Galant Trial Study Group. AB - To assess the efficacy of a single-dose short-acting antibiotic in the prevention of septic complications after biliary surgery, a randomized controlled double blind multicentre trial was conducted. One dose of cefuroxime before operation (1.5 g intravenously) was compared with a three-dose regimen of the drug as control (1.5 g before and two doses of 0.75 g after operation). The study group comprised 1004 patients with risk factors for infection, who were followed for 4 6 weeks after surgery. The characteristics of both treatment groups were comparable. No significant difference was found between the one- and three-dose antibiotic regimens in preventing postoperative wound infection: 6.6 versus 6.2 per cent for minor wound infection (P = 0.78) and 4.6 versus 3.8 per cent for major wound infection (P = 0.52). The estimated difference in major wound infection rate between the two groups was 0.8 per cent (95 per cent confidence interval -1.7 to 3.3 per cent). PMID- 8369940 TI - Randomized study of the value of laparoscopy before appendicectomy. AB - Two groups of 30 women with clinical signs of appendicitis were randomized to immediate appendicectomy or diagnostic laparoscopy. In the latter group, appendicectomy was performed if a diagnosis of acute appendicitis was established or if the appendix could not be visualized. Eleven patients undergoing immediate operation had unnecessary appendicectomy, compared with two having laparoscopy. This difference of 30 per cent (95 per cent confidence interval 11-49 per cent) was significant (P = 0.01). There was no significant difference in postoperative morbidity rate in the two groups. Diagnostic laparoscopy is a useful preliminary investigation in women with clinical signs of acute appendicitis. PMID- 8369941 TI - Safety of double-stapled anastomosis in low anterior resection. AB - Clinical leakage of the anastomosis follows low anterior resection for rectal carcinoma in 5-10 per cent of patients despite standard stapling techniques. A modification of this method has obviated the need for a distal purse string. A flexible transverse stapling instrument (Roticulator 55) is applied across the rectum below the tumour, and a double-staggered row of staples is inserted as a substitute for the distal purse string. End-to-end stapled anastomosis is then performed with peranal insertion of a Premium CEEA stapling instrument. In 111 patients the indications for operation were colorectal carcinoma (96 patients), diverticulosis (ten), megarectum (four) and ulcerative proctocolitis (one). Three patients had clinical evidence of anastomotic leakage; all survived. The incidence of radiological leakage on Gastrografin enema 10-12 days after operation was 9 per cent. The perioperative mortality rate was 2 per cent; all deaths were from cardiovascular causes. Local recurrence of tumour occurred in eight patients (7 per cent) after a mean follow-up of 40 months. In conclusion, double-stapled end-to-end anastomosis has made low anterior resection for rectal carcinoma a safe procedure with a low mortality rate, an acceptable local recurrence rate and minimal (clinical) anastomotic leakage. PMID- 8369942 TI - Reappraisal of radical local excision for carcinoma of the rectum. AB - Outcome in all 167 patients treated by radical local excision for rectal carcinoma between 1948 and 1984 at St Mark's Hospital was assessed in terms of the original tumour differentiation except for 15 patients with incomplete follow up or ungraded tumours. Fifty-six of the 152 patients had low-grade tumours, with one death from carcinoma in this group. Of 81 patients with average-grade tumours, ten died from carcinoma of the rectum: two after early reoperation and eight following recurrence. Six of 15 patients with high-grade tumours underwent early reoperation and three of these died from carcinoma. Among the nine patients who did not undergo early reoperation there were three related deaths (two from carcinoma, one after rectal excision for recurrence). Local excision remains a valid therapy for suitable patients with low-grade tumours but is not recommended for those with average-grade lesions. The necessity for early reoperation in patients with high-grade tumours is questioned. PMID- 8369943 TI - Multicentre study of a continent colostomy plug. AB - A multicentre clinical study was carried out to assess the performance of a new disposable device, the Conseal 1-Piece, for colostomy control and continence. Forty-three patients were studied; none had any complication at the stoma. The time elapsed since surgery and the condition of the stoma and surrounding skin were recorded. The new product was compared with the patients' usual colostomy bag, studying the following parameters: ease of application, reliability, leakage, confidence, ease of removal, adhesion and comfort. Thirty-seven patients completed the study. No complications arose, and complete faecal continence was obtained with 71.1 per cent of applications. The plug was kept in position for a mean of 11.5 h and a normal stoma bag was used for the remainder of the day. Of the 37 patients who completed the trial, 26 preferred the Conseal 1-Piece to a colostomy bag. In this preliminary study the device was easy to apply, involved no major complications and provided a high degree of continence. This product deserves further study because of its simplicity of use. However, research to improve the level of continence should continue. PMID- 8369944 TI - Anorectal function after preoperative intraluminal brachytherapy and colonic J pouch-anal anastomosis for rectal carcinoma. AB - The effects of preoperative intraluminal brachytherapy on bowel function after anoabdominal rectal resection and colonic J pouch-anal anastomosis were studied. The patients included eight not receiving irradiation (group 1), eight who received 30 Gy (group 2) and eight who received 80 Gy (group 3). Stool frequency and the incidence of soiling were significantly greater in group 3 than in the other groups. Anal resting pressure was lower in group 3 during the study period but J pouch distensibility was not reduced. The maximum tolerated volume, threshold volume and squeeze pressure were significantly lower in group 3 than in the other groups in the early postoperative period. These results suggest that high-dose brachytherapy affects the anal sphincters and colonic J pouch. A moderate dose of 30 Gy may be more suitable before restorative anorectal surgery. PMID- 8369945 TI - Pouch-vaginal fistula. AB - Between January 1976 and June 1991, 161 women underwent restorative proctocolectomy. Seventeen (10.6 per cent) developed pouch-vaginal fistula. There was no difference in the incidence of inflammatory (15 of 141; 10.6 per cent) and non-inflammatory (two of 20; 10 per cent) disease, the severity of colitis or the number of stages in the operation. In 15 patients the fistula involved the ileoanal anastomosis; in two it had possibly occurred at the dentate line. There was no significant difference in the proportion of hand-sewn (ten of 120; 8.3 per cent) and stapled (seven of 41; 17 per cent) ileoanal anastomosis. Of the 17 women, six had pelvic sepsis in the immediate postoperative period and five had an anastomotic complication. There was no case of Crohn's disease. Three patients developed a pouch-vaginal fistula before closure of the ileostomy. The remaining 14 fistulas occurred a median of 7 (range 1-144) months after closure. Five further patients were referred from elsewhere to give a total of 22 for analysis of treatment and outcome. The fistula developed before ileostomy closure in five patients (group 1) and after closure in 17 (group 2). Following treatment, six fistulas had healed with five patients still undergoing treatment. In group 1, three of the five fistulas healed, whereas in group 2 only three of the 17 healed. Eight patients required excision of the pouch. The prognosis appears to be worse when pouch-vaginal fistula occurs after ileostomy closure. The optimal management is not yet established. PMID- 8369946 TI - The future of vascular surgery. PMID- 8369947 TI - Choice of agent for peripheral thrombolysis. PMID- 8369948 TI - Selective cholangiography in laparoscopic cholecystectomy. PMID- 8369949 TI - Adjuvant herbal treatment for gallstones. PMID- 8369950 TI - Easy technique for cholangiography during laparoscopic cholecystectomy. PMID- 8369951 TI - Autotransplantation of splenic tissue in an isolated segment of small intestine. PMID- 8369952 TI - Benign parotid cysts associated with human immunodeficiency virus infection. PMID- 8369953 TI - Ankle fracture is associated with prolonged venous dysfunction. PMID- 8369954 TI - Steroid priming promotes oxytocin-induced norepinephrine release in the ventromedial hypothalamus of female rats. AB - In vivo microdialysis was used to detect norepinephrine (NE) release in the ventromedial hypothalamus of estradiol (E2)- or E2 plus progesterone (P)-treated female rats injected with 1.0 IU of oxytocin (OXY). Dialysates were collected before and after OXY administration on 3 consecutive days and analyzed for NE content by high performance liquid chromatography with electrochemical detection. After the last sample was collected on day 1, animals were injected with 3 micrograms E2 benzoate or oil. On day 3, E2-primed animals received 200 micrograms of P and control females received oil prior to OXY administration. OXY administration did not induce NE release on day 1. When OXY was administered to animals that received E2 approximately 20 h earlier, increased release of NE was not consistently seen. In contrast, E2-primed animals that received P on day 3 displayed significant increases in the release of NE after OXY administration compared to their own basal levels and to NE levels in control animals. To distinguish whether E2 priming is sufficient to promote OXY-induced release of NE without the addition of P, NE content of VMH dialysates in a second group of animals was examined following exposure to vehicle or E2 alone. When OXY was administered 24 or 48 h after estrogen priming, only 1 of 4 E2-primed females had modestly elevated dialysate NE levels. To evaluate the interactions between OXY and NE in the regulation of reproductive behavior, lordosis responses were observed in hormone-primed female rats receiving systemic injections of OXY, the alpha 1-adrenoceptor antagonist prazosin, or both OXY and prazosin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369955 TI - Chronic corticosterone administration enhances behavioral sensitization to amphetamine in mice. AB - The role of corticosterone (CCS) in regulating sensitization to amphetamine's locomotor activating effects was measured in female DBA/2 mice that had been sham operated or adrenalectomized and implanted with CCS-containing or cholesterol pellets. Three days following surgery, the mice were injected with saline and circular open field locomotor activity was measured for a 5-min time period starting 15 min after injection. Over the next 4 days, amphetamine (1.0-10.0 mg/kg) was injected and locomotor response measured. Control animals (sham operated, cholesterol pellet) showed increased locomotor activity following their first injection of 5.0 mg/kg and 10.0 mg/kg amphetamine, while ADX animals showed increased activity only after treatment with the 10 mg/kg dose. Chronic CCS treatment did not significantly alter initial responsiveness to amphetamine in either sham-operated or ADX animals, but it did alter the dose-dependent sensitization to amphetamine. Both sham-operated and ADX animals implanted with cholesterol pellets showed increased locomotor response to amphetamine (sensitization) following injection with 2.5, 5.0 and 10.0 mg/kg doses of amphetamine. However, the enhancement of locomotor activity was greater in the sham-operated control animals. CCS-treated sham-operated animals exhibited sensitization to the locomotor-activating effects of amphetamine at the lowest dose used (1.0 mg/kg) and increased stereotype following treatment with the higher doses. ADX/CCS animals developed sensitization to the locomotor-activating effects of amphetamine following chronic injection with the 2.5 mg/kg dose, and showed sensitization to amphetamine-induced stereotypy at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369956 TI - Acute anoxia-induced alterations in MAP2 immunoreactivity and neuronal morphology in rat hippocampus. AB - Cerebral ischemia induces major neuronal morphological alterations. It is not clear, however, whether this is directly caused by O2 deprivation. To determine the effect of hypoxia on cytoskeletal structures and neuronal morphology, we performed experiments and examined anoxia-induced changes in microtubule associated protein 2 (MAP2) and cell morphology in hippocampal slices in vitro. Anoxia (measured PO2 = 0 Torr) induced a marked loss in dendritic MAP2 immunoreactivity and cell swelling of hippocampal neurons by 2 h after O2 reinstitution. These changes were severe in CA1 and CA3 neurons and comparatively mild in dentate gyrus neurons. Quantitative analysis showed that 10 min of anoxia induced a 30% loss of MAP2-positive dendrites but this increased to 70% after 30 min of anoxia. A concurrent major increase in somata area of about 100% and 200% was observed in CA1 and CA3 neurons respectively. Somata area in the lower dentate gyrus, however, increased either insignificantly or by only 30% for the respective periods of anoxia. These results suggest that deprivation of O2 can by itself induce a major loss in dendritic MAP2 immunoreactivity and changes in cell morphology in hippocampal neurons. These alterations occur rapidly after hypoxia, and the severity of these changes is directly related to the duration of anoxia and brain region in the hippocampus. PMID- 8369957 TI - A comparative study of age-related changes in inhibitory processes and long-term potentiation in the lateral septum of mice. AB - Anaesthetized C57 BL/6 mice of different ages (young: 5 months; middle-aged: 15 months; and old: 21 months) were used to determine whether aging alters the efficiency of synaptic inhibition and long-term potentiation (LTP) in the lateral septum (LS). Electrical stimulation of the fimbria induced field potentials in the ipsilateral LS comprising two initial negative components (N2 and N3) followed by a positive wave of low amplitude. Paired-pulse experiments showed a facilitation of the N2 component and a concomitant depression of the N3 components. Facilitation of the N2 component was stronger in both middle-aged and old mice as compared to young mice, whereas an inverse pattern of changes was observed for inhibition of the N3 component. High-frequency stimulation of the fimbria produced a persistent increase in the N3 amplitude. This LTP was of significantly higher amplitude in both young and middle-aged mice as compared to old mice. These results suggest that aging impairs both inhibitory processes and synaptic plasticity in the mouse LS, but that inhibitory processes appear to be affected earlier. PMID- 8369958 TI - Distribution of ryanodine receptors in the chicken central nervous system. AB - The ryanodine receptor (RR), an intracellular calcium release channel, has been identified in the nervous system but its contributions to neuronal function are unknown. We have utilized immunohistochemical techniques to establish the distribution of RRs in the central nervous system (CNS) of the chick as a step toward elucidating the function of RRs in this system. RR immunoreactivity is observed throughout the brain, most prominently in large neurons. The strongest immunoreactivity is found in cerebellar Purkinje neurons, but nuclei in the motor, visual and vestibular systems are also intensely labeled, and immunoreactive neurons are observed the olfactory bulb and the hippocampus. In these neurons, labeling is prominent in cell bodies, dendrites and axons, but is not observed in the dendritic spines or in plasma membranes. The neuronal RRs bind [3H]ryanodine with high affinity and this activity is regulated by calcium, caffeine, MgCl2/ATP and ionic strength. Multiple forms of the RRs are found in the chicken CNS. Immunoprecipitation and localization studies using RR isoform specific monoclonal antibodies reveal major differences in their distribution. The predominant species in the cerebellum is similar to the skeletal muscle isoform while there is a lower level of expression of either the cardiac or beta skeletal isoforms. In the remainder of the brain, the predominant isoform is similar to the cardiac or beta skeletal muscle isoforms. The broad distribution of RRs in the CNS suggests that calcium release events mediated by these proteins may have a functional role in a diverse array of neurons. Moreover within the populations of neurons expressing RR's, the presence of specific RR isoforms may correlate with specialization in the calcium release events mediated by these proteins. PMID- 8369959 TI - Suprachiasmatic circadian pacemaker of rat shows two windows of sensitivity to neuropeptide Y in vitro. AB - The geniculohypothalamic tract carries visual information from the intergeniculate leaflet to the suprachiasmatic circadian pacemaker. NPY, found in this projection, has been shown to affect the phase of behavioral rhythms and influence photic entrainment. We now demonstrate that NPY, when briefly applied to the geniculate projection sites of rat SCN in vitro, induces permanent phase shifts in the rhythm of neuronal electrical activity at two separate phases of the circadian cycle. PMID- 8369960 TI - GABA decreases in the spinal cord dorsal horn after peripheral neurectomy. AB - A significant fall in the number of GABA-immunoreactive cells in laminae I-III of the rat spinal cord occurred in the somatotopic area of projection of the sciatic nerve after nerve transection. The decrease started at 2 weeks post-neurectomy, and at 4 weeks ipsilateral mean cell numbers were approximately 72% of contralateral control values. Similarly, the concentration of GABA in spinal homogenates was significantly reduced 4 weeks post-neurectomy. These data, together with our recent finding of an increase in spinal GABA during chronic inflammation of the hindlimb, suggest that the level of GABA in the dorsal horn is regulated by the amount of primary afferent input. PMID- 8369961 TI - Nerve growth factor does not influence the expression of beta amyloid precursor protein mRNA in rat brain: in vivo and in vitro studies. AB - We investigated the effect of NGF on amyloid precursor protein (APP) mRNA levels in the rat septal/nucleus basalis system. Total APP mRNA and APP 695 mRNA were determined in basal forebrain primary cell cultures exposed acutely and chronically to NGF (150-300 ng/ml) and, in vivo, in the septal area and striatum of rat pups after multiple intracerebroventricular injections of NGF. The trophic factor was able to affect cholinergic neurons in both paradigms, as evidenced by the significant increase of choline acetyltransferase (ChAT) activity induced by NGF in cell cultures (+80%) and in the striatum (+240%) of rat pups. In spite of this effect, no significant change of APP mRNA expression was observed in neuronal cultures and brain tissues. These data indicate that the neurotrophic effect of NGF on forebrain cholinergic neurons is not always associated with an alteration of APP expression. PMID- 8369962 TI - Melatonin release from pineal cells of diurnal and nocturnal birds. AB - Melatonin release from the pineal cells of chicks, pigeons and crows (diurnal birds) in vitro was compared with that from owls (a nocturnal bird). The pineal cells of diurnal birds secreted large amounts of melatonin during the dark period, whereas owl pineal cells released virtually no melatonin over 24 h and did not respond to exogenous stimulant agents. Histological examination revealed that the owl pineal gland is very small and has a poor vascular network. These results suggest that the pineal gland of owls may have degenerated and is not involved in the circadian clock mechanism in this species. PMID- 8369963 TI - Effect of transient forebrain ischemia on superoxide dismutases in gerbil hippocampus. AB - Substantial generation of oxygen-derived free radicals has been implicated in pathophysiology of ischemic brain damage. Immunoreactive mitochondrial manganese and cytosolic copper-zinc superoxide dismutases, initial and essential enzymes to scavenge superoxide radical anions, increased in the gerbil hippocampal neurons after transient forebrain ischemia. Neuronal cells responded to oxidative stress in ischemia and induced the protective mechanism to increase superoxide dismutases. PMID- 8369964 TI - The wind-elicited escape response of cockroaches (Periplaneta americana) is influenced by lesions rostral to the escape circuit. AB - When the escape response of the cockroach (Periplaneta americana) is triggered by wind, it is mediated by the cercal-to-giant interneuron pathway and leg motor circuitry, within the abdominal and thoracic portions of the ventral nerve cord. We have found that a lesion rostral to the thorax (transection of a cervical connective) produces specific changes in wind-evoked escape. Lesioned animals reliably displayed short-latency responses to wind. However, the orientation of the initial turning component of escape was altered and the duration of subsequent running was reduced. Preliminary physiological study suggests that changes in the orientation of escape reflect changes in the integration of wind sensory signals by thoracic circuitry. These findings imply that rostral centers influence sensorimotor integration underlying wind-evoked escape. PMID- 8369965 TI - Acute effects of reserpine on tryptophan hydroxylase activity and mRNA in rat brain. AB - The present study examined changes in tryptophan hydroxylase (TPH) activity in the rat brainstem 1-4 days after i.p. reserpine administration. TPH enzyme activity was significantly decreased day 1 posttreatment and followed by a small but significant increase on days 2-4. Maximal TPH activity on day 4 was elevated only 42% above control level. This small increase in TPH activity was not preceded by any change of in situ hybridization signal of TPH message on day 1. In contrast, adrenal tyrosine hydroxylase (TH) activity in these same reserpinized animals was 2.5-fold higher than control on 4 day posttreatment. In addition, TH message was correspondingly increased day 1 posttreatment. Taken together, these results indicate a trend of small increase in TPH activity and no alteration in message after reserpine treatment unlike catecholaminergic systems. PMID- 8369966 TI - Characterization of neurons born and incorporated into a vocal control nucleus during avian song learning. AB - In male zebra finches, song learning is accompanied by the addition of new neurons to Area X, a nucleus necessary for normal song development. We examined whether Area X neurons born after 15 days post-hatch are recruited into the efferent pathway from Area X to the dorsolateral nucleus of the medial anterior thalamus (DLM). Our data suggest that the majority of these new Area X neurons are interneurons and that DLM-projecting neurons are incorporated into Area X prior to song learning. PMID- 8369967 TI - Morphine-induced potentiation of brain stimulation reward is enhanced by MK-801. AB - Morphine (2.5 mg/kg, i.p.) and MK-801 (0.05 mg/kg, i.p.) each enhanced the rewarding impact of electrical stimulation of the medial forebrain bundle, causing small but reliable parallel leftward shifts of the functions relating response rate to stimulation frequency. Administration of MK-801 and morphine together caused a profound leftward shift in the functions. This effect was not due to sensitization to either drug, and suggests that disruption of glutamatergic function can potentiate the rewarding impact of opiates. PMID- 8369968 TI - Reciprocal synaptic relations between CRF-immunoreactive- and TRH-immunoreactive neurons in the paraventricular nucleus of the rat hypothalamus. AB - By double immunoelectron microscopy, we studied synaptic relations between corticotropin-releasing factor (CRF)-immunoreactive (ir) and thyrotropin releasing hormone (TRH)-ir neurons in the paraventricular nucleus (PVN) of the rat hypothalamus. CRF-ir and TRH-ir neurons made reciprocal synaptic connections in the medial and periventricular parvocellular regions. These results may suggest that both the parvocellular neurons interplay on their hypophysiotropic functions within the PVN. PMID- 8369969 TI - Hypothalamic but not cortical grafts induce recovery of sexual behavior and connectivity in medial preoptic area-lesioned rats. AB - We have previously shown that hypothalamic fetal brain grafts induced recovery of sexual behavior in medial preoptic area (MPOA)-lesioned male rats. In the present series of experiments, male rats with completely abolished sexual behavior by MPOA lesions received either hypothalamic or frontal cortical fetal grafts. The animals that received hypothalamic grafts showed a gradual recovery of sexual behavior. In contrast, those animals who received cortical grafts did not recover sexual behavior during the 15 weeks after the graft. In addition, to evaluate the connectivity of the grafted tissue with the host brain, a retrograde tracer, fluorogold, was injected in the dorsal tegmental area. Fluorogold-labeled cells were found in the hypothalamic, but not in the cortical grafts. These results suggest that specificity of the grafted tissue and connectivity between brain grafts and host tissue are necessary for the recovery of male sexual behavior in MPOA-lesioned rats. PMID- 8369970 TI - Thymopoietin, a thymic polypeptide, prevents nicotinic agonist-induced morphological changes in neonatal muscle cells in culture. PMID- 8369971 TI - Dissecting cockroach allergens. PMID- 8369972 TI - Pre- and post-natal events leading to allergen sensitization. PMID- 8369973 TI - The role of CD8+ T cells in the regulation of IgE. PMID- 8369974 TI - Food allergy in childhood. Hypersensitivity to cows' milk allergens. PMID- 8369975 TI - Evidence for an increase in atopic disease and possible causes. PMID- 8369976 TI - Isolation and in vitro translation of messenger RNA from the American cockroach. AB - Total RNA was extracted from the whole body of American cockroach (Periplaneta americana) using chaotropic salt guanidine isothiocyanate in the presence of 2 mercaptoethanol (2-ME). Polyadenylated mRNA was isolated by oligothymidylic acid cellulose chromatography and mRNA was translated using a rabbit reticulocyte lysate system. The translation, as judged by the incorporation of 35S-methionine, was obtained with poly(A)+ RNA, where an approximately 9.5-fold increase in label incorporation over control was achieved. Analysis of translation products by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) in combination with autoradiography showed that many proteins with apparent molecular weights ranging from 12 to 200 kD were synthesized, and no labelled proteins were found with negative RNA control and poly(A)- RNA. Immunoprecipitation studies performed using polyclonal and monoclonal antibodies revealed that synthesized proteins of MW 90, 78, 72, 49, 45, and 26 kD corresponded with previously identified principal and major allergens of American cockroach from our laboratory. In addition, the allergenicity of the translation mixtures was also confirmed by fluoroallergosorbent test (FAST) inhibition studies with IgE antibodies of human reaginic serum pool. PMID- 8369977 TI - Seasonal enhancement of IL-4 induced IgE synthesis by peripheral blood mononuclear cells of atopic patients. AB - The role of IL-4 on IgE synthesis has been well established. IL-4 has been shown to promote IgE production by B cells from atopic and non-atopic donors. In this study, the effects of natural exposure to pollens on IL-4-induced IgE synthesis by peripheral blood mononuclear cells of atopic and non-atopic donors were examined. The results confirm production of IgE in an IL-4 dose-dependent manner by PBMC cultures of these two groups. When cultures were performed out of the pollen season, following stimulation by IL-4, no significant differences was observed between the levels of IgE produced by PBMC of atopic and non-atopic donors. In contrast, upon natural exposure to pollens, significant higher levels of IgE were measured in the atopic group than in the non-atopic one. These results show that the pollen season influences the IL-4-induced IgE synthesis by PBMC of allergic patients and are in keeping with seasonal rise of specific IgE antibodies. PMID- 8369978 TI - The effect of genetic and environmental factors on the prevalence of allergic disorders at the age of two years. AB - The effect of genetic and environmental factors on the prevalence of allergic disorders in early childhood was determined in a prospective follow-up study. Information was available on 1174 children at the age of 2 years. Two-hundred and seventy-five were considered to have an allergic disorder. The prevalence varied from 3.2% for rhinitis to 10.9% for asthma. At 2 years 60 children reacted positively on skin-prick test (SPT). Multivariate logistic regression analysis was used to obtain adjusted odds ratios (95% confidence interval) for each factor. For asthma, positive family history, male sex, low birth-weight, maternal smoking and season of birth were significant risk factors. For eczema, positive family history was the only significant risk factor. For rhinitis, lower socio economic group and autumn birth were significant. Male sex and low birth-weight were significant for skin test positivity. Positive family history and low birth weight were significant risk factors for any allergy. Low birth-weight was also a significant risk for skin test reactivity to house dust mite. Genetic and environmental factors have a profound effect on the development of allergic disorders in the first two years of life. PMID- 8369979 TI - The effect of zardaverine, an inhibitor of phosphodiesterase isoenzymes III and IV, on endotoxin-induced airway changes in rats. AB - Zardaverine is a novel phosphodiesterase III/IV inhibitor, developed as a potential therapeutic agent for asthma. In this study we evaluated the effect of zardaverine in an in vivo animal model of airway inflammation and hyperresponsiveness. Endotoxin exposure in rats causes a transient increase in airway responsiveness and a neutrophilic inflammation of the bronchi, which are both at least partly mediated through the secondary release of tumour necrosis factor alpha (TNF alpha). Groups of 10 animals each were pretreated with placebo or zardaverine (1, 10, 30 mumol/kg) i.p., 30 min prior to exposure to aerosolized endotoxin (LPS) or saline. Ninety minutes later, airway responsiveness to 5-HT was assessed and bronchoalveolar lavage (BAL) performed. Zardaverine did not influence baseline lung resistance (RL), but inhibited dose dependently the 5-HT induced increase in RL in control animals. In placebo pretreated animals LPS exposure caused a significant decrease in PC50RL5-HT (provocative concentration of 5-HT causing a 50% increase in RL), compared to the saline exposed control group (1.1 +/- 0.1 vs 2.7 +/- 0.4 micrograms/kg) (P < 0.01). This decrease in PC50RL5-HT was significantly inhibited by zardaverine 30 mumol/kg (5.4 +/- 1.8 vs 1.1 +/- 0.1 micrograms/kg) (P < 0.05). Compared to placebo pre-treated, LPS exposed animals, zardaverine 30 mumol/kg also significantly inhibited to LPS induced neutrophil increase (193.0 +/- 50.0 vs 915.6 +/- 181.3 x 10(3)) (P < 0.01), increase in elastase activity (23 +/- 11 vs 54 +/- 9 nmol substrate/h/ml) (P < 0.05) and TNF alpha release in BAL fluid (93.1 +/- 19.5 vs 229.5 +/- 24.8 U/ml BAL fluid) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8369980 TI - Effect of oral and inhaled cetirizine in allergen induced bronchoconstriction. AB - Cetirizine is a potent, selective H1 histamine receptor antagonist. The effect of oral and inhaled cetirizine was assessed on the early bronchoconstrictor response to inhaled allergen in 10 mild atopic asthmatic patients in a double-blind, randomized, placebo controlled trial. All were sensitive to Dermatophagoides pteronyssinus and this was used as the provoking allergen. The geometric mean PD20 FEV1 values obtained at allergen challenge were measured as cumulative breath units (c.b.u.) and following oral cetirizine, inhaled cetirizine and placebo were 124.5, 75.7 and 76.7 c.b.u. respectively. These did not differ significantly. We conclude that neither oral nor inhaled cetirizine significantly attenuates the early response to inhaled allergen in atopic asthmatic subjects. However, the method of repeated allergen challenge is likely to be relatively insensitive. PMID- 8369981 TI - House dust mite exposure as a cause of asthma. PMID- 8369982 TI - Risks of infantile atopic dermatitis from parental atopy. PMID- 8369983 TI - Paracetamol anaphylaxis. PMID- 8369984 TI - Extracellular and intracellular action of clodronate in osteolytic bone diseases? A hypothesis. PMID- 8369985 TI - The effects of walking at the anaerobic threshold level on vertebral bone loss in postmenopausal women. AB - The purpose of this study was to determine the optimal intensity of exercise necessary to prevent the postmenopausal bone loss on the basis of anaerobic threshold (AT). Thirty-three postmenopausal women were randomized to control (group C: n = 12) or two exercise groups (group H and group M). All women performed a treadmill exercise test, and the AT was measured by expired gas analysis. The exercise regimen consisted mainly of walking at a speed that kept the exercise heart rate above the AT (group H: n = 12) or below the AT (group M: n = 9). Exercise was performed for 30 minutes, three times a week for 7 months. The bone mineral density (BMD) of the lumbar vertebrae was measured using dual energy X-ray absorptiometry. The BMD level in group C decreased by 1.7 +/- 2.7%, but there was a significant increase of 1.1 +/- 2.9% in group H. In group M there was a decrease of 1.0 +/- 3.1% which did not differ from group C. In group C, serum osteocalcin and urinary hydroxyproline excretion were significantly increased, but no changes were seen in either of the exercise groups. Urinary calcium significantly decreased in the exercise groups. We conclude that short term (7 months) exercise with intensity above the AT is safe and effective in preventing postmenopausal bone loss. PMID- 8369986 TI - Neutrophil functions in patients with fractures of the upper end of the femur. AB - In the present study, neutrophil functions were examined in vitro in 40 patients suffering from fractures of the upper end of the femur (trochanteric and subcapital). Adherence to nylon, serum chemotaxis, and phagocytosis-bactericidal function were assayed. Three microbial strains, namely, Staphylococcus aureus, S. epidermidis, and Pseudomonas aeruginosa, were used for the experiments. Adherence of the patients' neutrophils was found normal. On the contrary, the chemotactic ability of the patients' sera was inferior to that of healthy controls; phagocytosis and bactericidal function were also significantly impaired for all three bacterial strains. The results were independent of fracture site (intracapsular or extracapsular), sex, and age. The observed host defense disorders provide additional information that helps to explain the increased susceptibility of these patients to bacterial infections. PMID- 8369987 TI - Serum bone Gla protein as a marker of bone turnover in acromegaly. AB - Serum bone Gla protein, a sensitive and specific marker of bone turnover, was measured in 35 acromegalic patients (14 untreated, 8 clinically active, and 13 cured) and 21 controls. We also examined 10 acromegalic patients before and after transsphenoidal surgery. Untreated and clinically active acromegalic patients had significantly higher serum bone Gla protein concentrations than the control subjects. Other nonspecific biochemical markers of bone metabolism, such as urinary hydroxyproline and urinary calcium, were also present in significantly greater amounts in active acromegalic patients. After treatment, a significant decrease in levels was observed, with return to control levels. In acromegalic patients, positive correlations were found among serum bone Gla protein and serum growth hormone and serum insulin-like growth factor I levels, as well as among levels of insulin-like growth factor I and serum phosphorus, serum alkaline phosphatase, and urinary hydroxyproline. These results suggest that serum bone Gla protein is a sensitive marker of the action of growth hormone in bone metabolism in acromegaly, a role that is probably mediated by insulin-like growth factor I. PMID- 8369988 TI - Bone mineral density in hyperandrogenic amenorrhoea. AB - The authors assessed bone mineral density in androgenized amenorrheic (group A; n = 9) and androgenized nonamenorrheic patients (group B; n = 30) and compared it with controls (n = 22). Bone mineral density of group A patients (1.023 +/- 0.045 g/cm2) did not differ from controls (1.047 +/- 0.83 g/cm2); both groups had significantly lower values than group B women (1.099 +/- 0.085 g/cm2). Of the hormonal variables explaining bone mineral density in androgenized women, only dehydroepiandrosterone sulfate had a significant negative correlation (r = 0.45). In contrast to other forms of amenorrhea, women with hyperandrogenic amenorrhea seem to be spared from osteopenia. PMID- 8369989 TI - Life-style and different fracture prevalence: a cross-sectional comparative population-based study. AB - In order to explain the higher prevalence of fractures in urban compared with rural areas, 782 residents in the city of Malmo, Sweden and 486 inhabitants from the nearby rural municipality of Sjobo were invited to participate in a sex- and age-matched cross-sectional study on life-style differences; 73 and 80% respectively responded. Responders answered a questionnaire on medical and social background and were interviewed on past and present physical activity. The men and women of the rural area were found to be significantly more active physically at work and during spare time. Housing was larger in the rural area. For women, these differences are decreasing in the younger age groups. Bone mass was found to be correlated to heavier work load for men. Other life-style variable such as dairy calcium intake, coffee drinking, estrogen medication, and morbidity, could not explain this difference. Higher prevalence of fractures in the city could therefore be explained by physically less active life-style. PMID- 8369990 TI - Misoprostol, a prostaglandin E1 analogue, inhibits basic calcium phosphate crystal-induced mitogenesis and collagenase accumulation in human fibroblasts. AB - Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathy. BCP crystals induce the secretion of matrix-degrading enzymes such as collagenase. No prophylactic or therapeutic agents are recognized to ameliorate the cartilage damage associated with BCP deposits in joints. As a chondroprotective effect of prostaglandins (PG) has been suggested, we studied the effect of misoprostol, a PGE1 analogue, on BCP crystal-induced mitogenesis and collagenase messenger RNA (mRNA) accumulation in human fibroblasts (HF). Mitogenesis was determined by 3H-thymidine incorporation assays and collagenase mRNA accumulation by Northern blot analysis, in HF stimulated with BCP crystals in the presence or absence of misoprostol. Misoprostol caused concentration dependent inhibition of BCP crystal-induced mitogenesis. The inhibition of BCP stimulated mitogenesis was not specific as misoprostol also inhibited the mitogenic response to 10% serum. There was only 50 (+/-5)% inhibition of serum induced mitogenesis by misoprostol at 500 ng/ml, the concentration that completely inhibited BCP crystal-induced mitogenesis. Misoprostol also inhibited the accumulation of collagenase mRNA in BCP-stimulated HF by 63%. These data suggest that misoprostol may inhibit the synovial proliferation and cartilage degradation that accompany BCP crystal deposition. PMID- 8369991 TI - Evidence that interleukin-1 mediates its effects on bone resorption via the 80 kilodalton interleukin-1 receptor. AB - Interleukin-1 (IL-1) mediates its effects through two distinct receptors, one of 80 kilodaltons (80 kD) present in athymic lymphocytes and fibroblasts, and one of 60 kD present in cells of the monocyte-macrophage lineage. A novel monocyte cytokine in the IL-1 family which binds to both the 80 and the 60 kD receptors has been purified, cloned, and expressed. As the interleukin-1 receptor antagonist (IL-1ra) has been shown to inhibit bone resorption in organ culture, it is not clear whether these effects are mediated through the 80 or the 60 kD receptor. Recently, neutralizing antibodies (35F5) have been developed to the 80 kD receptor which inhibit IL-1 effects mediated through this receptor. To determine the importance of the 80 kD receptor to IL-1-mediated bone resorption, we used the neutralizing antibodies (35F5) to the 80 kD receptor to determine if they inhibited bone resorption stimulated by IL-1 in bone organ cultures. The 35F5 antibody blocked bone-resorbing activity due to IL-1 completely, and also blocked control or "endogenous" bone-resorbing activity present in murine bone organ cultures incubated in control media. The 35F5 antibody had no effect on bone resorption mediated by tumor necrosis factor (TNF), or parathyroid hormone (PTH). These data suggest that the availability of the 80 kD IL-1 receptor is required for osteoclastic bone resorption mediated by IL-1. PMID- 8369992 TI - Effect of prostaglandin D2 on the femoral bone mineral density in ovariectomized rats. AB - We studied the effects of prostaglandin D2 (PGD2) on the femoral bone mineral density (BMD) and other related parameters in ovariectomized (OVx) and sham operated rats. BMD was measured in vivo by dual energy X-ray absorptiometry (DXA) for the period of 36 days or 112 days after operation. When 9- or 10-week-old rats were used at the time of operation, the femoral BMD increased during these periods. Ovariectomy resulted in a marked suppression of this steady increase in BMD at both proximal and distal ends of the femur. Subcutaneous administration of a slow-release preparation of PGD2 on days 1 and 21 not only prevented the ovariectomy-induced suppression of BMD, but also augmented the steady increase in BMD of the sham-operated rats. When medication was started on day 70, the depressed rate of increase in BMD was restored to the control level. Serum calcitonin (CT) and parathyroid hormone (PTH) levels were not affected by either ovariectomy or by PGD2 administration. Body weight and bone length were increased, but uterine weight was decreased by ovariectomy. PGD2 administration showed no effects on these parameters. There was a significant increase in the fasting level of urinary hydroxyproline excretion after ovariectomy, and PGD2 administration had no significant effect on this parameter either. These results indicate that the prevention of osteopenia in OVx rats and the increase in BMD in sham-operated and post-OVx rats by PGD2 administration are due to its stimulatory effect on bone formation. PMID- 8369993 TI - Histomorphometry of iliac crest trabecular bone in adult male baboons in captivity. AB - Data in the literature on bone histomorphometry in the baboon are scant. This study provides data from analysis of trabecular bone of the iliac crest of 16 adult male chacma baboons (Papio ursinus) in captivity. Five animals were young adults judging by the presence of growth cartilage in the iliac crest biopsy. Bone volume resembled that in humans, but trabeculae were thinner and more closely spaced. Bone turnover appeared somewhat lower than in humans. Coupling of resorption and formation was excellent as judged by cellular and kinetic variables; erosion surface was an unreliable indicator of ongoing coupling. The similarities between human and baboon trabecular bone make the baboon suited for the study of microstructure and bone turnover of trabecular bone with relevance to humans. PMID- 8369994 TI - Purified Pasteurella multocida protein toxin reduces acid phosphatase-positive osteoclasts in the ventral nasal concha of gnotobiotic pigs. AB - To study the in vivo response of conchal (turbinate) osteoclasts to Pasteurella multocida toxin, four gnotobiotic pigs (7 days of age) were inoculated subcutaneously with 0.2 microgram/kg of purified toxin. One toxin-treated pig along with one control pig were necropsied at 2, 5, 9, and 14 days postinoculation. The entire length of nasal concha from the nasal planum toi ethmoid region was removed, blocked by transverse cuts into five areas, decalcified, sectioned, and then stained with tartrate-resistant acid phosphatase (TRAP) to identify osteoclasts. In each section, total area of concha, total osteoclast cytoplasmic area, and number of osteoclasts were determined using an image analysis morphometric unit. Also collected from pigs were blood and serum for complete blood counts, electrolyte levels, liver enzymes, and TRAP levels. Conchal atrophy increased in severity with time after 2 days postinoculation. In general, the ventral conchae from toxin-treated pigs at 9 and 14 days postinoculation had decreased surface area, osteoclast cytoplasmic area, and numbers of osteoclasts. Serum levels of TRAP were mildly elevated when compared with age-matched controls. No other significant alterations in blood cells or chemistries occurred and no lesions were present histologically in tissues (liver, kidney, lung, heart, and spleen) other than concha. This study shows that the P. multocida toxin induces rapid bone resorption and increases serum levels of acid phosphatase but leads to diminished acid phosphatase expression and presumably, numbers of osteoclasts. PMID- 8369995 TI - The effect of high or low dietary calcium on bone and calcium homeostasis in young male rats. AB - Young male rats (100 g body weight) were fed diets containing varying amounts of calcium. Body weight and bone development were studied together with various endocrine parameters, including blood levels of Ca2+, calcitonin, parathyroid hormone, vitamin D, and gastrin, and the enterochromaffin-like (ECL) cell-related parameters gastric mucosal histidine decarboxylase activity and histamine concentration. A diet containing 0.5% calcium resulted in optimum body weight gain and bone development. A lower calcium intake impaired body weight gain and bone development. The impairment was manifested in reduced bone calcium content whereas the size of the bones was unaffected. The net absorption of calcium seemed to be proportional to the calcium intake. A low calcium diet (0.03%) raised the circulating levels of 1,25(OH)2D and parathyroid hormone and lowered 25(OH)D3 and Ca2+, whereas a high calcium diet (5.46%) raised calcitonin, Ca2+, 25(OH)D3, and 1,25(OH)2D. In addition, the low calcium diet lowered the circulating gastrin concentration and the histidine decarboxylase activity and histamine content of the ECL cells in the gastric mucosa. A high calcium diet raised the circulating gastrin concentration, but the rise was not associated with an increase in the histidine decarboxylase activity and histamine content. PMID- 8369996 TI - Type II collagen expression in the mandibular condyle during growth adaptation: an experimental study in the rabbit. AB - An experiment was designed to mimic orthopedic functional appliances in order to investigate the spatial and temporal characteristics of type II collagen secretion as a marker of cartilage maturation in the mandibular condyle of young rabbits. The position of the glenoid fossa in relation to the condyle was altered so that articulation now took place more posteriorly. Histological sections of the condyles of 15-, 20- and 30-day-old experimental and control animals were stained with toluidine blue and with an anti-type II collagen antibody. A widened progenitor cell layer was found posteriorly in the experimental condyles and a narrow layer was found anteriorly to the articulating region. The chondroblast layer was also widened posteriorly, whereas the hypertrophic cell zone was narrower; the opposite was seen anteriorly. The effect was marked in 15- and 20 day-old animals and weak in 30-day-old animals. Type II collagen stain and strong toluidine blue metachromasia were not observed in the progenitor cell zone until the chondroblasts had acquired a flattened, slightly hypertrophic morphology, which was found deeper in the experimental condyles than in the controls. This is interpreted as a slowing down of the differentiation of chondroblasts as a result of the force applied. The effect of masticatory function may also be explained in terms of delayed differentiation of chondroblasts and increased growth. PMID- 8369997 TI - Correlation between densitometric and hystomorphometric values in isolated vertebrae of Sprague-Dawley rats. AB - The study of bone mass in experimental animals usually requires invasive techniques. Dual energy X-ray absorptiometry (DEXA) may be an alternative as a non-invasive method (1). Bone mineral density (BMD) and bone mineral content (BMC) of 62 vertebrae of Sprague Dawley rats (SDr) measured by DEXA densitometry were compared with histomorphometric bone volume measurements, and a statistically significant correlation was found (r = 0.79 and 0.75, respectively, p < 0.001). In conclusion, DEXA is an accurate and feasible technique for the study of trabecular bone mass in SDr. PMID- 8369998 TI - Computer-based training: training approach of choice. PMID- 8370000 TI - Bedside terminals and quality of nursing documentation. AB - In this article, the authors report on part one of a three-part investigation studying the impact of bedside terminals at New York University Medical Center, New York, NY. Using a before-after parallel control-group design, the quality of computerized nursing documentation was studied before and after adding computers to patient rooms. The quality of documentation was defined by timeliness and completeness of data. The study hypothesis, which predicted a positive relationship between the presence of bedside terminals and the quality of nursing documentation, was not supported. Study results showed a minimal use of the computer terminals located in patient rooms. A surprising result was the use of terminals located in rooms other than that of the patient for which documentation was made. PMID- 8369999 TI - A computer assisted tutorial for applications of computer spreadsheets in nursing financial management. AB - A computer-based tutorial for teaching nursing financial management concepts was developed using the macro function of a commercially available spreadsheet program. The goals of the tutorial were to provide students with an experience with spreadsheets as a computer tool and to teach selected financial management concepts. Preliminary results show the tutorial was well received by students. Suggestions are made for overcoming the general lack of computer sophistication among students. PMID- 8370001 TI - Hybrid expert-system approach to nurse scheduling. AB - The objective of this research was to develop a hybrid expert system entitled NURSE-HELP to achieve flexible and effective scheduling for nurses. NURSE-HELP was developed with the emphasis on following the ergonomics guidelines, which will improve the performance of nurses. Moreover, the combination of linear zero one goal programming and an expert system program reduces the program run time while maintaining the quality of the schedule. The system was evaluated by comparing 18 sets of 4-week schedules generated by the head nurses manually and by NURSE-HELP. Concerning the amount of time required to generate the schedules, NURSE-HELP averaged less than 20 minutes, whereas head nurses spent from 2 to 4 hours. The quality of the schedules was measured using the following four criteria: 1) minimum staff level not satisfied, 2) day off request not granted, 3) backward rotation, and 4) maximum consecutive work periods on the night shift. NURSE-HELP was superior in all these aspects. PMID- 8370003 TI - Optimizing computer-based system use in health professions' education programs. AB - The use of computer-based systems to support training in health profession education programs has been discussed and analyzed for more than 10 years. The literature is rich with examples of how using these systems can benefit programs by more effectively distributing human resources, by making the delivery of instruction more individual and more flexible, by expanding the professional and technical competence of trainees, and by improving the monitoring of trainee performance. Obstacles to and conventional recommendations for the broadened use of computer-based systems are discussed, and an additional set of system design characteristics are described that health care educators can use in their preview and specifications for procurement of more effective computer-based systems in their training settings. PMID- 8370002 TI - Evaluation of a labor and delivery videodisc simulation. AB - The purpose of this project was to determine the impact of an interactive videodisc (IVD) simulation in labor and delivery on the learning and clinical confidence of junior-level nursing students. Two clinical groups of students were created from the total 39 and both groups were pretested on knowledge and clinical confidence. Group 1 (n = 18) completed the IVD program before the first clinical experience in the labor and delivery setting. Group 2 (n = 21) received a traditional clinical experience first and then completed the IVD program. Students completing the IVD program plus the clinical experience had significantly greater clinical confidence and learning than those students completing only the clinical experience. Evaluation comments provided suggestions for improvements and were filled with positive comments about the program. PMID- 8370004 TI - Bedside/point-of-care technology: the 'window' into the integrated clinical database, Part 4. PMID- 8370005 TI - Effect of dynamization of a static interlocking nail in promoting fracture healing. PMID- 8370006 TI - Evaluation of new surgical procedures. PMID- 8370007 TI - Stenosis of stapled colorectal anastomosis. PMID- 8370009 TI - Effect of dynamization of a static interlocking nail on fracture healing. AB - A retrospective study was done of 22 patients with complex femoral (11) and tibial (11) shaft fractures treated with static interlocking nailing followed by dynamization, which was carried out on average 7.8 months later. The success rate was 54% with no significant difference between the healing of femoral and tibial fractures. The follow-up was at least 2 years. The interval from nailing to dynamization did not correlate with the success rate; the longest interval associated with successful healing was 20 months. The authors found that static interlocking nailing without dynamization can still produce a high union rate, and if there is sparse callus formation during the healing process, indicating low osteogenesis, dynamization will result in fracture union in only half the cases. To improve the union rate, cancellous bone grafting may be necessary. PMID- 8370008 TI - Consensus conference on well-differentiated thyroid cancer: a summary. AB - OBJECTIVE: To update recommendations for the surgical treatment of well differentiated thyroid cancer. DATA SOURCES: Literature reviews and personal files. STUDY SELECTION: Panelists selected relevant articles to make arguments for and against current recommendations for the surgical treatment of well differentiated thyroid cancer. OUTCOMES: Four aspects of surgical treatment were considered: (a) the extent of surgical resection, (b) the definition and utilization of high- and low-risk patient groups, (c) who should perform thyroid surgery and (d) the use of radioactive iodine. RECOMMENDATIONS: Total thyroidectomy is not the treatment of choice for all well-differentiated thyroid cancers. The use of risk factors help select those patients in whom a total thyroidectomy would be of benefit. High-risk patients are those who are considered at high risk according to the AGES and AMES classifications or who have lymph-node metastases, aggressive variants of their disease, multifocal cancer or disease in the contralateral thyroid lobe and a history of radiation to the neck. Those at low-risk are those previously described as being at low risk according to the AGES and AMES classifications. General surgery training programs across Canada need to ensure that their residents obtain enough experience in thyroid surgery that as general surgeons they can perform this type of surgery with low morbidity. CONCLUSIONS: The findings of this consensus conference were supported by those of several review articles and by the arguments put forward by the panelists. These findings are only guidelines as to the surgical approach to well-differentiated thyroid cancer. PMID- 8370010 TI - Double stress fracture of the tibia in the presence of arthritis of the knee. AB - Two cases of double stress fracture of the tibia are described. Both patients had severe medial compartment arthritis of the knee and some varus bowing of the tibia prior to the stress fractures. The deformities were corrected by tibial osteotomies. Total knee replacement was not required. PMID- 8370011 TI - Osteomyelitis of the spine due to Salmonella: case report, review of clinical aspects, pathogenesis and treatment. AB - Osteomyelitis of the spine caused by Salmonella is rare. The authors describe a case in which the patient had fusion of the L1 and L2 vertebrae, which were affected by osteomyelitis. The infecting organism was Salmonella typhimurium. The authors describe the relationship of the vascular anatomy to the development of osteomyelitis of the spine. They discuss the clinical features, diagnosis, pathogenesis and treatment of the disease. Although the association of osteomyelitis due to Salmonella and sickle cell disease has long been known, this patient did not have sickle cell disease or any other condition that would compromise the immune system. PMID- 8370012 TI - Arm problems and psychological distress after surgery for breast cancer. AB - The frequency of problems in the arm affected by surgery for breast cancer and the association of these problems with psychological distress were assessed among 223 women with newly diagnosed breast cancer 3 months after operation and again 15 months later among 201 of these same women. At 3 months after operation, 182 (82%) of the 223 patients reported at least one arm problem. Specific problems reported were swelling (24%), weakness (26%), some limitation in range of movement (32%), stiffness (40%), pain (55%) and numbness (58%), and these percentages had changed little 15 months later. Regardless of the type of mastectomy, women who underwent axillary dissection had more arm problems. Compared with women reporting no arm problems, the adjusted odds ratios of having psychological distress at 3 months for women reporting one to two, three to four and five to six arm problems were 1.2, 2.3 and 3.1 respectively (chi 2 for trend = 9.5, p = 0.002). Arm problems are frequent after operation for breast cancer, and these problems appear to increase the likelihood of psychological distress. Women should be informed that arm problems are expected but non-threatening sequelae of initial surgical treatment for breast cancer. PMID- 8370013 TI - Laparoscopic inguinal herniorrhaphy. AB - Between September 1991 and April 1992, 30 patients were admitted for repair of an inguinal hernia. Four elderly patients were excluded because of other medical conditions. Of the remaining 26 patients laparoscopic hernia repair was carried out successfully in 24; the procedure was abandoned in 2 because of dense adhesions in the pelvis from inflammatory disease. Nineteen of the 24 patients were discharged within 24 hours of operation; the other 5 were treated as outpatients. All patients returned to their normal employment within 7 days of operation. There were no wound infections and no evidence of recurrence at follow up of up to 10 months. The authors believe that laparoscopic repair may usher in a new era of hernia management. PMID- 8370014 TI - Surgical and postoperative management of two neonates with necrotizing fasciitis. AB - Two neonates who presented with necrotizing fasciitis (NF) secondary to omphalitis were treated by radical excision of the anterior abdominal wall. Postoperatively, renal failure in both children was managed by continuous arteriovenous hemofiltration (CAVH). One child survived; the other died of sepsis. Serum lactate levels, which were 10 to 15 times the normal levels in both infants postoperatively, decreased rapidly in the survivor, but never approached normal levels in the infant who died. Although the best prospect for survival in neonatal NF remains prompt, radical, surgical excision and is associated with a low threshold for repeat debridement, modern supportive measures (including CAVH) may enhance survival. PMID- 8370015 TI - Thrombolytic therapy in peripheral arterial occlusive disease: mechanisms of action and drugs available. AB - Catheter-directed thrombolytic therapy has become an important part of the treatment of patients with acute arterial and graft occlusion. The underlying pharmacologic principle is the activation of plasminogen, bound to fibrin within the thrombus. Guide-wire passage reliably predicts success of catheter-directed thrombolysis. The underlying disease process leading to thrombosis should be accurately identified and promptly corrected to reduce the probability of recurrent occlusion. Streptokinase (SK), urokinase (UK) and recombinant tissue plasminogen activator (rt-PA) are the three agents used to treat peripheral arterial occlusive disease. The evolution from SK to UK and rt-PA and improvements in techniques and delivery systems have led to improved success rates and lower complication rates. Patient selection, basic technical considerations and overall results are discussed here. The currently available thrombolytic agents, as well as those being developed, are reviewed to provide background information for current and future applications. PMID- 8370016 TI - Arterial diagnosis and management of acute thrombosis of the lower extremity. AB - Acute ischemia of the lower extremity is associated with reduced blood flow to muscle, nerve, subcutaneous tissue and skin. This condition may be caused by thrombosis on an atherosclerotic plaque or embolus or by the occlusion of a previously placed arterial bypass graft. The difficulties in differentiating embolic arterial occlusion from acute thrombotic arterial occlusion are discussed. Although balloon catheter thrombectomy has been the traditional approach to treatment of patients with acute ischemia, this method has several disadvantages: it may not remove all of the thrombus, the thrombus may be inaccessible, it may damage vessels and atherosclerotic plaque and it does not identify or correct the underlying cause of the thrombosis. The advantages of catheter-directed thrombolysis are discussed, including its use as a diagnostic tool. Detailed techniques are presented along with data from extensive studies. PMID- 8370017 TI - Intraoperative thrombolysis in peripheral arterial occlusion. AB - Thromboembolic occlusion of peripheral arteries continues to be associated with significant morbidity, mortality and loss of limbs. Surgical intervention with prompt revascularization by clot extraction, alone or in combination with arterial bypass, remains the standard therapy for critical ischemia with imminent tissue loss. Mechanical thrombectomy using a balloon catheter has been the preferred technique for distal embolus or thrombus extraction. Unfortunately, complete thrombectomy is rare, and the procedure is associated with arterial wall injury. Intraoperative thrombolytic therapy is an attractive adjunct to catheter thrombectomy alone and is appropriate in the care of a significant number of patients with acute limb ischemia. Its safety and efficacy have been confirmed in the laboratory and in a limited number of patients. The authors review experimental and clinical data and report their experience with 19 patients. PMID- 8370018 TI - Thrombolytic therapy for deep venous thrombosis: a clinical review. AB - Although anticoagulation is the treatment most commonly chosen for patients suffering from deep venous thrombosis (DVT), thrombolytic therapy offers the promise of dissolving the thrombus within the deep venous system, restoring patency and preserving valve function. If this is achieved, the incidence and severity of post-thrombotic syndrome can be reduced. Data from 13 studies comparing anticoagulant therapy with thrombolytic therapy for DVT in 591 patients have shown that, among those treated with heparin, 4% had significant or complete lysis, 14% had partial lysis and 82% failed to improve or worsened. Of those receiving lytic therapy, 45% had significant or complete lysis, 18% had partial lysis and 37% failed to improve or worsened. Long-term follow-up of randomized patients has shown that those with successful lysis had a lower incidence of post thrombotic syndrome and improved long-term venous function. The failure rate of systemic lytic therapy among patients suffering iliofemoral venous thrombosis is high; therefore, catheter-directed thrombolysis has been adopted with increasing success. Thrombolytic therapy, delivered systemically using catheter-directed techniques, should be considered as an important alternative in the treatment of patients with DVT. PMID- 8370019 TI - Long-term results of treatment for axillary subclavian vein thrombosis. AB - Thrombolytic therapy is an effective method for reopening an occluded venous segment, but little is known about the long-term results of thrombolysis via direct intravenous route for axillary subclavian vein thrombosis (ASVT). Our experience with 13 cases of primary ASVT illustrates the possible advantages of a protocol consisting of lytic therapy, surgical decompression and percutaneous balloon angioplasty if a high-grade stenosis persists. If accompanied by adjunctive therapy to correct the underlying cause, thrombolytic therapy for ASVT results in acceptable long-term symptom relief and vein patency. PMID- 8370020 TI - Thrombolysis in peripheral arterial graft occlusion. AB - Acute thrombosis of arterial bypass grafts in the lower extremities poses a significant risk for limb loss. Graft salvage in patients affected by this complication remains a challenge. The vascular surgeon must consider the spectrum of treatment options (thrombolysis, thrombectomy, graft replacement) in managing acute graft thrombosis. Oral anticoagulants should be considered in patients with low-flow polytetrafluoroethylene (PTFE) grafts and after successful thrombolysis, with or without revision. The role of thrombolytic therapy for occluded vein grafts is less clear, but successful lysis is likely in patients who present within 48 hours of graft thrombosis and the etiology includes a correctable graft stenosis. PMID- 8370021 TI - Synthesis of multivalent beta-lactosyl clusters as potential tumor metastasis inhibitors. AB - A beta-lactosyl residue was linked to the amino groups of L-lysyl-L-lysine through spacer arms of three different lengths (C2, C4, and C9) to give trivalent beta-lactosyl clusters in order to increase the inhibitory activity of the beta lactosyl group against tumor cell colonization. Thus, O-(2,3,4,6-tetra-O-acetyl beta-D-galactopyranosyl)-(1-->4)-2,3, 6-tri-O-acetyl-glucopyranosyl trichloroacetimidate was treated with methyl or benzyl hydroxyethanoate, methyl or benzyl 4-hydroxybutanoate, and methyl 9-hydroxynonanoate, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate to give the corresponding beta-lactosides. These were coupled to L-lysyl-L-lysine, after conversion to the N-hydroxysuccinimide esters, to yield the corresponding trivalent beta-lactosyl-L lysyl-L-lysine conjugates in good yields. The beta-lactosyl group with a C4 spacer arm was also coupled similarly to poly(L-lysine) (M(r) 3800) to form a polyvalent beta-lactosyl cluster. Coinjection of the trivalent (with C2 and C4 spacer arms) and polyvalent beta-lactosyl clusters with the highly metastatic B16 murine melanoma cells inhibited the formation of lung colonies in C57/BL mice, whereas the trivalent cluster with a C9 spacer arm displayed no activity. PMID- 8370022 TI - [Carbohydrate building blocks for the construction of tumor-associated antigens. Synthesis of Lewis Y determinants]. AB - The synthesis of the ethoxycarbonyloctanyl glycoside of the Lewis-Y (Ley) tetrasaccharide, a part of complex glycosphingolipids, was based on the trichloroacetimidate method for glycoside synthesis. The regioselective introduction of protective groups and the high yield of epimers of the azidonitration reaction applied to O-[2,3,4-tri-O-acetyl-6-O-[dimethyl-(2,3 dimethyl-2-butyl)silyl]-beta-D- galactopyranosyl]-(1-->4)-3-O-acetyl-1,5-anhydro 6-O-[dimet hyl-(2,3- dimethyl-2-butyl)silyl]-D-arabino-hex-1-enitol led to a lactosamine acceptor molecule. The double specific introduction of an alpha-L fucosyl group in high yield gave a protected Ley-tetrasaccharide. After activation to give the alpha-trichloroacetimidate, specific beta-glycosylation with 8-ethoxycarbonyl octanol under SN 2 condition, followed by cleavage of all protective groups led to the tetrasaccharide, alpha-L-Fucp-(1-->2)-beta-D-galp-(1 ->4)-[alpha-L-fucp-(1--> 3)]-beta-D- GlcpNAcO(CH2)8CO2Et in high yield. PMID- 8370024 TI - Convergent synthesis of an elusive hexasaccharide corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococcus group A. AB - A convergent synthesis of a hexasaccharide corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococcus Group A is described. The strategy relies on the preparation of a key linear trisaccharide unit beta-D GlcpNAc-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap which has previously resisted our efforts. The trisaccharide functions both as a glycosyl acceptor and donor to give an elusive hexasaccharide. This fully functionalized unit can serve, in turn, as a glycosyl acceptor or donor for the synthesis of higher-order structures. Deprotection gives a hitherto unknown hexasaccharide for use as a hapten in immunochemical studies. The characterization of all compounds by high resolution 1H and 13C NMR spectroscopy is also described. PMID- 8370023 TI - Preparation of 4,6-cyclo-hexopyranoses by palladium-mediated intramolecular cyclodehalogenation. AB - 4,6-Cyclo-4,6-dideoxy-hexapyronoses were obtained by palladium-mediated intramolecular cyclodehalogenation. Thus, methyl 2,3-di-O-acetyl-4,6-dideoxy-4,6 diiodo-beta-D-galactopyranoside (3) afforded methyl 2,3-di-O-acetyl-4,5-cyclo-4,6 dideoxy-beta-D-galactopyranoside (5) in 56% yield upon treatment with hydrogen in the presence of palladium-on-charcoal and diethylamine. The structure of 5 was proven by MS, NMR including NOE measurements, and by independent conversion of 4 to 5 by zinc-mediated Wurtz synthesis. Similarly, methyl 2,3-di-O-acetyl-4,6 cyclo-4,6-dideoxy-alpha-D-galactopyranoside (6) and O-(2,3,-di-O-acetyl-4,6-cyclo 4,6-dideoxy-alpha-D-galactopyranosyl)-(1-- >4)-1,2,3,6-tetra-O-acetyl-beta-D glucopyranose (17) were obtained along with the respective 4,6-dideoxy analogues. Also methyl 2,3-di-O-acetyl-4,6-dideoxy-4,6-diiodo-beta-D-glucopyranoside (19) gave galacto-configured 5 stereoselectively. PMID- 8370025 TI - On the structure of calonyctin A, a plant growth regulator. AB - The plant growth regulator calonyctin A, isolated from the dried leaves of Calonyction aculeatum L. House (Yue-Guang-Hua), was separated into two pure components by high performance liquid chromatography. By use of mass spectrometry based on various ionization techniques, one- and two-dimensional NMR spectroscopy, IR spectrometry, and chemical methods the molecular structures of the two homologous glycosides were determined. Each molecule contains two hydroxy fatty acid residues and four 6-deoxyhexose units. The fatty acids are 3-hydroxy-2 methylbutanoic acid and 11-hydroxytetradecanoic acid or 11-hydroxyhexadecanoic acid. The 6-deoxyhexose residues (three of quinovose and one of rhamnose) comprise a tetrasaccharide having the following structure: [formula: see text] The long-chain hydroxy acid is linked glycosidically through its O-11 to Qui D and esterified to O-2 of Qui C, forming a macrocyclic lactone. The 3-hydroxy-2 methylbutanoic acid is ester-linked to O-3 of Qui C. PMID- 8370026 TI - Structure of an extracellular polysaccharide produced by Erwinia chrysanthemi. AB - Erwinia chrysanthemi pv zeae strain SR260, a phytopathogen of corn, produced from lactose an acidic extracellular polysaccharide which was purified and found to consist of L-rhamnose, D-mannose, D-glucose, and D-glucuronic acid in the ratio of 3:1:1:1. A combination of chemical (carboxyl-group reduction, methylation analysis, periodate oxidation, Smith degradation, and lithium-ethylenediamine degradation) and physical (1 and 2D NMR spectroscopy) methods revealed that the polysaccharide is composed of a hexasaccharide repeating unit 1: [formula: see text] PMID- 8370027 TI - Structural studies of acetan, an exopolysaccharide elaborated by Acetobacter xylinum. AB - The exopolysaccharide acetan, elaborated by Acetobacter xylinum, has been investigated. The polysaccharide and a heptasaccharide, obtained on enzymic hydrolysis, corresponding to the repeating unit were characterised by sugar and methylation analysis and by NMR spectroscopy and MS. It is concluded that the polysaccharide is composed of repeating units with the following structure. [formula: see text] The polysaccharide further contains approximately two O acetyl groups per repeating unit, which have not been assigned, but it appears that they are on primary locations. PMID- 8370028 TI - Structural studies of the capsular polysaccharide (S-21) from Klebsiella pneumoniae ATCC 31314. AB - The structure of the polysaccharide (S-21) elaborated by Klebsiella pneumoniae ATCC 31314 has been investigated. NMR spectroscopy, sugar and methylation analysis, uronic acid degradation, and partial hydrolysis to oligosaccharides were the main methods used. In order to obtain good NMR spectra, the polymer was subjected to non-specific degradation by treatment with fuming hydrochoric acid. It is concluded that S-21 is composed of pentasaccharide repeating units with the following structure. [formula: see text] Approximately 0.7 equivalent of O-acetyl group, distributed over at least three positions, was also present but not located. The carbohydrate backbone in S-21 is identical to that of Klebsiella K30 and K33 capsular polysaccharides. PMID- 8370029 TI - Recognition of the acceptor beta-D-GlcpNAc-(1-->2)-alpha-D-Manp- (1-->6)-beta-D Glcp-OR by N-acetyl-glucosaminyltransferase-V: none of the hydroxyl groups on the Glc-residue are important. AB - The enzyme, N-acetylglucosaminyltransferase-V (GlcNAcT-V, E.C. 2.4.1.155), transfer a beta-D-GlcpNAc residue, from UDP-GlcNAc, to the OH-6 group of the Man residue in the synthetic acceptor beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->6) beta-D-Glcp-O(CH2)7 CH3 (3). Trisaccharide 3 is an excellent substrate for the enzyme from hamster kidney with a Km value of 26 microM. In this paper we examine the contribution of the Glc residue in 3 to acceptor recognition by this enzyme. beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-O(CH2)7CH3 where the Glc residue in 3 has been deleted, was synthesized and found to be a very poor substrate with a Km value elevated to almost 2 mM. Two other analogues of 3, where the Glc residue was O-trimethylated (6) or O-tribenzylated (7), respectively, possessed Km values very near to those of 3. The Glc residue in 3 is thereby shown to present an important recognition element for GlcNAcT-V, but none of the free hydroxyl groups are required. This observation should facilitate the design of more hydrophobic and membrane-permeable analogues of 3 that are expected to function as specific glycosylation inhibitors. PMID- 8370030 TI - Complete assignment of the 1H NMR spectra of phytoalexin elicitor-active oligoglucosides. PMID- 8370031 TI - Identification of oligosaccharides consisting of D-glucuronic acid and L-glycero D-manno- and D-glycero-D-manno-heptose isolated from Vibrio parahaemolyticus O2 lipopolysaccharide. PMID- 8370032 TI - Occurrence of 2-O-sulphated D-glucuronic acid in rat liver heparan sulphate. PMID- 8370033 TI - Authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,5-anhydro-D-fucitol. AB - Described herein is an efficient method for the synthesis of the eight positional isomers of methylated and acetylated or benzoylated 1,5-anhydro-D-fucitol. The compounds are generated simultaneously by partial methylation of 1,5-anhydro-D fucitol and subsequent benzoylation, and the individual isomers are obtained in pure form by high-performance liquid chromatography. Debenzoylation of the latter and acetylation yielded the desired acetates. Reported herein are the 1H NMR spectra of the benzoates and the electron-ionization mass spectra of the acetates and the tri-O-methyl derivative. Also reported for the acetates and the tri-O methyl derivative are their linear temperature programmed gas-liquid chromatography retention indices on three different capillary columns. PMID- 8370034 TI - Synthesis of 3-deoxyaldulosonic acid esters by one-carbon chain extension of glycal-derived lactone precursors. AB - A convenient preparative route is described for 3-deoxyaldulosonic acids. Glycal precursors are oxidatively converted into 2-deoxyaldonolactones, which react with 1,3-dithian-2-yl anion to afford 1,3-propanediyl dithioacetals of higher 3 deoxyaldosuloses. Deprotection with mercuric salts in wet or dry alcohols gave high yields of the corresponding alkyl aldulosonates. Preparative reaction conditions were optimized and the anomeric configurations of the ketopyranose products were established by 13C NMR. PMID- 8370035 TI - Synthesis of the monodeoxy derivatives of 2-(trimethylsilyl)ethyl beta-lactoside. AB - Monodeoxy derivatives of 2-(trimethylsilyl)ethyl (Me3SiEt) beta-lactoside were synthesized, by deoxygenation at the disaccharide level, for the 2'-, 3'-, 4'-, and 6'-monodeoxylactosides. The 2-, 3-, and 6-deoxy derivatives were synthesized by beta-D-galactosylation of suitably protected monodeoxygenated Me3SiEt glucosides. Silver silicate was shown to be an efficient glycosylation promoter in the preparation of the 2- and 3-deoxylactosides. PMID- 8370036 TI - Synthesis of Kdo-alpha-glycosides of lipid A derivatives. AB - The synthesis of the lipopolysaccharide fragment O-(4,5,7,8-tetra-O-acetyl-3 deoxy-N-methyl-alpha-D-manno-2- octulopyranosylonamide)-(2-->6)-O-(2-deoxy-2 [(3R)-3- dodecanoyloxytetradecanamido]-4-O- phosphono-3-O-tetradecanoyl-beta-D glucopyranosyl)-(1-->6)-1-O-acetyl-2- deoxy-2 - [(3R)-3 dodecanoyloxytetradecanamido]-3-O-tetradecanoyl-alpha-D- glucopyranose (35 alpha) is performed via anomeric O-alkylation. With this objective, the 2-azido-3-O benzyl-2-deoxy-6-O-trifluoromethanesulfonyl-beta-D-glu copyranosides 5, 7, and 19 alpha, beta were synthesized from D-glucal and employed as alkylating agents. Reaction of 5 with the O-cyclohexylidene-protected Kdo-derivative 10 afforded the desired alpha-linked disaccharide, tert-butyldimethylsilyl 4-O-allyl-2-azido-3-O benzyl-2-deoxy-6- O-(4,5:7,8-di-O-cyclohexylidene-3-deoxy-N-methyl-alpha-D-manno 2- octulopyranosylonamide)-beta-D-glucopyranoside (11); even better yields of the structurally related disaccharide 12 were obtained with the 4-O-unprotected 7 as alkylating agent. 1-O-Desilylation of 12 furnished the lactol 20, which could be alkylated at the anomeric position with 1-O-allyl protected alkylating agents 19 alpha and 19 beta, both of which furnished exclusively the desired beta-(1-->6) linked trisaccharides allyl O-(4,5:7,8-di-O-cyclohexylidene-3- deoxy-N-methyl alpha-D-manno-2-octulopyranosylonamide)-(2-->6)-O-( 2-azido-3- O-benzyl-2-deoxy beta-D-glucopyranosyl)-(1-->6)-2-azido-3, 4-di-O-benzyl-2-deoxy-alpha- (21 alpha) and -beta-D-glucopyranoside (21 beta), respectively. Phosphorylation with diphenyl phosphorochloridate, replacement of the O-cyclohexylidene protective group by O-triethylsilyl (TES) protective groups, removal of the 1-O-allyl group, azido group reduction, subsequent N-acylation, and then O-acetylation provided the key 1-O-acetyl protected intermediate 30 alpha. Removal of the O-TES groups, subsequent O-acetylation, and hydrogenolytic O-debenzylation furnished O-[4,5:7,8 tetra-O-acetyl-3-deoxy-N-methyl-alpha-D-manno-2- octulopyranosylonamide]-(2-->6) O-(2-deoxy-4-O-diphenoxyphospho ryl-2-[(3R)- 3-dodecanoyloxytetradecanamido]-beta D-glucopyranosyl)-(1-->6)-1-O -acetyl-2- deoxy-2[(3R) dodecanoyloxytetradecanamido]-alpha-D-glucopyranose (33 alpha), which underwent the required selective O-tetradecanoylation at the 3-O- and 3'-O-position, thus furnishing, after hydrogenolytic O-dephenylation of the diphenoxyphosphoryl group, the target molecule 35 alpha. PMID- 8370037 TI - Synthesis of the methyl glycosides of a tri- and a tetra-saccharide related to heparin and heparan sulphate. AB - The methyl glycoside of a tetrasaccharide isolated from heparin, methyl O-(alpha L-idopyranosyluronic acid)-(1-->4)-O-(2-acetamido-2-deoxy-alpha-D- glucopyranosyl)-(1-->4)-O-(beta-D-glucopyranosyluronic acid)-(1-->3)-O-beta-D galactopyranoside disodium salt and a trisaccharide derivative thereof, methyl O (alpha-L-idopyranosyluronic acid)-(1-->4)-O-(2-acetamido-2- deoxy-alpha-D glucopyranosyl)-(1-->4)-O-beta-D-glucopyranosyluronic acid disodium salt, were synthesized using a block-type strategy. A suitable protected disaccharide block of iduronic acid and glucosamine (IdoA-GlcN) was used as a key intermediate for the syntheses and was glycosidated with a protected galactose derivative and a disaccharide block of glucuronic acid and galactose (GlcA-Gal) to give tri- and tetra-saccharide derivatives, respectively. Deprotection gave the target compounds. PMID- 8370038 TI - Synthetic approaches to 2-deoxyglycosyl phosphates. AB - By the use of the N-iodosuccinimide (NIS)-procedure, various glycals could be converted into 2-deoxy-2-iodoglycosyl phosphates. Treatment of glycals 1 and 7 with NIS and dibenzyl phosphate gave the corresponding alpha-1,2-trans-diaxial 2 deoxy-2-iodoglycosyl phosphates 2 and 8 as the main products. The beta-1,2-trans diequatorial compounds 3 and 9 were isolated as by-products. Analogous reaction of glycals 4 and 10 gave the corresponding 2-deoxy-2-iodoglycosyl phosphates 5, 6, 11, and 12 as crude products, which were characterized by 1H NMR spectroscopy. Classical phosphorylation of 2-deoxy-glycosyl chlorides 14 and 16 with silver dibenzyl phosphate gave the corresponding dibenzyl 2-deoxy-alpha-glycosyl phosphates 15 and 17. Alternatively, glycosylation of tri-O-acetyl-D-glucal using dibenzyl phosphate and triphenylphosphine hydrobromide afforded 15 in lower yield. The application of S-(2-deoxyglycosyl) phosphorodithioates as glycosyl donors provided the most convenient way to dibenzyl 2-deoxyglycosyl phosphates. The alpha-glycosyl phosphates 15, 20, and 22 could be synthesized by reaction of the 2-deoxyglycosyl dithiophosphates 18, 19, and 21 with dibenzyl phosphate and activation by iodonium di-sym-collidine perchlorate. Similarly, the 2,6 dideoxyglycosyl dithiophosphates 23 and 25 gave the 2,6-dideoxy phosphates 24 and 26; however, the isolation of these labile compounds could not be effected. PMID- 8370039 TI - "Chitin Leash": a polysaccharide heterobifunctional cross-linking agent which can be cleaved by lysozyme. AB - 6-O-[(2-Hydroxyethyl)poly(2-oxyethyl)]chitosan ("glycolchitosan") was oxidatively cleaved with nitrous acid and then partly acetylated with acetic anhydride, reacted with bromoacetyl-N-hydroxysuccinimide, and reacted further with acetic anhydride. Conditions were selected, including fractionation by size-exclusion chromatography, so that the resulting "Chitin Leash" had an estimated, average molecular weight of 10,000 (dextran standards), corresponding to a length of approximately 40 sugar residues. It possessed 0.9 terminal aldehyde and 2.6 random (presumably) side-chain bromoacetyl reactive groups per chain (average values). As a model system, the Chitin Leash was used to crosslink staphylococcal nuclease (SNase) to ribonuclease A (RNase) with retention of 75 and 78%, respectively, of the starting enzyme activities. For this coupling, the Nase was first converted to a sulfhydryl SNase derivative which retained 74% of the activity of starting enzyme. The yields in this synthesis were: 13% Chitin Leash from glycolchitosan, 24% Chitin Leash-RNase from Chitin Leash and 45% SNase Chitin Leash-RNase from the latter conjugate. The ratio of SNase to RNase in this conjugate was 1.0:0.94. In a second preparation, in which [14C]acetic anhydride was used, a longer reaction time was employed for the coupling of Chitin Leash to RNase. This gave a 1.0:1.8:0.95 molar ratio of Nase: [14C]Chitin Leash: RNase, revealing multiple attachment of the [14C]Chitin Leash to RNase. The activity of the RNase in the final conjugate was 20%. The latter conjugate was approximately 70% hydrolyzed by diaminooctyl-succinyl-lysozyme, disconnecting the two enzymes while not affecting their activities. PMID- 8370040 TI - Structure of the K10 capsular antigen from Escherichia coli O11:K10:H10, a polysaccharide containing 4,6-dideoxy-4-malonylamino-D-glucose. AB - The K10 antigen from Escherichia coli O11:K10:H10 consists of equimolar amounts of rhamnose and 4,6-dideoxy-4-malonylaminoglucose [Qui4NMal; 4-(2 carboxyacetamido)-4,6-dideoxyglucose]. Methylation analysis and 1 and 2D NMR spectroscopy showed that the K10 capsular polysaccharide has the structure [formula: see text] PMID- 8370041 TI - Structural elucidation of the capsular polysaccharide of Escherichia coli serotype K101 by high resolution NMR spectroscopy. PMID- 8370042 TI - Structural studies of the extracellular polysaccharide from Butyrivibrio fibrisolvens strain X6C61. AB - The capsular polysaccharide from Butyrivibrio fibrisolvens strain X6C61 has been investigated using NMR spectroscopy, mass spectrometry, methylation analysis, and partial acid hydrolysis as the main methods. The polysaccharide is composed of hexasaccharide repeating units having the following structure. [formula: see text] The polysaccharide also contains O-acetyl groups, of which approximately 70% are substituted to O-3 of the beta-D-Glc pA residue. PMID- 8370043 TI - Structural studies of the saccharide part of the cell envelope lipopolysaccharide from Haemophilus influenzae strain AH1-3 (lic3+). AB - The structure of the saccharide part of the lipopolysaccharide from Haemophilus influenzae strain AH1-3 (lic3+) has been investigated. The saccharide was obtained from the lipopolysaccharide by mild acid hydrolysis followed by high performance anion-exchange chromatography, and isolated fractions were studied by methylation analysis, NMR spectroscopy, and FAB mass spectrometry. The major saccharide is a heptasaccharide with the following structure, [formula: see text] in which Kdo is 3-deoxy-D-manno-oct-2-ulosonic acid and PEA is 2-aminoethyl phosphate. Hep is identified as L-glycero-D-manno-heptose. The absolute configuration of the phosphorylated heptose is tentative only. PMID- 8370044 TI - Short synthesis of allyl 2-acetamido-2-deoxy-3,6-di-O-(alpha-L-fucopyranosyl) beta-D-glucopyrano side. PMID- 8370046 TI - A synthetic approach to polysialogangliosides containing alpha-sialyl-(2-->8) sialic acid: total synthesis of ganglioside GD3. AB - A stereocontrolled, facile total synthesis of ganglioside GD3 is described as an example of a proposed systematic approach to the preparation of gangliosides containing an alpha-sialyl-(2-->8)-sialic acid unit alpha-glycosidically linked to O-3 of a D-galactose residue in their oligosaccharide chains. Glycosylation of 2-(trimethylsilyl)ethyl 6-O-benzoyl-, 3-O-benzoyl-, or 3-O-benzyl-beta-D galactopyrano-sides, or 2-(trimethylsilyl)ethyl 2,3,6,2',6'-penta-O-benzyl-beta lactoside (7), with methyl [phenyl 5- acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O acetyl-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylono-1',9 lactone)- 4,7-di-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyrano sid] onate (3), using N-iodosuccinimide-trifluoromethanesulfonic acid as a promoter, gave the corresponding alpha glycosides 8 (32%), 13 (33%), 14 (48%), and 17 (31%), respectively. The glycosyl donor 3 was prepared from O-(5-acetamido-3,5-dideoxy-D glycero-alpha-D-galacto-2-nonulopyranosy lonic acid)-(2-->8)-5-acetamido-3,5- dideoxy-D-glycero-D-galacto-2-nonulopyranosonic acid by treatment with Amberlite IR-120 (H+) in methanol, O-acetylation, and subsequent replacement of the anomeric acetoxy group with phenylthio. Compound 8 was converted into the methyl beta-thioglycoside via O-benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group by reaction with methylthiotrimethylsilane. Compound 17 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the alpha-trichloroacetimidate, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol to give the beta glycoside. This glycoside was easily transformed, via selective reduction of the azido group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester and lactone functions, into ganglioside GD3. PMID- 8370045 TI - Chemical behavior of benzylidene acetal groups bridging the contiguous glucose residues in malto-oligosaccharide derivatives. AB - Treatment of phenyl alpha-maltoside with an excess of alpha, alpha dimethoxytoluene in the presence of (+)-10-camphorsulfonic acid, followed by partial hydrolysis to remove unstable acyclic acetal substituents, gave phenyl 3,2':4',6'-di-O-benzylidene-alpha-maltoside. Thus, one of the benzylidene groups formed an eight-membered cyclic acetal ring bridging the two monosaccharide components. This acetal function was stable under conventional acylation and alkylation conditions, but was selectively hydrolyzed by 80% acetic acid at room temperature. Treatment of a per-O-benzoyl derivative of 1 with N-bromosuccinimide barium carbonate afforded phenyl 2,6,3', 4'-tetra-O-benzoyl-6'-bromo-6'-deoxy alpha-maltoside in 80% yield. Reductive ring opening of the tri-O-benzyl derivative of 1 with lithium aluminum hydride-aluminum chloride gave a 2,3,6,3',4'-penta-O-benzyl derivative, while reduction with sodium cyanoborohydride-hydrogen chloride or borane trimethylamine complex-aluminum chloride afforded a 2,3,6,3',6'-penta-O-benzyl derivative in good yield. Similar regioselectivity was observed in the reductive cleavage of a 1,6-anhydro 3',2'':4'',6''-di-O-benzylidene-beta- maltotriose derivative. PMID- 8370047 TI - Solid-phase synthesis and conformational studies of glycosylated derivatives of helper-T-cell immunogenic peptides from hen-egg lysozyme. AB - 3-Mercaptopropionic acid and N alpha-Fmoc serine, both with unprotected carboxyl groups, were stereospecifically glycosylated in 62-82% yields, using saccharide 1,2-trans peracetates and Lewis acid catalysis. The resulting glycosylated building blocks were used in the synthesis of derivatives of helper-T-cell stimulating peptides, with the carbohydrate moiety located at the amino terminus, or internally in the peptide chain. 1H NMR spectroscopy in Me2SO-d6 showed that the glycopeptides assumed random conformations, which were not influenced by the glycosylation or by single substitutions of amino acids in the peptide moiety. PMID- 8370048 TI - [The genetics of sex]. AB - A stepwise resolution of the role of individual genes known to play role in sex determination is presented. Cytogenetic abnormalities e.g. male phenotype with XX and female phenotype with XY gonosomal complements helped substantially to ascertain SRY (Sex region of Y) gene activity to be essential for sex phenotype development control. This control seems to be rather suppressive than activating. PMID- 8370049 TI - [Maladaptation and the circumstances of its development]. AB - In the submitted review the author discusses contemporary views on the maladaptation syndrome. He characterizes mental stress and conditions under which it develops and ways in which individuals can react, as well as differences in the reaction of children, adolescents and adults. The author characterizes maladaptation, explains causes of its development and manifestations in relation to age (child, adolescent, adult) and its possible sequelae. Finally the paper contains reflections on the possible prevention of influences which may lead to maladaptation behaviour. PMID- 8370050 TI - [Candida sepsis. I. Risk factors, pathogenesis and the clinical picture]. AB - Candida sepsis is a serious and ever increasing complication in patients with a reduced defense capacity. At the intensive care unit of the infectious department in 1978-1990 from a total of 430 patients with the diagnosis of sepsis 20 (4.7%) had a Candida aetiology. Candida sepsis is suspected in particular in leukaemic patients with neutropenia, in organ transplantations and in patients given intensive care on account of a serious primary disease, bacterial infection or after surgery. The risk of deep candidosis is increased by venous catheters, hyperalimentation, antibiotic treatment, invasive operations. Diagnosis is supported by endophthalmitis and skin lesions; signs of affection of the liver, lungs, kidneys and cardiac valves are sought. Analysis of risk factors, pathogenesis and the clinical picture of invasive Candida infections is based on ample data in the literature. PMID- 8370051 TI - [Candida sepsis. II. Laboratory methods and their clinical importance]. AB - The authors present experience assembled at the septic station of the infectious department and mycological laboratory as regards interpretation of results of laboratory examinations in invasive Candida infections and they summarize the most important data from the literature on the correct collection of material, evaluation of microscopic and cultivation findings, the importance of examinations and haemocultures, venous catheters, urine, faeces and sputum. They analyze problems of serological examination and direct detection of antigen, they recommend mycological monitoring of patients at risk. In the conclusion they summarize the most frequent mistakes as regards the evaluation of laboratory results and indications of treatment. PMID- 8370052 TI - [Surveillance of tuberculosis in the Czech Republic in 1991]. AB - They authors present an interim report on the epidemiological situation of tuberculosis and the effectiveness of control measures as regards tuberculosis in the Czech Republic in 1991. The data are compared with previous years. The incidence of tuberculosis of all forms was 19.9/100,000 population, TB of the respiratory organs 16.2/100,000 and the incidence of bacteriologically confirmed respiratory TB 11.5/100,000 population. As compared with previous years, no statistically significant differences were found. Extrapulmonary TB accounted for less than 10% of the incidence, the position was similar also as regards mycobacterioses other than TB. The incidence of TB in children was 1.3/100,000 children under 15 years, after a transient increase in 1990 (microepidemic in gypsy children), a marked decline was recorded. The TB mortality rate was low (1.1/100,000 population), the prevalence to the date of Dec. 31 1991 was 21.7/100,000 population. On account of complaints 76% new cases were detected, the majority within 1 month, antituberculous treatment was effective, the mean period of treatment was reduced to less than 8 months. However, long in-patient treatment persists usually at the beginning of antituberculous treatment (3 months). PMID- 8370053 TI - [Naftifin--laboratory and clinical experience with a new antimycotic from the allylamine group]. AB - The authors evaluated the effectiveness of naftifin on a broad spectrum of 42 types of agents causing mycoses. Using the microdilution method, the authors assessed minimal inhibiting concentrations (MIC) of this antimycotic agent in 107 clinical isolates. Naftifin displayed a selective antifungal activity: excellent sensitivity was found in dermatophytes (MIC 90% = 0.39 mg.l-1), Aspergillae were medium sensitive (MIC = 0.09-12.5 mg.l-1). The majority of yeasts and filamentous fungi from the group of Zygomycetes was resistant to naftifin. The therapeutic results in 57 subjects with dermatomycoses corresponded to the results of in vitro tests of the antimycotic agent. Most successful as treatment of dermatophytoses at extra-intertriginous sites and treatment of pityriasis versicolor; manifestation of candidoses were not affected. The commercial preparation used--Fetimin cream--is considered by the authors a suitable alternative of hitherto used local antimycotics, in particular preparations from the azole series. PMID- 8370054 TI - [A review of mushrooms containing amanitins and phalloidines]. AB - The toxic peptides amanitins and phalloidins were found in 22 species of gilled fungi in Europe: 3 species of the Amanita genus, 8 species of the Galerina genus and 11 of the Lepiota genus. Galerina sulcipes in the most toxic one, followed by Amanita phalloides, A. virosa, Galerina marginata and Lepiota brunneoincarnata. PMID- 8370055 TI - [Review of present knowledge on the pathogenesis and pathophysiology of Amanita phalloides poisoning]. AB - The mushroom poisoning of phalloid type is caused by amatoxins, mainly by alpha amanitine. It is a cytotoxin which acts through an indirect mechanism. It binds irreversibly the nucleolar enzyme, RNA-polymerase II in cells with intensive proteosynthesis (enterocytes in the digestive tract, hepatocytes in the liver and epithelial cells of proximal renal tubules). A tight binding of the toxin with the enzyme blocks the transcription from DNA to m-RNA and thus makes the proteosynthesis impossible. This results in the cell necrosis. Pathophysiology of the phalloid type poisoning is rather complicated, as the disorders of primarily affected organs (gastrointestinal tract, liver and kidney) produce a derangement of other remote organs and systems. After a relatively long period of latency (average 8-10 hours) the symptoms of the initial phase of the symptomatologic course of intoxication--excessive vomiting and diarrhea (during one or two days)- are observed, leading to dehydration which culminates in the hypovolemic shock. A short subsequent phase of an apparent improvement (in the 3rd day) is followed, beginning with the fourth day, by an acute failure of the liver and kidney. The cause of the failure of both the organs is the same--the toxic noxa. Therefore it is not possible to classify the coexistence of acute hepatal and renal failure as a so-called hepatorenal syndrome. The true hepatorenal syndrome is namely a potentially reversible prerenal failure accompanying a variety of serious liver diseases, namely in their terminal phase. The phalloid nephropathy, however, has two constituents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370056 TI - [Methods in laboratory diagnosis of Amanita phalloides poisoning]. AB - Methods for laboratory diagnostics that can be used in Amanita phalloides intoxication examinations are described and discussed. These methods (microscopic examination, chemical methods as TLC, HPTLC, HPLC, RIA, and clinico-biochemical examinations) are characterized, their use and limits, and the possibility of using during the treatment is emphasised. PMID- 8370057 TI - [Isolation of toxic peptides from Amanita phalloides and their analysis using high-performance liquid chromatography]. AB - The objective of the work is isolation of toxic peptides from Amanita phalloides- amatoxins (alfa-, beta-, gamma-amanitin) and phallotoxins (phalloidin, phallacidin, phallisin, phallisacin) by liquid chromatography on Sephadex LH-20 according to Yocum modification. Seven main toxins were isolated in centigram amounts. The purity of the toxins isolated was verified by the characteristics of their absorbance spectra, by thin layer chromatography (TLC) and high-performance liquid chromatography on reversed phase (RP-HPLC). The fraction of acid phallotoxins which appears homogenous in TLC and Sephadex LH-20 was separated into 5 substances (four of which are phallotoxins) by preparative RP-HPLC technique. The toxins isolated are sufficiently pure to be used as standards in HPLC. PMID- 8370058 TI - [Hemoperfusion in mushroom poisoning. Clinical analysis of 58 patients]. AB - Fifty-eight patients with acute mushroom poisoning--Amanita phalloides were treated. Among them were 28 children and 2 adolescents. From all the patients mean age was 30.5 years, 31 patients were in hepatic coma. All patients undergone conservative treatment and haemoperfusion. The mean time from beginning of acute poisoning to the first haemoperfusion was 61 hours. Ninety-eight haemoperfusions were performed, from this number 26 using Amberlite XAD-2. Seventeen simultaneous or subsequent haemodialyses and 12 plasmaphereses were performed. Mortality occurred in 20 patients (34.5%). Survival of patients depended on the amount of ingested mushroom, on the early admission of patients to dialysis centre and on the beginning of extracorporeal treatment until the period of 24 hours after acute poisoning. PMID- 8370059 TI - [Amanita phalloides toxins in dried mushrooms]. AB - The content of toxins from Amanita phalloides in dried carpophores is decreasing in the dependence on time. The content of alpha-amanitin found after 20 years was about one half. A mere trace of alpha-amanitin which is the most stable of all toxins was detected in a carpophore 50 years old. Degradation of amatoxins and phallotoxins by light (mainly the UV part) and high temperatures was observed. PMID- 8370060 TI - [Amanita phalloides poisoning queries recorded at the Toxicology Information Center in Prague]. AB - The Poison Information Centre answered in 1990 and 1991 in the mean 6000 inquiries year. Inquiries concerning mushrooms belong to the most severe ones, their number may be substantially different. In 1990 there were 38 inquiries regarding mushrooms, only 8 inquiries concerning Amanita phalloides, but in 1991 146 inquiries including 65 demanding symptoms and treatment of Amanita phalloides intoxication. In the same year 27 Amanita phalloides intoxications were confirmed on the basis of discharging reports from the hospitals, in seven cases fatal. As important prognostic factors seem the early visit of a physician and the treatment without delay. The influence of negative prognostic factors by Floersheim--short latency period, massive founding of spores and the lowering of the Quick test under 10% were not confirmed by the data of the Poison Information Centre. PMID- 8370061 TI - [Contempo '92]. PMID- 8370062 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 8370063 TI - The calcium signal in human neutrophils and its relation to exocytosis investigated by patch-clamp capacitance and Fura-2 measurements. AB - Intracellular calcium ([Ca2+]i) and exocytosis of human neutrophils were investigated with patch-clamp capacitance and Fura-2 fluorescence measurements. Intracellular application of GTP gamma S induces a calcium transient and exocytosis. The onset of degranulation occurs at the time where the maximal [Ca2+]i is reached. Despite the close correlation in time, buffering [Ca2+]i at the resting level or at approximately 2 microM leaves the extent and the time course of degranulation unchanged. The decay of the calcium transient is due to diffusional equilibration between the cytosol and the pipette volume. GTP gamma S activates no cellular mechanisms for Ca2+ reuptake or extrusion. The endogenous calcium buffer capacity can be estimated to be as low as that of approximately 90 microM Fura-2. Stimulation with fMLP also induces degranulation and a calcium transient. The decay of fMLP-induced calcium transients is much faster than that of GTP gamma S-induced transients and is independent of diffusion indicating that fMLP also induces rapid reuptake or extrusion of Ca2+. Degranulation but not the calcium transient requires the presence of intracellular GTP. Different signalling pathways appear to be involved in GTP gamma S- and fMLP-stimulated calcium signals. The intracellular calcium release is not an essential signal to initiate exocytosis in neutrophils. PMID- 8370064 TI - Calcium control on InsP3-induced discharge of calcium from permeabilised hepatocyte pools. AB - The control exerted by intralumenal and cytosolic Ca2+ on InsP3-induced release of Ca2+ from intracellular Ca2+ pools in suspensions of saponin-permeabilised rat hepatocytes was investigated by combined Quin-2 and 45Ca2+ measurements at 20 degrees C. We failed to detect a major effect of intralumenal Ca2+ in regulating this release, as various manipulations in which the load of the Ca2+ pools was varied by a factor of two did not significantly affect the apparent relative efficiency of InsP3 in releasing Ca2+; these manipulations included loading the Ca2+ pools up to various steady state levels by preliminary equilibration at various external free Ca2+ concentrations, as well as emptying them progressively through the blockade of pump-mediated Ca2+ uptake. As regards Ca2+ on the cytosolic side, in contrast with recent results obtained with other systems, we found that, at maximal doses, InsP3-induced Ca2+ release was not stimulated by raising Ca2+ from very low to submicromolar or micromolar concentrations, and that only relatively high concentrations of free Ca2+ inhibited this release (half-maximal inhibition was between 3 and 15 microM). Such elevated Ca2+ concentrations reduced the size of the InsP3-sensitive Ca2+ pool. We also noted that the apparent cooperativity of InsP3 activation of release at pCa 5 was noticeably less than that observed at pCa 7. As a result, at low InsP3 concentrations, a rise in cytosolic Ca2+ from pCa 7 to pCa 5 stimulated InsP3 mediated Ca2+ release. These results are discussed in the context of the current speculations about tissue specificity, heterogeneity, quantal release, oscillations, and the several different mechanisms that may control InsP3-induced Ca2+ release. PMID- 8370065 TI - Nimodipine protects cultured spinal cord neurones from depolarization-induced inhibition of neurite outgrowth. AB - In the nervous system calcium ions play a crucial role in the regulation of growth cone motility, cell migration and neurite outgrowth. High intracellular Ca2+ concentrations severely disturb Ca(2+)-regulated processes and may lead to neuronal death. We studied whether the Ca(2+)-antagonist nimodipine could prevent inhibition of neurite outgrowth which occurs in depolarized cultures of rat foetal spinal neurones. Spinal cord slices were depolarized in culture with 50 mM K+. Nimodipine (0.01-10 microM) was added before depolarization. After 5 and 7 days the effect of treatment was determined by: (a) blind scoring of neurite outgrowth under phase contrast; and (b) measuring neurofilament (NF) protein with an ELISA. Neurite outgrowth was markedly decreased after depolarization, but was restored to control values by nimodipine (0.1 microM). Depolarization also led to a decrease in total NF content (18%). The NF content of depolarized slices incubated with 0.1 microM nimodipine was the same as in the controls. Thus, depolarization-induced Ca2+ entry into spinal neurones inhibits neurite outgrowth from spinal neurones. Low concentrations of nimodipine prevented this inhibition. As nimodipine had no effect on neurite outgrowth in control cultures, we conclude that nimodipine does not act as a neurotrophic factor but rather as a neuroprotective agent. PMID- 8370067 TI - One-pool model for Ca2+ oscillations involving Ca2+ and inositol 1,4,5 trisphosphate as co-agonists for Ca2+ release. AB - Experimental observations indicate that Ca(2+)-induced Ca2+ release (CICR) may underlie Ca2+ oscillations in a variety of cells. In its original version, a theoretical model for signal-induced Ca2+ oscillations based on CICR assumed the existence of two types of pools, one sensitive to inositol 1,4,5-trisphosphate (IP3) and the other one sensitive to Ca2+. Recent experiments indicate that Ca2+ channels may sometimes be sensitive to both IP3 and Ca2+. Such a regulation may be viewed as Ca(2+)-sensitized IP3-induced Ca2+ release or, alternatively, as a form of IP3-sensitized CICR. We show that sustained oscillations can still occur in a one-pool model, provided that the same Ca2+ channels are sensitive to both Ca2+ and IP3 behaving as co-agonists. This model and the two-pool model based on CICR both account for a number of experimental observations but differ in some respects. Thus, while in the two-pool model the latency and period of Ca2+ oscillations are of the same order of magnitude and correlate in a roughly linear manner, latency in the one-pool model is always brief and remains much shorter than the period of oscillations. Moreover, the first Ca2+ spike is much larger than the following ones in the one-pool model. These distinctive properties might provide an explanation for the differences in Ca2+ oscillations observed in various cell types. PMID- 8370066 TI - The polyether Bistramide A affects the calcium sensitivity of the contractile proteins in frog atrial heart muscle. AB - The effects of Bistramide A, a new toxin isolated from the Urochordate Lissoclinum bistratum Sluiter have been studied on the mechanical activity of frog heart atrial muscle preparations. The peak tension of isolated trabeculae was sensitive to nanomolar concentrations of Bistramide A. Lineweaver-Burk relationships suggest that Bistramide A competes with Ca for a common site. In voltage-clamped trabeculae, the toxin inhibited both the cadmium-sensitive Ca current and the phasic component of the tension with a dissociation constant of 3.3 microM and a stoichiometry of 2. Bistramide A decreased the isometric tension of skinned fibres in a dose-dependent manner with a dissociation constant of 400 nM and a stoichiometry of 2. The toxin reduced the maximum Ca activated force and decreased the sensitivity of the contractile proteins to Ca. The data suggest that Bistramide A decreases the Ca-sensitivity of contractile proteins prior to blocking the Ca current. PMID- 8370068 TI - Identification of an S100 target protein: glycogen phosphorylase. AB - An S100 binding protein from skeletal muscle, R95 000, has been purified, identified as glycogen phosphorylase, and shown to be regulated in vitro by the S100 alpha isoform. When a soluble skeletal muscle fraction was subjected to a standard purification procedure for glycogen phosphorylase, R95 000 copurified with the 95 000 molecular weight glycogen phosphorylase protein standard on SDS polyacrylamide gels, as well as having glycogen phosphorylase activity. In addition, purified glycogen phosphorylase a and b interacted with both S100 isoforms, S100 alpha and S100 beta, by gel overlay and affinity chromatography. While S100 beta had no effect on the enzymatic activity of glycogen phosphorylase a, S100 alpha inhibited the enzymatic activity of glycogen phosphorylase a in a calcium-independent manner. Altogether, these data suggest that glycogen phosphorylase may be an intracellular S100 alpha target in skeletal muscle fibers. Furthermore, these results suggest that the inhibition of glycogen phosphorylase a activity may be responsible for the lack of fatigability of slow twitch fibers, which express S100 alpha, when compared to fast-twitch fibers, which do not express S100 proteins. PMID- 8370069 TI - Intracellular calcium transients induced by different kinds of stimulus during myogenesis of rat skeletal muscle cells studied by laser cytofluorimetry with Indo-1. AB - Resting intracellular calcium levels and intracellular calcium transients induced by three types of stimulus (acetylcholine, high potassium and caffeine) were recorded, during in vitro myogenesis, by means of a ratiometric fluorescence method using the calcium probe Indo-1 under laser illumination. Resting levels seemed to decrease with the age of cultured cells and the depolarization-induced transients, through 100 mM K+ or Ach application, were progressively faster and larger as the muscle cells developed. An additive mechanism, likely due to calcium entry into the cell through nicotinic acetylcholine receptors, could explain the differences observed in Ach-induced responses as compared with the 100 mM K(+)-induced ones. In myoballs (the older cells) the calcium transients exhibited progressively a biphasic shape. From data obtained in different conditions (tetrodotoxin, nifedipine, strontium and free Ca EGTA) and those indicating the appearance of caffeine-releasable intracellular calcium stores only at 2-3 days stage, and from the previously reported developmental appearance of calcium currents and contraction, it was proposed that, in young myotubes, the calcium transients were more dependent on extracellular calcium than in older cells. These developmental data are discussed in the light of a known model of the in situ biogenesis of the structures involved in excitation-contraction coupling (ECC) like transverse tubules and triads. PMID- 8370070 TI - Calbindin D28K expression in transfected mouse NIH3T3 cells. AB - Calbindin D28K (formerly known as vitamin D-dependent calcium binding protein and referred to here as calbindin) is found in a wide variety of tissues, but only in certain cells within those tissues. Apart from its ability to bind calcium, nothing is known about its function in these cells. To investigate its role we have transfected the chick calbindin cDNA into mouse NIH3T3 fibroblasts and established a new cell line where calbindin is permanently expressed. Immunofluorescence studies show that calbindin is distributed throughout the cytoplasm, and treatment of the cells with cycloheximide shows that it has a relatively long half-life within the cell. Measurements of intracellular calcium concentration using Fura-2 suggest that the presence of calbindin within the cells does not affect the increase in intracellular calcium levels which occurs in response to serum stimulation or the rate at which these return to the basal level, but that it may act as a buffer for the entry of extracellular calcium. PMID- 8370071 TI - Multiple derangements of cytokine homeostasis in mice infected with immunosuppressive retrovirus. AB - Altered production of various lymphokines is considered an important factor in retrovirus-induced immunosuppression. We have measured the production of interleukin 2 (IL-2), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-beta 1), and tumor necrosis factor alpha (TNF-alpha) in splenocytes of retrovirus-infected NMRI mice. In Con A-stimulated splenocytes from mice infected with the acute transforming retrovirus Friend leukemia complex (FLC), TNF-alpha and IL-6 production was significantly suppressed. We compared cytokine production in infection with Friend-derived murine immunosuppressive virus (Fd-MIV), a low oncogenic retrovirus that induces a immunosuppression of a magnitude similar to that of FLC. In Fd-MIV infection, the ability of lymphoid cells to produce both IL-2 and TNF-alpha was suppressed. The suppression of these cytokines coincided with the suppression of the primary antibody response. In contrast to FLC infection, the production of IL-6 was elevated. Furthermore, increased production of TGF-beta was found in unstimulated splenocytes from Fd-MIV-infected mice. Infection with immunosuppressive retroviruses induces a complex derangement of T cell cytokine homeostasis and the relative contributions of the various factors to the immunosuppressed state are difficult to assess at present. PMID- 8370072 TI - Bidirectional modulation of human B cell stimulation by activated T cells. AB - Although human T cells have been shown to exert effects of both help and suppression on B cells, the precise sequelae for these different effects have not yet been delineated. The present study therefore examined in detail the functions of human peripheral blood T cells activated for various periods by immobilized anti-CD3 to modulate B cell responses. CD4+ (CD45RA+ or CD45RA-) or CD8+ (CD45RA+ or CD45RA-) T cell subsets were cultured in wells with immobilized anti-CD3 for as long as 20 days. At various periods of time, these activated T cells were harvested and cocultured with either fresh resting B cells or preactivated B cells. CD4+ and CD8+ T cells, irrespective of their expression of the CD45RA molecule, were able to stimulate resting B cells to express transferrin receptor (CD71) and IL-2 receptor (CD25) up to 17 days after activation with immobilized anti-CD3, although CD8+ but not CD4+ T cell subsets appeared to become less potent in stimulating resting B cells after 17 days of activation. By contrast, these CD4+ and CD8+ T cell subsets activated by immobilized anti-CD3 suppressed the maturation of the B cells preactivated with anti-CD3-stimulated CD4+ T cells, at the same time as when they provided help for resting B cells. The suppression, but not the help, was abrogated by treatment of the T cells with mitomycin C up to 13 days after activation. The suppression was not abrogated by addition of exogenous IL-2, irrespective of the length of stimulation of suppressor-effector T cells. These results indicate that human activated T cells can provide help and suppression simultaneously, irrespective of their phenotypes. Moreover, the data suggest that the state of activation of B cells might be important in determining the functions of the activated T cells. PMID- 8370073 TI - Rat splenocytes inhibit antigen-specific lymphocyte proliferation through a reactive nitrogen intermediate (RNI)-dependent mechanism and exhibit increased RNI production in response to IFN-gamma. AB - Rat splenocytes inhibited antigen-specific proliferation of primed lymph node cells in vitro. This inhibition resided in the plastic-adherent splenocyte fraction and was radioresistant, suggesting that the effect was due to macrophages. While this suppression was more evident if spleen cells were derived from immunized rats, spleen cells from normal rats were just as suppressive when added to cocultures at higher numbers. Proliferative responses were greatly enhanced in the presence of NG-monomethyl-L-arginine, a specific inhibitor of the nitric oxide synthetic pathway, and significant levels of nitrite (NO2-), a product of this pathway, were detected in culture supernatants in association with suppressed responses, supporting the notion that suppression was mediated by the L-arginine-dependent production of reactive nitrogen intermediates (RNI). When the splenocytes were physically separated from the responding lymph node cell population, high levels of NO2- were still detected but proliferative responses were no longer inhibited, suggesting that cell proximity or contact is necessary for delivery of the suppressive signal. Adherent splenocytes cultured alone produced low levels of NO2-. Addition of 1 to 50 U/ml IFN-gamma induced a dose-dependent increase in NO2- production, with the maximal level approximating that found in suppressed cocultures; TNF-alpha, IL-2, or LPS did not synergize with IFN-gamma to enhance NO2- production. These findings suggest that by activating macrophages to upregulate RNI synthesis, IFN-gamma-producing T cells may exert a negative influence over their own proliferation. PMID- 8370074 TI - Adoptive transfer of experimental autoimmune dacryoadenitis in susceptible and resistant mice. AB - Strains of mice with diverse genetic backgrounds were compared for their ability to develop experimental autoimmune dacryoadenitis (EAD) after immunization with a purified lacrimal gland antigen (LG-Ag) in complete Freund's adjuvant. Susceptibility to the induction of EAD was linked to the murine H-2 histocompatibility background. SJL/J mice with the H-2s haplotype were the most susceptible to EAD, developing extensive cellular infiltration of the lacrimal gland, but those with the H-2d haplotype (BALB/c mice) or H-2q haplotype (DBA/J mice) were resistant to EAD, having little or no infiltration of the lacrimal gland. There was no correlation between the development of EAD and either the antibody response or the in vitro lymphocyte proliferative response to LG-Ag. The differences in the induction of EAD observed between susceptible and resistant strains resided in the different capacity of their lymphocytes to transfer disease. Splenocytes from susceptible SJL/J mice sensitized with LG-Ag in CFA could be activated in vitro with LG-Ag to transfer disease to normal syngeneic recipients. The capacity for adoptive transfer was abrogated by treatment with anti-Thy 1.2 antibody plus complement, an indication that T cells are responsible for the transfer of EAD. However, EAD cannot be transferred with the donor cells from resistant mice even after they have been cultured in vitro with LG-Ag. These results suggest that T cells play a major role in the induction of EAD and that variations in susceptibility are under the control of distinct genetically inherited mechanisms that may include active suppression. PMID- 8370075 TI - Studies of the cellular immune response to heparan sulfate proteoglycan in the tight skin mouse. AB - As in human scleroderma, tight skin (TSK/+) mice develop cutaneous hyperplasia with over-production of extracellular matrix, including collagen and proteoglycans, associated with autoimmunity to a number of autoantigens. The present study investigated the presence of cellular autoimmunity to basement membrane heparan sulfate proteoglycan (HSPG) in diseased TSK/+mice and their nondiseased littermates, pallid mice (+/pa). Lymphocyte proliferative responses to specific HSPG antigens, including intact HSPG, HSPG protein core (P. Core), and the glycosaminoglycan heparan sulfate (HS) were studied. Splenocytes from young TSK and control pallid mice reacted weakly to intact HSPG and HSPG P. Core antigens and did not respond to HS. However, lymphocytes from old TSK mice were reactive with HSPG and P. Core and demonstrated a de novo response to HS. The proliferative response to intact HSPG and HSPG P. Core in TSK mice was T cell dependent, but the response to HS was T cell independent. The T cell-dependent response was mediated by the CD4-positive subset and required the participation of class II major histocompatibility complex molecules. Cellular autoimmunity to HSPG, a critical cell surface and extracellular matrix component, may play a role in the disease suffered by TSK mice. Further studies are necessary to determine the mechanisms which link autoimmunity to HSPG with the pathology seen in TSK mice, particularly the overproduction of extracellular matrix and fibrosis. PMID- 8370076 TI - Chromium and tritiated thymidine releases from target cells are differential events in human monocyte/macrophage-mediated cytotoxicity. AB - Cytotoxic properties of human activated macrophages were investigated by measuring both 51Cr and [3H]TdR releases from prelabeled target cells. The kinetic study of macrophage-mediated cytotoxicity indicated that 51Cr and [3H]TdR releases showed a distinct time course. Next, when [3H]TdR release was measured as a parameter for cytotoxicity, pretreatment of activated macrophages with either actinomycin D or emetine remarkably decreased their cytotoxicity in a dose dependent manner. In contrast, the pretreatment with these inhibitors had little effect on 51Cr release. Furthermore, the addition of Zn2+ in the assay medium caused the decrease in [3H]TdR release but not 51Cr release from the target cells. Taken together, our findings indicate that 51Cr and [3H]TdR releases from the target cells are induced by activated macrophages through different cytotoxic mechanisms; the former does not require RNA and protein syntheses in macrophages during coculture, whereas the latter requires them. Our findings also suggest that macrophage-derived nuclease may play an important role for inducing [3H]TdR release from the target cells. PMID- 8370077 TI - B cell differentiation. II. Isotype potential of a single B cell. AB - Clonal, functionally responsive B cells are important tools for analyzing B cell activation and differentiation. Previously, we developed a method to immortalize murine B lymphoblast cells using an oncogene-carrying retroviral vector. The immortalized B cells express a cell surface phenotype similar to that of normal splenic B cells. These cells were shown to respond to B cell polyclonal mitogens and IL-4. More significantly, these cells could form conjugates with TH2 cells in the presence of a T cell superantigen. The T-B interaction promoted by the T cell superantigen resulted in B cell differentiation as demonstrated by IgM secretion and switching to IgG1 production. In this report, we analyze Ig isotype potential using two retrovirus-immortalized B cell clones. The clonality of both B cell clones was confirmed by Southern blot analysis using JH probes. It was found that anti-CD3-activated TH1 and TH2 cells promoted clonal B cells to differentiate into IgM-secreting cells. More significantly, activated TH1 cells promoted clonal B cells to switch to IgG2a production, whereas activated TH2 cells promoted clonal B cells to switch to IgG1 production. Thus, depending on which type of T helper cell a given B cell interacts with, a single B cell has the potential to switch to more than one Ig isotype. Addition of rIL-4 and anti-IFN-gamma to cultures containing TH1 and B cells resulted in IgG1 production (in addition to IgG2a production). Similarly, addition of IFN-gamma and anti-IL-4 to cultures containing TH2 and B cells resulted in IgG2a production (in addition to IgG1 production). Therefore, interaction of B cells with a given type of T helper cells could commit the B cells to a given Ig isotype. However, the presence of exogenous cytokines could divert B cells to switch to other Ig isotypes. PMID- 8370078 TI - Retinoids enhance IgA production by lipopolysaccharide-stimulated murine spleen cells. AB - The effect of all-trans retinoic acid (RA) and vitamin A on IgA production by LPS stimulated murine spleen cells was studied. Concentrations of immunoglobulins of six subclasses in the culture medium were determined. Only IgA level increased, RA dose dependently. In contrast, IgG1 level decreased and other subclasses (IgM, IgG2a, IgG2b, and IgG3) were not significantly affected by the treatment. IgA levels in LPS-stimulated spleen cells were usually between 10 and 100 ng/ml. When RA was added at the concentrations above 0.1 nM, the levels were increased dose dependently and peak response (8- to 20-fold) was observed from 0.1 to 1 microM. Enhancement of IgA secretion begins after 4 days culture and then increases linearly until Day 7. Vitamin A also showed IgA-enhancing activity, although its activity was about 1/170 of that of RA. TGF-beta activity in the culture medium was also determined, finding that RA rapidly stimulates secretion of biologically active TGF-beta, the elevation being evident after 1 day of culture. Specific neutralizing antibodies to TGF-beta 1 and TGF-beta 2 partially inhibited IgA enhancement caused by RA. These results suggest that retinoids at physiological concentrations may act as positive regulators for IgA production and the effect may be mediated, at least in part, via the induction of active TGF-beta. PMID- 8370079 TI - Suppression of local and systemic GVHR by supernatants from human choriocarcinoma cell lines. AB - Graft versus host reaction (GVHR) and host versus graft reactivity during pregnancy share at least some cellular pathways. Immunosuppression mediated by placental suppressor factors may actively contribute to the survival of the conceptus in the immunocompetent mother. We have previously reported that supernatants from human choriocarcinoma cell lines inhibit mitogen-activated and antigen-activated proliferation of lymphoid cells. From this perspective, we investigated the capacity of supernatants from human choriocarcinoma cell lines (HCS) to suppress in vivo graft versus host reactions in mice. HCS was tested for its ability to block both local as well as systemic GVHR induced by the injection of parental cells into F1 mice. HCS mediates profound suppression of acute and chronic GVHR. These results confirm that human choriocarcinoma cell lines secrete a potent immunosuppressive factor(s) which can efficiently modulate immune responses in vivo. PMID- 8370080 TI - Inhibitors of cytochrome P450 suppress tumor necrosis factor production. AB - We tested the effect of different inhibitors of cytochrome P450 on tumor necrosis factor (TNF) production. Metyrapone and SKF525A (100 and 50 mg/kg, ip, respectively) suppressed serum TNF induced by cotreatment with endotoxin (LPS), (2.5 micrograms/mouse). Inhibition was independent of endogenous corticosteroids since it was also observed in adrenalectomized mice. In vitro production of TNF by endotoxin-stimulated human monocytes was also inhibited by metyrapone and SKF525A. Since lipoxygenase (LO) inhibitors also block TNF production and metyrapone was reported to inhibit LO, we suggest that inhibition by metyrapone and SKF525A might be due to inhibition of either LO or a cytochrome P450 implicated in the oxidation of endogenous substrates involved in the inflammatory response. PMID- 8370081 TI - Double-negative (L3T4-, Lyt2-) thymocytes of autoimmune lpr/lpr mice are resistant to down-regulation of DNA synthesis by a thymic stromal cell product. AB - The murine autosomal recessive gene, lpr, induces a progressive lymphadenopathy and lupus-like autoimmune syndrome characterized by the accumulation of immature, dull Thy 1.2+, TCR+, L3T4-/Lyt 2- (double-negative, DN) T cells in peripheral lymphoid organs. Previous studies demonstrated that the thymic microenvironment is required for the generation of the abnormal, peripheral DN T cells, while a more recent report linked the lpr gene defect with a failure of thymocytes to express a functional form of the Fas antigen, which mediates apoptosis. Thus, the lpr gene defect apparently prevents lpr thymocytes from responding to the ordered sequence of differentiation and proliferation signals involved in normal thymocyte maturation and selection. We compared the responses of thymocytes from C57BL/6 +/+ (normal) and congenic C57BL/6 lpr/lpr (lpr) mice to a thymic stromal cell product which down-regulates DNA synthesis in vitro. The results indicate that (a) thymic stromal cells from lpr mice produce a factor that can down regulate DNA synthesis as efficiently as that from normal mice, even at an age when massive lymphadenopathy is present, (b) mitogen-stimulated thymocytes of normal, but not lpr, mice are sensitive to the inhibitory factor, (c) normal DN thymocytes are the cellular target of the inhibitory factor, which acts at some postmembrane receptor-ligand binding event during mitogen-stimulated proliferation, and (d) IL-4-dependent DN thymocyte proliferation seems to be the main target of the inhibitory factor. PMID- 8370082 TI - Both human and mouse cells expressing H-2Kb and ovalbumin process the same peptide, SIINFEKL. AB - HeLa cells, derived from a human cervix carcinoma line, were transfected with a mouse MHC class I gene, H-2Kb, and chicken ovalbumin. H-2Kb-restricted cytotoxic mouse T cells specific for ovalbumin recognized the double-transfected human cells with similar efficiency as ovalbumin-transfected EL4 mouse thymoma cells (H 2b). The naturally processed ovalbumin T cell epitope was eluted from H-2Kb molecules from double-transfected HeLa cells and was biochemically compared to a synthetic peptide, SIINFEKL, known to be the natural Kb ligand of ovalbumin transfected H-2b mouse cells. The results indicate that the ovalbumin-derived Kb ligand of double-transfected HeLa cells is also SIINFEKL. Thus, both human cervix carcinoma cells and mouse thymoma cells expressing Kb and ovalbumin process the same octapeptide. Together with previous data, derived by comparing Kb ligands of unknown sequences from both human and mouse cells expressing Kb, it can be concluded that both mouse and human cells are capable of processing the same ligands for mouse MHC class I molecules. Hence, the general specificity of the peptide-generating mechanism for class I ligands is apparently conserved between evolutionary distant species. PMID- 8370083 TI - Immunotargeting of thyroglobulin on antigen presenting cells abrogates natural tolerance in the absence of adjuvant. AB - Mice usually develop strong IgG responses to self-thyroglobulin (Tg) following immunization with mouse Tg (mTg) emulsified in complete Freund's adjuvant (CFA). Here we report that adjuvant-free challenge of mice with small doses of mTg conjugated onto a monoclonal antibody (MAb) specific for class II MHC determinants (anti-I-Ak) induces an mTg-specific IgG response in CBA (H-2k) but not in B6 (H-2b) mice. This is not a result of nonspecific uptake of immunoconjugate or chemical modification of mTg because mTg conjugated in a similar manner to a control MAb (specific for influenza nucleoprotein) of the same IgG subclass as the anti-I-Ak MAb did not elicit an autoimmune response. Despite the presence of mTg-specific IgG with titers equal to those observed after challenge with mTg in CFA, thyroid lesions were not detected in CBA mice that received mTg-(anti-I-Ak Mab) conjugate indicating a clear divergence in the requirements for autoantibody production and disease. The data suggest that small amounts of soluble autoantigen, conjugated onto MAbs specific for determinants expressed on antigen-presenting cells (APC), can effectively abrogate natural tolerance perhaps via a targeting mechanism that focuses autoantigen on APC. This approach may help elucidate the role of various APC subsets in autoimmunity and allow the study of initial events that trigger autoreactivity outside a CFA induced granuloma site. PMID- 8370084 TI - Antibodies for treating and preventing disease: the potential role of polymeric controlled release. AB - Following the identification of antibodies (Abs) as agents of immunity, it was hypothesized that individuals could be both (1) protected against disease by the transfer of unmodified Ab (passive immunization), and (2) cured of established disease by Ab armed with cytotoxic agents (immunotherapy). The development of monoclonal antibody (mAb) technology in 1975 reinvigorated these ideas. Although passive immunization has been practiced with great success for many years, successful tissue targeting by systemically delivered immunotoxins in humans has been documented in only a few cases. New modes of drug delivery, engineered for mAb-based products, may enable new applications of passive immunization and may provide improved tissue targeting for immunotherapy. By allowing sustained and tissue-localized delivery of mAb-conjugates, controlled-release polymers may play an important role in this effort. This article reviews the use of mAb in treating and preventing human disease, as well as the pharmacokinetics of Ab delivery. Two areas where controlled Ab release may yield new therapies are highlighted: sustained passive immunization of the mucus secretions and immunotherapy of brain tumors. PMID- 8370085 TI - Gastroretentive dosage forms. AB - This article begins with a review of gastric emptying, small intestine transit, and colonic transit of drug delivery systems with special attention paid to the different physiological processes involved in stomach emptying and to the cut-off size of nondigestible solids for passage through the gastroduodenal junction during the digestive phase. Then, the proposed means for prolonging the gastric residence time (GRT) of drug delivery systems are reviewed and analyzed with special emphasis on floating (F) dosage forms. The following means are discussed: the use of passage-delaying agents, large single-unit dosage forms, bioadhesive drug delivery systems, "heavy" pellets, and buoyant forms. In the section devoted to bioadhesive forms, the influence of the turnover time of the intestinal mucus gel layer on the performance of mucoadhesive preparations is pointed out to explain the poor results obtained in humans with such peroral products. The use of a specifically designed apparatus for measuring the total force acting vertically on an object immersed in a liquid is presented as a methodology for selecting optimized buoyant formations in vitro. Scintigraphic studies are described in nonfasting human volunteers either in upright or in supine posture, who concurrently were given one optimized F and one nonfloating (NF) hydrophilic matrix capsules of the same size, for three different sizes (small, medium, and large). In upright subjects, the F forms stayed continuously above the gastric contents irrespective of their size, whereas the NF ones sank rapidly after administration and never rose back to the surface thereafter. Consequently, the F forms show prolonged and more reproducible GRTs compared to the NF ones. The significance and extent of this prolongation are the most marked for the small size units (p < 0.001) but gradually lessen as the dosage form size increases (p < 0.05 for the medium size units), to become insignificant for the large size units (p > 0.05). Moreover, there is no significant difference between the mean GRTs of the small, medium, and large F units (p > 0.05). This indirectly confirms that the intragastric buoyancy of the F forms is the main process determining their prolonged GRT and protecting them from random gastric emptying related to antral peristaltism. Thus, their GRT depends mainly on the occurrence of the end point of digestion. To the contrary, the lasting retention of the NF forms in the stomach is only size dependent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8370087 TI - Treatment of Jehovah's Witnesses. PMID- 8370086 TI - Treating epilepsy--when, with what and by whom? PMID- 8370088 TI - National drug quality assurance system. PMID- 8370089 TI - Minimally invasive therapy. PMID- 8370090 TI - Changing trends in maternity care in Sri Lanka. PMID- 8370091 TI - Fungal skin infections in a paediatric dermatology clinic. AB - A diagnosis of fungal infection was established in 8.6% of patients who attended the dermatology clinic at the Lady Ridgeway Hospital, Colombo over a one year period. Only 4.3% were confirmed in the laboratory. The agreement between clinical and laboratory diagnosis was 96.6% for patients with typical clinical features, but only 26.4% for patients who did not have the classical appearance. Both direct microscopy and culture are required to determine the causative agent, although the majority (92%) of patients could be diagnosed on microscopy alone. Microsporum gypseum was the commonest fungus isolated from children. PMID- 8370092 TI - Effect of treatment on maximal expiratory flow rates in tropical eosinophilia. AB - Maximal expiratory flow rates such as peak expiratory flow rate (PEFR), rates at 25%, 50% and 75% of vital capacity (VE max 25%, VE max 50%, VE max 75%) and forced expiratory flow during the middle half of forced vital capacity (FEF 25 75%) were recorded in 23 patients with tropical eosinophilia (TE) before and after treatment. The mean values of all flow rates were significantly lower (P < 0.001) in untreated TE patients compared to predicted values. After three weeks' treatment with diethylcarbamazine, although there was a significant rise in the mean values of all expiratory flow rates (P < 0.05) except VE max 75% (P > 0.2), all flow rates continued to be significantly lower (P < 0.01) at one month than predicted values. PMID- 8370093 TI - Is drainage necessary after cholecystectomy? AB - There is controversy on the use of drains after cholecystectomy. This study was undertaken to test the claim that routine drainage after cholecystectomy was unnecessary. Results from 62 patients in whom cholecystectomy was performed without additional procedures on the biliary tract, demonstrated that there were no complications attributable to the absence of a drain. It is concluded that avoiding drainage does not interfere with a smooth outcome after cholecystectomy. On the contrary, it has distinct advantages. PMID- 8370095 TI - Aplastic anaemia complicating hepatitis A virus infection. AB - We report three patients with aplastic anaemia complicating hepatitis A virus infection. The pathogenesis and management of this rare complication which usually carries a poor prognosis, are briefly discussed. PMID- 8370094 TI - Management of missle injuries in a combat zone in Sri Lanka. AB - This series comprises 527 missile victims of armed combat managed at Base Hospital, Polonnaruwa (BHP) during a five year period commencing January 1984. The injuries were multiple and involved many regions of the body. The results are compared with recent reports from other countries with similar conflicts. The inadequacy of first aid and the lack of organised transport for the victims are emphasised with suggestions to improve the care of such patients. PMID- 8370096 TI - Acute pulmonary embolism in a patient with nephrotic syndrome. AB - Pulmonary embolism is a rare complication of nephrotic syndrome. We report the case history of a 30 year old man who presented with nephrotic syndrome and became acutely dyspnoeic with cyanosis and peripheral circulatory failure while on treatment. The clinical and ECG findings were strongly suggestive of acute pulmonary embolism. PMID- 8370097 TI - Dermoid cyst of the caecum. AB - Dermoid cysts of the caecum are rare and only four cases have been reported in the literature. They are sequestration cysts and are lined by squamous epithelium with skin appendages. Aetiologically these cysts may represent squamous metaplasia of enterogenous cysts or sequestration cysts due to epidermal inclusion at the time of closure of the neural groove. PMID- 8370098 TI - Sensible drinking? Why not a sensible smoking goal too? PMID- 8370099 TI - Eliminating leprosy from Sri Lanka--the launch of a social marketing campaign. PMID- 8370100 TI - Gait apraxia and headache. PMID- 8370101 TI - Effect of phosphatidylcholine and cholesterol on pH-sensitive liposomes. AB - We previously reported that liposomes composed of phosphatidylethanolamine (PE) and fatty acid exhibited pH-dependent leakage, aggregation and fusion (N. Hazemoto, M. Harada, N. Komatubara, M. Haga and Y. Kato, Chem. Pharm. Bull., 38, 748 (1990)). In this study, we have examined the effects of phosphatidylcholine (PC) and cholesterol (Chol) on the pH-sensitivity of liposomes. Contents-leakage from liposomes was always accompanied by a change in light-scattering, suggesting that aggregation or fusion of liposomes causes the leakage. The pH-sensitivity was observed only when liposomes contained less than 32 mol% of PC. The leakage vs. pH curves shifted to the more acidic regions as the PC content of the liposomes increased, but the maximum leakage (%) did not change. The effect of cholesterol on the pH-sensitivity depended on the PC/PE ratio of the liposomes. Addition of cholesterol to PC/PE/oleic acid (OA) liposomes system induced two effects, that is, aggregation of liposomes via the reduction in PC content and the stabilization of the liposomal membrane. It was shown that pH-sensitivity can be controlled by addition of the appropriate amount of PC and/or Chol to liposomal lipids. PMID- 8370102 TI - Investigation of the dimethylsulfoxide-trifluoroacetic acid oxidation system for the synthesis of cystine-containing peptides. AB - Disulfide bonds of peptides were effectively established between S-protected cysteine residues as well as free cysteine residues by the action of dimethylsulfoxide in trifluoroacetic acid. Oxytocin and alpha-human calcitonin gene-related peptide were synthesized using this oxidation system. The feasibility of this method for the formation of two disulfide bridges of apamin was also examined. PMID- 8370103 TI - Optically active antifungal azoles. I. Synthesis and antifungal activity of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-b utanol and its stereoisomers. AB - (2R,3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butano l [(2R,3R)-7] and its stereoisomers [(2S,3R)-, (2S,3S)- and (2R,3S)-7] were prepared from the optically active oxiranes 6 by a newly developed ring-opening reaction and evaluated for antifungal activity. The thiol (2R,3R)-7 showed extremely potent antifungal activity in vitro and in vivo. The optically active oxirane (2R,3S)-6, a useful intermediate for the synthesis of sulfur-containing antifungal azoles 5, was synthesized from methyl (R)-lactate [(R)-8] via eight steps in a stereocontrolled manner. The key step in the synthesis is the Grignard reaction of an amide derivative [(R)-12a] of (R)-lactic acid with 2,4 difluorophenyl-magnesium bromide (13). PMID- 8370105 TI - Synthesis and antihypertensive activities of new 1,4-dihydropyridine derivatives containing nitrooxyalkylester moieties at the 3- and 5-positions. AB - We have synthesized new 1,4-dihydropyridine derivatives having nitrooxyalkylester moieties at the 3- and 5-positions in order to develop potent and long-lasting vasodilators. The antihypertensive activities of these compounds were compared with that of nifedipine. One of them, 2-nitrooxypropyl 3-nitrooxypropyl 2,6 dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5- pyridinedicarboxylate (CD-349) was selected for further development. The structure-activity relationship is discussed. PMID- 8370104 TI - Optically active antifungal azoles. II. Synthesis and antifungal activity of polysulfide derivatives of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H- 1,2,4 triazol-1-yl)-2-butanol. AB - In an effort to find potent antifungal agents, a variety of optically active triazole derivatives with a polysulfide structure, 3, 4 and 5, were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The symmetrical polysulfides 3 (m = 2-4) were obtained by an oxidative coupling reaction of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl ) 2-butanol (1) or by the treatment of its thiocarbonate derivative 8 with potassium tert-butoxide. The unsymmetrical disulfides 5 were synthesized by the reaction of the thiol 1 with Bunte salts 11 or the thiosulfinate 12 or by the reaction of the thiocarbonate 8 with various thiols 13. All of these polysulfides showed potent antifungal activity against candidosis in mice. PMID- 8370106 TI - Structure-activity study of antihypertensive 1,4-dihydropyridine derivatives having nitrooxyalkyl moieties at the 3 and 5 positions. AB - 1,4-Dihydropyridine derivatives having two nitrooxyalkyl moieties as esters at the 3 and 5 positions possess antihypertensive activity. To understand how substituents affect the biological activity, the quantitative structure-activity relationship (QSAR) of 27 compounds was analyzed using the Fuzzy adaptive least squares (FALS 91) method. The QSAR models suggested that the hydrophobicity and electronic effect at the 4 position of the 1,4-dihydropyridine along with the special structures of the nitrooxyalkylester components are important for antihypertensive activity. PMID- 8370107 TI - Synthesis and pharmacological activities of novel cyclic disulfide and cyclic sulfide derivatives as hepatoprotective agents. AB - In order to search for anti-hepatitis drugs, we synthesized a series of eight- and nine-membered cyclic disulfides (1) and six- and seven-membered cyclic sulfides (2) and evaluated them for ability to reduce mortality in the model of acute hepatic failure induced by Propionibacterium acnes-lipopolysaccharide in mice. Compounds 1 were synthesized by oxidative cyclization of the corresponding dithiol derivatives (3) with diethyl bromomalonate or iodine. Compounds 2 were prepared from the methyl esters of 1 by desulfurization with tris(diethylamino)phosphine followed by deprotection. Compounds 1 were generally found to be more active than compounds 2. Compound 1b (SA3443) was found to exhibit potent protective activity. The synthesis and structure-activity relationships are discussed. PMID- 8370108 TI - Development of active center-directed plasmin and plasma kallikrein inhibitors and studies on the structure-inhibitory activity relationship. AB - The molecule of trans-4-aminomethylcyclohexanecarbonylphenylalanine 4 carboxymethylanilide (8), which is a potent and selective inhibitor of plasma kallikrein, can be divided into three parts (P1, P1' and P2'), each of which contains one of the rings. In order to study the role of each part in the manifestation of potent and selective inhibitory activity and the relationship between the structure and inhibitory activities toward plasmin, plasma kallikrein, urokinase and thrombin, each part was substituted with various other moieties to give many kinds of analogs and their inhibitory activities against the above enzymes were examined. Among them, trans-4 aminomethylcyclohexanecarbonyl-O-2-bromobenzyloxycarbon yltyrosine 4 acetylanilide (12) inhibited plasmin and plasma kallikrein with IC50 values of 2.3 x 10(-7) M and 3.7 x 10(-7) M, and K(i) values of 1.2 x 10(-7) M and 1.3 x 10(-7) M, respectively. PMID- 8370109 TI - 1,4:3,6-Dianhydrohexitol nitrate derivatives. I. Synthesis and antianginal activity of alkylpiperazine derivatives. AB - A series of 5-deoxy-5-(4-substituted piperazin-1-yl)-1,4: 3,6-dianhydro-L-iditol 2-nitrates was prepared and evaluated for oral anti-ischemic activities. Inhibition of lysine-vasopressin-induced T-wave elevation in the electrocardiogram (ECG) of rats (angina pectoris model) served as a primary assay. Optimum activity was observed for the compounds with the aryl-heteroatom (O,S, or N)-propyl group. Among them, the phenylthiopropyl-substituted compound 13 exhibited the most potent activity. Furthermore, intraduodenal administration (i.d.) of 13 tended to decrease left ventricular end-diastolic pressure (LVEDP) in a propranolol-induced heart failure model (dogs) and showed a potent protective effect against reperfusion arrhythmia in rats. Thus, 13 (KF 14124) is under further study as an orally active nitrate. PMID- 8370110 TI - 1,4:3,6-Dianhydrohexitol nitrate derivatives. II. Synthesis and antianginal activity of aryl- or arylcarbonylpiperazine derivatives. AB - A series of 5-(4-aryl- or 4-arylcarbonylpiperazin-1-yl)-5-deoxy-1,4: 3,6 dianhydro-L-iditol 2-nitrates was prepared in order to obtain orally active, nitrate-type vasodilators with reduced side effects. Our drug design was based on a small reduction in the lipophilicity compared to that of 5-deoxy-5-[4-(3 phenylthiopropyl)piperazin-1-yl]-1,4: 3,6-dianhydro-L-iditol 2-nitrate (1, KF14124). Compounds 4h (aryl = benzimidazol-2-yl), 4i (arylcarbonyl = nicotinoyl), and 4w (arylcarbonyl = 3-furoyl) showed potent anti-ischemic activity in a lysine-vasopressin-induced angina pectoris model (rats), and their structure-activity relationships are discussed. Compound 4i exhibited potent vasodilation of the coronary artery in anesthetized dogs and also exhibited potent preload reduction in a heart failure model (dogs) as compared with isosorbide dinitrate (2), nicorandil (3), and KF14124 (1). Furthermore, 4i showed much weaker acute lethal toxicity and less central nervous system depression than 1 in mice. Thus, 4i (KW-3196) is under development as a vasodilator and a drug for treating angina pectoris. PMID- 8370111 TI - A widely applicable electrode sensitive to basic drugs based on poly(vinyl chloride) membrane plasticized with tricresyl phosphate. AB - A plastic membrane ion-selective electrode applicable to many basic drugs has been developed. The electrode developed was constructed with tricresyl phosphate and a poly(vinyl chloride) matrix on a polytetrafluoroethylene film. The electrode showed a near-Nernstian response to chlorpromazine, trihexyphenidyl, imipramine, dibucaine, papaverine, propranolol, tetracaine, trazodone, quinidine and cinnarizine. The determination of 50 to 3000 micrograms/ml of trazodone hydrochloride in a pH 4.0 acetate buffer solution showed an average recovery of 99.4% (mean standard deviation 0.7%) by direct potentiometry. Inorganic cations and pharmaceutical excipients did not interfere with the determination. Trazodone hydrochloride and trihexyphenidyl hydrochloride in tablets were determined, and the results compared favorably with those obtained by conventional methods. PMID- 8370112 TI - Senegoses A--E, oligosaccharide multi-esters from Polygala senega var. latifolia Torr. et Gray. AB - From the roots of Polygala senega var. latifolia Torr. et Gray five new oligosaccharides, called senegoses A--E, were isolated and their structures were elucidated by spectroscopic and chemical means. These oligosaccharides were esterified with acetic, benzoic, trans-ferulic and cis-ferulic acids. PMID- 8370113 TI - Design and preparation of ethyl cellulose microcapsules of gadopentetate dimeglumine for neutron-capture therapy using the Wurster process. AB - Microcapsules of hygroscopic, highly water-soluble gadopentetate dimeglumine (Gd DTPA-DM) for use in preliminary in vivo experiments for neutron-capture therapy were designed. They were prepared with such properties as a particle size small enough to be suspended and injected through a syringe, a negligible release of Gd DTPA-DM, and a high drug content by means of the Wurster process, a spray coating method using a spouted bed with a draft tube. They were composed of lactose cores of 53-63 microm, an undercoat of ethyl cellulose (EC) and polyvinylpyrrolidone (PVP), a drug-layer of Gd-DTPA-DM, EC and PVP, a waterproof coat and a release sustaining overcoat of EC and cholesterol (1:1), and a surface treated with hydrogenated egg lecithin. By curing at 110 degrees C for 30 min after mixing with 20% pulverized mannitol powder, the 20% overcoating suppressed the release of Gd-DTPA-DM from 75-106 microm microcapsules to less than 10% for the first 20 min, which was the period required to prepare a suspension, inject it and irradiate the neutron. The microcapsules could be used to confirm that the intracellular presence of Gd is not critical in gadolinium neutron-capture therapy. PMID- 8370114 TI - Preparation and pharmacological evaluation of N3-substituted thymidine derivatives as central depressants. AB - Central depressant effects in mice of N3-substituted thymidines (Td) (1) were examined by intracerebroventricular (i.c.v.) injection. Nine derivatives including the methyl, ethyl, propyl, allyl, benzyl, xylyl and alpha-phenylethyl derivatives at the N3-position of 1 were synthesized and their pharmacological effects were evaluated by using hypnotic activity, pentobarbital-induced sleep prolongation and locomotor activity as indices for central depressant effects. At a dose of 2.0 mumol/mouse, the values of mean sleeping time induced by N3 benzylthymidine (6), N3-o-xylylthymidine (7), N3-m-xylylthymidine (8), N3-p xylylthymidine (9) and N3-alpha-phenylethylthymidine (10) were 61, 30, 48, 45 and 23 min, respectively. These derivatives (2.0 mumol/mouse) prolonged pentobarbital induced (40 mg/kg, i.p.) sleeping time. None of the alkyl (2-4) or allyl (5) derivatives exerted hypnotic activity, although the derivatives tested (2-10) significantly prolonged the pentobarbital-induced sleeping time. Compound 1 and its xylyl derivatives tested (0.25 mumol/mouse, i.c.v.) decreased locomotor activity. These results indicate that thymidine derivatives have central depressant activity, and the benzyl derivatives but not alkyl derivatives possess a hypnotic activity. PMID- 8370115 TI - Cytotoxic sesquiterpenes from Nardostachys chinensis. AB - Five cytostatic sesquiterpenes, desoxo-narchinol-A (1), nardosinone (2), debilon (3), nardosinonediol (4) and kanshone A (5), were isolated from the roots and rhizomes of Nardostachys chinensis (Valerianaceae). The steric structure of 1 was determined by nuclear Overhauser effects (NOEs) and the exciton chirality method. All five showed cytotoxic activity against P-388 cells and the structure-activity relationship of 1 was also discussed. PMID- 8370116 TI - Isolation of camelliaside C from "tea seed cake" and inhibitory effects of its derivatives on arachidonate 5-lipoxygenase. AB - A new flavonol glycoside, camelliaside C, was isolated from "tea seed cake" prepared from the defatted seeds of Camellia sinensis O. Kuntze. The structure was determined as kaempferol 3-O-beta-D-galactopyranosyl-(1-->2)-beta-D glucopyranoside by spectroscopic methods (FAB-MS, UV, IR, 1H- and 13C-NMR) and the enzymatic transformation of camelliaside C to astragalin. Camelliaside C showed an inhibitory effect on the arachidonate 5-lipoxygenase of RBL-1 cells (IC50:1.4 x 10(-4)M) as did camelliaside A and B isolated from the same product. PMID- 8370117 TI - Sulfoorientalols a, b, c, and d, four new biologically active sesquiterpenes from Alismatis rhizoma. AB - Four new sesquiterpenes, sulfoorientalols a, b, c, and d, having a sulfonic acid function were isolated from Chinese Alismatis Rhizoma. Their structures were determined on the basis of chemical and physicochemical evidence. Sulfoorientalols inhibited the contraction of isolated bladder smooth muscle induced by carbachol. PMID- 8370118 TI - Ca2+ and segment length dependence of isometric force kinetics in intact ferret cardiac muscle. AB - The influence of Ca2+ and sarcomere length on myocardial crossbridge kinetics was studied in ferret papillary muscle by measuring the rate of force redevelopment following a rapid length step that dropped the force to zero. Tetanic stimulation with 5 mumol/L ryanodine was used to obtain a steady-state contraction, and segment length was measured and controlled using a sense-coil technique that measures changes in the cross-sectional area of the central region of the muscle. The rate constant for the recovery of force (ktr) following a rapid length release was obtained by fitting the data with a single exponential function. Contrary to results from skinned skeletal fibers in which ktr increases almost 10 fold from low to maximal activation levels, ktr was found not to increase at higher activation levels in this study. Similarly, although force increased with segment length under all conditions, ktr never increased with length. Data presented here are consistent with a model of myocardial Ca2+ activation in which Ca2+ modulates the number of crossbridges interacting with the thin filament and are inconsistent with a model in which Ca2+ modulates the kinetics of transitions to force producing states within the actomyosin cycle. Differences in the activation dependence of the force redevelopment rate between cardiac and skeletal muscle suggest that there are fundamental differences in the mechanism of Ca2+ activation between these two muscle types. PMID- 8370119 TI - Molecular structure and transcriptional function of the rat vascular AT1a angiotensin receptor gene. AB - Rat vascular angiotensin receptors (AT1a receptors) are encoded by two mRNA transcripts sharing an identical receptor coding sequence but differing in their 5' and 3' untranslated sequences. We screened male Sprague-Dawley rat genomic libraries to clone the vascular AT1a receptor gene. Two sets of overlapping clones were isolated that encode over 90 kb of genomic sequence around the AT1a receptor gene. Four overlapping clones were identified from the 5' flanking portion of the gene. These contain the promoter region and two exons, 141 bp and 89 bp in size, respectively, encoding the alternatively spliced 5' untranslated mRNA sequence. Six additional clones overlap each other but do not overlap the set of clones from the 5' flanking region of the gene. These contain a single 1977-bp exon that encodes 900 bp of the 5' and 3' untranslated sequences in addition to a 1077-bp open reading frame identical to that found in vascular smooth muscle cell AT1a receptor cDNAs. Primer extension and RNase protection studies indicate that the transcription start site for this gene begins 9 bp upstream from the most 5' sequence found within the AT1a receptor cDNAs. Our mapping studies of the cloned gene, which so far includes an uncloned gap within the second intron, indicate that the transcription start site is no less than 67 kb upstream from the receptor coding exon. Promoter-reporter assays were performed by transfection of vascular smooth muscle cells with deletions of a 3.2 kb promoter region fused to a luciferase cDNA reporter plasmid. Relatively strong basal transcriptional activity is observed from the 5'-most 2 kb of the promoter and diminishes markedly with deletions within 1 kb of the early promoter region, suggesting strong promoter elements in the more upstream regions of the gene. Deletion of a 53-bp early promoter region containing the transcription start site and a putative TATA box completely abolishes the ability of upstream elements to drive transcription of the luciferase cDNA. These results indicate that we have isolated the AT1a receptor gene and its functional promoter. PMID- 8370121 TI - Heart-specific targeting of firefly luciferase by the myosin light chain-2 promoter and developmental regulation in transgenic mice. AB - Based on hybridization studies indicating constitutive expression levels of the endogenous myosin light chain-2 (MLC-2) gene in embryonic, fetal, and adult myocardium, a model system for selective targeting of genes to the heart of transgenic mice has been developed. A 2.1-kb DNA fragment of the 5' flanking region of the rat cardiac MLC-2 gene was fused to the firefly luciferase reporter gene and introduced into fertilized mouse oocytes. In four independent transgenic mouse lines, the expression of the MLC-2-luciferase fusion gene was found exclusively in heart muscle. In contrast to the endogenous MLC-2 gene, no luciferase activity was detectable in slow-twitch skeletal muscle or any other tissue of transgenic mice. This result suggests that the 2.1-kb DNA fragment of the 5' flanking region of the cardiac MLC-2 gene contains the regulatory elements required for selective gene expression in cardiac myocytes in vivo. In contrast to the endogenous steady-state MLC-2 expression during development, transgenic luciferase activity was 10-fold higher during embryogenesis, when formation of the ventricular loop and septum takes place. The enhanced luciferase activity in early heart development may suggest a growth-dependent control mechanism, involving either transcriptional or posttranscriptional regulation. In conclusion, this model system with the 2.1-kb ventricle-specific MLC-2 promoter sequence should facilitate the overexpression of gene products in the developing and mature heart muscle and further elucidate molecular mechanisms of myocardial diseases such as cardiomyopathies. PMID- 8370120 TI - Characterization of promoter elements of the rabbit cardiac sarcoplasmic reticulum Ca(2+)-ATPase gene required for expression in cardiac muscle cells. AB - The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) plays a critical role in the contractile performance of cardiac and slow-twitch skeletal muscle by restoring cytosolic calcium to low resting levels during the contractile cycle. We have previously shown that SERCA2 expression in the heart is altered by a number of pathophysiological stimuli. In an effort to define molecular mechanisms regulating expression of the SERCA2 gene in cardiac muscle cells, deletions of a 1460-bp promoter fragment were generated and inserted into a luciferase reporter plasmid. Promoter constructs were transiently transfected into embryonic cardiocytes and skeletal muscle cell lines Sol 8 and C2C12 in vitro and injected into adult myocardium in vivo. Results demonstrate that sequences from the transcription start site to -284 are both necessary and sufficient for high-level transcription of the reporter gene in differentiating muscle cells and in fetal cardiocytes in culture. We further demonstrate that this promoter fragment is highly active in vivo when injected into rat hearts, suggesting that the same regulatory elements are functional in vivo as well as in vitro. The region of the gene from -284 to -658 exerts a modest positive effect in cardiocytes and Sol 8 myotubes but exerts a negative effect in C2C12 fast skeletal muscle cells. This initial analysis of transcriptional regulation of the SERCA2 gene will serve as a foundation for the study of alterations of expression of the gene in pathological conditions. PMID- 8370122 TI - Malondialdehyde and glutathione production in isolated perfused human and rat hearts. AB - A number of studies show the relation between oxygen-derived free radicals and cardiac ischemia/reperfusion injury. However, little is known about oxidative stress in the human heart, which can be measured by oxidized glutathione (GSSG) and malondialdehyde (MDA) formation. Furthermore, data on MDA production by rat hearts are controversial, possibly because of the use of the aspecific thiobarbituric acid assay. Therefore, GSSG and MDA were measured, with colorimetric and high-performance liquid chromatographic assays, respectively, in buffer-perfused explanted human hearts and normal rat hearts made temporarily ischemic. Human hearts received cardioplegia; rat hearts were studied in a control and an ischemic group with or without cardioplegia. Baseline GSSG release was < 0.01 nmol.min-1.g wet wt-1 in both species. During reperfusion, GSSG release from human hearts and from ischemic and cardioplegic/ischemic rat hearts peaked at 0.24 +/- 0.12, 1.1 +/- 0.4, and 0.19 +/- 0.04 nmol.min-1.g-1, respectively. MDA was undetectable (< 0.02 nmol.min-1.g-1) in the effluent of both species and in human hearts (< 4 nmol/g protein). Rat heart reduced glutathione levels decreased 32% as a consequence of cardioplegia and ischemia. Cardioplegia induced a 41% (P = .08) decrease in rat heart MDA content, whereas cumene hydroperoxide increased it 3.6 times (P < .01). Thus, after ischemia human and rat hearts release GSSG, indicating that oxidative stress has occurred. Apparently, lipid peroxidation takes place in normal rat hearts, decreases after cardioplegia, but does not increase after ischemia/reperfusion. Human hearts lack MDA under normoxic and ischemic conditions. This novel finding seems to reflect a low MDA-forming potential in both situations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370123 TI - Selective induction of an embryonic fibronectin isoform in the rat aorta in vitro. AB - The temporal changes in the expression of fibronectin and other extracellular matrix genes were studied in rat aortic rings incubated in vitro in a serum-free medium. Changes in all forms of fibronectin mRNA increased progressively during the 24-hour incubation period, although an increase in the alternatively spliced form of fibronectin designated EIIIA was most pronounced. Both collagen and elastin mRNA levels decreased markedly during the 24-hour interval, as did alpha actin mRNA. The increase in the relative amount of the EIIIA isoform after a 24 hour incubation was also shown using ribonuclease protection assays. In situ hybridization showed the distribution of the induced fibronectin mRNA to be within all cell types, including endothelial cells, medial smooth muscle cells, and adventitial fibroblasts. Localization in the media was not uniform and was clearly identified mainly in clusters of cells distributed throughout the media. The early induction of fibronectin mRNA was inhibited by genistein, implicating tyrosine kinase activation as a causative factor in fibronectin expression. The in vitro changes reported may reflect a phenotypic change in vascular cell types that is both similar to and different from the changes reported in vivo under conditions in which vascular injury and repair occur. PMID- 8370124 TI - Dynamic interaction between cardiac myosin isoforms modifies velocity of actomyosin sliding in vitro. AB - To study the functional significance of cardiac isomyosin heterogeneity, active sliding of actin-myosin was studied using two different types of in vitro motility assay systems: (1) a sliding actin filament assay, in which fluorescently labeled actin filaments were made to slide on a myosin layer attached to a glass coverslip, and (2) a myosin-coated bead assay, in which myosin-coated latex beads were made to slide on actin cables of an alga. Two different isomyosins were obtained from 3-week-old (V1) and hypothyroid (V3) rat hearts and were mixed to form solutions with various mixing ratios [V1/(V1 + V3)]. For these myosin mixtures, both ATPase activity and sliding velocity of actin-myosin were determined. As the relative content of V1 increased, both ATPase activity and velocity increased. However, in contrast to the linear relation between the mixing ratio and ATPase activity, the relation between the mixing ratio and sliding velocity was sigmoid, suggesting the existence of mechanical interaction between different isomyosins. To clarify the nature of this interaction, sliding velocity was measured for mixtures of V1 and p-N,N' phenylene-dimaleimide-treated V1 myosin (pPDM-M). A convex relation was observed between the relative content of pPDM-M and velocity. Because pPDM-M is known to form a noncycling and weakly bound crossbridge with actin, it is expected to exert a constant internal load on V1, in contrast to the actively cycling V3. In conclusion, in actomyosin sliding, different isomyosins mechanically interact when they coexist. The interaction may be a dynamic one that cannot be explained by a simple load effect. PMID- 8370125 TI - Spontaneous sarcomeric oscillations at intermediate activation levels in single isolated cardiac myofibrils. AB - Spontaneous oscillations observed in various heart muscle preparations are widely thought to be triggered by spontaneous release of Ca2+ from the sarcoplasmic reticulum (SR). Here, we report undamped propagated oscillations that occur in the absence of SR. In single cardiac myofibrils treated with Triton X-100 to remove SR and held isometrically, partial activation initiated periodic fluctuations of sarcomere length persisting up to 1 hour. Oscillation characteristics could be readily quantitated by virtue of the small size of the preparation. In an individual sarcomere, the oscillation cycle generally consisted of a slow shortening phase, followed by a phase of rapid lengthening. Oscillations usually propagated along the myofibril--frequently along the entire specimen--in a wavelike fashion (average velocity, 12.3 microns/s at 10 degrees C; Q10, approximately 1.3). The oscillation period was 2.30 and 1.72 seconds at 10 degrees and 20 degrees C, respectively, and was insensitive to stretch. The average oscillation amplitude, which was temperature independent, decreased with stretch from more than 20% of the mean sarcomere length at lengths below 2 microns to zero beyond a sarcomere length of 3 microns. Stiffening of the Z line by labeling with anti-alpha-actinin resulted in a dose-dependent decrease of oscillation amplitude, while the period was not affected. Tension oscillations could not be detected in single myofibrils but were frequently detectable in myofibril doublets, where the oscillation magnitude (approximately 1 microgram) was above the noise floor. Addition of 10 mumol/L ryanodine to the activating solution did not alter oscillation characteristics, as expected, since the oscillations are unrelated to SR calcium release. On the basis of our results, we consider a mechanism for the oscillations in which a length dependence of myofibrillar Ca2+ sensitivity and a dynamic Z-line structure are essential. PMID- 8370126 TI - Glibenclamide, a putative ATP-sensitive K+ channel blocker, inhibits coronary autoregulation in anesthetized dogs. AB - We tested the hypothesis that ATP-sensitive K+ channels are involved in the mechanism mediating coronary autoregulation in open-chest dogs. We perfused the left anterior descending coronary artery with arterial blood from an extracorporeal circuit and measured steady-state coronary blood flow (CBF) with stepwise changes in coronary perfusion pressure (CPP) between 50 and 150 mm Hg during an intracoronary infusion of vehicle or glibenclamide (a putative blocker of ATP-sensitive K+ channels). CBF was relatively stable over CPP between 50 and 110 mm Hg during vehicle infusion, indicating the presence of autoregulation at the CPP range. During glibenclamide infusion (10 micrograms.min-1 x kg-1), CBF progressively decreased with reduction in CPP below 110 mm Hg, whereas the CPP CBF relation at CPP above 110 mm Hg was not altered by glibenclamide. The autoregulation index [1-(delta F/F)/(delta P/P), where F indicates CBF and P indicates CPP] was greater than 0 over the CPP range between 50 and 100 mm Hg during vehicle infusion and was less than 0 during glibenclamide infusion. Glibenclamide did not alter systemic arterial pressure, heart rate, left ventricular pressure, and changes in regional myocardial oxygen consumption associated with changes in CPP. In the absence of glibenclamide, the CPP-CBF relation was reproducible in the repeated studies for time control. These results suggest that ATP-sensitive K+ channels play an important role in mediating coronary autoregulation at the lower range of CPP in the blood-perfused dog heart. PMID- 8370127 TI - The treatment of women with hirsutism. PMID- 8370128 TI - The impact of a pure anti-androgen (flutamide) on LH, FSH, androgens and clinical status in idiopathic hirsutism. AB - OBJECTIVES: We assessed in women the effects of androgen suppression on gonadotrophin secretion and the therapeutic efficacy of the pure anti-androgen flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide). DESIGN AND SUBJECTS: Ten women, aged 28-35 years, using an intrauterine device for contraception, were selected for this study. All women had idiopathic hirsutism with or without acne and seborrhoea. Flutamide was administered orally in a dose of 250 mg twice daily for 1 year. Basal body temperature was recorded and pelvic ultrasonography performed before and every 3 months during treatment. LH pulse frequency and amplitude (Cluster analysis) and basal and GnRH-stimulated plasma LH and FSH levels were determined on day 5 of the cycle prior to flutamide treatment, and after 6 and 12 months of therapy. Plasma total testosterone (T), non-SHBG bound T, androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), androstanediol glucuronide (3 alpha-diol G) and sex hormone binding globulin (SHBG) levels were measured before and every 3 months during therapy, on day 5 of the cycle. Plasma oestradiol and progesterone levels were determined on day 22 of the studied cycles. RESULTS: Disappearance of acne and seborrhoea occurred after 2 months with a marked improvement of hirsutism at 6 months. At 12 months, hirsutism had disappeared with a Ferriman and Gallwey score < 7. No adverse side effects, apart from transient diarrhoea in two patients, were reported with this flutamide dose. None of the patients had any disturbance of menstrual cycles which remained ovulatory. The pure anti-androgen flutamide induced no significant change in LH pulsatile profile, nor in LH and FSH responsiveness to GnRH. Plasma concentrations of steroids were not altered. Plasma SHBG and 3 alpha-diol G levels did not change during flutamide treatment. CONCLUSION: Flutamide, which interacts only with the androgen receptor, is effective for hirsutism, acne and seborrhoea, and does not disturb menstrual cyclicity or ovulation. It may represent a treatment of choice for essential hirsutism in women using safe contraceptive methods. PMID- 8370129 TI - Circadian variation in serum free and non-SHBG-bound testosterone in normal men: measurements, and simulation using a mass action model. AB - OBJECTIVE: We measured the changes in testosterone fractions in serum of normal men over a 24-hour period, and determined whether they could be simulated on the basis of current understanding of the interactions between steroids and binding proteins in the blood. DESIGN: Starting from between 0830 and 0930 h, blood samples were taken every 45 minutes for 25.5 hours. PATIENTS: Five healthy males aged 26-45 years. All participants worked on a hospital campus and while being sampled carried out their normal activities during waking hours. MEASUREMENTS: The concentrations of testosterone (RIA) and albumin, and the percentage non-sex hormone binding globulin-bound testosterone (ammonium sulphate precipitation) and percentage free testosterone (rate dialysis), were measured on each sample. Cortisol (RIA) and sex hormone-binding globulin (SHBG) (IRMA) concentrations were measured on every second sample, and that of corticosteroid-binding globulin on two samples from each series. RESULTS: In all participants the levels of free and non-SHBG-bound testosterone in early morning samples (near 0530 h) were significantly different from those taken before midnight (P < 0.0005). Significant circadian rhythms (P < 0.05) in the concentration of testosterone and in the level of the free fraction were detected in all participants, and in four of the five participants for the non-SHBG-bound fraction. The amplitude of the free testosterone rhythm (34 +/- 2% of basal) was greater than that for testosterone itself (24 +/- 3% of basal). The 24-hour rhythm of the non-SHBG bound fraction was similar to the total and free fractions except for the period 0330-0900 h when the level of this fraction declined by 15-45% over 1.5-3 hours. This decline was coincident with the initial rise in the concentration of cortisol. A decline of 10.5 +/- SEM 1.0% in the concentration of albumin, and 12.0 +/- 1.1% in that of SHBG occurred when the mean ambulant and supine levels were compared; analysis indicated significant circadian rhythms in the concentrations of these proteins. Simulation was used to investigate possible causes for the circadian rhythms in free and non-SHBG-bound testosterone. Simulation results matched the measured data well in qualitative terms, but quantitatively there were differences. CONCLUSIONS: Increasing saturation of the binding proteins following rises in testosterone production, and the small but significant changes in protein concentration, probably related to postural changes, were implicated as the major factors in the rhythm amplitude. However, the early morning decline in the non-SHBG-bound fraction was not explained by these factors. The rise in cortisol concentration at this time is a probable cause. Alternatively, simulation suggests that a substance appearing in the early morning and competing with testosterone for albumin binding sites may be responsible. PMID- 8370130 TI - Molecular heterogeneity of serum follicle-stimulating hormone in hypogonadal patients before and during androgen replacement therapy and in normal men. AB - OBJECTIVE: The present study was performed to characterize the molecular heterogeneity of serum FSH in normal males and to investigate the possible influence of testosterone on serum FSH in androgen-deficient men before and during testosterone administration. DESIGN AND PATIENTS: Serum samples were taken at 10-minute intervals between 0730 and 0830 h from nine healthy, eugonadal men and from eight men with primary hypogonadism (Klinefelter's syndrome). In the hypogonadal patients, sampling was performed before treatment (n = 8), 4-5 days after the first and the third injection of 250 mg testosterone enanthate given intramuscularly at three-weekly intervals (n = 6), as well as 3 months after the onset of therapy (n = 3). Sampling was repeated 7 days apart in two of the nine healthy volunteers. MEASUREMENTS: Aliquots from the individual serum samples were pooled and fractionated by chromatofocusing in the pH range 6-3. Immunoreactive FSH was measured by immunofluorometric assay (IFMA) in each fraction and the individual serum samples. In each serum pool, bioactive FSH was determined by in vitro bioassay (rat Sertoli cell aromatase bioassay), testosterone by RIA and LH by IFMA. RESULTS: After grouping the percentage of immunoreactive FSH recovered in the individual fractions into intervals of 0.5 pH units, significant differences between controls and patients were observed in the pH regions 4-4.5, 5.5-6 and 6-6.5. No statistically significant changes in the isoform distribution of FSH were detected during therapy in the Klinefelter patients. A high degree of variability, which did not follow a common pattern, was observed in the isoform distribution of FSH within the same individuals, both in the hypogonadal patients during treatment and in the two normal men whose blood samples were taken on two different occasions. CONCLUSIONS: Serum FSH is highly heterogeneous in normal and hypogonadal men. There is a spontaneous intra-individual variability in the relative abundance of the different FSH isoforms in serum that may most probably be related to metabolic deglycosylation of FSH. Minor but significant differences in the molecular heterogeneity of serum FSH could be demonstrated in Klinefelter patients compared to normal men. These differences are not modified by administration of testosterone enanthate at doses achieving normal androgenization, suggesting that factors different from testosterone may modulate FSH pleomorphism. PMID- 8370132 TI - Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone. AB - OBJECTIVE: There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release. DESIGN: The study consisted of four protocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 micrograms i.v. bolus). Study 2: GHRH (100 micrograms i.v. bolus) or placebo were administered at 0 minutes; oral melatonin or placebo were given at 60 minutes and were followed by a second GHRH stimulus (100 micrograms i.v. bolus) at 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions. Study 4: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3 micrograms i.v. bolus) of GHRH. SUBJECTS: Four groups of eight normal male subjects, ages 22-35 years, were randomly assigned to each protocol. MEASUREMENTS: Growth hormone was measured by RIA at 15-minute intervals. RESULTS: Oral melatonin administration had a weak stimulatory effect on GH basal levels. Prior melatonin administration approximately doubled the GH release induced by supramaximal (100 micrograms) or submaximal (3 micrograms) doses of GHRH. Melatonin administration restored the GH response to a second GHRH challenge, given 120 minutes after a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatonin. However, the simultaneous administration of melatonin and pyridostigmine was not followed by any further enhancement of GH release, either in the absence or in the presence of exogenous GHRH. CONCLUSIONS: Our data indicate that oral administration of melatonin to normal human males increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release, although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be established. PMID- 8370131 TI - Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women. AB - OBJECTIVE: The aim of the study was to evaluate the effects of exogenous melatonin on the spontaneous pulsatile release of PRL, TSH and LH in normal women. DESIGN: A double blind placebo-controlled protocol was designed to study seven subjects in the mid follicular phase of two non-consecutive cycles. Two mg of exogenous melatonin or placebo were given at 1600 and 2000 h, and blood samples were collected every 10 minutes from 1800 to 2400 h for hormone determination. RESULTS: Melatonin treatment caused a significant upward resetting of the pulsatile pattern of PRL in six out of seven subjects. Average maximal peak height was significantly increased (median 716 mIU/l (range 198-1433) on melatonin vs 324 mIU/l (212-688) on placebo, P < 0.001), nadir value (572 mIU/l (148-1084) vs 216 mIU/l (54-580), P < 0.001) and area under the peak (26352 mIU/l min (5904-93672) vs 12096 mIU/l min (2340-33552), P < 0.001), whereas peak number, amplitude and interpeak interval did not change significantly. TSH pulsatility was unaffected by melatonin administration in four out of six subjects. Distribution of LH patterns after melatonin was inhomogeneous: level of pulsatility was higher in two cases and reduced in three; group analysis did not therefore show significant variation of pulsatility parameters. CONCLUSIONS: Exogenous melatonin has a stimulatory effect on PRL release without affecting the temporal pattern of its pulsatile secretion in normal women. Melatonin has minor, if any, effect on TSH secretion whereas the effect on LH may depend on individual sensitivity. PMID- 8370133 TI - Urinary growth hormone excretion in the assessment of children with disorders of growth. AB - OBJECTIVE: We wished to evaluate the use of urinary GH measurements when compared to conventional GH provocation tests in the assessment of short children. DESIGN: Children presenting for the first time to a regional growth clinic were assessed clinically by one observer. Investigations comprising standard GH provocation tests and measurement of urinary GH were undertaken to exclude GH deficiency. PATIENTS: Fifty-eight children aged 5.8-16 years were enrolled. Ten were diagnosed on clinical assessment as GH deficient, 43 had delayed growth and/or familial short stature, and five had idiopathic short stature; the 48 children in the last two groups were defined as short normal. MEASUREMENTS: GH secretion was evaluated by two standard provocation tests and by the measurement of GH in five overnight urine collections. A normal peak GH concentration was defined as > 16 mU/l. The values for urinary GH excretion were compared to normal ranges (+/- 2 standard deviations from the mean), established in healthy schoolchildren of normal stature. RESULTS: All children considered GH deficient on clinical grounds had low peak GH concentrations on provocation tests, while 8/10 had low values of urinary GH excretion. All short normal children with normal peak GH concentrations (n = 36) on provocation tests and 11/12 children with low peak GH concentrations had urinary GH excretion within the normal range. There was therefore a significant difference in the classification of 'normal' GH secretion in the two tests. If the clinical diagnosis was used as the standard by which GH tests were judged, the predictive value of a positive urinary GH test in the diagnosis of GH deficiency was 89% compared with 45% for GH provocation tests. PMID- 8370134 TI - In-vitro response of erythroid progenitors from children with thalassaemia major to human growth hormone and insulin-like growth factor I. AB - OBJECTIVE: Most short-statured children with beta-thalassaemia major have markedly reduced levels of circulating insulin-like growth factor I (IGF-I). Both human growth hormone (hGH) and IGF-I enhance the in-vitro growth of erythroid progenitors, with hGH exerting its effects via paracrine production of IGF-I. The aim of this study was to characterize further the hGH-IGF-I axis abnormalities in thalassaemia major by evaluating the erythroid potentiating effects of both peptides in cultures of thalassaemic and control erythroid progenitors. DESIGN: Ten short-statured thalassaemic children and nine age-matched healthy donors were evaluated for the in-vitro response of their peripheral blood erythroid progenitors to stimulation with hGH and IGF-I. MEASUREMENTS: The frequency of erythroid progenitors in serum-free cultures of thalassaemic and control peripheral blood mononuclear cells was enumerated following 14 days of incubation in the presence of hGH or IGF-I. RESULTS: Biosynthetic hGH induced a similar dose dependent magnitude of colony enhancement in cultures of erythroid progenitors from thalassaemic children, as compared to controls. Significant enhancement of colony growth was detected at 42 mU/l hGH, with a maximal effect detected at 83 mU/l of this hormone (173 +/- 8 vs 153 +/- 9% of baseline erythroid progenitors in patients versus controls, respectively). Enhancement of both thalassaemic and control erythroid precursors by hGH was completely abrogated by monoclonal antibodies (alpha IR-3) directed against the IGF-I membrane receptor, thereby confirming the normal capacity of thalassaemic accessory cells to produce IGF-I in response to hGH. Biosynthetic IGF-I also enhanced the growth of thalassaemic and control erythroid precursors to 172 +/- 17 and 159 +/- 10% of baseline at 100 and 10 U/l, respectively. CONCLUSIONS: Our detection of a normal capacity of thalassaemic peripheral blood target cells to response to hGH and IGF-I suggests that these patients do not suffer from a specific defect in receptor and/or post receptor mechanism(s) involving the response of these cells to both peptides. The normal responsiveness of thalassaemic target cells to hGH and IGF-I suggests that both peptides may be useful in the treatment of growth retardation in thalassaemia. PMID- 8370135 TI - Protein intake during aggressive calorie restriction in obesity determines growth hormone response to growth hormone-releasing hormone after weight loss. AB - OBJECTIVE: We evaluated the influence of two types of calorie restriction, total fast or very low calorie diet, on GH responsiveness to GHRH in severely obese patients. DESIGN: Twenty patients with massive obesity underwent one of two types of calorie restriction, total fast (10 patients) or very low calorie diet (10 patients). MEASUREMENTS: Fasting GH, IGF-I, glucose, insulin and GH secretion after GHRH (100 ug i.v.) were assessed in all patients before and after diet therapy. RESULTS: Both types of diet produced similar weight reduction (total fast, 5.6 +/- 1.6 kg/m2 vs very low calorie diet, 5.6 +/- 1.5 kg/m2 mean +/- SD). A significant increase in the integrated GH secretion was observed after weight loss with very low calorie diet (17 +/- 9 vs 27 +/- 12 mU/l min; P < 0.05). However, no change was found in GH response after weight loss with total fast (13 +/- 5 vs 15 +/- 7 mU/l min). Glucose, insulin and IGF-I levels showed a significant decrease with weight reduction which was similar for both groups. CONCLUSION: These findings suggest that the type of dietary manipulation during calorie restriction in obese patients may influence the changes in GH response to GHRH after weight loss. PMID- 8370136 TI - Deficient inactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase in essential hypertension. AB - OBJECTIVE: 11 beta-Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from cortisol by converting cortisol to inactive cortisone. 11 beta Dehydrogenase deficiency, either congenital or after inhibition by liquorice and carbenoxolone, results in cortisol-dependent mineralocorticoid excess and hypertension. We tested the hypothesis that the same mechanism occurs in some patients with essential hypertension. DESIGN/PATIENTS: Twenty patients with essential hypertension were compared with 19 matched healthy controls. MEASUREMENTS: 11 beta-Hydroxysteroid dehydrogenase activity was assessed by the half-life of 11 alpha-3H-cortisol, and by the ratios of cortisol to cortisone in plasma and of their metabolites in urine. Renal mineralocorticoid receptor activation was assessed by plasma potassium, renin activity and aldosterone. RESULTS: Half-lives of 11 alpha-3H-cortisol were prolonged in a subgroup of hypertensives (mean +/- SE 53.2 +/- 3.6 min in hypertensives vs 42.3 +/- 2.3 in controls, P < 0.05; seven of the 20 hypertensives had half-lives exceeding 2 SD of controls). Ratios of cortisol to cortisone in plasma and of their metabolites in urine were not different. 11 alpha-3H-Cortisol half-lives correlated with blood pressure but not with indices of renal mineralocorticoid receptor activation. CONCLUSIONS: 11 beta-Dehydrogenase is defective in a proportion of patients with essential hypertension. The normal ratios of cortisol to cortisone in plasma and of their metabolites in urine, also seen after carbenoxolone administration, suggest that 11 beta-reductase conversion of cortisone to cortisol is also defective. Unlike other syndromes of 11 beta-dehydrogenase deficiency, the defect was not associated with mineralocorticoid excess. We suggest that it may cause hypertension by increasing exposure of vascular steroid receptors to cortisol. PMID- 8370137 TI - A case of antibody formation against octreotide visualized with 111In-octreotide scintigraphy. AB - A case of antibody formation in a patient with carcinoid syndrome is described. The patient was treated with octreotide in dosages up to 1.5 mg/day. Serum samples were analysed for the presence of octreotide antibodies before and after 20 months of octreotide treatment. In-vivo 111In-octreotide scintigraphy was performed before and during therapy, and after antibodies had developed. Before treatment, no serum antibodies against octreotide were detected. After 20 months of treatment, they were detectable up to a 1:115 serum dilution. The serum binding of 125I-Tyr3-octreotide was blocked by adding excess unlabelled Tyr3 octreotide, indicating the presence of specific octreotide antibodies. Before treatment, a normal distribution of radioactivity in the spleen and kidneys, irregular uptake in the liver due to metastases, and a hot spot in the lower abdomen were found during 111In-octreotide scintigraphy. After antibodies had developed, increased radioactivity over the heart and high background radioactivity in the abdomen with only faint visualization of the spleen, liver, and kidneys were found, indicating a prolonged presence of 111In-octreotide in the blood resulting from its being bound to antibodies. Increased radioactivity was also seen at the injection sites of the drug in the upper legs. In-vitro incubation of biopsy tissue from this site with 125I-Tyr3-octreotide revealed diffuse guanosine triphosphate (GTP) independent specific binding, indicating non G-protein linked binding of labelled octreotide. This report describes the characteristic abnormalities during in-vivo 111In-octreotide scintigraphy in a patient with octreotide antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370138 TI - Deoxycorticosterone, 11 beta-hydroxylase and the adrenal cortex. AB - We report a child in whom DOC excess secondary to congenital adrenal hyperplasia (CAH, 11 beta-hydroxylase deficiency) caused malignant hypertension. Clinical and metabolic control could be achieved only by replacement of both glucocorticoid and mineralocorticoid, thus confirming in clinical practice the hypothesis that DOC is produced from both the zonae fasciculata and glomerulosa of the adrenal cortex under the independent control of the ACTH and renin-angiotensin systems respectively. PMID- 8370139 TI - Thyrotoxicosis increases right to left shunt in congenital cyanotic heart disease. AB - We wish to report two cases of congenital cyanotic heart disease in whom coexisting thyrotoxicosis increased the right to left shunt. We review the literature on the cardiac and respiratory effects of thyroid hormone to try to explain this phenomenon. Two patients, one with Fallot's tetralogy (diagnosed at 68 years of age), the other with a ventricular septal defect, developed thyrotoxicosis which resulted in a dramatic but reversible deterioration in their cardiac condition. We conclude that thyrotoxicosis increases right to left shunt in congenital cyanotic heart disease. This effect is profound but reversible. We suggest that when an unexplained rapid deterioration occurs in patients with congenital cyanotic heart disease, thyrotoxicosis should be excluded. PMID- 8370140 TI - Factors influencing body weight regulation. AB - As obesity is a major health problem for both the adult and adolescent populations of the United States there is an increasing need to understand basic mechanisms that control the body weight of an individual. Body fat content in adults is determined by energy balance status which is influenced by both food intake and energy expenditure. Current evidence suggests a dominant role for control of intake although chronic exercise and genetic factors will influence body composition. The hypothalamus appears to be the brain area responsible for determining food selection and intake although it is not yet clear how central mechanisms modulate peripheral feeding and satiety responses. PMID- 8370141 TI - The gastrointestinal mucosal immune system. AB - The mucosal immune system, consisting of lymphoid tissues associated with the lacrimal, salivary, gastrointestinal, respiratory and urogenital tracts and lactating breasts, quantitatively contains the majority of the lymphoid tissue of the body. There are a number of important features of the gastrointestinal mucosal immune system: the mucosal immune system contains specialized structures, such as the Peyer's patches, where immune responses are thought to be initiated; there is a pattern of relatively specific recirculation of lymphoid cells to the mucosa, known as mucosal homing; subsets of lymphoid cells, particularly IgA B cells and memory T cells, predominate at mucosal surfaces; and the predominant mucosal immunoglobulin, secretory IgA, is particularly well adapted to host defense at mucosal surfaces. These elements of the gastrointestinal mucosal immune system function together to generate an immune response which on the one hand protects the host from harmful pathogens, but on the other hand is tolerant of the ubiquitous dietary antigens and normal microbial flora. PMID- 8370142 TI - Recent progress in senescence-associated gut mucosal immunity. AB - The immune response in gut-associated lymphoid tissues (GALT) is altered in the aging process. Senescence-induced quantitative decline and qualitative changes of GALT T and B cells and their subpopulations contribute largely to the impaired gut mucosal immune responses. Thus, not only direct cell-to-cell contact interactions, but also patterns of immuno-regulatory cytokine production and serum-soluble cytokine, such as interleukin-2 receptors are also altered, causing both cellular and humoral immune abnormalities in GALT. One of the characteristic features includes functional defects of suppressor T cells. As a consequence, relative hyperfunction of helper T cells ensures. The defective immune response of both function and control of aged GALT may help to explain the increased incidence of infection and neoplasia in the gastrointestinal tract with age. On the subcellular level, these aged T and B cells impair transmembranous signal transduction. Trials of immune interventions to reduce or reverse immunosenescence in GALT were made in animals. The results of adoptive transfer of in vitro educated helper T cells from aged GALT are encouraging. Further innovative immunologic interventions are indicated. PMID- 8370143 TI - Dissolution of gallstones. AB - Gallstones represent a major health problem in western society. For symptomatic gallstones, cholecystectomy is the gold standard. A considerable number of patients, however, cannot tolerate or are unwilling to undergo surgery and anaesthesia. For these patients, dissolution therapy, administered either systemically ('oral dissolution') or directly into the gallbladder ('contact dissolution'), might be preferable. In this review, the possibilities and limitations of dissolution therapy are discussed. It is concluded that dissolution is a good alternative in selected symptomatic patients and that it is useful as adjuvant therapy after lithotripsy (ESWL) of gall-bladder stones. PMID- 8370144 TI - Update on laboratory diagnosis and prognosis of acute pancreatitis. AB - In this review, the relative values of serum pancreatic enzyme assays and other laboratory tests for diagnosis and prognosis of acute pancreatitis have been evaluated. It is concluded that serum lipase measurement should be the preferred diagnostic method since it is as simple and accurate as amylase assay, all the while being more specific. As for prognosis, among the several biochemical tests now available, the most useful for clinical practice is serum C-reactive protein determination. PMID- 8370145 TI - Myotonic dystrophy: from linkage with secretor status to mutation detection. PMID- 8370146 TI - Direct molecular diagnosis of myotonic dystrophy. AB - Myotonic dystrophy (DM) arises from an unstable trinucleotide (CTGn) repeat sequence within the DM locus at 19q13.3. Twenty-three myotonic dystrophy families containing 205 persons with no symptoms, minimal manifestations, classic DM or congenital DM were investigated to validate the application of the pM10M6 probe to direct molecular diagnosis. Affected family members had been diagnosed clinically and the unaffected family members had been assigned carrier probabilities close to either zero or 100%, using closely linked flanking markers. Southern analysis identified all 89 DM gene carriers as having expansions of the unstable element. PstI detected all small expansions of the repeat sequence as easily seen discrete bands; but large expansions were usually seen as diffuse smears, sometimes difficult to distinguish from lane background. EcoRI concentrated these diffuse smears, associated with somatic instability, into discrete bands which were easy to detect; but it did not resolve the smaller expansions present in 9 (10%) of the DM carriers. It is essential that PstI and EcoRI gels are run in parallel to detect all DM gene carriers. The extent of expansion of CTG correlated with age of onset and disease severity. Biopsies of various fetal tissues from two terminated pregnancies confirmed the diagnosis obtained by CVS and revealed no heterogeneity between tissues at this developmental stage. Further expansion occurred during the culture of CVS cells, indicating that direct prenatal diagnosis needs to be carried out on CVS tissue rather than on cultured cells. The intergenerational change of the repeat sequence from DM parent to DM offspring showed a significant parental sex difference for those parents with large expansions. Contraction of the unstable element was observed in the three males carrying the largest expansions and could explain why congenital DM is exclusively of maternal origin. PMID- 8370147 TI - DNA analysis of distinct populations suggests multiple origins for the mutation causing Huntington disease. AB - Results of association studies can be significantly biased if the ancestry of the control population is not similar to that of the affected population. One approach to overcome such a bias is to use distinct populations where controls and affected individuals are likely to be of similar descent. We have examined homogeneous populations of French, Danish and Swedish ancestry for nonrandom allelic association between Huntington disease (HD) and several markers previously shown to be in association with HD. No evidence for nonrandom allelic association between HD and these markers was shown in these populations. The demonstration of association in a United Kingdom (UK) sample of similar size, and lack of significant differences in allele frequencies between the French, Danish, Swedish and UK populations suggested that the absence of association was not predominantly a consequence of allele frequencies or sample size. To investigate further the number of potential HD chromosomes, DNA haplotypes were constructed for the Danish, French, Swedish and UK populations. The minimum of two HD haplotypes observed in each of the French, Danish and Swedish populations, compared to the one haplotype in the UK population of a similar size, is an important factor accounting for the absence of association between HD and the DNA markers in these populations. Furthermore, these data are in favour of multiple independent origins for the mutation causing HD. PMID- 8370148 TI - Intrafamilial variability in the clinical expression of familial hypercholesterolemia: importance of risk factor determination for genetic counselling. AB - A specific mutation in the low-density lipoprotein receptor (LDLR) gene causes familial hypercholesterolemia (FH) in about 60% of Afrikaner FH heterozygotes. Molecular diagnosis of this so-called FH Afrikaner-1 mutation was performed in a family with the disease. One individual did not develop coronary heart disease (CHD) by age 84, despite having the FH Afrikaner-1 mutation, while his son who inherited the same gene, developed CHD before age 50 and had to undergo bypass surgery. All the sibs in the third generation inherited the defective LDLR gene allele. This variation in clinical presentation creates a counselling dilemma. It also raises questions about the effect of diet and life style, and the possibility of other genes either contributing to the severity of the disease, or protecting against high lipid levels in plasma. An investigation of the influence of selected factors on the clinical expression of the FH Afrikaner-1 mutation in this family indicated that it was especially the elevated apolipoprotein (a) levels, in addition to low levels of high density lipoprotein cholesterol and raised triglyceride and apolipoprotein B levels, that were associated with a greater risk of developing CHD. These findings are thus in accordance with the view that the severity of CHD in FH patients is not only determined by nature of the gene defect, but is also influenced by other risk factors. PMID- 8370149 TI - Distal arthrogryposis with autosomal dominant inheritance and reduced penetrance in females: the Gordon syndrome. AB - A family is reported in which camptodactyly, club foot, pectus excavatum and undescended testes are transmitted as an autosomal dominant with reduced penetrance and variable expressivity, affecting 13 members through five generations. Penetrance is more reduced in females than in males and asymptomatic carriers are always females. Similar findings were previously described in two other families reported by Gordon et al. (1962) and Halal & Fraser (1979). PMID- 8370150 TI - Marden-Walker syndrome: case report, literature review and nosologic discussion. AB - The Marden-Walker syndrome is characterized by psychomotor retardation, a mask like face with blepharophimosis, micrognathia and a high-arched or cleft palate, low-set ears, kyphoscoliosis and joint contractures. We report on a male patient with the clinical features of the syndrome. In addition, he had a Dandy-Walker malformation with hydrocephalus and vertebral abnormalities. During pregnancy, there were feeble fetal movements and polyhydramnios. We propose that Marden Walker syndrome is one of the etiologic possibilities in children with the heterogeneous fetal a(hypo)kinesia deformation sequence (FADS). Differential diagnosis is discussed. The etiology is probably heterogeneous. PMID- 8370151 TI - Evidence of chromosome 9 origin of the euchromatic variant band within 9qh. AB - Fluorescence in-situ hybridization studies using a whole chromosome 9 painting probe were performed on three individuals from two different families, who carry a chromosome 9 variant with an extra band within the elongated 9qh region. The results confirm the euchromatic nature of the extra band, and provide evidence that it is of chromosome 9 origin. This variant band, which may not be very rare, thus possibly results from a duplication of a segment of 9qh plus band p12 or part of band q21. PMID- 8370152 TI - Two siblings with mental retardation and progressive spasticity. PMID- 8370153 TI - Inheritance of intrahepatic cholestasis of pregnancy in one kindred. AB - We report three sisters with intrahepatic cholestasis of pregnancy (ICP) and the pedigree of the family, including six generations. ICP was observed in five successive generations; most of the patients also had cholelithiasis. The uniform expression, the complete penetrance of the trait and the direct parent-to-child transmission support the Mendelian dominant mode of inheritance. Determination of HLA A, B and C haplotype was made in five ICP patients, without any findings of HLA type common to everyone. X-linked inheritance cannot be excluded in this study. PMID- 8370154 TI - A retrospective CISS hybridization analysis of a case with de novo translocation t(18;22) resulting in an 18p- syndrome. AB - An unbalanced de novo translocation t(18;22) leading to a severely malformed liveborn girl with 18p- syndrome is described. Using the chromosomal in situ suppression (CISS) hybridization technique on 4-year-old G-banded chromosome preparations, it could be demonstrated that the translocation chromosome is composed of the long arm including the centromere of a chromosome 22 and the long arm of a chromosome 18. Consequently, the patient described here has lost the short arm including the centromere of chromosome 18. The possibility of restudying cytogenetically unsolved cases in clinical cytogenetics using older G banded chromosome preparations with the fluorescence in situ hybridization techniques is pointed out. PMID- 8370155 TI - Basilar impression and syringomyelia in a patient with tricho-rhino-phalangeal syndrome type I. PMID- 8370156 TI - Identical psychological profile and behaviour pattern in different types of mutation in the FMR-1 region. PMID- 8370157 TI - Clinical immunology: is it clinical science or medical practice? PMID- 8370158 TI - Immune stimulatory and anti-tumour properties of haemin. AB - IL-2 induces tumour regression in some patients with metastatic disease, but the dose of IL-2 is limited by severe toxicity. Agents that increase the expression of IL-2 receptors in the effector cells could be used to improve the effectiveness of IL-2 in mediating its anti-tumour effect. We have reported that haemin increased the expression of IL-2 receptors in human peripheral blood mononuclear cells (PBMC) and synergized with IL-2 in the induction of mitogenicity, cytotoxicity and cytokine production. We now report on haemin induced immune stimulation and tumour regression in mice. Haemin-induced mitogenicity in mouse splenocytes was potentiated up to two-fold by IL-2. The combination of haemin and IL-2 was also effective in inducing cytotoxicity for natural killer (NK)-resistant target cells. Maximal induction of cytotoxicity was attained at an optimal concentration of haemin of 10 microM. Higher concentrations were less effective. Splenocytes isolated from mice that had been treated in vivo with haemin and IL-2 incorporated twice the amount of 3H thymidine compared with splenocytes from mice treated with either haemin or IL-2 alone. Cytotoxicity of splenocytes for NK-resistant target cells was not increased following in vivo administration of haemin and IL-2 when fresh splenocytes were tested. Cytotoxicity was enhanced, however, up to five-fold following 48 h in vitro incubation with IL-2. Administration of haemin and IL-2 resulted in a significant decrease (40%) of established hepatic metastases in mice. Either IL-2 or haemin alone at the dose used were ineffective. The anti tumour effect of haemin and IL-2 was enhanced (63% decrease in metastases) by administration of the thiol compound, N-acetylcysteine. Since haemin can safely be administered to patients, it may represent a new class of biologic response modifiers that could enhance IL-2-mediated anti-tumour effects. PMID- 8370159 TI - Suppression of autoimmune disease in NZB/W F1 mice by treatment with the novel immunomodulator BTS 63155. AB - Autoimmune disease in NZB/W F1 mice was treated from 23 weeks of age with the novel immunomodulator BTS 63155 and, for comparative purposes, the established immunosuppressive agent cyclosporin A. Both drugs significantly improved survival compared with untreated controls. Lupus nephritis was also significantly reduced in the drug-treated groups, and this was related to reduced glomerular deposition of IgG. Autoantibody (ANA) levels were lowered by treatment with cyclosporin A, but not by BTS 63155. This latter finding may indicate a different mode of action for the two drugs. In a long term study, neither drug effected a complete cure, as autoimmune disease recurred on withdrawal of drug treatment. PMID- 8370160 TI - The anti-arthritic and immunosuppressive effects of cyclosporin A on collagen induced arthritis in the rhesus monkey. AB - The influence of cyclosporin A (CsA) on type II collagen-induced arthritis (CIA) in the rhesus monkey has been investigated. CsA was administered subcutaneously in a dose of 25 mg/kg per day during 9-18 days and additionally 12.5 mg/kg per day for 7 days. At this dosing regime no significant alterations of haematologic parameters were found, indicating that the toxicity of CsA was negligible. Administration of CsA after onset of arthritis had no beneficial effect, but when given between immunization and manifestation of clinical symptoms, CIA could be prevented completely. Moreover, these monkeys became resistant to the disease, because no arthritic activity could be observed upon a booster immunization with type II collagen (CII). The suppression of disease by CsA is reflected in reduced antibody levels to CII. PMID- 8370161 TI - Cyclosporin A increases the pulmonary eosinophilia induced by inhaled Aspergillus antigen in mice. AB - We evaluated the effects of anti-inflammatory drugs in a murine model of allergic bronchopulmonary aspergillosis (ABPA). Mice instilled with 100 micrograms of Aspergillus fumigatus antigen (intranasally, 3 days a week for 3 weeks) developed pulmonary lesions, characterized by a perivascular and peribronchial eosinophil infiltration, a bronchoalveolar lavage (BAL) eosinophilia, and elevated levels of total IgE, total IgG1 and A. fumigatus-specific IgG1. Under the same conditions, groups of mice receiving a daily dose of 2 mg/kg dexamethasone showed decreased numbers of eosinophils and total cells in BAL, had less numerous eosinophils in their pulmonary infiltrates, and had lower levels of serum and BAL fluid total IgE, total IgG1 and A. fumigatus-specific IgG1. Conversely, groups of mice pretreated with an immunosuppressive agent, cyclosporin A (CsA) at a dose of 50 mg/kg, three times per week, developed pulmonary lesions with enhanced lung eosinophilic influx and increased total IgE levels, both in serum and in BAL fluid. These findings show that dexamethasone potently prevents the murine immunopathologic response to A. fumigatus. The effect of CsA on this inflammatory response was paradoxical, insofar as it suggests an activation of the T helper 2 subset, which up-regulates eosinophil recruitment and IgE production. PMID- 8370162 TI - A longitudinal study of the IgG antibody response to HIV-1 p17 gag protein in HIV 1+ patients with haemophilia: titre and avidity. AB - The IgG response to HIV-1 p17 gag protein was studied for up to 6 years in 12 HIV 1-infected patients with haemophilia, who had seroconverted between 1982 and 1985. To assess any prognostic value, p17 IgG titres were compared with p24 IgG titres, CD4 cell counts and p24 antigenaemia. p17 IgG avidity index was also examined. A strong similarity was found between the IgG titre to HIV-1 p17 and that to p24. In patients who developed AIDS the decline in p17 IgG titres could precede by several years the drop in CD4 cells to under 200 cells/microliters; whereas some long-term asymptomatic patients (CDCII) had increasing p17 IgG titres and stable CD4 cell counts. Declining p17 and p24 IgG titres were not always associated with an increase in p24 antigenaemia. IgG titres were found to be better predictors of disease progression than CD4 cell counts or p24 antigenaemia. Patients who developed AIDS during the study were also characterized by a lower p17 IgG avidity than patients who remained asymptomatic. This result suggests that IgG avidity could have prognostic relevance and be of importance for host resistance to AIDS onset. PMID- 8370163 TI - Immunogenicity of the meningococcal stress protein MSP63 during natural infection. AB - Acute- and convalescent-phase sera from 40 patients with meningococcal disease were evaluated for immunoreactivity with the meningococcal member of the hsp60 stress protein family. The IgG response was measured by ELISA, using bacterial cell lysate of the corresponding patients' strain, and purified hsp60 proteins from Neisseria meningitidis (MSP63), Escherichia coli (GroEL) and Mycobacterium bovis BCG (65K) as antigens. Analysis of the antibody responses revealed that 24/35 patients (69%) with elevated anti-meningococcal titres, generated anti MSP63 antibodies during the time course of infection. Twelve of these patients generated antibodies specific for MSP63, in six patients anti-MSP63 levels exceeded anti-GroEL/65K antibodies. In the remaining six patients, equal levels of anti-MSP63 and anti-GroEL/65K were measured. We conclude that MSP63 is expressed and immunogenic during natural meningococcal infection, and that individual subjects have a restricted response to the antigen, resulting in the recognition of Neisseria-specific hsp60 epitopes and/or cross-reactive hsp60 determinants. PMID- 8370164 TI - Successful primate immunization with peptides conjugated to purified protein derivative or mycobacterial heat shock proteins in the absence of adjuvants. AB - We have previously shown in mice that antibodies can be induced to synthetic malaria peptides conjugated to mycobacterial antigens, such as purified protein derivative (PPD) or heat shock proteins (hsp), and given in the absence of adjuvants after a previous priming with bacille Calmette-Guerin (BCG). In the present study we investigated this model of immunization in the non-human primates, Saimiri sciureus monkeys. Monkeys primed with BCG subcutaneously and then immunized subcutaneously with the Plasmodium falciparum sporozoite (NANP)40 synthetic peptide conjugated to PPD or mycobacterial hsp of 65 or 70 kD, in the absence of adjuvants, produced antipeptide and anti-sporozoite IgG antibodies. Interestingly, the carrier effect of the hsp of 70 kD for the induction of anti (NANP)40 antibodies was also observed in the absence of a previous priming with BCG. These data suggest that such a vaccination strategy may be applied to humans. PMID- 8370165 TI - Contrasting levels of in vitro cytokine production by rheumatoid synovial tissues demonstrating different patterns of mononuclear cell infiltration. AB - Synovial membrane samples obtained at knee arthroplasty from 22 patients with rheumatoid arthritis (RA) were characterized histologically. Two groups were identified. Tissue samples from 15 patients demonstrated multiple focal lymphoid aggregates of mononuclear cells (group A). Samples from the remaining seven patients demonstrated diffuse mononuclear cell infiltration (group B). Samples of each synovial membrane (0.25 g) were cultured for cytokine production. The highest levels of IL-1 beta and IL-6 were produced by group A tissues: 19.1 +/- 19.6 ng/ml IL-1 beta (mean +/- s.d.) and 264.4 +/- 301.9 ng/ml IL-6, versus 3.8 +/- 6.6 ng/ml and 54.7 +/- 42.6 ng/ml respectively. Small quantities of IL-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P = 0.04). Moreover, using MoAbs, the most intense cytokine staining in the tissues was detected in group A. Similar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both groups. It is suggested that the presence of multiple focal lymphoid aggregates associated with higher levels of cytokine production observed in group A represent a greater degree of immunological activation, and may represent a subgroup of patients with a greater potential for articular destruction. PMID- 8370166 TI - Antibody penetration of viable human cells. II. Anti-RNP antibodies binding to RNP antigen expressed on cell surface, which may mediate the antibody internalization. AB - As U1 small nuclear ribonucleoprotein (U1 snRNP2) has a crucial role in pre-mRNP splicing, the interaction of anti-RNP antibody with snRNP within viable lymphocytes may profoundly influence cell functions. We have shown that antibody can penetrate viable human lymphocytes, and anti-RNP antibodies enter more cells than other anti-nuclear antibodies or control IgG. In order to study the in vitro interaction of anti-RNP antibodies with viable cells, T lymphocytes were metabolically labelled with 35S-methionine, then incubated with the antibodies and washed. A set of 35S-labelled cell-associated snRNP polypeptides A, B'/B, C and D were found to bind to both monospecific human polyclonal anti-RNP IgG (human anti-RNP IgG) and a mouse monoclonal anti-RNP antibody (2.73), indicating that anti-RNP antibodies interacted with RNP antigen inside or/and on the surface of viable cells. To investigate antibody binding to RNP antigen on the cell surface, the cell surface proteins were either iodinated with 125I or the cells processed for immunoelectron microscopic studies after incubation with MoAb. At least seven 125I-labelled polypeptides on the cell surface were found to be immunoprecipitated by the anti-RNP MoAb which have similar molecular weights to U snRNP polypeptides 70K, A, B, D, E, F, and G. The immunoelectron microscopic studies showed that the gold particles formed clustered patches on the cell membrane. Further studies suggested that RNP antigen bound to the cell surface, and the RNP binding structure was probably a heterodimer receptor. This study provides evidence to suggest that anti-RNP antibody entry into viable cells may be mediated by interaction with RNP antigen expressed on the cell surface. PMID- 8370167 TI - Relevance of classic anti-neutrophil cytoplasmic autoantibody (C-ANCA)-mediated inhibition of proteinase 3-alpha 1-antitrypsin complexation to disease activity in Wegener's granulomatosis. AB - In the sera of patients with Wegener's granulomatosis (WG), C-ANCA can be detected that are directed against proteinase 3 (PR3). We have previously observed that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3 with its major physiologic inhibitor, alpha 1-antitrypsin (alpha 1AT). In the present study we investigated whether this inhibitory effect of C-ANCA on PR3-alpha 1AT complexation correlates with clinical activity of WG. Serial serum samples of eight consecutive patients with histologically proven relapses of WG were tested. At the moment of relapse all sera revealed inhibitory activity towards PR3-alpha 1AT complexation (median 22%, range 10-59%). Disease activity score (r = 0.87, P < 0.02) and C-reactive protein (CRP) levels (r = 0.66, P < 0.1) correlated with C-ANCA inhibition of PR3-alpha 1AT complexation, while they did not correlate with the C-ANCA titre detected by indirect immunofluorescence (IIF) nor with IgG anti-PR3 antibody level measured by ELISA. The inhibitory effect of C-ANCA on PR3-alpha 1AT complexation had risen significantly at the moment of relapse compared with values 3 months (P < 0.05) and 6 months (P < 0.01) before relapse. Eight patients with established WG and positive for C-ANCA but without clinical evidence of relapse served as controls. In this group no inhibitory effect of C-ANCA on PR3-alpha 1AT complexation was observed in 7/8 patients sera. Sera of one control patient contained moderate C ANCA inhibitory activity towards PR3-alpha 1AT complexation, which remained at a constant level during the 6 months period of observation. Thus, disease activity in WG appears to be more closely related to C-ANCA inhibitory activity towards PR3-alpha 1AT complexation. PMID- 8370168 TI - C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells. AB - The glomerular mesangial cell (GMC) plays a key role in the maintenance of glomerular structure and function and in the mediation of glomerular injury. To explore the potential of this cell to produce complement and react to local inflammatory signals, we studied the synthesis and regulation of the third and fourth components of complement in cultured human GMC. Using metabolic labelling and immunoprecipitation, we found that C3 and C4 polypeptide chains were synthesized and secreted by GMC. Interferon-gamma (IFN-gamma) led to an increase in C4 protein synthesis, but not C3 synthesis. There was a corresponding increase in C4 mRNA in IFN-gamma-activated cells, but no increase in C3 mRNA, as determined by semi-quantitative polymerase chain reaction (PCR) estimation. These results demonstrate that human GMC can synthesize C3 and C4 proteins, and that regulation of expression of the C4 gene is mediated by IFN-gamma. We hypothesize that GMC production of complement could influence the clearance of immune aggregates by the kidney and the mediation of glomerular injury. PMID- 8370169 TI - Serum glomerular binding activity is highly correlated with renal disease in MRL/lpr mice. AB - The pathogenesis of lupus nephritis is felt to be mediated by anti-DNA antibodies. However, the anti-DNA response and renal disease do not entirely correspond. We recently developed a new assay which detects immune elements based on their ability to bind glomeruli as an alternative approach to understanding the pathogenesis of this disorder. The glomerular binding activity (GBA) defined by this assay consists of immune elements containing IgG which interact specifically with renal tissue, the binding of which is DNase-inhibitable, but which do not bind to DNA directly. In the current study we assessed the relationship between GBA and renal disease in MRL/lpr mice (both untreated and cyclophosphamide-treated) and compared it with the anti-DNA assay. Both assays were highly correlated with renal disease in untreated mice in terms of proteinuria. In cyclophosphamide-treated mice, however, only a weak correlation between the anti-DNA assay and proteinuria was apparent. GBA, in contrast, was more strongly correlated with proteinuria in treated mice. This correlation improved substantially when the DNase-sensitive component of the GBA was used. GBA appeared related to, but not covariant with, the anti-DNA response. These results demonstrate that GBA is a better correlate of murine lupus nephritis than the anti-DNA assay, and suggest that the immune elements detected by this assay, the DNase-sensitive component in particular, may be pathogenically important. PMID- 8370170 TI - The paraproteins in systemic capillary leak syndrome. AB - Systemic capillary leak syndrome (SCLS) is a rare disease characterized by episodes of collapse due to rapid transfer of considerable volumes of plasma from the intravascular to the extravascular compartment. The pathogenesis of this disease is unknown. The diagnosis is made largely on clinical grounds, and investigations are unhelpful. The only consistent abnormality is that an IgG paraprotein is found in most patients, raising the possibility that the paraprotein may be involved in the pathogenesis of the disease. Reduction of the paraprotein level in our patient was associated with remission. Blood samples from three SCLS patients and one probable SCLS have been studied. All patients had monoclonal IgG paraproteins. The purified paraproteins were all of IgG1 subclass and had kappa light chains. However, they differed in size and charge. Antibodies against each of the paraproteins were raised in rabbits. Affinity purified anti-idiotypic antibodies were tested for cross-reactivity against the other paraproteins using immunoblotting and Ouchterlony assay. These assays showed that the anti-idiotypic antibodies reacted only with the immunizing paraprotein and not with any of the other paraproteins, i.e. that the paraproteins do not share a common idiotype. Paraproteins did not bind to cultured endothelial cells, either unactivated or following activation with interferon-gamma (IFN-gamma), IL-2 or IL-6. In addition, we were unable to demonstrate any cytotoxicity towards cultured human endothelial cells by paraprotein alone, or in the presence of neutrophils (pronounced neutrophilia being a feature of attacks). The relationship between the paraproteins and the disease remains unclear. It is likely that additional, as yet unidentified, factors are required for the paraprotein to lead to capillary leak. PMID- 8370171 TI - Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease. AB - Intrathyroidal lymphocyte subsets were analysed in 13 euthyroid patients with autoimmune thyroid disease by two-colour flow cytometry and compared with subsets in peripheral blood. In both Graves' and Hashimoto's diseases, proportions of intrathyroidal CD5- B cells were higher than in peripheral blood. The numbers of such cells were correlated with serum levels of anti-thyroid microsomal antibodies. Proportions of T cells bearing alpha beta chains of T cell receptors (TCR alpha beta+ T; T alpha beta) and CD16+CD57+ natural killer (NK) cells were lower in the thyroid, but proportions of CD3hiTCR alpha beta-TCR gamma delta+ (T gamma delta) cells were not different. Proportions of CD4+Leu-8- helper T cells and CD4+CD57+ germinal centre T cells were higher and proportions of CD4+Leu-8+ suppressor-inducer T cells and CD8+CD57+ or CD8+CD11b+ suppressor T cells were lower than in the blood in both diseases. Proportions of CD5+ B cells were high in Graves' disease, and proportions of CD8+CD11b- cytotoxic T cells were high in Hashimoto's disease. Unexpectedly, CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4 CD8- cells were present in thyroid tissues of both diseases. These findings suggest that: (i) an imbalance in the numbers of regulatory T cells and of NK cells that had appeared in the thyroid resulted in the proliferation of CD5- B cells, which were related to thyroid autoantibody production; (ii) CD5+ B cells and cytotoxic T cells are important for the different pathological features in Graves' and Hashimoto's diseases, respectively; and (iii) intrathyroidal CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells may be related to the pathogenesis of autoimmune thyroid disease. PMID- 8370172 TI - The presence of immunosuppressive 'p15E-like' factors in the serum and urine of patients suffering from malign and benign breast tumours. AB - Certain types of tumours are capable of producing factors inhibiting mononuclear phagocyte chemotaxis which may contribute to defects in immunosurveillance. In head and neck cancer these factors are said to be related to the retroviral protein p15E. This study examines the presence of p15E-like factors in serum and urine of patients with malign and benign breast tumours. Thirty patients with breast cancer, 29 patients with benign breast masses, and 28 healthy controls were tested blindly with the monocyte polarization assay, using N-formyl methionyl-leucylphenylalanine as chemo-attractant. The low molecular weight fractions prepared of sera of the malign tumour patients inhibited the monocyte polarization significantly (mean inhibition 34%, s.d. = 12) compared with those of benign tumour patients (15%, s.d. = 7) and of controls (14%, s.d. = 6). The observed inhibitory effects on the monocyte polarization could be compensated by MoAbs reactive to p15E-related antigens. The mean difference between the polarization inhibition with and without anti-p15E adsorption (the 'p15E-like factor-induced inhibition') was 25% (s.d. = 13) in the breast cancer group, compared with 7% (s.d. = 5) in the benign tumour patients and 5% (s.d. = 4) in the healthy control group. Surgical removal of the tumours resulted in a restoration of the monocyte polarization in 20/23 (87%) patients of the breast cancer group. Results testing preoperative urine samples correlated well with those of corresponding sera. These data give additional support to the concept that tumour-derived p15E-like factors are responsible for the inhibitory effect on monocyte chemotaxis in breast cancer patients, and that these factors can be found in serum as well as in urine. PMID- 8370173 TI - Functional analysis of TCR gamma delta+ T cells in tumour-infiltrating lymphocytes (TIL) of human pancreatic cancer. AB - In six patients with advanced pancreatic carcinoma, TIL and tumour-draining lymphocytes (TDL) were isolated from primary pancreatic tumour and regional lymph nodes. In comparison with TDL and peripheral blood lymphocytes (PBL), TIL contained a comparatively higher percentage of TCR gamma delta+ cells, although they were still a small fraction. By 2 weeks culture with rIL-2 and immobilized OKT-3 antibody, the TCR gamma delta+ cells in TIL were preferentially expanded at the early culture periods, although it was temporary. In four cases, the TCR gamma delta+ and CD8+ TCR alpha beta+ TIL were separated by negative sorting using flowcytometry. All the TCR gamma delta+ TIL were CD4-, CD8- (double negative), and one of the TIL lines was mostly composed of delta TCS1+ cells, while the others were delta TCS1-. In comparison with CD8+ TCR alpha beta+ TIL, all the TCR gamma delta+ TIL exhibited much stronger lytic activity against freshly isolated autologous pancreatic cancer cells. However, all the gamma delta+ TIL also exhibited a strong non-MHC-restricted cytotoxicity, and there was no correlation between the lytic pattern and the percentage of delta TCS1+ cells. These data suggest that the TCR gamma delta+ T cells can proliferate vigorously in a certain condition, and if successfully expanded in vitro they might be helpful material for effective adoptive immunotherapy. PMID- 8370174 TI - Expression of cytokine genes in human cardiac allografts: correlation of IL-6 and transforming growth factor-beta (TGF-beta) with histological rejection. AB - Cytokines may play critical roles in allograft rejection. Currently, a clear pattern of cytokine production that correlates with rejection has not emerged. Our preliminary studies suggested a trend toward increased IL-6 and TGF-beta gene expression in cardiac allografts during rejection. We have extended these studies using reverse transcriptase/polymerase chain reaction (RT/PCR) to detect the expression of IL-6, TGF-beta, and T cell receptor beta chain constant region (TCR beta) genes in 21 additional consecutive myocardial biopsies obtained from six heart transplant patients and from five pre-transplant donor hearts. Cytokine gene expression was compared with histological diagnosis of rejection. There was strong correlation between IL-6 as well as TGF-beta gene expression, and histological rejection (6/8 biopsies with versus 0/7 without rejection (P = 0.006) and 7/9 biopsies with versus 0/7 without rejection (P = 0.003) respectively). Neither IL-6 nor TGF-beta transcripts were detected in any pre transplant donor heart. TCR-beta chain mRNA was found in all allograft biopsies regardless of the presence of rejection, but was absent in pre-transplant donor hearts. Our results indicate that expression of IL-6 and TGF-beta is highly correlated with allograft rejection and thus may play an important role in regulation of cardiac allograft rejection. T cell infiltration of allografted myocardium is invariably detected by PCR regardless of histological rejection. The long-term functional significance of these cells in transplanted hearts needs further investigation. PMID- 8370175 TI - IgG inhibits the increase of platelet-associated C3 stimulated by anti-platelet antibodies. AB - We investigated the increase of platelet-associated IgG and complement component 3 (C3) caused by the in vitro action of anti-platelet MoAbs, and the effect of mouse and human IgG on these events. Anti-glycoprotein IIb/IIIa and anti glycoprotein Ib MoAbs caused a slight increase of C3, but not of platelet associated IgG. In contrast, anti-CD9 and anti-Fc gamma II receptor MoAbs caused an increase of both platelet-associated C3 and IgG. In particular, three MoAbs which activated the complement system caused a marked increase of C3. When platelet-rich plasma was treated with aspirin and prostaglandin E1 before incubation with antibodies, the increase of platelet-associated IgG was inhibited in all cases. In contrast, the increase of platelet-associated C3 was scarcely influenced. These results suggest that the binding to platelets of platelet activating antibodies caused the increased expression of IgG molecules on the platelet surface and a possible increase of platelet-associated IgG. However, the increase of platelet-associated C3 appeared to depend on specific characteristics of the antibodies tested, such as a complement-activating effect. In addition, intact mouse or human IgG inhibited the increase of platelet-associated C3 caused by complement-activating antibodies, while F(ab')2 mouse or human IgG had no such effect. This suggested that the Fc portion of IgG may block the increase of C3 mediated by anti-platelet antibodies. PMID- 8370176 TI - Definition of unique traits of human CD4-CD8- alpha beta T cells. AB - We have studied the nature of human CD4-CD8- (double negative) alpha beta T cells to determine whether they possess unique characteristics which could further differentiate them from conventional CD4+ or CD8+ (single positive) T cells. We observed that double negative TCR alpha beta+ T cells differ from single positive T cells in the following respects: (i) their T cell receptor (TCR) repertoire is different, as revealed by the analysis of 47 clones derived from three individuals and by analysis of peripheral blood lymphocytes (PBL) prior to in vitro manipulation; (ii) their in vivo CD3:TCR expression is lower before in vitro manipulation and expansion; (iii) their direct proliferative response to IL 3, which is not mediated by secondary release of other T cell growth factors. These characteristics have also been recently ascribed to murine double negative alpha beta T cells, which develop extrathymically and are considered to be a distinct T cell lineage. Our data suggest that, like their murine counterparts, human double negative alpha beta T cells may represent a distinct T cell lineage which might develop extrathymically. PMID- 8370179 TI - Clinical immunology: guidelines for its organization, training and certification; relationships with allergology and other medical disciplines--a WHO/IUIS/IAACI report. PMID- 8370178 TI - IL-2 receptor gene expression and IL-2 production by human preterm newborns' cells. AB - IL-2 receptor (IL-2R) gene expression in human umbilical cord blood mononuclear cells (CBMC) of preterm and term newborns was examined following stimulation for 18 h with phytohaemagglutinin (PHA) and compared with that of adult peripheral blood mononuclear cells (PBMC; mothers and control group). mRNA for IL-2R could not be detected in CBMC of preterm infants, whereas the mRNA levels for IL-2R found in full term neonates were similar to those observed in PBMC of adults. IL 2 activity in conditioned medium (CM) of mononuclear cells stimulated with either optimal or suboptimal PHA concentrations for 24 h and 48 h was also determined. At 24 h of stimulation, IL-2 activity found in CM obtained from CBMC of preterm and term newborns was significantly higher than that found in CM of adults' PBMC. A further enhancement of IL-2 activity (six to eight times) was observed in CM of preterm and term cells stimulated for 48 h, whereas no significant difference was found in IL-2 activity in CM from adult cells tested at the two incubation periods. The present findings may provide an additional explanation for the impaired function of the immune system, and the high susceptibility to infections observed in preterm newborns. PMID- 8370177 TI - Interaction of IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in human T cells activated by murine antigens. AB - We used a mixed leucocyte culture between human T cells and irradiated murine splenocytes which allowed us to distinguish between cytokine production from the responder and stimulator cells by the use of species-specific assays for mRNA up regulation. Using this model of T cell activation by antigen, we studied the effects of human antigen-presenting cell-derived cytokines IL-1 beta, IL-6 and TNF-alpha on the activation of human T cell subsets. We show in this system that exogenously added IL-1 beta, IL-6 and TNF-alpha induces IL-2 receptor (R) up regulation and IL-2 production, and proliferation by both CD4+ and CD8+ cells. The addition of IL-1 beta induces IL-6 mRNA, and anti-IL-1 antibodies or an IL-1R antagonist protein completely suppresses IL-6 and TNF-alpha supported proliferation. Similarly, addition of IL-6 or TNF-alpha induces up-regulation of IL-1 beta mRNA. However, anti-IL-6 and anti-IL-6R antibodies only partially block proliferation supported by IL-1 beta. These findings suggest that IL-6 and TNF alpha will induce IL-2R up-regulation/IL-2 secretion via the induction of IL-1 beta production. PMID- 8370180 TI - SART stress effects on lymphocytes in the thymus and spleen of normal, adrenalectomized, and sympathectomized mice. AB - The effects of stress due to specific alteration of rhythm of temperature (SART) on lymphocyte subpopulations of the thymus and spleen were examined in C3H/He mice. Thymic and splenic involution were evident in SART-stressed mice, and lymphocyte subpopulations were significantly changed. In the thymus, CD4+ CD8+ and CD3- or CD3low lymphocytes were decreased by SART stress more than other lymphocytes, and CD4- and CD8-single-positive lymphocytes and B lymphocytes in the spleen were decreased equally. Immunoregulation via the adrenal glands and sympathetic nervous system was studied in chemically sympathectomized and adrenalectomized SART-stressed mice. Neither chemical sympathectomy nor adrenalectomy alone influenced the thymus or spleen in nonstressed mice, but chemical sympathectomy enhanced SART stress-induced thymic changes and further decreased the number of B lymphocytes in the spleen of SART-stressed mice; adrenalectomy blocked SART stress-induced thymic changes and increased the number of B lymphocytes in the spleen. These findings indicate that the genesis of thymic changes induced by SART stress is in the adrenal glands, and malfunction of sympathetic nerves and insufficient excretion of adrenal hormones could alter the balance of lymphocytes in the spleen during stress. It was also clear that thymic changes induced by SART stress could be immediately reversed to pretest conditions by alleviating the stress. PMID- 8370181 TI - Effects of adoptive immunotherapy with autologous CD8+ T lymphocytes on immunologic parameters: lymphocyte subsets and cytotoxic activity. AB - CD8+ cytotoxic T lymphocytes (CTL) may be an important parameter of host resistance to HIV infection. The present study determined whether CD8+ cells could be purified and propagated in vitro to enhance anti-HIV CTL activity, and the immunologic effects of infusion of these cells into autologous, HIV-infected patients as a potential immunotherapy for AIDS and AIDS-related complex (ARC). CD8+ lymphocytes from five AIDS and ARC patients were purified from leukapheresis preparations in cell culture flasks coated with CD8-specific monoclonal antibodies and propagated in vitro for 3 weeks. The ex vivo propagated cells were 98% (+/- 1%) CD8+ and 43% (+/- 6%) HLA-DR+. The majority of the CD8+ cell preparations had increased lytic activity against autologous B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-IIIb structural proteins gag, pol, or env, relative to that of fresh blood mononuclear cells tested prior to purification and culture. The results also show for the first time that CD8+ CTL from HIV-infected patients can lyse cells expressing the HIV regulatory protein, tat. Enhanced expression of CD56 (natural killer cell marker) and lytic activity against vaccinia virus control vector-infected, autologous targets were also noted in the CD8+ cell preparations. Infusion of the CD8+ CTL into autologous patients was well-tolerated and resulted in low but discernible, temporal increases in circulating cytotoxic activity against the HIV gene expressing targets. PMID- 8370182 TI - Induction of immune-mediated glomerulonephritis in normal mice immunized with bacterial DNA. AB - Normal mice immunized with bacterial DNA produce high titers of anti-DNA antibodies and represent a new model for autoantibody production in systemic lupus erythematosus. To determine whether DNA immunization can also provoke clinical manifestations of lupus, the occurrence of nephritis in immunized mice was assessed and correlated with levels of anti-DNA as well as antibodies to glomerular antigens. BALB/c mice immunized with Escherichia coli single-stranded DNA in complexes with methylated bovine serum albumin in adjuvant showed increased proteinuria compared to control mice immunized with mBSA alone. Furthermore, DNA immunized mice had significantly greater glomerular proliferative changes and immunoglobulin deposition than control mice. In an in vitro assay, sera from DNA immunized mice exhibited greater binding to glomerular antigens than sera from control mice. Compared to sera, renal eluates from DNA immunized mice were enriched for anti-DNA and glomerular binding activity. These data indicate that immunization of normal mice with E. coli DNA induces an immune mediated proliferative glomerulonephritis that is likely secondary to the renal deposition of anti-DNA antibodies. PMID- 8370183 TI - Modulation of MHC expression on human endothelial cells by sera from patients with systemic lupus erythematosus. AB - Major histocompatibility complex (MHC) antigen expression on cells is a prerequisite for immune interaction with activated T-cells. This study examined the ability of sera from patients with systemic lupus erythematosus (SLE) to modulate MHC expression on vascular endothelial cells. SLE sera were able to selectively upregulate MHC class I antigen expression on cultured human umbilical venous endothelial (HUVE) cells, without concomitant induction of MHC class II antigen. The stimulation index (SI) for MHC class I expression produced by SLE sera (1.21 +/- 0.23) was significantly higher than those for normal controls (1.01 +/- 0.10) (P < 0.0001) and non-SLE patients (1.12 +/- 0.14) (P < 0.05). Additionally, active SLE patients had higher mean SI than inactive patients (P < 0.001). Preincubation of SLE sera with Protein A-Sepharose beads conjugated with antibodies against tumor necrosis factor-alpha and interferon-alpha was able to significantly reduce their ability to upregulate class I MHC expression by HUVE cells, indicating that these cytokines were responsible for the modulatory effect. This could be an important mechanism for the immune-mediated vascular injury seen in SLE. PMID- 8370184 TI - Decreased activity of complement-mediated immune complex clearance in hemodialysis patients. AB - Complement-mediated immune complex (IC) clearance was examined in the sera from regular hemodialysis patients, who accumulated excess factor D in the circulation. Both complement activities for the inhibition of insoluble IC formation and the solubilization of insoluble IC were lower in the sera from these patients than in the sera from normal individuals. A similar decrease in complement activities was observed in normal serum fortified with excess factor D. In addition, complement-processed IC was found to be bound less effectively to human erythrocytes via complement receptor type 1 in the sera from these patients and from normal serum fortified with excess factor D than in normal serum. Gel filtration HPLC analysis revealed a decrease in covalent binding of C3 fragments to IC solubilized in the sera from hemodialysis patients or in normal serum fortified with excess factor D. This supports the notion that lower complement mediated IC clearance is due to the paucity of complement fragments bound to IC. It is suggested that some detrimental alterations in the complement system, probably due to excess factor D, cause decreased IC clearance activity in hemodialysis patients with chronic renal failure. PMID- 8370185 TI - Immunohistochemical localization of intracellular and extracellular associated TGF beta in the skin of patients with systemic sclerosis (scleroderma) and primary Raynaud's phenomenon. AB - We have investigated the distribution of TGF beta using antibodies specific for its intracellular and extracellular forms in full-thickness biopsies of patients with SSc, primary Raynaud's phenomenon (PRP), systemic lupus erythematosus (SLE), and from normal subjects. Nine of 11 SSc biopsies demonstrated intracellular TGF beta in endothelial cells while only 6 exhibited extracellular TGF beta. Endothelial cells in skin biopsies of all PRP patients displayed both intracellular and extracellular TGF beta. All other control biopsies were negative. In patients with PRP, some positively staining fibroblasts were found scattered throughout the dermis. Lastly, extracellular TGF beta was localized in the papillary dermis of PRP and SSc biopsies and in all the dermal layers of SLE patients. No significant staining of TGF beta was observed in the endothelial cells, fibroblasts, or in the extracellular matrix of the majority of biopsies from normal subjects. These data suggest that TGF beta may be one of the cytokines involved in the early stages of pathogenesis of SSc, and that endothelial cells in SSc and PRP may be a source and/or a target of TGF beta. PMID- 8370186 TI - Characterization of antinuclear autoantibodies present in the serum from nonobese diabetic (NOD) mice. AB - The nonobese diabetic (NOD) mouse develops insulin-dependent type 1 diabetes in response to autoantibodies and T-cell attack directed against pancreatic islet cell antigens. Sera obtained from nondiabetic and diabetic female mice demonstrated a 1.4-fold increase in IgG levels when compared to BALB/c control animals. Nondiabetic and diabetic male mice had a 2.1- and 3-fold increase, respectively, in serum IgG levels over that of control mice. Seven of 11 non diabetic and 7/10 diabetic sera from female NOD mice contained antibody to cytoplasmic or nuclear components of HEp-2 cells. Cytoplasmic staining revealed reaction against cytoskeletal and midbody structures. Punctate nuclear staining patterns with HEp-2 cells showed antibody reaction to the centriole, mitotic chromosomes, and nuclear rim. On the other hand, sera from BALB/c mice were negative for antibody staining of HEp-2 cells. Confirmation of the autoantibody nature of the NOD sera was obtained by antibody staining of nuclear structures from the mouse 3T3 fibroblast cell line, and by staining of salivary gland tissue sections. The nuclear and cytoplasmic staining patterns of diabetic NOD sera were reminiscent of the autoantibody staining patterns observed in Sjogren's syndrome and other inflammatory autoimmune connective tissue diseases. PMID- 8370187 TI - In vivo effects of thymustimulin on hematopoiesis of mice treated with cyclophosphamide. AB - This study reports on the in vivo effects of thymustimulin (TST), a thymic extract, on the hematopoiesis of mice treated with cyclophosphamide (CTX). Peripheral blood counts and both bone marrow pluripotent (spleen colony-forming units, CFU-S) and committed (granulocyte-macrophage colony-forming units, CFU-GM; erythroid burst-forming units, BFU-E) hematopoietic progenitor cells were assayed by in vitro methods. Administration of CTX alone was associated with severe hemotoxicity, which was followed by a gradual recovery of hematopoiesis. Hematotoxic effect of CTX was less pronounced when TST was administered in association with CTX. All the studied parameters were higher in TST + CTX-treated animals than those in CTX-treated animals, especially after Day 5 from the beginning of treatment for blood leukocytes, bone marrow cell counts, and packed red cell volume, and at Day 10 or 15 for CFU-S, CFU-GM, and BFU-E. These findings suggest that, in this experimental model, the simultaneous administration of TST reduces the myelosuppressive activity of CTX in vivo. PMID- 8370188 TI - Balloon dilatation of inferior vena cava obstruction in Budd-Chiari syndrome. PMID- 8370189 TI - Interventional techniques for the management of coronary artery lesions: an update. AB - Coronary balloon angioplasty has become standard treatment for ischemic coronary artery disease. Major limitations of angioplasty are the inferior results obtained with unfavorable lesions, the occurrence of abrupt occlusion responsible for in-hospital mortality and morbidity, and the high restenosis rate at 6 months. New techniques for stents, laser, and atherectomy have been developed to overcome these limitations. Until now, although the initial results are encouraging, these new techniques have not as yet shown to be clearly superior to balloon angioplasty. However, due to the limitations of balloon angioplasty, further development of new techniques should be stimulated so that nonsurgical treatment of coronary artery disease will become safer, more effective, and applicable to a wider spectrum of coronary artery disease. PMID- 8370190 TI - Transesophageal echocardiography: increased risk by repeated attempts to insert the transducer in patients with coronary artery disease? AB - The question of whether several attempts at transducer insertion increase the risk of performing transesophageal echocardiography (TEE) in patients with coronary artery disease (CAD) has not been addressed to date. In the course of performing TEE in 45 patients with CAD, two or more attempts to insert the transducer were necessary in 9 cases. During various attempts, heart rate, blood pressure and ST-segment depression were recorded and correlated with the findings of the exercise electrocardiogram (ECG) and coronary angiography. Insertion was successful in six patients after two attempts and in three other patients after three, four, and five attempts, respectively. Heart rate rose significantly (p < 0.005) with the increase of insertion attempts. In one patient, it continued to rise at the fourth attempt, reaching 216% compared with the initial heart rate. Systolic blood pressure rose by 5%, whereas there was hardly any change in diastolic blood pressure. As the number of insertion attempts increased, we recorded a continuous ST-segment depression in eight patients with angiographic changes of the coronary artery system. The depression was already significant at the first attempt (p < 0.05). Compared with the initial reading (0.053 mV), the increase was 335% (p < 0.01) after the second attempt (0.231 mV). One patient whose angiographic findings were normal had no ST-segment depression during TEE. In all eight patients with CAD ST-segment depression during TEE was > 0.2 mV. Since none of the patients complained of angina pectoris, the ST-segment depressions satisfied all the criteria of silent myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370191 TI - Amlodipine once a day in stable angina: double-blind crossover comparison with placebo. AB - Although calcium antagonists form a mainstay of therapy in patients with angina pectoris, the currently available agents have significant limitations. Nifedipine, diltiazem, and verapamil are all high-clearance agents with significant hepatic extraction and rapid clearance, leading to limited and short lived bioavailability necessitating frequent daily administration. In contrast, amlodipine, a dihydropyridine calcium antagonist, has a long half-life of 35-50 h (compared with 3 to 4 h elimination half-life of diltiazem, verapamil, and nifedipine). After oral doses, the relative bioavailability of amlodipine is high (64%) and absorption is smooth, with peak plasma levels being achieved 6-12 h postdose. Bioavailability is not affected by the consumption of food. In common with other dihydropyridine calcium antagonists, amlodipine is eliminated mainly by metabolism. None of the metabolites of amlodipine has significant calcium antagonist effects in humans. In contrast to verapamil or diltiazem, amlodipine has no effect on sinus or atrioventricular node and little or no effect on the resting heart rate. Amlodipine does not have any appreciable negative inotropic effect with the relevant clinical dose. Other clinical studies have shown amlodipine to be effective when used once-daily in chronic stable angina and vasospastic angina. Comparative studies indicate that the antianginal efficacy of amlodipine is comparable to the beta blocker nadolol and the benzothiazepine calcium antagonist diltiazem. Amlodipine has also been found to provide improved antianginal effects when combined to treatment with beta blockers and/or long acting nitrates. Treatment with amlodipine either as monotherapy or combined with other antianginal therapy for up to 26 weeks shows that efficacy is maintained, with no evidence of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370192 TI - Interobserver variation in interpretation of electrocardiographic signs of atrial infarction. AB - The electrocardiogram (ECG) is the only means of diagnosing atrial infarction antemortem. Certain ECG changes (PR-segment displacements) have been taken earlier as signs of atrial infarction. The purpose of this study was to assess the interobserver variation on suggested ECG signs of atrial infarction in patients admitted with acute myocardial infarction. The ECGs from 290 patients were evaluated by three physicians with respect to the occurrence of each of the following seven criteria suggestive of atrial infarction: (1) PR-segment elevation > 0.5 mm in lead I; (2) PR-segment depressions > 0.5 mm in leads II and III; (3) PR-segment depressions > 1.2 mm in leads I, II, and III; (4) PR-segment depressions > 0.5 mm in leads V1 and V2; (5) PR-segment elevations > 0.5 mm in leads V5 and V6; (6) PR-segment depressions > 1.5 mm in precordial leads; and (7) abnormal P waves. Kappa values ranged from 0.00-0.86. Of the seven criteria tested only criteria 2, 4, and 7 could be detected in a reasonable number of patients. The interobserver variations of these criteria were considerable, although the strength of agreement could be designated as fair to moderate. PMID- 8370193 TI - Changes in pulmonary hemodynamics predict benefits in exercise capacity after ACE inhibition in patients with mild to moderate congestive heart failure. AB - Several causes may affect the efficacy of angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). The present study was undertaken to identify what factors might predict benefits in exercise capacity after ACE inhibition in 22 patients with mild to moderate CHF. All patients underwent hemodynamic evaluation before and following an oral dose of quinapril (20 mg). They were then treated daily with 20 mg of quinapril and underwent exercise stress test off-drugs 1 day and 6 months later. Patients were grouped according to their relative changes in vascular resistances after quinapril: Group A (n = 15) showed a greater decrease in pulmonary vascular resistance (PVR) than in systemic vascular resistance (SVR) (% delta PVR/% delta SVR > 1). The opposite occurred in Group B (n = 7). Comparison of pretreatment baseline features revealed that the two groups had similar biochemical and hormonal variables, cardiac index, and SVR. Conversely, Group A patients had higher (p < 0.05) pulmonary artery pressure and PVR compared with Group B patients. Following quinapril, Group A patients showed a greater (p < 0.05) increase in cardiac index than Group B patients, despite a similar reduction in SVR. Accordingly, 1-day drug treatment significantly (p < 0.001) increased exercise duration in Group A (+29%), but not in Group B patients (+7%). Benefits in exercise capacity were still significant (p < 0.001) 6 months later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370194 TI - Structural and dynamic changes in the elastic arteries due to arterial hypertension and hypercholesterolemia. AB - Five groups of 20 patients each were studied to analyze the vascular dynamics and structure of the elastic arteries. Group I consisted of healthy young individuals (27 +/- 4 years); Group II of healthy adults (46 +/- 9 years); Group III of normotensive hypercholesterolemic adults (45 +/- 12 years and serum cholesterol > 239 mg/dl); Group IV of hypertensive normocholesterolemic adults (56 +/- 13 years); and Group V of hypertensive hypercholesterolemic adults (56 +/- 9 years). The differential arterial pressure was estimated and divided by the volume change (delta P/delta V) of the aorta and the carotid and brachial arteries. The volume change was calculated using the "cylinder formula", measuring the radius from the ultrasonographic vessel image and assigning the cylinder a height of 1 cm. The A/E index of the Doppler transmitral spectrum and the maximum velocity flow using Doppler in the above arteries were calculated. The presence of carotid atherosclerosis was observed and given an arbitrary scoring grade of 0, 1, or 2. A higher arterial and ventricular stiffness was found in the hypertensive patients regardless of the presence of hypercholesterolemia. A higher fall in Doppler velocity and an increase in atherosclerosis lesions were found in Group V. Based on the results of this study, it was concluded that vascular and left ventricular stiffness have a close relationship with arterial hypertension but not with hypercholesterolemia. The hypercholesterolemic patients had a higher prevalence of carotid atherosclerosis and a higher scoring grade of severity. PMID- 8370195 TI - Ventricular tachycardia due to sustained bundle branch reentry: diagnostic and therapeutic considerations. AB - We have identified bundle-branch reentry (BBR) as the mechanism of ventricular tachycardia (VT) during electrophysiologic studies in 48 patients at our institution. All but three patients had significant structural heart disease, that is, dilated ischemic or idiopathic cardiomyopathy, the most common of anatomic substrates. Syncope and sudden death were the modes of presentation in up to 70% of these patients. The critical prerequisite for the development of this arrhythmia is conduction delay in the His-Purkinje system, which was present in all patients and manifests as a nonspecific conduction delay or a left bundle branch block (LBBB) in the surface electrocardiogram (ECG) and a prolonged HV interval in the intracardiac recordings. VT with an LBBB morphology is the most common form of BBR, present in 98% of patients. Transcatheter ablation of the right bundle branch (RBB) with the use of radiofrequency current is the treatment of choice, as it effectively eliminates BBR. During long-term follow-up, recurrent tachycardia due to BBR was not documented in any patient; however, congestive heart failure was a common cause of death in this population. PMID- 8370196 TI - Anatomy, histology, and pathology of the cardiac conduction system--Part VI. AB - Various pathologic conditions producing atrioventricular block are reviewed. Calcific atrioventricular block (aortic stenosis, mitral valve annular calcium), active infective endocarditis ("ring" abscess), acute and healed myocarditis, various collagen-vascular diseases, amyloidosis, and tumors are reviewed as causes of atrioventricular block. Various diseases producing bundle-branch block are also discussed. PMID- 8370198 TI - [Electrophysiological analysis of diabetic polyneuropathy with microneuronography]. AB - We recorded median nerve action potentials in 40 healthy individuals and 40 patients with type II diabetes mellitus by means of microneurography. The latter group included 20 patients complicated by dysesthesia of distal extremities (mean diabetic history: 12.4 years), and another 20 patients without dysesthesia (mean diabetic history; 5.5 years). Mean age of each group was about 60 years old and had no significant difference among three groups. Patients and healthy controls gave an informed consent for participation in this study. A tungsten microelectrode with a tip diameter of about 1 micron was inserted percutaneously into the median nerve trunk at elbow without anesthesia. With supramaximal electric stimulation on the median nerve at wrist, the largest compound nerve action potential was recorded. In healthy controls the median nerve action potential showed a large triphasic wave (positive-negative-positive, 400 microV in average amplitude) followed by small multiphasic waves. In diabetics maximal conduction velocity (NCV) and amplitude of this triphasic wave (Amp) were decreased and multiphasic waves became more prominent. Reproducibility of potentials in the same subject was acceptable. The differences among three groups were most conspicuous in Amp, and the amplitude of the multiphasic wave was increased in diabetic patients with dysesthesia. Thus, the diminution of Amp appeared to be associated with temporal dispersion due to segmental demyelination. In diabetic polyneuropathy NCV and Amp decreased along with the disease progression; in patients with advanced disease and subjective symptoms, small Amp and prominent multiphasic waves became apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370197 TI - H. Newell Martin. PMID- 8370199 TI - [Event-related potentials in progressive supranuclear palsy]. AB - Abnormal event-related potential (ERP) has been reported in several types of dementing illness including Parkinson's disease (PD) and progressive supranuclear palsy (PSP). In this paper we report the result of EPR recordings obtained in normal control subjects (14 cases) and in patients with PSP (6 cases) and PD (32 cases). ERPs were recorded from 13 scalp electrodes, using the acoustic odd-ball paradigm. All PD patients were in early stage (Yahr stage 1 to 2), and all PSP patients were in the mild-to-moderate state. In control subjects and PD patients P3 was normal. In PSP patients, only one subject (17%) showed a normal P3 component, three cases (50%) demonstrated low amplitude and normal latency P3, and two cases (33%) featured lack of normal P3 sequence. The P3 abnormalities in PSP patients were not related with dementia, but with low amplitude P3 being observed in 2 of 3 non-demented patients, and abolished P3 in a patient with only mild dementia. The result suggests that the P3 changes in PSP patients develop earlier than the cognitive dysfunction, and they are related to the underlying subcortical lesion rather than dementia. PMID- 8370200 TI - [A pathological study of basilar artery sclerosis resulting from vertebral artery asymmetry]. AB - We conducted a pathological study of the arteries of Willis ring in 130 autopsied specimens to evaluate the influence of vertebral artery (VA) asymmetry on basilar artery (BA) sclerosis. The cases studied comprised 109 of non-brainstem infarction (control) and 21 of thrombotic basilar artery occlusion (BAO). The frequency of VA asymmetry was significantly higher (p < 0.01) in BAO cases (13 out of 21 cases; 61.9%) than in the controls (35 out of 109; 32.1%). In the controls, the mean scores for stenosis of the caudal (p < 0.01) BA were significantly higher in VA asymmetry pattern than in VA normal pattern, but the mean score of the rostral BA was nearly equal in both patterns. In BAO cases with VA asymmetry, the score for stenosis was higher in the caudal portion than in the rostral portion, and occlusion was frequently found in the lower BA and continuing from the thicker VA to the BA. These findings suggest that atherosclerotic changes may occur more preferentially in the lower BA in cases of VA asymmetry, and that VA asymmetry is considered to be one of the risk factors for BA occlusion. PMID- 8370201 TI - [A case of migraine with aura associated with meningioma]. AB - We reported a case of migraine with aura associated with meningioma. A 66-year old female visited to our department in 1985, with occipital throbbing pain following visual hallucination and nausea. She had been diagnosed as migraine. CT scan, magnetic resonance image and angiography showed a right occipital tumor, which was totally removed in 1990. Postoperatively, the migraine disappeared completely. The tumor was histologically diagnosed as fibroblastic meningioma. We supposed that the migraine had been associated with meningioma. Although some previous papers reported correlation with brain tumor and migraine, as example of arteriovenous malformation or angioma, migraine associated with meningioma is very rare. In arteriovenous malformation, pathophysiology of migraine is unclear, but induction of circulatory disturbance in the distribution of the posterior cerebral, posterior communicating and basilar artery is supposed. And then a space occupying lesion in the occipital lobe is possible to cause in the circulatory disturbance of the posterior cerebral and basilar artery. In the diagnosis of migraine, we should consider its relation to brain tumors, such as meningioma. PMID- 8370202 TI - [Juvenile Binswanger-type encephalopathy with alopecia and spondylosis deformans- a case report]. AB - The patient is a 33-year-old male and his parents are first cousins. He noticed his hair loss since about the age 14. At age 29, he manifested gait disturbance and urinary incontinence, which gradually progressed. Neurologically, he showed dementia (WAIS < 64), pyramidal and extrapyramidal signs, and pseudobulbar palsy. His blood pressure was normal. He also had dry skin with sclerema and marked cervical and lumbar spondylosis. His brain CT showed enlargement of the lateral ventricles and the periventricular low density areas. T2 weighted image of MRI showed diffuse high intensity in the periventricular white matter. Yamada et al presented a case progressive subcortical vascular encephalopathy (Binswanger type) with alopecia and spondylosis as a possible new syndrome, and this patient has the same syndrome. The etiology of this syndrome has not been known at the present time. The biopsied skin from the patient showed much hyaline deposits like glycoprotein in perivascular area of dermis. These morphological changes are very similar to those of lipoid proteinosis. These findings suggested that the pathological mechanism of this syndrome might be related to the biochemical disturbance in lipoid proteinosis. PMID- 8370203 TI - [A case of non-Fukuyama type congenital muscular dystrophy with progression in early adulthood, ocular involvement, and sensorineural deafness]. AB - Congenital muscular dystrophy (CMD) is a concept applied to infants showing muscular weakness and hypotonia at birth, with myopathic changes which are histopathologically similar to those of muscular dystrophy. Patients with Fukuyama-type CMD (FCMD), characterized by progressive muscular dystrophy, mental retardation and occasionally, convulsions, are more frequently seen in Japan than those with non-Fukuyama type CMD (NFCMD). FCMD has been regarded as a distinct clinical and pathological entity, although the nosologic status of CMD is still controversial. A 24-year-old man had exhibited hypotonia and weakness at birth and delay in early development. During childhood, his muscular weakness improved, and he rode a bicycle and enjoyed skiing. However, his strength began to deteriorate at the age of 19 years. Neurological examination on admission revealed prominent muscular wasting and weakness, predominantly in the proximal limbs. He had ocular involvement (corneal opacity and slow saccades), sensorineural deafness, and a high-arched palate, saddle nose and funnel chest as anomalous conditions. Serum CK was moderately elevated and EMG showed myogenic patterns. A muscle biopsy specimen of the left biceps brachii was dystrophic, showing increased variation in fiber size with fibrous tissue proliferation, an increased number of centralized nuclei, fiber splitting and degenerating/regenerating fibers. Those findings were compatible with those seen in NFCMD. In Japan, only one patient with NFCMD who was followed to adulthood has been reported. This patient's symptoms progressed very slowly. The present patient's course of illness was stable during childhood but progressive in early adulthood. It suggests heterogeneous clinical expression of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370204 TI - [A case of Crow-Fukase syndrome associated with chronic pachymeningitis]. AB - A 34-year-old woman was admitted to our hospital in 1991, because of progressive headache, nausea and generalized edema. She was diagnosed as Crow-Fukase syndrome associated with plasma cell dyscrasia (IgA lambda type) in 1987, presenting with polyneuropathy, edema, and dermatologic changes. Those manifestations were improved with irradiation and corticosteroids, but headache, nausea and generalized edema gradually developed after the discontinuation of corticosteroid therapy in 1991. On admission, marked bilateral papilledema was noted but fever and meningeal irritation signs were absent. A spinal tap showed a clear cerebrospinal fluid (CSF) with an open pressure of more than 400 mmH2O, normal cell count, total protein level of 87 mg/dl, and IgG level of 12.3 mg/dl. The CSF culture for microorganisms was negative and the cytological study of CSF also was normal. De novo synthesis rate of CSF IgG was markedly elevated (35.3 mg/day). MRI of the head using Gd-DTPA revealed diffuse hypertrophic dura mater, which made the diagnosis of chronic pachymeningitis. Cerebral angiographies were normal. An RI cisternography demonstrated delayed absorption of the CSF without ventricular reflux. Gallium and bone scintigrams did not show any pathological accumulation of the isotopes in the head. The lack of abnormalities causing chronic pachymeningitis in this case suggests that the chronic pachymeningitis might be associated with Crow-Fukase syndrome. The development of increased intracranial pressure is not rare in Crow-Fukase syndrome but the etiology remained unknown in most cases. We therefore suggest that MRI study with contrast enhancement should be performed in cases of this condition with increased intracranial pressure. PMID- 8370205 TI - [Superior sagittal sinus thrombosis in paroxysmal nocturnal hemoglobinuria--an autopsied case]. AB - A 43-year-old Japanese man was admitted to our hospital because of acute occipital headache and drowsiness. He had been diagnosed as paroxysmal nocturnal hemoglobinuria (PNH) with acute renal failure for 2 months prior to the admission. He had abdominal pain and fever of unknown origin for 2 weeks. On admission neurological examination revealed mild disturbance of consciousness, right papilledema and minimal nuchal rigidity. The urinalysis was normal and blood hemoglobin was 8.3 g/dl. Mild hemolysis was suspected because of decreased level of the serum haptoglobin. The magnetic resonance imaging (MRI) of the brain demonstrated the complete occlusion of the superior sagittal sinus by fresh thrombus and the cerebral hemorrhage in the right parieto-occipital subcortex. No other cause for cerebral sinus thrombosis was detected. The patient was treated medically using anti-edema agents, but on the twentieth hospital day he died because of brain herniation. The postmortem examination disclosed thrombosis in the superior sagittal sinus and transverse sinus on both side. There was a massive hematoma in the right parieto-occipital subcortex. The spleen and kidney also contained multiple venous thromboses. Twelve cases of cerebral sinus thrombosis with PNH have been reported in the literatures. Although cerebral sinus thrombosis is a common complication with PNH in Caucasian, but is rare in Asian including Japanese. This may probably depend upon a racial difference. To our knowledge, this is the first report of a patient with cerebral sinus thrombosis with PNH in Japan. PMID- 8370206 TI - [Isolated inferior rectus muscle paresis from midbrain infarction]. AB - A 74-year-old woman, with hypertension and dilated cardiomyopathy, presented with sudden onset of diplopia without vertigo and other neurological symptom. Examination revealed left inferior rectus muscle paresis. Other neurological findings were normal. She had no cerebellar ataxia and sensori-motor dysfunction. Magnetic resonance imaging showed increased signal intensity on T2-weighted and proton density-weighted images in the right ventral midbrain, compatible with infarction involving the fascicular oculomotor fibers. Complete resolution of the diplopia and normal ocular motility were noted 3 months after the onset of the diplopia. Focal ischemic midbrain lesions should be considered in cases of isolated partial oculomotor nerve paresis. PMID- 8370207 TI - [A case of facial nerve neurinoma originated from cerebellopontine angle]. AB - A 77-year-old man who had been diagnosed as the right peripheral facial palsy ten years ago, slowly developed progressive hearing loss and gait disturbance. He died of pneumonia. The autopsy revealed a tumor (4.7 x 2.6 x 2.6 cm) arising from the facial nerve in the region of the right cerebellopontine (C-P) angle. The tumor was displacing the cochlear and vestibular nerve, but did not extend laterally into the internal auditory meatus. Histological diagnosis of this tumor was neurinoma. Facial nerve neurinomas are relatively rare and most of them appear at the vertical portion of the facial nerve. Facial nerve neurinoma originated from the C-P angle is less frequently reported. The most frequent symptom of this neurinoma is hearing loss. We emphasize that preoperative diagnosis of facial nerve neurinoma in the C-P angle is difficult from neurological symptoms, even with CT scanning. PMID- 8370208 TI - [A case of multiple sclerosis manifesting piano playing movement]. AB - We report a case of 33-year-old man with multiple sclerosis, showing piano playing movement in both hands. His course of multiple sclerosis was remittent/progressive during 2 years and the clinical manifestation suggested the spinal cord involvement. On July 15, 1991, he was admitted with numbness of the right limbs, and then developed piano playing movement in both hands, more marked in the right side. Neurological examination revealed mild weakness in the right upper extremity, and rough touch, pain, and temperature sensation were slightly decreased. However, there was no deep sensory abnormalities, such as vibration, fine touch, and position senses. Vibration sense was lost below ilium. CSF examination showed elevation of IgG index (1.6), three oligoclonal bands and myelin basic protein content of 2.4 ng/ml. There was no HTLV-I antibody in CSF. SSEP, elicited by median nerve stimulation at the right wrist, showed no N13 and low amplitude of N20. T2-weighted images of cervical MRI revealed area of high signal intensity at the C3-C4 level. The piano playing movement gradually improved and disappeared by the initiation of steroid hormone therapy. It was considered that involuntary movement in this patient was due to the spinal cord lesion caused by multiple sclerosis. These findings suggested that the involuntary movement like pseudoathetosis could present without deep sensory abnormalities. PMID- 8370209 TI - [Diffusion weighted magnetic resonance imaging in multiple cerebral infarction]. AB - Serial examination of magnetic resonance images (MRI) for two months were carried out on two cases of multiple cerebral infarction during the acute stage. The T2 weighted MR images at the onset of the infarction showed both acute (new) and chronic (old) lesions appearing as high signal area. While on the diffusion weighted images only an acute lesion was detected as a high signal area with good contrast. The diffusion coefficient of the acute lesion was lower than that of normal white matter. Diffusion coefficient of the chronic lesions were higher than that of normal white matter. Therefore, on the apparent diffusion coefficient mapping images (ADC images) only an acute lesion appeared as a low signal area. The examination of diffusion images was very useful for distinguishing an acute lesion from a chronic lesion during the acute stage of multiple infarction. The diffusion weighted images after 4 weeks from the onset showed the diffusion coefficient of the "acute" lesion to be the same level of normal white matter. And after 8 weeks from the onset, increased to a level higher than that of normal white matter to the same level of the "chronic" lesion. PMID- 8370210 TI - [Lesion of the bilateral MLF and unilateral paramedian pontine reticular formation, caused by an infarction in the midbrain tegmentum]. AB - A 71-year-old man with bilateral medial longitudinal fasciculus (MLF) syndrome and paralytic pontine exotropia caused by an infarction of the midbrain tegmentum was reported. He suddenly noticed a diplopia and gait disturbance, and visited our clinic. Neurological examination revealed that this right eye was slightly abducted in the primary position. On horizontal gaze, outwardbeating nystagmus of the abducted eyes was observed, bilaterally. The adduction of the bilateral eyes was severely disturbed and the abduction of the left eye was slightly restricted, while the convergence was normal. T2-weighted magnetic resonance imaging revealed high signal intensity area in the medial portion of the midbrain tegmentum, which indicated an infarction. Several cases showing bilateral MLF syndrome with exotropia have been reported, but a case whose lesion was shown in the midbrain has not been reported so far. The present case suggests that paramedian pontine reticular formation (PPRF) is not confined to pons but expands to midbrain. PMID- 8370211 TI - [An immunopathological study during steroid-responsive and steroid-nonresponsive stages on a patient with neuro-Behcet's disease]. AB - We followed up the clinical course and changes of brain magnetic resonance imaging (MRI) findings in a case of neuro-Behcet's disease, and performed serial immunological examinations of the cerebrospinal fluid (CSF). On the two episodes of acute exacerbation, gadolinium (Gd)-enhancement effects on brain MRIs were observed in the brain stem and the deep white matter of cerebral hemispheres. The CSF abnormality of this period was characterized by increases in proportions of polymorphonuclear leukocytes and intrathecal IgG synthesis in addition to the findings suggesting breakdown of the blood brain barrier (BBB). These findings disappeared in parallel with clinical improvement by corticosteroid therapy. In contrast, during a subsequent chronic progressive stage, steroid-resistant neuropsychiatric symptoms and an absence of Gd-enhancement effects on brain MRIs were observed despite progressive breakdown of BBB. These findings suggest that neuro-Behcet's disease should comprise two distinct immunopathogenetic stages, that is, a relatively early steroid-responsive stage with a relapsing-remitting clinical course and a late steroid-nonresponsive stage with a chronic progressive course. PMID- 8370212 TI - [Cerebrospinal fluid and plasma corticotropin-releasing hormone (CRH) in dentatorubropallidoluysian atrophy (DRPLA)--study in two cases of hereditary DRPLA]. AB - The levels of corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) and plasma were examined in two cases of hereditary dentatorubropallidoluysian atrophy (DRPLA). Both patients were female and showed cerebellar ataxia, choreic movement and subcortical dementia. The onset ages of the first and second patients were 30 and 47 years, respectively. The first patient did not have the cerebral white matter damage (CWD). The second patient of late onset was associated with marked and diffuse CWD which was shown as high signal intensity by T2-weighted image on MRI. Regardless of accompaniment with CWD, the radioimmunoassay studies of CSF and plasma CRH revealed that both patients had markedly reduced levels of CRH in CSF and plasma. Together with the recent anatomic evidence on the distribution of CRH neurons and receptors in the central nervous system, the present results suggest that degeneration of the subcortical structures including the basal nuclei, the brain stem and the cerebellum involves degeneration and/or dysfunction of the CRH neuronal system which, presumably, are related to those of some other neurotransmitter systems, and that the reduced activity of the CRH system plays a pathophysiological role in such diseases as DRPLA with degeneration of the subcortical nuclei and the cerebellum. PMID- 8370213 TI - [Fungal meningitis caused by a Malassezia species masquerading as painful ophthalmoplegia]. AB - The patient, an otherwise healthy 42-year-old woman, developed non-throbbing periorbital pain and abducens nerve palsy of the right side two weeks prior to the present admission. Under the diagnosis of Tolosa-Hunt syndrome, she had been placed on prednisolone (30 mg/day) in another hospital, leading to exacerbation of her neurologic manifestations. On admission, neurologic examination revealed bilateral abducens nerve palsy, incomplete bilateral oculomotor paresis, and hypalgesia in the first and the second branch of the left trigeminal nerve. On CSF examination there were 742/mm3 white blood cells of which about 80% of the cells were neutrophils. The glucose was 70 mg/dl (blood glucose was 170 mg/dl) and the protein 49 mg/dl. Although repeated cultures for bacteria or fungi were negative, PAS stains for CSF sediments showed a large number of yeasts morphologically consistent with a Malassezia species. Anti-fungal treatment with fluconazole and flucytosine resulted in dramatic improvement both in neurologic signs and laboratory findings. According to morphological criteria, the yeasts found in CSF sediments from this patient differed from those described previously as being pathogenetic in the CNS fungal infection. By contrast, these yeasts were similar to a Malassezia species in all aspects. Because some Malassezia requires oil for its growth in culture, it is possible that it failed to grow in the standard media and thus escaped recognition. PMID- 8370214 TI - Colour flow and spectral Doppler imaging after papaverine-induced penile erection in 220 impotent men: study of temporal patterns and the importance of repeated sampling, velocity asymmetry and vascular anomalies. AB - Of 220 impotent men studied, 52 demonstrated venous leakage, 85 had arterial insufficiency and 65 showed normal vascular response. Persistent diastolic velocity > 7 cm/s diagnosed venous leakage with a sensitivity of 94% and a specificity of 69%, using cavernosography as the reference standard. Using clinical response as the reference standard maximal systolic velocity of 30 cm/s identified normal penile arterial response with a sensitivity of 96% and specificity of 82%. There was a good correlation between penile arterial insufficiency and a strong history of arteriopathy. Time to peak systole > 0.1 s was a reliable predictor of arteriogenic impotence and Pulsatility Index (PI) < 300 was discovered only in patients with either venous leakage or arteriogenic impotence. Peak systolic velocity (Tmax) occurred between 5.2 and 6.5 min after injection, and diastolic velocity was minimal at 9 min with only the normal responders showing reversed diastolic flow. However, 22% had a delayed response (Tmax range 1-18 min). Velocity asymmetry was equally common in the three groups and unilateral sampling would have misdiagnosed 6% of patients studied. Vascular anomalies were seen in 13%, particularly a single feeding artery, dorsal vein flow or collateral arterial flow. PMID- 8370215 TI - The effective use of magnetic resonance imaging in the diagnosis of acoustic neuromas. AB - The diagnostic approach to acoustic neuromas is complex but these tumours are infrequent in patients even with a suggestive clinical picture. Easy access to an efficient, reliable and cost effective investigation is desirable. Magnetic resonance imaging is now the imaging modality of choice and this paper shows that it may be used effectively as the sole investigation. T2-weighted (T2W) fast spin echo axial images taking 1 min 37 s to acquire were compared with T1-weighted (T1W) gadolinium-enhanced axial images, taking 5 min 11 s to acquire, in 157 patients. The T2W images were satisfactory alone in 43% of patients and allowed confident diagnosis of seven of the nine acoustic neuromas. Partial volume artefact and CSF flow artefact resulted in equivocal examinations in the remaining patients. Using both sequences in every patient, imaging time was 7 min 41 s and at least 40 patients could be examined in 1 day, thus ensuring efficient patient throughput. We suggest that T2W fast spin echo axial images be routinely obtained and that only when they are equivocal should T1W gadolinium-enhanced axial sequences be employed. PMID- 8370216 TI - Aortoarteritis of abdominal aorta: an angiographic profile in 110 patients. AB - The angiographic appearances in 110 patients (49 males, 61 females, age range 11 46 years, mean 27.8 years) with aortoarteritis involving the abdominal aorta and/or its branches were analysed. There were 41 aneurysms of the abdominal aorta in 37 patients and eight aneurysms of its branches in as many patients. In 50 patients, 53 obstructive lesions involved the abdominal aorta and were classified as stenoses of focal, segmental and diffuse types and total occlusions. Branch obstructions (182 lesions in 85 patients) affected in order of frequency, the renal, superior mesenteric, coeliac, iliac and the inferior mesenteric arteries. Mesenteric arterial lesions were significantly more common in males (P = 0.01). Collateral circulation through a prominent mesenteric arcade was a distinctive angiographic feature in 28 patients. Computed tomography done in four patients showed peri-adventitial thickening and layered thrombus within aneurysms in three patients, and luminal occlusion of the upper abdominal aorta in one patient. Angiographic appearances in aortoarteritis of the abdominal aorta are characteristic and sufficiently distinctive for definitive diagnosis and appropriate management. PMID- 8370217 TI - A long term follow-up of Gunther vena caval filters. AB - Seven patients with Gunther inferior vena caval filters were reviewed between 28 and 60 months following insertion of the filter. Some 71% of the filters showed some sort of structural failure, the commonest of these being limb fracture (57%). Fifty-seven per cent also showed either fracture or severe distortion of the basket. Twenty-nine per cent of the filters had suffered loss of an anchoring limb. Only one patient had any clinical sequelae, this being an IVC occlusion. This study confirms that Gunther inferior vena caval filters have a structural failure rate of greater than 50%. PMID- 8370218 TI - Mammographic parenchymal patterns in Asian and Caucasian women attending for screening. AB - The breast parenchymal patterns were assessed and compared on the screening mammograms of 200 Asian and 400 Caucasian women, matched for age and between 50 and 64 years of age. The breast patterns were allocated according to Wolfe's classification. The results show a significant excess of Asians in the P1 and N1 groups and a deficit in the P2 group. Taking N1 and P1 as a low risk group and P2 and DY as a high risk group, there is a highly significant excess of Asians in the low risk group. These findings are considered in relation to the low incidence of breast cancer in Asian women and their poor acceptance of breast screening. PMID- 8370219 TI - Ultrasound in the diagnosis of gall-bladder carcinoma in Chinese patients. AB - A review of the ultrasound (US) findings with clinical and pathological correlation in 18 Chinese patients with gall-bladder carcinoma (GBCa) showed that the most frequent appearance was that of diffuse infiltration and thickening of the GB wall (8/18 patients, 44%). Polypoid protrusion into the GB lumen (5/18 patients, 28%) and massive replacement of the entire GB (5/18 patients, 28%) accounted for the remainder. The infiltrating type of tumour was poorly-detected by US (1/8) and was more frequently seen than has been reported in the Western population. Frequent associations with GB calculi (13/18) and synchronous presentation of biliary sepsis (6/18) also contributed to a modest overall US detection rate of 50% (9/18) in this series. Most tumours detected by US were hyperechoic in appearance (6/9). Biliary obstruction was detected by US in 5/6 patients, but only thought to be malignant in 3/6. It most often occurred due to spread of tumour to peripancreatic lymph nodes. Hepatic metastases were seen by US in 4/5 patients. Discontinuous GB wall calcification and non-dependent stones due to elevation by tumour (the 'elevated stone' sign) were infrequent but reliable signs of GBCa, seen in 5/18 and 3/18 respectively. This study suggests that GBCa is as difficult to detect sonographically in Chinese patients as in the Western population. GBCa must be included in the differential diagnosis of causes of both the acutely-presenting 'hot' gall-bladder and lymph node masses in the peripancreatic region if the US detection rate of this important biliary malignancy is to be improved. PMID- 8370220 TI - Barium enema or computed tomography for the frail elderly patient? AB - In order to determine whether abdominopelvic computed tomography (CT) offers an alternative to barium enema (BE) for the investigation of the large bowel in frail elderly patients, we have assessed and compared the results of both tests performed in each patient. Thirty-seven patients aged 71 to 88 (mean 80) with a history or clinical findings suggestive of large bowel disease were studied. The seven colonic neoplasms in this group were demonstrated by both techniques (apart from one patient who did not undergo BE as CT had shown an obstructing lesion). CT showed useful additional data in four patients (e.g. abdominal wall involvement) and demonstrated numerous extracolonic lesions (e.g. ovarian carcinoma). However, CT did raise the possibility of a large bowel neoplasm in four patients where none was shown by BE and missed one case of Crohn's disease. CT was the preferred test amongst the 25 patients where the acceptability of the two techniques could be compared. Only in 16 patients were the BE studies adjudged to be of good quality. CT should be the initial investigation of the large bowel in frail elderly patients requiring inpatient bowel preparation; the more unpleasant BE could be reserved for those cases where CT is equivocal or severe symptoms are unexplained. PMID- 8370221 TI - Postaortic left innominate vein: radiological assessment and pathogenesis. AB - Postaortic left innominate vein (PALIV) is a rare venous anomaly and the findings on plain chest radiographs have not been well described. Plain chest radiographs, CT and MR of nine adults known to have PALIV were reviewed. They all showed a high aortic arch, including four with a right-sided aortic arch and one with a double aortic arch, in postero-anterior radiographs, and seven showed curved shadows in the left upper mediastinum. On all lateral chest radiographs (n = 5), the superior retrosternal region was opacified by the high aortic arch. CT or MR images confirmed the aortic arch and/or innominate artery to be in that part of the retrosternal space, normally occupied by the left innominate vein, in all cases. Association of a curved shadow in the superior mediastinum with a high aortic arch on plain chest radiographs is therefore suggestive of, though not diagnostic for, PALIV. This entity was well documented by CT or MR and the radiological findings were considered to imply that developmentally PALIV is secondary to a high position of the aortic arch. PMID- 8370222 TI - Pictorial review: benign and malignant enlargement of the pterygo-masseteric muscle complex. AB - Seven cases of unilateral enlargement of the pterygoid and/or masseter muscles due to haemangioma (1), benign masseteric hypertrophy (2), rhabdomyosarcoma (2), leukaemic infiltration (1) and non-Hodgkin's lymphoma (1) are presented. The differential diagnosis of pterygo-masseteric muscle enlargement is outlined and the usefulness of computed tomography (CT) discussed. PMID- 8370223 TI - Case report: mediastinal lymphadenopathy in eosinophilic pneumonia. AB - Chronic eosinophilic pneumonia is a relatively rare disorder characterized radiologically by non-segmental homogenous consolidation in the lung periphery [1]. We present a patient who had marked mediastinal lymphadenopathy as well as the more typical radiological features, which resolved rapidly with treatment. PMID- 8370224 TI - Case report: computed tomographic and scintigraphic appearances of dermatofibrosarcoma protuberans. AB - The computed tomographic and scintigraphic appearances of dermatofibrosarcoma protuberans involving the mental region are presented. The tumour was demonstrated as a moderately well-defined vascular mass extending from the skin to invade the subcutaneous tissue and strap muscles. Only one case of the imaging features of this rare tumour has been reported previously. PMID- 8370225 TI - Case report: calcification in benign cystic peritoneal mesothelioma. AB - Benign cystic mesothelioma of the peritoneum is a rare multicystic tumour that occurs predominantly in middle aged women with strong predilection for the surface of the pelvic viscera. Our patient was a 79-year-old woman who presented with weight loss and left upper abdominal mass showing calcification on CT. This is the first reported case of benign cystic mesothelioma with calcification. Differentiation from an adrenal tumour and peritoneal teratoma was not possible preoperatively. PMID- 8370226 TI - Case report: generalized arthralgia following Gd-DTPA administration. AB - A case of transient generalized arthralgia in a young female patient following the intravenous administration of Gd-DTPA (dimeglumine gadopentetate-Schering) is presented. We believe that this is the first report of an adverse drug reaction of this nature. PMID- 8370227 TI - Accessory navicular bone. PMID- 8370228 TI - Staging prostatic cancer. PMID- 8370229 TI - Clinico-radiological meetings. PMID- 8370231 TI - Re-engineering health care. PMID- 8370230 TI - Optimum dosage of hyoscine-N-butylbromide for biphasic barium meals. PMID- 8370232 TI - Understanding health care integration. 1. AB - The decade of the 1990s is likely to be looked upon by future social historians and health policy analysts as the time of greatest change in the American healthcare industry. They will point to this decade as the time when new principles of healthcare delivery were implemented. PMID- 8370233 TI - Middle cerebral artery velocity during head-up tilt induced hypovolaemic shock in humans. AB - Middle cerebral artery mean velocity (Vmean) and pulsatility index (PI) were followed during head-up tilt induced hypovolaemic shock in nine subjects. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP) and thoracic (TI) electrical impedance were also recorded. Vmean, PI, and CVP did not change during head-up tilt to 50 degrees, while MAP increased from 92 (81-106) (median and range) to 100 (97-112) mmHg, HR from 63 (53-74) to 84 (68-89) beats min-1 and TI100kHz from 30 (27-36) to 32 (30-39) Ohm (P < 0.01) (n = 8). During maintained tilt, Vmean decreased from 52 (32-72) to 34 (16-59) cm s-1, whereas HR increased to 87 (52-108) beats min-1 and TI100 kHz to 33 (31-39) Ohm (P < 0.01). Presyncopal symptoms appeared after 33 (3-46) min and were associated with a MAP of 65 (32-84) mmHg (P < 0.01) and a HR of 58 (52-71) beats min-1 (P < 0.05). Vmean decreased to 25 (16-36) cm s-1, and cerebral conductance index (Vmean/MAPbrain) and PI increased (P < 0.01). Arterial collapse was observed (diastolic velocity of zero) in one subject at a brain (diastolic) blood pressure of 21 mmHg and he developed tachycardia (131 beats min-1) during presyncope. PaCO2 did not change. Maintained tilt resulted in central volume depletion reflected by changes in MAP, HR, and thoracic electrical impedance but not in CVP. Transcranial Doppler derived indices of cerebral perfusion demonstrated critically low values despite marked increase in conductance index. PMID- 8370234 TI - Work capacity and metabolic and morphologic characteristics of the human quadriceps muscle in response to unloading. AB - The response of skeletal muscle to unweighting was studied in six healthy males who were subjected to four weeks of lowerlimb suspension. They performed three bouts of 30 consecutive maximal concentric knee extensions, before unloading and the day after (POST 1), 4 days after (POST 2) and 7 weeks after (REC) resumed weight-bearing. Peak torque of each contraction was recorded and work was calculated as the mean of the average peak torque for the three bouts and fatigability was measured as the decline in average peak torque over bouts. Needle biopsies were obtained from m. vastus lateralis of each limb before and at POST 1. Muscle fibre type composition and area, capillarity and the enzyme activities of citrate synthase (CS) and phosphofructokinase (PFK) were subsequently analysed. Mean average peak torque for the three bouts at POST1, POST2 and REC was reduced (P < 0.05) by 17, 13 and 7%, respectively. Fatigability was greater (P < 0.05) at POST2 than before unloading. Type I, IIA and IIB percentage, Type I and II area and capillaries per fibre of Type I and II did not change (P > 0.05) in response to unloading. The activity of CS, but not PFK, decreased (P < 0.05) after unloading. The weight-bearing limb showed no changes in the variables measured. The results of this study suggest that this human lowerlimb suspension model produces substantial impairments of work and oxidative capacity of skeletal muscle. The performance decrements are most likely induced by lack of weight-bearing. PMID- 8370235 TI - The effect of opioids on inspiratory muscle fatigue during inspiratory resistive loading. AB - The effect of opioids on inspiratory muscle function under high mechanical load is still unknown. Even less clear is the extent to which opioids influence the shift of the electromyographic power spectrum of the inspiratory muscles to lower frequencies during ventilatory stress. We studied seven healthy subjects breathing against high inspiratory threshold loads until exhaustion while keeping the minute ventilation constantly high. We compared runs with and without administration of 0.2 mg kg-1 of morphine sulphate intramuscularly; two subjects were given 30 mg morphine sulphate so that we could study the effect of higher opioid concentration. The endurance time (Tlim), the diaphragmatic electromyogram (EMG), the transdiaphragmatic pressures (Pdi) and the ventilatory effort sensation were analysed. Morphine did not have any effect on Tlim or on the effort sensation elicited by the inspiratory resistance in both concentrations. Analysing the spectral shifts of the diaphragmatic EMG, we did not find any significant difference in the decrease of the centroid frequency between drug and control runs. Furthermore, the activation pattern of the diaphragm and the intercostal muscles, evaluated from the percentage contribution of oesophageal and gastric pressures on the transdiaphragmatic pressure swings, did not change following the administration of morphine. Our study shows that morphine does not change the function of the inspiratory muscles during high-resistive breathing. Morphine does not affect the electromyographic power spectrum of the diaphragm during those resistive breathing runs, either. This points out that during stressful ventilatory situations, the shift of the electromyographic power spectrum is attributed to a peripheral (muscular) event consequent to muscle fatigue and not to the elaboration of endogenous opioids. PMID- 8370236 TI - Renal effects of i.v. adenosine infusion in humans. AB - The effects of systemic intravenous (i.v.) infusion of adenosine on renal blood flow and glomerular filtration in eight healthy, awake females have been examined. Renal blood flow and glomerular filtration rate were measured as the clearance of para-aminohippuric acid (PAH) and inulin, respectively. Following basal sampling adenosine was infused i.v. at successive rates of 60 and 80 micrograms kg-1 min-1 for 30 min at each rate. Plasma clearance of PAH showed a minor, but non-significant, increase from 697 +/- 41 to 775 +/- 97 ml min-1. However, the arterial plasma concentration of PAH decreased by 17 +/- 4% (P < 0.001), indicating that there was a small increase in renal blood flow. Inulin clearance was reduced from 123 +/- 14 to 88 +/- 11 ml min-1 1.73 m-2 (P < 0.01). The resulting filtration fraction was reduced from 18 +/- 1 to 11 +/- 1 (P < 0.001). The K+/Na+ excretion ratio increased from a basal value of 10 +/- 1 to 42 +/- 11 (P < 0.01) at the highest dose of adenosine, and renal oxygen consumption decreased from 17 +/- 2 to 9 +/- 1 ml min-1 (P < 0.001). In conclusion, i.v. infusion of adenosine in healthy, awake subjects causes a minor increase in total renal blood flow and a marked reduction in glomerular filtration. This shows that adenosine also exerts a vasodilatory effect in the renal circulation, primarily on postglomerular arterioles. In addition, adenosine may produce an aldosterone like effect on salt excretion, and a reduction in renal oxygen consumption. PMID- 8370237 TI - Variability of digitized left ventricular M-mode echocardiography: a study in healthy subjects and patients with repaired tetralogy of Fallot. AB - To assess possible factors affecting the variability of digitized left ventricular M-mode echocardiograms, the influence of respiration and the variability due to different beats and observers were analysed in 11 healthy subjects and 11 patients with repaired tetralogy of Fallot. Left ventricular end diastolic dimension (LVEDD) decreased from end-expiration to end-inspiration in the healthy subjects, but not in the patients. The maximal rate of dimension change decreased in both healthy subjects and patients from end-expiration to end inspiration. The beat-to-beat variability assessed by the coefficient of variation (CV,%) between measurements of one cardiac cycle was twice the CV for three cycles, whereas the CV for three and five cardiac cycles was not different. The CV for intraobserver variability was less than 5.0% for dimensions and less than 13.0% for the rates of dimension change, whereas the interobserver variability had CV of 17.1% for rates of dimension changes. The influence of respiration and different observers on the variability of LV end-systolic dimension and shortening fraction was larger in the patients than in the healthy subjects. Thus, to obtain optimal technique for analysis of digitized LV M-mode echocardiograms in serial patient studies, the number of observers should be kept at a minimum and at least 3 beats at end-expiration should be used. PMID- 8370238 TI - Planar 201Tl scintigraphy in ischaemic heart disease: a critical re-evaluation of qualitative and quantitative data analysis. AB - The aims of the present study were to examine the observer agreement of qualitative (visual) and quantitative (computer-assisted) analysis of planar 201Tl imaging and to compare the diagnostic values of these methods in the detection of infarcted and exercise-induced ischaemic myocardium. The study population comprised of 119 patients (aged 24-77 years) referred consecutively for stress thallium scintigraphy for either diagnostic reasons (n = 42, 35%) or for further evaluation of known coronary artery disease (CAD) (n = 77, 65%). The interobserver agreement was low with the qualitative method and significantly higher with the quantitative method: Kappa-values 0.29-0.39 vs. 0.80-0.92, P < 0.00001. Sensitivity and specificity for the detection of previous Q-wave infarct was significantly higher with the quantitative method (94% and 94%) compared to the qualitative method (77% and 74%), P < 0.01. The corresponding predictive values of a positive and a negative test were 96% and 92% vs. 80% and 70% (P < 0.01). In 86 patients in whom coronary angiography was performed the two methods did not differ significantly regarding sensitivity, specificity and predictive values for the diagnosis of reversible ischaemia or rather CAD. However, when 22 patients with a maximal exercise heart rate < 80% of the predicted target heart rate were excluded the sensitivity was increased with both techniques and was significantly higher with the quantitative method. We conclude that qualitative image analysis has an unacceptably low reproducibility and that quantitative image analysis increases the diagnostic value of 201Tl scintigraphy considerably in both the detection of previous infarcts and, provided a sufficient exercise level is achieved, in the disclosure of reversible myocardial ischaemia. PMID- 8370239 TI - Neuropeptide Y, noradrenaline and invasive haemodynamic data in mild to moderate chronic congestive heart failure. AB - Neuropeptide Y (NPY) is a peptide released together with noradrenaline (NA) from sympathetic nerve endings. Elevated plasma levels of NA and NPY-like immunoreactivity (LI) are found in patients with congestive heart failure. In order to assess any relationship found between plasma NPY-LI and haemodynamic data 12 patients with mild to moderate chronic congestive heart failure were studied during cardiac catheterization. All patients were treated with diuretics but not ACE inhibitors and were in New York Heart Association functional class II or III. Mean left ventricular ejection fraction determined by echocardiography was 34%. Plasma NPY-LI from mixed venous blood was elevated in five patients and NA in nine. Mean plasma NPY-LI was 29 +/- 3 pmoll-1 (mean +/- standard error of the mean) and NA 2.6 +/- 0.3 nmoll-1. Heart rate was 70 +/- 3 beats min-1, systolic blood pressure (SBP) 131 +/- 7 mmHg, stroke volume index (SVI) 29 +/- 1.9 ml m-2 and cardiac index (CI) 2.0 +/- 0.13 l min-1 m-2. Elevated levels of plasma NPY-LI (> 30 pmol l-1) were associated with lower SVI, CI, and SBP and a higher pulmonary vascular resistance. Elevated plasma NA (> 2 nmol l-1) did not correlate with haemodynamic data. Log NPY-LI correlated inversely with SVI (P < 0.01) and CI (P < 0.05) but not with plasma NA. It is concluded that log NPY-LI in mixed venous blood correlates inversely with SVI and CI in patients with mild to moderate chronic congestive heart failure. PMID- 8370240 TI - Comparison between reference values for 201thallium uptake and washout from the myocardium after exercise and after dipyridamole. AB - A slow washout of 201Thallium has a high diagnostic and prognostic value for coronary artery disease. The aim of the present work was to contribute with reference data on 201Tl uptake and washout from the myocardium. With a quantitative method using circumferential profiles and interpolative background subtraction we performed 201Tl myocardial imaging in two groups of subjects with a low probability of coronary artery disease. Washout in per cent is defined as (1-D/I).100, where D is the delayed uptake rate and I the initial uptake rate. In group A (n = 16) myocardial hyperaemia was induced by maximal exercise, in group B (n = 15) by intravenous infusion of dipyridamole. In group A, the mean washout was 52%, and in group B it was 34% (P < 0.001). The delayed uptake rate D was significantly higher after dipyridamole, 58.4 cps, than after exercise, 44.5 cps (P < 0.05). There was no significant differences in I between the two groups. The findings regarding D and I explain that the washout is slower after dipyridamole than after exercise, as the mean D/I ratio was 0.48 in group A and 0.66 in group B (P < 0.001). PMID- 8370241 TI - Changes in plasma volume and baroreflex function following resistance exercise. AB - The dynamics of change in plasma volume (PV) and baroreflex responses have been reported over 24 h immediately following maximal cycle exercise. The purpose of this study was to determine if PV and baroreflex showed similar changes for 24 h after resistance exercise. Eight men were studied on 2 test days, 1 week apart. On 1 day, per cent change (% delta) in PV was estimated at 0,3, and 6 h after resistance exercise using haematocrit and haemoglobin. Baseline PV was measured 24 h after exercise using Evans blue dye. The carotid baroreceptor-cardiac reflex response was measured before, and 3, 6, 9, 12, and 24 h post-exercise. Each subject performed six sets of the bench press and leg press with 10 repetitions per set with a load that induced failure within each set. On a control day, the protocol was used without exercise. Plasma volume did not change during the control day. There was a 20% decrease in PV immediately post-exercise; the recovery of the PV was rapid and complete within 3 h. PV was 20% greater 24 h post-exercise than on the control day. There were no differences in any of the baroreflex measurements. Therefore, it is suggested that PV shifts may occur without altering baroreflex sensitivity. PMID- 8370242 TI - The stuff that dreams aren't made of: why wake-state and dream-state sensory experiences differ. AB - It is adaptive for individuals to be continuously alert and responsive to external stimuli (such as the sound and odor of an approaching predator or the cry of an infant), even during sleep. Natural selection thus has disfavored the occurrence during sleep of hallucinations that compromise external vigilance. In the great majority of mammalian species, including Homo sapiens, closed eyes and immobility are basic aspects of sleep. Therefore, (a) visual and movement sensory modalities (except kinesthesis) do not provide the sleeper with accurate information about the external environment or the sleeper's relationship to that environment; (b) the sleeper's forebrain "vigilance mechanism" does not monitor these modalities; hence (c) visual and movement hallucinations--similar or identical to percepts--can occur during sleep without compromising vigilance. In contrast, the other sensory modalities do provide the sleeper with a continuous flow of information about the external environment or the sleeper's relationship to that environment, and these modalities are monitored by the vigilance mechanism. Hallucinations of kinesthesis, pain, touch, warmth, cold, odor, and sound thus would compromise vigilance, and their occurrence during sleep has been disfavored by natural selection. This vigilance hypothesis generates novel predictions about dream phenomenology and REM-state neurophysiology and has implications for the general study of imagery. PMID- 8370243 TI - Processing discontinuous words: on the interface between lexical and syntactic processing. AB - How are discontinuous words processed? Are they identified in the lexicon or in the syntax? Schreuder (1990) proposes the existence of morphological integration nodes (MI nodes) to account for the representation of complex verbs with separable prefixes in Dutch. We tested the MI model during sentence processing in Dutch, using an ungrammaticality judgment task. The results supported the predictions of the Schreuder model, and also provide evidence for distinct lexical/morphological and syntactic processing subsystems, each driven by the information resources and tasks relevant to its own representational vocabulary. It is argued that no special principles are needed to govern the interaction of lexical/morphological and syntactic processing, even for the identification of discontinuous words; this follows automatically from independently required characterizations of the subsystems themselves. We also examine the principles underlying the MI model in an attempt to extend the model to a wider array of constructions and languages. It is hypothesized that frequently encountered linguistic expressions are represented in the lexicon. In the basic case, they are represented as access nodes, if they may stand alone, and as MI nodes, if their constituents are already represented by access nodes. Unlike the original MI model, no further stipulation is needed concerning the existence or inhibition properties of MI nodes, assuming that candidate lexical/morphological hypotheses are appended to whatever portion(s) of the input string they are hypotheses about. PMID- 8370245 TI - Physical fitness. PMID- 8370246 TI - Diagnosis and management of vascular disease in systemic sclerosis. AB - Vascular disease is seen in virtually all patients with systemic sclerosis and presents several challenges to physicians caring for them. Early recognition of isolated pulmonary hypertension and scleroderma renal crisis may be keys to successful outcomes. Although complete reversal of vascular disease is usually not possible, the availability of calcium channel blocking agents for RP and isolated pulmonary hypertension and ACE inhibitors for hypertensive renal disease has improved the morbidity and mortality of these patients. Optimal management of the vascular events in systemic sclerosis will ultimately depend on a clearer understanding of their pathogenesis. Treatment may ultimately be directed at preventing the development of these vascular syndromes. This may occur through combined therapy directed at both the abnormal immune response and disregulated fibroblast function seen in the disease, as well at the abnormal vascular responses. Such therapies have yet to be identified. PMID- 8370244 TI - Modality-specific and amodal aspects of object perception in infancy: the case of active touch. AB - Three experiments investigated 4.5-month-old infants' perception of the unity and boundaries of haptically presented objects. When infants actively explored the two handles of an unseen object assembly, perception of the unity of the assembly depended on the handles' motion. Infants perceived a single, connected object if the handles moved rigidly together, and they perceived two distinct objects if the handles underwent relative vertical or horizontal motion. When infants passively explored the same object assembly undergoing the same motions, object perception appeared to be indeterminate. The findings of the active motion experiments accord with the findings of studies of visual object perception and suggest that object perception depends on amodal processes, operating on representations of either seen or felt surface motions. The findings of the passive motion experiments nevertheless suggest a difference between visual and haptic perception: for infants as for adults, haptic perception is enhanced by the active production of surface motion. PMID- 8370247 TI - Diagnosis, etiology, and therapy of fibromyalgia. PMID- 8370248 TI - Giant cell tumor of bone. PMID- 8370249 TI - Anabolic-androgenic steroids: use and abuse. PMID- 8370250 TI - Pediatric bone tumors. AB - A variety of benign and malignant bone tumors can affect the metabolically active pediatric skeleton. A thorough investigation with pertinent imaging studies can establish an appropriate differential diagnosis and frequently allows distinction between benign and malignant tumors. By using a multidisciplinary approach to the treatment of malignant tumors, a number of advances have been made. Further research is needed to gain more understanding and improve on the remarkable advances of the past 20 years. PMID- 8370251 TI - Extent and severity of periodontal destruction based on partial clinical assessments. AB - The aim of the present study was (i) to identify the 10 approximal tooth sites that provide Extent and Severity estimates of clinical attachment loss which are maximally coherent to the full mouth scores, and (ii) to evaluate the applicability of such a partial recording system. Data from two subject samples, comprising 192 subjects aged 30-64 yr (sample A) and 175 subjects aged 35-80 yr (sample B), were involved in the development and the evaluation of the system, respectively. Approximal probing attachment loss (PAL) measurements were available from all subjects. A PAL value of > 1 mm was required for a tooth site in order to qualify for the Extent and Severity computations. A full mouth bivariate Extent and Severity Index (FESI) was firstly calculated for every subject in sample A. Multiple regression models applied on data derived from the same sample identified the 10 approximal tooth sites which provided the best correlation to the full-mouth scores (correlation coefficients between partial and full mouth scorings of Extent and Severity 0.85 and 0.88, respectively). All tooth types were found to be represented in this set of sites and the ratio of mesial/distal sites was 6/4. The applicability of a partial recording system (PESI) based on these sites was evaluated in sample B. Fully comparable estimates between PESI and FESI values were obtained, but the degree of correlation varied at different ages. Further adjustments by means of regression models failed to increase the validity and reliability of the PESI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370252 TI - Juvenile periodontitis--pattern of progression and relationship to clinical periodontal parameters. AB - The present investigation was carried out 1) to identify subjects with juvenile periodontitis (JP) in a group of schoolchildren from a community with a high prevalence of periodontal diseases and with no access to preventive dental care, and 2) to study the clinical features of the disease and the progression pattern during a period of 1 yr, and the relationship of JP to clinical periodontal parameters. The periodontal condition of a group of 502 Iraqi schoolchildren (260 girls and 242 boys) was assessed radiographically and clinically at baseline. Children showing > or = 3 mm arc-shaped angular radiographic bone loss at the proximal surfaces of two or more first molars and who showed clinical attachment loss at the same sites were regarded as JP patients. A second group of children with no signs of JP were randomly chosen from the study material. One year later, the JP and the non-JP groups were re-examined radiographically and clinically to assess plaque, gingivitis and presence of calculus. The results showed that nine children (1.8%) had JP. The ratio of girls to boys was 3.5:1, and of localized to generalized forms 2:1. Mesial surfaces of first molars were more often affected than distal surfaces. Clinical assessments showed a more profound loss than was depicted radiographically. All JP patients exhibited evidence of periodontal disease progression during the following year. There were no differences between JP and non-JP children with respect to gingival inflammation, dental plaque, or calculus deposits on teeth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370253 TI - CPITN, DMFT, and treatment requirements in a Nicaraguan population. AB - WHO basic methods were used to assess CPITN, DMFT, and treatment requirements in a population of 178 persons aged 12-64 yr living in urban and rural areas of Nicaragua. Two groups were examined: individuals presenting for dental treatment at health clinics (30%) and subjects chosen randomly at other locations (70%). Mean ages of both groups were similar although females were found in higher percentages among those presenting for dental care. With the exception of one young individual, all subjects had calculus in at least one sextant. About 26% of the subjects who presented for treatment had a > or = 6 millimeter pocket compared to about 14% of the remainder of subjects. The mean DMFT for health clinic subjects was 16.1 compared to 10.3 for subjects from other locations. Subjects presenting for treatment had twice as many missing teeth and a mean of 0.5 filled teeth compared to 2.4 filled teeth for other subjects. Subjects at the clinics were in greater need of restorative care and extractions, while subjects from other locations were found to have more teeth that did not require any treatment. Health clinic subjects reported more visits to the dentist in the last year than other subjects. Only 80% of those presenting for treatment owned a toothbrush compared to 97% of those examined in other locations, and the latter group reported brushing their teeth more frequently. Attrition was a commonly encountered tooth disorder with 53% of all subjects exhibiting this condition. PMID- 8370254 TI - Caries experience in Icelandic 12-year-old urban children between 1984 and 1991. AB - In order to evaluate trends in caries experience, a 20% random sample of 12-yr old residents of Reykjavik, Iceland (252 children) was examined clinically and radiographically in 1991 under conditions consistent with those of the survey conducted in 1984. In addition to caries data, frequency of toothbrushing and use of fluoride dentifrice were recorded. The mean DFT and DFS were 3.0 and 4.1, respectively. The decrease in caries experience reached 60% with an annual fall in DFS of nearly 10%. During the 7-yr period between examinations the decline in DFT and DFS scores averaged 5.2 and 8, respectively, the annual reduction amounting to 0.7 DF teeth or 1.1 DF surfaces per child. The ratio of approximal/occlusal caries and the proportion of approximal caries were similar in both surveys. Fourteen percent of the children were free from manifest caries in 1991, but only 2% in 1984. Polarization between low and high prevalence individuals had intensified. Ninety-five percent of the children brushed their teeth regularly and 97% reported using a fluoride dentifrice. PMID- 8370255 TI - Dental status of 12-year-olds treated in private practice and a school dental service. AB - Different ways of service provision frequently lead to different services being provided. In the School Dental Service (SDS) in Western Australia, all 5-15-yr olds are eligible for care free of charge and most avail themselves of the service. The parents of some children choose to use private dentists (typically copaying about 50% of the cost) and their children do not attend the SDS. This study aimed to compare the dental status of 12-yr-olds who attended private dentists with that of matched children enrolled in the SDS. Non-enrolled 12-yr olds in Perth (F- 0.8 mg/l) were identified and asked to provide background information and participate in clinical examinations. Each non-enrolled participant was matched with a classmate of the same sex. Of 184 non-enrolled children, 100 actually participated. Data on caries experience (DMFT and DMFS), fissure sealants and gingival health (CPITN) were collected by clinical examination. Analyses used Wilcoxon's signed rank, categorical and t-tests and simple linear regression. Caries prevalence was lower in non-enrolled children (0.31) than in enrolled (0.47). Caries experience was also lower in non-enrolled children (mean DMFT 0.71 vs. 0.95, ns). Enrolled children had more FT than non enrolled (Wilcoxon, P = 0.059) but the mean number of DT in each group was 0.14. Enrolled children had somewhat fewer fissure sealants than non-enrolled children but in enrolled children there was an apparent (P = 0.056) inverse relationship between number of fissure sealants and DMFT scores; this was not the case in the non-enrolled group, suggesting better targeting of fissure sealants in the SDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370256 TI - Assessment of diagnostic accuracy in caries detection: an analysis of two methods. AB - The quality of a diagnostic tool for caries detection is usually evaluated by quantification of observer performance using sensitivity and specificity values calculated from data obtained from ordinal caries depth rating scales. The application of Receiver Operating Characteristic (ROC) analysis has been restricted to the use of confidence rating scales. The aim of this investigation was to study the appropriateness of ROC analysis using caries depth ratings by comparing sensitivity and specificity values to parameters of diagnostic performance obtained by ROC analysis. In two recent reports, sensitivity and specificity values were utilized to express diagnostic accuracy of observer performance from specified caries diagnostic systems. The raw data from these investigations were subjected to ROC analysis in the current study. The results illustrated that ROC analysis, producing estimates of sensitivities for all specificities, yielded more comprehensive measures of diagnostic performance than single values for sensitivity and specificity. In particular, the area under the ROC curve constituted a clearly interpretable parameter representing the quality of diagnostic performance. PMID- 8370257 TI - Ethnicity and maternal education as risk indicators for dental caries, and the role of dental behavior. AB - The aim of this study was to assess differences in dental health between socioeconomic and ethnic groups in a cohort of 5-yr-old children born in 1982 and in a cohort of 11-yr-old children born in 1976. A further aim was to evaluate the putative role of dental behaviors as intervening factors between ethnicity and maternal education on the one hand and caries experience on the other. A secondary analysis was performed on data collected in a study monitoring the oral health of youths covered by public health insurance (Ziekenfonds) in the Netherlands. The results showed both ethnicity and maternal education to be indicators of caries risk in the primary dentition. For caries in the permanent dentition, only maternal education could be identified as a risk indicator. Dental behaviors were related to caries experience as well as to ethnicity and maternal education, though the evidence for the role of these dental behaviors as intervening factors was weak. It is concluded that the validity and reliability of the behavioral measurements might be questionable and that the mechanism underlying the differences in caries experience between the various groups is still little understood. PMID- 8370258 TI - Characteristics and treatment outcome of diagnostic subgroups of CMD patients: retrospective study. AB - The records of 193 randomly chosen patients with CMD referred 2.5 yr previously were examined retrospectively for anamnestic, clinical and radiological findings and observations related to treatment. These data were supplemented with information from questionnaires sent to all treated patients in which their opinion on the treatment outcome was asked. Within the patient group, four diagnostic subgroups were distinguished. Three subgroups consisted of patients with the diagnoses CMD with a mainly myogenous component, osteoarthrosis and internal derangement respectively, whereas the fourth subgroup consisted of patients who did not fit into one of these categories. Differences between the four groups were found concerning mean age, the prevalence of a limited range of motion, headache, psychosocial factors, loss of posterior tooth support and objective treatment outcome. The patients with CMD with a mainly myogenous component showed the highest percentages of CMD associated disorders, the least successful treatment outcome and the highest percentage of renewed treatment. The patients with internal derangement showed the lowest mean age, the highest prevalence of a limited range of motion and the best treatment outcome. The patients in the osteoarthrosis group showed the highest mean age and the highest percentage of loss of posterior tooth support. It may be concluded that the evaluation of diagnostic subgroups of CMD patients has to be preferred in the assessment of a heterogeneous group of patients with CMD. PMID- 8370259 TI - What do anxious patients think? An exploratory investigation of anxious dental patients' thoughts. AB - According to BECK's cognitive model of emotional disorders (1976) anxiety is associated with negative and threatening thoughts concerning the likelihood of personal danger. In the present study the content of thoughts of 32 anxious dental patients was investigated. Patients' mean score for the Dental Anxiety Scale was 17.1 (SD = 2.0). The average time period patients had not visited a dentist was 9.1 yr (SD = 8.7). Using semi-structured interviews 132 thoughts were explored. The mean number of thoughts reported per patient was 4.1 (SD = 1.6). Almost all patients reported thoughts in some way related to their fear. All patients except one reported self-verbalizations of a negative or catastrophizing nature. Nine different categories of the content of the thoughts were identified. Nine percent of the thoughts consisted of visual images. The largest category (23%) consisted of catastrophic thoughts about the patient's own functioning during dental treatment, e.g., thoughts about losing control, panicking and dying. Fifty-nine percent of the patients reported thoughts of this type. The findings provide support for BECK's cognitive model of emotional disorders. PMID- 8370260 TI - Prevalence study of tongue lesions in a Hungarian population. AB - The aim of the study was to assess the prevalence of tongue lesions in a district population, in Budapest, called regularly for X-ray lung examinations. Oral examinations of 7820 individuals were performed, 42% were over 60 yr of age, 42.9% were men and 57.1% women. Tongue alterations were found in 18.52% of the examined individuals, more frequently in women than in men. Lingua fissurata has been diagnosed in 8.8%, geographic tongue in 3.0% of the examined subjects. Atrophic lesions of the tongue were found in 6.37%, among them 5.42% central papillary atrophy (median rhomboid glossitis): 0.35% of the total sample. Manifest clinical symptoms of oral Candidiasis were found in 2.15% of the total sample, and in 4.28% of patients with tongue lesions. The occurrence of oral leukoplakia and lichen in patients with tongue lesions was respectively 0.47 and 0.07%. The prevalence of tongue alterations was consistent with the literary data, the oral screening attached to the X-ray lung examinations proved to be useful in detecting changes of the oral mucosa. PMID- 8370261 TI - Oral health status of a long-term-care, veteran population. AB - The Department of Veterans Affairs (VA) operates the largest, integrated health care system in the United States of America. The projected need for long-term care in the VA health care system parallels an expected increase in need for care in the United States, but precedes the need for care in the general population by 25-30 yr. The VA's Office of Dentistry, in an effort to estimate the resource requirements of this swelling group of veterans, initiated in 1986-7 an oral health survey of long-term care patients. The overall goals were to describe the oral health status of VA nursing home care units (NHCU) residents and to develop a methodology for estimating future dental health services utilization. This study describes the oral health status of the study population. Demographic and oral health data were collected for 650 long-term care residents of six VA NHCUs between October 1986 and July 1987. Data were collected on sociodemographic status, medical history, dental caries, periodontal diseases, oral soft tissue pathology, and the presence of dental prostheses. Caries and periodontal disease were evaluated using the United States National Institute of Dental Research Survey of Employed Adults and Seniors protocols. The oral health status of the population is described using DMF and ESI indices, the prevalence of oral lesions, levels of tooth loss, oral hygiene scores, and the status of existing dentures. Findings show moderate levels of untreated dental caries and periodontal disease and significant tooth loss which increased with age. A need for preventive therapy, restorative dentistry, conservative periodontal therapy, and prosthodontic care was evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370262 TI - Influence of age and gender on oral health and related behaviour in an independent elderly population. AB - Previous studies have been unable to determine the influence of advanced age on oral health because they included relatively few subjects, particularly men, over 75 yr of age. In this study a disproportionate and stratified random sample of subjects over 70 yr and living independently was selected from a list of voters in Vancouver, B.C. The sample of 521 elders was structured to provide similar numbers of men and women in three 5-yr age-groups. All of the subjects were interviewed, and 255 of them, representing a similar distribution of age and gender, were examined to investigate the influence of aging on oral health and related behaviour. In bivariate analyses neither age nor gender was associated significantly with oral health or complaints. The use of dental services during the preceding year was associated with female and younger subjects, while men and older subjects usually went to dentists only to relieve pain. Logistic regression in a multivariate model confirmed the importance of natural teeth in predicting the use of dental services (by improving the prediction from 60% to 73%). Other models offered less useful improvements in predicting complaints (64% to 70%) or oral health (56% to 60%). Overall the study demonstrates that the age and gender of independent elders have very little direct influence on the oral health or related behaviour established early in life. PMID- 8370263 TI - Oral health care for nursing home residents in The Netherlands--a national survey. AB - In order to be able to develop adequate oral health care programs for nursing home residents in The Netherlands, currently available arrangements and problems experienced by dentists participating in this field of dentistry were evaluated in a national survey. One questionnaire was mailed to the managements of all nursing homes and a second to all dentists known to be involved in nursing home dentistry. The response rates were very high. The study indicated that, in almost every nursing home, dental care for residents was available, at least in cases of dental emergency. On average the dentists were spending only limited time on nursing home dentistry. The majority of dentists examined or treated the residents only when either the patients or others experienced or discovered an oral health problem. In delivering this kind of care the dentists experienced a lot of problems. These findings suggest that the oral health care for nursing home residents in The Netherlands must be evolved by research, special training of dentists, and through development of special care programs. PMID- 8370264 TI - Impact of dental fluorosis on the perception of well-being in an endemic fluorosis area in Tanzania. PMID- 8370265 TI - Determining optimal levels of fluoride in drinking water for hot dry climates--a case study in Sri Lanka. PMID- 8370266 TI - Monkeys and mug shots: cues used by rhesus monkeys (Macaca mulatta) to recognize a human face. AB - We investigated the cues rhesus monkeys (Macaca mulatta) use to recognize a familiar human face. To manipulate facial cues, schematic faces were constructed with Identi-Kit materials derived from mug shots. The monkeys (N = 4) spontaneously classed Identi-Kit as faces on initial presentations. The monkeys then learned to distinguish one Identi-Kit face, the standard, from others. Panel presses indicated recognition of the standard face. Eye movement recordings revealed that the monkeys predominantly fixated on the eyes of the standard face. When the standard face was transformed by removing, altering, or reorienting its features, only alterations of eyes or brows lowered recognition; removal of eyes, brows, nose, or lips did not. Responses to rotated, inverted, and scrambled versions of the standard face varied but generally disrupted recognition. We concluded that features and configuration were used to recognize the human face. PMID- 8370267 TI - Auditory frequency generalization and a failure to find octave generalization in a songbird, the European starling (Sturnus vulgaris). AB - Many species of songbirds have absolute pitch perception. They memorize tones when discriminating between sequences and fail to generalize to novel frequency ranges. I examined frequency generalization in starlings (Sturnus vulgaris) that were trained to discriminate between individual frequencies. Starlings were tested for frequency generalization after training on 2- and 3-tone discriminations. There was no evidence for octave generalization, which is a hallmark of human absolute pitch perception. This suggests that avian absolute pitch perception must not be interpreted as identical with that in humans. A control experiment with 1-tone discriminations indicated that the presence of lit response keys affects the shape of the generalization gradients. Lit response keys are a common feature in avian auditory perception experiments, and this control experiment cautions that results may be affected by this seemingly minor procedural change. PMID- 8370268 TI - Imitation in free-ranging rehabilitant orangutans (Pongo pygmaeus). AB - We made an observational study of spontaneous imitation in orangutans (Pongo pygmaeus). Previous studies may have underestimated great apes' imitative capacities by studying subjects under inhibiting conditions. We used subjects living in enriched environments, namely, rehabilitation. We collected a sample of spontaneous imitations and analyzed the most complex incidents for the likelihood that true imitation, learning new actions by observing rather than by doing, was involved in their acquisition. From 395 hr of observation and other reports on 26 orangutans, we identified 354 incidents of imitation. Of these, 54 complex incidents were difficult to explain by forms of imitation based on associative processes grounded in experimental learning alone; they were, however, congruent with acquisition processes that include true imitation. These findings suggest that orangutans may be capable of true imitation and point to critical eliciting factors. PMID- 8370269 TI - Posture and reaching in chimpanzees (Pan troglodytes) and orangutans (Pongo pygmaeus). AB - Hand preference in reaching was assessed under 2 postural adjustment conditions in 40 chimpanzees (Pan troglodytes) and 9 orangutans (Pongo pygmaeus). The postural conditions were quadrupedal and upright, during which reaching for food was scored on a minimum of 50 trials. Results indicated no population preference during quadrupedal reaching but a right-hand population preference was found during upright reaching. There were no significant effects of age or sex on either the direction or strength of hand preference. Early rearing history affected the strength of hand preference but not direction. The results suggest that posture is an important factor in the assessment of hand preference in great apes and may have important evolutionary consequences. PMID- 8370270 TI - Time-dependent decisions in dogs (Canis familiaris). AB - We investigated whether the foraging decisions of dogs (Canis familiaris) were time dependent and consistent with a temporal weighting rule (TWR) for maximizing the reliability of information. Dogs were given information about patches whose qualities varied over time. To simulate natural conditions, we interposed interruptions at selected points in foraging. Patch choices were time dependent and closely matched the predictions of TWR. Dogs relied on very recent information when available, but with increasing delays they used patch averages. TWR may be a general solution to problems faced by foragers in variable environments. PMID- 8370271 TI - Processes of social learning in the tool use of chimpanzees (Pan troglodytes) and human children (Homo sapiens). AB - Common chimpanzees (Pan troglodytes) and 2-year-old human children (Homo sapiens) were presented with a rakelike tool and a desirable but out-of-reach object. One group of subjects observed a human demonstrator use the tool in one way, and another group observed a demonstrator use the tool in another way. Children in both cases did what the model did. Chimpanzee subjects, however, behaved identically in the 2 model conditions. Both groups performed better than subjects who saw no demonstration. This pattern of results suggest that the chimpanzees were paying attention to the general functional relations in the task and to the results obtained by the demonstrator but not to the actual methods of tool use demonstrated. Human children were focused on the demonstrator's actual methods of tool use (her behavior). The different social learning processes used by the 2 species have implications for their different forms of social organization. PMID- 8370272 TI - Caregiving in virgin mice (Mus musculus): effects of biparental care and exposure to a second litter during preweaning development. AB - I examined the effects of early family unit conditions on later parenting behavior in laboratory mice (Mus musculus). I challenge previous studies that claim to show enhancing effects of biparental care on offspring parental responsiveness by raising mice with a male parent either present (MPP) or absent (MPA) during preweaning development. The results of those studies are confounded because MPP mice also have a second litter present (SLP) and MPA mice do not (SLA). Thus, the findings may have been due to the presence of second litter and not to the presence of the male parent. In this experiment I show that when offspring raised in different family units are tested as virgins with stimulus pups, more SLP mice are parental than SLA mice, and fewer SLP mice bite newborn pups than do SLA mice. Thus, results of previous studies are due to second litter exposure and not biparental care. PMID- 8370273 TI - Development of spontaneous classificatory behavior in chimpanzees (Pan troglodytes). AB - I investigated the development of spontaneous classificatory behavior in 5 chimpanzees (Pan troglodytes) tested at different ages and analyzed subjects' spontaneous constructive interactions with sets of logically structured objects. The results show that chimpanzees possess a natural capacity to react to similarities and differences among test stimuli and construct classes. The general progression of their classificatory development is very similar to that reported for human infants from 6 to 24 months. In both species, classification progresses from constructing single classes by different properties of objects to constructing single classes by similar or identical properties of objects. In addition, like humans, older chimpanzees spontaneously coordinate relations of similarities between sets and construct 2 class-consistent groupings. Chimpanzees' results are compared with those from a similar study with capuchins and macaques. PMID- 8370274 TI - Memory for individual scent in hamsters (Mesocricetus auratus) as assessed by habituation methods. AB - The memory of hamsters (Mesocricetus auratus) for the flank scent of other male hamsters was investigated in a series of habituation experiments. In 2 types of habituation tasks (Experiments 1 and 2), male hamsters habituated to the flank scent of 1 male and then increased their level of investigation to that of a novel male; similar results were obtained when the intervals between trials ranged from 1 s to 2 days. When the test trial was 10 or 21 days after habituation (Experiment 3), males discriminated between familiar and novel flank scents at 10 days but not at 21 days. The results demonstrate recognition of familiar and unfamiliar individual odors and excellent memory for these differences. Habituation techniques yield extremely robust results and may be useful for investigations of other aspects of individual signatures. PMID- 8370275 TI - Processing of ordinality and transitivity by chimpanzees (Pan troglodytes). AB - Three chimpanzees (Pan troglodytes) were trained to discriminate among pairs of boxes in an ABCDE-ordered series. The 2nd member of each pair was reinforced, until all 4 training pairs were learned. During novel tests the nonadjacent BD pair was presented, and all 3 animals reliably selected D. In Experiment 2, numerals 1-5 served as stimuli. One chimpanzee reliably selected the larger numeral 4 during testing with a nonadjacent pair (2-4), and 2 chimps showed no preference. In a 2nd phase, the same chimp demonstrated proficiency at reversing the task, reliably selecting the smaller of the 2-4 pair. In Experiment 4, after additional training, a 2nd test, which included novel test pairs composed of numbers that had not been used during training, was completed. Two of 3 animals were 100% correct on Trial 1 for all novel pairs. The results suggest that chimpanzees with experience in number concepts may recognize the ordinal character of numbers. PMID- 8370276 TI - Communal reproductive success in rats (Rattus norvegicus): effects of group composition and prior social experience. AB - We compared the reproductive success and maternal behavior of sibling pairs of female Long-Evans rats (Rattus norvegicus) housed together from birth (familiar) to that of pairs of unrelated females housed apart during development (unfamiliar). Sires either remained in the colonies through weaning of their pups or were removed before parturition. Familiar animals reared more pups to weaning, were more likely to share in caring for their pups, and were less likely to exhibit infanticide than were unfamiliar ones. The presence of males in cages with pups had no direct effect on the reproductive success of females, but female pairs housed with males spent less time than female pairs housed alone caring for pups together in a combined nest. Conflicting evidence for communal rearing in populations of wild rats may reflect differences in the genetic relatedness or early social experience of female rats. PMID- 8370277 TI - NONMEM version III implementation on a VAX 9000: a DCL procedure for single-step execution and the unrealized advantage of a vectorizing FORTRAN compiler. AB - There is great interest within the FDA, academia, and the pharmaceutical industry to provide more detailed information about the time course of drug concentration and effect in subjects receiving a drug as part of their overall therapy. Advocates of this effort expect the eventual goal of these endeavors to provide labeling which reflects the experience of drug administration to the entire population of potential recipients. The set of techniques which have been thus far applied to this task has been defined as population approach methodologies. While a consensus view on the usefulness of these techniques is not likely to be formed in the near future, most pharmaceutical companies or individuals who provide kinetic/dynamic support for drug development programs are investigating population approach methods. A major setback in this investigation has been the shortage of computational tools to analyze population data. One such algorithm, NONMEM, supplied by the NONMEM Project Group of the University of California, San Francisco has been widely used and remains the most accessible computational tool to date. The program is distributed to users as FORTRAN 77 source code with instructions for platform customization. Given the memory and compiler requirements of this algorithm and the intensive matrix manipulation required for run convergence and parameter estimation, this program's performance is largely determined by the platform and the FORTRAN compiler used to create the NONMEM executable. Benchmark testing on a VAX 9000 with Digital's FORTRAN (v. 1.2) compiler suggests that this is an acceptable platform. Due to excessive branching within the loops of the NONMEM source code, the vector processing capabilities of the KV900-AA vector processor actually decrease performance. A DCL procedure is given to provide single step execution of this algorithm. PMID- 8370278 TI - A qualitative model of the dynamics of blood glucose and its hormonal control. AB - A qualitative model of the short term glucose regulation system is presented. The model is based on the qualitative process theory, based on the concept of physical process defined by the property of causing changes in objects over time. The model has been successfully validated on inputs of several tests. It is intended to employ this model within a comprehensive system encompassing qualitative and quantitative aspects of modelling, building an environment useful for new treatment planning and for education. PMID- 8370279 TI - Knowledge-based client-server approach to structural information retrieval: the Digital Anatomist Browser. AB - Structural information can be defined as data and knowledge about biological objects ranging in size from molecules to the whole body. A framework is described for organizing structural information around a well-defined set of terminology and semantic relationships, and for disseminating multimedia structural information by means of a wide-area information server that is accessible over the internet. A Macintosh-based client of this server, called the Digital Anatomist Browser, has been used to teach neuroanatomy for the last 2 years. The client-server approach provides each student unlimited access to a rapidly growing knowledge base of structural biology that, while immediately useful for anatomy teaching, has the potential to be an organizing framework for other kinds of medical knowledge as well. PMID- 8370280 TI - DREAM: a shell-like software system for medical data analysis and decision support. AB - A software system was designed whose aim is to support everyday scientific research of physicians in different fields of medicine. DREAM is a shell-like tool which can be customized embedding in it the desirable structure of a particular medical problem. Various basic statistical analyses are provided along with the decision support capabilities. The decision aid is proposed in two steps -feature selection and classifier design. Genetic algorithm is implemented as the feature selection procedure. The classifier design option includes crisp and fuzzy k-Nearest Neighbors rule and a two-level classification scheme based on majority rule on the votes of several first-level k-Nearest Neighbors classifiers. The system's performance is illustrated with a database from aviation medicine. PMID- 8370281 TI - Peak identification of auditory brainstem responses with multi-filters and attributed automaton. AB - An attributed automaton, a special case of attribute grammar, is a flexible tool in pattern recognition. It allows the utilization of contextual information from previously analyzed patterns in the analysis of the current pattern, and offers the possibility of describing those structural characteristics of patterns which cannot be described by classic methods of syntactic pattern recognition. Auditory brainstem responses are routinely used in audiology and otoneurology. Many studies on using the spectral analysis of averaged auditory brainstem responses have described at least two frequency bands, corresponding to the slow and fast components. Selective non-recursive digital filters for each frequency band in the spectrum of the auditory brainstem response have revealed enhancement or attenuation of components, depending on the band. In this study, multi-filters and an attributed automaton were combined for the identification of peaks. PMID- 8370282 TI - A software simulation of tibial fracture reduction with external fixator. AB - In modern orthopaedic practice, circular external fixators are frequently preferred to plaster cast for various reasons. The realignment of the two fractured bone segments is usually performed under a continuous fluoroscopy checking which involves a long radiation exposure time for both patients and surgeon. In order to overcome this problem, a computer controlled external fixator is under development. One relevant problem which this project faced in its initial stage was the difficulty to define in geometrical terms the manual reduction trajectory normally adopted by the surgeon. Basically it was a typical problem of empirical knowledge transfer from the surgeon to the engineer. Thus, it was necessary to create a common ground where the two experts could carry out the necessary analyses in order to define an empirical algorithm capable of suggesting a correction trajectory. The problem was solved by developing a simulation program called S.E.R.F. (Simulation Environment of a Robotic Fixator) provided with an extremely powerful graphic output, able to visualize the whole reduction trajectory from any viewpoint in space. The authors suggest the use of this kind of tool every time the techno-clinical information exchange is a critical issue. PMID- 8370283 TI - A computer program for non-parametric receiver operating characteristic analysis. AB - Sensitivity and specificity are key measures of the performance of a given test in detecting a given disorder. For tests yielding numerical scores, sensitivity and specificity usually vary inversely over the range of theoretically possible cutoff scores, complicating the task of quantifying and comparing the diagnostic accuracy of tests. Receiver Operating Characteristic analysis (ROC) approaches this problem by plotting the curve of sensitivity versus 1-specificity for all possible cutoff scores of the test. The area under the ROC curve (AUC) can be used to describe the diagnostic accuracy of the test. Parametric and non parametric methods exist that allow the calculation of the AUC and the comparison of tests. A disadvantage of parametric formulations is the assumption of a normal or Gaussian distribution of test scores. The present article presents a computer program that utilizes non-parametric formulations that do not require the normal distribution of test scores. The program calculates the sensitivity and specificity of a test at all possible cutoff scores, plots the ROC curve, calculates the AUC, its standard error and 95% confidence limits, and allows the comparison of tests on independent and correlated samples. PMID- 8370284 TI - A new PAGE in mechanical ventilation? PMID- 8370285 TI - Medical direction of emergency medical service systems: a full-time commitment whose time has come. PMID- 8370286 TI - Nitric oxide as a target for therapy in septic shock. PMID- 8370287 TI - Regional blood flow and oxygen transport: implications for the therapy of the septic patient. PMID- 8370288 TI - Does resuscitative hypothermia protect the ischemic brain? PMID- 8370289 TI - Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome: a prospective, randomized, controlled study. AB - OBJECTIVE: To determine the efficacy of perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome. DESIGN: Prospective, randomized, controlled study. SETTING: State University of New York at Buffalo, School of Medicine and Biomedical Sciences. SUBJECTS: Eleven premature lambs with respiratory distress syndrome, delivered by cesarean section. INTERVENTIONS: Five lambs were supported by conventional mechanical ventilation alone. Six lambs were switched to perfluorocarbon-associated gas exchange after 60 to 90 mins of conventional mechanical ventilation. Perfluorocarbon-associated gas exchange was accomplished by instilling a volume of liquid perfluorocarbon equivalent to normal functional residual capacity (30 mL/kg) into the trachea, performing 3 to 4 mins of tidal liquid ventilation, and, at end-expiration, with liquid functional residual capacity of 30 mL/kg remaining in the lung, reconnecting the animal to the volume ventilator for gas tidal volumes. MEASUREMENTS AND MAIN RESULTS: Serial arterial blood gases and lung mechanics were measured. While receiving conventional ventilation, all animals developed progressive hypoxemia, hypercarbia, and acidosis. However, in the perfluorocarbon-associated gas exchange group, within 5 mins of the initiation of perfluorocarbon-associated gas exchange, mean PaO2 increased four-fold, from 59 +/- 6 torr (7.9 +/- 0.8 kPa) during conventional ventilation to 250 +/- 28 torr (33.3 +/- 3.7 kPa; p < .05) during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (268 +/- 38 torr; 35.7 +/- 5.1 kPa; p < .05). Mean PaCO2 decreased progressively from 62 +/- 4 torr (8.3 +/- 0.5 kPa) during conventional ventilation to 38 +/- 3.3 torr (5.1 +/- 0.4 kPa) at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean pH concomitantly increased. Dynamic compliance increased three fold within 15 mins of instituting perfluorocarbon-associated gas exchange, from 0.31 +/- 0.02 mL/cm H2O during conventional ventilation to 0.90 +/- 0.11 mL/cm H2O during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean peak expiratory flow and mean expiratory resistance were essentially unchanged during perfluorocarbon-associated gas exchange as compared with conventional ventilation in the same group. CONCLUSIONS: We conclude that perfluorocarbon associated gas exchange, which employs liquid functional residual capacity and gas tidal volumes delivered by a conventional ventilator, can facilitate oxygenation and CO2 removal, and dramatically improve lung mechanics in the premature lamb with respiratory distress syndrome. PMID- 8370290 TI - Effect of full-time, specialized physician supervision on the success of a large, urban emergency medical services system. AB - OBJECTIVES: Despite the universal proliferation of emergency medical services programs throughout the United States since 1970, only a few have ever documented a valid lifesaving effect, particularly in large, urban centers. The purpose of this study was to demonstrate the effect of specialized physician supervision on the effectiveness of an emergency medical services system. DESIGN: Prospective, cohort study. SETTING: Large, urban municipality (population 2 million). PATIENTS: Evaluation of victims of out-of-hospital sudden cardiac death cases, before (n = 152) and after (n = 200) the introduction of specialized physician supervision for the emergency medical services system. INTERVENTIONS: The hiring of a full-time, salaried emergency medical services system physician whose principal duties would be to provide intensive individualized training, direct operational supervision, and continuous system monitoring, including frequent on scene oversight of emergency medical services personnel. MEASUREMENTS AND MAIN RESULTS: Comparison of existing hospital discharge rates for out-of-hospital sudden cardiac death cases to those rates achieved 5 yrs after recruitment of the specialized emergency medical services system physician. A dramatic increase in hospital discharge rates was demonstrated for sudden death patients presenting with ventricular fibrillation, from zero at year 0 (0 of 152 patients survived), to 21% (42 of 200 patients) by year 5 (p < .001). This result was achieved despite the fact that all other related factors (budget, paramedic numbers, response times) significantly worsened during the comparison periods. CONCLUSIONS: The introduction of the new factor into the emergency medical services system (specialized physician supervision) was associated with significantly improved patient outcome. In view of current suboptimal outcome statistics found in most municipal emergency medical services programs across the United States, future goals of medical community leaders should be directed at efforts to properly train, certify, and establish appropriate positions for physicians who specialize in emergency medical services system supervision. PMID- 8370291 TI - L-arginine pathway in the sepsis syndrome. AB - OBJECTIVE: To investigate the role of nitric oxide in the regulation of vascular tone in patients with the sepsis syndrome. DESIGN: Prospective, intervention study. SETTING: Tertiary care hospital. PATIENTS: Fifteen patients admitted to our medical intensive care unit with the diagnosis of sepsis syndrome by defined criteria. INTERVENTIONS: Eight patients received N omega-nitro-L-arginine (20 mg/kg, iv bolus) followed by L-arginine (200 mg/kg, iv bolus). Seven patients received L-arginine alone (200 mg/kg). MEASUREMENTS AND MAIN RESULTS: In the first group, hemodynamic and oxygen transport variables were recorded at baseline, during 45 mins after the injection of N omega-nitro-L-arginine, and during 45 mins after the administration of L-arginine. In the second group, hemodynamic parameters were recorded at baseline and during 15 mins after the administration of L-arginine. Data are mean +/- SEM. The administration of N omega-nitro-L-arginine was followed by hypertension (mean blood pressure increased from 89 +/- 8 to a maximum of 140 +/- 12 mm Hg) accompanied by a decrease in cardiac index (from 3.51 +/- 0.39 to a minimum of 2.65 +/- 0.21 L/min/m2) and an increase in right atrial and pulmonary artery occlusion pressure. Systemic vascular resistance index increased from 1871.1 +/- 302.3 to 3825.6 +/- 244.4 dyne.sec/cm5.m2, and pulmonary vascular resistance increased from 533.2 +/- 125.8 to 816.0 +/- 117.3 dyne.sec/cm5.m2. These changes induced by N omega-nitro-L-arginine were reversed by the administration of L-arginine. The administration of L-arginine to another group of patients caused transient hypotension (from 103 +/- 6 to 81 +/- 10 mm Hg) and an increase in cardiac index (from 3.57 +/- 0.15 to 4.74 +/- 0.54 L/min/m2). Both systemic and pulmonary vascular resistance indices decreased (from 1987.6 +/- 163.9 to 1251.4 +/- 231.5 dyne.sec/cm5.m2, and from 486.1 +/- 65.2 to 380.5 +/- 70.3 dyne.sec/cm5.m2). Parallel to the increase in oxygen transport due to the increase in cardiac output, oxygen consumption index increased significantly 1 min after L-arginine (from 127.0 +/- 19.0 to 182.5 +/- 37.3 mL/min/m2). All mentioned changes were statistically significant (p < .05). CONCLUSIONS: A continuous basal release of nitric oxide plays a role in the regulation of systemic and pulmonary vascular tone in patients with sepsis syndrome. L-arginine has systemic and pulmonary vasodilatory actions. PMID- 8370292 TI - Regional blood flow and oxygen transport in septic shock. AB - OBJECTIVE: To measure the blood flow distribution and regional oxygen transport in hyperdynamic septic shock during hypotension and after correction by vasopressor doses of dopamine or norepinephrine. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary care center. PATIENTS: Ten patients with hyperdynamic septic shock (ages ranging from 45.1 +/- 16.6 yrs) and a control group of 11 postoperative cardiac surgery patients (ages ranging from 54.8 +/- 7.9 yrs). INTERVENTIONS: Systemic and regional hemodynamics and oxygen transport were measured in ten patients with hyperdynamic septic shock during hypotension and after vasopressor therapy (norepinephrine or dopamine). Oxygen consumption (VO2) was measured by indirect calorimetry and splanchnic and leg blood flow with indocyanine green infusion. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow and VO2 (p < .05) were increased in septic shock during hypotension and during vasopressor therapy. Both dopamine and norepinephrine increased systemic blood flow and VO2 independently of the arterial lactate level. Despite the relatively small changes in systemic oxygen transport, major regional changes occurred in oxygen delivery and VO2, and these changes were unpredictable from systemic changes. CONCLUSIONS: Regional changes in oxygen transport in septic shock cannot be predicted from the changes in the whole body. The increased oxygen demand in the splanchnic region is the main risk factor for splanchnic tissue hypoxia in septic shock. PMID- 8370293 TI - Regional blood flow and oxygen transport in patients with the low cardiac output syndrome after cardiac surgery. AB - OBJECTIVE: To assess systemic and regional oxygen transport after open heart surgery in patients with the low cardiac output syndrome who are receiving vasoactive drugs and in patients with normal hemodynamics during spontaneous rewarming. DESIGN: Prospective, nonrandomized controlled trial. SETTING: Tertiary care center. PATIENTS: Sixteen patients aged 53.1 +/- 8.4 yrs were studied after coronary artery bypass operations: ten patients with a cardiac index of < 1.75 L/min/m2 and six control patients with a cardiac index of > 1.75 L/min/m2. INTERVENTIONS: The patients with a cardiac index of < 1.75 L/min/m2 received either dobutamine alone (n = 5) or in combination with nitroprusside (n = 5). The control patients with a cardiac index of > 1.75 L/min/m2 did not receive vasoactive treatment. The systemic oxygen consumption was measured by indirect calorimetry and the regional blood flow was measured by primed continuous infusion of indocyanine green. MEASUREMENTS AND MAIN RESULTS: Both splanchnic and femoral blood flows increased (p < .05) in parallel with cardiac output during vasoactive drug therapy. High splanchnic oxygen extraction in patients with low cardiac index and flow-dependent splanchnic oxygen consumption in some patients indicated marginal splanchnic oxygen delivery. In addition, femoral blood flow was low and oxygen consumption changed in parallel with oxygen delivery in patients with the low cardiac output syndrome. CONCLUSIONS: In low cardiac output syndrome after cardiac surgery, splanchnic oxygen delivery was marginal and was maintained at the expense of peripheral oxygen delivery. Dobutamine, both alone and in combination with sodium nitroprusside, improved splanchnic oxygen delivery. PMID- 8370294 TI - Effects of blood transfusion on oxygen transport variables in severe sepsis. AB - OBJECTIVE: To investigate whether increasing oxygen delivery (DO2) by increasing hematocrit results in increases in oxygen uptake (VO2) in septic patients with an abnormal DO2/VO2 relationship. DESIGN: Prospective, randomized, interventional crossover study. SETTING: Tertiary care hospital. PATIENTS: A consecutive sample of 16 patients admitted to the intensive care unit, who were diagnosed as having severe sepsis by defined criteria and who had a hemoglobin concentration of < 10 g/dL. INTERVENTIONS: Patients received, in random order, an infusion of dobutamine (10 micrograms/kg/min) and a blood transfusion (800 mL of packed red blood cells in 90 mins). Hemodynamic and oxygen transport variables were determined before and after each treatment, allowing at least 20 mins during the infusion of dobutamine to achieve the steady state. MEASUREMENTS AND MAIN RESULTS: Changes in DO2 and VO2 induced by each intervention were measured. Dobutamine significantly increased DO2 (48.5 +/- 6.9%; p = .0001) and VO2 (21.7 +/- 3.3%; p = .0001). Blood transfusion increased DO2 (21.4 +/- 4.3%; p = .005) but VO2 did not change significantly (2.2 +/- 4.1%). Correlation coefficients for the percent changes of DO2 and VO2 (r2 = .67, p = .001 for dobutamine; and r2 = 21, p = .07 for blood transfusion) were significantly different for each treatment (p = .0001). CONCLUSIONS: In patients with an abnormal DO2-dependent VO2, as shown by increases in VO2 brought about by an infusion of dobutamine, blood transfusion does not significantly increase VO2, despite significant changes in DO2. The VO2, in some critically ill patients, depends more on blood flow than on global DO2. PMID- 8370295 TI - An exploratory analysis of medication utilization in a medical intensive care unit. AB - OBJECTIVES: To evaluate patterns of medication use in a medical intensive care unit (ICU) and to explore relationships between drug use, patient age, admitting diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE II) scores, length of stay, and survival. DESIGN: Combination prospective and retrospective study. SETTING: Medical ICU in a large teaching institution. PATIENTS: Patient admissions (n = 191) to a medical ICU during a 4-month study period. INTERVENTIONS: The following data were collected: age, length of stay, diagnosis, physiologic variables necessary for APACHE II scores, medications administered, and survival. MEASUREMENTS AND MAIN RESULTS: The mean length of stay of the study patients was 5.2 +/- 9.8 days. Overall mortality rate was 33%. The mean age of survivors, 62.7 yrs, was significantly (p < .05) lower than that value for nonsurvivors (68.6 yrs). Postcardiopulmonary resuscitation (CPR) or -stroke patients had a mortality rate that was higher than the overall mortality rate (p < .05). APACHE II scores of > 19 were associated with a reduced survival rate when compared with the overall mortality rate. The mean daily and mean total number of medications administered per patient were 7.5 +/- 3.4 and 12.1 +/- 7.6, respectively. Antihypertensives/vasodilators and gastrointestinal prophylaxis medications were administered most commonly in 69% and 65% of patients, respectively. The median total drug use per patient was significantly greater in nonsurvivors vs. survivors (13 and 10, respectively, p < .02). There was a positive linear relationship between total medication use and log length of stay (r2 = .62). Patients admitted post-CPR or with seizures received the highest number of medications (p < .05). CONCLUSIONS: Patients admitted to the medical ICU receive multiple medications from a variety of pharmacologic classes. Prolonged length of stay, certain admitting diagnoses, and death are associated with increased medication administration. Age, certain admitting diagnoses, and APACHE II scores are significantly related to survival. PMID- 8370296 TI - Effect of extracorporeal membrane oxygenation on neutrophil function in neonates. AB - OBJECTIVE: To study the effect of long-term extracorporeal membrane oxygenation (ECMO) support on neutrophil function. DESIGN: A prospective, clinical investigation. SETTING: A pediatric intensive care unit. PATIENTS: Four groups of patients: ECMO group 1, newborns after 1 day of ECMO support (n = 10); ECMO group 2, newborns after 5 days of ECMO support (n = 6); group 3, normal newborns (n = 20); group 4, normal adults (n = 30). INTERVENTIONS: Two mL of heparinized blood was obtained from patients in each group. A modification of the Smith and Rommel technique was used to measure neutrophil phagocytosis and killing utilizing live Candida tropicalis as the test organism. Neutrophils were incubated for 90 mins in normal adult serum with live Candida. Viability of Candida after phagocytosis was tested by vital fluorochrome staining. Phagocytic index (the number of neutrophils with intracytoplasmic Candida divided by the total neutrophils) and candidicidal ratio (neutrophils with dead Candida divided by total neutrophils with Candida) were determined daily. MEASUREMENTS AND MAIN RESULTS: Neutrophils from ECMO group 1 (day 1) and ECMO group 2 (day 5) patients had significantly higher phagocytosis indices (72.8 +/- 20 and 76 +/- 18) and candidicidal ratios (0.15 +/- 0.1 and 0.16 +/- 0.09) compared with neutrophils from group 3 patients (normal neonates) (64 +/- 7 and 0.06 +/- 0.04). The phagocytosis indices were significantly lower in neutrophils from ECMO group 1 (day 1) and ECMO group 2 (day 5) patients compared with group 4 (adults) patients (86 +/- 9). However, the candidicidal ratios in neutrophils from ECMO groups 1 and 2 (ECMO day 1 and day 5) patients were equal to that value in group 4 (adults) (0.10 +/- 0.04). ECMO support for 5 days (ECMO group 2 vs. group 1) did not significantly change either the phagocytosis index or candidicidal ratio. CONCLUSIONS: Phagocytosis and intracellular killing by neutrophils of ECMO-supported neonates were significantly greater than those values found in normal newborns. ECMO support for 5 days produced no significant changes in neutrophil phagocytosis or killing. PMID- 8370297 TI - Inflicted versus accidental head injury in critically injured children. AB - OBJECTIVES: To assess the frequency of inflicted head injury in critically injured children; the severity of neurologic injury; the neurologic outcome; and the historical, socioeconomic, physical, and radiologic factors associated with inflicted head injury. DESIGN: Prospective clinical study. SETTING: Multidisciplinary pediatric intensive care unit (ICU). PATIENTS: Consecutive cases (n = 40) of severe head injury admitted to a pediatric ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fourteen (35%) of 40 cases of head injury were due to inflicted head injury. Eleven (79%) of 14 inflicted head injury cases were due to child abuse and three (21%) were due to neglect. The severity of neurologic injury, as measured by the admission Glasgow Coma Scale, was worse in cases of inflicted head injury (7.1 +/- 0.7 [SE] [inflicted] vs. 9.9 +/- 0.8 [accidental]; p = .04). Glasgow Outcome Scores were worse after inflicted head injury (2 +/- 1 inflicted] vs. 4 +/- 1 [accidental]; p = .004). In victims of child abuse, we found the combination of any two of the following three factors was associated with inflicted head injury: an inconsistent history/physical examination; retinal hemorrhages; or parental risk factors (alcohol or drug abuse, previous social service intervention within the family, or a past history of child abuse or neglect). CONCLUSIONS: This study confirms that severity of neurologic injury and neurologic outcome in cases of inflicted head injury are worse than in any other type of childhood head injury. We believe that a combination of any two of the above three risk factors may prove to be a reliable marker of inflicted head injury in children admitted to a pediatric ICU and will lead to an early and definitive diagnosis. PMID- 8370298 TI - Decreasing imposed work of the breathing apparatus to zero using pressure-support ventilation. AB - OBJECTIVES: To apply pressure-support ventilation with the goal of decreasing the imposed work of the breathing apparatus (endotracheal tube, breathing circuit tubing, and the ventilator's demand-flow system) to zero and to evaluate a clinical method of measuring the imposed work of breathing. DESIGN: A prospective evaluation of adult and pediatric patients receiving mechanical ventilatory support. SETTING: A surgical and a pediatric intensive care unit in a university hospital. PATIENTS: Fifteen patients (11 adult and four pediatric), who were diagnosed with acute respiratory failure from various etiologies, and who were intubated and spontaneously breathing, received continuous positive airway pressure and pressure-support ventilation. MEASUREMENTS AND MAIN RESULTS: Imposed work of the breathing apparatus was calculated by integrating pressure measured at the tracheal end of the endotracheal tube from a narrow air-filled catheter and the change in volume from a miniature pneumotachograph (flow sensor) positioned between the "Y" piece of the breathing circuit and the endotracheal tube. Pressure and volume signals were directed to a computerized, portable respiratory monitor (Bicore Monitoring Systems) that provides real-time display of the pressure-volume (work) loops and calculation of the imposed work. Imposed work was measured at 0 cm H2O pressure-support ventilation, and then incremental levels of pressure-support ventilation were applied until the imposed work decreased to zero. Imposed work decreased in a quadratic fashion after incremental levels of pressure-support ventilation (r = -.83 [r2 = .69]; p < .001). At pressure-support ventilation level of 0 cm H2O, the imposed work was 0.60 +/- 0.17 joule/L. At mean pressure-support ventilation levels of 13.5 +/- 4.8 cm H2O, imposed work decreased to 0 joule/L. CONCLUSIONS: Ideally, the imposed work of the breathing apparatus should be zero to decrease the afterload on the ventilatory muscles and, thus, the patient's work of breathing. Eliminating the imposed work is achieved using appropriate levels of pressure support ventilation. We describe an easily applied, practical method of measuring imposed work using a commercially available, portable, bedside respiratory monitor. We recommend that all patients diagnosed with respiratory failure and compromised pulmonary mechanics and who are intubated and breathing spontaneously, receive at least a minimal level of pressure-support ventilation that results in zero breathing apparatus-imposed work of breathing. PMID- 8370299 TI - Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. AB - OBJECTIVE: Previously, we documented that mild hypothermia (34 degrees C) induced immediately with reperfusion after ventricular fibrillation cardiac arrest in dogs improves functional and morphologic cerebral outcome. This study was designed to test the hypothesis that a 15-min delay in the initiation of cooling after reperfusion would offset this beneficial effect. DESIGN: Prospective, randomized, controlled study. SETTING: Animal intensive care unit. SUBJECTS: A total of 22 custom-bred coonhounds. INTERVENTIONS: Eighteen dogs underwent normothermic ventricular fibrillation arrest (no blood flow) of 12.5 mins, reperfusion with brief cardiopulmonary bypass, defibrillation within 5 mins, intermittent positive-pressure ventilation to 20 hrs, and intensive care to 96 hrs. Three groups of six dogs each were studied: group 1, normothermic controls; group 2, core temperature 34 degrees C from reperfusion to 1 hr; and group 3, delayed initiation of cooling until 15 mins after normothermic reperfusion, and 34 degrees C from 15 mins to 1 hr 15 mins after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Tympanic membrane temperature (which represented brain temperature) in group 2 reached 34 degrees C at 6 +/- 3 (SD) mins after reperfusion; and in group 3 at 29 +/- 1 mins after reperfusion. Best overall performance categories achieved (1, normal; 5, brain death) compared with group 1, were better in group 2 (p < 0.5) but not in group 3 (NS). Similar results were found with best neurologic deficit scores (0%, normal; 100%, brain death), i.e., 44 +/- 4% in group 1, 19 +/- 15% in group 2 (p < .01), and 38 +/- 9% in group 3 (NS). Total brain histologic damage scores (< 30 minimal damage; > 100 severe damage), however, were 150 +/- 32 in group 1, 81 +/- 13 in group 2 (p < .001 vs. group 1), and 107 +/- 17 in group 3 (p < .05 vs. group 1). CONCLUSIONS: Mild, resuscitative cerebral hypothermia induced immediately with reperfusion after cardiac arrest improves cerebral functional and morphologic outcome, whereas a delay of 15 mins in initiation of cooling after reperfusion may not improve functional outcome, although it may slightly decrease tissue damage. PMID- 8370301 TI - Device to limit inflation of a pulmonary artery catheter balloon. AB - OBJECTIVE: The most serious complication seen with pulmonary artery catheters is rupture of the pulmonary artery. The effectiveness of an external safety balloon added to the pulmonary artery balloon inflation port was tested. DESIGN: The external balloon is designed to inflate and absorb excess volume from the inflation syringe after the internal balloon contacts the vessel wall. When the catheter tip is in a small pulmonary artery, expansion of the external balloon indicates that the catheter tip is in a noncompliant or small vessel. SETTING: The external balloon was tested in a bench simulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pulmonary artery balloon was slowly inflated inside 2.6-, 3.0-, 4.7-, 8.6-, and 11.6-mm internal diameter polyvinyl chloride tubes, with and without the external safety device in place. Without the external balloon, the average balloon pressure was 1647 +/- 145 (SD) mm Hg in the 2.6-mm vessel. With the external balloon in use, the maximum pulmonary artery balloon pressure was 473 +/- 7.2 mm Hg in the 2.6-mm vessel. CONCLUSIONS: The external balloon can limit balloon pressures within the pulmonary artery and identify when excessive volumes are being forced into the pulmonary artery balloon. PMID- 8370300 TI - Sucralfate does not reduce the risk of acid aspiration pneumonitis. AB - OBJECTIVE: To study the pulmonary effects of aspirating a mixture of sucralfate in water and sucralfate in hydrochloric acid in an animal model of aspiration pneumonia. DESIGN: Prospective, randomized, controlled study with repeated measures. SETTING: University research laboratory. SUBJECTS: Thirty-two in situ, isolated, blood perfused porcine lung preparations. INTERVENTIONS: Five control preparations received no aspiration. Twenty-seven preparations received a standard aspiration of 1.5 mL/kg body of a) distilled water (n = 5), b) sucralfate in distilled water (n = 8), c) 1/10 normal hydrochloric acid (n = 6), and d) mixture of sucralfate in distilled water and hydrochloric acid (n = 8). MEASUREMENTS: The pH measurements were made of all aspirates. Lung weight, airway pressures, and pulmonary artery pressures were continuously monitored before and for 4 hrs after aspiration. Lung wet/dry weight ratio was measured at the completion of the study. RESULTS: The pH of sucralfate mixed with distilled water was 4.9, pH of 1/10 normal hydrochloric acid was 1.0, and pH of equal volumes of a sucralfate-water suspension mixed with hydrochloric acid was 1.5. Airway pressures and pulmonary arterial pressures increased in all aspirate groups over time compared with those values of control lungs. Control lungs gained 18 +/- 3 (SEM) g over 4 hrs and the wet/dry ratio was 4.951 +/- 0.310. Lungs aspirating distilled water gained 147 +/- 49 g and the wet/dry ratio was 5.198 +/- 0.120. Lungs aspirating sucralfate and distilled water increased their weight by 109 +/- 30 g and the wet/dry ratio was 5.380 +/- 0.076. Lungs aspirating a suspension of sucralfate and water and hydrochloric acid were similar to lungs aspirating hydrochloric acid alone with weight increases of 265 +/- 30 g and 346 +/- 81 g, and the wet/dry ratio of 7.011 +/- 0.273 and 7.230 +/- 0.390, respectively. CONCLUSIONS: Sucralfate has minimal acid buffering effect. Aspiration of sucralfate mixed with distilled water causes lung edema similar to aspiration of water alone. Aspiration of a sucralfate-water suspension mixed with hydrochloric acid causes severe lung edema. These results suggest that patients given sucralfate prophylaxis for stress ulceration are at risk for acid aspiration. PMID- 8370302 TI - Real-time gas-exchange measurement of oxygen consumption in neonates and infants after cardiac surgery. AB - OBJECTIVES: The purposes of this study were: a) to measure oxygen consumption (VO2) in ventilated neonates and infants after cardiac surgery, utilizing a real time gas exchange system; and b) to assess this new method by comparing the measured VO2 with calculated VO2 (using the Fick equation and simultaneously determined thermodilution cardiac output, measured hemoglobin, and measured mixed venous and arterial saturations). DESIGN: Prospective, comparison study. Comparison of measured VO2 and calculated VO2 using correlation coefficient, linear regression analysis, and bias and precision. SETTING: Cardiac intensive care unit in a children's hospital. PATIENTS: A total of 60 direct comparisons were made between measured and calculated VO2 in 15 patients (ages ranging from 4 days to 14.1 months with median age of 2.4 months) who were receiving mechanical ventilation after undergoing corrective cardiac surgery. INTERVENTIONS: a) Direct measurement of VO2 using gas exchange method involving a pneumotachograph and a gas sampling system; b) determination of cardiac output by the thermodilution technique; c) measurement of arterial and mixed venous oxygen content by blood sampling. MEASUREMENTS AND RESULTS: The absolute measured VO2 ranged from 19 to 154 mL/min with a mean of 52 +/- 32 mL/min (when indexed, the range was 81 to 367 mL/min/m2 with mean 185 +/- 69 mL/min/m2, or range 4.7 to 18.8 mL/min/kg with mean 10.4 +/- 3.3 mL/min/kg). While 34 (57%) of 60 measured VO2 values were within 10% of their respective calculated VO2 values, 58 (97%) of 60 were within 25%; the mean percent difference between measured and calculated VO2 values was 10.6 +/- 7.7%. In comparing the measured VO2 and calculated VO2, the correlation coefficient was good (r2 = .87; p < .01) and the linear regression equation was: measured VO2 = 1.1 x calculated VO2 -9.0 mL/min/m2. The mean difference, or bias, was 0 mL/min/m2 with precision of 26 and 52 mL/min/m2 (at 1 and 2 SD). As an alternative means of examining the measured VO2 data, we also directly compared the thermodilution cardiac output with cardiac output derived by using the measured VO2 and the Fick equation. The range of Fick-derived cardiac output was between 1.69 to 8.11 L/min/m2 (mean 3.72 +/- 1.56) and the range of thermodilution cardiac output was between 1.75 to 7.42 L/min/m2 (mean 3.71 +/- 1.36). The correlation coefficient between thermodilution cardiac output and Fick derived cardiac output was good with r2 = .88 (p < .01) and the linear regression equation was: thermodilution cardiac output = 0.81 x Fick-derived cardiac output + 0.71 L/min/m2. The bias was -0.01 L/min/m2 with a precision of 0.54 L/min/m2 at 1 SD (or 1.08 L/min/m2 for 2 SD). CONCLUSIONS: Measured VO2 using a gas-exchange system compared favorably with calculated VO2 values using the Fick equation and simultaneously obtained thermodilution cardiac output and arterial and venous oxygen concentrations. By employing this breath-by-breath gas-exchange system, real-time VO2 measurement in ventilated neonates and infants is now feasible. PMID- 8370304 TI - Fellowship programs in critical care medicine: 1994. PMID- 8370303 TI - Reperfusion injury after intestinal ischemia. AB - OBJECTIVE: Review the histologic and pathophysiologic alterations seen after intestinal ischemia and reperfusion. DATA SOURCE: Current literature review. STUDY SELECTION: The most pertinent, current, and representative articles describing results from both animal and human investigations are utilized and discussed. DATA SYNTHESIS: Postischemic intestinal tissue damage appears to be due to the formation of oxygen radicals and the activation of phospholipase A2. The initial source of oxygen radicals seems to be the hypoxanthine-xanthine oxidase system. Oxygen radicals react directly with poly-unsaturated fatty acids, leading to lipid peroxidation within the cell membranes. Indirectly, the radicals trigger the accumulation of neutrophils within the affected tissue initiating inflammatory processes that lead to severe mucosal lesions. Similarly, phospholipase A2 also initiates postischemic mucosal lesions. Phospholipase A2 is a hydrolytic enzyme capable of increasing formation of cytotoxic lysophospholipids within the tissue. Enhanced activity of phospholipase A2 also stimulates the production of prostaglandins and leukotrienes. Various substances (superoxide dismutase, catalase, dimethyl sulfoxide, allopurinol, and deferoxamine, etc.) are able to detoxify oxygen radicals or inhibit the mechanisms leading to their enhanced generation, thus attenuating the postischemic lesions of the mucosa. CONCLUSIONS: Oxygen radicals and the activation of phospholipase A2 during reperfusion seem to be instrumental for the development of hemorrhagic mucosal lesions after intestinal ischemia. Radical scavengers and phospholipase A2 inhibitors may prevent reperfusion damage of the intestine, even when the treatment starts during ischemia but before reperfusion. PMID- 8370305 TI - Spurious hemodynamic alterations resulting from light sensitive pressure transducers. PMID- 8370306 TI - Muscle relaxants in intensive care patients. PMID- 8370307 TI - Routine hypertonic saline in clinical practice: is it worth it? PMID- 8370308 TI - Reversal of midazolam sedation. PMID- 8370309 TI - Omeprazole and refractory stress-induced gastric mucosal hemorrhage. PMID- 8370310 TI - Cytoprotective effect of glycine in cold stored canine renal tubules. AB - Reperfusion injury has been suggested to cause delayed graft function in renal transplantation. Methods to reduce reperfusion injury could lead to improved clinical renal transplantation. Glycine has been shown to suppress reperfusion injury in rabbit renal tubules and rat hepatocytes. In this study we have determined the effects of glycine on viability of isolated canine renal tubules. Renal tubules were cold stored at 4 degrees C under hypoxic conditions for up to 96 h in the UW solution and rewarmed to 37 degrees C for up to 2 h under oxygenated conditions to simulate reperfusion of an organ after cold static storage. Short-term storage (24 to 48 h) did not cause membrane injury (leakage of lactate dehydrogenase (LDH)) on rewarming. However, after 72 and 96 h cold storage reperfusion injury was evident and LDH leakage increased from about 25% to 59 +/- 3% and 71 +/- 2% at 72 and 96 h cold storage, respectively. The presence of 3 mM glycine in the reperfusion medium suppressed injury to cold stored renal tubules. After cold storage for 72 and 96 h LDH leakage was reduced to control concentrations (31 +/- 3% and 29 +/- 1%, respectively). After cold storage for 72 h there was a reduction in ATP concentration in rewarmed renal tubules (3 nmol/mg protein at 48 h to 1.25 nmol/mg protein at 72 h). Also, there was a loss of mitochondrial functions including decreased stimulation of oxygen consumption by uncoupling of oxidative phosphorylation. Although glycine suppressed LDH leakage in renal tubules cold stored for 72 h it had no effect on the regeneration of ATP or mitochondrial functions, which remained depressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370311 TI - Cold- and cryopreservation of human liver and kidney slices. AB - Tissue slices may provide a rapid and economical way of determining cold ischemic effects on human liver and kidney cell viability and metabolism. In contrast to isolated hepatocyte cultures, tissue slices offer an in vitro system which more closely resembles the in vivo situation because of the differentiation and functional heterogeneity of the slice. In this study, human liver and kidney slices were cold stored for 10 days in Belzers University of Wisconsin (UW), Euro Collins, and Modified Sacks solutions. Another set of slices was cryopreserved at 1 degree C/min for liver and 12 degrees C/min for kidney using a 10% dimethyl sulfoxide/fetal calf serum (FCS) cryoprotectant solution. The cold- and cryopreserved slices were incubated in roller culture for 4 h using FCS as the media. Liver slice viability was assessed by K+ content, protein synthesis, gluconeogenesis, and urea synthesis. Kidney slice viability was assessed using K+ content, protein synthesis, and organic ion transport (PAH and TEA). Human kidney slices were cold preserved in UW for 4-6 days, while the human liver slices were preserved for 12-24 h depending on the viability parameter. Following cryopreservation, human liver slice viability was retained at between 65 and 90% of control values, while kidney slice viability was maintained between 70 and 90% of control values depending on the viability parameter. These results indicate that this human in vitro tissue slice system can be used to optimize preservation solutions and methods. The ability to cold- and cryopreserve human slices could facilitate the more efficient utilization of human tissue. PMID- 8370312 TI - Successful cryopreservation of fetal porcine proislets. AB - This study reports the cryopreservation of purified fetal pig proislets (FPP) which were isolated by a culture technique. The FPP were equilibrated with 2 M dimethyl sulfoxide (Me2SO), cooled at a rate of 0.25 degrees C/min to -40 degrees C, transferred to liquid nitrogen (-196 degrees C), stored for 2 h to 2 months at -196 degrees C, and thawed in a 37 degrees C water bath. The morphology of frozen thawed FPP was similar to that of noncryopreserved FPP. One hundred percent recovery of response capacity was achieved when tested with 16.7 mM glucose plus 10 mM theophylline. We have recently shown that streptozotocin is not toxic to FPP. Accordingly, we transplanted a standardized dose (10-15 mg/mouse) of either cultured of frozen-thawed FPP beneath the renal capsule of nude mice. Three to four weeks later the recipients of the FPP were rendered diabetic by iv streptozotocin. All of the mice transplanted with cultured FPP and seven of eight mice receiving cryopreserved FPP achieved normoglycemia, 74.8 +/- 32.9 and 54.7 +/- 8.1 days (P > 0.05) after transplantation. An intraperitoneal glucose tolerance test in the mice of both groups showed a flatter response to glucose compared to those of normal controls. Grafts removed from the mice with normoglycemia for > 3 weeks, in both groups, had the capacity to secrete insulin in response to 16.7 mM glucose alone and 16.7 mM glucose plus 10 mM theophylline during in vitro perifusion. Histological examination revealed that the extent of differentiation and development, in vivo of cryopreserved FPP was comparable with that of cultured FPP. These data indicate that cryopreservation, with the protocol used here, is successful in maintaining functional viability of frozen thawed FPP. This study is valuable for clinical islet transplantation research. PMID- 8370313 TI - Prostaglandin E2, interleukin-1 alpha, and potassium release from artificial human skin after freeze-thaw injury. AB - Living skin equivalent (LSE) was used to identify nonvascular aspects of freeze thaw injury to human skin cells. Pairs of transwell cell culture inserts, containing LSE, were washed twice for 30 min in maintenance media at 37 degrees C in a CO2 incubator and placed in two wells of a six-well assay tray (containing assay media). One specimen was maintained at room temperature. The other was cooled at 1 degrees C/min to -15 degrees C and rapidly rewarmed. Both were incubated for 24 h on fresh maintenance media at 37 degrees C in a CO2 incubator. This process was repeated producing 12 per group. Prostaglandin E2 (PGE2), interleukin-1 alpha (IL-1 alpha), and K+ were measured (mean +/- SE) in the assay medium, after the rewarming interval, and in the maintenance media after the 24-h incubation. Specimens were then processed for electron microscopy. After the rewarming interval, PGE2 (164.0 +/- 23.2 pg/0.1 ml), IL-1 alpha (24.3 +/- 2.2 pg/0.1 ml), and K+ (6.47 +/- 0.41 mM) released from frozen LSE were significantly increased compared to controls (PGE2 = 22.2 +/- 4.6 pg/0.1 ml, IL-1 alpha = 5.7 +/- 1.0 pg/0.1 ml, K+ = 4.32 +/- 0.02 mM). After the 24-h incubation, PGE2 and IL 1 alpha released by frozen LSE (PGE2 = 1126 +/- 208 pg/0.1 ml; IL-1 alpha = 80.6 +/- 6.8 pg/0.1 ml) remained significantly higher than controls (PGE2 = 229.0 +/- 45 pg/0.1 ml; IL-1 alpha = 4.9 +/- 0.7 pg/0.1 ml). At this time, K+ leakage from frozen LSE (4.39 +/- 0.03 mM) had returned to a normal range (control = 4.65 +/- 0.02 mM). Keratinocytes and, to a lesser extent, fibroblasts showed ultrastructural freeze-thaw damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370314 TI - Osmotic effects of dilution on erythrocytes after freezing and thawing in glycerol-containing buffer. AB - Red blood cells frozen in 1.7 M and particularly in 2.2 M of glycerol retain a high degree of integrity upon thawing as long as the dilution procedure of the cryoprotectant is slow and preferentially compensated by the addition of sorbitol. As the nonpenetrating cryoprotectant sorbitol induces initial cell shrinkage, cell swelling upon dilution of the cryoprotectants may not lead to hemolysis. However, rapid dilution of glycerol even with buffer containing up to 0.50 M of sorbitol cannot be achieved without provoking considerable hemolysis. Due to the relative slow rate at which glycerol leaves the cells, membrane damage to the younger cell populations remains considerable and is even more pronounced in the older cell groups. The dramatic osmotic changes occurring during the dilution process lead to the formation of aberrant cell populations as demonstrated by the red cell size frequency distribution curves. PMID- 8370315 TI - Comparative effects of cryosolvents on tubulin association, thermal stability, and binding of microtubule-associated proteins. AB - Organic cryosolvents essential for cryopreservation of living cells have a colligative effect on water properties, but also affect cellular structures such as the membrane, actin, or tubulin cytoskeleton. The effects of cryosolvents on actin and its binding proteins are starting to be well investigated. In parallel, tubulin assembly characteristics were investigated comparatively, with 0-30% 1,2 propanediol, dimethyl sulfoxide, or glycerol, and with or without microtubule associated proteins, at 37 or 4 degrees C. Tubulin association was monitored by spectrometry and sedimentation, providing the concentration in free protein, cold depolymerizable microtubules, and cold-resistant associations. At 37 degrees C, 1,2-propanediol and dimethyl sulfoxide induce a similar association level and cold stability of the assemblies. Glycerol yields a lower level of tubulin association. Cold stability of the assemblies requires the presence of solvent, the amount of which is modulated by microtubule-associated proteins (MAPs): 15% 1,2-propanediol or dimethyl sulfoxide, decreasing down to 10% with MAPs, or 10% glycerol with MAPs only. At 4 degrees C, some cold-stable association is promoted by 1,2-propanediol or dimethyl sulfoxide above 10-15%, in the presence or absence of MAPs, but not with glycerol. In addition, protein content of the various fractions obtained with MAPs and 30% solvent was examined by densitometry of electrophoresis gels. Cold-labile associations obtained at 37 degrees C with 1,2 propanediol or dimethyl sulfoxide are lacking in tubulin and enriched in tau proteins relative to control or glycerol. Associations formed at 37 degrees C and stable to subsequent cold treatment, or at 4 degrees C, regardless of the solvent, present a large tubulin content, as well as few tau proteins and high molecular-weight MAPs. PMID- 8370316 TI - Cryoprotective effect of egg yolk in cryopreservation of porcine embryos. AB - The objective of the present study was to assess the effect of egg yolk supplementation in solutions for either cooling or freezing of porcine embryos. In Experiment 1, porcine embryos collected on Day 3 to 7 (Day 0 = onset of estrus) were allocated to 12 experimental groups according to their developmental stages (four-cell to compact morula, early blastocyst to blastocyst, expanded blastocyst, and hatched blastocyst) and the concentrations of egg yolk (0, 5, and 10% (v/v)) for cooling to 0 degrees C. Whereas no embryos ranging from four-cell to blastocyst survived, the 10-min exposure to 0 degrees C despite egg yolk supplementation, expanded blastocysts and hatched blastocysts allocated to egg yolk-supplemented groups survived cooling to 0 degrees C. In Experiment 2, porcine expanded and hatched blastocysts collected on Day 6 or 7 were assigned to six experimental groups according to their developmental stages and the type of cryoprotectant used (10% glycerol, 11% Me2SO, and 10% propylene glycol) for freezing at -196 degrees C. All freezing solutions contained either 5 or 10% egg yolk. The embryos were equilibrated with one of the freezing solutions, cooled from 25 to -7 degrees C at 1 degree C/min, seeded at that temperature, then cooled to -36 degrees C at 0.3 degree C/min, and finally plunged into liquid nitrogen for storage. The frozen embryos were thawed by immersion in 37 degrees C water. After the cryoprotectants were removed by dilution, the embryos were cultured for 48 h to evaluate their viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370317 TI - Survival rate of frozen-thawed bovine IVF embryos in relation to exposure time using various cryoprotectants. AB - The relationship between cryoprotectant and exposure time on the development of IVF-derived embryos in culture after freezing and thawing was examined. Good to excellent quality Day 7 to 8 blastocysts and expanded blastocysts were suspended in 1.6 M propylene glycol (PG), 1.8 M ethylene glycol (EG), 1.1 M diethylene glycol, and 1.3 M ethylene glycol monomethyl ether (EME). In Experiment I, after 30 and 120 min of exposure, embryos were placed directly into culture medium and washed three times. Embryos were cocultured with cumulus cells in culture medium. After a 48-h culture, there were no significant differences in fully expanded, hatching, and hatched rates between the 30- and 120-min exposure to all four cryoprotectants except for the fully expanded rate with PG (55 vs 83%). In Experiment II, to compare the cryoprotective effects of the four cryoprotectants, embryos were exposed to each cryoprotectant for variable times from 10 to 120 min, seeded, and cooled to -30 degrees C at 0.3 degree C/min, plunged into liquid nitrogen for storage, and then thawed. Survival was measured by coculturing the embryos with cumulus cells in culture medium. There were no significant differences in development to hatched blastocysts of embryos exposed to either PG (27-42%) or EG (37-56%). The number of embryos developing after exposure to EME was similar to that in PG or EG when exposure time did not exceed 40 min (43 49%). Our findings suggest that the toxicity of different cryoprotectants is related to the exposure time and that PG and EG were relatively nontoxic as is exposure to EME for short periods. PMID- 8370318 TI - Further evidence for two modes of hypothermia damage. AB - The Arrhenius plot of inactivation (killing) rates of V-79 Chinese hamster cells exposed to hypothermia contains a break at about 8 degrees C, which corresponds to the minimum inactivation rate, implying that there are distinct hypothermic damage mechanisms above (Range I = 8 to +25 degrees C) and below (Range II = 0 to +8 degrees C) 8 degrees C. Several membrane-permeable hydroxyl free radical scavengers, N-acetylhomocysteinethiolactone (citiolone), dimethylthiourea (DMTU), and dimethyl sulfoxide (DMSO), were tested for their ability to protect cells exposed to hypothermic temperatures of 10 degrees C (Range I) or 5 degrees C (Range II) as a function of time in a system that is uncomplicated by previous hypoxia. Citiolone (3 mM) protected cells in Range I, but not in Range II. To date, citiolone is the only agent that protects in Range I. Adenosine was of no benefit in Range I. Glycine (5 mM) protected cells in Range II, but not in Range I. DMSO (10 mM) was ineffective in Range II, while DMTU (10 mM) protected cells in Range II, but not in Range I. The combination of DMTU and citiolone had a synergistic protective effect on the cells during 10 degrees C exposure (Range I). However, the combination of DMTU and citiolone is neither synergistic nor additive at 5 degrees C (Range II). PMID- 8370319 TI - Freeze drying of biomaterials for the medical practice. AB - Experimentally determined thermophysical characteristics of the new antifibrinolytic bacteriostatic biomedical preparation CAPROCOL are reported. Experimental and theoretical temperature histories at selected locations in a sample of CAPROCOL undergoing freeze drying are compared. The advance of the moving phase interface is also predicted. PMID- 8370320 TI - Penetration of clarithromycin into human saliva. AB - The concentrations of clarithromycin after a single oral dose of 500 mg were determined in serum and saliva of ten healthy adult volunteers. After 2 h, the levels were 4.04 +/- 1.14 (SD) mg/l in serum and 2.72 +/- 0.87 mg/l in saliva. After 7 h these values were 1.98 +/- 0.65 and 1.21 +/- 0.34 mg/l, respectively, and at the end of the dosing interval of 12 h, 0.95 +/- 0.38 and 0.73 +/- 0.35 mg/l, respectively. In comparison, amoxicillin (a 750-mg single dose) showed a much faster decline of serum levels and was virtually undetectable in saliva. PMID- 8370321 TI - Pharmacokinetic profile of fosfomycin trometamol. AB - The pharmacokinetics of fosfomycin trometamol has been assessed in 12 healthy volunteers given oral doses of 2, 3, and 4 g of fosfomycin and 3 g intravenously of fosfomycin as fosfomycin sodium, all in the fasting state. The assay was microbiological (Proteus mirabilis ATCC 21100). There was a gradual rise in both peak serum concentrations and total area under the curve by rising oral doses, from 16.0 mg/l and 106.7 mg x h/l, after 2 g to 30.9 mg/l and 189.7 mg x h/l after 4 g respectively. The serum half-life was 4 h after the oral doses and 2.1 h after the intravenous dose. After the oral doses, the amounts excreted in urine in the active form ranged from 36 to 40% compared to 93% after the intravenous dose. The bioavailability was slightly below 40%. Concentrations in urine covers the usual urinary tract pathogens after oral doses of 2, 3, and 4 g. PMID- 8370322 TI - Antimicrobial activity of new antibiotics against bacterial isolates from a community hospital. AB - In this study, the antimicrobial activity of several new antibiotics was evaluated using microdilution antimicrobial susceptibility testing against 220 clinically significant isolates obtained from a community hospital. The following antibiotics were studied: loracarbef, cefixime, cefpirome, desacetylcefotaxime, cefpodoxime, cefmetazole, cefepime, cefprozil and fleroxacin. The synergy of two particular drug combinations was evaluated using cefpirome/desacetylcefotaxime and cefpodoxime/desacetylcefotaxime. Cefpirome was clearly the most active antibiotic: 88% of the isolates tested were found to be susceptible. Specifically, this included 89% of enterococci, 84% of Pseudomonas aeruginosa, and 33% of Pseudomonas cepacia. All of the antibiotics tested demonstrated excellent activity against isolates of Escherichia coli and Klebsiella, Proteus and Salmonella species. For the other antimicrobials, 57, 50, 64, 65, 76, 74, and 64% of the isolates were sensitive to loracarbef, cefixime, cefmetazole, cefprozil, fleroxacin, desacetylcefotaxime, and cefpodoxime, respectively. Among the gram-positive species, 88 and 92.5% of the isolates were sensitive to cefprozil and cefpirome, respectively. Cefepime and fleroxacin demonstrated the highest gram-negative activity with 85 and 89%, respectively, of the isolates being sensitive. The results of this study highlighted cefepime and cefpirome, which showed high overall in vitro activity against 79 and 88%, respectively, of the isolates tested. PMID- 8370323 TI - Taurolidine: in vitro activity against multiple-antibiotic-resistant, nosocomially significant clinical isolates of Staphylococcus aureus, Enterococcus faecium, and diverse Enterobacteriaceae. AB - Taurolidine at < or = 1,250 micrograms/ml killed all 37 isolates of multiple antibiotic-resistant Staphylococcus aureus (n = 9), Enterococcus faecium (n = 17), and Enterobacteriaceae (n = 11). Time-kill experiments disclosed that bovine serum (65% v/v) only marginally retarded the bactericidal activity of 2,000 and 1,000 micrograms/ml of taurolidine against the various strains. Taurolidine at 2,000 micrograms/ml did not antagonize the bactericidal activity of 50% (v/v) fresh human serum against promptly and delayed serum-sensitive test strains of Escherichia coli and Serratia marcescens. In the presence of 65% (v/v) of fresh defibrinated human blood from two donors, however, the bactericidal activity of this antimicrobial compound was delayed, i.e., manifested only following extended (overnight) incubation, against staphylococcal and enterococcal isolates, though less so in the case of Enterobacteriaceae. Taurolidine at 2,000 micrograms/ml killed ingested, i.e., intraphagocytic bacteria of human-serum-resistant S. marcescens strains CDC 06:H3 and P016:H-. PMID- 8370324 TI - Efficacy of ceftizoxime in the treatment of incubating syphilis in rabbits. AB - While ceftizoxime given as a single intramuscular shot cures uncomplicated gonorrhoea in almost every case, its efficacy against Treponema pallidum in cases of concomitant incubating syphilis is less clear. To analyse this question, the rabbit orchitis model was used. After initial experiments defining appropriate inocula and doses, ceftizoxime was compared to penicillin G with its well-known activity against the organism in vitro and in vivo. According to the final experiment, ceftizoxime applied in doses corresponding to the ones used in humans for uncomplicated gonorrhoea cures rabbit orchitis due to T. pallidum about as effectively as penicillin. Hence there seems to be no need to refrain from using the third-generation cephalosporin ceftizoxime to cure gonorrhoea for fear of masking concomitant syphilis. PMID- 8370325 TI - In vitro experiments on catheter-related infections due to gram-negative rods. AB - Although many complications may arise with the use of central venous catheters, catheter-related bacteremia is considered to be the most serious complication. Microflora on the patient's skin (coagulase-negative staphylococci, Staphylococcus aureus) is thought to represent the major source of microorganisms causing catheter-related infections. Gram-negative rods are increasingly observed as causative agents. We therefore performed an in vitro study to elucidate the pathogenesis of polymer-associated infections caused by enterobacteriaceae and nonfermenters and to study the resistance of polymer surface-grown gram-negative rods against antibiotics. Using a modification of the semiquantitative method for culturing vascular cannulas on solid media described by Maki et al., we studied the adherence of various gram-negative rods to 1-cm segments of silastic catheters, a material used for Port-A-Cath-systems. Organisms were obtained from the American Type Culture Collection (Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa, Enterobacter cloacae). All organisms but Klebsiella showed extensive irreversible adherence. Production of an extracellular slime substance was observed only with antimicrobially treated Pseudomonas. After 'infection', the silastic catheter segments were treated with various antimicrobial agents. The following antibiotics were used either individually or in combination: cefotaxime, ciprofloxacin, imipenem, fosfomycin and gentamicin. Despite the fact that the antibiotic concentrations used were many times greater than the respective MICs of the various antibiotics, none of the antibiotics tested succeeded in eliminating the organisms. E. coli was found to be the most susceptible organism. These in vitro data substantiate our clinical impression that it is hardly possible to successfully eliminate the colonization of central venous catheters with gram-negative rods by using the antimicrobial agents employed here. PMID- 8370326 TI - Comparative efficacy of ceftriaxone in experimental infections involving Bacteroides fragilis and Escherichia coli. AB - The in vivo activity of ceftriaxone was examined in an experimentally induced subcutaneous infection involving Bacteroides fragilis and Escherichia coli. Mice were challenged with 1 of 10 strains of B. fragilis or E. coli, or a dual combination of the two species. The efficacy was measured by a reduction in the count of viable organisms when antimicrobial treatment was initiated 1 h after challenge and continued for 5 days. Ceftriaxone exhibited impressive activity against E. coli but showed poor in vivo activity versus B. fragilis. The antimicrobial activity of ceftriaxone was influenced by the microbial interaction in our dual-isolate model. Pharmacokinetic studies showed that ceftriaxone penetrated into abscesses and achieved peak levels of about 40% of the peak serum levels. However, in abscesses infected with B. fragilis nearly all biological activity of ceftriaxone was lost. PMID- 8370327 TI - Treatment of renal cell carcinoma with escalating doses of alpha-interferon. AB - Forty-one patients with advanced renal cell cancer started treatment with recombinant alpha-interferon intramuscularly, beginning at a dose of 5 x 10(6) U x 3/week, progressively increasing doses every week, from 5 x 10(6) U x 3/week to 10 x 10(6) U x 3/week, to the highest dose of 15 x 10(6) U x 3/week. No complete response was achieved, partial response was achieved in 6 (13%) patients with a median duration of 45.2 (13-134) weeks. The majority of side effects from interferon treatment evaluated according to WHO classification were seen during the first 2 months and they were fever (after interferon administration) in 95% patients, chills (51%), flu like syndrome (65%), fatigue (87%), anorexia (80%), worsening in performance status (56%), nausea and vomiting (19%), weight loss (> 10% during therapy) (26%), leukopenia (14%), anemia (75%), neurological symptoms (43%), psychological symptoms (19%) and dyspnea (9%). The results are similar to other studies and toxicity was only moderate. PMID- 8370328 TI - The world's longest user of an insulin pump? PMID- 8370329 TI - Institutionalization of diabetes care and education programs: a tale of two cities. PMID- 8370330 TI - Partners provide adaptive education for people who are visually impaired. PMID- 8370331 TI - The relationship between diabetes-related attitudes and patients' self-reported adherence. AB - This study involved 1202 patients who were placed into low adherence or high adherence groups based on their answers to questionnaires. The attitudes of each group were compared for a variety of adherence behaviors. Patients who reported high levels of adherence tended to have attitudes more in accord with diabetes experts. Members of the high adherence group strongly supported the need for special training for health care professionals who treat diabetes, favored team care, accepted the importance of patient compliance, acknowledged the seriousness of non-insulin-dependent diabetes mellitus (NIDDM), and recognized the relationship between glucose control and complications. Differences in attitudes between high- and low adherence groups were more prevalent for difficult adherence areas, eg, diet and exercise, than for easy adherence areas, eg, carrying sweets or diabetic identification. An understanding of patients' attitudes can help diabetes educators and patients develop realistic and relevant self-care plans. PMID- 8370332 TI - Diabetes and job performance: an empirical investigation. AB - There are approximately 11 million people in the United States with diabetes, and the numbers are increasing by 6% annually. Still, the relationship between diabetes and job performance remains unclear and marked by bias. To help clarify this relationship, a multicriterion job-performance rating scale was developed to rate task behaviors, interpersonal behaviors, down-time behaviors, and hazardous behaviors. A volunteer sample of 53 subjects was selected from people with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). All subjects were rated individually by a supervisor, who also rated the norm for the work group. The norm rating was used to determine a norm referenced control group. The subjects were rated better than the norm in all categories and on all criteria: composite job performance (P < .001), task behaviors (P < .01), interpersonal behaviors (P < .01), down-time behaviors (P < .05), and hazardous behaviors (P < .001). PMID- 8370333 TI - The knowledge and practices of registered nurse, certified diabetes educators: teaching elderly clients about exercise. AB - This study identified the knowledge base and practices of Registered Nurse, Certified Diabetes Educators (RN, CDEs) regarding their exercise teaching programs for elderly clients who have non-insulin-dependent diabetes mellitus (NIDDM). The random sample of 197 AADE members surveyed by questionnaire was a highly educated and experienced group. RN, CDEs who worked 30 or more hours per week in diabetes education or attended four or more continuing education (CE) programs per year had significantly more comprehensive exercise teaching program designs and instructional techniques to enhance elderly NIDDM clients' learning (P < .05). However, many CDEs do not teach their elderly clients about exercise due to lack of resources, lack of specific knowledge to prescribe exercise,and negative stereotypes of elderly clients' ability to exercise. Greater availability of educational programs for CDEs to explore curriculum development, program planning, evaluation, and exercise prescription for elderly clients with multisystem disease is recommended. PMID- 8370334 TI - A review of the effects of resistance training for individuals with diabetes mellitus. AB - Although the effectiveness of exercise as a treatment modality for the management of diabetes mellitus has long been recognized, a vital component of the exercise prescription has been overlooked. In addition to endurance training, resistance training may provide physiologic benefits to the individual with diabetes that, in some cases, may equal or exceed those gained through aerobic training. These benefits may include improved blood lipid profiles, increased absolute left ventricular wall contractility, decreased resting blood pressure, improved insulin sensitivity and glucose tolerance, improved glycemic control, improved muscular strength and endurance, and increased bone and connective tissue strength. By utilizing a combination of aerobic and resistance training, the individual with diabetes experiences a more comprehensive exercise program that can improve most areas of health and physical fitness. In addition, having a greater number of exercise modality options may enhance exercise compliance. PMID- 8370335 TI - Non-insulin-dependent diabetes and obesity in the black and Hispanic population: culturally sensitive management. AB - The prevalence of diabetes is considerably higher among ethnic minorities, particularly black and Hispanic Americans, than in the nonminority white population. Obesity, a significant risk factor for non-insulin-dependent diabetes mellitus (NIDDM), also is more common in these ethnic groups. Because the combined effects of obesity and NIDDM can lead to potentially serious complications, overweight patients with NIDDM must be treated aggressively. However, effective treatment of these ethnic groups requires a sensitivity to and recognition of their unique cultural values. Diabetes educators and health care providers need to take into account specific ethnic beliefs, customs, food patterns, and health care practices, with the goal of incorporating these cultural factors into a practical and beneficial treatment regimen. PMID- 8370336 TI - Teaching foot care creatively and successfully. PMID- 8370337 TI - Higher levels of nicotine in arterial than in venous blood after cigarette smoking. AB - We examined differences between arterial and venous concentrations of nicotine in human subjects. Shortly after smoking a cigarette, levels of nicotine in arterial plasma were more than double those in venous plasma. The time course of the rise in arterial nicotine levels and the magnitude of the arteriovenous difference varied considerably among subjects. For some subjects, arterial nicotine concentrations after one cigarette were similar to venous concentrations typically observed after 20 cigarettes and were nearly 10 times greater than venous concentrations. Our findings have implications for understanding the high degree of addictiveness and cardiovascular toxicity of smoked forms of drugs. PMID- 8370338 TI - Effects of GBR 12909 and cocaine on cocaine-maintained behavior in rhesus monkeys. AB - The reinforcing effect of the high affinity dopamine reuptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl)-4(3- phenylpropyl)piperazine) was compared with that of cocaine, and the effects of both GBR 12909 and cocaine pretreatments were evaluated on behaviour maintained by cocaine in rhesus monkeys. Increasing dose per injection of intravenously-delivered GBR 12909 or cocaine led to increased rates of lever-press responding. Maximum cocaine maintained rates were higher and occurred at a smaller dose than maximum rates of GBR 12909-maintained responding. Presession intravenous administration of either GBR 12909 or cocaine (0.32, 1.0 or 3.2 mg/kg) resulted in dose-dependent decreases in rates of cocaine-maintained responding when high doses of cocaine, which engendered high response rates, were available early in the session. Under these conditions, the decrease in response rates was associated primarily with decreases in running rate rather than with a lengthening in post-reinforcement pause times. The decreases in running rate produced by both cocaine and GBR 12909 probably reflect an unconditioned rate-disruptive effect of these drugs on cocaine-reinforced responding rather than a reduction in the reinforcing efficacy of cocaine. PMID- 8370339 TI - A case-control study of driving-while-impaired offenders. AB - A case control approach was used to identify variables associated with driving while impaired (DWI). Data utilized for this study were obtained from interviews with individuals in a representative sample of 9943 Canadians. Individuals convicted for DWI were matched with control subjects (i.e. no DWI convictions) by gender, age, province of residence, education, income, and recent drinking behaviour. During the matching process, 39 current abstainers were found among the DWI offenders and were treated as a separate group for statistical purposes. Three groups were compared: 78 DWI cases, 78 matched controls, and 39 DWI current abstainers. Statistical analyses were used to detect significant differences among these three groups for 81 variables within the following categories: (a) attitudes, knowledge and behaviour related to drinking and driving; (b) driving behaviour; (c) drinking behaviour and drug use; (d) social issues; and (e) attitudes towards different policy approaches to reducing drinking and driving. DWI cases were significantly different from control subjects for only 10 variables. A high proportion of differences found between these two groups related to attitudes regarding drinking and driving behaviour. For example, DWI cases were more likely than controls to believe that some people drive better after drinking, that it takes more alcohol to be legally impaired, and that there is an excuse for DWI. DWI cases were more likely to drink due to sadness or loneliness, and reported higher cannabis use over previous years. Little evidence was found to support the hypothesis that DWI offenders are less likely to perceive deterrents to DWI. However, evidence does support the notion that many DWI offenders do not believe that they have a drinking problem. Implications of the findings are discussed. PMID- 8370340 TI - Injecting drug users and HIV/AIDS: risk behaviours and risk perception. AB - This paper reports on the incidence of risk taking behaviours, and the relationship between risk perception and risk behaviours in a sample of 1245 Sydney injecting drug users (IDUs). Almost all respondents reported engaging in behaviours that placed them at risk of HIV infection: 32.9% through unsafe injecting, 84.4% because of unsafe sexual behaviour and 89.2% because of either injecting or sexual behaviour. Injecting and sexual behaviour were poorly correlated. This study also found that risk perception is unrelated to injecting or sexual behaviours, previous history of sexually transmitted diseases, a range of demographic characteristics including age and gender, and the number of times tested for HIV. Social policy and prevention programs should aim to change unsafe injecting and sexual behaviours directly, rather than attempting to achieve change indirectly by changing risk perception. PMID- 8370341 TI - The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. AB - Two surveys of 12 months duration were undertaken on opioid users presenting to the Wellington Alcohol and Drug Centre before and after the introduction of a combination buprenorphine 0.2 mg-naloxone 0.17 mg tablet (Bu-Nx), which was launched in 1991 in the hope of reducing intravenous misuse. There was considerable intravenous (i.v.) misuse of buprenorphine 0.2 mg tablets (Bu) in 1990 with self-reports of misuse in 81% of the patients over the 4 weeks prior to presentation, and 65% of the patients had buprenorphine in their urine. In the repeat survey 57% reported misuse of the Bu-Nx combination over the previous 4 weeks, and 43% had buprenorphine +/- naloxone detected in their urine. There was a reduction in the street price of Bu-Nx. One-third of the patients who used Bu Nx i.v. reported instances of withdrawal symptoms, and subjectively the drug was less attractive to misusers. The combination product may have less misuse potential than buprenorphine alone, but it remains a preparation, in the dosages employed, that is intravenously misused. PMID- 8370342 TI - Inhibition of non-enzymatic lipid peroxidation by 'Essentiale' a drug enriched in phosphatidylcholine in ethanol-induced liver injury. AB - The effect of 'Essentiale'--a drug, now clinically listed in European countries in the treatment of liver diseases was examined in ethanol-induced liver injury in rats (free access to a 20% ethanol solution for 3 months). The antioxidant enzymes, SOD (superoxide dismutase), CAT (catalase), GSH-R (glutathione reductase), non-protein and total SH groups as well as TBA-rs contents were investigated. Following treatment, we found beneficial effects in SOD and CAT activities. The above enzyme activities were restored after a 3-month drug administration. Furthermore, 'Essentiale' treatment normalized TBA-rs levels in the liver. These effects have been briefly discussed. PMID- 8370343 TI - Factors affecting neutrophil transit during acute pulmonary inflammation: minireview. AB - Recent studies confirm data that for over a century have suggested that the lungs are an important source of noncirculating neutrophils. Many factors control how neutrophils pass through the normal lungs, including the unique and complex structure of the pulmonary capillary bed, local hemodynamic factors, neutrophil deformability, and neutrophil-endothelial interactions. Alterations in these factors are likely to influence neutrophil traffic in the lungs in disease processes where neutrophil-induced lung injury has been implicated. In recent years experimental approaches using in vitro techniques have been used to study neutrophil function. Such studies, together with in vivo studies in whole animals and to a limited extent in humans, will help to elucidate the important mechanisms in neutrophil sequestration in the acute and chronically inflamed lung. Novel avenues of therapeutic intervention in neutrophil traffic through the lungs may then be possible. However, whether interference with this cell, which forms a major defense mechanism in the lungs, is advisable, remains a matter for debate. PMID- 8370344 TI - Effect of pentamidine on cytokine (IL-1 beta, TNF alpha, IL-6) production by human alveolar macrophages in vitro. AB - Pentamidine (Pe) is an aromatic diamidine drug used clinically to treat Pneumocystis carinii pneumonia by aerosol inhalation. Nothing has been reported about the effects of this drug on human alveolar macrophage (AM) properties. In this study AM were exposed in vitro to various concentrations of Pe (10(-4)-10( 6) M) alone or in combination with bacterial endotoxin (LPS). Supernatants were collected at 3, 6, and 24 h and assayed for secreted IL-1 beta, IL-6, and TNF alpha. While the drug did not induce release of these cytokines, LPS-induced secretion of all three cytokines was inhibited by Pe in a dose-dependent manner. At the most effective Pe dose, 10(-5) M, AM viability (as determined by trypan blue dye exclusion) was reduced by 14% at 24 h, while no effect on viability was seen at lower concentrations. mRNA expression of all three cytokines was examined by PCR and Northern analysis to establish if the decrease in cytokine secretion was determined on a pre- or post-translational level. Reduced steady-state mRNA levels were found as early as 3 h after LPS stimulation, with Pe concentrations corresponding to those that decreased cytokine secretion. At the later time points, Pe also inhibited beta-actin, ornithine decarboxylase, and GAPDH mRNA expression, indicating that pentamidine had a general toxic effect on mRNA transcription in the macrophages. It is concluded that Pe, at pharmaceutically relevant concentrations and with apparent low cytotoxicity as determined by dye uptake, nonspecifically inhibits cytokine production by a toxic effect on transcriptional events. PMID- 8370345 TI - Lung clearance in Long-Evans rats after inhalation of porous, monodisperse cobalt oxide particles. AB - Lung clearance of a well-defined uniform and respirable material was conducted to aid in the development of models used to relate inhalation of inorganic hazardous particles to organ doses and bioassay measurements, and in particular to aid in the extrapolation of animal data to humans. In the present study, lung clearance was investigated in Long-Evans rats using monodisperse, porous, 0.8- and 1.7 microns-diameter cobalt oxide (Co3O4) test particles. An advanced inhalation technique for rats using endotracheal intubation yielded exclusive particle deposition in the pulmonary region without external pelt contamination, thus allowing for clearance studies starting directly after inhalation. The kinetics of lung clearance was distinguished between the two dominant clearance mechanisms of mechanical particle transport to the larynx and translocation of dissolved particle material to blood. A particle fraction of about 40% was cleared by short term particle transport to the larynx, both the long-term particle transport rate and the translocation rate of dissolved particle material given as fractional rates of the retained particle mass in the lungs were not constant with time. The former declined from 0.03 to 0.004 d-1 during 6 months after inhalation. The latter depended on the specific surface area of the porous particles and increased with time from 0.08 and 0.04 d-1 for 0.8- and 1.7-microns particles, respectively. The results obtained were compared to previously reported data obtained from Fischer-344 rats and HMT rats. These were part of a previously reported interspecies comparison of lung clearance followed in seven species, including humans, and using the same batches of Co3O4 test particles. Long-term lung retention was similar in Long-Evans rats and HMT rats but decreased faster for both particle sizes than in Fischer-344 rats, as a result of a significantly faster translocation of dissolved material from the test particles to blood. Mechanical particle transport to the larynx was comparable in all three species. PMID- 8370346 TI - Comparison of antioxidant substances in bronchoalveolar lavage cells and fluid from humans, guinea pigs, and rats. AB - Antioxidants located in the lining layer of the respiratory tract may be important in determining sensitivity of lung tissues to inhaled pollutants. This study addressed species differences in the amounts of ascorbic acid (AH2), glutathione (GSH), uric acid (UA), and alpha-tocopherol (AT) in bronchoalveolar lavage (BAL) fluid and cells of humans, guinea pigs, and rats. Protein and lipid phosphorus (lipid P) were used as normalizing factors. More than 90% of the lavageable AH2, UA, GSH, protein, and lipid P was present in the extracellular fraction of BAL in rats and guinea pigs, while over 95% of the lavageable AT was located in the BAL cells. BAL fluid AH2/protein in rats was 7- to 9-fold higher than in humans and guinea pigs. However, human BAL fluid had 2- to 8-fold higher UA/protein, GSH/protein, and AT/protein ratios than rats and guinea pigs. In BAL cells, rats had higher AH2/protein and AT/protein ratios than guinea pigs and humans, and both rats and guinea pigs had higher GSH and AT/protein ratios than humans. Individual variability among humans in the BAL fluid and cellular antioxidants was generally greater than in the laboratory animals. These data demonstrate that some large species differences exist in BAL fluid and cellular antioxidants which could affect susceptibility to oxidant pollutants. PMID- 8370347 TI - Conservation analysis of rat and human SP-A gene identifies 5' flanking sequences of rat SP-A that bind rat lung nuclear proteins. AB - As an initial step toward understanding regulation of tissue-specific expression of SP-A, 5' flanking sequences of the rat SP-A gene and human SP-A I gene were cloned, sequenced, and compared using dot matrix analysis. Two regions were identified, each with a considerable degree of homology between the two species. One region was proximal to the TATAA box, at position -225/-17 in rats and -226/ 36 in humans, and the other at position -1115/-1026 in rats and -938/-851 in humans. Studies in rats revealed the specific binding of rat lung nuclear proteins to each of the conserved 5' flanking regions identified in rat SP-A. Binding studies using the rat proximal (rPPS) or distal (rDPS) promoter segments, or overlapping fragments of these segments, with rat nuclear extracts detected the presence of a number (1-4) of lung-specific DNA/protein complexes. When nuclear proteins from liver, a nonexpressing tissue, were used the binding profile of certain nuclear proteins differed from that of the lung. These studies, taken together, suggest that sequences within identified conserved DNA segments in the 5' flanking region of the rat SP-A gene contribute to its tissue specific expression in rats. PMID- 8370348 TI - Stretch-induced growth-promoting activities stimulate fetal rat lung epithelial cell proliferation. AB - There is increasing evidence to suggest that fetal lung growth requires normal fetal breathing movements. To study this process in vitro, the effect of mechanical stretch on proliferation of fetal rat lung cells maintained in organotypic cultures was examined. In previous studies it has been demonstrated that DNA synthesis and cell division are stimulated by stretch. To determine whether stretched cells release soluble growth factors into their culture medium, conditioned media (CMs) were collected after static culture or culture while stretched. At a 10% dilution (v/v), CM from stretched cells (S-CM) increased [3H]thymidine incorporation into DNA of mixed fetal rat lung cells by 60%, compared to CM from nonstretched cells (C-CM) (p < .01). S-CM increased [3H]thymidine incorporation of fetal lung epithelial cells by 3 to 4-fold (p < .01) and increased cell number by 11.9% (p < .05), but had no effect on fetal lung fibroblast growth. Addition of either PDGF-BB (20 ng/mL), IGF-I (25 ng/mL), or EGF (50 ng/mL) to C-CM, did not mimic the effect of S-CM on epithelial cell DNA synthesis. The stimulatory activity of S-CM on epithelial cell proliferation was heat-, acid- and trypsin-sensitive. It is concluded that organotypic fetal lung cell cultures respond to stretch by elaborating growth-promoting factors which stimulate fetal rat lung epithelial cell, but not fibroblast, proliferation. PMID- 8370349 TI - Effects of valproate and E-2-en-valproate on functional and morphological parameters of rat liver. II. Influence of phenobarbital comedication. AB - The effect of phenobarbital on the potential hepatotoxicity of E-2-en-valproate (E-2-en-VPA; trans-2-en-VPA) and VPA was studied in young male Sprague-Dawley rats. E-2-en-VPA and VPA were administered daily at 750 mg/kg i.p. (divided into three doses a day) for 7 consecutive days. Phenobarbital was coadministered i.p. once daily at 100 mg/kg for 2 days, followed by daily injections of 50 mg/kg for the subsequent days of the treatment period. Additional groups of rats were treated with phenobarbital alone or received once daily administration of 4-en VPA (100 mg/kg), a potentially hepatotoxic metabolite of VPA. Clinical chemistry data were studied before and after the period of treatment. Furthermore, drug and metabolite levels were analyzed by gas chromatography-mass spectrometry. Treatment with VPA and phenobarbital resulted in deaths and histopathological liver alterations, such as marked microvesicular steatosis and degenerative lesions, whereas no death and hepatotoxicity occurred in rats treated with E-2-en VPA and phenobarbital. Furthermore, hyperammonemia was recorded in VPA- but not E 2-en-VPA-treated rats. In comparison to treatment with VPA or E-2-en-VPA alone, combined treatment with phenobarbital markedly reduced plasma levels of the parent drugs and metabolites originating from beta-oxidation, but, in case of VPA, increased metabolites originating from omega-oxidation. Plasma levels of 4 en-VPA were increased by phenobarbital in VPA-treated rats, but 4-en-VPA was not detectable in rats treated with E-2-en-VPA. The most severe alterations in functional and morphological liver parameters were found in rats treated with 4 en-VPA. In these animals, the extent of steatosis was significantly correlated with plasma levels of 4-en-VPA, but not its major metabolite 2,4-dien-VPA. Plasma levels of 4-en-VPA or its major metabolite 2,4-dien-VPA in rats without steatosis were markedly higher than levels of these compounds in VPA-treated rats with steatosis, suggesting that 4-en-VPA and 2,4-dien-VPA are not critically involved in the hepatotoxic effects of VPA. The data substantiate that E-2-en-VPA is less hepatotoxic than VPA and may thus offer advantages for antiepileptic therapy. PMID- 8370350 TI - Reciprocal positive transfer between kindling of audiogenic seizures and electrical kindling of inferior colliculus. AB - The behavioral and EEG concomitants of kindling produced by daily electrical stimulation of the inferior colliculus have been recorded in three series of Wistar rats: (1) non epileptic controls (NE), (2) rats susceptible to audiogenic seizures (AS), (3) acoustically susceptible rats with prior kindling of audiogenic seizures by repeated sound exposure (KAS). Repeated collicular stimulation produced behavioral and EEG changes which were similar in the AS and the NE rats. The tonic seizure without cortical discharges elicited by the first stimulation progressively changed into tonic-clonic seizures with sustained cortical EEG discharges after more than 20 stimulations. In the KAS group, the electrical collicular kindling was clearly accelerated: kindled tonic-clonic seizures and their EEG discharges already occurred after one to five electrical stimulations. Similarly, after completion of electrical collicular kindling in AS, sound stimulations immediately induced characteristic kindled audiogenic seizures. The immediate reciprocal positive transfer observed between kindling of audiogenic seizures and kindling of seizures induced by electrical stimulation of the inferior colliculus suggests that kindling of these two brain-stem seizures involves similar structures and mechanisms. PMID- 8370351 TI - The anticonvulsant activity of D-cycloserine is specific for tonic convulsions. AB - D-Cycloserine has been shown to exert anticonvulsant activity in maximal electroshock seizures. The purpose of the present study was to evaluate the spectrum of D-cycloserine anticonvulsant activity using other experimental models of epilepsy. D-Cycloserine induced a dose-related decrease in the incidence of tonic convulsions induced by 120 mg/kg of pentylenetetrazol. The ED50 of D cycloserine for the inhibition of the tonic convulsions was 109 mg/kg. The anticonvulsant activity was specific for the D-isomer at L-cycloserine (400 mg/kg) had no effect on the tonic convulsions. D-Cycloserine had no effect on the pentylenetetrazol-induced clonic convulsions induced by either 70 or 120 mg/kg pentylenetetrazol, electrically induced nonkindled hippocampal seizures or kindled amygdala seizures. D-Cycloserine had no effect on strychnine-induced tonic convulsions. These results indicate that D-cycloserine is inactive against clonic convulsions and may be active only against tonic convulsions mediated by brainstem sites. PMID- 8370352 TI - Conventional and rapid stimulation evoked potential changes in patients with status epilepticus. AB - We utilized somatosensory evoked potentials to evaluate 33 patients with status epilepticus who did not have focal neurological etiologies. Eighteen percent of the patients had conventional stimulation evoked potential abnormalities at or above the P14 lemniscal level. Evoked potential abnormalities in this population showed a statistically significant correlation with a poor outcome including patients that died or required dependent care following hospital discharge. Rapid stimulation somatosensory evoked potential testing is a new technology which may be useful to detect more subtle central nervous system injury and was successfully utilized in the acute setting. Combined conventional and rapid stimulation evoked potentials demonstrated that 30% of these patients had abnormal findings. The results demonstrate that a significant percentage of status epilepticus patients have somatosensory evoked potential abnormalities and suggest that conventional and rapid stimulation somatosensory evoked potentials may be useful predictive indicators for predicting outcome and mortality in this condition. PMID- 8370353 TI - Memory complaints in epilepsy: correlations with cognitive performance and neuroticism. AB - Subjective memory functioning was assessed by a questionnaire in 102 patients with epilepsy. Factor analysis of their responses yielded five factors: (1) Absentmindedness, (2) Retrieval, (3) Memory for Semantic Structures, (4) Childhood Memories and (5) Rote Memory. Scales representing the factors were constructed. On all scales, patients (n = 71) who had been specifically referred for an evaluation of subjective memory problems showed moderate to large differences from normal Controls (n = 111) in complaint scores, indicating adequate sensitivity of the scales to clinically significant complaint levels. By contrast, candidates for epilepsy surgery (n = 31) resembled the Controls in their perceived memory status, showing a moderately elevated complaint level on only one of the factor based scales. Relationships of subjective memory difficulties to performance on objective tests of memory and other relevant cognitive functions as well as neuroticism were examined. The two epilepsy groups were fairly similar in their test performance, but differed markedly in their subjective memory problems. Also, correlational analysis revealed only a single weak correlation between cognitive tests and subjective memory ratings. The present findings indicate that there is no simple relationship between subjective evaluations of memory and test performance. Patients' memory complaints do not accurately predict disturbances that can be measured on standard neuropsychological tests. Such complaints may be related more to neuroticism. Also, psychosocial difficulties which may accompany chronic disorders in general may have to be invoked to account for memory complaints in people with epilepsy. The epilepsy itself does not appear to be a critical factor in producing memory complaints. PMID- 8370354 TI - Physiological correlates of abnormal behaviors in magnesium-deficient rats. AB - In order to elucidate the mechanism of behavioral alterations in magnesium deficient rats, changes in the electroencephalogram (EEG) and electrocardiogram (ECG) were studied during auditory stimulation and correlated with the behavioral alterations. Weanling rats were fed either a Mg-deficient diet or a control synthetic diet for 2-3 weeks before the experiment. EEGs were recorded from the hippocampus and the sensorimotor and auditory cortices, and ECGs with a telemetry system. White noise with an intensity of 100 dB was given continuously to induce behavioral changes. The Mg-deficient rats developed consistent and graded behavioral changes in response to the stimulation, showing running-jumping behavior (stage 1), followed by tonic limb convulsion (stage 2) and finally by falling down on the floor (stage 3). The EEGs also showed consistent changes with spike activity, initiating in the hippocampus (stage 2) and then spreading to the neocortices bilaterally (stage 3). These findings indicate that the behavioral changes induced by auditory stimulation in the Mg-deficient rats are due to seizures arising in deeper brain structures, particularly in the limbic system, and projecting secondarily to the neocortices. The ECG changes, mainly consisting of marked bradyarrhythmia, occurred as early as the appearance of the EEG spikes, indicating that they were also related to the seizure. We conclude therefore that Mg deficiency in rats causes increased excitability of the central nervous system, resulting in seizures possibly originated in the limbic system, later developing secondary generalization, and also causing cardiac dysfunctions. PMID- 8370355 TI - Epileptogenic spikes and seizures but not high voltage spindles are induced by local frontal cortical application of gamma-hydroxybutyrate. AB - Combining the methods of microdialysis and EEG recording, we have examined the effect of unilaterally, intracortically applied gamma-hydroxybutyrate (GHB) on frontal cortical EEG activity in freely moving rats. GHB, a natural endogenous GABA metabolite, is known to induce rhythmic spike and wave activity, resembling generalized petit mal epilepsy. Without GHB, spontaneous high voltage spindles (HVS, 6-9 Hz) were observed during awake and immobile behavior in most of the animals (HVS rats), while others never had any HVS. In those both groups of animals intracortical application of GHB induced epileptogenic spikes (< 0.5 Hz) behaviorally accompanied by occasional myoclonic jerks and epileptic discharges (< 2 Hz) with behavioral convulsions and contraversive movements towards the left hindlimb (seizures) but did not induce HVS or spike and waves, as reported after systemic application. In the group of rats with spontaneous occurring HVS the amplitude of the HVS on the side of the microdialysis probe was suppressed by GHB and GHB-induced spikes invading the contralateral cortex frequently triggered and terminated local HVS. The results point to different neural mechanisms for the generation of HVS and spikes and epileptic discharges (seizures) induced after local intracortical application of GHB. PMID- 8370356 TI - Left ventricular dysfunction following transient ischaemia induced by transluminal coronary angioplasty. Beneficial effects of calcium antagonists against post-ischaemic myocardial stunning. AB - Acute and severe ischaemia is followed by depression of myocardial contractility during reperfusion; return to full recovery might take a long time. This phenomenon, termed myocardial stunning, has been extensively demonstrated in experimental studies and in different clinical settings. The beneficial effects of calcium antagonists in preventing post-ischaemic myocardial stunning have been tested in experimental studies, showing that when administered before or during ischaemia, they inhibit post-ischaemic myocardial dysfunction. The present study was undertaken to verify the possible occurrence of myocardial stunning following transient ischaemia induced by coronary angioplasty. The aim was also to evaluate the possible protective effects of calcium antagonists (nisoldipine) and nitrates against myocardial stunning in patients with coronary artery disease undergoing routine coronary angioplasty (PCTA) with prolonged inflation. The study included 25 patients, aged between 40 and 69 years, with exercise-induced angina and single vessel disease. The stenosis was severe (80% to subtotal occlusion), localized on the left anterior descending artery, but without collaterals at coronary angiogram. All patients had normal left ventricular (LV) overall function and normal systolic thickening of the anterior wall supplied by the diseased artery. Our data suggest that post-ischaemic myocardial stunning is not only an experimental curiosity, but that it does occur in different clinical settings. Calcium antagonists (i.e. nisoldipine), when added before or during ischaemia, seem to prevent myocardial stunning. These findings confer a potential role to these agents in the treatment of post-ischaemic myocardial dysfunction. PMID- 8370357 TI - Effect of transient ischaemia on left ventricular function and prognosis. AB - Transient myocardial ischaemia is associated with a rapid reduction in ATP concentration, depletion of glycogen storage, and transient from aerobic to anaerobic metabolism. Repeated ischaemic episodes are associated with structural changes, some of which are transient, while others are permanent. These changes affect myocardial cells, collagen matrix and lead to increased amounts of fibrous tissue, which may impair both systolic and diastolic left ventricular function. Ischaemic changes, whether silent or symptomatic, during exercise testing are independent predictors of worse prognosis beyond the extent of coronary disease. Abolition of exercise-induced ischaemia, either by coronary bypass surgery or by medical therapy is associated with improved outcome. Ischaemic episodes during daily life are independent predictors of future cardiac events beyond results of exercise testing, extent of coronary disease or left ventricular function. Impairment of systolic and diastolic function persists from hours to days after transient ischaemia. Abolition of myocardial ischaemia, either by medical therapy or coronary angioplasty, has been shown to improve both systolic and diastolic function. It seems, therefore, that prevention of ischaemia is fully justified as it preserves the metabolic and functional state of the myocardium and improves prognosis. PMID- 8370358 TI - The hibernating myocardium in ischaemia and congestive heart failure. AB - Hibernating myocardium refers to the presence of persistent myocardial and left ventricular dysfunction at rest due to reduced coronary blood flow that can be partially or completely restored to normal by myocardial revascularization. An increasing amount of data show it is most likely a downgrading of cardiac function so that blood flow and myocardial function are once again in a state of equilibrium. It has been demonstrated to occur in patients with unstable angina, chronic stable angina, acute myocardial infarction and in left ventricular dysfunction and/or congestive heart failure. Salvage of this viable myocardium by successful revascularization improves left ventricular dysfunction and probably also patient survival. Therefore, diagnosis of hibernating myocardium is important because it does not render left ventricular dysfunction a necessary contraindication to revascularization, nor does it leave the patient with chronic heart failure a candidate only for cardiac transplantation. Instead, these patients should have complete revascularization by coronary bypass surgery/percutaneous transluminal coronary angioplasty as soon as possible. PMID- 8370359 TI - Post-ischaemic cardiac dilatation and remodelling: reperfusion injury of the interstitium. AB - Cardiac size and geometry have an important influence on clinical prognosis in heart disease. The cardiac interstitium would appear to play a major role in modulating muscle configuration after ischaemic insults. Ischaemic reperfusion injury of the heart should not be viewed as confined to the myocyte compartment. There are major events occurring in the interstitial compartment which could ultimately determine the long-term configuration and topography of the heart. Thus, permanent plastic changes in cardiac dimensions appear to evolve after initial alterations in the collagen matrix. The physiological, cellular, biochemical, and molecular considerations in the cardiac interstitium are quite different from those of the myocyte compartment. Accordingly, therapeutic interventions to modulate cardiac geometry and remodelling may differ. PMID- 8370360 TI - Cardiac dysfunction and development of heart failure. AB - A major consequence of chronic cardiac dysfunction is chronic overload of contractile myocardium. Various aetiologies, in reaction to this, may induce compensatory mechanisms consisting of excentric (dilatation) and concentric hypertrophy. Chronic left ventricular dysfunction is caused most frequently by myocardial infarction. Left ventricular dilatation and hypertrophy occurs in patients with extensive infarction. Dilatation may at first be compensatory, restoring stroke volume within 4 weeks of the infarct. However, as dilatation progresses, left ventricular ejection fraction and stroke volume deteriorate during exercise and at rest, and finally pulmonary capillary wedge pressure increases and patients become symptomatic 1.5-3 years after the infarct. Major determinants of progressive left ventricular dilatation and deterioration of haemodynamics are a depressed left ventricular ejection fraction, angiographically determined infarct size, stroke volume early (4 days) after myocardial infarction, infarct location (anterior/inferior) and the grade (TIMI) of perfusion of the infarct-associated coronary artery. Chronic loading and unloading may accelerate or decelerate this process. Efficiency and energy reserve (phosphocreatine) of the dilated ventricles is reduced. Further intrinsic changes in surviving myocardium include morphological and functional disturbance of coronary microcirculation. PMID- 8370361 TI - The role of calcium antagonists in the treatment of chronic heart failure. AB - Calcium antagonists have been widely used for the treatment of angina and hypertension. Because of vasodilator and anti-ischaemic properties, calcium antagonists might be expected to bring benefit to patients with heart failure, particularly when the heart failure is due to coronary heart disease. Eight trials of calcium antagonists, fulfilling specific criteria, have been reviewed. The evidence at present does not support the use of calcium antagonists in established heart failure. Some benefit may accure from the use of the newer calcium antagonists but further trials are awaited. Calcium antagonists appear to improve diastolic fraction in patients with coronary heart disease, no overt heart failure but a reduced ejection fraction. PMID- 8370362 TI - Nisoldipine in severe ischaemic left ventricular dysfunction. AB - The use of calcium antagonists in patients with severe dysfunction is controversial because agents like verapamil, diltiazem and nifedipine have been shown to worsen or precipitate congestive heart failure. However, successive improvements in our understanding of the clinical pharmacology of these drugs, of their pharmacokinetics and of their action on several neuro-humoral regulatory mechanisms have led to a continuous improvement of the molecules available. Promising results have been obtained with nisoldipine in patients with ischaemic left ventricular dysfunction (improved exercise tolerance, improved diastolic filling probably related to a relative improvement of chronically ischaemic areas) and other studies are exploring the effects of the combination of nisoldipine with an ACE-inhibitor. Soon, these trials should tell us if there is a real clinical benefit in the use of this agent not only to improve symptoms but also to slow down progression of the ventricular dysfunction. PMID- 8370364 TI - Regional wall motion abnormalities in stunned and hibernating myocardium. AB - The clinical recognition that chronic dysfunctioning myocardial segments may retain viable myocardium has important therapeutic consequences. 'Stunned myocardium' and 'hibernating myocardium' have been proposed to distinguish respectively between post-ischaemic left ventricular dysfunction, a condition which normalizes spontaneously, and persistent wall motion abnormalities due to chronic hypoperfusion. This study examines the possible link between these two conditions. PMID- 8370363 TI - Left ventricular systolic and diastolic dysfunction in the acute phases of myocardial ischaemia and infarction, and in the later phases of recovery. Function follows morphology. AB - Myocardial ischaemia and infarction result in major changes in myocardial function, due to the metabolic and structural cause. The observed morphological changes may be macroscopic--as in clinical myocardial infarction, microscopic--as in severe, prolonged ischaemia, or ultramicroscopic--in regard to the collagen matrix. Recognition of the vulnerability of these structures to the metabolic and mechanical stresses associated with severe ischaemia or infarction allows an understanding of the processes of acute dilatation, late adverse remodelling and compensatory hypertrophy, which determine both systolic and diastolic dysfunction and define the principal clinical complications. Morphology--'Form'--is the primary determinant of function, while metabolic and other factors are secondary, variably dependent on the integrity of structure. PMID- 8370365 TI - Anti-ischaemic actions of potassium channel openers in experimental myocardial ischaemia/reperfusion injury in dogs. AB - The effect of three potassium channel openers, nicorandil, aprikalim, and bimakalim, on experimental myocardial ischaemia/reperfusion injury was examined in barbital-anaesthetized dogs. In a model of reversible injury, administration of nicorandil at a hypotensive dose and aprikalim at a non-hypotensive dose resulted in a reduction in contractile dysfunction during reperfusion ('stunning') following brief coronary artery occlusion (15 min) when the drugs were administered before occlusion. Administration of aprikalim only during reperfusion had no beneficial effect. Pre-treatment with the adenosine triphosphate (ATP)-dependent potassium (KATP) channel antagonist, glibenclamide, blocked completely the beneficial effects of nicorandil and aprikalim, although glibenclamide did not block the haemodynamic effects of nicorandil. In a model of irreversible ischaemia/reperfusion injury (120 min of ischaemia and 30 min of reperfusion) pre-treatment with equihypotensive doses of nicorandil and bimakalim produced marked reductions in myocardial infarct size. Similarly, aprikalim at a non-hypotensive dose reduced myocardial infarct size in dogs subjected to 90 min of ischaemia and 5 h of reperfusion, and the protective effects of aprikalim were antagonized completely by glibenclamide. These results indicate that nicorandil, aprikalim, and bimakalim are protective in two experimental models of ischaemia/reperfusion injury. The mechanism of action of these agents is not completely understood, but it appears to be a result of myocardial KATP channel activation. PMID- 8370366 TI - Coronary haemodynamics and vasodilatory profile of a potassium channel opener in patients with coronary artery disease. AB - Previous studies have indicated that nicorandil reduces both preload and afterload, clearly distinguishing nicorandil from conventional nitrates, whose predominant action is that of preload reduction. In association with the decrease in afterload following nicorandil, the contractile responses during isovolumic contraction and relaxation improved significantly, indicating that nicorandil does not demonstrate negative inotropic actions. Furthermore, despite a marked decrease in mean aortic pressure after nicorandil, coronary sinus blood flow remains unchanged. Therefore, coronary vasodilatation must have taken place, while myocardial oxygen consumption decreased significantly. The vasodilatory action of nicorandil on the epicardial coronary artery has also been demonstrated in our previous study. Nicorandil, at a dose of either 20 or 40 mg, induces a significant increase in coronary artery diameter favourably by acting not only on the non-stenotic but also on the stenotic coronary segments. In our recent study, the effects of intracoronary nicorandil (6 mu.kg-1) and isosorbide dinitrate (2 mg) on the epicardial coronary arteries were investigated in patients undergoing coronary angioplasty. In non-stenotic coronary artery segments, the mean coronary diameter increased significantly after either nicorandil (+12%) or isosorbide dinitrate (+17%). In stenotic segments, however, increase in the diameter of the obstructed segment by 20% after intracoronary nicorandil was much more pronounced when compared to that of 8% after isosorbide dinitrate. There was a significant additional increase of 13% in the diameter of the obstructed segment when nicorandil was administered following isosorbide dinitrate, while no such additional effect was observed when isosorbide dinitrate was given after nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370367 TI - Potassium channels as pharmacological targets in cardiovascular medicine. AB - Potassium channels are membrane receptor sites for various drugs in the field of cardiovascular diseases. These channel proteins are extremely diverse, not only as regards their molecular structure but also as regards their function. Heterogeneous expression of various K+ channel subtypes is an integral part of cell specialization in different tissues. K+ channels interfere with most of the physiological processes of the cardiac muscle, of the vascular smooth muscle and of the endothelial cells. K+ channel blockers are antidiabetic agents but also antiarrhythmic drugs. K+ channel openers are used in the treatment of hypertension and most recently in the treatment of coronary heart disease. In the experimental setting, K+ channel openers afford cytoprotection during ischaemia. This exciting property opens a new field in clinical research. PMID- 8370368 TI - Potassium channel activators in vasospastic angina. AB - Activation of potassium channels induces relaxation of vascular smooth muscle, and experimental studies have demonstrated that potassium channel activators have potent coronary vasodilator properties. In humans, nicorandil, a potassium channel blocker, causes vasodilatation not only in angiographically normal segments but also at sites of dynamic coronary stenosis, where coronary spasm has been provoked by methylergometrine as well as at sites of spontaneous spasm. The efficacy of nicorandil in relieving ergometrine-induced spasm is comparable to that of nifedipine. Oral administration of nicorandil significantly reduces the frequency of anginal episodes in patients with vasospastic angina, and either as monotherapy, or in conjunction with other agents is a novel therapeutic option in patients with vasospastic angina. PMID- 8370369 TI - A potassium channel opener as monotherapy in chronic stable angina pectoris: comparison with placebo. AB - The vasodilating agent nicorandil produces marked coronary artery dilatation by a number of mechanisms including an increase in cyclic guanosine monophosphate, an effect which is common to all organic nitrates, and a novel potassium channel opening effect. In four double-blind, placebo-controlled trials, nicorandil has been shown to produce beneficial haemodynamic effects in patients with stable angina pectoris without significant deleterious effects on pulse rate, the cardiac conducting system, myocardial contractility or myocardial oxygen consumption. Significant improvements in exercise time to onset of angina, exercise time to cardiac ischaemia and total attainable workload have been demonstrated. These effects have been shown to persist for 12 h, allowing it to be used on a twice daily basis. It appears relatively free of important side effects other than a dose-dependent headache, which necessitates discontinuation of treatment in a minority of patients. PMID- 8370370 TI - A double-blind comparison of the long-term efficacy of a potassium channel opener and a calcium antagonist in stable angina pectoris. AB - The efficacies and safety of nicorandil, 20 mg b.d., and diltiazem, 60 mg t.d., in the treatment of stable angina pectoris were compared in a double-blind randomized parallel group study involving 123 patients. The duration of the study was 3 months. Exercise tolerance tests were performed by the patients when on placebo (day 0) and at the end of the study period (day 90). Both groups were comparable at day 0 in terms of demography and cardiovascular status. Nicorandil and diltiazem were both found to decrease the frequency of anginal attacks and the consumption of nitroglycerin tablets (P < 0.01). Maximum exercise capacity, the amount of work that could be performed before reaching ischaemic threshold, and the amount of work required to reach onset of angina were significantly increased for both groups of patients on day 90 compared with day 0 (increase in maximum exercise capacity: nicorandil--6.9 +/- 18.9 kj, diltiazem--9.6 +/- 16.2 kj, P = 0.44 ns; increase in work to ischaemic threshold: nicorandil--9.4 +/- 18.1 kJ, diltiazem--14.7 +/- 15.4 kJ, P = 0.10 ns; increase in work to onset of angina: nicorandil--10.0 +/- 20.1 kJ, diltiazem--11.4 +/- 14.9 kJ, P = 0.68 ns). Differences between the two groups were not significant. The double product of systolic blood pressure x heart rate and peak exercise for both drugs was either unchanged or slightly decreased at ischaemic threshold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370371 TI - A double-blind comparison of a beta-blocker and a potassium channel opener in exercise induced angina. AB - This randomized, double-blind, parallel study compared the anti-anginal effects of nicorandil and atenolol in 37 patients with exercise-induced angina pectoris. At the end of a single-blind placebo period, patients were randomized and received either atenolol 50 mg o.d. or nicorandil 10 mg b.d. for 3 weeks. On the third week, the dosage was increased (nicorandil 20 mg b.d. or atenolol 100 mg o.d.) for the final 3-week period. Treadmill exercise tolerance tests were performed immediately before and 2 h after dosing at the end of the placebo period, and at the end of the third and sixth week of active treatment. Demographic characteristics and exercise performance with placebo were comparable between both treatment groups, and at the end of the treatment periods a significant improvement in exercise time was observed: an increase in the time to peak exercise of 1.33 +/- 0.29 min (mean +/- standard error of the mean) in atenolol-treated patients (P < 0.001), and of 1.47 +/- 0.40 min (P < 0.005) in nicorandil-treated patients. While the anti-anginal activity of the two drugs was comparable, their effects on the rate-pressure product heart rate x systolic blood pressure were clearly different; atenolol induced a decrease at peak exercise, but this parameter was not changed or was slightly increased with nicorandil. One patient with severe three-vessel disease died suddenly after 3 days of treatment with nicorandil 10 mg twice daily. The most frequent adverse effect in both groups was headache, which led to discontinuation of one patient in the atenolol group and of five patients in the nicorandil group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370372 TI - Haemodynamic and clinical effects of an intravenous potassium channel opener--a review. AB - Intravenous nicorandil (4-12 mg) produced a significant decrease in mean arterial blood pressure (-5 to -15%), systemic vascular resistance (-8 to -27%), pulmonary capillary wedge pressure (-15 to -41%) and left ventricular end-diastolic pressure (-8 to -18%) in patients with coronary artery disease, myocardial infarction or congestive heart failure. Cardiac output was significantly increased (+3 to +19%) in most studies. These haemodynamic effects of intravenous nicorandil (4-8 mg) were comparable to those of nitroglycerin (0.3 mg), although a greater decrease in preload was produced by nitroglycerin. Moreover, no significant haemodynamic tolerance developed over a 12 to 24 h period during continuous infusion of nicorandil (2.4 micrograms.kg-.min-1) in patients with heart failure, in contrast to nitroglycerin infusion (0.65 microgram.kg-1 x min 1). Intravenous nicorandil (4-12 mg) was also shown to produce a slightly smaller increase (8-27%) in the diameter of the large coronary arteries compared to that of sublingual nitroglycerin (0.3 mg) (16-32%) and to cause a significant decrease in coronary vascular resistance (-9 to -53%) and a significant increase in coronary sinus flow (+6 to +81%) in patients with coronary artery disease. The efficacy of intravenous nicorandil (2-6 mg.h-1) in unstable angina pectoris has been compared with that of isosorbide dinitrate (2-5 mg.h-1) in a double-blind, multicentre trial. Over a 3 to 9 day period, nicorandil therapy tended to be more effective in abolishing anginal attacks and decreasing nitroglycerin consumption. PMID- 8370373 TI - Safety profile of an anti-anginal agent with potassium channel opening activity: an overview. AB - Safety has been assessed in a total of 1680 subjects who were treated with nicorandil, with 458 patient years of exposure to treatment. Adverse events usually occurred early in the course of treatment. After 30 days of treatment, fewer than 10% of patients reported adverse events. At the recommended doses, the main side effects were limited to headaches. Nearly all episodes of headache were experienced during the first days of nicorandil treatment and were responsible for most of the study withdrawals because of clinical non-acceptability. The incidence can be diminished by a progressive titration. In comparative trials with anti-anginal agents, such as propranolol, diltiazem, nifedipine, ISDN and isosorbide 5 mononitrate, the overall incidence of adverse events was not significantly different between nicorandil and the reference drug. Side-effect distribution was comparable between nicorandil (32%) and diltiazem (30%). Nicorandil can be safely combined with other anti-anginal drugs. Furthermore, due to its favourable pharmacokinetics, nicorandil is less likely to have interactions when combined with another therapeutic agent. Nearly one-third of the patients enrolled in the nicorandil clinical programme were 65 years old or older. Age-specific side-effects were not identified, and overall, the incidence of the most frequent adverse events in the elderly was similar. There is no evidence that nicorandil induces proarrhythmia, exacerbation of myocardial ischaemia or abrupt withdrawal syndrome. With the progressive titration scheme, no symptomatic decrease in blood pressure was recorded when nicorandil was administered in the range of 10-80 mg.day-1. Heart rate was not significantly affected in the same dose range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370374 TI - Left ventricular hypertrophy: epidemiological prognosis and associated critical factors. AB - Left ventricular hypertrophy (LVH), defined as an abnormal increase in left ventricular mass (LVM), is detected by echocardiography in 16-19% of a general population. Its prevalence is strongly associated with age, systolic blood pressure and obesity. In addition to the assessment of LVM, echocardiography allows different forms of left ventricular remodelling in hypertension to be described: eccentric or concentric, and symmetric or asymmetric LVH. The significance of the different forms, however, is not yet well defined. Increased LVM is now recognized as a powerful, independent risk factor for all cardiovascular diseases. This observation is at variance with the general concept that LVH is a useful adaptation of the left ventricle to chronic overload. To explain this paradox, three hypotheses are proposed: LVH serves as a marker, a limited adaptative process, or a pathological process. Each hypothesis implies different therapeutic approaches; thus it is necessary to clarify the reasons why LVH is such an important risk factor. PMID- 8370375 TI - Therapeutic advances in the treatment of left ventricular hypertrophy. AB - As a consequence of persistently raised blood pressure, left ventricular hypertrophy (LVH) develops as a compensatory mechanism for wall stress induced by the increase in afterload. Recent advances in the fields of molecular biology and genetics are now clarifying the mechanisms involved in the development of LVH. It has been reported that messenger RNA of oncogenes, such as c-fos and c-myc, increases by stretching; these oncogenes contribute to the progression of LVH, the messenger RNA expression of myosin and contractile protein synthesis in the cardiomyocytes. Vasoactive hormones and vascular contracting factors are also reported to have a progressive effect on LVH. In contrast, some antihypertensive agents have been shown to have pharmacological effects on regression of LVH in animals and man. The mechanisms responsible for LVH progression have been extensively studied. In contrast, the mechanisms of LVH regression have not been defined and require elucidation. This paper outlines the basic recognition of the mechanisms of LVH progression and discusses the varied pharmacological actions of calcium antagonists and angiotensin converting enzyme inhibitors on the regression of LVH in man and rats. Although the role of antihypertensive therapy in regression of LVH remains controversial, the calcium antagonist nicardipine appears to have an important role to play in the treatment of LVH in hypertension and in congestive heart failure. PMID- 8370376 TI - Methods for detection of left ventricular hypertrophy: application to hypertensive heart disease. AB - Left ventricular hypertrophy (LVH) detected by electrocardiography (ECG) and, more recently, by echocardiography has been shown to be an extremely strong predictor of morbidity and mortality in patients with essential hypertension and in members of the general population. Increased left ventricular mass (LVM) is strongly related to both increased blood pressure and overweight. Indexation of LVM by body surface or height has advantages for the detection of LVH related to hypertension or obesity. Indexation of LVM for height to the power 2.7 revealed by analysis of growth (allometric) relations may accomplish both these goals. In validation studies, the sensitivity of echocardiography to detect LVH has been reasonably high (85-100%), whereas that of ECG has ranged from as high as 50% in severely diseased necropsy populations to as low as 6-17% in recent studies in Cornell and Framingham. ECG sensitivity can be improved by using Cornell multivariate regression equations or by consideration of the Cornell voltage-QRS duration product. Obesity dramatically decreases the sensitivity of the ECG for detection of LVH, and recent research suggests a lower specificity and a higher rate of false-positive ECG diagnoses of LVH in black than in white subjects. Standard criteria for ECG LVH are less useful than echocardiographic findings for stratifying populations into high- and low-risk subgroups because of lower sensitivity, but improved ECG criteria need further evaluation in this respect. PMID- 8370377 TI - Peroperative nuclear medicine. PMID- 8370378 TI - Dosimetry of iodine-123 iomazenil in humans. AB - The distribution of the central benzodiazepine receptor specific ligand iodine 123 iomazenil was investigated in seven human adults from whole-body scans, blood samples and urine collected up to 24 h after injection. Using 12 source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The urinary bladder wall (0.15 mGy/MBq), lower large intestinal wall (0.071 mGy/MBq) testes (0.044 mGy/MBq) and upper large intestined wall (0.038 mGy/MBq) received the highest absorbed doses. The average effective dose equivalent of 123I-IBZM for adults was estimated to be 0.033 mSv/MBq. PMID- 8370379 TI - Quantitative single-photon emission tomography for tumour blood flow measurement in bronchial carcinoma. AB - A single-photon emission tomography (SPET) technique for the absolute measurement of tumour perfusion is described. Phantom studies have shown that source background ratios are dependent upon source size and radial position within the phantom. A means of correcting source-background count ratios for these variables has been developed and used to correct tumour-lung ratios obtained in 28 patients with bronchial carcinomas who underwent technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO) SPET. On SPET images, the normal lung appears as a relatively homogeneous background. The relationship between 99mTc background concentration (kBq/ml) and counts/pixel was determined from phantom studies and the tumour 99mTc concentration from the background 99mTc concentration and corrected tumour lung ratio. The total activity of the lipophilic 99mTc-HMPAO species injected was measured. The activity reaching the systemic circulation (Asys) was obtained by subtracting the activity trapped in the pulmonary circulation (obtained from background 99mTc concentration and lung volume). Tumour blood flow may then be calculated from fraction of Asys contained in the tumour provided cardiac output and extraction fraction are known. Blood flow through the central region of tumours ranged from zero to 59.0 (mean 14.1) ml min-1 100 g-1 and through the whole tumour from 0.6 to 68.0 (mean 20.6) ml min-1 100 g-1. PMID- 8370380 TI - Influence of the menstrual cycle and of menopause on the gastric emptying rate of solids in female volunteers. AB - The aim of this study was to assess the influence of the normal menstrual cycle and of menopause on the gastric emptying rate of solids. Gastric emptying was studied in 15 premenopausal and ten postmenopausal women with an isotopic technique after the ingestion of a radiolabelled test meal. Premenopausal women were studied twice: within 1 week prior to menses and again 1 week after onset of menses. Postmenopausal women were studied only once. The emptying curves of the solid component of the meal fitted a linear model. The half-emptying time was 78 +/- 5 min during the follicular phase, 75 +/- 7 min during the luteal phase and 76 +/- 6 min in postmenopausal women (differences not statistically significant). The mean percentages of the meal retained in the stomach at different time intervals were also similar in the three groups. These results suggest that the menstrual cycle does not influence the gastric emptying rate of solids, which remains unchanged in relation to the follicular phase or after menopause. PMID- 8370381 TI - Radioisotope assessment of heart damage in hypertransfused thalassaemic patients. AB - Twenty-five thalassaemic patients treated with repeated blood transfusion (BT) and intensive iron removal therapy were studied by echocardiography and rest/stress equilibrium gated radionuclide angiocardiography (EGNA). Stress left ventricular ejection fraction (LVEF) showed an important negative correlation with number of BTs (r = -0.75). Abnormal values of stress LVEF were measured after 200 BTs: these data demonstrate the effectiveness of stress LVEF in the follow-up of patients who have undergone repeated BTs and the clinical importance of intensive chelation therapy. Peak filling rate did not show diagnostic value in the early detection of iron cardiotoxicity. However, its inverse correlation with BT (r = -60) indicates that iron overload depresses the diastolic parameters. PMID- 8370382 TI - Intraoperative, probe-guided curettage of osteoid osteoma. AB - The only curative approach for osteoid osteoma is operative removal of the nidus, but intraoperative detection of the nidus is difficult even when an X-ray amplifier is used. A simple probe-guided operative procedure using technetium-99m methylene diphosphonate is described, and the results and follow-up in 12 patients are reported. In addition physical properties of the probe have been evaluated by phantom measurements. PMID- 8370383 TI - Radiochemical purity of iodine-131 labelled metaiodobenzylguanidine infusion fluids: a report from clinical practice. AB - Iodine-131 labelled metaiodobenzylguanidine ([131I]MIBG) has a diagnostic and therapeutic role in the management of neural crest tumours, particularly neuroblastoma, malignant phaeochromocytoma and paraganglioma. With therapeutic amounts of [131I]MIBG it is essential that the amount of free [131I]iodide, the most important impurity, is known. In clinical practice the percentage of free [131I]iodide seen in a [131I]MIBG infusion concentrate increased from 2.2% +/- 0.67% to 3.6% +/- 0.39% (mean +/- SD; n = 23) 1 day after production. At the time of use the percentage of free [131I]iodide was always below our upper limit of acceptance of 5%. Since 5% of free [131I]iodide is within practical reach in our environment, a higher percentage at the time of preadministration quality control is not accepted in the Netherlands Cancer Institute. PMID- 8370384 TI - Captopril radionuclide test in renovascular hypertension: a European multicentre study. European Multicentre Study Group. AB - The diagnostic work-up of renovascular hypertension is still controversial. The efficacy of renal scintigraphy with technetium-99m diethylene triamine pentaacetate (DTPA) before and after captopril (scintigraphic captopril test) was evaluated in a multicentre study. All 380 hypertensive patients in the study underwent renal arteriography; 125 had renal arterial stenosis > or = 70%, and 54 had a technically successful intervention to correct the stenosis. The post captopril study had a sensitivity of 93% and a specificity of 100% for predicting blood pressure response to intervention, if renal function was normal and a combination of quantitative parameters was applied (individual kidney uptake index < 40%, time to peak activity < 2 min or > 10 min). In the entire population renal artery stenosis > or = 70% was detected with a sensitivity of 83% and a specificity of 93% if renal function was normal. In patients with abnormal renal function the performance of the test was worse, owing to a lower specificity which could be increased by using only time parameters. The performance of the test was optimal when the post-captopril findings were examined; no improvement was achieved by evaluation of the changes induced by captopril from the baseline. The test can thus be simplified by performing only a post-captopril study for routine use: a negative test would exclude a curable form of renovascular hypertension in > 80% and a positive test would predict it in > 90% of the patients selected for suspicion of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370386 TI - Regional cerebral blood flow in Angelman syndrome. AB - A patient with typical features of Angelman syndrome--a genetically inherited disorder involving developmental delay, ataxia, episodes of paroxysmal laughter and brachiocephaly--was studied with single-photon emission tomography. Hypoperfusion found in the left frontal and left temporoparietal regions can provide insights into the functional cerebral pathology, which may be due to a disturbance of the developmental process related to a chromosomal abnormality. PMID- 8370385 TI - The diagnosis of renovascular hypertension: the role of captopril renal scintigraphy and related issues. AB - This article reviews the screening and diagnostic tests used in the detection of significant renal artery stenosis and renovascular hypertension. After addressing the pathophysiological considerations necessary for correct diagnostic test interpretation, this review critically surveys the recent advances in, and the limitations of, relevant investigational procedures and in particular focuses on the efficacy and issues of angiotensin-converting enzyme inhibitor renal scintigraphy. PMID- 8370387 TI - A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis. AB - Synovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, V alpha 11 in SF was expressed to a greater degree in three of five RA patients, and increased levels of V beta 6, 1-3 were found in the SF of four of six RA, compared with paired PB. Of note, V beta 6, 1-3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA-DR types. This was in contrast to two other RA patients, suffering for more than 20 years, who showed different V alpha and V beta usages. beta chain sequence analysis in RA patients with a preference for V beta 6, 1-3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine in the D beta region was noticeable among the predominant SF clones. These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR-directed therapy may, therefore, be useful for the treatment of early RA synovitis. PMID- 8370388 TI - CD23-mediated homotypic cell adhesion: the role of proteolysis. AB - CD23 is a multifunctional molecule expressed by cells of lymphoid, myeloid and hematopoietic lineages. As a cell surface molecule CD23 acts both as a low affinity receptor for IgE (Fc epsilon RII) and as a cell adhesion molecule. CD23 can undergo autoproteolysis to release soluble 37-25-kDa CD23 (s-CD23) molecules with a range of cytokine activities. Here we show a causal link between the two apparently disparate functions of autoproteolysis and cell adhesion. The Epstein Barr virus-transformed B cell line RPMI-8866 formed macroscopic cell clusters solely via CD23. Cell adhesion was inhibited by mAb to CD23 and by IgE. Cell adhesion was also dependent on serum as cells grown in serum-free media failed to form clusters. In serum-free conditions cell adhesion could be induced by the addition of not only 10% FCS but also s-CD23. As s-CD23 is reported to possess proteolytic activity we screened a range of proteases to determine whether they also could induce cell adhesion in serum-free medium. It was found that chymotrypsin and elastase induced cell:cell adhesion in RPMI-8866 cells. The same panel of proteases were screened against a range of CD23-positive (Jijoye, AF-10, T2, U937, ICH-1) and CD23-negative (RPMI-8226, U266, MOLT-4, Ramos) cell lines. It was found that chymotrypsin and elastase induce cell adhesion only in cells expressing CD23. Peptide mapping studies showed that chymotrypsin and elastase cleaved immunoprecipitated CD23 near the same site by which 37-kDa s-CD23 is released (Ala 80). Serum demonstrated no proteolytic activity towards CD23. However, it was found that cells grown in serum-free medium released 25-kDa s CD23 without the need for prior cleavage at the 37-kDa cleavage site. To confirm the role of proteolysis in CD23-mediated cell adhesion we screened a range of protease inhibitors for their ability to antagonize this process. It was found that tosyl-lysine chloromethyl ketone inhibited CD23-mediated cell adhesion. Lactoperoxidase treatment, which inhibits CD23 cleavage, also inhibited cell adhesion. Addition of chymotrypsin and elastase to lactoperoxidase-treated cells induced cell adhesion. From these data we propose that intact CD23 has no demonstrable role in cell adhesion; instead, the portion of CD23 remaining on the cell surface following cleavage appears to mediate cell adhesion. PMID- 8370389 TI - In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild-type p53. AB - The central role of the p53 tumor suppressor gene product in oncogenesis is gradually being clarified. Point mutations in the p53 tumor suppressor gene are common in most human cancers and are often associated with p53 protein overexpression. Overexpressed wild-type or mutant determinants of the p53 protein thus represent an attractive target for immunotherapy of cancer directed against a structure involved in malignant transformation. An important step towards this goal is identification of epitopes of p53 that can be recognized by human cytotoxic T lymphocytes. We identified peptides of (mutant) p53 capable of binding to HLA-A2.1 in an in vitro assay. These HLA-A2.1-binding peptides were utilized for in vitro induction of primary cytotoxic T lymphocyte responses using a human processing-defective cell line (174CEM.T2) as antigen-presenting cell. These cells display "empty" HLA class I surface molecules, that can efficiently be loaded with a single peptide. We obtained CD8+ cytotoxic T lymphocyte clones capable of specifically lysing target cells loaded with wild-type or tumor specific mutant p53 peptides. This strategy allows the in vitro initiation of human cytotoxic T lymphocyte responses against target molecules of choice. PMID- 8370390 TI - Distribution of perforin-containing cells in normal and pregnant mice. AB - Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells elaborate a cytolytic protein named perforin or cytolysin. It was widely held that, in vivo, high quantities of perforin are not present in resting lymphocytes and are usually produced only by activated lymphocytes found under pathological conditions. Until now, only one tissue was known to synthesize abundant quantities of perforin under nonpathological conditions, the uterus during pregnancy. To investigate the possibility that perforin might also be synthesized by other tissues, several tissues besides the uterus from pregnant and normal mice were tested by immunofluorescence and immunoperoxidase for the presence of perforin. The tissues studied were the ears, brain, nasal epithelium, tongue, salivary gland, larynx, thymus, stomach, liver, spleen, small intestine, and lymph nodes; two cell populations with different sizes and levels of perforin expression were found. Large cells, displaying the NK cell phenotype and expressing high levels of perforin, were detected not only in the uterus but also in the salivary gland and lungs of pregnant mice. Small cells, expressing low levels of perforin, were detected mainly in the stomach and small intestine, and they were expressed in both pregnant and normal mice. Taken together, these results imply that perforin containing cells exist in vivo under nonpathological conditions, and that the immune system is endowed with heretofore unknown mechanisms for stimulating the activation of NK cells in a limited number of tissues during pregnancy. PMID- 8370391 TI - Selective activation of resting human gamma delta T lymphocytes by interleukin-2. AB - In rheumatoid arthritis and other inflammatory diseases we and others have found that gamma delta T cells express activation antigens, suggesting that they are involved in the pathogenesis of these disorders. In this study we have stimulated peripheral blood mononuclear cells from normal donors with recombinant interleukin-2 (rIL-2) to see whether such a stimulus alone could activate gamma delta T cells. Short-term exposure (24-96 h) to rIL-2 selectively stimulated the gamma delta but not the alpha beta T cells to express activation antigens (CD69, CD25 and HLA-DR). Long-term culture (2 weeks) in rIL-2-containing medium caused a selective increase in the proportion of the gamma delta T cells and a corresponding reduction of the fraction of alpha beta T cells. Limiting dilution analysis revealed that approximately 1/60 of the gamma delta T cells responded to IL-2 in contrast to only 1/250 of the alpha beta T cells. Comparison of the expression of the IL-2 receptor (IL-2R) alpha and beta chains showed that there was a similar expression of the alpha chain on gamma delta and alpha beta T cells whereas the relative density of the beta chain was more than twice as high on gamma delta T cells. Both the IL-2-induced proliferation of gamma delta T cells and the expression of activation antigens on these cells could be inhibited by an anti-IL-2R beta monoclonal antibody (mAb) but not by an anti-IL-2R alpha mAb. Expression of CD69 on gamma delta T cells was dependent neither on the presence of B cells, monocytes, nor alpha beta T cells. Finally, we found that the IL-2 induced expression of CD69 was inhibited by activation of cAMP-dependent protein kinase and by inhibition of the Src-family of the tyrosine protein kinase, but not by inhibition of protein kinase C or by activation of the CD45 associated tyrosine phosphatase. The ability of gamma delta T cells to be activated by IL-2 is a feature which they have in common with natural killer cells. Moreover, it may be possible that the expression of activation antigens on gamma delta T cells in inflammatory diseases is an epiphenomenon secondary to IL-2 produced by activated alpha beta T cells. PMID- 8370392 TI - DR alpha beta dimers released from complexes with invariant chain fail to stimulate alloreactive T cell clones. AB - To demonstrate that DR alpha beta dimers still complexed to invariant chain (Ii) have not yet acquired peptides recognized by alloreactive T cells, complexes between DR molecules and Ii isolated from Epstein-Barr-virus (EBV)-transformed B cells were analyzed by affinity chromatography and gel filtration. First, it was shown that DR/Ii complexes inserted into artificial planar membranes (PM) failed to stimulate proliferative response of five alloreactive T cell clones and a polyclonal alloreactive T cell line, while PM bearing mature DR alpha beta dimers from the same EBV-B cells were stimulatory for the T cell clones and the T cell line. These findings indicate that either Ii inhibits binding of peptides to DR molecules or Ii hinders T cells recognition of peptide/DR complexes. Second, to discriminate between these two possibilities, DR alpha beta dimers, which were artificially released from complexes between DR molecules and Ii, were inserted into PM. These DR alpha beta dimers were devoid of alloreactive stimulatory capacity while fully capable of binding and presenting a tetanus toxin synthetic peptide to a specific T cell clone, indicating that DR molecules released from complexes with Ii are empty. This study, by showing that DR molecules bound to Ii do not bear peptides recognized by alloreactive T cells, supports the notion that association of Ii with class II major histocompatibility complex (MHC) molecules prevents premature peptide loading and hence favors encounter with peptides derived from proteins of the extracellular compartment. Since allogeneic class II MHC molecules released from complexes with Ii were not stimulatory for five out of five alloreactive T cell clones and a polyclonal alloreactive T cell line, these data also indicate that, in most cases, alloreactive T cells recognize ligands constituted by complexes between allogeneic class II MHC molecules and specific peptides which derive from the antigen-presenting cells themselves or serum proteins. PMID- 8370393 TI - Ontogeny of fetal CD8lo4lo thymocytes: expression of CD44, CD25 and early expression of TcR alpha mRNA. AB - CD8lo4lo cells are the immediate precursors of immature CD8hi4loTcRlo, CD8lo4hiTcRlo and CD8hi4hiTcRlo double-positive (DP) thymocytes in the adult murine thymus. These cells are the first subset in the adult thymus to express accessory CD8 and CD4 molecules, to rearrange the T cell receptor (TcR) alpha chain genes and to express the TcR alpha beta heterodimer at low levels at the surface. Here, we investigate the fetal ontogeny of CD8lo4lo cells. We detect these cells on day 15 of fetal development. They dominate the thymus on day 15.5, to become progressively less prominent thereafter. An important characteristic of fetal CD8lo4lo cells is the early expression of TcR alpha mRNA (on fetal day 15, 36-48 h earlier than reported previously). Our results also suggest, but do not prove, that the receptor may be expressed on the surface as early as day 15.5. Fetal CD8lo4lo cells, like their adult counterparts, become DP in vitro. However, early fetal CD8lo4lo thymocytes express both CD44 and CD25--unlike the adult subset--and that links them to their putative precursors, fetal CD44+CD25+ double negative cells. This finding underscores the difference between adult and fetal thymocytes in turnover of membrane molecules and/or the kinetics of progression through phenotypic stages. PMID- 8370394 TI - Leukemia inhibitory factor production by rat mast cells. AB - Leukemia inhibitory factor (LIF) is a pluripotent cytokine of importance in the regulation of immune and inflammatory responses. This cytokine may play an important role in neuronal development and bone metabolism. We have examined the ability of freshly isolated rat mast cells and mast cell lines to produce LIF at both the mRNA and bioactivity levels. Initial experiments demonstrated that two mucosal mast cell-like cell lines RBL.2H3 and RCMC9 endogenously produced low levels of LIF bioactivity. The production of this cytokine was examined using a hepatocyte-stimulating factor activity assay and confirmed by the use of neutralizing antibodies specific for LIF. This production was enhanced by treatment with the calcium ionophore A23187. No interleukin-6 production was observed by these cells either endogenously or following ionophore activation. Freshly isolated highly purified rat peritoneal mast cells also expressed mRNA for LIF. These results could have important implications for the role of mast cells in neuronal development, hematopoiesis bone metabolism and the acute-phase response. PMID- 8370395 TI - A novel immunosuppressant, IR-1116, which has a different biological mechanism from that of cyclosporine A. AB - The effects of an epifumagillol derivative, IR-1116, on human lymphocytes in vitro, mouse antibody production in vivo and rat renal and cardiac transplantation were investigated. IR-1116 suppressed the human primary mixed lymphocyte reaction (MLR) in a dose-dependent manner with a value of the dose required for 50% suppression of 0.32 microM. IR-1116 suppressed the antibody production by human B lymphocytes activated with pokeweed mitogen or Epstein-Barr virus, but did not affect the interleukin-2 production by human lymphocytes stimulated with phytohemagglutinin. Furthermore, IR-1116 did not have any effect on the proliferation of B or T lymphocytes. IR-1116 is thought to have a different mechanism from cyclosporine A (CsA). BALB/c mice were immunized by s.c. injection of bovine gamma-globulin (BGG) and then received IR-1116 or CsA by i.p. injection at a dose of 20 mg/kg every other day for 2 weeks. IR-1116 suppressed the production of serum antibodies against BGG as strongly as CsA. In this experiment, IR-1116 apparently showed no adverse effects, while CsA-treated mice suffered from diarrhea and appeared to be irritated. Histological studies showed that IR-1116 suppressed the formation of germinal centers in the spleen of immunized mice. Flow cytometric analysis showed that IR-1116 caused a reduction of B lymphocyte population in splenocytes. On the other hand, CsA caused a marked reduction of helper T lymphocyte population in splenocytes and thymocytes. Furthermore, the i.p. administration of IR-1116 prolonged the survival time in a rat renal allograft model and the vital period of grafted hearts in rats. Based on the above, IR-1116 seems to be a new type of immunosuppressant acting via novel mechanisms different from those of immunosuppressants such as CsA, a potent T lymphocyte suppressant. PMID- 8370397 TI - Cholera toxin adjuvant greatly promotes antigen priming of T cells. AB - Cholera toxin (CT) given perorally is a powerful mucosal immunogen and adjuvant. Information that explains the adjuvant effect of CT may be used for the development of more effective oral vaccines and might also contribute to our understanding of the mechanisms involved in regulating mucosal immunity. The present study was undertaken to investigate if CT administered together with keyhole limpet hemocyanin (KLH) would act to promote or inhibit priming of KLH specific T cells and whether the adjuvant effect of CT is restricted to mucosal immune responses or is a generalized phenomenon due to direct immunomodulating effects of CT. We found that CT adjuvant greatly augmented the effectiveness of a single oral priming immunization with KLH: re-challenge with KLH in vitro 1 week following immunization gave several-fold stronger proliferation in KLH-specific spleen, mesenteric lymph node, Peyer's patch and gut lamina propria T cells from KLH + CT adjuvant as opposed to KLH only-treated mice. Moreover, several-fold stronger cytokine production, i.e. interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10 and interferon-gamma accompanied the enhanced proliferative response of T cells from CT adjuvant-treated mice. The adjuvant effect of CT was not restricted to mucosal immune responses but was evident also following a single parenteral immunization with KLH + CT. Limiting dilution analysis revealed that CT adjuvant promoted a 20- to 40-fold increase in the frequency of primed KLH-specific T cells. Phenotypic and functional analyses clearly demonstrated that CT adjuvant primarily enhanced priming of CD4+ rather than CD8+ T cells and the pattern of lymphokine secretion disclosed that CT most probably promoted antigen priming of both Th1 and Th2 type of CD4+ T precursor cells. PMID- 8370396 TI - Activator protein-1 (AP-1) is stimulated by microbial superantigens in human monocytic cells. AB - Microbial superantigens bind to major histocompatibility complex (MHC) class II molecules and activate gene transcription in monocytes. In search of transcription factors that potentially mediate the effects of superantigens at the nuclear level, we examined the capacity of staphylococcal superantigens to stimulate the activity of the transcriptional promoter factor activator protein-1 (AP-1). Electrophoretic mobility shift assays showed an increase in nuclear proteins that bound to the consensus AP-1 motif within 5 min following the stimulation of the monocytic cell line THP-1 with toxic shock syndrome toxin-1 (TSST-1) or staphylococcal endotoxin A. We show that mRNA levels for the subunits that compose AP-1, the protooncogenes c-fos and c-jun, are upregulated by stimulation of THP-1 cells with TSST-1. The activated AP-1 complexes were functional, as evidenced by the capacity of TSST-1 to stimulate the expression of an AP-1-driven reporter gene construct transfected into THP-1 cells. These results establish that the engagement of MHC class II molecules by superantigens increases the activity of functional AP-1 complexes and that this may proceed in part by transcriptional activation of c-fos and c-jun protooncogenes. PMID- 8370398 TI - Somatic hypermutation in 5' flanking regions of heavy chain antibody variable regions. AB - The aim of this study has been to determine the distribution of somatic mutations in the 5' flanking regions of rearranged immunoglobulin heavy chain variable region genes (VDJ). We sequenced the 5' flanking region in 12 secondary immune response antibodies produced in C57BL/6j mice against the hapten (4-hydroxy-3 nitrophenyl)acetyl (NP) coupled to chicken-gamma-globulin. In these and previously published sequences, almost 97% of the mutations occurred in the transcribed region of the gene, and only a minority of genes (5/29) contained mutations upstream of the transcription start (cap) site. No potential germ-line donor was found for a cluster of five base changes previously found in a single heavy chain gene, 3B62. However, the uniqueness of this mutational cluster and its distance from the normally mutated region suggests that the nucleotide changes may not be due to the normal mutator mechanism. Thus, as this was the only instance of somatic mutations that far upstream of the promoter/cap site region, the reverse transcriptase model for somatic hypermutation is still a possibility. The data are consistent with a mutational mechanism that requires transcription of the rearranged target V(D)J gene which appears to result in the generation of a positively skewed asymmetrical distribution of somatic mutations. A single mode is centered near the V(D)J and a long tail extends into the 3' non translated region of the J-C intron. Two classes of model could explain this mutation distribution pattern: those where transcription products (RNA, cDNA) are the direct mutational substrates, or those that postulate local unfolding of the chromatin around a V(D)J rearrangement directly exposing the DNA of the transcribed region to specific mutational enzymes. PMID- 8370399 TI - The evolutionary origin of the major histocompatibility complex: polymorphism of class II alpha chain genes in the cartilaginous fish. AB - T cells recognize antigen (Ag) in the form of peptides bound to the major histocompatibility complex (MHC) molecule. One of the important issues in evolutionary immunology is to identify the stage in phylogeny when this mode of Ag recognition emerged. At present, there is a considerable controversy as to whether the cartilaginous fish have the bona fide MHC. In our previous study, we showed that the nurse shark, a member of the cartilaginous fish, has (a) gene(s) capable of encoding MHC class II alpha chains. In the present study, we examined the polymorphism of nurse shark MHC class II alpha chain genes designated Gici DAA and Gici-DBA using the polymerase chain reaction. The Gici-DAA and Gici-DBA genes had six and five alleles, respectively, and individual alleles usually differed by multiple nucleotides. In addition, most of the nucleotide substitutions were located at the putative Ag-binding sites, where non-synonymous substitutions occurred more frequently than synonymous substitutions. The fact that the Gici-DAA and Gici-DBA genes display a polymorphism pattern essentially similar to that of mammalian MHC genes playing a major role in Ag presentation suggests that the cartilaginous fish have the bona fide MHC. Thus, the MHC peptide-based T cell recognition system appears to have arisen at or before the emergence of the cartilaginous fish. PMID- 8370400 TI - C1q, the collagen-like subcomponent of the first component of complement C1, is a membrane protein of guinea pig macrophages. AB - C1q, a subcomponent of C1--the first component of complement, is synthesized by macrophages (M phi). Immunofluorescence and immunoperoxidase studies first indicated the presence of C1q on the surface of guinea pig (gp) and human peritoneal M phi (Loos, M., Storz, R., Muller, W. and Lemmel, E. M., Immunobiology 1981. 158: 213). In our study different methods for labeling of gp serum and gp M phi C1q were employed. The presence of C1q protein on the surface of gp peritoneal M phi is shown by cell surface labeling with the biotin derivative sulfosuccinimdyl-6-(biotinamido)-hexanoate and subsequent immunoprecipitation. The mechanism by which C1q is attached to the cell membrane was also investigated. Intact cells were treated with acid stripping-buffers or phosphatidylinositol-specific phospholipase C and separated membranes were extracted with a buffer containing 1 M KCl and 3 M urea. Regardless of which method was used, C1q remained attached to the membrane. When surface-labeled cells were cultured, they were found to release the C1q from their surface membrane into the culture medium. Lysates of biosynthetically labeled cells were used to show that, like secreted or serum C1q, cellular M phi C1q binds to immobilized homologous IgG. This implies that the globular regions of the cellular C1q are functionally active. The results reveal that (i) cellular M phi C1q is firmly located in the membrane throughout the biosynthetic pathway, such that it is comparable with an integral membrane protein, (ii) cellular M phi C1q is not reversibly bound to the cell surface via a receptor. We suggest that C1q, as a membrane protein of M phi, serves as an Fc binding factor that also is secreted into the environment. PMID- 8370401 TI - Modification of the anti-CD3-induced cytokine release syndrome by anti-interferon gamma or anti-interleukin-6 antibody treatment: protective effects and biphasic changes in blood cytokine levels. AB - Anti-interferon-gamma (IFN-gamma) antibodies were found to protect mice against pathological changes induced by injection of anti-CD3 antibody: incidence of diarrhea, severity of hypothermia and mortality rates were dramatically reduced. In anti-IFN-gamma antibody-treated mice, IFN-gamma blood levels were significantly reduced at 1.5 h post anti-CD3 challenge, but more elevated levels were found from 4 to 24 h. This rebound-like IFN-gamma response coincided with more profound hypoglycemia. Tumor necrosis factor and interleukin (IL)-6 levels were not affected by anti-IFN-gamma treatment. Exogenous IFN-gamma, administered within 3 h (but not later) of the anti-CD3 challenge made the syndrome worse. Furthermore, inter-mouse strain differences in sensitivity to the anti-CD3 syndrome correlated with the ability of the strain to produce IFN-gamma. Anti-IL 6 antibodies provided only marginal protection against hypothermia and mortality, but did markedly reduce hypoglycemia. Levels of biologically active IL-6 in serum were not influenced by anti-IL-6 antibody treatment during the first few hours after anti-CD3 challenge, but were significantly increased at later times. The data provide evidence that endogenous IFN-gamma is a critical element in the early phase of the anti-CD3 syndrome; endogenous IL-6, while possibly being involved in hypoglycemia, seems of lesser importance for the outcome of the syndrome. PMID- 8370402 TI - Interleukin-4 and interleukin-10 synergize to inhibit cell-mediated immunity in vivo. AB - The lack of cell-mediated (TH1-like) immunity that is often associated with strong humoral immune responses is thought to be due in part to the inhibition of Th1 effector function by the Th2-derived cytokine interleukin-10 (IL-10). This hypothesis, however, is based entirely on results from in vitro studies, wherein IL-10 has been shown to inhibit Th1 cytokine synthesis. In this study we have compared the regulatory effects of both IL-4 and IL-10 on the development of a more complex Th1 effector function in vivo, the development of delayed-type hypersensitivity (DTH) to Leishmania major in mice immune to Leishmania. The results revealed two findings unexpected from in vitro studies with Th1 clones. First, optimal inhibition of the DTH response (up to 70%), assessed by footpad swelling and leukocytic infiltration, required the combination of IL-4 and IL-10, indicating that these two activities synergized to inhibit DTH reactivity. Second, IL-4 inhibited interferon-gamma (IFN-gamma) production by lymph node cells draining the site of antigen challenge as well as did IL-10. The combination of both cytokines was no more effective than either alone. The mechanism by which IL-4 and IL-10 acted to inhibit DTH responses did not appear to be through inhibition of IFN-gamma or tumor necrosis factor production as treatment with antibodies which neutralized these activities failed to inhibit DTH responses. Inhibition of the DTH with IL-4 and IL-10 is the most effective specific regulator of DTH responses reported and the only one capable of modulating tuberculin DTH. These data establish IL-4 and IL-10 as potent inhibitors of Th1 effector function in vivo and suggest their utility in controlling deleterious Th1-mediated inflammatory responses such as occur in some infectious and autoimmune diseases. PMID- 8370403 TI - Growth requirements for avian gamma delta T cells include exogenous cytokines, receptor ligation and in vivo priming. AB - These studies analyze growth requirements for the normal gamma delta T cell population in peripheral lymphoid tissues. Avian gamma delta T cells can respond well to T cell mitogens in the presence of alpha beta T cells, but our studies indicate that they do not grow well alone. Exogenous growth factors were required in order for gamma delta T cells to proliferate in response to receptor ligation by anti-T cell receptor antibodies or other T cell mitogens. Interleukin-2 was implicated as one of the necessary growth factors that the gamma delta cells cannot produce adequately on their own. The response to dual stimulation (receptor ligation plus exogenous T cell factors) was attributable to a discrete subpopulation of gamma delta T cells that could be identified by their cell surface CD8, major histocompatibility complex class II expression and relative increase in cell size. Conversely, non-responsive gamma delta T cells did not exhibit these activation markers. These observations suggest a physiological basis for the relatively late appearance of gamma delta T cells in inflammatory responses and their failure as a population to match the growth potential of alpha beta T cells. More importantly, the results imply that the biological role of gamma delta T cells must be understood within the context of their interaction with alpha beta T cells. PMID- 8370404 TI - Natural killer cells participate in the early defense against Leishmania major infection in mice. AB - In this study the role of natural killer (NK) cells in the course of experimental Leishmania major infection was investigated. NK cells in genetically resistant C57BL/6 mice were depleted by in vivo administration of anti-asialo-GM1 or anti NK1.1 antibodies. A marked exacerbation of the infection was found in the NK depleted mice within the first two weeks of infection. Both the local tissue swelling and the number of parasites in the lesions were significantly higher than in normal animals. Lymph node cells taken from infected NK-depleted mice released less interferon-gamma (IFN-gamma) when cultured in vitro. As an alternate approach we have used poly I:C treatment in order to activate NK cell activity in vivo in BALB/c mice, which are genetically susceptible to L. major infection. Poly I:C treatment led to milder symptoms and to a significantly lower parasite burden in the early course of infection. Lymph node cells from infected and poly I:C-treated BALB/c mice released higher amount of IFN-gamma in vitro than cells from control mice. These data show that NK cells are active participants in the non-specific phase of anti-leishmanial activity in the control of parasite multiplication early in the course of L. major infection in mice. PMID- 8370405 TI - Plasmodium berghei-specific T cells respond to non-processed sporozoites presented by B cells. AB - The mechanism of malaria protective immunity induced by immunization with radiation-attenuated Plasmodium sporozoites (SPZ) is only partially understood. For example, B and T cell responses specific for the circumsporozoite (CS) protein, a 46 kDa SPZ surface protein, have been characterized; however, events leading to SPZ-specific T cell activation, i.e., processing and presentation of SPZ by antigen-presenting cells have not been investigated. In the present study we describe the in vitro analysis of requirements for accessory cell function in the presentation of SPZ to SPZ-immune T cells. The results establish that SPZ induced proliferative T cells are reactive to non-processed SPZ presented by activated B cells and, thus, imply that the non-processed form of the SPZ associated CS protein restricts the induction of the potential CS protein T cell repertoire. PMID- 8370406 TI - Class I-deficient resistant mice intracerebrally inoculated with Theiler's virus show an increased T cell response to viral antigens and susceptibility to demyelination. AB - Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination in susceptible mouse strains. The histology of TMEV-induced demyelination is similar to that seen in patients suffering from multiple sclerosis. It was previously shown that the susceptibility of mice to TMEV-induced demyelination in certain strain combinations is closely associated with the major histocompatibility complex (MHC) class I locus. Here we examine disease susceptibility of beta 2 microglobulin (beta 2M)-deficient transgenic mice lacking class I expression and functional CD8+ T cells. In contrast to TMEV-infected parental C57BL/6 mice, the transgenics develop high levels of virus-specific DTH and T cell proliferation accompanied by an increased frequency of central nervous system (CNS) demyelinating lesions. However, clinical signs of demyelination were not noted. Neither antibody titer nor viral persistence were significantly affected in the beta 2M-deficient mice. These results suggest that in the absence of functional class I/CD8+ cells, the class II-restricted T cell response to TMEV is enhanced and CNS pathogenesis is heightened, although the level is not severe enough to result in clinical disease. When the TMEV-infected mice were subcutaneously immunized with virus, however, the beta 2M-deficient mice displayed clinical symptoms. Therefore, our results strongly suggest that CD8+ T cells do not directly contribute to CNS demyelination. In contrast, such T cells appear to be primarily involved in down-regulation of a potentially damaging CD4+ T cell response in resistant animals, although some of the T cells may play a role in clearing viral persistence in the CNS, resulting in the protection of the host from viral demyelination. PMID- 8370407 TI - Role of transforming growth factor-beta in the preferential induction of T helper cells of type 1 by staphylococcal enterotoxin B. AB - Stimulation of murine CD4+ T cells with staphylococcal enterotoxin B (SEB) results in the preferential development of T helper (Th) 1 cells [i.e. high interferon (IFN)-gamma and low interleukin (IL)-4, IL-5 and IL-10]; whereas in response to plate-bound anti-CD3 or anti-T cell receptor-alpha beta, Th1 as well as Th2 cells develop. In the present study, we examined the mechanism which is responsible for the selective Th1 development in the SEB system. The addition of IL-4 resulted in a strong development of Th2 cells showing that SEB stimulation can result in Th2 differentiation. Co-stimulation with anti-CD28 was insufficient in this regard. Lack of Th2 development in the SEB system was in part due to the inhibitory effect of endogenously produced transforming growth factor-beta (TGF beta), because anti-TGF-beta allowed the development of Th2 cells. Similarly, TGF beta inhibited Th2 development and stimulated Th1 development in the anti-CD3 system. This shift was only partially prevented by also including IL-4 in the cultures. The effects of TGF-beta could only partially be explained by stimulation of IFN-gamma or inhibition of IL-4 as intermediatory cytokines: (1) TGF-beta stimulated Th1 development even in the presence of anti-IL-4 and anti IFN-gamma, and (2) a strong inhibitory effect of anti-TGF-beta on Th1 development was still observed when anti-IL-4 and IFN-gamma were simultaneously added to the cultures. It is concluded that SEB favors Th1 development by stimulation of TGF beta production. Inhibition of Th2 development by TGF-beta is due, in part, to inhibition of IL-4 and stimulation of IFN-gamma, and, in part, to a direct effect of TGF-beta on the responding T cells. PMID- 8370408 TI - A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily. AB - The antibodies Ki-M8, Ber-Mac3, GHI/61 and SM4 define a human macrophage associated antigen with a relative molecular mass of 130,000 which we designate M130. The protein was purified by immunoaffinity chromatography and an N-terminal and three internal amino acid sequences were obtained. A cDNA fragment was initially obtained by polymerase chain reaction (PCR) using reverse-translated primers. Several variant cDNA clones, derived from alternative spliced messages, were obtained from a lipopolysaccharide-stimulated human monocyte library and were sequenced. The relative abundance of these variants was evaluated by a series of overlapping PCR reactions. The size of the most representative cDNA is 3.7 kb and closely agrees with the mRNA size of 3.8 kb determined by Northern blot analysis. The membrane protein encoded contains a leader peptide of 40 residues, a putative extracellular domain of 1003 residues, followed by a hydrophobic segment of 24 residues and a cytoplasmic domain of 49 residues. The extracellular domain was found to contain nine repeating elements, of about 110 residues, which are similar to those of the scavenger receptor superfamily. PMID- 8370409 TI - B cells are anergic in transgenic mice that express IgM anti-DNA antibodies. AB - B lymphocytes in individuals with systemic lupus erythematosus (SLE) secrete pathogenic autoantibodies to DNA which cause clinical nephritis. (NZB X NZW) F1 (BW) female mice also secrete pathogenic anti-DNA autoantibodies, and therefore are considered to be an animal model of SLE. The rearranged immunoglobulin (Ig) genes that encode an anti-DNA antibody from a diseased BW mouse have been cloned, and transgenic (Tg) mice have been created by microinjection of these constructs into fertilized eggs from normal mice. As we reported previously, when the construct contains the C gamma 2a heavy chain constant (CH) region, the mice spontaneously secrete anti-DNA IgG and they develop mild nephritis. This demonstrated that the Ig encoded by the transgene is pathogenic. In contrast, here we report that when the construct contains the same anti-DNA Ig variable (V) regions used previously, along with the C mu region, the autoreactive B cells are rendered tolerant. Most B cells in the Tg mice express the mu transgene product on their surface, and rearrangement of endogenous light chain genes is partially suppressed. Furthermore, most hybridomas made from Tg B cells secrete IgM anti DNA. Despite this, the Tg mice have reduced levels of total serum Ig and they do not secrete anti-DNA IgM either spontaneously or following immunization with DNA. We conclude that most B cells in the Tg mice have been rendered anergic. Anergy is however reversible in vitro; lipopolysaccharide stimulation of Tg B cells leads to the production of a significant amount of IgM anti-DNA antibody. The studies demonstrate that in this line of Tg mice on a normal mouse genetic background potentially pathogenic B cells that express a high-affinity Ig specific for a natural autoantigen are subject to tolerance by induction of anergy. PMID- 8370410 TI - Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions. AB - Endoglin is an homodimeric membrane antigen with capacity to bind transforming growth factor-beta (TGF-beta) and whose expression is up-regulated on myeloid cells upon differentiation to macrophages. We have isolated full-length cDNA clones from a lambda gt 10 library, prepared from phorbol 12-myristate 13-acetate differentiated HL60 cells by screening with an endoglin-specific cDNA probe from endothelial cells. Sequencing of the largest clone (3073 bp), revealed that the leader sequence contains 25 residues and that the 586 amino acids of the extracellular and transmembrane domains were identical to those described for endothelial endoglin. However, the cytoplasmic tail encoded by this cDNA clone contains only 14 amino acids as opposed to the 47 residues previously reported, suggesting the existence of two alternative endoglin variants. The expression of these isoforms was demonstrated by polymerase chain reaction analyses on endothelial cells, myelomonocytic cell lines HL-60 and U-937, and placenta. Independent cDNA constructs corresponding to both forms were transfected into mouse fibroblasts leading to the expression of two distinct endoglin molecules. Both forms were shown to bind TGF-beta 1 and, when overexpressed in transfected mouse fibroblasts, to form disulfide-linked homodimers, indicating that the cysteine residues present in the extracellular domain are responsible for the dimerization. PMID- 8370411 TI - Construction, expression and functional analysis of a glycolipid-linked form of CR1. AB - By genetic engineering of human CR1 cDNA and its stable transfection into cells we have produced a cell line which expresses CR1 anchored to the cell surface by a glycolipid anchor. The glycosyl-phosphatidylinositol (GPI)-CR1 protects cells intrinsically from damage mediated by complement activated through the classical pathway. Cell surface GPI-CR1 is more efficient on a molar basis than soluble CR1 in the assay, but extrinsic protection of other cells was not obtained. Soluble CR1-protected cells extrinsically in the assay but was required at nearly ten fold higher amounts than the intrinsic protection conferred by GPI-anchored CR1. Additionally, GPI-CR1 was shown to act as a co-factor to Factor I in the generation of C3c from iC3b. Since GPI-anchored proteins can incorporate spontaneously into the membranes of living cells by virtue of their lipid tails, the isolated GPI-CR1 will be used to introduce CR1 on to the surfaces of many different types of cell so that its role in immunity can be further investigated. PMID- 8370412 TI - Autoimmune syndrome after induction of neonatal tolerance to I-E antigens. AB - Neonatal injection of semiallogeneic spleen cells induces a state of specific tolerance to the parental alloantigens, but also the development of an autoimmune syndrome known as host-versus-graft disease (HVGD). The autoimmune features are a consequence of the allogeneic cooperation between persisting alloreactive host T helper type 2 (TH2) cells and donor semiallogeneic B cells. It has been established that I-A alloantigens play a central role in the triggering of this HVGD. Here it was investigated if I-E antigens, which have shown functional differences, regarding autoimmunity and alloreactivity, with respect to I-A antigens, are also able to trigger this autoimmune syndrome. The injection of spleen cells from [B10.A(4R) x B10.A(2R)]F1 (I-E+) hybrid mice into newborn B10.A(4R) (I-E-) mice was accompanied by the establishment of chimerism and also by the development of a characteristic, but moderated, HVGD. The weak intensity of this HVGD is likely due to the moderation of the alloreactive responses induced against I-E molecules. Moreover, the marked increase in the levels of IgE and in the titers of anti-DNA IgG1 antibodies strongly suggest that alloreactive TH2 cells play also a main role in the autoimmune syndrome following tolerization to I-E antigens. Therefore, it is concluded that the I-E and I-A isotypes are functionally similar with respect to the allogeneic cellular interactions that account for the HVGD. PMID- 8370413 TI - Cloning of a human immunoglobulin gene fragment containing both VH-D and D-JH rearrangements: implication for VH-D as an intermediate to VH-D-JH formation. AB - In an Epstein-Barr virus-transformed human B cell line we found an unusual immunoglobulin heavy chain gene rearrangement. Restriction mapping and sequencing analysis led us to conclude that VH-D and D-JH recombination took place in a single allele. Both VH-D and D-JH complexes still had their recombination signal sequences adjacent and the DNA sandwiched by these two complexes retained a germ line configuration, suggesting the potential for a secondary rearrangement resulting in a VH-D(-D)-JH formation. With this finding, we propose a novel pathway, in which the VH-D complex is an intermediate in the formation of a functional VH exon. PMID- 8370414 TI - Linomide, a novel immunomodulator that prevents death in four models of septic shock. AB - Intravenous injections of 50 micrograms Staphylococcus aureus enterotoxin B (SEB) or bacterial lipopolysaccharide (LPS) are lethal, provided that mice are simultaneously sensitized with either N-galactosamine (GalN) or the anti glucocorticoid RU-38486. Similar to the synthetic glucocorticoid (GC) receptor agonist dexamethasone, pharmacological doses of the immunomodulator linomide (quinoline-3-carboxamide) prevent death in all four models of lethal septic shock (LPS + GalN, LPS + RU-38486, SEB + GalN, and SEB + RU-38486) and inhibit the secretion of tumor necrosis factor, one of the major intermediate effector molecules of SEB and LPS toxicity. In this system, cyclosporine A (CsA), although effective in suppressing SEB toxicity, fails to counteract the lethal effect of LPS. This observation, together with the fact that linomide acts in the presence of excess amounts of GC receptor antagonist, indicates that linomide functions in a different way to that of known immunosuppressive agents like CsA and GC. PMID- 8370415 TI - Increased cytokine production in mononuclear cells of healthy elderly people. AB - The production of cytokines during aging, except interleukin (IL)-2, has been neglected in humans. We measured the in vitro production of IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and IL-1 beta by peripheral mononuclear cells from selected healthy young (mean age 26.8 years) and aged (mean age 80.2 years) subjects. Significant increases of IL-6, TNF-alpha and IL-1 beta levels were found in mitogen-stimulated cultures from aged donors, occurring at 24 to 72 h after stimulation. No significant differences were observed for IFN gamma production. Proliferative capability of cells stimulated with PHA was not impaired in aged subjects. Since the amounts of all cytokines studied were similar in unstimulated cultures from young and aged subjects, and also serum levels of TNF-alpha did not differ, these data indicate that the cellular machinery for the production of these cytokines is well preserved in aging, and also that cells from old people are able to up-regulate their production in response to appropriate stimuli. The increases in cytokine synthesis were not dependent on changes in the number of monocytes, nor were they related to the significant rise of CD45RO+, and the concomitant decrease of CD45RA+, occurring in both CD4+ and CD8+ lymphocytes from aged subjects. The increased production of pro-inflammatory cytokines by stimulated mononuclear cells of healthy aged subjects may be relevant to several aspects of age-associated pathological events, including atherosclerosis, osteoporosis, fibrosis and dementia. PMID- 8370416 TI - Autoimmune gld mutation uncouples suicide and cytokine/proliferation pathways in activated, mature T cells. AB - Antigen receptor-directed suicide plays an important role in the elimination of potentially autoaggressive immature T cells during thymic differentiation. Here we demonstrated evidence for a second pathway of receptor-directed suicide in mature T cells that is missing in a mutant strain (gld) of mice with an "autoimmune" lymphoproliferative syndrome. The defect is evident within the gld activated T cell and does not require the presence of an antigen-presenting cell for its expression. Receptor-driven suicide is intact in immature T cells of animals with this mutation. These results support the significance of receptor directed suicide in the mature T cell compartment and suggest that the immune system may use three independent pathways for regulating programmed cell death in shaping and controlling the immune response. PMID- 8370417 TI - Hyper-reactivity of mouse CD45RA- T cells. AB - Mouse CD4 T cells have been partitioned into CD45RA and CD45RA- subpopulations by means of the monoclonal antibody 14.8. The CD45RA- subpopulation proliferated more actively and generated more interleukin-4 (IL-4) in response to stimulation with anti-CD3 antibody and phytohemagglutinin, and more IL-2 in response to anti CD3. This subpopulation is therefore hyper-reactive to these polyclonal stimulators, but does not show the bias towards T helper type 2 activity that has been found in studies with other related CD45 isoforms. No evidence of suppression was obtained by comparing proliferation of CD45RA- cells in the presence and absence of CD45RA cells. Thus mouse CD4 T cells behave in these respects similarly to those of man, as is evident in a brief review of the quiescence-activation-quiescence cycle in the two species. PMID- 8370418 TI - Increased colony growth in peripheral blood cultures from patients with ALL depends on immunological subtype. AB - The proliferative capacity of precursor cells in bone marrow and peripheral blood of 19 patients with acute lymphoblastic leukaemia (ALL) at diagnosis was studied and results were compared with the immunophenotype of the leukaemic population. Bone marrow proliferative capacity in these patients was strongly diminished, low or absent, independent of the immunophenotype, compared with control values (p < 0.0002). In contrast, the growth pattern in peripheral blood cultures from the same patients varied widely according to the subtype of ALL: whereas in patients with undifferentiated ALL [TdT+, HLA-DR+, CD19+ or-, CD10-, (n = 4) or CD7+, CD5+, CD1-, CD4- and CD8- (n = 1)] PB had strongly reduced proliferative capacity compared with control (p < 0.05), there was excess growth of normal neutrophil and erythroid colonies in BP cultures from patients with a more mature immunophenotype of either B-[CD10+, (n = 11)] or T [CD1+, CD4+ and/or CD8+, (n = 3)] phenotype. This phenomenon was only seen in patients who had circulating lymphoblasts: If their number was low, growth was so prolific that single colonies could not be identified. In the presence of a high blast count, colony growth was less prolific--probably due to a "dilution" effect--but still higher than normal (p < 0.05). We conclude that, in relatively mature ALL of the B- and the T-cell line, the presence of circulating lymphoblasts is associated with increased PB proliferative capacity. PMID- 8370419 TI - Brain perfusion in polycythaemia using 99TcmHMPAO: effect of treatment. PMID- 8370420 TI - Complete cytogenetic and molecular remission in a case of lymphoid blast crisis in chronic myeloid leukemia with intensive chemotherapy and interferon alpha. PMID- 8370421 TI - IFN-gamma and TNF-alpha secretion by CD4+ and CD8+ TCR alpha beta + T-cell clones derived early after allogeneic bone marrow transplantation. AB - Secretion of the potentially antileukaemic cytokines IFN-gamma and TNF-alpha was investigated for CD4+ and CD8+ TCR alpha beta + T-cell clones derived from 4 leukaemia patients 3-6 weeks after allogeneic BMT. We investigated cytokine secretion in response to the activation signal accessory cells+phytohaemagglutinin+Interleukin 2. All clones derived after BMT were capable of IFN-gamma and TNF-alpha secretion, and both for CD4+ (n = 96) and CD8+ (n = 8) T cells quantities of IFN-gamma and TNF-alpha were significantly correlated with one another. When comparing the overall results for posttransplant and normal T-cell clones derived from 2 bone marrow donors (n = 65), both CD4+ and CD8+ TCR alpha beta + T-cell clones showed increased IFN-gamma production, and CD4+ but not CD8+ clones showed a decreased TNF-alpha secretion. The results suggest that noncytotoxic T cells derived after allogeneic BMT can produce IFN-gamma and TNF-alpha and may thus be capable of mediating antileukaemic effects. PMID- 8370422 TI - Multiple myeloma treated with mitoxantrone in combination with vincristine and prednisolone (NOP regimen) versus melphalan and prednisolone: a phase III study. Nordic Myeloma Study Group (NMSG). AB - One-hundred-and-fifty-one patients with previously untreated multiple myeloma were allocated to treatment with either NOP regimen (mitoxantrone 16 mg/m2 and vincristine 2 mg day 1 and prednisolone 250 mg day 1-4 and 17-20) or M+P regimen (melphalan 0.25 mg/kg and prednisolone 100-200 mg/day day 1-4). Both regimens were repeated every 4 weeks and were scheduled for 1 year. Seventy-seven patients were treated with NOP and 74 patients with M+P. No major clinical differences were recorded between the groups before treatment. Sixty percent of the patients responded (CR+PR) to NOP versus 64% to M+P (NS). The time to progression was 16 months (95% C.L. 14-51) in the NOP group versus 21 months (95% C.L. 15-27) in the M+P group (NS). The median survival was 14 months (7-21) in the NOP group and 31 months (21-43) in the M+P group (p = 0.02). NOP was significantly more toxic than M+P. Seven patients treated with NOP died due to infection and neutropenia and 1 patient died of cardiac toxicity, in contrast to 1 death due to infection and neutropenia in the M+P group. Gastrointestinal toxicity was acceptable in both groups. In conclusion, NOP was inferior to M+P as primary treatment of multiple myeloma. PMID- 8370423 TI - Cadmium-induced changes of antioxidant and metabolic status in red blood cells of rats: in vivo effects. AB - Chronic exposure of adult rats to dietary intake of cadmium (15 mg CdCl2/day/kg for 30 days) leads to development of anemia and thrombocytosis. Anemia is characterized by significant reticulocytosis (13.1 +/- 1.0%), anysocytosis, poikilocytosis, iron deficiency and marked alterations of antioxidant and metabolic status of red blood cells. Activities of SOD, catalase, GPx and GR were significantly increased in red blood cells of cadmium-treated rats. In treated animals cadmium induced an increase of red cell reduced and oxidized glutathione with no changes of GSSG/GSH ratio. However, significant reduction of lipid peroxidation was found. Plasma levels of tocopherol and ascorbate, as well as activity of glutathione-S-transferase, were all significantly increased in cadmium-treated rats. The energy metabolism of red blood cells was deeply altered in cadmium-treated rats. The levels of ATP, ADP, AMP and TAN were significantly increased while ATP/ADP ratio and adenylate energy charge (AEC) were significantly reduced. The level of 2,3-BPG was somewhat lower, but 2,3-BPG/Hb ratio was considerably higher, in red blood cells of cadmium-treated rats. PMID- 8370424 TI - Fludarabine in patients with advanced and/or resistant B-chronic lymphocytic leukemia. AB - In this study, we evaluated the efficacy of fludarabine (FLU), an adenine nucleoside analogue, in 35 previously treated patients with advanced and progressed B-cell chronic lymphocytic leukemia (B-CLL) and in 6 at diagnosis. All patients were treated at a dose of 25 mg/m2 per day for 5 consecutive days (mean number of courses was 5, with a range from 4 to 6). The majority of patients experienced a beneficial effect on hematological parameters. In particular, a remarkable reduction of lymphocyte count together with an increase of neutrophils and platelets was observed. The overall response rate was 42% with 1 complete response and 16 partial responses. Ten patients achieved minor responses and the remaining 14 showed no benefit from treatment. An increased response rate was achieved in 6 untreated patients who showed an overall response rate of 67% (4/6). The major complications observed were neutropenia (66%) and febrile episodes (44%) that were generally infection-related and were fatal in 3 cases. Because we were dealing with patients whose disease was advanced and/or resistant to treatment, the overall results may be considered encouraging with acceptable toxic reactions not superior to those frequently observed with polychemotherapy. PMID- 8370425 TI - Corticosteroid is not beneficial in multiple-drug combination chemotherapy for multiple myeloma. Finnish Leukaemia Group. AB - In a randomised multicentre trial a combination of methylprednisolone, vincristine, lomustine, cyclophosphamide and melphalan (MOCCA) was compared with the same regimen omitting methylprednisolone after the first course (COLA) in previously untreated patients with multiple myeloma. The MOCCA arm showed a response rate of 72% among 79 patients and the COLA arm a response rate of 60% among 59 patients. This difference was not statistically significant. The median survival time was 56 months in the MOCCA arm and 61 months in the COLA arm. There was a slight increase of early deaths (within the first 6 months) in the MOCCA arm as compared with the COLA arm. We conclude that, in multidrug therapies, the continuation of corticosteroid at conventional dosage beyond the first course does not improve response rate or survival time in multiple myeloma. PMID- 8370426 TI - Factors contributing to dyspnoea during bronchoconstriction and exercise in asthmatic subjects. AB - The purpose of the present study was to identify: 1) whether dyspnoea during bronchoconstriction and exercise is related, in asthmatic subjects; and 2) to what extent baseline pulmonary function and respiratory muscle strength contribute to dyspnoea under both conditions. One hundred and seventy five consecutive subjects, referred with suspected asthma, rated the intensity of dyspnoea (Borg scale 0-10): 1) during the administration of doubling concentrations of methacholine to 32 mg.ml-1 methacholine, or until the baseline forced expiratory volume in one second (FEV1) was reduced by 20%; and 2) during incremental cycle ergometry (100 kpm.min-1 each minute) to maximal capacity. 138/175 subjects achieved a 20% reduction in their baseline FEV1; 18 of the 138 were excluded, 2 children and 16 with complicating pulmonary disorders (diffusing capacity of the lung for carbon monoxide (DLCO) and/or total lung capacity (TLC) < 70% predicted). The remaining 120 out of 175 constituted the study population. Dyspnoea following a 20% reduction in the baseline FEV1 (Dys20%) was linearly interpolated, using the rating of dyspnoea and the FEV1 at the two final concentrations of methacholine. In the 120 asthmatic subjects, the mean intensity of dyspnoea was "moderate" (2.9, SD 1.91; Borg 0-10) and the intensity across subjects was not significantly related to baseline FEV1, vital capacity (VC), FEV1/VC, DLCO, TLC and maximal static inspiratory pressure (MIP), alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370427 TI - Cardiac role in exercise limitation in asthmatic subjects with special reference to disease severity. AB - We wanted to assess limitations in cardiorespiratory fitness of asthmatic subjects, acclimatized to 1,300 m altitude and in a clinically stable state. We therefore studied 16 young asthmatic and 8 normal young subjects during an incremental bicycle exercise test. The asthmatics were divided into two groups, according to the Aas classification: a moderate asthma group (degree 2 and 3, no pulmonary impairment during symptom-free intervals), and a severe asthma group (degree 4 and 5, with persistent airway obstruction). The results showed that cardiorespiratory fitness is limited in severe asthmatic subjects acclimatized to an altitude of 1,300 m, due to decreased cardiac output and stroke volume. At submaximal exercise, the lower stroke volume is compensated by an increased arteriovenous oxygen content difference, but this compensation no longer exists at maximal exercise, which explains the lower maximal oxygen uptake in the severe asthma group. The hypothesis that the high tidal volume in the severe asthma group could lead to a decrease in left ventricular performance is considered. In conclusion, with respect to cardiorespiratory response to exercise, asthmatics should not be considered as a homogeneous group. Furthermore, relationship between ventilatory requirement and its consequences upon cardiac stroke volume provides a strong argument for the physical rehabilitation of asthmatics. Indeed, aerobic training can decrease the ventilation level for a given workload, and thus reduce inappropriate adaptations to exercise. PMID- 8370428 TI - Lack of short-term effect of the thromboxane synthetase inhibitor UK-38,485 on airway reactivity to methacholine in asthmatic subjects. AB - Previous open studies have suggested that thromboxane receptor antagonists or synthesis inhibitors lower airway hyperresponsiveness in human subjects. This would indicate a role of thromboxane A2 in the development or maintenance of hyperresponsiveness in asthma. Ten nonsmoking asthmatics (aged 23-64 yrs, 9 male) were included in a randomized, double-blind, placebo-controlled, cross-over study of the effect of one week of treatment with a potent selective thromboxane synthetase inhibitor (UK-38,485, 600 mg daily) on airway responsiveness. The study was preceded by a two week run-in period, and two weeks were used for wash out between the two trial periods. Adequacy of dosage and patient compliance was confirmed by a reduction in the ex vivo formation of thromboxane B2 (median concentration 3.22 micrograms.ml-1 after placebo, 0.10 microgram.ml-1 after UK 38,485, p < 0.05). The mean forced expiratory volume in one second (FEV1) after UK-38,485 was 2.55 l, compared to 2.56 l after treatment with placebo (p = 0.74). The geometric mean provocative dose of methacholine producing a 20% fall in FEV1 (PD20) before and after UK-38,485 was 23.9 and 32.2 micrograms, respectively, compared to 25.1 and 26.3 micrograms respectively, before and after placebo (p = 0.31). The results of this study suggest that thromboxane A2 does not play an important role in the maintenance of increased airway responsiveness in moderately severe asthmatics treated with low doses of inhaled steroids. PMID- 8370429 TI - Ba 679 Br, a new long-acting antimuscarinic bronchodilator: a pilot dose escalation study in COPD. AB - Preclinical studies with Ba 679 Br have demonstrated a significantly longer duration of action than ipratropium bromide. Following inhalation of single doses, no systemic antimuscarinic effects were noted at doses likely to be bronchodilating in man. The objective of the present pilot-study of Ba 679 Br was to establish the dose-range for its bronchodilatory activity in a small number of chronic obstructive pulmonary disease (COPD) patients, before initiating a formal dose- and time-response study. Employing an open cross-over design, the efficacy of Ba 679 Br was tested, following single inhalational administration of five doses of increasing magnitude on separate days in six patients with COPD. A piezoelectric crystal was used, in order to nebulize an aqueous solution into a mist suitable for inhalation. There was a mean increase in forced expiratory volume in one second (FEV1) of 36% 30 min after inhaling ipratropium bromide 40 micrograms. Pulmonary function tests (FEV1, and specific airways conductance (sGaw)) were performed, at regular time intervals up to 24 h after test drug inhalation. The bronchodilatory activity of Ba 679 Br appeared to be dose-related in the dose-range tested (10-160 micrograms). A peak response was reached in 1.5 2 h, and persisted for 10-15 h in the majority of patients with return to baseline FEV1 approximately 19 h after dosing. No changes in physical examination, electrocardiogram (ECG) and laboratory safety tests from predose values were noted, and no serious adverse events were reported by the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370430 TI - Pulmonary hypertension in childhood. AB - In the presence of pulmonary hypertension, the pulmonary vasculature fails to remodel after birth. Secondary changes then develop, and do so more rapidly than in the adult lung because the cells are exposed to the insult whilst still relatively undifferentiated. The commonest causes of pulmonary hypertension in newborn and young infants are alveolar hypoxia, and congenital heart disease causing a left-to-right shunt and increased pulmonary blood flow. The initial response of an increase in pulmonary arterial muscularity is common to both, but intimal proliferation can develop rapidly in those with complex congenital heart disease. The structural abnormalities are accompanied by abnormalities in the control of pulmonary vascular reactivity, a problem which is the focus of much current research activity. PMID- 8370431 TI - An evaluation of P0.1 measured in mouth and oesophagus, during carbon dioxide rebreathing in COPD. AB - The pressure generated 100 ms after the onset of an occluded inspiratory effort (P0.1) is advocated and used as a measure of respiratory centre drive. We have re examined P0.1, measured simultaneously in the mouth (Pmo0.1) and the oesophagus (Poes0.1), during carbon dioxide rebreathing, in eight patients with severe chronic obstructive pulmonary disease, to see whether either indicates central respiratory drive. Pmo0.1 was identical to Poes0.1 in 4 out of 61, greater than Poes0.1 in 18 out of 61, and less than Poes0.1 in 39 out of 61 measurements (overall Poes0.1-Pmo0.1, median +0.075, range -0.175 to +1.01 kPa). Within a rebreathing run in an individual patient, there was considerable variability in the relationship Pmo0.1/Poes0.1 (0.89 +/- 0.24), coefficient of variation (CoV%) 14.4 +/- 3.7%), in the end-expiratory oesophageal pressure (0.7 +/- 0.54 kPa, CoV% 105 +/- 106%), and in the time delay between the onset of a fall in oesophageal pressure (Poes) from the end-expiratory level to the beginning of inspiration, defined as starting when mouth pressure (Pmo) fell below atmospheric pressure (129 +/- 25 ms, CoV% 22.5 +/- 5.3%). We conclude that the problem of determining the true onset of inspiratory muscle activity from pressure data, and the likelihood that breaths are taken from different lung volumes, make it unlikely that Poes0.1 accurately represents central respiratory drive during rebreathing in chronic obstructive pulmonary disease. Furthermore, Pmo0.1 differed from Poes0.1 during rebreathing, and their relationship was not constant, so that Pmo0.1 is even less likely to be a useful reflection of central nervous system output or respiratory centre drive in such patients. PMID- 8370432 TI - Comparison of pressure and volume preset nasal ventilator systems in stable chronic respiratory failure. AB - Nasal intermittent positive pressure ventilation (NIPPV) has been widely used in the treatment of chronic respiratory disease. Ventilators may be volume or pressure preset; each type has theoretical advantages, but to date there has been no formal comparison. We wanted to assess the efficacy on blood gas changes that may be achieved and overall acceptability of four nasal ventilators (two pressure preset: Respironics bilevel positive airway pressure (BiPAP) and the Thomas NIPPY; and two volume preset: BromptonPac and Monnal-D) in patients with stable chronic respiratory failure. Median age was 59 yrs (range 48-71 yrs), mean (SD) arterial oxygen tension (PaO2) 7.16 (0.21) kPa, arterial carbon dioxide tension (PaCO2) 7.02 (0.35) kPa, forced expiratory volume in one second (FEV1) 0.76 (0.24) l, and forced vital capacity (FVC) 1.58 (0.49) l. All had previously used NIPPV. There were significant changes in blood gases at 2 h with each ventilator: mean change (95% confidence interval); BiPAP PaO2 +1.52 (0.95-2.09) kPa, PaCO2 1.04 (1.55-0.54) kPa; NIPPY PaO2 +1.63 (0.85-2.41) kPa, PaCO2, -1.1 (1.86-0.34) kPa; BromptonPac PaO2 +1.22 (0.75-1.67) kPa, PaCO2 -1.14 (1.52-0.76) kPa; Monnal D PaO2 +1.14 (0.42-1.84) kPa, PaCO2 -1.19 (2.14-0.23) kPa. Analysis of variance showed no significant differences in the efficacy of volume or pressure preset equipment, and all ventilators proved equally acceptable to the patients studied. We conclude that all four of the volume or pressure preset ventilators examined are suitable for the delivery of nasal intermittent positive pressure ventilation in patients with stable chronic respiratory failure. PMID- 8370434 TI - Bilateral pulmonary artery aneurysms in Behcet's disease. AB - A patient presented with fever, haemoptysis and large bilateral perihilar masses. Histology proved that these were pulmonary artery aneurysms due to pulmonary vasculitis, as a manifestation of Behcet's disease. It is suggested that a routine dynamic computed tomographic (CT) scan should be performed in the evaluation of such cases. PMID- 8370433 TI - Lesions of the arytenoid region in a patient with exertional dyspnoea. AB - A 63 year old woman presented with a 3 year history of exertional dyspnoea. Spirometry suggested extrathoracic airway obstruction (decreased inspiratory flow and saw-tooth pattern of flow-volume curves), and bronchoscopy revealed structural lesions and a trembling motion in the arytenoid region, causing upper airway obstruction on forced respiratory efforts. As there were no abnormal findings other than the lesions, the exertional dyspnoea was probably caused by impaired movement of the arytenoid region. PMID- 8370435 TI - Asymptomatic solitary papilloma of the bronchus: review of occurrence in Japan. AB - A case of solitary papilloma of the bronchus is described, and 15 other cases occurring in Japan are reviewed. A 57 year old asymptomatic male was referred to our hospital because many squamous metaplastic cells with moderate atypia were observed in sputum cytology, twice in 3 months. The chest X-ray showed no abnormal findings. Endoscopic examination revealed a polypoid tumour at the bifurcation of the right B6a and B6b. The tumour was removed completely by endoscopic biopsy, and histological findings showed squamous papilloma. There has been no evidence of recurrence for 3 yrs. We are not aware of a previously reported case of bronchial papilloma without symptoms or abnormal shadow on chest X-ray. Considering the fact that malignant change was reported in only one case in Japan, and that there is a possibility of cancer subsequently developing at another location in the lung which might also require resection, lobectomy should be avoided if the tumour can be removed completely through endoscopy. If the lesion is limited to a small area in the bronchus, conservative treatment such as photodynamic therapy and/or yttrium aluminium garnet (YAG) laser vaporization might be sufficient to obtain a complete cure. PMID- 8370436 TI - Changes in heart rate during obstructive sleep apnoea. PMID- 8370437 TI - Towards testing the Dutch hypothesis from childhood. PMID- 8370438 TI - Highlights on pulmonary hypertension: a commentary. PMID- 8370439 TI - Upper airway obstruction: the culprits are the arytenoids. PMID- 8370440 TI - Pulmonary involvement in Behcet's disease. PMID- 8370441 TI - Pulmonary involvement in human T-cell lymphotropic virus type-I uveitis: T lymphocytosis and high proviral DNA load in bronchoalveolar lavage fluid. AB - The ocular manifestation of human T-cell lymphotropic virus type I (HTLV-I) infection has been recognized as a new clinical entity termed HTLV-I uveitis. In order to determine whether HTLV-I uveitis is associated with lymphocyte alveolitis, bronchoalveolar lavage (BAL) was carried out in 11 patients with HTLV I uveitis, five asymptomatic HTLV-I carriers, 11 HTLV-I-negative patients with ocular sarcoidosis, and nine normal control subjects seronegative for HTLV-I. Six of the 11 patients with HTLV-I uveitis showed increased total cell counts, and T lymphocytosis in BAL fluid. CD4+/CD8+ ratios of T-lymphocytes were decreased in three of these patients, and normal in three other patients. Such abnormalities of the lung were not found in asymptomatic HTLV-I carriers, and in normal control subjects. BAL findings in HTLV-I uveitis differed from those of patients with sarcoidosis in terms of the lymphocytic component. Interestingly, it was found that there was an increase of HTLV-I proviral deoxyribonucleic acid (DNA) load in peripheral blood mononuclear cells (PBMC) from seven patients with HTLV-I uveitis, and in the BAL cells from four patients with pulmonary involvement. These results provide further evidence in terms of HTLV-I tropism for the lung, and suggest that a systemic and local increase of HTLV-I proviral DNA load plays an important role in the pathogenesis of lymphocyte alveolitis in patients with HTLV-I uveitis. PMID- 8370442 TI - IgG subclasses in the lungs of patients with interstitial pneumonitis following bone marrow transplantation. AB - Subclasses of immunoglobulin G (IgG) were measured in bronchoalveolar lavage (BAL) fluid and serum from five normal volunteers and 25 bone marrow transplant (BMT) recipients, who developed 32 episodes of pneumonitis. Evidence for local production of the four subclasses was sought, to assess whether any observed deficiency was associated with any particular group of pulmonary infections. In the normal volunteers, IgG1 and IgG4 could be detected in BAL fluid from all subjects, with evidence for local production of IgG1 in one, and IgG4 in all five. IgG2 could be detected in BAL fluid from one subject, but IgG3 was undetectable in all normal BAL fluid. The BMT recipients differed from the normal volunteers mainly in the presence of IgG2 and IgG3 in BAL fluid. Furthermore, IgG4 could not be detected in BAL from seven. Furthermore, IgG4 could not be detected in BAL from seven episodes of pneumonitis (six patients). Bacteria, protozoa or fungi alone were isolated from five of these seven lavages, whereas pneumonitis associated with these organisms alone only occurred in 9 of the remaining 25 episodes of pneumonitis (19 patients) where there was also evidence for local production of IgG4. Moreover, 4 out of 7 patients with no detectable IgG4 in lavage developed secondary infections, whilst only 5 out of 19 patients producing IgG4 locally developed secondary infections (p = 0.05). Although there was individual variation within each group, levels of local production of both IgG1 and IgG4 tended, however, to be higher in patients who died from pneumonitis than in those who recovered, suggesting that this may be a poor prognostic marker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370443 TI - Proliferating alveolar macrophages in BAL and lung function changes in interstitial lung disease. AB - In interstitial lung disease, the number of alveolar macrophages (AMs) can be increased. This may be caused by recruitment of precursor cells from peripheral blood and/or local proliferation in the lung. We therefore analysed proliferation, by studying both the expression of the nuclear proliferation antigen, Ki67, and the deoxyribonucleic acid (DNA) content, using the Feulgen reaction followed by cytometry. The patients had interstitial lung disease, i.e. sarcoidosis (n = 20), extrinsic allergic alveolitis (n = 20), idiopathic lung fibrosis or lung involvement in collagen-vascular disease (n = 19). In all patient groups there was a significant increase in proliferating AMs compared to healthy controls (4.2 versus 1.4% Feulgen, 2.1 versus 0.5% Ki67), with a significant correlation between these two parameters. A positive correlation was also found in bronchoalveolar lavage (BAL) between numbers of lymphocytes and proliferating cells in sarcoidosis and in fibrosis. In fibrosis, numbers of eosinophils and proliferating cells were also positively correlated. Our main finding was, however, a positive correlation between numbers of proliferating cells (Feulgen) and lung function parameters, especially vital capacity and oxygen tension (PO2) at rest, in patients with sarcoidosis and lung fibrosis. By contrast, in extrinsic allergic alveolitis, no correlation could be observed between proliferating cells and cell population or lung function. Our results suggest that local proliferation of macrophages is an important element in interstitial lung disease. PMID- 8370444 TI - Suppressive mechanisms of alveolar macrophages in interstitial lung diseases: role of soluble factors and cell-to-cell contact. AB - Alveolar macrophages (AMs) from patients with interstitial lung diseases, such as sarcoidosis and idiopathic pulmonary fibrosis, suppress the phytohaemagglutinin (PHA) stimulation of autologous peripheral lymphocytes. The aim of this study was to determine whether the suppressive effect of alveolar macrophages of patients with interstitial lung disease is due, not only to the secretion of soluble factors prostaglandin E2 (PGE2), interleukin-1 (IL-1) but is also correlated to a direct effect of AMs on the expression of IL-2 receptors (IL-2R: CD25) and on the induction of IL-2 activity. We studied 26 subjects, 8 with sarcoidosis, 7 with idiopathic pulmonary fibrosis, and 11 controls. Alveolar macrophages of sarcoid and idiopathic pulmonary fibrosis patients suppressed proliferation of autologous peripheral lymphocytes by 68 +/- 14% and 53 +/- 4.5%, respectively, compared to enhancement of 19 +/- 11% in three controls and suppression of 25 +/- 11% in the other six controls; the difference between subjects with interstitial lung disease and controls was significant. As already reported, the alveolar macrophages of sarcoid patients secreted large amounts of IL-1 (184 +/- 59 U.ml 1) whereas the alveolar macrophages from idiopathic pulmonary fibrosis patients secreted large amounts of PGE2 (3.6 +/- 2 ng.ml-1 x 10(-5) cells) compared with 23 +/- 19 U.ml-1 IL-1 and 0.34 +/- 0.15 ng.ml-1 x 10(-5) cells respectively, of controls. Suppression by supernatants recovered from lipopolysaccharide (LPS) stimulated alveolar macrophages can only partially explain the high suppressive effect of alveolar macrophages of interstitial lung diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370445 TI - The medical management of patients with cystic fibrosis following heart-lung transplantation. AB - Transplantation for end-stage respiratory failure in cystic fibrosis (CF), with encouraging medium-term results, is now possible. This paper details the postoperative medical treatment required by these patients. The management of 79 patients who underwent heart-lung transplantation is described. Details of intensive care, postoperative care, long-term follow-up, and the problems specific for cystic fibrosis patients are reported. The duration of care in the Intensive Care Unit (ICU) was 1-93 days (median 5 days). Intubation was required for 7 h to 93 days (median 48 h), and 11 patients required haemodiafiltration. High doses of cyclosporin A (mean 22 mg.kg-1 q.d.) were required. Acute rejection was common. There were 133 episodes of infection: bacterial 115, viral 11, and other organisms 7. Grand mal seizures occurred in 10 patients, lymphoproliferative disorders in 4, and obliterative bronchiolitis in 17. The median duration of hospital stay was 32 days. Despite having a multi-system disease, patients with CF can be successfully transplanted, if detailed attention is paid to their complex medical management. PMID- 8370446 TI - Surfactant inhibition by plasma proteins: differential sensitivity of various surfactant preparations. AB - Leakage of plasma proteins into the alveolar space may inhibit surfactant function. We compared the surface properties and the sensitivity to inhibitory proteins of different organic solvent surfactant extracts and a synthetic surfactant. Experiments were performed in the pulsating bubble surfactometer, with surfactant concentrations ranging between 0.1 and 2 mg.ml-1. Inhibition profiles towards fibrinogen, albumin and haemoglobin were obtained from calf lung surfactant extracts (CLSE), Alveofact, Curosurf and Survanta (all used in clinical, replacement studies in respiratory distress syndrome (RDS) and of an apoprotein-based synthetic phospholipid mixture (PLM-C/B; DPPC:PG:PA = 68.5:22.5:9, supplemented with 2% wt/wt non-palmitoylated human recombinant SP-C and 1% t/wt natural bovine SP-B). In the absence of inhibitory proteins, all surfactants exhibited dose-dependent rapid adsorption (rank order of relative efficacy PLM-C/B = CLSE > Alveofact > Curosurf > Survanta). Minimal surface tension was reduced to near zero values under dynamic compression (rank order PLM C/B > CLSE > Alveofact = Curosurf) and to approximately 4 mN.m-1 (Survanta). Curosurf and Survanta were dose-dependently inhibited by fibrinogen > haemoglobin > albumin, with far-reaching loss of surface activity at protein-surfactant ratios above 1:1. In contrast, CLSE and Alveofact were only moderately inhibited by fibrinogen, and were not affected by haemoglobin and albumin, up to protein surfactant ratios of 2:1. PLM-C/B exhibited resistance to fibrinogen, intermediate sensitivity to albumin, and was severely inhibited by haemoglobin. We conclude that various natural surfactant extracts and an apoprotein-based synthetic surfactant mixture markedly differ in their sensitivity to inhibitory plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370447 TI - The contribution of respiratory function tests to clinical diagnosis. AB - The purpose of this study was to investigate the amount of diagnostic information contained in a set of routine lung function studies and to attempt to determine which tests could be omitted without significant loss of discrimination. Cluster analysis was performed on a set of physiological and questionnaire data, collected prospectively in 1,542 male patients, referred consecutively for measurement of forced expired volumes, static lung volumes and measurements of the transfer factor for carbon monoxide. A respiratory questionnaire was completed for each patient. A physician assigned the patients to a rigorously defined diagnostic category, based on supporting clinical information, as well as pulmonary function, apart from 241 patients with unusual diagnoses and those in whom the criteria did not apply satisfactorily. This diagnosis was never included as a classification variable. Basing the classification on three independent measurements, total lung capacity, the ratio of forced expiratory volume in one second (FEV1) to vital capacity, and the transfer factor for carbon monoxide, the computer generated six groups: one normal, one showing an isolated gas exchange defect, and four with varying degrees of restriction and obstruction. This classification performed well in separating the patients with the clinical diagnoses of chronic airflow obstruction, bronchial asthma and interstitial lung disease from those with ischaemic and valvular heart disease and other miscellaneous disorders. Omitting total lung capacity resulted in some loss of specificity, but valid information was still obtained. The inclusion of all the static and dynamic lung volumes and of carbon monoxide transfer coefficient made little difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370448 TI - Tracheal size is a determinant of the bronchoconstrictive response to inhaled methacholine. AB - We hypothesized that the size of the large airways is a determinant of bronchial responsiveness to inhaled methacholine. This was investigated by measuring the relationship of tracheal size and branching angle to the bronchoconstrictive response to methacholine, in 169 male construction insulators, aged 20-50 yrs, as part of a workforce-based, cross-sectional survey of respiratory health. Bronchial responsiveness was expressed as the concentration of methacholine, inhaled for 2 min of tidal breathing, which provoked a 15% fall in forced expiratory volume in one second (FEV1). Tracheal size was assessed from tracings of standard posteroanterior chest radiographs, at full inspiration. After accounting for the effect of airway calibre (FEV1/forced vital capacity (FVC)), age, height, and pack-years of cigarette smoking, on airways responsiveness, there was a significant association (p < 0.05) between tracheal length, diameter, or surface area and the degree of bronchoconstriction obtained by inhaling methacholine. The increase in airway responsiveness with decreasing tracheal size may reflect increased deposition of methacholine, secondary to smaller cross sectional area and greater linear velocity of air in the trachea and main bronchi. PMID- 8370449 TI - Accuracy and sensitivity of the interrupter technique for measuring the response to bronchial challenge in normal subjects. AB - The interrupter technique is a non-invasive method for measuring airway calibre. Since the calculation of interrupter resistance (Rint) is critically dependent upon the analysis of the mouth pressure/time (Pmo(t)) curve obtained after flow interruption, we wanted to assess the relative merits of four different analyses of Pmo(t) curves, obtained under basal conditions and following methacholine induced airway narrowing, in 10 healthy adults. Four methods of analysing the Pmo(t) curves were used to calculate Rint values: RintC-a smooth curve fit with back-extrapolation; RintL-two-point linear fit with back-extrapolation; RintEO calculated from the pressure change after the post-interruption oscillations had decayed (end-oscillation); and RintEI-calculated from the pressure change at the end of the period of interruption. The airway response measured with the four Rint methods was compared with plethysmographic airway resistance (Raw). The sensitivity of the methods was determined by calculating a sensitivity index (SI), the change in resistance after challenge expressed in multiples of baseline standard deviation. Values of RintC were similar to Raw values under all conditions. Resistance values from the remaining Rint methods significantly exceeded Raw (mean basal difference: 0.13-0.34 kPa.l-1 x s; mean difference after challenge: 0.12-0.42 kPa.l-1 x s. Raw was the most sensitive method for detecting bronchoconstriction (doubling of Raw was equivalent to SI of 10.5). Of the Rint methods, RintEI gave the highest sensitivity index (SI = 3.1), with a 42% mean change; RintC produced the greatest proportionate change after challenge (55%), but with a lower SI (2.2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370450 TI - Kin recognition. A model for the retention of Golgi enzymes. AB - The surprising result that the spanning domain causes retention of proteins in the Golgi stack poses the question as to the actual mechanism. Here we present a simple model that might have general applicability. PMID- 8370451 TI - Observation of inter-subunit nuclear Overhauser effects in a dimeric protein. Application to the Arc repressor. AB - For the structure determination of symmetric protein dimers it is necessary to distinguish between intra- and inter-subunit NOEs. A method is presented to measure selectively the inter-subunit NOEs using uniform 15N and 13C isotope labelling. This is accomplished by double filtered 2D NOE experiments on mixtures of native protein with isotope-labeled protein. The method has been applied to the Arc repressor and allows the characterization of virtually all proton-proton NOEs in terms of their intra- or inter-subunit nature. PMID- 8370452 TI - Mammalian calponin. Identification and expression of genetic variants. AB - Calponin is a smooth muscle specific, actin-, tropomyosin- and calmodulin-binding protein thought to be involved in some way in the regulation or modulation of contraction. Here we describe the cloning and bacterial expression of two calponin species from murine and porcine smooth muscle tissues. Primary and secondary structural analyses of the deduced amino acid sequences revealed a high degree of homology to avian calponin with the exception of a short and variable C terminal segment. The sequence data demonstrate that the two mammalian calponin variants do not arise via alternative splicing but are encoded by different genes. PMID- 8370453 TI - Biosynthesis and secretion of a precursor of nisin Z by Lactococcus lactis, directed by the leader peptide of the homologous lantibiotic subtilin from Bacillus subtilis. AB - The DNA sequence encoding the leader peptide of the lantibiotic subtilin from Bacillus subtilis was fused to the sequence encoding pronisin Z, and this hybrid gene was expressed in a Lactococcus lactis strain that produces nisin A. This strain simultaneously secreted nisin A and a protein of approximately 6 kDa. Amino acid sequencing of the purified 6 kDa protein and structural analysis of its main tryptic fragment by two-dimensional 1H-NMR showed that it consists of the unmodified leader peptide of subtilin, without the N-terminal methionine residue, linked to a fully matured nisin Z part. The hybrid protein and its main tryptic fragment [ITPQ]-nisin Z, showed at least 200-fold lower antimicrobial activities than nisin Z against three different indicator strains. PMID- 8370454 TI - Methylglyoxal and the polyol pathway. Three-carbon compounds are substrates for sheep liver sorbitol dehydrogenase. AB - Methylglyoxal, 1,2-propanediol and glycerol are shown to be substrates for sheep liver sorbitol dehydrogenase. With 1,2-propanediol the enzyme-catalyzed reaction occurs specifically with the R(-)-enantiomer. The maximum velocities and the specificity constants obtained for the three-carbon substrates are considerably lower than those reported previously for sorbitol, and suggest that rate determination is imposed by catalytic steps other than the enzyme-coenzyme product dissociation. The present findings are discussed in terms of substrate specificity and stereospecificity, and may indicate novel aspects of sorbitol dehydrogenase function in relation to glucose metabolism and diabetic pathogenesis. PMID- 8370455 TI - Purification of an UDP-glucose:flavone, 7-O-glucosyltransferase, from Silene latifolia using a specific interaction between the enzyme and phenyl-Sepharose. AB - An UDP-glucose:flavonoid, 7-O-glucosyltransferase, from Silene latifolia was isolated from petals and purified 450-fold using a combination of gel-filtration, affinity chromatography and anion-exchange chromatography. Affinity chromatography on a phenyl-Sepharose CL-4B column in combination with elution with the substrate, isovitexin (6-C-glucosylapigenin), was an especially effective purification step. A purification factor between 10 and 20 could be reached using this column. A possible mechanism for the specific interaction of the enzyme with the phenyl-Sepharose will be discussed. This method of purification may also be applicable to other enzymes which use aromatic compounds as substrates. On a SDS-PAGE gel a band of 54 kDa, which co-purified with enzyme activity, could be detected in the purest fraction. PMID- 8370456 TI - Ribosomal proteins, TL4 and TL5, from Thermus thermophilus form hybrid complexes with 5 S ribosomal RNA from different microorganisms. AB - Hybrid complexes of the ribosomal proteins, TL4 and TL5, from Thermus thermophilus with 5 S ribosomal RNA from Escherichia coli and Bacillus stearothermophilus have been prepared. There was no competition between the two proteins for the binding sites. Stoichiometry of 5 S RNA binding for both proteins was 1:1 (protein/RNA). The TL4 protein competed with the E. coli ribosomal L5 protein, and the TL5 protein competed with the E. coli ribosomal proteins, L18 and L25, for binding with 5 S RNA. PMID- 8370457 TI - beta-Amyloid protein enhances the mitogen-induced calcium response in circulating human lymphocytes. AB - The role of beta-amyloid in Alzheimer's disease and its cellular mechanism of action on neurons are still unclear. There is growing evidence that beta-amyloid or its fragment, 25-35, influence neuronal calcium regulation. To investigate the effects of beta-amyloid on calcium homeostasis in man we used peripheral human lymphocytes as a model system for central neurons. beta-Amyloid fragment 25-35 exposed to lymphocytes for 60 s elevates the phytohemagglutinin (PHA)-induced Ca2+ rise in a dose-dependent manner. Small effects were already seen at concentrations as low as 50 nmol/l. Similar effects were also observed with fragment 1-40, whereas fragments 1-28 or 12-28 did not affect the Ca2+ response after PHA stimulation. Our findings support the hypothesis of an enhanced calcium response as a general feature of beta-amyloid's neurotoxicity. The lymphocyte seems to be a valuable model to study this effect in man. PMID- 8370458 TI - Excitonic interactions in the light-harvesting antenna of photosynthetic purple bacteria and their influence on picosecond absorbance difference spectra. AB - A new model of the light-harvesting antenna (core complex) of purple photosynthetic bacteria is proposed based on excitonic interactions in circular aggregates of bacteriochlorophyll molecules. The calculated absorbance difference spectra of circular aggregates demonstrate all special features observed in the experimental spectra of purple bacteria. In particular, the absorption changes with high amplitude of bleaching at the long-wavelength side of the absorption band at different excitation energy are predicted. PMID- 8370459 TI - Tamoxifen and related compounds decrease membrane fluidity in liposomes. Mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions? AB - Tamoxifen and related compounds decrease membrane fluidity in ox-brain phospholipid liposomes: their order of effectiveness is, 4-hydroxytamoxifen > 17 beta-oestradiol > tamoxifen > cis-tamoxifen > N-desmethyltamoxifen > cholesterol. A good positive correlation was demonstrated between the decrease in membrane fluidity by these compounds and their antioxidant ability as inhibitors of liposomal and microsomal lipid peroxidation (correlation coefficient, r = 0.99, P < 0.001, in both cases). The ability of tamoxifen to decrease membrane fluidity is suggested to be the mechanism of its antioxidant action and is discussed in relation to its anticancer and cardioprotective actions. PMID- 8370460 TI - A plasma-membrane progesterone receptor in human sperm is switched on by increasing intracellular free calcium. AB - Recent studies have revealed the presence of an atypical progesterone receptor on the plasma membrane of a relatively small subpopulation of human sperm cells. In this study, we show that the receptor is present in many cells in a latent form and that the receptor function in these cells is switched on asynchronously by increasing intracellular free Ca2+ levels. Under physiological conditions, this process occurs during sperm capacitation, but it can be mimicked by a short sperm exposure to the Ca(2+)-mobilizing agent thapsigargin. These observations suggest a role of Ca2+ as a modulator of nongenomic steroid effects on the cell surface. PMID- 8370461 TI - Efficient processing and export of human growth hormone by heat labile enterotoxin chain B signal sequence. AB - The heat-labile enterotoxin chain B (LTB) signal sequence was used for the processing and export of human growth hormone (hGH). The protein was completely processed and exported across the cell membrane to accumulate in the periplasmic space in Escherichia coli. The human growth hormone cDNA was cloned as a PCR amplified fragment under the control of tac promoter and translationally fused to the LTB signal sequence. The rate of processing of hGH under the control of the LTB signal sequence was equal to or more than the rate of induction of expression, indicating efficient processing. The receptor binding activity of the processed periplasmic protein was established in a radio receptor assay. PMID- 8370462 TI - Identification of MIM23, a putative component of the protein import machinery of the mitochondrial inner membrane. AB - A screening for yeast mutants impaired in mitochondrial protein import led to the identification of two genes (MPII and MPI2) encoding the essential components MIM44 and MIM17 of the inner membrane import machinery. We analyzed twelve additional mutants obtained in the screening and found two further complementation groups. One group represents mutants of SSC1, the gene encoding mitochondrial hsp70, an essential matrix protein required for protein import across the inner membrane. The second complementation group represents mutants of a new gene (MP13) encoding a 23 kDa integral inner membrane protein (MIM23). MIM23 is synthesized without a presequence, and its import to the inner membrane requires a membrane potential. MIM23 contains a domain homologous to half of MIM17. We speculate that MIM23 is a new member of the protein import machinery of the mitochondrial inner membrane. PMID- 8370463 TI - Phospholipid asymmetry of the outer membrane of rat liver mitochondria. Evidence for the presence of cardiolipin on the outside of the outer membrane. AB - The phospholipid topology of the outer membrane of intact rat liver mitochondria and derived outer membrane vesicles was investigated by determining the accessible pool of the various phospholipid classes towards phospholipase A2, a phosphatidylcholine-specific transfer protein and by chemical labeling using trinitrobenzene sulfonic acid. The outer membrane vesicles are sealed and have a right-side-out topology with a proposed localization of 55%, 77%, 100%, and at least 30% of the phosphatidylcholine, phosphatidylethanolamine, cardiolipin, and phosphatidylinositol plus phosphatidylserine in the outer leaflet, respectively. The outer membrane in intact mitochondria appears to have a similar phospholipid distribution. PMID- 8370464 TI - Storage of saposins A and D in infantile neuronal ceroid-lipofuscinosis. AB - We have isolated storage cytosomes from brain tissue of patients with infantile neuronal ceroid-lipofuscinosis. The purified storage bodies were subjected to compositional analysis which revealed a high content of proteins, accounting for 43% of dry weight. Saposins A and D, also known as sphingolipid activator proteins (SAPs), were shown to constitute a major portion of the accumulated protein using gel electrophoresis and sequence analysis. This is the first time that saposins have been found to be stored in any form of neuronal ceroid lipofuscinosis. PMID- 8370465 TI - Enhancement by retinoid of hemin-induced differentiation of human leukemia K562 cell line. AB - The effect of retinoid on human leukemia K562 cell differentiation induced by hemin was examined. Retinoids (retinoic acid and synthetic retinoids [Am80 and Ch55]) dose-dependently enhanced hemin-induced erythroid differentiation of K562 cells, though these retinoids themselves did not induce the differentiation. Under optimal conditions, these retinoids caused a doubling of the population of hemin-induced differentiated cells. In addition, co-treatment of cells with hemin and retinoid led to longer maintenance of the differentiated state after the removal of hemin, which might imply acquisition of irreversibility of hemin induced differentiation. These results suggest that the combination of retinoids with other differentiation inducers might be useful for leukemia therapy in cases where the leukemic cells are poorly responsive or unresponsive to retinoids, alone. PMID- 8370466 TI - Cooperative homodimeric hemoglobin from Scapharca inaequivalvis. cDNA cloning and expression of the fully functional protein in E. coli. AB - The overexpression of the fully functional, cooperative homodimeric hemoglobin of the bivalve mollusc, Scapharca inaequivalvis, has been accomplished in E. coli from its cDNA. The latter was isolated by PCR amplification of total RNA and sequenced. The cDNA-derived sequence differed by a single amino acid when compared to that previously obtained from purified protein. Interest in this hemoglobin resides in the unique assemblage of the two identical subunits, with the heme groups facing each other in the inside of the molecule, opposite to that occurring in vertebrate hemoglobins. The results presented here are the basis for future studies of structure/function relationships by site directed mutagenesis. PMID- 8370467 TI - Uridylylation of the PII protein in Rhizobium leguminosarum. AB - Permeabilization with cetyl trimethyl ammonium bromide was used to study the post translational modification of the PII protein in Rhizobium leguminosarum. Upon incubation with radioactive UTP a single band was obtained after SDS-PAGE and autoradiography. RNase resistance and snake venom phosphodiesterase sensitivity showed that radioactivity was bound through a phosphodiester bond to a protein which was absorbed by an antiserum specific for the PII protein. Uridylylation of the PII protein was shown to be dependent on the modifications of the glutamine/alpha-ketoglutarate ratio. PMID- 8370468 TI - The cyanobacterium, Synechococcus sp. PCC7942, possesses two distinct genes encoding cation-transporting P-type ATPases. AB - P-type (or E1 E2-type) ATPases comprise a large family of prokaryotic and eukaryotic proteins capable of transporting a variety of cations, and function in a wide variety of cellular processes. The present study was carried out to search for genes encoding P-type ATPases in the phototrophic cyanobacterium, Synechococcus sp. PCC7942. We succeeded in cloning two genes each encoding P-type ATPases from this bacterium. It was found that Synechococcus at least, two distinct P-type ATPases; one belongs to the family of typical prokaryotic P-type ATPases and the other markedly resembles eukaryotic P-type ATPases. An insertion mutant lacking either of these two ATPase-genes was constructed. The results showed that the growth of these mutants is hypersensitive to osmotic stress upon addition of NaCl or sorbitol to the medium. PMID- 8370469 TI - Intracellular parasitism of Legionella and signaling in eukaryotic cells. AB - In this review the phenomenon of antibacterial activity of phagocytes and its relationship to the general system of signal transduction in eukaryotic cells is examined. Data are reviewed that support the hypothesis that interference in transduction of regulatory signals during microbial invasion could be caused by specific bacterial products and lead to an inadequate bactericidal response, and hence multiplication of the bacteria in a host. In this connection, information concerning virulence factors of the facultative intracellular parasite Legionella is discussed. PMID- 8370470 TI - Bacterial bioluminescence: organization, regulation, and application of the lux genes. AB - Significant advances have been made in the characterization of luciferases and other lux-specific proteins as well as the lux genes from a number of different species of marine and terrestrial luminescent bacteria. A common lux gene organization (luxCDAB..E) modulated by the presence of specific genes involved in regulation and flavin binding and metabolism (luxF-I,L,R,Y) has been found with the luciferase genes (luxAB) flanked by the genes involved in synthesis of its fatty aldehyde substrate (luxCDE). For many species, light intensity per cell is highly dependent on cellular growth resulting in a spectacular autoinduction of luminescence at high cell density. Consequently, the bacterial lux system is of particular interest as it can serve as an excellent model for more general signal transduction systems involved in developmental processes, intercellular communication, and even symbioses. Identification of the lux autoinducers and regulatory proteins of Vibrio harveyi and Vibrio fischeri has provided the biochemical and genetic basis for dissection of the luminescent system. Isolation of the lux genes and the ability to transfer these genes into prokaryotic and eukaryotic organisms have greatly expanded the scope and potential uses of bacterial bioluminescence as a safe, rapid, and sensitive sensor for a wide variety of compounds and metabolic processes. PMID- 8370471 TI - Integral membrane heparan sulfate proteoglycans. AB - Heparan sulfate is a regulatory polysaccharide. It modulates specific growth factor-receptor interactions, accelerates the formation of specific proteinase proteinase inhibitor complexes, and mediates interactions of the cell surface with several enzymes and structural proteins. It abounds on the surfaces of embryonic cells, respecting or outlining morphogenetic rather than histological boundaries. This cell surface-associated heparan sulfate is implanted on specific integral membrane proteins, which together constitute two novel molecular families. The first family includes four syndecan-like integral membrane proteoglycans (SLIPS), with core proteins that span the membrane and shared sequence motifs in highly conserved cytoplasmic domains. The second is made up by two or more glypican-related integral membrane proteoglycans (GRIPS) that are linked to the cell surface via glycosyl phosphatidylinositol. These proteoglycans show differential expression and turnover patterns, prevailing in distinct cell types, membrane domains, and endocytotic machineries, and are subject to strict developmental controls. This suggests that each of these cell surface proteoglycans functions in a specific context, and that these functions pertain to the transduction of signals that emanate from the continuous interplay between matrix components, growth factors, and proteinases. Caution: beware of loose GRIPS and SLIPS on unsteady cell surfaces. PMID- 8370472 TI - Pericyte physiology. AB - Endothelial cells are the primary physical barrier between blood and tissue in microvessels. The other capillary and post-capillary venule wall cell is the pericyte. The literature on the biology of endothelium is appreciable but less is known about pericytes. Pericytes are morphologically, biochemically, and physiologically heterogeneous. Some of pericyte functional characteristics observed in vivo and in vitro are that they: regulate endothelial proliferation and differentiation; contract in manners that either exacerbate or stem endothelial cell junctional inflammatory leakage; function as a progenitor cell; synthesize and secrete a wide variety of vasoactive autoregulating agonists; synthesize and release structural constituents of the basement membrane and extracellular matrix. Pericytes are also involved in specific microvascular diseases. This review focuses principally on nonmesangial pericytes and specific activities such as the posttranslational, short-term responses that affect microvascular perfusion and permeability, and on pericyte-endothelial cell interaction. PMID- 8370473 TI - Regulation of the long-chain carnitine acyltransferases. AB - Long-chain carnitine acyltransferases are a family of enzymes found in mitochondria, peroxisomes, and endoplasmic reticulum that catalyze the exchange of carnitine for coenzyme A in the fatty acyl-CoA. Conversion of the fatty acyl CoA to fatty acylcarnitine renders the fatty acid more permeable to the various cellular membranes. The mitochondrial carnitine palmitoyltransferases are considered important in the regulation of mitochondrial beta-oxidation of long chain fatty acids. However, palmitoylcarnitine produced by peroxisomal carnitine octanoyltransferase or by microsomal carnitine palmitoyltransferase is not different from that produced by the mitochondrial enzyme. Therefore, for there to be control of fatty acid oxidation by the long-chain carnitine acyltransferases, there would have to be some mechanism to coordinately regulate these varied enzymes. The first system of regulation involves inhibition by malonyl-CoA, an intermediate in the synthesis of fatty acids. Malonyl-CoA inhibits long-chain carnitine acyltransferase activity by all three enzymes at similar concentrations in the physiological range. In addition, the mitochondrial and peroxisomal enzymes are known to be regulated at the level of mRNA transcription by a number of shared factors. Although the microsomal enzyme is less well studied, there does, indeed, appear to be a pattern of coordinate regulation for this system. PMID- 8370474 TI - Nicotine inhibition of apoptosis suggests a role in tumor promotion. AB - Recent evidence indicates that cell death through apoptosis may be an important mechanism to prevent tumor development. Therefore, agents that inhibit apoptosis may function as tumor promoters. The purpose of this study was to determine the effects of nicotine on the process of apoptosis. The results demonstrate that nicotine inhibits apoptosis induced by diverse stimuli including tumor necrosis factor (TNF), UV light, chemotherapeutic drugs, and calcium ionophore. This phenomenon was observed in normal and transformed cells derived from a variety of species and tissues, including tumor cell types related to tobacco use. The major nicotine metabolite, cotinine, also inhibited apoptosis, whereas N nitrosodiethylamine, a carcinogen found in tobacco, was without effect. Therefore, nicotine-mediated inhibition of apoptosis may contribute to the pathogenesis of tobacco-related cancer as well as decrease the efficacy of cancer therapies. PMID- 8370475 TI - Seasonal variations in antibody-dependent cellular cytotoxicity regulation by melatonin. AB - Data collected over a period of 4 years show that melatonin (two daily i.v. injections of 0.1 mg/kg body wt. given at 16:00 h) was able to enhance antibody dependent cellular cytotoxicity (ADCC) in summer, but not in winter. Dose response curves carried out in January, May, July, and October suggest that the seasonal effects reported are related to differences in the sensitivity of mice to melatonin during the course of the year. These results show seasonal variations in the immune modulatory action of melatonin. PMID- 8370476 TI - Somatostatin analog lanreotide inhibits myocyte replication and several growth factors in allograft arteriosclerosis. AB - Chronic rejection is the most common reason for late loss of a transplant. The molecular mechanism of chronic rejection is not known and there is no treatment for this disorder. The characteristic histological feature in chronic rejection is increased smooth muscle cell replication in the vascular wall, leading to allograft arteriosclerosis. In this study we demonstrate that nonimmunosuppressed rat aortic allografts undergoing chronic rejection synthesize increased quantities of several smooth muscle cell growth-promoting substances in the vascular wall including interleukin-1, eicosanoids, and several peptide growth factors. Administration of a stable somatostatin analog lanreotide, BIM 23014, strongly inhibits myocyte proliferation in the allograft in vivo. It has no inhibitory effect on the proliferation of smooth muscle cells in vitro. Concomitantly, the locally produced peptide growth factors, i.e., epidermal growth factor, insulin-like growth factor 1, and BB-isomer of platelet-derived growth factor, but not other mediators of inflammation, are significantly reduced. The results suggest that growth factors are the main effector molecules leading to myocyte proliferation in allograft arteriosclerosis and that allograft arteriosclerosis (chronic rejection) may be specifically inhibited by lanreotide administration. PMID- 8370477 TI - Microencapsulation of recombinant cells: a new delivery system for gene therapy. AB - The therapeutic potential of somatic gene therapy has been extensively investigated in recent years, yet its slow progression into the clinical setting can be attributed to problems associated with the inability to achieve efficient gene transfers, to obtain sustained level of expression of the transfected gene, and the necessity to avoid immunorejection after transplantation. Here we report on an alternate strategy in gene therapy that overcomes all three problems by immunoisolating genetically modified cells in a biocompatible membrane, thereby introducing a system that can provide sustained delivery of the desired gene product. As a model, mouse fibroblasts transformed with the human growth hormone gene (Ltk-GH) were encapsulated with an alginate-poly-L-lysine-alginate membrane. Long-term in vitro studies showed that the encapsulation of the cells was physiologically compatible with growth and survival of the cells. Furthermore, there was a unique pattern of secretion of the human protein by the encapsulated cells: there was a phase of steady increase in the secretion of the human growth hormone by each cell, followed by a plateau phase. The most convincing evidence of the feasibility of this strategy was provided by the in vivo study: Balb-c mice transplanted with encapsulated Ltk-GH cells had detectable serum levels of human growth hormone (hGH) for the duration of the study (115 days). Moreover, encapsulated cells recovered from a recipient 1 year after the transplantation continued to secrete high levels of hGH in culture. PMID- 8370478 TI - Intracellular diversion of glycoprotein GP160 of human immunodeficiency virus to lysosomes as a strategy of AIDS gene therapy. AB - A potential gene therapy strategy against human immunodeficiency virus (HIV-1) is to disrupt the intracellular transport of viral proteins. We report here the binding and transporting of HIV-1 glycoprotein gp160 to lysosomes as a result of the expression of fusion genes consisting of soluble CD4 and lysosome targeting domains. The effective lysosome targeting domain tested includes a lysosomal protease zymogen, procathepsin D, and the COOH-terminal domains of three lysosome membrane proteins: lamp-1, lamp-2, and lysosomal acid phosphatase. We demonstrated that cell fusion (syncytium), caused by the transport of gp160 to the surface of HeLa-CD4+ cells, was completely abolished by the expression of these fusion genes. The lysosomal localization of gp160 in HeLa cells coexpressing CD4-fusion genes was also established. From pulse-chase experiments, we observed that gp160 and the fusion proteins were degraded, as expected of lysosomal activities. Additionally, T lymphoblastoid cells transiently and permanently expressing these fusion genes strongly retarded the propagation of human immunodeficiency virus type 1. Thus, these fusion genes can deprive HIV of newly synthesized envelope protein gp160 for the assembly of new virions and are potentially useful in gene therapy against AIDS. PMID- 8370479 TI - Regulation of the phosphoenolpyruvate carboxykinase/human factor IX gene introduced into the livers of adult rats by receptor-mediated gene transfer. AB - Gene transfer systems targeting the asialoglycoprotein receptor have been developed to introduce functional genes into cells in culture and livers of intact animals. A synthetic neoglycoprotein carrier was constructed and complexed to a chimeric gene containing the cDNA for human factor IX ligated to the promoter-regulatory region of the gene for phosphoenolpyruvate carboxykinase from the rat. The complex was used to transfect human hepatoma cells that express the asialoglycoprotein receptor. Human factor IX DNA sequences were found in cells 10 days after treatment. A 1.4 kB mRNA transcript was detected by Northern blot hybridization, which was inducible by treatment with dexamethasone or cAMP with theophylline. Western blot hybridization of proteins secreted into the culture medium detected human factor IX. The chimeric gene was also transferred into livers of rats using the neoglycoprotein carrier system after partial hepatectomy. Although the results were variable, the exogenous gene was transcribed in livers of several animals, and maximal levels of expression of the fully processed human factor IX were detected 30 days after introduction. The concentration of factor IX in the blood returned to control levels 60 days after transfection. Factor IX production was induced as late as 96 days after treatment by feeding transfected animals a diet high in protein but devoid of carbohydrates. This DNA carrier system can be used to introduce functional genes into the livers of rats, and may be a useful technique for gene therapy targeting the liver. PMID- 8370480 TI - Autoimmune diabetes results from genetic defects manifest by antigen presenting cells. AB - In most cases, insulin-dependent diabetes results from autoimmune elimination of pancreatic beta cells by T lymphocytes that are generated as a result of complex polygenic interactions between particular MHC haplotypes and non-MHC linked susceptibility modifiers. Immature T cells with potential autoreactivity are normally destroyed in the thymus when they are highly activated after ligation of the T cell receptor (TCR) with "self" peptides bound to MHC molecules on antigen presenting cells (APC) such as macrophages. Here the hypothesis is put forth that non-MHC linked diabetes susceptibility genes contribute to subtle defects in the maturation of macrophages, and in synergy with a diabetogenic MHC haplotype generate APC that are unable to trigger autoreactive T cells to an activation state high enough to induce their destruction. PMID- 8370482 TI - Science odyssey: bringing our schools aboard. PMID- 8370481 TI - Basic medical sciences and research 50 years ago. PMID- 8370483 TI - Extracellular matrix. 2: Role of extracellular matrix molecules and their receptors in the nervous system. AB - Extracellular matrix molecules help regulate many aspects of neural development, including survival, migration, axon growth, and synapse formation by neurons. These same molecules have been shown to modulate regeneration of neurons after injuries. They also regulate the development and differentiation of other neural cells, such as astroglia and Schwann cells. Significant progress has been made recently in characterizing both ECM constituents and their receptors in the nervous system. Extracellular matrix molecules promote cell adhesion, activate intracellular signaling pathways, and modulate the activities of several growth factors and proteins. Our current understanding of the extracellular matrix, its receptors, and its functions in the nervous system are discussed. PMID- 8370484 TI - [Legal determination of physician's professional role exemplified by the abortion problem]. PMID- 8370485 TI - [D-dimer and plasminogen activator of the urokinase type: personal experiences with breast cancer]. AB - Plasma values of d-dimer, a stable end product of plasmin-induced fibrinolysis, were ascertained in 128 female patients with mammary carcinoma. These patients demonstrated significantly increased d-dimers in comparison with the control group with benign mammary disease (p < 0.01). The sensitivity and specificity of d-dimer were slightly higher than those of the established tumour marker CA 15-3 and CEA. There was no correlation between d-dimers in the plasma and increased expression of urokinase plasminogen activator (UPA) in the tissue. Increased d dimers in the plasma of female patients with mammary carcinoma reflect multi factoral interactions between carcinoma growth and the haemostatic-fibrinolytic system, and may be used as tumour markers. PMID- 8370486 TI - [Immunohistochemical detection of EGF-receptors in breast cancers]. AB - We examined the possibility of a quick and easy-to-perform way to determine the EGF receptor status in primary breast cancer cells by immunohistochemical staining. For this, we used two different monoclonal antibodies on corresponding tissue slides (Gullick, London; Mendelsohn, New York). The staining was interpreted by a semiquantitative histoscore. With both antibodies, we were able to detect EGF-R in breast tumours. We examined 80 tumours. 15 respectively 21% were EGF-R rich. 25% of the tumours were classified EGF-R poor. In 64 (54%) we were not able to detect EGF-R. The judgement of the EGF-R status by the different antibodies was identical in 80%. The results were also compared with the oestrogen receptor status (ER). We did not find a significant accumulation of EGF R positive tissues in the group of ER-negative tumours (11/28 respectively 16/32). Nevertheless most ER-positive tumours showed a negative EGF-R receptor score (32/52; 27/48). These results are comparable to the studies of the Sainsbury group. In addition we compared the EGF-R of our tumours also with other parameters for the prognosis of breast cancer such as lymph node status, histological grading and menopausal status. We found, that nearly two thirds of the EGF-R negative tumours were lymph node negative. Only 18% of the lymph node negative tumours had a positive EGF-R status in both techniques. The results of immunohistochemical staining were also compared with a radio-receptor assay. The results were identical in 85% of the cases. PMID- 8370487 TI - [Surgical treatment of recurrent stress incontinence: Burch versus lyodura sling operation--a prospective study]. AB - This prospective randomised study involved 52 female patients suffering from recurrent stress urinary incontinence, objectively confirmed by means of clinical incontinence tests and urodynamic examinations. They alternatively underwent colposuspension according to Burch or suburethral sling procedure surgery. Urodynamic and sonographic examinations were carried out before and 2.5 years (i.e. within a range of 2-3) after surgery according to Burch or suburethral sling procedure. There was no significant difference between the two methods with respect to subjective and objective rate of cure, which amounted to 85% of the cases involving colposuspension and 88% of cases involving the suburethral sling procedure. Both methods resulted in a significant improvement of the depression quotient and a significant elevation of the internal urethral meatus (p < 0.05). Apart from an aggravation of urge symptoms in both groups, the patients with surgery according to Burch tended towards enterocele and rectocele in the medium range, whereas urination disorders had to be accepted in the patients operated on according to the sling procedure in the long term. PMID- 8370488 TI - [Changes in central hemodynamics and peripheral circulation in pregnancy]. AB - Systemic blood pressure, stroke volume, systolic time intervals (measured via impedance cardiography), rheological properties of blood (hematocrit, plasma viscosity and erythrocyte aggregation) and peripheral flow conditions (measured via occlusive impedance plethysmography) were assessed longitudinally in 21 nonpregnant women and in 49 patients from 5th to 41st week of gestation and 4 to 9 days postpartum. Measurements were taken in the left lateral position. The data showed, that dz/dt, stroke volume and cardiac index rose until the 30th week of gestation and decreased throughout the rest of pregnancy. The same changes were observed in the data on diastolic pressure and Heather Index. Peripheral resistance fell during the first trimester and then increased notably throughout the following time of pregnancy. The systolic time intervals become longer in the last trimester of pregnancy, but were characterised by a markedly shortened left ventricular ejection time (LVET). The reduction of stroke volume in the last trimester is due to diminished venous return or venous outflow by obstruction of the inferior vena cava or by abnormalities in the left ventricular function and/or impaired rheological properties of the blood. PMID- 8370489 TI - [Correlation between reduced amniotic fluid volume and Doppler spectra of fetal blood vessels at term]. AB - The aim of this study was to determine, whether foetuses with reduced amniotic fluid in other-wise uncomplicated pregnancies at term show signs of redistribution of blood flow analogous to foetuses with intrauterine growth retardation. In 33 pregnancies > or = 37 gestational weeks with the largest pocket of amniotic fluid < 2 cm, flow velocity waveforms were recorded for the umbilical artery, middle cerebral artery and renal artery and compared with those of foetuses of the same gestational age and normal amniotic fluid volume. No difference was found in the resistance index (umbilical artery and middle cerebral artery), the pulsatility index (renal artery), or for the cerebral placental ratio between these two collectives. We conclude, that Doppler examination of foetal vessels does not help to clarify the phenomenon of decreasing amniotic fluid volume during the final period of gestation. We suggest, that the decrease is not caused by renovascular changes, but has intra- or extrarenal causes. PMID- 8370490 TI - [Atypical cytologic findings in pregnancy]. AB - The clinical significance of dysplasia and precancerous lesions of the cervix in pregnancy, frequency, age distribution and etiological factors is demonstrated based upon the clinical material of the Department of Obstetrics and Gynaecology of the University of Tubingen from 1970 to 1984. The diagnostic and therapeutic guidelines (cytology, colposcopy, histology by biopsy, conisation or hysterectomy) during pregnancy and associated problems are presented in detail. From a total of 168 patients included in the study, 128 revealed the histological classification Pap III/IIID, 38 Pap IVa/b and 2 cases Pap V. Histological carcinoma in situ was verified in 16 cases, microinvasive carcinoma in 6 cases and in 4 cases invasive cancer. From the data obtained, the following conclusions can be drawn: 1. Many of the dysplastic lesions of the cervix in pregnancy are found accidentally because of the limited participation of the patients in the routine cancer screening programme. 2. The precancerous lesions, even unfavourable stages, increase markedly in pregnancy. There is a shift towards younger women. 3. The known risk factors for cervical pre-invasive and invasive cervical abnormalities are confirmed. 4. For the management of cervical dysplasia in pregnancy it could be concluded, that observation by cytology and colposcopy should be done in cases with Pap III/IIID. In cases with Pap IVa/b, careful observation is mandatory, also by biopsy. Doubtful findings require conisation. Generally, this is also possible in pregnancy without complications. If invasion is excluded, an observant attitude may be adopted until delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8370491 TI - [Clarithromycin, a new macrolide antibiotic. Effectiveness in puerperal infections and pharmacokinetics in breast milk]. AB - The aims of this study were, to determine the pharmacokinetic parameters of clarithromycin and to study the passage of the drug into breast milk. Twelve patients (age 24 to 38; weight 44 to 83 kg), suffering from puerperal infections, were treated orally with 250 mg clarithromycin b.i.d. for 6 days. Samples of blood and breast milk were taken at timed intervals. The specimens were assayed for clarithromycin and its active metabolite 14-hydroxy-clarithromycin by HPLC and electrochemical detection. Serum concentrations of clarithromycin in the investigated patients were higher than those reported in healthy volunteers. The mean peak concentrations of clarithromycin and 14-hydroxy-clarithromycin in breast milk were about 25%, and 75% respectively of the corresponding serum concentrations. All patients recovered within 2 to 4 days and no drug-associated side effects (eg. gastrointestinal) were noted. Clarithromycin appears to be an appropriate antibiotic for the treatment of puerperal infections and (because of its considerable concentrations in breast milk) for puerperal mastitis as well. PMID- 8370492 TI - [CA-125--a tumor marker of lymphangioleiomyomatosis of diagnostic and prognostic importance?]. AB - Lymphangioleiomyomatosis is a rare tumour of the lymphatic system, affecting mostly women of childbearing age. Due to its rare occurrence, diagnosis is mostly made after thorough examination therefore time for an early treatment is lost. Diagnostically important are, on the one hand, the histological findings with smooth muscle cells invading the lymphatic system, and on the other hand thin walled cysts in CT scanning of the lung. CA-125 seems to be a suitable screening parameter for LAM, which may be additionally of prognostic value. Sensitivity and specificity of CA-125 require further observation. PMID- 8370493 TI - [Choriocarcinoma of the uterine cervix and cervical pregnancy]. AB - Case report of a 20-year-old women with a chorionic carcinoma of the uterine cervix. Subsequently, the aspects of the disease of chorionic carcinoma and cervical pregnancy are discussed, including epidemiology, aetiology, diagnosis and management. Finally, the conclusions of this discussion are compared with the case report. PMID- 8370494 TI - [Why are most children born from I. cephalic presentation?]. AB - The question, why most children are delivered in I. cephalic position, is unsolved up to now. Most children are positioned with crossed legs in the uterus. Ultrasonography was employed from the 36th week of gestation onwards to find out whether there is a connection between crossing of the legs and the position in utero. From 58 pregnancies with I. position in 47 cases and from 32 pregnancies with II. position in 28 cases, the leg nearer to the back of the mother was crossed over the other one. According to the neuro-cerebral differentiation between both sides, the foetus prefers a crossing in such a manner, that the left leg is folded over the right leg. The foetus finds a more stable position, if the more mobile leg is directed with the foot against the yielding belly walls of the mother. In accordance with the preferred crossing of the left leg over the right leg the I. position in utero is more frequent. PMID- 8370495 TI - [Gestagen-estrogen combinations in gynecology. On the history, dosage and use of a hormone principle]. AB - The first experimental and clinical investigations with gestagen-oestrogen combinations were undertaken in the late 'forties and the early' fifties of this century. In the course of further research and development, the dosage and mixture ratio of this hormonal principle were adjusted, according to the physiological status of the corpus luteum phase and its imitation by means of administration of hormonal doses. Considering the relatively large individual variations, an average daily production of 0.05 mg oestradiol/oestrone and 25 mg progesterone can be assumed, the mixture ratio being 1:50. Further indicators for the dosage were obtained by studying the biological valency of the semi-synthetic substances on the basis of the following parameters: transformation dose, menstruation delay test, anti-oestrogenic effectiveness and ovulation inhibition dose. Finally, dosage was also determined by the relevant indications; in this respect, depending on the intended use, preparations with the emphasis either on the oestrogen component or the gestagen component were deliberately produced. Up to the end of the 'fifties', parenteral gestagen-oestrogen combinations were the only preparations available for gynaecological hormonal therapy. Oral medication was predominant from 1957 onwards. The high ranking achieved by the combination preparations was due to their properties with respect to regulating menstrual haemorrhage and inhibiting proliferation and ovulation, as well as to their antiandrogenic properties. As far as methods of application were concerned, cyclical administration was most frequently employed (including phase variants), therapeutic amenorrhoea being second, whereas high-dosage application in the sense of hormonal pseudopregnancy was less often used. The gestagen-oestrogen combinations have become the most important hormonal principle in gynaecology as therapeutic agents and hormonal contraceptives. PMID- 8370496 TI - [Use of molecular genetic diagnosis of malignant hyperthermic syndrome (MHS) in selection of pigs]. AB - Recently, a mutation has been discovered in the ryanodine-receptor gene causing malignant hyperthermic syndrome (MHS) in pigs. Taking advantage of the RCR analysis of tissue samples from pigs of the Deutch Landeras breed we could have demonstrated that the gene-diagnostics MHS analysis is a simple, reliable and significant way of gene-typing for the stress resistance. Employing this test with sufficient reliability and effectively will make it possible to create homozygous stress resistant lines and to produce heterozygous stress resistant animals having both good meat quality tending to improvement and good feeding characters. The advantages of this first gene--technological technique just ready for application in animal breeding seem to ensure its quick implementation into the applied pig breeding. PMID- 8370497 TI - [Behavior of pachytene chromosomes in male mice heterozygotic for various translocations (Rb(8,17), T(16,17)43H)]. AB - The electron microscopic analysis of synaptonemal complexes of the Robertsonian translocation heterozygotes (Rb/T) and heterozygotes of the reciprocal translocation (Rb(8, 17)/T(16, 17) 43H revealed three types of translocation configurations (TC). The observed TC were subdivided into three types according to the manner of synapsis: 1) full synapsis of homologues forming trivalent with interstitial centromere in 15%; 2) the centromeric asynapsis (8 and 17-16 chromosomes forming trivalent with the extension region of asynapsis and breakpoint of the reciprocal translocation on chromosome 17 in 70%; 3) centromeric asynapsis (only single chromosome 17-16 of trivalent, when the break point of reciprocal translocation and the absence of centromeric asynapsis of another chromosome 8 formed trivalent in 15%). The frequency of association between trivalents and the XY bivalents is 20% and close proximity is 15% for heterozygotes Rb/T. Which are fertile, while in the sterile heterozygotes Rb(8, 17)/T(16, 17) 43H it is 45% for association and 15% close proximity (total 60%). These data show the significant differences in the contact of translocation configurations with the XY bivalents of fertile heterozygotes, in comparison with the sterile. Thus, it is shown that the chromosome pairing of fertile and sterile mice is clearly distinguished. PMID- 8370498 TI - [Molecular diagnosis of fragile X-chromosome syndrome (Martin-Bell syndrome) in patients of native populations]. AB - 63 families at-rist of Fragile X-syndrome (FraX) are subjected to Southern blot analysis with the DNA probes Ox1.9 and Ox0.55. Molecular studies have confirmed an initial clinical diagnosis of FraX in 26 families earlier studied cytogenetically and in 11 of 27 families with only some clinical traits of FraX syndrome in proband. Full mutation and premutation condition of FMR-1 gene was ascertained in 34 and rejected in 18 close relatives of probands with the proved FraX syndrome in 37 and families. Four different patterns of pathological alleles are detected at electrophoretograms of DNA samples restricted by endonuclease RcoRI and hybridized to the DNA probe Ox1.9. Prenatal diagnosis of FraX was carried out in two cases at the 1st and 2nd trimester of pregnancy. Perspective of broad application of molecular methods for early diagnostics and prophylactic of FraX syndrome are briefly discussed. PMID- 8370499 TI - [Migration structure and inbreeding in the Talysh population]. AB - The origin of genes in Talysh population (South Azerbaijan Republic) is considered. During 11 generations of population history more than 100 unrelated persons supplied the genes to the population. At present, the population is highly isolated: the endogamy index is 0.878, gametic index being 0.935. Inbreeding is estimated both ty means of genealogy and from the frequency of marriages between the persons of the same kin. The inbreeding coefficient is FIT = 0.026-0.030, its random component is FST = 0.01-0.02 and non-random component is FIS = 0.026-0.020. PMID- 8370500 TI - [Load of autosomal recessive diseases in populations of Kirov Province and its relationship to consanguinity]. AB - The dependence of the load of autosomal recessive disorders on a variation of random inbreeding in the populations of the 9th Districts of the Kirov Province was investigated. The values of the Fst varied between different districts from 0.00021 to 0.0011 and the values of load of AR--from 0.73 to 2.01 affected per 1000. There is a close significant correlation (r = 0.90) between the parameters in the population studied which increased under analysis of the population considering the coefficients of random inbreeding. PMID- 8370501 TI - [Computer program of genetic map construction and database of gene localization]. AB - Computer data base containing information about gene localization in the chromosomes of various organisms is composed. Computer program of genetic map constructing is created. The program represents graphically the information conserving in the data base. The data base and the program are intended for realization on the IBM-compatible computers. PMID- 8370502 TI - [Amplification of the integrated bovine growth hormone transgene using the polymerase chain reaction (PCR)]. AB - Conditions of the PCR amplification of unique fragments of bovine growth hormone (bGH) were found that allow reliable identification of transgenic rabbits for this gene. An integrated construction containing a part of MT promoter of metallothionein gene and chromosomal bGH gene was amplified. Two of 46 newborn lambs were found to be transgenic for the bGH gene by using primers BG3 and BG4 for amplification of the gene bGH fragment and its following restriction with pVUII. We managed to whow the possibility of successful amplification of growth hormones genes of pig and sheep using primers BG3 and BG8, corresponding respectively to the beginning and the end of the bGH gene. PMID- 8370503 TI - [Cloning of recA and lexA genes on the plasmid with a broad host range]. AB - The recA gene from Escherichia coli and Propionibacterium shermanii and lexA gene from E. coli were cloned of the plasmid pBI101 with a broad host range. The correlation of induction of the SOS function and the dose of UV-light, MMS and 4 NQO was studied in E. coli cells carrying the plasmid pJE43. The level of SOS response in recA cells carrying the plasmid pBI101::recA E. coli and pBI101::recA P. shermanii was higher than a SOS response level in EC1000 with a normal recA gene. However, no complete complementation of the SOS function was observed in recA cells when pBI101 with recA and lexA genes was incorporated and under the action of all mutagenic factors. PMID- 8370505 TI - [Genetic analysis of differences in dopamine metabolism in two Drosophila virilis lines under normal conditions and under heat stress]. AB - The results of genetic analysis of the differences in dopamine (DA) content between two lines of Drosophila virilis in response to heat stress are presented. The gene(s) controlling the differences in DA content under normal conditions is located on the X-chromosome, and the gene(s) controlling the differences in responsiveness of DA system to stress was found to be autosomal. By means of polyacrylamide gel electrophoresis was also examined phenoloxidase activity in these lines under normal conditions and short-term heat stress (60 min, 38 degrees C). Of the five phenol oxidase fractions identified, three were major, A1, A2 and A3 components, and two appeared occasionally. It seems likely that A1 is monophenol oxidase and A2 is diphenol oxidase. It was shown that neither mono, nor diphenol oxidase activities change under heat stress. It was found that D. virilis lines 147 and 101 differ in diphenol oxidase activity under normal conditions. Genetic analysis of these differences revealed that they are controlled by a single gene (or a group of closely linked genes). The gene controlling diphenol oxidase activity in D. virilis is located on the X chromosome. PMID- 8370504 TI - [Cloning of the RIB7 gene encoding the riboflavin synthase of the yeast Pichia guilliermondii]. AB - The RIB7 gene encoding the enzyme of the final stage of riboflavin biosynthesis in Pichia guilliermondii--riboflavin synthase was cloned on the pFL38 shuttle vector as the Sau3A fragment of the chromosomal DNA of about 4 kb. The HindIII fragment of 1.4 kb was subcloned from the hybrid plasmid pFR7 obtained onto the pUC18 plasmid. The plasmid pR7 thus constructed transform Escherichia coli ribB 45 mutant cells with a blocked riboflavin synthase approximately at the same frequency as pFR7. High riboflavin synthase activity was discovered in the E. coli transformants carrying pR7 but not pFR7. Using both plasmids we also complemented rib17 mutant of P. guilliermondii. PMID- 8370506 TI - [Sex chromosome behavior in meiosis in the gray hamster (Cricetulus migratorius Pallas, 1770)]. AB - The sequence of X and Y chromosomes pairing at meiotic prophase in the Armenian hamster Cricetulus migratorius Pall., 1770 gas been studied. The results of differential staining (C-, Ag-NOR) of mitotic chromosomes are presented. The rare case of interstitial synapsis of the sex chromosomes has been described. Earlier it was established only for Peromyscus sitkensis (Hale, Greenbaum, 1986). Pairing of the X and Y chromosomes is initiated at an interstitial position of the euchromatic region with subsequent synapsis towards the telomeres of the short arms. The latter conjugate completely and in this state do not differ outwardly from autosomal bivalents. The long arms remain asynaptic (heteropycnotic) constantly but at the meiosis undergo different morphological changes (thickness, bulging, clear showing filament structures, etc.) The data obtained agree with the hypothesis of Matthey (1961) claiming that the paired parts of X and Y chromosomes of the species with large Y chromosome and visible chiasma have autosomal origin. Therefore, X and Y chromosomes of Cricetulus migratorius could be originated via autosome-gonosome translocation. PMID- 8370507 TI - [Some developmental features of Escherichia coli Mu phage in Pseudomonas aeruginosa cells]. AB - In order to determine the replication-transposition (RT) efficiency of Escherichia coli phage Mu in Pseudomonas aeruginosa cells, the change of Mu DNA copy number after transfer of P. aeruginosa (RP4::Mu) from 42 (the condition of RP4::Mu plasmid stability and low phage production level in P. aeruginosa) to 30 degrees C (the condition of RP4::Mu plasmid instability and higher phage production level in P. aeruginosa) was analysed. It was shown that the temperature shift causes no increase in Mu DNA copy number, although free phage DNA is revealed after transfer of the cells at 30 degrees C. Considering that the studied cells contained also a linear RP4 DNA and the free Mu DNA hybridized with the RP4 DNA, we proposed that the mature Mu DNA arises as a result of Mu genome packaging from the original plasmid. So, the Mu genome RT is uneffective in P. aeruginosa and all of the phage particles released from P. aeruginosa (RP4::Mu) cells contain Mu DNA apparently originated from the DNA of hybrid plasmid RP4::Mu. Moreover, these results suggest that the Mu DNA packaging is not effective in P. aeruginosa (taking into account that the P. aeruginosa (RP4::Mu) cells release about 10(-2) p.f.u./cell and that originally the copy number of RP4::Mu > or = 1). PMID- 8370508 TI - [Number of chromosome breaks and the probability of break reunion during irradiation of mature Drosophila sperm]. AB - The dose-effect curves for half and full translocations induced in mature sperm with the break points within the same chromosomal region were obtained. Probability of reunion q and the number of breaks N that could be calculated from these curves varies within the range 0.83-0.69 and 0.011-0.078, respectively. The half and full translocations were induced under maternal effect of mus 104D1. In this case, q = 0.86 (for normal genotype 0.79) and N = 0.114 (for normal genotype 0.048). These figures show that the dose increase and the introduction of the mus 104 cause increase in the breaks number and only weak change in break reunion occurs. The method developed can be used for the search for mutations that interfere with break reunion. PMID- 8370509 TI - [Effect of vitamin C on prostatilen mutagenicity in mice]. AB - Frequencies of sperm head anomalies (SHA) and chromosome aberrations (CA) in bone marrow cells were studied after injection of drugs, prostatilen and vitamin C into the male mice Mus musculus. It was found that prostatilen (5, 10 and 50 mkg) increased the frequency of both SHA and CA. Vitamin C (14 and 140 mkg) induced no CA but increased SHA frequency at the dose of 140 mkg. The joint action of the drugs led to decrease in SHA frequency for all dose combinations. Antimutagenic action of vitamin C in the CA test was recorded for only 14 mkg dose. PMID- 8370510 TI - [Genetic effects of tritium-labeled amino acids in mice]. AB - The frequency of dominant lethal mutations (DLM) in germ cells and the frequency of reciprocal translocations (RT) in spermatogonia of male mice exposed to H labeled amino acids at the dose of 1.45-2.30 Gy was studied. The effect from H glycine was equal to that from tritium oxide (THO). When D,L-lysine-3H and L lysine-3H were injected into the body of mice the frequency of DLM exceeded that from the equal dose of THO by 2.5 and 7 times, respectively. As to RT, these indexes for H-amino acids have no statistically significant differences from the similar index for THO. PMID- 8370511 TI - [Mutations in mouse minisatellite DNA, induced by radiation]. AB - Male (101/HY x C3H/SnY) F1-hybrid mice were given an acute exposure to 0.5 or 1 Gy gamma-irradiation using 60Co, and DNA fingerprints were produced from parents and progeny using probes 33.6 and 33.15. The frequency of mutations in the offspring of irradiated males was 1.72 times higher than in offspring of nonirradiated males. Possible implications of the DNA fingerprint technique in monitoring of mutations in human populations are discussed. PMID- 8370512 TI - Divergence of two families of repeated DNA in wood and field mice of the genus Apodemus (Muridae, Rodentia). AB - The nDNA of six species of a wood and field mice of the genus Apodemus (2n = 48): peninsulae, sylvaticus, flavicollis, microps, speciosus, agrarius, grey rat Rattus norvegicus as well, and house mouse Mus musculus were studied using EcoRI and HindIII restriction endonucleases with an agarose and polyacrylamide gel electrophoresis and a microdensitometry. It is shown for dispersed sequences that a quarter of 1.85 kb EcoRI genus specific family of repeated DNA is constant but a quarter of 1.35 kb EcoRI repeats, which are specific for more large taxon unit, is variable. The HindIII satDNA of the various species differs in the length of monomer, size of more representative multimer and digestion of the monomers by the same endonuclease of restriction; HindIII satDNA quantity correlates with 1.35 kb EcoRI repeat content. Some nonidentified components are found in Apodemus genomes. The possible ways evaluation of the repetitive DNA are briefly discussed. It was supposed that the evolutionary age of the wood mice is directly proportional to the length of HindIII multimer and inversely proportional to the amount of HIndIII satDNA with a 1.35 kb EcoRI repeats. PMID- 8370513 TI - [Differentiation of GC-rich restriction sites in the highly repeated DNA in Apodemus (Muridae, Rodentia]. AB - nDNAs of six species of wood and field mice of the genus Apodemus (peninsulae, flavicolis, microps, speciosus, and agrarius), grey rat Rattus norvegicus as well, and house mouse Mus musculus were digested with restriction endonucleases (MspI (CCGG), BspRI (GGCC) and MvaI (CCA/TGG). Two highly representative satellites are found in A.peninsulae (8%) and M.musculus (20%) genomes using BspRI and MvaI. The length of restriction fragments of these components are equal to n x 30 and n x 230 nb, respectively. Based on the results of PDRF of nDNA in rodent interspecies, genetic distances are estimated and phylogenetic tree reconstructed. Among wood mice examined A.sylvaticus and A.flavicollos are most closely related, A.peninsulae is more diverged. Field mouse has approx. equal differences from the european and asian species of wood mice. A middle value of genetic distances is about 7.12% in Apodemus genus, 12.69 and 13.2% between Apodemus with M.musculus and R.norvegicus, respectively. PMID- 8370514 TI - [Mapping of the dominant gene of hyperkeratosis palmaris et plantaris in man]. AB - Analysis of linkage between the gene of autosomal dominant tylosis and some loci with RFLP in 1, 14 and 17 chromosomes in the pedigree with this disorder was performed. A positive load score (0.729 at 0-0.20) for tylosis and D17S14 locus (DNA probe pTHH-59) was found. PMID- 8370515 TI - [Structure and variability of hereditary disease in the Kirov Province]. AB - The main purpose of this report is to present the nosological spectrum of hereditary diseases in 9 Districts of Kirov Province and to compare it with that studies earlier in other Russian populations. This comparison is undertaken in an attempt to define a "nucleus" of hereditary diseases in the Russian population studied. During this study 343 families with 546 affected were registered. The spectrum covered 55 different autosomal dominant, 14 autosomal recessive and 11 X linked recessive hereditary disorders in the population under study. Some of these forms could be considered as common forms for the whole Russian population, because they were met in all Russian populations which were analysed. This conclusion is proved by the cluster analysis of genetic distances calculated on the basis of gene frequencies for autosomal recessive hereditary disorders. PMID- 8370516 TI - [Role of the homologous translocation, located on the Y-chromosome, in mutagenesis of the double super-unstable system in Drosophila melanogaster males]. AB - Main features of mutagenesis induced in the double super-unstable system in Drosophila melanogaster males and females was studied earlier. Very different y- and sc-alleles arose under the mutagenesis. These are differed one from another by the expression of yellow and scute loci. However, it was shown that the female's mutagenesis very differed from the male's one. The structure of a homologous chromosome has played an important role in the mutagenesis in Drosophila females. We found here that the homologous translocation in Y chromosome led to double decrease of the frequency of the mutagenesis in males. It is proposed that interconnections between two homologous insertions are essential in the recombinational processes by which alleles change. The nature and mechanism of the sub-lethal allele's formation in the presence of translocation in Y chromosome is discussed. PMID- 8370517 TI - Spatial restriction of cellular differentiation. AB - Myxococcus xanthus cells differentiate into myxospores within a fruiting body, an aggregate of approximately 10(5) cells. Previous work had discerned an inner and outer domain within the fruiting body differentiated by cell density and cell alignment. To test whether the two domains might play different roles in spore differentiation, developmentally regulated gene fusions were screened for expression restricted to one domain or the other. Transcriptional lacZ fusions to 80 developmentally regulated genes were examined and eight fusions were found that restricted expression to the inner domain, while one fusion, omega 7621, showed initial expression in the outer domain. Initial omega 7621 expression coincided with patches of spore precursors evident in bright-field microscopy. Later in development, both omega 7621 expression and the patches expanded inward, eventually filling both the inner and outer domains. Previous work had also shown that high cell density and cell alignment are required for transmission of the C signal, which is needed to initiate spore differentiation. Evidence is presented for a novel morphogenetic mechanism in which C-signaling in the outer (high density) domain initiates spore differentiation. It is proposed that spore precursors are passively transported from the outer to the inner domain by the movements of undifferentiated rod cells. Reconstruction experiments showed that developing rod cells move with sufficient force to displace spores. Spore precursors thus accumulate in the inner domain where they express spore-specific genes at high levels and account for inner domain specific expression. PMID- 8370518 TI - Expression of a retinoblastoma transgene results in dwarf mice. AB - Introduction of the normal retinoblastoma gene (RB) into different tumor cells possessing inactivated RB genes suppresses their tumorigenicity in nude mice. These results suggest that RB replacement is a potential strategy for developing future clinical treatments of cancer. In a transgenic mouse model, we found that the quantity of RB protein in a given cell may play an important role in dictating its effect. Four founder mice containing 1-7 copies of a human RB cDNA transgene under the transcriptional control of the human RB promoter were generated. Most of the transgenic mice were smaller than nontransgenic littermates. This effect was found as early as embryonic day 15. The degree of dwarfism correlated roughly with the copy number of the transgene and the corresponding level of RB protein. The expression pattern of the transgene products was similar to that of the endogenous mouse RB gene with regard to tissue and temporal distribution. Transferring the transgene to RB deficient mice, which are nonviable, resulted in the development of normal, healthy mice, indicating that the human RB gene can functionally complement the mouse homolog. These studies demonstrate that the effect of RB on overall mouse development is closely dependent upon its dosage. PMID- 8370519 TI - Identification of a novel zinc finger protein binding a conserved element critical for Pit-1-dependent growth hormone gene expression. AB - The growth hormone (GH) and prolactin genes require the pituitary-specific POU domain transcription factor Pit-1 for their activation. However, additional factors are necessary for the effective expression of these genes. Analysis of evolutionarily conserved sequences in the proximal GH promoter suggests the critical importance of one highly conserved element located between the two Pit-1 response elements. Mutation of this site decreases expression of a transgene in mice > 100-fold. We have identified a major activity binding to this site as a novel member of the Cys/His zinc finger superfamily, referred to as Zn-15. The Zn 15 DNA-binding domain comprises three zinc fingers separated by unusually long linker sequences that would be expected to interrupt specific DNA site recognition. Zn-15 synergizes with Pit-1 to activate the GH promoter in heterologous cell lines in which this promoter is only minimally responsive to Pit-1 alone. Our data suggest that functional interactions between the tissue specific POU domain factor Pit-1 and this novel zinc finger factor binding to an evolutionarily conserved region in the GH promoter may constitute an important component of the combinatorial code that underlies the effective expression of the GH gene. PMID- 8370520 TI - A bZIP protein, sisterless-a, collaborates with bHLH transcription factors early in Drosophila development to determine sex. AB - Sexual identity in Drosophila is determined by zygotic X-chromosome dose. Two potent indicators of X-chromosome dose are sisterless-a (sis-a) and sisterless-b (sis-b). Genetic analysis has shown that a diplo-X dose of these genes activates their regulatory target, the feminizing switch gene Sex-lethal (Sxl), whereas a haplo-X dose leaves Sxl inactive. sis-b encodes a transcriptional activator of the bHLH family that dimerizes with several other HLH proteins required for the proper assessment of X dose. Here, we report that sis-a encodes a bZIP protein homolog that functions in all somatic nuclei to activate Sxl transcription. In contrast with other elements of the sex-determination signal, the functioning of this transcription factor in somatic cells may be specific to X-chromosome counting. Using in situ hybridization, we determined the time course of sis-a, sis-b, and Sxl transcription during the first few hours after fertilization. The pattern of sis-a RNA accumulation is very similar to that for sis-b, with a peak in nuclear cycle 12 at about the time of onset of Sxl transcription. Considered in the context of other studies, these results suggest that the ability to distinguish one X from two is attributable to combinatorial interactions between bZIP and bHLH proteins and their target, Sxl, as well as to positive and negative interactions with maternally supplied and zygotically produced proteins. PMID- 8370521 TI - Interactions between dorsal and helix-loop-helix proteins initiate the differentiation of the embryonic mesoderm and neuroectoderm in Drosophila. AB - The dorsal (dl) morphogen has been implicated in the establishment of the embryonic mesoderm, neuroectoderm, and dorsal ectoderm in Drosophila. Here we show that the simultaneous reduction in the levels of dl and any one of several helix-loop-helix (HLH) proteins results in severe disruptions in the formation of mesoderm and neuroectoderm. Certain triple heterozygous combinations essentially lack mesoderm as a result of a block in ventral furrow formation during gastrulation. HLH proteins that have been implicated previously in sex determination and neurogenesis (daughterless, achaete, and scute) are shown to be required for the formation of these embryonic tissues. Evidence is also presented that dl-HLH interactions involve the direct physical association of these proteins in solution mediated by the rel and HLH domains. We discuss the striking parallels in mesoderm formation and sex determination. PMID- 8370522 TI - Masking mRNA from translation in somatic cells. AB - We present evidence for a role for Y-box proteins in both mRNA transcription and translation. We have expressed an oocyte-specific RNA-binding protein (FRGY2) in somatic cells. This protein is normally found together with mRNA in large amounts within the masked maternal mRNA storage particles of Xenopus laevis oocytes. Masked maternal mRNA is believed to be translationally repressed during oogenesis and is stored within ribonucleoprotein storage particles for subsequent use during embryogenesis. Surprisingly, FRGY2 is not only found to direct the accumulation of mRNA from promoters containing binding sites for the protein but also to selectively repress translation of the same mRNA. Thus, the role of FRGY2 in the transcription and storage of maternal mRNA is similar to that of the transcription factor TFIIIA in the transcription and storage of 5S rRNA from the oocyte type 5S rRNA genes. PMID- 8370523 TI - mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor. AB - Nonsense mutations in a gene can accelerate the decay rate of the mRNA transcribed from that gene, a phenomenon we describe as nonsense-mediated mRNA decay. Using amber (UAG) mutants of the yeast PGK1 gene as a model system, we find that nonsense-mediated mRNA decay is position dependent, that is, nonsense mutations within the initial two-thirds of the PGK1-coding region accelerate the decay rate of the PGK1 transcript < or = 12-fold, whereas nonsense mutations within the carboxy-terminal third of the coding region have no effect on mRNA decay. Moreover, we find that this position effect reflects (1) a requirement for sequences 3' to the nonsense mutation that may be necessary for translational reinitiation or pausing, and (2) the presence of an additional sequence that, when translated, inactivates the nonsense-mediated mRNA decay pathway. This stabilizing element is positioned within the coding region such that it constitutes the boundary between nonsense mutations that do or do not affect mRNA decay. Rapid decay of PGK1 nonsense-containing transcripts is also dependent on the status of the UPF1 gene. Regardless of the position of an amber codon in the PGK1 gene, deletion of the UPF1 gene restores wild-type decay rates to nonsense containing PGK1 transcripts. PMID- 8370524 TI - Dominant negative alleles of RAD52 reveal a DNA repair/recombination complex including Rad51 and Rad52. AB - Saccharomyces cerevisiae rad52 mutants are characterized by severe defects in double-strand break (DSB) repair and recombination. In this study we have identified several regions of RAD52 that are required for these biological functions. We cloned and characterized a RAD52 homolog from Kluyveromyces lactis that partially complemented S. cerevisiae rad52 mutants while exhibiting negative dominance in wild-type (RAD52) strains. The dominant negative effect was suppressed by overexpression of RAD51, an additional gene known to be required for DSB repair and recombination, indicating a genetic interaction between these loci. Furthermore, GAL4 two-hybrid analysis revealed a physical interaction between Rad51 and the carboxy-terminal one-third of Rad52. Deletion alleles of rad52 (with or without the Rad51 association domain) also produced dominant negative defects, suggesting the disruption of repair through nonfunctional interactions with other DSB repair and recombination proteins. RAD51 relieved the negative dominance of each of these alleles either by competitive titration or functional activation of mutant or heterologous Rad52 proteins. These results demonstrate the importance of Rad52-Rad51 interactions and point to the formation of a higher order repair/recombination complex potentially containing other yet unidentified components. PMID- 8370525 TI - Transcription-dependent recombination induced by triple-helix formation. AB - The homologous recombination between direct repeat sequences separated by either 200 or 1000 bp was induced by active transcription of the downstream gene when poly(dG)-poly(dC) sequences exist between the two direct repeats. This dG tract mediated and transcription-induced recombination was RecA independent, and the frequency of recombination was dependent on both the length and the orientation of the poly(dG)-poly(dC) sequences relative to the gene. An intramolecular dG.dG.dC triplex formation was detected in Escherichia coli cells in a length dependent manner when the transcription of the downstream gene was activated. We suggest that the negative superhelical strain generated by active transcription of the downstream gene induces poly(dG)-poly(dC) sequences to adopt a triple helix structure in vivo and that this structure brings two remote sequences together to stimulate homologous recombination. PMID- 8370526 TI - Potentiation of RNA polymerase II transcription by Gal4-VP16 during but not after DNA replication and chromatin assembly. AB - Purified, reconstituted chromatin templates containing regular, physiological nucleosome spacing were transcribed in vitro by RNA polymerase II along with the Gal4-VP16 activator. When Gal4-VP16 was prebound to DNA before reconstitution of either H1-deficient or H1-containing chromatin, the resulting templates were transcribed with a similar efficiency. Under such conditions, we observed long range (1000 bp) activation of transcription in vitro with H1-containing chromatin, but not naked DNA templates. When Gal4-VP16 was added to preassembled chromatin, the H1-deficient chromatin was transcriptionally active, whereas the H1-containing chromatin, which possessed properties similar to native chromatin, was transcriptionally inert. We then mimicked DNA replication and chromatin assembly at a replication fork and found that Gal4-VP16 could potentiate transcription during, but not after, replication and assembly of histone H1 containing chromatin. These experiments provide biochemical data that support a DNA replication-dependent mechanism for reconfiguration of chromatin structure and activation of transcription by Gal4-VP16. PMID- 8370527 TI - The erythroid protein cGATA-1 functions with a stage-specific factor to activate transcription of chromatin-assembled beta-globin genes. AB - The chick beta-globin gene is regulated developmentally within erythroid cells by the interaction of multiple proteins with the promoter and the 3' enhancer. These interactions are correlated with changes in chromatin structure, which are characteristic of the actively expressed gene. Using in vitro chromatin assembly and transcription with staged erythroid extracts, we have determined the critical proteins required to activate expression of nucleosome-reconstituted beta-globin genes. These genes contain a specialized TATA box at -30 (GATA) through which the erythroid-restricted protein cGATA-1 and TFIID both function to regulate different steps in beta-globin expression. We find that TBP (TATA-binding protein) alone can activate transcription of beta-globin chromatin templates from promoters mutated to a canonical TATA box but is ineffective on those containing the normal -30 GATA site. The occupancy of this site by cGATA-1 also fails to generate efficient expression of beta-globin chromatin unless combined with a stage-specific protein, NF-E4, that binds to an adjacent site. However, NF-E4 does not function with TBP to derepress nucleosome-assembled beta-globin genes. We propose that the developmental regulation of beta-globin expression is achieved, in part, by the requirement of an erythroid protein and a stage specific factor, rather than TBP, to activate chromatin through a specialized TATA box. PMID- 8370528 TI - Functional interaction of adenovirus E1A with holo-TFIID. AB - The activation domains of several regulatory transcription factors have been shown to bind directly in vitro to the TATA box-binding protein (TBP). Yet TBP must also interact with multiple associated polypeptides, called TAFs, for these same activators to stimulate transcription. These findings raise the question of how TBP can interact with so many proteins, both activators and TAFs, simultaneously. Here, we show that the activation domain of the adenovirus large E1A protein can bind specifically and stably to isolated holo-TFIID, the multisubunit protein complex consisting of TBP plus TAFs. Consequently, the surface of TBP that interacts with E1A must be exposed in the holo-TFIID complex. To assess the functional significance of this interaction, we established an in vitro transcription system responsive to the E1A activation domain. The addition of excess E1A to this system inhibits (squelches) both E1A-dependent and E1A independent transcription by sequestering a target factor required for E1A activation. From among the component activities that collectively reconstitute E1A-responsive transcription in this system, holo-TFIID alone is singularly capable of reversing the inhibition of transcription mediated by excess E1A, indicating that holo-TFIID is the direct functional target of the E1A activation domain. PMID- 8370529 TI - Rapid transcriptional autoregulation of a yeast metalloregulatory transcription factor is essential for high-level copper detoxification. AB - Copper detoxification in the yeast Candida glabrata is carried out in large part by a family of metallothionein (MT) genes: a unique MT-I gene, a tandemly amplified MT-IIa gene, and a single unlinked MT-IIb gene. In response to elevated environmental copper levels, members of this MT gene family are transcriptionally activated by a copper-dependent, sequence-specific DNA-binding transcription factor, AMT1. AMT1 shares several structural and functional features with the Saccharomyces cerevisiae copper metalloregulatory transcription factor ACE1, which is constitutively expressed and poised for rapid transcriptional responses to the toxic metal copper. In this paper, we demonstrate that AMT1 is subject to positive transcriptional autoregulation, which is exerted through binding of copper-activated AMT1 to a single copper responsive element in the AMT1 promoter. A nonautoregulatory amt1 mutant displayed a marked decrease in both copper tolerance and expression of the MT-II genes, which are critical for high-level copper detoxification in Candida glabrata. Kinetic analysis demonstrated the remarkably rapid AMT1 mRNA accumulation in the presence of copper, which is followed by increased expression of the metallothionein gene products. These results demonstrate that AMT1-positive autoregulation plays a critical role in metal detoxification and suggest that the rapid autoactivation of the AMT1 metalloregulatory transcription factor biosynthesis is essential for C. glabrata to quickly build up a cellular defense line to protect cells upon exposure to high environmental copper levels.